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13,500 | 18,663,107 | Results indicated that AAC interventions do not impede speech production .
In fact , most studies reported an increase in speech production .
However , in-depth analyses revealed that the gains were rather modest . | PURPOSE This systematic review aim ed to determine the effects of augmentative and alternative communication ( AAC ) intervention on speech production in children with autism or pervasive developmental disorder-not otherwise specified . | PURPOSE This r and omized group experiment compared the efficacy of 2 communication interventions ( Responsive Education and Prelinguistic Milieu Teaching [ RPMT ] and the Picture Exchange Communication System [ PECS ] ) on spoken communication in 36 preschoolers with autism spectrum disorders ( ASD ) . METHOD Each treatment was delivered to children for a maximum total of 24 hr over a 6-month period . Spoken communication was assessed in a rigorous test of generalization at pretreatment , posttreatment , and 6-month follow-up periods . RESULTS PECS was more successful than RPMT in increasing the number of nonimitative spoken communication acts and the number of different nonimitative words used at the posttreatment period . Considering growth over all 3 measurement periods , an exploratory analysis showed that growth rate of the number of different nonimitative words was faster in the PECS group than in the RPMT group for children who began treatment with relatively high object exploration . In contrast , analogous slopes were steeper in the RPMT group than in the PECS group for children who began treatment with relatively low object exploration The context for this work was an evaluation study [ Carr , D. , & Felce , J. A. ( in press ) ] of the early phases of the Picture Exchange Communication System ( PECS ) [ Frost , L. A. , & Bondy , A. S. ( 1994 ) . The picture exchange communication system training manual . Cherry Hill , NJ : Pyramid Educational Consultants , Inc. ; Frost , L. A. , & Bondy , A. S. ( 2004 ) . The picture exchange communication system training manual , 2nd edn . Newark , DE : Pyramid Educational Consultants , Inc. ] . This paper reports that five of 24 children who received 15 h of PECS teaching towards Phase III over a period of 4–5 weeks , showed concomitant increases in speech production , either in initiating communication with staff or in responding , or both . No children in the PECS group demonstrated a decrease in spoken words after receiving PECS teaching . In the control group , only one of 17 children demonstrated a minimal increase and four of 17 children demonstrated a decrease in use of spoken words after a similar period without PECS teaching The study investigated the impact of mastery of the Picture Exchange Communication System ( PECS ) to Phase III , on the communications of children with autism . Children aged between 3 and 7 years , formed a PECS intervention group and a non-intervention control group . The intervention group received 15 h of PECS teaching over 5 weeks . Three 2-h classroom observations recorded communications between the children and their teachers . These occurred : 6 weeks before teaching ; during the week immediately prior to teaching ; during the week immediately following teaching . For the control group , two 2-h observations were separated by a 5-week interval without PECS teaching . Communicative initiations and dyadic interactions increased significantly between the children and teachers in the PECS group but not for the control group OBJECTIVE To assess the effectiveness of expert training and consultancy for teachers of children with autism spectrum disorder in the use of the Picture Exchange Communication System ( PECS ) . METHOD DESIGN Group r and omised , controlled trial ( 3 groups : immediate treatment , delayed treatment , no treatment ) . PARTICIPANTS 84 elementary school children , mean age 6.8 years . TREATMENT A 2-day PECS workshop for teachers plus 6 half-day , school-based training sessions with expert consultants over 5 months . OUTCOME MEASURES Rates of : communicative initiations , use of PECS , and speech in the classroom ; Autism Diagnostic Observation Schedule-Generic ( ADOS-G ) domain scores for Communication and Reciprocal Social Interaction ; scores on formal language tests . RESULTS Controlling for baseline age , developmental quotient ( DQ ) and language ; rates of initiations and PECS usage increased significantly immediately post-treatment ( Odds Ratio ( OR ) of being in a higher ordinal rate category 2.72 , 95 % confidence interval 1.22 - 6.09 , p < .05 and OR 3.90 ( 95%CI 1.75 - 8.68 ) , p < .001 , respectively ) . There were no increases in frequency of speech , or improvements in ADOS-G ratings or language test scores . CONCLUSIONS The results indicate modest effectiveness of PECS teacher training/consultancy . Rates of pupils ' initiations and use of symbols in the classroom increased , although there was no evidence of improvement in other areas of communication . TREATMENT effects were not maintained once active intervention ceased The purpose of this study was to determine ( 1 ) whether comprehension , production , and spontaneous use of language are greater following language training by sign-alone , speech-alone , simultaneous communication , or alternating between speech and sign ; ( 2 ) whether high- and low-verbal imitators benefit from the same mode of treatment ; and ( 3 ) whether retention of the language skills differs among the four training conditions . Subjects were 60 moderate to severe autistic children r and omly assigned to one of four treatment conditions . Subjects were divided into high- and low-verbal imitators based on verbal imitation performances . The results indicated that the high-verbal imitators did equally well in all four treatment conditions , while the low-verbal imitators did poorest in the speech-alone condition . The high-verbal imitators performed better than did the low-verbal imitators in all of the treatment conditions . Words or signs learned were retained for three months after treatment regardless of the treatment condition or level of imitative ability . The results were discussed in terms of the efficacy of using sign language with autistic children This study was carried out to test the main and interaction effects of training condition and pretreatment-elicited verbal imitation ability when predicting spoken language use during language training of 60 minimally verbal autistic children . Subjects were r and omly assigned to Speech Alone , Sign Alone , Simultaneous Presentation of Sign and Speech , and Alternating Presentation of Sign and Speech training conditions . Speech Alone , Simultaneous Presentation , and Alternating Presentation condition facilitated more child-initiated speech during treatment than did the Sign Alone condition . Regardless of training condition , pretreatment verbal imitation ability positively predicted the size of child-initiated spoken vocabulary observed during training . Exploratory analyses indicated that , in addition to verbal imitation , pretreatment age and IQ may also predict spoken language developed during training |
13,501 | 19,843,620 | None of the instruments demonstrated satisfactory results for all measurement properties .
Responsiveness was not tested adequately for any of the instruments .
Very few of the studies provided information on the interpretation of the scores .
Overall , the MQOL , followed by the QUAL-E and the QODD , received the best ratings for their measurement properties . | Purpose : In this literature review we evaluated the feasibility and clinimetric quality of quality -of-life ( QoL ) measurement instruments suitable for use in palliative care . | The increasing number of palliative care patients necessitates a simple , reliable instrument to routinely measure outcomes among hospice patients . We tested the utility of the Brief Hospice Inventory ( BHI ) to assess outcomes of hospice patients and estimations of patients ' outcomes by nurse caregivers . In a prospect i ve study , 145 home-based hospice patients were enrolled in the study from VistaCare Hospice . During the first week of admission , patients and nurse caregivers completed the BHI , which assessed patients ' symptoms , satisfaction with care , and quality of life . Factor analysis supported a two-factor structure for the BHI for patients and caregivers , including a symptom subscale and quality of life subscale . Patients with severe symptoms showed improvement on the symptom subscale , but not the quality of life subscale , during the first 2 weeks after admission . The BHI shows utility in measuring hospice patients ' symptom severity and quality of life over time CONTEXT A clear underst and ing of what patients , families , and health care practitioners view as important at the end of life is integral to the success of improving care of dying patients . Empirical evidence defining such factors , however , is lacking . OBJECTIVE To determine the factors considered important at the end of life by patients , their families , physicians , and other care providers . DESIGN AND SETTING Cross-sectional , stratified r and om national survey conducted in March-August 1999 . PARTICIPANTS Seriously ill patients ( n = 340 ) , recently bereaved family ( n = 332 ) , physicians ( n = 361 ) , and other care providers ( nurses , social workers , chaplains , and hospice volunteers ; n = 429 ) . MAIN OUTCOME MEASURES Importance of 44 attributes of quality at the end of life ( 5-point scale ) and rankings of 9 major attributes , compared in the 4 groups . RESULTS Twenty-six items consistently were rated as being important ( > 70 % responding that item is important ) across all 4 groups , including pain and symptom management , preparation for death , achieving a sense of completion , decisions about treatment preferences , and being treated as a " whole person . " Eight items received strong importance ratings from patients but less from physicians ( P<.001 ) , including being mentally aware , having funeral arrangements planned , not being a burden , helping others , and coming to peace with God . Ten items had broad variation within as well as among the 4 groups , including decisions about life-sustaining treatments , dying at home , and talking about the meaning of death . Participants ranked freedom from pain most important and dying at home least important among 9 major attributes . CONCLUSIONS Although pain and symptom management , communication with one 's physician , preparation for death , and the opportunity to achieve a sense of completion are important to most , other factors important to quality at the end of life differ by role and by individual . Efforts to evaluate and improve patients ' and families ' experiences at the end of life must account for diverse perceptions of quality . JAMA . 2000;284:2476 - 2482 Objectives For the measurement of patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 % , precision 4.4 % ) . The precise search filter had a sensitivity of 93.1 % and a precision of 9.4 % . Both filters performed very well in the validation sets . Conclusion The use of these search filters will contribute to evidence -based selection of measurement instruments in all medical fields Patients with advanced cancer frequently express positive attitudes and can be unduly optimistic about the potential benefits of treatment . In order to evaluate an illusory domain in the context of advanced cancer , we developed a scale of will to live and characterized the beliefs that patients held about the curability of their cancer , and how committed they were to using alternative treatments . A measure of quality of life was used as the dependent variable in order to assess the association between these attributes . After a preliminary exploration confirmed the presence of an illusory domain , these concepts were prospect ively tested in 149 ambulant patients with advanced cancer who attended for palliative systemic treatment , radiation treatment or supportive care . The scale of global quality of life was reliable ( Cronbach 's alpha coefficient 0.72 ) . The distribution of the scores of will to live was skewed , with no respondent scoring poorly , and the scale was reliable ( Cronbach 's alpha coefficient 0.82 ) . The scale of belief in curability showed diverse beliefs . In some cases , there was a discrepancy between respondents ' beliefs in curability and what they believed to be the report by their doctors . There was also an association between a committed use of alternative treatments and a belief in the curability of the cancer ( p<0.001 ) . In a multiple regression analysis , both will to live and performance status remained associated with better quality of life scores after adjustment for other relevant variables ( p<0.05 and < 0.001 , respectively ) . These results suggest that positive illusory beliefs can be measured and are an important component of adaption for some patients with advanced cancer . Furthermore , this illusory domain may influence the perception and measurement of quality of life The aim of this study was to evaluate the feasibility , reliability and compliance of a new instrument , a diary to monitor physical symptoms for patients with cancer in the palliative phase of their illness . The development of the diary took place in three phases : two pilot studies and one intervention study . In Pilot I , reliability was tested within 13 pairs of patients and their proxy in a patient-proxy comparison . Pilot II was performed to test the feasibility of the instrument among 47 frail elderly . In the intervention study among patients with cancer in the palliative phase , the feasibility as well as the compliance has been tested . The phases have been completed with good results : reliability ( ICC ) of prevalent symptoms was above 0.75 , good feasibility and good compliance . The Symptom Monitor can be used by patients and doctors as an instrument to monitor physical symptoms . The effectiveness of the use of this diary for improvement in treatment of symptoms in the palliative phase of cancer is being tested in a r and omized clinical trial The Functional Assessment of Chronic Illness Therapy ( FACIT ) system provides a general , multidimensional measure of health-related quality of life ( FACT-G ) that can be augmented with disease or symptom-specific subscales . The 19-item palliative care subscale of the FACIT system has undergone little psychometric evaluation to date . The aim of this paper is to report the internal consistency , factor structure , and construct validity of the instrument using the palliative care subscale ( FACIT-Pal ) . Two hundred fifty-six persons with advanced cancer in a r and omized trial testing a palliative care psychoeducational intervention completed the 46-item FACIT-Pal at baseline . Internal consistency was greater than 0.74 for all subscales and the total score . Seventeen of the 19 palliative care subscale items loaded onto the four-factor solution of the established core measure ( FACT-G ) . As hypothesized , total scores were correlated with measures of symptom intensity ( r=-0.73 , P<0.001 ) and depression ( r=-0.75 , P<0.001 ) . The FACIT-Pal was able to discriminate between participants who died within three months of completing the baseline and participants who lived for at least one year after completing the baseline assessment ( t=-4.05 , P<0.001 ) . The functional well-being subscale discriminated between participants who had a Karnofsky performance score of 70 and below and participants with a Karnofsky performance score of 80 and above ( t=3.40 , P<0.001 ) . The findings support the internal consistency reliability and validity of the FACIT-Pal as a measure of health-related quality of life for persons with advanced cancer OBJECTIVE To determine the impact on a responder type analysis of using three published methods to obtain the minimally important difference ( MID ) on the conclusion of a r and omized controlled trial ( RCT ) . STUDY DESIGN AND SETTING Using data from an RCT of supportive-expressive group therapy ( SEGT-intervention ) vs. st and ard care ( control ) in women with metastatic breast cancer , we measured individual responsiveness to change according to three levels of predefined MID ( 0.2 SD , 0.5 SD , and 1 st and ard error of measurement ) of the following six vali date d question naires : Profile of Mood States , Impact of Event Scale , Psychosocial Adjustment to Illness Scale , EORTC Quality -of-Life Question naire Core-30 , Mental Adjustment to Cancer , and a pain visual analog scale . The proportion of women improved by SEGT and the number needed to treat according to three levels of MID were calculated . RESULTS There was no consistent difference in the net proportion of women improving with the SEGT vs. control arm according to the three different levels of MID . CONCLUSION The choice between different levels of distribution-based MID did not make an important difference in the net proportion of women improving with the SEGT . Future research should compare MID derived from clinical anchors , in particular patient opinions The purpose of the study was to investigate psychometric properties of CAMPAS-R , an instrument for prospect ively monitoring patients ' symptoms and needs during palliative care at home . CAMPAS-R was piloted for face and content validity and then administered alongside criterion measures to a home care sample . Cronbach 's alpha was used to test internal consistency and criterion-related validity was tested by non-parametric correlation with Brief Pain Inventory ( BPI ) , Hospital Anxiety and Depression Scale ( HADS ) and EORTC QLQ-C30 . Predictive validity was assessed by relating CAMPAS-R scores to survival . One hundred and nine patients were recruited to the study . Good reliability and high correlations between CAMPAS-R and criterion measures were found . Predictive validity was demonstrated by significant differences in symptom scores between groups differing in length of survival . CAMPAS-R is acceptable to patients , families and primary care professionals and is a valid , reliable instrument , which has the benefit of being easy to score A cross-validation of the Karnofsky Performance Status ( KPS ) and quality of life ( QOL ) as measured by item 30 of the quality of life question naire developed by the European Organization for Research and Treatment of Cancer Study Group ( EORTC QLQ-C30 ) was conducted using ordered logit analysis and prospect i ve data from a continuous sample of 139 lung cancer patients . The QOL is found to be a much broader concept than the KPS , since it likely captures not only physical functioning but also functioning in the non-physical dimensions of social , emotional , and possibly cognitive well-being as well as the level of distress in the physical dimensions of pain , breathing and fatigue . These results suggest that the palliative treatment of advanced cancer and the terminally ill should be guided by a broad concept of well-being that goes beyond one based only on physical functioning The purpose of this study was to establish whether or not readiness for death , as an indicator of healthy dying , is a measurable concept . Review of relevant literature revealed consensus regarding the universality of a human need for healthy dying . A theory of healthy dying was derived from the Rogerian paradigm . The McCanse Readiness for Death Instrument ( MRDI ) was constructed , which included indicators of physiological , psychological , sociological , and spiritual aspects of " healthy " field pattern as death is developmentally approached . The MRDI was a 26-item structured interview question naire which generated interval-ratio data through a visual analog scale . A pretest was conducted with a sample of 9 volunteer patients drawn from a small suburban outpatient hospice . The MRDI was concurrently administered to dying individuals , their primary caregivers , and their primary hospice nurses . Correlations between dying individuals ' scores and their primary caregivers ' estimates of patient death readiness as well as between patients and their primary hospice nurses were very encouraging . Cronbach 's coefficient alpha for internal consistency reliability was .59 . Content validity was supported by consensus of an expert panel of practicing hospice nurses . Construct validity was demonstrated through legitimate placement of the concept , healthy death readiness , within the theoretical web which supported it . The MRDI was then administered to a sample of 31 terminally-ill individuals , their primary caregivers , and their primary hospice nurses drawn from larger , urban hospice population s in three geographic areas of the United States . The MRDI was also administered to a contrast group of 39 cardiac-impaired individuals who were not terminally-ill . Overall internal consistency of the MRDI was found to be quite favorable ( alpha = .76 ) . Debilitating illness and actual mortality in the study sample precluded and /or confounded estimates of test-retest reliability . Convergent validity of the MRDI was indicated by significant correlations between patients ' scores and primary caregivers ' estimates ( r = .35 , p < .05 ) and between patients ' scores and primary hospice nurses ' estimates ( r = .53 , p < .01 ) . Discriminant validity of the MRDI was demonstrated by a significant mean difference between the group of terminally-ill patients and the group of non-terminal , cardiac-impaired patients ( t = 1.76 , p < .01 ) This study describes a new clinical tool for needs assessment in palliative care : the Problems and Needs in Palliative Care question naire ( PNPC ) . It was developed to support the provision of care tailored to the specific dem and s of patients , which only can be provided when their needs are clearly identified . To test validity and reliability , 64 patients with metastatic cancer living at home completed the PNPC . Of 140 initial items , 2 were deleted because of low response . No important topics were missing . Dimensions were proposed to organize the problems and needs in a logical and practical array for use in individual patients , and to enable statistical analysis of patient-groups . Reliability analysis supported the proposed dimensions , with Cronbach 's alpha coefficient > 0.70 for dimensions with > or = 5 items , and alpha > 0.65 for the 3- and 4-item dimensions . However , the dimensions ' physical symptoms ' and ' social issues ' lacked coherency with some low item-total correlations . The PNPC demonstrated convergent validity with the European Organization for Research and Treatment of Cancer ( EORTC ) and COOP-WONCA quality -of-life measures . These data are a first step in validating the PNPC , although the ' social issues ' dimension needs reconsideration . Further studies are needed to evaluate clinical use |
13,502 | 25,323,413 | For secondary prevention , the results showed that the ICD is considered cost-effective in patients with more risk .
For primary prevention , the cost-effectiveness of ICD has been widely studied , but uncertainty about its cost-effectiveness remains .
The cost-effectiveness ratios vary between studies depending on the patient characteristics , methodology , perspective , and national setting s. Among the European studies , the conclusions are varied , where the ICD is considered cost-effective or not dependent on the study | The aim of this paper was to review the cost-effectiveness studies of implantable cardioverter defibrillators ( ICD ) for primary or secondary prevention of sudden cardiac death ( SCD ) . | More than 1 million Americans per year have acute myocardial infa rct ion ( 1 ) . Those who survive to hospital discharge have a 5 % to 10 % risk for dying suddenly within the first year ( 27 ) . Prevention of those sudden deaths is an important goal , and several approaches have been used to accomplish it . Secondary prevention with type I antiarrhythmic drugs has been unsuccessful ( 8) . Prophylactic use of amiodarone has significantly reduced death after myocardial infa rct ion in some but not all r and omized trials . Quantitative overviews of these studies suggest that amiodarone reduces mortality rates by 10 % to 20 % ( 9 , 10 ) . Recent studies of the implantable cardioverter defibrillator ( ICD ) in patients who have no history of sustained arrhythmia have also had mixed results , with positive results in patients with unsustained ventricular tachycardia ( 11 , 12 ) and negative results in patients with reduced ejection fraction and positive results on signal-averaged electrocardiography ( 13 ) . The use of prophylactic ICD has nevertheless attracted great interest because of the demonstrated efficacy of the device in patients who have had a documented episode of ventricular fibrillation or sustained ventricular tachycardia ( 1416 ) . Although ongoing or planned r and omized , controlled trials ( 17 , 18 ) will clarify the role of ICDs and amiodarone therapy in patients who have had myocardial infa rct ions , the results of these trials will not be available until late 2001 at the earliest . We previously showed that ICDs can be cost-effective in patients who have survived an episode of ventricular fibrillation or sustained ventricular tachycardia ( 19 ) . These findings can not be extrapolated to prophylactic use of ICDs in patients who have had myocardial infa rct ions because the risk for sudden death in such patients is lower . Indeed , the current st and ard of care for patients who have had myocardial infa rct ion does not include prophylactic antiarrhythmic therapy . With recent evidence of the efficacy of antiarrhythmia management in patients who have had myocardial infa rct ions , the potential cost-effectiveness of prophylactic antiarrhythmic therapy should be reassessed . In this study , we estimated survival and costs for patients with past myocardial infa rct ion who were treated with amiodarone , ICD , or no specific antiarrhythmic therapy . We evaluated the level of efficacy needed to make prophylactic therapy with an ICD or amiodarone cost-effective in three groups of patients with past myocardial infa rct ion who were stratified by left ventricular ejection fraction . Methods We used a decision model to estimate the length of life and expenditures for patients who had myocardial infa rct ion without symptomatic , sustained ventricular arrhythmia and who received one of three treatment strategies : ICD , amiodarone therapy , or no antiarrhythmic therapy ( Figure 1 ) . We stratified patients into three groups according to ejection fraction : less than or equal to 0.3 , 0.31 to 0.4 , and greater than 0.4 . Although the ability of many clinical factors to predict the risk for sudden cardiac death has been analyzed and several independent risk factors have been identified ( 20 ) , ejection fraction has consistently been the single most powerful predictor of sudden cardiac death ( 2124 ) . Figure 1 . The decision model . The square node on the left represents a choice among three alternative treatments : implantable cardiac defibrillator ( ICD ) , amiodarone , and no antiarrhythmic treatment . Circles represent chance nodes . Patients who receive an ICD are at risk for death from the implant procedure . Patients who do not die of ICD implantation and patients who are receiving amiodarone or no treatment enter the Markov tree ( denoted by rectangles containing circles and an arrow ) . The Markov tree represents the clinical events that can occur during each 1-month period as a patient is followed until death . During each 1-month period , a patient may die from arrhythmic or nonarrhythmic cardiac causes and may also die of noncardiac causes . If none of these events occur , the patient remains well for the 1-month period . Patients who have an ICD may have a lead infection or failure that causes them to withdraw from treatment ( and to switch to no antiarrhythmic therapy ) . Patients who receive amiodarone are at risk for amiodarone toxicity . In our analysis , a patient may die of toxicity , withdraw from treatment ( and switch to no antiarrhythmic therapy ) , or have acute toxicity that does not require discontinuation . We adhered to the recommendations of the Panel on Cost-effectiveness in Health and Medicine ( 25 , 26 ) . We used a societal perspective to evaluate health benefits and costs , discounting each at a rate of 3 % per year . We performed one-way sensitivity analyses on all of the model variables , as well as selected two-way , three-way , and n-way ( Monte Carlo ) probabilistic sensitivity analyses ( 27 ) . Decision Model We developed a Markov model ( 28 , 29 ) ( SMLTree decision analysis software , version 2.9 , J. Hollenberg , New York , New York ) by modifying a model used previously to assess the cost-effectiveness of ICDs or amiodarone in patients who had experienced sustained ventricular arrhythmia ( 19 , 30 ) ( Figure 1 ) . Our current model includes the possibility of no antiarrhythmic therapy and uses data relevant to the lower-risk population of patients who have survived myocardial infa rct ion . The model tracks a cohort of patients who received prophylactic ICD ( implanted without a thoracotomy ) , amiodarone therapy , or no antiarrhythmic therapy . Patients who received an ICD were at risk for procedural death . Patients who survived ICD implantation , patients treated with amiodarone , and patients who received no antiarrhythmic therapy entered a Markov tree ( Figure 1 ) . Each month , these patients were at risk for sudden cardiac death , nonsudden cardiac death , and noncardiac death . We assumed that 2 % of the ICD-treated patients would have the ICD removed because of infection or lead complications during the first year and that 1 % of surviving patients would withdraw from ICD therapy in each subsequent year ( 3133 ) . Similarly , we assumed that 10 % of the amiodarone-treated patients would withdraw from therapy because of toxicity during the first year and that 5 % of surviving patients would withdraw in each subsequent year ( 3445 ) . Because the use of antiarrhythmic therapy in the postmyocardial infa rct ion population would be prophylactic , we assumed that crossovers between the ICD and amiodarone strategies would be less likely . Therefore , patients who withdrew from one antiarrhythmic treatment would be withdrawn from prophylactic treatment . Patient Sample Our base-case analyses evaluated the cost-effectiveness of each antiarrhythmic management strategy in three cohorts of patients defined by ejection fraction ( Table 1 ) . We obtained mortality and inpatient cost data for patients from the Myocardial Infa rct ion Triage and Intervention ( MITI ) patient registry ( 46 ) who had had myocardial infa rct ion . Between 1988 and 1994 , approximately 40 000 patients were admitted to cardiac care units in 19 hospitals in Seattle , Washington . Hospitals participating in the registry include 2 university hospitals , 2 staff-model health maintenance organization hospitals , 1 Veterans Affairs hospital , and 14 community hospitals . During most of the study period , 10 of the participating hospitals had on-site catheterization laboratories and 5 performed bypass surgery . During the study period , 12 000 patients presented with an acute myocardial infa rct ion ; of these , ejection fraction was measured in approximately 3000 . Table 1 . Clinical Characteristics of the Myocardial Infa rct ion Triage and Intervention Patient Sample Patients with ejection fractions of 0.3 or less had a mean age ( SD ) of 66.5 11.92 years ( range , 26 to 95 years ) , 24.6 % 43.1 % had a history of congestive heart failure , 62.8 % 48.4 % received an initial catheterization , and 26.6 % 44.3 % underwent initial revascularization . Patients with ejection fractions between 0.31 and 0.4 had a mean age of 63.5 12.22 years ( range , 36 to 97 years ) , 11.0 % 31.3 % had a history of congestive heart failure , 73.2 % 44.3 % underwent catheterization , and 37.6 % 48.4 % had revascularization . Finally , patients with ejection fractions greater than 0.4 had a mean age of 61.5 11.83 years ( range , 26 to 92 years ) , 3.5 % 18.4 % had a history of congestive heart failure , 88.0 % 32.4 % received an initial catheterization , and 48.0 % 50 % underwent revascularization . We compared the characteristics of patients who had ejection fraction measurements with those of patients in the MITI registry for whom ejection fraction was not measured . The clinical characteristics listed in Table 1 differed significantly between these groups , but the rates of sudden cardiac , nonsudden cardiac , noncardiac , and overall mortality did not differ significantly after we controlled for age , sex , and cardiac history ( 24 ) . From the MITI registry , we obtained monthly probabilities of cardiac death for the three ejection fraction cohorts . The MITI project used hospital discharge summaries and death certificates to identify patients who died of cardiac causes during follow-up while in or out of the hospital ( 47 ) . We classified cardiac deaths that occurred in neither a hospital nor a nursing home as sudden and potentially preventable by arrhythmic therapy ; we classified as nonsudden the cardiac deaths that occurred in a hospital or a nursing home . We recognized the limitations of this classification system and therefore analyzed a range of ICD efficacies . Table 1 summarizes the probabilities of sudden and nonsudden cardiac death for the three cohorts over time . To estimate life expectancy after the end of follow-up in the MITI cohort , we extrapolated the annual cardiac mortality rate for subsequent years from that observed during follow-up and assumed that the noncardiac mortality rate would equal that in the general U.S. population ( 48 ) . Effectiveness of Background —The implantable cardioverter-defibrillator ( ICD ) is an effective but expensive device . We used prospect ively collected data from a large r and omized clinical trial of secondary prevention of life-threatening ventricular arrhythmias to determine the cost-effectiveness of the ICD compared with antiarrhythmic drug ( AAD ) therapy , largely with amiodarone . Methods and Results —Charges for initial and repeat hospitalizations , emergency room , and day surgery stays and the costs of antiarrhythmic drugs were collected on 1008 patients . Detailed records of all other medical encounters and expenses were collected on a subgroup of 237 patients . Regression models were then created to attribute these expenses to the rest of the patients . Charges were converted to 1997 costs using st and ard methods . Costs and life years were discounted at 3 % per year . Three-year survival data from the Antiarrhythmics Versus Implantable Defibrillators trail were used to calculate the base-case cost-effectiveness ( C/E ) ratio . Six-year , twenty-year , and lifetime C/E ratios were also estimated . At 3 years , total costs were $ 71 421 for a patient taking AADs and $ 85 522 for a patient using an ICD , and the ICD provided a 0.21-year survival benefit over AAD treatment . The base-case C/E ratio was thus $ 66 677 per year of life saved by the ICD compared with AAD therapy ( 95 % CI , $ 30 761 to $ 154 768 ) . Six- and 20-year C/E ratios remained stable between $ 68 000 and $ 80 000 per year of life saved . Conclusions —The ICD is moderately cost-effective for secondary prevention of life-threatening ventricular arrhythmias , as judged from prospect ively collected data in a r and omized clinical trial Background —In the Canadian Implantable Defibrillator Study ( CIDS ) , we assessed the cost-effectiveness of the implantable cardioverter-defibrillator ( ICD ) in reducing the risk of death in survivors of previous ventricular tachycardia ( VT ) or fibrillation ( VF ) . Methods and Results —Healthcare re source use was collected prospect ively on the first 430 patients enrolled in CIDS ( n=212 ICD , n=218 amiodarone ) . Mean cost per patient , adjusted for censoring , was computed for each group based on initial therapy assignment . Incremental cost-effectiveness of ICD therapy was computed as the ratio of the difference in cost ( ICD minus amiodarone ) to the difference in life expectancy ( both discounted at 3 % per year ) . All costs are in 1999 Canadian dollars ( C$ 1 ≈ US$ 0.65 ) . Over 6.3 years , mean cost per patient in the ICD group was C$ 87 715 versus C$ 38 600 in the amiodarone group ( difference C$ 49 115 ; 95 % CI C$ 25 502 to C$ 69 508 ) . Life expectancy for the ICD group was 4.58 years versus 4.35 years for amiodarone ( difference 0.23 , 95 % CI −0.09 to 0.55 ) , for incremental cost-effectiveness of ICD therapy of C$ 213 543 per life-year gained . ICD benefit was greater in patients with low left ventricular ejection fraction ( < 35 % ) , and cost-effectiveness in this group was more attractive ( C$ 108 484 ) . Alternative extrapolations of survival benefit and costs to 12 years indicated cost-effectiveness in the range of C$ 100 000 to C$ 150 000 per life-year gained . Conclusions —At C$ 213 543 , the value for the money offered by ICD therapy is not attractive by currently accepted st and ards . Further research is warranted to identify the indications and patient subgroups for whom ICDs are a cost-effective use of re sources BACKGROUND Many r and omized clinical trials have demonstrated the effectiveness of the implantable cardioverter-defibrillator ( ICDs ) in death reduction of chronic heart failure ( CHF ) patients . Some developed countries studies have evaluated its cost-effectiveness , but these data are not applicable to Brazil . OBJECTIVE To evaluate the cost-effectiveness of ICD in CHF patients under two perspectives in Brazil : public and supplementary health systems . METHODS A Markov model was developed to analyze the incremental cost-effectiveness ratio ( ICER ) of ICD compared to conventional therapy in patients with CHF . Effectiveness was measured in quality -adjusted life years ( QALYs ) . We search ed the literature for data regarding effectiveness and complications . Costs were retrieved from public and health insurances reimbursement codebooks and from mean cost of admissions from a public and a private hospital . One-way sensitivity analysis was performed in all variables of the model . RESULTS ICER was R$ 68,318/QALY in the public and R$ 90,942/QALY in the private perspective . These values are much higher than the one suggested by the World Health Organization of 3 times the gross domestic product per head ( R$ 40,545 in Brazil ) . The results were sensitive to the cost of the device , battery replacement interval and ICD effectiveness . In a simulation resembling MADIT-I population survival and ICD benefit , ICER was R$ R$ 23,739/QALY in the public and R$ 33,592/QALY in the private perspective . CONCLUSION The ICER of ICD is elevated in the general ICC population , in either the public or private perspective . A more favorable result occurs in patients with a high sudden death risk BACKGROUND Patients surviving ventricular fibrillation ( VF ) or sustained ventricular tachycardia ( VT ) are at a high risk of death due to a recurrence of arrhythmia . The implantable cardioverter defibrillator ( ICD ) terminates VT or VF , but it is not known whether this device prolongs life in these patients compared with medical therapy with amiodarone . METHODS AND RESULTS A total of 659 patients with resuscitated VF or VT or with unmonitored syncope were r and omly assigned to treatment with the ICD or with amiodarone . The primary outcome measure was all-cause mortality , and the secondary outcome was arrhythmic death . A total of 328 patients were r and omized to receive an ICD . A thoracotomy was done in 33 , no ICD was implanted in 18 , and the rest had a nonthoracotomy ICD . All 331 patients r and omized to amiodarone received it initially . At 5 years , 85.4 % of patients assigned to amiodarone were still receiving it at a mean dose of 255 mg/day , 28.1 % of ICD patients were also receiving amiodarone , and 21.4 % of amiodarone patients had received an ICD . A nonsignificant reduction in the risk of death was observed with the ICD , from 10.2 % per year to 8.3 % per year ( 19.7 % relative risk reduction ; 95 % confidence interval , -7.7 % to 40 % ; P=0.142 ) . A nonsignificant reduction in the risk of arrhythmic death was observed , from 4.5 % per year to 3.0 % per year ( 32.8 % relative risk reduction ; 95 % confidence interval , -7.2 % to 57.8 % ; P=0.094 ) . CONCLUSIONS A 20 % relative risk reduction occurred in all-cause mortality and a 33 % reduction occurred in arrhythmic mortality with ICD therapy compared with amiodarone ; this reduction did not reach statistical significance BACKGROUND The recently reported Multicenter Automatic Defibrillator Implantation Trial ( MADIT ) showed improved survival in selected asymptomatic patients with coronary disease and nonsustained ventricular tachycardia . The economic consequences of defibrillator management in this patient population are unknown . METHODS AND RESULTS Patients were followed up to quantify their use of healthcare services , including hospitalizations , physician visits , medications , laboratory tests , and procedures , during the trial . The costs of these services , including the costs of the defibrillator , were determined in patients r and omized to defibrillator and nondefibrillator therapy . Incremental cost-effectiveness ratios were calculated by relating these costs to the increased survival associated with the use of the defibrillator . The average survival for the defibrillator group over a 4-year period was 3.66 years compared with 2.80 years for conventionally treated patients . Accumulated net costs were $ 97,560 for the defibrillator group compared with $ 75,980 for individuals treated with medications alone . The result ing incremental cost-effectiveness ratio of $ 27,000 per life-year saved compares favorably with other cardiac interventions . Sensitivity analyses showed that the incremental cost-effectiveness ratio would be reduced to approximately $ 23,000 per life-year saved if transvenous defibrillators were used instead of the older devices , which required thoracic surgery for implantation . CONCLUSIONS An implanted cardiac defibrillator is cost-effective in selected individuals at high risk for ventricular arrhythmias Background —Three r and omized clinical trials showed that implantable cardioverter-defibrillators ( ICDs ) reduce the risk of death in survivors of ventricular tachyarrhythmias , but the cost per year of life gained is high . A sub study of the Canadian Implantable Defibrillator Study ( CIDS ) showed that 3 clinical factors , age ≥70 years , left ventricular ejection fraction ≤35 % , and New York Heart Association class III , predicted the risk of death and benefit from the ICD . We estimated the extent to which selecting patients for ICD therapy based on these risk factors makes ICD therapy more economically attractive . Methods and Results — Patients in CIDS were grouped according to whether they had ≥2 of 3 risk factors . Incremental cost-effectiveness of ICD therapy was computed as the ratio of the difference in mean cost to the difference in life expectancy between the 2 groups . Over 6.3 years , the mean cost per patient in the ICD group was Canadian ( C ) $ 87 715 versus $ 38 600 in the amiodarone group ( C$ 1≈US$0.67 ) . Life expectancy for the ICD group was 4.58 years versus 4.35 years for amiodarone , for an incremental cost-effectiveness of ICD therapy of C$ 213 543 per life-year gained . The cost per life-year gained in patients with ≥2 factors was C$ 65 195 , compared with C$ 916 659 with < 2 risk factors . Conclusions —The cost-effectiveness of ICD therapy varies by patient risk factor status . The use of ICD therapy in patients who have ≥2 risk factors of age ≥70 years , left ventricular ejection fraction ≤35 % , and NYHA class III is C$ 65 195 to gain a year of life BACKGROUND Eight r and omized trials have evaluated whether the prophylactic use of an implantable cardioverter-defibrillator ( ICD ) improves survival among patients who are at risk for sudden death due to left ventricular systolic dysfunction but who have not had a life-threatening ventricular arrhythmia . We assessed the cost-effectiveness of the ICD in the population s represented in these primary -prevention trials . METHODS We developed a Markov model of the cost , quality of life , survival , and incremental cost-effectiveness of the prophylactic implantation of an ICD , as compared with control therapy , among patients with survival and mortality rates similar to those in each of the clinical trials . We modeled the efficacy of the ICD as a reduction in the relative risk of death on the basis of the hazard ratios reported in the individual clinical trials . RESULTS Use of the ICD increased lifetime costs in every trial . Two trials -- the Coronary Artery Bypass Graft ( CABG ) Patch Trial and the Defibrillator in Acute Myocardial Infa rct ion Trial (DINAMIT)--found that the prophylactic implantation of an ICD did not reduce the risk of death and thus was both more expensive and less effective than control therapy . For the other six trials -- the Multicenter Automatic Defibrillator Implantation Trial ( MADIT ) I , MADIT II , the Multicenter Unsustained Tachycardia Trial ( MUSTT ) , the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation ( DEFINITE ) trial , the Comparison of Medical Therapy , Pacing , and Defibrillation in Heart Failure ( COMPANION ) trial , and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)--the use of an ICD was projected to add between 1.01 and 2.99 quality -adjusted life-years ( QALY ) and between 68,300 dollars and 101,500 dollars in cost . Using base-case assumptions , we found that the cost-effectiveness of the ICD as compared with control therapy in these six population s ranged from 34,000 dollars to 70,200 dollars per QALY gained . Sensitivity analyses showed that this cost-effectiveness ratio would remain below 100,000 dollars per QALY as long as the ICD reduced mortality for seven or more years . CONCLUSIONS Prophylactic implantation of an ICD has a cost-effectiveness ratio below 100,000 dollars per QALY gained in population s in which a significant device-related reduction in mortality has been demonstrated BACKGROUND Patients with reduced left ventricular function after myocardial infa rct ion are at risk for life-threatening ventricular arrhythmias . This r and omized trial was design ed to evaluate the effect of an implantable defibrillator on survival in such patients . METHODS Over the course of four years , we enrolled 1232 patients with a prior myocardial infa rct ion and a left ventricular ejection fraction of 0.30 or less . Patients were r and omly assigned in a 3:2 ratio to receive an implantable defibrillator ( 742 patients ) or conventional medical therapy ( 490 patients ) . Invasive electrophysiological testing for risk stratification was not required . Death from any cause was the end point . RESULTS The clinical characteristics at base line and the prevalence of medication use at the time of the last follow-up visit were similar in the two treatment groups . During an average follow-up of 20 months , the mortality rates were 19.8 percent in the conventional-therapy group and 14.2 percent in the defibrillator group . The hazard ratio for the risk of death from any cause in the defibrillator group as compared with the conventional-therapy group was 0.69 ( 95 percent confidence interval , 0.51 to 0.93 ; P=0.016 ) . The effect of defibrillator therapy on survival was similar in subgroup analyses stratified according to age , sex , ejection fraction , New York Heart Association class , and the QRS interval . CONCLUSIONS In patients with a prior myocardial infa rct ion and advanced left ventricular dysfunction , prophylactic implantation of a defibrillator improves survival and should be considered as a recommended therapy BACKGROUND One of the major drawbacks of implantable cardioverter-defibrillator ( ICD ) treatment is the limited device service life . Thus far , data concerning ICD longevity under clinical circumstances are scarce . In this study , the ICD service life was assessed in a large cohort of ICD recipients . OBJECTIVE To assess the battery longevity of ICDs under clinical circumstances . METHODS All patients receiving an ICD in the Leiden University Medical Center were included in the analysis . During prospect ively recorded follow-up visits , reasons for ICD replacement were assessed and categorized as battery depletion and non-battery depletion . Device longevity and battery longevity were calculated . The impact of device type , generation , manufacturer , the percentage of pacing , the pacing output , and the number of shocks on the battery longevity was assessed . RESULTS Since 1996 , 4673 ICDs were implanted , of which 1479 ICDs ( 33 % ) were replaced . Mean device longevity was 5.0 ± 0.1 years . A total of 1072 ( 72 % ) ICDs were replaced because of battery depletion . Mean battery longevity of an ICD was 5.5 ± 0.1 years . When divided into different types , mean battery longevity was 5.5 ± 0.2 years for single-chamber ICDs , 5.8 ± 0.1 for dual-chamber ICDs , and 4.7 ± 0.1 years for cardiac resynchronization therapy-defibrillators ( P < .001 ) . Devices implanted after 2002 had a significantly better battery longevity as compared with devices implanted before 2002 ( 5.6 ± 0.1 years vs 4.9 ± 0.2 years ; P < .001 ) . In addition , large differences in battery longevity between manufacturers were noted ( overall log-rank test , P < .001 ) . CONCLUSIONS The majority of ICDs were replaced because of battery depletion . Large differences in longevity exist between different ICD types and manufacturers . Modern ICD generations demonstrated improved longevity BACKGROUND Patients who survive life-threatening ventricular arrhythmias are at risk for recurrent arrhythmias . They can be treated with either an implantable cardioverter-defibrillator or antiarrhythmic drugs , but the relative efficacy of these two treatment strategies is unknown . METHODS To address this issue , we conducted a r and omized comparison of these two treatment strategies in patients who had been resuscitated from near-fatal ventricular fibrillation or who had undergone cardioversion from sustained ventricular tachycardia . Patients with ventricular tachycardia also had either syncope or other serious cardiac symptoms , along with a left ventricular ejection fraction of 0.40 or less . One group of patients was treated with implantation of a cardioverter-defibrillator ; the other received class III antiarrhythmic drugs , primarily amiodarone at empirically determined doses . Fifty-six clinical centers screened all patients who presented with ventricular tachycardia or ventricular fibrillation during a period of nearly four years . Of 1016 patients ( 45 percent of whom had ventricular fibrillation , and 55 percent ventricular tachycardia ) , 507 were r and omly assigned to treatment with implantable cardioverter-defibrillators and 509 to antiarrhythmic-drug therapy . The primary end point was overall mortality . RESULTS Follow-up was complete for 1013 patients ( 99.7 percent ) . Overall survival was greater with the implantable defibrillator , with unadjusted estimates of 89.3 percent , as compared with 82.3 percent in the antiarrhythmic-drug group at one year , 81.6 percent versus 74.7 percent at two years , and 75.4 percent versus 64.1 percent at three years ( P<0.02 ) . The corresponding reductions in mortality ( with 95 percent confidence limits ) with the implantable defibrillator were 39+/-20 percent , 27+/-21 percent , and 31+/-21 percent CONCLUSIONS Among survivors of ventricular fibrillation or sustained ventricular tachycardia causing severe symptoms , the implantable cardioverter-defibrillator is superior to antiarrhythmic drugs for increasing overall survival Sudden cardiac death struck approximately 360 000 persons in the United States in 1990 [ 1 , 2 ] . Defined as death that occurs within 1 hour of the onset of symptoms , sudden cardiac death accounts for about one half of all deaths from heart disease [ 2 ] . Sudden cardiac death occurs primarily in patients who have an established history of heart disease , particularly those with a history of severe congestive heart failure , myocardial infa rct ion , or sustained ventricular arrhythmia [ 3 ] . The therapeutic alternatives are treatment with antiarrhythmic drugs or treatment with an implantable cardioverter defibrillator ( ICD ) [ 4 ] . Type Ia antiarrhythmic agents ( for example , procainamide ) were previously a mainstay of pharmacologic therapy , but recent evidence has raised concern about their effectiveness and potential toxicity [ 5 - 8 ] . In 1991 , it was found that the type Ic agents encainide and flecainide increased mortality when used to suppress ventricular ectopy after myocardial infa rct ion . This unexpected finding further limited the choice of antiarrhythmic drugs [ 9 ] . Amiodarone is one of the most promising pharmacologic alternatives [ 10 - 14 ] . However , amiodarone therapy is complicated by lengthy loading regimens ; persistence of the drug in adipose tissue for long periods ; and severe adverse effects , including pulmonary fibrosis and thyroid abnormalities [ 15 , 16 ] . With the development of ICDs that can be implanted without thoracotomy ( and possibly during an outpatient procedure ) , use of an ICD is now a practical therapeutic alternative to antiarrhythmic drug therapy [ 4 ] . Although ICDs are remarkably effective in terminating ventricular arrhythmias [ 17 - 20 ] , they are expensive ( $ 40 000 to $ 60 000 for implantation ) , and the extent to which they extend life is unknown [ 21 ] . Ongoing or planned r and omized , controlled trials [ 19 , 20 , 22 - 27 ] will clarify the role of ICDs and drug therapy for the prevention of sudden cardiac death , but their results will not be available for several years . Economic analyses have suggested that ICDs have favorable cost-effectiveness ratios [ 28 - 32 ] , but these analyses were based on controversial assumptions about efficacy in improving survival [ 28 , 30 , 31 ] ; compared the implantation of an ICD with an expensive alternative , such as electrophysiologically guided therapy [ 29 , 31 , 32 ] ; or limited the use of ICDs to extremely high-risk patients [ 28 - 32 ] . In this study , we used data from ongoing r and omized trials and data on the costs of third-generation ICDs to evaluate the cost-effectiveness of treatment with an ICD ( implanted without thoracotomy ) relative to empirical therapy with amiodarone . We determined the reduction in total mortality that ICD use would have to confer to reach specified cost-effectiveness ratios . Because the indications for ICD use may exp and the use of this therapy into new patient population s , we evaluated how the cost-effectiveness of treatment with an ICD varies when the device is used in a population that has a lower risk for sudden cardiac death than do survivors of cardiac arrest . Methods We used a decision model to estimate the quality -adjusted length of life and expenditures for a population of patients who received amiodarone or an ICD . We used the perspective of society and incorporated benefits and costs accordingly . We examined three treatment strategies ( Figure 1 ) . Patients who received the ICD-only regimen began treatment with an ICD and continued to receive this therapy regardless of subsequent arrhythmic events . Patients who received amiodarone only began treatment with amiodarone and continued to receive this drug as sole therapy regardless of subsequent arrhythmic events . They crossed over to receive an ICD only if they had intolerable side effects as a result of amiodarone use . Patients who received the amiodarone-to-ICD therapy began treatment with amiodarone and crossed over to ICD if they were subsequently resuscitated from ventricular fibrillation ( all survivors ) or from ventricular tachycardia ( 50 % of survivors ) or if severe drug toxicity occurred . We did not evaluate treatment strategies that used ICD and amiodarone simultaneously because evidence was not sufficient to assess the efficacy of this combined therapy . We discounted health benefits and costs using a 3 % annual discount rate , as recommended by a panel on cost-effectiveness analysis in health care [ 33 ] , and we did sensitivity analyses on all model variables . Figure 1 . Schematic representation of the decision model . Decision Model We developed a Markov model [ 34 , 35 ] ( Figure 1 , Appendix ) using SMLTree software ( version 2.9 , J. Hollenberg , New York , New York ) ; the model tracked a hypothetical cohort of patients over time . Each cohort began receiving one of the three therapeutic regimens : ICD only , amiodarone only , or amiodarone-to-ICD . Each month , a patient was at risk for ventricular fibrillation , ventricular tachycardia , nonarrhythmic cardiac death , noncardiac death , and illness or death from drug toxicity ( the latter was applicable only to patients who received amiodarone ) . Patients who had an ICD were also at risk for perioperative death . If a patient had ventricular fibrillation or ventricular tachycardia , the patient either died , survived with neurologic impairment , or survived without neurologic impairment ( Figure 2 ) . The model included a decrement in quality of life for patients who survived an arrhythmic event with neurologic sequelae [ 36 - 39 ] . Patients who were treated with amiodarone were at risk for acute drug toxicity ( Figure 2 ) . Figure 2 . Decision model subtrees . Top . Upper middle . Lower middle . Bottom . Quality of Life The Markov model incorporated adjustments for quality of life associated with current health , ICD or amiodarone therapy , arrhythmic events , ICD discharges ( shocks ) , and amiodarone toxicity . We used the time-tradeoff technique to calculate quality -adjusted life-years [ 40 , 41 ] . In the base-case analysis , we assumed that the quality of life of current health was 0.75 [ 39 ] , and we assumed that quality of life did not change as a result of ICD or amiodarone therapy . In sensitivity analyses , we evaluated the importance of changes in quality of life caused by ICD or amiodarone therapy . Effectiveness of Implantable Cardioverter Defibrillators We assumed that treatment with an ICD did not affect the frequency of arrhythmias but did increase the chance for surviving an arrhythmic event if one occurred . Evidence from r and omized trials and patient registries indicates that ICDs successfully treat life-threatening ventricular arrhythmias . In a registry that contained more than 600 patients with third-generation ICDs [ 17 ] , ventricular tachycardia was terminated successfully in 98.7 % of cases and ventricular fibrillation was converted in 98.9 % of cases . The Cardiac Arrest Survivors in Hamburg ( CASH ) study , a r and omized trial that compared ICD with pharmacologic therapy in survivors of cardiac arrest , reported a cardiac death rate of 0 % at 1 year among 59 patients treated with an ICD [ 16 , 19 , 20 , 42 ] . Other studies [ 18 , 43 - 46 ] have also reported low rates of sudden cardiac death in ICD recipients . In our base-case analysis , we assumed that ICDs successfully terminated arrhythmias at rates similar to those reported in the patient registry [ 17 ] ( Table 1 ) . Table 1 . Input Variables and Sources * The effect of ICD use on total mortality is less clear [ 67 - 70 ] . At approximately 1 year of follow-up , total mortality rates in the CASH study were 14.3 % in the group that received ICDs and 14.7 % in the group that received amiodarone ; the difference between the groups was not statistically significant [ 16 ] . However , this trial is incomplete and relatively small : Each treatment group contained fewer than 60 patients . In the Multicenter Automatic Defibrillator Implantation Trial ( MADIT ) , 196 patients who had a history of previous Q-wave infa rct ion , documented nonsustained ventricular tachycardia , an ejection fraction of 0.35 or less , and inducible sustained ventricular tachycardia ( shown on electrophysiologic testing ) that could not be suppressed by the infusion of procainamide were r and omly assigned to receive either an ICD or conventional pharmacologic care [ 25 ] . The trial was stopped early because 15 deaths occurred in the ICD group and 39 occurred in the usual care group , producing a hazard ratio for total mortality of 0.46 ( 95 % CI , 0.26 to 0.82 ) . This corresponds to Kaplan-Meier survival rates of 87 % in the ICD group and 65 % in the usual care group at approximately 2 years ( Moss AJ for the MADIT Investigators . Multicenter Automatic Implantable Defibrillator Trial [ MADIT ] . 17th Annual Scientific Session of the North American Society of Pacing and Electrophysiology . Seattle ; 1996 ) . The risk reduction found in MADIT may particularly favor ICD because selected patients were not suppressed by drug therapy and because the trial was discontinued early . Other large r and omized trials of ICD treatment are still ongoing and have not reported any results . Cost-effectiveness studies [ 28 , 30 , 31 ] ( with one exception [ 32 ] ) have assumed that patients who receive ICDs have substantial survival advantages . This assumption has been based on the results of nonr and omized trials , which are subject to selection bias because healthier patients may have had ICD implantation . Such bias precludes definitive inferences about the effect of ICDs on total mortality [ 21 , 71 ] . For our base-case analysis , therefore , we assumed that ICD use would reduce total mortality at 1 year by 20 % to 40 % relative to amiodarone therapy in patients who survive ICD implantation . This reduction was approximately constant over time . In sensitivity analyses , we examined reductions in total mortality by ICDs compared with amiodarone that varied from 5 % to 60 % . A reduction in total mortality of 30 % is a reasonable point estimate , given the current evidence . We assumed that the implantation of an ICD was associated with a perioperative mortality rate of 1 OBJECTIVES We sought to evaluate the cost implication s of the implantable cardioverter-defibrillator ( ICD ) , using utilization , cost , and survival data from the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II . BACKGROUND This trial showed that prophylactic implantation of a defibrillator reduces the rate of mortality in patients who experienced a previous myocardial infa rct ion and low left ventricular ejection fraction . Given the size of the eligible population , the cost effectiveness of the ICD has substantial implication s. METHODS Our research comprises the cost-effectiveness component of the r and omized controlled trial , MADIT-II , based on utilization , cost , and survival information from 1,095 U.S. patients who were assigned r and omly to receive an ICD or conventional medical care . Utilization data were converted to costs using a variety of national and hospital-specific data . The incremental cost-effectiveness ratio ( iCER ) was calculated as the difference in discounted costs divided by the difference in discounted life expectancy within 3.5 years . Secondary analyses included projections of survival ( using three alternative assumptions ) , corresponding cost assumptions , and the result ing cost-effectiveness ratios until 12 years after r and omization . RESULTS During the 3.5-year period of the study , the average survival gain for the defibrillator arm was 0.167 years ( 2 months ) , the additional costs were 39,200 dollars , and the iCER was 235,000 dollars per year-of-life saved . In three alternative projections to 12 years , this ratio ranged from 78,600 dollars to 114,000 dollars . CONCLUSIONS The estimated cost per life-year saved by the ICD in the MADIT-II study is relatively high at 3.5 years but is projected to be substantially lower over the course of longer time horizons Background : Implantable cardioverter defibrillators ( ICDs ) improve survival and extend lives of patients with severe heart disease . Objective : We sought to evaluate the impact of ICDs on health-related quality of life ( HRQOL ) during the first 3 years after implantation . Subjects : A total of 1089 patients from the Multicenter Automatic Defibrillator Implantation Trial II ( MADIT II ) were r and omized to an ICD or medical treatment only . Measures : Health Utility Index ( HUI3 ) at baseline , 3 , 12 , 24 , and 36 months following r and omization ; survival data . Research Design : We constructed mean profiles of HRQOL for living patients , estimated overall quality -adjusted life years ( QALYs ) , separately by treatment arm , and calculated cumulative QALY gains/losses as the difference between the areas under the treatment specific HRQOL profiles . Multivariate fixed effect regression models were developed to impute the missing HRQOL data using baseline patient characteristics ( age , gender , treatment , HUI3 score , diabetes , diuretics use , and NYHA class ) . Bootstrapped st and ard errors were calculated for the estimated differences in HRQOL gains/losses between treatment arms . Similarly , we performed subgroup analyses ( by gender , age , and baseline NYHA class , blood urine nitrogen , ejection fraction , and QRS ) . Results : There were no differences in QALYs loss for living patients by treatment group ( −0.037 , P = 0.64 ) or in overall QALYs loss by treatment group ( 0.043 , P = 0.37 ) over 3 years . In subgroup analysis , female subjects demonstrated a trend towards greater survival benefit ( 0.298 , P = 0.07 ) and overall QALYs ( 0.261 , P = 0.14 ) . Conclusions : Adverse effects of the ICD on HRQOL together with lower HRQOL among survivors may offset the 3-year survival benefits of ICDs BACKGROUND Rising costs of health care , partly as a result of costly therapeutic innovations , are of concern to both the medical profession and healthcare authorities . The implantable cardioverter-defibrillator ( ICD ) is still not remunerated by Dutch healthcare insurers . The aim of this study was to evaluate the cost-effectiveness of early implantation of the ICD in postinfa rct sudden death survivors . METHODS AND RESULTS Sixty consecutive postinfa rct survivors of cardiac arrest caused by ventricular tachycardia or fibrillation were r and omly assigned either ICD as first choice ( n = 29 ) or a tiered therapy starting with antiarrhythmic drugs and guided by electrophysiological ( EP ) testing ( n = 31 ) . Median follow-up was 729 days ( range , 3 to 1675 days ) . Fifteen patients died , 4 in the early ICD group and 11 in the EP-guided strategy group ( P = .07 ) . For quantitative assessment , the cost-effectiveness ratio was calculated for both groups and expressed as median total costs per patient per day alive . Because effectiveness aspects other than mortality are not incorporated in this ratio , other factors related to quality of life were used as qualitative measures of cost-effectiveness . The cost-effectiveness ratios were $ 63 and $ 94 for the early ICD and EP-guided strategy groups , respectively , per patient per day alive . This amounts to a net cost-effectiveness of $ 11,315 per patient per year alive saved by early ICD implantation . Costs in the early ICD group were higher only during the first 3 months of follow-up , but as a result of the high proportion of therapy changes , including arrhythmia surgery and late ICD implantation , costs in the EP-guided strategy group became higher after that . Patients discharged with antiarrhythmic drugs as sole therapy had the lowest total costs . This subset , however , showed extremely high mortality , result ing in a poor cost-effectiveness ratio ( $ 196 per day ) . Invasive therapies and hospitalization were the major contributors to costs . If quality -of-life measures are taken into account , the cost-effectiveness of early ICD implantation was even more favorable . Recurrent cardiac arrest and cardiac transplantation occurred in the EP-guided strategy group only , whereas exercise tolerance , total hospitalization duration , number of invasive procedures , and antiarrhythmic therapy changes were significantly in favor of early ICD implantation . CONCLUSIONS In terms of cost-effectiveness , early ICD implantation is superior to the EP-guided therapeutic strategy in postinfa rct sudden death survivors METHODS : Over the course of five years , 196 patients in New York Heart Association functional class I , II , or III with prior myocardial infa rct ion ; a left ventricular ejection fraction < or = 0.35 ; a documented episode of asymptomatic unsustained ventricular tachycardia ; and inducible , nonsuppressible ventricular tachyarrhythmia on electrophysiologic study were r and omly assigned to receive an implanted defibrillator ( n = 95 ) or conventional medical therapy ( n=101 ) . We used a two-sided sequential design with death from any cause as the end point BACKGROUND Unsustained ventricular tachycardia in patients with previous myocardial infa rct ion and left ventricular dysfunction is associated with a two-year mortality rate of about 30 percent . We studied whether prophylactic therapy with an implanted cardioverter-defibrillator , as compared with conventional medical therapy , would improve survival in this high-risk group of patients . METHODS Over the course of five years , 196 patients in New York Heart Association functional class I , II , or III with prior myocardial infa rct ion ; a left ventricular ejection fraction < or = 0.35 ; a documented episode of asymptomatic unsustained ventricular tachycardia ; and inducible , nonsuppressible ventricular tachyarrhythmia on electrophysiologic study were r and omly assigned to receive an implanted defibrillator ( n = 95 ) or conventional medical therapy ( n=101 ) . We used a two-sided sequential design with death from any cause as the end point . RESULTS The base-line characteristics of the two treatment groups were similar . During an average follow-up of 27 months , there were 15 deaths in the defibrillator group ( 11 from cardiac causes ) and 39 deaths in the conventional-therapy group ( 27 from cardiac causes ) ( hazard ratio for overall mortality , 0.46 ; 95 percent confidence interval , 0.26 to 0.82 ; P=0.009 ) . There was no evidence that amiodarone , beta-blockers , or any other antiarrhythmic therapy had a significant influence on the observed hazard ratio . CONCLUSIONS In patients with a prior myocardial infa rct ion who are at high risk for ventricular tachyarrhythmia , prophylactic therapy with an implanted defibrillator leads to improved survival as compared with conventional medical therapy BACKGROUND Implantable cardioverter-defibrillator ( ICD ) therapy significantly prolongs life in patients at increased risk for sudden death from depressed left ventricular function . However , whether this increased longevity is accompanied by deterioration in the quality of life is unclear . METHODS In a r and omized trial , we compared ICD therapy or amiodarone with state-of-the-art medical therapy alone in 2521 patients who had stable heart failure with depressed left ventricular function . We prospect ively measured quality of life at baseline and at months 3 , 12 , and 30 ; data collection was 93 to 98 % complete . The Duke Activity Status Index ( which measures cardiac physical functioning ) and the Medical Outcomes Study 36-Item Short-Form Mental Health Inventory 5 ( which measures psychological well-being ) were prespecified primary outcomes . Multiple additional quality -of-life outcomes were also examined . RESULTS Psychological well-being in the ICD group , as compared with medical therapy alone , was significantly improved at 3 months ( P=0.01 ) and at 12 months ( P=0.003 ) but not at 30 months . No clinical ly or statistically significant differences in physical functioning among the study groups were observed . Additional quality -of-life measures were improved in the ICD group at 3 months , 12 months , or both , but there was no significant difference at 30 months . ICD shocks in the month preceding a scheduled assessment were associated with a decreased quality of life in multiple domains . The use of amiodarone had no significant effects on the primary quality -of-life outcomes . CONCLUSIONS In a large primary -prevention population with moderately symptomatic heart failure , single-lead ICD therapy was not associated with any detectable adverse quality -of-life effects during 30 months of follow-up |
13,503 | 21,273,902 | Results suggest that knee braces and foot orthoses are effective in decreasing pain , joint stiffness , and drug dosage .
They also improve proprioception , balance , Kellgren/Lawrence grading , and physical function scores in subjects with varus and valgus knee osteoarthritis .
Knee braces and foot orthoses could be cautiously considered as conservative management for relief of pain and stiffness and improving physical function for persons with knee osteoarthritis . | null | null |
13,504 | 22,072,093 | Conclusions The findings do not support the notion that the treatment effects of exercise therapy in cLBP are directly attributable to changes in the musculoskeletal system . | Introduction The effect size for exercise therapy in the treatment of chronic non-specific low back pain ( cLBP ) is only modest .
This review aims to analyse the specificity of the effect by examining the relationship between the changes in clinical outcome ( pain , disability ) and the changes in the targeted aspects of physical function ( muscle strength , mobility , muscular endurance ) after exercise therapy . | 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 Study Design . A r and omized controlled trial with a 6-month follow-up period was conducted . Objective . To compare lumbar extension exercise and whole-body vibration exercise for chronic lower back pain . Summary of Background Data . Chronic lower back pain involves muscular as well as connective and neural systems . Different types of physiotherapy are applied for its treatment . Industrial vibration is regarded as a risk factor . Recently , vibration exercise has been developed as a new type of physiotherapy . It is thought to activate muscles via reflexes . Methods . In this study , 60 patients with chronic lower back pain devoid of “ specific ” spine diseases , who had a mean age of 51.7 years and a pain history of 13.1 years , practice d either isodynamic lumbar extension or vibration exercise for 3 months . Outcome measures were lumbar extension torque , pain sensation ( visual analog scale ) , and pain-related disability ( pain disability index ) . Results . A significant and comparable reduction in pain sensation and pain-related disability was observed in both groups . Lumbar extension torque increased significantly in the vibration exercise group ( 30.1 Nm/kg ) , but significantly more in the lumbar extension group ( + 59.2 Nm/kg ; SEM 10.2;P < 0.05 ) . No correlation was found between gain in lumbar torque and pain relief or pain-related disability ( P > 0.2 ) . Conclusions . The current data indicate that poor lumbar muscle force probably is not the exclusive cause of chronic lower back pain . Different types of exercise therapy tend to yield comparable results . Interestingly , well-controlled vibration may be the cure rather than the cause of lower back pain OBJECTIVE Recent evidence suggests that fibromyalgia is a disorder characterized by dysfunctional brain activity . Because transcranial direct current stimulation ( tDCS ) can modulate brain activity noninvasively and can decrease pain in patients with refractory central pain , we hypothesized that tDCS treatment would result in pain relief in patients with fibromyalgia . METHODS Thirty-two patients were r and omized to receive sham stimulation or real tDCS with the anode centered over the primary motor cortex ( M1 ) or the dorsolateral prefrontal cortex ( DLPFC ) ( 2 mA for 20 minutes on 5 consecutive days ) . A blinded evaluator rated the patient 's pain , using the visual analog scale for pain , the clinician 's global impression , the patient 's global assessment , and the number of tender points . Other symptoms of fibromyalgia were evaluated using the Fibromyalgia Impact Question naire and the Short Form 36 Health Survey . Safety was assessed with a battery of neuropsychological tests . To assess potential confounders , we measured mood and anxiety changes throughout the trial . RESULTS Anodal tDCS of the primary motor cortex induced significantly greater pain improvement compared with sham stimulation and stimulation of the DLPFC ( P < 0.0001 ) . Although this effect decreased after treatment ended , it was still significant after 3 weeks of followup ( P = 0.004 ) . A small positive impact on quality of life was observed among patients who received anodal M1 stimulation . This treatment was associated with a few mild adverse events , but the frequency of these events in the active-treatment groups was similar to that in the sham group . Cognitive changes were similar in all 3 treatment groups . CONCLUSION Our findings provide initial evidence of a beneficial effect of tDCS in fibromyalgia , thus encouraging further trials & NA ; Complex regional pain syndrome type 1 ( CRPS1 ) involves cortical abnormalities similar to those observed in phantom pain and after stroke . In those groups , treatment is aim ed at activation of cortical networks that subserve the affected limb , for example mirror therapy . However , mirror therapy is not effective for chronic CRPS1 , possibly because movement of the limb evokes intolerable pain . It was hypothesised that preceding mirror therapy with activation of cortical networks without limb movement would reduce pain and swelling in patients with chronic CRPS1 . Thirteen chronic CRPS1 patients were r and omly allocated to a motor imagery program ( MIP ) or to ongoing management . The MIP consisted of two weeks each of a h and laterality recognition task , imagined h and movements and mirror therapy . After 12 weeks , the control group was crossed‐over to MIP . There was a main effect of treatment group ( F(1,11)=57 , P<0.01 ) and an effect size of ∼25 points on the Neuropathic pain scale . The number needed to treat for a 50 % reduction in NPS score was ∼2 . The effect of treatment was replicated in the crossed‐over control subjects . The results uphold the hypothesis that a MIP initially not involving limb movement is effective for CRPS1 and support the involvement of cortical abnormalities in the development of this disorder . Although the mechanisms of effect of the MIP are not clear , possible explanations are sequential activation of cortical pre‐motor and motor networks , or sustained and focussed attention on the affected limb , or both & NA ; In complex regional pain syndrome ( CRPS1 ) initiated by wrist fracture , a motor imagery program ( MIP ) , consisting of h and laterality recognition followed by imagined movements and then mirror movements , reduces pain and disability , but the mechanism of effect is unclear . Possibilities include sustained attention to the affected limb , in which case the order of MIP components would not alter the effect , and sequential activation of cortical motor networks , in which case it would . Twenty subjects with chronic CRPS1 initiated by wrist fracture and who satisfied stringent inclusion criteria , were r and omly allocated to one of three groups : h and laterality recognition , imagined movements , mirror movements ( RecImMir , MIP ) ; imagined movements , recognition , imagined movements ( ImRecIm ) ; recognition , mirror movements , recognition ( RecMirRec ) . At 6 and 18 weeks , reduced pain and disability were greater for the RecImMir group than for the other groups ( P<0.05 ) . H and laterality recognition imparted a consistent reduction in pain and disability across groups , however , this effect was limited in magnitude . Imagined movements imparted a further reduction in pain and disability , but only if they followed h and laterality recognition . Mirror movements also imparted a reduction in pain and disability , but only when they followed imagined movements . The effect of the MIP seems to be dependent on the order of components , which suggests that it is not due to sustained attention to the affected limb , but is consistent with sequential activation of cortical motor networks OBJECTIVES We have previously reported in two r and omized controlled trials that cognitive intervention and exercises more effectively improved isokinetic trunk muscle strength than lumbar fusion and postoperative rehabilitation in patients with chronic low back pain . The aim of the present study was to predict changes in muscle strength as regard to changes in pain , function , fear-avoidance beliefs ( self-rated question naires ) , changes in cross-sectional area and density of the back muscles and treatment . METHODS We assessed 1 ) isokinetic trunk muscle strength ; 2 ) cross-sectional area and density of back muscles by computer-tomography ( CT ) ; and 3 ) pain , function , fear-avoidance beliefs , and self- efficacy for pain in the included patients at baseline and 1-year follow-up . Multiple regression analysis was performed with change in muscle strength as dependent variables , and changes in area/density and self-rated symptoms and treatment as independent variables . RESULTS The correlations between the change in muscle strength and change in both cross-sectional area and density were weak ( r < 0.1 ) and nonsignificant and these variables were not included in the multiple regression analysis . The change in pain , change in fear-avoidance beliefs , change in self-efficacy for pain and treatment explained 46 % of the change in muscle strength , with change in pain and treatment as significant predictors . CONCLUSION Our results emphasize the central role of pain and treatment for the improvements in muscle strength in patients with chronic low back pain Abstract Practice guidelines recommend various types of exercise and manipulative therapy for chronic back pain but there have been few head‐to‐head comparisons of these interventions . We conducted a r and omized controlled trial to compare effects of general exercise , motor control exercise and manipulative therapy on function and perceived effect of intervention in patients with chronic back pain . Two hundred and forty adults with non‐specific low back pain ⩾3 months were allocated to groups that received 8 weeks of general exercise , motor control exercise or spinal manipulative therapy . General exercise included strengthening , stretching and aerobic exercises . Motor control exercise involved retraining specific trunk muscles using ultrasound feedback . Spinal manipulative therapy included joint mobilization and manipulation . Primary outcomes were patient‐specific function ( PSFS , 3–30 ) and global perceived effect ( GPE , −5 to 5 ) at 8 weeks . These outcomes were also measured at 6 and 12 months . Follow‐up was 93 % at 8 weeks and 88 % at 6 and 12 months . The motor control exercise group had slightly better outcomes than the general exercise group at 8 weeks ( between‐group difference : PSFS 2.9 , 95 % CI : 0.9–4.8 ; GPE 1.7 , 95 % CI : 0.9–2.4 ) , as did the spinal manipulative therapy group ( PSFS 2.3 , 95 % CI : 0.4–4.2 ; GPE 1.2 , 95 % CI : 0.4–2.0 ) . The groups had similar outcomes at 6 and 12 months . Motor control exercise and spinal manipulative therapy produce slightly better short‐term function and perceptions of effect than general exercise , but not better medium or long‐term effects , in patients with chronic non‐specific back pain Many manual therapists assess and treat spinal stiffness of people with low back pain . The objectives of this study were to investigate : ( i ) whether spinal stiffness changes after treatment ; ( ii ) the relationship between pre-treatment spinal stiffness and change in stiffness with treatment ; ( iii ) the relationship between spinal stiffness , pain , disability and global perceived effect of treatment ; ( iv ) whether spinal stiffness predicts outcome of treatment or response to treatment in chronic low back pain patients . One hundred and ninety-one subjects with chronic low back pain were r and omly allocated to groups that received either spinal manipulative therapy , motor control exercise , or a general exercise program . Spinal stiffness was assessed before and after intervention . All three groups showed a significant decrease in stiffness following treatment ( p<0.001 ) . No difference between groups was observed . There was a significant negative correlation between pre-treatment stiffness and change in stiffness ( r=-0.61 ; p<0.001 ) . There was a significant but weak correlation ( r=0.18 ; p=0.02 ) between change in stiffness and change in global perceived effect of treatment , and a significant but weak correlation between change in stiffness and change in function for subjects in the spinal manipulative therapy group ( r=-0.28 ; p=0.02 ) . No significant association was observed between initial stiffness score and any of the final outcome measures following treatment . Initial stiffness did not predict response to any treatment . In conclusion , spinal stiffness decreases over the course of an episode of treatment , more so in those with the stiffest spines , but the decrease is not dependent on treatment and is not generally related to outcome Design . R and omized prospect i ve study of the effects of three types of active therapy on back muscle function in chronic low back pain patients . Objectives . To quantify the effects of 3 months active therapy on strength , endurance , activation , and fatigability of the back entensor muscles . Summary of Background Data . Many studies have documented an association between chronic low back pain and diminished muscular performance capacity . Few studies have quantified the changes in these measures following interventions using objective measurement techniques or related them to changes in clinical outcome . Methods . A total of 148 individuals ( 57 % women ) with chronic low back pain ( age , 45.0 ± 10.0 years ; duration of low back pain , 10.9 ± 9.5 years ) were r and omized to a treatment that they attended for 3 months : active physiotherapy , muscle reconditioning on devices , or low-impact aerobics . Before and after therapy , assessment s were made of the following : trunk muscle strength ( in flexion , extension , lateral bending , and axial rotation ) , erector spinae activation ( maximal , and during forward bending movements ) , back extensor endurance ( Biering-S/orensen test ) , and erector spinae fatigability ( determined from changes in the median frequency of the surface electromyographic signal ) during isometric and dynamic tests . Results . A total of 132 of 148 patients ( 89 % ) completed the therapy . Isometric strength in each movement direction increased in all groups post-therapy ( P < 0.0008 ) , most notably in the devices group . Activation of the erector spinae during the extension tests also increased significantly in all groups and showed a weak , but significant , relationship with increased maximal strength ( P = 0.01 ) . Pretherapy 55 % of the subjects showed no relaxation of the back muscles at L5 when in the fully flexed position ; no changes were observed in any group post-therapy . Endurance time during the Biering-S/orensen test increased significantly post-therapy in all groups ( P = 0.0001 ) , but there were no significant changes in EMG-determined fatigability . Fatigability of the lumbar muscles at L5 ( EMG median frequency changes ) during the dynamic test increased post-therapy ( P = 0.0001 ) without group differences . Conclusion . Significant changes in muscle performance were observed in all three active therapy groups post-therapy , which appeared to be mainly due to changes in neural activation of the lumbar muscles and psychological changes concerning , for example , motivation or pain tolerance STUDY DESIGN A r and omized clinical trial . OBJECTIVES To examine the relative efficacy of three active therapies for chronic low back pain . SUMMARY OF BACKGROUND DATA There is much evidence documenting the efficacy of exercise in the conservative management of chronic low back pain , but many questions remain regarding its exact prescription and method of application . The most successful method must be identified to enable refinement of future rehabilitation programs to target the specific needs of the patient with chronic low back pain and the budget of the healthcare provider . METHODS One hundred forty-eight patients with chronic low back pain were r and omized to one of the following treatments , which they attended twice a week for 3 months : 1 ) modern active physiotherapy , 2 ) muscle reconditioning on training devices , or 3 ) low-impact aerobics . Pretherapy and posttherapy , objective measurements of lumbar mobility were performed , and question naires were administered inquiring about self-rated pain and disability , and psychosocial factors . Similar question naires were administered 6 months after therapy . The data were analyzed using the intention-to-treat principle . RESULTS Of the 148 patients , 16 ( 10.8 % ) dropped out of the therapy . One hundred thirty-seven question naires ( 93 % ) were available for analysis at all three time points . After therapy , significant reductions were observed in pain intensity , frequency , and disability ; Fear-Avoidance Beliefs about physical activity ( FABQactivity ) ; and " praying/hoping , " " catastrophizing , " and " pain behavior " coping strategies -- each with no group differences in the extent of the response . These effects were maintained over the subsequent 6 months , with the exception of disability and FABQactivity for the physiotherapy group . There were small but significant posttherapy increases in lumbar mobility , with aerobics and devices showing a greater response than physiotherapy . CONCLUSION The general lack of treatment specificity suggests that the main effects of the therapies were educed not through the reversal of physical weaknesses targeted by the corresponding exercise modality , but rather through some " central " effect , perhaps involving an adjustment of perception in relation to pain and disability . The direct costs associated with administering physiotherapy were three times as great , and devices four times as great , as those for aerobics . Administration of aerobics as an efficacious therapy for chronic low back pain has the potential to relieve some of the huge financial burden associated with the condition BACKGROUND Low back disorders are a prevalent problem in society today and may lead to chronic debilitating low back pain . Developing our underst and ing of temporal muscle and kinematic patterns during manual material h and ling tasks may provide insight for preventing the cascading series of events leading to chronic low back pain . METHODS Sixty-two low back pain patients and 61 asymptomatic participants performed a variety of lifting exertions that varied in lift origin horizontal and vertical distance , lift asymmetry , and weight . Electromyographic activity of 10 trunk muscles as well as trunk and pelvic kinematics was recorded during each exertion . Differences in muscle activation and kinematic parameters were compared between low back pain patients and asymptomatic participants as a function of experimental conditions . FINDINGS Both the left and right erector spinae activated significantly earlier and were on significantly longer in low back pain patients compared to asymptomatic participants . The horizontal and vertical location of the lift influenced the EMG and kinematic differences between the low back pain patients and asymptomatic participants . INTERPRETATION These finding indicate that low back pain patients would be exposed to increase muscle activity result ing in higher spine loads for a greater length of time compared to asymptomatic participants . The longer exposure time to increased spine load may lead to greater risk of future low back injury and cascading events leading to debilitating low back pain . The longer muscle activation time suggests that low back pain patients have changed their motor program from an open to a closed loop system The major objective of this investigation was to study the effectiveness of the physical conditioning program used at the University of Miami Comprehensive Pain and Rehabilitation Center in restoring certain elements of the functional abilities of individuals suffering from chronic low-back pain and to evaluate the effectiveness of using a systematic ally applied , aggressive stretching maneuver as an add-on therapy in the treatment of chronic low-back pain patients . The effect(s ) of the proposed stretching maneuver was evaluated . Twenty-eight chronic low-back pain patients were r and omly assigned to one of two groups . The control group underwent a multimodal rehabilitation program , and the experimental group underwent the same rehabilitation program in addition to the systematic stretching maneuver under investigation . The results obtained showed that patients undergoing the multimodal rehabilitation program with and without the proposed systematic stretching maneuver showed a significant improvement in their functional abilities as seen from the significant increase in the static strength of the back extensors , with corresponding significant increase in back muscle myoelectric signals . Also , a significant decrease in their pain level was reported after 2 weeks of continuous treatment . The use of the systematic stretching maneuver enhanced the functional gains of chronic low-back pain patients compared to the control group The aim of this study was to determine whether grade d activity restored occupational function in industrial blue-collar workers who were sick-listed for 8 weeks because of subacute , nonspecific , mechanical low back pain ( LBP ) . Patients with LBP , who had been examined by an orthopedic surgeon and a social worker , were r and omly assigned to either an activity group ( n = 51 ) or a control group ( n = 52 ) . Patients with defined orthopedic , medical , or psychiatric diagnoses were excluded before r and omization . The grade d activity program consisted of four parts : ( 1 ) measurements of functional capacity ; ( 2 ) a work-place visit ; ( 3 ) back school education ; and ( 4 ) an individual , submaximal , gradually increased exercise program , with an operant-conditioning behavioral approach , based on the results of the tests and the dem and s of the patient 's work . Records of the amount of sick leave taken over a 3-year period ( ie , the 1-year periods before , during , and after intervention ) were obtained from each patient 's Social Insurance Office . The patients in the activity group returned to work significantly earlier than did the patients in the control group . The median number of physical therapist appointments before return to work was 5 , and the average number of appointments was 10.7 ( SD = 12.3 ) . The average duration of sick leave attributable to LBP during the second follow-up year was 12.1 weeks ( SD = 18.4 ) in the activity group and 19.6 weeks ( SD = 20.7 ) in the control group . Four patients in the control group and 1 patient in the activity group received permanent disability pensions . The grade d activity program made the patients occupationally functional again , as measured by return to work and significantly reduced long-term sick leave STUDY DESIGN Trunk angular motion features were used as a means to quantify the extent of a low back disorder in healthy people and patients with chronic low back disorders . OBJECTIVE To refine and vali date a previously reported means of quantifying the extent of a low back disorder . SUMMARY AND BACKGROUND Many assessment tools of low back disorder are subjective . A quantitative assessment tool would facilitate the tracking of the recovery and help document the appropriateness of treatments . METHODS The trunk motion characteristics of 374 healthy people and 335 patients with chronic low back disorders of varying severity were documented as they flexed and extended their trunks in five different planes of motion . The trunk motion features were normalized as a function of age and gender . Four classification techniques were used to assess the ability of the quantitative motion measure to identify those with and without low back disorders . In addition , 31 patients were observed longitudinally to determine whether the motion measures agreed with observed changes in back pain symptoms . RESULTS The quantitative trunk motion measure distinguished between people with low back disorders and healthy people between 88 % and 94 % of the time , depending on which classification system was used . Sensitivity and specificity varied between 83 % and 97 % . The quantitative measure also showed promise as a means to distinguish between muscle-based and structure-based low back disorders . Prospect i ve findings indicated that the quantification system agreed well with clinical observations of progress . CONCLUSIONS The quantification of trunk motion can serve as a measure of the extent of a low back disorder . When considered along with other clinical information , the ability to assess and treat low back disorders is enhanced The aim of this single-blind pilot RCT was to investigate the effect of pain biology education and group exercise classes compared to pain biology education alone for individuals with chronic low back pain ( CLBP ) . Participants with CLBP were r and omised to a pain biology education and group exercise classes group ( EDEX ) [ n = 20 ] or a pain biology education only group ( ED ) [ n = 18 ] . The primary outcome was pain ( 0 - 100 numerical rating scale ) , and self-reported function assessed using the Rol and Morris Disability Question naire , measured at pre-intervention , post-intervention and three month follow up . Secondary outcome measures were pain self-efficacy , pain related fear , physical performance testing and free-living activity monitoring . Using a linear mixed model analysis , there was a statistically significant interaction effect between time and intervention for both pain ( F[2,49 ] = 3.975 , p < 0.05 ) and pain self-efficacy ( F[2,51 ] = 4.011 , p < 0.05 ) with more favourable results for the ED group . The effects levelled off at the three month follow up point . In the short term , pain biology education alone was more effective for pain and pain self-efficacy than a combination of pain biology education and group exercise classes . This pilot study highlights the need to investigate the combined effects of different interventions 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 Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists OBJECTIVE : To 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 Different training models are effective for the treatment of chronic low back pain , but no consensus has been found . Earlier studies have emphasized training of spinal mobility and back strength . To evaluate if other physiological parameters , such as coordination , are of equal importance , we performed a r and omized trial on 40 consecutive patients with chronic low back pain . Two training models were compared : 1 ) intensive training of muscle endurance and 2 ) muscle training , including coordination . In both groups , training was performed 1 hour twice a week for 3 months . Pain score , disability score , and spinal mobility improved in both training groups without differences between the two groups . Only intensive training of muscle endurance improved isokinetic back muscle strength . At study entry , we found a significant correlation between spinal mobility and dysfunction , but after the training , no correlation was found between improvement of spinal mobility or isokinetic back extension strength and improvement of function or pain level . We conclude that coordination training for patients with chronic low back pain is as equally effective as endurance training OBJECTIVE To compare the short-term outcomes of active individual therapy ( AIT ) with those of a functional restoration program ( FRP ) . DESIGN Prospect i ve r and omized controlled study . SETTING Two rehabilitation centers and private ambulatory physiotherapy facilities . PARTICIPANTS One hundred thirty-two adults with chronic low back pain . Fifty-one percent of patients on sick leave or out of work ( mean duration , 180d in the 2y before treatment ) . INTERVENTIONS For 5 weeks , FRP ( at 25h/wk ) or AIT ( at 3h/wk ) . MAIN OUTCOME MEASURES Trunk flexibility , back flexor , and extensor endurance ( Ito and Sorensen tests ) , general endurance , pain intensity , Dallas Pain Question naire ( DPQ ) scores , daily activities , anxiety depression , social interest , and work and leisure activities , and self-reported improvement ( work ability , resumption of sport and leisure activities ) . RESULTS All outcome measures improved after treatment except endurance in AIT . There was no between-group difference for pain intensity or DPQ daily activities or work and leisure activities scores . Better results were observed in FRP for all other outcome measures . There was a significant effect of treatment and the initial value for the gain of the Sorensen score with a treatment or initial value interaction ; a significant effect of treatment and initial value on the gains of Ito , endurance , and DPQ social interest and anxiety depression scores , with no treatment or initial value interaction ; and a significant effect of initial value but not treatment for the gains of DPQ daily activities and work and leisure activities scores . CONCLUSIONS Low-cost ambulatory AIT is effective . The main advantage of FRP is improved endurance . We speculate that this may be linked to better self-reported work ability and more frequent resumption of sports and leisure activities Kell , RT , and Asmundson , GJG . A comparison of two forms of periodized exercise rehabilitation programs in the management of chronic nonspecific low-back pain . J Strength Cond Res 23(2 ) : 513 - 523 , 2009-The purpose of this study was to determine the influence of 2 different periodized exercise rehabilitation programs ( resistance training [ RT ] and aerobic training [ AT ] ) on musculoskeletal health , body composition , pain , disability , and quality of life ( QOL ) in chronic ( ≥3 months ; ≥3 d·wk−1 ) nonspecific low-back pain ( CLBP ) persons . Twenty-seven CLBP subjects were r and omly assigned to 1 of 3 groups , 1 ) RT ( n = 9 ) , 2 ) AT ( n = 9 ) , or 3 ) control ( C ; n = 9 ) . Subjects were tested at baseline and at weeks 8 and 16 of training . Intensity and volume were periodized in the training groups . Significance was set at p ≤ 0.05 . No significant differences were noted among the groups at baseline . The RT group significantly decreased body fat percent from baseline to week 8 and from baseline to week 16 , whereas the AT group significantly decreased body fat percent and body mass from baseline to week 16 . The RT group significantly improved most musculoskeletal fitness , pain , disability , and QOL outcomes from baseline to week 8 , baseline to week 16 , and weeks 8 to 16 . However , the AT group showed significant improvements in flexibility from baseline to week 8 and in cardiorespiratory and peak leg power from baseline to week 8 and baseline to week 16 . The AT groups showed no significant improvements in pain , disability , or QOL . The primary finding was that periodized RT was successful at improving many fitness , pain , disability , and QOL outcome measures , whereas AT was not . This study indicates that whole-body periodized RT can be used by training and conditioning personnel in the rehabilitation of those clients suffering with CLBP 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 Study Design . A r and omized study . Objectives . To compare muscle strength , cross-sectional area , and density of the back muscles in two categories of patients with chronic low back pain , r and omized to either lumbar fusion or cognitive intervention and exercises . Summary of Background Data . In two clinical trials , patients with chronic low back pain plus disc degeneration and postlaminectomy syndrome , respectively , were r and omized to either lumbar fusion or cognitive intervention and exercises . We have previously reported that results for the primary outcome were similar at the 1-year follow-up examination . Methods . As the treatment alternatives and test procedures were identical , the two trials were merged into one . A total of 124 patients 25 to 60 years of age were included . Muscle strength , measured by isokinetic test device and by the Biering-Sørensen Test , was measured in 112 patients , and the cross-sectional area and density of the back muscles were measured in 61 patients at the inclusion and at the 1-year follow-up examination . Results . The exercise group performed significantly better in muscle strength than did the lumbar fusion group , with the mean difference at 184 Nm ( 95 % confidence interval , 64–303 Nm ; P = 0.003 ) and for the Biering-Sørensen Test 21 seconds ( 95 % confidence interval , 6–36 seconds ; P = 0.006 ) . The density at L3–L4 decreased in the lumbar fusion group but remained unchanged in the exercise group . The mean difference was 5.3 HU ( 95 % confidence interval , 1.1–9.5 HU ; P = 0.01 ) . The cross-sectional area was unchanged in both groups . Conclusions . Patients with chronic low back pain who followed cognitive intervention and exercise programs improved significantly in muscle strength compared with patients who underwent lumbar fusion . In the lumbar fusion group , density decreased significantly at L3–L4 compared with the exercise group Abstract There is overlap between brain regions involved in taste and pain perception , and cortical injuries may lead to increases as well as decreases in sensitivity to taste . Recently it was shown that chronic back pain ( CBP ) is associated with a specific pattern of brain atrophy . Since CBP is characterized by increased sensitivity to pain , we reasoned that the sense of taste might also be enhanced in CBP . Detection and recognition thresholds were established for a sour taste and ratings of both suprathreshold taste intensity and pleasantness – unpleasantness perception were collected for sweet , sour , salty and bitter stimuli in 11 CBP patients and 11 matched control subjects . As a control , ratings were also collected for visual assessment of degree of grayness . There was no difference between CBP and control subjects for visual grayness rating . On the other h and , CBP patients in comparison to control subjects rated gustatory stimuli as significantly more intense but no more or less pleasant and showed a trend towards a lower detection threshold ( i.e. increased sensitivity ) . The selectivity of the taste disturbance suggests interaction between pain and taste at specific brain sites and provides further evidence that CBP involves specific brain abnormalities OBJECTIVE To investigate the effects of 21 weeks ' progressive strength training on neuromuscular function and subjectively perceived symptoms in premenopausal women with fibromyalgia ( FM ) . METHODS Twenty one women with FM were r and omly assigned to experimental ( FMT ) or control ( FMC ) groups . Twelve healthy women served as training controls ( HT ) . The FMT and HT groups carried out progressive strength training twice a week for 21 weeks . The major outcome measures were muscle strength and electromyographic ( EMG ) recordings . Secondary outcome measures were pain , sleep , fatigue , physical function capacity ( Stanford Health Assessment Question naire ) , and mood ( short version of Beck 's depression index ) . RESULTS Female FMT subjects increased their maximal and explosive strength and EMG activity to the same extent as the HT group . Moreover , the progressive strength training showed immediate benefits on subjectively perceived fatigue , depression , and neck pain of training patients with FM . CONCLUSIONS The strength training data indicate comparable trainability of the neuromuscular system of women with FM and healthy women . Progressive strength training can safely be used in the treatment of FM to decrease the impact of the syndrome on the neuromuscular system , perceived symptoms , and functional capacity . These results confirm the opinion that FM syndrome has a central rather than a peripheral or muscular basis OBJECTIVE To assess the efficacy and treatment compliance of a home-based rehabilitation programme for chronic low back pain ( CLBP ) . POPULATION CLBP out patients treated in a Physical Medicine Rehabilitation or Rheumatology unit within a university hospital . METHODS We performed a prospect i ve , comparative study . The participants were r and omly assigned to either a home-based rehabilitation programme ( Gp A ) or a st and ard physical therapy ( Gp B ) . The programme included four weekly sessions . In each group , we measured pain intensity ( on a visual analogue scale , VAS ) , flexibility and muscle endurance ( the Schöber MacRae test , finger-to-floor distance , thigh-leg angle , the Shirado and Sorensen test ) , functional and psychological repercussions ( the Quebec functional index and the Hospital Anxiety and Depression scale ) and h and icap ( on a VAS ) . Follow-up examinations took place at baseline and four weeks and three , six and 12 months later . RESULTS One hundred and seven patients ( 82 women ) with a mean+/-st and ard deviation ( S.D. ) age of 35.7+/-0.8 years were included ( with 54 patients in Gp A ) . At four weeks , a significant improvement ( relative to baseline ) was observed for all parameters in both study groups but with a significantly greater difference in Gp A , which was maintained at one year ( despite an observed regression of the improvement at six months ) . At one year , compliance with the home-based rehabilitation programme was good ( 68.1 % ) and 59.5 % of the patients regarded the programme as useful . CONCLUSION Our results suggest that a home-based rehabilitation programme is as effective as st and ard physical therapy . However , this type of programme requires patient motivation and regular follow-up STUDY DESIGN A r and omized study comparing the results of active rehabilitation and passive control treatment in patients with chronic low back pain with follow-up at 6 months and 1 year . OBJECTIVES To study the efficacy of active rehabilitation on pain , self-experienced disability , and lumbar fatigability . SUMMARY OF BACKGROUND DATA Exercises in an outpatient setting are widely used for the treatment of chronic low back pain . The efficacy of the active rehabilitation approach has been documented in r and omized control studies , but these studies have seldom been focused on lumbar fatigability , which is now recognized as a frequent problem among patients with chronic low back pain . METHODS Fifty-nine middle-aged patients ( 37 men and 22 women ) with nonspecific chronic low back pain were r and omly assigned to 12 weeks ' active rehabilitation or to a passive control treatment ( massage , thermal therapy ) . Pain and disability index , low back pain intensity ( visual analog scale , 100 mm ) , and the objective ly assessed lumbar muscle fatigability ( spectral electromyogram , mean power frequency slope [ MPFSLOPE ] ) in a new 90-second submaximal isoinertial back endurance test were recorded before and after the interventions and at 6-month and 1-year follow-up visits . RESULTS Results of repeated measures multivariate analysis of variance indicated that back pain intensity ( visual analog scale ) and functional disability ( pain and disability index score ) decreased , and lumbar endurance ( MPFSLOPE ) improved significantly more ( P < 0.05 ) in the active rehabilitation group than in the passive control treatment group , when measured at a 1-year follow-up examination . The group difference in visual analog scale and pain and disability index changes became even more significant at the end of 1 year . The change in lumbar endurance was significantly greater in the active rehabilitation group than in the passive control treatment group at the 6-month follow-up , but not at the 1-year follow-up . CONCLUSIONS The active progressive treatment program was more successful in reducing pain and self-experienced disability and also in improving lumbar endurance than was the passive control treatment . However , the group difference in lumbar endurance tended to diminish at the 1-year follow-up OBJECTIVES To determine the effect of a series of electro-acupuncture ( EA ) treatment in conjunction with exercise on the pain , disability , and functional improvement scores of patients with chronic low-back pain ( LBP ) . DESIGN A blinded prospect i ve r and omized controlled study . SUBJECTS AND INTERVENTIONS A total of 52 patients were r and omly allocated to an exercise group ( n = 26 ) or an exercise plus EA group ( n = 26 ) and treated for 12 sessions . OUTCOME MEASURES Numerical Rating Scale ( NRS ) , Aberdeen LBP scale , lumbar spinal active range of movement ( AROM ) , and the isokinetic strength were assessed by a blinded observer . Repeated measures analysis of variance ( R-ANOVA ) with factors of group and time was used to compare the outcomes between the two groups at baseline ( before treatment ) , immediately after treatment , 1-month follow-up , and 3-month follow-up . The level of significance was set at p = 0.05 . RESULTS Significantly better scores in the NRS and Aberdeen LBP scale were found in the exercise plus EA group immediately after treatment and at 1-month follow-up . Higher scores were also seen at 3-month follow-up . No significant differences were observed in spinal AROM and isokinetic trunk concentric strength between the two groups at any stage of follow-up . CONCLUSIONS This study provides additional data on the potential role of EA in the treatment of LBP , and indicates that the combination of EA and back exercise might be an effective option in the treatment of pain and disability associated with chronic LBP BACKGROUND AND PURPOSE Improving functional performance in patients with chronic low back pain is of primary importance . The purpose of this study was to examine the effects of 2 proprioceptive neuromuscular facilitation ( PNF ) programs on trunk muscle endurance , flexibility , and functional performance in subjects with chronic low back pain ( CLBP ) . SUBJECTS Eighty-six women ( 40.2+/-11.9 [ mean+/-SD ] years of age ) who had complaints of CLBP were r and omly assigned to 3 groups : rhythmic stabilization training , combination of isotonic exercises , and control . METHODS Subjects trained with each program for 4 weeks with the aim of improving trunk stability and strength . Static and dynamic trunk muscle endurance and lumbar mobility were measured before , at the end of , and 4 and 8 weeks after training . Disability and back pain intensity also were measured with the Oswestry Index . RESULTS Multivariate analysis of variance indicated that both training groups demonstrated significant improvements in lumbar mobility ( 8.6%-24.1 % ) , static and dynamic muscle endurance ( 23.6%-81 % ) , and Oswestry Index ( 29.3%-31.8 % ) measurements . DISCUSSION AND CONCLUSION Static and dynamic PNF programs may be appropriate for improving short-term trunk muscle endurance and trunk mobility in people with CLBP Two-person or team lifting is a popular method for h and ling material s under awkward or heavy lifting conditions . While many guidelines and st and ards address safe lifting limits for individual lifting , there are no such limits for team lifting , and these lifts are poorly understood . The literature associated with team lifting offers some interesting paradoxes . Many studies have indicated that people lift less per individual under team conditions compared with one-person lifting . Yet , at least one study has reported an increase in team-lifting capacity when subjects were height-matched . The current study explored the spine loading characteristics of one- and two-person lifting teams when subjects lifted under several sagittally symmetric and asymmetric conditions . Spine compression was lower for two person lifts for a given weight , while lifting in sagittally symmetric conditions whereas lateral shear became much greater for two-person lifts under asymmetric lifting conditions . This study has linked these changes to differences in trunk kinematic patterns adopted during one- versus two-person lifting & NA ; The processing of pain‐related , body‐related and neutral words was assessed in chronic pain patients and matched healthy controls . During and after word presentation at perception threshold , electromyographic activity ( EMG ) , heart rate , skin conductance level and electroencephalographic ( EEG ) data from 11 electrode sites were recorded . Startle responses were measured to suprathreshold word stimuli . Although the patients did not recognize more pain‐related words , they produced an enhanced left‐hemispheric N100 and N200 to pain‐related as compared to neutral words . In addition , the patients did not show a distinct P300 but a continuous positive shift to all words extending into the 800‐ms range . Skin conductance levels to the pain‐related words were also enhanced in patients only . These data partially support the notion of pain‐related implicit memory structures in the brain of chronic pain patients that may selectively draw attention to pain‐related stimuli and may thus enhance pain perception Design . Cross-sectional analysis of the factors influencing self-rated disability associated with chronic low back pain and prospect i ve study of the relationship between changes in each of these factors and in disability following active therapy . Objectives . To examine the relative influences of pain , psychological factors , and physiological factors on self-rated disability . Summary of Background Data . In chronic LBP , the interrelationship between physical impairment , pain , and disability is particularly complicated , due to the influence of various psychological factors and the lack of unequivocal methods for assessing impairment . Investigations using new “ belief ” question naires and “ sophisticated ” performance tests , which have shown promise as discriminating measures of impairment , may assist in clarifying the situation . Previous studies have rarely investigated all these factors simultaneously . Methods . One hundred forty-eight patients with cLBP completed question naires and underwent tests of mobility , strength , muscle activation , and fatigability , and ( in a subgroup ) erector spinae size and fiber size/type distribution . All measures were repeated after 3 months active therapy . Relationships between each factor and self-rated disability ( Rol and and Morris question naire ) at baseline , and between the changes in each factor and changes in disability following therapy , were examined . Results . Stepwise linear regression showed that the most significant predictors of disability at baseline were , in decreasing order of importance : pain ; psychological distress ; fear-avoidance beliefs ; muscle activation levels ; lumbar range of motion ; gender . Only changes in pain , psychological distress , and fear-avoidance beliefs significantly accounted for the changes in disability following therapy . Conclusion . A combination of pain , psychological and physiological factors was best able to predict baseline disability , although its decrease following therapy was determined only by reductions in pain and psychological variables . The active therapy programm — in addition to improving physical function — appeared capable of modifying important psychological factors , possibly as a result of the positive experience of completing the prescribed exercises without undue harm It has been estimated that one fourth to one half of all patients treated in physical therapy clinics suffer from low-back pain . The purpose of this study was to compare the effects of spinal flexion ( Group I ) and extension ( Group II ) exercises on low-back pain severity and thoracolumbar spinal mobility in chronic mechanical low-back pain patients . Both groups had significantly less low-back pain after treatment ( P < .10 ) . There was no significant difference , however , between the spinal flexion and extension exercises in reduction of low-back pain severity . The results indicated a significant difference between the groups in increasing the sagittal mobility ( P < .10 ) . The results did not indicate any significant difference between and within groups in increasing the coronal and transverse mobility of the thoracolumbar spine . Either the spinal flexion or extension exercises could be used to reduce chronic mechanical low-back pain severity , but the flexion exercises had an advantage in increasing the sagittal mobility within a short period of time INTRODUCTION Active treatments are advocated for the management of non-specific chronic low back pain ( CLBP ) , although few studies have documented the relative efficacy of differing types of programme . A number of the available treatments comprise exercise routines on specially design ed training machines , which are ostensibly better disposed to reverse the compromised trunk muscle function displayed by these patients than are ' free exercise ' programmes . However , in using these muscle-training programmes , the physiological or anatomical adaptations that might account for the improved performance are rarely investigated , let alone identified . This is an important issue , because if the ' newly-acquired strength ' is mostly specific to performance on the devices on which the patient has trained and been tested , and reflects the skill in executing these particular tasks , this will not necessarily assist the patient during performance of his/her everyday activities . The aims of the present study were ( 1 ) to quantify the changes in back muscle performance in chronic LBP patients following 3 months active therapy , and ( 2 ) to analyse the corresponding changes in activation and cross-sectional area of the paraspinal muscles . METHODS 148 individuals ( 57 % women ) with CLBP ( age 45.0+/-10.0 years ; duration of LBP 10.9+/-9.5 years ) were r and omised to a treatment which they attended 2/week for 3 months : active physiotherapy , muscle reconditioning on training devices , or low-impact aerobics . Pre- and post-therapy , assessment s were made of isometric trunk muscle strength in each plane of movement and of erector spinae activation ( using surface electromyography ) during back extension . In a sub-group of 56 patients , the cross-sectional area of the paravertebral muscles was determined using magnetic resonance imaging ( MRI ) . In all patients , self-rated pain intensity , pain frequency and disability were assessed before and after therapy . RESULTS 132/148 patients completed the therapy . Isometric strength in each movement plane increased significantly in all groups post-therapy . Apart from trunk extension , the changes were significantly greater in the devices group than in the other two groups ( Fig 1 ) . Activation of the paraspinal muscles during back extension also increased significantly in all groups ( Fig 2 ) and was weakly , but significantly ( r = 0.37 ; p = 0.0001 ) correlated with increased strength in back extension . Although , at baseline , highly significant correlations were observed between the size of the paraspinal muscles ( at L3/4 and at L4/5 ) and isometric back extension strength ( r=0.75 ; p < 0.0001 ) , post-training increases in strength were not accompanied by corresponding changes in muscle size . None of the improvements in strength showed any relationship with the clinical changes in pain and disability , regardless of whether the latter were examined on an individual basis or in relation to ' outcome groups ' . CONCLUSION The superior trunk strength shown by the devices group post-therapy was considered to be attributable , in part , to a ' learning effect ' , of the type often seen when training and testing are carried out on the same machines . These gains are considered to be mostly ' task-specific ' . However , part of the improvement in strength after active therapy ( in all groups ) also appeared to be due to an increased neural activation of the trunk muscles . These positive effects should be transferable to the performance of everyday activities for which the same muscles are employed , although the percentage improvement is probably not as high as the measured increase in strength might suggest . Possible roles for improved co-ordination and changes in motivation and /or pain tolerance after therapy can not be excluded . No differences in the clinical outcome were observed between the three therapy groups , and the changes in physical performance after therapy did not correlate with the clinical outcome . It is therefore question able whether strength measurements have any clinical significance in documenting the success of rehabilitation programmes , other than on a motivational basis . The results of the present study suggest that the value of supervised active therapy programmes does not reside in the reversal of specific muscular deficiencies , but rather in the provision of a source of confirmation/encouragement for the patient , that movement is not harmful , and a foundation upon which to further build . Whether the utilisation of specific training devices , or individual instruction , is necessary to elicit these particular effects is question able & NA ; Although chronic back pain is one of the most frequent reasons for permanent impairment in people under 65 , the neurobiological mechanisms of chronification remain vague . Evidence suggests that cortical reorganisation , so‐called functional plasticity , may play a role in chronic back pain patients . In the search for the structural counterpart of such functional changes in the CNS , we examined 18 patients suffering from chronic back pain with voxel‐based morphometry and compared them to 18 sex and age matched healthy controls . We found a significant decrease of gray matter in the brainstem and the somatosensory cortex . Correlation analysis of pain unpleasantness and the intensity of pain on the day of scanning revealed a strong negative correlation ( i.e. a decrease in gray matter with increasing unpleasantness/increasing intensity of pain ) in these areas . Additionally , we found a significant increase in gray matter bilaterally in the basal ganglia and the left thalamus . These data support the hypothesis that ongoing nociception is associated with cortical and subcortical reorganisation on a structural level , which may play an important role in the process of the chronification of pain There is growing evidence for the idea that in back pain patients , pain-related fear ( fear of pain/physical activity/(re)injury ) may be more disabling than pain itself . A number of question naires have been developed to quantify pain-related fears , including the Fear-Avoidance Beliefs Question naire ( FABQ ) , the Tampa Scale for Kinesiophobia ( TSK ) , and the Pain Anxiety Symptoms Scale ( PASS ) . A total of 104 patients , presenting to a rehabilitation center or a comprehensive pain clinic with chronic low back pain were studied in three independent studies aim ed at ( 1 ) replicating that pain-related fear is more disabling than pain itself ( 2 ) investigating the association between pain-related fear and poor behavioral performance and ( 3 ) investigating whether pain-related fear measures are better predictors of disability and behavioral performance than measures of general negative affect or general negative pain beliefs ( e.g. pain catastrophizing ) . All three studies showed similar results . Highest correlations were found among the pain-related fear measures and measures of self-reported disability and behavioral performance . Even when controlling for sociodemographics , multiple regression analyses revealed that the subscales of the FABQ and the TSK were superior in predicting self-reported disability and poor behavioral performance . The PASS appeared more strongly associated with pain catastrophizing and negative affect , and was less predictive of pain disability and behavioral performance . Implication s for chronic back pain assessment , prevention and treatment are discussed Objective : To compare the effectiveness of an isokinetic exercise programme and a st and ard exercise programme in patients with chronic low back pain in terms of pain , mobility , disability , psychological status and muscle strength . Design : A r and omized controlled trial . Setting : An outpatient rehabilitation clinic . Subjects : A total of 40 patients with low back pain were included in the study . Interventions : Patients with low back pain were r and omly allocated into group 1 ( n=20 , isokinetic exercises ) and group 2 ( n=20 , st and ard exercise ) . Main measures : Outcome measures included a visual analogue scale ( VAS ) for pain , fingertip-to-floor test for spinal mobility , Modified Oswestry Low Back Disability Question naire ( MOLBDQ ) , Beck Depression Inventory and isokinetic muscle testing . Results : The isokinetic and st and ard exercise groups demonstrated significant improvement in the VAS , fingertip-to-floor test , MOLBDQ , Beck Depression Inventory scores , and muscle strength compared with the baseline that persisted until the end of the first month ( P<0.05 ) . Comparison of both exercise groups in terms of these parameters obtained at the end of the treatment and at the first month after treatment showed no significant difference ( P>0.05 ) . Conclusion : Isokinetic and st and ard exercise programmes have an equal effect in the treatment of low back pain , with no statistically significant difference found between the two programmes . The st and ard exercise programme was easily performed and had a low cost , making it the preferred option for exercise |
13,505 | 19,160,233 | Provision of physical rehabilitation interventions to long-term care residents is worthwhile and safe , reducing disability with few adverse events .
Most trials reported improvement in physical condition .
However , there is insufficient evidence to make recommendations about the best intervention , improvement sustainability and cost-effectiveness | BACKGROUND Examination of demographic trends indicates that the worldwide population is progressively ageing .
It is expected that such longevity will be associated with an increase in morbidity and dem and for long-term residential care .
This review examines whether there is evidence that physical rehabilitation benefits older people in long-term care .
OBJECTIVES To evaluate physical rehabilitation interventions directed at improving physical function among older people in long-term care . | Background Fatigue or lack of interest can reduce the feasibility of intensive physical exercise in nursing home residents . Low-volume exercise interventions with similar training effects might be an alternative . The aim of this r and omised controlled trial was to investigate the feasibility of Whole Body Vibration ( WBV ) in institutionalised elderly , and its impact on functional capacity and muscle performance . Methods Twenty-four nursing home residents ( 15 female , 9 male ; mean age 77.5 ± 11.0 years ) were r and omised ( stratification for age , gender and ADL-category ) to 6 weeks static WBV exercise ( WBV+ , N = 13 ) or control ( only static exercise ; N = 11 ) . Outcome measures were exercise compliance , timed up- and -go , Tinetti-test , back scratch , chair sit- and -reach , h and grip strength and linear isokinetic leg extension . Results At baseline , WBV+ and control groups were similar for all outcome variables . Twenty-one participants completed the program and attended respectively 96 % and 86 % of the exercise sessions for the WBV+ and control groups . Training-induced changes in timed up- and -go and Tinetti-test were better for WBV+ compared to control ( p = 0.029 for timed up- and -go , p = 0.001 and p = 0.002 for Tinetti body balance and total score respectively ) . In an alternative analysis ( Worst Rank Score & Last Observation Carried Forward ) the differences in change remained significant on the Tinetti body balance and total score . No other significant differences in change between both groups were observed . Conclusion In nursing home residents with limited functional dependency , six weeks static WBV exercise is feasible , and is beneficial for balance and mobility . The supplementary benefit of WBV on muscle performance compared to classic exercise remains to be explored further OBJECTIVE To use two different exercise programs over a 2-year period to reduce falls and their sequelae among residents of two long-term care facilities . DESIGN R and omized , controlled trial . SETTING The study took place at two long-term care facilities with services ranging from independent living to skilled nursing . PARTICIPANTS One hundred and ten participants whose average age was 84 and who were capable of ambulating with or without assistive devices and could follow simple directions . INTERVENTION Participants were r and omized to one of two exercise groups ( resistance/endurance plus basic enhanced programming or tai chi plus basic enhanced programming ) or to a control group ( basic enhanced programming only ) . Exercise classes were held three times per week throughout the study . MEASUREMENTS Participants were evaluated for cognitive and physical functioning at baseline and 6 , 12 , and 24 months . Falls were determined from incident reports filed by the nursing staffs at the facilities . RESULTS Time to first fall , time to death , number of days hospitalized , and incidence of falls did not differ among the treatment and control groups ( P>.05 ) . Among all participants , those who fell had significantly lower baseline Folstein Mini-Mental State Examination and instrumental activities of daily living scores and experienced significantly greater declines in these measures over the 2-year program . CONCLUSION There were no significant differences in falls among the two exercise groups and the control group . Lack of treatment differences and low adherence rates suggest that residents of long-term care facilities may require individualized exercise interventions that can be adapted to their changing needs This paper describes a quasi-experimental study of a musical exercise intervention to improve the physical , cognitive , behavioral status and life satisfaction of older residents in a long-term care facility in the United Kingdom . Twenty long-term care residents from three different units ( n=60 ) were recruited and assigned to one of three groups : a control ( C ) group ( no intervention ) , an occupational therapy ( OT ) group ( comparison group ) and a music exercise group ( intervention group ) . Assessment s of physical and cognitive status were made pre-intervention and repeated at the end of the 10-week exercise program and again 10 weeks after the completion of the program . The results show that both OT and exercise participation is associated with improvement in physical and cognitive function . However , the exercise group showed significant improvement in more areas than the OT group . The functional benefits from OT and exercise were not sustainable after these activities ceased and showed significant decline 10 weeks after the end of the programs OBJECTIVES To establish the effectiveness of a fall-prevention program in reducing falls and injurious falls in older residential care residents . DESIGN Cluster , r and omized , controlled trial . SETTING Fourteen r and omly selected residential care homes in Auckl and , New Zeal and . PARTICIPANTS All older residents ( n=628 , 95 % participation rate ) . INTERVENTION Residential care staff , using existing re sources , implemented systematic individualized fall-risk management for all residents using a fall-risk assessment tool , high-risk logo , and strategies to address identified risks . MEASUREMENTS Number of residents sustaining a fall , falls , and injurious-falls incidence rates . RESULTS During 12 months of follow-up , 103 ( 43 % ) residents in the control group and 173 ( 56 % ) residents in the intervention group fell ( P<.018 ) . There was a significantly higher incidence rate of falls in intervention homes than in control homes ( incident rate ratio=1.34 , 95 % confidence interval=1.06 - 1.72 ) during the intervention period after adjusting for dependency level ( type of home ) , baseline fall rate , and clustering . There was no difference in the injurious fall incidence rate or incidence of serious injuries . CONCLUSION This fall-prevention intervention did not reduce falls or injury from falls . Low-intensity intervention may be worse than usual care OBJECTIVE to determine the effect of risk factor modification and balance exercise on falls rates in residential care homes . DESIGN cluster r and omised controlled trial . PARTICIPANTS 196 residents ( aged 60 years or over ) in 20 residential care homes were enrolled ( 38 % response rate ) . Homes were r and omly allocated to intervention and control arms . A total of 102 residents were consigned to the intervention arm and 94 to the control arm . INTERVENTION a multifactorial falls prevention programme including 3 months gait and balance training , medication review , podiatry and optometry . MAIN OUTCOME MEASURES number of falls/recurrent falls per person , number of medications per person , and change in Tinetti gait and balance measure . RESULTS in the intervention group there was a mean of 2.2 falls per resident per year compared with 4.0 in the control group ; this failed to reach statistical significance ( P = 0.2 ) once the intra-cluster correlation ( ICC , 0.10 ) had been accounted for . Several risk factors were reduced in the intervention arm . CONCLUSIONS falls risk factor reduction is possible in residents of care homes . A modest reduction in falls rates was demonstrated but this failed to reach statistical significance Many studies have documented the effectiveness of verbally elicited imagery in the enhancement of motor skills in young , nondisabled population s. The present study examined the effects of verbally elicited imagery in the encouragement of two exercises ( i.e. , reaching up to pick apples and reaching down to pick up coins ) in elderly women . The subjects were 27 women between 62 and 96 years of age who were selected from a nursing home , a residential retirement home , and a foster care home . All of the subjects received imagery as well as control conditions , but in a counterbalanced fashion . The Wilcoxon matched-pairs signed rank tests indicated that the imagery condition elicited significantly more repetitions of the reaching-up exercise than did the control condition ( z = 2.25 , p [ one-tailed ] = .012 ) . The results in the reaching-down exercise were generally in the same direction but difficult to interpret statistically . The results are discussed in terms of other recent research investigating ways to add purpose to therapeutic exercise through occupation . Clinicians are urged to explore the advantages and disadvantages of imagery-based occupations in treatment The aims of this r and omised controlled trial were to determine if a high-intensity functional exercise program improves balance , gait ability , and lower-limb strength in older persons dependent in activities of daily living and if an intake of protein-enriched energy supplement immediately after the exercises increases the effects of the training . One hundred and ninety-one older persons dependent in activities of daily living , living in residential care facilities , and with a Mini-Mental State Examination ( MMSE ) score of ? 10 participated . They were r and omised to a high-intensity functional exercise program or a control activity , which included 29 sessions over 3 months , as well as to protein-enriched energy supplement or placebo . Berg Balance Scale , self-paced and maximum gait speed , and one-repetition maximum in lower-limb strength were followed-up at three and six months and analysed by 2 x 2 factorial ANCOVA , using the intention-to-treat principle . At three months , the exercise group had improved significantly in self-paced gait speed compared with the control group ( mean difference 0.04 m/s , p = 0.02 ) . At six months , there were significant improvements favouring the exercise group for Berg Balance Scale ( 1.9 points , p = 0.05 ) , self-paced gait speed ( 0.05 m/s , p = 0.009 ) , and lower-limb strength ( 10.8 kg , p = 0.03 ) . No interaction effects were seen between the exercise and nutrition interventions . In conclusion , a high-intensity functional exercise program has positive long-term effects in balance , gait ability , and lower-limb strength for older persons dependent in activities of daily living . An intake of protein-enriched energy supplement immediately after the exercises does not appear to increase the effects of the training OBJECTIVES To evaluate the effectiveness of a multifaceted , nonpharmaceutical intervention on incidence of falls and fallers . DESIGN Prospect i ve , cluster-r and omized , controlled 12-month trial . SETTING Six community nursing homes in Germany . PARTICIPANTS Long-stay residents ( n = 981 ) aged 60 and older ; mean age 85 ; 79 % female . INTERVENTIONS Staff and resident education on fall prevention , advice on environmental adaptations , progressive balance and resistance training , and hip protectors . MEASUREMENTS Falls , fallers , and fractures . RESULTS The incidence density rate of falls per 1,000 resident years ( RY ) was 2,558 for the control group ( CG ) and 1,399 for the intervention group ( IG ) ( relative risk ( RR ) = 0.55 , 95 % confidence interval ( CI ) = 0.41 - 0.73 ) . Two hundred forty-seven ( 52.3 % ) fallers were detected in the CG and 188 ( 36.9 % ) in the IG ( RR = 0.75 , 95 % CI = 0.57 - 0.98 ) . The incidence density rate of frequent fallers ( > 2/year ) was 115 ( 24.4 % ) for the CG and 66 ( 13.0 % ) for the IG ( RR = 0.56 , 95 % CI = 0.35 - 0.89 ) . The incidence density rate of hip fractures per 1,000 RY was 39 for the CG and 43 for the IG ( RR = 1.11 , 95 % CI = 0.49 - 2.51 ) . Other fractures were diagnosed with an incidence density rate of 52 per 1,000 RY for CG and 41 per 1,000 RY for IG ( RR = 0.78 , 95 % CI = 0.57 - 1.07 ) . CONCLUSION The incidence density rate of falls and fallers differed considerably between the control and intervention groups . The study was underpowered to demonstrate a significant difference of hip or nonhip fractures . Because of a low fracture rate in both groups , the investigation of fracture rates would have required a larger sample size to detect an effect of the intervention Abstract A r and omised controlled trial was undertaken to measure effects of exercise on : 1 . Progression of cognitive symptoms related to dementia using the Clock-Drawing Test ( Shulman et al. 1993 ) ; and 2 . Disability using the Revised Elderly Persons Disabilities Scale ( REPDS ; Fleming and Bowles 1993 ) . Data was analysed from 75 nursing home residents with dementia who were r and omly assigned to one experimental group and two control groups . Group 1 ( control ) received no intervention . Group 2 ( control ) received a social visit equivalent in duration and frequency as those undertaking the exercise program in the experimental group , Group 3 . A specifically design ed , frail aged appropriate , twelve-week exercise program was undertaken by the those in the experimental group three times per week . Each session lasted for 30 minutes . Findings from the : 1 . Clock-drawing test showed that exercise may slow the rate of progression of the cognitive symptoms related to dementia ; and 2 . REPDS showed that exercise slowed and reversed disability in some of the activities of daily living One of the effects of Alzheimer 's disease is a diminution in the ability to communicate . A r and omized , non-blinded two-group experimental study was undertaken to determine if planned walking has the capacity to improve the communication performance of patients with moderate to severe Alzheimer 's disease . Thirty subjects meeting NINCDS-ADRDA diagnostic criteria for probable Alzheimer 's disease , selected from two nursing homes , participated in the study . Intervention and comparison groups were each made up of subjects from both nursing homes . Subjects in one group were walked individually for 30 minutes three times a week for 10 weeks . Subjects in the comparison group were engaged in conversation for the same amount of time for 10 weeks . A multivariate analysis of variance ( MANOVA ) was performed on the communication data . Analysis of the data at post-testing indicated that communication performance improved significantly in the planned walking group over the conversation-only group ( f = 4.29 ; df = 2.28 ; P = 0.024 ) . The results suggest that a planned walking program has the capacity to improve the communication performance of patients with Alzheimer 's disease Objective : To compare the effectiveness of unsupervised home and supervised group exercise on parameters related to risk of falling among older adults . Design : Prospect i ve , single-blind , r and omized and controlled trial . Setting : Nursing home . Subjects : The subjects were selected from 535 independent individuals who resided in a nursing home . Forty-two older adults , aged > 65 years , with risk of falling were recruited , and 32 of them completed the study . Intervention : The 42 subjects were divided into two groups ( unsupervised home exercise and supervised exercise group ) r and omly . Exercise sessions were performed three times a week for a period of eight weeks . Main measures : Measurements were taken at baseline and after the completion of the exercise programme . The fear of falling was evaluated using a visual analogue scale , quadriceps muscle strength was measured with a dynamometer , flexibility was assessed with the sit and reach test , functional mobility was determined using the Timed Up and Go Test , balance was evaluated using one-leg and t and em st and ing , and Berg Balance Scale and proprioception was assessed with knee position sense . Results : Thirty-two subjects ( unsupervised home exercise n = 15 , supervised group exercise n = 17 ) completed the exercise programme and all of the measurements . The unsupervised home exercise group showed significant improvement in balance , functional mobility and flexibility ( P > 0.05 ) . In addition to balance , functional mobility and flexibility , the supervised exercise group also showed significant improvements in both strength and proprioception ( P > 0.05 ) . Conclusions : Supervised group exercise is more effective at reducing the risk factors related to falling among older adults living in a nursing home than is unsupervised home exercise OBJECTIVES To test the hypothesis that physical exercise induces an antiinflammatory response that is associated with reduced chronic activation of the tumor necrosis factor (TNF)-alpha system in frail elders and that the increase in muscle strength after resistance training is limited by systemic low- grade inflammation . DESIGN A 12-week controlled resistance-training study . SETTING Nursing homes in Copenhagen , Denmark . PARTICIPANTS Twenty-one frail nursing home residents aged 86 to 95 completed the study . INTERVENTION Ten participants were r and omized to a program of resistance training of knee extensors and flexors three times a week for 12 weeks ; the remaining 11 participants served as a control group who joined social activities supervised by an occupation therapist . MEASUREMENTS Muscle strength , plasma levels of TNF-alpha , soluble TNF receptor (sTNFR)-1 , and interleukin (IL)-6 were measured before and at the end of the intervention period . RESULTS The training program improved muscle strength but did not affect plasma levels of TNF-alpha and sTNFR-I or IL-6 . However , plasma levels of sTNFR-I at baseline were inversely correlated with the increase in muscle strength . CONCLUSION Low- grade activation of the TNF system could limit the increase in muscle strength after resistance training in the oldest old . Furthermore , data suggest that the antiinflammatory response induced by 12 weeks of resistance training is not sufficient to reduce chronic activation of the TNF system , but the small sample size limited this interpretation OBJECTIVES To determine the effects of moderate intensity group-exercise programs on falls , functional performance , and disability in older adults ; and to investigate the influence of frailty on these effects . DESIGN A 20-week , multicenter r and omized controlled trial , with 52-week follow-up . SETTING Fifteen homes for the elderly . PARTICIPANTS Two hundred seventy-eight men and women ( mean age + /- st and ard deviation , 85+/-6y ) . INTERVENTIONS Two exercise programs were r and omly distributed across 15 homes . The first program , functional walking ( FW ) , consisted of exercises related to daily mobility activities . In the second program , in balance ( IB ) , exercises were inspired by the principles of Tai Chi . Within each home participants were r and omly assigned to an intervention or a control group . Participants in the control groups were asked not to change their usual pattern of activities . The intervention groups followed a 20-week exercise program with 1 meeting a week during the first 4 weeks and 2 meetings a week during the remaining weeks . MAIN OUTCOME MEASURES Falls , Performance Oriented Mobility Assessment ( POMA ) , physical performance score , and the Groningen Activity Restriction Scale ( GARS ) ( measuring self-reported disability ) . RESULTS Fall incidence rate was higher in the FW group ( 3.3 falls/y ) compared with the IB ( 2.4 falls/y ) and control ( 2.5 falls/y ) groups , but this difference was not statistically significant . The risk of becoming a faller in the exercise groups increased significantly in the subgroup of participants who were classified as being frail ( hazard ratio [ HR ] = 2.95 ; 95 % confidence interval [ CI ] , 1.64 - 5.32 ) . For participants who were classified as being pre-frail , the risk of becoming a faller decreased ; this effect became significant after 11 weeks of training ( HR = .39 ; 95 % CI , .18-.88 ) . Participants in both exercise groups showed a small , but significant improvement in their POMA and physical performance scores . In the FW group , this held true for the GARS score as well . Post hoc analyses revealed that only the pre-frail participants improved their POMA and physical performance scores . CONCLUSIONS Fall-preventive moderate intensity group-exercise programs have positive effects on falling and physical performance in pre-frail , but not in frail elderly OBJECTIVE The purpose of this study was to determine if 1.0 Full-time Equivalent ( FTE ) physical therapy ( PT ) and 1.0 FTE occupational therapy ( OT ) per 50 beds result ed in differences in functional status for nursing home residents when compared to 1.0 FTE PT and 1.0 FTE OT per 200 beds . DESIGN R and omized control program evaluation , cost analysis . SETTING Nursing home in the province of Alberta , Canada . PATIENTS 115 residents assigned to 1 PT and 1 OT per 50 beds ( enhanced group ) versus 1 PT and 1 OT per 200 beds ( control group ) using stratified r and om allocation by severity of condition . INTERVENTIONS Both groups received ongoing treatment , follow-up , and restorative interventions , but enhanced group received more hours of service . OUTCOME MEASURES Functional Independence Measure ( FIM ) , Functional Assessment Measures ( FAM ) , and Clinical Outcome Variables Scale ( COVS ) recorded at 6-month intervals over a 2-year period . RESULTS Mean score differences favored the enhanced group for the tests over the 2 years . Significance was observed on FIM Total at 6 and 12 months , FIM Self Care at 6 months , FIM Communication at 24 months , and FIM Psychosocial at 6 , 12 , 18 , and 24 months ; FAM Total at 6 , 12 , 18 , and 24 months , FAM Self Care at 6 months , FAM Mobility at 12 months , FAM Communication at 6 and 24 months , FAM Psychosocial at 6 , 12 , 18 , and 24 months , and FAM Cognition at 6 and 12 months ; and COVS at 6 , 12 , 18 , and 24 months . A cost analysis demonstrated that PT/OT offered at the 1:50 ratio would result in a cost savings in terms of nursing staff dollars for 30 long-term-care beds of $ 16,973 over the 2 years of the study compared to the 1:200 ratio . This equates to an annual cost savings of $ 283 per bed . CONCLUSIONS Increasing the amount of PT/OT can have a positive effect on the functional status and cost of care of long-term care residents OBJECTIVES To determine the effect of a 12-week intervention to improve the ability of disabled older adults to rise from a bed and from a chair . DESIGN Subjects were r and omly allocated to either a 12-week task-specific resistance-training intervention ( training in bed- and chair-rise subtasks , such as sliding forward to the edge of a chair with the addition of weights ) or a control flexibility intervention . SETTING Seven congregate housing facilities . PARTICIPANTS Congregate housing residents age 65 and older ( n = 161 , mean age 82 ) who reported requiring assistance ( such as from a person , equipment , or device ) in performing at least one of the following mobility-related activities of daily living : transferring , walking , bathing , and toileting . MEASUREMENTS At baseline , 6 weeks , and 12 weeks , subjects performed a series of bed- and chair-rise tasks where the rise task dem and varied according to height of the head of the bed , chair seat height , and use of h and s. Outcomes were able or unable to rise and , if able , the time taken to rise . Logistic regression for repeated measures was used to test for differences between tasks in the ability to rise . Following log transformation of rise time , a linear effects model was used to compare rise time between tasks . RESULTS Regarding the maximum total number of bed- and chair-rise tasks that could be successfully completed , a significant training effect was seen at 12 weeks ( P = .03 ) ; the training effect decreased as the total number of tasks increased . No statistically significant training effects were noted for rise ability according to individual tasks . Bed- and chair-rise time showed a significant training effect for each rise task , with analytic models suggesting a range of approximately 11 % to 20 % rise-time ( up to 1.5 seconds ) improvement in the training group over controls . Training effects were also noted in musculoskeletal capacities , particularly in trunk range of motion , strength , and balance . CONCLUSIONS Task-specific resistance training increased the overall ability and decreased the rise time required to perform a series of bed- and chair-rise tasks . The actual rise-time improvement was clinical ly small but may be useful over the long term . Future studies might consider adapting this exercise program and the focus on trunk function to a frailer cohort , such as in rehabilitation setting s. In these setting s , the less challenging rise tasks ( such as rising from an elevated chair ) and the ability to perform intermediate tasks ( such as hip bridging ) may become important intermediate rehabilitation goals Seven recent experimental and quasi-experimental studies have compared the exercise of subjects instructed to pursue some added goal ( often termed purpose ful activity ) with the exercise of subjects instructed to exercise without the suggestion of an added goal ( often termed non purpose ful activity ) . This article suggests a new terminology for this type of independent variable and describes an experiment within this developing tradition . An occupational form design ed , through material s and instructions , to elicit a rotary arm exercise with the added purpose of stirring cookie dough was compared with an occupational form design ed to elicit the rotary arm exercise with no added purpose . The subjects were 30 elderly female nursing home residents r and omly assigned to the occupational forms . Results indicated that the added- purpose , occupationally embedded exercise condition elicited significantly more exercise repetitions than did the rote exercise condition ( one-tailed p = .012 ) . Exercise duration and exercise stoppages were also recorded . This study provides additional support for the traditional occupational therapy idea of embedding exercise within occupation . Suggestions are made for future research involving the experimental analysis of therapeutic occupation This study examined the effects of indoor gardening on socialization , activities of daily living ( ADLs ) , and perceptions of loneliness in elderly nursing home residents . A total of 66 residents from two nursing homes participated in this two-phase study . In phase one , experimental group 1 participated once a week for 5 weeks in gardening activities while a control group received a 20-minute visit . While no significant differences were found between groups in socialization or perceptions of loneliness , there were significant pretest-posttest differences within groups on loneliness and guidance , reassurance of worth , social integration , and reliable alliance . The results also demonstrated gardening interventions had a significant effect on three ADLs ( transfer , eating , and toileting ) . Phase two examined differences in the effects of a 5-week versus a 2-week intervention program . Although no significant within-group differences were noted in socialization , loneliness , or ADLs , the 5-week program was more effective in increasing socialization and physical functioning OBJECTIVES To determine the effects of a 12-week walking program on walk endurance capacity , physical activity level , mobility , and quality of life in ambulatory nursing home residents who had been identified as having low physical activity levels and low walk endurance capacities . To determine the effects of 12 versus 22 weeks of walk training on walk endurance capacity , physical activity level , mobility , and quality of life in ambulatory nursing home residents . DESIGN Experiment 1 : Residents of one nursing home campus were assigned to the walking program , and residents of a second campus were assigned to the social visit control group . Outcome measures were taken before and after 12 weeks . Experiment 2 : Pretest/posttest with outcome measures taken before and , again , after 12 and 22 weeks of walking . SETTING Two campuses of the Jewish Homes for the Aging in the Los Angeles area . PARTICIPANTS Experiment 1 : Nineteen of 22 residents in the walking group completed the walking program , and 12 of 15 residents in the control group completed the study . Experiment 2 : Thirty of 41 residents ( from the two nursing homes ) completed the 22-week walking program . INTERVENTION Experiment 1 : The walking program involved each resident walking with research staff at his/her self-selected walking pace , 5 days per week for 12 weeks , for a maximum of 30 minutes per day ; while the control group had weekly individual social visits , which lasted 30 minutes , from a research assistant . Experiment 2 : All residents , those in both the walking and the control group , were offered the opportunity to complete 22 weeks of walking . MAIN OUTCOME MEASURES Maximal walk endurance capacity , the resident 's maximum walk time performed in a single day of walking ( distance and speed also were measured ) ; physical activity level based on time- sample d observations and physical activity monitors ; mobility as measured with the Timed-Up- and -Go test , left h and grip strength , and Tinetti 's Mobility Assessment ; and quality of life as assessed with the Geriatric Depression Scale ( a bodily pain scale ) and the Dartmouth Primary Care Cooperative Information Project ( COOP ) physical work chart . RESULTS Experiment 1 : The walking group significantly improved their maximal walk endurance time by 77 % and distance by 92 % , with no significant change in walk speed ; however , the control group showed no significant changes in these variables . There were no significant group by time interactions on measures of physical activity , mobility , and quality of life . Experiment 2 : No further significant changes were found from 12 to 22 weeks in walk endurance capacity , physical activity , mobility , or quality of life . CONCLUSION Twelve weeks of daily walking at a self-selected walking pace by ambulatory nursing home residents produced significant improvements in walk endurance capacity . No other significant changes were noted in physical activity level , mobility , or quality of life in either group after the intervention . Also , there were no side effects , such as increases in falls or cardiovascular complications , due to the walking intervention . Lengthening the walking program to 22 weeks produced no further significant changes in any outcome measures Background and Purpose — A pilot evaluation of an occupational therapy intervention to improve self-care independence for residents with stroke-related disability living in care homes was the basis of this study . Methods — A cluster r and omized controlled trial with care home as the unit of r and omization was undertaken in Oxfordshire , UK . Twelve homes ( 118 residents ) were r and omly allocated to either intervention ( 6 homes , 63 residents ) or control ( 6 homes , 55 residents ) . Occupational therapy was provided to individuals but included carer education . The control group received usual care . Assessment s were made at baseline , postintervention ( 3 months ) and at 6-months to estimate change using the Barthel Activity of Daily Living Index ( BI ) scores , “ poor global outcome ” , ( defined as deterioration in BI score , or death ) and the Rivermead Mobility Index . Results — At 3 months BI score in survivors had increased by 0.6 ( SD 3.9 ) in the intervention group and decreased by 0.9 ( 2.2 ) in the control group ; a difference of 1.5 ( 95 % CI allowing for cluster design , −0.5 to 3.5 ) . At 6 months the difference was 1.9 ( −0.7 to 4.4 ) . Global poor outcome was less common in the intervention group . At 3 months , 20/63 ( 32 % ) were worse/dead in the intervention group compared with 31/55 ( 56 % ) in the control group , difference −25 % ( −51 % to 1 % ) . At 6 months the difference was similar , −26 % ( −48 % to −3 % ) . Between-group changes in Rivermead Mobility Index scores were not significantly different . Conclusion — Residents who received an occupational therapy intervention were less likely to deteriorate in their ability to perform activities of daily living Objective Although exercise therapy intervention for frail elderly people was not of great interest in the past , it has recently drawn attention as a method to prevent and improve conditions requiring care since the enforcement of the Long-Term Care Insurance Law and the revision of the long-term care insurance system . This r and omized controlled trial was performed to evaluate the effects of exercise therapy using the Takizawa Program . Methods In this r and omized controlled trial , we evaluated the effects of exercise therapy on the frail elderly , including those who need a high level of care , in terms of two factors : the range of motion and the functional independence measure . The subjects were 145 females admitted to special nursing homes for the elderly . They were stratified according to their care levels and r and omly assigned to either the exercise therapy intervention group or the control group . Results The range of motion values in the flexions of both shoulders , the right knee extension , and the dorsal flexions of both ankles significantly increased only in the exercise therapy intervention group . The functional independence measure score did not improve in the exercise therapy intervention group . Conclusion Exercise therapy should be used for the frail elderly requiring a high level of care Objective : To evaluate the specific effects of balance and gait exercises among frail elderly individuals . Design : A r and omized three-group parallel controlled study . Setting : Geriatric health services facility in Japan . Subjects : Thirty-four frail elderly subjects attending the care facility were r and omized into a control group , an exercise group with emphasis on balance or an exercise group with emphasis on gait re-education . Interventions : The two exercise groups received balance or gait exercise for 40 minutes , 2–3 times weekly , for 12 weeks . Main outcome measures : One Leg St and ing Test , Functional Reach Test , Manual Perturbation Test , Functional Balance Scale , Performance-Oriented Mobility Assessment , Timed ‘ Up and Go ’ Test and Stair Climbing/Descending Test . These assessment s were performed before and after 12-week intervention . Results : Comparison of the performance before and after intervention demonstrated significant improvement in One Leg St and ing Test , Functional Reach Test and Functional Balance Scale in the balance exercise group , and Functional Balance Scale , Timed ‘ Up and Go ’ Test and Stair Descending Test showed improvement in the gait exercise group . All test items showed no significant differences in the control groups . Among the three groups , the balance exercise group showed more significant improvement in Functional Balance Scale , and the gait exercise group showed more significant improvement in Performance-Oriented Mobility Assessment than the control group . The balance exercise group showed greater improvement in performance in Functional Reach Test than the gait exercise group . Conclusions : Balance exercises led to improvements in static balance function , and gait exercises result ed in improvements to dynamic balance and gait functions in the very frail elderly BACKGROUND Past studies suggest multidisciplinary interventions that include physical therapy ( PT ) can improve function of nursing home residents . This trial specifically evaluates effects of PT for frail long-stay nursing home residents . DESIGN R and omized , controlled trial . SETTING One academic nursing home and eight community nursing homes . PATIENTS A total of 194 elderly nursing home residents dependent in at least two activities of daily living residing in the nursing home for at least 3 months . INTERVENTIONS Patients were r and omized to individually tailored one-on-one PT sessions or friendly visits ( FVs ) three times a week for 4 months . Physical therapy included range-of-motion , strength , balance , transfer , and mobility exercises . MAIN OUTCOME MEASURES Performance-based physical function assessed by the Physical Disability Index ; self-perceived health status assessed with the Sickness Impact Profile ; observer-reported activities of daily living ; and falls . RESULTS Eighty-nine percent and 92 % of PT and FV sessions , respectively , were attended ; 5 % and 9 % of subjects dropped out in the PT group and FV group , respectively . Compared with the FV group , the PT group experienced no significant improvements in overall Physical Disability Index , Sickness Impact Profile , or activities of daily living scores . A 15.5 % improvement in the mobility subscale of the Physical Disability Index was seen ( 95 % confidence interval [ CI ] , 6.4 % to 24.7 % ) ; no benefits in range-of-motion , strength , or balance subscales were found . Compared with the FV group , the PT group used assistive devices for bed mobility tasks less often ( P = .06 ) and were less likely to use assistive devices and wheelchairs for locomotion ( P < .005 ) . There were 79 falls in the PT group vs 60 falls in the FV group ( P = .11 ) . Charge for the 4-month PT program was $ 1220 per subject ( 95 % CI , $ 412 to $ 1832 ) . CONCLUSION This st and ardized physical therapy program provided modest mobility benefits for very frail long-stay nursing home residents with physical disability due to multiple comorbid conditions This study was design ed to compare the results of a traditional method of stretching knee flexion contractures by high-load brief stretch ( HLBS ) with the results of an experimental method of prolonged knee extension by skin traction , low-load prolonged stretch ( LLPS ) . End range of passive knee extension was measured by st and ard goniometry . Subjects were 11 nonambulatory residents of a nursing home who had demonstrated gradually progressive bilateral knee contractures . Each subject served as his or her own control with one lower limb receiving LLPS and the other limb receiving HLBS and passive range of motion ( PROM ) . Sequential medical trials were used as the clinical research design . Whether comparing the LLPS limb PROM measurements pretreatment and posttreatment ( p less than or equal to .05 ) or the HLBS to the LLPS limb PROM recordings posttreatment ( p less than or equal to .05 ) , the results demonstrated a preference for LLPS in the treatment of knee contractures in the immobile nursing home resident OBJECTIVE To investigate the effects of whole body vibration in the elderly . DESIGN R and omized controlled trial . SETTING Nursing home . PARTICIPANTS Forty-two elderly volunteers . INTERVENTIONS Six-week vibration intervention plus physical therapy ( PT ) ( n=22 ) or PT alone ( n=20 ) . MAIN OUTCOME MEASURES We assessed gait and body balance using the Tinetti test ( maximum scores of 12 for gait , 16 for body balance , 28 for global score ) , motor capacity using the Timed Up & Go ( TUG ) test , and health-related quality of life ( HRQOL ) using the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) . RESULTS After 6 weeks , the vibration intervention group improved by a mean + /- st and ard deviation of 2.4+/-2.3 points on the gait score compared with no score change in the control group ( P < .001 ) . The intervention group improved by 3.5+/-2.1 points on the body balance score compared with a decrease of 0.3+/-1.2 points in the control group ( P < .001 ) . TUG test time decreased by 11.0+/-8.6 seconds in the treated group compared with an increase of 2.6+/-8.8 seconds in the control group ( P < .001 ) . The intervention group had significantly greater improvements from baseline on 8 of 9 items on the SF-36 compared with the control group . CONCLUSIONS Controlled whole body vibration can improve elements of fall risk and HRQOL in elderly patients Residents and staff of a nursing home in a metropolitan area were r and omly assigned to three conditions to : ( a ) test whether staff 's use of operant behavioural management strategies ( Condition 1 ) would cause a greater increase in residents ' self-care behaviour than staff 's use of mutual goal setting ( Condition 2 ) or routine nursing care ( Condition 3 ) , and ( b ) examine how useful group scores were , compared to individual scores , in determining change in individual residents ' behaviour due to treatment . In-service training was provided to staff in Conditions 1 and 2 but not in Condition 3 . Over a period of 22 weeks , nursing staff encouraged subjects to perform targeted self-care tasks independently . Data analysis indicated significantly greater change in self-care behaviours for subjects in Condition 1 than for subjects in Conditions 2 and 3 . However , visual inspection of data for each case revealed that individual scores were more useful than averages and differences between groups for determining the effectiveness of the clinical interventions Background and aims : Loss of balance is a major risk factor for falls in the elderly , and physical exercise may improve balance in both elderly and middle-aged people . We propose a clinical trial to test the efficacy of an exercise program based on dance in improving balance in adult and young old subjects . Methods : We carried out a mono-institutional , r and omized , controlled clinical trial . 40 subjects ( aged 58 to 68 yr ) were r and omly allocated in two separate groups : the exercise group ( n=20 ) followed a 3- month exercise program ; the control group ( n=20 ) did not engage in physical activities . Differences in balance between the end of the training period and the baseline were assessed using four different balance tests : Tinetti , Romberg , improved Romberg , Sit up and go . Results : Results showed a significant improvement in balance in the exercise group at the end of the exercise program , whereas the control group did not show any significant changes . The comparison between exercise and control group variations in balance test scores showed a highly significant difference . 17 out of 20 subjects in the exercise group reported great or moderate satisfaction with the dance activity . Conclusions : Results suggest that physical activity based on dance may improve balance and hence be a useful tool in reducing the risk of falling in the elderly . The exercise program also revealed interesting psychosocial benefits OBJECTIVES To test the effects of the Psychomotor Activation Programme ( PAP ) on the behaviour and cognition of demented elderly people . DESIGN R and omized controlled trial with an experimental group and a control group . Post-test after 6 months . SETTING Group care projects for demented elderly people living in 11 different homes for the elderly in The Netherl and s. PARTICIPANTS One hundred and thirty-four subjects entered the study ( 72 in the experimental group and 62 in the control group ) , 42 of whom dropped out ( 27 in the experimental group and 15 in the control group ) . MEASUREMENTS Individual behaviour and group behaviour were scored using two Dutch scales ( BIP and SIPO respectively ) developed and vali date d for use in psychogeriatric population s. Cognition was measured with the short and the long versions of the Cognitive Screening Test ( CST-14 and CST-20 ) . Disability was measured with the Barthel Index . Medicine use , falls , other accidents and life events were registered . RESULTS The PAP had a beneficial effect on cognition ( CST-14 , F = 2.63 , p < or = 0.05 , effect size 0.4 ) ( CST-20 , F = 3.77 , p < or = 0.05 , effect size 0.5 ) and increased positive group behaviour in participants with relatively mild cognitive problems ( SIPO , F = 4.46 p < or = 0.05 ) . CONCLUSIONS The PAP stabilizes cognitive performance and has some beneficial effects on behaviour . Positive findings were supported by a simultaneously conducted process evaluation Material s-based occupation , imagery-based occupation , and rote exercise have been examined individually by several research ers . The present study compares all three approaches with one another ( i.e. , kicking a balloon , imagining kicking a balloon , and a control rote exercise ) in nursing home residents . The dependent variable was the number of exercise repetitions . The subjects were 12 women and 3 men between 56 and 93 years of age residing in two nursing homes . All subjects experienced the three approaches but in different orders . One-way analysis of variance for related measures indicated a significant difference among conditions ( p = .004 ) . The Tukey procedure ( Stevens , 1986 ) determined that the material s-based occupation condition elicited significantly more repetitions than the other two conditions . The difference between the imagery-based occupation and rote exercise was not statistically significant . These findings support our profession 's historical emphasis on the use of physical material s to enhance performance OBJECTIVES The purpose of this study was to test whether an intervention combining increased daytime physical activity with improvement in the nighttime environment improves sleep and decreases agitation in nursing home residents . DESIGN A r and omized trial . SETTING One community nursing home in the Los Angeles , California area . PARTICIPANTS Twenty-nine incontinent residents ( mean age 88.3 years , 90 % female ) . INTERVENTION Subjects were r and omized to receive either ( 1 ) an intervention combining increased daytime physical activity ( 14 weeks in duration ) plus a nighttime program ( 5 nights in duration ) to decrease noise and sleep-disruptive nursing care practice s ( intervention group ) , or ( 2 ) the nighttime program alone ( control group ) . MEASUREMENTS Daytime physical activity monitors and structured physical function assessment s ; nighttime wrist activity monitors to estimate nighttime sleep ; and timed daytime behavioral observations of sleep versus wakefulness , either in or out of bed , and agitation . RESULTS Physical function measures did not change significantly ( MANOVA for repeated measures , group by time effect ) . Wrist actigraphy estimation of nighttime percent sleep ( time asleep over time monitored in bed at night ) increased in intervention subjects from 51.7 % at baseline to 62.5 % at follow-up compared with 67.0 % at baseline to 66.3 % at follow-up in controls ( MANOVA , group by time , F = 4.42 , P = .045 , df = 27 ) . At follow-up , intervention subjects averaged a 32 % decrease in the percent of daytime observations in bed compared with baseline , with essentially no change in controls ( MANOVA , group by time , F = 5.31 , P = .029 , df = 27 ) . Seven of 15 intervention subjects had a decrease in observed agitation at follow-up , compared with baseline , versus only 1 of 14 controls with a decrease in observed agitation . CONCLUSIONS This study provides preliminary evidence that an intervention combining increased physical activity with improvement in the nighttime nursing home environment improves sleep and decreases agitation in nursing home residents Regular exercise is widely advocated for the young and middle-aged , but less is heard about its relevance to elderly people . This study reports the findings of a controlled trial of seated exercise in residents of local authority homes for the elderly . Forty-nine residents aged 64 - 91 years volunteered for the 7-month project , and participated in either twice-weekly exercise or reminiscence sessions . Primary outcome measures were postural sway , flexibility of the spine and knees , h and -grip strength and functional capacity . The average ( range of ) attendance at the exercise sessions was 91 % ( 64 - 100 % ) , and at the reminiscence sessions was 86 % ( 46 - 100 % ) . By the end of the project , the change observed in the exercise group was significantly different from that of the reminiscence group in terms of grip strength ( p < 0.02 ) , spinal flexion ( p < 0.001 ) , chair-to-st and time ( p < 0.001 ) , activities of daily living ( p < 0.05 ) , and self-rating of depression ( p < 0.01 ) . Even very elderly residents of old peoples homes can benefit from participation in regular seated exercise and improve their functional capacity BACKGROUND AND PURPOSE Although contractures in patients in long-term care institutions are an important issue , there have been only a few studies that have evaluated interventions for contractures . The purpose of this study was to determine the effectiveness of a bed positioning program ( BPP ) for the treatment of patients with knee flexion contractures . SUBJECTS Sixteen patients with a high level of cognitive and functional impairment ( mean age=82 years , SD=6.48 , range=71 - 93 ) in a chronic care hospital participated in the study . METHODS The BPP consisted of stretching a patient 's knee into extension and then securing and maintaining the position for a period of 40 minutes , 4 times per week . Participants were r and omly assigned to 2 groups ( n=8 in each group ) . One group received a BPP for 8 weeks , followed by 8 weeks of no intervention . The other group received the intervention in the reverse order . Once a week , participants were assessed for range of knee extension , knee pain , and skin integrity . RESULTS Twelve participants completed the study . There was no improvement in participants ' range of knee extension during the intervention period . Overall , there was no difference in mean range of knee extension between the intervention period and the no-intervention period . CONCLUSION AND DISCUSSION The results of this study do not support the use of a BPP for treating patients with knee flexion contractures The purpose of this study was to investigate the effects of a walking/talking program on residents ' communication , ambulation , and level of function when there were two residents to one care provider ( 2:1 ) . A r and omized control trial design was used . Subjects were residents with Alzheimer disease in three geriatric long-term care facilities in Metropolitan Toronto . Residents who met the inclusion criteria were r and omly assigned to one of three groups : walk- and -talk group ( 30 min , 5 times per week for 16 weeks , walking/talking in pairs ) , talk-only group ( 30 min , 5 times per week for 16 weeks , talk only in pairs ) , or no intervention . The outcome measures were the Functional Assessment of Communication Skills for Adults , the 2-min walk test , and London Psychogeriatric Rating Scale . Residents who received the walk- and -talk intervention did not demonstrate statistically significant differences in the outcome variables measured posttest when compared with residents who received the talk-only intervention or no intervention , even after controlling for individual differences . Variability in the outcomes measured posttest is explained by differences in the residents ' level of cognitive impairment before the study rather than by study group membership . These findings are contradictory to those of previous studies Background and aims : Impaired mobility is one of the strongest predictors for falls in older people . We hypothesized that exercise as part of a fall prevention program would have positive effects , both short- and long-term , on gait , balance and strength in older people at high risk of falling and with varying levels of cognition , residing in residential care facilities . A secondary hypothesis was that these effects would be associated with a reduced risk of falling . Methods : 187 out of all residents living in 9 facilities , ≥65 years of age were at high risk of falling . The facilities were clusterr and omized to fall intervention or usual care . The intervention program comprised : education , environment , individually design ed exercise , drug review , post-fall assessment s , aids , and hip protectors . Data were adjusted for baseline performance and clustering . Results : At 11 weeks , positive intervention effects were found on independent ambulation ( FAC , p=0.026 ) , maximum gait speed ( p=0.002 ) , and step height ( ≥10 cm , p<0.001 ) , but not significantly on the Berg Balance Scale . At 9 months ( long-term outcome ) , 3 intervention and 15 control residents had lost the ability to walk ( p=0.001 ) . Independent ambulation and maximum gait speed were maintained in the intervention group but deteriorated in the control group ( p=0.001 ) . Residents with both higher and lower cognition benefited in most outcome measures . No association was found between improved mobility and reduced risk of falling . Conclusions : Exercise , as part of a fall prevention program , appears to preserve the ability to walk , maintain gait speed , ambulate independently , and improve step height . Benefits were found in residents with both lower and higher cognitive impairment , but were not found to be associated with a reduced risk of falling The purpose of this study was to determine whether a moderate to high intensity strengthening and aerobic exercise program can improve the strength , exercise capacity , gait and balance of deconditioned male nursing home residents . Ambulatory subjects who scored 30 or less on the modified Tinetti gait and balance assessment scale , who demonstrated less than 80 % of age-matched lower extremity strength on isokinetic muscle testing and who gave informed consent were enrolled . Subjects were r and omized to either an exercise ( n = 8) or a control ( n = 6 ) group . All participants underwent an exercise test to determine maximal oxygen uptake ( Vo2max ) and received quantitative gait and balance measurements . The subjects assigned to the exercise group then completed a 12-wk program of weight training for the lower extremities and stationary cycling . Both the exercise and control groups were then retested . Ten outcome variables were assessed : Tinetti mobility scores , Vo2max , isokinetic-tested lower extremity strength and endurance , stride length , gait velocity , stance time , gait duration , cadence and balance . The exercise group , after completion of the program , demonstrated significant improvements in Tinetti mobility scores ( P < 0.05 ) , combined right and left quadricep muscle strength ( P < 0.01 ) , right and left lower extremity muscular endurance ( P < 0.01 ) , left stride length and gait velocity ( P < 0.05 ) , although other outcome variables changed insignificantly . The control group revealed no changes of significance with the exception of improvement of the combined right and left hamstring muscle strength ( P < 0.05 ) . Nevertheless , for those outcome variables that had improved significantly in the exercise group , the changes amounted to only a 5 to 10 % increase over the baseline measurements . These findings showed that an appropriately design ed high intensity exercise program can result in significant although limited improvements for clinical mobility scores , strength , muscular endurance and certain gait parameters OBJECTIVES To investigate the effectiveness of an exercise program in improving ability to perform activities of daily living ( ADLs ) , physical performance , and nutritional status and decreasing behavioral disturbance and depression in patients with Alzheimer 's disease ( AD ) . DESIGN R and omized , controlled trial . SETTING Five nursing homes . PARTICIPANTS One hundred thirty-four ambulatory patients with mild to severe AD . INTERVENTION Collective exercise program ( 1 hour , twice weekly of walk , strength , balance , and flexibility training ) or routine medical care for 12 months . MEASUREMENTS ADLs were assessed using the Katz Index of ADLs . Physical performance was evaluated using 6-meter walking speed , the get-up- and -go test , and the one-leg-balance test . Behavioral disturbance , depression , and nutritional status were evaluated using the Neuropsychiatric Inventory , the Montgomery and Asberg Depression Rating Scale , and the Mini-Nutritional Assessment . For each outcome measure , the mean change from baseline to 12 months was calculated using intention-to-treat analysis . RESULTS ADL mean change from baseline score for exercise program patients showed a slower decline than in patients receiving routine medical care ( 12-month mean treatment differences : ADL=0.39 , P=.02 ) . A significant difference between the groups in favor of the exercise program was observed for 6-meter walking speed at 12 months . No effect was observed for behavioral disturbance , depression , or nutritional assessment scores . In the intervention group , adherence to the program sessions in exploratory analysis predicted change in ability to perform ADLs . No adverse effects of exercise occurred . CONCLUSION A simple exercise program , 1 hour twice a week , led to significantly slower decline in ADL score in patients with AD living in a nursing home than routine medical care BACKGROUND AND PURPOSE This prospect i ve clinical investigation examined the effects of a multidimensional exercise program on balance , mobility , and risk for falls in community-dwelling older adults with a history of falling . Factors used to predict adherence and a successful response to exercise were identified . SUBJECTS A total of 105 community-dwelling older adults ( > or = 65 years of age ) with a history of two or more falls in the previous 6 months ( no neurologic diagnosis ) participated . They were classified into ( 1 ) a control group of fallers ( n = 21 ) , ( 2 ) a fully adherent exercise group ( n = 52 ) , and ( 3 ) a partially adherent exercise group ( n = 32 ) . METHODS Following evaluation , each patient received an individualized exercise program addressing the impairments and functional disabilities identified during the assessment . The control group received no intervention . Changes in performance on five clinical tests of balance and mobility and fall risk were compared among groups . RESULTS Both exercise groups scored better than the control group on all measures of balance and mobility . Although both exercise groups showed a reduction in fall risk compared with the control group , the greatest reduction was found in the fully adherent exercise group . Factors associated with successful response to exercise included degree of adherence to exercise program and pretest score on the Tinetti Mobility Assessment . CONCLUSION AND DISCUSSION Exercise can improve balance and mobility function and reduce the likelihood for falls among community-dwelling older adults with a history of falling . The amount of exercise needed to achieve these results , however , could not be determined from this study OBJECTIVES To examine clinical outcomes and describe the staffing requirements of an incontinence and exercise intervention . DESIGN R and omized controlled trial with blinded assessment s of outcomes at three points over 8 months . SETTING Four nursing homes . PARTICIPANTS Two hundred fifty-six incontinent residents . INTERVENTION Research staff provided the intervention , which integrated incontinence care and exercise every 2 hours from 8:00 a.m. to 4:00 p.m. 5 days a week . MEASUREMENTS Average and maximum distance walked or wheeled , level of assistance required to st and , maximum pounds lifted by arms , fecal and urinary incontinence frequency , and time required to implement intervention . RESULTS Intervention residents maintained or improved performance whereas the control group 's performance declined on 14 of 15 outcome measures . Repeated measures analysis of variance group-by-time significance levels ranged from P < .0001 to.05 . The mean time required to implement the intervention each time care was provided was 20.7 + /- 7.2 minutes . We estimate that a work assignment of approximately five residents to one aide would be necessary to provide this intervention . CONCLUSIONS The incontinence care and exercise intervention result ed in significant improvement for most residents , and most who could be reliably interviewed expressed a preference for such care . Fundamental changes in the staffing of most nursing homes will be necessary to translate efficacious clinical interventions into everyday practice Health in older adults can best be measured in terms of functional status . Skeletal muscle strength has been reported to be a determinant of functional status in older individuals . Two major contributors to the decline in muscle function as a person ages are disuse and physical inactivity . Declining muscle function through a loss of muscular strength may decrease functional independence and mobility and increase the risk for falls and injuries , physical frailty , and disability . Older individuals lacking an appropriate amount of muscular strength may not be able to perform various activities of daily living , which are important indicators of independence Purpose : The present study investigated which additional cognitive and motor impairments were present in stroke patients with apraxia and which of these factors influenced the effects of treatment . Method : A group of 33 patients with apraxia were treated according to the guidelines of a therapy programme based on teaching patients strategies to compensate for the presence of apraxia . Patients were treated at occupational therapy departments in general hospitals , rehabilitation centres and nursing homes . The outcome of the strategy training was studied in a pre-post test design ; measurements were conducted at baseline and after 12 weeks of therapy . The pretreatment scores of the patients with apraxia were compared to normscores and scores of a control group of patients without apraxia ( n = 36 ) to investigate which impairments are present . The following variables were analysed in order to determine which factors influence outcome : additional neuropsychological deficits ( comprehension of language , cognitive impairments due to dementia , neglect and short term memory ) , level of motor functioning , severity of apraxia and performance on activities of daily living ( ADL ) , and some relevant patient characteristics ( gender , age , type of stroke , time since stroke , and location of treatment ) . Results : The results showed that the presence of apraxia is associated with the presence of additional cognitive and motor impairments . The successful outcome of strategy training was not negatively influenced by cognitive comorbidity . The outcome seemed to be more prominent in patients who were more severely impaired at the start of rehabilitation in terms of the degree of motor impairments , the severity of apraxia and the initial ADL dependence . The ADL observations , however , displayed a ceiling effect , which was taken into account in discussing the results . Demographic variables , especially age , did not predict the outcome of treatment . Conclusions : We suggest that the effect of this training is stronger in more severely disabled patients . However , neither the presence of additional cognitive impairments nor the severity of motor problems nor old age should be an indication for refraining from treating apraxia Depression is a common condition among long-term care residents with limited treatment options available . There are few nonpharmacological interventions available to this population . This study examined the use of a prescribed , therapeutic recreation-nursing intervention , wheelchair biking , for treatment of symptoms of depression in older adults in a long-term care setting . A classical experimental design was used and was guided by the Roy Adaptation Model . Forty residents were pretested for depression and r and omly assigned to two groups . A 2-week trial of biking therapy was provided to the treatment group . All participants were posttested . Findings indicated there was a statistically significant improvement in depression scores for the treatment group and no significant change for the control group . This study contributes to the body of knowledge of nursing regarding options for the treatment of depression in older adults , and is an encouraging indicator that psychosocial interventions may be effective in reducing depression Assisted walking and walking combined with conversation were compared to a conversation-only intervention in nursing home residents with Alzheimer disease . Sixty-five subjects r and omly assigned to treatment group were tested at baseline and end of treatment . Subjects ' mean Mini-Mental State Examination score was 10.83 ; mean age was 87 . Treatment was given for 30 minutes three times a week for 16 weeks . Subjects in the assisted walking group declined 20.9 % in functional mobility ; the conversation group declined 18.8 % . The combined walking and conversation treatment group declined only 2.5 % . These differences in outcome were significant and appear to have been affected by differences in treatment fidelity . Subjects in the conversation treatment group completed 90 % of intended treatment compared with 75 % in the combined group and only 57 % in the assisted walking group . Failure to treat was due to subject refusal and physical illness . The conversation component of the combined walking and conversation treatment intervention appears to have improved compliance with the intervention , thereby improving treatment outcome . Results indicate that assisted walking with conversation can contribute to maintenance of functional mobility in institutionalized population s with Alzheimer disease . Staff assigned to this task should be prepared to use effective communication strategies to gain acceptance of the intervention Background : Balance training programs have not shown consistent results among older adults , and it remains unclear how different training methods can be adapted to frail elderly people . Objective : The purpose of this study was to investigate the effects of a 4-week visual feedback-based balance training on the postural control of frail elderly women living in residential care homes . Methods : Elderly women of two residential care facilities were r and omized to an exercise group ( EG , n = 20 ) and to a control group ( CG , n = 7 ) . The EG participated in training sessions three times/week for 4 weeks . The exercises were carried out with a computerized force platform with visual feedback screen . The dimensions of balance function studied were st and ing body sway , dynamic weight shifting , and Berg Balance Scale performance . Results : The EG showed significant improvement in balance functions . The performance time in dynamic balance tests improved on average by 35.9 % compared with a 0.6 % increase in the CG ( p = 0.025–0.193 ) . The performance distance in these tests decreased on average by 28.2 % in the EG as compared with a 9.8 % decrease seen in the CG . The Berg Balance Scale performance improved by 6.9 % compared with a 0.7 % increase in the CG ( p = 0.003 ) . The st and ing balance tests in the more dem and ing st and ing positions showed improvements in the EG , whereas similar changes in the CG were not found . Conclusions : Our findings suggest that balance training based on visual feedback improves the balance control in frail elderly women living in residential care , also enhancing the performance of functional balancing tasks relevant to daily living . The subjects were motivated to participate in the training , as indicated by the high compliance ( 97.5 % ) with the program The purpose of this research was to explore the role of exercise in preventing falls , specifically assessing the effectiveness of an ankle strengthening and walking program to improve balance , ankle strength , walking speed , and falls efficacy and to decrease falls and subjects ' fear of falling . Sixteen individuals participated in the study which was conducted at two nursing homes . Subjects were assigned r and omly to an intervention or control group . The participants in the intervention group completed a 3-month supervised program of ankle strengthening exercises and walking . Descriptive statistics were used to characterize the sample , and differences in the least square means were used to assess the outcome variables ( i.e. , balance , ankle strength , walking speed , falls , fear of falling , falls efficacy ) before the exercise program , and again at 3 months and 6 months after the program for the intervention and control subjects . Findings for the intervention group from pretest to 3-month posttest were , for the most part , maintained or in the predicted direction , suggesting that regular exercise shows promise for preventing deterioration and improving fall-related outcomes for elderly nursing home residents The purpose of this experimental study was to compare the effects of skill training , a traditional stimulation approach , and regular care ( control group ) on the ability to perform the basic activities of daily living of nursing home residents with dementia . Sixty-three subjects were r and omly selected and r and omly assigned to the three groups . Ability to perform the basic activities of daily living ( ADLs ) and progress toward meeting individually set ADL-related goals were measured . Significant differences were found in two of the three measures used . In general , the greatest improvement was found in the skill training group , modest improvement in the simulation group , and decline in the control group OBJECTIVE The purpose of this pilot was to determine whether a strength and flexibility program in frail long-term care facility ( LTC ) residents would result in improved function . DESIGN A prospect i ve , r and omized , controlled , semicrossover trial was design ed with participants assigned either to group exercise ( EX ) or recreational therapy ( C ) . In the EX group , the intervention continued for 1 year . In the C group , recreation continued for 6 months ; these controls were then crossed over to the same exercise intervention as the EX group and followed for an additional 6 months . Functional outcomes were measured at baseline and 3 , 6 , 9 , and 12 months for both groups . SETTING A LTC facility , which included both assisted living ( AL ) and nursing home ( NH ) residents . PARTICIPANTS Twenty frail residents ( 5 from NH , 15 from AL ) aged 75 to 99 years at one LTC facility . INTERVENTION After r and om group assignment , the EX group met 1 hour three times per week . An exercise physiologist and LTC staff conducted sessions which included seated range of motion ( ROM ) exercises and strength training using simple equipment such as elastic resistance b and s ( therab and s ) and soft weights . The C group met three times per week and participated in activities such as painting during the first 6 months , before crossing over to exercise . MEASUREMENTS AND METHODS Objective measures of physical and cognitive function were obtained at baseline and 3 , 6 , 9 , and 12 months using the timed get-up- and -go test ( TUG ) , Berg balance scale , physical performance test ( PPT ) , and mini-mental status exam ( MMSE ) . Because we were interested in the impact of exercise on multiple endpoints and to protect the type I error rate , a global hypothesis test was used . RESULTS There was a significant overall impact across the four measures of the exercise intervention ( P = 0.013 ) . Exercise benefit as indicated by the difference between exercise and control conditions showed exercise decreased TUG by 18 seconds , which represents an effect size ( in st and ard deviation units ) of 0.50 , increased PPT scores by 1.3 , with effect size = 0.40 , increased Berg scores by 4.8 , with effect size of 0.32 , and increased MMSE by 3.1 , with effect size = 0.54 . Except for the Berg , 90 % confidence intervals on these exercise effects excluded 0 . CONCLUSION Frail elderly in a LTC facility were able to participate and benefit from a strength training program . The program was delivered with low-cost equipment by an exercise physiologist and LTC staff . The advantage of such a program is that it provides recreational and therapeutic benefits OBJECTIVE Resistance and endurance training result in gains in fitness in the aged . It is unclear whether the debilitated elderly can perform moderate-intensity training and whether such training results in short-term improvements in strength , endurance , and function in this population . DESIGN R and omized , controlled trial . SETTING S AND PATIENTS Subjects were from a Veterans Affairs nursing home and rehabilitation unit and a community nursing home . They were older than 60 yrs with impairment in at least one physical activity of daily living . Seventy-eight subjects volunteered and 58 ( mean age , 75 yrs ; 9 women , 49 men ) completed the intervention and initial posttest . Only one subject withdrew because of injury or disinterest . INTERVENTION Thrice-weekly resistance training ( using an isokinetic dynamometer ) and twice-weekly endurance training for 4 to 8 weeks . MAIN OUTCOMES Isometric strength in dominant arm and leg , heart rate response to timed endurance test , and activities of daily living score . RESULTS The mean change in isometric strength across the muscle movements tested was 32.8 % in the training group and 10.2 % in the control group ( difference , 22.6 % ; 95 % confidence interval , 6.2 % to 39.0 % ) . No change in heart rate during exercise was seen in the training group . Trained subjects tended to have a greater improvement in functional activity than control subjects , which was statistically significant ( p = .04 ) for those subjects who at enrollment were most dysfunctional ( i.e. , activities of daily living score less than 13 [ maximum score 26 ] ) . CONCLUSION This group of debilitated elderly patients effectively performed resistance training and increased their strength , with the most impaired gaining the most function . Few in the group could effectively perform endurance training CONTEXT Falls are a major health problem in nursing homes , but no interventions have been shown to prevent falls in nursing home residents . OBJECTIVE To evaluate an intervention program design ed to prevent falls and associated injuries in high-risk nursing home residents . DESIGN R and omized controlled trial . SETTING AND PARTICIPANTS Seven pairs of middle Tennessee nursing homes with 1 facility in each pair r and omly assigned to the intervention . Facilities had 482 ( 261 control , 221 intervention ) residents who qualified for the study because they had high risk of falls and a potential safety problem that could be addressed by the intervention . INTERVENTION Comprehensive structured individual assessment with specific safety recommendations that targeted suboptimal practice s for environmental and personal safety , wheelchair use , psychotropic drug use , and transferring and ambulation . Facility staff were encouraged to implement the individual recommendations and to improve overall facility safety . MAIN OUTCOME MEASURES The mean proportion of recurrent fallers and incidence rate of injurious falls in the facility in the year following the intervention . RESULTS The mean proportion of recurrent fallers in intervention facilities ( 43.8 % ) was 19.1 % ( 95 % confidence interval , 2.4%-35.8 % ) lower than that in control facilities ( 54.1 % , P=.03 ) . Intervention facilities had a nonsignificant trend toward a lower mean rate of injurious falls ( 13.7 vs 19.9 per 100 person-years , reduction of 31.2 % , P=.22 ) . Subgroup analyses suggested greatest benefits for residents for whom the recommended interventions were carried out or who had 3 or more falls in the preceding year . CONCLUSION The high rate of falls and related injuries in nursing homes should not be viewed as inevitable , but as outcomes that can be substantially improved through structured safety programs Context In frail older people living in residential care facilities , hip protectors reduce fall-related femoral and pelvic injuries . In older people living in the community , prevention programs that target exercise and fall-related risk factors reduce falls and injuries . In older people living in residential care facilities , fall prevention programs , other than the use of hip protectors , have had mixed results . Contribution This r and omized trial shows that a multidisciplinary fall prevention program reduces falls and femoral fractures in older people living in residential care facilities . The program included general as well as resident-specific , tailored strategies . Editors ' Note The Cochrane Library ( Issue 3 , 2001 ) has two systematic review s that summarize r and omized trial evidence about interventions to prevent falls . The Editors Falls are a major problem in older people ( 1 , 2 ) . Hip fractures result ing from falls are particularly common in elderly persons living in residential care facilities ( 3 , 4 ) ; they account for a substantial proportion of dependency and mortality ( 5 ) . During the past decade , r and omized , controlled trials study ing fall prevention have shown both positive and negative results ( 6 - 8 ) . Differences in target groups , interventions , and outcome measures may explain the inconsistent results . In residential care facilities and nursing homes , only one trial demonstrated that intervention programs may help prevent falls ; however , this trial studied only people who fell repeatedly ( 9 ) . Other trials have not shown reductions in falls or injuries ( 10 - 13 ) but have shown fewer hospital admissions ( 11 ) and improvements in mobility ( 12 ) , visual acuity , and hypotension ( 13 ) . The use of hip protectors has consistently proved effective in preventing hip fractures in selected high-risk population s ( 14 ) . Some trials that have included cognitively healthier older people in the community have shown reduced falls and injuries when specific risk factors are targeted ( 15 - 18 ) . However , evidence is lacking for older people living in institutions ( 19 ) . We hypothesized that an intervention program that targeted multiple risk factors for falls in older people living in residential care facilities , in particular those with a high risk for falling , would reduce falls and fall-related injuries . We therefore conducted a cluster r and omized trial for preventing falls in nine residential care facilities . Methods Design Study participants were older people living in residential care facilities located in Ume , a city in northern Sweden . The selected facilities had to have more than 25 residents . The nine that met this criterion were divided into group A and group B. The distribution was based on the age and number of residents , type of setting ( care and service offered as well as corridor or private home design ) , and record of previous falls as routinely reported to the local authority . To keep the groups distinct from one another , the physicians , registered nurses , physical therapists , and occupational therapists who were responsible for working with the residents in group A could not also work with group B residents . Group A consisted of four facilities that accommo date d 224 residents ; the facilities had 29 to 74 residents each , and the median age by facility ranged from 82 to 85 years . Group B consisted of five facilities with a total of 215 residents ; there were 31 to 66 residents per facility , and the median age by facility ranged from 79 to 85 years . The number of falls reported to the local authorities in the 2.5 years preceding the trial was similar for both groups : 1.26 per resident per year for group A and 1.29 for group B. After baseline assessment of all residents , groups A and B were r and omly assigned by lots to an intervention or a control group ( Figure 1 ) . The r and om allocation was conducted by a person with no knowledge of the study . Two sealed , dark envelopes were used . In each envelope , a letter specified one of the groups . Before the lot was drawn , the first envelope drawn was design ated as the intervention group . The local authorities , residents , staff of the nine facilities , and the research group were then informed of the results of the r and omization . Figure 1 . Study design . All residents in the study received written and oral information . All participants ( or the relatives and guardians of participants with severe cognitive dysfunction ) gave informed consent . The administrators and staff of the nine facilities involved also received information about the study and agreed to participate . The Ethics Committee of the Medical Faculty of Ume University approved the study . Definition of a Fall and an Injury A fall was defined as an event in which the resident unintentionally came to rest on the ground or floor , regardless of whether an injury was sustained . Thus , this definition also includes falls that result ed from acute illness or epileptic seizure and incidents that result ed in a resident 's falling and being found on the floor by staff or another resident . An injury was defined according to the Abbreviated Injury Scale ( 20 ) . Classifications were minor for injuries limited to superficial wounds and bruises ; moderate for intermediate-level injuries , such as vertebral and wrist fractures ; and serious for major fractures , such as hip fractures and other femoral fractures . Participants and Setting s All residents in the nine facilities who were 65 years of age or older were selected in a cross-sectional manner . Thirty-seven of these residents declined to participate , were admitted to hospitals , or died before r and omization . Sex and age of the 37 non participants were similar to those of the remaining 402 residents . In Sweden , older people living in residential care facilities are disabled by cognitive or physical impairment and thus require supervision , functional support , or nursing care . In this study , some residents lived in private apartments and others had private rooms but shared dining and living rooms . In all facilities , residents had 24-hour daily access to assistance with activities of daily living , household issues , and medical care . The median age was 83 years ( range , 65 to 100 years ) , and most residents were female ( 72 % ) . Few residents could walk outdoors without a walking aid ( 14 % ) or shower without assistance ( 18 % ) ; few were nonambulatory ( 19 % ) or entirely dependent when eating ( 8 % ) . Additional baseline characteristics are presented in the Table . Table . Baseline Characteristics of the 402 Residents Participating in the Study All members of the permanent staff , regardless of profession , participated in the study . In addition , eight physiotherapists were employed part-time ( a total of 200 h/wk ) until the end of the intervention period , and three physiotherapists were employed part-time ( a total of 10 h/wk ) during the follow-up period . A total of 273 nurses ' aides or licensed practical nurses and 20 registered nurses worked at the nine facilities . Baseline Assessment Each resident 's physician completed a question naire regarding clinical characteristics and drugs prescribed . A registered nurse reported delirium episodes ( Table ) . Physiotherapists interviewed and assessed all residents . Hearing was rated as impaired if the resident could not hear normal speech from a distance of 1 meter or used a hearing aid . Vision was rated as impaired when the resident , with or without glasses , could not read a word written in 5-mm capital letters at reading distance . Global cognitive function was screened by using the Mini-Mental State Examination ( MMSE ) ( 21 ) . Licensed practical nurses or nurses ' aides were interviewed to determine the number of falls that had occurred during the 6 months preceding the study and the extent of use of physical restraints . Activities of daily living were assessed according to the Barthel index ( 22 , 23 ) . All residents were screened for the risk for falling . First , by using the Mobility Interaction Fall Chart ( 24 ) , a resident was classified to be at higher risk for falling if he or she stopped walking when talking to an accompanying person ( 25 ) , walked more slowly when carrying a glass of water ( 26 ) , or had impaired vision or difficulty concentrating . Second , a physiotherapist globally rated the fall risk as higher if the resident showed risk-taking behavior considered to jeopardize balance . If the residents were not classified to be at higher risk for falling by any of these described measures , they were considered to be at lower risk for falling . Residents at higher risk were likely to be older than those at lower risk ( median age , 84 years [ range , 65 to 98 years ] vs. 83 years [ range , 65 to 100 years ] ) , to have lower MMSE scores ( median score , 17 [ range , 0 to 30 ] vs. 21 [ range , 0 to 30 ] ) , and to have more medical diagnoses ( median , 4 vs. 3 ) . The main areas of each facility were also screened according to a checklist for environmental hazards , such as lighting , flooring , obstacles inside the facility , and dangerous areas outside the facility ( for example , icy areas ) . Twelve residents in the control group and six in the intervention group died or moved during the 11-week intervention period ( Figure 1 ) . Intervention Program The intervention program comprised strategies that targeted both general and resident-specific risk factors for falling . The strategies were design ed to be meaningful to the residents without compromising mobility . The 89 residents screened as being at higher risk as well as the 19 residents at lower risk who fell during the 11-week intervention period were the focus of the individualized intervention program . Increasing the staff 's knowledge about fall prevention was believed to be the starting point of a process that would produce long-term results . Staff Education All staff were invited to a 4-hour educational session , and more than half attended . The sessions were led by a physician and a physiotherapist and covered risk factors for falls and intervention OBJECTIVE To study the acute effects of non-strenuous physical exercise on memory retrieval and visuo-motor performance in old-old nursing home residents . DESIGN A r and omized control trial . SETTING A nursing home . PARTICIPANTS Ambulatory volunteers from the nursing home , with all 20 shown to be normal on mental status . Three were male and 17 female , with a means of 84.5 years for age and 9.3 years for education . They were divided at r and om into an exercise and a control group . INTERVENTION A single 15-minute st and ardized bout of non-strenuous exercise administered independently to each participant in the exercise group . Control group participants watched a video of similar exercises for 15 minutes . MEASUREMENTS Two measures requiring the retrieval of category instances with semantic or initial consonant cues . Retrieval time was 60 seconds for each of four categories per measure . Visuo-motor performance was measured by Symbol Digit coding . Testing sessions were held before exercise , immediately post-exercise and 30 minutes post-exercise . RESULTS The group-by-time interaction was significant only for semantically cued memory ( P < 0.01 ) , with higher retrieval at post-testing only in the exercised group . The higher retrieval was mainly attributable to more new items retrieved by the exercise group at the immediate post-test ( P < 0.05 ) . CONCLUSIONS This study provides preliminary support for the hypothesis that non-strenuous physical exercise has positive acute effects on meaningfully cued memory Objective : To establish the effect of a short , individualized exercise programme on balance dysfunction in the elderly . Design : A single-blind , r and omized , controlled , multicentre trial . Setting : Physical and recreational therapy departments from two rehabilitation centres . Participants : Ninety-four subjects of ≥75 years with functional balance problems living independently or in a residential care facility . Seventy-seven subjects completed the intervention period and four-week follow-up . At a one-year follow-up 49 subjects were evaluated on balance functioning . Interventions : Twelve sessions of an individualized balance training programme ( experimental group ) or 12 sessions of an individualized extra attention programme ( control group ) given in 4–6 weeks . Main outcome measures : Berg Balance Scale and the Dynamic Gait Index to establish balance functioning , a visual analogue scale to establish fear of falling in daily life and the Hospital Anxiety Depression Scale to verify feelings of anxiety and depression . Results : Subjects in the experimental group improved significantly more on the Berg Balance Scale and the Dynamic Gait Index than those in the control group ( p ≤ 0.001 , p ≤ 0.001 , respectively ) . However the effect disappeared at a one-year follow-up on the Berg Balance Scale . No prognostic factors could be identified to determine who would benefit most from the individualized exercise programme . Results on the other response variables revealed no effect of the intervention . Conclusion : A short individualized exercise programme can improve functional balance in people aged 75 years and older . This improvement was maintained at least for one month but had worn off by one year AIM This paper reports an evaluation of a range-of-motion exercise programme aim ed at improving joint flexibility , activity function , perception of pain , and depressive symptoms in a sample of stroke survivors in long-term care facilities . BACKGROUND The benefits of physical rehabilitation for stroke survivors have been well established . There is , however , little empirical data on the effects of a simple nurse-led range-of-motion exercise programme in improving function for these people . METHOD A r and omized controlled trial was conducted in 1999 with 59 bedridden older stroke survivors in residential care . Participants were r and omly assigned to usual care or one of two intervention groups . The 4-week , twice-per-day , 6 days-per-week range-of-motion exercise protocol s were similar in both intervention groups , and consisted of full range-of-motion exercises of the upper and lower extremities . To test the effect of different degrees of staff involvement , in intervention group I , a Registered Nurse was present to supervise participants performing the exercises , while intervention group II involved a Registered Nurse physically assisting participants to achieve maximum range-of-motion within or beyond their present abilities . RESULTS Both intervention groups had statistically significant improvement in joint angles , activity function , perception of pain and depressive symptoms compared with the usual care group ( P < 0.05 ) . Post hoc comparison revealed that the joint angles in intervention group II were statistically significantly wider than in both the other groups ( P < 0.01 ) . CONCLUSIONS A simple nurse-led range-of-motion exercise programme can generate positive effects in enhancing physical and psychological function of bedridden older people with stroke . Further studies are needed to investigate the long-term effects of the programme in maximizing function , reducing care utilization and enhancing quality of life for this population OBJECTIVE To examine the applicability and feasibility of an intervention directed at improving continence , endurance , and strength ( Functional Incidental Training [ FIT ] ) , for older patients in Veterans Administration ( VA ) nursing homes . DESIGN Data were collected during a r and omized , controlled , crossover trial . SETTING Four VA nursing homes . PARTICIPANTS All 528 patients in the nursing homes were screened , 178 were eligible , and 107 were r and omized into the trial . A total of 64 participants completed the intervention phase of the trial . INTERVENTION Trained research staff provided the FIT intervention , which included prompted voiding combined with individualized , functionally oriented endurance and strength training exercises offered four times per day , 5 days per week , for 8 weeks . MEASURES Descriptive data were collected relevant to the translation of the FIT intervention into everyday practice , including number of patients eligible and reasons for in eligibility , attrition rates and reasons for attrition , participant adherence to and satisfaction with FIT , and the costs of FIT relative to usual care . RESULTS One third of the 528 patients met the eligibility criteria . The major reasons for in eligibility were being continent , age under 60 , and a short anticipated length of stay . Of the 146 patients enrolled in the trial , 85 ( 58 % ) dropped out during the 9- to 10-month project . Deterioration in health status , death , and discharge accounted for two thirds of the attrition . Adherence to FIT was in general high but variable . Participants completed prompted voiding plus at least one exercise in 75 % of the FIT rounds offered . Of the 60 participants who completed the protocol and who could answer simple questions , 75 % indicated they enjoyed FIT , but 62 % indicated that the exercise was too frequent , and 28 % indicated they were offered opportunities to toilet too often . Based on timed observations , the costs of FIT are about four times as high as usual continence care . CONCLUSIONS FIT is applicable to a substantial number of patients in VA nursing homes . The FIT protocol tested in this trial can be further refined and individualized based on patient preferences and adherence to various components of FIT in order to make it more feasible , efficient , and cost-effective in practice . The costs of maintaining an intervention such as FIT in all VA nursing home patients who may benefit , however , are high and must be justified largely by potential positive effects on function and quality of life , as opposed to cost savings result ing from the intervention The purpose of this study was to determine the influence of simple , progressive lower body exercise training , focusing on strength and power , on functional abilities in frail older adults . Twenty-five residents of a long-term care facility ( 75 - 94 yrs ) participated in this r and omized controlled trial of 10-wks duration . The exercise group ( Ex , n = 18 ) underwent simple , progressive lower body resistance exercises , specifically aim ed at improving muscle power , 3 times/wk ; the control subjects ( Con , n = 7 ) maintained their usual daily activities . Knee extensor strength and power were measured on an isokinetic dynamometer ( 180 degrees/s ) , and functional performance was assessed from a 6-m walk timed test , a 30-s chair st and , and an 8-ft up- and -go timed test , before and after the 10-wk intervention period . Significant increases were found in the Ex group for eccentric ( 44 % ) and concentric ( 60 % ) average power ( p < 0.05 ) , and improvements were seen on each functional test : the 8-foot up- and -go , chair st and , and walk time improved by 31 % , 66 % , and 33 % , respectively ( p < 0.05 ) . No significant change occurred in the Con group . In conclusion , simple progressive exercise training , even in the 10th decade , increases muscle power and is associated with an improved performance of functional activities using the trained muscles Twenty-eight subjects with chronic age-related disabilities living in the nursing home"Istituto di Riposo per la Vecchiaia " in Torino were assigned to a pet-therapy intervention group , consisting of 3/week sessions of almost one-hour visit for 6 weeks with a little cat , of to a control group undergoing usual activity programs . The purpose of this study was to evaluate the effects of pet-therapy on nursing home in patients . There were no differences in demographic or clinical characteristics and in mean duration of institutionalization between the two groups . Results showed that patients with animal interaction had improved depressive symptoms and a significant decrease in blood pressure values . The pet-therapy programs are desirable components of the multidisciplinary treatment for frail elderly patients in long-term care OBJECTIVE To evaluate an exercise protocol design ed to improve strength and mobility , and to decrease injury risk factors in physically restrained nursing home residents . DESIGN A r and omized controlled trial . PARTICIPANTS Ninety-seven residents were r and omized into either exercise or control groups . Thirty-five exercise and 37 control group residents completed all post- assessment s after a 9-week trial . INTERVENTION Walking or wheelchair movement training was supplemented by rowing exercise three times per week . Practice in behaviors related to safe movement was provided incidental to the exercise . MEASUREMENT Endurance , speed , and injury risk measures relevant to walking , wheelchair propulsion , and st and ing were assessed by st and ardized protocol s. Rowing endurance , rowing range of motion , and h and grip strength measures were collected to assess the effect of the rowing component of the exercise protocol . RESULTS Fifty-four percent of the subjects who provided consent did not complete the protocol because of health status changes , lack of cooperation , or physical limitations that precluded exercise . The subjects who completed the exercise program showed significant improvement on injury risk and measures related to upper body strength ( h and grip strength , rowing endurance , wheelchair endurance , and speed ) . Measures related to lower body strength did not significantly improve . CONCLUSION Physically restrained residents are very frail , and it is difficult to implement a long-term exercise program with many residents because of the frailty . However , a substantial proportion of residents did cooperate well with the exercise program and showed improvement on measures correlated with decreased injury risk . The exercise program could be easily modified to include more lower body exercise , and the result ant protocol would be an important adjunct to restraint reduction programs OBJECTIVE To determine if an exercise intervention , Functional Incidental Training ( FIT ) , results in improvements in mobility endurance and physical activity when compared with prompted voiding ( PV ) among cognitively and mobility impaired nursing home residents . DESIGN Residents from four nursing homes were r and omized into either a PV only ( PV ) or a PV plus FIT ( FIT ) intervention group for 8 weeks . Research staff implemented all intervention and measurement protocol s. PARTICIPANTS Seventy-six incontinent nursing home residents completed all phases of the trial . MEASURES The st and ing , walking , and wheelchair endurance , physical activity , and frequency of agitation of all residents were assessed before , during , and after the 8-week intervention . RESULTS The average length of time that subjects could walk or wheel was 2.6 and 4.6 minutes , respectively , at baseline . There was a significant group x time interaction after intervention , with only the FIT group showing improvements in walking , wheelchair , and st and ing endurance ( Manova F = 4.56 , 2.62 , and 5.98 , respectively ; P < .05 in all cases ) . The frequency with which agitation was observed showed a significant drop over time in both groups ( F = 14.3 , P < .001 ) , with no significant group x time interaction . CONCLUSION The FIT intervention , which requires 6 minutes more nurses ' aide time than does PV , increases both physical activity and mobility endurance in extremely frail and deconditioned nursing home residents . The increased cost of this intervention must be evaluated both in terms of clinical outcomes and by the reality that the target group for this intervention is very frail and will continue to require nursing home care , even assuming an excellent response to the intervention This study tested a 3-month ankle-strengthening and walking program design ed to improve or maintain the fall-related outcomes of balance , ankle strength , walking speed , risk of falling , fear of falling , and confidence to perform daily activities without falling ( falls efficacy ) in elderly nursing home residents . Nursing home residents ( N = 81 ) between the ages of 64 and 100 years participated in the study . Two of the fall-related outcomes , balance and fear of falling , were maintained or improved for the exercise group in comparison to the control group Background : Falls are a major cause of morbidity in old age . A small number of fall prevention trials in cognitively intact community-dwelling older people have been effective . This study set out to examine the preventability of falls in older people living in institutional care . Objective : To evaluate the effectiveness of falls risk factor assessment /modification and seated balance exercise training in reducing falls among elderly people living in residential care . Methods : 133 residents with a mean age of 84± ( SD ) 6.8 years were allocated at r and om by home to receive either a 6-month falls risk factor assessment /modification and seated balance exercise training programme ( n = 77 ) or 6 months of reminiscence therapy ( n = 56 ) . The risk factors targeted were postural hypotension , polypharmacy , visual acuity , and ambient lighting levels . Falls risk factor assessment s and recommendation for modifications were performed at baseline in the intervention group and assessment s repeated at 6 months . Functional reach , reaction time , timed up- and - go , grip strength , spinal flexibility , and Philadelphia Geriatric Centre Morale Scale and Mini-Mental State Examination scores were determined at baseline and at 6 months by a ‘ blind ’ observer . Falls and fractures were then monitored in both groups during a 7- to 12-month falls-monitoring follow-up period . Results : Only 90 of 133 ( 67.7 % ) residents completed the 6-month intervention period , and 84 ( 63.2 % ) completed the 7- to 12-month falls-monitoring follow-up period . Both prevalence of postural hypotension ( p = 0.0005 ) and poor visual acuity ( p = 0.04 ) were reduced in the intervention group . There was no difference between the groups in the number of falls sustained , the risk of falling [ odds ratio 0.45 ( 95 % CI 0.19–1.14 ) ] , or in the risk of recurrent falling [ odds ratio 1.07 ( 95 % CI 0.40–2.97 ) ] . No significant differences were found between the groups with regard to change in other outcome measures . Conclusions : The high drop-out rate reduced the power of this study to detect any effect of the interventions used . It is possible that either the exercises were not sufficiently vigorous or that to improve balance exercises must be performed st and ing . Further research is required to identify effective fall prevention strategies for elderly people in residential setting Reduction in muscle mass and physical function depends on a variety of interacting factors : age , physical activity level , nutritional state and the type and impact of disease . The aim of this study was to investigate the effect of an individualized moderate intensity physical training program on muscle strength , balance , mobility , ambulation and activities of daily living ( ADL ) in institutionalized elderly people aged 65 and over with multiple diagnoses . Baseline assessment s consisted of strength , balance , mobility/ambulation , and ADL . Twenty-one subjects were included in the intervention program . A control group ( 21 subjects ) was first matched in pairs according to gender , age , ADL and mobility , and then by balance , ambulation and strength . The intervention program was individualized and included strength , mobility , balance and endurance training . Follow-up measures were conducted directly after the intervention and 10 weeks later . After drop-out , 20 subjects in the intervention group and 15 subjects in the control group remained for analyses . Balance and mobility improved significantly in the intervention group while declining in the control group . This pilot study indicates that a physical training program may improve functional capacity for institutionalized elderly persons with multiple diagnoses The primary aim of the study was to test the hypothesis that depression severity in care homes for older people would be reduced by an occupational therapy programme . This was a feasibility study for a cluster r and omised controlled trial and involved four intervention and four control homes in northern Engl and . In each intervention home a registered occupational therapist worked full-time for one year delivering an individualised programme to participants . Pre- and post-intervention data for the Geriatric Mental State – Depression Scale ( primary outcome measure ) were obtained for 143 participants . Secondary outcomes included dependency and quality of life . No significant intervention effects were found in any of the quantitative outcome measures , though qualitative interviews showed the intervention was valued by many participants , staff and relatives . Therapist ratings and qualitative interviews suggested that the intervention was beneficial to some participants but no distinctive characteristics were found that might enable prediction of likely benefit on initial assessment . This exploratory study provides no evidence that this intervention produced benefits in terms of depression , dependency or quality of life . Lack of prior power calculations means these are not definitive findings ; but numbers were sufficient to perform the required analyses and data did not suggest effects that would have reached statistical significance with a larger sample . This study highlights issues for consideration in providing such services in care homes OBJECTIVE To determine the effect of a home exercise program on strength , postural control , and mobility following hip fracture . DESIGN R and omized controlled trial of 1 month 's duration . SETTING Daily exercise carried out within the subjects ' home environments . PARTICIPANTS Forty-two people 64 to 94 years of age , 35 of whom were living independently in the community and 7 of whom were residing in institutional care . Subjects were recruited on average 7 months after a fall-related hip fracture and r and omly allocated to either the intervention or the control group ( n = 21 each ) . The groups were well matched in terms of medical conditions , medication use , disability , and activity levels . INTERVENTION A " home-based " program of weight-bearing exercise established at a visit by a physiotherapist . MAIN OUTCOME MEASURES Quadriceps strength , postural sway , functional reach , weight-bearing ability , walking velocity , and self-rated fall risk . The subjects undertook these assessment s at the beginning and end of the trial . RESULTS At pretest , exercisers and controls performed similarly in all tests . At the end of the trial , the intervention group showed significantly greater quadriceps strength in the affected ( hip-fractured ) leg and increased walking velocity . The intervention subjects also improved their weight-bearing ability and reported reduced subjective falls risk . In contrast , there were no significant improvements in any of the test measures in the controls . Within the intervention group , improvements in quadriceps strength were significantly associated with improved performances in the weight-bearing test measures and with increased walking velocity . CONCLUSIONS This exercise program improved strength and mobility following hip fracture . Further research is needed to ascertain whether the extent of this improvement in these fall risk factors is sufficient to prevent falls Twenty-three geriatric patients from a mental institution were r and omly assigned to three groups-a social group , an exercise group , and a control group . Subjects participated in the study for 12 weeks . Heart rate at rest , exercise and recovery , balancing ability , total daily activity level ( diary method ) , and a self-care inventory were recorded for analysis . Data were collected at the start , the 8th and 12th weeks of the study , and 4 weeks after the termination of treatment . A Groups X Sex X Measurement Period factorial design , using multivariate analysis of variance tested the effect of the three factors . The trials effect was significant , as were several univariate tests for the sex effect and group by sex interaction . Data were discussed in terms of programmed physical activity for geriatrics , its value , and the limitations of evaluating such behavior in geriatric population OBJECTIVES To determine if two physical activity programs of varying intensity would result in improved sleep among incontinent and physically restrained nursing home residents . DESIGN Controlled trials of two physical activity programs . SETTING Seven community nursing homes in the Los Angeles area . PARTICIPANTS Residents were included if they had urinary incontinence or were physically restrained . Sixty-five subjects were studied . Mean age was 84.8 years , 85 % were female , mean length of residency in the nursing home was 19.9 months , and mean Mean Mini-Mental State Exam score was 13.1 . INTERVENTION The first physical activity program involved sit-to-st and repetitions and /or transferring and walking or wheelchair propulsion . These activities were performed every 2 hours during the daytime , 5 days per week for 9 weeks . The second , less frequent physical activity program involved rowing in a wheelchair-accessible rowing machine plus walking or wheelchair propulsion once per day three times per week for 9 weeks . MEASUREMENTS The physical function measures reported here include mobility endurance ( maximum time walking or wheeling ) and physical activity as measured by motion sensors ( Caltrac ) . Nighttime sleep was estimated by wrist activity monitors . Nighttime sleep measures included total time asleep , percent sleep , average duration of sleep , and peak duration of sleep . Daytime sleep was measured by timed behavioral observations of sleep versus wakefulness performed every 15 minutes during the day . RESULTS Nighttime sleep was markedly disrupted in both groups at baseline . Across all subjects at baseline , the average total sleep time was 6.2 hours and the percent sleep was 72.0 % , but the average duration of sleep episodes was only 21.2 minutes and the peak duration of sleep episode averaged only 83.8 minutes . During the daytime , subjects were observed asleep during 14.5 % of observations . Although there was improvement in mobility endurance in the intervention subjects compared with controls ( MANOVA F = 4.36 , P = .042 ) , there were no differences in the night and day sleep measures at follow-up testing . Even among a subgroup of intervention subjects who showed a 30 % or greater improvement in mobility endurance , sleep did not improve at follow-up compared with baseline . CONCLUSION This study supports our previous findings of marked sleep disruption in impaired nursing home residents . In addition , despite documented improvements in physical function with activity , we did not find improvements in sleep in the intervention versus control groups . These results suggest that increasing daytime physical activity alone is not adequate to improve sleep in impaired NH residents . Future efforts to improve sleep in this population should take into account the multifactorial nature of sleep disruption , including individual health problems that effect sleep and the disruptive nature of the nighttime NH environment Shimada H , Obuchi S , Furuna T , Suzuki T : New intervention program for preventing falls among frail elderly people : The effects of perturbed walking exercise using a bilateral separated treadmill . Am J Phys Med Rehabil 2004;83:493–499 . Objective : To determine the effects of a perturbed walking exercise using a bilateral separated treadmill in physically disabled elderly . Design : Participants of the study were 32 long-term care facility residents and out patients aged 66–98 yrs . Participants were r and omly assigned to a usual exercise group or to a treadmill exercise group . Perturbed gait exercise on a treadmill continued for 6 mos . Number of falls and time to first fall during a 6-mo period , balance and gait functions , and reaction time were evaluated before and after intervention . Results : The treadmill exercise group showed significant improvement in balance and reaction time when compared with the usual exercise group . Number of falls in the treadmill exercise group was 21 % lower than that in the usual exercise group . However , this difference was not significant . No significant differences were seen in time to first fall . Conclusions : Gait training with unexpected perturbation seems to have a beneficial impact on physical function in disabled elderly individuals . The results suggest that this program may be used as an exercise intervention to reduce falls in institutional setting BACKGROUND Although disuse of skeletal muscle and undernutrition are often cited as potentially reversible causes of frailty in elderly people , the efficacy of interventions targeted specifically at these deficits has not been carefully studied . METHODS We conducted a r and omized , placebo-controlled trial comparing progressive resistance exercise training , multinutrient supplementation , both interventions , and neither in 100 frail nursing home residents over a 10-week period . RESULTS The mean ( + /- SE ) age of the 63 women and 37 men enrolled in the study was 87.1 + /- 0.6 years ( range , 72 to 98 ) ; 94 percent of the subjects completed the study . Muscle strength increased by 113 + /- 8 percent in the subjects who underwent exercise training , as compared with 3 + /- 9 percent in the nonexercising subjects ( P < 0.001 ) . Gait velocity increased by 11.8 + /- 3.8 percent in the exercisers but declined by 1.0 + /- 3.8 percent in the nonexercisers ( P = 0.02 ) . Stair-climbing power also improved in the exercisers as compared with the nonexercisers ( by 28.4 + /- 6.6 percent vs. 3.6 + /- 6.7 percent , P = 0.01 ) , as did the level of spontaneous physical activity . Cross-sectional thigh-muscle area increased by 2.7 + /- 1.8 percent in the exercisers but declined by 1.8 + /- 2.0 percent in the nonexercisers ( P = 0.11 ) . The nutritional supplement had no effect on any primary outcome measure . Total energy intake was significantly increased only in the exercising subjects who also received nutritional supplementation . CONCLUSIONS High-intensity resistance exercise training is a feasible and effective means of counteracting muscle weakness and physical frailty in very elderly people . In contrast , multi-nutrient supplementation without concomitant exercise does not reduce muscle weakness or physical frailty Fifty female subjects , aged 72 - 92 ( mean 82 ) years , were enrolled in a 12-week ( 36 classes ) exercise program aim ed at increasing postural stability . Subjects were residents of sheltered apartments , rest homes or nursing homes , well enough and mobile enough to participate in the classes . The subjects were r and omized into an exercise or a control group . Their postural sway , st and ing at rest on a force platform , was measured with eyes open and eyes closed . The groups were well matched in all respects . The results showed no improvement in the postural sway as a result of the exercise program . We hypothesize that increasing postural sway in the elderly represents a deterioration in , for the most part , the nervous system and may at this extreme of life indicate an irreversible loss of function . For this reason no improvement in postural sway may be possible |
13,506 | 26,392,127 | Smoking rates among people in addiction treatment are more than double those of people with similar demographic characteristics .
Smoking rates are also higher in people being treated for opiate dependence compared with people being treated for alcohol use disorder | AIMS Smoking prevalence is higher among people enrolled in addiction treatment compared with the general population , and very high rates of smoking are associated with opiate drug use and receipt of opiate replacement therapy ( ORT ) .
We assessed whether these findings are observed internationally . | Abstract Objective : To evaluate an experimental heroin maintenance programme . Design : R and omised trial . Setting : Outpatient clinic in Geneva , Switzerl and . Subjects : Heroin addicts recruited from the community who were socially marginalised and in poor health and had failed in at least two previous drug treatments . Intervention : Patients in the experimental programme ( n=27 ) received intravenous heroin and other health and psychosocial services . Control patients ( n=24 ) received any other conventional drug treatment ( usually methadone maintenance ) . Main outcome measures : Self reported drug use , health status ( SF-36 ) , and social functioning . Results : 25 experimental patients completed 6 months in the programme , receiving a median of 480 mg of heroin daily . One experimental subject and 10 control subjects still used street heroin daily at follow up ( difference 44 % ; 95 % confidence interval 16 % to 71 % ) . Health status scores that improved significantly more in experimental subjects were mental health ( 0.58 SD ; 0.07 to 1.10 ) , role limitations due to emotional problems ( 0.95 SD ; 0.11 to 1.79 ) , and social functioning ( 0.65 SD ; 0.03 to 1.26 ) . Experimental subjects also significantly reduced their illegal income and drug expenses and committed fewer drug and property related offences . There were no benefits in terms of work , housing situation , somatic health status , and use of other drugs . Unexpectedly , only nine ( 38 % ) control subjects entered the heroin maintenance programme at follow up . Conclusions : A heroin maintenance programme is a feasible and clinical ly effective treatment for heroin users who fail in conventional drug treatment programmes . Even in this population , however , another attempt at methadone maintenance may be successful and help the patient to stop using injectable opioids INTRODUCTION Numerous investigations have shown that premature discharge against medical advice from alcohol detoxification treatment is associated with poor outcome . The aim of the present study was to assess the risk of different possible influencing factors . PATIENTS AND METHOD 168 in- patients admitted for detoxification treatment were included in the study . All patients were detoxified using clome-thiazole and /or carbamazepine in individual , symptom-triggered dosages . Possible influencing factors were recorded using a st and ardised interview . RESULTS Cox regression revealed a lower risk of premature discharge being significantly asso-ciated with few preceding withdrawals , intoxication at admission and treatment with clomethiazole . Kaplan-Meier survival statistics showed a significantly lower risk only for being treated with clomethiazole ( premature discharge until day 7 : chi2=25.07 ; p<0.001 ; premature discharge until day 14 : chi2=5.19 ; p=0.023 ) . Other included demographic factors like daily intake of ethanol before admission , duration of alcohol dependence , age or smoking status were not associated with the risk of premature discharge . DISCUSSION The present findings show that pharmacotherapy with clomethiazole may positively influence the risk of premature discharge . This might be a consequence of the psychoactive properties of the drug which leads to positive reinforcement Because of a controversial view on the role of smoking in the recovery process of alcoholism , outcome data obtained for alcoholics who had been included in a long-term clinical trial with a putative anticraving drug were analyzed . To avoid unknown interactions between the drug under study and smoking behavior , only placebo-treated patients were evaluated in this investigation . After 12 months of rehabilitation , there was no significant difference regarding abstinence rate between 48 smoking alcoholics ( who reported that they smoked 32 cigarettes on average per day ) and 15 nonsmoking alcoholics ( 33 % vs. 20 % ) . However , smokers tended to be abstinent longer than nonsmokers ( 173 vs. 114 days ; P= .092 ) . This possible advantage might be related to nicotinic effects on central dopamine systems in smokers , as indicated by higher growth hormone secretion after apomorphine stimulation obtained in smokers , compared with findings for nonsmokers ( area under the curve during chronic intoxication : 2253 vs. 1247 microg/min/l ; P= .019 ) . Multivariate regression analysis revealed a decreasing effect of ethanol blood level ( P= .006 ) and the number of fullfilled International Classification of Diseases , 10th edition ( ICD-10 ) criteria of the alcohol dependence syndrome ( P= .012 ) on stimulated growth hormone secretion . In contrast , the reported number of smoked cigarettes per day had an increasing effect ( P= .034 ) , accounting for 6 % of the variance of growth hormone secretion . However , differences in outcome could also be explained by other clinical features as smokers , compared with nonsmokers , were more frequently males ( 78.3 % vs. 60.7 % ) and younger when studied at index episode ( mean age 44.45 vs. 48.21 years ; P= .054 ) , reported higher ethanol consumption in the month before hospital admission ( 262 g vs. 192 g ; P= .044 ) , and met more criteria for the ICD-10 alcohol dependence syndrome ( 6.6 vs. 6.0 ; P= .047 ) . Therefore , it can not be stringently inferred from our data that a possible advantage of smoking for alcoholism recovery is causally related to the effects of nicotine on cerebral systems or human behavior , as our findings had not been based on a r and omized design Background : To investigate the improvement in quality of life ( QoL ) of alcohol-dependent patients during a 3-week inpatient withdrawal programme , and to identify the sociodemographic , clinical and alcohol-related variables associated with baseline QoL on admission and with improvement of QoL during residential treatment . Methods : This prospect i ve , observational study included 414 alcohol-dependent patients , hospitalised for a period of 3 weeks . QoL was measured on admission and at discharge using the French version of the Medical Outcome Study SF-36 . The mean scores for each dimension and for the Physical and Mental Component Summary scores were calculated . Results : The mean scores per dimension and the mean Physical and Mental Component Summary scores were significantly lower on admission than at discharge ; the lowest scores being observed for social functioning and role limitations due to emotional problems . At discharge , the mean scores per dimension were similar to those observed in the French general population . Female gender , age > 45 years , living alone , working as a labourer or employee , somatic comorbidity , and the existence of at least five criteria for alcohol dependence according to the DSM-IV classification were associated with a low Physical Component Summary score on admission ; psychiatric comorbidity , the presence of at least five DSM-IV dependence criteria , smoking and suicidality were associated with a low Mental Component Summary score on admission . The increase in Physical and Mental Component Summary scores during hospitalisation was more marked when the initial scores were low . Apart from the initial score , the greatest improvement in Physical Component Summary score was seen in patients with a high alcohol intake and in those without a somatic comorbidity ; the increase in Mental Component Summary score was greatest in patients without psychotic symptoms and in those who abused or were dependent on illegal drugs . Conclusion : QoL improvement after a residential treatment was related to low QoL scores at admission . Improvement in physical component of QoL was related to baseline alcohol intake and good somatic status . Improvement in mental component of QoL was related to other drugs abuse/dependence This study examined the association between stopping smoking at 1 year after substance use treatment intake and long-term substance use outcomes . Nine years of prospect i ve data from 1185 adults ( 39 % female ) in substance use treatment at a private health care setting were analyzed by multivariate logistic generalized estimating equation models . At 1 year , 14.1 % of 716 participants who smoked cigarettes at intake reported stopping smoking , and 10.7 % of the 469 non-smokers at intake reported smoking . After adjusting for sociodemographics , substance use severity and diagnosis at intake , length of stay in treatment , and substance use status at 1 year , those who stopped smoking at 1 year were more likely to be past-year abstinent from drugs , or in past-year remission of drugs and alcohol combined , at follow-ups than those who continued to smoke ( OR=2.4 , 95 % CI : 1.2 - 4.7 and OR=1.6 , 95 % CI : 1.1 - 2.4 , respectively ) . Stopping smoking at 1 year also predicted past-year alcohol abstinence through 9 years after intake among those with drug-only dependence ( OR=2.4 , 95 % CI : 1.2 - 4.5 ) . We found no association between past-year alcohol abstinence and change in smoking status at 1 year for those with alcohol dependence or other substance use diagnoses when controlling for alcohol use status at 1 year . Stopping smoking during the first year after substance use treatment intake predicted better long-term substance use outcomes through 9 years after intake . Findings support promoting smoking cessation among smoking clients in substance use treatment Smoking is highly prevalent ( 85%-98 % ) in methadone maintenance treatment ( MMT ) patients . Methadone has been shown to increase cigarette smoking in a dose-dependent manner , whereas smoking/nicotine has been shown to increase methadone self-administration and reinforcing properties . The objective of this study was to evaluate methadone-nicotine interactions in MMT patients during trough and peak methadone effect conditions . Subjective effects of nicotine ( administered by cigarette smoking , 4 mg of nicotine gum and placebo gum ) and methadone and their combination were assessed in 40 regularly smoking , stabilized MMT patients using a r and omized , placebo-controlled , within-subject study design . Subjects responded to a battery of subjective assessment s before and after nicotine administration both before methadone administration ( cycles 1 and 2 ) and 3 hours after methadone administration ( cycles 3 and 4 ) . There was a main effect of methadone on the decrease of opioid withdrawal scores ( P < 0.001 ) , and cigarette smoking enhanced this effect ( day × methadone interaction , P = 0.031 ) . Both nicotine and methadone had main effects on the decrease of nicotine withdrawal scores ( P < 0.001 and P = 0.001 , respectively ) ; this was associated with the cigarette day ( day × nicotine interaction , P = 0.003 , and day × methadone interaction , P = 0.004 ) . Nicotine plasma levels were highest on the cigarette smoking day ( P < 0.001 ) . Methadone and nicotine shared main effects on the increase of ratings of euphoria and drug liking and on the decrease of restlessness , irritability , and depression . The overall results may help to explain high smoking rates in the MMT population and may account for reports of increased positive effects of methadone when the drugs are taken together BACKGROUND A r and omised controlled trial of substance misuse indicated that many patients who use methadone have respiratory symptoms and /or are prescribed respiratory medications . There is little research in this area . AIMS To determine the prevalence of respiratory disease and prescriptions among drug misusers . METHODS This historical cohort study of drug misusers and matched controls analysed routinely collected primary care data . The prevalence of common chronic respiratory diseases , class and number of respiratory medications were examined . RESULTS The cohort of 18,570 patients ( 9,285 per group ) was mostly male ( 64 % , n=11,890 ) and aged 31 - 59 years ( 76 % , n=14,060 ) . After adjusting for age , gender , deprivation and smoking status , the results showed that more drug misusers than controls had a diagnosis of asthma or chronic obstructive pulmonary disease ( 17.1 % vs. 10.9 % ; adjusted odds ratio ( OR ) 1.61 , 95 % confidence interval ( CI ) 1.46 to 1.77 , and 2.4 % vs. 0.8 % ; OR 1.86 , 95 % CI 1.42 to 2.44 , respectively ) and were prescribed more chronic respiratory medications : short-acting β(2)-agonists ( 16.4 % vs. 7.9 % ; OR 2.00 , 95 % CI 1.80 to 2.22 ) , long-acting β(2)-agonists ( 1 % vs. 0.4 % ; OR 1.93 , 95 % CI 1.29 to 2.89 ) , and inhaled corticosteroids ( 10.6 % vs. 7.6 % ; OR 1.49 , 95 % CI 1.33 to 1.67 ) . All differences were statistically significant ( p<0.001 ) . CONCLUSIONS Drug misusers have a significantly higher prevalence of respiratory diseases and respiratory prescriptions than matched controls . Further work is needed to determine the reasons for this The frequencies of structural chromosomal aberrations were analyzed in peripheral blood lymphocytes of 31 chronic alcoholics at the beginning of an intensive outpatient treatment program at a neuropsychiatric clinic and were compared with 31 controls matched for gender , age , smoking habits , and nondrinkers . A statistically significant difference was observed in the level of chromosomal aberrations in somatic cells from alcoholics when compared with controls ( 3.01 % vs. 1.28 % , p < or = 0.001 ) . A follow-up study was carried out for a subset of the patients after 3 months ( 8 subjects ) and 12 months ( 14 subjects ) of controlled abstinence . A statistically significant increase in the mean frequency of cells with aberrations was observed in the group of 14 subjects reinvestigated after 12 months of abstinence when compared with the mean value of the first blood sample s immediately after hospitalization ( 4.61 % vs. 3.01 % ; p < or = 0.001 ) . An excessive increase in cigarette consumption during alcohol abstinence , reflected by a dramatic elevation of CO-hemoglobin levels , may , at least in part , account for this finding . In conclusion , chronic alcoholism leads to genotoxic effects that , instead of recovering after 1 year of alcohol abstinence , are even enhanced , most likely due to the " shift in addictive behavior . Objectives . We used admissions data from the New York State addiction treatment system to assess patient self-reported tobacco use and factors associated with tobacco use . Methods . We compared prevalence of tobacco use in the state addiction treatment system with that of a national sample of people receiving addiction treatment and with that of the New York general population in 2005 to 2008 . A r and om effects logistic model assessed relationships between patient- and program-level variables and tobacco use . Results . Prevalence of tobacco use in the New York treatment system was similar to that in national addiction treatment data and was 3 to 4 times higher than that in the general population . Co-occurring mental illness , opiate use , methadone treatment , and being a child of a substance-abusing parent were associated with higher rates of tobacco use . Conclusions . We call on federal leadership to build capacity to address tobacco use in addiction treatment , and we call on state leadership to implement tobacco-free grounds policies in addiction treatment systems Increased pain sensitivity and the development of opioid tolerance complicate the treatment of pain experiencedby opioid maintained pregnantwomenduring delivery and the perinatal period . The aim of the present study was to investigate differences in pain management of opioid maintained compared to nondependent pregnant women during delivery and the postpartum period . 40 deliveries of 37 opioid dependent women enrolled in a double-blind , double-dummy r and omized controlled trial ( RCT ) examining the safety and efficacy of methadone ( mean dose at the time of delivery = 63.89 mg ) and buprenorphine ( mean dose at the time of delivery = 14.05 mg ) during pregnancy were analyzed and participants were matched to a non-dependent comparison group of 80 pregnant women . Differences in pain management ( opioid and non-opioid analgesic medication ) during delivery and perinatal period were analyzed . Following cesarean delivery opioid maintained women received significantly less opioid analgesics ( day of delivery p = 0.038 ; day 1 : p = 0.02 ) , NSAIDs were administered more frequently to opioid dependent patients than to the comparison group during cesarean section and on the third day postpartum . Significantly higher nicotine consumption in the group of opioid dependentwomenhad a strong influence onthe retrieved results , and might be considered as an independent factor of altered pain experience . Differences in pain treatment became evident when comparing opioid maintained women to healthy controls . These differences might be based on psychosocial consequences of opioid addiction along with the lack of an interdisciplinary consensus on pain treatment protocol s for opioid dependent patients BACKGROUND A high smoking prevalence has been registered among alcoholics . It has been pointed out that alcoholic smokers may have a more severe course and greater severity of alcoholism . This study aims at comparing smoking and non-smoking alcoholics in terms of treatment outcomes and verifying the efficacy of topiramate and naltrexone to decrease the use of cigarettes among alcoholic smokers . METHODS The investigation was a double-blind , placebo-controlled , 12-week study carried out at the University of São Paulo , Brazil . The sample comprised 155 male alcohol-dependent out patients ( 52 non-smokers and 103 smokers ) , 18 - 60 years of age , with an International Classification of Diseases ( ICD-10 ) diagnosis of alcohol dependence . After a 1-week detoxification period , the patients r and omly received placebo , naltrexone ( 50mg/day ) or topiramate ( up to 300 mg/day ) . Only the alcoholic smokers who adhered to the treatment were evaluated with reference to the smoking reduction . RESULTS Cox regression analysis revealed that the smoking status among alcoholics increased the odds of relapse into drinking by 65 % , independently of the medications prescribed , using the intention-to-treat method . Topiramate showed effectiveness to reduce the number of cigarettes smoked when compared to placebo among adherent patients ( mean difference=7.91 , p<0.01 ) . There were no significant differences between the naltrexone group and the placebo group . CONCLUSIONS The results of this study confirm that the treatment is more challenging for smoking alcoholics than for non-smoking ones and support the efficacy of topiramate in the smoking reduction among male alcoholic smokers who adhered to the treatment Cigarette smoking prevalence is very high , and cessation rates are very low , among people in methadone treatment . This may in part be due to interactions between methadone administration and cigarette smoking . The present study explores relationships between methadone dose timing and smoking rates . Twenty methadone patients , over a period of 19 days , used electronic cigarette packs to record their smoking patterns and called a voice mailbox daily to report their methadone dose and timing . The average proportion of daily cigarettes smoked was calculated for 2-hr blocks preceding and following methadone dose administration . For all participants , peak smoking rates occurred after methadone administration . Participants smoked a greater proportion of cigarettes in their first 2-hr block after methadone dosing ( M = 0.368 , SD = 0.135 ) than during their first 2-hr block of smoking of the day ( M = 0.245 , SD = 0.010 ; S = 85.5 , p < .0001 ) . The proportion of cigarettes smoked increased by 0.02 from more than 2 hr before methadone to the 2-hr time block before methadone , by 0.04 from the 2-hr time block before methadone to the 2-hr time block after methadone , and by 0.015 from the 2-hr time block after methadone to the next 2-hr time block . From this time block ( 2 - 4 hr after methadone ) , smoking decreased by 0.02 in the 4-plus hr postmethadone dose . All of these changes were statistically significant . Future research should use experimental design s to better examine whether a causal relationship exists and examine the impact of other types of opioid maintenance medications on smoking patterns Heroin dependence ( HD ) is a chronic relapsing brain disorder characterized by a compulsion to seek and use heroin . Stress is seen as a key factor for heroin use . Methadone maintenance and the prescription of pharmaceutical heroin [ diacetylmorphine ( DAM ) ] are established treatments for HD in several countries . The present study examined whether DAM‐maintained patients and methadone‐maintained patients differ from healthy controls in startle reflex and cortisol levels . Fifty‐seven participants , 19 of each group matched for age , sex and smoking status , completed a startle session which included the presentation of 24 bursts of white noise while eye‐blink responses to startling noises were recorded . Salivary cortisol was collected three times after awakening , before , during and after the startle session . DAM was administered before the experiment , while methadone was administered afterwards . Both heroin‐dependent patient groups exhibited significantly smaller startle responses than healthy controls ( P < 0.05 ) . Whereas the cortisol levels after awakening did not differ across the three groups , the experimental cortisol levels were significantly lower in DAM‐maintained patients , who received their opioid before the experiment , than in methadone‐maintained patients and healthy controls ( P < 0.0001 ) . Opioid maintenance treatment for HD is associated with reduced startle responses . Acute DAM administration may suppress cortisol levels , and DAM maintenance treatment may represent an effective alternative to methadone in stress‐sensitive , heroin‐dependent patients |
13,507 | 29,855,345 | Quantitative data were promising in regards to residents ’ depression symptoms , functioning and social care related quality of life .
Conclusion It is feasible to deliver and evaluate LifeFul . | Background The protective , custodial , task-oriented care provided in residential aged care facilitates decreases health and wellbeing of residents .
The aim of the study was to conduct a feasibility study of LifeFul – a 12 month reablement program in residential aged care . | 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 Objective To assess the effectiveness of an activity programme in improving function , quality of life , and falls in older people in residential care . Design Cluster r and omised controlled trial with one year follow-up . Setting 41 low level dependency residential care homes in New Zeal and . Participants 682 people aged 65 years or over . Interventions 330 residents were offered a goal setting and individualised activities of daily living activity programme by a gerontology nurse , reinforced by usual healthcare assistants ; 352 residents received social visits . Main outcome measures Function ( late life function and disability instruments , elderly mobility scale , FICSIT-4 balance test , timed up and go test ) , quality of life ( life satisfaction index , EuroQol ) , and falls ( time to fall over 12 months ) . Secondary outcomes were depressive symptoms and hospital admissions . Results 473 ( 70 % ) participants completed the trial . The programme had no impact overall . However , in contrast to residents with impaired cognition ( no differences between intervention and control group ) , those with normal cognition in the intervention group may have maintained overall function ( late life function and disability instrument total function , P=0.024 ) and lower limb function ( late life function and disability instrument basic lower extremity , P=0.015 ) . In residents with cognitive impairment , the likelihood of depression increased in the intervention group . No other outcomes differed between groups . Conclusion A programme of functional rehabilitation had minimal impact for elderly people in residential care with normal cognition but was not beneficial for those with poor cognition . Trial registration Australian Clinical Trials Register ACTRN12605000667617 PURPOSE OF THE STUDY The purpose of this study was to test the impact of Function-Focused Care for the Cognitively Impaired Intervention on nursing home residents with dementia and the nursing assistants who care for them . DESIGN AND METHODS This was a cluster-r and omized controlled trial using repeated measures . A total of 103 cognitively impaired residents and 77 nursing assistants were recruited from four nursing homes . For residents , outcome measures included function , physical activity ( survey and actigraphy ) , mood , behavior , and adverse events ( falls and hospitalization ) . Main outcome measures for nursing assistants included knowledge , beliefs , and performance of function focused care . RESULTS There were significant improvements in the amount and intensity of physical activity ( by survey and actigraphy ) and physical function in the treatment group . In addition , there was a significant decrease in the number of residents who fell during the treatment period with those in the treatment sites having fewer falls ( 28 % vs. 50 % in the control group ) . Nursing assistants were also observed to be providing a greater percentage of function focused care during resident care interactions in the treatment group at 6 months following the completion of baseline measures . IMPLICATION S This study provides some evidence that nursing home residents with severe cognitive impairment can safely and successfully be engaged in physical and functional activities Background There has been an increasing interest in reablement in Norway recently and many municipalities have implemented this form of rehabilitation despite a lack of robust evidence of its effectiveness . The aim of this study was to investigate the effectiveness of reablement in home-dwelling older adults compared with usual care in relation to daily activities , physical functioning , and health-related quality of life . Methods This is a parallel-group r and omised controlled trial conducted in a rural municipality in Norway . Sixty-one home-dwelling older adults with functional decline were r and omised to an intervention group ( n = 31 ) or a control group ( n = 30 ) . The intervention group received ten weeks of multicomponent home-based rehabilitation . The Canadian Occupational Performance Measure ( COPM ) was used to measure self-perceived activity performance and satisfaction with performance . In addition , physical capacity and health-related quality of life were measured . The participants were assessed at baseline and at 3- and 9-month follow-ups . Results There were significant improvements in mean scores favouring reablement in COPM performance at 3 months with a score of 1.5 points ( p = 0.02 ) , at 9 months 1.4 points ( p = 0.03 ) and overall treatment 1.5 points ( p = 0.01 ) , and for COPM satisfaction at 9 months 1.4 points ( p = 0.03 ) and overall treatment 1.2 points ( p = 0.04 ) . No significant group differences were found concerning COPM satisfaction at 3 months , physical capacity or health-related quality of life . Conclusion A 10-week reablement program result ed in better activity performance and satisfaction with performance on a long-term basis , but not the other outcomes measured . Trial registration The trial was registered in Clinical Trials.gov November 20 , 2012 , identifier NCT02043262 BACKGROUND frail older people often require tailored rehabilitation in order to remain at home , especially following a period of hospitalisation . Restorative care services aim to enhance an older person 's ability to remain improve physical functioning , either at home or in residential care but evidence of their effectiveness is limited . OBJECTIVE to evaluate the effectiveness of a restorative care service on institutional-free survival and health outcomes in frail older people referred for needs assessment in New Zeal and . METHODS a r and omised controlled trial of restorative care or usual care in 105 older people at risk of permanent residential who were follow-up over 24 months . The restorative care service was delivered in short-stay residential care facilities and at participants ' residences with the aim of reducing the requirement for permanent residential care . It included a comprehensive geriatric assessment and care plan developed and delivered , initially by a multi-disciplinary team and subsequently by home care assistants . RESULTS compared with usual care , there was a non-significant absolute risk reduction of 14.3 % for death or permanent residential care ( 8.8 % for residential care and 7.2 % for death alone ) for the restorative care approach . There was no difference in levels of burden among caregivers . CONCLUSIONS restorative care models that utilise case management and multi-disciplinary care may positively impact on institutional-free survival for frail older people without adversely impacting on the health of caregivers INTRODUCTION Health services delivered in an older person 's home are often implemented at a critical juncture in an individual 's functional status . Although homecare has potential to improve this situation , it often focuses on treating disease and ' taking care ' of the patient rather than promoting independence . The aim of restorative homecare is to change the philosophy from one where delivery of care may create dependency to provision of care which maximises independence , self-esteem , self-image and quality of life , and reduces the care required . AIMS To assess impact of a design ated goal facilitation tool on health-related quality of life ( HRQoL ) , social support and physical function among community-dwelling older people referred for homecare . METHODS A total of 205 participants [ mean age 79.1 years , 71.3 % female ( intervention group ) and 76.9 years with 60.8 % female ( control group ) ] were cluster r and omised to an intervention or control assessor . The intervention arm involved participants completing a goal facilitation tool with assessors . This established rehabilitation aims . Control participants received a st and ard needs assessment . Clients from both groups were then referred to a homecare organisation for service delivery . RESULTS There was greater change over time in HRQoL [ measured by Short Form 36 Survey ( SF-36 ) ] in the intervention group ( P = 0.0001 ) . There was a marked variation across homecare providers in types of services provided ( P < 0.001 ) . Identification of a goal did not predict completion of a formalised review of participants ' needs by the homecare organisation . CONCLUSIONS Use of a goal facilitation tool in assessment of an older person 's needs on referral for homecare leads to significant improvements in HRQoL. This may be through a higher proportion of individualised activities tailored to a successful identification of the person 's goals . The findings contribute to greater underst and ing of factors necessary to implement improvements in homecare services for older people A r and omised controlled trial was conducted to test the effectiveness of the Home Independence Program ( HIP ) , a restorative home-care programme for older adults , in reducing the need for ongoing services . Between June 2005 and August 2007 , 750 older adults referred to a home-care service for assistance with their personal care participated in the study and received HIP or ' usual ' home-care services . Service outcomes were compared at 3 and 12 months . Subgroups of 150 from each group were also compared on functional and quality of life measures . Data were analysed by ' intention-to-treat ' and ' as-treated ' . The intention-to-treat analysis showed at 3 and 12 months that the HIP group was significantly less likely to need ongoing personal care [ Odds ratio ( OR ) = 0.18 , 95 % CI = 0.13 - 0.26 , P < 0.001 ; OR = 0.22 , 95 % CI = 0.15 - 0.32 , P < 0.001 ] . Both subgroups showed improvements on the individual outcome measures over time with the only significant differences being found at 12 months for Instrumental Activities of Daily Living ( IADL ) in the as-treated analysis . Contamination of the control group by an increased emphasis on independence across the home-care agency involved , together with other method ological problems encountered , is thought to account for the few differences between groups in individual outcomes . Despite no difference between the groups over time in their overall ADL scores , a significantly smaller proportion of the HIP group required assistance with bathing/showering , the most common reason for referral , at 3 and 12 months . The results support earlier findings that participating in a short-term restorative programme appears to reduce the need for ongoing home care . The implementation of such programmes more broadly throughout Australia could substantially offset the projected increase in dem and for home care associated with the five-fold projected increase in numbers of the oldest old expected over the next 40 years Due to the ageing population , there is an increased dem and for home care services . Restorative care is one approach to improving home care services , although there is little evidence to support its use in the community setting . The objective of this trial was to evaluate the impact of a restorative home care service for community-dwelling older people . The study was a cluster r and omised controlled trial undertaken at a home care agency in New Zeal and . The study period was from December 2005 to May 2007 . Older people were interviewed face-to-face at baseline , four and 7 months . A total of 186 older people who received assistance from a home care agency participated in the study , 93 received restorative home care and 93 older people received usual home care . The primary outcome measure was change in health-related quality of life ( measured by the Short Form 36 [ SF36 ] Health Survey ) . Secondary outcomes were the physical , mental , and social well-being of older people ( Nottingham Extended Activities of Daily Living , Timed Up and Go , Mastery scale , Duke Social Support Index ) . Findings revealed that compared with usual care , the intervention demonstrated a statistically significant benefit in health-related quality of life ( SF36 ) at 7 months for older people ( mean difference 3.8 , 95 % CI -0.0 to 7.7 , P = 0.05 ) . There were no changes in other scale measurements for older people in either group over time . There was a statistically significant difference in the number of older people in the intervention group identified for reduced hours or discharge ( 29 % ) compared with the control group ( 0 % ) ( P < 0.001 ) . In conclusion , a restorative home care service may be of benefit to older people , and improves home care service efficacy OBJECTIVE To determine the impact of a restorative model of home care on social support and physical function among community-dwelling older people . DESIGN Cluster-r and omized controlled trial . SETTING Home care in an urban area . PARTICIPANTS Participants ( N=205 ) were r and omly assigned to an intervention group ( n=108 ; mean age , 79.1y ; 71.3 % women ; 81.5 % New Zeal and European [ NZE ] ; 50.8 % residing in areas of the highest levels of social deprivation ) or a usual care group ( n=97 ; mean age , 76.9y ; 60.8 % women ; 73.2 % NZE ; 53.5 % in the highest levels of social deprivation ) . INTERVENTION Participants r and omly assigned to the intervention group completed a goal facilitation tool with a needs assessor to determine their needs and to establish the aims for the episode of care . Services were structured according to the principles of restorative home care ( independence focused with individually tailored activity programs ) . Usual care participants received a st and ard needs assessment that informed the delivery of home care services . MAIN OUTCOME MEASURES Short Physical Performance Battery ( SPPB ) , Dukes Social Support Index ( DSSI ) . RESULTS There was greater change over time in physical function ( measured by SPPB : F=8.30 , P=.003 ) but no associated increase in social support ( as determined by DSSI : F=2.58 , P=.09 ) . CONCLUSIONS Significant improvements in physical function were observed after a period of restorative home care services . The absence of an associated change in social support may have been the result of a combination of factors , including the threshold of physical function required for community ambulation , the low rate of allied health service provision , and the time required to reestablish social ties . The findings contribute to a greater underst and ing of factors necessary to refocus home-based services to emphasize improvements in physical function and independence PURPOSE The relationship between job satisfaction of nurse aides and intent to leave and actual turnover after 1 year is examined . DESIGN AND METHODS Data came from a r and om sample of 72 nursing homes from 5 states ( Colorado , Florida , Michigan , New York , and Oregon ) . From these nursing homes , we collected 1,779 surveys from nurse aides ( a response rate of 62 % ) . We used a job satisfaction instrument specifically developed for use with nurse aides , as well as previously vali date d measures of intent to leave and turnover . We used ordered logistic regression and logistic regression to examine the data . RESULTS High overall job satisfaction was associated with low scores on thinking about leaving , thinking about a job search , search ing for a job , and turnover . In examining the association between the job satisfaction subscales and intent to leave and turnover , we found that high Work Schedule subscale scores , high Training subscale scores , and high Rewards subscale scores were associated with low scores on thinking about leaving , thinking about a job search , search ing for a job , and turnover . High scores on the Quality of Care subscale were associated with low turnover after 1 year . IMPLICATION S These results are important in clearly showing the relationship between job satisfaction and intent to leave and turnover of nurse aides . Training , rewards , and workload are particularly important aspects of nurse aides ' jobs |
13,508 | 30,496,768 | HighlightsWe found significantly lower blood magnesium levels , either in plasma or serum , in ADHD children than those in controls .
The serum magnesium levels in ADHD children was significantly lower than those in controls .
Also , in situation of definite diagnosis based upon DSM system , the subgroup meta‐ analysis revealed similar result .Finally , we also found significantly lower hair magnesium levels in children diagnosed with ADHD than those in controls | & NA ; The pathophysiology of attention deficient hyperactivity disorder ( ADHD ) is still obscure .
Some studies have discussed that magnesium levels are lower in the serum and erythrocytes of children with ADHD .
However , these findings are controversial .
The aim of our study is to identify whether magnesium levels are in fact lower in children with ADHD . | OBJECTIVE Adequate Zn and Mg intakes may be beneficial for the prevention and treatment of mental health problems , such as depression , anxiety and attention-deficit hyperactivity disorder . We aim ed to investigate the prospect i ve association between dietary intakes of Zn and Mg and internalising and externalising behaviour problems in a population -based cohort of adolescents . DESIGN Prospect i ve analysis ( general linear mixed models ) of dietary intakes of Zn and Mg assessed using a vali date d FFQ and mental health symptoms assessed using the Youth Self-Report ( YSR ) , adjusting for sex , physical activity , family income , supplement status , dietary misreporting , BMI , family functioning and energy intake . SETTING Western Australian Pregnancy Cohort ( Raine ) Study . SUBJECTS Adolescents ( n 684 ) at the 14- and 17-year follow-ups . RESULTS Higher dietary intake of Mg ( per SD increase ) was significantly associated with reduced externalising behaviours ( β = -1.45 ; 95 % CI -2.40 , -0.50 ; P = 0.003 ) . There was a trend towards reduced externalising behaviours with higher Zn intake ( per SD increase ; β = -0.73 ; 95 % CI -1.57 , 0.10 ; P = 0.085 ) . CONCLUSIONS The study shows an association between higher dietary Mg intake and reduced externalising behaviour problems in adolescents . We observed a similar trend , although not statistically significant , for Zn intake . R and omised controlled trials are necessary to determine any benefit of micronutrient supplementation in the prevention and treatment of mental health problems in adolescents Background Polyunsaturated fatty acids are essential nutrients for humans . They are structural and functional components of cell membranes and pre-stages of the hormonally and immunologically active eicosanoids . Recent discoveries have shown that the long-chained omega-3 fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) also play an important role in the central nervous system . They are essential for normal brain functioning including attention and other neuropsychological skills . Material s and methods In our large observational study we monitored 810 children from 5 to 12 years of age referred for medical help and recommended for consuming polyunsaturated fatty acids ( PUFA ) in combination with zinc and magnesium by a physician over a period of at least 3 months . The food supplement ESPRICO ® ( further on referred to as the food supplement ) is developed on the basis of current nutritional science and containing a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc . Study objective was to evaluate the nutritional effects of the PUFA-zinc-magnesium combination on symptoms of attention deficit , impulsivity , and hyperactivity as well as on emotional problems and sleep related parameters . Assessment was performed by internationally st and ardised evaluation scales , i.e. SNAP-IV and SDQ . Tolerance ( adverse events ) and acceptance ( compliance ) of the dietary therapy were documented . Results After 12 weeks of consumption of a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc most subjects showed a considerable reduction in symptoms of attention deficit and hyperactivity/impulsivity assessed by SNAP-IV . Further , the assessment by SDQ revealed fewer emotional problems at the end of the study period compared to baseline and also sleeping disorders . Mainly problems to fall asleep , decreased during the 12 week nutritional therapy . Regarding safety , no serious adverse events occurred . A total of 16 adverse events with a possible causal relationship to the study medication were reported by 14 children ( 1.7 % ) and only 5.2 % of the children discontinued the study due to acceptance problems . Continuation of consumption of the food supplement was recommended by the paediatricians for 61.1 % of the children . Conclusion Our results suggest a beneficial effect of a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc consumption on attentional , behavioural , and emotional problems of children and adolescents . Thus , considering the behavioural benefit in combination with the low risk due to a good safety profile , the dietary supplementation with PUFA in combination with zinc and magnesium can be recommended Children with ADHD are ' a group at risk ' as far as their further emotional and social development and educational possibilities are concerned , and the consequences of the lack of an appropriate therapy appears to be serious . Some of these children do not respond to prevailing therapy methods . It is reported that dietetic factors can play a significant role in the etiology of ADHD syndrome , and magnesium deficiency can help in revealing hyperactivity in children . The aim of our work was to assess the influence of magnesium supplementation on hyperactivity in patients with ADHD . The examination comprised 50 hyperactive children , aged 7 - 12 years , who fulfilled DSM IV criteria for ADHD syndrome , with recognized deficiency of magnesium in the blood ( blood serum and red blood cells ) and in hair using atomic absorption spectroscopy . In the period of 6 months those examined regularly took magnesium preparations in a dose of about 200 mg/day . 30 of those examined with ADHD showed coexisting disorders specific to developmental age , and 20 of them showed disruptive behaviour . The control group consisted of 25 children with ADHD and magnesium deficiency , who were treated in a st and ard way , without magnesium preparations . 15 members of this group showed coexisting disorders specific for developmental age , and 10 members showed disruptive behaviour . Hyperactivity was assessed with the aid of psychometric scales : the Conners Rating Scale for Parents and Teachers , Wender 's Scale of Behavior and the Quotient of Development to Freedom from Distractibility . In the group of children given 6 months of magnesium supplementation , independently of other mental disorders coexisting with hyperactivity , an increase in magnesium contents in hair and a significant decrease of hyperactivity of those examined has been achieved , compared to their clinical state before supplementation and compared to the control group which had not been treated with magnesium Levels of calcium in plasma , red blood cells , and mononuclear blood cells , levels of calcium in plasma , and the plasma calcium-to-magnesium ratio were measured at baseline and after 3 weeks of each drug phase of a double-blind , placebo-controlled study of methylpheni date and dextroamphetamine in hyperactive boys . Levels of magnesium in plasma were significantly higher after 3 weeks of dextroamphetamine treatment , and the calcium-to-magnesium ratio was significantly lower after 3 weeks of either drug compared with the baseline or placebo condition . There was no change in magnesium levels in red blood cells or mononuclear blood cells . These measures were obtained 30 minutes before the morning dose and at 9 a.m. , 9:30 a.m. , 10:30 a.m. , 11:00 a.m. , and noon on the last day of each 3-week phase . Analysis of variance revealed a drug effect on plasma magnesium and on the calcium-to-magnesium ratio but no drug x time interaction . Although these changes were not correlated with the time course of acute symptomatic response to stimulant therapy , the decrease in the ratio may be relevant to side effects and treatment resistance associated with stimulant use A positive influence of magnesium in the prevention and treatment of hyperactivity in children is more and more frequently raised in the literature . The aim of our work was to estimate magnesium contents in children with attention deficit hyperactivity disorder , ( ADHD ) . The investigations comprised 116 children ( 94 boys and 20 girls ) , aged 9 - 12 years , with recognized ADHD . In 68 out of 116 patients examined ADHD occurred with other coexisting disorders specific to the developmental age and in the remaining 48 patients it occurred together with disruptive behaviour . Magnesium levels have been determined in blood serum , red blood cells and in hair with the aid of atomic absorption spectroscopy . Magnesium deficiency was found in 95 per cent of those examined , most frequently in hair ( 77.6 per cent ) , in red blood cells ( 58.6 per cent ) and in blood serum ( 33.6 per cent ) of children with ADHD . The conclusion from the investigations is that magnesium deficiency in children with ADHD occurs more frequently than in healthy children . Analysis of the material indicated the correlation between levels of magnesium and the quotient of development to freedom from distractibility |
13,509 | 22,336,811 | AUTHORS ' CONCLUSIONS Available evidence nevertheless suggests that compared with st and ard care or no intervention , behavioral interventions are effective in reducing HIV and the incidence of STIs amongst female sex workers ( FSWs ) .
Given the benefits of social cognitive theory and the promotion of condom use in reducing HIV/STI and the public health need to control transmission amongst FSWs , there is a clear finding in favour of behavioral interventions . | BACKGROUND Various interventions have been adopted to reduce HIV transmission among sex workers and their clients but the effectiveness of these strategies has yet to be investigated using meta-analytic techniques .
OBJECTIVES To evaluate the effectiveness of behavioral interventions to reduce the transmission of HIV infection among sex workers and their clients in low- and middle-income countries . | The purpose of this study was to evaluate the effects of a brief intervention programme on STD knowledge , condom use and gonorrhoea incidence among sex workers in Singapore . A controlled before- and -after study design with non-r and om assignment of sex workers was used , supplemented by multivariate analysis to adjust for baseline differences . Control ( n = 221 , denoted C1 ) and experimental ( n = 221 , denoted E1 ) groups were interviewed on 2 occasions 3 months apart . Two supplementary groups were interviewed once each at the end of the 3-month period ( n = 145 who had received the intervention and n = 151 who had not ) . Basic knowledge of STD symptoms and HIV transmission was high in all groups . There were misconceptions about casual transmission of HIV which improved dramatically at the second interview for group El ( from 37–56 % correct responses to 82–90 % ) . Overall condom use was high ( about 75 % ) and did not change after the intervention . Gonorrhoea rates were correspondingly low ( 0.4 episodes/worker/year ) and also did not change . This brief intervention improved the STD knowledge of sex workers . However , behaviour as measured by reported condom use and gonorrhoea incidence did not change . Implication s for future intervention programmes are discussed Background Violence against female sex workers ( FSWs ) can impede HIV prevention efforts and contravenes their human rights . We developed a multi-layered violence intervention targeting policy makers , secondary stakeholders ( police , lawyers , media ) , and primary stakeholders ( FSWs ) , as part of wider HIV prevention programming involving > 60,000 FSWs in Karnataka state . This study examined if violence against FSWs is associated with reduced condom use and increased STI/HIV risk , and if addressing violence against FSWs within a large-scale HIV prevention program can reduce levels of violence against them . Methods FSWs were r and omly selected to participate in polling booth surveys ( PBS 2006 - 2008 ; short behavioural question naires administered anonymously ) and integrated behavioural-biological assessment s ( IBBAs 2005 - 2009 ; administered face-to-face ) . Results 3,852 FSWs participated in the IBBAs and 7,638 FSWs participated in the PBS . Overall , 11.0 % of FSWs in the IBBAs and 26.4 % of FSWs in the PBS reported being beaten or raped in the past year . FSWs who reported violence in the past year were significantly less likely to report condom use with clients ( zero unprotected sex acts in previous month , 55.4 % vs. 75.5 % , adjusted odds ratio ( AOR ) 0.4 , 95 % confidence interval ( CI ) 0.3 to 0.5 , p < 0.001 ) ; to have accessed the HIV intervention program ( ever contacted by peer educator , 84.9 % vs. 89.6 % , AOR 0.7 , 95 % CI 0.4 to 1.0 , p = 0.04 ) ; or to have ever visited the project sexual health clinic ( 59.0 % vs. 68.1 % , AOR 0.7 , 95 % CI 0.6 to 1.0 , p = 0.02 ) ; and were significantly more likely to be infected with gonorrhea ( 5.0 % vs. 2.6 % , AOR 1.9 , 95 % CI 1.1 to 3.3 , p = 0.02 ) . By the follow-up surveys , significant reductions were seen in the proportions of FSWs reporting violence compared with baseline ( IBBA 13.0 % vs. 9.0 % , AOR 0.7 , 95 % CI 0.5 to 0.9 p = 0.01 ; PBS 27.3 % vs. 18.9 % , crude OR 0.5 , 95 % CI 0.4 to 0.5 , p < 0.001 ) . Conclusions This program demonstrates that a structural approach to addressing violence can be effectively delivered at scale . Addressing violence against FSWs is important for the success of HIV prevention programs , and for protecting their basic human rights Background : In preparation for a r and omized controlled trial ( RCT ) , we conducted a pilot RCT of the acceptability and feasibility of diaphragms and c and i date vaginal microbicide for sexually transmitted infection prevention among high-risk women in Madagascar . Methods : Participants were r and omized to four arms : ( 1 ) diaphragm ( worn continuously ) with Acidform ™ applied in the dome ; ( 2 ) diaphragm ( worn continuously ) with placebo gel hydroxyethylcellulose ( HEC ) in the dome ; ( 3 ) HEC applied intravaginally before sex ; ( 4 ) Acidform applied intravaginally before sex . All women were given condoms . Participants were followed weekly for 4 weeks . We fit unadjusted negative binomial regression models with robust variance estimators to generate the proportion of sex acts with casual partners where condoms and experimental study products were used . Results : Retention was 98 % among 192 participants . Experimental product use with casual partners was high , reported in 85 % , 91 % , 74 % , and 81 % of sex acts for women in the Acidform-diaphragm , HEC-diaphragm , HEC-alone , and Acidform-alone arms , respectively . However , the proportion reporting product use during 100 % of acts with casual partners over the full follow-up period was much lower : 28 % to 29 % in the gel-diaphragm arms and 6 % to 10 % in gel-alone arms . Women used condoms in 62 % to 67 % of sex acts with casual partners , depending on the r and omization arm . Participants found diaphragms easy to insert ( 97 % ) and remove ( 96 % ) . Acidform users ( with or without the diaphragm ) reported more genitourinary symptoms than HEC users ( 14 % vs. 5 % of visits ) . Conclusions : A sexually transmitted infection prevention RCT of c and i date microbicide with and without the diaphragm appears acceptable and feasible in this population Objectives : To investigate changes in HIV-related behaviours among female sex workers ( FSW ) and associations with services coverage rates . Methods : Behavioural surveillance data from Sichuan , China , were analysed . A mapping exercise was conducted ; FSW were recruited from r and omly selected sex-work establishments in 19 sites in Sichuan , China , from 2003 ( n = 7068 ) , 2004 ( n = 6875 ) and 2005 ( n = 6833 ) . Results : Site variations were substantial . The r and om effect pooled AOR comparing the prevalence of condom use with regular sex partners , possession of condoms , HIV-related knowledge , HIV antibody testing and services coverage rates in 2005 versus 2003 ranged from 1.42 to 20.35 . The 95 % CI of these pooled AOR all excluded 1.0 ; hence rejecting the null hypothesis that such OR were not different from 1.0 . Most of the AOR of these evaluative parameters ( indicator of improvement ) for the 19 individual sites in 2004 and 2005 ( vs 2003 ) were significantly associated with coverage rates ( Spearmen correlation coefficients = 0.35 to 0.67 , p<0.05 ) . Conclusions : Improvements were observed in relevant behaviours and coverage rates and the two were associated with each other Objectives To examine the impact of a large-scale HIV prevention programme for female sex workers ( FSW ) in Karnataka state , south India , on the prevalence of HIV/sexually transmitted infections ( STI ) , condom use and programme coverage . Methods Baseline and follow-up integrated biological and behavioural surveys were conducted on r and om sample s of FSW in five districts in Karnataka between 2004 and 2009 . Results 4712 FSW participated in the study ( baseline 2312 ; follow-up 2400 ) , with follow-up surveys conducted 28–37 months after baseline . By follow-up , over 85 % of FSW reported contact by a peer educator and having visited a project STI clinic . Compared with baseline , there were reductions in the prevalence of HIV ( 19.6 % vs 16.4 % , adjusted odds ratio ( AOR ) 0.81 , 95 % CI 0.67 to 0.99 , p=0.04 ) ; high-titre syphilis ( 5.9 % vs 3.4 % , AOR 0.53 , 95 % CI 0.37 to 0.77 , p=0.001 ) ; and chlamydia and /or gonorrhoea ( 8.9 % vs 7.0 % , AOR 0.72 , 95 % CI 0.54 to 0.94 , p=0.02 ) . Reported condom use at last sex increased significantly for repeat clients ( 66.1 % vs 84.1 % , AOR 1.98 , 95 % CI 1.58 to 2.48 , p<0.001 ) and marginally for occasional clients ( 82.9 % vs 88.0 % , AOR 1.22 , 95 % CI 0.89 to 1.66 , p=0.2 ) , but remained stable for regular partners ( 32 % ) . Compared with street and home-based FSW , brothel-based FSW were at highest risk of HIV and STI , despite high levels of reported condom use . Conclusions This large-scale HIV prevention programme for FSW achieved reductions in HIV and STI prevalence , high rates of condom use with clients and high rates of programme coverage . Improved strategies to increase condom use with regular partners and reduce the vulnerability of brothel-based FSW to HIV are required Objective : To evaluate the effectiveness of a clinician-delivered intervention , implemented during routine clinical care , in reducing unprotected sexual behavior of HIV-infected patients . Design : A prospect i ve clinical trial comparing the impact of a clinician-delivered intervention arm vs. a st and ard-of-care control arm on unprotected sexual behavior of HIV-infected patients . Setting : The 2 largest HIV clinics in Connecticut . Participants : A total of 497 HIV-infected patients , aged ≥18 years , receiving HIV clinical care . Intervention : HIV clinical care providers conducted brief client-centered interventions at each clinical encounter that were design ed to help HIV-infected patients reduce unprotected sexual behavior . Main Outcome Measures : Unprotected insertive and receptive vaginal and anal intercourse and unprotected insertive oral sex ; unprotected insertive and receptive vaginal and anal intercourse only . Results : HIV-infected patients who received the clinician-delivered intervention showed significantly reduced unprotected insertive and receptive vaginal and anal intercourse and insertive oral sex over a follow-up interval of 18 months ( P < 0.05 ) . These behaviors increased across the study interval for patients in the st and ard-of-care control arm ( P < 0.01 ) . For the measure of unprotected insertive and receptive vaginal and anal sex only , there was a trend toward a reduction in unprotected sex among intervention arm participants over time ( P < 0.09 ) , and a significant increase in unprotected sex in the st and ard-of-care control arm ( P < 0.01 ) . Conclusions : A clinician-delivered HIV prevention intervention targeting HIV-infected patients result ed in reductions in unprotected sex . Interventions of this kind should be integrated into routine HIV clinical care Background and Objective : The Sonagachi Project in Calcutta , India , organized sex workers to improve working conditions . Goal : To compare rates of sexually transmitted diseases between the Sonagachi Project and other areas in which only the National AIDS Control Organization ( NACO ) interventions were implemented . Study : A cross-sectional survey of r and omly selected female sex workers . Results : There was no difference in the prevalence of all STDs between the 2 areas ; both were lower than reported in other surveys in 1992 . Analysis using propensity scores also failed to demonstrate any difference . The number of preventive activities was similar in the Sonagachi and NACO-only areas but was more prevalent than in 1992 . Sex workers in the Sonagachi area had better treatment-seeking behavior and attitudes . Both the Sonagachi and NACO strategies have result ed in lower STD rates , but the Sonagachi Project also increased the proportion who had an optimistic attitude and increased prevention and treatment-seeking behavior Background India has an estimated 2.0 million to 3.1 million people living with HIV ; it has the highest number of HIV-positive people in Asia and ranks third in the world . The Frontiers Prevention Project ( FPP ) was implemented in 2002 to conduct targeted prevention intervention geared towards female sex workers ( FSW ) and men who have sex with men ( MSM ) in the state of And hra Pradesh ( AP ) . This paper reports the overall changes in behaviour and STI outcomes between 2003/4 and 2007 and also describes the changes attributed to the FPP . Methods The evaluation used two cross-sectional surveys among MSM and FSW at 24 sites in AP . Surveys were implemented using a similar methodology . Univariate analyses were conducted by comparing means : baseline vs. four-year follow-up and FPP vs. non-FPP . For both MSM and FSW , r and om and fixed-effects logit regression models at the site level were estimated for condom use with last partner , syphilis sero-positivity and HSV 2 sero-positivity . In addition , for FSW we estimated models for condom use with regular partner , and for MSM we estimated models for condom use with last female partner . Results Among MSM , fixed-effects analysis revealed that FPP was positively correlated with the probability of condom use with last female sexual partner and negatively correlated with the individual probability of sero-positivity to syphilis and HSV 2 . Among FSW , the FPP intervention was significantly correlated with increased condom use with regular partners and with lower probability of STI sero-positivity . Discussion Important changes in behaviours related to an increase in prevention activities translated to reductions in STI sero-prevalence in AP , India . In contrast with non-FPP sites , the FPP sites experienced an intense community approach as part of the FPP intervention , and the general increase in condom use and its effect on STI sero-prevalence reflected the efficacy of these intense prevention activities focused on key population s in AP The development of non-invasive tests for evidence of current or past infection offers new prospect s for carrying out population studies of sexually transmitted infection ( STI ) epidemiology , and for improved underst and ing of the behavioural and biological determinants of STI transmission . In turn this may guide screening , treatment , and behavioural interventions . The evidence base for many interventions is sparse and r and omised trials of interventions are in their early days . Increasingly , linked behavioural and biological outcomes will be required to measure effectiveness . Integrated efforts are needed at a national level to achieve greater coordination between STD , HIV , and contraception services , school education , and broader public education and programmes Background Absence of knowledge of pregnancy-related pelvic girdle pain ( PPGP ) has prompted the start of a large cohort study in the Netherl and s. The objective of this study was to investigate the prevalence and incidence of PPGP , to identify risk factors involved in the onset and to determine the prognosis of pregnancy-related pelvic girdle pain . Methods / design 7,526 pregnant women of the southeast of the Netherl and s participated in a prospect i ve cohort study . During a 2-year period , they were recruited by midwives and gynecologists at 14 weeks of pregnancy . Participants completed a question naire at baseline , at 30 weeks of pregnancy , at 2 weeks after delivery , at 6 months after delivery and at 1 year after delivery . The study uses extensive question naires with questions ranging from physical complaints , limitations in activities , restriction in participation , work situation , demographics , lifestyle , pregnancy-related factors and psychosocial factors . Discussion This large-scale prospect i ve cohort study will provide reliable insights in incidence , prevalence and factors related to etiology and prognosis of pregnancy-related pelvic girdle pain Objective : To investigate the impact on sexual behaviour and sexually transmitted infections ( STI ) of a comprehensive community-led intervention programme for reducing sexual risk among female sex workers ( FSW ) in Mysore , India . The key programme components were : community mobilization and peer-mediated outreach ; increasing access to and utilization of sexual health services ; and enhancing the enabling environment to support programme activities . Methods : Two cross-sectional surveys among r and om sample s of FSW were conducted 30 months apart , in 2004 and 2006 . Results : Of over 1000 women who sell sex in Mysore city , 429 participated in the survey at baseline and 425 at follow-up . The median age was 30 years , median duration in sex work 4 years , and the majority were street based ( 88 % ) . Striking increases in condom use were seen between baseline and follow-up surveys : condom use at last sex with occasional clients was 65 % versus 90 % , P < 0001 ; with repeat clients 53 % versus 66 % , P < 0.001 ; and with regular partners 7 % versus 30 % , P < 0.001 . STI prevalence declined from baseline to follow-up : syphilis 25 % versus 12 % , P < 0.001 ; trichomonas infection 33 % versus 14 % , P < 0.001 ; chlamydial infection 11 % versus 5 % , P = 0.001 ; gonorrhoea 5 % versus 2 % , P = 0.03 . HIV prevalence remained stable ( 26 % versus 24 % ) , and detuned assay testing suggested a decline in recent HIV infections . Conclusion : This comprehensive HIV preventive intervention empowering FSW has result ed in striking increases in reported condom use and a concomitant reduction in the prevalence of curable STI . This model should be replicated in similar urban setting s across India The purpose of this study was to determine the pattern of STDs among commercial sex workers ( CSWs ) in Ibadan , Nigeria . The subjects were 169 CSWs r and omly selected from 18 brothels , majority of who were examined and investigated in their rooms . Another 136 women without symptoms who visited the special treatment clinic , University College Hospital , Ibadan were selected as a normal control group . Vaginal c and idiasis was the most common STD diagnosed in both CSWs and the control group . The other STDs in their order of frequency were HIV infection 34.3 % , non-specific vaginosis 24.9 % , trichomoniasis 21.9 % and gonorrhoea and " genital ulcers " had an incidence of 16.6 % each . Other important conditions were tinea cruris 18.9 % , scabies 7.7 % genital warts 6.5 % and 4.1 % of them had syphilis sero-positivity . All the 13 CSWs that had scabies , the 4 ( 36.4 % ) with genital warts and the 19 ( 67.9 % ) with " genital ulcers " had HIV infection . While there was no significant difference between the CSWs with vaginal c and idiasis , gonorrhoea , trichomoniasis and the control group , the HIV positivity was significantly higher ( P < 0.001 ) in CSWs than in the control subjects . These findings suggest that women who exchange sexual services for money can no longer be ignored , and should therefore be identified and made to participate in STD prevention and control programmes BACKGROUND Prevalent herpes simplex virus type 2 ( HSV-2 ) infection increases human immunodeficiency virus acquisition . We hypothesized that HSV-2 infection might also predispose individuals to acquire other common sexually transmitted infections ( STIs ) . METHODS We studied the association between prevalent HSV-2 infection and STI incidence in a prospect i ve , r and omized trial of periodic STI therapy among Kenyan female sex workers . Participants were screened monthly for infection with Neisseria gonorrhoeae and Chlamydia trachomatis , and at least every 6 months for bacterial vaginosis ( BV ) and infection with Treponema pallidum , Trichomonas vaginalis , and /or HSV-2 . RESULTS Increased prevalence of HSV-2 infection and increased prevalence of BV were each associated with the other ; the direction of causality could not be determined . After stratifying for sexual risk-taking , BV status , and antibiotic use , prevalent HSV-2 infection remained associated with an increased incidence of infection with N. gonorrhoeae ( incidence rate ratio [ IRR ] , 4.3 [ 95 % confidence interval { CI } , 1.5 - 12.2 ] ) , T. vaginalis ( IRR , 2.3 [ 95 % CI , 1.3 - 4.2 ] ) , and syphilis ( IRR , 4.7 [ 95 % CI , 1.1 - 19.9 ] ) . BV was associated with increased rates of infection with C. trachomatis ( IRR , 2.1 [ 95 % CI , 1.1 - 3.8 ] ) and T. vaginalis ( IRR , 8.0 [ 95 % CI , 3.2 - 19.8 ] ) . CONCLUSION ; Increased prevalences of HSV-2 infection and BV were associated with each other and also associated with enhanced susceptibility to an overlapping spectrum of other STIs . Demonstration of causality will require clinical trials that suppress HSV-2 infection , BV , or both Objective : Reporting bias due to social desirability is an important consideration in carrying out surveys on sensitive issues . The study compared the frequency of self reported sensitive behaviours and response rates between the conventional “ telephone interviewer method ” ( TIM ) and a combined interviewer and computerised data capturing method ( telephone interviewer and computerised question naire method , or TICQM ) . Methods : A total of 580 males and 582 females were recruited and r and omly assigned to either of the two methods in a cross sectional study . The overall response rate was about 51.6 % . Results : While the two methods both had high completion and low item non-response rates , the TICQM respondents reported higher frequencies of sensitive risk behaviours . Sexually active female respondents interviewed by the TICQM were more likely to report that their sex partners were their steady boyfriend , instead of their husb and ; and were also more likely to admit that they had had “ one night st and ” experiences or had undergone an HIV antibody test , when compared with their counterparts in the TIM group . Similar contrasts were observed for sexually active male respondents , that the TICQM group were more likely to report that they had had sexual intercourse with female sex workers or non-regular sex partners . Sex differences in the strength of association were observed between some studied behaviours ( for example , HIV testing and substance abuse ) and modes of data collection . Conclusion : The choice of data collection method has a significant impact on the results of sensitive studies ; special attention should be given to design ing the study and interpreting the results BACKGROUND Nonoxynol-9 ( rINN , nonoxinol-9 ) is an over-the-counter spermicide that has in-vitro anti-HIV-1 activity . Results of studies of its effectiveness in prevention of HIV-1 infection in women have been inconclusive . We aim ed to assess effectiveness of this vaginal gel . METHODS We did a r and omised , placebo-controlled , triple-blinded , phase 2/3 trial with COL-1492 , a nonoxynol-9 vaginal gel , in 892 female sex workers in four countries : Benin , Côte d'Ivoire , South Africa , and Thail and . 449 women were r and omly allocated nonoxynol-9 and 443 placebo . Primary endpoint was incident HIV-1 infection . Secondary endpoints included Neisseria gonorrhoeae and Chlamydia trachomatis infections . Analysis was by intention to treat . FINDINGS 765 women were included in the primary analysis . HIV-1 frequency in nonoxynol-9 users was 59 ( 16 % ) of 376 compared with 45 ( 12 % ) [ corrected ] of 389 in placebo users ( 402.5 vs 435.0 woman-years ; hazard ratio adjusted for centre 1.5 ; 95 % CI 1.0 - 2.2 ; p=0.047 ) . 239 ( 32 % ) women reported use of a mean of more than 3.5 applicators per working day , and in these women , risk of HIV-1 infection in nonoxynol-9 users was almost twice that in placebo users ( hazard ratio 1.8 ; 95 % CI 1.0 - 3.2 ) . 516 ( 68 % ) women used the gel less frequently than 3.5 times a day , and in these , risk did not differ between the two treatments . No significant effect of nonoxynol-9 on N gonorrhoeae ( 1.2 ; 0.9 - 1.6 ) or C trachomatis ( 1.2 ; 0.8 - 1.6 ) infections was reported . INTERPRETATION This study did not show a protective effect of COL-1492 on HIV-1 transmission in high-risk women . Multiple use of nonoxynol-9 could cause toxic effects enhancing HIV-1 infection . This drug can no longer be deemed a potential HIV-1-prevention method . Assessment of other microbicides should continue The Sonagachi Project was initiated in Kolkata , India in 1992 as a STD/HIV intervention for sex workers . The project evolved to adopt strategies common to women 's empowerment programs globally ( i.e. , community mobilization , rights-based framing , advocacy , micro-finance ) to address common factors that support effective , evidence -based HIV/STD prevention . The Sonagachi model is now a broadly diffused evidence -based empowerment program . We previously demonstrated significant condom use increases among female sex workers in a 16 month replication trial of the Sonagachi empowerment intervention ( n=110 ) compared to a control community ( n=106 ) receiving st and ard care of STD clinic , condom promotion , and peer education in two r and omly assigned rural towns in West Bengal , India ( Basu et al. , 2004 ) . This article examines the intervention 's impacts on 21 measured variables reflecting five common factors of effective HIV/STD prevention programs to estimate the impact of empowerment strategies on HIV/STD prevention program goals . The intervention which was conducted in 2000 - 2001 significantly : 1 ) improved knowledge of STDs and condom protection from STD and HIV , and maintained STD/HIV risk perceptions despite treatment ; 2 ) provided a frame to motivate change based on reframing sex work as valid work , increasing disclosure of profession , and instilling a hopeful future orientation reflected in desire for more education or training ; 3 ) improved skills in sexual and workplace negotiations reflected in increased refusal , condom decision-making , and ability to change work contract , but not ability to take leave ; 4 ) built social support by increasing social interactions outside work , social function participation , and helping other sex workers ; and 5 ) addressed environmental barriers of economic vulnerabilities by increasing savings and alternative income , but not working in other locations , nor reduced loan taking , and did not increase voting to build social capital . This study 's results demonstrate that , compared to narrowcast clinical and prevention services alone , empowerment strategies can significantly impact a broader range of factors to reduce vulnerability to HIV/STDs Summary : To test the efficacy of a sustainable community-level HIV intervention among sex workers , the Sonagachi Project was replicated , including community organizing and advocacy , peer education , condom social marketing , and establishment of a health clinic . Sex workers were r and omly selected in 2 small urban communities in northeastern India ( n = 100 each ) and assessed every 5–6 months over 15 months ( 85 % retention ) . Overall condom use increased significantly in the intervention community ( 39 % ) compared with the control community ( 11 % ) , and the proportion of consistent condom users increased 25 % in the intervention community compared with a 16 % decrease in the control community . This study supports the efficacy of the Sonagachi model intervention in increasing condom use and maintaining low HIV prevalence among sex workers Our objectives were to describe the baseline findings of a trial of antibiotic prophylaxis to prevent sexually transmitted infections ( STIs ) and HIV-1 in a cohort of Nairobi female sex workers ( FSWs ) . A question naire was administered and a medical examination was performed . HIV-negative women were r and omly assigned to either one gram azithromycin or placebo monthly . Mean age of the 318 women was 32 years , mean duration of sex work 7 years and mean number of clients was 4 per day . High-risk behaviour was frequent : 14 % practised anal intercourse , 23 % sex during menses , and 3 % used intravenous drugs . While 20 % reported condom use with all clients , 37 % never use condoms . However , STI prevalence was relatively low : HIV-1 27 % , bacterial vaginosis 46 % , Trichomonas vaginalis 13 % , Neisseria gonorrhoeae 8 % , Chlamydia trachomatis 7 % , syphilis 6 % and cervical intraepithelial neoplasia ( CIN ) 3 % . It appears feasible to access a population of high-risk FSWs in Nairobi with prevention programmes , including a proposed trial of HIV prevention through STI chemoprophylaxis Existing research indicates that sex workers who inject drugs are vulnerable to HIV infection through both risky sexual and drug use practice s. This study is the first attempt to learn whether this increased risk persists among current sex workers who participate in syringe exchange programmes ( SEPs ) . With data from interviews with r and omly selected participants in five US cities , we compared the demographic characteristics , sexual risk behaviours , drug use practice s , emotional and physical health , and SEP utilization patterns of currently active female sex workers who attend SEPs with female SEP participants who do not engage in sex work . Data indicate that women enrolled in SEPs who were currently trading sex typically reported greater HIV risk than women non-sex workers . Current sex workers reported higher levels of risk for every drug risk variable examined in bivariate analysis . They were more likely than other women to inject with a syringe previously used by someone else , to inject daily and to attend shooting galleries ; they were less likely to use a condom with their primary partners and to report higher levels of psychological distress than their counterparts . The relationship between sex work status and risky injection practice s persisted when potential confounders were controlled for in multivariate analysis . SEPs can serve a pivotal role in providing sex workers with services and referrals which would help them reduce risk behaviours 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 Objectives : To explore and evaluate a sexually transmitted disease (STD)/HIV intervention program targeting female sex workers working in entertainment establishments in five different setting s in China . Design and method : A prospect i ve , community-based , pre/post , intervention trial set in entertainment establishments ( karaoke bars , massage parlours , dance halls , beauty parlours ) where sex workers operate at sites in five provinces of China : Anhui , Beijing , Fujian , Guangxi and Xinjiang . The participants were all sex workers working in targeted entertainment establishments . A Women 's Health Clinic was set up near participants ' places of work at each site . Clinic-based outreach activities , including awareness-raising , condom promotion , and sexual health care , were developed and delivered to sex workers . Cross-sectional surveys at baseline and post-intervention were used to evaluate changes in condom use with the last three clients , and the prevalence of chlamydia and gonorrhoea . Results : In total , 907 sex workers were surveyed at baseline and 782 at 12 months post-intervention . Outreach teams made 2552 visits to the target entertainment establishments , approached 13 785 female sex workers , and distributed 33 575 copies of education material and 5102 packets of condoms . The rate of condom use with the most recent three clients increased from 55.2 % at baseline to 67.5 % at 12 months evaluation . The prevalence of gonorrhoea fell from 26 % at baseline to 4 % after intervention , and that of chlamydia fell from about 41 to 26 % . Conclusion : The intervention was effective for increasing condom use and reducing STD among sex workers . The results were used to develop national guidelines on sex worker interventions for nationwide scale up Objectives : To test the effect of supplementing peer promotion of male condom use with clinic based counselling , measured in terms of STI prevalence and reported male condom use . Methods : 1000 female sex workers in Madagascar were r and omised to two study arms : peer education supplemented by individual risk reduction counselling by a clinician ( peer + clinic ) versus condom promotion by peer educators only ( peer only ) . STI testing was conducted at baseline and 6 months . Behavioural interviews were administered at baseline , 2 , 4 , and 6 months . Results : At baseline , women in the peer only arm had prevalences of 16.0 % , 23.6 % , and 12.1 % for chlamydia , gonorrhoea , and trichomoniasis respectively , with an aggregate prevalence of 38.2 % . Baseline STI prevalences for the peer + clinic arm were slightly lower and 34.1 % in aggregate . At 6 months , aggregate STI prevalence increased in the peer only arm to 41.4 % , whereas the aggregate prevalence diminished slightly to 32.1 % in the peer + clinic arm . In logistic regression analyses , the estimated odds ratios ( ORs ) for chlamydia , gonorrhoea , trichomoniasis , and aggregate STI were 0.7 ( 95 % confidence interval 0.4 to 1.0 ) , 0.7 ( 0.5 to 1.0 ) , 0.8 ( 0.6 to 1.2 ) , and 0.7 ( 0.5 to 0.9 ) respectively , comparing the peer + clinic arm with the peer only arm . The logistic regression OR for reported condom use with clients in the past 30 days increased from 1.1 at 2 months to 1.8 at 6 months , comparing the peer + clinic arm with the peer only arm , and was 1.4 overall ( 1.1 to 1.8 ) . Adjustment for baseline factors changed the regression results little . Conclusions : The impact of male condom promotion on behaviour can be heightened through more concentrated counselling on risk reduction . Persistently high STI prevalence despite increases in reported condom use by sex workers supports the need for multidimensional control programmes 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 OBJECTIVE To describe the design , methods and baseline findings of a multi-level prevention intervention to increase consistent condom use among persons at public social sites in Kingston , Jamaica , who have new or concurrent sexual partnerships . METHODS A two-arm r and omized controlled trial ( RCT ) of 147 sites where persons meet new sex partners . Sites were identified by community informants as places where people meet new sexual partners , which include bars , street locations , bus stops , malls and others . Sites were sorted into 50 clusters based on geographic proximity and type of site and r and omized to receive a multi-level site-based intervention or not . Intervention components include on-site HIV testing , condom promotion and peer education . Effectiveness of the intervention will be measured by comparing the proportion of persons with new or multiple partners in the past year who report recent inconsistent condom use at intervention vs. control sites . RESULTS Baseline surveys were conducted at 66 intervention ( 711 men , 845 women ) and 65 control sites ( 654 men , 738 women ) . Characteristics of intervention and control sites as well as the characteristics of patrons at these sites were similar . The outcome variable was balanced with approximately 30 % of men and 25 % of women at intervention and control sites reporting a new partner or more than one partner in the past year and recent inconsistent condom use . CONCLUSIONS The baseline findings confirm that the population is an appropriate target group for HIV prevention and that r and omization will provide the means to estimate programme effectiveness Objective : Identify patterns and behaviors among direct and indirect female sex workers ( DFSWs and IDFSWs , respectively ) across Cambodia 's 5 major cities from 1997 to 2003 . Methods : Interviews with DFSWs and IDFSWs followed r and om selection from clusters in 5 cities . Individual characteristics and condom use with clients and other partners were assessed in univariate and multivariate analyses . Results : From 1997 to 2003 , consistent condom use with clients increased from 53 % to 96 % among DFSWs and from 30 % to 84 % among IDFSWs . DFSWs reported staying in their profession longer , had fewer clients per day , stayed longer in each brothel , were in increasingly larger brothels , and were tested more for HIV . For IDFSWs , there were significant changes : more reported practicing commercial sex and testing for HIV . In adjusted models , reported condom use with clients was significantly higher among DFSWs in later survey years ( odds ratio [ OR ] , 2.17 ) and who were never married ( OR , 1.69 ) , were in larger brothels ( OR , 1.02 ) , and charged more for sex ( OR , 1.27 ) , but lower for DFSWs with sweethearts ( OR , 0.68 ) and who reported abnormal vaginal discharge ( OR , 0.52 ) . For IDFSWs , in the adjusted models , reported condom use with clients was higher in later years ( OR , 1.77 ) and for those reporting abnormal vaginal discharge ( OR , 1.34 ) and HIV testing ( OR , 1.46 ) , and lower for those with sweethearts ( OR , 0.49 ) . Conclusions : From 1997 to 2003 , Cambodian direct and indirect sex workers increased their use of condoms each year with commercial as well as noncommercial partners , contributing to the evidence that HIV prevention programs can produce significant changes in risk behaviors OBJECTIVES We examined the efficacy of a brief behavioral intervention to promote condom use among female sex workers in Tijuana and Ciudad Juarez , Mexico . METHODS We r and omized 924 female sex workers 18 years or older without known HIV infection living in Tijuana and Ciudad Juarez who had recently had unprotected sex with clients to a 30-minute behavioral intervention or a didactic control condition . At baseline and 6 months , women underwent interviews and testing for HIV , syphilis , gonorrhea , and chlamydia . RESULTS We observed a 40 % decline in cumulative sexually transmitted illness incidence ( P = .049 ) in the intervention group . Incidence density for the intervention versus control groups was 13.8 versus 24.92 per 100 person-years for sexually transmitted illnesses combined ( P = .034 ) and 0 versus 2.01 per 100 person-years for HIV ( P < .001 ) . There were concomitant increases in the number and percentage of protected sex acts and decreases in the number of unprotected sex acts with clients ( P < .05 ) . CONCLUSIONS This brief behavioral intervention shows promise in reducing HIV and sexually transmitted illness risk behaviors among female sex workers and may be transferable to other re source -constrained setting This study evaluated the efficacy of an HIV intervention among female sex workers ( FSWs ) r and omized to an intervention or wait-list control . FSWs ( N = 120 ) completed baseline , 3- and 6-month assessment s. A health educator implemented 2-hour intervention emphasized gender-empowerment , self-efficacy to persuade clients to use condoms , condom application skills , and eroticizing safer sex . Over the 6-month follow-up , FSWs in the intervention reported more consistent condom use with clients ( P = .004 ) and were more likely to apply condoms on clients ( P = .0001 ) . Intervention effects were observed for other psychosocial mediators of safer sex . Brief , gender and culturally congruent interventions can enhance HIV-preventive behaviors among FSWs Abstract Mobile population s are vulnerable to contracting HIV . The present study aims to evaluate the relative efficacy of the voluntary counseling and testing plus information dissemination ( VCT-ID ) approach versus the information dissemination ( ID ) approach for promoting HIV preventive behaviors in a mobile population , cross-border truck drivers . A total of 301 adult male cross-border truck drivers who self-reported having had sex with female sex workers ( FSW ) or non-regular sex partners ( NRPs ) in mainl and China in the last 12 months were recruited and r and omized into the VCT-ID intervention group ( Group I ) or ID control group ( Group C ) . Anonymous structured question naires , administered through a computer-assisted method , were used to collect data . At the follow-up survey ( about 8–9 weeks since the baseline survey ) , Group I participants , as compared to Group C participants , were more likely to be consistent condom users when having sex with FSW ( 85.5 % versus 68.5 % , p<0.05 ) and with NRP ( 54.8 % versus 36.4 % , p<0.1 ) , more knowledgeable about HIV , and were less likely to have contracted sexually transmitted diseases ( STD ) in the last two months . The VCT-ID approach is shown to be more efficacious than the ID approach in promoting safer sex and HIV-related knowledge among local cross-border truck drivers . Feasibility of providing voluntary counseling and testing ( VCT ) services at locations which are convenient to the target population is demonstrated . It also shows that VCT services can be used as a means of HIV prevention . The findings of this study result ed in up-scaled VCT services for the local target population STUDY OBJECTIVE : To compare the association between different measures of condom use and prevalent HIV infection . DESIGN : R and omised cross sectional study to assess association between HIV infection and different measures of self reported condom use . Female sex workers were r and omised to one of five different face to face question naires on condom use . Three question naires used always to never scales to measure use but differed in the reference period for use ; a fourth asked about use in the last 10 coital acts ; and the fifth was a retrospective log of coital acts in the past two weeks . Use was assessed with new clients , repeat clients , and non-clients . SETTING : Yaoundé and Douala , Cameroon . PARTICIPANTS : 2266 female sex workers . MAIN RESULTS : The association between condom use and prevalent HIV infection varied for different measures of condom use . None of the five level measures showed a dose response protective effect of condom use . Measures aim ed at reducing recall bias ( measures based on the past 10 coital acts or a coital log ) showed little or no association with prevalent infection . Measures based on the past month or six months had a stronger association with prevalent infection . Regardless of the type of measure or reference period , the strongest association between use and infection was for use with partners who were not clients . CONCLUSION : These findings underscore challenges described by others of measuring condom use and interpreting the association between use and prevalent infection This article compares cross-sectional measures of condom use among 2,269 female sex workers in Cameroon r and omly assigned to receive one of five different question naires measuring condom use . We found that the level of reported condom use varied depending on the type of survey questions used . Measures based on 2-week coital logs or the past 10 acts categorized more women as " 100 % " or " 0 % " users than always-to-never scales categorized women as " always " or " never " users . Consistency of use also varied by type of partner . Internal consistency of responses was high . Future studies should assess differences in prospect i ve measures of condom use and the level of association between various measures and infection with sexually transmitted disease OBJECTIVES We sought to obtain evidence about the scope of women 's empowerment and the mechanisms underlying the significant reduction in intimate partner violence documented by the Intervention With Microfinance for AIDS and Gender Equity ( IMAGE ) cluster-r and omized trial in rural South Africa . METHODS The IMAGE intervention combined a microfinance program with participatory training on underst and ing HIV infection , gender norms , domestic violence , and sexuality . Outcome measures included past year 's experience of intimate partner violence and 9 indicators of women 's empowerment . Qualitative data about changes occurring within intimate relationships , loan groups , and the community were also collected . RESULTS After 2 years , the risk of past-year physical or sexual violence by an intimate partner was reduced by more than half ( adjusted risk ratio=0.45 ; 95 % confidence interval=0.23 , 0.91 ) . Improvements in all 9 indicators of empowerment were observed . Reductions in violence result ed from a range of responses enabling women to challenge the acceptability of violence , expect and receive better treatment from partners , leave abusive relationships , and raise public awareness about intimate partner violence . CONCLUSIONS Our findings , both qualitative and quantitative , indicate that economic and social empowerment of women can contribute to reductions in intimate partner violence Background : This study describes the extent to which commercial sex workers ( CSW ) in Cebu City , Philippines perceive prophylactic antibiotic use to be an effective form of prevention for sexually transmitted diseases ( STD ) and human immunodeficiency virus ( HIV ) , as well as the prevalence of this self‐treatment practice . Methods : A survey instrument was developed and pretested after 3 months of intensive ethnographic research on STD and acquired immune deficiency syndrome ( AIDS ) . A multistage sampling procedure was followed to ensure that a representative sample of CSW from four distinct work environments would be interviewed . Commercial sex workers registered at the Cebu City social hygiene clinic were sample d r and omly from coded work establishment lists , and a convenience sample of unregistered freelance CSW was secured . In total , 200 CSW were interviewed . Of these 200 CSW , all were sexually active , but only 160 had been engaged actively in commercial sexual exchange the month before their interviews . Results : Popular use of antibiotics as prophylaxis against STD is commonplace in the Philippines among CSW , with 38 % reporting routine or occasional use and 31 % reporting use in the last 2 weeks . Unregistered CSW are five times more likely to use prophylactic antibiotics than registered CSW , and they are seven times less likely to use condoms with 80 % or more of their customers . They also have sex with three times as many customers . Conclusions : Use of prophylactic antibiotics by CSW offers them a false sense of security in a high‐risk work environment . Self‐treatment with low‐dose prophylactic antibiotics provides no protection against STD , impedes STD screening efforts , and contributes to antibiotic resistance . An alarming percentage of CSW consider antibiotics a potential means of protecting themselves against AIDS . Public health interventions focusing on STD and AIDS in developing countries must address current patterns of prophylactic antibiotic use BACKGROUND In Latin America , motels rent rooms for commercial and non-commercial sex . We investigated the impact of providing health-education material and condoms on condom use in Managua , Nicaragua . METHODS In a r and omised controlled trial , in 19 motels , we gave condoms on request , made them available in rooms , or gave condoms directly to couples , with and without the presence of health-education material in the rooms . In a factorial design we assessed condom use directly by search ing the rooms after couples had left . FINDINGS 11 motels were used mainly by sex workers and their clients and eight mainly for non-commercial sex . 6463 couples attended the motels in 24 days . On 3106 ( 48.0 % ) occasions , at least one used condom was retrieved . Condom use was more frequent for commercial sex than for non-commercial sex ( 60.5 vs 20.2 % ) . The presence of health-education material lowered the frequency of condom use for commercial sex ( odds ratio 0.89 [ 95 % CI 0.84 - 0.94 ] ) and had no effect on use for non-commercial sex ( 1.03 [ 0.97 - 1.08 ] ) . Condom use increased for commercial ( 1.31 [ 1.09 - 1.75 ] ) and non-commercial sex ( 1.81 ( 1.14 - 2.81 ) if condoms were available in rooms . Directly h and ing condoms to couples was similarly effective for commercial sex but less effective for non-commercial sex ( 1.32 [ 1.03 - 1.61 ] vs 1.52 [ 1.01 - 2.38 ] ) . INTERPRETATION In Latin America , motels are key locations for promoting the use of condoms . Making condoms available in rooms is the most effective strategy to increase condom use , whereas use of health-education material was ineffective . These findings have important implication s for HIV-prevention policies Female sex workers have been central in India ’s HIV epidemic since it was first diagnosed among them in 1989 . Female sex workers ’ risk of HIV is primarily economically motivated . The Pi pilot study examined the feasibility and association of a microenterprise intervention , the tailoring of canvas bags , on sexual risk behaviors among female sex workers ( N = 100 ) in Chennai . Women were r and omized to an intervention or control arm . Between-group comparisons at baseline and at six-month follow-up were performed . Multivariate linear regression with bootstrapping was conducted to estimate the intervention effect . At baseline , women were a median of 35 years old , 61 % were married and they had an average of two children . Intervention participants reported a significantly lower number of sex partners and significant increases in income at the 6-month follow-up compared to control participants . In a multivariate model , intervention participants had a significantly lower number of paying clients per month at follow-up compared to control participants . By graduation , 75 % of intervention arm participants had made at least one sellable canvas bag and 6 months after the study ’s end , 60 % have continued involvement in bag production . The pilot study demonstrated that microenterprise interventions are successful in both providing FSWs with licit income opportunities and was associated with reductions in HIV risk behaviors Female sex workers are at high risk for infection with HIV , and their clients may act as a bridging population by spreading HIV to the general population . Comprehensive HIV surveillance among sex workers includes surveillance of HIV infection , of sexually transmitted infections and of risk behavior . Surveillance of HIV infection among sex workers is critical for countries with low-level or concentrated HIV epidemics , and can help in monitoring the response to the HIV epidemic in countries with a generalized epidemic . Sex workers are a vulnerable population , and particular attention needs to be paid to human rights issues including consent , confidentiality and stigma . Collaborations with key players in the local sex work scene -- sex workers themselves in the first place-- and alliances with salient institutions and groups are key to the success of surveillance among sex workers . Surveillance activities should have a strong link to interventions targeted at sex workers . Surveillance for HIV infection among sex workers can be institution- or community-based . Institutional setting s include screening programs for registered sex workers , of sexually transmitted diseases clinics , and re-education camps . Specific sources of bias need to be considered in different setting s , and must be measured -- through the collection of socio-demographic and behavioral data --to allow a correct interpretation of prevalence data and time trends . Community-based HIV infection surveillance can be conducted in a probability sample of the sex worker population , thereby reducing selection bias . This requires the mapping of sex workers ' contact venues , and drawing a r and om sample from the result ing sampling frame BACKGROUND Treatment of sexually-transmitted infections ( STIs ) and behavioural interventions are the main methods to prevent HIV in developing countries . We aim ed to assess the effect of these interventions on incidence of HIV-1 and other sexually-transmitted infections . METHODS We r and omly allocated all adults living in 18 communities in rural Ug and a to receive behavioural interventions alone ( group A ) , behavioural and STI interventions ( group B ) , or routine government health services and community development activities ( group C ) . The primary outcome was HIV-1 incidence . Secondary outcomes were incidence of herpes simplex virus type 2 ( HSV2 ) and active syphilis and prevalence of gonorrhoea , chlamydia , reported genital ulcers , reported genital discharge , and markers of behavioural change . Analysis was per protocol . FINDINGS Compared with group C , the incidence rate ratio of HIV-1 was 0.94 ( 0.60 - 1.45 , p=0.72 ) in group A and 1.00 ( 0.63 - 1.58 , p=0.98 ) in group B , and the prevalence ratio of use of condoms with last casual partner was 1.12 ( 95 % CI 0.99 - 1.25 ) in group A and 1.27 ( 1.02 - 1.56 ) in group B. Incidence of HSV2 was lower in group A than in group C ( incidence rate ratio 0.65 , 0.53 - 0.80 ) and incidence of active syphilis for high rapid plasma reagent test titre and prevalence of gonorrhoea were both lower in group B than in group C ( active syphilis incidence rate ratio , 0.52 , 0.27 - 0.98 ; gonorrhoea prevalence ratio , 0.25 , 0.10 - 0.64 ) . INTERPRETATION The interventions we used were insufficient to reduce HIV-1 incidence in rural Ug and a , where secular changes are occurring . More effective STI and behavioural interventions need to be developed for HIV control in mature epidemics BACKGROUND Prostitution is the most important source of transmission of AIDS and sexually transmitted diseases in Asia . We developed and evaluated the sustainability of an intervention to increase condom use and reduce gonorrhea among brothel-based sex workers in Singapore . The intervention focused on developing sex workers ' negotiation skills , educating clients , and mobilizing support from peers and health staff in promoting condom use . METHODS A pretest-posttest design with one intervention site ( n = 124 ) and another comparable control site ( n = 122 ) was maintained for 5 months followed by a time series design to follow up the intervention group for 2 years . RESULTS At 5 months , the intervention group improved significantly in negotiation skills and were almost twice as likely as controls to always refuse unprotected sex ( adjusted rate ratio 1.90 , 95 % CI 1.22 - 2.94 ) . Gonorrhea incidence declined considerably by 77.1 % in the intervention group compared with 37.6 % in the controls . Consistent refusals of unprotected sex in the intervention group increased from 44.4 % at baseline to 65.2 % at 5 months , 73.6 % at 1 year , and 90.5 % at 2 years with a corresponding decline in gonorrhea . CONCLUSION Sustained condom use with a corresponding decline in gonorrhea was achieved by a behavioral and environmental intervention for sex workers Objective : To examine the practice s of anal intercourse and dry sex within a cohort of female sex workers ( FSWs ) in Kenya , focusing on the prevalence and perceived risk of the practice s , demographic and behavioural correlates , and association with sexually transmitted infections ( STI ) . Methods : A survey was conducted among FSWs in Meru , Kenya , with 147 participants r and omly sample d from an existing cohort of self identified FSWs . Results : 40.8 % of participants reported ever practising anal intercourse and 36.1 % reported ever practising dry sex . Although the majority of women surveyed believed anal intercourse and dry sex to be high risk practice s for HIV infection compared with vaginal sex , about one third of women reported never or rarely using condoms during anal intercourse , and about 20 % never or rarely using condoms during dry sex . Reported consistent condom use was lower with both of these practice s than with penile-vaginal intercourse . Anal intercourse was associated with experience of recent forced sexual intercourse , while dry sex was not . Anal intercourse was almost always initiated by clients , whereas dry sex was likely to be initiated by the women themselves . Sex workers reported charging higher fees for both practice s than for vaginal intercourse . Both practice s were associated with reported symptoms and diagnoses of STI . Conclusions : Both anal intercourse and dry sex were common in this sample , and although perceived as high risk practice s , were not adequately protected with condom use . Education and other interventions regarding these high risk sexual behaviours need to be translated into safer practice s , particularly consistent condom use , even in the face of financial vulnerability This paper describes an HIV prevention intervention design ed in the US that was adapted and implemented in South Africa . Using an experimental design , 93 women who reported recent substance use and sex trading were r and omly assigned to a modified St and ard HIV intervention or to a Woman-Focused HIV prevention intervention . Eighty women completed the one-month follow-up interview . Participants reported high rates of sexual risk and violence at baseline . At follow-up , findings showed decreases in the proportion of women reporting unprotected sex and the daily use of alcohol and cocaine . Daily alcohol and cocaine use decreased more for women receiving the Woman-Focused intervention . Although violence continued to be a problem , at follow-up Woman-Focused participants reported being victimized less often than women receiving the St and ard intervention . This study demonstrates the feasibility of implementing cross-cultural behavioral HIV prevention interventions , and supports the need for future studies of women 's context ual issues and the effectiveness of targeted interventions CONTEXT Rates of HIV and AIDS have risen among U.S. Hispanics and in migrant-sending regions of Mexico and Central America , pointing to a link between migration and HIV . However , little is known about male migrants ' sexual risk behaviors , such as the use of commercial sex workers . METHODS The prevalence and frequency of commercial sex worker use was examined among 442 r and omly selected Hispanic migrants in Durham , North Carolina . Logistic and Poisson regression techniques were used to model predictors of commercial sex worker use , and descriptive data on condom use with commercial sex workers were examined . RESULTS Twenty-eight percent of respondents reported using the services of a commercial sex worker during the previous year ; rates reached 46 % among single men and 40 % among married men living apart from their wives . Men with spouses in Durham were less likely than other men to use commercial sex workers ( odds ratio , 0.1 ) . Among men who used commercial sex workers , the frequency of visits declined with greater education ( incidence rate ratio , 0.9 ) and increased with hourly wage ( 1.1 ) . Frequency and use declined with years of residence , although the results were of borderline significance . Reported rates of condom use with commercial sex workers were high , but were likely to fall if familiarity with a commercial sex worker increased . CONCLUSIONS Commercial sex workers represent an important potential source of HIV infection . Educational and behavioral interventions that take into account social context and target the most vulnerable migrants are needed to help migrants and their partners avoid HIV infection OBJECTIVE To develop and test an HIV intervention targeting sex workers and madams in the brothels of Bombay . SUBJECTS AND METHODS In a controlled intervention trial , with measurements before and after the intervention , 334 sex workers and 20 madams were recruited from an intervention site , and 207 and 17 , respectively , from a similar control site , both in red-light areas of Bombay . All sex workers were tested for antibodies to HIV and syphilis , and for hepatitis B surface antigen . Information on sexual practice s , condom use and knowledge of HIV was collected by interviewer-administered question naire . All subjects in the intervention group underwent a 6-month program of educational videos , small group discussion s and pictorial educational material s ; free condoms were also distributed . The blood tests and the question naire were readministered to all subjects at both sites immediately after the intervention . Both groups were followed for approximately 1 year . RESULTS The baseline level of knowledge about HIV and experience with condoms was extremely low among both sex workers and madams . The baseline prevalence of HIV antibodies was 47 % in the intervention group and 41 % in the control group ( P = 0.17 ) . The incidence densities for HIV and sexually transmitted diseases were significantly different in the two groups ( all P < 0.005 ) : 0.05 and 0.16 per person-year of follow-up for HIV , 0.08 and 0.22 per person-year for antibodies to syphilis , and 0.04 and 0.12 per person-year for hepatitis B surface antigen in the intervention and control women , respectively . Following the intervention , women reported increased levels of condom use , and some ( 41 % ) said they were willing to refuse clients who would n't use them . However , both the sex workers and the madams were concerned about losing business if condom use was insisted upon . CONCLUSIONS Both HIV prevalence and incidence are alarmingly high among female sex workers in Bombay . Successful interventions can be developed for these women , and even a partial increase in condom use may decrease the transmission of HIV and sexually transmitted diseases . Intervention programs of longer duration that target madams and clients and make condoms easily available are urgently needed at multiple sites in red-light areas Background : Linkages between sexual networks influence STD and HIV epidemics . Goal : This study quantifies male sexual “ bridging ” and associated factors in Cambodia 's 1997 behavioral surveillance survey . Study Design : Among persons r and omly selected from clusters of military , police , and motorcycle taxidrivers in five cities , associations between individual characteristics , behaviors , social context , and “ active bridging ” were tested using logistic regression analyses . Results : The authors defined 20.5 % , 15.7 % , and 14.7 % of military , police , and motorcycle taxidrivers as active bridgers ( men who have unprotected sex with high and low risk partners ) . Among the military and police , logistic regression revealed that age ( odds ratio [ OR ] , 1.05 ) , age of first sexual intercourse ( OR , 0.89 ) , having friends who frequent sex workers ( OR , 3.31 ) , and residence in the port city ( OR , 3.34 ) were associated with active bridging . Among motorcycle taxidrivers , residence in the border city ( OR , 2.23 ) or the port city ( OR , 2.84 ) was associated with active bridging . Sexually transmitted disease symptoms during the past year were significantly associated with active bridging . Conclusions : Social characteristics influence sexual bridging more than individual ones . The pervasiveness of bridging and the association with sexually transmitted disease symptoms underscore the potential of men who are active bridgers to spread sexually transmitted disease and HIV in Cambodia beyond high‐risk groups We investigated whether female condoms are acceptable to sex workers in Harare and whether improved access to male and female condoms increases the proportion of protected sex episodes with clients and boyfriends . Sex workers were r and omly placed in groups to receive either male and female condoms ( group A , n=99 ) or male condoms only ( group B , n=50 ) and were followed prospect ively for about 3 months each . We found a considerable burden of human immunodeficiency virus ( HIV ) and sexually transmitted infections ( STIs ) in our cohort at enrollment ( 86 % tested HIV positive and 34 % had at least one STI ) . Consistent male condom use with clients increased from 0 % to 52 % in group A and from 0 % to 82 % in group B between enrollment and first follow-up 2 weeks later and remained high throughout the study . Few women in group A reported using female condoms with clients consistently ( 3%–9 % ) , and use of either condom was less common with boyfriends than with clients throughout the study ( 8%–39 % ) for different study groups , visits , and types of condom ) . Unprotected sex still took place , as evidence d by an STI incidence of 16 episodes per 100 woman-months of follow-up . Our question naire data indicated high self-reported acceptability of female condoms , but focus group discussion s revealed that a main obstacle to female condom use was client distrust of unfamiliar methods . This study shows that a simple intervention of improving access to condoms can lead to more protected sex episodes between sex workers and clients . However , more work is needed to help sex workers achieve safer sex in noncommercial relationships Objectives : To assess whether individual clinic-based counselling as a supplement to peer education for male and female condom promotion leads to greater use of protection and lower STI prevalence among sex workers in Madagascar already exposed to intensive male condom promotion . Methods : In two public dispensaries in Madagascar , a total of 901 sex workers were r and omly allocated between two alternative male and female condom promotion interventions : peer education only , or peer education supplemented with individual clinic-based counselling . Participants were followed for 12 months . Every 2 months they made clinic visits , where they were interviewed on condom use . Peer educators counselled all participants on condom use as they accompanied their assigned participants to study visits . Participants assigned to receive the supplemental intervention were counselled by a trained clinician following study interviews . Participants were tested and treated for chlamydia , gonorrhoea and trichomoniasis every 6 months . We used logistic regression to assess whether the more intensive intervention was associated with reduced STI prevalence . Use of protection with clients and non-paying partners was assessed by study arm , site , and visit . Results : There was no statistically significant association between study arm and aggregated STI prevalence . No substantial differences in levels of reported protection were noted between study groups . Conclusions : This study found little evidence for gains from more thorough clinical counselling on male and female condom use . These findings suggest that less clinical ly intensive interventions such as peer education could be suitable for male and female condom promotion in population s already exposed to barrier method promotion Female sex workers are especially vulnerable to HIV infection , particularly those who use drugs and engage in street-based sex exchange . This study examines the risk behaviors and HIV serostatus of 806 drug-using female sex workers in Miami and assesses the relative impact of two HIV and hepatitis prevention interventions on changes in risk behavior . Drug-using sex workers were recruited using targeted sampling strategies and were r and omly assigned to the NIDA St and ard Intervention or an innovative Sex Worker Focused ( SWF ) Intervention . Outcome analyses indicate that both groups benefited from participation in the intervention trial . However , the SWF Intervention was found to be more efficacious in regard to reductions in unprotected oral sex and sexual violence Few studies have addressed recruitment and retention of participants in preventive interventions directed at human immunodeficiency virus ( HIV ) , and these generally have not focused on women . In this study , part of the Women in Group Support ( WINGS ) project , we examine the experience of three sites in recruiting 444 high-risk women for a small group intervention to reduce risky sexual behavior . The intervention included six structured sessions , followed by a continuing series of client-focused , drop-in sessions . Incentives for participants included child care , food , and transportation tokens . Attendees at each structured session also received a cash incentive of $ 10-$20 . Forty-six percent of the women were recruited from community sources , 35 % from clinics , and 19 % from drug programs . Across all recruitment sources , almost a third of the women reported having had a sexually transmitted disease ( STD ) in the past year , 88%-94 % reported a risky male partner ( who , they believed , had sex with other partners or with sex workers , was an injecting drug user , or was HIV positive ) , and 10%-36 % reported trading sex for money or drugs . During 18 months of recruitment , each site averaged 34 screening interviews monthly to secure 8 eligible women a month who completed baseline interviews and reported for r and omization . The average number of paid sessions attended by participants was five of six ( 83 % ) . Average attendance at unpaid sessions was 1 of 12 ( 8 % ) . Key facilitators to recruitment and retention included linkages with community agencies and monetary incentives . Our findings suggest that research ers and community service providers need to explore alternative strategies to paying women for attending group sessions ( e.g. , incorporating group interventions into existing program requirements ) and balance these against the costs and recruitment effectiveness CONTEXT Sexually transmitted infections ( STIs ) are common in female sex workers ( FSWs ) and may enhance susceptibility to infection with human immunodeficiency virus type 1 ( HIV-1 ) . OBJECTIVE To examine regular antibiotic prophylaxis in FSWs as a strategy for reducing the incidence of bacterial STIs and HIV-1 . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial conducted between 1998 - 2002 among FSWs in an urban slum area of Nairobi , Kenya . Of 890 FSWs screened , 466 who were seronegative for HIV-1 infection were enrolled and r and omly assigned to receive azithromycin ( n = 230 ) or placebo ( n = 236 ) . Groups were well matched at baseline for sexual risk taking and STI rates . INTERVENTION Monthly oral administration of 1 g of azithromycin or identical placebo , as directly observed therapy . All participants were provided with free condoms , risk-reduction counseling , and STI case management . MAIN OUTCOME MEASURES The primary study end point was incidence of HIV-1 infection . Secondary end points were the incidence of STIs due to Neisseria gonorrhoeae , Chlamydia trachomatis , Trichomonas vaginalis , Treponema pallidum , and Haemophilus ducreyi , as well as bacterial vaginosis . Analysis of herpes simplex virus type 2 ( HSV-2 ) infection was performed post hoc . RESULTS Seventy-three percent of participants ( n = 341 ) were followed up for 2 or more years or until they reached an administrative trial end point . Incidence of HIV-1 did not differ between treatment and placebo groups ( 4 % [ 19 cases per 473 person-years of follow-up ] vs 3.2 % [ 16 cases per 495 person-years of follow-up ] rate ratio [ RR ] , 1.2 ; 95 % CI , 0.6 - 2.5 ) . Incident HIV-1 infection was associated with preceding infection with N gonorrhoeae ( rate ratio [ RR ] , 4.9 ; 95 % CI , 1.7 - 14.3 ) or C trachomatis ( RR , 3.0 ; 95 % CI , 1.1 - 8.9 ) . There was a reduced incidence in the treatment group of infection with N gonorrhoeae ( RR , 0.46 ; 95 % CI , 0.31 - 0.68 ) , C trachomatis ( RR , 0.38 ; 95 % CI , 0.26 - 0.57 ) , and T vaginalis ( RR , 0.56 ; 95 % CI , 0.40 - 0.78 ) . The seroprevalence of HSV-2 infection at enrollment was 72.7 % , and HSV-2 infection at baseline was independently associated with HIV-1 acquisition ( RR , 6.3 ; 95 % CI , 1.5 - 27.1 ) . CONCLUSIONS Despite an association between bacterial STIs and acquisition of HIV-1 infection , the addition of monthly azithromycin prophylaxis to established HIV-1 risk reduction strategies substantially reduced the incidence of STIs but did not reduce the incidence of HIV-1 . Prevalent HSV-2 infection may have been an important cofactor in acquisition of HIV-1 The present study compared the results of behavioral surveillance data obtained on the male clients of female sex workers ( FSWs ) population in Hong Kong . Two surveys , using an identical method , were completed in 1998 and 2000 . Respectively , 1,020 and 2,074 respondents aged 18 - 60 who were r and omly selected from the general population participated in the study . About 12 % of the respondents had patronized FSWs in the past 6 months in 2000 as compared with 14 % in 1998 ( p = .143 ) . Crossing the border for sex and purchasing sex in multiple geographic areas was very common and a higher percentage of respondents reported having patronized FSWs in mainl and China in 2000 than in 1998 ( p = .003 ) . About 25 % of the respondents in both surveys had not always been using condoms ( i.e. , not used condoms every time ) when having sexual intercourse with FSWs . Those who practice d commercial sex in mainl and China were less likely to have always been using condoms with FSWs ( p < .01 ) and were more likely to have ever contracted STD in the past 6 months ( p < .05 ) , when compared with those who had purchased sex only in Hong Kong or in other places Background : The male condom is the most effective barrier method available for protection against sexually transmitted diseases ( STDs ) , including HIV infection . There is an urgent need to develop and evaluate other prevention methods , such as the female condom . This study estimated the additional protection against STDs offered to sex workers by giving them the option of using the female condom when clients refused to use a male condom . Methods : Sex establishments in four cities in Thail and were r and omized into two study groups : one in which sex workers were instructed to use male condoms consistently ( male condom group ) ; and one in which sex workers had the option of using the female condom if clients refused or were not able to use male condoms ( male/female condom group ) . R and omization was done by sex establishments , and not by individuals , to minimize sharing of female condoms across study groups . The proportion of unprotected sexual acts ( defined as sexual acts in which condoms were not used , tore , or slipped in or out ) and incidence rate of STDs ( gonorrhoea , chlamydial infection , trichomoniasis and genital ulcer disease ) were measured over a 24-week period and compared between the two study groups . Findings : Results are available from 34 sex establishments ( 249 women ) in the male/female condom group , and 37 sex establishments ( 255 women ) in the male condom group . Condom use was very high in both groups ( 97.9 and 97.3 % of all sexual acts , respectively , P > 0.05 ) . Male condom use was lower in the male/female condom group when compared with the male condom group ( 88.2 and 97.5 % , respectively , P < 0.001 ) . However , this reduction in male condom use was counterbalanced by the use of female condoms in 12.0 % of all sexual acts in the male/female condom group , contributing to a 17 % reduction in the proportion of unprotected sexual acts in this group when compared to the male condom group ( 5.9 versus 7.1 % , respectively , P = 0.16 ) . Female condom use was sustained over the entire study period . There was also a 24 % reduction in the weighted geometric mean incidence rate of STDs in the sex establishments of the male/female condom group compared to the male condom group ( 2.81 versus 3.69 per 100 person-weeks , P = 0.18 ) . Interpretation : The replacement of male condoms by female condoms in a proportion of sexual acts in the male/female condom group suggests that some sex workers and /or their clients preferred using the female condom . This switch in barrier method was accompanied by non-significant reductions in the proportion of unprotected sexual acts and in the incidence rate of STDs in the women of the male/female condom group . Special attention should be paid to a potential risk of slippage of the female condom in inexperienced users Research with injection drug users ( IDUs ) , at risk for acquiring and transmitting HIV , has focused primarily on their risky drug practice s , with far less attention paid to their risky sex behaviors . The purpose of this study was to determine what variables were associated with an increase in condom use following an HIV intervention with 3357 IDUs in nine cities . Participants reported using condoms during 15 % of their sexual encounters prior to the HIV intervention , and during 22 % of their sexual encounters six months later . A logistic regression analysis indicated that individuals who increased their condom use were likely to be HIV seropositive ( odds ratio OR = 2.49 ) , to have received AIDS information prior to the intervention ( OR = 1.28 ) , to have multiple sex partners ( OR = 2.14 ) , to be single with multiple sex partners ( OR = 1.34 ) , or to have exchanged drugs or money for sex ( OR = 1.33 ) . Discussion focuses on the generally low incidence of condom use and the need for increased intervention , particularly among drug users in monogamous relationships and sex workers Objective To compare the seroincidence of HIV infection among female sex workers in Abidjan , Côte d'Ivoire before and during an intervention study to control sexually transmitted diseases ( STD ) and to study the effect of two STD diagnosis and treatment strategies on the prevalence of STD and on the seroincidence of HIV infection . Method A screening facility for STD and HIV had been available since October 1992 for female sex workers . From June 1994 , women who were HIV seronegative or HIV-2 positive during the screening could enroll in the intervention study in which participants reported once a month to a confidential clinic where they received health education , condoms and STD treatment if indicated . Women in the study were r and omized either to a basic STD diagnosis and treatment strategy , which included a gynecologic examination when symptomatic , or to an intensive strategy that included a gynecologic examination regardless of symptoms . An outcome assessment every 6 months included a gynecologic examination , HIV serology and laboratory tests for STD . Results Of 542 women enrolled in the study , 225 ( 42 % ) had at least one outcome assessment . The HIV-1 seroincidence rate during the intervention study was significantly lower than before the study ( 6.5 versus 16.3 per 100 person-years;P = 0.02 ) . During the study , the HIV-1 seroincidence rate was slightly lower in the intensive than in the basic strategy ( 5.3 versus 7.6 per 100 person-years;P = 0.5 ) . Conclusion National AIDS control programs should consider adopting as policy the type of integrated approach used in this intervention study for HIV prevention in female sex workers ABSTRACT Purpose : The purpose of this study was to describe the coverage and portrayal of human immunodeficiency virus/acquired immune deficiency syndrome ( HIV/AIDS ) risk factors as framed in newspapers targeting Aboriginal ( First Nations , Métis , and Inuit ) peoples in Canada . Methods : From a sample of 31 Aboriginal newspapers published in English from 1996 to 2000 , 14 newspapers were r and omly selected . Of the 167 articles published on HIV/AIDS during this time period , all anecdotal ( n = 34 ) and an approximate 25 % r and om sample of scientific ( n = 32 ) articles were analyzed using both quantitative ( coding reliability and frequencies ) and qualitative ( in-depth content analysis ) analyses . Results : Individual risk factors for HIV/AIDS were described in 74 % ( 49/66 ) of the articles and included unprotected sexual intercourse ( 20/49 or 41 % ) , sharing of needles for injection drug use ( IDU ; 16/49 or 33 % ) , infected blood transfusions ( 3/49 or 6 % ) , and vertical transmission from mother to baby ( 10/49 or 20 % ) . Additional risk factors of alcohol use and poverty were mentioned in 29 % and 25 % of the articles . In addition to the well-recognized HIV/AIDS risk groups of prostitutes and homosexual men , sexual abuse victims , prisoners , and women were identified in Aboriginal newspapers as being at risk . Although Aboriginal women were identified as being at high risk , the newspaper coverage also emphasized their lack of knowledge regarding HIV/AIDS . Heterosexual men were not mentioned as being at risk for HIV/AIDS in the newspaper articles . Background : The prevalence of HIV/AIDS is higher among Canadian Aboriginals than in the general population . Local and community newspapers are an important channel for the dissemination of health information for isolated , rural , and Aboriginal communities . Interpretation : The findings show that Aboriginal media identify high-risk groups and individualistic risk factors for HIV/AIDS , within a public health perspective . The articles also emphasize , however , Aboriginal people 's lack of knowledge about disease transmission and the full spectrum of who is at risk Background and Objectives : Debate continues on the efficacy and safety of intravaginal nonoxynol‐9 for the prevention of horizontal transmission of human immunodeficiency and other sexually transmitted diseases . Little attention has been paid to the effects of nonoxynol‐9 contained in the lubricant of many condoms . Goal : To assess the tolerability of different levels of nonoxynol‐9 in condom lubricants . Study Design : Pilot , r and omized , controlled trial in 70 female prostitutes . Results : There was no association between dose of nonoxynol‐9 and reported symptoms or signs of genital tract inflammation ; an increased dose of nonoxynol‐9 was associated with increased numbers of polymorphonuclear leukocytes on a vaginal wall smear . Conclusions : There is no recognized simple method of defining inflammation in the female genital tract . Future studies of the effects of low‐dose nonoxynol‐9 on the female genital tract require highly controlled exposures , plus colposcopy with or without vaginal biopsy to define inflammation Background Low-dosenonoxynol-9 products have a potential advantage of reduced toxicity . However , little is known about their efficacy in reducing the incidence of sexuallytransmitted diseases(STDs ) . Goal Todetermine the effect that an intravaginal gel containing 52.5 mg ofnonoxynol-9 has on the acquisition of STDs in a cohort ofHIV-1–seronegative female sex workers in Mombasa , Kenya . Study Design A r and omized double-blind placebo controlled trialwasperformed . Results Inthis study , 139 women were r and omized to the nonoxynol-9 group and 139 to theplacebo group . No significant differences were found between the two study groups in terms of safety outcomes and reported symptoms , except for a lowerincidence of vaginal erythema in the nonoxynol-9 group . There was asignificantly higher incidence of gonorrhea in the nonoxynol-9 group than inthe placebo group . No significant differences were observed between the groupsfor acquisition of C and ida , trichomonas , bacterial vaginosis , Ctrachomatis , syphilis , or HIV-1 , although the statistical power todetect differences for some of these STDs waslimited . Conclusions Inthis r and omized placebo-controlled trial of a low-dose nonoxynol-9 gel , asignificantly higher incidence of gonorrhea was found in the nonoxynol-9group , but no significant differences between the groups were found for C and ida , trichomonas , bacterialvaginosis , C trachomatis , syphilis , orHIV-1 BACKGROUND Little is known about pregnancy rates among sex workers ( SWs ) or the factors that predispose SWs to this risk . We aim ed to estimate the pregnancy incidence rate among Madagascar SWs participating in an intervention trial promoting use of male and female condoms and assess the influence of various predictive factors on pregnancy risk . METHODS SWs from two study clinics in Madagascar participated in a r and omized trial to assess the effect of peer education and clinic-based counseling on use of male and female condoms and prevalence of sexually transmitted infections ( STIs ) . Women were seen every 2 months for up to 18 months ; they received structured interviews at every visit , and physical exams at baseline and every 6 months thereafter . Site staff recorded information on pregnancies during interviews ; pregnancy data were then merged with trial data for this analysis . RESULTS Of 935 SWs in the analysis population , 250 became pregnant during follow-up . The cumulative probability of pregnancy was 0.149 at 6 months and 0.227 at 12 months . Comparable proportions of nonpregnant and pregnant SWs reported using highly effective contraception at baseline ( approximately 16 % ) ; these users were younger and were more consistent condom users . Method switching and discontinuation were frequent . In multivariate analysis , nonuse of effective contraceptives and any self-reported unprotected sex were associated with higher incidence of pregnancy . Approximately 51 % of women delivered , 13 % reported a spontaneous abortion , 13 % reported an induced abortion and 23 % had missing pregnancy outcomes . CONCLUSIONS Women traditionally targeted for STI/HIV preventive interventions need more comprehensive reproductive health services . In particular , SWs could benefit from targeted family planning counseling and services There is an urgent need in sub-Saharan Africa to develop more effective methods of HIV prevention , including improved strategies of sexually transmitted infection ( STI ) prevention or an HIV vaccine . The efficacy of these strategies may be tested through clinical trials within cohorts at high risk for STI and HIV , such as female commercial sex workers . For ethical reasons , st and ard HIV prevention services , including access to free condoms , risk-reduction counseling , and STI therapy , will generally be offered to all study subjects . Because study subjects would often not otherwise have access to these prevention services , it is possible that enrollment in such clinical trials will itself reduce incidence rates of STI and HIV below expected levels , reducing the power to test the efficacy of the r and omized intervention . We show that the provision of st and ard HIV prevention services as part of a r and omized STI/HIV prevention trial is temporally associated with a dramatic reduction in sexual risk-taking , and that this reduction is directly associated with reduced STI incidence . This finding should be considered in the design of clinical trials with an endpoint of HIV incidence , in particular HIV preventive vaccine trials |
13,510 | 31,683,759 | We conclude that T2D is preventable by changing lifestyle and the risk reduction is sustained for many years after the active intervention ( high certainty of evidence ) .
There is limited or insufficient data to show that prevention of T2D by lifestyle changes results in a lower risk of cardiovascular and microvascular complications | Prevention of type 2 diabetes ( T2D ) is a great challenge worldwide .
The aim of this evidence synthesis was to summarize the available evidence in order to up date the European Association for the Study of Diabetes ( EASD ) clinical practice guidelines for nutrition therapy .
We conducted a systematic review and , where appropriate , meta-analyses of r and omized controlled trials ( RCTs ) carried out in people with impaired glucose tolerance ( IGT ) ( six studies ) or dysmetabolism ( one study ) to answer the following questions : What is the evidence that T2D is preventable by lifestyle changes ?
What is the optimal diet ( with a particular focus on diet quality ) for prevention , and does the prevention of T2D result in a lower risk of late complications of T2D ? | Background Prevalence of type 2 diabetes ( T2D ) is increasing worldwide . T2D prevention by lifestyle intervention is effective . Pragmatic scalable interventions are needed , with evidence to efficiently target and monitor such interventions . We report pooled analyses of data from three European trial cohorts : to analyse T2D incidence , sustained weight loss and utility of risk predictors . Methods We analysed data on 749 adults with impaired glucose tolerance ( 278 men and 471 women , mean age 56 years , mean BMI 31 kgm−2 ) recruited between 1993 and 2003 , and r and omised to intensive lifestyle intervention ( I ) or lifestyle advice control ( C ) . The intervention aim ed to increase physical activity , modify diet , and promote weight loss≥5 % . Using Cox-regression survival analysis , we assessed T2D incidence and the impact on T2D incidence of sustained weight loss , and of baseline cut-point values of FINDRISC score , fasting plasma glucose ( FPG ) , and HbA1c . Results Mean follow-up duration was 3.1 years . T2D was diagnosed in 139 participants ( I = 45/379 , C = 94/370 ) . Cumulative T2D incidence was 57 % lower in the intervention compared with the control group ( HR 0.42 ( 95 % CI 0.29 to 0.60 ) P<0.001 ) . Participants with ≥5 % weight loss at one year had 65 % lower T2D incidence ( HR 0.35 ( 95 % CI 0.22 to 0.56 ) P<0.001 ) ; maintaining ≥5 % weight loss for two and three years further reduced T2D incidence . Recommended cut-points to identify those at high risk for T2D would have identified different proportions of European Diabetes Prevention Study ( EDIPS ) participants with similar hazard-ratios for intervention effect . Conclusions Pooled analysis of EDIPS trial data reinforces evidence for T2D prevention by lifestyle intervention . Analysis showed the preventive effect of ≥5 % weight loss , especially if maintained long term , which has utility for intervention monitoring . Analysis of proposed cut-points demonstrates difficulties in balancing risk and benefit , to efficiently target interventions and suggests evidence is needed to define clinical policy . Trial registration s The Finnish Diabetes Prevention study , Helsinki , Finl and : Clinical Trials.gov ; NCT00518167 The SLIM diabetes prevention study , Maastricht , The Netherl and s : Clinical Trials.gov ; NCT00381186 The EDIPS-Newcastle diabetes prevention study , Newcastle upon Tyne , UK : International St and ard R and omised Controlled Trial Number ; IS RCT N15670600 OBJECTIVE Changing dietary and physical activity habits has the potential to postpone or prevent the development of type 2 diabetes . However , it needs to be assessed whether moderate interventions , in agreement with current guidelines for the general population , are effective . We evaluated the impact of a 2-year combined diet and physical activity intervention program on glucose tolerance in Dutch subjects at increased risk for developing diabetes . RESEARCH METHODS AND PROCEDURES Subjects with glucose intolerance were r and omly assigned to either the lifestyle intervention group ( INT ) or control group ( CON ) . The INT received regular dietary advice and was stimulated to increase their physical activity . The CON received a brief leaflet about healthy diet and increased physical activity . Primary outcome measure was the change in glucose tolerance . RESULTS In total , 88 subjects completed 2 years of intervention ( 40 subjects in the INT , 48 subjects in the CON , mean BMI 29.4 kg/m2 ) . Subjects in the INT reduced their body weight , waist circumference , and ( saturated ) fat intake and improved their aerobic capacity . Two-hour plasma glucose concentration declined from 8.7 to 8.0 mM in the INT and rose from 8.6 to 9.4 mM in the CON ( p < 0.01 ) . Subjects adherent to both the diet and exercise intervention showed the largest reduction in 2-hour glucose levels . DISCUSSION Our results showed that a lifestyle intervention program according to general recommendations improves glucose tolerance , even in a less obese and more physical active population . Furthermore , our results underscore the importance of combining diet and physical activity to improve glucose tolerance and insulin resistance 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 OBJECTIVE To examine associations between type 2 diabetes and fiber , glycemic load ( GL ) , dietary glycemic index ( GI ) , and fiber-rich foods . RESEARCH DESIGN AND METHODS This was a prospect i ve study of 36,787 men and women aged 40 - 69 years without diabetes . For all self-reported cases of diabetes at 4-year follow-up , confirmation of diagnosis was sought from medical practitioners . Case subjects were those who reported diabetes at follow-up and for whom there was no evidence that they did not have type 2 diabetes . Data were analyzed with logistic regression , adjusting for country of birth , physical activity , family history of diabetes , alcohol and energy intake , education , 5-year weight change , sex , and age . RESULTS Follow-up was completed by 31,641 ( 86 % ) participants , and 365 cases were identified . The odds ratio ( OR ) for the highest quartile of white bread intake compared with the lowest was 1.37 ( 95 % CI 1.04 - 1.81 ; P for trend = 0.001 ) . Intakes of carbohydrate ( OR per 200 g/day 0.58 , 0.36 - 0.95 ) , sugars ( OR per 100 g/day 0.61 , 0.47 - 0.79 ) , and magnesium ( OR per 500 mg/day 0.62 , 0.43 - 0.90 ) were inversely associated with incidence of diabetes , whereas intake of starch ( OR per 100 g/day 1.47 , 1.06 - 2.05 ) and dietary GI ( OR per 10 units 1.32 , 1.05 - 1.66 ) were positively associated with diabetes . These relationships were attenuated after adjustment for BMI and waist-to-hip ratio . CONCLUSIONS Reducing dietary GI while maintaining a high carbohydrate intake may reduce the risk of type 2 diabetes . One way to achieve this would be to substitute white bread with low-GI breads Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose Background : Weight loss is a key factor in reducing diabetes risk . The Diabetes Prevention Program ( DPP ) is a completed clinical trial that r and omly assigned individuals at high risk of diabetes to a placebo ( PLBO ) , metformin ( MET ) , or intensive lifestyle intervention ( ILS ) group , which included physical activity ( PA ) and reduced dietary fat intake . Objective : We aim ed to evaluate the associations between diet and weight at baseline and to identify specific dietary factors that predicted weight loss among DPP participants . Methods : Diet was assessed by a food frequency question naire . The associations between intakes of macronutrients and various food groups and body weight among DPP participants at baseline were assessed by linear regression , adjusted for race/ethnicity , age , sex , calorie intake , and PA . Models that predicted weight loss at year 1 were adjusted for baseline weight , change in calorie intake , and change in PA and stratified by treatment allocation ( MET , ILS , and PLBO ) . All results are presented as estimates ± SEs . Results : A total of 3234 participants were enrolled in the DPP ; 2924 had completed dietary data ( 67.5 % women ; mean age : 50.6 ± 10.7 y ) . Adjusted for calorie intake , baseline weight was negatively associated with carbohydrate intake ( -1.14 ± 0.18 kg body weight/100 kcal carbohydrate , P < 0.0001 ) and , specifically , dietary fiber ( -1.26 ± 0.28 kg/5 g fiber , P < 0.0001 ) . Baseline weight was positively associated with total fat ( 1.25 ± 0.21 kg/100 kcal , P < 0.0001 ) , saturated fat ( 1.96 ± 0.46 kg/100 kcal , P < 0.0001 ) , and protein ( 0.21 ± 0.05 kg/100 kcal , P < 0.0001 ) . For all groups , weight loss after 1 y was associated with increases in carbohydrate intake , specifically dietary fiber , and decreases in total fat and saturated fat intake . Conclusions : Higher carbohydrate consumption among DPP participants , specifically high-fiber carbohydrates , and lower total and saturated fat intake best predicted weight loss when adjusted for changes in calorie intake . Our results support the benefits of a high-carbohydrate , high-fiber , low-fat diet in the context of overall calorie reduction leading to weight loss , which may prevent diabetes in high-risk individuals . This trial was registered at clinical trials.gov as NCT00004992 Background / objectives Vegetarian diets are inversely associated with diabetes in Westerners but their impact on Asians — whose pathophysiology differ from Westerners — is unknown . We aim to investigate the association between a vegetarian diet , change in dietary patterns and diabetes risk in a Taiwanese Buddhist population . Methods We prospect ively followed 2918 non-smoking , non-alcohol drinking Buddhists free of diabetes , cancer , and cardiovascular diseases at baseline , for a median of 5 years , with 183 incident diabetes cases confirmed . Diet was assessed through a vali date d food frequency question naire at baseline and a simple question naire during follow-ups . Incident cases of diabetes were ascertained through follow-up question naires , fasting glucose and HbA1C . Stratified Cox Proportional Hazards Regression was used to assess the effect of diets on risk of diabetes . Results Consistent vegetarian diet was associated with 35 % lower hazards ( HR : 0.65 , 95 % CI : 0.46 , 0.92 ) , while converting from a nonvegetarian to a vegetarian pattern was associated with 53 % lower hazards ( HR : 0.47 , 95 % CI : 0.30 , 0.71 ) for diabetes , comparing with nonvegetarians while adjusting for age , gender , education , physical activity , family history of diabetes , follow-up methods , use of lipid-lowering medications , and baseline BMI . Conclusion Vegetarian diet and converting to vegetarian diet may protect against diabetes independent of BMI among Taiwanese BACKGROUND Dietary carbohydrates may influence the development of type 2 ( non-insulin-dependent ) diabetes , for example , through effects on blood glucose and insulin concentrations . OBJECTIVE We examined the relations of baseline intake of carbohydrates , dietary fiber , dietary magnesium , and carbohydrate-rich foods and the glycemic index with incidence of diabetes . DESIGN This was a prospect i ve cohort study of 35988 older Iowa women initially free of diabetes . During 6 y of follow-up , 1141 incident cases of diabetes were reported . RESULTS Total grain , whole-grain , total dietary fiber , cereal fiber , and dietary magnesium intakes showed strong inverse associations with incidence of diabetes after adjustment for potential nondietary confounding variables . Multivariate-adjusted relative risks of diabetes were 1.0 , 0.99 , 0.98 , 0.92 , and 0.79 ( P for trend : 0.0089 ) across quintiles of whole-grain intake ; 1.0 , 1.09 , 1.00 , 0.94 , and 0.78 ( P for trend : 0.005 ) across quintiles of total dietary fiber intake ; and 1.0 , 0.81 , 0.82 , 0.81 , and 0.67 ( P for trend : 0.0003 ) across quintiles of dietary magnesium intake . Intakes of total carbohydrates , refined grains , fruit and vegetables , and soluble fiber and the glycemic index were unrelated to diabetes risk . CONCLUSION These data support a protective role for grains ( particularly whole grains ) , cereal fiber , and dietary magnesium in the development of diabetes in older women BACKGROUND Little is known about the association between eating patterns and type 2 diabetes ( T2D ) risk in women . OBJECTIVE The objective was to examine prospect ively associations between regular breakfast consumption , eating frequency , and T2D risk in women . DESIGN Eating pattern was assessed in 2002 in a cohort of 46,289 US women in the Nurses ' Health Study who were free of T2D , cardiovascular disease , or cancer and were followed for 6 y. We used Cox proportional hazards analysis to evaluate associations with incident T2D . RESULTS We documented 1560 T2D cases during follow-up . After adjustment for known risk factors for T2D-except for body mass index ( BMI ) , a potential mediator-women who consumed breakfast irregularly ( 0 - 6 times/wk ) were at higher risk of T2D than were women who consumed breakfast daily ( RR : 1.28 ; 95 % CI : 1.14 , 1.44 ) . This association was moderately attenuated after adjustment for BMI ( RR : 1.20 ; 95 % CI : 1.07 , 1.35 ) . In comparison with women who ate 3 times/d , the RRs were 1.09 ( 0.84 , 1.41 ) for women who ate 1 - 2 times/d , 1.13 ( 1.00 , 1.27 ) for women who ate 4 - 5 times/d , and 0.99 ( 0.81 , 1.21 ) for women who ate ≥6 times/d . Among irregular breakfast consumers , women with a higher eating frequency ( ≥4 times/d ) had a significantly greater T2D risk ( RR : 1.47 ; 95 % CI : 1.23 , 1.75 ) than did women who consumed breakfast daily and ate 1 - 3 times/d . Adjustment for BMI attenuated this association ( RR : 1.24 ; 95 % CI : 1.04 , 1.48 ) . CONCLUSION Irregular breakfast consumption was associated with a higher T2D risk in women , which was partially but not entirely mediated by BMI Aims /hypothesisWe determined the effects of 6 years of lifestyle intervention in persons with impaired glucose tolerance ( IGT ) on the development of retinopathy , nephropathy and neuropathy over a 20 year period . Methods In 1986 , 577 adults with IGT from 33 clinics in Da Qing , China were r and omly assigned by clinic to a control group or one of three lifestyle intervention groups ( diet , exercise , and diet plus exercise ) . Active intervention was carried out from 1986 to 1992 . In 2006 we conducted a 20 year follow-up study of the original participants to compare the incidence of microvascular complications in the combined intervention group vs the control group . Results Follow-up information was obtained on 542 ( 94 % ) of the 577 original participants . The cumulative incidence of severe retinopathy was 9.2 % in the combined intervention group and 16.2 % in the control group ( p = 0.03 , log-rank test ) . After adjusting for clinic and age , the incidence of severe retinopathy was 47 % lower in the intervention group than the control group ( hazard rate ratio 0.53 , 95 % CI 0.29–0.99 , p = 0.048 ) . No significant differences were found in the incidence of severe nephropathy ( hazard rate ratio 1.05 , 95 % CI 0.16–7.05 , intervention vs control , p = 0.96 ) or in the prevalence of neuropathy ( 8.6 % vs 9.1 % , p = 0.89 ) among the 20 year survivors . Conclusions /interpretationLifestyle intervention for 6 years in IGT was associated with a 47 % reduction in the incidence of severe , vision-threatening retinopathy over a 20 year interval , primarily due to the reduced incidence of diabetes in the intervention group . However , similar benefits were not seen for nephropathy or neuropathy Prevention of type 2 diabetes by intensive lifestyle intervention design ed to achieve and maintain ideal body weight was assessed in subjects with impaired glucose tolerance ( IGT ) . Male subjects with IGT recruited from health-screening examinees were r and omly assigned in a 4:1 ratio to a st and ard intervention group ( control group ) and intensive intervention group ( intervention group ) . The final numbers of subjects were 356 and 102 , respectively . The subjects in the control group and in the intervention group were advised to maintain body mass index ( BMI ) of < 24.0 kg/m2 and of < 22.0 kg/m2 , respectively , by diet and exercise . In the intervention group , detailed instructions on lifestyle were repeated every 3 - 4 months during hospital visits . Diabetes was judged to have developed when two or more consecutive fasting plasma glucose ( FPG ) values exceeded 140 mg/dl . A 100 g oral glucose tolerance test was performed every 6 months to detect improvement of glucose tolerance . The subjects were seen in an ordinary outpatient clinic . The cumulative 4-year incidence of diabetes was 9.3 % in the control group , versus 3.0 % in the intervention group , and the reduction in risk of diabetes was 67.4 % ( P < 0.001 ) . Body weight decreased by 0.39 kg in the control group and by 2.18 kg in the intervention group ( P < 0.001 ) . The control group was subclassified according to increase and decrease in body weight . The incidence of diabetes was positively correlated with the changes in body weight , and the improvement in glucose tolerance was negatively correlated . Subjects with higher FPG at baseline developed diabetes at a higher rate than those with lower FPG . Higher 2h plasma glucose values and higher BMI values at baseline were also associated with a higher incidence of diabetes , but the differences were not significant . Subjects with a low insulinogenic index ( DeltaIRI/DeltaPG 30 min after an oral glucose load ) developed diabetes at a significantly higher rate than those with a normal insulinogenic index . Comparison of the BMI data and incidence of diabetes in five diabetes prevention studies by lifestyle intervention revealed a linear correlation between the incidence of diabetes and the BMI values , with the exception of the DaQing Study . However , the slope of the reduction in incidence of diabetes in the intensive intervention groups was steeper than expected simply on the basis of the reduction of BMI , suggesting that the effect of lifestyle intervention can not be solely ascribed to the body weight reduction . We conclude that lifestyle intervention aim ed at achieving ideal body weight in men with IGT is effective and can be conducted in an outpatient clinic setting Objective To quantify the association between a combination of healthy lifestyle factors before pregnancy ( healthy body weight , healthy diet , regular exercise , and not smoking ) and the risk of gestational diabetes . Design Prospect i ve cohort study . Setting Nurses ’ Health Study II , United States . Participants 20 136 singleton live births in 14 437 women without chronic disease . Main outcome measure Self reported incident gestational diabetes diagnosed by a physician , vali date d by medical records in a previous study . Results Incident first time gestational diabetes was reported in 823 pregnancies . Each lifestyle factor measured was independently and significantly associated with risk of gestational diabetes . The combination of three low risk factors ( non-smoker , ≥150 minutes a week of moderate to vigorous physical activity , and healthy eating ( top two fifths of Alternate Healthy Eating Index-2010 adherence score ) ) was associated with a 41 % lower risk of gestational diabetes compared with all other pregnancies ( relative risk 0.59 , 95 % confidence interval 0.48 to 0.71 ) . Addition of body mass index ( BMI ) < 25 before pregnancy ( giving a combination of four low risk factors ) was associated with a 52 % lower risk of gestational diabetes compared with all other pregnancies ( relative risk 0.48 , 0.38 to 0.61 ) . Compared with pregnancies in women who did not meet any of the low risk lifestyle factors , those meeting all four criteria had an 83 % lower risk of gestational diabetes ( relative risk 0.17 , 0.12 to 0.25 ) . The population attributable risk percentage of the four risk factors in combination ( smoking , inactivity , overweight , and poor diet ) was 47.5 % ( 95 % confidence interval 35.6 % to 56.6 % ) . A similar population attributable risk percentage ( 49.2 % ) was observed when the distributions of the four low risk factors from the US National Health and Nutrition Examination Survey ( 2007 - 10 ) data were applied to the calculation . Conclusions Adherence to a low risk lifestyle before pregnancy is associated with a low risk of gestational diabetes and could be an effective strategy for the prevention of gestational diabetes Background / Objectives : There is still a need for scientific evidence about which foods characterize a healthy diet in terms of primary prevention of major chronic diseases . Therefore , we aim ed to give a comprehensive overview on health-related foods , based on 8 years of follow-up of the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Potsdam study .Subjects/ Methods : We used data from 23 531 participants of the EPIC-Potsdam study to analyse the associations between 45 single food groups and risk of major chronic diseases , namely , cardiovascular diseases ( CVD ) , type 2 diabetes and cancer using multivariable-adjusted Cox regression . Habitual dietary intake was assessed at baseline using food-frequency question naires . Incident chronic diseases were determined by self-administered follow-up question naires and medically verified , based on inquiry to treating physicians , cancer registries or through death certificates . Results : During follow-up , 363 incident CVD , 837 type 2 diabetes and 844 cancer cases were identified . Higher intakes of whole-grain bread , raw vegetables , coffee and cakes and cookies were found to be significantly associated with a lower risk of chronic diseases . Conversely , higher intakes of low-fat dairy , butter , red meat and sauce were associated with higher risks of chronic diseases . Conclusion : Overall , a healthy diet was characterized by a high consumption of whole-grain bread , raw vegetables and a low consumption of red meat and possibly butter , which is generally in line with previous findings . The paradoxical findings concerning the potential health benefit of coffee as well as cakes and cookies are interesting and should be investigated further 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 Lifestyle interventions reduce the incidence of type 2 diabetes among individuals with impaired glucose tolerance ( IGT ) . However , it is unknown whether this is due to improved insulin sensitivity or insulin secretion . We investigated at baseline insulin sensitivity and insulin secretion applying frequently sample d intravenous glucose tolerance test ( FSIGT ) in 87 of 101 obese middle-aged subjects with IGT r and omized into an intervention or a control group in the Finnish Diabetes Prevention Study . FSIGT was repeated after 4 years in 52 people . There were no significant differences in any of the baseline anthropometric or metabolic characteristics between the groups . The 4-year weight and waist circumference decreases were greater in the intervention than in the control group ( P = 0.043 and P = 0.025 , respectively ) . At 4-year examination , insulin sensitivity ( Si ) tended to be higher in the intervention group ( the difference between the mean values 36 % ; P = 0.067 , and P = 0.136 after adjustment for age , sex , BMI , and baseline Si value ) . There was strong correlation between the 4-year changes in Si and weight ( r = -0.628 and r = -0.710 , for intervention and control groups ; P < 0.001 for both ) . In the entire group , Si improved by 64 % in the highest tertile of weight loss but deteriorated by 24 % in those who gained weight ( lowest tertile ) . Acute insulin response declined significantly in the control group . In conclusion , Si markedly improved by weight reduction during the 4-year follow-up of individuals with IGT . Insulin secretion remained constant for years in individuals with IGT who were able to lose weight BACKGROUND & AIMS Legumes , a low-energy , nutrient-dense and low glycemic index food , have shown beneficial effects on glycemic control and adiposity . As such , legumes are widely recommended in diabetic diets , even though there is little evidence that their consumption protects against type 2 diabetes . Therefore the aim of the present study was to examine the associations between consumption of total legumes and specific subtypes , and type 2 diabetes risk . We also investigated the effect of theoretically substituting legumes for other protein- or carbohydrate-rich foods . METHODS Prospect i ve assessment of 3349 participants in the PREvención con DIeta MEDiterránea ( PREDIMED ) study without type 2 diabetes at baseline . Dietary information was assessed at baseline and yearly during follow-up . We used Cox regression models to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( 95 % CIs ) for type-2 diabetes incidence according to quartiles of cumulative average consumption of total legumes , lentils , chickpeas , dry beans and fresh peas . RESULTS During a median follow-up of 4.3 years , 266 new cases of type 2 diabetes occurred . Individuals in the highest quartile of total legume and lentil consumption had a lower risk of diabetes than those in the lowest quartile ( HR : 0.65 ; 95 % CI : 0.43 , 0.96 ; P-trend = 0.04 ; and HR : 0.67 ; 95 % CI : 0.46 - 0.98 ; P-trend = 0.05 , respectively ) . A borderline significant association was also observed for chickpeas consumption ( HR 0.68 ; 95 % CI : 0.46 , 1.00 ; P-trend = 0.06 ) . Substitutions of half a serving/day of legumes for similar servings of eggs , bread , rice or baked potato was associated with lower risk of diabetes incidence . CONCLUSIONS A frequent consumption of legumes , particularly lentils , in the context of a Mediterranean diet , may provide benefits on type 2 diabetes prevention in older adults at high cardiovascular risk . TRIAL REGISTRATION The trial is registered at http://www.controlled-trials.com ( IS RCT N35739639 ) . Registration date : 5th October 2005 BACKGROUND In the 2.8 years of the Diabetes Prevention Program ( DPP ) r and omised clinical trial , diabetes incidence in high-risk adults was reduced by 58 % with intensive lifestyle intervention and by 31 % with metformin , compared with placebo . We investigated the persistence of these effects in the long term . METHODS All active DPP participants were eligible for continued follow-up . 2766 of 3150 ( 88 % ) enrolled for a median additional follow-up of 5.7 years ( IQR 5.5 - 5.8 ) . 910 participants were from the lifestyle , 924 from the metformin , and 932 were from the original placebo groups . On the basis of the benefits from the intensive lifestyle intervention in the DPP , all three groups were offered group-implemented lifestyle intervention . Metformin treatment was continued in the original metformin group ( 850 mg twice daily as tolerated ) , with participants unmasked to assignment , and the original lifestyle intervention group was offered additional lifestyle support . The primary outcome was development of diabetes according to American Diabetes Association criteria . Analysis was by intention-to-treat . This study is registered with Clinical Trials.gov , number NCT00038727 . FINDINGS During the 10.0-year ( IQR 9.0 - 10.5 ) follow-up since r and omisation to DPP , the original lifestyle group lost , then partly regained weight . The modest weight loss with metformin was maintained . Diabetes incidence rates during the DPP were 4.8 cases per 100 person-years ( 95 % CI 4.1 - 5.7 ) in the intensive lifestyle intervention group , 7.8 ( 6.8 - 8.8 ) in the metformin group , and 11.0 ( 9.8 - 12.3 ) in the placebo group . Diabetes incidence rates in this follow-up study were similar between treatment groups : 5.9 per 100 person-years ( 5.1 - 6.8 ) for lifestyle , 4.9 ( 4.2 - 5.7 ) for metformin , and 5.6 ( 4.8 - 6.5 ) for placebo . Diabetes incidence in the 10 years since DPP r and omisation was reduced by 34 % ( 24 - 42 ) in the lifestyle group and 18 % ( 7 - 28 ) in the metformin group compared with placebo . INTERPRETATION During follow-up after DPP , incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group , but the cumulative incidence of diabetes remained lowest in the lifestyle group . Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years . FUNDING National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) 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 BACKGROUND It has been postulated that a diet high in legumes may be beneficial for the prevention of type 2 diabetes mellitus ( type 2 DM ) . However , data linking type 2 DM risk and legume intake are limited . OBJECTIVE The objective of the study was to examine the association between legume and soy food consumption and self-reported type 2 DM . DESIGN The study was conducted in a population -based prospect i ve cohort of middle-aged Chinese women . We followed 64,227 women with no history of type 2 DM , cancer , or cardiovascular disease at study recruitment for an average of 4.6 y. Participants completed in-person interviews that collected information on diabetes risk factors , including dietary intake and physical activity in adulthood . Anthropometric measurements were taken . Dietary intake was assessed with a vali date d food-frequency question naire at the baseline survey and at the first follow-up survey administered 2 - 3 y after study recruitment . RESULTS We observed an inverse association between quintiles of total legume intake and 3 mutually exclusive legume groups ( peanuts , soybeans , and other legumes ) and type 2 DM incidence . The multivariate-adjusted relative risk of type 2 DM for the upper quintile compared with the lower quintile was 0.62 ( 95 % CI : 0.51 , 0.74 ) for total legumes and 0.53 ( 95 % CI : 0.45 , 0.62 ) for soybeans . The association between soy products ( other than soy milk ) and soy protein consumption ( protein derived from soy beans and their products ) with type 2 DM was not significant . CONCLUSIONS Consumption of legumes , soybeans in particular , was inversely associated with the risk type 2 DM Clinical trials have demonstrated that lifestyle changes can prevent type 2 diabetes , but the importance of leisure-time physical activity ( LTPA ) is still unclear . We carried out post hoc analyses on the role of LTPA in preventing type 2 diabetes in 487 men and women with impaired glucose tolerance who had completed 12-month LTPA question naires . The subjects were participants in the Finnish Diabetes Prevention Study , a r and omized controlled trial of lifestyle changes including diet , weight loss , and LTPA . There were 107 new cases of diabetes during the 4.1-year follow-up period . Individuals who increased moderate-to-vigorous LTPA or strenuous , structured LTPA the most were 63 - 65 % less likely to develop diabetes . Adjustment for changes in diet and body weight during the study attenuated the association somewhat ( upper versus lower third : moderate-to-vigorous LTPA , relative risk 0.51 , 95 % CI 0.26 - 0.97 ; strenuous , structured LTPA , 0.63 , 0.35 - 1.13 ) . Low-intensity and lifestyle LTPA and walking also conferred benefits , consistent with the finding that the change in total LTPA ( upper versus lower third : 0.34 , 0.19 - 0.62 ) was the most strongly associated with incident diabetes . Thus increasing physical activity may substantially reduce the incidence of type 2 diabetes in high-risk individuals OBJECTIVE To date no clinical trials have evaluated the role of dietary patterns on the incidence of microvascular diabetes complications . We hypothesized that a nutritional intervention based on the Mediterranean diet ( MedDiet ) would have greater protective effect on diabetic retinopathy and nephropathy than a low-fat control diet . RESEARCH DESIGN AND METHODS This was a post hoc analysis of a cohort of patients with type 2 diabetes participating in the PREvención con DIeta MEDiterránea ( PREDIMED ) study , a multicenter r and omized nutritional intervention trial conducted in a population at high cardiovascular risk . Individuals with type 2 diabetes who were free of microvascular complications at enrollment ( n = 3,614 , aged 55–80 years ) were r and omly assigned to one of three dietary interventions : MedDiet supplemented with extravirgin olive oil ( MedDiet+EVOO ) , MedDiet supplemented with mixed nuts ( MedDiet+Nuts ) , or a low-fat control diet . Two independent outcomes were considered : new onset of diabetic retinopathy and nephropathy . Hazard ratios ( HRs ) were calculated using multivariable-adjusted Cox regression . RESULTS During a median follow-up of 6.0 years , we identified 74 new cases of retinopathy and 168 of nephropathy . Compared with the control diet , multivariable-adjusted HRs for diabetic retinopathy were 0.56 ( 95 % CI 0.32–0.97 ) for the MedDiet+EVOO and 0.63 ( 0.35–1.11 ) for the MedDiet+Nuts . No between-group differences were found for nephropathy . When the yearly up date d information on adherence to the MedDiet was considered , the HR for retinopathy in the highest versus the lowest quintile was 0.34 ( 0.13–0.89 ; P = 0.001 for trend ) . No significant associations were found for nephropathy . CONCLUSIONS A MedDiet enriched with EVOO may protect against diabetic retinopathy but not diabetic nephropathy Background The Finnish Diabetes Prevention Study ( DPS ) was a r and omized controlled trial , which showed that it is possible to prevent type 2 diabetes by lifestyle changes . The aim of the present study was to examine whether the lifestyle intervention had an effect on the ten-year mortality and cardiovascular morbidity in the DPS participants originally r and omized either into an intervention or control group . Furthermore , we compared these results with a population -based cohort comprising individuals of varying glucose tolerance states . Methods and Findings Middle-aged , overweight people with IGT ( n = 522 ) were r and omized into intensive intervention ( including physical activity , weight reduction and dietary counseling ) , or control “ mini-intervention ” group . Median length of the intervention period was 4 years and the mean follow-up was 10.6 years . The population -based reference study cohort included 1881 individuals ( 1570 with normal glucose tolerance , 183 with IGT , 59 with screen-detected type 2 diabetes , 69 with previously known type 2 diabetes ) with the mean follow-up of 13.8 years . Mortality and cardiovascular morbidity data were collected from the national Hospital Discharge Register and Causes of Death Register . Among the DPS participants who consented for register linkage ( n = 505 ) , total mortality ( 2.2 vs. 3.8 per 1000 person years , hazard ratio HR = 0.57 , 95 % CI 0.21–1.58 ) and cardiovascular morbidity ( 22.9 vs. 22.0 per 1000 person years , HR = 1.04 , 95 % CI 0.72–1.51 ) did not differ significantly between the intervention and control groups . Compared with the population -based cohort with impaired glucose tolerance , adjusted HRs were 0.21 ( 95 % CI 0.09–0.52 ) and 0.39 ( 95 % CI 0.20–0.79 ) for total mortality , and 0.89 ( 95 % CI 0.62–1.27 ) and 0.87 ( 0.60–1.27 ) for cardiovascular morbidity in the intervention and control groups of the DPS , respectively . The risk of death in DPS combined cohort was markedly lower than in FINRISK IGT cohort ( adjusted HR 0.30 , 95 % CI 0.17–0.54 ) , but there was no significant difference in the risk of CVD ( adjusted HR 0.88 , 95 % CI 0.64–1.21 ) . Conclusions Lifestyle intervention among persons with IGT did not decrease cardiovascular morbidity during the first 10 years of follow-up . However , the statistical power may not be sufficient to detect small differences between the intervention and control groups . Low total mortality among participants of the DPS compared with individuals with IGT in the general population could be ascribed to a lower cardiovascular risk profile at baseline and regular follow-up . Trial Registration Clinical Trials.gov BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P<0.001 ) in the intervention group . The reduction in the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects Aims /hypothesisLifestyle modification helps in the primary prevention of diabetes in multiethnic American , Finnish and Chinese population s. In a prospect i ve community-based study , we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger , leaner and more insulin resistant than the above population s. Methods We r and omised 531 ( 421 men 110 women ) subjects with IGT ( mean age 45.9±5.7 years , BMI 25.8±3.5 kg/m2 ) into four groups . Group 1 was the control , Group 2 was given advice on lifestyle modification ( LSM ) , Group 3 was treated with metformin ( MET ) and Group 4 was given LSM plus MET . The primary outcome measure was type 2 diabetes as diagnosed using World Health Organization criteria . Results The median follow-up period was 30 months , and the 3-year cumulative incidences of diabetes were 55.0 % , 39.3 % , 40.5 % and 39.5 % in Groups 1–4 , respectively . The relative risk reduction was 28.5 % with LSM ( 95 % CI 20.5–37.3 , p=0.018 ) , 26.4 % with MET ( 95 % CI 19.1–35.1 , p=0.029 ) and 28.2 % with LSM + MET ( 95 % CI 20.3–37.0 , p=0.022 ) , as compared with the control group . The number needed to treat to prevent one incident case of diabetes was 6.4 for LSM , 6.9 for MET and 6.5 for LSM + MET . Conclusions /interpretationProgression of IGT to diabetes is high in native Asian Indians . Both LSM and MET significantly reduced the incidence of diabetes in Asian Indians with IGT ; there was no added benefit from combining them BACKGROUND Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes , at least as long as the intervention continues . In the extended follow-up of the Finnish Diabetes Prevention Study , we assessed the extent to which the originally-achieved lifestyle changes and risk reduction remain after discontinuation of active counselling . METHODS Overweight , middle-aged men ( n=172 ) and women ( n=350 ) with impaired glucose tolerance were r and omly assigned to intensive lifestyle intervention or control group . After a median of 4 years of active intervention period , participants who were still free of diabetes were further followed up for a median of 3 years , with median total follow-up of 7 years . Diabetes incidence , bodyweight , physical activity , and dietary intakes of fat , saturated fat , and fibre were measured . FINDINGS During the total follow-up , the incidence of type 2 diabetes was 4.3 and 7.4 per 100 person-years in the intervention and control group , respectively ( log-rank test p=0.0001 ) , indicating 43 % reduction in relative risk . The risk reduction was related to the success in achieving the intervention goals of weight loss , reduced intake of total and saturated fat and increased intake of dietary fibre , and increased physical activity . Beneficial lifestyle changes achieved by participants in the intervention group were maintained after the discontinuation of the intervention , and the corresponding incidence rates during the post-intervention follow-up were 4.6 and 7.2 ( p=0.0401 ) , indicating 36 % reduction in relative risk . INTERPRETATION Lifestyle intervention in people at high risk for type 2 diabetes result ed in sustained lifestyle changes and a reduction in diabetes incidence , which remained after the individual lifestyle counselling was stopped Summary From a previously reported 5-year screening programme of 6,956 47–49-year-old Malmö males , a series of 41 subjects with early-stage Type 2 ( non-insulin-dependent ) diabetes mellitus and 181 subjects with impaired glucose tolerance were selected for prospect i ve study and to test the feasibility aspect of long-term intervention with an emphasis on life-style changes . A 5-year protocol , including an initial 6-months ( r and omised ) pilot study , consisting of dietary treatment and /or increase of physical activity or training with annual check-ups , was completed by 90 % of subjects . Body weight was reduced by 2.3–3.7 % among participants , whereas values increased by 0.5–1.7 % in non-intervened subjects with impaired glucose tolerance and in normal control subjects ( p<0.0001 ) ; maximal oxygen uptake ( ml · min−1 · kg−1 ) was increased by 10–14 % vs decreased by 5–9 % , respectively ( p<0.0001 ) . Glucose tolerance was normalized in > 50 % of subjects with impaired glucose tolerance , the accumulated incidence of diabetes was 10.6 % , and more than 50 % of the diabetic patients were in remission after a mean follow-up of 6 years . Blood pressure , lipids , and hyperinsulinaemia were reduced and early insulin responsiveness to glucose loading preserved . Improvement in glucose tolerance was correlated to weight reduction ( r=0.19 , p<0.02 ) and increased fitness ( r=0.22 , p<0.02 ) . Treatment was safe , and mortality was low ( in fact 33 % lower than in the remainder of the cohort ) . We conclude that long-term intervention in the form of diet and physical exercise is feasible even on a large scale , and that substantial metabolic improvement can be achieved which may contribute to prevent or postpone manifest diabetes 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 Although obesity is the most important risk factor for type 2 diabetes , evidence is emerging that certain foods and dietary factors may be associated with diabetes . To examine the association between major dietary patterns and risk of type 2 diabetes mellitus in a cohort of women . METHODS We prospect ively assessed the associations between major dietary patterns and risk of type 2 diabetes in women . Dietary information was collected in 1984 , 1986 , 1990 , and 1994 from 69,554 women aged 38 to 63 years without a history of diabetes , cardiovascular disease , or cancer in 1984 . We conducted factor analysis and identified 2 major dietary patterns : " prudent " and " Western . " We then calculated pattern scores for each participant and examined prospect ively the associations between dietary pattern scores and type 2 diabetes risks . RESULTS The prudent pattern was characterized by higher intakes of fruits , vegetables , legumes , fish , poultry , and whole grains , while the Western pattern included higher intakes of red and processed meats , sweets and desserts , french fries , and refined grains . During 14 years of follow-up , we identified 2699 incident cases of type 2 diabetes . After adjusting for potential confounders , we observed a relative risk for diabetes of 1.49 ( 95 % confidence interval [ CI ] , 1.26 - 1.76 , P for trend , < .001 ) when comparing the highest to lowest quintiles of the Western pattern . Positive associations were also observed between type 2 diabetes and red meat and other processed meats . The relative risk for diabetes for every 1-serving increase in intake is 1.26 ( 95 % CI , 1.21 - 1.42 ) for red meat , 1.38 ( 95 % CI , 1.23 - 1.56 ) for total processed meats , 1.73 ( 95 % CI , 1.39 - 2.16 ) for bacon , 1.49 ( 95 % CI , 1.04 - 2.11 ) for hot dogs , and 1.43 ( 95 % CI , 1.22 - 1.69 ) for processed meats . CONCLUSION The Western pattern , especially a diet higher in processed meats , may increase the risk of type 2 diabetes in women OBJECTIVE Individuals with impaired glucose tolerance ( IGT ) have a high risk of developing NIDDM . The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM , i.e. , reduce the incidence of NIDDM , and thereby reduce the overall incidence of diabetic complications , such as cardiovascular , renal , and retinal disease , and the excess mortality attributable to these complications . RESEARCH DESIGN AND METHODS In 1986 , 110,660 men and women from 33 health care clinics in the city of Da Qing , China , were screened for IGT and NIDDM . Of these individuals , 577 were classified ( using World Health Organization criteria ) as having IGT . Subjects were r and omized by clinic into a clinical trial , either to a control group or to one of three active treatment groups : diet only , exercise only , or diet plus exercise . Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM . Cox 's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment . RESULTS The cumulative incidence of diabetes at 6 years was 67.7 % ( 95 % CI , 59.8–75.2 ) in the control group compared with 43.8 % ( 95 % CI , 35.5–52.3 ) in the diet group , 41.1 % ( 95 % CI , 33.4–49.4 ) in the exercise group , and 46.0 % ( 95 % CI , 37.3–54.7 ) in the diet-plus-exercise group ( P < 0.05 ) . When analyzed by clinic , each of the active intervention groups differed significantly from the control clinics ( P < 0.05 ) . The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight ( BMI < or ≥ 25 kg/m2 ) . In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose , the diet , exercise , and diet-plus-exercise interventions were associated with 31 % ( P < 0.03 ) , 46 % ( P < 0.0005 ) , and 42 % ( P < 0.005 ) reductions in risk of developing diabetes , respectively . CONCLUSIONS Diet and /or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT Diets high in protein have shown positive effects on short-term weight reduction and glycaemic control . However , the underst and ing of how dietary macronutrient composition relates to long-term risk of type 2 diabetes is limited . The aim of the present study was to examine intakes of macronutrients , fibre and protein sources in relation to incident type 2 diabetes . In total , 27 140 individuals , aged 45 - 74 years , from the population -based Malmö Diet and Cancer cohort , were included . Dietary data were collected with a modified diet history method , including registration of cooked meals . During 12 years of follow-up , 1709 incident type 2 diabetes cases were identified . High protein intake was associated with increased risk of type 2 diabetes ( hazard ratio ( HR ) 1.27 for highest compared with lowest quintile ; 95 % CI 1.08 , 1.49 ; P for trend = 0.01 ) . When protein consumption increased by 5 % of energy at the expense of carbohydrates ( HR 1.20 ; 95 % CI 1.09 , 1.33 ) or fat ( HR 1.21 ; 95 % CI 1.09 , 1.33 ) , increased diabetes risk was observed . Intakes in the highest quintiles of processed meat ( HR 1.16 ; 95 % CI 1.00 , 1.36 ; P for trend = 0.01 ) and eggs ( HR 1.21 ; 95 % CI 1.04 , 1.41 ; P for trend = 0.02 ) were associated with increased risk . Intake of fibre-rich bread and cereals was inversely associated with type 2 diabetes ( HR 0.84 ; 95 % CI 0.73 , 0.98 ; P for trend = 0.004 ) . In conclusion , results from the present large population -based prospect i ve study indicate that high protein intake is associated with increased risk of type 2 diabetes . Replacing protein with carbohydrates may be favourable , especially if fibre-rich breads and cereals are chosen as carbohydrate sources BACKGROUND Intensive lifestyle interventions can reduce the incidence of type 2 diabetes in people with impaired glucose tolerance , but how long these benefits extend beyond the period of active intervention , and whether such interventions reduce the risk of cardiovascular disease ( CVD ) and mortality , is unclear . We aim ed to assess whether intensive lifestyle interventions have a long-term effect on the risk of diabetes , diabetes-related macrovascular and microvascular complications , and mortality . METHODS In 1986 , 577 adults with impaired glucose tolerance from 33 clinics in China were r and omly assigned to either the control group or to one of three lifestyle intervention groups ( diet , exercise , or diet plus exercise ) . Active intervention took place over 6 years until 1992 . In 2006 , study participants were followed-up to assess the long-term effect of the interventions . The primary outcomes were diabetes incidence , CVD incidence and mortality , and all-cause mortality . FINDINGS Compared with control participants , those in the combined lifestyle intervention groups had a 51 % lower incidence of diabetes ( hazard rate ratio [ HRR ] 0.49 ; 95 % CI 0.33 - 0.73 ) during the active intervention period and a 43 % lower incidence ( 0.57 ; 0.41 - 0.81 ) over the 20 year period , controlled for age and clustering by clinic . The average annual incidence of diabetes was 7 % for intervention participants versus 11 % in control participants , with 20-year cumulative incidence of 80 % in the intervention groups and 93 % in the control group . Participants in the intervention group spent an average of 3.6 fewer years with diabetes than those in the control group . There was no significant difference between the intervention and control groups in the rate of first CVD events ( HRR 0.98 ; 95 % CI 0.71 - 1.37 ) , CVD mortality ( 0.83 ; 0.48 - 1.40 ) , and all-cause mortality ( 0.96 ; 0.65 - 1.41 ) , but our study had limited statistical power to detect differences for these outcomes . INTERPRETATION Group-based lifestyle interventions over 6 years can prevent or delay diabetes for up to 14 years after the active intervention . However , whether lifestyle intervention also leads to reduced CVD and mortality remains unclear BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin BACKGROUND Little is known about the association between eating patterns and type 2 diabetes ( T2D ) risk . OBJECTIVE The objective of this study was to prospect ively examine associations between breakfast omission , eating frequency , snacking , and T2D risk in men . DESIGN Eating patterns were assessed in 1992 in a cohort of 29,206 US men in the Health Professionals Follow-Up Study who were free of T2D , cardiovascular disease , and cancer and were followed for 16 y. We used Cox proportional hazards analysis to evaluate associations with incident T2D . RESULTS We documented 1944 T2D cases during follow-up . After adjustment for known risk factors for T2D , including BMI , men who skipped breakfast had 21 % higher risk of T2D than did men who consumed breakfast ( RR : 1.21 ; 95 % CI : 1.07 , 1.35 ) . Compared with men who ate 3 times/d , men who ate 1 - 2 times/d had a higher risk of T2D ( RR : 1.25 ; 95 % CI : 1.08 , 1.45 ) . These findings persisted after stratification by BMI or diet quality . Additional snacks beyond the 3 main meals ( breakfast , lunch , and dinner ) were associated with increased T2D risk , but these associations were attenuated after adjustment for BMI . CONCLUSIONS Breakfast omission was associated with an increased risk of T2D in men even after adjustment for BMI . A direct association between snacking between meals and T2D risk was mediated by BMI BACKGROUND TCF7L2 is the strongest locus linked to type 2 diabetes that has been identified thus far , and rs7903146 is the most significantly associated variant . Few intervention studies have shown that it has negative effects on metabolic improvement after lifestyle programs . OBJECTIVE Our objective was to assess the effects of this variant on lifestyle intervention-induced changes in glucose values and metabolic variables at 1- and 4-y follow-ups . DESIGN The rs7903146 variant was genotyped in 335 nondiabetic , dysmetabolic participants in a r and omized lifestyle intervention trial . RESULTS Subjects with the unfavorable TT genotype showed higher values of fasting glucose and lower homeostasis model assessment of beta cell function at baseline . Lifestyle modifications were successful in the amelioration of metabolic traits in all genetic subgroups after 1 y. At 4-y follow-up most of the metabolic benefits had disappeared . In a multiple regression model , values for glucose and homeostasis model assessment of beta cell function at 4 y were significantly associated with the T allele ( for glucose and homeostasis model assessment s , respectively : beta = 6.6 ; 95 % CI : 2.5 , 10.7 ; P = 0.001 ; and beta = -0.37 ; 95 % CI : -0.54 , -0.20 ; P < 0.001 ) but not with intervention . There was no interaction between genotype and intervention . After 1 y , impaired fasting glucose and diabetes incidence were inversely associated with intervention . After 4 y , the presence of a T allele was associated with impaired fasting glucose ( odds ratio : 3.04 ; 95 % CI : 1.53 , 6.04 ; P = 0.001 ) and diabetes ( odds ratio : 2.63 ; 95 % CI : 1.00 , 6.96 ; P = 0.05 ) but not with intervention . CONCLUSIONS Lifestyle modifications improved the metabolic pattern in all genetic subgroups . At the end of the trial , however , weight gain occurred , and carriers of the T allele developed first hyperglycemia and decreased insulin secretion , which suggests the need for different " after-care " preventive approaches tailored to each genotype 's metabolic risk BACKGROUND Type 2 diabetes is a chronic disorder that requires lifelong treatment . We aim ed to assess whether intensive weight management within routine primary care would achieve remission of type 2 diabetes . METHODS We did this open-label , cluster-r and omised trial ( DiRECT ) at 49 primary care practice s in Scotl and and the Tyneside region of Engl and . Practice s were r and omly assigned ( 1:1 ) , via a computer-generated list , to provide either a weight management programme ( intervention ) or best- practice care by guidelines ( control ) , with stratification for study site ( Tyneside or Scotl and ) and practice list size ( > 5700 or ≤5700 ) . Participants , carers , and research assistants who collected outcome data were aware of group allocation ; however , allocation was concealed from the study statistician . We recruited individuals aged 20 - 65 years who had been diagnosed with type 2 diabetes within the past 6 years , had a body-mass index of 27 - 45 kg/m2 , and were not receiving insulin . The intervention comprised withdrawal of antidiabetic and antihypertensive drugs , total diet replacement ( 825 - 853 kcal/day formula diet for 3 - 5 months ) , stepped food re introduction ( 2 - 8 weeks ) , and structured support for long-term weight loss maintenance . Co- primary outcomes were weight loss of 15 kg or more , and remission of diabetes , defined as glycated haemoglobin ( HbA1c ) of less than 6·5 % ( < 48 mmol/mol ) after at least 2 months off all antidiabetic medications , from baseline to 12 months . These outcomes were analysed hierarchically . This trial is registered with the IS RCT N registry , number 03267836 . FINDINGS Between July 25 , 2014 , and Aug 5 , 2017 , we recruited 306 individuals from 49 intervention ( n=23 ) and control ( n=26 ) general practice s ; 149 participants per group comprised the intention-to-treat population . At 12 months , we recorded weight loss of 15 kg or more in 36 ( 24 % ) participants in the intervention group and no participants in the control group ( p<0·0001 ) . Diabetes remission was achieved in 68 ( 46 % ) participants in the intervention group and six ( 4 % ) participants in the control group ( odds ratio 19·7 , 95 % CI 7·8 - 49·8 ; p<0·0001 ) . Remission varied with weight loss in the whole study population , with achievement in none of 76 participants who gained weight , six ( 7 % ) of 89 participants who maintained 0 - 5 kg weight loss , 19 ( 34 % ) of 56 participants with 5 - 10 kg loss , 16 ( 57 % ) of 28 participants with 10 - 15 kg loss , and 31 ( 86 % ) of 36 participants who lost 15 kg or more . Mean bodyweight fell by 10·0 kg ( SD 8·0 ) in the intervention group and 1·0 kg ( 3·7 ) in the control group ( adjusted difference -8·8 kg , 95 % CI -10·3 to -7·3 ; p<0·0001 ) . Quality of life , as measured by the EuroQol 5 Dimensions visual analogue scale , improved by 7·2 points ( SD 21·3 ) in the intervention group , and decreased by 2·9 points ( 15·5 ) in the control group ( adjusted difference 6·4 points , 95 % CI 2·5 - 10·3 ; p=0·0012 ) . Nine serious adverse events were reported by seven ( 4 % ) of 157 participants in the intervention group and two were reported by two ( 1 % ) participants in the control group . Two serious adverse events ( biliary colic and abdominal pain ) , occurring in the same participant , were deemed potentially related to the intervention . No serious adverse events led to withdrawal from the study . INTERPRETATION Our findings show that , at 12 months , almost half of participants achieved remission to a non-diabetic state and off antidiabetic drugs . Remission of type 2 diabetes is a practical target for primary care . FUNDING Diabetes UK Aims /hypothesisThis study aim ed to determine whether lifestyle intervention lasting for 4 years affected diabetes incidence , body weight , glycaemia or lifestyle over 13 years among individuals at high risk of type 2 diabetes . Methods Overweight , middle-aged men ( n = 172 ) and women ( n = 350 ) with impaired glucose tolerance were r and omised in 1993–1998 to an intensive lifestyle intervention group ( n = 265 ) , aim ing at weight reduction , dietary modification and increased physical activity , or to a control group ( n = 257 ) that received general lifestyle information . The primary outcome was a diagnosis of diabetes based on annual OGTTs . Secondary outcomes included changes in body weight , glycaemia , physical activity and diet . After active intervention ( median 4 years , range 1–6 years ) , participants still free of diabetes and willing to continue their participation ( 200 in the intervention group and 166 in the control group ) were further followed until diabetes diagnosis , dropout or the end of 2009 , with a median total follow-up of 9 years and a time span of 13 years from baseline . Results During the total follow-up the adjusted HR for diabetes ( intervention group vs control group ) was 0.614 ( 95 % CI 0.478 , 0.789 ; p < 0.001 ) . The corresponding HR during the post-intervention follow-up was 0.672 ( 95 % CI 0.477 , 0.947 ; p = 0.023 ) . The former intervention group participants sustained lower absolute levels of body weight , fasting and 2 h plasma glucose and a healthier diet . Adherence to lifestyle changes during the intervention period predicted greater risk reduction during the total follow-up . Conclusions /interpretationLifestyle intervention in people at high risk of type 2 diabetes induces sustaining lifestyle change and results in long-term prevention of progression to type 2 diabetes . Trial registration Clinical Trials.gov NCT00518167 Funding The DPS study has been financially supported by the Academy of Finl and ( 128315 , 129330 ) , Ministry of Education , Novo Nordisk Foundation , Yrjö Jahnsson Foundation , Juho Vainio Foundation , Finnish Diabetes Research Foundation , Finnish Foundation for Cardiovascular Research , Unilever , and Competitive Research Funding from Tampere , Kuopio and Oulu University Hospitals . The study sponsors had no role in the design and conduct of the study ; the collection , analysis and interpretation of the data ; or the preparation , review or approval of the manuscript Aims /hypothesisThe aim of this study was to investigate the association of dietary macronutrient composition and energy density with the change in body weight and waist circumference and diabetes incidence in the Finnish Diabetes Prevention Study .Subjects and methods Overweight , middle-aged men ( n=172 ) and women ( n=350 ) with impaired glucose tolerance were r and omised to receive either ‘ st and ard care ’ ( control ) or intensive dietary and exercise counselling . Baseline and annual examinations included assessment of dietary intake with 3-day food records and diabetes status by repeated 75-g OGTTs . For these analyses the treatment groups were combined and only subjects with follow-up data ( n=500 ) were included . Results Individuals with low fat ( < median ) and high fibre ( > median ) intakes lost more weight compared with those consuming a high-fat ( > median ) , low-fibre ( < median ) diet ( 3.1 vs 0.7 kg after 3 years ) . In separate models , hazard ratios for diabetes incidence during a mean follow-up of 4.1 years were ( highest compared with lowest quartile ) 0.38 ( 95 % CI 0.19–0.77 ) for fibre intake , 2.14 ( 95 % CI 1.16–3.92 ) for fat intake , and 1.73 ( 95 % CI 0.89–3.38 ) for saturated-fat intake , after adjustment for sex , intervention assignment , weight and weight change , physical activity , baseline 2-h plasma glucose and intake of the nutrient being investigated . Compared with the low-fat/high-fibre category , hazard ratios were 1.98 ( 95 % CI 0.98–4.02 ) , 2.68 ( 95 % CI 1.40–5.10 ) , and 1.89 ( 95 % CI 1.09–3.30 ) for low-fat/low-fibre , high-fat/high-fibre , and high-fat/low-fibre , respectively . Conclusions /interpretationDietary fat and fibre intake are significant predictors of sustained weight reduction and progression to type 2 diabetes in high-risk subjects , even after adjustment for other risk factors Insulin resistance and beta-cell dysfunction , two factors central to the pathogenesis of type 2 diabetes , were studied in relation to the development of diabetes in a group of participants with impaired glucose tolerance in the Diabetes Prevention Program ( DPP ) at baseline and after specific interventions design ed to prevent diabetes . Participants were r and omly assigned to placebo ( n = 1,082 ) , metformin ( 850 mg twice a day ) ( n = 1,073 ) , or intensive lifestyle intervention ( n = 1,079 ) . The diabetes hazard rate was negatively associated with baseline insulin sensitivity ( hazard rate ratio = 0.62 - 0.94 per SD difference , depending on treatment group and measure of sensitivity ) and with baseline insulin secretion ( hazard rate ratio = 0.57 - 0.76 per SD ) . Improvements in insulin secretion and insulin sensitivity were associated with lower hazard rates in all treatment arms ( hazard rate ratio = 0.46 - 0.95 per SD increase and 0.29 - 0.79 per SD increase , respectively ) . In multivariate models that included the three metabolic variables ( changes in body weight , insulin sensitivity , and insulin secretion ) each significantly and independently predicted progression to diabetes when adjusted for the other two variables . The intensive lifestyle intervention , which elicited the greatest reduction in diabetes incidence , produced the greatest improvement in insulin sensitivity and the best preservation of beta-cell function after 1 year , whereas the placebo group , which had the highest diabetes incidence , had no significant change in insulin sensitivity and beta-cell function after 1 year . In the metformin group , diabetes risk , insulin sensitivity , and beta-cell function at 1 year were intermediate between those in the intensive lifestyle and placebo groups . In conclusion , higher insulin secretion and sensitivity at baseline and improvements in response to treatment were associated with lower diabetes risk in the DPP . The better preventive effectiveness of intensive lifestyle may be due to improved insulin sensitivity concomitant with preservation of beta-cell function 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 . OBJECTIVE The long-term impact of intentional weight loss on cardiovascular events remains unknown . We describe 12-month changes in body weight and cardiovascular risk factors in PREvención con DIeta MEDiterránea (PREDIMED)-Plus , a trial design ed to evaluate the long-term effectiveness of an intensive weight loss lifestyle intervention on primary cardiovascular prevention . RESEARCH DESIGN AND METHODS Overweight/obese adults with metabolic syndrome aged 55–75 years ( n = 626 ) were r and omized to an intensive weight loss lifestyle intervention based on an energy-restricted Mediterranean diet , physical activity promotion , and behavioral support ( IG ) or a control group ( CG ) . The primary and secondary outcomes were changes in weight and cardiovascular risk markers , respectively . RESULTS Diet and physical activity changes were in the expected direction , with significant improvements in IG versus CG . After 12 months , IG participants lost an average of 3.2 kg vs. 0.7 kg in the CG ( P < 0.001 ) , a mean difference of −2.5 kg ( 95 % CI −3.1 to −1.9 ) . Weight loss ≥5 % occurred in 33.7 % of IG participants compared with 11.9 % in the CG ( P < 0.001 ) . Compared with the CG , cardiovascular risk factors , including waist circumference , fasting glucose , triglycerides , and HDL cholesterol , significantly improved in IG participants ( P < 0.002 ) . Reductions in insulin resistance , HbA1c , and circulating levels of leptin , interleukin-18 , and MCP-1 were greater in IG than CG participants ( P < 0.05 ) . IG participants with prediabetes/diabetes significantly improved glycemic control and insulin sensitivity , along with triglycerides and HDL cholesterol levels compared with their CG counterparts . CONCLUSIONS PREDIMED-Plus intensive lifestyle intervention for 12 months was effective in decreasing adiposity and improving cardiovascular risk factors in overweight/obese older adults with metabolic syndrome , as well as in individuals with or at risk for diabetes BACKGROUND Findings from the Look AHEAD trial showed no significant reductions in the primary outcome of cardiovascular disease incidence in adults with type 2 diabetes r and omly assigned to an intensive lifestyle intervention for weight loss compared with those r and omly assigned to diabetes support and education ( control ) . We examined whether the incidence of cardiovascular disease in Look AHEAD varied by changes in weight or fitness . METHODS Look AHEAD was a r and omised clinical trial done at 16 clinical sites in the USA , recruiting patients from Aug 22 , 2001 , to April 30 , 2004 . In the trial , 5145 overweight or obese adults aged 45 - 76 years with type 2 diabetes were assigned ( 1:1 ) to an intensive lifestyle intervention or diabetes support and education . In this observational , post-hoc analysis , we examined the association of magnitude of weight loss and fitness change over the first year with incidence of cardiovascular disease . The primary outcome of the trial and of this analysis was a composite of death from cardiovascular causes , non-fatal acute myocardial infa rct ion , non-fatal stroke , or admission to hospital for angina . The secondary outcome included the same indices plus coronary artery bypass grafting , carotid endartectomy , percutaneous coronary intervention , hospitalisation for congestive heart failure , peripheral vascular disease , or total mortality . We adjusted analyses for baseline differences in weight or fitness , demographic characteristics , and risk factors for cardiovascular disease . The Look AHEAD trial is registered with Clinical Trials.gov , number NCT00017953 . FINDINGS For the analyses related to weight change , we excluded 311 ineligible participants , leaving a population of 4834 ; for the analyses related to fitness change , we excluded 739 participants , leaving a population of 4406 . In analyses of the full cohort ( ie , combining both study groups ) , over a median 10·2 years of follow-up ( IQR 9·5 - 10·7 ) , individuals who lost at least 10 % of their bodyweight in the first year of the study had a 21 % lower risk of the primary outcome ( adjusted hazard ratio [ HR ] 0·79 , 95 % CI 0·64 - 0·98 ; p=0·034 ) and a 24 % reduced risk of the secondary outcome ( adjusted HR 0·76 , 95 % CI 0·63 - 0·91 ; p=0·003 ) compared with individuals with stable weight or weight gain . Achieving an increase of at least 2 metabolic equivalents in fitness change was associated with a significant reduction in the secondary outcome ( adjusted HR 0·77 , 95 % CI 0·61 - 0·96 ; p=0·023 ) but not the primary outcome ( adjusted HR 0·78 , 0·60 - 1·03 ; p=0·079 ) . In analyses treating the control group as the reference group , participants in the intensive lifestyle intervention group who lost at least 10 % of their bodyweight had a 20 % lower risk of the primary outcome ( adjusted HR 0·80 , 95 % CI 0·65 - 0·99 ; p=0·039 ) , and a 21 % lower risk of the secondary outcome ( adjusted HR 0·79 , 95 % CI 0·66 - 0·95 ; p=0·011 ) ; however , change in fitness was not significantly associated with a change in the primary outcome . INTERPRETATION The results of this post-hoc analysis of Look AHEAD suggest an association between the magnitude of weight loss and incidence of cardiovascular disease in people with type 2 diabetes . These findings suggest a need to continue to refine approaches to identify individuals who are most likely to benefit from lifestyle interventions and to develop strategies to improve the magnitude of sustained weight loss with lifestyle interventions . FUNDING US National Institute of Diabetes and Digestive and Kidney Diseases The aim of the study was to find out whether participation in earlier intervention had an effect on the occurrence of retinopathy in study participants . We also examined risk factors ( age , sex , weight , fasting and 2 h glucose , fasting insulin , blood pressure , serum lipids ) for early retinal changes . The study included 522 individuals ( mean 55 years old , range 40–64 years ) with impaired glucose tolerance who were r and omized into intervention ( weight loss , healthy diet , and physical activity , N = 265 ) and control groups ( N = 257 ) . Intervention lasted for median of four years in 1993–2000 , after which annual follow-up visits at study clinics were conducted . In the years 2002–2006 ( at least five years after stopping intervention ) , fundus photography was offered for all study participants in four of five study clinics . Photographs were assessed by two experienced ophthalmologists ( A.A. and K.K. ) , masked for the group assignment . After exclusion of poor quality photographs , the data of 211 individuals ( N = 113 for intervention and N = 98 for control group ) were included in the present study . The occurrence of microaneurysms was significantly higher in the control ( 37/98 , 38 % ) than in the intervention group ( 27/113 , 24 % ; p = 0.029 ) . In the model , including age , sex , diabetes diagnosis before the retinal assessment , body mass index ( BMI ) , and treatment group , the odds ratio for microaneurysms was markedly lower in intervention group ( OR 0.52 ; 0.28–0.97 , p = 0.039 ) . The only risk factor that predicted the occurrence of microaneurysms was serum triglycerides at baseline ( mean ± SD 1.9 ± 0.9 vs. 1.6 ± 0.7 , mmol/L , with and without microaneurysms , respectively , p = 0.003 ) . Triglycerides associated with decreased microaneurysms in regression analysis for age , sex , fasting glucose , and intervention group ( OR 1.92 , p = 0.018 ) . Lifestyle intervention in overweight and obese individuals with impaired glucose tolerance showed decreased occurrence of retinal microaneurysms . Elevated serum triglycerides were associated to the development of early diabetic microangiopathy |
13,511 | 31,901,868 | Among the commonly reported findings , the genera of Bifidobacterium , Bacteroides , Faecalibacterium , Akkermansia and Roseburia were negatively associated with T2D , while the genera of Ruminococcus , Fusobacterium , and Blautia were positively associated with T2D . | A substantial body of literature has provided evidence for the role of gut microbiota in metabolic diseases including type 2 diabetes .
However , reports vary regarding the association of particular taxonomic groups with disease .
In this systematic review , we focused on the potential role of different bacterial taxa affecting diabetes . | Background Gut microbiota is now known to control glucose metabolism . Previous studies have shown that probiotics and prebiotics may improve glucose metabolism , but their effects have not been studied in combination with drug therapy . The aim of this study was to investigate whether probiotics and prebiotics combined with drug therapy affect diabetic outcomes . Methods Two different study design s were used to test gut microbiota modulating treatments with metformin ( MET ) or sitagliptin ( SITA ) in male C57Bl/6J mice . In Design 1 , diabetes was induced with four-week feeding with a ketogenic , 72 kcal% fat diet with virtually no carbohydrates . Mice were then r and omly divided into four groups ( n = 10 in each group ) : ( 1 ) vehicle , ( 2 ) Bifidobacterium animalis ssp . lactis 420 ( B420 ) ( 109 CFU/day ) , ( 3 ) MET ( 2 mg/mL in drinking water ) , or ( 4 ) MET + B420 ( same doses as in the MET and B420 groups ) . After another 4 weeks , glucose metabolism was assessed with a glucose tolerance test . Fasting glucose , fasting insulin and HOMA-IR were also assessed . In Design 2 , mice were fed the same 72 kcal% fat diet to induce diabetes , but they were simultaneously treated within their respective groups ( n = 8 in each group ) : ( 1 ) non-diabetic healthy control , ( 2 ) vehicle , ( 3 ) SITA [ 3 mg/(kg*day ) ] ( 4 ) SITA with prebiotic polydextrose ( PDX ) ( 0.25 g/day ) , ( 5 ) SITA with B420 ( 109 CFU/day ) , and ( 6 ) SITA + PDX + B420 . Glucose metabolism was assessed at 4 weeks , and weight development was monitored for 6 weeks . Results In Design 1 , with low-dose metformin , mice treated with B420 had a significantly lower glycemic response ( area under the curve ) ( factorial experiment , P = 0.002 ) and plasma glucose concentration ( P = 0.02 ) compared to mice not treated with B420 . In Design 2 , SITA + PDX reduced glycaemia in the oral glucose tolerance test significantly more than SITA only ( area under the curve reduced 28 % , P < 0.0001 ) . In addition , B420 , PDX or B420+PDX , together with SITA , further decreased fasting glucose concentrations compared to SITA only ( −19.5 , −40 and −49 % , respectively , P < 0.01 for each comparison ) . The effect of PDX may be due to its ability to increase portal vein GLP-1 concentrations together with SITA ( P = 0.0001 compared to vehicle ) whereas SITA alone had no statistically significant effect compared to vehicle ( P = 0.14 ) . Conclusions This study proposes that combining probiotics and /or prebiotics with antidiabetic drugs improves glycemic control and insulin sensitivity in mice . Mechanisms could be related to incretin secretion Background Recently , the relationship between gut microbiota and obesity has been highlighted . The present r and omized , double-blind , placebo-controlled study aim ed to evaluate the efficacy of transglucosidase ( TGD ) in modulating blood glucose levels and body weight gain in patients with type 2 diabetes mellitus ( T2DM ) and to clarify the underlying mechanism by analyzing the gut microbiota of T2DM patients . Methods This study included 60 patients who received placebo or TGD orally ( 300 or 900 mg/day ) for 12 weeks , and blood and fecal sample s were collected before and after 12 weeks . Comparisons of fecal bacterial communities were performed before and after the TGD treatment and were performed between T2DM patients and 10 healthy individuals , using the terminal-restriction fragment length polymorphism analysis . Results The Clostridium cluster IV and subcluster XIVa components were significantly decreased , whereas the Lactobacillales and Bifidobacterium population s significantly increased in the T2DM patients compared with the healthy individuals . By dendrogram analysis , most of the healthy individuals ( 6/10 ) and T2DM patients ( 45/60 ) were classified into cluster I , indicating no significant difference in fecal bacterial communities between the healthy individuals and the T2DM patients . In the placebo and TGD groups , the bacterial communities were generally similar before and after the treatment . However , after 12 weeks of TGD therapy , the Bacteroidetes-to-Firmicutes ratio in the TGD groups significantly increased and was significantly higher compared with that in the placebo group , indicating that TGD improved the growth of the fecal bacterial communities in the T2DM patients . Conclusions Therefore , TGD treatment decreased blood glucose levels and prevented body weight gain in the T2DM patients by inducing the production of oligosaccharides in the alimentary tract and modulating gut microbiota composition . Trial registration UMIN-CTR A high-fat diet ( HFD ) induces obesity and the associated increases in blood glucose and inflammation through changes in gut microbiota , endotoxemia , and increased gut permeability . To counteract this , research ers have suggested that the use of probiotics that suppress production of proinflammatory lipopolysaccharide ( LPS ) . Here , we tested whether Lactobacillus sakei OK67 , which inhibits gut microbiota LPS production selected from among the lactic acid bacteria isolated from kimchi , exerted antihypoglycemic or anti-inflammatory effects in HFD-fed mice . Mice were r and omly divided into 2 groups and fed an HFD or a low-fat diet for 4 weeks . These groups were further subdivided ; 1 subgroup was treated with L sakei OK67 and fed the experimental diet for 4.5 weeks , whereas the other subgroup was fed the experimental diet alone . L sakei OK67 treatment lowered HFD-elevated LPS levels in blood and colonic fluid and significantly decreased HFD-elevated fasting blood glucose levels and the area under the curve in an oral glucose tolerance test . L sakei OK67 treatment inhibited HFD-induced body and epididymal fat weight gains , suppressed HFD-induced tumor necrosis factor-α and interleukin-1β expression and nuclear factor-κB activation in the colon , and significantly increased HFD-suppressed interleukin-10 and tight junction protein expression in the colon . Oral administration of L sakei OK67 significantly downregulated HFD-induced expression of peroxisome proliferator-activated receptor γ , fatty acid synthase , and tumor necrosis factor-α in adipose tissue . In addition , L sakei OK67 treatment strongly inhibited nuclear factor-κB activation in LPS-stimulated peritoneal macrophages . We report that L sakei OK67 ameliorates HFD-induced hyperglycemia and obesity by reducing inflammation and increasing the expression of colon tight junction proteins in mice The purpose of the present study was to determine whether probiotic supplementation ( Lactobacillus casei Shirota ( LcS ) ) prevents diet-induced insulin resistance in human subjects . A total of seventeen healthy subjects were r and omised to either a probiotic ( n 8) or a control ( n 9 ) group . The probiotic group consumed a LcS-fermented milk drink twice daily for 4 weeks , whereas the control group received no supplementation . Subjects maintained their normal diet for the first 3 weeks of the study , after which they consumed a high-fat ( 65 % of energy ) , high-energy ( 50 % increase in energy intake ) diet for 7 d. Whole-body insulin sensitivity was assessed by an oral glucose tolerance test conducted before and after overfeeding . Body mass increased by 0·6 ( SE 0·2 ) kg in the control group ( P < 0·05 ) and by 0·3 ( SE 0·2 ) kg in the probiotic group ( P>0·05 ) . Fasting plasma glucose concentrations increased following 7 d of overeating ( control group : 5·3 ( SE 0·1 ) v. 5·6 ( SE 0·2 ) mmol/l before and after overfeeding , respectively , P < 0·05 ) , whereas fasting serum insulin concentrations were maintained in both groups . Glucose AUC values increased by 10 % ( from 817 ( SE 45 ) to 899 ( SE 39 ) mmol/l per 120 min , P < 0·05 ) and whole-body insulin sensitivity decreased by 27 % ( from 5·3 ( SE 1·4 ) to 3·9 ( SE 0·9 ) , P < 0·05 ) in the control group , whereas normal insulin sensitivity was maintained in the probiotic group ( 4·4 ( SE 0·8 ) and 4·5 ( SE 0·9 ) before and after overeating , respectively ( P>0·05 ) . These results suggest that probiotic supplementation may be useful in the prevention of diet-induced metabolic diseases such as type 2 diabetes Metformin is widely used in the treatment of type 2 diabetes ( T2D ) , but its mechanism of action is poorly defined . Recent evidence implicates the gut microbiota as a site of metformin action . In a double-blind study , we r and omized individuals with treatment-naive T2D to placebo or metformin for 4 months and showed that metformin had strong effects on the gut microbiome . These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial . Transfer of fecal sample s ( obtained before and 4 months after treatment ) from metformin-treated donors to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota . By directly investigating metformin – microbiota interactions in a gut simulator , we showed that metformin affected pathways with common biological functions in species from two different phyla , and many of the metformin-regulated genes in these species encoded metalloproteins or metal transporters . Our findings provide support for the notion that altered gut microbiota mediates some of metformin 's antidiabetic effects To our knowledge , no reports are available indicating the favorable effects of synbiotic bread consumption on blood lipid profiles among patients with type 2 diabetes mellitus ( T2DM ) . This study was conducted to evaluate the effects of the daily consumption of synbiotic bread on blood lipid profiles of patients with T2DM . This r and omized double-blinded controlled clinical trial was performed with 78 diabetic patients , aged 35–70 years . After a 2-week run-in period , subjects were r and omly assigned to consume either synbiotic ( n = 26 ) , probiotic ( n = 26 ) or control bread ( n = 26 ) for 8 weeks . The synbiotic bread contained viable and heat-resistant probiotic Lactobacillus sporogenes ( 1 × 108 CFU ) and 0.07 g inulin ( HPX ) as prebiotic per 1 g. The probiotic bread contained L. sporogenes ( 1 × 108 CFU ) per 1 g. Patients were asked to consume the synbiotic , probiotic and control breads three times a day in a 40 g package for a total of 120 g/day . Biochemical measurements including blood lipid profiles were conducted before and after 8 weeks of intervention . Consumption of the synbiotic bread , compared to the probiotic and control breads , led to a significant decrease in serum TAG ( P = 0.005 ) , VLDL-C ( P = 0.005 ) , TC/HDL-C ( P = 0.002 ) and a significant increase in serum HDL-C levels ( P = 0.01 ) . No significant effect of synbiotic bread consumption on FPG , TC , LDL-C and non-HDL-C levels was seen compared to the probiotic and control breads ( P > 0.05 ) . Trial registry code : http://www.i rct .ir I RCT 201311215623N13 Objective To investigate the functional effects of probiotic treatment on the gut microbiota , as well as liver and adipose gene expression in diet-induced obese mice . Design Male C57BL/6J mice were fed a high-fat diet ( HFD ) for 8 weeks to induce obesity , and then r and omized to receive HFD+probiotic ( Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 , n = 9 ) or HFD+placebo ( n = 9 ) for another 10 weeks . Normal diet ( ND ) fed mice ( n = 9 ) served as non-obese controls . Results Diet-induced obese mice treated with probiotics showed reduced body weight gain and fat accumulation as well as lowered plasma insulin , leptin , total-cholesterol and liver toxicity biomarkers . A total of 151,061 pyrosequencing reads for fecal microbiota were analyzed with a mean of 6,564 , 5,274 and 4,464 reads for the ND , HFD+placebo and HFD+probiotic groups , respectively . Gut microbiota species were shared among the experimental groups despite the different diets and treatments . The diversity of the gut microbiota and its composition were significantly altered in the diet-induced obese mice and after probiotic treatment . We observed concurrent transcriptional changes in adipose tissue and the liver . In adipose tissue , pro-inflammatory genes ( TNFα , IL6 , IL1β and MCP1 ) were down-regulated in mice receiving probiotic treatment . In the liver , fatty acid oxidation-related genes ( PGC1α , CPT1 , CPT2 and ACOX1 ) were up-regulated in mice receiving probiotic treatment . Conclusions The gut microbiota of diet-induced obese mice appears to be modulated in mice receiving probiotic treatment . Probiotic treatment might reduce diet-induced obesity and modulate genes associated with metabolism and inflammation in the liver and adipose tissue BACKGROUND The short-chain fatty acids formed in the human colon by the bacterial fermentation of fiber may have an antiinflammatory effect , may reduce insulin production , and may improve lipid metabolism . We previously showed in hypercholesterolemic patients that supplementation with the probiotic bacteria Lactobacillus plantarum 299v significantly lowers concentrations of LDL cholesterol and fibrinogen . OBJECTIVE We determined the influence of a functional food product containing L. plantarum 299v on lipid profiles , inflammatory markers , and monocyte function in heavy smokers . DESIGN Thirty-six healthy volunteers ( 18 women and 18 men ) aged 35 - 45 y participated in a controlled , r and omized , double-blind trial . The experimental group drank 400 mL/d of a rose-hip drink containing L. plantarum 299v ( 5 x 10(7 ) colony-forming units/mL ) ; the control group consumed the same volume of product without bacteria . The experiment lasted 6 wk and entailed no changes in lifestyle . RESULTS Significant decreases in systolic blood pressure ( P < 0.000 ) , leptin ( P < 0.000 ) , and fibrinogen ( P < 0.001 ) were recorded in the experimental group . No such changes were observed in the control group . Decreases in F(2)-isoprostanes ( 37 % ) and interleukin 6 ( 42 % ) were also noted in the experimental group in comparison with baseline . Monocytes isolated from subjects treated with L. plantarum showed significantly reduced adhesion ( P < 0.001 ) to native and stimulated human umbilical vein endothelial cells . CONCLUSION L. plantarum administration leads to a reduction in cardiovascular disease risk factors and could be useful as a protective agent in the primary prevention of atherosclerosis in smokers Background : The dramatic increase in the incidence of diabetes and its associated complications require a natural and safe solution to control and delay such complications . The present study tested the hypothesis that probiotics may affect biochemical indices of diabetic patients Methods : Thirty four types 2 diabetic patients aged between 25 to 65 years , and diagnosed with diabetes for less than 15 years were selected for this single- blinded clinical trial . Using balanced block r and om sampling , the patients were divided into two groups of intervention ( probiotics ) and placebo . Blood sample s tested for baseline glucose , insulin , TG , total cholesterol , LDL-C , HDL-C , malondialdehyde , high sensitive CRP ( hs-CRP ) and IL-6 . After six weeks of experiment , fasting blood sample s were re-tested and the data obtained were analyzed using SPSS software . Results : There were no significant differences between anthropometric data including body mass index and waist to hip ratio in placebo and treatment groups . There was no significant difference in FBS , Serum TG concentration total cholesterol and LDL-C levels between placebo and treatment groups . HDL-C levels were slightly elevated after probiotic treatment , which were not statistically significant . Insulin , MDA and IL-6 levels were reduced and high sensitive CRP hs . CRP levels were elevated , although , not statistically significant . Conclusion : The result of this study indicates a non- significant declining trend in the level of TG , MDA and IL-6 and insulin resistance after consumption of probiotics Objective The gut microbiota is known to be related to type 2 diabetes ( T2D ) , psychiatric conditions , and opioid use . In this study , we tested the hypothesis that variability in gut microbiota in T2D is associated with psycho-metabolic health . Methods A cross-sectional study was conducted among African American men ( AAM ) ( n = 99 ) that were out patients at a Chicago VA Medical Center . The main outcome measures included fecal microbiota ecology ( by 16S rRNA gene sequencing ) , psychiatric disorders including opioid use , and circulating leptin and oxytocin as representative hormone biomarkers for obesity and psychological pro-social behavior . Results The study subjects had prevalent overweight/obesity ( 78 % ) , T2D ( 50 % ) and co-morbid psychiatric ( 65 % ) and opioid use ( 45 % ) disorders . In the analysis of microbiota , the data showed interactions of opioids , T2D and metformin with Bifidobacterium and Prevotella genera . The differential analysis of Bifidobacterium stratified by opioids , T2D and metformin , showed significant interactions among these factors indicating that the effect of one factor was changed by the other ( FDR-adjusted p [ q ] < 0.01 ) . In addition , the pair-wise comparison showed that participants with T2D not taking metformin had a significant 6.74 log2 fold increase in Bifidobacterium in opioid users as compared to non-users ( q = 2.2 x 10−8 ) . Since metformin was not included in this pair-wise comparison , the significant ‘ q ’ suggested association of opioid use with Bifidobacterium abundance . The differences in Bifidobacterium abundance could possibly be explained by opioids acting as organic cation transporter 1 ( OCT1 ) inhibitors . Analysis stratified by lower and higher leptin and oxytocin ( divided by the 50th percentile ) in the subgroup without T2D showed lower Dialister in High-Leptin vs. Low-Leptin ( p = 0.03 ) . Contrary , the opposite was shown for oxytocin , higher Dialister in High-Oxytocin vs. Low-Oxytocin ( p = 0.04 ) . Conclusions The study demonstrated for the first time that Bifidobacterium and Prevotella abundance was affected by interactions of T2D , metformin and opioid use . Also , in subjects without T2D Dialister abundance varied according to circulating leptin and oxytocin BACKGROUND Probiotics have beneficial effect on obesity related disorders in animal models . Despite a large number of animal data , r and omized placebo-controlled trials ( RCT ) concluded that probiotics have a moderate effect on glycemic control-related parameters . However , effect of probiotics on insulin resistance are inconsistent . AIM In a double-blind single center RCT , effect of alive multistrain probiotic vs. placebo on insulin resistance in type 2 diabetes patient were assessed . METHODS A total of 53 patients met the criteria for inclusion . They were r and omly assigned to receive multiprobiotic " Symbiter " ( concentrated biomass of 14 probiotic bacteria genera Bifidobacterium , Lactobacillus , Lactococcus , Propionibacterium ) or placebo for 8-weeks administered as a sachet formulation . The primary main outcome was the change HOMA-IR ( homeostasis model assessment -estimated insulin resistance ) which calculated using Matthews et al. 's equation . Secondary outcomes were the changes in glycemic control-related parameters , anthropomorphic variables and cytokines . RESULTS Supplementation with alive multiprobiotic for 8 weeks was associated with significant reduction of HOMA-IR from 6.85 ± 0.76 to 5.13 ± 0.49 ( p = 0.047 ) , but remained static in the placebo group . With respect to our secondary outcomes , HbA1c insignificant decreased by 0.09 % ( p = 0.383 ) and 0.24 % ( p = 0.068 ) respectively in placebo and probiotics groups . However , in probiotic responders ( n = 22 , patient with decrease in HOMA-IR ) after supplementation a significant reduction in HbA1c by 0.39 % ( p = 0.022 ) as compared to non-responders was observed . In addition , from markers of chronic systemic inflammatory state only TNF-α and IL-1β changes significantly after treatment with probiotics . CONCLUSION Probiotic therapies modestly improved insulin resistance in patients with type 2 diabetes Background Lactobacillus gasseri BNR17 is a type of probiotic strain isolated from human breast milk . A study was reported regarding the fact that BNR17 was an inhibitor of obesity and diabetic activities in the human body through previous animal experiments . This study was furthered to investigate the effect of BNR17 , a probiotic strain isolated from human breast milk , on obese and overweight adults . Methods Sixty-two obese volunteers aged 19 to 60 with body mass index ≥ 23 kg/m2 and fasting blood sugar ≥ 100 mg/dL participated in a placebo controlled , r and omized , and double-blind trial . For 12 weeks , 57 participants were given either placebo or BNR17 and were tested by measuring body fat , body weight , various biochemical parameters , vital signs , and computed tomography at the start of the study and at weeks 4 , 8 , and 12 . The subjects assumed usual daily activities without having to make behavioral or dietary modifications during the course of the study . Results At the 12th week , a slight reduction in body weight was noted in the BNR17 group , but there were no significant weight changes between groups . Decrease of waist and hip circumferences in the BNR17 group was more pronounced than those in the placebo group . The two groups had no special or severe adverse reactions . Conclusion Despite there being no change in behavior or diet , administration of only the supplement of BNR17 reduced weight and waist and hip circumference . However , there were no significant differences between the two groups . These findings warrant a subsequent longer-term prospect i ve clinical investigation with a large population Background The consumption of foods containing probiotic and prebiotic ingredients is growing consistently every year , and in view of the limited number of studies investigating their effect in the elderly . Objective The objective of this study was to evaluate the effect of the consumption of a symbiotic shake containing Lactobacillus acidophilus , Bifidobacterium bifidum and fructooligosaccharides on glycemia and cholesterol levels in elderly people . Methods A r and omized , double-blind , placebo-controlled study was conducted on twenty volunteers ( ten for placebo group and ten for symbiotic group ) , aged 50 to 60 years . The criteria for inclusion in the study were : total cholesterol > 200 mg/dL ; triglycerides > 200 mg/dL and glycemia > 110 mg/dL. Over a total test period of 30 days , 10 individuals ( the symbiotic group ) consumed a daily dose of 200 mL of a symbiotic shake containing 108 UFC/mL Lactobacillus acidophilus , 108 UFC/mL Bifidobacterium bifidum and 2 g oligofructose , while 10 other volunteers ( the placebo group ) drank daily the same amount of a shake that did not contain any symbiotic bacteria . Blood sample s were collected 15 days prior to the start of the experiment and at 10-day intervals after the beginning of the shake intake . The st and ard lipid profile ( total cholesterol , triglycerides and HDL cholesterol ) and glycemia , or blood sugar levels , were evaluated by an enzyme colorimetric assay . Results The results of the symbiotic group showed a non-significant reduction ( P > 0.05 ) in total cholesterol and triglycerides , a significant increase ( P < 0.05 ) in HDL cholesterol and a significant reduction ( P < 0.05 ) in fasting glycemia . No significant changes were observed in the placebo group . Conclusion The consumption of symbiotic shake result ed in a significant increase in HDL and a significant decrease of glycemia . Trial Registration Clinical Trials.gov : The gut microbiota has been implicated in obesity and its progression towards metabolic disease . Dietary interventions that target the gut microbiota have been suggested to improve metabolic health . The aim of the present study was to investigate the effect of interventions with Lactobacillus paracasei F19 or flaxseed mucilage on the gut microbiota and metabolic risk markers in obesity . A total of fifty-eight obese postmenopausal women were r and omised to a single-blinded , parallel-group intervention of 6-week duration , with a daily intake of either L. paracasei F19 ( 9·4 × 1010 colony-forming units ) , flaxseed mucilage ( 10 g ) or placebo . Quantitative metagenomic analysis of faecal DNA was performed to identify the changes in the gut microbiota . Diet-induced changes in metabolic markers were explored using adjusted linear regression models . The intake of flaxseed mucilage over 6 weeks led to a reduction in serum C-peptide and insulin release during an oral glucose tolerance test ( P < 0·05 ) and improved insulin sensitivity measured by Matsuda index ( P < 0·05 ) . Comparison of gut microbiota composition at baseline and after 6 weeks of intervention with flaxseed mucilage showed alterations in abundance of thirty-three metagenomic species ( P < 0·01 ) , including decreased relative abundance of eight Faecalibacterium species . These changes in the microbiota could not explain the effect of flaxseed mucilage on insulin sensitivity . The intake of L. paracasei F19 did not modulate metabolic markers compared with placebo . In conclusion , flaxseed mucilage improves insulin sensitivity and alters the gut microbiota ; however , the improvement in insulin sensitivity was not mediated by the observed changes in relative abundance of bacterial species Introduction : The role of inflammatory cytokines in diabetes and its complications has been shown in some studies . The purpose of this study was to compare the effect of probiotic and conventional yogurt on inflammatory markers in patients with type 2 diabetes . Methods : Forty-four patients with type 2 diabetes were participated in this r and omized , double-blind controlled clinical trial and assigned to two intervention and control groups . The subjects in the intervention group consumed 300 g/d probiotic yogurt and subjects in the control group consumed 300 g/d conventional yogurt for 8 weeks . Anthropometric indices , dietary intakes , and serum levels of glucose , HbA1c , IL-6 , TNF-α and hs-CRP were evaluated at the beginning and end of the intervention . Results : For anthropometric indices and dietary intakes , no significant differences were seen within and between groups post intervention ( p > 0.05 ) . The consumption of probiotic yogurt caused significant decrease in HbA1c and TNF-α levels ( p= 0.032 and p= 0.040 , respectively ) in the intervention group . Conclusion : It is suggested that probiotic yogurt may be used as an alternative prevention approach and treatment method to control diabetic complications OBJECTIVE Ingestion of probiotics can modify gut microbiota and alter insulin resistance and diabetes development in rodents . We hypothesized that daily intake of Lactobacillus reuteri increases insulin sensitivity by changing cytokine release and insulin secretion via modulation of the release of glucagon-like peptides (GLP)-1 and -2 . RESEARCH DESIGN AND METHODS A prospect i ve , double-blind , r and omized trial was performed in 21 glucose-tolerant humans ( 11 lean : age 49 ± 7 years , BMI 23.6 ± 1.7 kg/m2 ; 10 obese : age 51 ± 7 years , BMI 35.5 ± 4.9 kg/m2 ) . Participants ingested 1010 b.i.d . L. reuteri SD5865 or placebo over 4 weeks . Oral glucose tolerance and isoglycemic glucose infusion tests were used to assess incretin effect and GLP-1 and GLP-2 secretion , and euglycemic-hyperinsulinemic clamps with [6,6 - 2H2]glucose were used to measure peripheral insulin sensitivity and endogenous glucose production . Muscle and hepatic lipid contents were assessed by 1H-magnetic resonance spectroscopy , and immune status , cytokines , and endotoxin were measured with specific assays . RESULTS In glucose-tolerant volunteers , daily administration of L. reuteri SD5865 increased glucose-stimulated GLP-1 and GLP-2 release by 76 % ( P < 0.01 ) and 43 % ( P < 0.01 ) , respectively , compared with placebo , along with 49 % higher insulin ( P < 0.05 ) and 55 % higher C-peptide secretion ( P < 0.05 ) . However , the intervention did not alter peripheral and hepatic insulin sensitivity , body mass , ectopic fat content , or circulating cytokines . CONCLUSIONS Enrichment of gut microbiota with L. reuteri increases insulin secretion , possibly due to augmented incretin release , but does not directly affect insulin sensitivity or body fat distribution . This suggests that oral ingestion of one specific strain may serve as a novel therapeutic approach to improve glucose-dependent insulin release The gut microbiota exerts a role in type 2 diabetes ( T2D ) , and deviations from a mutualistic ecosystem layout are considered a key environmental factor contributing to the disease . Thus , the possibility of improving metabolic control in T2D by correcting gut microbiome dysbioses through diet has been evaluated . Here , we explore the potential of two different energy-restricted dietary approaches – the fibre-rich macrobiotic Ma-Pi 2 diet or a control diet recommended by Italian professional societies for T2D treatment – to correct gut microbiota dysbioses in T2D patients . In a previous 21-d open-label MADIAB trial , fifty-six overweight T2D patients were r and omised to the Ma-Pi 2 or the control diet . For the present study , stools were collected before and after intervention from a subset of forty MADIAB participants , allowing us to characterise the gut microbiota by 16S rRNA sequencing and imputed metagenomics . To highlight microbiota dysbioses in T2D , the gut microbiota of thirteen normal-weight healthy controls were characterised . According to our findings , both diets were effective in modulating gut microbiome dysbioses in T2D , result ing in an increase of the ecosystem diversity and supporting the recovery of a balanced community of health-promoting SCFA producers , such as Faecalibacterium , Roseburia , Lachnospira , Bacteroides and Akkermansia . The Ma-Pi 2 diet , but not the control diet , was also effective in counteracting the increase of possible pro-inflammatory groups , such as Collinsella and Streptococcus , in the gut ecosystem , showing the potential to reverse pro-inflammatory dysbioses in T2D , and possibly explaining the greater efficacy in improving the metabolic control The gut microbiota is hypothesized to have a critical role in metabolic diseases , including type 2 diabetes ( T2D ) . A traditional Chinese herbal formula , Gegen Qinlian Decoction ( GQD ) , can alleviate T2D . To find out whether GQD modulates the composition of the gut microbiota during T2D treatment , 187 T2D patients were r and omly allocated to receive high ( HD , n=44 ) , moderate ( MD , n=52 ) , low dose GQD ( LD , n=50 ) or the placebo ( n=41 ) for 12 weeks in a double-blinded trial . Patients who received the HD or MD demonstrated significant reductions in adjusted mean changes from baseline of fasting blood glucose ( FBG ) and glycated hemoglobin ( HbA1c ) compared with the placebo and LD groups . Pyrosequencing of the V3 regions of 16S rRNA genes revealed a dose-dependent deviation of gut microbiota in response to GQD treatment . This deviation occurred before significant improvement of T2D symptoms was observed . Redundancy analysis identified 47 GQD-enriched species level phylotypes , 17 of which were negatively correlated with FBG and 9 with HbA1c . Real-time quantitative PCR confirmed that GQD significantly enriched Faecalibacterium prausnitzii , which was negatively correlated with FBG , HbA1c and 2-h postpr and ial blood glucose levels and positively correlated with homeostasis model assessment of β-cell function . Therefore , these data indicate that structural changes of gut microbiota are induced by Chinese herbal formula GQD . Specifically , GQD treatment may enrich the amounts of beneficial bacteria , such as Faecalibacterium spp . In conclusion , changes in the gut microbiota are associated with the anti-diabetic effects of GQD Background Gut lactobacilli can affect the metabolic functions of healthy humans . We tested whether a 1500 kcal/d diet supplemented with cheese containing the probiotic Lactobacillus plantarum TENSIA ( Deutsche Sammlung für Mikroorganismen , DSM 21380 ) could reduce some symptoms of metabolic syndrome in Russian adults with obesity and hypertension . Methods In this 3-week , r and omized , double-blind , placebo-controlled , parallel pilot study , 25 subjects ingested probiotic cheese and 15 ingested control cheese . Fifty grams of each cheese provided 175 kcal of energy . Blood pressure ( BP ) , anthropometric characteristics , markers of liver and kidney function , metabolic indices ( plasma glucose , lipids , and cholesterol ) , and urine polyamines were measured . Counts of fecal lactobacilli and L. plantarum TENSIA were evaluated using molecular methods . The data were analyzed by t-test for independent sample s and Spearman ’s partial correlation analysis . Results The probiotic L. plantarum TENSIA was present in variable amounts ( 529.6 ± 232.5 gene copies ) in 16/25 ( 64 % ) study subjects . Body mass index ( BMI ) was significantly reduced ( p = 0.031 ) in the probiotic cheese group versus the control cheese group . The changes in BMI were closely associated with the water content of the body ( r = 0.570 , p = 0.0007 ) when adjusted for sex and age . Higher values of intestinal lactobacilli after probiotic cheese consumption were associated with higher BMI ( r = 0.383 , p = 0.0305 ) and urinary putrescine content ( r = 0.475 , p = 0.006 ) . In patients simultaneously treated with BP-lowering drugs , similar reductions of BP were observed in both groups . A positive association was detected between TENSIA colonization and the extent of change of morning diastolic BP ( r = 0.617 , p = 0.0248 ) and a trend toward lower values of morning systolic BP ( r = −0.527 , p = 0.0640 ) at the end of the study after adjusting for BMI , age , and sex . Conclusion In a pilot study of obese hypertensive patients , a hypocaloric diet supplemented with a probiotic cheese helps to reduce BMI and arterial BP values , recognized symptoms of metabolic syndrome . Trial registration Current Controlled Trials IS RCT Background It is unclear whether specific gut microbiota is associated with remission of type 2 diabetes ( T2D ) after distinct types of bariatric surgery . Aims The aim of this study is to examine gut microbiota changes after laparoscopic Roux-en-Y gastric bypass ( RYGB ) or sleeve gastrectomy ( SG ) surgery in obese patients with T2D . Methods Whole-metagenome shotgun sequencing of DNA fragments using Illumina HiSeq2000 was obtained from stool sample s collected from 14 obese T2D patients pre-operatively ( while on very low calorie diet ) and 1 year after r and omisation to laparoscopic SG ( n = 7 ) or RYGB ( n = 7 ) . Result ing shotgun reads were annotated with Kyoto Encyclopedia of Genes and Genomes ( KEGG ) . Results Body weight reduction and dietary change was similar 1 year after both surgery types . Identical proportions ( n = 5/7 ) achieved diabetes remission ( HbA1c < 48 mmol/mol without medications ) 1 year after RYGB and SG . RYGB result ed in increased Firmicutes and Actinobacteria phyla but decreased Bacteroidetes phyla . SG result ed in increased Bacteroidetes phyla . Only an increase in Roseburia species was observed among those achieving diabetes remission , common to both surgery types . KEGG Orthology and pathway analysis predicted contrasting and greater gut microbiota metabolism changes after diabetes remission following RYGB than after SG . Those with persistent diabetes post-operatively had higher Desulfovibrio species pre-operatively . Conclusions Overall , RYGB produces greater and more predicted favourable changes in gut microbiota functional capacity than SG . An increase in Roseburia species was the only compositional change common to both types of surgery among those achieving diabetes remission OBJECTIVE Oxidative stress plays a major role in the pathogenesis and progression of diabetes . Among various functional foods with an antioxidant effect , probiotic foods have been reported to repress oxidative stress . The objective of this clinical trial was to assess the effects of probiotic and conventional yogurt on blood glucose and antioxidant status in type 2 diabetic patients . METHODS Sixty-four patients with type 2 diabetes mellitus , 30 to 60 y old , were assigned to two groups in this r and omized , double-blind , controlled clinical trial . The patients in the intervention group consumed 300 g/d of probiotic yogurt containing Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 and those in the control group consumed 300 g/d of conventional yogurt for 6 wk . Fasting blood sample s , 24-h dietary recalls , and anthropometric measurements were collected at the baseline and at the end of the trial . RESULTS Probiotic yogurt significantly decreased fasting blood glucose ( P < 0.01 ) and hemoglobin A1c ( P < 0.05 ) and increased erythrocyte superoxide dismutase and glutathione peroxidase activities and total antioxidant status ( P < 0.05 ) compared with the control group . In addition , the serum malondialdehyde concentration significantly decreased compared with the baseline value in both groups ( P < 0.05 ) . No significant changes from baseline were shown in insulin concentration and erythrocyte catalase activity within either group ( P > 0.05 ) . CONCLUSION The consumption of probiotic yogurt improved fasting blood glucose and antioxidant status in type 2 diabetic patients . These results suggest that probiotic yogurt is a promising agent for diabetes management OBJECTIVE To investigate the gut microbiota in healthy volunteers ( HVs ) , patients with overweight ( OW ) , and patients with obesity ( OB ) , including those with acanthosis nigricans ( AN ) or without AN ( N-AN ) . METHODS Microbial 16S rRNA genes were examined by using pyrosequencing technology and analyzed by using bioinformatics methods . RESULTS Subjects in the OW and OB groups showed severe disturbances in glycemic control , lipid profile , and inflammatory markers ( all P < 0.05 ) ; patients with AN had worse metabolic status ( P < 0.001 ) and a lower diversity of microbiota ( P < 0.05 ) . The OB and HV groups showed totally different gut microbiota composition . In the OB group , beneficial microbiotas including Bifidobacterium ( 0.01 % vs. 0.05 % , false discovery rate [ FDR ] = 4.27 * 10 - 5 ) , anti-inflammatory Faecalibacterium ( 6.70 % vs. 13.82 % , FDR = 0.010 ) , and butyrate-producing Ruminococcaceae were significantly decreased , whereas Bacillus ( 0.58 % vs. 0.04 % , FDR = 0.013 ) and potential opportunistic pathogens such as Fusobacterium ( 1.44 % vs. 0.11 % , FDR < 0.01 ) and Escherichia-Shigella ( 6.01 % vs. 0.76 % , FDR = 0.041 ) had outgrown dramatically . Function prediction revealed a significant increase in lipopolysaccharide bio synthesis proteins and bacterial invasion of epithelial cell-associated genes and a significant decrease in glucose and essential amino acid-related genes . CONCLUSIONS Gut microbiotas and their functions were significantly changed in obesity . More prospect i ve studies on association and causality between microbiota and obesity are imperative and might contribute to the prevention , diagnosis , and treatment of obesity The blood pressure-lowering effect of dairy products holds the potential to decrease the risk of cardiovascular disease ( CVD ) . An open question is if the successful expression of functional properties of the probiotic strain depends on host biomarkers and /or food matrix properties . The probiotic Lactobacillus plantarum strain TENSIA ® ( DSM 21380 ) is a novel microorganism with antimicrobial and antihypertensive functional properties . The aim of this study was to characterise the functional properties of the probiotic L. plantarum TENSIA and compare its effects on host anthropometric , clinical , and blood biomarkers when consumed with cheese or yoghurt . This study involved two double-blinded r and omised placebo-controlled exploratory trials ( IS RCT N15061552 and IS RCT N79645828 ) of healthy adults over a three-week period . The three-week consumption of probiotic L. plantarum TENSIA in a daily dose of 1 × 1010 cfu in probiotic cheese or a daily dose of 6 × 109 cfu in yoghurt with different content of carbohydrates , proteins , and lipids did not significantly change the body mass index ( BMI ) , plasma glucose and lipid levels , or inflammatory markers in the blood . Reduced lowered systolic and diastolic blood pressure values were detected , regardless of food matrix or baseline values for blood pressure and BMI . In conclusion , our study showed that three-week consumption of the probiotic L. plantarum TENSIA either in cheese or yoghurt lowered diastolic and systolic blood pressure regardless of food matrix and baseline values of blood pressure and BMI , confirming the impact of the functional properties of the probiotic strain in decreasing CVD risk Background / Objectives : Evidence from animal and in vitro models suggest a role of probiotic bacteria in improving glycaemic control and delaying the onset of type 2 diabetes . However , the evidence from controlled trials in humans is limited . The objective was to determine if the probiotic bacteria L. acidophilus La5 and B. animalis subsp lactis Bb12 , supplemented in a whole food ( yoghurt ) or isolated ( capsules ) form , can improve biomarkers of glycaemic control . Subjects/ methods : Following a 3-week washout period , 156 overweight men and women over 55 years ( mean age : 67±8 years ; mean body mass index ( 31±4 kg/m2 ) were r and omized to a 6-week double-blinded parallel study . The four intervention groups were : ( A ) probiotic yoghurt plus probiotic capsules ; ( B ) probiotic yoghurt plus placebo capsules ; ( C ) control milk plus probiotic capsules ; and ( D ) control milk plus placebo capsules . Outcome measurements , including fasting glucose , insulin , glycated haemoglobin and Homoeostasis Model Assessment of Insulin Resistance ( HOMA-IR ) , were performed at baseline and week 6 . Results : Relative to the milk-control group , probiotic yoghurt result ed in a significantly higher HOMA-IR ( 0.32±0.15 , P=0.038 ) , but did not have a significant effect on the other three measures of glycaemic control ( P>0.05 ) . Relative to placebo capsules , probiotic capsules result ed in a significantly higher fasting glucose ( 0.15±0.07 mmol/l , P=0.037 ) , with no significant effect on the other three measures of glycaemic control ( P>0.05 ) . Further analyses did not identify other variables as contributing to these adverse findings . Conclusions : Data from this study does not support the hypothesis that L. acidophilus La5 and B. animalis subsp lactis Bb12 , either in isolated form or as part of a whole food , benefit short-term glycaemic control . Indeed , there is weak data for an adverse effect of these strains on glucose homoeostasis A significant number of human clinical trials have reported no adverse effects associated with consumption of Lactobacillus reuteri ( L. reuteri ) . In the present study , the clinical safety and toxicology of oral ingestion of supplement capsules containing L. reuteri NCIMB 30242 was investigated . A r and omized group of 131 subjects received a dose of 2.9 × 10⁹ CFU L. reuteri NCIMB 30242 capsules ( n=67 ) or placebo capsules ( n=64 ) twice daily for 9 weeks . Clinical chemistry and hematological parameters of safety were analyzed . The frequency , duration and intensity of adverse events (AE)s and clinical significance of safety parameters were recorded for both groups . No clinical ly significant differences between the probiotic capsule and placebo capsule treated groups were detected in either the blood clinical chemistry or hematology results . The frequency and intensity of AEs was similar in the two groups . These results demonstrate that administration of a twice daily dose of 2.9 × 10⁹ CFU was safe and well tolerated in the population evaluated over 9 weeks Aberrant microbiota composition and function have been linked to several pathologies , including type 2 diabetes . In animal models , prebiotics induce favourable changes in the intestinal microbiota , intestinal permeability ( IP ) and endotoxaemia , which are linked to concurrent improvement in glucose tolerance . This is the first study to investigate the link between IP , glucose tolerance and intestinal bacteria in human type 2 diabetes . In all , twenty-nine men with well-controlled type 2 diabetes were r and omised to a prebiotic ( galacto-oligosaccharide mixture ) or placebo ( maltodextrin ) supplement ( 5·5 g/d for 12 weeks ) . Intestinal microbial community structure , IP , endotoxaemia , inflammatory markers and glucose tolerance were assessed at baseline and post intervention . IP was estimated by the urinary recovery of oral 51Cr-EDTA and glucose tolerance by insulin-modified intravenous glucose tolerance test . Intestinal microbial community analysis was performed by high-throughput next-generation sequencing of 16S rRNA amplicons and quantitative PCR . Prebiotic fibre supplementation had no significant effects on clinical outcomes or bacterial abundances compared with placebo ; however , changes in the bacterial family Veillonellaceae correlated inversely with changes in glucose response and IL-6 levels ( r -0·90 , P=0·042 for both ) following prebiotic intake . The absence of significant changes to the microbial community structure at a prebiotic dosage/length of supplementation shown to be effective in healthy individuals is an important finding . We propose that concurrent metformin treatment and the high heterogeneity of human type 2 diabetes may have played a significant role . The current study does not provide evidence for the role of prebiotics in the treatment of type 2 diabetes Abstract Aims / Introduction To evaluate the effect of probiotic supplements on insulin resistance in pregnant women with diet‐controlled gestational diabetes mellitus . Material s and Methods A r and omized , double‐blind , placebo‐controlled trial was carried out between June 2016 and February 2017 . Pregnant women with diet‐controlled gestational diabetes mellitus were enrolled in the study at 24–28 weeks‐of‐gestation and r and omized to receive either probiotic supplements containing Bifidobacterium and Lactobacillus or a placebo daily for four consecutive weeks . Primary outcomes were mean differences in insulin resistance ( homeostatic model assessment for insulin resistance ) , fasting insulin and fasting plasma glucose between the two groups . Secondary outcomes were changes in maternal weight after the intervention . Results Data from 28 patients in the probiotic group and 29 in the placebo group were analyzed . The changes in metabolic parameters after r and omization showed significant improvement in glucose metabolism in the probiotic group compared with the placebo group , including fasting plasma glucose ( 0.68 ± 5.88 vs 4.620 ± 7.78 mg/dL , mean difference −3.94 mg/dL , 95 % confidence interval −7.62 , −0.27 , P = 0.034 ) , fasting plasma insulin ( 1.11 ± 1.71 vs 3.77 ± 1.70 mIU/L , mean difference −2.67 mIU/L , 95 % confidence interval −3.57 , −1.76 , P = 0.001 ) and homeostatic model assessment for insulin resistance ( 0.25 ± 0.37 vs 0.89 ± 0.46 , mean difference −0.63 , 95 % confidence interval −0.86 , −0.41 , P = 0.001 ) . Weight gain during r and omization was similar between the two groups . Conclusions Four weeks of probiotic supplements in women with diet‐controlled gestational diabetes in the late second and early third trimester lowered fasting glucose and increased insulin sensitivity . Probiotic supplements may be considered as an adjunct treatment for glycemic control in these patients Probiotic therapies are going to be an effective alternative therapeutic strategy in the treatment and management of diabetes . The mechanism behind the essential effects of probiotic therapies in diabetic patients was not fully understood . The objective of this study was to evaluate the effects of probiotic soy milk containing Lactobacillus planetarum A7 on inflammation , lipid profile , fasting blood glucose , and serum adiponectin among patients with type 2 diabetes mellitus . Forty patients with type 2 diabetes , at the age of 35–68 years old , were assigned to two groups in this r and omized , double-blind , controlled clinical trial . The patients in the intervention group consumed 200 ml/day of probiotic soy milk containing L. planetarum A7 and those in control group consumed 200 ml/day of pure soy milk for 8 weeks . Serum TNF-α , C reactive protein , adiponectin , lipid profile , and fasting blood glucose were determined before and after intervention . In intervention group , serum adiponectin in pre- and post-treatment did not show any significant changes ( 2.52 ± 0.74 vs 2.84 ± 0.61 , P = 0.658 ) , as well as changes in serum TNF-α and C reactive protein ( 172.44 ± 5.7 vs 172.83 ± 7.6 , P = 0.278 , 4.2 ± 1.4 vs 4.5 ± 1.9 , P = 0.765 , respectively ) . Low-density cholesterol and high-density cholesterol changed significantly ( P = 0.023 , P = 0.017 , respectively ) , but fasting blood glucose did not show any significant changes . The results of this study showed that consumption of probiotic soy milk and soy milk has no effect on serum adiponectin and inflammation , but it can change lipid profile among type 2 diabetic patients Our primary objective was to determine whether administering the viscous and fermentable polysaccharide PolyGlycopleX ( PGX ) with metformin ( MET ) or sitagliptin/metformin ( S/MET ) reduces hyperglycemia in Zucker diabetic fatty ( ZDF ) rats more so than monotherapy of each . Glucose tolerance , adiposity , satiety hormones and mechanisms related to dipeptidyl peptidase 4 activity , gut microbiota and , hepatic and pancreatic histology were examined . Male ZDF rats ( 9 - 10 weeks of age ) were r and omized to : i ) cellulose/vehicle ( control , C ) ; ii ) PGX ( 5 % wt/wt)/vehicle ( PGX ) ; iii ) cellulose/metformin ( 200 mg/kg ) ( MET ) ; iv ) cellulose/S/MET ( 10 mg/kg+200 mg/kg ) ( S/MET ) ; v ) PGX (5%)+MET ( 200 mg/kg ) ( PGX+MET ) ; vi ) cellulose/sitagliptin/MET (5%)+(10 mg/kg+200 mg/kg ) ( PGX+S/MET ) for 6 weeks . PGX+MET and PGX+S/MET reduced glycemia compared with C and singular treatments ( P=0.001 ) . Weekly fasted and fed blood glucose levels were lower in PGX+MET and PGX+S/MET compared with all other groups at weeks 4 , 5 , and 6 ( P=0.001 ) . HbA1c was lower in PGX+S/MET than C , MET , S/MET , and PGX at week 6 ( P=0.001 ) . Fat mass was lower and GLP1 was higher in PGX+S/MET compared with all other groups ( P=0.001 ) . β-cell mass was highest and islet degeneration lowest in PGX+S/MET . Hepatic lipidosis was significantly lower in PGX+S/MET compared with PGX or S/MET alone . When combined with PGX , both MET and S/MET markedly reduce glycemia ; however , PGX+S/MET appears advantageous over PGX+MET in terms of increased β-cell mass and reduced adiposity . Both combination treatments attenuated diabetes in the obese Zucker rat ABSTRACT Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus ( T2DM ) . With a r and omized clinical trial , we tested the hypothesis that alteration of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically design ed herbal formula ( AMC ) . Four hundred fifty patients with T2DM and hyperlipidemia were r and omly assigned to either the metformin- or AMC-treated group . After 12 weeks of treatment , 100 patients were r and omly selected from each group and assessed for clinical improvement . The effects of the two drugs on the intestinal microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods . Both metformin and AMC significantly alleviated hyperglycemia and hyperlipidemia and shifted gut microbiota structure in diabetic patients . They significantly increased a coabundant group represented by Blautia spp . , which significantly correlated with the improvements in glucose and lipid homeostasis . However , AMC showed better efficacies in improving homeostasis model assessment of insulin resistance ( HOMA-IR ) and plasma triglyceride and also exerted a larger effect on gut microbiota . Furthermore , only AMC increased the coabundant group represented by Faecalibacterium spp . , which was previously reported to be associated with the alleviation of T2DM in a r and omized clinical trial . Metformin and the Chinese herbal formula may ameliorate type 2 diabetes with hyperlipidemia via enriching beneficial bacteria , such as Blautia and Faecalibacterium spp . IMPORTANCE Metabolic diseases such as T2DM and obesity have become a worldwide public health threat . Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases , and thus the gut microbiota serves as a promising target for disease control . In this study , we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs : metformin and a specifically design ed Chinese herbal formula ( AMC ) for diabetic patients with hyperlipidemia . Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota . Blautia spp . were identified as being associated with improvements in glucose and lipid homeostasis for both drugs . AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels , which were associated with the enrichment of Faecalibacterium spp . In brief , these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula . Metabolic diseases such as T2DM and obesity have become a worldwide public health threat . Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases , and thus the gut microbiota serves as a promising target for disease control . In this study , we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs : metformin and a specifically design ed Chinese herbal formula ( AMC ) for diabetic patients with hyperlipidemia . Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota . Blautia spp . were identified as being associated with improvements in glucose and lipid homeostasis for both drugs . AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels , which were associated with the enrichment of Faecalibacterium spp . In brief , these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula Probiotics have been reported to ameliorate symptoms of type 2 diabetes mellitus ( T2DM ) in animal models and human studies . We previously demonstrated that oral administration of Lactobacillus reuteri ADR-3 reduced insulin resistance in high-fructose-fed ( HFD ) rats . In the present study , we first identified another L. reuteri strain , ADR-1 , which displayed anti-diabetes activity that reduced the levels of serum HbA1c and cholesterol and that increased antioxidant proteins in HFD rats . We further performed a r and omized , double-blinded , placebo-controlled trial with a total of 68 T2DM patients to examine the beneficial effects of oral consumption of L. reuteri strains ADR-1 and ADR-3 and to investigate the associated changes in intestinal flora using a quantitative PCR method to analyze 16 S rRNA in fecal specimens . Significant reductions in HbA1c and serum cholesterol were observed in participants in the live ADR-1 consumption group ( n = 22 ) after 3 months of intake when compared with those in the placebo group ( n = 22 ) . Although there was no significant difference in the HbA1c serum level among participants who consumed heat-killed ADR-3 ( n = 24 ) , the systolic blood pressure and mean blood pressure were significantly decreased after 6 months of intake . There was no obvious change in serum inflammatory cytokines or antioxidant proteins in participants after intaking ADR-1 or ADR-3 , except for a reduction in IL-1β in the ADR-3 consumption group after 6 months of intake . With the analysis of fecal microflora , we found that L. reuteri or Bifidobacterium spp . were significantly increased in the ADR-1 and ADR-3 consumption groups , respectively , after 6 months of intake . Interestingly , a significant reduction in HbA1c was observed in the ADR-1 and ADR-3 consumption participants who displayed at least an 8-fold increase in fecal L. reuteri . We also observed that there was a significantly positive correlation between Bifidobacterium spp . and Lactobacillus spp . in participants with increased levels of fecal L. reuteri . In the ADR-1 intake group , the fecal Lactobacillus spp . level displayed a positive correlation with Bifidobacterium spp . but was negatively correlated with Bacteroidetes . The total level of fecal L. reuteri in participants in the ADR-3 consumption group was positively correlated with Firmicutes . In conclusion , L. reuteri strains ADR-1 and ADR-3 have beneficial effects on T2DM patients , and the consumption of different strains of L. reuteri may influence changes in intestinal flora , which may lead to different outcomes after probiotic intake |
13,512 | 32,180,364 | This systematic review comparing long‐term outcomes after cruciate ligament reconstruction with either autograft or synthetics suggests no significant differences in failure risk .
Autografts were inferior to synthetics with respect to restoring knee joint stability and patient‐reported outcome scores , and were also associated with more postoperative complications | To describe the outcomes of autografts and synthetics in anterior cruciate ligament ( ACL ) and posterior cruciate ligament ( PCL ) reconstruction with respect to instrumented laxity measurements , patient‐reported outcome scores , complications , and graft failure risk . | Background : The optimal graft choice of anterior cruciate ligament ( ACL ) reconstruction remains controversial . Purpose : To compare the outcomes , especially the long-term cumulative failure rate , of ACL reconstruction using either synthetics with remnant preservation or hamstring autografts ( 4-str and semitendinosus and gracilis tendons ) . Study Design : Cohort study ; Level of evidence , 2 . Methods : A total of 133 patients who underwent ACL reconstruction ( synthetics : n = 43 ; hamstring autografts : n = 90 ) between July 2004 and December 2007 were included . Question naires ( Tegner activity scale , Lysholm knee scale , and International Knee Documentation Committee [ IKDC ] subjective form ) were completed preoperatively and at 6 months , 1 year , 5 years , and 10 years postoperatively . The Knee injury and Osteoarthritis Outcome Score ( KOOS ) was additionally applied at 10 years ’ follow-up . The physical examination was based on the 2000 IKDC form . The manual maximum side-to-side difference ( KT-1000 arthrometer ) , single-hop test , thigh muscle atrophy , and joint degeneration ( Kellgren and Lawrence classification ) were evaluated . The Kaplan-Meier curve and log-rank test ( Mantel-Cox , 95 % CI ) were used to compare graft survivorship . Results : Ten years postoperatively , 111 patients were available , with 38 ( 88.4 % ) patients ( mean age , 27.6 ± 9.3 years ; 28 men ) with synthetics and 73 ( 81.1 % ) patients ( mean age , 28.6 ± 8.8 years ; 64 men ) with hamstring autografts . Among them , 104 patients ( synthetics : n = 35 [ 81.4 % ] ; hamstring autografts : n = 69 [ 76.7 % ] ) completed subjective evaluations , and 89 patients ( synthetics : n = 30 [ 69.8 % ] ; hamstring autografts : n = 59 [ 65.6 % ] ) completed objective evaluations . For hamstring autografts and synthetics , the cumulative failure rates were 8.2 % and 7.9 % , respectively , and the log-rank test demonstrated no significant difference between the 2 Kaplan-Meier survival curves ( P = .910 ) . At 6 months postoperatively , for hamstring autografts and synthetics , the mean Lysholm score was 83.0 ± 7.8 and 88.1 ± 7.5 , respectively ( P < .001 ) ; the mean IKDC score was 83.8 ± 7.8 and 86.9 ± 4.5 , respectively ( P = .036 ) ; and the mean Tegner score was 3.7 ± 1.1 and 5.0 ± 1.5 , respectively ( P < .001 ) . At 1 year postoperatively , the mean Tegner score was 5.5 ± 1.9 and 6.5 ± 2.0 , respectively ( P = .011 ) . No statistically significant difference was observed on other subjective evaluation findings , physical examination findings ( overall IKDC grade A : 45.8 % of hamstring autografts , 50.0 % of synthetics ) , side-to-side difference ( 1.5 ± 1.5 mm for synthetics , 2.4 ± 2.1 mm for hamstring autografts ) , single-hop test findings ( grade A : 84.7 % of hamstring autografts , 93.3 % of synthetics ) , grade A/B thigh muscle atrophy ( 88.1 % of hamstring autografts , 93.3 % of synthetics ) , ipsilateral radiographic osteoarthritis ( 55.9 % of hamstring autografts , 50.0 % of synthetics ) , and graft survivorship . Conclusion : In this prospect i ve cohort study , primary ACL reconstruction using either synthetics with remnant preservation or hamstring autografts showed satisfactory outcomes , especially the long-term cumulative failure rate , at 10 years postoperatively . Patient-reported outcomes suggested that symptom relief and restoration of function might occur earlier in those with synthetics Background Injury to the anterior cruciate ligament ( ACL ) of the knee is common . Following complete rupture of the ACL , insufficient re-vascularization of the ligament prevents it from healing completely , creating a need for reconstruction . A variety of grafts are available for use in ACL reconstruction surgery , including synthetic grafts . Over the last two decades new types of synthetic ligaments have been developed . One of these synthetic ligaments , the Ligament Advanced Reinforcement System ( LARS ) , has recently gained popularity . The aim of this systematic review was to assess the current best available evidence for the effectiveness of the LARS as a surgical option for symptomatic , anterior cruciate ligament rupture in terms of graft stability , rehabilitation time and return to pre-injury function . Method This systematic review included studies using subjects with symptomatic , ACL ruptures undergoing LARS reconstruction . A range of electronic data bases were search ed in May 2010 . The method ological quality of studies was appraised with a modified version of the Law critical appraisal tool . Data relating to study characteristics , surgical times , complication rates , outcomes related to knee stability , quality of life , function , and return to sport as well as details of rehabilitation programs and timeframes were collected . Results This review identified four studies of various design s , of a moderate method ological quality . Only one case of knee synovitis was reported . Patient satisfaction with LARS was high . Graft stability outcomes were found to be inconsistent both at post operative and at follow up periods . The time frames of rehabilitation periods were poorly reported and at times omitted . Return to pre-injury function and activity was often discussed but not reported in results . Conclusions There is an emerging body of evidence for LARS with comparable complication rates to traditional surgical techniques , and high patient satisfaction scores . However , this systematic review has highlighted several important gaps in the existing literature that require future prospect i ve investigation . The findings of this review were equivocal with regards to other measures such as graft stability and long term functional outcomes . While the importance of rehabilitation following LARS is well recognised , there is limited evidence to guide rehabilitation protocol We have undertaken a r and omised clinical trial comparing two methods of reconstruction of the anterior cruciate ligament in patients with chronic instability . We used an ipsilateral bone-patellar-tendon-bone autograft in 27 patients and the Ligament Advancement Reinforcement System ( LARS ) artificial ligament in 26 . Assessment before and at two , six , 12 and 24 months after surgery , included the history , physical examination , a modified International Knee Documentation Committee ( IKDC ) score , the Tegner score , the Knee Injury and Osteoarthritis Outcome Score ( KOOS ) and instrumented laxity testing . There were no cases of reactive synovitis or of infection of the knee , and there was no difference regarding the failure rate between the two groups . The IKDC showed no significant differences between the two groups at any stage of the follow-up . The KOOS evaluation showed consistently better results in all subscales for the LARS group during the first year of follow-up . After 24 months these differences were no longer evident . Instrument-tested laxity was greater in the LARS group at all stages of follow-up , but the differences were not significant at 24 months . Our findings suggest that at follow-up at 24 months the LARS ligament seems to be a satisfactory treatment option , especially when an early return to high levels of activity is dem and ed Purpose Several studies compare the short- and long-term results of anterior cruciate ligament ( ACL ) reconstruction using bone-patellar tendon-bone ( BPTB ) graft or double-looped semitendinosus and gracilis ( DLSG ) graft . However , no studies evaluate the long-term results of BPTB grafts fixed with metal interference screws and DLSG grafts fixed with the Bone Mulch Screw and the Washer Loc . This prospect i ve r and omized multicentre study has the null hypothesis that there is no difference in long-term outcome between the two procedures . Methods A total of 114 patients with a symptomatic ACL rupture were r and omized to reconstruction with either a BPTB graft ( N = 58 ) or a DLSG graft ( N = 56 ) . Follow-up was conducted after one , two and seven years . At the seven-year follow-up , 102 of the 114 patients ( 89 % ) were available for evaluation ; however , 16 of these by telephone-interview only . Results Ten patients in the BPTB group and 19 patients in the DLSG group underwent additional knee surgery ( P = 0.048 ) , two and three , respectively , of these were ACL revisions ( n.s . ) . The total flexion work was lower in the DLSG group ( P = 0.001 ) . The mean peak flexion torque and extension work , however , showed no difference between the groups . No significant differences were found between the groups regarding the Tegner activity score , the Lysholm functional score , the Knee injury and osteoarthritis outcome score ( KOOS ) , subjective knee function , anterior knee pain or mobility . There was no significant difference in laxity between the groups on the Lachman test or the KT-1,000 maximum manual force test . Conclusions Both grafts and fixation methods result ed in satisfactory subjective outcome and objective stability . Both these methods can therefore be considered as suitable alternatives for ACL reconstructions . Level of evidence II Background : Because of specific method ological difficulties in conducting r and omized trials , surgical research remains dependent predominantly on observational or non‐r and omized studies . Few vali date d instruments are available to determine the method ological quality of such studies either from the reader 's perspective or for the purpose of meta‐ analysis . The aim of the present study was to develop and vali date such an instrument OBJECTIVE To compare the therapeutic effect of anterior cruciate ligament ( ACL ) reconstruction by means of four-str and semitendinosus tendon autograft and ligament advanced reinforcement system ( LARS ) by arthroscopy . METHODS From July 2002 to April 2005 , 42 patients underwent ACL reconstruction by arthroscopy . Twenty-seven patients were treated by four-str and semitendinosus tendon autograft ( semitendinosus tendon autograft group ) , including 22 males and 5 females , with the age from 20 years to 52 years . Among these patients , there were 12 sports injuries , 8 traffic accidents and 7 other injuries . There were 16 cases of left knees and 11 of right knees . The pre-operation Lysholm score was 50.70 + /- 6.68 , and the course of the disease was 2 to 12 months . Other 15 patients were treated by LARS artificial ligament ( LARS group ) , including 12 males and 3 females , with the age from 17 years to 40 years . Among these patients , there were 8 sports injuries , 4 traffic accidents and 3 other injuries . There were 6 cases of left knees and 9 of right knees . The pre-operation Lysholm score was 50.20 + /- 6.22 , and the course of the disease was 3 to 12 months . There was no statistically significant difference between the two groups ( P > 0.05 ) . The ranges of motion , stability and complication of the knee were evaluated during the follow-up . RESULTS All incisions healed at the first stage . The patients in the semitendinosus tendon autograft group were followed up for 22 months to 43 months , while 18 months to 40 months in the LARS group . There were 5 patients ( 19 % ) whose tensile gap was more than 3 mm when the max tensile force text was done in the semitendinosus tendon autograft group , and 3 patients ( 20 % ) in the LARS group . The Lysholm score was 87.80 + /- 3.41 in the semitendinosus tendon autograft autograft group , and 88.90 + /- 3.30 in the LARS group . There was no statistically significant difference between the two groups ( P > 0.05 ) . The final evaluation based on the improved Lysholm classification st and ard showed the choiceness rate was 92.6 % ( 18 excellent cases , 7 good cases and 2 fair cases ) in the semitendinosus tendon autograft group , and 93.3 % ( 11 excellent cases , 3 good cases , 1 fair case ) in the LARS group . There was no statistically significant difference between the two groups ( P > 0.05 ) . The joint motion capability evaluation , according to the Tegner st and ard , showed 3 to 6 class ( with the average class of 4.93 ) in the semitendinosus tendon autograft group , and 3 to 7 class ( with the average class of 5.03 ) in the LARS group . There was no statistically significant difference ( P > 0.05 ) . The knee extension in 2 cases was 5 degrees less than the normal , and in 5 cases 5 - 10 degrees less than the normal in the semitendinosus tendon autograft group . But in all cases in the LARS group , joint motion recovered to the normal ( P < 0.05 ) . There was no sign of synovitis in both groups . CONCLUSION The recent clinical result of ACL reconstruction with the four-str and semitendinosus tendon autograft or LARS artificial ligament by arthroscopy is satisfactory without significant difference . LARS can shorten the recovery time without complications such as synovitis in 2-year follow-up |
13,513 | 17,054,245 | This review does not currently provide any strong evidence on the relative effectiveness of interventions to treat Burkitt 's lymphoma . | BACKGROUND Burkitt 's lymphoma ( BL ) is a small non-cleaved cell lymphoma which commonly presents as jaw swellings .
Uncertainty remains as to the most effective form of management .
OBJECTIVES To assess the evidence of any therapeutic strategy in the treatment of BL . | A r and omized clinical trial design ed to compare the effectiveness of cytoxan ( CTX ) alone versus a combination consisting of CTX , vincristine ( Oncovin ) and methotrexate ( COM ) in the treatment of Burkitt 's lymphoma ( BL ) was carried out . Nineteen patients were selected at r and om to receive CTX alone while 21 received COM . The two treatment regimens were equally effective in inducing remissions , and complete response rates of 83.3 % and 84.3 % were observed for CTX- and COM-treated patients , respectively . The relapse frequencies were also equal but the pattern of relapse was clearly different . Seven out of 8 ( 87.5 % ) in the CTX group relapsed with systemic and central nervous system ( CNS ) tumor , while 8 out of 10 ( 80 % ) in the COM group relapsed with CNS disease only . This difference is highly significant p = 0.008 . The remission duration s and survival to date are the same The combination of cyclophosphamide , doxorubicin , vincristine , and prednisone , given every 3 weeks ( CHOP-21 ) is st and ard chemotherapy for aggressive lymphomas . To determine whether CHOP given every 2 weeks ( CHOP-14 ) or the addition of etoposide ( CHOEP-21 , CHOEP-14 ) can improve results in patients ages 18 to 60 years with good prognosis ( normal lactic dehydrogenase [ LDH ] level ) , 710 patients were r and omized to 6 cycles of CHOP-21 , CHOP-14 , CHOEP-21 ( CHOP plus etoposide 100 mg/m2 days 1 - 3 ) , or CHOEP-14 in a 2 x 2 factorial study design . Patients in the biweekly regimens received granulocyte colony-stimulating factor ( G-CSF ) starting from day 4 . Patients received radiotherapy ( 36 Gy ) to sites of initial bulky disease and extranodal disease . CHOEP achieved better complete remission ( 87.6 % versus 79.4 % ; P = .003 ) and 5-year event-free survival rates ( 69.2 % versus 57.6 % ; P = .004 , primary end point ) than CHOP , whereas interval reduction improved overall survival ( P = .05 ; P = .044 in the multivariate analysis ) . Although the CHOEP regimens induced more myelosuppression , all regimens were well tolerated . CHOEP should be the preferred chemotherapy regimen for young patients with good-prognosis ( normal LDH level ) aggressive lymphoma The surface Ig on each B-cell lymphoma has unique portions ( idiotypes ) , which can be recognized by the immune system . In this study , we immunized patients against the Ig expressed by their tumor and observed their clinical outcomes . After st and ard chemotherapy , 41 patients with non-Hodgkin 's B-cell lymphoma received a series of injections with a vaccine consisting of tumor Ig protein coupled to keyhole limpet hemocyanin and emulsified in an immunologic adjuvant . Subjects were observed for toxicity , immune responses , and tumor status . The median duration of follow-up of all patients is 7.3 years from diagnosis and 5.3 years from the last chemotherapy given before vaccine treatment . Twenty patients ( 49 % ) generated specific immune responses against the idiotypes of their tumor Ig . Two patients who had residual disease experienced complete tumor regression in association with the development of these immune responses . The median duration of freedom from disease progression and overall survival of all 20 patients mounting an anti-idiotype immune response are significantly prolonged compared to the patients who did not mount an immune response . Thirty-two patients were in their first remission and nine were in subsequent remissions before beginning vaccine treatments . Analysis of the 32 first remission patients also shows an improved clinical outcome for those patients who mounted a specific immune response compared to those who did not ( freedom from progression , 7.9 years v 1.3 years P = .0001 ; median survival from time of last chemotherapy not yet reached v 7 years , P = .04 ) . This study confirms an earlier report that patients with B-cell lymphoma can be induced to make a specific immune response against the Ig expressed by their own tumor . It further shows that the ability to make such an immune response is correlated with a more favorable clinical outcome . Prospect i ve controlled trials will be needed to prove a causal relationship between anti-idiotype immunity and improved clinical outcome BACKGROUND The Pediatric Oncology Group ( POG ) conducted a two-arm , r and omized study for the treatment of children and adolescents with stage III small , non-cleaved cell lymphoma ( SNCCL ) . Regimen A , based on the group 's previous best treatment for this group of patients , included cyclophosphamide ( CTX ) and high-dose methotrexate ( MTX ) , as well as vincristine ( VCR ) , prednisone ( PRED ) , and intrathecal ( IT ) chemoprophylaxis . Regimen B , based on a single institution pilot study ( Total B therapy ) , consisted of two rapidly alternating chemotherapy combinations ( CTX , VCR , doxorubicin ; MTX , and cytarabine ( Ara-C ) plus coordinated IT chemotherapy . PROCEDURE One hundred thirty-four consecutive patients were entered on this study . Seventy patients were r and omized to Regimen A , and 64 patients to Regimen B. One hundred and twenty-two patients are eligible for response . RESULTS Complete remission ( CR ) was achieved by 81 % ( 52/64 ) of patients on Regimen A , and 95 % ( 55/58 ) of patients on Regimen B ( p=0.014 one-sided ) . The two-year event-free survival ( EFS ) is 64 % ( SE=6 % ) on Regimen A , and 79 % ( SE=6 % ) on Regimen B ( p=0.027 by one-sided logrank test ) . No patient has relapsed on either regimen after a year from diagnosis , although one patient had a second malignancy at day 371 . Severe , but manageable , hematologic toxicity was seen in the majority of patients on both regimens , but was more frequent on Regimen B. CONCLUSIONS We conclude that the cure rate in stage III SNCCL is significantly improved with the use of a short , six-month chemotherapy regimen of fractionated CTX alternated with coordinated MTX and Ara-C. Results suggest that drug schedule , not simple drug selection , influences outcome Twenty-two patients with Burkitt 's lymphoma in complete remission induced by either cyclophosphamide or a combination of cyclophosphamide , oncovin and methotrexate were r and omized to receive or not to receive prophylactic cerebrospinal irradiation . Six of 11 irradiated patients relapsed with tumour of the central nervous system as compared to 4 of 11 controls . Relapse frequency appeared to be related to stage of disease on admission . It is concluded that irradiation does not prevent relapse 39 patients with marginal zone B cell lymphoma ( MZBCL ) of the parotid gl and s ( stages I or II ) were studied . They were r and omized to be treated with either radiotherapy alone ( extended fields , 4500 cGy ) or radiotherapy ( the same schedule ) plus adjuvant chemotherapy ( cyclophosphamide , vincristine and prednisone ) . The end points were survival and time to treatment failure ( TTF ) . Patients who received radiotherapy alone had a complete remission rate of 100 % , the TTF was 90 % at 5 years and overall survival at 5 years was 90 % with no statistical difference when compared with patients who received combined therapy [ 100 , 80 and 95 % , respectively ( P = 0.5 ) ] . Although adjuvant chemotherapy was well tolerated , the use of this therapeutic approach in patients with early stage MZBCL did not offer any advantage over radiotherapy alone as the initial treatment . Until now , radiotherapy was considered the treatment of choice in this clinical setting of patients Twenty-seven children with abdominal Burkitt 's lymphoma ( stage III ) , who had achieved complete remission , were entered into a prospect i ve controlled trial of adjunct treatment with Epstein-Barr virus (EBV)-specific transfer factor ( TF ) . Two patients treated with TF and 2 controls relapsed early ( less than or equal to 12 weeks ) . Two out of 12 TF-treated patients and 5 out of 11 controls subsequently suffered relapses . Time to first late relapse was longer among TF-treated patients ( p = 0.08 ) , and no late relapse occurred while a patient was receiving TF treatment . Thus it seems that specific TF might be useful in the management of endemic Burkitt 's lymphoma and also in the treatment of other virus-associated cancers and diseases We report the up date d results of an intensive treatment protocol for children ( < 18 years ) and adults ( > or = 18 years ) with advanced B-cell lymphomas . The protocol consists of two chemotherapy regimens : A , consisting of cyclophosphamide , doxorubicin , vincristine and high-dose methotrexate ( CODOX-M ) , and B , consisting of ifosfamide , etoposide , and high-dose cytarabine ( IVAC ) . Both cycles included intrathecal chemotherapy ( cytarabine or methotrexate ) . Patients received a total of four cycles in the following sequence : A , B , A , B. Sixty-six previously untreated patients , enrolled before October 1996 , were included in the present analysis . Of these , 55 had Burkitt 's or Burkitt's-like lymphoma and 11 had diffuse large B-cell lymphoma . There were 53 males ad 13 females ; 40 were children and 26 were adults ( age range , 3 to 57 years ) . To date , 61 patients have achieved a complete response to therapy . Two patients subsequently relapsed , but one of these is a long-term survivor after further therapy and a bone marrow transplant . The event-free survival rate is 85 % at I year and beyond . The median potential follow-up period is 48 months ( range , 12 to 96 months ) for patients remaining in complete remission . Neutropenia occurred in 98 % of cycles and infection in 46 % of A cycles and 50 % of B cycles , but the duration was shortened in B cycles by the administration of granulocyte colony-stimulating factor . Positive blood cultures were observed in 21 % of A cycles and 28 % of B cycles , and there have been three toxic deaths . These results are better than those achieved with an earlier version of CODOX-M , suggesting that the addition of the IVAC regimen is responsible for the improved results . The similarity of the outcome in children and adults , however , confirms our previous observation that , at least in adults younger than 60 years with Burkitt 's or Burkitt's-like lymphomas , treatment with regimens similar to those used in children is warranted Thirty patients with human immunodeficiency virus (HIV)-associated non-Hodgkin 's lymphoma ( NHL ) receiving chemotherapy with cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) were r and omized to receive either subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor ( rGM-CSF ) or no additional therapy . Recombinant rGM-CSF ( at a dose of 10 - 20 micrograms/kg/d ) was given on days 1 to 10 ( early rGM-CSF ) to the first five patients , but was changed to days 4 to 13 ( delayed rGM-CSF ) of each chemotherapy cycle in subsequent patients . Compared with the control group ( N = 10 ) , the delayed rGM-CSF group ( N = 11 ) had higher mean nadirs of the absolute neutrophil count ( 0.36 v 0.89 x 10(9)/L ; P = .009 ) , shorter mean duration s of neutropenia ( 4.9 v 1.3 days ; P = .02 ) , fewer chemotherapy cycles complicated by neutropenia and fever ( 67 % v 27 % ; P = .001 ) , fewer days hospitalized for fever and neutropenia ( 4.9 v 1.8 ; P = .004 ) , fewer reductions in chemotherapy dosages , and less frequent delays in chemotherapy administration . No significant differences were observed between patients in the control group and those in the early rGM-CSF group ( N = 5 ) . Median levels of serum HIV-1 p24 antigen decreased to 18 % and 17 % of baseline values in control ( N = 4 ) and rGM-CSF groups ( N = 6 ) , respectively , 1 week following administration of the first cycle of chemotherapy . In the third week after chemotherapy , median antigen levels remained below baseline in the control group , but rose to 243 % of baseline values in the rGM-CSF group ( P = .01 ) , suggesting stimulation of HIV replication . The effect of this change in HIV activity on clinical outcome of treated patients could not be determined , and therefore the clinical significance of this finding remains unclear . Complete response rates of 67 % , 70 % , and 60 % were observed in the control , delayed rGM-CSF , and early rGM-CSF groups , respectively , with corresponding survival times of 9.0 , 11.4 , and 8.0 months The B-cell antigen CD20 is expressed on normal B cells and by nearly all B-cell lymphomas . This nonmodulating antigen provides an excellent target for antibody-directed therapies . A chimeric anti-CD20 antibody ( IDEC-C2B8 ) , consisting of human IgG1-kappa constant regions and variable regions from the murine monoclonal anti-CD20 antibody IDEC-2B8 , has been produced for clinical trials . It lyses CD20 + cells in vitro via complement and antibody-dependent cell-mediated lysis . Pre clinical studies have shown that the chimeric antibody selectively depletes B cells in blood and lymph nodes in macaque monkeys . In this phase I clinical trial , 15 patients ( 3 per dose level ) with relapsed low- grade B-cell lymphoma were treated with a single dose ( 10 , 50 , 100 , 250 , or 500 mg/m2 ) of antibody administered intravenously . Treatment-related symptoms correlated with the number of circulating CD20 cells and grade II events consisted of fever ( 5 patients ) ; nausea ( 2 ) , rigor ( 2 ) , orthostatic hypotension ( 2 ) , bronchospasm ( 1 ) , and thrombocytopenia ( 1 ) . No significant toxicities were observed during the 3 months of follow-up . Serum C3 , IgG , and IgM levels , neutrophils , and T cells were largely unchanged . At the three higher dose levels , pharmacokinetics of the free antibody showed a serum half-life of 4.4 days ( range , 1.6 to 10.5 ) . Levels greater than 10 micrograms/mL persisted in 6 of 9 patients for more than 14 days . No quantifiable immune responses to the infused antibody have been detected . CD20 + B cells were rapidly and specifically depleted in the peripheral blood at 24 to 72 hours and remained depleted for at least 2 to 3 months in most patients . Two-week postinfusion tumor biopsies showed the chimeric antibody bound to tumor cells and a decrease in the percentage of B cells . Tumor regressions occurred in 6 of 15 patients ( 2 partial and 4 minor responses ) . The results of this single-dose trial have been used to design a multiple-dose phase I/II study PURPOSE Radioimmunotherapy combines biologic and radiolytic mechanisms to target and destroy tumor cells , thus offering a needed therapeutic alternative for refractory non-Hodgkin 's lymphoma ( NHL ) patients . This phase III r and omized study compares the novel radioimmunotherapy yttrium-90 ( (90)Y ) ibritumomab tiuxetan with a control immunotherapy , rituximab , in 143 patients with relapsed or refractory low- grade , follicular , or transformed CD20(+ ) transformed NHL . PATIENTS AND METHODS Patients received either a single intravenous ( IV ) dose of (90)Y ibritumomab tiuxetan 0.4 mCi/kg ( n = 73 ) or rituximab 375 mg/m(2 ) IV weekly for four doses ( n = 70 ) . The radioimmunotherapy group was pretreated with two rituximab doses ( 250 mg/m(2 ) ) to improve biodistribution and one dose of indium-111 ibritumomab tiuxetan for imaging and dosimetry . The primary end point , overall response rate ( ORR ) , was assessed by an independent , blinded , lymphoma expert panel . RESULTS ORR was 80 % for the (90)Y ibritumomab tiuxetan group versus 56 % for the rituximab group ( P = .002 ) . Complete response ( CR ) rates were 30 % and 16 % in the (90)Y ibritumomab tiuxetan and rituximab groups , respectively ( P = .04 ) . An additional 4 % achieved an unconfirmed CR in each group . Kaplan-Meier estimated median duration of response was 14.2 months in the (90)Y ibritumomab tiuxetan group versus 12.1 months in the control group ( P = .6 ) , and time to progression was 11.2 versus 10.1 months ( P = .173 ) in all patients . Durable responses of > or = 6 months were 64 % versus 47 % ( P = .030 ) . Reversible myelosuppression was the primary toxicity noted with (90)Y ibritumomab tiuxetan . CONCLUSION Radioimmunotherapy with (90)Y ibritumomab tiuxetan is well tolerated and produces statistically and clinical ly significant higher ORR and CR compared with rituximab alone From April 1984 to December 1987 , the French Pediatric Oncology Society ( SFOP ) organized a r and omized trial for advanced-stage B-cell lymphoma without CNS involvement to study the possibility of reducing the length of treatment to 4 months . After receiving the same three intensive six-drug induction courses based on high-dose fractionated cyclophosphamide , high-dose methotrexate ( HD MTX ) , and cytarabine in continuous infusion , patients were evaluated for remission . Those who achieved complete remission ( CR ) were r and omized between a long arm ( five additional courses with two additional drugs ; 16 weeks of treatment ) and a short arm ( two additional courses ; 5 weeks ) . For patients in partial remission ( PR ) , intensification of treatment was indicated . Two hundred sixteen patients were registered : 15 stage II nasopharyngeal and extensive facial tumors , 167 stage III , and 34 stage IV , 20 of the latter having more than 25 % blast cells in bone marrow . The primary sites of involvement were abdomen in 172 , head and neck in 30 , thorax in two , and other sites in 12 . One hundred sixty-seven patients are alive in first CR with a minimum follow-up of 18 months ; four are lost to follow-up . Eight patients died from initial treatment failure , 14 died from toxicity or deaths unrelated to tumor or treatment , and 27 relapsed . The event-free survival ( EFS ) , with a median follow-up of 38 months , is 78 % ( SE 3 ) for all the patients , 73 % ( SE 11 ) for the stage II patients , 80 % ( SE 3 ) for the stage III patients , and 68 % ( SE 8) for the stage IV and acute lymphoblastic leukemia ( ALL ) patients . One hundred sixty-six patients were r and omized : 82 in the short arm and 84 in the long arm . EFS is , respectively , 89 % and 87 % . Statistical analysis confirms equivalence of both treatment arms with regard to EFS . Moreover , morbidity was lower in the short arm . This study confirms the high survival rate obtained in the previous LMB 0281 study without radiotherapy or debulking surgery and demonstrates the effectiveness of short treatment The aims of trial NHL-BFM 90 for patients ( pts ) suffering from B-cell neoplasms are to prove whether : 1 . Treatment for pts with complete resection can be reduced from 3 to 2 therapy courses ; 2 . Results for pts of stage III with large abdominal tumors can be improved by high dose ( HD ) chemotherapy ; 3 . Survival for pts with incomplete initial response can be improved by therapy intensification ; 4 . Intraventricularly applied CNS chemotherapy can improve the outcome for CNS positive pts . Therapy is stratified into 3 branches . Branch 1 : completely resected ; branch 2 : not resected , extra-abdominal localization only or abdominal localization and LDH < 500 U/l ; branch 3 : abdominal localization and LDH > or = 500 U/l , and all pts with BM or/ and CNS involvement or multifocal bone disease . A 5-day prephase is followed by 2 ( R1 ) , 4 ( R2 ) , 6 ( R3 ) therapy courses composed of dexamethasone ( DEXA ) , methotrexate ( MTX ) 5 g/m2/24 h ( in branch R1 , 500 mg/m2 ) , MTX/Cytarabine (ARA-C)/prednisolone ( PRED ) i.th . , vincristine ( not in branch R1 ) , ifosfamide alternating with cyclophosphamide , ARA-C/etoposide ( VP16 ) alternating with doxorubicin . CNS pos . pts receive MTX/ARA-C/PRED applied intraventricularly . Pts with incomplete response after 2 courses receive an intensification ( DEXA , Vindesine , HD-ARA-C , VP16 , and MTX/ARA-C/PRED i.th . ) . Pts with viable tumor after the intensified course receive mega-dose chemotherapy with autologous BM rescue ( aBMT ) . From 4/1990 to 12/1992 , 228 pts were registered ; 212 pts are evaluable for response . The probability of event free survival ( pEFS ) at 3 years is 89 + /- 2 % for the whole group , 97 + /- 3 % for pts of branch R1 ( n = 32 ) , 99 + /- 1 % for patients of branch R2 ( n = 87 ) , and 77 + /- 4 % for patients of branch R3 ( n = 94 ) ( median observation time 21 months ) . 7 pts of branch R3 died early due to infections . 15 pts failed therapy ( one pt each in branch R1 , and R2 , 13 pts in branch R3 ) . pEFS for pts with stage III abdominal disease and LDH > or = 500 U/l is 80 + /- 6 as compared to 53 + /- 8 % in the preceding studies ( p < .02 ) . Of 13 evaluable pts with CNS disease 3 died early of infection , however none suffered from relapse . Only 1 of 22 pts of branch R2 who had residual tumors after 2 therapy courses suffered from progress in contrast to 9 of 33 such pts of branch R3 . Only 2 pts had viable tumor after the intensification course CC . They received aBMT , both are in CCR . ( ABSTRACT TRUNCATED AT 400 WORDS PURPOSE To compare the benefit of maintenance rituximab therapy versus rituximab re-treatment at progression in patients with previously treated indolent non-Hodgkin 's lymphoma . PATIENTS AND METHODS Between June 1998 and August 2002 , 114 patients who had received previous chemotherapy for indolent non-Hodgkin 's lymphoma were treated with a st and ard 4-week course of rituximab . Patients with objective response or stable disease were r and omly assigned to receive either maintenance rituximab therapy ( st and ard 4-week courses administered at 6-month intervals ) or rituximab re-treatment at the time of lymphoma progression . The duration of rituximab benefit was measured from the date of first rituximab treatment until the date other treatment was required . RESULTS Ninety ( 79 % ) of 114 patients had objective response or stable disease after initial rituximab treatment , and were r and omly assigned to treatment . Progression-free survival was prolonged in the maintenance group ( 31.3 v 7.4 months ; P = .007 ) . Final overall and complete response rates were higher in the maintenance group . Duration of rituximab benefit was similar in the maintenance and re-treatment groups ( 31.3 v 27.4 months , respectively ) . More maintenance patients remain in continuous remission , and more are currently in complete remission . Both treatment approaches were well tolerated . CONCLUSION In patients who have objective response or stable disease with single-agent rituximab therapy , duration of rituximab benefit is substantially prolonged with either scheduled maintenance treatment or rituximab re-treatment at the time of progression . At present , the magnitude of benefit with either approach appears similar . However , additional follow-up of this trial is required , and completion of phase III r and omized trials is necessary to definitively answer this question Members of the Childrens Cancer Study Group treated 234 eligible patients in a r and omized trial design ed to study the relative effectiveness of two therapy programs for the treatment of childhood and adolescent non-Hodgkin 's lymphoma . Two chemotherapeutic strategies were compared : a 4-drug regimen ( COMP ) and a 10-drug regimen ( modified LSA2-L2 ) . Failure-free survival for all patients was 60 per cent at 24 months . In patients with disseminated disease treatment success was influenced by both the histologic subtype of disease and the therapeutic regimen followed . The 10-drug program was more effective than the 4-drug program in patients with disseminated lymphoblastic disease ( two-year failure-free survival rate , 76 vs. 26 per cent , respectively ; P = 0.0002 ) , whereas the 4-drug program was more effective than the 10-drug program in those with nonlymphoblastic disease ( 57 vs. 28 per cent , respectively , P = 0.008 ) . The less toxic , more easily administered 4-drug regimen was as effective as the 10-drug regimen in patients with localized disease ( 89 vs. 84 per cent , respectively ) Summary . Historically , the survival of children and adolescents with Burkitt 's and Burkitt‐like lymphoma had been poor . Recently , short and intensive chemotherapy appears to have improved disease outcome . We therefore review ed the results of four successive Children 's Cancer Group trials conducted on 470 children with disseminated Burkitt 's and Burkitt‐like lymphoma . Of the patients studied , the median age was 8 years ( 0–21 years ) , the male : female ratio was 4:1 , 58 % had lactate dehydrogenase ( LDH ) ≥ 500 IU/l , 23 % had M2 or M3 bone marrow ( BM ) , and 12 % demonstrated central nervous system involvement . In a multivariate analysis , the 4‐year event‐free survival ( EFS ) in patients ≥ 15‐years‐old compared with < 15‐year‐old was 34 ± 7 versus 59 ± 2 % ( P < 0·05 ) , the 4‐year EFS of M2/M3 compared with M1 BM was 38 ± 5 versus 63 ± 3 % ( P < 0·001 ) , and the 4‐year EFS with LDH ≥ 500 IU/l compared with LDH < 500 IU/l was 49 ± 3 versus 71 ± 4 % ( P < 0·001 ) . Furthermore , patients treated on the most recent protocol , which was short and more intensive , had a significantly improved survival compared with those on previous trials ( 4‐year EFS 80 ± 6 versus 54 ± 2 % , P < 0·001 ) . In summary , the outcome for childhood Burkitt 's and Burkitt‐like lymphoma has recently improved with the use of short and intensive B‐cell non‐Hodgkin 's lymphoma‐directed therapy Meningeal involvement with Burkitt lymphoma cells constitutes the most challenging therapeutic problem in the management of Burkitt 's tumour . The results of intrathecal chemotherapy with methotrexate or cytosine arabinoside in 55 episodes of malignant pleocytosis in 38 patients with Burkitt 's tumour are described . The response was complete in nearly all patients after the administration of either agent . Cerebrospinal fluid ( C.S.F. ) remissions were more prolonged in patients receiving intrathecal methotrexate or cytosine arabinoside daily for four days as opposed to a 10-day schedule . A controlled r and omized trial of “ prophylactic ” intrathecal chemotherapy in patients without malignant cells in the C.S.F. on admission showed no protective effect against the subsequent development of malignant pleocytosis . Future therapeutic approaches are considered in the light of these results Results of treatment of 117 patients with Burkitt 's lymphoma followed for a minimum of 18 months were analyzed . All patients were clinical ly staged and treated according to r and omized clinical trials . Sixteen patients ( 14 % ) died within the first week of treatment of causes related to widespread tumor . Ninety‐five of the remaining 101 evaluable patients achieved complete remission ( 95 % ) , while six had partial responses and eventually died . The frequency of relapse was significantly lower in patients with localized tumors ( 39 % ) as compared to patients with generalized disease ( 70 % ) , but was unaffected by the intensity of the initial therapeutic regimen . Patients who developed early relapse ( within 10 weeks of first treatment ) had a less favorable prognosis than patients who relapsed beyond this period . Preliminary results of a current immunotherapeutic trial using BCG following cyclophosphamide‐induced remission suggest a protective effect of this treatment on the development of extradural relapse . These results provide guidelines for future therapeutic approaches which are discussed The results of a clinical trial in patients with generalized Burkitt 's lymphoma using either multiple doses of cyclophosphamide or a cyclic , sequential regimen employing cylophosphamide , vincristine , methotrexate , and cytosine arabinoside ( TRIKE ) are reported . Of 42 evaluable patients 24 received cyclophosphamide and 18 received TRIKE . No significant differences were encountered between either group with respect to remission induction , relapse rate or survival . Remission duration was significantly prolonged in the patients receiving cyclophosphamide , but this event has little effect on survival . Although intensive chemotherapy is probably necessary in patients with generalized Burkitt 's lymphoma , other variables such as meningeal involvement and immunologic factors appear to affect relapse and survival . Chimiotherapie intensive chez les malades atteints de lymphome de Burkitt generalise Les auteurs communiquent les result ats d'un essai clinique effectue sur des malades atteints de lymphome de Burkitt generalise , pour lequel ils ont utilise des doses multiples de cyclophosphamide ou un traitement sequentiel et cyclique comprenant du cyclophosphamide , de la vincristine , du methotrexate et de la cytosine arabinoside ( TRIKE ) . Sur 42 malades se prětant a l'evaluation , 24 ont recu du cyclophosphamide et 18 le traitement TRIKE . Aucune difference significative n'a ete observee entre les groupes pour ce qui est de l'induction de la remission , du pourcentage de rechutes ou de la survie . La duree de la remission a ete notablement prolongee chez les malades qui ont recu du cyclophosphamide , mais cela n'a eu que peu d'influence sur la survie . Bien qu'une chimiotherapie intensive soit probablement necessaire chez les sujets atteints de lymphome de Burkitt generalise , d'autres variables telles que l'envahissement des meninges et certains facteurs immunologiques semblent influer sur les rechutes et la survie Rituximab ( Rituxan ; Genentech , Inc , South San Francisco , CA and IDEC Pharmaceutical Corporation , San Diego , CA ) is a monoclonal antibody that targets the CD20 antigen present in most B-cell non-Hodgkin 's lymphomas . Previous studies have shown overall response rates ( ORR ) of approximately 50 % in relapsed patients . Ibritumomab is the murine parent anti-CD20 antibody that is linked through a MX-DTPA chelator to yttrium 90 ( 90Y ) to form the radioimmunoconjugate 90Y-ibritumomab tiuxetan ( Zevalin ; IDEC Pharmaceuticals , San Diego , CA ) . A phase I study of 90Y-ibritumomab tiuxetan determined that 0.4 mCi/kg was the maximum tolerated dose , and responses were reported in 67 % of all patients and in 82 % of patients with low- grade non-Hodgkin 's lymphoma . A separate trial r and omized eligible patients to either rituximab or 90Y-ibritumomab tiuxetan . An interim analysis of the first 90 patients showed an ORR of 80 % with 90Y-ibritumomab tiuxetan versus 44 % with rituximab ( P < .05 ) . A subsequent trial for patients with rituximab-refractory disease showed a 46 % ORR . These studies show that 90Y-ibritumomab tiuxetan is an active agent in relapsed non-Hodgkin 's lymphoma and appears to have a higher ORR compared with unconjugated rituximab A controlled r and omised trial was carried out to evaluate the efficacy of BCG immunotherapy in preventing relapse in patients with Burkitt 's lymphoma in whom remission had been induced with cyclophosphamide . Twenty-one patients were treated with BCG , and 19 were controls . Eleven patients in each group relapsed during a follow-up period long enough to make it unlikely that further relapses would occur . There were no significant differences in the length of remission or the site of relapse that could be attributed to treatment . Eleven patients died : of these none of the six patients in the BCG group but all of the five in the control group had stage D lymphomas . BCG treatment increased the rate of recovery from tumour-induced immunosuppression , but within the BCG group immunocompetence improved most rapidly in the patients who relapsed-a finding that appears to contradict the tenet retionalising the use of immunological adjuvants as treatment The Pediatric Oncology Group ( POG ) investigated a high-dose cyclophosphamide ( CPM ) high-dose methotrexate ( MTX ) regimen to determine therapeutic efficacy in confirmed advanced nonlymphoblastic non-Hodgkin 's lymphoma ( NHL ) ( stages III and IV ) and B-cell acute lymphatic leukemia ( B-ALL ) in children . Another goal was to determine the comparative effectiveness of shortened maintenance treatment ( 2 versus 6 courses ) in the study population . Systemic induction therapy included vincristine , prednisone , cyclophosphamide , and intermediate-dose MTX with leucovorin rescue . Superimposed intrathecal ( IT ) therapy included cytosine arabinoside for 2 successive days followed on day 3 by MTX . Intrathecal MTX was given 3 times during induction . At the end of induction , 2 days of triple ( hydrocortisone , MTX , and cytosine arabinoside ) therapy were given intrathecally ( TIT ) . All patients then received a consolidation course of 4 doses of TIT , 2 doses of cyclophosphamide , and 4 more courses of vincristine and MTX with leucovorin rescue . Patients were then r and omized to receive either 2 or 6 cycles of vincristine plus MTX with leucovorin rescue . The TIT was given with each cycle . Complete response rates by histology and Murphy stage ( 1 ) were as follows : undifferentiated lymphoma ( DUL ) stage III , 84/105 ( 80 % ) : stage IV , 5/12 ( 42 % ) ; and other NHL [ primarily large cell lymphoma ( LCL ) ] stage III , 21/28 ( 75 % ) ; stage IV , 2/3 ( 67 % ) . Event-free survival ( EFS ) at greater than 2 years was similar for patients with DUL and LCL , i.e. , 65 and 61 % , respectively . No significant difference in outcome was noted between patient groups receiving 2 or 6 maintenance treatments ( p = .76 ) . Treatment was notable for its modest toxicity following the early change to single-dose CPM therapy . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Burkitt's/Burkitt-like lymphoma ( BL/BLL ) are highly aggressive lymphomas mainly affecting children and young adults . We report the results in adolescent and adult patients with the use of three successive regimens . PATIENTS AND METHODS Forty-nine patients aged 15 - 70 years admitted to the Norwegian Radium Hospital in the period 1982 - 2001 with a diagnosis of BL/BLL on histological review and who were given chemotherapy with curative intent are included in this analysis . Up to 1987 patients were given doxorubicin-based chemotherapy supplemented with intravenous and intrathecal methotrexate ( MmCHOP ) . From 1987 to 1994 , patients who obtained complete remission upon this regimen were consoli date d with high-dose therapy with stem-cell support ( MmCHOP + HDT ) . In 1995 we introduced as frontline therapy the German Berlin-Frankfurt-Munster ( BFM ) regimen . RESULTS By intention to treat analyses , the progression-free survival rates for patients who received MmCHOP ( n=13 ) , MmCHOP + HDT ( n=17 ) or BFM therapy ( n=19 ) are 30.8 % , 70.6 % and 73.7 % , respectively . In the groups of patients who received either the BFM regimen or MmCHOP + HDT , all patients who obtained complete remission upon induction therapy are continuously disease free . There was no treatment-related death . CONCLUSIONS BL/BLL in adolescents and adults can successfully be treated with 5-day blocks of intensified chemotherapy such as the BFM regimen or CHOP/methotrexate-based chemotherapy consoli date d with high-dose therapy . Using the BFM regimen , continuous remissions are obtained without additional myeloablative chemotherapy OBJECTIVE --To ascertain if low-dose multiagent chemotherapy , with central nervous system prophylaxis and antiretroviral therapy , might be associated with increased efficacy and decreased risk of intercurrent infection in patients with malignant lymphoma related to the acquired immunodeficiency syndrome ( AIDS ) . DESIGN --A phase II prospect i ve clinical trial , with median follow-up of 33 months . SETTING --Eight university hospitals , within the context of the AIDS Clinical Trials Units , sponsored by the National Institute of Allergy and Infectious Diseases . PATIENTS --Forty-two patients with AIDS-related malignant lymphoma . All were evaluable for toxicity assessment , and 35 for response . INTERVENTION --A low-dose modification of the M-BACOD regimen ( day 1 ) : cyclophosphamide , 300 mg/m2 intravenously ( IV ) ; doxorubicin , 25 mg/m2 IV ; vincristine sulfate , 1.4 mg/m2 IV ; bleomycin , 4 mg/m2 IV ; dexamethasone , 3 mg/m2 orally on days 1 through 5 ; methotrexate , 500 mg/m2 IV on day 15 , with leucovorin rescue . Intrathecal cytosine arabinoside ( 50 mg ) to all on days 1 , 8 , 21 , and 28 , with radiation therapy to a helmet field to those with central nervous system involvement . Zidovudine for 12 months after completion of four to six cycles of chemotherapy . MAIN OUTCOME MEASURES --Response rate and number of opportunistic infections . RESULTS --Response rate was 51 % with a complete response of 46 % . Of 16 complete responses , relapse occurred in four , none isolated to the central nervous system . Opportunistic infections occurred in 21 % of those receiving treatment . Median duration of survival among all 42 patients is 5.6 months , 6.5 months in 35 patients evaluable for response , and 15 months in patients with complete response . Lower concentration of CD4 cells , history of prior AIDS , bone marrow involvement , and stage IV disease were independently associated with decreased survival . CONCLUSIONS --Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance may be associated with durable remissions in AIDS-related lymphoma with fewer opportunistic infections than noted in prior reports The goals of study NHL-BFM 90 for the therapy group Non-B NHL are to prospect ively evaluate the dynamic of tumor regression and the persistence of a residual mass after induction therapy for its prognostic impact . Patients ( pts ) of stages I and II receive induction composed of prednisone , vincristine ( VCR ) , daunorubicin , L-asparaginase ( L-ASP ) , cyclophosphamide ( CP ) , cytarabine ( ARA-C ) , 6-mercaptopurine ( 6-MP ) and intrathecally ( i.th . ) methotrexate ( MTX ) , followed by consolidation ( 6-MP , MTX 5 g/m2 x 4 , MTX i.th . ) , and maintenance up to 24 months . Pts of stages III and IV receive additionally reinduction ( Dexamethasone , VCR , doxorubicin , L-ASP , CP , ARA-C , 6-thioguanine , MTX i.th . ) and cranial irradiation . Pts with < 70 % tumor regression at day 33 of induction receive an intensified chemotherapy . Pts with > 70 % tumor regression at day 33 but a persistent mass at the end of induction have a surgical resection . Pts with a completely necrotic residual mass continue with consolidation therapy . Pts with active residual lymphoma receive an intensified chemotherapy . No local radiotherapy is given . From 4/1990 to 12/1992 , 80 pts were registered ; 71 pts are evaluable for response . The distribution of stages is as follows : 6 , 1 , 47 , 17 pts of stage I , II , III , IV , respectively . The probability of event free survival at 3 years is 87 + /- 4 % for the whole group ( median observation time 21 months ) . 66 pts are evaluable for the dynamic of response . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE To evaluate the safety , pharmacokinetics , and biologic effect of multiple doses of the chimeric anti-CD20 monoclonal antibody ( mAb ) IDEC-C2B8 in patients with relapsed B-cell lymphoma . PATIENTS AND METHODS Twenty patients with relapsed low- grade ( n = 15 ) or intermediate-/high- grade ( n = 5 ) lymphoma received weekly infusions times four of 125 mg/m2 ( n = 3 ) , 250 mg/m2 ( n = 7 ) , or 375 mg/m2 ( n = 10 ) of IDEC-C2B8 . RESULTS Infusional side effects during the initial infusion were mainly grade I/II fever , asthenia , chills , nausea , rash , and urticaria . More serious events were rare . Peripheral-blood B cells were rapidly depleted and slowly recovered over 3 to 6 months . There was no change in mean immunoglobulin ( Ig ) levels . Antibody serum half-life ( and maximum concentration [ Cmax ] ) generally increased between the first and fourth infusions ( 33.2 hours v 76.6 hours , respectively ) following the 375-mg/m2 doses . Six of 18 assessable patients had a partial remission ( PR ) , with a median time to disease progression of 6.4 months ( range , 3 to 21.7 ) . Minor responses ( MRs ) were observed in five patients and progressive disease ( PD ) in seven . Tumor responses occurred in peripheral blood , bone marrow ( BM ) , spleen , bulky lymph nodes , and extranodal sites , and in patients who had relapsed following high-dose myeloablative chemotherapy . Six of 14 patients ( 40 % ) with a low- grade histology responded . Four of six with bulky disease had a PR . CONCLUSION IDEC-C2B8 chimeric anti-CD20 mAb therapy is well tolerated and has clinical activity in patients with relapsed B-cell lymphoma . The 375-mg/m2 dose has been selected for a phase II trial in patients with relapsed low- grade or follicular B-cell lymphoma PURPOSE To examine the impact of initial CNS involvement on outcome and patterns of failure in patients with disseminated small noncleaved-cell lymphoma and B-cell leukemia who were treated in four successive Children 's Cancer Group trials . PATIENTS AND METHODS Of 462 patients with disseminated disease , 49 ( 10.6 % ) had CNS disease at diagnosis ( CNS+ ) . CNS disease included meningeal disease or CNS parenchymal masses with or without cranial neuropathies ( CSF+/Mass ; CNPs ) in 36 patients and isolated CNPs in 13 . Of the CNS+ patients , 28 had M2 ( 5 % to 25 % blasts ) or M3 ( > 25 % blasts ) bone marrow involvement . All patients received protocol -based systemic and intrathecal chemotherapy . Thirty-six patients also received CNS irradiation . RESULTS Relapses occurred in 21 ( 43 % ) of 49 patients , predominantly in the CNS ( 71 % ) and bone marrow ( 52 % ) . The 3-year event-free survival + /- SE for all patients with CNS+ disease was 45 % + /- 7 % . Patients with CSF+/Mass had a nominally higher treatment failure rate compared with patients with CNS- after adjusting for marrow status and lactate dehydrogenase ( LDH ) diagnosis , with a relative failure rate ( RFR ) of 1.52 ( 95 % confidence interval [ CI ] , 0.88 to 2.6 ; P = .15 ) . In comparison , the RFRs for patients with M2 or M3 marrow and for those with LDH levels greater than 500 IU/L after adjusting for CNS disease were 1.4 ( 95 % CI , 0.96 to 2.0 ; P = .029 ) and 2.2 ( 95 % CI , 1.5 to 3.0 ; P < .001 ) , respectively . The RFR for patients with isolated CNPs was 0.87 ( 95 % CI , 0.36 to 2.1 ; P = .76 ) . CONCLUSION We conclude that , with the treatments used during the period covered by these studies , the presence of CSF+/Mass CNS disease at diagnosis was associated with a nominally worse outcome independent of initial bone marrow status and LDH level , but the effect was not statistically significant PURPOSE To compare a short intensified regimen followed by sequential consolidation therapy ( doxorubicin , cyclophosphamide , vindesine , bleomycin , and prednisone [ ACVBP ] ) to the st and ard regimen of methotrexate , bleomycin , cyclophosphamide , and etoposide ( m-BACOD ) in patients with low-risk aggressive lymphoma . PATIENTS AND METHODS A total of 752 patients with intermediate- or high- grade lymphoma and no adverse prognostic factors ( Eastern Cooperative Oncology Group performance status of 2 to 4 , > /= two extranodal sites of disease , tumor burden > /= 10 cm in largest dimension , bone marrow or CNS involvement , Burkitt 's or lymphoblastic subtypes ) were registered . Of 673 eligible patients , 332 received ACVBP and 341 received m-BACOD . RESULTS The complete remission rate was identical ( 86 % ) in the two groups . With a median follow-up duration of 7 years , the 5-year failure-free survival ( FFS ) rate was 65 % in the ACVBP group and 61 % in the m-BACOD group ( P = .16 ) . The 5-year overall survival rate was 75 % in the ACVBP group and 73 % in the m-BACOD group ( P = .47 ) . ACVBP was responsible for more severe and life-threatening infections ( P < .01 ) , but m-BACOD caused more pulmonary toxicity ( P < .001 ) . The number of treatment-related deaths did not differ between the two regimens . A multivariate analysis indicated that ACVBP was associated with a longer FFS in patients with two or three risk factors of the International Prognostic Index . CONCLUSION In this population of patients with low-risk aggressive lymphoma , toxicities of the regimens are different , but the rates of response and survival are identical . The survival advantage of ACVBP over st and ard regimen in patients with advanced disease is suggested by this analysis but remains to be assessed in prospect i ve studies specifically design ed for this purpose |
13,514 | 26,252,417 | There is consistent evidence to support potentially modifiable correlates/determinants of SSB consumption in young children acting at parental ( modelling ) , child ( TV viewing ) and environmental ( school policy ) levels | Sugar-sweetened beverage ( SSB ) consumption is associated with adverse health outcomes .
Improved underst and ing of the determinants will inform effective interventions to reduce SSB consumption . | Background Obesity has become a global public health problem , which also affects children . It has been proposed that the educational interventions during childhood could be a key strategy in the prevention of obesity . Objective To evaluate the efficacy of an intervention on food habits and physical activity in school children . Methods A 2-year cluster-r and omised prospect i ve study with two parallel arms was used to evaluate an intervention programme in children in their first year of primary schooling ( 5–6 years of age ) in schools in the city of Granollers . The intervention consisted of the promotion of healthy eating habits and physical activity by means of the educational methodology Investigation , Vision , Action and Change ( IVAC ) . At the beginning and at the end of the study ( 2006 and 2008 ) the weight and height of each child was measured in situ , while the families were given a self-report physical activity question naire and the Krece Plus quick test . Results Two years after the beginning of the study , the body mass index of the children in the control group was 0.89 kg/m2 higher than that of the intervention schools . The intervention reduced by 62 % the prevalence of overweight children . Similarly , the proportion of children that ate a second piece of fruit and took part in an after-school physical activity increased in the intervention group . In the control group , the weekly consumption of fish was reduced . Conclusions The educational intervention in healthy eating habits and physical activity in the school could contribute to lessen the current increase in child obesity The current review aim ed to systematic ally identify dietary , physical activity and sedentary behaviours in preschool children ( 4 - 6 years of age ) that are prospect ively related to overweight or obesity later in childhood . Prospect i ve studies published between January 1990 and June 2010 were selected from search es in PubMed , EMBASE , PsycINFO , CINAHL and Cochrane Library . Studies examining the prospect i ve association between at least one relevant behaviour measured during preschool period ( children aged 4 - 6 years at baseline ) in relation to at least one anthropometric measurement at follow-up ( age < 18 years ) were included . Harvest plots were used to summarize the results and draw conclusions from the evidence . Of the 8,718 retrieved papers , 23 papers reporting on 15 different study sample s were included in this review . Strong evidence was found for an inverse association between total physical activity and overweight . Moderate evidence was observed for a positive association between television viewing and overweight . Because of the heterogeneity in the assessed dietary behaviours , insufficient evidence was found for an association between dietary intake or specific dietary behaviours and overweight . These results suggest that interventions aim ing to prevent overweight among preschool children should focus on promotion of total physical activity and limitation of screen time and that further research is needed to establish whether and which dietary behaviours are important for obesity prevention in this age group . However , despite the lack of evidence for dietary behaviours from the present review , future interventions may already target specific dietary behaviours that are highly prevalent and for which there a clear rationale as well as preliminary evidence that these behaviours are associated with overweight OBJECTIVE The purpose of the present study was to evaluate the effects of a school-based , 2-year , multi-component intervention on BMI , eating and physical activity behaviour in Fl and ers , Belgium , targeting children aged 3 - 6 years in communities of high and low socio-economic status ( SES ) . DESIGN Cluster-r and omized controlled trial . SETTING Thirty-one pre- primary and primary schools in three different intervention communities and three paired-matched ( on SES profile ) control communities in Fl and ers , Belgium . SUBJECTS BMI Z-scores at baseline and follow-up were calculated for 1102 children . Question naires with sociodemographic data and FFQ were available from 694 of these 1102 children . RESULTS No significant effects were found on BMI Z-scores for the total sample . However , there was a significant decrease in BMI Z-score of 0·11 in the low-SES intervention community compared with the low-SES control community , where the BMI Z-score increased by 0·04 ( F = 6·26 , P = 0·01 ) . No significant intervention effects could be found for eating behaviour , physical activity or screen-time . There were no significant interaction effects of age and gender of the children on the outcome variables . CONCLUSIONS Although no significant effects were found for BMI Z-scores in the total sample , this intervention had a promising effect in the low-SES community of reducing excess weight gain among young children Background The aim of these review s is to inform the design and content of interventions to reduce obesity in young children . The behaviors that are associated with obesity/overweight have been studied extensively ; however , the factors associated with these behaviors in young children ( 0 to 6 years ) have not been systematic ally review ed . Over the past few years the focus of obesity prevention has shifted to preschool children because of the high prevalence of obesity at school entry and recognition that habits formed in early life could track into adulthood . In order to develop effective interventions and change behavior , it is important to underst and the factors that are associated with those behaviors . For example , we need to underst and whether it would be more important to target the family , childcare setting s or the wider environment and identify the most effective way of changing these energy balance related behaviors . Methods / Design Quantitative ( intervention and observational ) and qualitative literature on determinants/correlates of fruit and vegetable intake , sugar sweetened beverage and other unhealthy diet intake , and physical activity and sedentary behaviors in young children will be systematic ally identified , mapped and review ed . A common search strategy ( no language or period restrictions ) will be used to identify papers from eight electronic data bases and this will be supplemented by h and - search ing . Next , studies in developed countries that examine the factors associated with these behaviors in children aged 0 to 6 years ( at baseline ) will be screened and mapped descriptively followed by in-depth data extraction , quality assessment and synthesis . Data from quantitative studies will be summarized using either forest plots or harvest plots and narrative synthesis , and qualitative studies using thematic analysis . Qualitative evidence will be integrated with the quantitative evidence , using a parallel synthesis approach , to provide a deeper underst and ing of effective strategies to influence these energy balance related behaviors . Discussion In addition to updating and mapping current research , these review s will be the first to comprehensively synthesize and integrate both the quantitative and qualitative evidence pertaining to determinants/correlates/barriers/facilitators of obesity related behaviors in this young age group ( 0 to 6 years ) with the aim of informing future interventions . Systematic review registration International Prospect i ve Register for Systematic Review s ( PROSPERO ) Registration number : BACKGROUND Increased intake of sugar-sweetened beverages and fruit juice has been associated with overweight in children . OBJECTIVE This study prospect ively assessed beverage consumption patterns and their relationship with weight status in a cohort of children born at different risk for obesity . METHODS AND PROCEDURES Participants were children born at low risk ( n = 27 ) or high risk ( n = 22 ) for obesity based on maternal prepregnancy BMI ( kg/m(2 ) ) . Daily beverage consumption was generated from 3-day food records from children aged 3 - 6 years and coded into seven beverage categories ( milk , fruit juice , fruit drinks , caloric and non-caloric soda , soft drinks including and excluding fruit juice ) . Child anthropometric measures were assessed yearly . RESULTS High-risk children consumed a greater percentage of daily calories from beverages at age 3 , more fruit juice at ages 3 and 4 , more soft drinks ( including fruit juice ) at ages 3 - 5 , and more soda at age 6 compared to low-risk children . Longitudinal analyses showed that a greater 3-year increase in soda intake was associated with an increased change in waist circumference , whereas a greater increase in milk intake was associated with a reduced change in waist circumference . There was no significant association between change in intake from any of the beverage categories and change in BMI z-score across analyses . DISCUSSION Children 's familial predisposition to obesity may differentially affect their beverage consumption patterns . Future research should examine the extent to which dietary factors may play a role in pediatric body fat deposition over time Objective : To examine the types of drinks consumed by children at 18 months of age , determine any associations with socio-demographic characteristics and investigate the use of a bottle for providing these drinks . Design : A total of 1026 r and omly chosen children from the Avon Longitudinal Study of Pregnancy and Childhood ( ALSPAC ) were studied . Methods : As part of a dietary diary completed when their children were 18 months of age , mothers were asked to record all drinks consumed over a 24 h period and to report the containers used to give these drinks . Socio-demographic characteristics were obtained via self-completion question naire . Results : Dietary records were available for 1026 children at 18 months . A wide variety of drinks were given at this age . In all , 64 % of children had received at least one drink in a bottle and 10 % solely used a bottle . Bottle users consumed a significantly greater volume of milk drinks compared to those who used a cup or other container . The types of drinks consumed and adherence to the guidelines on weaning were associated with several socio-demographic characteristics . In particular , children with mothers of lower educational level were more likely to receive fizzy drinks and low-calorie soft drinks , more likely to drink from a bottle , and less likely to drink from a cup . Conclusion : We have shown that certain groups of mothers with 18-month-old children are not following the current guidelines on weaning . Assuming these guidelines have scientific validity , it is clear that nutritional education needs to be targeted at these mothers to help them feed their children in the optimal way , to protect from nutritional deficiencies , possible later obesity and poor dental health . Sponsorship : University of Bristol OBJECTIVE To assess the prevalence of breastfeeding and formula feeding , the age of introduction to specific foods , and the types of foods and beverages consumed by Hispanic infants and toddlers compared with similarly aged non-Hispanic infants and toddlers living in the United States . DESIGN Descriptive and comparative analysis of dietary recall data and responses to specific interview questions , which were collected in the 2002 Feeding Infants and Toddlers Study . Breastfeeding status , timing of introduction of complementary foods , percentage consuming foods from specific food groups , and the most frequently consumed fruits and vegetables by Hispanic and non-Hispanic children by age group ( 4 - 5 months , 6 - 11 months , 12 - 24 months ) . SUBJECTS A national r and om sample of 371 Hispanic and 2,637 non-Hispanic infants and toddlers between the ages of 4 and 24 months . STATISTICAL ANALYSIS To test for differences between Hispanic and non-Hispanic children in the percentage who consumed a particular food item , we calculated percentages and st and ard errors in SUDAAN and 95 % and 99 % confidence intervals . The most frequently consumed fruits and vegetables were determined by tallying the percentage of infants and toddlers who consumed each specific fruit or vegetable on a given day . RESULTS Although there were some similarities , the early flavor and food experiences of Hispanic infants were different from similarly aged non-Hispanic infants in several ways . Hispanic infants younger than 1 year of age were more likely to have ever been breastfed and those who were 4 to 5 months were more likely than non-Hispanics to be eating pureed baby foods on a daily basis . Although less likely to be eating non-infant cereals and baby food vegetables , 6- to 11-month-old Hispanics were more likely to be eating fresh fruits , fruit-flavored drinks , baby cookies , and foods such as soups , rice , and beans that are common in many Hispanic cultures . When fruits were introduced into the Hispanic child 's diet , they were most commonly consumed fresh . This higher prevalence of being fed soups , rice , beans , and sweetened fruit-flavored drinks as well as tortillas was also observed among the 12- to 24-month-old toddlers . CONCLUSIONS Dietetics professionals should be aware of the cultural differences in the foods fed to infants and toddlers that may contribute to the development of long-term food preferences and impact on nutrition . Underst and ing the factors that underlie food preferences is important if we are to develop evidence -based strategies to improve children 's eating habits and lower their risks factors associated with obesity and other chronic diseases Background Early childhood services have been identified as a key setting for promoting healthy eating and physical activity as a means of preventing overweight and obesity . However , there is limited evidence on effective nutrition and physical activity programs in this setting . The purpose of this study was to evaluate Munch and Move , a low-intensity , state-wide , professional development program design ed to support early childhood professionals to promote healthy eating and physical activity among children in their care . Methods The evaluation involved 15 intervention and 14 control preschools ( n = 430 ; mean age 4.4 years ) in Sydney , New South Wales , Australia and was based on a r and omised-control design with pre and post evaluation of children 's lunchbox contents , fundamental movement skills ( FMS ) , preschool policies and practice s and staff attitudes , knowledge and confidence related to physical activity , healthy eating and recreational screen time . Results At follow up , FMS scores for locomotor , object control and total FMS score significantly improved by 3.4 , 2.1 and 5.5 points more ( respectively ) in the intervention group compared with the control group ( P < 0.001 ) and the number of FMS sessions per week increased by 1.5 ( P = 0.05 ) . The lunchbox audit showed that children in the intervention group significantly reduced sweetened drinks by 0.13 serves ( i.e. , 46 ml ) ( P = 0.05 ) . Conclusion The findings suggest that a low intensity preschool healthy weight intervention program can improve certain weight related behaviours . The findings also suggest that change to food policies are difficult to initiate mid-year and potentially a longer implementation period may be required to determine the efficacy of food policies to influence the contents of preschoolers lunchboxes Foods rich in sugar have been suggested to contribute to the increasing prevalence of obesity in children . The aim of this report is to investigate the dietary pattern in 1-year-old children who frequently receive foods rich in sugar but low in nutrients and to study associated demographic and parental factors . During 1977 - 9 , 21,700 infants were invited to participate in this prospect i ve , population -based , longitudinal cohort study . Screening question naires were completed for 16,070 infants after delivery . Follow-up question naires from 10,762 children at 1 year of age are included in the analysis . It was found that 24 % of the children received sweets/pastries more often than one or two times per week . They had a higher intake of French fries , potato crisps and cream as well as a lower intake of fruit and vegetables . A frequent intake of sugar-rich , low-nutrient foods was significantly associated with several maternal factors ( high intake of sweets/pastries during pregnancy , young age , mother living alone ) as well as presence of older siblings . Maternal smoking during pregnancy and maternal overweight were of borderline significance . Parental education level was inversely associated with the frequency of intake of sweets/pastries in the child . Children who frequently receive sweets/pastries also have an otherwise unfavourable dietary pattern . Several parental and demographic factors were associated with this feeding pattern , especially high intake of sweets/pastries during pregnancy . Screening of pregnant women for risk predictors like consumption of sweets/pastries , young age and smoking could be possible ways of identifying children at future risk for low dietary quality Background / Objectives : This longitudinal study describes the relationship between young children ’s screen time , dietary habits and anthropometric measures . The hypothesis was that television viewing and other screen activities at baseline result in increased consumption of sugar-sweetened beverages ( SSB ) and increased BMI , BMI z-score and waist to height ratio ( WHtR ) two years later . A second hypothesis was that SSB consumption mediates the association between the screen activities and changes in the anthropometric measures .Subjects/ Methods : The study is a part of the prospect i ve cohort study IDEFICS ( “ Identification and prevention of dietary and lifestyle-induced health effects in children and infants ” ) , investigating diet , lifestyle and social determinants of obesity in 2 to 9-year-olds in eight European countries ( baseline n=16 225 , two-year follow-up ; n=11 038 ) . Anthropometry was objective ly measured , and behaviours were parent-reported . Results : The main hypothesis was supported , but the second hypothesis was not confirmed . The odds ratio of being in the highest quintile of % change in WHtR was 1.26 ( 95 % CI : 1.17–1.36 ) and in BMI 1.22 ( 95 % CI : 1.13–1.31 ) , for each hour per day watching television . The odds ratio of having increased SSB consumption was 1.19 ( 95 % CI : 1.09–1.29 ) for each hour per day watching TV . The associations for total screen time were slightly weaker . Conclusions : The results indicate substantial effects of TV viewing and other screen activities for young children , both on their consumption of sugary drinks and on an increase in BMI and central obesity . Our findings suggest that television viewing seems to have a stronger effect on food habits and anthropometry than other screen activities in this age group BACKGROUND AND OBJECTIVE : Although sugar-sweetened beverage ( SSB ) consumption has been tightly linked to weight status among older children , the data regarding these relationships in children aged 2 to 5 years have been mixed . Our objective was to evaluate longitudinal and cross-sectional relationships between SSB consumption and weight status among children aged 2 to 5 years . METHODS : We assessed SSB consumption and BMI z scores among 9600 children followed in the Early Childhood Longitudinal Survey — Birth Cohort , using linear and logistic regression and adjusting for race/ethnicity , socioeconomic status , mother ’s BMI , and television viewing . RESULTS : Higher rates of SSB consumption were associated with higher BMI z scores among children age 4 ( P < .05 ) and 5 ( P < .001 ) but not yet at 2 years . Children aged 5 years who drank SSB regularly ( compared with infrequent/nondrinkers ) had a higher odds ratio for being obese ( 1.43 , confidence interval 1.10–1.85 , P < .01 ) . In prospect i ve analysis , children drinking SSB at 2 years ( compared with infrequent/nondrinkers ) had a greater subsequent increase in BMI z score over the ensuing 2 years ( P < .05 ) . CONCLUSIONS : Similar to what is seen among older children , children aged 2 to 5 years drinking SSB demonstrate both prospect i ve and cross-sectional correlations with higher BMI z score . Pediatricians and parents should discourage SSB consumption to help avoid potential unhealthy weight gain in young children . From a public health st and point , strong consideration should be made toward policy changes leading to decreases in SSB consumption among children BACKGROUND Although the increased prevalence of childhood obesity in the United States has been documented , little is known about its incidence . We report here on the national incidence of obesity among elementary-school children . METHODS We evaluated data from the Early Childhood Longitudinal Study , Kindergarten Class of 1998 - 1999 , a representative prospect i ve cohort of 7738 participants who were in kindergarten in 1998 in the United States . Weight and height were measured seven times between 1998 and 2007 . Of the 7738 participants , 6807 were not obese at baseline ; these participants were followed for 50,396 person-years . We used st and ard thresholds from the Centers for Disease Control and Prevention to define " overweight " and " obese " categories . We estimated the annual incidence of obesity , the cumulative incidence over 9 years , and the incidence density ( cases per person-years ) overall and according to sex , socioeconomic status , race or ethnic group , birth weight , and kindergarten weight . RESULTS When the children entered kindergarten ( mean age , 5.6 years ) , 12.4 % were obese and another 14.9 % were overweight ; in eighth grade ( mean age , 14.1 years ) , 20.8 % were obese and 17.0 % were overweight . The annual incidence of obesity decreased from 5.4 % during kindergarten to 1.7 % between fifth and eighth grade . Overweight 5-year-olds were four times as likely as normal-weight children to become obese ( 9-year cumulative incidence , 31.8 % vs. 7.9 % ) , with rates of 91.5 versus 17.2 per 1000 person-years . Among children who became obese between the ages of 5 and 14 years , nearly half had been overweight and 75 % had been above the 70th percentile for body-mass index at baseline . CONCLUSIONS Incident obesity between the ages of 5 and 14 years was more likely to have occurred at younger ages , primarily among children who had entered kindergarten overweight . ( Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development . ) OBJECTIVE : To assess the effectiveness of a parent-focused intervention on infants ’ obesity-risk behaviors and BMI . METHODS : This cluster r and omized controlled trial recruited 542 parents and their infants ( mean age 3.8 months at baseline ) from 62 first-time parent groups . Parents were offered six 2-hour dietitian-delivered sessions over 15 months focusing on parental knowledge , skills , and social support around infant feeding , diet , physical activity , and television viewing . Control group parents received 6 newsletters on nonobesity-focused themes ; all parents received usual care from child health nurses . The primary outcomes of interest were child diet ( 3 × 24-hour diet recalls ) , child physical activity ( accelerometry ) , and child TV viewing ( parent report ) . Secondary outcomes included BMI z-scores ( measured ) . Data were collected when children were 4 , 9 , and 20 months of age . RESULTS : Unadjusted analyses showed that , compared with controls , intervention group children consumed fewer grams of noncore drinks ( mean difference = –4.45 ; 95 % confidence interval [ CI ] : –7.92 to –0.99 ; P = .01 ) and were less likely to consume any noncore drinks ( odds ratio = 0.48 ; 95 % CI : 0.24 to 0.95 ; P = .034 ) midintervention ( mean age 9 months ) . At intervention conclusion ( mean age 19.8 months ) , intervention group children consumed fewer grams of sweet snacks ( mean difference = –3.69 ; 95 % CI : –6.41 to –0.96 ; P = .008 ) and viewed fewer daily minutes of television ( mean difference = –15.97 : 95 % CI : –25.97 to –5.96 ; P = .002 ) . There was little statistical evidence of differences in fruit , vegetable , savory snack , or water consumption or in BMI z-scores or physical activity . CONCLUSIONS : This intervention result ed in reductions in sweet snack consumption and television viewing in 20-month-old children BACKGROUND Diet in the first 2 y of life may be a pivotal period regarding effects on future blood pressure ( BP ) . However , data on early-life diet and BP in childhood are sparse . OBJECTIVE We prospect ively assessed associations between types of diet spanning infancy and toddlerhood ( ie , transition diets across the complementary feeding period ) and BP at age 7.5 y. DESIGN In a birth cohort study ( Avon Longitudinal Study of Parents and Children ; United Kingdom ) , a total of 1229 children had complete dietary intake data at 6 , 15 , and 24 mo ; BP data at 7.5 y of age ; and all 18 covariables . RESULTS Of the 2 transition diets that were extracted by using principal components analysis , the less-healthy diet was associated with an increase in systolic BP of 0.62 mm Hg ( 95 % CI : 0.00 , 1.24 mm Hg ) and an increase in diastolic BP of 0.55 mm Hg ( 95 % CI : 0.10 , 1.00 mm Hg ) for every one-unit ( SD ) increase in the less-healthy-diet score after adjustment for 15 potential confounders , including maternal characteristics and sociodemographic factors , birth variables , and breastfeeding duration . In contrast with systolic BP , the positive association between the less-healthy transition-diet score and diastolic BP persisted after additional adjustment for child body-size factors [ height , body mass index ( BMI ) , and waist circumference ] at 7.5 y. CONCLUSIONS A less-healthy transition diet by age 2 y was associated with higher BP at 7.5 y. The BMI -related reduction in effect size reinforces the importance of BMI on the diet-BP relation OBJECTIVE To evaluate the impact of a Special Supplemental Nutrition Program for Women , Infants , and Children (WIC)-based intervention on the food and beverage intake , physical activity , and television watching of children ages 1 - 5 . DESIGN Longitudinal surveys of intervention and control participants at baseline , 6 months , and 12 months . RESULTS Analysis of variance tests showed that the intervention had a small but significant impact on TV watching and fruit intake . The intervention was most protective for children younger than 2 years of age . CONCLUSIONS AND IMPLICATION S Although the impact of the intervention was relatively small and limited to the youngest children served by WIC , findings suggest that the WIC setting is appropriate for improving healthful behaviors that are linked to reducing the rates of early childhood overweight OBJECTIVE To examine the effectiveness of a primary care-based obesity intervention over the first year ( 6 intervention contacts ) of a planned 2-year study . DESIGN Cluster r and omized controlled trial . SETTING Ten pediatric practice s , 5 intervention and 5 usual care . PARTICIPANTS Four hundred seventy-five children aged 2 to 6 years with body mass index ( BMI ) in the 95th percentile or higher or 85th to less than 95th percentile if at least 1 parent was overweight ; 445 ( 93 % ) had 1-year outcomes . INTERVENTION Intervention practice s received primary care restructuring , and families received motivational interviewing by clinicians and educational modules targeting television viewing and fast food and sugar-sweetened beverage intake . OUTCOME MEASURES Change in BMI and obesity-related behaviors from baseline to 1 year . RESULTS Compared with usual care , intervention participants had a smaller , nonsignificant change in BMI ( -0.21 ; 95 % confidence interval [ CI ] , -0.50 to 0.07 ; P = .15 ) , greater decreases in television viewing ( -0.36 h/d ; 95 % CI , -0.64 to -0.09 ; P = .01 ) , and slightly greater decreases in fast food ( -0.16 serving/wk ; 95 % CI , -0.33 to 0.01 ; P = .07 ) and sugar-sweetened beverage ( -0.22 serving/d ; 95 % CI , -0.52 to 0.08 ; P = .15 ) intake . In post hoc analyses , we observed significant effects on BMI among girls ( -0.38 ; 95 % CI , -0.73 to -0.03 ; P = .03 ) but not boys ( 0.04 ; 95 % CI , -0.55 to 0.63 ; P = .89 ) and among participants in households with annual incomes of $ 50 000 or less ( -0.93 ; 95 % CI , -1.60 to -0.25 ; P = .01 ) but not in higher-income households ( 0.02 ; 95 % CI , -0.30 to 0.33 ; P = .92 ) . CONCLUSION After 1 year , the High Five for Kids intervention was effective in reducing television viewing but did not significantly reduce BMI Background : To assess whether monthly home visits from trained volunteers could improve infant feeding practice s at age 12 months , a r and omised controlled trial was carried out in two disadvantaged inner city London boroughs . Methods : Women attending baby clinics with their infants ( 312 ) were r and omised to receive monthly home visits from trained volunteers over a 9-month period ( intervention group ) or st and ard professional care only ( control group ) . The primary outcome was vitamin C intakes from fruit . Secondary outcomes included selected macro and micro-nutrients , infant feeding habits , supine length and weight . Data were collected at baseline when infants were aged approximately 10 weeks , and subsequently when the child was 12 and 18 months old . Results : Two-hundred and twelve women ( 68 % ) completed the trial . At both follow-up points no significant differences were found between the groups for vitamin C intakes from fruit or other nutrients . At first follow-up , however , infants in the intervention group were significantly less likely to be given goats ’ or soya milks , and were more likely to have three solid meals per day . At the second follow-up , intervention group children were significantly less likely to be still using a bottle . At both follow-up points , intervention group children also consumed significantly more specific fruit and vegetables . Conclusions : Home visits from trained volunteers had no significant effect on nutrient intakes but did promote some other recommended infant feeding practice s. Trial registration : Current Controlled Trials IS RCT We evaluated the efficacy of a 6-month clinic and home-based behavioral intervention ( Learning about Activity and Underst and ing Nutrition for Child Health ; LAUNCH ) to reduce obesity in preschool children ≥95th BMI percentile compared to enhanced st and ard of care ( Pediatrician Counseling ; PC ) . LAUNCH was a family-based behavioral intervention that taught parents to use child behavior management strategies to increase healthy eating and activity for their children and themselves . PC presented the same diet and activity recommendations , but was delivered in a one-time PC session . Eighteen children aged 2 - 5 years ( mean 4.71 ± 1.01 ) with an average BMI percentile of 98 ( ±1.60 ) and an overweight parent were r and omized to LAUNCH or PC . Assessment s were conducted at baseline , 6 months ( end of LAUNCH treatment ) and 12 months ( 6 months following LAUNCH treatment ) . LAUNCH showed a significantly greater decrease on the primary outcomes of child at month 6 ( post-treatment ) BMI z ( -0.59 ± 0.17 ) , BMI percentile ( -2.4 ± 1.0 ) , and weight gain ( -2.7 kg ± 1.2 ) than PC and this difference was maintained at follow-up ( month 12 ) . LAUNCH parents also had a significantly greater weight loss ( -5.5 kg ± 0.9 ) at month 6 and 12 ( -8.0 kg ± 3.5 ) than PC parents . Based on the data from this small sample , an intensive intervention that includes child behavior management strategies to improve healthy eating and activity appears more promising in reducing preschool obesity than a low intensity intervention that is typical of treatment that could be delivered in primary care In a 4-year follow-up of a r and omized controlled trial , this study aim ed to evaluate the longer-term effects of a peer-led infant feeding intervention that was delivered during the first year of life . The original intervention used monthly home visits from trained volunteers to improve infant feeding practice s among a sample of low-income mothers in two disadvantaged London boroughs . Outcome measures at follow-up included children 's eating and drinking habits , general and dental health , and BMI . Data were collected via structured face-to-face interviews and postal question naires . Of 212 women who completed the original trial , 101 took part in the follow-up ( 55 intervention , 46 control ) . Children 's mean age at follow-up was 4 years 7 months . There is little evidence that the intervention had an important effect on children 's current BMI , caries levels or consumption of fruit and vegetables . However , mothers from the intervention group had better nutritional knowledge and confidence . Intervention group children also consumed more pure fruit juice [ relative risk ( RR ) = 1.57 ; 95 % confidence interval ( CI ) 0.99 , 2.49 ] and were more likely to never drink squash ( RR = 1.76 ; 95 % CI 1.20 , 2.58 ) . The data suggest that the original peer support intervention had a small number of positive long-term effects |
13,515 | 27,935,148 | Both customized and population -based growth charts can identify SGA neonates at risk for adverse outcomes . | OBJECTIVE To compare the effectiveness of customized vs population -based growth charts for the prediction of adverse pregnancy outcomes . | Objectives Construct an ethnic-specific chart and compare the prediction of adverse outcomes using this chart with the clinical ly recommended UK-WHO and customised birth weight charts using cut-offs for small-for-gestational age ( SGA : birth weight < 10th centile ) and large-for-gestational age ( LGA : birth weight > 90th centile ) . Design Prospect i ve cohort study . Setting Born in Bradford ( BiB ) study , UK . Participants 3980 White British and 4448 Pakistani infants with complete data for gestational age , birth weight , ethnicity , maternal height , weight and parity . Main outcome measures Prevalence of SGA and LGA , using the three charts and indicators of diagnostic utility ( sensitivity , specificity and area under the receiver operating characteristic ( AUROC ) ) of these chart-specific cut-offs to predict delivery and neonatal outcomes and a composite outcome . Results In White British and Pakistani infants , the prevalence of SGA and LGA differed depending on the chart used . Increased risk of SGA was observed when using the UK-WHO and customised charts as opposed to the ethnic-specific chart , while the opposite was apparent when classifying LGA infants . However , the predictive utility of all three charts to identify adverse clinical outcomes was poor , with only the prediction of shoulder dystocia achieving an AUROC>0.62 on all three charts . Conclusions Despite being recommended in national clinical guidelines , the UK-WHO and customised birth weight charts perform poorly at identifying infants at risk of adverse neonatal outcomes . Being small or large may increase the risk of an adverse outcome ; however , size alone is not sensitive or specific enough with current detection to be useful . However , a significant amount of missing data for some of the outcomes may have limited the power needed to determine true associations OBJECTIVE : To demonstrate that individualized optimal fetal growth norms , accounting for physiologic and pathologic determinants of fetal growth , better identify normal and abnormal outcomes of pregnancy than existing methods . METHODS : In a prospect i ve cohort of 38,033 singleton pregnancies , we identified 9,818 women with a completely normal outcome of pregnancy and characterized the physiologic factors affecting birth weight using multivariable regression . We used those physiologic factors to individually predict optimal growth trajectory and its variation , growth potential , for each fetus in the entire cohort . By comparing actual birth weight with growth potential , population , ultrasound , and customized norms , we calculated for each fetus achieved percentiles , by each norm . We then compared proportions of pregnancies classified as normally grown , between 10th and 90th percentile , or aberrantly grown , outside this interval , by growth potential and traditional norms , in 14,229 complicated pregnancies , 1,518 pregnancies with diabetes or hypertensive disorders , and 1,347 pregnancies with neonatal complications . RESULTS : Nineteen physiologic factors , associated with maternal characteristics and early placental function , were identified . Growth potential norms correctly classified significantly more pregnancies than population , ultrasound , or customized norms in complicated pregnancies ( 26.4 % compared with 18.3 % , 18.7 % , 22.8 % , respectively , all P<.05 ) , pregnancies with diabetes or hypertensive disorders ( 37.3 % compared with 23.0 % , 28.0 % , 34.0 % , respectively , all P<.05 ) and neonatal complications ( 33.3 % compared with 19.7 % , 24.9 % , 29.8 % , respectively , all P<.05 ) . CONCLUSION : Growth potential norms based on the physiologic determinants of birth weight are a better discriminator of aberrations of fetal growth than traditional norms . LEVEL OF EVIDENCE : BACKGROUND In 2006 , WHO produced international growth st and ards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee . Using the same methods and conceptual approach , the Fetal Growth Longitudinal Study ( FGLS ) , part of the INTERGROWTH-21(st ) Project , aim ed to develop international growth and size st and ards for fetuses . METHODS The multicentre , population -based FGLS assessed fetal growth in geographically defined urban population s in eight countries , in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided . We used ultrasound to take fetal anthropometric measurements prospect ively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction . All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester . The five primary ultrasound measures of fetal growth -- head circumference , biparietal diameter , occipitofrontal diameter , abdominal circumference , and femur length -- were obtained every 5 weeks ( within 1 week either side ) from 14 weeks to 42 weeks of gestation . The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study . FINDINGS We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation , of whom 4607 ( 35 % ) were eligible . 4321 ( 94 % ) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations ( the analysis population ) . We documented very low maternal and perinatal mortality and morbidity , confirming that the participants were at low risk of adverse outcomes . For each of the five fetal growth measures , the mean differences between the observed and smoothed centiles for the 3rd , 50th , and 97th centiles , respectively , were small : 2·25 mm ( SD 3·0 ) , 0·02 mm ( 3·0 ) , and -2·69 mm ( 3·2 ) for head circumference ; 0·83 mm ( 0·9 ) , -0·05 mm ( 0·8 ) , and -0·84 mm ( 1·0 ) for biparietal diameter ; 0·63 mm ( 1·2 ) , 0·04 mm ( 1·1 ) , and -1·05 mm ( 1·3 ) for occipitofrontal diameter ; 2·99 mm ( 3·1 ) , 0·25 mm ( 3·2 ) , and -4·22 mm ( 3·7 ) for abdominal circumference ; and 0·62 mm ( 0·8 ) , 0·03 mm ( 0·8 ) , and -0·65 mm ( 0·8 ) for femur length . We calculated the 3rd , 5th 10th , 50th , 90th , 95th and 97th centile curves according to gestational age for these ultrasound measures , representing the international st and ards for fetal growth . INTERPRETATION We recommend these international fetal growth st and ards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across population s. FUNDING Bill & Melinda Gates Foundation Objective : Compare customized versus population -based growth curves for identification of small-for-gestational-age ( SGA ) and body fat percent ( BF% ) among preterm infants . Methods : Prospect i ve cohort study of 204 preterm infants classified as SGA or appropriate-for-gestational-age ( AGA ) by population -based and customized growth curves . BF% was determined by air-displacement plethysmography . Differences between groups were compared using bivariable and multivariable linear and logistic regression analyses . Results : Customized curves reclassified 30 % of the preterm infants as SGA . SGA infants identified by customized method only had significantly lower BF% ( 13.8 ± 6.0 ) than the AGA ( 16.2 ± 6.3 , p = 0.02 ) infants and similar to the SGA infants classified by both methods ( 14.6 ± 6.7 , p = 0.51 ) . Customized growth curves were a significant predictor of BF% ( p = 0.02 ) , whereas population -based growth curves were not a significant independent predictor of BF% ( p = 0.50 ) at term corrected gestational age . Conclusion : Customized growth potential improves the differentiation of SGA infants and low BF% compared with a st and ard population -based growth curve among a cohort of preterm infants OBJECTIVES Fetal growth restriction is a strong risk factor for stillbirth . We compared the performance of three fetal growth curves - customized , ultrasound ( Hadlock ) and population - in identifying abnormally grown fetuses at risk of stillbirth . METHODS We performed a case-control study of singleton stillbirths ( delivered between 2000 and 2010 ) at one center . Four liveborn controls were r and omly identified for each stillbirth . Ultrasound-estimated fetal weight within 1 month prior to delivery was used to calculate growth percentiles for each fetus using three fetal growth norms . Sensitivities and odds ratios for stillbirth , as well as odds of abnormal growth according to formula , were calculated . RESULTS There were 49 stillbirths and 197 live births . Using the customized norms , growth of the fetuses destined to be stillborn was bimodal , with both more small-for-gestational-age ( SGA ; < 10(th ) percentile ) and large-for-gestational-age ( LGA ; ≥ 90(th ) percentile ) fetuses . Odds of being abnormally grown were significantly higher using ultrasound compared with population norms ( P = 0.02 ) but were not statistically different using ultrasound and customized norms ( P = 0.21 ) . Sensitivity for identification of SGA on ultrasound as a predictor of stillbirth was higher using customized ( 39 % ; 95 % CI , 24 - 54 % ) or ultrasound ( 33 % ; 95 % CI , 19 - 47 % ) , rather than population ( 14 % ; 95 % CI , 4 - 25 % ) , norms . CONCLUSIONS Among fetuses destined to be stillborn , customized and ultrasound norms identified a greater proportion of both SGA and LGA estimated fetal weights . The customized norms performed best in identifying death among SGA fetuses . These results should be interpreted within the limitations of the study design Accurate assessment of fetal growth status requires the definition of an optimal st and ard , which represents the growth potential of the baby . Against this st and ard , individually ' customized ' percentiles can be calculated . They improve the distinction between normal and abnormal , and help in our underst and ing and diagnosis of pathological fetal growth . This method can be used as a tool for epidemiological analysis as well as for prospect i ve clinical monitoring BACKGROUND The recently published INTERGROWTH-21st Project international population st and ard for newborn size is intended for global use , but its ability to identify small infants at risk of adverse outcomes in a general obstetric population has not been reported . OBJECTIVE The objective of the study was to compare adverse neonatal outcomes among small-for-gestational-age ( SGA ) infants between the INTERGROWTH-21st st and ard and a customized birthweight st and ard ( accounting for maternal characteristics of height , weight , parity , and ethnicity ) . We hypothesized that in a multiethnic general obstetric population in Auckl and , New Zeal and , a customized birthweight st and ard would better identify SGA infants at-risk of neonatal morbidity/mortality and stillbirth than the INTERGROWTH-21st st and ard . STUDY DESIGN Using prospect ively gathered maternity data from a general obstetric population in Auckl and , New Zeal and , from 2006 to 2013 ( n = 53,484 births at ≥ 33 weeks ) , infants were classified as SGA ( birthweight < 10th centile ) by INTERGROWTH-21st and customized st and ards . Infants were further categorized as SGA by both criteria , INTERGROWTH-21st only , customized only , or not SGA ( met neither criteria ) . Composite adverse neonatal outcome was defined as neonatal death , neonatal intensive care admission > 48 hours , or ventilation > 4 hours or 5-minute Apgar score < 7 . Relative risks for primary outcomes were estimated using modified Poisson regression , with the non-SGA group as the referent . RESULTS Incidence of SGA was 4.5 % by INTERGROWTH-21st and 11.6 % by customized st and ard . Compared with those not SGA , infants identified as small for gestational age by both criteria had the highest risk of adverse neonatal outcome ( relative risk [ RR ] , 4.1 , 95 % confidence interval [ CI ] , 3.7 - 4.6 ) and stillbirth ( RR , 8.3 , 95 % CI , 5.1 - 13.4 ) . Infants SGA by customized st and ard only ( n = 4015 ) had an increased risk of adverse neonatal outcome ( RR , 2.0 , 95 % CI , 1.8 - 2.2 ) and stillbirth ( RR , 3.0 , 95 % CI , 1.7 - 5.3 ) . Few infants were identified as SGA by INTERGROWTH-21st only ( n = 172 ) , and risks of adverse neonatal outcome and stillbirth were not increased . Findings were unchanged when analyses were limited to term infants ( n = 50,739 ) . The INTERGROWTH-21st st and ard identified more Indian ( 12.8 % ) and Asian ( 5.8 % ) but fewer European ( 3.0 % ) and Pacific ( 2.9 % ) infants as SGA ( P < .01 ) . Customized criteria identified more than 3 times as many SGA infants among Maori ( 14.5 % ) , Pacific ( 13.5 % ) , and European ( 11.2 % ) infants and twice as many among Asian ( 10.3 % ) infants ( P<0.01 ) compared with INTERGROWTH-21st criteria . The majority of SGA infants by INTERGROWTH-21st only were born to Indian and Asian mothers ( 95.4 % ) . CONCLUSIONS In our general obstetric population , birthweight customization identified more SGA infants at risk of perinatal mortality and morbidity compared with the INTERGROWTH-21st st and ard . The INTERGROWTH-21st st and ard failed to detect many at-risk SGA infants , particularly among ethnic groups with larger maternal size while disproportionately identifying higher rates of SGA among those with smaller maternal size . Local validation is needed prior to implementation of the INTERGROWTH-21st st and ard to avoid misclassification of infant birth size |
13,516 | 17,200,327 | In the hierarchy of medical evidence , systematic review s including meta-analyses represent the highest form of evidence if inclusion is limited to Level-I or II studies ( Table I ) . | Evidence -based medicine represents the combination of the best available clinical research evidence with clinical experience and expertise and the needs and expectations of patients .
Evidence -based medicine as a concept has been available for years , but it has become increasingly important over the last decade .
Some evidence has suggested that it began as early as the ancient Chinese medicine practice s , while other evidence has indicated its origins were in postrevolutionary France with the systematic patient observations of Pierre Louis1 .
Gordon Guyatt led a group at McMaster University in the early 1990s that introduced many of the current concepts of evidence -based medicine .
This led to a major increase in interest in the area .
One paper had been published in the literature in 1992 , but by 1998 over a thous and manuscripts had been published in the field1 .
Evidence -based medicine utilizes the best available research evidence .
Systematic review s of Level-III or IV observational studies can be performed , but they represent Level-III or IV evidence . | Sixty consecutive collegiate athletes with “ high ” ankle symptoms were prospect ively evaluated over a 3-year period in an effort to better define this debilitating ankle injury . All athletes included in this study had tenderness over the distal anterior tibiofibular ligament , tenderness proximally along the interosseous membrane , and functional disability . No study subject had a fracture or frank tibia-fibula diastasis . The severity of the sprain was quantified using the interosseous “ tenderness length . ” A st and ard rehabilitation protocol was followed by all patients . Athletes returned to competition when they could perform all functional testing without difficulty . Time to return to full competitive activity averaged 13.4 days . The number of days missed from competition was statistically related to the interosseous tenderness length ( P 0.0001 ) and to positive results on the squeeze test ( P 0.03 ) . Fifty-three of the 60 injured athletes were evaluated at least 6 months after injury . Patients rated their outcomes as good or excellent . Six of the patients experienced occasional ankle pain and stiffness , four patients reported recurrent ankle sprains , and one patient had heterotopic ossification formation Seventy-two patients with subacute or chronic rupture of the anterior cruciate ligament were r and omly assigned to autograft reconstruction with four-str and gracilis and semitendinosus tendon ( N = 37 ) or with patellar tendon-bone ( N = 35 ) from the ipsilateral side . The groups were similar in terms of age , sex , level of activity , degree of laxity , meniscal lesions found surgically , and rehabilitation program . The follow-up was performed at another hospital by independent observers after 6 , 12 , and 24 months . Sixty-one patients ( 32 with hamstring tendon grafts and 29 with patellar tendon grafts ) complied with the follow-up routine for the full 24 months . No differences were found between the groups with respect to Cincinnati functional score , KT-1000 arthrometer measurements , or stairs hopple test results . The subjective result and the single-legged hop test result were better for the hamstring tendon group after 6 and 12 months , but no differences were found after 24 months . The hamstring tendon group showed better isokinetic knee extension strength than did the patellar tendon group after 6 months , but not after 12 and 24 months . There was a significant weakness in isokinetic knee flexion strength among the hamstring tendon group . Anterior knee pain was not significantly different between the groups , but kneeling pain was significantly less common in the hamstring tendon group after 24 months In a two-centre study , 164 patients with unilateral instability of the anterior cruciate ligament were prospect ively r and omised to arthroscopic reconstruction with either a patellar tendon graft using interference screw fixation or a quadruple semitendinosus graft using an endobutton fixation technique . The same postoperative rehabilitation protocol was used for all patients and follow-up at a median of 31 months ( 24 to 59 ) was carried out by independent observers . Four patients ( 2 % ) were lost to follow-up . No significant differences were found between the groups regarding the Stryker laxity test , one-leg hop test , Tegner activity level , Lysholm score , patellofemoral pain score , International Knee Documentation Committee ( IKDC ) score or visual analogue scale , reflecting patient satisfaction and knee function . Slightly decreased extension , compared with the non-operated side , was found in the patellar tendon group ( p < 0.05 ) . Patients with associated meniscal injuries had lower IKDC , visual analogue ( p < 0.01 ) and Lysholm scores ( p < 0.05 ) than those without such injuries . Patients in whom reconstruction had been carried out less than five months after the injury had better final IKDC scores than the more chronic cases ( p < 0.05 ) . We conclude that patellar tendon and quadruple semitendinous tendon grafts have similar outcomes in the medium term . Associated meniscal pathology significantly affects the final outcome and early reconstruction seems to be beneficial The purpose of this study was to examine a young athletic population to up date the data regarding epidemiology and disability associated with ankle injuries . At the United States Military Academy , all cadets presenting with ankle injuries during a 2-month period were included in this prospect i ve observational study . The initial evaluation included an extensive question naire , physical examination , and radiographs . Ankle sprain treatment included a supervised rehabilitation program . Subjects were reevaluated at 6 weeks and 6 months with subjective assessment , physical examination , and functional testing . The mean age for all subjects was 20 years ( range , 17–24 years ) . There were 104 ankle injuries accounting for 23 % of all injuries seen . There were 96 sprains , 7 fractures , and 1 contusion . Of the 96 sprains , 4 were predominately medial injuries , 76 were lateral , and 16 were syndesmosis sprains . Ninety-five percent had returned to sports activities by 6 weeks ; however , 55 % of these subjects reported loss of function or presence of intermittent pain , and 23 % had a decrement of > 20 % in the lateral hop test when compared with the uninjured side . At 6 months , all subjects had returned to full activity ; however , 40 % reported residual symptoms and 2.5 % had a decrement of > 20 % on the lateral hop test . Neither previous injury nor ligament laxity was predictive of chronic symptomatology . Furthermore , chronic dysfunction could not be predicted by the grade of sprain ( grade I vs. II ) . The factor most predictive of residual symptoms was a syndesmosis sprain , regardless of grade . Syndesmosis sprains were most prevalent in collision sports . This study demonstrates that even though our knowledge and underst and ing of ankle sprains and rehabilitation of these injuries have progressed in the last 20 years , chronic ankle dysfunction continues to be a prevalent problem . The early return to sports occurs after almost every ankle sprain ; however , dysfunction persists in 40 % of patients for as long as 6 months after injury . Syndesmosis sprains are more common than previously thought , and this confirms that syndesmosis sprains are associated with prolonged disability Abstract A total of 41 consecutive patients ( 11 women and 30 men , median age 29 ( 18–51 ) years ) with unilateral , isolated , posttraumatic , recurrent anterior shoulder dislocation and a Bankart lesion were operatively repaired , either by an arthroscopic technique including a capsular plication , or by an open procedure with Mitec anchors . All the patients were followed prospect ively and evaluated after a median of 36 ( 30–52 ) months follow-up by a “ blind ” observer . Nineteen patients in each group had excellent or good results , and one in each group was grade d as fair . One patient in the arthroscopic group had a traumatic dislocation 5 months after the operation and was grade d as poor . Three patients experienced subluxations postoperatively , one in the arthroscopic and two in the open group . There was no significant difference in anterior-posterior shoulder laxity measured objective ly with Donjoy . The open Bankart repair group had a statistically significantly longer hospitalization ( P = 0.001 ) , a slight decrease in external range of motion , and more frequent cosmetic complaints . Apart from this , the results revealed no major differences between the two methods after a median of 36 months in this selected group of patients with longst and ing problems PURPOSE The purpose of this study was to compare the results of arthroscopic and open repair of isolated Bankart lesions of the shoulder using metallic suture anchors . TYPE OF STUDY Prospect i ve r and omized clinical study . METHODS Sixty patients with traumatic anterior shoulder instability underwent a surgical repair of an isolated Bankart lesion . The patients were divided into 2 groups of 30 patients each . In group 1 , an arthroscopic repair was performed , and in group 2 , an open procedure was performed . The groups were homogeneous for gender , age , dominance , number of dislocations , time elapsed between first dislocation and surgery , and pathologic findings . In all cases of both groups , the lesion was repaired using metallic suture anchors carrying nonabsorbable braided sutures . Postoperative rehabilitation was the same for the 2 groups . Two years ' follow-up evaluation included Constant and Rowe shoulder scores . Statistical analysis of data was performed using an unpaired t test ( significance for P < .05 ) . RESULTS No recurrence of dislocation of the involved shoulder has been reported in either group . Follow-up Constant and Rowe scores of the 2 groups were not significantly different . The only significant difference seen between the 2 groups was for range of motion evaluation with the Constant score . The mean value for group 1 ( 39.6 + /- 0.8 ) was significantly greater ( P = .017 ) than that for group 2 ( 37.8 + /- 2.0 ) . CONCLUSIONS Arthroscopic repair with suture anchors is an effective surgical technique for the treatment of an isolated Bankart lesion . Open repair does not offer a significantly better 2-year result in terms of stability , and furthermore , can negatively affect the recovery of full range of motion of the shoulder . LEVEL OF EVIDENCE Level BACKGROUND The aim of the study was to compare the results after arthroscopic anterior cruciate ligament ( ACL ) reconstruction using central -third bone-patellar tendon-bone ( BTB ) autografts and triple/quadruple semitendinosus ( ST ) autografts . HYPOTHESIS In the long-term , ACL reconstruction using BTB autografts will render more donor-site problems than ST autografts . STUDY DESIGN R and omized controlled trial ; Level of evidence , 1 . METHODS A r and omized series of 71 patients ( 22 women and 49 men ) with a unilateral ACL rupture who underwent reconstructive surgery were included in the study . The BTB graft was used in 34 patients ( BTB group ) and the ST-tendon graft was used in 37 patients ( ST group ) . The patients were examined a median of 86 months ( range , 68 to 114 months ) after the reconstruction . RESULTS Sixty-eight of 71 patients ( 96 % ) were examined at follow-up . The clinical assessment s at follow-up revealed no significant differences between the BTB group and the ST group in terms of the Lysholm score , Tegner activity level , International Knee Documentation Committee evaluation system , 1-legged hop test , KT-1000 arthrometer laxity measurements , manual Lachman test , and range of motion . A significant improvement was seen in both groups compared with the preoperative values in terms of most clinical assessment s. Donor-site morbidity in the form of knee-walking ability , kneeling ability , and area of disturbed anterior knee sensitivity revealed no significant differences between the groups . CONCLUSION Seven years after ACL reconstruction , the subjective and objective outcomes were similar after using the central -third BTB autograft and triple/quadruple ST autograft . Furthermore , no difference in terms of donor-site morbidity was found between the 2 groups PURPOSE The aim of this study was to compare the results after arthroscopic anterior cruciate ligament ( ACL ) reconstruction using central -third , bone-patellar tendon-bone ( BPTB group ) , 3-str and semitendinosus ( ST group ) , or 4-str and semitendinosus/gracilis ( ST/G group ) autografts . TYPE OF STUDY Prospect i ve r and omized trial . METHODS A r and omized series of 134 patients , all with unilateral ACL rupture was included in the study . In all 3 groups , interference screw fixation of the graft was used at both ends and 125 of 134 ( 93 % ) of the patients returned for the follow-up examination after 26 months ( range , 20 to 43 months ) . The preoperative assessment s in all 3 groups were similar in terms of gender , Tegner activity level , Lysholm score , KT-1000 measurements , 1-leg hop test , and the knee-walking test . RESULTS At follow-up , the knee-walking test was significantly worse in the BPTB group than in the ST group ( P = .0004 ) and ST/G group ( P < .0001 ) . Furthermore , the knee-walking test was significantly worse at follow-up than preoperatively in the BPTB group ( P < .0001 ) . The corresponding findings were not made in the other 2 groups . A significant reduction in knee laxity and an increase in activity level compared with the preoperative assessment s were found in all 3 groups , without any significant differences between the groups . CONCLUSIONS Two years after ACL reconstruction , the use of ST and ST/G autografts rendered significantly less discomfort during the knee-walking test than the use of BPTB autografts . However , in terms of functional outcome and knee laxity , the groups displayed no significant differences . LEVEL OF EVIDENCE Level Seventy patients with patellar tendon or hamstring tendon autografts for single-incision anterior cruciate ligament reconstruction were evaluated at least 2 years after surgery . All reconstructions were performed by the same surgeon , and metal interference screws were used for fixation of all grafts . No significant differences were noted between groups for Lysholm score , reduction in activity , KT-1000 arthrometer findings , quadriceps muscle size , return to sports , or ability to jump and do hard cuts and pivots . Significantly more patients in the patellar tendon group had patellofemoral pain at 6 months after surgery than did the hamstring tendon patients ( 48 % versus 20 % ) , and at last follow-up the incidence of patellofemoral pain was 42 % and 20 % , respectively . Fourteen patients in the patellar tendon group and seven in the hamstring tendon group had loss of motion ( approximately 5 ° ) . Four patients ( two in each group ) had treatment failures and their results were not included in the clinical examination data . At 2 years ’ follow-up , 97 % of patients with patellar tendon grafts and 100 % of patients with hamstring tendon grafts rated their results as good or excellent . We found that hamstring tendon grafts performed similarly to patellar tendon grafts , although fewer patients in the hamstring tendon group had patellofemoral pain and loss of motion One hundred and twenty-seven patients who had a rupture of the anterior cruciate ligament agreed to participate in a prospect i ve , r and omized study of three arthroscopically assisted reconstruction techniques . One hundred and twenty-five patients ( 125 reconstructions ) were evaluated after a mean duration of follow-up of forty-two months ( range , two to five years ) . Group I included forty patients who had a two-incision reconstruction with use of an autogenous semitendinosus-gracilis graft , group II consisted of forty patients who had a two-incision reconstruction with use of an autogenous patellar-ligament graft , and group III included forty-five patients who had a single-incision reconstruction ( endoscopic technique ) with use of an autogenous patellar-ligament graft . The male-female ratio , age range , level of athletic activity , interval between the injury and the reconstruction , previous operative procedures , and associated injuries were similar in all three groups . The same postoperative rehabilitation protocol was followed for all patients . Testing with a KT-2000 arthrometer at maximum manual force was done at the follow-up evaluation ; the difference in laxity between the involved knee and the contralateral knee was three millimeters or less in thirty-three patients ( 83 per cent ) in group I , thirty-seven patients ( 93 per cent ) in group II , and thirty-nine patients ( 87 per cent ) in group III . A difference of two millimeters or less was found in thirty patients ( 75 per cent ) in group I , thirty-one patients ( 78 per cent ) in group II , and thirty-five patients ( 78 per cent ) in group III . Thirty-five patients ( 88 per cent ) in group I , thirty-eight patients ( 95 per cent ) in group II , and forty patients ( 89 per cent ) in group III returned to at least the same level of athletic activity . Four grafts ( two in group I and two in group II ) failed as a result of trauma . There was one additional failure in groups I and III , as evidence d by a difference of nine and seven millimeters , respectively , on instrumented testing of laxity . The significant findings were that no knee was rated D according to the system of the International Knee Documentation Committee ( p < 0.002 , 94 per cent confidence level ) and that fewer additional operative procedures were done on patients in group III ( p < 0.08 ) . Also , it was found that the patients in group II returned to a greater level of athletic activity ( p < 0.02 ) and that a higher percentage of the patients in this group had a difference of three millimeters or less on testing with the KT-2000 arthrometer than in the other two groups ( p < 0.08 ) . However , with the numbers available , there were no significant differences in the over-all outcome among the three groups ( p < 0.1 ) . Importantly , the rate of failure was not greater and the outcomes were not less satisfactory for the late reconstructions than they were for the acute reconstructions ( those performed less than three weeks after the injury ) , including those done with an autogenous semitendinosus-gracilis graft in a chronically unstable knee Background The aim of the study was to compare the results after arthroscopic anterior cruciate ligament ( ACL ) reconstruction using central -third bone — patellar tendon — bone ( BTB ) autografts and triple/quadruple semitendinosus ( ST ) autografts . Hypothesis In the long-term , ACL reconstruction using BTB autografts will render more donor-site problems than ST autografts . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods A r and omized series of 71 patients ( 22 women and 49 men ) with a unilateral ACL rupture who underwent reconstructive surgery were included in the study . The BTB graft was used in 34 patients ( BTB group ) and the ST-tendon graft was used in 37 patients ( ST group ) . The patients were examined a median of 86 months ( range , 68 to 114 months ) after the reconstruction . Results Sixty-eight of 71 patients ( 96 % ) were examined at follow-up . The clinical assessment s at follow-up revealed no significant differences between the BTB group and the ST group in terms of the Lysholm score , Tegner activity level , International Knee Documentation Committee evaluation system , 1-legged hop test , KT-1000 arthrometer laxity measurements , manual Lachman test , and range of motion . A significant improvement was seen in both groups compared with the preoperative values in terms of most clinical assessment s. Donor-site morbidity in the form of knee-walking ability , kneeling ability , and area of disturbed anterior knee sensitivity revealed no significant differences between the groups . Conclusion Seven years after ACL reconstruction , the subjective and objective outcomes were similar after using the central -third BTB autograft and triple/quadruple ST autograft . Furthermore , no difference in terms of donor-site morbidity was found between the 2 groups In 100 consecutive patients with chronic deficiency of the anterior cruciate ligament we reconstructed the ligament using a bone-patellar tendon-bone autograft either with or without a Kennedy ligament augmentation device . The patients had an aggressive rehabilitation programme supervised by two physiotherapists . They were followed prospect ively for at least two years by one surgeon , and assessed after six months and at one and two years . No significant functional or clinical difference was found between the two groups and the stability of the knees did not deteriorate with time in either group . The addition of a Kennedy ligament augmentation device gave no better results than the bone-patellar tendon-bone technique alone Background Bone-patellar tendon-bone graft has been the most commonly used graft material in anterior cruciate reconstructions , but there has been increasing use of hamstring tendon grafts . However , no existing clinical studies show adequate support for the choice of one graft over the other . Hypothesis Hamstring tendons are equally as good as patellar tendon in anterior cruciate ligament reconstructions . Study Design Prospect i ve r and omized clinical trial . Methods Ninety-nine patients with laxity caused by a torn anterior cruciate ligament underwent arthroscopically assisted reconstruction with graft r and omization according to their birth year . Grafts were either bone-patellar tendon-bone with metal interference screw fixation or double-looped hamstring tendons with metal plate fixation . There were no significant differences between the two groups preoperatively or at operation . St and ard rehabilitation included immediate postoperative mobilization without a knee brace , protected weightbearing for 2 weeks , and return to full activity at 6 to 12 months . Results Forty-three patients in the patellar tendon group and 46 patients in the hamstring tendon group were available for clinical evaluation at a minimum of 21 months after surgery . No statistically significant differences were seen with respect to clinical and instrumented laxity testing , International Knee Documentation Committee Score ratings , isokinetic muscle torque measurements , and Kujala patellofemoral , Lysholm , and Tegner scores . Conclusion Equal results were seen for patellar and hamstring tendon autograft anterior cruciate ligament reconstructions at 2 years after surgery . Both techniques seem to improve patients ' performance From 1993 through 1996 , a multicenter study was conducted on the surgical treatment of patients with posttraumatic recurrent anterior shoulder dislocations . Fifty-six patients ( 40 men , 16 women ; mean age 26 years [ range 18 - 51 years ] ) , were evaluated with shoulder arthroscopy . If a Bankart lesion was present , the patients were r and omly allocated to either an arthroscopic reconstruction with the use of biodegradable tacks or an open reconstruction with suture anchors . The postoperative rehabilitation protocol for the two groups was identical . In all patients , the range of shoulder motion , stability , and the Constant and Rowe scores were evaluated at 3 , 12 , and 24 months postoperatively . Thirty patients were surgically treated with the arthroscopic technique and 26 patients with the open technique . In the arthroscopic group , there were recurrences in 7 ( 23 % ) of 30 patients at a mean of 13 months ( range 5 to 21 months ) after surgery . All patients with stable shoulders had a negative apprehension test result . In the open group , there were recurrences in 3 ( 12 % ) of 26 patients at a mean of 10 months ( range 2 to 23 months ) after surgery ( P = not significant ) . In the arthroscopic group , 2 patients had new traumatic redislocations , whereas 1 patient redislocated during an epileptic seizure . In the open group , 1 traumatic redislocation occurred . The 2-year results in this study demonstrate a large number of redislocations after reconstruction , even in the open surgery group . Patient noncompliance with the rehabilitation protocol and predisposing disease may partially explain these results . A tendency was seen toward more redislocations in the arthroscopic group , which emphasizes the importance of correct patient selection and careful surgical technique in the difficult surgical procedure Background : The purpose of this investigation was to evaluate replacement of a torn anterior cruciate ligament with either a bone-patellar tendon-bone autograft or a two-str and semitendinosus-gracilis autograft to compare the results of clinical testing , patient satisfaction , activity level , functional status , and muscle strength . Methods : Fifty-six patients with a torn anterior cruciate ligament were enrolled in a prospect i ve , r and omized , controlled study . Twenty-eight underwent reconstruction with a bone-patellar tendon-bone autograft , and twenty-eight were treated with a two-str and semitendinosus-gracilis autograft . Patients were followed for an average of thirty-nine months ( range , thirty-six to fifty-seven months ) . At the time of final follow-up , twenty-two patients in each group were evaluated in terms of clinical test findings , patient satisfaction , activity level , functional status , and isokinetic muscle strength . Results : The objective outcome of replacement of the torn anterior cruciate ligament with a bone-patellar tendon-bone graft was superior to that obtained with a two-str and semitendinosus-gracilis graft . At the three-year follow-up interval , the patients in whom a hamstring graft had been used had an average of 4.4 mm of increased anterior knee laxity compared with the laxity of the contralateral , normal knee , whereas the patients in whom a bone-patellar tendon-bone graft had been used had an average of 1.1 mm of increased knee laxity . Fourteen percent ( three ) of the twenty-two patients with a hamstring graft had a mild pivot shift , and 27 % ( six ) had a moderate pivot shift . Only 14 % ( three ) of the twenty-two patients with a bone-patellar tendon-bone graft had a mild pivot shift , and none had a moderate pivot shift . At the same follow-up interval , the patients in whom a hamstring graft had been used had significantly lower peak knee-flexion strength than those who had a bone-patellar tendon-bone graft ( p = 0.039 ) . In contrast , the two treatments produced similar outcomes in terms of patient satisfaction , activity level , and knee function ( ability to perform a one-legged hop , bear weight , squat , climb stairs , run in place , and duckwalk ) . Conclusions : After three years of follow-up , the objective results of anterior cruciate ligament replacement with a bone-patellar tendon-bone autograft were superior to those of replacement with a two-str and semitendinosus-gracilis graft with regard to knee laxity , pivot-shift grade , and strength of the knee flexor muscles . However , the two groups had comparable results in terms of patient satisfaction , activity level , and knee function Background Patellar and hamstring tendon autografts are the most frequently used graft types for anterior cruciate ligament reconstruction , but few direct comparisons of outcomes have been published . Hypothesis There is no difference in outcome between the two types of reconstruction . Study Design Prospect i ve r and omized clinical trial . Methods After isolated anterior cruciate ligament rupture , 65 patients were r and omized to receive either a patellar tendon or a four-str and hamstring tendon graft reconstruction , and results were review ed at 4 , 8 , 12 , 24 , and 36 months . Results Pain on kneeling was more common and extension deficits were greater in the patellar tendon group . There were greater quadriceps peak torque deficits in the patellar tendon group at 4 and 8 months but not thereafter . In the hamstring tendon group , active flexion deficits were greater from 8 to 24 months , and KT-1000 arthrometer side-to-side differences in anterior knee laxity at 134 N were greater . Cincinnati knee scores , International Knee Documentation Committee ratings , and rates of return to preinjury activity levels were not significantly different between the two groups . Conclusions Both grafts result ed in satisfactory functional outcomes but with increased morbidity in the patellar tendon group and increased knee laxity and radiographic femoral tunnel widening in the hamstring tendon group One hundred and eleven consecutive patients who had acute injuries to the knee that included rupture of the anterior cruciate ligament , as shown by physical examination with the patient under anesthesia and by diagnostic arthroscopy , were r and omized to three treatment groups : simple repair of all injured structures , repair of all injured structures and augmentation of the anterior cruciate ligament with a strip of the iliotibial b and , and repair of all injured structures except the anterior cruciate ligament . In all other respects , the knees were treated in an identical fashion . Of the 111 patients , 107 were re-examined forty-five months or more after operation . At the most recent follow-up , the knees that had been treated by repair and augmentation of the anterior cruciate ligament were significantly more stable and had had significantly fewer subsequent meniscal tears . Sufficient instability to necessitate late reconstruction was also less frequent in the patients who had had an augmented repair . These patients had better function of the knee and a higher level of activity than the patients in the other two groups . Sixty-four per cent of these patients who had a rupture of the anterior cruciate also had a meniscal tear , and primary care was indicated for more than 50 per cent of the tears . Therefore , we believe that early arthroscopic examination is essential for patients who have an acute rupture of the anterior cruciate ligament |
13,517 | 28,770,272 | Our study demonstrated the effectiveness of anti-osteoporotic agents included in our systematic review in preventing secondary vertebral fractures .
Bisphosphonates and PTH were most effective in preventing non-vertebral fractures . | Patients with osteoporotic fractures have an increased risk for secondary fractures .
However , a rigorous study that assesses the effectiveness of individual osteoporotic drugs in preventing subsequent fractures is lacking .
The purpose of this review was to analyze the effectiveness of anti-osteoporotic drugs in preventing secondary fractures . | Abstract : The purpose of this r and omized , double-masked , placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of vertebral fractures in postmenopausal women with established osteoporosis . The study was conducted at 80 study centers in Europe and Australia . Postmenopausal women ( n= 1226 ) with two or more prevalent vertebral fractures received risedronate 2.5 or 5 mg/day or placebo ; all subjects also received elemental calcium 1000 mg/day , and up to 500 IU/day vitamin D if baseline levels were low . The study duration was 3 years ; however , the 2.5 mg group was discontinued by protocol amendment after 2 years . Lateral spinal radiographs were taken annually for assessment of vertebral fractures , and bone mineral density was measured by dual-energy X-ray absorptiometry at 6-month intervals . Risedronate 5 mg reduced the risk of new vertebral fractures by 49 % over 3 years compared with control ( p<0.001 ) . A significant reduction of 61 % was seen within the first year ( p= 0.001 ) . The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years . The risk of nonvertebral fractures was reduced by 33 % compared with control over 3 years ( p= 0.06 ) . Risedronate significantly increased bone mineral density at the spine and hip within 6 months . The adverse-event profile of risedronate , including gastrointestinal adverse events , was similar to that of control . Risedronate 5 mg provides effective and well-tolerated therapy for severe postmenopausal osteoporosis , reducing the incidence of vertebral fractures and improving bone density in women with established disease Summary To develop an improved treatment schedule for osteoporosis , a study was undertaken in 100 postmenopausal women using a modified ADFR 90-day cyclical regimen with etidronate . After one year of treatment , the etidronate-treated group showed a significant increase in bone density of the spine , which continued over the following 2 years of treatment and remained stable during the fourth year . In contrast , in the non-etidronate group , bone density decreased significantly after four years . In addition , the fracture rate was significantly lower in the etidronate group than in the non-etidronate group . Side effects were minimal in both groups and no serious adverse reactions were reported . In conclusion , it appears that a cyclical regimen using 1,25-dihydroxyvitamin D3 , etidronate and calcium increases bone mass and reduces fractures with no significant side effects , thus making a useful contribution in the treatment of postmenopausal osteoporosis BACKGROUND Risedronate increases bone mineral density in elderly women , but whether it prevents hip fracture is not known . METHODS We studied 5445 women 70 to 79 years old who had osteoporosis ( indicated by a T score for bone mineral density at the femoral neck that was more than 4 SD below the mean peak value in young adults [ -4 ] or lower than -3 plus a nonskeletal risk factor for hip fracture , such as poor gait or a propensity to fall ) and 3886 women at least 80 years old who had at least one nonskeletal risk factor for hip fracture or low bone mineral density at the femoral neck ( T score , lower than -4 or lower than -3 plus a hip-axis length of 11.1 cm or greater ) . The women were r and omly assigned to receive treatment with oral risedronate ( 2.5 or 5.0 mg daily ) or placebo for three years . The primary end point was the occurrence of hip fracture . RESULTS Overall , the incidence of hip fracture among all the women assigned to risedronate was 2.8 percent , as compared with 3.9 percent among those assigned to placebo ( relative risk , 0.7 ; 95 percent confidence interval , 0.6 to 0.9 ; P=0.02 ) . In the group of women with osteoporosis ( those 70 to 79 years old ) , the incidence of hip fracture among those assigned to risedronate was 1.9 percent , as compared with 3.2 percent among those assigned to placebo ( relative risk , 0.6 ; 95 percent confidence interval , 0.4 to 0.9 ; P=0.009 ) . In the group of women selected primarily on the basis of nonskeletal risk factors ( those at least 80 years of age ) , the incidence of hip fracture was 4.2 percent among those assigned to risedronate and 5.1 percent among those assigned to placebo ( P=0.35 ) . CONCLUSIONS Risedronate significantly reduces the risk of hip fracture among elderly women with confirmed osteoporosis but not among elderly women selected primarily on the basis of risk factors other than low bone mineral density We present final results of a study comparing teriparatide 20 μg every day ( QD ) with risedronate 35 mg once per week ( QW ) started within 2 weeks after surgery for a pertrochanteric hip fracture . Patients with BMD T-score ≤ -2.0 and 25OHD ≥9.2 ng/mL were r and omized to receive 26-week double-dummy treatment plus calcium and vitamin D , followed by 52-week open-label treatment with the same assigned active drug . Primary endpoint was change from baseline in lumbar spine ( LS ) BMD at 78 weeks . Secondary and exploratory endpoints were change in BMD at the proximal femur , function , hip pain ( Charnley score and 100 mm Visual Analog Scale [ VAS ] ) , quality of life ( Short Form-36 ) , radiology outcomes , and safety . Data were analyzed with mixed models for repeated measures ( MMRM ) and logistic regression . Totally , 224 patients were r and omized ; 171 ( teriparatide : 86 ) contributed to the efficacy analyses ( mean ± SD age : 77 ± 7.7 years , 77 % females ) . Mean baseline LS , femoral neck ( FN ) , and total hip ( TH ) T-scores were -2.16 , -2.63 , and -2.51 , respectively . At 78 weeks , BMD increased significantly more with teriparatide compared to risedronate at the LS ( + 11.08 % versus + 6.45 % ; p < 0.001 ) and FN ( + 1.96 % versus -1.19 % ; p = 0.003 ) , with no significant between-group difference in TH BMD . Timed up- and -go ( TUG ) test was significantly faster with teriparatide at 6 , 12 , 18 , and 26 weeks ( differences : -3.2 to -5.9 s ; p = 0.045 for overall difference ) . Hip pain during TUG test by 100 mm VAS was significantly lower with teriparatide at 18 weeks ( adjusted difference : -11.3 mm , p = 0.033 ; -10.0 and -9.3 mm at 12 and 26 weeks , respectively ; p = 0.079 for overall difference ) . Other secondary and exploratory outcomes were not different . Teriparatide group showed two new hip fractures versus seven with risedronate ( p = 0.171 ) and more frequent hypercalcemia and hyperuricemia . In conclusion , 78-week treatment with teriparatide showed significantly greater increases in LS and FN BMD , less pain , and a faster TUG test versus risedronate . © 2016 American Society for Bone and Mineral Research Abstract : To examine the risk of mortality following all clinical fractures , we followed 6459 women age 55–81 years participating in the Fracture Intervention Trial for an average of 3.8 years . All fractures and deaths were confirmed by medical record or death certificate . Clinical fractures were fractures that came to medical attention . Fracture status was used as a time-dependent covariate in proportional hazards models . The 907 women who experienced a fracture were older , had lower bone mineral density and were more likely to report a positive fracture history . A total of 122 women died over the course of the study with 23 of these deaths occurring after a clinical fracture . The age-adjusted relative risk ( 95 % confidence intervals ) of dying following a clinical fracture was 2.15 ( 1.36 , 3.42 ) . This primarily reflected the higher mortality following a hip fracture , 6.68 ( 3.08 , 14.52 ) ; and clinical vertebral fracture , 8.64 ( 4.45 , 16.74 ) . Results were similar after adjusting for treatment assignment , health status and specific common comorbidities . There was no increase in mortality following a forearm or other fracture ( non-hip , non-wrist , non-vertebral fracture ) . In conclusion , clinical vertebral fractures and hip fractures are associated with a substantial increase in mortality among a group of relatively healthy older women BACKGROUND Previous studies have shown that alendronate can increase bone mineral density ( BMD ) and prevent radiographically defined ( morphometric ) vertebral fractures . The Fracture Intervention Trial aim ed to investigate the effect of alendronate on the risk of morphometric as well as clinical ly evident fractures in postmenopausal women with low bone mass . METHODS Women aged 55 - 81 with low femoral-neck BMD were enrolled in two study groups based on presence or absence of an existing vertebral fracture . Results for women with at least one vertebral fracture at baseline are reported here . 2027 women were r and omly assigned placebo ( 1005 ) or alendronate ( 1022 ) and followed up for 36 months . The dose of alendronate ( initially 5 mg daily ) was increased ( to 10 mg daily ) at 24 months , with maintenance of the double blind . Lateral spine radiography was done at baseline and at 24 and 36 months . New vertebral fractures , the primary endpoint , were defined by morphometry as a decrease of 20 % ( and at least 4 mm ) in at least one vertebral height between the baseline and latest follow-up radiograph . Non-spine clinical fractures were confirmed by radiographic reports . New symptomatic vertebral fractures were based on self-report and confirmed by radiography . FINDINGS Follow-up radiographs were obtained for 1946 women ( 98 % of surviving participants ) . 78 ( 8.0 % ) of women in the alendronate group had one or more new morphometric vertebral fractures compared with 145 ( 15.0 % ) in the placebo group ( relative risk 0.53 [ 95 % Cl 0.41 - 0.68 ] ) . For clinical ly apparent vertebral fractures , the corresponding numbers were 23 ( 2.3 % ) alendronate and 50 ( 5.0 % ) placebo ( relative hazard 0.45 [ 0.27 - 0.72 ] ) . The risk of any clinical fracture , the main secondary endpoint , was lower in the alendronate than in the placebo group ( 139 [ 13.6 % ] vs 183 [ 18.2 % ] ; relative hazard 0.72 [ 0.58 - 0.90 ] ) . The relative hazards for hip fracture and wrist fracture for alendronate versus placebo were 0.49 ( 0.23 - 0.99 ) and 0.52 ( 0.31 - 0.87 ) . There was no significant difference between the groups in numbers of adverse experiences , including upper-gastrointestinal disorders . INTERPRETATION We conclude that among women with low bone mass and existing vertebral fractures , alendronate is well tolerated and substantially reduces the frequency of morphometric and clinical vertebral fractures , as well as other clinical fractures Abstract Objective : Women without versus those with vertebral fracture may have different benefits and risks during raloxifene treatment . Our objective was to compare the effects of raloxifene to decrease risk for vertebral fracture and invasive breast cancer with its effect to increase risk for venous thromboembolism in postmenopausal women without or with baseline vertebral fracture . Research design and methods : The Multiple Outcomes of Raloxifene Evaluation trial included postmenopausal women with osteoporosis r and omized to placebo , raloxifene 60 mg/day , or raloxifene 120 mg/day for 4 years . The protocol specified subgroups based on whether or not patients had a vertebral fracture at baseline . Absolute differences between placebo and raloxifene 60 mg/day ( the approved dose ) for endpoints in these groups were defined as the incidence in the raloxifene group minus the incidence in the placebo group . Results : Raloxifene decreased the incidence of vertebral fracture and invasive breast cancer while increasing the incidence of venous thromboembolism . All treatment by vertebral fracture status interaction p-values were greater than 0.13 , indicating that the effect of raloxifene on these outcomes was not significantly different between patients without versus those with vertebral fractures . In women without baseline vertebral fracture , absolute risk differences between the raloxifene and placebo group included vertebral fracture −2.83 % , invasive breast cancer −1.21 % , and venous thromboembolism + 0.28 % . In women with baseline vertebral fracture , absolute risk differences between raloxifene and placebo group included vertebral fracture −8.21 % , invasive breast cancer −0.75 % and venous thromboembolism + 0.91 % . The analysis had limited power to test whether raloxifene had a significantly different effect on venous thromboembolism in women without versus those with a vertebral fracture . Conclusions : In women without and in those with vertebral fractures at baseline , the effects of raloxifene to decrease vertebral fracture and invasive breast cancer were greater than its effects to increase venous thromboembolism Summary Intravenous bisphosphonates reduce mortality following hip fracture . We determined whether new use of oral bisphosphonates was also associated with reductions in mortality in 209 hip fracture patients . Oral bisphosphonate exposure led to relative reduction of 8 % per month of use ( p = 0.001 ) or about a 60 % reduction in mortality per year of use . Introduction Intravenous bisphosphonates reduce mortality following hip fracture . Using prospect ively collected long-term data from a r and omized trial of osteoporosis quality improvement for hip fracture , we determined whether new use of oral bisphosphonates was associated with reductions in mortality or the composite outcome of death or new fracture . Methods Originally , 220 hip fracture patients were r and omized to case manager ( n = 110 ) or usual care followed by facilitated bone mineral density ( BMD ) testing ( n = 110 ) interventions . All were eligible for bisphosphonate treatment . Post-r and omization , we followed patients for 3 years and ascertained bisphosphonate treatment , medication adherence and persistence , all-cause mortality , and new clinical fractures . Proportional hazards analyses with time-varying treatment status were undertaken . Results The final study cohort included 209 patients : 136 ( 65 % ) females , 104 ( 50 % ) older than 75 years , 90 ( 43 % ) with poor self-reported health , and 38 ( 18 % ) underweight . Of these , 76 ( 36 % ) had a previous fracture before hip fracture and 132 ( 81 % ) had low BMD . A total of 101 ( 46 % ) patients started oral bisphosphonates and 65 ( 64 % ) remained on treatment at the final evaluation . Overall , 24 ( 11 % ) patients died , 19 ( 9 % ) had new fractures , and 42 ( 20 % ) reached the composite outcome of death or fracture . Compared to no treatment , bisphosphonate exposure was independently associated with reduced mortality ( 17[16 % ] vs. 7[7 % ] ; adjusted hazard ratio ( aHR ) = 0.92 per month treated ; 95%CI , 0.88–0.97 ) and composite endpoints ( 28[26 % ] vs. 5[15 % ] ; aHR = 0.94 per month treated ; 95%CI , 0.91–0.97 ) . Conclusion Like intravenous bisphosphonates after hip fracture , our study suggests that oral bisphosphonates may be associated with reductions in all-cause mortality CONTEXT Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures , but its effects on fracture risk have not been studied for women without vertebral fractures . OBJECTIVE To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density ( BMD ) but no vertebral fractures . DESIGN R and omized , blinded , placebo-controlled trial . SETTING Eleven community-based clinical research centers . SUBJECTS Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less ( Hologic Inc , Waltham , Mass ) but no vertebral fracture ; 4432 were r and omized to alendronate or placebo and 4272 ( 96 % ) completed outcome measurements at the final visit ( an average of 4.2 years later ) . INTERVENTION All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol . Subjects were r and omly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial . MAIN OUTCOME MEASURES Clinical fractures confirmed by x-ray reports , new vertebral deformities detected by morphometric measurements on radiographs , and BMD measured by dual x-ray absorptiometry . RESULTS Alendronate increased BMD at all sites studied ( P<.001 ) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group , but not significantly so ( 14 % reduction ; relative hazard [ RH ] , 0.86 ; 95 % confidence interval [ CI ] , 0.73 - 1.01 ) . Alendronate reduced clinical fractures by 36 % in women with baseline osteoporosis at the femoral neck ( > 2.5 SDs below the normal young adult mean ; RH , 0.64 ; 95 % CI , 0.50 - 0.82 ; treatment-control difference , 6.5 % ; number needed to treat [ NNT ] , 15 ) , but there was no significant reduction among those with higher BMD ( RH , 1.08 ; 95 % CI , 0.87 - 1.35 ) . Alendronate decreased the risk of radiographic vertebral fractures by 44 % overall ( relative risk , 0.56 ; 95 % CI , 0.39 - 0.80 ; treatment-control difference , 1.7 % ; NNT , 60 ) . Alendronate did not increase the risk of gastrointestinal or other adverse effects . CONCLUSIONS In women with low BMD but without vertebral fractures , 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity . Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD OBJECTIVES To determine the efficacy of alendronate treatment on risk of vertebral fracture in a subgroup of women from the Fracture Intervention Trial who had bone mineral density T scores between -1.6 and -2.5 at the femoral neck and to describe how soon after initiation of therapy alendronate becomes effective and whether it is consistent in women with and without existing radiographic vertebral fracture . PATIENTS AND METHODS From May 1992 to March 1997 , postmenopausal women aged 55 to 80 years were r and omized to receive alendronate at 5 mg/d for 2 years and 10 mg/d thereafter or placebo for up to 4.5 years ( mean , 3.8 years ) in a controlled , double-blind , multicenter study . RESULTS A total of 3737 postmenopausal women were included in the study , 1878 in the alendronate group and 1859 in the placebo group . Risk of vertebral fracture was significantly reduced by alendronate compared with placebo for clinical ( relative risk [ RR ] , 0.40 ; 95 % confidence interval [ CI ] , 0.19 - 0.76 ; P=.005 ) and radiographic ( RR , 0.57 ; 95 % CI , 0.41 - 0.81 ; P=-.002 ) fracture . The reductions in vertebral fracture risk were consistent in women with and without an existing radiographic vertebral fracture for clinical ( RR , 0.34 ; 95 % CI , 0.12 - 0.84 ; and RR , 0.46 ; 95 % CI , 0.16 - 1.17 ; respectively ) and radiographic ( RR , 0.53 ; 95 % CI , 0.34 - 0.82 ; and RR , 0.64 ; 95 % CI , 0.38 - 1.10 ; respectively ) fractures . In both groups , the effect of alendronate on clinical vertebral fracture was noted soon after therapy was initiated . The absolute risk of vertebral fracture was low in women without a baseline radiographic fracture . CONCLUSIONS In women with low bone mass who do not meet the bone mineral density criterion for osteoporosis , alendronate is effective in reducing the risk of vertebral fractures . The absolute benefit of this therapy in women with a T score between -1.6 and -2.5 is greater in women with an existing vertebral fracture and /or with other risk factors . The effect of alendronate occurs early The efficacy and safety of oral pamidronate was examined in a double-blind , placebo-controlled trial in women and men with established osteoporosis . Seventy-eight postmenopausal women and 23 men with at least one prevalent vertebral fracture were r and omized separately to 150 mg/day of pamidronate or placebo for 3 years followed by 150 mg/day of pamidronate for an additional 2 years . In addition , all patients received 400 U/day of cholecalciferol and 500 mg/day of elemental calcium . Pamidronate increased significantly bone mineral density of the lumbar spine ( LS-BMD ) and of the femoral neck ( FN-BMD ) . The total increase in BMD of the spine after 5 years of treatment was 14.3 % . Lateral spine radiographs were obtained at baseline and after 3 years of treatment . Fractures of previously normal vertebrae occurred in 15 of 45 patients treated with placebo ( 33.3 % ) and in 5 of 46 patients treated with pamidronate ( 11 % ) . The relative risk was 0.33 ( 95 % CI , 0.14 - 0.77 ) . Treatment was well tolerated and there was no difference in gastrointestinal toxicity between pamidronate and placebo-treated patients . One hundred fifty milligrams daily of pamidronate is an effective and safe treatment of women and men with established osteoporosis CONTEXT There are few published long-term data on absolute risk of subsequent fracture ( refracture ) following initial low-trauma fracture in women and fewer in men . OBJECTIVE To examine long-term risk of subsequent fracture following initial osteoporotic fracture in men and women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study ( Dubbo Osteoporosis Epidemiology Study ) in Australia of 2245 community-dwelling women and 1760 men aged 60 years or older followed up for 16 years from July 1989 through April 2005 . MAIN OUTCOME MEASURE Incidence of first ( initial ) fracture and incidence of subsequent fracture according to sex , age group , and time since first fracture . Relative risk was determined by comparing risk of subsequent fracture with risk of initial fracture . RESULTS There were 905 women and 337 men with an initial fracture , of whom 253 women and 71 men experienced a subsequent fracture . Relative risk ( RR ) of subsequent fracture in women was 1.95 ( 95 % confidence interval [ CI ] , 1.70 - 2.25 ) and in men was 3.47 ( 95 % CI , 2.68 - 4.48 ) . As a result , absolute risk of subsequent fracture was similar in women and men and at least as great as the initial fracture risk for a woman 10 years older . Thus , women and men aged 60 to 69 years had absolute refracture rates of 36/1000 person-years ( 95 % CI , 26 - 48/1000 ) and 37/1000 person-years ( 95 % CI , 23 - 59/1000 ) , respectively . The increase in absolute fracture risk remained for up to 10 years , by which time 40 % to 60 % of surviving women and men experienced a subsequent fracture . All fracture locations apart from rib ( men ) and ankle ( women ) result ed in increased subsequent fracture risk , with highest RRs following hip ( RR , 9.97 ; 95 % CI , 1.38 - 71.98 ) and clinical vertebral ( RR , 15.12 ; 95 % CI , 6.06 - 37.69 ) fractures in younger men . In multivariate analyses , femoral neck bone mineral density , age , and smoking were predictors of subsequent fracture in women and femoral neck bone mineral density , physical activity , and calcium intake were predictors in men . CONCLUSION After an initial low-trauma fracture , absolute risk of subsequent fracture was similar for men and women . This increased risk occurred for virtually all clinical fractures and persisted for up to 10 years Progressive bone loss in osteoporosis results from bone resorption in excess of bone formation . We conducted a double-blind study in 66 women with postmenopausal osteoporosis of therapy with etidronate , a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity . The patients were r and omly assigned in equal numbers to receive oral etidronate ( 400 mg per day ) or placebo for 2 weeks , followed by a 13-week period in which no drugs were given . This sequence was repeated 10 times , for a total of 150 weeks . Daily oral supplementation with calcium and vitamin D was given throughout the study to both groups . Vertebral bone mineral content was measured by dual-photon absorptiometry ; spinal radiographs were assessed to identify new vertebral fractures . Vertebral bone mineral content increased significantly ( P less than 0.01 ) after 150 weeks of etidronate therapy ( 5.3 percent ; 95 percent confidence interval , 2.0 to 8.6 ; n = 20 ) but decreased with placebo ( -2.7 percent ; 95 percent confidence interval , -7.3 to 1.9 ; n = 20 ) . The difference between groups was 8.0 percentage points ( P less than 0.01 ; 95 percent confidence interval , 2.4 to 13.6 ) . The rates of fracture were significantly different for the period from week 60 to week 150 between the etidronate and placebo groups ( 6 vs. 54 fractures per 100 patient-years ; P = 0.023 ) . No adverse clinical , biochemical , or bone histomorphometric effects of treatment were observed . We conclude that at the end of nearly three years , etidronate therapy for postmenopausal osteoporosis results in significant increases in vertebral bone mineral content and , after approximately one year of treatment , a significant decrease in the rate of new vertebral fractures BACKGROUND : Mortality is increased after a hip fracture , and strategies that improve outcomes are needed . METHODS : In this r and omized , double-blind , placebo-controlled trial , 1065 patients were assigned to receive yearly intravenous zoledronic acid ( at a dose of 5 mg ) , and 1062 patients were assigned to receive placebo . The infusions were first administered within 90 days after surgical repair of a hip fracture . All patients received supplemental vitamin D and calcium . The median follow-up was 1.9 years . The primary end point was a new clinical fracture . RESULTS : The rates of any new clinical fracture were 8.6 % in the zoledronic acid group and 13.9 % in the placebo group , a 35 % risk reduction ( P = 0.001 ) ; the respective rates of a new clinical vertebral fracture were 1.7 % and 3.8 % ( P = 0.02 ) , and the respective rates of new nonvertebral fractures were 7.6 % and 10.7 % ( P = 0.03 ) . In the safety analysis , 101 of 1054 patients in the zoledronic acid group ( 9.6 % ) and 141 of 1057 patients in the placebo group ( 13.3 % ) died , a reduction of 28 % in deaths from any cause in the zoledronic-acid group ( P = 0.01 ) . The most frequent adverse events in patients receiving zoledronic acid were pyrexia , myalgia , and bone and musculoskeletal pain . No cases of osteonecrosis of the jaw were reported , and no adverse effects on the healing of fractures were noted . The rates of renal and cardiovascular adverse events , including atrial fibrillation and stroke , were similar in the two groups . CONCLUSIONS : An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and improved survival . ( Clinical Trials.gov number , NCT00046254 . ) Abstract : This paper presents the results of a two-center , double-masked , placebo-controlled , r and omized , oral-dose study of risedronate treatment in postmenopausal osteoporosis . Patients had at least one , but no more than four prevalent vertebral fractures at baseline . They received either 2.5 mg continuous risedronate , 2.5 mg cyclic risedronate , or placebo for 2 years . Both risedronate and placebo were formulated as hard gelatin capsules . All women furthermore received a daily calcium supplement of 1 g which was taken separately from the study drug . During the 1-year of follow-up , all women received only a daily calcium supplement of 1 g. A total of 132 patients were enrolled ( 44 in each treatment group ) , of which 73 % completed the 2-year treatment period and 70 % all 3 years . Generally the outcome of the study was negative . Lumbar spine bone mineral density ( BMD ) increased 1.2 % ( NS ) and 0.8 % ( NS ) and after 2 and 3 years in the group treated with continuous risedronate , 1.7 % ( NS ) and 2.3 % ( p < 0.05 ) in the group treated with cyclic risedronate , and 0.6 % ( NS ) and 1.7 % ( NS ) in the placebo group . BMD in the femoral neck increased 2.9 % ( p < 0.05 ) and 0.9 % ( NS ) after 2 and 3 years in the group treated with continuous risedronate , 1.3 % ( NS ) and 2.4 % ( p < 0.01 ) in the group treated with cyclic risedronate , and 1.3 % ( NS ) and 2.6 % ( p < 0.01 ) in the placebo group . The differences between all three groups in spinal and femoral BMD after 2 years were not statistically significant , bur reached statistical significance after 3 years ( p < 0.01 ) in the femoral neck . Only minor changes were observed in the measured markers of bone turnover . Both the incidence and rate of new vertebral fractures showed no overall differences between the groups . The distribution of adverse events was similar across treatment groups . None of the serious adverse events were considered causally related to risedronate . The lack of effect shown in the present study may be explained by insufficient dose regimen and /or impaired absorption from the intestinal tract . Further investigations ( ongoing phase III trials ) are needed to define future dose regimens in order to vali date the effect on bone mass , fracture rate and biochemical markers . In these studies another formulation of the drug and other dosing instructions are used The purpose of this open , prospect i ve , controlled , r and omized trial was to study the effect of intermittent , cyclic etidronate on the bone mass of osteoporotic postmenopausal women with or without fractures . Eligible subjects were asymptomatic women less than 75 years old who had been amenorrhoeic for at least 1 year . Those with secondary osteoporosis were excluded . Subjects also had to be ambulant with a bone mineral density ( BMD ) of the lumbar spine > 1 SD below that of age matched controls ( Z-score < −1 SD ) . Eighty patients were enrolled , of whom 65 were recruited through a screening programme conducted in the practice s of two general practitioners . The remaining patients were from other referrals . The subjects were r and omized to two groups of 40 women . Treatment regimens were as follows . The etidronate group was treated with etidronate 400 mg once daily for 14 days followed by 76 days of 500 mg of elementary calcium once daily ; this cycle was repeated every 3 months . The calcium group took 500 mg of elementary calcium once daily . The groups were not different in age , height , weight , time since menopause , BMD at baseline and prevalent vertebral fractures . In 50 patients ( 28 in the etidronate group and 22 in the calcium group ) no vertebral fractures were present ( 67 % ) . Sixty-four patients ( 35 in the etidronate group and 29 in the calcium group ) completed the 3 years of the study . In the etidronate group the mean BMD of the lumbar spine , femoral neck , trochanter and Ward 's triangle increased by 5.7 % , 1.4 % , 7.1 % and 10.9 % from baseline values respectively ( p<0.05 at all sites except for the femoral neck ) . In the calcium group no significant changes from baseline were found at any time point at any site after 3 years , except for the femoral neck , where BMD at 156 weeks decreased significantly by 3 % ( p<0.003 ) . In 3 patients , all in the calcium group , six new fractures were found . There were no serious adverse effects . We conclude that intermittent , cyclic treatment with etidronate causes a significant increase in the BMD of the lumbar spine and the proximal femur in osteopenic postmenopausal women , and that treatment is safe and has no serious adverse effects BACKGROUND Small increases in bone mass are commonly seen with existing treatments for osteoporosis , which reduce bone remodelling and primarily prevent bone loss . Since these drugs reduce but do not eliminate risk of fractures , an anabolic agent that would increase bone mass and potentially cure the underlying skeletal problem is needed . METHODS We did a 3-year r and omised controlled trial to find out the effects of 1 - 34 human parathyroid hormone ( hPTH [ 1 - 34 ] , 400 U/25 micrograms daily subcutaneously ) in postmenopausal women with osteoporosis taking hormone-replacement therapy ( n = 17 ) . The controls were women taking hormone-replacement therapy only ( n = 17 ) . The primary outcome was bone-mineral density of the lumbar vertebrae , with bone-mineral density at other sites and vertebral fractures as secondary endpoints . FINDINGS Patients taking hormone-replacement therapy and PTH ( 1 - 34 ) had continuous increase in vertebral bone-mineral density during the 3 years , whereas there was no significant change in the control group . The total increase in vertebral bone-mineral density was 13.0 % ( p < 0.001 ) ; 2.7 % at the hip ( p = 0.05 ) ; and 8.0 % in total-body bone mineral ( p = 0.002 ) . No loss of bone mass was found at any skeletal site . Increased bone mass was associated with a reduction in the rate of vertebral fractures , which was significant when fractures were taken as a 15 % reduction in vertebral height ( p = 0.04 ) . During the first 6 months of treatment , serum osteocalcin concentration , which reflects bone formation , increased by more than 55 % , whereas excretion of crosslinked n-telopeptide , which reflects bone resorption , increased by only 20 % , which suggests some uncoupling of bone formation and resorption . By 6 months , there were similar increases in both markers , which gradually returned towards baseline as the study progressed . Vertebral bone-mineral density increased most during the first year of PTH treatment . INTERPRETATION We found that PTH has a pronouned anabolic effect on the central skeleton in patients on hormone-replacement therapy . PTH also increases total-body bone mineral , with no detrimental effects at any skeletal site . The increased vertebral mass was associated with a reduced rate of vertebral fracture , despite increased bone turnover . Bone-mass changes may be consistent with a reduction in all osteoporotic fractures . If confirmed in larger studies , these data have important implication s for the treatment of postmenopausal osteoporosis PURPOSE We conducted a 5-year , double-blind , r and omized , placebo-controlled study to determine whether salmon calcitonin nasal spray reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis . SUBJECTS AND METHODS A total of 1,255 postmenopausal women with established osteoporosis were r and omly assigned to receive salmon calcitonin nasal spray ( 100 , 200 , or 400 IU ) or placebo daily . All participants received elemental calcium ( 1,000 mg ) and vitamin D ( 400 IU ) daily . Vertebral fractures were assessed with lateral radiographs of the spine . The primary efficacy endpoint was the risk of new vertebral fractures in the salmon calcitonin nasal spray 200-IU group compared with the placebo group . RESULTS During 5 years , 1,108 participants had at least one follow-up radiograph . A total of 783 women completed 3 years of treatment , and 511 completed 5 years . The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33 % compared with placebo [ 200 IU : 51 of 287 , placebo : 70 of 270 , relative risk ( RR ) = 0.67 , 95 % confidence interval ( CI ) : 0.47- to 0.97 , P = 0.03 ] . In the 817 women with one to five prevalent vertebral fractures at enrollment , the risk was reduced by 36 % ( RR = 0.64 , 95 % CI : 0.43- to 0.96 , P = 0.03 ) . The reductions in vertebral fractures in the 100-IU ( RR = 0.85 , 95 % CI : 0.60- to 1.21 ) and the 400-IU ( RR = 0.84 , 95 % CI : 0.59- to 1.18 ) groups were not significantly different from placebo . Lumbar spine bone mineral density increased significantly from baseline ( 1 % to 1 . 5 % , P<0.01 ) in all active treatment groups . Bone turnover was inhibited , as shown by suppression of serum type-I collagen cross-linked telopeptide ( C-telopeptide ) by 12 % in the 200-IU group ( P < 0.01 ) and by 14 % in the 400-IU group ( P<0.01 ) as compared with placebo . CONCLUSION Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis Animal experiments show a dramatic improvement in skeletal repair by teriparatide . We tested the hypothesis that recombinant teriparatide , at the 20 microg dose normally used for osteoporosis treatment or higher , would accelerate fracture repair in humans . Postmenopausal women ( 45 to 85 years of age ) who had sustained a dorsally angulated distal radial fracture in need of closed reduction but no surgery were r and omly assigned to 8 weeks of once-daily injections of placebo ( n = 34 ) or teriparatide 20 microg ( n = 34 ) or teriparatide 40 microg ( n = 34 ) within 10 days of fracture . Hypotheses were tested sequentially , beginning with the teriparatide 40 microg versus placebo comparison , using a gatekeeping strategy . The estimated median time from fracture to first radiographic evidence of complete cortical bridging in three of four cortices was 9.1 , 7.4 , and 8.8 weeks for placebo and teriparatide 20 microg and 40 microg , respectively ( overall p = .015 ) . There was no significant difference between the teriparatide 40 microg versus placebo groups ( p = .523 ) . In post hoc analyses , there was no significant difference between teriparatide 40 microg versus 20 microg ( p = .053 ) ; however , the time to healing was shorter in teriparatide 20 microg than placebo ( p = .006 ) . The primary hypothesis that teriparatide 40 microg would shorten the time to cortical bridging was not supported . The shortened time to healing for teriparatide 20 microg compared with placebo still may suggest that fracture repair can be accelerated by teriparatide , but this result should be interpreted with caution and warrants further study BACKGROUND Mortality is increased after a hip fracture , and strategies that improve outcomes are needed . METHODS In this r and omized , double-blind , placebo-controlled trial , 1065 patients were assigned to receive yearly intravenous zoledronic acid ( at a dose of 5 mg ) , and 1062 patients were assigned to receive placebo . The infusions were first administered within 90 days after surgical repair of a hip fracture . All patients ( mean age , 74.5 years ) received supplemental vitamin D and calcium . The median follow-up was 1.9 years . The primary end point was a new clinical fracture . RESULTS The rates of any new clinical fracture were 8.6 % in the zoledronic acid group and 13.9 % in the placebo group , a 35 % risk reduction with zoledronic acid ( P=0.001 ) ; the respective rates of a new clinical vertebral fracture were 1.7 % and 3.8 % ( P=0.02 ) , and the respective rates of new nonvertebral fractures were 7.6 % and 10.7 % ( P=0.03 ) . In the safety analysis , 101 of 1054 patients in the zoledronic acid group ( 9.6 % ) and 141 of 1057 patients in the placebo group ( 13.3 % ) died , a reduction of 28 % in deaths from any cause in the zoledronic acid group ( P=0.01 ) . The most frequent adverse events in patients receiving zoledronic acid were pyrexia , myalgia , and bone and musculoskeletal pain . No cases of osteonecrosis of the jaw were reported , and no adverse effects on the healing of fractures were noted . The rates of renal and cardiovascular adverse events , including atrial fibrillation and stroke , were similar in the two groups . CONCLUSIONS An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and with improved survival . ( Clinical Trials.gov number , NCT00046254 [ Clinical Trials.gov ] . ) There is a need for effective and acceptable therapies for postmenopausal osteoporosis . The bisphosphonates show promise in this role , but the effects of the potent bisphosphonates in established osteoporosis have not yet been reported . We performed a 2-yr , r and omized , double blind , placebo-controlled trial of pamidronate ( 150 mg/day ) in 48 postmenopausal osteoporotic women . Bone mineral density of the total body , lumbar spine , and proximal femur was measured every 6 months by dual energy x-ray absorptiometry . Bone mineral density increased progressively in the total body ( 1.9 + /- 0.7 % ; P < 0.01 ) , lumbar spine ( 7.0 + /- 1.0 % ; P < 0.0001 ) , and femoral trochanter ( 5.4 + /- 1.3 % ; P < 0.001 ) in subjects receiving pamidronate , but did not change significantly in those receiving placebo . There were significant decreases in bone density at both the femoral neck ( P < 0.02 ) and Ward 's triangle ( P < 0.01 ) in subjects taking placebo , which did not occur in the pamidronate group . The differences between the treatment groups were significant at all sites ( 0.0001 < P < 0.05 ) except Ward 's triangle . Vertebral fracture rates were 13/100 patient yr in the pamidronate group and 24/100 patient yr in those receiving placebo ( P = 0.07 ) , and there was a nonsignificant trend toward height loss being less in those receiving pamidronate ( P = 0.16 ) . It is concluded that pamidronate is an effective therapy in postmenopausal osteoporosis Prevalent vertebral fractures and baseline bone mineral density ( BMD ) predict subsequent fracture risk . The objective of this analysis is to examine whether baseline vertebral fracture severity can predict new vertebral and nonvertebral fracture risk . In the r and omized , double-blind 3-year Multiple Outcomes of Raloxifene Evaluation ( MORE ) trial , 7705 postmenopausal women with osteoporosis ( low BMD or prevalent vertebral fractures ) were r and omly assigned to placebo , raloxifene 60 mg/day , or raloxifene 120 mg/day . Post hoc analyses studied the association between baseline fracture severity and new fracture risk in the placebo group and the effects of placebo , raloxifene 60 mg/day , and raloxifene 120 mg/day on new fracture risk in women with the most severe prevalent vertebral fractures ( n = 614 ) . Vertebral fracture severity was visually assessed using semiquantitative analysis of radiographs and categorized by estimated decreases in vertebral heights . Reported new nonvertebral fractures were radiographically confirmed . Baseline vertebral fracture severity predicted vertebral and nonvertebral fracture risk at 3 years . In women without prevalent vertebral fractures , 4.3 and 5.5 % had new vertebral and nonvertebral fractures , respectively . In women with mild , moderate , and severe prevalent vertebral fractures , 10.5 , 23.6 , and 38.1 % respectively had new vertebral fractures , whereas 7.2 , 7.7 , and 13.8 % respectively experienced new nonvertebral fractures . Number of prevalent vertebral fractures and baseline BMD also predicted vertebral fracture risk , but the severity of prevalent vertebral fractures was the only predictor of nonvertebral fracture risk and remained a significant predictor after adjustment for baseline characteristics , including baseline BMD . In patients with severe baseline vertebral fractures , raloxifene 60 mg/day decreased the risks of new vertebral [ RR 0.74 ( 95 % Cl 0.54 , 0.99 ) ; P = 0.048 ] and nonvertebral ( clavicle , humerus , wrist , pelvis , hip , and leg ) fractures [ RH 0.53 ( 95 % CI 0.29 , 0.99 ) ; P = 0.046 ] at 3 years . To prevent one new fracture at 3 years in women with severe baseline vertebral fractures with raloxifene 60 mg/day , the number needed to treat ( NNT ) was 10 for vertebral and 18 for nonvertebral fractures . Similar results were observed in women receiving raloxifene 120 mg/day . In summary , baseline vertebral fracture severity was the best independent predictor for new vertebral and nonvertebral fracture risk . Raloxifene decreased new vertebral and nonvertebral fracture risk in the subgroup of women with severe vertebral fractures at baseline . These fractures may reflect architectural deterioration , independent of BMD , leading to increased skeletal fragility The aim of this study was to examine the effects of risedronate ( 5 mg/daily ) in patients identified solely on the basis of a prior fragility fracture , without BMD as an inclusion criterion . A total of 1,802 patients were examined from the VERT-NA and VERT-MN clinical trials . Lateral radiographs ( T4 to L4 ) were obtained at baseline and annually ; incident fractures were evaluated using quantitative and semiquantitative methods at the central facility . BMD was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry . Secondary analyses evaluated vertebral fracture efficacy in patient subgroups categorized according to the presence of risk factors for osteoporosis at baseline ( age , femoral neck BMD , lumbar spine BMD , more severe BMD , height , weight , body mass index , prevalent nonvertebral fracture status , smoking , and bone turnover marker levels ) . Over 3 years , risedronate reduced the risk of new vertebral fractures by 44 % ( 95 % CI , 28 % to 56 % ) compared with placebo . In patients subgrouped according to the presence or absence of putative risk factors , the efficacy of risedronate was comparable across all groups ( all treatment-by-non BMD subgroup interactions p≥0.210 ) . Adjustment for age , baseline BMD , and prevalent vertebral fractures on fracture risk gave results similar to the unadjusted analysis . In patients taking placebo , the incidence of new vertebral fracture was higher in several of the high-risk categories ( elderly , T-score ≤−2.5 SD ) . In conclusion , the findings of this study suggest that risedronate is effective in patients identified solely on the basis of a prior fragility fracture and that the efficacy of risedronate in the reduction of vertebral fractures is largely independent of the presence of clinical risk factors for osteoporotic fracture PURPOSE Hormone replacement therapy ( HRT ) with estrogen and treatment with bisphosphonates have been shown to increase bone mineral density ( BMD ) in postmenopausal women . This 4-year prospect i ve r and omized study was carried out to assess the effectiveness of the combined HRT plus etidronate on BMD in postmenopausal women with established osteoporosis . PATIENTS AND METHODS Seventy-two postmenopausal women ( mean age 64.9+/-0.5 years ) attending metabolic bone disease outpatient clinics with established osteoporosis were r and omly allocated into one of four treatment groups and monitored for 4 years . All patients enrolled in this study including the control group ( n=18 ) received 1.0 g elemental calcium and 400 units vitamin D per day . The HRT group ( n=18 ) received cyclical estrogen and progesterone ; the etidronate group ( n=17 ) received intermittent cyclical etidronate ; and the combined therapy group ( n=19 ) received both HRT and etidronate . BMD was measured in the lumbar spine and the hip before treatment and at 2 and 4 years after treatment . Changes in height were recorded , and the occurrence of new vertebral fractures were documented in comparison with the baseline radiographic evaluation . In 40 patients ( 10 patients per group ) , analysis of bone histomorphometry was carried out after 4 years of treatment . RESULTS In patients who received the combined therapy , BMD increased in the lumbar spine by 10.4 % ( P < 0.001 ) and in the hip by 7.0 % ( P < 0.001 ) at 4 years . For patients treated with ICE , these increases were 7.3 % ( P < 0.001 ) and 0.9 % ( P < 0.05 ) , and with HRT , the increases were 7.0 % ( P < 0.001 ) and 4.8 % ( P < 0.01 ) in the vertebrae and femora , respectively . The group treated with calcium and vitamin D lost 2.5 % ( P < 0.05 ) and 4.4 % ( P < 0.01 ) of BMD in the vertebrae and femora , respectively , after 4 years . Patients who received combined therapy had significantly higher BMD in both the vertebrae and in the femora ( P < 0.05 ) in comparison with patients who were treated with HRT or etidronate alone after 4 years . In comparison with patients in the control group , there was a trend toward a lower rate of new vertebral fractures in the treatment groups . Height loss was significantly less in all three active treatment groups ( HRT [ P < 0.001 ] , etidronate [ P < 0.02 ] , and combined therapy group [ P < 0.0001 ] ) , in comparison with the control group . The combined therapy group did not have a significant height loss , in comparison with the HRT ( P < 0.02 ) and the etidronate ( P < 0.001 ) groups . None of the patients had histomorphometric evidence of osteomalacia . CONCLUSION This 4-year r and omized study showed an additive effect of etidronate and HRT on hip and spine BMD in postmenopausal women with established osteoporosis BACKGROUND Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia , but their effects on fractures are unknown . METHODS We r and omly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of parathyroid hormone ( 1 - 34 ) or placebo , administered subcutaneously by the women daily . We obtained vertebral radiographs at base line and at the end of the study ( median duration of observation , 21 months ) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry . RESULTS New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent , respectively , of the women in the 20-microg and 40-microg parathyroid hormone groups ; the respective relative risks of fracture in the 20-microg and 40-microg groups , as compared with the placebo group , were 0.35 and 0.31 ( 95 percent confidence intervals , 0.22 to 0.55 and 0.19 to 0.50 ) . New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group ( relative risk , 0.47 and 0.46 , respectively [ 95 percent confidence intervals , 0.25 to 0.88 and 0.25 to 0.861 ) . As compared with placebo , the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck ; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points . Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo . Parathyroid hormone had only minor side effects ( occasional nausea and headache ) . CONCLUSIONS Treatment of postmenopausal osteoporosis with parathyroid hormone ( 1 - 34 ) decreases the risk of vertebral and nonvertebral fractures ; increases vertebral , femoral , and total-body bone mineral density ; and is well tolerated . The 40-microg dose increased bone mineral density more than the 20-microg dose but had similar effects on the risk of fracture and was more likely to have side effects Objectives A history of prior fracture is one of the strongest predictors of a future fragility fracture . In FREEDOM , denosumab significantly reduced the risk of new vertebral , non-vertebral , and hip fractures . We carried out a post-hoc analysis of FREEDOM to characterize the efficacy of denosumab in preventing secondary fragility fractures in subjects with a prior fracture . Methods A total of 7808 women aged 60–90 years with a bone mineral density T-score of less than − 2.5 but not less than − 4.0 at either the lumbar spine or total hip were r and omized to subcutaneous denosumab 60 mg or placebo every 6 months for 36 months . The anti-fracture efficacy of denosumab was analyzed by prior fracture status , to assess secondary fragility fracture , and by subject age , prior fracture site and history of prior osteoporosis medication use . Results A prior fragility fracture was reported for 45 % of the overall study population . Compared with placebo , denosumab significantly reduced the risk of a secondary fragility fracture by 39 % ( incidence , 17.3 % vs. 10.5 % ; p < 0.0001 ) . Similar results were observed regardless of age or prior fracture site . In the overall population , denosumab significantly reduced the risk of a fragility fracture by 40 % ( 13.3 % vs. 8.0 % ; p < 0.0001 ) , with similar results observed regardless of history of prior osteoporotic medication use . Conclusions Denosumab reduced the risk of fragility fractures to a similar degree in all risk subgroups examined , including those with prior fragility fractures . Identifying and treating high-risk individuals could help to close the current care gap in secondary fracture prevention |
13,518 | 18,254,045 | Given that haloperidol and chlorpromazine are global st and ard antipsychotic treatments for schizophrenia , it is surprising that less than 800 people have been r and omised to a comparison and that incomplete reporting still makes it difficult for anyone to draw clear conclusions on the comparative effects of these drugs .
However , it seems that haloperidol causes more movement disorders than chlorpromazine , while chlorpromazine is significantly more likely to lead to hypotonia . | BACKGROUND Chlorpromazine and haloperidol are benchmark antipsychotic drugs .
Both are said to be equally effective when used at equivalent doses , but have different side-effect profiles .
OBJECTIVES To compare the effects of haloperidol and chlorpromazine for people with schizophrenia and schizophrenia-like psychoses . | Poor neuroleptic response is a major unresolved clinical problem . Precise data concerning the frequency of poor neuroleptic response are not available . The implementation of treatment modalities that are specifically recommended for non‐responders ( such as clozapine ) increases the desirability of such data . This study evaluated the proportion of acutely exacerbated schizophrenics who remained unimproved by consecutive administration of haloperidol , chlorpromazine and perphenazine , in r and omly determined order . The overall improvement rate was 95 % . The frequency of good responses to the first , second and third drug were 67 % , 55 % , and 67 % respectively . Differences in receptor affinity profile might explain the added beneficial effect of a second or third drug The relative efficacy of 4 tranquilizers was investigated in 66 chronic schizophrenics who had been hospitalized for 10.01 years ( mean ) . The role of adding an anti-depressant was also studied . Following a 4 week placebo period , high dosage tranquilizers were given for 16 weeks and amitriptyline was added for the following 16 weeks . Statistical analyses of the various change measures revealed that patients worsened significantly on placebo , all 4 tranquilizers were significantly better than placebo for symptom reduction and maximum improvement was attained within 16 weeks of tranquilizer administration . No significant differences in efficacy were observed among the 4 tranquilizers and addition of amitriptyline did not confer any additional therapeutic advantage The results of a prospect i ve study on the incidence of thrombocytopenia in matched psychiatric in patients receiving different antipsychotics are reported . Patients were receiving haloperidol ( N = 159 ) , chlorpromazine ( N = 164 ) , fluphenazine decanoate ( N = 152 ) , or no drug therapy ( control , N = 102 ) . The groups did not differ statistically in respect to the incidence of thrombocytopenia , mean platelet levels , age , chlorpromazine equivalent dosages , or duration of drug therapy ( p > 0.05 ) . The two phenothiazine-treated groups had significantly higher numbers of patients with lownormal platelet levels when compared to both the haloperidol and control groups ( p < 0.05 ) . Also , a nonsignificant trend was noted for increased incidence of thrombocytopenia among the phenothiazine groups compared with the haloperidol and control groups . Upon retrospective analysis of preneuroleptic treatment platelet levels , significant decreases in platelet values were observed with the phenothiazine-treated patients ( p < 0.001 ) , but not with haloperidol ( p > 0.05 ) . The results indicate that neuroleptic drug-induced thrombocytopenia is rare but may be more common with phenothiazine antipsychotics The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas The effectiveness of injectable chlorpromazine was compared with the effectiveness of injectable haloperidol with highly agitated , acute psychotic patients and chronic patients with acute exacerbations . While both groups improved , haloperidol effected a significantly greater improvement in patients 40 years of age or older than did chlorpromazine . This result is consistent with those reported in other studies In a double-blind , cross-over study , the comparative therapeutic effects of 6-week courses of two prototypic neuroleptics — haloperidol and chlorpromazine — and the reversal of those effects with benztropine were investigated in a group of 18 schizophrenics . Periodic measurements were made for 32 dimensions of psychopathology , social participation , span of attention , sleeplessness , pulse rate and neurological side effects . The results showed that haloperidol was generally a more effective drug over the period studied . This was particularly apparent in terms of social and emotional responsiveness , communicativeness and cognitive processes . The only superiority of chlorpromazine seemed to be that patients felt less dysphoric on it than they did on haloperidol . Haloperidol also proved to be more rapid in its action . The data failed to support the clinical validity of the distinction often made between “ sedative ” and “ activating ” neuroleptics . Consistent with previous reports , benztropine had the effect of diminishing therapeutic response to both neuroleptics . However , haloperidol again proved less susceptible to this effect . The slowness and lesser therapeutic efficiency of chlorpromazine and its greater susceptibility to benztropine reversal were all considered to be due to its built-in anticholinergic properties acting in opposition to its antipsychotic activity . The low potency of chlorpromazine-like drugs was attributed to their inherent anticholinergic characteristics . It was suggested that one of the factors determining potency differences among neuroleptics may be the degree of built-in anticholinergic activity A study of anti‐Parkinsonism agents in prolonged phenothiazine therapy seeks to clarify some anecdotal misconceptions . Antiparkinsonian agents do not appear to affect the therapeutic efficiency of phenothiazines , nor does using them on a “ dem and ” basis increase the problems of control of parkinsonian side effects . Older patients , however , appear to require the extended usage of antiparkinsonian agents rather more than some studies would suggest . Sustained release antiparkinsonian agents may yet further simplify the management of schizophrenia A study design ed to assess the relative efficacy of chlorpromazine and Serenace in the control of chronic schizophrenics is described . Twenty-five cases were selected for the study and were r and omly allocated to treatment . The condition of the patients was assessed at fortnightly intervals over the eight-week duration of trial period . No significant differences in side-effects emerged in patients on chlorpromazine and Serenace in the dosages administered . The statistically significant trends all showed a superiority of Serenace above chlorpromazine which was in accord with the clinical picture The schizophrenic patient 's early psychological response to neuroleptic treatment has been demonstrated to be a significant predictor of treatment response . The validity of the construct of subjective response is evaluated by comparison of two measures . Fifty-five recently admitted and unmedicated schizophrenic patients were r and omly allocated to chlorpromazine or haloperidol . Subjective responses at 24 and 48 hours as assessed by two different scales , the Van Putten & May scale and the self-administered Drug Attitude Inventory , were strongly correlated with outcome at three weeks . Early emergence of extrapyramidal symptoms was not related to subjective response , but dysphoric patients had a greater incidence of EPS by the end of treatment than did non-dysphoric patients . The two measures showed high concordance in identification of early drug dysphoria In this paper we have described early applications of computerized EEG techniques in psychopharmacology . Perhaps our most remarkable finding was there were practically no differences between very chronic drug free schizophrenic patients and normals , which contradicts much of the EEG imaging literature . To us , the most likely explanation is that most of the anterior slowing observed in other studies was due to contamination from orbital artifacts , which we took exceptional pains to remove . Lingering effects of neuroleptic medications may also have contributed . Alternatively , EEG deviations in schizophrenia may recede when the illness reaches a very chronic stage , although this hypothesis is less tenable . There were significant differences between placebo and the three neuroleptics in terms of increased amplitudes in the delta and theta frequency b and s in the anterior head regions , which is compatible with data from other studies . These changes were most pronounced with clozapine and least prominent with haloperidol , with chlorpromazine occupying an intermediate position . This order happens to parallel their relative antiserotonergic , antihistaminic and anticholinergic properties . The latter may have been partially obscured by the addition of benztropine . In a subgroup of patients who were recorded under each of the treatment conditions , there were more fast frequencies with clozapine than with the other neuroleptics agreeing with Roubicek and Major . This could be a function of clozapine 's increased adrenergic activity as reported by Ackenheil . An unexpected finding was that patients who responded to clozapine had higher amplitudes in the alpha spectrum , most pronounced in the left anterior quadrant , than did the nonresponders . These differences between responders and nonresponders obtained whether patients were on placebo , haloperidol or clozapine . Curiously , Buchsbaum et al. found that anxious patients who responded to benzodiazepines also had higher alpha amplitudes in the same brain regions , which differentiated them from nonresponders . These findings clearly warrant future scientific investigation . In this regard , the generalizability of our data is limited by the extremely chronic , treatment-resistant population studied . However , promising directions for further research in EEG and psychopharmacology have been identified In a controlled study , inpatient violence was measured during placebo , high-potency ( haloperidol ) and low-potency ( chlorpromazine or clozapine ) neuroleptics . Some patients had a marked increase in violent behavior with the moderately high-dose haloperidol , but not with low-potency neuroleptics . The authors discuss reasons for the increased violence with haloperidol , including akathisia and drug-induced behavioral toxicity The purpose of this study was to investigate whether L-DOPA antagonizes chlorpromazineor haloperidol-induced parkinsonism in schizophrenic patients . The following considerations motivated our research : a ) in Parkinson ’s disease there is a decrease in the dopamine content of the corpus striaturn and the substantia nigra ( Ehringer & Hornykiewicz 1960 ; Hornykiewicz 1963 ; Barolin et al. 1964 ) ; b ) L-DOPA increases dopamine concentration in the extrapyramidal centres ( Bertler & Rosengren 1959 ) : c ) L-DOPA antagonizes reserpine-induced parkinsonism ( Degkwitz et al. 1960 ) and the extrapyramidal symptoms of Parkinson ’s disease ( Birkmayer & Hornykiewicz 1961 , 1962 , 1964 ; Barbeau et al. 1962 ; Friedhoff et al. 1963 ; Gerstenbr and et al. 1963 ) ; d ) chlorpromazine and haloperidol produce a very significant increase in dopamine and homovanillic acid ( HVA ) urinary excretion when schizophrenics , treated with large therapeutic doses , show marked extrapyramidal symptoms ( Bruno et al. 1963 ; Bruno & Allegranza 1965 ) Extrapyramidal side effects of neuroleptics are important in clinical practice . Study of extra-pyramidal side effects is also of importance for research ers who test new antipsychotic agents or study tardive dyskinesia . A french translation of the Simpson-Angus Rating Scale of extra-pyramidal side effects thus appeared useful . This scale contains 10 items : Gait , Arm dropping , Shoulder shaking . Elbow rigidity , Wrist rigidity , Leg pendulousness , Head dropping , Glabella Tap , Tremor , Salivation . Each item is rated between 0 and 4 . A total score is obtained by adding the items and dividing by 10 . Scores of up to 0.3 are considered within the normal range . The scale original has been vali date d in a population of fourteen psychotic in patients taking , in a double-blind procedure , placebo , haloperidol 6 mg/day or haloperidol 30 mg/day . Patients receiving haloperidol 30 mg/day presented more extrapyramidal symptoms than patients under placebo . The Simpson Angus rating scale has also been shown to have clinical validity and high inter-rater reliability . It can be routinely used in clinical drug evaluation . The french version was used in a population of 30 psychotic in patients fulfilling the DSM III-R criteria of schizophrenic disorder . Patients were treated for at least two weeks , orally , either with a phenothiazine ( chlorpromazine 350 mg ) or a butyrophenone ( haloperidol 15 mg ) . 10 of the 30 patients received , in addition , anticholinergic agents ( trihexiphenidyl , 5 mg ) . The french version of The Simpson Angus Rating Scale appeared to be easy to use and not time-consuming . Interraters correlation was high . Patients receiving butyrophenones or phenothiazines had no significantly different ages and sociodemographic characteristics . ( ABSTRACT TRUNCATED AT 250 WORDS Trade names of drugs mentioned in this paper : haloperidol , Haldol ( McNeil Laboratories , Fort Washington , Pa. ) ; ehlorpromazine , Thorazine ( Smith Kline and French , Philadelphia , Pa. ) ; benztropine , Cogentin ( Merck Sharp and Dohme , West Point , Pa. ) ; diphenhydramine , Benadryl ( Parke-Pavis , Detroit , Mich. ) . The effect of an anticholinergic antiparkinsonism drug , benztropine , on the therapeutic course of neuroleptie treatment in 18 schizophrenics was investigated in a double blind cross-over study involving haloperidol and ehlorpromazine . Significant therapeutic reversal was observed with benztropine in terms of the social , affective , and cognitive dysfunctions characteristically seen in schizophrenic psychosis . The hallucinatory behavior and disturbed attention were not so affected . The aspects of the clinical picture to show significant nontherapeutic change with benztropine differed with the stage of treatment and seemed to be determined by the kinetics of the therapeutic process . The effect was one of exacerbation of the disorder and not a toxic confusional state sometimes associated with anticholinergic drugs . The practical and theoretical significance of these findings was discussed . It was suggested that the benztropine reversal of therapeutic changes provided a valuable pharmacological model for underst and ing the neurobiological basis of schizophrenic decompensation and its restitution with neuroleptics . The reported data were considered as indirect evidence suggesting that cholinergic neuronal mechanisms are involved in both of these processes . It was speculated that these mechanisms may well be the cholinergic suppressor systems , such as the periventricular system , which function in reciprocal relationship with the facilitatory catecholamine pathways in the limbic organization and basal ganglia known to be affected by neuroleptics Prophylactic effects of psychotropic drugs on 55 schizophrenics in remission were evaluated for 3 years in a double-blind controlled study employing a cross-over design . Patients were r and omly assigned to the following drugs orally administered twice a day : placebo ; diazepam 15 mg ; imipramine 50 mg ; chlorpromazine 75 mg ; and haloperidol 3 mg . The number of days of remission for each patient was recorded . Since only two patients received all five drug treatments , the data were analyzed using the number of days allocated to the “ first assigned drugs ” only and the cross-over aspect of the experimental design was disregarded . All patients treated with either the placebo , diazepam or imipramine relapsed within a year . On the other h and , four patients treated with chlorpromazine , or with haloperidol , were in remission for more than 1 year . Fifty percent of the patients relapsed within 16 days with placebo ; 88 days with diazepam ; 30 days with imipramine ; 165 days with chlorpromazine ; and 74 days with haloperidol . Within a year , only chlorpromazine significantly prolonged the remission state as compared to placebo and imipramine . At the end of the 3-year trial , both chlorpromazine and haloperidol significantly prolonged the remission state as compared to the other three drugs . These data suggest that neuroleptic treatment for a longer period is vitally important to prevent relapse even in schizophrenics in remission and that such a trial seems an efficient method for investigating the prophylactic effects of neuroleptics A pilot study of a small group of schizophrenic patients manifesting symptoms of a depressive nature was treated in a double-blind study in which viloxazine or a placebo was administered in combination with either chlorpromazine or haloperidol . There appeared to be no difference between the viloxazine-treated group and the placebo-treated group , although the study raised some question as to the adequacies of the dosage utilized since there was an absence of any apparent side effects . In view of these issues concerning the clinical merit of the combination , this obviously requires further investigation In a double blind chlorpromazine-controlled trial , high dosage haloperidol ( 100 mg daily ) given for three months , appreciably improved the mental state of male chronic ' drug resistant ' schizophrenic in patients in the rehabilitation/long-stay unit of one psychiatric hospital . The results of a three-month follow-up suggested that the improvement could be maintained in some patients on lower doses of the drug . Serious extrapyramidal side effects were not seen at high doses . However , the majority of patients on haloperidol showed a deterioration in ward behaviour , possibly related to drowsiness , and developed raised serum alkaline phosphatase levels . These side effects disappeared in the follow-up period when either the drug was discontinued or the dose of haloperidol reduced In this research we investigated the effects of 4 antipsychotic drugs with different anticholinergic components on different memory functions of schizophrenic patients . Drugs were administrated in cumulative doses and memory was tested 90 min after each drug was administered . The results show that chlorpromazine and thioridazine impaired short‐term verbal memory after 6 h of sequential administration . Trifluoperazine and haloperidol improved short‐term verbal memory from the third to the fifth administration . Immediate memory , long‐term memory and visual short‐term memory were not impaired by any drug Cholinergic blocking with scopolamine produces skin conductance orientating response ( SCOR ) nonresponding in normal subjects . This may be one of a number of causes for nonresponding in schizophrenic subjects . Blockade of dopamine with haloperidol produces an increase in amplitude and shortening of recovery time in the SCOR of normal subjects . This result closely resembles that of Nielsen and Petersen ( 1976 ) who found a similar pattern of responding in normal subjects who scored high on a scale of schizophrenism . These results , along with those for chlorpromazine and the pupillographic effects of the three drugs are discussed in terms of biochemical working hypotheses of schizophrenic subclassification The treatment process with two prototypic neuroleptics — haloperidol and chlorpromazine— and the nontherapeutic effects of trihexyphenidyl on this process were studied in carefully matched groups of ten schizophrenics each , using a “ double-blind ” , repeated-measure , longitudinal research design . Measurements of various aspects of psychopathology , social participation and clinical indices of arousal were made periodically and objective tests of cognition and attention were given . The two treatment groups were highly comparable in epidemiological and clinical terms and differed significantly during the baseline period in only one of the 39 parameters . Longitudinal nonparametric analyses showed that significant therapeutic changes tended to occur more quickly and involved a wider spectrum of schizophrenic phenomena with haloperidol than with chlorpromazine . Parametric analyses also indicated that at the completion of the study , haloperidol-treated patients had significant improvement in many more dimensions than the chlorpromazine-treated patients and that the changes with haloperidol were generally of greater magnitude . At the same time , chlorpromazine treatment seemed to be more susceptible to the antagonistic effects of trihexyphenidyl . No differential patterns of responses were noted for the two neuroleptics to provide any clinical validity to the distinction often made between “ sedative ” and “ activating ” neuroleptics . These data were in agreement with those from a previous comparative study which had a very different research design and a somewhat different type of schizophrenic population . The clinical and potency differences between the two neuroleptics were again explained on the basis of the fact that chlorpromazine has much stronger built-in anticholinergic properties , which may be acting in opposition to the antipsychotic activity . It was suggested that the degree of inherent anticholinergic activity may be an important determinant of potency differences among presently known neuroleptics . The possible role of cholinergic mechanisms in schizophrenia was discussed The occipital EEG , integrated by a modulus voltage integrator to yield measurements of i ) mean amplitude over time , ii ) the coefficient of variation of integrated amplitude from moment to moment has been found less variable in signal content in chronic schizophrenics in several replicated studies ( 1 , 4 ) . Those acute schizophrenics who hallucinated during the recording also had relatively invariable EEG 's as compared to other acute schizophrenics or non-psychotic control subjects , although acute schizophrenics in general did not differ from the normals ( 4 ) . Mean integrated amplitude scores did not differ significantly between any of the groups , did not discriminate those patients hallucinating and showed no sex difference in our studies . In hospitalized chronic schizophrenic patients the measure has been shown to be sensitive to clinical symptomatic change induced by antipsychotic agents of a wide variety ( 6 ) , although correlations at one point in time did not relate the integrator scores to clinical symptomatic status across a patient sample . In our acute schizophrenic sample s the five unmedicated patients had a higher mean coefficient of variation than the 55 receiving drugs ( 4 ) : this posed the question of comparability of the acute schizophrenics , mostly medicated , with the unmedicated non-psychotic volunteers In order to evaluate the influence of some neuroleptics on unproductive symptoms of schizophrenic process , first hospitalized patients with paranoid schizophrenia underwent monotherapy with perazine , fluphenazine , trifluoroperazine , chlorpromazine , and haloperidol . All the drugs eliminated the productive activity of the disease process within 2 months in both women and men aged 18 - 40 years . However , drugs showed different qualitative and quantitative effects on unproductive symptoms of schizophrenic process ; this fact allows the suggestion regarding the particular usefulness of drugs in the out-patient care In a double-blind placebo controlled clinical trial in chronic schizophrenic patients , haloperidol and clopenthixol were found to be effective antipsychotic agents , favorably altering behavior as observed by the psychiatrist , the nurse , and ward attendants . In this respect they appeared to compare adequately to the st and ard drug , chlorpromazine . In this experiment , neither the st and ard drug nor the investigational drugs affected psychological test performance . The expected side effects such as extrapyramidal signs and sedation did occur and in some instances required dose reduction for alleviation . One case of possible hepatoxicity in the CX group occurred at the end of the study and was considered of serious import requiring cessation of medication . It was concluded that these chemically unrelated antipsychotics could be used in practice as therapeutic alternatives , the particular choice depending on side effects and possibly symptomatology It is possible that the most powerful “ drug ” in childhood management is the emotionally warm , reality orientated and consistently predictable parent . Such a concept can be exitended to the doctor or any other professional worker who is perceived to have similar qualities by his patients ( Balint 1961 ) . Against this , when psychoactive drugs are prescribed for children , one has to evaluate their varying pharmacological effects . This includes placebo and side effects which themselves may have a dynamic interaction and facilitate or retard behavioural changes in the child and attitudes in the parent . Generally child psychiatrists are reluctant to exhibit drugs in the first instance as all too frequently by the time a child is referred there is a history of multiple drug failure . It is believed that for this reason drugs may be underor over-valued and that the indications for their use are not yet well established . Yet it is the clinical experience of most professional workers in this field that drugs exert both powerful and specific effects and should be included in the therpeutic armamentarium . This study attempts to assess the symptoms , traits and behaviour of a sample of disturbed children over a specified period during which they were given a sequence of psychoactive drugs , a placebo and a no-drug period . An attempt was made at the same time to assess the observable dynamics of the parent-child interaction and the probable relationship this has to the effects of psychoactive drugs BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials |
13,519 | 20,556,761 | Creatine was reportedly well-tolerated in all three included studies , with no evidence of renal failure or serious adverse events specifically attributable to creatine .
In patients already diagnosed with clinical ly probable or definite amyotrophic lateral sclerosis ( ALS ) , creatine at doses ranging from 5 to 10 g per day did not have a statistically significant effect on survival , ALS functional rating revised scores ( ALSFRS-R ) progression or percent predicted forced vital capacity ( FVC ) progression | BACKGROUND Creatine , a naturally-occurring nitrogenous organic acid involved in adenosine triphosphate ( ATP ) production , has been shown to increase survival in mouse models of amyotrophic lateral sclerosis ( ALS ) .
Results from human trials , however , have been mixed .
Given conflicting results regarding creatine 's efficacy , we conducted a systematic review .
OBJECTIVES To systematic ally examine creatine 's efficacy in prolonging ALS survival and in slowing ALS disease progression . | The topiramate study was a 12-month r and omized placebo-controlled trial in patients with ALS . Follow-up evaluation of the placebo group ( n = 97 ) constituted a well-described cohort of patients with ALS , in whom multiple outcome measures were assessed at 3-month intervals . During the 12-month study period , the decline of forced vital capacity ( FVC% ) and ALS functional rating scale ( ALSFRS ) was linear , whereas the decline of maximum voluntary isometric contraction – arm ( MVIC-arm ) and MVIC-grip Z scores was curvilinear . Rates of FVC% and ALFRS decline , but not of MVIC-arm or MVIC-grip , were independent predictors of survival Our objective was to determine the effect of creatine monohydrate on disease progression in patients with amyotrophic lateral sclerosis ( ALS ) . One hundred and seven patients with the diagnosis of probable or definite ALS , of less than five years duration from symptom onset , were r and omized to either treatment with daily creatine monohydrate ( 5 g/d ) or placebo . In this multicenter , double-blinded study we followed changes in disease progression : using quantitative measures of strength via maximal isometric voluntary contraction , forced vital capacity , ALSFRS , quality of life , fatigue and survival . Patients were followed for nine months . The results showed that creatine monohydrate did not significantly improve motor , respiratory or functional capacity in this patient population . The drug was well tolerated and the study groups well balanced , especially considering the absence of forced vital capacity criteria for entrance into the study . There was a trend toward improved survival in patients taking daily creatine monohydrate and this was identical to the trend seen in another recently published report of creatine in ALS patients 1 . In conclusion , creatine monohydrate ( 5 g/d ) did not have an obvious benefit on the multiple markers of disease progression measured over nine months . We measured fatigue during isometric contraction and found no significant improvement despite anecdotal patient reports prior to and during the study . The trend toward improved survival was also found in another recently completed blinded trial using creatine monohydrate . Further investigation on the possible survival benefit of creatine in this patient population is ongoing The ALS Functional Rating Scale ( ALSFRS ) is a vali date d rating instrument for monitoring the progression of disability in patients with amyotrophic lateral sclerosis ( ALS ) . One weakness of the ALSFRS as originally design ed was that it granted disproportionate weighting to limb and bulbar , as compared to respiratory , dysfunction . We have now vali date d a revised version of the ALSFRS , which incorporates additional assessment s of dyspnea , orthopnea , and the need for ventilatory support . The Revised ALSFRS ( ALSFRS-R ) retains the properties of the original scale and shows strong internal consistency and construct validity . ALSFRS-R scores correlate significantly with quality of life as measured by the Sickness Impact Profile , indicating that the quality of function is a strong determinant of quality of life in ALS The Scottish Motor Neuron Disease Register ( SMNDR ) is a prospect i ve , collaborative , population -based project which has been collecting data on incident patients since 1989 . In this report we present the clinical features of 229 patients with motor neuron disease ( 218 sporadic and 11 familial ) diagnosed in 1989 and 1990 and compare their prognosis with previous studies of survival . The overall 50 % survival from symptom onset was 2.5 years ( 95 % CI , 2.2–3.0 ) and 5-year survival 28 % ( 95 % Cl , 20–36 % ) . The presence of progressive bulbar palsy ( PBP ) , either at presentation or developing during the course of the illness , significantly reduced survival and was the most important prognostic indicator . Patients who survived longer than 5 years from symptom onset did not have BP as part of their presenting illness . The prognosis was worse for women , and this was in part related to the higher frequency of PBP in older women , but age was also an independent adverse risk factor . Differences in survival between this and previous series can probably be explained on the basis of variation in case definition and ascertainment methods Background : In recent years , there has been a paradigm shift in the method of healthcare delivery to amyotrophic lateral sclerosis ( ALS ) patients with the emergence of multidisciplinary ALS clinics that cater exclusively for patients with this condition . The impact of multidisciplinary management has not been previously evaluated . Methods : Using data from the Irish ALS Register , we conducted a prospect i ve , population based study of all ALS cases diagnosed in Irel and over a five year period to evaluate the effectiveness of a multidisciplinary clinic on ALS survival . Results : Eighty two ( 24 % ) patients attended the multidisciplinary ALS clinic , with the remaining 262 ( 76 % ) cases followed in a general neurology clinic . The ALS clinic cohort was an average of five years younger ( 60.1 v 65.6 years ) and were more likely to receive riluzole than the general neurology cohort ( 99 % v 61 % ) . The median survival of the ALS clinic cohort was 7.5 months longer than for patients in the general neurology cohort ( logrank = 15.4 , p < 0.0001 ) . Overall , one year mortality was decreased by 29.7 % . Prognosis of bulbar onset patients was extended by 9.6 months if they attended the ALS clinic . Using multivariate analysis , attendance at the ALS clinic was an independent covariate of survival ( HR = 1.47 , p = 0.02 ) . Conclusions : ALS patients who received their care at a multidisciplinary clinic had a better prognosis than patients attending a general neurology clinic . The data suggest that active and aggressive management enhances survival , particularly among ALS patients with bulbar dysfunction . The effect of clinic type must be considered in future clinical trials design Objective : To determine the incidence , prevalence , and mortality rates of ALS in the province of Modena , Northern Italy , from 1990 through 1999 . Methods : A retrospective epidemiologic study was conducted , ascertaining cases from all neurologic centers and hospitals of the province , death certificates , and the Italian ALS Association , section of Modena . All clinical records were review ed , and only patients fulfilling the El Escorial revised diagnostic criteria were included . Results : During the period considered ( 1990 to 1999 ) , 143 residents ( 67 men and 76 women ) entered the study . The average annual incidence was 2.16 per 100,000 , with a peak in the age class of 75 to 79 years . Mean prevalence rate was 4.02 per 100,000 , and mean mortality rate was 1.69 per 100,000 . The incidence rate remained constant over time , whereas the prevalence and mortality rates increased owing to a rise in survival time ( ALS mean duration was 17.38 months in 1990 , 43.18 months in 1999 ) . In the mountainous areas , where agricultural work is more common , the incidence , prevalence , and mortality rates were higher than in urban areas and the disease onset occurred 10 years later . Of the risk factors examined , only agricultural work and rural residence were significant . Conclusions : The incidence , prevalence , and mortality rates agree with those in recent Italian surveys and with most international studies , but the distribution of cases varied with higher rates in mountainous areas . Further prospect i ve studies are required ALS is a progressive motor neuron disease with no effective treatment . The anti-excitotoxic drug riluzole ( 100 mg/day ) has been shown to decrease mortality and muscular deterioration in ALS patients . To confirm and extend the therapeutic effect of riluzole , we performed a double-blind , placebo-controlled , multicenter , international , dose-ranging ( 50 , 100 , 200 mg/day ) , stratified study in 959 ALS out patients treated for up to 18 months . Primary efficacy criterion was survival and the effect of treatment was analyzed before ( Wilcoxon and log rank tests ) and after adjustment on prognostic factors ( Cox model ) . Secondary efficacy criterion was disease progression assessed through change in functional measures . Tracheostomy-free survival rates were : 50.4 % ( placebo ) , 55.3 % ( 50 mg riluzole ) ( p = 0.23 , Wilcoxon test ; p = 0.25 , log-rank test ) , 56.8 % ( 100 mg riluzole ) ( p = 0.05 , Wilcoxon test ; p = 0.076 , log-rank test ) , and 57.8 % ( 200 mg riluzole ) ( p = 0.061 , Wilcoxon test ; p = 0.075 , log-rank test ) . At the end of the 18-month study , there was a significant dose-related decrease in risk of death or tracheostomy ( p = 0.04 ) . Adjustment for baseline prognostic factors showed a 35 % decreased risk of death with the 100-mg dose compared with placebo ( p = 0.002 ) . No significant treatment effects were detected for the functional assessment s. The most frequent dose-related adverse events included nausea , asthenia , and elevated liver enzyme levels . This study confirms the therapeutic effect of riluzole in a large representative ALS sample , over an 18-month period . Riluzole is well tolerated and decreases the risk of death or tracheostomy in ALS patients . NEUROLOGY 1996;47(Suppl 4 ) : Creatine supplementation in humans has been reported to enhance power and strength both in normal subjects and in patients with various neuromuscular diseases . The purpose of this study was to examine the effects of supplementation on exercise performance and maximal voluntary isometric muscular contraction ( MVIC ) in Amyotrophic Lateral Sclerosis ( ALS ) patients . We report the results obtained in 28 patients with probable/definite ALS . In each patient we acquired the dynamometric measurement of MVIC in 10 muscle groups of upper and lower limbs and a measure of fatigue by means of an high-intensity intermittent protocol in elbow flexors and knee extensors muscles . All patients completed the protocol s at the baseline and after supplementation of 20 g per day for 7 days and after supplementation of 3 g per day for 3 and 6 months . MVIC increased after 7 days of supplementation in 20 patients ( 70 % ) in knee extensors and in 15 ( 53 % ) of them also in elbow flexors . A statistically significant difference between pre and post-treatment mean values of MVIC was found both in elbow flexors ( P<0.05 ) and knee extensors ( p<0.04 ) . The analysis of the slopes of fatigue test showed a statistically significant improvement after 7 days of supplementation in 11 patients ( 39 % ) in elbow flexors and in 9 patients ( 32 % ) also in knee extensors muscles . During the 6-month follow-up period all the examined parameters showed a linear progressive decline . In conclusion , our preliminary results have demonstrated that supplementation temporary increases maximal isometric power in ALS patients so it may be of potential benefit in situations such as high intensity activity and it can be proposed as a symptomatic treatment Amyotrophic lateral sclerosis ( ALS ) is a fatal disease with no cure . In a transgenic mouse model of ALS , creatine monohydrate showed a promising increase in survival . We performed a double‐blind , placebo‐controlled , sequential clinical trial to assess the effect of creatine monohydrate on survival and disease progression in patients with ALS . Between June 2000 and December 2001 , 175 patients with probable , probable‐laboratory supported , or definite ALS were r and omly assigned to receive either creatine monohydrate or placebo 10gm daily . A sequential trial design was used with death , persistent assisted ventilation , or tracheostomy as primary end points . Secondary outcome measurements were rate of decline of isometric arm muscle strength , forced vital capacity , functional status , and quality of life . The trial was stopped when the null hypothesis of indifference was accepted . Creatine did not affect survival ( cumulative survival probability of 0.70 in the creatine group vs 0.68 in the placebo group at 12 months , and 0.52 in the creatine group vs 0.47 in the placebo group at 16 months ) , or the rate of decline of functional measurements . Creatine intake did not cause important adverse reactions . This placebo‐controlled trial did not find evidence of a beneficial effect of creatine monohydrate on survival or disease progression in patients with ALS . Ann Neurol Amyotrophic lateral sclerosis is a rapidly progressive disease of unknown etiology result ing in tetraparalysis , dysarthria , dysphagia , and ultimately death from respiratory insufficiency . In the course of the disease , recurrent episodes of aspiration , pneumonia , dehydration , and malnutrition may necessitate nasoenteral tube placement , an inconvenient and unattractive arrangement in patients with dribbling and impaired swallowing . A percutaneous endoscopic gastrostomy seemed a better , though potentially hazardous , alternative in view of the often severely restricted pulmonary function of these patients . Therefore , we prospect ively investigated the use of percutaneous endoscopic gastrostomy in 68 consecutive patients with amyotrophic lateral sclerosis . Minimum required pulmonary function was defined as forced vital capacity ( FVC ) of 1 L or more and CO2 gas exchange capability as pCO2 of 45 mm Hg or less . The methodology of insertion was adapted to facilitate the early removal of gastric air . Fifty-five patients ( median FVC , 1.7 L ; pCO2 , 40 mm Hg ) were eligible for the gastrostomy procedure , and 13 patients ( median FVC , 0.8 L ; pCO2 , 47 mm Hg ) were not . Despite the fact that modification of the method of insertion rendered the procedure more difficult , the success rate was 89 % ( 49/55 ) ; it was 96 % ( 49/51 ) when failures related to distorted anatomy were excluded . The procedure-related mortality rate was 1.8 % and the 24-hour in-hospital mortality rate was 3.6 % , mainly related to respiratory insufficiency . The 30-day out-of-hospital mortality rate was 11.5 % . Major complications ( 3.6 % ) consisted of a spontaneously draining cutaneous abscess in 2 cases . Peristomal redness was present in 6 cases , and 5 patients required analgesics for wound pain . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE : To evaluate the effect of creatine supplementation on the respiratory function of patients with advanced amyotrophic lateral sclerosis ( ALS ) . METHODS : Five grams creatine daily were administered orally to 14 patients with definite advanced ALS . For comparison we used a group of 13 patients with a similar respiratory function . All patients performed pulmonary function testing including forced vital capacity ( FVC ) , forced expiratory volume ( FEV 1 ) , peak expiratory flow rate ( PEF ) and maximum voluntary ventilation ( MVV ) - expressed as percent of the predicted value - at baseline and each month thereafter . RESULTS : There was no significant difference in any measured variable between the treatment group and the control group at 1 , 2 , 3 and 4 months follow-up . Thereafter the high patient drop-out rate did not allow statistical evaluation . CONCLUSION : The present study did not show any clinical ly significant , long-term effect of creatine on the function of respiratory muscles in ALS patients with respiratory distress Background : Mitochondrial dysfunction occurs early in the course of ALS , and the mitochondria may be an important site for therapeutic intervention . Creatine stabilizes the mitochondrial transition pore , and is important in mitochondrial ATP production . In a transgenic mouse model of ALS , administration of creatine prolongs survival and preserves motor function and motor neurons . Methods : The authors conducted a r and omized double-blind , placebo controlled trial on 104 patients with ALS from 14 sites to evaluate the efficacy of creatine supplementation in ALS . The primary outcome measure was maximum voluntary isometric contraction of eight upper extremity muscles , with secondary outcomes including grip strength , ALS Functional Rating Scale – Revised , and motor unit number estimates . Patients were treated for 6 months , and evaluated monthly . Results : Creatine was tolerated well , but no benefit of creatine could be demonstrated in any outcome measure . CI analysis showed that the study , although powered to detect a 50 % or greater change in rate of decline of muscle strength , actually made an effect size of greater than 23 % unlikely . It was also demonstrated that motor unit number estimation was performed with acceptable reproducibility and tolerability , and may be a useful outcome measure in future clinical trials . Conclusion : Any beneficial effect of creatine at 5 g per day in ALS must be small . Other agents should be considered in future studies of therapeutic agents to address mitochondrial dysfunction in ALS . In addition , motor unit number estimation may be a useful outcome measure for future clinical trials in ALS BACKGROUND Amyotrophic lateral sclerosis is a progressive motor neuron disease for which there is no adequate treatment . Some research suggests that the excitatory amino acid neurotransmitter glutamate may be involved in the pathogenesis . METHODS To evaluate the efficacy and safety of the antiglutamate agent riluzole , we conducted a prospect i ve , double-blind , placebo-controlled trial in 155 out patients with amyotrophic lateral sclerosis . The dose of riluzole was 100 mg per day . R and omization was stratified according to the site of disease onset ( the bulbar region or the limbs ) . The primary end points were survival and rates of change in functional status . The main secondary end point was change in muscle strength . Analyses were undertaken after 12 months of treatment and at the end of the placebo-controlled period ( median follow-up , 573 days ) . RESULTS After 12 months , 45 of 78 patients ( 58 percent ) in the placebo group were still alive , as compared with 57 of 77 patients ( 74 percent ) in the riluzole group ( P = 0.014 ) . For patients with bulbar-onset disease , one-year survival rates were 35 percent ( 6 of 17 ) with placebo and 73 percent ( 11 of 15 ) with riluzole ( P = 0.014 ) , whereas for those with limb-onset disease one-year survival was 64 percent and 74 percent , respectively ( P = 0.17 ) . The survival advantage with riluzole was smaller ( 37 percent [ 29 of 78 ] with placebo vs. 49 percent [ 38 of 77 ] with riluzole ) at the end of the placebo-controlled period , but it remained significant in the overall population ( P = 0.046 ) as well as in the patients with bulbar-onset disease ( 18 percent [ 3 of 17 ] vs. 53 percent [ 8 of 15 ] , P = 0.013 ) . The deterioration of muscle strength was significantly slower in the riluzole group than in the placebo group ( P = 0.028 ) . Adverse reactions to riluzole included asthenia , spasticity , and mild elevations in aminotransferase levels . Twenty-seven patients in the riluzole group withdrew from the study , as compared with 17 in the placebo group . CONCLUSIONS The antiglutamate agent riluzole appears to slow the progression of amyotrophic lateral sclerosis , and it may improve survival in patients with disease of bulbar onset |
13,520 | 28,266,135 | Overall HRQL was significantly reduced on treatment .
Despite HRQL improvements over time , longitudinal studies reported a proportion of children continued to experience reduced HRQL after treatment completion .
We found inconsistent associations between clinical /demographic factors and HRQL outcomes .
Tentative evidence emerged for worse HRQL being associated with intensive phases of chemotherapy , corticosteroid therapy , experiencing greater toxicity , older age , and female sex . | Children with acute lymphoblastic leukemia ( ALL ) undergo intense anticancer treatment . | Abstract Background : Patients receiving chemotherapy for cancer often develop anemia , which can contribute to increased morbidity and reduced quality of life ( QOL ) . Chemotherapy-induced anemia can be successfully treated using recombinant human erythropoietin ( rHuEPO ) . Aim of the study : To demonstrate the effectiveness of once-weekly ( QW ) rHuEPO dosing to effect improved hemoglobin levels , decreased transfusion use , and improved functional outcomes and QOL in pediatric leukemic patients ( ALL ) receiving maintenance chemotherapy . Patient and methods : This was a prospect i ve r and omized , single-center , open-label , 12-week case-control study of epoetin alfa in pediatric patients with acute lymphoblastic leukemia ( ALL ) in remission receiving maintenance chemotherapy . Sixty patients were r and omly assigned to receive either epoetin alfa ( rHuEPO group = 30 cases , 17 males and 13 females , age ; 6.8 ± 2.33 years ) , or no epoetin alfa ( control group = 30 cases , 16 males and 14 females , age ; 6.76 ± 2.28 years ) . Both groups were matched as regard age , sex , baseline Hb concentration , remission state , chemotherapy regimen , numbers and amount of blood transfusion , and leukemia state ( both were low and st and ard risk ) . Epoetin alfa was administered at a dose of 450 IU/kg , once weekly , subcutaneously ( s.c . ) for 12 consecutive weeks . Endpoints were changes in hematologic and QOL parameters . Results : Among the 30 patients evaluable for hematologic response , the mean increase in Hb from baseline to time of final evaluation was 3.08 ± 1.48 g/dl ( p < 0.001 ) . An increase in Hb of ≧ 2 g/dl , in the absence of blood transfusion , occurred in 70 % of patients ( 21 of 30 patients ) who were on the study for ≧ 30 days . The overall response rate ( Hb increase ≧ 2 g/dl or Hb ≧ 12 g/dl in the absence of blood transfusion ) was 90 % ( 27 of 30 patients ) . In 30 patients who were evaluable for QOL assessment , epoetin-α therapy was found to significantly ( p < 0.001 ) improve mean cancer linear analog scale ( CLAS ) scores for energy level , ability to perform daily activity , and overall QOL from baseline to the time of final evaluation . QW epoetin-α was found to be well tolerated . Conclusion : Treatment with QW epoetin-α was found to increase Hb levels , decrease transfusion requirement , and improve functional status and QOL in anemic patients with ALL in maintenance receiving chemotherapy . The once-weekly schedule is convenient , safe , and may reduce the burden on patients , parents , and their caregivers by reducing the number of visits to the clinic Using a multi-attribute approach , we and others have reported on the comprehensive health status of survivors of cancer in childhood , after completion of therapy . However , there is a dearth of information about health status and associated health-related quality of life ( HRQL ) in children and adults with cancer , during the treatment process ; a deficit which this study was intended to redress . All children ( n=18 ) receiving ' maintenance ' chemotherapy for acute lymphoblastic leukemia ( ALL ) at a single institution were assessed prospect ively through a single cycle of therapy . Patients , family members and health care professionals used global ratings , the health utilities index mark 2 ( HUI2 ) and mark 3 ( HUI3 ) classification systems , and detailed descriptions of temporary states of health , to provide independent assessment s of health status at weekly intervals . Utility scores were derived for each comprehensive health state and for single attribute levels of the HUI2 system , and for the temporary health state descriptions . The classification of the subjects into the most appropriate temporary health states was challenging even for older children and some of the parents . The HUI instruments were used much more easily and produced highly comparable information . The most frequently affected attributes were pain , emotion and mobility/ambulation ; in that order . The global ( p=0.005 ) and specific morbidity burdens were , as predicted , greatest in the middle of the cycle of chemotherapy , reflecting the toxicity of steroid use . HUI2 global utility scores demonstrated moderate responsiveness with an intra-class correlation coefficient of 0.43 . Cyclical administration of therapy , in particular corticosteroids , produces important changes in health status and HRQL in children with ALL . The HUI are valid and responsive systems for quantifying the burden of morbidity during the treatment of cancer in childhood . These are sensitive tools which can be used in a wide array of other circumstances to quantify changes in health status Background Glucocorticoids are important in the treatment of childhood acute lymphoblastic leukaemia ( ALL ) . However , cyclic administration of high dose glucocorticoids may cause rapid and substantial changes in quality of life ( QoL ) . The maintenance phase of the Dutch ALL-9 protocol consisted of alternating two weeks on and five weeks off dexamethasone ( 6 mg/m2/day ) . The present study was performed to assess the effect of dexamethasone on QoL during treatment for ALL according to this protocol . Methods In a multicentre prospect i ve cohort study , QoL was assessed halfway ( T1 ) and at the end of the two-year treatment ( T2 ) . A generic ( Child Health Question naire ) and disease specific ( PedsQL ™ cancer version ) QoL question naire were used to assess QoL in two periods : on and off dexamethasone , respectively . Results 41 children ( 56 % males ) were evaluated , mean age at diagnosis was 5.6 years . The CHQ physical and psychosocial summary scores were significantly lower than population norms . At T1 and T2 , overall QoL showed no significant change . However , regarding specific domains ( pain , cognitive functioning , emotion/behaviour and physical functioning ) QoL decreased over time . QoL was significantly more impaired during periods on dexamethasone . Conclusion Dexamethasone was associated with decreased QoL. At the end of treatment , reported QoL during dexamethasone deteriorated even more on certain scales ( pain , cognitive functioning , emotion/behaviour and physical functioning ) . Knowledge of the specific aspects of QoL is essential to improve counselling and coping in paediatric oncology . Adverse effects of specific drugs on QoL should be taken into account when design ing treatment protocol Background The quality of life of children with leukemia is reduced by fear and anxiety of parents after diagnosis , lack of information about the disease , treatments , and care of the child . This study aims to evaluate the effect of educating parents of leukemic children on the patients ’ quality of life . Methods In this interventional study , sixty parents of ALL children who met inclusion criteria were selected using simple r and om sampling method , and assigned to the experimental and control groups . The study tool included a valid and reliable question naire ( TNO-AZL ) , that was filled in through interview by parents before and two months after the intervention for both groups . The first part of the question naire included demographic items and the second part ( 7 dimensions , each with 8 sections ) contained questions related to the quality of life . The scores could range between 56 and 280 and a higher score represented a better quality of life . The intervention included three one-hour classes composed of lecture and question -answer sessions which were held for groups of 4 - 6 participants , accompanied by a booklet . Results Before the intervention , the quality of life score in the experimental and control groups was 180.83±14.43 and 174.28±20.72 , respectively ; after the intervention , these figures changed to 226.9±11.76 and 174.41±20.42 respectively . Paired sample s T-test proved a significant increase in the quality of life in the experimental group . Conclusion Parent education successfully increased the quality of life of leukemic children ; therefore , parental consultation sessions and educational programs are recommended BACKGROUND This study investigates the effect of using patient reported outcomes ( PROs ) about health-related quality of life ( HRQOL ) in clinical practice on the type and amount of psychosocial topics discussed during a paediatric oncology consultation . PROCEDURE Children ( N = 193 ) with cancer participated in a sequential cohort intervention study , with a control ( no PRO was used ) and intervention group ( a PRO was used ) . For each child three consecutive consultations with the paediatric oncologist were audio recorded in order to assess the discussed psychosocial topics . One third of the audio recordings were qualitatively analysed . RESULTS The type of the discussed psychosocial topics in the control and intervention group did not differ from each other . However , the discussion of psychosocial topics increased in the intervention group compared to the control group . In both groups , topics within the social domain occurred most frequently and topics regarding the emotional domain had the lowest incidence . CONCLUSIONS PROs do not change the psychosocial content of communication . Paediatric oncologists already address psychosocial issues during the consultation , regardless of the use of a PRO . However , with a PRO available they address these issues more systematic ally and more often Background Most studies on health-related quality of life ( HRQOL ) in children with cancer focussed on survivors . Only few studies have evaluated patients during ongoing oncological treatment . The aim of this study was a prospect i ve assessment of HRQOL in children during the first year after diagnosis of cancer and an examination of demographic , medical , and parental predictors of HRQOL . Methods Fifty-two patients ( mean age : 10.9 years ) were assessed 6 weeks and 1 year after diagnosis with the TNO-AZL Question naire for Children 's Health-Related Quality of Life . Parents completed the Brief Symptom Inventory . Results Compared to a community sample , patients reported more physical complaints , reduced motor functioning and autonomy , and impaired positive emotional functioning 6 weeks after diagnosis . HRQOL significantly improved over the year . However , at 1 year , patients still showed reduced motor and emotional functioning . At 6 weeks , children with leukemia were most affected . At 1 year , patients with brain tumors complained about more physical symptoms than the other groups . Intensity of treatment and presence of medical complications mainly influenced HRQOL at 6 weeks but less at 1 year . Parental psychopathology was associated with better cognitive functioning in the child . Conclusion This prospect i ve study found several domains of HRQOL to be compromised 6 weeks and 1 year after the diagnosis of cancer . Although HRQOL significantly increased over the year , there were important differences between diagnostic groups . The findings highlight the importance of repeated evaluation of HRQOL in children undergoing cancer treatment and consideration of specific differences between diagnostic groups The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)±high-dose methotrexate ( HD MTX ) in children with acute lymphoblastic leukemia ( ALL ) . 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999 . Lower-risk group ( LR , n=182 ) were r and omized to weekly low-dose MTX at 25 mg/m2/week ( LD MTX , n=81 ) or HD MTX at 1.5 g/m2/2 weeks × 6 ( n=77 ) . Intermediate-risk group ( IR , n=672 ) were r and omized to LD MTX ( n=290 ) or HD MTX at 8 g/m2/2 weeks × 4 ( n=316 ) . Higher-risk group ( HR , n=541 ) prednisone-responder patients received LD MTX and cranial radiotherapy . HR group steroid resistant cases were grafted ( autologous or allogenic ) . TIT ( MTX , cytarabine and methylprednisolone ) was given every 2 weeks during 16–18 weeks and every 3 months during maintenance therapy in LR and IR patients . 52 patients ( 3.7 % ) developed neurotoxicity . Isolated seizures : n=15 ( 1.1 % ) , peripheral and spinal neuropathy : n=17 ( 1.2 % ) and encephalopathy : n=20 ( 1.4 % ) . Age > 10 years was significantly associated with neurotoxicity ( P=0.01 ) and use of HD MTX is associated with encephalopathy ( P=0.03 ) . Sequels are reported respectively in 60 and 33 % of spinal neuropathy and encephalopathy cases . Current strategies tailoring risk of neurological sequels has to be defined St and ard risk acute lymphoblastic leukemia ( SR-ALL ) has high cure rates , but requires 2 - 3 years of therapy . We aim ed to ( i ) prospect ively evaluate health-related quality of life ( HRQOL ) during and after SR-ALL therapy , and ( ii ) identify associated predictors . Parents of 160 SR-ALL patients enrolled on Children 's Oncology Group ( COG ) therapeutic trial AALL0331 at 31 sites completed the Pediatric Quality of Life Inventory ( PedsQL ) 4.0 Generic Core Scales ( physical , emotional and social functioning ) and Family Assessment Device-General Functioning ( FAD-GF ) at 1 , 6 and 12 months after diagnosis , and 3 months post-therapy . Mean PedsQL scores in physical , emotional and social functioning were impaired 1 month after diagnosis but steadily improved . Three months post-therapy , impaired physical and social functioning was observed in 27.8 and 25.8 % of patients , respectively . In repeated- measures analysis , problematic family functioning predicted emotional ( OR = 1.85 , 95 % CI 1.03 - 3.34 ) and social ( OR = 1.99 , 95 % CI 1.21 - 3.27 ) impairment . Larger household size was associated with social impairment ( OR = 1.21 , 95 % CI 1.02 - 1.45 ) . Adverse neurological event(s ) during therapy predicted post-therapy physical ( OR = 5.17 , 95 % CI 1.61 - 16.63 ) and social ( OR = 8.17 , 95 % CI 1.19 - 56.16 ) impairment . HRQOL 1 month after diagnosis was not predictive of HRQOL 3 months after therapy completion . In conclusion , children with SR-ALL experience considerable impairment in HRQOL at the end of induction , but rapidly improve . However , many still experience physical and social impairment 3 months post-therapy , suggesting a role for continued family and physical functioning support . Longer follow-up is needed to determine if post-therapy deficits change over time PURPOSE Methotrexate ( MTX ) can cause significant clinical neurotoxicity and asymptomatic leukoencephalopathy . We sought to identify clinical , pharmacokinetic , and genetic risk factors for these MTX-related toxicities during childhood acute lymphoblastic leukemia ( ALL ) therapy and provide data on safety of intrathecal and high-dose MTX rechallenge in patients with neurotoxicity . PATIENTS AND METHODS Prospect i ve brain magnetic resonance imaging was performed at four time points for 369 children with ALL treated in a contemporary study that included five courses of high-dose MTX and 13 to 25 doses of triple intrathecal therapy . Logistic regression modeling was used to evaluate clinical and pharmacokinetic factors , and a genome-wide association study ( GWAS ) was performed to identify germline polymorphisms for their association with neurotoxicities . RESULTS Fourteen patients ( 3.8 % ) developed MTX-related clinical neurotoxicity . Of 13 patients rechallenged with intrathecal and /or high-dose MTX , 12 did not experience recurrence of neurotoxicity . Leukoencephalopathy was found in 73 ( 20.6 % ) of 355 asymptomatic patients and in all symptomatic patients and persisted in 74 % of asymptomatic and 58 % of symptomatic patients at the end of therapy . A high 42-hour plasma MTX to leucovorin ratio ( measure of MTX exposure ) was associated with increased risk of leukoencephalopathy in multivariable analysis ( P = .038 ) . GWAS revealed polymorphisms in genes enriched for neurodevelopmental pathways with plausible mechanistic roles in neurotoxicity . CONCLUSION MTX-related clinical neurotoxicity is transient , and most patients can receive subsequent MTX without recurrence of acute or subacute symptoms . All symptomatic patients and one in five asymptomatic patients develop leukoencephalopathy that can persist until the end of therapy . Polymorphisms in genes related to neurogenesis may contribute to susceptibility to MTX-related neurotoxicity BACKGROUND Dexamethasone is increasingly used as the steroid of choice in trials for st and ard risk children with acute lymphoblastic leukemia ( ALL ) . Improvements in event-free survival ( EFS ) have been attributed to lower CNS relapse rates , However , there are concerns that dexamethasone may be more toxic than previous conventional therapy with prednisone . Such toxicity raises questions about the implication s for child neuropsychological function and HRQOL . Patients participating in the UK ALL 99/01 trial were r and omized to receive dexamethasone or prednisone as their steroid in induction and maintenance chemotherapy . We compared the HRQOL and behavior in children r and omized to receive both these agents . PROCEDURE St and ardized question naires to assess parent and child HRQOL at 3 - 6 months after diagnosis ( T1 ) and 1 year later ( T2 ) completed by mothers in family homes . Forty-five mothers of a child with ALL ( 32 male , 13 female ; average age at T1 , 7 years 3 months ; at T2 , 8 years 3 months ) completed HRQOL question naires . RESULTS For the total group , child HRQOL scores improved and behavior problems decreased significantly from T1 to T2 . Comparison of HRQOL scores between the 17 children r and omized to dexamethasone and 28 children r and omized to prednisone showed no significant differences . The rate of improvement in HRQOL from T1 to T2 did not differ between children r and omized to dexamethasone or prednisone . CONCLUSIONS Dexamethasone is increasingly used in the treatment of ALL and has been linked with improved survival rates . Long-term use of dexamethasone raises questions about neuropsychologic toxicity . Although HRQOL increased significantly over the year for all children , the extent of this increase did not differ by chemotherapy . These results should contribute to lessened concerns about use of dexamethasone in the treatment of ALL Multidimensional measurement of pediatric cancer patients ' health‐related quality of life ( HRQOL ) in Phase III r and omized controlled clinical trials is being recognized increasingly as an essential component in evaluating the comprehensive health outcomes of modern antineoplastic treatment protocol s. The Pediatric Cancer Quality of Life Inventory‐32 ( PCQL‐32 ) is a st and ardized patient self‐report and parent proxy‐report assessment instrument design ed to assess systematic ally pediatric cancer patients ' HRQOL outcomes This prospect i ve study describes the procedure‐related anxiety , treatment‐related anxiety , pain , and nausea experienced by children with st and ard‐risk acute lymphoblastic leukemia ( ALL ) during the first year of treatment |
13,521 | 16,856,087 | While the choice between DPMA and NET-EN as injectable progestogen contraceptives may vary between both health providers and patients , data from r and omized controlled trials indicate little difference between the effects of these methods , except that women on DMPA are more likely to develop amenorrhoea .
There is inadequate data to detect differences in some non-menstrual major and minor clinical effects | BACKGROUND There are two injectable progestogen-only contraceptives ( IPCs ) that have been available in many countries in the world since 1983 .
They are both still extensively used in many developing countries , forming a large proportion of the health system 's expenditure on contraception .
These are depot medroxyprogesterone acetate ( DMPA ) and norethisterone oenanthate ( NET-EN ) .
These are both highly effective contraceptives that receive wide acceptance amongst women in their fertile years .
They differ in frequency of administration that has implication s on patient uptake .
They also differ in cost that may significantly affect budgeting in the health system .
A systematic comparison will aid to ensure their rational use .
OBJECTIVES To determine if there are differences between depot medroxyprogesterone acetate given at a dose of 150 mg IM every 3 months and norethisterone oenanthate given at a dose of 200 mg IM every 2 months , in terms of contraceptive effectiveness , reversibility and discontinuation patterns , minor effects and major effects . | INTRODUCTION This 7-year , prospect i ve , matched-cohort , clinical study evaluated the effects of intramuscular depot medroxyprogesterone acetate ( DMPA ) ( 150 mg/mL ) on bone mineral density ( BMD ) in women aged 25 - 35 years . METHODS Bone mineral density changes in new DMPA-IM users ( n=248 ) were compared with those in women using nonhormonal contraception ( n=360 ) for up to 240 weeks of treatment and 96 weeks of posttreatment follow-up ( in subjects receiving > or=1 dose ) . RESULTS At week 240 of treatment , mean percentage changes from baseline in DMPA-IM vs. nonhormonal subjects were : -5.16 % ( n=21 ) vs. + 0.19 % ( n=65 ) , total hip ( p<.001 ) ; -5.38 % ( n=33 ) vs. + 0.43 % ( n=105 ) , lumbar spine ( p<.001 ) . At week 96 posttreatment , these values were : -0.20 % ( n=25 ) vs. + 0.84 % ( n=43 ) , total hip ( p=.047 ) ; -1.19 % ( n=41 ) vs. + 0.47 % ( n=66 ) , lumbar spine ( p=.017 ) . CONCLUSIONS These results show BMD declines during DMPA-IM use ; following discontinuation , significant increases in BMD occur through 96 weeks posttreatment A r and omized , single blind comparative trial of norethindrone enanthate ( NET-ENT ) and depo-medroxyprogesterone acetate ( DMPA ) was conducted in the Model Clinic , Decca , Bangladesh , to determine if there were differences in reported side effects , reasons for discontinuation and discontinuation rates of these two injectables . On all follow-up visits the proportion of women reporting no bleeding ( amenorrhea ) was higher for the DMPA clients compared to the NET-ENT clients . Concurrent with these findings , the proportion of women reporting irregular bleeding was consistently higher for the NET-ENT clients . Concurrent with these findings , the proportion of women reporting irregular bleeding was consistently higher for the NET-ENT clients compared to those receiving DMPA . By the fourth injection , less than 15 % of the clients in both drug groups still reported having regular cyclic bleeding ( 4 of the 26 DMPA clients and 4 of the 28 NET-ENT clients ) . Five of the 133 women on DMPA and 6 of the 106 women on NET-ENT became pregnant while using the injectables . At the end of one year of follow-up , 14 of the 133 DMPA and 14 of the 106 NET-ENT clients were still continuing ( came back for a fifth injection ) Final results are presented from a two-year WHO multinational comparative trial of three regimens : depot-medroxyprogesterone acetate ( DMPA ) given at 90-day intervals , norethisterone enanthate ( NET-EN ) given at 60-day intervals for the entire study period ( NET-EN ( 60-day ) ) , and NET-EN given at 60-day intervals for six months and thereafter at 84-day intervals ( NET-EN ( 84-day ) ) . 1587 DMPA subjects were observed for 20,550 woman-months , 789 NET-EN ( 60-day ) subjects were observed for 10,361 woman-months , and 796 NET-EN ( 84-day ) subjects were observed for 10,331 woman-months . This clinical trial represents the largest clinical trial undertaken on injectable contraceptives . After two years , the pregnancy rate with NET-EN ( 84-day ) was 1.4 ( + /- 0.6 S.E. ) per 100 women , as compared with the two-year rates of 0.4 ( + /- 0.3 S.E. ) per 100 women observed with DMPA and 0.4 ( + /- 0.2 S.E. ) with NET-EN ( 60-day ) . Both discontinuation rates for amenorrhea and the prevalence of amenorrhea lasting more than 90 days were significantly higher with DMPA than with either NET-EN regimen . Terminations for bleeding problems were similar with the three treatments , despite a better cyclic pattern for the first six months with the NET-EN regimens . The three treatments were comparable with respect to discontinuation rates for other medical or personal reasons , and for all reasons combined . For family planning programs , NET-EN ( 60-day ) has the advantage of low pregnancy rates compared to NET-EN ( 84-day ) , and a schedule of administration that does not change . Both NET-EN regimens produce less amenorrhea than DMPA . However , the NET-EN ( 60-day ) regimen has the logistic and economic disadvantage of requiring more frequent injections . All three injectable regimens compare favourably with oral contraceptives in terms of pregnancy and total continuation rates observed in clinical trial setting OBJECTIVE This study aims to assess changes in bleeding patterns with the use of depot medroxyprogesterone acetate ( DMPA ) 104 mg/0.65 ml subcutaneous injection ( DMPA-SC 104 ) . STUDY DESIGN An analysis was conducted using data from two 1-year , noncomparative clinical trials ( N=1787 ) and a 2-year r and omized study comparing DMPA-SC 104 ( N=266 ) with DMPA intramuscular injection ( DMPA-IM ) . Bleeding was analyzed per 30-day interval by category and number of days . Analyses also were performed for age and body mass index ( BMI ) subgroups and for the percentages of women shifting from bleeding/spotting to amenorrhea after each injection . RESULTS Each study showed decreased incidence of irregular bleeding and increased amenorrhea with continued use of DMPA-SC 104 . Rates of amenorrhea at Month 12 ( 52 - 64 % across studies ) and Month 24 ( 71 % in the 2-year trial ) were comparable with those originally reported for DMPA-IM . Changes in bleeding patterns showed no consistent differences according to age or BMI . The percentages of subjects shifting from bleeding and /or spotting to amenorrhea increased with each subsequent injection . CONCLUSION Clinical data show that the incidence of amenorrhea increases over time with the use of DMPA-SC 104 The acceptability of 2 and 3 month injectable contraceptives was assessed and compared , and the acceptability of the injectables was further compared with that of oral contraceptives ( OCs ) and IUDs among a r and om sample of women , who attended a clinic in Alex and ria , Egypt . The study was conducted by the University of Alex and ria . The sample included 100 acceptors of the 2-month injectable , norethisterone oenanthate ( NET-O EN ) , 100 acceptors of the 3-month injectable , depo-medroxy pregesterone acetate ( DPMA ) , 60 OC acceptors , and 60 IUD acceptors . The women were interviewed prior to treatment and 2 or 3 times during the 6 months following their initial acceptance of the methods . Women who discontinued at any time during the 6-month period were interviewed concerning their reasons for discontinuing . The data was analyzed by calculating means and % distribution and by testing for significance . The percent lost to follow up was 12 % for the NET-O EN group , 12 % for DPMA users , and 0 % for IUD and OC acceptors . The mean age of the acceptors was 30.4 years for NET-O EN , 30.7 years for DMPA , 28.3 years for OCs , and 25.2 years for IUDs . For these acceptor groups , the respective mean number of years of schooling was 6.1 , 5.2 , 7.2 , and 7.5 , and the respective mean number of pregnancies was 5.6 , 5.4 , 3.8 , and 2.9 . All 320 of the women were married , and 319 were Muslim . 99.4 % lived in urban areas . 10 % had no living male children , and 23.7 % had no living female children . 2/3 of the injectable acceptors previously used 2 or more fertility control methods . A higher percent of IUD and OC acceptors , compared to injectable acceptors , reported using only 1 or no previous method . More than 1/2 of the injectable acceptors reported disruptions in their normal bleeding patterns . NET-O EN acceptors were more likely to experience heavy or prolonged bleeding while DPMA acceptors were more likely to report amenorrhea or a decreased flow . IUD acceptors were also bothered by bleeding problems . Almost all the women who reported changes in bleeding patterns were unhappy about the changes . Many of the women who reported amenorrhea worried that they might be pregnant . Women who experienced heavy or unpredictable bleeding worried about anemia and complained that bleeding interfered with their daily routines . 47.6 % of the women reported weight gains , but this was generally viewed as an advantage . Nausea was the major side effect associated with OC use . 32 % of the OC users , 28.0 % of the NET-E ON users , 30.0 % of the DMPA users , and none of the IUD users reported nausea . For all 4 groups , convenience and effectiveness were the major advantages the women attributed to their chosen method . Continuation rates were 68 % for NET-O EN , 70 % for DMPA , 75 % for OCs , and 75 % for IUDs . The major reason for discontinuation of injectables was bleeding problems . Among injectable users , a higher proportion of discontinuers ( 49 % ) than of continuers ( 20 % ) reported amenorrhea . The findings suggest that continuation for injectables could be improved if patients were given more detailed information about possible side effects and if they were advised to return to the clinic for treatment of any symptoms they experience The present work was a r and omized comparative study of two injectable progestogen-only contraceptives . The first group ( 200 subjects ) received 150 mg of depotmedroxyprogesterone acetate ( Depoprovera ) every 84 + /- 7 days and the second ( 200 subjects ) received 200 mg of norethisterone enanthate ( Noristerat ) every 56 + /- 7 days . Acceptors of injectable contraceptives in Assiut , Egypt , were mainly women looking for fertility termination . Menstrual disruption was the main side effect among both treatment groups . Amenorrhoea was the commonest menstrual complaint and was the main reason for discontinuation in both groups . Only one pregnancy occurred during NET-EN use ; two more pregnancies occurred , one in each of the two groups but there were indications that conception preceded the first injection . Menstrual irregularities were generally more frequent with DMPA users . However , DMPA had better one-year continuation rates than NET-EN ( 68.8 + /- 3.5 and 57.1 + /- 3.6 per 100 women , respectively ) |
13,522 | 30,045,311 | Conclusions : The systematic review and meta- analysis suggests that the prognosis of male patients with coronary artery disease after percutaneous coronary intervention is better than that of females , except for long-term revascularization | Background and objectives : Previous research es have reported the controversial results regarding the gender difference in clinical outcomes of patients with coronary artery disease after percutaneous coronary intervention .
Hence , this systematic review and meta- analysis was design ed to investigate whether gender difference existed in patients with coronary artery disease after percutaneous coronary intervention . | Background —Diagnosis of coronary artery disease in women is more difficult because of lower specificity of symptoms and diagnostic accuracy of noninvasive testing . We sought to examine the relationship between gender and cardiac biomarkers in patients with unstable angina (UA)/non – ST-segment elevation myocardial infa rct ion ( NSTEMI ) . Methods and Results —In the TACTICS-TIMI 18 , OPUS-TIMI 16 , and TIMI 11 studies , baseline sample s were analyzed in the Thrombolysis In Myocardial Infa rct ion ( TIMI ) biomarker core laboratory . We examined the relationship between gender and elevated biomarkers . Of 1865 patients from TACTICS-TIMI 18 , 34 % were women . Fewer women had elevated creatine kinase-MB or troponins , whereas more had elevated high-sensitivity C-reactive protein or brain natriuretic peptide . Presence of ST-segment deviation and TIMI risk scores were not significantly different . This pattern was confirmed in TIMI 11 and OPUS-TIMI 16 . The prognostic value of the markers in TACTICS-TIMI 18 was similar in women and men . When a multimarker approach was examined , a greater proportion of high-risk women were identified . Marker-positive patients of both genders had improved outcome with an invasive strategy ; however , marker-negative women appeared to have improved outcomes with a conservative strategy . Conclusions —In patients with UA/NSTEMI , there was a different pattern of presenting biomarkers . Men were more likely to have elevated creatine kinase-MB and troponins , whereas women were more likely to have elevated C-reactive protein and brain natriuretic peptide . This suggests that a multimarker approach may aid the initial risk assessment of UA/NSTEMI , especially in women . Further research is necessary to eluci date whether gender-related pathophysiological differences exist in presentation with acute coronary syndromes Background Several studies have suggested sex‐related differences in diagnostic and invasive therapeutic coronary procedures . Methods and Results Data from consecutive patients who were enrolled in the Coronary Angiography and PCI Registry of the German Society of Cardiology were analyzed . We aim ed to compare sex‐related differences in in‐hospital outcomes of patients undergoing percutaneous coronary intervention ( PCI ) for stable coronary artery disease , non‐ST elevation acute coronary syndromes , ST elevation myocardial infa rct ion , and cardiogenic shock . From 2007 until the end of 2009 data from 185 312 PCIs were prospect ively registered : 27.9 % of the PCIs were performed in women . Primary PCI success rate was identical between the sexes ( 94 % ) . There were no sex‐related differences in hospital mortality among patients undergoing PCI for stable coronary artery disease , non‐ST elevation acute coronary syndromes , or cardiogenic shock except among ST elevation myocardial infa rct ion patients . Compared to men , women undergoing primary PCI for ST elevation myocardial infa rct ion have a higher risk of in‐hospital death , age‐adjusted odds ratio ( 1.19 , 95 % CI 1.06‐1.33 ) , and risk of ischemic cardiac and cerebrovascular events ( death , myocardial infa rct ion , transient ischemic attack/stroke ) , ( age‐adjusted odds ratio 1.19 , 95 % CI 1.16‐1.29 ) . Furthermore , access‐related complications were twice as high in women , irrespective of the indication . Conclusions Despite identical technical success rates of PCI between the 2 sexes , women with PCI for ST elevation myocardial infa rct ion have a 20 % higher age‐adjusted risk of death and of ischemic cardiac and cerebrovascular events . Further research is needed to determine the reasons for these differences BACKGROUND Gender and age are non-modifiable factors influencing clinical outcomes in acute coronary syndromes ( ACS ) . There is evidence that coronary artery disease pathophysiology varies in women . We therefore evaluated the effect of age and gender on clinical outcomes in patients with ACS undergoing percutaneous coronary interventions ( PCI ) . METHODS Among 3178 ( 25 % female ) consecutive ACS patients who underwent PCI at Liverpool Hospital , Sydney from 2003 to 2010 , using femoral access in 98 % of cases , we determined late events including mortality , myocardial infa rct ion and bleeding according to Bleeding Academic Research Consortium ( BARC ) criteria . RESULTS Females compared with males were older ( median 68 vs. 60 years ; p<0.001 ) , and were more likely to have diabetes ( 30 % vs. 22 % p<0.001 ) , hypertension ( 62 % vs. 49 % , p<0.001 ) , anaemia ( 26 % vs. 15 % , p<0.001 ) , and renal impairment ( 43 % vs. 20 % , p<0.001 ) ; they were more likely to be non-smokers ( 19 % vs. 30 % , p<0.001 ) . Females had less class B2/C lesions ( 64 % vs.68 % , p=0.048 ) , but had more calcified lesions ( 20 % vs. 11 % , p<0.001 ) , and smaller stent diameters ( 2.75[2.5 - 3.0 ] vs. 3.0[2.75 - 3.5 ] mm , p<0.001 ) . Females had higher three-year mortality rates ( 11 % vs. 7.0 % , p=0.001 ) , and more type 2 - 5 BARC bleeding post-PCI ( 22 % vs. 16 % , p=0.003 ) . Among patients under 55 years ( n=988 ) , mortality and bleeding were higher in females ( 6.0 % vs. 3.0 % , p=0.028 ) and ( 26 % vs. 14 % , p=0.001 ) respectively . There was no effect of gender on mortality or bleeding in patients 55 years and over . However , on multivariable stepwise regression analysis , female gender was not an independent predictor of mortality , but was a significant predictor of bleeding ( OR=1.84 [ 95 % CI:1.38 - 2.45 ] , p<0.001 ) . CONCLUSION Bleeding and mortality were higher in younger females with ACS who underwent PCI . While females had more post-PCI bleeding events , which were associated with late mortality , gender per se was not an independent predictor for mortality There are conflicting reports in the literature regarding the role of sex on the in-hospital mortality of patients with acute myocardial infa rct ion . The objective of this study is to determine whether there are gender differences in in-hospital mortality and angiographic findings of patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) undergoing percutaneous coronary intervention ( PCI ) . We conducted a prospect i ve study of all patients admitted to University Hospital Center Split , Croatia with STEMI from 2004 to 2008 who underwent PCI . From March 2004 throughout September 2008 , 488 patients with STEMI underwent PCI ( 364 men , 74.6 % ; 124 women , 25.4 % ) . Compared with men , women were significantly older ( mean age , 67.3 vs. 60.3 years ; p < 0.001 ) . Men had a significantly higher proportion of circumflex artery occlusion ( 19.5 % vs. 10.5 % , p = 0.022 ) . A higher proportion of men had a multivessel disease than women ( 56.8 % vs. 41.9 % ; p = 0.004 ) . In-hospital mortality was significantly higher among women ( 11.3 % vs. 4.6 % ; p = 0.002 ) but after adjustment for the baseline difference in age , the female sex was not an independent predictor of in-hospital mortality ( adjusted OR 1.15 ; 95 % CI 0.82 - 1.84 ) . In men , occlusions of left anterior descending artery showed higher mortality rate than occlusions of other coronary arteries ( LM 0 % , LAD 7.3 % , Cx 2.8 % , RCA 0.7 % , p = 0.03 ) . According to our results female gender is not an independent predictor of in-hospital mortality after percutaneous coronary intervention . In men , occlusions of left anterior descending arteries are associated with higher mortality rate comparing to occlusions of other coronary arteries Women with non-ST-elevation acute coronary syndromes ( NSTACSs ) may have better outcomes than men , but the effect of NSTACSs in women undergoing percutaneous coronary intervention ( PCI ) has not been examined . We performed a prospect i ve , multicenter , cohort study of consecutive patients who underwent PCI for NSTACS and stable angina during 3 National Heart , Lung , and Blood Institute Dynamic Registry recruitment waves ( 1997 to 2002 ) to examine the effect of female gender on adverse clinical events after PCI or stable angina for NSTACS . The primary end point was the combined rate of death , myocardial infa rct ion , or rehospitalization for cardiac causes at 1 year . Compared with men with NSTACS ( n = 2,124 ) , women ( n = 1,338 ) were older and more often had hypertension , diabetes mellitus , and history of heart failure ( p < 0.001 for all ) , whereas multivessel disease was less frequent ( p < 0.01 ) . Procedural success and in-hospital adverse event rates were similar . Women with NSTACS had the highest 1-year rate of death/myocardial infa rct ion/cardiac rehospitalization compared with women with stable angina pectoris ( n = 462 ) or men ( n = 995 ; women with NSTACS 37.6 % , men with NSTACS 29.8 % , women with stable angina 29.4 % , men with stable angina 27.7 % , p < 0.001 ) . The higher rate remained after adjustment for differences in baseline characteristics ( adjusted hazard ratio 1.37 , 95 % confidence interval 1.20 to 1.56 ) . Among women , NSTACS conferred a significantly higher risk for adverse events compared with stable angina ( adjusted hazard ratio 1.41 , p = 0.001 ) , whereas the risk of adverse events was not different in men ( adjusted hazard ratio 1.05 , p = 0.5 ) . In conclusion , women undergoing PCI for NSTACS have a higher risk of major adverse cardiac events than men or women undergoing PCI for stable angina The incidence of adverse outcomes after percutaneous coronary intervention ( PCI ) is higher in women than in men . Statins reduce the likelihood of cardiovascular events arising in patients with coronary artery disease ( CAD ) , but the impact of gender difference on long-term outcomes of PCI for CAD under statin treatment has not been established . We prospect ively enrolled 3,580 consecutive patients with CAD who were treated by PCI at our institution between 2000 and 2011 . Among these , 2,009 ( 43.9 % ; male , n = 1619 ; female , n = 390 ) were under statin therapy at the time of PCI . We evaluated the incidence of major adverse cardiac events ( MACE ) including all-cause death and acute coronary syndrome ( ACS ) . Age was significantly more advanced and the prevalences of hypertension and chronic kidney disease were higher among the female , than the male patients . Low-density lipoprotein cholesterol levels were significantly higher in women than in men ( 111.5 ± 38.9 vs. 107.5 ± 3 3.9 mg/dL , p = 0.04 ) . During a median follow-up period of 6.3 years , MACE that occurred in 336 ( 16.7 % ) patients included 206 ( 10.2 % ) with all-cause death and 154 ( 7.7 % ) with ACS . The cumulative rate of MACE tended to be higher in women than in men but the difference did not reach significance ( 19.7 vs. 16.0 % ; p = 0.08 , log-rank test ) . Multivariable Cox regression analysis showed that being female was not associated with MACE after adjusting for age ( HR 1.22 ; 95 % CI 0.94–1.57 ; p = 0.13 ) and other variables ( HR 1.14 ; 95 % CI 0.86–1.49 ; p = 0.35 ) . Long-term clinical outcomes were comparable between male and female patients with coronary artery disease who were administered with statins and underwent PCI even though the baseline characteristics were worse among the females The present study assessed the impact of early administration of abciximab in female and male patients with ST-segment elevation myocardial infa rct ion ( STEMI ) transferred for primary angioplasty ( PPCI ) . Data were gathered for 1,650 consecutive patients with STEMI transferred for PPCI from hospital networks in seven countries in Europe from November 2005 to January 2007 ( the EUROTRANSFER Registry population ) . Among 1,086 patients who received abciximab , there were 186 women and 541 men who received abciximab early ( > 30 min before PPCI ) , and 86 women and 273 men treated with late abciximab . Female patients were high-risk individuals , with advanced age and increased rate of ischemic events . Early abciximab administration was associated with enhanced patency of the infa rct -related artery before PPCI , and improved epicardial flow after PPCI in both women and men . Early abciximab in women led to the decrease in ischemic events , including 30 day ( adjusted OR 0.26 , 95 % CI 0.10–0.69 , p = 0.007 ) and 1 year ( adjusted OR 0.37 , 95 % CI 0.16–0.84 , p = 0.017 ) mortality reduction . In contrast , the reduction in 30 day ( adjusted OR 0.69 , 95 % CI 0.35–1.39 , p = 0.27 ) and 1 year ( adjusted OR 0.68 , 95 % CI 0.38–1.22 , p = 0.19 ) mortality was not significant in men . The frequency of bleeding events was similar in the early abciximab group compared to the late abciximab group in both women and men . Early administration of abciximab improved patency of the infa rct -related artery before and after PPCI , and led to improved survival in female patients with STEMI Objectives : To determine the gender differences in cardiovascular risk profile and outcomes among patients undergoing percutaneous coronary intervention ( PCI ) . Methods : In a prospect i ve multicenter study of consecutive Middle Eastern patients managed with PCI from January 2013 to February 2014 in 12 tertiary care centers in Amman and Irbid , Jordan . Clinical and coronary angiographic features , and major cardiovascular events were assessed for both genders from hospital stay to 1 year . Results : Women comprised 20.6 % of 2426 enrolled patients , were older ( mean age 62.9 years versus 57.2 years ) , had higher prevalence of hypertension ( 81 % versus 57 % ) , diabetes ( 66 % versus 44 % ) , dyslipidemia ( 58 % versus 46 % ) , and obesity ( 44 % versus 25 % ) compared with men , p<0.001 . The PCI for ST-segment elevation myocardial infa rct ion was indicated for fewer women than men ( 23 % versus 33 % ; p=0.001 ) . Prevalence of single or multi-vessel coronary artery disease was similar in women and men . More women than men had major bleeding during hospitalization ( 2.2 % versus 0.6 % ; p=0.003 ) and at one year ( 2.5 % versus 0.9 % ; p=0.007 ) . There were no significant differences between women and men in mortality ( 3.1 % versus 1.7 % ) or stent thrombosis ( 2.1 % versus 1.8 % ) at 1 year . Conclusion : Middle Eastern women undergoing PCI had worse baseline risk profile compared with men . Except for major bleeding , no gender differences in the incidence of major adverse cardiovascular events were demonstrated Abstract Objectives : To investigate the impact of sex on clinical outcomes after drug-eluting stent ( DES ) implantation in real-world patients . Methods and results : A total number of 4720 patients ( 3365 males and 1355 females ) undergoing the second-generation cobalt-chromium sirolimus-eluting stent ( CoCr-SES ) implantation from the FOCUS registry were included in this analysis . The cumulative incidences of major adverse cardiovascular event ( MACE ) ( 1.5 % vs. 2.4 % ; p = .03 ) , cardiovascular death ( 0.5 % vs. 1.0 % ; p = .02 ) and target vessel revascularization ( TVR ) ( 0.3 % vs. 0.8 % ; p = .01 ) within six months were significantly higher in females and the risks of MACE ( adjusted hazard ratio [ HR ] 0.5 ( 0.3–0.9 ) ; p = .01 ) and TVR ( adjusted HR 0.1(0.0–0.5 ) ; p = .001 ) remained significant in multivariate analysis . Reversely , the cumulative incidences of MACE ( 5.4 % vs. 4.8 % ; p = .04 ) and any revascularization ( 5.1 % vs. 3.3 % ; p = .01 ) were significantly higher in males beyond six months and the risks of all-cause death ( adjusted HR 1.6 ( 1.1–2.5 ) ; p = .03 ) and cardiovascular death ( adjusted HR 1.9 ( 1.1–3.6 ) ; p = .03 ) turned out to be significant in multivariate analysis . Notes : All cumulative incidences were presented as male vs. female ; all HRs were calculated as male relative to female . Conclusions : Females were associated with higher risk of early adverse events , while , males were associated with higher risk of late adverse events . Key messages Females undergoing PCI are typically older , have more cardiovascular risk factors , while , males in need of PCI are more frequently associated with complex lesions . The overall three-year cumulative incidences of adverse events are not significantly different between males and females but numerically higher in males . Females are associated with significantly higher risks of MACE and TVR within six months , while , males are associated with significantly higher risk of all-cause mortality and cardiac mortality beyond 6 months Women have a higher risk of adverse outcomes after percutaneous coronary intervention ( PCI ) than men . However , in acute coronary syndrome ( ACS ) , long-term outcomes after contemporary PCI with drug-eluting stent ( DES ) have not been fully investigated . We aim ed to test the impact of gender on outcomes in patients with ACS after PCI with DES . We analyzed all patients with ACS from the prospect i ve NOBORI-2 trial who underwent PCI with a Nobori DES from 2008 through 2009 in 125 centers worldwide . End points of the study were target lesion failure , cardiac death , myocardial infa rct ion ( MI ) , and clinical ly driven target lesion revascularization , and major adverse cardiac events ( composite of cardiac death , MI , and target vessel revascularization ) at 1 year and yearly up to 5 years . There were 1,640 patients with ACS , 1,268 men ( 77 % ) and 372 women ( 23 % ) . Compared to men , women were 5 years older and more frequently had co-morbidities such as diabetes mellitus and hypertension . There were no gender differences for cardiac death ( 1.3 % vs 2.7 % ) , MI ( 2.1 % vs 3.2 % ) , or target lesion revascularization ( 2.6 % vs 3.8 % ) at 1 year after the procedure for men and women , respectively . The trend was the same at 2 years ( cardiac death 2.0 % vs 2.3 % , MI 2.5 % vs 3.5 % , target lesion revascularization 3.2 % vs 4.6 % ) . Target lesion failure rates were 4.5 % and 5.9 % at 1 year and 5.7 % and 7.3 % at 2 years in men and women , respectively ( p = NS ) . Multivariate analysis , which included age , hypertension , diabetes mellitus , and number of diseased vessels , showed that gender was not a predictor for outcome . There were no differences in bleeding or stent thrombosis rates . Relief from anginal symptoms was similar . The same rate of adherence to dual antiplatelet therapy was observed and reached 73 % at 1 year and 31 % at 2 years after the ACS event and PCI . In conclusion , although women had worse baseline characteristics , no differences in outcomes were observed between men and women treated for ACS with contemporary DES Previous r and omized trials have addressed the impact of gender on outcomes , showing worse results in women assigned to invasive strategies compared with men with non-ST-elevation ( NSTE ) acute coronary syndrome ( ACS ) . However , there is still a significant amount of controversy on strategies of treatment on the basis of gender . This study evaluated the impact of gender on treatment strategies and outcomes in patients with NSTE ACS in a high-volume , single-site tertiary center . We identified 1,197 consecutive patients with NSTE ACS ( 381 women , 816 men ) who underwent percutaneous coronary intervention during their index hospitalizations . Patients were stratified by gender and baseline clinical and angiographic characteristics , and in-hospital and 9-month clinical outcomes were compared between the 2 groups . There were clear differences in baseline characteristics between men and women with ACS at presentation . Women were , on average , slightly older than men , with more hypertension and morbid obesity , but there were no differences in racial background s or the prevalence of diabetes or dyslipidemia , nor were there treatment disparities in pharmacologic interventions . Women and men with ACS had similar rates of percutaneous coronary intervention on index admission . Women had a greater incidence of bleeding complications requiring blood transfusions . Overall , in-hospital and 9-month event-free survival were equivalent for the 2 genders . In conclusion , in this single-site observational study , patients with NSTE ACS who underwent angiography followed by percutaneous coronary intervention demonstrated no significant gender differences in treatment or in-hospital or 9-month event-free survival . From these results , interventional strategies should not be based on gender We evaluated the effects of myocardial perfusion after primary percutaneous coronary intervention ( PCI ) for acute myocardial infa rct ion ( AMI ) on gender-based mortality rates . Research has demonstrated a gender-specific response of cardiomyocytes to ischemia and a potential increase in myocardial salvage in women compared with men . Myocardial blush grade ( MBG ) , an angiographic surrogate of myocardial perfusion , is an independent predictor of early and late survival after AMI . Whether the incidence and prognosis of myocardial perfusion differs according to gender among patients with AMI undergoing PCI is unknown . MBG and short- and long-term mortality were evaluated in 1,301 patients ( male = 935 ; female = 366 ) with AMI r and omized to primary angioplasty ± abciximab versus stent ± abciximab . Following PCI , > 96 % of patients achieved final Thrombolysis In Myocardial Infa rct ion 3 flow , of which MBG 2/3 was present in 58.3 % of women versus 51.1 % of men ( p = 0.02 ) . Worse MBG was an independent predictor of mortality in women at 30 days ( 7.4 % for MBG 0/1 vs 2.4 % for MBG 2/3 , p = 0.04 ) and at 1-year ( 11.0 % for MBG 0/1 vs 3.4 % for MBG 2/3 , p = 0.01 ) ; however , MBG was not associated with differences in mortality for men . In conclusion , impaired myocardial perfusion following PCI for AMI , indicated by worse MBG , is an independent predictor of early and late mortality in women but not in men . These findings imply an enhanced survival benefit from restoring myocardial perfusion for women compared with men during primary angioplasty and may have clinical implication s for interventional strategies in women To determine gender differences and predictors of all-cause mortality ( 30 days and 1 year ) after percutaneous coronary intervention ( PCI ) in patients with stable angina pectoris and acute coronary syndrome ( non-ST-elevation myocardial infa rct ion/unstable angina pectoris and ST-elevation myocardial infa rct ion ) in the British Cardiovascular Intervention Society ( BCIS ) and Swedish Coronary Angiography and Angioplasty Registry ( SCAAR ) data sets , an analysis of prospect ively collected data from 2007 to 2011 was performed . In total , 458,261 patients ( BCIS : n = 368,492 [ 25.9 % women ] ; Sweden : n = 89,769 [ 27.2 % women ] ) who underwent PCI were included in this analysis . Using multiple regression analysis , in the BCIS registry , female gender was an independent predictor of all-cause mortality at 30 days ( odds ratio [ OR ] 1.15 , 95 % CI 1.10 to 1.22 , p < 0.0001 ) and at 1 year ( OR 1.08 , 95 % CI 1.04 to 1.12 , p < 0.0001 ) after PCI for all patients . Likewise , in the SCAAR registry , female gender was an independent predictor of all-cause mortality at 30 days ( OR 1.15 , 95 % CI 1.05 to 1.26 , p = 0.002 ) and 1 year ( OR 1.09 , 95 % CI 1.03 to 1.17 , p = 0.006 ) after PCI for all patients . In both data sets , there was no statistically significant interaction between age and gender for all-cause mortality at 30 days ( BCIS , p = 0.59 ; SCAAR , p = 0.40 ) and at 1 year ( BCIS , p = 0.11 ; SCAAR , p = 0.83 ) . In conclusion , despite advances in care , women compared with men continue to experience higher all-cause mortality after PCI for coronary artery disease . The patient 's age at the time of PCI remains a strong predictive factor of mortality in this population . Strategies and further research are warranted to better address the management of coronary artery disease in women with possibly earlier diagnosis and more tailored treatments Background Gender and complete revascularisation are known to affect mortality . The objective of this study was to analyse a gender difference in mortality with respect to complete revascularisation for multivessel disease after primary percutaneous coronary intervention ( PPCI ) in ST-elevation myocardial infa rct ion ( STEMI ) patients . Method In a prospect i ve consecutive cohort of 1472 patients presenting with STEMI for PPCI , between January 2006 and January 2010 , 832 patients with multivessel disease were analysed . The primary outcome was long-term mortality . Results Median follow-up was 3.3 ± 1.2 years . Complete revascularisation was performed less in females than in males ( 30 vs. 38 % ; p = 0.04 ) . At PPCI , women ( 27 % , n = 221 ) were ± 10 years older ( p = 0.001 ) , had more hypertension , renal failure and symptoms of heart failure ( all p < 0.01 ) . Cumulative long-term mortality with incomplete revascularisation was higher in females ( F : 30 vs. M : 15 % , p = 0.01 ) . After adjustment for baseline characteristics , complete revascularisation ( 0.84 ; 95 % CI 0.54–1.32 ) and gender ( 1.11 ; 95 % CI 0.73–1.69 ) lost significance . Also the gender-by-complete revascularisation interaction was not significant at long term . In women , age under 60 years independently predicted higher mortality ( HR 10.09 ; 95 % CI 3.08–33.08 ; p < 0.001 ) . Conclusion In STEMI patients with multivessel disease at PPCI , women under the age of 60 years had higher mortality , but in women older than 60 years comorbidity impacted the outcome of revascularisation strategy in the long term BACKGROUND R and omized , controlled trials have demonstrated the superiority of sirolimus-eluting stent ( SES ) implantation during primary percutaneous coronary intervention ( PCI ) , as opposed to bare-metal stents , in patients with ST-elevation myocardial infa rct ion ( STEMI ) . This study aim ed to test the hypothesis that clinical benefits of SES treatment were independent of gender in this setting . METHODS A total of 2042 patients with STEMI undergoing SES-based primary PCI were prospect ively enrolled into Shanghai Acute Coronary Event ( SACE ) registry ( 1574 men and 468 women ) . Baseline demographics , angiographic and PCI features , and in-hospital and 30-day major adverse cardiac events ( MACE ) were analyzed as a function of gender . RESULTS Compared with men , women were older and more frequently had hypertension , diabetes , and hypercholesterolemia . Use of platelet glycoprotein IIb/IIIa receptor inhibitor ( GPI , 65.5 % vs. 62.2 % , P = 0.10 ) and procedural success rate ( 95.0 % vs. 94.2 % , P = 0.52 ) were similar in both genders . In-hospital death and MACE occurred in 3.8 % and 7.6 % , and 4.5 % and 8.1 % in the male and female patients , respectively ( all P > 0.05 ) . At 30-day follow-up , survival ( 94.3 % vs. 93.8 % , P = 0.66 ) and MACE-free survival ( 90.2 % vs. 89.3 % , P = 0.52 ) did not significantly differ between men and women . After adjustment for differences in patient demographics , angiographic and procedural features , there were no significant difference in either in-hospital ( OR = 0.77 , 95%CI of 0.48 to 1.22 , P = 0.30 ) or 30-day mortality ( OR = 1.28 , 95%CI of 0.73 to 2.23 , P = 0.38 ) between women and men . CONCLUSION Despite more advanced age and clustering of risk factors in women , female patients with STEMI treated by SES-based primary PCI had similar in-hospital and short-term clinical outcomes as their male counterparts AIMS The relationship between the predictive performance of the TIMI risk score for STEMI and gender has not been evaluated in the setting of primary PCI ( pPCI ) . Here , we compared in-hospital mortality and predictive performance of the TIMI risk score between Belgian women and men undergoing pPCI . METHODS AND RESULTS In-hospital mortality was analysed in 8,073 ( 1,920 [ 23.8 % ] female and 6,153 [ 76.2 % ] male patients ) consecutive pPCI-treated STEMI patients , included in the prospect i ve , observational Belgian STEMI registry ( January 2007 to February 2011 ) . A multivariable logistic regression model , including TIMI risk score variables and gender , evaluated differences in in-hospital mortality between men and women . The predictive performance of the TIMI risk score according to gender was evaluated in terms of discrimination and calibration . Mortality rates for TIMI scores in women and men were compared . Female patients were older , had more comorbidities and longer ischaemic times . Crude in-hospital mortality was 10.1 % in women vs. 4.9 % in men ( OR 2.2 ; 95 % CI : 1.82 - 2.66 , p<0.001 ) . When adjusting for TIMI risk score variables , mortality remained higher in women ( OR 1.47 , 95 % CI : 1.15 - 1.87 , p=0.002 ) . The TIMI risk score provided a good predictive discrimination and calibration in women as well as in men ( c-statistic=0.84 [ 95 % CI : 0.809 - 0.866 ] , goodness-of-fit p=0.53 and c-statistic=0.89 [ 95 % CI : 0.873 - 0.907 ] , goodness-of-fit p=0.13 , respectively ) , but mortality prediction for TIMI scores was better in men ( p=0.02 for TIMI score x gender interaction ) . CONCLUSIONS In the Belgian STEMI registry , pPCI-treated women had a higher in-hospital mortality rate even after correcting for TIMI risk score variables . The TIMI risk score was effective in predicting in-hospital mortality but performed slightly better in men . The data base was registered with clinical trials.gov ( NCT00727623 ) AIMS To determine if female gender is an independent predictor of in-hospital mortality after percutaneous coronary intervention ( PCI ) for ST segment elevation myocardial infa rct ion ( STEMI ) . A higher early mortality rate after STEMI has been reported in women before the widespread use of PCI in STEMI . PCI improves the prognosis of STEMI , however , the effect of PCI in women in this setting is controversial . In a large regional prospect i ve registry , we examined the in-hospital mortality after PCI for STEMI . METHODS AND RESULTS The greater Paris area comprises 11 million inhabitants . Data from all PCIs performed in 41 centres is entered in a m and atory registry . In-hospital mortality is recorded in another hospital-based data base . From 2003 to 2007 , 16,760 patients were treated by PCI for STEMI < 24 hours ; 21.9 % were women . Female patients were significantly older than men , 69.7 ± 14.3 years versus 59.3 ± 13.0 years ( p<0.0001 ) . The rate of diabetes mellitus and cardiogenic shock were significantly higher in women versus men , respectively 19.0 % versus 15.6 % , p<0.0001 and 6.7 % versus 4.0 % , p<0.0001 . The success rate of PCI was significantly lower in women : 94.7 % versus 95.9 % , p=0.002 . In-hospital mortality was significantly higher in women 9.8 % versus 4.3 % , p<0.0001 and the impact of gender on mortality was significant only after the age of 75 . By multivariate analysis , female gender is associated with higher in-hospital mortality . CONCLUSIONS After PCI for STEMI , female gender is still an independent predictor of in-hospital mortality BACKGROUND Limited data are available for sex-based differences in Japanese patients with acute myocardial infa rct ion ( AMI ) undergoing primary percutaneous coronary intervention ( PCI ) . METHODS AND RESULTS The study patients comprised 1,197 women and 3,182 men who underwent primary PCI for AMI in 2005 - 2007 . Compared with the men , the women were significantly older , and had significantly longer onset-to-balloon time and lower rate of follow-up coronary angiography . In-hospital mortality was higher among women than men ( 8.7 % vs. 4.9 % , P<0.001 ) . Although the cumulative incidence of all-cause death at 3 years was also higher for women ( 17.7 % vs. 10.7 % , P<0.001 ) , the adjusted risk for all-cause death was comparable [ hazard ratio ( HR , women vs. men)=0.94 , 95 % confidence interval ( CI ) : 0.71 - 1.24 , P=0.66 ] . The incidence ( 12.1 % vs. 12.4 % , P=0.77 ) and the adjusted risk ( HR=0.99 , 95 % CI 0.78 - 1.24 , P=0.92 ) for any clinical ly-driven coronary revascularization were both comparable . However , regarding any non- clinical ly-driven coronary revascularization , the incidence ( 19.6 % vs. 27.8 % , P<0.001 ) and the adjusted risk ( HR=0.79 , 95 % CI 0.65 - 0.95 , P=0.012 ) were both lower in women relative to men . CONCLUSIONS In current Japanese clinical practice for AMI , onset-to-balloon time was significantly longer in women than in men . Female sex was associated with lower follow-up coronary angiography rate and lower incidence of any non- clinical ly-driven coronary revascularization , whereas the incidence of any clinical ly-driven coronary revascularization was comparable between the sexes BACKGROUND Unfavourable effect of female sex on short- and long-term clinical outcomes has been demonstrated in unselected ST-elevation acute myocardial infa rct ion ( STEMI ) patients ; the results are conflicting in patients who undergo primary percutaneous coronary intervention ( PPCI ) . The objective of this sub study was to determine whether there are sex-related differences in the 30-day and 1-year clinical outcomes and bleeding after PPCI for STEMI . METHODS We analyzed 2096 STEMI patients enrolled in the Risk Scoring Model to Predict Net Adverse Cardiovascular Outcomes After Primary Percutaneous Coronary Intervention ( RISK-PCI ) trial from February 2006 to December 2009 . Composite efficacy end point comprised all-cause mortality , nonfatal infa rct ion , and stroke . Safety end point was bleeding classified according to the Thrombolysis in Myocardial Infa rct ion ( TIMI ) criteria . Net adverse cardiovascular events included composite efficacy end point and total bleeding . RESULTS Women in our study were older and presented later than men . After adjustment for potential confounders , there was no difference between sexes with respect to the composite efficacy end point . A higher rate of total bleeding was observed in women ( adjusted odds ratio [ OR ] , 1.67 ; 95 % confidence interval [ CI ] , 1.07 - 2.61 at 30 days , adjusted OR , 1.63 ; 95 % CI , 1.08 - 2.47 at 1 year ) compared with men . Total bleeding was associated with increased mortality at 30 days ( OR , 4.87 ; 95 % CI , 2.79 - 8.47 ) and at 1 year ( OR , 4.43 ; 95 % CI , 2.79 - 7.02 ) after PPCI . CONCLUSIONS We did not find a significant sex-related difference with respect to the composite efficacy end point . Women had a higher rate of total bleeding which was associated with increased short- and long-term mortality . Specific measures aim ed at preventing bleeding in women might improve the prognosis of PPCI patients Women have higher bleeding complication and mortality rates after percutaneous coronary interventions ( PCI ) . The contribution of female gender to bleeding and mortality is poorly understood . We evaluated the effect of gender and bleeding on outcomes of patients treated with bivalirudin during PCI by performing a patient-level pooled analysis of 3 r and omized controlled trials ( the R and omized Evaluation in PCI Linking Angiomax to Reduced Clinical Events , Acute Catheterization and Urgent Intervention Triage strategY , and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infa rct ion ) comparing bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor ( GPI ) treatment in patients undergoing PCI . Of 14,784 patients , 7,413 patients received bivalirudin ( 1,870 women ) and 7,371 patients received heparin + GPI ( 1,910 women ) . Women had significantly higher 30-day non-coronary artery bypass grafting (CABG)-related major bleeding rates ( 7.6 % vs 3.8 % , p < 0.0001 ) . After multivariate adjustment , female gender increased the hazard of major bleeding by 80 % ( hazard ratio 1.80 , 95 % confidence interval 1.52 to 2.11 , p < 0.001 ) . Furthermore , women had a higher 1-year mortality rate ( 3.7 % vs 2.7 % , p = 0.002 ) than men ; 30-day major bleeding was the strongest independent predictor of 1-year mortality in women ( hazard ratio 2.48 , 95 % confidence interval 1.57 to 3.91 , p = 0.001 ) . Bivalirudin therapy in women reduced 30-day non-CABG-related major bleeding ( 5.6 % vs 9.7 % , p < 0.0001 ) and 1-year mortality ( 2.9 % vs 4.4 % , p = 0.02 ) compared to st and ard therapy . In conclusion , in this cohort of patients treated for acute coronary syndrome and ST-segment elevation myocardial infa rct ion , women have a near 2-fold increase in bleeding complications compared to men after PCI . Bleeding complications rather than gender is the strongest independent predictor of 1-year mortality in patients undergoing PCI . Furthermore , we observed a more pronounced clinical benefit in women treated with bivalirudin including a 44 % reduction in major bleeding and a significant reduction in mortality rates at 1 year OBJECTIVE The impact of gender on clinical course after ST-elevation myocardial infa rct ion ( STEMI ) is not fully understood . We prospect ively investigated whether there are gender-related differences in epicardial and myocardial tissue-level perfusion , both of which represent important prognostic determinants in STEMI patients undergoing primary percutaneous coronary intervention ( PPCI ) . METHODS A total of 594 consecutive non-selected STEMI patients undergoing PPCI were prospect ively enrolled . Primary end-point of the study was post-procedural epicardial and myocardial perfusion . Secondary end-points were the 30-day and 6-month composite occurrence of major adverse cardiac events ( MACE ) . RESULTS Women with STEMI had higher risk factor profiles than men . Although PPCI achieved equal rates of successful epicardial reperfusion , women tended to have impaired microvascular reperfusion as reflected by lower rates of normal TIMI myocardial perfusion grade ( P=0.007 ) and complete ST-segment resolution ( P=0.079 ) . After adjustment for the risk profiles , multivariable analysis showed that gender itself was not an independent predictor of impaired microvascular reperfusion . Both female gender and impaired myocardial reperfusion were independent predictors of 30-day MACE , whereas gender lost its prognostic significance for 6-month MACE . Multivariable analysis restricted to female patients identified incomplete ST-segment resolution as the strongest determinant of 30-day MACE . CONCLUSION The differences in microvascular reperfusion after PPCI between women and men are attributed to higher risk profiles in women . Both female gender and impaired myocardial reperfusion were independent predictors of 30-day outcomes after PPCI , emphasizing the importance of successful microvascular reperfusion in the women with STEMI |
13,523 | 31,911,395 | RESULTS Analysis of 33 trials reporting treatment effects on all three outcomes showed reasonably strong association between treatment effects on PFS and OS , however the association parameters were obtained with a large uncertainty .
A weak surrogate relationship was noted between the treatment effects on TR and OS .
Modelling the two surrogate endpoints , TR and PFS , jointly as predictors of treatment effect on OS gave no marked improvement to surrogate association patterns .
Modest improvement in the precision of the predicted treatment effects on the final outcome was noted in studies investigating anti-angiogenic therapy , however it was likely due to chance .
The joint use of two surrogate endpoints did not lead to marked improvement in the association between treatment effects on surrogate and final endpoints in advanced colorectal cancer | BACKGROUND Progression free survival ( PFS ) and tumour response ( TR ) have been investigated as surrogate endpoints for overall survival ( OS ) in advanced colorectal cancer ( aCRC ) , however their validity has been shown to be suboptimal .
In recent years , meta-analytic methods allowing for use of multiple surrogate endpoints jointly have been proposed .
Our aim was to assess if PFS and TR used jointly as surrogate endpoints to OS improve their predictive value . | Summary Background When cure is impossible , cancer treatment should focus on both length and quality of life . Maximisation of time without toxic effects could be one effective strategy to achieve both of these goals . The COIN trial assessed preplanned treatment holidays in advanced colorectal cancer to achieve this aim . Methods COIN was a r and omised controlled trial in patients with previously untreated advanced colorectal cancer . Patients received either continuous oxaliplatin and fluoropyrimidine combination ( arm A ) , continuous chemotherapy plus cetuximab ( arm B ) , or intermittent ( arm C ) chemotherapy . In arms A and B , treatment continued until development of progressive disease , cumulative toxic effects , or the patient chose to stop . In arm C , patients who had not progressed at their 12-week scan started a chemotherapy-free interval until evidence of disease progression , when the same treatment was restarted . R and omisation was done central ly ( via telephone ) by the MRC Clinical Trials Unit using minimisation . Treatment allocation was not masked . The comparison of arms A and B is described in a companion paper . Here , we compare arms A and C , with the primary objective of establishing whether overall survival on intermittent therapy was non-inferior to that on continuous therapy , with a predefined non-inferiority boundary of 1·162 . Intention-to-treat ( ITT ) and per- protocol analyses were done . This trial is registered , IS RCT N27286448 . Findings 1630 patients were r and omly assigned to treatment groups ( 815 to continuous and 815 to intermittent therapy ) . Median survival in the ITT population ( n=815 in both groups ) was 15·8 months ( IQR 9·4–26·1 ) in arm A and 14·4 months ( 8·0–24·7 ) in arm C ( hazard ratio [ HR ] 1·084 , 80 % CI 1·008–1·165 ) . In the per- protocol population ( arm A , n=467 ; arm C , n=511 ) , median survival was 19·6 months ( 13·0–28·1 ) in arm A and 18·0 months ( 12·1–29·3 ) in arm C ( HR 1·087 , 0·986–1·198 ) . The upper limits of CIs for HRs in both analyses were greater than the predefined non-inferiority boundary . Preplanned subgroup analyses in the per- protocol population showed that a raised baseline platelet count , defined as 400 000 per μL or higher ( 271 [ 28 % ] of 978 patients ) , was associated with poor survival with intermittent chemotherapy : the HR for comparison of arm C and arm A in patients with a normal platelet count was 0·96 ( 95 % CI 0·80–1·15 , p=0·66 ) , versus 1·54 ( 1·17–2·03 , p=0·0018 ) in patients with a raised platelet count ( p=0·0027 for interaction ) . In the per- protocol population , more patients on continuous than on intermittent treatment had grade 3 or worse haematological toxic effects ( 72 [ 15 % ] vs 60 [ 12 % ] ) , whereas nausea and vomiting were more common on intermittent treatment ( 11 [ 2 % ] vs 43 [ 8 % ] ) . Grade 3 or worse peripheral neuropathy ( 126 [ 27 % ] vs 25 [ 5 % ] ) and h and –foot syndrome ( 21 [ 4 % ] vs 15 [ 3 % ] ) were more frequent on continuous than on intermittent treatment . Interpretation Although this trial did not show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in terms of overall survival , chemotherapy-free intervals remain a treatment option for some patients with advanced colorectal cancer , offering reduced time on chemotherapy , reduced cumulative toxic effects , and improved quality of life . Subgroup analyses suggest that patients with normal baseline platelet counts could gain the benefits of intermittent chemotherapy without detriment in survival , whereas those with raised baseline platelet counts have impaired survival and quality of life with intermittent chemotherapy and should not receive a treatment break . Funding Cancer Research UK PURPOSE To compare the efficacy of cediranib ( a vascular endothelial growth factor receptor tyrosine kinase inhibitor [ VEGFR TKI ] ) with that of bevacizumab ( anti-VEGF-A monoclonal antibody ) in combination with chemotherapy as first-line treatment for advanced metastatic colorectal cancer ( mCRC ) . PATIENTS AND METHODS HORIZON III [ Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Untreated Metastatic Colorectal Cancer ] had an adaptive phase II/III design . Patients r and omly assigned 1:1:1 received mFOLFOX6 [ oxaliplatin 85 mg/m(2 ) and leucovorin 400 mg/m(2 ) intravenously followed by fluorouracil 400 mg/m(2 ) intravenously on day 1 and then continuous infusion of 2,400 mg/m(2 ) over the next 46 hours every 2 weeks ] with cediranib ( 20 or 30 mg per day ) or bevacizumab ( 5 mg/kg every 14 days ) . An independent end-of-phase II analysis concluded that mFOLFOX6/cediranib 20 mg met predefined criteria for continuation ; subsequent patients received mFOLFOX6/cediranib 20 mg or mFOLFOX6/bevacizumab ( r and omly assigned 1:1 ) . The primary objective was to compare progression-free survival ( PFS ) . RESULTS In all , 1,422 patients received mFOLFOX6/cediranib 20 mg ( n = 709 ) or mFOLFOX6/bevacizumab ( n = 713 ) . Primary analysis revealed no significant difference between arms for PFS ( hazard ratio [ HR ] , 1.10 ; 95 % CI , 0.97 to 1.25 ; P = .119 ) , overall survival ( OS ; HR , 0.95 ; 95 % CI , 0.82 to 1.10 ; P = .541 ) , or overall response rate ( 46.3 % v 47.3 % ) . Median PFS and OS were 9.9 and 22.8 months for mFOLFOX6/cediranib and 10.3 and 21.3 months for mFOLFOX6/bevacizumab . The PFS upper 95 % CI was outside the predefined noninferiority limit ( HR < 1.2 ) . Common adverse events with more than 5 % incidence in the cediranib arm included diarrhea , neutropenia , and hypertension . Cediranib-treated patients completed fewer chemotherapy cycles than bevacizumab-treated patients ( median 10 v 12 cycles ) . Patient-reported outcomes ( PROs ) were significantly less favorable in cediranib-treated versus bevacizumab-treated patients ( P < .001 ) . CONCLUSION Cediranib activity , in terms of PFS and OS , was comparable to that of bevacizumab when added to mFOLFOX6 ; however , the predefined boundary for PFS noninferiority was not met . The cediranib safety profile was consistent with previous studies but led to less favorable PROs compared with bevacizumab . Investigation of oral TKIs in CRC continues BACKGROUND Cetuximab , an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor ( EGFR ) , has activity against colorectal cancers that express EGFR . METHODS From December 2003 to August 2005 , 572 patients who had colorectal cancer expressing immunohistochemically detectable EGFR and who had been previously treated with a fluoropyrimidine , irinotecan , and oxaliplatin or had contraindications to treatment with these drugs underwent r and omization to an initial dose of 400 mg of cetuximab per square meter of body-surface area followed by a weekly infusion of 250 mg per square meter plus best supportive care ( 287 patients ) or best supportive care alone ( 285 patients ) . The primary end point was overall survival . RESULTS In comparison with best supportive care alone , cetuximab treatment was associated with a significant improvement in overall survival ( hazard ratio for death , 0.77 ; 95 % confidence interval [ CI ] , 0.64 to 0.92 ; P=0.005 ) and in progression-free survival ( hazard ratio for disease progression or death , 0.68 ; 95 % CI , 0.57 to 0.80 ; P<0.001 ) . These benefits were robust after adjustment in a multivariable Cox proportional-hazards model . The median overall survival was 6.1 months in the cetuximab group and 4.6 months in the group assigned to supportive care alone . Partial responses occurred in 23 patients ( 8.0 % ) in the cetuximab group but in none in the group assigned to supportive care alone ( P<0.001 ) ; the disease was stable in an additional 31.4 % of patients assigned to cetuximab and in 10.9 % of patients assigned to supportive care alone ( P<0.001 ) . Quality of life was better preserved in the cetuximab group , with less deterioration in physical function and global health status scores ( both P<0.05 ) . Cetuximab treatment was associated with a characteristic rash ; a rash of grade 2 or higher was strongly associated with improved survival ( hazard ratio for death , 0.33 ; 95 % CI , 0.22 to 0.50 ; P<0.001 ) . The incidence of any adverse event of grade 3 or higher was 78.5 % in the cetuximab group and 59.1 % in the group assigned to supportive care alone ( P<0.001 ) . CONCLUSIONS Cetuximab improves overall survival and progression-free survival and preserves quality -of-life measures in patients with colorectal cancer in whom other treatments have failed . ( Clinical Trials.gov number , NCT00079066 [ Clinical Trials.gov ] . ) BACKGROUND The optimum use of cytotoxic drugs for advanced colorectal cancer has not been defined . Our aim was to investigate whether combination treatment is better than the sequential administration of the same drugs in patients with advanced colorectal cancer . METHODS In this open-label , r and omised , phase 3 trial , we r and omly assigned patients ( 1:1 ratio ) with advanced , measurable , non-resectable colorectal cancer and WHO performance status 0 - 2 to receive either first-line treatment with bolus ( 400 mg/m(2 ) ) and infusional ( 2400 mg/m(2 ) ) fluorouracil plus leucovorin ( 400 mg/m(2 ) ) ( simplified LV5FU2 regimen ) , second-line LV5FU2 plus oxaliplatin ( 100 mg/m(2 ) ) ( FOLFOX6 ) , and third-line LV5FU2 plus irinotecan ( 180 mg/m(2 ) ) ( FOLFIRI ) or first-line FOLFOX6 and second-line FOLFIRI . Chemotherapy was administered every 2 weeks . R and omisation was done central ly using minimisation ( minimisation factors were WHO performance status , previous adjuvant chemotherapy , number of disease sites , and centre ) . The primary endpoint was progression-free survival after two lines of treatment . Analyses were by intention-to-treat . This trial is registered at Clinical Trials.gov , NCT00126256 . FINDINGS 205 patients were r and omly assigned to the sequential group and 205 to the combination group . 161 ( 79 % ) patients in the sequential group and 161 ( 79 % ) in the combination group died during the study . Median progression-free survival after two lines was 10·5 months ( 95 % CI 9·6 - 11·5 ) in the sequential group and 10·3 months ( 9·0 - 11·9 ) in the combination group ( hazard ratio 0·95 , 95 % CI 0·77 - 1·16 ; p=0·61 ) . All six deaths caused by toxic effects of treatment occurred in the combination group . During first-line chemotherapy , significantly fewer severe ( grade 3 - 4 ) haematological adverse events ( 12 events in 203 patients in sequential group vs 83 events in 203 patients in combination group ; p<0·0001 ) and non-haematological adverse events ( 26 events vs 186 events ; p<0·0001 ) occurred in the sequential group than in the combination group . INTERPRETATION Upfront combination chemotherapy is more toxic and is not more effective than the sequential use of the same cytotoxic drugs in patients with advanced , non-resectable colorectal cancer . FUNDING Sanofi-Aventis France PURPOSE To determine whether irinotecan plus oxaliplatin ( mIROX ) is superior to irinotecan plus infusional 5-fluorouracil , leucovorin ( FUFIRI ) as first-line therapy of patients with metastatic colorectal cancer ( mCRC ) . PATIENTS AND METHODS A phase III , r and omised , open-label multicentre study compared st and ard treatment with FUFIRI ( irinotecan 80 mg/m(2 ) , 5-fluorouracil 2000 mg/m(2 ) , folinic acid 500 mg/m(2 ) weekly times 6 ) to mIROX using an identical schedule of irinotecan plus oxaliplatin 85 mg/m(2 ) applied on days 1 , 15 and 29 of a 7-week cycle . The primary end-point was progression-free survival ( PFS ) . RESULTS A total of 479 eligible patients were r and omly assigned . Progression-free survival was 7.2 months in the mIROX arm and 8.2 months in the FUFIRI arm [ hazard ratio=1.14 ; 95 % confidence interval ( CI ) 0.94 - 1.37 ; P=0.178 ] . Comparable results were also obtained for overall survival time with 19 months in the mIROX-arm and 22 months in the FUFIRI-arm ( hazard ratio=1.08 , P=0.276 ) . Both regimens induced an identical objective response rate ( ORR ) of 41 % , but disease control rate ( ORR plus stable disease ) was significantly greater in the FUFIRI group ( 81 % versus 68 % , P=0.001 ) . Most frequent grade s 1 - 4 side-effects of mIROX and FUFIRI treatment were nausea ( 80 % versus 73 % ) and delayed diarrhoea ( 79 % versus 68 % ) . Grade s 3 - 4 toxicities were generally below 10 % , except for diarrhoea which was more frequent in the mIROX-arm compared to the FUFIRI-arm ( 19 % versus 30 % , P=0.006 ) CONCLUSION mIROX failed to show superior activity compared to high-dose 5-FU/folinic acid plus irinotecan . Due to better tolerability the combination of high-dose 5-FU/folinic acid and irinotecan remains a st and ard of care in first-line treatment of metastatic colorectal cancer PURPOSE This trial was conducted to determine whether high-dose fluorouracil ( FU ) given as a weekly 24-hour infusion is more active than bolus FU + leucovorin ( LV ) , and whether high-dose infusional FU can be modulated by LV . PATIENTS AND METHODS A total of 497 patients with previously untreated metastatic colorectal cancer were r and omly assigned to receive bolus FU 425 mg/m2 intravenously + LV 20 mg/m2 on days 1 to 5 and repeated on day 28 ( FU + LV ) , or FU 2600 mg/m2 as a 24-hour infusion alone ( FU24h ) or in combination with 500 mg/m2 LV ( FU24h + LV)-all given weekly x6 followed by a 2-week rest period . Survival was the major study end point . RESULTS With a median follow-up of more than 3 years , survival did not differ among the treatment groups ( median FU + LV , 11.1 months [ 95 % CI , 10.2 to 15.0 months ] ; FU24h , 13.0 months [ 95 % CI , 10.4 to 15.4 months ] ; FU24h + LV , 13.7 months [ 95 % CI , 12.0 to 16.4 months ] ; P = .724 ) . Progression-free survival ( PFS ) was significantly longer for FU24h + LV ( median FU + LV , 4.0 months [ 95 % CI , 3.4 to 4.9 ] ; FU24h , 4.1 months [ 95 % CI , 3.4 to 5.0 ] ; FU24h + LV 5.6 months [ 95 % CI , 4.4 to 6.7 ] ; P = .029 ) . The response rates in the subgroup of patients with measurable disease were 12 % , 10 % , and 17 % for FU + LV , FU24h , and FU24h + LV , respectively ( not significant ) . Occurrence of grade 3 and 4 diarrhea was higher in the FU24h + LV arm ( 22 % ) compared with the FU24h ( 6 % ) or FU + LV ( 9 % ) arms ; however , stomatitis ( 11 % in FU + LV v 3 % in FU24h v 5 % in FU24h + LV arms ) and hematologic toxicity were higher in the bolus FU + LV arm . Global quality of life did not differ within the three arms . CONCLUSION Neither FU24h + LV nor FU24h prolong survival , relative to bolus FU + LV . Leucovorin increases PFS if added to FU24h , but increases toxicity PURPOSE We performed this phase III study to compare the irinotecan , leucovorin ( LV ) , and fluorouracil ( FU ) regimen ( FOLFIRI ) versus the oxaliplatin , LV , and FU regimen ( FOLFOX4 ) in previously untreated patients with advanced colorectal cancer . PATIENTS AND METHODS A total of 360 chemotherapy-naive patients were r and omly assigned to receive , every 2 weeks , either arm A ( FOLFIRI : irinotecan 180 mg/m(2 ) on day 1 with LV 100 mg/m(2 ) administered as a 2-hour infusion before FU 400 mg/m(2 ) administered as an intravenous bolus injection , and FU 600 mg/m(2 ) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [ LV5FU2 ] ) or arm B ( FOLFOX4 : oxaliplatin 85 mg/m(2 ) on day 1 with LV5FU2 regimen ) . RESULTS One hundred sixty-four and 172 patients were assessable in arm A and B , respectively . Overall response rates ( ORR ) were 31 % in arm A ( 95 % CI , 24.6 % to 38.3 % ) and 34 % in arm B ( 95 % CI , 27.2 % to 41.5 % ; P = .60 ) . In both arms A and B , median time to progression ( TTP ; 7 v 7 months , respectively ) , duration of response ( 9 v 10 months , respectively ) , and overall survival ( OS ; 14 v 15 months , respectively ) were similar , without any statistically significant difference . Toxicity was mild in both groups : alopecia and gastrointestinal disturbances were the most common toxicities in arm A ; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms , and no statistical significant difference was observed . CONCLUSION There is no difference in ORR , TTP , and OS for patients treated with the FOLFIRI or FOLFOX4 regimen . Both therapies seemed effective as first-line treatment in these patients . The difference between these two combination therapies is mainly in the toxicity profile BACKGROUND In advanced colorectal cancer , chemotherapy is usually administered without pauses and until progression but patients can experience cumulative toxicity and can not tolerate a heavy therapeutic charge . AIM The aim of the present trial was to evaluate whether an intermittent chemotherapy with levo-leucovorin + 5-fluorouracil ( 5-FU ) + irinotecan ( CPT-11 ) was at least as effective as the same regimen given continuously , both administered until progression , in patients affected with advanced colorectal cancer and not previously exposed to chemotherapy for metastatic disease . PATIENTS , MATERIAL S AND METHODS A total of 337 patients from 27 institutions were r and omised between levo-leucovorin , 100/mg/m(2 ) i.v . + 5-FU ; 400 mg/m(2 ) i.v . bolus + 5-FU ; 600 mg/m(2 ) 22-h continuous infusion , days 1 and 2 + CPT-11 ; 180 mg/m(2 ) day 1 , administered every 2 weeks 2 months on and 2 months off ( arm A ) and the same regimen administered continuously ( arm B ) , until progression in both arms . The main end point was overall survival ( OS ) , the secondary progression-free survival ( PFS ) and toxicity . RESULTS At a median follow-up of 41 months , OS was 18 months in arm A and 17 months in arm B [ hazard ratio ( HR ) , 0.88 ] . Also PFS was comparable in the two groups ( 6 months in both , with HR , 1.03 ) , and even grade s 3 - 4 toxicity ( mainly myelosuppression , fever and diarrhoea ) was similar . Second-line oxaliplatin-based treatment was administered in a similar percentage ( 66 % ) in the two arms . The median chemotherapy-free period ( drug holiday ) in arm A was 3.5 months . CONCLUSION Reducing the charge of therapy in this population did not diminish the efficacy of treatment . Further studies with this strategy , including biologicals , are warranted PURPOSE The clinical objective of this trial was to evaluate gefitinib in patients with metastatic colorectal cancer that had progressed despite prior treatment . Serial tumor biopsies were performed when possible and analyzed for activation of the epidermal growth factor receptor ( EGFR ) signaling pathway . Serial serum sample s were measured for amphiregulin and transforming growth factor-alpha ( TGFalpha ) . PATIENTS AND METHODS One hundred fifteen patients were r and omly assigned to receive gefitinib 250 or 500 mg orally once a day . One hundred ten patients were assessable for clinical efficacy . Biologic evaluation was performed on paired tumor sample s from 28 patients and correlated with clinical outcome . RESULTS Median progression-free survival was 1.9 months ( 95 % CI , 1.8 to 2.1 months ) and 4-month progression-free survival rate was 13 % + /- 5 % . One patient achieved a radiographic partial response ( RR = 1 % ; 95 % CI , 0.01 % to 5 % ) . Median survival was 6.3 months ( 95 % CI , 5.1 to 8.2 months ) . The most common adverse events were skin rash , diarrhea , and fatigue . In the biopsy cohort , expression of total or activated EGFR , activated Akt , activated MAP-kinase , or Ki67 did not decrease following 1 week of gefitinib . However , a trend toward decreased post-treatment levels of activated Akt and Ki67 was observed in patients with a PFS higher than the median , although these did not reach the .05 level of significance . CONCLUSION Gefitinib is inactive as a single agent in patients with previously treated colorectal cancer . In tumor sample s , gefitinib did not inhibit activation of its proximal target , EGFR . Trends were observed for inhibition of downstream regulators of cellular survival and proliferation in patients achieving longer progression-free survival PURPOSE The primary goal of this multicenter phase III trial was to determine whether overall survival ( OS ) of fluorouracil ( FU ) -refractory patients was noninferior when treated with second-line infusional fluorouracil , leucovorin , and oxaliplatin ( FOLFOX4 ; arm B ) versus irinotecan ( arm A ) . Cross-over to the other treatment on disease progression was m and ated . PATIENTS AND METHODS Patients who experienced treatment failure with one prior FU-based therapy and had not received prior irinotecan or oxaliplatin , either for metastatic disease or within 6 months of adjuvant FU therapy , were r and omly assigned to arm A ( irinotecan 350 or 300 mg/m(2 ) every 3 weeks ) or arm B ( FOLFOX4 ) . RESULTS A total of 491 patients were r and omly assigned ( arm A , n = 245 ; arm B , n = 246 ) ; 288 ( 59 % ) had experienced treatment failure with FU for metastatic colorectal cancer . Two hundred twenty-seven patients ( 46 % ) received protocol -m and ated third-line therapy ( arm A , 43 % ; arm B , 57 % ) . Median survival was 13.8 months ( 95 % CI , 12.2 to 15.0 months ) for initial treatment with FOLFOX4 and 14.3 months ( 95 % CI , 12.0 to 15.9 months ) for irinotecan ( P = .38 ; hazard ratio = 0.92 ; 95 % CI , 0.8 to 1.1 ) . Response rates ( RR ; 28 % v 15.5 % ; P = .0009 ) and time to progression ( TTP ; 6.2 v 4.4 months ; P = .0009 ) were significantly superior with FOLFOX4 . In the nonr and om subset of patients who crossed over , RR and TTP improvements with FOLFOX4 continued into third-line treatment . Irinotecan therapy was associated with more grade 3 nausea , vomiting , diarrhea , and febrile neutropenia ; FOLFOX4 was associated with more neutropenia and paresthesias . CONCLUSION In patients who experienced treatment failure with front-line FU therapy , OS does not significantly differ whether second-line therapy begins with irinotecan or FOLFOX4 . FOLFOX4 produces higher RR and longer TTP . Both arms had notable OS in patients who experienced treatment failure with first-line FU therapy |
13,524 | 27,943,422 | At present , pretransplant FDG-PET can not be recommended in aggressive non-Hodgkin lymphoma , because available studies suffer from major method ological flaws , and reported prognostic estimates are low ( i.e. , poor in newly diagnosed and moderate in refractory/relapsed aggressive non-Hodgkin lymphoma ) | This study aim ed to systematic ally review and meta-analyze the value of pretransplant FDG-PET in predicting outcome after autologous stem cell transplantation in aggressive non-Hodgkin lymphoma . | PURPOSE The International Prognostic Index ( IPI ) is widely used for risk stratification of patients with aggressive B-cell lymphoma . The introduction of rituximab has markedly improved outcome , and R-CHOP ( rituximab + cyclophosphamide , doxorubicin , vincristine , prednisone ) has become the st and ard treatment for CD20(+ ) diffuse large B-cell lymphoma . To investigate whether the IPI has maintained its power for risk stratification when rituximab is combined with CHOP , we analyzed the prognostic relevance of IPI in three prospect i ve clinical trials . PATIENTS AND METHODS In total , 1,062 patients treated with rituximab were included ( MabThera International Trial [ MInT ] , 380 patients ; dose-escalated regimen of cyclophosphamide , doxorubicin , vincristine , etoposide , and prednisone ( MegaCHOEP ) trial , 72 patients ; CHOP + rituximab for patients older than age 60 years [ RICOVER-60 ] trial , 610 patients ) . A multivariate proportional hazards modeling was performed for single IPI factors under rituximab on event-free , progression-free , and overall survival . RESULTS IPI score was significant for all three end points . Rituximab significantly improved treatment outcome within each IPI group result ing in a quenching of the Kaplan-Meier estimators . However , IPI was a significant prognostic factor in all three end points and the ordering of the IPI groups remained valid . The relative risk estimates of single IPI factors and their order in patients treated with R-CHOP were similar to those found with CHOP . CONCLUSION The effects of rituximab were superimposed on the effects of CHOP with no interactions between chemotherapy and antibody therapy . These results demonstrate that the IPI is still valid in the R-CHOP era BACKGROUND High-dose therapy ( HDT ) followed by transplantation of autologous haemopoietic stem cells is frequently done as part of first-line therapy in young patients with high-risk aggressive B-cell lymphoma . We investigated whether HDT with cytotoxic agents identical to those used for conventional therapy followed by autologous stem-cell transplantation ( ASCT ) improved survival outcome compared with conventional chemotherapy when rituximab was added to both modalities . METHODS We did an open-label , r and omised trial comparing conventional chemotherapy ( cyclophosphamide , doxorubicin , vincristine , etoposide , prednisone ) and rituximab ( R-CHOEP-14 ) with dose-escalated sequential HDT and rituximab ( R-MegaCHOEP ) followed by repetitive ASCT in high-risk ( age-adjusted International Prognostic Index [ IPI ] 2 or 3 ) patients aged 18 - 60 years with aggressive B-cell lymphoma . Eligible patients received radiotherapy for bulky , extranodal disease , or both . R and omisation ( 1:1 ) used the Pocock minimisation algorithm ; patients were stratified by age-adjusted IPI factors , bulky disease , and centre . The primary endpoint was event-free survival . All analyses were done on the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT00129090 . FINDINGS 136 patients were r and omly assigned to R-CHOEP-14 and 139 to R-MegaCHOEP . 130 patients in the R-CHOEP-14 group and 132 in the R-MegaCHOEP group were included in the intention-to-treat population . After a median of 42 months ( IQR 29 - 59 ) , 3-year event-free survival was 69·5 % ( 95 % CI 61·3 - 77·7 ) in the R-CHOEP-14 group and 61·4 % ( 52·8 - 70·0 ) in the R-MegaCHOEP group ( p=0·14 ; hazard ratio 1·3 , 95 % CI 0·9 - 2·0 ) . All 128 evaluable patients treated with R-MegaCHOEP had grade 4 leucopenia , as did 48 ( 58·5 % ) of 82 patients with documented blood counts in the R-CHOEP-14 group . All 128 evaluable patients in the R-MegaCHOEP group had grade 3 - 4 thrombocytopenia , as did 26 ( 33·8 % ) of 77 patients in the R-CHOEP-14 group with documented blood counts . The most important non-haematological grade 3 or 4 adverse event was infection , which occurred in 96 ( 75·0 % ) of 128 patients treated with R-MegaCHOEP and in 40 ( 31·3 % ) of 128 patients treated with R-CHOEP-14 . INTERPRETATION In young patients with high-risk aggressive B-cell lymphoma , R-MegaCHOEP was not superior to conventional R-CHOEP therapy and was associated with significantly more toxic effects . R-CHOEP-14 with or without radiotherapy remains a treatment option for these patients , with encouraging efficacy . FUNDING Deutsche Krebshilfe PURPOSE Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation ( ASCT ) is the st and ard treatment for relapsed diffuse large B-cell lymphoma ( DLBCL ) . Salvage regimens have never been compared ; their efficacy in the rituximab era is unknown . PATIENTS AND METHODS Patients with CD20(+ ) DLBCL in first relapse or who were refractory after first-line therapy were r and omly assigned to either rituximab , ifosfamide , etoposide , and carboplatin ( R-ICE ) or rituximab , dexamethasone , high-dose cytarabine , and cisplatin ( R-DHAP ) . Responding patients received high-dose chemotherapy and ASCT . RESULTS The median age of the 396 patients enrolled ( R-ICE , n = 202 ; R-DHAP , n = 194 ) was 55 years . Similar response rates were observed after three cycles of R-ICE ( 63.5 % ; 95 % CI , 56 % to 70 % ) and R-DHAP ( 62.8 % ; 95 CI , 55 % to 69 % ) . Factors affecting response rates ( P < .001 ) were refractory disease/relapse less than versus more than 12 months after diagnosis ( 46 % v 88 % , respectively ) , International Prognostic Index ( IPI ) of more than 1 versus 0 to 1 ( 52 % v 71 % , respectively ) , and prior rituximab treatment versus no prior rituximab ( 51 % v 83 % , respectively ) . There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival ( EFS ) or overall survival . Three-year EFS was affected by prior rituximab treatment versus no rituximab ( 21 % v 47 % , respectively ) , relapse less than versus more than 12 months after diagnosis ( 20 % v 45 % , respectively ) , and IPI of 2 to 3 versus 0 to 1 ( 18 % v 40 % , respectively ) . In the Cox model , these parameters were significant ( P < .001 ) . CONCLUSION In patients who experience relapse more than 12 months after diagnosis , prior rituximab treatment does not affect EFS . Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis , with no difference between the effects of R-ICE and R-DHAP 18F-fluorodeoxyglucose positron emission tomography ( FDG-PET ) documented response after salvage chemotherapy has been reported to impact survival in patients with aggressive non-Hodgkin ’s lymphoma , especially diffuse large B cell lymphoma ( DLBCL ) undergoing high dose chemotherapy and autologous SCT ( HDC auto-SCT ) . We review ed the impact of 19 different prognostic/predictive factors before salvage chemotherapy and post-salvage chemotherapy FDG-PET results in patients with aggressive lymphoma and developed an FDG-PET integrated model for post-HDC auto-SCT outcome . The Fine and Gray method for competing risk analysis and a regression model was used to assess the risk associated with different factors on outcome . Fifty-five patients had FDG-PET after salvage chemotherapy ; male 65 % , female 45 % , relapsed 55 % , refractory 45 % , DLBCL 82 % , T cell lymphoma 18 % , median age at auto-SCT 40 years , median follow-up 42.4 months . Multivariate analysis identified only positive FDG-PET ( P=0.04 ) and mediastinal involvement ( P=0.05 ) with higher hazard rate of disease-specific death ( model P=0.008 ) but only positive FDG-PET ( P=0.01 ) for disease-specific events ( persistent , progressive or relapsed disease ) . Cumulative incidence of disease-specific death for patients with 0 , 1 and 2 risk factors was 5 , 30 and 62 % , respectively ( P=0.01 ) . Our model is significant and showed an increasing risk of failure with mediastinal involvement and post-salvage positive FDG-PET BACKGROUND High-dose chemotherapy followed by autologous bone marrow transplantation is a therapeutic option for patients with chemotherapy-sensitive non-Hodgkin 's lymphoma who have relapses . In this report we describe a prospect i ve r and omized study of such treatment . METHOD A total of 215 patients with relapses of non-Hodgkin 's lymphoma were treated between July 1987 and June 1994 . All patients received two courses of conventional chemotherapy . The 109 patients who had a response to chemotherapy were r and omly assigned to receive four courses of chemotherapy plus radiotherapy ( 54 patients ) or radiotherapy plus intensive chemotherapy and autologous bone marrow transplantation ( 55 patients ) . RESULTS The overall rate of response to conventional chemotherapy was 58 percent ; among patients with relapses after chemotherapy , the response rate was 64 percent , and among those with relapses during chemotherapy , the response rate was 21 percent . There were three deaths from toxic effects among the patients in the transplantation group , and none among those in the group receiving chemotherapy without transplantation . The two groups did not differ in terms of prognostic factors . The median follow-up time was 63 months . The response rate was 84 percent after bone marrow transplantation and 44 percent after chemotherapy without transplantation . At five years , the rate of event-free survival was 46 percent in the transplantation group and 12 percent in the group receiving chemotherapy without transplantation ( P = 0.001 ) , and the rate of overall survival was 53 and 32 percent , respectively ( P = 0.038 ) . CONCLUSIONS As compared with conventional chemotherapy , treatment with high-dose chemotherapy and autologous bone marrow transplantation increases event-free and overall survival in patients with chemotherapy-sensitive non-Hodgkin 's lymphoma in relapse Second-line chemotherapy followed by high-dose therapy ( HDT ) with autologous stem cell transplantation ( ASCT ) cures less than half of the patients with relapsed or refractory diffuse large B-cell lymphoma ( DLBCL ) . Prognostic models capable of predicting outcome are essential . In 3 sequential clinical trials , conducted from January 1993 to August 2000 , we treated 150 patients with relapsed or primary refractory DLBCL with ifosfamide , carboplatin , and etoposide ( ICE ) chemotherapy followed by HDT/ASCT for patients with chemosensitive disease . We evaluated the age-adjusted International Prognostic Index at the initiation of second-line therapy ( sAAIPI ) as a predictor of progression-free survival ( PFS ) and overall survival ( OS ) . At a median follow-up of 4 years , the PFS and OS are 28 % and 34 % by intention to treat and 39 % and 45 % for only those patients with chemosensitive disease . Three risk groups with different PFS and OS were identified by the sAAIPI : low risk ( 0 factors ) , 70 % and 74 % ; intermediate risk ( 1 factor ) , 39 % and 49 % ; and high risk ( 2 or 3 factors ) , 16 % and 18 % ( P < .001 for both PFS and OS ) . The sAAIPI also predicts the PFS and OS for patients with ICEchemosensitive disease : low risk , 69 % and 83 % ; intermediate risk , 46 % and 55 % ; and high risk , 25 % and 26 % ( P < .001 PFS and OS ) . The sAAIPI predicts outcome for patients with relapsed or primary refractory DLBCL in both intent-to-treat and chemosensitive population s. This powerful prognostic instrument should be used to evaluate new treatment approaches and to compare results of different regimens Allogeneic SCT is an effective therapy for lymphoma . Reduced-intensity conditioning ( RIC ) reduces non-relapse mortality ( NRM ) associated with myeloablative conditioning but relapse rates are high when performed in active disease . This study was design ed to explore the safety and outcome of ibritumomab tiuxetan ( Zevalin ) combined with RIC in patients with advanced lymphoma . The study included 12 patients , median age 54 years ( 37–62 ) , with a median of four prior treatments ( 2–6 ) and active disease documented on PET – CT . Zevalin 0.4 mCi/kg was given on day −14 and fludarabine combined with BU ( n=6 ) or melphalan ( n=6 ) was started on day −6 . GVHD prevention was tapered 3 months after SCT to augment the graft-versus-lymphoma effect . All patients engrafted , a median of 14 days after SCT . Eighty-three percent achieved CR/PR . With a median follow-up of 21 months ( 12–37 ) , 2-year PFS is 33 % . Only three patients relapsed ; cumulative incidence 25 % . NRM was 42 % , predominantly due to acute GVHD . Zevalin – RIC is feasible with consistent engraftment , acceptable organ toxicity , but high rates of acute GVHD . The low incidence of relapse suggests augmented anti-lymphoma effect . Zevalin – RIC merits further study . Better results may be achieved in patients earlier in disease course and with longer duration of immune-suppression PURPOSE In studies of diffuse large B-cell lymphoma , positron emission tomography with [(18)F]fluorodeoxyglucose ( FDG-PET ) performed after two to four cycles of chemotherapy has demonstrated prognostic significance . However , some patients treated with immunochemotherapy experience a favorable long-term outcome despite a positive interim FDG-PET scan . To clarify the significance of interim FDG-PET scans , we prospect ively studied interim FDG-positive disease within a risk-adapted sequential immunochemotherapy program . PATIENTS AND METHODS From March 2002 to November 2006 , 98 patients at Memorial Sloan-Kettering Cancer Center received induction therapy with four cycles of accelerated R-CHOP ( rituximab + cyclophosphamide , doxorubicin , vincristine , and prednisone ) followed by an interim FDG-PET scan . If the FDG-PET scan was negative , patients received three cycles of ICE ( ifosfamide , carboplatin , and etoposide ) consolidation therapy . If residual FDG-positive disease was seen , patients underwent biopsy ; if the biopsy was negative , they also received three cycles of ICE . Patients with a positive biopsy received ICE followed by autologous stem-cell transplantation . RESULTS At a median follow-up of 44 months , overall and progression-free survival were 90 % and 79 % , respectively . Ninety-seven patients underwent interim FDG-PET scans ; 59 had a negative scan , 51 of whom are progression free . Thirty-eight patients with FDG-PET-positive disease underwent repeat biopsy ; 33 were negative , and 26 remain progression free after ICE consolidation therapy . Progression-free survival of interim FDG-PET-positive/biopsy-negative patients was identical to that in patients with a negative interim FDG-PET scan ( P = .27 ) . CONCLUSION Interim or post-treatment FDG-PET evaluation did not predict outcome with this dose-dense , sequential immunochemotherapy program . Outside of a clinical trial , we recommend biopsy confirmation of an abnormal interim FDG-PET scan before changing therapy Limited data exist about the role of second‐line chemotherapy response assessed by positron emission tomography ( PET ) as a prognostic factor in patients with aggressive non‐Hodgkin Lymphoma ( NHL ) who undergo autologous stem cell transplantation ( ASCT ) . The objective of this analysis was to investigate the main determinants of prognosis in patients with aggressive B‐cell NHL who undergo ASCT , focusing on the impact of pretransplantation PET , secondary age‐adjusted International Prognostic Index ( sAA‐IPI ) score , histology , and previous response to first‐line chemotherapy BACKGROUND Although many patients with intermediate- grade or high- grade ( aggressive ) non-Hodgkin 's lymphoma are cured by combination chemotherapy , the remainder are not cured and ultimately die of their disease . The Ann Arbor classification , used to determine the stage of this disease , does not consistently distinguish between patients with different long-term prognoses . This project was undertaken to develop a model for predicting outcome in patients with aggressive non-Hodgkin 's lymphoma on the basis of the patients ' clinical characteristics before treatment . METHODS Adults with aggressive non-Hodgkin 's lymphoma from 16 institutions and cooperative groups in the United States , Europe , and Canada who were treated between 1982 and 1987 with combination-chemotherapy regimens containing doxorubicin were evaluated for clinical features predictive of overall survival and relapse-free survival . Features that remained independently significant in step-down regression analyses of survival were incorporated into models that identified groups of patients of all ages and groups of patients no more than 60 years old with different risks of death . RESULTS In 2031 patients of all ages , our model , based on age , tumor stage , serum lactate dehydrogenase concentration , performance status , and number of extranodal disease sites , identified four risk groups with predicted five-year survival rates of 73 percent , 51 percent , 43 percent , and 26 percent . In 1274 patients 60 or younger , an age-adjusted model based on tumor stage , lactate dehydrogenase level , and performance status identified four risk groups with predicted five-year survival rates of 83 percent , 69 percent , 46 percent , and 32 percent . In both models , the increased risk of death was due to both a lower rate of complete responses and a higher rate of relapse from complete response . These two indexes , called the international index and the age-adjusted international index , were significantly more accurate than the Ann Arbor classification in predicting long-term survival . CONCLUSIONS The international index and the age-adjusted international index should be used in the design of future therapeutic trials in patients with aggressive non-Hodgkin 's lymphoma and in the selection of appropriate therapeutic approaches for individual patients PURPOSE To develop guidelines for performing and interpreting positron emission tomography ( PET ) imaging for treatment assessment in patients with lymphoma both in clinical practice and in clinical trials . METHODS An International Harmonization Project ( IHP ) was convened to discuss st and ardization of clinical trial parameters in lymphoma . An imaging subcommittee developed consensus recommendations based on published PET literature and the collective expertise of its members in the use of PET in lymphoma . Only recommendations subsequently endorsed by all IHP subcommittees were adopted . RECOMMENDATIONS PET after completion of therapy should be performed at least 3 weeks , and preferably at 6 to 8 weeks , after chemotherapy or chemoimmunotherapy , and 8 to 12 weeks after radiation or chemoradiotherapy . Visual assessment alone is adequate for interpreting PET findings as positive or negative when assessing response after completion of therapy . Mediastinal blood pool activity is recommended as the reference background activity to define PET positivity for a residual mass > or = 2 cm in greatest transverse diameter , regardless of its location . A smaller residual mass or a normal sized lymph node ( ie , < or = 1 x 1 cm in diameter ) should be considered positive if its activity is above that of the surrounding background . Specific criteria for defining PET positivity in the liver , spleen , lung , and bone marrow are also proposed . Use of attenuation-corrected PET is strongly encouraged . Use of PET for treatment monitoring during a course of therapy should only be done in a clinical trial or as part of a prospect i ve registry The effects of radiotherapy ( RT ) after chemotherapy in patients with diffuse large B-cell lymphoma ( DLBCL ) remain unclear ; several trials have yielded conflicting results . This study examined the effect of RT after cyclophosphamide , doxorubicin , vincristine , and prednisone + rituximab ( R-CHOP ) treatment on event-free ( EFS ) and overall ( OS ) survival . Data from 216 patients with DLBCL who were enrolled in two clinical trials at Italian Lymphoma Study Group sites and were subjected to six R-CHOP cycles and involved-field radiotherapy ( IFRT ) were retrospectively analyzed . IFRT treatment yielded significant EFS benefit , with a 66 % reduction in the risk of death and /or disease progression . Cox analysis , when adjusted for age , gender , stage , performance status ( PS ) , lactate dehydrogenase ( LDH ) , and disease bulk , confirmed the significant EFS benefit of IFRT . The role of RT in DLBCL in the rituximab era is unclear . Future studies must take into account new radiation techniques and the response to chemotherapy based on functional imaging . Prospect i ve r and omized trials incorporating response-adapted therapy and modern radiation techniques are needed BACKGROUND The efficacy of autologous stem-cell transplantation during the first remission in patients with diffuse , aggressive non-Hodgkin 's lymphoma classified as high-intermediate risk or high risk on the International Prognostic Index remains controversial and is untested in the rituximab era . METHODS We treated 397 patients who had disease with an age-adjusted classification of high risk or high-intermediate risk with five cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) or CHOP plus rituximab . Patients with a response were r and omly assigned to receive three additional cycles of induction chemotherapy ( control group ) or one additional cycle of induction chemotherapy followed by autologous stem-cell transplantation ( transplantation group ) . The primary efficacy end points were 2-year progression-free survival and overall survival . RESULTS Of 370 induction-eligible patients , 253 were r and omly assigned to the transplantation group ( 125 ) or the control group ( 128 ) . Forty-six patients in the transplantation group and 68 in the control group had disease progression or died , with 2-year progression-free survival rates of 69 and 55 % , respectively ( hazard ratio in the control group vs. the transplantation group , 1.72 ; 95 % confidence interval [ CI ] , 1.18 to 2.51 ; P=0.005 ) . Thirty-seven patients in the transplantation group and 47 in the control group died , with 2-year overall survival rates of 74 and 71 % , respectively ( hazard ratio , 1.26 ; 95 % CI , 0.82 to 1.94 ; P=0.30 ) . Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival ( P=0.04 for interaction ) and overall survival ( P=0.01 for interaction ) . Among high-risk patients , the 2-year overall survival rate was 82 % in the transplantation group and 64 % in the control group . CONCLUSIONS Early autologous stem-cell transplantation improved progression-free survival among patients with high-intermediate-risk or high-risk disease who had a response to induction therapy . Overall survival after transplantation was not improved , probably because of the effectiveness of salvage transplantation . ( Funded by the National Cancer Institute , Department of Health and Human Services , and others ; SWOG-9704 Clinical Trials.gov number , NCT00004031 . ) High‐dose chemotherapy combined with autologous stem‐cell transplantation ( ASCT ) is the st and ard therapy for refractory/relapsed aggressive lymphoma . In the era of rituximab‐containing frontline regimens , it is becoming more challenging to salvage patients in this setting , and novel approaches are required . This is a r and omized study evaluating the safety and efficacy of st and ard‐dose ibritumomab tiuxetan ( Zevalin ) combined with high‐dose BEAM chemotherapy ( Z‐BEAM ) and ASCT in refractory/relapsed aggressive lymphoma We evaluated the safety and efficacy of st and ard-dose yttrium-90 ( Y(90 ) ) ibritumomab tiuxetan combined with high-dose BEAM ( carmustine , etoposide , cytarabine , and melphalan ) after first-line induction treatment in young patients with poor prognoses diffuse large B cell lymphoma ( DLBCL ) ( clinical trials.gov : NCT00689169 ) . Seventy-five high-risk ( ≥2 International Prognostic Index [ IPI ] factors ) consecutive DLBCL patients ( ≤65 years old ) in complete remission ( CR ) or partial remission ( PR ) after rituximab chemotherapy were treated with Y(90 ) ibritumomab tiuxetan and BEAM regimen followed by autologous stem cell transplantation ( ASCT ) . The median follow-up was 34 months . Of the 75 patients , 71 underwent ASCT and were eligible for analysis . Median time to reach a neutrophil count of > 500/μL and platelet count of > 20,000/μL was 11 days . Mucositis ≥3 ( 51 % ) occurred in most patients . Other adverse events were similar to those seen with BEAM alone . The overall response rate was 86 % ; 59 patients ( 83 % ) achieved a CR or unconfirmed CR . The 2-year event-free survival ( EFS ) , overall survival ( OS ) , and disease-free survival were 79 % , 83 % , and 91 % , respectively . Disease status ( CR/PR ) and positron emission tomography ( PET ) findings before transplantation did not predict treatment failure . The IPI ( 2 versus > 2 ) and maximum tumor diameter of ≥10 cm at diagnosis appeared to be prognosis factors for OS but not for EFS . Adding Y(90 ) ibritumomab tiuxetan to BEAM is safe and does not increase transplantation-related toxicity . First-line consolidation with Y(90 ) ibritumomab tiuxetan and high-dose chemotherapy induced high rates of EFS and OS in poor-prognosis patients with DLBCL , regardless of PET status after induction treatment and warrants a r and omized study Current clinical and imaging tools remain suboptimal for early assessment of prognosis and treatment response in aggressive lymphomas . PET with 3′-deoxy-3′-18F-fluorothymidine ( 18F-FLT ) can be used to measure tumor cell proliferation and treatment response . In a prospect i ve study in patients with advanced-stage B-cell lymphoma , we investigated the prognostic and predictive value of 18F-FLT PET in comparison to st and ard imaging with 18F-FDG PET and clinical outcome . Methods : Sixty-five patients were treated with an induction/consolidation regimen consisting of 4 cycles of R-CHOP-14 ( rituximab , cyclophosphamide , doxorubicin , vincristine , prednisone ) followed by 3 cycles of ICE ( ifosfamide , carboplatin , etoposide ) . 18F-FLT PET was performed at baseline and at interim ( iPET ) after 1–2 cycles of therapy . 18F-FDG PET was performed at baseline , after cycle 4 , and at the end of therapy . The relationship between PET findings , progression-free survival ( PFS ) and overall survival ( OS ) was investigated . Results : With a median follow-up of 51 mo , PFS and OS were 71 % and 86 % , respectively . 18F-FLT iPET , analyzed visually ( using a 5-point score ) or semiquantitatively ( using SUV and ΔSUV ) predicted both PFS and OS ( P < 0.01 for all parameters ) . Residual 18F-FLT SUVmax on iPET was associated with an inferior PFS ( hazard ratio , 1.26 , P = 0.001 ) and OS ( hazard ratio , 1.27 , P = 0.002 ) . When 18F-FDG PET was used , findings in the end of treatment scan were better predictors of PFS and OS than findings on the interim scan . Baseline PET imaging parameters , including SUV , proliferative volume , or metabolic tumor volume , did not correlate with outcome . Conclusion : 18F-FLT PET after 1–2 cycles of chemotherapy predicts PFS and OS , and a negative 18F-FLT iPET result may potentially help design risk-adapted therapies in patients with aggressive lymphomas . In contrast , the positive predictive value of 18F-FLT iPET remains too low to justify changes in patient management |
13,525 | 25,600,902 | The nine heterogeneous studies on microelements and vitamins suggest vegan-vegetarian women may be at risk of vitamin B12 and iron deficiencies . | BACKGROUND Although vegan-vegetarian diets are increasingly popular , no recent systematic review s on vegan-vegetarian diets in pregnancy exist .
OBJECTIVES To review the literature on vegan-vegetarian diets and pregnancy outcomes . | Objectives : To investigate whether a modest number of food frequency questions are sufficient to describe sociodemographic differences in dietary habits , and to identify sociodemographic characteristics of subjects adhering to food-based dietary guidelines operationalised in a ‘ healthy-diet index ’ . Design : Cross-sectional population survey . Subjects : A total of 480 men , 515 women , aged 15–90 y. R and om sample of private telephone numbers drawn from regional telephone records , geographically stratified . Participation rate 62 % . Methods : Computer-assisted telephone interviews , including six food frequency questions , a question on type of fat spreads used on bread , questions on seven sociodemographic variables . Results : The summary of the healthy-diet index showed that the subjects who adhered to food-based dietary guidelines ( top quintile ) compared to those who did not ( bottom quintile ) were most often women ( odds ratio (OR)=6.07 ; confidence interval ( CI ) : 3.91–9.43 , women vs men ) , of older age ( OR=9.72 ; CI : 3.02–31.31 , old age vs young ) , highly educated ( OR=3.69 ; CI : 1.53–8.92 , high education vs low ) and living in multiperson households including children ( OR=4.66 ; CI : 2.47–8.80 , multiperson household vs single household ) . The results also showed that gender difference in dietary habits is associated with other sociodemographic variables . Conclusions : The selected food frequency questions proved sufficient to describe sociodemographic differences in dietary habits , and this method may be a valuable supplement to traditional quantitative dietary surveys in monitoring sociodemographic changes in eating patterns . The results also underline the influence of sociodemographic status on dietary habits . Sponsorship : The Danish Nutrition Council funded the study Background Vegetarian diets have been associated with lower risk of chronic disease , but little is known about the health effects of low meat diets and the reliability of self-reported vegetarian status . We aim ed to establish an analytical cohort over-represented with vegetarians , pescetarians and 1 day/week meat consumers , and to describe their lifestyle and dietary characteristics . In addition , we were able to compare self-reported vegetarians with vegetarians whose status has been confirmed by their response on the extensive food frequency question naire ( FFQ ) . Study methods Embedded within the Netherl and s Cohort Study ( n = 120,852 ; including 1150 self-reported vegetarians ) , the NLCS-Meat Investigation Cohort ( NLCS-MIC ) was defined by combining all FFQ-confirmed-vegetarians ( n = 702 ) , pescetarians ( n = 394 ) , and 1 day/week meat consumers ( n = 1,396 ) from the total cohort with a r and om sample of 2–5 days/week- and 6–7 days/week meat consumers ( n = 2,965 and 5,648 , respectively ) . Results Vegetarians , pescetarians , and 1 day/week meat consumers had more favorable dietary intakes ( e.g. higher fiber/vegetables ) and lifestyle characteristics ( e.g. lower smoking rates ) compared to regular meat consumers in both sexes . Vegetarians adhered to their diet longer than pescetarians and 1 day/week meat consumers . 75 % of vegetarians with a prevalent cancer at baseline had changed to this diet after diagnosis . 50 % of self-reported vegetarians reported meat or fish consumption on the FFQ . Although the misclassification that occurred in terms of diet and lifestyle when merely relying on self-reporting was relatively small , the impact on associations with disease risk remains to be studied . Conclusion We established an analytical cohort over-represented with persons at the lower end of the meat consumption spectrum which should facilitate prospect i ve studies of major cancers and causes of death using ≥20.3 years of follow-up The effects on pregnancy outcome and maternal iron status of powdered milk ( PUR ) and a milk-based fortified product ( V-N ) were compared in a group of underweight gravidas . These take-home products were distributed during regular prenatal visits . Women in the V-N group had greater weight gain ( 12.29 vs 11.31 kg , p less than 0.05 ) and mean birth weights ( 3178 vs 3105 g , p less than 0.05 ) than those in the PUR group . Values for various indicators of maternal Fe status were also higher in the V-N group . Compared with self-selected noncompliers , similar in all control variables to compliers , children of women who consumed powdered milk or the milk-based fortified product had mean birth weights that were higher by 258 and 335 g , respectively . Data indicate a beneficial effect of the fortified product on both maternal nutritional status and fetal growth The effect of increasing dietary folate on folate status during pregnancy is controversial . The aim of this study was to compare folate intake and folate status during pregnancy of women with high long-term vegetable intake and those eating an average Western diet . In a prospect i ve study that included 109 participants , pregnant women adhering to a predominant vegetarian diet with high vegetable intake for 8 + /- 0.5 y with subgroups of ovo-lacto vegetarians ( n = 27 ) and low meat eaters ( n = 43 ) and women eating an average Western diet ( control group , n = 39 ) were compared with regard to dietary intake and plasma and red blood cell ( RBC ) folate concentrations during wk 9 - 12 , 20 - 22 and 36 - 38 of gestation . Plasma and RBC folate concentrations were highest in ovo-lacto vegetarians , followed by low meat eaters and lowest in the controls . Ovo-lacto vegetarians and low meat eaters showed a lower risk for folate deficiency , with RBC folate concentrations of < 320 nmol/L result ing in odds ratios of 0.10 ( 95 % confidence interval , 0.01 - 0.56 ) and 0.52 ( 95 % confidence interval , 0.20 - 1.34 ) , respectively . In ovo-lacto vegetarians , the RBC folate concentration was positively related to the intake of vitamin B-12 ( r = 0.51 , P : < 0.0001 ) . The results of the study suggest that long-term high vegetable intake favorably affects plasma folate as well as RBC folate concentrations throughout pregnancy and reduces the risk of folate deficiency if an adequate vitamin B-12 supply is ensured This study is a r and omized controlled double-blind trial on the effects of nutrition supplement of pregnant and lactating women on their offspring . The study was conducted by the late Dr. Bacon Chow in 14 villages in Sui-Lin township , a farming area about 180 miles from Taipei , Taiwan . Two hundred ninety-four women were r and omly assigned to one of two treatment groups . The daily supplement for one group provided 800 kcal and 40 g of protein/day ; for the other group it only provided 80 kcal/day . Supplementation began after 3 wk of the delivery of a first study infant , continued throughout lactation , and through the pregnancy and lactation of a second study infant . Between group comparisons on the birth weight , number of low birth weight infants , or incidence of fetal deaths showed no statistically significant findings . However , the birth weight of the second study infant was statistically different and higher than that of the first study infant in the high supplement group . Moreover , in the low supplement group there was a correlation of 0.22 ( p = 0.06 ) between the change scores for birth weight from the first to the second study infant and the quantity of supplements consumed during the last trimester of pregnancy . There was also in this same group a significant slope in a linear regression of birth weight on total daily caloric intake during the 3rd trimester of pregnancy for the male second study infants . These findings are partly in agreement with findings from three other large supplementation studies in Colombia , Guatemala , and New York . In this study the findings indicate that caloric supplementation does result in a small yet statistically meaningful increment in birth weight within a population which is not nutritionally at risk BACKGROUND Few data exist for the effects of multiple micronutrient ( MM ) or food supplementation to undernourished pregnant women on their offsprings ' development . OBJECTIVE We aim ed to compare the effects on infant development of early ( 8 - 10 wk gestation ) or usual ( approximately 17 wk gestation ) supplementation with food and MM , 30 mg Fe + 400 microg folate , or 60 mg Fe + 400 microg folate . DESIGN A large , r and omized , controlled trial of pregnancy supplementation was conducted in Bangladesh . A sub sample of infants ( n = 2853 ) were assessed on 2 problem-solving tests ( support and cover tests ) , the motor index of the Bayley Scales of Infant Development , and Wolke 's behavior ratings at 7 mo of age . RESULTS There were no significant effects of any intervention in the group as a whole . However , infants of undernourished mothers [ body mass index ( BMI ; in kg/m2 ) < 18.5 ] who received early food supplementation performed slightly but significantly ( P = 0.035 ) better on the support test than did infants of mothers who received usual food supplementation ( z score : 0.17 ; 95 % CI : 0.01 , 0.33 ) . There were no benefits in infants of higher- BMI mothers ( P = 0.024 for BMI x food interaction ) . Children of low- BMI mothers who received MMs had slightly better motor scores ( z score : 0.28 ; 95 % CI : 0.08 , 0.48 ) and activity ratings ( z score : 0.24 ; 95 % CI : 0.037 , 0.45 ) than did those who received 30 mg Fe + 400 microg folate , whereas other children did not benefit ( P = 0.05 for both motor scores and BMI x micronutrients and for activity and BMI x micronutrients ) . CONCLUSIONS Small benefits from early food and MM supplementation were found in infants of low- BMI but not of high- BMI mothers . However , the benefits were of doubtful functional importance , and longer follow-up is required to determine programmatic implication BACKGROUND Iron deficiency during pregnancy is associated with adverse birth outcomes , particularly , if present during early gestation . Iron supplements are widely recommended during pregnancy , but evidence of their benefit in relation to infant outcomes is not established . This study was performed in the UK , where iron supplements are not routinely recommended during pregnancy , to investigate the association between iron intake in pregnancy and size at birth . METHODS From a prospect i ve cohort of 1274 pregnant women aged 18–45 years , dietary intake was reported in a 24-h recall administered by a research midwife at 12-week gestation . Dietary supplement intake was ascertained using dietary recall and three question naires in the first , second and third trimesters . RESULTS Of the cohort of pregnant women , 80 % reported dietary iron intake below the UK Reference Nutrient Intake of 14.8 mg/day . Those reported taking iron-containing supplements in the first , second and third trimesters were 24 , 15 and 8 % , respectively . Women with dietary iron intake > 14.8 mg/day were more likely to be older , have a higher socioeconomic profile and take supplements during the first trimester . Vegetarians were less likely to have low dietary iron intake [ odds ratio = 0.5 , 95 % confidence interval ( CI ) : 0.4 , 0.8 ] and more likely to take supplements during the first and second trimesters . Total iron intake , but not iron intake from food only , was associated with birthweight centile ( adjusted change = 2.5 centiles/10 mg increase in iron , 95 % CI : 0.4 , 4.6 ) . This association was stronger in the high vitamin C intake group , but effect modification was not significant . CONCLUSION There was a positive relationship between total iron intake , from food and supplements , in early pregnancy and birthweight . Iron intake , both from diet and supplements , during the first trimester of pregnancy was higher in vegetarians and women with a better socioeconomic profile OBJECTIVES The purpose of this project was to develop a detailed , in-home , prenatal nutrition intervention protocol for low-income women and to assess the effectiveness of the intervention in improving their dietary intake . A secondary objective was to identify predictors of infant birth weight . DESIGN A defined protocol was developed and nutritionists followed it to conduct in-home nutrition sessions that included nutrition assessment , education , counseling , and goal setting for low-income women during their pregnancies . A pre/post design was used to assess the effects of the nutrition program on dietary intake . A control group was used in evaluating the effect of the nutrition intervention on birth weight . SUBJECTS/ SETTING Forty low-income pregnant women selected r and omly by the county health department nursing staff completed the nutrition intervention . Twenty-six women were also selected to serve as a control group . INTERVENTION For women in the intervention group , in-home visits were conducted weekly for 4 weeks , followed by 2 monthly visits . The purpose of the in-home visits was to use the defined protocol , which included monitoring weight gain and providing individualized dietary intake assessment and nutrition education and counseling . MAIN OUTCOME MEASURES The primary outcome measures were change in dietary intake from preintervention to postintervention , mothers ' weight at time of delivery , and infant birth weight . STATISTICAL ANALYSIS PERFORMED Paired t tests were used to compare the women 's mean daily energy and nutrient intakes before and after the nutrition intervention . Correlation analysis identified relationships between infant birth weight and independent variables , and multiple stepwise regression analysis was used to identify variables that contributed to the variation in infant birth weight . Mean birth weight was compared in the intervention and control groups by means of a t test . A chi 2 test was used for categoric variables . RESULTS Comparison of dietary intakes before and after the intervention revealed significant increases in total energy ( 2,269 to 2,431 kcal , P < .05 ) , folate ( 345 to 412 micrograms , P < .01 ) , vitamin B-6 ( 2.1 to 2.5 mg , P < .01 ) , iron ( 17.5 to 21.2 mg , P < .01 ) , zinc ( 13.6 to 14.7 mg , P < .01 ) , and calcium ( 1,175 mg to 1,299 mg , P < .01 ) and significant ( P < .01 ) increases in daily servings from the vegetable group ( 1.5 + /- 1.0 to 2.2 + /- 1.1 serving per day ) and breads/grains groups ( 3.4 + /- 1.4 to 4.1 + /- 1.5 servings per day ) . There was no significant difference in mean birth weight between the intervention and control groups . Sixty-five percent of the variation in infant birth weight was accounted for by mother 's weight at time of delivery , pre-pregnancy body mass index , number of visits by the nutritionist , and change in energy intake from preintervention to postintervention . APPLICATIONS This defined , in-home , prenatal nutrition intervention protocol can be used by providers of prenatal nutrition services to document outcomes of prenatal nutrition care in high-risk women . Use of a defined protocol will facilitate collection of meaningful outcomes data by service providers BACKGROUND Pregnancy in CKD is an increasing challenge , considering also the paucity of therapeutic tools available in pregnant women . While theoretically interesting , the experience with low protein diets in pregnancy is limited . Aim of this feasibility study is to review our experience with supplemented vegetarian low protein diets in pregnancy , as a " rescue treatment " for severe CKD and /or proteinuria . METHODS Data were gathered prospect ively . Diet schema : proteins : 0.6 - 0.7 g/Kg/day , amino and chetoacid supplementation , 1 - 3 free meals/week . Compliance , side effects , biochemical data recorded at each visit ( at least twice monthly ) . RESULTS Between January 2000 and February 2010 , out of 168 pregnancies referred , 12 were managed by the diet ( 11 patients ; median age 33 , range 20 - 38 ) . One pregnancy was terminated ( patient 's choice ) ; the other 10 patients delivered 11 healthy babies . At referral , 2 patients were in stage 4 CKD , 4 in stage 3 , 4 had nephrotic proteinuria ( 3.6 - 6.3 g/day ) . One patient doubled serum creatinine ; none needed renal replacement therapy within 6 months from delivery . No patient complained of side effects , nor developed hyperkalemia or hypercalcaemia . Two babies from mothers in CKD stage 4 were small for gestational age ; 9/11 were delivered by caesarean section ( median gestational age 33 weeks : range 28 - 37 ; birth weight 935 - 2620 g ) within a policy of delivery in the presence of foetal growth impairment and /or worsening of proteinuria , GFR , hypertension or foetal conditions . All babies are well , 1 month , 7.5 years from delivery . CONCLUSION Our report suggests considering vegetarian diets as an additional tool in the management of pregnant CKD patients Unselective dietary protein energy supplementation of Asian mothers at Sorrento Maternity Hospital did not enhance intrauterine growth . The effect of selective supplementation was therefore studied . Forty-five mothers who at 28 weeks were known to be nutritionally at risk ( triceps increment less than or equal to 20 microns/week between 18 and 28 weeks ) received one of three supplements during the third trimester : ( a ) vitamins only -- a multivitamin sachet daily containing vitamins A , B , C , and D ; ( b ) energy--42 - 125 MJ ( 10 000 - 30 000 kcal ) , all from carbohydrate , plus vitamins ; ( c ) protein energy -- energy and vitamins as before , but with 5 - 10 % of energy from milk protein . Eighty-three mothers regarded as adequately nourished at 28 weeks also received one of the three supplements . In the nutritionally at-risk mothers the protein energy supplement was associated with a heavier crude birth weight and heavier weight for gestational age . Supplementation did not lead to improved intrauterine growth in those mothers who were adequately nourished . The differential effect of supplementation depending on the mothers ' nutritional state during the second trimester may explain apparently conflicting results of other studies where some have shown a substantial effect of supplementation and others only a small effect . This effect of intervention is further evidence that " poor nutrition " contributes to poor intrauterine growth in selected mothers , even in developed countries There is a serious lack of community-based information on low birthweight or intrauterine growth retardation from Pakistan . A community based prospect i ve study was conducted in four squatter settlements of Karachi , to examine the prevalence and risk factors for adverse pregnancy outcome . This paper reports on the prevalence and risk factors for intrauterine growth retardation ( < 10th percentile birthweight gestational age ) among 755 singleton births . The incidence of intrauterine growth retardation was 25.4 % ( 192 intrauterine growth retarded and 563 appropriate for gestational age ) . Major socioeconomic risk factors identified were low maternal education ( RR = 1.4 , 95 % CI = 1.0,2.1 ) and poor housing material ( RR = 1.7 , 95 % CI = 1.0,3.0 ) . Among the significant biologic factors , primiparity ( RR = 1.9 , 95 % CI = 1.4,2.7 ) , consanguinity ( RR = 1.4 , 95 % CI = 1.4,2.7 ) , consanguinity ( RR = 1.4 , 95 % CI = 1.1,1.8 ) , short birth to CI = 1.1,2.1 ) , short stature ( RR = 2.2 , 95 % CI = 1.6,3.0 ) , low maternal weight ( RR = 2.0 , 95 % CI = 1.6,2.5 ) and non-vegetarian diet ( RR = 2.3 , 95 % CI = 1.3,4.2 ) were especially important . Investigations to assess the adverse mortality and morbidity effects of intrauterine growth retardation are ongoing Abstract Objective : To test the efficacy in terms of birth weight and infant survival of a diet supplement programme in pregnant African women through a primary healthcare system . Design : 5 year controlled trial of all pregnant women in 28 villages r and omised to daily supplementation with high energy groundnut biscuits ( 4.3MJ/day ) for about 20 weeks before delivery ( intervention ) or after delivery ( control ) . Setting : Rural Gambia . Subjects : Chronically undernourished women ( twin bearers excluded ) , yielding 2047 singleton live births and 35 stillbirths . Main outcome measures : Birth weight ; prevalence of low birth weight ( < 2500 g ) ; head circumference ; birth length ; gestational age ; prevalence of stillbirths ; neonatal and postneonatal mortality . Results : Supplementation increased weight gain in pregnancy and significantly increased birth weight , particularly during the nutritionally debilitating hungry season ( June to October ) . Weight gain increased by 201 g ( P<0.001 ) in the hungry season , by 94 g ( P<0.01 ) in the harvest season ( November to May ) , and by 136 g ( P<0.001 ) over the whole year . The odds ratio for low birthweight babies in supplemented women was 0.61 ( 95 % confidence interval 0.47 to 0.79 , P<0.001 ) . Head circumference was significantly increased ( P<0.01 ) , but by only 3.1 mm . Birth length and duration of gestation were not affected . Supplementation significantly reduced perinatal mortality : the odds ratio was 0.47 ( 0.23 to 0.99 , P<0.05 ) for stillbirths and 0.54 ( 0.35 to 0.85 , P<0.01 ) for all deaths in first week of life . Mortality after 7 days was unaffected . Conclusion : Prenatal dietary supplementation reduced retardation in intrauterine growth when effectively targeted at genuinely at-risk mothers . This was associated with a substantial reduction in the prevalence of stillbirths and in early neonatal mortality . The intervention can be successfully delivered through a primary healthcare system . Key messages In developing countries chronic maternal undernutrition is a prime contributor to the birth of over 25 million low birthweight babies annually and to high rates of neonatal mortality . An absence of well design ed field trials has created uncertainty about the potential efficacy of maternal feeding programmes This large scale r and omised controlled trial shows that dietary supplementation in pregnancy can be highly effective in reducing the proportion of low birthweight babies and perinatal mortality Incorporating supplementary feeding into a rural primary healthcare system is feasible Late pregnancy is the period most amenable to Objective : To compare dietary magnesium intake and magnesium concentrations in serum , red blood cells ( RBC ) and urine during pregnancy of women habitually following a long-term plant-based diet and of women following an average Western ( control ) diet . Design : Prospect i ve study during pregnancy . Setting : Giessen , Germany . Subjects : Healthy pregnant women ( n=108 ) in their 9–12th , 20–22nd and 36–38th gestational week habitually following a plant-based diet for more than 3 y or an average Western diet . The vegetarians were subdivided into ovo-lacto vegetarians ( n=27 ) and low-meat eaters ( n=43 ) . Results : Significant higher dietary magnesium intakes were observed in pregnant women consuming a plant-based diet ( 508±14 mg/day for ovo – lacto vegetarians , P<0.001 and 504±11 mg/day for low-meat eaters , P<0.001 ) than in pregnant women consuming a control diet ( 412±9 mg/day ) . Serum magnesium concentrations were similar in all diet groups whereas RBC magnesium was slightly higher in low-meat eaters than in controls ( P=0.058 ) . Urinary magnesium excretion was higher in ovo-lacto vegetarians ( P=0.023 ) , followed by low-meat eaters ( P=0.017 ) when compared to the control group . During the third trimester of pregnancy , the frequency and the occurrence of calf cramps was lower in the plant-based diet group than in the control group ( P=0.004 and 0.008 ) . Conclusions : Owing to a higher dietary magnesium intake confirmed by higher urinary magnesium excretion , habitual plant-based diets result in a slightly improved magnesium status during pregnancy and reduce the frequency of calf cramps during the third trimester of pregnancy compared to an average Western diet . Therefore , plant-based diets during pregnancy can be recommended with regard to magnesium supply OBJECTIVES To evaluate whether a maternal vegetarian diet influences the essential fatty acid status of the newborn and whether this is related to outcome of pregnancy . DESIGN Dietary intake and the fatty acid composition of plasma phospholipids were determined in 24 South Asian vegetarian and 24 white omnivore non-pregnant premenopausal women r and omly selected from the general population of North London . Umbilical cords and cord blood were collected at delivery from 48 South Asian vegetarian women and 98 white omnivores from the same catchment area along with details of antenatal history and the outcome of pregnancy . The fatty acid composition of the cord arteries and that of cord plasma phospholipids were analysed in a subset of 32 pairs of subjects , who were matched for maternal age , gestational age , parity and sex of infant . RESULTS Intakes of linoleic acid ( 18:2n-6 ) expressed as proportion of the dietary energy and the ratio of linoleic to alpha-linolenic acid ( 18:3n-3 ) were higher in the vegetarian women , and eicosapentaenoic acid ( EPA , 20:5n-3 ) and docosahexaenoic acid ( DHA , 22:6n-3 ) were absent from their diets . The proportion of linoleic acid , as well as the absolute concentration , was greater and those of EPA and DHA were lower in plasma phospholipids , plasma free fatty acid and total plasma lipids of the vegetarians compared with the white subjects . The proportion of DHA was lower ( P > 0.001 ) but that of docosapentaenoic acid ( 22:5n-6 ) was greater ( P < 0.001 ) in cord those from the omnivores . The ratio of 20:3n-9/20:4n-6 was elevated in cord artery but not in cord plasma phospholipids in both groups . Early onset of labour and the duration of gestation was 5.6 days shorter . Birth weight , head circumference and length were lower in the infants born to South Asian vegetarians even after adjusting for maternal height , duration of gestation , parity , gender of infants and smoking habits . Multivariate analysis did not reveal any relationship between the proportions of DHA in plasma or cord artery phospholipids and the birthweight or head circumference of the infants . CONCLUSION This study demonstrates that vegetarians give birth to infants with less DHA in their plasma and cord artery phospholipids but this did not appear to be independently related to the outcome of pregnancy A dietary survey of 939 Swiss adults , r and omly selected from the population of Geneva and its surrounding communities , was performed according to the history method . A factor analysis , using average weekly intakes for 33 food variables , reveals three principal components of the diet : satiating capacity , healthfulness and culinary complexity . These characteristics , together with the energy content of the diet , were analysed for differences according to sex , age , relative weight index , birthplace , marital status and occupation . All of these sociodemographic variables influence some dimension of dietary habits . Alcohol consumption is positively associated with satiating , protein rich diets , but energy intake from foods does not significantly differ between various groups of abstainers and drinkers . Although the energy contribution of alcoholic beverages is globally additive , we suggest that cultural and societal norms may modulate the relationship of alcohol and diet The study attempted to determine if the bulk of dietary supplements given to pregnant women after midgestation affects fetal growth . 127 Zulu women were r and omly assigned to four groups , two of which received daily food supplements design ed to raise their energy , protein and vitamin intakes to levels recommended by the U.S. Food and Nutrition Board . One of these supplements had a high bulk , the other a low bulk . The third supplement contained only zinc and the fourth a placebo . Women in all four groups had a similar weight gain and length of gestation . Birth weights were from 6.5 to 9.5 % greater with the low bulk than with the other supplements |
13,526 | 24,759,952 | Preliminary evidence suggests that Tai Chi Chuan can be an unconventional form of cardiac rehabilitation , being an adjunctive therapy in the treatment of patients with stable coronary artery disease . | BACKGROUND Several studies have shown that Tai Chi Chuan can improve cardiac function in patients with heart disease .
OBJECTIVE To conduct a systematic review of the literature to assess the effects of Tai Chi Chuan on cardiac rehabilitation for patients with coronary artery disease . | Background —Tai Chi Chuan ( TTC ) exercise has beneficial effects on the components of physical condition and can produce a substantial reduction in the risk of multiple falls . Previous studies have shown that short term TCC exercise did not improve the scores in the single leg stance test with eyes closed and the sit and reach test . There has apparently been no research into the effects of TCC on total body rotation flexibility and heart rate responses at rest and after a three minute step test . Methods —In this cross sectional study , 28 male TCC practitioners with an average age of 67.5 years old and 13.2 years of TCC exercise experience were recruited to form the TCC group . Another 30 sedentary men aged 66.2 were selected to serve as the control group . Measurements included resting heart rate , left and right single leg stance with eyes closed , modified sit and reach test , total body rotation test ( left and right ) , and a three minute step test . Results —Compared with the sedentary group , the TCC group had significantly better scores in resting heart rate , three minute step test heart rate , modified sit and reach , total body rotation test on both right and left side ( p<0.01 ) , and both right and left leg st and ing with eyes closed ( p<0.05 ) . According to the American Fitness St and ards , the TCC group attained the 90th percentile rank for sit and reach and total body rotation test , right and left . Conclusion —Long term regular TCC exercise has favourable effects on the promotion of balance control , flexibility , and cardiovascular fitness in older adults Of 22 r and omized trials of rehabilitation with exercise after myocardial infa rct ion ( MI ) , one trial had results that achieved conventional statistical significance . To determine whether or not these studies , in the aggregate , show a significant benefit of rehabilitation after myocardial infa rct ion , we performed an overview of all r and omized trials , involving 4,554 patients ; we evaluated total and cardiovascular mortality , sudden death , and fatal and nonfatal reinfa rct ion . For each endpoint , we calculated an odds ratio ( OR ) and 95 % confidence interval ( 95 % CI ) for the trials combined . After an average of 3 years of follow-up , the ORs were significantly lower in the rehabilitation than in the comparison group : specifically , total mortality ( OR = 0.80 [ 0.66 , 0.96 ] ) , cardiovascular mortality ( OR = 0.78 [ 0.63 , 0.96 ] ) , and fatal reinfa rct ion ( OR = 0.75 [ 0.59 , 0.95 ] ) . The OR for sudden death was significantly lower in the rehabilitation than in the comparison group at 1 year ( OR = 0.63 [ 0.41 , 0.97 ] ) . The data were compatible with a benefit at 2 ( OR = 0.76 [ 0.54 , 1.06 ] ) and 3 years ( OR = 0.92 [ 0.69 , 1.23 ] ) , but these findings were not statistically significant . For nonfatal reinfa rct ion , there were no significant differences between the two groups after 1 ( OR = 1.09 [ 0.76 , 1.57 ] ) , 2 ( OR = 1.10 [ 0.82 , 1.47 ] ) , or 3 years ( OR = 1.09 [ 0.88 , 1.34 ] ) of follow-up . The observed 20 % reduction in overall mortality reflects a decreased risk of cardiovascular mortality and fatal reinfa rct ion throughout at least 3 years and a reduction in sudden death during the 1st year after infa rct ion and possibly for 2 - 3 years . With respect to the independent effects of the physical exercise component of cardiac rehabilitation , the relatively small number of " exercise only " trials , combined with the possibility that they may have had a formal or informal nonexercise component precludes the possibility of reaching any definitive conclusion . To do so would require a r and omized trial of sufficient size to distinguish between no effect and the most plausible effect based on the results of this overview Background Falls are a significant public health problem . Thirty to fifty percent of the elderly of 65 years and older fall each year . Falls are the most common type of accident in this age group and can result in fractures and subsequent disabilities , increased fear of falling , social isolation , decreased mobility , and even an increased mortality . Several forms of exercise have been associated with a reduced risk of falling and with a wide range of physiological as well as psychosocial health benefits . Tai Chi Chuan seems to be the most promising form of exercise in the elderly , but the evidence is still controversial . In this article the design of a r and omized clinical trial is presented . The trial evaluates the effect of Tai Chi Chuan on fall prevention and physical and psychological function in older adults . Methods / Design 270 people of seventy years and older living at home will be identified in the files of the participating general practitioners . People will be asked to participate when meeting the following inclusion criteria : have experienced a fall in the preceding year or suffer from two of the following risk factors : disturbed balance , mobility problems , dizziness , or the use of benzodiazepines or diuretics . People will be r and omly allocated to either the Tai Chi Chuan group ( 13 weeks , twice a week ) or the no treatment control group . The primary outcome measure is the number of new falls , measured with a diary . The secondary outcome measures are balance , fear of falling , blood pressure , heart rate , lung function parameters , physical activity , functional status , quality of life , mental health , use of walking devices , medication , use of health care services , adjustments to the house , severity of fall incidents and subsequent injuries . Process parameters will be measured to evaluate the Tai Chi Chuan intervention . A cost-effectiveness analysis will be carried out alongside the evaluation of the clinical results . Follow-up measurements will be collected at 3 , 6 and 12 months after r and omization . Discussion As far as we know this is the first trial in Europe considering Tai Chi Chuan and fall prevention . This project will answer a pragmatic research question regarding the efficacy of Tai Chi Chuan regarding fall reduction Older adults with type 2 diabetes have mobility impairment and reduced fitness . This study aim ed to test the efficacy of the “ Tai Chi for Diabetes ” form , developed to address health-related problems in diabetes , including mobility and physical function . Thirty-eight older adults with stable type 2 diabetes were r and omized to Tai Chi or sham exercise , twice a week for 16 weeks . Outcomes included gait , balance , musculoskeletal and cardiovascular fitness , self-reported activity and quality of life . Static and dynamic balance index ( −5.8 ± 14.2 ; p = 0.03 ) and maximal gait speed ( 6.2 ± 11.6 % ; p = 0.005 ) improved over time , with no significant group effects . There were no changes in other measures . Non-specific effects of exercise testing and /or study participation such as outcome expectation , socialization , the Hawthorne effect , or unmeasured changes in health status or compliance with medical treatment may underlie the modest improvements in gait and balance observed in this sham-exercise-controlled trial . This Tai Chi form , although developed specifically for diabetes , may not have been of sufficient intensity , frequency , or duration to effect positive changes in many aspects of physiology or health status relevant to older people with diabetes PURPOSE To examine the effects of a 12-week tai chi program on quality of life and exercise capacity in patients with heart failure . METHODS Thirty patients with chronic stable heart failure and left ventricular ejection fraction < or = 40 % ( mean [ + /- SD ] age , 64 + /- 13 years ; mean baseline ejection fraction , 23 % + /- 7 % ; median New York Heart Association class , 2 [ range , 1 to 4 ] ) were r and omly assigned to receive usual care ( n = 15 ) , which included pharmacologic therapy and dietary and exercise counseling , or 12 weeks of tai chi training ( n = 15 ) in addition to usual care . Tai chi training consisted of a 1-hour class held twice weekly . Primary outcomes included quality of life and exercise capacity . Secondary outcomes included serum B-type natriuretic peptide and plasma catecholamine levels . For 3 control patients with missing data items at 12 weeks , previous values were carried forward . RESULTS At 12 weeks , patients in the tai chi group showed improved quality -of-life scores ( mean between-group difference in change , -25 points , P = 0.001 ) , increased distance walked in 6 minutes ( 135 meters , P = 0.001 ) , and decreased serum B-type natriuretic peptide levels ( -138 pg/mL , P = 0.03 ) compared with patients in the control group . A trend towards improvement was seen in peak oxygen uptake . No differences were detected in catecholamine levels . CONCLUSION Tai chi may be a beneficial adjunctive treatment that enhances quality of life and functional capacity in patients with chronic heart failure who are already receiving st and ard medical therapy PURPOSE This study evaluated the effect of Tai Chi Chuan ( TCC ) on the autonomic nervous modulation in older persons . METHODS Twenty TCC practitioners and 20 normal controls were included in this study . The stationary state spectral heart rate variability ( HRV ) measures between TCC practitioners and normal controls , and the sequential changes in HRV measures after classical Yang 's TCC were compared . RESULTS The total power , very low-frequency power , low-frequency power , normalized low-frequency power , and low-/high-frequency power ratios in TCC practitioners were all significantly higher than those of normal controls , whereas the heart rate and systolic and diastolic blood pressures were not different between these two groups of subjects . After TCC , the normalized high-frequency power increased significantly from 22.8 + /- 14.6 normalized units ( nu ) before TCC to 28.2 + /- 16.1 nu 30 min after TCC and to 30.6 + /- 18.4 nu 60 min after TCC . In contrast , the low-/high-frequency power ratio decreased significantly from 2.5 + /- 2.4 before TCC to 1.8 + /- 1.4 30 min after TCC and to 2.2 + /- 2.9 60 min after TCC . The heart rate , systolic blood pressure , diastolic blood pressure , mean arterial blood pressure , and pulse pressure also decreased sequentially after TCC . CONCLUSION The short-term effect of TCC was to enhance the vagal modulation and tilt the sympathovagal balance toward deceased sympathetic modulation in older persons . TCC might be good health-promoting calisthenics for older persons OBJECTIVE To estimate the incremental effects on cost and quality of life of cardiac rehabilitation after an acute coronary syndrome . DESIGN Open r and omised controlled trial with 1 year 's follow-up . Analysis was on an intention-to-treat basis . SETTING Two tertiary hospitals in Sydney . INTERVENTION 18 sessions of comprehensive exercise-based outpatient cardiac rehabilitation or conventional care as provided by the treating doctor . PARTICIPANTS 113 patients aged 41 - 75 years who were self-caring and literate in English . Patients with uncompensated heart failure , uncontrolled arrhythmias , severe and symptomatic aortic stenosis or physical impairment were excluded . MAIN OUTCOME MEASURES Costs ( hospitalisations , medication use , outpatient visits , investigations , and personal expenses ) ; and measures of quality of life . Incremental cost per quality -adjusted life year ( QALY ) saved at 1 year ( this estimate combines within- study utility effects with reported 1-year risk of survival and treatment effects of rehabilitation on mortality ) . Sensitivity analyses around a base case estimate included alternative assumptions of no treatment effect on survival , 3 years of treatment effect on survival and variations in utility . RESULTS The estimated incremental cost per QALY saved for rehabilitation relative to st and ard care was 42,535 US dollars when modelling included the reported treatment effect on survival . This increased to 70,580 US dollars per QALY saved if treatment effect on survival was not included . The results were sensitive to variations in utility and ranged from 19,685 US dollars per QALY saved to rehabilitation not being cost-effective . CONCLUSIONS The effects on quality of life tend to reinforce treatment advantages on survival for patients having postdischarge rehabilitation after an acute coronary syndrome . The estimated base case incremental cost per QALY saved is consistent with those historically accepted by decision making authorities such as the Pharmaceutical Benefits Advisory Committee In this study , 126 patients ( 90 males , average age 56 years , range 39 - 80 ) were r and omised to Wu Chian-Ch'uan style Tai Chi ( 38 ) , aerobic exercise ( 41 ) or a non-exercise support group ( 47 ) following acute myocardial infa rct ion . Patients attended twice weekly for three weeks then weekly for a further five weeks . Heart rate and blood pressure were recorded before and after each session . Over the 11 sessions of exercise there was a negative trend in diastolic blood pressure only in the Tai Chi group ( Rs = 0.79 , p < 0.01 ) . Significant trends in systolic blood pressure occurred in both exercise groups ( Rs = 0.64 and 0.63 , both p < 0.05 ) . Only four ( 8 % ) patients completed the support group eight-week programme which was less than the number completing Tai Chi ( 82 % ; p < 0.001 ) and aerobic exercise groups ( 73 % ; p < 0.001 ) BACKGROUND / AIMS Treatment for breast cancer produces side effects that diminish functional capacity and quality of life ( QOL ) among survivors . Tai Chi Chuan ( TCC ) is a moderate form of exercise that may improve functional capacity and QOL in these individuals . Women who completed treatment for breast cancer were r and omized to receive TCC or psychosocial support therapy for 12 weeks ( 60 min ; three times weekly ) . RESULTS The TCC group demonstrated significant improvements in functional capacity , including aerobic capacity , muscular strength , and flexibility , as well as QOL ; the psychosocial support therapy group showed significant improvements only in flexibility , with declines in aerobic capacity , muscular strength , and QOL . CONCLUSIONS The TCC group exhibited significant improvements in functional capacity and QOL . These data suggest that TCC may enhance functional capacity and QOL among breast cancer survivors OBJECTIVE To determine whether Tai Chi or hydrotherapy classes for individuals with chronic symptomatic hip or knee osteoarthritis ( OA ) result in measurable clinical benefits . METHODS A r and omized controlled trial was conducted among 152 older persons with chronic symptomatic hip or knee OA . Participants were r and omly allocated for 12 weeks to hydrotherapy classes ( n = 55 ) , Tai Chi classes ( n = 56 ) , or a waiting list control group ( n = 41 ) . Outcomes were assessed 12 and 24 weeks after r and omization and included pain and physical function ( Western Ontario and McMaster Universities Osteoarthritis Index ) , general health status ( Medical Outcomes Study Short Form 12 Health Survey [ SF-12 ] , version 2 ) , psychological well-being , and physical performance ( Up and Go test , 50-foot walk time , timed stair climb ) . RESULTS At 12 weeks , compared with controls , participants allocated to hydrotherapy classes demonstrated mean improvements ( 95 % confidence interval ) of 6.5 ( 0.4 , 12.7 ) and 10.5 ( 3.6 , 14.5 ) for pain and physical function scores ( range 0 - 100 ) , respectively , whereas participants allocated to Tai Chi classes demonstrated improvements of 5.2 ( -0.8 , 11.1 ) and 9.7 ( 2.8 , 16.7 ) , respectively . Both class allocations achieved significant improvements in the SF-12 physical component summary score , but only allocation to hydrotherapy achieved significant improvements in the physical performance measures . All significant improvements were sustained at 24 weeks . In this almost exclusively white sample , class attendance was higher for hydrotherapy , with 81 % attending at least half of the available 24 classes , compared with 61 % for Tai Chi . CONCLUSION Access to either hydrotherapy or Tai Chi classes can provide large and sustained improvements in physical function for many older , sedentary individuals with chronic hip or knee OA Tai chi -- moving for better balance , a falls-prevention program developed from a r and omized controlled trial for community-based use , was evaluated with the re- aim framework in 6 community centers . The program had a 100 % adoption rate and 87 % reach into the target older adult population . All centers implemented the intervention with good fidelity , and participants showed significant improvements in health-related outcome measures . This evidence -based tai chi program is practical to disseminate and can be effectively implemented and maintained in community setting |
13,527 | 18,057,267 | Evidence from the cross-sectional and longitudinal studies was inconclusive .
Evidence from r and omized controlled trials suggests that SMBG may lead to improvements in glucose control .
CONCLUSIONS SMBG may be effective in controlling blood glucose for patients with type 2 diabetes .
There is a need for studies that implement all the components of the process for self-regulation of SMBG to assess whether patient use of SMBG will improve HbA1c levels | OBJECTIVE The purpose of this systematic review was 2-fold : first , to perform a comprehensive review of relevant studies on the impact of self-monitoring of blood glucose ( SMBG ) on HbA1c levels for patients with type 2 diabetes mellitus and , second , to explore mediators and moderators within a self-regulation framework . | A cross-sectional study to assess home glucose monitoring practice s was conducted in 200 non-insulin-treated diabetic patients consecutively attending our hospital clinic . Of the 200 , 97 ( 48 % ) patients ( Group 1 ) regularly monitored urine ( n = 74 ) , blood ( n = 19 ) or both ( n = 4 ) ; 103 ( 52 % ) patients ( Group 2 ) performed no home monitoring . The two groups were similar in terms of age , sex , duration of diabetes and type of treatment . The prevalence of diabetic complications was also closely comparable and only peripheral neuropathy differed between the groups , being more common in Group 1 ( n = 12 ) than Group 2 ( n = 4 ) ; p < 0.05 . There was also no significant difference between the HbA1 concentration ( mean + /- SD ) in Group 1 ( 9.7 + /- 2.2 % ) and Group 2 ( 9.4 + /- 2.0 % ) . The mean frequency of home monitoring was four tests weekly , but only 21 ( 22 % ) kept a written record and 60 ( 62 % ) would never alter their treatment on the basis of their results . Almost a third of patients could not interpret the results of monitoring or give the normal range of values . Home glucose monitoring , particularly of urine , is widely practised in Type 2 diabetes , at considerable overall expense . However , convincing evidence of its value in helping patients improve their blood glucose control or preventing the complications of the disease is lacking OBJECTIVE To investigate the effect of meal-related self-monitoring of blood glucose on glycemic control and well-being in non-insulin-treated type 2 diabetic patients . RESEARCH DESIGN AND METHODS This 6-month study , which included 6 months of follow-up , adopted a prospect i ve , multicenter , r and omized controlled design . Subjects were r and omized to two groups : one group used a blood glucose-monitoring device , kept a blood glucose/eating diary , and received st and ardized counseling ; the control group received nonst and ardized counseling on diet and lifestyle . The primary efficacy parameter was the change in HbA(1c ) . Secondary efficacy variables included changes in body weight , lipids , and microalbumin and changes in treatment satisfaction and well-being . RESULTS In the per- protocol analysis , the use of a self-monitoring blood glucose device significantly reduced HbA(1c ) levels by 1.0 + /- 1.08 % compared with 0.54 + /- 1.41 % for the control group ( P = 0.0086 ) ; subgroup analysis showed three types of responders . Body weight , total cholesterol , and microalbumin improved when using a glucometer , but there was no statistically significant difference between the two groups . Treatment satisfaction increased in both groups to a similar extent ( P = 0.9 ) . Self-monitoring result ed in a marked improvement of general well-being with significant improvements in the subitems depression ( P = 0.032 ) and lack of well-being ( P = 0.02 ) . CONCLUSIONS Meal-related self-monitoring of blood glucose within a structured counseling program improved glycemic control in the majority of non-insulin-treated type 2 diabetic patients in this study . The finding of three types of responders will be important for future planning of counseling and educational interventions Some features of diabetes care and diabetes treatment regimen which may have an impact on health-related quality of life ( HRQOL ) in people with diabetes were studied cross-sectionally using the SF-20 question naire . Of the 381 subjects with Type 2 diabetes aged under 65 years , 260 ( 68 % ) participated in the study . On univariate analysis , HRQOL was associated with regular clinical review ( check-up at least twice a year ) and continuity of care ( the same GP for at least 2 years ) , education by a diabetes nurse , and satisfaction with diabetes education . No associations were found between the HRQOL dimensions and home glucose monitoring , participation in educational courses , or satisfaction with care . On logistic regression analysis only good continuity of care was significantly associated with the better well-being dimensions of the SF 20 ( ORs 2.5 - 6.0 ) . However , good continuity of care was also associated with less satisfactory glucose control ( HbA(1c ) 8.9 + /- 2.0 ( + /- SD ) vs 8.3 + /- 2.0 % , P=0.04 ) . It is concluded that a permanent physician-patient relationship may improve HRQOL in subjects with Type 2 diabetes , but further prospect i ve studies are needed to confirm this finding Objective To determine whether self monitoring , alone or with instruction in incorporating the results into self care , is more effective than usual care in improving glycaemic control in non-insulin treated patients with type 2 diabetes . Design Three arm , open , parallel group r and omised trial . Setting 48 general practice s in Oxfordshire and South Yorkshire . Participants 453 patients with non-insulin treated type 2 diabetes ( mean age 65.7 years ) for a median duration of three years and a mean haemoglobin A1c level of 7.5 % . Interventions St and ardised usual care with measurements of HbA1c every three months as the control group ( n=152 ) , blood glucose self monitoring with advice for patients to contact their doctor for interpretation of results , in addition to usual care ( n=150 ) , and blood glucose self monitoring with additional training of patients in interpretation and application of the results to enhance motivation and maintain adherence to a healthy lifestyle ( n=151 ) . Main outcome measure HbA1c level measured at 12 months . Results At 12 months the differences in HbA1c level between the three groups ( adjusted for baseline HbA1c level ) were not statistically significant ( P=0.12 ) . The difference in unadjusted mean change in HbA1c level from baseline to 12 months between the control and less intensive self monitoring groups was −0.14 % ( 95 % confidence interval −0.35 % to 0.07 % ) and between the control and more intensive self monitoring groups was −0.17 % ( −0.37 % to 0.03 % ) . Conclusions Evidence is not convincing of an effect of self monitoring blood glucose , with or without instruction in incorporating findings into self care , in improving glycaemic control compared with usual care in reasonably well controlled non-insulin treated patients with type 2 diabetes . Trial registration Current Controlled Trials IS RCT N47464659 The goal of this study was to compare the relative efficacy and cost of self-monitoring of blood glucose ( SMBG ) with routine urine testing in the management of patients with type II ( non-insulin-dependent ) diabetes mellitus not treated with insulin . Fifty-four patients with type II diabetes mellitus , not treated with insulin , who had inadequate glucose control on diet aloneor diet and oral hypoglycemic agents were studied . Patients performed SMBG or urine glucose testing as part of a st and ardized treatment program that also included diet and exercise counseling . During the 6-mo study , both the urine-testing and SMBG groups showed similar improvement in glycemic control ; within each group , there were significant improvements in fasting plasma glucose ( reduction of 1.4 ± 3.2 mM , P < 0.03 ) and glycosylated hemoglobin ( reduction of 2.0 ± 3.4 % , P < 0.01 ) levels . Seventeen ( 31 % ) of54 patients actually normalized their glycosylated hemoglobin values , 9 in the urine-testing group and 8 in the SMBG group . Comparisons between the urine-testing and SMBG groups showed no significant differences in mean fasting plasma glucose ( P > 0.86 ) , glycosylated hemoglobin ( P > 0.95 ) , or weight ( P < 0.19 ) . In patients with type II diabetes mellitus not treated with insulin , SMBG is no more effective , but is 8–12 times more expensive , thanurine testing in facilitating improved glycemic control . Our results do not support widespread use of SMBG in diabetic patients not treated with insulin Background We do not yet know how to use blood glucose self-monitoring ( BGSM ) most effectively in the self-management of type 2 diabetes treated with oral medication . Training in monitoring may be most effective in improving glycaemic control and well being when results are linked to behavioural change . Methods / design DiGEM is a three arm r and omised parallel group trial set in UK general practice s. A total of 450 patients with type 2 diabetes managed with lifestyle or oral glucose lowering medication are included . The trial compares effectiveness of three strategies for monitoring glycaemic control over 12 months ( 1 ) a control group with three monthly HbA1c measurements ; interpreted with nurse-practitioner ; ( 2 ) A self-testing of blood glucose group ; interpreted with nurse- practitioner to inform adjustment of medication in addition to 1 ; ( 3 ) A self-monitoring of blood glucose group with personal use of results to interpret results in relation to lifestyle changes in addition to 1 and 2.The trial has an 80 % power at a 5 % level of significance to detect a difference in change in the primary outcome , HbA1c of 0.5 % between groups , allowing for an attrition rate of 10 % . Secondary outcome measures include health service costs , well-being , and the intervention effect in sub-groups defined by duration of diabetes , current management , health status at baseline and co-morbidity . A mediation analysis will explore the extent to which changes in beliefs about self-management of diabetes between experimental groups leads to changes in outcomes in accordance with the Common Sense Model of illness . The study is open and has recruited more than half the target sample . The trial is expected to report in 2007 . Discussion The DiGEM intervention and trial design address weaknesses of previous research by use of a sample size with power to detect a clinical ly significant change in HbA1c , recruitment from a well-characterised primary care population , definition of feasible monitoring and behaviour change strategies based on psychological theory and evidence , and measures along the hypothesised causal path from cognitions to behaviours and disease and well being related outcomes . The trial will provide evidence to support , focus or discourage use of specific BGSM strategies A diabetes protocol characterized by self-monitoring of blood glucose was introduced in four general practice s with the aim of making the frequency of consultations dependent on the metabolic regulation and emphasizing body weight reduction . The feasibility of the programme was investigated and the results after 1 year were compared with those of conventional care in four control practice s. In the experimental practice s , 13 patients switched from a medical specialist 's to a general practitioner 's supervision , 20 remained under supervision of their GP and 33 started self-monitoring . The self-monitoring rate , the consultation frequency according to protocol , the low number of dropouts and inadequate referrals and adherence to the therapeutic scheme showed that the protocol was feasible for both the GPs and the patients . At the initial assessment , the regulation of the diabetes was worse in patients of the experimental group , compared with those of the control group ( mean HbA1 9.7 % vs 8.9 % ; p less than 0.05 ) . On average , patients in the experimental group ( n = 56 ) lost 0.4 kg of body weight , whereas those in the control group ( n = 73 ) gained 0.1 kg ( n.s . ) . The mean change in HbA1 , adjusted for the initial value , was -0.4 % in the experimental and + 0.5 % in the control group ( p less than 0.05 ) . The results of the protocol can be attributed to a combination of greater participation of the patient , the individualized consultation frequency and the prescription of oral hypoglycaemic agents according to body weight development OBJECTIVE Recent Veterans Affairs ( VA ) guidelines recommend that persons with stable type 2 diabetes controlled on oral agents or diet therapy perform self-monitoring of blood glucose ( SMBG ) twice weekly . We assessed the impact of a modification of these guidelines on hemoglobin A1c ( HbA1c ) and monitoring cost . STUDY DESIGN Retrospective , noncrossover clinical trial . PATIENTS AND METHODS We instructed persons with type 2 diabetes to perform SMBG testing according to modified adapted VA guidelines . We compared patients ' baseline average testing frequency and HbA1c with those obtained during a 6-month interval beginning 2 months after implementation of the modified guidelines . The impact on the cost of monitoring was calculated . RESULTS At baseline , 913 of 1,213 SMBG users with diabetes on oral hypoglycemic agents had HbA1c tested ( HbA1c = 7.83 % + /- 1.34 % ) ; their frequency of SMBG was 1.36 + /- 0.95 strips per patient per day . Postimplementation , 974 of 1,278 persons with diabetes had HbA1c tested ( HbA1c = 7.86 % + /- 1.54 % ; P= .63 vs baseline ) ; frequency of SMBG decreased by 46 % to 0.74 + /- 0.50 strips per patient per day ( P < .0001 ) . At baseline , 154 of 254 SMBG users with diabetes on diet therapy had HbA1c tested ( HbA1c = 6.85 % + /- 0.97 % ) ; their frequency of SMBG was 1.07 + /- 0.90 strips per patient per day . Postimplementation , 177 of 282 diet-treated persons with diabetes had HbA1c tested ( HbA1c = 6.78 % + /- 1.20 % ; P = .56 vs baseline ) ; frequency of SMBG decreased by 35 % to 0.70 + /- 0.51 strips per patient per day ( P < .0001 ) . Similar findings were observed in a cohort of 421 drug-treated patients with paired HbA1c data before and after implementation , and a cohort of 50 diet-treated patients with paired HbA1c data . Linear regression analysis showed no significant impact on individuals ' HbA1c with reduction in strip use . Average monthly cost savings were $ 8,800 , or $ 6.37 per patient per month . CONCLUSIONS This program decreased the frequency of SMBG in persons with type 2 diabetes , result ing in substantial cost savings without affecting glucose control OBJECTIVE The Internet is used worldwide as a communication tool . To improve the quality of diabetes control , we investigated the effectiveness of an Internet-based blood glucose monitoring system ( IBGMS ) on controlling the changes in HbA(1c ) levels . RESEARCH DESIGN AND METHODS We conducted a r and omized clinical trial involving 110 patients who visited the outpatient clinic at the Kangnam St. Mary 's Hospital for 3 months . The study subjects were treated with IBGMS for 12 weeks , and the control group received the usual outpatient management over the same period . HbA(1c ) and other laboratory tests were performed twice , once at the beginning of the study and again at the end of the study . RESULTS The test results from the beginning of the study established that there were no significant differences between the two groups with respect to age , sex , diabetes duration , BMI , blood pressure , HbA(1c ) , and other laboratory data . On follow-up examination 12 weeks later , HbA(1c ) levels were significantly decreased from 7.59 to 6.94 % within the intervention group ( P < 0.001 ) . At the end of the study , HbA(1c ) levels in the intervention group were significantly lower than in the control group after adjusting the baseline HbA(1c ) ( 6.94 vs. 7.62 % ; P < 0.001 , respectively ) . Among patients with baseline HbA(1c ) < 7.0 % , the patients in the intervention group had lower HbA(1c ) than those in the control group ( 6.38 vs. 6.99 % ; P < 0.05 ) . Among the patients with a baseline HbA(1c ) > or = 7.0 % , the difference between the two groups appeared more obvious : HbA(1c ) levels at the end of the study were 8.12 % . CONCLUSIONS This new IBGMS result ed in a significant reduction of HbA(1c ) during the study period . We propose that this IBGMS be used as a method for improving diabetes control The Stockholm Diabetes Intervention Study ( SDIS ) showed that lower blood glucose levels led to halted or retarded microvascular complications in patients with insulin-dependent ( type 1 ) diabetes mellitus ( IDDM ) . Modern education was combined with tutoring , which led to improved blood glucose control in a r and omized group of patients . In this setting , the expert-physician met and expert-patient in a mutual effort to make the patient able to live his daily life according to the wishes he had , without too much special consideration to the diabetes . The goals of the treatment were thus to improve the daily quality of life of the patient while keeping the HbA1c sufficiently low to avoid severe complications . The physician has to accept a new role as a teacher and tutor , and as such a caring but still professional friend BACKGROUND Frequent blood glucose ( BG ) monitoring is a critical component of diabetes management , yet many barriers exist to consistent monitoring . METHODS In this r and omized controlled trial , we sought to determine if an educational manual , the Blood Sugar Monitoring Owner 's Manual ( BGMOM ) , could increase adherence to BG monitoring by helping patients form realistic expectations and responses to BG monitoring results . The 199 participants were recruited from a multidisciplinary diabetes clinic and had high-risk diabetes ( hemoglobin A(1C ) > or=8.0 % ) ; 35 % had type 1 diabetes mellitus . Participants were r and omized to 1 of 3 groups : BGMOM intervention ( BGM+ ) , attention control ( BG meter only [ MT ] ) , or st and ard care ( SC ) . The BGM+ and MT groups received BG meters and meter education ; the BGM+ group also received BGMOM booklets . The SC group received usual care . Data gathered during 6 months of follow-up included BG monitoring frequency and hemoglobin A(1C ) measurement . RESULTS Monitoring frequency increased significantly in the BGM+ group ( 1.9 + /- 1.3 to 2.8 + /- 1.5 times daily , P<.001 ) but only slightly in the MT group ( 1.7 + /- 1.3 to 2.0 + /- 1.3 times daily ) . The BGM+ group experienced the greatest improvement in hemoglobin A(1C ) level ( BGM+ : -0.13 + /- 1.28 ; MT : -0.04 + /- 1.31 ; SC : 0.04 + /- 1.10 ) . Further , a higher percentage of those in the BGM+ group ( 61 % ) improved their glycemic control compared with the other groups ( 44 % ; P = .05 ) . Finally , the BGM+ group displayed the most knowledge about the definition of hemoglobin A(1C ) ( P = .04 ) and reported the least amount of negative affect about out-of-range BG monitoring results ( P = .03 ) . CONCLUSION As an adjunct to st and ard diabetes education and support , a manual such as the BGMOM can help optimize BG monitoring and glycemic control Self-monitoring of blood glucose ( SBGM ) is widely recommended for both type 1 and type 2 diabetic patients despite the lack of evidence of benefit in glucose control or as an aid in weight loss in type 2 subjects . This study tested the hypothesis that combined use of SMBG and dietary carbohydrate ( CHO ) counting , using the blood monitoring results to shape dietary CHO quotas , is beneficial in managing type 2 diabetes . Twenty-three over-weight ( body mass index , BMI 27.5–44 kg/m2 ) patients aged 40–75 participated in a 28-week behavioral weight control program . Baseline hemoglobin HbA 1c ranged between 9.5 % and 13.5 % ( normal range 5.5%–7.7 % ) . Subjects were matched for weight , sex , and HbAlc and assigned to small ( 4–8 participants ) groups which met weekly for 12 weeks and then monthly for 16 weeks . After 8 weeks , the group were r and omized either to continue the behavioral program or to have SMBG and dietary CHO counting . Glucose monitoring was performed 6 times daily ( pre- and 2h postpr and ially ) for the first month , focusing on the meal increment and correlating this to dietary CHO intake . Weight loss was identical in both groups during the year of follow-up . The HbA1c level showed a progressive decline in experimental subjects ( P<0.05 ) , whereas there was no improvement in control subjects Objectives To evaluate whether a course teaching flexible intensive insulin treatment combining dietary freedom and insulin adjustment can improve both glycaemic control and quality of life in type 1 diabetes . Design R and omised design with participants either attending training immediately ( immediate DAFNE ) or acting as waiting list controls and attending “ delayed DAFNE ” training 6 months later . Setting Secondary care diabetes clinics in three English health districts . Participants 169 adults with type 1 diabetes and moderate or poor glycaemic control . Main outcome measures Glycated haemoglobin ( HbA1c ) , severe hypoglycaemia , impact of diabetes on quality of life ( ADDQoL ) . Results At 6 months , HbA1c was significantly better in immediate DAFNE patients ( mean 8.4 % ) than in delayed DAFNE patients ( 9.4 % ) ( t=6.1 , P < 0.0001 ) . The impact of diabetes on dietary freedom was significantly improved in immediate DAFNE patients compared with delayed DAFNE patients ( t= − 5.4 , P < 0.0001 ) , as was the impact of diabetes on overall quality of life ( t=2.9 , P < 0.01 ) . General wellbeing and treatment satisfaction were also significantly improved , but severe hypoglycaemia , weight , and lipids remained unchanged . Improvements in “ present quality of life ” did not reach significance at 6 months but were significant by 1 year . Conclusion Skills training promoting dietary freedom improved quality of life and glycaemic control in people with type 1 diabetes without worsening severe hypoglycaemia or cardiovascular risk . This approach has the potential to enable more people to adopt intensive insulin treatment and is worthy of further investigation PURPOSE The relationship between the self-monitoring of blood glucose ( SMBG ) and glycemic control in patients with type 2 diabetes mellitus in a Veterans Affairs ( VA ) medical center was studied . METHODS Laboratory , inpatient , outpatient , and demographic data for patients with type 2 diabetes mellitus who were seen for three years continuously or receiving their care regularly from a single Texas VA facility between October 1 , 1999 , and September 30 , 2002 , were obtained . Local pharmacy data were used to identify patients who received blood-glucosemonitoring strips . Patients were assigned to one of four mutually exclusive groups : those who did not receive monitoring strips at all , those who received strips in fiscal year ( FY ) 2002 only , those who received strips in FYs 2001 and 2002 , and those who received strips during all three years ( FYs 2000 , 2001 , and 2002 ) . Frequency of monitoring and case-mix scores were measured . Nonparametric statistics were used to compare the demographic and clinical characteristics of the four groups . Robust regression was used to analyze the relationships between SMBG and glycemic control in FY 2002 . RESULTS Of the 1185 patients who received oral hypoglycemic medications during all three fiscal years , 976 patients met the criteria for inclusion in one of the four groups . There were no significant differences among the four groups in baseline hemoglobin A1c ( HbA1c ) values , body mass index , or case-mix scores . The Kruskal-Wallis test found no significant difference among the four groups in the number of laboratory blood glucose tests conducted , but there were significant differences in the number of HbA1c tests conducted among the groups . CONCLUSION SMBG was not associated with glycemic control in VA patients with type 2 diabetes mellitus managed on oral hypoglycemic medications The purpose of the study was to determine whether blood glucose monitoring strips influence the management of patients with non-insulin dependent diabetes ( NIDDM ) in the primary care setting . The medical records of 115 patients with NIDDM taking a sulfonylurea drug ( oral hypoglycemic agent ) during the review period were r and omly selected for review . Patients were divided into two groups : those who did not receive a prescription for blood glucose monitoring strips during 1995 and 1996 and those who did for the same 2 years . The main outcome measures were hemoglobin A1c , blood sugar , number of laboratory tests ordered , and number and type of treatment interventions . No statistically significant differences between groups were noted for any measured parameter . Glucose control was independent of number of strips dispensed . Home glucose monitoring strips did not affect the management of patients with NIDDM taking a sulfonylurea agent in the primary care setting |
13,528 | 23,303,434 | RESULTS This review found ample and moderately consistent evidence that adverse mental health and alcohol consumption are associated with reduced adherence .
This review suggests that psychosocial factors , namely , depression and alcohol may have adverse effects upon HIV-related outcomes . | OBJECTIVES To conduct a systematic review of the literature to examine the interrelationship between mental health and treatment outcomes in low-income and middle-income setting s ; to up date the work of Collins et al. ( 2006 ) . | AIMS AND OBJECTIVES This study aim ed to examine the effects of nurse-delivered home visits combined with telephone intervention on medication adherence , and quality of life in HIV-infected heroin users . BACKGROUND Drug use is consistently reported as a risk factor for medication non-adherence in HIV-infected people . DESIGN An experimental , pretests and post-tests , design was used : baseline and at eight months . METHODS A sample of 116 participants was recruited from three antiretroviral treatment sites , and 98 participants completed the study . They were r and omly assigned to two groups : 58 in the experimental group and 58 in the control group . The experimental group received nurse-delivered home visits combined with telephone intervention over eight months , while the control group only received routine care . The question naire of Community Programs for Clinical Research on AIDS ( CPCRA ) Antiretroviral Medication Self-Report was used to assess levels of adherence , while quality of life and depression were evaluated using Chinese versions of World Health Organization Quality of Life Instrument-Abbreviated version ( WHOQOL-BREF ) and Self-rating Depression Scale , respectively . Data were obtained at baseline and eight months . RESULTS At the end of eight months , participants in the experimental group were more likely to report taking 100 % of pills ( Fisher 's exact = 14.3 , p = 0.0001 ) and taking pills on time ( Fisher 's exact = 18.64 , p = 0.0001 ) than those in the control group . There were significant effects of intervention in physical ( F = 10.47 , p = 0.002 ) , psychological ( F = 9.41 , p = 0.003 ) , social ( F = 4.09 , p = 0.046 ) and environmental ( F = 4.80 , p = 0.031 ) domains of WHOQOL and depression ( F = 5.58 , p = 0.02 ) . CONCLUSIONS Home visits and telephone calls are effective in promoting adherence to antiretroviral treatment and in improving the participants ' quality of life and depressive symptoms in HIV-infected heroin users . RELEVANCE TO CLINICAL PRACTICE It is important for nurses to recognise the issues of non-adherence to antiretroviral treatment in heroin users . Besides st and ard care , nurses should consider conducting home visits and telephone calls to ensure better health outcome of antiretroviral treatment in this population Abstract A r and om sample of 271 people living with HIV ( PLWH ) who were former plasma/blood donors and a convenience sample of 67 HIV negative villagers were anonymously interviewed . Compared with the non-PLWH , PLWH reported higher prevalence of symptoms of depression ( adjusted OR = 2.53 , p=0.001 ) , anxiety ( adjusted OR = 1.85 , p=0.04 ) , and stress ( adjusted OR = 1.77 , p=0.06 ) . Of the PLWH respondents , 81.7 % received Highly Active Antiretroviral Therapy ( HAART ) ; 32.1 % of whom reported some side effects . Respectively 13.7 % , 37.4 % , and 38.4 % PLWH perceived discrimination from their family members , relatives/friends , and neighbors . Absence of HAART , poor physical function , perceived discrimination from relatives and friends , and low level of resilience were associated with depression ( stepwise regression ; β = − 0.28–0.17 , R-square = 0.22 ) , anxiety and stress ( R-square = 0.32 and 0.16 , respectively ) . The majority of respondents ( 70.1 % ) desired group intervention as a means for providing psychological support services . Relevant programs should both remove risk factors ( e.g. , absence of medical treatment , HIV-related discrimination ) and promote protective factors ( e.g. , resilience ) . Support group is one of the potentially useful approaches to provide psychological support services Two-thirds of those with HIV worldwide live in sub-Saharan Africa . Alcohol use is associated with the HIV epidemic through risky sex and suboptimal ARV adherence . In western Kenya , hazardous drinking was reported by HIV ( 53 % ) and general medicine ( 68 % ) out patients . Cognitive behavioral treatment ( CBT ) has demonstrated strong efficacy to reduce alcohol use . This article reports on a systematic cultural adaptation and pilot feasibility study of group paraprofessional-delivered CBT to reduce alcohol use among HIV-infected out patients in Eldoret , Kenya . Following adaptation and counselor training , five pilot groups were run ( n = 27 ) . Overall attendance was 77 % . Percent days abstinent from alcohol ( PDA ) before session 1 was 52–100 % ( women ) and 21–36 % ( men ) , and by session 6 was 96–100 % ( women ) and 89–100 % ( men ) . PDA effect sizes ( Cohen ’s d ) between first and last CBT session were 2.32 ( women ) and 2.64 ( men ) . Participants reported treatment satisfaction . Results indicate feasibility , acceptability and preliminary efficacy for CBT in Kenya BACKGROUND Psychiatric disorders in HIV/AIDS are common , emerging soon after diagnosis or during the subsequent course of illness . However , there are few prospect i ve studies on the rates of psychiatric disorders in HIV/AIDS , particularly in the context of the developing world . METHODS Sixty-five patients with recently diagnosed HIV were interviewed on presentation to a hospital-based HIV clinic and then 6 months later . On both interviews , the patients were assessed using the MINI International Neuropsychiatric Interview , the Carver Brief COPE , and the Sheehan Disability Scale . Exposure to negative life events and risk behaviors was also evaluated . RESULTS The overall prevalence of psychiatric disorders in the follow-up period remained high ( 56 % of patients had at least one psychiatric disorder at baseline , and 48 % of patients had at least one psychiatric disorder at 6 months ) . Depression and posttraumatic stress disorder ( PTSD ) were the most prevalent disorders at both baseline ( 34.9 % and 14.8 % ) and follow-up ( 26 % and 20 % ) , respectively . More than half of all patients with depression at baseline improved ( 16 of 29 ; 55.1 % ) . However , there was a new onset of both depression ( 4 of 49 ; 8.1 % ) and PTSD ( 12 of 17 ; 70.5 % ) on follow-up . In univariate analysis , depression on follow-up was significantly associated with : ( a ) disability in work/social/family functioning , ( b ) greater number of negative life events , and ( c ) a decline in CD4 lymphocyte count . Univariate analysis also revealed that a diagnosis of PTSD on follow-up was significantly associated with ( a ) a longer duration of infection and ( b ) baseline disability in work/social/family functioning . However , in multivariate analysis , only disability scores predicted the diagnoses of major depression and PTSD on follow-up assessment . Persistence of risky sexual behaviour was also noted , with a significantly higher number of participants reporting nonuse of condom on follow-up . There appeared to be a shift from maladaptive coping behaviors to more adaptive coping behaviors over the 6-month period . CONCLUSION The rate of psychiatric disorders in HIV/AIDS patients was consistent over time . These findings emphasize the importance of regular evaluation for psychiatric disorders in HIV/AIDS patients , not only at the commencement of treatment but also during subsequent follow-up visits Background The devastating impact of AIDS in the world especially in sub-Saharan Africa has led to an unprecedented global effort to ensure access to antiretroviral ( ARV ) drugs . Given that medication-taking behavior can immensely affect an individual 's response ; ART adherence is now widely recognized as an ' Achilles heel ' for the successful outcome . The present study was undertaken to investigate the rate and predictors of adherence to antiretroviral therapy among HIV-infected persons in southwest Ethiopia . Methods The study was conducted in the antiretroviral therapy unit of Jimma University Specialized Hospital . A prospect i ve study was undertaken on a total of 400 HIV infected person . Data were collected using a pre-tested interviewer-administered structured question naire at first month ( M0 ) and third month ( M3 ) follow up visits . Results A total of 400 and 383 patients at baseline ( M0 ) and at follow up visit ( M3 ) respectively were interviewed . Self-reported dose adherence in the study area was 94.3 % . The rate considering the combined indicator ( dose , time and food ) was 75.7 % . Within a three month follow up period , dose adherence decreased by 2 % and overall adherence rate decreased by more than 3 % . Adherence was common in those patients who have a social support ( OR , 1.82 , 95%CI , 1.04 , 3.21 ) . Patients who were not depressed were two times more likely to be adherent than those who were depressed ( OR , 2.13 , 95%CI , 1.18 , 3.81 ) . However , at the follow up visit , social support ( OR , 2.42 , 95%CI , 1.29 , 4.55 ) and the use of memory aids ( OR , 3.29 , 95%CI , 1.44 , 7.51 ) were found to be independent predictors of adherence . The principal reasons reported for skipping doses in this study were simply forgetting , feeling sick or ill , being busy and running out of medication in more than 75 % of the cases . Conclusion The self reported adherence rate was high in the study area . The study showed that adherence is a dynamic process which changes overtime and can not reliably be predicted by a few patient characteristics that are assumed to vary with time . Adherence is a process , not a single event , and adherence support should be integrated into regular clinical follow up Objective : To examine the effect of a 15-session individually delivered cognitive behavioral intervention on antiretroviral ( ART ) medication adherence . Design : A multisite , 2-group , r and omized controlled trial . Participants : Two hundred four HIV-infected participants with self-reported ART adherence < 85 % from a total of 3818 participants screened were r and omized into the trial . Potential participants were recruited for the main trial based on sexual risk criteria in Los Angeles , Milwaukee , New York , and San Francisco . Intervention : The primary outcome of the intervention was a reduction in HIV transmission risk behaviors . Fifteen 90-minute individually delivered sessions were divided into 3 modules : Stress , Coping , and Adjustment ; Safer Behaviors ; and Health Behaviors , including an emphasis on ART adherence . Controls received no intervention until trial completion . Both groups completed follow-up assessment s at 5 , 10 , 15 , 20 , and 25 months after r and omization . Main Outcome Measure : Self-reported ART adherence as measured by 3-day computerized assessment . Results : A significance difference in rates of reported adherence was observed between intervention and control participants at months 5 and 15 , corresponding to the assessment s after the Stress , Coping , and Adjustment module ( 5-month time point ) and after the Health Behaviors module ( 15-month time point ) . The relative improvements among the intervention group compared with the control group dissipated at follow-up . Conclusions : Cognitive behavioral intervention programs may effectively improve ART adherence , but the effects of intervention may be short-lived The effects of alcohol abuse on HIV disease progression have not been definitively established . A prospect i ve , 30-month , longitudinal study of 231 HIV(+ ) adults included history of alcohol and illicit drug use , adherence to antiretroviral therapy ( ART ) , CD4(+ ) cell count , and HIV viral load every 6 months . Frequent alcohol users ( two or more drinks daily ) were 2.91 times ( 95 % CI : 1.23 - 6.85 , p = 0.015 ) more likely to present a decline of CD4 to < or=200 cells/microl , independent of baseline CD4(+ ) cell count and HIV viral load , antiretroviral use over time , time since HIV diagnosis , age , and gender . Frequent alcohol users who were not on ART also increased their risk for CD4 cell decline to < or=200 cells/mm(3 ) ( HR = 7.76 : 95 % CI : 1.2 - 49.2 , p = 0.03 ) . Combined frequent alcohol use with crack-cocaine showed a significant risk of CD4(+ ) cell decline ( HR = 3.57 : 95 % CI : 1.24 - 10.31 , p = 0.018 ) . Frequent alcohol intake was associated with higher viral load over time ( beta = 0.259 , p = 0.038 ) . This significance was maintained in those receiving ART ( beta = 0.384 , p = 0.0457 ) , but not in those without ART . Frequent alcohol intake and the combination of frequent alcohol and crack-cocaine accelerate HIV disease progression . The effect of alcohol on CD4(+ ) cell decline appears to be independent of ART , through a direct action on CD4 cells , although alcohol and substance abuse may lead to unmeasured behaviors that promote HIV disease progression . The effect of alcohol abuse on viral load , however , appears to be through reduced adherence to ART Objective : To test the utility of the necessity-concerns framework in predicting highly active antiretroviral therapy ( HAART ) uptake and adherence . Methods : This was a prospect i ve follow-up study . Consecutive patients who were not currently receiving HAART were referred by their HIV physician . Immediately after a recommendation of HAART , patients completed the Beliefs about Medicines Question naire assessing their perceptions of personal necessity for HAART and concerns about potential adverse effects . The influence of these beliefs on the decision to accept or decline HAART and adherence 12 months later were assessed . Results : One hundred fifty-three participants were given a recommendation of HAART , and 136 ( 88.9 % ) returned completed question naires . Thirty-eight participants ( 28 % ) initially rejected the treatment offer . Uptake of HAART was associated with perceptions of personal necessity for treatment ( odds ratio [ OR ] = 7.41 , 95 % confidence interval [ CI ] : 2.84 to 19.37 ) and concerns about potential adverse effects ( OR = 0.19 , 95 % CI : 0.07 to 0.48 ) . There was a significant decline in adherence over time . Perceived necessity ( OR = 2.19 , 95 % CI : 1.02 to 4.71 ) and concerns about adverse effects ( OR = 0.45 , 95 % CI : 0.22 to 0.96 ) , elicited before initiating HAART , predicted subsequent adherence . These associations were independent of clinical variables and depression . Conclusions : The necessity-concerns framework is a useful theoretic model for underst and ing patient perspectives of HAART and predicting uptake and adherence , with implication s for the design of evidence -based interventions Alcohol use and depressive symptoms are associated with reduced access to antiretroviral therapy ( ART ) in the developed world . Whether alcohol use and depressive symptoms limit access to ART in re source -limited setting s is unknown . This cross-sectional study examined the association between alcohol use , depressive symptoms and the receipt of ART among r and omly selected HIV-positive persons presenting for primary health care services at an outpatient HIV clinic in Ug and a. Depressive symptoms were defined by the Hopkins Symptom Checklist and alcohol use was measured through frequency of consumption questions . Antiretroviral use was assessed using a st and ardized survey and confirmed by medical record review . Predictors of ART use were determined via logistic regression . Among 421 HIV-infected patients , factors associated with the receipt of ART were having at least primary education , having an opportunistic infection in the last 3 months , and not drinking within the last year OBJECTIVE To evaluate cognitive-behavioral therapy to enhance medication adherence and reduce depression ( CBT-AD ) in individuals with HIV . DESIGN A two arm , r and omized , controlled , cross-over trial comparing CBT-AD to enhanced treatment as usual only ( ETAU ) . ETAU , which both groups received , included a single-session intervention for adherence and a letter to the patient 's provider documenting her or his continued depression . The intervention group also received 10 to 12 sessions of CBT-AD . MAIN OUTCOME MEASURES Adherence to antiretroviral therapy as assessed by Medication Event Monitoring Systems ( MEMs ) and depression as assessed by blinded structured evaluation . RESULTS At the acute outcome assessment ( 3-months ) , those who received CBT-AD evidence d significantly greater improvements in medication adherence and depression relative to the comparison group . Those who were originally assigned to the comparison group who chose to cross over to CBT-AD showed similar improvements in both depression and adherence outcomes . Treatment gains for those in the intervention group were generally maintained at 6- and 12-month follow-up assessment s. By the end of the follow-up period , those originally assigned CBT-AD demonstrated improvements in plasma HIV RNA concentrations , though these differences did not emerge before the cross-over , and hence there were not between-groups differences . CONCLUSIONS CBT-AD is a potentially efficacious approach for individuals with HIV struggling with depression and adherence . Replication and extension in larger efficacy trials are needed Background : In the era of antiretroviral therapy ( ART ) , depression and substance use predict hastened HIV disease progression , but the underlying biological or behavioral mechanisms that explain these effects are not fully understood . Methods : Using outcome data from 603 participants enrolled in a r and omized controlled trial of a behavioral intervention , binary logistic and linear regression were employed to examine whether inconsistent patterns of ART utilization partially mediated the effects of depression and substance use on higher HIV viral load over a 25-month follow-up . Results : Elevated affective symptoms of depression independently predicted ART discontinuation [ adjusted odds ratio = 1.39 , 95 % confidence interval ( CI ) = 1.08 to 1.78 ] , and use of stimulants at least weekly independently predicted intermittent ART utilization ( adjusted odds ratio = 2.62 , 95 % CI = 1.45 to 4.73 ) . After controlling for the average self-reported percentage of ART doses taken and baseline T-helper ( CD4 + ) count , elevated depressive symptoms predicted a 50 % higher mean viral load , and weekly stimulant use predicted a 137 % higher mean viral load . These effects became nonsignificant after accounting for inconsistent patterns of ART utilization , providing evidence of partial mediation . Conclusions : Inconsistent patterns of ART utilization may partially explain the effects of depression and stimulant use on hastened HIV disease progression Abstract We examined trends and predictors of quality of life ( QOL ) over 12 months among a prospect i ve cohort of 947 HIV-1-infected adults initiating highly active antiretroviral therapy ( HAART ) between May 2003 and May 2004 in rural Ug and a. Participants provided clinical , demographic and psychosocial data at baseline and every three months thereafter . Outcome measures included physical and mental health summary scores based on the Medical Outcomes Study -HIV Health Survey ( MOS-HIV ) . Generalised estimating equations were used to assess magnitude of change in summary scores and factors associated with QOL . Of 710 women and 237 men enroled , the mean age was 38.7 years and mean baseline CD4 cell count was 124.1 cells/µL. At enrolment , physical and mental health summary scores were 39.2 and 40 , respectively . By 12 months of HAART , scores increased by 11.2 points ( p < 0.001 ) and 7.4 points ( p < 0.001 ) , respectively . For both scores , most gains were achieved by the third month of therapy . While several clinical , psychosocial and sociodemographic factors predicted QOL at HAART initiation , financial dependence on others was the only remaining predictor after controlling for time on HAART . Interventions to enhance the economic and employment opportunities of patients taking HAART in rural Africa may help maximise gains in QOL CONTEXT The impact of depression on morbidity and mortality among women with human immunodeficiency virus ( HIV ) has not been examined despite the fact that women with HIV have substantially higher rates of depression than their male counterparts . OBJECTIVE To determine the association of depressive symptoms with HIV-related mortality and decline in CD4 lymphocyte counts among women with HIV . DESIGN The HIV Epidemiologic Research Study , a prospect i ve , longitudinal cohort study conducted from April 1993 through January 1995 , with follow-up through March 2000 . SETTING Four academic medical centers in Baltimore , Md ; Bronx , NY ; Providence , RI ; and Detroit , Mich. PARTICIPANTS A total of 765 HIV-seropositive women aged 16 to 55 years . MAIN OUTCOME MEASURES HIV-related mortality and CD4 cell count slope decline over a maximum of 7 years , compared among women with limited or no depressive symptoms , intermittent depressive symptoms , or chronic depressive symptoms , as measured using the self-report Center for Epidemiologic Studies Depression Scale . RESULTS In multivariate analyses controlling for clinical , treatment , and other factors , women with chronic depressive symptoms were 2 times more likely to die than women with limited or no depressive symptoms ( relative risk [ RR ] , 2.0 ; 95 % confidence interval [ CI ] , 1.0 - 3.8 ) . Among women with CD4 cell counts of less than 200 x 10(6)/L , HIV-related mortality rates were 54 % for those with chronic depressive symptoms ( RR , 4.3 ; 95 % CI , 1.6 - 11.6 ) and 48 % for those with intermittent depressive symptoms ( RR , 3.5 ; 95 % CI , 1.1 - 10.5 ) compared with 21 % for those with limited or no depressive symptoms . Chronic depressive symptoms were also associated with significantly greater decline in CD4 cell counts after controlling for other variables in the model , especially among women with baseline CD4 cell counts of less than 500 x 10(6)/L and baseline viral load greater than 10 000 copies/microL. CONCLUSIONS Our results indicate that depressive symptoms among women with HIV are associated with HIV disease progression , controlling for clinical , substance use , and sociodemographic characteristics . These results highlight the importance of adequate diagnosis and treatment of depression among women with HIV . Further research is needed to determine if treatment of depression can not only enhance the mental health of women with HIV but also impede disease progression and mortality Abstract The present study evaluated the efficacy of an individualized psycho-education ( PE ) program in reducing psychological distress and risky sexual behavior and enhancing self-disclosure associated with an HIV diagnosis among attendees of a walk-in non-governmental voluntary counseling and testing ( VCT ) center in Nigeria . Ninety-four consecutive individuals were asked to complete a pre-counseling , baseline question naire detailing their sociodemographic characteristics , psychopathology , sexual practice s , self-disclosure intention and coping behaviors . They were screened for HIV and post-test counseled . Sixty-seven individuals ( 72.2 % ) who tested positive were consecutively r and omly assigned to one of two groups : a PE program ( four 60-minute weekly manual driven sessions ) ( N=34 ) and a wait-list ( WL ) control group ( N=33 ) . The major outcome measures used were the Crown Crisp Experiential Index ( CCEI ) , the Beck Depression Inventory ( BDI ) ( Beck et al. , ( 1961 ) , self-report sexual practice s in past three months , self-disclosure intention and the brief COPE . At four weeks post-intervention , significant reductions on all measures as well as reduction in risky sexual practice s were observed in the treatment group compared with the wait-list group . Treatment group members were also significantly more likely to disclose their serostatus and accept their HIV status as a way of coping , compared with the wait-list group . Overall , support was found for the efficacy of a manual-driven PE program for self-disclosure , reduction of depression and improvement in safe sexual practice 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 ) Objective . Tuberculosis and HIV coinfection poses unique clinical and psychosocial complexities that can impact nonadherence to highly active antiretroviral treatment ( HAART ) . Methods . This was a prospect i ve case series to identify risk factors for HAART nonadherence among 43 patients with HIV and tuberculosis ( TB ) in Lima , Peru . Nonadherence was defined by patient self-report . Results . The median initial CD4 and HIV viral load were 63 and 159,000 , respectively . Patients had received a median of 6.1 months of ART . Univariable analysis found low social support , substance use , and depression to be associated with nonadherence . In multivariable analysis , low social support was associated with nonadherence . Conclusions . In the authors ' urban cohort of HIV-TB coinfected individuals in Lima , Peru , substance use , depression , and lack of social support were key barriers to adherence . These findings suggest that adherence interventions may be unsuccessful unless they target the underlying psychosocial challenges faced by patients living with TB and AIDS |
13,529 | 25,169,727 | A reduction in SCD but not all-cause mortality was found in people with recent MI .
CRT-P and CRT-D reduced mortality and HF hospitalisations , and improved other outcomes , in people with HF as a result of LVSD and cardiac dyssynchrony when compared with OPT .
The rate of SCD was lower with CRT-D than with CRT-P but other outcomes were similar .
In people with both conditions , CRT-D reduced the risk of all-cause mortality and HF hospitalisation , and improved other outcomes , compared with ICDs . | BACKGROUND This assessment up date s and exp and s on two previous technology assessment s that evaluated implantable cardioverter defibrillators ( ICDs ) for arrhythmias and cardiac resynchronisation therapy ( CRT ) for heart failure ( HF ) .
OBJECTIVES To assess the clinical effectiveness and cost-effectiveness of ICDs in addition to optimal pharmacological therapy ( OPT ) for people at increased risk of sudden cardiac death ( SCD ) as a result of ventricular arrhythmias despite receiving OPT ; to assess CRT with or without a defibrillator ( CRT-D or CRT-P ) in addition to OPT for people with HF as a result of left ventricular systolic dysfunction ( LVSD ) and cardiac dyssynchrony despite receiving OPT ; and to assess CRT-D in addition to OPT for people with both conditions . | AIMS Whilst the CArdiac REsynchronization in Heart Failure ( CARE-HF ) trial has shown that cardiac resynchronization therapy ( CRT ) leads to reduced morbidity and mortality , the cost-effectiveness of this therapy remains uncertain . The aim of this study was to evaluate the incremental cost per quality adjusted life year ( QALY ) gained and incremental cost per life year gained of CRT plus medical therapy compared to medical therapy alone . METHODS AND RESULTS This prospect i ve analysis based on intention to treat data from all patients enrolled in the CARE-HF trial at 82 clinical centres in 12 European countries . A total of 813 patients with New York Heart Association class III or IV heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony were r and omized to CRT plus medical therapy ( n = 409 ) vs. medical therapy alone ( n = 404 ) . During a mean follow-up of 29.4 months CRT was associated with increased costs ( 4316 , 95 % CI : 1327 - 7485 ) , survival ( 0.10 years , 95 % CI : -0.01 - 0.21 ) , and QALYs ( 0.22 , 95 % CI : 0.13 - 0.32 ) . The incremental cost-effectiveness ratio was 19 319 per QALY gained ( 95 % CI : 5482 - 45 402 ) and 43 596 per life-year gained ( 95 % CI : -146 236 - 223 849 ) . These results were sensitive to the costs of the device , procedure , and hospitalization . CONCLUSION Treatment with CRT appears cost-effective at the notional willingness to pay threshold of 29 400 ( 20,000 pounds sterlings ) per QALY gained OBJECTIVES The evaluation of the risk of recurring heart failure events ( HFEs ) was a pre-specified sub study of MADIT-CRT ( Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy ) . BACKGROUND There are limited data regarding the effect of cardiac resynchronization therapy with a defibrillator ( CRT-D ) on the occurrence of recurring heart failure episodes after a first post-implantation HFE . METHODS Data with regard to recurring HFEs were prospect ively collected for all 1,820 MADIT-CRT participants . The CRT-D versus defibrillator-only risk for nonfatal first- and subsequent-HFEs was assessed by Cox proportional hazards and And ersen-Gill proportional intensity regression modeling , respectively , in efficacy analyses recognizing active device-type during follow-up . RESULTS Multivariate analysis showed that CRT-D was associated with a significant reduction in the risk of a first HFE ( hazard ratio [ HR ] : 0.54 , 95 % confidence interval [ CI ] : 0.44 to 0.67 , p < 0.001 ) and with a similar magnitude of reduction in the risk of HFEs subsequent to a first post-enrollment event ( HR : 0.62 , 95 % CI : 0.45 to 0.85 , p = 0.003 ) . The benefit of CRT-D for the prevention of first and subsequent HFEs was pronounced among patients with left bundle branch block ( HR : 0.38 , 95 % CI : 0.29 to 0.49 , p < 0.001 ; and HR : 0.50 , 95 % CI : 0.33 to 0.76 , p = 0.001 , respectively ) and nonsignificant in non-left bundle branch block patients ( HR : 1.12 , 95 % CI : 0.77 to 1.64 , p = 0.55 ; and HR : 0.99 , 95 % CI : 0.58 to 1.69 , p = 0.96 , respectively ; p values for interaction : p < 0.001 and p = 0.06 , respectively ) . The occurrences of first and second HFEs were associated with 7- and nearly 19-fold respective increases in the risk of subsequent mortality . CONCLUSIONS In the MADIT-CRT trial , the benefit of cardiac resynchronization therapy for the reduction in recurring HFEs was maintained after the occurrence of a first post-enrollment event . The occurrence of HFEs greatly increased the risk of death . ( Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy ; NCT00180271 ) BACKGROUND We conducted a prospect i ve , multicenter , r and omized comparison of implantable cardioverter-defibrillator ( ICD ) versus antiarrhythmic drug therapy in survivors of cardiac arrest secondary to documented ventricular arrhythmias . METHODS AND RESULTS From 1987 , eligible patients were r and omized to an ICD , amiodarone , propafenone , or metoprolol ( ICD versus antiarrhythmic agents r and omization ratio 1:3 ) . Assignment to propafenone was discontinued in March 1992 , after an interim analysis conducted in 58 patients showed a 61 % higher all-cause mortality rate than in 61 ICD patients during a follow-up of 11.3 months . The study continued to recruit 288 patients in the remaining 3 study groups ; of these , 99 were assigned to ICDs , 92 to amiodarone , and 97 to metoprolol . The primary end point was all-cause mortality . The study was terminated in March 1998 , when all patients had concluded a minimum 2-year follow-up . Over a mean follow-up of 57+/-34 months , the crude death rates were 36.4 % ( 95 % CI 26.9 % to 46.6 % ) in the ICD and 44.4 % ( 95 % CI 37.2 % to 51.8 % ) in the amiodarone/metoprolol arm . Overall survival was higher , though not significantly , in patients assigned to ICD than in those assigned to drug therapy ( 1-sided P=0.081 , hazard ratio 0.766 , [ 97.5 % CI upper bound 1.112 ] ) . In ICD patients , the percent reductions in all-cause mortality were 41.9 % , 39.3 % , 28 . 4 % , 27.7 % , 22.8 % , 11.4 % , 9.1 % , 10.6 % , and 24.7 % at years 1 to 9 of follow-up . CONCLUSIONS During long-term follow-up of cardiac arrest survivors , therapy with an ICD is associated with a 23 % ( nonsignificant ) reduction of all-cause mortality rates when compared with treatment with amiodarone/metoprolol . The benefit of ICD therapy is more evident during the first 5 years after the index event Background —Implantable cardioverter defibrillator ( ICD ) use reduces mortality in patients with serious ventricular arrhythmias compared with antiarrhythmic drug ( AAD ) use . However , the relative impact of these therapies on self-perceived quality of life ( QoL ) is unknown . Methods and Results —Three self-administered instruments were used to measure generic and disease-specific QoL in Antiarrhythmics Versus Implantable Defibrillators trial participants . Generalized linear models were used to assess the relationships between self-perceived QoL and treatment ( AAD versus ICD ) and adverse symptoms and ICD shocks . To minimize the impact of missing data , only patients surviving 1 year were included in the primary analyses . Baseline characteristics among QoL participants ( n=905 ) and non participants ( n=111 ) were similar , but participants who survived 1 year ( n=800 ) were healthier at baseline than nonsurvivors ( n=105 ) . Of the 800 patients in the primary analysis , characteristics of those r and omized to AAD ( n=384 ) versus ICD ( n=416 ) were similar . Overall , ICD and AAD use were associated with similar alterations in QoL. The development of sporadic shocks and adverse symptoms were each associated with reduced physical functioning and mental well-being and increased concerns among ICD recipients , whereas development of adverse symptoms was associated with reduced physical functioning and increased concerns among AAD recipients . Conclusions —ICD and AAD therapy are associated with similar alterations in self-perceived QoL over 1-year follow-up . Adverse symptoms were associated with reduced self-perceived QoL in both groups , and sporadic shocks were associated with reduced QoL in ICD recipients BACKGROUND To date , the implantable cardioverter-defibrillator ( ICD ) has been shown to be effective for primary prevention of sudden cardiac death only in selected groups of patients in the chronic phase after myocardial infa rct ion . METHODS AND RESULTS The Immediate Risk-Stratification Improves Survival ( IRIS ) Study compares ICD therapy with no ICD therapy in selected high risk patients early after myocardial infa rct ion . Special emphasis is placed on optimal acute and long term medical therapy in all patients including metoprolol CR/ZOK . The hypothesis is tested that use of the ICD reduces overall mortality . For that purpose , consecutive acute ST elevation or non-ST elevation myocardial infa rct ion patients are collected in a registry . From this denominator , patients are screened , and enrolled early after myocardial infa rct ion ( day 5 to day 31 ) if they exhibit both a reduced left ventricular ejection fraction < or = 40 % and a heart rate > or = 100 bpm on the first available electrocardiogram ( criterion I ) , or non-sustained ventricular tachycardia at a rate > or = 150 bpm during Holter ( criterion II ) . CONCLUSIONS IRIS is a large scale prospect i ve , r and omized trial to evaluate the benefit of ICD therapy for reduction of total mortality in patients considered at high risk of sudden death early after acute myocardial infa rct ion BACKGROUND Although pharmacological therapy has ameliorated symptoms and improved the survival of patients with chronic heart failure ( CHF ) , this chronic syndrome remains a progressive disease causing incremental morbidity and early mortality . A new therapy for the treatment of CHF should ideally decrease mortality , alleviate symptoms , and improve functional capacity . A growing body of evidence suggests that the use of implantable devices to resynchronize ventricular contraction may be a beneficial adjunct in the treatment of CHF . METHODS The Comparison of Medical Therapy , Pacing , and Defibrillation in Chronic Heart Failure ( COMPANION ) trial is a r and omized , open-label , 3-arm study of patients in New York Heart Association class III or IV with an ejection fraction of 35 % or less and a QRS duration of 120 milliseconds or less . The COMPANION study objectives are to determine whether optimal pharmacological therapy used with ( 1 ) ventricular resynchronization therapy alone or ( 2 ) ventricular resynchronization therapy combined with cardioverter-defibrillator capability is superior to optimal pharmacological therapy alone in reducing combined all-cause mortality and hospitalizations ; reducing cardiac morbidity ; improving functional capacity , cardiac performance , and quality of life ; and increasing total survival OBJECTIVES This study analyzed the causes of death in the Antiarrhythmics Versus Implantable Defibrillators ( AVID ) Trial . BACKGROUND Both implantable cardioverter-defibrillators ( ICDs ) and antiarrhythmic drugs ( AADs ) are used as mainstays of treatment for life-threatening ventricular arrhythmias in patients who have survived either ventricular fibrillation or sustained ventricular tachycardia with hemodynamic compromise and serious symptoms . The AVID Trial compared the effectiveness of these two therapies . Survival was better with the ICD . Assessment of the cause of death should help to determine the mechanism of improvement in survival with the ICD . METHODS Of 1,016 patients enrolled in the AVID Trial , 202 patients died . The mode of death was determined by the unblinded Principal Investigator and independently by an Events Committee , which review ed material s meticulously blinded with respect to treatment . Deaths were classified as cardiac or noncardiac . Cardiac deaths were further classified as arrhythmic or nonarrhythmic , and causes of noncardiac death were identified . RESULTS Deaths were more frequent in patients treated with an AAD ( n = 122 ) , compared with patients treated with the ICD ( n = 80 ) , unadjusted p < 0.001 , p = 0.012 adjusted for sequential monitoring . In AVID , 157 deaths were cardiac , and 79 were arrhythmic . The major effect of the ICD was to prevent arrhythmic death ( AAD = 55 , ICD = 24 , nominal unadjusted p < 0.001 ) . Nonarrhythmic cardiac deaths were equal ( AAD = 39 , ICD = 39 ) . Patients treated with an AAD had a slightly greater incidence of noncardiac deaths ( 28 vs. 17 , p = 0.053 ) , primarily due to pulmonary and renal causes . CONCLUSIONS The ICD is more effective than an AAD in reducing arrhythmic cardiac death , while nonarrhythmic cardiac death is unchanged . Of note , apparent arrhythmic death still seems to constitute 38 % of all cardiac deaths despite treatment with an ICD . However , the ICD remains superior to an AAD in prolonging survival after life-threatening arrhythmias OBJECTIVES This study was design ed to investigate whether selected baseline variables and early response markers predict the effects of cardiac resynchronization therapy ( CRT ) on long-term mortality . BACKGROUND Cardiac resynchronization therapy reduces long-term morbidity and mortality in patients with moderate or severe heart failure and markers of cardiac dyssynchrony , but not all patients respond to a similar extent . METHODS In the CARE-HF ( Cardiac Resynchronization in Heart Failure ) study , 813 patients with heart failure and markers of cardiac dyssynchrony were r and omly assigned to receive or not receive CRT in addition to pharmacological treatment and were followed for a median of 37.6 months . A model including assigned treatment , 15 pre-specified baseline variables , and 8 markers of response at 3 months was constructed to predict all-cause mortality . RESULTS On multivariable analysis , plasma concentration of amino terminal pro-brain natriuretic peptide ( univariate and multivariable model chi-square test : 105.0 and 48.4 ; both p < 0.0001 ) and severity of mitral regurgitation ( chi-square test : 44.0 and 17.9 ; both p < 0.0001 ) at 3 months , regardless of assigned treatment , were the strongest predictors of mortality . Ischemic heart disease as the cause of ventricular dysfunction ( chi-square test : 34.9 and 7.4 ; p < 0.0001 and p = 0.0066 ) , being in New York Heart Association functional class IV ( chi-square test : 18.8 and 9.6 ; p < 0.0001 and p = 0.0020 ) , or having less interventricular mechanical delay ( chi-square test : 29.8 and 8.8 ; p < 0.0001 and p = 0.0029 ) at baseline all predicted a worse outcome . However , the reduction in mortality in patients assigned to CRT was similar before ( hazard ratio : 0.602 ; 95 % confidence interval : 0.468 to 0.774 ) and after ( hazard ratio : 0.679 ; 95 % confidence interval : 0.494 to 0.914 ) adjustment for variables measured at baseline and at 3 months . CONCLUSIONS Patients who have more severe mitral regurgitation or persistently elevated amino terminal pro-brain natriuretic peptide despite treatment for heart failure , including CRT , have a higher mortality . However , patients assigned to CRT had a lower mortality even after adjusting for variables measured before and 3 months after intervention . The effect of CRT on mortality can not be usefully predicted using such information . ( CARE-HF CArdiac Resynchronization in Heart Failure ; NCT00170300 ) BACKGROUND The incidence of ventricular fibrillation ( VF ) as the presenting rhythm in out-of-hospital cardiac arrest ( OHCA ) is declining , whereas pulseless electrical activity ( PEA ) is increasing . This changing epidemiology has occurred concomitant with an increase in beta-blocker use . AIMS The aim of this study was to measure the association of beta-blocker use among prehospital cardiac arrest patients with PEA versus VF as presenting rhythm . MATERIAL S AND METHODS In this retrospective cohort study , records of all OHCA patients presenting to a single municipal hospital between 1 January 2001 and 31 December 2006 were review ed . Age , sex , race , first documented rhythm , estimated down time , presence of byst and er CPR , return of spontaneous circulation , beta-blocker use , and comorbid illnesses were noted . A Mantel-Haenzel chi-square was computed to describe the association between beta-blocker use and PEA , compared to beta-blocker use and VF . A sensitivity analysis was also performed to account for missing data , misclassification of beta-blocker use , misclassification of initial rhythm , confounding by unknown factors , and r and om error . RESULTS After exclusion of patients with asystole and patients in whom beta-blocker use was unclear/unknown , a cohort of 179 arrests was evaluated . The odds ratio for beta-blocker use among PEA versus VF patients was 3.7 ( 95 % CI 1.9 - 7.2 ) , and probabilistic adjustment for exposure and outcome misclassification , confounding , and r and om error increased the odds ratio to 5.0 ( 95 % CI 1.1 - 31.0 ) . CONCLUSIONS There appears to be an association between beta-blockers and the changing epidemiology of arrest rhythms , which may account for the increasing incidence of PEA and concomitant decrease in VF OBJECTIVES The purpose of this multicenter r and omized trial was to compare total mortality during therapy with amiodarone or an implantable cardioverter-defibrillator ( ICD ) in patients with nonischemic dilated cardiomyopathy ( NIDCM ) and nonsustained ventricular tachycardia ( NSVT ) . BACKGROUND Whether an ICD reduces mortality more than amiodarone in patients with NIDCM and NSVT is unknown . METHODS One hundred three patients with NIDCM , left ventricular ejection fraction < or = 0.35 , and asymptomatic NSVT were r and omized to receive either amiodarone or an ICD . The primary end point was total mortality . Secondary end points included arrhythmia-free survival , quality of life , and costs . RESULTS The study was stopped when the prospect i ve stopping rule for futility was reached . The percent of patients surviving at one year ( 90 % vs. 96 % ) and three years ( 88 % vs. 87 % ) in the amiodarone and ICD groups , respectively , were not statistically different ( p = 0.8 ) . Quality of life was also similar with each therapy ( p = NS ) . There was a trend with amiodarone , as compared to the ICD , towards improved arrhythmia-free survival ( p = 0.1 ) and lower costs during the first year of therapy ( $ 8,879 US dollars vs. $ 22,039 US dollars , p = 0.1 ) . CONCLUSIONS Mortality and quality of life in patients with NIDCM and NSVT treated with amiodarone or an ICD are not statistically different . There is a trend towards a more beneficial cost profile and improved arrhythmia-free survival with amiodarone therapy OBJECTIVES This study was conducted to assess the safety and effectiveness of cardiac resynchronization therapy ( CRT ) when combined with an implantable cardioverter defibrillator ( ICD ) . BACKGROUND Long-term outcome of CRT was measured in patients with symptomatic heart failure ( HF ) , intraventricular conduction delay , and malignant ventricular tachyarrhythmias ( ventricular tachycardia/ventricular fibrillation [ VT/VF ] ) requiring therapy from an ICD . METHODS Patients ( n = 490 ) were implanted with a device capable of providing both CRT and ICD therapy and r and omized to CRT ( n = 245 ) or control ( no CRT , n = 245 ) for up to six months . The primary end point was progression of HF , defined as all-cause mortality , hospitalization for HF , and VT/VF requiring device intervention . Secondary end points included peak oxygen consumption ( VO(2 ) ) , 6-min walk ( 6 MW ) , New York Heart Association ( NYHA ) class , quality of life ( QOL ) , and echocardiographic analysis . RESULTS A 15 % reduction in HF progression was observed , but this was statistically insignificant ( p = 0.35 ) . The CRT , however , significantly improved peak VO(2 ) ( 0.8 ml/kg/min vs. 0.0 ml/kg/min , p = 0.030 ) and 6 MW ( 35 m vs. 15 m , p = 0.043 ) . Changes in NYHA class ( p = 0.10 ) and QOL ( p = 0.40 ) were not statistically significant . The CRT demonstrated significant reductions in ventricular dimensions ( left ventricular internal diameter in diastole = -3.4 mm vs. -0.3 mm , p < 0.001 and left ventricular internal diameter in systole = -4.0 mm vs. -0.7 mm , p < 0.001 ) and improvement in left ventricular ejection fraction ( 5.1 % vs. 2.8 % , p = 0.020 ) . A subgroup of patients with advanced HF ( NYHA class III/IV ) consistently demonstrated improvement across all functional status end points . CONCLUSIONS The CRT improved functional status in patients indicated for an ICD who also have symptomatic HF and intraventricular conduction delay More than 1 million Americans per year have acute myocardial infa rct ion ( 1 ) . Those who survive to hospital discharge have a 5 % to 10 % risk for dying suddenly within the first year ( 27 ) . Prevention of those sudden deaths is an important goal , and several approaches have been used to accomplish it . Secondary prevention with type I antiarrhythmic drugs has been unsuccessful ( 8) . Prophylactic use of amiodarone has significantly reduced death after myocardial infa rct ion in some but not all r and omized trials . Quantitative overviews of these studies suggest that amiodarone reduces mortality rates by 10 % to 20 % ( 9 , 10 ) . Recent studies of the implantable cardioverter defibrillator ( ICD ) in patients who have no history of sustained arrhythmia have also had mixed results , with positive results in patients with unsustained ventricular tachycardia ( 11 , 12 ) and negative results in patients with reduced ejection fraction and positive results on signal-averaged electrocardiography ( 13 ) . The use of prophylactic ICD has nevertheless attracted great interest because of the demonstrated efficacy of the device in patients who have had a documented episode of ventricular fibrillation or sustained ventricular tachycardia ( 1416 ) . Although ongoing or planned r and omized , controlled trials ( 17 , 18 ) will clarify the role of ICDs and amiodarone therapy in patients who have had myocardial infa rct ions , the results of these trials will not be available until late 2001 at the earliest . We previously showed that ICDs can be cost-effective in patients who have survived an episode of ventricular fibrillation or sustained ventricular tachycardia ( 19 ) . These findings can not be extrapolated to prophylactic use of ICDs in patients who have had myocardial infa rct ions because the risk for sudden death in such patients is lower . Indeed , the current st and ard of care for patients who have had myocardial infa rct ion does not include prophylactic antiarrhythmic therapy . With recent evidence of the efficacy of antiarrhythmia management in patients who have had myocardial infa rct ions , the potential cost-effectiveness of prophylactic antiarrhythmic therapy should be reassessed . In this study , we estimated survival and costs for patients with past myocardial infa rct ion who were treated with amiodarone , ICD , or no specific antiarrhythmic therapy . We evaluated the level of efficacy needed to make prophylactic therapy with an ICD or amiodarone cost-effective in three groups of patients with past myocardial infa rct ion who were stratified by left ventricular ejection fraction . Methods We used a decision model to estimate the length of life and expenditures for patients who had myocardial infa rct ion without symptomatic , sustained ventricular arrhythmia and who received one of three treatment strategies : ICD , amiodarone therapy , or no antiarrhythmic therapy ( Figure 1 ) . We stratified patients into three groups according to ejection fraction : less than or equal to 0.3 , 0.31 to 0.4 , and greater than 0.4 . Although the ability of many clinical factors to predict the risk for sudden cardiac death has been analyzed and several independent risk factors have been identified ( 20 ) , ejection fraction has consistently been the single most powerful predictor of sudden cardiac death ( 2124 ) . Figure 1 . The decision model . The square node on the left represents a choice among three alternative treatments : implantable cardiac defibrillator ( ICD ) , amiodarone , and no antiarrhythmic treatment . Circles represent chance nodes . Patients who receive an ICD are at risk for death from the implant procedure . Patients who do not die of ICD implantation and patients who are receiving amiodarone or no treatment enter the Markov tree ( denoted by rectangles containing circles and an arrow ) . The Markov tree represents the clinical events that can occur during each 1-month period as a patient is followed until death . During each 1-month period , a patient may die from arrhythmic or nonarrhythmic cardiac causes and may also die of noncardiac causes . If none of these events occur , the patient remains well for the 1-month period . Patients who have an ICD may have a lead infection or failure that causes them to withdraw from treatment ( and to switch to no antiarrhythmic therapy ) . Patients who receive amiodarone are at risk for amiodarone toxicity . In our analysis , a patient may die of toxicity , withdraw from treatment ( and switch to no antiarrhythmic therapy ) , or have acute toxicity that does not require discontinuation . We adhered to the recommendations of the Panel on Cost-effectiveness in Health and Medicine ( 25 , 26 ) . We used a societal perspective to evaluate health benefits and costs , discounting each at a rate of 3 % per year . We performed one-way sensitivity analyses on all of the model variables , as well as selected two-way , three-way , and n-way ( Monte Carlo ) probabilistic sensitivity analyses ( 27 ) . Decision Model We developed a Markov model ( 28 , 29 ) ( SMLTree decision analysis software , version 2.9 , J. Hollenberg , New York , New York ) by modifying a model used previously to assess the cost-effectiveness of ICDs or amiodarone in patients who had experienced sustained ventricular arrhythmia ( 19 , 30 ) ( Figure 1 ) . Our current model includes the possibility of no antiarrhythmic therapy and uses data relevant to the lower-risk population of patients who have survived myocardial infa rct ion . The model tracks a cohort of patients who received prophylactic ICD ( implanted without a thoracotomy ) , amiodarone therapy , or no antiarrhythmic therapy . Patients who received an ICD were at risk for procedural death . Patients who survived ICD implantation , patients treated with amiodarone , and patients who received no antiarrhythmic therapy entered a Markov tree ( Figure 1 ) . Each month , these patients were at risk for sudden cardiac death , nonsudden cardiac death , and noncardiac death . We assumed that 2 % of the ICD-treated patients would have the ICD removed because of infection or lead complications during the first year and that 1 % of surviving patients would withdraw from ICD therapy in each subsequent year ( 3133 ) . Similarly , we assumed that 10 % of the amiodarone-treated patients would withdraw from therapy because of toxicity during the first year and that 5 % of surviving patients would withdraw in each subsequent year ( 3445 ) . Because the use of antiarrhythmic therapy in the postmyocardial infa rct ion population would be prophylactic , we assumed that crossovers between the ICD and amiodarone strategies would be less likely . Therefore , patients who withdrew from one antiarrhythmic treatment would be withdrawn from prophylactic treatment . Patient Sample Our base-case analyses evaluated the cost-effectiveness of each antiarrhythmic management strategy in three cohorts of patients defined by ejection fraction ( Table 1 ) . We obtained mortality and inpatient cost data for patients from the Myocardial Infa rct ion Triage and Intervention ( MITI ) patient registry ( 46 ) who had had myocardial infa rct ion . Between 1988 and 1994 , approximately 40 000 patients were admitted to cardiac care units in 19 hospitals in Seattle , Washington . Hospitals participating in the registry include 2 university hospitals , 2 staff-model health maintenance organization hospitals , 1 Veterans Affairs hospital , and 14 community hospitals . During most of the study period , 10 of the participating hospitals had on-site catheterization laboratories and 5 performed bypass surgery . During the study period , 12 000 patients presented with an acute myocardial infa rct ion ; of these , ejection fraction was measured in approximately 3000 . Table 1 . Clinical Characteristics of the Myocardial Infa rct ion Triage and Intervention Patient Sample Patients with ejection fractions of 0.3 or less had a mean age ( SD ) of 66.5 11.92 years ( range , 26 to 95 years ) , 24.6 % 43.1 % had a history of congestive heart failure , 62.8 % 48.4 % received an initial catheterization , and 26.6 % 44.3 % underwent initial revascularization . Patients with ejection fractions between 0.31 and 0.4 had a mean age of 63.5 12.22 years ( range , 36 to 97 years ) , 11.0 % 31.3 % had a history of congestive heart failure , 73.2 % 44.3 % underwent catheterization , and 37.6 % 48.4 % had revascularization . Finally , patients with ejection fractions greater than 0.4 had a mean age of 61.5 11.83 years ( range , 26 to 92 years ) , 3.5 % 18.4 % had a history of congestive heart failure , 88.0 % 32.4 % received an initial catheterization , and 48.0 % 50 % underwent revascularization . We compared the characteristics of patients who had ejection fraction measurements with those of patients in the MITI registry for whom ejection fraction was not measured . The clinical characteristics listed in Table 1 differed significantly between these groups , but the rates of sudden cardiac , nonsudden cardiac , noncardiac , and overall mortality did not differ significantly after we controlled for age , sex , and cardiac history ( 24 ) . From the MITI registry , we obtained monthly probabilities of cardiac death for the three ejection fraction cohorts . The MITI project used hospital discharge summaries and death certificates to identify patients who died of cardiac causes during follow-up while in or out of the hospital ( 47 ) . We classified cardiac deaths that occurred in neither a hospital nor a nursing home as sudden and potentially preventable by arrhythmic therapy ; we classified as nonsudden the cardiac deaths that occurred in a hospital or a nursing home . We recognized the limitations of this classification system and therefore analyzed a range of ICD efficacies . Table 1 summarizes the probabilities of sudden and nonsudden cardiac death for the three cohorts over time . To estimate life expectancy after the end of follow-up in the MITI cohort , we extrapolated the annual cardiac mortality rate for subsequent years from that observed during follow-up and assumed that the noncardiac mortality rate would equal that in the general U.S. population ( 48 ) . Effectiveness of Background —Phrenic stimulation ( PS ) may hinder left ventricular ( LV ) pacing . We prospect ively observed its prevalence in consecutive patients with cardiac resynchronization therapy ( CRT ) devices . Methods and Results —In the years 2003 to 2006 , 197 patients received a CRT device . PS and LV threshold measurements were carried out at implantation and at 6-month follow-up . LV reverse remodeling was assessed by echocardiography before implantation and at follow-up . LV lead placement was lateral/posterolateral in 86 % of patients . Both PS and LV reverse remodeling occurred most frequently at the lateral/posterolateral LV pacing sites ( P<0.001 ) . PS was detected in 73 ( 37 % ) of patients and was clinical ly relevant in 41 ( 22 % ) . The detection of PS at implantation had a poor sensitivity , as it occurred only in left lateral or sitting position in 27 patients . Ten patients ( 5 % ) underwent repeated surgery and 4 ( 2 % ) had their CRT turned off because of PS . At follow-up , we could manage PS noninvasively in 32 patients with a small PS-LV threshold difference : in 20 by cathode programmability ( 3 also thanks to automatic management of LV output ) and in 12 ( without cathode programmability ) by programming the LV output as threshold + 1 V. Conclusions —PS may seriously hinder CRT . A bipolar LV lead and cathode programmability are m and atory to avoid PS by changing the LV pacing vector at target sites for CRT . LV stability at target sites despite PS should also be pursued by these means . The automatic adjustment of LV pacing output is complementary in patients with a small PS-LV threshold difference Background —Although implantable cardioverter-defibrillators ( ICDs ) reduce mortality in primary prevention patients with left ventricular systolic dysfunction , recent studies have question ed their overall role in clinical practice , especially in older patients and those with major comorbid conditions . Methods and Results —In a prospect i ve cohort of 965 patients with ischemic and nonischemic cardiomyopathies ( ejection fraction ≤35 % ) and no prior ventricular arrhythmias , we compared long-term mortality in patients who did ( n=494 [ 51 % ] ) and did not receive ICDs over a mean follow-up period of 34±16 months . Using a l and mark analysis , multivariable Cox proportional hazards models that included propensity scores for ICD implantation assessed the relationship between ICD therapy and mortality in the entire cohort and by age and the presence of major comorbid conditions . Data from these analyses were then used as inputs in a Markov model to generate incremental cost-effectiveness ratios for ICD therapy . Patients who received ICDs were similar in age and prevalence of most major comorbid conditions , including symptomatic heart failure . After multivariable adjustment , ICD therapy was associated with a 31 % lower risk for all-cause mortality ( adjusted hazard ratio , 0.69 ; 95 % CI , 0.50 to 0.96 ; P=0.03 ) . The relationship between ICD therapy and lower all-cause mortality was consistent after stratification by age ( < 65 , 65 to 74 , and ≥75 ) , ischemic etiology , ejection fraction ( > 25 % versus ≤25 % ) , and the presence of major comorbid conditions ( probability values for all interactions > 0.05 ) . Incremental cost-effectiveness ratios for ICD therapy were similar between patients aged ≥75 years and younger patients but rose slightly in those with multiple comorbid conditions . Conclusions —Routine use of ICDs in primary prevention patients with left ventricular systolic dysfunction was associated with lower all-cause mortality , even among older patients and those with major comorbid conditions . Although their use needs to be individualized , our findings suggest that these groups should not be routinely excluded from ICD treatment Background —The implantable cardioverter-defibrillator ( ICD ) is an effective but expensive device . We used prospect ively collected data from a large r and omized clinical trial of secondary prevention of life-threatening ventricular arrhythmias to determine the cost-effectiveness of the ICD compared with antiarrhythmic drug ( AAD ) therapy , largely with amiodarone . Methods and Results —Charges for initial and repeat hospitalizations , emergency room , and day surgery stays and the costs of antiarrhythmic drugs were collected on 1008 patients . Detailed records of all other medical encounters and expenses were collected on a subgroup of 237 patients . Regression models were then created to attribute these expenses to the rest of the patients . Charges were converted to 1997 costs using st and ard methods . Costs and life years were discounted at 3 % per year . Three-year survival data from the Antiarrhythmics Versus Implantable Defibrillators trail were used to calculate the base-case cost-effectiveness ( C/E ) ratio . Six-year , twenty-year , and lifetime C/E ratios were also estimated . At 3 years , total costs were $ 71 421 for a patient taking AADs and $ 85 522 for a patient using an ICD , and the ICD provided a 0.21-year survival benefit over AAD treatment . The base-case C/E ratio was thus $ 66 677 per year of life saved by the ICD compared with AAD therapy ( 95 % CI , $ 30 761 to $ 154 768 ) . Six- and 20-year C/E ratios remained stable between $ 68 000 and $ 80 000 per year of life saved . Conclusions —The ICD is moderately cost-effective for secondary prevention of life-threatening ventricular arrhythmias , as judged from prospect ively collected data in a r and omized clinical trial Background —In the Canadian Implantable Defibrillator Study ( CIDS ) , we assessed the cost-effectiveness of the implantable cardioverter-defibrillator ( ICD ) in reducing the risk of death in survivors of previous ventricular tachycardia ( VT ) or fibrillation ( VF ) . Methods and Results —Healthcare re source use was collected prospect ively on the first 430 patients enrolled in CIDS ( n=212 ICD , n=218 amiodarone ) . Mean cost per patient , adjusted for censoring , was computed for each group based on initial therapy assignment . Incremental cost-effectiveness of ICD therapy was computed as the ratio of the difference in cost ( ICD minus amiodarone ) to the difference in life expectancy ( both discounted at 3 % per year ) . All costs are in 1999 Canadian dollars ( C$ 1 ≈ US$ 0.65 ) . Over 6.3 years , mean cost per patient in the ICD group was C$ 87 715 versus C$ 38 600 in the amiodarone group ( difference C$ 49 115 ; 95 % CI C$ 25 502 to C$ 69 508 ) . Life expectancy for the ICD group was 4.58 years versus 4.35 years for amiodarone ( difference 0.23 , 95 % CI −0.09 to 0.55 ) , for incremental cost-effectiveness of ICD therapy of C$ 213 543 per life-year gained . ICD benefit was greater in patients with low left ventricular ejection fraction ( < 35 % ) , and cost-effectiveness in this group was more attractive ( C$ 108 484 ) . Alternative extrapolations of survival benefit and costs to 12 years indicated cost-effectiveness in the range of C$ 100 000 to C$ 150 000 per life-year gained . Conclusions —At C$ 213 543 , the value for the money offered by ICD therapy is not attractive by currently accepted st and ards . Further research is warranted to identify the indications and patient subgroups for whom ICDs are a cost-effective use of re sources BACKGROUND Implantation of transvenous implantable cardioverter-defibrillators ( ICDs ) utilizing a non-thoracotomy approach has become routine therapy for survivors of life-threatening tachyarrhythmias . In the Antiarrhythmics versus Implantable Defibrillator ( AVID ) Trial , we sought to identify and prospect ively characterize the frequency of lead and ICD-related complications . Between June 1 , 1993 , and April 7 , 1997 , 539 patients received non-thoracotomy ICDs . A total of 62 first complications occurred . The subclavian route of insertion result ed in more complications than the cephalic vein route , 46 of 339 ( 14 % ) versus 6 of 135 ( 4 % ) , p = .005 as did the abdominal versus pectoral generator site ; 31 of 238 ( 13 % ) versus 17 of 291 ( 6 % ) , p < .02 . Most dislodgements and system infections tended to occur in the 3 months following implantation , whereas lead fractures continued to occur throughout follow-up . Failure to use peri-operative antibiotics was a predictor of system infection ( p = .001 ) . These data suggest that cephalic vein access and pectoral generator site may result in fewer complications . Although implantation techniques and generator technology continue to evolve , the continued occurrence of lead fractures and the need for premature system revision supports the practice of close routine ICD system surveillance BACKGROUND Implantable cardioverter-defibrillator ( ICD ) therapy has been shown to improve survival in patients with various heart conditions who are at high risk for ventricular arrhythmias . Whether benefit occurs in patients early after myocardial infa rct ion is unknown . METHODS We conducted the Defibrillator in Acute Myocardial Infa rct ion Trial , a r and omized , open-label comparison of ICD therapy ( in 332 patients ) and no ICD therapy ( in 342 patients ) 6 to 40 days after a myocardial infa rct ion . We enrolled patients who had reduced left ventricular function ( left ventricular ejection fraction , 0.35 or less ) and impaired cardiac autonomic function ( manifested as depressed heart-rate variability or an elevated average 24-hour heart rate on Holter monitoring ) . The primary outcome was mortality from any cause . Death from arrhythmia was a predefined secondary outcome . RESULTS During a mean ( + /-SD ) follow-up period of 30+/-13 months , there was no difference in overall mortality between the two treatment groups : of the 120 patients who died , 62 were in the ICD group and 58 in the control group ( hazard ratio for death in the ICD group , 1.08 ; 95 percent confidence interval , 0.76 to 1.55 ; P=0.66 ) . There were 12 deaths due to arrhythmia in the ICD group , as compared with 29 in the control group ( hazard ratio in the ICD group , 0.42 ; 95 percent confidence interval , 0.22 to 0.83 ; P=0.009 ) . In contrast , there were 50 deaths from nonarrhythmic causes in the ICD group and 29 in the control group ( hazard ratio in the ICD group , 1.75 ; 95 percent confidence interval , 1.11 to 2.76 ; P=0.02 ) . CONCLUSIONS Prophylactic ICD therapy does not reduce overall mortality in high-risk patients who have recently had a myocardial infa rct ion . Although ICD therapy was associated with a reduction in the rate of death due to arrhythmia , that was offset by an increase in the rate of death from nonarrhythmic causes Background —The Multicenter Unsustained Tachycardia Trial ( MUSTT ) was design ed to evaluate an antiarrhythmic treatment strategy , including drugs and implantable defibrillators ( ICDs ) , guided by electrophysiological ( EP ) testing . We performed several statistical analyses to assess the contribution of defibrillators to the observed treatment benefit . Methods and Results —First , the effects of defibrillators were indirectly examined by comparing the r and omized treatment arms ( EP-guided therapy versus no antiarrhythmic therapy ) within subgroups that varied according to ICD usage . Use of ICDs increased during the trial ; hence , the r and omized treatments were compared according to date of enrollment . There were also site-specific differences in ICD use ; hence , the r and omized arms were compared within groups of sites defined by level of ICD use . There was a distinct “ dose response ” in relation to ICD use . Where ICD use was high , EP-guided therapy produced significant reductions in arrhythmic death or cardiac arrest ( P < 0.004 ) . Where ICD use was low , there was no benefit of EP-guided therapy . Finally , outcomes of EP-guided therapy patients who received an ICD were directly compared with outcomes of other patients using the Cox proportional hazards model with receipt of an ICD as a time-dependent covariate . Adjusted for other prognostic factors , patients who received an ICD had risk reductions of > 70 % in arrhythmic death or cardiac arrest and > 50 % in total mortality ( P < 0.001 for both end points ) . Conclusions —The benefit of EP-guided antiarrhythmic therapy observed in MUSTT was due to improved outcomes among patients who received an ICD but not among patients who received antiarrhythmic drugs BACKGROUND The CABG Patch trial compared prophylactic implantable cardiac-defibrillator ( ICD ) implantation with no antiarrhythmic therapy in coronary bypass surgery patients who had a left ventricular ejection fraction < 0.36 and an abnormal signal-averaged ECG . There were 102 deaths among the 446 ICD group patients and 96 deaths among the 454 control group patients , a hazard ratio of 1.07 ( P=0.63 ) . The mechanisms of death were classified , and hypotheses were tested about the effects of ICD therapy on arrhythmic and nonarrhythmic cardiac deaths in the CABG Patch Trial and the Multicenter Automatic Defibrillator Implantation Trial ( MADIT ) . METHODS AND RESULTS The 198 deaths in the trial were review ed by an independent Events Committee and classified by the method of Hinkle and Thaler . Only 54 deaths ( 27 % ) occurred out of hospital ; 145 deaths ( 73 % ) were witnessed . Seventy-nine ( 82 % ) of the 96 deaths in the control group and 76 ( 75 % ) of the 102 deaths in the ICD group were due to cardiac causes . Cumulative arrhythmic mortality at 42 months was 6.9 % in the control group and 4.0 % in the ICD group ( P=0 . 057 ) . Cumulative nonarrhythmic cardiac mortality at 42 months was 12 . 4 % in the control group and 13.0 % in the ICD group ( P=0.275 ) . Death due to pump failure was significantly associated with death > 1 hour from the onset of symptoms , dyspnea within 7 days of death , and overt heart failure within 7 days of death . CONCLUSIONS In the CABG Patch Trial , ICD therapy reduced arrhythmic death 45 % without significant effect on nonarrhythmic deaths . Because 71 % of the deaths were nonarrhythmic , total mortality was not significantly reduced BACKGROUND The Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation study demonstrated that implantable cardioverter defibrillators ( ICDs ) significantly reduce the risk of sudden cardiac death in patients with nonischemic cardiomyopathy and an ejection fraction of 35 % or less , with no statistically significant decrease in overall mortality . The impact of ICD placement and shock on health-related quality of life ( HRQL ) in this population is unknown . METHODS The 12-Item Medical Outcomes Short-Form Health Survey and the Minnesota Living with Heart Failure Question naire were administered to 458 patients with nonischemic cardiomyopathy , an ejection fraction of 35 % or less , and either nonsustained ventricular tachycardia or 10 or more premature ventricular depolarizations per hour at baseline , 1 month after r and omization , and every 3 months thereafter throughout the trial . The subjects were r and omized to an ICD or st and ard medical therapy . Outcomes were compared using hierarchical linear regression . RESULTS Overall , there were no significant differences in HRQL throughout the trial between patients r and omized to an ICD or st and ard medical therapy . However , in patients with 1 or more ICD shocks , HRQL declined 0.5 + /- 0.2 ( mean + /- SD ) points per shock on the emotional scale of the Minnesota Living with Heart Failure Question naire ( P = .04 ) and 1.0 + /- 0.5 points per shock on the mental component score of the 12-Item Medical Outcomes Short-Form Health Survey ( P = .04 ) . CONCLUSIONS Overall , HRQL was not affected by ICD implantation in patients in the Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation study . Implantable cardioverter defibrillator shock was associated with a reduction in some measures of HRQL , but the effects were unlikely to result in a clinical ly observable alteration until 5 or more shocks were experienced Background — The Sudden Cardiac Death in Heart Failure Trial ( SCD-HeFT ) demonstrated that implantable cardioverter-defibrillator ( ICD ) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction ≤35 % on optimal medical therapy . Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown . Methods and Results — SCD-HeFT r and omized 2521 subjects to placebo , amiodarone , or shock-only , single-lead ICD therapy . Over a median follow-up of 45.5 months , a total of 666 deaths occurred , which were review ed by an Events Committee and initially categorized as cardiac or noncardiac . Cardiac deaths were further adjudicated as result ing from sudden death presumed to be ventricular tachyarrhythmic , bradyarrhythmia , heart failure , or other cardiac causes . ICD therapy significantly reduced cardiac mortality compared with placebo ( adjusted hazard ratio , 0.76 ; 95 % confidence interval , 0.60 to 0.95 ) and tachyarrhythmia mortality ( adjusted hazard ratio , 0.40 ; 95 % confidence interval , 0.27 to 0.59 ) and had no impact on mortality result ing from heart failure or noncardiac causes . The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure . The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease . Compared with placebo , amiodarone had no significant effect on any mode of death . Conclusions — ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality . Amiodarone had no effect on all-cause mortality or its cause-specific components , except an increase in non-cardiac mortality in class III patients . Clinical Trial Registration Information— URL : http://www . clinical trials.gov . Unique identifier : NCT00000609 Background —Sudden Unexplained Death Syndrome ( SUDS ) is the leading cause of death in young , healthy , Southeast Asian men . The role of an implantable cardioverter defibrillator ( ICD ) for mortality reduction in these patients remains unclear . Methods and Results —The Defibrillator Versus & bgr;-Blockers for Unexplained Death in Thail and ( DEBUT ) study is a r and omized , clinical trial conducted in 2 phases ( pilot study followed by the main trial ) to compare the annual all-cause mortality rates among SUDS patients treated with & bgr;-blockers versus that among those treated with an ICD . A total of 86 patients who were SUDS survivors and probable SUDS survivors were r and omized to receive an ICD or propranolol ( 20 patients were in the pilot study and 66 were in the main trial ) . The primary end point was death from all causes . The secondary end point was recurrent ventricular tachycardia/ventricular fibrillation ( VF ) or cardiac arrest . During the 3-year follow-up period of the main trial , there were 4 deaths ; all occurred in the & bgr;-blocker group ( P = 0.02 ) . Seven subjects in the ICD arm had recurrent VF , and all were effectively treated by the ICD . On the basis of the main trial results , the Data Safety Monitoring Board stopped the study . In total ( both from the Pilot study and the main trial ) , there were 7 deaths ( 18 % ) in the & bgr;-blocker group and no deaths in the ICD group , but there were a total of 12 ICD patients receiving ICD discharges due to recurrent VF . Conclusions —ICD treatment provides full protection from death related to primary VF in a SUDS population and is superior to & bgr;-blockade treatment Background —Cardiac resynchronization therapy ( CRT ) has recently emerged as an effective treatment for patients with moderate to severe systolic heart failure and ventricular dyssynchrony . The purpose of the present study was to determine whether improvements in left ventricular ( LV ) size and function were associated with CRT . Methods and Results —Doppler echocardiograms were obtained at baseline and at 3 and 6 months after therapy in 323 patients enrolled in the Multicenter InSync R and omized Clinical Evaluation ( MIRACLE ) trial . Of these , 172 patients were r and omized to CRT on and 151 patients to CRT off . Measurements were made of LV end-diastolic and end-systolic volumes , ejection fraction , LV mass , severity of mitral regurgitation ( MR ) , peak transmitral velocities during early ( E-wave ) and late ( A-wave ) diastolic filling , and the myocardial performance index . At 6 months , CRT was associated with reduced end-diastolic and end-systolic volumes ( both P < 0.001 ) , reduced LV mass ( P < 0.01 ) , increased ejection fraction ( P < 0.001 ) , reduced MR ( P < 0.001 ) , and improved myocardial performance index ( P < 0.001 ) compared with control . & bgr;-Blocker treatment status did not influence the effect of CRT . Improvements with CRT were greater in patients with a nonischemic versus ischemic cause of heart failure . Conclusions —CRT in patients with moderate-to-severe heart failure who were treated with optimal medical therapy is associated with reverse LV remodeling , improved systolic and diastolic function , and decreased MR . LV remodeling likely contributes to the symptomatic benefits of CRT and may herald improved longer-term survival BACKGROUND Because the best possible device longevity is crucial ( i.e. , risk of infection with premature device exchange , current cost-effectiveness calculations depending on reasonable longevity , patient comfort ) , industry-independent real-life data are fundamental . However , only limited independent data on the longevity of implantable cardioverter-defibrillators ( ICDs ) are available . OBJECTIVE The purpose of this study was to determine ICD device longevity and influencing factors . METHODS From a prospect i ve data base , we studied overall device longevity and identified those devices with replacement for battery depletion or prolonged charge time . For every device , we determined factors that included averaged shocks , pacing percentage , pacing mode , device size , and time of implant . Survival probabilities at different time intervals were calculated , and Kaplan-Meier and Cox regression analyses were used . Observed longevity was compared to industry-projected longevity obtained from product performance reports . RESULTS A total of 644 ICDs ( Medtronic 317 , Guidant 189 , St. Jude 118 , Intermedics 20 ) were implanted in 499 patients . During follow-up , 163 ( 25.3 % ) ICDs were replaced . Manufacturer , time of implant , pacing mode , pacing percentage , and capacitor reformation interval influenced longevity , whereas device size and number of shocks did not . Median longevity was 7.6 years for Medtronic devices , 5.0 years for Guidant devices , and 3.8 years for St. Jude devices . After 5 years , only 70 % of ICDs were still in service compared to the 80 % projected by industry . CONCLUSION Marked differences in device longevity among manufacturers can not be explained by pacing mode , number of shocks , or pacing percentage only . Overall , device performance requires further improvement for the sake of patient health and cost BACKGROUND Many r and omized clinical trials have demonstrated the effectiveness of the implantable cardioverter-defibrillator ( ICDs ) in death reduction of chronic heart failure ( CHF ) patients . Some developed countries studies have evaluated its cost-effectiveness , but these data are not applicable to Brazil . OBJECTIVE To evaluate the cost-effectiveness of ICD in CHF patients under two perspectives in Brazil : public and supplementary health systems . METHODS A Markov model was developed to analyze the incremental cost-effectiveness ratio ( ICER ) of ICD compared to conventional therapy in patients with CHF . Effectiveness was measured in quality -adjusted life years ( QALYs ) . We search ed the literature for data regarding effectiveness and complications . Costs were retrieved from public and health insurances reimbursement codebooks and from mean cost of admissions from a public and a private hospital . One-way sensitivity analysis was performed in all variables of the model . RESULTS ICER was R$ 68,318/QALY in the public and R$ 90,942/QALY in the private perspective . These values are much higher than the one suggested by the World Health Organization of 3 times the gross domestic product per head ( R$ 40,545 in Brazil ) . The results were sensitive to the cost of the device , battery replacement interval and ICD effectiveness . In a simulation resembling MADIT-I population survival and ICD benefit , ICER was R$ R$ 23,739/QALY in the public and R$ 33,592/QALY in the private perspective . CONCLUSION The ICER of ICD is elevated in the general ICC population , in either the public or private perspective . A more favorable result occurs in patients with a high sudden death risk AIMS Heart failure ( HF ) is reported to have an essentially malignant prognosis that can be modified by several interventions . Most outcome data on HF are available from r and omized controlled treatment trials and longitudinal epidemiological studies . However , for a number of reasons , neither type of study have , to date , provided generalizable data on HF mortality . Furthermore , data on the prognosis of borderline left ventricular systolic dysfunction ( LVSD ) are even more limited . METHODS AND RESULTS ECHOES ( Echocardiographic Heart of Engl and Screening Study ) screened a total of 6,162 patients from a total of 10,161 invited ( 61 % response rate ) . Patients were r and omly selected from four pre-specified cohorts : the general population , diuretic users , those with a prior clinical label of HF , and a population with risk factors for HF , to identify the prevalence of HF and LVSD based on clinical assessment , ECG , and echocardiography . Causes of death during a 5 - 9 year follow-up period were recorded from routine mortality statistics . The 5-year survival rate of the general population was 93 % , compared with 69 % of those with LVSD without HF , 62 % with HF and no LVSD , and 53 % with HF plus LVSD . Survival improved significantly with increasing ejection fraction ( EF ) ( log rank test for trend , chi(2 ) = 534.5 , 1 , P < 0.0001 ) . CONCLUSION The ECHOES mortality data confirm the poor prognosis of patients suffering prevalent HF across the community with a mortality risk estimate of 9 % per year . Borderline systolic dysfunction ( EF 40 - 50 % ) on echocardiography carries a poor prognosis Background — Patients with idiopathic dilated cardiomyopathy ( DCM ) and impaired left ventricular ejection fraction have an increased risk of dying suddenly . Methods and Results — Patients with recent onset of DCM ( ≤9 months ) and an ejection fraction ≤30 % were r and omly assigned to the implantation of an implantable cardioverter-defibrillator ( ICD ) or control . The primary end point of the trial was all-cause mortality at 1 year of follow-up . The trial was terminated after the inclusion of 104 patients because the all-cause mortality rate at 1 year did not reach the expected 30 % in the control group . In August 2000 , the vital status of all patients was up date d by contacting patients , relatives , or local registration offices . One hundred four patients were enrolled in the trial : Fifty were assigned to ICD therapy and 54 to the control group . Mean follow-up was 22.8±4.3 months , on the basis of investigators ’ follow-up . After 1 year , 6 patients were dead ( 4 in the ICD group and 2 in the control group ) . No sudden death occurred during the first and second years of follow-up . In August 2000 , after a mean follow-up of 5.5±2.2 years , 30 deaths had occurred ( 13 in the ICD group and 17 in the control group ) . Cumulative survival was not significantly different between the two groups ( 93 % and 80 % in the control group versus 92 % and 86 % in the ICD group after 2 and 4 years , respectively ) . Conclusions —This trial did not provide evidence in favor of prophylactic ICD implantation in patients with DCM of recent onset and impaired left ventricular ejection fraction BACKGROUND Leads in and on the heart of the transvenous implantable cardioverter defibrillator ( ICD ) form the Achilles ' heel of this system due to potential for peri- and postimplant complications . The S-ICD is a newer generation of the ICD that does not require leads on the heart or in the vasculature . We present the rationale and study design of the Evaluation oF FactORs ImpacTing CLinical Outcome and Cost EffectiveneSS of the S-ICD ( EFFORTLESS S-ICD ) Registry which was design ed to evaluate the long-term performance of the S-ICD including patient quality of life and long-term re source utilization . METHODS The Registry is an observational , nonr and omized , st and ard of care evaluation to be conducted at approximately 50 investigational centers in Europe and New Zeal and where the S-ICD is approved for use and distribution . Clinical Registry endpoints include perioperative ( 30 days postimplant ) complication-free rate , 360-day complication-free rate , and percentage of inappropriate shocks for atrial fibrillation and supraventricular ventricular tachyarrhythmia . Other endpoints include patient-reported outcomes ( e.g. , quality of life ) and hospital personnel implant and follow-up experience with the S-ICD system . CONCLUSIONS Results from EFFORTLESS will build on and exp and the initial published experience with the S-ICD , which demonstrated that the device successfully and consistently detects and treats episodes of sustained ventricular tachyarrhythmias . The Registry will also evaluate the patients ' perspective of how it is to live with an S-ICD as compared to a contemporary transvenous system and track the experience of implanting physicians and personnel performing patient follow-up with a completely subcutaneous system OBJECTIVES The purpose of this study was to determine the efficacy of implantable cardiac defibrillator ( ICD ) therapy in preventing sudden cardiac death ( SCD ) in post-infa rct ion patients with advanced left ventricular ( LV ) dysfunction . BACKGROUND The Multicenter Automatic Defibrillator Implantation Trial ( MADIT-II ) r and omized 1,232 post-infa rct ion patients with an ejection fraction of < or = 30 % to ICD or conventional therapy . In the ICD group , there was a 31 % decrease in the risk of total mortality . However , a better underst and ing of the mode of death is desirable in order to refine therapeutic interventions in high-risk population s. METHODS We evaluated the 202 deaths , using a variation of the Hinkle-Thaler classification system as well as a clinical classification system to determine the incidence of SCD and the incidence of cardiac death due to progressive LV failure . RESULTS The SCD rates were 10.0 % in the conventional group and 3.8 % in the ICD group ( p < 0.01 ) . The hazard ratio for the risk of SCD in the ICD group compared with the conventional therapy group was 0.33 ( 95 % confidence interval 0.20 to 0.53 , p < 0.0001 ) . The ICD had no meaningful effect on non-sudden death ( p = 0.32 ) . The effect of defibrillator therapy in reducing SCD was similar in subgroup analyses stratified according to relevant baseline characteristics . CONCLUSIONS The decrease in mortality with ICD therapy in MADIT-II is entirely due to a reduction in SCD , with similar reductions in SCD in a spectrum of subgroups stratified according to relevant baseline characteristics Background —Three r and omized clinical trials showed that implantable cardioverter-defibrillators ( ICDs ) reduce the risk of death in survivors of ventricular tachyarrhythmias , but the cost per year of life gained is high . A sub study of the Canadian Implantable Defibrillator Study ( CIDS ) showed that 3 clinical factors , age ≥70 years , left ventricular ejection fraction ≤35 % , and New York Heart Association class III , predicted the risk of death and benefit from the ICD . We estimated the extent to which selecting patients for ICD therapy based on these risk factors makes ICD therapy more economically attractive . Methods and Results — Patients in CIDS were grouped according to whether they had ≥2 of 3 risk factors . Incremental cost-effectiveness of ICD therapy was computed as the ratio of the difference in mean cost to the difference in life expectancy between the 2 groups . Over 6.3 years , the mean cost per patient in the ICD group was Canadian ( C ) $ 87 715 versus $ 38 600 in the amiodarone group ( C$ 1≈US$0.67 ) . Life expectancy for the ICD group was 4.58 years versus 4.35 years for amiodarone , for an incremental cost-effectiveness of ICD therapy of C$ 213 543 per life-year gained . The cost per life-year gained in patients with ≥2 factors was C$ 65 195 , compared with C$ 916 659 with < 2 risk factors . Conclusions —The cost-effectiveness of ICD therapy varies by patient risk factor status . The use of ICD therapy in patients who have ≥2 risk factors of age ≥70 years , left ventricular ejection fraction ≤35 % , and NYHA class III is C$ 65 195 to gain a year of life AIMS The CArdiac REsynchronization-Heart Failure study r and omized patients with left ventricular ejection fraction < or = 35 % , markers of cardiac dyssynchrony , and persistent moderate or severe symptoms of heart failure despite pharmacological therapy , to implantation of a cardiac resynchronization therapy ( CRT ) device or not . The main study observed substantial benefits on morbidity and mortality during a mean follow-up of 29.4 months [ median 29.6 , interquartile range ( IQR ) 23.6 - 34.6 ] . Prior to study closure , an extension phase lasting a further 8 months ( allowing time for data analysis and presentation ) was declared during which cross-over was discouraged . METHODS AND RESULTS This was an extension of the already reported open-label r and omized trial described above . The primary outcome of the extension phase was all-cause mortality from the time of r and omization to completion of the extension phase . The secondary outcome was mode of death . The mean follow-up was 37.4 months ( median 37.6 , IQR 31.5 - 42.5 , range 26.1 - 52.6 months ) . There were 154 deaths ( 38.1 % ) in 404 patients assigned to medical therapy and 101 deaths ( 24.7 % ) in 409 patients assigned to CRT ( hazard ratio 0.60 , 95 % CI 0.47 - 0.77 , P<0.0001 ) without evidence of heterogeneity in pre-specified subgroups . A reduction in the risk of death due to heart failure ( 64 vs. 38 deaths ; hazard ratio 0.55 , 95 % CI 0.37 - 0.82 , P=0.003 ) and sudden death was observed ( 55 vs. 32 ; hazard ratio 0.54 , 95 % CI 0.35 - 0.84 , P=0.005 ) . CONCLUSION The benefits of CRT observed in the main trial persist or increase with longer follow-up . Reduction in mortality was due to fewer deaths both from worsening heart failure and from sudden death BACKGROUND Cardiac resynchronization reduces symptoms and improves left ventricular function in many patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony . We evaluated its effects on morbidity and mortality . METHODS Patients with New York Heart Association class III or IV heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony who were receiving st and ard pharmacologic therapy were r and omly assigned to receive medical therapy alone or with cardiac resynchronization . The primary end point was the time to death from any cause or an unplanned hospitalization for a major cardiovascular event . The principal secondary end point was death from any cause . RESULTS A total of 813 patients were enrolled and followed for a mean of 29.4 months . The primary end point was reached by 159 patients in the cardiac-resynchronization group , as compared with 224 patients in the medical-therapy group ( 39 percent vs. 55 percent ; hazard ratio , 0.63 ; 95 percent confidence interval , 0.51 to 0.77 ; P<0.001 ) . There were 82 deaths in the cardiac-resynchronization group , as compared with 120 in the medical-therapy group ( 20 percent vs. 30 percent ; hazard ratio 0.64 ; 95 percent confidence interval , 0.48 to 0.85 ; P<0.002 ) . As compared with medical therapy , cardiac resynchronization reduced the interventricular mechanical delay , the end-systolic volume index , and the area of the mitral regurgitant jet ; increased the left ventricular ejection fraction ; and improved symptoms and the quality of life ( P<0.01 for all comparisons ) . CONCLUSIONS In patients with heart failure and cardiac dyssynchrony , cardiac resynchronization improves symptoms and the quality of life and reduces complications and the risk of death . These benefits are in addition to those afforded by st and ard pharmacologic therapy . The implantation of a cardiac-resynchronization device should routinely be considered in such patients BACKGROUND Patients with nonischemic dilated cardiomyopathy are at substantial risk for sudden death from cardiac causes . However , the value of prophylactic implantation of an implantable cardioverter-defibrillator ( ICD ) to prevent sudden death in such patients is unknown . METHODS We enrolled 458 patients with nonischemic dilated cardiomyopathy , a left ventricular ejection fraction of less than 36 percent , and premature ventricular complexes or nonsustained ventricular tachycardia . A total of 229 patients were r and omly assigned to receive st and ard medical therapy , and 229 to receive st and ard medical therapy plus a single-chamber ICD . RESULTS Patients were followed for a mean ( + /-SD ) of 29.0+/-14.4 months . The mean left ventricular ejection fraction was 21 percent . The vast majority of patients were treated with angiotensin-converting-enzyme ( ACE ) inhibitors ( 86 percent ) and beta-blockers ( 85 percent ) . There were 68 deaths : 28 in the ICD group , as compared with 40 in the st and ard-therapy group ( hazard ratio , 0.65 ; 95 percent confidence interval , 0.40 to 1.06 ; P=0.08 ) . The mortality rate at two years was 14.1 percent in the st and ard-therapy group ( annual mortality rate , 7 percent ) and 7.9 percent in the ICD group . There were 17 sudden deaths from arrhythmia : 3 in the ICD group , as compared with 14 in the st and ard-therapy group ( hazard ratio , 0.20 ; 95 percent confidence interval , 0.06 to 0.71 ; P=0.006 ) . CONCLUSIONS In patients with severe , nonischemic dilated cardiomyopathy who were treated with ACE inhibitors and beta-blockers , the implantation of a cardioverter-defibrillator significantly reduced the risk of sudden death from arrhythmia and was associated with a nonsignificant reduction in the risk of death from any cause Background —The effects of cardiac resynchronization therapy ( CRT ) in patients with mildly symptomatic heart failure have not been fully eluci date d. Methods and Results —The Multicenter InSync ICD R and omized Clinical Evaluation II ( MIRACLE ICD II ) was a r and omized , double-blind , parallel-controlled clinical trial of CRT in NYHA class II heart failure patients on optimal medical therapy with a left ventricular ( LV ) ejection fraction ≤35 % , a QRS ≥130 ms , and a class I indication for an ICD . One hundred eighty-six patients were r and omized : 101 to the control group ( ICD activated , CRT off ) and 85 to the CRT group ( ICD activated , CRT on ) . End points included peak & OV0312;o2 , & OV0312;e/&OV0312;co2 , NYHA class , quality of life , 6-minute walk distance , LV volumes and ejection fraction , and composite clinical response . Compared with the control group at 6 months , no significant improvement was noted in peak & OV0312;o2 , yet there were significant improvements in ventricular remodeling indexes , specifically LV diastolic and systolic volumes ( P=0.04 and P=0.01 , respectively ) , and LV ejection fraction ( P=0.02 ) . CRT patients showed statistically significant improvement in & OV0312;e/&OV0312;co2 ( P=0.01 ) , NYHA class ( P=0.05 ) , and clinical composite response ( P=0.01 ) . No significant differences were noted in 6-minute walk distance or quality of life scores . Conclusions —In patients with mild heart failure symptoms on optimal medical therapy with a wide QRS complex and an ICD indication , CRT did not alter exercise capacity but did result in significant improvement in cardiac structure and function and composite clinical response over 6 months CONTEXT Cardiac resynchronization therapy ( CRT ) through biventricular pacing is an effective treatment for heart failure ( HF ) with a wide QRS ; however , the outcomes of patients requiring CRT and implantable cardioverter defibrillator ( ICD ) therapy are unknown . OBJECTIVE To examine the efficacy and safety of combined CRT and ICD therapy in patients with New York Heart Association ( NYHA ) class III or IV congestive HF despite appropriate medical management . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , parallel-controlled trial conducted from October 1 , 1999 , to August 31 , 2001 , of 369 patients with left ventricular ejection fraction of 35 % or less , QRS duration of 130 ms , at high risk of life-threatening ventricular arrhythmias , and in NYHA class III ( n = 328 ) or IV ( n = 41 ) despite optimized medical treatment . INTERVENTIONS Of 369 r and omized patients who received devices with combined CRT and ICD capabilities , 182 were controls ( ICD activated , CRT off ) and 187 were in the CRT group ( ICD activated , CRT on ) . MAIN OUTCOME MEASURES The primary double-blind study end points were changes between baseline and 6 months in quality of life , functional class , and distance covered during a 6-minute walk . Additional outcome measures included changes in exercise capacity , plasma neurohormones , left ventricular function , and overall HF status . Survival , incidence of ventricular arrhythmias , and rates of hospitalization were also compared . RESULTS At 6 months , patients assigned to CRT had a greater improvement in median ( 95 % confidence interval ) quality of life score ( -17.5 [ -21 to -14 ] vs -11.0 [ -16 to -7 ] , P = .02 ) and functional class ( -1 [ -1 to -1 ] vs 0 [ -1 to 0 ] , P = .007 ) than controls but were no different in the change in distance walked in 6 minutes ( 55 m [ 44 - 79 ] vs 53 m [ 43 - 75 ] , P = .36 ) . Peak oxygen consumption increased by 1.1 mL/kg per minute ( 0.7 - 1.6 ) in the CRT group vs 0.1 mL/kg per minute ( -0.1 to 0.8 ) in controls ( P = .04 ) , although treadmill exercise duration increased by 56 seconds ( 30 - 79 ) in the CRT group and decreased by 11 seconds ( -55 to 12 ) in controls ( P<.001 ) . No significant differences were observed in changes in left ventricular size or function , overall HF status , survival , and rates of hospitalization . No proarrhythmia was observed and arrhythmia termination capabilities were not impaired . CONCLUSIONS Cardiac resynchronization improved quality of life , functional status , and exercise capacity in patients with moderate to severe HF , a wide QRS interval , and life-threatening arrhythmias . These improvements occurred in the context of underlying appropriate medical management without proarrhythmia or compromised ICD function Context Using biventricular pacemakers to resynchronize ventricular contraction improves outcomes of heart failure in some patients . The cost-effectiveness of cardiac resynchronization is unknown . Contribution This Markov model estimates that , compared with medical therapy , cardiac resynchronization cost about $ 107800 per quality -adjusted life-year saved . Caution s While the cost-effectiveness of cardiac resynchronization is in the general range of other commonly used interventions , the estimates depended strongly on the authors ' assumptions about mortality and hospitalization rates after cardiac resynchronization . The Editors Congestive heart failure is a common , costly , and debilitating illness . It affects an estimated 4.8 million patients in the United States , and 400000 new cases are identified every year ( 1 ) . Approximately 30 % to 50 % of patients with heart failure have major intraventricular conduction delay , which is associated with higher risk for adverse events ( 2 , 3 ) . Biventricular pacemakers resynchronize the ventricular contraction to improve ejection fraction and relaxation of the left ventricle ( 4 ) . However , not all therapies that improve functional outcomes in patients with heart failure reduce mortality ( 5 ) . The long-term mortality , morbidity , and costs associated with cardiac resynchronization therapy remain unclear . Economic evaluation of an intervention assesses its effectiveness and costs so that decision makers can decide whether it is good value for the money . If cardiac resynchronization is effective and inexpensive , then the lives of thous and s will be improved annually . If not , then limited health care re sources can be invested in other interventions that are better value for the money . We used decision analysis to estimate the incremental cost-effectiveness of cardiac resynchronization therapy versus medical therapy . Methods Our target population was patients with reduced ventricular function and prolonged QRS . The decision model compared the lifetime effects and costs of cardiac resynchronization therapy and medical therapy in patients with congestive heart failure . We made the following assumptions about the costs and effects of cardiac resynchronization . Unit costs of complications related to cardiac resynchronization were identical to those for implantable cardioverter defibrillators , since the costs of insertion of either device were similar ( Table 1 ) ( 10 ) . Unit costs of heart failure therapy ( that is , costs of outpatient or inpatient care ) were otherwise identical for medical therapy and cardiac resynchronization . The incidence of complications associated with cardiac resynchronization was constant over time from implantation . Any mechanical malfunction of the device required battery replacement , with consequent costs and consequences . Uncomplicated cardiac resynchronization and medical therapy yielded identical health-related quality of life . The utility for hospitalization was identical for both therapies regardless of the reason for hospitalization . We incorporated the morbidity of hospitalization into the model by assigning the utility for hospitalization to its duration and assigning the utility for the health state before hospitalization to the remainder of the cycle . Finally , age-specific mortality due to unrelated causes was based on life tables ( 11 ) . Structure of the Decision Model The base-case analysis considered patients with New York Heart Association ( NYHA ) class III heart failure . The analysis considered the lifetime horizon , as recommended elsewhere ( 12 ) . A state-transition Markov model compared costs and outcomes of congestive heart failure treated with cardiac resynchronization therapy versus medical therapy . A cycle length of 1 month was used . During each cycle , patients who received medical therapy could die , be hospitalized for heart failure , or remain stable ( Figure 1 ) . Patients who underwent insertion of a device capable of cardiac resynchronization could die during the initial implantation ; experience lead infection , lead failure , and battery failure ; or experience any of the health states associated with medical therapy for heart failure ( Figure 2 ) . Figure 1 . Markov model of medical therapy for heart failure . Figure 2 . Markov model of cardiac resynchronization therapy ( CRT ) for heart failure . The reference-case analysis considered only the effect of resynchronization on all-cause mortality , since it is difficult to subclassify causes of death in patients with cardiovascular disease ( 13 ) . The concurrent systematic review ( 14 ) considered death due to any cause , cardiac death , and sudden cardiac death separately . However , the pooled relative risk for cardiac death and sudden cardiac death was based on retrospective subgroup analyses of data observed in the r and omized trials of cardiac resynchronization therapy . Such post hoc determinations may be susceptible to bias . Therefore , cardiac and noncardiac death were considered only in secondary economic analyses that accounted for patient age at implantation ( that is , differences in mortality due to unrelated causes ) . Decision analyses were performed by using DATA Pro ( TreeAge Software , Inc. , Williamstown , Massachusetts ) and Excel 2000 ( Microsoft Corp. , Redmond , Washington ) . Statistical analyses were performed with S-PLUS ( Insightful Corp. , Seattle , Washington ) . Input Data Survival and Hospitalization We obtained the probabilities of cardiovascular death , arrhythmic death , death from heart failure , hospitalization for heart failure , and adverse effects associated with either therapy from a concurrent systematic review ( 14 ) . Nine trials were included in the efficacy analysis : a study from the Multisite Stimulation in Cardiomyopathies ( MUSTIC ) Study Investigators examining sinus rhythm ( 4 ) ; a study from the MUSTIC Study Investigators examining atrial fibrillation ( 15 ) ; a trial by Garrigue and colleagues ( 16 ) ; the Pacing Therapies for Congestive Heart Failure ( PATH-CHF ) trial ( 17 ) ; a trial examining the safety and effectiveness of the Guidant Cardiac Resynchronization Therapy Defibrillator System ( CONTAK-CD ) ( 18 ) ; the Multicenter InSync R and omized Clinical Evaluation ( MIRACLE ) ( 19 , 20 ) ; the Multicenter InSync R and omized Clinical Evaluation Implantable Cardioverter Defibrillator ( MIRACLE-ICD ) ( 21 ) ; the Comparison of Medical Therapy , Pacing and Defibrillation in Chronic Heart Failure ( COMPANION ) ( 22 ) ; and 1 trial that remains unpublished ( Leclercq C , Alonso F , d'Allones FR , et al. Effets moyen terme de la stimulation multisite biventriculaire dans l'insuffisance cardiaque svre . Personal communication . May 2003 ) . We annualized the rate of events observed among patients r and omly assigned to medical therapy by using an exponential approximation ( 23 , 24 ) . Transition probabilities incorporated into the Markov model were adjusted for the cycle length . Pooled relative risks were calculated by using fixed-effects methods ( 25 ) . Quality of Life We estimated the health-related quality of life of patients with heart failure by eliciting utilities ( Appendix ) , since current st and ards suggest that use of such outcome measures ( 7 ) and the relative cost-effectiveness of some cardiac therapies are sensitive to the difference between the utilities associated with either treatment ( 8) . The general public was surveyed because the analysis considered re source allocation among different types of interventions ( that is , medical therapy vs. resynchronization ) rather than allocation for a single intervention ( 7 ) . Costs The economic analysis was conducted from a health care perspective , including costs of hospitalization , procedures , and laboratory tests . Costs were expressed in 2003 U.S. dollars ( Table 1 ) . The costs of insertion of a resynchronization-capable device were based on a survey of manufacturers ' list prices . Physician costs related to cardiac resynchronization were based on Current Procedural Terminology codes ( 26 ) . The costs of hospitalizations associated with congestive heart failure were based on estimates derived from a cohort study of health re source use by patients participating in a previous r and omized trial of medical therapy for heart failure ( 9 ) . All costs were adjusted for inflation by using the U.S. Consumer Price Indexes ( 27 ) . Table 1 . Input Data Uncertainty and Variability Analyses The analysis distinguished between parameter uncertainty ( that is , variation in costs and effects due to sampling and measurement error ) and variability ( that is , heterogeneity in costs and effects between groups of patients with systematic differences in cost or effects ) . Uncertainty was assessed by using 10000 probabilistic Monte Carlo simulations ( 28 , 29 ) . Empirical cost variables were assigned log-normal distributions , and empirical probability variables were assigned distributions ( 28 ) . Variables without a known distributional form ( that is , those with assumed values or those with values based on a range of published reports ) were assigned triangular distributions ( 30 ) . Since there is no absolute cost-effectiveness criterion ( 31 ) , the results of the Monte Carlo simulation were illustrated as a scatter plot of incremental effects in quality -adjusted life-years ( QALYs ) versus incremental costs . In such a plot , the incremental cost-effectiveness ratio is represented by the slope of incremental costs to incremental effects . The uncertainty in costs and effects was also illustrated as a cost-effectiveness acceptability curve ( 32 - 34 ) . An acceptability curve is a conditional probability plot showing the proportion of the observed incremental cost-effectiveness density that lies below a threshold ratio ( ) , which represents the monetary value of a QALY . The plot is conditional on , and therefore the decision maker can interpret the data relative to the threshold willingness to pay for the incremental health outcome . Variability was assessed by using sensitivity analyses . We replaced the value of each variable in the decision model with its BACKGROUND Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure ( CHF ) . Treatment with amiodarone or an implantable cardioverter-defibrillator ( ICD ) has been proposed to improve the prognosis in such patients . METHODS We r and omly assigned 2521 patients with New York Heart Association ( NYHA ) class II or III CHF and a left ventricular ejection fraction ( LVEF ) of 35 percent or less to conventional therapy for CHF plus placebo ( 847 patients ) , conventional therapy plus amiodarone ( 845 patients ) , or conventional therapy plus a conservatively programmed , shock-only , single-lead ICD ( 829 patients ) . Placebo and amiodarone were administered in a double-blind fashion . The primary end point was death from any cause . RESULTS The median LVEF in patients was 25 percent ; 70 percent were in NYHA class II , and 30 percent were in class III CHF . The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent . The median follow-up was 45.5 months . There were 244 deaths ( 29 percent ) in the placebo group , 240 ( 28 percent ) in the amiodarone group , and 182 ( 22 percent ) in the ICD group . As compared with placebo , amiodarone was associated with a similar risk of death ( hazard ratio , 1.06 ; 97.5 percent confidence interval , 0.86 to 1.30 ; P=0.53 ) and ICD therapy was associated with a decreased risk of death of 23 percent ( 0.77 ; 97.5 percent confidence interval , 0.62 to 0.96 ; P=0.007 ) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population . Results did not vary according to either ischemic or nonischemic causes of CHF , but they did vary according to the NYHA class . CONCLUSIONS In patients with NYHA class II or III CHF and LVEF of 35 percent or less , amiodarone has no favorable effect on survival , whereas single-lead , shock-only ICD therapy reduces overall mortality by 23 percent BACKGROUND This trial was design ed to determine whether cardiac-resynchronization therapy ( CRT ) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms , a reduced ejection fraction , and a wide QRS complex . METHODS During a 4.5-year period , we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy , an ejection fraction of 30 % or less , a QRS duration of 130 msec or more , and New York Heart Association class I or II symptoms . Patients were r and omly assigned in a 3:2 ratio to receive CRT plus an implantable cardioverter-defibrillator ( ICD ) ( 1089 patients ) or an ICD alone ( 731 patients ) . The primary end point was death from any cause or a nonfatal heart-failure event ( whichever came first ) . Heart-failure events were diagnosed by physicians who were aware of the treatment assignments , but they were adjudicated by a committee that was unaware of assignments . RESULTS During an average follow-up of 2.4 years , the primary end point occurred in 187 of 1089 patients in the CRT-ICD group ( 17.2 % ) and 185 of 731 patients in the ICD-only group ( 25.3 % ) ( hazard ratio in the CRT-ICD group , 0.66 ; 95 % confidence interval [ CI ] , 0.52 to 0.84 ; P=0.001 ) . The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy . The superiority of CRT was driven by a 41 % reduction in the risk of heart-failure events , a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more . CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction . There was no significant difference between the two groups in the overall risk of death , with a 3 % annual mortality rate in each treatment group . Serious adverse events were infrequent in the two groups . CONCLUSIONS CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex . ( Clinical Trials.gov number , NCT00180271 . OBJECTIVES We sought to compare the short- and long-term clinical effects of atrial synchronous pre-excitation of one ( univentricular ) or both ventricles ( biventricular ) , that provide cardiac resynchronization therapy ( CRT ) . BACKGROUND In patients with heart failure ( HF ) who have a ventricular conduction delay , CRT improves systolic hemodynamic function . The clinical benefit of CRT is still being investigated . METHODS Forty-one patients were r and omized to four weeks of first treatment with biventricular or univentricular stimulation , followed by four weeks without treatment , and then four weeks of a second treatment with the opposite stimulation . The best CRT stimulation was continued for nine months . Cardiac resynchronization therapy was optimized by hemodynamic testing at implantation . The primary end points were exercise capacity measures . Data were analyzed by two-way repeated- measures analysis of variance . RESULTS The left ventricle was selected for univentricular pacing in 36 patients . The clinical effects of univentricular and biventricular CRT were not significantly different . The results of each method were pooled to assess sequential treatment effects . Oxygen uptake during bicycle exercise increased from 9.48 to 10.4 ml/kg/min at the anaerobic threshold ( p = 0.03 ) and from 12.5 to 14.3 ml/kg/min at peak exercise ( p < 0.001 ) with the first treatment , and from 10.0 to 10.7 ml/kg/min at the anaerobic threshold ( p = 0.2 ) and from 13.4 to 15.2 ml/kg/min at peak exercise ( p = 0.002 ) with the second treatment . The 6-min walk distance increased from 342 m at baseline to 386 m after the first treatment ( p < 0.001 ) and to 416 m after the second treatment ( p = 0.03 ) . All improvements persisted after 12 months of therapy . CONCLUSIONS Cardiac resynchronization therapy produces a long-term improvement in the clinical symptoms of patients with HF who have a ventricular conduction delay . The differences between optimized biventricular and univentricular therapy appear to be small for short-term treatment BACKGROUND Patients with left ventricular dysfunction who undergo coronary artery bypass graft ( CABG ) surgery frequently have late sudden cardiac death . The CABG Patch Trial is a prospect i ve , r and omized , multicenter clinical trial that r and omized patients at high risk at the completion of CABG surgery to implantation of an epicardial implantable cardioverter defibrillator ( ICD ) or to no antiarrhythmic treatment . The trial was design ed to determine whether prophylactic implantation of an ICD at the time of CABG surgery would result in a lower total mortality in long-term follow-up . METHODS Patients undergoing CABG surgery were eligible for the trial if they were younger than 80 years , had a left ventricular ejection fraction less than 0.36 , and had an abnormal signal averaged electrocardiogram . Patients with a history of sustained ventricular tachycardia or ventricular fibrillation were excluded from the trial . All patients were scheduled to undergo follow-up at 3-month intervals until 42 months after surgery . RESULTS R and omization of patients in the trial ended in February 1996 . During the recruitment period 71,855 patients were screened , 1,422 were eligible , 1,055 were enrolled ( signed consent forms ) , and 900 patients ( 76 % of eligible patients ) were r and omized . The mean age of the 446 patients in the ICD group was 64 years versus 63 years for the 454 patients in the control group . A total of 87 % of the participants in the ICD group were men versus 82 % in the control group ( p = NS ) . Most of the patients had a history of hypertension ( 55 % ) , smoking ( 78 % ) , and hypercholesterolemia ( 54 % ) . Half of the patients had clinical heart failure , and the mean ejection fraction for both patient groups was 0.27 + /- 0.06 . No difference was seen in the history of myocardial infa rct ion ( 83 % ) , congestive heart failure ( 50 % ) , or atrial ( 11 % ) or ventricular ( 17 % ) arrhythmias between the two groups . Major clinical characteristics ( age , sex , number of previous infa rct ions , incidence of heart failure , and mean left ventricular ejection fraction ) were almost identical to those found in another ICD primary prevention trial , the Multicenter Automatic Defibrillator Implantation Trial ( MADIT ) . CONCLUSIONS A high risk sample of patients was enrolled in The CABG Patch Trial , as shown by examination of their baseline characteristics AIMS This study investigates the 10-year survival in the ECHOES ( Echocardiographic Heart of Engl and Screening ) study and examines factors associated with prognosis . METHODS AND RESULTS A prospect i ve study was carried out to investigate 10-year survival in those with heart failure ( HF ) and /or left ventricular systolic dysfunction ( LVSD ) . The mean age of participants in ECHOES was 64 , and 50 % were male . Records of all 6162 screened participants were flagged , and deaths up to 25 February 2009 were coded . Causes of death were categorized according to diagnosis on death certificate . Kaplan-Meier curves and log rank tests were used to compare survival times of participants with HF and LVSD in different diagnostic groups . A Cox proportional hazards regression model was used to identify variables associated with risk of death . A total of 2062 of the 6162 ( 33.5 % ) participants had died at the census date in February 2009 . Of these deaths , 902 ( 43.7 % ) were due to cardiovascular disease , including 263 ( 12.8 % ) due to HF . Ten-year survival was 75 % for participants without HF , 26.7 % for those with HF , 37.6 % for those with LVSD , and 27.4 % for those with HF and LVSD . Multiple-cause HF had a 10-year survival of 11.6 % . Multiple variables including diabetes , valvular disease , diuretic use , and a previous label of HF , as well as lifestyle factors such as smoking and obesity , were associated with increased risk of death . CONCLUSIONS Patients with HF and LVSD have a poor prognosis . However , the mortality rates of all-cause , all-stage HF as measured in the ECHOES cohort are around half those reported for patients diagnosed for the first time with HF during hospital admission OBJECTIVES We sought to determine the effects of cardiac resynchronization therapy ( CRT ) in New York Heart Association ( NYHA ) functional class II heart failure ( HF ) and NYHA functional class I ( American College of Cardiology/American Heart Association stage C ) patients with previous HF symptoms . BACKGROUND Cardiac resynchronization therapy improves left ventricular ( LV ) structure and function and clinical outcomes in NYHA functional class III and IV HF with prolonged QRS . METHODS Six hundred ten patients with NYHA functional class I or II heart failure with a QRS > or = 120 ms and a LV ejection fraction < or = 40 % received a CRT device ( + /-defibrillator ) and were r and omly assigned to active CRT ( CRT-ON ; n = 419 ) or control ( CRT-OFF ; n = 191 ) for 12 months . The primary end point was the HF clinical composite response , which scores patients as improved , unchanged , or worsened . The prospect ively powered secondary end point was LV end-systolic volume index . Hospitalization for worsening HF was evaluated in a prospect i ve secondary analysis of health care use . RESULTS The HF clinical composite response end point , which compared only the percent worsened , indicated 16 % worsened in CRT-ON compared with 21 % in CRT-OFF ( p = 0.10 ) . Patients assigned to CRT-ON experienced a greater improvement in LV end-systolic volume index ( -18.4 + /- 29.5 ml/m2 vs. -1.3 + /- 23.4 ml/m2 , p < 0.0001 ) and other measures of LV remodeling . Time-to-first HF hospitalization was significantly delayed in CRT-ON ( hazard ratio : 0.47 , p = 0.03 ) . CONCLUSIONS The REVERSE ( REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction ) trial demonstrates that CRT , in combination with optimal medical therapy ( + /-defibrillator ) , reduces the risk for heart failure hospitalization and improves ventricular structure and function in NYHA functional class II and NYHA functional class I ( American College of Cardiology/American Heart Association stage C ) patients with previous HF symptoms . ( REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [ REVERSE ] ; NCT00271154 ) The Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation ( DEFINITE ) is a multicenter r and omized trial . Patients will have nonischemic cardiomyopathy ( LVEF < or = 35 % ) , a history of symptomatic heart failure and spontaneous arrhythmia ( > 10 PVCs/hour or nonsustained ventricular tachycardia defined as 3 - 15 beats at a rate of > 120 beats/min ) on Holter monitor or telemetry within the past 6 months . Patients will be r and omized to an implantable cardioverter defibrillator ( ICD ) versus no ICD . All patients will receive st and ard oral medical therapy for heart failure including angiotensin converting enzyme inhibitors and beta-blockers ( if tolerated ) . Patients will be followed for 2 - 3 years . The primary endpoint will be total mortality . Quality -of-life and pharmacoeconomics analyses will also be performed . A registry will track patients who meet basic inclusion criteria but are not r and omized . We estimate an annual total mortality of 15 % at 2 years in the treatment arm that does not receive an ICD . The ICD is expected to reduce mortality by 50 % . Approximately 204 patients will be required in each treatment group . Twenty-five centers will be included in a trial design ed to last an estimated 4 years The Canadian Implantable Defibrillator Study ( CIDS ) is an on-going r and omized multicenter clinical trial that compares implantable cardioverter-defibrillator ( ICD ) therapy against amiodarone in patients with prior cardiac arrest or hemodynamically unstable ventricular tachycardia . Eligible patients are equally r and omized to receive or not receive an ICD as initial management . Those not receiving an ICD receive amiodarone . All patients are seen in follow-up every 6 months . The primary outcome event cluster is arrhythmic death or any other death occurring within 30 days of therapy initiation . Secondary outcomes are all-cause mortality and nonfatal occurrences of ventricular tachycardia or fibrillation . The goal of the study is to recruit 400 patients over 4 years . All patients will be followed to the end of the year . This will result in an 80 % chance of detecting a reduction in arrhythmic death of 58 % by ICD if such a difference in truth exists . Recruitment began in October 1990 and 184 patients have been enrolled to date In 1987 , the Cardiac Arrest Study Hamburg ( CASH ) , a prospect i ve , multicenter , r and omized controlled study , was started in survivors of sudden cardiac death result ing from documented ventricular tachyarrhythmias . Through December 1991 , 230 survivors ( 46 women , 184 men ; mean age 57 + /- 11 years ) of cardiac arrest caused by ventricular tachyarrhythmias were r and omly assigned to receive either oral propafenone ( 56 patients ) , amiodarone ( 56 patients ) , or metoprolol ( 59 patients ) or to have an implantable defibrillator ( 59 patients ) without concomitant antiarrhythmic drugs . The primary endpoint of the study was total mortality . In March 1992 , the propafenone arm of CASH was stopped because of excess mortality compared with the implantable defibrillator group . This article presents preliminary results of the comparison of implantable defibrillator therapy with propafenone therapy . A significantly higher incidence of total mortality , sudden death ( 12 % ) , and cardiac arrest recurrence or sudden death ( 23 % ) was found in the propafenone group compared with the implantable defibrillator-treated patients ( 0 % , p < 0.05 ) . It was concluded that , in survivors of cardiac arrest , propafenone treatment is less effective than implantable defibrillator treatment BACKGROUND One third of patients with chronic heart failure have electrocardiographic evidence of a major intraventricular conduction delay , which may worsen left ventricular systolic dysfunction through asynchronous ventricular contraction . Uncontrolled studies suggest that multisite biventricular pacing improves hemodynamics and well-being by reducing ventricular asynchrony . We assessed the clinical efficacy and safety of this new therapy . METHODS Sixty-seven patients with severe heart failure ( New York Heart Association class III ) due to chronic left ventricular systolic dysfunction , with normal sinus rhythm and a duration of the QRS interval of more than 150 msec , received transvenous atriobiventricular pacemakers ( with leads in one atrium and each ventricle ) . This single-blind , r and omized , controlled crossover study compared the responses of the patients during two periods : a three-month period of inactive pacing ( ventricular inhibited pacing at a basic rate of 40 bpm ) and a three-month period of active ( atriobiventricular ) pacing . The primary end point was the distance walked in six minutes ; the secondary end points were the quality of life as measured by question naire , peak oxygen consumption , hospitalizations related to heart failure , the patients ' treatment preference ( active vs. inactive pacing ) , and the mortality rate . RESULTS Nine patients were withdrawn from the study before r and omization , and 10 failed to complete both study periods . Thus , 48 patients completed both phases of the study . The mean distance walked in six minutes was 22 percent greater with active pacing ( 399+/-100 m vs. 326+/-134 m , P<0.001 ) , the quality -of-life score improved by 32 percent ( P<0.001 ) , peak oxygen uptake increased by 8 percent ( P<0.03 ) , hospitalizations were decreased by two thirds ( P<0.05 ) , and active pacing was preferred by 85 percent of the patients ( P<0.001 ) . CONCLUSIONS Although it is technically complex , atriobiventricular pacing significantly improves exercise tolerance and quality of life in patients with chronic heart failure and intraventricular conduction delay INTRODUCTION The implantable cardioverter defibrillator ( ICD ) is commonly used to treat patients with documented sustained ventricular tachycardia ( VT ) or ventricular fibrillation ( VF ) . Arrhythmia recurrence rates in these patients are high , but which patients will receive a therapy and the forms of arrhythmia recurrence ( VT or VF ) are poorly understood . METHODS AND RESULTS The therapy delivered by the ICD was examined in 449 patients r and omized to ICD therapy in the Antiarrhythmics Versus Implantable Defibrillators ( AVID ) Trial . Events triggering ICD shocks or antitachycardia pacing ( ATP ) were review ed for arrhythmia diagnosis , clinical symptoms , activity at the onset of the arrhythmia , and appropriateness and results of therapy . Both shock and ATP therapies were frequent by 2 years , with 68 % of patients receiving some therapy or having an arrhythmic death . An appropriate shock was delivered in 53 % of patients , and ATP was delivered in 68 % of patients who had ATP activated . The first arrhythmia treated in follow-up was diagnosed as VT ( 63 % ) , VF ( 13 % ) , supraventricular tachycardia ( 18 % ) , unknown arrhythmia ( 3 % ) , or due to ICD malfunction or inappropriate sensing ( 3 % ) . Acceleration of an arrhythmia by the ICD occurred in 8 % of patients who received any therapy . No physical activity consistently preceded arrhythmias , nor did any single clinical factor predict the symptoms of the arrhythmia . CONCLUSION Delivery of ICD therapy in AVID patients was common , primarily due to VT . Inappropriate ICD therapy occurred frequently . Use of ICD therapy as a surrogate endpoint for death in clinical trials should be avoided BACKGROUND Patients who survive life-threatening ventricular arrhythmias are at risk for recurrent arrhythmias . They can be treated with either an implantable cardioverter-defibrillator or antiarrhythmic drugs , but the relative efficacy of these two treatment strategies is unknown . METHODS To address this issue , we conducted a r and omized comparison of these two treatment strategies in patients who had been resuscitated from near-fatal ventricular fibrillation or who had undergone cardioversion from sustained ventricular tachycardia . Patients with ventricular tachycardia also had either syncope or other serious cardiac symptoms , along with a left ventricular ejection fraction of 0.40 or less . One group of patients was treated with implantation of a cardioverter-defibrillator ; the other received class III antiarrhythmic drugs , primarily amiodarone at empirically determined doses . Fifty-six clinical centers screened all patients who presented with ventricular tachycardia or ventricular fibrillation during a period of nearly four years . Of 1016 patients ( 45 percent of whom had ventricular fibrillation , and 55 percent ventricular tachycardia ) , 507 were r and omly assigned to treatment with implantable cardioverter-defibrillators and 509 to antiarrhythmic-drug therapy . The primary end point was overall mortality . RESULTS Follow-up was complete for 1013 patients ( 99.7 percent ) . Overall survival was greater with the implantable defibrillator , with unadjusted estimates of 89.3 percent , as compared with 82.3 percent in the antiarrhythmic-drug group at one year , 81.6 percent versus 74.7 percent at two years , and 75.4 percent versus 64.1 percent at three years ( P<0.02 ) . The corresponding reductions in mortality ( with 95 percent confidence limits ) with the implantable defibrillator were 39+/-20 percent , 27+/-21 percent , and 31+/-21 percent CONCLUSIONS Among survivors of ventricular fibrillation or sustained ventricular tachycardia causing severe symptoms , the implantable cardioverter-defibrillator is superior to antiarrhythmic drugs for increasing overall survival BACKGROUND One third of chronic heart failure patients have major intraventricular conduction and uncoordinated ventricular contraction . Non-controlled studies suggest that biventricular pacing may improve haemodynamics and well-being by reducing ventricular asynchrony . The aim of this trial was to assess the clinical efficacy and safety of this new therapy in patients with chronic atrial fibrillation . METHODS Fifty nine NYHA class III patients with left ventricular systolic dysfunction , chronic atrial fibrillation , slow ventricular rate necessitating permanent ventricular pacing , and a wide QRS complex ( paced width > or=200 ms ) , were implanted with transvenous biventricular-VVIR pacemakers . This single-blind , r and omized , controlled , crossover study compared the patients ' parameters , as monitored during two 3-month treatment periods of conventional right-univentricular vs biventricular pacing . The primary end-point was the 6-min walked distance , secondary end-points were peak oxygen uptake , quality -of-life , hospitalizations , patients ' preferred study period and mortality . RESULTS Because of a higher than expected drop-out rate ( 42 % ) , only 37 patients completed both crossover phases . In the intention-to-treat analysis , we did not observe a significant difference . However , in the patients with effective therapy the mean walked distance increased by 9.3 % with biventricular pacing ( 374+/-108 vs 342+/-103 m in univentricular;P = 0.05 ) . Peak oxygen uptake increased by 13 % ( P=0.04 ) . Hospitalizations decreased by 70 % and 85 % of the patients preferred the biventricular pacing period ( P<0.001 ) . CONCLUSION As compared with conventional VVIR pacing , effective biventricular pacing seems to improve exercise tolerance in NYHA class III heart failure patients with chronic atrial fibrillation and wide paced-QRS complexes . Further r and omized controlled studies are required to definitively vali date this therapy in such patients BACKGROUND The rate of death , including sudden cardiac death , is highest early after a myocardial infa rct ion . Yet current guidelines do not recommend the use of an implantable cardioverter-defibrillator ( ICD ) within 40 days after a myocardial infa rct ion for the prevention of sudden cardiac death . We tested the hypothesis that patients at increased risk who are treated early with an ICD will live longer than those who receive optimal medical therapy alone . METHODS This r and omized , prospect i ve , open-label , investigator-initiated , multicenter trial registered 62,944 unselected patients with myocardial infa rct ion . Of this total , 898 patients were enrolled 5 to 31 days after the event if they met certain clinical criteria : a reduced left ventricular ejection fraction ( < or = 40 % ) and a heart rate of 90 or more beats per minute on the first available electrocardiogram ( ECG ) ( criterion 1 : 602 patients ) , nonsustained ventricular tachycardia ( > or = 150 beats per minute ) during Holter monitoring ( criterion 2 : 208 patients ) , or both criteria ( 88 patients ) . Of the 898 patients , 445 were r and omly assigned to treatment with an ICD and 453 to medical therapy alone . RESULTS During a mean follow-up of 37 months , 233 patients died : 116 patients in the ICD group and 117 patients in the control group . Overall mortality was not reduced in the ICD group ( hazard ratio , 1.04 ; 95 % confidence interval [ CI ] , 0.81 to 1.35 ; P=0.78 ) . There were fewer sudden cardiac deaths in the ICD group than in the control group ( 27 vs. 60 ; hazard ratio , 0.55 ; 95 % CI , 0.31 to 1.00 ; P=0.049 ) , but the number of nonsudden cardiac deaths was higher ( 68 vs. 39 ; hazard ratio , 1.92 ; 95 % CI , 1.29 to 2.84 ; P=0.001 ) . Hazard ratios were similar among the three groups of patients categorized according to the enrollment criteria they met ( criterion 1 , criterion 2 , or both ) . CONCLUSIONS Prophylactic ICD therapy did not reduce overall mortality among patients with acute myocardial infa rct ion and clinical features that placed them at increased risk . ( Clinical Trials.gov number , NCT00157768 . BACKGROUND Patients with coronary heart disease , left ventricular dysfunction , and abnormalities on signal-averaged electrocardiograms have an increased risk sudden death . We evaluated the effect on survival of the prophylactic implantation of cardioverter-defibrillators in such patients at the time of coronary-artery bypass surgery . METHODS Over the course of five years , 37 clinical centers screened all patients who were scheduled for elective coronary bypass surgery . Patients were eligible for the trial if they were less than 80 years old , had a left ventricular ejection fraction of less than 0.36 , and had abnormalities on signal-averaged electrocardiograms . We identified 1422 eligible patients , enrolled 1055 , and r and omly assigned 900 to therapy with an implantable cardioverter-defibrillator ( 446 patients ) or to the control group ( 454 patients ) . The primary end point of the study was overall mortality , and the two groups were compared in an intention-to-treat analysis . RESULTS The base-line characteristics of the two groups were similar . During an average follow-up of 32+/-16 months , there were 101 deaths in the defibrillator group ( 71 from cardiac causes ) and 95 in the control group ( 72 from cardiac causes ) . The hazard ratio for death from any cause was 1.07 ( 95 percent confidence interval , 0.81 to 1.42 ; P=0.64 ) . There was no statistically significant interaction between defibrillator therapy and any of 10 preselected base-line covariates . CONCLUSIONS We found no evidence of improved survival among patients with coronary heart disease , a depressed left ventricular ejection fraction , and an abnormal signal-averaged electrocardiogram in whom a defibrillator was implanted prophylactically at the time of elective coronary bypass surgery Sudden cardiac death struck approximately 360 000 persons in the United States in 1990 [ 1 , 2 ] . Defined as death that occurs within 1 hour of the onset of symptoms , sudden cardiac death accounts for about one half of all deaths from heart disease [ 2 ] . Sudden cardiac death occurs primarily in patients who have an established history of heart disease , particularly those with a history of severe congestive heart failure , myocardial infa rct ion , or sustained ventricular arrhythmia [ 3 ] . The therapeutic alternatives are treatment with antiarrhythmic drugs or treatment with an implantable cardioverter defibrillator ( ICD ) [ 4 ] . Type Ia antiarrhythmic agents ( for example , procainamide ) were previously a mainstay of pharmacologic therapy , but recent evidence has raised concern about their effectiveness and potential toxicity [ 5 - 8 ] . In 1991 , it was found that the type Ic agents encainide and flecainide increased mortality when used to suppress ventricular ectopy after myocardial infa rct ion . This unexpected finding further limited the choice of antiarrhythmic drugs [ 9 ] . Amiodarone is one of the most promising pharmacologic alternatives [ 10 - 14 ] . However , amiodarone therapy is complicated by lengthy loading regimens ; persistence of the drug in adipose tissue for long periods ; and severe adverse effects , including pulmonary fibrosis and thyroid abnormalities [ 15 , 16 ] . With the development of ICDs that can be implanted without thoracotomy ( and possibly during an outpatient procedure ) , use of an ICD is now a practical therapeutic alternative to antiarrhythmic drug therapy [ 4 ] . Although ICDs are remarkably effective in terminating ventricular arrhythmias [ 17 - 20 ] , they are expensive ( $ 40 000 to $ 60 000 for implantation ) , and the extent to which they extend life is unknown [ 21 ] . Ongoing or planned r and omized , controlled trials [ 19 , 20 , 22 - 27 ] will clarify the role of ICDs and drug therapy for the prevention of sudden cardiac death , but their results will not be available for several years . Economic analyses have suggested that ICDs have favorable cost-effectiveness ratios [ 28 - 32 ] , but these analyses were based on controversial assumptions about efficacy in improving survival [ 28 , 30 , 31 ] ; compared the implantation of an ICD with an expensive alternative , such as electrophysiologically guided therapy [ 29 , 31 , 32 ] ; or limited the use of ICDs to extremely high-risk patients [ 28 - 32 ] . In this study , we used data from ongoing r and omized trials and data on the costs of third-generation ICDs to evaluate the cost-effectiveness of treatment with an ICD ( implanted without thoracotomy ) relative to empirical therapy with amiodarone . We determined the reduction in total mortality that ICD use would have to confer to reach specified cost-effectiveness ratios . Because the indications for ICD use may exp and the use of this therapy into new patient population s , we evaluated how the cost-effectiveness of treatment with an ICD varies when the device is used in a population that has a lower risk for sudden cardiac death than do survivors of cardiac arrest . Methods We used a decision model to estimate the quality -adjusted length of life and expenditures for a population of patients who received amiodarone or an ICD . We used the perspective of society and incorporated benefits and costs accordingly . We examined three treatment strategies ( Figure 1 ) . Patients who received the ICD-only regimen began treatment with an ICD and continued to receive this therapy regardless of subsequent arrhythmic events . Patients who received amiodarone only began treatment with amiodarone and continued to receive this drug as sole therapy regardless of subsequent arrhythmic events . They crossed over to receive an ICD only if they had intolerable side effects as a result of amiodarone use . Patients who received the amiodarone-to-ICD therapy began treatment with amiodarone and crossed over to ICD if they were subsequently resuscitated from ventricular fibrillation ( all survivors ) or from ventricular tachycardia ( 50 % of survivors ) or if severe drug toxicity occurred . We did not evaluate treatment strategies that used ICD and amiodarone simultaneously because evidence was not sufficient to assess the efficacy of this combined therapy . We discounted health benefits and costs using a 3 % annual discount rate , as recommended by a panel on cost-effectiveness analysis in health care [ 33 ] , and we did sensitivity analyses on all model variables . Figure 1 . Schematic representation of the decision model . Decision Model We developed a Markov model [ 34 , 35 ] ( Figure 1 , Appendix ) using SMLTree software ( version 2.9 , J. Hollenberg , New York , New York ) ; the model tracked a hypothetical cohort of patients over time . Each cohort began receiving one of the three therapeutic regimens : ICD only , amiodarone only , or amiodarone-to-ICD . Each month , a patient was at risk for ventricular fibrillation , ventricular tachycardia , nonarrhythmic cardiac death , noncardiac death , and illness or death from drug toxicity ( the latter was applicable only to patients who received amiodarone ) . Patients who had an ICD were also at risk for perioperative death . If a patient had ventricular fibrillation or ventricular tachycardia , the patient either died , survived with neurologic impairment , or survived without neurologic impairment ( Figure 2 ) . The model included a decrement in quality of life for patients who survived an arrhythmic event with neurologic sequelae [ 36 - 39 ] . Patients who were treated with amiodarone were at risk for acute drug toxicity ( Figure 2 ) . Figure 2 . Decision model subtrees . Top . Upper middle . Lower middle . Bottom . Quality of Life The Markov model incorporated adjustments for quality of life associated with current health , ICD or amiodarone therapy , arrhythmic events , ICD discharges ( shocks ) , and amiodarone toxicity . We used the time-tradeoff technique to calculate quality -adjusted life-years [ 40 , 41 ] . In the base-case analysis , we assumed that the quality of life of current health was 0.75 [ 39 ] , and we assumed that quality of life did not change as a result of ICD or amiodarone therapy . In sensitivity analyses , we evaluated the importance of changes in quality of life caused by ICD or amiodarone therapy . Effectiveness of Implantable Cardioverter Defibrillators We assumed that treatment with an ICD did not affect the frequency of arrhythmias but did increase the chance for surviving an arrhythmic event if one occurred . Evidence from r and omized trials and patient registries indicates that ICDs successfully treat life-threatening ventricular arrhythmias . In a registry that contained more than 600 patients with third-generation ICDs [ 17 ] , ventricular tachycardia was terminated successfully in 98.7 % of cases and ventricular fibrillation was converted in 98.9 % of cases . The Cardiac Arrest Survivors in Hamburg ( CASH ) study , a r and omized trial that compared ICD with pharmacologic therapy in survivors of cardiac arrest , reported a cardiac death rate of 0 % at 1 year among 59 patients treated with an ICD [ 16 , 19 , 20 , 42 ] . Other studies [ 18 , 43 - 46 ] have also reported low rates of sudden cardiac death in ICD recipients . In our base-case analysis , we assumed that ICDs successfully terminated arrhythmias at rates similar to those reported in the patient registry [ 17 ] ( Table 1 ) . Table 1 . Input Variables and Sources * The effect of ICD use on total mortality is less clear [ 67 - 70 ] . At approximately 1 year of follow-up , total mortality rates in the CASH study were 14.3 % in the group that received ICDs and 14.7 % in the group that received amiodarone ; the difference between the groups was not statistically significant [ 16 ] . However , this trial is incomplete and relatively small : Each treatment group contained fewer than 60 patients . In the Multicenter Automatic Defibrillator Implantation Trial ( MADIT ) , 196 patients who had a history of previous Q-wave infa rct ion , documented nonsustained ventricular tachycardia , an ejection fraction of 0.35 or less , and inducible sustained ventricular tachycardia ( shown on electrophysiologic testing ) that could not be suppressed by the infusion of procainamide were r and omly assigned to receive either an ICD or conventional pharmacologic care [ 25 ] . The trial was stopped early because 15 deaths occurred in the ICD group and 39 occurred in the usual care group , producing a hazard ratio for total mortality of 0.46 ( 95 % CI , 0.26 to 0.82 ) . This corresponds to Kaplan-Meier survival rates of 87 % in the ICD group and 65 % in the usual care group at approximately 2 years ( Moss AJ for the MADIT Investigators . Multicenter Automatic Implantable Defibrillator Trial [ MADIT ] . 17th Annual Scientific Session of the North American Society of Pacing and Electrophysiology . Seattle ; 1996 ) . The risk reduction found in MADIT may particularly favor ICD because selected patients were not suppressed by drug therapy and because the trial was discontinued early . Other large r and omized trials of ICD treatment are still ongoing and have not reported any results . Cost-effectiveness studies [ 28 , 30 , 31 ] ( with one exception [ 32 ] ) have assumed that patients who receive ICDs have substantial survival advantages . This assumption has been based on the results of nonr and omized trials , which are subject to selection bias because healthier patients may have had ICD implantation . Such bias precludes definitive inferences about the effect of ICDs on total mortality [ 21 , 71 ] . For our base-case analysis , therefore , we assumed that ICD use would reduce total mortality at 1 year by 20 % to 40 % relative to amiodarone therapy in patients who survive ICD implantation . This reduction was approximately constant over time . In sensitivity analyses , we examined reductions in total mortality by ICDs compared with amiodarone that varied from 5 % to 60 % . A reduction in total mortality of 30 % is a reasonable point estimate , given the current evidence . We assumed that the implantation of an ICD was associated with a perioperative mortality rate of 1 Background —An implantable cardioverter defibrillator ( ICD ) may be effective in reducing the risk of sudden cardiac death . The high cost of ICD treatment , however , compared with alternatives raises the question of whether this new technology is an efficient use of scarce health care re sources . Objective —To estimate the incremental cost effectiveness of the implantable cardioverter defibrillator compared with drug treatment with amiodarone in the management of patients at high risk of sudden cardiac death . Design —A cost effectiveness model was constructed from data already published and other secondary sources . Differences in patient survival were calculated from life tables for comparable ICD and amiodarone patient series . Costs were based on typical patient management protocol s derived from current United Kingdom practice and interviews with physicians . Main outcome measures —Cost effectiveness of ICD treatment was computed over 20 years ; all future costs and effects were discounted at 6 % per year . Results —Estimated life expectancy was 11·1 and 6·7 years with ICD and amiodarone respectively ; the discounted 20 year difference lies in the range 1·7 to 3·7 years . Discounted 20 year treatment costs were £ 28 400 for the ICD and £ 2300 for amiodarone . Cost effectiveness of ICD treatment lies in the range of £ 15 400 to £ 8200 per life-year gained . Conclusions —Cost effectiveness of ICD treatment is similar to some existing cardiac programmes funded under the NHS but uncertainty exists due to limitations of the data . Costs of ICD treatment may fall in the future as the life of the device increases and less invasive implantation methods are needed . The effectivess of ICD compared with amiodarone is currently being studied by a r and omised controlled trial Objective To test whether a drug review and symptom self management and lifestyle advice intervention by community pharmacists could reduce hospital admissions or mortality in heart failure patients . Design R and omised controlled trial . Setting Home based intervention in heart failure patients . Participants 293 patients diagnosed with heart failure were included ( 149 intervention , 144 control ) after an emergency admission . Intervention Two home visits by one of 17 community pharmacists within two and eight weeks of discharge . Pharmacists review ed drugs and gave symptom self management and lifestyle advice . Controls received usual care . Main outcome measures The primary outcome was total hospital readmissions at six months . Secondary outcomes included mortality and quality of life ( Minnesota living with heart failure question naire and EQ-5D ) . Results Primary outcome data were available for 291 participants ( 99 % ) . 136 ( 91 % ) intervention patients received one or two visits . 134 admissions occurred in the intervention group compared with 112 in the control group ( rate ratio=1.15 , 95 % confidence interval 0.89 to 1.48 ; P=0.28 , Poisson model ) . 30 intervention patients died compared with 24 controls ( hazard ratio=1.18 , 0.69 to 2.03 ; P=0.54 ) . Although EQ-5D scores favoured the intervention group , Minnesota living with heart failure question naire scores favoured controls ; neither difference was statistically significant . Conclusion This community pharmacist intervention did not lead to reductions in hospital admissions in contrast to those found in trials of specialist nurse led interventions in heart failure . Given that heart failure accounts for 5 % of hospital admissions , these results present a problem for policy makers who are faced with a shortage of specialist provision and have hoped that skilled community pharmacists could produce the same benefits . Trial registration number IS RCT N59427925 Sodium channel blockers and class III antiarrhythmic compounds , as well as beta blockers , have been used in preventing recurrences of sudden cardiac death . In recent years , implantable cardioverter-defibrillators ( ICDs ) have been used increasingly , but no data from r and omized trials comparing antiarrhythmic drug and ICD therapy have been reported in this setting . In 1987 , the Cardiac Arrest Study Hamburg ( CASH ) , a prospect i ve , r and omized trial , was initiated to compare metoprolol , amiodarone , propafenone , and ICD implantation in patients surviving sudden cardiac death due to documented ventricular tachycardia and /or ventricular fibrillation . The details of the study design and preliminary results are presented herein . The primary endpoint of the study is total mortality . The data review ed in March 1992 , representing a mean follow-up period of 11 months , indicated no significant differences among patients r and omized to metoprolol , amiodarone , and ICDs . However , there was a significantly higher total mortality and cardiac arrest recurrence in patients r and omized to propafenone compared with those r and omized to the ICD treatment limb . The study continues with the deletion of the propafenone treatment limb Biventricular ( BV ) pacing is under clinical investigation for the treatment of heart failure . Its impact on mortality is unknown . Patients with heart failure and ventricular tachyarrhythmias received an implantable cardioverter defibrillator with BV pacing capability . Patients were r and omized 1:1 to BV pacing or no pacing , then crossed over to the alternate mode after 3 months . All-cause mortality was measured in each arm up to the point of crossover . Fifteen of 222 patients died between implant and crossover . Five patients died while programmed to BV pacing and 19 died while programmed to no pacing . Survival in the BV pacing arm was 93 + /- 4 % versus 86 + /- 6 % in the no pacing arm ( P = 0.18 ) . In a patient population with symptomatic heart failure and ventricular arrhythmias , BV pacing does not appear to be associated with excess mortality . Larger and longer studies will be needed to determine if BV pacing confers a survival benefit AIMS To assess the impact of hospital type on implantable cardioverter defibrillation ( ICD ) prescription rates . METHODS AND RESULTS The Wessex Cardiothoracic Unit is a regional implanting centre serving eight district general hospitals ( DGHs ) . We audited all new ICD implants performed in our institution over 4 years . Hospitals implanting or referring patients elsewhere were excluded . We categorized patients into three different groups depending on local hospital type-regional centre ( one hospital ) , DGH with a device specialist ( one hospital ) , DGH without a device specialist ( two hospitals ) . For each hospital type , we assessed the overall implant rate based on local population . There were 459 new ICD implants ; of which 381 were included in the analysis . Implant rates were higher in areas whose local hospital was a regional centre ( 103/million/year ) , when compared with DGHs with ( 49/million/year ) or without a device specialist ( 48/million/year ) . This disparity was greatest with respect to coronary artery disease primary prevention indications-implant rates 29 , 14 , and 9/million/year , respectively . CONCLUSIONS ICD implant rates are affected by hospital type and are significantly higher in regional centres when compared with DGHs . To increase ICD implant rates , the widespread implementation of clinical pathways to identify prospect i ve primary prevention patients may be needed BACKGROUND Implantation of transvenous implantable cardioverter defibrillators ( ICDs ) by use of a nonthoracotomy approach has become routine therapy for survivors of life-threatening tachyarrhythmias . The purpose of this study was to identify and prospect ively characterize the frequency of lead- and ICD-related complications from the Antiarrhythmics versus Implantable Defibrillators ( AVID ) Trial . METHODS AND RESULTS Between June 1 , 1993 , and April 7 , 1997 , 539 patients received nonthoracotomy ICDs either as initial treatment assignment ( 477 ) or as crossover from medical management ( 62 ) . A total of 62 first complications occurred . The subclavian route of insertion result ed in more complications than the cephalic vein route , 46 of 339 ( 14 % ) versus 6 of 135 ( 4 % ) , P = .005 , as did the abdominal versus pectoral generator site , 31 of 238 ( 13 % ) versus 17 of 291 ( 6 % ) , P<.02 . Most dislodgements and system infections tended to occur in the 3 months after implantation , whereas lead fractures continued to occur throughout follow-up . Failure to use perioperative antibiotics was a predictor of system infection ( P = .001 ) . CONCLUSIONS These data suggest that cephalic vein access and pectoral generator site may result in fewer complications . The continued occurrence of lead fractures and the need for premature system revision supports the practice of close routine ICD system surveillance BACKGROUND Empirical antiarrhythmic therapy has not reduced mortality among patients with coronary artery disease and asymptomatic ventricular arrhythmias . Previous studies have suggested that antiarrhythmic therapy guided by electrophysiologic testing might reduce the risk of sudden death . METHODS We conducted a r and omized , controlled trial to test the hypothesis that electrophysiologically guided antiarrhythmic therapy would reduce the risk of sudden death among patients with coronary artery disease , a left ventricular ejection fraction of 40 percent or less , and asymptomatic , unsustained ventricular tachycardia . Patients in whom sustained ventricular tachyarrhythmias were induced by programmed stimulation were r and omly assigned to receive either antiarrhythmic therapy , including drugs and implantable defibrillators , as indicated by the results of electrophysiologic testing , or no antiarrhythmic therapy . Angiotensin-converting-enzyme inhibitors and beta-adrenergic-blocking agents were administered if the patients could tolerate them . RESULTS A total of 704 patients with inducible , sustained ventricular tachyarrhythmias were r and omly assigned to treatment groups . Five-year Kaplan-Meier estimates of the incidence of the primary end point of cardiac arrest or death from arrhythmia were 25 percent among those receiving electrophysiologically guided therapy and 32 percent among the patients assigned to no antiarrhythmic therapy ( relative risk , 0.73 ; 95 percent confidence interval , 0.53 to 0.99 ) , representing a reduction in risk of 27 percent ) . The five-year estimates of overall mortality were 42 percent and 48 percent , respectively ( relative risk , 0.80 ; 95 percent confidence interval , 0.64 to 1.01 ) . The risk of cardiac arrest or death from arrhythmia among the patients who received treatment with defibrillators was significantly lower than that among the patients discharged without receiving defibrillator treatment ( relative risk , 0.24 ; 95 percent confidence interval , 0.13 to 0.45 ; P<0.001 ) . Neither the rate of cardiac arrest or death from arrhythmia nor the overall mortality rate was lower among the patients assigned to electrophysiologically guided therapy and treated with antiarrhythmic drugs than among the patients assigned to no antiarrhythmic therapy . CONCLUSIONS Electrophysiologically guided antiarrhythmic therapy with implantable defibrillators , but not with antiarrhythmic drugs , reduces the risk of sudden death in high-risk patients with coronary disease BACKGROUND Cardiac resynchronization therapy ( CRT ) improves quality of life ( QoL ) when measured 3 to 6 months after implantation , but whether these effects are sustained is unknown . The CArdiac Resynchronisation-Heart Failure study is the only long-term r and omized trial of CRT with repeated measures of QoL. METHODS Quality of life was measured at baseline and 3 months using generic European Quality of Life-5 Dimensions and disease-specific ( Minnesota Living with Heart Failure ) question naires and at 18 months and study -end using the latter instrument . Median follow-up was 29.6 ( interquartile range 23.6 - 34.6 ) months . RESULTS At baseline , patients had a substantially impaired QoL ( mean European Quality of Life-5 Dimensions score 0.60 , 95 % confidence interval [ CI ] 0.58 - 0.62 ) compared to an age-matched general population ( 0.78 , 95 % CI 0.76 - 0.80 ) . Quality of life improved to a greater extent in patients assigned to CRT at each time point ( P < .0001 ) . By 18 months , the mean difference in disease-specific QoL score was 10.7 ( 95 % CI 7.6 - 13.8 ) in favor of CRT , mostly due to improved physical functioning . Differences were sustained thereafter . Quality -adjusted life-years at 18 months increased by 0.13 ( 95 % CI 0.07 - 0.182 ) and by 0.23 ( 95 % CI 0.13 - 0.33 ) at study -end ( both P < .0001 ) . Little heterogeneity of effect across subgroups was observed . CONCLUSION Cardiac resynchronization therapy improves long-term QoL and survival in patients with moderate to severe heart failure . The effects appear sustained , and therefore , the gain in quality -adjusted life years with CRT should be even greater during longer term follow-up AIMS In CARE-HF , cardiac resynchronization therapy ( CRT ) lowered morbidity and mortality in patients with moderate to severe heart failure . We examined whether baseline and follow-up electrocardiographic characteristics might predict long-term outcome . METHODS AND RESULTS CARE-HF r and omly assigned 409 patients to medical therapy ( MT ) plus CRT , and 404 patients to MT alone . Electrocardiographic measurements were made at baseline during sinus rhythm , and at 3 months during paced or spontaneous rhythm depending on treatment assignment . Favourable outcome was defined as freedom from death , urgent transplantation , or cardiovascular hospitalization . Among patients assigned to CRT , 39 % had unfavourable outcomes including 55 deaths . By single variable analysis , ( i ) prolonged PR interval , left QRS axis ( but not QRS duration ) , and left bundle branch block ( BBB ) at baseline , and ( ii ) heart rate , PR , and QRS duration at 3 months predicted unfavourable outcome . By multiple variable analysis , treatment assignment ( P = 0.0001 ) , PR ( P = 0.0004 ) , and right BBB ( P < 0.00013 ) at baseline predicted outcome , whereas baseline JTc and QRS duration at 3 months predicted all-cause mortality and heart failure hospitalization ( P = 0.0071 ) . CONCLUSION In CARE-HF , QRS duration at baseline did not predict outcome , but QRS at 3 months was a predictor by single variable analysis . Patients with prolonged PR interval and the 5 % of patients with right BBB had a particularly high event rate BACKGROUND Cardiac resynchronisation is a promising new intervention for patients with heart failure , left ventricular systolic dysfunction and ventricular dyssynchrony . OBJECTIVE The CARE-HF trial is design ed to evaluate the long-term effects of cardiac ( atrio-bi-ventricular ) resynchronisation on the mortality and morbidity of patients with heart failure due to left ventricular systolic dysfunction already receiving diuretics and optimal medical therapy with ACE inhibitors and beta-blockers ( where indicated and tolerated ) . METHODS AND RESULTS Approximately 800 patients will be r and omised to device therapy or control and followed for a minimum of 18 months . A pragmatic study design has been chosen that does not attempt to conceal allocation from investigators or patients because it is impossible to guarantee maintenance of blinding for the duration of the study . The end-points committee will adjudicate events in a blinded fashion . Since cardiac resynchronisation may alter other aspects of the management of the patient , as would occur in clinical practice , the study should be considered a comparison of strategies rather than simply of a device . The primary end-point is all-cause mortality or unplanned cardiovascular hospitalisation . The study should complete recruitment during 2002 and report in 2004 BACKGROUND The primary aim of this study was to compare quality -of-life outcome between patients r and omized to implantable cardioverter defibrillator ( ICD ) therapy and patients r and omized to amiodarone treatment in the Canadian Implantable Defibrillator Study ( CIDS ) . A secondary aim was to evaluate the effects on quality -of-life outcomes of receiving shocks from the device . METHODS Quality of life was assessed in 317 English-speaking participants by use of the R and Corporation 's 38-item Mental Health Inventory ( MHI ) and the Nottingham Health Profile ( NHP ) . Assessment s were done in the hospital at baseline and with mailed question naires after 2 , 6 , and 12 months of follow-up . Sixty-two percent of patients completed the follow-up assessment s at 6 and 12 months . RESULTS Repeated measures analysis of variance revealed significant time by treatment group interaction effect on total MHI and the psychological distress and psychological well-being sub-scales , and on 5 of the 7 NHP scales ( energy , physical mobility , emotional reactions , sleep disturbance , and lifestyle impairment ) ( P < .05 ) . Emotional and physical health scores were shown to improve significantly in the ICD group and were either unchanged ( emotional health ) or deteriorated ( energy and physical mobility ) in the amiodarone-treated group by means of post-hoc comparisons . Quality of life did not improve in the subgroup of patients in the ICD-treated group who received > or = 5 shocks from their device . CONCLUSION Quality of life is better with ICD therapy than with amiodarone therapy . The beneficial quality -of-life effects from an ICD are not evident in patients who receive numerous shocks from their device The aim of this study was to investigate the cost‐effectiveness of cardiac resynchronization therapy ( CRT ) in Denmark , Finl and and Sweden . The analysis was based on the CARE‐HF trial , a r and omised clinical trial investigating the efficacy of adding CRT ( n=409 ) to optimal pharmacological treatment ( n=404 ) in patients with moderate to severe heart failure with markers of cardiac dyssynchrony . The average follow‐up time was 29.4 months OBJECTIVES We sought to evaluate the cost implication s of the implantable cardioverter-defibrillator ( ICD ) , using utilization , cost , and survival data from the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II . BACKGROUND This trial showed that prophylactic implantation of a defibrillator reduces the rate of mortality in patients who experienced a previous myocardial infa rct ion and low left ventricular ejection fraction . Given the size of the eligible population , the cost effectiveness of the ICD has substantial implication s. METHODS Our research comprises the cost-effectiveness component of the r and omized controlled trial , MADIT-II , based on utilization , cost , and survival information from 1,095 U.S. patients who were assigned r and omly to receive an ICD or conventional medical care . Utilization data were converted to costs using a variety of national and hospital-specific data . The incremental cost-effectiveness ratio ( iCER ) was calculated as the difference in discounted costs divided by the difference in discounted life expectancy within 3.5 years . Secondary analyses included projections of survival ( using three alternative assumptions ) , corresponding cost assumptions , and the result ing cost-effectiveness ratios until 12 years after r and omization . RESULTS During the 3.5-year period of the study , the average survival gain for the defibrillator arm was 0.167 years ( 2 months ) , the additional costs were 39,200 dollars , and the iCER was 235,000 dollars per year-of-life saved . In three alternative projections to 12 years , this ratio ranged from 78,600 dollars to 114,000 dollars . CONCLUSIONS The estimated cost per life-year saved by the ICD in the MADIT-II study is relatively high at 3.5 years but is projected to be substantially lower over the course of longer time horizons BACKGROUND Indications for cardiac-resynchronization therapy ( CRT ) in patients with heart failure include a prolonged QRS interval ( > or = 120 msec ) , in addition to other functional criteria . Some patients with narrow QRS complexes have echocardiographic evidence of left ventricular mechanical dyssynchrony and may also benefit from CRT . METHODS We enrolled 172 patients who had a st and ard indication for an implantable cardioverter-defibrillator . Patients received the CRT device and were r and omly assigned to the CRT group or to a control group ( no CRT ) for 6 months . The primary end point was the proportion of patients with an increase in peak oxygen consumption of at least 1.0 ml per kilogram of body weight per minute during cardiopulmonary exercise testing at 6 months . RESULTS At 6 months , the CRT group and the control group did not differ significantly in the proportion of patients with the primary end point ( 46 % and 41 % , respectively ) . In a prespecified subgroup with a QRS interval of 120 msec or more , the peak oxygen consumption increased in the CRT group ( P=0.02 ) , but it was unchanged in a subgroup with a QRS interval of less than 120 msec ( P=0.45 ) . There were 24 heart-failure events requiring intravenous therapy in 14 patients in the CRT group ( 16.1 % ) and 41 events in 19 patients in the control group ( 22.3 % ) , but the difference was not significant . CONCLUSIONS CRT did not improve peak oxygen consumption in patients with moderate-to-severe heart failure , providing evidence that patients with heart failure and narrow QRS intervals may not benefit from CRT . ( Clinical Trials.gov number , NCT00132977 [ Clinical Trials.gov ] . ) BACKGROUND As cardiovascular clinical trials improve in sophistication and therapies target specific cardiac mechanisms of death , a more objective and precise system to identify specific cause of death is needed . Ideally , sudden cardiac death would describe patients dying of ventricular tachycardia and ventricular fibrillation . In this context , we explored the precision of current sudden death classification and implication s for clinical trials . METHODS AND RESULTS Deaths were analyzed in 834 patients who received an automatic implantable cardioverter-defibrillator ( ICD ) . Three arrhythmia experts used a st and ard prospect i ve classification system to classify deaths into accepted categories : sudden cardiac , nonsudden cardiac , and noncardiac . New aspects to this study included analysis of autopsy results and ICD interrogation for arrhythmias at the time of death . All of the patients receiving the ICD previously had documented sustained ventricular tachycardia/fibrillation or cardiac arrest . Of the 109 subsequent deaths in the 834-patient data base , 17 ( 16 % ) were classified as sudden cardiac . Compared with the nonsudden cardiac and noncardiac categories , sudden cardiac death was more often identified in out patients ( 59 % versus 10 % ) and witnessed less often ( 41 % versus 86 % ; both P < .001 ) . The autopsy information contradicted and changed the clinical perception of a " sudden cardiac death " in 7 cases ( myocardial infa rct ion [ n = 1 ] , pulmonary embolism [ n = 2 ] , cerebral infa rct ion [ n = 1 ] , ruptured thoracic [ n = 1 ] , and abdominal aortic aneurysms [ n = 2 ] ) . Interpretable ICD interrogation was available in 53 % of the deaths ( 47 % unavailable : buried , programmed off , or other technical reasons ) . When evaluated , only 7 of 17 " sudden deaths " were associated with ICD discharges near the time of death . CONCLUSIONS Even in a group of patients with an ICD , deaths classified as sudden cardiac frequently were not associated with ventricular tachycardia or ventricular fibrillation and were often noncardiac . It is possible to create a wide range of sudden cardiac death rates ( more than fourfold ) using the identical clinical data base despite objective , prespecified criteria . Autopsy results frequently reveal noncardiac causes of clinical events simulating sudden cardiac death . ICD interrogation revealed that ICD discharges were often related to terminal arrhythmias incidental to the primary pathophysiological process leading to death BACKGROUND The Coronary Artery Bypass Graft ( CABG ) Patch Trial tested the hypothesis that prophylactic insertion of an implantable cardioverter-defibrillator ( ICD ) improves survival rates after high-risk CABG . We compared group-specific perioperative morbidity and mortality rates . METHODS AND RESULTS Patients were r and omized intraoperatively to undergo CABG ( control subjects , n = 454 ) or CABG plus ICD implantation ( n = 446 ) . There were no significant differences between groups in the incidence of diabetes , ejection fraction < 0.25 , end-diastolic pressure , prior myocardial infa rct ion , or congestive heart failure . Cardiopulmonary bypass time averaged 106 minutes in control subjects and 127 minutes in the ICD group . At the inception of the trial , investigators were concerned that ICD therapy could increase surgical mortality rates or the incidence of shock , bleeding , congestive heart failure , arrhythmias , or deep sternal wound infection . Of these , only sternal wound infection was significantly more frequent in the ICD group ( 2.2 % versus 0.4 % , P < 0.05 ) . Also more common in the ICD group were infection at a wound or catheter site ( 12 % versus 6 % ) , urinary tract infection ( 4 % versus 1 % ) , pneumonitis ( 8 % versus 4 % ) , respiratory insufficiency ( 13 % versus 8 % ) , transient central nervous system deficit ( 6 % versus 2 % ) , and psychotic reaction ( 4 % versus 1 % ) . The all-cause death rate was 6.7 % in the ICD group and 4.6 % for control patients ( P = NS ) at the time of the last surgical death , postoperative day 48 . CONCLUSIONS Epicardial ICD insertion during CABG is associated with an increase in perioperative infection . Although reporting bias may have influenced the data , if ICD insertion is indicated in CABG patients , metachronous endocardial implantation should be considered UNLABELLED ICDs can affect a patient 's perceived quality -of-life ( QOL ) . This article describes the QOL in patients who participated in The CABG Patch Trial . This trial evaluated the potential benefit of empiric ICD implantation in patients with an increased risk of arrhythmic cardiac death as determined by reduced ejection fraction ( < 0.36 ) and an abnormal signal-averaged ECG . Patients were r and omized to control ( no ICD ) or treatment ( ICD ) limbs . QOL was measured using the SF-36 and other measures among 490 ( 68 % ) of 719 patients available at 6-month follow-up . Analysis was performed on 228 control patients ( those without ICDs ) and 262 patients with ICDs . RESULTS Six months after having CABG surgery , patients in the ICD group had lower levels of psychological well-being than those in the control group . In addition , compared to controls , patients whose ICDs had delivered therapy reported feeling less healthy , had reduced physical and emotional role functioning , and had lower levels of psychological well-being . CONCLUSION Strategies aim ed at easing patients ' adjustment to ICDs should be developed and tested for efficacy in the setting of ICD prophylaxis BACKGROUND The effect of cardiac resynchronization therapy ( CRT ) on physical function and Quality of Life ( QoL ) in patients who require an implantable defibrillator but do not meet guideline criteria for CRT has not been studied in detail . METHODS AND RESULTS This was a r and omized study of 72 patients with high risk of sudden cardiac death , ejection fraction ( EF ) < or = 35 % , mild-to-moderate heart failure symptoms , and QRS > 120 ms . Patients received a CRT defibrillator and were r and omized to CRT turned ON or OFF . Objective and subjective measures were performed at baseline and after 6 months . There was no difference in change in left ventricular end-systolic volume ( ESV ) by radionuclid angiogram scan , the primary endpoint , between the CRT ON group ( DeltaESV = -7 + /- 52 mL ) , and CRT OFF group ( DeltaESV = -30 + /- 47 mL ) . Similarly , echocardiogram measures of ESV and EF showed no difference between the two groups . In the CRT ON group , selected measures of QoL and subjective exercise tolerance but not heart failure symptoms improved significantly . Six-minute walk distance prolonged in the CRT ON group ( baseline 313.6 + /- 114.4 m , 6-month 365.0 + /- 122.5 m , P = 0.01 ) , but the difference in change in walk distance between the two groups was not significant . CONCLUSION Further studies with larger sample size and longer follow-up will be required to allow definite conclusions regarding the potential benefit of CRT in this patient population Background Clinician-assigned New York Heart Association ( NYHA ) class is an established predictor of outcomes in heart failure . This study aims to test whether patients ' self- assessment of functional status by NYHA class predicts hospital admissions , quality of life , and mortality . Methods and Results This was an observational study within a r and omized controlled trial . A total of 293 adult patients diagnosed with heart failure were recruited after an emergency admission at 3 acute hospitals in Norfolk , UK . Outcome measures included number of emergency admissions over 6 months , self-assessed quality of life measured with the Minnesota Living with Heart Failure question naire ( MLHFQ ) and EQ-5D at 6 months , and deaths up to 20 months ' follow-up . Patients were grouped into 3 NYHA groups ( I/II , III , and IV ) based on patients ' self-assigned NYHA class ( SA-NYHA ) . A Poisson model indicated an increased readmission rate associated with higher SA-NYHA class ( adjusted rate ratio 1.21 ; 95 % CI 1.04–1.41 ; P = .02 ) . Higher SA-NYHA class at baseline predicted worse quality of life at 6 months ' follow-up ( P = .002 for MLHFQ ; P = .047 for EQ-5D ) , and was associated with higher mortality rate ( adjusted hazard ratio 1.84 ; 95 % CI 1.10–3.06 ; P = .02 ) . Conclusions SA-NYHA class is predictive of hospitalization , quality of life , and mortality among patients with heart failure BACKGROUND The implantable cardioverter/defibrillator ( ICD ) has been shown to be superior to antiarrhythmic drug therapy for the secondary prevention of sudden cardiac death . Its role in the primary prevention of sudden death after myocardial infa rct ion is unknown . Methods and Results The Defibrillator in Acute Myocardial Infa rct ion Trial ( DINAMIT ) is a r and omized , open-label , parallel-group comparison of ICD therapy versus no ICD therapy in selected survivors of acute myocardial infa rct ion . It will test the hypothesis that reduction of sudden arrhythmogenic death by means of the ICD will result in reduction of overall mortality rates in patients at high risk after acute myocardial infa rct ion . Accordingly , this international multicenter study aims to enroll patients shortly after their infa rct ion ( day 6 to day 40 ) who have reduced left ventricular function ( left ventricular ejection fraction < /=0 . 35 ) and impairment of cardiac autonomic function shown by depressed heart rate variability ( st and ard deviation of normal-to-normal R-R intervals < /=70 ms ) or elevated average 24-hour heart rate ( mean 24-hour R-R interval < /=750 ms , assessed by Holter monitoring ) . Patients will be followed for approximately 3 years on average with subsequent data analysis based on the intent-to-treat principle . Primary outcome is all-cause death . The trial is expected to be completed in 2003 . CONCLUSIONS DINAMIT is the first prospect i ve study to evaluate the benefit of ICD therapy for the primary prevention of sudden cardiac death in patients at high risk after acute myocardial infa rct ion Objectives To evaluate the clinical response to cardiac resynchronisation therapy ( CRT ) in patients with heart failure and a normal QRS duration ( < 120 ms ) . Setting Single centre . Patients 60 patients with heart failure and a normal QRS duration receiving optimal pharmacological treatment ( OPT ) . Interventions Patients were r and omly assigned to CRT ( n=29 ) or to a control group ( OPT , n=31 ) . Cardiovascular magnetic resonance was used in order to avoid scar at the site of left ventricular ( LV ) lead deployment . Main outcome measures The primary end point was a change in 6 min walking distance ( 6-MWD ) . Other measures included a change in quality of life scores ( Minnesota Living with Heart Failure question naire ) and New York Heart Association class . Results In 93 % of implantations , the LV lead was deployed over non-scarred myocardium . At 6 months , the 6-MWD increased with CRT compared with OPT ( p<0.0001 ) , with more patients reaching a ≥25 % increase ( 51.7 % vs 12.9 % , p=0.0019 ) . Compared with OPT , CRT led to an improvement in quality -of-life scores ( p=0.0265 ) and a reduction in NYHA class ( p<0.0001 ) . The composite clinical score ( survival for 6 months free of heart failure hospitalisations plus improvement by one or more NYHA class or by ≥25 % in 6-MWD ) was better in CRT than in OPT ( 83 % vs 23 % , respectively ; p<0.0001 ) . Although no differences in total or cardiovascular mortality emerged between OPT and CRT , patients receiving OPT had a higher risk of death from pump failure than patients assigned to CRT ( HR=8.41 , p=0.0447 ) after a median follow-up of 677.5 days . Conclusions CRT leads to an improvement in symptoms , exercise capacity and quality of life in patients with heart failure and a normal QRS duration . ( Clinical Trials.gov number , NCT00480051 . AIMS MAVERIC was a r and omised clinical trial design ed to test the possibility of prospect ively identifying patients who would benefit most from the implantable cardioverter-defibrillator ( ICD ) by electrophysiology ( EP ) study in the context of secondary prevention of sudden cardiac death ( SCD ) through comparing EP-guided interventions ( anti-arrhythmic drugs , coronary revascularization , and ICD ) against empirical amiodarone therapy . METHODS Two hundred and fourteen survivors of sustained ventricular tachycardia ( VT ) , ventricular fibrillation ( VF ) or SCD were r and omized to either treatment strategy , pre-stratified for haemodynamic status at index event , and followed up for a median of 5 years . RESULTS Of the 106 amiodarone arm patients , 89 ( 84 % ) received the drug and 5 ( 5 % ) received an ICD after crossing over . Of the 108 EP arm patients , 31 ( 29 % ) received an ICD , 46 ( 43 % ) received anti-arrhythmic drugs only ( mainly amiodarone or sotalol ) and 18 ( 17 % ) received coronary revascularization but no ICD . No significant differences in survival or arrhythmia recurrence existed between the two treatment arms after 6 years . However , ICD recipients had a lower mortality than non-ICD recipients , regardless of allocated treatment ( hazard ratio=0.54 , p=0.0391 ) . CONCLUSIONS Prospect i ve selection of patients to receive the ICD by EP study did not improve survival compared with empirical amiodarone therapy among survivors of VT , VF or SCD , whereas ICD implantation improved survival regardless of allocated treatment . On this basis , routine EP study has no role in the management of such patients , who should be offered empirical ICD therapy according to the results of other secondary prevention ICD trials BACKGROUND Cardiac-resynchronization therapy ( CRT ) benefits patients with left ventricular systolic dysfunction and a wide QRS complex . Most of these patients are c and i date s for an implantable cardioverter-defibrillator ( ICD ) . We evaluated whether adding CRT to an ICD and optimal medical therapy might reduce mortality and morbidity among such patients . METHODS We r and omly assigned patients with New York Heart Association ( NYHA ) class II or III heart failure , a left ventricular ejection fraction of 30 % or less , and an intrinsic QRS duration of 120 msec or more or a paced QRS duration of 200 msec or more to receive either an ICD alone or an ICD plus CRT . The primary outcome was death from any cause or hospitalization for heart failure . RESULTS We followed 1798 patients for a mean of 40 months . The primary outcome occurred in 297 of 894 patients ( 33.2 % ) in the ICD-CRT group and 364 of 904 patients ( 40.3 % ) in the ICD group ( hazard ratio in the ICD-CRT group , 0.75 ; 95 % confidence interval [ CI ] , 0.64 to 0.87 ; P<0.001 ) . In the ICD-CRT group , 186 patients died , as compared with 236 in the ICD group ( hazard ratio , 0.75 ; 95 % CI , 0.62 to 0.91 ; P = 0.003 ) , and 174 patients were hospitalized for heart failure , as compared with 236 in the ICD group ( hazard ratio , 0.68 ; 95 % CI , 0.56 to 0.83 ; P<0.001 ) . However , at 30 days after device implantation , adverse events had occurred in 124 patients in the ICD-CRT group , as compared with 58 in the ICD group ( P<0.001 ) . CONCLUSIONS Among patients with NYHA class II or III heart failure , a wide QRS complex , and left ventricular systolic dysfunction , the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure . This improvement was accompanied by more adverse events . ( Funded by the Canadian Institutes of Health Research and Medtronic of Canada ; Clinical Trials.gov number , NCT00251251 . ) The DEFibrillators In Non-Ischemic Cardiomyopathy Treatment Evaluation ( DEFINITE ) was a multi-center , r and omized , investigator-initiated trial . Patients enrolled in the trial had non-ischemic cardiomyopathy ( LVEF < or=35 % ) , a history of symptomatic heart failure and spontaneous arrhythmia ( > 10 PVCs/hr or non-sustained ventricular tachycardia defined as 3 to 15 beats at a rate of > 120 bpm ) on Holter monitor or telemetry within the past 6 months . All patients received st and ard oral medical therapy for heart failure including angiotensin converting enzyme inhibitors and beta-blockers . Patients were r and omized to implantable cardioverter defibrillator ( ICD ) versus no ICD . Patients were followed for 2 to 3 years . The primary endpoint was total mortality . Quality of life and pharmacoeconomics analysis was also performed . A registry tracked patients who met basic inclusion criteria but were not r and omized . We estimated an annual total mortality of 15 % at 2 years in the treatment arm that did not receive an ICD . The ICD was expected to reduce mortality by 50 % . Approximately 229 patients were required in each treatment group . Forty-five centers were included in this trial that was design ed to last an estimated 4 years . Enrollment was projected to occur over 2 1/2 years with a post enrollment follow-up of 1 1/2 years The Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction ( REVERSE ) study is a r and omized controlled trial currently assessing the safety and efficacy of cardiac resynchronization therapy in patients with asymptomatic left ventricular ( LV ) dysfunction with previous symptoms of mild heart failure . This paper describes the baseline characteristics of r and omized patients ; 610 patients with New York Heart Association ( NYHA ) class II ( 82.3 % ) heart failure or asymptomatic ( NYHA class I ) LV dysfunction with previous symptoms ( 17.7 % ) were r and omized in 73 centers . The mean age was 62.5+/-11.0 years , the mean LV ejection fraction was 26.7%+/-7.0 % , and the mean LV end-diastolic diameter was 66.9+/-8.9 mm . A total of 97 % of patients were taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and 95.1 % were taking beta-blockers , which were at the target dose in 35.1 % of patients . Compared with previous r and omized cardiac resynchronization therapy trials , REVERSE patients are on better pharmacologic treatment , are younger , and have a narrower QRS width despite similar LV dysfunction Up to 50 % of patients with chronic systolic heart failure have interventricular conduction delays , such as left bundle branch block , that result in abnormal electrical depolarization of the heart . Prolonged QRS duration results in abnormal interventricular septal wall motion , decreased contractility , reduced diastolic filling time , and prolonged duration of mitral regurgitation , which places the failing heart at a significant mechanical disadvantage . Prolonged QRS duration has been associated with poor outcome in heart failure patients . Atrial-synchronized , biventricular pacing or cardiac resynchronization therapy optimizes atrial-ventricular delay , narrows QRS duration , and seems promising in the management of advanced heart failure patients . Initial studies show improved quality of life and functional capacity compared with baseline or with no pacing . These studies , however , were either uncontrolled or poorly controlled , unblinded or only single-blinded , and enrolled small numbers of patients . The Multicenter InSync R and omized Clinical Evaluation ( MIRACLE ) is a large , prospect i ve , r and omized , double-blind , controlled trial design ed to more definitively evaluate the clinical efficacy and safety of cardiac resynchronization for heart failure . The study is being completed in 3 phases ( an initial pilot phase , a pivotal phase , and an expansion phase ) , enrolling 500 patients with New York Heart Association ( NYHA ) class III and IV systolic heart failure and QRS duration s of 130 ms or more . Prospect ively defined primary end points for the pivotal phase include evaluation of safety ( implant success rate , freedom from stimulator- and ventricular-lead-related complications ) and effects on functional status ( quality of life , NYHA class , 6-minute hall walk distance ) at 6 months . A variety of secondary end points will further define the efficacy and mechanism(s ) of action of cardiac resynchronization in heart failure . The pivotal phase of MIRACLE will conclude in January 2001 Objective : To develop a comprehensive and easily applicable prognostic model predicting mortality risk in patients with moderate to severe heart failure . Design : Prospect i ve follow up study . Setting : Seven general hospitals in the Netherl and s. Patients : 152 out patients with heart failure or patients admitted to hospital because of heart failure , who were included in a r and omised trial to assess the impact of a pharmacist led intervention to improve drug compliance . Duration of follow up was at least 18 months . Main outcome measures : Multivariable logistic regression modelling was used to evaluate information from history , physical examination ( for example , blood pressure ) , drug use , and quality of life question naires that independently contributed to the prediction of death . The area under receiver operating characteristic curves ( AUC ) was used to estimate the predictive ability of the prognostic models . Results : During the 18 months of follow up , 51 patients ( 34 % ) died . Independent predictors of mortality were diabetes mellitus , a history of renal dysfunction ( or higher creatinine ) , New York Heart Association ( NYHA ) functional class III or IV , lower weight or body mass index , lower blood pressure , ankle oedema , and higher scores on a disease specific quality of life question naire . The use of β blockers was predictive of a better prognosis . These factors were used to derive various prediction formulas . A model based on medical history , weight , presence of oedema , and lower blood pressure had an AUC of 0.77 . Addition of use of β blockers to this model improved the AUC to 0.80 . Addition of NYHA class increased the AUC to 0.84 . Data on quality of life did not improve the AUC further ( AUC 0.85 ) . Conclusions : A prognostic model produced on the basis of easily obtainable information from medical history and physical examination can adequately stratify heart failure patients according to their short term risk of death BACKGROUND Implantable cardioverter-defibrillators ( ICDs ) are widely used to prevent fatal outcomes associated with life-threatening arrhythmic episodes in a variety of cardiac diseases . These ICDs rely on transvenous leads for cardiac sensing and defibrillation . A new entirely subcutaneous ICD overcomes problems associated with transvenous leads . However , the role of the subcutaneous ICD as an adjunctive or primary therapy in patients at risk for sudden cardiac death is unclear . STUDY DESIGN The PRAETORIAN trial is an investigator-initiated , r and omized , controlled , multicenter , prospect i ve 2-arm trial that outlines the advantages and disadvantages of the subcutaneous ICD . Patients with a class I or IIa indication for ICD therapy without an indication for bradypacing or tachypacing are included . A total of 700 patients are r and omized to either the subcutaneous or transvenous ICD ( 1:1 ) . The study is powered to cl aim noninferiority of the subcutaneous ICD with respect to the composite primary endpoint of inappropriate shocks and ICD-related complications . After noninferiority is established , statistical analysis is done for potential superiority . Secondary endpoint comparisons of shock efficacy and patient mortality are also made . CONCLUSION The PRAETORIAN trial is a r and omized trial that aims to gain scientific evidence for the use of the subcutaneous ICD compared with the transvenous ICD in a population of patients with conventional ICD with respect to major ICD-related adverse events . This trial is registered at Clinical Trials.gov with trial ID NCT01296022 BACKGROUND Implantable cardioverter defibrillators ( ICDs ) effectively prevent sudden cardiac death , but selection of appropriate patients for implantation is complex . We evaluated whether risk stratification based on risk of sudden cardiac death alone was sufficient to predict the effectiveness and cost-effectiveness of the ICD . METHODS We developed a Markov model to evaluate the cost-effectiveness of ICD implantation compared with empiric amiodarone treatment . The model incorporated mortality rates from sudden and nonsudden cardiac death , noncardiac death and costs for each treatment strategy . We based our model inputs on data from r and omized clinical trials , registries , and meta-analyses . We assumed that the ICD reduced total mortality rates by 25 % , relative to use of amiodarone . RESULTS The relationship between cost-effectiveness of the ICD and the total annual cardiac mortality rate is U-shaped ; cost-effectiveness becomes unfavorable at both low and high total cardiac mortality rates . If the annual total cardiac mortality rate is 12 % , the cost-effectiveness of the ICD varies from $ 36,000 per quality -adjusted life-year ( QALY ) gained when the ratio of sudden cardiac death to nonsudden cardiac death is 4 to $ 116,000 per QALY gained when the ratio is 0.25 . CONCLUSIONS The cost-effectiveness of ICD use relative to amiodarone depends on total cardiac mortality rates as well as the ratio of sudden to nonsudden cardiac death . Studies of c and i date diagnostic tests for risk stratification should distinguish patients who die suddenly from those who die nonsuddenly , not just patients who die suddenly from those who live INTRODUCTION Implantable cardioverter-defibrillator ( ICD ) longevity is crucial for both patients and public health systems because it determines the number of surgical ICD replacements , which can generally be considered an additional risk factor for complications , and the cost-effectiveness of ICD therapy . Our objective was to obtain insight into the " real-world " longevities of implantable cardioverter-defibrillators , which quite often differ from those stated in the manufacturers ' declarations . METHODS AND RESULTS On the basis of a prospect i ve data base , we analyzed all ICD implantations performed in our hospital from June 1988 to June 2009 . We studied 980 patients ( follow-up 58 ± 51 months ) with 1,502 ICDs and all respective data until August 2010 . We compared the percentage of still operating ICDs at different points in time in relation to manufacturers , types of device ( single chamber 623 , dual chamber 588 , cardiac resynchronization therapy ICDs [ CRT-D ] 291 ) , and amount of right ventricular pacing ( VP ) . We found distinct differences between the mean lifespans of ICDs of different manufacturers ( Biotronik 4.3 years , Sorin 4.5 years , Guidant/Boston Scientific 4.7 years , St. Jude Medical 5 years , Medtronic 5.8 years ) . CRT-D devices ( hazard ratio [ HR ] 1.778 , P = 0.0005 ) were associated with an elevated annual relative risk for device replacement while a decrease in the proportion of VP ( HR 0.934 for each 10 % decrease in VP , P < 0.0001 ) and Medtronic ICDs were associated with a reduced risk of device replacement ( HR 0.544 , P < 0.0001 ) . CONCLUSION CRT-Ds and an elevated percentage of VP are associated with a significantly elevated risk for device replacement , while Medtronic ICDs showed the longest lifespans BACKGROUND Previous studies have suggested that cardiac resynchronization achieved through atrial-synchronized biventricular pacing produces clinical benefits in patients with heart failure who have an intraventricular conduction delay . We conducted a double-blind trial to evaluate this therapeutic approach . METHODS Four hundred fifty-three patients with moderate-to-severe symptoms of heart failure associated with an ejection fraction of 35 percent or less and a QRS interval of 130 msec or more were r and omly assigned to a cardiac-resynchronization group ( 228 patients ) or to a control group ( 225 patients ) for six months , while conventional therapy for heart failure was maintained . The primary end points were the New York Heart Association functional class , quality of life , and the distance walked in six minutes . RESULTS As compared with the control group , patients assigned to cardiac resynchronization experienced an improvement in the distance walked in six minutes ( + 39 vs. + 10 m , P=0.005 ) , functional class ( P<0.001 ) , quality of life ( -18.0 vs. -9.0 points , P= 0.001 ) , time on the treadmill during exercise testing ( + 81 vs. + 19 sec , P=0.001 ) , and ejection fraction ( + 4.6 percent vs. -0.2 percent , P<0.001 ) . In addition , fewer patients in the group assigned to cardiac resynchronization than control patients required hospitalization ( 8 percent vs. 15 percent ) or intravenous medications ( 7 percent vs. 15 percent ) for the treatment of heart failure ( P<0.05 for both comparisons ) . Implantation of the device was unsuccessful in 8 percent of patients and was complicated by refractory hypotension , bradycardia , or asystole in four patients ( two of whom died ) and by perforation of the coronary sinus requiring pericardiocentesis in two others . CONCLUSIONS Cardiac resynchronization results in significant clinical improvement in patients who have moderate-to-severe heart failure and an intraventricular conduction delay Non ischemic dilated cardiomyopathy ( NIDCM ) is a substrate for sudden cardiac death . Treatment with amiodarone may have a positive or neutral survival benefit . The role of ICD therapy in the primary prevention of sudden cardiac death in asymptomatic NIDCM patients is not clear . The purpose of the Amiodarone versus Implantable Defibrillator ( AMIOVIRT ) study was to compare total mortality , arrhythmia-free survival , quality of life and costs of therapy in patients with NIDCM , asymptomatic non-sustained ventricular tachycardia ( NSVT ) and left ventricular ejection fraction < or=0.35 who were r and omized to therapy with amiodarone ( 52 patients ) or an ICD ( 51 patients ) . At the first scheduled interim analysis , the previously determined stopping rule for futility was reached and the study was stopped . There was no statistically significant difference in the 1- and 3-year survival rates in the patients who received amiodarone compared with those who received an ICD ( 90 % and 87 % for amiodarone group versus 96 % and 88 % for ICD group ; p = 0.8 ) . There was a trend towards improved arrhythmia-free survival rates ( p = 0.1 ) , and cost of medical care ( 8,879 dollars vs. 22,039 dollars , p = 0.1 ) in the patients who were treated with amiodarone as compared to the patients who were treated with an ICD . At one year , the quality of life measures were not significantly different ( p = 0.1 ) BACKGROUND Unsustained ventricular tachycardia in patients with previous myocardial infa rct ion and left ventricular dysfunction is associated with a two-year mortality rate of about 30 percent . We studied whether prophylactic therapy with an implanted cardioverter-defibrillator , as compared with conventional medical therapy , would improve survival in this high-risk group of patients . METHODS Over the course of five years , 196 patients in New York Heart Association functional class I , II , or III with prior myocardial infa rct ion ; a left ventricular ejection fraction < or = 0.35 ; a documented episode of asymptomatic unsustained ventricular tachycardia ; and inducible , nonsuppressible ventricular tachyarrhythmia on electrophysiologic study were r and omly assigned to receive an implanted defibrillator ( n = 95 ) or conventional medical therapy ( n=101 ) . We used a two-sided sequential design with death from any cause as the end point . RESULTS The base-line characteristics of the two treatment groups were similar . During an average follow-up of 27 months , there were 15 deaths in the defibrillator group ( 11 from cardiac causes ) and 39 deaths in the conventional-therapy group ( 27 from cardiac causes ) ( hazard ratio for overall mortality , 0.46 ; 95 percent confidence interval , 0.26 to 0.82 ; P=0.009 ) . There was no evidence that amiodarone , beta-blockers , or any other antiarrhythmic therapy had a significant influence on the observed hazard ratio . CONCLUSIONS In patients with a prior myocardial infa rct ion who are at high risk for ventricular tachyarrhythmia , prophylactic therapy with an implanted defibrillator leads to improved survival as compared with conventional medical therapy The CABG Patch Trial is testing the hypothesis that prophylactic use of implantable cardiac defibrillators ( ICDs ) will improve survival in high-risk coronary heart disease patients undergoing CABG surgery . The original design called for 800 patients to be r and omized to ICD prophylaxis or to no therapy and followed for 2 to 6.5 years ( average , 40 months ) to a common termination date . Since the ICD pulse generators used in this trial lasted about 42 months , the original design required ICD replacement in many patients . At its first two meetings in 1993 , the Data and Safety Monitoring Board ( DSMB ) formalized a plan to adjust sample size in October 1994 if the control group mortality rate was lower than expected . In June 1994 , an unanticipated and unique event -- a subpoena from the Office of the Inspector General (OIG)--made it impossible to replace about half of the ICD generators and threatened to shorten follow-up substantially . If follow-up had been stopped on the date originally planned , but without replacing ICDs , the average follow-up would have fallen from 40 months to about 33 months . Also , in October 1994 , the control group mortality rate was found to be somewhat lower than expected . Together , the abbreviated follow-up and lower control group mortality threatened to reduce power substantially . The DSMB review ed several options for restoring power . Because mortality rates in the first month after CABG surgery were about seven times as high as thereafter and because ICD therapy did not reduce surgical mortality ( death during the first 30 days ) , extending the follow-up benefits power more than does increasing the sample size . However , the limit on extending follow-up was 42 months ( the expected battery life of the ICD ) . Data from the ICD-treated group was not review ed or considered in making the decision . After review ing many options for restoring power , the DSMB recommended that the sample size be increased from 800 to 900 patients and that almost all patients be followed for 42 months . This recommendation extended follow-up for 2 years beyond the original termination date planned for the trial and dictated that patients close out after 42 months rather than on a common termination date BACKGROUND Implantable cardioverter-defibrillator ( ICD ) therapy significantly prolongs life in patients at increased risk for sudden death from depressed left ventricular function . However , whether this increased longevity is accompanied by deterioration in the quality of life is unclear . METHODS In a r and omized trial , we compared ICD therapy or amiodarone with state-of-the-art medical therapy alone in 2521 patients who had stable heart failure with depressed left ventricular function . We prospect ively measured quality of life at baseline and at months 3 , 12 , and 30 ; data collection was 93 to 98 % complete . The Duke Activity Status Index ( which measures cardiac physical functioning ) and the Medical Outcomes Study 36-Item Short-Form Mental Health Inventory 5 ( which measures psychological well-being ) were prespecified primary outcomes . Multiple additional quality -of-life outcomes were also examined . RESULTS Psychological well-being in the ICD group , as compared with medical therapy alone , was significantly improved at 3 months ( P=0.01 ) and at 12 months ( P=0.003 ) but not at 30 months . No clinical ly or statistically significant differences in physical functioning among the study groups were observed . Additional quality -of-life measures were improved in the ICD group at 3 months , 12 months , or both , but there was no significant difference at 30 months . ICD shocks in the month preceding a scheduled assessment were associated with a decreased quality of life in multiple domains . The use of amiodarone had no significant effects on the primary quality -of-life outcomes . CONCLUSIONS In a large primary -prevention population with moderately symptomatic heart failure , single-lead ICD therapy was not associated with any detectable adverse quality -of-life effects during 30 months of follow-up The Antiarrhythmics Versus Implantable Defibrillators ( AVID ) study compares a strategy of initial treatment with an implantable cardioverter-defibrillator ( ICD ) to a strategy of initial treatment with an antiarrhythmic drug to prevent death in patients with a history of ventricular fibrillation or hemodynamically compromising ventricular tachycardia , or both . Neither arrhythmia can have been due to a transient or correctable cause . The principle exclusions are a contraindication to amiodarone therapy and inability to undergo ICD implantation . Antiarrhythmic drug therapy includes empiric amiodarone and guided sotalol . The ICDs allowed are advanced generation devices , and most are implanted transvenously . The primary end point of the study is total mortality . Secondary end points are cost and quality of life . The study was design ed in 2 phases . The pilot phase enrolled 200 patients between June 1993 and June 1994 . Data collected during the pilot phase confirmed that the trial is feasible . An additional 1,000 patients will be enrolled between June 1994 and March 1997 . It is anticipated that all 1,200 patients will be followed until September 1998 , and will be included in the intention-to-treat analysis The Cardiac Resynchronization‐Heart Failure ( CARE‐HF ) study helped establish an important role for cardiac resynchronization therapy ( CRT ) in the management of selected patients with heart failure . We now report the long‐term outcome during and subsequent to the r and omized trial OBJECTIVES The purpose of this study was to investigate the factors related to sex-specific outcomes for death and heart failure events in the MADIT-CRT ( Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy ) trial . BACKGROUND In the MADIT-CRT trial , women seemed to achieve a better result from resynchronization therapy than men . METHODS All 1,820 patients ( 453 female and 1,367 male ) enrolled in the MADIT-CRT trial were included in this sex-specific outcome analysis that compared the effect of cardiac resynchronization therapy with defibrillator ( CRT-D ) relative to implanted cardioverter-defibrillator ( ICD ) on death or heart failure ( whichever came first ) , heart failure only , and death at any time . RESULTS Female patients were more likely to have nonischemic cardiomyopathy and left bundle branch block and less likely to have renal dysfunction than male patients . Overall , female patients had a better result from CRT-D therapy than male patients , with a significant 69 % reduction in death or heart failure ( hazard ratio : 0.31 , p < 0.001 ) and 70 % reduction in heart failure alone ( hazard ratio : 0.30 , p < 0.001 ) . Women had a significant 72 % reduction in all-cause mortality in the total population ( hazard ratio : 0.28 , p = 0.02 ) and significant 82 % and 78 % reductions in mortality in those with QRS ≥ 150 ms and with left bundle branch block conduction disturbance , respectively , with sex-by-treatment interactions for mortality reduction significant at p < 0.05 in each of these 3 patient groups . These beneficial CRT-D effects among women were associated with consistently greater echocardiographic evidence of reverse cardiac remodeling in women than in men . CONCLUSIONS Women in the MADIT-CRT trial obtained significantly greater reductions in death or heart failure ( whichever came first ) , heart failure alone , and all-cause mortality with CRT-D therapy than men , with consistently greater echocardiographic evidence of reverse cardiac remodeling in women than in men . ( Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy [ MADIT-CRT ] ; NCT00180271 ) |
13,530 | 24,931,518 | In summary , the currently available evidence ( one RCT ) is not sufficient to conclude that WBR plus chemotherapy and chemotherapy alone have similar effects on overall survival in people with PCNSL .
The findings suggest that the addition of radiotherapy ( WBR ) to chemotherapy may increase progression-free survival , but may also increase the incidence of neurotoxicity compared to chemotherapy only ( methotrexate monotherapy ) . | BACKGROUND Prior to the introduction of the chemotherapeutic agent methotrexate , radiotherapy was the sole , first-line option for the treatment of individuals with primary central nervous system lymphoma ( PCNSL ) , Now that methotrexate is available , the role of radiotherapy in the treatment of PCNSL has been called into question .
Although various studies suggest promising results with regard to overall and progression-free survival with the use of chemotherapeutic regimens alone as well as in combination with radiotherapy , no evidence -based st and ard regimen has yet been defined .
OBJECTIVES The objective of this review was to assess and summarise the evidence available regarding the efficacy and tolerability of radiotherapy in addition to chemotherapy in the treatment of immunocompetent individuals with PCNSL . | PURPOSE A multicenter , phase II study of single-agent , intravenous methotrexate in newly diagnosed non-AIDS-related primary CNS lymphoma was conducted in the New Approaches to Brain Tumor Therapy ( NABTT ) CNS Consortium . METHODS Methotrexate ( 8 g/m(2 ) ) was initially administered every 2 weeks . The primary end point was radiographic CR or PR , as defined by st and ard radiographic criteria , and secondary end points were survival and drug-related toxicity . RESULTS Twenty-five patients were enrolled with a mean age of 60 years and median Karnofsky Performance Score of 80 . Three of 14 patients who underwent lumbar puncture had malignant cells on CSF cytopathology , and five of 25 patients had ocular involvement . Two patients could not be evaluated for the primary end point because of the absence of measurable disease in one and death before radiologic imaging in another . All patients have completed the treatment program or progressed . Among 23 patients , there were 12 CR ( 52 % ) , five PR ( 22 % ) , one ( 4 % ) with stable disease , and five progressions ( 22 % ) while on therapy . Seven patients died of tumor progression , and two died of other causes . Median progression-free survival was 12.8 months . Median overall survival for the entire group had not been reached at 22.8 + months . The toxicity of this regimen was modest , with no grade 3 or 4 toxicity in 13 of 25 patients , grade 3 toxicity in eight of 25 patients , and grade 4 toxicity in four of 25 patients after 287 cycles of chemotherapy . CONCLUSION These results indicate that high-dose methotrexate is associated with modest toxicity and a radiographic response proportion ( 74 % ) comparable to more toxic regimens PURPOSE Primary CNS lymphoma ( PCNSL ) is an aggressive primary brain tumor . Cranial irradiation alone rarely results in long-term disease control or prolonged survival . We prospect ively studied the use of combination chemotherapy plus cranial irradiation in newly diagnosed patients with PCNSL . PATIENTS AND METHODS We enrolled 102 newly diagnosed , immunocompetent patients with PCNSL ; 98 were assessable . Patients first received five cycles of methotrexate 2.5 g/m(2 ) , vincristine , procarbazine , and intraventricular methotrexate ( 12 mg ) . Whole-brain radiotherapy ( RT ) was administered to a total dose of 45 Gy and all patients received high-dose cytarabine after RT . RESULTS Fifty-eight percent of patients with measurable disease had a complete response to preirradiation chemotherapy and 36 % had a partial ( > 50 % ) response , for a 94 % response rate . Median progression-free survival was 24.0 months and overall survival was 36.9 months . Age was an important prognostic factor ; median survival was 50.4 months in patients younger than 60 and only 21.8 months in those aged 60 or older ( P < .001 ) . Fifty-three percent of patients had grade 3 or 4 toxicity during induction chemotherapy , half of which was hematologic . However , 12 patients ( 15 % ) experienced severe delayed neurologic toxicity , eight of whom died . CONCLUSION This is the first multicenter trial demonstrating improved survival with the combination of chemotherapy plus RT compared with previous reports of RT alone . A high-dose methotrexate-based regimen produced a high response rate before RT was administered . High-dose methotrexate combined with cranial irradiation is an effective therapeutic approach to PCNSL , but neurotoxicity is a delayed risk of this approach Summary Purpose : To determine whether a lower dose of hyperfractionated whole brain radiation reduces central nervous system morbidity without compromising survival for primary CNS lymphoma ( PCNSL ) patients receiving combined modality treatment . Material s and Methods : One hundred and two patients received a course of pre-radiation chemotherapy , followed by whole brain radiation , followed by cytosine-arabinoside . Initial radiation dose was 45 Gy/25 fractions ( RT ) then the study was amended to reduce this dose for complete responders to induction chemotherapy to 36 Gy/30 fractions/3 weeks ( HFX ) . Eighty-two patients received radiotherapy and were evaluable for toxicity analysis ( 66 RT patients and 16 HFX patients ) . MMSE scores and survival for the 40 patients who received radiotherapy after complete response to chemotherapy ( 27 RT and 13 HFX ) were compared . There were no notable differences in pre-treatment patient characteristics between the RT and HFX groups . Results : Neurotoxicity : By 4 years , there were 8/82 ( 10 % ) grade 5 neurotoxicities which included 2/16 ( 13 % ) grade 5 encephalopathies and 0/27 in the RT group of complete responders to chemotherapy . Survival : There was no statistically significant difference in overall or progression-free survival ( PFS ) between the chemotherapy-complete responders who received RT and HFX . Cognitive function testing : MMSE scores improved at 8 months across both treatment groups . Analysis of the area under the MMSE curve at 8 months showed no statistically significant difference between RT and HFX groups ( P=0.81 ) . Leukoencephalopathy occurred later in the HFX group than in the RT patients . Conclusion : Although the HFX schedule represented a 25 % reduction in biologically effective tumor dose in comparison , PFS and overall survival were not significantly affected . The HFX regimen delayed but did not eliminate severe neurotoxicity from chemoradiation in PCNSL patients BACKGROUND High-dose methotrexate is the st and ard of care for patients with newly diagnosed primary CNS lymphoma . The role of whole brain radiotherapy is controversial because delayed neurotoxicity limits its acceptance as a st and ard of care . We aim ed to investigate whether first-line chemotherapy based on high-dose methotrexate was non-inferior to the same chemotherapy regimen followed by whole brain radiotherapy for overall survival . METHODS Immunocompetent patients with newly diagnosed primary CNS lymphoma were enrolled from 75 centres and treated between May , 2000 , and May , 2009 . Patients were allocated by computer-generated block r and omisation to receive first-line chemotherapy based on high-dose methotrexate with or without subsequent whole brain radiotherapy , with stratification by age ( < 60 vs ≥60 years ) and institution ( Berlin vs Tübingen vs all other sites ) . The biostatistics centre assigned patients to treatment groups and informed local centres by fax ; physicians and patients were not masked to treatment group after assignment . Patients enrolled between May , 2000 , and August , 2006 , received high-dose methotrexate ( 4 g/m(2 ) ) on day 1 of six 14-day cycles ; thereafter , patients received high-dose methotrexate plus ifosfamide ( 1·5 g/m(2 ) ) on days 3 - 5 of six 14-day cycles . In those assigned to receive first-line chemotherapy followed by radiotherapy , whole brain radiotherapy was given to a total dose of 45 Gy , in 30 fractions of 1·5 Gy given daily on weekdays . Patients allocated to first-line chemotherapy without whole brain radiotherapy who had not achieved complete response were given high-dose cytarabine . The primary endpoint was overall survival , and analysis was per protocol . Our hypothesis was that the omission of whole brain radiotherapy does not compromise overall survival , with a non-inferiority margin of 0·9 . This trial is registered with Clinical Trials.gov , number NCT00153530 . FINDINGS 551 patients ( median age 63 years , IQR 55 - 69 ) were enrolled and r and omised , of whom 318 were treated per protocol . In the per- protocol population , median overall survival was 32·4 months ( 95 % CI 25·8 - 39·0 ) in patients receiving whole brain radiotherapy ( n=154 ) , and 37·1 months ( 27·5 - 46·7 ) in those not receiving whole brain radiotherapy ( n=164 ) , hazard ratio 1·06 ( 95 % CI 0·80 - 1·40 ; p=0·71 ) . Thus our primary hypothesis was not proven . Median progression-free survival was 18·3 months ( 95 % CI 11·6 - 25·0 ) in patients receiving whole brain radiotherapy , and 11·9 months ( 7·3 - 16·5 ; p=0·14 ) in those not receiving whole brain radiotherapy . Treatment-related neurotoxicity in patients with sustained complete response was more common in patients receiving whole brain radiotherapy ( 22/45 , 49 % by clinical assessment ; 35/49 , 71 % by neuroradiology ) than in those who did not ( 9/34 , 26 % ; 16/35 , 46 % ) . INTERPRETATION No significant difference in overall survival was recorded when whole brain radiotherapy was omitted from first-line chemotherapy in patients with newly diagnosed primary CNS lymphoma , but our primary hypothesis was not proven . The progression-free survival benefit afforded by whole brain radiotherapy has to be weighed against the increased risk of neurotoxicity in long-term survivors BACKGROUND We investigated the efficacy and safety of t and em high-dose methotrexate ( HD-MTX ) induction followed by high-dose busulfan/thiotepa ( HD-BuTT ) with autologous peripheral blood stem-cell transplantation ( aPBSCT ) and response-adapted whole-brain radiation therapy ( WBRT ) in patients with newly diagnosed primary central nervous system lymphoma . PATIENTS AND METHODS Twenty-three patients were treated with HD-MTX on days 1 and 10 . In case of at least a partial remission ( PR ) , HD-BuTT followed by aPBSCT was given . Patients without response to induction or without complete remission ( CR ) after HD-BuTT received WBRT . RESULTS Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13 % . CR/PR rates for all patients ( n = 23 ) were 70%/13 % . There were three deaths during therapy . With longer follow-up three neurotoxic deaths occurred in irradiated patients ( n = 9 ) , while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT . At a median follow-up of 15 months ( range 1 - 69 ) median event-free survival ( EFS ) and overall survival ( OS ) for all patients were 17 and 20 months ( Kaplan-Meier ) , after HD-BuTT 27 months and " not reached " , respectively . Estimated 2-year EFS and OS were 45 % and 48 % for all patients versus 56 % and 61 % for the HD-BuTT group , respectively . CONCLUSION MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen . Median survival for patients treated with high-dose chemotherapy is not reached yet . The induction regimen needs optimisation . In this study WBRT was associated with a high incidence of severe neurotoxicity 1522 Background : The role of adjuvant whole-brain irradiation ( WBI ) in PCNSL remains to be defined . Eliminating WBI from the initial treatment could reduce neurotoxicity but also adversly affect disease control and survival . METHODS Fifty-six patients were included in this prospect i ve multicenter trial to evaluate the role of adjuvant WBI in PCNSL : . All received chemotherapy ( CHX ) composed of carmustine , high-dose methotrexate ( HD-MTX ) 1.5 g/m2 , procarbazine , and dexamethasone ( only in course 1 ) . Patients without complete response ( CR ) received salvage chemotherapy with idarubicine and ifosfamide or high-dose cytarabine . Patients with CR after CHX were r and omized to either WBI or one additional CHX course . RESULTS The CR rate after CHX was 61 % ( 34/56 ) , but only 23 patients were r and omized to the two study arms . With a median follow-up of 40 months median overall survival ( OAS ) of all 24 patients without adjuvant WBI was 28.5 months ( 95 % CI 7.7 - 49.2 months ) , that of all 10 responders with adjuvant WBI 12.8 months ( 95 % CI 0 - 40.4 months ; P=0.97 ) . Responders to CHX had significantly longer survival than non-responders ( 18.2 versus 9.9 months , P=0.02 ) . Median OAS was significantly longer at institutions accruing at least 4 patients than at those with fewer patients ( 31.5 versus 9.5 months , P=0.03 ) . Late neurotoxicity developed in 5/24 ( 21 % ) patients younger than 60 years as compared to 6/32 ( 19 % ) older patients ( P=0.84 ) and in 6/28 patients after WBI as compared to 5/22 without WBI treatment ( P=0.91 ) . CONCLUSIONS Response to CHX and treating institution were predictive of survival . The neurotoxicity rate was independent of age and WBI . The high drop-out and low r and omization experience of this study led to a similar ongoing multicenter trial with HD-MTX monotherapy and upfront r and omization . No significant financial relationships to disclose BACKGROUND Chemotherapy with high-dose methotrexate is the conventional approach to treat primary CNS lymphomas , but superiority of polychemotherapy compared with high-dose methotrexate alone is unproven . We assessed the effect of adding high-dose cytarabine to methotrexate in patients with newly diagnosed primary CNS lymphoma . METHODS This open , r and omised , phase 2 trial was undertaken in 24 centres in six countries . 79 patients with non-Hodgkin lymphoma exclusively localised into the CNS , cranial nerves , or eyes , aged 18 - 75 years , and with Eastern Cooperative Oncology Group performance status of 3 or lower and measurable disease were central ly r and omly assigned by computer to receive four courses of either methotrexate 3.5 g/m(2 ) on day 1 ( n=40 ) or methotrexate 3.5 g/m(2 ) on day 1 plus cytarabine 2 g/m(2 ) twice a day on days 2 - 3 ( n=39 ) . Both regimens were administered every 3 weeks and were followed by whole-brain irradiation . The primary endpoint was complete remission rate after chemotherapy . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00210314 . FINDINGS All r and omly assigned participants were analysed . After chemotherapy , seven patients given methotrexate and 18 given methotrexate plus cytarabine achieved a complete remission , with a complete remission rate of 18 % ( 95 % CI 6 - 30 ) and 46 % ( 31 - 61 ) , respectively , ( p=0.006 ) . Nine patients receiving methotrexate and nine receiving methotrexate plus cytarabine achieved a partial response , with an overall response rate of 40 % ( 25 - 55 ) and 69 % ( 55 - 83 ) , respectively , ( p=0.009 ) . Grade 3 - 4 haematological toxicity was more common in the methotrexate plus cytarabine group than in the methotrexate group ( 36 [ 92 % ] vs six [ 15 % ] ) . Four patients died of toxic effects ( three vs one ) . INTERPRETATION In patients aged 75 years and younger with primary CNS lymphoma , the addition of high-dose cytarabine to high-dose methotrexate provides improved outcome with acceptable toxicity compared with high-dose methotrexate alone . FUNDING Swiss Cancer League PURPOSE Our goals were to evaluate the safety of adding rituximab to methotrexate (MTX)-based chemotherapy for primary CNS lymphoma , determine whether additional cycles of induction chemotherapy improve the complete response ( CR ) rate , and examine effectiveness and toxicity of reduced-dose whole-brain radiotherapy ( WBRT ) after CR . PATIENTS AND METHODS Thirty patients ( 17 women ; median age , 57 years ; median Karnofsky performance score , 70 ) were treated with five to seven cycles of induction chemotherapy ( rituximab , MTX , procarbazine , and vincristine [ R-MPV ] ) as follows : day 1 , rituximab 500 mg/m2 ; day 2 , MTX 3.5 gm/m2 and vincristine 1.4 mg/m2 . Procarbazine 100 mg/m2/d was administered for 7 days with odd-numbered cycles . Patients achieving CR received dose-reduced WBRT ( 23.4 Gy ) , and all others received st and ard WBRT ( 45 Gy ) . Two cycles of high-dose cytarabine were administered after WBRT . CSF levels of rituximab were assessed in selected patients , and prospect i ve neurocognitive evaluations were performed . RESULTS With a median follow-up of 37 months , 2-year overall and progression-free survival was 67 % and 57 % , respectively . Forty-four percent of patients achieved a CR after five or fewer cycles , and 78 % after seven cycles . The overall response rate was 93 % . Nineteen of 21 CR patients received the planned 23.4 Gy WBRT . The most commonly observed grade 3 to 4 toxicities included neutropenia ( 43 % ) , thrombocytopenia ( 36 % ) , and leukopenia ( 23 % ) . No treatment-related neurotoxicity has been observed . CONCLUSION The addition of rituximab to MPV increased the risk of significant neutropenia requiring routine growth factor support . Additional cycles of R-MPV nearly doubled the CR rate . Reduced-dose WBRT was not associated with neurocognitive decline , and disease control to date is excellent PURPOSE To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide , doxorubicin ( Adriamycin ) , vincristine , and dexamethasone ( CHOD ) plus bis-chloronitrosourea ( BCNU ) , cytosine arabinoside , and methotrexate ( BVAM ) followed by whole-brain irradiation ( WBRT ) for patients with primary central nervous system lymphoma ( PCNSL ) . METHODS AND MATERIAL S Patients 70 years old and younger with newly diagnosed , biopsy-proven PCNSL received one cycle of CHOD followed by two cycles of BVAM . Patients then received WBRT , 30.6 Gy , if a complete response was evoked , or 50.4 Gy if the response was less than complete ; both doses were given in 1.8-Gy daily fractions . The primary efficacy endpoint was 1-year survival . RESULTS Thirty-six patients ( 19 men , 17 women ) enrolled between 1995 and 2000 . Median age was 60.5 years ( range , 34 to 69 years ) . Thirty ( 83 % ) patients had baseline Eastern Cooperative Oncology Group performance scores of 0 to 1 . All 36 patients were eligible for survival and response evaluations . Median time to progression was 12.3 months , and median survival was 18.5 months . The percentages of patients alive at 1 , 2 , and 3 years were 64 % , 36 % , and 33 % , respectively . The best response was complete response in 10 patients and immediate progression in 7 patients . Ten ( 28 % ) patients had at least one grade 3 or higher neurologic toxicity . CONCLUSIONS This regimen did improve the survival of PCNSL patients but also caused substantial toxicity . The improvement in survival is less than that reported with high-dose methotrexate-based therapies The best therapeutic management in primary CNS lymphomas remains to be defined due to the small size and short follow-up of retrospective series , method ological pitfalls and limited number of prospect i ve studies , and the paucity of r and omized trials . This review focuses on the current therapeutic approaches , most commonly used drugs , role of intrathecal chemotherapy and indications for consolidation radiotherapy , providing recommendations for ordinary clinical practice . Some important therapeutic issues , such as the management of meningeal and intraocular lymphomas , as well as the relevance of salvage therapy as a playground for evaluation of new drugs , are also analyzed . Finally , the main open questions , as well as current and expected investigation trends are discussed PURPOSE To assess the effect of a reduced dose of radiotherapy ( RT ) in patients with primary CNS lymphoma ( PCNSL ) responding to the cyclophosphamide , doxorubicin , vincristine , and dexamethasone (CHOD)/carmustine , vincristine , methotrexate , and cytarabine ( BVAM ) regimen . PATIENTS AND METHODS Patients received one cycle of CHOD and two of BVAM . In the first trial , all 31 patients received 45-Gy whole-brain RT ( CHOD/BVAM I ) . In the second , with 26 patients , RT dose was reduced to 30.6 Gy if there was a complete response ( CR ) after chemotherapy ( CHOD/BVAM II ) . RESULTS Age , performance status , and chemotherapy received were similar in both protocol s. CR rate at the end of all treatment was 68 % for CHOD/BVAM I and 77 % and for CHOD/BVAM II . Treatment modality was the only predictor of relapse , with 3-year relapse risks of 29 % and 70 % for CHOD/BVAM I and II , respectively . This was specifically important in the 25 patients less than 60 years old ( 3-year relapse risk , 25 % v 83 % ; P = .01 ) . The 5-year overall survival ( OS ) was 36 % . Age ( < 60 v > or = 60 years ) was the only predictor for OS in the multivariate analysis ( relative risk , 2.1 ; 95 % confidence interval , 1.4 to 2.8 ) . RT dose was the only predictor of OS in patients younger than 60 years old who achieved CR at the end of all treatment ( 3-year OS , 92 % v 60 % for patients receiving 45 or 30.6 Gy , respectively ; P = .04 ) . CONCLUSION Reduction of the RT dose from 45 Gy to 30.6 Gy in patients younger than 60 years old with PCNSL who achieved CR result ed in an increased risk of relapse and lower OS Between 1983 and 1987 the Radiation Therapy Oncology Group conducted a prospect i ve phase II study to evaluate survival in primary non-Hodgkin 's lymphoma of the brain treated with whole brain irradiation to 40 Gy and a 20 Gy boost to tumor plus a 2 cm margin . Forty-one patients are reported . Full follow-up is available on 35/41 who have died . Six are alive at 8.8 - 67.2 months from start of radiation therapy with a median followup of 53.9 months . Overall median survival was 11.6 months from start of radiation therapy and 12.2 months from diagnosis , with 48 % surviving 1 year and 28 % surviving 2 years . Karnofsky Performance Status and age were significant prognostic factors . Patients with a Karnofsky Performance Status of 70 - 100 had a median survival of 21.1 months compared to 5.6 months for patients with a status of 40 - 60 ( p less than .001 ) . Fourteen patients less than 60 years of age had a median survival of 23.1 months , while 27 patients greater than or equal to 60 years of age had a median survival of 7.6 months ( log-rank p = .001 ) . Disease recurred in the brain in 25/41 ( 61 % ) of the patients , ( 21/41 in the brain only and 4/41 in the brain plus distant metastases ) . Despite high dose and large volume irradiation , primary Central Nervous System lymphoma still exhibits excessive mortality , especially in older patients . This paradox of the relative radioresistance of primary Central Nervous System lymphoma remains unresolved Primary CNS lymphoma ( PCNSL ) is a potentially curable brain tumor or at least one in which durable remission can be achieved . We report follow-up study results from NABTT 96 - 07 , a phase II multicenter trial in which 25 HIV-negative adult patients with newly diagnosed PCNSL were treated with 8 g/m2 of methotrexate IV every 2 weeks until a complete response ( CR ) , as determined by radiographic criteria , was achieved or a maximum of eight induction doses was reached.1 For patients achieving a CR , two consolidation cycles were administered every 14 days followed by 11 maintenance cycles ( 28 days each ) . We report up date d results of NABTT 96 - 07 after a minimum of 6.5 years of follow-up . Twelve of the original 25 patients ( 52 % ) achieved a CR to methotrexate induction . Five of these 12 patients ( 40 % ) who achieved CR have not relapsed after a median follow-up of 6.8 years . Eleven patients died of progressive disease or unknown cause and 3 died from other medical illnesses ( 2 with cardiac disease , 1 with septic arthritis ) for a total of 14 |
13,531 | 22,768,469 | In select patients , IPC use may provide an acceptable home-based treatment modality in addition to wearing compression garments | Intermittent pneumatic compression ( IPC ) therapy is an effective modality to reduce the volume of the lymphedematous limbs alone or in conjunction with other modalities of therapy such as decongestive therapy .
However , there is no consensus on the frequency or treatment parameters for IPC devices . | AIM The aim of this study was to review published literature concerning the use of compression treatments in the management of venous and lymphatic diseases and establish where reliable evidence exists to justify the use of medical compression and where further research is required to address areas of uncertainty . METHODS The authors search ed medical literature data bases and review ed their own collection s of papers , monographs and books for papers providing information about the effects of compression and r and omized clinical trials of compression devices . Papers were classified in accordance with the recommendations of the GRADE group to categorize their scientific reliability . Further classification was made according to the particular clinical problem that was addressed in the papers . The review included papers on compression stockings , b and ages and intermittent pneumatic compression devices . RESULTS The International Compression Club met once in Vienna and corresponded by email in order to reach an agreement of how the data should be interpreted . A wide range of compression levels was reported to be effective . Low levels of compression 10 - 30 mmHg applied by stockings are effective in the management of telangiectases after sclerotherapy , varicose veins in pregnancy , the prevention of edema and deep vein thrombosis ( DVT ) . High levels of compression produced by b and aging and strong compression stockings ( 30 - 40 mmHg ) are effective at healing leg ulcers and preventing progression of post-thrombotic syndrome as well as in the management of lymphedema . In some areas no reliable evidence was available to permit recommendations of level of compression or duration of treatment . These included : management of varicose veins to prevent progression , following surgical treatment or sclerotherapy for varicose veins , and the level of compression required to treat acute DVT . CONCLUSION This review shows that whilst good evidence for the use of compression is available in some clinical indications , there is much still to be discovered . Little is know about dosimetry in compression , for how long and at what level compression should be applied . The differing effects of elastic and short-stretch compression are also little understood The application of intermittent pneumatic compression ( IPC ) as a part of complex decongestive physiotherapy ( CDP ) remains controversial . The aim of this study was to investigate whether the combination of IPC with manual lymph drainage ( MLD ) could improve CDP treatment outcomes in women with secondary lymphedema after breast cancer treatment . A r and omized study was undertaken with 13 subjects receiving MLD ( 60 min ) and 14 receiving MLD ( 30 min ) plus IPC ( 30 min ) followed by st and ardized components of CDP including multilayered compression b and aging , physical exercise , and skin care 10 times in a 2-week-period . Efficacy of treatment was evaluated by limb volume reduction and a subjective symptom question naire at end of the treatment , and one and two months after beginning treatment . The two groups had similar demographic and clinical characteristics . Mean reductions in limb volumes for each group at the end of therapy , and at one and two months were 7.93 % and 3.06 % , 9.02 % and 2.9 % , and 9.62 % and 3.6 % , respectively ( p < 0.05 from baseline for each group and also between groups at each measurement ) . Although a significant decrease in the subjective symptom survey was found for both groups compared to baseline , no significant difference between the groups was found at any time point . The application of IPC with MLD provides a synergistic enhancement of the effect of CDP in arm volume reduction Background Prospect i ve investigations of complete decongestive lymphatic physiotherapy ( CDPT ) , including manual lymphatic drainage ( MLD ) , have vali date d the efficacy of these interventions for the initial reduction of edema and long-term maintenance of limb volume in lymphedema . However , CDPT dem and s substantial time and effort from patients to maintain these benefits ; the treatments are not always well-accepted , and patients may suffer from a deterioration in quality -of-life or a time-dependent loss of initial treatment benefits . A new device design ed for home use by the patient , the Flexitouch ™ , has been developed to mechanically simulate MLD . We have undertaken a prospect i ve , r and omized , crossover study of the efficacy of the Flexitouch ™ , when compared to massage , in the self-administered maintenance therapy of lymphedema . Methods A prospect i ve , r and omized , crossover study of maintenance therapy was performed in 10 patients with unilateral breast cancer-associated lymphedema of the arm . Each observation phase included self-administered treatment with the Flexitouch ™ or massage , 1 hour daily for 14 days , respectively , followed by crossover to the alternate treatment phase . Each treatment phase was preceded by a 1 week treatment washout , with use of garment only . The sequence of treatment was r and omly assigned . The potential impact of treatment modality on quality of life was assessed with serial administration of the SF-36 . Results Statistical analysis disclosed that the order of treatment had no outcome influence , permitting 10 comparisons within each treatment group . Post-treatment arm volume reduced significantly after the Flexitouch ™ , but not after self-administered massage . The patients ' mean weight decreased significantly with Flexitouch ™ use , but not with massage . The Flexitouch ™ device was apparently well-tolerated and accepted by patients . Serial SF-36 administration showed no deterioration in physical or psychosocial scores compared to baseline measurements ; there were no statistical differences in scores when the two treatment modalities were compared . Conclusion This short-term prospect i ve evaluation of the Flexitouch ™ suggests that the device may provide better maintenance edema control than self-adiminstered massage in breast cancer-associated lymphedema . The apparent ease of use and reliability of response to the device suggest that further broad-scale testing is warranted PURPOSE A prospect i ve evaluation was undertaken to assess the efficacy of intensive , short-term decongestive lymphatic therapy coupled with focused patient instruction in long-term self-care for the management of lymphedema . METHODS The therapeutic responses of 79 patients with lymphedema were analyzed prospect ively . Each patient received intensive , short-term decongestive lymphatic therapy , with quantification of the extent and durability of the clinical response . Decongestive lymphatic therapy was performed by therapists trained in these techniques . The mean ( + /-SD ) duration of therapy was 8+/-3 days . Instruction in self-management techniques was incorporated into the therapeutic regimen by day 3 of the patient 's treatment . The mean period of follow-up was 38+/-52 days . Changes in the volume of the affected limb were assessed with a geometric approximation derived from serial measurements of circumference along the axis of the limb . RESULTS The mean short-term reduction in limb volume was 44%+/-62 % of the excess volume in the upper extremities and 42%+/-40 % in the lower extremities . At follow-up , these results were adequately sustained : mean long-term excess volume reductions of 38%+/-56 % ( upper extremities ) and 41%+/-27 % ( lower extremities ) were observed . CONCLUSION Decongestive lymphatic therapy , combined with long-term self-management , is efficacious in treating patients with lymphedema of the extremity Sequential Intermittent Pneumatic Compression ( SIPC ) is an accepted method for treatment of peripheral lymphedema . This prospect i ve study evaluated the effect in 11 patients of a single session of SIPC on both lymphedema volume of the leg and isotope lymphography ( 99Tc dextran ) before SIPC ( control ) and 48 hours later after a 3 hour session of SIPC . Qualitative analysis of the 2 lymphoscintigrams ( LS ) was done by image interpretation by 3 physicians on a blind study protocol . The LS protocol attributed an index score based on the following variables : appearance , density and number of lymphatics , dermal backflow and collateral lymphatics in leg and thigh , visualization and intensity of popliteal and inguinal lymph nodes . Volume of the leg edema was evaluated by measuring limb circumference before and after SIPC at 6 design ated sites . Whereas there was a significant reduction of circumference in the leg after SIPC ( p<0.05 ) , there was no significant difference in the index scores of the LS before and after treatment . This acute or single session SIPC suggests that compression increased transport of lymph fluid ( i.e. , water ) without comparable transport of macromolecules ( i.e. , protein ) . Alternatively , SIPC reduced lymphedema by decreasing blood capillary filtration ( lymph formation ) rather than by accelerating lymph return thereby restoring the balance in lymph kinetics responsible for edema in the first place BACKGROUND Two phase II clinical studies used an experimental , multi-chambered compression device with different cuff pressure combinations in subjects with leg edema and chronic venous insufficiency . The objective of each study was to evaluate the safety and the relative effects of different cuff pressure combinations to determine if edema reduction was dose-dependent . METHODS Each study enrolled adults with chronic ( > or=6 weeks ) venous edema corresponding to CEAP C(3)-C(5 ) . The test device could apply different pressures at the foot , gaiter , mid-calf , and upper-calf . In the first study , the following six sustained pneumatic compression ( SPC ) profiles were applied for six hours each : 20 , 30 , and 40-mm Hg at the gaiter with graduated SPC ( ie , lower pressures at the calf ) ; and 20 , 30 , and 40-mm Hg at the gaiter with nongraduated SPC ( ie , the same pressures at the calf ) . In the second study , the following three intermittent pneumatic compression ( IPC ) profiles were applied for two hours each : 40 , 50 , and 60-mm Hg at the gaiter with graduated IPC ( ie , lower pressures at the calf ) . Each study included a baseline profile with no compression and two-day intervals between profiles . Leg volume was measured before and after compression using the water-displacement method . RESULTS A dose-response relationship was observed between increased SPC/IPC pressures and reduced limb edema . Limb volume was reduced most effectively with the highest pressures of 40-mm Hg nongraduated SPC and 60-mm Hg graduated IPC ( 136 mL and 87 mL , respectively ) ; however , some subjects reported discomfort with these profiles . Limb volume was reduced by more than 100 mL with 30 to 40-mm Hg graduated SPC and by 69 mL with 50-mm Hg graduated IPC , and subjects rated these profiles as comfortable or very comfortable . Of the 28 study participants ( 12 SPC , 16 IPC ) , two subjects reported pain with 60-mm Hg IPC ; no other adverse events were reported with SPC or IPC . CONCLUSION Pneumatic compression was safe and well-tolerated , with a dose-response relationship between increased SPC/IPC pressures and reduced leg edema . To our knowledge , this is the first study to demonstrate a dose-relationship in compression therapy : higher pressures are associated with greater volume reduction in subjects with chronic venous edema The cycle time and number of chambers in the pneumatic sleeve may influence the outcome of lymphedema therapy with intermittent compression devices . The aim of our study was to assess efficacy of several commonly used different IPC protocol s on edema volume reduction in women with postmastectomy lymphedema . Fixty-seven ( 57 ) women with secondary arm lymphedema ( age 39 - 80 ) were selected to the study . Women were r and omly assigned to two study groups with different IPC cycle times : I--90:90s and II--45:15s . Both groups were then r and omly divided into two subgroups with different sleeves : A--1 chamber sleeve ( 28 women ) and B--3 chamber sleeve ( 29 women ) . All women underwent IPC treatment for 5 weeks , 5 times a week for 1 hour ( 25 sessions ) . Arm volume measurements were performed before and after each IPC session . Significant reduction of edema volume was observed in all therapeutic subgroups , regardless of cycle times and number of chambers . In the group with short IPC cycle , better efficacy was noticed with 3-chamber sleeve . IPC is an effective method of volume reduction in women with postmastectomy arm lymphedema regardless of cycle times and number of sleeve chambers Acute ischaemia in the tibial compartments is a recognized complication of fractures , vascular injury , vascular surgery , crush injuries and burns . The tissue pressure was measured in the first week after injury and the effect of diuretics has been evaluated in a double-blind r and omized manner . The pressure in the anterior tibial compartment was measured in the first week after injury in a double-blind r and omized manner in 40 patients who had sustained either accidental or surgical injury of the leg . The pressure in the group treated with placebos increased by 20 per cent in the first 24 hours , whereas the pressure fell by 25 per cent in those treated with diuretics . Diuretic treatment is recommended for patients with injury of the lower limbs |
13,532 | 21,346,583 | The recommendations reported in the study are based on an extensive literature evaluation and were developed by considering the appropriateness of the choice of the imaging techniques while noninvasively detecting and characterizing focal liver lesions | OBJECTIVES To develop guidelines for the noninvasive imaging assessment of focal liver lesions comparing different imaging modalities focused on ( i ) evaluating the imaging techniques in terms of ( a ) diagnostic accuracy ; ( b ) role in the management of oncologic patients ; ( c ) follow-up of benign lesions ; and ( ii ) developing st and ard procedure for their use in patients with focal liver lesions that require targeted diagnostic characterization . | Abstract . The objectives of this study were twofold : ( a ) to assess safety and tolerability of the hepatobiliary MR contrast agent MnDPDP ; and ( b ) to investigate the sensitivity of MnDPDP-enhanced MRI , in comparison with dual-phase spiral CT , in the detection of hepatocellular carcinoma ( HCC ) in cirrhosis . Fifty patients with liver cirrhosis and histologically proven HCC were enrolled in a prospect i ve phase-IIIB clinical trial . All patients underwent evaluation with dual-phase spiral CT and pre-contrast and post-contrast MRI at 1.5 T. The MR examination protocol included spin-echo ( SE ) and gradient-recalled-echo ( GRE ) T1-weighted images acquired before and 60–120 min after administration of 0.5 μmol/kg ( 0.5 ml/kg ) MnDPDP ( Teslascan , Nycomed Amersham , Oslo , Norway ) ; and fast T2-weighted SE images obtained solely before contrast injection . Gold st and ard was provided by findings at Lipiodol CT in combination with follow-up spiral CT studies , which were repeated at 4-month intervals over a 10- to 27-month ( mean ± SD 20.1 ± 5.1 months ) follow-up period . No serious adverse event occurred . Eighty tumors ranging 0.8–9.1 cm in diameter ( mean ± SD 3.2 ± 2.4 cm ) were detected by Lipiodol CT or confirmed as cancerous foci by follow-up CT studies . Pre-contrast MRI detected 38 of 80 lesions ( 48 % ) ; MnDPDP-enhanced MRI , 65 of 80 lesions ( 81 % ) ; pre-contrast plus post-contrast MRI , 69 of 80 lesions ( 86 % ) ; and dual-phase spiral CT , 64 of 80 lesions ( 80 % ) . The difference between unenhanced and MnDPDP-enhanced MRI was statistically significant ( p < 0.001 ) . The difference between MRI ( pre-contrast plus post-contrast ) and dual-phase spiral CT was not statistically significant ( p = 0.33 ) . The confidence in the final diagnosis , however , was significantly higher for MRI as compared with spiral CT ( p < 0.001 ) . MnDPDP is a safe and well-tolerated hepatobiliary MR contrast agent . Magnetic resonance imaging with use of MnDPDP is significantly more sensitive than unenhanced MRI and as good as dual-phase spiral CT for detection of HCC in cirrhosis The purpose of this study was to evaluate the value of Ferumoxide-enhanced magnetic resonance ( MR ) imaging in the detection of hepatic metastases in high-risk patients treated for colorectal cancer that have rising CEA . We used 19 patients treated previously for colorectal cancer with rising CEA levels underwent an unenhanced T(1)-weighted ( T1W ) , T(2)-weighted ( T2W ) , STIR , and Ferumoxide-enhanced hepatic MRI . Following these studies , a laparotomy was performed and the liver was evaluated by palpation and intraoperative ultrasound . Two observers who were blinded to surgical results evaluated each MR sequence separately . The number of lesions considered highly suspicious for metastatic lesions were determined for each sequence and were compared to the results of surgery . The McNemar test was used to compare the outcomes of the different sequences . MR Imaging was unable to detect small ( < 5 mm ) metastases discovered at surgery . The best non-contrast sequences for detecting metastases were the STIR with 42 % sensitivity , 83 % specificity and an overall accuracy of 56 % and the T1W sequence ( sensitivity 38 % , specificity 100 % , accuracy 57 % ) , which were not significantly different ( p 0.4 ) . The noncontrast T2W sequence had a sensitivity of 29 % and a specificity of 77 % with an overall accuracy of 46 % . When all pre contrast scans were grouped together the common sensitivity was 42 % , specificity was 77 % and accuracy was 54 % . The post-ferumoxide T(2)W scans had a sensitivity of 42 % , specificity of 85 % , and accuracy of 57 % , but did not detect any additional lesions . There was no statistical difference between the pre- and post-contrast studies with regard to identifying patients with metastatic disease ( p 0.1 ) . In conclusion , we found small hepatic metastases in patients with early signs of recurrent colorectal cancer are difficult to detect on MRI . Ferumoxide-enhanced MRI was unable to detect additional hepatic metastases and performed no better than unenhanced MRI in detecting small hepatic metastasis The purpose of this study was to compare the diagnostic accuracy of contrast-enhanced ultrasound ( CEUS ) with spiral computed tomography ( SCT ) for the characterization of focal liver lesions ( FLL ) and to determine the degree of correlation between the two techniques . Seventy-seven FLL ( 45 hepatocellular carcinomas ; 12 metastases ; ten hemangiomas ; two regenerating/dysplastic nodules ; eight focal nodular hyperplasias ) detected with ultrasound ( US ) were prospect ively evaluated by CEUS using a second-generation contrast agent and SCT ( with an interval of no more than one month between the two techniques ) . Independent observers made the most probable diagnosis and the results were compared with the final diagnoses ( histology n = 59 ; MRI n = 18 ) . Statistical analysis was performed by the Chi-square and Kappa tests . CEUS provided a correct , specific diagnosis in 69/77 ( 90 % ) of the FLL , while SCT did so in 67/77 ( 87 % ) . The sensitivity , specificity , and diagnostic accuracy for malignancy were 91 % , 90 % , and 91 % , respectively , for CEUS and 88 % , 89 % , and 88 % , respectively , for SCT . No statistically significant difference was found between CEUS and SCT in the characterization of FLL ( p > 0.05 ) . In addition , agreement between the two imaging techniques was good ( k = 0.75 ) . We conclude that CEUS and SCT provide a similar diagnostic accuracy in the characterization of FLL , with a good degree of correlation between the two techniques PURPOSE To qualitatively and quantitatively evaluate the diagnostic efficacy of the breath-hold magnetic resonance ( MR ) imaging sequences in widespread clinical use for detection and characterization of focal hepatic lesions . MATERIAL S AND METHODS Fifty patients with 143 lesions [ 57 hepatocellular carcinomas ( HCC ) , 10 borderline lesions , 18 metastatic tumors , 21 hemangiomas , and 37 cysts ] underwent single-shot fast spin echo ( SSFSE ) , fast spin echo ( FSE ) , and gadolinium-enhanced dynamic fast spoiled gradient-recalled acquisition in steady state ( FSPGR ) breath-hold MR imaging of the liver . Alternative free receiver operating characteristic ( AFROC ) analysis was performed to independently and prospect ively assess each sequence . RESULTS For solid lesions , dynamic FSPGR allowed the most sensitive lesion detection and produced the highest lesion conspicuity and lesion-liver contrast-to-noise ratio ( CNR ) . For non-solid benign lesions , SSFSE and FSE produced better results than dynamic FSPGR . SSFSE allowed the most sensitive detection and produced the best lesion conspicuity and lesion-liver CNR . CONCLUSION SSFSE and dynamic FSPGR comprise the optimal imaging protocol for breath-hold MR assessment of focal hepatic lesions . This combination of sequences allows acquisition of critical diagnostic information about both inherent T2 and T1 lesion contrast and lesion vascularity Purpose The purpose of the study was to introduce our protocol for contrast-enhanced multiphase dynamic ultrasonography ( US ) and examine the effectiveness of this method for characterizing liver tumors . Methods The subjects were 142 patients with liver tumors . The final diagnoses were 58 hepatocellular carcinomas ( HCCs ) , 4 cholangiocellular carcinomas ( CCCs ) , 14 metastases , 29 hemangiomas , 6 cases of focal nodular hyperplasia ( FNH ) , and 31 other benign lesions . The contrast agent used was Levovist . A wide-b and pulse inversion harmonic imaging mode was employed . Multiphase dynamic US was achieved by changing the sound transmission interval automatically from 0.3 s to 15.0 s according to a preset menu . Early arterial-phase images were observed at the short interval , and an equilibrium-phase image was observed at the longest interval . After a series of vascular images , a postvascular liver parenchymal image was obtained . Based on previously published criteria , the most compatible diagnosis was noted . The accuracy of this multiphase dynamic US technique for diagnosing focal liver lesions was examined by comparing our results with the final diagnosis based on a prospect i ve study . Results The overall accuracy of all 142 cases was 93.7 % . The sensitivity , specificity , and positive predictive value were , respectively , 100 % , 92.9 % , and 90.6 % for HCC ; 88.9 % , 97.6 % , and 84.2 % for metastasis or CCC ; 89.7 % , 100 % , and 100 % for hemangioma ; and 83.3 % , 100 % , and 100 % for FNH . Conclusion Contrast-enhanced multiphase dynamic US is a highly accurate , safe diagnostic tool for characterizing liver tumors Background : Hepatocellular carcinoma ( HCC ) is often detected at a relatively late stage when tumour size prohibits curative surgery . Screening to detect HCC at an early stage is performed for patients at risk . Aim : The aim of this study was to compare prospect ively the diagnostic accuracy and classification for management of the two state of the art secondline imaging techniques : triphasic spiral computer tomography ( CT ) and super paramagnetic iron oxide ( SPIO ) enhanced magnetic resonance imaging ( MRI ) . Patients : Sixty one patients were evaluated between January 1996 and January 1998 . Patients underwent CT and MRI within a mean interval of 6.75 days . Methods : CT and MRI were evaluated blindly for the presence and number of lesions , characterisation of these lesions , and classification for management . For comparison of the data on characterisation , the CT and MRI findings were compared with histopathological studies of the surgical specimens and /or follow up imaging . Data of patients not lost to follow up were available to January 2001 . Results : SPIO enhanced MRI detected more lesions and overall smaller lesions than triphasic spiral CT ( number of lesions 189 v 124 ; median diameter 1.0 v 1.8 cm ; Spearman rank 's correlation coefficient 0.63 , p<0.001 ) . There was no significant difference in accuracy between CT and MRI for lesion characterisation . The agreement in classification for management was very good ( weighted kappa 0.91 , 95 % CI 0.83–0.99 ) . Conclusion : SPIO enhanced MRI detects more and smaller lesions , but both techniques are comparable in terms of classification for management . SPIO enhanced MRI may be preferred as there is no exposure to ionising radiation Background : In recent years , liver transplantation in patients with hepatocellular cancers and cirrhosis has been restricted to those with small cancers ( < 5 cm for solitary and <3 cm for multifocal HCC with <3 nodules ) . The selection of patients for liver transplantation is based on pre-operative imaging . The accuracy of imaging correlated with explant histology and the effect of tumour stage has not been evaluated in this selected population . Methods : In this study , prospect ively collected data for 30 patients who underwent orthotopic liver transplantation for cirrhosis complicated by small hepatocellular carcinoma ( HCC ) at a single centre have been review ed with the aim of correlating radiological findings , explant histology and patient outcome . Patients who underwent orthotopic liver transplantation between 1995 and 1999 had plain and contrast-enhanced dual-phase spiral CT ( DCT ) scans of the liver . Patients suspected of having HCC on CT scan or due to elevated serum alpha-fetoprotein underwent iodized oil CT ( IOCT ) . Following transplantation , the explanted liver was serially sectioned at 10-mm intervals and examined by a pathologist blinded to the results of imaging . Data collected prospect ively on imaging and histology were compared with outcome data . The median period of follow-up was 1,139 days ( range 690–1,955 days ) after transplantation . All patients were followed up by clinical assessment , assessment of serum alpha-protein levels and imaging when indicated . Results : All the patients transplanted fulfilled the selective criteria on the basis of imaging ( solitary HCC < 5 cm in diameter or multifocal HCC <3 cm in diameter with <3 nodules ) . Of the 30 patients transplanted , 46 HCCs were detected on explant histology with a median size of 24 mm ( range 6–75 mm ) . Ten patients had multifocal disease ( median number of lesions 2 , range 2–4 ) . No significant difference was observed between IOCT and DCT with regards to the sensitivity ( 67.4 vs. 68 % ) and specificity ( 78.97 vs. 88.6 % ) of detecting HCCs . IOCT had a positive predictive value of 78.9 % as compared to 82.8 % for DCT . IOCT had an overall sensitivity of 40 % as compared to 30 % for DCT in detecting multifocal disease ( not significant ) . Histological assessment of the explanted livers showed that 8 patients had well- , 17 moderate and 5 poorly differentiated HCCs . Tumour size and the presence of multifocal disease did not influence survival in this study . Microvascular invasion was more common with larger tumours ( from 38 % with lesions less than 40 mm in diameter to 60 % with lesions > 40 mm in diameter ; p < 0.01 ) and with moderately ( 29.4 % ) or poorly differentiated ( 60 % ) HCCs than well-differentiated HCC ( 12.5 % ) ( p < 0.04 and 0.01 for well- vs. moderately and poorly differentiated HCC , respectively ) . Microvascular invasion on explant histology was associated with poor survival . Of the 17 transplant recipients without vascular invasion , 15 were alive at 1 and 2 years in comparison to 7 of 9 with microscopic vascular invasion ( p < 0.01 ) . Four patients died in the post-transplant period due to recurrent HCC . Overall survival [ after excluding early post-transplant sepsis-induced deaths ( n = 4 ) ] at 1 year was 83.3 % . Conclusions : Selective criteria for transplantation of HCC in cirrhosis are associated with a 1-year and 3-year survival rate of 73.3 % ( including early post-transplant sepsis-induced deaths ) . IOCT and DCT are similar in their ability to detect unifocal or multifocal HCC . Tumour size and number are not predictive of recurrence with these selective criteria , but microscopic vascular invasion is a bad prognostic factor AIM To assess the vascularity of hepatocellular carcinoma ( HCC ) before and after transcatheter arterial chemoembolization ( TACE ) with the quantitative parameters obtained by first pass perfusion weighted MR imaging ( FP-MRI ) . METHODS Seventeen consecutive patients with one to three lesions in liver underwent FP-MRI before treatment . FP-MRI was also performed one , three , six , nine months , and one year after TACE . The baseline signal intensity ( S0 ) of pre-TACE and one month after TACE was analyzed , the vascularity of HCC assessed by steepest slope of the signal intensity versus time curves ( SS ) was blindly correlated with their DSA feature and clinical outcome . RESULT No significant difference was found on baseline signal intensity ( S0 ) between pre-TACE and one month after TACE ( F=0.309 , P=0.583 ) , The SS ( mean , 32 % per second ) of lesion one month after TACE was lower than that of pre-TACE ( mean , 69 % per second ) , but with no statistical significance ( F=3.067 , P=0.092 ) . When local recurrence occurred , the time intensity curves became steeper . The vascularity of HCC before and after TACE grade d by SS closely correlated with that by DSA ( K=0.453 , P<0.05 ) . CONCLUSION FP-MRI is a useful criterion for selecting effective interventional treatment for patients with HCC in their initial treatment and during follow up PURPOSE To determine the accuracy for detection and characterization of focal hepatic lesions of nonenhanced , superparamagnetic iron oxide (SPIO)-enhanced , or a combination of nonenhanced and SPIO-enhanced MR imaging and contrast-enhanced spiral computed tomography ( CT ) . MATERIAL S AND METHODS Spiral CT and T2-weighted SPIO-enhanced ( ferucarbotran-enhanced ) MR imaging were performed in 35 patients within 2 weeks before surgery for malignant hepatic lesions . Only malignant lesions with histopathologic proof were considered . A total of 875 images with and 800 images without focal lesions were presented to five readers , who were asked to assess the presence and characterization of lesions by using a five-point confidence scale . Receiver operating characteristic analysis was performed . RESULTS Nonenhanced and SPIO-enhanced images together and SPIO-enhanced images alone yielded the best performance for lesion detection . No differences were found among all imaging techniques with regard to lesion characterization ( benign vs malignant ) . The combined approach result ed in larger area under the ROC curve ( A(z ) = 0.9062 ) and accuracy ( 85.3 % ) ( P < 0.02 ) , as compared with SPIO-enhanced MR imaging ( A(z ) = 0.8667 ; accuracy , 73.1 % ) . CONCLUSION SPIO-enhanced T2-weighted MR imaging was more accurate than nonenhanced T1-weighted and T2-weighted MR imaging and contrast-enhanced spiral CT for the detection of focal hepatic lesions . The combined analysis of nonenhanced and SPIO-enhanced images was more accurate in the characterization of focal hepatic lesions than was review of SPIO-enhanced images alone Objective To determine the real value of liver imaging in cirrhosis by macro- and histomorphologic examination of the entire organ after orthotopic liver transplantation for hepatocellular carcinoma ( HCC ) . Summary Background Data In comparative studies , a virtual sensitivity of up to 94 % is described for helical computed tomography in HCC staging . The tumor detection rate of intraoperative ultrasonography ( IOUS ) is reported to be almost 100 % . Methods This prospect i ve observational study comprised 23 patients with HCC in cirrhosis admitted for orthotopic liver transplantation . Results of preoperative triphasic helical computed tomography ( HCT ) and IOUS were correlated with histopathologic results after 3-mm-slicing of the explanted liver . Results Overall , 179 liver segments were examined by HCT , IOUS , and MHM . Fifty-two malignant lesions and 10 dysplastic nodules were revealed by MHM . Using HCT , 13 HCCs could not be identified in 8 patients and 15 results were falsely positive in 10 patients . The detection rate of dysplastic nodes was 40 % for HCT and 60 % for IOUS . IOUS missed four HCCs in four patients and had six false-positive results in six patients . In a segment-based analysis , the overall accuracy of IOUS was significantly higher for IOUS ( 95.5 % ) versus HCT ( 89.9 % ) . In the lesion-by-lesion analysis , the sensitivity was 92.3 % for IOUS and 75.0 % for HCT , with a significant difference . Conclusions Correlation of explanted liver pathologic results offers precise evaluation of imaging modalities . The data of this histopathologically based study confirm that IOUS is significantly superior in staging HCC in cirrhosis versus CT , even after technical refinements through enhanced multiphasic high-velocity helical scanning OBJECTIVE Our objectives were to propose and evaluate a dynamic sonography protocol for the characterization of hepatic tumors . SUBJECTS AND METHODS The subjects were 107 patients with focal liver lesions that initially had been found on conventional sonograms . The final diagnoses for the lesions were hepatocellular carcinoma in 60 patients , cholangiocellular carcinoma in six , metastatic carcinoma in 24 , hemangioma in 10 , and focal fat-spared region in seven . The pulse inversion harmonic imaging mode and a galactose-based contrast agent ( Levovist ) were used . Dynamic sonography was design ed to obtain vascular-phase ( composed of the arterial phase and the portal phase ) images of the focal lesion and liver-parenchymal-phase images of the whole liver in a series obtained after a bolus injection of the contrast agent . RESULTS If the whole-tumor or mosaic enhancement patterns ( arterial phase ) and /or the reticular enhancement ( parenchymal phase ) are regarded as positive findings for hepatocellular carcinoma , the sensitivity , specificity , and positive predictive value of dynamic sonography in our study were 92 % , 96 % , and 96 % , respectively . If a ring enhancement ( arterial to portal phase ) or a clear defect ( parenchymal phase ) or both are regarded as positive findings for cholangiocellular carcinoma or metastasis , the sensitivity , specificity , and positive predictive value were 90 % , 95 % , and 88 % , respectively . If puddle enhancement ( portal phase ) is regarded as a positive finding for hemangioma , the figures for sensitivity , specificity , and positive predictive value were 60 % , 100 % , and 100 % , respectively . Also , the tumors that showed no focal sign in the liver parenchymal phase were all benign lesions , such as hemangiomas or focal fat-spared regions . CONCLUSION Dynamic sonography in a protocol combining pulse inversion harmonic imaging and an IV bolus injection of the contrast agent proved to be an effective tool in characterizing liver tumors PURPOSE To evaluate whether mangafodipir trisodium (Mn-DPDP)-enhanced magnetic resonance ( MR ) imaging surpasses dual-phase spiral computed tomography ( CT ) in differentiating focal liver lesions . MATERIAL S AND METHODS One hundred forty-five patients who had or were suspected of having focal liver lesions were included in a multicenter study and underwent dual-phase spiral CT and enhanced MR imaging . Image interpretations performed by independent experienced radiologists were compared with the final diagnosis that was based on all available clinical information ( including histopathologic findings in 77 patients ) and that was determined with consensus . Differences in classifications by using either enhanced MR imaging or dual-phase spiral CT were analyzed with the McNemar test , and receiver operating characteristic ( ROC ) curves were used to compare the diagnostic performance of enhanced MR imaging and dual-phase spiral CT . RESULTS Lesion classification was correct in 108 ( 74 % ) patients with enhanced MR imaging and in 83 ( 57 % ) with dual-phase spiral CT ( P = .001 ) . Lesions were correctly classified as either malignant or benign in 123 ( 85 % ) patients with enhanced MR imaging and in 98 ( 68 % ) with dual-phase spiral CT ( P = .001 ) . Classification of lesions as either hepatocellular or nonhepatocellular was correct in 130 ( 90 % ) patients with enhanced MR imaging and in 93 ( 64 % ) with dual-phase spiral CT ( P = .001 ) . These differences remained when analyses were restricted to histopathologically confirmed diagnoses . Comparison of the ROC curves illustrated that enhanced MR imaging performance surpassed that of dual-phase spiral CT . CONCLUSION Mn-DPDP-enhanced MR imaging is superior to dual-phase spiral CT in classification of focal liver lesions PURPOSE To compare the performance of dynamic gadolinium-enhanced and ferumoxides-enhanced MRI in the detection and characterization of hepatic lesions , on 1.5-T and 0.2-T magnets MATERIAL S AND METHODS In 41 patients ( 23 men , 18 women ) , 52 hepatic MR examinations were performed and retrospectively analyzed ; 39 and 13 examinations were performed on 1.5-T and 0.2-T magnets , respectively . A total of 33 of 41 patients had known malignancies , and 31 of 33 patients had biopsy of at least one lesion . First , a combination of unenhanced T2-weighted sequences and gradient-echo T1-weighted sequences were performed . Then , dynamic gadolinium-enhanced ( 0.1 mmol/kg ) T1 GRE sequences were obtained , followed by intravenous drip infusion of ferumoxides ( 10 micromol/kg ) . The T2-weighted sequences were then repeated . The unenhanced and gadolinium-enhanced images ( the Gd set ) were review ed separately from the unenhanced and ferumoxides-enhanced images ( the ferumoxides set ) by two abdominal imagers . The review ers were blinded to clinical history and review ed the individual studies in each set r and omly . Each detected lesion was scored on a five-point scale for characterization scores : nonsolid ( 1 or 2 ) , indeterminate ( 3 ) , or solid ( 4 or 5 ) . A consensus review was then performed correlating all available pathology , imaging , clinical findings , and follow-up to act as a gold st and ard . Receiver-operating-characteristic ( ROC ) curves were generated and both area-under-the-curve ( Az values ) and sensitivity values were calculated . Significance of Az and sensitivity differences was assessed using st and ard Z-test and chi-square . RESULTS Of 270 lesions detected by consensus , 211 were on 1.5-T and 59 were on 0.2-T scanners . The accuracy ( Az values ) of lesion detection overall , of both readers , was greater for the ferumoxides set than for the Gd set ( reader 1 : 0.95 vs. 0.89 ( P < 0.05 ) ; reader 2 : 0.91 vs. 0.78 ( P < 0.05 ) ) . Az values for both readers were greater on the ferumoxides set for both the 1.5-T scans and the 0.2-T scans . Out of 270 lesions detected , 231 were characterized by consensus review as solid ( 185 ) or nonsolid ( 46 ) . There was a significant improvement in lesion characterization for both readers on the GD set compared with the ferumoxides set on both high and low field scanners ( Az reader 1 : 0.99 vs. 0.96 ( P < 0.05 ) ; Az reader 2 : 0.99 vs. 0.95 ( P < 0.05 ) ) , respectively . CONCLUSION At both 1.5-T and 0.2-T , ferumoxides-enhanced sequences were better for lesion detection , while gadolinium-enhanced sequences were better for lesion characterization , respectively This study prospect ively evaluates the accuracy of contrast-enhanced ultrasound ( CEUS ) and dynamic magnetic resonance imaging ( MRI ) for the diagnosis of nodules 20 mm or smaller detected during ultrasound ( US ) surveillance . We included 89 patients with cirrhosis [ median age , 65 years ; male 53 , hepatitis C virus 68 , Child-Pugh A 80 ] without prior hepatocellular carcinoma ( HCC ) in whom US detected a small solitary nodule ( mean diameter , 14 mm ) . Hepatic MRI , CEUS , and fine-needle biopsy ( gold st and ard ) ( FNB ) were performed at baseline . Non-HCC cases were followed ( median 23 months ) by CEUS/3 months and MRI/6 months . FNB was repeated up to 3 times and on detection of change in aspect/size . Intense arterial contrast uptake followed by washout in the delayed/venous phase was registered as conclusive for HCC . Final diagnoses were : HCC ( n = 60 ) , cholangiocarcinoma ( n = 1 ) , and benign lesions ( regenerative/dysplastic nodule , hemangioma , focal nodular hyperplasia ) ( n = 28 ) . Sex , cirrhosis cause , liver function , and alpha-fetoprotein ( AFP ) levels were similar between HCC and non-HCC groups . HCC patients were older and their nodules significantly larger ( P < 0.0001 ) . First biopsy was positive in 42 of 60 HCC patients . Sensitivity , specificity , and positive and negative predictive values of conclusive profile were 61.7 % , 96.6 % , 97.4 % , and 54.9 % , for MRI , 51.7 % , 93.1 % , 93.9 % , and 50.9 % , for CEUS . Values for coincidental conclusive findings in both techniques were 33.3 % , 100 % , 100 % , and 42 % . Thus , diagnosis of HCC 20 mm or smaller can be established without a positive biopsy if both CEUS and MRI are conclusive . However , sensitivity of these noninvasive criteria is 33 % and , as occurs with biopsy , absence of a conclusive pattern does not rule out malignancy . These results vali date the American Association for the Study of Liver Disease ( AASLD ) guidelines AIM To evaluate the characterization of liver hemangiomas and malignant tumors using power Doppler sonography before and after intravenous injection of a sonocontrast agent . METHODS Forty-five patients with 57 liver tumors ( 22 hemangiomas , 24 metastases , 10 hepatocellular carcinomas ( HCC ) and one cholangiocellular carcinoma ) were examined prospect ively . The distribution ( peripheral , central , mosaic ) and extent ( none , minimal , moderate and strong ) of intratumoral flow pattern in each sonographic examination was subjectively classified . RESULTS The administration of the sonocontrast agent by bolus injection caused enhancement to gradually increase up to 2 min and lasted for 4 - 5 min . After injection of contrast agent , flow signals appeared or increased in 34 tumors . No signal enhancement was observed in 18 hemangiomas , four metastases and one HCC . The sensitivity and specificity of intratumoral vascularity for the detection of malignant liver tumors was 37.1 and 90.9 % for unenhanced power Doppler sonography , and 85.7 and 81.8 % for contrast-enhanced power Doppler sonography , respectively . CONCLUSION Contrast-enhanced power Doppler sonography is superior to unenhanced power Doppler sonography in the demonstration of malignant tumor vascularity , and is helpful in differentiating between hemangiomas and malignant liver tumors . A specific flow pattern within the tumor is not established in primary and metastatic malignant tumors with contrast-enhanced power Doppler sonography OBJECTIVE We investigated the ability of contrast-enhanced sonography with SonoVue ( Altana Pharma , Konstanz , Germany ) , a sulfur hexafluoride microbubble contrast agent , to reveal differences between benign and malignant focal hepatic lesions . METHODS One hundred twenty-six lesions in 124 patients with focal hepatic lesions detected by B-mode sonography ( hepatocellular carcinoma , n = 36 ; metastasis , n = 25 ; cholangiocellular carcinoma , n = 1 ; lymphoma , n = 2 ; focal nodular hyperplasia , n = 9 ; adenoma , n = 4 ; regenerative cirrhotic nodule , n = 13 ; hemangioma , n = 29 ; and focal hyposteatosis , n = 7 ) were examined in a prospect i ve study . After intravenous injection of 2.4 mL of SonoVue , the liver was examined continuously for 3 minutes by low-mechanical index pulse inversion sonography . RESULTS For the discrimination of malignant versus benign liver lesions , SonoVue-enhanced sonography improved sensitivity from 78 % to 100 % and specificity from 23 % to 92 % compared with baseline sonography . Receiver operating characteristic analysis revealed a significant improvement in this discrimination ( area under the receiver operating characteristic curve , 0.510 + /- 0.054 [ SD ] at baseline sonography , 0.998 + /- 0.003 with SonoVue-enhanced sonography ; P < .001 ) . The following flow patterns in the early phase were diagnosis specific : early central starlike pattern for focal nodular hyperplasia , peripheral globular-nodular pattern for hemangioma , and diffuse arterial enhancement for malignant lesions . Homogeneous enhancement in the late phase was predictive for benign lesions ( P < .001 ) . Conversely , 93 % of patients without contrast enhancement in the late phase had malignant lesions ( P < .001 ) . CONCLUSIONS SonoVue-enhanced sonography has greater specificity and sensitivity than baseline sonography for the differentiation of benign and malignant liver lesions OBJECTIVE The purpose of this study was to evaluate the diagnostic efficacy of three-phase helical dynamic CT in the detection and characterization of hepatocellular carcinomas and dysplastic nodules in cirrhotic livers . SUBJECTS AND METHODS Three-phase helical dynamic CT in 41 patients with liver cirrhosis was evaluated prospect ively before orthotopic liver transplantation . The numbers of hepatocellular carcinomas and dysplastic nodules were assessed in the explanted livers and compared with pretransplantation CT findings . RESULTS Examination of the explanted livers revealed 21 hepatocellular carcinomas in 15 patients and 23 dysplastic nodules in 10 patients . The size of the hepatocellular carcinomas was 0.6 - 5 . 0 cm ( mean , 1.9 cm ) , and that of the dysplastic nodules was 0.7 - 2.0 cm ( mean , 1.0 cm ) . The use of helical dynamic CT enabled detection of 15 of 21 hepatocellular carcinomas ( sensitivity , 71 % ) and nine of 23 dysplastic nodules ( sensitivity , 39 % ) . Patient sensitivity and specificity in the detection of hepatocellular carcinomas were 80 % ( 12/15 ) and 96 % ( 25/26 ) , respectively , and for dysplastic nodules , 50 % ( 5/10 ) and 97 % ( 30/31 ) , respectively . CONCLUSION Three-phase helical dynamic CT is relatively insensitive for detection of hepatocellular carcinomas and dysplastic nodules in cirrhotic livers , especially for dysplastic nodules and hepatocellular carcinomas smaller than 2 cm Noninvasive liver imaging has developed rapidly result ing in increased accuracy for detecting primary and secondary hepatic tumors . Intraoperative ultrasonography ( IOUS ) was commonly considered to be the gold st and ard for liver staging , but the current value of IOUS is unknown in view of more sophisticated radiologic tools . The purpose of this prospect i ve study was to evaluate the impact of IOUS on the treatment of 149 patients undergoing liver surgery for malignant disease ( colorectal metastasis , 61 patients ; hepatoma , 52 patients ; other hepatic malignant tumors , 36 patients ) . The sensitivities of computed tomography ( CT ) , helical CT , magnetic resonance imaging , and IOUS in patients with colorectal metastases were 69.2 % , 82.5 % , 84.9 % , and 95.2 % in a segment-by-segment analysis ; in patients with hepatoma their sensitivities were 76.9 % , 90.9 % , 93.0 % , and 99.3 % ; and in patients with other hepatic malignancies they were 66.7 % , 89.6 % , 93.3 % , and 98.9 % , respectively . Additional malignant lesions ( AMLs ) were first detected by inspection and palpation in 20 patients ( 13.4 % ) . In another 18 patients ( 12.1 % ) IOUS revealed at least one AML . Overall , the findings obtained only by IOUS changed the surgical strategy in 34 cases ( 22.8 % ) . It was concluded that IOUS , having undergone some refinement as well , still has immense diagnostic value in hepatectomy c and i date s. Frequently avoiding palliative liver resection and occasionally disproving unresectability as assessed by preoperative imaging , IOUS still has a significant impact on surgical decision making and should still be considered the gold st and ard . RésuméOn a récemment assisté à une amélioration importante dans la précision de la détection des tumeurs primitives et secondaires du foie par l’imagerie non-invasive . L’échographie peropératoire ( EPO ) a été considérée comme l’examen de référence ( « gold st and ard » ) dans le Staging du foie , mais la valeur de l’EPO est discutée à présent en raison de l’apparition d’investigations radiologiques plus sophistiquées . Le but de cette étude prospect i ve a été d’évaluer l’impacte de l’EPO au cours d’une résection hépatique pour maladie maligne chez 149 patients ( métastases d’origine colorectale : 61 patients ; carcinome hépatocellulaire : 52 patients ; autres tumeurs hépatiques malignes : 36 patients ) . Chez les patients ayant des métastases d’origine colorectale , la sensibilité de la tomodensitométrie simple ( TDM ) , de la tomodensitométrie hélicoïdale ( TDMh ) , de la résonance magnétique ( RM ) et l’EPO a été de 69.2 % , 82.5 % , 84.9 % et 95.2 % dans une analyse du foie segment par segment . Chez les patients porteurs de carcinome hépatocellulaire , la sensibilité de ces différentes méthodes était , respectivement , de 76.9 % , 90.9 % , 93 % et 99.3 % ; chez les patients ayant d’autres tumeurs malignes du foie , la sensibilité était , respectivement , de 66.7 % , 89.6 % , 93.3 % et 98.9 % . D’autres lésions malignes ont été détectées à l’inspection et à la palpation chez 20 patients ( 13.4 % ) . De plus , chez 18 autres patients ( 12.1 % ) , l’EPO a décelé au moins une lésion maligne supplémentaire . Globalement , les données obtenues par l’EPO ont changé la stratégie chirurgicale dans 34 cas ( 22.8 % ) . On conclue que l’EPO , grâce à quelques raffinements , a toujours une immense valeur diagnostique pour les c and idats à l’hépatectomie . En évitant à certains patients une résection palliative , et en permettant , de temps à autre , une résection jugée impossible par les investigations préopératoires , l’EPO garde un impacte significatif sur la décision chirurgicale et devrait continuer à être le « gold st and ard».ResumenEl rápido desarrollo de los métodos no invasivos ha conferido una mayor precisión diagnóstica de los tumores hepáticos tanto primarios como secundarios . La ecografÍa intraoperatoria ( IOUS ) se consideró como el mejor método diagnóstico para la estadificación hepática , pero en la actualidad , su valor está en entredicho ante los nuevos y sofisticados estudios radiológicos . El objetivo de este estudio prospect ivo fue evaluar el valor de la IOUS en el tratamiento quirúrgico de 149 pacientes con neoplasias malignas de hÍgado ( metástasis colorrectales n=61 ; hepatomas n=52 ; otros tumores hepáticos malignos n=36 ) . El análisis secuencial segmentario demostró en pacientes con metástasis colorrectales una sensibilidad para la tomografÍa axial o helicoidal computarizada ( CT y hCT ) del 69.2 % y 82.5 % , para la resonancia magnética nuclear ( MR ) del 84.9 % y para la IOUS del 95.2 % . En pacientes con hepatomas la sensibilidad de estos métodos fue del 76.9 % , 90.9 % , 93 % y 98.9 % . En 20 pacientes ( 13.4 % ) lesiones malignas adicionales ( AML ) se diagnosticaron por inspección y palpación . En otros 18 pacientes ( 12.1 % ) la IOUS fue capaz de detectar al menos una AML . En 34 casos ( 22.8 % ) el conjunto de hallazgos obtenidos exclusivamente con la IOUS propició un cambio de estrategia quirúrgica . En conclusión , la IOUS , con sus recientes mejoras , sigue teniendo un inmenso valor diagnóstico para aquellos que son c and idatos a una hepatectomÍa . Previene , con frecuencia , las resecciones hepáticas paliativas y , ocasionalmente , contradice el diagnóstico de irresecabilidad obtenido con otros medios diagnósticos . La IOUS sigue teniendo un importante valor a la hora de establecer una decisión quirúrgica y continúa siendo el mejor método diagnóstico In a prospect i ve study , we examined the impact of arterial hypervascularity , as established by the European Association for the Study of the Liver ( EASL ) recommendations , as a criterion for characterizing small ( 1‐3 cm ) nodules in cirrhosis . A total of 72 nodules ( 1‐2 cm , n = 41 ; 2.1‐3 cm , n = 31 ) detected by ultrasonography in 59 patients with cirrhosis were included in the study . When coincidental arterial hypervascularity was detected at contrast perfusional ultrasonography and helical computed tomography , the lesion was considered to be hepatocellular carcinoma ( HCC ) according to EASL criteria . When one or both techniques showed negative results , ultrasound‐guided biopsy was performed . In cases with negative results for malignancy or high‐ grade dysplasia , biopsy was repeated when an increase in size was detected at the 3‐month follow‐up examination . Coincidental hypervascularity was found in 44 of 72 nodules ( 61 % ; 44 % of 1‐2‐cm nodules and 84 % of 2‐3‐cm nodules ) . Fourteen nodules ( 19.4 % ) had negative results with both techniques ( hypovascular nodules ) . Biopsy showed HCC in 5 hypovascular nodules and in 11 of 14 nodules with hypervascularity using only one technique . All nodules larger than 2 cm finally result ed to be HCC . Not satisfying the EASL imaging criteria for diagnosis were 38 % of HCCs 1 to 2 cm ( 17 % hypovascular ) and 16 % of those 2 to 3 cm ( none hypovascular ) . In conclusion , the noninvasive EASL criteria for diagnosis of HCC are satisfied in only 61 % of small nodules in cirrhosis ; thus , biopsy frequently is required in this setting . Relying on imaging techniques in nodules of 1 to 2 cm would miss the diagnosis of HCC in up to 38 % of cases . Any nodule larger than 2 cm should be regarded as highly suspicious for HCC . ( HEPATOLOGY 2005 . PURPOSE To evaluate gadobenate dimeglumine ( Gd-BOPTA ) for dynamic and delayed magnetic resonance ( MR ) imaging of focal liver lesions . MATERIAL S AND METHODS In 126 of 214 patients , MR imaging was performed before Gd-BOPTA administration , immediately after bolus administration of a 0.05- mmol/kg dose of Gd-BOPTA , and 60 - 120 minutes after an additional intravenously infused 0.05-mmol/kg dose . In 88 patients , imaging was performed before and 60 - 120 minutes after a single , intravenously infused 0.1-mmol/kg dose . T1- and T2-weighted spin-echo and T1-weighted gradient-echo images were acquired . On-site and blinded off-site review ers prospect ively evaluated all images . Intraoperative ultrasonography , computed tomography ( CT ) during arterial portography , and /or CT with iodized oil served as the reference methods in 110 patients . RESULTS Significantly more lesions were detected on combined pre- and postcontrast images compared with on precontrast images alone ( P < . 01 ) . All review ers reported a decreased mean size of the smallest detected lesion and improved lesion conspicuity on postcontrast images . All on-site review ers and two off-site review ers reported increased overall diagnostic confidence ( P < .01 ) . Additional lesion characterization information was provided on up to 109 ( 59 % ) of 184 delayed images and for up to 50 ( 42 % ) of 118 patients in whom dynamic images were assessed . Gd-BOPTA would have helped change the diagnosis in 99 ( 47 % ) of 209 cases and affected patient treatment in 408 ( 23 % ) of 209 cases . CONCLUSION Gd-BOPTA increases liver lesion conspicuity and detectability and aids in the characterization of lesions Although previous studies have demonstrated the ability of ultrasonography ( US ) screening to detect small asymptomatic hepatocellular carcinoma ( HCC ) , the efficacy of US screening in reducing deaths from HCC still remained unresolved . A 2-stage screening program was design ed to identify a high risk group in 7 townships in Taiwan by 6 markers ( of risk for HCC ) and repeated US screening was further applied to those with at least 1 positive result for the 6 markers , with a range of 3- to 6-month inter-screening intervals to those with liver cirrhosis or other chronic liver diseases and an annual screening regime for the remaining subjects with normal findings according to US . The 4,843 subjects in this cohort were followed up for an average of 7 years . We compared 4,385 attenders with 458 non-attenders , in conjunction with baseline assessment for self- selection bias . In addition , we assessed baseline variables with respect to their effects on risk of incidence of and mortality from HCC and on risk of incidence of liver cirrhosis . The difference in mortality between attenders and non-attenders was then re-estimated adjusting for significant predictors of cirrhosis , HCC incidence and HCC death as a further guard against baseline differences between attenders and non-attenders in risk profiles . Results of US screening for this high risk group found the mortality was lower by 24 % ( 95 % CI : -52 to 62 % ) in the attenders compared to the non-attenders . After adjustment for sensitivity , the mean sojourn time ( MST ) were 1.57 ( 95 % CI : 0.94 - 4.68 ) for subjects with liver cirrhosis and 2.66 ( 95 % CI : 1.68 - 6.37 ) years for non-cirrhotic patient . Significant increases in risk of HCC incidence were associated with increasing age , male gender , hepatitis B surface antigen positive ( HbsAg ) , hepatitis C antibody positive ( Anti-HCV ) , high levels of alanine transaminase ( ALT ) and alpha-fetoprotein ( AFP ) and a family history of HCC . Significantly increased risks of liver cirrhosis were associated with predictors of cirrhosis were increasing age , HbsAg , high levels of ALT and of AFP . Significant or borderline significant increases in risk of HCC death were associated with increasing age , male gender , HbsAg , high levels of AST and AFP . Adjusted for the significant variables , the mortality was lower by 41 % ( 95 % CI : -20 to 71 % , p = 0.1446 ) in the attenders compared to the non-attenders . The present study provides suggestive evidence on the efficacy of US screening in a selective high risk group in an endemic area of hepatitis B. A r and omized controlled trial would yield definitive evidence . Within the protocol of such a trial , a shorter interscreening interval for patients with liver cirrhosis is suggested BACKGROUND / AIMS An adequate preoperative disease staging is highly required before surgical treatment , even in gastrointestinal malignancies . Our study wants to give a contribution in order to define echolaparoscopy weight in gastrointestinal tumors and its impact in surgical therapy . METHODOLOGY 33 patients were affected by pancreas , 22 by stomach , 16 by extrahepatic biliary tract and 18 by liver cancers ; every patient was considered worthy of radical or palliative surgery according to preoperative staging ( thorax-abdominal CT and percutaneous ultrasonography ) . Paired sample t-tests were used to analyze the results of each method ical and probability values of less than 0.05 were considered significant . RESULTS Preoperative instrumental examinations gave correct evaluations only in 44 of 89 cases ( 49 % ) while echolaparoscopic gave correct evaluations in 82 on 89 cases ( 92 % ) ( P<0.05 ) . So after echolaparoscopic in only 7 cases we performed an explorative laparotomy . CONCLUSIONS Laparoscopy and ultrasound impact on therapy is worthy of attention . It seems to be able to give advantages in staging gastrointestinal malignancies , except for pancreas cancers , in which some limits and negative aspects have been demonstrated , regarding the possibility of giving correct diagnosis of portal axis infiltration Intraoperative ultrasonography ( IOUS ) is the most accurate diagnostic technique for staging hepatocellular carcinoma ( HCC ) , but has low accuracy in differentiating the new nodules detected in the cirrhotic liver . The aim of this preliminary report is to evaluate whether contrast-enhanced intraoperative ultrasonography ( CE-IOUS ) could provide additional information to IOUS in patients with HCC . From August 2002 to July 2003 , a prospect i ve validation cohort study was conducted . For this purpose , 16 consecutive patients underwent liver resection for HCC using IOUS and CE-IOUS . Intraoperatively , in all patients 4.8 mL of SonoVue was injected intravenously through a peripheral vein . IOUS depicted 16 new focal liver lesions : 10 with no enhancement peculiar to HCC at CE-IOUS pattern and at histology ( 4 ) or imaging follow-up ( 6 ) proved to be benign ; the remaining 6 had enhancement peculiar to HCC and histology confirmed this diagnosis . Two different patterns of enhancement were also recognized at CE-IOUS in those HCC nodules depicted preoperatively : one had no similarity to that observed at CT . CE-IOUS added findings to those of unenhanced IOUS in 50 % of patients . These results show that IOUS accuracy and specificity is improved by CE-IOUS , with a great impact on surgical strategy and oncological radicality . Furthermore , a wider experience with vascular enhancement patterns with CE-IOUS could provide a new classification for HCC nodules Hepatocellular carcinogenesis in cirrhosis is a multistage process that includes large regenerative nodules , dysplastic nodules , and hepatocarcinoma . The aim of this study was to establish whether contrast-enhanced Doppler ultrasonography ( US ) is able to distinguish between early hepatocellular carcinoma ( HCC ) and small nonmalignant nodules in cirrhosis . Between January 1998 and December 1999 , 500 cirrhotic patients with no previous history of HCC or evidence of hepatic focal lesions were enrolled and prospect ively followed-up with US every 6 months until December 2000 . Sixty-one patients developed focal lesions , 12 multifocal , and 49 monofocal . Biopsy of focal lesions , contrast-enhanced Doppler US , and spiral computed tomography ( CT ) were performed in 41 consecutive patients with small ( <3 cm ) monofocal lesions . Twenty nodules were diagnosed as HCC and 21 as nonmalignant ( 14 large regenerative nodules , 3 low- grade , and 4 high- grade dysplastic nodules ) by liver biopsy . Intratumoral arterial blood flow was detected in 19 of 20 ( 95 % ) HCC and 6 of 21 ( 28 % ) nonmalignant nodules by contrast-enhanced Doppler US ( P<.0001 ) . The mean peak resistance and pulsatility indices were 0.82 + /- 0.09 and 1.56 + /- 0.2 in HCC and 0.62 + /- 0.08 and 0.82 + /- 0.08 in dysplastic lesions ( P = .002 and .0001 ) , respectively . Spiral CT revealed arterial perfusion in 19 of 20 HCC and in 4 of 21 nonmalignant nodules ( high- grade dysplastic nodules ) . Four of the apparently false-positive nodules at enhanced Doppler US were high- grade dysplastic nodules and 2 evolved to HCC during follow-up . In conclusion , contrast-enhanced Doppler US is a noninvasive , very sensitive technique in differentiating malignant and premalignant lesions from nonmalignant focal lesions in the liver Background The accuracy of preoperative computed tomography ( CT ) scans in the era of modern imaging techniques with helical , high-resolution CT has not been adequately assessed . We review ed the data from our departmental prospect i ve data base with the hypothesis that intraoperative ultrasonography ( IOUS ) still detects more hepatic tumors than are evident on preoperative helical CT scans . Methods All patients who underwent surgical resection and /or radiofrequency ablation of primary or metastatic hepatic tumors between January 2001 and July 2002 were included in the review . All patients had preoperative helical CT imaging followed by hepatic IOUS . The number of malignant lesions and evidence of local disease identified by the preoperative CT scan versus IOUS and surgical exploration were compared . Results In this time period , 250 patients underwent surgical resection and /or radiofrequency ablation of hepatic tumors . In 67 ( 27 % ) of these patients , IOUS identified more hepatic tumors than were seen on preoperative helical CT scan . In eight patients ( 3 % ) , CT underestimated local extension of the disease into the diaphragm . The incidence of inaccurate preoperative prediction of the extent of disease increased significantly with a greater number of hepatic tumors . Conclusions IOUS identified additional hepatic tumors in 27 % of patients who underwent hepatic resection after state-of-the-art preoperative CT imaging . This study provides evidence that IOUS remains an essential part of the complete assessment of hepatic malignancies in patients who receive surgical treatment UNLABELLED The purpose of this study was to assess the accuracy of Cadence Contrast Pulse Sequencing ( Siemens-Acuson , CA ) method with injection of SonoVue ( Bracco Imaging SpA , Italy ) for the detection and characterisation of focal liver lesions in comparison with a reference modality during routine use . METHODS 138 consecutive patients ( 62 women , 76 men ; mean age : 52 years for women and 63 years for men ) corresponding to 144 examinations with 381 lesions participated in this prospect i ve study from December 2002 to November 2003 . Inclusion criteria were lesions detected by conventional US and the availability of a reference imaging examination ( CT or MR imaging ) within three weeks . The underlying liver lesions characterised by a reference modality ( including biopsy in 29 lesions ) were distributed as follows : haemangioma ( n = 56 ) , focal nodular hyperplasia ( n = 27 ) , hepatocellular carcinoma ( n = 44 ) , hepatocellular adenoma ( n = 5 ) , liver metastasis ( n = 174 ) , abscess ( n = 2 ) , cysts ( n = 45 ) , other benign lesions ( n = 24 ) and 3 peritoneal metastases . RESULTS A significant improvement was reported in the number of detected lesions between contrast-enhanced ultrasound and baseline ultrasonography ( 351 lesions versus 280 lesions , respectively , p < 0.01 ) , whereas no significant difference was noted between contrast-enhanced ultrasound and reference imaging ( 351 versus 377 lesions , respectively ) . On the whole , contrast-enhanced ultrasound allowed a complete diagnosis in 96 % of the detected nodules with a significant improvement compared to conventional sonography in which the diagnosis was suspected in only 52 % out of these cases ( p < 0.001 ) . No significant difference was noted between contrast-enhanced ultrasound and the reference modality concerning characterisation of nodules . CONCLUSION The present study clearly indicates that contrast-enhanced sonography using Sonovue and Cadence Contrast Pulse Sequencing allows real-time imaging with high accuracy and thus will be a competitive alternative to other modalities such as CT and MR imaging for liver imaging OBJECTIVE The objective of our study was to prospect ively evaluate the results of helical CT in the detection of hepatocellular carcinoma ( HCC ) in patients with cirrhosis undergoing orthotopic liver transplantation . SUBJECTS AND METHODS . Eighty-five patients with cirrhosis were studied preoperatively with biphasic helical CT . Arterial , portal , and equilibrium phase images were obtained after injection of 170 mL of contrast material at 5 mL/sec . The prospect i ve CT interpretation was compared with pathologic results on a lesion-by-lesion basis . RESULTS Pathologic examination found 85 cases of HCC in 51 patients . Helical CT enabled a correct diagnosis of HCC in 67 of 85 lesions for a sensitivity of 78.8 % . HCC nodules were hypervascular in the arterial phase and hypovascular in the equilibrium phase in 63.5 % ( 54/85 ) of patients . The false-negative rate was 21 % ( n = 18 ) , and the positive predictive value was 88 % . We had nine false-positive findings ( 11.8 % ) related to hemangiomas , transient hepatic attenuation differences , and regenerative nodules . Helical CT detected 61 % ( 23/38 ) of lesions smaller than 2 cm and 93.6 % ( 44/47 ) of lesions 2 cm or larger . CONCLUSION Helical CT is a useful preoperative imaging technique in cirrhotic patients who are c and i date s for orthotopic liver transplantation , although it is relatively insensitive for detection of small lesions ( < 2 cm ) The efficacy of contrast-enhanced magnetic resonance imaging ( MRI ) for detecting and characterizing , or excluding , hepatic masses was assessed in 404 patients , following the intravenous administration of mangafodipir trisodium ( MnDPDP ) injection , a hepatic MRI contrast agent . An initial contrast-enhanced computed tomography ( CT ) examination was followed by unenhanced MRI , injection of MnDPDP ( 5 micromol/kg IV ) , and enhanced MRI at 15 minutes post injection . Agreement of the radiologic diagnoses with the patients ' final diagnoses was higher for enhanced MRI and for the combined unenhanced and enhanced MRI evaluations than for unenhanced MRI alone or enhanced CT using the clinical diagnosis as the gold st and ard . Mangafodipir-enhanced MRI uniquely provided additional diagnostic information in 48 % of the patients , and patient management was consequently altered in 6 % of the patients . MnDPDP-enhanced MRI was comparable or superior to unenhanced MRI and enhanced CT for the detection , classification , and diagnosis of focal liver lesions in patients with known or suspected focal liver disease Abstract . The purpose of this study was to evaluate the diagnostic efficacy of iron-oxide-enhanced MRI vs CT during arterial portography ( CTAP ) and intraoperative ultrasound ( IOUS ) in detection of liver neoplasms . Seventeen patients with malignant focal liver lesions ( liver metastases , n=7 ) , hepatocellular carcinomas ( HCC , n=9 ) , and cholangiocellular carcinoma ( CCC , n=1 ) underwent presurgical Resovist-enhanced MRI and CTAP . Two independent observers ( A and B ) assessed the blinded images of unenhanced and iron-oxide-enhanced MRI vs CTAP for the presence , number , and location of the liver lesions . These results were compared lesion by lesion and segment by segment with the results of intraoperative ultrasound ( n=17 ) serving as the reference st and ard . Eighty lesions were detected by intraoperative ultrasound in 17 patients . In comparison with IOUS ( lesion-by-lesion analysis ) the sensitivity was 86.8 % for CTAP , 65 % for combined unenhanced MR imaging , and 86.8 % for combined Resovist-enhanced MRI as well as 86.8 % for the combination of unenhanced and Resovist-enhanced MRI . Compared with the sensitivity of combined unenhanced MRI the sensitivity of CTAP as well as the sensitivity of combined Resovist-enhanced MRI was significantly higher ( p<0.05 ) . False-positive results were much higher in CTAP as compared with combined unenhanced and SPIO-enhanced MRI . Using the segment-by-segment analysis the specificity of combined unenhanced MRI with 100 % ( 96.7–100 % ) as well as combined Resovist-enhanced MRI with 100 % ( 96.7–100 % ) was significantly higher ( p<0.05 ) in comparison with the specificity of CTAP with 91.1 % ( 83.2–96.1 % ) . The accuracy of combined unenhanced MRI was 100 % ( 93.2–100 % ) , combined Resovist-enhanced MRI 100 % ( 93.6–100 % ) and of CTAP 85.2 % ( 72.9–93.4 % ) . In the detection of focal liver lesions iron-oxide-enhanced MR imaging is superior to unenhanced MRI and similar to CTAP PURPOSE To evaluate the use of flash-echo contrast sonography ( FECS ) in subtraction mode in assessing small hepatocellular carcinoma ( HCC ) after percutaneous local ablation therapy . METHODS Between March 2000 and February 2002 , we prospect ively assessed small HCCs after percutaneous local ablation therapy using FECS in subtraction mode . Thirty-three patients ( 22 men , 11 women ) with 35 tumors ranging in size from 1.1 to 3.0 cm ( mean + /- SD , 2.0 + /- 0.5 ) were enrolled . Twenty-one tumors received percutaneous ethanol injection only , 13 tumors received percutaneous microwave ablation therapy only , and the remaining tumor received both treatments . CT , hepatic angiography , and follow-up were used as gold st and ards in analyzing the accuracy of FECS in detecting residual tumors . RESULTS The agreements between FECS and CT , FECS and hepatic angiography , and all 3 imaging modalities were 80 % ( 28/35 ) , 85.7 % ( 30/35 ) , and 77.1 % ( 27/35 ) , respectively . Twenty-one patients with 23 completely ablated tumors were followed up for 5 to 39 months ( mean + /- SD , 20.2 + /- 11.2 ) . Recurrent disease was detected in 11 ( 52.4 % ) patients ; local tumor recurrence occurred in 4 ( 17.4 % ) patients . The sensitivity , specificity , accuracy , and positive and negative predictive value of FECS in detecting viable tumors were 53.8 % ( 7/13 ) , 90.9 % ( 20/22 ) , 77.1 % ( 27/35 ) , 77.8 % ( 7/9 ) , and 76.9 % ( 20/26 ) , respectively . CONCLUSIONS FECS in subtraction mode shows good agreement with hepatic angiography and CT in the assessment of small HCC after percutaneous local ablation therapy . The sensitivity of FECS in detecting residual tumors is suboptimal BACKGROUND The objective of this study was to compare Levovist power Doppler ultrasound ( Levovist US ) with contrast-enhanced spiral computed tomography ( spiral CT ) , in the evaluation of the efficacy of percutaneous local ablation procedures , in patients with hepatocellular carcinoma ( HCC ) . MATERIAL S AND METHODS Forty-six patients with 62 HCC were studied using Levovist US and triphasic spiral CT , after treatment by radiofrequency ablation ( RFA ) ( 32 ) , percutaneous ethanol injection ( PEI ) ( 24 ) , transarterial chemoembolization ( TACE ) ( 4 ) , laser-therapy ( LT ) ( 1 ) and RFA plus TACE ( 1 ) . RESULTS Spiral CT scan showed contrast enhancement in 47 % of the cases ; at basal power Doppler ultrasound only 10 % of the nodules showed to be vascular but , after Levovist infusion , 72.5 % showed intralesional vascular spots . CONCLUSION We detected that residual tumor vascularity in HCC , after treatment using percutaneous local ablation procedures , was significantly increased by Levovist . Levovist US could be proposed as a good alternative in patients unfit for CT scanning due to allergies to io date contrast media , renal failure or cardiovascular disease and , moreover , could help to select those patients requiring a new treatment , without performing spiral CT , thereby reducing the cost of treatment and improving patient tolerance The purpose of this study was to compare dual-phase spiral computed tomography ( CT ) and magnetic resonance imaging ( MRI ) using dynamic gadolinium enhancement for liver lesion detection and characterization . Twenty-two consecutive patients underwent dual-phase spiral CT and MRI for the evaluation of focal liver disease within a 1-month period . Spiral CT and MR images were interpreted prospect ively , in a blinded fashion by separate , individual , experienced investigators , to determine lesion detection and characterization . Liver lesions were confirmed by surgery and pathology in 6 patients , and by clinical and imaging follow-up in the other 16 patients . Pathological correlation of a primary extrahepatic malignancy was available in 5 of the 16 patients who had metastatic liver disease . Spiral CT and MRI detected 53 and 63 lesions , and characterized 39 and 62 true positive lesions , respectively . A kappa statistic test was applied to assess agreement between MR and CT results . MR versus CT for lesion detection result ed in a kappa statistic of 0.54 ( 95 % confidence interval ) , indicating moderate agreement , and 0.32 ( 95 % confidence interval ) for lesion characterization , indicating only slight agreement . More lesions were detected on MR images than CT images in 6 ( 27 % ) patients , with lesions detected only on MR images in 4 ( 18 % ) patients . More lesions were characterized on MR images in 9 ( 41 % ) patients . In 9 patients with a discrepancy between MR and CT findings , the MR images added information considered significant to patient management in all 9 cases . MRI was moderately superior to dual-phase spiral CT for lesion detection , and was markedly superior for lesion characterization , with these differences having clinical significance PURPOSE To assess the utility of contrast-enhanced agent detection imaging ( ADI ) in the assessment of the therapeutic response to percutaneous radiofrequency ( RF ) ablation in patients with hepatocellular carcinoma ( HCC ) . MATERIAL S AND METHODS Ninety patients with a total of 97 nodular HCCs ( mean , 2.1+/-1.3 cm ; range , 1.0 - 5.0 cm ) treated with percutaneous RF ablation under the ultrasound guidance were evaluated with contrast-enhanced ADI after receiving an intravenous bolus injection of a microbubble contrast agent ( SH U 508A ) . We obtained serial contrast-enhanced ADI images during the time period from 15 to 90 s after the initiation of the bolus contrast injection . All of the patients underwent a follow-up four-phase helical CT at 1 month after RF ablation , which was then repeated at 2 - 4 month intervals during a period of at least 12 months . The results of the contrast-enhanced ADI were compared with those of the follow-up CT in terms of the presence or absence of residual unablated tumor and local tumor progression in the treated lesions . RESULTS On contrast-enhanced ADI , technical success was obtained in 94 ( 97 % ) of the 97 HCCs , while residual unablated tumors were found in three HCCs ( 3 % ) . Two of the three tumors that were suspicious ( was not proven ) for incomplete ablation were subjected to additional RF ablation . The remaining one enhancing lesion that was suspicious of a residual tumor on contrast-enhanced ADI was revealed to be reactive hyperemia at the 1-month follow-up CT . Therefore ; the diagnostic concordance between the contrast-enhanced ADI and 1-month follow-up CT was 99 % . Of the 94 ablated HCCs without residual tumors on both the contrast-enhanced ADI and 1-month follow-up CT after the initial RF ablation , five ( 5 % ) had CT findings of local tumor progression at a subsequent follow-up CT . CONCLUSION Despite its limitations in predicting local tumor progression in the treated tumors , contrast-enhanced ADI is potentially useful for evaluating the early therapeutic effect of percutaneous RF ablation for HCCs This was a prospect i ve study to evaluate tissue harmonic imaging ( THI ) for the diagnosis of focal liver lesions . A total of 15 review ers read 100 r and omly arranged liver images , a fundamental grey-scale image ( FGI ) and a THI ( transmitted : 2 MHz , received : 4 MHz ) of each of 50 patients ( 29 with liver cirrhosis , 42 with focal lesions ) taken from the same section . The mean value of overall accuracy for detecting lesions ( presence or absence ) was significantly higher with THI ( 82.3 % ) than with FGI ( 79.6 % ) ( t = 1 . 96 , p < 0.05 ) . When only the 29 cirrhosis patients were analyzed , the difference was more significant ( t = 2.48 , p < 0.02 ) . The correct count rate of the number of focal lesions was higher with THI ( 78 . 0 % ) than with FGI ( 67.0 % ) ( t = 3.61 , p < 0.005 ) in 23 cirrhosis patients with focal lesions . The correct diagnosis of HCC was achieved at a higher rate with THI ( 42.5 % ) than with FGI ( 36.8 % ) . THI was statistically effective for detecting focal lesions , particularly in cirrhotic livers AIM To prospect ively evaluate the usefulness of a pattern-based classification of contrast-enhanced sonographic findings for differential diagnosis of hepatic tumors . METHODS We evaluated the enhancement pattern of the contrast-enhanced sonography images in 586 patients with 586 hepatic lesions , consisting of 383 hepatocellular carcinomas , 89 metastases , and 114 hemangiomas . After injecting a galactose-palmitic acid contrast agent , lesions were scanned by contrast-enhanced harmonic gray-scale sonography in three phases : arterial , portal , and late . The enhancement patterns of the initial 303 lesions were classified retrospectively , and multiple logistic regression analysis was used to identify enhancement patterns that allowed differentiation between hepatic tumors . We then used the pattern-based classification of enhancement we had retrospectively devised to prospect ively diagnose 283 liver tumors . RESULTS Seven enhancement patterns were found to be significant predictors of different hepatic tumors . The presence of homogeneous or heterogeneous enhancement both in the arterial and portal phase was the typical enhancement pattern for hepatocellular carcinoma , while the presence of peritumoral vessels in the arterial phase and ring enhancement or a perfusion defect in the portal phase was the typical enhancement pattern for metastases , and the presence of peripheral nodular enhancement both in the arterial and portal phase was the typical enhancement pattern for hemangioma . The sensitivity , specificity , and accuracy of prospect i ve diagnosis based on the combinations of enhancement patterns , respectively , were 93.2 % , 96.2 % , and 94.0 % for hepatocellular carcinoma , 87.9 % , 99.6 % , and 98.2 % for metastasis , and 95.6 % , 94.1 % , and 94.3 % for hemangioma . CONCLUSION The pattern-based classification of the contrast-enhanced sonographic findings is useful for differentiating among hepatic tumors OBJECTIVE The purpose of this study was to compare the efficacy of contrast-enhanced pulse inversion harmonic imaging with contrast-enhanced power Doppler sonography and helical CT to determine incomplete local treatment after radiofrequency ablation in patients with hepatocellular carcinoma . MATERIAL S AND METHODS Thirty-five consecutive patients ( 24 men and 11 women ; mean age , 64 years ) with 43 hepatocellular carcinomas ( 3.6 + /- 1.1 cm ) were treated using internally cooled radiofrequency ablation therapy . Therapeutic response was evaluated at 4 months with dual-phase contrast-enhanced helical CT , conventional power Doppler Sonography , and pulse inversion harmonic imaging using a sonographic contrast agent ( SH-508 ) . CT and sonographic studies were review ed separately in r and om order by four radiologists at different consensus conferences . Sensitivity and specificity of the sonographic methods were determined using CT as a gold st and ard and results were compared using the McNemar test . RESULTS CT examinations identified residual tumor in 12 lesions ( 27.9 % ) . Although conventional contrast-enhanced power Doppler sonography identified residual viable tumor foci in four incompletely treated lesions ( 9.3 % ) , contrast-enhanced pulse inversion harmonic imaging identified residual tumoral enhancement in 10 lesions ( 23.3 % ) . Thus , the sensitivity of pulse inversion harmonic imaging ( 83.3 % ) was significantly greater ( p < 0.05 ) for detecting residual nonablated tumor compared with conventional contrast-enhanced power Doppler sonography . CONCLUSION Our study suggests that contrast-enhanced pulse inversion harmonic imaging may enable the detection of residual nonablated tumor in more cases than contrast-enhanced power Doppler sonography and may ultimately prove to be a useful adjunct for percutaneous ablation therapies . Nevertheless , contrast-enhanced axial imaging ( CT or MR imaging ) is currently the most sensitive test for managing thermal ablation for patients with hepatocellular carcinoma Kuwatsuru R , Kadoya M , Ohtomo K , et al. Comparison of gadobenate dimeglumine with gadopentetate dimeglumine for magnetic resonance imaging of liver tumors . Invest Radiol 2001;36:632–641 . rationale and objectives . To compare gadobenate dimeglumine ( Gd-BOPTA ) with gadopentetate dimeglumine ( Gd-DTPA ) for magnetic resonance imaging of the liver . methods .The contrast agent Gd-BOPTA or Gd-DTPA was administered at a dose of 0.1 mmol/kg to 257 patients suspected of having malignant liver tumors . Dynamic phase images , spin-echo images obtained within 10 minutes of injection , and delayed images obtained 40 to 120 minutes after injection were acquired . All postcontrast images were compared with unenhanced T1-weighted and T2-weighted images obtained immediately before injection . A full safety assessment was performed . results .The contrast efficacy for dynamic phase imaging was moderately or markedly improved in 90.9 % ( 110/121 ) and 87.9 % ( 109/124 ) of patients for Gd-BOPTA and Gd-DTPA , respectively . At 40 to 120 minutes after injection , the cor- responding improvements were 21.7 % ( 26/120 ) and 11.6 % ( 14/121 ) for spin-echo sequences and 44.5 % ( 53/119 ) and 19.0 % ( 23/121 ) for breath-hold gradient-echo sequences , respectively . The differences at 40 to 120 minutes after injection were statistically significant ( P < 0.02 ) . Increased information at 40 to 120 minutes after injection compared with information acquired within 10 minutes of injection was available for 24.0 % ( 29/121 ) of patients with Gd-BOPTA and for 14.5 % ( 18/124 ) of patients with Gd-DTPA ( P < 0.03 ) . Adverse events were seen in 4.7 % ( 6/128 ) and 1.6 % ( 2/127 ) of patients receiving Gd-BOPTA and Gd-DTPA , respectively . The difference was not statistically significant . conclusions .The efficacy of Gd-BOPTA is equivalent to that of Gd-DTPA for liver imaging during the dynamic phase and superior during the delayed ( 40–120 minutes ) phase of contrast enhancement . Both agents are safe for use in magnetic resonance imaging of the liver Objectives : This study was design ed to compare multidetector row computed tomography ( MDCT ) and CT-assisted hepatic arteriography (CTHA)/CT during arterial portography (CTAP)/angiography/contrast-enhanced CT ( CECT ) findings prospect ively for accuracy in the detection of liver metastasis and vascular involvement of the tumor . Methods : The study included 43 patients with pancreatic cancer who were evaluated from September 2002 to December 2003 . These patients underwent preoperative evaluation by angiography/CTHA/CTAP/CECT ( 7-mm thickness ) and by MDCT ( 1.25-mm thickness ) . Results : The sensitivity , specificity , positive predictive value , and negative predictive value of liver metastasis diagnosis were all superior using MDCT relative to CTHA/CTAP . The diagnostic accuracy of liver metastasis for patients with tumors less than 10 mm in diameter was particularly superior with MDCT relative to CTHA/CTAP . The surgical and pathological findings of vascular involvement were more accurately diagnosed by MDCT than by CTHA/CTAP/angiography/CECT . Although MDCT findings were generally similar to surgical findings of vascular involvement , MDCT overestimated the incidence of pathological vascular involvement . Conclusions : Multidetector row CT imaging can potentially offer more accurate staging of pancreatic cancer and may be useful to surgeons both in preoperative planning and for intraoperative guidance In the United States , cirrhotic patients with known or suspected hepatocellular carcinoma ( HCC ) are prioritized for liver transplantation . Noninvasive criteria for the diagnosis of HCC rely on arterial enhancement of a mass . The aim of this study was to determine whether clinical , laboratory , and / or radiologic data can improve the prediction of HCC in cirrhotic patients with an arterially-enhancing mass . Between May 2002 and June 2003 , dynamic gadolinium-enhanced magnetic resonance imaging ( MRI ) of consecutive patients with liver cirrhosis and a solid mass were review ed by 2 radiologists blinded to the clinical diagnosis . Clinical , laboratory , and radiologic data were recorded for all patients . A total of 94 patients with cirrhosis and an arterially-enhancing liver mass were studied , 66 ( 70 % ) of whom had HCC . Alpha-fetoprotein ( AFP ) > 20 ng/mL ( P = .029 ) , tumor size > 2 cm ( P = .0018 ) , and delayed hypointensity ( P = .0001 ) were independent predictors of HCC . Delayed hypointensity of an arterially-enhancing mass had a sensitivity of 89 % and a specificity of 96 % for HCC . The presence of delayed hypointensity was the only independent predictor of HCC among patients with arterially-enhancing lesions < 2 cm ( odds ratio , 6.3 ; 95 % confidence interval [ CI ] , 1.8 - 13 ) , with a sensitivity of 80 % and a specificity of 95 % . In conclusion , delayed hypointensity of an arterially-enhancing mass was the strongest independent predictor of HCC , regardless of the size of the lesion . If additional studies confirm our results , the noninvasive criteria utilized to make a diagnosis of HCC should be revised PURPOSE To compare the mangafodipir-enhanced magnetic resonance ( MR ) and superparamagnetic iron oxide (SPIO)-enhanced images for their ability to detect and characterize focal hepatic lesions . MATERIAL S AND METHODS Unenhanced , mangafodipir-enhanced , and SPIO-enhanced hepatic MR images obtained from 64 patients were analyzed . A total of 121 hepatic lesions were included : 66 hepatocellular carcinomas ( HCCs ) , 26 metastases , 14 hemangiomas , 5 cysts , 3 cholangiocarcinomas , 4 focal nodular hyperplasias ( FNHs ) , 2 abscesses , and 1 adenoma . Two radiologists independently review ed the two sets of images in a r and om order : 1 ) the unenhanced and mangafodipir-enhanced images ( the mangafodipir set ) and 2 ) the unenhanced and SPIO-enhanced images ( the SPIO set ) . This study compared the accuracy of lesion detection , the ability to distinguish between a benign and malignant lesion , and the ability to distinguish between the hepatocellular and nonhepatocellular origins of the lesions using the areas ( Az ) under the receiver operating characteristic ( ROC ) curve . RESULTS The overall accuracy for detecting focal lesions was significantly higher ( P < 0.05 ) with the SPIO set ( Az = 0.846 and 0.871 for readers 1 and 2 , respectively ) than with the mangafodipir set ( Az = 0.716 and 0.766 ) . Most of the lesions detected only with the SPIO-enhanced MR images by the readers were small HCCs . For lesions larger than 15 mm , the sensitivities of the two contrast enhancement techniques were similar for both readers . The accuracy of the mangafodipir and SPIO sets in distinguishing between benign and malignant lesions was comparable . The accuracy for distinguishing between the hepatocellular and nonhepatocellular origins of the lesions was significantly higher ( P < 0.05 ) using the mangafodipir set ( Az = 0.897 and 0.946 ) than using the SPIO set ( Az = 0.741 and 0.833 ) . CONCLUSION SPIO- and mangafodipir-enhanced images were comparable for detection of focal hepatic lesions other than small HCCs , which were better detected on the SPIO-enhanced images . Mangafodipir-enhanced images are likely better than the SPIO-enhanced images for distinguishing between focal liver lesions with a hepatocellular or nonhepatocellular origin BACKGROUND / AIMS This study was prospect ively conducted to eluci date the relationship between pre-/post-treatment power Doppler signals of hepatocellular carcinoma ( HCC ) and local recurrence . METHODS One hundred ninety-nine consecutive patients with 359 HCC lesions receiving percutaneous ethanol injection therapy ( PEIT ) as a first-line option were enrolled . Arterial power Doppler signals in the tumor were found in 130 nodules , but not detected in 229 . After confirmation of complete tumor necrosis on dynamic CT , Doppler signals in nodules were re-evaluated . Patients received periodical examinations to detect HCC recurrence . RESULTS Local HCC recurrence was observed in 36 lesions ; 22%(28/130 ) of the pretreatment signal positive lesions , in contrast to 3.5 % ( 8/229 ) of the pretreatment signal negative lesions ( P < 0.01 ) . Out of 130 signal positive nodules , signals disappeared in 120 ( 92 % ) after PEIT , but were present in ten ( 8 % ) . During the 25-month follow up , local recurrence was detected in 19 ( 16 % ) from the former , in contrast to nine ( 90 % ) from the latter ( P < 0.001 ) . Uni- and multivariate Cox analysis revealed that the presence of pre-/post-treatment power Doppler signals , histological differentiation and tumor number were independent factors for local recurrence . However , 3-year recurrence rate of new lesions was 51 % , but no predictors were identified . CONCLUSIONS Residual Doppler signals in tumor after PEIT were related to the local HCC recurrence OBJECTIVE Our purpose was to evaluate the value of contrast-enhanced coded phase-inversion harmonic imaging in showing the characteristic intranodular hemodynamics of hepatic tumors . SUBJECTS AND METHODS . Using a microbubble contrast agent we performed coded harmonic angio in 163 patients with 192 hepatic tumor nodules : 153 hepatocellular carcinomas , 13 metastases , 14 hemangiomas , eight dysplastic nodules , and four focal nodular hyperplasias . After injecting Levovist , we performed real-time scanning , interval-delay fast low-angle shot imaging , and sweep scanning in the early arterial phase , late vascular phase , and postvascular phase , respectively . RESULTS On contrast-enhanced coded harmonic angio , the typical hemodynamic pattern of hepatocellular carcinomas was shown as abundant tumor vessels supplied from the periphery to the center of the tumor and dense parenchymal tumor staining with fast washout ( sensitivity , 92.8 % ; specificity , 92.3 % ) . The characteristic hemodynamic pattern of metastases was peripheral tumor vessels with a rim parenchymal stain in the vascular phase followed by a perfusion defect in the postvascular phase ( sensitivity , 69.2 % ; specificity , 100 % ) . Hemangiomas were hypovascular in the early arterial phase with gradual spotty or cotton-wool pooling continuing to the late vascular phase ( sensitivity , 92.9 % ; specificity , 100 % ) . Dysplastic nodules were shown as having no early arterial supply with isovascularity in the late vascular phase ( sensitivity , 75 % ; specificity , 100 % ) . Focal nodular hyperplasias were shown to have a spoked wheel pattern of blood vessels accompanied by dense staining in interval-delay scanning ( sensitivity , 100 % ; specificity , 100 % ) . CONCLUSION Contrast-enhanced coded harmonic angio is a promising method to provide useful information for the differential diagnosis of hepatic tumors Purpose : To investigate prospect ively multidetector computed tomography ( CT ) ( MDCT ) and magnetic resonance ( MR ) imaging ( MRI ) in the preoperative assessment of focal liver lesions . Material and Methods : Multiphasic MDCT and conventional gadolinium‐enhanced MRI were performed on 31 consecutive patients prior to hepatic surgery . All images were blindly analyzed as consensus reading . Lesion counts and their relation to vascular structures and possible extrahepatic disease were determined . The data from the MDCT and MRI were compared with the results obtained by intraoperative ultrasound ( IOUS ) and palpation . Histopathologic verification was available . Results : At surgery , IOUS and palpation revealed 45 solid liver lesions . From these , preoperative MDCT detected 43 ( 96 % ) and MRI 35 ( 78 % ) deposits . MDCT performed statistically better than MRI in lesion detection ( P = 0.008 ) . Assessment of lesion vascular proximity was correctly determined by MDCT in 98 % of patients and by MRI in 87 % . Statistical difference was found ( P = 0.002 ) . IOUS and palpation changed the preoperative surgical plan as a result of extrahepatic disease in 8/31 ( 26 % ) cases . In MDCT as well in MRI extrahepatic involvement was suspected in two cases . Conclusion : MDCT was superior to MRI and nearly equal to IOUS in liver lesion detection and in the determination of lesion vascular proximity . However , both techniques fail to reliably detect extrahepatic disease OBJECTIVE The aim of this study was to compare tumor detectability by assessing the vascularity on power and color Doppler sonography and CT after transarterial embolization or percutaneous ethanol injection therapy or both in hepatocellular carcinoma . SUBJECTS AND METHODS Forty-seven nodules of hepatocellular carcinoma ( size , 28 + /- 7 mm [ mean + /- st and ard deviation ] ; range , 20 - 40 mm ) in 38 patients were treated with transarterial embolization ( n = 6 ) , percutaneous ethanol injection therapy ( n = 23 ) , and transarterial embolization plus percutaneous ethanol injection therapy ( n = 9 ) . Power Doppler sonography , color Doppler sonography , and CT were performed before and 2 weeks , 3 months , and 6 months after the treatments . The existence of hepatocellular carcinoma was confirmed by positive findings for color signals on both Doppler sonography techniques and for tumor stains on CT . All the tumors were determined to be malignant by microscopic examination of biopsy specimens . RESULTS Before the treatments , power Doppler sonography ( 100 % ) and CT ( 100 % ) were significantly more effective than color Doppler sonography ( 61.7 % ) ( p < 0.001 , for both ) . Six months after the treatments , the sensitivity of power Doppler sonography ( 87.5 % ) was significantly better than that of color Doppler sonography ( 12.5 % ) but was not significant in comparison with CT ( 66.6 % ) . However , power Doppler sonography detected color signals in two of three tumors in which iodized oil was accumulated and no tumor stain appeared on CT , and the two lesions detected with power Doppler sonography were carcinomas . CONCLUSION Power Doppler sonography can be considered the most sensitive technique in assessing the viability of hepatocellular carcinoma treated with transarterial embolization or percutaneous ethanol injection therapy or both PURPOSE To compare the sensitivity , positive predictive value , and diagnostic accuracy of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance ( MR ) imaging with those of 16-detector row computed tomography ( CT ) for the detection of hepatocellular carcinoma ( HCC ) in patients with hepatitis B-induced cirrhosis . MATERIAL S AND METHODS Institutional Review Board approval was obtained for this study , and informed consent was obtained from all patients . A total of 44 patients ( 36 men , eight women ; age range , 35 - 67 years ) with 59 HCCs and mild liver cirrhosis ( Child-Pugh score A or B ) underwent multiphasic CT and SPIO-enhanced MR imaging . The diagnosis of HCC was established at surgical resection ( n = 31 ) and percutaneous biopsy ( n = 28 ) . SPIO-enhanced MR imaging was composed of T2-weighted turbo spin-echo and T2 * -weighted gradient-echo sequences . Multiphasic CT consisted of four phases ( ie , early arterial , late arterial , portal venous , and equilibrium ) . Three observers independently analyzed each image in r and om order . Sensitivity , positive predictive value , and diagnostic accuracy were calculated by using the alternative free-response receiver operating characteristic analysis for multi-detector row CT and SPIO-enhanced MR imaging . RESULTS Although not significant ( P > .05 ) , the area under the receiver operating characteristic curve for SPIO-enhanced MR imaging ( mean , 0.90 ) was higher than that for multi-detector row CT ( mean , 0.82 ) for all observers . Also , although no significant difference was demonstrated by any of the three observers ( P > .05 ) , there was a trend toward increased sensitivity on both a per-lesion and a per-patient basis for SPIO-enhanced MR imaging ( mean , 84.7 % and 94.7 % , respectively ) compared with multi-detector row CT ( mean , 76.9 % and 88.6 % , respectively ) . No significant difference in positive predictive value was observed between modalities . CONCLUSION SPIO-enhanced MR imaging and multiphasic CT show similar diagnostic accuracy , sensitivity , and positive predictive value for the detection of HCC in patients with relatively mild hepatitis B-induced cirrhosis Detection and characterization of all focal lesions in the liver are critical for screening patients with chronic liver disease . The aim of this prospect i ve study was to investigate the accuracy of magnetic resonance imaging ( MRI ) and spiral computed tomography for the diagnosis of hepatic nodules in cirrhotic patients when compared with pathological findings of the explanted liver . From February 1997 to July 1999 , 34 cirrhotic patients waiting for orthotopic liver transplantation ( OLT ) ( mean age , 53.5 ± 9.3 years ; 24 males ) were included . All patients had MRI and spiral computed tomography examinations , and findings were matched with the histological findings . Data analyses were made using the McNemar chi-square test . Mean time between radiological examination ( MRI or spiral computed tomography ) and OLT was 43.8 ± 39 days . A total of 88 nodules were found in the 34 patients : 54 hepatocellular carcinoma ( HCC ) ( mean size , 18 ± 10 mm ) in 21 patients , 22 dysplastic nodules ( mean size , 10.7 ± 4.3 mm ) in 11 patients , and 12 macroregenerative nodules in 13 patients . Lesion-by-lesion analyses showed that sensitivity of MRI and spiral computed tomography for nodule , HCC or dysplastic nodule diagnosis was 44.3 and 31.8 % ( P = 0.02 ) , 61.1 and 51.9 % ( P = 0.2 ) , and 27.3 and 0 % ( P = 0.04 ) , respectively . Patient-by-patient analyses showed no statistical difference between spiral computed tomography and MRI for nodule diagnosis . In conclusion , in patients with liver cirrhosis , MRI is more accurate than spiral computed tomography for the detection of liver nodules and dysplastic nodules . However , tumour size is always a restricting factor for these two techniques , which are unable to detect small HCC in more than 60 % of cases |
13,533 | 28,064,527 | The major intervention pathway for ameliorating cognitive challenge seems to be placement out of the institutions which shows benefits and redresses some cognitive outcomes - yet not a total panacea .
The single study providing training and monitoring of harsh punishment and maltreatment showed immediate and decided reductions .
This data suggest , despite the paucity of studies , violence and abuse , by commission or omission is prevalent in institutions , has an effect on child well-being and is amenable to intervention .
Simple training or more complex structures to place children within conducive alternative environments ( or to avoid institutionalised placements in the first place ) seem to be the main pathway of intervention | Institutions are not necessarily good environments for children .
In the face of challenges such as HIV , Ebola , poverty , conflict and disaster the numbers have grown rather than reduced .
Some countries have closed institutions down -driven by findings that cognitive developmental delay is associated with institutional care .
Yet insight into abuse and violence within institutionalised setting s is neglected .
Maltreatment -violence and abuse -may be an issue .
This systematic review series addresses violence and abuse experiences in institutionalised care , exploring firstly the frequency of abuse/violence in institutions , secondly any interventions to reduce such violence or abuse and thirdly the perpetrators of such violence or abuse .
With a violence lens , cognitive delay may well be considered under the umbrella of neglect .
Maltreatment and abuse may be a driver of cognitive delay . | In a r and omized controlled trial , we compared ab and oned children reared in institutions to ab and oned children placed in institutions but then moved to foster care . Young children living in institutions were r and omly assigned to continued institutional care or to placement in foster care , and their cognitive development was tracked through 54 months of age . The cognitive outcome of children who remained in the institution was markedly below that of never-institutionalized children and children taken out of the institution and placed into foster care . The improved cognitive outcomes we observed at 42 and 54 months were most marked for the youngest children placed in foster care . These results point to the negative sequelae of early institutionalization , suggest a possible sensitive period in cognitive development , and underscore the advantages of family placements for young ab and oned children BACKGROUND We examined the effects of a foster care intervention on attention and emotion expression in socially deprived children in Romanian institutions . METHODS Institutionalized children were r and omized to enter foster care or to remain under institutional care . Subsequently , the institutionalized and foster care groups , along with a community-based comparison group , were evaluated on emotion tasks at 30 and 42 months of age . Behaviors reflecting positive and negative affect and attention were coded from videotapes . RESULTS Data indicated that at both age points , children who received the foster care intervention showed higher levels of attention and positive affect compared to children who remained institutionalized . Compared to the community sample , children in the foster care intervention showed higher levels of attention to the emotion-eliciting tasks at 42 months of age . CONCLUSIONS The results of this r and omized trial demonstrate the impact of a family-based intervention on the development of attention and positive affect This study examined classifications of attachment in 42-month-old Romanian children ( N = 169 ) . Institutionalized since birth , children were assessed comprehensively , r and omly assigned to care as usual ( CAU ) or to foster care , and compared to family-reared children . Attachment classifications for children in foster care were markedly different from those in the CAU . Importantly , children placed in foster care before 24 months were more likely to have secure attachments and if placed earlier were less likely to have disorganized or insecure-other attachments . Cognitive status predicted greater likelihood of organized attachment in the CAU and greater likelihood of secure attachment in the foster care and never-institutionalized groups . Foster care is an important intervention to reduce the adverse effects following early deprivation BACKGROUND Children reared in institutions experience elevated rates of psychiatric disorders . Inability to form a secure attachment relationship to a primary caregiver is posited to be a central mechanism in this association . We determined whether the ameliorative effect of a foster care ( FC ) intervention on internalizing disorders in previously institutionalized children was explained by the development of secure attachment among children placed in FC . Second we evaluated the role of lack of attachment in an institutionalized sample on the etiology of internalizing disorders within the context of a r and omized trial . METHODS A sample of 136 children ( aged 6 - 30 months ) residing in institutions was recruited in Bucharest , Romania . Children were r and omized to FC ( n = 68 ) or to care as usual ( CAU ; n = 68 ) . Foster parents were recruited , trained , and overseen by the investigative team . Attachment security at 42 months was assessed using the Strange Situation Procedure , and internalizing disorders at 54 months were assessed using the Preschool Age Psychiatric Assessment . RESULTS Girls in FC had fewer internalizing disorders than girls in CAU ( OR = 0.17 , p = .006 ) . The intervention had no effect on internalizing disorders in boys ( OR = 0.47 , p = .150 ) . At 42 months , girls in FC were more likely to have secure attachment than girls in CAU ( OR = 12.5 , p < .001 ) , but no difference was observed in boys ( OR = 2.0 , p = .205 ) . Greater attachment security predicted lower rates of internalizing disorders in both sexes . Development of attachment security fully mediated intervention effects on internalizing disorders in girls . CONCLUSION Placement into FC facilitated the development of secure attachment and prevented the onset of internalizing disorders in institutionalized girls . The differential effects of FC on attachment security in boys and girls explained gender differences in the intervention effects on psychopathology . Findings provide evidence for the critical role of disrupted attachment in the etiology of internalizing disorders in children exposed to institutionalization This study investigated the effects of early institutional care on memory and executive functioning . Subjects were participants in the Bucharest Early Intervention Project ( BEIP ) and included institutionalized children , children with a history of institutionalization who were assigned to a foster care intervention , and community children in Bucharest , Romania . Memory and executive functioning were assessed at the age of 8 years using the Cambridge Neuropsychological Test and Automated Battery ( CANTAB ) . As expected , children with a history of early institutional care performed worse on measures of both visual memory and executive functioning compared to their peers without a history of institutional care . In comparing children r and omly assigned to the foster care intervention with their peers who had continued care in the institution , initial comparisons did not show significant differences on any of the memory or executive functioning outcomes . However , for one of the measures of executive functioning , after controlling for birth weight , head circumference , and duration of time spent in early institutional care , the foster care intervention was a significant predictor of scores . These results support and extend previous findings of deficits in memory and executive functioning among school-age children with a history of early deprivation due to institutional care . This study has implication s for the millions of children who continue to experience the psychosocial deprivation associated with early institutional care 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 Contrary to some conventional wisdom , in this large study that r and omly sample d orphans and separated children from 5 countries , prevalence of reported traumatic events was no worse among those institutionalized than among those in family-based care . Reported incidence of physical or sexual abuse was actually higher for those in family-based care . Underst and ing the specific context , and elements contributing to potential harm and benefits in both family-based and institutional care , are essential to promoting the best interest of the child . Contrary to some conventional wisdom , in this large study that r and omly sample d orphans and separated children from 5 countries , prevalence of reported traumatic events was no worse among those institutionalized than among those in family-based care . Reported incidence of physical or sexual abuse was actually higher for those in family-based care . Underst and ing the specific context , and elements contributing to potential harm and benefits in both family-based and institutional care , are essential to promoting the best interest of the child . Background : Policy makers struggling to protect the 153 million orphaned and separated children ( OSC ) worldwide need evidence -based research on the burden of potentially traumatic events ( PTEs ) and the relative risk of PTEs across different types of care setting s. Methods : The Positive Outcomes for Orphans study used a 2-stage , cluster-r and omized sampling design to identify 1,357 institution-dwelling and 1,480 family-dwelling orphaned and separated children in 5 low- and middle-income countries ( LMICs ) in sub-Saharan Africa and Asia . We used the Life Events Checklist developed by the National Center for Posttraumatic Stress Disorder to examine self-reported PTEs among 2,235 OSC ages 10–13 at baseline . We estimated prevalence and incidence during 36-months of follow-up and compared the risk of PTEs across care setting s. Data collection began between May 2006 and February 2008 , depending on the site . Results : Lifetime prevalence by age 13 of any PTE , excluding loss of a parent , was 91.0 % ( 95 % confidence interval ( CI ) = 85.6 , 94.5 ) in institution-dwelling OSC and 92.4 % ( 95 % CI = 90.3 , 94.0 ) in family-dwelling OSC ; annual incidence of any PTE was lower in institution-dwelling ( 23.6 % [ 95 % CI = 19.4 , 28.7 ] ) than family-dwelling OSC ( 30.0 % [ 95 % CI = 28.1 , 32.2 ] ) . More than half of children in institutions ( 50.3 % [ 95 % CI = 42.5 , 58.0 ] ) and in family-based care ( 54.0 % [ 95 % CI = 50.2 , 57.7 ] ) had experienced physical or sexual abuse by age 13 . Annual incidence of physical or sexual abuse was lower in institution-dwelling ( 12.9 % [ 95 % CI = 9.6 , 17.3 ] ) than family-dwelling OSC ( 19.4 % [ 95 % CI = 17.7 , 21.3 ] ) , indicating statistically lower risk in institution-dwelling OSC ( risk difference = 6.5 % [ 95 % CI = 1.4 , 11.7 ] ) . Conclusion : Prevalence and incidence of PTEs were high among OSC , but contrary to common assumptions , OSC living in institutions did not report more PTEs or more abuse than OSC living with families . Current efforts to reduce the number of institution-dwelling OSC may not reduce incidence of PTEs in this vulnerable population . Protection of children from PTEs should be a primary consideration , regardless of the care setting OBJECTIVES To investigate the prevalence of stereotypies in children with a history of early institutional care , evaluate the efficacy of a foster care intervention compared with institutional care on the course of stereotypies , and describe correlates in language , cognition , and anxiety for children who exhibit stereotypies . DESIGN R and omized controlled trial . SETTING Institutions in Bucharest , Romania . PARTICIPANTS One hundred thirty-six children with a history of early institutional care . Intervention Comparison of a foster care intervention with continued care as usual in an institution . MAIN OUTCOME MEASURES The presence of stereotypies as well as outcomes in language , cognition , and anxiety . RESULTS At the baseline assessment prior to placement in foster care ( average age of 22 months ) , more than 60 % of children in institutional care exhibited stereotypies . Follow-up assessment s at 30 months , 42 months , and 54 months indicated that being placed in families significantly reduced stereotypies , and with earlier and longer placements , reductions became larger . For children in the foster care group , but not in the care as usual group , stereotypies were significantly associated with lower outcomes on measures of language and cognition . CONCLUSIONS Stereotypies are prevalent in children with a history of institutional care . A foster care intervention appears to have a beneficial/moderating role on reducing stereotypies , underscoring the need for early placement in home-based care for ab and oned children . Children who continue to exhibit stereotypies after foster care placement are significantly more impaired on outcomes of language and cognition than children without stereotypies and thus may be a target for further assessment s or interventions Look After the Child Investing in children has been demonstrated to improve their lives , both during the school-age years and afterward , as assessed by outcomes such as employment and income ; furthermore , these investments often help those in the most need . Campbell et al. ( p. 1478 ) report that these investments can also lead to improved adult health . Results from a r and omized and intensive intervention that involved 122 children in four cohorts recruited in the 1970s suggest that full-day child care for the first 5 years of life has produced adults in their 30s with better metabolic and cardiovascular health measures . Large investments in preschool children ’s education , health care , and nutrition provide long-term health benefits . High- quality early childhood programs have been shown to have substantial benefits in reducing crime , raising earnings , and promoting education . Much less is known about their benefits for adult health . We report on the long-term health effects of one of the oldest and most heavily cited early childhood interventions with long-term follow-up evaluated by the method of r and omization : the Carolina Abecedarian Project ( ABC ) . Using recently collected biomedical data , we find that disadvantaged children r and omly assigned to treatment have significantly lower prevalence of risk factors for cardiovascular and metabolic diseases in their mid-30s . The evidence is especially strong for males . The mean systolic blood pressure among the control males is 143 millimeters of mercury ( mm Hg ) , whereas it is only 126 mm Hg among the treated . One in four males in the control group is affected by metabolic syndrome , whereas none in the treatment group are affected . To reach these conclusions , we address several statistical challenges . We use exact permutation tests to account for small sample sizes and conduct a parallel bootstrap confidence interval analysis to confirm the permutation analysis . We adjust inference to account for the multiple hypotheses tested and for nonr and om attrition . Our evidence shows the potential of early life interventions for preventing disease and promoting health 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 We used structural MRI and EEG to examine brain structure and function in typically developing children in Romania ( n = 20 ) , children exposed to institutional rearing ( n = 29 ) , and children previously exposed to institutional rearing but then r and omized to a high- quality foster care intervention ( n = 25 ) . In so doing , we provide a unique evaluation of whether placement in an improved environment mitigates the effects of institutional rearing on neural structure , using data from the only existing r and omized controlled trial of foster care for institutionalized children . Children enrolled in the Bucharest Early Intervention Project underwent a T1-weighted MRI protocol . Children with histories of institutional rearing had significantly smaller cortical gray matter volume than never-institutionalized children . Cortical white matter was no different for children placed in foster care than never-institutionalized children but was significantly smaller for children not r and omized to foster care . We were also able to explain previously reported reductions in EEG α-power among institutionally reared children compared with children raised in families using these MRI data . As hypothesized , the association between institutionalization and EEG α-power was partially mediated by cortical white matter volume for children not r and omized to foster care . The increase in white matter among children r and omized to an improved rearing environment relative to children who remained in institutional care suggests the potential for developmental “ catch up ” in white matter growth , even following extreme environmental deprivation Background Leaders are struggling to care for the estimated 143,000,000 orphans and millions more ab and oned children worldwide . Global policy makers are advocating that institution-living orphans and ab and oned children ( OAC ) be moved as quickly as possible to a residential family setting and that institutional care be used as a last resort . This analysis tests the hypothesis that institutional care for OAC aged 6–12 is associated with worse health and wellbeing than community residential care using conservative two-tail tests . Methodology The Positive Outcomes for Orphans ( POFO ) study employed two-stage r and om sampling survey methodology in 6 sites across 5 countries to identify 1,357 institution-living and 1,480 community-living OAC ages 6–12 , 658 of whom were double-orphans or ab and oned by both biological parents . Survey analytic techniques were used to compare cognitive functioning , emotion , behavior , physical health , and growth . Linear mixed-effects models were used to estimate the proportion of variability in child outcomes attributable to the study site , care setting , and child levels and institutional versus community care setting s. Conservative analyses limited the community living children to double-orphans or ab and oned children . Principal Findings Health , emotional and cognitive functioning , and physical growth were no worse for institution-living than community-living OAC , and generally better than for community-living OAC cared for by persons other than a biological parent . Differences between study sites explained 2–23 % of the total variability in child outcomes , while differences between care setting s within sites explained 8–21 % . Differences among children within care setting s explained 64–87 % . After adjusting for sites , age , and gender , institution vs. community-living explained only 0.3–7 % of the variability in child outcomes . Conclusion This study does not support the hypothesis that institutional care is systematic ally associated with poorer wellbeing than community care for OAC aged 6–12 in those countries facing the greatest OAC burden . Much greater variability among children within care setting s was observed than among care setting s type . Method ologically rigorous studies must be conducted in those countries facing the new OAC epidemic in order to underst and which characteristics of care promote child wellbeing . Such characteristics may transcend the structural definitions of institutions or family homes Background . Approximately 153 million children worldwide are orphaned and vulnerable to potentially traumatic events ( PTEs ) . Gender differences in PTEs in low- and middle-income countries ( LMIC ) are not well-understood , although support services and prevention programs often primarily involve girls . Methods . The Positive Outcomes for Orphans study used a two-stage , cluster-r and omized sampling design to identify 2837 orphaned and separated children ( OSC ) in five LMIC in sub-Saharan Africa and Asia . We examined self-reported prevalence and incidence of several PTE types , including physical and sexual abuse , among 2235 children who were ≥10 years at baseline or follow-up , with a focus on gender comparisons . Results . Lifetime prevalence by age 13 of any PTE other than loss of a parent was similar in both boys [ 91.7 % ( 95 % confidence interval ( CI ) ( 85.0–95.5 ) ] and girls [ 90.3 % CI ( 84.2–94.1 ) ] in institutional-based care , and boys [ 92.0 % ( CI 89.0–94.2 ) ] and girls [ 92.9 % CI ( 89.8–95.1 ) ] in family-based care ; annual incidence was similarly comparable between institution dwelling boys [ 23.6 % CI ( 19.1,−29.3 ) ] and girls [ 23.6 % CI ( 18.6,−30.0 ) ] , as well as between family-dwelling boys [ 30.7 % CI ( 28.0,−33.6 ) ] and girls [ 29.3 % CI ( 26.8,−32.0 ) ] . Physical and sexual abuse had the highest overall annual incidence of any trauma type for institution-based OSC [ 12.9 % CI ( 9.6–17.4 ) ] and family-based OSC [ 19.4 % CI ( 14.5–26.1 ) ] , although estimates in each setting were no different between genders . Conclusion . Prevalence and annual incidence of PTEs were high among OSC in general , but gender-specific estimates were comparable . Although support services and prevention programs are essential for female OSC , programs for male OSC are equally important BACKGROUND Previous reports from the Bucharest Early Intervention Project suggested that children removed from institutions and placed into intervention displayed gains in IQ relative to children r and omized to remain in institutional care . METHOD The current report presents data from the 8-year follow-up of these children . One hundred and three of the original 136 children in the study were tested with the WISC IV . RESULTS Results reveal continued benefit from the intervention even though many of the children in both the intervention and control groups were no longer residing in their initial placements . Gains in IQ were particularly evident for those children who remained with their intervention family . There were also modest timing effects such that children placed earlier displayed higher scores on the WISC processing speed subscale . Early placement was also a significant predictor of a profile of stable , typical IQ scores over time . CONCLUSION These data suggest the continued importance of early intervention and the negative effects of severe psychosocial deprivation on the development of IQ scores across early childhood OBJECTIVES To determine effects of improved nurturing compared with institutional care on physical growth and to investigate the association between growth and cognitive development . DESIGN A r and omized controlled trial beginning in infants ( mean age , 21.0 months ; range , 5 - 32 months ) , with follow-up at 30 , 42 , and 54 months of age . SETTING Institutionalized and community children in Bucharest , Romania . PARTICIPANTS One hundred thirty-six healthy institutionalized children from 6 orphanages and 72 typically developing , never-institutionalized children . INTERVENTION Institutionalized children were r and omly assigned to receive foster care or institutional care as usual . OUTCOME MEASURES Auxology and measures of intelligence over time . RESULTS Growth in institutionalized children was compromised , particularly in infants weighing less than 2500 g at birth . Mean height and weight , though not head size , increased to near normal within 12 months in foster care . Significant independent predictors for greater catch-up in height and weight included age younger than 12 months at r and omization , lower baseline z scores , and higher caregiving quality , particularly caregiver sensitivity and positive regard . Baseline developmental quotient , birth weight , and height catch-up were significant independent predictors of cognitive abilities at follow-up . Each incremental increase of 1 in st and ardized height scores between baseline and 42 months was associated with a mean increase of 12.6 points ( SD , 4.7 points ) in verbal IQ ( P < .05 ) . CONCLUSIONS Foster care had a significant effect on growth , particularly with early placement and high- quality care . Growth and IQ in low-birth-weight children are particularly vulnerable to social deprivation . Catch-up growth in height under more nurturing conditions is a useful indicator of caregiving quality and cognitive improvement 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 Associations between early deprivation and memory functioning were examined in 9- to 11-year-old children . Children who had experienced prolonged institutional care prior to adoption were compared to children who were adopted early from foster care and children reared in birth families . Measures included the Paired Associates Learning task from the Cambridge Neuropsychological Test and Automated Battery ( CANTAB ) and a continuous recognition memory task during which ERPs were also recorded . Children who experienced prolonged institutionalization showed deficits in both behavioral memory measures as well as an attenuated P300 parietal memory effect . Results implicate memory function as one of the domains that may be negatively influenced by early deprivation in the form of institutional care OBJECTIVES To determine the effect of psychosocial deprivation early in life on motor development , assess the impact of a foster care intervention on improving motor development , and assess the association between motor and cognitive outcomes in children with a history of institutional care . STUDY DESIGN In a r and omized controlled trial , children living in Romanian institutions were r and omly assigned to care as usual in the institution or placed in family-centered foster care as part of the Bucharest Early Intervention Project . The average age at placement into foster care was 23 months . At age 8 years , the Bruininks-Oseretsky Test of Motor Proficiency , Second Edition , Short Form ( BOT2-SF ) was applied to assess the motor proficiency of children in both groups , as well as a never-institutionalized group from the Romanian community . RESULTS Children in the never-institutionalized group did significantly better on the BOT2-SF than children who had ever been institutionalized ( P < .001 ) . There was no significant difference in performance between children in the care as usual group and the foster care group . This finding also held true for all individual items on the BOT2-SF except sit-ups . Regression analyses revealed that the between-group and within-group differences in BOT2-SF scores were largely mediated by IQ . CONCLUSION Early deprivation had a negative effect on motor development that was not resolved by placement in foster care . This effect was predominantly mediated by IQ . This study highlights the importance of monitoring for and addressing motor delays in children with a history of institutionalization , particularly those children with low IQ OBJECTIVE There is increasing interest in the relations between adverse early experiences and subsequent psychiatric disorders . Institutional rearing is considered an adverse caregiving environment , but few studies have systematic ally examined its effects . This study aim ed to determine whether removing young children from institutional care and placing them with foster families would reduce psychiatric morbidity at 54 months of age . METHOD Young children living in institutions in Bucharest were enrolled when they were between 6 and 30 months of age . Following baseline assessment , 136 children were r and omly assigned to care as usual ( continued institutional care ) or to removal and placement in foster care that was created as part of the study . Psychiatric disorders , symptoms , and comorbidity were examined by structured psychiatric interviews of caregivers of 52 children receiving care as usual and 59 children in foster care when the children were 54 months of age . Both groups were compared to 59 typically developing , never-institutionalized Romanian children recruited from pediatric clinics in Bucharest . Foster care was created and supported by social workers in Bucharest who received regular consultation from U.S. clinicians . RESULTS Children with any history of institutional rearing had more psychiatric disorders than children without such a history ( 53.2 % versus 22.0 % ) . Children removed from institutions and placed in foster families were less likely to have internalizing disorders than children who continued with care as usual ( 22.0 % versus 44.2 % ) . Boys were more symptomatic than girls regardless of their caregiving environment and , unlike girls , had no reduction in total psychiatric symptoms following foster placement . CONCLUSIONS Institutional rearing was associated with substantial psychiatric morbidity . Removing young children from institutions and placing them in families significantly reduced internalizing disorders , although girls were significantly more responsive to this intervention than boys |
13,534 | 24,529,896 | No effect on OS was observed .
No PFS and OS benefit was detected with the other agents .
No improvement of OS was detected in patients treated with biological agents plus chemotherapy , while a significant PFS improvement was observed only for bevacizumab and cetuximab . | Metastatic triple-negative breast cancer ( mTNBC ) represents 15 % of invasive breast cancers .
Prognosis is poor , and there is no specific target therapy but biological agents combined with chemotherapy may be effective . | PURPOSE To investigate whether sunitinib plus docetaxel improves clinical outcomes for patients with human epidermal growth factor receptor 2 (HER2)/neu-negative advanced breast cancer ( ABC ) versus docetaxel alone . PATIENTS AND METHODS In this phase III study , patients were r and omly assigned to open-label combination therapy ( sunitinib 37.5 mg/d , days 2 to 15 every 3 weeks ; and docetaxel 75 mg/m(2 ) , day 1 every 3 weeks ) or monotherapy ( docetaxel 100 mg/m(2 ) every 3 weeks ) . Progression-free survival ( PFS ) was the primary end point . RESULTS Two hundred ninety-six patients were r and omly assigned to combination therapy , and 297 patients were assigned to monotherapy . Median PFS times were 8.6 and 8.3 months with combination therapy and monotherapy , respectively ( hazard ratio , 0.92 ; one-sided P = .265 ) . The objective response rate ( ORR ) was significantly higher with the combination ( 55 % ) than with monotherapy ( 42 % ; one-sided P = .001 ) . Duration of response was similar in both arms ( 7.5 months with the combination v 7.2 months with monotherapy ) . Median overall survival ( OS ) times were 24.8 and 25.5 months with combination therapy and monotherapy , respectively ( one-sided P = .904 ) . There were 107 deaths with the combination and 91 deaths with monotherapy . The frequency of common adverse events ( AEs ) was higher with the combination , as were treatment discontinuations caused by AEs . CONCLUSION The combination of sunitinib plus docetaxel improved ORR but did not prolong either PFS or OS compared with docetaxel alone when given to an unselected HER2/neu-negative cohort as first-line treatment for ABC . Sunitinib combination therapy may also have result ed in AEs that yield an unfavorable risk-benefit ratio . The sunitinib-docetaxel regimen evaluated in this study is not recommended for further use in ABC PURPOSE This r and omized , open-label phase II study compared the efficacy of sunitinib monotherapy with that of single-agent st and ard-of-care ( SOC ) chemotherapy in patients with previously treated advanced triple-negative breast cancer ( TNBC ) . METHODS Patients with advanced TNBC , relapsed after anthracycline- and taxane-based chemotherapy , were r and omized to receive either sunitinib ( 37.5 mg/day ) or the investigator 's choice of SOC therapy . Progression-free survival was the primary endpoint . RESULTS Median progression-free survival was 2.0 months with sunitinib and 2.7 months with SOC chemotherapy ( one-sided P = 0.888 ) . Median overall survival was not prolonged with sunitinib ( 9.4 months ) compared with SOC chemotherapy ( 10.5 months ; one-sided P = 0.839 ) . The objective response rate was 3 % with sunitinib and 7 % with SOC chemotherapy ( one-sided P = 0.962 ) . CONCLUSIONS Sunitinib monotherapy did not improve efficacy compared with SOC chemotherapy in patients with previously treated advanced TNBC , for which identification of effective treatments and therapeutic targets remains an urgent need . TRIAL REGISTRATION NCT00246571 PURPOSE This phase II study evaluated the efficacy and safety of ixabepilone as neoadjuvant therapy for invasive breast cancer not amenable to breast conservation surgery . Gene expression studies were undertaken using genes that were identified as potentially associated with sensitivity/resistance to ixabepilone in prior pre clinical investigations . PATIENTS AND METHODS Patients with invasive breast cancer > or= 3 cm were eligible . Ixabepilone 40 mg/m(2 ) was administered as a 3-hour intravenous infusion on day 1 of a 21-day cycle for four or fewer cycles . RESULTS One hundred sixty-one patients were treated . The overall complete pathologic response ( pCR ) rate was 18 % in breast and 29 % in estrogen receptor ( ER ) -negative patients . Gene expression data were available for 134 patients . ER gene expression ( ER1 ) was inversely related to pCR in breast and had a positive predictive value ( PPV ) of 37 % and negative predictive value ( NPV ) of 92 % . A 10-gene penalized logistic regression ( PLR ) model developed from 200 genes predictive of ixabepilone sensitivity in pre clinical experiments included ER and tau and had higher PPV ( 45 % ) and comparable NPV ( 89 % ) to ER1 . Grade 3 to 4 adverse events ( AEs ) were reported for 32 % of patients . Except for neutropenia and leukopenia , all grade 3 to 4 AEs occurred in < or= 3 % of patients . Reversible peripheral neuropathy was experienced by 3 % of patients . CONCLUSION ER , microtubule-associated protein tau , and a 10-gene PLR model that included ER were identified as predictors of ixabepilone-induced pCR . RESULTS indicate an inverse relation between ER expression levels and ixabepilone sensitivity . Neoadjuvant ixabepilone demonstrated promising activity and a manageable safety profile in patients with invasive breast tumors Gefitinib , an epidermal growth factor receptor tyrosine kinase inhibitor , has shown both anti-proliferative and anti-tumoral activity in breast cancer . This study was design ed to determine the effect of adding gefitinib to neoadjuvant epirubicin and cyclophosphamide ( EC ) on tumor response rates . Women with unilateral , primary operable , estrogen receptor negative invasive breast cancer ≥ 2 cm were eligible for inclusion . R and omized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib ( 250 mg daily ) or placebo . Primary endpoint was pathologic complete response ( pCR ) , and secondary endpoints were complete response ( CR ) and overall objective response ( OR ) . 181 patients were r and omized . A pCR was observed in 17 % ( 12/71 ) of patients treated with gefitinib and in 12 % ( 9/73 ) of patients treated with placebo ( 4.57 % difference , 95 % CI −7.19 to 6.33 ; P = 0.44 ) . CR was observed in 10 % of patients in both the gefitinib ( 7/71 ) and the placebo group ( 7/73 ) ( 0.27 % difference , 95 % CI −9.6 to 10.2 ; P = 0.96 ) . There was no significant difference in OR ( 5.96 % ; 95 % CI −9.9 to 21.9 ; P = 0.45 ) between the two groups . Post hoc subgroup analysis showed a significant difference in pCR between triple negative breast cancer ( TNBC ) and non-TNBC tumors ( P = 0.03 ) . More patients in the gefitinib arm had hematological toxicity ( P = 0.15 ) and discontinued treatment ( 9/94 vs. 2/86 ) because of adverse events ( AE ) . Tumor response rates were similar in the two groups . A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment . More patients in the gefitinib group discontinued treatment because of AE BACKGROUND We conducted a phase 3 , r and omized , double-blind , placebo-controlled trial of sorafenib , a multikinase inhibitor of tumor-cell proliferation and angiogenesis , in patients with advanced clear-cell renal-cell carcinoma . METHODS From November 2003 to March 2005 , we r and omly assigned 903 patients with renal-cell carcinoma that was resistant to st and ard therapy to receive either continuous treatment with oral sorafenib ( at a dose of 400 mg twice daily ) or placebo ; 451 patients received sorafenib and 452 received placebo . The primary end point was overall survival . A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo . Consequently , crossover was permitted from placebo to sorafenib , beginning in May 2005 . RESULTS At the January 2005 cutoff , the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( hazard ratio for disease progression in the sorafenib group , 0.44 ; 95 % confidence interval [ CI ] , 0.35 to 0.55 ; P<0.01 ) . The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death , as compared with placebo ( hazard ratio , 0.72 ; 95 % CI , 0.54 to 0.94 ; P=0.02 ) , although this benefit was not statistically significant according to the O'Brien-Fleming threshold . Partial responses were reported as the best response in 10 % of patients receiving sorafenib and in 2 % of those receiving placebo ( P<0.001 ) . Diarrhea , rash , fatigue , and h and -foot skin reactions were the most common adverse events associated with sorafenib . Hypertension and cardiac ischemia were rare serious adverse events that were more common in patients receiving sorafenib than in those receiving placebo . CONCLUSIONS As compared with placebo , treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed ; however , treatment is associated with increased toxic effects . ( Clinical Trials.gov number , NCT00073307 [ Clinical Trials.gov ] . ) BACKGROUND Whether progression-free survival ( PFS ) or overall survival ( OS ) is the more appropriate endpoint in clinical trials of metastatic cancer is controversial . In some disease and treatment setting s , an improvement in PFS does not result in an improved OS . METHODS We partitioned OS into two parts and expressed it as the sum of PFS and survival postprogression ( SPP ) . We simulated r and omized clinical trials with two arms that had respective medians for PFS of 6 and 9 months . We assumed no treatment difference in median SPP . We found the probability of a statistically significant benefit in OS for various median SPP and observed P values for PFS . We compared the sample sizes required for PFS vs OS for various median SPP . We compare our results with the literature regarding surrogacy of PFS for OS by use of the correlation between hazard ratios for PFS and OS . All statistical tests were two-sided . RESULTS For a trial with observed P value for improvement in PFS of .001 , there was a greater than 90 % probability for statistical significance in OS if median SPP was 2 months but less than 20 % if median SPP was 24 months . For a trial requiring 280 patients to detect a 3-month difference in PFS , 350 and 2440 patients , respectively , were required to have the same power for detecting a real difference in OS that is carried over from the 3-month benefit in PFS when the median SPP was 2 and 24 months . CONCLUSIONS Addressing SPP is important in underst and ing treatment effects . For clinical trials with a PFS benefit , lack of statistical significance in OS does not imply lack of improvement in OS , especially for diseases with long median SPP . Although there may be no treatment effect on SPP , its variability so dilutes the OS comparison that statistical significance is likely lost . OS is a reasonable primary endpoint when median SPP is short but is too high a bar when median SPP is long , such as longer than 12 months In February 2008 , the U.S. Food and Drug Administration ( FDA ) granted accelerated approval to bevacizumab ( Avastin ) in combination with paclitaxel as first-line treatment for HER-2 negative metastatic breast cancer . Approval was based on the results of E2100 , a cooperative-group r and omized trial that showed a 5.5-month increase in progression-free survival associated with the addition of bevacizumab to paclitaxel therapy.1,2 Confirmatory studies by Genentech , the manufacturer , however , showed that bevacizumab 's benefits for progression-free survival may be appreciably smaller than those shown in E2100 and have demonstrated convincingly that the addition of bevacizumab to the chemotherapy agents they have tested offers no . . |
13,535 | 31,682,676 | Conclusions and Relevance The findings suggest that MBTs are associated with moderate improvements in pain and small reductions in opioid dose and may be associated with therapeutic benefits for opioid-related problems , such as opioid craving and misuse . | Importance Mind-body therapies ( MBTs ) are emerging as potential tools for addressing the opioid crisis .
Knowing whether mind-body therapies may benefit patients treated with opioids for acute , procedural , and chronic pain conditions may be useful for prescribers , payers , policy makers , and patients .
Objective To evaluate the association of MBTs with pain and opioid dose reduction in a diverse adult population with clinical pain . | There have been cl aims that the postoperative course of patients may be improved by presentation during general anesthesia of therapeutic suggestions which predict a rapid and comfortable postoperative recovery . This study evaluated the effectiveness of such therapeutic suggestions under double-blind and r and omized conditions . A tape recording predicting a smooth recovery during a short postoperative stay without pain , nausea , or vomiting was played during anesthesia to about half the patients ( N = 109 ) , while the remaining , control patients were played a blank tape instead ( N = 100 ) . The patients were primarily undergoing operations on the fallopian tubes , total abdominal hysterectomy , vertical b and ing gastroplasty , cholecystectomy , and ovarian cystectomy or myomectomy . The anesthesia methods consisted of either isoflurane with 70 % nitrous oxide in oxygen to produce end-tidal concentrations of 1.0 , 1.3 , or 1.5 MAC ; or 70 % nitrous oxide in oxygen combined with high or low doses of opioids . Assessment s of the efficacy of the therapeutic suggestions in the recovery room and throughout the postoperative hospital stay included : the frequency of administration of analgesic and antiemetic drugs ; opioid doses ; the incidence of fever ; nausea , retching , and vomiting ; other gastrointestinal and urinary symptoms ; ratings of pain ; ratings of anxiety ; global ratings of the patients ' physical and psychological recoveries by the patients and their nurses ; and length of postoperative hospital stay . There were no meaningful , significant differences in postoperative recovery of patients receiving therapeutic suggestions and controls . These negative results were not likely to be due to insensitivity of the assessment s of recovery , as they showed meaningful interrelations among themselves and numerous differences in recovery following different types of surgery . Widespread utilization of therapeutic suggestions as a routine operating room procedure seems premature in the absence of adequate replication of previously published positive studies Immediately before they underwent femoral angiography , 45 patients were given one of three types of audiotapes : a relaxation response tape recorded for this study , a tape of contemporary instrumental music , or a blank tape . All patients were instructed to listen to their audiotape during the entire angiographic procedure . Each audiotape was played through earphones . Radiologists were not told the group assignment or tape contents . The patients given the audiotape with instructions to elicit the relaxation response ( n = 15 ) experienced significantly less anxiety ( P less than .05 ) and pain ( P less than .001 ) during the procedure , were observed by radiology nurses to exhibit significantly less pain ( P less than .001 ) and anxiety ( P less than .001 ) , and requested significantly less fentanyl citrate ( P less than .01 ) and diazepam ( P less than .01 ) than patients given either the music ( n = 14 ) or the blank ( n = 16 ) control audiotapes . Elicitation of the relaxation response is a simple , inexpensive , efficacious , and practical method to reduce pain , anxiety , and medication during femoral angiography and may be useful in other invasive procedures CONTEXT Previous studies on the effect of mindfulness-based stress reduction ( MBSR ) therapy on chronic pain syndromes have been hampered by study design . OBJECTIVE To evaluate short-term efficacy of MBSR therapy for improving quality of life in adults with failed back surgery syndrome ( FBSS ) . DESIGN A single-center , prospect i ve , r and omized , single-blind , parallel-group clinical trial . PATIENTS AND SETTING Participants were recruited from a multidisciplinary spine and rehabilitation center in the greater Portl and , Maine , area . INTERVENTIONS AND MAIN OUTCOME MEASURES Patients were r and omly assigned at baseline to receive either MBSR therapy plus traditional therapy or traditional therapy alone for an 8-week period . Those receiving MBSR therapy completed weekly group sessions , and the control group continued with their traditional care as prescribed by their medical care providers . At study enrollment and at 12-week follow-up , all participants completed question naires on pain , quality of life , functionality , analgesic use , and sleep quality . Patients in the intervention group also completed question naires at 40-week follow-up . RESULTS The final analysis included 25 patients with FBSS ; 15 patients were in the MBSR intervention arm , and 10 in the control group . At 12-week follow-up , patients in the intervention arm had a mean 7.0-point increase ( on an 108-point [ corrected ] scale ) in pain acceptance and quality of life on the Chronic Pain Assessment Question naire , a mean 3.6-point [ corrected ] decrease ( on a 24-point scale ) in functional limitation on the Rol and -Morris Disability Question naire , a mean 6.9-point [ corrected ] reduction ( on a 30-point scale ) in pain level on the Summary Visual Analog Scale for Pain , a mean 1.5-point [ corrected ] reduction ( on a 4-point scale ) in frequency of use and potency of analgesics used for pain and recorded on logs , and a mean 2.0-point [ corrected ] increase ( on a 5-point scale ) in sleep quality on the abridged Pittsburgh Sleep Quality Inventory . These results were statistically and clinical ly significant compared to outcomes for the control group . CONCLUSION The results suggest that MBSR can be a useful clinical intervention for patients with FBSS A prospect i ve study was design ed to compare two psychological support interventions in controlling peri-dressing change pain and anxiety in severely burned patients . Thirty patients with a total burned surface area of 10 - 25 % , requiring a hospital stay of at least 14 days , were r and omised to receive either hypnosis or stress reducing strategies ( SRS ) adjunctively to routine intramuscular pre-dressing change analgesia and anxiolytic drugs . Visual analogue scale ( VAS ) scores for anxiety , pain , pain control and satisfaction were recorded at 2-day intervals throughout the 14-day study period , before , during and after dressing changes . The psychological assistance was given on days 8 and 10 after hospital admission . The comparison of the two treatment groups indicated that VAS anxiety scores were significantly decreased before and during dressing changes when the hypnotic technique was used instead of SRS . No difference was observed for pain , pain control and satisfaction , although VAS scores were always better in the hypnosis group . The study also showed that , overall , psychological support interventions reduced pain and increased patient satisfaction . These results confirm the potential benefits of psychological assistance during dressing changes in burned patients Background Medical management of acute pain among hospital in patients may be enhanced by mind-body interventions . Objective We hypothesized that a single , scripted session of mindfulness training focused on acceptance of pain or hypnotic suggestion focused on changing pain sensations through imagery would significantly reduce acute pain intensity and unpleasantness compared to a psychoeducation pain coping control . We also hypothesized that mindfulness and suggestion would produce significant improvements in secondary outcomes including relaxation , pleasant body sensations , anxiety , and desire for opioids , compared to the control condition . Methods This three-arm , parallel-group r and omized controlled trial conducted at a university-based hospital examined the acute effects of 15-min psychosocial interventions ( mindfulness , hypnotic suggestion , psychoeducation ) on adult in patients reporting “ intolerable pain ” or “ inadequate pain control . ” Participants ( N = 244 ) were assigned to one of three intervention conditions : mindfulness ( n = 86 ) , suggestion ( n = 73 ) , or psychoeducation ( n = 85).Key Results Participants in the mind-body interventions reported significantly lower baseline-adjusted pain intensity post-intervention than those assigned to psychoeducation ( p < 0.001 , percentage pain reduction : mindfulness = 23 % , suggestion = 29 % , education = 9 % ) , and lower baseline-adjusted pain unpleasantness ( p < 0.001 ) . Intervention conditions differed significantly with regard to relaxation ( p < 0.001 ) , pleasurable body sensations ( p = 0.001 ) , and desire for opioids ( p = 0.015 ) , but all three interventions were associated with a significant reduction in anxiety ( p < 0.001 ) . Conclusions Brief , single-session mind-body interventions delivered by hospital social workers led to clinical ly significant improvements in pain and related outcomes , suggesting that such interventions may be useful adjuncts to medical pain management . Trial registration Trial Registry : Clinical Trials.gov ; registration ID number : NCT02590029URL : https:// clinical OBJECTIVE The purpose of this study was to determine whether hypnotic analgesia can reduce the need for intravenous sedation analgesia without increasing pain and anxiety levels during abortion . STUDY DESIGN A cohort of 350 women who were scheduled for surgical abortion ( < 14 weeks ' gestation ) were assigned r and omly to a st and ard care group or a group that received a st and ardized hypnotic analgesia intervention 20 minutes before and throughout the surgical procedure . Primary outcome was the difference between the 2 groups : ( 1 ) the proportion who received sedation ( yes/no ) during the surgical procedure and ( 2 ) self- assessment s of pain and anxiety during suction evacuation of uterus content . RESULTS Women who underwent hypnosis required less intravenous sedation analgesia ( 108/172 women ; 63 % ) than the control group ( 149/175 women ; 85 % ; P < .0001 ) and self-reported no difference in pain , but not in anxiety , levels during suction evacuation . CONCLUSION Hypnotic interventions can be effective as an adjunct to pharmacologic management of acute pain during abortion The effects of hypnosis/therapeutic suggestion in connection with intravenous sedation and surgery have been described in many clinical publications ; however , few r and omized , controlled , and blind studies have been performed in the outpatient area . The original study published in 2010 aim ed to evaluate the use of hypnosis/therapeutic suggestion as an adjunct to intravenous sedation in patients having third molar removal in an outpatient setting . The patients were r and omly assigned to a treatment or control group . The treatment group listened to a rapid conversational induction and therapeutic suggestions via headphones throughout the entire surgical procedure along with a st and ard sedation dose of intravenous anesthetic . The control group received intravenous anesthesia but listened to only music without any hypnotic intervention . The current replication study addressed several of the limitations of the original . Sample size was increased and selection of participants from a different geographic area in Pennsylvania . Intra-operative propofol administration , patient post-operative pain ratings , and post-operative prescription pain reliever consumption were all significantly reduced in the treatment compared to the control group . Implication s of these results are discussed Background Catastrophic thinking and fear-avoidance belief are negatively influencing severe acute pain following surgery causing delayed ambulation and discharge . We aim ed to examine if a preoperative intervention of cognitive-behavioural therapy ( CBT ) could influence the early postsurgical outcome following lumbar spinal fusion surgery ( LSF ) . Methods Ninety patients undergoing LSF due to degenerative spinal disorders were r and omly allocated to either the CBT group or the control group . Both groups received surgery and postoperative rehabilitation . In addition , the CBT group received a preoperative intervention focussed on pain coping using a CBT approach . Primary outcome was back pain during the first week ( 0–10 scale ) . Secondary outcomes were mobility , analgesic consumption , and length of hospitalisation . Data were retrieved using self-report question naires , assessment s made by physical therapists and from medical records . Results No difference between the groups ’ self-reported back pain ( p = 0.76 ) was detected . Independent mobility was reached by a significantly larger number of patients in the CBT group than the control group during the first three postoperative days . Analgesic consumption tended to be lower in the CBT group , whereas length of hospitalisation was unaffected by the CBT intervention . Conclusion Participation in a preoperative CBT intervention appeared to facilitate mobility in the acute postoperative phase , despite equally high levels of self-reported acute postsurgical pain in the two groups , and a slightly lower intake of rescue analgesics in the CBT group . This may reflect an overall improved ability to cope with pain following participation in the preoperative CBT intervention . Trial registration The study was approved by the Danish Protection Agency ( 2011 - 41 - 5899 ) and the Ethics Committee of the Central Denmark Region ( M-20110047 ) . The trial was registered in Current Controlled Trials ( IS RCT N42281022 ) BACKGROUND Breast cancer surgery is associated with side effects , including postsurgical pain , nausea , and fatigue . We carried out a r and omized clinical trial to test the hypotheses that a brief presurgery hypnosis intervention would decrease intraoperative anesthesia and analgesic use and side effects associated with breast cancer surgery and that it would be cost effective . METHODS We r and omly assigned 200 patients who were scheduled to undergo excisional breast biopsy or lumpectomy ( mean age 48.5 years ) to a 15-minute presurgery hypnosis session conducted by a psychologist or nondirective empathic listening ( attention control ) . Patients were not blinded to group assignment . Intraoperative anesthesia use ( i.e. , of the analgesics lidocaine and fentanyl and the sedatives propofol and midazolam ) was assessed . Patient-reported pain and other side effects as measured on a visual analog scale ( 0 - 100 ) were assessed at discharge , as was use of analgesics in the recovery room . Institutional costs and time in the operating room were assessed via chart review . RESULTS Patients in the hypnosis group required less propofol ( means = 64.01 versus 96.64 microg ; difference = 32.63 ; 95 % confidence interval [ CI ] = 3.95 to 61.30 ) and lidocaine ( means = 24.23 versus 31.09 mL ; difference = 6.86 ; 95 % CI = 3.05 to 10.68 ) than patients in the control group . Patients in the hypnosis group also reported less pain intensity ( means = 22.43 versus 47.83 ; difference = 25.40 ; 95 % CI = 17.56 to 33.25 ) , pain unpleasantness ( means = 21.19 versus 39.05 ; difference = 17.86 ; 95 % CI = 9.92 to 25.80 ) , nausea ( means = 6.57 versus 25.49 ; difference = 18.92 ; 95 % CI = 12.98 to 24.87 ) , fatigue ( means = 29.47 versus 54.20 ; difference = 24.73 ; 95 % CI = 16.64 to 32.83 ) , discomfort ( means = 23.01 versus 43.20 ; difference = 20.19 ; 95 % CI = 12.36 to 28.02 ) , and emotional upset ( means = 8.67 versus 33.46 ; difference = 24.79 ; 95 % CI = 18.56 to 31.03 ) . No statistically significant differences were seen in the use of fentanyl , midazolam , or recovery room analgesics . Institutional costs for surgical breast cancer procedures were $ 8561 per patient at Mount Sinai School of Medicine . Patients in the hypnosis group cost the institution $ 772.71 less per patient than those in the control group ( 95 % CI = 75.10 to 1469.89 ) , mainly due to reduced surgical time . CONCLUSIONS Hypnosis was superior to attention control regarding propofol and lidocaine use ; pain , nausea , fatigue , discomfort , and emotional upset at discharge ; and institutional cost . Overall , the present data support the use of hypnosis with breast cancer surgery patients The subjective experience of one 's environment is constructed by interactions among sensory , cognitive , and affective processes . For centuries , meditation has been thought to influence such processes by enabling a nonevaluative representation of sensory events . To better underst and how meditation influences the sensory experience , we used arterial spin labeling functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants . After 4 d of mindfulness meditation training , meditating in the presence of noxious stimulation significantly reduced pain unpleasantness by 57 % and pain intensity ratings by 40 % when compared to rest . A two-factor repeated- measures ANOVA was used to identify interactions between meditation and pain-related brain activation . Meditation reduced pain-related activation of the contralateral primary somatosensory cortex . Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions . Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula , areas involved in the cognitive regulation of nociceptive processing . Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation , an area implicated in reframing the context ual evaluation of sensory events . Moreover , reductions in pain unpleasantness also were associated with thalamic deactivation , which may reflect a limbic gating mechanism involved in modifying interactions between afferent input and executive-order brain areas . Together , these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information OBJECTIVE To assess benefits of mindfulness meditation and cognitive behavioral therapy (CBT)-based intervention for opioid-treated chronic low back pain ( CLBP ) . DESIGN 26-week parallel-arm pilot r and omized controlled trial ( Intervention and Usual Care versus Usual Care alone ) . SETTING Outpatient . SUBJECTS Adults with CLBP , prescribed ≥30 mg/day of morphine-equivalent dose ( MED ) for at least 3 months . METHODS The intervention comprised eight weekly group sessions ( meditation and CLBP-specific CBT components ) and 30 minutes/day , 6 days/week of at-home practice . Outcome measures were collected at baseline , 8 , and 26 weeks : primary -pain severity ( Brief Pain Inventory ) and function/disability ( Oswestry Disability Index ) ; secondary -pain acceptance , opioid dose , pain sensitivity to thermal stimuli , and serum pain-sensitive biomarkers ( Interferon-γ ; Tumor Necrosis Factor-α ; Interleukins 1ß and 6 ; C-reactive Protein ) . RESULTS Thirty-five ( 21 experimental , 14 control ) participants were enrolled and completed the study . They were 51.8 ± 9.7 years old , 80 % female , with severe CLBP-related disability ( 66.7 ± 11.4 ) , moderate pain severity ( 5.8 ± 1.4 ) , and taking 148.3 ± 129.2 mg/day of MED . Results of the intention-to-treat analysis showed that , compared with controls , the meditation-CBT group reduced pain severity ratings during the study ( P = 0.045 ) , with between-group difference in score change reaching 1 point at 26 weeks ( 95 % Confidence Interval : 0.2,1.9 ; Cohen 's d = 0.86 ) , and decreased pain sensitivity to thermal stimuli ( P < 0.05 ) , without adverse events . Exploratory analyses suggested a relationship between the extent of meditation practice and the magnitude of intervention benefits . CONCLUSIONS Meditation-CBT intervention reduced pain severity and sensitivity to experimental thermal pain stimuli in patients with opioid-treated CLBP Background Single-session hypnosis has never been evaluated as a premedication technique in patients undergoing coronary artery bypass grafting ( CABG ) . The aim of the present study was to evaluate the beneficial effects of clinical hypnotherapy on perioperative anxiety , pain perception , sedation , and necessity for ventilator assistance in patients undergoing CABG . Methods Double-blind , r and omized , clinical trial was performed . Forty-four patients undergoing CABG surgery were r and omized into two groups . The patients in group A received preprocedural hypnosis by an anesthesiologist . Patients in group B ( control ) had only information on the surgical intervention by the same anesthesiologist . State-Trait-Anxiety Index-I ( STAI-I ) and Beck Depression Inventory ( BDI ) were performed preoperatively in both groups . Visual analog scale ( VAS ) and Ramsay sedation scale ( RSS ) were evaluated on 0th , 1st , 2nd , 4th , 6th , 8th , 10th , 12th , and 24th hours , postoperatively . Postoperative anxiety level , analgesic drug consumption , and duration of ventilator assistance and intensive care unit ( ICU ) stay were also documented . Results When anxiety and depression levels were compared , significantly lower STA-I and BDI values were detected in group A after hypnotherapy ( p = 0.001 , p = 0.001 , respectively ) . Significantly less total doses of remifentanil ( 34.4 ± 11.4 vs. 50.0 ± 13.6 mg ) and morphine ( 4.9 ± 3.3 vs. 13.6 ± 2.7 mg ) were administered in group A in the postoperative period . Ventilator assistance duration ( 6.8 ± 2.0 vs. 8.9 ± 2.7 hours ) was also shorter in group A when compared with that in group B ( p = 0.007 ) . Conclusion Hypnosis session prior to surgery was an effective complementary method in decreasing presurgical anxiety , and it result ed in better pain control as well as reduced ventilator assistance following CABG surgery The aim of this r and omized controlled trial was to determine the effect of jaw relaxation , music and the combination of relaxation and music on postoperative pain after major abdominal surgery during ambulation and rest on postoperative days 1 and 2 . Opioid medication provided for pain , following abdominal surgery , does not always give sufficient relief and can cause undesired side effects . Thus , additional interventions such as music and relaxation may provide more complete relief . Previous studies have found mixed results due to small sample sizes and other method ological problems . In a rigorous experimental design , 500 subjects aged 18 - 70 in five Midwestern hospitals were r and omly assigned by minimization to a relaxation , music , relaxation plus music , or control group . Interventions were taught preoperatively and tested postoperatively . The same amount of time was spent with subjects in the control group . Pain was measured with the visual analogue sensation and distress of pain scales . Demographic and surgical variables , and milligrams of parenteral or oral opioids in effect at the time of testing were not significantly different between the groups , nor did they correlate with pain scores . Controlling for pretest sensation and distress , orthogonal a priori contrasts and multivariate analysis of covariance indicated that the three treatment groups had significantly less pain than the controls , ( P = 0.028 - 0.000 ) which was confirmed by the univariate analysis of covariance ( P = 0.018 - 0.000 ) . Post hoc multivariate analysis revealed that the combination group had significantly less sensation and distress of pain than the control group on all post-tests ( P = 0.035 - 0.000 ) , and the relaxation and music groups had significantly less on all tests ( P = 0.022 - 0.000 ) except after ambulation . At post ambulation those using relaxation did not have significantly less pain than the controls on both days and those using music did not on day 1 , although there were some univariate effects . A corresponding significant decrease in mastery of the interventions from pre to post ambulation suggests the need for reminders to focus on the intervention during this increased activity . Physicians and nurses preparing patients for surgery and caring for them afterward , should encourage patients to use relaxation and music as adjuvants to medication for postoperative pain & NA ; Few controlled clinical trials of psychological interventions for cancer pain relief exist in spite of frequent support for their importance as adjuncts to medical treatment . This study compared oral mucositis pain levels in 4 groups of cancer patients receiving bone marrow transplants ( BMT ) : ( 1 ) treatment as usual control , ( 2 ) therapist support , ( 3 ) relaxation and imagery training , and ( 4 ) training in a package of cognitive‐behavioral coping skills which included relaxation and imagery . A total of 94 patients completed the study which involved two training sessions prior to treatment and twice a week ‘ booster ’ sessions during the first 5 weeks of treatment . Results confirmed our hypothesis that patients who received either relaxation and imagery alone or patients who received the package of cognitive‐behavioral coping skills would report less pain than patients in the other 2 groups . The hypothesis that the cognitive‐behavioral skills package would have an additive effect beyond relaxation and imagery alone was not confirmed . Average visual analogue scale ( VAS ) report of pain within the therapist support group was not significantly lower than the control group ( P = 0.103 ) nor significantly higher than the training groups . Patient reports of relative helpfulness of the interventions for managing pain and nausea matched the results of VAS reports . From these results , we conclude that relaxation and imagery training reduces cancer treatment‐related pain ; adding cognitive‐behavioral skills to the relaxation with imagery does not , on average , further improve pain relief & NA ; Chronic pain patients who show aberrant drug‐related behavior often are discontinued from treatment when they are noncompliant with their use of opioids for pain . The purpose of this study was to conduct a r and omized trial in patients who were prescribed opioids for noncancer back pain and who showed risk potential for or demonstration of opioid misuse to see if close monitoring and cognitive behavioral substance misuse counseling could increase overall compliance with opioids . Forty‐two patients meeting criteria for high‐risk for opioid misuse were r and omized to either st and ard control ( High‐Risk Control ; N = 21 ) or experimental compliance treatment consisting of monthly urine screens , compliance checklists , and individual and group motivational counseling ( High‐Risk Experimental ; N = 21 ) . Twenty patients who met criteria indicating low potential for misuse were recruited to a low‐risk control group ( Low‐Risk Control ) . Patients were followed for 6 months and completed pre‐ and post‐ study question naires and monthly electronic diaries . Outcomes consisted of the percent with a positive Drug Misuse Index ( DMI ) , which was a composite score of self‐reported drug misuse ( Prescription Drug Use Question naire ) , physician‐reported abuse behavior ( Addiction Behavior Checklist ) , and abnormal urine toxicology results . Significant differences were found between groups with 73.7 % of the High‐Risk Control patients demonstrating positive scores on the DMI compared with 26.3 % from the High‐Risk Experimental group and 25.0 % from the Low‐Risk Controls ( p < 0.05 ) . The results of this study demonstrate support for the benefits of a brief behavioral intervention in the management of opioid compliance among chronic back pain patient at high‐risk for prescription opioid misuse UNLABELLED This paper examines whether a telephone-based , automated maintenance enhancement program can help to reduce opioid and nonsteroidal anti-inflamatory drugs ( NSAID ) analgesic use in patients with chronic pain . Following 11 weeks of group cognitive-behavioral therapy ( CBT ) , 51 subjects with chronic musculoskeletal pain were r and omized to 1 of 2 study groups . Twenty-six subjects participated in 4 months of a Therapeutic Interactive Voice Response ( TIVR ) program in addition to st and ard follow-up care , while a control group of 25 subjects received st and ard follow-up care only . TIVR is an automated , telephone-based tool developed for the maintenance and enhancement of CBT skills . Opioid analgesic use decreased in the experimental group in both follow-ups : 4 and 8 months postCBT . In addition , at 8-month follow-up , 21 % of the TIVR subjects had discontinued the use of opioid analgesics , 23 % had discontinued NSAIDS , and 10 % had discontinued antidepressant medications . In contrast , the control group showed increases in opioid and NSAIDS use . Analysis of covariance ( ANCOVA ) revealed significant between-group differences in opioid analgesic use at 8-month follow up ( P = .004 ) . We have previously demonstrated the efficacy of TIVR to decrease pain and improve coping ; this analysis demonstrates that the use of TIVR may also result in concurrent reductions in opioid analgesic and NSAID medications use . PERSPECTIVE This article demonstrates that the Therapeutic Interactive Voice Response maintenance enhancement program can help to reduce opioid analgesic use in patients with chronic pain . This automated maintenance enhancement program could potentially assist patients not only to decrease pain and improve coping , but also to diminish the likelihood of opioid dependence Burn patients must often endure intense pain during their regular dressing changes . The aim of the present study was to investigate the therapeutic effect of rapid induction analgesia ( RIA ) on resting and procedural pain , anticipatory anxiety , relaxation levels and medication consumption in 30 hospitalized burn patients . Patients rated levels of pain and relaxation for four burn care sessions . RIA was conducted twice on 15 patients , whereas dressing changes proceeded as usual in 15 control patients . When asked to recall pain during the dressing changes , patients remembered an experience which was worse in its entirety than the average of spot ratings taken during the burn care procedure . However , self-reported ratings of the sensory and affective components of pain decreased significantly during and after RIA , particularly in patients who became readily absorbed , and relaxation increased during burn care . Anticipatory anxiety decreased before dressing changes in the RIA group , and analgesic intake decreased between treatment sessions . The promising outcome of this study confirms RIA as a viable adjunct to narcotic treatment for pain control during burn care AIM To assess whether psychological intervention reduces postembolization pain during hepatic arterial chemoembolization therapy . METHODS Two hundred and sixty-two patients , who required hepatic arterial chemoembolization for hepatic malignancy and postembolization pain , were r and omized into control group ( n = 46 , receiving medication ) and intervention group ( n = 216 , receiving psychological intervention and medication in turn ) . The symptom checklist-90 ( SCL-90 ) was used to scale the psychological symptoms of the patients before operation . Pain was scored with a 0 to 10 numeric rating scale ( NRS-10 ) before and after analgesia as well as after psychological intervention ( only in intervention group ) . RESULTS All psychological symptomatic scores measured with SCL-90 in the intervention group were higher than the normal range in Chinese ( P < 0.05 ) . The somatization , phobia and anxiety symptomatic scores were associated with pain numerical rating score before analgesia ( r = 0.141 , 0.157 and 0.192 , respectively , P < 0.05 ) . Patients in both groups experienced pain relief after medication , psychotherapy or psychotherapy combined with medication during the procedure ( P < 0.01 ) . Only some patients in the intervention group reported partial or entire pain relief ( 29.17 % and 2.31 % ) after psychological intervention . The pain score after analgesia in the intervention group was significantly lower than that in the control group ( P < 0.01 ) . CONCLUSION Severe psychological distress occurs in patients with hepatic malignancy . Psychological intervention reduces pain scores significantly during hepatic arterial chemoembolization therapy and is thus , highly recommended as a complementary approach to drug analgesia Abstract The effects of hypnosis/therapeutic suggestion in connection with intravenous sedation and surgery have been described in many clinical publications ; however , few r and omized , controlled , and blind studies have been performed in the outpatient area . This study aim ed to evaluate the use of hypnosis/therapeutic suggestion as an adjunct to intravenous ( IV ) sedation in patients having 3rd molar removal in an outpatient setting . The patients were r and omly assigned to a treatment ( n = 46 ) or control ( n = 54 ) group . The treatment group listened to a rapid conversational induction and therapeutic suggestions via headphones throughout the entire surgical procedure along with a st and ard sedation dose of intravenous anesthetic . The control group listened to only music without any hypnotic intervention . Intraoperative Propofol administration , patient postoperative pain ratings , and postoperative prescription pain reliever consumption were all significantly reduced in the treatment compared to the control group . Implication s of these results are discussed BACKGROUND : The management of postoperative pain in elderly orthopaedic patients is critical for advancing patient outcomes and improving the use of healthcare re sources . Adequate pain control without adverse side effects , such as confusion and sedation , is crucial to promote comfort and participation in rehabilitation therapies among all patients but particularly among elderly joint replacement patients . Without adequate pain control , physical therapy is delayed and the risk of complications increases . One area of investigation that holds promise for improved treatment outcomes involves the use of complementary therapies , such as guided imagery . PURPOSE : The purpose of this pilot study was to test the effects of a guided imagery intervention in the older adult patient who has undergone joint replacement surgery . SAMPLE AND METHODS : This pilot study used a two-group experimental repeated measures design . A sample of 13 patients , age 55 years and older , were recruited . The control group received usual care and a music audio tape . The experimental group received usual care and a guided imagery audio tape intervention . FINDINGS AND DISCUSSION : Trends in this pilot study demonstrated positive outcomes for pain relief , decreased anxiety , and decreased length of stay . Complementary therapy holds the promise of increasing positive outcomes . Further research is needed to vali date these findings with a larger postoperative sample and in other population s as well . CLINICAL IMPLICATION S : There is a critical need to incorporate the use of guided imagery and other complementary therapies into all nursing curricula . Nurses must develop expertise and be ready and able to act as patient educators and advocates in the use of these interventions in programs of care and institutional policy BACKGROUND Unrelieved pain after surgery can lead to complications , prolonged hospital stay , and delayed recovery . Because of side effects from opioids and differences in response , it is important to use non-pharmacological methods in addition to analgesics to decrease patient discomfort and anxiety . AIMS We examined the effects of a systematic method of relaxing the body on the sensory and affective components of postoperative pain , anxiety , and opioid intake after initial ambulation . DESIGN A r and omized controlled trial with relaxation and control groups was used . METHOD The convenience sample of 102 adults underwent abdominal surgery at a large hospital in Thail and . Systematic relaxation was used for 15 minutes during recovery from the first ambulation after surgery . Pain was measured with 100 mm Visual Analogue Sensation and Distress of Pain Scales before and after the intervention . State anxiety was measured before surgery and after the intervention ; opioid intake was recorded 6 hours later . RESULTS The relaxation group had less post-test sensation and distress of pain ( 26 and 25 mm less , respectively ) than the control group ( P = 0.001 ) . Relaxation did not result in significantly less anxiety or 6-hour opioid intake . However , group differences in state anxiety were in the expected direction and fewer participants in the relaxation group requested opioids . Nearly all reported that systematic relaxation reduced their pain and increased their sense of control . CONCLUSION Substantial reductions in the sensation and distress of pain were found when postoperative patients used systematic relaxation . Although tested in Thail and , we recommend that nurses in other countries try systematic relaxation with postoperative patients , in addition to analgesic medication , measuring pain scores and asking about cultural acceptance CONTEXT Postoperative management of pain after total joint arthroplasty remains a challenge despite advancements in analgesics . Evidence shows that complementary modalities with mind-body and tactile-based approaches are valid and effective adjuncts to reduce pain and anxiety postoperatively . OBJECTIVE To investigate the effectiveness of the " M " Technique ( M ) , a registered method of structured touch using a set sequence and number of strokes , and a consistent level of pressure on h and s and feet , compared with guided imagery and usual care , for the reduction of pain and anxiety in patients undergoing elective total knee or hip replacement surgery . METHODS R and omized controlled trial : M-TIJRP ( MiTechnique and guided Imagery in Joint Replacement Patients [ Mighty Junior P ] ) . At a community hospital , 225 male and female patients , aged 38 to 90 years , undergoing elective total hip or knee replacement were r and omly assigned to 1 of 3 groups ( 75 patients in each ) : M , guided imagery , or usual care . They were blinded to their assignment until the intervention . MAIN OUTCOME MEASURES Reduction of pain and anxiety postoperatively . Secondary outcomes measured use of pain medication and patient satisfaction . RESULTS This study yielded positive findings for the management of pain and anxiety in patients undergoing elective joint replacement using M and guided imagery for 18 to 20 minutes compared with usual care . M showed the largest predicted decreases in both pain and anxiety between groups . There was no significant difference in narcotic pain medication use between groups . Patient satisfaction survey ratings were highest for M , followed by guided imagery . CONCLUSION The benefit of M may be because of the specifically structured sequence of touch by competent caring , trained providers Background : Most postoperative patients have unrelieved pain despite the use of patient-controlled analgesia . Nurses need additional effective modalities . Relaxation and music ( RM ) , in addition to analgesics , have been shown to reduce pain more than do analgesics alone . Objectives : The objectives of the study were to test an intervention of patient teaching for pain management ( PT ) and compare it with RM for immediate and general effects on postoperative pain . Methods : Patients having abdominal surgery and receiving patient-controlled analgesia aged 18 - 75 years ( n = 517 ) were r and omized to four groups : PT , RM , a combination ( PTRM ) , and a control . A 2 × 2 factorial design was used to assess PT-Effects and RM-Effects . Immediate effects on pain were measured on visual analogue sensation and distress scales before and after five 20-min tests in the first 2 days . Because participants also listened independently , general nonimmediate effects were examined at eight other times . Results : Using multivariate analysis of covariance with contrasts and pretest control , immediate RM-Effects on pain were found at Day 1 a.m. ( p < .001 ) , Day 1 p.m. ( p = .04 ) , and Day 2 a.m. ( p = .04 ) . No PT-Effects or nonimmediate RM-Effects were found . Discussion : Patient teaching did not result in less pain and did not support the theoretical proposition that PT reduces pain . However , the immediate RM-Effects supported the proposition that nonpharmacological adjuvants to analgesics can ease pain without adding side effects Irritable bowel syndrome ( IBS ) is a prevalent functional disorder characterized by abdominal pain and hypervigilance to gastrointestinal sensations . We hypothesized that mindfulness training ( MT ) , which promotes nonreactive awareness of emotional and sensory experience , may target underlying mechanisms of IBS including affective pain processing and catastrophic appraisal s of gastrointestinal sensations . Seventy five female IBS patients were r and omly assigned to participate in either 8 weeks of MT or a social support group . A theoretically grounded , multivariate path model tested therapeutic mediators of the effect of MT on IBS severity and quality of life . Results suggest that MT exerts significant therapeutic effects on IBS symptoms by promoting nonreactivity to gut-focused anxiety and catastrophic appraisal s of the significance of abdominal sensations coupled with a refocusing of attention onto interoceptive data with less emotional interference . Hence , MT appears to target and ameliorate the underlying pathogenic mechanisms of IBS Purpose : This study was design ed to determine whether music or music in combination with therapeutic suggestions in the intra‐operative period under general anaesthesia could improve the recovery of hysterectomy patients Inadequate pain control in older patients who have undergone abdominal surgery can lead to many complications . This study investigates the effect of systematic relaxation techniques on pain and anxiety in older patients undergoing abdominal surgery . One hundred twenty-four patients were r and omly assigned into the experimental and control groups . The systematic relaxation techniques consisted of older patients in the experimental group slowly reading relaxing sentences during recovery in ambulation after the surgery . Patients ' satisfaction with pain and anxiety relief was recorded , as was their use of opioid analgesia . Statistically significant differences in pain and anxiety , and in analgesic use , were reported between the patients in experimental and control groups after the intervention . These relaxation techniques can be incorporated into the care plan to reduce pain and anxiety after surgery as well as offering a measure for increasing the patients ' independence in pain management control BACKGROUND Non-pharmacological behavioural adjuncts have been suggested as efficient safe means in reducing discomfort and adverse effects during medical procedures . We tested this assumption for patients undergoing percutaneous vascular and renal procedures in a prospect i ve , r and omised , single-centre study . METHODS 241 patients were r and omised to receive intraoperatively st and ard care ( n=79 ) , structured attention ( n=80 ) , or self-hypnotic relaxation ( n=82 ) . All had access to patient-controlled intravenous analgesia with fentanyl and midazolam . Patients rated their pain and anxiety on 0 - 10 scales before , every 15 min during and after the procedures . FINDINGS Pain increased linearly with procedure time in the st and ard group ( slope 0.09 in pain score/15 min , p<0.0001 ) , and the attention group ( slope 0.04/15 min ; p=0.0425 ) , but remained flat in the hypnosis group . Anxiety decreased over time in all three groups with slopes of -0.04 ( st and ard ) , -0.07 ( attention ) , and -0.11 ( hypnosis ) . Drug use in the st and ard group ( 1.9 units ) was significantly higher than in the attention and hypnosis groups ( 0.8 and 0.9 units , respectively ) . One hypnosis patient became haemodynamically unstable compared with ten attention patients ( p=0.0041 ) , and 12 st and ard patients ( p=0.0009 ) . Procedure times were significantly shorter in the hypnosis group ( 61 min ) than in the st and ard group ( 78 min , p=0.0016 ) with procedure duration of the attention group in between ( 67 min ) . INTERPRETATION Structured attention and self-hypnotic relaxation proved beneficial during invasive medical procedures . Hypnosis had more pronounced effects on pain and anxiety reduction , and is superior , in that it also improves haemodynamic stability The purpose of this investigation was to evaluate the effects of guided imagery on postoperative outcomes in patients undergoing same-day surgical procedures . Forty-four adults scheduled for head and neck procedures were r and omly assigned into 2 groups for this single-blind investigation . Anxiety and baseline pain levels were documented preoperatively . Both groups received 28 minutes of privacy , during which subjects in the experimental group listened to a guided imagery compact disk ( CD ) , but control group patients received no intervention . Data were collected on pain and narcotic consumption at 1- and 2-hour postoperative intervals . In addition , discharge times from the postoperative anesthesia care unit ( PACU ) and the ambulatory procedure unit and patient satisfaction scores were collected . The change in anxiety levels decreased significantly in the guided imagery group ( P = .002 ) . At 2 hours , the guided imagery group reported significantly less pain ( P = .041 ) . In addition , length of stay in PACU in the guided imagery group was an average of 9 minutes less than in the control group ( P = .055 ) . The use of guided imagery in the ambulatory surgery setting can significantly reduce preoperative anxiety , which can result in less postoperative pain and earlier PACU discharge times Abstract Little attention has been paid to the effectiveness of hypnosis in improving the results of surgery in Iran . One hundred and twenty patients scheduled for laparoscopic cholecystectomy were r and omly divided into either control ( st and ard care ) or experimental ( hypnosis ) groups . Prior to surgery and again after surgery , abdominal pain , nausea , and vomiting were assessed . The results suggest that hypnosis could effectively reduce pain after laparoscopic cholecystectomy and significantly reduce hospitalization time Thirty-two patients hospitalized for the care of major burns were r and omly assigned to groups that received hypnosis , lorazepam , hypnosis with lorazepam , or placebo controls as adjuncts to opioids for the control of pain during dressing changes . Analysis of scores on the Visual Analogue Scale indicated that although pain during dressing changes decreased over consecutive days , assignment to the various treatment groups did not have a differential effect . This finding was in contrast to those of earlier studies and is likely attributable to the low baseline pain scores of subjects who participated . A larger number of subjects with low baseline pain ratings will likely be necessary to replicate earlier findings . The results are argued to support the analgesic advantages of early , aggressive opioid use via PCA or through careful staff monitoring and titration of pain drugs High levels of pain , significant anxiety , or depressive symptoms before surgery put patients at elevated risk for chronic pain and prolonged opioid use following surgery . The purpose of this preliminary study was to assess the efficacy of a 1-day Acceptance and Commitment Therapy ( ACT ) workshop in " at-risk " veterans for the prevention of chronic pain and opioid use following orthopedic surgery . In a r and omized controlled trial , 88 at-risk veterans undergoing orthopedic surgery were assigned to treatment as usual ( TAU ; n = 44 ) or TAU plus a 1-day ACT workshop ( n = 44 ) . Pain levels and opioid use were assessed up to 3 months following surgery . Pain acceptance and values-based behavior were assessed at baseline and 3-month follow-up . Participants who completed the ACT workshop reached pain and opioid cessation sooner than those in TAU . Postoperative complications exhibited a moderating effect on these outcomes , such that the effects of ACT were greater in patients without complications . Increases in pain acceptance and values-based behavior , processes targeted in ACT , were related to better outcomes . These promising results merit further investigation in a larger clinical trial . Providing an intervention before surgery for at-risk veterans has the potential to change clinical practice from a focus on management of postoperative pain to prevention of chronic pain in at-risk individuals . PERSPECTIVE This pilot study compared the effects of a 1-day preventive behavioral intervention ( ACT ) to TAU in at-risk veterans undergoing orthopedic surgery . Three months following the intervention , veterans receiving ACT exhibited quicker cessation of pain and opioid use . Focusing on preoperative pain management may help prevent chronic postsurgical pain Elective surgery patients were prepared for surgery with training in muscle relaxation or with information about sensations they would experience . Relaxation reduced hospital stay , pain , and medication for pain and increased strength , energy , and postoperative epinephrine levels . Information reduced hospital stay . Personality variables ( denial , fear , aggressiveness ) were associated with recovery and influenced patients ' responses to preparation . Less frightened patients benefited more from relaxation than did very frightened patients . Nonaggressive patients reacted to information with decreased hospital stay along with increased pain , medication , and epinephrine . Aggressive patients responded to information with decreased hospital stay along with decreased pain , medication , and epinephrine . Patients using denial were not harmed by preparation . A catharsis/moderation model is proposed to explain how information benefits patients . An active coping model is proposed to explain the benefits of relaxation . This study suggests that behavioral preparation benefits even frightened , aggressive , or denying elective surgical patients PURPOSE To determine how hypnosis and empathic attention during percutaneous tumor treatments affect pain , anxiety , drug use , and adverse events . MATERIAL S AND METHODS For their tumor embolization or radiofrequency ablation , 201 patients were r and omized to receive st and ard care , empathic attention with defined behaviors displayed by an additional provider , or self-hypnotic relaxation including the defined empathic attention behaviors . All had local anesthesia and access to intravenous medication . Main outcome measures were pain and anxiety assessed every 15 minutes by patient self-report , medication use ( with 50 mug fentanyl or 1 mg midazolam counted as one unit ) , and adverse events , defined as occurrences requiring extra medical attention , including systolic blood pressure fluctuations ( > or = 50 mm Hg change to > 180 mm Hg or < 105 mm Hg ) , vasovagal episodes , cardiac events , and respiratory impairment . RESULTS Patients treated with hypnosis experienced significantly less pain and anxiety than those in the st and ard care and empathy groups at several time intervals and received significantly fewer median drug units ( mean , 2.0 ; interquartile range [ IQR ] , 1 - 4 ) than patients in the st and ard ( mean , 3.0 ; IQR , 1.5 - 5.0 ; P = .0147 ) and empathy groups ( mean , 3.50 ; IQR , 2.0 - 5.9 ; P = .0026 ) . Thirty-one of 65 patients ( 48 % ) in the empathy group had adverse events , which was significantly more than in the hypnosis group ( eight of 66 ; 12 % ; P = .0001 ) and st and ard care group ( 18 of 70 ; 26 % ; P = .0118 ) . CONCLUSIONS Procedural hypnosis including empathic attention reduces pain , anxiety , and medication use . Conversely , empathic approaches without hypnosis that provide an external focus of attention and do not enhance patients ' self-coping can result in more adverse events . These findings should have major implication s in the education of procedural personnel & NA ; Few controlled clinical trials have tested the efficacy of psychological techniques for reducing cancer pain or post‐chemotherapy nausea and emesis . In this study , 67 bone marrow transplant patients with hematological malignancies were r and omly assigned to one of four groups prior to beginning transplantation conditioning : hypnosis training (HYP);cognitive behavioral coping skills training (CB);therapist contact control ( TC ) ; ortreatment as usual ( TAU ; no treatment control ) . Patients completed measures of physical functioning ( Sickness Impact Profile ; SIP ) and psychological functioning ( Brief Symptom Inventory ; BSI ) , which were used as covariates in the analyses . Biodemographic variables included gender , age and a risk variable based on diagnosis and number of remissions or relapses . Patients in the HYP , CB and TC groups met with a clinical psychologist for two pre‐transplant training sessions and ten in‐hospital “ booster ” sessions during the course of transplantation . Forty‐five patients completed the study and provided all covariate data , and 80 % of the time series outcome data . Analyses of the principal study variables indicated that hypnosis was effective in reducing reported oral pain for patients undergoing marrow transplantation . Risk , SIP , and BSI pre‐transplant were found to be effective predictors of inpatient physical symptoms . Nausea , emesis and opioid use did not differ significantly between the treatment groups . The cognitive behavioral intervention , as applied in this study , was not effective in reducing the symptoms measured This study was design ed to confirm the effect of therapeutic intraoperative auditory suggestion on recovery from anesthesia , to establish the effect of preoperative suggestion , and to assess implicit memory for intraoperative information using an indirect memory task . Sixty consenting unpremedicated patients scheduled for elective gynecologic surgery were r and omly divided into three equal groups : Group 1 received a tape of therapeutic suggestions preoperatively , and the story of Robinson Crusoe intraoperatively ; Group 2 heard the story of Peter Pan preoperatively and therapeutic suggestions intraoperatively ; Group 3 heard the Crusoe story preoperatively and the Peter Pan story intraoperatively . A st and ardized anesthetic technique was used with fentanyl , propofol , isoflurane , and nitrous oxide . After surgery , all patients received patientcontrolled analgesia ( PCA ) with a st and ardized regimen . In the 24 h postsurgery , morphine use was recorded every 6 h and at 24 h an indirect memory test ( free association ) was used to test for memory of the stories . Anxiety scores were measured before surgery and at 6 and 24 h postsurgery . There were no significant differences between groups for postoperative morphine use , pain or nausea scores , anxiety scores , or days spent in hospital after surgery . Seven of 20 patients who heard the Pan story intraoperatively gave a positive association with the word " Hook , " whereas 2 of 20 who did not hear the story gave such an association . Indirect memory for the Pan story was established using confidence interval ( CI ) analysis . ( The 95 % CI for difference in proportion did not include zero ) . No indirect memory for the Crusoe story could be demonstrated . This study did not confirm previous work which suggested that positive therapeutic auditory suggestions , played intraoperatively , reduced PCA morphine requirements . In contrast , a positive implicit memory effect was found for a story presented intraoperatively . ( Anesth Analg 1996;82:148 - 52 The clinical utility of hypnosis for controlling pain during burn wound debridement was investigated . Thirty hospitalized burn patients and their nurses su bmi tted visual analog scales ( VAS ) for pain during 2 consecutive daily wound debridements . On the 1st day , patients and nurses su bmi tted baseline VAS ratings . Before the next day 's would debridement , Ss received hypnosis , attention and information , or no treatment . Only hypnotized Ss reported significant pain reductions relative to pretreatment baseline . This result was corroborated by nurse VAS ratings . Findings indicate that hypnosis is a viable adjunct treatment for burn pain . Theoretical and practical implication s and future research directions are discussed The present study explored the effect of positive intrasurgical suggestion during the anesthetic state on postsurgical pain . One-half of the patients who were undergoing elective cholecystectomy or hysterectomy received strong positive intrasurgical suggestion directed specifically towards reducing pain . The control patients received information about pain without suggestion content . There was no effect on postsurgical pain measured by the McGill Pain Question naire and a visual analogue scale . The lack of effect on postsurgical pain indicates that intrasurgical suggestion does not provide a therapeutic method to achieve pain control Twenty patients undergoing cardiac surgery were seen one or more times by a psychiatrist who performed two functions . In a supportive fashion he cleared up any misconceptions the patient had about the forthcoming surgery and he taught him a simple autohypnotic technique . Twenty controls , matched for relevant variables , received routine preoperative care . Contrary to the report of others , a single visit by the psychiatrist did not influence the incidence of postoperative delirium , anxiety , depression , pain , or medication requirements . However , there was a trend for patients receiving a greater number of preoperative visits to have a lower incidence of detected delirium . Age was the only factor in this study that differed significantly between delirious and nondelirious patients OBJECTIVE Opioid pharmacotherapy is now the leading treatment for chronic pain , a problem that affects nearly one third of the U.S. population . Given the dramatic rise in prescription opioid misuse and opioid-related mortality , novel behavioral interventions are needed . The purpose of this study was to conduct an early-stage r and omized controlled trial of Mindfulness-Oriented Recovery Enhancement ( MORE ) , a multimodal intervention design ed to simultaneously target mechanisms underpinning chronic pain and opioid misuse . METHOD Chronic pain patients ( N = 115 ; mean age = 48 ± 14 years ; 68 % female ) were r and omized to 8 weeks of MORE or a support group ( SG ) . Outcomes were measured at pre- and posttreatment , and at 3-month follow-up . The Brief Pain Inventory was used to assess changes in pain severity and interference . Changes in opioid use disorder status were measured by the Current Opioid Misuse Measure . Desire for opioids , stress , nonreactivity , reinterpretation of pain sensations , and re appraisal were also evaluated . RESULTS MORE participants reported significantly greater reductions in pain severity ( p = .038 ) and interference ( p = .003 ) than SG participants , which were maintained by 3-month follow-up and mediated by increased nonreactivity and reinterpretation of pain sensations . Compared with SG participants , participants in MORE evidence d significantly less stress arousal ( p = .034 ) and desire for opioids ( p = .027 ) , and were significantly more likely to no longer meet criteria for opioid use disorder immediately following treatment ( p = .05 ) ; however , these effects were not sustained at follow-up . CONCLUSIONS Findings demonstrate preliminary feasibility and efficacy of MORE as a treatment for co-occurring prescription opioid misuse and chronic pain . ( PsycINFO Data base Record ( c ) 2014 APA , all rights reserved ) BACKGROUND Pain arising in burns sufferers is often severe and protracted . The prospect of a dressing change can heighten existing pain by impacting both physically and psychologically . In this trial we examined whether pre-procedural virtual reality guided relaxation added to patient controlled analgesia with morphine reduced pain severity during awake dressings changes in burns patients . METHODS We conducted a prospect i ve r and omized clinical trial in all patients with burns necessitating admission to a tertiary burns referral centre . Eligible patients requiring awake dressings changes were r and omly allocated to single use virtual reality relaxation plus intravenous morphine patient controlled analgesia ( PCA ) infusion or to intravenous morphine patient controlled analgesia infusion alone . Patients rated their worst pain intensity during the dressing change using a visual analogue scale . The primary outcome measure was presence of 30 % or greater difference in pain intensity ratings between the groups in estimation of worst pain during the dressing change . FINDINGS Of 88 eligible and consenting patients having awake dressings changes , 43 were assigned to virtual reality relaxation plus intravenous morphine PCA infusion and 43 to morphine PCA infusion alone . The group receiving virtual reality relaxation plus morphine PCA infusion reported significantly higher pain intensities during the dressing change ( mean=7.3 ) compared with patients receiving morphine PCA alone ( mean=5.3 ) ( p=0.003 ) ( 95 % CI 0.6 - 2.8 ) . INTERPRETATION The addition of virtual reality guided relaxation to morphine PCA infusion in burns patients result ed in a significant increase in pain experienced during awake dressings changes . In the absence of a vali date d predictor for responsiveness to virtual reality relaxation such a therapy can not be recommended for general use in burns patients having awake dressings changes A single-blind , r and omized prospect i ve trial was performed at a university hospital to determine if preoperative relaxation training will decrease pain and narcotic dem and postoperatively . A convenience sample of 49 patients undergoing lumbar and cervical spine surgery was r and omized to receive instruction on relaxation techniques or routine preoperative information before surgery . Pain score and narcotic dem and in the first 48 hours after surgery were the primary outcomes . Pain scores were higher in the relaxation ( 4.8 ± 1.7 ) versus the st and ard preparation group ( 3.9 ± 1.7 ) on postoperative day one ( POD ) 1 , but lower on POD 2 ( 3.9 ± 1.9 vs 4.1 ± 1.9 ) , whereas narcotic use ( milligrams of IV morphine per hour ) was higher in the relaxation group on POD 1 ( 1.14 ± 0.94 vs 0.54 ± 0.55 ) and POD 2 ( 0.86 ± 0.73 vs 0.50 ± 0.61 ) . The differences were significant for narcotic dem and ( P = 0.01 ) but not for pain ( P = 0.94 ) . In conclusion , our results could not support the use of relaxation training for reducing postoperative pain and narcotic dem and in this selected surgical population The effects of hypnosis in connection with surgery have been described in many clinical publications , but few controlled studies have been published . The aim of the present study was to evaluate the effects of preoperative hypnotic techniques used by patients planned for surgical removal of third m and ibular molars . The patients were r and omly assigned to an experimental ( hypnotic techniques ) or a control ( no hypnotic techniques ) group . During the week before the surgery , the experimental group listened to an audiotape containing a hypnotic relaxation induction . Posthypnotic suggestions of healing and recovery were given on the tape together with advice regarding ways to achieve control over stress and pain . The control group received no hypnotic intervention . Only one surgeon who was not aware of patient group assignments performed all the operations . Thirty-six patients in the control group were compared to 33 patients in the experimental group . Anxiety before the operation increased significantly in the control group but remained at baseline level in the experimental group . Postoperative consumption of analgesics was significantly reduced in the experimental group compared to the control group PURPOSE The aim of this study was to investigate whether brief psychologic interventions to reduce perioperative stress may improve the postoperative course of patients undergoing abdominal surgery . METHODS We used a r and omized , controlled , partially blinded trial to evaluate the differential effectiveness of two brief psychologic interventions ( guided imagery and progressive muscle relaxation ) on analgesic requirement , pain perception , pulmonary function , duration of postoperative ileus , and fatigue after conventional resection of colorectal carcinoma in elderly cancer patients . RESULTS Sixty patients ( 20 guided imagery , 22 relaxation , 18 control ) were evaluated . Acceptance of the brief psychologic interventions was high and 90 percent of the patients indicated that they would recommend it to other patients . Analgesic consumption ( P = 0.6 ) and subjective pain intensity at rest ( P = 0.3 ) and while coughing ( P = 0.3 ) were not different between groups . Recovery of pulmonary function , duration of postoperative ileus , and subjective postoperative fatigue were also not influenced . When the data from intervention groups were pooled , again no benefits were detected compared with the control group . CONCLUSIONS Brief psychologic interventions such as guided imagery and relaxation yielded a very positive patient response but did not show a clinical ly relevant influence on the postoperative physiologic course of elderly patients undergoing conventional resections of colorectal cancer Few studies have evaluated cognitive‐behavioral interventions as an adjunct treatment for chronic cancer‐related pain . A r and omized clinical trial was performed evaluating the efficacy of 3 brief cognitive‐behavioral techniques : relaxation , distraction , and positive mood interventions Background : This study was design ed to determine whether music ( M ) , or music in combination with therapeutic suggestions ( M/TS ) could improve the postoperative recovery in the immediate postoperative in daycare surgery & NA ; Stress reducing strategies are useful in patients undergoing surgery . Hypnosis is also known to alleviate acute and chronic pain . We therefore compared the effectiveness of these two psychological approaches for reducing perioperative discomfort during conscious sedation for plastic surgery . Sixty patients scheduled for elective plastic surgery under local anesthesia and intravenous sedation ( midazolam and alfentanil upon request ) were included in the study after providing informed consent . They were r and omly allocated to either stress reducing strategies ( control : CONT ) or hypnosis ( HYP ) during the entire surgical procedure . Both techniques were performed by the same anesthesiologist ( MEF ) . Patient behavior was noted during surgery by a psychologist , the patient noted anxiety , pain , perceived control before , during and after surgery , and postoperative nausea and vomiting ( PONV ) . Patient satisfaction and surgical conditions were also recorded . Peri‐ and postoperative anxiety and pain were significantly lower in the HYP group . This reduction in anxiety and pain were achieved despite a significant reduction in intraoperative requirements for midazolam and alfentanil in the HYP group ( alfentanil : 8.7±0.9 & mgr;g kg−1/h−1 vs. 19.4±2 & mgr;g kg−1/h−1 , P<0.001 ; midazolam : 0.04±0.003 mg kg−1/h−1 vs. 0.09±0.01 mg kg−1/h−1 , P<0.001 ) . Patients in the HYP group reported an impression of more intraoperative control than those in the CONT group ( P<0.01 ) . PONV were significantly reduced in the HYP group ( 6.5 % vs. 30.8 % , P<0.001 ) . Surgical conditions were better in the HYP group . Less signs of patient discomfort and pain were observed by the psychologist in the HYP group ( P<0.001 ) . Vital signs were significantly more stable in the HYP group . Patient satisfaction score was significantly higher in the HYP group ( P<0.004 ) . This study suggests that hypnosis provides better perioperative pain and anxiety relief , allows for significant reductions in alfentanil and midazolam requirements , and improves patient satisfaction and surgical conditions as compared with conventional stress reducing strategies support in patients receiving conscious sedation for plastic surgery OBJECTIVE The role of complementary medicine techniques has generated increasing interest in today 's society . The purpose of our study was to evaluate the effects of one technique , self-hypnosis , and its role in coronary artery bypass surgery . We hypotesize that self-hypnosis relaxation techniques will have a positive effect on the patient 's mental and physical condition following coronary artery bypass surgery . EXPERIMENTAL DESIGN A prospect i ve , r and omized trial was conducted . Patients were followed beginning one day prior to surgery until the time of discharge from the hospital . SETTING The study was conducted at Columbia Presbyterian Medical Center , a large tertiary care teaching institution . PATIENTS All patients undergoing first-time elective coronary artery bypass surgery were eligible . A total of 32 patients were r and omized into two groups . INTERVENTIONS The study group was taught self-hypnosis relaxation techniques preoperatively , with no therapy in the control group . MEASURES Outcome variables studied included anesthetic requirements , operative parameters , postoperative pain medication requirements , quality of life , hospital stay , major morbidity and mortality . RESULTS Patients who were taught self-hypnosis relaxation techniques were significantly more relaxed postoperatively compared to the control group ( p=0.032 ) . Pain medication requirements were also significantly less in patients practising the self-hypnosis relaxation techniques that those who were noncompliant ( p=0.046 ) . No differences were noted in intraoperative parameters , morbidity or mortality . CONCLUSION This study demonstrates the beneficial effects self-hypnosis relaxation techniques on patients undergoing coronary artery bypass surgery . It also provides a framework to study complementary techniques and the limitations encountered This experimental study compared the effects of jaw relaxation and music , individually and combined , on sensory and affective pain following surgery . Abdominal surgical patients ( N = 84 ) were r and omly assigned to four groups : relaxation , music , a combination of relaxation and music , and control . Interventions were taught preoperatively and used by subjects during the first ambulation after surgery . Indicators of the sensory component of pain were sensation and 24-hour narcotic intake . Indicator of the affective component of pain were distress and anxiety of pain . With preambulatory sensation , distress , narcotic intake , and preoperative anxiety as covariates , the four groups were compared using orthogonal a priori contrasts and analysis of covariance . The interventions were neither effective nor significantly different from one another during ambulation . However , after keeping the taped interventions for 2 postoperative days , 89 % of experimental subjects reported them helpful for sensation and distress of pain OBJECTIVE Postoperative pain is caused by surgical injury and trauma ; is stressful to patients ; and includes a series of physiologic , psychological , and behavioral reactions . Effective postoperative analgesia helps improve postoperative pain , perioperative safety , and hospital discharge rates . This study aim ed to observe the influence of postoperative intravenous sufentanil patient-controlled analgesia combined with music therapy versus sufentanil alone on hemodynamics and analgesia in patients with lung cancer . METHODS This was a r and omized parallel study performed in 60 patients in American Society of Anesthesiologists class I or II undergoing lung cancer resection at the Affiliated Cancer Hospital of Xiangya School of Medicine , Central South University . Patients were r and omly assigned to a music therapy ( MT ) group and a control ( C ) group . The MT group underwent preoperative and postoperative music intervention while the C group did not . Both groups received intravenous patient-controlled sufentanil analgesia . The primary outcome was the visual analogue scale ( VAS ) score at 24 hours after surgery . The secondary outcomes included hemodynamic changes ( systolic blood pressure , diastolic blood pressure , heart rate ) , changes on the Self-Rating Anxiety Scale ( SAS ) , total consumption of sufentanil , number of uses , sedation , and adverse effects . The postoperative sufentanil dose and analgesia frequency were recorded . RESULTS Compared with the C group , the MT group had significantly lower VAS score , systolic and diastolic blood pressure , heart rate , and SAS score within 24 hours after surgery ( p < 0.01 ) . In addition , postoperative analgesia frequency and sufentanil dose were reduced in the MT group ( p < 0.01 ) . CONCLUSIONS Combined music therapy and sufentanil improves intravenous patient-controlled analgesia effects compared with sufentanil alone after lung cancer surgery . Lower doses of sufentanil could be administered to more effectively improve patients ' cardiovascular parameters As medical costs continue to escalate , there is willingness to consider the role played by nontraditional factors in health . We investigated the usefulness of tape-recorded hypnosis instruction on perioperative outcome in surgical patients in a prospect i ve , r and omized , and partially blinded study . Sixty patients scheduled for third molar surgery were studied . Patients were allocated to either an experimental group ( E ) or a control group ( C ) . Group E received an audio tape to listen to daily for the immediate preoperative week , which guided the patients through a hypnotic induction and included suggestions on enhancement of perioperative well-being . Group C did not receive any tapes . The same surgeon administered local anesthesia and a st and ard regimen of sedation and performed the operation for all patients . The following variables were assessed 1 wk before surgery , immediately before and after surgery , and for 3 days after surgery by the indicated measurements : State anxiety by a Spielberger scale ; nausea and pain by visual analog scales ; number of tablets of the analgesics that were used ; number of episodes of vomiting ; and complications . In addition , the surgeon ’s assessment of ease of surgery was recorded . Two variables showed differences between the groups . First , Group C exhibited a mean increase of 11.7 points on the Spielberger scale from the screening to the presurgery period , while Group E showed only a mean increase of 5.5 points during the same period , P = 0.01 . Second , the mean number of vomiting episodes was more in Group E , 1.3 , than in Group C , 0.3 , P = 0.02 . In conclusion , anxiety was reduced before surgery by means of an audio tape containing hypnotic instructions ; however , for no apparent reason , there was also an increase in the incidence of vomiting . Implication s We administered hypnosis instructions to patients before third molar surgery . Anxiety was reduced , but there was an increase in the incidence of vomiting . Although an easy and cost-effective method , the value of this approach remains to be established PURPOSE : Guided imagery uses the power of thought to influence psychologic and physiologic states . Some studies have shown that guided imagery can decrease anxiety , analgesic requirements , and length of stay for surgical patients . This study was design ed to determine whether guided imagery in the perioperative period could improve the outcome of colorectal surgery patients . METHODS : We conducted a prospect i ve , r and omized trial of patients undergoing their first elective colorectal surgery at a tertiary care center . Patients were r and omly assigned into one of two groups . Group 1 received st and ard perioperative care , and Group 2 listened to a guided imagery tape three days preoperatively ; a music-only tape during induction , during surgery , and postoperatively in the recovery room ; a guided imagery tape during each of the first six postoperative days . Both groups had postoperative patient-controlled analgesia . All patients rated their levels of pain and anxiety daily , on a linear analog scale of 0 to 100 . Total narcotic consumption , time to first bowel movement , length of stay , and number of patients with complications were also recorded . RESULTS : Groups were similar in age and gender distribution , diagnoses , and surgery performed . Median baseline anxiety score was 75 in both groups . Before surgery , anxiety increased in the control group but decreased in the guided imagery group ( median change , 30;P < 0.001 ) . Postoperatively , median increase in the worst pain score was 72.5 for the control group and 42.5 for the imagery group ( P<0.001 ) . Least pain was also significantly different ( P<0.001 ) , with a median increase of 30 for controls and 12.5 for the imagery group . Total opioid requirements were significantly lower in the imagery group , with a median of 185 mgvs.326 mg in the control group ( P<0.001 ) . Time to first bowel movement was significantly less in the imagery group ( median , 58 hours ) than in the control group ( median , 92 hours;P<0.001 ) . The number of patients experiencing postoperative complications ( nausea , vomiting , pruritus , or ileus ) did not differ in the two groups . CONCLUSION : Guided imagery significantly reduces postoperative anxiety , pain , and narcotic requirements of colorectal surgery and increases patient satisfaction . Guided imagery is a simple and low-cost adjunct in the care of patients undergoing elective colorectal surgery The authors evaluated whether self-hypnotic relaxation can reduce the need for intravenous conscious sedation during interventional radiological procedures . Sixteen patients were r and omized to a test group , and 14 patients were r and omized to a control group . All had patient-controlled analgesia . Test patients additionally had self-hypnotic relaxation and underwent a Hypnotic Induction Profile test . Compared to controls , test patients used less drugs ( 0.28 vs. 2.01 drug units ; p < .01 ) and reported less pain ( median pain rating 2 vs. 5 on a 0 - 10 scale ; p < .01 ) . Significantly more control patients exhibited oxygen desaturation and /or needed interruptions of their procedures for hemodynamic instability . Benefit did not correlate with hypnotizability . Self-hypnotic relaxation can reduce drug use and improve procedural safety IMPORTANCE Mindfulness-based stress reduction ( MBSR ) has not been rigorously evaluated for young and middle-aged adults with chronic low back pain . OBJECTIVE To evaluate the effectiveness for chronic low back pain of MBSR vs cognitive behavioral therapy ( CBT ) or usual care . DESIGN , SETTING , AND PARTICIPANTS R and omized , interviewer-blind , clinical trial in an integrated health care system in Washington State of 342 adults aged 20 to 70 years with chronic low back pain enrolled between September 2012 and April 2014 and r and omly assigned to receive MBSR ( n = 116 ) , CBT ( n = 113 ) , or usual care ( n = 113 ) . INTERVENTIONS CBT ( training to change pain-related thoughts and behaviors ) and MBSR ( training in mindfulness meditation and yoga ) were delivered in 8 weekly 2-hour groups . Usual care included whatever care participants received . MAIN OUTCOMES AND MEASURES Co primary outcomes were the percentages of participants with clinical ly meaningful ( ≥30 % ) improvement from baseline in functional limitations ( modified Rol and Disability Question naire [ RDQ ] ; range , 0 - 23 ) and in self-reported back pain bothersomeness ( scale , 0 - 10 ) at 26 weeks . Outcomes were also assessed at 4 , 8 , and 52 weeks . RESULTS There were 342 r and omized participants , the mean ( SD ) [ range ] age was 49.3 ( 12.3 ) [ 20 - 70 ] years , 224 ( 65.7 % ) were women , mean duration of back pain was 7.3 years ( range , 3 months-50 years ) , 123 ( 53.7 % ) attended 6 or more of the 8 sessions , 294 ( 86.0 % ) completed the study at 26 weeks , and 290 ( 84.8 % ) completed the study at 52 weeks . In intent-to-treat analyses at 26 weeks , the percentage of participants with clinical ly meaningful improvement on the RDQ was higher for those who received MBSR ( 60.5 % ) and CBT ( 57.7 % ) than for usual care ( 44.1 % ) ( overall P = .04 ; relative risk [ RR ] for MBSR vs usual care , 1.37 [ 95 % CI , 1.06 - 1.77 ] ; RR for MBSR vs CBT , 0.95 [ 95 % CI , 0.77 - 1.18 ] ; and RR for CBT vs usual care , 1.31 [ 95 % CI , 1.01 - 1.69 ] ) . The percentage of participants with clinical ly meaningful improvement in pain bothersomeness at 26 weeks was 43.6 % in the MBSR group and 44.9 % in the CBT group , vs 26.6 % in the usual care group ( overall P = .01 ; RR for MBSR vs usual care , 1.64 [ 95 % CI , 1.15 - 2.34 ] ; RR for MBSR vs CBT , 1.03 [ 95 % CI , 0.78 - 1.36 ] ; and RR for CBT vs usual care , 1.69 [ 95 % CI , 1.18 - 2.41 ] ) . Findings for MBSR persisted with little change at 52 weeks for both primary outcomes . CONCLUSIONS AND RELEVANCE Among adults with chronic low back pain , treatment with MBSR or CBT , compared with usual care , result ed in greater improvement in back pain and functional limitations at 26 weeks , with no significant differences in outcomes between MBSR and CBT . These findings suggest that MBSR may be an effective treatment option for patients with chronic low back pain . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01467843 Abstract Pain following traumatic injuries is common , can impair injury recovery and is often inadequately treated . In particular , the role of adjunctive nonpharmacologic analgesic techniques is unclear . The authors report a r and omized , controlled study of 21 hospitalized trauma patients to assess the analgesic efficacy of virtual reality hypnosis (VRH)—hypnotic induction and analgesic suggestion delivered by customized virtual reality ( VR ) hardware/software . Subjective pain ratings were obtained immediately and 8 hours after VRH ( used as an adjunct to st and ard analgesic care ) and compared to both adjunctive VR without hypnosis and st and ard care alone . VRH patients reported less pain intensity and less pain unpleasantness compared to control groups . These preliminary findings suggest that VRH analgesia is a novel technology worthy of further study , both to improve pain management and to increase availability of hypnotic analgesia to population s without access to therapist-provided hypnosis and suggestion New strategies are needed to improve access to cognitive and behavioral therapies for patients with persistent pain . The purpose of this r and omized , controlled trial was to determine the effectiveness of the Chronic Pain Management Program , an 8-week online intervention targeting cognitive , emotional , behavioral , and social pain determinants . Program efficacy and engagement was evaluated for 92 individuals with a diagnosis of chronic noncancer pain who had a current opioid prescription . Participants were recruited from primary care practice s and Internet sites , then r and omly assigned to receive access to the intervention either immediately ( treatment group ) or after an 8-week delay ( wait-list comparison ) . Biweekly self-report measurements were collected using online surveys on pain , depressive symptoms , pain self-management behaviors , and health care utilization during the 8-week trial . Additional measurements of opioid misuse behaviors , pain self-efficacy , and medicine regimens were completed at baseline and week 8 . Engagement was evaluated by examining completion of program learning modules . The results from analysis of variance showed that at week 8 , the treatment group had significantly greater improvements on pain self-efficacy and opioid misuse measures than the wait-list comparison group . Engagement level was positively associated with improvements in pain intensity , pain interference , and pain self-efficacy . In conclusion , patients on opioids were able to engage and demonstrate positive outcomes using an Internet-based self-management program . Future efforts toward heightening engagement could further maximize impacts The United States is experiencing an epidemic of prescription opioid misuse , with prescription opioid overdose deaths more than quadrupling between 1999 and 2015 ( 14 ) . Misuse is defined as use of a psychotropic medication without a prescription ; for a reason other than as directed by a physician ; or in greater amounts , more often , or longer than prescribed . The potential for misuse complicates prescription of opioids ( 5 , 6 ) . Several studies based on local data ( 711 ) or national sample s of high school seniors ( 12 , 13 ) have examined motivations for medication misuse . However , an examination of the prevalence of prescription opioid use , misuse , and use disorders and motivations for misuse in the U.S. adult population has been lacking . Such data could inform efforts to reduce prescription opioid misuse and related morbidity and mortality . Based on a nationally representative sample of U.S. adults , this study examined the 12-month prevalence of prescription opioid use by sociodemographic characteristics , health conditions , and behavioral health status ; the prevalence of misuse and use disorders among prescription opioid users by sociodemographic characteristics , health conditions , and behavioral health status ; motivations for misuse ; and sources of prescription opioids among adults with misuse and use disorders . Methods Survey Methods and Study Population The 2015 National Survey on Drug Use and Health ( NSDUH ) was a face-to-face household interview survey conducted by the Substance Abuse and Mental Health Services Administration ( SAMHSA ) . The NSDUH used a stratified , multistage area probability sample that was design ed to be representative of the nation as a whole as well as each of the 50 states and the District of Columbia . Under a stratified design , with states serving as the primary strata and state sampling regions serving as the secondary strata , census tracts , census block groups , segments within census block groups , and dwelling units within segments were selected using probability-proportional-to-size sampling . After dwelling units were selected , an interviewer visited each unit to obtain a roster of all persons residing there . The roster information obtained from an eligible member of the dwelling unit was used to select 0 to 2 people for the survey . Data collection for NSDUH was approved by the Institutional Review Board at RTI International . Data were collected by interviewers in personal visits to households and noninstitutional group quarters . Each participant provided verbal informed consent . The interview lasted about an hour , and each respondent received $ 30 in cash after completion ( 14 ) . The NSDUH collected nationally representative data on prescription opioid use , misuse , and use disorders and motivations for misuse among the U.S. civilian , noninstitutionalized population aged 12 years or older ( 14 ) . Additional details about the NSDUH survey methods and question naire are available at SAMHSA 's Web site ( 14 ) . The NSDUH collected data using audio computer-assisted self-interviewing , in which respondents read or listened to the questions on headphones and then entered their answers directly into a laptop computer . This interview technique is design ed for accurate reporting of information by providing respondents with a private , confidential way to record answers to sensitive questions . The NSDUH also used computer-assisted personal interviewing , in which interviewers read less sensitive questions to respondents and entered answers into the laptop computer . In 2015 , the NSDUH screening process ( in which an interviewer visited each selected dwelling unit to obtain a roster of all persons residing there ) was completed at 132210 addresses , and the weighted screening response rate was 79.7 % , which was not specific to age groups ( 14 ) . The weighted interview response rate was 68.4 % for adults , based on the definitions of the American Association for Public Opinion Research ( 15 ) . A total of 72600 eligible persons aged 18 years or older were selected for the 2015 NSDUH , and 51200 completed the survey interview . Measures of Main Outcomes and Patient Characteristics The 2015 NSDUH asked about lifetime and past-year use and misuse of prescription opioids . The NSDUH defined prescription opioid misuse as in any way that a doctor did not direct you to use them , including 1 ) use without a prescription of your own ; 2 ) use in greater amounts , more often , or longer than you were told to take them ; or 3 ) use in any other way a doctor did not direct you to use them ( 16 ) . Past-year prescription opioid use disorder was defined on the basis of the 11 diagnostic criteria for prescription opioid dependence or abuse specified in the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) , including withdrawal ; tolerance ; use in dangerous situations ; trouble with the law ; and interference with major obligations at work , school , or home ( 17 ) . For respondents who reported prescription opioid misuse in the past year , NSDUH asked about the main motivation for the most recent episode with multiple-choice questions that offered the following options : to relieve physical pain , to relax or relieve tension , to experiment or see what the drug was like , to feel good or get high , to help with sleep , to help with feelings or emotions , to increase or decrease the effects of other drugs , because the respondent was hooked or had to have it , or other reason ( 16 ) . The source of prescription opioids for the most recent episode of misuse was assessed with a multiple-choice question that offered the following options : obtained from a friend or relative for free ; prescribed by a physician ; stolen from a friend or relative ; bought from a friend or relative ; bought from a drug dealer or stranger ; or stolen from a physician 's office , clinic , or pharmacy . If respondents reported that they obtained the prescription opioids from a friend or relative for free , NSDUH asked them where the friend or relative had obtained the opioids . In addition to sociodemographic characteristics ( age , sex , race/ethnicity , educational attainment , employment status , family income , marital status , health insurance , metropolitan statistical area , and census region ) , NSDUH asked respondents about lifetime and past-year use of tobacco , alcohol , cannabis , cocaine , heroin , hallucinogens , and inhalants as well as lifetime and past-year use and misuse of prescription sedatives , tranquilizers , and stimulants . Using survey items assessing DSM-IV diagnostic criteria , the NSDUH estimated prevalence in the past 12 months of major depressive episode and substance use disorders ( alcohol , cannabis , cocaine , heroin , hallucinogens , inhalants , prescription tranquilizers or sedatives , and prescription stimulants ) in addition to prescription opioid use disorders ( 17 ) . Nicotine dependence among cigarette smokers was assessed using the Nicotine Dependence Syndrome Scale ( 18 ) . These measures of substance use and use disorders have demonstrated good validity and reliability ( 1921 ) . For example , the 2006 NSDUH Reliability Study reported that the coefficient ( a st and ard measure of testretest agreement ) was 0.73 for prescription opioid misuse and 0.62 for illicit drug use disorders , suggesting good to excellent reliability ( 21 ) . Furthermore , a clinical validation study reported sensitivity of 0.85 and specificity of 0.75 for illicit drug use disorders ( including prescription opioid use disorder ) ( 20 ) . Finally , the survey asked about medical diagnoses received from a physician or other health care professional ( hypertension , heart disease , diabetes mellitus , chronic obstructive pulmonary disease , asthma , cancer , HIV/AIDS , hepatitis B or C , cirrhosis , and kidney disease ) , respondents ' self-rated health , and the number of emergency department visits in the prior year . Among the 2015 NSDUH adult participants , item response rates were high ( for example , > 99 % for the prescription opioid misuse and use disorder variables ) . Furthermore , missing values are imputed in NSDUH using predictive mean neighborhoods ( 22 , 23 ) , a combination of a model-assisted imputation method and a r and om nearest-neighbor hot-deck procedure . For prescription opioid use , misuse , and use disorders ( the main variables of this study ) , a modified version of predictive mean neighborhoods was used to cycle through a group of variables being imputed as a set ( 23 ) . Statistical Analysis We estimated the national 12-month prevalence of prescription opioid use overall and by sociodemographic , health , and behavioral health characteristics . Next , among adults with prescription opioid use in the past 12 months , we estimated the national 12-month prevalence of prescription opioid misuse and use disorders overall and by sociodemographic , health , and behavioral health characteristics . Finally , we assessed the main motivations and the sources of prescription opioids for the most recent episode of misuse . We used SUDAAN software ( RTI International ) ( 24 ) to account for the complex sample design and sample weights of NSDUH . The NSDUH weighting procedures adjusted for nonresponse through direct adjustments as well as an indirect adjustment via poststratification ( 25 ) . Institutional Review Board Approval The NSDUH data collection protocol was approved by the U.S. Office of Management and Budget and the Institutional Review Board at RTI International . Role of the Funding Source The funding sources supported the authors , who were responsible for preparation , review , and approval of the manuscript and the decision to su bmi t the manuscript for publication . The funding sources had no role in the design and conduct of the study , analysis and interpretation of the data , preparation and review of the manuscript , or the decision to su bmi t the manuscript for publication . The funding sources review ed and approved the manuscript . Results National Prevalence of Prescription Opioid Use , Misuse , and Use Disorders On the basis of the 51200 adult |
13,536 | 32,163,853 | Taken together , dose-reduced chemoradiotherapy ( with or without induction chemotherapy for patient/biology selection purpose s ) seems to be a promising de-escalation strategy for HPV-associated OPC , although replacement of concurrent cisplatin by cetuximab is not recommended . | Numerous trials have been launched over the prior decade examining the safety and efficacy of therapy de-escalation in human papillomavirus (HPV)-associated oropharyngeal cancer ( OPC ) .
Because no summative assessment of these prospect i ve trials exists to date , we systematic ally review ed the outcomes and toxicities associated with therapy de-intensification for this population . | BACKGROUND Oropharyngeal squamous-cell carcinomas caused by human papillomavirus ( HPV ) are associated with favorable survival , but the independent prognostic significance of tumor HPV status remains unknown . METHODS We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a r and omized trial comparing accelerated-fractionation radiotherapy ( with acceleration by means of concomitant boost radiotherapy ) with st and ard-fractionation radiotherapy , each combined with cisplatin therapy , in patients with squamous-cell carcinoma of the head and neck . Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer . RESULTS The median follow-up period was 4.8 years . The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving st and ard-fractionation radiotherapy ( 70.3 % vs. 64.3 % ; P=0.18 ; hazard ratio for death with accelerated-fractionation radiotherapy , 0.90 ; 95 % confidence interval [ CI ] , 0.72 to 1.13 ) , as were the rates of high- grade acute and late toxic events . A total of 63.8 % of patients with oropharyngeal cancer ( 206 of 323 ) had HPV-positive tumors ; these patients had better 3-year rates of overall survival ( 82.4 % , vs. 57.1 % among patients with HPV-negative tumors ; P<0.001 by the log-rank test ) and , after adjustment for age , race , tumor and nodal stage , tobacco exposure , and treatment assignment , had a 58 % reduction in the risk of death ( hazard ratio , 0.42 ; 95 % CI , 0.27 to 0.66 ) . The risk of death significantly increased with each additional pack-year of tobacco smoking . Using recursive-partitioning analysis , we classified our patients as having a low , intermediate , or high risk of death on the basis of four factors : HPV status , pack-years of tobacco smoking , tumor stage , and nodal stage . CONCLUSIONS Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer . ( Clinical Trials.gov number , NCT00047008 . The purpose of the current study was to determine quality of life and tumor control from a prospect i ve phase 2 clinical trial evaluating deintensified chemoradiotherapy for favorable risk , human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma Purpose Chemoradiation with cisplatin 100 mg/m2 given once every 3 weeks is the st and ard of care in locally advanced head and neck squamous cell cancer ( LAHNSCC ) . Increasingly , low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience . However , there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks . Patients and Methods In this phase III r and omized trial , we assessed the noninferiority of cisplatin 30 mg/m2 given once a week compared with cisplatin 100 mg/m2 given once every 3 weeks , both administered concurrently with curative intent radiotherapy in patients with LAHNSCC . The primary end point was locoregional control ( LRC ) ; secondary end points included toxicity , compliance , response , progression-free survival , and overall survival . Results Between 2013 and 2017 , we r and omly assigned 300 patients , 150 to each arm . Two hundred seventy-nine patients ( 93 % ) received chemoradiotherapy in the adjuvant setting . At a median follow-up of 22 months , the estimated cumulative 2-year LRC rate was 58.5 % in the once-a-week arm and 73.1 % in the once-every-3-weeks arm , leading to an absolute difference of 14.6 % ( 95 % CI , 5.7 % to 23.5 % ) ; P = .014 ; hazard ratio ( HR ) , 1.76 ( 95 % CI , 1.11 to 2.79 ) . Acute toxicities of grade 3 or higher occurred in 71.6 % of patients in the once-a-week arm and in 84.6 % of patients in the once-every-3-weeks arm ( P = .006 ) . Estimated median progression-free survival in the once-a-week arm was 17.7 months ( 95 % CI , 0.42 to 35.05 months ) and in the once-every-3-weeks arm , 28.6 months ( 95 % CI , 15.90 to 41.30 months ) ; HR , 1.24 ( 95 % CI , 0.89 to 1.73 ) ; P = .21 . Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm ( HR , 1.14 [ 95 % CI , 0.79 to 1.65 ] ; P = .48 ) . Conclusion Once-every-3-weeks cisplatin at 100 mg/m2 result ed in superior LRC , albeit with more toxicity , than did once-a-week cisplatin at 30 mg/m2 , and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting BACKGROUND The relative efficacy of the addition of induction chemotherapy to chemoradiotherapy compared with chemoradiotherapy alone for patients with head and neck cancer is unclear . The PARADIGM study is a multicentre open-label phase 3 study comparing the use of docetaxel , cisplatin , and fluorouracil ( TPF ) induction chemotherapy followed by concurrent chemoradiotherapy with cisplatin-based concurrent chemoradiotherapy alone in patients with locally advanced head and neck cancer . METHODS Adult patients with previously untreated , non-metastatic , newly diagnosed head and neck cancer were eligible . Patients were eligible if their tumour was either unresectable or of low surgical curability on the basis of advanced tumour stage ( 3 or 4 ) or regional-node stage ( 2 or 3 , except T1N2 ) , or if they were a c and i date for organ preservation . Patients were r and omly assigned ( in a 1:1 ratio ) to receive either induction chemotherapy with three cycles of TPF followed by concurrent chemoradiotherapy with either docetaxel or carboplatin or concurrent chemoradiotherapy alone with two cycles of bolus cisplatin . A computer-generated r and omisation schedule using minimisation was prepared and the treatment assignment was done central ly at one of the study sites . Patients , study staff , and investigators were not masked to group assignment . Stratification factors were WHO performance status , primary disease site , and stage . The primary endpoint was overall survival . Analysis was by intention to treat . Patient accrual was terminated in December , 2008 , because of slow enrolment . The trial is registered with Clinical Trials.gov , number NCT00095875 . FINDINGS Between Aug 24 , 2004 , and Dec 29 , 2008 , we enrolled 145 patients across 16 sites . After a median follow-up of 49 months ( IQR 39 - 63 ) , 41 patients had died-20 in the induction chemotherapy followed by chemoradiotherapy group and 21 in the chemoradiotherapy alone group . 3-year overall survival was 73 % ( 95 % CI 60 - 82 ) in the induction therapy followed by chemoradiotherapy group and 78 % ( 66 - 86 ) in the chemoradiotherapy alone group ( hazard ratio 1·09 , 95 % CI 0·59 - 2·03 ; p=0·77 ) . More patients had febrile neutropenia in the induction chemotherapy followed by chemoradiotherapy group ( 16 patients ) than in the chemoradiotherapy alone group ( one patient ) . INTERPRETATION Although survival results were good in both groups there was no difference noted between those patients treated with induction chemotherapy followed by chemoradiotherapy and those who received chemoradiotherapy alone . We can not rule out the possibility of a difference in survival going undetected due to early termination of the trial . Clinicians should still use their best judgment , based on the available data , in the decision of how to best treat patients . The addition of induction chemotherapy remains an appropriate approach for advanced disease with high risk for local or distant failure . FUNDING Sanofi-Aventis PURPOSE Induction chemotherapy ( IC ) before radiotherapy lowers distant failure ( DF ) rates in locally advanced squamous cell carcinoma of the head and neck ( SCCHN ) . The goal of this phase III trial was to determine whether IC before chemoradiotherapy ( CRT ) further improves survival compared with CRT alone in patients with N2 or N3 disease . PATIENTS AND METHODS Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were r and omly assigned to CRT alone ( CRT arm ; docetaxel , fluorouracil , and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week ) versus two 21-day cycles of IC ( docetaxel 75 mg/m(2 ) on day 1 , cisplatin 75 mg/m(2 ) on day 1 , and fluorouracil 750 mg/m(2 ) on days 1 to 5 ) followed by the same CRT regimen ( IC + CRT arm ) . The primary end point was overall survival ( OS ) . Secondary end points included DF-free survival , failure pattern , and recurrence-free survival ( RFS ) . RESULTS A total of 285 patients were r and omly assigned . The most common grade 3 to 4 toxicities during IC were febrile neutropenia ( 11 % ) and mucositis ( 9 % ) ; during CRT ( both arms combined ) , they were mucositis ( 49 % ) , dermatitis ( 21 % ) , and leukopenia ( 18 % ) . Serious adverse events were more common in the IC arm ( 47 % v 28 % ; P = .002 ) . With a minimum follow-up of 30 months , there were no statistically significant differences in OS ( hazard ratio , 0.91 ; 95 % CI , 0.59 to 1.41 ) , RFS , or DF-free survival . CONCLUSION IC did not translate into improved OS compared with CRT alone . However , the study was underpowered because it did not meet the planned accrual target , and OS was higher than predicted in both arms . IC can not be recommended routinely in patients with N2 or N3 locally advanced SCCHN BACKGROUND Concurrent chemoradiotherapy ( CCRT ) is the st and ard treatment for patients with unresectable , nonmetastatic locoregionally advanced squamous-cell carcinoma of the head and neck ( LASCCHN ) . This r and omized , open-label , phase III clinical trial compared the efficacy between st and ard CCRT and two different induction chemotherapy ( ICT ) regimens followed by CCRT . PATIENTS AND METHODS Patients with untreated LASCCHN were r and omly assigned to ICT ( three cycles ) , with either docetaxel ( Taxotere ) , cisplatin and 5-fluorouracil ( TPF arm ) or cisplatin and 5-fluorouracil ( PF arm ) , followed by CCRT [ 7 weeks of radiotherapy ( RT ) with cisplatin 100 mg/m(2 ) on days 1 , 22 and 43 ] ; or 7 weeks of CCRT alone . The primary end points were progression-free survival ( PFS ) and time-to-treatment failure ( TTF ) . RESULTS In the intention-to-treat ( ITT ) population ( n = 439 ) , the median PFS times were 14.6 ( 95 % CI , 11.6 - 20.4 ) , 14.3 ( 95 % CI , 11.8 - 19.3 ) and 13.8 months ( 95 % CI , 11.0 - 17.5 ) at TPF-CCRT , PF-CCRT and CCRT arms , respectively ( log-rank P = 0.56 ) . The median TTF were 7.9 ( 95 % CI , 5.9 - 11.8 ) , 7.9 ( 95 % CI , 6.5 - 11.8 ) and 8.2 months ( 95 % CI , 6.7 - 12.6 ) for TPF-CCRT , PF-CCRT and CCRT alone , respectively ( log-rank P = 0.90 ) . There were no statistically significant differences for overall survival ( OS ) . Toxic effects from ICT-CCRT were manageable . CONCLUSION Overall , this trial failed to show any advantage of ICT-CCRT over CCRT alone in patients with unresectable LASCCHN Purpose Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma ( OPSCC ) is treatment-responsive . Definitive chemoradiation results in high cure rates but causes long-term toxicity and may represent overtreatment of some patients . This phase II trial evaluated whether complete clinical response ( cCR ) to induction chemotherapy ( IC ) could select patients with HPV-associated OPSCC for reduced radiation dose as a means of sparing late sequelae . Methods Patients with HPV16 and /or p16-positive , stage III-IV OPSCC received three cycles of IC with cisplatin , paclitaxel , and cetuximab . Patients with primary -site cCR to IC received intensity-modulated radiation therapy ( IMRT ) 54 Gy with weekly cetuximab ; those with less than cCR to IC at the primary site or nodes received 69.3 Gy and cetuximab to those regions . The primary end point was 2-year progression-free survival . Results Of the 90 patients enrolled , 80 were evaluable . Their median age was 57 years ( range , 35 to 73 years ) , with the majority having stage T1 - 3N0-N2b OPSCC and a history of ≤ 10 pack-years of cigarette smoking . Three cycles of IC were delivered to 77 of the 80 patients . Fifty-six patients ( 70 % ) achieved a primary -site cCR to IC and 51 patients continued to cetuximab with IMRT 54 Gy . After median follow-up of 35.4 months , 2-year progression-free survival and overall survival rates were 80 % and 94 % , respectively , for patients with primary -site cCR treated with 54 Gy of radiation ( n = 51 ) ; 96 % and 96 % , respectively , for patients with < T4 , < N2c , and ≤ 10 pack-year smoking history who were treated with ≤ 54 Gy of radiation ( n = 27 ) . At 12 months , significantly fewer patients treated with a radiation dose ≤ 54 Gy had difficulty swallowing solids ( 40 % v 89 % ; P = .011 ) or had impaired nutrition ( 10 % v 44 % ; P = .025 ) . Conclusion For IC responders , reduced-dose IMRT with concurrent cetuximab is worthy of further study in favorable-risk patients with HPV-associated OPSCC . Radiation dose reduction result ed in significantly improved swallowing and nutritional status PURPOSE To report a small sub study of an ongoing large , multi-arm study using functional imaging to assess pre-/intratreatment hypoxia for all head and neck cancer , in which we hypothesized that pre- and early-treatment hypoxia assessment using functional positron emission tomography ( PET ) imaging may help select which human papillomavirus (HPV)-positive ( HPV(+ ) ) oropharyngeal cancer ( OPC ) patients can safely receive radiation de-escalation without jeopardizing treatment outcomes . METHODS AND MATERIAL S Patients with HPV(+ ) oropharyngeal carcinoma were enrolled on an institutional review board-approved prospect i ve study of which de-escalation based on imaging response was done for node(s ) only . Pretreatment (18)F-fluorodeoxyglucose and dynamic (18)F-FMISO ( fluoromisonidazole ) positron emission tomography ( PET ) scans were performed . For patients with pretreatment hypoxia on(18)F-FMISO PET ( defined as a > 1.2 tumor to muscle st and ard uptake value ratio ) , a repeat scan was done 1 week after chemoradiation . Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10-Gy dose reduction to metastatic lymph node(s ) . The 2-year local , regional , distant metastasis-free , and overall survival rates were estimated using the Kaplan-Meier product-limit method . A subset of patients had biopsy of a hypoxic node done under image guidance . RESULTS Thirty-three HPV(+ ) OPC patients were enrolled in this pilot study . One hundred percent showed pretreatment hypoxia ( at primary site and /or node[s ] ) , and among these , 48 % resolved ( at primary site and /or node[s ] ) ; 30 % met criteria and received 10-Gy reduction to the lymph node(s ) . At the median follow-up of 32 months ( range , 21 - 61 months ) , the 2-year locoregional control rate was 100 % . One patient failed distantly with persistence of hypoxia on (18)F-FMISO PET . The 2-year distant metastasis-free rate was 97 % . The 2-year OS rate was 100 % . Hypoxia on imaging was confirmed pathologically . CONCLUSIONS Hypoxia is present in HPV(+ ) tumors but resolves within 1 week of treatment in 48 % of cases either at the primary site and /or lymph node(s ) . Our 100 % locoregional control rate suggests that intratreatment functional imaging used to selectively de-escalate node(s ) to 60 Gy was confirmed safe using our stringent imaging criteria . Intratreatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies BACKGROUND Head and neck cancers positive for human papillomavirus ( HPV ) are exquisitely radiosensitive . We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma . METHODS We did a single-arm , phase 2 trial at two academic hospitals in the USA , enrolling patients with newly diagnosed , biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx , positive for HPV by p16 testing , and with Zubrod performance status scores of 0 or 1 . Patients received two cycles of induction chemotherapy with 175 mg/m2 paclitaxel and carboplatin ( target area under the curve of 6 ) given 21 days apart , followed by intensity-modulated radiotherapy with daily image guidance plus 30 mg/m2 paclitaxel per week concomitantly . Complete or partial responders to induction chemotherapy received 54 Gy in 27 fractions , and those with less than partial or no responses received 60 Gy in 30 fractions . The primary endpoint was progression-free survival at 2 years , assessed in all eligible patients who completed protocol treatment . This study is registered with Clinical Trials.gov , numbers NCT02048020 and NCT01716195 . FINDINGS Between Oct 4 , 2012 , and March 3 , 2015 , 45 patients were enrolled with a median age of 60 years ( IQR 54 - 67 ) . One patient did not receive treatment and 44 were included in the analysis . 24 ( 55 % ) patients with complete or partial responses to induction chemotherapy received 54 Gy radiation , and 20 ( 45 % ) with less than partial responses received 60 Gy . Median follow-up was 30 months ( IQR 26 - 37 ) . Three ( 7 % ) patients had locoregional recurrence and one ( 2 % ) had distant metastasis ; 2-year progression-free survival was 92 % ( 95 % CI 77 - 97 ) . 26 ( 39 % ) of 44 patients had grade 3 adverse events , but no grade 4 events were reported . The most common grade 3 events during induction chemotherapy were leucopenia ( 17 [ 39 % ] ) and neutropenia ( five [ 11 % ] ) , and during chemoradiotherapy were dysphagia ( four [ 9 % ] ) and mucositis ( four [ 9 % ] ) . One ( 2 % ) of 44 patients was dependent on a gastrostomy tube at 3 months and none was dependent 6 months after treatment . INTERPRETATION Chemoradiotherapy with radiation doses reduced by 15 - 20 % was associated with high progression-free survival and an improved toxicity profile compared with historical regimens using st and ard doses . Radiotherapy de-escalation has the potential to improve the therapeutic ratio and long-term function for these patients . FUNDING University of California BACKGROUND Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma have high survival when treated with radiotherapy plus cisplatin . Whether replacement of cisplatin with cetuximab-an antibody against the epidermal growth factor receptor-can preserve high survival and reduce treatment toxicity is unknown . We investigated whether cetuximab would maintain a high proportion of patient survival and reduce acute and late toxicity . METHODS RTOG 1016 was a r and omised , multicentre , non-inferiority trial at 182 health-care centres in the USA and Canada . Eligibility criteria included histologically confirmed HPV-positive oropharyngeal carcinoma ; American Joint Committee on Cancer 7th edition clinical categories T1-T2 , N2a-N3 M0 or T3-T4 , N0-N3 M0 ; Zubrod performance status 0 or 1 ; age at least 18 years ; and adequate bone marrow , hepatic , and renal function . We r and omly assigned patients ( 1:1 ) to receive either radiotherapy plus cetuximab or radiotherapy plus cisplatin . R and omisation was balanced by using r and omly permuted blocks , and patients were stratified by T category ( T1-T2 vs T3-T4 ) , N category ( N0-N2a vs N2b-N3 ) , Zubrod performance status ( 0 vs 1 ) , and tobacco smoking history ( ≤10 pack-years vs > 10 pack-years ) . Patients were assigned to receive either intravenous cetuximab at a loading dose of 400 mg/m2 5 - 7 days before radiotherapy initiation , followed by cetuximab 250 mg/m2 weekly for seven doses ( total 2150 mg/m2 ) , or cisplatin 100 mg/m2 on days 1 and 22 of radiotherapy ( total 200 mg/m2 ) . All patients received accelerated intensity-modulated radiotherapy delivered at 70 Gy in 35 fractions over 6 weeks at six fractions per week ( with two fractions given on one day , at least 6 h apart ) . The primary endpoint was overall survival , defined as time from r and omisation to death from any cause , with non-inferiority margin 1·45 . Primary analysis was based on the modified intention-to-treat approach , whereby all patients meeting eligibility criteria are included . This study is registered with Clinical Trials.gov , number NCT01302834 . FINDINGS Between June 9 , 2011 , and July 31 , 2014 , 987 patients were enrolled , of whom 849 were r and omly assigned to receive radiotherapy plus cetuximab ( n=425 ) or radiotherapy plus cisplatin ( n=424 ) . 399 patients assigned to receive cetuximab and 406 patients assigned to receive cisplatin were subsequently eligible . After median follow-up duration of 4·5 years , radiotherapy plus cetuximab did not meet the non-inferiority criteria for overall survival ( hazard ratio [ HR ] 1·45 , one-sided 95 % upper CI 1·94 ; p=0·5056 for non-inferiority ; one-sided log-rank p=0·0163 ) . Estimated 5-year overall survival was 77·9 % ( 95 % CI 73·4 - 82·5 ) in the cetuximab group versus 84·6 % ( 80·6 - 88·6 ) in the cisplatin group . Progression-free survival was significantly lower in the cetuximab group compared with the cisplatin group ( HR 1·72 , 95 % CI 1·29 - 2·29 ; p=0·0002 ; 5-year progression-free survival 67·3 % , 95 % CI 62·4 - 72·2 vs 78·4 % , 73·8 - 83·0 ) , and locoregional failure was significantly higher in the cetuximab group compared with the cisplatin group ( HR 2·05 , 95 % CI 1·35 - 3·10 ; 5-year proportions 17·3 % , 95 % CI 13·7 - 21·4 vs 9·9 % , 6·9 - 13·6 ) . Proportions of acute moderate to severe toxicity ( 77·4 % , 95 % CI 73·0 - 81·5 vs 81·7 % , 77·5 - 85·3 ; p=0·1586 ) and late moderate to severe toxicity ( 16·5 % , 95 % CI 12·9 - 20·7 vs 20·4 % , 16·4 - 24·8 ; p=0·1904 ) were similar between the cetuximab and cisplatin groups . INTERPRETATION For patients with HPV-positive oropharyngeal carcinoma , radiotherapy plus cetuximab showed inferior overall survival and progression-free survival compared with radiotherapy plus cisplatin . Radiotherapy plus cisplatin is the st and ard of care for eligible patients with HPV-positive oropharyngeal carcinoma . FUNDING National Cancer Institute USA , Eli Lilly , and The Oral Cancer Foundation Summary Background The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer , a disease affecting younger patients , is rapidly increasing . Cetuximab , an epidermal growth factor receptor inhibitor , has been proposed for treatment de-escalation in this setting to reduce the toxicity of st and ard cisplatin treatment , but no r and omised evidence exists for the efficacy of this strategy . Methods We did an open-label r and omised controlled phase 3 trial at 32 head and neck treatment centres in Irel and , the Netherl and s , and the UK , in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer ( non-smokers or lifetime smokers with a smoking history of < 10 pack-years ) . Eligible patients were r and omly assigned ( 1:1 ) to receive , in addition to radiotherapy ( 70 Gy in 35 fractions ) , either intravenous cisplatin ( 100 mg/m2 on days 1 , 22 , and 43 of radiotherapy ) or intravenous cetuximab ( 400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2 ) . The primary outcome was overall severe ( grade 3–5 ) toxicity events at 24 months from the end of treatment . The primary outcome was assessed by intention-to-treat and per- protocol analyses . This trial is registered with the IS RCT N registry , number IS RCT N33522080 . Findings Between Nov 12 , 2012 , and Oct 1 , 2016 , 334 patients were recruited ( 166 in the cisplatin group and 168 in the cetuximab group ) . Overall ( acute and late ) severe ( grade 3–5 ) toxicity did not differ significantly between treatment groups at 24 months ( mean number of events per patient 4·8 [ 95 % CI 4·2–5·4 ] with cisplatin vs 4·8 [ 4·2–5·4 ] with cetuximab ; p=0·98 ) . At 24 months , overall all- grade toxicity did not differ significantly either ( mean number of events per patient 29·2 [ 95 % CI 27·3–31·0 ] with cisplatin vs 30·1 [ 28·3–31·9 ] with cetuximab ; p=0·49 ) . However , there was a significant difference between cisplatin and cetuximab in 2-year overall survival ( 97·5 % vs 89·4 % , hazard ratio 5·0 [ 95 % CI 1·7–14·7 ] ; p=0·001 ) and 2-year recurrence ( 6·0 % vs 16·1 % , 3·4 [ 1·6–7·2 ] ; p=0·0007 ) . Interpretation Compared with the st and ard cisplatin regimen , cetuximab showed no benefit in terms of reduced toxicity , but instead showed significant detriment in terms of tumour control . Cisplatin and radiotherapy should be used as the st and ard of care for HPV-positive low-risk patients who are able to tolerate cisplatin . Funding Cancer Research UK BACKGROUND Human Papillomavirus oropharyngeal carcinoma ( HPVOPC ) has better progression free ( PFS ) and overall survival ( OS ) than non-HPVOPC . St and ard-dose chemoradiotherapy ( sdCRT ) results in significant acute toxicity and late morbidity . We hypothesized that after induction chemotherapy ( IC ) , reduced dose chemoradiation ( rdCRT ) would result in equivalent PFS and OS compared to sdCRT plus IC in HPVOPC and would reduce toxicity . METHODS Patients with p16 + , previously untreated , locally advanced HPVOPC and ≤20 pack years smoking history received 3 cycles of IC with docetaxel , cisplatin and fluorouracil ( TPF ) . Clinical responders who were HPV positive by type-specific PCR were r and omized 1:2 to sdCRT ( 7000 cGy ) or rdCRT ( 5600 cGy ) with weekly carboplatin . The endpoints of the study were 3 year PFS and OS . RESULTS 23 patients were enrolled , 22 were evaluable for TPF toxicity and 20 were r and omized , 8 to sdCRT and 12 to rdCRT . Sixteen ( 80 % ) were HPV 16 + and 4 ( 20 % ) were other high risk ( HR ) variants . Fourteen ( 70 % ) had high risk features : T4 , N2c , or N3 . Median follow up was 56 months ( range 42 - 70 ) . Three-year PFS/OS for sdCRT and rdCRT are 87.5 % vs 83.3 % ( log-rank test p = 0.85 ) , respectively . All 3 failures are locoregional within 4 months of completion of CRT ; 2 were in HR variants ( 50 % ) . CONCLUSIONS rdCRT after IC result ed in similar PFS/OS compared sdCRT . These data support Phase 3 clinical trials of radiation dose reduction after IC as a treatment strategy in HPVOPC . Molecular HPV with variant testing and smoking history are necessary for de-escalation trials |
13,537 | 27,695,301 | Results from single sessions of motivational interviewing showed no clear benefit on alcohol consumption outcomes , with few studies indicating benefit of PCC versus control .
Although the results for studies of multiple sessions of counseling were also mixed , many did show a significant benefit of the PCC intervention .
By contrast , studies consistently demonstrated a benefit of pharmacologically supported PCC interventions , with most of the differences reaching statistical significance .
IMPLICATION S PCC-based interventions may be beneficial for reducing alcohol consumption in people with alcohol use disorders | ISSUES Patient-centered care ( PCC ) is increasingly accepted as an integral component of good health care , including addiction medicine .
However , its implementation has been controversial in people with alcohol use disorders . | BACKGROUND Brief interventions for problem drinking in medical setting s are effective but rarely conducted , mainly due to insufficient time . A stepped care approach ( starting with a very brief intervention and intensifying efforts in case of no success ) could save re sources and enlarge effectiveness ; however , research is lacking . The present study compares a full care brief intervention for patients with at-risk drinking , alcohol abuse or dependence with a stepped care approach in a r and omized controlled trial . METHODS Participants were proactively recruited from general practice s in two northern German cities . In total , 10,803 screenings were conducted ( refusal rate : 5 % ) . Alcohol use disorders according to DSM-IV were assessed with the Munich-Composite International Diagnostic Interview ( M-CIDI ) . Eligible participants were r and omly assigned to one of three conditions : ( 1 ) stepped care ( SC ) : a computerized intervention plus up to three 40-min telephone-based interventions depending on the success of the previous intervention ; ( 2 ) full-care ( FC ) : a computerized intervention plus a fixed number of four 30-min telephone-based interventions that equals the maximum of the stepped care intervention ; ( 3 ) an untreated control group ( CG ) . Counseling effort in the intervention conditions and quantity/frequency of drinking were assessed at 12-month follow-up . RESULTS SC participants received roughly half of the amount of intervention in minutes compared to FC participants . Both groups did not differ in drinking outcomes . Compared to CG , intervention showed small to medium effect size for at-risk drinkers . CONCLUSIONS Study results reveal that a stepped care approach can be expected to increase cost-effectiveness of brief interventions for individuals with at-risk drinking AIM To establish the efficacy of a brief motivational intervention compared to feedback only when delivered in an emergency department for reducing alcohol use and problems among young adults . DESIGN Two-group r and omized controlled trial with follow-up assessment s at 6 and 12 months . SETTING Level I Trauma Center . PARTICIPANTS A total of 198 18 - 24-year-old patients who were either alcohol positive upon hospital admission or met screening criteria for alcohol problems . INTERVENTION Participants were assigned r and omly to receive a one-session motivational intervention ( MI ) that included personalized feedback , or the personalized feedback report only ( FO ) . All participants received additional telephone contact 1 month and 3 months after baseline . MEASUREMENTS Demographic information , alcohol use , alcohol problems and treatment seeking . FINDINGS Six months after the intervention MI participants drank on fewer days , had fewer heavy drinking days and drank fewer drinks per week in the past month than did FO patients . These effects were maintained at 12 months . Clinical significance evaluation indicated that twice as many MI participants as FO participants reliably reduced their volume of alcohol consumption from baseline to 12 months . Reductions in alcohol-related injuries and moving violations , and increases in alcohol treatment-seeking were observed across both conditions at both follow-ups with no differences between conditions . CONCLUSIONS This study provides new data supporting the potential of the motivational intervention tested to reduce alcohol consumption among high-risk youth BACKGROUND Risky driving and hazardous drinking are associated with significant human and economic costs . Brief interventions for more than one risky behavior have the potential to reduce health-compromising behaviors in population s with multiple risk-taking behaviors such as young adults . Emergency department ( ED ) visits provide a window of opportunity for interventions meant to reduce both risky driving and hazardous drinking . METHODS We determined the efficacy of a Screening , Brief Intervention , and Referral to Treatment ( SBIRT ) protocol addressing risky driving and hazardous drinking . We used a r and omized controlled trial design with follow-ups through 12 months . ED patients aged 18 to 44 who screened positive for both behaviors ( n = 476 ) were r and omized to brief intervention ( BIG ) , contact control ( CCG ) , or no-contact control ( NCG ) groups . The BIG ( n = 150 ) received a 20-minute assessment and two 20-minute interventions . The CCG ( n = 162 ) received a 20-minute assessment at baseline and no intervention . The NCG ( n = 164 ) were asked for contact information at baseline and had no assessment or intervention . Outcomes at 3 , 6 , 9 , and 12 months were self-reported driving behaviors and alcohol consumption . RESULTS Outcomes were significantly lower in BIG compared with CCG through 6 or 9 months , but not at 12 months : Safety belt use at 3 months ( adjusted odds ratio [ AOR ] , 0.22 ; 95 % confidence interval [ CI ] , 0.08 to 0.65 ) ; 6 months ( AOR , 0.13 ; 95 % CI , 0.04 to 0.42 ) ; and 9 months ( AOR , 0.18 ; 95 % CI , 0.06 to 0.56 ) ; binge drinking at 3 months ( adjusted rate ratio [ ARR ] 0.84 ; 95 % CI , 0.74 to 0.97 ) and 6 months ( ARR , 0.81 ; 95 % CI , 0.67 to 0.97 ) ; and ≥5 st and ard drinks/d at 3 months ( AOR , 0.43 ; 95 % CI , 0.20 to 0.91 ) and 6 months ( AOR , 0.41 ; 95 % CI , 0.17 to 0.98 ) . No substantial differences were observed between BIG and NCG at 12 months . CONCLUSIONS Our findings indicate that SBIRT reduced risky driving and hazardous drinking in young adults , but its effects did not persist after 9 months . Future research should explore methods for extending the intervention effect OBJECTIVE This study was design ed to conduct a r and omized controlled trial of motivational enhancement therapy ( MET ) with two control conditions : nondirective reflective listening ( NDRL ) and no further counseling ( NFC ) ; and to conduct this study in a sample of patients with a primary diagnosis of mild to moderate alcohol dependence , in a " real-life " clinical setting . METHOD Patients with mild to moderate alcohol dependence were recruited , assessed and treated at the Community Alcohol and Drug Service of Christchurch , New Zeal and . All patients received a feedback/education session before r and omization to either four sessions of MET , four sessions of NDRL , or NFC . Outcome data on 122 subjects ( 57.4 % men ) were obtained 6 months following the end of treatment , by an interviewer who was blind to the treatment condition . The primary drinking outcome was unequivocal heavy drinking , defined as drinking 10 or more st and ard drinks six or more times in the follow-up period . Global assessment scale ( GAS ) measured general personal/social functioning . RESULTS Of patients treated with MET , 42.9 % showed unequivocal heavy drinking compared with 62.5 % of the NDRL and 65.0 % of the NFC groups ( p = .04 ) . No significant differences were found for GAS score according to treatment condition . CONCLUSIONS In patients with mild to moderate alcohol dependence , MET is more effective for reducing unequivocal heavy drinking than either a feedback/education session alone or four sessions of NDRL . MET can be considered an effective " value added " counseling intervention in a real-life clinical setting . In patients with mild to moderate alcohol dependence , nondirective reflective listening provides no additional advantage over a feedback/education session alone BACKGROUND Patient involvement in the decision-making process is a key element for good clinical practice . Few data are available on patient involvement in psychiatry . AIMS To assess in a psychiatric out-patient context how psychiatrists involve patients in therapeutic decisions and to determine the extent to which patient and psychiatrist characteristics contribute to patient involvement . METHOD Eighty transcripts from audiotaped first out-patient consultations , conducted by 16 psychiatrists , were rated with the OPTION ( observing patient involvement ) scale . Interrater reliability indices were obtained for 30 r and omly selected interviews . Associations between OPTION scores and some clinical and socio-demographic variables were tested using t-test , ANOVA and Pearson 's correlation coefficient where appropriate . The distribution of scores for each psychiatrist was assessed by intracluster correlation coefficients . RESULTS Interrater reliability and internal consistency of the OPTION scale in the psychiatric setting were satisfactory . The total score and the ratings for the single OPTION items showed a skewed distribution , with a prevalence of scores in the low range of abilities , corresponding to minimal attempts to involve patients or a minimal skill level . CONCLUSIONS The OPTION scale proves to be a reliable instrument to assess patient involvement in a psychiatric setting . Psychiatrists showed poor patient involvement abilities parallel to previous findings in psychiatry and primary care . They need to be encouraged to share treatment decisions with their patients and to apply patient involvement skills . Further research is needed to establish which patient variables and clinical setting s in psychiatry are more amenable to shared decisions , and how participation of psychiatric patients in treatment decisions will affect the outcome This study evaluated the efficacy of as-needed use of the opioid system modulator nalmefene in reducing alcohol consumption in patients with alcohol dependence . Seven hundred and eighteen patients ( placebo=360 ; nalmefene=358 ) , ≥ 18 years of age , with a diagnosis of alcohol dependence , ≥ 6 heavy drinking days and an average alcohol consumption ≥ WHO medium drinking risk level in the 4 weeks preceding screening , were r and omised ( 1:1 ) to 24 weeks of as-needed placebo or nalmefene 18 mg/day . The co- primary efficacy analyses showed a significantly superior effect of nalmefene compared to placebo in the change from baseline to month 6 in heavy drinking days ( group difference : -1.7 days/month [ 95 % CI -3.1 ; -0.4 ] ; p=0.012 ) and a better but not significant effect in reducing total alcohol consumption ( group difference : -5.0 g/day last month [ 95 % CI -10.6 ; 0.7 ] ; p=0.088 ) . A subgroup analysis showed that patients who did not reduce their drinking prior to r and omisation benefitted more from nalmefene . Improvements in Clinical Global Impression and reductions in liver enzymes were greater in the nalmefene group than in the placebo group . Adverse events were more common with nalmefene ; the incidence of adverse events leading to dropout was similar in both groups . This study provides evidence for the efficacy of nalmefene , which constitutes a new pharmacological treatment paradigm in terms of treatment goal ( reduced drinking ) and dosing regimen ( as-needed ) , in alcohol dependent patients unable to reduce alcohol consumption on their own The relationship between individuals ' choice of abstinence or moderate drinking during outpatient behavioral management treatment and outcome over 12 months ' posttreatment was examined . At the initial assessment , 46 % of 106 chronic alcoholic subjects chose abstinence , 44 % chose moderate drinking , and 9 % were unsure . Over the course of treatment , subjects were more likely to move from moderation to abstinence goals , and after the first 4 weeks of treatment , two-thirds chose abstinence . These subjects were older , had more severe alcohol problems ( i.e. , higher MAST scores ) , and were more likely to maintain their weekly alcohol consumption goals during the 16-week treatment period . Moreover , these subjects reported less alcohol use in the 12 month follow-up period , and a greater proportion were judged as having successful outcomes . The implication s of these findings are discussed BACKGROUND Heavy drinking is one of the leading causes of morbidity and mortality in young men . Brief motivational intervention ( BMI ) has shown promising results for young people , but has never been tested in young men in the community who volunteered to receive an intervention . METHODS We evaluated the effectiveness of BMI in reducing alcohol use among heavy episodic users and in maintaining low-risk drinking among nonheavy episodic users . Participants were French-speaking young men attending the m and atory Swiss army conscription process . They were offered the opportunity to receive a 20-minute BMI , and those interested were r and omized into an intervention group ( BMI immediately ) or into a control group ( BMI after the 6-month follow-up assessment , in a waiting list design ) . Analyses were conducted separately for heavy and nonheavy episodic users ( separated using baseline heavy episodic use frequency ) as the hypotheses tested were different between both groups ( primary vs. secondary prevention intervention ) . RESULTS From a pool of 6,085 young men invited to receive BMI , 727 ( 11.9 % ) showed up and 572 were included in the study ( after exclusions related to organizational aspects of the conscription process ) . Among nonheavy episodic users , there was a protective effect of BMI on weekly alcohol use ( p < 0.05 ) . Among heavy episodic users , there were no significant effects of BMI . CONCLUSIONS About 12 % of young men were interested in addressing their drinking within the BMI framework , suggesting that there is some need for easily accessible alcohol intervention . The present intervention did have a preventive effect among low-risk young drinkers in helping them maintain their patterns of alcohol use . An explanation for the lack of effectiveness among heavy episodic users might be that those individuals interested in BMI had patterns of more severe alcohol use , thereby making change more difficult Background Russia has particularly low life expectancy for an industrialised country , with mortality at working ages having fluctuated dramatically over the past few decades , particularly among men . Alcohol has been identified as the most likely cause of these temporal variations . One approach to reducing the alcohol problem in Russia is ' brief interventions ' which seek to change views of the personal acceptability of excessive drinking and to encourage self-directed behaviour change . Very few studies to evaluate the efficacy of brief interventions in Russia have been conducted . Motivational Interviewing ( MI ) is a person-centred counselling style which can be adapted to brief interventions in which help is offered in thinking through behaviour in the context of values and goals , to decide whether change is needed , and if so , how it may best be achieved . Methods This paper reports on an individually r and omised two-armed parallel group exploratory trial . The primary hypothesis is that a brief adaptation of MI will be effective in reducing self-reported hazardous and harmful drinking at 3 months . Participants were drawn from the Izhevsk Family Study II , with eligibility determined based on proxy reports of hazardous and harmful drinking in the past year . All participants underwent a health check , with MI subsequently delivered to those in the intervention arm . Signed consent was obtained from those in the intervention arm only at this point . Both groups were then invited for 3 and 12 month follow ups . The control group did not receive any additional intervention . Results 441 men were r and omised . Of these 61 did not have a health check leaving 190 in each trial arm . Follow up at 3 months was high ( 97 % of those having a health check ) , and very similar in the two trial arms ( 183 in the intervention and 187 in the control).No significant differences were detected between the r and omised groups in either the primary or the secondary outcomes at three months in the intention to treat analyses . The unadjusted odds ratio ( 95 % CI ) for the effect of MI on hazardous and harmful drinking was 0.77 ( 0.51 , 1.16 ) . An adjusted odds ratio of 0.52 ( 0.28 , 0.94 ) was obtained in the pre-specified per protocol analysis . Conclusions This trial demonstrates that it is possible to engage Russian men who drink hazardously in a brief intervention aim ed at reducing alcohol related harm . However the results with respect to the efficacy are equivocal and further , larger-scale trials are warranted . Trial Registration IS RCT N : IS RCT STUDY OBJECTIVE To determine the efficacy of emergency practitioner-performed brief intervention for hazardous/harmful drinkers in reducing alcohol consumption and negative consequences in an emergency department ( ED ) setting . METHODS A r and omized clinical trial ( Project ED Health ) was conducted in an urban ED from May 2002 to November 2003 for hazardous/harmful drinkers . Patients 18 years or older who screened above National Institute for Alcohol Abuse and Alcoholism guidelines for " low-risk " drinking or presented with an injury in the setting of alcohol ingestion were eligible . The mean number of drinks per week and binge-drinking episodes during the past 30 days were collected at 6 and 12 months ; negative consequences and use of treatment services , at 12 months . A Brief Negotiation Interview performed by emergency practitioners was compared to scripted Discharge Instructions . RESULTS A total of 494 hazardous/harmful drinkers were studied . The 2 groups were similar with respect to baseline characteristics . In the Brief Negotiation Interview group , the mean number of drinks per week at 12 months was 3.8 less than the 13.6 reported at baseline . The Discharge Instructions group decreased 2.6 from 12.4 at baseline . Likewise , binge-drinking episodes per month decreased by 2.0 from a baseline of 6.0 in the Brief Negotiation Interview group and 1.5 from 5.4 in the Discharge Instructions group . For each outcome , the time effect was significant and the treatment effect was not . CONCLUSION Among ED patients with hazardous/harmful drinking , we did not detect a difference in efficacy between emergency practitioner-performed Brief Negotiation Interview and Discharge Instructions . Further studies to test the efficacy of brief intervention in the ED are needed The aim of this research was to evaluate the effectiveness of long-term brief intervention in routine general practice . In five primary care out-patient clinics in a Finnish town , 296 male early-phase heavy drinkers consulting a general practitioner ( GP ) for various reasons were identified . Control group C ( n = 88 ) was informed of the risks of drinking after the screening and were advised at the subsequent feedback about 2 weeks later to reduce their drinking . Groups A ( n = 109 ) and B ( n = 99 ) were offered in addition seven and three brief intervention sessions , respectively . All GPs took part , whether or not they indicated a special interest . The main outcome measures were differences between beginning and end-point at 3 years in self-reported alcohol consumption , mean corpuscular volume ( MCV ) , and serum carbohydrate-deficient transferrin , aspartate aminotransferase , alanine aminotransferase and gamma-glutamyltransferase . There were no statistically significant differences between study groups A , B and C in mean changes in outcome measures . Within all the groups , MCV decreased . Depending on the outcome measure used and the study group analysed , clinical ly significant reduction of drinking was found in 25 - 53 % of the subjects . In routine general practice , giving additional sessions of brief intervention may not be as effective as in special research conditions . Factors reducing the effectiveness of brief intervention programmes should be investigated , so that primary health care staff can be better supported in their efforts The authors evaluated the efficacy of Brief Alcohol Screening and Intervention for College Students ( BASICS - L. A. Dimeff , J. S. Baer , D. R. Kivlahan , & G. A. Marlatt , 1999 ) , a single session of drinking-related feedback intended to reduce heavy drinking and related harm . College student drinkers ( N = 99 ) were assigned to BASICS , an educational intervention , or an assessment -only control group . At 3 months postintervention . there were no overall significant group differences , but heavier drinking BASICS participants showed greater reductions in weekly alcohol consumption and binge drinking than did heavier drinking control and education participants . At 9 months , heavier drinking BASICS participants again showed the largest effect sizes . BASICS participants evaluated the intervention more favorably than did education participants . This study suggests that BASICS may be more efficacious than educational interventions for heavier drinking college students AIMS To test if a brief motivational intervention ( BMI ) in a non-treatment seeking population of heavy drinkers results in a reduced alcohol intake . METHODS Screening of 12,364 participants in a Danish health examination survey led to 1026 heavy drinkers of whom 772 were included and r and omized to a BMI group ( n = 391 ) or a control group ( n = 381 ) receiving two leaflets about alcohol . Follow-up took place after 6 and 12 months including 670 and 616 participants respectively . The outcome measure was self-reported weekly alcohol consumption . Data were analysed according to the intention-to-treat principle . We used the Motivational Interviewing Treatment Integrity 3.0 code ( MITI ) as a quality control of the interventions delivered . RESULTS The intervention effect of the BMI was -1.0 drinks/week , but the effect was not significant . The MITI analysis showed that the quality of the BMI delivered was sub-optimal , as only one of four aspects was above the recommended level for beginning proficiency . CONCLUSION We found no effect of a BMI in reducing alcohol consumption . The generalizability of the study is question able , as individuals with the lowest level of education , low income and unmarried individuals are under-represented AIMS To evaluate the effectiveness of brief alcohol intervention ( BAI ) in reducing alcohol use among hazardous drinkers treated in the emergency department ( ED ) after an injury ; in addition it tests whether assessment of alcohol use without BAI is sufficient to reduce hazardous drinking . DESIGN R and omized controlled clinical trial with 12-month follow-up conducted between January 2003 and June 2005 . SETTING Urban academic emergency department ( ED ) of the Lausanne University Hospital , Lausanne , Switzerl and . PARTICIPANTS A total of 5136 consecutive patients attending ED after an injury completed a seven-item general and a three-item alcohol screen and 1472 ( 28.7 % ) were positive for hazardous drinking according to the National Institute on Alcohol Abuse and Addiction definition ; of these 987 ( 67.1 % ) were r and omized into a BAI group ( n = 310 ) or a control group with screening and assessment ( n = 342 ) or a control group with screening only ( n = 335 ) and then a total of 770 patients ( 78.0 % ) completed the 12-month follow-up procedures . INTERVENTION A single 10 - 15-minute session of st and ardized BAI conducted by a trained research assistant . MEASUREMENTS Percentage of participants who have changed to low-risk drinking at follow-up . FINDINGS Data obtained at 12 months indicated that similar proportions were low-risk drinkers in BAI versus control groups with and without assessment ( 35.6 % , 34.0 % , 37.0 % , respectively , P = 0.71 ) . Data also indicated similar reductions in drinking frequency , quantity , binge drinking frequency and Alcohol Use Disorders Identification Test ( AUDIT ) scores across groups . All groups reported similar numbers of days hospitalized and numbers of medical consults in the last 12 months . A model including age groups , gender , AUDIT and injury severity scores indicated that BAI had no influence on the main alcohol use outcome . CONCLUSIONS This study provides the evidence that a 10 - 15-minute BAI does not decrease alcohol use and health re source utilization in hazardous drinkers treated in the ED , and demonstrates that commonly found decreases in hazardous alcohol use in control groups can not be attributed to the baseline alcohol assessment This is a r and omized controlled trial of 511 eligible women treated for diabetes , hypertension , infertility , or osteoporosis on an outpatient basis to test the hypothesis that those r and omized to a brief intervention ( BI ) will drink less than those in the control condition 12 months later . A secondary goal was to identify the characteristics associated with changes in drinking outcome . All 511 completed the initial alcohol assessment , and 96 % completed the 12-month follow-up interview . Those receiving the BI also had 3- and 6-month interviews . Four outcomes were assessed : ( a ) mean drinks per drinking day , ( b ) percent drinking days , ( c ) binge episodes defined as four or more drinks per occasion , and ( d ) weeks of drinking exceeding the National Institute on Alcohol Abuse and Alcoholism sensible drinking limits . Overall , there were no differences in drinking outcome by treatment group . Characteristics associated with changes in drinking , however , were identified to provide possible direction for future investigation STUDY OBJECTIVE This study tests the effect of a brief intervention with emergency department ( ED ) patients to reduce at-risk drinking . METHODS We enrolled patients aged 18 years or older who screened positive for at-risk drinking in an urban academic ED and used alternative allocation to assign them to control or intervention status . A 20-minute , semiscripted , negotiated interview was conducted with the intervention group in English and Spanish by 3 health promotion advocates ( peer educators ) . The Alcohol Use Identification Test ( AUDIT ) was administered at baseline and 3 months after enrollment . RESULTS Among 1,036 patients screened for at-risk drinking , 295 with CAGE question naire score greater than 1 and no alcohol treatment in the past year enrolled in the study and were r and omly assigned to the control arm ( n=151 ) or the intervention arm ( n=144 ) . Follow-up was achieved with 88 patients in the intervention group and 97 patients in the control group ( 63 % of enrollees ) . Among the 185 patients followed up , 64 % of the intervention group versus 80 % of the control group scored greater than 7 on the follow-up AUDIT ( scored on a scale of 1 to 40 ; P<.05 , odds ratio [ OR ] 2.35 , 95 % confidence interval [ CI ] 1.21 to 4.55 ) . Multinomial logistic regression analysis demonstrates , after controlling for demographic characteristics and other independent variables , that assignment to intervention status decreased the odds of at-risk ( moderate ) drinking as defined by AUDIT scores of 7 to 18 ( OR 0.42 , P<.05 , 95 % CI 0.19 to 0.91 ) but did not affect patients with AUDIT scores in the 19 to 40 range . CONCLUSION Brief motivational intervention administered by peer educators to ED patients appears to reduce moderately risky drinking and associated problems BACKGROUND Alcohol screening , brief intervention , and referral to specialized treatment ( ASBIR ) reduce drinking and related harms . Unanswered questions are how to manage nondependent patients with poor response to brief interventions , how to manage dependent patients who do not obtain treatment , and how to ensure population -wide delivery of ASBIR . Telephone-administered counseling may provide answers . METHODS We conducted a 12-month r and omized controlled trial of a telephone and mail intervention for non-treatment-seeking primary care patients with alcohol use disorders . We enrolled 897 subjects after systematic screening in 18 primary care clinic waiting rooms in and around Madison and Milwaukee , Wisconsin , and subsequent telephone-administered diagnostic interviews . Experimental subjects received up to six sessions of protocol -driven telephone counseling based on principles of motivational interviewing and stages of readiness to change . Control subjects received a pamphlet on healthy lifestyles . The paper reports on 3-month drinking outcomes for men and women with alcohol abuse and dependence . RESULTS Male experimental subjects ( N=199 ) manifested a 30.6 % decline in risky drinking days , compared with a 8.3 % decline in controls ( N=201 , p<0.001 ) . The total consumption declined by 17.3 % compared with 12.9 % by controls ( p=0.001 ) . Female experimental subjects ( N=246 ) manifested a 17.2 % decrease in risky drinking days compared with an 11.5 % decrease by controls ( N=251 ; p = NS ) and a 13.9 % decline in total consumption compared with 11.0 % by controls ( p = NS ) . Greater numbers of telephone counseling sessions were associated with greater declines in drinking . CONCLUSION Following systematic screening , a six-session telephone and mail intervention is more effective than a pamphlet in reducing drinking at 3 months for non-treatment-seeking men with alcohol abuse and dependence . An intervention effect of the enrollment procedures may have obscured further intervention effectiveness . Telephone counseling shows promise for non-treatment-seeking primary care patients with alcohol use disorders BACKGROUND Clinical studies with opioid antagonists for treatment of problem drinking have mainly been conducted in specialized alcohol treatment centers , included structured psychosocial treatment , and have focused on maintaining abstinence after a period of abstinence from alcohol . METHODS This multisite , r and omized double-blind study investigated targeted nalmefene in reducing heavy drinking . Specialized alcohol treatment centers and private general practice s enrolled 403 subjects ( 328 men , 75 women ) . Subjects were instructed to take nalmefene 10 to 40 mg ( n=242 ) or placebo ( n=161 ) when they believed drinking to be imminent . After 28 weeks , 57 subjects from the nalmefene group continued into a 24-week r and omized withdrawal extension . Concomitant psychosocial intervention was minimal and no treatment goals were imposed . Alcohol consumption was recorded using the time-line follow-back method . Biochemical indicators of alcohol use were also measured . RESULTS The mean monthly number of heavy drinking days ( HDDs ) during the 12-week period before inclusion was 15.5 ( SD 6.9 ) in the nalmefene group and 16.2 ( SD 6.9 ) in the placebo group . During treatment , the mean numbers of HDDs were 8.6 to 9.3 in the nalmefene group and 10.6 to 12.0 in the placebo group ( p=0.0065 ) . The levels of serum alanine aminotransferase and gamma-glutamyl transferase decreased in the nalmefene group compared with the placebo group ( p=0.0088 and 0.0023 ) . During the r and omized withdrawal period , subjects r and omized to placebo apparently returned to heavier drinking . Subjects receiving nalmefene reported more nausea , insomnia , fatigue , dizziness , and malaise than subjects on placebo . CONCLUSIONS Nalmefene appears to be effective and safe in reducing heavy drinking , even when accompanied by minimal psychosocial support AIMS To test the effectiveness of a brief psychological intervention for problem drinking among out patients in a hospital setting . METHODS Over a period of 3 years physicians screened patients who visited an outpatient clinic for general internal medicine for problem drinking . Of the 4728 patients screened , 284 ( 6 % ) scored positive on problem drinking of whom 123 participated in the study . They received a computerized baseline assessment and were r and omly allocated to a brief psychosocial intervention given by a psychologist ( Dutch version of W. R. Millers ' Drinker 's Check-Up ) ( n = 61 ) or to ' care as usual ' ( n = 62 ) . They were followed up at 6 months . The outcome measures were alcohol consumption and the increase in motivation to reduce alcohol consumption . RESULTS Most patients reduced their alcohol consumption over time , but no differences were found between the intervention and control groups . A slightly , but not significantly , larger proportion of patients who received the intervention increased their motivation to change . CONCLUSIONS No conclusive evidence was found for the effectiveness of adding a brief psychological intervention to the physician 's advice for problem drinking among out patients in a hospital setting AIMS To determine the effectiveness of Motivational Enhancement Therapy ( MET ) for hazardous drinkers in Primary Care Unit ( PCU ) setting s in rural Thail and . METHODS A r and omized controlled trial was conducted in eight PCUs in Ubonratchatanee and Chachoengsao provinces in Thail and . Hazardous drinkers were identified using the World Health Organization-recommended Alcohol Use Disorder Identification Test . Of 117 eligible participants ( 91 % male ) , 59 were r and omized to the intervention group to receive MET in three individual appointments with a trained nurse and 58 to an assessment -only control group . Outcome evaluations were carried out after 6 weeks , 3 months and 6 months . RESULTS Follow-up data were available on 84 , 94 and 91 % of subjects , respectively , at the three intervals . Self-reported drinks per drinking day , frequency of hazardous drinking assessed either on a daily or weekly basis , and of binge drinking sessions were reduced in the intervention group more than in the control group ( P < 0.05 ) after both 3 and 6 months . The groups did not generally differ at 6 weeks . However , although self-reported consumption in both groups fell from baseline to 6-month follow-up , serum gamma-glutamyl transferase increased in both groups , which raises doubts about the validity of this marker in this sample and /or the validity of the self-reported data in this study . CONCLUSION MET delivered by nurses in PCUs in Thail and appears to be an effective intervention for male hazardous drinkers . Uncertainties about the validity of self-reported data jeopardize the safety of this conclusion OBJECTIVE This study evaluated the relative efficacy of personalized drinking feedback ( PDF ) delivered with and without a motivational interview ( MI ) for college student drinkers . METHOD Heavy-drinking college students ( N = 54 ; 691 % female ) were identified from a large screening sample and r and omly assigned either to receive PDF during a single MI session or to receive PDF without an MI . Of these participants , 51 ( 94 % ) completed a 6-month follow-up assessment that included measures of alcohol consumption and alcohol-related problems . RESULTS At 6-months postintervention , participants in both groups showed significant , small to moderate reductions in alcohol consumption , but the groups did not differ . Women showed larger reductions than men . Rates of alcohol-related problems remained relatively unchanged . CONCLUSIONS The hypothesis that an MI would enhance the efficacy of PDF was not supported AIMS ( 1 ) To assess the benefits of matching alcohol dependent clients to three treatments , based upon a priori hypotheses involving 11 client attributes ; ( 2 ) to discuss the implication s of these findings and of matching hypotheses previously reported from Project MATCH . SETTING AND PARTICIPANTS ( 1 ) Clients receiving outpatient therapy ( N = 952 ; 72 % male ) ; ( 2 ) clients receiving aftercare therapy following inpatient or day hospital treatment ( N = 774 ; 80 % male ) . INTERVENTION Clients were r and omly assigned to one of three 12-week , manual-guided , individual treatments : Cognitive Behavioral Coping Skills Therapy ( CBT ) , Motivational Enhancement Therapy ( MET ) or Twelve-Step Facilitation Therapy ( TSF ) . DESIGN Two parallel but independent r and omized clinical trials were conducted , one with out patients , one with aftercare clients . Participants were monitored over 15 months including a 1-year post-treatment period . Individual differences in response to treatment were modeled as a latent growth process and evaluated for 17 contrasts specified a priori . Outcome measures were percentage of days abstinent and drinks per drinking day . FINDINGS Two a priori contrasts demonstrated significant post-treatment attribute by treatment interactions : ( 1 ) out patients high in anger and treated in MET had better post-treatment drinking than in CBT ; ( 2 ) aftercare clients high in alcohol dependence had better post-treatment outcomes in TSF ; low dependence clients did better in CBT . Other matching effects varied over time , while still other interactions were opposite that predicted . CONCLUSIONS ( 1 ) Anger and dependence should be considered when assigning clients to these three treatments ; ( 2 ) considered together with the results of the primary hypotheses , matching effects contrasting these psychotherapies are not robust . Possible explanations include : ( a ) among the client variables and treatments tested , matching may not be an important factor in determining client outcomes ; ( b ) design issues limited the robustness of effects ; and ( c ) a more fully specified theory of matching is necessary to account for the complexity of the results This study evaluated the long-term efficacy and safety of nalmefene treatment in reducing alcohol consumption . We r and omised ( 1:3 ) 675 alcohol-dependent patients ≥ 18 years of age to 52 weeks of as-needed treatment with placebo or nalmefene 18 mg/day : A total of 112 patients ( 68 % ) in the placebo group and 310 ( 62 % ) in the nalmefene group completed the study . At month 6 , the co- primary outcome variables showed no statistically-significant differences between the treatment groups ; but at month 13 , nalmefene was more effective than placebo , both in the reduction of the number of heavy drinking days ( HDDs ) ( − 1.6 days/month ( 95 % CI − 2.9 ; − 0.3 ) ; p = 0.017 ) and the reduction of total alcohol consumption ( TAC ) ( − 6.5 g/day last month ( 95 % CI − 12.5 ; − 0.4 ) ; p = 0.036 ) . In a subgroup analysis of patients with high/very high drinking risk levels at screening and at r and omisation ( the target population ) , there was a significant effect in favour of nalmefene on TAC at month 6 , and on both HDD and TAC at month 13 . Improvements in Clinical Global Impression and liver enzymes were greater with nalmefene , compared to placebo . Most adverse events were mild or moderate , and transient ; adverse events , including those leading to dropout , were more common with nalmefene . This study provides evidence for the long-term safety and efficacy of nalmefene as-needed in alcohol-dependent patients whom continue to drink heavily , following a brief intervention AIMS To examine the effectiveness of a brief intervention ( BI ) and cognitive behaviour therapy ( CBT ) for alcohol abuse . DESIGN A r and omized trial with clients r and omized within counsellors . SETTING Community-based drug and alcohol counselling in Australia . PARTICIPANTS Of all new clients attending counselling . 869 ( 82 % ) completed a computerized assessment at their first consultation . Four hundred and twenty-one ( 48 % ) were defined as eligible , of whom 295 ( 70 % ) consented and were allocated r and omly to an intervention . Of these , 13 3 ( 45 % ) were followed-up at 6 months post-test . INTERVENTIONS BI comprised the elements identified by the acronym FRAMES : feedback , responsibility , advice , menu , empathy , self-efficacy . Face-to-face counselling time was not to exceed 90 minutes . CBT comprised six consecutive weekly sessions : introduction : cravings and urges ; managing crises ; saying ' no ' and solving problems : emergencies and lapses : and maintenance . Total face-to-face counselling time was 270 minutes ( six 45-minute sessions ) . MEASUREMENTS Treatment outcomes are measured in terms of counsellor compliance , client satisfaction , weekly and binge consumption , alcohol-related problems , the AUDIT question naire and cost-effectiveness . FINDINGS When analysed on an intention-to-treat basis and for those followed-up . treatment outcomes between BI and CBT were not statistically significantly different at pre- or post-test , whether considered as continuous or categorical variables . BI was statistically significantly more cost-effective than CBT and there was no difference between them in clients ' reported levels of satisfaction . CONCLUSION For low-dependence alcohol abuse in community setting s , BI may be the treatment of choice BACKGROUND A r and omized controlled trial of screening , brief intervention , and referral to treatment ( SBIRT ) among at-risk ( based on average number of drinks per week and drinks per drinking day ) and dependent drinkers was conducted in an emergency department ( ED ) among 446 patients 18 and older in Sosnowiec , Pol and . METHODS Patients were recruited over a 23-week period ( 4:00 pm to 12:00 midnight ) and r and omized to 1 of 3 conditions : screened-only ( n = 147 ) , assessed ( n = 152 ) , and intervention ( n = 147 ) . Patients in the assessed and intervention conditions were blindly reassessed via a telephone interview at 3 months , and all 3 groups were assessed at 12 months ( screened-only = 92 , assessed = 99 , and intervention = 87 ) . RESULTS No difference was found across the 3 conditions in at-risk drinking at 12 months , as the primary outcome variable , or in decrease in the number of drinks per drinking day , with all 3 groups showing a significant reduction in both . Significant declines between baseline and 12 months in secondary outcomes of the RAPS4 , number of drinking days per week , and the maximum number of drinks on an occasion were seen only for the intervention condition , and in negative consequences for both the assessment and intervention conditions . CONCLUSIONS Data suggest that improvements in drinking outcomes found in the assessment condition were not because of assessment reactivity , with both the screened and intervention conditions demonstrating greater ( although nonsignificant ) improvement than the assessed condition . Only those in the intervention condition showed significant improvement in all outcome variables from baseline to 12-month follow-up . Although group by time interaction effects were not found to be significant , these findings suggest that declines in drinking measures for those receiving a brief intervention can be maintained at long-term follow-up OBJECTIVE The study aim was to test whether a brief motivational intervention , with or without a booster session , would improve drinking-related outcomes more than st and ard Emergency Department ( ED ) treatment . METHOD The study population consisted of 539 ( 78 % male ) injured patients treated in the ED and discharged to the community following their treatment . Injured patients met inclusion criteria if they were assessed as hazardous or harmful drinkers by scoring eight or more on the AUDIT and /or having alcohol in their system at the time of their injury or ED visit . Patients were r and omly assigned to either st and ard care ( SC ) , brief intervention ( BI ) or brief intervention plus a booster session ( BIB ) . At 1-year follow-up , 447 patients ( 83 % of the sample ) were re-interviewed to measure alcohol-related negative consequences , injuries and drinking . RESULTS Patients receiving BIB , but not B1 patients , reduced alcohol-related negative consequences and alcohol-related injuries more than did those in the SC group . All three groups reduced their days of heavy drinking . Patients with histories of hazardous drinking responded to BIB , whether or not they had consumed alcohol prior to their injury . CONCLUSIONS Together , these results indicate that the effects of a booster session that is added to a brief intervention in the ED can be helpful to injured patients with a history of hazardous or harmful drinking , irrespective of whether they have consumed alcohol prior to their injury INTRODUCTION The study was design ed to test a brief intervention for reducing alcohol consumption among moderate to heavy ( hazardous ) drinkers in a busy HMO primary care setting . METHODS In a r and omized controlled trial , hazardous drinkers ( n = 516 ) were identified by the AUDIT screening question naire . Intervention included brief clinician advice ( 30 seconds ) , a 15-minute motivational session by counselors , and printed material s. RESULTS At six-month follow-up , intervention subjects reported fewer total st and ard drinks in the past three months ( 176 versus 216 , P = .04 , one-tailed ) and fewer drinking days per week ( 2.8 versus 3.3 , P = .02 ) than controls , but similar drinks per drinking day ( 3.3 versus 3.5 ; P = .13 ) . At 12 months , intervention subjects again reported fewer drinking days per week ( 2.7 versus 3.1 ; P = .04 ) than controls , but similar numbers of st and ard drinks ( 157 versus 179 ; P = .13 ) and drinks per drinking day ( 3.6 versus 3.3 ; P = .20 ) . Intervention subjects were somewhat more likely than controls to report drinking within daily recommended limits ( < or = 3 for men , < or = 2 for women ) at both six months ( 79 % versus 71 % ; P = .06 ) and 12 months ( 80 % versus 73 % ; P = .07 ) , but did not differ significantly from controls on other drinking outcomes ( percent abstinent , frequency of drinking > or = 6 drinks per drinking occasion , estimated peak blood alcohol concentration ) , or use of medical care in the year following intervention . CONCLUSIONS A one-time , brief motivational intervention using minimal clinician time supplemented by trained counselors result ed in a modest reduction in frequency of alcohol consumption in a busy primary care population . Future research should focus on strengthening and maintaining intervention effects A pooled analysis of ‘ as-needed medication use ' data from 1,276 patients in two r and omised , double-blind , placebo-controlled , parallel-group trials of nalmefene in the treatment of alcohol dependence was performed to explore whether an ‘ as-needed ' regimen is an acceptable and feasible strategy in patients seeking help for alcohol dependence . Adherence was defined as alcohol consumption and medication intake , or no alcohol consumption ( with or without medication intake ) . Nalmefene was taken on approximately half of the study days ; placebo was taken more often than nalmefene ( 52.8 vs. 64.5 % of days , respectively ) . In each treatment group medication intake appeared to vary according to patients ' needs in that intake correlated with the baseline drinking pattern . Sixty-eight percent of the nalmefene-treated patients ( 78 % of the study completers ) adhered to the as-needed treatment regimen on at least 80 % of the study days . In conclusion , as-needed use is a feasible , patient-centred approach that engages patients with alcohol dependence in the active management of their illness AIMS Recommendations for routine alcohol screening and brief counselling intervention in primary health care rest on results from intervention efficacy studies . By conducting a pragmatic controlled trial ( PCT ) , we aim ed at evaluating the effectiveness of the WHO recommendations for screening and brief intervention ( SBI ) in general practice . METHODS A r and omized PCT ( brief counselling intervention vs no intervention ) involving 39 Danish general practitioners ( GPs ) . Systematic screening of 6897 adults led to inclusion of 906 risky drinkers , and research follow-up on 537 of these after 12 - 14 months . Outcome measures focused on patients ' acceptance of screening and intervention and their self-reported alcohol consumption . RESULTS Patient acceptance of screening and intervention -10.3 % ( N = 794 ) of the target population ( N = 7 , 691 ) explicitly refused screening . All intervention group subjects ( N = 442 ) were exposed to an instant brief counselling session while only 17.9 % of them ( 79/442 ) attended a follow-up consultation that was offered by their GP . Consumption Changes At one-year follow-up , average weekly consumption had increased by 0.7 drinks in both comparison groups . As secondary findings , we observed an indiscriminate absolute risk reduction ( ARR = 0.08 ( 95 % CI : -0.02 ; 0.18 ) ) in male binge drinking , but adverse intervention effects for women on the secondary outcomes ( binge drinking ARR = -0.30 ( 95 % CI : -0.47 ; -0.09 ) ) . CONCLUSIONS The results of brief interventions in everyday general practice performed on the basis of systematic question naire screening may fall short of theoretical expectations . When applied to non-selected groups in everyday general practice SBI may have little effect and engender diverse outcome . Women may be more susceptible to defensive reactions than men 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 OBJECTIVE Brief interventions for hazardous and low-dependent drinkers in the primary care setting have considerable empirical support . The purpose of this study was to ( 1 ) evaluate the effects of brief advice ( BA ) and motivational enhancement ( ME ) interventions on alcohol consumption . In addition , a hindsight matching design was used to ( 2 ) study the moderator effects of patient readiness to change ( alcohol use ) on alcohol consumption . METHOD The subjects ( N = 301 , 70 % men ) were patients 21 years of age or older who presented for treatment at one of 12 primary care clinics . After screening for eligibility and providing consent to participate in the study , the patients completed a baseline assessment and were r and omly assigned to the BA , ME or st and ard care ( SC ) interventions condition . Follow-up assessment s were completed at 1- , 3- , 6- , 9- and 12-months postbaseline assessment . RESULTS Evaluation of the first hypothesis ( n = 232 for these analyses ) showed that all participants tended to reduce their alcohol use considerably between the baseline and 12-month assessment s. In addition , evaluation of the second hypothesis showed a moderator effect of readiness to change in predicting the number of drinks at 12 months , such that the BA intervention seemed more effective for patients relatively low in readiness to change compared to those higher in readiness . Readiness to change did not seem to be related to changes in drinking of participants in the SC or ME conditions . CONCLUSIONS The results confirm that , among primary care patients , substantial changes in alcohol consumption are possible . They further suggest that matching studies of patient readiness to change their alcohol use , as well as other variables , are warranted BACKGROUND There is a large treatment gap in alcohol dependence , and current treatments are only moderately effective in preventing relapse . New treatment modalities , allowing for reduction of alcohol consumption as a treatment goal are needed . This study evaluated the efficacy of as-needed use of the opioid system modulator nalmefene in reducing alcohol consumption in patients with alcohol dependence . METHODS Six hundred and four patients ( placebo = 298 ; nalmefene = 306),≥18 years of age , with a diagnosis of alcohol dependence,≥6 heavy drinking days , and average alcohol consumption≥World Health Organization medium drinking risk level in the 4 weeks preceding screening , were r and omized ( 1:1 ) to 24 weeks of as-needed placebo or nalmefene 18 mg . RESULTS Patients taking placebo ( n = 289 ) and patients taking nalmefene ( n = 290 ) were included in the efficacy analyses . At Month 6 , there was a significant effect of nalmefene compared with placebo in reducing the number of heavy drinking days ( -2.3 days [ 95 % confidence interval:-3.8 to-.8 ] ; p = .0021 ) and total alcohol consumption ( -11.0 g/day [ 95 % confidence interval:-16.8 to-5.1 ] ; p = .0003 ) . Improvements in Clinical Global Impression and liver enzymes were larger in the nalmefene group compared with placebo at Week 24 . Adverse events ( most mild or moderate ) and dropouts due to adverse events were more common with nalmefene than placebo . The number of patients with serious adverse events was similar in the two groups . CONCLUSIONS Nalmefene provides clinical benefit , constitutes a potential new pharmacological treatment paradigm in terms of the treatment goal and dosing regimen , and provides a method to address the unmet medical need in patients with alcohol dependence that need to reduce their alcohol consumption STUDY OBJECTIVE Brief interventions have been shown to reduce alcohol use and improve outcomes in hazardous and harmful drinkers , but evidence to support their use in emergency department ( ED ) patients is limited . The use of research assessment s in studies of brief interventions may contribute to uncertainty about their effectiveness . Therefore we seek to determine ( 1 ) if an emergency practitioner-performed Brief Negotiation Interview or a Brief Negotiation Interview with a booster reduces alcohol consumption compared with st and ard care ; and ( 2 ) the impact of research assessment s on drinking outcomes using a st and ard care-no- assessment group . METHODS We r and omized 889 adult ED patients with hazardous and harmful drinking . A total of 740 received an emergency practitioner-performed Brief Negotiation Interview ( n=297 ) , a Brief Negotiation Interview with a 1-month follow-up telephone booster ( Brief Negotiation Interview with booster ) ( n=295 ) , or st and ard care ( n=148 ) . We also included a st and ard care with no assessment s ( n=149 ) group to examine the effect of assessment s on drinking outcomes . Primary outcomes analyzed with mixed-models procedures included past 7-day alcohol consumption and 28-day binge episodes at 6 and 12 months , collected by interactive voice response . Secondary outcomes included negative health behaviors and consequences collected by telephone surveys . RESULTS The reduction in mean number of drinks in the past 7 days from baseline to 6 and 12 months was significantly greater in the Brief Negotiation Interview with booster ( from 20.4 [ 95 % confidence interval { CI } 18.8 to 22.0 ] to 11.6 [ 95 % CI 9.7 to 13.5 ] to 13.0 [ 95 % CI 10.5 to 15.5 ] ) and Brief Negotiation Interview ( from 19.8 [ 95 % CI 18.3 to 21.4 ] to 12.7 [ 95 % CI 10.8 to 14.6 ] to 14.3 [ 95 % CI 11.9 to 16.8 ] ) than in st and ard care ( from 20.9 [ 95 % CI 18.7 to 23.2 ] to 14.2 [ 95 % CI 11.2 to 17.1 ] to 17.6 [ 95 % CI 14.1 to 21.2 ] ) . The reduction in 28-day binge episodes was also greater in the Brief Negotiation Interview with booster ( from 7.5 [ 95 % CI 6.8 to 8.2 ] to 4.4 [ 95 % CI 3.6 to 5.2 ] to 4.7 [ 95 % CI 3.9 to 5.6 ] ) and Brief Negotiation Interview ( from 7.2 [ 95 % CI 6.5 to 7.9 ] to 4.8 [ 95 % CI 4.0 to 5.6 ] to 5.1 [ 95 % CI 4.2 to 5.9 ] ) than in st and ard care ( from 7.2 [ 95 % CI 6.2 to 8.2 ] to 5.7 [ 95 % CI 4.5 to 6.9 ] to 5.8 [ 95 % CI 4.6 to 7.0 ] ) . The Brief Negotiation Interview with booster offered no significant benefit over the Brief Negotiation Interview alone . There were no differences in drinking outcomes between the st and ard care and st and ard care-no assessment groups . The reductions in rates of driving after drinking more than 3 drinks from baseline to 12 months were greater in the Brief Negotiation Interview ( 38 % to 29 % ) and Brief Negotiation Interview with booster ( 39 % to 31 % ) groups than in the st and ard care group ( 43 % to 42 % ) . CONCLUSION Emergency practitioner-performed brief interventions can reduce alcohol consumption and episodes of driving after drinking in hazardous and harmful drinkers . These results support the use of brief interventions in ED setting In this r and omized controlled trial , the authors evaluated brief motivational interventions ( BMI s ) for at-risk college drinkers . Heavy drinking students ( N = 509 ; 65 % women , 35 % men ) were r and omized into 1 of 6 intervention conditions formed by crossing the baseline Timeline Followback ( TLFB ) interview ( present versus absent ) and intervention type ( basic BMI , BMI enhanced with a decisional balance module , or none ) . Assessment s completed at baseline , 1 , 6 , and 12 months measured typical and risky drinking as well as drinking-related problems . Relative to controls , the TLFB interview reduced consumption but not problems at 1 month . The basic BMI improved all drinking outcomes beyond the effects of the TLFB interview at 1 month , whereas the enhanced BMI did not . Risk reduction achieved by brief interventions maintained throughout the follow-up year BACKGROUND Today , heavy drinking is a common health hazard among women . The evidence in favor of providing some kind of brief intervention to reduce drinking is quite convincing . However , we do not know if intervention works in a natural environment of routine health care . The purpose of this study was to evaluate the effectiveness of long-lasting , brief alcohol intervention counseling for women in a routine general practice setting . METHODS In five primary care outpatient clinics in a Finnish town , 118 female early-phase heavy drinkers who consulted their general practitioners for various reasons were given brief alcohol intervention counseling . Intervention groups A ( n = 40 ) and B ( n = 38 ) were offered seven and three brief intervention sessions , respectively , over a 3-yr period . The control group C ( n = 40 ) was advised to reduce drinking at baseline . Main outcome measures were self-reported weekly alcohol consumption , carbohydrate-deficient transferrin , mean corpuscular volume ( MCV ) , aspartate aminotransferase , alanine aminotransferase , and gamma-glutamyltransferase . RESULTS Depending on the outcome measure and the study group , clinical ly meaningful reduction of drinking was found in 27 % to 75 % of the heavy drinkers . Within all the groups , MCV significantly decreased . However , there were no statistically significant differences between study groups A , B , and C in the mean changes between the beginning and endpoint in the main outcome measures . CONCLUSIONS The present study indicated that minimal advice , as offered to group C , was associated with reduced drinking as much as the brief intervention , as offered to groups A and B , given over a 3-yr period . Furthermore , in the routine setting of the general practice office , the effectiveness of the brief intervention may not be as good as in special research conditions . The factors possibly reducing the effectiveness in a routine setting are unknown . Thus , different methods of implementing brief intervention need to be evaluated to find better ways to support general practice personnel in their efforts to help heavy-drinking female patients to reduce their drinking Assessed cognitive-behavioral program with a goal of either abstinence or controlled drinking using 70 early-stage problem drinkers who were r and omly assigned to 1 of 2 goal conditions and within each condition to 1 of 2 therapists . Ss averaged 6 individual weekly sessions , each lasting approximately 90 min . Both groups were taught to identify risk situations and existing competencies , to develop cognitive and behavioral coping , and to assess their progress objective ly . The controlled-drinking group was also taught procedures for moderate drinking . Over the 2-yr follow-up period , no significant differences were found between the groups in reported alcohol consumption . Six months after treatment , drinking had been reduced from an average of about 51 drinks/week to 13 , and this reduction was maintained throughout the 2nd year . Reports of drinking were corroborated by independent measures . Although the outcomes of the groups were similar , controlled drinking was considered to be a more suitable goal ; it was more acceptable to the majority of the clients , and most of those assigned to abstinence developed moderate drinking on their own . ( 51 ref ) ( PsycINFO Data base Record ( c ) 2006 APA , all rights reserved Several studies have shown the opioid antagonist naltrexone to be effective when combined with psychosocial therapies for the treatment of patients who are dependent on alcohol with fixed medication and time ( 12 weeks ) . In this study , 121 nonabstinent out patients with alcohol dependence ( DSM-IV ) were treated with sessions of cognitive coping skills ( N = 67 ) or supportive therapy ( N = 54 ) and either naltrexone 50 mg/day ( N = 63 ) or placebo ( N = 58 ) daily for the first 12 weeks and thereafter for 20 weeks only when craving alcohol ( i.e. , targeted medication ) in a prospect i ve one-center , dual , double-blind , r and omized clinical trial . The dropout rate for all subjects was 16.5 % during the first 12-week period and approximately twice that level by the end of the study . There were no significant group differences in study completion and therapy participation rates . After the continuous medication ( 12 weeks ) , the coping/naltrexone group had the best outcome , and coping/placebo had the worst . This difference remained during the targeted medication period ( the following 20 weeks ) . Naltrexone was not better than placebo in the supportive groups , but it had a significant effect in the coping groups : 27 % of the coping/naltrexone patients had no relapses to heavy drinking throughout the 32 weeks , compared with only 3 % of the coping/placebo patients . The authors ’ data confirm the original finding of the efficacy of naltrexone in conjunction with coping skills therapy . In addition , their data show that detoxification is not required and that targeted medication taken only when craving occurs is effective in maintaining the reduction in heavy drinking BACKGROUND Numerous reports document that preinjury alcohol use is associated with all modes of injury requiring treatment in a trauma center , with 25 % to 50 % or more of patients testing positive for alcohol at the time of admission . There is evidence that in trauma patients unaddressed alcohol use problems result in recurrent injury requiring readmission to a trauma center and /or death . METHODS A r and omized clinical trial was conducted to assess the effectiveness of two types of brief interventions to reduce drinking and the consequences of drinking . Trauma patients defined as at-risk alcohol users ( n=497 ) were r and omized into two treatment options : a brief personalized motivational intervention ( PMI ) , or brief information and advice ( BIA ) . After a brief assessment , PMI subjects received a motivational session , feedback letter , and two postdischarge telephone contacts , whereas the BIA group received a brochure and one postdischarge telephone contact . Both groups were reassessed at 6 and 12 months postinjury . RESULTS Both the PMI and BIA groups had statistically significant reductions in drinking , binge episodes , and consequences related to drinking that persisted from the 6- to the 12-month follow-up . However , although not statistically significant , for those classified as lower-level drinkers ( < or=1 drink per day ) , there was a consistent pattern of maintaining reductions for the PMI group at 12 months compared with the BIA group . CONCLUSION Our results suggest that brief interventions ( PMI and BIA ) that link alcohol consumption with trauma injury and consequences of drinking can be effective in reducing drinking and consequences related to drinking in a significant portion of at-risk nondependent drinkers This r and omized trial evaluated an intervention for reducing at-risk drinking practice s in a sample of 307 patients . Eligible drinking patterns included chronic drinking ( > or = 2 drinks per day in the past month ) , binge drinking ( > or = 5 drinks per occasion at least twice in the past month ) , and drinking and driving ( driving after > 2 drinks in the past month ) . Members of the intervention group received a message from their physician during their regularly scheduled visit , a self-help manual , written personalized feedback , and up to 3 telephone counseling calls . Dropout was significantly higher in the intervention than control group BACKGROUND Driving while impaired ( DWI ) recidivists with unresolved alcohol use problems pose an ongoing risk for traffic safety . Following conviction , many do not participate in m and ated alcohol evaluation and intervention programs , or continue to drink problematically after being relicensed . This study investigated if , in DWI recidivists with alcohol problems and not currently involved in DWI intervention , Brief Motivational Interviewing ( BMI ) produced greater reductions in risky drinking at 6- and 12-month follow-up compared to an information-advice control condition . Additional analyses explored whether BMI was associated with greater readiness to change , subsequent substance abuse treatment service utilization , and satisfaction compared to the control condition . METHODS Male and female recidivists with drinking problems and not currently engaged in DWI intervention were recruited , evaluated , and then r and omly assigned to receive 1 of 2 manualized interventions : 30-minute BMI session or information-advice . Participants , interviewers , research ers , and statisticians were blind to assignment . Outcomes were changed in : percent of risky drinking days ( i.e. , > or =3 st and ard drinks/d for males ; > or = 2 for females ) in the previous 6 months derived from the Timeline Followback , biomarkers of alcohol abuse ( GGT , AST , ALT , MCV ) by blood assay , and alcohol abuse-related behaviors using the MMPI-Mac scale . Data from the Readiness to Change Question naire , a substance abuse service utilization question naire , and the Client Satisfaction Scale were also collected . RESULTS Analyses revealed significant declines in risky drinking with both interventions . BMI ( n = 92 ) result ed in a 25 % reduction in risky drinking days at 12-month follow-up , which compared to the control intervention ( n = 92 ) represented a significant decline from 6-month levels . Exposure to BMI also produced significantly greater improvement at 6-month follow-up in a biomarker of alcohol abuse and a behavioral measure related to recidivism risk . Exploration of readiness to change , substance abuse service utilization , and satisfaction with intervention indicated a perception of BMI being more useful in coping with problems . CONCLUSIONS Brief MI approaches warrant further implementation and effectiveness research as an opportunistic DWI intervention strategy to reduce risks associated with alcohol use outside of clinical and DWI relicensing setting AIMS To assess the effectiveness of brief alcohol intervention on hazardous and harmful drinking in the 12-month period after a voluntary alcohol screening . METHODS At a large transport company , employees presenting to the occupational health services for a routine health and lifestyle check-up were offered to undertake an alcohol screening by means of self-report ( the Alcohol Use Disorders Identification Test-AUDIT ) and a biomarker ( carbohydrate-deficient transferrin in serum-CDT ) . Those screening positive for the AUDIT and /or CDT were r and omized to a brief or comprehensive intervention group or to a control group . An identical follow-up session was performed 12 months later . RESULTS Of 990 employees ( 68 % men ) that volunteered for the alcohol screening , 194 ( 20 % ) tested positive for the AUDIT and /or CDT . Among the 158 ( 81 % ) subjects who also attended the follow-up session , the frequency of positive screening results at baseline/follow-up were 51%/23 % for the AUDIT ( P < 0.0001 ) and 58%/34 % ( P < 0.0001 ) for CDT . However , there were no significant differences between the brief and comprehensive intervention groups or between the intervention groups and the control group . CONCLUSION The results suggested that alcohol screening and brief intervention performed in connection with routine health and lifestyle examinations in the workplace may be effective in reducing alcohol consumption . Given the lack of difference in outcome between the intervention groups and the control group , alcohol screening may in itself cause reduction in drinking . In addition , at least some of the positive effect may be explained by regression towards the mean Background Decreasing Injuries from ALcohol ( DIAL ) is a r and omised control trial of a telephone brief intervention ( BI ) with injured emergency department ( ED ) patients with high-risk alcohol use . Here the authors examine 12-month outcomes of the intervention 's effect on alcohol use , alcohol-related injuries and alcohol-related negative consequences . Methods ED research assistants recruited adult injured patients who screened positive for high-risk alcohol use and were to be discharged home . After discharge , all participants received by telephone an assessment of their alcohol use , alcohol-related injuries , and alcohol-related negative consequences and then were r and omised to treatment or st and ard care . Treatment consisted of two telephone sessions of BI focusing on risky alcohol use . Both groups were reassessed after 12 months . Results At 12 months , 249 ( 89 % ) participants completed follow-up assessment s. After using a log transformation , the difference in alcohol-related injuries between baseline and 12-month follow-up was greater in the BI group than the st and ard care group ( p=0.04 ) ; this is an effect size of Cohen 's d=0.21 . No difference between groups was found when comparing change in alcohol consumption and other alcohol-related negative consequences at 12 months . Conclusions These findings suggest that a telephone BI with injured ED patients may decrease alcohol-related injuries . Identifying patients with risky alcohol use in the ED and then subsequently delivering the intervention by telephone after discharge has promise as a model for BI and deserves further study BACKGROUND Brief motivational intervention ( BMI ) is one of the few effective strategies targeting alcohol consumption , but has not been tested in young men in the community . We evaluated the efficacy of BMI in reducing alcohol use and related problems among binge drinkers and in maintaining low-risk drinking among non-bingers . METHODS A r and om sample of a census of men included during army conscription ( which is m and atory for 20-year-old males in Switzerl and ) was r and omized to receive a single face-to-face BMI session ( N=199 ) or no intervention ( N=219 ) . A six-month follow-up rate was obtained for 88.7 % of the subjects . RESULTS Among binge drinkers , there was 20 % less drinking in the BMI group versus the control group ( incidence rate ratio=0.80 , confidence interval 0.66 - 0.98 , p=0.03 ) ; the BMI group showed a weekly reduction of 1.5 drinks compared to an increase of 0.8 drinks weekly in the control group . Among subjects who experienced one or more alcohol-related consequences over the last 12 months , there was 19 % less drinking in the BMI group compared to the control group ( incidence rate ratio=0.81 , confidence interval 0.67 - 0.97 , p=0.04 ) . Among non-bingers , BMI did not contribute to the maintenance of low-risk drinking . CONCLUSION BMI reduced the alcohol use of binge drinkers , particularly among those who experienced certain alcohol-related adverse consequences . No preventive effect of BMI was observed among non-bingers . BMI is a plausible secondary preventive option for young binge drinkers |
13,538 | 25,052,621 | Conclusion Pharmacist counseling is an intervention directed to patients ’ health-related needs that improve inter-professional and inter-institutional communication , by collaborating to integrate health services . | Background Pharmacists ’ counseling has improved health-related outcomes in many acute and chronic conditions .
Several studies have shown how pharmacists have been contributing to reduce morbidity and mortality related to drug-therapy ( MMRDT ) .
However , there still is a lack of review s that assemble evidence -based clinical pharmacists ’ counseling .
Equally , there is also a need to underst and structure characteristics , processes and technical contents of these clinical services .
Aim of the review To review the structure , processes and technical contents of pharmacist counseling or education reported in r and omized controlled trials ( RCT ) that had positive health-related outcomes . | OBJECTIVE To determine the effectiveness of structured adherence counseling by pharmacists on the eradication of Helicobacter pylori when using a st and ard drug treatment regimen . DESIGN R and omized controlled clinical trial . SETTING Nonprofit group- practice health maintenance organization ( HMO ) . PARTICIPANTS HMO primary care providers referred 1,393 adult dyspeptic patients for carbon 14 urea breath testing ( UBT ) . INTERVENTIONS Those whose tests were positive for H pylori ( 23.3 % ) were provided a st and ard antibiotic regimen and r and omly assigned to receive either usual-care counseling from a pharmacist or a longer adherence counseling session and a follow-up phone call from the pharmacist during drug treatment . All subjects were given the same 7-day course of omeprazole , bismuth subsalicylate , metronidazole , and tetracycline hydrochloride ( OBMT ) . Dyspepsia symptoms were recorded at baseline and following therapy . OUTCOMES The main outcome was eradication of H pylori as measured by UBT at 3-month follow-up . Secondary outcomes were patient satisfaction and dyspepsia symptoms at 3-month follow-up . RESULTS Of the 333 participants r and omly assigned to treatment , 90.7 % completed the 3-month follow-up UBT and question naires . Overall eradication rate with the OBMT regimen was 80.5 % with no significant difference in eradication rates between the 2 groups ( P=0.98 ) . Conclusions In this study , additional counseling by pharmacists did not affect self-reported adherence to the treatment regimen , eradication rates , or dyspepsia symptoms but did increase patient satisfaction BACKGROUND Hospitalization and subsequent discharge home often involve discontinuity of care , multiple changes in medication regimens , and inadequate patient education , which can lead to adverse drug events ( ADEs ) and avoidable health care utilization . Our objectives were to identify drug-related problems during and after hospitalization and to determine the effect of patient counseling and follow-up by pharmacists on preventable ADEs . METHODS We conducted a r and omized trial of 178 patients being discharged home from the general medicine service at a large teaching hospital . Patients in the intervention group received pharmacist counseling at discharge and a follow-up telephone call 3 to 5 days later . Interventions focused on clarifying medication regimens ; review ing indications , directions , and potential side effects of medications ; screening for barriers to adherence and early side effects ; and providing patient counseling and /or physician feedback when appropriate . The primary outcome was rate of preventable ADEs . RESULTS Pharmacists observed the following drug-related problems in the intervention group : unexplained discrepancies between patients ' preadmission medication regimens and discharge medication orders in 49 % of patients , unexplained discrepancies between discharge medication lists and postdischarge regimens in 29 % of patients , and medication nonadherence in 23 % . Comparing trial outcomes 30 days after discharge , preventable ADEs were detected in 11 % of patients in the control group and 1 % of patients in the intervention group ( P = .01 ) . No differences were found between groups in total ADEs or total health care utilization . CONCLUSIONS Pharmacist medication review , patient counseling , and telephone follow-up were associated with a lower rate of preventable ADEs 30 days after hospital discharge . Medication discrepancies before and after discharge were common targets of intervention OBJECTIVE To evaluate a training workshop for community pharmacy personnel to improve their counselling in smoking cessation based on the stage-of-change model . DESIGN A r and omised controlled trial of community pharmacies and pharmacy customers . SETTING All 76 non-city community pharmacies registered in Grampian , Scotl and , were invited to participate . Sixty-two pharmacies ( 82 % ) were recruited . SUBJECTS All the intervention pharmacy personnel were invited to attend the training ; 40 pharmacists and 54 assistants attended . A total of 492 customers who smoked ( 224 intervention , 268 controls ) were recruited during the 12-month recruitment period ( overall recruitment rate 63 % ) . MAIN OUTCOME MEASURES The perceptions of customers and pharmacy personnel of the pharmacy support and self-reported smoking cessation rates for the two groups of customers at one , four , and nine months . RESULTS The intervention customer respondents were significantly more likely to have discussed stopping smoking with pharmacy personnel , 85 % ( 113 ) compared with 62 % ( 99 ) of the controls ( p<0.001 ) . The former also rated their discussion more highly ; 34 % ( 45 ) of the intervention customers compared with 16 % ( 25 ) of the controls rated it as “ very useful ” ( p = 0.048 ) . Assuming non-responders had lapsed , one-month point prevalence of abstinence was cl aim ed by 30 % of intervention customers and 24 % of controls ( p = 0.12 ) ; four months ’ continuous abstinence was cl aim ed by 16 % of intervention customers and 11 % of controls ( p = 0.094 ) ; and nine months ’ continuous abstinence was cl aim ed by 12 % of intervention customers and 7 % of controls ( p = 0.089 ) . These trends in outcome were not affected by potential confounders ( sex , age , socioeconomic status , nicotine dependence , and type of nicotine replacement product used ) or adjustment for clustering . CONCLUSIONS The intervention was associated with increased and more highly rated counselling , and a trend toward higher smoking cessation rates , indicating that community pharmacy personnel have the potential to make a significant contribution to national smoking cessation targets OBJECTIVE To measure the effect of nurse practitioner and pharmacist consultations on the appropriate use of medications by patients . DESIGN We studied patients in the intervention arm of a r and omized controlled trial . The main trial intervention was provision of multidisciplinary team care and the main outcome was quality and processes of care for chronic disease management . SETTING Patients were recruited from a single publicly funded family health network practice of 8 family physicians and associated staff serving 10 000 patients in a rural area near Ottawa , Ont . PARTICIPANTS A total of 120 patients 50 years of age or older who were on the practice roster and who were considered by their family physicians to be at risk of experiencing adverse health outcomes . INTERVENTION A pharmacist and 1 of 3 nurse practitioners visited each patient at his or her home , conducted a comprehensive medication review , and developed a tailored plan to optimize medication use . The plan was developed in consultation with the patient and the patient 's doctor . We assessed medication appropriateness at the study baseline and again 12 to 18 months later . MAIN OUTCOME MEASURES We used the medication appropriateness index to assess medication use . We examined associations between personal characteristics and inappropriate use at baseline and with improvements in medication use at the follow-up assessment . We recorded all drug problems encountered during the trial . RESULTS At baseline , 27.2 % of medications were inappropriate in some way and 77.7 % of patients were receiving at least 1 medication that was inappropriate in some way . At the follow-up assessment s these percentages had dropped to 8.9 % and 38.6 % , respectively ( P < .001 ) . Patient characteristics that were associated with receiving inappropriate medication at baseline were being older than 80 years of age ( odds ratio [ OR ] = 5.00 , 95 % CI 1.19 to 20.50 ) , receiving more than 4 medications ( OR = 6.64 , 95 % CI 2.54 to 17.4 ) , and not having a university-level education ( OR = 4.55 , 95 % CI 1.69 to 12.50 ) . CONCLUSION We observed large improvements in the appropriate use of medications during this trial . This might provide a mechanism to explain some of the reductions in mortality and morbidity observed in other trials of counseling and advice provided by pharmacists and nurses . TRIAL REGISTRATION NUMBER NCT00238836 ( Clinical Trials.gov ) Abstract Objective To investigate the effects of compliance and periodic telephone counselling by a pharmacist on mortality in patients receiving polypharmacy . Design Two year r and omised controlled trial . Setting Hospital medical clinic . Participants 502 of 1011 patients receiving five or more drugs for chronic disease found to be non-compliant at the screening visit were invited for r and omisation to either the telephone counselling group ( n = 219 ) or control group ( n = 223 ) at enrolment 12 - 16 weeks later . Main outcome measures Primary outcome was all cause mortality in r and omised patients . Associations between compliance and mortality in the entire cohort of 1011 patients were also examined . Patients were defined as compliant with a drug if they took 80 - 120 % of the prescribed daily dose . To calculate a compliance score for the whole treatment regimen , the number of drugs that the patient was fully compliant with was divided by the total number of prescribed drugs and expressed as a percentage . Only patients who complied with all recommended drugs were considered compliant ( 100 % score ) . Results 60 of the 502 eligible patients defaulted and only 442 patients were r and omised . After two years , 31 ( 52 % ) of the defaulters had died , 38 ( 17 % ) of the control group had died , and 25 ( 11 % ) of the intervention group had died . After adjustment for confounders , telephone counselling was associated with a 41 % reduction in the risk of death ( relative risk 0.59 , 95 % confidence interval 0.35 to 0.97 ; P = 0.039 ) . The number needed to treat to prevent one death at two years was 16 . Other predictors included old age , living alone , rate of admission to hospital , compliance score , number of drugs for chronic disease , and non-treatment with lipid lowering drugs at screening visit . In the cohort of 1011 patients , the adjusted relative risk for death was 1.61 ( 1.05 to 2.48 ; P = 0.029 ) and 2.87 ( 1.80 to 2.57 ; P < 0.001 ) in patients with compliance scores of 34 - 66 % and 0 - 33 % , respectively , compared with those who had a compliance score of 67 % or more . Conclusion In patients receiving polypharmacy , poor compliance was associated with increased mortality . Periodic telephone counselling by a pharmacist improved compliance and reduced mortality . Trial registration International St and ard R and omised Controlled Trial Number Register : S RCT N48076318 BACKGROUND type 2 diabetes mellitus continues to increase in prevalence worldwide . Many factors have been cited as contributing to compliance , such as family and social support , education , number of tablets per dose , frequency of administration and health care provider communication . Toward these goals , the present study was developed to measure the effect offactors on glycemic control such as diabetes education by pharmacists , a diabetes disease booklet and special medication containers . MATERIAL AND METHOD A total of 360 volunteers with type 2 DM patients were recruited , participants were simple r and omized to control 180 and intervention 180 patients . Which intervention categorized to 4 groups ; all intervention groups received diabetes drug counseling by a pharmacist , one group received plus a diabetes booklet , one received plus special medical containers and the last group received all of them . The interventions were done at the 1st time of visit . Both the control and intervention groups were monitored for fasting plasma glucose and HbA1c at 0 , 3 , 6 months and glycemic level in both groups was compared . RESULTS After 3 months , mean fasting plasma glucose and HbA1c decreased wiih the intervention group vs. control group ( 152.36 + /- 39.73 to 131.52 + /- 35.22 mg% ) and ( 150.16 + /- 41.78 to 153.98 + /- 47.95 mg% ) respectively ; ( p < 0.001 ) . HbA1c level 8.16 + /- 1.44 to 7.72 + /- 1.26 vs 8.01 + /- 1.51 to 8.38 + /- 1.46 respectively ; ( p < 0.001 ) . After 6 months , mean fasting plasma glucose and HbA1c decreased with the intervention group vs. control group ( 152.36 + /- 39.73 to 145.20 + /- 46.07 mg% ) and ( 150.16 + /- 41.78 to 159.16 + /- 54.90 mg% ) respectively ; ( p < 0.013 ) . HbA1c level 8.16 + /- 1.44 to 7.91 + /- 1.27 vs. 8.01 + /- 1.51 to 8.80 + /- 1.36 respectively ; ( p < 0.001 ) . The most favorable glycemic outcome was the group that received all of the interventions ; mean FPG was reduced from 147.46 + /- 36.07 to 125.38 + /- 31.12 mg% ( p < 0.000 ) in 1nd visit ( 3 months later ) and still reducing effect on the 2nd visit ( 6 month later ) mean FPG from 147.46 + /- 36.07 to 130.21 + /- 33.96 mg% ( p < 0.016 ) also the same way in HbA 1c level . The group that received only drug counseling by pharmacist had no significant reduction in FPG and HbA1c . ( p > 0.05 ) . CONCLUSION Drug counseling by a pharmacist has little beneficial effect on diabetes management outcome compared to the diabetes booklet and special drug container . To improve glycemic control of type 2 DM is to integrate self-management in daily life , wide a variety of education , drug taken behavior and health care provider available communication produce improvement in patient management and is somewhat better when used in combination The object of the study was to evaluate outcomes of a r and omized clinical trial ( RCT ) of a pharmacist intervention for depressed patients in primary care ( PC ) . We report antidepressant ( AD ) use and depression severity outcomes at 6-months . The RCT was conducted between 1998 and 2000 in 9 eastern Massachusetts PC practice s. We studied 533 patients with major depression and /or dysthymia as determined by a screening test done at the time of a routine PC office visit . The majority of participants had recurrent depressive episodes ( 63.5 % with > /=4 lifetime episodes ) , and 49.5 % were taking AD medications at enrollment . Consultation in person and by telephone was performed by a clinical pharmacist who assisted the primary care practitioner ( PCP ) and patient in medication choice , dose , and regimen , in accordance with AHCPR depression guidelines . Six-month AD use rates for intervention patients exceeded controls ( 57.5 % vs. 46.2 % , P = .03 ) . Furthermore , the intervention was effective in improving AD use rates for patients not on ADs at enrollment ( 32.3 % vs. 10.9 % , P = .001 ) . The pharmacist intervention proved equally effective in subgroups traditionally considered difficult to treat : those with chronic depression and dysthymia . Patients taking ADs had better modified Beck Depression Inventory ( mBDI ) outcomes than patients not taking ADs , ( -6.3 points change , vs. -2.8 , P = .01 ) but the outcome differences between intervention and control patients were not statistically significant ( 17.7 BDI points vs. 19.4 BDI points , P = .16 ) . Pharmacists significantly improved rates of AD use in PC patients , especially for those not on ADs at enrollment , but outcome differences were too small to be statistically significant . Difficult-to-treat subgroups may benefit from pharmacists ' care Background Drug-related problems ( DRPs ) have been found to be associated with increased morbidity , mortality , and health costs . Objective To investigate whether the inclusion of pharmacists in a rehabilitation team influences the h and ling of DRPs in the ward and whether an intervention in hospital affects drug use after discharge . Setting The rehabilitation ward of a general hospital in Oslo , Norway . Methods Patients were r and omized into an intervention group ( IG ) or a usual care group ( CG ) . The IG patients were followed prospect ively by a pharmacist , who review ed the patients ’ drug therapies using information from their medical records and patient interviews . The pharmacist identified DRPs and suggested solutions during multidisciplinary team meetings . The IG patients received targeted drug counselling from the pharmacist before discharge . The drug therapy in the CG , for the period from study r and omization to discharge , was assessed retrospectively by the pharmacist , who identified DRPs and recorded how they were acted upon . Three months after discharge , pharmacists who were blinded to the patient r and omization , visited the patients at home and interviewed them about their medication . Main outcome measures : Types and frequencies of DRPs in the IG and CG were compared at hospital admission , at discharge , and 3 months after discharge . Results Of the 77 patients included , 40 belonged to the IG and 37 to the CG . Patient characteristics ( IG vs CG ) were as follows : age 73.5 versus 76.8 years ; female 58 versus 68 % ; mean number of drugs at admission 8.3 versus 7.8 ; and mean number of drugs at discharge 8.5 versus 7.7 . At admission , 4.4 DRPs per patient were recorded in the IG and 4.2 in the CG . Significantly more DRPs were acted upon and resolved in the IG ; at discharge , the IG had 1.2 DRPs per patient and the CG had 4.0 ( P < 0.01 ) . At the home visit , a significant difference between the groups was found : 1.63 versus 2.62 DRPs ( P = 0.02 ) for the IG and the CG , respectively . Conclusion Involvement of a pharmacist in drug-therapy management , including participation in multidisciplinary team discussion s , markedly improved the identification and resolution of DRPs during a hospital stay . The benefit persisted after discharge A r and omized trial of a pharmacist-delivered intervention ( PI ) versus usual care ( UC ) was conducted ; 689 subjects with known coronary heart disease were recruited from cardiac catheterization laboratories . Participants in the PI condition received 5 pharmacist-delivered telephone counseling calls post-hospital discharge . At one year , 65 % in the PI condition and 60 % in the UC condition achieved an LDL-C level < 100 mg/dL ( P = .29 ) ; mean statin adherence was 0.88 in the PI , and 0.90 in the UC ( P = .51 ) . The highest percentage of those who reached the LDL-C goal were participants who used statins as opposed to those who did not use statins ( 67 % versus 58 % , P = .05 ) . However , only 53 % and 56 % of the patients in the UC and PI conditions , respectively , were using statins . We conclude that a pharmacist-delivered intervention aim ed only at improving patient adherence is unlikely to positively affect outcomes . Efforts must be oriented towards influencing physicians to increase statin prescription rates BACKGROUND The practice of pharmaceutical care in primary care setting s in Thail and is currently not generally accepted . OBJECTIVE To evaluate the effect of pharmacist involvement in treatment with hypertensive patients in primary care setting s. METHODS The treatment objective was to stabilize the blood pressure ( BP ) of hypertensive patients in accordance with the Joint National Committee on Prevention , Detection , Evaluation and Treatment of High Blood Pressure guidelines . Patients were r and omly assigned to a pharmacist-involved group ( treatment ) or a group with no pharmacist involvement ( control ) . Pre- and post-test BPs , tablet counts , lifestyle modifications , and pharmacists ’ recommendations were recorded . The 6-month study was carried out in Mahasarakham University pharmacy and 2 primary care units . Patients were monitored monthly by review ing their medications and supported by providing pharmaceutical care and counseling . RESULTS From a total of 235 patients , the treatment group ( n = 118 ) had a significant reduction in both systolic ( S ) and diastolic ( D ) BP compared with the 117 patients of the control group ( p = 0.037 , 0.027 , respectively ) . The 158 patients ( 76 treatment , 82 control ) with BPs 140/90 mm Hg at the beginning of the study showed significant BP reductions ( p = 0.002 SBP , 0.008 DBP ) . The proportion of 158 patients whose BP became stabilized was higher in the treatment group ( p = 0.017 ) . The treatment group showed significantly better adherence ( p = 0.014 ) and exercise control ( p = 0.012 ) at the end of the study . Physicians accepted 42.72 % of medication modifications and 5.34 % of the suggestions for additional investigations . CONCLUSIONS Hypertensive patients who received pharmacist input achieved a significantly greater benefit in BP reduction , BP control , and improvement in adherence rate and lifestyle modification WHAT IS KNOWN AND OBJECTIVE Pharmacists have been involved in providing comprehensive interventions to osteoporosis patients , but pharmaceutical care issues ( PCIs ) encountered during such interventions have not been well documented . Therefore , the aim of this study was to document PCIs encountered by post-menopausal osteoporotic women prescribed bisphosphonates . METHODS A r and omized controlled study was conducted from September 2005-February 2009 in the University Malaya Medical Centre , Malaysia . This main intervention study measured the effects of pharmaceutical care on medication adherence , persistence , quality of life , knowledge and patient satisfaction . However , this manuscript is part of the main intervention study and focuses only on the PCIs encountered . INCLUSION CRITERIA post-menopausal women diagnosed with osteoporosis ( T-score≤-2·5/low-trauma fracture ) and prescribed weekly alendronate/risedronate . EXCLUSION CRITERIA those with metabolic bone disease and could not communicate in English . The PCIs identified were collected via personal interviews or telephone calls , and each participant was followed-up for a period of 2 years . All PCIs were discussed with and confirmed by a physician . RESULTS AND DISCUSSION Of the 198 participants recruited , 64 ( 32·3 % ) experienced adverse effects because of bisphosphonates whereas one participant ( 0·5 % ) refused to start bisphosphonates because of fear of adverse effects . Most adverse effects [ 50 ( 74·6 % ) ] were reported during the first 3 months of therapy with gastrointestinal problems being the main issue [ 23 ( 11·6 % ) ] . Of the nine participants ( 4·5 % ) who discontinued bisphosphonates , only three agreed to take another medication . From the 97 PCIs identified , 77 issues could be classified as drug-related problems [ according to the Pharmaceutical Care Network Europe Classification v6·2 ] . There were 87 causes , 178 interventions and 77 outcomes . The main problem and cause of the PCIs encountered were adverse drug events ( 83·1 % and 74·7 % respectively ) , whereas the main intervention provided was patient counselling ( 41·0 % ) . All problems were solved ( 98·5 % ) except for one because of the lack of cooperation of a patient . After 2 years , 36 participants ( 20 % ) were no longer persistent with therapy , 19 ( 10·6 % ) did not have clinic follow-up and 53 ( 26·8 % ) did not have a bone mineral density scan . WHAT IS NEW AND CONCLUSION The main PCIs identified were related to the use of bisphosphonates and its adverse effects . The study showed that the presence of a clinical pharmacist has enabled patients to voice their medication-related issues and to allow appropriate recommendations and actions to be taken to resolve these issues Background The roles of pharmacists have evolved from product oriented , dispensing of medications to more patient-focused services such as the provision of pharmaceutical care . Such pharmacy service is also becoming more widely practised in Malaysia but is not well documented . Therefore , this study is warranted to fill this information gap by identifying the types of pharmaceutical care issues ( PCIs ) encountered by primary care patients with diabetes mellitus , hypertension or hyperlipidaemia in Malaysia . Methods This study was part of a large controlled trial that evaluated the outcomes of multiprofessional collaboration which involved medical general practitioners , pharmacists , dietitians and nurses in managing diabetes mellitus , hypertension and hyperlipidaemia in primary care setting s. A total of 477 patients were recruited by 44 general practitioners in the Klang Valley . These patients were counselled by the various healthcare professionals and followed-up for 6 months . Results Of the 477 participants , 53.7 % had at least one PCI , with a total of 706 PCIs . These included drug-use problems ( 33.3 % ) , insufficient awareness and knowledge about disease condition and medication ( 20.4 % ) , adverse drug reactions ( 15.6 % ) , therapeutic failure ( 13.9 % ) , drug-choice problems ( 9.5 % ) and dosing problems ( 3.4 % ) . Non-adherence to medications topped the list of drug-use problems , followed by incorrect administration of medications . More than half of the PCIs ( 52 % ) were classified as probably clinical ly insignificant , 38.9 % with minimal clinical significance , 8.9 % as definitely clinical ly significant and could cause patient harm while one issue ( 0.2 % ) was classified as life threatening . The main causes of PCIs were deterioration of disease state which led to failure of therapy , and also presentation of new symptoms or indications . Of the 338 PCIs where changes were recommended by the pharmacist , 87.3 % were carried out as recommended . Conclusions This study demonstrates the importance of pharmacists working in collaboration with other healthcare providers especially the medical doctors in identifying and resolving pharmaceutical care issues to provide optimal care for patients with chronic diseases OBJECTIVE To determine the effect of a home-based intervention ( HBI ) on the frequency of unplanned readmission and out-of-hospital death among patients discharged home from acute hospital care . DESIGN A r and omized controlled trial comparing HBI with usual care ( UC ) . SETTING A tertiary referral hospital servicing the northwestern region of Adelaide , South Australia . PARTICIPANTS Medical and surgical patients ( n = 762 ) discharged home after hospitalization . INTERVENTION Home-based intervention ( n = 381 ) consisted of counseling of all patients before discharge followed by a single home visit ( by a nurse and pharmacist ) to those patients considered to be at high risk of readmission ( n = 314 ) in order to optimize compliance with and knowledge of the treatment regimen , identify early clinical deterioration , and intensify follow-up of such patients where appropriate . MEASUREMENTS The primary endpoint was the number of unplanned readmissions plus out-of-hospital deaths over a 6-month follow-up period . RESULTS During the study follow-up , the major endpoint occurred most commonly in the UC group ( 217 vs 155 episodes : P < .001 ) . Overall , the HBI group demonstrated fewer unplanned readmissions ( 154 vs 197 : P = .022 ) , out-of-hospital deaths ( 1 vs. 20 : P < .001 ) , total deaths ( 12 vs. 29 : P = .006 ) , emergency department attendances ( 236 vs 314 : P < .001 ) , and total days of hospitalization ( 1452 vs 1766 : P < .001 ) . There was a disproportionate reduction in multiple events among HBI patients ( P = .035 ) . Hospital-based costs of health care during study follow-up tended to be lower in the HBI group ( $ A2190 vs $ A2680 per patient : P = .102 ) . Mean cost of HBI was $ A190 per patient visited , whereas other community-based health care costs were similar for both groups . CONCLUSIONS Among high-risk patients discharged from acute hospital care , HBI is beneficial in limiting unplanned readmissions and reducing risk of out-of-hospital death . It may be particularly cost-effective if applied selectively to patients with a history of frequent unplanned hospital admission OBJECTIVES To describe the processes of care used by community pharmacists participating in the Pharmaceutical Care Research and Education Project ( PREP ) in terms of drug-related problems ( DRPs ) , pharmacists ' recommendations , and status of DRPs at follow-up , and to determine characteristics associated with DRPs . DESIGN Descriptive analysis of the treatment group from a larger r and omized , controlled cluster design . SETTING Five independent community pharmacies in Alberta . PARTICIPANTS One hundred fifty-nine patients who were covered under Alberta Health and Wellness 's senior drug benefit plan ( i.e. , 65 years or older ) , were taking three or more medications concurrently according to pharmacy records , were able to complete telephone interviews as determined by pharmacists , maintained residence in Alberta for 12 of the 15 study months , agreed to receive their prescription medications only from the study pharmacy during the study period , and provided informed consent . MAIN OUTCOME MEASURES Frequency of DRPs , recommendations , status of DRPs , and analysis of clinical results as determined during pharmacists ' follow-up care . RESULTS In telephone surveys , patients reported taking 4.7 prescription medications per day , but pharmacists documented 8.7 prescription medications per day in their records . Pharmacists documented 559 DRPs , a mean ( + /- SD ) of 3.9+/-3.2 problems per patient . Approximately 39 % of problems were actual DRPs , while 60 % were potential DRPs . Medical conditions associated most frequently with a DRP involved the respiratory , cardiovascular , and musculoskeletal systems . The most common DRP categories were " patient requires drug therapy " or " patient requires influenza or pneumococcal vaccination . " Pharmacists wrote 551 initial clinical notes using the subjective , objective , assessment , plan ( SOAP ) format , and they recorded 346 follow-up interventions , also using SOAP notes . Counseling , preventive consultations , and clinical monitoring represented 40 % of their recommendations . In 80 % of situations , the pharmacist made the recommendation directly to the patient . On follow-up , 40 % of the 559 DRPs identified were resolved , controlled , or improved . Patients accepted 76 % of pharmacists ' recommendations , and physicians accepted 72 % of pharmacists ' suggested resolutions of DRPs . Pharmacists were more likely to follow up about actual DRPs , as compared with potential ones ; overall , they followed up on 62 % of identified DRPs . CONCLUSION Pharmacists identified more DRPs for study patients than previous community-based , observational studies have reported . Undertreatment appears to be a prevalent DRP . Community pharmacists ' recommendations to prevent and resolve DRPs were made primarily to patients and were well accepted . More follow-up was needed for all DRPs . When follow-up occurred , the DRP results generally showed improvement Objective Studies have demonstrated that hypertension remains inadequately managed throughout the world , with lack of adherence to BP-lowering medication being a major factor . The aim of the present study was to evaluate if a pharmaceutical care program could improve antihypertensive medication adherence and blood pressure control . Setting This study was conducted in a secondary care hypertension/dyslipidemia outpatient clinic in the university teaching hospital of Cova da Beira Hospital Centre , Covilhã , located in the Eastern Central Region of Portugal . Method This report evaluates the pharmacist ’s interventions during a prospect i ve r and omised controlled trial , from July 2009 to June 2010 . Patients with diagnosis of essential hypertension attending the clinic for routine follow-up were r and omly allocated either to a control group ( no pharmaceutical care ) or to an intervention group ( quarterly follow-up by a hospital pharmacist during a 9-month period ) . The pharmacist interventions , aim ed to increase medication adherence and blood pressure control , involved educational interventions and counselling tips directed to the patient . Main outcome measure Systolic blood pressure , diastolic blood pressure and blood pressure control ( according to JNC 7 guidelines ) assessed at the baseline visit and at the end of pharmaceutical care were the main outcome measures . Blood pressure measurements were performed by blinded nurses . Medication adherence was also evaluated , using a vali date d question naire at baseline and at the end of investigation . Results A total of 197 hypertensive patients were r and omly assigned to the study ( 99 in the control group and 98 in the intervention group ) . Although there were no significant differences ( P > 0.05 ) in both groups concerning mean age , gender , body mass index , and antihypertensive pharmacotherapy , blood pressure control was higher in the intervention group ( P = 0.005 ) at the end of the study . Significant lower systolic blood pressure ( −6.8 mmHg , P = 0.006 ) and diastolic blood pressure ( −2.9 mmHg , P = 0.020 ) levels were observed in the intervention group . Medication adherence was also significantly higher in the intervention group at the end of the study ( 74.5 % vs. 57.6 % , P = 0.012 ) . Conclusion Pharmacist intervention can significantly improve medication adherence and blood pressure control in patients treated with antihypertensive agents BACKGROUND Blood pressure ( BP ) control in patients with diabetes mellitus is difficult to achieve and current patterns are suboptimal . Given increasing problems with access to primary care physicians , community pharmacists and nurses are well positioned to identify and observe these patients . This study aim ed to determine the efficacy of a community-based multidisciplinary intervention on BP control in patients with diabetes mellitus . METHODS We performed a r and omized controlled trial in 14 community pharmacies in Edmonton , Alberta , Canada , of patients with diabetes who had BPs higher than 130/80 mm Hg on 2 consecutive visits 2 weeks apart . Care from a pharmacist and nurse team included a wallet card with recorded BP measures , cardiovascular risk reduction education and counseling , a hypertension education pamphlet , referral to the patient 's primary care physician for further assessment or management , a 1-page local opinion leader-endorsed evidence summary sent to the physician reinforcing the guideline recommendations for the treatment of hypertension and diabetes , and 4 follow-up visits throughout 6 months . Control-arm patients received a BP wallet card , a pamphlet on diabetes , general diabetes advice , and usual care by their physician . The primary outcome measure was the difference in change in systolic BP between the 2 groups at 6 months . RESULTS A total of 227 eligible patients were r and omized to intervention and control arms between May 5 , 2005 , and September 1 , 2006 . The mean ( SD ) patient age was 64.9 ( 12.1 ) years , 59.9 % were male , and the mean ( SD ) baseline systolic/diastolic BP was 141.2 (13.9)/77.3 ( 8.9 ) mm Hg at baseline . The intervention group had an adjusted mean ( SE ) greater reduction in systolic BP at 6 months of 5.6 ( 2.1 ) mm Hg compared with controls ( P = .008 ) . In the subgroup of patients with a systolic BP greater than 160 mm Hg at baseline , BP was reduced by an adjusted mean ( SE ) of 24.1 ( 1.9 ) mm Hg more in intervention patients than in controls ( P < .001 ) . CONCLUSION Even in patients who have diabetes and hypertension that are relatively well controlled , a pharmacist and nurse team-based intervention result ed in a clinical ly important improvement in BP . Trial Registration clinical trials.gov Identifier : NCT00374270 Objective To explore the best interventions and working patterns of clinical pharmacists in pediatrics and to determine the effectiveness of clinical pharmacists in pediatrics . Methods We conducted a r and omized controlled trial of 160 pediatric patients with nerve system disease , respiratory system disease or digestive system disease , who were r and omly allocated into two groups , with 80 in each group . Interventions by clinical pharmacists in the experimental group included answering questions of physicians and nurses , giving advice on treating patients , checking prescriptions and patient counseling at discharge . In the control group , patients were treated without clinical pharmacist interventions . Results Of the 109 interventions provided by clinical pharmacists during 4 months , 47 were consultations for physicians and nurses , 31 were suggestions of treatment , with 30 accepted by physicians ( 96.77 % ) and 31 were medical errors found in 641 prescriptions . Five adverse drug reactions were su bmi tted to the adverse drug reaction monitoring network , with three in the experimental group and two in the control group . The average length of stay ( LOS ) for patients with respiratory system diseases in the experimental group was 6.45 days , in comparison with 10.83 days in the control group , which was statistically different ( p value<0.05 ) ; Average drug compliance rate in the experimental group was 81.41 % , in comparison with 70.17 % of the control group , which was statistically different ( p value<0.05 ) . Cost of drugs and hospitalization and rate of readmission in two weeks after discharge in the two groups were not statistically different . Conclusion Participation by clinical pharmacists in the pharmacotherapy of pediatric patients can reduce LOS of patients with respiratory system disease and improve compliance rate through discharge education , showing no significant effects on prevention of ADR , reduction of cost of drugs and hospitalization and readmission rate in two weeks . Trial Registration Chinese Clinical Trial Registry OBJECTIVE To test a new prescription counseling method termed " patient-guided counseling " ( PGC ) in community pharmacies . DESIGN Post-test experimental design in which subjects were r and omized to three groups . SETTING Six community pharmacies ( three chain and three independent ) . PATIENTS Patients presenting new prescriptions . INTERVENTIONS Patients were r and omly assigned to one of three comparison groups . The PGC group was given a written prompt instructing them to write any questions they wished to ask about their prescription or their medical condition . The pharmacist then incorporated these questions into the subsequent verbal counseling . A second group was given a written prompt encouraging them to ask the pharmacist questions . This was followed by customary verbal counseling . A third group served as the control . No prompts were provided , but the pharmacist did provide customary verbal counseling . MAIN OUTCOME MEASURES Patients ' demographics , recall of medication information , and satisfaction with counseling . Patients were contacted by telephone 5 days after the start of drug therapy to measure compliance . Pharmacists rated their satisfaction with the information communicated and with their interactions with patients . RESULTS Compared with customary verbal counseling , the PGC method was associated with more supplemental questions asked by the patient . Compared with the other two methods , PGC was associated with greater pharmacist satisfaction with the information communicated and slightly longer counseling sessions . No significant differences were found for patients ' overall satisfaction with counseling , recall of information , and compliance . CONCLUSION In the community pharmacy setting , PGC fosters patient participation in medication counseling , a necessary element for the provision of pharmaceutical care Objective : To investigate the effect of a pharmacist care program on cardiovascular risks in type 2 diabetic patients . Methods : A 9-month , prospect i ve , r and omized , controlled study was conducted in a public hospital in Hong Kong . Patients in the intervention group had regular drug-counseling sessions with pharmacists in addition to routine medical care , whereas patients in the control group received only routine medical care . The primary outcome was the change in coronary heart disease ( CHD ) risk . Results : A total of 105 patients completed the study . Patients in the intervention group had a statistically significant reduction in CHD risk compared to those in the control group ( −1.64 % ± 3.56 % ; n = 51 vs −0.01 % ± 3.08 % ; n = 54 , P = .013 ) . For stroke , a reduction in risk was noted in the intervention group , while an increased risk was noted in the control group ( −1.06 % ± 1.82 % vs 0.31 % ± 2.51 % , P = .002 ) . In addition , hemoglobin A1c levels were significantly reduced in the intervention group compared with the control group ( −1.57 % ± 1.50 % vs –0.40 % ± 1.19 % , P < .001 ) ; a similar profile was seen with low-density lipoprotein cholesterol ( −0.36 ± 0.76 vs −0.03 ± 0.74 , P = .026 ) . Furthermore , there were nonsignificant improvements in high-density lipoprotein cholesterol , triglyceride , and blood pressure in the intervention group . The increased level of underst and ing regarding medications in the intervention group was statistically significant ( P < .001 ) , yielding a better enhancement in compliance compared with patients in the control group ( 22.5 % ± 13.4 % vs 2.0 % ± 5.0 % , P < .001 ) . Conclusion : The pharmacist care program implemented in this study demonstrated a significant cardiovascular risk reduction in type 2 diabetic patients ; therefore such a program would be a valuable addition to a multidisciplinary care of diabetic patients The impact on the care of breast cancer patients , of a pharmacy technician-led medication review and counselling clinic , provided in an outpatient setting , was investigated using a controlled r and omised study . Compared to the controls , clinic patients showed a significantly improved level of underst and ing of their chemotherapy support medication ( 95 % CI for difference in mean knowledge rating scores=2.165–2.826 , P<0.001 ) and a significant reduction in the median number of support items required ( two compared to five in the control , P<0.001 ) . This result ed in a significant reduction in mean medication expenditure per patient ( £ 26.70 vs £ 10.20 , 95 % CI for the mean difference in cost £ 6.72–£26.26 , P<0.001 ) . The clinic was also associated with significant reductions in chemotherapy delays ( P<0.001 ) and dose reductions due to side effects ( P=0.003 ) . Other benefits from the clinic were a reduction in pharmacy dispensing time and a highly significant reduction in pharmacy time spent resolving post-clinic prescription queries ( P<0.001 ) . Taking into account the initial technician training cost , the scheme represented an annual saving to the Trust of over £ 15 000 . The clinic serves as a model for those wishing to improve outpatient services to breast cancer patients The prevalence of diabetes in India has grown over the past decade . Diabetic patients develop complications due to poor awareness regarding the disease and inadequate glycemic control . Patient education is the most effective way to lessen the complications of diabetes and its management . A total of 207 ( 85 males and 122 females ) type 2 diabetes mellitus patients were enrolled and r and omized into test and control groups . Patients in the test group received counseling at each visit and information leaflets from the pharmacist ; the control group patients received counseling and information leaflets only at the end of the study . A vali date d knowledge , attitude , and practice ( KAP ) question naire was administered to both test and control group patients at baseline and at final follow-up to assess awareness regarding disease management . Glucose and lipid levels were also evaluated at baseline and final follow-up in both the groups . At the end of the study , the KAP score of test group patients improved significantly ( P<0.0001 ) , whereas no significant changes were observed in control group patients . The postpr and ial blood glucose ( PPBG ) levels decreased significantly in the test group . Total cholesterol ( TC ) , triglycerides ( TGL ) , and low density lipoprotein levels ( LDL ) also showed a decrease in the test group . Thus , our study reveals that pharmacist counseling might be an important element in diabetes management programs OBJECTIVES To determine whether an enhanced compliance program ( ECP ) improves patient compliance with bismuth subsalicylate , metronidazole , and tetracycline hydrochloride ( BMT ) triple therapy for the treatment of Helicobacter pylori infection and to identify factors that affect compliance with therapy . DESIGN A r and omized controlled trial conducted in 4 staff-model health centers of a health maintenance organization in Massachusetts . PATIENTS AND METHODS A total of 125 patients 18 years of age or older with peptic ulcer disease or dyspepsia whose clinicians prescribed BMT triple therapy for 14 days were r and omized to a control group or to the ECP group . The ECP group received medication counseling ( written and oral ) from a pharmacist , along with a medication calendar and a minipillbox , as well as a follow-up telephone call after initiation of therapy . Compliance was assessed by a pill count , and factors affecting adherence to the regimen were identified by patients ' reports . RESULTS There was no statistically significant difference between the 2 groups in the number of patients taking more than 60 % of the medications ( 89 % of the control group vs 95 % of the ECP group ; P>.30 ) . However , there was a statistically significant difference in the number of patients taking more than 90 % of the medications ( 67 % of the control group vs 89 % of the ECP group ; P<.01 ) . An intention-to-treat analysis confirmed these results . The most frequently reported adverse effect was gastrointestinal intolerance . Other factors reported to affect compliance included the frequency of dosing and the number of pills . CONCLUSIONS These findings suggest that although adverse effects were common , most patients were able to complete 60 % or more of the 2-week regimen . An ECP further improved the percentage of medications taken Objectives To implement and assess hospital-based pharmaceutical care services for patients with asthma . Methods A prospect i ve , r and omized , controlled study was conducted in Shaab teaching hospital , Khartoum , Sudan . Patients were allocated r and omly either in the intervention group ( 60 ) or control group ( 40 ) patients . The drug therapy of asthma for the patients in the intervention group was review ed by a trained pharmacist , and interventions were suggested to the attending physicians for the identified problems . Intervention patients received comprehensive medication counselling and asthma education every 2 weeks , while the control group received the routine medical consultation and dispensing services . The outcome measures were recorded using structured forms at baseline and monitored during a follow-up of every two weeks for 6 months in both groups . Data were analyzed using SPSS version 13 , level of significance was p<0.05 . Results At the end of the study period the mean reduction in frequency of acute attacks ( 1.91 ; SD=0.18 vs. 1.0 ; SD=0.14 ; p=0.03 ) , nocturnal asthma symptoms ( 3.5 ; SD=0.3 vs. 1.1 ; SD=0.2 ; p=0.02 ) and frequency of using inhaled β2 agonists per week ( 19.9 ; SD= 2.1 vs. 3.3 ; SD=0.3 ; p=0.01 ) were significantly greater in the intervention group compared to control . A significant mean reduction ( p=0.002 ) in the days of sickness/week was in the intervention group , while in control group there was an increase in mean days of sickness/week . The intervention group showed a significant greater improvement in the score for assessing the inhalation technique ( p<0.001 ) , patient ’s knowledge about asthma ( p<0.001 ) , and its drug-therapy ( p=0.01 ) compared with control . Conclusion The present findings suggest that pharmacist ’s intervention can have positive impact on asthma-related outcomes in patients BACKGROUND Despite the availability of proven therapies , outcomes in patients with heart failure ( HF ) remain poor . In this 2-stage , multicenter trial , we evaluated the effect of a disease management program on clinical and economic outcomes in patients with HF . METHODS AND RESULTS In Stage 1 , a pharmacist or nurse assessed each patient and made recommendations to the physician to add or adjust angiotensin-converting enzyme ( ACE ) inhibitors and other HF medications . Before discharge ( Stage 2 ) , patients were r and omized to a patient support program ( PSP ) ( education about HF , self-monitoring , adherence aids , newsletters , telephone hotline , and follow-up at 2 weeks , then monthly for 6 months after discharge ) or usual care . In Stage 1 ( 766 patients ) ACE inhibitor use increased from 58 % on admission to 83 % at discharge ( P < .0001 ) , and the daily dose ( in enalapril equivalents ) increased from 11.3 + /- 8.8 mg to 14.5 + /- 8.8 mg ( P < .0001 ) . In Stage 2 ( 276 patients ) there was no difference in ACE inhibitor adherence , but a reduction in cardiovascular-related emergency room visits ( 49 versus 20 , P = .030 ) , hospitalization days ( 812 versus 341 , P = .003 ) , and cost of care ( 2,531 Canadian dollars less per patient ) in favor of the PSP . CONCLUSION Simple interventions can improve ACE inhibitor use and patient outcomes Background As a result of the previous part of this trial , many patients with cardiovascular disease were expected to receive a statin for the first time . In order to provide these patients with comprehensive information on statins , as recommended by professional guidance , education at first and second dispensing of statins had to be implemented . This study was design ed to assess the effectiveness of an intensive implementation program targeted at pharmacy project assistants on the frequency of providing education at first dispensing ( EAFD ) and education at second dispensing ( EASD ) of statins in community pharmacies . Methods The participating community pharmacies were clustered on the basis of local collaboration , were numbered by a research assistant and subsequently an independent statistician performed a block r and omization , in which the cluster size ( number of pharmacies in each cluster ) was balanced . The pharmacies in the control group received a written manual on the implementation of EAFD and EASD ; the pharmacies in the intervention group received intensive support for the implementation . The impact of the intensive implementation program on the implementation process and on the primary outcomes was examined in a r and om coefficient logistic regression model , which took into account that patients were grouped within pharmacy clusters . Results Of the 37 pharmacies in the intervention group , 17 pharmacies ( 50 % ) provided EAFD and 12 pharmacies ( 35.3 % ) provided EASD compared to 14 pharmacies ( 45.2 % , P = 0.715 ) and 12 pharmacies ( 38.7 % , P = 0.899 ) , respectively , of the 34 pharmacies in the control group . In the intervention group a total of 72 of 469 new statin users ( 15.4 % ) received education and 49 of 393 patients with a second statin prescription ( 12.5 % ) compared to 78 of 402 new users ( 19.4 % , P = 0.944 ) and 35 of 342 patients with a second prescription ( 10.2 % , P = 0.579 ) in the control group . Conclusion The intensive implementation program did not increase the frequency of providing EAFD and EASD of statins in community pharmacies . Trial Registration clinical trials.gov Objective : To evaluate the impact of a hospital based community liaison pharmacy service on a range of outcomes in patients aged more than 55 years and taking more than 3 prescribed drugs , who had been admitted to the medical unit of a district general hospital in Northern Irel and . Methods : Having recruited 243 patients , a total of 162 patients completed the full protocol ( 81 r and omly assigned to intervention and 81 to control ; mean age of control patients 75 years ; mean age of intervention patients 73 years ) . The interventions by the community liaison pharmacist included : preparation of an accurate medication record following a full review of current medication use ; medication counselling ; provision of a medicines record sheet informing the patient how to take their drugs ; provision of a pharmaceutical discharge letter detailing changes made to drug therapy ( this was faxed to the patient 's GP and community pharmacist on the day of discharge ) ; provision of a Medicines Helpline . Results : The key findings were as follows : problems were identified in 80 % of the intervention patients ' prescription charts , 49 % of which related to drug omissions from the patients ' domiciliary prescriptions . The GP practice record was the most accurate ( mean error rate 12.6 % ) while the GP referral letter was the least accurate ( mean error rate 47.3 % ) source of medication information . Drugs patients brought to hospital were also an inaccurate source ( mean error rate 44.0 % ) . The intervention group patients , when compared with control patients , had a significant reduction ( P=0.005 ) in drug mismatch between drugs prescribed at discharge and taken at home , and had a greater knowledge of their drug regimen 10–14 days after discharge ( P |Ld 0.001 ) . The vast majority of patients ( 96 % ) felt that the provision of a medicine helpline was a useful service . Conclusions : The study indicated clear benefits from the involvement of a hospital based community liaison pharmacist in achieving seamless pharmaceutical care between the primary and secondary healthcare setting A controlled , r and omized study was conducted in two chain pharmacies to determine the clinical value of comprehensive pharmacy services for hypertensive patients in a chain pharmacy setting . Twenty-seven patients were enrolled as intervention participants with 26 control subjects . Monthly services for the intervention group included blood pressure and heart rate assessment s and counseling on lifestyle modifications and drug therapy . Control patients received initial and final blood pressure measurements and minimal counseling . Both study and control groups completed quality -of-life question naires upon entering and completing the study . Results showed that blood pressure control was significantly improved in the study group . Compliance rates as well as energy/fatigue scores ( a quality -of-life scale ) improved in the study group compared with the control population . Community pharmacists in chain stores could have a beneficial effect on the health care of large numbers of patients if pharmaceutical care programs were developed OBJECTIVE --To investigate whether a reminder chart improved patients ' compliance with their drug regimen after discharge from hospital . DESIGN -- Patients were r and omly allocated to one of four groups . Two groups received the reminder chart : one also received routine counselling from a nurse and the other received structured counselling from a pharmacist , which included an explanation of the reminder chart . The other two groups received only counseling , either from a nurse or from a pharmacist . Patients were visited about 10 days later : they were question ed about their drug regimen , and their compliance was measured by tablet counting . SETTING --The pharmacy in a district general hospital and patients ' homes . PATIENTS --197 patients being discharged from hospital who were regularly taking two or more drugs . INTERVENTION -- An individualised reminder chart , which listed each person 's medicines and when they were to be taken and was automatically generated by a medicine labelling computer . MAIN OUTCOME MEASURES --Patient 's compliance with and knowledge of their drug regimen . MAIN RESULTS --Of the patients who received the reminder chart , 83 % ( 95 % confidence interval 74 % to 90 % ) correctly described their dose regimen compared with 47 % ( 37 % to 58 % ) of those without the chart ( p < 0.001 ) . The mean compliance score was 86 % ( 81 % to 91 % ) in both groups not given the reminder chart ; 91 % ( 87 % to 94 % ) in the group given the chart without an explanation ; and 95 % ( 93 % to 98 % ) in the group given the chart and an explanation . A mean compliance score of > 85 % was achieved by 63 % ( 53 % to 73 % ) of patients without a reminder chart and by 86 % ( 78 % to 93 % ) of those receiving the chart ( p < 0.001 ) . CONCLUSIONS --An automatically generated reminder chart is a practical and cost effective aid to compliance Objective To assess the effects of pharmacists giving advice to meet patients ’ needs after starting a new medicine for a chronic condition . Method A prospect i ve health technology assessment including a r and omised controlled trial of a pharmacist-delivered intervention to improve adherence using a central ised telephone service to patients at home in Engl and . Patients were eligible for recruitment if they were receiving the first prescription for a newly prescribed medication for a chronic condition and were 75 or older or suffering from stroke , cardiovascular disease , asthma , diabetes or rheumatoid arthritis . Main outcome measures Incidence of non-adherence , problems with the new medicine , beliefs about the new medicine , safety and usefulness of the interventions . Results Five hundred patients consented and were r and omised . At 4-week follow-up , non-adherence was significantly lower in the intervention group compared to control ( 9 % vs. 16 % , P = 0.032 ) . The number of patients reporting medicine-related problems was significantly lower in the intervention group compared to the control ( 23 % vs. 34 % , P = 0.021 ) . Intervention group patients also had more positive beliefs about their new medicine , as shown by their higher score on the “ necessity-concerns differential ” ( 5.0 vs. 3.5 , P = 0.007 ) . The phone calls took a median of 12 min each . Most advice was judged by experts to be safe and helpful , and patients found it useful . Conclusion Overall , these findings show benefits from pharmacists meeting patients ’ needs for information and advice on medicines , soon after starting treatment . While a substantially larger trial would be needed to confirm that the effect is real and sustained , these initial findings suggest the service may be safe and useful to patients RATIONALE , AIMS AND OBJECTIVES To determine whether an increased input by clinical pharmacists at each stage of the patient 's hospital journey , from admission through discharge , result ed in an enhanced level of patient care as measured by a number of clinical and economic outcomes . METHODS This project was design ed to address medicines management issues in patients deemed at risk of drug-related problems . During the project , these latter patients at the time of admission were r and omly assigned to an integrated medicines management ( IMM ) service group ( n = 371 ) or regular hospital care group ( n = 391 ) . The IMM service involved comprehensive pharmaceutical care provided by a pharmacy team throughout each of three stages : patient admission , inpatient monitoring and counselling , and patient discharge . RESULTS Patients who received the IMM service benefited from a reduced length of hospital stay [ by 2 days ( P = 0.003 ; independent sample s t-test log(e ) ) ] . IMM patients also had a decreased rate of readmission over a 12-month follow-up period ( 40.8 % vs. 49.3 % ; p = 0.027 ; Fisher 's exact test ) and an increased time to readmission [ 20 days longer ( P = 0.0356 ; log rank test ) ] . A numbers-needed-to-treat calculation indicated that for approximately every 12 patients receiving the IMM service , one readmission to hospital , within 12 months of discharge , would be prevented . The new service was welcomed by cognate health care professionals . CONCLUSION The IMM service proved very effective and can be used as a template to support the implementation of comprehensive pharmaceutical care as a routine service across Northern Irel and and beyond WHAT IS KNOWN AND OBJECTIVE Studies have shown that comprehensive interventions by pharmacists can improve adherence and persistence to osteoporosis therapy , but the association between adherence and bone turnover markers ( BTMs ) has never been studied . Therefore , the aim of this study was to evaluate the effects of pharmaceutical care on medication adherence ( and its effects on BTMs ) , as well as persistence of postmenopausal osteoporotic women to prescribed bisphosphonates . METHODS A r and omized controlled trial was conducted from 2005 to 2009 in the University Malaya Medical Centre , Malaysia . INCLUSION CRITERIA postmenopausal osteoporotic women diagnosed with osteoporosis with a T-score ≤ -2·5 or who had a low-trauma fracture and prescribed weekly alendronate/risedronate . Intervention participants received counselling on osteoporosis , risk factors , lifestyle modifications , goals of therapy , side effects and the importance of adherence . Adherence was assessed at months 3 , 6 and 12 , and persistence at month 12 . Feedback on BTMs was provided at months 4 and 7 . The control group received no counselling . Two BTMs were used : serum C-terminal cross-linking telopeptide of type I collagen ( CTX-I ) and serum osteocalcin ( OC ) . MAIN OUTCOMES MEASURED medication adherence , BTMs and persistence . RESULTS AND DISCUSSION Intervention participants who received pharmaceutical care reported significantly higher medication adherence at 6 ( P = 0·015 ) and 12 months ( P = 0·047 ) compared with the control group ; but this effect was not shown by the BTMs . This is probably due to the long effect of bisphosphonates in bone . A significant difference was found between serum CTX-I and OC in identifying non-responders to anti-resorptive therapy ( P < 0·001 ) , indicating the usefulness of BTMs as an objective marker . However , pharmaceutical care did not affect persistence to osteoporosis therapy within a 1-year period [ log rank ( Mantel-Cox ) χ² = 0·496 , P = 0·481 ] . The proportion of participants who were persistent with bisphosphonate therapy after 12 months was 89·8 % and 87·0 % in the control and intervention group respectively . WHAT IS NEW AND CONCLUSION The provision of pharmaceutical care improved medication adherence but not persistence . BTMs were not appropriate objective measures for assessing adherence to weekly bisphosphonates but were useful for identifying non-responders to treatment within 3 - 6 months , much earlier than using bone mineral density . The study indicates that pharmacists have a role in improving medication adherence , but its long-term effect on persistence warrants further studies with longer duration Objective To assess the impact of an asthma educational program provided by a nurse combined with asthma counseling provided by a pharmacist on asthma knowledge , quality of life and clinical outcomes in Taiwanese patients with asthma . Setting All patients were recruited from Pulmonary Medicine outpatient clinic , the Tri-Service General Hospital , Taipei , Taiwan . Asthma education was given in three one-hour sessions offered during monthly clinic visits . Method A total of 91 asthma patients were r and omly assigned to a nurse-administered education program ( Group 1 ) , the education program with additional pharmacist counseling ( Group 2 ) , or a control group receiving routine care only ( control ) . Three question naires were used for assessment at months 0 , 3 and 6 . Outcomes were compared between groups to determine efficacy . Main Outcome Measure Asthma knowledge , health-related quality of life , and medication adherence were measured at baseline and 3 and 6 months after enrollment . Results A total of 104 patients were enrolled ; 91 completed the study . Knowledge scores of patients in Groups 1 and 2 increased significantly compared to control group . Both intervention groups showed significant increases in knowledge scores with longer follow-up . Group 2 showed a significant improvement in clinical symptoms between baseline ( month 0 ) and month 6 ( 4.99 vs. 4.21 , P = 0.008 ) . No significant differences in medication adherence were seen among groups . Conclusion Regular nurse-administered asthma education with additional pharmacist counseling improves asthma knowledge and clinical symptoms in asthma patients OBJECTIVES To test the feasibility of implementing ask-advise-refer ( AAR ) tobacco cessation counseling approach in community chain pharmacies serving low socioeconomic areas and to assess the effectiveness of a multimodal intervention on short-term implementation of AAR . DESIGN R and omized controlled trial . SETTING South- central Wisconsin from July 2008 through March 2009 . PARTICIPANTS Pharmacists and technicians from 16 community chain pharmacies . INTERVENTION Training to implement AAR , workflow integration recommendations , tobacco cessation poster to create awareness , and a support visit . MAIN OUTCOME MEASURES Number of pharmacy patrons asked about tobacco use , number of tobacco users advised to quit , number of tobacco users enrolled in the quit line , and number of quit line cards given . RESULTS As hypothesized , the multimodal intervention significantly predicted the number of patrons asked to quit ( estimate 4.84 , incidence rate ratio 127.2 , P < 0.001 ) , number of tobacco users advised to quit ( 2.12 , 8.33 , P < 0.01 ) , number of tobacco users enrolled in the quit line ( 2.31 , 10.13 , P < 0.001 ) , and number of quit line cards given ( 1.04 , 2.82 , P < 0.05 ) . CONCLUSION This trial demonstrates the feasibility of implementing AAR in routine community pharmacy practice . This trial also supports the short-term effectiveness of the multimodal intervention in facilitating AAR in partnership with other public health systems . More research is needed to evaluate the generalizability , effectiveness , and sustainability of AAR , including factors influencing adoption and the impact on cessation STUDY OBJECTIVE To implement and assess a community-based pharmaceutical care program for patients with asthma . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Community pharmacies ( 11 control , 11 intervention ) in Malta . PATIENTS Community-dwelling patients with asthma . INTERVENTIONS A comprehensive asthma education and monitoring program was implemented . Intervention patients received verbal counseling , an educational video , an information leaflet , and subsequent monitoring with reinforcement ; control patients received routine dispensing services . MEASUREMENTS AND MAIN RESULTS Parameters assessed at baseline and at 4 , 8 , and 12 months were health-related quality of life , peak expiratory flow ( PEF ) , inhaler technique , compliance with therapy , hospitalization rates , days lost from work , asthma symptoms , and patient satisfaction . Health-related quality of life of the intervention patients improved at 12 months ( p=0.044 ) . In the same time period , PEF significantly decreased in control patients compared with intervention patients ( p=0.009 ) whereas inhaler technique improved in the intervention group ( p=0.021 ) . There were significantly fewer self-reported hospitalizations in intervention patients . CONCLUSIONS A community-based pharmaceutical care program was appreciated by the participants and had a positive impact on the vitality of patients with asthma , inhaler technique , and PEE This was a prospect i ve , cluster r and omized controlled trial in patients with uncontrolled hypertension aged 21 to 85 years ( mean , 61 years ) . Pharmacists made recommendations to physicians for patients in the intervention clinics ( n=101 ) but not patients in the control clinics ( n=78 ) . The mean adjusted difference in systolic blood pressure ( BP ) between the control and intervention groups was 8.7 mm Hg ( 95 % confidence interval [ CI ] , 4.4 - 12.9 ) , while the difference in diastolic BP was 5.4 mm Hg ( CI , 2.8 - 8.0 ) at 9 months . The 24-hour BP levels showed similar effects , with a mean systolic BP level that was 8.8 mm Hg lower ( CI , 5.0 - 12.6 ) and a mean diastolic BP level that was 4.6 mm Hg ( CI , 2.4 - 6.8 ) lower in the intervention group . BP was controlled in 89.1 % of patients in the intervention group and 52.9 % in the control group ( adjusted odds ratio , 8.9 ; CI , 3.8 - 20.7 ; P<.001 ) . Physician/pharmacist collaboration achieved significantly better mean BP values and overall BP control rates , primarily by intensification of medication therapy and improving patient adherence OBJECTIVE To evaluate treatment compliance and use of inhaled medications of patients with asthma receiving complementary pharmaceutical care . METHODS A controlled prospect i ve parallel study involving a study group and a control group . We selected 60 patients with persistent asthma and using metered-dose inhalers ( MDIs ) , dry powder inhalers ( DPIs ) or both . The patients were evaluated three times over 60 days . Instructions were provided to the patients in the study group at all visits but only at the first visit to those in the control group . The patients using < 80 % or > 120 % of the total number of prescribed doses were classified as noncompliant . The inhalation technique was quantified by a scoring system . A satisfactory technique was defined as a score higher than 7 ( maximum , 9 ) for MDIs and higher than 4 ( maximum , 5 ) for DPIs . RESULTS The final study sample comprised 28 study group patients and 27 control group patients , of whom 18 ( 64.3 % ) and 20 ( 74.7 % ) , respectively , were considered treatment compliant . From the first to the third visits , there were increases , in the study and control groups , in the median MDI-use score ( from 3 [ range , 0 - 5 ] to 8 [ range , 8 - 9 ] ; p < 0.001 ; and from 5 [ range , 2 - 6 ] to 7 [ range , 6 - 8 ] ) , as well as in the median DPI-use score ( from 3 [ range , 2 - 4 ] to 5 [ range , 4 - 5 ] and from 3 [ range , 2 - 4 ] to 4 [ range , 3 - 5 ] ) . CONCLUSIONS The counseling provided by the pharmacist to the patient was important to assist in the implementation of the appropriate inhalation technique , especially for MDI use Three programs with different levels of pharmacist intervention design ed to prevent drug-nutrient interactions ( DNIs ) were studied . Six drugs were selected for the study on the basis of their potential for involvement in significant DNIs and the hospital 's drug-use profile . During a two-week control phase , the existing pharmacy system , in which no patient-specific information on DNIs is provided , was assessed . During the next four weeks , patients were r and omly assigned to intervention 1 , placement of a brightly colored label in the medication drawer and on the cover of the nursing medication card flip-chart , or to intervention 2 , placement of the labels plus a five-minute structured patient-counseling session . Occurrence of DNIs and nurses ' and patients ' knowledge of DNIs were assessed . A DNI was defined as potentially altered drug absorption due to inappropriate timing or administration of a drug in relation to food . The occurrence of DNIs decreased significantly under the label system ( from 24 % to 19 % ) and under the combined label-counseling system ( to 16 % ) . However , the frequency of DNIs did not differ significantly between the two intervention groups . Patients ' and nurses ' knowledge of DNIs improved as a result of the interventions . The frequency of DNIs decreased when labels were used to alert nurses to proper medication timing Objective : To assess the impact of pharmacist counseling on empowering people with diabetes to better self-care . Introduction : Community-based pharmacists can play a key role in educating and empowering people in such programs . Methods : A r and omized trial compared the effects of pharmacist counseling ( intervention group ) with printed material s ( control group ) in diabetic beneficiaries of several employer-based health care plans . All participants also received waiver of out-of-pocket expenses for diabetic-related medications and supplies . Clinical , humanistic , and cl aim outcomes were evaluated at baseline and at 1 year follow-up . Results : Sixty-seven beneficiaries participated in this study . The 0.50 % decrease from baseline in glycosylated hemoglobin ( A1c ) was statistically significant ( P = .0008 ) in the intervention group and the difference between the groups approached statistical significance ( P = .076 ) . Beneficiaries in both groups had greater cl aim costs for diabetic-related medications and supplies during the study year . Both groups also improved in ability to manage their diabetes with the counseling group showing a significantly better underst and ing of diabetes ( P = .0024 ) . Conclusion : There was a trend toward improvement in A1c in patients counseled by pharmacist with an increased utilization of diabetes-related medications and supplies . Counseling also improved diabetes knowledge and empowered patients to better diabetes management 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 1 . Cardiologists and pharmacists at the University Hospital of Wales collaborated to write 20 individual leaflets incorporating guidelines for a range of drugs used in the treatment of cardiology patients . The Plain English Campaign advised on the intelligibility and presentation of the information . 2 . One hundred and twenty-five patients from the Regional Cardiology Unit , University Hospital of Wales were r and omly allocated to receive usual verbal counselling about their drug treatment with or without an individualised drug information wallet . Two weeks after discharge from hospital patients completed a postal question naire to determine their satisfaction with the information about their drug treatment and their underst and ing of it . Forty-nine question naires were returned from the leaflet group and 52 from the control group . 3 . The provision of written guidelines result ed in significant improvements in patients ' satisfaction with their drug treatment ( chi 2 = 33.3 , P less than 0.001 ) and their underst and ing of it ( P less than 0.001 , Mann-Whitney test ) . Overall , patients who received leaflets were more likely to be aware of the potential side effects of their drugs but less likely to be apprehensive about them . Succinct guidelines concerning drug therapy can be assimilated by cardiology patients and provide them with a permanent record for future reference AIMS To evaluate whether a structured community pharmacy-based smoking cessation programme ( the PAS model ) would give rise to a higher smoking cessation rate compared with ad hoc advice from pharmacists . DESIGN A r and omized controlled trial comparing a structured intervention with usual care . SETTING One hundred pharmacists working in community pharmacies in N. Irel and and 24 in London took part in the study and were each asked to enroll 12 smokers ; 44 % of pharmacists who were trained managed to recruit one or more smokers during the recruitment period of approximately 1 year . PARTICIPANTS A total of 484 smokers were enrolled by the pharmacists and individually r and omized into the PAS intervention group ( N = 265 ) or the control group ( N = 219 ) . INTERVENTION The PAS intervention involved a structured counselling programme , an information leaflet and a follow-up weekly for the first 4 weeks then monthly as needed . MEASUREMENTS The primary outcome measure of this study was self-reported smoking cessation for 12 months with cotinine validation at the 12-month follow-up . FINDINGS Of smokers in the PAS group , 14.3 % ( 38 ) were abstinent up to 12 months compared with 2.7 % ( 6 ) in the control group ( p < 0.001 for the difference ) . CONCLUSION The community pharmacy-based PAS smoking cessation service can be an effective method of helping people stop smoking when delivered by pharmacists willing to adopt this approach OBJECTIVE To evaluate the effects of providing a unique telephone-based pharmaceutical care program to a sample of patients enrolled at a university pain clinic in Philadelphia , Pa. We hypothesized that in comparison to routine pharmaceutical care , the telephone-based pharmaceutical care program would have a positive impact on delivery of medication , quality of life , and overall satisfaction with the pain clinic program . PATIENTS One hundred seven pain clinic patients were r and omly assigned to the control and intervention groups . Seventy-four patients ( control group , n = 36 ; intervention group , n = 38 ) met inclusion criteria . METHOD The control group continued to receive care and prescription services through the same means as prior to the study . There were 2 components to the pharmaceutical care program offered to the intervention group . The first component consisted of a palliative care pharmacy company , PainRxperts , providing specialized prescription services tailored to the needs of a pain medicine clinical practice . The second component involved the palliative-trained pharmacist 's proactive monitoring of patient pharmacotherapy for potential or actual drug related problems ( DRPs ) . RESULTS Intervention patients perceived that they had better access to medication , more efficient processing of prescriptions , and fewer stigmatizing experiences . They also endorsed pharmacists ' behavioral interventions such as medication counseling , availability to answer medication-related questions , and non-judgmental attitudes when managing opioid prescriptions . CONCLUSION This study suggests that the palliative-trained pharmacist can play an important collaborative role in managing chronic pain . Application of the pharmaceutical care model in pain medicine centers can improve satisfaction and remove some of the barriers to good pharmaceutical care facing patients with chronic pain Background : Despite the high prevalence of headache and migraine in the general population , many people do not receive adequate medical attention and treatment . Objective : To evaluate the effects of pharmaceutical care ( defined as intensified structured counseling between patient and pharmacist , including the use of drug data bases ) , for patients with headache or migraine , on both clinical and psychological endpoints . Methods : A prospect i ve , r and omized , controlled intervention study was conducted using pharmacies in Northern Germany . A total of 112 pharmacies ( 26 % of all pharmacies in the study region ) recruited 410 patients with headaches . Pharmacies were r and omly assigned to an intervention or control group . Patients were interviewed by telephone prior to the intervention and again after 4 months . Primary endpoints were number of days with headache , number and severity of headaches , self-efficacy , and the patients ' perceptions of their health-related quality of life . Results : Each pharmacy treated an average of 4.6 patients ( total time effort 9 h ) . The intervention group consisted of 201 patients who received pharmaceutical care , whereas the control group comprised 209 patients who received st and ard counseling . In both groups , the number of headache attacks and intensity of pain in treated headache attacks did not change significantly between the first and second interviews . However , a statistically significant improvement in mental health and self-efficacy was shown in the intervention group . Intensity of pain in untreated headache attacks and the number of days with headache decreased in both groups . Most participants described this intervention as helpful and effective and 90 % reported that they would recommend pharmaceutical care to other patients with headache . Conclusions : A short-term pharmaceutical care intervention improved patients ' mental health and self-efficacy , although it did not significantly change the number and severity of headaches . The increase in self-efficacy and mental health associated with pharmaceutical care may be instrumental in improving long-term pharmacotherapy of patients with migraine and headache . To fully assess the effects of pharmaceutical care , a longer study may be required Background : Non‐compliance with immunosuppressive medications may result in allograft rejection and is regarded as an important impediment to post‐transplant care . This r and omized , controlled trial evaluates the impact of clinical pharmacy services on renal transplant patients ’ compliance with immunosuppressive agents . Methods : Patients who received a renal transplant at the Medical College of Georgia from February 1997 through January 1999 were r and omized in the intervention or control group provided they met study criteria . In addition to routine clinic services at each clinic visit , patients in the intervention group received clinical pharmacy services , which included medication histories and review of patients ’ medications with an emphasis on optimizing medication therapy to achieve desired outcomes and minimizing adverse medication events . The clinical pharmacist also provided recommendations to the nephrologists with the goal of achieving desired outcomes . To promote medication compliance by using compliance enhancement strategies , the clinical pharmacist counseled patients concerning their medication therapy and instructed them how to properly take their medications . Patients in the control group received the same routine clinic services as the intervention group except that they did not have any clinical pharmacist interaction . Compliance rate ( CR ) was calculated and patient 's compliance status was determined from the CR . The CR , the fraction of patients remaining compliant for each month , and the mean time patients were compliant were compared between groups . Whether there was a difference in the frequency of patients achieving ‘ target ’ immunosuppressive levels in the control and study groups was evaluated . Results : The mean CR for patients who had clinical pharmacist intervention ( n=12 ) was statistically higher than the control group 's ( n=12 ) mean CR ( p<0.001 ) . During the 12‐month post‐transplant study period , patients in the intervention group had a longer duration of compliance than patients in the control group ( p<0.05 ) . Additionally , patients who had clinical pharmacy services had a greater achievement of ‘ target ’ levels than patients who did not receive these services ( p<0.05 ) . Conclusions : Patients who received clinical pharmacy services with traditional patient care services had better compliance with immunosuppressants than patients who only received traditional patient care services . Results of this study suggest a multidisciplinary team that includes a clinical pharmacist as part of the care for post‐transplant patients is beneficial for enhancing medication compliance RATIONALE Care coordination has shown inconsistent results as a mechanism to reduce hospital readmission and postdischarge emergency department ( ED ) visit rates . OBJECTIVE To assess the impact of a supplemental care bundle targeting high-risk elderly in patients implemented by hospital-based staff compared to usual care on a composite outcome of hospital readmission and /or ED visitation at 30 and 60 days following discharge . PATIENTS / METHODS R and omized controlled pilot study in 41 medical in patients predisposed to unplanned readmission or postdischarge ED visitation , conducted at Baylor University Medical Center . The intervention group care bundle consisted of medication counseling/reconciliation by a clinical pharmacist ( CP ) , condition specific education/enhanced discharge planning by a care coordinator ( CC ) , and phone follow-up . RESULTS Groups had similar baseline characteristics . Intervention group readmission/ED visit rates were reduced at 30 days compared to the control group ( 10.0 % versus 38.1 % , P = 0.04 ) , but not at 60 days ( 30.0 % versus 42.9 % , P = 0.52 ) . For those patients who had a readmission/postdischarge ED visit , the time interval to this event was longer in the intervention group compared to usual care ( 36.2 versus 15.7 days , P = 0.05 ) . Study power was insufficient to reliably compare the effects of the intervention on lengths of index hospital stay between groups . CONCLUSIONS A targeted care bundle delivered to high-risk elderly in patients decreased unplanned acute health care utilization up to 30 days following discharge . Dissipation of this effect by 60 days postdischarge defines reasonable expectations for analogous hospital-based educational interventions . Further research is needed regarding the impacts of similar care bundles in larger population s across a variety of inpatient setting Few studies have demonstrated an effect of educational interventions on glycaemic control in persons with Type 2 diabetes longer than 3 - 6 months after baseline . We aim ed to investigate the effectiveness of an experience-based group educational programme 24 months after baseline and to pinpoint mediators that might play a role in achieving desired metabolic outcomes . We conducted a r and omised controlled trial inviting self-referred persons with Type 2 diabetes ( N=77 r and omised ) . The pharmacist-led , year-long intervention was based on participants ' experiences of glucose regulation during the monthly group discussion s. We measured HbA1c at 0 , 6 , 12 , and 24 months and a question naire was administered at baseline and final follow-up . Our findings indicated that participating in the intervention programme significantly decreased HbA1c by 0.4 % at 24 months after baseline . Initial HbA1c , satisfaction with own diabetes-related knowledge , and treatment were found directly related to glycaemic outcomes . The intervention group exercised more in order to lower blood-glucose levels and was also more able to predict current blood-glucose levels before measuring it . Experience-based group education was effective in decreasing participants ' HbA1c 1-year after completed intervention . Early effect of the intervention was followed by relapse after 12 months and a new , significant decrease at 24 months ; this dual course implies that follow-up of educational interventions should involve several consecutive measurements to capture possible late effects . Both biomedical and subjective factors played a role in accounting for the variance of HbA1c at 2-year follow-up after baseline Background The community pharmacist has significant potential to assist in providing health advice aim ed at the improvement outcomes pertaining to weight management , however , up to now , evidence regarding its effectiveness has been inconclusive . In Thail and , community pharmacy involvement in weight management is a novel idea and therefore needs an evaluation of its effectiveness . Objective To examine essential outcomes , comparing the pharmacist ’s interventions with a routine weight management service provided at a primary care unit ( PCU ) . Setting Maha Sarakham province , Thail and . Methods A r and omized controlled trial was design ed involving sixty-six obese patients r and omly assigned to either the control group or the experimental group . Participants in the control group received group counselling from the PCU staff as usual , while those participants in the experimental group received one-on-one advice from a community pharmacist along with the weight loss h and book for self- study . Both groups were followed up and clinical outcomes were monitored four times at weeks 0 , 4 , 8 , and 16 . Eating behaviours and knowledge about overweight and obesity were measured twice , at weeks 0 and 16 . Main outcome measure Clinical outcomes included weight , waist circumference , body mass index , measured by st and ard medical devices . Eating behaviours were measured by the theory of planned behaviour ( TPB ) question naire . Knowledge was measured by a question naire focusing on the subjects ’ level of underst and ing regarding overweight and obesity issues . Results Neither group showed improvement in clinical outcomes . The TPB average sum score significantly increased from baseline in the experimental group in terms of intention to perform healthy dieting behaviour , subjective norm , behavioural beliefs , normative beliefs , and control beliefs . ( P < 0.05 ) In the control group , scores increased significantly from the baseline only for behavioural beliefs . ( P < 0.05 ) Moreover , the knowledge score in experimental group increased significantly from 6.42 ± 1.94 to 8.75 ± 0.68 ( P < 0.05 ) . Conclusion Thai community pharmacists can help to improve both eating behaviour and knowledge about weight and obesity among obese patients . However , since the effect on clinical outcomes is unclear , a long-term study is still needed The Hawai‘i Demonstration to Maintain Independence and Employment was a r and omized controlled trial examining the effect of a participant-driven , multicomponent intervention on 190 employed adults with diabetes , 36 % of whom were Asian and 35 % of whom were Native Hawaiian or Pacific Isl and er . A no treatment concurrent control group was used , and the treatment group was provided an intervention that paired each participant with a life coach and a pharmacist counselor with whom they worked to achieve collaboratively chosen goals . Treatment fidelity data suggest that the intervention was largely implemented as planned . Life coaches and pharmacists performed key program functions with high to moderate adherence . The quality of their adherence to the intervention model ranged from basic to above basic and below basic to above basic for life coaches and pharmacists , respectively . Results of repeated- measures analysis of covariance analyses indicate that the intervention had a significant positive effect on participants ’ diabetes self-efficacy , quality of life , and body mass index but not on hemoglobin A1c levels . Further analyses examining just the treatment group indicate a dosage effect , with body mass index and quality of life outcomes optimized among participants who engaged in a greater number of sessions with life coaches and pharmacists . Implication s of the study findings for practice are discussed PURPOSE Subjects using functional foods with approved health cl aims may be more likely to be non-adherent with prescribed drug therapy . This study aim ed to assess the influence of the use of phytosterol/-stanol-enriched functional foods on adherence to statin therapy among patients initiating treatment . METHODS We used data from the statin intervention research project , a r and omized controlled trial aim ed at improving adherence to statins . In the trial , new statin users were r and omized to receive either usual care or extensive pharmaceutical care consisting of five individual counseling sessions . Customary use of phytosterol/-stanol-enriched products was identified by question naires filled out by all participants . Automated pharmacy-dispensing records were used to assess adherence in terms of discontinuation of therapy and the medication possession ratio . Analyses were performed for the overall population , as well as stratified for receiving pharmaceutical or usual care . RESULTS The use of functional foods enriched with phytosterols/-stanols was not related to discontinuation of statin therapy , neither in the overall population ( overall population adjusted hazard rate ratio ( HR(adj ) ) : 0.80 [ 95%CI : 0.59 - 1.08 ] ) , nor when stratified by r and omization arm ( pharmaceutical care HR(adj ) : 0.77 [ 95%CI : 0.49 - 1.23 ] ) ; usual care HR(adj ) : 0.81 [ 95%CI : 0.54 - 1.21 ] ) . The median medication possession ratio was significantly lower in users of phytosterols/-stanols in the usual care group , but the difference was not clinical ly relevant . CONCLUSIONS Customary use of phytosterol/-stanol-enriched functional foods did not affect adherence to statins in new users that are well informed on the beneficial effects of statin therapy . In daily medical practice , general practitioners and pharmacists should urge subjects not to take phytosterol/-stanol-enriched functional foods as replacement for their prescribed medication Background : Despite the well-known beneficial effects of statins , many patients do not adhere to chronic medication regimens . Objective : To implement and assess the effectiveness of a community pharmacy-based pharmaceutical care program developed to improve patients ' adherence to statin therapy . Methods : An open-label , prospect i ve , r and omized controlled trial was conducted at 26 community pharmacies in the Netherl and s. New users of statins who were aged 18 years or older were r and omly assigned to receive either usual care or a pharmacist intervention . The intervention consisted of 5 individual counseling sessions by a pharmacist during a 1-year period . During these sessions , patients received structured education about the importance of medication adherence , lipid levels were measured , and the association between adherence and lipid levels was discussed . Adherence to statin therapy was assessed as discontinuation rates 6 and 12 months after statin initiation , and as the medication possession ratio ( MPR ) , and compared between the pharmaceutical care and usual care groups . Results : A total of 899 subjects ( 439 in the pharmaceutical care group and 460 in the usual care group ) were evaluable for effectiveness analysis . The pharmaceutical care program result ed in a significantly lower rate of discontinuation within 6 months after initiating therapy versus usual care ( HR 0.66 , 95 % CI 0.46 to 0.96 ) . No significant difference between groups was found in discontinuation at 12 months ( HR 0.84 , 95 % CI 0.65 to 1.10 ) . Median MPR was very high ( > 99 % ) in both groups and did not differ between groups . Conclusions : These results demonstrate the feasibility and effectiveness of a community pharmacy – based pharmaceutical care program to improve medication adherence in new users of statins . Frequent counseling sessions ( every 3 months ) are necessary to maintain the positive effects on discontinuation . Although improvements are modest , the program can be applied easily to a larger population and have a large impact , as the interventions are relatively inexpensive and easy to implement in clinical practice BACKGROUND Nonadherence to cardiovascular medications is a significant public health problem . This r and omized study evaluated the effect on medication adherence of linking hospital and community pharmacists . METHODS Hospitalized patients with coronary artery disease discharged on aspirin , β-blocker , and statin who used a participating pharmacy were r and omized to usual care or intervention . The usual care group received discharge counseling and a letter to the community physician ; the intervention group received enhanced in-hospital counseling , attention to adherence barriers , communication of discharge medications to community pharmacists and physicians , and ongoing assessment of adherence by community pharmacists . The primary end point was self-reported use of aspirin , β-blocker , and statin at 6 months postdischarge ; the secondary end point was a ≥ 75 % proportion of days covered ( PDC ) for β-blocker and statin through 6 months postdischarge . RESULTS Of 143 enrolled patients , 108 ( 76 % ) completed 6-month follow-up , and 115 ( 80 % ) had 6-month refill records . There was no difference between intervention and control groups in self-reported adherence ( 91 % vs 94 % , respectively , P = .50 ) . Using the PDC to determine adherence to β-blockers and statins , there was better adherence in the intervention versus control arm , but the difference was not statistically significant ( 53 % vs 38 % , respectively , P = .11 ) . Adherence to β-blockers was statistically significantly better in intervention versus control ( 71 % vs 49 % , respectively , P = .03 ) . Of 85 patients who self-reported adherence and had refill records , only 42 ( 49 % ) were also adherent by PDC . CONCLUSIONS The trend toward better adherence by refill records with the intervention should encourage further investigation of engaging pharmacists to improve continuity of care AIMS To develop three Vietnamese medicine information leaflets and to evaluate their impact in combination with verbal counselling ( in Vietnamese ) on consumers ' medicine knowledge and satisfaction with the written information received . METHODS Leaflets in Vietnamese were developed for three drug classes : biguanides , calcium channel blockers and HMG-CoA reductase inhibitors . A two-group ( comparison and intervention ) , r and omized , repeated measures design was used . The comparison group ( n = 51 ) received routine verbal counselling in English . The intervention group ( n = 44 ) received verbal and written information in Vietnamese . Australian Vietnamese-speaking consumers were recruited . Data on consumer knowledge and satisfaction were collected from both groups at three time points : baseline ( prior to receiving leaflets and verbal counselling ) , at 1 - 2 weeks ( first postintervention ) and 8 weeks after receiving the information . RESULTS All intervention group respondents were satisfied with the information . Mean medicine knowledge and satisfaction scores increased with time in the intervention group , and were significantly higher than in the comparison group ( knowledge , F = 18.5 , d.f . = 2 , P < 0.0001 ; satisfaction , F = 19.8 , d.f . = 2 , P < 0.0001 ) . The increases observed in the intervention group 's mean knowledge and satisfaction scores at first postintervention were significantly higher compared with baseline for all drug classes . CONCLUSIONS Delivery of written and verbal medicine information in Vietnamese result ed in an increase in consumers ' medicine knowledge and satisfaction with written information . This study highlights the importance of providing information in language s other than English and in consumers ' native tongue to aid in the quality use of medicines PURPOSE : We aim ed to determine to what extent a telephone-based pharmacist intervention would ( a ) be utilized by individuals not attending a traditional cardiac rehabilitation ( CR ) program and ( b ) facilitate adherence to cardiovascular medications . METHODS : We conducted a r and omized , controlled open-label trial among patients eligible for CR in Saskatoon , Canada . Patients were invited to participate in telephone-based CR , regardless of participation in the formal program . Subjects in the intervention group were assessed by the CR pharmacist and received education and counseling on medication adherence . The primary endpoint was adherence to cardiovascular medication assessed by electronic filling records over a minimum of 6 months . Mean adherence was expected to reach 70 % during the followup period . RESULTS : Patient recruitment was halted early because of low enrollment . Of the 95 patients r and omized , 90 % had also registered in the traditional CR program . During the followup period , 129 telephone interactions were performed ( median , 2 calls ) , with every subject taking part in at least 1 interaction . Over the study period , the mean adherence to all recently initiated cardiovascular medications combined was 88.8 % in the intervention group and 89.9 % in the usual care group ( P = .73 ) . CONCLUSIONS : Participation in traditional CR programs does not appear to be influenced by the availability of telephone-based education and support . Furthermore , the high rate of adherence among the control group may suggest that CR programs are attracting “ healthy adherers ” who volunteer for such programs , while missing those with the greatest need for health care system re sources The increased prevalence , morbidity , mortality , and health costs associated with asthma among children suggest the need for accessible asthma education . This study examined the effect of telepharmacy counseling , using interactive compressed video , on metered-dose inhaler ( MDI ) technique and patient satisfaction among adolescents with asthma in rural Arkansas . The telepharmacy counseling provided accessible education regarding MDI technique for adolescents in this study . Twenty percent of the adolescents who participated had never been shown the appropriate use of an MDI . The study used an experimental design with r and om assignment of participants to a telepharmacy counseling group ( n = 15 ) or a control group ( n = 21 ) . Both groups participated in pre-test , post-test , and 2- to 4-week follow-up assessment s for MDI technique and patients satisfaction ( follow-up assessment only ) via interactive compressed video . Results indicated that from pre-test to follow-up the telepharmacy counseling group showed more improvement in MDI technique than participants in the control group ( p < 0.001 ) . There was no significant difference between the telepharmacy counseling group and control group in satisfaction with the instructional sessions ( p = 0.132 ) . Both groups had high levels of satisfaction with the telepharmacy sessions . The study findings demonstrated that patient education provided by pharmacists via interactive compressed video was superior to education provided via written instructions on an inhaler package insert . Interactive compressed video is an effective medium for teaching and improving MDI technique in this rural , adolescent , predominantly African-American population OBJECTIVE To evaluate the effect of a software-supported intervention based on the Transtheoretical Model of Change and motivational interviewing on decreasing discontinuation ( or increasing persistency ) of Avonex ( interferon beta-1a -- Biogen ) , a medication for treatment of multiple sclerosis ( MS ) . DESIGN R and omized controlled experimental design comparison of software-based telephone counseling ( intervention group ) and st and ard care ( control group ) . SETTING United States . PARTICIPANTS 366 patients with MS . INTERVENTION Software-based telephone counseling . MAIN OUTCOME MEASURE Discontinuation of Avonex treatment and movement among stages of the Transtheoretical Model of Change . RESULTS Patients in the software intervention group demonstrated a statistically significantly lower proportion of Avonex treatment ( 1.2 % ) discontinuation than the st and ard care group ( 8.7 % ) . In addition , stage movement away from discontinuation of Avonex ( i.e. , toward continuation of therapy ) was significantly higher in the treatment group . CONCLUSION The Transtheoretical Model of Change constructs and motivational interviewing processes were effectively incorporated into a software-based intervention program , and this significantly decreased the proportion of patients who discontinued treatment of MS with Avonex . The integration of behavioral theory with information systems offers a promising approach for pharmacists and other providers to promote medication persistency BACKGROUND Despite the fact that individuals who smoke are at an increased risk for disease and therefore require frequent visits to pharmacies for medications , most community pharmacies do not integrate tobacco cessation activities into routine practice . OBJECTIVE The objective of this report is to describe the methods and baseline findings for a 2-state r and omized trial evaluating 2 intervention approaches for increasing pharmacy-based referrals to their state 's tobacco quitline . METHODS Participating community pharmacies in Connecticut ( n=32 ) and Washington ( n=32 ) were r and omized to receive either ( 1 ) on-site education with an academic detailer , describing methods for implementing brief interventions with patients and providing referrals to the tobacco quitline or ( 2 ) quitline material s delivered by mail . Both interventions advocated for pharmacy personnel to ask about tobacco use , advise patients who smoke to quit , and refer patients to the tobacco quitline for additional assistance with quitting . Study outcome measures include the number of quitline registrants who are referred by pharmacies ( before and during the intervention period ) , the number of quitline material s distributed to patients , and self-reported behavior of cessation counseling and quitline referrals , assessed using written surveys completed by pharmacy personnel ( pharmacists , technicians ) . RESULTS Pharmacists ( n=124 ) and pharmacy technicians ( n=127 ) , representing 64 participating pharmacies with equal numbers of retail chain and independently owned pharmacies , participated in the study . Most pharmacists ( 67 % ) and half of pharmacy technicians ( 50 % ) indicated that they were not at all familiar with the tobacco quitline . During the baseline ( preintervention ) monitoring period , the quitline registered 120 patients ( 18 in Connecticut and 102 in Washington ) who reported that they heard about the quitline from a pharmacy . CONCLUSION Novel tobacco intervention approaches are needed to capitalize on the community pharmacy 's frequent interface with tobacco users , and these approaches need to be evaluated to estimate their effectiveness . Widespread implementation of brief , yet feasible , pharmacy-based tobacco cessation efforts that generate referrals to a tobacco quitline could have a substantial impact on the prevalence of tobacco use AIMS To investigate how seamless pharmaceutical care could be delivered . METHODS Elderly patients discharged from hospital , to their own home , were r and omized into control and study groups . Control and study group patients received the normal discharge information . The study group were also counselled about their medicines and informed about their pharmaceutical care plan . Copies of the plan were given to the study patients . All patients received a domiciliary visit between 7 and 10 days after discharge . Their current medication was compared with that on discharge and contact was made with the General Practitioner as appropriate . RESULTS Twenty-eight study and 25 control patients with a mean ( s.d . ) age of 77.5 ( 7.3 ) and 77.6 ( 6.1 ) years completed the study . A pharmaceutical domiciliary visit was necessary for 21 ( 75 % ) and 24 ( 96 % ) of the study and control patients respectively . Compliance was better ( P < 0.01 ) in the study group . Unintentional changes to the medication of 31 ( 14 study and 17 control ) patients were found during the visit and after contact with the prescriber all but one prescription was restored to that on discharge . CONCLUSIONS At present it is difficult to ensure seamless pharmaceutical care . A pharmaceutical domiciliary visit may be useful to ensure seamless therapeutic care and thus avoid unnecessary healthcare events and costs after a patient is discharged home This r and omized , controlled trial evaluated the impact of personalized follow-up on compliance rates in high-risk patients receiving combination lipid-lowering therapy over 2 years . A r and om sample of 30 patients 7 - 30 days after cardiac surgery had baseline fasting low-density lipoprotein levels higher than 130 mg/dl . All patients received lovastatin 20 mg/day and colestipol 5 g twice/day . Weekly telephone contact was made with each patient for 12 weeks . Short- and long-term compliance was assessed by pill and packet counts and refill records . Compliance and lipid profile results were significantly better in the intervention group ( p<0.05 ) up to 2 years after the start of therapy than in the control group for all parameters except high-density lipoprotein . However , this effect was not apparent during the first 12 weeks of therapy . Short-term telephone follow-up favorably affected compliance and lipid profile results up to 2 years after start of therapy INTRODUCTION Pharmacists are uniquely positioned within the community to provide smoking cessation counseling to their patients . However , pharmacists experience significant barriers to providing counseling , including limited time , reimbursement , and training in counseling techniques . We tested a computer-driven software system , " Exper_Quit " ( EQ ) , that provided individually tailored interventions to patients who smoke and matching tailored reports for pharmacists to help guide cessation counseling . METHODS A two-phase design was used to recruit an observation-only group ( OBS ; n = 100 ) , followed by participants ( n = 200 ) r and omly assigned to receive either EQ-assisted pharmacist counseling or EQ plus 8 weeks of nicotine transdermal patch ( EQ+ ) . Both treatment groups were scheduled to receive two follow-up counseling calls from pharmacists . RESULTS Most participants in the EQ and EQ+ groups reported receiving counseling from a pharmacist , including follow-up calls , while none of the OBS participants reported speaking with the pharmacist about cessation . At 6 months , fewer OBS participants reported a quit attempt ( 42 % ) compared with EQ ( 76 % ) or EQ+ ( 65 % ) participants ( p < .02 ) . At 6 months , 7-day point-prevalence abstinence was 28 % and 15 % among the EQ+ and EQ groups , respectively , compared with 8 % among OBS participants ( p < .01 ) , and EQ+ participants were twice as likely to be quit than were EQ participants ( p < .01 ) . DISCUSSION A tailored software system can facilitate the delivery of smoking cessation counseling to pharmacy patients . Results suggest that EQ was successful in increasing ( a ) the delivery of cessation counseling , ( b ) quit attempts , and ( c ) quit rates . Pharmacists can play an important role in the effective delivery of smoking cessation counseling AIMS Helicobacter pylori ( H. pylori ) eradication rate varies according to the treatment regimen used and other factors , e.g. antimicrobial resistance and patient compliance . The aim of the present study was to evaluate the influence of patient counselling and follow-up on H. pylori eradication rates and to document the effectiveness of a 1 week eradication regimen consisting of lansoprazole ( 30 mg once daily ) , amoxicillin ( 1 g twice daily ) and clarithromycin ( 500 mg twice daily ) . METHODS Seventy-six dyspeptic patients , who at endoscopy were found to have gastritis , duodenitis or ulceration , and a positive H. pylori urease test , were recruited . Patients were r and omly assigned to an intervention group ( n = 38 ) or a control group ( n = 38 ) . Intervention patients received their medicines via the hospital pharmacy and were counselled ( and followed up ) by a hospital pharmacist . Control patients were given a st and ard advice sheet and referred to their GP who prescribed the same therapy . RESULTS Intervention patients exhibited a statistically significant improvement in the H. pylori eradication rate ( 94.7 % vs 73.7 % ; P = 0.02 ) and compliance ( 92.1 % vs 23.7 ; P < 0.001 ) . Of the 64 H. pylori eradicated patients , 62 were able to eliminate their antisecretory medication compared with only 12 of the H. pylori persistent patients ( P < 0.001 ) . A pharmacoeconomic evaluation indicated that counselling and follow-up reduced the direct costs of eradication by approximately 30 UK pounds per patient . CONCLUSIONS Structured patient counselling and follow-up can have a significant effect on H. pylori eradication rates and should be a routine part of therapy OBJECTIVES To demonstrate that pharmacists working with physicians and other providers in an ambulatory care setting can improve glucose , blood pressure , and lipid control for patients with type 2 diabetes and to report patient adherence to screening and general preventive measures . DESIGN Prospect i ve , r and omized , clinical practice study . SETTING Burlington , MA , between January 2001 and August 2003 . PATIENTS 164 patients patients with type 2 diabetes older than 18 years with glycosylated hemoglobin ( A1C ) greater than 8 % . INTERVENTION Pharmacist-patient clinic visits included obtaining a comprehensive medication review ; performing targeted physical assessment ; ordering laboratory tests ; review ing , modifying , and monitoring patients ' medication therapy and providing detailed counseling on all therapies ; facilitating self-monitoring of blood glucose ; and providing reinforcement of dietary guidelines and exercise . MAIN OUTCOME MEASURE Effect of clinical pharmacists working with physicians in an ambulatory setting on health measures ( e.g. , A1C , blood pressure , cholesterol ) of patients with diabetes . RESULTS Baseline characteristics were similar between the two groups . After 1 year , significant improvements occurred for A1C and low-density lipoprotein ( LDL ) cholesterol in the intervention group compared with the control group ( A1C , 7.7 % vs. 8.4 % ; LDL , 93.7 vs. 105.1 mg/dL ; P < 0.05 ) . Systolic blood pressure improved for all study patients without a difference between the two groups . Diastolic blood pressure improved significantly in the intervention group compared with the control group ( 73.4 mm Hg vs. 77.6 mm Hg , P < 0.05 ) . Significantly more intervention patients were screened for retinopathy , neuropathy , and microalbuminuria than control patients ( P < 0.05 ) . CONCLUSION For all indices measured , this study demonstrated that collaborative diabetes management with a clinical pharmacist can improve overall care The aim of this study was to determine whether improved compliance by intensive medication counselling , given by a pharmacist , to elderly patients with chronic stable heart failure can influence both objective and subjective measures of heart failure . Elderly patients were r and omly allocated to receive a 3-month counselling programme , or no counselling . Measures recorded at the beginning and end of the study included ; submaximal 6-minute exercise tests , visual analogue scores of breathlessness , the Nottingham Health Profile , and clinical signs of heart failure . Compliance was measured by a tablet count and medication knowledge assessed by means of a question naire . There was no significant difference between the groups in their initial level of compliance , medication knowledge or other assessment s. Compliance improved for the counselled group by 32 % ( P < 0.001 ) but remained unchanged for controls . Medication knowledge improved for the counselled group only . The 6-minute exercise test improved by 20 metres from a baseline of 137 m for the counselled group ( P < 0.005 ) but worsened by 22 m for the control group ( P < 0.01 ) . Distance to breathlessness improved for the counselled patients and worsened for controls . In contrast bodyweight , jugular venous pressure and Nottingham Health Profile scores did not change significantly for either group . Peripheral and pulmonary oedema scores improved for the counselled group ( P < 0.01 ) but remained unchanged for controls . A small improvement was seen in the visual analogue scores ( P < 0.05 ) for the counselled group only . Improved compliance due to intensive medication counselling had a small but measurable beneficial effect on objective measures of heart failure . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Although some studies have demonstrated that pharmacist intervention can improve drug therapy among patients with cardiovascular disease ( CVD ) , more evidence derived from r and omized controlled trials ( RCTs ) is needed , including assessment of the effect of community pharmacist interventions in patients with CVD . OBJECTIVE To assess the effectiveness of the Dader Method for pharmaceutical care on achieving therapeutic goals for blood pressure ( BP ) , total cholesterol ( TC ) , and both BP and TC ( BP/TC ) in patients with CVD and /or high or intermediate cardiovascular ( CV ) risk attending community pharmacies in Spain . METHODS Patients aged 25 to 74 years attending community pharmacies with a prescription for at least 1 drug indicated for CVD or CV risk factors were r and omized to 2 groups : an intervention group that received pharmaceutical care , which was provided by specially trained pharmacists working in collaboration with physicians , and a control group that received usual care ( routine dispensing counseling ) and verbal and written counseling regarding CVD prevention . Patients were recruited from December 2005 to September 2006 , and both groups were followed for 8 months . Study outcomes were assessed at baseline and at 16 and 32 weeks after r and omization . The primary outcome measures were the proportions of patients achieving BP , TC , and BP/TC therapeutic goals ( BP lower than 140/90 mm Hg for patients with uncomplicated hypertension and lower than 130/80 mm Hg for patients with diabetes , chronic kidney disease , or history of myocardial infa rct ion or stroke ; TC lower than 200 mg per dL for patients without CVD and lower than 175 mg per dL for patients with CVD ) . Secondary outcomes were mean BP and TC values . BP was assessed manually by the pharmacist after a 10-minute rest in the supine position . This measurement was performed twice for every participant , and the average of the 2 measurements was calculated . TC was measured by the pharmacist during the study visit using the enzymatic dry method . Statistical analyses were performed using 2-tailed McNemar tests , Pearson chi-square tests , and Student 's t-tests ; P < 0.05 was considered statistically significant . RESULTS 714 patients were included in the study ( 356 intervention , 358 control ) , and the mean [ SD ] age was 62.8 [ 8.1 ] years . The 2 groups were similar at baseline in clinical and demographic characteristics , including the proportion of patients at therapeutic goals for BP , TC , and BP/TC . After 8 months of follow-up , there were statistically significant differences in favor of pharmaceutical care in the proportions of patients who achieved therapeutic goals for BP ( 52.5 % vs. 43.0 % , P=0.017 ) , TC ( 56.5 % vs. 44.1 % , P=0.001 ) , and BP/TC ( 37.1 % vs. 21.8 % , P < 0.001 ) . CONCLUSION Compared with usual care plus written education , pharmaceutical care focused on patient evaluation and follow-up in collaboration with physicians improved the achievement of BP , TC , and BP/TC treatment goals in patients with CVD and /or high or intermediate CV risk attending community pharmacies in Spain CONTEXT It is not known whether patient outcomes are enhanced by effective pharmacist-patient interactions . OBJECTIVE To assess the effectiveness of a pharmaceutical care program for patients with asthma or chronic obstructive pulmonary disease ( COPD ) . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted at 36 community drugstores in Indianapolis , Ind. We enrolled 1113 participants with active COPD or asthma from July 1998 to December 1999 . Outcomes were assessed in 947 ( 85.1 % ) participants at 6 months and 898 ( 80.7 % ) at 12 months . INTERVENTIONS The pharmaceutical care program ( n = 447 ) provided pharmacists with recent patient-specific clinical data ( peak expiratory flow rates [ PEFRs ] , emergency department [ ED ] visits , hospitalizations , and medication compliance ) , training , customized patient educational material s , and re sources to facilitate program implementation . The PEFR monitoring control group ( n = 363 ) received a peak flow meter , instructions about its use , and monthly calls to elicit PEFRs . However , PEFR data were not provided to the pharmacist . Patients in the usual care group ( n = 303 ) received neither peak flow meters nor instructions in their use ; during monthly telephone interviews , PEFR rates were not elicited . Pharmacists in both control groups had a training session but received no components of the pharmaceutical care intervention . MAIN OUTCOME MEASURES Peak expiratory flow rates , breathing-related ED or hospital visits , health-related quality of life ( HRQOL ) , medication compliance , and patient satisfaction . RESULTS At 12 months , patients receiving pharmaceutical care had significantly higher peak flow rates than the usual care group ( P = .02 ) but not than PEFR monitoring controls ( P = .28 ) . There were no significant between-group differences in medication compliance or HRQOL . Asthma patients receiving pharmaceutical care had significantly more breathing-related ED or hospital visits than the usual care group ( odds ratio , 2.16 ; 95 % confidence interval , 1.76 - 2.63 ; P<.001 ) . Patients receiving pharmaceutical care were more satisfied with their pharmacist than the usual care group ( P = .03 ) and the PEFR monitoring group ( P = .001 ) and were more satisfied with their health care than the usual care group at 6 months only ( P = .01 ) . Despite ample opportunities to implement the program , pharmacists accessed patient-specific data only about half of the time and documented actions about half of the time that records were accessed . CONCLUSIONS This pharmaceutical care program increased patients ' PEFRs compared with usual care but provided little benefit compared with peak flow monitoring alone . Pharmaceutical care increased patient satisfaction but also increased the amount of breathing-related medical care sought STUDY OBJECTIVE To evaluate whether a simple pharmacist protocol , consisting of patient screening and cardiovascular risk stratification , identification and reminders about uncontrolled risk factors , and drug adherence support , can significantly reduce cardiovascular risk . DESIGN Prospect i ve , r and omized , controlled pilot study . SETTING Large primary care medical clinic in Saskatoon , Saskatchewan , Canada . PATIENTS One hundred seventy-six adult patients ( mean age 60 yrs ) who exhibited a 10-year Framingham risk score of 15 % or greater , or a coronary artery disease risk equivalent ( coronary artery disease , peripheral artery disease , cerebrovascular disease , or diabetes mellitus ) . INTERVENTION Eligible patients initially met with the pharmacist to receive general counselling about cardiovascular disease and were then r and omly assigned to receive ongoing follow-up by the pharmacist ( follow-up group [ 88 patients ] ) or to return to usual care ( single-contact group [ 88 patients ] ) for a minimum of 6 months . MEASUREMENTS AND MAIN RESULTS The primary end point was mean reduction in the 10-year Framingham risk score . Secondary end points included individual modifiable risk factors ( systolic and diastolic blood pressures ; total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol [ HDL ] , and triglyceride levels ; total cholesterol : HDL ratio ; and hemoglobin A(1c ) value ) , as well as statin utilization , initiation , and adherence rates . Baseline characteristics were similar across both groups . Neither the mean reduction in 10-year risk ( -2.68 for the follow-up group and -1.25 for the single-contact group , one-tailed p=0.098 ) nor individual risk factors were significantly different between groups . The proportion of patients exhibiting statin adherence of 80 % or greater did not significantly differ between groups at study end ( 73.1 % [ 57/78 ] and 80.0 % [ 52/65 ] , respectively , p=0.333 ) . However , 85.2 % ( 75/88 ) in the follow-up group continued with statin therapy at the end of the study compared with 67.0 % ( 59/88 ) in the single-contact group ( p=0.005 ) . Statin initiations were more frequent in the follow-up group than in the single-contact group ( 75.0 % [ 30/40 ) vs 48.9 % [ 22/45 ] , p=0.013 ) . CONCLUSION This simple cardiovascular care protocol for nonspecialist pharmacists did not result in a clear improvement to cardiovascular risk reduction success among patients in a primary care medical clinic . The intervention did , however , appear to improve statin utilization Purpose : Diabetes transitional care from the inpatient to outpatient setting is understudied . This study evaluated the effect of inpatient pharmacist discharge counseling on outpatient diabetes medication adherence . Research methods : Prospect i ve , r and omized , controlled study compared pharmacist discharge counseling ( intervention ) with usual patient care ( control ) in 127 patients with established diabetes and an A1C ≥8 % who had a provider and medications filled within the county health system . The primary outcome was diabetes medication adherence rate measured using the prescription of days covered ( PDC ) method . Results : Patients in the intervention , compared with control group , had greater diabetes medication adherence rate 150 days after discharge ( 55.2 % vs 34.8 % ; P = .002 ) , rate of follow-up visits ( 60.5 % vs 43.9 % ; P = .01 ) and reduction in A1C ( −1.97 % vs + 0.114 % ; P = .003 ) . Being in the intervention group and having greater adherence with follow-up visits correlated independently with lower follow-up A1C . Conclusion : Transitional care in the form of inpatient education geared to improve self-management after hospital discharge . This may serve as a paradigm to improve outpatient adherence rate with medications , follow-up visits , and A1C reduction OBJECTIVE To determine whether pharmaceutical care provided by a pharmacist-managed hypertension clinic results in better treatment outcomes when compared with traditional health care from a primary care physician . DESIGN Prospect i ve , controlled study SETTING Veterans Affairs Medical Center , Philadelphia , Pennsylvania . PATIENTS Fifty six patients with essential hypertension ; 27 were r and omly assigned to the intervention group and 29 to the control group . INTERVENTION Patients in the intervention group were scheduled monthly to meet with a clinical pharmacist who made appropriate changes in prescribed drugs , adjusted dosages , and provided drug counseling in accordance with the hypertension guidelines in the sixth report of the Joint National Committee on the Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) . Patients in the control group received st and ard care from their physicians . The study period was 6 months . MEASUREMENTS AND MAIN RESULTS Treatment outcomes were measured by changes in compliance , blood pressure , and patient satisfaction . The Short Form-36 health survey and a patient satisfaction survey were used to measure changes in patient satisfaction , and a compliance evaluation survey measured compliance . Twenty-one ( 81 % ) patients in the intervention group attained their blood pressure goal of below 140/90 mm Hg at the completion of the study versus only eight ( 30 % ) in the control group ( p < 0.0001 ) . Of 11 patients with diabetes in the intervention group , 10 ( 91 % ) attained their blood pressure goal ( < 130/80 mm Hg ) versus only two ( 12 % ) of 16 patients with diabetes in the control group ( p < 0.0001 ) . No significant differences in patient satisfaction or compliance were reported between the intervention and control groups . CONCLUSIONS Pharmaceutical care improves blood pressure control and results in more patients with hypertension reaching their blood pressure goal AIMS The use of medication and information discharge summaries ( MIDS ) has become a st and ard procedure in many hospitals . We have evaluated if these summaries , together with in-patient pharmaceutical counselling backed up with a simple medicine reminder card , may help with the delivery of seamless pharmaceutical care . METHODS Elderly patients prescribed more than four items discharged to their own home received the st and ard discharge policy including a recently introduced MIDS and medicine reminder card . Each patient 's GP was sent a copy on discharge . Pre-discharge a pharmacist counselled study patients about their medicines and compliance . A research pharmacist visited patients in their home approximately 2 - 3 weeks and at 3 months post-discharge to determine their drug knowledge , compliance , home medicine stocks and any healthcare related events . RESULTS Forty-three study and 40 control patients completed both visits . Their mean ( s.d . ) ages were 80.2 ( 5,7 ) and 81.1 ( 5,8 ) years and they were prescribed 7.1 ( 1.8 ) and 7.1 ( 2.3 ) items , respectively . At visit 1 knowledge ( P < 0.01 ) and compliance ( P < 0.001 ) was better in the study group . At visit 2 compliance had improved in the study group ( P < 0.001 ) . Unplanned visits to the GP and readmission to hospital amongst the study group were 19 and 5 , respectively , which were both significantly less ( P < 0.05 ) than 27 and 13 in the control group . At visit 2 for the study group the 24 unplanned GP visits and three re-admissions were significantly ( P < 0.05 ) less than the respective 32 and 15 in the control group . At visit 1 , two study group patients had altered their own medication compared with 10 control patients . At visit 2 these reduced to 0 and 4 , respectively . CONCLUSIONS In-patient pharmaceutical counselling , linked to a medication and information discharge summary and a medicine reminder card , contributed to better drug knowledge and compliance together with reduced unplanned visits to the doctor and re-admissions . A pharmaceutical domiciliary visit consoli date d the improved healthcare outcomes PURPOSE To assess the efficacy of a pharmacist-led , primary care-based , disease management program to improve cardiovascular risk factors and glycated hemoglobin ( A(1C ) ) levels in vulnerable patients with poorly controlled diabetes . METHODS A r and omized controlled trial of 217 patients with type 2 diabetes and poor glycemic control ( A(1C ) level > or=8.0 % ) was conducted at an academic general medicine practice from February 2001 to April 2003 . Intervention patients received intensive management from clinical pharmacists , as well as from a diabetes care coordinator who provided diabetes education , applied algorithms for managing glucose control and decreasing cardiovascular risk factors , and addressed barriers to care . Control patients received a one-time management session from a pharmacist followed by usual care from their primary care provider . Outcomes were recorded at baseline and at 6 and 12 months . Primary outcomes included blood pressure , A(1C ) level , cholesterol level , and aspirin use . Secondary outcomes included diabetes knowledge , satisfaction , use of clinical services , and adverse events . RESULTS For the 194 patients ( 89 % ) with 12-month data , the intervention group had significantly greater improvement than did the control group for systolic blood pressure ( -9 mm Hg ; 95 % confidence interval [ CI ] : -16 to -3 mm Hg ) and A(1C ) level ( -0.8 % ; 95 % CI : -1.7 % to 0 % ) . Change in total cholesterol level was not significant . At 12 months , aspirin use was 91 % in the intervention group versus 58 % among controls ( P < 0.0001 ) . Intervention patients had greater improvements in diabetes knowledge and satisfaction than did control patients . There were no significant differences in use of clinical services or adverse events . CONCLUSION Our comprehensive disease management program reduced cardiovascular risk factors and A(1C ) levels among vulnerable patients with type 2 diabetes and poor glycemic control OBJECTIVE To explore the impact of telephone-based education and monitoring by community pharmacists on multiple outcomes of pharmacist-patient collaboration . DESIGN A r and omized , controlled , unblinded , mixed experimental design . SETTING Eight Wisconsin community pharmacies within a large managed care organization . PATIENTS A total of 63 patients presenting new antidepressant prescriptions to their community pharmacies . INTERVENTIONS Patients were r and omized to receive either three monthly telephone calls from pharmacists providing pharmacist-guided education and monitoring ( PGEM ) or usual pharmacist 's care . Usual care is defined as that education and monitoring which pharmacists may typically provide patients at the study pharmacies . MAIN OUTCOME MEASURES Patient 's frequency of feedback with the pharmacist , antidepressant knowledge , antidepressant beliefs , antidepressant adherence at 3 and 6 months , improvement in depression symptoms , and orientation toward treatment progress . RESULTS Of the 60 patients who completed the study , 28 received PGEM and 32 received usual pharmacist 's care . Results showed that PGEM had a significant and positive effect on patient feedback , knowledge , medication beliefs , and perceptions of progress . There were no significant group differences in patient adherence or symptoms at 3 months ; however , PGEM patients who completed the protocol missed fewer doses than did the usual care group at 6 months ( P < or = .05 ) . CONCLUSION Antidepressant telemonitoring by community pharmacists can significantly and positively affect patient feedback and collaboration with pharmacists . Longer-term studies with larger sample s are needed to assess the generalizability of findings . Future research also needs to explore additional ways to improve clinical outcomes The impacts of two models of pharmacist consultation on patient satisfaction with pharmaceutical services relative to a control model were studied . Patients in the r and om-assignment and areawide studies of the Kaiser Permanente/USC Patient Consultation Study were asked to rate their satisfaction with six aspects of the service they received at the pharmacy . The patients were receiving pharmaceutical services under the Kaiser Permanente ( KP ) model of consultation , a state-m and ated model , or a control model . They were assigned to risk categories according to their pattern of prescription drug use . Differences in satisfaction among the three consultation models for all patients and for each risk group and correlations between satisfaction items were determined . The KP and state models of consultation were associated with better satisfaction than the control model on five of the six satisfaction items . In the high-risk patient groups , the KP and state models were associated with higher levels of satisfaction than the control model . In the low-risk group , the state model was associated with higher levels of satisfaction than the control model ; results for low-risk patients assigned to the KP model were inconsistent between the r and om-assignment study and the areawide study . Overall satisfaction appeared to be a suboptimal measure of satisfaction with consultation . Overall satisfaction was more closely related to satisfaction with waiting time and with whether the pharmacy staff was helpful and caring than with the three items reflecting satisfaction with the content of the consultation . Patients were more satisfied under the state model of pharmacist consultation or the KP model of consultation , which result ed in more-intensive counseling for fewer patients , than under a control model BACKGROUND The aim of the trial was to evaluate the effectiveness of a program of cooperation between physician and pharmacist to reduce cardiovascular risk factors in patients with mild to moderate hypertension by promoting better blood pressure ( BP ) control , appropriate changes in antihypertensive medications , and beneficial changes in lifestyle . METHODS The 132 subjects in this r and omized , controlled trial were in the age range of 40 - 79 years . The inclusion criteria were : systolic BP ( SBP ) ranging from 140 - 179 mm Hg and /or diastolic BP ( DBP ) ranging from 90 - 99 mm Hg and treatment-naive ( untreated for hypertension ) ; or on a regimen of medication for hypertension . Of these 132 subjects , 124 ( 94 % ) were already receiving treatment with antihypertensive medications . Equal numbers of subjects were r and omly assigned to one of two groups : a physician-pharmacist intervention group ( n = 66 ) and a control group ( n = 66 ) . RESULTS The 6-month follow-up rate was 97 % in both groups . At 6 months , the mean decrease in SBP/DBP , as measured at home in the morning , was 2.9/3.3 mm Hg in the intervention group relative to baseline ( P = 0.02 and P < 0.0001 for SBP and DBP , respectively ) . The mean decrease in home morning SBP in the intervention group was not significantly greater than in the control group . However , the DBP decline was significantly greater in the intervention than control groups , which showed a mean decrease of 2.8 mm Hg ( confidence interval : -5.5 to -0.1 ; P = 0.04 ) . The percentage of patients in whom control of home morning BP was achieved was 53 % in the intervention group and 47 % in the control group ( P = 0.40 ) . A higher percentage of patients in the intervention group , relative to the control group , were able to reduce the use of antihypertensive medications ( 31 vs. 8 % , P < 0.0001 ) , and fewer patients in this group required additional medications or increases in dosage relative to the controls ( 11 vs. 28 % , P = 0.03 ) . Patients of the intervention group were more likely to show reduction in body mass index and sodium intake and to stop smoking , as compared with the control group . CONCLUSIONS A program of cooperation between physician and pharmacist was successful in reducing cardiovascular risk factors in patients with mild to moderate hypertension by promoting better blood pressure ( BP ) control , appropriate changes in antihypertensive medications , and beneficial changes in lifestyle Objective To evaluate clinical pharmacist-led pain-medication education in patients with cancer . Methods A controlled study was conducted prospect ively at six tertiary hospitals in China . In- patients with cancer were r and omized to receive conventional treatment plus medication education or no education ( controls ) . Education consisted of access to information booklets and eight 30-min face-to-face counselling sessions given by clinical pharmacists over 4 weeks . Patients completed pain- and analgesic-knowledge assessment s and a Brief Pain Inventory , pre- and post- study . Results A total of 123 and 114 patients in the education and control groups , respectively , completed follow-up . At the end of the study , patient knowledge regarding cancer pain and pain control was significantly increased in both groups ; pain and analgesic knowledge scores were significantly higher in the education group compared with controls . In the control group , the increase in total pain-related knowledge was significantly greater in analgesic-naïve patients compared with those who were using/had used analgesics . Pain intensity scores and pain interference of daily activities were significantly reduced in the education group compared with controls . Conclusions Clinical pharmacist-led medication education result ed in improved pain control in patients with cancer OBJECTIVE To assess patients ' opinion toward receiving written or specialized verbal pharmacists ' interventions and to determine the effect of these interventions on patients ' medication knowledge . METHODS 150 newly diagnosed patients with unipolar depression and initiated with a single antidepressant were r and omized into 3 groups : control , leaflet and counselling , and interviewed at initiation and after 6 - 8 weeks of treatment at the outpatient department of the Psychiatric Hospital in Kuwait . RESULTS 50 % of respondents asserted that clinicians did not give them sufficient information while 90 % favoured the idea of receiving further information about therapy . Forty seven percent of participants failed to return for the second follow-up appointment . The drop-out rate was 66 % in the control , 42 % in the Leaflet and only 34 % in the counselling groups ( P=0.004 ) . A broad support for receiving leaflets and drug counselling ( 97 % ) was found among attendees . Moreover , 94 % of the counselling and 79 % of the leaflets group affirmed that they received adequate information compared to 47 % of the control ( P=0.001 ) . Counselling was found to be significantly associated with a much higher recall of medicine name ( OR=9.6 , P=0.01 ) , how to manage missed doses ( OR=8.9 , P=0.007 ) , and correct use of medication ( OR=31.3 , P<0.001 ) . Leaflet use was less strongly associated than counselling and was statistically significant for recall regarding correct use of medication ( OR=8.4 , P=0.009 ) . CONCLUSION Pharmacists in a psychiatric institution can play an important role in satisfying patient dem and s for specialized information about their medications . Patients with depression appear very eager to receive additional drug information with modest difference between the written and the verbal counselling interventions . Patients looked at the two interventions in a very positive manner and no difference was observed between patients in the leaflets and in the counselling group with regards to how helpful , sufficient , supportive and reassuring was the educational material . However , both interventions were more informative than the control in conveying elemental drug information to patients . PRACTICE IMPLICATION S In contrast with the lack of enthusiasm that some clinicians express , the affirmativeness that was expressed by patients towards receiving written or verbal specialized educational interventions by pharmacists may support the psychiatric hospital pharmacists ' st and s in providing them for all patients which may aid in improving patients compliance and probably treatment outcome OBJECTIVE To evaluate the use of patient self-completion concordance forms and to determine the effect of patient counselling by using concordance forms on adherence to chronic medication . METHODS Patients with a prescription for new chronic treatment were r and omised in an intervention or control group . The intervention group received a concordance form to fill in at home and to discuss during a consultation 2 weeks later in the pharmacy . The control group received the usual information and instruction on how to use the medicine . Afterwards , all patients were asked to fill in a question naire about their use of medicines and contact with the pharmacy employees . Adherence to the medicine was determined using rates of prescription refills after 6 months of use . RESULTS The question naires showed that patients were satisfied about the concordance model . After 6 months of use , 79 % of the patients from both intervention and control group were defined as adherent . CONCLUSIONS There was no significant difference found in adherence between intervention and control group . PRACTICE IMPLICATION S Use five selected questions from the concordance form which provided most answers . Focus on one drug group and have more consultation moments Background : Few studies have reported the efficacy of collaborative care involving family physicians and community pharmacists for patients with dyslipidemia . Methods : We r and omly assigned clusters consisting of at least two physicians and at least four pharmacists to provide collaborative care or usual care . Under the collaborative care model , pharmacists counselled patients about their medications , requested laboratory tests , monitored the effectiveness and safety of medications and patients ’ adherence to therapy , and adjusted medication dosages . After 12 months of follow-up , we assessed changes in low-density lipoprotein ( LDL ) cholesterol ( the primary outcome ) , the proportion of patients reaching their target lipid levels and changes in other risk factors . Results : Fifteen clusters representing a total of 77 physicians and 108 pharmacists were initially recruited , and a total of 51 physicians and 49 pharmacists were included in the final analyses . The collaborative care teams followed a total of 108 patients , and the usual care teams followed a total of 117 patients . At baseline , mean LDL cholesterol level was higher in the collaborative care group ( 3.5 v. 3.2 mmol/L , p = 0.05 ) . During the study , patients in the collaborative care group were less likely to receive high-potency statins ( 11 % v. 40 % ) , had more visits with health care professionals and more laboratory tests , were more likely to have their lipid-lowering treatment changed and were more likely to report lifestyle changes . At 12 months , the crude incremental mean reduction in LDL cholesterol in the collaborative care group was −0.2 mmol/L ( 95 % confidence interval [ CI ] −0.3 to −0.1 ) , and the adjusted reduction was −0.05 ( 95 % CI −0.3 to 0.2 ) . The crude relative risk of achieving lipid targets for patients in the collaborative care group was 1.10 ( 95 % CI 0.95 to 1.26 ) , and the adjusted relative risk was 1.16 ( 95 % CI 1.01 to 1.34 ) . Interpretation : Collaborative care involving physicians and pharmacists had no significant clinical impact on lipid control in patients with dyslipidemia . International St and ard R and omized Controlled Trial register no. IS RCT N66345533 |
13,539 | 29,304,148 | There was no difference in peak oxygen intake at 3 months in a trial of an SMS-based PA intervention .
Smoking cessation support delivered by SMS increases quitting rates .
Trials of PA interventions reporting outcomes ≥3 months showed no benefits .
There were at best modest benefits of diet and PA interventions . | BACKGROUND We conducted a systematic review to assess the effectiveness of smoking cessation , physical activity ( PA ) , diet , and alcohol reduction interventions delivered by mobile technology to prevent non-communicable diseases ( NCDs ) . | Objective : To assess the efficacy of an innovative smoking cessation intervention targeted to a multiethnic , economically disadvantaged HIV-positive population . Design : A two-group r and omized clinical trial compared a smoking cessation intervention delivered by cellular telephone with usual care approach . Methods : Current smokers from a large , inner city HIV/AIDS care center were recruited and r and omized to receive either usual care or a cellular telephone intervention . The usual care group received brief physician advice to quit smoking , targeted self-help written material s and nicotine replacement therapy . The cellular telephone intervention received eight counseling sessions delivered via cellular telephone in addition to the usual care components . Smoking-related outcomes were assessed at a 3-month follow-up . Results : The trial had 95 participants and 77 ( 81.0 % ) completed the 3-month follow-up assessment . Analyses indicated biochemically verified point prevalence smoking abstinence rates of 10.3 % for the usual care group and 36.8 % for the cellular telephone group ; participants who received the cellular telephone intervention were 3.6 times ( 95 % confidence interval , 1.3 - 9.9 ) more likely to quit smoking compared with participants who received usual care ( P = 0.0059 ) . Conclusions : These results suggest that individuals living with HIV/AIDS are receptive to , and can be helped by , smoking cessation treatment . In addition , smoking cessation treatment tailored to the special needs of individuals living with HIV/AIDS , such as counseling delivered by cellular telephone , can significantly increase smoking abstinence rates over that achieved by usual care Background Advances in technology allowed the development of a novel smoking cessation program delivered by video messages sent to mobile phones . This social cognitive theory-based intervention ( called “ STUB IT ” ) used observational learning via short video diary messages from role models going through the quitting process to teach behavioral change techniques . Objective The objective of our study was to assess the effectiveness of a multimedia mobile phone intervention for smoking cessation . Methods A r and omized controlled trial was conducted with 6-month follow-up . Participants had to be 16 years of age or over , be current daily smokers , be ready to quit , and have a video message-capable phone . Recruitment targeted younger adults predominantly through radio and online advertising . Registration and data collection were completed online , prompted by text messages . The intervention group received an automated package of video and text messages over 6 months that was tailored to self-selected quit date , role model , and timing of messages . Extra messages were available on dem and to beat cravings and address lapses . The control group also set a quit date and received a general health video message sent to their phone every 2 weeks . Results The target sample size was not achieved due to difficulty recruiting young adult quitters . Of the 226 r and omized participants , 47 % ( 107/226 ) were female and 24 % ( 54/226 ) were Maori ( indigenous population of New Zeal and ) . Their mean age was 27 years ( SD 8.7 ) , and there was a high level of nicotine addiction . Continuous abstinence at 6 months was 26.4 % ( 29/110 ) in the intervention group and 27.6 % ( 32/116 ) in the control group ( P = .8 ) . Feedback from participants indicated that the support provided by the video role models was important and appreciated . Conclusions This study was not able to demonstrate a statistically significant effect of the complex video messaging mobile phone intervention compared with simple general health video messages via mobile phone . However , there was sufficient positive feedback about the ease of use of this novel intervention , and the support obtained by observing the role model video messages , to warrant further investigation . Trial registration Australian New Zeal and Clinical Trials Registry Number : ACTRN12606000476538 ; http://www.anzctr.org.au/trial_view.aspx?ID=81688 ( Archived by WebCite at http://www.webcitation.org/5umMU4sZi Summary We evaluated the effectiveness of a mobile phone text-messaging based smoking cessation intervention package among Chinese adolescent smokers . Students aged 16–19 years were recruited from six vocational high schools located in Shanghai . We assigned the six schools to an intervention group or a control group by cluster r and omization . The 92 participants in the intervention group were given tailored information via mobile phone text-messaging for 12 weeks . The 87 participants in the control group were provided with a self-help pamphlet about smoking cessation instead . After the intervention , attitudes towards the disadvantages of smoking were significantly improved , and the level of nicotine dependence and cigarette dependence significantly decreased in the intervention group . The intervention group had a relatively higher self-reported 7-day abstinence compared to the control group and 30-day abstinence , but the differences were not significant . However , the intervention group had a significantly higher rate of smoking reduction ( 66 % vs. 35 % ) and moving forward in quitting stages ( 52 % vs. 18 % ) compared to the control group . The interactive and tailored assistance provided by the mobile phone text-messaging was effective in smoking behaviour intervention in Chinese adolescent smokers Background We hypothesized that a fully automated mobile health ( mHealth ) intervention with tracking and texting components would increase physical activity . Methods and Results mActive enrolled smartphone users aged 18 to 69 years at an ambulatory cardiology center in Baltimore , Maryl and . We used sequential r and omization to evaluate the intervention 's 2 core components . After establishing baseline activity during a blinded run‐in ( week 1 ) , in phase I ( weeks 2 to 3 ) , we r and omized 2:1 to unblinded versus blinded tracking . Unblinding allowed continuous access to activity data through a smartphone interface . In phase II ( weeks 4 to 5 ) , we r and omized unblinded participants 1:1 to smart texts versus no texts . Smart texts provided smartphone‐delivered coaching 3 times/day aim ed at individual encouragement and fostering feedback loops by a fully automated , physician‐written , theory‐based algorithm using real‐time activity data and 16 personal factors with a 10 000 steps/day goal . Forty‐eight out patients ( 46 % women , 21 % nonwhite ) enrolled with a mean±SD age of 58±8 years , body mass index of 31±6 kg/m2 , and baseline activity of 9670±4350 steps/day . Daily activity data capture was 97.4 % . The phase I change in activity was nonsignificantly higher in unblinded participants versus blinded controls by 1024 daily steps ( 95 % confidence interval [ CI ] , −580 to 2628 ; P=0.21 ) . In phase II , participants receiving texts increased their daily steps over those not receiving texts by 2534 ( 95 % CI , 1318 to 3750 ; P<0.001 ) and over blinded controls by 3376 ( 95 % CI , 1951 to 4801 ; P<0.001 ) . Conclusions An automated tracking‐texting intervention increased physical activity with , but not without , the texting component . These results support new mHealth tracking technologies as facilitators in need of behavior change drivers . Clinical Trial Registration URL : http:// Clinical Trials.gov/. Unique identifier : NCT01917812 Background Worksite nutrition and physical activity interventions are important to help overweight and obese employees lose weight , but costs and insufficient sustained motivation prevent the majority of these programs from succeeding . Tailored text messaging in aiding weight management has been effective in several studies , but no studies have evaluated the effect of a tailored text message service on weight loss in a worksite health promotion program . Objective We studied the efficacy of a tailored text-messaging intervention for obese male participants in a worksite weight loss program of 6 months duration . Methods The study was an unblinded , r and omized controlled trial . Men with a body mass index greater than 25 kg/m2 were recruited from the Korea District Heating Corporation , the Korea Expressway Corporation , and the Korea Gas Corporation . The participants were identified by nurse managers . Participants were r and omly allocated to 1 of the following 2 groups for 24 weeks : ( 1 ) intervention group , which received tailored text message reminders every other day plus 4 offline education sessions and brief counseling with monthly weight check by nurses for weight control over 6 months and ( 2 ) control group , which received the 4 offline education sessions and brief counseling with monthly weight check by nurses about weight control over 6 months . The primary outcome was the difference in weight loss at 6 months . A mixed-model repeated- measures analysis was performed to evaluate the effect of the intervention group ’s weight loss compared with the control group . Results A total of 205 obese men were r and omized into either the intervention ( n=104 ) or the control group ( n=101 ) . At the end of 6 months , the intervention group ( n=63 ) had lost 1.71 kg ( 95 % CI –2.53 to –0.88 ) and the control group ( n=59 ) had lost 1.56 kg ( 95 % CI –2.45 to –0.66 ) ; the difference between the 2 groups was not significant ( mean difference –0.15 , 95 % CI –1.36 to 1.07 ) . At the end of the study , 60 % ( 34/57 ) of the intervention group rated the message program as helpful for weight control and 46 % ( 26/57 ) would recommend the text message service to their friends . Conclusions Tailored text message reminders did not have a significant effect on weight loss in obese men as part of a worksite weight loss program . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 39629189 ; http://www.is rct n.com/IS RCT N39629189?q=39629189&filters=&sort=&offset=1&total Results = 1&page=1&pageSize=10 & search Type = basic- search ( Archived by WebCite at http://www.webcitation.org/6VsFkwJH6 ) Aim To determine the effectiveness and cost-effectiveness of a mobile phone intervention to improve exercise capacity and physical activity behaviour in people with ischaemic heart disease ( IHD ) . Methods and results In this single-blind , parallel , two-arm , r and omized controlled trial adults ( n = 171 ) with IHD were r and omized to receive a mobile phone delivered intervention ( HEART ; n = 85 ) plus usual care , or usual care alone ( n = 86 ) . Adult participants aged 18 years or more , with a diagnosis of IHD , were clinical ly stable as out patients , able to perform exercise , able to underst and and write English , and had access to the Internet . The HEART ( Heart Exercise And Remote Technologies ) intervention involved a personalized , automated package of text messages and a secure website with video messages aim ed at increasing exercise behaviour , delivered over 24 weeks . All participants were able to access usual community-based cardiac rehabilitation , which involves encouragement of physical activity and an offer to join a local cardiac support club . All outcomes were assessed at baseline and 24 weeks and included peak oxygen uptake ( PVO2 ; primary outcome ) , self-reported physical activity , health-related quality of life , self-efficacy and motivation ( secondary outcomes ) . Results showed no differences in PVO2 between the two groups ( difference −0.21 ml kg−1 min−1 , 95 % CI : −1.1 , 0.7 ; p = 0.65 ) at 24 weeks . However significant treatment effects were observed for selected secondary outcomes , including leisure time physical activity ( difference 110.2 min/week , 95 % CI : −0.8 , 221.3 ; p = 0.05 ) and walking ( difference 151.4 min/week , 95 % CI : 27.6 , 275.2 ; p = 0.02 ) . There were also significant improvements in self-efficacy to be active ( difference 6.2 % , 95 % CI : 0.2 , 12.2 ; p = 0.04 ) and the general health domain of the SF36 ( difference 2.1 , 95 % CI : 0.1 , 4.1 ; p = 0.03 ) at 24 weeks . The HEART programme was considered likely to be cost-effective for leisure time activity and walking . Conclusions A mobile phone intervention was not effective at increasing exercise capacity over and above usual care . The intervention was effective and probably cost-effective for increasing physical activity and may have the potential to augment existing cardiac rehabilitation services Background Despite promising data in Western countries , there is a dearth of research into the efficacy of text messaging-based smoking cessation programs in other setting s , including the Middle East , where smoking prevalence rates are higher . Objective This paper reports cessation rates observed in SMS Turkey , a text messaging-based smoking cessation program for adult smokers in Ankara , Turkey . Methods This study was a small-scale , parallel-group r and omized controlled trial ( RCT ) conducted in Ankara , Turkey . Participants were adult daily smokers who were seriously thinking about quitting in the next 15 days and living in Ankara , Turkey . The text messaging intervention , SMS Turkey , provided 6 weeks of daily messages aim ed at giving participants skills to help them quit smoking . Messages were sent in an automated fashion , except 2 days and 7 days after the initial quit day . On days 2 and 7 , the research assistant manually assigned participants to content “ paths ” based on whether they were still not smoking or had relapsed . The control arm received a brochure that provided similar information about smoking cessation . The main outcome measure was self-reported 3-month sustained abstinence , verified by carbon monoxide ( CO ) readings . Neither participants nor research ers were blinded to arm assignment . Results The 151 participants were r and omly assigned to 1 of 2 groups : 76 to the SMS Turkey intervention group and 75 to the brochure control group . Using intention to treat , all 151 participants were included in analyses . Three-month cessation trends were not significantly higher in the intervention group : 11 % intervention vs 5 % control had quit ( χ2 1=1.4 , P=.24 ; R2=2.0 , 95 % CI 0.62 - 6.3 ) . When the sample was stratified by sex , female intervention participants ( 14 % , n=5 ) were significantly more likely to have quit at 3 months than female control participants ( 0 % , n=0 ; χ2 1=3.7 , P=.05 ) . Among light smokers ( ie , those smoking less than 20 cigarettes per day ) , intervention participants ( 17 % , n=5 ) also were significantly more likely to have quit compared to control participants ( 0 % , n=0 ; χ2 1=5.3 , P=.02 ) . We noted no difference in cessation rates for males or heavy smokers . Participants experienced significant technology problems during the study . Some participants received duplicate text messages at least once during the trial ; others failed to receive some program messages . Neither receiving duplicate messages ( χ2 1=0.12 , P=.73 ) , or missing 5 or more program messages ( χ2 1=0.75 , P=.39 ) negatively affected quitting rates . Conclusions Although the study was not powered to detect statistically significant differences , as the primary aim was to provide estimates of effect size that could be used to better inform a power analysis for a larger trial , findings provide optimism that SMS Turkey may be able to affect quitting rates in environments with high smoking prevalence , such as Ankara , Turkey . The SMS Turkey software program did not work as well as it did 2 years previous . The system will need to be up date d to maintain software compatibility with ongoing technology evolution . Trial Registration Clinical trials.gov NCT00912795 http:// clinical trials.gov/ct2/show/NCT00912795 ( Archived by WebCite at http://www.webcitation.org/6Ch1cIA8l ) Objective To determine the feasibility and efficacy of a six-month , cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease ( COPD ) following pulmonary rehabilitation . Methods Participants who completed a two-week run-in were r and omly assigned to either MOBILE-Coached ( n = 9 ) or MOBILE-Self-Monitored ( n = 8) . All participants met with a nurse to develop an individualized exercise plan , were issued a pedometer and exercise booklet , and instructed to continue to log their daily exercise and symptoms . MOBILE-Coached also received weekly reinforcement text messages on their cell phones ; reports of worsening symptoms were automatically flagged for follow-up . Usability and satisfaction were assessed . Participants completed incremental cycle and six minute walk ( 6MW ) tests , wore an activity monitor for 14 days , and reported their health-related quality of life ( HRQL ) at baseline , three , and six months . Results The sample had a mean age of 68 ±11 and forced expiratory volume in one second 18 % predicted . Participants reported that logging their exercise and symptoms ( FEV1 ) of 40 ± was easy and that keeping track of their exercise helped them remain active . There were no differences between groups over time in maximal workload , 6MW distance , or HRQL ( p > 0.05 ) ; however , MOBILE-Self-Monitored increased total steps/day whereas MOBILE-Coached logged fewer steps over six months ( p = 0.04 ) . Conclusions We showed that it is feasible to deliver a cell phone-based exercise persistence intervention to patients with COPD post-rehabilitation and that the addition of coaching appeared to be no better than self-monitoring . The latter finding needs to be interpreted with caution since this was a purely exploratory study . Trial registration Clinical Trials.gov ( NCT00373932 ) The aim was to compare the effectiveness of untailored text messages for smoking cessation to tailored text messages delivered at a higher frequency . From February 2007 to August 2009 , 2030 users of an internet-based smoking cessation program with optional text message support aged 15 - 25 years were consecutively r and omized to versions of the program that offered either tailored or untailored text messages . Thirty-day point abstinence from smoking was measured self-reportedly at 12-months follow-up . Response rates were 36.3 % and 38.1 % in the tailored and untailored group , respectively . We analyzed the entire study population , as well as those opting for text messages ( n = 1619 ) . In intention-to-treat analysis with multiple imputation of missing data , the odds ratio for 30-day point abstinence was 1.28 ( 95 % CI 0.91 - 2.08 ) for the tailored compared with untailored messages . When restricting the analysis to those who had chosen to receive text messages , the corresponding odds ratio was 1.45 ( 95 % CI 1.01 - 2.08 ) . The higher long-term quit rates in the group receiving the tailored text messages compared with untailored text messages in the restricted analysis indicated that tailoring and higher frequency of text messages increases quit rates among young smokers It is well-known that the United States is facing an obesity epidemic , and the long-term sequelae are costly ( 1 , 2 ) . Research ers continue to search for effective weight-loss interventions that can be applied in outpatient setting s , but these are often time-consuming and re source -intensive , requiring repeated counseling ( 3 ) . It is no surprise that primary care providers often omit discussing weight loss with obese patients and rarely spend adequate time on counseling ( 4 , 5 ) . Smartphone applications ( apps ) may provide an alternative to re source -intensive weight-loss programs . In December 2013 , a survey by the Pew Research Center found that 58 % of Americans own smartphones and ownership is increasing among every demographic group , including low-income population s ( 6 ) . The nascent field of mobile health is rapidly exp and ing ; experts estimate that as many as 40000 health-related apps were available in 2012 , comprising a $ 718 million industry ( 7 ) . Many of these apps aim to help persons change behaviors to improve health , including weight loss , yet few have been rigorously evaluated . An effective app for reducing body weight could produce tremendous cost savings by preventing long-term complications , such as diabetes and cardiovascular events . To our knowledge , however , no studies have examined the effectiveness of delivering or prescribing an app for weight loss to patients in a clinical setting . We evaluated one of the most popular publicly available apps for weight loss : MyFitnessPal ( MFP ) ( MyFitnessPal ) . MFP has received the highest possible rating , 5 out of 5 stars , from thous and s of review ers on the Apple and And roid ( Google ) app store Web sites . It has nearly 1 million likes on Facebook , and the company reports more than 50 million registered users . MFP incorporates elements of social cognitive theory , including self-monitoring , goal setting , and feedback . We sought to test the effect of providing this free , widely used smartphone app for weight loss to patients in their primary care clinic . Methods Design Overview mFit ( The Mobile Fitness Project ) was a r and omized , controlled trial in which participants were r and omly assigned to receive usual primary care ( n= 107 ) or usual primary care plus the MFP app ( n= 105 ) ( Figure 1 ) . Assessment s were completed at baseline , 3 months , and 6 months between August 2012 and May 2013 . The institutional review board of the University of California , Los Angeles ( UCLA ) , approved the study , and all participants provided written informed consent . Figure 1 . Study flow diagram . * Among the 6 intervention group participants who withdrew , 3 reported not having enough time to use the app , 2 did not have time to return for follow-up , and 1 was no longer interested in participating in the study . Among the 8 control group participants who withdrew , 6 reported not having time to return for follow-up and 2 were no longer interested in participating in the study . Study data were collected on Apple iPads using Research Electronic Data Capture ( REDCap ) tools hosted at UCLA . REDCap is a secure , Web-based application design ed to support data capture for research studies , providing an intuitive interface , audit trails , and automated export ( 8) . Setting and Participants Participants were recruited from 2 UCLA primary care clinics that serve ethnically and socioeconomically diverse patient population s. Eligibility criteria included age 18 years or older , body mass index ( BMI ) of 25 kg/m2 or greater , and smartphone ownership . Participants also had to answer yes when asked , Are you interested in losing weight ? Exclusion criteria were current , planned , or previous pregnancy within 6 months ; receipt of hemodialysis ; life expectancy less than 6 months ; lack of interest in weight loss ; or current use of a smartphone app for weight loss . Screening and R and omization Patients were recruited during routine primary care visits at their respective clinics . The research team provided a script to medical assistants to use with any patients with BMI greater than 25 kg/m2 . Patients interested in enrollment were referred to the on-site research assistant , who screened , received consent from , and completed surveys with each patient . Participants were r and omly assigned in blocks by BMI of 25 to 30 kg/m2 and BMI greater than 30 kg/m2 to ensure roughly equal distribution of overweight and obese patients between the intervention and control groups . Our statistician used R ( R Foundation for Statistical Computing ) to generate the permuted block sequence . We printed the sequence and placed it in opaque envelopes . Research assistants helped intervention group participants download the MFP app onto their smartphone and showed them an instructional video developed by MFP . These participants also received a telephone call from the same research assistant 1 week after enrollment to assist with any technical problems with the app . Research assistants told control group patients to choose any activities you 'd like to lose weight , without specifying any particular interventions . Control group participants were aware that they were participating in a study of a weight-loss app but were blinded to the name of the app . To minimize contamination of the control group , providers and clinic staff were also blinded to the name of the app and to group assignment . At the 3-month follow-up visit , all participants received a 1-page educational h and out on healthy eating from www.myplate.gov . Participants received a $ 20 gift card for attending each follow-up visit . Each participant 's primary care provider was notified of their enrollment in the study . Blood pressure was measured at baseline , 3 months , and 6 months by trained research assistants using an automated monitor ( Dinamap , GE Medical Systems ) . Intervention We selected MFP as our intervention on the basis of 2 focus groups held with overweight primary care patients . Patients were asked about their impressions of various text messagebased programs and smartphone apps . Overall , there was much more interest in smartphone apps than text-based programs . A few participants stated they enjoyed using MFP , and a majority expressed great interest in trying it . Although we selected MFP as our intervention , there are many similar , publicly available apps that may be as popular as MFP . Some of these apps have been assessed in prior studies , but to our knowledge , none have been evaluated in a r and omized trial ( 9 ) . MFP was design ed by software engineers in collaboration with dietitians to create an app for calorie counting . The app provides a data base of more than 3 million foods and an easy-to-use interface for logging food and exercise . Users enter their current weight , goal weight , and goal rate of weight loss ( limited to 0.23 to 0.90 kg/wk ) . The MFP app then shows the user their daily , individualized calorie goal . Each day , the app displays the user 's calorie goal relative to their recorded caloric intake . MFP also generates real-time reports showing users their weight trend , caloric intake in the past week , and nutritional summaries of their diet ( for example , grams of fat , carbohydrates , and protein and milligrams of sodium ) . The app also includes a bar code scanner for store-bought foods and a social networking feature that enables users to find friends and share their progress . Study participants were encouraged to use the social networking feature with friends and to set reminders to log their food . MFP incorporates an evidence -based and theory-based approach to weight loss . Setting a realistic weight-loss goal of 0.23 to 0.90 kg/wk is supported in self-regulation theory and is a st and ard setting of the MFP app ( 10 ) . The social networking feature of MFP may be important , given prior studies demonstrating the benefits of social support on weight loss ( 11 ) . Self-monitoring , consisting of recording dietary intake , physical activity , and weight , is also strongly associated with weight loss ( 12 ) . One pilot trial recently found that adherence to diet self-monitoring is higher among patients using a smartphone app than among those using a paper diary ( 13 ) . Outcomes and Follow-up The primary outcome was change in weight at 6 months in the intervention group compared with the usual primary care group . Weight was measured at baseline , 3 months , and 6 months . Secondary outcomes were systolic blood pressure and 3 self-reported behavioral mediators of weight loss : exercise , dieting , and self-efficacy in weight loss . Data on these outcomes were also collected at baseline , 3 months , and 6 months ( Appendix A in the Data Supplement ) . The behavioral survey items were adapted from the TRIAD ( Translating Research Into Action for Diabetes ) study ( 14 ) and the Diabetes Empowerment Scale ( 15 ) . Data Supplement . Appendices The MFP company also shared user data with the research team to investigate frequency of app logins over time . Each time a participant opened the app counted as a login . We assessed for contamination at the end of the trial by asking control group participants whether they had used MFP in the past 6 months . At 6 months , participants in the intervention group completed a survey on their experience using MFP ( Appendix B in the Data Supplement ) . In addition , we interviewed 6 participants who lost more than 4.5 kg to ask whether they thought MFP helped them lose weight and , if so , how . Statistical Analysis We determined that a total sample size of 82 patients ( 41 per group ) would allow us 80 % power to detect a 2.5-kg difference in weight change at 6 months between the groups , assuming an SD of 4.0 kg . We set a goal of enrolling 180 participants to account for rates of attrition as high as 55 % . We used a linear mixed-effects model ( PROC MIXED ) to compare changes in weight , systolic blood pressure , and behavioral survey items between groups from baseline to 3 and 6 months while controlling for clinic site . Month , including baseline , was modeled as a categorical term in the mixed-effects model . This model Objective To test adding an interactive voice response (IVR)-supported protocol to st and ard quitline treatment to prevent relapse among recently quit smokers . Design Parallel r and omised controlled trial with three arms : st and ard quitline , st and ard plus technology enhanced quitline with 10 risk assessment s ( TEQ-10 ) , st and ard plus 20 TEQ assessment s ( TEQ-20 ) . Setting Quit For Life ( QFL ) programme . Participants 1785 QFL enrolees through 19 employers or health plans who were 24 + h quit . Interventions QFL is a 5-call telephone-based cessation programme including medications and web-based support . TEQ interventions included 10 or 20 IVR-delivered relapse risk assessment s over 8 weeks with automated transfer to counselling for those at risk . Main outcome measures Self-reported 7-day and 30-day abstinence assessed at 6-month and 12-month post-enrolment ( response rates : 61 % and 59 % , respectively ) . Missing data were imputed . Results 1785 were r and omised ( st and ard n=592 , TEQ-10 n=602 , TEQ-20 n=591 ) . Multiple imputation-derived , intent-to-treat 30-day quit rates ( 95 % CI ) at 6 months were 59.4 % ( 53.7 % to 63.8 % ) for st and ard , 62.3 % ( 57.7 % to 66.9 % ) for TEQ-10 , 59.4 % ( 53.7 % to 65.1 % ) for TEQ-20 and 30-day quit rates at 12 months were 61.2 % ( 55.6 % to 66.8 % ) for st and ard , 60.6 % ( 56.0 % to 65.2 % ) for TEQ-10 , 54.9 % ( 49.0 % to 60.9 % ) for TEQ-20 . There were no significant differences in quit rates . 73.3 % of TEQ participants were identified as at-risk by IVR assessment s ; on average , participants completed 0.41 IVR-transferred counselling calls . Positive risk assessment s identified participants less likely ( OR=0.56 , 95 % CI 0.42 to 0.76 ) to be abstinent at 6 months . Conclusions St and ard treatment was highly effective , with 61 % remaining abstinent at 12 months using multiple imputation intent-to-treat ( intent-to-treat missing = smoking quit rate : 38 % ) . TEQ assessment s identified quitters at risk for relapse . However , adding IVR-transferred counselling did not yield higher quit rates . Research is needed to determine if alternative design s can improve outcomes . Trial registration number NCT00888992 BACKGROUND Using regulatory focus theory , an intervention of daily weight loss-sustaining messages was developed and tested for acceptability , feasibility , and efficacy on helping people sustain weight loss . METHODS Participants ( n = 120 ) were r and omized to a promotion , prevention , or an attention-control text message group after completion of a weight loss program . Participants completed baseline assessment s , and reported their weight at 1 and 3 months postbaseline . RESULTS Participants found the message content and intervention acceptable and valuable . A minimum of one message per day delivered at approximately 8:00 am was deemed the optimal delivery time and frequency . The sustained weight loss rate at month 3 for the control , promotion , and prevention groups was 90 % , 95 % , and 100 % , respectively . Medium-to-large effects were observed for the promotion and prevention groups at month 1 and for prevention at month 3 relative to controls . The mean weight loss for promotion and prevention was 15 pounds , compared with 10 in the controls at month 3 . CONCLUSION A clinical ly significant decrease in mean weight , higher rate of sustained weight loss , and medium-to-large effects on sustained weight loss occurred in the promotion and prevention interventions . Tools such as this text message-based intervention that are constructed and guided by evidence -based content and theoretical constructs show promise in helping people sustain healthy behaviors that can lead to improved health outcomes IMPORTANCE Patients leaving residential treatment for alcohol use disorders are not typically offered evidence -based continuing care , although research suggests that continuing care is associated with better outcomes . A smartphone-based application could provide effective continuing care . OBJECTIVE To determine whether patients leaving residential treatment for alcohol use disorders with a smartphone application to support recovery have fewer risky drinking days than control patients . DESIGN , SETTING , AND PARTICIPANTS An unmasked r and omized clinical trial involving 3 residential programs operated by 1 nonprofit treatment organization in the Midwestern United States and 2 residential programs operated by 1 nonprofit organization in the Northeastern United States . In total , 349 patients who met the criteria for DSM-IV alcohol dependence when they entered residential treatment were r and omized to treatment as usual ( n = 179 ) or treatment as usual plus a smartphone ( n = 170 ) with the Addiction-Comprehensive Health Enhancement Support System ( A-CHESS ) , an application design ed to improve continuing care for alcohol use disorders . INTERVENTIONS Treatment as usual varied across programs ; none offered patients coordinated continuing care after discharge . A-CHESS provides monitoring , information , communication , and support services to patients , including ways for patients and counselors to stay in contact . The intervention and follow-up period lasted 8 and 4 months , respectively . MAIN OUTCOMES AND MEASURES Risky drinking days -- the number of days during which a patient 's drinking in a 2-hour period exceeded 4 st and ard drinks for men and 3 st and ard drinks for women , with st and ard drink defined as one that contains roughly 14 g of pure alcohol ( 12 oz of regular beer , 5 oz of wine , or 1.5 oz of distilled spirits ) . Patients were asked to report their risky drinking days in the previous 30 days on surveys taken 4 , 8 , and 12 months after discharge from residential treatment . RESULTS For the 8 months of the intervention and 4 months of follow-up , patients in the A-CHESS group reported significantly fewer risky drinking days than did patients in the control group , with a mean of 1.39 vs 2.75 days ( mean difference , 1.37 ; 95 % CI , 0.46 - 2.27 ; P = .003 ) . CONCLUSIONS AND RELEVANCE The findings suggest that a multifeatured smartphone application may have significant benefit to patients in continuing care for alcohol use disorders . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01003119 Background To our knowledge , no studies have evaluated whether weight loss can be promoted in overweight adults through the use of an intervention that is largely based on daily SMS ( Short Message Service : text ) and MMS ( Multimedia Message Service : small picture ) messages transmitted via mobile phones . Objective This paper describes the development and evaluation of a text message – based intervention design ed to help individuals lose or maintain weight over 4 months . Methods The study was a r and omized controlled trial , with participants being exposed to one of the following two conditions , lasting 16 weeks : ( 1 ) receipt of monthly printed material s about weight control ; ( 2 ) an intervention that included personalized SMS and MMS messages sent two to five times daily , printed material s , and brief monthly phone calls from a health counselor . The primary outcome was weight at the end of the intervention . A mixed-model repeated- measures analysis compared the effect of the intervention group to the comparison group on weight status over the 4-month intervention period . Analysis of covariance ( ANCOVA ) models examined weight change between baseline and 4 months after adjusting for baseline weight , sex , and age . Results A total of 75 overweight men and women were r and omized into one of the two groups , and 65 signed the consent form , completed the baseline question naire , and were included in the analysis . At the end of 4 months , the intervention group ( n = 33 ) lost more weight than the comparison group ( −1.97 kg difference , 95 % CI −0.34 to −3.60 kg , P = .02 ) after adjusting for sex and age . Intervention participants ’ adjusted average weight loss was 2.88 kg ( 3.16 % ) . At the end of the study , 22 of 24 ( 92 % ) intervention participants stated that they would recommend the intervention for weight control to friends and family . Conclusions Text messages might prove to be a productive channel of communication to promote behaviors that support weight loss in overweight adults . Trial Registration Clinical trials.gov NCT00415870 ; http:// clinical trials.gov/ct2/show/NCT00415870 ( Archived by WebCite at http://www.webcitation.org/5dnolbkFt Objective Cardiac rehabilitation ( CR ) is pivotal in preventing recurring events of myocardial infa rct ion ( MI ) . This study aims to investigate the effect of a smartphone-based home service delivery ( Care Assessment Platform ) of CR ( CAP-CR ) on CR use and health outcomes compared with a traditional , centre-based programme ( TCR ) in post-MI patients . Methods In this unblinded r and omised controlled trial , post-MI patients were r and omised to TCR ( n=60 ; 55.7±10.4 years ) and CAP-CR ( n=60 ; 55.5±9.6 years ) for a 6-week CR and 6-month self-maintenance period . CAP-CR , delivered in participants ’ homes , included health and exercise monitoring , motivational and educational material delivery , and weekly mentoring consultations . CAP-CR uptake , adherence and completion rates were compared with TCR using intention-to-treat analyses . Changes in clinical outcomes ( modifiable lifestyle factors , biomedical risk factors and health-related quality of life ) across baseline , 6 weeks and 6 months were compared within , and between , groups using linear mixed model regression . Results CAP-CR had significantly higher uptake ( 80 % vs 62 % ) , adherence ( 94 % vs 68 % ) and completion ( 80 % vs 47 % ) rates than TCR ( p<0.05 ) . Both groups showed significant improvements in 6-minute walk test from baseline to 6 weeks ( TCR : 537±86–584±99 m ; CAP-CR : 510±77–570±80 m ) , which was maintained at 6 months . CAP-CR showed slight weight reduction ( 89±20–88±21 kg ) and also demonstrated significant improvements in emotional state ( K10 : median ( IQR ) 14.6 ( 13.4–16.0 ) to 12.6 ( 11.5–13.8 ) ) , and quality of life ( EQ5D-Index : median ( IQR ) 0.84 ( 0.8–0.9 ) to 0.92 ( 0.9–1.0 ) ) at 6 weeks . Conclusions This smartphone-based home care CR programme improved post-MI CR uptake , adherence and completion . The home-based CR programme was as effective in improving physiological and psychological health outcomes as traditional CR . CAP-CR is a viable option towards optimising use of CR services . Trial registration number ANZCTR12609000251224 The present trial examined the effectiveness of brief interventions for smokers who joined the Hong Kong Quit to Win Contest to quit smoking . A block r and omized controlled trial allocated 1003 adult daily smokers to three groups : ( i ) The TEL group ( n = 338 ) received a 5-min nurse-led telephone counselling ; ( ii ) The SMS group ( n = 335 ) received eight text messages through mobile phone and ( iii ) The CONTROL group ( n = 330 ) did not receive the above interventions . Participants with biochemically verified abstinence at 6-month follow-up could receive cash incentive . The primary outcome was the self-reported 7-day point prevalence ( PP ) of tobacco abstinence at 6-month follow-up . The abstinence rate in the TEL , SMS and CONTROL group was 22.2 , 20.6 and 20.3 % , respectively ( P for TEL versus CONTROL = 0.32 ; P for SMS versus CONTROL = 0.40 ) . When abstinence at 2- , 6- and 12-month follow-up was modelled simultaneously , the TEL group had a higher abstinence than the CONTROL group ( Adjusted OR = 1.38 , 95 % CI = 1.01 - 1.88 , P = 0 .04 ) . In the Quit to Win Contest , the brief telephone counselling might have increased abstinence , but the text messages had no significant effect . Further studies on intensive intervention and interactive messaging services are warranted Objectives : To determine the effectiveness of a mobile phone text messaging smoking cessation programme . Design : R and omised controlled trial Setting : New Zeal and Participants : 1705 smokers from throughout New Zeal and who wanted to quit , were aged over 15 years , and owned a mobile phone were r and omised to an intervention group that received regular , personalised text messages providing smoking cessation advice , support , and distraction , or to a control group . All participants received a free month of text messaging ; starting for the intervention group on their quit day to assist with quitting , and starting for the control group at six months to encourage follow up . Follow up data were available for 1624 ( 95 % ) at six weeks and 1265 ( 74 % ) at six months . Main outcome measures : The main trial outcome was current non-smoking ( that is , not smoking in the past week ) six weeks after r and omisation . Secondary outcomes included current non-smoking at 12 and 26 weeks . Results : More participants had quit at six weeks in the intervention compared to the control group : 239 ( 28 % ) v 109 ( 13 % ) , relative risk 2.20 ( 95 % confidence interval 1.79 to 2.70 ) , p < 0.0001 . This treatment effect was consistent across subgroups defined by age , sex , income level , or geographic location ( p homogeneity > 0.2 ) . The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests . Reported quit rates remained high at six months , but there was some uncertainty about between group differences because of incomplete follow up . Conclusions : This programme offers potential for a new way to help young smokers to quit , being affordable , personalised , age appropriate , and not location dependent . Future research should test these findings in different setting s , and provide further assessment of long term quit rates Background Daily self-monitoring of diet and physical activity behaviors is a strong predictor of weight loss success . Text messaging holds promise as a viable self-monitoring modality , particularly among racial/ethnic minority population s. Objective This pilot study evaluated the feasibility of a text messaging intervention for weight loss among predominantly black women . Methods Fifty obese women were r and omized to either a 6-month intervention using a fully automated system that included daily text messages for self-monitoring tailored behavioral goals ( eg , 10,000 steps per day , no sugary drinks ) along with brief feedback and tips ( n=26 ) or to an education control arm ( n=24 ) . Weight was objective ly measured at baseline and at 6 months . Adherence was defined as the proportion of text messages received in response to self-monitoring prompts . Results The average daily text messaging adherence rate was 49 % ( SD 27.9 ) with 85 % ( 22/26 ) texting self-monitored behavioral goals 2 or more days per week . Approximately 70 % ( 16/23 ) strongly agreed that daily texting was easy and helpful and 76 % ( 16/21 ) felt the frequency of texting was appropriate . At 6 months , the intervention arm lost a mean of 1.27 kg ( SD 6.51 ) , and the control arm gained a mean of 1.14 kg ( SD 2.53 ; mean difference –2.41 kg , 95 % CI –5.22 to 0.39 ; P=.09 ) . There was a trend toward greater text messaging adherence being associated with greater percent weight loss ( r=–.36 ; P=.08 ) , but this did not reach statistical significance . There was no significant association between goal attainment and text messaging adherence and no significant predictors of adherence . Conclusions Given the increasing penetration of mobile devices , text messaging may be a useful self-monitoring tool for weight control , particularly among population s most in need of intervention . Trial Registration Clinical trials.gov : NCT00939081 ; http:// clinical trials.gov/show/NCT00939081 ( Archived by WebCite at http://www.webcitation.org/6KiIIcnk1 ) Background Physical inactivity is a major public health problem . The It ’s LiFe ! monitoring and feedback tool embedded in the Self-Management Support Program ( SSP ) is an attempt to stimulate physical activity in people with chronic obstructive pulmonary disease or type 2 diabetes treated in primary care . Objective Our aim was to evaluate whether the SSP combined with the use of the monitoring and feedback tool leads to more physical activity compared to usual care and to evaluate the additional effect of using this tool on top of the SSP . Methods This was a three-armed cluster r and omised controlled trial . Twenty four family practice s were r and omly assigned to one of three groups in which participants received the tool + SSP ( group 1 ) , the SSP ( group 2 ) , or care as usual ( group 3 ) . The primary outcome measure was minutes of physical activity per day . The secondary outcomes were general and exercise self-efficacy and quality of life . Outcomes were measured at baseline after the intervention ( 4 - 6 months ) , and 3 months thereafter . Results The group that received the entire intervention ( tool + SSP ) showed more physical activity directly after the intervention than Group 3 ( mean difference 11.73 , 95 % CI 6.21 - 17.25 ; P<.001 ) , and Group 2 ( mean difference 7.86 , 95 % CI 2.18 - 13.54 ; P=.003 ) . Three months after the intervention , this effect was still present and significant ( compared to Group 3 : mean difference 10.59 , 95 % CI 4.94 - 16.25 ; P<.001 ; compared to Group 2 : mean difference 9.41 , 95 % CI 3.70 - 15.11 ; P<.001 ) . There was no significant difference in effect between Groups 2 and 3 on both time points . There was no interaction effect for disease type . Conclusions The combination of counseling with the tool proved an effective way to stimulate physical activity . Counseling without the tool was not effective . Future research about the cost-effectiveness and application under more tailored conditions and in other target groups is recommended . Trial Registration Clinical Trials.gov : NCT01867970 , https:// clinical trials.gov/ct2/show/NCT01867970 ( archived by WebCite at http://www.webcitation.org/6a2qR5BSr ) AIMS To test the feasibility , acceptability and initial effectiveness of a text message-based aftercare treatment programme among alcohol out patients . METHODS Clients treated for alcohol use disorders from three Swiss outpatient alcohol treatment centres were invited by their counsellors to participate in a study testing an interactive aftercare programme employing the use of text messages and personal phone calls . Fifty study participants were r and omly assigned to either the 6-month aftercare programme ( n = 25 ) or treatment as usual ( n = 25 ) . The intervention consisted of ( a ) monitoring of self-selected drinking goals at regular intervals , ( b ) motivational text messages to stick to self-selected drinking goals and ( c ) proactive telephone calls from counsellors when participants neglected to stick to their drinking goals or expressed a need for support . Follow-up interviews were conducted 6 months after r and omization . RESULTS Throughout the programme , participants received a total of 421 text message prompts . Out of these , participants provided valid replies to 371 ( 88.1 % ) within 48 h. Out of the 25 participants in the intervention group , 11 ( 44.0 % ) sent at least one call-for-help reply . Based on complete case data , at risk alcohol use at follow-up was 41.7 % in the control group and 28.6 % in the intervention group ( OR = 0.56 , 95 % CI = 0.16 - 1.95 , P = 0.36 ) . CONCLUSIONS The interactive low-intensive aftercare programme was well accepted by the participants . Testing its efficacy within an adequately powered r and omized controlled trial might be reasonable Summary Background Smoking cessation programmes delivered via mobile phone text messaging show increases in self-reported quitting in the short term . We assessed the effect of an automated smoking cessation programme delivered via mobile phone text messaging on continuous abstinence , which was biochemically verified at 6 months . Methods In this single-blind , r and omised trial , undertaken in the UK , smokers willing to make a quit attempt were r and omly allocated , using an independent telephone r and omisation system , to a mobile phone text messaging smoking cessation programme ( txt2stop ) , comprising motivational messages and behavioural-change support , or to a control group that received text messages unrelated to quitting . The system automatically generated intervention or control group texts according to the allocation . Outcome assessors were masked to treatment allocation . The primary outcome was self-reported continuous smoking abstinence , biochemically verified at 6 months . All analyses were by intention to treat . This study is registered , number IS RCT N 80978588 . Findings We assessed 11 914 participants for eligibility . 5800 participants were r and omised , of whom 2915 smokers were allocated to the txt2stop intervention and 2885 were allocated to the control group ; eight were excluded because they were r and omised more than once . Primary outcome data were available for 5524 ( 95 % ) participants . Biochemically verified continuous abstinence at 6 months was significantly increased in the txt2stop group ( 10·7 % txt2stop vs 4·9 % control , relative risk [ RR ] 2·20 , 95 % CI 1·80–2·68 ; p<0·0001 ) . Similar results were obtained when participants that were lost to follow-up were treated as smokers ( 268 [ 9 % ] of 2911 txt2stop vs 124 [ 4 % ] of 2881 control [ RR 2·14 , 95 % CI 1·74–2·63 ; p<0·0001 ] ) , and when they were excluded ( 268 [ 10 % ] of 2735 txt2stop vs 124 [ 4 % ] of 2789 control [ 2·20 , 1·79–2·71 ; p<0·0001 ] ) . No significant heterogeneity was shown in any of the prespecified subgroups . Interpretation The txt2stop smoking cessation programme significantly improved smoking cessation rates at 6 months and should be considered for inclusion in smoking cessation services . Funding UK Medical Research Council , Primary Care Research Networks OBJECTIVE To examine adherence to , satisfaction with , and preliminary efficacy of mobile phone short message service ( SMS ) to promote health behaviors in school-aged children . METHODS A total of 49 children ( aged 8 - 10 years ) were r and omized by school classes into a monitoring vs no-monitoring group . All children participated in 2 educational group sessions that focused on health behaviors : the advantages of increasing fruit and vegetable consumption and physical activity , and decreasing screen time . The monitoring group also reported daily behavior using SMS and received supportive feedback for 8 weeks . RESULTS Children su bmi tted 61 % of the required SMS , which indicated good adherence to the intervention . A number of children ( 95 % ) reported being satisfied with the program . Analyses of covariance indicated increase in fruit and vegetable consumption ( χ² [ 2 ] = 7.27 ; P < .05 ) and a decrease in screen time ( χ² [ 2 ] = 6.79 ; P < .05 ) . CONCLUSIONS AND IMPLICATION S The current SMS intervention was a useful tool to monitor and promote health behaviors in children Background . The established interventions for weight loss are re source intensive which can create barriers for full participation and ultimate translation . The major goal of this pilot study was to evaluate the feasibility , acceptability , and preliminary efficacy of theoretically based behavioral interventions delivered by smartphone technology . Methods . The study r and omized 68 obese adults to receive one of four interventions for six months : ( 1 ) intensive counseling intervention , ( 2 ) intensive counseling plus smartphone intervention , ( 3 ) a less intensive counseling plus smartphone intervention , and ( 4 ) smartphone intervention only . The outcome measures of weight , BMI , waist circumference , and self-reported dietary intake and physical activity were assessed at baseline and six months . Results . The sample was 78 % female and 49 % African American , with an average age of 45 years , and average BMI of 34.3 kg/m2 . There were trends for differences in weight loss among the four intervention groups . Participants in the intensive counseling plus self-monitoring smartphone group and less intensive counseling plus self-monitoring smartphone group tended to lose more weight than other groups ( 5.4 kg and 3.3 kg , resp . ) . Conclusions . The results of this pilot trial of a weight loss intervention provide preliminary support for using a smartphone application for self-monitoring as an adjunct to behavioral counseling BACKGROUND People living with human immunodeficiency virus (HIV)/AIDS ( PLWHA ) have a substantially higher prevalence of cigarette smoking compared to the general population . In addition , PLWHA are particularly susceptible to the adverse health effects of smoking . Our primary objective was to design and test the efficacy over 12 months of a smoking cessation intervention targeting PLWHA . METHODS Participants were enrolled from an urban HIV clinic with a multiethnic and economically disadvantaged patient population . Participants received smoking cessation treatment either through usual care ( UC ) or counseling delivered by a cell phone intervention ( CPI ) . The 7-day point prevalence abstinence was evaluated at 3 , 6 , and 12 months using logistic regression and generalized linear mixed models . RESULTS We r and omized 474 HIV-positive smokers to either the UC or CPI group . When evaluating the overall treatment effect ( 7-day abstinence outcomes from 3- , 6- , and 12-month follow-ups ) , participants in the CPI group were 2.41 times ( P = .049 ) more likely to demonstrate abstinence compared to the UC group . The treatment effect was strongest at the 3-month follow-up ( odds ratio = 4.3 , P < .001 ) , but diminished at 6 and 12 months ( P > .05 ) . CONCLUSIONS Cell phone-delivered smoking cessation treatment has a positive impact on abstinence rates compared to a usual care approach . Future research should focus on strategies for sustaining the treatment effect in the long term Background Given the global prevalence of insufficient physical activity ( PA ) , effective interventions that attenuate age-related decline in PA levels are needed . Mobile phone interventions that positively affect health ( mHealth ) show promise ; however , their impact on PA levels and fitness in young people is unclear and little is known about what makes a good mHealth app . Objective The aim was to determine the effects of two commercially available smartphone apps ( Zombies , Run and Get Running ) on cardiorespiratory fitness and PA levels in insufficiently active healthy young people . A second aim was to identify the features of the app design that may contribute to improved fitness and PA levels . Methods Apps for IMproving FITness ( AIM FIT ) was a 3-arm , parallel , r and omized controlled trial conducted in Auckl and , New Zeal and . Participants were recruited through advertisements in electronic mailing lists , local newspapers , flyers posted in community locations , and presentations at schools . Eligible young people aged 14 - 17 years were allocated at r and om to 1 of 3 conditions : ( 1 ) use of an immersive app ( Zombies , Run ) , ( 2 ) use of a nonimmersive app ( Get Running ) , or ( 3 ) usual behavior ( control ) . Both smartphone apps consisted of a fully automated 8-week training program design ed to improve fitness and ability to run 5 km ; however , the immersive app featured a game-themed design and narrative . Intention-to-treat analysis was performed using data collected face-to-face at baseline and 8 weeks , and all regression models were adjusted for baseline outcome value and gender . The primary outcome was cardiorespiratory fitness , objective ly assessed as time to complete the 1-mile run/walk test at 8 weeks . Secondary outcomes were PA levels ( accelerometry and self-reported ) , enjoyment , psychological need satisfaction , self-efficacy , and acceptability and usability of the apps . Results A total of 51 participants were r and omized to the immersive app intervention ( n=17 ) , nonimmersive app intervention ( n=16 ) , or the control group ( n=18 ) . The mean age of participants was 15.7 ( SD 1.2 ) years ; participants were mostly NZ Europeans ( 61 % , 31/51 ) and 57 % ( 29/51 ) were female . Overall retention rate was 96 % ( 49/51 ) . There was no significant intervention effect on the primary outcome using either of the apps . Compared to the control , time to complete the fitness test was –28.4 seconds shorter ( 95 % CI –66.5 to 9.82 , P=.20 ) for the immersive app group and –24.7 seconds ( 95 % CI –63.5 to 14.2 , P=.32 ) for the nonimmersive app group . No significant intervention effects were found for secondary outcomes . Conclusions Although apps have the ability to increase reach at a low cost , our pragmatic approach using readily available commercial apps as a st and -alone instrument did not have a significant effect on fitness . However , interest in future use of PA apps is promising and highlights a potentially important role of these tools in a multifaceted approach to increase fitness , promote PA , and consequently reduce the adverse health outcomes associated with insufficient activity . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN12613001030763 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?ACTRN=12613001030763 ( Archived by WebCite at http://www.webcitation.org/6aasfJVTJ ) Background Sleep and physical activity are two health behaviors associated with improved smoking cessation outcomes . Text message-based interventions have previously been used to promote physical activity and smoking cessation ; however , this type of intervention has not targeted sleep habits . This study examined the effectiveness of a text message-based active control intervention in improving sleep and physical activity habits among a U.S. national sample of young adult smokers participating in a smoking cessation intervention . Methods This study was a secondary analysis of data from the Stop My Smoking USA r and omized controlled trial . Baseline and 3-month follow-up data were collected from 116 young adult smokers ( mean age 21.8 years , SD = 2.1 ) who were r and omized at a 2:1 ratio to receive a 6-week text messaging program focused on either smoking cessation ( n = 72 ) , or improving sleep and physical activity ( n = 44 ) . Three main outcomes were assessed : 1 ) sleep quantity ( on work/school nights , and non-work/non-school nights ) , 2 ) sleep quality , and 3 ) physical activity at follow-up . Multivariable linear regression analysis was used to quantify the differences in these outcomes between the groups . To identify possible effect modification by baseline sleep and physical activity , the sample was stratified by indicators defined for both of these variables . Results At follow-up , sleep quantity and quality were similar for participants in the smoking cessation and sleep/activity groups when assessed among the total sample and those sleeping ≥6 hours/night at baseline . Among short sleepers ( < 6 hours/night at baseline ) , sleep quantity on work/school nights improved for those receiving sleep/activity messages compared to those receiving smoking cessation messages , after adjusting for covariates ( β̂$$ \widehat{\beta } $ $ = 1.373 , 95 % CI [ 0.262 , 2.484 ] ; p = 0.02 ) . Physical activity at follow-up was similar for the two groups , when examined among the total sample and when stratified by baseline activity level . Conclusions This study provides preliminary evidence that a text message-based intervention may be a promising approach for improving sleep quantity among young adult smokers who are short sleepers and interested in quitting smoking . Similar programs should be further explored as a novel approach for improving sleep habits among individuals with insufficient sleep . Trial registration Clinical Trials.gov Objectives To determine the effect on weight of two Mobile technology-based ( mHealth ) behavioral weight loss interventions in young adults . Methods R and omized , controlled comparative effectiveness trial in 18–35 year olds with BMI ≥ 25 kg/m2 ( overweight/obese ) , with participants r and omized to 24 months of mHealth intervention delivered by interactive smartphone application on a cell phone ( CP ) ; personal coaching enhanced by smartphone self-monitoring ( PC ) ; or Control . Results The 365 r and omized participants had mean baseline BMI of 35 kg/m2 . Final weight was measured in 86 % of participants . CP was not superior to Control at any measurement point . PC participants lost significantly more weight than Controls at 6 months ( net effect −1.92 kg [ CI −3.17 , −0.67 ] , p=0.003 ) , but not at 12 and 24 months . Conclusions Despite high intervention engagement and study retention , the inclusion of behavioral principles and tools in both interventions , and weight loss in all treatment groups , CP did not lead to weight loss and PC did not lead to sustained weight loss relative to control . Although mHealth solutions offer broad dissemination and scalability , the CITY results sound a caution ary note concerning intervention delivery by mobile applications . Effective intervention may require the efficiency of mobile technology , the social support and human interaction of personal coaching , and an adaptive approach to intervention design . Trial Registration Clinical Trials.gov Identifier NCT01092364 . https:// clinical OBJECTIVE To investigate the short- and long-term effectiveness and the predictors of weight loss in a mobile phone weight-loss programme among healthy overweight adults . DESIGN One hundred and twenty-five healthy , overweight ( BMI = 26 - 36 kg/m2 ) , 25 - 44-year-old , screened volunteers were r and omized to an experimental group ( n 62 ) to use a mobile phone-operated weight-loss programme or to a control group ( n 63 ) with no intervention . Via text messaging , the programme instructed a staggered reduction of food intake and daily weight reporting with immediate tailored feedback . Assessment s were at 0 , 3 , 6 , 9 and 12 months for the experimental group ; at 0 and 12 months for the control group . Main outcome variables were changes in body weight and waist circumference . RESULTS By 12 months the experimental group had lost significantly more weight than the control group ( 4.5 ( sd 5.0 ) v. 1.1 ( sd 5.8 ) kg ; F(1,80 ) = 8.0 , P = 0.006 ) and had a greater reduction in waist circumference ( 6.3 ( sd 5.3 ) v. 2.4 ( sd 5.4 ) cm ; F(1,80 ) = 55.2 , P = 0.0001 ) . Early weight loss , self-efficacy , contact frequency , attitudes towards the medium , changes in work and family life and changes made in dietary habits were the strongest predictors of weight loss . CONCLUSIONS This mobile phone weight-loss programme was effective in short- and long-term weight loss . As a minimum-advice , maximal-contact programme , it offers ideas for future weight-loss programmes OBJECTIVE To test the efficacy in promoting brisk walking of two theory-based interventions that incorporate implementation intentions and text message ( Short Message Service ; SMS ) reminders directed at one 's walking-related plans or goals . DESIGN Participants ( N = 149 ) were r and omized to one of three conditions ( implementation intention + SMS plan reminder , implementation intention + SMS goal reminder , control ) before completing measures at baseline and follow-up 4 weeks later . At follow-up , the experimental groups were given a surprise recall task concerning their plans . All participants completed an equivalent goal recall task . MAIN OUTCOME MEASURES Vali date d self-report measures of physical activity and measures of implementation intention and goal recall , weight , and waist-to-hip ratio . RESULTS Both intervention groups increased their brisk walking relative to the control group , without reducing other physical activity . The goal reminder group lost the most weight . The SMS plan reminder group recalled more of their plans than the SMS goal reminder group , but the latter were more successful in goal recall . CONCLUSION Both interventions can promote brisk walking in sedentary population s. Text messages aid the recall of , and could enhance interventions that target , implementation intentions and goals BACKGROUND Type 2 diabetes can often be prevented by lifestyle modification ; however , successful lifestyle intervention programmes are labour intensive . Mobile phone messaging is an inexpensive alternative way to deliver educational and motivational advice about lifestyle modification . We aim ed to assess whether mobile phone messaging that encouraged lifestyle change could reduce incident type 2 diabetes in Indian Asian men with impaired glucose tolerance . METHODS We did a prospect i ve , parallel-group , r and omised controlled trial between Aug 10 , 2009 , and Nov 30 , 2012 , at ten sites in southeast India . Working Indian men ( aged 35 - 55 years ) with impaired glucose tolerance were r and omly assigned ( 1:1 ) with a computer-generated r and omisation sequence to a mobile phone messaging intervention or st and ard care ( control group ) . Participants in the intervention group received frequent mobile phone messages compared with controls who received st and ard lifestyle modification advice at baseline only . Field staff and participants were , by necessity , not masked to study group assignment , but allocation was concealed from laboratory personnel as well as principal and co-investigators . The primary outcome was incidence of type 2 diabetes , analysed by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00819455 . RESULTS We assessed 8741 participants for eligibility . 537 patients were r and omly assigned to either the mobile phone messaging intervention ( n=271 ) or st and ard care ( n=266 ) . The cumulative incidence of type 2 diabetes was lower in those who received mobile phone messages than in controls : 50 ( 18 % ) participants in the intervention group developed type 2 diabetes compared with 73 ( 27 % ) in the control group ( hazard ratio 0·64 , 95 % CI 0·45 - 0·92 ; p=0·015 ) . The number needed to treat to prevent one case of type 2 diabetes was 11 ( 95 % CI 6 - 55 ) . One patient in the control group died suddenly at the end of the first year . We recorded no other serious adverse events . INTERPRETATION Mobile phone messaging is an effective and acceptable method to deliver advice and support towards lifestyle modification to prevent type 2 diabetes in men at high risk . FUNDING The UK India Education and Research Initiative , the World Diabetes Foundation IMPORTANCE Cardiovascular disease prevention , including lifestyle modification , is important but underutilized . Mobile health strategies could address this gap but lack evidence of therapeutic benefit . OBJECTIVE To examine the effect of a lifestyle-focused semipersonalized support program delivered by mobile phone text message on cardiovascular risk factors . DESIGN AND SETTING The Tobacco , Exercise and Diet Messages ( TEXT ME ) trial was a parallel-group , single-blind , r and omized clinical trial that recruited 710 patients ( mean age , 58 [ SD , 9.2 ] years ; 82 % men ; 53 % current smokers ) with proven coronary heart disease ( prior myocardial infa rct ion or proven angiographically ) between September 2011 and November 2013 from a large tertiary hospital in Sydney , Australia . INTERVENTIONS Patients in the intervention group ( n = 352 ) received 4 text messages per week for 6 months in addition to usual care . Text messages provided advice , motivational reminders , and support to change lifestyle behaviors . Patients in the control group ( n=358 ) received usual care . Messages for each participant were selected from a bank of messages according to baseline characteristics ( eg , smoking ) and delivered via an automated computerized message management system . The program was not interactive . MAIN OUTCOMES AND MEASURES The primary end point was low-density lipoprotein cholesterol ( LDL-C ) level at 6 months . Secondary end points included systolic blood pressure , body mass index ( BMI ) , physical activity , and smoking status . RESULTS At 6 months , levels of LDL-C were significantly lower in intervention participants , with concurrent reductions in systolic blood pressure and BMI , significant increases in physical activity , and a significant reduction in smoking . The majority reported the text messages to be useful ( 91 % ) , easy to underst and ( 97 % ) , and appropriate in frequency ( 86 % ) . [ table : see text ] . CONCLUSIONS AND RELEVANCE Among patients with coronary heart disease , the use of a lifestyle-focused text messaging service compared with usual care result ed in a modest improvement in LDL-C level and greater improvement in other cardiovascular disease risk factors . The duration of these effects and hence whether they result in improved clinical outcomes remain to be determined . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12611000161921 We developed and tested a mobile phone application ( app ) to support individuals embarking on a partial meal replacement programme ( MRP ) . Overweight or obese women were r and omly allocated to one of two study groups . The intervention group received an MRP Support app . The control group received a static app based on the information available with the MRP . A total of 58 adult women ( Support n = 28 ; Control n = 30 ) participated in the 8-week trial . Their BMI was 26 - 43 kg/m2 . Usage data suggested that the intervention group were more engaged with using the app throughout the study period . Mixed modelling revealed that the difference in weight loss between the intervention and control groups ( estimated mean , EM = 3.2 % and 2.2 % respectively ) was not significant ( P = 0.08 ) . Objective data suggested that users of the Support app were more engaged than those using the control app . A total of 1098 prompts ( 54 % ) asking people in the intervention group to enter their meals were completed prior to the evening prompt . Women in the intervention group reported a greater increase in positive affect ( i.e. mood ) than those in the control group ( EM = 0.48 and −0.01 , respectively ) ( P = 0.012 ) . At Week 8 , those in the control group reported a greater decrease in the effort they were willing to put into staying on the diet than those who received the Support app ( EM = −2.8 and −1.4 , respectively ) ( P = 0.024 ) . The Support app could be a useful adjunct to existing MRPs for psychological outcomes BACKGROUND Text messaging programs on mobile phones have shown some promise in helping people quit smoking . Text2Quit is an automated , personalized , interactive mobile health program that sends text messages to offer advice , support , and reminders about quitting smoking . PURPOSE To evaluate the effect of Text2Quit on biochemically confirmed repeated point prevalence abstinence in the context of an RCT conducted in the U.S. METHODS Participants ( n=503 ) were recruited on the Internet and r and omized to receive Text2Quit or self-help material . Between 2011 and 2013 , participants were surveyed at baseline and at 1 , 3 , and 6 months post-enrollment to assess smoking status . Saliva was collected from participants who reported not smoking in the past 7 days at the 6-month follow-up . An intent to treat analysis was used , and those lost to follow-up were categorized as smokers . All analyses were completed in 2013 . RESULTS Biochemically confirmed repeated point prevalence abstinence favored the intervention group , with 11.1 % abstinent compared to 5.0 % of the control group ( relative risk=2.22 , 95 % CI=1.16 , 4.26 , p<0.05 ) . Similarly , self-reported repeated point prevalence abstinence was higher in the intervention group ( 19.9 % ) than in the control group ( 10.0 % ) ( p<0.01 ) . Effects were found to be uniform across the analyzed demographic subgroups , although suggestive of a larger effect for non-whites than whites . CONCLUSIONS These results provide initial support for the relative efficacy of the Text2Quit program OBJECTIVE To assess whether pedometers and text messaging increase physical activity in adolescents with type 1 diabetes . RESEARCH DESIGN AND METHODS A 12-week r and omized controlled trial was conducted . A total of 78 subjects participated in the trial ( mean ± SD age 14.4 ± 2.37 years , 36 [ 47 % ] male ) . Intervention participants wore an open pedometer and received regular motivational text messages . Control participants received usual care . Primary outcomes were daily step count ( 4-day closed pedometer ) and physical activity question naire . RESULTS Baseline median step count was 11,063 steps/day ( range 1,541–20,158 ) . At 12 weeks , mean daily step count reduced by 840 ( 95 % CI −1,947 to 266 ) in the control group and by 22 ( −1,407 to 1,364 ) in the intervention group ( P = 0.4 ) . Mean self-reported moderate or vigorous physical activity increased by 38.5 min/week in the control group and by 48.4 in the intervention group ( P = 0.9 ) . CONCLUSIONS A 12-week intervention using pedometers and text messaging as motivational tools in adolescents with type 1 diabetes did not increase physical activity INTRODUCTION Direct-to-consumer mHealth devices are a potential asset to behavioral research but rarely tested as intervention tools . This trial examined the accelerometer-based Fitbit tracker and website as a low-touch physical activity intervention . The purpose of this study is to evaluate , within an RCT , the feasibility and preliminary efficacy of integrating the Fitbit tracker and website into a physical activity intervention for postmenopausal women . METHODS Fifty-one inactive , postmenopausal women with BMI ≥25.0 were r and omized to a 16-week web-based self-monitoring intervention ( n=25 ) or comparison group ( n=26 ) . The Web-Based Tracking Group received a Fitbit , instructional session , and follow-up call at 4 weeks . The comparison group received a st and ard pedometer . All were asked to perform 150 minutes/week of moderate to vigorous physical activity ( MVPA ) . Physical activity outcomes were measured by the ActiGraph GT3X+ accelerometer . RESULTS Data were collected and analyzed in 2013 - 2014 . Participants were aged 60 ( SD=7 ) years with BMI of 29.2 ( 3.5 ) kg/m(2 ) . Relative to baseline , the Web-Based Tracking Group increased MVPA by 62 ( 108 ) minutes/week ( p<0.01 ) ; 10-minute MVPA bouts by 38 ( 83 ) minutes/week ( p=0.008 ) ; and steps by 789 ( 1,979 ) ( p=0.01 ) , compared to non-significant increases in the Pedometer Group ( between-group p=0.11 , 0.28 , and 0.30 , respectively ) . The Web-Based Tracking Group wore the tracker on 95 % of intervention days ; 96 % reported liking the website and 100 % liked the tracker . CONCLUSIONS The Fitbit was well accepted in this sample of women and associated with increased physical activity at 16 weeks . Leveraging direct-to-consumer mHealth technologies aligned with behavior change theories can strengthen physical activity interventions Background Forming specific health plans can help translate good intentions into action . Mobile text reminders can further enhance the effects of planning on behavior . Objective Our aim was to explore the combined impact of a Web-based , fully automated planning tool and mobile text reminders on intention to change saturated fat intake , self-reported saturated fat intake , and portion size changes over 4 weeks . Methods Of 1013 men and women recruited online , 858 were r and omly allocated to 1 of 3 conditions : a planning tool ( PT ) , combined planning tool and text reminders ( PTT ) , and a control group . All outcome measures were assessed by online self-reports . Analysis of covariance was used to analyze the data . Results Participants allocated to the PT ( meansat urated fat 3.6 , meancopingplanning 3 ) and PTT ( meansaturatedfat 3.5 , meancopingplanning 3.1 ) reported a lower consumption of high-fat foods ( F 2,571 = 4.74 , P = .009 ) and higher levels of coping planning ( F 2,571 = 7.22 , P < .001 ) than the control group ( meansat urated f at 3.9 , meancopingplanning 2.8 ) . Participants in the PTT condition also reported smaller portion sizes of high-fat foods ( mean 2.8 ; F 2 , 569 = 4.12 , P = .0 ) than the control group ( meanportions 3.1 ) . The reduction in portion size was driven primarily by the male participants in the PTT ( P = .003 ) . We found no significant group differences in terms of percentage saturated fat intake , intentions , action planning , self-efficacy , or feedback on the intervention . Conclusions These findings support the use of Web-based tools and mobile technologies to change dietary behavior . The combination of a fully automated Web-based planning tool with mobile text reminders led to lower self-reported consumption of high-fat foods and greater reductions in portion sizes than in a control condition . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 61819220 ; http://www.controlled-trials.com/IS RCT N61819220 ( Archived by WebCite at http://www.webcitation.org/63YiSy6R8 Implementation intentions planning in advance the situation in which one will act , have been proposed to be an effective self-regulatory technique for changing health behaviour . Encouraging people to receive text message reminders of their implementation intentions should enhance their strength and , thus , it was predicted that this combined approach would be particularly effective in increasing exercise . Participants ( N = 155 ) were r and omly allocated to one of five conditions ( implementation intentions and SMS , implementation intention , SMS or one of two control groups ) then completed self-report measures of exercise behaviour and motivation . Four weeks later , they responded to similar items . Results suggested that the combined intervention increased exercise frequency significantly more than the other strategies including the implementation intention group . It is proposed , therefore , that implementation intention effects can be enhanced via plan reminders Background : Self-care management has recently been suggested as an effective approach for secondary prevention of hypertension . This study was conducted to examine whether self-care behaviors could modulate blood pressure levels and also comparing the different training methods of self-care on patients ' adherence and controlling hypertension . Material s and Methods : This study was a prospect i ve r and omized controlled clinical trial , conducted on 180 hypertensive patients referring to four centers in Isfahan , Iran , between July and December 2013 . Block r and omization method were applied to divide eligible subjects into four equal groups , including group A in which the patients and their family were educated by cardiology resident about self-care behaviors through eight sessions , group B and group C were obtained self-care education through four pamphlets or eight short message services ( SMS ) , respectively and group D were obtained only usual care of hypertension without any training about self-care management . Results : Increasing vegetable intake and frequency of subject who took antihypertensive medication regularly and the reduction in the frequency of subjects who consumed high salt were significantly more in group A than the others ( P = 0.001 , P < 0.001 and P < 0.001 , respectively ) . The systolic and diastolic blood pressure had significantly more reduction in the group A than the other groups ( −8.18 ± 18.3 and − 3.89 ± 4.1 ; P < 0.001 , respectively ) . Conclusions : The self-care management education integration into the usual care along with using SMS and other educational material s may improve the efficient and effective adherence strategies BACKGROUND AND OBJECTIVES We have previously reported that supportive text messages delivered twice daily for three months have the potential to provide personalised support for patients with depression and co-morbid Alcohol Use Disorder ( AUD ) . In this study we report the six months outcomes . METHODS Participants ( n=54 ) with a DSM IV diagnosis of unipolar depression and AUD who completed an in-patient dual diagnosis treatment programme were r and omised to receive daily twice supportive text messages ( n=26 ) or a fortnightly thank you text message ( n=28 ) for three months . Primary outcome measures at six months were Beck 's Depression Inventory ( BDI-II ) scores and Cumulative Abstinence Duration ( CAD ) . TRIAL REGISTRATION NCT0137868 . RESULTS Unlike at three months , there was no statistically significant difference in six months BDI-II scores between the intervention ( n=24 ) and control ( n=24 ) groups ; 13.28 ( SD=8.7 ) vs. 15.08 ( SD=11.37 ) respectively after adjusting for the baseline scores , F ( 1 , 45)=0.192 , p=0.66 . There was also no significant difference in CAD between the text message group and the control group : 84.14 days ( 9.20 ) vs. 74.73 days ( 28.97 ) , t=1.422 , df=41 , p=0.16 . However , patients in the intervention group had significantly higher days to first drink compared to those in the control group : 119.9 ( 47.7 ) vs. 62.4 ( 44.9 ) , t=2.99 , df=22 , p=0.01 . LIMITATIONS Limitations of the study include the small sample size and the potential for loss of rater blinding . CONCLUSION The effects of supportive text message intervention were not sustained beyond the period that the patients were receiving the intervention OBJECTIVE Between 31 and 35 % of the college-aged population is overweight or obese , yet few weight loss trials for this population have been conducted . This study examined the feasibility , acceptability , and initial efficacy of a technology-based 8-week weight loss intervention among college students . DESIGN AND METHODS Students ( N = 52 ) were r and omly assigned to one of the three arms : Facebook ( n = 17 ) ; Facebook Plus text messaging and personalized feedback ( n = 18 ) ; Waiting List control ( n = 17 ) , with assessment s at 4 weeks and 8 weeks ( post-treatment ) . Participants were 20.47 ± 2.19 years old , 86.45 ± 17.11 kg , with a body mass index of 31.36 ± 5.3 kg/m(2 ) . Participants were primarily female ( 86.5 % ) , and the sample was racially diverse ( 57.7 % Caucasian , 30.8 % African American , 5.8 % Hispanic , and 5.7 % other races ) . RESULTS The primary outcome was weight loss after 8 weeks ( post-treatment ) ; 96.0 % of the participants completed this assessment . At 8 weeks , the Facebook Plus group had significantly greater weight loss ( -2.4 ± 2.5 kg ) than the Facebook ( -0.63 ± 2.4 kg ) and Waiting List ( -0.24 ± 2.6 kg ) ( both Ps < 0.05 ) . Weight change at 8 weeks was not significantly different between the Facebook and Waiting List groups . CONCLUSIONS Results show preliminary efficacy and acceptability of the two active intervention arms ( 97.0 % found the program helpful , 81.3 % found the videos/h and outs helpful , and 100 % would recommend the program to others ) . Results indicate the potential for an innovative weight loss intervention that uses technology platforms ( Facebook and text messaging ) that are frequently used and already integrated into the cultural life of college students BACKGROUND Brief interventions have the potential to reduce heavy drinking in young adults who present to the emergency department ( ED ) , but require time and re sources rarely available . Text-messaging ( TM ) may provide an effective way to collect drinking data from young adults after ED discharge as well as to provide immediate feedback and ongoing support for behavior change . The feasibility of screening young adults in the ED , recruiting them for a TM-based interventional trial , collecting weekly drinking data through TM , and the variance in drinking outcomes remains unknown . METHODS Young adults in 3 urban EDs ( n = 45 ; aged 18 to 24 years , 54 % women ) identified as hazardous drinkers by the Alcohol Use Disorders Identification Test-Consumption score were r and omly assigned to weekly TM-based feedback with goal setting ( Intervention ) , weekly TM-based drinking assessment s without feedback ( Assessment ) , or control . Participants in the Intervention group who reported ≥5 ( for men ) and ≥4 ( for women ) maximum drinks during any one 24-hour period were asked whether they would set a goal to reduce their drinking the following week . We describe the interaction with TM and goal setting . We also describe the heavy drinking days ( HDDs ) , drinks per drinking day ( DPDD ) using timeline follow-back procedure at baseline and 3 months . RESULTS We screened 109 young adults over 157 hours across 24 unique days and 52 ( 48 % ; 95 % CI 38 to 50 ) screened positive for hazardous drinking . Of these , 45 ( 87 % ; 95 % CI 74 to 94 ) met inclusion criteria , were enrolled and r and omized , and 6 ( 13 % ; 95 % CI 5 to 27 ) did not complete 3-month web-based follow-up ; 88 % ( 95 % CI 84 to 91 ) of weekly TM-based drinking assessment s were answered , with 77 % ( 95 % CI 58 to 90 ) of participants responding to all 12 weeks . Agreeing to set a goal was associated with a repeat HDD 36 % ( 95 % CI 17 to 55 ) of the time compared with 63 % ( 95 % CI 44 to 81 ) when not willing to set a goal . At 3 months , participants that were exposed to the TM-based intervention had 3.4 ( SD 5.4 ) fewer HDDs in the last month and 2.1 ( SD 1.5 ) fewer DPDD when compared to baseline . CONCLUSIONS TM can be used to assess drinking in young adults and can deliver brief interventions to young adults discharged from the ED . TM-based interventions have the potential to reduce heavy drinking among young adults but larger studies are needed to establish efficacy OBJECTIVE To determine the effect of mobile phone intervention on HbA1c in type-2 Diabetes Mellitus ( DM ) patients living in rural areas of Pakistan . STUDY DESIGN R and omized controlled trial . PLACE AND DURATION OF STUDY Department of Endocrinology , Liaquat National Hospital , Karachi , from December 2013 to June 2014 . METHODOLOGY A total of 440 patients in intervention and control groups were enrolled . All patients between 18 - 70 years of age , residing in rural areas of Pakistan , HbA1c ³ 8.0 % and having personal functional mobile phone were included . The intervention group patients were called directly on mobile phone after every 15 days for a period of 4 months . They were asked about the self-monitoring blood glucose , intake of medications , physical activity , healthy eating and were physically examined after 4 months . However , the control group was examined initially and after 4 months physically in the clinic and there were no mobile phone contacts with these patients . RESULTS Patients in intervention group showed improvement ( p < 0.001 ) in following diet plan from 17.3 % at baseline to 43.6 % at endline , however , the control group showed insignificant increase ( p=0.522 ) from 13.6 % at baseline to 15.9 % at endline . Intervention group ( RR = 2.71 , 95 % CI = 1.18 - 6.40 ) showed significant positive association with normalization of HbA1c levels . The relationship was adjusted for age , gender , socio-economic status , ethnicity , education , hypertension , medication , BMI , diet , LDL levels and physical activity . Dietary restriction and low LDL levels also showed significant associations with reduced HbA1c levels on multivariate analysis . CONCLUSION Mobile phone technology in rural areas of Pakistan was helpful in lowering HbA1c levels in intervention group through direct communication with the diabetic patients . Lowering LDL and following diabetic diet plan can reduce HbA1c in these patients and help in preventing future complications We tested the feasibility and effectiveness of an alcohol counseling intervention delivered via personalized text messages for college students with problem alcohol use . College students aged 18–23 completed online substance use and mental health question naires that served as a screening tool for problem alcohol use . We invited students who screened positive to be r and omized to intervention ( n = 8) or control groups ( n = 10 ) and assessed them at 1 month after they received their last text message . The intervention group received between four and six text messages daily for 4 days that required brief participant responses during the week following the web-based baseline assessment . Participants in the intervention group could also request booster texts for additional support . We personalized all texts , using data collected at baseline . Using a repeated measures ANOVA , we found that compared to the control group , the intervention group increased in readiness to change from baseline to follow-up ( p < .01 ) . Other promising trends were an increase in the intervention relative to the control group ’s confidence in their ability to change drinking behavior , and an increase in intentions to reduce alcohol use . These exploratory results indicate that the automated texting program we developed works well with college students and that text messaging as a means to deliver preventive interventions is a promising delivery platform INTRODUCTION To address the lack of smoking cessation programs available to young adults , Stop My Smoking ( SMS ) USA , a text messaging-based smoking cessation program , was developed and pilot tested . METHODS This was a two-arm r and omized controlled trial with adaptive r and omization ( arms were balanced by sex and smoking level [ heavy vs. light ] ) , conducted nationally in the United States . One hundred sixty-four 18- to 25-year-old daily smokers who were seriously thinking about quitting in the next 30 days were r and omized to either ( a ) the 6-week SMS USA intervention ( n = 101 ) or ( b ) an attention-matched control group aim ed at improving sleep and physical activity ( n = 63 ) . The main outcome measure was 3-month continuous abstinence , verified by a significant other . Participants but not research ers were blinded to study arm allocation . RESULTS Based upon intent-to-treat analyses , intervention participants ( 39 % ) were significantly more likely than control participants ( 21 % ) to have quit at 4 weeks postquit ( adjusted odds ratio [ aOR ] = 3.33 , 95 % confidence interval [ CI ] : 1.48 , 7.45 ) . Findings were not sustained at 3 months postquit , although rates in the SMS USA group were favored ( 40 % vs. 30 % , respectively ; aOR = 1.59 , 95 % CI : 0.78 , 3.21 ) . Subsequent analyses suggested that among intervention participants , SMS USA might be more influential for youth not currently enrolled in a higher education ( p = .06 ) . CONCLUSIONS Consistent with pilot studies , the sample was underpowered . Data suggest , however , that the SMS USA program affects smoking cessation rates at 4 weeks postquit . More research is needed before conclusions can be made about long-term impact . Identifying profiles of users for whom the program may be particularly beneficial also will be important OBJECTIVE The present study attempts to develop and pilot the feasibility and efficacy of a novel intervention using affective messages as a strategy to increase physical activity ( PA ) levels in adolescents . Design An exploratory pilot r and omized control trial was used to compare behaviour change over 2 weeks . A modified form of the International Physical Activity Question naire was used to assess PA behaviour . A total of 120 adolescents ( 16 - 19 years ) from 4 sixth forms in West Yorkshire completed the field-based study . METHOD Participants were r and omly assigned to one of three experimental conditions , or the control condition ( N=28 ) . Participants in experimental conditions received 1 short messaging service ( SMS ) text message per day over the 2 weeks , which included manipulations of either affective beliefs ( enjoyable/unenjoyable ; N=31 ) , instrumental beliefs ( beneficial/harmful ; N=30 ) , or a combination of these ( N=31 ) . Control participants received one SMS text message per week . Outcomes were measured at baseline and at the end of the 2 week intervention . RESULTS PA levels increased by the equivalent of 31.5 minutes of moderate ( four metabolic equivalent ) activity per week during the study . Main effects of condition ( p=.049 ) , and current physical activity level ( p=.002 ) were identified , along with a significant interaction between condition and current activity level ( p=.006 ) . However , when the sample was split at baseline into active and inactive participants , a main effect of condition remained for inactive participants only ( p=.001 ) . Post hoc analysis revealed that inactive participants who received messages targeting affective beliefs increased their activity levels significantly more than the instrumental ( p=.012 ) , combined ( p=.002 ) , and control groups ( p=.018 ) . CONCLUSION Strategies based on affective associations may be more effective for increasing PA levels in inactive individuals This study evaluated automated techniques including personalized normative feedback and protective behavioral strategies , for brief interventions intended to reduce peak alcohol concentrations in university students . After completing baseline assessment , a total of 1,678 hazardous-drinking consumers were r and omized to a single or a repeated Internet ( WEB ) or Interactive Voice Response ( IVR ) intervention , or to a control group ( Single WEB : 323 ; Single IVR : 329 ; Repeated WEB : 318 ; Repeated IVR : 334 ; Control group : 374 ) . At follow-up , six weeks after baseline , question naires were returned by 1,422 participants ( Single WEB : 277 ; Single IVR : 286 ; Repeated WEB : 259 ; Repeated IVR : 279 ; Control group : 321 ) . It was found that peak estimated BAC was reduced in the total group ( b -0.14 , 95 % confidence interval ( CI ) -0.023 ; -0.005 ) , in the total ( b -0.17 , 95 % CI -0.027 ; -0.007 ) and single ( b -0.021 , 95 % CI -0.032 ; -0.011 ) WEB group , and in the total ( b -0.011 , 95 % CI -0.021 ; -0.015 ) and repeated ( b -0.012 , 95 % CI -0.023 ; -0.000 ) IVR groups , compared to controls . The reduction in peak estimated BAC was greater in the single WEB group compared to the single IVR group ( b -0.011 , 95 % CI -0.022 ; -0.000 ) . This study concluded that both WEB and IVR interventions have a small but significant effect in reducing heavy episodic drinking , which may be due to the relatively large sample size . Repeated intervention may be needed if delivered by IVR OBJECTIVE Text-messaging shows promise as a health intervention . This r and omized controlled trial evaluated a daily text-messaging weight loss intervention . METHODS Overweight and obese adults ( n=170 ) in California were r and omized to receive daily interactive and personally weight-relevant text-messages or monthly e-newsletters . Participants were measured at baseline , 6 and 12 months . Group differences were assessed in weight loss . Relation of text-messaging adherence to weight loss and change in pedometer steps was examined . RESULTS There were no group differences in weight loss over 6 ( 1.53 lb vs 3.72 lb ) or 12 months ( 2.27 lb vs 3.64 lb ; control vs intervention ) . Text-messaging adherence was moderately strong ( 60 - 69 % ) . Participants with greater adherence lost more weight at 6 ( p=.039 ) and 12 months ( p=.023 ) than those who were less adherent . Intervention participants ' steps increased almost 3000 steps/day over time ( p<.05 ) , and higher step counts were associated with greater weight loss ( p<.05 ) . Text-messaging satisfaction was moderate to high , and pedometer-related satisfaction was associated with greater weight loss ( p<.05 ) . CONCLUSIONS Although text-messaging had no effect on weight , adherence was associated with improvement in weight-related behaviors and weight outcomes . Text-messages could be a useful adjunct to weight loss treatments Abstract We investigated the effectiveness of a workplace intervention program that utilized self-monitoring of daily salt excretion by an electronic salt sensor and sent personalized e-mail advice via cellular phone . Forty-one hypertensive male workers were assigned to intervention and control groups , then counseled together . Intervention group members were asked to measure daily salt excretion and received e-mail advice . After 4 weeks , a greater decrease of blood pressure ( BP ) was observed in the intervention group , with significant reductions to daily salt excretion and home BP . The new intervention program is considered useful for BP control among hypertensive workers Background Previous interventions have shown promising results using theory-based podcasts to deliver a behavioral weight-loss intervention . Objective The objective of our study was to examine whether a combination of podcasting , mobile support communication , and mobile diet monitoring can assist people in weight loss . Methods In this 6-month , minimal contact intervention , overweight ( n = 96 , body mass index 32.6 kg/m2 ) adults were recruited through television advertisements and email listservs and r and omly assigned to Podcast-only or Podcast+Mobile groups . Both groups received 2 podcasts per week for 3 months and 2 minipodcasts per week for months 3–6 . In addition to the podcasts , the Podcast+Mobile group was also instructed to use a diet and physical activity monitoring application ( app ) on their mobile device and to interact with study counselors and other participants on Twitter . Results Weight loss did not differ by group at 6 months : mean –2.7 % ( SD 5.6 % ) Podcast+Mobile , n = 47 ; mean –2.7 % ( SD 5.1 % ) Podcast , n = 49 ; P = .98 . Days/week of reported diet monitoring did not differ between Podcast+Mobile ( mean 2.3 , SD 1.9 days/week ) and Podcast groups ( mean 1.9 , SD 1.7 days/week ; P = .28 ) but method of monitoring did differ . Podcast+Mobile participants were 3.5 times more likely than the Podcast group to use an app to monitor diet ( P = .01 ) , whereas the majority of Podcast participants reported using the Web ( 14/41 , 34 % ) or paper ( 12/41 , 29 % ) . There were more downloads per episode in the Podcast+Mobile group ( 1.4/person ) than in the Podcast group ( 1.1/person ; P < .001 ) . The number of podcasts participants reported downloading over the 6-month period was significantly moderately correlated with weight loss in both the Podcast+Mobile ( r = –.46 , P = .001 ) and the Podcast ( r = –.53 , P < .001 ) groups . Podcast+Mobile participants felt more user control at 3 months ( P = .02 ) , but not at 6 months , and there was a trend ( P = .06 ) toward greater elaboration among Podcast+Mobile participants . There were significant differences in reported source of social support between groups . More Podcast participants relied on friends ( 11/40 , 28 % vs 4/40 , 10 % ; P = .045 ) whereas Podcast+Mobile participants relied on online sources ( 10/40 , 25 % vs 0/40 ; P = .001 ) . Conclusions Results confirm and extend previous findings showing a minimally intensive weight-loss intervention can be delivered via podcast , but prompting and mobile communication via Twitter and monitoring app without feedback did not enhance weight loss . Trial Registration Clinical trials.gov NCT01139255 ; http:// clinical trials.gov/ct2/show/NCT01139255 ( Archived by WebCite at http://www.webcitation.org/625OjhiDy Background : Obese adolescents are at risk for type 2 diabetes mellitus ( T2DM ) . Obesity interventions delivered through media , such as the web and text messages [ short message service ( SMS ) ] may be beneficial when targeting obese adolescents . Methods : A r and omized controlled trial , Pace-Internet for Diabetes Prevention Intervention ( PACEi-DP ) , compared three forms of an obesity intervention to usual care ( UC ) : ( a ) website only ( W ) ; ( b ) website , monthly group sessions , and follow-up calls ( WG ) ; and ( c ) website and SMS ( WSMS ) . Participants were overweight or obese adolescents at risk for T2DM ( n = 101 ; age 12–16 years ; mean body mass index ( BMI ) percentile = 97.6 ; 74.3 % Hispanic ) . In addition to the website , WSMS participants received SMS supporting intervention goals and behavioral strategies and communicated via SMS with a case manager . WG participants had additional group activities related to weight loss and received follow-up calls from a health coach . UC participants were given printed material s and encouraged to attend three initial group sessions . Repeated measures mixed model regression analyses tested treatment effects for anthropometric , behavioral , and behavioral change strategy outcomes . Results : There were no treatment effects for BMI , adiposity , physical activity , or diet at 12 months . Treatment effects were observed for sedentary behavior , with the W arm having a greater decrease in sedentary behavior ( 4.9 to 2.8 h/day ) than the UC arm ( p = .006 ) . Conclusion : Although not sufficient to produce weight loss , the combination of web intervention and group sessions with telephone follow-up yielded improvements in sedentary behavior and in the use of behavior change strategies expected to lead to behavior change BACKGROUND Physical inactivity is a major , potentially modifiable , risk factor for cardiovascular disease , cancer , and other chronic diseases . Effective , simple , and generalisable interventions that will increase physical activity in population s are needed . AIM To evaluate the effectiveness of a smartphone application ( app ) to increase physical activity in primary care . DESIGN AND SETTING An 8-week , open-label , r and omised controlled trial in rural , primary care in the west of Irel and . METHOD And roid smartphone users > 16 years of age were recruited . All participants were provided with similar physical activity goals and information on the benefits of exercise . The intervention group was provided with a smartphone app and detailed instructions on how to use it to achieve these goals . The primary outcome was change in physical activity , as measured by a daily step count between baseline and follow-up . RESULTS A total of 139 patients were referred by their primary care health professional or self-referred . In total , 37 ( 27 % ) were screened out and 12 ( 9 % ) declined to participate , leaving 90 ( 65 % ) patients who were r and omised . Of these , 78 provided baseline data ( intervention = 37 ; control = 41 ) and 77 provided outcome data ( intervention = 37 ; control = 40 ) . The mean daily step count at baseline for intervention and control groups was 4365 and 5138 steps per day respectively . After adjusting , there was evidence of a significant treatment effect ( P = 0.009 ) ; the difference in mean improvement in daily step count from week 1 to week 8 inclusive was 1029 ( 95 % confidence interval 214 to 1843 ) steps per day , favouring the intervention . Improvements in physical activity in the intervention group were sustained until the end of the trial . CONCLUSION A simple smartphone app significantly increased physical activity over 8 weeks in a primary care population Background There is growing interest in the use of information communication technologies to treat obesity . An intervention delivered by smartphone could be a convenient , potentially cost-effective , and wide-reaching weight management strategy . Although there have been studies of texting-based interventions and smartphone applications ( apps ) used as adjuncts to other treatments , there are currently no r and omized controlled trials ( RCT ) of a st and -alone smartphone application for weight loss that focuses primarily on self-monitoring of diet and physical activity . Objective The aim of this pilot study was to collect acceptability and feasibility outcomes of a self-monitoring weight management intervention delivered by a smartphone app , compared to a website and paper diary . Methods A sample of 128 overweight volunteers were r and omized to receive a weight management intervention delivered by smartphone app , website , or paper diary . The smartphone app intervention , My Meal Mate ( MMM ) , was developed by the research team using an evidence -based behavioral approach . The app incorporates goal setting , self-monitoring of diet and activity , and feedback via weekly text message . The website group used an existing commercially available slimming website from a company called Weight Loss Re sources who also provided the paper diaries . The comparator groups delivered a similar self-monitoring intervention to the app , but by different modes of delivery . Participants were recruited by email , intranet , newsletters , and posters from large local employers . Trial duration was 6 months . The intervention and comparator groups were self-directed with no ongoing human input from the research team . The only face-to-face components were at baseline enrollment and brief follow-up sessions at 6 weeks and 6 months to take anthropometric measures and administer question naires . Results Trial retention was 40/43 ( 93 % ) in the smartphone group , 19/42 ( 55 % ) in the website group , and 20/43 ( 53 % ) in the diary group at 6 months . Adherence was statistically significantly higher in the smartphone group with a mean of 92 days ( SD 67 ) of dietary recording compared with 35 days ( SD 44 ) in the website group and 29 days ( SD 39 ) in the diary group ( P<.001 ) . Self-monitoring declined over time in all groups . In an intention-to-treat analysis using baseline observation carried forward for missing data , mean weight change at 6 months was -4.6 kg ( 95 % CI –6.2 to –3.0 ) in the smartphone app group , –2.9 kg ( 95 % CI –4.7 to –1.1 ) in the diary group , and –1.3 kg ( 95 % CI –2.7 to 0.1 ) in the website group . BMI change at 6 months was –1.6 kg/m2 ( 95 % CI –2.2 to –1.1 ) in the smartphone group , –1.0 kg/m2 ( 95 % CI –1.6 to –0.4 ) in the diary group , and –0.5 kg/m2 ( 95 % CI –0.9 to 0.0 ) in the website group . Change in body fat was –1.3 % ( 95 % CI –1.7 to –0.8 ) in the smartphone group , –0.9 % ( 95 % CI –1.5 to –0.4 ) in the diary group , and –0.5 % ( 95 % CI –0.9 to 0.0 ) in the website group . Conclusions The MMM app is an acceptable and feasible weight loss intervention and a full RCT of this approach is warranted . Trial Registration Clinical Trials.gov NCT01744535 ; http:// clinical trials.gov/ct2/show/NCT01744535 ( Archived by WebCite at http://www.webcitation.org/6FEtc3PVB BACKGROUND Today 's generation of young adults are gaining weight faster than their parents ; however , there remains insufficient evidence to inform interventions to prevent this weight gain . Mobile phones are a popular means of communication that may provide a convenient , inexpensive means to deliver health intervention programmes . This pilot study aim ed to measure the effect of a 12-week mobile health ( mHealth ) intervention on body weight , body mass index and specific lifestyle behaviours addressed by the programme . METHODS University students and staff aged 18 - 35 years ( n = 51 ) were r and omised ( ratio 1 : 1 , intervention : control ) . Both groups received a printed diet booklet with instructions prepared by a dietitian . The intervention group also received Short Message Service ( SMS ) text messages ( four per week ) , e-mails ( four per week ) , and had access to smartphone applications and Internet forums . RESULTS Pre- to post-intervention , participants in the intervention group decreased their body weight [ mean ( SD ) ] [ -1.6 ( 2.6 ) kg ] , increased their light intensity activity [ 34 ( 35 ) min day(-1 ) ] and reported an increased vegetable ( 1.0 median serving day(-1 ) ) and decreased sugar-sweetened beverage intake [ -355 ( 836 ) mL week(-1 ) ] . Despite this , post-intervention changes in outcomes were not significantly different from controls . CONCLUSIONS The piloted mHealth programme provided some short-term positive changes in weight , nutrition and physical activity using a low cost , convenient delivery method for this population . However , changes were no different from those observed among controls . This might partly be explained by intervention participants ' low engagement with the programme , which is likely to require further modification to provide more regular , personalised , monitored support INTRODUCTION The objective of this study was to test the feasibility and acceptance of an intervention using text messaging ( short message service [ SMS ] ) for continuous individual support of smoking cessation in young adults . Additionally , the optimal feedback intensity was investigated , and short-term efficacy of the intervention was explored . METHODS In a cafeteria of the University of Greifswald , 575 visitors were screened for smoking status and usage of text messaging . From these , 194 persons who fulfilled the inclusion criteria of daily smoking and weekly usage of SMS were invited for participation in an SMS-based intervention . From these , 174 ( 90 % ) consented to participate . The participants were r and omly allocated to one of three study groups : ( a ) control condition without intervention , ( b ) intervention with one weekly SMS feedback ( 1SMS ) , or ( c ) intervention with three weekly SMS feedbacks ( 3SMS ) . In study groups ( b ) and ( c ) , individualized SMS feedbacks were sent to the participants weekly , based on data from the baseline assessment and a weekly SMS assessment of the stages of change according to the transtheoretical model . Program use and acceptance were compared between the two intervention groups differing in support intensity . An exploration of the short-term efficacy of the program was conducted by comparing the three study groups at the end of the 3-month intervention program on smoking variables . RESULTS The median number of replies to the weekly SMS assessment s was 12.5 in the 1SMS group and 13.0 in the 3SMS group ( not significant ) . The acceptance of the program did not differ between the intervention groups . At post assessment , no significant differences between the three study groups emerged on the examined smoking variables . DISCUSSION The high participation and retention rates suggest that SMS-based smoking cessation interventions are attractive for young adults . Support intensity did not affect the acceptance of the program . Longer follow-up periods and larger sample s are required to obtain conclusive results about the efficacy of this intervention approach BACKGROUND Smoking during pregnancy is the main preventable cause of poor birth outcomes . Improved methods are needed to help women to stop smoking during pregnancy . Pregnancy provides a compelling rationale for physical activity ( PA ) interventions as cessation medication is contraindicated or ineffective , and an effective PA intervention could be highly cost-effective . OBJECTIVE To examine the effectiveness and cost-effectiveness of a PA intervention plus st and ard behavioural support for smoking cessation relative to behavioural support alone for achieving smoking cessation at the end of pregnancy . DESIGN Multicentre , two-group , pragmatic r and omised controlled trial and economic evaluation with follow-up at the end of pregnancy and 6 months postnatally . R and omisation was stratified by centre and a computer-generated sequence was used to allocate participants using a 1 : 1 ratio . SETTING 13 hospitals offering antenatal care in the UK . PARTICIPANTS Women between 10 and 24 weeks ' gestation smoking five or more cigarettes a day before pregnancy and one or more during pregnancy . INTERVENTIONS Participants were r and omised to behavioural support for smoking cessation ( control ) or behavioural support plus a PA intervention consisting of supervised treadmill exercise plus PA consultations . Neither participants nor research ers were blinded to treatment allocation . MAIN OUTCOME MEASURES The primary outcome was self-reported , continuous smoking abstinence between a quit date and end of pregnancy , vali date d by expired carbon monoxide and /or salivary cotinine . Secondary outcomes were maternal weight , depression , birth outcomes , withdrawal symptoms and urges to smoke . The economic evaluation investigated the costs of the PA intervention compared with the control intervention . RESULTS In total , 789 women were r and omised ( n = 394 PA , n = 395 control ) . Four were excluded post r and omisation ( two had been enrolled twice in sequential pregnancies and two were ineligible and r and omised erroneously ) . The intention-to-treat analysis comprised 785 participants ( n = 392 PA , n = 393 control ) . There was no significant difference in the rate of abstinence at the end of pregnancy between the PA group ( 7.7 % ) and the control group ( 6.4 % ) [ odds ratio for PA group abstinence 1.21 , 95 % confidence interval ( CI ) 0.70 to 2.10 ] . For the PA group compared with the control group , there was a 33 % ( 95 % CI 14 % to 56 % ) , 28 % ( 95 % CI 7 % to 52 % ) and 36 % ( 95 % CI 12 % to 65 % ) significantly greater increase in self-reported minutes of moderate- and vigorous-intensity PA from baseline to 1 week , 4 weeks and 6 weeks respectively . Accelerometer data showed that there was no significant difference in PA levels between the groups . There were no significant differences between the groups for change in maternal weight , depression , withdrawal symptoms or urges to smoke . Adverse events and birth outcomes were similar between the groups except for there being significantly more caesarean births in the control group than in the PA group ( 28.7 % vs. 21.3 % ; p < 0.023 ) . The PA intervention was less costly than the control intervention by £ 35 per participant . This was mainly attributable to increased health-care usage in the control group . However , there was considerable statistical uncertainty around this estimate . CONCLUSIONS During pregnancy , offering an intervention combining supervised exercise and PA counselling does not add to the effectiveness of behavioural support for smoking cessation . Only 10 % of participants had PA levels accessed by accelerometer and it is , therefore , unclear whether or not the lack of an effect on the primary outcome is the result of insufficient increases in PA . Research is needed to identify the smoking population s most suitable for PA interventions and methods for increasing PA adherence . TRIAL REGISTRATION Current Controlled Trials IS RCT N48600346 . 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. 84 . See the NIHR Journals Library website for further project information BACKGROUND Text messaging has successfully supported smoking cessation . This study compares a mobile application with text messaging to support smoking cessation . MATERIAL S AND METHODS Young adult smokers 18 - 30 years old ( n = 102 ) participated in a r and omized pretest-posttest trial . Smokers received a smartphone application ( REQ-Mobile ) with short messages and interactive tools or a text messaging system ( onQ ) , managed by an expert system . Self-reported usability of REQ-Mobile and quitting behavior ( quit attempts , point-prevalence , 30-day point-prevalence , and continued abstinence ) were assessed in posttests . RESULTS Overall , 60 % of smokers used mobile services ( REQ-Mobile , 61 % , mean of 128.5 messages received ; onQ , 59 % , mean of 107.8 messages ) , and 75 % evaluated REQ-Mobile as user-friendly . A majority of smokers reported being abstinent at posttest ( 6 weeks , 53 % of completers ; 12 weeks , 66 % of completers [ 44 % of all cases ] ) . Also , 37 % ( 25%of all cases ) reported 30-day point-prevalence abstinence , and 32 % ( 22 % of all cases ) reported continuous abstinence at 12 weeks . OnQ produced more abstinence ( p<0.05 ) than REQ-Mobile . Use of both services predicted increased 30-day abstinence at 12 weeks ( used , 47 % ; not used , 20 % ; p = 0.03 ) . CONCLUSIONS REQ-Mobile was feasible for delivering cessation support but appeared to not move smokers to quit as quickly as text messaging . Text messaging may work better because it is simple , well known , and delivered to a primary inbox . These advantages may disappear as smokers become more experienced with new h and sets . Mobile phones may be promising delivery platforms for cessation services using either smartphone applications or text messaging OBJECTIVE Lifestyle programs can reduce the level of overweight in children ; however , maintenance results and adherence to treatment are difficult to achieve . New technologies , such as the Short Message Service ( SMS ) , might be a promising tool for enhancing interventions . The effect of an SMS approach aim ed at improving treatment results and reducing dropout rates in a pediatric lifestyle intervention , is explored . METHOD Overweight and obese children ( N = 141 ; age 7 - 12 years ) participating in a lifestyle program were r and omly assigned to an intervention group receiving an SMS Maintenance Treatment ( SMSMT ) for 38 weeks ( n = 73 ) or to a control group receiving no SMSMT ( n = 68 ) . Children were asked to send weekly self-monitoring data on exercise , eating behavior , and emotional well-being . In return , they received tailored feedback messages . A differential decrease in BMI was analyzed with repeated measures ANOVA and dropout with logistic regression analysis . RESULTS We found no significant difference in BMI decrease between the two groups after 12 months ; however , we showed that the SMSMT group had 3.25 times less probability of dropping out after 1 year ( p = .01 ) than controls . In the first 3 months of SMSMT , the SMSMT completers sent 0.80 SMSs per week , which reduced to 0.50 SMSs in the final 3 months . Younger children sent more SMSs ( p = .03 ) . CONCLUSIONS These results indicate that SMSMT is effective in reducing dropout rates from a pediatric lifestyle intervention . Future research should examine the effectiveness of SMSMT on weight management and related psychosocial variables Aim : To conduct a pilot r and omised controlled trial of mobile phone-based smoking cessation support intervention for the UK population . Design : R and omised controlled trial ( txt2stop ) . Setting : Community . Participants : 200 participants responding to radio , poster and leaflet-based promotions regarding the trial . Main outcome measures : The response rate for the outcome measures planned for the main trial . Participants ’ qualitative responses to open-ended questions about the intervention content . Secondary outcomes were the outcomes planned for the main trial including the point prevalence of self-reported smoking at 4 weeks and pooled effect estimate for the short-term results for the STOMP and txt2stop trials . Results : The response rate at 4 weeks was 96 % and at 6 months was 92 % . The results at 4 weeks show a doubling of self-reported quitting relative risk ( RR ) 2.08 ( 95 % CI 1.11 to 3.89 ) , 26 % vs 12 % . The pooled effect estimate combining txt2stop and a previous New Zeal and trial in the short term is RR 2.18 ( 95 % CI 1.79 to 2.65 ) . Conclusions : Mobile phone-based smoking cessation is an innovative means of delivering smoking cessation support , which doubles the self-reported quit rate in the short term . It could represent an important , but as yet largely unused , medium to deliver age-appropriate public health measures . The long-term effect of this mobile phone-based smoking cessation support will be established by a large r and omised controlled trial currently in recruitment AIMS To test the population impact of offering automated smoking cessation interventions via the internet and /or by mobile phone . DESIGN Pragmatic r and omized controlled trial with five conditions : offer of ( i ) minimal intervention control ; ( ii ) QuitCoach personalized tailored internet-delivered advice program ; ( iii ) onQ , an interactive automated text-messaging program ; ( iv ) an integration of both QuitCoach and onQ ; and ( v ) a choice of either alone or the combined program . SETTING Australia , via a mix of internet and telephone contacts . PARTICIPANTS A total of 3530 smokers or recent quitters recruited from those interested in quitting , and seeking self-help re sources ( n = 1335 ) or cold-contacted from internet panels ( n = 2195 ) . MEASUREMENTS The primary outcome was self-report of 6 months sustained abstinence at 7 months post-recruitment . FINDINGS Only 42.5 % of those offered one of the interventions took it up to a minimal level . The intervention groups combined had a non-significantly higher 6-month sustained abstinence rate than the control [ odds ratio ( OR ) = 1.48 ; 95 % confidence interval ( CI ) : 0.98 - 2.24 ] ( missing cases treated as smokers ) , with no differences between the interventions . Among those who used an intervention , there was a significant overall increase in abstinence ( OR = 1.95 ; CI : 1.04 - 3.67 ) , but not clearly so when analysing only cases with reported outcomes . Success rates were greater among those recruited after seeking information compared to those cold-contacted . CONCLUSIONS Smokers interested in quitting who were assigned r and omly to an offer of either the QuitCoach internet-based support program and /or the interactive automated text-messaging program had non-significantly greater odds of quitting for at least 6 months than those r and omized to an offer of a simple information website BACKGROUND Helping patients control obesity remains a clinical challenge for internists , and African Americans experience obesity rates higher than other racial/ethnic groups . PURPOSE To investigate whether a behavioral theory-based mobile health intervention would enhance weight loss when added to st and ard care among overweight/obese African American adults . METHODS A r and omized controlled trial of 124 adults recruited from Baltimore-area African American churches . Participant follow-up ended March 2013 . Participants were r and omized to st and ard care ( included one-on-one counseling sessions with a dietitian and a physician ) or st and ard care plus daily tailored text messages for 6 months . Text messages were delivered in phases : preparation , reinforcement of participant-selected diet and exercise goals , reflection , goal integration , weight loss methods , and maintenance . There were follow-up visits at 3 , 6 , and 12 months . Primary outcome was weight change from baseline to end-intervention at 6 months . Secondary outcomes included weight change at 3 months , engagement , and satisfaction with the intervention . RESULTS Sixty-three participants were r and omized to the mobile health intervention and 61 to st and ard-care control . Weights were collected in-window for 45 ( 36.3 % ) at 3 months and 51 ( 41.1 % ) at 6 months . Mean weight loss at 3 months was 2.5 kg greater in the intervention group compared with st and ard care ( 95 % confidence interval [ CI ] , -4.3 to -0.6 ; P < .001 ) , and 3.4 kg greater ( 95 % CI , -5.2 to -1.7 ; P = .001 ) at 6 months . Degree of engagement with messages was correlated with weight loss . CONCLUSIONS While attrition was high , this study supports a tailored , interactive text-message intervention to enhance weight loss among obese African-American adults STUDY OBJECTIVE Opportunistic brief in-person emergency department ( ED ) interventions can be effective at reducing hazardous alcohol use in young adult drinkers , but require re sources frequently unavailable . Mobile telephone text messaging ( short message service [ SMS ] ) could sustainably deliver behavioral support to young adult patients , but efficacy remains unknown . We report 3-month outcome data of a r and omized controlled trial testing a novel SMS-delivered intervention in hazardous-drinking young adults . METHODS We r and omized 765 young adult ED patients who screened positive for past hazardous alcohol use to one of 3 groups : SMS assessment s+feedback ( SA+F ) intervention who were asked to respond to drinking-related queries and received real-time feedback through SMS each Thursday and Sunday for 12 weeks ( n=384 ) , SMS assessment s ( SA ) who were asked to respond to alcohol consumption queries each Sunday but did not receive any feedback ( N=196 ) , and a control group who did not participate in any SMS ( n=185 ) . Primary outcomes were self-reported number of binge drinking days and number of drinks per drinking day in the past 30 days , collected by Web-based timeline follow-back method and analyzed with regression models . Secondary outcomes were the proportion of participants with weekend binge episodes and most drinks consumed per drinking occasion during 12 weekends , collected by SMS . RESULTS With Web-based data , there were decreases in the number of self-reported binge drinking days from baseline to 3 months in the SA+F group ( -0.51 [ 95 % confidence interval { CI } -0.10 to -0.95 ] ) , whereas there were increases in the SA group ( 0.90 [ 95 % CI 0.23 to 1.6 ] ) and the control group ( 0.41 [ 95 % CI -0.20 to 1.0 ] ) . There were also decreases in the number of self-reported drinks per drinking day from baseline to 3 months in the SA+F group ( -0.31 [ 95 % CI -0.07 to -0.55 ] ) , whereas there were increases in the SA group ( 0.10 [ 95 % CI -0.27 to 0.47 ] ) and the control group ( 0.39 [ 95 % CI 0.06 to 0.72 ] ) . With SMS data , there was a lower mean proportion of SA+F participants reporting a weekend binge during 12 weeks ( 30.5 % [ 95 % CI 25 % to 36 % ) compared with the SA participants ( 47.7 % [ 95 % CI 40 % to 56 % ] ) . There was also a lower mean drinks consumed per weekend during 12 weeks in the SA+F group ( 3.2 [ 95 % CI 2.6 to 3.7 ] ) compared to the SA group ( 4.8 [ 95 % CI 4.0 to 5.6 ] ) . CONCLUSION A text message intervention can produce small reductions in self-reported binge drinking and the number of drinks consumed per drinking day in hazardous-drinking young adults after ED discharge OBJECTIVE To examine acceptability , attrition , adherence , and preliminary efficacy of mobile phone short message service ( SMS ; text messaging ) for monitoring healthful behaviors in children . DESIGN All r and omized children received a brief psychoeducational intervention . They then either monitored target behaviors via SMS with feedback or via paper diaries ( PD ) or participated in a no-monitoring control ( C ) for 8 weeks . SETTING University of North Carolina at Chapel Hill . PARTICIPANTS Fifty-eight children ( age 5 - 13 ) and parents participated ; 31 completed ( SMS : 13/18 , PD : 7/18 , C : 11/22 ) . INTERVENTION Children and parents participated in a total of 3 group education sessions ( 1 session weekly for 3 weeks ) to encourage increasing physical activity and decreasing screen time and sugar-sweetened beverage consumption . MAIN OUTCOME MEASURES Treatment acceptability , attrition , and adherence to self-monitoring . ANALYSIS Descriptive statistics and nonparametric tests were used to analyze differences across time and group . RESULTS Children in SMS had somewhat lower attrition ( 28 % ) than both PD ( 61 % ) and C ( 50 % ) , and significantly greater adherence to self-monitoring than PD ( 43 % vs 19 % , P < .02 ) . CONCLUSIONS AND IMPLICATION S Short message service may be a useful tool for self-monitoring healthful behaviors in children , although the efficacy of this approach needs further study . Implication s suggest that novel technologies may play a role in improving health BACKGROUND Studies have shown self-monitoring can modify health behaviors , including physical activity ( PA ) . This study tested the utility of a wearable sensor/device ( Fitbit ( ® ) One ™ ; Fitbit Inc. , San Francisco , CA ) and short message service ( SMS ) text-messaging prompts to increase PA in overweight and obese adults . MATERIAL S AND METHODS Sixty-seven adults wore a Fitbit One tracker for 6 weeks ; half were r and omized to also receive three daily SMS-based PA prompts . The Fitbit One consisted of a wearable tracker for instant feedback on performance and a Web site/mobile application ( app ) for detailed summaries . Outcome measures were objective ly measured steps and minutes of PA by intensity using two accelerometers : Actigraph ™ ( Pensacola , FL ) GT3X+ ( primary measure ) at baseline and Week 6 and Fitbit One ( secondary measure ) at baseline and Weeks 1 , 2 , 3 , 4 , 5 , and 6 . RESULTS Mixed-model repeated- measures analysis of primary measures indicated a significant within-group increase of + 4.3 ( st and ard error [SE]=2.0 ) min/week of moderate- to vigorous-intensity PA ( MVPA ) at 6-week follow-up ( p=0.04 ) in the comparison group ( Fitbit only ) , but no study group differences across PA levels . Secondary measures indicated the SMS text-messaging effect lasted for only 1 week : the intervention group increased by + 1,266 steps ( SE=491 ; p=0.01 ) , + 17.8 min/week MVPA ( SE=8.5 ; p=0.04 ) , and + 38.3 min/week total PA ( SE=15.9 ; p=0.02 ) compared with no changes in the comparison group , and these between-group differences were significant for steps ( p=0.01 ) , fairly/very active minutes ( p<0.01 ) , and total active minutes ( p=0.02 ) . CONCLUSIONS These data suggest that the Fitbit One achieved a small increase in MVPA at follow-up and that the SMS-based PA prompts were insufficient in increasing PA beyond 1 week . Future studies can test this intervention in those requiring less help and /or test strategies to increase participants ' engagement levels |
13,540 | 11,279,757 | Treatment provided a significant reduction in albumin excretion rate in both insulin dependent diabetes mellitus and non insulin dependent diabetes mellitus .
Treatment with either captopril , enalapril or lisinopril reduced albumin excretion rate in comparison with control patients .
A significantly greater lowering of blood pressure was experienced by initially normotensive patients in the angiotensin converting enzyme inhibitor than in the placebo group .
Average glycosylated haemoglobin fell a little in the treated patients and rose in the controls , the difference being just significant .
The difference in changes in glomerular filtration rate did not reach statistical significance .
REVIEW ER 'S CONCLUSIONS Inhibition of angiotensin converting enzyme can arrest or reduce the albumin excretion rate in microalbuminuric normotensive diabetics , as well as reduce or prevent an increase in blood pressure .
But , given the drop in blood pressure in patients on angiotensin converting enzyme inhibitors , it is not certain that the reduction of albumin excretion rate is due to a separate renal effect .
A direct link with postponement of end-stage renal failure has not been demonstrated .
There appear to be no substantial side effects | OBJECTIVES To examine whether the progression of early diabetic renal disease to end-stage renal failure may be slowed by the use of angiotensin converting enzyme inhibitors for reasons other than their antihypertensive properties , so that they have value in the treatment of normotensive diabetics with microalbuminuria . | OBJECTIVE --To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy ( albuminuria greater than 300 mg/24h ) . DESIGN --Open r and omised controlled study of four years ' duration . SETTING --Outpatient diabetic clinic in tertiary referral centre . PATIENTS --44 normotensive ( mean blood pressure 127/78 ( SD 12/10 ) mm Hg ) insulin dependent diabetic patients with persistent microalbuminuria ( 30 - 300 mg/24h ) . INTERVENTIONS --The treatment group ( n = 21 ) was initially given captopril ( 25 mg/24 h ) . The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months . The remaining 23 patients were left untreated . MAIN OUTCOME MEASURES --Albuminuria , kidney function , development of diabetic nephropathy ( albuminuria greater than 300 mg/24 h ) , and arterial blood pressure . RESULTS -- Clinical and laboratory variables were comparable at baseline . Urinary excretion of albumin was gradually reduced from 82 ( 66 - 106 ) to 57 ( 39 - 85 ) mg/24 h ( geometric mean ( 95 % confidence interval ) ) in the captopril treated group , whereas an increase from 105(77 - 153 ) to 166 ( 83 - 323 ) mg/24 h occurred in the control group ( p less than 0.05 ) . Seven of the untreated patients progressed to diabetic nephropathy , whereas none of the captopril treated patients developed clinical overt diabetic nephropathy ( p less than 0.05 ) . Systemic blood pressure , glomerular filtration rate , haemoglobin A1c concentration , and urinary excretion of sodium and urea remained practically unchanged in the two groups . CONCLUSIONS --The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria Recent studies utilizing converting enzyme inhibitors ( CEI ) in diabetic rats document reductions in both renal hypertrophy and albuminuria . Four separate clinical studies in normotensive patients with diabetes demonstrate reduction of microalbuminuria with CEIs independent of blood pressure reduction . The present pilot study examines the results of reducing an elevated glomerular filtration rate on changes in renal size and microalbuminuria in normotensive , hyperfiltering insulin-dependent diabetic ( IDDM ) patients . Fifteen IDDM patients were r and omized to either placebo or the CEI , lisinopril . Dosage of lisinopril was titrated over 3 months to reduce glomerular filtration rate ( GFR ) to < or = 2.33 mL/sec . Evaluation at 18 months demonstrated the lisinopril group had a marked reduction in renal size ( 16.9 + /- 1.1 , baseline versus 12.8 + /- 0.9 cm , 18 months ; p < 0.05 ) and microalbuminuria ( 92 + /- 11 micrograms/min , baseline versus 23 + /- 26 micrograms/min , 18 months ; p < 0.05 ) . No change in renal size was noted in the placebo group ( 15.4 + /- 0.8 , baseline versus 14.9 + /- 0.7 cm , 18 months ; NS ) and albuminuria increased ( 118 + /- 15 micrograms/min , baseline versus 293 + /- 32 micrograms/min , 18 months ; p < 0.05 ) . Mean arterial pressure at 18 months was significantly lower in the lisinopril group compared to placebo ( 102 + /- 4 , placebo versus 87 + /- 6 mm Hg , CEI , p < 0.05 ) . This study supports previous animal studies that document reductions in both microalbuminuria and renal size by a CEI . The overall impact of these findings on preservation of renal function can not be assessed , however , in this short-term study STUDY OBJECTIVE --To assess the effectiveness of inhibition of angiotensin converting enzyme in preventing diabetic nephropathy . DESIGN --R and omised follow up study of normotensive diabetics with persistent microalbuminuria ( 30 - 300 mg/24 hours ) treated with enalapril or its matched placebo for one year . Double blind for first six months , single blind for last six months . SETTING --Diabetic clinic in tertiary referral centre . PATIENTS --Treatment group and placebo group each comprised 10 normotensive diabetics with persistent microalbuminuria . INTERVENTIONS --Treatment group was given enalapril 20 mg daily and controls matched placebo . Patients were given antihypertensive treatment after one year . END POINT -- Albumin excretion , arterial pressure , and renal function . MAIN RESULTS --In last three months of trial three of 10 patients taking placebo had diabetic nephropathy ( albumin excretion greater than 300 mg/24 hours ) . No patients taking enalapril developed nephropathy and five showed normal albumin excretion ( less than 30 mg/24 hours ) ( p = 0.005 , Mann-Whitney test ) . Mean arterial pressure was reduced by enalapril throughout study ( p less than 0.005 ) but increased linearly with placebo ( p less than 0.05 ) . Albumin excretion decreased linearly with enalapril but not placebo . An increase in albumin excretion with placebo was positively related to the increase in mean arterial pressure ( r = 0.709 , p less than 0.05 , Spearman 's rank test ) . With enalapril total renal resistances and fractional albumin clearances improved progressively ( time effect , p = 0.0001 ) . CONCLUSION --Inhibition of angiotensin converting enzyme prevents development of nephropathy in normotensive diabetics with persistent microalbuminuria . This may be due to reduction in intraglomerular pressure and to prevention of increased systemic blood pressure . Future studies should compare long term effects of inhibitors of converting enzyme with other antihypertensive drugs The effect of early aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospect ively in ten insulin-dependent diabetics ( mean age 29 years ) . During the mean pretreatment period of 29 ( range 23 - 38 ) months the glomerular filtration rate ( GFR ) decreased significantly and the urinary albumin excretion rate and arterial blood pressure rose significantly . During the 39 month ( range 28 - 48 ) period of antihypertensive treatment with metoprolol , hydralazine , and frusemide ( furosemide ) or thiazide , arterial blood pressure fell from 144/97 mm Hg ( mean of all pretreatment values ) to 128/84 mm Hg ( mean of all post-treatment values ) , urinary albumin excretion from 977 micrograms/min to 433 micrograms/min , and GFR from 80 to 62 ml/min/1 . 73 m2 . The rate of decline in GFR decreased from 0.91 ml/min/month before treatment to 0.39 ml/min/month ( range 0.08 to 0.68 ml/min/month ) during treatment The beneficial effect of long-term treatment with an angiotensin-converting enzyme ( ACE ) inhibitor on urinary microalbumin excretion ( UAE ) and renal function was investigated in a 4 year , r and omized prospect i ve study in normotensive patients with non-insulin-dependent ( Type 2 ) diabetes mellitus . Sixty-two normotensive patients with Type 2 diabetes mellitus and microalbuminuria but normal renal function were r and omized to receive either enalapril 5 mg day-1 or no treatment . In the enalapril-treated patients , UAE was reduced from 115.4 + /- 80.1 to 95.6 + /- 61.7 mg 24 h-1 after 12 months ( p < 0.05 ) and to 75.3 + /- 44.8 mg 24 h-1 after 48 months ( p < 0.001 ) . In the untreated group , UAE increased slowly from 93.9 + /- 69.9 to 150.0 + /- 144.5 mg 24 h-1 after 48 months . No changes in creatinine clearance , blood pressure or HbA1C were seen in either group during the 4-year period . In normotensive Type 2 diabetic patients with early stage of diabetic microalbuminuria . This effect is long-lasting and probably independent of the antihypertensive action of the drug BACKGROUND Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries . Duration of diabetes , blood pressure values , and metabolic status are the major determinants of the course of nephropathy , and microalbuminuria is the hallmark of its onset . Angiotensin-converting enzyme inhibitors offer important renoprotection to hypertensive and normotensive patients with insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus . Our study extends previous observations for duration and the effect of angiotensin-converting enzyme inhibition on advanced nephropathy . METHODS Double-blinded ( first phase ) and open ( second phase ) r and omized controlled study of 7 years . Ninety-four normotensive patients with non-insulin-dependent diabetes mellitus whose serum creatinine levels were lower than 123.76 mumol/L ( 1.4 mg/dL ) and who had microalbuminuria ( 30 to 300 mg/24 h ) were given enalapril maleate , 10 mg/d , or placebo , for 5 years . For 2 more years they were followed up openly and given the choice to receive enalapril or no treatment . RESULTS In the enalapril-treated patients , albuminuria remained stable for 7 years . An increase from ( mean + /- SD ) 123 + /- 58 to 310 + /- 167 mg/24 h occurred in the untreated group after 5 years , and a further increase to ( mean + /- SD ) 393 + /- 223 mg/24 h occurred after 7 years . Reciprocal creatinine was unchanged in treated patients for 7 years ; in the untreated patients , the mean decline was 13 % at 5 years and 16 % at 7 years . Treatment with enalapril result ed in an absolute risk reduction of 42 % for nephropathy to develop during 7 years ( 95 % confidence interval , 15 % to 69 % ; P < .001 , Student 's t test ) . Glycosylated hemoglobin and body mass index remained unchanged . CONCLUSIONS Angiotensin-converting enzyme inhibition offers long-term protection against the development of nephropathy in normotensive patients with noninsulin-dependent diabetes mellitus who have microalbuminuria , and it stabilizes renal function in previously untreated patients with impaired renal function . Discontinuation of treatment results in renewed progression of nephropathy OBJECTIVE --To compare the effects of sodium depletion and of angiotensin I converting enzyme inhibition on microalbuminuria in insulin dependent diabetes . DESIGN --R and omised , double blind , double dummy parallel study of normotensive diabetic patients with persistent microalbuminuria ( 30 - 300 mg/24 h ) treated with enalapril or hydrochlorothiazide for one year after a three month , single blind placebo period . SETTING --Diabetic clinic in a tertiary referral centre . PATIENTS --10 diabetic patients with low microalbuminuria ( 30 - 99 mg/24 h ) and 11 with high microalbuminuria ( 100 - 300 mg/24 h ) . INTERVENTIONS --11 subjects ( six with low microalbuminuria , five with high microalbuminuria ) were given enalapril 20 mg plus placebo hydrochlorothiazide once daily and 10 ( four with low microalbuminuria , six with high microalbuminuria ) hydrochlorothiazide 25 mg plus placebo enalapril once daily . MAIN OUTCOME MEASURES --Monthly assessment of urinary albumin excretion and mean arterial pressure ; plasma active renin and aldosterone concentrations and renal function studies at 0 , 6 , and 12 months . RESULTS --Median urinary albumin excretion decreased from 59 ( range 37 - 260 ) to 38 ( 14 - 146 ) mg/24 h with enalapril and from 111 ( 33 - 282 ) to 109 ( 33 - 262 ) mg/24 h with hydrochlorothiazide ( analysis of variance , p = 0.0436 ) . During the last three months of treatment with enalapril five patients had persistent normoalbuminuria ( 2 - 3 times below 30 mg/24 h ) , five low microalbuminuria , and one high microalbuminuria ; in the hydrochlorothiazide group one had normoalbuminuria , three low microalbuminuria , and six high microalbuminuria ( chi 2 test = 6.7 ; p = 0.03 ) . Mean arterial pressure did not differ before ( 98 ( SD 7 ) with enalapril v 97 ( 9 ) mm Hg with hydrochlorothiazide ) or during treatment ( 88 ( 7 ) with enalapril v 90 ( 7 ) mm Hg with hydrochlorothiazide ( analysis of variance , p = 0.5263 ) ) . Glomerular filtration rate did not vary . The aldosterone to active renin ratio was decreased by angiotensin I converting enzyme inhibition and increased by sodium depletion , showing treatment efficacy . CONCLUSION --Angiotensin I converting enzyme inhibition by enalapril effectively reduces microalbuminuria in normotensive diabetic patients whereas hydrochlorothiazide is not effective . Changes in blood pressure and activity of the renin-angiotensin-aldosterone system may contribute to these different effects Ninety-four normotensive type II diabetics with normal renal function and microalbuminuria were r and omized to receive enalapril 10 mg/day or placebo and were followed for five years . In the patients treated by enalapril plasma creatinine values and albuminuria remained stable throughout the observation period . Their plasma total cholesterol decreased from an initial value of 245 + /- 27 mg/dl to mean study value of 236 + /- 29 mg/dl , and to a fifth year value of 232 + /- 27 mg/dl ( P < 0.001 ) . The changes in HDL cholesterol and triglyceride values were nonsignificant . In the placebo group there was a significant increase in albuminuria and a mean decline of 13 % in reciprocal creatinine values during the five years . Plasma total cholesterol increased from an initial mean value of 246 + /- 24 to a mean study value of 252 + /- 25 mg/dl , and to a fifth year mean value of 259 + /- 32 mg/dl ( P < 0.001 ) . There was a significant correlation between both initial and mean plasma total cholesterol values , and the decline in renal function and the rise in albuminuria in the placebo treated patients . This correlation persisted after stratification for blood pressure . Treatment with enalapril did not eliminate these correlations . Cholesterol may be an additional risk factor for diabetic nephropathy . ACE inhibitors may have a modest cholesterol lowering effect in diabetic patients mediated , in part , through the decline in albuminuria A prospect i ve self-controlled evaluation of renal function in non-insulin-dependent diabetic patients with early nephropathy , mild to moderate hypertension , and retinopathy was undertaken over a 1-year period . Thereafter , the effects of treatment with captopril on blood pressure , albumin excretion , and renal function were assessed . Glomerular filtration rate ( GFR ) , effective renal plasma flow ( ERPF ) , and systolic and diastolic blood pressures remained stable during the pretreatment period ; 24-h urinary protein excretion increased progressively from 0.79 + /- 0.13 to 1.23 + /- 0.18 g/24 h ( p < 0.05 ) ( mean + /- st and ard error ) . Captopril ( 25 mg b.i.d . ) for 3 months reduced systolic and diastolic blood pressures significantly ( p < 0.01 ) . Simultaneously , 24-h urinary protein excretion declined by 41 + /- 2.4 % , to 0.70 + /- 0.12 g/24 h ( p < 0.05 ) while GFR , ERPF , and fractional filtration demonstrated small but insignificant changes . Subsequently , increase in captopril to 50 mg b.i.d . for the remaining 6 months did not produce further significant changes in renal hemodynamics , blood pressure , or urinary protein excretion ( 0.48 + /- 0.10 g/24 h at the termination of the study ) . Non-insulin-dependent diabetic patients with early nephropathy and mild to moderate hypertension demonstrate a progressive increase in urinary protein excretion . Administration of captopril result ed in prompt control of hypertension and reversal of the increase in urinary protein excretion To evaluate the effect of enalapril on proteinuria , 16 normotensive type II diabetics with persistent proteinuria were studied . At r and om , the patients were allocated to enalapril ( 5 mg once a day ) or placebo , in a double-blind fashion , for 12 months . Blood pressure , heart rate , urinary albumin excretion , plasma renin activity and aldosterone , blood glucose , serum fructosamine , urine urea and body weight were checked monthly during the run-in period and every 2 months during the treatment period . The kidney function was studied at the beginning of the study and during the sixth and 12th months . Enalapril decreased urinary albumin excretion in our patients in the absence of any effect on blood pressure and kidney function . Our data may be interpreted on the basis of a direct vascular effect of enalapril that is probably related to a tissue mechanism consisting of reduced angiotensin formation , increased kinins , or both , or of other unknown factors Several studies have shown that long-term therapy with angiotensin-converting enzyme inhibitors may reduce urinary protein excretion and decrease the rate of progression of renal disease in patients with insulin-dependent diabetes mellitus more effectively than conventional antihypertensive drugs . Only few studies , however , have been performed in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . To compare the effects of captopril with more conventional drugs on proteinuria and progression of renal disease , we conducted a prospect i ve , 18-month study in 42 proteinuric ( > 500 mg/day ) NIDDM and , for comparison , in 31 nondiabetic patients with a variety of renal diseases ( NDRD ) . Twenty-four NIDDM patients were treated with captopril and 18 with conventional drugs . Eighteen NDRD patients received captopril , and 13 received conventional drugs . Baseline proteinuria and glomerular filtration rate ( GFR ) were not different among groups . The blood pressure decreased equally in all group of patients , irrespective of whether they received captopril or conventional drugs . Urinary protein excretion , however , decreased significantly only in NIDDM and NDRD patients treated with captopril . The GFR decreased only in patients treated with conventional drugs , but not in those treated with captopril . The rate of decline in GFR in NIDDM patients treated with captopril was significantly lower than in patients treated with conventional drugs . However , in NDRD patients treated with captopril , the rate of decline in GFR was not different from that in patients treated with conventional drugs . The reduction of urinary protein excretion was poorly correlated with changes in blood pressure or with changes in renal function and renal hemodynamics . Serum potassium increased significantly in patients treated with captopril . ( ABSTRACT TRUNCATED AT 250 WORDS |
13,541 | 26,888,294 | Conclusions Glutamate , β-EP , CGRP and NGF concentrations are altered in CSF and , except for NGF , also in blood of migraineurs . | Objective To perform a meta- analysis of migraine biomarkers in cerebrospinal fluid ( CSF ) and of corresponding blood concentrations . | To investigate the role of plasma calcitonin gene-related peptide ( CGRP ) in paediatric migraine , we prospect ively collected 134 blood sample s during or between attacks from 66 migraine , 33 non-migraine headache ( non-migraine ) and 22 non-headache patients , aged 4–18 years . Plasma CGRP concentrations were measured by enzyme-linked immunosorbent assay and disability by Pediatric MIgraine Disability ASsessment ( PedMIDAS ) question naire . Migraineurs had higher plasma CGRP levels than non-migraine patients ( P = 0.007 ) . The attack level was higher than the non-attack level in migraine ( P = 0.036 ) , but not in non-migraine , patients . This was also revealed in paired comparison ( n = 9 , P = 0.015 vs. n = 4 , P = 0.47 ) . Using a threshold of 55.1 pg/ml , the sensitivity of the attack level in predicting migraine was 0.81 , and specificity 0.75 . The PedMIDAS score tended to be higher in the high CGRP ( > 200 pg/ml , n = 7 ) group than in the low ( < 200 pg/ml , n = 33 ) group ( 26.07 vs. 19.32 , P = 0.16 ) using Mann – Whitney test . Plasma CGRP is useful for diagnosis in paediatric migraine Interictal serum levels of serotonin and plasma and mononuclear cell concentrations of β‐endorphin were measured in 20 juvenile patients ( 13 suffering from migraine without aura and 7 from episodic tension‐type headache ) before and after 3 months of L‐5‐hydroxytryptophan treatment ( 5 mg/ kg/day ) and compared with a control group of 17 headache‐free healthy subjects Plasma levels of beta‐endorphin ( BE ) , an endogenous opioid analgesic , are often reported as they relate to acute and chronic pain outcomes . However , little is known about what resting plasma BE levels might reveal about functioning of the endogenous opioid antinociceptive system . This study directly examined associations between resting plasma BE and subsequent endogenous opioid analgesic responses to acute pain in 39 healthy controls and 37 individuals with chronic low back pain ( LBP ) . Resting baseline levels of plasma BE were assessed . Next , participants received opioid blockade ( 8 mg naloxone i.v . ) or placebo in a double‐blind , r and omized , crossover design . Participants then underwent two acute pain stimuli : finger pressure ( FP ) pain and ischaemic ( ISC ) forearm pain . Blockade effects ( naloxone minus placebo pain ratings ) were derived to index endogenous opioid analgesic function . In placebo condition analyses for both pain stimuli , higher resting BE levels were associated with subsequently greater reported pain intensity ( p 's < 0.05 ) , with this effect occurring primarily in healthy controls ( BE × Participant Type interactions , p 's < 0.05 ) . In blockade effect analyses across both pain tasks , higher resting plasma BE predicted less subsequent endogenous opioid analgesia ( smaller blockade effects ; p 's < 0.05 ) . For the ISC task , these links were significantly more prominent in LBP participants ( BE × Participant Type Interactions , p 's < 0.05 ) . Results suggest that elevated resting plasma BE may be a potential biomarker for reduced endogenous opioid analgesic capacity , particularly among individuals with chronic pain . Potential clinical implication s are discussed & NA ; Although calcitonin gene‐related peptide ( CGRP ) has been shown to be elevated in jugular venous blood of adult migraineurs during acute migraine attacks , it remains unknown whether CGRP is increased outside of attacks in jugular or cubital venous blood . The aim of the present study was to compare interictal plasma levels of CGRP in adult migraine patients and in healthy controls . Twenty patients with a diagnosis of migraine with or without aura and 20 healthy controls were included . In blood from the cubital vein , CGRP levels were significantly higher in patients ( 75±8 pmol/l ( mean±SEM ) ) than in controls ( 49±3 pmol/l ) ( P=0.005 ) . The subgroup of patients suffering exclusively from migraine without aura ( n=14 ) also had significantly higher levels of CGRP ( 82±10 pmol/l ) than controls ( n=20 ; 49±3 pmol/l ) ( P=0.001 ) . The findings could not be explained by confounding factors such as age , sex or use of contraceptive pills . We therefore conclude that CGRP is increased in cubital venous blood of migraineurs outside of attack . It is hypothesized that this finding may reflect a long‐lasting or permanent abnormal neurogenic vascular control in patients with migraine The aim of the present study was to verify cerebrospinal fluid ( CSF ) levels of glial cell line-derived neurotrophic factor ( GDNF ) and somatostatin , both measured by sensitive immunoassay , in : 16 chronic migraine ( CM ) patients , 15 patients with an antecedent history of migraine without aura diagnosed as having probable chronic migraine ( PCM ) and probable analgesic-abuse headache ( PAAH ) , 20 patients affected by primary fibromyalgia syndrome ( PFMS ) , and 20 control subjects . Significantly lower levels of GDNF and somatostatin were found in the CSF of both CM and PCM + PAAH patients compared with controls ( GDNF = P < 0.001 , P < 0.002 ; somatostatin = P < 0.002 , P < 0.0003 ) , without significant difference between the two groups . PFMS patients , with and without analgesic abuse , also had significantly lower levels of both somatostatin and GDNF ( P < 0.0002 , P < 0.001 ) , which did not differ from those of CM and PCM + PAAH patients . A significant positive correlation emerged between CSF values of GDNF and those of somatostatin in CM ( r = 0.70 , P < 0.02 ) , PCM + PAAH ( r = 0.78 , P < 0.004 ) , and PFMS patients ( r = 0.68 , P < 0.008 ) . Based on experimental findings , it can be postulated that reduced CSF levels of GDNF and somatostatin in both CM and PCM + PAAH patients can contribute to sustained central sensitization underlying chronic head pain . The abuse of simple or combination analgesics does not seem to influence the biochemical changes investigated , which appear to be more strictly related to the chronic pain state , as demonstrated also for fibromyalgia & NA ; In nine women suffering from menstrual migraine ( MM ) , and in six healthy asymptomatic volunteers , plasma beta‐endorphin ( beta‐EP ) , growth hormone ( GH ) , norepinephrine ( NE ) , and 3‐methoxy‐4‐hydroxyphenylethyleneglycol ( MHPG ) concentrations were measured in response to clonidine ( 0.075 mg , i.v . ) stimulation . In MM patients clonidine testing was performed in both the early and the late luteal phases of the menstrual cycle . Premenstrual symptoms were prospect ively evaluated in the actual cycle using the Moos Menstrual Distress Question naire . beta‐EP ( after gel chromatography ) and GH were measured using radioimmunoassay . NE and MHPG were evaluated by HPLC using electrochemical detection . In both phases of the menstrual cycle clonidine significantly reduced NE and MHPG levels in MM patients and controls in a similar way . In MM patients beta‐EP and GH plasma levels were stimulated by clonidine only in the early luteal phase , whereas they remained unchanged when they were stimulated in the premenstrual period . In controls the response of both hormones was not affected by the menstrual cycle . The lack of hormonal response to clonidine in MM may suggest a postsynaptic alpha 2‐adrenoreceptor hyposensitivity during the premenstrual period . This demonstrates a transient vulnerability of the neuroendocrine/neurovegetative systems , and could thus be a factor facilitating the precipitation of both behavioral changes and migraine attacks BACKGROUND Pharmaceuticals with calcium- or sodium-channel-blocking activity have proven useful for migraine prophylaxis , and calcium channel , sodium transporter , and sodium channel gene mutations have been found in familial hemiplegic migraine . However , it is not known whether calcium or sodium homeostasis is altered in migraine . OBJECTIVE To compare levels of sodium , calcium , potassium , and magnesium in cerebrospinal fluid ( CSF ) and blood plasma between migraineurs and controls . METHODS We recruited 20 migraineurs without aura and 11 controls prospect ively , and studied migraineurs in sick ( MH(+ ) ) and well ( MH(- ) ) states . We collected lumbar CSF and venous blood plasma , quantified elements with ion-selective electrodes or colorimetry , and determined osmolality by depression of freezing point . We compared levels of Na(+ ) , Ca(2 + ) , K(+ ) , and Mg among and also within subjects who were studied in both MH(+ ) and MH(- ) states . RESULTS Mean CSF Na(+ ) levels were increased by 3 mmol/L in MH(+ ) compared with MH(- ) and by 4 mmol/L compared to controls ( P < 0.005 ) . In 4 subjects who were sample d in both MH(+ ) and MH(- ) states , mean CSF Na(+ ) concentration increased by 2 mmol/L in the MH(+ ) state compared with the MH(- ) state ( P < 0.05 ) . Simultaneous plasma Na(+ ) levels did not differ among the 3 clinical groups , nor did osmolality , total Ca and Ca(2 + ) , K(+ ) , and total Mg levels in CSF . CONCLUSIONS Compared to both controls and the MH(- ) state , CSF Na(+ ) concentration increased in MH(+ ) independently from other clinical or pharmacological fluctuations , CSF concentrations of Ca(2 + ) , Mg , and K(+ ) , and blood plasma Na(+ ) levels . These results implicate a deviation of Na(+ ) homeostasis in migraine . The modestly elevated extracellular Na(+ ) in MH(+ ) may cause the neural changes that underlie clinical features of migraine Neurotrophins , such as brain-derived neurotrophic factor ( BDNF ) and nerve growth factor ( NGF ) , have been implicated in the generation and modulation of pain . To investigate whether alterations in neurotrophin levels can be detected in subjects suffering from nociceptive disorders , such as primary headaches , we determined the peripheral ( platelet and plasma ) levels of BDNF and NGF in patients suffering from migraine , with or without aura , or cluster headache ( CH ) , in the interictal phase , and in healthy volunteers . All primary headaches patients studied showed significantly decreased platelet levels of BDNF ( migraine vs. controls P < 0.001 ; CH vs. controls P < 0.01 ) , while a selective reduction of platelet NGF was observed in migraine sufferers and not in CH patients compared with control subjects ( migraine vs. controls P < 0.001 ) . These changes were not accompanied by significant modifications of neurotrophin plasma levels . Our findings show for the first time that changes in peripheral levels of neurotrophines ( BDNF and NGF ) occur in patients suffering from different types of primary headaches , suggesting a potential involvement of BDNF and NGF in the pathophysiology of these disorders , and raising the possibility that differences in peripheral neurotrophins may help to distinguish migraine biologically from CH |
13,542 | 15,266,432 | This review did not find any suggestion that zuclopenthixol acetate is more or less effective in controlling aggressive acute psychosis , or in preventing adverse effects than intramuscular haloperidol , and neither seemed to have a rapid onset of action . | BACKGROUND Medication used for acute aggression in psychiatry must have rapid onset of effect , low frequency of administration and low levels of adverse effects .
Zuclopenthixol acetate is said to have these properties .
OBJECTIVES To estimate the clinical effects of zuclopenthixol acetate for the management of acute aggression or violence thought to be due to serious mental illnesses , in comparison to other drugs used to treat similar conditions . | Animal data suggest that a D1 antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect . This has led to the hypothesis that neuroleptics with D1 antagonistic activity should cause a better suppression of tardive dyskinesia ( TD ) and less rebound aggravation after withdrawal than pure D2 antagonists . In this study the effect of zuclopenthixol ( mixed D1/D2 antagonist ) and haloperidol ( D2 antagonist ) was evaluated in chronic psychotic patients with TD . Fifteen patients completed a r and omized crossover study with blind evaluation of TD and parkinsonism . The test medications , haloperidol and zuclopenthixol , caused a significant suppression of TD and a significant increase of parkinsonism . No significant differences between haloperidol and zuclopenthixol were observed . No TD aggravation was seen . The lack of differences between the mixed D1/D2 antagonist and a D2 antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD Zuclopenthixol acetate — a new injectable formulation with a duration of action of 2–3 days — was compared with conventional intramuscular and oral formulations of haloperidol and zuclopenthixol in the initial treatment of acutely disturbed , psychotic patients . The patients were stratified into 3 diagnostic categories : acute psychoses ( 48 patients ) , mania ( 22 patients ) , and exacerbation of chronic psychoses ( 73 patients ) . The patients were rated on the Brief Psychiatric Rating Scale ( BPRS ) , the Bech‐Rafaelsen Mania Rating Scale ( brmas ) ( only manic patients ) and globally on the Clinical Global Impression ( CGI ) . The study was an open , r and omized multicentre trial with a 6‐day treatment period . The zuclopenthixol acetate patients received 1–4 doses , the haloperidol patients 1–26 and the zuclopenthixol patients 1–22 doses . The assessment s on the CGI showed that all 3 treatments caused a clear reduction of the severity of illness scores in all 3 diagnostic categories , with no differences between treatments . The ratings of the acute and chronic psychotic patients on the BPRS also showed significant reductions in scores with no differences between treatments . All 3 treatments caused a rapid remission of symptoms on the BRMAS . Haloperidol induced hypokinesia in significantly more patients than zuclopenthixol acetate after 24 h. Later there were no significant differences between treatments . Zuclopenthixol acetate fulfils many desires for an amended neuroleptic formulation for the initial treatment of acutely disturbed psychotic patients OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas In an open clinical multi-centre trial carried out in five Danish psychiatric departments , patients suffering from acute psychosis including mania or exacerbation of chronic psychosis were given injections of 5 % zuclopenthixol acetate in ' Viscoleo ' . The object of the trial was to evaluate the treatment by means of a global assessment of the severity of the psychosis , the therapeutic effect and the side-effects . The results showed that the treatment was rapidly effective in reducing the severity of psychotic symptoms combined with an advantageous unspecific sedation . The side-effect profile was similar to that after other neuroleptics . Special attention should be paid , however , to a possible occurrence of acute dystonia which was observed particularly in young men with acute psychosis The aim of this study was to evaluate the efficacy and side effects of zuclopenthixol acetate compared with haloperidol in the management of the acutely disturbed schizophrenic patient . Suitable subjects diagnosed as having schizophreniform disorder or acute exacerbation of schizophrenia admitted to the psychiatric wards Hospital Kuala Lumpur were r and omised to receive either zuclopenthixol acetate or haloperidol . They were rated blind for three consecutive days using the Brief Psychiatric Rating Scale ( BPRS ) , Clinical Global Impression ( CGI ) and UKU Side Effects Scale . Apart from repeat injections of the same medication , no other anti-psychotic was given for the duration of the study . 50 subjects entered the study of which 44 completed . 23 were given zuclopenthixol acetate and 21 haloperidol . Both groups significantly reduced BPRS and CGI scores on all 3 days compared to the initial rating ( p < 0.001 ) . There was however no difference between the zuclopenthixol acetate and haloperidol group scores on all days ( p > 0.05 ) . More subjects on haloperidol than zuclopenthixol required more than 1 injection during the study . Both groups had minimal side effects . Zuclopenthixol acetate was effective in the management of the acutely disturbed schizophrenic BACKGROUND Case series and review s have suggested the effectiveness of zuclopenthixol acetate in the acute management of disturbed behaviour caused by serious mental illnesses . This review investigates the trial-based evidence for these suggestions . METHODS All r and omized clinical trials comparing zuclopenthixol acetate to other ' st and ard ' treatments for the acute management of those with serious mental illnesses were identified and , if possible , their results summated . RESULTS Six trials were identified . All had method ological problems and one did not meet the minimal method ological inclusion criteria . The summary data do not demonstrate that zuclopenthixol acetate is better than ' st and ard care ' for altering behaviour , decreasing the need for supplementary medication , avoiding side-effects , or postponing early discharge against medical advice . One trial , however , presented data that suggested an earlier , more intense level of sedation . CONCLUSIONS Recommendations of review s and open studies for the use of zuclopenthixol acetate in preference to ' st and ard ' treatments in the psychiatric emergency are not supported by evidence from r and omized controlled trials One hundred mentally retarded patients from five Finnish institutions took part in a double‐blind , double‐dummy 12‐week trial assessing the therapeutic effect of cis(Z)‐clopenthixol and haloperidol . Assessment s including CGI by psychiatrists and ward personnel as well as a 4‐item target symptom scale were done at weeks 0 , 4 , 8 , and 12 . Improvement was registered by the psychiatrists in 16 , 21 , and 24 cis(Z)‐clopenthixol patients and in 11 , 6 , and 7 haloperidol patients at weeks 4 , 8 , and 12 , respectively ‐ the difference between the two drugs being significant at weeks 8 and 12 . The ratings of CGI by the personnel and the 4‐item scale by the psychiatrists showed less improvements and no significant differences between the two drugs . While the overall impression of interference of patients ’ functioning by side‐effects were in the favour of haloperidol the number of single side effects increased more with haloperidol than with cis(Z)‐clopenthixol during the 12 weeks . Average doses administered at week 12 were 34 mg cis(Z)‐clopenthixol and 5 mg haloperidol Fifty-four hospitalized chronic schizophrenics were included in a double-blind controlled trial to assess the value of clopenthixol in treating [ See Table 4 in Source Pdf . ] such cases and compare its effects with those of chlorpromazine . Two rating scales were used to assess the patients clinical ly : a behavioural scale with items fairly objective and concrete , and an inferential one with items more " speculative " or " interpretative " . The patients were rated without medication and four weeks later with medication . Clopenthixol result ed in a change at the behavioural level . Chlorpromazine result ed in changes at the behavioural and inferential levels . No changes occurred with the placebo . Side-effects were not severe at therapeutically effective levels A double‐blind , r and omized , multi‐center , parallel‐group study was conducted in Finl and to compare the efficacy and safety of risperidone with zuclopenthixol in patients with acute exacerbations of schizophrenia or schizophreniform disorder . Ninety‐eight patients were r and omly assigned to treatment with risperidone ( n= 48 ) or zuclopenthixol ( n= 50 ) , in variable doses , for 6 weeks . The mean daily doses of risperidone and zuclopenthixol at the end of the trial were 8 mg and 38 mg respectively . Efficacy was assessed throughout by the Positive and Negative Syndrome Scale for schizophrenia and Clinical Global Impression . Safety assessment s included the Extrapyramidal Symptom Rating Scale , UKU Side‐Effect Rating Scale , vital signs , body weight and laboratory screening . The results indicate that risperidone is at least as effective as zuclopenthixol for the treatment of acute schizophrenic episodes , with a trend towards greater improvement in the overall severity of symptoms . The onset of action was significantly shorter with risperidone than with zuclopenthixol . Although the general tolerability of the two drugs was comparable , fewer patients experienced extrapyramidal symptoms with risperidone , so that significantly fewer risperidone‐treated patients required antiparkinsonian medication Sixty‐three chronic schizophrenic in‐ patients were included in the double‐blind , double‐dummy clinical trial comparing antipsychotic activity and side effects of cis(Z)‐clopenthixol and haloperidol . Test treatment was administered at least 8 and in most cases 12 weeks with clinical evaluations including BPRS , NOSIE‐30 , CGI and single side effects done at weeks 0 , 2 , 4 , 8 , and 12 . The average end‐of‐trial doses were 40 mg cis(Z)‐clopenthixol and 10 mg haloperidol . Statistically significant improvements of total BPRS‐score and Thinking disturbance were registered with both drugs from week 2 onwards . At week 12 when 36 patients were receiving test treatment total BPRS‐score was reduced by 31 % in the cis(Z)‐clopenthixol group and by 17 % in the haloperidol group . At week 4 Thinking disturbance was reduced by 32 % in the cis(Z)‐clopenthixol group and by 16 % in the haloperidol group ‐ these findings constituted the only significant difference between test drugs . Compared to the BPRS‐ results less improvements and no differences between test drugs were registered with NOSIE‐30 and CGI . Any trends towards different frequency and severity of side effects were in the favour of cis(Z)‐clopenthixol BACKGROUND We compared the efficacy of two neuroleptics with different receptor profiles ( zuclopenthixol and haloperidol ) in learning disabled patients with behavioural disturbance . METHOD A double-blind crossover study ( 2 x 8 weeks ; n = 34 ) , interrupted by a two-week single-blind washout period , was employed . Assessment s included the Schedule for H and icaps , Behaviour , and Skills ( SHBS ) and Clinical Global Impression ( CGI ) . RESULTS The SHBS score was significantly reduced for the zuclopenthixol cohort only . End-point analysis between the two drugs also showed an enhanced effect for zuclopenthixol over haloperidol . CGI scores did not reveal significant differences between the two drugs . CONCLUSION Zuclopenthixol may be superior to haloperidol for the treatment of behavioural disturbances in mentally retarded subjects We carried out a 9-day double-blind clinical trial comparing intramuscular zuclopenthixol acetate with liquid oral haloperidol in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation . A parallel-group design was used with stratification by sex . Zuclopenthixol acetate ( 50 to 150 mg ) was given intramuscularly every 3 days , whereas liquid haloperidol ( 10 to 30 mg daily ) was given orally three times a day , with supplementary doses of each medication given under double-blind conditions when needed for agitation . No other sedative drugs , including benzodiazepines , were administered . The mean daily dose was 18.9 mg for haloperidol as compared with a mean dose per 3 days of 117.6 mg for zuclopenthixol . The two treatments were found to be equally efficacious on the Brief Psychiatric Rating Scale and Clinical Global Impression Scale . Both drugs induced similar extrapyramidal side effects . However , more tremors were associated with zuclopenthixol as was a tendency for tardive dyskinesia to be unmasked at the end of the injection interval . Sedation was higher with zuclopenthixol acetate than with haloperidol . Serum creatinine phosphokinase levels were not significantly increased after zuclopenthixol injections . The results of this trial suggest that zuclopenthixol acetate given intramuscularly every second to third day offers an alternative to conventional liquid oral haloperidol in the management of acute schizophrenia The therapeutic effect of the neuroleptic cis(Z)‐clopenthixol has been compared with that of clopenthixol in mainly chronic schizophrenic patients in a double‐blind 8‐week trial . Forty‐nine of the 54 patients in the trial received clopenthixol in the pre‐trial period . Ratings with CGI and a single side effects form were done at weeks 0 , 2 , 4 , 6 , and 8 . The registration of therapeutic effect at week 8 indicated a symptomatological status quo in both groups of patients while there was a tendency of slightly less interference by cis(Z)‐clopenthixol with patient 's functioning than by clopenthixol . The ratio of therapeutically equipotent cis(Z)‐clopenthixol/clopenthixol doses was found to be 1:2 . It is suggested that long‐term treatment with clopenthixol advantageously may be replaced by cis(Z)‐clopenthixol A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors In a double-blind placebo controlled clinical trial in chronic schizophrenic patients , haloperidol and clopenthixol were found to be effective antipsychotic agents , favorably altering behavior as observed by the psychiatrist , the nurse , and ward attendants . In this respect they appeared to compare adequately to the st and ard drug , chlorpromazine . In this experiment , neither the st and ard drug nor the investigational drugs affected psychological test performance . The expected side effects such as extrapyramidal signs and sedation did occur and in some instances required dose reduction for alleviation . One case of possible hepatoxicity in the CX group occurred at the end of the study and was considered of serious import requiring cessation of medication . It was concluded that these chemically unrelated antipsychotics could be used in practice as therapeutic alternatives , the particular choice depending on side effects and possibly symptomatology The evolution of 28 patients displaying acute forms of psychoses ( schizophrenia , mania , exacerbation of psychosis in chronic cases ) was studied under the treatment with Acuphase Acetate continued with Clopixol Depot . In both therapies a tioxantenic neuroleptic is involved for the acute form of the illness ( Acuphase ) and for the maintenance treatment ( Clopixol Depot ) . The assessment of the results was carried out on individual observation files using Global Rating Scale ( G.R.S. ) , B.P.R.S. and para clinical measurement to appreciate the biological tolerance . Favourable effects of treatment were evident in the first 4 days and in six cases even within the first 24 hours . The whole group of patients showed a significant decrease of morbidity evolving from a high severity to a medium and reduced one . The biological tolerance was very good , 6 to 12 months ' care BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials ABSTRACT — Eighty‐three acutely disturbed , psychotic patients were included in an open multicentre study . The aim of the study was to evaluate the clinical effect of zuclopenthixol acetate in Viscoleo ® ( CPT‐A ) . Each patient received from one to four intramuscular injections of CPT‐A during the 6‐day study period . The duration of action after one injection was between 2 and 3 days and doses from 50 mg to 150 mg were sufficient for most patients The clinical effect of cis(Z)‐clopenthixol has been compared with that of clopenthixol , which is a mixture of the pharmacologically month double‐blind trial were included 57 psychotic patients , mainly schizophrenics . Ratings evaluating severity of illness , therapeutic effect , possible interference of side effects with the patient 's functioning , as well as any individual side effects were done at months 0 , 1 , and 2 A double-blind , multi-centre study was carried out in 49 hospitalized patients with an acute psychosis or an exacerbation of a chronic psychosis to compare the wanted and unwanted effects of the neuroleptics , zuclopenthixol and haloperidol . Patients were allocated at r and om to receive treatment with one or other of the trial drugs for 8 weeks or until discharge . Five patients on zuclopenthixol and 6 on haloperidol were excluded from the efficacy analyses because they did not complete a minimum of 4-weeks ' treatment . Dosage was chosen and adjusted to the individual patient 's condition and response . The average daily doses in Week 4 were 33.5 mg and 10.3 mg , respectively . Clinical assessment s , including CGI , BPRS and the UKU side-effect scale , were done at baseline , and after 1 , 2 , 4 , 6 and 8 weeks of treatment or at discharge if the patient was discharged earlier than Week 8 . Both treatments caused a significant reduction in scores with no between-group differences . More patients in the zuclopenthixol group were discharged early indicating slightly more rapid onset of action . Zuclopenthixol caused a significantly greater improvement in ' anxious-depression ' factor score than haloperidol . The most frequent unwanted effects were extrapyramidal symptoms and there were no significant differences between the groups . The extrapyramidal symptoms tended to be transient in the zuclopenthixol group , but not in the haloperidol group . The study confirmed that both zuclopenthixol and haloperidol were effective drugs in the treatment of acute , psychotic patients . There was a trend towards a slightly more rapid onset of effect and a somewhat stronger anxiolytic-antidepressant effect by zuclopenthixol compared to haloperidol |
13,543 | 30,464,514 | The experimental treatments led to increased incidence and risks of GI events compared to the control treatments ( P<0.05 ) .
Diarrhea was the most common GI event .
Additionally , GI NETs led to higher risk of GI events than pancreatic NETs . | The risk of gastrointestinal ( GI ) events induced by nonoperative therapies in patients with neuroendocrine tumors ( NETs ) is unclear .
Nonoperative therapies include somatostatin analogs , molecular targeted agents , cytotoxic chemotherapy , interferon-α , and peptide receptor radionuclide therapy .
We undertook an up-to- date meta- analysis to determine the incidence and relative risks ( RRs ) of GI events in NET patients treated with these therapies . | Purpose Pasireotide ( SOM230 ) , a novel multireceptor lig and somatostatin analog ( SSA ) , binds with high affinity to four of the five somatostatin receptor subtypes ( sst1–3 , 5 ) . This study evaluated the safety , tolerability , pharmacokinetics , and pharmacodynamics profiles of pasireotide long-acting release ( LAR ) formulation in patients with advanced gastroenteropancreatic neuroendocrine tumor ( GEP NET ) refractory to other SSAs . Methods In this r and omized , multicenter , open-label , phase II study , patients with biopsy-proven primary or metastatic GEP NET refractory to available SSAs were r and omly assigned 1:1:1 to receive pasireotide LAR by deep intragluteal injection at a dose of 20 , 40 , or 60 mg once every 28 days for 3 months . Results Forty-two patients received pasireotide LAR . Adverse events were reported by 34 ( 81 % ) patients , with the most frequently reported including diarrhea , fatigue , abdominal pain , and nausea . Mean fasting glucose levels were increased compared with baseline at all points throughout the study . After the third injection of pasireotide LAR , the median trough plasma concentrations on day 84 were 4.82 , 12.0 , and 19.7 ng/mL in the 20- , 40- , and 60-mg treatment groups , respectively . Drug accumulation was limited for each dose based on the increase in trough concentrations after the first to third injections ( accumulation ratios were approximately 1 from all dose levels ) . Conclusions This study demonstrated that a new , once-monthly , intramuscular LAR formulation of pasireotide was well tolerated in patients with advanced GEP NET . Steady state levels of plasma pasireotide were achieved after three injections To evaluate the treatment of advanced islet-cell carcinoma , we r and omly assigned 84 patients to streptozocin alone or streptozocin plus fluorouracil . Each regimen was given in five-day courses . The most frequent toxic effects were nausea and vomiting , mild and reversible renal toxicity , and bone-marrow depression with the combination regimen . The combination had advantages over streptozocin alone in overall rate of response ( 63 vs. 36 per cent ) and in rates of complete response ( 33 vs. 12 per cent ) . There was no evidence of a preferential response among types of functional tumors . Objective responses were generally of long duration ( median , 17 months ) and of substantive clinical benefit . Treatment with the combination also yielded a survival advantage over treatment with streptozocin alone ( medians , 26 and 16 1/2 months ) , but this difference is not statistically significant . In spite of gastrointestinal side effects , streptozocin combined with fluorouracil appears to be a valuable treatment for advanced islet-cell carcinoma Background Several studies have demonstrated the antitumor activity of first-generation somatostatin analogs ( SSAs ) , primarily targeting somatostatin receptor ( sstr ) subtypes 2 and 5 , in neuroendocrine tumors ( NET ) . Pasireotide , a second-generation SSA , targets multiple sstr subtypes . We compared the efficacy and safety of pasireotide plus everolimus to everolimus alone in patients with advanced , well-differentiated , progressive pancreatic NET . Patients and methods Patients were r and omized 1 : 1 to receive a combination of everolimus ( 10 mg/day , orally ) and pasireotide long-acting release ( 60 mg/28 days , intramuscularly ) or everolimus alone ( 10 mg/day , orally ) ; stratified by prior SSA use , and baseline serum chromogranin A and neuron-specific enolase . The primary end point was progression-free survival ( PFS ) . Secondary end points included overall survival , objective response rate , disease control rate , and safety . Biomarker response was evaluated in an exploratory analysis . Results Of 160 patients enrolled , 79 were r and omized to the combination arm and 81 to the everolimus arm . Baseline demographics and disease characteristics were similar between the treatment arms . No significant difference was observed in PFS : 16.8 months in combination arm versus 16.6 months in everolimus arm ( hazard ratio , 0.99 ; 95 % confidence interval , 0.64 - 1.54 ) . Partial responses were observed in 20.3 % versus 6.2 % of patients in combination arm versus everolimus arm ; however , overall disease control rate was similar ( 77.2 % versus 82.7 % , respectively ) . No significant improvement was observed in median overall survival . Adverse events were consistent with the known safety profile of both the drugs ; grade 3 or 4 fasting hyperglycemia was seen in 37 % versus 11 % of patients , respectively . Conclusions The addition of pasireotide to everolimus was not associated with the improvement in PFS compared with everolimus alone in this study . Further studies to delineate mechanisms by which SSAs slow tumor growth in NET are warranted BACKGROUND Effective systemic therapies for patients with advanced , progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce . We aim ed to assess the efficacy and safety of everolimus compared with placebo in this patient population . METHODS In the r and omised , double-blind , placebo-controlled , phase 3 RADIANT-4 trial , adult patients ( aged ≥18 years ) with advanced , progressive , well-differentiated , non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide . Eligible patients were r and omly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo , both with supportive care . Patients were stratified by tumour origin , performance status , and previous somatostatin analogue treatment . Patients , investigators , and the study sponsor were masked to treatment assignment . The primary endpoint was progression-free survival assessed by central radiology review , analysed by intention to treat . Overall survival was a key secondary endpoint . This trial is registered with Clinical Trials.gov , number NCT01524783 . FINDINGS Between April 3 , 2012 , and Aug 23 , 2013 , a total of 302 patients were enrolled , of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo . Median progression-free survival was 11·0 months ( 95 % CI 9·2 - 13·3 ) in the everolimus group and 3·9 months ( 3·6 - 7·4 ) in the placebo group . Everolimus was associated with a 52 % reduction in the estimated risk of progression or death ( hazard ratio [ HR ] 0·48 [ 95 % CI 0·35 - 0·67 ] , p<0·00001 ) . Although not statistically significant , the results of the first pre-planned interim overall survival analysis indicated that everolimus might be associated with a reduction in the risk of death ( HR 0·64 [ 95 % CI 0·40 - 1·05 ] , one-sided p=0·037 , whereas the boundary for statistical significance was 0·0002 ) . Grade 3 or 4 drug-related adverse events were infrequent and included stomatitis ( in 18 [ 9 % ] of 202 patients in the everolimus group vs 0 of 98 in the placebo group ) , diarrhoea ( 15 [ 7 % ] vs 2 [ 2 % ] ) , infections ( 14 [ 7 % ] vs 0 ) , anaemia ( 8 [ 4 % ] vs 1 [ 1 % ] ) , fatigue ( 7 [ 3 % ] vs 1 [ 1 % ] ) , and hyperglycaemia ( 7 [ 3 % ] vs 0 ) . INTERPRETATION Treatment with everolimus was associated with significant improvement in progression-free survival in patients with progressive lung or gastrointestinal neuroendocrine tumours . The safety findings were consistent with the known side-effect profile of everolimus . Everolimus is the first targeted agent to show robust anti-tumour activity with acceptable tolerability across a broad range of neuroendocrine tumours , including those arising from the pancreas , lung , and gastrointestinal tract . FUNDING Novartis Pharmaceuticals Corporation BACKGROUND This was a two-stage , phase II trial of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor BEZ235 in patients with everolimus-resistant pancreatic neuroendocrine tumours ( pNETs ) ( NCT01658436 ) . PATIENTS AND METHODS In stage 1 , 11 patients received 400 mg BEZ235 orally twice daily ( bid ) . Due to tolerability concerns , a further 20 patients received BEZ235 300 mg bid . Stage 2 would be triggered by a 16-week progression-free survival ( PFS ) rate of ≥60 % in stage 1 . RESULTS As of 30 June , 2014 , 29/31 patients had discontinued treatment . Treatment-related grade 3/4 adverse events were reported in eight ( 72.7 % ) patients at 400 mg and eight ( 40.0 % ) patients at 300 mg , including hyperglycaemia , diarrhoea , nausea , and vomiting . The estimated 16-week PFS rate was 51.6 % ( 90 % confidence interval=35.7 - 67.3 % ) . CONCLUSION BEZ235 was poorly tolerated by patients with everolimus-resistant pNETs at 400 and 300 mg bid doses . Although evidence of disease stability was observed , the study did not proceed to stage 2 BACKGROUND The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in pre clinical models and phase 1 and 2 trials . METHODS We conducted a multinational , r and omized , double-blind , placebo-controlled phase 3 trial of sunitinib in patients with advanced , well-differentiated pancreatic neuroendocrine tumors . All patients had Response Evaluation Criteria in Solid Tumors-defined disease progression documented within 12 months before baseline . A total of 171 patients were r and omly assigned ( in a 1:1 ratio ) to receive best supportive care with either sunitinib at a dose of 37.5 mg per day or placebo . The primary end point was progression-free survival ; secondary end points included the objective response rate , overall survival , and safety . RESULTS The study was discontinued early , after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring sunitinib . Median progression-free survival was 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group ( hazard ratio for progression or death , 0.42 ; 95 % confidence interval [ CI ] , 0.26 to 0.66 ; P<0.001 ) . A Cox proportional-hazards analysis of progression-free survival according to baseline characteristics favored sunitinib in all subgroups studied . The objective response rate was 9.3 % in the sunitinib group versus 0 % in the placebo group . At the data cutoff point , 9 deaths were reported in the sunitinib group ( 10 % ) versus 21 deaths in the placebo group ( 25 % ) ( hazard ratio for death , 0.41 ; 95 % CI , 0.19 to 0.89 ; P=0.02 ) . The most frequent adverse events in the sunitinib group were diarrhea , nausea , vomiting , asthenia , and fatigue . CONCLUSIONS Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival , overall survival , and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00428597 . ) Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors ( NET ) compared with placebo in the RADIANT-3 study . Here , we present the final overall survival ( OS ) data and data on the impact of biomarkers on OS from the RADIANT-3 study . Methods Patients with advanced , progressive , low- or intermediate- grade pancreatic NET were r and omly assigned to everolimus 10 mg/day ( n = 207 ) or placebo ( n = 203 ) . Crossover from placebo to open-label everolimus was allowed on disease progression . Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator 's discretion ( extension phase ) . OS analysis was performed using a stratified log-rank test in the intent-to-treat population . The baseline levels of chromogranin A , neuron-specific enolase , and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored . Results Of 410 patients who were enrolled between July 2007 and March 2014 , 225 received open-label everolimus , including 172 patients ( 85 % ) r and omly assigned initially to the placebo arm . Median OS was 44.0 months ( 95 % CI , 35.6 to 51.8 months ) for those r and omly assigned to everolimus and 37.7 months ( 95 % CI , 29.1 to 45.8 months ) for those r and omly assigned to placebo ( hazard ratio , 0.94 ; 95 % CI , 0.73 to 1.20 ; P = .30 ) . Elevated baseline chromogranin A , neuron-specific enolase , placental growth factor , and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS . The most common adverse events included stomatitis , rash , and diarrhea . Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced , progressive pancreatic NET , the longest OS reported in a phase III study for this population . Everolimus was associated with a survival benefit of 6.3 months , although this finding was not statistically significant . Crossover of patients likely confounded the OS results 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 Objective The objective of this analysis was to compare patient-reported outcomes and health-related quality of life ( HRQoL ) in a pivotal phase III trial of sunitinib versus placebo in patients with progressive , well-differentiated pancreatic neuroendocrine tumors ( NCT00428597 ) . Patients and Methods Patients received sunitinib 37.5 mg ( n = 86 ) or placebo ( n = 85 ) on a continuous daily-dosing schedule until disease progression , unacceptable adverse events ( AEs ) , or death . Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Question naire – Core 30 at baseline , Day 1 of every 4-week cycle , and end of treatment or withdrawal . Changes ≥10 points on each scale or item were deemed clinical ly meaningful . Results Sunitinib had anti-tumor effects and improved progression-free survival ( PFS ) compared with placebo . The study was terminated early for this reason and because of more serious AEs and deaths with placebo . Baseline HRQoL scores were well balanced between study arms , and were generally maintained over time in both groups . In the first 10 cycles , there were no significant differences between groups in global HRQoL , cognitive , emotional , physical , role , and social functioning domains , or symptom scales , except for worsening diarrhea with sunitinib ( p < 0.0001 vs. placebo ) . Insomnia also worsened with sunitinib ( p = 0.0372 vs. placebo ) , but the difference was not clinical ly meaningful . Conclusion With the exception of diarrhea ( a recognized side effect ) , sunitinib had no impact on global HRQoL , functional domains , or symptom scales during the progression-free period . Hence , in patients with pancreatic neuroendocrine tumors , sunitinib provided a benefit in PFS without adversely affecting BACKGROUND & AIMS The effect of octreotide plus interferon-alpha versus octreotide monotherapy on the primary study end points of time to treatment failure ( progression , death , stop of study treatment ) and long-term survival was investigated in patients with progressive metastatic neuroendocrine foregut ( mainly pancreatic ) and midgut tumors . METHODS One hundred nine of 125 registered patients were r and omized starting in January 1995 , and 105 patients ( 51 monotherapy , 54 combination treatment ) were finally analyzed in March 2000 . Tumor growth was assessed at 3-month intervals by computed tomography or magnetic resonance imaging . Long-term survival was studied up to April 2004 in all analyzed patients and in 9 patients not r and omized because of stable disease . RESULTS Partial tumor regression occurred in 2.9 % , 1.9 % , and 5.7 % and stabilization of tumor growth in 44.8 % , 27.6 % , and 15.2 % at 3 , 6 , and 12 months , respectively , with no significant differences between both treatment arms . In March 2000 , 9.5 % of patients were in treatment . Time to treatment failure and long-term survival did not differ significantly between the 2 groups , with a median survival of 32 and 54 months for the octreotide and the combination groups , respectively . Survival was longer in patients not r and omized because of stable disease ( median , 68 months ) and in those with low nuclear Ki-67 . A trend toward longer survival was shown for patients with slow spontaneous tumor growth before r and omization . Patients responding to treatment lived longer than unresponsive patients . CONCLUSIONS Combination treatment was not superior to monotherapy concerning progression-free and long-term survival . Patients responding to treatment and those with slow spontaneous tumor growth had a survival advantage BACKGROUND Cytotoxic chemotherapy is widely used for advanced , unresectable pancreatic and other gastrointestinal foregut neuroendocrine tumours ( NETs ) and the most commonly used regimen combines 5-fluorouracil with streptozocin . The NET01 trial was design ed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin . METHODS Patients with advanced , unresectable NETs of pancreatic , gastrointestinal foregut or unknown primary site were r and omised to receive three-weekly capecitabine ( Cap ) 625 mg/m(2 ) twice daily orally , streptozocin ( Strep ) 1.0 g/m(2 ) intravenously on day 1 , with or without cisplatin ( Cis ) 70 mg/m(2 ) intravenously on day 1 . The primary outcome measure was objective response . Secondary outcome measures included progression-free and overall survival , quality of life , toxicity and biochemical response . RESULTS 86 ( 44 CapStrep , 42 CapStrepCis ) patients were r and omised . Best objective response rate was 12 % ( 95 % confidence interval (CI)=2 - 22 % ) with CapStrep and 16 % ( 95 % CI=4 - 27.4 % ) with CapStrepCis . Disease-control rate was 80 % with CapStrep and 74 % with CapStrepCis . The estimated median progression-free and overall survival were 10.2 and 26.7 months for CapStrep and 9.7 and 27.5 months for CapStrepCis . 44 % of CapStrep and 68 % of CapStrepCis patients experienced grade ≥3 adverse events . INTERPRETATION The efficacies of the novel CapStrep±Cis regimens were very similar . CapStrep was better tolerated than CapStrepCis . The trial was registered as EudraCT : 2004 - 005202 - 71 and IS RCT N : 35124268 Peptide receptor radionuclide therapy is an effective treatment option for patients with well-differentiated somatostatin receptor-expressing neuroendocrine tumors . However , published data result mainly from retrospective monocentric studies . We initiated a multi-institutional , prospect i ve , board- review ed registry for patients treated with peptide receptor radionuclide therapy in Germany in 2009 . In five centers , 297 patients were registered . Primary tumors were mainly derived from pancreas ( 117/297 ) and small intestine ( 80/297 ) , whereas 56 were of unknown primary . Most tumors were well differentiated with median Ki67 proliferation rate of 5 % ( range 0.9 - 70 % ) . Peptide receptor radionuclide therapy was performed using mainly yttrium-90 and /or lutetium-177 as radionuclides in 1 - 8 cycles . Mean overall survival was estimated at 213 months with follow-up between 1 and 230 months after initial diagnosis , and 87 months with follow-up between 1 and 92 months after start of peptide receptor radionuclide therapy . Median overall survival was not yet reached . Subgroup analysis demonstrated that best results were obtained in neuroendocrine tumors with proliferation rate below 20 % . Our results indicate that peptide receptor radionuclide therapy is an effective treatment for well- and moderately differentiated neuroendocrine tumors irrespective of previous therapies and should be regarded as one of the primary treatment options for patients with somatostatin receptor-expressing neuroendocrine tumors AIM OF THE STUDY Gastro-intestinal neuroendocrine tumours ( GI-NETs ) are chemotherapy-resistant tumours . Bevacizumab , an inhibitor of vascular endothelial growth factor ( VEGF ) , has shown promising results in several phase II trials of gastro-entero-pancreatic-NETs . We assessed bevacizumab combined with capecitabine , specifically in GI-NET patients . PATIENTS AND METHODS BEvacizumab in The Treament of neuroEndocrine tumoRs ( BETTER ) was a multicentre , open-label , non-r and omised , two-group phase II trial . Here we present the group of patients with progressive , metastatic , well-differentiated GI-NETs . Patients Eastern Cooperative Oncology Group-performance status (ECOG-PS)⩽2 , Ki-67 proliferation rate < 15 % and no prior systemic chemotherapy were treated with bevacizumab ( 7.5 mg/kg/q3w ) and capecitabine ( 1000 mg/m2 twice daily , orally d1 - 14 , resumed on d22 ) for 6 - 24 months . The primary end-point was progression-free survival ( PFS ) ; secondary end-points included overall survival ( OS ) , response rate , safety and quality of life . RESULTS Of the 49 patients included , 53 % were men , median age was 60 years ( 41 - 82 ) , primary tumour site was ileal in 82 % patients and Ki-67 was < 15 % in 48 patients and not available for one patient . After a maximum of 24 month follow-up per patient , the median PFS by investigator assessment was 23.4 months [ 95 % confidence interval ( CI ) : 13.2 ; not reached ] and the overall disease control rate was 88 % ( 18 % partial response , 70 % stable disease ) . The 2-year survival rate was 85 % . Median OS was not reached . The most frequent grade 3 - 4 adverse events were hypertension ( 31 % ) , diarrhoea ( 14 % ) and h and -foot syndrome ( 10 % ) . CONCLUSION The combination of bevacizumab and capecitabine showed clinical activity and a manageable safety profile in the treatment of GI-NETs that warrant confirmation in a r and omised phase III trial Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first‐line somatostatin analogue therapy have limited therapeutic options . This r and omized , controlled trial evaluated the efficacy and safety of lutetium‐177 (177Lu)–Dotatate in patients with advanced , progressive , somatostatin‐receptor – positive midgut neuroendocrine tumors . Methods We r and omly assigned 229 patients who had well‐differentiated , metastatic midgut neuroendocrine tumors to receive either 177Lu‐Dotatate ( 116 patients ) at a dose of 7.4 GBq every 8 weeks ( four intravenous infusions , plus best supportive care including octreotide long‐acting repeatable [ LAR ] administered intramuscularly at a dose of 30 mg ) ( 177Lu‐Dotatate group ) or octreotide LAR alone ( 113 patients ) administered intramuscularly at a dose of 60 mg every 4 weeks ( control group ) . The primary end point was progression‐free survival . Secondary end points included the objective response rate , overall survival , safety , and the side‐effect profile . The final analysis of overall survival will be conducted in the future as specified in the protocol ; a prespecified interim analysis of overall survival was conducted and is reported here . Results At the data ‐cutoff date for the primary analysis , the estimated rate of progression‐free survival at month 20 was 65.2 % ( 95 % confidence interval [ CI ] , 50.0 to 76.8 ) in the 177Lu‐Dotatate group and 10.8 % ( 95 % CI , 3.5 to 23.0 ) in the control group . The response rate was 18 % in the 177Lu‐Dotatate group versus 3 % in the control group ( P<0.001 ) . In the planned interim analysis of overall survival , 14 deaths occurred in the 177Lu‐Dotatate group and 26 in the control group ( P=0.004 ) . Grade 3 or 4 neutropenia , thrombocytopenia , and lymphopenia occurred in 1 % , 2 % , and 9 % , respectively , of patients in the 177Lu‐Dotatate group as compared with no patients in the control group , with no evidence of renal toxic effects during the observed time frame . Conclusions Treatment with 177Lu‐Dotatate result ed in markedly longer progression‐free survival and a significantly higher response rate than high‐dose octreotide LAR among patients with advanced midgut neuroendocrine tumors . Preliminary evidence of an overall survival benefit was seen in an interim analysis ; confirmation will be required in the planned final analysis . Clinical ly significant myelosuppression occurred in less than 10 % of patients in the 177Lu‐Dotatate group . ( Funded by Advanced Accelerator Applications ; NETTER‐1 Clinical Trials.gov number , NCT01578239 ; EudraCT number 2011‐005049‐11 . |
13,544 | 30,673,625 | Conclusions : NMES and exercise‐based interventions may preserve muscle mass and function in patients with critical illness .
There is a lack of consistency seen in the effects of these interventions .
HIGHLIGHTSNMES and exercise‐based interventions may preserve muscle mass and function . | Purpose : In the critically ill , sarcopenia is associated with a variety of adverse outcomes however there is no consensus regarding its management .
This study aim ed to systematic ally review the evidence for interventions for the management and prevention of sarcopenia in critically ill patients . | Introduction Critically ill patients are characterized by increased loss of muscle mass , partially attributed to sepsis and multiple organ failure , as well as immobilization . Recent studies have shown that electrical muscle stimulation ( EMS ) may be an alternative to active exercise in chronic obstructive pulmonary disease ( COPD ) and chronic heart failure ( CHF ) patients with myopathy . The aim of our study was to investigate the EMS effects on muscle mass preservation of critically ill patients with the use of ultrasonography ( US ) . Methods Forty-nine critically ill patients ( age : 59 ± 21 years ) with an APACHE II admission score ≥13 were r and omly assigned after stratification upon admission to receive daily EMS sessions of both lower extremities ( EMS-group ) or to the control group ( control group ) . Muscle mass was evaluated with US , by measuring the cross sectional diameter ( CSD ) of the vastus intermedius and the rectus femoris of the quadriceps muscle . Results Twenty-six patients were finally evaluated . Right rectus femoris and right vastus intermedius CSD decreased in both groups ( EMS group : from 1.42 ± 0.48 to 1.31 ± 0.45 cm , P = 0.001 control group : from 1.59 ± 0.53 to 1.37 ± 0.5 cm , P = 0.002 ; EMS group : from 0.91 ± 0.39 to 0.81 ± 0.38 cm , P = 0.001 control group : from 1.40 ± 0.64 to 1.11 ± 0.56 cm , P = 0.004 , respectively ) . However , the CSD of the right rectus femoris decreased significantly less in the EMS group ( -0.11 ± 0.06 cm , -8 ± 3.9 % ) as compared to the control group ( -0.21 ± 0.10 cm , -13.9 ± 6.4 % ; P < 0.05 ) and the CSD of the right vastus intermedius decreased significantly less in the EMS group ( -0.10 ± 0.05 cm , -12.5 ± 7.4 % ) as compared to the control group ( -0.29 ± 0.28 cm , -21.5 ± 15.3 % ; P < 0.05 ) . Conclusions EMS is well tolerated and seems to preserve the muscle mass of critically ill patients . The potential use of EMS as a preventive and rehabilitation tool in ICU patients with polyneuromyopathy needs to be further investigated . Trial Registration clinical trials.gov : Objectives : To investigate whether a daily exercise session , using a bedside cycle ergometer , is a safe and effective intervention in preventing or attenuating the decrease in functional exercise capacity , functional status , and quadriceps force that is associated with prolonged intensive care unit stay . A prolonged stay in the intensive care unit is associated with muscle dysfunction , which may contribute to an impaired functional status up to 1 yr after hospital discharge . No evidence is available concerning the effectiveness of an early exercise training intervention to prevent these detrimental complications . Design : R and omized controlled trial . Setting : Medical and surgical intensive care unit at University Hospital Gasthuisberg . Patients : Ninety critically ill patients were included as soon as their cardiorespiratory condition allowed bedside cycling exercise ( starting from day 5 ) , given they still had an expected prolonged intensive care unit stay of at least 7 more days . Interventions : Both groups received respiratory physiotherapy and a daily st and ardized passive or active motion session of upper and lower limbs . In addition , the treatment group performed a passive or active exercise training session for 20 mins/day , using a bedside ergometer . Measurements and Main Results : All outcome data are reflective for survivors . Quadriceps force and functional status were assessed at intensive care unit discharge and hospital discharge . Six-minute walking distance was measured at hospital discharge . No adverse events were identified during and immediately after the exercise training . At intensive care unit discharge , quadriceps force and functional status were not different between groups . At hospital discharge , 6-min walking distance , isometric quadriceps force , and the subjective feeling of functional well-being ( as measured with “ Physical Functioning ” item of the Short Form 36 Health Survey question naire ) were significantly higher in the treatment group ( p < .05 ) . Conclusions : Early exercise training in critically ill intensive care unit survivors enhanced recovery of functional exercise capacity , self-perceived functional status , and muscle force at hospital discharge BACKGROUND Skeletal muscle dysfunction and exercise intolerance are common in severe chronic obstructive pulmonary disease ( COPD ) . We assessed the effectiveness of neuromuscular electrical stimulation ( NMES ) as a home-based exercise therapy . METHODS In this double-blind , placebo-controlled trial , undertaken across three UK National Health Service sites , we r and omly assigned ( 1:1 ) adults with COPD , a forced expiratory volume in 1 s ( FEV1 ) less than 50 % predicted , and incapacitating breathlessness ( Medical Research Council dyspnoea scale ≥4 ) to receive active or placebo NMES , daily over a 6-week period . R and omisation was by an independent system using minimisation to balance age , GOLD stage , and quadriceps strength . Participants and outcome assessors were masked to group allocation . The primary endpoint was change in 6-min walk test ( 6MWT ) distance at 6 weeks . Analysis was by intention to treat . The trial was registered as IS RCT N15985261 and is now closed . FINDINGS Between June 29 , 2012 , and July 4 , 2014 , we enrolled 73 participants , of whom 52 participants were r and omly assigned ; 25 to receive active NMES and 27 to placebo NMES . Change in 6MWT distance was greater in the active NMES group ( mean 29·9 [ 95 % CI 8·9 to 51·0 ] ) compared with in the placebo group ( -5·7 [ -19·9 to 8·4 ] ; mean difference at 6 weeks 35·7 m [ 95 % CI 10·5 to 60·9 ] ; p=0·005 ) . Sensitivity analyses for complete-cases and adjustment for baseline values showed similar results . 6 weeks after stopping the intervention the effect waned ( 7·3 m [ 95 % CI -32·5 to 47·0 ] ; p=0·50 ) . The proportion of participants who had adverse events was similar between groups ( five [ 20 % ] in the active NMES group and nine [ 33 % ] in the placebo group ) . Two participants , one from each group , reported persistent erythema , which was considered to be possibly related to NMES and the use of adhesive electrodes . INTERPRETATION NMES improves functional exercise capacity in patients with severe COPD by enhancing quadriceps muscle mass and function . These data support the use of NMES in the management of patients unable to engage with conventional pulmonary rehabilitation . More work is needed to study how to maintain the effect . FUNDING National Institute for Health Research Introduction The purpose of this trial was to investigate the effectiveness of an exercise rehabilitation program commencing during ICU admission and continuing into the outpatient setting compared with usual care on physical function and health-related quality of life in ICU survivors . Methods We conducted a single-center , assessor-blinded , r and omized controlled trial . One hundred and fifty participants were stratified and r and omized to receive usual care or intervention if they were in the ICU for 5 days or more and had no permanent neurological insult . The intervention group received intensive exercises in the ICU and the ward and as out patients . Participants were assessed at recruitment , ICU admission , hospital discharge and at 3- , 6- and 12-month follow-up . Physical function was evaluated using the Six-Minute Walk Test ( 6MWT ) ( primary outcome ) , the Timed Up and Go Test and the Physical Function in ICU Test . Patient-reported outcomes were measured using the Short Form 36 Health Survey , version 2 ( SF-36v2 ) and Assessment of Quality of Life ( AQoL ) Instrument . Data were analyzed using mixed models . Results The a priori enrollment goal was not reached . There were no between-group differences in demographic and hospital data , including acuity and length of acute hospital stay ( LOS ) ( Acute Physiology and Chronic Health Evaluation II score : 21 vs 19 ; hospital LOS : 20 vs 24 days ) . No significant differences were found for the primary outcome of 6MWT or any other outcomes at 12 months after ICU discharge . However , exploratory analyses showed the rate of change over time and mean between-group differences in 6MWT from first assessment were greater in the intervention group . Conclusions Further research examining the trajectory of improvement with rehabilitation is warranted in this population .Trial registration The trial was registered with the Australian New Zeal and Clinical Trials Registry ACTRN12605000776606 Introduction Critical illness polyneuromyopathy ( CIPNM ) is a common complication of critical illness presenting with muscle weakness and is associated with increased duration of mechanical ventilation and weaning period . No preventive tool and no specific treatment have been proposed so far for CIPNM . Electrical muscle stimulation ( EMS ) has been shown to be beneficial in patients with severe chronic heart failure and chronic obstructive pulmonary disease . Aim of our study was to assess the efficacy of EMS in preventing CIPNM in critically ill patients . Methods One hundred and forty consecutive critically ill patients with an APACHE II score ≥ 13 were r and omly assigned after stratification to the EMS group ( n = 68 ) ( age:61 ± 19 years ) ( APACHE II:18 ± 4 , SOFA:9 ± 3 ) or to the control group ( n = 72 ) ( age:58 ± 18 years ) ( APACHE II:18 ± 5 , SOFA:9 ± 3 ) . Patients of the EMS group received daily EMS sessions . CIPNM was diagnosed clinical ly with the medical research council ( MRC ) scale for muscle strength ( maximum score 60 , < 48/60 cut off for diagnosis ) by two unblinded independent investigators . Duration of weaning from mechanical ventilation and intensive care unit ( ICU ) stay were recorded . Results Fifty two patients could be finally evaluated with MRC ; 24 in the EMS group and 28 in the control group . CIPNM was diagnosed in 3 patients in the EMS group as compared to 11 patients in the control group ( OR = 0.22 ; CI : 0.05 to 0.92 , P = 0.04 ) . The MRC score was significantly higher in patients of the EMS group as compared to the control group [ 58 ( 33 to 60 ) vs. 52 ( 2 to 60 ) respectively , median ( range ) , P = 0.04 ) . The weaning period was statistically significantly shorter in patients of the EMS group vs. the control group [ 1 ( 0 to 10 ) days vs. 3 ( 0 to 44 ) days , respectively , median ( range ) , P = 0.003 ] . Conclusions This study suggests that daily EMS sessions prevent the development of CIPNM in critically ill patients and also result in shorter duration of weaning . Further studies should evaluate which patients benefit more from EMS and explore the EMS characteristics most appropriate for preventing CIPNM.Trial Registration Number Clinical Trials.gov OBJECTIVE It is known that patients in the intensive care unit show an enormous loss of muscle mass . Neuromuscular electrical stimulation is effective in enhancing strength and endurance in immobilized patients . The aim of this study was to evaluate the effects of neuromuscular electrical stimulation on muscle layer thickness of knee extensor muscles in intensive care unit patients . DESIGN R and omized , controlled , double-blind , pilot trial . PATIENTS Thirty-three patients , male to female ratio 26:7 , mean age 55 years ( st and ard deviation 15 ) . METHODS After enrolment in the study , intensive care unit patients ( main diagnoses : polytrauma , cardiovascular diseases , transplantation , pneumonia , cancer ) were stratified ( based on the length of their stay in hospital ) into 2 groups : 17 acute patients ( < 7 days ) and 16 long-term patients ( > 14 days ) . Both groups were r and omized to a stimulation group or a sham-stimulation group . Neuromuscular electrical stimulation was applied to knee extensor muscles for a period of 4 weeks ( session time 30 - 60 minutes , 5 days/week ) . Ultrasound measurements were performed before and after the stimulation period to quantify muscle layer thickness of knee extensor muscles . RESULTS Only stimulated long-term patients ( + 4.9 % ) showed a significant ( p = 0.013 ) increase in muscle layer thickness compared with sham-stimulated patients ( -3.2 % ) . CONCLUSION Neuromuscular electrical stimulation appears to be a useful adjunct to revert muscle wasting in intensive care unit long-term patients ; however , larger studies with a larger sample size are needed to confirm these promising , but preliminary , results Background The effects of neuromuscular electrical stimulation ( NMES ) in critically ill patients after cardiothoracic surgery are unknown . The objectives were to investigate whether NMES prevents loss of muscle layer thickness ( MLT ) and strength and to observe the time variation of MLT and strength from preoperative day to hospital discharge . Methods In this r and omized controlled trial , 54 critically ill patients were r and omized into four strata based on the SAPS II score . Patients were blinded to the intervention . In the intervention group , quadriceps muscles were electrically stimulated bilaterally from the first postoperative day until ICU discharge for a maximum of 14 days . In the control group , the electrodes were applied , but no electricity was delivered . The primary outcomes were MLT measured by ultrasonography and muscle strength evaluated with the Medical Research Council ( MRC ) scale . The secondary functional outcomes were average mobility level , FIM score , Timed Up and Go Test and SF-12 health survey . Additional variables of interest were grip strength and the relation between fluid balance and MLT . Linear mixed models were used to assess the effect of NMES on MLT , MRC score and grip strength . Results NMES had no significant effect on MLT . Patients in the NMES group regained muscle strength 4.5 times faster than patients in the control group . During the first three postoperative days , there was a positive correlation between change in MLT and cumulative fluid balance ( r = 0.43 , P = 0.01 ) . At hospital discharge , all patients regained preoperative levels of muscle strength , but not of MLT . Patients did not regain their preoperative levels of average mobility ( P = 0.04 ) and FIM score ( P = 0.02 ) at hospital discharge , independent of group allocation . Conclusions NMES had no effect on MLT , but was associated with a higher rate in regaining muscle strength during the ICU stay . Regression of intramuscular edema during the ICU stay interfered with measurement of changes in MLT . At hospital discharge patients had regained preoperative levels of muscle strength , but still showed residual functional disability and decreased MLT compared to pre-ICU levels in both groups . Trial registration Clinical trials.gov identifier NCT02391103 . Registered on 7 March 2015 Abstract Background : Electrical muscle stimulation ( EMS ) is applied to critically ill patients in order to improve their muscle strength , thereby preventing hypotrophy and promoting functional recovery . Objective : To assess the effects of early EMS on the range of movement of the ankle joint , and on thigh and leg circumference in critically ill patients . Methods : This is a prospect i ve r and omized clinical trial comprising 11 patients undergoing mechanical ventilation . Before and after EMS the thigh and leg circumference in both lower limbs and the goniometry of the tibiotarsal joint were measured . The angle of 90 ° on the goniometer was taken as the st and ard neutral position ( NP ) , with the arm fixed on the lateral malleolus of the ankle joint . Other measurements , namely dorsiflexion and plantar flexion , referred to as mobile arm , were taken from the NP . These recordings were obtained following an active contraction of the patients ’ muscles . Results : Compared with the electrostimulated limb , a difference in dorsiflexion of the control limb was observed ( 96.2 ± 24.9 versus 119.9 ± 14.1 ° ; p = 0.01 ) . A girth of 10 cm of the leg was found in limb reduction when compared to the electrostimulated one ( 24.7 ± 3.1 versus 26.4 ± 4.0 cm ; p = 0.03 ) . Conclusions : EMS used at low current intensity and for a short duration failed to prevent muscle atrophy in critically ill patients . However , we did find a significant improvement in active dorsiflexion of the ankle joint suggesting that it could help to prevent against stance plantar flexion in these patients STUDY OBJECTIVE To compare the effects of active limb mobilization ( ALM ) with or without electrical stimulation ( ES ) on muscle strength , respiratory rate ( RR ) , heart rate , oxygen saturation , and time needed to transfer from bed to chair in two groups of patients with COPD . DESIGN R and omized , controlled study . SETTING Respiratory high-dependency care unit . PATIENTS Twenty-four bed-bound patients with chronic hypercapnic respiratory failure due to COPD who were receiving mechanical ventilation , with marked peripheral muscle hypotonia and atrophy . METHODS Patients were r and omly assigned either to ALM alone or to ALM plus ES ( ALM/ES ) . ES was applied using square-wave alternate , symmetric , and compensated impulses for 30 min bid . The duration of treatment was 28 days for all patients . RESULTS Muscle strength improved significantly in the overall group of patients ( from 1.75 + /- 0.73 to 3.44 + /- 0.65 , p < 0.05 ) . Comparing the change ( end minus beginning ) of the analyzed variables , ALM/ES significantly improved muscle strength ( 2.16 + /- 1.02 vs 1.25 + /- 0.75 , p = 0.02 ) and RR ( - 1.91 + /- 1.72 vs 0.41 + /- 1.88 , p = 0.004 ) , and decreased the number of days needed to transfer from bed to chair ( 10.75 + /- 2.41 days vs 14.33 + /- 2.53 days , p = 0.001 ) . CONCLUSION In bed-bound patients with COPD receiving mechanical ventilation , with marked peripheral muscle hypotonia and atrophy , application of ES in addition to classical ALM significantly improved muscle strength and decreased the number of days needed to transfer from bed to chair Rationale Survivors of sepsis syndromes have poor outcomes for physical and cognitive function . No investigations of early physical rehabilitation in the intensive care unit have specifically targeted patients with sepsis syndromes . Objective To determine whether early physical rehabilitation improves physical function and associated outcomes in patients with sepsis syndromes . Methods Fifty critically ill adults admitted to a general intensive care unit with sepsis syndromes were recruited into a prospect i ve double-blinded r and omised controlled trial investigating early physical rehabilitation . Measurements Primary outcomes of physical function ( acute care index of function ) and self-reported health-related quality of life were recorded at ICU discharge and 6 months post-hospital discharge , respectively . Secondary measures included inflammatory biomarkers ; Interleukin-6 , Interleukin-10 and tumour necrosis factor-α , blood lactate , fat-free muscle mass , exercise capacity , muscle strength and anxiety . Main results A significant increase in patient self-reported physical function ( 81.8 ± 22.2 vs. 60.0 ± 29.4 ) , p = 0.04 ) and physical role ( 61.4 ± 43.8 vs. 17.1 ± 34.4 , p = 0.005 ) for the SF-36 at 6 months was found in the exercise group . Physical function scores were not significantly different between groups . Muscle strength scores were ( 51.9 ± 10.5 vs. 47.3 ± 13.6 , p = 0.24 ) with the st and ard care mean Medical Research Council Muscle Score ( MRC ) < 48/60 . The mean change of Interleukin-10 increased and was significantly higher in the exercise group ( 1.8 pg/ml , 180 % vs. 0.9 pg/ml , 90 % , p = 0.04 ) . There was no significant difference between groups for lactate , Interleukin-6 , tumour necrosis factor-α , muscle strength , exercise capacity , fat-free mass or hospital anxiety . Conclusion Implementation of early physical rehabilitation can improve self-reported physical function and induce systemic anti-inflammatory effects BACKGROUND Sarcopenia is prevalent in older population s with many causes and varying outcomes however information for use in clinical practice is still lacking . AIMS The aim of this report is to identify the clinical determinants and prognostic significance of sarcopenia in a cohort of hospitalized acutely ill older patients . METHODS Four hundred and thirty two r and omly selected patients had their baseline clinical characteristic data assessed within 72 h of admission , at 6 weeks and at 6 months . Nutritional status was assessed from anthropometric and biochemical data . Sarcopenia was diagnosed from low muscle mass and low muscle strength-h and grip using anthropometric measures based on the European Working Group criteria . RESULTS Compared with patients without sarcopenia , those diagnosed with sarcopenia 44 ( 10 % ) were more likely to be older , have more depression symptoms and lower serum albumin concentration . The length of hospital stay ( LOS ) was significantly longer in patients diagnosed with sarcopenia compared with patients without sarcopenia [ mean ( SD ) LOS 13.4 ( 8.8 ) versus 9.4 ( 7 ) days respectively , p = 0.003 ] . The risk of non-elective readmission in the 6 months follow up period was significantly lower in patients without sarcopenia compared with those diagnosed with sarcopenia ( adjusted hazard ratio .53 ( 95 % CI : .32 to .87 , p = 0.013 ) . The death rate was also lower in patients without sarcopenia 38/388 ( 10 % ) , compared with those with sarcopenia 12/44 ( 27 % ) , p-value = .001 . CONCLUSION Older people with sarcopenia have poor clinical outcome following acute illness compared with those without sarcopenia Introduction In-bed cycling with patients with critical illness has been shown to be safe and feasible , and improves physical function outcomes at hospital discharge . The effects of early in-bed cycling on reducing the rate of skeletal muscle atrophy , and associations with physical and cognitive function are unknown . Methods and analysis A single-centre r and omised controlled trial in a mixed medical-surgical intensive care unit ( ICU ) will be conducted . Adult patients ( n=68 ) who are expected to be mechanically ventilated for more than 48 hours and remain in ICU for a further 48 hours from recruitment will be r and omly allocated into either ( 1 ) a usual care group or ( 2 ) a group that receives usual care and additional in-bed cycling sessions . The primary outcome is change in rectus femoris cross-sectional area at day 10 in comparison to baseline measured by blinded assessors . Secondary outcome measures include muscle strength , incidence of ICU-acquired weakness , h and grip strength , time to achieve functional milestones ( sitting out of bed , walking ) , Functional Status Score in ICU , ICU Mobility Scale , 6 min walk test 1 week post-ICU discharge , incidence of delirium and quality of life ( EuroQol Five Dimensions question naire Five Levels scale ) . Quality of life assessment s will be conducted post-ICU admission at day 10 , 3 and 6 months after acute hospital discharge . Participants in the intervention group will complete an acceptability of intervention question naire . Ethics and dissemination Appropriate ethical approval from Metro South Health Human Research Ethics Committee has been attained . Results will be published in peer- review ed publications and presented at scientific conferences to assist planning of future multicentre r and omised controlled trials ( if indicated ) that will test in-bed cycling as an intervention to improve the physical , cognitive and health-related quality of life outcomes of patients with critical illness . Trial registration number This trial has been prospect ively registered on the Australian and New Zeal and Clinical Trial Registry ( ACTRN12616000948493 ) ; Pre- results IMPORTANCE Physical rehabilitation in the intensive care unit ( ICU ) may improve the outcomes of patients with acute respiratory failure . OBJECTIVE To compare st and ardized rehabilitation therapy ( SRT ) to usual ICU care in acute respiratory failure . DESIGN , SETTING , AND PARTICIPANTS Single-center , r and omized clinical trial at Wake Forest Baptist Medical Center , North Carolina . Adult patients ( mean age , 58 years ; women , 55 % ) admitted to the ICU with acute respiratory failure requiring mechanical ventilation were r and omized to SRT ( n=150 ) or usual care ( n=150 ) from October 2009 through May 2014 with 6-month follow-up . INTERVENTIONS Patients in the SRT group received daily therapy until hospital discharge , consisting of passive range of motion , physical therapy , and progressive resistance exercise . The usual care group received weekday physical therapy when ordered by the clinical team . For the SRT group , the median ( interquartile range [ IQR ] ) days of delivery of therapy were 8.0 ( 5.0 - 14.0 ) for passive range of motion , 5.0 ( 3.0 - 8.0 ) for physical therapy , and 3.0 ( 1.0 - 5.0 ) for progressive resistance exercise . The median days of delivery of physical therapy for the usual care group was 1.0 ( IQR , 0.0 - 8.0 ) . MAIN OUTCOMES AND MEASURES Both groups underwent assessor-blinded testing at ICU and hospital discharge and at 2 , 4 , and 6 months . The primary outcome was hospital length of stay ( LOS ) . Secondary outcomes were ventilator days , ICU days , Short Physical Performance Battery ( SPPB ) score , 36-item Short-Form Health Surveys ( SF-36 ) for physical and mental health and physical function scale score , Functional Performance Inventory ( FPI ) score , Mini-Mental State Examination ( MMSE ) score , and h and grip and h and held dynamometer strength . RESULTS Among 300 r and omized patients , the median hospital LOS was 10 days ( IQR , 6 to 17 ) for the SRT group and 10 days ( IQR , 7 to 16 ) for the usual care group ( median difference , 0 [ 95 % CI , -1.5 to 3 ] , P = .41 ) . There was no difference in duration of ventilation or ICU care . There was no effect at 6 months for h and grip ( difference , 2.0 kg [ 95 % CI , -1.3 to 5.4 ] , P = .23 ) and h and held dynamometer strength ( difference , 0.4 lb [ 95 % CI , -2.9 to 3.7 ] , P = .82 ) , SF-36 physical health score ( difference , 3.4 [ 95 % CI , -0.02 to 7.0 ] , P = .05 ) , SF-36 mental health score ( difference , 2.4 [ 95 % CI , -1.2 to 6.0 ] , P = .19 ) , or MMSE score ( difference , 0.6 [ 95 % CI , -0.2 to 1.4 ] , P = .17 ) . There were higher scores at 6 months in the SRT group for the SPPB score ( difference , 1.1 [ 95 % CI , 0.04 to 2.1 , P = .04 ) , SF-36 physical function scale score ( difference , 12.2 [ 95 % CI , 3.8 to 20.7 ] , P = .001 ) , and the FPI score ( difference , 0.2 [ 95 % CI , 0.04 to 0.4 ] , P = .02 ) . CONCLUSIONS AND RELEVANCE Among patients hospitalized with acute respiratory failure , SRT compared with usual care did not decrease hospital LOS . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00976833 Fully se date d patients , being treated in the intensive care unit ( ICU ) , experience substantial skeletal muscle loss . Consequently , survival rate is reduced and full recovery after awakening is compromised . Neuromuscular electrical stimulation ( NMES ) represents an effective method to stimulate muscle protein synthesis and alleviate muscle disuse atrophy in healthy subjects . We investigated the efficacy of twice-daily NMES to alleviate muscle loss in six fully se date d ICU patients admitted for acute critical illness [ n=3 males , n=3 females ; age 63 ± 6 y ; APACHE II ( Acute Physiology and Chronic Health Evaluation II ) disease-severity-score : 29 ± 2 ] . One leg was subjected to twice-daily NMES of the quadriceps muscle for a period of 7 ± 1 day whereas the other leg acted as a non-stimulated control ( CON ) . Directly before the first and on the morning after the final NMES session , quadriceps muscle biopsies were collected from both legs to assess muscle fibre-type-specific cross-sectional area ( CSA ) . Furthermore , phosphorylation status of the key proteins involved in the regulation of muscle protein synthesis was assessed and mRNA expression of selected genes was measured . In the CON leg , type 1 and type 2 muscle-fibre-CSA decreased by 16 ± 9 % and 24 ± 7 % respectively ( P<0.05 ) . No muscle atrophy was observed in the stimulated leg . NMES increased mammalian target of rapamycin ( mTOR ) phosphorylation by 19 ± 5 % when compared with baseline ( P<0.05 ) , with no changes in the CON leg . Furthermore , mRNA expression of key genes involved in muscle protein breakdown either declined [ forkhead box protein O1 ( FOXO1 ) ; P<0.05 ] or remained unchanged [ muscle atrophy F-box ( MAFBx ) and muscle RING-finger protein-1 ( MuRF1 ) ] , with no differences between the legs . In conclusion , NMES represents an effective and feasible interventional strategy to prevent skeletal muscle atrophy in critically ill comatose patients Objective : Intensive care unit admission is associated with muscle wasting and impaired physical function . We investigated the effect of early transcutaneous electrical muscle stimulation on quadriceps muscle volume in patients with septic shock . Design : R and omized interventional study using a single-legged exercise design with the contralateral leg serving as a paired control . Setting : A mixed 18-bed intensive care unit at a tertiary care university hospital . Patients : Eight adult male intensive care unit patients with septic shock included within 72 hrs of diagnosis . Interventions : After r and omization of the quadriceps muscles , transcutaneous electrical muscle stimulation was applied on the intervention side for 7 consecutive days and for 60 mins per day . All patients underwent computed tomographic scans of both thighs immediately before and after the 7-day treatment period . The quadriceps muscle was manually delineated on the computed tomography slices , and muscle volumes were calculated after three-dimensional reconstruction . Measurements and Main Results : Median age and Acute Physiology and Chronic Health Evaluation II score were 67 years ( interquartile range , 64–72 years ) and 25 ( interquartile range , 20–29 ) , respectively . During the 7-day study period , the volume of the quadriceps muscle on the control thigh decreased by 16 % ( 4–21 % , p = .03 ) corresponding to a rate of 2.3 % per day . The volume of the stimulated muscle decreased by 20 % ( 3–25 % , p = .04 ) corresponding to a rate of 2.9 % per day ( p = .12 for the difference in decrease ) . There was no difference in muscle volume between the stimulated and nonstimulated thigh at baseline ( p = .10 ) or at day 7 ( p = .12 ) . The charge delivered to the muscle tissue per training session ( 0.82 [ 0.66–1.18 ] coulomb ) correlated with the maximum sequential organ failure assessment score . Conclusions : We observed a marked decrease in quadriceps volume within the first week of intensive care for septic shock . This loss of muscle mass was unaffected by transcutaneous electrical muscle stimulation applied for 60 mins per day for 7 days Purpose The aim of this study was to investigate feasibility of exercise-based rehabilitation delivered after hospital discharge in patients with intensive care unit – acquired weakness ( ICU-AW ) . Material s and methods Twenty adult patients , mechanically ventilated for more than 48 hours , with ICU-AW diagnosis at ICU discharge were included in a pilot feasibility r and omized controlled trial receiving a 16-session exercise-based rehabilitation program . Twenty-one patients without ICU-AW participated in a nested observational cohort study . Feasibility , clinical , and patient-centered outcomes were measured at hospital discharge and at 3 months . Results Intervention feasibility was demonstrated by high adherence and patient acceptability , and absence of adverse events , but this must be offset by the low proportion of enrolment for those screened . The study was underpowered to detect effectiveness of the intervention . The use of manual muscle testing for the diagnosis of ICU-AW lacked robustness as an eligibility criterion and lacked discrimination for identifying rehabilitation requirements . Process evaluation of the trial identified method ological factors , categorized by “ population , ” “ intervention , ” “ control group , ” and “ outcome . ” Conclusions Important data detailing the design , conduct , and implementation of a multicenter r and omized controlled trial of exercise-based rehabilitation for survivors of critical illness after hospital discharge have been reported . Registration Clinical Trials Identifier OBJECTIVE The authors set out to determine whether immediate enteral feeding minimizes early postoperative decreases in h and grip and respiratory muscle strength . SUMMARY BACKGROUND DATA Muscle strength decreases considerably after major surgical procedures . Enteral feeding has been shown to restore strength rapidly in other clinical setting s. METHODS A r and omized , controlled , nonblinded clinical trial was conducted in patients undergoing esophagectomy or pancreatoduodenectomy who received immediate postoperative enteral feeding via jejunostomy ( fed , n = 13 ) , or no enteral feeding during the first 6 postoperative days ( unfed , n = 15 ) . H and grip strength , vital capacity , forced expiratory volume in one second ( FEV1 ) , and maximal inspiratory pressure ( MIP ) were measured before surgery and on postoperative days 2 , 4 , and 6 . Fatigue and vigor were evaluated before surgery and on postoperative day 6 . Mobility was assessed daily after surgery using a st and ardized descriptive scale . Postoperative urine biochemistry was evaluated in daily 24-hour collection s. RESULTS Postoperative vital capacity ( p < 0.05 ) and FEV1 ( p = 0.07 ) were consistently lower ( 18%-29 % ) in the fed group than in the unfed group , whereas grip strength and maximal inspiratory pressure were not significantly different . Postoperative mobility also was lower in the fed patients ( p < 0.05 ) and tended to recover less rapidly ( p = 0.07 ) . Fatigue increased and vigor decreased after surgery ( both p < or = 0.001 ) , but changes were similar in the fed and unfed groups . Intensive care unit and postoperative hospital stay did not differ between groups . CONCLUSIONS Immediate postoperative jejunal feeding was associated with impaired respiratory mechanics and postoperative mobility and did not influence the loss of muscle strength or the increase in fatigue , which occurred after major surgery . Immediate postoperative enteral feeding should not be routine in well-nourished patients at low risk of nutrition-related complications PURPOSE Patients recovering from critical illness may be left with significant muscle mass loss . This study aim ed to evaluate whether a 6-week program of enhanced physiotherapy and structured exercise ( PEPSE ) and an essential amino acid supplement drink ( glutamine and essential amino acid mixture [ GEAA ] ) improves physical and psychological recovery . MATERIAL S AND METHODS Intensive care patients aged 45 years or older , with a combined intensive care unit stay/pre-intensive care unit stay of 5 days or more were recruited to a r and omized controlled trial examining the effect of PEPSE and GEAA on recovery . The 2 factors were tested in a 2 × 2 factorial design : ( 1 ) GEAA drink twice daily for 3 months and ( 2 ) 6-week PEPSE in first 3 months . Primary efficacy outcome was an improvement in the 6-minute walking test at 3 months . RESULTS A total of 93 patients were r and omized to the study . Patients receiving the PEPSE and GEA had the biggest gains in distance walked in 6-minute walking test ( P < .0001 ) . There were also significant reductions in rates of anxiety in study groups control supplement/PEPSE ( P = .047 ) and GEAA supplement/PEPSE ( P = .036 ) and for GEAA supplement/PEPSE in depression ( P = .0009 ) . CONCLUSION Enhanced rehabilitation combined with GEAA supplement may enhance physical recovery and reduce anxiety and depression IMPORTANCE Systematic review s suggest adult patients in intensive care units ( ICUs ) with relative contraindications to early enteral nutrition ( EN ) may benefit from parenteral nutrition ( PN ) provided within 24 hours of ICU admission . OBJECTIVE To determine whether providing early PN to critically ill adults with relative contraindications to early EN alters outcomes . DESIGN , SETTING , AND PARTICIPANTS Multicenter , r and omized , single-blind clinical trial conducted between October 2006 and June 2011 in ICUs of 31 community and tertiary hospitals in Australia and New Zeal and . Participants were critically ill adults with relative contraindications to early EN who were expected to remain in the ICU longer than 2 days . INTERVENTIONS R and om allocation to pragmatic st and ard care or early PN . MAIN OUTCOMES AND MEASURES Day-60 mortality ; quality of life , infections , and body composition . RESULTS A total of 1372 patients were r and omized ( 686 to st and ard care , 686 to early PN ) . Of 682 patients receiving st and ard care , 199 patients ( 29.2 % ) initially commenced EN , 186 patients ( 27.3 % ) initially commenced PN , and 278 patients ( 40.8 % ) remained unfed . Time to EN or PN in patients receiving st and ard care was 2.8 days ( 95 % CI , 2.3 to 3.4 ) . Patients receiving early PN commenced PN a mean of 44 minutes after enrollment ( 95 % CI , 36 to 55 ) . Day-60 mortality did not differ significantly ( 22.8 % for st and ard care vs 21.5 % for early PN ; risk difference , -1.26 % ; 95 % CI , -6.6 to 4.1 ; P = .60 ) . Early PN patients rated day-60 quality of life ( R AND -36 General Health Status ) statistically , but not clinical ly meaningfully , higher ( 45.5 for st and ard care vs 49.8 for early PN ; mean difference , 4.3 ; 95 % CI , 0.95 to 7.58 ; P = .01 ) . Early PN patients required fewer days of invasive ventilation ( 7.73 vs 7.26 days per 10 patient × ICU days , risk difference , -0.47 ; 95 % CI , -0.82 to -0.11 ; P = .01 ) and , based on Subjective Global Assessment , experienced less muscle wasting ( 0.43 vs 0.27 score increase per week ; mean difference , -0.16 ; 95 % CI , -0.28 to -0.038 ; P = .01 ) and fat loss ( 0.44 vs 0.31 score increase per week ; mean difference , -0.13 ; 95 % CI , -0.25 to -0.01 ; P = .04 ) . CONCLUSIONS AND RELEVANCE The provision of early PN to critically ill adults with relative contraindications to early EN , compared with st and ard care , did not result in a difference in day-60 mortality . The early PN strategy result ed in significantly fewer days of invasive ventilation but not significantly shorter ICU or hospital stays . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN012605000704695 Objectives : To determine if the early goal -directed mobilization intervention could be delivered to patients receiving mechanical ventilation with increased maximal levels of activity compared with st and ard care . Design : A pilot r and omized controlled trial . Setting : Five ICUs in Australia and New Zeal and . Participants : Fifty critically ill adults mechanically ventilated for greater than 24 hours . Intervention : Patients were r and omly assigned to either early goal -directed mobilization ( intervention ) or to st and ard care ( control ) . Early goal -directed mobilization comprised functional rehabilitation treatment conducted at the highest level of activity possible for that patient assessed by the ICU mobility scale while receiving mechanical ventilation . Measurements and Main Results : The ICU mobility scale , strength , ventilation duration , ICU and hospital length of stay , and total inpatient ( acute and rehabilitation ) stay as well as 6-month post-ICU discharge health-related quality of life , activities of daily living , and anxiety and depression were recorded . The mean age was 61 years and 60 % were men . The highest level of activity ( ICU mobility scale ) recorded during the ICU stay between the intervention and control groups was mean ( 95 % CI ) 7.3 ( 6.3–8.3 ) versus 5.9 ( 4.9–6.9 ) , p = 0.05 . The proportion of patients who walked in ICU was almost doubled with early goal -directed mobilization ( intervention n = 19 [ 66 % ] vs control n = 8 [ 38 % ] ; p = 0.05 ) . There was no difference in total inpatient stay ( d ) between the intervention versus control groups ( 20 [ 15–35 ] vs 34 [ 18–43 ] ; p = 0.37 ) . There were no adverse events . Conclusions : Key Practice Points : Delivery of early goal -directed mobilization within a r and omized controlled trial was feasible , safe and result ed in increased duration and level of active exercises Purpose Intensive Care Unit ( ICU ) survivors experience muscle weakness leading to restrictions in functional ability . Neuromuscular electrical stimulation ( NMES ) has been an alternative to exercise in critically ill patients . The aim of our study was to investigate its effects along with individualized rehabilitation on muscle strength of ICU survivors . Material and methods Following ICU discharge , 128 patients ( age : 53 ± 16 years ) were r and omly assigned to daily NMES sessions and individualized rehabilitation ( NMES group ) or to control group . Muscle strength was assessed by the Medical Research Council ( MRC ) score and h and grip at hospital discharge . Secondary outcomes were functional ability and hospital length of stay . Results MRC , h and grip , functional status and hospital length of stay did not differ at hospital discharge between groups ( p > 0.05 ) . & Dgr;MRC% one and two weeks after ICU discharge tended to be higher in NMES group , while it was significant higher in NMES group of patients with ICU‐acquired weakness at two weeks ( p = 0.05 ) . Conclusions NMES and personalized physiotherapy in ICU survivors did not result in greater improvement of muscle strength and functional status at hospital discharge . However , in patients with ICU‐aw NMES may be effective . The potential benefits of rehabilitation strategies should be explored in larger number of patients in future studies . Clinical trial registration : www . Clinical trials.gov : NCT01717833 HighlightsR and omized trial implementing Neuromuscular Electrical Stimulation ( NMES ) and rehabilitation program in ICU survivors . The program was performed from ICU discharge to hospital discharge . Outcome measures included assessment of muscle strength , functional ability and hospital length of stay . MRC , h and grip strength , functional status and length of stay did not differ at hospital . MRC improved significantly in patients with ICU‐acquired weakness after 2 weeks of NMES.Intervention may be beneficial in ICU survivors with ICU‐acquired weakness |
13,545 | 31,156,083 | LIMITATIONS Study drug formulation may have prevented some younger children who were unable to swallow whole or crushed tablets from participating .
This trial has not shown any clinical benefit for EC prednisolone therapy in UK children .
The cost-effectiveness analysis suggested that EC therapy may be cheaper , with the possibility of a small QALY benefit . | BACKGROUND The optimal corticosteroid regimen for treating the presenting episode of steroid-sensitive nephrotic syndrome ( SSNS ) remains uncertain .
Most UK centres use an 8-week regimen , despite previous systematic review s indicating that longer regimens reduce the risk of relapse and frequently relapsing nephrotic syndrome ( FRNS ) .
OBJECTIVES The primary objective was to determine whether or not an extended 16-week course of prednisolone increases the time to first relapse .
The secondary objectives were to compare the relapse rate , FRNS and steroid-dependent nephrotic syndrome ( SDNS ) rates , requirement for alternative immunosuppressive agents and corticosteroid-related adverse events ( AEs ) , including adverse behaviour and costs . | Abstract . To investigate whether age at onset of steroid-sensitive nephrotic syndrome ( SSNS ) is predictive of subsequent relapses , or influences outcome , we retrospectively studied 60 patients who were under 10 years of age at onset and were followed for over 10 years . They were divided into three groups according to age at diagnosis : group 1–3 ( 1.0–3.9 years at onset , n=24 ) , group 4–6 ( 4.0–6.9 years at onset , n=22 ) , and group 7–9 ( 7.0–9.9 years at onset , n=14 ) . In the 51 patients with long-term remission , defined as remaining relapse-free over 3 years , the total number of relapses was significantly more in group 1–3 ( n=18 ) than in group 4–6 ( n=19 ) , and the interval between onset and long-term remission was significantly longer . Group 4–6 and group 7–9 had fewer patients with active disease at 10 years , follow-up than group 1–3 , as assessed by the Kaplan-Meier method . These data suggest that the age at onset of SSNS influences the clinical course ( i.e. , frequency of relapses ) and the time to reach long-term remission . An age of less than 4 years at onset of SSNS is associated with greater likelihood for frequent relapses and a greater time interval to attain long-term remission Abstract We have examined , in a prospect i ve r and omized controlled trial , the effect of 8- and 16-week initial steroid treatment on the course of idiopathic nephrotic syndrome ( INS ) . Patients with a first episode of INS were r and omized to receive st and ard 8-week prednisolone ( 2 mg/kg daily for 4 weeks , then 1.5 mg/kg on alternate days for 4 weeks ) or prolonged 16-week prednisolone treatment ( 2 and 1.5 mg/kg daily each for 4 weeks , then 1.5 and 1 mg/kg on alternate days each for 4 weeks ) . Relapses were treated with prednisolone , 2 mg/kg daily for 2 weeks , then 1.5 mg/kg on alternate days for 4 weeks . Of 45 patients , 23 received st and ard therapy and 22 prolonged therapy . The mean duration of follow-up was 29.2 and 27.3 months in the st and ard and prolonged treatment groups , respectively . The time to first relapse was longer in the prolonged treatment ( mean 222.2 days , median 120.0 days ) than the st and ard group ( mean 134.3 days , median 96.5 days ) . The percentage of patients with no relapse at 6 and 12 months after prednisolone withdrawal was 40.9 % and 27.3 % in the prolonged treatment and 21.7 % and 8.7 % in the st and ard groups , respectively . The inability to show statistically significant differences between the two groups was probably related to the small number of patients studied . Prolonged therapy did not affect the subsequent relapse rates and proportion of patients with frequent relapses and steroid dependence . The mean dose of prednisolone received , for the initial episode and relapses during the next year , was higher and associated with significant steroid toxicity in the prolonged treatment group . Our findings suggest that 16-week prednisolone treatment for the initial episode of INS may delay occurrence of the first relapse , but results in significant side effects . Prolongation of initial therapy may be useful in developing countries where frequent infections often induce early relapses Two regimens of steroid treatment for the initial attack of idiopathic nephrotic syndrome ( NS ) in children were compared in a controlled prospect i ve multicentre study . Long prednisone therapy consisted of 60 mg/m2 per 24 h for 6 weeks , followed by alternate day 40 mg/m2 per 48 h for 6 weeks . The st and ard prednisone therapy was 60 mg/m2 per 24 h for 4 weeks , followed by 40 mg/m2 per 48 h for 4 weeks . A total of 71 children with an initial attack of idiopathic NS were allocated at r and om to the two groups . The cumulative rate of patients with sustained remissions after 2 years was significantly higher after the long course than after the st and ard treatment ( 49 % vs 19%,P=0.0079 ) . The mean relapse rate per patient at intervals of 3 , 6 and 12 months was lower in the long-course prednisone group than in the st and ard prednisone group , and the proportion of children with frequent relapses during any subsequent 6 months period was lower in the long-course group than in the st and ard group ( 29 % vs 57%,P=0.03 ) . Mild side-effects of corticosteroid therapy were observed more frequently after long-course prednisone treatment . It is concluded that long-course prednisone therapy of the initial attack of steroid responsive NS is preferable to the st and ard regimen because it reduces the rate of subsequent relapses without increasing the risk for severe steroidal side-effects Abstract Purpose The Strengths and Difficulties Question naire ( SDQ ) is a behavioural screening tool for children . The SDQ is increasingly used as the primary outcome measure in population health interventions involving children , but it is not preference based ; therefore , its role in allocative economic evaluation is limited . The Child Health Utility 9D ( CHU9D ) is a generic preference-based health-related quality of-life measure . This study investigates the applicability of the SDQ outcome measure for use in economic evaluations and examines its relationship with the CHU9D by testing previously published mapping algorithms . The aim of the paper is to explore the feasibility of using the SDQ within economic evaluations of school-based population health interventions . Methods Data were available from children participating in a cluster r and omised controlled trial of the school-based roots of empathy programme in Northern Irel and . Utility was calculated using the original and alternative CHU9D tariffs along with two SDQ mapping algorithms . t tests were performed for pairwise differences in utility values from the preference-based tariffs and mapping algorithms . Results Mean ( st and ard deviation ) SDQ total difficulties and prosocial scores were 12 ( 3.2 ) and 8.3 ( 2.1 ) . Utility values obtained from the original tariff , alternative tariff , and mapping algorithms using five and three SDQ subscales were 0.84 ( 0.11 ) , 0.80 ( 0.13 ) , 0.84 ( 0.05 ) , and 0.83 ( 0.04 ) , respectively . Each method for calculating utility produced statistically significantly different values except the original tariff and five SDQ subscale algorithm . Conclusion Initial evidence suggests the SDQ and CHU9D are related in some of their measurement properties . The mapping algorithm using five SDQ subscales was found to be optimal in predicting mean child health utility . Future research valuing changes in the SDQ scores would contribute to this research In this multicenter , open-label , r and omized controlled trial , we determined whether 2-month prednisolone therapy for steroid-sensitive nephrotic syndrome was inferior or not to 6-month therapy despite significantly less steroid exposure . The primary end point was time from start of initial treatment to start of frequently relapsing nephrotic syndrome . The pre-specified non-inferiority margin was a hazard ratio of 1.3 with one-sided significance of 5 % . We r and omly assigned 255 children with an initial episode of steroid-sensitive nephrotic syndrome to either 2 - or 6-month treatment of which 246 were eligible for final analysis . The total prednisolone exposure counted both initial and relapse prednisolone treatment administered over 24 months . Median follow-up in months was 36.7 in the 2-month and 38.2 in the 6-month treatment group . Time to frequent relaps was similar in both groups ; however , the median was reached only in the 6-month group ( 799 days ) . The hazard ratio was 0.86 ( 90 % confidence interval , 0.64–1.16 ) and met the non-inferior margin . Time to first relapse was also similar in both groups : median day 242 ( 2-month ) and 243 ( 6-month ) . Frequency and severity of adverse events were similar in both groups . Most adverse events were transient and occurred during initial or relapse therapy . Thus , 2 months of initial prednisolone therapy for steroid-sensitive nephrotic syndrome , despite less prednisolone exposure , is not inferior to 6 months of initial therapy in terms of time to onset of frequently relapsing nephrotic syndrome Objectives To compare the motives and experiences of different ethnic groups participating in a r and omised double blind placebo-controlled trial of montelukast in preschool wheeze , and to assess parents ’ or guardians ’ underst and ing of trial procedures and their implication s , including the collection of genetic material . Design Qualitative interviews with parents or guardians . Setting Interviews occurred in the homes of London children recruited to a national multicentre clinical trial following primary and secondary care attendance with wheeze . Participants 42 parents ( 20 of Bangladeshi origin , 10 white UK , 12 other ethnicities ) of preschool children enrolled in a clinical trial . Results Bangladeshi families were relatively reluctant to participate in the qualitative study , despite strong engagement with the parent study . Anxiety related to wheezing was a common primary motive for trial enrolment . Parents viewed the trial as a route to improved treatment . Verbal delivery of trial information appeared more effective than study literature , especially for Bangladeshi families , with low parental literacy and high levels of trust in medical professionals potential contributors to this effect . All ethnic groups expressed a low underst and ing and /or retention of essential study concepts such as r and omisation and genetic testing . Conclusions Bangladeshi families are particularly motivated to participate in clinical trials despite variable comprehension of study concepts . This motivation is more strongly contingent on strong research er-subject rapport than on the quality of study literature . Trial teams seeking to recruit from South Asian population s should emphasise face-to-face verbal explanation of trial concepts and procedures and consider modified trial literature A total of 184 children aged , 13 months to 11 years , suffering from their first attack of steroid-responsive nephrotic syndrome were included in a r and omized study . They were treated according to three treatment protocol s. All children received 1 - 2 mg of prednisone/kg body weight/day ( up to 80 mg daily ) for 4 weeks , and thereafter 1 mg/kg body weight/48 h for the next 4 weeks . Treatment was discontinued at this point in 44 children ( protocol A ) ; in 68 ( protocol B ) the dose was reduced by 25 % each week , tapering off to 0 at the end of the third month , while in 72 children ( protocol C ) , after the first 2 months of initial treatment the dose was reduced by 25 % each month and tapered off to 0 by the end of the sixth month . All patients completed a 2-year follow-up period after withdrawal of prednisone . Treatment results were expressed as : percentage of children relapse-free within the first 6 months and 2 years after withdrawal of treatment , and average number of relapses per patient per year . The best results were obtained in children who had been treated for 6 months ; 65.3 % of them remained relapse-free within the first 6 months and 50 % over the entire 2-year follow-up period ; the number of relapses per patient per year in this group was 0.49 . The respective values for children treated 2 and 3 months were : 36.4 % and 32.4 % for the 6-month period ; 27.3 % and 20.6 % for the 2-year period ; the numbers of relapses per patient per year were 0.79 and 0.77 , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS Ninety six patients aged from 6 months to 15 years and were admitted to Chilean hospitals with the diagnosis of primary nephrotic syndrome in a period of 30 months . These patients were r and omly separated in two groups , group A received prednisone for 8 weeks and group B received the same drug during 12 weeks . All patients were evaluated at 6 , 12 and 18 months after the end of treatment . The moment and number of relapses per patient , accumulated percentage of relapses , relapse rate per 100 patients , total number of relapses and complications were assessed . Frequent relapsers were subjected to a kidney biopsy , leaving in the protocol only those patients that had minimal changes . Patients resistant or dependent to steroid therapy were discarded . Thus we report the results of 56 treated patients followed during 18 months . No differences in analyzed parameters were observed between the two treatment groups . It is concluded that these preliminary results do not support the prolongation of prednisone treatment in children with primary nephrotic syndrome One hundred and fourteen children with primary nephrotic syndrome were followed up prospect ively for periods of between 5 and 14 years . Urine sample s from 94 of them became protein-free during the initial 8-week course of prednisone , and the outcome for these children was good : 74 of them have been free of symptoms for at least 3 years , 18 have had relapses during the last 3 years , and only one child still has proteinuria . All these children have normal renal function and blood pressure . One child died accidentally . Twenty children did not respond to the initial prednisone treatment . Thirteen of them had remissions later , of whom 2 have had relapses during the last 3 years . Seven were totally resistant to prednisone 4 of whom died in renal failure , the remaining 3 have persistent proteinuria with normal levels of creatinine ; one has high blood pressure too . Remission during the initial treatment indicated a good prognosis , but two-thirds of the initial non-responders also fared well The objective of this study was to measure the frequency and severity of the behavioral effects of high-dose oral steroid therapy in children with nephrotic syndrome . We conducted a prospect i ve assessment of the behavior of 12 children using a st and ardized psychological question naire at the time of diagnosis and again after 4 weeks of steroid therapy . A group of control children was also assessed . There was a significant increase in the total behavior score ( P=0.03 ) and specifically in aggressive and poor attention behavior items in the group of nephrotic children compared with the control group . Four of the children with nephrotic syndrome developed abnormal behavior in the clinical range compared with none of the controls . In conclusion , children with nephrotic syndrome treated with high-dose oral steroids are at risk of developing clinical ly relevant behavioral changes Abstract Purpose Quality of life mapping methods such as “ Transfer to Utility ” can be used to translate scores on disease-specific measures to utility values , when traditional utility measurement methods ( e.g. st and ard gamble , time trade-off , preference-based multi-attribute instruments ) have not been used . The aim of this study was to generate preliminary ordinary least squares ( OLS ) regression-based algorithms to transform scores from the Strengths and Difficulties Question naires ( SDQ ) , a widely used measure of mental health in children and adolescents , to utility values obtained using the preference-based Child Health Utility ( CHU9D ) instrument . Methods Two hundred caregivers of children receiving community mental health services completed the SDQ and CHU9D during a telephone interview . Two OLS regressions were run with the CHU9D utility value as the dependent variable and SDQ subscales as predictors . Result ing algorithms were vali date d by comparing predicted and observed group mean utility values in r and omly selected sub sample s. Results Preliminary validation was obtained for two algorithms , utilising five and three subscales of the SDQ , respectively . Root mean square error values ( .124 ) for both models suggested poor fit at an individual level , but both algorithms performed well in predicting mean group observed utility values . Conclusion This research generated algorithms for translating SDQ scores to utility values and providing research ers with an additional tool for conducting health economic evaluations with child and adolescent mental health data While studies show that prolonged initial prednisone therapy reduces the frequency of relapses in nephrotic syndrome , they lack power and have risk of bias . In order to examine the effect of prolonged therapy on frequency of relapses , we conducted a blinded , 1:1 r and omized , placebo-controlled trial in 5 academic hospitals in India on 181 patients , 1 - 12 years old , with a first episode of steroid-sensitive nephrotic syndrome . Following 12 weeks of st and ard therapy , in r and om order , 92 patients received tapering prednisolone while 89 received matching-placebo on alternate days for the next 12 weeks . On intention-to-treat analyses , primary outcome of number of relapses at 1 year was 1.26 in the 6-month group and 1.54 in the 3-month group ( difference -0.28 ; 95 % confidence interval ( CI ) -0.75 , 0.19 ) . Relative relapse rate for 6- vs. 3-month therapy , adjusted for gender , age , and time to initial remission , was 0.70 ( 95 % CI 0.47 - 1.10 ) . Similar proportions of patients had sustained remission , frequent relapses , and adverse effects due to steroids . Adjusted hazard ratios for first relapse and frequent relapses with prolonged therapy were 0.57 ( 95 % CI , 0.36 - 1.07 ) and 1.01 ( 95 % CI , 0.61 - 1.67 ) , respectively . Thus , extending initial prednisolone treatment from 3 to 6 months does not influence the course of illness in children with nephrotic syndrome . These findings have implication s for guiding the duration of therapy of nephrotic syndrome Previous studies of the Arbeitsgemeinschaft für Pädiatrische Nephrologie in children with steroid-sensitive nephrotic syndrome have shown that the length of initial prednisone therapy has an impact on the subsequent relapse rate . The aim of this r and omized , prospect i ve , multicenter study was to reduce the number of relapses further by increasing the initial immunosuppression : Patients with an initial attack of nephrotic syndrome were r and omly allocated to treatment with 6 wk of 60 mg/m(2 ) per d prednisone followed by 6 wk of 40 mg/m(2 ) per 48 h ( Pred group ) or to the same prednisone treatment plus 8 wk of cyclosporine ( Pred+CsA group ) . The primary end point was first relapse ; follow-up was truncated at 2 yr . In the Pred+CsA group ( n = 49 patients ) , the first relapse occurred later compared with the Pred group ( n = 55 patients ) ( median 22.8 versus 12.5 mo ) . After 6 mo , 10.4 % of patients in the Pred+CsA group experienced a first relapse versus 31.5 % in the Pred group ( P = 0.01 ) ; after 1 yr , 36.5 versus 51 % ( P = 0.15 ) ; and after 2 yr , 51 versus 50 % . The mean relapse rate per patient was 0.12 versus 0.57 after 6 mo ( P = 0.01 ) , 0.63 versus 1.03 after 1 yr ( P = 0.02 ) , and 1.03 versus 2.06 after 2 yr ( not significant ) . The significant benefit for adding CsA was lost after 9 to 12 mo . GFR remained unchanged . The subsequent treatment rate with cyclophosphamide was lower in the CsA group ( five versus 12 patients ) after 2 yr . With the use of logistic regression statistics , children who were younger than 7 yr show a significantly better sustained remission rate with initial CsA treatment for the 2-yr observation time ( P = 0.03 ) . It remains question able , however , whether the intensified initial treatment with CsA could be recommended generally BACKGROUND Long-course prednisolone regimens have been shown to be more effective than short-course regimens in sustaining remission of nephrotic syndrome in children . However , the most beneficial approach among the long-course regimens remains unknown . METHODS Seventy-three children with new-onset nephrotic syndrome were allocated at r and om to the two long-course regimens and followed up for 2 years . Group A was administered prednisolone at a daily dose of 60 mg/m2 for 6 weeks , followed by an alternate-day dose of 40 mg/m2 for 6 weeks ( the long daily regimen ) . Group B was administered the same daily dose for 4 weeks , followed by an alternate-day dose of 60 mg/m2 for 4 weeks , and doses were tapered by 10 mg/m2 every 4 weeks ( the long alternate-day regimen ) . RESULTS Group B had a lower incidence of corticosteroid toxicities than group A during the initial treatment . Kaplan-Meier analysis of the sustained remission rate of the two treatment groups showed a marginally significant difference ( P = 0.069 ) and showed a significant difference when patients were stratified for age of disease onset ( P = 0.048 ) . In a subgroup of younger children ( < 4 years at onset ) , group B had a greater rate of sustained remission ( P < 0.01 ) and fewer children with frequent relapses ( P < 0.05 ) than group A , whereas in older children ( > or = 4 years at onset ) , both groups had similar good sustained remission rates . CONCLUSION These findings collectively indicate that the long alternate-day regimen may be more beneficial , with less corticosteroid toxicities , than the long daily regimen , and children with younger age at disease onset may be susceptible to relapse and especially benefit from the long alternate-day regimen for sustaining remission of the disease The ability to predict the course in children with newly diagnosed minimal change nephrotic syndrome ( MCNS ) may have significant therapeutic implication s. Previous attempts based on data available at disease onset have not been successful . Therefore , it was investigated whether characterization of the initial response to adrenocortical steroids and the course during the early months of disease are predictive of the subsequent outcome . Three hundred-eighty-nine children with MCNS , diagnosed at onset , were treated with st and ard prednisone regimens and monitored for up to 17 yr ( mean , 9.4 yr ) . They were classified , after 8 wk of therapy , as initial responders ( complete remission ) or initial nonresponders ( continued proteinuria ) . Subsequent classifications included nonrelapsers , infrequent relapsers , and frequent relapsers . At 8 yr of follow-up , 80 % of patients were in remission . Three-fourths of initial responders who remained in remission during the first 6-month period after initial therapy ( nonrelapsers ; 40 % of the entire series ) either continued in remission during their entire course or relapsed rarely . In contrast , initial relapsers , both frequent and infrequent , achieved a nonrelapsing course only after an average of 3 yr . Unremitting proteinuria during the initial 8 wk of treatment was followed by progression to ESRD in 21 % . When proteinuria during the initial 8 wk continued through the subsequent 6 months , progression to renal failure occurred for 35 % . Although 95 % of children with MCNS do well , 4 to 5 % die from complications or undergo progression to ESRD . Documentation of the early course aids in identifying those at increased risk for a poor outcome . More aggressive therapy may be indicated for these individuals Forty-six children with steroid-responsive nephrotic syndrome were r and omly allocated to receive two different prednisolone regimens for initial therapy . Twenty-nine children ( group 1 ) received an intermittent regimen ( 60 mg/m2/day for 4 weeks , followed by 40/mg/m2/day on 3 days a week for 4 weeks ) ; 17 children ( group 2 ) had a long-term regimen ( 60 mg/m2/day for 4 weeks , followed by the same dose on alternate days for 4 weeks and the doses tapered by 10 mg/m2 , given on alternate days every 4 weeks for 5 months ) . There was no difference between the two groups in the regimen used to treat relapses , steroid responsiveness , number of patients with relapses , and frequency of toxic reactions to steroids . However , the number of patients with a relapse within 6 months after initial therapy and the number of those with frequent relapses or steroid dependence were significantly higher in group 1 than in group 2 ( P less than 0.05 for both ) . The data indicate that the long-term tapering regimen appears to be both safe and preferable to the intermittent regimen for initial therapy in children with idiopathic nephrotic syndrome Prolonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate , but whether this results from the increased duration of treatment or a higher cumulative dose remains unclear . We conducted a r and omized , double-blind , placebo-controlled trial in 69 hospitals in The Netherl and s. We r and omly assigned 150 children ( 9 months to 17 years ) presenting with nephrotic syndrome to either 3 months of prednisolone followed by 3 months of placebo ( n=74 ) or 6 months of prednisolone ( n=76 ) , and median follow-up was 47 months . Both groups received equal cumulative doses of prednisolone ( approximately 3360 mg/m(2 ) ) . Among the 126 children who started trial medication , relapses occurred in 48 ( 77 % ) of 62 patients who received 3 months of prednisolone and 51 ( 80 % ) of 64 patients who received 6 months of prednisolone . Frequent relapses , according to international criteria , occurred with similar frequency between groups as well ( 45 % versus 50 % ) . In addition , there were no statistically significant differences between groups with respect to the eventual initiation of prednisolone maintenance and /or other immunosuppressive therapy ( 50 % versus 59 % ) , steroid dependence , or adverse effects . In conclusion , in this trial , extending initial prednisolone treatment from 3 to 6 months without increasing cumulative dose did not benefit clinical outcome in children with nephrotic syndrome . Previous findings indicating that prolonged treatment regimens reduce relapses most likely result ed from increased cumulative dose rather than the treatment duration BACKGROUND The application of health-related quality of life ( HRQOL ) as a pediatric population health measure may facilitate risk assessment and re source allocation , the tracking of community health , the identification of health disparities , and the determination of health outcomes from interventions and policy decisions . OBJECTIVE To determine the feasibility , reliability , and validity of the 23-item PedsQL 4.0 ( Pediatric Quality of Life Inventory ) Generic Core Scales as a measure of pediatric population health for children and adolescents . DESIGN Mail survey in February and March 2001 to 20 031 families with children ages 2 - 16 years throughout the State of California encompassing all new enrollees in the State 's Children 's Health Insurance Program ( SCHIP ) for those months and targeted language groups . METHODS The PedsQL 4.0 Generic Core Scales ( Physical , Emotional , Social , School Functioning ) were completed by 10 241 families through a statewide mail survey to evaluate the HRQOL of new enrollees in SCHIP . RESULTS The PedsQL 4.0 evidence d minimal missing responses , achieved excellent reliability for the Total Scale Score ( alpha = .89 child;.92 parent report ) , and distinguished between healthy children and children with chronic health conditions . The PedsQL 4.0 was also related to indicators of health care access , days missed from school , days sick in bed or too ill to play , and days needing care . CONCLUSION The results demonstrate the feasibility , reliability , and validity of the PedsQL 4.0 as a pediatric population health outcome . Measuring pediatric HRQOL may be a way to evaluate the health outcomes of SCHIP Abstract A prospect i ve , double-blind controlled trial of the therapeutic effect of azathioprine in children with the nephrotic syndrome is reported . Observations were made in 197 children with the nephrotic syndrome , including 38 who did not respond to corticosteroid therapy ( " non-responders ") and 49 who did respond but relapsed so frequently that they were considered to be at risk of developing steroid toxicity ( " frequent relapsers ") . No advantage of azathioprine over placebo was demonstrated in non-responders , and no significant advantage was seen in frequent relapsers . It is concluded that , under the conditions described , azathioprine should not be given to children with the nephrotic syndrome . Of special interest is a group of patients whose renal-biopsy revealed focal glomerular lesions . These patients had severe morbidity and constituted a third of the total group of corticosteroid non-responders In trial-based cost-effectiveness analysis baseline mean utility values are invariably imbalanced between treatment arms . A patient 's baseline utility is likely to be highly correlated with their quality -adjusted life-years ( QALYs ) over the follow-up period , not least because it typically contributes to the QALY calculation . Therefore , imbalance in baseline utility needs to be accounted for in the estimation of mean differential QALYs , and failure to control for this imbalance can result in a misleading incremental cost-effectiveness ratio . This paper discusses the approaches that have been used in the cost-effectiveness literature to estimate absolute and differential mean QALYs alongside r and omised trials , and illustrates the implication s of baseline mean utility imbalance for QALY calculation . Using data from a recently conducted trial-based cost-effectiveness study and a micro-simulation exercise , the relative performance of alternative estimators is compared , showing that widely used methods to calculate differential QALYs provide incorrect results in the presence of baseline mean utility imbalance regardless of whether these differences are formally statistically significant . It is demonstrated that multiple regression methods can be usefully applied to generate appropriate estimates of differential mean QALYs and an associated measure of sampling variability , while controlling for differences in baseline mean utility between treatment arms in the trial |
13,546 | 32,203,551 | Bone marrow-derived dendritic cells and bone marrow-derived macrophages responded in vitro to VLPs irrespective of whether the VLP also included T-cell epitopes .
The VLPs were internalized and co-localized in the antigen presenting cell lysosomes .
Upon challenge infection , mice vaccinated with the VLPs+T-cell epitopes showed a significantly reduced worm burden , and mounted Trichuris-specific IgM and IgG2c antibody responses .
The protection of mice by VLPs+T-cell epitopes was characterised by the production of mesenteric lymph node (MLN)-derived Th2 cytokines and goblet cell hyperplasia .
Collectively our data establishes that a combination of in silico genome-based CD4 + T cell epitope prediction , combined with VLP delivery , offers a promising pipeline for the development of an effective , safe and affordable helminth vaccine | Trichuris trichiura is a parasite that infects 500 million people worldwide , leading to colitis , growth retardation and Trichuris dysentery syndrome .
There are no licensed vaccines available to prevent Trichuris infection and current treatments are of limited efficacy .
Trichuris infections are linked to poverty , reducing children 's educational performance and the economic productivity of adults .
We employed a systematic , multi-stage process to identify a c and i date vaccine against trichuriasis based on the incorporation of selected T cell epitopes into virus-like particles .
We conducted a systematic review to identify the most appropriate in silico prediction tools to predict histocompatibility complex class II ( MHC-II ) molecule T-cell epitopes . | ABSTRACT We report the first phase I trial to assess the safety and immunogenicity of a malaria vaccine c and i date , ICC-1132 ( Malarivax ) , composed of a modified hepatitis B virus core protein ( HBc ) containing minimal epitopes of the Plasmodium falciparum circumsporozoite ( CS ) protein . When expressed in Escherichia coli , the recombinant ICC-1132 protein forms virus-like particles that were found to be highly immunogenic in pre clinical studies of mice and monkeys . Twenty healthy adult volunteers received a 20- or a 50-μg dose of alum-adsorbed ICC-1132 administered intramuscularly at 0 , 2 , and 6 months . The majority of volunteers in the group receiving the 50-μg dose developed antibodies to CS repeats as well as to HBc . Malaria-specific T cells that secreted gamma interferon were also detected after a single immunization with ICC-1132-alum . These studies support ICC-1132 as a promising malaria vaccine c and i date for further clinical testing using more-potent adjuvant formulations and confirm the potential of modified HBc virus-like particles as a delivery platform for vaccines against other human pathogens ABSTRACT We report the first phase I trial to assess the safety and immunogenicity of a malaria vaccine c and i date , ICC-1132 ( Malarivax ) , composed of a modified hepatitis B virus core protein ( HBc ) containing minimal epitopes of the Plasmodium falciparum circumsporozoite ( CS ) protein . When expressed in Escherichia coli , the recombinant ICC-1132 protein forms virus-like particles that were found to be highly immunogenic in pre clinical studies of mice and monkeys . Twenty healthy adult volunteers received a 20- or a 50-μg dose of alum-adsorbed ICC-1132 administered intramuscularly at 0 , 2 , and 6 months . The majority of volunteers in the group receiving the 50-μg dose developed antibodies to CS repeats as well as to HBc . Malaria-specific T cells that secreted gamma interferon were also detected after a single immunization with ICC-1132-alum . These studies support ICC-1132 as a promising malaria vaccine c and i date for further clinical testing using more-potent adjuvant formulations and confirm the potential of modified HBc virus-like particles as a delivery platform for vaccines against other human pathogens ABSTRACT Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses . In a previous phase I trial , an alum formulation of ICC-1132 , a malaria vaccine c and i date comprising hepatitis B core ( HBc ) virus-like particle containing Plasmodium falciparum circumsporozoite ( CS ) protein epitopes , was shown to elicit Plasmodium falciparum-specific antibody and cellular responses . The present study was design ed as a single-blind , escalating-dose phase I trial to evaluate the safety and immunogenicity of single intramuscular doses of ICC-1132 formulated in the more potent water-in-oil adjuvant Montanide ISA 720 ( ICC-1132/ISA 720 ) . The vaccine was safe and well tolerated , with transient injection site pain as the most frequent complaint . All vaccinees that received either 20 μg or 50 μg of ICC-1132/ISA 720 developed antiimmunogen and anti-HBc antibodies . The majority of volunteers in these two groups developed sporozoite-specific antibodies , predominantly of opsonizing immunoglobulin G subtypes . Peak titers and persistence of parasite-specific antibody following a single injection of the ISA 720 formulated vaccine were comparable to those obtained following two to three immunizations with alum-adsorbed ICC-1132 . Peripheral blood mononuclear cells of ICC-1132/ISA 720 vaccinees proliferated and released cytokines ( interleukin 2 and gamma interferon ) when stimulated with recombinant P. falciparum CS protein , and CS-specific CD4 + T-cell lines were established from volunteers with high levels of antibodies to the repeat region . The promising results obtained with a single dose of ICC-1132 formulated in Montanide ISA 720 encourage further clinical development of this malaria vaccine c and i date ABSTRACT Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses . In a previous phase I trial , an alum formulation of ICC-1132 , a malaria vaccine c and i date comprising hepatitis B core ( HBc ) virus-like particle containing Plasmodium falciparum circumsporozoite ( CS ) protein epitopes , was shown to elicit Plasmodium falciparum-specific antibody and cellular responses . The present study was design ed as a single-blind , escalating-dose phase I trial to evaluate the safety and immunogenicity of single intramuscular doses of ICC-1132 formulated in the more potent water-in-oil adjuvant Montanide ISA 720 ( ICC-1132/ISA 720 ) . The vaccine was safe and well tolerated , with transient injection site pain as the most frequent complaint . All vaccinees that received either 20 μg or 50 μg of ICC-1132/ISA 720 developed antiimmunogen and anti-HBc antibodies . The majority of volunteers in these two groups developed sporozoite-specific antibodies , predominantly of opsonizing immunoglobulin G subtypes . Peak titers and persistence of parasite-specific antibody following a single injection of the ISA 720 formulated vaccine were comparable to those obtained following two to three immunizations with alum-adsorbed ICC-1132 . Peripheral blood mononuclear cells of ICC-1132/ISA 720 vaccinees proliferated and released cytokines ( interleukin 2 and gamma interferon ) when stimulated with recombinant P. falciparum CS protein , and CS-specific CD4 + T-cell lines were established from volunteers with high levels of antibodies to the repeat region . The promising results obtained with a single dose of ICC-1132 formulated in Montanide ISA 720 encourage further clinical development of this malaria vaccine c and i date This open-labeled phase I study provides the first demonstration of the immunogenicity of a precisely defined synthetic polyoxime malaria vaccine in volunteers of diverse HLA types . The polyoxime , design ated (T1BT*)4-P3C , was constructed by chemoselective ligation , via oxime bonds , of a tetrabranched core with a peptide module containing B cell epitopes and a universal T cell epitope of the Plasmodium falciparum circumsporozoite protein . The triepitope polyoxime malaria vaccine was immunogenic in the absence of any exogenous adjuvant , using instead a core modified with the lipopeptide P3C as an endogenous adjuvant . This totally synthetic vaccine formulation can be characterized by mass spectroscopy , thus enabling the reproducible production of precisely defined vaccines for human use . The majority of the polyoxime-immunized volunteers ( 7/10 ) developed high levels of anti-repeat Abs that reacted with the native circumsporozoite on P. falciparum sporozoites . In addition , these seven volunteers all developed T cells specific for the universal epitope , termed T * , which was originally defined using CD4 + T cells from protected volunteers immunized with irradiated P. falciparum sporozoites . The excellent correlation of T*-specific cellular responses with high anti-repeat Ab titers suggests that the T * epitope functioned as a universal Th cell epitope , as predicted by previous peptide/HLA binding assays and by immunogenicity studies in mice of diverse H-2 haplotypes . The current phase I trial suggests that polyoximes may prove useful for the development of highly immunogenic , multicomponent synthetic vaccines for malaria , as well as for other pathogens This open-labeled phase I study provides the first demonstration of the immunogenicity of a precisely defined synthetic polyoxime malaria vaccine in volunteers of diverse HLA types . The polyoxime , design ated (T1BT*)4-P3C , was constructed by chemoselective ligation , via oxime bonds , of a tetrabranched core with a peptide module containing B cell epitopes and a universal T cell epitope of the Plasmodium falciparum circumsporozoite protein . The triepitope polyoxime malaria vaccine was immunogenic in the absence of any exogenous adjuvant , using instead a core modified with the lipopeptide P3C as an endogenous adjuvant . This totally synthetic vaccine formulation can be characterized by mass spectroscopy , thus enabling the reproducible production of precisely defined vaccines for human use . The majority of the polyoxime-immunized volunteers ( 7/10 ) developed high levels of anti-repeat Abs that reacted with the native circumsporozoite on P. falciparum sporozoites . In addition , these seven volunteers all developed T cells specific for the universal epitope , termed T * , which was originally defined using CD4 + T cells from protected volunteers immunized with irradiated P. falciparum sporozoites . The excellent correlation of T*-specific cellular responses with high anti-repeat Ab titers suggests that the T * epitope functioned as a universal Th cell epitope , as predicted by previous peptide/HLA binding assays and by immunogenicity studies in mice of diverse H-2 haplotypes . The current phase I trial suggests that polyoximes may prove useful for the development of highly immunogenic , multicomponent synthetic vaccines for malaria , as well as for other pathogens The objectives of this non-r and omized , non-blinded , dose-escalating Phase I clinical trial were to assess the safety , reactogenicity and immunogenicity of ICC-1132 formulated with Alhydrogel ( aluminum hydroxide ) in 51 healthy , malaria-naive adults aged 18 to 45 years . ICC-1132 ( Malariavax ) is a recombinant , virus-like particle malaria vaccine comprised of hepatitis core antigen engineered to express the central repeat regions from Plasmodium falciparum circumsporozoite protein containing an immunodominant B [ (NANP)3 ] epitope , an HLA-restricted CD4 ( NANPNVDPNANP ) epitope and a universal T cell epitope ( T * ) ( amino acids 326—345 , NF54 isolate ) . We assessed an Alhydrogel ( aluminum hydroxide)-adjuvanted vaccine formulation at three ICC-1132 dose levels , each injected intramuscularly ( 1.0 mL ) on study days 0 , 56 and 168 . A saline vaccine formulation was found to be unstable after prolonged storage and this formulation was subsequently removed from the study . Thirty-two volunteers were followed for one year . Local and systemic adverse clinical events were measured and immune responses to P. falciparum and hepatitis B virus core antigens were determined utilizing the following assays : IgG and IgM ELISA , indirect immunofluorescence against P. falciparum sporozoites , circumsporozoite precipitin ( CSP ) and transgenic sporozoite neutralization assays . Cellular responses were measured by proliferation and IL-2 assays . Local and systemic reactions were similarly mild and well tolerated between dose cohorts . Depending on the ICC-1132 vaccine concentration , 95 to 100 % of volunteers developed antibody responses to the ICC-1132 immunogen and HBc after two injections ; however , only 29—75 % and 29—63 % of volunteers , respectively , developed malaria-specific responses measured by the malaria repeat synthetic peptide ELISA and IFA ; 2 of 8 volunteers had positive reactions in the CSP assay . Maximal transgenic sporozoite neutralization assay inhibition was 54 % . Forty-seven to seventy-five percent demonstrated T cell proliferation in response to ICC-1132 or to recombinant circumsporozoite protein ( rCS ) NF-54 isolate . This c and i date malaria vaccine was well tolerated , but the vaccine formulation was poorly immunogenic . The vaccine may benefit from a more powerful adjuvant to improve immunogenicity . Trial Registration Clinical Trials.gov The objectives of this non-r and omized , non-blinded , dose-escalating Phase I clinical trial were to assess the safety , reactogenicity and immunogenicity of ICC-1132 formulated with Alhydrogel ( aluminum hydroxide ) in 51 healthy , malaria-naive adults aged 18 to 45 years . ICC-1132 ( Malariavax ) is a recombinant , virus-like particle malaria vaccine comprised of hepatitis core antigen engineered to express the central repeat regions from Plasmodium falciparum circumsporozoite protein containing an immunodominant B [ (NANP)3 ] epitope , an HLA-restricted CD4 ( NANPNVDPNANP ) epitope and a universal T cell epitope ( T * ) ( amino acids 326—345 , NF54 isolate ) . We assessed an Alhydrogel ( aluminum hydroxide)-adjuvanted vaccine formulation at three ICC-1132 dose levels , each injected intramuscularly ( 1.0 mL ) on study days 0 , 56 and 168 . A saline vaccine formulation was found to be unstable after prolonged storage and this formulation was subsequently removed from the study . Thirty-two volunteers were followed for one year . Local and systemic adverse clinical events were measured and immune responses to P. falciparum and hepatitis B virus core antigens were determined utilizing the following assays : IgG and IgM ELISA , indirect immunofluorescence against P. falciparum sporozoites , circumsporozoite precipitin ( CSP ) and transgenic sporozoite neutralization assays . Cellular responses were measured by proliferation and IL-2 assays . Local and systemic reactions were similarly mild and well tolerated between dose cohorts . Depending on the ICC-1132 vaccine concentration , 95 to 100 % of volunteers developed antibody responses to the ICC-1132 immunogen and HBc after two injections ; however , only 29—75 % and 29—63 % of volunteers , respectively , developed malaria-specific responses measured by the malaria repeat synthetic peptide ELISA and IFA ; 2 of 8 volunteers had positive reactions in the CSP assay . Maximal transgenic sporozoite neutralization assay inhibition was 54 % . Forty-seven to seventy-five percent demonstrated T cell proliferation in response to ICC-1132 or to recombinant circumsporozoite protein ( rCS ) NF-54 isolate . This c and i date malaria vaccine was well tolerated , but the vaccine formulation was poorly immunogenic . The vaccine may benefit from a more powerful adjuvant to improve immunogenicity . Trial Registration Clinical Trials.gov BACKGROUND Existing anthelmintic drugs ( eg , albendazole and mebendazole ) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted . We aim ed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened . METHODS In this r and omised controlled trial , we compared three drug combinations and one st and ard drug alone in children aged 6 - 14 years in two schools on Pemba Isl and , Tanzania infected with T trichiura and concomitant intestinal nematodes . We assigned children , via a r and omisation list with block sizes of either four or eight , to orally receive albendazole ( 400 mg ) plus ivermectin ( 200 μg/kg ) ; albendazole ( 400 mg ) plus mebendazole ( 500 mg ) ; albendazole ( 400 mg ) plus oxantel pamoate ( 20 mg/kg ) ; or mebendazole ( 500 mg ) alone . The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means , both analysed by available case . This study is registered with IS RCT N , number IS RCT N80245406 . FINDINGS We r and omly assigned 440 eligible children infected with T trichiura between Sept 2 , and Oct 18 , 2013 , to one of the four treatment groups ( 110 children per group ) . Data for 431 children were included in the analysis for the primary endpoints . Albendazole plus oxantel pamoate ( 74 of 108 children cured [ 68·5 % , 95 % CI 59·6 - 77·4 ] ; egg reduction 99·2 % , 98·7 - 99·6 ) and albendazole plus ivermectin ( 30 of 109 cured [ 27·5 % , 19·0 - 36·0 ] ; egg reduction 94·5 % , 91·7 - 96·3 ) were significantly more effective against T trichiura than mebendazole alone ( nine of 107 cured [ 8·4 % , 3·1 - 13·8 ] ; egg reduction 58·5 % , 45·2 - 70·9 ) . Albendazole plus mebendazole had similar low efficacy ( nine of 107 cured [ 8·4 % , 3·1 - 13·8 ; egg reduction 51·6 % , 35·0 - 65·3 ) to mebendazole alone . About a fifth of the children reported adverse events , which were mainly mild . Abdominal cramps and headache were the most common adverse events after treatment ; abdominal cramps were reported by 13 ( 12·0 % ) children for albendazole plus ivermectin , 10 ( 9·3 % ) for albendazole plus mebendazole , 20 ( 18·2 % ) for albendazole plus oxantel pamoate , and 16 ( 14·5 % ) for mebendazole ; headaches were reported by 5 ( 4·6 % ) children for albendazole plus ivermectin , 6 ( 5·6 % ) for albendazole plus mebendazole , 12 ( 10·9 % ) for albendazole plus oxantel pamoate , and 7 ( 6·4 % ) for mebendazole . INTERPRETATION Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes . FUNDING Medicor Foundation and Swiss National Science Foundation BACKGROUND Existing anthelmintic drugs ( eg , albendazole and mebendazole ) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted . We aim ed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened . METHODS In this r and omised controlled trial , we compared three drug combinations and one st and ard drug alone in children aged 6 - 14 years in two schools on Pemba Isl and , Tanzania infected with T trichiura and concomitant intestinal nematodes . We assigned children , via a r and omisation list with block sizes of either four or eight , to orally receive albendazole ( 400 mg ) plus ivermectin ( 200 μg/kg ) ; albendazole ( 400 mg ) plus mebendazole ( 500 mg ) ; albendazole ( 400 mg ) plus oxantel pamoate ( 20 mg/kg ) ; or mebendazole ( 500 mg ) alone . The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means , both analysed by available case . This study is registered with IS RCT N , number IS RCT N80245406 . FINDINGS We r and omly assigned 440 eligible children infected with T trichiura between Sept 2 , and Oct 18 , 2013 , to one of the four treatment groups ( 110 children per group ) . Data for 431 children were included in the analysis for the primary endpoints . Albendazole plus oxantel pamoate ( 74 of 108 children cured [ 68·5 % , 95 % CI 59·6 - 77·4 ] ; egg reduction 99·2 % , 98·7 - 99·6 ) and albendazole plus ivermectin ( 30 of 109 cured [ 27·5 % , 19·0 - 36·0 ] ; egg reduction 94·5 % , 91·7 - 96·3 ) were significantly more effective against T trichiura than mebendazole alone ( nine of 107 cured [ 8·4 % , 3·1 - 13·8 ] ; egg reduction 58·5 % , 45·2 - 70·9 ) . Albendazole plus mebendazole had similar low efficacy ( nine of 107 cured [ 8·4 % , 3·1 - 13·8 ; egg reduction 51·6 % , 35·0 - 65·3 ) to mebendazole alone . About a fifth of the children reported adverse events , which were mainly mild . Abdominal cramps and headache were the most common adverse events after treatment ; abdominal cramps were reported by 13 ( 12·0 % ) children for albendazole plus ivermectin , 10 ( 9·3 % ) for albendazole plus mebendazole , 20 ( 18·2 % ) for albendazole plus oxantel pamoate , and 16 ( 14·5 % ) for mebendazole ; headaches were reported by 5 ( 4·6 % ) children for albendazole plus ivermectin , 6 ( 5·6 % ) for albendazole plus mebendazole , 12 ( 10·9 % ) for albendazole plus oxantel pamoate , and 7 ( 6·4 % ) for mebendazole . INTERPRETATION Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes . FUNDING Medicor Foundation and Swiss National Science Foundation Abstract Allergy is an overreaction by the immune system to a previously encountered , ordinarily harmless substance —typically proteins— result ing in skin rash , swelling of mucous membranes , sneezing or wheezing , or other abnormal conditions . The use of modified proteins is increasingly widespread : their presence in food , commercial products , such as washing powder , and medical therapeutics and diagnostics , makes predicting and identifying potential allergens a crucial societal issue . The prediction of allergens has been explored widely using bioinformatics , with many tools being developed in the last decade ; many of these are freely available online . Here , we report a set of novel models for allergen prediction utilizing amino acid E-descriptors , auto- and cross-covariance transformation , and several machine learning methods for classification , including logistic regression ( LR ) , decision tree ( DT ) , naïve Bayes ( NB ) , r and om forest ( RF ) , multilayer perceptron ( MLP ) and k nearest neighbours ( kNN ) . The best performing method was kNN with 85.3 % accuracy at 5-fold cross-validation . The result ing model has been implemented in a revised version of the AllerTOP server ( http://www.ddg-pharmfac.net/AllerTOP ) . Abstract Allergy is an overreaction by the immune system to a previously encountered , ordinarily harmless substance —typically proteins— result ing in skin rash , swelling of mucous membranes , sneezing or wheezing , or other abnormal conditions . The use of modified proteins is increasingly widespread : their presence in food , commercial products , such as washing powder , and medical therapeutics and diagnostics , makes predicting and identifying potential allergens a crucial societal issue . The prediction of allergens has been explored widely using bioinformatics , with many tools being developed in the last decade ; many of these are freely available online . Here , we report a set of novel models for allergen prediction utilizing amino acid E-descriptors , auto- and cross-covariance transformation , and several machine learning methods for classification , including logistic regression ( LR ) , decision tree ( DT ) , naïve Bayes ( NB ) , r and om forest ( RF ) , multilayer perceptron ( MLP ) and k nearest neighbours ( kNN ) . The best performing method was kNN with 85.3 % accuracy at 5-fold cross-validation . The result ing model has been implemented in a revised version of the AllerTOP server ( http://www.ddg-pharmfac.net/AllerTOP ) . ABSTRACT We report the first phase I trial to assess the safety and immunogenicity of a malaria vaccine c and i date , ICC-1132 ( Malarivax ) , composed of a modified hepatitis B virus core protein ( HBc ) containing minimal epitopes of the Plasmodium falciparum circumsporozoite ( CS ) protein . When expressed in Escherichia coli , the recombinant ICC-1132 protein forms virus-like particles that were found to be highly immunogenic in pre clinical studies of mice and monkeys . Twenty healthy adult volunteers received a 20- or a 50-μg dose of alum-adsorbed ICC-1132 administered intramuscularly at 0 , 2 , and 6 months . The majority of volunteers in the group receiving the 50-μg dose developed antibodies to CS repeats as well as to HBc . Malaria-specific T cells that secreted gamma interferon were also detected after a single immunization with ICC-1132-alum . These studies support ICC-1132 as a promising malaria vaccine c and i date for further clinical testing using more-potent adjuvant formulations and confirm the potential of modified HBc virus-like particles as a delivery platform for vaccines against other human pathogens ABSTRACT We report the first phase I trial to assess the safety and immunogenicity of a malaria vaccine c and i date , ICC-1132 ( Malarivax ) , composed of a modified hepatitis B virus core protein ( HBc ) containing minimal epitopes of the Plasmodium falciparum circumsporozoite ( CS ) protein . When expressed in Escherichia coli , the recombinant ICC-1132 protein forms virus-like particles that were found to be highly immunogenic in pre clinical studies of mice and monkeys . Twenty healthy adult volunteers received a 20- or a 50-μg dose of alum-adsorbed ICC-1132 administered intramuscularly at 0 , 2 , and 6 months . The majority of volunteers in the group receiving the 50-μg dose developed antibodies to CS repeats as well as to HBc . Malaria-specific T cells that secreted gamma interferon were also detected after a single immunization with ICC-1132-alum . These studies support ICC-1132 as a promising malaria vaccine c and i date for further clinical testing using more-potent adjuvant formulations and confirm the potential of modified HBc virus-like particles as a delivery platform for vaccines against other human pathogens ABSTRACT Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses . In a previous phase I trial , an alum formulation of ICC-1132 , a malaria vaccine c and i date comprising hepatitis B core ( HBc ) virus-like particle containing Plasmodium falciparum circumsporozoite ( CS ) protein epitopes , was shown to elicit Plasmodium falciparum-specific antibody and cellular responses . The present study was design ed as a single-blind , escalating-dose phase I trial to evaluate the safety and immunogenicity of single intramuscular doses of ICC-1132 formulated in the more potent water-in-oil adjuvant Montanide ISA 720 ( ICC-1132/ISA 720 ) . The vaccine was safe and well tolerated , with transient injection site pain as the most frequent complaint . All vaccinees that received either 20 μg or 50 μg of ICC-1132/ISA 720 developed antiimmunogen and anti-HBc antibodies . The majority of volunteers in these two groups developed sporozoite-specific antibodies , predominantly of opsonizing immunoglobulin G subtypes . Peak titers and persistence of parasite-specific antibody following a single injection of the ISA 720 formulated vaccine were comparable to those obtained following two to three immunizations with alum-adsorbed ICC-1132 . Peripheral blood mononuclear cells of ICC-1132/ISA 720 vaccinees proliferated and released cytokines ( interleukin 2 and gamma interferon ) when stimulated with recombinant P. falciparum CS protein , and CS-specific CD4 + T-cell lines were established from volunteers with high levels of antibodies to the repeat region . The promising results obtained with a single dose of ICC-1132 formulated in Montanide ISA 720 encourage further clinical development of this malaria vaccine c and i date ABSTRACT Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses . In a previous phase I trial , an alum formulation of ICC-1132 , a malaria vaccine c and i date comprising hepatitis B core ( HBc ) virus-like particle containing Plasmodium falciparum circumsporozoite ( CS ) protein epitopes , was shown to elicit Plasmodium falciparum-specific antibody and cellular responses . The present study was design ed as a single-blind , escalating-dose phase I trial to evaluate the safety and immunogenicity of single intramuscular doses of ICC-1132 formulated in the more potent water-in-oil adjuvant Montanide ISA 720 ( ICC-1132/ISA 720 ) . The vaccine was safe and well tolerated , with transient injection site pain as the most frequent complaint . All vaccinees that received either 20 μg or 50 μg of ICC-1132/ISA 720 developed antiimmunogen and anti-HBc antibodies . The majority of volunteers in these two groups developed sporozoite-specific antibodies , predominantly of opsonizing immunoglobulin G subtypes . Peak titers and persistence of parasite-specific antibody following a single injection of the ISA 720 formulated vaccine were comparable to those obtained following two to three immunizations with alum-adsorbed ICC-1132 . Peripheral blood mononuclear cells of ICC-1132/ISA 720 vaccinees proliferated and released cytokines ( interleukin 2 and gamma interferon ) when stimulated with recombinant P. falciparum CS protein , and CS-specific CD4 + T-cell lines were established from volunteers with high levels of antibodies to the repeat region . The promising results obtained with a single dose of ICC-1132 formulated in Montanide ISA 720 encourage further clinical development of this malaria vaccine c and i date This open-labeled phase I study provides the first demonstration of the immunogenicity of a precisely defined synthetic polyoxime malaria vaccine in volunteers of diverse HLA types . The polyoxime , design ated (T1BT*)4-P3C , was constructed by chemoselective ligation , via oxime bonds , of a tetrabranched core with a peptide module containing B cell epitopes and a universal T cell epitope of the Plasmodium falciparum circumsporozoite protein . The triepitope polyoxime malaria vaccine was immunogenic in the absence of any exogenous adjuvant , using instead a core modified with the lipopeptide P3C as an endogenous adjuvant . This totally synthetic vaccine formulation can be characterized by mass spectroscopy , thus enabling the reproducible production of precisely defined vaccines for human use . The majority of the polyoxime-immunized volunteers ( 7/10 ) developed high levels of anti-repeat Abs that reacted with the native circumsporozoite on P. falciparum sporozoites . In addition , these seven volunteers all developed T cells specific for the universal epitope , termed T * , which was originally defined using CD4 + T cells from protected volunteers immunized with irradiated P. falciparum sporozoites . The excellent correlation of T*-specific cellular responses with high anti-repeat Ab titers suggests that the T * epitope functioned as a universal Th cell epitope , as predicted by previous peptide/HLA binding assays and by immunogenicity studies in mice of diverse H-2 haplotypes . The current phase I trial suggests that polyoximes may prove useful for the development of highly immunogenic , multicomponent synthetic vaccines for malaria , as well as for other pathogens This open-labeled phase I study provides the first demonstration of the immunogenicity of a precisely defined synthetic polyoxime malaria vaccine in volunteers of diverse HLA types . The polyoxime , design ated (T1BT*)4-P3C , was constructed by chemoselective ligation , via oxime bonds , of a tetrabranched core with a peptide module containing B cell epitopes and a universal T cell epitope of the Plasmodium falciparum circumsporozoite protein . The triepitope polyoxime malaria vaccine was immunogenic in the absence of any exogenous adjuvant , using instead a core modified with the lipopeptide P3C as an endogenous adjuvant . This totally synthetic vaccine formulation can be characterized by mass spectroscopy , thus enabling the reproducible production of precisely defined vaccines for human use . The majority of the polyoxime-immunized volunteers ( 7/10 ) developed high levels of anti-repeat Abs that reacted with the native circumsporozoite on P. falciparum sporozoites . In addition , these seven volunteers all developed T cells specific for the universal epitope , termed T * , which was originally defined using CD4 + T cells from protected volunteers immunized with irradiated P. falciparum sporozoites . The excellent correlation of T*-specific cellular responses with high anti-repeat Ab titers suggests that the T * epitope functioned as a universal Th cell epitope , as predicted by previous peptide/HLA binding assays and by immunogenicity studies in mice of diverse H-2 haplotypes . The current phase I trial suggests that polyoximes may prove useful for the development of highly immunogenic , multicomponent synthetic vaccines for malaria , as well as for other pathogens The objectives of this non-r and omized , non-blinded , dose-escalating Phase I clinical trial were to assess the safety , reactogenicity and immunogenicity of ICC-1132 formulated with Alhydrogel ( aluminum hydroxide ) in 51 healthy , malaria-naive adults aged 18 to 45 years . ICC-1132 ( Malariavax ) is a recombinant , virus-like particle malaria vaccine comprised of hepatitis core antigen engineered to express the central repeat regions from Plasmodium falciparum circumsporozoite protein containing an immunodominant B [ (NANP)3 ] epitope , an HLA-restricted CD4 ( NANPNVDPNANP ) epitope and a universal T cell epitope ( T * ) ( amino acids 326—345 , NF54 isolate ) . We assessed an Alhydrogel ( aluminum hydroxide)-adjuvanted vaccine formulation at three ICC-1132 dose levels , each injected intramuscularly ( 1.0 mL ) on study days 0 , 56 and 168 . A saline vaccine formulation was found to be unstable after prolonged storage and this formulation was subsequently removed from the study . Thirty-two volunteers were followed for one year . Local and systemic adverse clinical events were measured and immune responses to P. falciparum and hepatitis B virus core antigens were determined utilizing the following assays : IgG and IgM ELISA , indirect immunofluorescence against P. falciparum sporozoites , circumsporozoite precipitin ( CSP ) and transgenic sporozoite neutralization assays . Cellular responses were measured by proliferation and IL-2 assays . Local and systemic reactions were similarly mild and well tolerated between dose cohorts . Depending on the ICC-1132 vaccine concentration , 95 to 100 % of volunteers developed antibody responses to the ICC-1132 immunogen and HBc after two injections ; however , only 29—75 % and 29—63 % of volunteers , respectively , developed malaria-specific responses measured by the malaria repeat synthetic peptide ELISA and IFA ; 2 of 8 volunteers had positive reactions in the CSP assay . Maximal transgenic sporozoite neutralization assay inhibition was 54 % . Forty-seven to seventy-five percent demonstrated T cell proliferation in response to ICC-1132 or to recombinant circumsporozoite protein ( rCS ) NF-54 isolate . This c and i date malaria vaccine was well tolerated , but the vaccine formulation was poorly immunogenic . The vaccine may benefit from a more powerful adjuvant to improve immunogenicity . Trial Registration Clinical Trials.gov The objectives of this non-r and omized , non-blinded , dose-escalating Phase I clinical trial were to assess the safety , reactogenicity and immunogenicity of ICC-1132 formulated with Alhydrogel ( aluminum hydroxide ) in 51 healthy , malaria-naive adults aged 18 to 45 years . ICC-1132 ( Malariavax ) is a recombinant , virus-like particle malaria vaccine comprised of hepatitis core antigen engineered to express the central repeat regions from Plasmodium falciparum circumsporozoite protein containing an immunodominant B [ (NANP)3 ] epitope , an HLA-restricted CD4 ( NANPNVDPNANP ) epitope and a universal T cell epitope ( T * ) ( amino acids 326—345 , NF54 isolate ) . We assessed an Alhydrogel ( aluminum hydroxide)-adjuvanted vaccine formulation at three ICC-1132 dose levels , each injected intramuscularly ( 1.0 mL ) on study days 0 , 56 and 168 . A saline vaccine formulation was found to be unstable after prolonged storage and this formulation was subsequently removed from the study . Thirty-two volunteers were followed for one year . Local and systemic adverse clinical events were measured and immune responses to P. falciparum and hepatitis B virus core antigens were determined utilizing the following assays : IgG and IgM ELISA , indirect immunofluorescence against P. falciparum sporozoites , circumsporozoite precipitin ( CSP ) and transgenic sporozoite neutralization assays . Cellular responses were measured by proliferation and IL-2 assays . Local and systemic reactions were similarly mild and well tolerated between dose cohorts . Depending on the ICC-1132 vaccine concentration , 95 to 100 % of volunteers developed antibody responses to the ICC-1132 immunogen and HBc after two injections ; however , only 29—75 % and 29—63 % of volunteers , respectively , developed malaria-specific responses measured by the malaria repeat synthetic peptide ELISA and IFA ; 2 of 8 volunteers had positive reactions in the CSP assay . Maximal transgenic sporozoite neutralization assay inhibition was 54 % . Forty-seven to seventy-five percent demonstrated T cell proliferation in response to ICC-1132 or to recombinant circumsporozoite protein ( rCS ) NF-54 isolate . This c and i date malaria vaccine was well tolerated , but the vaccine formulation was poorly immunogenic . The vaccine may benefit from a more powerful adjuvant to improve immunogenicity . Trial Registration Clinical Trials.gov BACKGROUND Existing anthelmintic drugs ( eg , albendazole and mebendazole ) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted . We aim ed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened . METHODS In this r and omised controlled trial , we compared three drug combinations and one st and ard drug alone in children aged 6 - 14 years in two schools on Pemba Isl and , Tanzania infected with T trichiura and concomitant intestinal nematodes . We assigned children , via a r and omisation list with block sizes of either four or eight , to orally receive albendazole ( 400 mg ) plus ivermectin ( 200 μg/kg ) ; albendazole ( 400 mg ) plus mebendazole ( 500 mg ) ; albendazole ( 400 mg ) plus oxantel pamoate ( 20 mg/kg ) ; or mebendazole ( 500 mg ) alone . The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means , both analysed by available case . This study is registered with IS RCT N , number IS RCT N80245406 . FINDINGS We r and omly assigned 440 eligible children infected with T trichiura between Sept 2 , and Oct 18 , 2013 , to one of the four treatment groups ( 110 children per group ) . Data for 431 children were included in the analysis for the primary endpoints . Albendazole plus oxantel pamoate ( 74 of 108 children cured [ 68·5 % , 95 % CI 59·6 - 77·4 ] ; egg reduction 99·2 % , 98·7 - 99·6 ) and albendazole plus ivermectin ( 30 of 109 cured [ 27·5 % , 19·0 - 36·0 ] ; egg reduction 94·5 % , 91·7 - 96·3 ) were significantly more effective against T trichiura than mebendazole alone ( nine of 107 cured [ 8·4 % , 3·1 - 13·8 ] ; egg reduction 58·5 % , 45·2 - 70·9 ) . Albendazole plus mebendazole had similar low efficacy ( nine of 107 cured [ 8·4 % , 3·1 - 13·8 ; egg reduction 51·6 % , 35·0 - 65·3 ) to mebendazole alone . About a fifth of the children reported adverse events , which were mainly mild . Abdominal cramps and headache were the most common adverse events after treatment ; abdominal cramps were reported by 13 ( 12·0 % ) children for albendazole plus ivermectin , 10 ( 9·3 % ) for albendazole plus mebendazole , 20 ( 18·2 % ) for albendazole plus oxantel pamoate , and 16 ( 14·5 % ) for mebendazole ; headaches were reported by 5 ( 4·6 % ) children for albendazole plus ivermectin , 6 ( 5·6 % ) for albendazole plus mebendazole , 12 ( 10·9 % ) for albendazole plus oxantel pamoate , and 7 ( 6·4 % ) for mebendazole . INTERPRETATION Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes . FUNDING Medicor Foundation and Swiss National Science Foundation BACKGROUND Existing anthelmintic drugs ( eg , albendazole and mebendazole ) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted . We aim ed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened . METHODS In this r and omised controlled trial , we compared three drug combinations and one st and ard drug alone in children aged 6 - 14 years in two schools on Pemba Isl and , Tanzania infected with T trichiura and concomitant intestinal nematodes . We assigned children , via a r and omisation list with block sizes of either four or eight , to orally receive albendazole ( 400 mg ) plus ivermectin ( 200 μg/kg ) ; albendazole ( 400 mg ) plus mebendazole ( 500 mg ) ; albendazole ( 400 mg ) plus oxantel pamoate ( 20 mg/kg ) ; or mebendazole ( 500 mg ) alone . The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means , both analysed by available case . This study is registered with IS RCT N , number IS RCT N80245406 . FINDINGS We r and omly assigned 440 eligible children infected with T trichiura between Sept 2 , and Oct 18 , 2013 , to one of the four treatment groups ( 110 children per group ) . Data for 431 children were included in the analysis for the primary endpoints . Albendazole plus oxantel pamoate ( 74 of 108 children cured [ 68·5 % , 95 % CI 59·6 - 77·4 ] ; egg reduction 99·2 % , 98·7 - 99·6 ) and albendazole plus ivermectin ( 30 of 109 cured [ 27·5 % , 19·0 - 36·0 ] ; egg reduction 94·5 % , 91·7 - 96·3 ) were significantly more effective against T trichiura than mebendazole alone ( nine of 107 cured [ 8·4 % , 3·1 - 13·8 ] ; egg reduction 58·5 % , 45·2 - 70·9 ) . Albendazole plus mebendazole had similar low efficacy ( nine of 107 cured [ 8·4 % , 3·1 - 13·8 ; egg reduction 51·6 % , 35·0 - 65·3 ) to mebendazole alone . About a fifth of the children reported adverse events , which were mainly mild . Abdominal cramps and headache were the most common adverse events after treatment ; abdominal cramps were reported by 13 ( 12·0 % ) children for albendazole plus ivermectin , 10 ( 9·3 % ) for albendazole plus mebendazole , 20 ( 18·2 % ) for albendazole plus oxantel pamoate , and 16 ( 14·5 % ) for mebendazole ; headaches were reported by 5 ( 4·6 % ) children for albendazole plus ivermectin , 6 ( 5·6 % ) for albendazole plus mebendazole , 12 ( 10·9 % ) for albendazole plus oxantel pamoate , and 7 ( 6·4 % ) for mebendazole . INTERPRETATION Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes . FUNDING Medicor Foundation and Swiss National Science Foundation Abstract Allergy is an overreaction by the immune system to a previously encountered , ordinarily harmless substance —typically proteins— result ing in skin rash , swelling of mucous membranes , sneezing or wheezing , or other abnormal conditions . The use of modified proteins is increasingly widespread : their presence in food , commercial products , such as washing powder , and medical therapeutics and diagnostics , makes predicting and identifying potential allergens a crucial societal issue . The prediction of allergens has been explored widely using bioinformatics , with many tools being developed in the last decade ; many of these are freely available online . Here , we report a set of novel models for allergen prediction utilizing amino acid E-descriptors , auto- and cross-covariance transformation , and several machine learning methods for classification , including logistic regression ( LR ) , decision tree ( DT ) , naïve Bayes ( NB ) , r and om forest ( RF ) , multilayer perceptron ( MLP ) and k nearest neighbours ( kNN ) . The best performing method was kNN with 85.3 % accuracy at 5-fold cross-validation . The result ing model has been implemented in a revised version of the AllerTOP server ( http://www.ddg-pharmfac.net/AllerTOP ) . Abstract Allergy is an overreaction by the immune system to a previously encountered , ordinarily harmless substance —typically proteins— result ing in skin rash , swelling of mucous membranes , sneezing or wheezing , or other abnormal conditions . The use of modified proteins is increasingly widespread : their presence in food , commercial products , such as washing powder , and medical therapeutics and diagnostics , makes predicting and identifying potential allergens a crucial societal issue . The prediction of allergens has been explored widely using bioinformatics , with many tools being developed in the last decade ; many of these are freely available online . Here , we report a set of novel models for allergen prediction utilizing amino acid E-descriptors , auto- and cross-covariance transformation , and several machine learning methods for classification , including logistic regression ( LR ) , decision tree ( DT ) , naïve Bayes ( NB ) , r and om forest ( RF ) , multilayer perceptron ( MLP ) and k nearest neighbours ( kNN ) . The best performing method was kNN with 85.3 % accuracy at 5-fold cross-validation . The result ing model has been implemented in a revised version of the AllerTOP server ( http://www.ddg-pharmfac.net/AllerTOP ) . |
13,547 | 32,310,996 | Compared with placebos , perioperative intravenous dextrose administration may decrease postoperative nausea but not vomiting . | BACKGROUND It is reported that postoperative nausea and vomiting , common general anesthesia complications , may be prevented by perioperative intravenous dextrose administration , but with controversial clinical effectiveness .
OBJECTIVE To evaluate perioperative intravenous dextrose for preventing postoperative nausea and vomiting through a systematic review and meta- analysis of r and omized controlled trials with trial sequential analysis . | Purpose To examine the effects of iv compound sodium lactate ( CSL ) with and without caloric supplementation with dextrose on nausea , vomiting and pain following general anesthesia for laparoscopy . Methods We compared iv fluid loading with and without supplementary dextrose for the prevention of postoperative nausea and vomiting ( PONV ) . In a prospect i ve double-blinded controlled trial , 120 ASA I female patients undergoing elective gynecological laparoscopy were r and omized to one of three groups , and received either : ( a ) CSL 1.5 mL·kg−1 per hour fasting duration ; ( b ) CSL , 1.5 mL·kg−1 per hour fasting duration with 0.5 g·kg−1 dextrose added in 50 % formulation ( CSL/dextrose ) ; or ( c ) no iv fluid ( control ) . Results Compared with control the percentage of patients who had no PONV within 24 hr of anesthesia in the CSL and CSL/dextrose groups was 78 % vs 83 % and 71 % , P = 0.81 and P = 0.683 respectively . The numbers needed-to-harm for causing PONV episodes in CSL/dextrose vs CSL or control groups were 5.7 [ 95 % confidence interval ( CI ) , 5.57–5.91 ] and 8.2 ( 95 % Cl , 8.01–8.37 ) respectively . The number needed-to-treat for prevention of PONV episodes in CSL vs control was 19.2 ( 95 % Cl , 19.08–19.37 ) . A greater proportion of patients in the CSL/dextrose group required narcotic analgesia in the postanesthetic care unit compared to those in the control group ( 16/35 vs 7/37 , P = 0.03 ) . The CSL/dextrose group also demonstrated hyperglycemia ( serum glucose 14.0 ± 3.94 vs 5.0 ± 1.01 vs 5.2 ± 0.9 mmol·L−1 , P < 0.0001 ) in the postanesthetic care unit compared to the CSL and control groups . The CSL/dextrose group also reported increased thirst at 24 hr compared to control ( 20/35 vs 11/37 , P = 0.035 ) . Conclusion These findings suggest that : I ) administration of dextrose is associated with nausea , increased opioid requirement and late thirst after elective gynecological laparoscopy ; 2 ) iv fluids did not decrease PONVRésuméObjectifVérifier les effets d’un lactate de sodium composé iv ( LSC ) , avec et sans apport calorique complémentaire avec du dextrose , sur les nausées , les vomissements et la douleur après une anesthésie générale pour laparoscopie . MéthodeNous avons comparé une charge liquidienne avec et sans dextrose supplémentaire comme prévention des nausées et vomissements postopératoires ( NVPO ) . Une étude prospect i ve , contrôlée et à double insu a été réalisée auprès de 120 femmes d’état physique ASA I devant subir une laparoscopie gynécologique réglée . Les patientes , réparties en trois groupes , ont reçu : ( a ) 1,5 mL·kg−1 de LSC par heure de jeûne ; ( b ) 1,5 mL·kg−1 de LSC par heure de jeûne avec 0,5 g·kg−1 de dextrose ajouté dans une préparation à 50 % ( LSC/dextrose ) ou ( c ) aucun soluté (témoin).RésultatsComparé à celui des témoins , le pourcentage de patientes sans NVPO pendant les 24 h qui ont suivi l’anesthésie dans les groupes LSC et LSC/dextrose a été respectivement de 78 % vs 83 % et 71 % , P = 0,81 et P = 0,683 . Le nombre de patientes lésées , nécessaire pour causer des NVPO dans le groupe LSC/dextrose vs les groupes LSC ou témoin a été respectivement de 5,1 [ intervalle de confiance de 95 % ( IC ) , 5,57 - 5,91 ] et 8,2 ( IC de 95 % , 8,01 - 8,37 ) . Le nombre nécessaire à traiter pour prévenir les NVPO dans le groupe LSC vs le groupe témoin a été de 19,2 ( IC de 95 % , 19,08 - 19,37 ) . Plus de patientes du groupe LSC/dextrose ont eu besoin d’analgésique narcotique en salle de réveil , comparées aux patientes témoins ( 16/35 vs 7/37 , P = 0,03 ) . À la salle de réveil , on a aussi trouvé de l’hyperglycémie dans le groupe LSC/dextrose ( glucose sérique de 14,0 ± 3,94 vs 5,0 ± 1,01 vs 5,2 ± 0,9 mmol·L−1 , P < 0,0001 ) , comparé aux groupes LSC et témoin . À 24 h , le groupe LSC/dextrose , comparé aux témoins , a aussi présenté une augmentation de la soif , ( 20/35 vs 11/37 , P = 0,035 ) . Conclusion Ces résultats suggèrent que : I ) l’administration de dextrose est associée aux nausées , à des besoins accrus d’opioïde et une soif tardive à la suite d’une laparoscopie gynécologique ; 2 ) les liquides iv ne diminuent pas les NVPO BACKGROUND : Postoperative nausea and vomiting ( PONV ) may occur despite antiemetic prophylaxis and is associated with unanticipated hospital admission , financial impact , and patient dissatisfaction . Previous studies have shown variable impact of IV dextrose on PONV . We sought to determine the relationship of IV dextrose administered during emergence from anesthesia to PONV . METHODS : This was a prospect i ve , double-blind r and omized placebo-controlled trial . Adult female ASA physical status I and II nondiabetic patients scheduled for outpatient gynecologic , urologic , or breast surgery were r and omly assigned to infusion of 250 mL lactated Ringer ’s solution ( group P ; n = 75 ) or dextrose 5 % in lactated Ringer ’s solution ( group D ; n = 87 ) over 2 hours beginning with surgical closing . Blood glucose was determined using a point-of-care device before transfer to the operating room , in the operating room immediately before study fluid infusion , and in the recovery room after study fluid infusion . No antiemetics were given before arrival in the recovery room . PONV scores were recorded at 0 , 30 , 60 , and 120 minutes and 24 hours after arrival in the recovery room . Medication administration was recorded . RESULTS : Data from 162 patients with normal baseline blood glucose were analyzed . There were no significant intergroup differences in demographics , history of PONV , or tobacco use . There was no significant intergroup difference in PONV during the first 2 hours after anesthesia ( group D 52.9 % vs group P 46.7 % ; difference , 6.2 % ; 95 % confidence interval [ CI ] , −9.2 % to 21.6 % ; P = 0.43 ) . Patients in groups D or P who developed PONV within 2 hours of anesthesia had similar number of severity scores ≥1 during recovery stay ( 1.5 vs 1.0 ; difference , 0 ; 95 % CI , 0%–0 % ; P = 0.93 ) ; and similar proportions of : PONV onset within 30 minutes of recovery room arrival ( 65.2 % vs 57.1 % ; difference , 8.1 % ; 95 % CI , −13.1 % to 28.8 % ; P = 0.46 ) ; more than 1 dose of antiemetic medication ( 56.5 % vs 62.9 % ; difference , 6.3 % ; 95 % CI , −26.9 % to 15.1 % ; P= 0.65 ) ; or more than 1 class of antiemetic medication ( 50.0 % vs 54.3 % ; difference , 4.3 % ; 95 % CI , −25.5 % to 17.4 % ; P = 0.82 ) . CONCLUSIONS : The administration of dextrose during emergence from anesthesia was not associated with a difference in the incidence of PONV exceeding 20 % or in the severity of PONV in the first 2 hours after anesthesia . The relationship between PONV and the optimal dose and timing of IV dextrose administration remains unclear and may warrant further study BACKGROUND : Postoperative nausea and vomiting ( PONV ) remains the most common postoperative complication , and causes decreased patient satisfaction , prolonged postoperative hospital stays , and unanticipated admission . There are limited data that indicate that dextrose may reduce nausea and vomiting . In this trial , we attempted to determine whether the rate of PONV can be decreased by postoperative administration of IV dextrose bolus . METHODS : To test the effect of postoperative dextrose administration on PONV rates , we conducted a double-blind , r and omized , placebo-controlled trial . We enrolled 62 nondiabetic , ASA class I or II nonsmoking out patients scheduled for gynecologic laparoscopic and hysteroscopic procedures . Patients were r and omized into 2 groups : the treatment group received dextrose 5 % in Ringer lactate solution , and the control ( placebo ) group received Ringer lactate solution given immediately after surgery . All patients underwent a st and ardized general anesthesia and received 1 dose of antiemetic a half hour before emergence from anesthesia . PONV scores , antiemetic rescue medications , narcotic consumption , and discharge time were recorded in the postanesthesia care unit ( PACU ) in half-hour intervals . RESULTS : The 2 groups were similar with regard to age , weight , anxiety scores , prior PONV , non per os status , presurgical glucose , anesthetic duration , intraoperative narcotic use , and total weight-based fluid volume received . Postoperative nausea scores were not significantly different in the dextrose group compared with the control group ( P > 0.05 ) after Bonferroni correction for repeated measurements over time . However , patients who received dextrose 5 % in Ringer lactate solution consumed less rescue antiemetic medications ( ratio mean difference , 0.56 ; 95 % confidence interval , 0.39–0.82 ; P = 0.02 ) , and had a shorter length of stay in the PACU ( ratio mean difference , 0.80 ; 95 % confidence interval , 0.66–0.97 ; P = 0.03 ) compared with patients in the control group . CONCLUSION : In this trial , postanesthesia IV dextrose administration result ed in improved PONV management as defined by reductions in antiemetic rescue medication requirements and PACU length of stay that are worthy of further study . In light of its ease , low risk , and benefit to patient care and satisfaction , this therapeutic modality could be considered Background and Aims : Post-operative nausea and vomiting ( PONV ) is a common and distressing complication after laparoscopic cholecystectomy ( LC ) . The aim of this study was to evaluate the effect of intravenous ( IV ) dextrose administration for the prophylaxis of PONV after LC . Methods : In a double-blind , r and omised controlled trial , a total of 150 female patients who were scheduled for elective LC were r and omly assigned into two groups ( A and B ) . Thirty minutes before induction of anaesthesia , patients received an infusion of 500 cc lactated Ringer 's solution ( Group A ) and 5 % dextrose in lactated Ringer 's solution ( Group B ) and over a period of 30 min . All patients rated their nausea and vomiting intensity using the verbal rating scale immediately at post-anaesthesia care unit ( PACU ) arrival ; 30 , 60 , 90 and 120 min after arriving at the PACU and 6 , 12 and 24 h after surgery . Results : There was a statistically significant time trend and group effect along with significant differences in time/group interaction effect in both groups for nausea and vomiting scores ( P < 0.05 ) . A low negative correlation coefficient was found ( r = −0.394 , P < 0.001 ) between blood glucose levels and nausea scores upon PACU arrival . Dextrose administration reduced the odds of vomiting events compared to placebo ( estimate : −0.87 , odds ratio = 0.42 , 95 % confidence interval : 0.28–0.64 ) . Conclusion : Administration of IV dextrose before anaesthesia induction may be recommended as an effective , and safe method for the prophylaxis of PONV after LC The potential for preoperative IV rehydration to reduce postoperative nausea and vomiting ( PONV ) and pain in patients undergoing ambulatory surgery remains unclear , with conflicting results reported . We sought to determine whether preoperative IV rehydration with a balanced salt solution would decrease the incidence of PONV in patients at increased risk for these symptoms . Eighty ASA grade I – III patients presenting for gynecologic laparoscopy were r and omized to receive large ( 2 mL/kg per hour fasting ) or small ( 3 mL/kg ) volume infusions of compound sodium lactate solution over 20 min preoperatively . A st and ardized balanced anesthetic was used . The incidence and severity of PONV and pain , and need for supplemental antiemetic and analgesic therapy , were assessed by a blinded investigator at 0.5 , 1 , and 4 h postoperatively , and on the first and third postoperative days . The incidence ( control 87 % versus large volume 59 % ) and severity of PONV were significantly reduced in the large volume infusion group at all time intervals . The large volume infusion group also had decreased postoperative pain scores and required less supplemental analgesia . Preoperative correction of intravascular volume deficits effectively reduces PONV and postoperative pain in high risk patients presenting for ambulatory surgery . We recommend the preoperative administration of 2 mL/kg of compound sodium lactate for every hour of fasting to patients with an increased PONV risk presenting for ambulatory surgery The effect of intra‐operative fluid and dextrose administration upon recovery was tested in a r and omised , double‐blind trial . Three groups of 25 patients , each undergoing laparoscopic examination as day cases , were studied . The two groups who received fluid ( 20 ml/kg compound sodium lactate solution ) showed significant improvement ( p < 0.05 ) in the variables that reflected hydration . The fluid group who also received dextrose ( 1 g/kg ) exhibited further significant improvement . Intra‐operative fluid and dextrose administration appears to confer some benefit upon recovery in patients who have minor surgery BACKGROUND Recent studies have pointed to the role of plasma glucose in the regulation of gastrointestinal function . METHODS We have investigated the effect of acute hyperglycaemia on gastric acid secretion and pancreatic polypeptide ( PP ) release . Gastric acid output was measured under basal conditions and in response to intravenous infusion of gastrin-17 in two doses : 5 pmol kg-1 h for 60 min and 15 pmol kg-1 h for another 60 min . Seven healthy subjects were studied during normoglycaemia and during acute hyperglycaemia at 15 mmol L-1 . Acid output was measured by continuous aspiration using phenol red as recovery marker . Plasma PP levels were determined at regular intervals . RESULTS Gastrin infusion at 5 pmol kg-1 h significantly ( P < 0.05 ) increased acid output both during normoglycaemia and during hyperglycaemia . Gastrin infusion at 15 pmol kg-1 h further and significantly ( P < 0.05 ) increased the acid output during both experiments . Hyperglycaemia significantly ( P < 0 . 05 ) reduced basal acid output ( 2.5 + /- 0.9 vs. 6.3 + /- 1.9 mmol h-1 ) , low-dose gastrin stimulated acid output ( 6.5 + /- 1.7 vs. 13.0 + /- 1 . 8 mmol h-1 ) and high-dose gastrin stimulated acid output ( 11.7 + /- 3 . 0 vs. 19.4 + /- 3.0 mmol h-1 ) compared with normoglycaemia . Plasma PP levels were not stimulated by gastrin-17 infusion and were significantly ( P < 0.05 ) reduced during hyperglycaemia . CONCLUSIONS ( a ) Basal and gastrin-17-stimulated gastric acid secretion are reduced during hyperglycaemia ; ( b ) infusion of gastrin-17 to physiological post-pr and ial levels does not affect plasma PP levels ; ( c ) plasma PP levels are reduced during hyperglycaemia , suggesting vagal-cholinergic inhibition of gastric acid secretion during hyperglycaemia STUDY OBJECTIVE To compare the incidence of postoperative nausea and vomiting ( PONV ) during perioperative administration of 5 % dextrose and normal saline in laparoscopic cholecystectomy . DESIGN Prospect i ve , r and omized , double-blind trial . SETTING Operating rooms in a tertiary care hospital of Northern India . PATIENTS One hundred patients with American Society of Anesthesiologists status I to II undergoing laparoscopic cholecystectomy were enrolled in this study . INTERVENTIONS Patients were r and omized into two groups [ normal saline ( NS ) group and 5 % dextrose ( D ) group ] . Both the groups received Ringer acetate ( Sterofundin ISO ) intravenously as a maintenance fluid during intraoperative period . Besides this , patients of group NS received 250ml of 0.9 % normal saline and patients of group D received 5 % dextrose @ 100ml/h started at the time when gall bladder was taken out . It was continued in the postoperative period with the same rate till it gets finished . MEASUREMENTS Incidence of PONV , Apfel score , intraoperative opioids used and consumption of rescue antiemetics . MAIN RESULTS Demographic data was statistically similar . Out of total 100 patients , 47 patients ( 47 % ) had PONV . In group D , 14 patients ( 28 % ) had PONV while in group NS , 33 patients ( 66 % ) had PONV within 24h of surgery ( p value 0.001 ) . The incidence of PONV was reduced by 38 % in group D which is significantly lower when compared with that of group NS ( p value 0.001 ) . The consumption of single dose of rescue antiemetics in group D was also reduced by 26 % when compared to that of group NS ( p value 0.002 ) . CONCLUSIONS Perioperative administration of 5 % dextrose in patients undergoing laparoscopic surgery can reduce PONV significantly and even if PONV occurs , the quantity of rescue antiemetics to combat PONV is also reduced significantly |
13,548 | 27,099,544 | Simple educational training can substantially improve physicians ' knowledge relating to COPD diagnosis .
Similarly , a physician inhaler education program can improve attitudes toward inhaler teaching and facilitate its implementation in routine clinical practice s. Spirometry combined with inhaled technique education improves the ability of predominantly nonrespiratory physicians to correctly diagnose COPD , to adequately assess its severity , and to increase the percentage of correct COPD treatment used in a real-life setting | Chronic obstructive pulmonary disease ( COPD ) is a chronic inflammatory lung syndrome , caused by long-term inhalation of noxious gases and particles , which leads to gradual airflow limitation .
All health care professionals who care for COPD patients should have full access to high- quality spirometry testing , as postbronchodilator spirometry constitutes the principal method of COPD diagnosis .
One out of four smokers 45 years or older presenting respiratory symptoms in primary care , have non-fully reversible airflow limitation compatible with COPD and are mostly without a known diagnosis .
Approximately 50.0%-98.3 % of patients are undiagnosed worldwide .
The majority of undiagnosed COPD patients are isolated at home , are in nursing or senior-assisted living facilities , or are present in oncology and cardiology clinics as patients with lung cancers and coronary artery disease .
At this time , the prevalence and mortality of COPD subjects is increasing , rapidly among women who are more susceptible to risk factors . | BACKGROUND S In China , the prevalence of chronic obstructive pulmonary disease ( COPD ) in persons 40 years of age or older is estimated at 8.2 % , but this is likely a substantial underestimate . METHODS Eight secondary hospitals which did n't have spirometries were chosen r and omly in Hunan province of central south China . Physician subjects at these hospitals underwent a one-hour training course on the Chinese COPD guidelines . Physicians answered question naires assessing their knowledge of the guidelines before and after the training session . The mean correct scores of question naires were compared before and after training . Four out of the eight hospitals were given access to spirometry . Eligible patient subjects underwent spirometry testing prior to the physician visit . After seeing the patient , physicians were asked to answer a question naire relating to the diagnosis and severity of COPD . Physicians were then given the results of the spirometry , and asked to answer the same question naire . Physicians ' responses before and after receiving the spirometry results were compared . RESULTS 225 physicians participated in the training session . 207 question naires were completed . Mean scores ( out of 100 ) before and after the training were 53.1 ± 21.7 and 93.3 ± 9.8 , respectively . 18 physicians and 307 patient subjects participated in the spirometry intervention . Based on spirometric results , the prevalence of COPD was 38.8 % . Physicians correctly identified the presence of COPD without spirometric data in 85 cases ( 76.6 % ) ; this increased to 117 cases ( 97.4 % ) once spirometric data were available . Without spirometric data , physicians incorrectly diagnosed COPD in 38 patients ; this decreased to 6 patients once spirometric data were available . Spirometric data also improved the ability of physicians to correctly grade COPD severity . CONCLUSIONS Simple educational training can substantially improve physicians ' knowledge relating to COPD . Spirometry combined with education improves the ability of physicians to diagnose COPD and to assess its severity The aim of this study was to test the hypothesis that use of tiotropium , a new long-acting anticholinergic bronchodilator , would be associated with sustained reduction in lung hyperinflation and , thereby , would improve exertional dyspnoea and exercise performance in patients with chronic obstructive pulmonary disease . A r and omised , double-blind , placebo-controlled , parallel-group study was conducted in 187 patients ( forced expiratory volume in one second 44±13 % pred ) : 96 patients received 18 µg tiotropium and 91 patients received placebo once daily for 42 days . Spirometry , plethysmographic lung volumes , cycle exercise endurance and exertional dyspnoea intensity at 75 % of each patient 's maximal work capacity were compared . On day 42 , the use of tiotropium was associated with the following effects at pre-dose and post-dose measurements as compared to placebo : vital capacity and inspiratory capacity ( IC ) increased , with inverse decreases in residual volume and functional residual capacity . Tiotropium increased post-dose exercise endurance time by 105±40 s ( 21 % ) as compared to placebo on day 42 . At a st and ardised time near end-exercise ( isotime ) , IC , tidal volume and minute ventilation all increased , whilst dyspnoea decreased by 0.9±0.3 Borg scale units . In conclusion , the use of tiotropium was associated with sustained reductions of lung hyperinflation at rest and during exercise . Result ant increases in inspiratory capacity permitted greater expansion of tidal volume and contributed to improvements in both exertional dyspnoea and exercise endurance BACKGROUND COPD ranks within the top three causes of mortality in the global burden of disease , yet it remains largely underdiagnosed . We assessed the underdiagnosis of COPD and its determinants in national and international surveys of general population s. METHODS We analyzed representative sample s of adults aged ≥ 40 years r and omly selected from well-defined administrative areas worldwide ( 44 sites from 27 countries ) . Postbronchodilator FEV1/FVC < lower limit of normal ( LLN ) was used to define chronic airflow limitation consistent with COPD . Undiagnosed COPD was considered when participants had postbronchodilator FEV1/FVC < LLN but were not given a diagnosis of COPD . RESULTS Among 30,874 participants with a mean age of 56 years , 55.8 % were women , and 22.9 % were current smokers . Population prevalence of ( spirometrically defined ) COPD ranged from 3.6 % in Barranquilla , Colombia , to 19.0 % in Cape Town , South Africa . Only 26.4 % reported a previous lung function test , and only 5.0 % reported a previous diagnosis of COPD , whereas 9.7 % had a postbronchodilator FEV1/FVC < LLN . Overall , 81.4 % of ( spirometrically defined ) COPD cases were undiagnosed , with the highest rate in Ile-Ife , Nigeria ( 98.3 % ) and the lowest rate in Lexington , Kentucky ( 50.0 % ) . In multivariate analysis , a greater probability of underdiagnosis of COPD was associated with male sex , younger age , never and current smoking , lower education , no previous spirometry , and less severe airflow limitation . CONCLUSIONS Even with substantial heterogeneity in COPD prevalence , COPD underdiagnosis is universally high . Because effective management strategies are available for COPD , spirometry can help in the diagnosis of COPD at a stage when treatment will lead to better outcomes and improved quality of life OBJECTIVE To determine the quality of spirometry performed in primary care practice and to assess the impact of formal training . DESIGN R and omized , controlled prospect i ve interventional study . SETTING Primary care practice , Auckl and City , New Zeal and . PARTICIPANTS Thirty r and omly selected primary care practice s r and omized to " trained " or " usual " groups . One doctor and one practice nurse were nominated to participate from each practice . INTERVENTIONS " Trained " was defined as participation in an " initial " spirometry workshop at week 0 and a " maintenance of st and ards " workshop at week 12 . " Usual " was defined as no formal training until week 12 , when participants they attended the same " initial " workshop provided for the trained group . The study duration was 16 weeks . Each practice was provided with a spirometer to be used at their clinical discretion . MEASUREMENTS AND RESULTS Spirometry data were uploaded weekly and analyzed using American Thoracic Society ( ATS ) criteria for acceptability and reproducibility . The workshops were assessed objective ly with practical and written assessment s , confirming a significant training effect . However , analysis of spirometry performed in clinical practice by the trained practitioners revealed three acceptable blows in only 18.9 % of patient tests . In comparison , 5.1 % of patient tests performed by the usual practitioners had three acceptable blows ( p<0.0001 ) . Only 13.5 % of patient tests in the trained group and 3.4 % in the usual group ( p<0.0001 ) satisfied full acceptability and reproducibility criteria . However , 33.1 % and 12.5 % of patient tests in the trained and usual groups , respectively ( p<0.0001 ) , achieved at least two acceptable blows , the minimum requirement . Nonacceptability was largely ascribable to failure to satisfy end-of-test criteria ; a blow of at least 6 s. Visual inspection of the results of these blows as registered on the spirometer for the presence of a plateau on the volume-time curve suggests that < 15 % were acceptable . CONCLUSIONS Although a significant training effect was demonstrated , the quality of the spirometry performed in clinical practice did not generally satisfy full ATS criteria for acceptability and reproducibility . Further study would be required to determine the clinical impact . However , the ATS guidelines allow for the use of data from unacceptable or nonreproducible maneuvers at the discretion of the interpreter . Since most of the failures were end-of-test related , the FEV1 levels are likely to be valid . Our results serve to emphasize the importance of effective training and quality assurance programs to the provision of successful spirometry in primary care practice Unreported chronic obstructive pulmonary disease ( COPD ) exacerbations are common , but their intermediate-to-long-term impacts on health-related quality of life ( HRQoL ) are unknown . The aim of the present study was to examine the impact of unreported exacerbations on HRQoL at 1 yr . A multicentric prospect i ve cohort study in 491 COPD patients was conducted in China . HRQoL was measured using the St George 's Respiratory Question naire ( SGRQ ) . Other measurements included sociodemographic , clinical , psychosocial and treatment profiles . Patients were monitored monthly for 12 months to document exacerbations ( at least one symptom worsening for ≥48 h ) . Patients were categorised into six groups : no exacerbation , one unreported exacerbation only , more than one unreported exacerbation only , one reported exacerbation only , more than one reported exacerbation only , and both unreported and reported exacerbations . Generalised estimating equations were used to estimate the adjusted associations between exacerbations and HRQoL change . A total of 466 unreported and 410 reported exacerbations were recorded . Compared with patients with no exacerbations , the change in SGRQ total score was similar amongst patients with one unreported exacerbation ( adjusted mean change 1.22 points ( 95 % CI -4.05–6.48 ) ) , but significantly worse among patients with more than one unreported exacerbation ( 4.61 ( 95 % CI 0.09–9.13 ) ) . Development and evaluation of self-management programmes emphasising early recognition of exacerbations and consequent action appear to be warranted BACKGROUND Patients with chronic obstructive pulmonary disease ( COPD ) and asthma depend on inhalers for management , but critical errors committed during inhaler use can limit drug effectiveness . Outpatient education in inhaler technique remains inconsistent due to limited re sources and inadequate provider knowledge . OBJECTIVE To determine whether a simple , two-session inhaler education program can improve physician attitudes toward inhaler teaching in primary care practice . METHODS An inhaler education program with small-group h and s-on device training was instituted for family physicians ( FP ) in British Columbia and Alberta . Sessions were spaced one to three months apart . All critical errors were corrected in the first session . Question naires surveying current inhaler teaching practice s and attitudes toward inhaler teaching were distributed to physicians before and after the program . RESULTS Forty-one ( 60 % ) of a total 68 participating FPs completed both before and after program question naires . Before the program , only 20 ( 49 % ) reported providing some form of inhaler teaching in their practice s , and only four ( 10 % ) felt fully competent to teach patients inhaler technique . After the program , 40 ( 98 % ) rated their inhaler teaching as good to excellent . Thirty-four ( 83 % ) reported providing inhaler teaching in their practice s , either by themselves or by an allied health care professional they had personally trained . All stated they could teach inhaler technique within 5 min . Observation of FPs during the second session by certified respiratory educators found that none made critical errors and all had excellent technique . CONCLUSION A physician inhaler education program can improve attitudes toward inhaler teaching and facilitate implementation in clinical practice BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is characterized by an incompletely reversible limitation in airflow . A physiological variable -- the forced expiratory volume in one second (FEV1)--is often used to grade the severity of COPD . However , patients with COPD have systemic manifestations that are not reflected by the FEV1 . We hypothesized that a multidimensional grading system that assessed the respiratory and systemic expressions of COPD would better categorize and predict outcome in these patients . METHODS We first evaluated 207 patients and found that four factors predicted the risk of death in this cohort : the body-mass index ( B ) , the degree of airflow obstruction ( O ) and dyspnea ( D ) , and exercise capacity ( E ) , measured by the six-minute-walk test . We used these variables to construct the BODE index , a multidimensional 10-point scale in which higher scores indicate a higher risk of death . We then prospect ively vali date d the index in a cohort of 625 patients , with death from any cause and from respiratory causes as the outcome variables . RESULTS There were 25 deaths among the first 207 patients and 162 deaths ( 26 percent ) in the validation cohort . Sixty-one percent of the deaths in the validation cohort were due to respiratory insufficiency , 14 percent to myocardial infa rct ion , 12 percent to lung cancer , and 13 percent to other causes . Patients with higher BODE scores were at higher risk for death ; the hazard ratio for death from any cause per one-point increase in the BODE score was 1.34 ( 95 percent confidence interval , 1.26 to 1.42 ; P<0.001 ) , and the hazard ratio for death from respiratory causes was 1.62 ( 95 percent confidence interval , 1.48 to 1.77 ; P<0.001 ) . The C statistic for the ability of the BODE index to predict the risk of death was larger than that for the FEV1 ( 0.74 vs. 0.65 ) . CONCLUSIONS The BODE index , a simple multidimensional grading system , is better than the FEV1 at predicting the risk of death from any cause and from respiratory causes among patients with COPD CONTEXT Primary care physicians provide care for the majority of patients with mild-to-moderate chronic obstructive pulmonary disease ( COPD ) . Although clinical practice guidelines have been developed for COPD , their influence on primary care practice is unclear . OBJECTIVE To examine primary care decision making , perceptions , and educational needs relating to COPD . DESIGN A survey centered on COPD case-vignettes was developed and distributed to a r and om sample of physicians in adult primary care specialties . RESULTS From 943 respondents , 784 practicing primary care physicians were used in analysis . On average , physicians estimated that 12 % of their patients had COPD . Although 55 % of physicians were aware of major COPD guidelines , only 25 % used them to guide decision-making . Self-identified guidelines showed that users were more likely to order spirometry for subtle respiratory symptoms ( 74 % vs 63 % , P < .01 ) , to initiate therapy for mild symptoms ( 86 % vs. 77 % , P < .01 ) , and to choose long-acting bronchodilators for persistent dyspnea ( 50 % vs 32 % , P < .01 ) . CONCLUSIONS Practice guidelines and CME programs are both valued re sources , but have not yet adequately reached many physicians . Because guidelines appear to influence clinical decision-making , efforts to disseminate them more broadly are needed . Future education should present COPD assessment algorithms tailored to primary care setting s , assess and strengthen spirometry interpretation skills , and discuss a reasoned approach to medication management . Patient-centered content that accurately reflects the nature of primary care practice may enhance physician 's learning experience . Internet-based and distance learning formats may be essential for reaching physicians in many high-need areas Background This study aim ed to evaluate whether incidental CT findings of emphysema , airway thickening and bronchiectasis , as seen on CT scans performed for other non-pulmonary clinical indications , are associated with future acute exacerbations of COPD result ing in hospitalisation or death . Methods This multicentre prospect i ve case – cohort study comprised 6406 subjects who underwent routine diagnostic chest CT for non-pulmonary indications . Using a case – cohort approach , we visually grade d CT scans from cases and a r and om sample of ∼10 % of the baseline cohort ( n=704 ) for emphysema severity ( range 0–20 ) , airway thickening ( range 0–5 ) and bronchiectasis ( range 0–5 ) . We used weighted Cox proportional hazards analysis to assess the independent association between CT findings and hospitalisation or death due to COPD exacerbation . Results During a median follow-up of 4.4 years ( maximum 5.2 years ) , 338 COPD events were identified . The risk of experiencing a future acute exacerbation of COPD result ing in hospitalisation or death was significantly increased in subjects with severe emphysema ( score ≥7 ) and severe airway thickening ( score ≥3 ) . The respective HRs were 4.6 ( 95 % CI 3.0 to 7.1 ) and 5.9 ( 95 % CI 3.4 to 10.5 ) . Severe bronchiectasis ( score ≥3 ) was not significantly associated with increased risk of adverse events ( HR 1.5 ; 95 % CI 0.9 to 2.5 ) . Conclusions Morphological correlates of COPD such as emphysema and airway thickening detected on CT scans obtained for other non-pulmonary indications are strong independent predictors of subsequent development of acute exacerbations of COPD result ing in hospitalisation or death BACKGROUND Community pharmacies ( CP ) have access to subjects at high-risk of suffering Chronic Obstructive Pulmonary Disease ( COPD ) . We investigated if a COPD case finding program in CP could be a new strategy to reduce COPD underdiagnosis . METHODS Prospect i ve , cross-sectional , descriptive , uncontrolled , remotely supported study in 100 CP in Barcelona , Spain . Pharmacists were trained in a four-day workshop on spirometry and COPD , and each was provided with a spirometer for 12 weeks . The program included question naires and forced spirometry measurements , whose quality was controlled and monitored by web-assistance . FINDINGS Overall 2295 ( 73.5 % ) , of 3121 CP customers invited to participate in the program accepted , and 1.456 ( 63.4 % ) were identified as " high risk " for COPD using the GOLD question naire . Only 33 could not conduct spirometry , and a pre-bronchodilator airflow limitation ( FEV1/FVC ratio < 0.7 ) was confirmed in 282 ( 19.8 % ) ; 244 of these were referred to their primary care ( PC ) physician for further diagnostic and therapeutic work-up , but only 39 of them ( 16 % ) fed-back this information to the pharmacist . Clinical ly acceptable quality spirometries ( grade A or B ) were obtained in 69.4 % of the cases . CONCLUSION This study shows that adequately trained and supported community pharmacists can effectively identify individuals at high risk of having COPD and can thus contribute to ameliorate underdiagnosis in this disease . Links between PC and CP should be improved to achieve a useful program Abstract The prevalence of COPD is high , and most cases remain undiagnosed . In contrast , some patients labeled and treated as COPD do not have spirometric confirmation . Our objective was to determine the prevalence of COPD among smokers aged 45 years or older and investigate the accuracy of diagnosis of COPD in primary care . A population -based , epidemiological study was conducted in a primary care centre among subjects older than 45 years with a history of smoking . The participants underwent a clinical question naire and spirometry with bronchodilator test . Additionally , participants with newly diagnosed COPD , defined as postbronchodilator FEV1/FVC<0.7 , underwent 4-week treatment with formoterol and budesonide to rule out reversible airflow obstruction . A total of 1,738 individuals ( 84.4 % male ) with a mean age of 59.9 years were included . The prevalence of COPD was 24.3 % ( 95 % , CI 22.3–26.4 ) , with an overall underdiagnosis of 56.7 % . Patients with COPD were older , more frequently male , with a lower body mass index , a longer history of smoking , lower educational level , previous occupational exposure , and more cardiovascular co-morbidity ( all p < 0.001 ) . After 4 weeks of treatment , 16 % of initially obstructed patients had normal spirometry ; in addition , 15.6 % of individuals with a diagnosis of COPD did not have airflow obstruction . One out of four smokers 45 years or older presenting in primary care have airflow obstruction , mostly undiagnosed . However , among those with an initial diagnosis of COPD up to 16 % will normalise spirometry after 4 weeks of treatment . There is also a significant number of individuals misdiagnosed with COPD BACKGROUND The ' frequent exacerbator ' is recognised as an important phenotype in COPD . Current underst and ing about this phenotype comes from prospect i ve longitudinal clinical trials in secondary /tertiary care with little information reported in primary care population s. AIMS To characterize the frequent-exacerbator phenotype and identify associated risk factors in a large UK primary care COPD population . METHODS Using a large data base of primary care patients from 80 UK general practice s , patients were categorised using GOLD 2014 criteria into high and low risk groups based on exacerbation history . A multivariate logistic regression model was used to investigate covariates associated with the frequent-exacerbator phenotype and risk of experiencing a severe exacerbation ( leading to hospitalisation ) . RESULTS Of the total study population ( n = 9219 ) , 2612 ( 28 % ) fulfilled the criteria for high risk frequent-exacerbators . Independent risk factors ( adjusted odds ratio [ 95 % CI ] ) for ≥2 exacerbations were : most severely impaired modified Medical Research Council ( mMRC ) dyspnoea score ( mMRC grade 4 : 4.37 [ 2.64 - 7.23 ] ) , lower FEV1 percent predicted ( FEV1 < 30 % : 2.42 [ 1.61 - 3.65 ] ) , co-morbid cardiovascular disease ( 1.42 [ 1.19 - 1.68 ] ) , depression ( 1.56 [ 1.22 - 1.99 ] ) or osteoporosis ( 1.54 [ 1.19 - 2.01 ] ) , and female gender ( 1.20 [ 1.01 - 1.43 ] ) . Older patients ( ≥75 years ) , those with most severe lung impairment ( FEV1 < 30 % ) , those with highest mMRC score and those with co-morbid osteoporosis were identified as most at risk of experiencing exacerbations requiring hospitalisation . CONCLUSIONS Although COPD exacerbations occur across all grade s of disease severity , female patients with high dyspnoea scores , more severely impaired lung function and co-morbidities are at greatest risk . Elderly patients , with severely impaired lung function , high mMRC scores and osteoporosis are associated with experience of severe exacerbations requiring hospitalisation OBJECTIVES To examine whether the Global Initiative for Chronic Obstructive Pulmonary Disease ( GOLD ) 2013 revision offers greater predictive ability than the body mass index , airflow obstruction , dyspnea , and exacerbations ( BODEx ) index in elderly adults with chronic obstructive pulmonary disease ( COPD ) . DESIGN Prospect i ve cohort study . SETTING University-affiliated medical center . PARTICIPANTS Taiwanese out patients with COPD ( N = 354 ) . MEASUREMENTS Participants were classified as Group A ( low risk with mild dyspnea ) , Group B ( low risk with more-severe dyspnea ) , Group C ( high risk with mild dyspnea ) , and Group D ( high risk with more-severe dyspnea ) for GOLD 2013 and from Quartile 1 ( 0 - 2 points ) to 4 ( 7 - 9 points ) for BODEx score . Ability to predict exacerbations and mortality was compared using logistic regression analysis with receiver operating characteristic ( ROC ) curve estimations and area under the ROC curve ( AUC ) . RESULTS Mortality was 14.1 % for GOLD Group A , 14.5 % for Group B , 6.5 % for Group C , and 35.8 % for Group D and 15.2 % for BODEx Quartile 1 , 22.5 % for Quartile 2 , 28.1 % for Quartile 3 , and 79.2 % for Quartile 4 . Risk of exacerbation relative to Group A was 1.7 ( 95 % confidence interval ( CI ) = 0.6 - 4.3 ) for Group B , 14.1 ( 95 % CI = 4.6 - 43.2 ) for Group C , and 17.9 ( 95 % CI = 7.6 - 42.0 ) for Group D. The AUC for the GOLD classification and BODEx index were 0.65 and 0.67 for mortality ( P = .60 ) and 0.79 and 0.73 for exacerbation ( P = .03 ) . CONCLUSION The GOLD 2013 classification performed well in identifying individuals at risk of exacerbations , and its predictive ability for exacerbations was better than that of the BODEx index , although the predictive ability for mortality in elderly adults with COPD was poor for both indices CONTEXT AND OBJECTIVE Chronic obstructive pulmonary disease ( COPD ) is a respiratory disease of high prevalence and socioeconomic impact worldwide . It affects approximately 16 % of the population of São Paulo . The incidence of COPD is still unknown in Brazil . The aim of this study was to estimate new cases of COPD in a population -based sample in São Paulo , Brazil , using three different spirometric diagnostic criteria , and to assess the concordance between these criteria . DESIGN AND SETTING Prospect i ve cohort study , in the city of São Paulo , Brazil . METHODS A question naire was applied and anthropometry and pre and post-bronchodilator spirometry were performed on the same subjects as in the initial PLATINO study ( 2003 ) in São Paulo . Data from this follow-up study were added to the original data base of the initial phase . Incident COPD cases refer to subjects who developed the disease in accordance with each spirometric criterion during the nine-year follow-up period . The Statistical Package for the Social Sciences , version 17.0 ( SPSS Inc. , Chicago , IL , USA ) was used in the analysis and the significance level was set at P < 0.05 . RESULTS 613 subjects participated in the follow-up . New COPD cases ranged in frequency from 1.4 % to 4.0 % , depending on the diagnostic criterion used . The concordance between the criteria ranged from 35 % to 60 % . CONCLUSION The incidence of COPD after a nine-year follow-up was high , but varied according to the spirometric criterion used . The agreement between the criteria for identifying new cases of the disease ranged from 35 % to 60 % BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is frequently misdiagnosed or undiagnosed , which can delay disease management interventions . PURPOSE The Screening , Evaluating and Assessing Rate CHanges of diagnosing respiratory conditions in primary care 1 ( SEARCH 1 ) study assessed whether screening using the COPD Population Screener ( COPD -PS ) question naire to detect COPD risk factors and symptoms , with or without a h and held spirometer ( copd -6 ) to detect airflow limitation , can increase yields of COPD diagnosis and respiratory-related clinician actions in primary care . DESIGN A prospect i ve , multi-center , pragmatic , comparative-effectiveness , cluster-r and omized study conducted from September 2010 to October 2011 ( data analyzed from December 2011 to January 2013 ) . PARTICIPANTS Men and women aged ≥40 years visiting their participating primary care practice for any reason . INTERVENTION Practice s were r and omized to three study arms : COPD -PS + copd -6 , COPD -PS alone , and usual care ( no interventions ) . No practice s received any specific education about COPD or its diagnosis . MAIN OUTCOME MEASURES The primary endpoint was yield of new clinical COPD diagnosis ; the secondary endpoint was yield of respiratory-related clinician actions . RESULTS Of 9,704 patients enrolled , 8,770 had no prior COPD diagnosis and were included in endpoint analyses . Both interventions significantly increased COPD diagnostic yield over 8 weeks . Compared with a mean yield of 0.49 % ( 0.13 % ) ( controls ) , yields were 1.07 % ( 0.20 % ) ( OR=2.20 , 95 % CI=1.26 , 3.84 , p=0.006 ) and 1.16 % ( 0.22 % ) ( OR=2.38 , 95 % CI=1.38 , 4.13 , p=0.002 ) for COPD -PS and COPD -PS+ copd -6 study arms , respectively . Respiratory-related clinician actions were not significantly different across study arms . CONCLUSIONS Office-based assessment can significantly increase COPD diagnosis by primary care physicians . Future trials must evaluate whether screening can improve outcomes for patients with COPD |
13,549 | 25,246,802 | Although ATO-based combination treatment was well tolerated by most patients , most trials found that ATO has limited effects on MM patients . | Multiple myeloma ( MM ) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulin .
Although some newly approved drugs ( thalidomide , lenalidomide , and bortezomib ) demonstrate significant benefit for MM patients with improved survival , all MM patients still relapse .
Arsenic trioxide ( ATO ) is the most active single agent in acute promyelocytic leukemia , the antitumor activity of which is partly dependent on the production of reactive oxygen species .
Due to its multifaceted effects observed on MM cell lines and primary myeloma cells , Phase I/II trials have been conducted in heavily pretreated patients with relapsed or refractory MM .
Therapy regimens varied dramatically as to the dosage of ATO and monotherapy versus combination therapy with other agents available for the treatment of MM . | Despite aggressive and innovative therapy , patients with multiple myeloma ( MM ) invariably relapse and die of their disease . New options for non‐cytotoxic salvage therapy and additional therapeutic strategies are needed . Arsenic trioxide , an antitumour agent with a multifaceted mechanism of action , induces apoptosis in vitro in MM cell lines and freshly isolated cells from MM patients and , in preliminary studies , displayed clinical activity in patients with late‐stage MM . A phase 2 , multicentre , open‐label study of arsenic trioxide was conducted in 24 MM patients ; eight had relapsed and 16 were refractory to prior therapy . Patients received arsenic trioxide 0·25 mg/kg/d for 5 d/week during the first 2 weeks of each 4‐week cycle . Sixteen patients had grade 3 or 4 neutropenia and one required antibiotics . Reductions ( 25 % or more ) in serum M‐protein levels occurred in eight of 24 ( 33 % ) patients . An additional six ( 25 % ) patients had stable disease . The median time to response was 67·5 d , with a median duration of response of 130 d. Arsenic trioxide therapy lowered serum creatinine levels in two patients with high baseline values . These data indicate that arsenic trioxide is active and reasonably well tolerated as a single‐agent salvage therapy , even in patients with late‐stage , relapsed and refractory MM In patients with multiple myeloma , there is pre clinical justification to combine arsenic trioxide ( ATO and As(2)O(3 ) ) with DVd ( Doxiltrade mark , vincristine , and dexamethasone ) for newly diagnosed patients . Eleven patients on this phase II trial received 0.15 mg/kg of ATO for five consecutive days followed by four cycles of DVd plus ATO with the ATO at 0.25mg/kg IV twice per week . The most common grade 3 toxicities were hyperglycemia , hyponatremia , and hypocalcemia . There were four partial and no complete responses . We could not demonstrate that the addition of ATO with this schedule improved the response rate of MM to DVd Arsenic has been used since ancient times as a therapeutic agent . However , until recently its use in modern medicine has been restricted to the treatment of a limited number of parasitic infections . In the early 1990s , reports from China described impressive results with arsenic trioxide in patients with de novo , relapsed , and refractory acute promyelocytic leukemia ( APL ) . Other investigators subsequently confirmed these results leading to approval of its use for relapsed or refractory APL in the United States . Investigations of this agent have demonstrated that its efficacy in APL and pre clinical tumor models is dependent upon a number of mechanisms , including induction of apoptosis , effects on cellular differentiation , cell cycling , and tumor angiogenesis . Subsequent pre clinical studies showed significant activity of arsenic trioxide in multiple myeloma ( MM ) . Based on this , in a phase II trial , we have evaluated the activity of arsenic trioxide in 14 patients with relapsed MM , refractory to conventional salvage therapy . With the dose and schedule used , treatment with arsenic trioxide produced responses in three patients and prolonged stable disease in a fourth patient , with the longest response lasting 6 weeks . Although treatment was reasonably well tolerated , in these patients with extensive prior therapy , 11 developed cytopenia , five associated with infectious complications and three developed deep vein thromboses . The results of this small trial support further investigation of this novel drug for the treatment of patients with relapsed or refractory MM Multiple myeloma ( MM ) characterized by proliferation of plasma cells in bone marrow and production of monoclonal immunoglobulin 's . Recently , arsenic trioxide ( ATO ) , has been considered for treatment refractory MM . We assessed the safety and efficacy of ATO for patients with refractory MM . A phase 2 , study of arsenic trioxide was conducted in 12 MM patients , whose refractory to two st and ard therapy . Patients received arsenic trioxide , 0.25 mg/kg/d for 5 d/week during the first 2 consecutive weeks of each 4-week cycle with 2 week rest . Patients who completed one 4-week cycle were evaluated for response to treatment . Twelve patients with refractory multiple myeloma received ATO . Disease assessment was based the amount of serum proteins electrophoresis . Of the10 patients ; stable disease was observed in four patients ( 33 % ) , progression disease in five patients ( 41.6 % ) , complete response in one patient ( 3.8 % ) and the remaining two patients could not be assessed for a response ( because of increased liver enzymes after the first week ) . Some adverse events : increase liver enzymes and serum creatinine , neutropenia , pruritus , nausea , vomiting , lower extremities edema , noninfectious diarrhea was observed . These results indicate that ATO is active and well tolerated as a single-agent salvage therapy , even in patients with late-stage , refractory MM We assessed the safety and efficacy of melphalan , arsenic trioxide ( ATO ) and ascorbic acid ( AA ) ( MAC ) combination therapy for patients with multiple myeloma ( MM ) who failed more than two different prior regimens . Patients received melphalan ( 0·1 mg/kg p.o . ) , ATO ( 0·25 mg/kg i.v . ) and AA ( 1 g i.v ) on days 1–4 of week 1 , ATO and AA twice weekly during weeks 2–5 and no treatment during week 6 of cycle 1 ; during cycles 2–6 , the schedule remained the same except ATO and AA were given twice weekly in week 1 . Objective responses occurred in 31 of 65 ( 48 % ) patients , including two complete , 15 partial and 14 minor responses . Median progression‐free survival and overall survival were 7 and 19 months respectively . Twenty‐two patients had elevated serum creatinine levels ( SCr ) at baseline , and 18 of 22 ( 82 % ) showed decreased SCr levels during treatment . Specific grade 3/4 haematological ( 3 % ) or cardiac adverse events occurred infrequently . Frequent grade 3/4 non‐haematological adverse events included fever/chills ( 15 % ) , pain ( 8 % ) and fatigue ( 6 % ) . This steroid‐free regimen was effective and well tolerated in this heavily pretreated group . These results indicate that the MAC regimen is a new therapeutic option for patients with relapsed or refractory MM Arsenic trioxide ( ATO ) is synergistic with ascorbic acid ( AA ) and melphalan against myeloma both in vitro and in vivo . The aim of this r and omized phase II trial was to determine the safety and efficacy of a combination of ATO , melphalan , and AA as preparative regimen in 48 patients undergoing autologous hematopoietic stem cell transplantation ( ASCT ) for multiple myeloma ( MM ) . Forty-eight patients received melphalan 200 mg/m2 i.v . over 2 days and AA 1000 mg i.v . over 7 days in 3 treatment arms : no ATO ( arm 1 ) , ATO 0.15 mg/kg i.v . x 7 days ( arm 2 ) , and ATO 0.25 mg/kg i.v . x 7 days ( arm 3 ) . No dose-limiting toxicity , engraftment failure , or nonrelapse mortality ( NRM ) was seen in the first 100 days post-ASCT . Complete responses ( CR ) were seen in 12 of 48 patients ( 25 % ) , with an overall response rate ( ORR = CR + PR ) of 85 % . Median progression-free survival ( PFS ) was 25 months ; median overall survival ( OS ) has not yet been reached . There was no significant difference in CR , PFS , or OS among the 3 treatment arms , and no adverse effect of ATO on melphalan pharmacokinetics . Addition of ATO + AA to high-dose melphalan is safe and well tolerated as a preparative regimen for MM Purpose : This Phase I study assessed the feasibility of concomitant arsenic trioxide ( ATO ) , ascorbic acid ( AA ) , and bortezomib ( Velcade ™ ) ( AAV ) for patients with relapsed/refractory multiple myeloma . Experimental Design : ATO ( 0.25 mg/kg ) and AA ( 1 g ) were given with an escalating dose of bortezomib ( 1 mg/m2 or 1.3 mg/m2 IV bolus on days 1 and 8 of a 21-day cycle ) . Results : Ten patients ( median age 62 years ) , with a median of 3 prior regimens , were enrolled . Four ( 40 % ) patients achieved clinical benefit , with one patient achieving a durable partial response . No formal DLTs were encountered . Conclusion : AAV combination was feasible and demonstrated some benefits in this heavily pretreated population Arsenic trioxide ( As2O3 ) is a known environmental toxicant and potent chemotherapeutic agent . Significant correlation has been reported between arsenic exposure ( including consumption of arsenic-contaminated water and clinical use of As2O3 ) and dysfunction in the nervous system . In this study , we aim ed to eluci date the effect of resveratrol with neuroprotective activities on As2O3-induced oxidative damage and cerebral cortex injury . Twenty-four healthy Chinese Dragon Li cats of either sex were r and omly divided into four groups : control ( 1 ml/kg physiological saline ) , As2O3 ( 1 mg/kg ) , resveratrol ( 3 mg/kg ) and As2O3 ( 1 mg/kg ) + resveratrol ( 3 mg/kg ) . As2O3+resveratrol-treated group were given resveratrol ( 3 mg/kg ) 1 h before As2O3 ( 1 mg/kg ) administration . Pretreatment with resveratrol upregulated the activities of antioxidant enzymes and attenuated As2O3-induced increases in reactive oxygen species and malondialdehyde production . In addition , resveratrol attenuated the As2O3-induced reduction in the level of reduced glutathione and the ratio of reduced glutathione to oxidised glutathione , and accumulation of arsenic in the cerebral cortex . These findings support neuroprotective effect of resveratrol on As2O3 toxicity in feline brain and provide a better underst and ing of the mechanism that resveratrol modulates As2O3-induced oxidative damage and a stronger rational for clinical use of resveratrol to protect brain against the toxicity of arsenic The therapeutic effect of arsenic trioxide ( As2O3 ) in the treatment of acute promyelocytic leukemia ( APL ) was evaluated among 15 APL patients at relapse after all-trans retinoic acid ( ATRA ) induced and chemotherapy maintained complete remission ( CR ) . As2O3 was administered intravenously at the dose of 10 mg/d . Clinical CR was achieved in nine of 10 ( 90 % ) patients treated with As2O3 alone and in the remaining five patients treated by the combination of As2O3 and low-dose chemotherapeutic drugs or ATRA . During the treatment with As2O3 , there was no bone marrow depression and only limited side effects were encountered . Pharmacokinetic studies , which were performed in eight patients , showed that after a peak level of 5.54 micromol/L to 7.30 micromol/L , plasma arsenic was rapidly eliminated , and the continuous administration of As2O3 did not alter its pharmacokinetic behaviors . In addition , increased amounts of arsenic appeared in the urine , with a daily excretion accounting for approximately 1 % to 8 % of the total daily dose administered . Arsenic contents in hair and nail were increased , and the peak content of arsenic could reach 2.5 to 2.7 microg/g tissue at CR . On the other h and , a decline of the arsenic content in hair and nail was observed after withdrawal of the drug . We conclude that As2O3 treatment is an effective and relatively safe drug in APL patients refractory to ATRA and conventional chemotherapy Purpose : This multicenter , open-label , phase I/II dose escalation study assessed the safety/tolerability and initial efficacy of arsenic trioxide/bortezomib/ascorbic acid ( ABC ) combination therapy in patients with relapsed/refractory multiple myeloma . Experimental Design : Enrolled in six cohorts , patients were given arsenic trioxide ( 0.125 or 0.250 mg/kg ) , bortezomib ( 0.7 , 1.0 , or 1.3 mg/m2 ) , and a fixed dose of ascorbic acid ( 1 g ) i.v . on days 1 , 4 , 8 , and 11 of a 21-day cycle for a maximum of eight cycles . The primary end point was safety/tolerability of the ABC regimen . Results : Twenty-two patients ( median age , 63 years ) were enrolled , having failed a median of 4 ( range , 3 - 9 ) prior therapies . One occurrence of grade 4 thrombocytopenia was observed . One patient had asymptomatic arrhythmia and withdrew from the study . Objective responses were observed in 6 ( 27 % ) patients , including two partial responses and four minor responses . Median progression-free survival was 5 months ( 95 % confidence interval , 2 - 9 months ) , and median overall survival had not been reached . The 12-month progression-free survival and overall survival rates were 34 % and 74 % , respectively . One ( minor response ) of six patients receiving the lowest dose of bortezomib ( 0.7 mg/m2 ) and 5 ( 2 partial responses and 3 minor responses ) of 16 patients receiving the higher doses ( 1.0 or 1.3 mg/m2 ) responded . Conclusions : The ABC regimen was well tolerated by most patients , and it produced preliminary signs of efficacy with an objective response rate of 27 % in this heavily pretreated study population . These findings warrant further clinical evaluation of the ABC combination for treatment of relapsed/refractory multiple myeloma Bortezomib is active for newly diagnosed and relapsed multiple myeloma , and it has synergistic activity with melphalan . The authors of this report conducted a r and omized trial to determine the safety and efficacy of adding bortezomib to a preparative regimen of arsenic trioxide ( ATO ) , ascorbic acid ( AA ) , and melphalan |
13,550 | 19,738,217 | Sleep domains have been review ed , and several sleep instruments have been identified . | We sought to identify instruments assessing sleep quality that measure the domains of sleep applicable to rheumatoid arthritis ( RA ) patients and are feasible to use and have appropriate reliability , validity , and responsiveness properties . | STUDY OBJECTIVES To develop a sleepiness scale devoid of semantic or geometric elements . DESIGN Subjects were asked to rank in order 7 cartoon faces representing degrees of sleepiness . We used Thurstone 's scaling procedure to transform these rankings into an interval scale , which allowed us to eliminate 2 of the faces . The remaining 5 faces were ranked again using other subjects . In a validation study , subjects rated their perceived level of sleepiness using our scale and other sleepiness scales . Employed shiftworkers and school-going children used our scale to assess its practical applicability . SETTING S Research and diagnostic sleep laboratories , pre- primary to tertiary institutions , shift-working industry . PARTICIPANTS Ethnically diverse healthy and sleep-disordered adults ( n = 490 ) , and school-going children ( n = 345 ) . MEASUREMENTS AND RESULTS Our faces scale correlated with the Karolinska Sleepiness Scale ( P < .05 ) , the Stanford Sleepiness Scale ( P < .04 ) , and a visual analog scale measuring sleepiness ( P < .0001 ) . Shiftworkers showed a time-on-task effect on the evening shift ( P < .0001 ) and a peak in sleepiness at 4:00 and 5:00 ( P < .0001 ) on the night shift . Eight to 10 year old children appeared sleepier than older children throughout a school day ( P < or = .02 ) and became sleepier as the day progressed ( P < .0001 ) . We confirmed that our scale measures sleepiness , uncontaminated by pain , anger , or happiness . CONCLUSIONS We have devised a sleepiness scale suitable for people too young or insufficiently educated to employ more-conventional scales . We envisage the scale being used for diagnostic , therapeutic , and research purpose In this study , the authors sought to determine the effects of length and clarity on response rates and data quality for two food frequency question naires ( FFQs ) : the newly developed 36-page Diet History Question naire ( DHQ ) , design ed to be cognitively easier for respondents , and a 16-page FFQ developed earlier for the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial . The PLCO Trial is a 23-year r and omized controlled clinical trial begun in 1992 . The sample for this sub study , which was conducted from January to April of 1998 , consisted of 900 control and 450 screened PLCO participants aged 55 - 74 years . Controls received either the DHQ or the PLCO FFQ by mail . Screenees , who had previously completed the PLCO FFQ at baseline , were administered the DHQ . Among controls , the response rate for both FFQs was 82 % . Average amounts of time needed by controls to complete the DHQ and the PLCO FFQ were 68 minutes and 39 minutes , respectively . Percentages of missing or uninterpretable responses were similar between instruments for questions on frequency of intake but were approximately 3 and 9 percentage points lower ( p < or = 0.001 ) in the DHQ for questions on portion size and use of vitamin/mineral supplements , respectively . Among screenees , response rates for the DHQ and the PLCO FFQ were 84 % and 89 % , respectively , and analyses of questions on portion size and supplement use showed few differences . These data indicated that the shorter FFQ was not better from the perspective of response rate and data quality , and that clarity and ease of administration may compensate for question naire length The purpose of this study was to develop and test the Verran and Snyder-Halpern ( VSH ) Sleep Scale , an instrument to subjectively measure sleep characteristics . Four major sleep factors and their associated characteristics were proposed for the Sleep Scale . Subjects completed three r and omly ordered sleep question naires on three consecutive weekday mornings within the first two hours after arising . Scales included the VSH Sleep Scale , a sleep question naire and a sleep log . The VSH Sleep Scale had a reliability coefficient of .82 ( theta ) . Construct validity was examined by factor analysis and correlations between Sleep Scale items and corresponding items on the two other study instruments . Scale validity also was assessed by the known groups method . Beginning support for the validity of the VSH Sleep Scale is provided It seems sensible to tailor treatments of insomnia in relation to the presenting characteristics of the sleeper and of the complaint . This report describes the first study formally to examine the comparative effectiveness of tailored and untailored ( r and omly allocated ) treatments . We developed a question naire to facilitate the design ing of individualized programmes . Results indicated that statistical analysis may underestimate the benefits of tailoring . Measures of clinical ly significant change , however , suggested that tailored treatment though it may be highly effective , is no more so than stimulus control therapy Background : Insomnia is a prevalent health complaint that is often difficult to evaluate reliably . There is an important need for brief and valid assessment tools to assist practitioners in the clinical evaluation of insomnia complaints . Objective : This paper reports on the clinical validation of the Insomnia Severity Index ( ISI ) as a brief screening measure of insomnia and as an outcome measure in treatment research . The psychometric properties ( internal consistency , concurrent validity , factor structure ) of the ISI were evaluated in two sample s of insomnia patients . Methods : The first study examined the internal consistency and concurrent validity of the ISI in 145 patients evaluated for insomnia at a sleep disorders clinic . Data from the ISI were compared to those of a sleep diary measure . In the second study , the concurrent validity of the ISI was evaluated in a sample of 78 older patients who participated in a r and omized-controlled trial of behavioral and pharmacological therapies for insomnia . Change scores on the ISI over time were compared with those obtained from sleep diaries and polysomnography . Comparisons were also made between ISI scores obtained from patients , significant others , and clinicians . Results : The results of Study 1 showed that the ISI has adequate internal consistency and is a reliable self-report measure to evaluate perceived sleep difficulties . The results from Study 2 also indicated that the ISI is a valid and sensitive measure to detect changes in perceived sleep difficulties with treatment . In addition , there is a close convergence between scores obtained from the ISI patient 's version and those from the clinician 's and significant other 's versions . Conclusions : The present findings indicate that the ISI is a reliable and valid instrument to quantify perceived insomnia severity . The ISI is likely to be a clinical ly useful tool as a screening device or as an outcome measure in insomnia treatment research As part of the Women 's Health Initiative Study , the 5-item Women 's Health Initiative Insomnia Rating Scale ( WHIIRS ) was developed . This article summarizes the development of the scale through the use of responses from 66,269 postmenopausal women ( mean age = 62.07 years , SD = 7.41 years ) . All women completed a 10-item question naire concerning sleep . A novel resampling technique was introduced as part of the data analysis . Principal-axes factor analysis without iteration and rotation to a varimax solution was conducted for 120,000 r and om sample s of 1,000 women each . Use of this strategy led to the development of a scale with a highly stable factor structure . Structural equation modeling revealed no major differences in factor structure across age and race-ethnic groups . WHIIRS norms for race-ethnicity and age subgroups are detailed The Sleep Disorders Question naire ( SDQ ) is a 176-item question naire design ed to diagnose the presence of common sleep disorders . This study set out to assess the validity of a Dutch translation of the SDQ . Scores on 145 question naires were analyzed . A cluster analysis of these scores revealed the following clusters : healthy , depression , insomnia , narcolepsy , and apnea . The cluster classification proved correct for 67 % of the subjects , as determined on the basis of polysomnography . These results show that the Dutch SDQ is a reasonably valid instrument for diagnosing sleep disorders |
13,551 | 19,815,200 | Innovative community-based strategies combined with health systems strengthening may improve childbirth care for the rural poor , help reduce gross inequities in maternal and newborn survival and stillbirth rates , and provide an effective transition to higher coverage for facility births | BACKGROUND For the world 's 60 million non-facility births , addressing who is currently attending these births and what effect they have on birth outcomes is a key starting point toward improving care during childbirth .
OBJECTIVE We present a systematic review of evidence for the effect of community-based cadres-community-based skilled birth attendants ( SBAs ) , trained traditional birth attendants ( TBAs ) , and community health workers (CHWs)-in improving perinatal and intrapartum-related outcomes . | Various community-based interventions have been proposed to improve maternity care , but hardly any studies have reported the effect of these measures on maternal mortality . In this study , the efficacy of a maternity-care programme to reduce maternal mortality has been evaluated in the context of a primary health-care project in rural Bangladesh . Trained midwives were posted in villages , and asked to attend as many home-deliveries as possible , detect and manage obstetric complications at onset , and accompany patients requiring referral for higher-level care to the project central maternity clinic . The effect of the programme was evaluated by comparison of direct obstetric maternal mortality ratios between the programme area and a neighbouring control area without midwives . R and om assignment of the intervention was not possible but potentially confounding characteristics , including coverage and use of other health and family planning services , were similar in both areas . Maternal mortality ratios due to obstetric complications were similar in both areas during the 3 years preceding the start of the programme . By contrast , during the following 3 years , the ratio was significantly lower in the programme than in the control area ( 1.4 vs 3.8 per 1000 live births , p = 0.02 ) . The findings suggest that maternal survival can be improved by the posting of midwives at village level , if they are given proper training , means , supervision , and back-up . The inputs for such a programme to succeed and the constraints of its replication on a large scale should not be underestimated BACKGROUND Neonatal deaths in developing countries make the largest contribution to global mortality in children younger than 5 years . 90 % of deliveries in the poorest quintile of households happen at home . We postulated that a community-based participatory intervention could significantly reduce neonatal mortality rates . METHODS We pair-matched 42 geopolitical clusters in Makwanpur district , Nepal , selected 12 pairs r and omly , and r and omly assigned one of each pair to intervention or control . In each intervention cluster ( average population 7000 ) , a female facilitator convened nine women 's group meetings every month . The facilitator supported groups through an action-learning cycle in which they identified local perinatal problems and formulated strategies to address them . We monitored birth outcomes in a cohort of 28?931 women , of whom 8 % joined the groups . The primary outcome was neonatal mortality rate . Other outcomes included stillbirths and maternal deaths , uptake of antenatal and delivery services , home care practice s , infant morbidity , and health-care seeking . Analysis was by intention to treat . The study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N31137309 . FINDINGS From 2001 to 2003 , the neonatal mortality rate was 26.2 per 1000 ( 76 deaths per 2899 livebirths ) in intervention clusters compared with 36.9 per 1000 ( 119 deaths per 3226 livebirths ) in controls ( adjusted odds ratio 0.70 [ 95 % CI 0.53 - 0.94 ] ) . Stillbirth rates were similar in both groups . The maternal mortality ratio was 69 per 100000 ( two deaths per 2899 livebirths ) in intervention clusters compared with 341 per 100000 ( 11 deaths per 3226 livebirths ) in control clusters ( 0.22 [ 0.05 - 0.90 ] ) . Women in intervention clusters were more likely to have antenatal care , institutional delivery , trained birth attendance , and hygienic care than were controls . INTERPRETATION Birth outcomes in a poor rural population improved greatly through a low cost , potentially sustainable and scalable , participatory intervention with women 's groups OBJECTIVES In their efforts to reduce maternal and neonatal morbidity and mortality , many national and international agencies make considerable investments in training traditional birth attendants ( TBAs ) . The value of TBA training is controversial , and plausible arguments are made both for and against . Numerous process evaluations are reported in the literature and the results are mixed , though generally positive . Outcome evaluations , however , are scarce . This article describes an outcome evaluation of TBA training conducted in two districts of Brong-Ahafo Region , Ghana , during 1996 . DESIGN AND METHODS Data from a r and om sample survey of 1961 clients of TBAs were subjected to logistic regression modelling to determine the effect of training on maternal outcomes , controlling for other independent variables . RESULTS Of eight outcomes modelled , three were associated with training and five were not . Three additional outcomes were not modelled , primarily due to low prevalence . CONCLUSIONS Despite some inherent design limitations , this study found that the evidence for a beneficial impact of TBA training was not compelling . Training sponsors should consider alternative health investments and , where TBA training remains the intervention of choice , be realistic about expectations of impact BACKGROUND Effective and scalable community-based strategies are needed for identification and management of serious neonatal illness . METHODS As part of a community-based , cluster-r and omized controlled trial of the impact of a package of maternal-neonatal health care , community health workers ( CHWs ) were trained to conduct household surveillance and to identify and refer sick newborns according to a clinical algorithm . Assessment s of newborns by CHWs at home were linked to hospital-based assessment s by physicians , and factors impacting referral , referral compliance and outcome were evaluated . RESULTS Seventy-three per cent ( 7310/10,006 ) of live-born neonates enrolled in the study were assessed by CHWs at least once ; 54 % were assessed within 2 days of birth , but only 15 % were attended at delivery . Among assessment s for which referral was recommended , compliance was verified in 54 % ( 495/919 ) . Referrals recommended to young neonates 0 - 6 days old were 30 % less likely to be complied with compared to older neonates . Compliance was positively associated with having very severe disease and selected clinical signs , including respiratory rate > or = 70/minute ; weak , abnormal or absent cry ; lethargic or less than normal movement ; and feeding problem . Among 239 neonates who died , only 38 % were assessed by a CHW before death . CONCLUSIONS Despite rigorous programmatic effort , reaching neonates within the first 2 days after birth remained a challenge , and parental compliance with referral recommendation was limited , particularly among young neonates . To optimize potential impact , community postnatal surveillance must be coupled with skilled attendance at delivery , and /or a worker skilled in recognition of neonatal illness must be placed in close proximity to the community to allow for rapid case management to avert early deaths OBJECTIVE : We found a high burden of morbidities in a cohort of neonates observed in rural Gadchiroli , India . We hypothesised that interventions would reduce the incidence of neonatal morbidities , including the seasonal increase observed in many of them . This article reports the effect of home-based neonatal care on neonatal morbidities in the intervention arm of the field trial by comparing the early vs late periods , and the possible explanation for this effect . METHODS : During 3 years ( 1995 to 1998 ) , trained village-health-workers ( VHWs ) in 39 villages prospect ively collected data by making home visits during pregnancy , home-delivery and during neonatal period . We estimated the incidence and burden of neonatal morbidities over the 3 years from these data . In the first year , the VHWs made home visits only to observe . From the second year , they assisted mothers in neonatal care and managed the sick neonates at home . Health education of mothers and family members , individually and in group , was added in the third year . We measured the coverage of interventions over the 3 years and evaluated maternal knowledge and practice s on 21 indicators in the third year . The effect on 17 morbidities was estimated by comparing the incidence in the first year with the third year . RESULTS : The VHWs observed 763 neonates in the first year , 685 in the second and 913 in the third year . The change in the percent incidence of morbidities was ( i ) infections , from 61.6 to 27.5 ( −55 % ; p<0.001 ) , ( ii ) care-related morbidities ( asphyxia , hypothermia , feeding problems ) from 48.2 to 26.3 ( −45 % ; p<0.001 ) ; ( iii ) low birth weight from 41.9 to 35.2 ( −16 % ; p<0.05 ) ; ( iv ) preterm birth and congenital anomalies remained unchanged . The mean number of morbidities/100 neonates in the 3 years was 228 , 170 and 115 ( a reduction of 49.6 % ; p<0.001 ) . These reductions accompanied an increasing percent score of interventions during 3 years : 37.9 , 58.4 and 81.3 , thus showing a dose – response relationship . In the third year , the proportion of correct maternal knowledge was 78.7 % and behaviours was 69.7 % . The significant seasonal increase earlier observed in the incidence of five morbidities reduced in the third year . CONCLUSION : The home-based care and health education reduced the incidence and burden of neonatal morbidities by nearly half . The effect was broad , but was especially pronounced on infections , care-related morbidities and on the seasonal increase in morbidities BACKGROUND In rural India , most births take place in the home , where high-risk care practice s are common . We developed an intervention of behaviour change management , with a focus on prevention of hypothermia , aim ed at modifying practice s and reducing neonatal mortality . METHODS We did a cluster-r and omised controlled efficacy trial in Shivgarh , a rural area in Uttar Pradesh . 39 village administrative units ( population 104,123 ) were allocated to one of three groups : a control group , which received the usual services of governmental and non-governmental organisations in the area ; an intervention group , which received a preventive package of interventions for essential newborn care ( birth preparedness , clean delivery and cord care , thermal care [ including skin-to-skin care ] , breastfeeding promotion , and danger sign recognition ) ; or another intervention group , which received the package of essential newborn care plus use of a liquid crystal hypothermia indicator ( ThermoSpot ) . In the intervention clusters , community health workers delivered the packages via collective meetings and two antenatal and two postnatal household visitations . Outcome measures included changes in newborn-care practice s and neonatal mortality rate compared with the control group . Analysis was by intention to treat . This study is registered as International St and ard R and omised Control Trial , number NCT00198653 . FINDINGS Improvements in birth preparedness , hygienic delivery , thermal care ( including skin-to-skin care ) , umbilical cord care , skin care , and breastfeeding were seen in intervention arms . There was little change in care-seeking . Compared with controls , neonatal mortality rate was reduced by 54 % in the essential newborn-care intervention ( rate ratio 0.46 [ 95 % CI 0.35 - 0.60 ] , p<0.0001 ) and by 52 % in the essential newborn care plus ThermoSpot arm ( 0.48 [ 95 % CI 0.35 - 0.66 ] , p<0.0001 ) . INTERPRETATION A socioculturally context ualised , community-based intervention , targeted at high-risk newborn-care practice s , can lead to substantial behavioural modification and reduction in neonatal mortality . This approach can be applied to behaviour change along the continuum of care , harmonise vertical interventions , and build community capacity for sustained development . FUNDING USAID and Save the Children-US through a grant from the Bill & Melinda Gates Foundation This analysis identifies salient features of team management that were critical to the efficiency of program implementation and the effectiveness of behavior change management to promote essential newborn care practice s in Uttar Pradesh , India . In May 2003 , the Johns Hopkins Bloomberg School of Public Health and King George Medical University initiated a cluster-r and omized , controlled neonatal health research program . In less than 2 years , the trial demonstrated rapid adoption of several evidence -based newborn care practice s and a substantial reduction in neonatal mortality in intervention clusters . Existing literature involving research program management in re source -constrained areas of developing countries is limited and fails to provide models for team organization and empowerment . The neonatal research project examined in this paper developed a unique management strategy that provides an effective blueprint for future projects . Transferable learning points from the project include emphasizing a common vision , utilizing a live-in field site office , prioritizing character and potential in the hiring process , implementing a learning-by-doing training program , creating tiers of staff recognition , encouraging staff autonomy , ensuring a broad staff knowledge base to seamlessly h and le absences , and maintaining the flexibility to change partnerships or strategies OBJECTIVE : To assess the ability of midwives to interpret antenatal cards and partograms correctly following completion of the Maternal Care Manual of the Perinatal Education Programme . STUDY DESIGN : We conducted a prospect i ve , controlled trial in a study town and two control towns in the Eastern Cape Province of South Africa . All 93 midwives caring for pregnant women in the three towns were included in the study . Sample s were compared using the two-tailed Student ’s t-test . RESULTS : The marks achieved by the study group for questions from the antenatal card and the partogram improved by 33.0 % ( p < 0.001 ) and 17.5 % ( p = 0.001 ) , respectively . No changes were observed in the control group . CONCLUSION : Midwives that studied the Maternal Care Manual significantly improved their ability to interpret clinical information and apply knowledge . If this ability is applied in clinical practice , a reduction in maternal and perinatal deaths is possible OBJECTIVE to assess the effectiveness of promoting the use of the World Health Organization ( WHO ) partograph by midwives for labour in a maternity home by comparing outcomes after birth . SETTING Medan city , North Sumatera Province , Indonesia . PARTICIPANTS 20 midwives who regularly conducted births in maternity homes , r and omly allocated into two equal groups . DESIGN cluster r and omised-control trial . INTERVENTION under supervision from a team of obstetricians , midwives in the intervention group were introduced to the WHO partograph , trained in its use and instructed to use it in subsequent labours . MEASUREMENTS AND FINDINGS there were 304 eligible women with vertex presentations among 358 labouring women in the intervention group and 322 among 363 in the control group . Among the intervention group , 304 ( 92.4 % ) partographs were correctly completed . From 71 women with the graph beyond the alert line , 42 ( 65 % ) were referred to hospital . Introducing the partograph significantly increased referral rate , and reduced the number of vaginal examinations , oxytocin use and obstructed labour . The proportions of caesarean sections and prolonged labour were not significantly reduced . Apgar scores of less than 7 at 1min was reduced significantly , whereas Apgar scores at 5mins and requirement for neonatal resuscitation were not significantly different . Fetal death and early neonatal death rates were too low to compare . IMPLICATION S FOR PRACTICE a training programme with follow-up supervision and monitoring may be of use when introducing the WHO partograph in other similar setting s , and the findings of this study suggest that the appropriate time of referral needs more emphasis in continuing education . CONCLUSION the WHO partograph should be promoted for use by midwives who care for labouring women in a maternity home The preliminary findings of a prospect i ve study of perinatal , neonatal and maternal mortality carried out in a rural community of Sudan are reported . Out of 6275 deliveries monitored over a period of 3 years , 150 stillbirths , 167 neonatal deaths and 27 maternal deaths were observed . An intervention program to up grade the skills of the village midwives started in the middle of the second year . There was a 25 % reduction in the risk of unfavorable outcome of pregnancy ( i.e. stillbirth and neonatal death ) in the third year relative to the first 2 years . Peer review of the 40 village midwives who took part in the study revealed their tremendous potentials in mobilization of mothers as well as participation in primary health care . Their role in detection of high risk pregnancies and newborns can not be overemphasized OBJECTIVES To determine whether the Maternal Care manual of the Perinatal Education Programme ( PEP ) is effective in improving the cognitive knowledge of midwives . DESIGN A prospect i ve controlled trial in a region where PEP was not previously used . The midwifery knowledge of all midwives caring for pregnant women in the three towns was tested before the commencement of the study . The Maternal Care manual was then introduced to the midwives in he study town and they worked through the programme . Following the completion of the manual , all midwives were tested again with the same test . The time interval between the pre and post testing was 12 months . SETTING Three towns on the Eastern Cape Province of South Africa . PARTICIPANTS All Midwives caring for pregnant women in three towns . INTERVENTIONS The Maternal Care manual of PEP was studied by the midwives in the study town . MEASUREMENTS AND FINDINGS Changes in cognitive knowledge were tested with multiple choice questions . A significant improvement ( p < 0.0001 ) was achieved in the study town . The mean score ( maximum 70 ) improved by 22.4 ( 32 % ) marks , from 35.9 ( 51 % ) to 58.3 ( 83 % ) . KEY CONCLUSIONS The cognitive knowledge of midwives who completed the Maternal Care manual improved significantly . IMPLICATION S FOR PRACTICE These findings are to particular importance as the method by which the Maternal Care manual of PEP was applied conforms to the method suggested for the its national use OBJECTIVE To estimate the validity ( sensitivity , specificity , and positive and negative predictive values ) of a clinical algorithm as used by community health workers ( CHWs ) to detect and classify neonatal illness during routine household visits in rural Bangladesh . METHODS CHWs evaluated breastfeeding and symptoms and signs of illness in 395 neonates selected r and omly from neonatal illness surveillance during household visits on postnatal days 0 , 2 , 5 and 8 . Neonates classified with very severe disease ( VSD ) were referred to a community-based hospital . Within 12 hours of CHW assessment s , physicians independently evaluated all neonates seen in a given day by one CHW , r and omly chosen from among 36 project CHWs . Physicians recorded symptoms and signs of illness , classified the illness , and determined whether the newborn needed referral-level care at the hospital . Physicians ' identification and classification were used as the gold st and ard in determining the validity of CHWs ' identification of symptoms and signs of illness and its classification . FINDINGS CHWs ' classification of VSD showed a sensitivity of 73 % , a specificity of 98 % , a positive predictive value of 57 % and a negative predictive value of 99 % . A maternal report of any feeding problem as ascertained by physician question ing was significantly associated ( P < 0.001 ) with ' not sucking at all ' and ' not attached at all ' or ' not well attached ' as determined clinical ly by CHWs during feeding assessment . CONCLUSION CHWs identified with high validity the neonates with severe illness needing referral-level care . Home-based illness recognition and management , including referral of neonates with severe illness by CHWs , is a promising strategy for improving neonatal health and survival in low-re source developing country setting Maternal morbidity and mortality are high in the Indian context , but the majority of maternal deaths could be avoided by prompt and effective access to intrapartum care ( WHO , 1999 ) . Underst and ing the care seeking responses to intrapartum morbidities is crucial if maternal health is to be effectively improved , and maternal mortality reduced . This paper presents the results of a prospect i ve study of 388 women followed through delivery and traditional postpartum in rural Karnataka in southern India . In this setting , few women use the existing health facilities and most deliveries occur at home . The analysis uses quantitative data , collected via question naires administered to women both during pregnancy and immediately after delivery . By virtue of its prospect i ve design , the study gives a unique insight into intentions for intrapartum care during pregnancy as well as events following morbidities during labour . Routine care in the intrapartum period , both within institutions and at home , and impediments to appropriate care are also examined . The study was design ed to collect information about health seeking decisions made by women and their families as pregnancies unfolded , rather than trying to capture women 's experience from a retrospective instrument . The data set is therefore a rich source of quantitative information , which incorporates details of event sequences and health service utilization not previously collected in a Safe Motherhood study . Additional qualitative information was also available from concurrent in-depth interviews with pregnant women , their families , health care providers and other key informants in the area . The level of unplanned institutional care seeking during the intrapartum period within the study area was very high , increasing from 11 % planning deliveries at a facility to an eventual 35 % actually delivering in hospitals . In addition there was a significant move away from planned deliveries with the auxiliary nurse midwive ( ANM ) , to births with a lay attendant or dai . The proportion of women who planned for an ANM to assist was 49 % , as compared with the actual occurrence , which was less than half of this proportion . Perceived quality of care was found to be an important factor in health seeking behaviour , as was wealth , caste , education and experience of previous problems in pregnancy . Actual care given by a range of practitioners was found to contain both beneficial and undesirable elements . As a response to serious morbidities experienced within the study period , many women were able to seek care although sometimes after a long delay . Those women who experienced inadequate progression of labour pains were most likely to proceed unexpectedly to a hospital delivery The presence of a skilled birth attendant at delivery is important in averting maternal and neonatal mortality and morbidity . It has now shown that even trained traditional birth attendants ( TBAs ) can not , in most cases , save women 's lives effectively because they are unable to treat complications , and are often unable to refer . Qualified midwives and doctors are often not available in the rural areas and community setting s where most women in developing countries deliver . Defining the minimum competency level necessary to meet the definition of skilled birth attendant is important , particularly in countries such as Nepal with limited availability of facility-based emergency obstetric care . Maternal and child health workers are local women aged 18 - 35 who completed a 15-week course in maternal and child health . As the role of MCHWs has exp and ed to meet the country 's needs for skilled attendance , a 6-week " refresher " course in midwifery skills is offered . The results of this clinical skills assessment of 104 r and omly selected MCHWs from 15 districts across Nepal supports the premise that MCHWs with appropriate training have an acceptable level of knowledge and skill , demonstrated in a practice situation , to meet the definition of community level skilled birth attendants . Yet , competency alone will not necessarily improve the situation . To affect maternal mortality in Nepal , MCHWs must be widely available , they must be allowed to do what they are trained to do , and they must have logistical and policy support BACKGROUND A study in Matlab , Bangladesh , has provided evidence favouring a community-based maternity-care delivery system . 3 years of this programme coincided with a significant reduction in direct obstetric mortality compared with the 3 years before the programme . We have examined whether the effects of the programme are sustained over time . METHODS Using data from the continuing demographic survelliance system and from special investigations into the rates and causes of maternal mortality during 1976 - 93 , we compared the trends in direct obstetric maternal mortality ratios in the Maternal and Child Health and Family Planning ( MCH-FP ) area ( which has received extensive services in health and family planning since 1977 ) with those in the comparison area ( with no such intensive health inputs ) . We divided the areas and time periods into discrete groups that best represented the effects of the introduction of the maternity-care programme . FINDINGS Direct obstetric mortality declined by 3 % per year ( rate ratio 0.97 per year [ 95 % CI 0.95 - 0.99 ] ) ; there was no difference between the MCH-FP and comparison areas ( 1.00 [ 0.96 - 1.05 ] ) . Direct obstetric mortality halved between 1976 - 86 and 1987 - 89 in the northern MCH-FP area , where the maternity-care programme was initiated in 1987 ( 0.50 [ 0.22 - 0.99 ] ) , but showed no change in the southern MCH-FP area , which had no such intervention at that time ( 1.07 [ 0.64 - 1.72 ] ) . After 1990 , when the programme was exp and ed throughout the MCH-FP area , the southern part showed a downward ( non-significant ) trend in direct obstetric mortality ( 0.68 [ 0.35 - 1.32 ] ) . However , direct obstetric mortality also declined between 1987 and 1989 in the southern comparison area ( 0.48 [ 0.26 - 0.83 ] ) in the absence of an intense maternity-care programme , and remained stable thereafter . In the northern comparison area , there was no such decline in direct obstetric mortality ( 0.78 [ 0.40 - 1.40 ] ) . INTERPRETATION Although the introduction of the maternity-care programme coincided with declining trends in direct obstetric mortality in the areas covered by the programme , a decline also occurred in one of the areas not receiving any such interventions . Caution is required in the interpretation of short-term trends in one indicator in studies design ed without r and om allocation of interventions into treatment and control groups BACKGROUND Neonatal mortality accounts for a high proportion of deaths in children under the age of 5 years in Bangladesh . Therefore the project for advancing the health of newborns and mothers ( Projahnmo ) implemented a community-based intervention package through government and non-government organisation infrastructures to reduce neonatal mortality . METHODS In Sylhet district , 24 clusters ( with a population of about 20 000 each ) were r and omly assigned in equal numbers to one of two intervention arms or to the comparison arm . Because of the study design , masking was not feasible . All married women of reproductive age ( 15 - 49 years ) were eligible to participate . In the home-care arm , female community health workers ( one per 4000 population ) identified pregnant women , made two antenatal home visits to promote birth and newborn-care preparedness , made postnatal home visits to assess newborns on the first , third , and seventh days of birth , and referred or treated sick neonates . In the community-care arm , birth and newborn-care preparedness and careseeking from qualified providers were promoted solely through group sessions held by female and male community mobilisers . The primary outcome was reduction in neonatal mortality . Analysis was by intention to treat . The study is registered with Clinical Trials.gov , number 00198705 . FINDINGS The number of clusters per arm was eight . The number of participants was 36059 , 40159 , and 37598 in the home-care , community-care , and comparison arms , respectively , with 14 769 , 16 325 , and 15 350 livebirths , respectively . In the last 6 months of the 30-month intervention , neonatal mortality rates were 29.2 per 1000 , 45.2 per 1000 , and 43.5 per 1000 in the home-care , community-care , and comparison arms , respectively . Neonatal mortality was reduced in the home-care arm by 34 % ( adjusted relative risk 0.66 ; 95 % CI 0.47 - 0.93 ) during the last 6 months versus that in the comparison arm . No mortality reduction was noted in the community-care arm ( 0.95 ; 0.69 - 1.31 ) . INTERPRETATION A home-care strategy to promote an integrated package of preventive and curative newborn care is effective in reducing neonatal mortality in communities with a weak health system , low health-care use , and high neonatal mortality This study was design ed to assess the utility and impact on perinatal mortality of a model traditional birth attendant ( TBA ) training program in rural Mozambique by comparing birth attendance and outcomes in similar communities with and without trained TBAs . Birth attendants and pregnancy outcomes were compared in 1 ) communities with good access to trained TBAs , 2 ) r and omly selected , comparable communities with no access to trained TBAs , and 3 ) communities with good access to functioning maternities . Information was collected by interviews with women in r and omly selected households . A total of 4,169 women were interviewed who reported on 3,616 completed pregnancies , which result ed in a birth or fetal death . Among women with good access to trained TBAs , 33 % reported giving birth attended by a trained TBA , 43 % reported giving birth at a health facility , and 24 % reported giving birth attended by an untrained person . Among women without access to trained TBAs , 58 % reported giving birth at health facilities , and 42 % reported attendance by untrained persons . Among women with access to functioning maternity centers , 77 % reported giving birth at a health facility and 22 % said their birth was attended by an untrained person . There was no significant difference in perinatal or infant mortality among the groups . This study demonstrated a preference for health facility deliveries among rural Mozambican women with good access to trained TBAs . It also failed to demonstrate a reduction in perinatal or infant mortality associated with TBA training . Women said they preferred to deliver in health facilities because conditions were considered better and interventions could be performed if needed . The preference for health facility birth over home birth with a TBA may have been related to difficulties with TBA neighbors and their families or fear of potential witchcraft . Efforts to promote TBA training should be balanced with support for birthing services based in health facilities |
13,552 | 25,268,900 | This will increase the generalisability of trial results to the general population . | Cognitive outcomes are frequently implemented as endpoints in nutrition research .
To reduce the number of statistical comparisons it is commonplace for nutrition research ers to combine cognitive test results into a smaller number of broad cognitive abilities .
However , there is a clear lack of underst and ing and consensus as to how best execute this practice .
The present paper review s contemporary models of human cognition and proposes a st and ardised , evidence -based method for grouping cognitive test data into broader cognitive abilities .
Both Carroll 's model of human cognitive ability and the Cattell-Horn-Carroll ( CHC ) model of intelligence provide empirically based taxonomies of human cognition . | BACKGROUND Effects of diet on blood lipids are best known in white men , and effects of type of carbohydrate on triacylglycerol concentrations are not well defined . OBJECTIVE Our goal was to determine the effects of diet on plasma lipids , focusing on subgroups by sex , race , and baseline lipid concentrations . DESIGN This was a r and omized controlled outpatient feeding trial conducted in 4 field centers . The subjects were 436 participants of the Dietary Approaches to Stop Hypertension ( DASH ) Trial [ mean age : 44.6 y ; 60 % African American ; baseline total cholesterol : < or = 6.7 mmol/L ( < or = 260 mg/dL ) ] . The intervention consisted of 8 wk of a control diet , a diet increased in fruit and vegetables , or a diet increased in fruit , vegetables , and low-fat dairy products and reduced in saturated fat , total fat , and cholesterol ( DASH diet ) , during which time subjects remained weight stable . The main outcome measures were fasting total cholesterol , LDL cholesterol , HDL cholesterol , and triacylglycerol . RESULTS Relative to the control diet , the DASH diet result ed in lower total ( -0.35 mmol/L , or -13.7 mg/dL ) , LDL- ( -0.28 mmol/L , or -10.7 mg/dL ) , and HDL- ( -0.09 mmol/L , or -3.7 mg/dL ) cholesterol concentrations ( all P < 0.0001 ) , without significant effects on triacylglycerol . The net reductions in total and LDL cholesterol in men were greater than those in women by 0.27 mmol/L , or 10.3 mg/dL ( P = 0.052 ) , and by 0.29 mmol/L , or 11.2 mg/dL ( P < 0.02 ) , respectively . Changes in lipids did not differ significantly by race or baseline lipid concentrations , except for HDL , which decreased more in participants with higher baseline HDL-cholesterol concentrations than in those with lower baseline HDL-cholesterol concentrations . The fruit and vegetable diet produced few significant lipid changes . CONCLUSIONS The DASH diet is likely to reduce coronary heart disease risk . The possible opposing effect on coronary heart disease risk of HDL reduction needs further study Objectives To estimate 10 year decline in cognitive function from longitudinal data in a middle aged cohort and to examine whether age cohorts can be compared with cross sectional data to infer the effect of age on cognitive decline . Design Prospect i ve cohort study . At study inception in 1985 - 8 , there were 10 308 participants , representing a recruitment rate of 73 % . Setting Civil service departments in London , United Kingdom . Participants 5198 men and 2192 women , aged 45 - 70 at the beginning of cognitive testing in 1997 - 9 . Main outcome measure Tests of memory , reasoning , vocabulary , and phonemic and semantic fluency , assessed three times over 10 years . Results All cognitive scores , except vocabulary , declined in all five age categories ( age 45 - 49 , 50 - 54 , 55 - 59 , 60 - 64 , and 65 - 70 at baseline ) , with evidence of faster decline in older people . In men , the 10 year decline , shown as change/range of test × 100 , in reasoning was −3.6 % ( 95 % confidence interval −4.1 % to −3.0 % ) in those aged 45 - 49 at baseline and −9.6 % ( −10.6 % to −8.6 % ) in those aged 65 - 70 . In women , the corresponding decline was −3.6 % ( −4.6 % to −2.7 % ) and −7.4 % ( −9.1 % to −5.7 % ) . Comparisons of longitudinal and cross sectional effects of age suggest that the latter overestimate decline in women because of cohort differences in education . For example , in women aged 45 - 49 the longitudinal analysis showed reasoning to have declined by −3.6 % ( −4.5 % to −2.8 % ) but the cross sectional effects suggested a decline of −11.4 % ( −14.0 % to −8.9 % ) . Conclusions Cognitive decline is already evident in middle age ( age 45 - 49 ) Depressive symptoms may increase the risk of progressing from mild cognitive impairment ( MCI ) to dementia . Consumption of n-3 PUFA may alleviate both cognitive decline and depression . The aim of the present study was to investigate the benefits of supplementing a diet with n-3 PUFA , DHA and EPA , for depressive symptoms , quality of life ( QOL ) and cognition in elderly people with MCI . We conducted a 6-month double-blind , r and omised controlled trial . A total of fifty people aged > 65 years with MCI were allocated to receive a supplement rich in EPA ( 1·67 g EPA + 0·16 g DHA/d ; n 17 ) , DHA ( 1·55 g DHA + 0·40 g EPA/d ; n 18 ) or the n-6 PUFA linoleic acid ( LA ; 2·2 g/d ; n 15 ) . Treatment allocation was by minimisation based on age , sex and depressive symptoms ( Geriatric Depression Scale , GDS ) . Physiological and cognitive assessment s , question naires and fatty acid composition of erythrocytes were obtained at baseline and 6 months ( completers : n 40 ; EPA n 13 , DHA n 16 , LA n 11 ) . Compared with the LA group , GDS scores improved in the EPA ( P=0·04 ) and DHA ( P=0·01 ) groups and verbal fluency ( Initial Letter Fluency ) in the DHA group ( P=0·04 ) . Improved GDS scores were correlated with increased DHA plus EPA ( r 0·39 , P=0·02 ) . Improved self-reported physical health was associated with increased DHA . There were no treatment effects on other cognitive or QOL parameters . Increased intakes of DHA and EPA benefited mental health in older people with MCI . Increasing n-3 PUFA intakes may reduce depressive symptoms and the risk of progressing to dementia . This needs to be investigated in larger , depressed sample s with MCI BACKGROUND Docosahexaenoic acid ( DHA ) is important for brain function , and its status is dependent on dietary intakes . Therefore , individuals who consume diets low in omega-3 ( n-3 ) polyunsaturated fatty acids may cognitively benefit from DHA supplementation . Sex and apolipoprotein E genotype ( APOE ) affect cognition and may modulate the response to DHA supplementation . OBJECTIVES We investigated whether a DHA supplement improves cognitive performance in healthy young adults and whether sex and APOE modulate the response . DESIGN Healthy adults ( n = 176 ; age range : 18 - 45 y ; nonsmoking and with a low intake of DHA ) completed a 6-mo r and omized , placebo-controlled , double-blind intervention in which they consumed 1.16 g DHA/d or a placebo . Cognitive performance was assessed by using a computerized cognitive test battery . For all tests , z scores were calculated and clustered into cognitive domains as follows : episodic and working memory , attention , reaction time ( RT ) of episodic and working memory , and attention and processing speed . ANCOVA was conducted with sex and APOE as independent variables . RESULTS RTs of episodic and working memory improved with DHA compared with placebo [ mean difference ( 95 % CI ) : -0.18 SD ( -0.33 , -0.03 SD ) ( P = 0.02 ) and -0.36 SD ( -0.58 , -0.14 SD ) ( P = 0.002 ) , respectively ] . Sex × treatment interactions occurred for episodic memory ( P = 0.006 ) and the RT of working memory ( P = 0.03 ) . Compared with the placebo , DHA improved episodic memory in women [ 0.28 SD ( 0.08 , 0.48 SD ) ; P = 0.006 ] and RTs of working memory in men [ -0.60 SD ( -0.95 , -0.25 SD ) ; P = 0.001 ] . APOE did not affect cognitive function , but there were some indications of APOE × sex × treatment interactions . CONCLUSIONS DHA supplementation improved memory and the RT of memory in healthy , young adults whose habitual diets were low in DHA . The response was modulated by sex . This trial was registered at the New Zeal and Clinical Trials Registry ( http://www.anzctr.org.au/default.aspx ) as ACTRN12610000212055 Studies in rodents indicate that diets deficient in omega-3 polyunsaturated fatty acids ( n–3 PUFA ) lower dopamine neurotransmission as measured by striatal vesicular monoamine transporter type 2 ( VMAT2 ) density and amphetamine-induced dopamine release . This suggests that dietary supplementation with fish oil might increase VMAT2 availability , enhance dopamine storage and release , and improve dopamine-dependent cognitive functions such as working memory . To investigate this mechanism in humans , positron emission tomography ( PET ) was used to measure VMAT2 availability pre- and post-supplementation of n–3 PUFA in healthy individuals . Healthy young adult subjects were scanned with PET using [11C]-(+)-α-dihydrotetrabenzine ( DTBZ ) before and after six months of n–3 PUFA supplementation ( Lovaza , 2 g/day containing docosahexaenonic acid , DHA 750 mg/d and eicosapentaenoic acid , EPA 930 mg/d ) . In addition , subjects underwent a working memory task ( n-back ) and red blood cell membrane ( RBC ) fatty acid composition analysis pre- and post-supplementation . RBC analysis showed a significant increase in both DHA and EPA post-supplementation . In contrast , no significant change in [11C]DTBZ binding potential ( BPND ) in striatum and its subdivisions were observed after supplementation with n–3 PUFA . No correlation was evident between n–3 PUFA induced change in RBC DHA or EPA levels and change in [11C]DTBZ BPND in striatal subdivisions . However , pre-supplementation RBC DHA levels was predictive of baseline performance ( i.e. , adjusted hit rate , AHR on 3-back ) on the n-back task ( y = 0.19 + 0.07 , r2 = 0.55 , p = 0.009 ) . In addition , subjects AHR performance improved on 3-back post-supplementation ( pre 0.65±0.27 , post 0.80±0.15 , p = 0.04 ) . The correlation between n-back performance , and DHA levels are consistent with reports in which higher DHA levels is related to improved cognitive performance . However , the lack of change in [11C]DBTZ BPND indicates that striatal VMAT2 regulation is not the mechanism of action by which n–3 PUFA improves cognitive performance Abstract . The effects of capsules containing 60 mg of a st and ardised extract of Ginkgo biloba ( GK501 ) and 100 mg of a st and ardised extract of Panax ginseng ( G115 ) on various aspects of cognitive function were assessed in healthy middle-aged volunteers . A double blind , placebo controlled , 14 week , parallel group , repeated assessment , multi-centre trial of two dosing regimens , 160 mg b.i.d . and 320 mg o.d . was conducted . Two hundred and fifty-six healthy middle-aged volunteers successfully completed the study . On various study days ( weeks 0 , 4 , 8 , 12 and 14 ) the volunteers performed a selection of tests of attention and memory from the Cognitive Drug Research computerised cognitive assessment system prior to morning dosing and again , at 1 , 3 and 6 h later . The volunteers also completed question naires about mood states , quality of life and sleep quality . The Ginkgo/ginseng combination was found significantly to improve an Index of Memory Quality , supporting a previous finding with the compound . This effect represented an average improvement of 7.5 % and reflected improvements to a number of different aspects of memory , including working and long-term memory . This enhancement to memory was seen throughout the 12-week dosing period and also after a 2-week washout . This represents the first substantial demonstration of improvements to the memory of healthy middle-aged volunteers produced by a phytopharmaceutical The omega-3 fatty acid docosahexaenoic acid ( DHA ) is essential for nervous system and retinal development and there is evidence to suggest that DHA deficiencies increase with normal aging . A triple-blind placebo-controlled r and omized repeated- measures trial was conducted with 74 healthy participants , aged 45 - 77 years . Cognitive and visual acuity measures and plasma levels of DHA were determined at baseline and after 90 days of administration of either HiDHA ( ® ) ( Clover Corp. , Sydney , NSW , Australia : 1000 mg of tuna oil ; comprising 252 mg DHA , 60 mg EPA and 10 mg vitamin E ) or placebo ( 1000 mg soybean oil ) . Ninety days of DHA supplementation was found to significantly raise both plasma DHA and total ω-3 plasma levels in the treatment group , as well as significantly lower total ω-6 levels . However , no significant effects of DHA supplementation on cognitive functioning were found . For participants with corrected vision , the group receiving DHA were found to have significantly better right eye visual acuity posttreatment in comparison with the placebo group ( F(1,22 ) = 7.651 ; p = 0.011 ; partial η(2 ) = 0.258 ) Abstract Age-related changes in nutritional status can play an important role in brain functioning . Specific nutrient deficiencies in the elderly may exacerbate pathological processes in the brain . Consequently , the potential of nutritional intervention to prevent or delay cognitive impairment and the development of dementia is an important topic . A r and omized , double-blind , placebo-controlled trial has been performed in 25 elderly subjects ( 86 ± 6 years , 20 females , 5 males ) with mild cognitive impairment ( MCI ) . These subjects were r and omly assigned to supplement their diet with either an oily emulsion of docosahexaenoic acid (DHA)-phospholipids containing melatonin and tryptophan ( 11 subjects ) or a placebo ( 14-matched subjects ) for 12 weeks . The main aim of this study was to evaluate the efficacy of the dietary supplement on cognition , by the assessment at the start and after 12 weeks of : ( 1 ) Orientation and other cognitive functions : Mini-Mental State Examination ( MMSE ) ; ( 2 ) Short-term memory : digit , verbal , and spatial span ( digit span ; verbal span ; Corsi 's test ) ; ( 3 ) Long-term memory : Rey 's auditory-verbal learning test ; ‘ short story ’ test ; Rey-Osterrieth complex figure ( recall ) ; ( 4 ) Attentional abilities : attentive matrices ; ( 5 ) Executive functions : Weigl 's sorting test ; phonological fluency ‘ FAS ’ ; ( 6 ) Visuo-constructional and visuo-spatial abilities : copy of simple drawings ; Rey-Osterrieth complex figure ( copy ) ; ( 7 ) Language : semantic fluency ; ( 8) Mood : Geriatric Depression Scale ( GDS ) . Moreover , Sniffin ' Sticks olfaction test and Mini Nutritional Assessment ( MNA ) have been performed . After 12 weeks , a significant treatment effect for the MMSE ( P < 0.001 ) and a positive trend for the semantic verbal fluency was found in the supplement group ( P < 0.06 ) . A significant treatment effect was found out for the olfactory sensitivity assessment ( P < 0.009 ) . As regards the nutrition evaluation , after 12 weeks of treatment the supplemented group showed an improvement in the MNA score with a significant difference relative to placebo ( P < 0.005 ) . Older adults with MCI had significant improvements in several measures of cognitive function when supplemented with an oily emulsion of DHA-phospholipids containing melatonin and tryptophan for 12 weeks , compared with the placebo |
13,553 | 26,419,206 | Subanalyses showed that PE were associated with self-harm , suicidal ideation as well as suicidal attempts .
All studies had scope for considerable residual confounding ; effect sizes adjusted for depression were significantly smaller than effect sizes unadjusted for depression .
PE are associated with self-injurious behaviour , suggesting they have potential as passive markers of suicidality .
Given evidence that PE represent an indicator of severity of non-psychotic psychopathology , the association between PE and self-injurious behaviour probably reflects a greater likelihood of self-injurious behaviour in more severe states of mental distress | BACKGROUND Recent studies suggest that psychotic experiences ( PE ) in the general population are associated with an increased risk of self-injurious behaviour .
Both the magnitude of this association and the level of adjustment for confounders vary among studies . | Purpose Whilst psychotic experiences are associated with suicidal behaviour in a number of studies the value of psychotic experiences for the prediction of suicidal behaviour and the role of depressive symptoms in this relationship is not clear . We examined the association between psychotic experiences and subsequent suicidal behaviour and examine the role of depressive symptoms in this relationship . Methods Psychotic experiences and depressive symptoms at age 12 and 16 years , and suicidal behaviour at age 16 years were assessed in participants ( prospect i ve analysis n = 3171 ; cross-sectional analysis n = 3952 ) from a population -based cohort . Results Psychotic experiences ( OR 1.75 95 % CI 1.20 , 2.54 ) and depression ( OR 3.97 95 % CI 2.56 , 6.15 ) at 12 years were independently associated with suicidal behaviour at 16 years after adjustment for confounding . There was no evidence that the relationship between psychotic experiences and suicidal behaviour was stronger in participants who were also depressive . A ROC analysis showed that adding information on psychotic experiences to measures of depressive symptoms had hardly any effect on improving prediction of suicidal behaviour ( AUC increased from 0.64 to 0.65 ) . Whereas adding a measure of depressive symptoms to the measure of psychotic experiences improved prediction substantially ( AUC 0.56–0.65 ) . Conclusions Psychotic experiences and depression are independently associated with suicidal behaviour although the association with depression is substantially stronger . Psychotic experiences alone are not a strong predictor of later suicidal behaviour and add little to predicting the risk of suicidal behaviour over and above the information provided by depressive symptoms Little is known about the occurrence and predictors of the psychosis spectrum in large non- clinical community sample s of U.S. youths . We aim ed to bridge this gap through assessment of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort , a collaborative investigation of clinical and neurobehavioral phenotypes in a prospect ively accrued cohort of youths , funded by the National Institute of Mental Health . Youths ( age 11 - 21 ; N=7,054 ) and collateral informants ( caregiver/legal guardian ) were recruited through the Children 's Hospital of Philadelphia and administered structured screens of psychosis spectrum symptoms , other major psychopathology domains , and substance use . Youths were also administered a computerized neurocognitive battery assessing five neurobehavioral domains . Predictors of psychosis spectrum status in physically healthy participants ( N=4,848 ) were examined using logistic regression . Among medically healthy youths , 3.7 % reported threshold psychotic symptoms ( delusions and /or hallucinations ) . An additional 12.3 % reported significant sub-psychotic positive symptoms , with odd/unusual thoughts and auditory perceptions , followed by reality confusion , being the most discriminating and widely endorsed attenuated symptoms . A minority of youths ( 2.3 % ) endorsed sub clinical negative/disorganized symptoms in the absence of positive symptoms . Caregivers reported lower symptom levels than their children . Male gender , younger age , and non-European American ethnicity were significant predictors of spectrum status . Youths with spectrum symptoms had reduced accuracy across neurocognitive domains , reduced global functioning , and increased odds of depression , anxiety , behavioral disorders , substance use and suicidal ideation . These findings have public health relevance for prevention and early intervention IMPORTANCE Up to 1 million persons die by suicide annually . However , a lack of risk markers makes suicide risk assessment one of the most difficult areas of clinical practice . OBJECTIVE To assess psychotic symptoms ( attenuated or frank ) as a clinical marker of risk for suicide attempt . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 1112 school-based adolescents ( aged 13 - 16 years ) , assessed at baseline and at 3 and 12 months for self-reported psychopathology , psychotic symptoms , and suicide attempts . MAIN OUTCOMES AND MEASURES Suicide attempts at the 3- and 12-month follow-up and acute suicide attempts ( defined as those occurring in the 2 weeks before an assessment ) . RESULTS Of the total sample , 7 % reported psychotic symptoms at baseline . Of that sub sample , 7 % reported a suicide attempt by the 3-month follow-up compared with 1 % of the rest of the sample ( odds ratio [ OR ] , 10.01 ; 95 % CI , 2.24 - 45.49 ) , and 20 % reported a suicide attempt by the 12-month follow-up compared with 2.5 % of the rest of the sample ( OR , 11.27 ; 95 % CI , 4.44 - 28.62 ) . Among adolescents with baseline psychopathology who reported psychotic symptoms , 14 % reported a suicide attempt by 3 months ( OR , 17.91 ; 95 % CI , 3.61 - 88.82 ) and 34 % reported a suicide attempt by 12 months ( OR , 32.67 ; 95 % CI , 10.42 - 102.41 ) . Adolescents with psychopathology who reported psychotic symptoms had a nearly 70-fold increased odds of acute suicide attempts ( OR , 67.50 ; 95 % CI , 11.41 - 399.21 ) . Differences were not explained by nonpsychotic psychiatric symptom burden , multimorbidity , or substance use . In a causative model , the population -attributable fraction of suicide attempts would be 56 % to 75 % for psychotic symptoms . CONCLUSIONS AND RELEVANCE Adolescents with psychopathology who report psychotic symptoms are at clinical high risk for suicide attempts . More careful clinical assessment of psychotic symptoms ( attenuated or frank ) in mental health services and better underst and ing of their pathological significance are urgently needed BACKGROUND Non-suicidal self-injury ( NSSI ) is the deliberate and direct injuring of body tissue without suicidal intent for purpose s not socially sanctioned . Few studies have examined the correlates of NSSI among young adults . This study aim ed to identify predictors of lifetime and past-year NSSI , and describe motives for NSSI and disclosure of NSSI to others . METHOD Interviews were conducted annually with 1081 students enrolled in the College Life Study , a prospect i ve longitudinal study conducted at a large public mid-Atlantic university . NSSI characteristics were assessed at Year 4 . Demographic and predictor variables were assessed during Years 1 to 4 . Multivariate logistic regression models were used to identify correlates of lifetime NSSI and predictors of past-year NSSI . RESULTS The prevalence of past-year and lifetime NSSI was 2 % and 7 % respectively ( > 70 % were female for both lifetime and past-year NSSI ) . Seven percent of NSSI cases self-injured once , whereas almost half self-injured six or more times . Independent predictors of past-year NSSI were maternal depression , non-heterosexual orientation , affective dysregulation and depression . Independent predictors of lifetime NSSI were depression , non-heterosexual orientation , paternal depression and female sex . One in six participants with NSSI had attempted suicide by young adulthood . The three most commonly reported motives for NSSI were mental distress , coping and situational stressors . Most ( 89 % ) told someone about their NSSI , most commonly a friend ( 68 % ) . CONCLUSIONS This study identified unique predictors of NSSI , which should help to eluci date its etiology and has implication s for early identification and interventions CONTEXT It has been reported that childhood psychotic symptoms are common in the general population and may signal neurodevelopmental processes that lead to schizophrenia . However , it is not clear whether these symptoms are associated with the same extensive risk factors established for adult schizophrenia . OBJECTIVE To examine the construct validity of children 's self-reported psychotic symptoms by testing whether these symptoms share the risk factors and clinical features of adult schizophrenia . DESIGN Prospect i ve , longitudinal cohort study of a nationally representative birth cohort in Great Britain . PARTICIPANTS A total of 2232 twelve-year-old children followed up since age 5 years ( retention , 96 % ) . Main Outcome Measure Children 's self-reported hallucinations and delusions . RESULTS Children 's psychotic symptoms are familial and heritable and are associated with social risk factors ( eg , urbanicity ) ; cognitive impairments at age 5 ; home-rearing risk factors ( eg , maternal expressed emotion ) ; behavioral , emotional , and educational problems at age 5 ; and comorbid conditions , including self-harm . CONCLUSIONS The results provide a comprehensive picture of the construct validity of children 's self-reported psychotic symptoms . For research ers , the findings indicate that children who have psychotic symptoms can be recruited for neuroscience research to determine the pathogenesis of schizophrenia . For clinicians , the findings indicate that psychotic symptoms in childhood are often a marker of an impaired developmental process and should be actively assessed BACKGROUND Childhood psychotic symptoms have been used as a sub clinical phenotype of schizophrenia in etiological research and as a target for preventative interventions . However , recent studies have cast doubt on the specificity of these symptoms for schizophrenia , suggesting alternative outcomes such as anxiety and depression . Using a prospect i ve longitudinal birth cohort we investigated whether childhood psychotic symptoms predicted a diagnosis of schizophrenia or other psychiatric disorders by 38 years of age . METHOD Participants were drawn from a birth cohort of 1037 children from Dunedin , New Zeal and , who were followed prospect ively to 38 years of age ( 96 % retention rate ) . Structured clinical interviews were administered at age 11 to assess psychotic symptoms and study members underwent psychiatric assessment s at ages 18 , 21 , 26 , 32 and 38 to obtain past-year DSM-III-R/IV diagnoses and self-reports of attempted suicides since adolescence . RESULTS Psychotic symptoms at age 11 predicted elevated rates of research diagnoses of schizophrenia and posttraumatic stress disorder ( PTSD ) and also suicide attempts by age 38 , even when controlling for gender , social class and childhood psychopathology . No significant associations were found for persistent anxiety , persistent depression , mania or persistent substance dependence . Very few of the children presenting with age-11 psychotic symptoms were free from disorder by age 38 . CONCLUSIONS Childhood psychotic symptoms were not specific to a diagnosis of schizophrenia in adulthood and thus future studies of early symptoms should be cautious in extrapolating findings only to this clinical disorder . However , these symptoms may be useful as a marker of adult mental health problems more broadly CONTEXT It has been suggested that patients with major depressive disorder ( MDD ) who display pretreatment features suggestive of bipolar disorder or bipolar spectrum features might have poorer treatment outcomes . OBJECTIVE To assess the association between bipolar spectrum features and antidepressant treatment outcome in MDD . DESIGN Open treatment followed by sequential r and omized controlled trials . SETTING Primary and specialty psychiatric outpatient centers in the United States . PARTICIPANTS Male and female out patients aged 18 to 75 years with a DSM-IV diagnosis of nonpsychotic MDD who participated in the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) study . INTERVENTIONS Open treatment with citalopram followed by up to 3 sequential next-step treatments . MAIN OUTCOME MEASURES Number of treatment levels required to reach protocol -defined remission , as well as failure to return for the postbaseline visit , loss to follow-up , and psychiatric adverse events . For this secondary analysis , putative bipolar spectrum features , including items on the mania and psychosis subscales of the Psychiatric Diagnosis Screening Question naire , were examined for association with treatment outcomes . RESULTS Of the 4041 subjects who entered the study , 1198 ( 30.0 % ) endorsed at least 1 item on the psychosis scale and 1524 ( 38.1 % ) described at least 1 recent maniclike/hypomaniclike symptom . Irritability and psychoticlike symptoms at entry were significantly associated with poorer outcomes across up to 4 treatment levels , as were shorter episodes and some neurovegetative symptoms of depression . However , other indicators of bipolar diathesis including recent maniclike symptoms and family history of bipolar disorder as well as summary measures of bipolar spectrum features were not associated with treatment resistance . CONCLUSION Self-reported psychoticlike symptoms were common in a community sample of out patients with MDD and strongly associated with poorer outcomes . Overall , the data do not support the hypothesis that unrecognized bipolar spectrum illness contributes substantially to antidepressant treatment resistance |
13,554 | 28,267,205 | For the comparison of radiotherapy plus chemoembolisation versus chemoembolisation alone , the risk ratio for one-year all-cause mortality was 0.51 ( 95 % confidence interval ( CI ) 0.41 to 0.62 ; P < 0.001 ; 9 trials ; low- quality evidence ) ; for complete response rate was 2.14 ( 95 % CI 1.47 to 3.13 ; P < 0.001 ; 7 trials ; low- quality evidence ) ; and for overall response rate defined as complete response plus partial response was 1.58 ( 95 % CI 1.40 to 1.78 ; P < 0.001 ; 7 trials ; low- quality evidence ) , all in favour of combined treatment with external beam radiotherapy plus transarterial chemoembolisation and seemingly supported by our Trial Sequential Analysis .
Additionally , the combined treatment was associated with a higher risk of elevated total bilirubin and elevated alanine aminotransferase .
AUTHORS ' CONCLUSIONS We found very low- and low- quality evidence suggesting that combined external beam radiotherapy and chemoembolisation may be associated with lower mortality and increased complete and overall response rates , despite an increased toxicity as expressed by a higher rise of bilirubin and alanine aminotransferase . | BACKGROUND Hepatocellular carcinoma is the most common liver neoplasm , the sixth most common cancer worldwide , and the third most common cause of cancer mortality .
Moreover , its incidence has increased dramatically in the past decade .
While surgical resection and liver transplantation are the main curative treatments , only around 20 % of people with early hepatocellular carcinoma may benefit from these therapies .
Current treatment options for unresectable hepatocellular carcinoma include various ablative and transarterial therapies in addition to the drug sorafenib .
OBJECTIVES To assess the benefits and harms of external beam radiotherapy in the management of localised unresectable hepatocellular carcinoma . | In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials PURPOSE To evaluate the efficacy and safety of high-dose , hypofractionated proton beam therapy for hepatocellular carcinoma ( HCC ) and intrahepatic cholangiocarcinoma ( ICC ) . MATERIAL S AND METHODS In this single-arm , phase II , multi-institutional study , 92 patients with biopsy-confirmed HCC or ICC , determined to be unresectable by multidisciplinary review , with a Child-Turcotte-Pugh score ( CTP ) of A or B , ECOG performance status of 0 to 2 , no extrahepatic disease , and no prior radiation received 15 fractions of proton therapy to a maximum total dose of 67.5 Gy equivalent . Sample size was calculated to demonstrate > 80 % local control ( LC ) defined by Response Evaluation Criteria in Solid Tumors ( RECIST ) 1.0 criteria at 2 years for HCC patients , with the parallel goal of obtaining acceptable precision for estimating outcomes for ICC . RESULTS Eighty-three patients were evaluable : 44 with HCC , 37 with ICC , and two with mixed HCC/ICC . The CTP score was A for 79.5 % of patients and B for 15.7 % ; 4.8 % of patients had no cirrhosis . Prior treatment had been given to 31.8 % of HCC patients and 61.5 % of ICC patients . The median maximum dimension was 5.0 cm ( range , 1.9 to 12.0 cm ) for HCC patients and 6.0 cm ( range , 2.2 to 10.9 cm ) for ICC patients . Multiple tumors were present in 27.3 % of HCC patients and in 12.8 % of ICC patients . Tumor vascular thrombosis was present in 29.5 % of HCC patients and in 28.2 % of ICC patients . The median dose delivered to both HCC and ICC patients was 58.0 Gy . With a median follow-up among survivors of 19.5 months , the LC rate at 2 years was 94.8 % for HCC and 94.1 % for ICC . The overall survival rate at 2 years was 63.2 % for HCC and 46.5 % ICC . CONCLUSION High-dose hypofractionated proton therapy demonstrated high LC rates for HCC and ICC safely , supporting ongoing phase III trials of radiation in HCC and ICC Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . PURPOSE To describe results of a planned interim analysis of a prospect i ve , r and omized clinical trial developed to compare treatment outcomes among patients with newly diagnosed hepatocellular carcinoma ( HCC ) . METHODS AND MATERIAL S Eligible subjects had either clinical or pathologic diagnosis of HCC and met either Milan or San Francisco transplant criteria . Patients were r and omly assigned to transarterial chemoembolization ( TACE ) or to proton beam radiation therapy . Patients r and omized to TACE received at least 1 TACE with additional TACE for persistent disease . Proton beam radiation therapy was delivered to all areas of gross disease to a total dose of 70.2 Gy in 15 daily fractions over 3 weeks . The primary endpoint was progression-free survival , with secondary endpoints of overall survival , local tumor control , and treatment-related toxicities as represented by posttreatment days of hospitalization . RESULTS At the time of this analysis 69 subjects were available for analysis . Of these , 36 were r and omized to TACE and 33 to proton . Total days of hospitalization within 30 days of TACE/proton was 166 and 24 days , respectively ( P<.001 ) . Ten TACE and 12 proton patients underwent liver transplantation after treatment . Viable tumor identified in the explanted livers after TACE/proton averaged 2.4 and 0.9 cm , respectively . Pathologic complete response after TACE/proton was 10%/25 % ( P=.38 ) . The 2-year overall survival for all patients was 59 % , with no difference between treatment groups . Median survival time was 30 months ( 95 % confidence interval 20.7 - 39.3 months ) . There was a trend toward improved 2-year local tumor control ( 88 % vs 45 % , P=.06 ) and progression-free survival ( 48 % vs 31 % , P=.06 ) favoring the proton beam treatment group . CONCLUSIONS This interim analysis indicates similar overall survival rates for proton beam radiation therapy and TACE . There is a trend toward improved local tumor control and progression-free survival with proton beam . There are significantly fewer hospitalization days after proton treatment , which may indicate reduced toxicity with proton beam therapy 4024 Background : Proton beam radiotherapy ( PRT ) has an excellent depth-dose profile that can deliver high dose to the liver tumor without debilitating liver function compared to photon beam radiotherapy . It is reasonable to evaluate the safety and efficacy of PRT prospect ively for hepatocellular carcinoma ( HCC ) . METHODS Eligibility criteria for this study were : solitary HCC ; neither surgery nor local ablation therapy were indicated ; no ascites ; age ≥20 years ; Zubord performance status is 0∼2 ; no serious co-morbidities other than liver cirrhosis ; written informed consent . Tumor close to the stomach or intestinal loop was not considered as a subject for this study . Clinical target volume ( CTV ) was defined as gross tumor volume plus 5 mm of lateral and cranio-caudal margin . PRT administering 76 GyE/20 fractions/5 weeks to the CTV was done using respiration-gated irradiation system ( ReGIS ) with 150∼190 MeV proton beam . Relative biological effectiveness of our proton beam was defined as 1.1 . No patients received transarterial chemoembolization or local ablation in combination with PRT . RESULTS Thirty patients were enrolled between May 1999 and Feb. 2003 . There were 20 male and 10 female with a median age of 70 years ( range : 48∼87 years ) . Maximum tumor diameter ranged from 25 ∼ 82 mm ( median 45 mm ) . All patients had liver cirrhosis of which the degree was Child class A in 9 , B in 19 , and C in 2 . Acute reactions of PRT were well tolerated , and PRT were completed as planned in all patients . After a median follow-up period of 31 months ( 14∼54 months ) , only 1 patient experienced tumor recurrence within the CTV and 2-year actuarial local control rate was as 96 % ( 95 % confidence interval : 88%∼100 % ) . Actuarial overall survival rate at 2 years was 64 % ( 46∼83 % ) . Pretreatment liver function that was evaluated with indocyanin green clearance at 15 minutes ( ICG 15 ) , and liver volume that received 30 GyE or more ( V30 ) significantly correlated with overall survival . CONCLUSIONS Since PRT showed minimal acute toxicity and excellent tumor control within CTV , it is expected as one of the convincing non-surgical treatment options for HCC . ICG 15 and V30 were considered as useful indicators of patient prognosis . No significant financial relationships to disclose 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 The purpose of this study was to evaluate the clinical efficacy , toxicity and adverse effects of stereotactic body radiotherapy ( SBRT ) combined with transarterial chemoembolization ( TACE ) in patients with advanced hepatocellular carcinoma ( HCC ) with portal vein tumor thrombosis ( PVTT ) . A total of 101 patients diagnosed with primary HCC with PVTT were enrolled in this study and were r and omly divided into three groups as follows : group A , 34 patients treated with γ-SBRT followed by TACE ; group B , 37 patients treated with TACE followed by γ-SBRT ; and group C , 30 patients treated with γ-SBRT alone . The effective response rate for the entire patient sample was 87.1 % ( 88/101 ) following a 3-month treatment . The differences in the response rate , survival rate , α-fetoprotein level restoration rate and rate of improvement of abdominal distention and discomfort between groups A and B were not statistically significant ( P>0.05 ) . However , the rates of groups A and B were higher compared to those of group C ( P<0.05 ) . The exacerbation rate of liver function in group A was lower compared to that in group B ( P<0.05 ) , although it exhibited no statistically significant difference from that in group C ( P>0.05 ) . No severe radiation-related complications were reported during the follow-up period . The combination of γ-SBRT and TACE was shown to be a relatively effective local treatment for primary HCC patients with PVTT . Compared to γ-SBRT followed by TACE and γ-SBRT alone , TACE followed by γ-SBRT may exert a negative effect on liver function . These results suggested that the combination of TACE and γ-SBRT may be considered a relatively effective , safe and feasible treatment method for primary HCC patients with PVTT , although TACE followed by γ-SBRT may negatively affect liver function Proton beam therapy ( PBT ) may provide useful local‐regional treatment for hepatocellular carcinoma ( HCC ) . The purpose of this study was to evaluate the safety and efficacy of PBT for HCC In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted The purpose of this study was to evaluate treatment-related toxicity , outcome , patterns of failure , and prognostic factors for patients with stage III unresectable hepatocellular carcinoma ( HCC ) treated with a combination of local 3-dimensional conformal radiotherapy ( 3D-CRT ) and transcatheter arterial chemoembolization ( TACE ) under the support of G-CSF . From October 1997 to August 2001 , 45 patients with stage III unresectable hepatocellular carcinoma underwent transcatheter arterial chemoembolization with local 3D-CRT . Twenty-seven patients were classified as having stage IIIA disease according to the American Joint Committee on Cancer ( AJCC ) staging system and 18 were classified as stage IIIB . The mean diameter of the treated hepatic tumor was 8.5 cm . Before 3D-CRT , 2 cycles of transcatheter arterial chemoembolization were prescribed . Forty-eight hours later , the G-CSF was prescribed for 5 days after the completion of every TACE . With the interval of 10 to 14 days after the second cycle of TACE , 3D-CRT was prescribed to all patients with a total dose of 50.4 Gy at 1.8 Gy per fraction 5 days per week . After the completion of 3D-CRT , the additional 2 cycles of TACE were given . All patients were monitored for treatment-related toxicity , outcome , patterns of failure , causes of death , and prognostic factors . Forty-two of 45 patients were treated smoothly with the primary schedule . In a median follow-up period of 27 months , 22 patients were alive and 23 were dead . Progressive disease occurred in 28 patients , including local recurrence alone ( 4 patients ) , distant metastases with local recurrence ( 8 patients ) , and distant metastases alone ( 16 patients ) . Nine patients developed radiation-induced liver disease ( RILD ) . Three patients had treatment-related gastrointestinal bleeding . There were 2 treatment-related deaths , including 1 from RILD and 1 from gastrointestinal bleeding . Complete regression ( CR ) was observed in 6 patients , partial regression ( PR ) in 35 patients , and stable disease ( SD ) in 4 patients . The median overall survival duration from treatment was 23.5 months with a 1-year overall survival rate of 68.5 % , a 2-year survival rate of 48.3 % , and a 3-year survival rate of 22.6 % . The median freedom from progressive disease survival duration from treatment was 25 months with 1-year , 2-year , and 3-year progression-free survival rates of 76.2 % , 56.8 % , and 42.4 % , respectively . The stage of HCC , regional lymph node status , portal vein thrombosis , pretreatment & agr;-fetoprotein level ( AFP ) , and tumor size affected the treatment outcomes significantly . Therefore , for patients with stage III unresectable hepatocellular carcinoma , combined local 3D conformal radiotherapy with transcatheter arterial chemoembolization under the support of G-CSF is an effective treatment protocol . Further research is required to decrease distant metastases and to determine the safe irradiation dose-volume This paper is an overview of the new response evaluation criteria in solid tumours : revised RECIST guideline ( version 1 . 1 ) , with a focus on up date d contents OBJECTIVE We evaluated the inter-rater reliability ( IRR ) of assessing the quality of evidence ( QoE ) using the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) approach . STUDY DESIGN AND SETTING On completing two training exercises , participants worked independently as individual raters to assess the QoE of 16 outcomes . After recording their initial impression using a global rating , raters grade d the QoE following the GRADE approach . Subsequently , r and omly paired raters su bmi tted a consensus rating . RESULTS The IRR without using the GRADE approach for two individual raters was 0.31 ( 95 % confidence interval [ 95 % CI ] = 0.21 - 0.42 ) among Health Research Methodology students ( n = 10 ) and 0.27 ( 95 % CI = 0.19 - 0.37 ) among the GRADE working group members ( n = 15 ) . The corresponding IRR of the GRADE approach in assessing the QoE was significantly higher , that is , 0.66 ( 95 % CI = 0.56 - 0.75 ) and 0.72 ( 95 % CI = 0.61 - 0.79 ) , respectively . The IRR further increased for three ( 0.80 [ 95 % CI = 0.73 - 0.86 ] and 0.74 [ 95 % CI = 0.65 - 0.81 ] ) or four raters ( 0.84 [ 95 % CI = 0.78 - 0.89 ] and 0.79 [ 95 % CI = 0.71 - 0.85 ] ) . The IRR did not improve when QoE was assessed through a consensus rating . CONCLUSION Our findings suggest that trained individuals using the GRADE approach improves reliability in comparison to intuitive judgments about the QoE and that two individual raters can reliably assess the QoE using the GRADE system PURPOSE A phase II trial was conducted to determine if high-dose radiation with concurrent hepatic arterial floxuridine would improve survival in patients with unresectable intrahepatic malignancies . PATIENTS AND METHODS Three-dimensional conformal high-dose radiation therapy was delivered concurrently with hepatic arterial floxuridine in 128 patients . The radiation dose was based on a normal-tissue complication probability model and subjected the patient to an estimated maximum risk of radiation-induced liver disease of 10 % to 15 % . The study design provided more than 80 % power to detect a two-fold increase in median survival compared with historical controls at a 5 % significance level . RESULTS The median radiation dose delivered was 60.75 Gy ( 1.5-Gy fractions bid ) . At a median follow-up time of 16 months ( 26 months in patients who were alive ) the median survival was 15.8 months ( 95 % CI , 12.6 to 18.3 months ) , significantly longer than in the historical control . The actuarial 3-year survival was 17 % . The total dose was the only significant predictor of survival . Primary hepatobiliary tumors had a significantly greater tendency to remain confined to the liver than did colorectal cancer metastases . Overall toxicity was acceptable , with 27 patients ( 21 % ) and 11 patients ( 9 % ) developing grade 3 and 4 toxicity , respectively , and one treatment-related death . CONCLUSION The results suggest that , compared with historical controls , high-dose focal liver irradiation with hepatic artery floxuridine prolongs survival in patients with unresectable chemotherapy-refractory metastatic colorectal cancer and primary hepatobiliary tumors . This provides a rationale for intensification of local therapy for unresectable hepatobiliary cancers and integration of this regimen with newer systemic therapy for patients with colorectal cancer PURPOSE To describe outcomes of prospect i ve trials of stereotactic body radiotherapy ( SBRT ) for hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS Two trials of SBRT for patients with active HCC unsuitable for st and ard locoregional therapies were conducted from 2004 to 2010 . All patients had Child-Turcotte-Pugh class A disease , with at least 700 mL of non-HCC liver . The SBRT dose range was 24 to 54 Gy in six fractions . Primary end points were toxicity and local control at 1 year ( LC1y ) , defined as no progressive disease ( PD ) of irradiated HCC by RECIST ( Response Evaluation Criteria in Solid Tumors ) . RESULTS A total of 102 patients were evaluable ( Trial 1 , 2004 to 2007 : n = 50 ; Trial 2 , 2007 to 2010 : n = 52 ) . Underlying liver disease was hepatitis B in 38 % of patients , hepatitis C in 38 % , alcohol related in 25 % , other in 14 % , and none in 7 % . Fifty-two percent received prior therapies ( no prior sorafenib ) . TNM stage was III in 66 % , and 61 % had multiple lesions . Median gross tumor volume was 117.0 mL ( range , 1.3 to 1,913.4 mL ) . Tumor vascular thrombosis ( TVT ) was present in 55 % , and extrahepatic disease was present in 12 % . LC1y was 87 % ( 95 % CI , 78 % to 93 % ) . SBRT dose ( hazard ratio [ HR ] = 0.96 ; P = .02 ) and being in Trial 2 ( HR = 0.38 ; P = .03 ) were associated with LC1y on univariate analysis . Toxicity ≥ grade 3 was seen in 30 % of patients . In seven patients ( two with TVT PD ) , death was possibly related to treatment ( 1.1 to 7.7 months after SBRT ) . Median overall survival was 17.0 months ( 95 % CI , 10.4 to 21.3 months ) , for which only TVT ( HR = 2.47 ; P = .01 ) and being in Trial 2 ( HR = 0.49 ; P = .01 ) were significant on multivariate analysis . CONCLUSION These results provide strong rationale for study ing SBRT for HCC in a r and omized trial |
13,555 | 30,539,404 | Concluding , it was not possible to state that repeated applications of aPDT , in association with non-surgical treatment of residual pockets , have effective clinical effects in the periodontal maintenance therapy . | The aim of this study was to assess the effects of repeated applications of antimicrobial photodynamic therapy ( aPDT ) on the non-surgical periodontal treatment of residual pockets . | Background : Photodynamic therapy ( PDT ) is a method of microbial reduction which can benefit periodontal treatment in areas of difficult access , such as deep pockets and furcations . The aim of this r and omized controlled clinical trial was to evaluate the effects of PDT as an adjunct to full-mouth ultrasonic debridement in the treatment of severe chronic periodontitis . Material and Methods : Twenty-two patients with at least one pocket with a probing depth ( PD ) of ≥7 mm and one pocket with a PD of ≥5 mm and bleeding on probing ( BOP ) on each side of the mouth were included , characterizing a split mouth design . The control group underwent full-mouth ultrasonic debridement and the test group received the same treatment associated with PDT . The PDT was performed on only one side of the mouth and the initial step consisted of subgingival irrigation with 0.005 % methylene blue dye . Two minutes after applying the photosensitizer , the low power laser - AsGaAl ( Photon Lase III - PL7336 , DMC , São Carlos -São Paulo , Brazil ) was applied ( 660 nm , 100 mW , 9 J , 90 seconds per site , 320 J/cm2 , diameter tip 600 µm).The following clinical parameters were evaluated : plaque index , gingival index , BOP , gingival recession ( GR ) , PD , and clinical attachment level ( CAL ) . All parameters were collected before , 1 , 3 and 6 months after treatment . Results : An improvement in BOP , PD and CAL was observed after treatment , in both groups , but without any difference between them . After 6 months , the PD decreased from 5.11±0.56 mm to 2.83±0.47 mm in the test group ( p<0.05 ) and from 5.15±0.46 mm to 2.83±0.40 mm in the control group ( p<0.05 ) . The CAL changed , after 6 months , from 5.49±0.76 mm to 3.41±0.84 mm in the test group ( p<0.05 ) and from 5.53±0.54 to 3.39±0.51 mm in the control group ( p<0.05 ) . Conclusion : Both approaches result ed in significant clinical improvements in the treatment of severe chronic periodontits , however , the PDT did not provide any additional benefit to those obtained with full-mouth ultrasonic debridement used alone AIM To evaluate the potential of antimicrobial photodynamic therapy ( aPDT ) as an adjunct to scaling and root planing ( SRP ) in the treatment of chronic periodontitis . MATERIAL AND METHODS In a single-centred r and omized and controlled clinical trial , 90 patients ( 51 females and 39 males ) with untreated chronic periodontitis were r and omly assigned to receive SRP with aPDT ( test group ) or SRP alone ( control group ) . Clinical parameters and halitosis were recorded for 6 months after treatment by a periodontist who was blinded to the procedure . RESULTS Inter-group and intra-group statistical analyses were performed . Significant difference between the two groups with respect to each variable was assessed using non-parametric Rank Order ancova . Probing pocket depth and clinical attachment levels showed statistically significant reduction in the test group on evaluation at 3 months and 6 months as compared to the control group ( p < 0.05 ) . A statistically significant improvement in gingival index and gingival bleeding index was seen for the test group after 2 weeks and 1 month of aPDT ( p < 0.01 ) , whereas the improvement in gingival index and gingival bleeding index at 3 months and in plaque index at 2 weeks after aPDT was less ( p < 0.05 ) . Also , a significant difference was detected for the test group at 1 month in terms of halitosis ( p < 0.05 ) , which did not persist for long . CONCLUSIONS Antimicrobial photodynamic therapy acts as a beneficial adjunct to SRP in non-surgical treatment and management of chronic periodontitis in short-term . Further studies are required to assess the long-term effectiveness of aPDT This study aims to assess in residual periodontal pockets the clinical , microbiological , and local biological effects of antimicrobial photodynamic therapy ( PDT ) , delivered after ultrasonic instrumentation either once or twice in a 1-week interval . A single center , three-arm r and omized longitudinal study was carried out for 6 months . Twenty-eight systemically healthy patients on periodontal maintenance with residual pockets ( pocket depth ( PD ) ≥5 mm , clinical attachment loss ≥2 mm , and bleeding upon probing ( BOP+ ) ) were included . Residual pockets on three teeth , separated from each other by at least two other teeth , served as study sites . After ultrasonic debridement , they were r and omly assigned to either PDT delivered twice within 1 week ( group A ) , PDT delivered only once ( group B ) , or sham treatment without activating the laser ( group C ) . Methylene blue was applied with a blunt irrigator tip into the pockets . Sites were irradiated with laser light at a wavelength of 670 nm using a light-diffusing tip introduced into the pocket . Initial PD was 5.9 ± 0.9 , 6.3 ± 1.3 , and 6.3 ± 1.5 mm in groups A , B , and C , respectively , differences being nonsignificant . PD was significantly reduced in all groups . At month 3 , PD was significantly lower in groups A ( 2.9 ± 1.1 mm ; p = 0.04 ) and B ( 2.8 ± 1.1 mm ; p = 0.03 ) compared to group C ( 3.5 ± 1.2 mm ) . At month 6 , none of the sites in group A had persisting pockets PD > 4 mm and BOP+ , whereas two sites in group B and four sites in group C stayed in this category . Detection frequencies of the studied microorganisms at > 1,000 and > 100.000 cells/ml did not change significantly from baseline to months 3 or 6 in any group . A significant overall decrease was observed from baseline to month 6 for C-reactive protein , serum amyloid A , fibrinogen , procalcitonin , and α-2 macroglobulin . When looking at the groups separately , C-reactive protein was significantly lower only if the laser had been activated twice ( p < 0.05 ) . Other differences between groups were not significant . A single or double episodes of PDT had some additional benefit over ultrasonic instrumentation alone AIM A r and omized controlled clinical trial was design ed to evaluate the efficacy of the photodynamic therapy ( PDT ) in the treatment of residual pockets of chronic periodontitis patients . MATERIAL AND METHODS Thirty-four patients with at least four residual periodontal pockets undergoing maintenance care were included and r and omly assigned to test group ( PDT , n = 18 ) or control group ( sham procedure , n = 16 ) . The intervention was performed at baseline , 3 , 6 and 12 months . Clinical parameters such as pocket probing depth ( PPD ) , clinical attachment level ( CAL ) , bleeding on probing ( BoP ) and plaque index ( PI ) were measured before intervention and after 3 , 6 and 12 months . Subgingival sample s were obtained at baseline , and after 7 days , 3 , 6 and 12 months to quantify Aggregatibacter actinomycetemcomitans , Porphyromonas gingivalis , Treponema denticola and Tannerella forsythia by real-time polimerase chain reaction ( PCR ) . RESULTS All clinical variables showed significant improvement during the study , but there was no significant difference between test and control groups . The microbiological analyses showed no differences between groups at any time during the study . CONCLUSION Within the limits of this clinical trial and considering the laser and photosensitizer protocol used , PDT failed to demonstrate additional clinical and bacteriological benefits in residual pockets treatment Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results BACKGROUND Single photodynamic therapy ( PDT ) has been effective in initial periodontal therapy , but only improved bleeding on probing ( BoP ) in maintenance patients after a single use . Repeated PDT has not been addressed . OBJECTIVES To study the possible added benefits of repeated adjunctive PDT to conventional treatment of residual pockets in patients enrolled in periodontal maintenance . MATERIAL AND METHODS Ten maintenance patients with 70 residual pockets [ probing pocket depth (PPD)>or=5 mm ] were r and omly assigned for treatment five times in 2 weeks ( Days 0 , 1 , 2 , 7 , 14 ) with PDT ( test ) or non-activated laser ( control ) following debridement . The primary outcome variable was PPD , and the secondary variables were clinical attachment level ( CAL ) and BoP. These were assessed at 3 , 6 and 12 months following the interventions . RESULTS Greater PPD reductions were observed in the test ( -0.67 + /- 0.34 ; p=0.01 ) compared with the control patients ( -0.04 + /- 0.33 ; NS ) after 6 months . Significant CAL gain ( + 0.52 + /- 0.31 ; p=0.01 ) was noted for the test , but not in the control ( -0.27 + /- 0.52 ; NS ) patients after 6 months . BoP percentages decreased significantly in test ( 97 - 64 % , 67 % , 77 % ) , but not control patients after 3 , 6 and 12 months . CONCLUSIONS Repeated ( five times ) PDT adjunctive to debridement yielded improved clinical outcomes in residual pockets in maintenance patients . The effects were best documented after 6 months BACKGROUND The study aims to compare the effects of adjunctive photodynamic therapy ( PDT ) with scaling and root debridement alone on periodontal parameters and inflammatory cytokines in residual pockets of patients undergoing maintenance therapy . METHODS 27 subjects , each with at least 2 residual pockets ≥5 mm , were recruited for this r and omized , split-mouth controlled trial , providing total of 72 sites . Probing pocket depth ( PPD ) , recession , clinical attachment loss ( CAL ) , plaque and bleeding on probing of all sites were examined at baseline , 3 and 6 months . Gingival crevicular fluids ( GCFs ) were collected to determine levels of IL-1β , IL-6 , IL-8 , TNF-α and MMP-8 via enzyme-linked immunosorbent assay . At baseline , all sites received subgingival instrumentation and polishing . In addition , test sites received a single application of PDT using Fotosan ® with toluidine blue O solution photosensitizer . At 3 and 6 months , site level analysis was performed for changes in clinical parameters and cytokine level . RESULTS Based on mixed model analysis , at 3 months , test sites showed significant reduction in CAL ( p=0.016 ) and PPD ( p=0.027 ) ( from 6.14±0.28 mm to 5.49±0.20 mm and 5.42±0.16 mm to 4.65±0.18 mm respectively ) compared to control sites ( from 6.32±0.24 mm to 6.08±0.17 mm and 5.32±0.13 mm to 5.15±0.15 mm respectively ) . At 6 months , these differences were no longer significant ( p=0.510 ) . Adjunctive PDT did not offer additional reduction in levels of GCF cytokines . CONCLUSIONS A single application of PDT to residual pockets provided a modest improvement of CAL and PPD over 3 months . Application of adjunctive PDT may lead to faster resolution of residual pockets and may be recommended for periodontal patients with slower healing capacity Experimental studies in animals and in vitro have shown the usefulness of photodynamic therapy ( PDT ) as an adjunct to periodontal treatment . The aim of this study was to evaluate the long-term clinical and microbiological effects of PDT associated with nonsurgical periodontal treatment . Three sites in each of 33 patients with chronic periodontitis were r and omly allocated in a split-mouth design to a treatment group : ( 1 ) scaling and root planing ( SRP group ) ; ( 2 ) SRP and irrigation with toluidine blue O ( TBO group ) ; and ( 3 ) SRP , irrigation with TBO and low-level laser irradiation ( PDT group ) . Clinical parameters including visible plaque index , bleeding gingival index , bleeding on probing , probing depth , gingival recession and clinical attachment level were measured at baseline , and after 60 , 90 and 180 days . Additionally , subgingival plaque sample s were collected for microbiological analysis by PCR . Intergroup and intragroup statistical analyses were performed . All treatment groups showed an improvement in all clinical parameters , and a significant reduction in the proportion of sites positive for periodontopathogens at 60 , 90 and 180 days compared to baseline ( p < 0.05 ) . None of the periodontal parameters showed a significant difference among the groups ( p > 0.05 ) . At 180 days , PDT treatment led to a significant reduction in the percentage of sites positive for all bacteria compared to SRP alone ( p < 0.05 ) . Within the limits of this study it may be concluded that PDT as an adjunct to periodontal treatment produced statistically significant reductions in some of the key periodontal pathogens but produced no statistically significant benefit in terms of clinical outcome AIM To test recolonization of periodontal lesions after full-mouth scaling and root planing ( FM-SRP ) or multiple session-SRP ( MS-SRP ) in a r and omized clinical trial and whether FM-SRP and MS-SRP result in different clinical outcomes . MATERIAL S AND METHODS Thirty-nine subjects were r and omly assigned to FM-SRP or MS-SRP groups . At baseline and after 3 months , probing pocket depth ( PPD ) , plaque index ( PlI ) and bleeding on probing ( BoP ) were recorded . At baseline , immediately after treatment , after 1 , 2 , 7 , 14 and 90 days , paper point sample s from a single site from the maxillary right quadrant were collected for microbiological analysis of five putative pathogens by polymerase chain reaction . RESULTS FM-SRP and MS-SRP result ed in significant reductions in PPD , BoP and PlI and the overall detection frequencies of the five species after 3 months without significant differences between treatments . Compared with MS-SRP , FM-SRP result ed in less recolonization of the five species , significantly for Treponema denticola , in the tested sites . CONCLUSION FM-SRP and MS-SRP result in overall clinical ly and microbiologically comparable outcomes where recolonization of periodontal lesions may be better prevented by FM-SRP Aims and Objectives : Harnessing Mother Nature 's bountiful remedies for rejuvenation has been in vogue since time immemorial . Turmeric contains the polyphenol Curcumin in its rhizome . It produces reactive oxygen species ( ROS ) with visible light irradiation as photodynamic therapy ( PDT ) - which vali date s its use in the treatment of periodontitis . This study compares Curcumin and Curcumin PDT as an adjunct to conventional Scaling and Root Planing ( SRP ) with SRP alone in the treatment of patients with chronic periodontitis . Material s and Methods : Sixty sites in fifteen untreated chronic periodontitis patients were r and omly assigned in a split mouth design for one of the treatment modalities ; 1 ) Scaling and root planing ( SRP ) alone , ( 2 ) SRP + Curcumin application for 5 min , ( 3 ) SRP + Curcumin application for 5 min + irradiation with blue light emitting diode of wavelength 470 nm for 5 min . ( Curcumin PDT ) on 0 day.(4 ) SRP + Curcumin PDT on “ 0 ” , 7th and 21st day . The clinical parameters included plaque index ( PI ) , bleeding on probing ( BOP ) measured by sulcus bleeding index ( SBI ) , probing pocket depth ( PPD ) , clinical attachment level ( CAL ) recorded at the baseline & 3rd month . The site with greatest probing pocket depth ( PPD ) was selected from each quadrant for bacterial sampling and culturing for Aggregatibacter actinomycetemcomitans ( Aa ) and other black pigment producing microorganisms ( BPB ) like Porphyromonas gingivalis & Prevotella intermedia . Conclusion : The present study showed that Curcumin photodynamic therapy is a valuable treatment modality adjunctive to conventional scaling and root planing over Curcumin application . Moreover , multiple adjunctive applications of photodynamic therapy are more beneficial than single application in reducing clinical & microbiological parameters 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 AIM This split-mouth double-masked r and omized controlled clinical study evaluated the effectiveness of photoactivated disinfection ( PAD ) using light-emitting diode ( LED ) as an adjunct in the management of patients affected by moderate to severe chronic periodontitis . MATERIAL S AND METHODS Sixteen patients affected by moderate to severe chronic periodontitis were enrolled . After scaling and root planing ( SRP ) , each quadrant was assigned to one of the following groups : LED group ( 625 - 635 nm , maximum power density : 2000 mW/cm(2 ) ) , photosensitizer group ( tolouidine blue O , 0.1 mg/ml ) , PAD group ( photosensitizer and LED ) and control group ( no adjunctive treatment ) . The adjunctive treatments were repeated after 7 and 14 days . The clinical parameters of bleeding on probing , probing pocket depth and clinical attachment level were measured at baseline and 1 and 3 months after SRP . RESULTS At 1 and 3 months , all groups showed significant improvements with regard to all clinical parameters compared to baseline ( all p : < 0.001 ) . There were no significant differences among groups in terms of changes of clinical parameters in any time interval ( all p > 0.05 ) . CONCLUSION The application of PAD using LED with the current setting did not have additional effects on clinical parameters in patients diagnosed with moderate to severe chronic periodontitis compared with SRP alone Recent pre clinical and clinical data have suggested the potential benefit of photodynamic therapy ( PDT ) in the treatment of periodontitis . However , currently , there are very limited data from controlled clinical trials evaluating the effect of PDT in the treatment of periodontitis . The aim of the present study was to evaluate the clinical and microbiological effects of the adjunctive use of PDT in non-surgical periodontal treatment in patients receiving supportive periodontal therapy . Twenty-four patients receiving regularly supportive periodontal therapy were r and omly treated with either subgingival scaling and root planing followed by a single episode of PDT ( test ) or subgingival scaling and root planing alone ( control ) . The following parameters were evaluated at baseline and at 3 months and 6 months after therapy : full mouth plaque score ( FMPS ) , full mouth bleeding score ( FMBS ) , bleeding on probing ( BOP ) at experimental sites , probing pocket depth ( PPD ) , gingival recession ( REC ) , and clinical attachment level ( CAL ) . Primary outcome variables were changes in PPD and CAL . Microbiological evaluation of Aggregatibacter actinomycetemcomitans ( A.a . ) , Porphyromonas gingivalis ( P.g . ) , Prevotella intermedia ( P.i . ) , Tannerella forsythensis ( T.f . ) , Treponema denticola ( T.d . ) , Peptostreptococcus micros ( P.m . ) , Fusobacterium nucleatum ( F.n . ) , Campylobacter rectus ( C.r . ) , Eubacterium nodatum ( E.n . ) , Eikenella corrodens ( E.c . ) , and Capnocytophaga species ( C.s . ) was also performed at baseline and at 3 months and 6 months after therapy , using a commercially available polymerase chain reaction test . No differences in any of the investigated parameters were observed at baseline between the two groups . At 3 months and 6 months after treatment , there were no statistically significant differences between the groups in terms of PPD , CAL and FMPS . At 3 months and 6 months , a statistically significantly higher improvement of BOP was found in the test group . At 3 months after therapy , the microbiological analysis showed a statistically significant reduction of F.n . and E.n . in the test group . At 6 months , statistically significantly higher numbers of E.c . and C.s . were detected in the test group . The additional application of a single episode of PDT to scaling and root planing failed to result in an additional improvement in terms of PPD reduction and CAL gain , but it result ed in significantly higher reduction of bleeding scores than following scaling and root planing alone OBJECTIVE The aim of the present study was to compare the effectiveness of a photodisinfection process to that of scaling and root planing ( SRP ) for non-surgical periodontal treatment . METHODOLOGY Thirty-three subjects with moderate to advanced periodontal disease were r and omly treated in one of three study arms with either photodisinfection ( PD ) alone ( Group 1 ) using a diode laser and photosensitizer combination , with SRP alone ( Group 2 ) , or with SRP and PD combined ( Group 3 ) . Clinical assessment s of bleeding on probing ( BOP ) , probing pocket depth ( PPD ) , and clinical attachment level ( CAL ) were made at baseline , three weeks , six weeks , and 12 weeks following therapy . RESULTS No difference in any of the investigated parameters was observed at baseline between the three groups . The mean value of BOP decreased in the PD group ( Group 1 ) from baseline by 71 % at six weeks and 73 % at 12 weeks , and in the SRP alone group ( Group 2 ) from baseline by 43 % at six weeks and 56 % at 12 weeks . The BOP in the combined SRP + PD group ( Group 3 ) decreased from baseline by 65 % at six and 59 % at 12 weeks . The sites treated with PD alone demonstrated mean CAL gains of 0.09 + /- 0.38 mm and 0.14 + /- 0.65 mm at six and 12 weeks , respectively . Those sites treated with SRP alone demonstrated mean CAL gains of 0.37 + /- 0.34 mm and of 0.36 + /- 0.35 mm at six and 12 weeks , respectively . The final group of SRP + PD demonstrated mean CAL gains of 0.92 + /- 0.62 mm and 0.86 + /- 0.61 mm at six and 12 weeks , respectively ( p < 0.01 for six weeks and p < 0.02 for 12 weeks when compared to SRP alone ) . The sites treated with PD alone demonstrated mean PPD reductions of 0.69 + /- 0.33 mm and of 0.67 + /- 0.44 mm at six and 12 weeks , respectively . Those sites treated with SRP alone demonstrated mean PPD reductions of 0.78 + /- 0.47 mm and 0.74 + /- 0.43 mm at six and 12 weeks , respectively . The final group of SRP + PD demonstrated mean PPD reductions of 1.16 + /- 0.39 mm and 1.11 + /- 0.53 at six and 12 weeks , respectively ( p < 0.06 for six weeks and p < 0.05 for 12 weeks when compared to SRP alone ) . CONCLUSION Within the limits of the present study , it can be concluded that SRP combined with photodisinfection leads to significant improvements of the investigated parameters over the use of SRP alone BACKGROUND There is an ongoing controversy on the benefits of treatment protocol s , including dental lasers and photodynamic therapy ( PDT ) . The purpose of this study is to compare the local biologic effects of PDT , diode soft laser ( DSL ) therapy , and conventional deep scaling and root planing ( SRP ) in residual pockets . METHODS Thirty-two individuals were included based on a history of previous treatment for periodontitis and the persistence of sites with probing depths > 4 mm and bleeding on probing . Residual pockets were debrided with an ultrasonic device and then r and omly assigned either to PDT , DSL , or SRP . Gingival crevicular fluid was collected before treatment , after 14 days , and at 2 and 6 months . Levels of 13 cytokines and nine acute-phase proteins were measured using a bead-based multiplexing analysis system . RESULTS Treatment with PDT , DSL , or SRP led to significant changes in several cytokines and acute-phase proteins : Compared with baseline , levels of interleukin-17 , basic fibroblast growth factor , granulocyte colony-stimulating factor , granulocyte macrophage colony-stimulating factor , and macrophage inflammatory protein 1-α were lower 14 days and 2 months after treatment . Except for granulocyte colony-stimulating factor , these differences remained significant throughout the observation period . The levels of five acute-phase proteins ( α-2 macroglobulin , haptoglobin , serum amyloid P , procalcitonin , and tissue plasminogen activator ) were significantly higher at 6 months than at baseline . No significant differences were observed among the three treatment modalities at any time point for any biochemical parameter . CONCLUSIONS Levels of several cytokines and acute-phase proteins significantly changed after treatment regardless of treatment modality . There was no evidence for a specific DSL- or PDT-enhanced expression of inflammatory mediators Residual pockets are challenging sites that require additional periodontal therapy . The aim of this study was to evaluate the effect of a single photodynamic therapy ( PDT ) as an adjunct to scaling and root planning ( SRP ) in residual pockets in single-rooted teeth . A blind , split-mouth , r and omized controlled clinical trial was conducted in systemically healthy subjects presenting at least two residual pockets ( probing pocket depth ( PPD ) ≥5 mm with bleeding on probing ( BoP ) ) in single root teeth in supportive periodontal therapy . The selected sites were assigned to receive ( 1 ) PDT + SRP or ( 2 ) SRP . In sites treated by PDT as adjunctive to SRP , the laser system included a h and held battery-operated diode laser with a wavelength of 660 nm , a power output of 60 mW , and energy density of 129 J/cm2 , together with methylene blue as a photosensitizer ( 10 mg/ml ) . Clinical parameters were assessed at baseline and 3 months post-therapies . Clinical parameters improved significantly after both therapies ( p < 0.05 ) , whereas higher probing pocket depth reduction and clinical attachment level gain were observed in the PDT + SRP group at 3 months ( p < 0.05 ) . In addition , sites treated by the combined approach yielded a significant reduction in the number of sites with PPD < 5 mm without BoP after 3 months compared to sites treated by conventional SRP alone ( p < 0.05 ) . PDT as an adjunctive to mechanical debridement demonstrated additional clinical benefits for residual pockets in single-rooted teeth and may be an alternative therapeutic strategy in supportive periodontal maintenance BACKGROUND This study investigates the effect of photodynamic therapy ( PDT ) as monotherapy during supportive periodontal therapy . METHODS A split-mouth , r and omized controlled trial was conducted in patients with chronic periodontitis ( N = 22 ) presenting at least three residual pockets ( probing depth [ PD ] ≥5 mm with bleeding on probing [ BOP ] ) . The selected sites r and omly received the following : 1 ) PDT ; 2 ) photosensitizer ( PS ) ; or 3 ) scaling and root planing ( SRP ) . At baseline and 3 and 6 months , clinical , microbiologic ( real-time polymerase chain reaction analyses ) , cytokine pattern ( multiplexed bead immunoassay ) , and patient-centered ( regarding morbidity ) evaluations were performed . RESULTS All therapies promoted similar improvements in clinical parameters throughout the study ( P < 0.05 ) , except that BOP was not reduced in the PS protocol ( P > 0.05 ) . Lower levels of Aggregatibacter actinomycetemcomitans were observed in the PDT and SRP protocol s at 3 months when compared with the PS protocol ( P < 0.05 ) . An inferior frequency detection of Porphyromonas gingivalis was observed in the PDT protocol at 3 and 6 months and in the SRP protocol at 6 months from baseline ( P < 0.05 ) . In addition , PDT protocol presented inferior frequency of P. gingivalis at 3 months when compared with the other therapies ( P < 0.05 ) . Only patients in the PDT protocol exhibited augmented levels of anti-inflammatory interleukin (IL)-4 and reduced proinflammatory IL-1β and IL-6 throughout the study ( P < 0.05 ) . Intergroup analyses showed reduced IL-10 and increased interferon-γ and IL-1β levels in the PS protocol when compared with the other therapies during follow-ups ( P < 0.05 ) . No differences in morbidity were observed between the therapies ( P > 0.05 ) , although the need for anesthesia was higher in SRP-treated sites ( P < 0.05 ) . CONCLUSION PDT as an exclusive therapy may be considered a non-invasive alternative for treating residual pockets , offering advantages in the modulation of cytokines BACKGROUND There are limited clinical experiments addressing the effects of photodynamic therapy ( PDT ) as an adjunct to conventional scaling and root planing ( SRP ) on clinical and biologic features of periodontitis . This trial compares the clinical parameters and cytokine profiles in gingival crevicular fluid of patients with moderate-to-severe chronic periodontitis ( CP ) who have been treated using SRP alone or SRP + PDT . METHODS Twenty-two patients with two contralateral teeth affected with moderate-to-severe CP were selected . After SRP , the participants ' teeth were r and omized to receive either no further treatment or a single application of PDT using a 638-nm laser and toluidine blue . Although the change in probing depth was the primary outcome , bleeding on probing , clinical attachment level , gingival recession , interleukin-1β , tumor necrosis factor (TNF)-α , and matrix metalloproteinase 8 and 9 were also evaluated at baseline and 3 months postintervention . An oral rinse assay was also performed to determine the total levels of oral polymorphonuclear cells ( PMNs ) before and 3 months after the treatments . RESULTS Within each group , significant improvements ( P < 0.001 ) were found for all variables in 3-month follow-up compared with baseline . Only TNF-α was significantly improved in the PDT + SRP versus SRP group . Total levels of PMNs were reduced for all patients compared with baseline levels ( P < 0.001 ) . CONCLUSION In patients with CP , a single application of PDT ( using a 638-nm laser and toluidine blue ) did not provide any additional benefit to SRP in terms of clinical parameters or inflammatory markers 3 months following the intervention Antimicrobial photodynamic therapy ( aPDT ) was introduced as a promising adjuvant therapy on the periodontal treatment . The aim of this study was to evaluate the effect of aPDT on inflammatory mediator levels in residual periodontal pockets of patients with severe chronic periodontitis under periodontal maintenance , during 12 months follow-up . A r and omized controlled trial study was conducted in 28 patients with severe chronic periodontitis . After non-surgical periodontal treatment , patients with at least four teeth with residual pocket probing depth ( PPD ) ≥4 mm were r and omly assigned to either aPDT or control group . The aPDT ( low power laser : 660 nm , 40 mW , 90 J/cm2 , methylene blue 0.01 % ) was performed at baseline and 3 , 6 , and 9 months . Clinical parameters were collected before and 3 and 12 months after the intervention , and gingival crevicular fluid was collected in the same times , including 1 week after the intervention . Immunological evaluation was carried out using the Luminex assay which quantified the expression of ten cytokines : interleukin (IL)-1α , IL-1β , IL-8 , IL-1ra , fibroblast growth factor ( FGF ) , vascular endothelial growth factor ( VEGF ) , interferon (IFN)-γ , tumor necrosis factor (TNF)-α , IL-4 , and IL-10 . All clinical variables showed significant improvement for both groups , but there was no statistical difference between groups with no clinical benefits . IL-1α , IL-1β , IL-8 , and VEGF showed significant differences ( p < 0.05 ) between groups , whereas IL-1ra mediators , IFN-γ , and IL-10 demonstrated a statistical difference ( p < 0.01 ) over time in the same group . At any time , FGF , IL-4 , and TNF-α showed no statistical difference between groups ( p > 0.05 ) . aPDT therapy can improve the benefits on inflammation control during the periodontal maintenance BACKGROUND The current study was devised with the objective of using a split-mouth , controlled clinical trial to compare conventional mechanical debridement ( scaling and root planing ) treatment ( T1 ) with conventional mechanical treatment followed by photodynamic therapy ( PDT ) ( T2 ) in patients with severe periodontitis . METHODS Four PDT sessions were completed , and clinical parameters such as bleeding upon probing ( BOP positive ) , plaque index ( PI ) , probing pocket depth ( PPD ) and clinical attachment loss ( CAL ) were evaluated before and after the treatment series . In addition , gingival biopsies were collected at the start and finish of treatment , and were used for qPCR gene expression analysis of TNFA , IL1B , IL8 , IL10 , IL17 , MMP13 , FGF2 , RANK , RANKL and OPG . RESULTS The clinical results showed a significant improvement in BOP with treatment T2 ( p=0.03 ) . The molecular data showed an up-regulation of FGF2 , RANK and OPG gene expression after T2 . The expression levels of the other genes were not significantly different between T1 and T2 . PDT increased the expression of RANK and OPG , which could indicate a reduction in osteoclastogenesis . Furthermore , the use of PDT in conjunction with conventional treatment significantly increased the expression of FGF2 , which has an important role in the periodontal repair process . CONCLUSIONS PDT technology could be a means to improve conventional periodontitis treatment . Our results suggest that PDT acts in part by controlling bone resorption and increasing the expression of genes important for tissue repair OBJECTIVE The purpose of this study was to evaluate the clinical effects of photodynamic therapy ( PDT ) for scaling and root planing ( SRP ) in the treatment of chronic periodontitis . BACKGROUND DATA PDT has become a potential treatment of infectious diseases with the development of laser medicine . However , there are very limited data from clinical trials to evaluate the effect of PDT in the treatment of periodontitis . MATERIAL S AND METHODS Fifty-eight patients with chronic periodontitis were included and divided into three groups . They were treated with SRP alone , SRP followed by one PDT , or SRP followed by two PDT treatments . PDT was performed at sites with a probing depth ( PD ) ≥5 mm by using Periowave(TM ) therapy . Periodontal values of bleeding on probing ( BOP ) , PD , and clinic attachment loss ( CAL ) were examined at baseline , 6 wk after treatment , and 12 wk after treatment . RESULTS Compared with the baseline , sites with baseline PD ≥5 mm in all three groups showed significant reductions of PD , CAL , and BOP at 6 and 12 wk after treatment . Although there were no differences between the three groups for PD and CAL in all three examinations , the presence of BOP sites at 12 wk , but not 6 wk , after SRP treatment significantly decreased in groups with PDT in comparison with SRP alone . CONCLUSION PDT may serve as an adjunctive therapy to SRP treatment in periodontal pockets with PD ≥5 mm to reduce the presence of bleeding in these lesions AIM Comparing the efficacy of photoablative and photodynamic diode laser in adjunct to scaling -root planing ( SRP ) and SRP alone for the treatment of chronic periodontitis . MATERIAL S AND METHODS Twenty-six patients were studied . Maxillary left or right quadrants were r and omly assigned to sham-laser treatment + SRP or laser + SRP . This consisted of photoablative intra/extra-pocket de-epithelization with diode laser ( λ = 810 nm ) , followed by single SRP and multiple photodynamic treatments ( once weekly , 4 - 10 applications , mean ± SD : 3.7 ± 2.4 ) using diode laser ( λ = 635 nm ) and 0.3 % methylene blue as photosensitizer . The patients were monitored at days 0 and 365 by clinical assessment ( probing depth , PD ; clinical attachment level , CAL ; bleeding on probing , BOP ) and at days 0 , 15 , 30 , 45 , 60 , 75 , 90 , 365 by cytofluorescence analysis of gingival exfoliative sample s taken in proximity of the teeth to be treated ( polymorphonuclear leukocytes , PMN ; red blood cells , RBC ; damaged epithelial cells , DEC ; bacteria ) . RESULTS At day 365 , compared with the control quadrants , the laser + SRP therapy yielded a significant ( p < 0.001 ) reduction in PD ( -1.9 mm ) , CAL ( -1.7 mm ) and BOP ( -33.2 % bleeding sites ) , as well as in bacterial contamination - especially spirochetes - and PMN and RBC shedding in the gingival sample s ( p < 0.001 ) . CONCLUSIONS Diode laser treatment ( photoablation followed by multiple photodynamic cycles ) adjunctive to conventional SRP improves healing in chronic periodontitis patients BACKGROUND AND OBJECTIVE Photodynamic therapy ( PDT ) has been used as a therapeutic alternative to treat periodontitis , especially in challenging sites that require additional periodontal therapy such as residual pockets . The aim of this split-mouth r and omized trial was to evaluate the microbiological and clinical effects of PDT on non-surgical treatment of unresponsive pockets . STUDY DESIGN / MATERIAL S AND METHODS A split-mouth , r and omized controlled clinical trial was conducted in 15 patients presenting at least two residual pockets ( probing pocket depth [ PPD ] ≥5 mm with bleeding on probing [ BoP ] ) in single-rooted teeth in supportive periodontal therapy . The selected sites r and omly received : ( 1 ) SRP + PDT : scaling and root planing combined with photodynamic therapy ( methylene blue as a photosensitizer ) , or ( 2 ) SRP : scaling and root planing alone . The concentrations of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were evaluated using a Real-time PCR technique at baseline and 3 , 7 , 14 , and 90 days . Clinical parameters were assessed at baseline and 3 months post-therapies . RESULTS Both treatments promoted clinical improvements , with additional benefits to the SRP + PDT group in PPD reduction and clinical attachment level gain ( P < 0.05 ) after 3 months . Only the SRP + PDT group exhibited a statistically significant reduction in the levels of A. actinomycetemcomitans on the 3rd and 7th days after therapy ( P < 0.05 ) , and a lower concentration of this pathogen was detected at 7 days in the SRP + PDT group when compared to the other therapy ( P < 0.05 ) . CONCLUSION The combined therapeutic approach SRP + PDT may reduce A. actinomycetemcomitans levels for a short-term period , associated with additional improvement in clinical parameters in treating residual pockets . Lasers Surg . Med . 48:944 - 950 , 2016 . © 2015 Wiley Periodicals , |
13,556 | 31,158,298 | Combined antidepressant plus benzodiazepine therapy was more effective than antidepressants alone in improving depression severity , response in depression and remission in depression in the early phase .
However , these effects were not maintained in the acute or the continuous phase .
Combined therapy result ed in fewer dropouts due to adverse events than antidepressants alone , but combined therapy was associated with a greater proportion of participants reporting at least one adverse effect . | BACKGROUND Anxiety frequently coexists with depression and adding benzodiazepines to antidepressant treatment is common practice to treat people with major depression .
However , more evidence is needed to determine whether this combined treatment is more effective and not any more harmful than antidepressants alone .
It has been suggested that benzodiazepines may lose their efficacy with long-term administration and their chronic use carries risks of dependence .
This is the 2019 up date d version of a Cochrane Review first published in 2001 , and previously up date d in 2005 .
This up date follows a new protocol to conform with the most recent Cochrane methodology guidelines , with the inclusion of ' Summary of findings ' tables and GRADE evaluations for quality of evidence .
OBJECTIVES To assess the effects of combining antidepressants with benzodiazepines compared with antidepressants alone for major depression in adults . | Two hundred and forty neurotic out- patients were allocated to no diagnostic category but were rated in terms of observer and self ratings of both depression and anxiety at weekly intervals during a 4-week trial of amitriptyline , diazepam , amitriptyline and diazepam , and placebo . The sample could not be divided into anxious and depressed groups on the basis of the clinical picture . The outcome tended to be good irrespective of medication but the significant drug effects found were due to amitriptyline and concerned measures of anxiety as well as depression . It is concluded that a distinction between anxiety and depression in neurotic out- patients is of no practical value with regard to drug treatment Abstract . Rationale : A large proportion of patients with major depression do not respond sufficiently to any first-line treatment . Objectives : The aim of this study was to compare a strategy of sertraline dose increase with a strategy of adding mianserin in patients with major depression insufficiently responding to 6 weeks of open treatment with sertraline , controlling for the effect of an extended duration of treatment . Methods : One thous and six hundred and twenty-nine patients , 18–65 years of age , with major depression scoring at least 18 on the 17-item Hamilton depression scale ( HDS ) were treated openly with 50 mg/day sertraline , and patients who after 4 weeks had not responded ( achieving at least a 50 % reduction in score on the HDS ) were treated with 100 mg/day sertraline for an additional 2-week period . The patients who had still not responded were then r and omised to double-blind treatment for an additional 5 weeks with either 100 mg/day sertraline plus placebo , 200 mg/day sertraline plus placebo or 100 mg/day sertraline plus 30 mg/day mianserin . Results : After 6 weeks of open treatment , 60 % had responded and 22 % had dropped out , leaving 295 non-responding patients ( 18 % ) for r and omisation . In the intention-to-treat- analysis , continuing the treatment with 100 mg/day sertraline result ed in response in 70 % of the non-responders , similar to the response rate ( 67 % ) obtained in the patients who had mianserin added . However , increasing the sertraline dose to 200 mg/day result ed in a lower response rate at 56 % ( P<0.05 ) . Similar results were seen in the completers . A substantial increase in the accumulated response rate from week 6 to week 8 was seen . There was no influence of baseline variables , including the presence of melancholic features on the overall post-r and omisation response rate . Conclusion : After 6 weeks of insufficient antidepressant treatment with 50–100 mg/day sertraline , a continued treatment with 100 mg/day sertraline can be considered until at least week 8 before considering changing strategy , unless the condition deteriorates CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data This study examines the scientific basis for mental health intervention programs in primary care . The validity of five underlying assumptions is evaluated , using the results of a naturalistic study covering a representative sample of 25 Dutch family practice s and data from the literature . Our findings corroborate the validity of the assumptions . Firstly , our study indicates that mental disorders are indeed very prevalent in primary care setting s. Secondly , we find that a substantial proportion of mental disorders is not recognized by the general practitioner ( GP ) . Thirdly , our data show that mental disorders in primary care are not transient or self-limiting . Fourthly , it is shown that only half of the GP attenders with a mental disorder receive some form of mental health treatment in the 14 months after their index consultation . Finally , our data suggest that mental disorders , when identified , can be treated effectively in primary care . These findings are in general agreement with the literature . In the discussion we underscore the need for public health intervention programs targeted at primary care providers . Training programs for general physicians must be directed at improving recognition and diagnosis and at enhancing the availability and quality of mental health interventions . The effectiveness of these programs has to be tested in r and omized trials Four hundred and thirty-four patients suffering from mild to moderate depression were recruited into a double-blind multicentre general practice study and r and omly received either Limbitrol ( 25 mg amitriptyline and 10 mg chlordiazepoxide ) or amitriptyline 25 mg in matching white capsules given as a single night-time dose . The dose was titrated to a maximum of four capsules per night . Patients were assessed on entry and at 7-day intervals for depressive state ( Hamilton Rating Scale for Depression ) , cardiovascular effect and side-effects for 28 days . Self- assessment s of depression and anxiety using the Leeds Scale were made in the form of a patient question naire . Both groups showed significant improvement at each visit and significantly more patients improved after 7 days in the Limbitrol group . There was no significant difference in treatment over all between groups , in the incidence of side-effects , or in the effects on the heart Objective : To assess , in depressed patients , the clinical benefit of mianserin augmentation of fluoxetine or the the benefit of switching treatment from fluoxetine to mianserin The primary goal of this study was to determine whether the amphetamine challenge test ( ACT ) response , as measured by a subjective rating scale , the How I Feel Scale ( HIF ) , could predict antidepressant treatment outcome . Following a 1-day non-blind ACT with dextroamphetamine ( d-AMPH ) , patients were treated double-blind for 6 weeks with either desipramine , alprazolam , or a desipramine-alprazolam combination . Regression ( true score ) analyses were carried out on pre- and post-ACT HIF scores and on baseline and end of study Hamilton Depression Rating Scale ( HDRS ) scores to determine the magnitudes of improvement measured in response to the ACT and antidepressant treatment , respectively . Regression analyses were performed on the residuals ( true scores of improvement ) to determine the best fitting ( linear ) prediction equation . Improvement in the HIF total score predicted HDRS improvement for the whole sample . Possible sources of error contributing to the outcome are identified and the results are discussed in relation to previous clinical investigations of the potential usefulness of the ACT as a predictor of antidepressant response BACKGROUND Clonazepam cotherapy of fluoxetine was previously demonstrated to accelerate efficacy over the first 3 weeks of treatment . A new 18-week double-blind study attempted to replicate these findings to determine whether superiority would extend to 3 months and assess risks of extension . METHOD Fifty outpatient volunteers aged 18 - 65 from Seattle and Portl and with moderate-marked depression received fluoxetine ( 20 mg ) doubled at 6 weeks if needed ; half took clonazepam ( 0.5 mg ) and half took an identical placebo , 1 or 2 tablets adjusted during the first 2 weeks , until a 3-week taper at 3 months . RESULTS No serious adverse events and no special problems with sedation or discontinuation were noted . Cotherapy was superior to fluoxetine monotherapy at Day 7 for HAM-D ( t=2.03 , df=48 , P<0.05 ) and CGI-I ( 32 vs. 4 % responders , P<0.03 , Fisher Exact Test ) but not otherwise . Cotherapy was effective in reducing insomnia but not anxiety or core symptoms ( low mood , suicidality , reduced interest ) . The only significant benefit of extending treatment was a more rapid response to increased fluoxetine at 6 weeks manifested in a mean HAM-D of 9.0 and CGI-I responder rate of 76 % after 8 weeks compared to 16 weeks for monotherapy . LIMITATIONS Small sample size ( N=50 ) limited power and rendered conclusions tentative . CONCLUSIONS Extended clonazepam cotherapy of fluoxetine appeared safe and effective for depressed out patients : it was superior to fluoxetine alone early in treatment and again following fluoxetine dose increase . Cotherapy might be considered at the start of fluoxetine treatment , especially for those with insomnia , and when a dose increase of fluoxetine is anticipated In a multicenter , placebo-controlled , clinical trial , the efficacy of Limbitrol was compared with that of its components , amitriptyline and chlordiazepoxide . All patients had a diagnosis of primary depression . Data from 279 patients were evaluated using the Hamilton depression scale , the Beck depression inventory , and physician and patient global change measures .Statistically significant differences favoring Limbitrol occurred after 1 week of treatment , and a trend in favor of Limbitrol continued throughout the remaining 3 weeks . In most efficacy comparisons , the combination was as good as , or better than , amitriptyline alone . It was superior to chlordiazepoxide alone after 2 and 4 weeks of treatment . Each component produced an independent contribution to the total therapeutic effect : the chlordiazepoxide effect was more prominent in the first 2 weeks and the amitriptyline effect in the latter 2 weeks . A trend favoring amitriptyline over chlordiazepoxide was evident by week 4.The overall incidence of side effects was comparable in both Limbitrol- and amitriptyline-treated groups . Limbitrol-treated patients exhibited more sedation , but significantly fewer Limbitrol patients discontinued treatment prematurely because of side effects 1 . Ninety healthy adult men participated in a study of the effects on performance of 60 mg fluoxetine , 50 mg amitriptyline or placebo , alone and in combination with 5 mg diazepam or placebo . 2 . In a 2X3 factorial design study , groups of 15 Ss received one of six possible treatment combinations . 3 . Ss were tested with a battery of laboratory tests at two post-dosing times . 4 . Amitriptyline impaired the performance of all tasks . When diazepam was added to the amitriptyline treatment , the impairment of three tasks increased . Diazepam alone produced impairment on two measures . 5 . Fluoxetine alone impaired no task ; some impairment occurred with the fluoxetine-diazepam combination Chlordiazepoxide-amitriptyline ( Limbitrol ) has been shown to be more rapidly effective than amitriptyline alone for treating depression . A double-blind , r and omized study was design ed to compare the effects of Limbitrol and amitriptyline on insomnia , anxiety , and depression . The rate of improvement of symptoms was faster with Limbitrol . No differences were noted between groups in the degree or rate of improvement of the sleep laboratory parameters nor in sleep Stages 1 to 4 . Percentages of rapid eye movement ( REM ) sleep and REM latency were similarly affected by the drugs , but REM density showed a significantly greater decrease with Limbitrol . Phasic REM factors may be crucial in the role of REM sleep and depression BACKGROUND Undertreatment of depression appears widespread but the available literature is limited to North American and European countries . We aim ed to examine the treatment received by patients with major depression in Japan and to eluci date any predictor of their treatment level . METHODS A naturalistic , prospect i ve follow-up study of an inception cohort of subjects with mood disorders was undertaken in psychiatric departments of 13 university hospitals , those of six general hospitals , three mental hospitals and one community mental health center from all over Japan . A total of 95 patients without any prior antidepressant treatment were diagnosed with major depression according to DSM-IV and were followed up every month until treatment termination and every 6 months thereafter . RESULTS The follow-up information was available in 98 to 97 % of the cohort . The proportion of patients receiving less than 125 mg/day of imipramine or equivalent reached 69 % ( 95 % CI : 58 - 78 % ) at 1 month and 67 % ( 95 % CI : 54 - 77 % ) at 6 months . A few clinical variables were significantly associated with inadequate antidepressant prescription but altogether they explained only 5 to 14 % of the variance observed . CONCLUSIONS Japan was no exception to the other industrialized countries in its less than optimal provision of treatment to major depression and its lack of explanatory predictors for this common practice BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 21-point index with 5 domains : r and omization , outcomes , eligibility criteria , interventions and statistical issues . Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant . For studies that did not explicitly identify a primary outcome , we defined a " positive " study as one with at least 1 statistically significant outcome measure . We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results , while controlling for study quality and sample size . RESULTS Among the 332 r and omized trials , there were 158 drug trials , 87 surgical trials and 87 trials of other therapies . In 122 ( 37 % ) of the trials , authors declared industry funding . An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 - 3.5 ) . The association remained significant after adjustment for study quality and sample size ( adjusted OR 1.8 , 95 % CI 1.1 - 3.0 ) . There was a nonsignificant difference between surgical trials ( OR 8.0 , 95 % CI 1.1 - 53.2 ) and drug trials ( OR 1.6 , 95 % CI 1.1 - 2.8 ) , both of which were likely to have a pro-industry result ( relative OR 5.0 , 95 % CI 0.7 - 37.5 , p = 0.14 ) . INTERPRETATION Industry-funded trials are more likely to be associated with statistically significant pro-industry findings , both in medical trials and surgical interventions Two double-blind four-way crossover studies are reported , comparing the antidepressant effect of 14-day courses of : viloxazine , viloxazine with a tranquillizer either perphenazine or diazepam or tranquillizer alone , against a placebo . In one study the antidepressant effect of viloxazine at a dose of 150 mg daily was statistically greater than that of placebo , whilst in the second study viloxazine was statistically superior to diazepam ( 15 mg daily ) . In depressed patients with a clear anxiety component , viloxazine alone seemed preferable to a combination with a tranquillizer as such a combination did not produce an enhanced clinical effect and the incidence of side-effects was possibly increased . Viloxazine was generally well tolerated and side-effects , when they occurred , were generally a mild upper gastro-intestinal disturbance ABSTRACT — Sixty‐three non‐agitated depressed out‐ patients were selected according to the Feighner‐Robins‐Guze criteria for primary depressions for a double‐blind , between‐patient r and omized study for an 8 week duration . All the patients were treated with imipramine following a fixed dose schedule for the first 2 weeks and thereafter according to clinical response ( 100‐200 mg/day ) . This treatment was combined with either placebo , diazepam ( 10 mg/day ) or dixyrazine ( 50 mg/day ) . The serum concentration of imipramine both at 2 weeks and later was significantly higher ( P < 0.05 ) in the group treated with dixyrazine than in the other two groups . In the group treated with diazepam , the serum levels of imipramine and desipramine were significantly lower than in the placebo group . The serum concentrations of diazepam , desmethyldiazepam and dixyrazine were almost unchanged during the study . No significant correlation was found between the dosage and the serum concentration of imipramine or desipramine . The change in mean CPRS‐score correlated neither with the imipramine nor with the desipramine serum levels , it did correlate but negatively with the degree of side effects . The degree of side effects correlated positively with the serum concentration of desipramine Patients suffering from depression ( mostly depressive neurosis ) were admitted to a double‐blind study which compared the efficacy of a combination of nomifensine and clobazam with mianserin . Therapeutic efficacy was evaluated on the Hamilton Depression Rating Scale , Hamilton Anxiety Rating Scale , Clinical Global Impression Scale , physicians ' assessment s , Global Improvement and Treatment Emergent Symptom Scale for side‐effects . Assessment s were made before admission to the trial and on days 3 , 7 , 14 and 21 . Forty patients were r and omly allocated to two treatment groups . A case is made against polypharmacy and in particular against the use of benzodiazepine combinations in depression . Nineteen patients on nomifensine‐clobazam and 14 on mianserin completed the three‐week trial . At 7 , 14 and 21 days , the Hamilton Depression Rating Scale ( HDRS ) total scores were significantly improved for mianserin when compared with nomifensine‐clobazam . Similarly , at 7 and 14 days the Hamilton Anxiety Rating Scale ( HARS ) total scores were significantly better for mianserin thanfor the nomifensine‐clobazam combination . There were also significant improvements for mianserin on the HDRS sub‐scales of anxiety somatization , cognitive disturbance and sleep disturbance . There were no significant differences for HDRS somatic symptoms between treatment groups . Drowsiness was the most common side‐effect in both groups . The incidence of total side‐effects was 74 % for nomifensine‐clobazam and 71 % for the mianserin group In a 4 week study of the response of neurotic out patients to treatment with amitriptyline , diazepam , amitriptyline and diazepam , or placebo , clinical and psychophysiological variables and plasma levels of the drug were assessed . Clinical improvements were substantial in all treatment groups but clear relationships between clinical change , psychophysiological change and plasma levels of the drugs were not established . There was no relationship between plasma levels of the drugs and cigarette smoking . It is concluded that neither plasma levels of amitriptyline and diazepam nor change in skin conductance responsivity offer a useful guide to clinical response to drug treatment The antidepressant efficacy of alprazolam ( ALP ) was tested in a double-blind controlled comparison with desipramine ( DMI ) and an ALP-DMI combination in out patients diagnosed with major depressive disorder by Research Diagnostic Criteria ( 90 % met criteria for endogenous subtype ) . Following a placebo period of at least 1 week , subjects who continued to meet severity criteria defined by Hamilton Depression Rating Scale ( HDRS ) scores were administered oral doses of the active medication ( N = 79 ) , in a dose ratio of 1 mg ALP:50 mg DMI:1 mg ALP + 50 mg DMI . Treatment continued for 6 weeks , and all subjects who completed at least 2 weeks ( N = 69 ) were included in endpoint analyses . Following the placebo baseline , symptoms were rated again at day 5 and at the end of weeks 1 , 2 , 4 , and 6 . Final doses averaged 4.6 ± 1.3 mg for the ALP group , 230 ± 61 mg for the DMI group , and 4.6 ± 1.2 mg ALP + 229.5 ± 1.2 mg DMI for the combination group . The final outcome was a comparable degree of improvement at the end-point among the three treatment groups on measures of depression ( HDRS and Beck Depression Inventory ) , anxiety ( Hamilton Anxiety Rating Scale ) , and global improvement ( Global Assessment Scale , and Physician and Patient Global Impressions ) . A similar outcome was found for the subgroup of patients who completed all 6 weeks ( N = 56 ) . Endpoint analyses also showed that ALP-treated subjects responded sooner and continued to show improvement throughout the course of the study on measures of depression , anxiety , and global status . These results suggest that ALP alone is as effective as a st and ard tricyclic for the acute treatment of patients with major depressive disorder and that significant improvement may occur within the first week of medication . Side effect profiles were compared among treatment groups and are discussed , as are other clinical studies that have investigated ALP 's potential antidepressant efficacy . ( J Clin Psychopharmacol 1987;7:295—310 OBJECTIVE To determine the clinical predictors and rate of relapse for major depression in primary care . DESIGN A cohort study of subjects in 2 r and omized trials of depressed patients diagnosed and prescribed antidepressant medicine by primary care physicians . Baseline , 7-month , and 19-month assessment s were conducted . SETTING A large primary care clinic of a staff-model health maintenance organization . PATIENTS Two hundred fifty-one primary care patients who did not satisfy Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition ( DSM-III-R ) criteria for major depression at 7 months . MAIN OUTCOME MEASURES Relapse was defined as ( 1 ) satisfying DSM-III-R criteria for major depression at 19 months , or ( 2 ) reporting an interval episode of 2 weeks or more of depressed mood and symptoms between 7 and 19 months . Predictors examined included demographic characteristics , medical comorbidity , disability , and psychological symptoms . Depressive symptoms were measured by Inventory of Depressive Symptoms and Hopkins Symptoms Checklist . RESULTS Of the patients , 37.1 % reported relapse of depression in the 12-month relapse-risk period . The 2 major risk factors associated with relapse were ( 1 ) persistence of subthreshold depressive symptoms 7 months after the initiation of antidepressant therapy ( odds ratio , 3.3 ; 95 % confidence interval , 2.74 - 3.93 ) and ( 2 ) history of 2 or more episodes of major depression , or chronic mood symptoms for 2 years ( odds ratio , 2.1 ; 95 % confidence interval , 1.41 - 2.76 ) . Patients with both risk factors were approximately 3 times more likely to relapse than patients with neither . CONCLUSIONS The relapse rate among primary care patients treated for depression approached that of specialty sample s , with more than one third reporting relapse in 1 year . Clinical characteristics can help target high-risk patients for relapse prevention efforts This double-blind study involved the continuous ( six to 22 weeks ) treatment of 180 chronically anxious out patients with diazepam , 15 to 40 mg/day . Our findings indicate that a significant number of patients benefit from prolonged diazepam treatment and that tolerance to the anxiolytic effect of diazepam does not develop during a 22-week study period . The duration of continual treatment with sedative-benzodiazepines was clearly the most important determinant of withdrawal reactions . Patients treated continuously for less than eight months with sedative-benzodiazepines had an incidence of withdrawal of 5 % , whereas 43 % of patients treated for eight months or more demonstrated clear withdrawal reactions . While these withdrawal reactions produced considerable distress , they were neither life threatening nor incapacitating and did not include convulsions or psychotic reactions . In all cases , withdrawal reactions could be readily managed by gradually tapering the dose of the benzodiazepine The purpose of the present paper was to investigate the efficacy of augmentation of clomipramine ( CMI ) by t and ospirone in 36 untreated out patients with major depressive disorder . Twelve patients were treated with CMI and t and ospirone ( T group ) , 12 with CMI and diazepam ( D group ) and 12 with CMI alone ( C group ) for 6 weeks . No statistically significant differences in the percentage improvement of the Hamilton Depression Rating Scale ( 17 items ; HDRS-17 ) and the Hamilton Anxiety Rating Scale ( 14 items ; HARS-14 ) scores were shown among the three treatment groups . However , at 2 weeks , the percentage improvement of HDRS-17 score in the T group tended to be higher than that in the D and C groups , although there was no statistically significant difference among the three treatment groups . No change in plasma prolactin level or adverse events was induced by the addition of t and ospirone . These results suggest that 6 weeks of treatment with t and ospirone or diazepam was not effective for augmentation of CMI in major depressive disorder patients . However , augmentation of antidepressants by t and ospirone administration for a few weeks might induce early expression of antidepressive effects BACKGROUND SSRIs resolve depression slowly and may increase anxiety or insomnia . Adding clonazepam to fluoxetine sped response , raising the question of mechanism of action : reducing symptoms co-existing with depression , suppressing side-effects , and /or alleviating core depressive symptoms . METHOD Adult out patients r and omly assigned to double-blind treatment with fluoxetine 20 mg+placebo or fluoxetine+clonazepam 0.5 - 1.0 mg were assessed by a HAM-D anxiety cluster , sleep disturbance cluster , and core symptoms cluster . RESULTS No serious AEs were noted ; no cotherapy patients dropped for AEs . Cotherapy proved superior ( HAM-D total , anxiety cluster , sleep disturbance cluster ANOVA P<0.001 ; core symptoms P<0.011 ) . Treatment-emergent anxiety was reported for 25 % of placebo patients and 7 % of cotherapy patients ( P<0.037 ) ; sleep disturbance for 10 % of placebo patients and no cotherapy patients ( P<0.055 ) . Sedation and dry mouth were more common for cotherapy treatment ( P>0.20 ) . LIMITATIONS Extended treatment and refractory depression were not addressed . CONCLUSIONS Low-dose cotherapy of fluoxetine with clonazepam was safe and accelerated response over 21 days of treatment , decreasing anxiety and sleep disturbance as symptoms and partially suppressed them as SSRI side-effects ; it also modestly reduced core symptoms of low mood and loss of interest ABSTRACT – Sixty‐three out‐ patients suffering from primary non‐agitated depression were included in a double‐blind , between‐patient r and omized study . All patients were treated with imipramine ( 100–200 mg‐day ) combined with either placebo , diazepam ( 10 mg/day ) or dixyrazine ( 50 mg/day ) for 8 weeks . The clinical efficacy assessed with a subscale of CPRS was significantly ( p1≤0.05 ) better for the imipramine‐dixyrazine combination than for the imipramine‐diazepam or imipramine‐placebo combination . Serum concentration of imipramine was significantly higher ( p1≤0.05 ) in the group treated with dixyrazine than in the other two groups . Further , serum concentration of imipramine in the diazepam group was significantly lower ( p1≤0.05 ) than in the placebo group . At the end of the study , 67 % in both the placebo and the diazepam group and 86 % in the dixyrazine group were practically symptom‐free OBJECTIVE Because selective serotonin reuptake inhibitors ( SSRIs ) require 2 - 4 weeks to reach efficacy , the authors determined whether clonazepam augmentation of fluoxetine is superior to fluoxetine alone at the beginning of treatment for major depression . METHOD Eighty adult out patients with major depression who were rated as " moderately ill " or " markedly ill " on the Clinical Global Impression of Severity underwent 8 weeks of double-blind , r and omized treatment with fluoxetine , 20 mg/day for all patients initially and 40 mg/day if needed after 6 weeks . One-half of these patients received clonazepam , 0.5 mg h.s . adjusted to two tablets by day 10 if needed , and the remainder received placebo , likewise adjusted . Clonazepam/placebo was gradually discontinued during days 21 - 33 . Efficacy was evaluated by means of the Hamilton Depression Rating Scale , the Clinical Global Impression of Improvement , and a patient rating of global improvement . RESULTS The patients taking clonazepam improved significantly more during the first 3 weeks of treatment according to ratings on the Hamilton scale ( > or = 50 % improvement ) and the clinician- and patient-rated global improvement measures ( " much " or " very much " improved ) . Analysis of variance confirmed a significant effect of clonazepam for average Hamilton depression scores . No serious adverse events were found in either treatment group . Taper effects appeared modest and transitory . CONCLUSIONS Clonazepam augmentation of fluoxetine was superior to fluoxetine alone in the first 3 weeks of treatment . This strategy may reduce suffering during early SSRI treatment , may partially suppress SSRI side effects , may increase compliance , and could possibly reduce the risk of suicide Anxious depression , defined as major depressive disorder ( MDD ) accompanied by high levels of anxiety , seems to be both common and difficult to treat , with antidepressant monotherapy often yielding modest results . We sought to examine the relative benefits of antidepressant-anxiolytic cotherapy versus antidepressant monotherapy for patients with anxious depression versus without anxious depression . We conducted a post-hoc analysis of an existing data set ( N=80 ) , from a 3-week , r and omized , double-blind trial which demonstrated cotherapy with fluoxetine and clonazepam to result in superior efficacy than fluoxetine monotherapy in MDD . The present analysis involved examining whether anxious depression status served as a predictor and moderator of symptom improvement . Anxious depression status was not found to predict symptom improvement , or serve as a moderator of clinical improvement to cotherapy versus monotherapy . However , the advantage in remission rates in favor of cotherapy versus monotherapy was , numerically , much larger for patients with anxious depression ( 32.2 % ) than it was for patients without anxious MDD ( 9.7 % ) . The respective number needed to treat statistic for these two differences in response rates were , approximately , one in three for patients with anxious depression versus one in 10 for patients without anxious depression . The efficacy of fluoxetine-clonazepam cotherapy compared with fluoxetine monotherapy was numerically but not statistically enhanced for patients with anxious depression than those without anxious depression Some investigators have found benzodiazepines effective in the treatment of anxious depression and thus have argued that benzodiazepines were " antidepressants . " We review ed the literature on benzodiazepines in depressive disorders . Comparative studies indicate they are less effective than st and ard antidepressants in the treatment of several types of depressive illnesses . Although they display definite anxiolytic properties and may elevate mood , they exert limited effect on the core symptoms of endogenous depression . An argument is made that benzodiazepines are primarily anxiolytic rather than antidepressant BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline . Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias Recently , it has been argued that benzodiazepines may not be safe or efficacious beyond 3 months continuous dosage . This study was design ed to provide data regarding efficacy , safety , possible tolerance development , and possible withdrawal effects of administering ketazolam and diazepam for a 6-month period . Chronic anxiety patients were screened for participation according to specific inclusion and exclusion criteria . Of 139 patients , forty-four terminated prematurely for non-drug related reasons and are not included in the analysis . Of the ninety-five patients remaining , sixty-three were on ketazolam , and thirty-two on diazepam . Efficacy parameters included the Hamilton Anxiety Rating Scale , Physician 's Global Impressions , Target Symptoms , Self-Rating Symptom Scale , and Patient 's Global Impressions . Patients were evaluated weekly for the first month except for Week 3 , and then seen bi-weekly and rated monthly . The results of the study showed that ketazolam was as efficacious as diazepam in treating anxiety and result ed in fewer side-effects . No adverse effects were noted in either group . Both benzodiazepines were safe and well-tolerated . No tolerance or withdrawal effects were noted . The average doses were ketazolam Week 4 ( 50.0 mg ) , Week 24 ( 66.14 mg ) and diazepam Week 4 ( 26.33 mg ) and Week 24 ( 33.0 mg ) . An increase in anxiety occurred in a significant number of patients after termination of either drug . By 2 weeks after the last dose many patients were free of anxiety and did not require further treatment . These results demonstrate that benzodiazepines are safe and efficacious for at least 6 months of continuous dosage The authors analyzed the relative contributions of improvement in depressive and anxiety symptoms , as measured by the Hamilton Rating Scale for Depression ( HRSD ) and the Hamilton Rating Scale for Anxiety ( HRSA ) , respectively , after 1 week of treatment to the prediction of improvement in HRSD score after 6 weeks of antidepressant pharmacotherapy . Fifty-six subjects completed 6 weeks of treatment with either desipramine ( n = 20 ) , alprazolam ( n = 18 ) , or a desipramine-alprazolam combination ( n = 18 ) . The results showed that early improvement in the HRSD was a moderately strong predictor of the total 6-week improvement in HRSD score , and a better predictor than early improvement in the HRSA . Partial correlations showed that early HRSD improvement was significantly related to total HRSD improvement within the alprazolam group . This pattern of response differed from those observed for the other treatment groups . Desipramine-treated subjects showed gradual improvement over the course of the study , and the improvement in week 1 was not so strongly predictive of overall improvement . The relationship between early and total HRSD improvement for the combination treatment group was intermediate to the other two groups . These findings are discussed in the context of the relationship between depression and anxiety , and potential implication s for the treatment of these overlapping and often mixed syndromes Forty endogenously depressed patients given st and ard antidepressants and /or electroconvulsive therapy in a general hospital psychiatric ward were assessed using the short form of the Beck Depression Inventory and the Hamilton Depression Rating Scale . The patients were then r and omly assigned to two groups : Under double-blind conditions , one group received in addition 20 mg diazepam per day and the other , identical placebos . No additional benzodiazepines were prescribed during the study . St and ard therapy with tricyclic antidepressants or electric shock was determined by the patients ' own psychiatrists . The assessment s were repeated after ten days of diazepam or placebo treatment . Fourteen patients ( seven in each group ) also completed the Buss-Durkee Hostility Inventory . Results of the Beck Depression Inventory indicated that the addition of diazepam retarded the improvement of the patients receiving only tricyclic antidepressants but had no effect on the recovery of patients receiving electroconvulsive therapy |
13,557 | 31,340,003 | Quantitative studies showed a positive impact of CBKs on reducing the incidence of puerperal sepsis and neonatal tetanus .
The review also identified CBK use to be associated with a reduction in perinatal , neonatal and young infant mortality .
Qualitative studies suggested that a lack of awareness of the importance of CBKs and clean delivery practice s , unavailability of CBKs and financial constraints to purchase CBKs were the potential barriers .
CBKs appear to be a promising strategy to reduce maternal and neonatal morbidity and mortality . | Poor infection control practice s during childbirth are recognised as a critical factor leading to life-threatening maternal and newborn sepsis .
Therefore , this paper assesses the effectiveness of clean birth kits ( CBKs ) to ensure a safe birthing environment . | The potential for traditional birth attendants ( TBAs ) to improve neonatal health outcomes has largely been overlooked during the current debate regarding the role of TBAs in improving maternal health . R and omly-selected TBAs ( n=93 ) were interviewed to gain a more thorough underst and ing of their knowledge , attitudes , and practice s regarding maternal and newborn care . Practice s , such as using a clean cord-cutting instrument ( 89 % ) and h and -washing before delivery ( 74 % ) , were common . Other beneficial practice s , such as thermal care , were low . Trained TBAs were more likely to wash h and s with soap before delivery , use a clean delivery-kit , and advise feeding colostrum . Although mustard oil massage was a universal practice , 52 % of the TBAs indicated their willingness to consider alternative oils . Low-cost , evidence -based interventions for improving neonatal outcomes might be implemented by TBAs in this setting where most births take place in the home and neonatal mortality risk is high . Continuing efforts to define the role of TBAs may benefit from an emphasis on their potential as active promoters of essential newborn care A study was carried out in Misungwi and Kwimba Districts , Tanzania to determine the effectiveness of clean delivery kits in preventing cord infection and puerperal sepsis and to provide qualitative information on community acceptability , correct use , and appropriateness of the kits . This study involved pregnant women aged 18 - 45 years old . In the delivery kit intervention population , the Maternal and Child Health Aide ( MCHA ) assigned to the health facility provided pregnant mothers with a clean delivery kit on their first antenatal visit . She explained how to use each of the kit components , with the aid of pictorial instructions included in the kit . The pregnant mothers were asked to convey the information to whoever assisted them during delivery . The MCHA also gave them health education based on the principles of the " six cleans " recognized by WHO ( i.e. , clean h and s , clean perineum , clean delivery surface , clean cord cutting and tying instruments , clean cutting surface ) . Women received the clean delivery kit free of charge in accordance with the r and omised stepped-wedge design schedule . During the first week following delivery , the Village Health Workers ( VHWs ) from both the intervention and control groups made two visits to the households of mothers who had delivered . They administered question naire about delivery to mother and birth attendant . During the two scheduled postpartum visits , those who were suspected to have puerperal sepsis or cord infection of the baby were referred to the health facility clinician for confirmation . Results indicated that use of clean delivery kit had a positive effect on reducing both cord infection and puerperal sepsis . The use of a clean home delivery kit coupled with an educational intervention about the " six cleans " had a significant effect on reducing the incidence of cord infection and puerperal sepsis among women enrolled in the study . In low re source setting s where home birth is common and clean delivery supplies are scarce , disposable kits can be made available through health clinics , markets , pharmacies or other channels to help reduce rates of infection BACKGROUND There are approximately 4 million neonatal deaths and half a million maternal deaths worldwide each year . There is limited evidence from clinical trials to guide the development of effective maternity services in developing countries . METHODS We performed a cluster-r and omized , controlled trial involving seven subdistricts ( talukas ) of a rural district in Pakistan . In three talukas r and omly assigned to the intervention group , traditional birth attendants were trained and issued disposable delivery kits ; Lady Health Workers linked traditional birth attendants with established services and documented processes and outcomes ; and obstetrical teams provided outreach clinics for antenatal care . Women in the four control talukas received usual care . The primary outcome measures were perinatal and maternal mortality . RESULTS Of the estimated number of eligible women in the seven talukas , 10,114 ( 84.3 percent ) were recruited in the three intervention talukas , and 9443 ( 78.7 percent ) in the four control talukas . In the intervention group , 9184 women ( 90.8 percent ) received antenatal care by trained traditional birth attendants , 1634 women ( 16.2 percent ) were seen antenatally at least once by the obstetrical teams , and 8172 safe-delivery kits were used . As compared with the control talukas , the intervention talukas had a cluster-adjusted odds ratio for perinatal death of 0.70 ( 95 percent confidence interval , 0.59 to 0.82 ) and for maternal mortality of 0.74 ( 95 percent confidence interval , 0.45 to 1.23 ) . CONCLUSIONS Training traditional birth attendants and integrating them into an improved health care system were achievable and effective in reducing perinatal mortality . This model could result in large improvements in perinatal and maternal health in developing countries OBJECTIVE To determine the feasibility and acceptability of providing clean birth kits ( CBKs ) containing misoprostol for self-administration in a rural setting in Papua New Guinea . METHODS A prospect i ve intervention study was conducted between April 8 , 2013 , and October 24 , 2014 . Eligible participants were women in the third trimester of pregnancy who attended a prenatal clinic in Unggai Bena . Participants received individual instruction and were then given a CBK containing 600μg misoprostol tablets for self-administration following an unsupervised birth if they could demonstrate their underst and ing of correct use of items in the CBK . Data regarding the use and acceptability of the CBK and misoprostol were collected during postpartum follow-up . RESULTS Among 200 participants , 106 ( 53.0 % ) had an unsupervised birth , and 99 ( 93.4 % ) of these women used the CBK . All would use the CBK again and would recommend it to others . Among these 99 women , misoprostol was self-administered by 98 ( 99.0 % ) , all of whom would take the drug again and would recommend it to others . CONCLUSION The findings strengthen the case for community-based use of misoprostol to prevent postpartum hemorrhage in remote communities . Large-scale interventions should be planned to further evaluate impact and acceptability |
13,558 | 31,993,558 | The largest benefits result ed from interventions that improved processes , promoted team-based care , and incorporated the use of scribes/medical assistants to complete EHR documentation and tasks .
Implementation of EHR interventions to improve clinical workflows worsened burnout , but EHR improvements had positive effects .
Time interventions had mixed effects on burnout .
The results of our study suggest that organization-directed workplace interventions that improve processes , optimize EHRs , reduce clerical burden by the use of scribes , and implement team-based care can lessen physician burnout .
Benefits of process changes can enhance physician resiliency , augment care provided by the team , and optimize the coordination and communication of patient care and health information | Teamwork involved initiatives to incorporate scribes or medical assistants into electronic health record ( EHR ) processes , exp and team responsibilities , and improve communication among physicians . | CONTEXT Data are sparse on the effect of varying the duration s of internal medicine attending physician ward rotations . OBJECTIVE To compare the effects of 2- vs 4-week inpatient attending physician rotations on unplanned patient revisits , attending evaluations by trainees , and attending propensity for burnout . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized crossover noninferiority trial , with attending physicians as the unit of crossover r and omization and 4-week rotations as the active control , conducted in a US university-affiliated teaching hospital in academic year 2009 . Participants were 62 attending physicians who staffed at least 6 weeks of inpatient service , the 8892 unique patients whom they discharged , and the 147 house staff and 229 medical students who evaluated their performance . INTERVENTION Assignment to r and om sequences of 2- and 4-week rotations . MAIN OUTCOME MEASURES Primary outcome was 30-day unplanned revisits ( visits to the hospital 's emergency department or urgent ambulatory clinic , unplanned readmissions , and direct transfers from neighboring hospitals ) for patients discharged from 2- vs 4-week within-attending-physician rotations . Noninferiority margin was a 2 % increase ( odds ratio [ OR ] of 1.13 ) in 30-day unplanned patient revisits . Secondary outcomes were length of stay ; trainee evaluations of attending physicians ; and attending physician reports of burnout , stress , and workplace control . RESULTS Among the 8892 patients , there were 2437 unplanned revisits . The percentage of 30-day unplanned revisits for patients of attending physicians on 2-week rotations was 21.2 % compared with 21.5 % for 4-week rotations ( mean difference , -0.3 % ; 95 % CI , -1.8 % to + 1.2 % ) . The adjusted OR of a patient having a 30-day unplanned revisit after 2- vs 4-week rotations was 0.97 ( 1-sided 97.5 % upper confidence limit , 1.07 ; noninferiority P = .007 ) . Average length of stay was not significantly different ( geometric means for 2- vs 4-week rotations were 67.2 vs 67.5 hours ; difference , -0.9 % ; 95 % CI , -4.7 % to + 2.9 % ) . Attending physicians were more likely to score lower in their ability to evaluate trainees after 2- vs 4-week rotations by both house staff ( 41 % vs 28 % rated less than perfect ; adjusted OR , 2.10 ; 95 % CI , 1.50 - 3.02 ) and medical students ( 82 % vs 69 % rated less than perfect ; adjusted OR , 1.41 ; 95 % CI , 1.06 - 2.10 ) . They were less likely to report higher scores of both burnout severity ( 16 % vs 35 % ; adjusted OR , 0.39 ; 95 % CI , 0.26 - 0.58 ) and emotional exhaustion ( 19 % vs 37 % ; adjusted OR , 0.45 ; 95 % CI , 0.31 to 0.64 ) after 2- vs 4-week rotations . CONCLUSIONS The use of 2-week inpatient attending physician rotations compared with 4-week rotations did not result in an increase in unplanned patient revisits . It was associated with better self-rated measures of attending physician burnout and emotional exhaustion but worse evaluations by trainees . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00930111 Background : Shorter resident duty periods are increasingly m and ated to improve patient safety and physician well-being . However , increases in continuity-related errors may counteract the purported benefits of reducing fatigue . We evaluated the effects of 3 resident schedules in the intensive care unit ( ICU ) on patient safety , resident well-being and continuity of care . Methods : Residents in 2 university-affiliated ICUs were r and omly assigned ( in 2-month rotation-blocks from January to June 2009 ) to in-house overnight schedules of 24 , 16 or 12 hours . The primary patient outcome was adverse events . The primary resident outcome was sleepiness , measured by the 7-point Stanford Sleepiness Scale . Secondary outcomes were patient deaths , preventable adverse events , and residents ’ physical symptoms and burnout . Continuity of care and perceptions of ICU staff were also assessed . Results : We evaluated 47 ( 96 % ) of 49 residents , all 971 admissions , 5894 patient-days and 452 staff surveys . We found no effect of schedule ( 24- , 16- or 12-h shifts ) on adverse events ( 81.3 , 76.3 and 78.2 events per 1000 patient-days , respectively ; p = 0.7 ) or on residents ’ sleepiness in the daytime ( mean rating 2.33 , 2.61 and 2.30 , respectively ; p = 0.3 ) or at night ( mean rating 3.06 , 2.73 and 2.42 , respectively ; p = 0.2 ) . Seven of 8 preventable adverse events occurred with the 12-hour schedule ( p = 0.1 ) . Mortality rates were similar for the 3 schedules . Residents ’ somatic symptoms were more severe and more frequent with the 24-hour schedule ( p = 0.04 ) ; however , burnout was similar across the groups . ICU staff rated residents ’ knowledge and decision-making worst with the 16-hour schedule . Interpretation : Our findings do not support the purported advantages of shorter duty schedules . They also highlight the trade-offs between residents ’ symptoms and multiple secondary measures of patient safety . Further delineation of this emerging signal is required before widespread system change . Trial registration : Clinical Trials.gov , no. NCT00679809 PURPOSE The increasing use of electronic medical records during the clinical encounter brings not only benefits but also barriers that may affect the doctor-patient relationship and increase the work burden of the physician . We evaluated whether the use of an electronic medical record scribe in an academic urology program would ameliorate these problems . MATERIAL S AND METHODS We r and omly assigned electronic medical record scribes to the office hours of 5 academic urologists , and using surveys we evaluated patient and physician acceptance and satisfaction . RESULTS Patients were accepting of an electronic medical record scribe and satisfaction rates were high ( 93 % vs 87 % in the absence of a scribe , p = 0.36 ) . Patients were comfortable disclosing urological information in the presence of the scribe . Physicians were dramatically more satisfied with office hours when a scribe was present ( 69 % vs 19 % , p < 0.001 ) . We were unable to determine whether the presence of a scribe improves productivity . CONCLUSIONS Electronic medical record scribes in a urology practice may be a practical solution to provide documentation while maintaining or improving the doctor-patient relationship because they increase physician satisfaction and do not detract from patient satisfaction OBJECTIVE . To mitigate the risks of fatigue-related medical errors , the Accreditation Council for Graduate Medical Education introduced work hour limits for resident physicians in 2003 . Our goal was to determine whether work hours , sleep , and safety changed after implementation of the Accreditation Council for Graduate Medical Education st and ards . METHODS . We conducted a prospect i ve cohort study in which residents from 3 large pediatric training programs provided daily reports of work hours and sleep . In addition , they completed reports of near-miss and actual motor vehicle crashes , occupational exposures , self-reported medical errors , and ratings of educational experience . They were screened for depression and burnout . Concurrently , at 2 of the centers , data on medication errors were collected prospect ively by using an established active surveillance method . RESULTS . A total of 220 residents provided 6007 daily reports of their work hours and sleep , and 16 158 medication orders were review ed . Although scheduling changes were made in each program to accommo date the st and ards , 24- to 30-hour shifts remained common , and the frequency of residents ’ call remained largely unchanged . There was no change in residents ’ measured total work hours or sleep hours . There was no change in the overall rate of medication errors , and there was a borderline increase in the rate of resident physician ordering errors , from 1.06 to 1.38 errors per 100 patient-days . Rates of motor vehicle crashes , occupational exposures , depression , and self-reported medical errors and overall ratings of work and educational experiences did not change . The mean length of extended- duration ( on-call ) shifts decreased 2.7 % to 28.5 hours , and rates of resident burnout decreased significantly ( from 75.4 % to 57.0 % ) . CONCLUSIONS . Total hours of work and sleep did not change after implementation of the duty hour st and ards . Although fewer residents were burned out , rates of medication errors , resident depression , and resident injuries and educational ratings did not improve RATIONALE Around-the-clock intensivist presence in intensive care units ( ICUs ) has been promoted as necessary to optimize outcomes . Little data have addressed how it affects the multiple stakeholders in such care . OBJECTIVES To assess effects of around-the-clock intensivist presence on intensivists , patients , families , housestaff , and nurses . METHODS This 32-week , crossover pilot trial of two intensivist staffing models , performed in two Canadian ICUs , alternated 8-week blocks of two staffing models : the st and ard model , where one intensivist worked for 7 days , taking night call from home ; and the shift work model , where one intensivist worked 7 day shifts , while other intensivists remained in the ICU at night . MEASUREMENTS AND MAIN RESULTS Surveys scaled from 0 - 100 points assessed outcomes for 24 intensivists ( primary outcome : burnout ) ; 119 families ( satisfaction ) ; 74 nurses ( satisfaction with collaboration and communications , role conflict ) ; and 34 housestaff ( autonomy , supervision , and learning opportunities ) . Outcomes for 501 patients included mortality , length of stay , and re source use . Intensivists doing shift work experienced less burnout ( -6.9 points ; P = 0.04 ) . Adjusted hospital mortality ( odds ratio , 1.22 ; P = 0.44 ) , ICU length of stay ( -6 h ; P = 0.46 ) , and family satisfaction ( 0.9 points ; P = 0.79 ) did not differ between staffing models . Under shift work staffing , nurses reported more role conflict ( 9 points ; P < 0.001 ) , whereas nighttime housestaff reported less autonomy , more supervision , but no difference in learning opportunities . CONCLUSIONS Shiftwork staffing was better for intensivists and most were receptive once they had experienced it . Although there were no evident negative outcomes for patients or families , further evaluation is needed to clarify how around-the-clock intensivist staffing influences the various stakeholders in ICU care , given power considerations in this study . Clinical trial registered with www . clinical trials.gov ( NCT 01146691 ) Background Use of electronic health records ( EHRs ) is associated with physician stress and burnout . While emergency departments and subspecialists have used scribes to address this issue , little is known about the impact of scribes in academic primary care . Objective Assess the impact of a scribe on physician and patient satisfaction at an academic general internal medicine ( GIM ) clinic . Design Prospect i ve , pre-post-pilot study . During the 3-month pilot , physicians had clinic sessions with and without a scribe . We assessed changes in ( 1 ) physician workplace satisfaction and burnout , ( 2 ) time spent on EHR documentation , and ( 3 ) patient satisfaction . Participants Six GIM faculty and a convenience sample of their patients ( N = 325 ) at an academic GIM clinic . Main Measures A 21-item pre- and 44-item post-pilot survey assessed physician workplace satisfaction and burnout . Physicians used logs to record time spent on EHR documentation outside of clinic hours . A 27-item post-visit survey assessed patient satisfaction during visits with and without the scribe . Key Results Of six physicians , 100 % were satisfied with clinic workflow post-pilot ( vs. 33 % pre-pilot ) , and 83 % were satisfied with EHR use post-pilot ( vs. 17 % pre-pilot ) . Physician burnout was low at baseline and did not change post-pilot . Mean time spent on post-clinic EHR documentation decreased from 1.65 to 0.76 h per clinic session ( p = 0.02 ) . Patient satisfaction was not different between patients who had clinic visits with vs. without scribe overall or by age , gender , and race . Compared to patients 65 years or older , younger patients were more likely to report that the physician was more attentive and provided more education during visits with the scribe present ( p = 0.03 and 0.02 , respectively ) . Male patients were more likely to report that they disliked having a scribe ( p = 0.03 ) . Conclusion In an academic GIM setting , employment of a scribe was associated with improved physician satisfaction without compromising patient satisfaction PURPOSE Comprehensiveness is lauded as 1 of the 5 core virtues of primary care , but its relationship with outcomes is unclear . We measured associations between variations in comprehensiveness of practice among family physicians and healthcare utilization and costs for their Medicare beneficiaries . METHODS We merged data from 2011 Medicare Part A and B cl aims files for a complex r and om sample of family physicians engaged in direct patient care , including 100 % of their cl aim ed care of Medicare beneficiaries , with data reported by the same physicians during their participation in Maintenance of Certification for Family Physicians ( MC-FP ) between the years 2007 and 2011 . We created a measure of comprehensiveness from m and atory self-reported survey items as part of MC-FP examination registration . We compared this measure to another derived from Medicare ’s Berenson-Eggers Type of Service ( BETOS ) codes . We then examined the association between the 2 measures of comprehensiveness and hospitalizations , Part B payments , and combined Part A and B payments . RESULTS Our full family physician sample consists of 3,652 physicians providing the plurality of care to 555,165 Medicare beneficiaries . Of these , 1,133 recertified between 2007 and 2011 and cared for 185,044 beneficiaries . There was a modest correlation ( 0.30 ) between the BETOS and self-reported comprehensiveness measures . After adjusting for beneficiary and physician characteristics , increasing comprehensiveness was associated with lower total Medicare Part A and B costs and Part B costs alone , but not with hospitalizations ; the association with spending was stronger for the BETOS measure than for the self-reported measure ; higher BETOS scores significantly reduced the likelihood of a hospitalization . CONCLUSIONS Increasing family physician comprehensiveness of care , especially as measured by cl aims measures , is associated with decreasing Medicare costs and hospitalizations . Payment and practice policies that enhance primary care comprehensiveness may help “ bend the cost curve . ABSTRACT BACKGROUND Work conditions in primary care are associated with physician burnout and lower quality of care . OBJECTIVE We aim ed to assess if improvements in work conditions improve clinician stress and burnout . SUBJECTS Primary care clinicians at 34 clinics in the upper Midwest and New York City participated in the study . STUDY DESIGN This was a cluster r and omized controlled trial . MEASURES Work conditions , such as time pressure , workplace chaos , and work control , as well as clinician outcomes , were measured at baseline and at 12–18 months . A brief worklife and work conditions summary measure was provided to staff and clinicians at intervention sites . INTERVENTIONS Diverse interventions were grouped into three categories : 1 ) improved communication ; 2 ) changes in workflow , and 3 ) targeted quality improvement ( QI ) projects . ANALYSIS Multilevel regressions assessed impact of worklife data and interventions on clinician outcomes . A multilevel analysis then looked at clinicians whose outcome scores improved and determined types of interventions associated with improvement . RESULTS Of 166 clinicians , 135 ( 81.3 % ) completed the study . While there was no group treatment effect of baseline data on clinician outcomes , more intervention clinicians showed improvements in burnout ( 21.8 % vs 7.1 % less burned out , p = 0.01 ) and satisfaction ( 23.1 % vs 10.0 % more satisfied , p = 0.04 ) . Burnout was more likely to improve with workflow interventions [ Odds Ratio ( OR ) of improvement in burnout 5.9 , p = 0.02 ] , and with targeted QI projects than in controls ( OR 4.8 , p = 0.02 ) . Interventions in communication or workflow led to greater improvements in clinician satisfaction ( OR 3.1 , p = 0.04 ) , and showed a trend toward greater improvement in intention to leave ( OR 4.2 , p = 0.06 ) . LIMITATIONS We used heterogeneous intervention types , and were uncertain how well interventions were instituted . CONCLUSIONS Organizations may be able to improve burnout , dissatisfaction and retention by addressing communication and workflow , and initiating QI projects targeting clinician concerns RATIONALE Little is known about the consequences of intensivists ’ work schedules , or intensivist continuity of care . OBJECTIVES To assess the impact of weekend respite for intensivists , with consequent reduction in continuity of care , on them and their patients . METHODS In five medical intensive care units ( ICUs ) in four academic hospitals we performed a prospect i ve , cluster-r and omized , alternating trial of two intensivist staffing schedules . Daily coverage by a single intensivist in half-month rotations ( continuous schedule ) was compared with weekday coverage by a single intensivist , with weekend cross-coverage by colleagues ( interrupted schedule ) . We studied consecutive patients admitted to study units , and the intensivists working in four of the participating units . MEASUREMENTS AND MAIN RESULTS The primary patient outcome was ICU length of stay (LOS);we also assessed hospital LOS and mortality rates . The primary intensivist outcome was physician burnout . Analysis was by multivariable regression . A total of 45 intensivists and 1,900 patients participated in the study . Continuity of care differed between schedules ( patients with multiple intensivists = 28 % under continuous schedule vs. 62 % under interrupted scheduling ; P < 0.0001 ) . LOS and mortality were nonsignificantly higher under continuous scheduling ( ΔICU LOS 0.36 d , P = 0.20 ; Δhospital LOS 0.34 d , P = 0.71 ; ICU mortality , odds ratio = 1.43 , P = 0.12 ; hospital mortality , odds ratio = 1.17,P = 0.41 ) . Intensivists experienced significantly higher burnout , work – home life imbalance , and job distress working under the continuous schedule . CONCLUSIONS Work schedules where intensivists received weekend breaks were better for the physicians and , despite lower continuity of intensivist care , did not worsen outcomes for medical ICU patients BACKGROUND Patient safety and sleep experts advocate a protected sleep period for residents . OBJECTIVE We examined whether interns scheduled for a protected sleep period during overnight call would have better end-of-rotation assessment s of burnout , depression , and empathy scores compared with interns without protected sleep periods and whether the amount of sleep obtained during on call predicted end-of-rotation assessment s. METHODS We conducted a r and omized , controlled trial with internal medicine interns at the Philadelphia Veterans Affairs Medical Center ( PVAMC ) and the Hospital of the University of Pennsylvania ( HUP ) in academic year 2009 - 2010 . Four-week blocks were r and omly assigned to either overnight call permitted under the 2003 duty hour st and ards or a protected sleep period from 12:30 am to 5:30 am . Participants wore wrist actigraphs . At the beginning and end of the rotations , they completed the Beck Depression Inventory ( BDI-II ) , Maslach Burnout Inventory ( MBI-HSS ) , and Interpersonal Reactivity Index ( IRI ) . RESULTS A total of 106 interns participated . There were no significant differences between groups in end-of-rotation BDI-II , MBI-HSS , or IRI scores at either location ( P > .05 ) . Amount of sleep while on call significantly predicted lower MBI-Emotional Exhaustion ( P < .003 ) , MBI-Depersonalization ( P < .003 ) , and IRI-Personal Distress ( P < .006 ) at PVAMC , and higher IRI-Perspective Taking ( P < .008 ) at HUP . CONCLUSIONS A protected sleep period produced few consistent improvements in depression , burnout , or empathy , although depression was already low at baseline . Possibly the amount of protected time was too small to affect these emotional states or sleep may not be directly related to these scores Background Concern persists that inflexible duty‐hour rules in medical residency programs may adversely affect the training of physicians . Methods We r and omly assigned 63 internal medicine residency programs in the United States to be governed by st and ard duty‐hour policies of the 2011 Accreditation Council for Graduate Medical Education ( ACGME ) or by more flexible policies that did not specify limits on shift length or m and atory time off between shifts . Measures of educational experience included observations of the activities of interns ( first‐year residents ) , surveys of trainees ( both interns and residents ) and faculty , and intern examination scores . Results There were no significant between‐group differences in the mean percentages of time that interns spent in direct patient care and education nor in trainees ' perceptions of an appropriate balance between clinical dem and s and education ( primary outcome for trainee satisfaction with education ; response rate , 91 % ) or in the assessment s by program directors and faculty of whether trainees ' workload exceeded their capacity ( primary outcome for faculty satisfaction with education ; response rate , 90 % ) . Another survey of interns ( response rate , 49 % ) revealed that those in flexible programs were more likely to report dissatisfaction with multiple aspects of training , including educational quality ( odds ratio , 1.67 ; 95 % confidence interval [ CI ] , 1.02 to 2.73 ) and overall well‐being ( odds ratio , 2.47 ; 95 % CI , 1.67 to 3.65 ) . In contrast , directors of flexible programs were less likely to report dissatisfaction with multiple educational processes , including time for bedside teaching ( response rate , 98 % ; odds ratio , 0.13 ; 95 % CI , 0.03 to 0.49 ) . Average scores ( percent correct answers ) on in‐training examinations were 68.9 % in flexible programs and 69.4 % in st and ard programs ; the difference did not meet the noninferiority margin of 2 percentage points ( difference , ‐0.43 ; 95 % CI , ‐2.38 to 1.52 ; P=0.06 for noninferiority ) . Conclusions There was no significant difference in the proportion of time that medical interns spent on direct patient care and education between programs with st and ard duty‐hour policies and programs with more flexible policies . Interns in flexible programs were less satisfied with their educational experience than were their peers in st and ard programs , but program directors were more satisfied . ( Funded by the National Heart , Lung , and Blood Institute and the ACGME ; iCOMPARE Clinical Trials.gov number , NCT02274818 . Background While primary care work conditions are associated with adverse clinician outcomes , little is known about the effect of work condition interventions on quality or safety . Design A cluster r and omized controlled trial of 34 clinics in the upper Midwest and New York City . Participants Primary care clinicians and their diabetic and hypertensive patients . Interventions Quality improvement projects to improve communication between providers , workflow design , and chronic disease management . Intervention clinics received brief summaries of their clinician and patient outcome data at baseline . Main Measures We measured work conditions and clinician and patient outcomes both at baseline and 6–12 months post-intervention . Multilevel regression analyses assessed the impact of work condition changes on outcomes . Subgroup analyses assessed impact by intervention category . Key Results There were no significant differences in error reduction ( 19 % vs. 11 % , OR of improvement 1.84 , 95 % CI 0.70 , 4.82 , p = 0.21 ) or quality of care improvement ( 19 % improved vs. 44 % , OR 0.62 , 95 % CI 0.58 , 1.21 , p = 0.42 ) between intervention and control clinics . The conceptual model linking work conditions , provider outcomes , and error reduction showed significant relationships between work conditions and provider outcomes ( p ≤ 0.001 ) and a trend toward a reduced error rate in providers with lower burnout ( OR 1.44 , 95 % CI 0.94 , 2.23 , p = 0.09 ) . Limitations Few quality metrics , short time span , fewer clinicians recruited than anticipated . Conclusions Work-life interventions improving clinician satisfaction and well-being do not necessarily reduce errors or improve quality . Longer , more focused interventions may be needed to produce meaningful improvements in patient care . Clinical trial registration number : Clinical Trials.gov # NCT02542995 |
13,559 | 32,374,780 | Conclusion None of the litter treatments influenced the feed intake of broilers .
Meta-analyses of the selected studies showed positive and significant effects of the litter treatments on broiler performance and litter quality when compared with controls .
Alkalizing was associated with worse feed conversion and high mortality of broilers | Objective The choice of the most suitable litter treatment should be based on scientific evidence .
This systematic review assessed the effectiveness of litter treatments on ammonia concentration , pH , moisture and pathogenic microbiota of the litter and their effects on body weight , feed intake , feed conversion and mortality of broilers . | Objective High NH3 emissions from poultry houses are reported to have negative impacts on health , welfare and safety of birds and humans , and on the environment . Objective of the present study was to determine the effects of two litter amendments on the NH3 levels in broiler closed houses under hot-humid conditions . Methods Giving a completely r and omize design , nine closed houses , each housed 32,500 birds on paddy husk litter , were r and omly allocated into two treatment ( Mizuho ; a bacterial culture mix and Rydall OE ; an enzymatic biocatalyst ) and control groups . NH3 levels were determined thrice a day ( 0600 , 1200 , and 1800 h ) , at three heights from the litter surface ( 30 , 90 , and 150 cm ) , at 20 predetermined locations of a house , from day 1 to 41 . Results Rydall significantly reduced the NH3 level compared to control and Mizuho . NH3 levels at 30 cm were significantly higher than that of 90 and 150 cm . The NH3 levels at 30 cm height were higher than 25 ppm level from day 9 , 11 , and 13 in Mizuho , control , and Rydall groups , respectively to day 41 . NH3 levels at 150 cm height were higher than maximum threshold limit of 50 ppm for human exposure from day 12 , 14 , and 15 in Mizuho , control , and Rydall groups , respectively to day 33 . Being significantly different among each other , the NH3 level was highest and lowest at 0600 and 1800 h. Litter amendments had no significant effects on growth performance . Rydall significantly increased the litter N content on day 24 . Conclusion It was concluded that the NH3 levels of closed house broiler production facilities under tropical condition are so high that both birds and workers are exposed to above recommended levels during many days of the growing period . Compared to microbial culture , the enzymatic biocatalyst was found to be more effective in reducing NH3 level Two commercially available litter treatments , aluminum sulfate and sodium bisulfate , were tested to determine their effect on Campylobacter and Salmonella levels associated with commercial broilers during a 6-wk grow-out period . A total of 20 broiler houses at 10 different locations were studied ; 5 aluminum sulfate-treated houses , 5 sodium bisulfate-treated houses , and 10 paired , untreated control houses . A single application rate was investigated for each treatment . Fecal sample s ( n=20 per house ) were analyzed at wk 2 , 4 , and 5 and 6 for Campylobacter and Salmonella . The results indicated that , at the application rates investigated , both acidifying litter treatments caused a slight delay in the onset of Campylobacter colonization in broiler chicks . Salmonella levels remained unaffected , with no significant effect seen with either treatment ( P > 0.05 ) . Campylobacter population s and Salmonella incidence associated with unprocessed , whole-carcass rinse sample s ( n=10 per house ) analyzed at the end of production ( wk 5 and 6 ) were unaffected by treatment The survival of Salmonella Typhimurium LT2 in r and omly packed beds of glass beads , microporous silica particles and Sephadex microspheres is examined . It is shown that the decrease in the percentage cell recovery in these porous material s at reduced water content is not correlated with the global water activity as determined by conventional vapour pressure measurements but rather with the osmotic shock induced by the sudden redistribution of water and air among the microscopic pores in the matrix surrounding the cells . For this reason the bacterial survival and growth data correlates best with physical measurements , such as NMR and electrical conductivity , which are sensitive to the microscopic air-water distribution . The implication s of this observation in food safety and preservation are discussed ABSTRACT The litter quality is an important factor affecting the performance , welfare and carcass quality of the broilers . Depending on the progress of the fattening duration , some material s may be added to the litter in order to keep the pH , moisture and ammonia levels in the litter under control . Sepiolite is a natural material and it has strong absorbing ability to the water . Therefore , the aim of this study was to determine the effects of sepiolite additions to different litter material s on performance and some welfare parameters of broilers and litter characteristics . A total of 288 1‐d‐old male broiler chicks ( ROSS‐308 ) were used . Birds were r and omly allocated to 2 litters ( wood shavings and rice hull ) and 3 sepiolite groups ( 0 , 25 , 50 % ) with 6 replication , and each pen contains 8 chicks . Fattening performance , IgG , tonic immobility period , feather score , skin injures , breast burns , and footpad burns of broilers were not affected significantly by sepiolite additions to the litter . However , sepiolite addition to the litter can improve litter quality . There was no significant difference between 2 litter material s because both have same color . There were no significant interactions in examined parameters . In conclusion , addition of sepiolite at 25 and 50 % levels to litter material s may be used as a litter material in the broiler production without adverse welfare and performance problem |
13,560 | 20,190,185 | The presence ( vs the absence ) of metastases of 2 mm or less in diameter in axillary lymph nodes detected on single-section examination was associated with poorer disease-free and overall survival | BACKGROUND The prognostic relevance of isolated tumor cells and micrometastases in lymph nodes from patients with breast cancer has become a major issue since the introduction of the sentinel lymph node procedure .
We conducted a systematic review of this issue . | Pathologists are under increasing pressure to su bmi t fresh tissue for ancillary studies and research protocol s. In several tumor types ( breast , lung , melanoma , colorectal , prostate ) , increased interest in detecting su bmi croscopic nodal metastases through reverse transcriptase polymerase chain reaction analysis of mRNA from portions of lymph nodes has precluded histologic analysis of the entire node for metastases . A retrospective review was undertaken of 227 breast cancer patients prospect ively entered on a research protocol examining the usefulness of sentinel lymph node surgery . All of the patients ultimately underwent complete lymph node dissection . The research protocol required that all nodes greater than 8 mm in size be bisected and su bmi tted separately . Positive lymph nodes were evaluated for unilateral or bilateral involvement in the node sections . Sixty node-positive patients were identified , yielding 230 positive nodes . One hundred seven of these nodes were confirmed to have been bisected . Carcinoma was identified in both lymph node sections in 64 ( 59.8 % ) nodes and in only one-half of the bisected lymph node in 43 ( 40.2 % ) nodes . Involvement of both sections was more likely when patients had multiple nodes positive . In 12 patients , involvement of one-half of the bisected nodes was the only evidence of metastatic disease ( 20.0 % of node-positive patients ) . This evidence suggests that su bmi ssion of less than the complete lymph node for histologic evaluation of metastatic disease decreases the accuracy of lymph node staging . Furthermore , a significant proportion of patients may be erroneously classified as histologically node negative Background Internationally , there is no consensus on the pathology protocol to be used to examine the sentinel lymph node ( SN ) . At present , therefore , various hospitals use different SN pathology protocol s of which the effect has not been fully eluci date d. We hypothesized that differences between hospitals in SN pathology protocol s affect subsequent surgical treatment strategies . Methods Patients from four hospitals ( A – D ) were prospect ively registered when they underwent an SN biopsy . In hospitals A , B , and C , three levels of the SN were examined pathologically , whereas in hospital D , at least seven additional levels were examined . In the absence of apparent metastases with hematoxylin and eosin examination , immunohistochemical examination was performed in all four hospitals . Results In total , 541 eligible patients were included . In hospital D , more patients were diagnosed with a positive SN ( P < .001 ) as compared with hospitals A , B , and C , mainly because of increased detection of isolated tumor cells . This led to more completion axillary lymph node dissections in hospital D ( 66.3 % of patients ( P < .0001 ) , compared with 29.0 % in hospitals A , B , and C combined ) . Positive non-SNs were detected in 13.9 % of patients in hospital D , compared with 9.7 % in hospitals A , B , and C ( P = .70 ) . That is , in 52.4 % of patients in hospital D , a negative completion axillary lymph node dissection was performed , compared with 19.3 % of patients in hospitals A , B , and C combined . Conclusions Differences in SN pathology protocol s between hospitals do have a substantial effect on SN findings and subsequent surgical treatment strategies . Whether ultrastaging and , thus , additional surgery can offer better survival remains to be determined PURPOSE To develop a guideline for the use of sentinel node biopsy ( SNB ) in early stage breast cancer . METHODS An American Society of Clinical Oncology ( ASCO ) Expert Panel conducted a systematic review of the literature available through February 2004 on the use of SNB in early-stage breast cancer . The panel developed a guideline for clinicians and patients regarding the appropriate use of a sentinel lymph node identification and sampling procedure from hereon referred to as SNB . The guideline was review ed by selected experts in the field and the ASCO Health Services Committee and was approved by the ASCO Board of Directors . RESULTS The literature review identified one published prospect i ve r and omized controlled trial in which SNB was compared with axillary lymph node dissection ( ALND ) , four limited meta-analyses , and 69 published single-institution and multicenter trials in which the test performance of SNB was evaluated with respect to the results of ALND ( completion axillary dissection ) . There are currently no data on the effect of SLN biopsy on long-term survival of patients with breast cancer . However , a review of the available evidence demonstrates that , when performed by experienced clinicians , SNB appears to be a safe and acceptably accurate method for identifying early-stage breast cancer without involvement of the axillary lymph nodes . CONCLUSION SNB is an appropriate initial alternative to routine staging ALND for patients with early-stage breast cancer with clinical ly negative axillary nodes . Completion ALND remains st and ard treatment for patients with axillary metastases identified on SNB . Appropriately identified patients with negative results of SNB , when done under the direction of an experienced surgeon , need not have completion ALND . Isolated cancer cells detected by pathologic examination of the SLN with use of specialized techniques are currently of unknown clinical significance . Although such specialized techniques are often used , they are not a required part of SLN evaluation for breast cancer at this time . Data suggest that SNB is associated with less morbidity than ALND , but the comparative effects of these two approaches on tumor recurrence or patient survival are unknown Background Routine axillary lymph node dissection ( ALND ) after selective sentinel lymphadenectomy ( SSL ) in the treatment of breast cancer remains controversial . We sought to determine the need for routine ALND by exploring the relationship between sentinel lymph node ( SLN ) and non-SLN ( NSLN ) status . We also report our experience with disease relapse in the era of SSL and attempt to correlate this with SLN tumor burden . Methods This was a retrospective study of 390 patients with invasive breast cancer treated at a single institution who underwent successful SSL from November 1997 to November 2002 . Results Of the 390 patients , 115 received both SSL and ALND . The percentage of additional positive NSLNs in the SLN-positive group ( 34.2 % ) was significantly higher than in the SLN-negative group ( 5.1 % ; P = .0004 ) . The SLN macrometastasis group had a significantly higher rate of positive NSLNs ( 39.7 % ) compared with the SLN-negative group ( 5.1 % ; P = .0001 ) . Sixteen patients developed recurrences during follow-up , including 6.1 % of SLN-positive and 3.3 % of SLN-negative patients . Among the SLN macrometastasis group , 8.7 % had recurrence , compared with 2.2 % of SLN micrometastases over a median follow-up period of 31.1 months . One regional failure developed out of 38 SLN-positive patients who did not undergo ALND . Conclusions ALND is recommended for patients with SLN macrometastasis because of a significantly higher incidence of positive NSLNs . Higher recurrence rates are also seen in these patients . However , the role of routine ALND in patients with a low SLN tumor burden remains to be further determined by prospect i ve r and omized trials BACKGROUND Examination was performed on pathologic material from patients enrolled in the National Surgical Adjuvant Breast Project ( NSABP ) protocol B-18 , in which the clinical effects of preoperative ( preop ) and postoperative ( postop ) doxorubicin and cyclophosphamide ( AC ) were compared . METHODS Of the total number of 1523 patients , 1234 patients ( 81 % ) were in the pathologically evaluable cohort . Six hundred twenty-six patients had been r and omized prospect ively to receive AC postop and 608 had been r and omized to receive AC preop . Preentry diagnosis was made by fine-needle aspiration ( FNA ) and /or Tru-cut biopsy ( TC ) . AC-induced and other pathologic changes were identified , and their relation to pathologic response and overall survival ( OS ) and disease-free survival ( DFS ) was determined . Frequencies of the number of lymph node metastases , their size , stromal reaction , and extracapsular extension ( ECE ) were compared in the two treatment groups , as was their correlation with OS and DFS . Survival estimates were based on 9 years of follow-up . RESULTS Approximately 13 % of primary breast carcinoma cases exhibited both a clinical complete response ( cCR ) and a pathologic complete response ( absence of invasive tumor [ pCR ] ) to preop AC . An additional 7 % of patients exhibited a pCR in the absence of a cCR . A pCR occurred in 38 % of those patients determined to have achieved a cCR . Poor nuclear grade of the tumor cells in the pre-entry FNA and /or TC specimens significantly predicted a pCR . Patients with the latter exhibited a better OS and DFS compared with those with a pathologic partial response ( presence of sparse invasive tumor [ pPR ] ) or no pathologic response ( pNR ) . Epithelial alterations considered to be induced in tumors by preop AC were comprised of types 1 and 2 giant cells with meganuclei , apocrine metaplasia , and cytoplasmic vacuolation . They had a high degree of specificity ( range , 86 - 99 % ) but a low sensitivity ( range , 7 - 38 % ) . All were predictive of a pPR and were found to be related adversely to OS and DFS . A fibrous stromal reaction noted in tumors or their putative sites in the preop group was found to have only modest degrees of specificity ( 63 % ) and sensitivity ( 74 % ) . Moderate/marked sclerosis of basement membranes of the ductal and ductular elements of the terminal ductolobular unit ( TDLU ) was significantly more frequent in nontumor-bearing areas of breasts from patients in the preop treatment group compared with those in the postop treatment group ( 67 % vs. 48 % ; P < 0.0001 ) . The degrees of change in the TDLU in patients in the postop treatment group were found to be unrelated to age . Lymphatic tumor extension in the primary tumor , as well as a positive lymph node status , were less frequent in the preop treatment group compared with the postop treatment group . The OS and DFS were nearly identical in both treatment groups , being 69 % and 55 % and 70 % and 53 % in the preop and postop treatment groups , respectively , at 9 years . A fibrous stromal response to lymph node metastases was found to be significant for DFS but not OS . ECE was similar in both groups ( 55 % vs. 48 % ; P = 0.12 ) . Only 1 % of ECE was found to be related to axillary failure in both treatment arms combined . There was no significant difference with regard to the parameters of survival for patients in the postop treatment group whose lymph nodes contained micrometastases ( < 2.0 mm ) or mini micrometastases ( < 1.0 mm ) ( the latter detected immunohistochemically with anticytokeratin ) , and a true-negative lymph node status ( not immunohistochemically converted to positive ) . Conversely , there was no apparent difference with regard to OS in preop treated patients with lymph node micrometastases , mini micrometastases , and macrometastases ( P = 0.19 ) . Those with mini micrometastases had a significantly worse OS compared with those with a true-negative lymph node status ( P = 0.0007 ) . DFS remained worse for patients in that treatment group with micrometastases and mini micrometastases compared with those with negative lymph nodes , although it was better than that for patients with macrometastases ( P = 0.02 ) . CONCLUSIONS Poor nuclear grade of tumor cells in the preentry FNA or TC specimens in the preop group was predictive of a pCR . AC-induced meganuclear giant cells and apocrine changes and nuclear and histologic grade s of the primary tumors also were found to be prognostically significant in patients in the preop treatment group , and the latter two variables were found to be significant for those patients in the postop treatment group . No evidence was found to support the need for axillary lymph node radiation for ECE of lymph node metastases . Extended pathologic or immunohistochemical procedures also appear to be unnecessary for the detection of lymph node mini micrometastases , at least when traditional postop chemotherapy is used . The adverse relation between such small metastases and OS and DFS after preop AC appears to be related to the timing of the chemotherapy administration rather than any pathobiologic reasons The current findings completely affirm the validity of our original observations indicating the appropriateness of grouping primary breast cancer patients into those with negative , 1 to 3 , or ≫4 positive nodes . Results , however , reveal that there is a risk in combining all patients with ≫4 positive nodes into a single group . Since there was a 25 % greater disease‐free survival and an 18 % greater survival in those with 4 to 6 than in those with ≫13 positive axillary nodes , such a unification may provide misleading information regarding patient prognosis , as well as the worth of a therapeutic regimen when compared with another from a putatively similar patient population . Of particular interest were findings relating the conditional probability , i.e. , the hazard rate , of a treatment failure or death each year during the 5‐year period following operation to nodal involvement with tumor . Whereas the hazard rate for those with negative , or 1 to 3 positive nodes , was relatively low and constant , in those with ≫4 positive nodes the risk in the early years was much greater , but by the fifth year it was similar to that occurring when 1‐3 nodes were involved , and not much different from negative node patients . The same pattern existed whether 4 to 6 or ≫13 nodes were positive . When the current findings are considered relative to other factors with predictive import , it is concluded that nodal status still remains the primary prognostic discriminant |
13,561 | 28,647,158 | There was no statistically significant difference in visual analog scale , vertebral height , kyphotic angular , and quality of life .
The main operative complications were bone cement leakage and adjacent vertebral fracture , without difference between the two groups .
In view of the current evidence , there is insufficient evidence to show any difference between the unilateral and bilateral approaches in both the PVP and PKP treatment in osteoporotic vertebral compression fractures . | OBJECTIVE The aim of this study was to compare the unilateral and bilateral approaches in treating osteoporotic vertebral compression fractures . | BACKGROUND Osteoporotic compression fractures ( OVCFs ) commonly occur in aged people , and as much as one-third of these fractures progress to chronic pain . Kyphoplasty ( KP ) is proved to be efficacious for pain relief and vertebral height restoration in chronic OVCFs , but there is still no data available about the clinical and radiographical outcomes compared by unipedicular and bipedicular KP in treating chronic painful OVCFs . PURPOSE To assess the clinical and radiographical outcomes in treating chronic painful OVCFs compared by unipedicular and bipedicular KP . METHODS Fifty-eight patients with a total of sixty-six chronic painful OVCFs were enroled in our study . They were r and omly allocated into two groups : group I ( n=33 ) was treated with unipedicular KP and group II ( n=25 ) with bipedicular KP . The operation times for each group were recorded and compared . Preoperative and postoperative of visual analogue scores ( VAS ) and oswestry disability index ( ODI ) scores were compared 2 weeks after surgery within each group and between groups . The radiographic outcomes were evaluated by the restoration rate ( RR ) in the most compressed point of the vertebral bodies . RESULTS Significant improvement on the VAS , ODI scores and RR was noted in each group ( p<0.001 ) , and there is no significant difference existing in clinical outcomes between the two groups . The mean operation time for each vertebra in group I was significantly shorter than in group II ( p<0.001 ) . But the RR in group II was higher than in group I ( p=0.041 ) . CONCLUSION Both unipedicular kyphoplasty and bipedicular kyphoplasty can achieve satisfactory clinical and radiographic outcomes in treating the chronic painful OVCFs and the operation time is shorter in unipedicular kyphoplasty . However , the bipedicular kyphoplasty is more efficacious in height restoration Background : Percutaneous vertebroplasty ( PVP ) has been demonstrated to be effective in the treatment of acute osteoporotic vertebral fracture ( AOVF ) . However , the matter of which surgical approach should be selected remains controversial . This research aims to compare the clinical results of unilateral and bilateral PVP for AOVF . Methods : From January 2008 to December 2011 , 68 patients with AOVF were r and omly assigned to the unilateral puncture group ( n=36 ) or the bilateral group ( n=32 ) . These patients underwent percutaneous injection of polymethyl methacrylate into posterior pedicle by the unilateral or bilateral puncture approach . Visual analogue scale ( VAS ) and the Quality of Life Question naire of the European Foundation for Osteoporosis ( QUALEFFO ) were recorded on presentation , at 1 week , 3 , 6 , and 12 months after operation . The cement leakage was measured by x-ray and computed tomography scan . Results : Follow-up data showed there were no significant differences in VAS and QUALEFFO between 2 groups at 1 week after PVP and only significant difference was observed between 2 groups at 3 , 6 , and 12 months after operation . The cement leakage was 52.7 % in the unilateral puncture group and 28.1 % in the bilateral group . Conclusions : Compared with unilateral puncture , use of bilateral approach during PVP may result in more superior long-term outcomes and less cement leakage for patients with AOVF To assess the immediate efficacy of percutaneous vertebroplasty ( PVP ) in relief of pain and improving mobility of patients with vertebral compression fractures ( VCF ) secondary to osteoporosis , 205 cases ( 175 patients ) underwent 250 percutaneous injections of polymethylmethacrylate ( PMMA ; unilateral , 247 levels ; bilateral , 3 levels ) into vertebrae under CT and fluoroscopic guidance for 34 months . Patients were prospect ively asked to quantify their pain on a visual analog scale ( VAS ) before and a day after PVP . The interval to mobilization was recorded in those who were immobilized because of pain and /or bed-rest therapy ( 115 cases ) . PVP was technically successful in all patients , with three cases of minimal complications . The mean VAS score available for 196 cases was improved from 7.22±1.89 ( range , 3–10 ) to 2.07±1.19 ( range , 0–10 ) by PVP . Ninety-four of 115 immobilized cases ( 81.7 % ) were mobile by 24 h after PVP , and the mean value was 1.9±2.8 days . The incidence of recurrent and new fractures was 15.6 % in 4–25 months ( mean , 15.3 months ) . PVP is a safe and effective treatment for relieving the pain associated with osteoporotic VCF and strengthening the vertebrae , avoiding refractures . This therapy leads to early mobilization and avoidance of the dangers of conservative therapy of bed-rest OBJECTIVE To evaluate the clinical efficacy of percutaneous bipediculary kyphoplasty with double or single balloon I treatment of osteoporosis vertebral compressive fractures . METHODS Fifty-one patients with painful osteoporotic vertebral compressive fracture involving 69 vertebrae . 19 males and 32 females , aged 72.5 ( 63 - 85 ) , underwent percutaneous kyphoplasty with double inflatable balloon ( 29 cases , 38 vertebrae ) or single inflatable balloon ( 22 cases , 31 vertebrae ) under X-ray fluoroscopy monitoring . The fractured vertebral bodies were punctuated , balloon was put into the subsided areas and then distended , and bone cement was injected into the cavity . The vertebral height and Cobb angle , preoperative and postoperative , were measured by radiography . Follow-up was conducted for 6 - 12 months . RESULTS All patients tolerated the procedure well with dramatic pain relief within 96 hours after the procedure . No clinical complication was found . Visual analog scale score was improved from 7.8 preoperatively to 2.6 postoperatively ( P < 0.01 ) . Oswestry disability index was decreased from 73 % preoperatively to 26 % postoperatively . In the double balloon group , the heights loss of the anterior and middle portions of the vertebral body reduced from 14.7 mm and 10.5 mm to 10.1 mm and 5.5 mm respectively ( both P < 0.01 ) , and the Cobb angle was corrected from 22.4 degrees to 12.3 degrees ( P < 0.01 ) . In the single balloon group , the heights loss of the anterior and middle portions of the vertebral body reduced from 14.7 mm and 10.6 mm to 10.4 mm and 6.5 mm respectively ( both P < 0.01 ) , and the . Cobb angle was corrected averagely from 21.2 degrees to 11.6 degrees ( P < 0.01 ) . The mean vertebral height restoration rates were 72.8 % and 70.1 % in the double and single balloon groups respectively . The mean Cobb angle correct degrees were 10.1 degrees and 9.5 degrees in double and single balloon groups respectively . There were no significant differences in the average height restoration rate and Cobb angle correction between the double and single balloon groups ( 72.8 % vs 70.1 % , and 10.0 degrees vs 9.5 degrees both P > 0.05 ) . The pain relief and functional recovery were substantial and maintained to the last follow up . CONCLUSION Percutaneous bipediculary kyphoplasty with double or single balloon for painful osteoporotic vertebral body compressive fractures is effective and safe The Scottish Intercollegiate Guidelines Network ( SIGN ) develops evidence based clinical guidelines for the NHS in Scotl and . The key elements of the methodology are ( a ) that guidelines are developed by multidisciplinary groups ; ( b ) they are based on a systematic review of the scientific evidence ; and ( c ) recommendations are explicitly linked to the supporting evidence and grade d according to the strength of that evidence . Until recently , the system for grading guideline recommendations was based on the work of the US Agency for Healthcare Research and Quality ( formerly the Agency for Health Care Policy and Research ) . 1 2 However , experience over more than five years of guideline development led to a growing awareness of this system 's weaknesses . Firstly , the grading system was design ed largely for application to questions of effectiveness , where r and omised controlled trials are accepted as the most robust study design with the least risk of bias in the results . However , in many areas of medical practice r and omised trials may not be practical or ethical to undertake ; and for many questions other types of study design may provide the best evidence . Secondly , guideline development groups often fail to take adequate account of the method ological quality of individual studies and the overall picture presented by a body of evidence rather than individual studies or they fail to apply sufficient judgment to the overall strength of the evidence base and its applicability to the target population of the guideline . Thirdly , guideline users are often not clear about the implication s of the grading system . They misinterpret the grade of recommendation as relating to its importance , rather than to the strength of the supporting evidence , and may therefore fail to give due weight to low grade recommendations . # # # # Summary points A revised system of determining levels of evidence and grade s Purpose To investigate the effect of treatment of multiple myeloma (MM)-associated spinal fracture with percutaneous vertebroplasty ( PVP ) and chemotherapy . Methods Patients with MM-associated spinal fracture were r and omly divided into combined ( PVP and chemotherapy ) treatment group ( n = 38 ) and single chemotherapy group ( n = 38 ) . For the combined treatment group , bone cement was injected into vertebral body via DSA guided-percutaneous puncture . M2 scheme was used for both groups . And a 5-year follow-up was conducted for the study . Results At the 1-year follow-up visits , PVP combined with chemotherapy achieved complete remission ( CR ) in six patients ( 15.8 % ) ; near complete remission ( nCR ) in ten patients ( 26.30 % ) ; partial remission ( PR ) in nine patients ( 23.7 % ) ; minimal response ( MR ) in three patients ( 7.9 % ) ; no change ( NC ) in four patients ( 10.5 % ) , and disease progression ( DP ) in five patients ( 13.2 % ) . Only chemotherapy alone result ed in 3 CR ( 7.9 % ) ; 8 nCR ( 26.30 % ) ; 19 PR ( 77.5 % ) ; 4 MR ( 17.5 % ) ; 4 NC ( 17.5 % ) , and 2 DP ( 5.0 % ) . While the overall response rate ( ORR ) in the combined treatment group ( 65.8 % ) and the single chemotherapy group ( 50.0 % ) were significantly different , their visual analog pain scales ( 3.01 ± 0.62 and 5.97 ± 0.40 , respectively ) and Karnofsky performance scores ( 89.4 ± 6.3 and 80.3 ± 7.2 , respectively ) were significantly improved after treatment ( P = 0.032 and P = 0.002 , respectively ) . And the ORR between the two groups were significantly different ( P = 0.001 ) . Conclusion Percutaneous vertebroplasty is a minimally invasive surgery for MM-associated pathologic fracture . PVP had the characteristics of minimal trauma , easy operation and less complication . PVP can achieve long-term analgesic effect , and enhance the spinal stability Study Design . A prospect i ve study of patients who underwent multilevel balloon kyphoplasty at a single institute . Objective . To examine and compare the safety and long-term radiographic and clinical effects of unilateral or bilateral balloon kyphoplasty to treat multilevel symptomatic vertebral compression fractures . Summary of Background Data . Typically , balloon kyphoplasty involves placement of inflatable bone tamp via a bilateral transpedicular or extrapedicular approach . Recently , several articles reported unilateral kyphoplasty with comparable outcomes . However , few prospect i ve r and omized study comparing the radiographic and clinical outcomes using unilateral and bilateral approaches was reported . Methods . Forty-nine patients with 114 Osteoporotic vertebral compression fractures were r and omly allocated into two groups adopting unilateral or bilateral balloon kyphoplasty . Preoperative and postoperative pain scores , back disability , and 36-Item Short Form Health Survey scores were compared with at least a 2-year follow-up . Vertebral body height and vertebral body kyphotic angle from this cohort were analyzed before surgery , after surgery , and at final follow-up . Results . Both unilateral and bilateral balloon kyphoplasty result ed in significant pain reduction and back dysfunction improvement and remained unchanged at final follow-up . Quality of life assessment using 36-Item Short Form Health Survey recorded marked and significant improvements in all mean subscale scores except general health and social function . Regarding the pain reduction , back dysfunction , and 36-Item Short Form Health Survey scores , no significant difference existed between two groups . Significant increases of anterior and middle vertebral heights were recorded for both groups after surgery and maintained for the period of follow-up . The mean correction of vertebral body kyphotic angle was about 7 ° in both groups . Asymptomatic cement extravasation occurred in six of 49 of patients , and three patients developed additional fractures at untreated levels during the period of follow-up . Conclusions . Both unilateral and bilateral kyphoplasty markedly improve symptom-related clinical effects of multilevel vertebral compression fractures and result in significant vertebral height restoration and kyphosis correction that remains stable for at least 2 years after treatment |
13,562 | 27,913,990 | Overall , sirukumab has been reported to be a safe and well-tolerated agent , capable of modulating the immune response in healthy population s as well as in subjects with inflammatory disorders ( e.g. , rheumatoid arthritis ) .
Amongst individuals with complex brain-based disorders ( e.g. , mood disorders ) , the dimensions/domains most likely to benefit with sirukumab are negative valence disturbances ( e.g. , anxiety , depression , rumination ) , positive valence disturbances ( e.g. , anhedonia ) as well as general cognitive processes .
We suggest that sirukumab represents a prototype and possibly a proof-of-concept that agents that engage IL-6 targets have salutary effects in psychiatry | Convergent evidence indicates that abnormalities in the innate immune system may be pertinent to the pathogenesis , phenomenology , and possible treatment of several mental disorders .
In keeping with this view , the targeting of interleukin-6 with the human monoclonal antibody sirukumab may represent a possible treatment and disease modification approach , for adults with brain-based disorders ( e.g. , major depressive disorder ) . | Objectives The safety and efficacy of sirukumab , an anti-interleukin-6 ( IL-6 ) monoclonal antibody , were evaluated in a 2-part , placebo-controlled phase II study of patients with active rheumatoid arthritis ( RA ) despite methotrexate therapy . Methods In Part A ( proof-of-concept ) , 36 patients were r and omised to placebo or sirukumab 100 mg every 2 weeks ( q2w ) through week 10 , with crossover treatment during weeks 12–22 . In Part B ( dose finding ) , 151 patients were r and omised to sirukumab ( 100 mg q2w , 100 mg q4w , 50 mg q4w , or 25 mg q4w ) through week 24 , or placebo through week 10 with crossover to sirukumab 100 mg q2w ( weeks 12–24 ) . The proportion of patients with an American College of Rheumatology 50 ( ACR50 ) response and the change from baseline in the 28-joint count disease activity score using C-reactive protein ( DAS28-CRP ) were determined . Safety was evaluated through week 38 in both parts . Results The primary endpoint ( ACR50 at week 12 in Part B ) was achieved only with sirukumab 100 mg q2w versus placebo ( 26.7 % vs 3.3 % ; p=0.026 ) . Greater improvements in mean DAS28-CRP at week 12 were observed with sirukumab 100 mg q2w versus placebo in Parts A ( 2.1 vs 0.6 , p<0.001 ) and B ( 2.2 vs 1.1 ; p<0.001 ) . The incidence of adverse events ( AEs ) was similar for sirukumab-treated and placebo-treated patients through week 12 in Part A ( 70.6 % and 63.2 % , respectively ) and B ( 67.8 % and 66.7 % , respectively ) . Infections were the most common type of AE ; one death occurred ( Part B , sirukumab 100 mg q2w , brain aneurysm ) . Conclusions Sirukumab-treated patients experienced improvements in the signs/symptoms of RA . Safety results through 38 weeks were consistent with other IL-6 inhibitors . Trial registration number NCT00718718 CONTEXT Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse , and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants . OBJECTIVES To determine whether inhibition of the inflammatory cytokine tumor necrosis factor ( TNF ) reduces depressive symptoms in patients with treatment-resistant depression and whether an increase in baseline plasma inflammatory biomarkers , including high-sensitivity C-reactive protein ( hs-CRP ) , TNF , and its soluble receptors , predicts treatment response . DESIGN Double-blind , placebo-controlled , r and omized clinical trial . SETTING Outpatient infusion center at Emory University in Atlanta , Georgia . PARTICIPANTS A total of 60 medically stable out patients with major depression who were either on a consistent antidepressant regimen ( n = 37 ) or medication-free ( n = 23 ) for 4 weeks or more and who were moderately resistant to treatment as determined by the Massachusetts General Hospital Staging method . INTERVENTIONS Three infusions of the TNF antagonist infliximab ( 5 mg/kg ) ( n = 30 ) or placebo ( n = 30 ) at baseline and weeks 2 and 6 of a 12-week trial . MAIN OUTCOME MEASURES The 17-item Hamilton Scale for Depression ( HAM-D ) scores . RESULTS No overall difference in change of HAM-D scores between treatment groups across time was found . However , there was a significant interaction between treatment , time , and log baseline hs-CRP concentration ( P = .01 ) , with change in HAM-D scores ( baseline to week 12 ) favoring infliximab-treated patients at a baseline hs-CRP concentration greater than 5 mg/L and favoring placebo-treated patients at a baseline hs-CRP concentration of 5 mg/L or less . Exploratory analyses focusing on patients with a baseline hs-CRP concentration greater than 5 mg/L revealed a treatment response ( ≥50 % reduction in HAM-D score at any point during treatment ) of 62 % ( 8 of 13 patients ) in infliximab-treated patients vs 33 % ( 3 of 9 patients ) in placebo-treated patients ( P = .19 ) . Baseline concentrations of TNF and its soluble receptors were significantly higher in infliximab-treated responders vs nonresponders ( P < .05 ) , and infliximab-treated responders exhibited significantly greater decreases in hs-CRP from baseline to week 12 compared with placebo-treated responders ( P < .01 ) . Dropouts and adverse events were limited and did not differ between groups . CONCLUSIONS This proof-of-concept study suggests that TNF antagonism does not have generalized efficacy in treatment-resistant depression but may improve depressive symptoms in patients with high baseline inflammatory biomarkers . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00463580 Rationale Premature discontinuation of antidepressant drugs is a frequent clinical problem . Adverse effects are common , occur early on in treatment and are reported to be one of the main reasons for discontinuation of antidepressant treatment . Objectives To investigate the association between adverse effects occurring in the first 2 weeks of antidepressant treatment and discontinuation by 6 weeks as the outcome . To investigate the time profile of adverse effects induced by the selective serotonin reuptake inhibitor citalopram and the noradrenaline reuptake inhibitor reboxetine over 12 weeks of treatment . Methods Six hundred and one depressed individuals were r and omly allocated to either citalopram ( 20 mg daily ) or reboxetine ( 4 mg twice daily ) . A modified version of the Toronto Side Effects Scale was used to measure 14 physical symptoms at baseline ( medication free ) and at 2 , 6 and 12 weeks after r and omisation . Results Individuals r and omised to reboxetine reported a greater number of adverse effects and were more likely to stop treatment than individuals receiving citalopram . Dizziness ( OR 1.83 ; 95 % CI 1.09 , 3.09 ; p = 0.02 ) and the total number of adverse effects ( OR 1.12 ; 95 % CI 1.00 , 1.25 ; p = 0.06 ) reported at 2 weeks were associated with discontinuation from overall antidepressant treatment by 6 weeks . Reports of adverse effects tended to reduce throughout the 12 weeks for both antidepressants . Conclusions The majority of adverse effects were not individually associated with discontinuation from antidepressant treatment . Reports of physical symptoms tended to reduce over time . The physical symptoms that did not reduce over time may represent symptoms of depression rather than antidepressant-induced adverse effects OBJECTIVE Major depressive disorder has been linked with inflammatory processes , but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial . The authors tested the hypothesis that C-reactive protein ( CRP ) , a commonly available marker of systemic inflammation , predicts differential response to escitalopram ( a serotonin reuptake inhibitor ) and nortriptyline ( a norepinephrine reuptake inhibitor ) . METHOD The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression ( GENDEP ) study , a multicenter open-label r and omized clinical trial . CRP was measured with a high-sensitivity method in serum sample s from 241 adult men and women with major depressive disorder r and omly allocated to 12-week treatment with escitalopram ( N=115 ) or nortriptyline ( N=126 ) . The primary outcome measure was the score on the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , administered weekly . RESULTS CRP level at baseline differentially predicted treatment outcome with the two antidepressants ( CRP-drug interaction : β=3.27 , 95 % CI=1.65 , 4.89 ) . For patients with low levels of CRP ( < 1 mg/L ) , improvement on the MADRS score was 3 points higher with escitalopram than with nortriptyline . For patients with higher CRP levels , improvement on the MADRS score was 3 points higher with nortriptyline than with escitalopram . CRP and its interaction with medication explained more than 10 % of individual-level variance in treatment outcome . CONCLUSIONS An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice OBJECTIVE Sirukumab ( CNTO 136 ) is a human mAb with high affinity and specificity for binding to interleukin-6 . This Phase 1 study evaluated the pharmacokinetics , immunogenicity , safety , and tolerability of sirukumab following a single subcutaneous ( s.c . ) administration in healthy male Japanese and Caucasian subjects . METHODS Japanese and Caucasian subjects were r and omized to placebo or 25 , 50 , or 100 mg sirukumab . Blood sample s were collected to measure serum sirukumab concentration and antibodies to sirukumab . Noncompartmental analysis and population pharmacokinetic modeling were conducted to characterize sirukumab pharmacokinetics . Adverse events were monitored at each visit . RESULTS 25 Japanese and 24 Caucasian subjects received sirukumab and were included in the pharmacokinetic evaluation . Mean Cmax and AUC0-∞of sirukumab increased in an approximately dose-proportional manner in both Japanese and Caucasian subjects . Median tmax was 3 -5 days after s.c . administration of sirukumab . Mean t1/2 was 15 -16 days in Japanese and 15 -18 days in Caucasian subjects . A one-compartment population pharmacokinetic model adequately described sirukumab pharmacokinetics following s.c . administration . The estimated population means for CL/F , V/F , and Ka were 0.54 ±0.03 l/day , 12.2 ±0.55 l , and 0.77 ±0.07 day-1 , respectively . Race was not a significant covariate on CL/F or V/F. No subject was positive for antibodies to sirukumab . Adverse events were generally mild and did not appear to be dose-related or lead to study discontinuation . CONCLUSIONS Sirukumab pharmacokinetics following subcutaneous administration was linear at doses ranging 25 -100 mg and was comparable between Japanese and Caucasian subjects . A single subcutaneous administration of 25 , 50 , or 100 mg sirukumab appeared to be well tolerated by both Japanese and Caucasian healthy male subjects In a controlled study , such immunological parameters as whole blood production of the cytokines interleukin-6 ( IL-6 ) and tumor-necrosis factor-α ( TNF-α ) were assessed in 24 in patients with a major depressive disorder ( MDD ) both before and again under treatment . After a 6-week treatment period with amitriptyline , patients were classified as responders or nonresponders according to their psychopathological outcome as evaluated by the Hamilton and the Montgomery – Asberg Depression Rating Scales . Pre-treatment levels of c-reactive protein ( CRP ) were significantly higher in both patient subgroups than in the control subjects . In comparison to the controls , unstimulated pretreatment production of IL-6 was significantly decreased in the responders ; whereas it was significantly increased in the nonresponder subgroup . Post-treatment values did not differ significantly among the patient and control groups . Pretreatment levels of TNF-α were increased in both patient subgroups , with a significant decrease during treatment only in the responder subgroup . Pretreatment levels of IL-6/105 mononuclear cells and the ratio between lymphocytes and monocytes acted as independent variables with regard to the clinical response . Our data indicate that unstimulated secretion of TNF-α is related to the psychopathological improvement ; whereas , IL-6 levels might dichotomize the patients into subsequent responders and nonresponders already at admission OBJECTIVE We undertook a 2-part , phase I , double-blind , placebo-controlled study to evaluate the safety and pharmacokinetics of multiple intravenous infusions of sirukumab , a human anti-interleukin-6 monoclonal antibody , in patients with cutaneous lupus erythematosus ( CLE ) or systemic lupus erythematosus ( SLE ) . METHODS In part A , patients with histologically confirmed CLE were r and omized to 4 infusions of placebo or 1 , 4 , or 10 mg/kg sirukumab every 2 weeks . In part B , SLE patients diagnosed according to American College of Rheumatology criteria with a score of 5 - 12 on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index were r and omized to 4 infusions of placebo or 10 mg/kg sirukumab every 2 weeks . RESULTS We treated 31 CLE patients ( 23 with sirukumab , 8 with placebo ) and 15 SLE patients ( 10 with sirukumab , 5 with placebo ) . Adverse events ( AEs ) occurred more often with sirukumab than placebo in CLE patients ( 91 % versus 63 % ) and in SLE patients ( 90 % versus 80 % ) . Sirukumab led to sustained , dose-independent decreases in white blood cell counts , absolute neutrophil counts ( neutropenia ) , and platelet counts ( thrombocytopenia ) and to minor elevations in total cholesterol levels . The majority of infections were mild respiratory infections . which were reported similarly across CLE cohorts but more often in sirukumab-treated than in placebo-treated SLE patients . Two serious AEs of infection occurred ( pneumonia in the 10 mg/kg-treated group and iatrogenic wound infection in the 4 mg/kg-treated group ) . Sirukumab showed linear pharmacokinetics in CLE patients . Systemic exposure and half-life were comparable between CLE and SLE patients . No patient developed antibodies to sirukumab through 22 weeks . C-reactive protein and serum amyloid A mean concentrations were suppressed with sirukumab from week 1 to week 14 . CONCLUSION Treatment with intravenous sirukumab infusions was generally well tolerated in both CLE and SLE patients with mild , stable , active disease . Sirukumab demonstrated linear pharmacokinetics over the dose range studied and comparable systemic exposure and half-life in CLE and SLE patients |
13,563 | 25,733,466 | Results differed little when the analyses were restricted to studies with a low risk of bias and duration of ≥7 d. CONCLUSIONS This meta- analysis revealed no evidence that , in trials with a short intervention and large reductions in sodium , circulating glucose concentrations differed between groups . | BACKGROUND Although evidence shows that reduced sodium intake lowers blood pressure , some studies suggest that sodium reduction may adversely affect insulin resistance and glucose tolerance .
OBJECTIVES The objectives were to assess the effects of sodium reduction on glucose tolerance , evaluate strengths and weaknesses of the relevant scientific literature , and provide direction for future research . | Low-salt ( LS ) diet activates the renin-angiotensin-aldosterone and sympathetic nervous systems , both of which can increase insulin resistance ( IR ) . We investigated the hypothesis that LS diet is associated with an increase in IR in healthy subjects . Healthy individuals were studied after 7 days of LS diet ( urine sodium < 20 mmol/d ) and 7 days of high-salt ( HS ) diet ( urine sodium > 150 mmol/d ) in a r and om order . Insulin resistance was measured after each diet and compared statistically , unadjusted and adjusted for important covariates . One hundred fifty-two healthy men and women , aged 39.1 ± 12.5 years ( range , 18 - 65 ) and with body mass index of 25.3 ± 4.0 kg/m(2 ) , were included in this study . Mean ( SD ) homeostasis model assessment index was significantly higher on LS compared with HS diet ( 2.8 ± 1.6 vs 2.4 ± 1.7 , P < .01 ) . Serum aldosterone ( 21.0 ± 14.3 vs 3.4 ± 1.5 ng/dL , P < .001 ) , 24-hour urine aldosterone ( 63.0 ± 34.0 vs 9.5 ± 6.5 μg/d , P < .001 ) , and 24-hour urine norepinephrine excretion ( 78.0 ± 36.7 vs 67.9 ± 39.8 μg/d , P < .05 ) were higher on LS diet compared with HS diet . Low-salt diet was significantly associated with higher homeostasis model assessment index independent of age , sex , blood pressure , body mass index , serum sodium and potassium , serum angiotensin II , plasma renin activity , serum and urine aldosterone , and urine epinephrine and norepinephrine . Low-salt diet is associated with an increase in IR . The impact of our findings on the pathogenesis of diabetes and cardiovascular disease needs further investigation Our recent studies have indicated that severe salt restriction aggravates vascular insulin resistance in younger normotensive and hypertensive subjects . However , whether the extent of dietary salt restriction commonly advocated adversely affects vascular insulin resistance is unknown . To determine whether moderate dietary salt restriction might affect vascular and systemic sensitivity to insulin , we studied eight subjects after 1 week of a normal sodium diet ( 235 mEq/day ) and 1 week of a moderate salt restriction ( 75 meq/day ) . Systemic insulin resistance as assessed by the fasting plasma glucose-to-insulin ratio was aggravated by dietary sodium restriction ( normal sodium : 1.2 + /- 0.1 mmol/mIU ; low sodium 0.6 + /- 0.1 , P < .05 ) . Salt restriction significantly reduced maximal insulin-mediated vasodilation ( normal sodium : 51 % + /- 5 % of maximum nitroglycerin-mediated response ; low sodium : 28 % + /- 6 % , P < .01 ) . In contrast , no alterations in nitroglycerin-mediated vasodilation nor phenylephrine-mediated vasoconstriction were noted . These studies demonstrate that moderate salt restriction aggravates both systemic and vascular insulin resistance . This impairment of the vasodilating effect of insulin could be a factor attenuating the blood pressure lowering effect of a low sodium diet To assess the effects of sodium reduction on insulin sensitivity in hypertension , we examined the change of insulin sensitivity after two degrees of dietary sodium restriction by the euglycemic hyperinsulinemic glucose clamp method in 12 subjects with primary hypertension . A controlled period of 1 week , when the subjects were taking a normal sodium diet , was followed by a r and omized crossover study in which the subjects were placed on either moderate or strict reduced sodium diets for 1 week . The result of the 1-week moderate dietary sodium reduction from 200 to 100 mmol/day showed significant decreases in systolic and diastolic blood pressure by 6.5 and 5.0 mm Hg , respectively . Strict dietary sodium reduction to 30 mmol/day for 1 week result ed in no further decrease in blood pressure , but it increased plasma insulin by 40.6 % without changing plasma glucose . There were no changes in glucose infusion rate ( GIR ) or insulin sensitivity index ( ISI ) , which is a measure of GIR divided by plasma insulin , after moderate dietary sodium reduction . However , strict dietary sodium reduction induced decreases in GIR by 19.8 % ( from 1318+/-189 to 1057+/-173 micromol/m2/ min ; P < .01 ) , and ISI by 20.5 % ( from 16.6+/-2.1 to 13.2+/-1.9 micromol/m2/min/microU/mL ; P < .01 ) with a paralleled increase of plasma norepinephrine by 90.0 % ( from 150.5+/-61.6 to 287.3+/-114.9 pg/mL ; P < .01 ) . These results indicate that dietary sodium restriction leads to a deterioration of insulin sensitivity when plasma norepinephrine levels increase , and suggest that moderate dietary sodium reduction may lower blood pressure without a distinct adverse effect on glucose metabolism in subjects with primary hypertension OBJECTIVES To investigate the relationship between salt sensitivity and hyperinsulinaemia in rural black African subjects . DESIGN An intervention study where 27 subjects were divided into two groups ; group 1 was initially salt loaded ( 300 mmol Na+/day ) , while group 2 was salt restricted ( 25 mmol Na+/day ) , each for 4 days , after which a cross-over study was done . SETTING Chidamoyo , a rural area 383 km north of Harare , Zimbabwe . SUBJECTS Twenty-seven rural volunteers ( 16 women , 11 men ) . OUTCOME MEASURES Systolic and diastolic blood pressures , salt sensitivity , insulin and glucose levels , body mass index and mean arterial pressure . RESULTS Mean arterial pressure , which was 91 + /- 2 mmHg on a low-salt diet , increased significantly ( P < 0.01 ) to 105 + /- 3 mmHg on high-salt diet in the salt-sensitive subjects . In the same salt-sensitive subjects , the fasting insulin level was 8.4 + /- 0.8 microU/ml on a low-salt and 6.1 + /- 1.0 microU/ml on a high-salt diet . The difference was not statistically significant . CONCLUSIONS Although salt pressor sensitivity was demonstrated in the subjects , there was no accompanying increase but rather a decrease in fasting insulin levels , suggesting that in the short term , salt sensitivity and hyperinsulinaemia are not linked in raising blood pressure in this sample of rural Zimbabwean subjects Dietary salt restriction lowers blood pressure and has been advocated as a population -based strategy to reduce the cardiovascular morbidity associated with hypertension . However , the effect of lowering salt intake on metabolic vascular risk factors such as insulin resistance and levels of atherogenic lipids and fasting insulin is uncertain . We have studied the short-term effect of moderate dietary salt restriction on insulin resistance and serum lipids in 34 nonobese ( body mass index [ mean + /- SD ] 23.4 + /- 1.8 kg/m2 ) , normotensive young white men . Subjects were maintained on a low salt diet ( < 80 mmol/day ) for the 2-week study period . In a r and omized , cross-over , double-blind fashion , each subject also received 120 mmol of sodium chloride per day during one of the study weeks , and a matching placebo during the other . Insulin resistance , serum insulin , lipids , and blood pressure were measured in the fasting state at the end of each study week . Urinary sodium excretion ( 185 + /- 46 v 52 + /- 25 mmol/day , P < .001 ) , serum sodium ( 141.2 + /- 1.2 v 140.1 + /- 1.3 mmol/L , P < .001 ) and body weight ( 75.4 + /- 9.1 v 75.0 + /- 9.3 kg , P < .05 ) were higher during the high salt than the low salt period . Serum creatinine was higher during the low salt period ( 100 + /- 8 v 90 + /- 9 mumols/L , P < .01 ) . There was no difference in blood pressure , insulin resistance , serum insulin , C-peptide , total cholesterol , low density lipoprotein cholesterol , high density lipoprotein cholesterol or its subfractions , triglycerides , apolipoprotein A1 , or apolipoprotein B between the high salt and low salt periods . We conclude that short-term , moderate dietary salt restriction does not adversely affect insulin sensitivity or levels of atherogenic lipids in normotensive nonobese men A case-control design involving only cases may be used when brief exposure causes a transient change in risk of a rare acute-onset disease . The design resembles a retrospective nonr and omized crossover study but differs in having only a sample of the base population -time . The average incidence rate ratio for a hypothesized effect period following the exposure is estimable using the Mantel-Haenszel estimator . The duration of the effect period is assumed to be that which maximizes the rate ratio estimate . Self-matching of cases eliminates the threat of control- selection bias and increases efficiency . Pilot data from a study of myocardial infa rct ion onset illustrate the control of within-individual confounding due to temporal association of exposures Insulin resistance was demonstrated in hypertensive patients and in salt-sensitive subjects . It was recently reported that the salt-sensitive state was related to a reduced fall in blood pressure during the night in essential hypertension . In the present study , the relationship among insulin sensitivity , blood pressure response to salt intake , and nocturnal fall in blood pressure was examined in 20 subjects with nondiabetic and nonobese essential hypertension during a low-salt and a high-salt diet . The subjects were maintained on a low-salt diet ( 50 mmol/d ) and a high-salt diet ( 255 mmol/d ) for 1 week each , in r and om order . On the sixth day of each diet , blood pressure was measured every hour for 24 hours with an automatic device . Insulin sensitivity was measured according to the steady-state plasma glucose ( SSPG ) method on the seventh day of each diet . Salt-induced increase in blood pressure , which we defined as the change in 24-hour mean arterial pressure between the low and the high dietary salt intakes , was significantly correlated with SSPG ( r=0.60 , P<0.01 ) during the high-salt period . There was a significant negative correlation ( r=-0.61 , P<0.01 ) between SSPG and a nocturnal fall in mean arterial pressure during the high-salt period . Salt-induced increase in blood pressure was inversely correlated with a nocturnal fall in mean arterial pressure ( r=-0.52 , P<0.02 ) with the high-salt diet . These results suggest that insulin resistance , salt sensitivity , and failed nocturnal fall in blood pressure are associated with each other in subjects with essential hypertension Evidence suggests that dietary salt reduction similar to diuretic therapy may adversely affect lipid and glucose metabolism . We studied 147 non-obese normotensive subjects ( 60 females and 87 males ) aged 19 - 78 years who entered a single-blind crossover trial and were r and omly assigned to a low salt diet of 20 mmol or a high salt diet of 300 mmol sodium per day , for 7 days each . Sodium restriction lowered mean arterial blood pressure ( MAP ) by a mean of 7.5 mmHg in 17 % ( salt-sensitive ) , had no hemodynamic effect in 67 % ( salt-resistant ) and raised MAP by a mean of 6 mmHg in 16 % of the subjects ( reverse reactors ) . With dietary salt restriction serum total- and LDL-cholesterol as well as serum insulin and uric acid concentrations increased significantly in all three groups . The largest increases in total ( 10 % ) and LDL- ( 12 % ) cholesterol occurred in the reverse reactors . Salt-sensitives had significant higher lipoprotein(a ) values than the other two groups . Salt-restriction had no significant effect on this parameter . Plasma renin activity , as well as plasma aldosterone and noradrenaline concentrations rose in all three groups during the low salt diet , the largest increases being observed in the reverse reactors . Short-term sodium restriction in normotensive adults has unfavourable effects on lipid and glucose metabolism , especially in subjects who do not derive hemodynamic benefit . Further studies are necessary to examine the effects of more moderate salt reduction for longer periods on the risk factor profile for cardiovascular disease before a low salt diet can be regarded as a safe public health measure for the general population We have previously reported that modest dietary sodium restriction , as advocated in management guidelines for diabetes , may reduce insulin sensitivity . It has since been suggested that this effect may be mediated via cross-talk between insulin and angiotensin II (AII)-stimulated intracellular second messengers . In order to assess the effect of 5 days of modest sodium restriction ( to < 80 mmol/day target sodium intake ) on insulin sensitivity , 15 healthy males underwent a double-blind , placebo-controlled , r and omized , cross-over euglycaemic hyperinsulinaemic clamp study . One phase was supplemented with sodium tablets and the other with matched placebo . Insulin sensitivity ( M ) was reduced during dietary sodium restriction [ median M value , 10.2 mg/kg per min ( interquartile range 9.50 - 13.85 ) versus 12.8 mg/kg per min ( interquartile range 9.60 - 14.30 ) , P < 0.05 ] . To eluci date potential mechanisms that may explain this observation , we investigated the effect of AII on insulin action in isolated adipocytes obtained from healthy females . No effect of AII on insulin-mediated glucose transport or suppression of lipolysis was observed . In conclusion , despite the observation that dietary sodium restriction was associated with a median 15 % reduction in insulin sensitivity , we found no evidence of a direct effect of AII on insulin action in human adipocytes Severe short-term sodium restriction or extreme sodium loading may alter glucose tolerance and insulin resistance in patients with hypertension , but it is unclear whether variations in sodium intake within the clinical ly observed range affect glucose tolerance . To examine this issue , 21 patients with primary hypertension with average sodium excretion of 116+/-55 mEq/day were r and omized to consecutive 4-week periods of placebo therapy and sodium chloride supplementation 2 g four times a day in a single-blind crossover study design . A 75-g oral glucose tolerance test ( GTT ) with simultaneous insulin levels was performed at the end of each intervention period . For the group as a whole , urinary sodium excretion increased on sodium chloride to 267+/-118 mEq/day versus control ( placebo ) phase of 135+/-53 mEq/day , P < .001 . Total glycemic response in the oral GTT ( area under the glucose curve ) was 8.0 % lower during sodium supplementation , P < .001 . Secondary analysis revealed that the effect of sodium was noteworthy in 1 ) type 2 diabetic subjects ( n = 8) , 2 ) sodium-sensitive subjects ( n = 10 ) , and 3 ) nondiabetic subjects receiving antihypertensive drug treatment ( n = 6 ) . The total insulinemic response to oral GTT was also lowered by sodium loading among diabetic subjects . Thus , an abundant sodium intake may improve glucose tolerance and insulin resistance , especially in diabetic , salt-sensitive , and or medicated essential hypertensive subjects Hypertension in obese patients is associated with hyperinsulinemia and salt sensitivity . Very low salt diets may exacerbate hyperinsulinemia , perhaps by activating the renin-angiotensin system . Therefore , the effects of a low salt diet alone and with enalapril on blood pressure and the insulin response to an oral glucose tolerance test were studied in 9 obese ( body mass index 35 + /- 2 kg/m2 ) men with mild hypertension . Measurements were first obtained after a 2-week high-salt ( 20 mEq/day sodium diet+eleven 1 g salt tablets per day ) baseline period . The same measurements were repeated after 2 weeks on a low salt diet ( 20 mEq/day ) and after 2 weeks on low salt diet with enalapril in r and om sequence . The insulin area under the curve increased from 12.8 + /- 3.0 mU-min/dl during high salt to 16.6 + /- 3.2 mU-min/dl ( p < 0.001 ) . Plasma renin activity also increased with salt restriction from 1.4 + /- 0.2 to 3.0 + /- 0.5 ng/ml/hour , p = 0.01 . With addition of enalapril to the low sodium chloride diet , the insulin area under the curve ( 14.5 + /- 2.6 mU-min/dl ) was not significantly different from that during the high sodium chloride phase . Mean blood pressure in the laboratory was 105 + /- 1 mm Hg with high salt versus 99 + /- 1 mm Hg with low salt , p < 0.05 . Addition of enalapril to the low-salt diet reduced mean blood pressure to 87 + /- 1 mm Hg ( p < 0.01 vs low salt ) , largely by reducing total systemic resistance ( p < 0.05 ) . Salt restriction decreases laboratory BP while raising insulin levels in obese men with mild hypertension . ( ABSTRACT TRUNCATED AT 250 WORDS Acute reduction of salt intake causes an increase in serum lipid and insulin levels in healthy volunteers and patients with essential hypertension , suggesting induction of insulin resistance by salt restriction . Direct measurements of insulin sensitivity using the euglycaemic clamp showed no significant change after 7 days of salt restriction . Our previous study showed a time dependent course of dyslipidaemia after institution of a low salt diet . We therefore assessed insulin sensitivity ( M-value ) under euglycaemic conditions ( clamp technique ) at discrete time points using a parallel group design . Two groups of healthy males were examined on high ( 200 mmol d-1 ) and low ( 20 mmol d-1 ) salt intake . One group ( n = 7 , 25 + /- 3 years , BMI 22.4 + /- 2.1 kg m-2 ) received high and low salt diet in r and om order each for 7 days . The other group ( n = 7 , 26 + /- 3 years , 22.1 + /- 1.9 kg m-2 ) received the respective diet in r and om order for 3 days . A significantly ( P < 0.01 ) different mean M-value was noted in the group receiving the diets for 3 days , i.e. after low salt intake it was 7.4 + /- 1.2 mg kg-1 min-1 and after high salt intake 8.6 + /- 1.1 mg kg-1 min-1 . In contrast , the mean M-value was similar after low and high salt periods in the group of individuals who had been studied after 7 days on either salt take ( 7.8 + /- 1.8 on low salt vs. 7.6 + /- 1.3 mg kg-1 min-1 on high salt ) . ( ABSTRACT TRUNCATED AT 250 WORDS Dietary sodium restriction has a variety of effects on metabolism , including activation of the renin-angiotensin system . Angiotensin II has complex metabolic and cardiovascular effects , and these may be relevant to the effects of both nonpharmacological and pharmacological interventions in noninsulin-dependent diabetes mellitus ( NIDDM ) . We have assessed the effect of dietary sodium restriction on insulin sensitivity and endogenous glucose production in eight normotensive patients with diet-controlled NIDDM who underwent hyperinsulinemic clamp studies in a r and omized , double-blind , placebo-controlled cross-over protocol after two 4-day periods on sodium replete ( 160 mmol/day ) and sodium deplete ( 40 mmol/day ) diets . Mean + /- SD 24-h urinary sodium was 197 + /- 76.0 mmol ( replete ) and 67 + /- 19.5 mmol ( deplete ) , P = 0.03 . Insulin sensitivity was 42.0 + /- 11.3 mumol/kg.min ( replete ) and 37.0 + /- 11.6 mumol/kg.min ( deplete ) , P = 0.04 ( a reduction of 12 % ) . Blood pressure was 130 + /- 21/78 + /- 11 mmHg ( replete ) and 128 + /- 12/73 + /- 10 mmHg ( deplete ) . Dietary sodium restriction may result in a decrease in peripheral insulin sensitivity in normotensive patients with NIDDM , possibly via an elevation in prevailing angiotensin II concentrations Recent studies have shown that insulin has a direct vasodilator effect and that vascular sensitivity to insulin is impaired in hypertension . How the vasodilator effect of insulin is regulated physiologically is unknown . It has been appreciated that salt restriction may have adverse effects on glucose and lipid metabolism — processes regulated by insulin . To determine whether dietary salt restriction might affect vascular sensitivity to insulin , we studied 13 subjects ( including eight borderline hypertensive subjects and five normotensive subjects ) after 1 week of a normal sodium diet ( 240 mEq/day ) and after 1 week of a low‐sodium diet ( 20 mEq/day ) with a r and omized , double‐blind crossover design The aims of the present study were to investigate the effects of changes in sodium intake in patients with untreated mild essential hypertension on the hormonal ( plasma renin activity and aldosterone ) and renal tubular responses to short-term hyperinsulinemia as achieved by an oral glucose tolerance test ( OGTT ) . Fourteen patients with essential hypertension ( mean age , 46 years ; average blood pressure ( BP ) , 151/96 mm Hg ) were studied . After a 1 week run-in period on their usual diet they entered a r and omized double-blind crossover study of a week of low ( 10 mmol/day ) vs a week of high ( 350 mmol/day ) sodium intake . On the last day of each diet they underwent a st and ard 2-h OGTT . Blood and urines were taken hourly and segmental tubular sodium h and ling was assessed by the endogenous lithium clearance . The results demonstrate that the plasma insulin and glucose response to a short-term oral glucose load were not influenced significantly by the changes in dietary sodium intake . However , the glucose load was associated with marked renal sodium retention in the absence of any change in systemic BP . The reduction in renal sodium excretion was independent of circulating aldosterone but appeared to be due to an increase in renal distal tubular re-absorption The object of the study was to evaluate blood pressure , insulin and glucose metabolism , and serum lipids in hypertensive patients , during 8 weeks on a moderately salt-restricted diet . A double-blind , cross-over study was conducted with hypertensive patients following a moderately salt-restricted diet . Patients were r and omised to sodium capsules in one period and placebo capsules during the other period . After a 1-month run-in period , 13 males and three females with mild to moderate essential hypertension ( mean age 50 years ) complied with a salt-reduced diet . They were r and omized to a salt-supplemented group ( 5 capsules of 10 mmol sodium per capsule ) or a salt reduced diet group ( 5 capsules of placebo ) with cross-over after 8 weeks . Serum insulin , insulin C-peptide , and glucose were measured , fasting and 30 min after a 75-g glucose load . Serum lipids and lipoproteins constituting an atherogenic index were measured , along with blood pressure and 24-h urine excretion of sodium and chloride . Non-significant reductions of systolic and diastolic blood pressure ( 4 mmHg , p = 0.06 , and 2 mmHg , p = 0.13 , respectively ) were observed during the reduced-salt period . The changes observed for fasting insulin , insulin C-peptide , glucose , serum lipids and the atherogenic index were also non-significant . It is concluded that moderate salt restriction seems not to adversely influence insulin resistance or serum lipids in hypertensive patients To examine the effects of sodium intake on insulin sensitivity , we performed euglycemic insulin clamp studies ( 40 mU.m-2.min-1 ) in eight healthy normotensive nondiabetic white males ( age = 36 + /- 5 yr ; wt = 66 + /- 3 kg ) after 5 days on high ( 200 meq/day)- and low ( 10 meq/day)-sodium diets administered in r and om order . High sodium intake was associated with significantly greater urinary sodium excretion ( 160 + /- 7 vs. 8 + /- 2 meq/day ; P < 0.0001 ) , suppression of plasma aldosterone ( 7 + /- 3 vs. 38 + /- 6 ng/dl ; P < 0.001 ) and renin ( 1.5 + /- 0.2 vs. 6.0 + /- 0.9 ng.ml-1.h-1 ; P < 0.005 ) levels , but no change in blood pressure ( 116 + /- 3/63 + /- 2 vs. 114 + /- 3/64 + /- 2 mmHg ; P = not significant ) . The rate of glucose infusion during the clamp was significantly reduced during the high- vs. low-sodium diet ( 279 + /- 19 vs. 334 + /- 24 mg.m-2.min-1 ; P < 0.01 ) . This impairment in insulin sensitivity was not related to changes in serum potassium , epinephrine , norepinephrine , cortisol , or growth hormone but was highly correlated with an increment in circulating free fatty acid levels during high sodium intake ( r = 0.82 , P < 0.05 ) . These data suggest that 1 ) high sodium intake may exacerbate insulin resistance by increasing circulating free fatty acids , and 2 ) differences in sodium intake may influence measures of insulin sensitivity in other disease states Previous investigations examining techniques to estimate sodium intake in free-living persons failed to consider a varying intake or were not conducted under circumstances in which the intake was actually known . To examine the utility of 24-hour and nocturnal urine collection s as estimation of sodium intake under such conditions , we studied 43 white and black men and women ingesting a known sodium intake for 10 days that was r and omly varied daily , with a mean intake of 150/+ 2SD ( range , 50 to 250/ ) . The mean 24-hour sodium excretion ( UNaV ) per day was 141/while the mean sodium intake was 151/. On a r and omly selected day , both nocturnal and 24-hour UNaV estimated that day 's sodium intake reasonably well ( r = 0.55 ) . A stepwise regression showed that including consideration of age and blood pressure improved the correlation ( r = 0.70 ) . However , to estimate mean sodium intake accurately for the entire 10 days , the average of several 24-hour collection s was required . Nine collection s were optimal ( r = 0.75 ) . Nocturnal specimens were not helpful ; the average of all 10 collection s correlated weakly ( r = 0.30 ) with sodium intake . These data sugj.est that to estimate mean sodium intake accurately in free-living persons , only 24-hour collection s are useful , although nocturnal collection s arc helpful in evaluating compliance with low sodium intake . ( Hypertension 4 : 805–808 , 1982 This study investigated whether the change of glycemic response to oral glucose loading with an increase of dietary NaCl intake is different between salt-sensitive and salt-resistant groups , or whether it is related to glucose tolerance on a low NaCl diet independent of salt sensitivity . The plasma glucose and insulin response to 75 g oral glucose intake was assessed on low ( 34 mmol/day ) and high ( 342 mmol/day ) NaCl diets in 31 patients with essential hypertension , and the area under the curve for both variables ( AUCglu and AUCins ) was calculated . The data on the high NaCl diet were corrected for change in hematocrit . The percentage change in systolic , diastolic , and mean blood pressure between the two diets was defined as the salt sensitivity index ( SSI ) for systolic blood pressure ( SSISBP ) , diastolic blood pressure ( SSIDBP ) , and mean blood pressure ( SSIMBP ) , respectively . The mean values of both AUCglu and AUCins decreased significantly with increase of NaCl intake ; however , there was no significant correlation between SSI ( SSISBP , SSIDBP , or SSIMBP ) and the percentage changes in AUCglu and AUCins . Meanwhile , the percentage changes in AUCglu and AUCins significantly correlated with the respective values of AUCglu and AUCins on the low NaCl diet . These results suggest that extreme NaCl restriction may deteriorate glucose metabolism in hypertensive patients , especially in those with diabetes mellitus or impaired glucose tolerance 1 . The aim of this study was to determine the effects of high ( 220 mmol/day ) and low ( 40 mmol/day ) salt intake for 6 days on blood pressure , leg blood flow and insulin sensitivity in 18 healthy normotensive subjects . 2 . Twenty-four-hour ambulatory blood pressure was measured at baseline , during salt-loading and salt-depletion . Insulin sensitivity was determined by a two-step euglycaemic-hyperinsulinaemic clamp ( low and high insulin infusion rates : 40 and 600 m-unit.min-1.m-2 respectively ) and leg blood flow by plethysmography . 3 . Salt-loading result ed in changes in weight [ change between salt-loading and salt-restriction : delta=+0.45 ( S.D. + /-0.69 ) kg , P=0.015 ] , plasma renin [ delta=-11.5 ( S.D.+/-12.9 ) micro-units/l , P=0.001 ] and urinary noradrenaline [ delta=-8.6 ( S.D. + /-18.7 ) nmol/mmol creatinine , P=0.05 ] . There were borderline significant increases in 24-h systolic blood pressure [ delta=+5.8 ( S. D.+/-14.2 ) mmHg , P=0.06 ] and plasma volume [ delta=+0.29 ( S.D.+/-0 . 67 ) litres , P=0.08 ] . 4 . Insulin sensitivity was similar in both salt states . Geometric mean metabolic clearance rate of low-dose insulin : low salt , 5.13 ( S.D.x//1.35 ) dl/min ; high salt , 4.94 ( S.D.x//1.37 ) dl/min , P=1.0 . Geometric mean metabolic clearance rate of high-dose insulin : low salt , 9.68 dl/min ( S.D.x//1.30 ) ; high salt , 9.68 ( S.D. x//1.27 ) dl/min , P=0.69 . 5 . Leg blood flow response to high-dose insulin on high salt increased significantly compared with low salt . Percentage change of blood flow on low salt , delta=+36.6 ( S.D.+/-22 . 9)% versus high salt , delta=+66.8 (S.D.+/-52.2)% , P=0.03 . 6 . There were no significant relationships between salt-related changes in limb blood flow and changes in insulin sensitivity at either insulin infusion rate . 7 . We conclude that salt-loading , despite changing body weight , the renin-angiotensin-aldosterone system , urinary noradrenaline and the leg blood flow response to insulin , has no significant effect on insulin sensitivity . Salt-loading causes dissociated effects on insulin-induced vasodilatation and glucose disposal Objective Homeostasis Model Assessment ( HOMA index ) is predictive of insulin sensitivity in normal and diabetic patients . This study was design ed to see if insulin resistance in hypertensives , measured using the HOMA index , differs , based on salt sensitivity , renin status and sodium intake . Methods Fasting insulin and glucose were determined in subsets of 426 essential hypertensives , and normotensives . HOMA was calculated as fasting glucose ( mmol ) × fasting insulin (μU/ml)/22.5 . Results Four hundred and twenty-six essential hypertensives and normotensives from four HERMES centers form the basis of this report . There was no difference in the HOMA index between hypertensives and normotensives ( P = 0.291 ) or between hypertensives grouped according to blood pressure salt sensitivity ( P = 0.153 ) . However , when essential hypertensives were subgrouped by renin status , the low-renin group had significantly lower ( P < 0.01 ) HOMA index than the normal/high-renin group . When normal/high-renin group was divided into modulators and non-modulators , the non-modulators had significantly higher HOMA index ( P < 0.001 ) than other hypertensive subsets . The effect of sodium intake on the HOMA index was significant only for non-modulators ( P < 0.002 ) , with salt restriction increasing insulin resistance . Conclusion Insulin sensitivity differs among subsets of essential hypertension , non-modulators being most insulin resistant and the low-renin subset insulin sensitive . Salt restriction might have an adverse effect on insulin sensitivity in non-modulators . The reduction in cardiovascular risk seen in low-renin hypertensives may be related to their increased insulin sensitivity ; in contrast , the clustering of cardiovascular risk factors seen in non-modulators may be due to increased insulin resistance Objective . Previous studies , mainly evaluating short-term very low salt diets , suggest that salt restriction may influence glucose and insulin metabolism , catecholamines , renin , aldosterone , and lipid levels adversely . The authors wanted to explore whether sodium restriction for eight weeks influenced insulin secretion unfavourably , and evaluate the efficacy and safety of such treatment also in terms of other parameters important in the management of hypertensive patients . Design . A double-blind r and omized controlled parallel group design ed trial . All participants received dietary advice aim ed at a moderate salt-restricted diet . Half of the participants received salt capsules , the others received identical placebo capsules . Setting . General practice . Subjects . Forty-six hypertensive patients inadequately controlled by drug treatment . Main outcome measures . Fasting serum insulin C-peptide and glucose and levels of these measures after oral glucose , blood pressure , serum aldosterone and lipids , peripheral resistance , and skin conductance . Results . Salt restriction did not influence glucose and insulin metabolism , aldosterone , or lipid levels adversely . We observed better blood pressure regulation in the low salt group than in the high salt group , with a systolic and diastolic blood pressure difference of 5/5 mmHg after eight weeks . The difference was only statistically significant for diastolic blood pressure , p 0.02 . Conclusion . This study revealed a modest diastolic blood pressure reducing effect of moderate sodium restriction . This reduction was obtained without any apparent unfavourable side effects such as increased insulin secretion , impaired glucose tolerance or dyslipidaemia |
13,564 | 22,239,747 | Our study quantifies the magnitude of analgesic treatment disparities in subgroups of minorities .
The treatment gap does not appear to be closing with time or existing policy initiatives . | BACKGROUND The recent Institute of Medicine Report assessing the state of pain care in the United States acknowledged the lack of consistent data to describe the nature and magnitude of unrelieved pain and identify sub population s with disproportionate burdens .
OBJECTIVES We synthesized 20 years of cumulative evidence on racial/ethnic disparities in analgesic treatment for pain in the United States . | INTRODUCTION Healthy People 2010 seeks to eliminate racial and ethnic disparities in health care ; however , disparities due to age and race have been described in emergency department pain treatment . Although pain is a common patient complaint in emergency departments , many people receive no analgesia . This study examined the influence of patient and provider characteristics on ED and discharge analgesia and opioid prescribing practice s. METHODS This descriptive study used chart review of selected variables from ED patients 18 years and older who presented with musculoskeletal pain and were treated by core ED faculty . Logistic regression analyses were performed to determine whether analgesia- and opioid-prescribing disparities existed and were influenced by patient and provider characteristics . RESULTS A total of 868 patient records were examined . Physician characteristics and wide variation in practice were the only sources of disparities in the prescription of analgesics in the emergency department , but patient characteristics including race , age , chronic pain , and trauma influenced prescription of ED opioids and discharge analgesics . No gender or financial status disparities were found . Fewer opioids and discharge analgesics were prescribed for black patients than for white patients . Younger patients , those with trauma , and those with chronic pain received more opioids and discharge analgesics compared with older patients and those without trauma or chronic pain . Providers who completed emergency medicine residencies and had fewer than 3 years ' experience prescribed more analgesics in the emergency department . DISCUSSION Pain management in our emergency department is widely variable , with some disparities based on patient and physician characteristics . Multicenter prospect i ve studies are needed to vali date these findings and examine knowledge and attitude development about pain and its management . Protocol s for nurse-initiated analgesia may help improve and st and ardize ED pain care Context Studies documenting racial/ethnic disparities in health care frequently implicate physicians ’ unconscious biases . No study to date has measured physicians ’ unconscious racial bias to test whether this predicts physicians ’ clinical decisions . Objective To test whether physicians show implicit race bias and whether the magnitude of such bias predicts thrombolysis recommendations for black and white patients with acute coronary syndromes . Design , Setting , and Participants An internet-based tool comprising a clinical vignette of a patient presenting to the emergency department with an acute coronary syndrome , followed by a question naire and three Implicit Association Tests ( IATs ) . Study invitations were e-mailed to all internal medicine and emergency medicine residents at four academic medical centers in Atlanta and Boston ; 287 completed the study , met inclusion criteria , and were r and omized to either a black or white vignette patient . Main Outcome Measures IAT scores ( normal continuous variable ) measuring physicians ’ implicit race preference and perceptions of cooperativeness . Physicians ’ attribution of symptoms to coronary artery disease for vignette patients with r and omly assigned race , and their decisions about thrombolysis . Assessment of physicians ’ explicit racial biases by question naire . Results Physicians reported no explicit preference for white versus black patients or differences in perceived cooperativeness . In contrast , IATs revealed implicit preference favoring white Americans ( mean IAT score = 0.36 , P < .001 , one- sample t test ) and implicit stereotypes of black Americans as less cooperative with medical procedures ( mean IAT score 0.22 , P < .001 ) , and less cooperative generally ( mean IAT score 0.30 , P < .001 ) . As physicians ’ prowhite implicit bias increased , so did their likelihood of treating white patients and not treating black patients with thrombolysis ( P = .009 ) . Conclusions This study represents the first evidence of unconscious ( implicit ) race bias among physicians , its dissociation from conscious ( explicit ) bias , and its predictive validity . Results suggest that physicians ’ unconscious biases may contribute to racial/ethnic disparities in use of medical procedures such as thrombolysis for myocardial infa rct ion & NA ; Previous retrospective studies have suggested that patient demographics may influence analgesic administration . These studies have not taken physicians ’ impression of patient pain into account . This prospect i ve study investigates the influence of ( i ) physician impression of the degree of pain and ( ii ) patient demographics on the use of analgesic . A convenience sample of adults with non‐traumatic lower back pain was studied . Possible predictors of analgesic administration included physician pain scores ( assessed by visual analogue scale ) , patient ethnicity , gender , age , and insurance . These variables were tested individually and then using logistic regression . For the total of 91 patients enrolled , only physician pain scale was found to be associated with analgesic use . Median scores were 68 mm ( interquartile range=62–80 mm ) for those receiving treatment versus 48 mm ( interquartile range=30–58 mm ) for those who did not ( P<0.001 ) . This study therefore suggests that physician impression of patient pain rather than patient demographics influences analgesic use OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity BACKGROUND We have observed that many black and Hispanic patients receiving palliative care at a major urban teaching hospital are unable to obtain prescribed opioids from their neighborhood pharmacies . In this study , we investigated the availability of commonly prescribed opioids in New York City pharmacies . METHODS We surveyed a r and omly selected sample of 30 percent of New York City pharmacies to obtain information about their stock of opioids . For each pharmacy , U.S. Census estimates for 1997 were used to determine the racial and ethnic composition of the neighborhood ( defined as the area within a 0.4-km [ 0.25-mile ] radius of the pharmacy ) and the proportion of residents who were more than 65 years old . Data on robberies , burglaries , and arrests involving illicit drugs in 1997 were obtained for the precinct in which each pharmacy was located . We used a generalized linear model to examine the relation between the racial or ethnic composition of neighborhoods and the opioid supplies of pharmacies , while controlling for the proportion of elderly persons at the census-block level and for crime rates at the precinct level . RESULTS Pharmacists representing 347 of 431 eligible pharmacies ( 81 percent ) responded to the survey . A total of 176 pharmacies ( 51 percent ) did not have sufficient supplies of opioids to treat patients with severe pain . Only 25 percent of pharmacies in predominantly nonwhite neighborhoods ( those in which less than 40 percent of residents were white ) had opioid supplies that were sufficient to treat patients in severe pain , as compared with 72 percent of pharmacies in predominantly white neighborhoods ( those in which at least 80 percent of residents were white ) ( P<0.001 ) . CONCLUSIONS Pharmacies in predominantly nonwhite neighborhoods of New York City do not stock sufficient medications to treat patients with severe pain adequately OBJECTIVE To describe the patterns of opioid prescribing and the factors associated with reductions in the potency of patients ' analgesic medications at the time of hospital discharge . DESIGN Prospect i ve cohort . SETTING Two hundred forty-four patients ( 171 surgical and 73 nonsurgical ) hospitalized in an urban academic medical center who have experienced moderate or severe pain and who are taking opioid analgesics prior to discharge . OUTCOME Step-down ( or reduction ) in the potency of patients ' analgesic medication at the time of discharge . A step-down is defined as the analgesic medication that a patient is prescribed for outpatient analgesia at the time of discharge being less potent then the last pain medication administered to that patient just prior to hospital discharge . RESULTS Thirty-three percent of all patients had reductions in the potency of their opioid pain medication at the time of discharge ( 36 % for surgical and 26 % for nonsurgical patients ) . For nonsurgical patients , we found a trend toward Hispanic ethnicity being an independent risk factor for having a step-down in analgesic potency at discharge ( odds ratio [ OR ] : 3.7 , 95 % confidence interval [ CI ] : 0.9 - 14.9 ) . CONCLUSION Physicians frequently reduce the potency of hospitalized patients ' pain medications at discharge and Hispanic patients may be at increased risk of this occurring . Further research is needed to determine if the reductions in analgesic potency we observed are associated with poor posthospital pain outcomes UNLABELLED Little is known about physical barriers to adequate pain treatment for minorities . This investigation explored sociodemographic determinants of pain medication availability in Michigan pharmacies . A cross-sectional survey-based study with census data and data provided by Michigan community retail pharmacists was design ed . Sufficient opioid analgesic supplies was defined as stocking at least one long-acting , short-acting , and combination opioid analgesic . Pharmacies located in minority ( < or=70 % minority residents ) and white ( > or=70 % white residents ) zip code areas were r and omly selected by using a 2-stage sampling selection process ( response rate , 80 % ) . For the 190 pharmacies surveyed , most were located in white areas ( 51.6 % ) and had sufficient supplies ( 84.1 % ) . After accounting for zip code median age and stratifying by income , pharmacies in white areas ( odds ratio , 13.36 high income vs 54.42 low income ) and noncorporate pharmacies ( odds ratio , 24.92 high income vs 3.61 low income ) were more likely to have sufficient opioid analgesic supplies ( P < .005 ) . Racial differences in the odds of having a sufficient supply were significantly higher in low income areas when compared with high income areas . Having a pharmacy located near a hospital did not change the availability for opioid analgesics . Persons living in predominantly minority areas experienced significant barriers to accessing pain medication , with greater disparities in low income areas regardless of ethnic composition . Differences were also found on the basis of pharmacy type , suggesting variability in pharmacist 's decision making . PERSPECTIVE Michigan pharmacies in minority zip codes were 52 times less likely to carry sufficient opioid analgesics than pharmacies in white zip codes regardless of income . Lower income areas and corporate pharmacies were less likely to carry sufficient opioid analgesics . This study illustrates barriers to pain care and has public health implication UNLABELLED This study investigated the association between effectiveness of ED pain treatment and race of patients , race of providers , and the concordance of patient and provider race , with a prospect i ve , multicenter study of patients presenting to 1 of 20 US and Canadian EDs with moderate to severe pain . Primary outcome is a 2-point or greater reduction in pain intensity , measured with an 11-point verbal scale , considered the minimum clinical ly important reduction in pain intensity . A total of 776 patients were enrolled . The sample included 57 % female , 44 % white , 26 % black , and 26 % Hispanic . The physician was white in 85 % of encounters . Arrival pain score ( adjusted odds ratio , 1.14 ; 95 % CI 1.06 , 1.24 ) , receipt of any ED analgesia ( 1.59 ; 95 % CI 1.17 , 2.17 ) , and physician nonwhite race ( 1.68 ; 95 % CI 1.10 , 2.55 ) were significant predictors of clinical ly significant reduction in pain intensity in multivariate analysis . Nonwhite physicians achieved better pain control without using more analgesics . Future research should explore the determinants of this difference in patient response to pain treatment related to provider race including provider characteristics and training that were not measured in this study . This study provided no evidence supporting an effect of racial concordance on the primary outcome . PERSPECTIVE This article presents analysis of predictors of clinical ly important reduction in pain intensity among emergency department patients , finding nonwhite physicians achieving better pain relief with less analgesia . This finding should encourage research ers to investigate elements of the therapeutic relationship that may be enhanced to achieve better pain relief for patients OBJECTIVES The objective was to test the hypothesis that African American and Hispanic patients are less likely to receive analgesics than white patients in two academic urban emergency departments ( EDs ) . METHODS This was a prospect i ve observational study of a convenience sample of patients with long-bone fractures from April 2002 to November 2006 in two academic urban EDs . Eligibility criteria were age 18 - 55 years , isolated long-bone fracture , and race and ethnicity ( Hispanic , African American , and white ) . The primary outcome was receipt of analgesics ; secondary outcomes included receipt of opioids , dose , route , time to first analgesic , and change in pain . Logistic regression was used to adjust the risk of receiving analgesics for patients ' initial rating of pain and demographic characteristics . RESULTS Of 1,239 patients with suspected long-bone fractures , 345 patients were eligible : 177 ( 51 % ) were Hispanic , 98 ( 28 % ) were African American , and 70 ( 20 % ) were white . Administration of analgesics was not associated with race or ethnicity . Sixteen percent ( 95 % confidence interval [ CI ] = 11 % to 22 % ) of Hispanic , 15 % ( 95 % CI = 10 % to 24 % ) of African American , and 14 % ( 95 % CI = 8 % to 24 % ) of white patients did not receive any analgesics . Seventy-four percent of Hispanic ( 95 % CI = 67 % to 80 % ) , 66 % of African American ( 95 % CI = 57 % to 75 % ) , and 69 % ( 95 % CI = 57 % to 78 % ) of white patients received opioid analgesics . After adjustment for covariates , there was no evidence of an association between receipt of analgesics or opioid analgesics and the race or ethnicity of the patients . There were no significant differences in time to treatment , dose , route , or change in pain . CONCLUSIONS Receipt of analgesics for pain from long-bone fractures was not associated with patient race or ethnicity in two academic urban EDs OBJECTIVES The authors assessed the effect of emergency department ( ED ) crowding on the nontreatment and delay in treatment for analgesia in patients who had acute abdominal pain . METHODS This was a secondary analysis of prospect ively enrolled nonpregnant adult patients presenting to an urban teaching ED with abdominal pain during a 9-month period . Each patient had four vali date d crowding measures assigned at triage . Main outcomes were the administration of and delays in time to analgesia . A delay was defined as waiting more than 1 hour for analgesia . Relative risk ( RR ) regression was used to test the effects of crowding on outcomes . RESULTS A total of 976 abdominal pain patients ( mean [ + /-st and ard deviation ] age = 41 [ + /-16.6 ] years ; 65 % female , 62 % black ) were enrolled , of whom 649 ( 67 % ) received any analgesia . Of those treated , 457 ( 70 % ) experienced a delay in analgesia from triage , and 320 ( 49 % ) experienced a delay in analgesia after room placement . After adjusting for possible confounders of the ED administration of analgesia ( age , sex , race , triage class , severe pain , final diagnosis of either abdominal pain not otherwise specified or gastroenteritis ) , increasing delays in time to analgesia from triage were independently associated with all four crowding measures , comparing the lowest to the highest quartile of crowding ( total patient-care hours RR = 1.54 , 95 % confidence interval [ CI ] = 1.32 to 1.80 ; occupancy rate RR = 1.64 , 95 % CI = 1.42 to 1.91 ; inpatient number RR = 1.57 , 95 % CI = 1.36 to 1.81 ; and waiting room number RR = 1.53 , 95 % CI = 1.31 to 1.77 ) . Crowding measures were not associated with the failure to treat with analgesia . CONCLUSIONS Emergency department crowding is associated with delays in analgesic treatment from the time of triage in patients presenting with acute abdominal pain OBJECTIVES Previous studies have reported that pain is undertreated in the emergency department ( ED ) , but few physician-dependent risk factors have been identified . In this study , the authors determine whether pain treatment and relief in ED patients are negatively associated with the physician 's perception of whether the patient was exaggerating symptoms , and with the patient and physician 's perceptions of the interaction between them , as well as whether demographic characteristics were associated with these perceptions . METHODS This was a prospect i ve observational study of patients who were undergoing treatment for painful disorders in the ED . Before treatment for pain , patients were asked to complete a 100-mm visual analog scale ( VAS ) describing their pain . Demographic information and pain treatments administered were recorded . Patients completed a second pain VAS before discharge from the ED . Patients were then asked to complete three queries describing their perception of their interaction with the physician . After the patient had left the department , the patient 's physician was asked to complete a query describing his or her perception of the interaction and to complete a VAS describing how likely it was that the patient was exaggerating symptoms to obtain pain medicines for nonmedical purpose s. RESULTS There were 1,695 patients enrolled in the study ; 32 patients were excluded because of missing or incomplete data , leaving 1,663 for analysis . Of these patients , 71.9 % received a pain medication while in the ED . There was no association between the physician 's VAS for perceived exaggeration of symptoms , the queries describing physician-patient interactions , and patient ethnicity and whether patients received pain treatment in the ED . There was a negative correlation between the physician 's VAS for perceived exaggeration of symptoms and the change in the patient 's pre- and posttreatment pain VAS scores . The physician 's VAS score for perceived exaggeration of symptoms was higher among Native American patients than among other ethnic groups ( p < or = 0.001 ) . The patient and physician queries rating their interaction show a decreased absolute reduction of VAS pain scores ( p > or = 0.001 ) and a reduction in the number of patients having at least a 50 % reduction in their pain VAS score when interactions were rated " bad " and " very bad " ( p < or = 0.001 ) . CONCLUSIONS The physician 's perception of whether a patient was exaggerating symptoms was associated with the patient 's ethnic background and with both the physician 's and patient 's perception of their interaction . These perceptions were negatively associated with the achievement of pain relief and the change in the patient 's pain VAS scores , but not with whether a patient was treated with a pain medication OBJECTIVE To determine the efficacy of pain scores in improving pain management practice s for trauma patients in the emergency department ( ED ) . METHODS A prospect i ve , observational study of analgesic administration to trauma patients was conducted over a nine-week period following educational intervention and introduction of verbal pain scores ( VPSs ) . All ED nursing and physician staff in an urban Level I trauma center were trained to use the 0 - 10 VPS . Patients younger than 12 years old , having a Glasgow Coma Scale score ( GCS ) < 8 , or requiring intubation were excluded from analysis . Demographics , mechanism of injury , vital signs , pain scores , and analgesic data were extracted from a computerized ED data base and patients ' records . The staff was blinded to the ongoing study . RESULTS There were 150 patients studied ( 183 consecutive trauma patients seen ; 33 patients excluded per criteria ) . Pain scores were documented for 73 % of the patients . Overall , 53 % ( 95 % confidence interval [ CI ] = 45 % to 61 % ) of the patients received analgesics in the ED . Of the patients who had pain scores documented , 60 % ( 95 % CI = 51 % to 69 % ) received analgesics , whereas 33 % ( 95 % CI = 18 % to 47 % ) of the patients without pain scores received analgesics . No patient with a VPS < 4 received analgesics , whereas 72 % of patients with a VPS > 4 and 82 % with a VPS > 7 received analgesics . Mean time to analgesic administration was 68 minutes ( 95 % CI = 49 to 87 ) . CONCLUSIONS Pain assessment using VPS increased the likelihood of analgesic administration to trauma patients with higher pain scores in the ED BACKGROUND Cyclooxygenase-2-selective inhibitors ( coxibs ) have been widely adopted , despite study findings suggesting that they are cost-effective only in certain population s. OBJECTIVE This study was conducted to identify factors that were associated with the selection of coxibs rather than nonselective NSAIDs in the period before the emergence of safety concerns in 2004 . METHODS This was a retrospective cohort analysis of a 15 % r and om sample of Kansas Medicaid beneficiaries aged > 60 years that used inpatient , outpatient , and prescription cl aims data . Subjects were included if they received a prescription for a coxib or nonselective NSAID after a 6-month period without an anti-inflammatory prescription cl aim and if they underwent at least 90 days of follow-up after the initial prescription . Using 2 previously published models ( Dominick et al and Shaya and Blume ) , we analyzed the impact of factors potentially associated with the preferential selection of a coxib , including age , sex , race , history of upper gastrointestinal disease , chronic or acute use , and recent anticoagulant or corticosteroid therapy . RESULTS Study subjects ( N = 853 ) were predominantly female ( 78.8 % ) and white ( 80.4 % ) , and had a mean age of 78 years ; 65.1 % were prescribed a coxib and 34.9 % were prescribed a nonselective NSAID . In bivariate analyses , coxib users were more likely than nonselective NSAID users to be white ( 83.2 % vs 75.3 % , respectively ; P < 0.05 ) , to be prescribed chronic rather than acute therapy ( 81.8 % vs 58.7 % ; P < 0.001 ) , and to have a concomitant prescription for warfarin ( 11.2 % vs 5.7 % ; P < 0.05 ) . Multivariate analyses indicated significance for the same predictors of coxib use : chronic versus acute therapy ( Dominick model : adjusted odds ratio [ AOR ] = 3.39 ; 95 % CI , 2.43 - 4.74 ; Shaya model : AOR = 3.39 ; 95 % CI , 2.43 - 4.74 ) ; concomitant anticoagulant therapy ( Dominick model : AOR = 2.16 ; 95 % CI , 1.18 - 3.97 ; Shaya model : AOR = 2.31 ; 95 % CI , 0.28 - 0.83 ) ; and black race ( Dominick model : AOR = 0.48 ; 95 % CI , 0.28 - 0.83 ; Shaya model : AOR = 0.49 ; 95 % CI , 0.28 - 0.84 ) . The most commonly prescribed nonselective NSAIDs were ibuprofen ( 14.3 % of all subjects ) and naproxen ( 6.6 % of all subjects ) ; the most commonly prescribed coxibs were rofecoxib ( 36.5 % ) and celecoxib ( 28.5 % ) . CONCLUSIONS In this study in an older population , coxibs constituted almost two thirds of all initial anti-inflammatory prescriptions . The prescription of a coxib was influenced by concomitant anticoagulant use and chronic use . Blacks were significantly more likely than whites to receive a nonselective NSAID . Although coxib use has been affected by the association with cardiovascular risk that emerged after the period of this study , rational drug selection and reduction of racial/ethnic disparities remain important targets for improved quality of care OBJECTIVES Oligoanalgesia for acute abdominal pain historically has been attributed to the provider 's fear of masking serious underlying pathology . The authors assessed whether a gender disparity exists in the administration of analgesia for acute abdominal pain . METHODS This was a prospect i ve cohort study of consecutive nonpregnant adults with acute nontraumatic abdominal pain of less than 72 hours ' duration who presented to an urban emergency department ( ED ) from April 5 , 2004 , to January 4 , 2005 . The main outcome measures were analgesia administration and time to analgesic treatment . St and ard comparative statistics were used . RESULTS Of the 981 patients enrolled ( mean age + /- st and ard deviation [ SD ] 41 + /- 17 years ; 65 % female ) , 62 % received any analgesic treatment . Men and women had similar mean pain scores , but women were less likely to receive any analgesia ( 60 % vs. 67 % , difference 7 % , 95 % confidence interval [ CI ] = 1.1 % to 13.6 % ) and less likely to receive opiates ( 45 % vs. 56 % , difference 11 % , 95 % CI = 4.1 % to 17.1 % ) . These differences persisted when gender-specific diagnoses were excluded ( 47 % vs. 56 % , difference 9 % , 95 % CI = 2.5 % to 16.2 % ) . After controlling for age , race , triage class , and pain score , women were still 13 % to 25 % less likely than men to receive opioid analgesia . There was no gender difference in the receipt of nonopioid analgesia . Women waited longer to receive their analgesia ( median time 65 minutes vs. 49 minutes , difference 16 minutes , 95 % CI = 3.5 to 33 minutes ) . CONCLUSIONS Gender bias is a possible explanation for oligoanalgesia in women who present to the ED with acute abdominal pain . St and ardized protocol s for analgesic administration may ameliorate this discrepancy |
13,565 | 27,086,572 | Limited subgroup analyses suggested that the effect of aspirin on major adverse cardiovascular events differed by baseline cardiovascular disease risk , medication compliance and sex ( P for interaction for all > 0.05).There was no significant reduction in the risk of myocardial infa rct ion , coronary heart disease , stroke , cardiovascular mortality or all-cause mortality .
Aspirin significantly reduced the risk of myocardial infa rct ion for a treatment duration of ≤ 5 years .
There was an increase in risk of major or gastrointestinal bleeding events , but estimates were imprecise and not significant . | AIMS To evaluate the benefits and harms of aspirin for the primary prevention of cardiovascular disease and all-cause mortality events in people with diabetes by conducting a systematic review and meta- analysis . | Background —Considerable evidence implicates the proinflammatory cytokine CD40 lig and ( CD40L ) in atherosclerosis and accumulating data link type 1 and 2 diabetes , conditions associated with accelerated atherosclerosis , to inflammation . This study therefore evaluated the hypothesis that diabetic patients have elevated plasma levels of soluble CD40L ( sCD40L ) and that treatment with the insulin-sensitizing thiazolidinediones lowers this index of inflammation . Methods and Results —Subjects with type 1 ( n=49 ) or type 2 diabetes ( n=48 ) had higher ( P < 0.001 ) sCD40L plasma levels ( 6.56±3.27 and 6.67±2.90 ng/mL , respectively ) compared with age-matched control groups ( 1.40±2.21 and 1.32±2.68 ng/mL , respectively ) . Multiple regression analysis demonstrated a significant ( P < 0.001 ) association between plasma sCD40L and type 1 as well as type 2 diabetes , independent of total cholesterol , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol , triglycerides , blood pressure , body mass index , gender , C-reactive protein , and soluble intracellular adhesion molecule-1 . Furthermore , in a pilot study , administration of troglitazone ( 12 weeks , 600 mg/day ) , but not placebo , to type 2 diabetics ( n=68 ) significantly ( P < 0.001 ) diminished sCD40L plasma levels by 29 % . The thiazolidinedione lowered plasma sCD40L in type 2 diabetic patients with long-st and ing disease ( > 3 years ) with or without macrovascular complications ( −34 % and −29 % , respectively ) as well as in type 2 diabetic patients with more recent ( <3 years ) onset of the disease ( −27 % ; all P < 0.05 ) . Conclusions —This study provides new evidence that individuals with type 1 or 2 diabetes have a proinflammatory state as indicated by elevated levels of plasma sCD40L . Troglitazone treatment of type 2 diabetic patients diminishes sCD40L levels , suggesting a novel antiinflammatory mechanism for limiting diabetes-associated arterial disease Reduced effectiveness of the most common antiplatelet drug , acetylsalicylic acid ( ASA , aspirin ) , in diabetes mellitus has been associated with a lowered platelet sensitivity to ASA and related to glycemic control in diabetic patients . Our objectives were ( a ) to monitor the chemical background of how chronic hyperglycemia affects platelet response to ASA in diabetes and ( b ) to study a chemical competition between the amount of bound acetyl residues and the extent of protein glycation in blood platelets . Using whole-blood impedance aggregometry and platelet function analyzer ( PFA-100 ) we observed a reduced platelet response to ASA in diabetic patients ( 14 % vs. 79 % for PFA-100 collagen-epinephrine occlusion time ) and an association between the index of glycemic control and platelet refractoriness to ASA ( rS=−0.378 ) . Impaired platelet response to ASA was related to enhanced platelet protein glycation ( 3.6±0.4 in diabetes vs. 2.3±0.4 µmol fructosamine/µg protein in control ) and reduced incorporation of acetyl residue into proteins of platelets from diabetic patients ( 47.4±2.0 in control vs. 33.1±0.7 µmol acetyl/µg protein in diabetic subjects ) . Incubation of blood platelets with increasing concentrations of glucose and ASA under in vitro conditions led to excessive modification in protein amino groups : glucose and ASA competed with each other in the course of nonenzymatic modifications , glycosylation , or acetylation , and their contributions to the occupancy of protein amino groups ( R2=0.22 for glucose , R2=0.43 for ASA ) were dependent upon the concentrations of glucose and ASA . Overall the effects of high glucose and high ASA on the overall occupancy of protein free amino groups are not additive . While at higher concentrations ASA overcomes the effects of hyperglycemia and retards glycation , high glucose makes acetylation less efficient , and therefore the result ant chemical modification becomes greatly reduced . In conclusion , diminished susceptibility of various platelet proteins and receptors on blood platelet membranes to acetylation and high ambient glucose might underlie the apparently differentiated sensitivity of blood platelets to ASA and determine platelet “ insensitivity to aspirin ” in diabetic 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 Observational epidemiological studies suffer from many potential biases , from confounding and from reverse causation , and this limits their ability to robustly identify causal associations . Several high-profile situations exist in which r and omized controlled trials of precisely the same intervention that has been examined in observational studies have produced markedly different findings . In other observational sciences , the use of instrumental variable ( IV ) approaches has been one approach to strengthening causal inferences in non-experimental situations . The use of germline genetic variants that proxy for environmentally modifiable exposures as instruments for these exposures is one form of IV analysis that can be implemented within observational epidemiological studies . The method has been referred to as ' Mendelian r and omization ' , and can be considered as analogous to r and omized controlled trials . This paper outlines Mendelian r and omization , draws parallels with IV methods , provides examples of implementation of the approach and discusses limitations of the approach and some methods for dealing with these OBJECTIVE We investigated in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with type 2 diabetes . RESEARCH DESIGN AND METHODS The Primary Prevention Project ( PPP ) is a r and omized , open trial with a two-by-two factorial design aim ed to investigate low-dose aspirin ( 100 mg/day ) and vitamin E ( 300 mg/day ) in the prevention of cardiovascular events in patients with one or more cardiovascular risk factors . The primary end point was a composite end point of cardiovascular death , stroke , or myocardial infa rct ion . A total of 1,031 people with diabetes in the PPP , aged > /=50 years , without a previous cardiovascular event were enrolled by 316 general practitioners and 14 diabetes outpatient clinics . RESULTS The PPP trial was prematurely stopped ( after a median of 3.7 years ) by the independent data safety and monitoring board because of a consistent benefit of aspirin compared with the control group in a population of 4,495 patients with one or more major cardiovascular risk factors . In diabetic patients , aspirin treatment was associated with a nonsignificant reduction in the main end point ( relative risk [ RR ] = 0.90 , 95 % CI 0.50 - 1.62 ) and in total cardiovascular events ( 0.89 , 0.62 - 1.26 ) and with a nonsignificant increase in cardiovascular deaths ( 1.23 , 0.69 - 2.19 ) . In nondiabetic subjects , RRs for the main end point , total cardiovascular events , and cardiovascular deaths were 0.59 ( 0.37 - 0.94 ) , 0.69 ( 0.53 - 0.90 ) , and 0.32 ( 0.14 - 0.72 ) , respectively . No significant reduction in any of the end points considered could be found with vitamin E in either diabetic or nondiabetic subjects . CONCLUSIONS Our data suggest a lower effect of primary prevention of cardiovascular disease ( CVD ) with low-dose aspirin in diabetic patients as opposed to subjects with other cardiovascular risk factors . If confirmed , these findings might indicate that the antiplatelet effects of aspirin in diabetic patients are overwhelmed by aspirin-insensitive mechanisms of platelet activation and thrombus formation , thus making the balance between benefits and harms of aspirin treatment unfavorable . Further large-scale trials investigating the role of aspirin in the primary prevention of CVD in diabetic patients are urgently needed BACKGROUND Despite treatment , there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals . Inadequate reduction of their blood pressure is a likely cause , but the optimum target blood pressure is not known . The impact of acetylsalicylic acid ( aspirin ) has never been investigated in patients with hypertension . We aim ed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension . METHODS 18790 patients , from 26 countries , aged 50 - 80 years ( mean 61.5 years ) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg ( mean 105 mm Hg ) were r and omly assigned a target diastolic blood pressure . 6264 patients were allocated to the target pressure < or = 90 mm Hg , 6264 to < or = 85 mm Hg , and 6262 to < or = 80 mm Hg . Felodipine was given as baseline therapy with the addition of other agents , according to a five-step regimen . In addition , 9399 patients were r and omly assigned 75 mg/day acetylsalicylic acid ( Bamycor , Astra ) and 9391 patients were assigned placebo . FINDINGS Diastolic blood pressure was reduced by 20.3 mm Hg , 22.3 mm Hg , and 24.3 mm Hg , in the < or = 90 mm Hg , < or = 85 mm Hg , and < or = 80 mm Hg target groups , respectively . The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg ; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg . Further reduction below these blood pressures was safe . In patients with diabetes mellitus there was a 51 % reduction in major cardiovascular events in target group < or = 80 mm Hg compared with target group < or = 90 mm Hg ( p for trend=0.005 ) . Acetylsalicylic acid reduced major cardiovascular events by 15 % ( p=0.03 ) and all myocardial infa rct ion by 36 % ( p=0.002 ) , with no effect on stroke . There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group , and 129 versus 70 non-fatal major bleeds in the two groups , respectively ( p<0.001 ) . INTERPRETATION Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events . The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg . Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infa rct ion . There was no effect on the incidence of stroke or fatal bleeds , but non-fatal major bleeds were twice as common A six year r and omised trial was conducted among 5139 apparently healthy male doctors to see whether 500 mg aspirin daily would reduce the incidence of and mortality from stroke , myocardial infa rct ion , or other vascular conditions . Though total mortality was 10 % lower in the treated than control group , this difference was not statistically significant and chiefly involved diseases other than stroke or myocardial infa rct ion . Likewise , there was no significant difference in the incidence of non-fatal myocardial infa rct ion or stroke — indeed , disabling strokes were somewhat commoner among those allocated aspirin . The lower confidence limit for the effect of aspirin on non-fatal stroke or myocardial infa rct ion , however , was a substantial 25 % reduction . Migraine and certain types of musculoskeletal pain were reported significantly less often in the treated than control group , but as the control group was not given a placebo the relevance of these findings was difficult to assess . There was no apparent reduction in the incidence of cataract in the treated group . The lack of any apparent reduction in disabling stroke or vascular death contrasts with the established value of antiplatelet treatment after occlusive vascular disease Despite multiple interventions to reduce the risk of cardiovascular disease , the majority of people with diabetes develop macrovascular complications , and mortality following myocardial infa rct ion remains unacceptably high [ 1 ] . Antiplatelet agents are used for both the primary and secondary prevention of cardiovascular disease , although current guidelines are not consistent in their recommendation for the use of aspirin in diabetes [ 2 ] . In fact , there is little direct evidence supporting its efficacy in this group of patients . Instead , there is convincing data in the literature to suggest inadequate cardiovascular protection by aspirin in diabetes . In a meta- analysis of 287 r and omised trials , antiplatelet treatment ( aspirin in most studies ) reduced the risk of ischaemic events by 22 % , but the risk reduction in the subgroup with diabetes was only 7 % , which was not statistically significant [ 3 ] . This outcome was mirrored in the Primary Prevention Project trial , which reported that cardiovascular risk reduction with aspirin was marginal and non-significant in the presence of diabetes [ 4 ] . Despite this , there are no published studies specifically design ed to evaluate the clinical efficacy of aspirin in individuals with diabetes , a surprising omission in the era of ‘ evidence based ’ medicine . These findings from clinical trials raise the question as to why there should be a reduction in the clinical efficacy of aspirin in patients with diabetes compared with a nondiabetic population . Diabetes is intrinsically associated with particular biochemical abnormalities that may have the capacity to diminish the effects of aspirin on platelet function and cardiovascular risk — a possibility that has led to the hotly debated concept of aspirin resistance [ 5 , 6 ] . Unfortunately , aspirin resistance suffers from a lack of a st and ardised definition , although now generally thought of as either ( 1 ) reflecting clinical aspirin resistance ( or perhaps , more accurately , treatment failure ) , characterised by the occurrence of a thrombotic episode despite treatment with aspirin ; or ( 2 ) biochemical aspirin resistance where platelet responses persist despite platelet exposure to aspirin . Controversy remains as to the cause of biochemical aspirin resistance , its relevance to clinical outcomes , and the place of aspirin treatment in the management of cardiovascular risk in diabetes patients . All of this highlights the urgent need to underst and the mechanisms that underpin the interactions between diabetes and aspirin , to establish the role of aspirin in particular , and antiplatelet therapy in general , in the amelioration of cardiovascular events in individuals with diabetes . Diabetologia ( 2008 ) 51:385–390 DOI 10.1007/s00125 - 007 - 0898 - OBJECTIVES This report presents information on the effects of aspirin on mortality , the occurrence of cardiovascular events , and the incidence of kidney disease in the patients enrolled in the Early Treatment Diabetic Retinopathy Study ( ETDRS ) . STUDY DESIGN This multicenter , r and omized clinical trial of aspirin vs placebo was sponsored by the National Eye Institute . PATIENTS Patients ( N = 3711 ) were enrolled in 22 clinical centers between April 1980 and July 1985 . Men and women between the ages of 18 and 70 years with a clinical diagnosis of diabetes mellitus were eligible . Approximately 30 % of all patients were considered to have type I diabetes mellitus , 31 % type II , and in 39 % type I or II could not be determined definitely . INTERVENTION Patients were r and omly assigned to aspirin or placebo ( two 325-mg tablets once per day ) . MAIN OUTCOME MEASURES Mortality from all causes was specified as the primary outcome measure for assessing the systemic effects of aspirin . Other outcome variables included cause-specific mortality and cardiovascular events . RESULTS The estimate of relative risk for total mortality for aspirin-treated patients compared with placebo-treated patients for the entire study period was 0.91 ( 99 % confidence interval , 0.75 to 1.11 ) . Larger differences were noted for the occurrence of fatal and nonfatal myocardial infa rct ion ; the estimate of relative risk was 0.83 for the entire follow-up period ( 99 % confidence interval , 0.66 to 1.04 ) . CONCLUSIONS The effects of aspirin on any of the cardiovascular events considered in the ETDRS were not substantially different from the effects observed in other studies that included mainly nondiabetic persons . Furthermore , there was no evidence of harmful effects of aspirin . Aspirin has been recommended previously for persons at risk for cardiovascular disease . The ETDRS results support application of this recommendation to those persons with diabetes at increased risk of cardiovascular disease IMPORTANCE Prevention of atherosclerotic cardiovascular diseases is an important public health priority in Japan due to an aging population . OBJECTIVE To determine whether daily , low-dose aspirin reduces the incidence of cardiovascular events in older Japanese patients with multiple atherosclerotic risk factors . DESIGN , SETTING , AND PARTICIPANTS The Japanese Primary Prevention Project ( JPPP ) was a multicenter , open-label , r and omized , parallel-group trial . Patients ( N = 14,464 ) were aged 60 to 85 years , presenting with hypertension , dyslipidemia , or diabetes mellitus recruited by primary care physicians at 1007 clinics in Japan between March 2005 and June 2007 , and were followed up for up to 6.5 years , with last follow-up in May 2012 . A multidisciplinary expert panel ( blinded to treatment assignments ) adjudicated study outcomes . INTERVENTIONS Patients were r and omized 1:1 to enteric-coated aspirin 100 mg/d or no aspirin in addition to ongoing medications . MAIN OUTCOMES AND MEASURES Composite primary outcome was death from cardiovascular causes ( myocardial infa rct ion , stroke , and other cardiovascular causes ) , nonfatal stroke ( ischemic or hemorrhagic , including undefined cerebrovascular events ) , and nonfatal myocardial infa rct ion . Secondary outcomes included individual end points . RESULTS The study was terminated early by the data monitoring committee after a median follow-up of 5.02 years ( interquartile range , 4.55 - 5.33 ) based on likely futility . In both the aspirin and no aspirin groups , 56 fatal events occurred . Patients with an occurrence of nonfatal stroke totaled 114 in the aspirin group and 108 in the no aspirin group ; of nonfatal myocardial infa rct ion , 20 in the aspirin group and 38 in the no aspirin group ; of undefined cerebrovascular events , 3 in the aspirin group and 5 in the no aspirin group . The 5-year cumulative primary outcome event rate was not significantly different between the groups ( 2.77 % [ 95 % CI , 2.40%-3.20 % ] for aspirin vs 2.96 % [ 95 % CI , 2.58%-3.40 % ] for no aspirin ; hazard ratio [ HR ] , 0.94 [ 95 % CI , 0.77 - 1.15 ] ; P = .54 ) . Aspirin significantly reduced incidence of nonfatal myocardial infa rct ion ( 0.30 [ 95 % CI , 0.19 - 0.47 ] for aspirin vs 0.58 [ 95 % CI , 0.42 - 0.81 ] for no aspirin ; HR , 0.53 [ 95 % CI , 0.31 - 0.91 ] ; P = .02 ) and transient ischemic attack ( 0.26 [ 95 % CI , 0.16 - 0.42 ] for aspirin vs 0.49 [ 95 % CI , 0.35 - 0.69 ] for no aspirin ; HR , 0.57 [ 95 % CI , 0.32 - 0.99 ] ; P = .04 ) , and significantly increased the risk of extracranial hemorrhage requiring transfusion or hospitalization ( 0.86 [ 95 % CI , 0.67 - 1.11 ] for aspirin vs 0.51 [ 95 % CI , 0.37 - 0.72 ] for no aspirin ; HR , 1.85 [ 95 % CI , 1.22 - 2.81 ] ; P = .004 ) . CONCLUSIONS AND RELEVANCE Once-daily , low-dose aspirin did not significantly reduce the risk of the composite outcome of cardiovascular death , nonfatal stroke , and nonfatal myocardial infa rct ion among Japanese patients 60 years or older with atherosclerotic risk factors . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00225849 |
13,566 | 19,651,589 | : Although findings regarding effects of school-based asthma education programs on quality of life , school absences , and days and nights with symptoms were not consistent , our analyses suggest that school-based asthma education improves knowledge of asthma , self-efficacy , and self-management behaviors | CONTEXT : Asthma self-management education is critical for high- quality asthma care for children .
A number of studies have assessed the effectiveness of providing asthma education in schools to augment education provided by primary care providers .
OBJECTIVE : To conduct a systematic review of the literature on school-based asthma education programs . | This article describes the evaluation of a comprehensive school-based asthma management program in an inner-city , largely African-American school system . All 54 elementary schools ( combined enrollment 13,247 students ) from a single urban school system participated in this study . Schools were r and omly divided between immediate and delayed intervention programs . The intervention consisted of 3 separate educational programs ( for school faculty/staff , students with asthma , and peers without asthma ) and medical management for the children with asthma ( including an Individual Asthma Action Plan , medications , and peakflow meters ) . Children with asthma were identified using a case detection program and 736 were enrolled into the intervention study . No significant differences were observed in school absences , grade point average , emergency room visits , or hospitalizations between the immediate and delayed intervention groups . Significant increases in knowledge were observed in the immediate intervention group . This study of a school-based asthma management education and medical intervention program did not show any differences between the intervention and control groups on morbidity outcomes . Our experience leads us to believe that such measures are difficult to impact and are not always reliable . Future research ers should be aware of the problems associated with using such measures . In addition , connecting children with a regular source of health care in this population was difficult . More intensive methods of medical management , such as school-based health centers or supervised asthma therapy , might prove more effective in inner-city schools The present study investigated schools as an appropriate context for an intervention design ed to produce clinical and psychological benefits for children with asthma . A total of 193 out of 219 ( 88.1 % ) children with asthma ( aged 7–9 yrs ) from 23 out of 24 ( 95.8 % ) schools completed the study . Intervention schools received a staff asthma-training session , advice on asthma policy , an emergency β2-agonist inhaler with spacer and whole-class asthma workshops . Nonintervention schools received no asthma-related input . Intervention children required less general practitioner-prescribed preventer medication despite no differences in symptom control compared with the nonintervention asthmatic group . Increased peer knowledge of asthma may have mediated improved active quality of life in the intervention group , together with increased self-esteem in young females . Those females not receiving the intervention , but identified as being asthmatic within the classroom , and thus possibly stigmatised , reported decreased self-esteem . Lower self-esteem in young males was associated with pet ownership . No change was found in staff knowledge , the establishment of asthma policies or school absences which were low even before intervention . In conclusion , a whole-school intervention can improve the health of children with asthma when followed with support for all children but effects are likely to be modified by sex and the home environment A r and omized trial of an instructional method was conducted in which school nurses taught children asthma self-management principles and skills , including peak flow monitoring , in 20-min , individual sessions over an 8-week period . Thirty-six children participated . An intervention group of 18 children received the teaching sessions . A control group of 18 children received regular care by the nurses , but no teaching sessions . The sample included 64 % boys , 69 % African-Americans , and 69 % Medicaid recipients . The average age of subjects was 10.2 years . The two groups were demographically similar , but despite r and om assignment , the control group had a significantly earlier age of onset of asthma and tended to have had more asthma attacks in the preceding year . These factors were statistically controlled in outcome analyses . Results of group comparisons showed no significant differences in the number of postintervention emergency room visits and days absent from school . However , nurses reported that children who practice d breathing exercises had less anxiety during exacerbations , and the nurses ' knowledge of the children 's baseline peak expiratory flow rates facilitated care of the children . Nurses expressed the opinion that the individual sessions with students might be useful in motivating them to participate effectively in later group sessions . The intervention was well accepted by students , parents , and nurses . We believe that this intervention is promising as a practical , low-cost approach to enhancing children 's asthma self-management skills and warrants further testing in a larger sample , with the intervention conducted over a longer period Pediatric asthma rates are reaching epidemic proportions , adversely affecting children 's quality of life , educational potential , and health care costs , especially those in the inner city . This study evaluated the effectiveness of a school-based asthma case management ( CM ) approach with medically underserved inner-city children attending Memphis City schools . Fourteen elementary schools with high rates of asthma-related hospital utilization were grouped according to school size , percentage of children with asthma enrolled , and percentage of children eligible for free or reduced-price lunch . Schools were r and omized to either a nurse CM intervention or a usual care ( UC ) condition . The CM group included 115 students ; 128 students were in the UC group . A longitudinal design was used to follow students ' progress . Students were primarily African-American children diagnosed with asthma . In CM schools , nurse case managers conducted weekly group sessions incorporating the Open Airways curriculum , followed up on students ' school absences , and coordinated students ' asthma care with families , school personnel , and medical providers . In UC schools , students received routine school nursing services . CM students had fewer school absences than their counterparts in UC schools ( mean 4.38 vs 8.18 days , respectively ) and experienced significantly fewer emergency department visits ( p < .0001 ) and fewer hospital days ( p < .05 ) than UC students . No such differences existed before program initiation . Replication and follow-up in year 2 showed continued significant improvements . School-based nurse CM can achieve significant improvements in school attendance and medical utilization OBJECTIVE To measure the effect of an asthma intervention on the functional status and morbidity of children with undiagnosed asthma . STUDY DESIGN Data from a r and omized trial were used to compare outcomes at baseline and follow-up for children with undiagnosed and diagnosed asthma . We studied 510 symptomatic children with diagnosed asthma ( diagnosed ) and 299 children with symptoms but no diagnosis ( undiagnosed ) . Baseline functioning and morbidity were similar for undiagnosed and diagnosed patients classified as moderate-severe . RESULTS There were fewer undiagnosed reported allergies , seasonal symptoms , and other respiratory diagnoses ( all P < 0.01 ) . Among the moderate-severe , functional status , for example , symptom-days ( P = .02 ) , symptom-nights ( P < .01 ) , and days of restricted activity ( P < .01 ) , was significantly reduced at follow-up for the undiagnosed in the intervention group but not for undiagnosed control subjects . Findings were similar for children with diagnosed asthma . CONCLUSIONS Children with undiagnosed asthma were generally nonatopic , although some had symptoms at a level comparable to children with a diagnosis . The intervention successfully improved functional status for children with undiagnosed asthma as well as for children with diagnosed asthma . These results can be applied to ongoing discussion s related to case detection BACKGROUND Asthma diminishes the health-related quality of life for many school-aged children . This study sought to explore the effect of a School-Based Asthma Education Program ( SBAEP ) on quality of life . METHODS Children with asthma who attended grade s 1 - 5 at two selected schools were requested to participate in this pilot study . Participants at one school were provided with a SBAEP , those at another school ( control group ) were provided with written educational material about asthma . The children completed the Paediatric Asthma Quality of Life Question naire ( PAQLQ ) before and one month after the educational interventions . RESULTS There were clinical ly important improvements in the SBAEP group in quality of life , specifically in the symptom subdomain . CONCLUSIONS The " Air Force " SBAEP appears to result in a favourable trend in quality of life for children . A larger scale trial is required following revisions to the program Abstract Objective : To determine the effect of a peer led programme for asthma education on quality of life and related morbidity in adolescents with asthma . Design : Cluster r and omised controlled trial . Setting : Six high schools in rural Australia . Participants : 272 students with recent wheeze , recruited from a cohort of 1515 students from two school years ( mean age 12.5 and 15.5 years ) ; 251 ( 92.3 % ) completed the study . Intervention : A structured education programme for peers comprising three steps ( the “ Triple A Program ” ) . Main outcome measures : Quality of life , school absenteeism , asthma attacks , and lung function . Results : When adjusted for year and sex , mean total quality of life scores showed significant improvement in the intervention than control group . Clinical ly important improvement in quality of life ( > 0.5 units ) occurred in 25 % of students with asthma in the intervention group compared with 12 % in the control group ( P=0.01 ) . The number needed to treat was 8 ( 95 % confidence interval 4.5 to 35.7 ) . The effect of the intervention was greatest in students in year 10 and in females . Significant improvements occurred in the activities domain ( 41 % v 28 % ) and in the emotions domain ( 39 % v 19 % ) in males in the intervention group . School absenteeism significantly decreased in the intervention group only . Asthma attacks at school increased in the control group only . Conclusion : The triple A programme leads to a clinical ly relevant improvement in quality of life and related morbidity in students with asthma . Wider dissemination of this programme in schools could play an important part in reducing the burden of asthma in Aim : To evaluate the effectiveness of a programme of asthma clubs in improving quality of life in primary school children with asthma . Methods : A cluster r and omised intervention trial was undertaken in 22 primary schools within the urban area of south and east Belfast , Northern Irel and . Schools were r and omised in pairs to immediate or delayed groups . The study subjects comprised 173 children aged 7–11 years whose parents had notified the school of their asthma diagnosis . Children attended school based weekly clubs over an 8 week period . The main outcome measures were the interview administered Paediatric Quality of Life Question naire scores , ranging from 1 ( worst ) to 7 ( best ) , spirometry , and inhaler technique . Results : Over 15 weeks , small but non-significant improvements in the overall quality of life score ( mean 0.20 ; 95 % confidence interval ( CI ) −0.20 to 0.61 ) and in each of its three components , activity limitation ( 0.20 ; −0.43 to 0.84 ) , symptoms ( 0.23 ; −0.23 to 0.70 ) , and emotional function ( 0.17 ; −0.18 to 0.52 ) , were observed in the immediate compared with the delayed group . Inhaler technique at week 16 was markedly better in the immediate group , with 56 % having correct technique compared with 15 % in the delayed group . No significant effect of the intervention on spirometry results could be demonstrated . Conclusion : This primary school based asthma education programme result ed in sustained improvements in inhaler technique , but changes in quality of life scores were not significant OBJECTIVE To evaluate an asthma education program for children with asthma that is delivered in their school by certified asthma educators from a local hospital-based asthma center . STUDY DESIGN R and omized controlled trial . SETTING Twenty-six elementary schools located in a suburb of Toronto . PARTICIPANTS A total of 256 children in grade s 2 to 5 with asthma and their parents were r and omized to control and experimental groups . INTERVENTION Children in the experimental group received the " Roaring Adventures of Puff " asthma education program over the course of six weekly 1-h sessions . Those in the control group continued receiving usual care . MEASUREMENTS AND RESULTS Data collection involved measuring asthma quality of life , self-efficacy for managing asthma , school absenteeism , days of interrupted activity , health services use , and parental loss of time from work . Quality of life and self-efficacy data were collected from the children at baseline and 2 months . Telephone parental interviews conducted over 1 year were used to collect data on the remaining variables . Unpaired t test , analysis of variance , and chi2 test were used to determine whether differences existed between the groups . The results are reported as the mean + /- SD . The experimental group demonstrated higher scores than the control group for self-efficacy ( 3.6 + /- 0.7 vs 3.8 + /- 0.9 , respectively ; p < 0.05 ) and quality of life ( 5.0 + /- 1.4 vs 5.5 + /- 1.4 , respectively ; p < 0.05 ) . At 1 year , the experimental group demonstrated fewer mean urgent health-care visits ( 2.5 + /- 2.5 vs 1.7 + /- 1.9 visits per year , respectively ; p < 0.01 ) , days of missed school ( 4.3 + /- 5.7 vs 3.0 + /- 4.4 days per year , respectively ; p > 0.05 ) , and days of interrupted activity ( 9.1 + /- 10.5 vs 6.2 + /- 7.3 days per year ; p < 0.01 ) related to asthma than the control group . There were no differences between the groups for parental work absenteeism or scheduled asthma visits . CONCLUSION Providing an asthma education program to children in their school can significantly improve quality of life and reduce the burden of childhood asthma Our objective was to determine whether an asthma education program in schools would have 1 ) a direct impact on student knowledge and attitudes to asthma and quality of life of the students with asthma , 2 ) an indirect impact on teacher knowledge and attitudes to asthma and on school policies about asthma , and 3 ) a sustainable program after the re sources to implement the research were withdrawn . Seventeen intervention and 15 control schools participated in a controlled trial . Baseline knowledge and attitudes were measured in year 8 students ( ages 13 - 14 years ) and their teachers together with quality of life in the students with asthma . A three-lesson package about asthma was delivered by teachers as part of the Personal Development/Health/Physical Education ( PD/H/PE ) curriculum . Follow-up question naires were administered to students and staff . Efforts to change school policies were documented . Five years after the intervention , PD/H/PE teachers were contacted to determine whether the program was still operating . Main outcome measures included asthma knowledge , attitudes , and quality of life . Question naires were returned by 4,161/4,475 of the year 8 students at baseline and by 3,443 at follow-up . In intervention schools , compared with control schools , students showed improved asthma knowledge ( P < 0.0001 ) , improvement in tolerance to asthma ( P = 0.02 ) , internal control ( P = 0.03 ) , and less tendency to believe in the role of chance in asthma control ( P = 0.04 ) . Students from intervention but not control schools showed significant improvements in overall quality of life ( P = 0.003 vs. P = 0.82 , respectively ) . Teachers from intervention schools showed significant increases in knowledge compared to control schools ( P < 0.0001 ) . Intervention schools were more likely to seek further health education about asthma ( P < 0.01 ) . Five years after the 35 schools involved in the development of the material s or the trial had been offered the Living With Asthma package , 25 ( 71 % ) were still teaching the program to most or all of their students . Fifty-nine of the 61 ( 97 % ) high schools in the Hunter Region now have the program . Management and distribution of the Living With Asthma program have been taken over by the Asthma Foundation of New South Wales . The package has been up date d and is being offered to all high schools throughout New South Wales as part of the National Asthma-Friendly Schools Project . In conclusion , a teacher-led asthma education program in secondary school had direct and indirect beneficial outcomes and was sustained at a high level for 5 years in most schools in the Hunter Region , despite minimal ongoing maintenance and support from health workers INTRODUCTION Asthma is the most prevalent chronic illness , affecting more than 7 million children younger than 17 years . Asthma has become a leading public health concern because of the dramatic rise in the incidence of this disease during the past 15 years , particularly in minority population s. This study tested a two-part intervention on selected psychosocial and health outcomes of 8- to 13-year-old inner city minority students with asthma . METHOD The intervention consisted of participation in an asthma education program ( Open Airways ) followed by 5 monthly visits with a nurse practitioner . The total sample of 52 children was composed of 28 children in the treatment group who received the intervention and 24 children who served as a control group . RESULTS Students in the treatment group scored significantly higher than the control group over time on measures of asthma knowledge , asthma self-efficacy , general self-care practice s , and asthma self-care practice s. No significant differences were found between the two groups on health outcomes . DISCUSSION A school-based intervention program can improve psychosocial outcomes for inner-city minority children with asthma . Recommendations for future research and clinical practice are discussed STUDY OBJECTIVE This study assessed the impact of a comprehensive school-based asthma program on symptoms , grade s , and school absences in children , and parents ' asthma management practice s. DESIGN R and omized controlled trial . SETTING Fourteen elementary schools in low-income neighborhoods in Detroit , MI . PARTICIPANTS Eight hundred thirty-five children with asthma in grade s 2 through 5 and their parents . INTERVENTION The intervention entailed six components for children , their parents , classmates , and school personnel to encourage and enable disease management . MEASUREMENTS AND RESULTS Parents completed telephone interviews and the schools provided data at baseline and 24 months after intervention . At follow-up , treatment children with persistent disease had significant declines in both daytime ( 14 % fewer , p < 0.0001 ) and nighttime ( 14 % fewer , p < 0.0001 ) symptoms . Among children with both mild intermittent and persistent disease , those in the treatment group had 17 % fewer daytime symptoms ( p < 0.0001 ) but 40 % more nighttime symptoms . Treatment children had higher grade s for science ( p < 0.02 ) but not reading , mathematics , or physical education . No differences in school absences for all causes between groups were noted in school records . However , parents of treatment group children reported fewer absences attributable to asthma in the previous 3 months ( 34 % fewer , p < 0.0001 ) and 12 months ( 8 % fewer , p < 0.05 ) . Parents of treatment children had higher scores ( 2.19 greater , p = 0.02 ) on an asthma management index . The program may have stimulated attention to symptoms at night by parents of children with mild intermittent disease . Overall , the intervention provided significant benefits , particularly for children with persistent asthma The goal of this study was to determine the effectiveness of an asthma educational intervention in improving asthma knowledge , self-efficacy , and quality of life in rural families . Children 6 to 12 years of age ( 62 % male , 56 % white , and 22 % Medicaid ) with persistent asthma ( 61 % ) were recruited from rural elementary schools and r and omized into the control st and ard asthma education ( CON ) group or an interactive educational intervention ( INT ) group geared toward rural families . Parent/caregiver and child asthma knowledge , self-efficacy , and quality of life were assessed at baseline and at 10 months post enrollment . Despite high frequency of symptom reports , only 18 % children reported an emergency department visit in the prior 6 months . Significant improvement in asthma knowledge was noted for INT parents and young INT children at follow-up ( Parent : CON = 16.3 ; INT = 17.5 , p < 0.001 ; Young children : CON = 10.8 , INT = 12.45 , p < 0.001 ) . Child self-efficacy significantly increased in the INT group at follow-up ; however , there was no significant difference in parent self-efficacy or parent and child quality of life at follow-up . Asthma symptom reports were significantly lower for the INT group at follow-up . For young rural children , an interactive asthma education intervention was associated with increased asthma knowledge and self-efficacy , decreased symptom reports , but not increased quality of life BACKGROUND We have previously reported a high prevalence of current asthma-related symptoms affecting predominantly Hispanic , socioeconomically disadvantaged schoolchildren in Southeast San Diego . OBJECTIVE We sought to assess the impact of a school-based education program on asthma outcomes . METHODS In cooperation with the San Diego Unified Schools , we developed and implemented a school-based asthma education program . Based on the National Heart , Lung , and Blood Institute consensus guidelines for asthma , the five-session bilingual , interactive curriculum was conducted in 20-minute segments . Asthma knowledge was tested before and after the education program , and asthma severity was prospect ively assessed at monthly intervals . Outcome parameters were compared in educated and control ( noneducated ) fourth grade students with asthma by using nonparametric techniques . RESULTS After asthma education , students demonstrated improvement with increases in mean scores for : asthma knowledge quiz from 9.9 ( SEM = 0.44 , n = 34 ) to 13.7 ( SEM = 0.30 ) ; peak flowmeter technique from 3.9 ( SEM = 0.33 , n = 32 ) to 6.4 ( SEM = 0.29 ) ; and inhaler technique from 2.3 ( SEM = 0.26 , n = 32 ) to 4.3 ( SEM = 0.26 ) . All changes were highly significant ( p < or = 0.00001 as determined by Wilcoxon matched-pairs signed-rank test ) . Mean score comparisons for asthmatic control students given paired examinations after a time interval matched with the educated students , did not reach statistical significance : quiz score of 11.3 ( SEM = 0.80 , n = 11 ) versus 10.9 ( SEM = 0.68 ) , peak flowmeter technique score of 2.6 ( SEM = 0.50 , n = 18 ) versus 3.1 ( SEM = 0.37 ) , and inhaler technique score of 2.5 ( SEM = 0.37 , n = 18 ) versus 2.2 ( SEM = 0.31 ) . Prospect i ve monthly data were collected on 27 educated and 15 control asthmatic subjects . Severity of asthma was not significantly different between groups at entry to the study . Symptom question naires , vali date d for functional asthma severity , revealed a significant reduction in mean symptom scores at 180 days for the educated ( 2.87 , SEM = 0.447 ) versus the control ( 4.36 , SEM = 0.573 ) groups ( p = 0.0188 as determined by the Mann-Whitney U test ) . CONCLUSION Child-centered asthma education can be successfully conducted in the school setting , result ing in increased asthma knowledge , improved skills for peak flowmeter and inhaler use , and a reduction in the severity of asthma symptoms 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 . RATIONALE Urban African-American youth , aged 15 - 19 years , have asthma fatality rates that are higher than in whites and younger children , yet few programs target this population . Traditionally , urban youth are believed to be difficult to engage in health-related programs , both in terms of connecting and convincing . OBJECTIVES Develop and evaluate a multimedia , web-based asthma management program to specifically target urban high school students . The program uses " tailoring , " in conjunction with theory-based models , to alter behavior through individualized health messages based on the user 's beliefs , attitudes , and personal barriers to change . METHODS High school students reporting asthma symptoms were r and omized to receive the tailored program ( treatment ) or to access generic asthma websites ( control ) . The program was made available on school computers . MEASUREMENTS AND MAIN RESULTS Functional status and medical care use were measured at study initiation and 12 months postbaseline , as were selected management behaviors . The intervention period was 180 days ( calculated from baseline ) . A total of 314 students were r and omized ( 98 % African American , 49 % Medicaid enrollees ; mean age , 15.2 yr ) . At 12 months , treatment students reported fewer symptom-days , symptom-nights , school days missed , restricted-activity days , and hospitalizations for asthma when compared with control students ; adjusted relative risk and 95 % confidence intervals were as follows : 0.5 ( 0.4 - 0.8 ) , p = 0.003 ; 0.4 ( 0.2 - 0.8 ) , p = 0.009 ; 0.3 ( 0.1 - 0.7 ) , p = 0.006 ; 0.5 ( 0.3 - 0.8 ) , p = 0.02 ; and 0.2 ( 0.2 - 0.9 ) , p = 0.01 , respectively . Positive behaviors were more frequently noted among treatment students compared with control students . Cost estimates for program delivery were $ 6.66 per participating treatment group student . CONCLUSIONS A web-based , tailored approach to changing negative asthma management behaviors is economical , feasible , and effective in improving asthma outcomes in a traditionally hard-to-reach population Objectives : This study examined the effectiveness in children in China of an asthma education programme adapted from a model developed in the USA . Methods : Six hundred and thirty-nine children in 21 elementary schools in one agricultural and one industrial area participated in a r and omized , controlled trial . Data were collected at baseline and 1 year subsequently . The self-regulation-based programme addressed topics including preventing and managing symptoms , using medicines , and identifying and controlling triggers . Results : Positive effects on treatment children v. control children were noted in school performance ( 0.21 v. -0.06 , p=0.04 ) , absences ( -0.55 v . -0.32 , p=0.02 ) , and home environment ( 1.78 v. 4.75 , p=0.009 ) . Industrial-area children additionally benefited from fewer hospitalizations ( odds ratio=1.96 , p=0.05 ) and asthma-related concerns of parents ( -0.63 v. -0.34 , p=0.001 ) . Agricultural-area parents showed greater improvement in asthma management ( 0.93 v. 0.26 , p=0.0001 ) , and expressed more negative feelings about asthma ( -0.13 v. -0.58 , p=0.04 ) and asthma concerns ( -0.31 v. -0.63 , p=0.0001 ) . Discussion : The programme provided overall benefits related to school performance , absences , and home environment . In the agricultural area , where fewer re sources were available , benefits were fewer and concerns greater . In the industrial area , where education and income were higher , additional benefits related to healthcare use and parents ' quality of life were realized PURPOSE To examine the impact of a peer-led asthma education program on asthma knowledge , attitudes , and quality of life among adolescents . METHODS A controlled trial was conducted in two girls ' high schools situated in an area of high unemployment and low socioeconomic status , and with a large non-English-speaking community . One school received the intervention and the second school acted as a comparison school . The Triple A ( Adolescent Asthma Action ) program was implemented in the intervention school and involved Year 11 student peer leaders instructing Year 10 students about asthma . The Year 10 students then developed asthma-related health messages into student asthma performances which were presented to the main student body . Outcomes were evaluated by question naire . RESULTS The Triple A program led to a significant improvement in asthma knowledge in both students with asthma and their peers . This effect occurred not only in students conducting the asthma performances ( Year 10 ) , but also in students in the audience ( Year 7 ) . Students held favorable attitudes toward asthma , with high degrees of tolerance and moderate internal locus of control . Asthma-related quality of life was not altered by the intervention . CONCLUSION Peer-led asthma education was well received in the high school setting and led to important improvements in asthma knowledge among students with asthma and their peers OBJECTIVE . Children with asthma spend a large portion of their day in school , and the extent to which public schools are prepared to meet their health needs is an important issue . The objective of this study was to identify asthma policies and practice s in rural and urban school setting s and to compare them with current National Heart , Lung , and Blood Institute recommendations . METHODS . A stratified r and om sample of school nurses who represented each of the 500 active Pennsylvania school districts were surveyed in 2004 concerning nurse staffing patterns , availability of asthma monitoring and treatment-related equipment , emergency preparedness , availability of asthma-related support and case management services , school-specific procedures including identification of children with asthma and accessibility of inhaler medication during school hours , presence and content of written asthma management plans , and perceived obstacles to asthma management in the school setting . Sampling weights were incorporated into the analyses to take the survey design into account . RESULTS . The overall response rate was 76 % , with a total of 757 surveys analyzed . In more than half of secondary schools and three quarters of elementary schools , nurses were present < 40 hours per week . Nearly 1 in 5 schools reported that staff who know what to do for a severe asthma attack were not always available . In 72 % of rural schools , children were allowed to self-carry rescue inhalers , as compared with 47 % of urban schools . Asthma management plans were on file for only 1 quarter of children with asthma , and important information often was omitted . Approximately half of the schools were equipped with peak flow meters and nebulizers , and spacers were available in 1 third of schools . CONCLUSIONS . Improvements are needed to bring schools into compliance with current recommendations , including more consistent availability of knowledgeable staff , improved access to asthma monitoring and treatment-related equipment , more universal use of asthma management plans , and greater access to inhalers while at school , including increasing the proportion of children who are allowed to carry and self-administer inhaler medication ISSUES AND PURPOSE Asthma affects 7.4 % of school-age children , with poor children or members of ethnic minorities disproportionately affected . DESIGN AND METHODS A quasiexperimental , year-long pilot study tested the effectiveness of an intervention that included school-based small-group education for children with home-based education for parents . Pretest and two posttest measures were collected . RESULTS Forty-four families completed the study ( 41 % African American , 36 % European American , 23 % Mexican American ) , with 46 % coming from poor or working-class families . Asthma management in the treatment group was lower than the comparison group at baseline , but improved significantly at 6 months and stabilized at 12 months , a trend that was most pronounced among the poorer children . PRACTICE IMPLICATION S Improvements in asthma management point to the need for ongoing asthma education to address learning needs of the children and families Computer-based education in schools is not novel . However , only a few computer games have been introduced into school-based health education programs . This study describes inclusion of an asthma education space adventure game into fourth- grade classrooms . Using the game improved asthma knowledge in the intervention classes . Children in the active participation classroom gained significantly more asthma knowledge over the observation period compared to the classroom that did not play the computer game . Knowledge gained was retained over a four-week period and the addition of physician-led talks appeared to add little to the knowledge gained . " Air Academy : The Quest for Airtopia " is an easy and successful tool for elementary grade asthma-related health education in schools To evaluate the effectiveness of a comprehensive asthma management education program for 7- to 12-year-old children with asthma , entitled Roaring Adventures of Puff ( RAP ) , 18 elementary schools in Edmonton were r and omized to intervention and control groups . Participating in the program were 76 students with asthma in the intervention schools and 86 in the control schools . Children in the intervention schools had statistically significant improvements in unscheduled doctor visits , missed school days , moderate-to-severe parent rating of severity , severity of shortness of breath , limitations in the kind of play , and correct use of medications . Unscheduled doctor visits and missed school days were the only significant improvements in the control group ; however , improvements were about half that of the intervention group . The results showed that a comprehensive , school-based asthma education program is feasible and improves outcomes |
13,567 | 29,913,273 | Many patients in endoscopic remission from UC have no rectal bleeding .
Normal stool frequency associates with endoscopic remission , but many patients have abnormal stool frequencies despite endoscopic remission . | Background & Aims We aim ed to evaluate the association of the patient‐reported outcomes for rectal bleeding and stool frequency among patients with ulcerative colitis ( UC ) in endoscopic remission . | BACKGROUND & AIMS Interobserver differences in endoscopic assessment s contribute to variations in rates of response to placebo in ulcerative colitis ( UC ) trials . We investigated whether central ized review of images could reduce these variations . METHODS We performed a 10-week , r and omized , double-blind , placebo-controlled study of 281 patients with mildly to moderately active UC , defined by an Ulcerative Colitis Disease Activity Index ( UCDAI ) sigmoidoscopy score ≥2 , that evaluated the efficacy of delayed-release mesalamine ( Asacol 800-mg tablet ) 4.8 g/day . Endoscopic images were review ed by a single expert central reader . The primary outcome was clinical remission ( UCDAI , stool frequency and bleeding scores of 0 , and no fecal urgency ) at week 6 . RESULTS The primary outcome was achieved by 30.0 % of patients treated with mesalamine and 20.6 % of those given placebo , a difference of 9.4 % ( 95 % confidence interval [ CI ] , -0.7 % to 19.4 % ; P = .069 ) . Significant differences in results from secondary analyses indicated the efficacy of mesalamine . Thirty-one percent of participants , all of whom had a UCDAI sigmoidoscopy score ≥2 as read by the site investigator , were considered ineligible by the central reader . After exclusion of these patients , the remission rates were 29.0 % and 13.8 % in the mesalamine and placebo groups , respectively ( difference of 15 % ; 95 % CI , 3.5%-26.0 % ; P = .011 ) . CONCLUSIONS Although mesalamine 4.8 g/day was not statistically different from placebo for induction of remission in patients with mildly to moderately active UC , based on an intent-to-treat analysis , the totality of the data supports a benefit of treatment . Central review of endoscopic images is critical to the conduct of induction studies in UC ; Clinical Trials.gov Number , NCT01059344 Background : Patients with ulcerative colitis ( UC ) who are in clinical remission may still have underlying endoscopic inflammation , which is associated with inferior clinical outcomes . The goal of this study was to determine the prevalence of active endoscopic disease , and factors associated with it , in patients with UC who are in clinical remission . Methods : Prospect i ve observational study in a single center . Patients with UC in clinical remission ( by Simple Clinical Colitis Activity Index ) were enrolled prospect ively at the time of surveillance colonoscopy . Disease phenotype , endoscopic activity ( Mayo subscore ) , and histologic score ( Geboes ) were recorded , and blood was drawn for peripheral blood biomarkers . Results : Overall , 149 patients in clinical remission were prospect ively enrolled in this cohort ; 81 % had been in clinical remission for > 6 months , and 86 % were currently prescribed maintenance medications . At endoscopy , 45 % of patients in clinical remission had any endoscopic inflammation ( Mayo endoscopy subscore > 0 ) , and 13 % had scores > 1 . In a multivariate model , variables independently associated with a Mayo endoscopic score > 1 were remission for < 6 months ( P = 0.001 ) , white blood count ( P = 0.01 ) , and C-reactive protein level ( P = 0.009 ) . A model combining these 3 variables had a sensitivity of 94 % and a specificity of 73 % for predicting moderate-to-severe endoscopic activity in patients in clinical remission ( area under the curve , 0.86 ) . In an unselected subgroup of patients who had peripheral blood mononuclear cell messenger RNA profiling , GATA3 messenger RNA levels were significantly higher in patients with endoscopic activity . Conclusions : Duration of clinical remission , white blood count , and C-reactive protein level can predict the probability of ongoing endoscopic activity , despite clinical remission in patients with UC . These parameters could be used to identify patients who require intensification of treatment to achieve mucosal healing BACKGROUND AND AIMS The aim was to derive health state utility scores in ulcerative colitis ( UC ) by establishing the relationship between the physician-rated ulcerative colitis disease activity index ( UCDAI ) and a patient reported EQ-5D by statistically mapping the two instruments . METHODS In a r and omised controlled trial comparing oral plus enema mesalazine treatment with oral mesalazine treatment alone ( PINCE ) , UCDAI and EQ-5D scores were collected in parallel from patients with active UC . From these data , multinomial logistic regression was used to estimate response probabilities to each of the five domains of the EQ-5D index from assessment of UC disease severity using original and abbreviated ( no endoscopy ) versions of the UCDAI . Predicted EQ-5D responses were converted by Monte Carlo simulation to the EQ-5D index for predicting health-related quality of life ( HRQoL ) . The reliability of the algorithm was tested using UCDAI scores from a second mesalazine RCT ( PODIUM ) . RESULTS The abbreviated-UCDAI showed comparable explanatory performance to the full UCDAI . For patients in remission , mean utility was 0.939 , 0.944 , and 0.940U for PINCE(estimated ) , PINCE(observed ) , and PODIUM , respectively . Mild/moderate and relapsing cases showed mean utilities of 0.801 , 0.811 , and 0.775 , respectively ; whilst for those in severe relapse , the mean utilities were 0.630 , 0.700 and 0.660 units , respectively . The mean squared error between actual and predicted utilities from observations in PINCE was 0.019 . CONCLUSION Response mapping of UC activity to EQ-5D domains produced reliable estimates of patient-rated health state utility consistent with UCDAI rated severity . Comparing abbreviated-UCDAI and full UCDAI suggests that inclusion of endoscopy scores has limited predictive value in estimating patient One hundred forty-two patients with active colonic or ileocolonic Crohn 's disease were included in a multicenter prospect i ve study . Data collection included 28 clinical , biological , and endoscopic items ; the latter were recorded according to a st and ardized colonoscopic protocol ; a previously vali date d endoscopic index of severity was calculated . Oral prednisolone ( 1 mg/kg body wt per day ) was started and maintained until clinical remission and for at least 3 and at most 7 wk . A second clinical biological and endoscopic evaluation was then performed . At initial colonoscopy , mucosal lesions were , by decreasing order of frequency , superficial ulcerations , deep ulcerations , mucosal edema , erythema , pseudopolyps , aphthoid ulcers , ulcerated stenosis , and nonulcerated stenosis ( 93 % , 74 % , 48 % , 44 % , 41 % , 35 % , 10 % , 8 % , and 2 % of cases , respectively ) . No correlation was found between the clinical activity index and any of the endoscopical data ( lesion frequency and surface , endoscopic severity index ) . Ninety-two percent of patients underwent clinical remission within 7 wk of treatment . None of the 28 clinical biological and endoscopical items collected just before treatment could predict clinical response to steroids . Only 38 of the 131 patients in clinical remission were also in endoscopic remission . In conclusion , ( a ) the description and severity of colonoscopic lesions in active Crohn 's disease have been quantified ; ( b ) no correlation exists between clinical severity and nature , surface , or severity of endoscopic lesions ; ( c ) Oral prednisolone ( 1 mg/kg body wt per day ) induces a clinical remission in 92 % of patients within 7 wk ; ( d ) resistance to steroids can not be predicted from the data collected before treatment onset ; and ( e ) only 29 % of patients in clinical remission also achieve endoscopic remission A r and omized clinical trial was conducted to determine whether colonoscopy is useful in deciding how long to maintain steroid treatment in attacks of Crohn 's disease involving the colon . One hundred forty-seven patients with acute attacks of colonic or ileocolonic Crohn 's disease were treated by oral prednisolone , 1 mg.kg-1.day-1 ; 136 achieved clinical remission , but 96 of them still had active endoscopic lesions and were r and omized either to immediate start of steroid tapering ( group A ; n = 46 ) or to continued prednisolone treatment at the same dosage for 5 more weeks before steroid tapering was begun ( group B ; n = 50 ) . In the remaining 40 patients ( already in endoscopic remission , group C ) , steroid tapering was begun immediately . After prednisolone discontinuation , patients were followed up for 18 months or until clinical relapse . Prolongation of prednisolone therapy significantly improved the endoscopic scores in group B ( 30 % of endoscopic remission ) . The frequency of successful steroid weaning was almost identical in groups A and B ( 82 % and 80 % , respectively ) , as was the actuarially calculated relapse clinical rate after steroid withdrawal ( P = 0.22 ) . No factor predictive of clinical relapse could be found . The clinical course of patients in group C was similar to that of those in groups A and B. Overall , only 22 % of the 147 patients were still in clinical remission and off steroids 18 months after prednisolone discontinuation , outlining the need for maintenance therapy . In conclusion , for patients who have achieved clinical remission , adjustment of steroid treatment duration on the basis of endoscopy results is of no benefit , and the endoscopic aspect has no prognostic value ; thus , it appears unnecessary to repeat colonoscopy in such patients before steroid tapering is begun BACKGROUND Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis . METHODS We conducted two integrated r and omized , double-blind , placebo-controlled trials of vedolizumab in patients with active disease . In the trial of induction therapy , 374 patients ( cohort 1 ) received vedolizumab ( at a dose of 300 mg ) or placebo intravenously at weeks 0 and 2 , and 521 patients ( cohort 2 ) received open-label vedolizumab at weeks 0 and 2 , with disease evaluation at week 6 . In the trial of maintenance therapy , patients in either cohort who had a response to vedolizumab at week 6 were r and omly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks . A response was defined as a reduction in the Mayo Clinic score ( range , 0 to 12 , with higher scores indicating more active disease ) of at least 3 points and a decrease of at least 30 % from baseline , with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1 . RESULTS Response rates at week 6 were 47.1 % and 25.5 % among patients in the vedolizumab group and placebo group , respectively ( difference with adjustment for stratification factors , 21.7 percentage points ; 95 % confidence interval [ CI ] , 11.6 to 31.7 ; P<0.001 ) . At week 52 , 41.8 % of patients who continued to receive vedolizumab every 8 weeks and 44.8 % of patients who continued to receive vedolizumab every 4 weeks were in clinical remission ( Mayo Clinic score ≤2 and no subscore > 1 ) , as compared with 15.9 % of patients who switched to placebo ( adjusted difference , 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [ 95 % CI , 14.9 to 37.2 ; P<0.001 ] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [ 95 % CI , 17.9 to 40.4 ; P<0.001 ] ) . The frequency of adverse events was similar in the vedolizumab and placebo groups . CONCLUSIONS Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis . ( Funded by Millennium Pharmaceuticals ; GEMINI 1 Clinical Trials.gov number , NCT00783718 . ) BACKGROUND & AIMS Endoscopy limited to the rectosigmoid colon is the st and ard technique used to measure endoscopic healing in ulcerative colitis ( UC ) clinical trials . We evaluated whether rectosigmoidoscopy adequately measures UC activity in the more proximal colon . METHODS We analyzed data from a phase 2 , placebo-controlled study that evaluated the efficacy and safety of etrolizumab in patients with moderate to severely active UC who had not responded to st and ard therapy . Central readers determined Mayo Clinic endoscopic subscores ( MCSe ) and ulcerative colitis endoscopic index of severity ( UCEIS ) scores from the rectosigmoid and proximal colon in videos of 331 examinations performed at baseline , week 6 , and week 10 . Rates of endoscopic healing ( MCSe ≤ 1 , MCSe = 0 ) and scores from rectosigmoidoscopy and colonoscopy analyses were compared among 239 examinations with endoscopic assessment proximal to the rectosigmoid colon . RESULTS There was a high degree of correlation between findings from rectosigmoidoscopy vs colonoscopy in assessment of disease activity based on MCSe of 2 or higher ( r = 0.84 ) or MCSe of 1 or higher ( r = 0.96 ) , or the UCEIS score ( r = 0.92 ) . In 230 of 239 videos , findings from rectosigmoidoscopy agreed with those from colonoscopy in the detection of active disease ( MCSe ≥ 2 ; n = 205 ) or healing ( MCSe ≤ 1 ; n = 25 ) . In 9 videos ( 2 taken at baseline , 7 taken after treatment ) , colonoscopy found proximal disease activity not detected by rectosigmoidoscopy . Post-treatment discordance was more frequent in the placebo group , affecting assessment of efficacy at week 10 . When endoscopic healing was defined as MCSe of 0 , there were discordant findings from only 1 video . CONCLUSIONS There is a high degree of correlation in assessment s of UC activity made by rectosigmoidoscopy vs colonoscopy . For detection of endoscopic healing ( MCSe ≤ 1 ) , colonoscopy found persistent proximal lesions in the placebo group , which affected efficacy analyses . When endoscopic healing was defined as MCSe of 0 , the concordance between rectosigmoidoscopy and colonoscopy was nearly perfect |
13,568 | 30,016,629 | It was found that multipotent cell transplantation was able to alleviate liver damage and improve liver function .
Multipotent cell transplantation can also enhance the short‐term and medium‐term survival rates of ACLF .
In conclusions , this study suggested that multipotent cell transplantation could be recommended as a potential therapeutic supplementary tool in clinical practice . | & NA ; Acute‐on‐chronic liver failure ( ACLF ) is a serious life‐threatening disease with high prevalence .
Liver transplantation is the only efficient clinical treatment for ACLF .
Because of the rapid progression and lack of liver donors , it is urgent to find an effective and safe therapeutic approach to ACLF .
Recent studies showed that multipotent cell transplantation could improve the patients ’ liver function and enhance their preoperative condition .
Cells such as mesenchymal stem cells , bone marrow mononuclear cells and autologous peripheral blood stem cells , which addressed in this study have all been used in multipotent cell transplantation for liver diseases .
However , its clinical efficiency is still debatable .
This systematic review and meta‐ analysis explored the clinical efficiency of multipotent cell transplantation as a therapeutic approach for patients with ACLF . | AIM To determine the long-term efficacy of autologous bone marrow mononuclear cells ( BM-MNCs ) transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis . METHODS A total of 47 in patients with decompensated liver cirrhosis were enrolled in this trial , including 32 patients undergoing a single BM-MNCs transplantation plus routine medical treatment , and 15 patients receiving medical treatment only as controls . Forty-three of 47 patients were infected with hepatitis B virus . Bone marrow of 80 - 100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery . The efficacy of BM-MNCs transplantation was monitored during a 24-mo follow-up period . RESULTS Liver function parameters in the two groups were observed at 1 mo after BM-MNCs transfusion . Prealbumin level was 118.3 ± 25.3 mg/L vs 101.4 ± 28.7 mg/L ( P = 0.047 ) ; albumin level was 33.5 ± 3.6 g/L vs 30.3 ± 2.2 g/L ( P = 0.002 ) ; total bilirubin 36.9 ± 9.7 mmol/L vs 45.6 ± 19.9 mmol/L ( P = 0.048 ) ; prothrombin time 14.4 ± 2.3 s vs 15.9 ± 2.8 s ( P = 0.046 ) ; prothrombin activity 84.3 % ± 14.3 % vs 74.4 % ± 17.8 % ( P = 0.046 ) ; fibrinogen 2.28 ± 0.53 g/L vs 1.89 ± 0.44 g/L ( P = 0.017 ) ; and platelet count 74.5 ± 15.7 × 10(9)/L vs 63.3 ± 15.7 × 10(9)/L ( P = 0.027 ) in the treatment group and control group , respectively . Differences were statistically significant . The efficacy of BM-MNCs transplantation lasted 3 - 12 mo as compared with the control group . Serious complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also significantly reduced in BM-MNCs transfused patients compared with the controls . However , these improvements disappeared 24 mo after transplantation . CONCLUSION BM-MNCs transplantation is safe and effective in patients with decompensated cirrhosis . It also decreases the incidence of serious complications Background & AimS earch for an effective therapy for patients with hepatitis B virus related acute-on-chronic liver failure ( HBV-ACLF ) remains an important issue . This study investigated the efficacy of umbilical cord-derived mesenchymal stem cell ( UC-MSC ) transplantation in patients with HBV-ACLF . Methods 45 consecutive entecavir-treated HBV-ACLF patients were prospect ively studied . Among these patients , 11 received both plasma exchange ( PE ) and a single transplantation of UC-MSCs ( group A ) , while 34 received only PE ( group B ) . The primary endpoint was survival at 24 months . Results Compared with group B , levels of albumin , alanine aminotransferase , aspartate aminotransferase , total bilirubin , direct bilirubin , prothrombin time ( PT ) , international normalized ratio ( INR ) and model for end-stage liver disease score in group A improved significantly at 4 weeks after transplantation ( p < 0.05 ) . Levels of albumin , PT and INR in group A were also markedly improved at 24 months ( p < 0.05 ) . Group A had significantly higher cumulative survival rate at 24 months ( 54.5 % v.s. 26.5 % , p = 0.015 by log rank test ) . Between the two groups , levels of creatinine , White blood cell , hemoglobin and platelet were similar . HBeAg loss and hepatocellular carcinoma incidence were similar at 24 months . Group assignment ( relative risk : 2.926 , 95%confidence interval : 1.043–8.203 , p = 0.041 ) was an independent predictor for survival at 24 months . Success rate of UC-MSC transplantation was 100 % in group A. No severe adverse event was observed in any patient . Conclusion UC-MSC transplantation is safe and effective for HBV-ACLF patients treated with PE and entecavir . It further improves the hepatic function and survival UNLABELLED Acute-on-chronic liver failure ( ACLF ) is characterized by acute decompensation ( AD ) of cirrhosis , organ failure(s ) , and high 28-day mortality . We investigated whether assessment s of patients at specific time points predicted their need for liver transplantation ( LT ) or the potential futility of their care . We assessed clinical courses of 388 patients who had ACLF at enrollment , from February through September 2011 , or during early ( 28-day ) follow-up of the prospect i ve multicenter European Chronic Liver Failure ( CLIF ) ACLF in Cirrhosis study . We assessed ACLF grade s at different time points to define disease resolution , improvement , worsening , or steady or fluctuating course . ACLF resolved or improved in 49.2 % , had a steady or fluctuating course in 30.4 % , and worsened in 20.4 % . The 28-day transplant-free mortality was low-to-moderate ( 6%-18 % ) in patients with nonsevere early course ( final no ACLF or ACLF-1 ) and high-to-very high ( 42%-92 % ) in those with severe early course ( final ACLF-2 or -3 ) independently of initial grade s. Independent predictors of course severity were CLIF Consortium ACLF score ( CLIF-C ACLFs ) and presence of liver failure ( total bilirubin ≥12 mg/dL ) at ACLF diagnosis . Eighty-one percent had their final ACLF grade at 1 week , result ing in accurate prediction of short- ( 28-day ) and mid-term ( 90-day ) mortality by ACLF grade at 3 - 7 days . Among patients that underwent early LT , 75 % survived for at least 1 year . Among patients with ≥4 organ failures , or CLIF-C ACLFs > 64 at days 3 - 7 days , and did not undergo LT , mortality was 100 % by 28 days . CONCLUSIONS Assessment of ACLF patients at 3 - 7 days of the syndrome provides a tool to define the emergency of LT and a rational basis for intensive care discontinuation owing to futility Human mesenchymal stem/stromal cells ( MSCs ) have been explored in a number of clinical trials as a possible method of treating various diseases . However , the effect of long-term cell expansion in vitro on physiological function and genetic stability is still poorly understood . In this study , MSC cultures derived from bone marrow and liver were evaluated for the presence of aberrant cells following long-term expansion . In 46 independent cultures , four batches of transformed MSCs ( TMCs ) were found , which were all beyond the culture period of five weeks . These aberrant cells were first identified based on the appearance of abnormal cytology and the acquirement of growth advantage . Despite common MSC markers being diminished or absent , TMCs remain highly susceptible to lysis by allogenic natural killer ( NK ) cells . When transplanted into immunodeficient mice , TMCs formed sarcoma-like tumors , whereas parental MSCs did not form tumors in mice . Using a combination of high-resolution genome-wide DNA array and short-t and em repeat profiling , we confirmed the origin of TMCs and excluded the possibility of human cell line contamination . Additional genomic duplication and deletions were observed in TMCs , which may be associated with the transformation event . Using gene and microRNA expression arrays , a number of genes were identified that were differentially expressed between TMCs and their normal parental counterparts , which may potentially serve as biomarkers to screen cultures for evidence of early transformation events . In conclusion , the spontaneous transformation of MSCs result ing in tumorigenesis is rare and occurs after relatively long-term ( beyond five weeks ) culture . However , as an added safety measure , cultures of MSCs can potentially be screened based on a novel gene expression signature Background : Chronic hepatitis B virus ( HBV ) infection may eventually lead to decompensated liver cirrhosis , which is a terminal illness . Objectives : The aim of this study was to investigate the therapeutic efficacy of autologous peripheral blood stem cell ( APBSC ) transplantation to improve portal vein hemodynamics in patients with HBV-related decompensated cirrhosis . Patients and Methods : This prospect i ve study included 68 hospitalized patients who were diagnosed with HBV-related decompensated cirrhosis . These patients were divided into two groups : the transplantation group included 33 patients , while the control group included 35 . Both groups received conventional medical treatment simultaneously , and APBSC transplantation was performed on the patients in the transplantation group . We evaluated the effects of APBSC transplantation on postoperative liver function using the following indices : total bilirubin , serum prothrombin and albumin , spleen size , and portal vein hemodynamics . Postoperatively , all of the patients were followed up at 24 , 36 , and 48 weeks . Results : The transplantation group had no serious reactions . Compared with the control group , albumin and prothrombin activity in the transplantation group was significantly improved at 24 , 36 , and 48 weeks after the procedure , and spleen length and portal vein diameter were substantially reduced at 48 weeks . The velocity of peak portal vein blood flow and mean maximum portal vein blood flow were greatly increased in the APBSC transplantation group at 36 and 48 weeks , respectively ; however , there was also decreased portal vein diameter , which reduced portal vein pressure in patients with HBV-related decompensated cirrhosis . Conclusions : APBSC transplantation greatly benefits HBV-linked decompensated cirrhosis patients and should be recommended in clinical practice Objectives Counseling patients with acute-on-chronic hepatitis B liver failure ( ACHBLF ) on their individual risk of short-term mortality is challenging . This study aim ed to develop a conditional survival estimate ( CSE ) for predicting individualized mortality risk in ACHBLF patients . Methods We performed a large prospect i ve cohort study of 278 ACHBLF patients from December 2010 to December 2013 at three participating medical centers . The Kaplan-Meier method was used to calculate the cumulative overall survival ( OS ) . Cox proportional hazard regression models were used to analyze the risk factors associated with OS . 4-week CSE at “ X ” week after diagnostic established were calculated as CS4 = OS(X+4)/OS(X ) . Results The actual OS at 2 , 4 , 6 , 8 , 12 weeks were 80.5 % , 71.8 % , 69.3 % , 66.0 % and 63.7 % , respectively . Using CSE , the probability of surviving an additional 4 weeks , given that the patient had survived for 1 , 3 , 5 , 7 , 9 weeks was 74 % , 86 % , 92 % , 93 % , 97 % , respectively . Patients with worse prognostic feathers , including MELD > 25 , Child grade C , age > 45 , HE , INR > 2.5 , demonstrated the greatest increase in CSE over time , when compared with the “ favorable ” one ( Δ36 % vs. Δ10 % ; Δ28 % vs. Δ16 % ; Δ29 % vs. Δ15 % ; Δ60 % vs. Δ12 % ; Δ33 % vs. Δ12 % ; all P < 0.001 ; respectively ) . Conclusions This easy-to-use CSE can accurately predict the changing probability of survival over time . It may facilitate risk communication between patients and physicians Human umbilical cord mesenchymal stem cells ( HUMSCs ) are highly proliferative and can be induced to differentiate into advanced derivatives of all three germ layers . Thus , HUMSCs are considered to be a promising source for cell-targeted therapies and tissue engineering . However there are reports on spontaneous transformation of mesenchymal stem cells ( MSCs ) derived from human bone marrows . The capacity for HUMSCs to undergo malignant transform spontaneously or via induction by chemical carcinogens is presently unknown . Therefore , we isolated HUMSCs from 10 donors and assessed their transformation potential either spontaneously or by treating them with 3-methycholanthrene ( 3-MCA ) , a DNA-damaging carcinogen . The malignant transformation of HUMSCs in vitro was evaluated by morphological changes , proliferation rates , ability to enter cell senescence , the telomerase activity , chromosomal abnormality , and the ability to form tumors in vivo . Our studies showed that HUMSCs from all 10 donors ultimately entered senescence and did not undergo spontaneous malignant transformation . However , HUMSCs from two of the 10 donors treated with 3-MCA displayed an increased proliferation rate , failed to enter senescence , and exhibited an altered cell morphology . When these cells ( tHUMSCs ) were injected into immunodeficient mice , they gave rise to sarcoma-like or poorly differentiated tumors . Moreover , in contrast to HUMSCs , tHUMSCs showed a positive expression of human telomerase reverse transcriptase ( hTERT ) and did not exhibit a shortening of the relative telomere length during the long-term culture in vitro . Our studies demonstrate that HUMSCs are not susceptible to spontaneous malignant transformation . However , the malignant transformation could be induced by chemical carcinogen 3-MCA Objective Impaired liver regeneration is associated with a poor outcome in patients with decompensated alcoholic liver disease ( ALD ) . We assessed whether autologous bone marrow mononuclear cell transplantation ( BMMCT ) improved liver function in decompensated ALD . Design 58 patients ( mean age 54 yrs ; mean MELD score 19 , all with cirrhosis , 81 % with alcoholic steatohepatitis at baseline liver biopsy ) were r and omized early after hospital admission to st and ard medical therapy ( SMT ) alone ( n = 30 ) , including steroids in patients with a Maddrey ’s score ≥32 , or combined with G-CSF injections and autologous BMMCT into the hepatic artery ( n = 28 ) . Bone marrow cells were harvested , isolated and reinfused the same day . The primary endpoint was a ≥3 points decrease in the MELD score at 3 months , corresponding to a clinical ly relevant improvement in liver function . Liver biopsy was repeated at week 4 to assess changes in Ki67+/CK7 + hepatic progenitor cells ( HPC ) compartment . Results Both study groups were comparable at baseline . After 3 months , 2 and 4 patients died in the BMMCT and SMT groups , respectively . Adverse events were equally distributed between groups . Moderate alcohol relapse occurred in 31 % of patients . The MELD score improved in parallel in both groups during follow-up with 18 patients ( 64 % ) from the BMMCT group and 18 patients ( 53 % ) from the SMT group reaching the primary endpoint ( p = 0.43 ( OR 1.6 , CI 0.49–5.4 ) in an intention to treat analysis . Comparing liver biopsy at 4 weeks to baseline , steatosis improved ( p<0.001 ) , and proliferating HPC tended to decrease in both groups ( −35 and −33 % , respectively ) . Conclusion Autologous BMMCT , compared to SMT is a safe procedure but did not result in an exp and ed HPC compartment or improved liver function . These data suggest either insufficient regenerative stimulation after BMMCT or resistance to liver regenerative drive in patients with decompensated alcoholic cirrhosis . Trial Registration Controlled-Trials.com IS RCT N83972743 Mortality from hepatitis B virus (HBV)-related acute-on-chronic liver failure ( ACLF ) is high due to limited treatment options . Pre clinical and clinical investigations have proved that treatment with mesenchymal stromal cells ( MSCs ) is beneficial for recovery from liver injury . We hypothesized that the outcome of HBV-related ACLF would be improved by MSC treatment . From 2010 to 2013 , 110 patients with HBV-related ACLF were enrolled in this open-label , nonblinded r and omized controlled study . The control group ( n = 54 ) was treated with st and ard medical therapy ( SMT ) only . The experimental group ( n = 56 ) was infused weekly for 4 weeks with 1.0 to 10 × 105 cells/kg allogeneic bone marrow-derived MSCs and then followed for 24 weeks . The cumulated survival rate of the MSC group was 73.2 % ( 95 % confidence interval 61.6%-84.8 % ) versus 55.6 % ( 95 % confidence interval 42.3%-68.9 % ) for the SMT group ( P = 0.03 ) . There were no infusion-related side effects , but fever was more frequent in MSC compared to SMT patients during weeks 5 - 24 of follow-up . No carcinoma occurred in any trial patient in either group . Compared with the control group , allogeneic bone marrow-derived MSC treatment markedly improved clinical laboratory measurements , including serum total bilirubin and Model for End-Stage Liver Disease scores . The incidence of severe infection in the MSC group was much lower than that in the SMT group ( 16.1 % versus 33.3 % , P = 0.04 ) . Mortality from multiple organ failure and severe infection was higher in the SMT group than in the MSC group ( 37.0 % versus 17.9 % , P = 0.02 ) . CONCLUSION Peripheral infusion of allogeneic bone marrow-derived MSCs is safe and convenient for patients with HBV-related ACLF and significantly increases the 24-week survival rate by improving liver function and decreasing the incidence of severe infections . ( Hepatology 2017;66:209 - 219 ) UNLABELLED The present study assessed the effects of intraportal infusions of autologous bone marrow-derived mononuclear cells ( MNCs ) and /or CD133 + cells on liver function in patients with decompensated cirrhosis . We r and omly assigned 27 eligible patients to a placebo , MNCs , and /or CD133 + cells . Cell infusions were performed at baseline and month 3 . We considered the absolute changes in the Model for End-Stage Liver Disease ( MELD ) scores at months 3 and 6 after infusion as the primary outcome . The participants and those who assessed the outcomes were unaware of the treatment intervention assignments . After 6 months , 9 patients were excluded because of liver transplantation ( n=3 ) , hepatocellular carcinoma ( n=1 ) , loss to follow-up ( n=3 ) , and death ( n=2 ) . The final analysis included 4 patients from the CD133 + group , 8 from the MNC group , and 6 from the placebo group . No improvement was seen in the MELD score at month 6 using either CD133 + cells or MNC infusions compared with placebo . However , at month 3 after infusion , a trend was seen toward a higher mean absolute change in the MELD score in patients who had received CD133 + cells compared with placebo ( -2.00±1.87 vs. -0.13±1.46 ; p=.08 ) . No significant adverse events occurred in the present study . A transient improvement in the MELD score was observed in subjects treated with CD133 + cells but not in the MNC or placebo group . Although the study was not powered to make definitive conclusions , the data justify further study of CD133 + therapy in cirrhotic patients . SIGNIFICANCE Cell therapy is a new approach in liver disease . Several clinical experiments have been reported on the safety of bone marrow-derived stem cells to treat liver disorders . However , the effectiveness of these approaches in the long-term follow-ups of patients initiated controversial discussion s among the scientific community . A double-blind r and omized controlled trial was design ed to address this concern scientifically . A transient improvement in the patients ' signs occurred ; however , for a sustainable result , more work is needed . The results of multiple administrations of cells reported in the present study can be compared with the results from other single-injection studies BACKGROUND & AIMS There has been great interest in recent years to take advantage of bone marrow stem cells to treat cirrhosis . Our uncontrolled trial showed promising results for bone marrow mesenchymal stem cell ( MSC ) transplantation in cirrhosis . Therefore , we conducted a r and omized , placebo-controlled trial to evaluate the efficacy of autologous MSC transplantation in cirrhosis . METHODS The enrolled patients with decompensated cirrhosis were r and omly assigned to receive MSC or placebo infusions . A median of 195 million ( range : 120 - 295 million ) cultured MSCs were infused through a peripheral vein . The primary outcome was absolute changes in MELD score . Secondary outcomes were absolute changes in Child score , liver function tests and liver volumes between the MSC and placebo group 12 months after infusion . RESULTS A total of 27 patients were enrolled . Of these , 15 patients received MSC and 12 patients received placebo . One patient in the MSC group and one patient in the placebo group were lost to follow-up . Three patients in the MSC group died of liver failure 3 months ( one patient ) , or 5 months ( two patients ) after cellular infusion . The baseline MELD scores of the deceased patients were significantly higher than those who remained alive in either group ( 20.0 vs. 15.1 ; P = 0.02 ) . The absolute changes in Child scores , MELD scores , serum albumin , INR , serum transaminases and liver volumes did not differ significantly between the MSC and placebo groups at 12 months of follow-up . CONCLUSION Based on this r and omized controlled trial , autologous bone marrow MSC transplantation through peripheral vein probably has no beneficial effect in cirrhotic patients . Further studies with higher number of patients are warranted to better clarify the impact of MSC infusion through peripheral vein or portal vein in cirrhosis Decompensated liver cirrhosis ( LC ) , a life-threatening complication of chronic liver disease , is one of the major indications for liver transplantation . Recently , mesenchymal stem cell ( MSC ) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans . This study examined the safety and efficacy of umbilical cord-derived MSC ( UC-MSC ) in patients with decompensated LC . A total of 45 chronic hepatitis B patients with decompensated LC , including 30 patients receiving UC-MSC transfusion , and 15 patients receiving saline as the control , were recruited ; clinical parameters were detected during a 1-year follow-up period . No significant side-effects and complications were observed in either group . There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls ( P < 0.05 ) . UC-MSC therapy also significantly improved liver function , as indicated by the increase of serum albumin levels , decrease in total serum bilirubin levels , and decrease in the sodium model for end-stage liver disease scores . UC-MSC transfusion is clinical ly safe and could improve liver function and reduce ascites in patients with decompensated LC . UC-MSC transfusion , therefore , might present a novel therapeutic approach for patients with decompensated LC Objective It is difficult to predict the outcome in patients with acute liver failure ( ALF ) using existing prognostic models . This study investigated whether early changes in the levels of dynamic variables can predict outcome better than models based on static baseline variables . Design 380 patients with ALF ( derivation cohort n=244 , validation cohort n=136 ) participated in a prospect i ve observational study . The derivation cohort was used to identify predictors of mortality . The ALF early dynamic ( ALFED ) model was constructed based on whether the levels of predictive variables remained persistently high or increased over 3 days above the discriminatory cut-off values identified in this study . The model had four variables : arterial ammonia , serum bilirubin , international normalised ratio and hepatic encephalopathy > grade II . The model was vali date d in a cohort of 136 patients with ALF . Results The ALFED model demonstrated excellent discrimination with an area under the receiver operator characteristic curve of 0.91 in the derivation cohort and of 0.92 in the validation cohort . The model was well calibrated in both cohorts and showed a similar increase in mortality with increasing risk scores from 0 to 6 . The performance of the ALFED model was superior to the King 's College Hospital criteria and the Model for End stage Liver Disease score , even when their 3-day serial values were taken into consideration . An ALFED score of ≥4 had a high positive predictive value ( 85 % ) and negative predictive value ( 87 % ) in the validation cohort . Conclusion The ALFED model accurately predicted outcome in patients with ALF , which may be useful in clinical decision-making Acute-on-chronic liver failure ( ACLF ) is a severe , life-threatening complication , and new and efficient therapeutic strategies for liver failure are urgently needed . Mesenchymal stem cell ( MSC ) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases . We assessed the safety and initial efficacy of umbilical cord-derived MSC ( UC-MSC ) transfusions for ACLF patients associated with hepatitis B virus ( HBV ) infection . A total of 43 ACLF patients were enrolled for this open-labeled and controlled study ; 24 patients were treated with UC-MSCs , and 19 patients were treated with saline as controls . UC-MSC therapy was given three times at 4-week intervals . The liver function , adverse events , and survival rates were evaluated during the 48-week or 72-week follow-up period . No significant side effects were observed during the trial . The UC-MSC transfusions significantly increased the survival rates in ACLF patients ; reduced the model for end-stage liver disease scores ; increased serum albumin , cholinesterase , and prothrombin activity ; and increased platelet counts . Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions . UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients |
13,569 | 31,571,246 | There was inconsistent evidence for a link between following a vegetarian diet and dental caries or the number of natural teeth .
Conclusions Within the limitations of the present study , the findings suggest that following a vegetarian diet may be associated with a greater risk of dental erosion | Abstract Objectives People following a vegetarian diet could be more prone to oral health problems than people following a nonvegetarian diet .
The aim of this systematic review was to examine the possible impacts of following a vegetarian diet on dental hard tissues , focusing on caries development , dental erosion and number of natural teeth . | Background / Objectives : Caries and erosion are common diseases of the dental hard tissues . The influence of vegetarianism on the development of caries and erosion has scarcely been investigated in the past . The aim of the present study was to evaluate the influence of fruit consumption and topical fluoride application on the prevalence of caries and erosion in vegetarians . Subjects/ Methods : In 100 vegetarians and 100 nonvegetarians , a dental examination was performed . The indices for decayed , missing , filled teeth ( DMFT ) and surfaces ( DMFS ) were determined . DMFT and DMFS were subdivided into decayed teeth ( DT ) , filled teeth ( FT ) , decayed surfaces ( DS ) and filled surfaces ( FS ) . In addition , the hygiene index and the number of teeth with dental erosion ( DE ) , root caries ( RC ) and overhanging restoration margins ( ORM ) were recorded . A question naire assessed patients ’ eating habits , frequency of oral hygiene , dentist visits and topical fluoride application . For statistical analysis , unpaired t-test , Mann – Whitney test and Pearson ’s chi-square test were applied . Results : Vegetarians had significantly more DT ( P<0.001 ) , DS ( P<0.001 ) , more teeth with DE ( P=0.026 ) , RC ( P=0.002 ) and ORM ( P<0.001 ) than nonvegetarians . Daily consumption of fruits was significantly more prevalent ( P<0.001 ) , and topical fluoride application was less prevalent ( P<0.001 ) in vegetarians compared with nonvegetarians . In particular , fluoride-containing toothpaste ( P<0.001 ) and table salt ( P=0.039 ) were less frequently used in vegetarians . Conclusion : The presented data suggest that vegetarians have an increased risk for caries and erosion . Topical fluoride application was shown to be effective in preventing caries , but not in preventing erosion AIM The aim of this paper was to investigate the effects of fluorotherapy on the oral health of subjects who had been following a vegan diet ( lacking in meat and animal derivatives ) for a long period of time ( at least 1 year and 6 months ) . METHODS A preliminary study ( t0 ) evaluated 50 subjects , all from northern Italy and aged 24 - 60 years ( 28 male and 22 female ) who had been following a vegan diet for a minimum of 18 months to a maximum of 20 years , and compared them with a control group of 50 individuals following a Mediterranean diet . All vegan subjects showed oral changes such as white spots , lesions invisible to the naked eye and decreased salivary pH values ( ~5 - 6 ) . In a second study ( t1 ) , the 50 vegan subjects were r and omly divided into two subgroups of 25 . Subgroup SG1 underwent fluorotherapy with sodium fluoride ( Elmex fluoride gel ® 1.25 % ) administered once daily for 1 year . Subgroup SG2 served as controls and did not receive fluorotherapy . The following parameters were recorded before the start of fluorotherapy and again after 1 year : salivary pH ; Decayed , Missing , Filled teeth Index ; presence and location of white spots and lesions not visible to the naked eye ; Plaque Index , and Gingival Index . RESULTS In SG1 , larger lesions became smaller in diameter and small lesions disappeared , a statistically significant improvement compared with SG2 , despite the persistence of restricted eating habits and the oral hygiene conditions being similar to those at t0 . Salivary pH showed no significant change in either subgroup . CONCLUSION Daily application of a topical 1.25 % fluoride gel is effective in reducing the incidence of white spot lesions caused by a vegan diet |
13,570 | 21,249,669 | When used alone , misoprostol was an effective inductive agent , though it appeared to be more effective in combination with mifepristone .
Misoprostol was preferably administered vaginally , although among multiparous women sublingual administration appeared equally effective .
No r and omised trials comparing doses of misoprostol were identified ; however low doses of misoprostol appear to be associated with fewer side-effects while moderate doses appear to be more efficient in completing abortion .
Indications for surgical evacuation include retained products of the placenta and heavy vaginal bleeding .
Medical abortion in the second trimester using the combination of mifepristone and misoprostol appeared to have the highest efficacy and shortest abortion time interval .
Where mifepristone is not available , misoprostol alone is a reasonable alternative .
Apart from pain , the side-effects of vaginal misoprostol are usually mild and self limiting . | BACKGROUND With the improvement of ultrasound technology , the likelihood of detection of major fetal structural anomalies in mid-pregnancy has increased considerably .
Upon the detection of serious anomalies , women typically are offered the option of pregnancy termination .
Additionally , there are still many reasons other than fetal anomalies why women seek abortion in the mid-trimester .
OBJECTIVES To compare different methods of second trimester medical termination of pregnancy for their efficacy and side-effects . | A prospect i ve r and omized double-blind placebo-controlled trial was conducted in 13 subjects to find out whether mifepristone treatment could facilitate termination of second trimester pregnancy by sulprostone . The women received either 600 mg oral mifepristone or placebo tablets 36 hours before the administration of intramuscular sulprostone 0.5 mg every 6 hours . The median interval between the administration of sulprostone and abortion in the mifepristone group ( 4.6 hours ) was significantly shorter than that in the placebo group ( 20 hours ) . The amount of sulprostone required was also significantly less in the mifepristone group . There was no significant difference in the incidence of side effects or analgesic requirement between the two groups . We conclude that oral mifepristone is useful in facilitating termination of second trimester pregnancies by sulprostone Objective To compare intramuscular ( IM ) prostagl and in 15 methyl-F2α ( 15M-PGE2α ) with prostagl and in E2 ( PGE2 ) vaginal suppositories for second-trimester abortion in terms of efficacy and side effects . Methods Fifty-one women were r and omized to receive either 15M-PGF2α IM injections or PGE2 intravaginal suppositories for second-trimester abortion . Efficacy and side effects of the two agents were analyzed by two-tailed t tests , x2 analysis with Fisher exact test , and survival analysis . Results The mean times to rupture of membranes , delivery of fetus , and delivery of placenta were significantly less for women receiving PGE2 vaginal suppositories . The cumulative abortion rate after 24 hours for the PGE,2 group was 96 % , compared with 69 % for the 15M-PGF2α group . Although there were few differences in side effects , the 15M-PGF2α group had significantly fewer headaches , fevers , and chills . Conclusion Intravaginal PGE2 is superior to IM 15M-PGF2α for second-trimester abortion Objective The aim of this r and omized prospect i ve study was to compare efficacy and side effects of saline moistened misoprostol with dry misoprostol , administered 800 μg intravaginally every 6 h up to a maximum of 3 doses in 24 h for second trimester pregnancy termination . Material s and methods A total of 81 women seeking termination of second trimester pregnancy ( 55 fetal death , 17 fetal structural anomaly , 5 chromosomal abnormality , 4 other reasons ) were r and omly assigned to one of two treatment groups : ( 1 ) intravaginal non-moistened ( dry ) misoprostol in group A ( n = 40 ) or ( 2 ) misoprostol moistened with 3 ml of saline in group B ( n = 41 ) . Results All of the patients in either group aborted within 48 h ( 100 % success rate ) . Delivery was achieved in a median ( interquartile range ) of 13 ( 40 ) h with the group A protocol and 12 ( 36 ) h with the group B protocol ( P = 0.652 ) . Delivery with first dose , delivery within 12 h and delivery within 24 h were similar ( P > 0.05 ) in group B ( 34.1 , 87.5 and 60 % , respectively ) and group A ( 25 , 82.9 , 46.3 , respectively ) . Both treatment regimens were tolerable and with similar side effects . Conclusion Misoprostol moistened with saline was not more effective than dry misoprostol for second trimester pregnancy termination OBJECTIVE To study the effect of mifepristone for priming and induction of second-trimester abortion in conjunction with a high-concentration oxytocin drip . STUDY DESIGN Prospect i ve , r and omized , placebo-controlled , pilot study . Thirty patients with 14 - 25 weeks ' gestational age abortion received either 600 mg of mifepristone or placebo in 3 identical capsules followed , 48 hours later , by a high-concentration oxytocin drip ( HCOD ) . RESULTS The mifepristone group showed significantly higher success rates as compared to the placebo group ( 92.3 % vs. 52.9 % , p<0.05 ) . The time interval to abortion ( from beginning of HCOD ) was also significantly shorter in the mifepristone group as compared to the placebo group ( 11.3 + /- 6.0 hours vs. 17.6 + /- 6.5 hours , p < 0.05 ) . Probability of success as calculated by the Kaplan-Meier method was found to be highly significant ( log rank test p = 0.001 ) . CONCLUSION Our results suggest that mifepristone is very effective for priming and induction of second-trimester abortion and shortens significantly the time interval to evacuation following HCOD BACKGROUND The pharmacokinetic parameters of four different routes of administration of a single dose of 400 microg of misoprostol were studied . METHODS A total of 40 women undergoing termination of pregnancy by suction evacuation was r and omized by computer model to receive 400 microg of misoprostol by one of four routes : ( i ) sublingual ( ii ) oral ( iii ) vaginal and ( iv ) vaginal with addition of water . Venous blood sample s were taken at 0 , 1 , 2 , 5 , 10 , 20 , 30 , 45 , 60 , 120 , 240 and 360 min after the administration of misoprostol . Misoprostol acid ( MPA ) was determined in serum sample s using gas chromatography/t and em mass spectrometry . RESULTS Sublingual misoprostol achieved the highest serum peak concentration ( Cmax ) ( 574.8 + /- 250.7 pg/ml ) of MPA and this was significantly higher than those in the other groups [ Oral : 287.6 + /- 144.3 pg/ml ( P < 0.01 ) , vaginal : 125.2 + /- 53.8 pg/ml ( P < 0.001 ) and vaginal with water : 162.8 + /- 57.1 pg/ml ( P < 0.001 ) ] . The time to peak concentration ( Tmax ) was similar in both the sublingual ( 26.0 + /- 11.5 min ) and oral groups ( 27.5 + /- 14.8 min ) and was significantly shorter than those in both vaginal groups . The area under the MPA concentration versus time curve up to 360 min in the sublingual group ( 743.7 + /- 291.2 pg.h/ml ) was significantly greater than those in oral ( 402.8 + /- 151.6 pg.h/ml , P < 0.05 ) and vaginal ( 433.7 + /- 182.6 pg.h/ml , P < 0.05 ) groups , but no significant difference was found between sublingual and vaginal administration if water ( 649.3 + /- 333.8 pg.h/ml ) was added . CONCLUSION The new sublingual route of administration of misoprostol demonstrated a great potential to be developed into a method of medical abortion It is known that when misoprostol is given at 200 microg every 3 h after mifepristone pretreatment , the vaginal route is more effective than the oral route . However , women prefer the oral route . This r and omized study was to test our hypothesis that oral misoprostol 400 microg is as effective as vaginal misoprostol 200 microg when given every 3 h in termination of second trimester pregnancy after priming with mifepristone . A total of 142 patients was r and omly assigned to group 1 ( 200 mg mifepristone + 400 microg oral misoprostol every 3 h up to five doses ) or group 2 ( 200 mg mifepristone + 200 microg vaginal misoprostol every 3 h up to five doses ) . The incidence of side-effects and the preference study were assessed through a st and ardized question naire during and after the abortion . For the oral group , both the incidence of diarrhoea ( 40.0 versus 23.2 % , P = 0.03 ) and the amount of drug used ( 1734 compared with 812 microg , P < 0.0001 ) were significantly higher than that of the vaginal group but the incidence of fever appeared to be lower ( not significant ) . There was no significant difference in complete abortion rate : 81.4 % in the oral group and 75.4 % in the vaginal group . The median induction-abortion interval was similar in the two groups ( 10.4 versus 10.0 h ) . The percentage of women who aborted in 24 h was also similar : 57/70 ( 81.4 % ) in the oral group and 58/69 ( 87.0 % ) in the vaginal group . Overall , 82.0 % of women preferred the oral route . Oral misoprostol ( 400 microg ) given every 3 h up to five doses , when combined with mifepristone , was as effective as the vaginal ( 200 microg ) route in second trimester termination of pregnancy . This regimen could also be offered to those women who found repeated vaginal administration unacceptable 9-Deoxo-16,16-dimethyl 9-methylene PGE2 was given as a vaginal suppository at 0 and 8 hours to 37 patients . Two different doses were given , a 75-mg and 60-mg dose . The larger dose achieved an 86 % abortion rate at 24 hours and for the smaller dose it was 53 % . When an intramuscular injection of 15-methyl PGF2 alpha Tham was added at 24 hours , the success rate was 91 % and 80 % at 36 hours . The incidence of gastrointestinal side effects were significantly reduced when compared to vaginal administration of either PGE2 or 15-methyl PGF2 alpha methyl ester . The incidence of temperature elevation was similar to that achieved with the use of vaginal PGE2 but higher than with the use of vaginal 15-methyl PGF2 alpha methyl ester We report the results of a large‐scale trial with mifepristonc ( RU 486 ) followed by the administration of a prostagl and in ( PG ) analogue for the medical termination of early pregnancy . Altogether , 16,173 patients from 300 centers were evaluated . 48 women ( 0.3 % ) were lost to follow‐up prior to , and 416 ( 2.6 % ) after the PG administration , and therefore the efficacy was evaluated in 15,709 women . Overall . the success rate was 95.3 % . with no statistical difference regarding the nature and dose of PG used . The median duration of bleeding was 8 days , being 12 days or less in 89.7 % of the women . Bleeding was significant cnough to necessitate a vacuum aspiration or a dilatation and curettage in 0.8 % of the cases . A blood transfusion was necessary in 0.1 % of the women ( 11 patients ) . Serious cardio‐vascular side‐effects were reported in 4 cases after the PG ( sulpro/tonc ) injection : they consisted of one acute myocardial infa rct ion attributed to a coronary spasm . and in marked hypotension in the other 3 woman . All patients recovered uneventfully . In conclusion , RU 486 followed by a PG analogue provides an efficient and safe medical alternative to surgery for early pregnancy termination , provided that the recommended protocol is adequately followed and the contraindications to prostagl and ins are respected OBJECTIVE The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination . STUDY DESIGN We performed a r and omized clinical trial in patients who were at 14 to 23 weeks of gestation and who were admitted for medical termination of pregnancy . All patients received 800 microg of vaginal misoprostol and were assigned r and omly to 400 microg of oral misoprostol or 400 microg of vaginal misoprostol every 8 hours . Efficacy and side effects were compared . The mean induction time of the study group was compared with that of an historic control group that had received 400 microg vaginally every 12 hours . RESULTS Forty-three women were assigned r and omly , 22 women to vaginal misoprostol and 21 women to oral misoprostol . Induction time and hospital stay were slightly shorter for the oral group ; however , the differences were not significant . Side effects were similar for both groups . CONCLUSION After an initial 800 microg dose of vaginal misoprostol , a regimen of 400 microg of oral misoprostol every 8 hours is as effective as the same dose of vaginal misoprostol with no additional side effects , which provides a convenient alternative for midtrimester pregnancy termination Sixty patients were r and omized to low-dose and high-dose groups , receiving a maximum total dose 1400 g of misoprostol by the vaginal route to compare the efficacy of the protocol s for second trimester termination of pregnancy . Outcome measures to be compared between the groups were success rates , time to termination , blood loss , complications and side-effects . Yet time to termination was significantly shorter in the high-dose than in the low-dose group ( 923 + /- 571 vs 1307 + /- 828 min ; p < 0.05 ) . The distance between the internal cervical os and the placenta was positively correlated with the duration of the termination process ( r = 0.508 , p < 0.001 ) . Induction to the fetal expulsion period is shorter with the higher dose without any significant increase in morbidity . A shorter distance between the internal cervical os and the placenta may forecast a shorter termination process OBJECTIVE The purpose of this study was to compare the clinical efficacy and side effects of 3 doses of intravaginal misoprostol for second-trimester pregnancy termination . STUDY DESIGN This was a prospect i ve r and omized , double-blind controlled clinical trial of 150 women who underwent pregnancy termination between 14 and 30 weeks of gestation . Three intravaginal misoprostol regimens were compared : 200 microg misoprostol at 6-hour intervals ( group 1 ) , 400 microg misoprostol at 6-hour intervals ( group 2 ) , and a loading dose of 600 microg misoprostol followed by 200 microg at 6-hour intervals ( group 3 ) . RESULTS There was a significant difference in the median time to achieve delivery among the 3 groups : group 1 ( 18.2 hours [ IQ , 13.3 - 32.5 hours ] ) vs group 2 ( 15.1 hours [ IQ , 10.9 - 23.7 hours ] ) vs group 3 ( 13.2 hours [ IQ , 11.2 - 21.7 hours ] ; P = .035 ) . Fifty-nine percent of the women in group 1 , 76 % of the women in group 2 , and 80 % of the women in group 3 delivered within 24 hours ( P = .013 ) . There were 7.8 % of the women in group 1 , 0 % of the women in group 2 , and 2 % of the women in group 3 who were undelivered at 48 hours ( P = .02 ) . There was an increase in the incidence of fever in the first 12 hours ( P = .038 ) and in the incidence of vomiting within 3 hours of the initial dose ( P = .048 ) in group 3 compared with the other groups . CONCLUSION Intravaginal misoprostol 400 microg at 6-hour intervals appears to be the preferred regimen for second-trimester pregnancy termination , with a shorter commencement to delivery interval than the 200 microg regimen and fewer maternal side-effects than the 600 microg loading dose regimen A prospect i ve r and omized trial was conducted in 148 women to compare the efficacy of two regimens of vaginal misoprostol for termination of second trimester pregnancy . Women aged 16 - 40 years requesting termination of second trimester pregnancy were r and omized into two groups . Women in group 1 were given vaginal misoprostol 400 microg every 3 h for a maximum of five doses in 24 h. Women in group 2 were given vaginal misoprostol 400 microg every 6 h for a maximum of three doses in 24 h. If women did not abort in 24 h , the same regimen was repeated . The median induction-abortion interval in group 1 ( 15.2 h ) was significantly shorter ( P < 0.01 ) than that in the group 2 ( 19.0 h ) . The percentage of women who achieved successful abortion within 48 h in group 1 ( 90.5 % ) was also significantly higher ( P < 0.02 ) than that in group 2 ( 75.7 % ) . The incidence of fever was more common in group 1 ( P = 0.01 ) . It is concluded that the regimen of vaginal misoprostol 400 microg every 3 h with maximum of five doses in 24 h was more effective than the regimen of misoprostol every 6 h in termination of second trimester pregnancy BACKGROUND The study was conducted to compare the efficacy and acceptability of second-trimester induction termination using vaginal misoprostol to hypertonic saline and d-cloprostenol , a prostagl and in F(2alpha ) ( PGF ) analogue , in Tashkent , Uzbekistan . STUDY DESIGN Eleven clinics providing second-trimester induction terminations were r and omized to provide one of two regimens for second-trimester induction termination : vaginal misoprostol 400 mcg every 3 h or hypertonic 10 % saline intrauterine instillation plus an intravenous PGF analogue , d-cloprostenol , 2.5 mg/h . Demographic information , and obstetric and medical history data were collected , and interviewers administered question naires to measure procedural pain and satisfaction . Differences in procedure time and complication rate , the primary outcomes , were analyzed with survival analysis and chi(2 ) tests . RESULTS Of 228 participants , 120 received misoprostol and 108 received hypertonic saline and d-cloprostenol ; the groups did not significantly differ by age , parity or gestational age . Both misoprostol and saline procedures were effective , with 99.2 % and 100 % successful abortion rates , respectively . Median procedure time ( 13.1 vs. 29.2 h , p<.001 ) , and number of women with retained placenta ( 2 vs. 70 , p<.001 ) or hemorrhage ( 3 vs. 19 , p=.001 ) were lower for the misoprostol group . Both provider ( p<.001 ) and patient ( p<.001 ) procedural satisfaction scores were higher for the misoprostol group . CONCLUSION While equally effective , vaginal misoprostol had a shorter time to abortion , was more acceptable to providers and patients and had fewer complications than saline instillation plus intravenous administration of a PGF analogue in Tashkent . This evidence supports change of the existing st and ard of care for second-trimester induction termination in Uzbekistan BACKGROUND To identify an effective misoprostol-only regimen for the termination of second trimester pregnancy , we compared sublingual and vaginal administration of multiple doses of misoprostol in a r and omized , placebo-controlled equivalence trial . METHODS Six hundred and eighty-one healthy pregnant women requesting medical abortion at 13 - 20 weeks ' gestation were r and omly assigned within 11 gynaecological centres in seven countries into two treatment groups : 400 microg of misoprostol administered either sublingually or vaginally every 3 h up to five doses , followed by sublingual administration of 400 microg misoprostol every 3 h up to five doses if abortion had not occurred at 24 h after the start of treatment . We chose 10 % as the margin of equivalence . The primary end-point was the efficacy of the treatments to terminate pregnancy in 24 h. Successful abortion within 48 h was also considered as an outcome along with the induction-to-abortion-interval , side effects and women 's perceptions on these treatments . RESULTS At 24 h , the success ( complete or incomplete abortion ) rate was 85.9 % in the vaginal administration group and 79.8 % in the sublingual group ( difference : 6.1 % , 95 % CI : 0.5 to 11.8 ) . Thus , equivalence could not be concluded overall ; the difference , however , was driven by the nulliparous women , among whom vaginal administration was clearly superior to sublingual administration ( 87.3 % versus 68.5 % ) , whereas no significant difference was observed between vaginal and sublingual treatments among parous women ( 84.7 % versus 88.5 % ) . The rates of side effects were similar in both groups except for fever , which was more common in the vaginal group . About 70 % of women in both groups preferred sublingual administration . CONCLUSIONS Equivalence between vaginal and sublingual administration could not be demonstrated overall . Vaginal administration showed a higher effectiveness than sublingual administration in terminating second trimester pregnancies , but this result was mainly driven by nulliparous women . Fever was more prevalent with vaginal administration . Registered with International St and ard R and omized Controlled Trial number IS RCT N72965671 OBJECTIVES To compare the effectiveness and safety of mifepristone/misoprostol versus intra-amniotic injection of ethacridine lactate for the termination of second trimester pregnancy . STUDY DESIGN 210 women requesting voluntary termination of pregnancies at between 16 and 24 weeks of gestation were r and omly assigned into two groups . Group 1 ( MM ) received a single oral dose of 200 mg mifepristone and , 36 - 48 h later , 400 microg of misoprostol vaginally , with up to three additional oral doses of 400 microg misoprostol every 12 h. Group 2 ( EL ) received an intra-amniotic injection of 100 mg ethacridine lactate . The primary outcome was successful abortion rate . Secondary outcomes included the difference in the induction-to-abortion interval and the frequency of adverse events . RESULTS Both MM and EL regimens were effective , with successful abortion rates of 96.19 % and 94.29 % , respectively ( P=0.746 ) . The complete abortion rates were 68.57 % and 70.48 % , respectively . The induction-to-abortion interval was longer in the MM group than in the EL group ( 50.57+/-6.80 h vs. 43.02+/-8.74 h , respectively , P<0.001 ) . Both treatments were safe , although there was a significant difference in rates of gastrointestinal and fever adverse events between the two groups . CONCLUSIONS Both MM and EL regimens were effective with high success rates and were safe for the termination of second trimester pregnancy In a r and omized , prospect i ve study at the Dept . of Obstetrics and Gynecology of the University Hospital of Giessen 4 different ways of inducing abortions with prostagl and ins were tested between the 15th and 24th week of gestation . The aim of the study was to determine the best approach to inducing abortion in order to minimize the psychological and physical stress to the patient . Subjects r and omized to the first two groups got a single cervical installation of either 0.5 mg Dinoprostongel ( Prepidil , N = 22 ) or 0.5 mg Sulprostongel ( Nalador , N = 21 ) . Six hours later , i.v . infusion with Sulproston ( 8.3 micrograms/min ) was started and continued until the abortion was complete . Patients r and omized to the third and fourth group received either 0.5 mg Dinoprostongel intracervically ( N = 15 ) or 1 mg Gemeprost vaginal suppositories ( Cergem , N = 21 ) every 6 hours until the cervix was 1 - 2 cm dilated . Subsequently the patients received an i.v . infusion with Sulproston until the abortion was complete . In the first group with intracervical application of Sulproston the total time until abortion was 17.8 h + /- 7.8 h. This was shorter than following a single application of Dinoprostongel ( 22.5 h + /- 14.7 h ) . Although there was a five hours difference , the between-group differences were not statistically different because of a wide range in values following Dinoproston treatment . This range could not be explained by the age of the mother , week of gestation or parity . In the group receiving multiple intracervical applications of Dinoproston the time till expulsion was twice as long as that after multiple vaginal suppositories of Gemeprost ( 33.8 h + /- 13.9 h vs. 15.6 + /- 6.0 h , p < 0.01 ) . The time span until a cervical dilatation of 1 - 2 cm was 27.0 h + /- 13.7 h in the group with repeated Dinoproston application . This period of time was more than twice the time span seen in the group with repeated Gemeprost application ( 12.5 h + /- 4.2 h , p < 0.01 ) . On the average four treatments with intracervical Dinoprostongel were required while the average with Gemeprost vaginal suppositories was two to achieve a cervical dilatation of 1 - 2 cm . Furthermore in 7 of 21 cases treatment with Gemeprost achieved the expulsion of the fetus without Sulproston infusion ( 11.4 h + /- 5.2 h ) . Comparing single versus repetitive prostagl and in application we could demonstrate that the duration of Sulproston infusion was cut in half after repeated therapy with Gemeprost . We conclude that repetitive application of Gemeprost vaginal suppositories decreases the time to abortion and subject discomfort tremendously . The application of Gemeprost suppositories provides the easiest and most efficient therapeutic approach for both patients and staff . Furthermore the regiment that provided the best results was also the most cost-effective ( range 180,-DM to 317,- DM per case ) BACKGROUND Sublingual misoprostol has been shown to be effective in medical abortion . A prospect i ve double-blinded placebo-controlled trial was done to compare the efficacy and side-effects of sublingual to oral misoprostol when used with mifepristone for medical abortion from 12 to 20 weeks gestation . METHODS A total of 120 women at 12 - 20 weeks of gestation were r and omized to receive 200 mg oral mifepristone followed by either sublingual or oral misoprostol 400 mg every 3 h for a maximum of five doses 36 - 48 h later . The course of misoprostol was repeated if the woman did not abort within 24 h. RESULTS There was no significant difference ( P = 0.43 ) in the success rate at 24 h [ relative risk = 1.075 ; 95 % confidence interval ( CI ) : 0.94 - 1.19 ] . Abortion occurred in 91.4 % in the sublingual group ( 95 % CI : 81.0 - 96.7 % ) as compared to 85.0 % ( 95 % CI : 73.7 - 92.1 % ) in the oral group . The median induction-to-abortion interval was significantly shorter ( P = 0.009 ) in the sublingual group ( 5.5 h ) as compared to the oral group ( 7.5 h ) . The incidence of fever was higher in the sublingual group ( P < 0.0001 ) . The incidences of other side-effects were similar . CONCLUSION Sublingual misoprostol , when combined with mifepristone , is effective for medical abortion in the second trimester . The induction-to-abortion interval is shorter when sublingual misoprostol is used when compared to oral misoprostol Summary Gemeprost ( Cervagem ) has been used widely compared with Misoprostol ( Cytotec ) alone in second trimester pregnancy termination . This prospect i ve r and omised trial was to evaluate the efficacy of intravaginal Misoprostol ( alone ) and Gemeprost in second trimester termination of pregnancy . A total of 54 women with 27 on each arm were involved . A total of 25 patients ( 92.6 % ) in the Misoprostol group and 22 patients ( 81.5 % ) in the Gemeprost group delivered within 48 h. The Misoprostol group delivered earlier , although average number of tablets required were similar . The side-effects were not significant between the two groups in fact , but there was more pyrexia in the Gemeprost group ( p = 0.004 ) . Misoprostol in second trimester termination of pregnancy is clinical ly as effective and less costly than the st and ard regimen of Gemeprost The object of this study was to compare intravaginal misoprostol and dinoprostone ( prostagl and in E2 ) for second-trimester pregnancy termination , and to examine the role of the nitric oxide donor , glyceryl trinitrate , as a possible alternative to prostagl and ins to induce cervical ripening in second-trimester pregnancy termination . This was a r and omised clinical trial . The trial involved pregnant women between 13 and 28 weeks ' gestation admitted with clear medical or obstetric indications for pregnancy termination , and was carried out in the department of obstetrics and gynecology , Assiut University Hospital , Egypt . Patients were classified into Group A , where pregnancy termination was induced by vaginal misoprostol 100 micrograms every 4 hours with a maximum dose of 500 micrograms ; Group B , where induction was by vaginal dinoprostone 6 mg every 6 hours with a maximum dose of 24 mg ; and Group C , where induction involved vaginal glyceryl trinitrate 500 micrograms every 6 hours with a maximum dose of 2.5 mg . Twenty-four hours after the start of induction , the rate of complete abortion in the three groups was 100 % , 66.67 % and 0 % , respectively . The rate of complete abortion was 100 % in the nitric oxide ( glyceryl trinitrate)-induced group after introducing a complementary procedure . The induction – abortion interval was significantly shorter , the number of doses needed was less and the maximum Bishop score reached was greater with misoprostol than with dinoprostone . A higher rate of side effects occurred with the misoprostol-induced group ( 74 % ) compared with the other two groups ( 46.6 % and 0 % ) . Misoprostol is a cheap , effective drug for second-trimester pregnancy termination with short induction abortion intervals but a higher rate of side effects . Prostin E2 is also effective in termination of second-trimester pregnancy but is expensive and may require high doses to be administered . Glyceryl trinitrate is an effective drug for cervical ripening ( softening ) but it has no role in the stimulation of uterine contractions OBJECTIVE This study was undertaken to compare the efficacy and side effects of a high-dose vaginal misoprostol regimen to concentrated intravenous oxytocin plus low-dose vaginal misoprostol for midtrimester labor induction . STUDY DESIGN Women at 14 to 24 weeks , with obstetric or fetal indications for delivery and no prior cesarean , were r and omly assigned to receive either vaginal misoprostol 600 microg x 1 , then 400 microg every 4 hours x 5 ( group 1 ) or escalating dose-concentrated oxytocin infusions ( 277 - 1667 mU/min ) plus vaginal misoprostol 400 microg x 1 , then 200 microg every 6 hours x 2 , then 100 microg x 1 ( group 2 ) . Analysis was by intent to treat . Primary outcomes were live birth rate and induction-to-delivery interval . RESULTS The intended sample size was 70 women per group ; however , the trial was terminated at the initial interim analysis because of a highly significant difference in 1 of the primary study outcomes . Twenty women were assigned to group 1 and 18 were assigned to group 2 . Median induction-to-delivery interval was significantly shorter in group 1 ( 12 hours , range 4 - 44 hours ) versus group 2 ( 18 hours , range 7 - 36 hours ; P = .01 ) . Induction success rate at 12 hours was significantly higher in group 1 ( 60 % ) compared with group 2 ( 22 % , P = .02 ) . No significant difference was noted in the live birth rate between groups 1 and 2 ( 13 % , 0 % , P = .16 ) . The incidence of retained placenta requiring curettage , chorioamnionitis , intrapartum fever , nausea , emesis , and diarrhea were similar between both groups . CONCLUSION Compared with concentrated oxytocin plus low-dose vaginal misoprostol , high-dose vaginal misoprostol significantly shortens midtrimester labor inductions BACKGROUND Progesterone is central to the maintenance of pregnancy , and is thus the ideal target for fertility regulation . Two mechanisms by which progesterone can be targeted are : receptor blockade and reduction of progesterone production through enzyme inhibition . Mifepristone , a receptor blocker , is usually given as ' pretreatment ' prior to prostagl and in administration in mid-trimester termination of pregnancy ( TOP ) . Unfortunately , there are difficulties accessing mifepristone in developing countries , and TOP is therefore performed using prostagl and ins alone , which results in unacceptably long induction-to-abortion intervals . Trilostane is a 3beta-hydroxysteroid dehydrogenase inhibitor which reduces progesterone production . In these mid-trimester studies it is evaluated as a method of pretreatment prior to misoprostol administration . METHODS Three consecutive r and omized controlled trials comparing different trilostane regimens for pretreatment were performed . In study 1 , trilostane was compared with placebo ; in study 2 , two doses of trilostane were compared ( 1080 mg and 720 mg ) ; in study 3 , the effect of adding danazol to trilostane as combination therapy was evaluated . The primary outcome in all the studies was the induction-to-abortion interval . Serum progesterone , estradiol and cortisol were measured serially during treatment . RESULTS In study 1 , 48 women were r and omized . The median induction-to-abortion interval was 9 h in the trilostane group and 18.5 h in the placebo group ( P < 0.0001 ) . Progesterone and estradiol production was significantly reduced in the women receiving trilostane , with maintenance of diurnal cortisol variation . Twenty-eight women were r and omized in study 2 , which demonstrated that there was no significant difference in the induction-to-abortion interval using 1080 mg and 720 mg trilostane when compared with the higher doses used in study 1 . Study 3 , in which 40 women were included , failed to show any additional benefit using combination therapy with danazol and trilostane . CONCLUSIONS Trilostane is an effective pretreatment agent in mid-trimester TOP Objective To compare the effectiveness of vaginal misoprostol administered 6 or 12 hourly for second trimester pregnancy termination The objective of this work was to study the abortifacient effects of misoprostol , an orally active prostagl and in E1 ( PGE1 ) analogue , in the second trimester . A r and omized study of two prostagl and in regimens in women pre-treated with the antiprogesterone mifepristone was carried out in the gynaecological wards of Aberdeen Royal Hospitals , NHS Trust , and included 60 women at 13 - 20 weeks ' gestation , in whom termination of pregnancy had been agreed . Following pre-treatment with mifepristone 600 mg women were r and omly allocated to one of two prostagl and in regimens which started 36 - 48 h later . The first misoprostol 400 micrograms orally ( up to three doses ) followed by gemeprost vaginal pessary 1 mg up to two doses . The second was gemeprost vaginal pessary 1 mg up to five doses . The main outcome measures were success rate induction-to-abortion interval and side-effects . There were no significant differences between the two groups in any of the main outcome measures . We conclude that misoprostol is a stable , cheap PGE1 analogue with demonstrable efficacy and acceptable side-effects in the management of second trimester abortion . Further work is needed to establish the optimum dose and regimen OBJECTIVE To evaluate the induction-to-abortion time of 3 pharmacokinetic-based protocol s at 13 - 20 weeks of gestation . STUDY DESIGN A r and omized trial was conducted on 153 patients . The oral group ( n = 51 ) received 100 microg misoprostol orally every 2 hours , the vaginal group ( n = 51 ) received 200 microg misoprostol vaginally every 4 hours , and the sublingual group ( n = 51 ) received 100 microg misoprostol sublingually every 2 hours . RESULTS The mean induction-to-delivery time was shorter in the sublingual group ( mean , 651 + /- 507 ) as compared to the vaginal group ( mean , 1,056 + /- 634 , p = 0.01 ) . The number of patients who delivered within 12 hours was significantly higher in the sublingual group ( n = 39 , 78 % ) as compared to the oral ( n = 26 , 52 % ) and vaginal ( n = 20 , 40 % ) groups ( p < 0.001 ) . The numbers of patients who delivered within 24 hours were comparable in the sublingual ( n = 47 , 94 % ) and oral ( n = 46 , 92 % ) groups but higher than in the vaginal group ( n = 39 , 78 % ; p = 0.02 ) . The total misoprostol dose was 543 + /- 422 microg in the sublingual group , 878 + /- 533 microg in the vaginal group and 741 + /- 413 microg in the oral group ( p < 0.001 ) . CONCLUSION A pharmacokinetic-based application of 100 microg of sublingual misoprostol every 4 hours is more effective for induction of second-trimester abortion as compared to 100 microg oral misoprostol every 2 hours and 200 microg vaginal misoprostol every 4 hours Objective : To compare the efficacy of a combined regimen of misoprostol with vaginal misoprostol for early 2nd-trimester pregnancy termination . Methods : This is a prospect i ve study that includes 79 pregnant women who requested legal termination of 2nd-trimester pregnancy between 13 and 22 weeks . Two regimens of misoprostol were used . Group 1 : 400 µg of oral plus 400 µg vaginal misoprostol every 8 h ( combined regimen ) and group 2 : 400 µg of vaginal misoprostol every 3 h up to a maximum of five doses ( vaginal regimen ) . Results : The induction-to-abortion interval was significantly longer in group 1 ( 25.5 ± 24.45 h ) than in group 2 ( 15 ± 7.14 h ) ( p = 0.016 ) . The abortion rate within 24 h in group 1 was of 56.8 vs. 85.7 % in group 2 ( p = 0.006 ) . The hazard rate for vaginal delivery within 24 h was found to be 2.277-fold greater in the group with the combined therapy once controlled for plausible confounders . Conclusions : Our study suggests that oral misoprostol combined with vaginal misoprostol does not reduce the induction-to-abortion interval compared to an exclusively vaginal route when used for early 2nd-trimester pregnancy termination OBJECTIVE The aim of the study was to compare the consistency of major/minor fetal anomalies detected by second trimester prenatal ultrasound examination with the findings in fetal autopsies following the termination of pregnancy ( TOP ) in the second trimester . DESIGN In a 4-year long prospect i ve study , 107 second-trimester TOP was performed due to fetal malformation diagnosed by second trimester-ultrasound examination at a tertiary referral center . Ultrasound findings were compared with fetal autopsy findings . RESULT Of the 107 cases with major fetal anomalies diagnosed by prenatal ultrasound , 49 % had central nervous system anomalies , 23 % had kidney and urinary tract anomalies , 11 % had congenital heart disease . All of these major anomalies leading to TOP were confirmed by fetal autopsy ( 100 % success rate in major anomalies ) . Overall success rate in prenatal ultrasound for major and minor anomalies was 77 % . The percentage of additional minor anomalies detected in fetal autopsies was 20 % . Three percent of the minor anomalies detected by prenatal ultrasonography could not be confirmed during autopsy . Chromosomal anomalies were detected in 9 ( 16 % ) out of 57 cases . CONCLUSION Evaluation of fetal autopsies following TOP enables diagnosis of pathologies undetected by prenatal ultrasound alone , leading to better preconceptional counseling for subsequent pregnancies A study was conducted in Calcutta , India , to evaluate and compare the safety and effectiveness of the intraamniotic instillation of 5 % and 20 % saline in 359 women undergoing midtrimester pregnancy termination . The two abortion techniques were r and omly assigned to the study patients . The incidence of method failures in the 5 % ( 9.4 % ) and 20 % ( 7.2 % ) saline groups was not significantly different ( p less than 0.05 ) , nor was the incidence of incomplete abortion rates for the two groups significantly different ( p less than 0.05 ) . At 24 hours or less , the abortion rates were significantly higher ( p less than 0.05 ) for women receiving the 20 % saline , but at 36 and 48 hours there was no significant difference ( p less than 0.05 ) . The mean induction-to-abortion interval was higher for the 5 % ( 30.1 hours ) than for the 20 % ( 28.8 hours ) saline cases , but this was not significantly significant . The incidences of excessive blood loss and fever were significantly higher ( p less than 0.05 ) for patients receiving the 5 % than for those receiving the 20 % saline . There were five ( 2.4 % ) deaths among the 20 % and one death ( 0.7 % ) among the 5 % saline groups OBJECTIVE Detection of congenital heart defects by prenatal ultrasound examination has been one of the great challenges since the investigation for fetal anomalies became part of the routine fetal examination . This prospect i ve study was design ed to evaluate the concordance of prenatal ultrasound findings with autopsy examination in a population consisting of both referred women and non-selected pregnant women . DESIGN Criteria for inclusion were an ultrasound examination at the National Center for Fetal Medicine and an autopsy performed during the years 1985 - 94 . Results from the ultrasound and autopsy examinations were systematized into categories depending on the degree of concordance . RESULTS Of 408 infants and fetuses with developmental anomalies , 106 ( 26 % ) had congenital heart defects . In 63 ( 59 % ) of these 106 cases , the heart defect was the principal reason for the termination of pregnancy or the cause of death . Excluding five cases with a secundum atrial septal defect , there was complete agreement between the ultrasound examination and the autopsy findings in 74 ( 73 % ) of 101 cases . In 18 cases , there were minor discrepancies between ultrasound and autopsy findings . The main diagnosis was thus correct in 92 cases ( 91 % ) . From the first time period ( 1985 - 89 ) to the second ( 1990 - 94 ) , the detection rate of all heart defects increased from 48 % to 82 % . CONCLUSION This study confirms a good correlation between ultrasound and autopsy diagnoses in fetuses and infants with congenital heart defects . A significant improvement in the detection of heart defects occurred from the first time period to the second and was probably due to increased experience and technical advances Objective To compare the efficacy of vaginal with oral misoprostol in termination of second-trimester pregnancy after pretreatment with mifepristone . Methods Women requesting termination of secondtrimester pregnancy were r and omized into two groups . Thirty-six to 48 hours after oral administration of 200 mg of mifepristone , women were given either oral or vaginal misoprostol 200 μg every 3 hours for a maximum of five doses in the first 24 hours . Women receiving oral misoprostol also were given a vaginal placebo ( vitamin B6 ) , whereas those receiving vaginal misoprostol were given an oral placebo . If they failed to abort , a second course was given by the same route . Results The median induction-abortion interval in the vaginal group ( 9 hours ) was significantly shorter than that in the oral group ( 13 hours ) . The percentage of women aborting within 24 hours in the vaginal group ( 90 % ) was significantly higher than that in the oral group ( 69 % ) . The median amount of misoprostol used in the vaginal group ( 600 μg ) also was significantly less than that in the oral group ( 1000 μg ) . There was no significant difference in the incidence of side effects between the two groups except for fatigue and breast tenderness , which were more common in the oral group . Seventy-six percent of the women preferred the oral route , and 24.5 % of the women preferred the vaginal route . Conclusion Vaginal misoprostol is more effective than oral misoprostol in termination of second-trimester pregnancy after pretreatment with mifepristone , but more women preferred the oral route Objective To compare the use of 600 and 200 mg mifepristone prior to second trimester termination of pregnancy with the prostagl and in misoprostol The use of gemeprost ( 16,16 dimethyl-PGE1-methyl ester ) pessaries was compared in an open , r and omized single-centre trial with the intra-amniotic injection of PGF2 alpha combined with hypertonic saline , intravenous oxytocin and a hygroscopic cervical dilator ( Dilapan ) for the termination of pregnancy between 14 and 20 weeks . There was no significant difference in the induction-delivery interval for the two groups . With the exception of an increased incidence of diarrhoea in the gemeprost group , there was no significant difference in other side effects , analgesic requirements or retained placentae . Gemeprost pessaries are an effective alternative to the more invasive methods previously used for the induction of second-trimester termination A prospect i ve r and omized study was conducted to compare the efficacy of misoprostol with gemeprost when combined with mifepristone for termination of second trimester pregnancy . Patients requesting termination of second trimester pregnancy were r and omized into two groups . In both groups of patients , 200 mg of mifepristone was given 36 to 48 hours before the administration of prostagl and ins . In Group 1 , the women were given 400 micrograms of oral misoprostol every 3 hours up to 5 doses . In Group 2 , patients were given 1 mg of vaginal gemeprost every 6 hours up to 4 doses . The main outcomes measured were the induction-abortion intervals ( the interval between the first dose of prostagl and in and abortion ) and the incidence of side effects . Altogether , 50 subjects were recruited with 25 women in each group . The mean age and parity of the women and the mean gestational age of the two groups of women were comparable . There was no significant difference in the median induction-abortion intervals ( 8.7 hours in Group 1 and 10.8 hours in Group 2 ) or the incidence of side effects between the two groups of patients . We conclude that misoprostol is as effective as gemeprost in termination of second trimester pregnancy when combined with mifepristone A prospect i ve r and omised controlled trial was undertaken to compare the efficacy of two routes of administration , oral versus vaginal , of the prostagl and in El analogue misoprostol ( Cytotec ) to effect termination of pregnancy in the mid‐trimester For the purpose of reducing the side effects and complication rate when inducing second trimester abortion , intracervically administered PGE2 gel was tested for the first time and compared with a single intraamniotic instillation of PGF2 alpha by a r and omized allocation of 41 consecutive patients in the 13th to 24th week of gestation . In both groups the treatment was supplemented with oxytocin 5 - 6 hours after starting the induction . The methods proved of equal value as regards the abortion success rate and the induction-abortion interval , whereas the incidence of gastrointestinal side effects on intracervical application of PGE2 gel was only half as high and the occurrence of diarrhea significantly lower ( p less than 0.05 ) with this non-invasive method than with intraamniotic PGF2 alpha . Intracervical PGE2 gel also possessed other advantages , being int . al. more acceptable by the patients and technically easier to administer The safety and effectiveness of two intraamniotic prostagl and in F2alpha ( PGF2alpha ) dose schedules ( a single 50 mg dose and a repeated 25 mg dose ) and intraamniotic hypertonic saline were evaluated in a study where each abortion procedure was r and omly assigned to 50 patients . All patients were at 16 to 20 weeks ' gestation . Rates of gastrointestinal and other side effects were generally higher for the 50 mg PGF2alpha dose schedule than for the other two procedures . The repeated 25 mg PGF2alpha dose schedule result ed in higher 24-hour ( 68.0 % ) and 48-hour ( 98.0 % ) cumulative abortion rates than the 50 mg PGF2alpha dose schedule ( 54.0 % , 92.0 % ) or saline ( 34.7 % , 91.8 % ) . Rates of spontaneous placental expulsion were highest for the repeated 25 mg PGF2alpha dose ( 74.0 % ) and lowest for the 50 mg PGF2alpha dose schedule ( 40.0 % ) Abortion during mid-pregnancy was performed in 200 patients by extra-amniotic insertion of Nelaton catheters and instillation of 0.1 % rivanol solution . To shorten the abortion time , quinine hydrochloride was given orally in one group ( n=100 ) , and intravenous infusion of prostagl and in F2 alpha ( PGF2 alpha ) was undertaken in the other group ( n=100 ) . The abortion rate after 72 hours was higher in the PGF2 alpha group ( 96 % ) than that in the quinine group ( 91 % ) , but the difference was not statistically significant . The abortion time was significantly shorter in the PGF2 alpha group than in the quinine group ( p less than 0.01 ) . This method , together with supplementary treatment with oxytocic substances , proved to be an effective mid-pregnancy abortion method . The risks of endometritis , gastro-intestinal complications , and /or heavy bleeding either during or post-abortive were minimal BACKGROUND The conventional timing of misoprostol administration after mifepristone for second trimester medical abortion is 36 - 48 h , but simultaneous administration , which may make the regimen more convenient , has not been studied . The objective of this r and omized comparison study is to compare two intervals of administration of misoprostol after pretreatment with mifepristone for second trimester medical abortion . METHODS Eligible women with gestational age between 12 and 20 weeks were r and omized to receive mifepristone 200 mg orally followed by 600 microg misoprostol vaginally either immediately or 36 - 38 h later , followed by 400 microg vaginal misoprostol every 3 h for a maximum of four doses . The primary outcome measure was the success rate at 24 h after the start of misoprostol treatment and the secondary outcome measures were the induction-to-abortion interval and the frequency of side effects . RESULTS There was a significant difference in the success rate at 24 h ( 36 - 38 h : 100 % ; immediate : 91.5 % ) . The median induction-to-abortion interval was significantly shorter in the 36 - 38 h regimen ( 4.9 h ) compared with the immediate regimen ( 10 h ) . Side effects in terms of febrile episodes and chills/rigors were significantly higher in the immediate administration group . CONCLUSIONS Simultaneous use of mifepristone and misoprostol for second trimester medical abortion is not as effective as the regimen using a 36 - 38 h dosing interval Objectives To compare the efficacy of repeated doses of 100 μg vs. 200 μg misoprostol given sublingually for induction of second trimester abortion . Methods One hundred and sixty-two women at 15–22 weeks ' gestation were r and omized to receive every 2 h either 100 μg ( group 1 ; n = 81 ) or 200 μg ( group 2 ; n = 81 ) misoprostol sublingually . The primary outcome measure was the abortion rate within 24 h. The secondary outcome measures were the induction-abortion interval , the total misoprostol dose required , and side effects of the regimen . Results There was no significant difference between the two groups with regard to the abortion rates within 12 h ( 43.2 % in group 1 vs. 48.1 % in group 2 ; p = 0.52 ; relative risk [ RR ] : 0.81 ; 95 % confidence interval [ CI ] : 0.4–1.5 ) and 24 h ( 92.6 % in group 1 vs. 91.4 % in group 2 ; p = 0.77 ; RR : 1.11 ; 95 % CI : 0.37–3.6 ) . The induction-abortion intervals in the two groups were of similar length ( 885 minutes in group 1 vs. 912 minutes in group 2 ; p = 0.72 ) . When the total dose of misoprostol was compared between the two groups , women belonging to group 2 on average had received significantly more misoprostol than those in group 1 ( 1274 ± 592 μg [ 7 ± 3 doses ] vs. 614 ± 432 μg [ 6 ± 4 doses ] , respectively ; p = 0.000 ) . Conclusions Sublingual administration of repeated doses of 100 μg misoprostol for abortion induction appears to be equally effective to that of repeated doses of 200 μg OBJECTIVE Our purpose was to compare the efficacy of oral misoprostol with that of vaginal misoprostol for midtrimester termination of pregnancy . STUDY DESIGN Women seen for midtrimester pregnancy termination were r and omly assigned to receive either misoprostol orally in a dose of 200 microg every hour for 3 hours followed by 400 microg every 4 hours or vaginally in a dose of 400 microg every 4 hours . The protocol was followed for 24 hours , after which time further management was at the discretion of the attending physician . The primary outcome measure was the induction-to-delivery interval . Sample size was calculated a priori . Statistical analysis was performed with the t test for continuous variables and the chi(2 ) test for categorical variables . P < .05 was considered significant . RESULTS One hundred fourteen women were r and omized , with 49 receiving vaginal misoprostol and 65 receiving oral misoprostol . The two groups were comparable with respect to maternal age , parity , indication for pregnancy termination , gestational age , and maternal weight . The mean induction-to-delivery interval was significantly shorter for the vaginal group ( 19.6 + /- 17.5 hours vs 34.5 + /- 28.2 hours , P < .01 ) . Length of stay was also shorter in the vaginal group ( 32.3 + /- 17.3 hours vs 50.9 + /- 27.9 hours , P < .01 ) . Significantly more patients in the vaginal group were delivered within 24 hours ( 85.1 % vs 39.5 % , P < .01 ) , and more patients in the oral group required changes in the method of induction when they were undelivered after 24 hours ( 38.2 % vs 7 % , P < .01 ) . The only complication was an increase in febrile morbidity in the vaginal group ( 25 % vs 6.7 % , P = .046 ) . This did not result in an increased use of antibiotics , and all the fevers resolved post partum without further complications . CONCLUSIONS Vaginal administration of misoprostol result ed in a shorter induction-to-delivery interval . The shorter length of stay should result in improved patient care The management of second-trimester abortion is still not satisfactory with respect to safety and side-effects ; it is considered to be in a state of evolution . The goal of this investigation has been to combine , in reduced quantity , prostagl and in and hypertonic saline in order to minimize the complications and side-effects associated with the separate administration of each component . This study documents the results of a r and om sample of 385 abortions performed in the second trimester , induced by intra-amniotic instillation of prostagl and in ( 20 mg ) and NaCl 5 and 10 g in different volumes and concentrations augmented with oxytocin . In a series of 20 patients , the coagulation profile is presented and the clinical characteristics of 4 groups are compared . This study demonstrated no coagulation defects . The gastrointestinal side-effects were reduced . In spite of the reduced dosage of each component , the instillation abortion interval still remained 17.08 h on the average . Incomplete abortion ranged from 32 % to 48.78 % . The data presented in this report suggests that combination of prostagl and in , hypertonic saline and oxytocin is feasible for midtrimester abortion It is well established that abortion can be induced successfully in midtrimester of pregnancy by gemeprost vaginal pessaries . A r and omised study was carried out to determine the efficacy of mifepristone and dilapan in combination with gemeprost for second trimester termination between 12 - 18 weeks ' gestation . A contemporary group of women treated with gemeprost alone was used as a control group . A single course of 4 x 1 mg gemeprost pessaries was administered every six hours . If abortion had not occurred after 24 hours , a further course of 5 x 1 mg pessaries was administered every three hours over the next 24 hours . In the first twenty hours after administration of gemeprost , 95 % , 85 % and 72 % of women aborted in the mifepristone , dilapan and the control group , respectively . The median induction-abortion interval in the mifepristone group ( 6.6h ) was significantly shorter than the other two groups and fewer pessaries were required to induce abortion . The incidence of diarrhoea and vomiting was lower in the mifepristone than the other two study groups . This study demonstrated the efficacy of mifepristone in combination with gemeprost and this regimen is associated with fewer gastrointestinal side effects The combination of mifepristone ( RU486 ) and prostagl and in is effective in the induction of abortion in the second trimester . The optimal regimen is still under development , but is likely to be characterized by a short induction-to-abortion interval , low incidence of side-effects and high acceptability . We have investigated further whether misoprostol , a synthetic prostagl and in E1 analogue , can reliably induce second trimester abortion in 70 women pre-treated with mifepristone , and whether different routes of administration affect the induction-to-abortion interval . Abortion was achieved in 97 % [ 95 % confidence interval ( CI ) 90 - 100 % ] of cases without resort to other prostagl and in agents . The mean induction abortion time for the studied population was 6.4 h ( 95 % CI 5.6 - 7.0 h ) . No significant difference was found between two different routes of administration , namely vaginal versus a combination of vaginal and oral . Misoprostol has a number of advantages over other prostagl and in preparations . We recommend that , following pre-treatment with mifepristone , misoprostol is used as the prostagl and in of choice to induce abortion in the second trimester Objective To compare the efficacy , side effects and acceptability of sublingual and vaginal misoprostol for second trimester medical abortion OBJECTIVE To determine the more applicable of two ways of prostagl and in induction currently in use in second trimester induced abortions for congenital or chromosomal abnormalities . DESIGN A prospect i ve r and omised controlled trial . SETTING Department of Obstetrics and Gynaecology , Tygerberg Hospital , CP . STUDY POPULATION Twenty consecutive patients admitted for termination of pregnancy for congenital or chromosomal abnormalities between 14 and 26 weeks ' pregnancy duration . MANAGEMENT Patients were r and omly selected to receive either 1.5 mg prostagl and in E2 ( PGE2 ) gel extra-amniotically or 25 mg prostagl and in F2 alpha ( PGF2 alpha ) intra-amniotically . Patients in both groups received oxytocin to a maximum dosage of 120 mU per minute if they had not aborted 18 hours after the original administration of either prostagl and in regimen . If abortion had not taken place 36 hours after commencement of treatment , management was considered unsuccessful . MAIN OUTCOME MEASUREMENTS Proportion of successful inductions and complications . RESULTS Complications of management were rare and did not differ between the two management groups . However , there were significantly more failures in the group who received intra-amniotic PGF2 alpha ( 7 v. 2 patients ) as well as a significantly higher need for oxytocin in this group ( 10 v. 4 patients ) . CONCLUSIONS With promising drugs such as prostagl and in analogues and anti-progesterones not universally available , methods of induction suitable to the local situation should be sought . Extra-amniotic PGE2 seems more suitable than intra-amniotic PGF2 alpha because of a shorter induction-to-delivery time without increased morbidity Background . A comparison of ethacridine lactate and prostagl and in E2 ( PGE2 ) with or without oxytocin infusion in second trimester medical abortion cases Objective . To compare two methods for second trimester termination of pregnancy : mifepristone and misoprostol versus Dilapan ® and sulprostone . Methods . This was a r and omized study involving 16 patients with a singleton live fetus with congenital malformations or genetic disorders . Eight patients were treated with 200 mg mifepristone orally followed by 200 μg misoprostol vaginally 3 hourly and eight patients received a sulprostone infusion after cervical dilatation with Dilapan . Results . Mifepristone and misoprostol had a mean induction interval of 17.8 hours and sulprostone and Dilapan 20.9 hours . The mean induction interval did not differ significantly . Mean hospital stay was shorter in the patients treated with misoprostol : 2.1 vs. 3.3 days ( p = 0.02 ) with a 95 % confidence interval of −2.1 to 0.3 . Conclusion . Mifepristone and misoprostol did not reduce the induction interval significantly compared to the sulprostone and Dilapan treatment for second trimester pregnancy termination . Hospital admission was significantly shorter in patients treated with mifepristone and misoprostol OBJECTIVE To compare the clinical efficacy and side effects of oral misoprostol with vaginal misoprostol for second-trimester pregnancy termination . METHODS A r and omized clinical trial of medical pregnancy termination between 14 and 26 weeks ' gestation was conducted . Three misoprostol regimens were compared : 400 μg vaginally at 6-hour intervals ( group 1 ) , 400 μg orally at 3-hour intervals ( group 2 ) , and a loading dose of 600 μg vaginally followed by 200 μg orally at 3-hour intervals ( group 3 ) . A sample size of 225 women was required for equivalence of the three regimens , with an interim safety analysis planned at 80 women . RESULTS A significant difference between the groups was evident at the interim safety analysis and the study ceased . The subset of 84 women recruited before the study closure is described . There was a significant difference in the median time to achieve delivery among the three groups : group 1 , 14.5 hours ( 95 % confidence interval 12.0 , 16.9 ) , versus group 2 , 25.5 hours ( 13.5 , 23.8 ) , versus group 3 , 16.4 hours ( interquartile range 14.2–37.3 ) ( P = .042 ) . Within 24 hours of commencement 85.7 % of women in group 1 , 44.8 % in group 2 , and 74.1 % in group 3 delivered ( P = .003 ) . At 48 hours 0 % in group 1 , 20.7 % in group 2 , and 3.7 % in group 3 were undelivered ( P = .011 ) . There was no difference in women 's perceptions of the termination process . CONCLUSION In second-trimester pregnancy termination , a vaginal misoprostol regimen of 400 μg every 6 hours was 1.9 times more likely to result in delivery within 24 hours from commencement than an oral regimen of 400 μg every 3 hours Objective To compare the pharmacokinetics of vaginal and oral administration of the prostagl and in E1 analogue , misoprostol . Methods Twenty women received 400-μg doses of misoprostol either orally or as tablets placed in the vagina . Serum levels of the principal metabolite , misoprostol acid , were measured at 7.5 , 15 , 30 , 45 , 60 , 90 , 120 , and 240 minutes . The first ten women were pregnant and undergoing firsttrimester abortions , and the last ten were not pregnant and had additional blood sampling at 360 minutes . We compared the pharmacokinetics of misoprostol acid after oral and vaginal administration . Results All 20 subjects completed the study . The maximum mean ( ± st and ard deviation [ SD ] ) of misoprostol acid differed significantly between the oral and vaginal groups ( 277 ± 124 compared with 165 ± 86 pg/mL , respectively ; P = .03 , analysis of variance ) , as did the mean ± SD time to peak levels ( 34 ± 17 compared with 80 ± 27 minutes , respectively ; P < .001 ) and areas under the misoprostol concentration versus time curve ( mean ± SD ) up to 4 hours ( n = 20 , 273.3 ± 110.0 compared with 503.3 ± 296.7 pg . hour/mL , respectively ; P = .033 ) and up to 6 hours ( n = 10 , 300.0 ± 103.3 compared with 956.7 ± 541.7 pg . hour/mL , respectively ; P = .029 ) . The extent of absorption was highly variable among subjects in each group . Conclusion There are significant differences in the pharmacokinetics of misoprostol administered by vaginal and oral routes that may explain the difference observed in clinical efficacy . Assuming that the pharmacologic effect of misoprostol is related to its concentration in the plasma , our observation of the prolonged serum concentrations in the vaginal group suggests that vaginal administration could be dosed at longer intervals than oral OBJECTIVE To determine the efficacy of a new dose regimen of vaginal gemeprost ( 1 mg every 6 h up to three doses ) in induction of abortion in women less than or equal to 56 days gestation , and to compare this regimen with mifepristone ( 200 - 600 mg ) followed 48 h later by a single dose of gemeprost ( 1 mg ) . DESIGN Two separate protocol s , with 50 % of the subjects r and omized to one or other protocol . SETTING The Royal Infirmary of Edinburgh , Scotl and , UK . SUBJECTS 301 referred by their general practitioner or local family planning clinic , requesting termination of pregnancy at less than or equal to 56 days amenorrhoea . INTERVENTIONS Ongoing pregnancies and incomplete abortions were terminated surgically . MAIN OUTCOME MEASURES Number of complete abortions , analgesic requirements and bleeding pattern following treatment . RESULTS Complete abortion occurred in 87 % of women treated with gemeprost alone and 98 % of women treated with mifepristone and gemeprost ( P = 0.0004 ) . Analgesic requirements were greater in the group treated with gemeprost alone , compared with the group treated with mifepristone and gemeprost ( P = 0.0001 ) . CONCLUSION The new dose regimen of gemeprost can be used for early induced abortion , but the use of mifepristone and gemeprost has several advantages over the use of gemeprost alone OBJECTIVE To examine the efficacy of vaginal misoprostol for mid-trimester pregnancy termination . METHODS This r and omized trial compared misoprostol , 200 microg per vaginum q 12 h to a protocol of concentrated oxytocin plus low-dose vaginal prostagl and in E2 suppositories ( 10 mg q 6 h ) . Success was defined as an induction-to-delivery interval < or = 24 h. RESULTS Interim analysis of the first 30 ( 15-misoprostol , 15-concentrated oxytocin ) women demonstrated that the 2 groups were similar with regard to indication for delivery , gestational age , and demographic characteristics . Misoprostol was associated with a lower success rate ( 67 vs. 87 % , P = .2 ) , a longer induction-delivery interval ( 22 h vs. 18 h , P = .09 ) , a higher rate of retained placenta requiring curettage ( 27 vs. 13 % , P = .65 ) , and a higher live birth rate ( 50 vs. 0 % , P = .006 ) . CONCLUSIONS Compared to a regimen of concentrated oxytocin plus low-dose prostagl and in E2 , misoprostol administered as vaginal tablets in a dose of 200 microg q 12 h is not satisfactory for mid-trimester pregnancy termination in an unselected population OBJECTIVE Our purpose was to compare the effectiveness , women 's views of the termination procedure , and success of umbilical cord culture for vaginal and oral misoprostol versus intra-amniotic prostagl and in PGF(2alpha ) for second-trimester pregnancy termination ( STPT ) . STUDY DESIGN We r and omized 217 women , 15 to 24 weeks ' gestation , into 3 groups . Oral ( OM ) and vaginal ( VM ) misoprostol groups received 400 microg of misoprostol every 4 hours for 24 hours . The intra-amniotic PGF(2alpha ) ( IAPG ) group received 40 mg of PGF(2alpha ) followed by oxytocin infusion . Women completed self-administered question naires 3 weeks after the termination procedure . Umbilical cord sample s were collected at delivery for karyotype analysis . The primary outcome was the time from start of the procedure to placental delivery . Secondary outcomes were maternal complications , women 's acceptance of the termination procedure , and success rates of umbilical cord culture . RESULTS The time was longer for the OM group ( 30.5+/-14.4 hours ) compared with the VM group ( 18.3+/-8.2 hours ) and the IAPG group ( 21.1+/-10.2 hours ) , P<.001 for both comparisons . Women in the VM group reported being more willing to repeat the termination method in the future and reported fewer side effects than those in the other groups , P<.001 . Failure rates for umbilical cord cultures were 9.6 % , 17.0 % , and 45.6 % for the VM , OM , and IAPG groups , respectively . CONCLUSION Oral misoprostol is less effective than intra-amniotic PGF(2alpha ) or vaginal misoprostol for STPT . Women report vaginal misoprostol more acceptable than other methods . Umbilical cord culture failure rate is highest in the IAPG group A prospect i ve r and omized trial was conducted in 140 women to compare the efficacy of vaginal gemeprost with vaginal misoprostol for termination of second trimester pregnancy . Women requesting termination of second trimester pregnancy were r and omized into two groups . Group A women were given 1 mg vaginal gemeprost every 3 h for a maximum of five doses in the first 24 h , whereas group B women were given 400 micrograms vaginal misoprostol every 3 h for a maximum of five doses in 24 h. The median induction-abortion interval in the vaginal misoprostol group ( 14.1 h ) was significantly shorter than that in the gemeprost group ( 19.5 h ) . The percentage of women who achieved successful abortion within 24 h in the misoprostol group ( 80.0 % ) was significantly higher than that in the gemeprost group ( 58.6 % ) . There was no significant difference in the incidence of side effects between the two groups except for diarrhea , which was more common in the gemeprost group . The incidence of fever was more common in the misoprostol group . It is concluded that vaginal misoprostol is more effective than gemeprost in termination of second trimester pregnancy Objective To compare the effectiveness of gemeprost and misoprostol as prostagl and ins used in combination with mifepristone for induction of mid‐trimester termination Objective To compare the abortifacient efficacies of two intravaginally administered misoprostol doses and gemeprost in termination of second-trimester pregnancy . Methods Eighty-one women between 12 and 24 weeks ' gestation requesting abortion were r and omized to receive intravaginally either 100 μg of misoprostol at 6-hour intervals ( n = 27 ) , 200 μg of misoprostol at 12-hour intervals ( n = 26 ) , or 1.0 mg of gemeprost at 3-hour intervals ( n = 28 ) . The regimen was continued until abortion , or for 36 hours , with assessment of the rate of complete and incomplete abortions as well as side effects within 48 hours from the start of the treatment . Results The final rates of terminations were 74 % in the 100 μg misoprostol group , 92 % in the 200-μg misoprostol group , and 89 % in the gemeprost group . Abortion was complete in 37 % , 61 % and 32 % in each group , respectively ( P = .03 , when the 200-μg misoprostol group was compared with the two other groups ) . The inductions- to-abortion interval was longer ( P = .001 ) in he misoprostol groups ( mean 23.1 hours for the 100-μg and 27.8 hours for the 200-μg dose ) than in the gemeprost group ( 14.5 hours ) . There was less pain ( P = .01 ) , and vomiting ( P = .01 ) in the misoprostol groups that in the gemeprost group . The mean blood loss in the misoprostol groups was lower than in the gemeprost group ( P = .001 ) . Conclusion Intravaginal application of 200 μg of misoprostol at 12-hour intervals in induction of second-trimester abortion is equally effective to a st and ard gemeprost regimen . Misoprostol causes fewer side effects and is cheaper and more practical to use A prospect i ve r and omized , double-blind , controlled clinical trial to compare the clinical efficacy and side effects of intravaginal misoprostol with the traditional prostagl and in , gemeprost , in second-trimester pregnancy interruption was conducted . A sample size of 100 women was calculated to demonstrate that misoprostol was as effective as gemeprost in achieving delivery within 24 hours ( alpha = 0.1 , 80 % power ) . Women were recruited with fetal death in utero , severe fetal anomaly , or psychosocial pregnancy termination between 14 and 28 weeks gestation and r and omized to receive either 1 mg gemeprost 3 hourly for 5 doses , or 200 mcg misoprostol 6 hourly for 4 doses , intravaginally . The therapeutic regimens were repeated if undelivered by 24 hours . Those undelivered after 48 hours received an extra-amniotic PGF2 alpha infusion . The median gestation at recruitment was identical : gemeprost 19 weeks ( IQ 17 - 22 weeks ) vs. misoprostol 19 weeks ( IQ 17 - 21 weeks ) , P = 0.887 . Delivery within 24 hours occurred in 75.1 % of women receiving gemeprost and 74.9 % receiving misoprostol ( P = 1.0 ) . The median time from prostagl and in commencement to delivery was similar : gemeprost 13.7 hours ( IQ 9.0 - 23.5 hours ) vs. misoprostol 16.9 hours ( IQ 10.3 - 23.5 hours ) , P = 0.769 . A significant reduction in the incidence of vomiting in women r and omized to misoprostol occurred ( 34 % vs. 13.2 % , P = 0.017 ) . There was no significant difference in the incidence of maternal fever > 37.5 degrees C , nausea , diarrhea , or placental retention . A 200-fold pharmaceutical cost advantage was observed with the use of misoprostol compared with gemeprost . Intravaginal misoprostol performs as effectively as gemeprost in achieving delivery in the second trimester without increase in adverse effects and displaying a significant cost advantage BACKGROUND Several studies have now reported the successful use of the sublingual administration of misoprostol for medical abortion in the first trimester . The objective of this study was to assess the acceptability to women , the efficacy of the regimen , as well as the acceptability to staff of sublingual versus vaginal administration of misoprostol following mifepristone for medical abortion at 13 - 20 weeks gestation . METHODS Women were r and omized by opening consecutive sealed envelopes generated using r and om number tables . Mifepristone ( 200 mg ) was followed 36 - 48 h later by sublingual administration of misoprostol 600 microg or vaginal misoprostol 800 microg . This was followed by 3 hourly doses of misoprostol 400 microg administered sublingually or vaginally . RESULTS A total of 76 women were r and omized . Of women in the sublingual group , 24 ( 66.7 % ) expressed satisfaction with the route of misoprostol administration compared with 25 ( 62.5 % ) in the vaginal group . A higher proportion in the sublingual group used intramuscular opiates . There was no significant difference in the surgical evacuation rate between the sublingual ( three out of 36 women , 8.3 % ) and vaginal groups ( one out of 40 , 2.5 % ) , ( P=0.26 ) and acceptability to staff was the same for both methods . CONCLUSIONS Sublingual administration of misoprostol following mifepristone is an acceptable and effective alternative to vaginal administration for medical abortion at 13 - 20 weeks gestation . However , women should be advised about the greater likelihood of requiring stronger analgesia OBJECTIVE : To compare the efficacy , side effects , and complications of high-dose vaginal misoprostol with concentrated intravenous oxytocin plus low-dose vaginal prostagl and in ( PGE2 ) for second-trimester labor induction . METHODS : One hundred twenty-six consenting women with maternal or fetal indications for pregnancy termination and no prior cesarean delivery were r and omly assigned to receive either vaginal misoprostol 600 μg 1 × , 400 μg every 4 hours 5 × ( misoprostol group , n = 60 ) or escalating-dose concentrated oxytocin infusions ( 277–1,667 mU/min ) plus vaginal PGE2 10 mg every 6 hours 4 × ( oxytocin group , n = 66 ) . Both groups received concurrent extra-amniotic saline infusion for cervical ripening . Women who failed their assigned regimen received 20 mg of PGE2 suppositories every 4 hours until delivery . Analysis was by intent to treat . RESULTS : Demographic characteristics were similar between study groups . Median induction-to-delivery interval was significantly shorter in the misoprostol group ( 12 hours ) than in the oxytocin group ( 17 hours ; P < .001 ) . There was a higher induction success rate at 24 hours in the misoprostol group ( 95 % ) than in the oxytocin group ( 85 % ; P = .06 ) , although this difference did not reach statistical significance . The incidence of live birth ( 25 % versus 17 % ) , chorioamnionitis ( 5 % versus 2 % ) , and postpartum hemorrhage greater than 500 mL ( 3 % versus 3 % ) were similar between the misoprostol and oxytocin groups , respectively . Diarrhea ( 2 % versus 11 % ; P = .04 ) , nausea/emesis ( 25 % versus 42 % ; P = .04 ) , and retained placenta requiring curettage ( 2 % versus 15 % ; P = .008 ) were significantly less common in the misoprostol group when compared with the oxytocin group , respectively . Isolated intrapartum fever , however , was more frequent in the misoprostol group ( 67 % ) than in the oxytocin group ( 21 % ; P < .001 ) . CONCLUSION : Compared with concentrated oxytocin plus low-dose vaginal PGE2 , high-dose vaginal misoprostol is associated with significantly shorter induction-to-delivery intervals , fewer side effects , a lower incidence of retained placenta , and comparable incidence of live birth . LEVEL OF EVIDENCE : OBJECTIVE Our purpose was to compare the efficacy , safety , and adverse effects of intra-amniotically administered (15S)-15-methyl-prostagl and in F(2alpha ) and intravaginally administered misoprostol for second-trimester uterine evacuation . STUDY DESIGN Fifty-one patients were r and omly assigned to receive either a single 2.5-mg intra-amniotic injection of (15S)-15-methyl-prostagl and in F(2)(alpha ) ( n = 26 ) or two 200-microg intravaginal doses of misoprostol ( n = 25 ) at 12-hour intervals . The primary outcome measured was evacuation of the uterus within 24 hours . RESULTS The mean time from initiation of termination to uterine evacuation was less in the prostagl and in group than in the misoprostol group ( 17.5 + /- 8.6 hours vs 22.3 + /- 12.5 hours ) , but this was not statistically significant ( P > .05 ) . The rate of successful fetal evacuation at 24 hours was significantly higher in the prostagl and in group than in the misoprostol group ( 88 % vs 60 % , P = .02 ) . The complete-abortion rate and the incidence of adverse effects were similar in both groups . CONCLUSION The use of an intra-amniotic injection of (15S)-15-methyl-prostagl and in F(2alpha ) for midtrimester pregnancy termination is safe and is associated with a greater number of successful uterine evacuations within 24 hours , without an increase in adverse effects , than intravaginal administration of misoprostol Drugs are licensed to treat specific conditions but doctors can use them for other reasons so long as they take responsibility . This is called ‘ off-label ’ use . Sometimes the drug has not been su bmi tted to the regulatory system for the indication , other assessment has revealed that use for this indication is contraindicated . Such ‘ contraindicated ’ use is probably a greater risk than ‘ off-label ’ . Doctors use drugs off-label if they are convinced their patient can not wait for regulatory approval , there is no other available licensed drug , if they judge that the benefits outweigh the risks or sometimes just because the unlicensed drug is cheaper . The practice is common in obstetrics . In one survey of 731 birthing women , 23 % had received off-label drugs . Such prescribing is rarely controversial . Of the 10 off-label drugs in the survey , only one , the use of misoprostol for labour induction , the subject of this commentary , carries serious risks . Misoprostol ( prostagl and in E1 ) is marketed as Cytotec for the oral treatment of peptic ulcers . It has uterotonic activity but is not only unlicensed for use in pregnancy but labelled as contraindicated in pregnant women . Nevertheless , it has been used for the induction of labour since the 1990s . This off-label use is unusual , in that other related products such as dinoprostone ( prostagl and in E2 ) and oxytocin are licensed for labour induction . It was also potentially hazardous because early prescribers did not know the correct dose or the suitability of the oral formulation for vaginal use . The research they conducted to find out was relatively haphazard , and few patients were informed that they were receiving an unlicensed drug . Indirect evidence suggests that many American women have been given misoprostol for labour induction . Induction of labour was used in 18 % of births in 1998 approximately 720,000 inductions annually and in at least two large US hospitals , it was the most common agent used . It has been described in the media as ‘ the drug of choice for induction of labour ’ . It has also been widely used to induce labour in women with a previous caesarean section . In Portl and , Oregon it was used in 60 % of patients with previous caesarean deliveries who underwent induction of labour between 1996 and 1998 . Prelicensing studies normally consist of r and omised trials performed to the st and ards of the International Conference on Harmonisation Good Clinical Practice ( ICHGCP ) . This never happened with misoprostol for labour induction . Instead , doctors experimented with the dosage , either by informally ‘ trying out ’ the drug or performing small trials with idiosyncratic research protocol s , eventually accumulating sufficient data to assess efficacy . The tablets came in unscored 100 Ag and scored 200 Ag tablets , so clinicians first tried one 100 Ag tablet every 4 to 6 hours , either orally or vaginally . When uterine hyperstimulation and the occasional uterine rupture occurred , the dose was reduced by cutting the 100 Ag tablets into halves or quarters , and by 2001 , the consensus was for 25 Ag ( 1/4 tablet ) given vaginally every 4 to 6 hours . Even now some hospital pharmacies decline to cut unscored tablets due to the inherent inaccuracy of dose . Vaginal pessaries are normally formulated differently to oral tablets . They are shaped for ease of insertion and use different excipients including different binders , fillers , lubricants , disintegrants . Using an oral tablet vaginally results in a different pharmacological effect . Vaginal application of misoprostol results in slower increases and lower peak plasma concentrations than oral , but overall drug exposure is increased . With vaginal insertion , the plasma concentration remains near peak levels 4 hours after insertion . Research ers also compared misoprostol with oxytocin , with dinoprostone ( prostagl and in E2 ) gel 11–13 and dinoprostone vaginal inserts , as well as oral and vaginal use . However , no trial was of sufficient size to measure or compare reported rare but serious risks such as uterine rupture , amniotic fluid embolism or neonatal and maternal mortality . Despite the fact that off-label users may be less inclined to report adverse effects to the authorities , preliminary data suggest that misoprostol is associated with an increase in meconium staining , uterine hyperstimulation , uterine rupture , amniotic fluid embolism , maternal mortality , perinatal mortality and hypoxic ischemic encephalopathy of surviving infants . – 16,19 – 27 There are many other examples of tragedies following the widespread use of procedures or drugs before adequate scientific evaluation , such as routine prenatal X-ray pelvimetry , di-ethylstilboesterol and thalidomide during pregnancy . Small trials and lack of st and ardisation of research protocol s has made meta- analysis unreliable . The editor of this journal , commenting on a misoprostol induction trial in January 2004 wrote : ‘ Previous trials have been too small to provide clear evidence on rare but important outcomes such as uterine rupture , and even in the present larger trial there was only one uterine rupture in each group ’ . One review admits : ‘ the relative risk of rare adverse outcomes BJOG : an International Journal of Obstetrics and Gynaecology March 2005 , Vol . 112 , pp . Seventy-six consecutive patients undergoing midtrimester abortion were r and omly divided into treatment with either intracervical and ( less so ) extraamniotic prostagl and in E2 ( PGE2 ) gel or intraamniotic prostagl and in F2 alpha ( PGF2 alpha ) . At the end of 5 h the initial treatment was supplemented by an oxytocin drip and in the PGE2 group the intracervical application of gel was repeated if necessary . The second day a third application of PGE2 gel was administered to a few women . The two groups were comparable with regard to age , parity and gestational age . There was no statistical difference between the two groups in success rate during the 48 h study period ( 93 % for PGE2 versus 97 % for PGF2 alpha ) or in the average induction-to-abortion interval ( 16.8 h for PGE2 versus 16.6 h for PGF2 alpha ) . The frequency of completed abortions was statistically significantly higher and the gastrointestinal side-effects significantly lower in the PGE2-treated patients as compared to the PGF2 alpha-treated subjects . Further , there were fewer complications and the pethidine consumption in women treated with intracervical PGE2 was lower as compared to patients treated with intraamniotic PGF2 alpha . In conclusion , an intracervical PGE2 gel is found applicable and more advantageous than intraamniotic PGF2 alpha in midtrimester abortion . It is safe , convenient and equally easy to administer during the early and the later parts of the second trimester BACKGROUND To compare the efficacy and side effects of extra-amniotic prostagl and in F2alpha with intracervical misoprostol for midtrimester termination of pregnancy METHODS Forty women were r and omized to receive either intracervical misoprostol or extra-amniotic prostagl and in F2alpha for termination of pregnancy for congenital abnormalities or intrauterine fetal death . Induction-abortion interval and the incidence of side effects were analyzed for both groups . RESULTS All women in the PGF2alpha group ; aborted within 28 hours , 16 ( 80 % ) of which aborted within 20 hours . Medical termination of pregnancy was complete in 13 cases ( 65 % ) . In the misoprostol group ; all women aborted within 20 hours , 18 ( 90 % ) of which aborted within 13 hours . Medical termination of pregnancy was complete in 17 cases ( 85 % ) . The induction to abortion intervals for the extra-amniotic PGF2alpha and intracervical misoprostol were 16+/-5.9 hours , and 10.3+/-4 hours ( mean+/-s.d . ) respectively . This was statistically significant ( p=0.001 ) . The incidence of prostagl and in-associated pyrexia , vomiting and diarrhea were significantly increased in the PGF2alpha group ( p<0.05 ) . Abdominal pain was similar in both groups . There was no post-abortive hemorrhage or infection . CONCLUSIONS Misoprostol is an effective , easy to use , safe and cheap drug for termination of second trimester pregnancy . Intracervical administration of misoprostol appears to be effective and well-tolerated with less side effects and no complications . Larger , r and omized comparative studies should be carried out to assess its potential advantages Abstract . Second trimester abortion was induced in 92 women by extra‐amniotic instillation of Rivanol and /or PGF2α followed by intravenous oxytocin after 24 hours . All instillations were made via a catheter with a balloon filled with 30 ml and left in place until abortion , but never for more than 24 hours . Induction was started by Rivanol alone ( n=23 ) , PGF2α alone ( n=23 ) , Rivanol combined with PGF2α ( n=23 ) , or Rivanol combined with half dose PGF2α ( n = 23 ) and the patients were allotted to the different groups in a r and om manner . The Rivanol solution was instilled as a single dose but PGF2α was instilled every 2nd hour for 24 hours . The mean induction‐abortion time was similar in all 4 groups but a number of patients given PGF2α alone or in combination with Rivanol aborted earlier than patients induced by Rivanol alone , during the period before intravenous oxytocin was administered . Gastrointestinal side effects were equally common after Rivanol as after PGF2α . With the methods and doses used in the present investigation PGF2α alone or combined with Rivanol with subsequent oxytocin had no over‐all advantage over Rivanol The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination . Sixty women in second trimester of gestation with indications for pregnancy termination were r and omly assigned in two equal groups to receive either vaginal or oral misoprostol . The dosing regimen was 400 microg as the initial dose followed by 400 microg up to 3 doses ( 1200 microg ) if needed in each group . Efficacy and side effects were compared . The percentage of women who delivered was significantly higher in vaginal group than the oral group ( 86.7 vs. 43.3 p = 0.0006 ) . No significant differences in complication rates and induction to delivery interval were noted between the two groups . Vaginal administration of misoprostol result ed in a higher success rate for second trimester pregnancy termination , whereas , no significant differences in induction to delivery time and complication rates were noted between vaginal and oral groups Two regimens of the prostagl and in E1 analogue , gemeprost , in combination with mifepristone were compared in a r and omised trial for termination of pregnancy between 12 - 19 weeks . Thirty-six hours after treatment with 200 mg mifepristone , women were allocated at r and om to receive either 4 x 1 mg ( Group I ) or 4 x 0.5 mg ( Group II ) gemeprost by vaginal pessary every 6 hours ( n = 50 in each group ) . If abortion had not occurred after 24 h , 5 x 1 mg of gemeprost was administered every 3 h to both groups of women . Although the median abortion interval was slightly shorter in the 1 mg group ( 7.8 h vs. 8.4 h , p = 0.5 ) , the cumulative abortion rates at 24 h were similar ( 98 % vs. 96 % ) . Women in Group I required significantly more gemeprost to induce abortion than Group II ( p < 0.0001 ) . Parous women in both groups required significantly less of the prostagl and in to induce abortion . In Group II , the median abortion interval was significantly longer in primigravidae than multigravidae ( 9.5 h vs. 6.1 h ; p < 0.02 ) . There were no significant differences between the groups in the incidence of vomiting , diarrhoea or the request for analgesia . The results suggest that in parous women , the dose of gemeprost can be reduced to 0.5 mg every 6 h within the first 24 h without loss of clinical efficacy AIM To compare the effectiveness of vaginal misoprostol between dry tablet insertion and gel form for second trimester pregnancy termination . METHODS A non-blinded block r and omized controlled trial was conducted on 148 pregnant women with live fetuses in the second trimester undergoing pregnancy termination . They were r and omly allocated to receive vaginal misoprostol ( 400 microg ) either dry tablet insertion ( n=72 ) or gel form ( n=76 ) . The same dose was then repeated every 3 h if adequate uterine contraction was not achieved until 48 h after the initiation of misoprostol . If abortion did not occur within this period , the treatment was considered a failure and other technique of termination was then given based on the decision of the attending physicians and the cervical status . RESULTS The mean induction-abortion interval in group 1 ( 20.9+/-12.3 h ) was not significantly different from that in group 2 ( 17.7+/-10.2 h ) . The mean total dose of misoprostol was also not significantly different between the two groups ( group 1 , 1556.9 microg ; group 2 , 1350.9 microg ) , but the adverse effects of misoprostol ( chill and diarrhoea ) were more common in the gel group . CONCLUSION Tablet insertion or gel form of vaginal misoprostol have similar effectiveness but the gel form was associated with more common adverse effects BACKGROUND The most widely used medical method of terminating second-trimester pregnancy is the intravaginal administration of prostagl and in E2 ( dinoprostone [ PGE2 ] ) . This treatment is highly effective but is associated with severe gastrointestinal side effects and hyperpyrexia . METHODS We conducted a prospect i ve , r and omized trial comparing the efficacy and safety of misoprostol , a prostagl and in E1 analogue ( 200 micrograms intravaginally every 12 hours ) , with the efficacy and safety of PGE2 ( 20 mg intravaginally every 3 hours ) . The study population included 55 pregnant women between 12 and 22 weeks ' gestation who were undergoing termination of pregnancy for either intrauterine fetal death ( 37 women ) or medical or genetic reasons ( 18 women ) . RESULTS The rate of successful abortions within 24 hours was 81 percent ( 22 of 27 women ) with PGE2 and 89 percent ( 25 of 28 women ) with misoprostol ( P = 0.47 ) . All the women who received misoprostol had successful abortions within 38 hours . Among those who had an abortion within 24 hours , the mean interval from treatment to abortion was similar in both groups ( 10.6 hours with PGE2 and 12.0 hours with misoprostol , P = 0.33 ) . The rate of complete abortion , defined as the passage of the fetus and the placenta simultaneously , was 32 percent for PGE2 and 43 percent for misoprostol ( P = 0.56 ) . Certain side effects were more frequent in the women receiving PGE2 than in those receiving misoprostol : pyrexia ( 63 percent vs. 11 percent ; P < 0.001 ) , uterine pain ( 67 percent vs. 57 percent , P = 0.58 ) , vomiting ( 33 percent vs. 4 percent , P = 0.005 ) , and diarrhea ( 30 percent vs. 4 percent , P = 0.012 ) . The average cost per treatment was $ 315.30 for PGE2 , as compared with $ 0.97 for misoprostol . CONCLUSIONS Misoprostol is at least as effective as PGE2 for the termination of second-trimester pregnancy involving either a dead or a living fetus , but it is less costly , is easier to administer , and is associated with fewer adverse effects OBJECTIVE To compare the effectiveness of misoprostol administrated intravaginally alone versus misoprostol with oxytocin infusion for termination of pregnancy at 13 to 29 weeks . Subjects and methods . Ninety women at 13 - 29 weeks requesting pregnancy termination were r and omized to receive 200 microgram of misoprotol intravaginally every 12 hours either with oxytocin infusion or alone for up to 48 hours . RESULTS The mean induction to abortion interval was significantly shorter in the misoprostol-oxytocin group than in the misoprostol alone group ( 22+/-10.8 hours versus 27+/-14.1 hours respectively p<0.05 ) . The 48 hours successful abortion rates were 95 % and 90 % respectively . Abortion was complete in 79.1 % and 62.5 % respectively . Side effects were similar between groups . CONCLUSION Vaginal misoprostol associated with oxytocin infusion is more effective than misoprostol alone in termination of second-trimester pregnancy OBJECTIVE : To investigate the adjunctive use of mifepristone in second-trimester induction abortions using misoprostol 1 day after feticidal digoxin . METHODS : This is a r and omized , placebo-controlled , double-blind trial of mifepristone in second-trimester induction termination using misoprostol after feticidal digoxin . Women seeking abortion between 18 and 23 weeks of gestation were offered enrollment . At the time of digoxin amnioinfusion , participants received a r and omly allocated , identical-appearing capsule containing either mifepristone , 200 mg , or placebo . Patients returned the following day for induction with buccal misoprostol . The primary outcome was the time interval from the first misoprostol dose to abortion . Analysis utilized survival curves with log-rank testing . RESULTS : Of 64 women , 32 received mifepristone and 32 received placebo . The groups did not differ by ethnicity , age , parity , reason for termination , or gestational age . Median procedure time was significantly shorter for those who received mifepristone , 10 hours ( 95 % confidence interval [ CI ] 8–12 ) , than those who did not , 18 hours ( 95 % CI 15–22 ) , P<.01 , and those parous , 10 hours ( 95 % CI 9–14 ) , compared with nulliparous , 16 hours ( 95 % CI 12–22 , P=.02 ) . Other findings in the mifepristone compared with placebo group included rates of placental retention , 3.1 % compared with 6.3 % ( P=.61 ) , length of hospitalization , 0.66 days compared with 0.8 days ( P=.23 ) , and analgesic requirements , 27.2 mg compared with 39.3 mg morphine ( P=.22 ) . Side effects during induction were similar between groups . CONCLUSION : Addition of mifepristone in second-trimester termination inductions using misoprostol significantly reduces the abortion time interval . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , www . clinical trials.gov , NCT00382538 LEVEL OF EVIDENCE : Objective To examine the efficacy and side effects of concentrated oxytocin plus low-dose prostagl and in ( PG ) E2 compared with a st and ard dose of vaginal PGE2 for second-trimester pregnancy termination . Methods Patients with obstetric or fetal complications were r and omly assigned to receive either a 20-mg PGE2 vaginal suppository every 4 hours ( n = 81 ) or a concentrated oxytocin infusion plus a 10-mg PGE2 vaginal suppository every 6 hours ( n = 73 ) . Treatment success was defined as delivery ( or imminent delivery ) within 24 hours of therapy . Women who failed their assigned regimen were crossed to the alternate method . Results Indications for delivery were similar in the two groups . The success rate with oxytocin was 89 % , compared with 81 % with vaginal PGE2 ( relative risk 0.92 , 95 % confidence interval 0.8–1.04 ; P = .2 ) . Maternal fever ( P < .001 ) , nausea ( P = .02 ) , and vomiting ( P = .003 ) occurred significantly more often in women who received a 20-mg PGE2 vaginal suppository every 4 hours . Conclusion Concentrated oxytocin plus low-dose PGE2 should be considered as an alternative to vaginal PGE2 for indicated second-trimester pregnancy termination EDITORIAL COMMENT : We accepted this paper for publication because second trimester abortion is a sad necessity . The mean gestation in the series was 16 weeks and figure 4 shows the distribution of maturity at abortion . It seems proper to analyze the induction‐abortion interval , side‐effects and amount of gemeprost required and their cost . However it seems to the editorial committee that these studies should focus more on the need for surgical evacuation , immediate and late , and the presence of complications such as haemorrhage . It would be even better if follow‐up data of outcome in future pregnancies could be provided . It may not be statistically significant but it seems preferable to be in a group in which 64 % require surgical evacuation than in one in which 78 % require surgical evacuation . We require more data from a bigger series Extra-amniotic prostagl and in F2α ( PG F2α ) is probably the most widely used medical method for mid-trimester termination of pregnancy . The method is highly effective but is financially costly , particularly for poor countries faced with restricted health budgets . The aim of this study was to establish whether misoprostol administered vaginally is as effective as PG F2α . Sixty-one patients were prospect ively r and omized to receive either misoprostol ( n=30 ) vaginally , or PG F2α ( n=31 ) extra-amniotically . The overall success rate was 83.6 % . The success rates in the misoprostol and PG F2α groups were 83.3 % and 83.8 % respectively . There was no statistical difference in the groups in relation to side effects . In this carefully selected group of patients , misoprostol was as safe and effective as PG F2α in mid-trimester termination of pregnancy . In these days of financial constraints , misoprostol is the preferred method for mid-trimester termination of pregnancy OBJECTIVE To compare the effectiveness of misoprostol administered intravaginally every 6 versus every 12 hours for termination of second-trimester pregnancies . METHODS One hundred pregnant women at 12 - 22 weeks ' gestation were r and omized to receive 200 microg of misoprostol intravaginally either every 6 or every 12 hours for up to 48 hours . RESULTS The incidences of abortion within 48 hours after initial drug administration were 87.2 and 89.2 % , the complete abortion rates 43.9 and 33.3 % , and the mean abortion intervals 13.8 and 14.0 hours in the 6- and 12-hour groups , respectively . Side effects were similar between groups . CONCLUSION Misoprostol administered vaginally is effective for terminating second-trimester pregnancies . Shortening the dosing interval from 12 to 6 hours produced no significant benefit OBJECTIVE The purpose of this study was to compare the efficacy and adverse effects of vaginal misoprostol and intra-amniotic PGF2alpha for midtrimester abortion . STUDY DESIGN One hundred thirty-two women between 12 and 24 weeks ' gestation , seeking abortion in a tertiary hospital , were r and omized to receive vaginal misoprostol ( 400 microg every 3 hours ) or intra-amniotic PGF2alpha ( carboprost 1.5 mg ) . Main outcome measures were induction-to-abortion interval , success rates at 24 and 48 hours , and adverse effects . RESULTS Successful abortion rates at 24 and 48 hours between intra-amniotic PGF2alpha and vaginal misoprostol were not statistically different . However , vaginal misoprostol results in a significantly shorter mean induction-to-abortion interval , compared with intra-amniotic PGF2alpha ( misoprostol : 16.2 hours ; intra-amniotic PGF2alpha : 20.8 hours ; P = .006 ) , particularly among multiparous women ( misoprostol : 13.1 hours ; intra-amniotic PGF2alpha 18.3 hours ; P = .011 ) and for gestation below 130 days ( misoprostol : 14.6 hours ; intra-amniotic PGF2alpha : 20.2 hours ; P = .015 ) . Fever and shivering were commoner with vaginal misoprostol . CONCLUSION Vaginal misoprostol should be the regimen of choice for midtrimester abortion , particularly for multiparous women and women in the early second trimester An antiprogesterone , mifepristone ( RU486 ) , was administered to 35 patients undergoing a therapeutic interruption of pregnancy during the second and third trimester for maternal or fetal indications . A r and omized double-blind study test was performed using 150 and 450 mg of mifepristone as pretreatment prior to prostagl and ins . No toxicity or maternal morbidity were recorded . In three patients the onset of labour occurred spontaneously before prostagl and in administration . Mifepristone produced a modification in the consistency of the cervix with a statistical improvement in cervical calibration in the two groups , but the cervical effect was independent of the dose OBJECTIVE To compare the efficacy of methods for second trimester pregnancy termination . METHODS A prospect i ve r and omized study of women undergoing pregnancy termination between 14 and 28 weeks gestation . Three hundred and forty patients with poor cervical condition ( Bishop score < or = 4 ) in whom one of five termination methods were used were assessed : ( i ) extraamniotic administration of ethacridine lactate ( 82 patients ) ; ( ii ) intracervical prostagl and in ( PG ) E2 gel ( 100 patients ) ; ( iii ) intravenous infusion of concentrated oxytocin ( 36 patients ) ; ( iv ) vaginal misoprostol ( 49 patients ) ; and ( v ) balloon insertion ( 73 patients ) . Oxytocin infusion was used in all but concentrated oxytocin group to augment labor , when necessary . Patients in whom effective uterine contractions and cervical dilatation was not obtained within 48 h with the primary termination method were registered as failures . RESULTS The efficacy of each method were evaluated in terms of abortion within time . Abortion within 48 h were achieved in 98.8 % ( 81/82 ) of the patients in ethacridine group ; 97.3 % ( 35/36 ) of the patients in concentrated oxytocin group ; 90.0 % ( 90/100 ) of the patients in PGE2 group ; 97.2 % ( 71/73 ) of the patients in balloon group ; 77.5 % ( 38/49 ) of the patients in misoprostol group ( P = 0.000 , P < 0.01 , Wilcoxon ( Gehan ) statistic ) . The overall median induction-abortion interval + /- S.D. ( in h ) in each group were as follows : ethacridine lactate : 15.7 + /- 9.6 , PGE2 gel : 20.0 + /- 14.5 , concentrated oxytocin : 12.2 + /- 14.4 , misoprostol : 24.0 + /- 22.2 , balloon : 16.0 + /- 15.4 ( one way ANOVA , P = 0.003 , P < 0.01 ) . CONCLUSION In comparison with the five methods , the use of extraamniotic ethacridine , intravenous concentrated oxytocin , and balloon was found to provide more effective treatment than intracervical PGE2 and misoprostol in terms of achievement of abortion within 24 and 48 A prospect i ve r and omized double-blind placebo-controlled trial was conducted in 70 subjects to determine whether pre-treatment with misoprostol could facilitate termination of second trimester pregnancy by gemeprost . The women received either 400 micrograms oral misoprostol or placebo tablets 12 hours before the administration of vaginal pessary of gemeprost 1 mg every 3 hours . There were no significant differences in induction-abortion interval and the amount of gemeprost required between the misoprostol and the placebo group . There was no significant difference in the incidence of side effects or analgesic requirement between the two groups . We conclude that oral misoprostol is not useful in facilitating termination of second trimester pregnancy by gemeprost Objective : To determine whether the regimen for termination of second-trimester pregnancies using laminaria tents 12–24 h prior to extra-amniotic ethacridine lactate ( Rivanol ) instillation , is more effective in shortening the insertion-expulsion interval than the presently used method of abortion induction by a condom/Nelathon catheter . Design : A prospect i ve r and omised comparative study was performed at Uong Bi General Hospital in Quang Ninh Province , Vietnam , on 91 women undergoing pregnancy termination in the second trimester . Interventions : The subjects were r and omly allocated to 2 treatment groups , receiving either the Nelathon catheter-condom method ( n = 50 ) or by insertion of a laminaria tent into the cervical canal for preinduction , 13–29 h before extra-amniotic instillation of ethacridine lactate ( n = 34 ) . Seven subjects were not pretreated with the laminaria tent . Main Outcome Measures : The insertion-expulsion intervals and the incidence of side effects were assessed . Results : The mean insertion-expulsion interval in the 2 groups was not significantly different ( mean 27.5 ± 16.1 and 26.4 ± 16.4 h , respectively ) , calculating the insertion-expulsion interval from the start of active treatment , i.e. from the instillation of Rivanol or insertion of the Nelathon catheter and condom , until expulsion of the fetus . Conclusions : The laminaria-Rivanol method for pregnancy interruption is not more advantageous than the existing Nelathon catheter-condom method . Simple , successful and cost-effective methods in achieving second-trimester abortion in the Vietnamese context have therefore to be identified and tested |
13,571 | 24,414,883 | Comparison between low and high-dose trifluoperazine with placebo from a single study provided equivocal evidence of effects .
Our results agree with existing evidence that compared to placebo , trifluoperazine is an effective antipsychotic for people with schizophrenia .
Furthermore , our review provides supportive evidence that trifluoperazine increases the risk of extrapyramidal adverse effects . | BACKGROUND Trifluoperazine is a long-established high potency typical antipsychotic drug used in the treatment of schizophrenia and schizophrenia-like illnesses .
OBJECTIVES To determine absolute effects of trifluoperazine for schizophrenia and schizophrenia-like illnesses compared with placebo .
To critically appraise and summarise current evidence on the re source use , cost and economic evaluation of trifluoperazine compared with placebo for schizophrenia . | OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate A double-blind , placebo-controlled trial was carried out to determine the value of maintenance therapy with phenothiazines in a population of out patients who had recently recovered from an acute episode of schizophrenia . The drug was shown to be significantly more effective than the placebo in preventing relapse . The relationship of the trial patients to the population from which they were selected was defined in terms of clinical , historical , and social data . Maintenance therapy seems of little value in patients with a good prognosis and in the severely ill , but it is of value in the indeterminate group between these two extremes Objective To determine the cost utility of treating schizophrenic patients with olanzapine compared with other antipsychotics in a naturalistic outpatient setting . Methods The pan-European SOHO study is a 3-year , prospect i ve , outpatient , observational study of outcomes associated with antipsychotic treatment , focusing on olanzapine , in ten European countries . For the cost-utility analysis , healthcare re source use ( inpatient care , day care , outpatient psychiatric consultations and antipsychotic and concomitant medication use ) and EQ-5D data were collected at baseline and at 3 , 6 and 12 months . The perspective was that of the health service payer . UK healthcare unit costs ( year 2004 values ) were applied to the re source use data for the ten countries . UK population tariffs were applied to the EQ-5D data to determine utility values . An Epoch analysis was used to analyze the longitudinal data . Multivariate regression analyses that adjusted for baseline covariates were used to estimate the incremental cost and utility gains for patients treated with olanzapine compared with each of the other antipsychotics ( risperidone , quetiapine , amisulpride , clozapine and oral or depot typical antipsychotics ) . Results A total of 10 972 patients were enrolled at baseline , of which 9107 completed the 12-month study period . Treatment with olanzapine was more effective in terms of QALYs gained than all of the other antipsychotic treatments . Treatment with olanzapine dominated quetiapine and amisulpride . The incremental cost for olanzapine compared with risperidone was £ 226 per patient over 12 months and the incremental cost per QALY gained was £ 5156 , with bootstrap analyses showing 100 % of the replications falling below a £ 30 000 per QALY gained threshold . Compared with treatment with clozapine , olanzapine was found to be marginally more effective , at an additional cost of £ 13 per patient over 12 months and to have an incremental cost per QALY gained of £ 775 . Bootstrap analyses showed that 81 % of replications fell below a £ 30 000 per QALY gained threshold . Comparing olanzapine with oral and depot typical antipsychotics , the incremental cost was £ 849 and £ 1106 per patient over 12 months and the incremental cost per QALY gained was £ 15 696 and £ 23 331 , respectively . Bootstrap analyses showed that 98 % of the replications fell below a £ 30 000 per QALY gained threshold for the comparison with oral typical antipsychotics , and 79 % of replications for the comparison with depot preparations . Conclusions Among SOHO patients , if a funding threshold of £ 30 000 per QALY gained is assumed , this analysis suggests that olanzapine has a high probability of being the most cost-effective treatment compared with other antipsychotic treatments . However , comparison of olanzapine with clozapine and typical depot antipsychotics should be viewed with caution because clozapine is a second-line treatment and depot treatment is used for patients who do not adhere to their oral medication Because the importance of tranquilizing drugs has been difficult to assess precisely , the author undertook a study on the effect of the withdrawal of chlorpromazine and trifluoperazine on hospitalized male schizophrenics in Engl and . Although there were no major relapses among the placebo group , changes occurred that were sometimes disabling The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas BACKGROUND There are cl aims that the extra costs of atypical ( second-generation ) antipsychotic drugs over conventional ( first-generation ) drugs are offset by improved health-related quality of life . AIMS To determine the relative costs and value of treatment with conventional or atypical antipsychotics in people with schizophrenia . METHOD Cost-effectiveness acceptability analysis integrated clinical and economic r and omised controlled trial data of conventional and atypical antipsychotics in routine practice . RESULTS Conventional antipsychotics had lower costs and higher quality -adjusted life-years ( QALYs ) than atypical antipsychotics and were more than 50 % likely to be cost-effective . CONCLUSIONS The primary and sensitivity analyses indicated that conventional antipsychotics may be cost-saving and associated with a gain in QALYs compared with atypical antipsychotics The st and ard drug Stelazine ( STEL ) , at a dose of 50 mg/day , exhibited therapeutic activity significantly different from placebo ( PL ) activity on several variables , most notably BPRS , attesting to the sensitivity of the experiment . On the other h and , the investigational drug , loxapine ( LOX ) , in doses of 100 mg/day for four weeks , could be differentiated from PL as treatment in the described population on only one variable ( NGI-Imp . ) and one item of the BPRS . On several variables , positive trends were noted , but the differences from PL did not attain the critical values necessary for statistical significance at P smaller than 0.05 . One might speculate that the relatively short duration of treatment in this study might account for the difference between these disappointing results and the more gratifying results of a previous loxapine study in chronic long-term institutionalized schizophrenics with the same oral dose Twenty adult female schizophrenics were included in a double-blind , between-patient trial . Patients received either 20 mg . trifluoperazine or 150 mg . oxypertine daily in capsule form . The dose could be altered to 10 or 30 mg . trifluoperazine ( or 120 to 180 mg . oxypertine ) at the doctor 's discretion , still maintaining the double-blind discipline . The trial drugs were administered for six weeks , after a three-week period of placebo treatment . Ratings were made throughout the trial period and for four subsequent weeks , using the Wing ` A ' and Venables rating scales . Laboratory tests , including S.G.O.T. , S.P.G.T. , alkaline phosphatase , P.C.V. , E.S.R. haemoglobin , and total and differential white cell counts , were also carried out . The results of this trial do not suggest that oxypertine is superior to trifluoperazine in activating withdrawn schizophrenics . Significantly lower values for white cell count and haemoglobin were found in the oxypertine group . Side-effects , which comprised mainly vomiting , diarrhoea , dizziness and tremor , and were not clinical ly significant , were observed more frequently after administration of trifluoperazine than after oxypertine OBJECTIVES To determine the clinical and cost-effectiveness of different classes of antipsychotic drug treatment in people with schizophrenia responding inadequately to , or having unacceptable side-effects from , their current medication . DESIGN Two pragmatic , r and omised controlled trials ( RCTs ) were undertaken . The first RCT ( b and 1 ) compared the class of older , inexpensive conventional drugs with the class of new atypical drugs in people with schizophrenic disorders , whose current antipsychotic drug treatment was being changed either because of inadequate clinical response or owing to side-effects . The second RCT ( b and 2 ) compared the new ( non-clozapine ) atypical drugs with clozapine in people whose medication was being changed because of poor clinical response to two or more antipsychotic drugs . Both RCTs were four-centre trials with concealed r and omisation and three follow-up assessment s over 1 year , blind to treatment . SETTING Adult mental health setting s in Engl and . PARTICIPANTS In total , 227 participants aged 18 - 65 years ( 40 % of the planned sample ) were r and omised to b and 1 and 136 ( 98 % of the planned sample ) to b and 2 . INTERVENTIONS Participants were r and omised to a class of drug . The managing clinician selected the individual drug within that class , except for the clozapine arm in b and 2 . The new atypical drugs included risperidone , olanzapine , quetiapine and amisulpride . The conventional drugs included older drugs , including depot preparations . As in routine practice , clinicians and participants were aware of the identity of the prescribed drug , but clinicians were asked to keep their participating patient on the r and omised medication for at least the first 12 weeks . If the medication needed to be changed , the clinician was asked to prescribe another drug within the same class , if possible . MAIN OUTCOME MEASURES The primary outcome was the Quality of Life Scale ( QLS ) . Secondary clinical outcomes included symptoms [ Positive and Negative Syndrome Scale ( PANSS ) ] , side-effects and participant satisfaction . Economic outcomes were costs of health and social care and a utility measure . RESULTS Recruitment to b and 1 was less than anticipated ( 40 % ) and diminished over the trial . This appeared largely due to loss of perceived clinical equipoise ( clinicians progressively becoming more convinced of the superiority of new atypicals ) . Good follow-up rates and a higher than expected correlation between QLS score at baseline and at follow-up meant that the sample as recruited had 75 % power to detect a difference in QLS score of 5 points between the two treatment arms at 52 weeks . The recruitment to b and 2 was approximately as planned . Follow-up assessment s were completed at week 52 in 81 % of b and 1 and 87 % of b and 2 participants . B and 1 data showed that , on the QLS and symptom measures , those participants in the conventional arm tended towards greater improvements . This suggests that the failure to find the predicted advantage for new atypicals was not due to inadequate recruitment and statistical power in this sample . Participants reported no clear preference for either class of drug . There were no statistically significant differential outcomes for participants entering b and 1 for reasons of treatment intolerance to those entering because of broadly defined treatment resistance . Net costs over the year varied widely , with a mean of 18,850 pounds sterling in the conventional drug group and 20,123 pounds sterling in the new atypical group , not a statistically significant difference . Of these costs , 2.1 % and 3.8 % were due to antipsychotic drug costs in the conventional and atypical group , respectively . There was a trend towards participants in the conventional drug group scoring more highly on the utility measure at 1 year . The results for b and 2 showed an advantage for commencing clozapine in quality of life ( QLS ) at trend level ( p = 0.08 ) and in symptoms ( PANSS ) , which was statistically significant ( p = 0.01 ) , at 1 year . Clozapine showed approximately a 5-point advantage on PANSS total score and a trend towards having fewer total extrapyramidal side-effects . Participants reported at 12 weeks that their mental health was significantly better with clozapine than with new atypicals ( p < 0.05 ) . Net costs of care varied widely , but were higher than in b and 1 , with a mean of 33,800 pounds sterling in the clozapine group and 28,400 pounds sterling in the new atypical group . Of these costs , 4.0 % and 3.3 % , respectively , were due to antipsychotic drug costs . The increased costs in the clozapine group appeared to reflect the licensing requirement for inpatient admission for commencing the drug . There was a trend towards higher mean participant utility scores in the clozapine group . CONCLUSIONS For b and 1 , there is no disadvantage in terms of quality of life and symptoms , or associated costs of care , over 1 year in commencing conventional antipsychotic drugs rather than new atypical drugs . Conventional drugs were associated with non-significantly better outcomes and lower costs . Drug costs represented a small proportion of the overall costs of care ( < 5 % ) . For b and 2 , there is a statistically significant advantage in terms of symptoms but not quality of life over 1 year in commencing clozapine rather than new atypical drugs , but with increased associated costs of care . The results suggest that conventional antipsychotic drugs , which are substantially cheaper , still have a place in the treatment of patients unresponsive to , or intolerant of , current medication . Further analyses of this data set are planned and further research is recommended into areas such as current antipsychotic treatment guidance , valid measures of utility in serious mental illness , low-dose ' conventional ' treatment in first episode schizophrenia , QLS validity and determinants of QLS score in schizophrenia , and into the possible financial and other mechanisms of rewarding clinician participation in trials This collaborative study on the efficacy of high doses of trifluoperazine in chronic schizophrenia showed that treatment response was related to length of hospitalization ; short-term patients benefited most . High doses of trifluoperazine were most effective with those short-term patients who had been on a piperazine phenothiazine prior to the study . Also , most placebo patients who had been receiving low doses of phenothiazines before the study did not suffer deleterious effects while they were off medication . Treatment implication s are discussed The hypothesis is advanced that any population of patients can be divided into those with a good prognosis , a poor prognosis , and an intermediate prognosis in respect to a particular treatment . The outcome of a clinical trial of treatment will be partly determined by the proportion of patients selected for the trial from each of these prognostic groups . The implication s of the hypothesis are illustrated by consideration of three recent trials of treatment for psychiatric patients BACKGROUND In two recent r and omised clinical trials , a meta- analysis and in an effectiveness study analysing routine data from the U.S. Veterans Administration the superiority of the newer atypical drugs over typical antipsychotic drugs , concerning both their efficacy and their side-effect profile , has been question ed . AIMS OF THE STUDY To analyse the effectiveness and cost of atypical versus typical antipsychotic treatment for schizophrenia in routine care . METHODS Cohort study using routine care data from a statutory sickness fund with 5.4 million insured in Germany . To be included , patients had to be discharged with a diagnosis of schizophrenia in 2003 and fulfil membership criteria . Main outcome measures were rehospitalisation rates , mean hospital bed days , mean length of stay , cost of inpatient and pharmaceutical care to the sickness fund during follow-up and medication used to treat side-effects . RESULTS 3121 patients were included into the study . There were no statistically significant differences in the effectiveness of atypical and typical antipsychotics on rehospitalisation during follow-up ( rehospitalisation rate ratio 1.07 , 95 % confidence interval 0.86 to 1.33 ) . However , there were consistent observations of atypical antipsychotics being more effective for severe cases of schizophrenia ( 14.6 % of study population ; > 61 prior bed days per year in 2000 - 2002 ) in the follow-up period , whereas for the other severity strata typical antipsychotics seemed more effective in reducing various rehospitalisation outcomes . Patients treated with atypical antipsychotics received significantly less prescriptions for anticholinergics or tiaprid ( relative risk 0.26 , 95 % confidence interval 0.18 to 0.38 ) . DISCUSSION The effectiveness of atypical antipsychotics for schizophrenia on rehospitalisation measures appeared similar to that of typical antipsychotics . With the exception of severe cases , the higher costs for atypical antipsychotics were not offset by savings from reduced inpatient care . Major limitations include the lack of statistical power for subgroup analyses , the lack of clinical severity scale data and of life-course medical history data which both increase the risk of residual confounding by disease severity . CONCLUSIONS This study provides evidence that the effectiveness of atypical and typical antipsychotics measured in terms of hospital readmissions appears to be similar in routine care . IMPLICATION S FOR HEALTH CARE PROVISION AND USE From a clinical perspective , this study provides evidence that the effectiveness of atypical and typical antipsychotics measured in terms of hospital readmissions appears to be similar in routine care . IMPLICATION S FOR HEALTH POLICIES Routine data studies can yield valuable information for policy decision-makers on the costs and the effectiveness of pharmaceuticals in routine care , complementing efficacy data from r and omised clinical trials currently used for licensing and reimbursement decisions . IMPLICATION S FOR FURTHER RESEARCH The non-significant differences in the effectiveness of atypical compared to typical antipsychotics according to severity of disease should be investigated in a prospect i ve observational study or in a r and omised clinical trial BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials This pilot study was conducted to compare both the clinical effectiveness and the treatment costs of newer ( atypical ) antipsychotic medications ( clozapine and risperidone ) with those of older ( classic ) neuroleptic medications ( chlorpromazine and haloperidol ) for psychosis in a community mental health care setting . The study used a retrospective , uncontrolled , open , nonr and omized , within-subjects design and relied on medical records as a data source for 37 clients . All clients received older antipsychotics for at least 1 year , newer antipsychotics for a transition period of 3 months , and the newer agents for at least an additional year . The newer antipsychotic medications were more effective and less costly ( total cost of care , $ 3000 less per client per year [ 1997 dollars ] ) than the older medications . Effect-size estimates for the measured variables provide a guide for future research into the cost-effectiveness of these newer medications within the community mental health care setting . These findings can provide policy makers with guidance on treating people with major mental disorders in the most effective and efficient manner . Because of limited budgets , community mental health centers making the investment in newer , more expensive medications to improve client outcomes have to maintain the same or lower total cost of care . Results of the current study suggest that short-term investment in the newer medications by community mental health centers offers superior clinical effectiveness and lower long-term overall cost of care |
13,572 | 28,095,780 | No effect of medication review was found on clinical outcomes ( mortality , hospital admissions/healthcare use , the number of patients falling , physical and cognitive functioning ) , except a decrease in the number of falls per patient .
Furthermore no effect was found on quality of life and evidence was inconclusive about the effect on economical outcome measures .
However , an effect was found on most drug-related problems : medication review result ed in a decrease in the number of drug-related problems , more changes in medication , more drugs with dosage decrease and a greater decrease or smaller increase of the number of drugs .
Conclusions An isolated medication review during a short term intervention period has an effect on most drug-related outcomes , minimal effect on clinical outcomes and no effect on quality of life .
No conclusion can be drawn about the effect on economical outcome measures . | Background Medication review is often recommended to optimize medication use .
In clinical practice it is mostly operationalized as an intervention without co- interventions during a short term intervention period .
However , most systematic review s also included co- interventions and prolonged medication optimization interventions .
Furthermore , most systematic review s focused on specific patient groups ( e.g. polypharmacy , elderly , hospitalized ) and /or on specific outcome measures ( e.g. hospital admissions and mortality ) .
Therefore , the objective of this study is to assess the effectiveness of medication review as an isolated short-term intervention , irrespective of the patient population and the outcome measures used . | CONTEXT Criteria for potentially inappropriate medication use among elderly patients have been used in the past decade in large US epidemiological surveys to identify population s at risk and specifically target risk-management strategies . In contrast , in Europe little information is available about potentially inappropriate medication use and is based on small studies with uncertain generalizability . OBJECTIVE To estimate the prevalence and associated factors of potentially inappropriate medication use among elderly home care patients in European countries . DESIGN , SETTING , AND PARTICIPANTS Retrospective cross-sectional study of 2707 elderly patients receiving home care ( mean [ SD ] age , 82.2 [ 7.2 ] years ) representatively enrolled in metropolitan areas of the Czech Republic , Denmark , Finl and , Icel and , Italy , the Netherl and s , Norway , and the United Kingdom . Patients were prospect ively assessed between September 2001 and January 2002 using the Minimum Data Set in Home Care instrument . MAIN OUTCOME MEASURES Prevalence of potentially inappropriate medication use was documented using all expert panels criteria for community-living elderly persons ( Beers and McLeod ) . Patient-related characteristics independently associated with inappropriate medication use were identified with a multiple logistic regression model . RESULTS Combining all 3 sets of criteria , we found that 19.8 % of patients in the total sample used at least 1 inappropriate medication ; using older 1997 criteria it was 9.8 % to 10.9 % . Substantial differences were documented between Eastern Europe ( 41.1 % in the Czech Republic ) and Western Europe ( mean 15.8 % , ranging from 5.8 % in Denmark to 26.5 % in Italy ) . Potentially inappropriate medication use was associated with patient 's poor economic situation ( adjusted relative risk [ RR ] , 1.96 ; 95 % confidence interval [ CI ] , 1.58 - 2.36 ) , polypharmacy ( RR , 1.91 ; 95 % CI , 1.62- 2.22 ) , anxiolytic drug use ( RR , 1.82 ; 95 % CI , 1.51 - 2.15 ) , and depression ( RR , 1.29 ; 95 % CI , 1.06 - 1.55 ) . Negatively associated factors were age 85 years and older ( RR , 0.78 ; 95 % CI , 0.65 - 0.92 ) and living alone ( RR , 0.76 ; 95 % CI , 0.64 - 0.89 ) . The odds of potentially inappropriate medication use significantly increased with the number of associated factors ( P<.001 ) . CONCLUSIONS Substantial differences in potentially inappropriate medication use exist between European countries and might be a consequence of different regulatory measures , clinical practice s , or inequalities in socioeconomic background . Since financial re sources and selected patient-related characteristics are associated with such prescribing , specific educational strategies and regulations should reflect these factors to improve prescribing quality in elderly individuals in Europe ZusammenfassungZIELE DER STUDIE : 1 . Bestimmung der Prävalenz von Polypharmakotherapie und unangemessenem Arzneimittelgebrauch bei älteren internistischen Patienten in Österreich ; 2 . Einschätzung deren Bedeutung für das Auftreten von unerwünschten Arzneimittelwirkungen ; 3 . Suche nach Prädiktoren für das Auftreten von unerwünschten Arzneimittelwirkungen bei einer älteren Patienten population . METHOD IK : In einer monozentrischen Kohortenstudie wurden über 3 Monate alle neu aufgenommenen Patienten ≥ 75 Jahren eingeschlossen . Die Aufnahmemedikation wurde durch ein multidisziplinäres Team bestehend aus Krankenhausapothekern und Internisten auf ihre angemessene Anwendung hin analysiert und überprüft , ob eine unerwünschte Arzneimittelwirkung aufgetreten war . ERGEBNISSE : Es wurden insgesamt 543 Patienten analysiert ( Altersmedian 82 Jahre , 60,2 % Frauen ) . Die mittlere Medikamentenanzahl bei Aufnahme betrug 7,5 ± 3,8 . Frauen nahmen signifikant mehr Medikamente ein als Männer ( 7,8 vs. 6,8 , p = 0,013 ) . 58,4 % der Patienten erfüllten das gewählte Kriterium für Polypharmakotherapie ( > 6 Medikamente ) . Folgende Faktoren waren mit Polypharmakotherapie assoziiert : weibliches Geschlecht , Pflegebedürftigkeit , hohe Anzahl an Entlassungsdiagnosen und ein hoher Punktwert auf der Charlson Komorbiditäts-Skala . Verzichtbare Medikamente wurden bei 36,3 % aller Patienten gefunden , Medikamente , die für alte Menschen inadäquat sind , bei 30,1 % , Doppelverordnungen bei 7,6 % , Fehldosierungen bei 23,4 % und potenzielle Medikamenteninteraktionen bei 65,8 % . Unerwünschte Arzneimittelwirkungen wurden bei 97/543 Patienten gefunden ( 17,8 % ) . In 56,7 % der Fälle war die unerwünschte Arzneimittelwirkung Grund für die stationäre Aufnahme und bei 18,7 % war eine Arzneimittelinteraktion sehr wahrscheinlich an der Entstehung beteiligt . Risikofaktoren für unerwünschte Arzneimittelwirkungen waren weibliches Geschlecht , Polymorbidität , Niereninsuffizienz und unangemessener Arzneimittelverordnung . SCHLUSSFOLGERUNG : Polypharmakotherapie , unangemessene Verschreibung und unerwünschte Arzneimittelwirkungen sind bei älteren internistischen Patienten in dem untersuchten österreichischen Zentrum vergleichbar häufig wie in and eren westlichen Ländern . Zur Verbesserung der Arzneimittelsicherheit bei dieser Hochrisikogruppe erscheint uns eine bessere Verschreibungsqualität bedeutsamer als eine Verminderung der Medikamentenanzahl . Summary OBJECTIVE : The aim of the study was to assess the prevalence of polypharmacy and inappropriate drug use in elderly internal-medicine patients in one Austrian center and to define the impact of these and other identified predictors on the occurrence of adverse drug events . METHODS : All patients ≥ 75 years admitted to selected internal wards of a university hospital were included in a monocentric prospect i ve cohort study over a period of three months . The pre-admission medication of the patients was analyzed with respect to appropriateness by a multidisciplinary team consisting of pharmacists and physicians trained in internal medicine . The medication was evaluated for the occurrence of adverse drug events . RESULTS : A total of 543 patients were analyzed ( median age 82 years ; 60.2 % female ) . The mean number of drugs taken was 7.5 ± 3.8 , with women taking significantly more drugs than men ( 7.8 vs. 6.8 , P = 0.013 ) . Overall , 58.4 % of the patients fulfilled the given criteria for polypharmacy ( > 6 drugs ) . The following factors were associated with polypharmacy : female sex , need for nursing care , high number of discharge diagnoses and high Charlson comorbidity score . Unnecessary drugs were found prescribed in 36.3 % of all patients , drugs to avoid ( Beers criteria ) in 30.1 % , duplication in 7.6 % , wrong dosage in 23.4 % and possible drug-drug interactions in 65.8 % . Adverse drug events were identified in 17.8 % of the patients ( 97/543 ) , among whom the adverse drug event was the reason for hospital admission in 56.7 % of the cases and a drug-drug interaction was involved in 18.7 % . Risk factors for adverse drug events were female sex , polymorbidity , renal dysfunction and inappropriate prescribing . CONCLUSION : Polypharmacy , inappropriate prescribing and adverse drug events were highly prevalent in a cohort of elderly internal-medicine patients in Austria . To improve drug safety in this high-risk population , appropriate prescribing might be more important than simply reducing the number of prescribed drugs OBJECTIVES To determine whether a medication review by a specialized team would promote regimen changes in elders taking multiple medications and to measure the effect of regimen changes on monthly cost and functioning . DESIGN A r and omized-controlled trial . SETTING Health center ambulatory clinic . PARTICIPANTS Community-dwelling older adults taking five or more medications were assessed at baseline and 6 weeks . A medication-change intervention group of 57 elders was compared with a control group of 76 elder adults . INTERVENTION The primary intervention was a comprehensive review and recommended modification of a patient 's medication regimen . Changes were endorsed by each patient 's primary physician and discussed with each patient . MEASUREMENTS Measures were the Timed Manual Performance Test , Physical Performance Test , Functional Reach Assessment , subtests from the Wechsler Adult Intelligence Scale , a modified R and t Memory Test , the Center for Epidemiological Studies -Depression Scale , the Self-Rating Anxiety Scale , and the R and 36-item Health Survey 1.0 . Comorbidity was determined using the International Classification of Diseases , Ninth Revision , Clinical Modification . Medication usage was determined using brown bag review . RESULTS Intervention subjects decreased their medications by an average of 1.5 drugs . No differences in functioning were observed between groups . Intervention subjects saved an average $ 26.92 per month in wholesale medication costs ; control subjects saved $ 6.75 per month ( P<.006 ) . CONCLUSION Although the intervention significantly reduced the medications taken and monthly cost , most patients were resistant to reducing medications to the recommended level . Further study is needed to underst and patient resistance to reducing adverse polypharmacy and to devise better strategies for addressing this important problem in geriatric health . Greater focus on prescriber behavior is recommended OBJECTIVES to evaluate specialist geriatric input and medication review in patients in high-dependency continuing care . DESIGN prospect i ve , r and omised , controlled trial . SETTING two residential continuing care hospitals . PARTICIPANTS two hundred and twenty-five permanent patients . INTERVENTION patients were r and omised to either specialist geriatric input or regular input . The specialist group had a medical assessment by a geriatrician and medication review by a multidisciplinary expert panel . Regular input consisted of review as required by a medical officer attached to each ward . Re assessment occurred after 6 months . RESULTS one hundred and ten patients were r and omised to specialist input and 115 to regular input . These were comparable for age , gender , dependency levels and cognition . After 6 months , the total number of medications per patient per day fell from 11.64 to 11.09 in the specialist group ( P = 0.0364 ) and increased from 11.07 to 11.5 in the regular group ( P = 0.094 ) . There was no significant difference in mortality or frequency of acute hospital transfers ( 11 versus 6 in the specialist versus regular group , P = 0.213 ) . CONCLUSION specialist geriatric assessment and medication review in hospital continuing care result ed in a reduction in medication use , but at a significant cost . No benefits in hard clinical outcomes were demonstrated . However , qualitative benefits and lower costs may become evident over longer periods OBJECTIVE : To investigate actual cost and adverse effect outcomes associated with a pharmacotherapy consultation in ambulatory care patients receiving polypharmacy . METHODS : Patients receiving five or more chronic medications were r and omized to receive pharmacotherapy consultation or usual medical care . Outcomes measured were changes in drug costs , medical costs , and drug-related symptoms six months after the consultation . Data were analyzed with unpaired Student 's t-test for continuous data . χ2 Analysis was used for categorical data . Patients and physicians were surveyed about their perceptions of the consultations after the study period . RESULTS : Drug and medical costs did not differ before and after the consultation . More patients in the consultation group had adverse symptom scores improve by two or more points , and fewer had symptom scores worsen by two or more points than in the control group . Seventy percent of patients and 76 % of physicians believed that the consult was beneficial . CONCLUSIONS : Polypharmacy patients are the most likely to have drug-related problems and require intervention . Of all the interventions performed in this study , 73 % of the original problems were recognized only through a patient interview , suggesting that an interpersonal relationship remains critical to the provision of pharmaceutical care . Although patients and physicians see intuitive value in pharmaceutical care , pharmacists need to exert more energy in the direction of marketing the profession . Finally , there are numerous difficulties in measuring the benefits of these interventions , possibly making broad-based interventions in complicated patients too difficult to assess accurately . Future studies should focus on patients with limited , specific problems or on interventions with narrow goals Background Polypharmacy in the Swedish elderly population is currently a prioritised area of research with a focus on reducing the use of potentially inappropriate medications ( PIMs ) . Multi-professional interventions have previously been tested for their ability to improve drug therapy in frail elderly patients . Objective This study aim ed to assess a structured model for pharmacist-led medication review s in primary health care in southern Sweden and to measure its effects on numbers of patients with PIMs ( using the definition of the Swedish National Board of Health and Welfare ) using ≥10 drugs and using ≥3 psychotropics . Methods This study was a r and omised controlled clinical trial performed in a group of patients aged ≥75 years and living in nursing homes or the community and receiving municipal health care . Medication review s were performed by trained clinical pharmacists based on nurse-initiated symptom assessment s with team-based or distance feedback to the physician . Data were collected from the patients ’ electronic medication lists and medical records at baseline and 2 months after the medication review . Results A total of 369 patients were included : 182 in the intervention group and 187 in the control group . One-third of the patients in both groups had at least one PIM at baseline . Two months after the medication review s , the number of intervention group patients with at least one PIM and the number of intervention group patients using ten or more drugs had decreased ( p = 0.007 and p = 0.001 , respectively ) , while there were no statistically significant changes in the control patients . No changes were seen in the number of patients using three or more psychotropic drugs , although the dosages of these drugs tended to decrease . Drug-related problems ( DRPs ) were identified in 93 % of the 182 patients in the intervention group . In total , there were 431 DRPs in the intervention group ( a mean of 2.5 DRPs per patient , range 0–9 , SD 1.5 at 95 % CI ) and 16 % of the DRPs were related to PIMs . Conclusions Medication review s involving pharmacists in primary health care appear to be a feasible method to reduce the number of patients with PIMs , thus improving the quality of pharmacotherapy in elderly patients BACKGROUND regular medication review has been recommended for those over 75 and those on multiple drug therapy . Pharmacists are a potential source of assistance in review ing medication . Evidence of the benefits of this process is needed . OBJECTIVE to study the effect of medication review led by a pharmacist on resolution of pharmaceutical care issues , medicine costs , use of health and social services and health-related quality of life . DESIGN r and omized , controlled trial . SETTING general medical practice s in the Grampian region of Scotl and . SUBJECTS patients aged at least 65 years , with at least two chronic disease states who were taking at least four prescribed medicines regularly . METHODS pharmacists review ed the drug therapy of 332 patients , using information obtained from the practice computer , medical records and patient interviews . In 168 patients , a pharmaceutical care plan was then drawn up and implemented . The 164 control patients continued to receive normal care . All outcome measures were assessed at baseline and after 3 months . RESULTS all patients had at least two pharmaceutical care issues at baseline . Half of these were identified from the prescription record , the rest from notes and patient interview . Of all the issues , 21 % were resolved by information found in notes and 8.5 % by patient interview . General practitioners agreed with 96 % of all care issues documented on the care plans in the intervention group . At the time of follow-up , 70 % of the remaining care issues had been resolved in the intervention group , while only 14 % had been resolved in the control group . There were no changes in medicine costs or health-related quality of life in either group . There were small increases in contacts with health-care professionals and slightly fewer hospital admissions among the intervention group than the control group . CONCLUSIONS pharmacist-led medication review has the capacity to identify and resolve pharmaceutical care issues and may have some impact on the use of other health services Abstract Objective . To determine whether a pharmacist-led medications review in primary care reduces the number of drugs and the number of drug-related problems . Design . Prospect i ve r and omized controlled trial . Setting . Liljeholmen Primary Care Centre , Stockholm , Sweden . Subjects . 209 patients aged ≥ 65 years with five or more different medications . Intervention . Patients answered a question naire regarding medications . The pharmacist review ed all medications ( prescription , non-prescription , and herbal ) regarding recommendations and renal impairment , giving advice to patients and GPs . Each patient met the pharmacist before seeing their GP . Control patients received their usual care . Main outcome measures . Drug-related problems and number of drugs . Secondary outcomes included health care utilization and self-rated health during 12 months of follow-up . Results . No significant difference was seen when comparing change in drug-related problems between the groups . However , a significant decrease in drug-related problems was observed in the intervention group ( from 1.73 per patient at baseline to 1.31 at follow-up , p < 0.05 ) . The change in number of drugs was more pronounced in the intervention group ( p < 0.046 ) . Intervention group patients were not admitted to hospital on fewer occasions or for fewer days , and there was no significant difference between the two groups regarding utilization of primary care during follow-up . Self-rated health remained unchanged in the intervention group , whereas a drop ( p < 0.02 ) was reported in the control group . This result ed in a significant difference in change in self-rated health between the groups ( p < 0.047 ) . Conclusions . The addition of a skilled pharmacist to the primary care team may contribute to reductions in numbers of drugs and maintenance of self-rated health in elderly patients with polypharmacy Objective To describe the scenario and frequency of drug-related problems ( DRPs ) in in- patients and to determine whether a pharmacotherapeutic advisory intervention aim ing at reducing DRPs could affect rates of re-hospitalisation and /or death within 6 months . Methods This prospect i ve , r and omised , controlled advisory intervention study was carried out at the Clinic of Internal Medicine at Stockholm Söder Hospital . Three hundred patients from four wards took part in the study . Patients taking two drugs or more were included . In the intervention arm , potential drug interactions were found using a computer system . Medical symptoms were estimated by a nurse together with the patient . Creatinine clearance was calculated . Thereafter a clinical pharmacologist scrutinised the patient´s medical record for DRPs together with the nurse . DRPs judged to be clinical ly relevant result ed in written advice to the physician in charge of the patient . The control group received usual care . Results In the intervention group , a total of 299 DRPs were found among 71 % of the patients ( 106/150 ) . The number of written letters of advice to the physicians in charge was 106 . Of these , 63 % were accepted . After 6 months , the proportion of re-hospitalisations or death in the intervention group was 49 % ( 73/150 ) compared to 46 % ( 69/150 ) in the control group . The difference was not significant . Conclusions DRPs were common . Potential drug interactions and adverse drug reactions dominated . Hospital-based medication review by a clinical pharmacologist was not associated with reduced rates of re-hospitalisation and /or death . The clinical relevancy of DRPs might be overestimated as a risk for re-hospitalisation or death . It is of great importance to clarify if and how drug-related problems can be prevented . In design ing such studies , one should consider choosing inclusion criteria that accumulate risk BACKGROUND Pharmacists can improve patient outcomes in institutional and pharmacy setting s , but little is known about their effectiveness as consultants to primary care physicians . We examined whether an intervention by a specially trained pharmacist could reduce the number of daily medication units taken by elderly patients , as well as costs and health care use . METHODS We conducted a r and omized controlled trial in family practice s in 24 sites in Ontario . We r and omly allocated 48 r and omly selected family physicians ( 69.6 % participation rate ) to the intervention or the control arm , along with 889 ( 69.5 % participation rate ) of their r and omly selected community-dwelling , elderly patients who were taking 5 or more medications daily . In the intervention group , pharmacists conducted face-to-face medication review s with the patients and then gave written recommendations to the physicians to resolve any drug-related problems . Process outcomes included the number of drug-related problems identified among the senior citizens in the intervention arm and the proportion of recommendations implemented by the physicians . RESULTS After 5 months , seniors in the intervention and control groups were taking a mean of 12.4 and 12.2 medication units per day respectively ( p = 0.50 ) . There were no statistically significant differences in health care use or costs between groups . A mean of 2.5 drug-related problems per senior was identified in the intervention arm . Physicians implemented or attempted to implement 72.3 % ( 790/1093 ) of the recommendations . INTERPRETATION The intervention did not have a significant effect on patient outcomes . However , physicians were receptive to the recommendations to resolve drug-related problems , suggesting that collaboration between physicians and pharmacists is feasible OBJECTIVE To investigate the effectiveness of an educational Quality Use of Medicines program , delivered at the level of general practice , on medicines use , falls and quality of life in people aged > or = 65 years . DESIGN Cluster r and omised controlled trial conducted in 2002 . SETTING General practice s in the Hunter Region , New South Wales , Australia . PARTICIPANTS Twenty general practitioners recruited 849 patients to participate in the study . INTERVENTION Education ( academic detailing , provision of prescribing information and feedback ) ; medication risk assessment ; facilitation of medication review ; financial incentives . MAIN OUTCOME MEASURES PRIMARY MEASURES a composite score reflecting use of benzodiazepines , non-steroidal anti-inflammatory drugs ( NSAIDs ) and thiazide diuretics ; secondary measures : use of medication review s , occurrence of falls , quality of life ( as assessed by SF-12 and EQ-5D survey scores . RESULTS Compared with the control group , participants in the intervention group had increased odds of having an improved medication use composite score ( odds ratio [ OR ] , 1.86 ; 95 % CI , 1.21 - 2.85 ) at 4-month follow-up but not at 12 months . At 4-month follow-up , the intervention group had reduced odds of using NSAIDs ( OR , 0.62 ; 95 % CI , 0.39 - 0.99 ) and showed a non-significant reduction in use of benzodiazepines ( OR , 0.51 ; 95 % CI , 0.20 - 1.30 ) and thiazide diuretics ( OR , 0.70 ; 95 % CI , 0.48 - 1.01 ) . Changes in drug use were not significant at 12-month follow-up . At 12 months , intervention-group participants had lower adjusted ORs ( AORs ) for having a fall ( AOR , 0.61 ; 95 % CI , 0.41 - 0.91 ) , injury ( AOR , 0.56 ; 95 % CI , 0.32 - 0.96 ) , and injury requiring medical attention ( AOR , 0.46 ; 95 % CI , 0.30 - 0.70 ) . Quality -of-life scores were unaffected by the intervention . CONCLUSION Education and systems for medication review conducted by GPs can be used to improve use of medicines . These interventions are associated with a reduction in falls among older people , without adverse effects on quality of life Purpose The feasibility of applying the Fit fOR The Aged ( FORTA ) list , a drug classification combining positive and negative labeling of drugs , should be studied in geriatric patients and medication quality and clinical endpoints measured . FORTA labels range from A ( indispensable ) , B ( beneficial ) , C ( question able ) to D ( avoid ) . Methods A prospect i ve r and omized controlled pilot trial was performed in hospitalized geriatric patients in whom the FORTA instrument or st and ard care was applied . Patients were r and omly admitted to an intervention and a control ward . Changes of FORTA label distributions between admission and discharge , over- and under-prescription rates , clinical endpoints including the number of falls during the hospitalization , and Barthel Index ( BI ) at admission and discharge were measured . Results Polypharmacy persisted in both groups . At discharge , a higher rate of A drugs was prescribed in the intervention group ( 58 patients , median age 84 years ) vs. st and ard care ( 56 patients , median age 83 years , p < 0.02 ) , and both over- and under-prescriptions were significantly lower in the FORTA than in the control group ( p < 0.03 ) . Two ( 3.4 % ) intervention , but 12 ( 21.4 % ) control , patients fell at least once ( p < 0.001 ) . The fall rate per 1,000 patient years was 1.5 ± 8.3 in the intervention and 10.6 ± 25.4 in the control group ( p < 0.004 ) . Conclusions This pilot study shows that the application of the FORTA list is feasible in geriatric patients . In this small study , the medication quality improved in the intervention group , but polypharmacy persisted in both groups . The fall rate was significantly lower in the intervention group . These encouraging results must be interpreted carefully Background and objective Potentially inappropriate medication use is a major safety issue in the elderly and may cause a substantial proportion of drug-related hospital admissions . Hospitalisation could result in a change in the quantity and type of drugs , but its effect on potentially inappropriate drug use is still unknown . The aim of this study was to estimate the potentially inappropriate medication prevalence in patients ≥70 years of age at admission to and at discharge from an acute medical geriatric unit , and to identify the factors associated with no longer being a potentially inappropriate drug user at hospital discharge . Methods A prospect i ve drug surveillance study was undertaken in 2018 elderly patients ( ≥70 years of age ) admitted to an acute medical geriatric unit in Limoges University Hospital , France . Prescribing patterns were established at admission and at discharge . Potentially inappropriate medication use was evaluated according to a list derived from the Beers criteria and adapted to French practice . “ To be no longer a potentially inappropriate drug user at discharge ” was defined as using at least one potentially inappropriate medication at admission and not using it at discharge . Results The numbers of drugs used at admission/discharge were 6.2 ± 3.1/5.4 ± 2.5 . The prevalence of potentially inappropriate medication use decreased from 66 % ( 95 % CI 63.8 , 68.0 ) at admission to 43.6 % ( 95 % CI 41.3 , 45.9 ) at discharge . At discharge , 535 subjects were no longer potentially inappropriate medication users . Multivariate analysis showed that no longer being a potentially inappropriate medication user was associated with the number of drugs used ( 4–6 drugs vs ≤3 odds ratio [ OR ] 1.20 ; 95 % CI 0.86 , 1.68 ; 7–9 drugs vs ≤3 OR 1.37 ; 95 % CI 0.97 , 1.93 ; ≥10 drugs vs ≤3 OR 1.64 ; 95 % CI 1.10 , 2.44 ) , age ( 80–89 years vs 70–79 years OR 1.38 ; 95 % CI 1.03 , 1.85 ; ≥90 years vs 70–79 years OR 1.69 ; 95 % CI 1.22 , 2.83 ) , cerebral vasodilator use ( OR 2.87 ; 95 % CI 2.31 , 3.57 ) , analgesic use ( OR 1.54 ; 95 % CI 1.06 , 2.25 ) and concomitant use of psychotropic drugs of the same therapeutic class ( OR 1.94 ; 95 % CI 1.29 , 2.92 ) . Conclusion Hospitalisation in geriatric services results in a reduction in potentially inappropriate medication use . Improved pharmacological education of practitioners , especially with regard to drug adverse effects , is desirable to improve management of geriatric patients Objective We investigated the health-related effect of systematic medication review performed by a clinical pharmacist and a clinical pharmacologist on nonelective elderly orthopedic patients . Methods This is a nonblinded r and omized controlled study of 108 patients 65 years or older treated with at least 4 drugs . For the intervention , the clinical pharmacist review ed the participants ' medication after completion of the usual medication routine . Information was collected from medical charts , interviews with participants , and data base registration s of drug purchase . Results were conferred with the clinical pharmacologist , and recommendations were delivered directly to the ward physicians . The control was usual medication routine , that is , physicians prescribing admitting orders . The primary outcome was time to the first unplanned contact to a physician after discharge ( i.e. , general practitioner , emergency department visit , or readmission ) during 3-month follow-up . Secondary outcomes included other health-related outcomes , for example , length of in-hospital stay , mortality , and quality of life . Results Time to the first unplanned contact to a physician was 14.9 days ( 95 % confidence interval , 8.9–21.0 ) in the intervention group compared with 27.3 days ( 95 % confidence interval , 18.9–35.7 ) in the controls ( P = 0.05 ) . Overall , no statistically significant differences were seen in the secondary outcomes apart from “ number of ” and “ time to first ” emergency department visits , which were in favor of the intervention group . A marked hesitation of the ward physicians to comply with recommendations was noted ( 18 % ) . Conclusions The study showed that the patients receiving usual care had a significantly longer time to the first unplanned contact to a physician after discharge ; however , the fact that less than 1 of 5 recommendations was adopted by the physicians raises concerns as to whether this finding could be attributable to the intervention WHAT IS KNOWN AND OBJECTIVE Drug-related problems ( DRPs ) occur frequently in hospitalized patients . Patient discharge from the intensive care unit ( ICU ) to a non-ICU ward is one of the most challenging and high-risk transitions of care due to the number of medications , and the complexity and acuity of the medical conditions that characterize this patient group . Pharmacists could play an important role in preventing DRPs . This study was undertaken to evaluate the impact on the number and severity of drug-related problems by assigning a clinical pharmacist to the transfer process from ICU to wards . METHODS The study was a r and omized controlled multicentre trial conducted at the Hospital Network of Antwerp between December 2010 and January 2012 . The clinical pharmacist performed a medical review in both the intervention and control group . Recommendations for drug therapy changes were immediately communicated in the intervention group but were kept blinded in the control group . The primary outcome was expressed as the number of implemented recommendations for drug therapy changes . Differences between groups were calculated using mixed effects binary logistic regression . RESULTS Drug-related problems were found in the medical records of 360 of the 600 participants ( 60 % ) . A total of 743 recommendations could be made , 375 in the intervention group and 368 in the control group . 54·1 % of these problems were adjusted on time in the intervention group vs. 12·8 % in the control group . Of 743 recommendations , 24·8 % were judged by the expert group as major , 13·1 % as moderate , 53.4 % as minor and 8·9 % as having no clinical impact . The odds of implementing recommendations of drug therapy changes in the intervention group were 10 times the odds of implementing recommendations of drug therapy changes in the control group ( odds ratio = 10·1 ; 95%CI [ 6·3 - 16·1 ] ; P < 0·001 ) , even after accounting for differences in types of DRP between the groups ( odds ratio = 15·6 ; 95%CI [ 9·4 - 25·9 ] ; P < 0·001 ) . WHAT IS NEW AND CONCLUSION The integration of a clinical pharmacist at the transfer point from ICU to ward led to a significant reduction in DRPs Elderly patients are vulnerable to medication errors and adverse drug events due to increased morbidity , polypharmacy and inappropriate interactions . The objective of this study was to investigate whether systematic medication review and counselling performed by a clinical pharmacist and clinical pharmacologist would reduce length of in-hospital stay in elderly patients admitted to an acute ward of internal medicine . A r and omized , controlled study of 100 patients aged 70 years or older was conducted in an acute ward of internal medicine in Denmark . Intervention arm : a clinical pharmacist conducted systematic medication review s after an experienced medical physician had prescribed the patients ' medication . Information was collected from medical charts , interview with the patients and data base registration s of drug purchase . Subsequently , medication histories were conferred with a clinical pharmacologist and advisory notes recommending medication changes were completed . Physicians were not obliged to comply with the recommendations . Control arm : medication was review ed by usual routine in the ward . Primary end-point was length of in-hospital stay . In addition , readmissions , mortality , contact to primary healthcare and quality of life were measured at 3-month follow-up . In the intervention arm , the mean length of in-hospital stay was 239.9 hr ( 95 % CI : 190.2 - 289.6 ) and in the control arm : 238.6 hr ( 95 % CI : 137.6 - 339.6 ) , which was neither a statistical significant nor a clinical ly relevant difference . Moreover , no differences were observed for any of the secondary end-points . Systematic medication review and medication counselling did not show any effect on in-hospital length of stay in elderly patients when admitted to an acute ward of internal medicine 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 BACKGROUND One important task for physicians is to optimize their patients ' medication regimen . Involvement of clinical pharmacists who have specific training in drug regimen design has been associated with improved patient outcomes for specific medical conditions , eg , hypertension and anticoagulation . This prospect i ve , r and omized trial investigated whether a single consultation by a clinical pharmacist with high-risk patients and their primary physicians would result in improved prescribing outcomes . METHODS Patients at risk for medication-related problems were identified and r and omized to receive a pharmacotherapy consultation ( consult group ) or usual medical care ( control group ) . Outcomes , including the number of drugs , number of doses per day , cost of medications , and patient reports of adverse effects , were recorded at baseline and at 6 months following the intervention . RESULTS Fifty-six subjects were evaluable : 29 in the control group , and 27 in the consult group . Six months after the consultation , the number of drugs , the number of doses , and the 6-month drug costs all decreased in the consult group and increased in the control group ; the net difference was 1.1 drugs ( P = .004 ) , 2.15 doses per day ( P = .007 ) , $ 586 per year ( P = .008 ) . The side effects score improved by 1.8 points more in the consult group compared with the control group ( P = NS ) . Similarly , the prescribing convenience score in the consult group improved by 1.4 points more than that of the control group ( P = NS ) . CONCLUSIONS This study demonstrates several important benefits of integration of a clinical pharmacist into a primary care setting , including improvement in cost and simplification of the medication regimen with no reduction in quality of care Objective : To determine whether two different educational interventions would reduce polypharmacy in out patients receiving ten ( 10 ) or more active medications at the Denver Veterans Affairs Center . Design : 292 patients were r and omized into three ( 3 ) groups : Control ( n=88 ) ; simple notification of primary care provider ( n=102 ) ; intensive notification , provision of pharmacy profiles , compliance index , and chart review by senior clinician with recommendations ( n=104 ) . Setting : Veterans Affairs Medical Center affiliated with the University of Colorado Health Sciences Center . Patients / Participants : All patients receiving greater than ten ( 10 ) active medications who are followed by clinic staff at the Denver VAMC . The mean age was 62 years ( range 26–88 ) and 96 % were male . Interventions : The simple notification group received only a single letter recommending that the patient ’s number of medications be reduced . The intensive notification group received more sophisticated intervention with a chart review , two letters with calculation of patient compliance , and individualized suggestions for reduction in polypharmacy . The control group received no intervention . Measurements and main results : Control patients had significantly less reduction in polypharmacy then either the simple or intensive intervention groups at four months ( p=0.028 ) . There was no significant difference between the intervention groups ( p=0.189 ) . By six months the difference was no longer significant . Conclusions : A simple intervention can result in a significant reduction in the number of medications prescribed to patients with polypharmacy . The authors were unable to show that a more complex intervention result ed in a further reduction in polypharmacy INTRODUCTION We study the impact of a pharmacist consult clinic on the care of elderly out patients based on the Health Belief Model that the perceived benefits ( improvement in medication knowledge , clinical status and perception ) and attached barriers ( cost and number of medication and adverse drug reactions ) can influence health behaviour ( medication compliance ) . MATERIAL S AND METHODS A r and omised controlled study of 136 eligible patients with risk factors for non-compliance , using Zelen 's design , was conducted in a hospital-based geriatric outpatient clinic from November 2001 to June 2002 . All patients were assessed for outcome variables at baseline and 2 months later . RESULTS One hundred and twenty-six patients were included in the intention-to-treat analysis . There were 104 pharmacist interventions with a physician acceptance rate of 76 % . There was a significant improvement in medication knowledge with regards to indication ( P = 0.03 ) and the composite dose , frequency and indication score ( P = 0.06 ) , as well as a decrease in residual adverse drug reactions that persisted at month 2 and cost avoidance of dollars 387.28 over 2 months . There was no significant difference in perception , clinical status or decrease in number of medications . The intervention group showed an improvement in adjusted compliance ( odds ration [ OR ] = 2.52 ; 90 % confidence interval [ CI ] , 1.09 to 5.83 ) based on the ordered logistic regression model . Perception of severity of illness at baseline ( OR = 1.30 ; 90 % CI , 1.04 to 1.62 ) , number of medication remembering methods ( OR = 1.87 ; 90 % CI , 1.08 to 3.25 ) and the use of routine habits ( OR = 4.48 ; 90 % CI , 1.51 to 13.28 ) and medication aids ( OR = 3.68 ; 90 % CI , 1.04 to 13.06 ) significantly affected compliance . CONCLUSION The addition of a pharmacist consult clinic to the management of selected geriatric out patients can improve compliance , with the attendant benefits of improving medication knowledge , cost avoidance and reducing residual adverse drug reactions The effect of medication profile review by a clinical pharmacist on prescribing in a general medicine clinic was studied . Patients who were receiving five or more prescription or nonprescription medications were r and omly assigned to an intervention group ( n = 315 ) or a control group ( n = 257 ) . A clinical pharmacist review ed the medication profile of each intervention group patient on the day before the patient 's clinic visit and attached a written profile review to the medical record for study by the physician during the visit . After each clinic day , the pharmacist obtained up date d records of patients in both groups and collected data on the number and cost of medications ordered before and after the visits . After the clinic visits , the average number of medications and the average monthly medication cost per patient decreased by 0.21 and $ 0.60 , respectively , for the intervention group , compared with increases of 0.48 and $ 3.31 for the control group . The net result of a single profile review was a decrease of 0.69 prescription per patient , for a monthly medication cost savings of $ 3.91 . The number and cost of medications that were discontinued were significantly higher in the intervention group . The intervention group also had significantly fewer drugs added for previously documented medical problems . Medication profile review by a clinical pharmacist reduced both the number and cost of drugs for patients receiving five or more medications Inappropriate prescribing is particularly common in older patients and is associated with adverse drug events ( ADEs ) , hospitalization , and wasteful utilization of re sources . We r and omized 400 hospitalized patients aged ≥65 years to receive either the usual pharmaceutical care ( control ) or screening with STOPP/START criteria followed up with recommendations to their attending physicians ( intervention ) . The Medication Appropriateness Index ( MAI ) and Assessment of Underutilization ( AOU ) index were used to assess prescribing appropriateness , both at the time of discharge and for 6 months after discharge . Unnecessary polypharmacy , the use of drugs at incorrect doses , and potential drug – drug and drug – disease interactions were significantly lower in the intervention group at discharge ( absolute risk reduction 35.7 % , number needed to screen to yield improvement in MAI = 2.8 ( 95 % confidence interval 2.2–3.8 ) ) . Underutilization of clinical ly indicated medications was also reduced ( absolute risk reduction 21.2 % , number needed to screen to yield reduction in AOU = 4.7 ( 95 % confidence interval 3.4–7.5 ) ) . Significant improvements in prescribing appropriateness were sustained for 6 months after discharge OBJECTIVE To assess whether home-based medication review by a pharmacist for at-risk older patients in a primary care setting can reduce hospital admissions . DESIGN R and omised controlled trial comparing home-based medication review with st and ard care . SETTING Home-based medication review of 136 patients registered with one general practice . METHOD Study participants were over 80 years of age , living at home , taking four or more medicines , and had at least one additional medicines-related risk factor . The intervention comprised two home visits by a community pharmacist who educated the patient/carer about their medicines , noted any pharmaceutical care issues , assessed need for an adherence aid , and subsequently met with the lead GP to agree on actions . MAIN OUTCOME MEASURE Total non-elective hospital admissions within 6 months . Secondary outcomes included number of deaths , care home admissions and quality of life ( EQ-5d ) . Impact on number of medicines prescribed was also assessed . RESULTS At 6 months , no difference in hospital admissions ( 21 intervention versus 20 control P = 0.80 ) , and no difference in care home admissions or deaths were detected between groups . There was a small ( non-significant ) decrease in quality of life in the intervention group . There was a statistically significant reduction in the mean number of medicines prescribed ( -0.87 items in favour of the intervention group , 95 % confidence interval -1.66 to -0.08 , P = 0.03 ) . CONCLUSIONS No positive impact on clinical outcomes or quality of life was demonstrated , however , this intervention did appear to reduce prescribing . This is in line with other evidence and suggests that this form of intervention may not have a clear health gain , but may lead to modest savings in terms of reduced prescribing . Future research should focus on whether such a prescribing effect would make this type of intervention cost effective 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 INTRODUCTION Australia has a rapidly ageing population , especially in rural areas , and strategies to address medicines and the elderly are particularly relevant . The aims of this 18 month study , therefore , were to : ( 1 ) determine the influence of a medication review on the quality of life of elderly ambulatory patients managed by a general practitioner ; and ( 2 ) assess the impact of the medication review process on health outcomes such as medication-related hospital admissions in ambulant elderly patients actively managed by their GP . METHODS The study was conducted within the area serviced by the rural Riverina Division of General Practice , New South Wales , Australia . Patients were identified by clinical audit , and recruited to the study if they met the inclusion criteria of being : older than 65 years , ambulant , living independently and on five or more medications . The study sample consisted of 402 participants ( 156 men , 38.8 % ; 246 women , 61.2 % ) . Fifty-eight participants withdrew from the study for a variety of reasons . A two-group ( intervention , control ) pre- and post-intervention r and omized study design was utilized . Quality of life was assessed using SF-36 . The medication history and clinical details of the 202 study participants were review ed by the project pharmacist and their GP . Medication changes were suggested to patients by their GP and follow-up SF36 and review of hospitalisation episodes were conducted after 6 months . RESULTS 3382 medications were identified as being taken , an average of 8.4 medications per patient . After the initial medication review , the study pharmacist suggested an alteration in dose , form or frequency for 687 medications in the intervention group . The GPs recommended an alteration in 243 of patient medications . Of the entire study population ( n = 402 ) , only two participants ' admission to hospital was specifically attributed to medication-related issues . There were no significant differences between the quality of life assessment s for the combined groups ; however , the intervention group recorded significantly higher scores in two of the nine dimensions measured : vitality ( p 0.009 ) and mental health ( p 0.0001 ) , at the post-intervention assessment . CONCLUSION While the intervention did not reduce hospitalisation episodes and only led to a modest improvement in quality of life , the development of a mutually acceptable form of face-to-face pharmacist/GP medication review , identification of potentially serious adverse drug reactions , identification of previously unreported complementary medicine use , and enhanced GP awareness of the risks of polypharmacy were positive outcomes of the study Background and objectives Several studies have been conducted to determine the frequency and characteristics of adverse drug reactions ( ADRs ) in elderly population s , focusing on those leading to hospital admission . However , most of these studies have been limited in their ability to assess risk factors , particularly the renal status of patients . Thus , the aim of this prospect i ve study was to assess the incidence of ADRs and associated factors leading to hospital admissions in the elderly population . Methods All patients aged ≥65 years admitted to the Toulouse University Hospital through the Emergency Department during four non-consecutive weeks in 2002–3 were included in this study except for patients in ambulatory care or admitted for intentional overdoses . The characteristics of patients admitted for a suspected ADR were compared with those of patients admitted for other reasons . Results The incidence of hospital admissions for ADRs was 8.37 per 100 admissions ( 95 % CI 6.52 , 10.52 ) , corresponding to 66 patients with ADRs among 789 admissions . The most important factors associated with ADRs were the number of drugs being taken ( odds ratio [ OR ] 1.18 ; 95 % CI 1.08 , 1.29 ) , self-medication ( OR 2.34 ; 95 % CI 1.18 , 4.66 ) , use of antithrombotics ( Anatomic Therapeutic and Chemical [ ATC ] classification B01 ; OR 2.26 ; 95 % CI 1.33 , 3.88 ) and use of antibacterial drugs ( ATC J01 ; OR 4.04 ; 95 % CI 1.50 , 10.83 ) . Surprisingly , exposure to drugs for acid-related disorders was associated with a low risk of ADRs ( OR 0.26 ; 95 % CI 0.09 , 0.76 ) . Conclusion A significant incidence of ADRs leading to hospital admissions was found among elderly people . Our study showed that there is a need to increase the availability of information for the general public concerning potential ADRs due to self-medication and for prescribers concerning ADRs due to drug-drug interactions and polypharmacy BACKGROUND Medication review by pharmacists is increasingly being implemented in the primary care setting and has been incorporated into the new pharmacy contract in the UK . This study aims to determine the cost effectiveness of home-based medication review in older people . METHODS This economic evaluation was based on a r and omised controlled trial ( the HOMER [ HOME-based medication Review ] trial ) . Patients aged > 80 years ( n = 872 ) were recruited if admitted as an emergency to an acute or community hospital in Norfolk or Suffolk ( any cause ) , returning to their own home or warden-controlled accommodation , and taking two or more drugs daily on discharge . Patients r and omised to the intervention group received two home visits by a pharmacist within 2 and 8 weeks of discharge to educate patients and carers about their drugs , remove out-of- date drugs , inform GPs of drug reactions or interactions and inform the local pharmacist if an adherence aid was needed . The control arm received usual care . Economic evaluation was performed from the UK NHS perspective , with follow-up for 6 months and cost data from 2000 . Re source use data were collected from hospital episode statistics and from a sample of GP records of trial participants . Intervention , hospital , ambulance and general practice costs were considered to determine average costs and incremental cost-effectiveness ratios . Use of the EQ-5D question naire permitted outcomes to be expressed as QALYs . Probabilistic sensitivity analysis was employed to calculate cost-effectiveness acceptability curves . RESULTS Mortality and admission data were available for 829 of 855 patients included in the study ( 415 intervention and 414 control patients ) . Of those patients r and omised to the intervention group , 358 had a medication review at a total intervention cost of 51,622 pound ( or 124 pound per r and omised patient ) . The intervention did not reduce hospital admissions . The average cost per intervention group patient was 1695 pound compared with 1424 pound for control patients . The incremental cost per life year gained through the intervention was 33,541 pound . The incremental cost per QALY gained in the intervention was 54,454 pound . Sensitivity analysis suggested a 25 % probability that home-based medication review is cost effective using a threshold of 30,000 pound per QALY . CONCLUSION The current policy imperative for implementing medicines review needs to be reconsidered in the light of the findings of this study : a small , non significant gain in quality of life , no reduction in hospital admissions and a low probability of cost effectiveness OBJECTIVES To test the efficacy of a medication use improvement program developed specifically for home health agencies . The program addressed four medication problems identified by an expert panel : unnecessary therapeutic duplication , cardiovascular medication problems , use of psychotropic drugs in patients with possible adverse psychomotor or adrenergic effects , and use of nonsteroidal antiinflammatory drugs ( NSAIDs ) in patients at high risk of peptic ulcer complications . It used a structured collaboration between a specially trained clinical pharmacist and the patients ' home-care nurses to improve medication use . DESIGN Parallel-group , r and omized controlled trial . SETTING Two of the largest home health agencies in the United States . PARTICIPANTS Study subjects were consenting Medicare patients aged 65 and older admitted to participating agency offices from October 1996 through September 1998 , with a projected home healthcare duration of at least 4 weeks and at least one study medication problem . INTERVENTION Qualifying patients were r and omized to usual care or usual care with the medication improvement program . MEASUREMENTS Medication use was measured during an in-home interview , with container inspection at baseline and at follow-up ( between 6 and 12 weeks ) by interviewers unaware of treatment assignment . The trial endpoint was the proportion of patients with medication use improvement according to predefined criteria at follow-up . RESULTS There were 259 r and omized patients with completed follow-up interviews : 130 in the intervention group and 129 with usual care . Medication use improved for 50 % of intervention patients and 38 % of control patients , an attributable improvement of 12 patients per 100 ( 95 % confidence interval ( CI ) = 0.0 - 24.0 , P = .051 ) . The intervention effect was greatest for therapeutic duplication , with improvement for 71 % of intervention and 24 % of control patients , an attributable improvement of 47 patients per 100 ( 95 % CI = 20 - 74 , P = .003 ) . Use of cardiovascular medications also improved more frequently in intervention patients : 55 % vs 18 % , attributable improvement 37 patients per 100 ( 95 % CI = 9 - 66 , P = .017 ) . There were no significant improvements for the psychotropic medication or NSAID problems . There was no evidence of adverse intervention effects : new medication problems , more agency nurse visits , or increased duration of home health care . CONCLUSIONS A program congruent with existing personnel and practice s of home health agencies improved medication use in a vulnerable population and was particularly effective in reducing therapeutic duplication AIMS To examine the characteristics of medication-related problems occurring in people with diabetes admitted to hospital and to identify risk factors for medication-related problems . METHODS A retrospective cohort study of medication-related problems occurring in patients admitted to an adult , inner-city Australian teaching hospital was conducted over two-years . The risk factors associated with medication-related problems were identified using r and om effect logistic regression . RESULTS There were 9530 admissions of people with diabetes involving 5205 individuals over a two-year period . Medication-related problems were associated with 686 ( 7.2 % ) admissions involving 571 individuals ( 11.0 % ) . The most common medication-related problems were medication errors ( 64.1 % ) associated with hypoglycaemia and unintentional overdose . Five factors were significantly associated with medication-related problems : female gender [ odds ratio ( OR ) 1.30 , 95 % confidence intervals ( CI ) 1.11 - 1.52 ] , age of 18 - 50 years ( OR 2.32 , CI 1.85 - 2.91 ) , single marital status ( OR 1.46 , CI 1.24 - 1.74 ) , mental and behavioural problems ( OR 1.74 , 1.43 - 2.11 ) , and a comorbidity index score of at least one ( OR 1.35 - 1.67 ) . CONCLUSIONS Five significant risk factors were associated with medication-related problems in people with diabetes admitted to hospital . These risks need to be considered when developing care plans and interventions to prevent medication-related problems for individuals with diabetes Abstract Objective . The aim of the study was to assess the effect on prescription quality and quality of life after intervention with prescription review s and promotion of patient participation in primary care . Design . A r and omized controlled study with three groups : ( A ) controls , ( B ) prescription review sent to physician , and ( C ) as in B and with a current comprehensive medication record sent to the patient . Setting . The municipality of Örebro , Sweden ( 130 000 inhabitants ) . Intervention . The study focused on the easiest possible intervention to increase prescription quality and thereby increase quality of life . The intervention should be cost-efficient , focus on colleague-to-colleague advice , and be possible to perform in the primary health care centre without additional re sources such as a pharmacist . Subjects . 150 patients recently discharged from hospital . Inclusion criteria were : ≥ 75 years , ≥ five drugs and living in ordinary homes . Main outcome measures . Quality of life ( EQ-5D index , EQ VAS ) and quality of prescriptions . Results . Extreme polypharmacy was common and persistent in all three groups and this was accompanied by an unchanged frequency of drug-risk indicators . There was a low EQ-5D index and EQ VAS in all three groups throughout the study . No statistically significant differences were found anywhere between the groups . Conclusion . The intervention seems to have had no effect on quality of prescriptions or quality of life . This underlines the major challenge of finding new strategies for improving prescription quality to improve patient outcome measures such as quality of life and reduce the known risks of polypharmacy for the elderly BACKGROUND Medication-related problems that lead to hospitalization have been the subject of many studies , many of which were limited to 1 hospital or lacked patient follow-up . Furthermore , little information exists on potential risk factors associated with preventable medication-related hospitalizations . METHODS A prospect i ve multicenter study was conducted to determine the frequency and patient outcomes of medication-related hospital admissions . A case-control design was used to determine risk factors for potentially preventable admissions . All unplanned admissions in 21 hospitals were assessed during 40 days . Controls were patients admitted for elective surgery . Cases and controls were followed up until hospital discharge . The frequency of medication-related hospital admissions , potential preventability , and outcomes were assessed . For potentially preventable medication-related admissions , risk factors were identified in the case-control study . RESULTS Almost 13,000 unplanned admissions were screened , of which 714 ( 5.6 % ) were medication related . Almost half ( 46.5 % ) of these admissions were potentially preventable , result ing in 332 case patients matched with 332 controls . Outcomes were favorable in most patients . The main determinants of preventable medication-related hospital admissions were impaired cognition ( odds ratio , 11.9 ; 95 % confidence interval , 3.9 - 36.3 ) , 4 or more comorbidities ( 8.1 ; 3.1 - 21.7 ) , dependent living situation ( 3.0 ; 1.4 - 6.5 ) , impaired renal function ( 2.6 ; 1.6 - 4.2 ) , nonadherence to medication regimen ( 2.3 ; 1.4 - 3.8 ) , and polypharmacy ( 2.7 ; 1.6 - 4.4 ) . CONCLUSIONS Adverse drug events are an important cause of hospitalizations , and almost half are potentially preventable . The identified risk factors provide a starting point for preventing medication-related hospital admissions OBJECTIVE To evaluate the effectiveness of a telephonic medication therapy management ( MTM ) service on reducing hospitalizations among home health patients . SETTING Forty r and omly selected , geographically diverse home health care centers in the United States . DESIGN Two-stage , r and omized , controlled trial with 60-day follow-up . All Medicare- insured home health care patients were eligible to participate . Twenty-eight consecutive patients within each care center were recruited and r and omized to usual care or MTM intervention . The MTM intervention consisted of the following : ( 1 ) initial phone call by a pharmacy technician to verify active medications ; ( 2 ) pharmacist-provided medication regimen review by telephone ; and ( 3 ) follow-up pharmacist phone calls at day seven and as needed for 30 days . The primary outcome was 60-day all-cause hospitalization . DATA COLLECTION Data were collected from in-home nursing assessment s using the OASIS-C. Multivariate logistic regression modeled the effect of the MTM intervention on the probability of hospitalization while adjusting for patients ' baseline risk of hospitalization , number of medications taken daily , and other OASIS-C data elements . PRINCIPAL FINDINGS A total of 895 patients ( intervention n = 415 , control n = 480 ) were block-r and omized to the intervention or usual care . There was no significant difference in the 60-day probability of hospitalization between the MTM intervention and control groups ( Adjusted OR : 1.26 , 95 percent CI : 0.89 - 1.77 , p = .19 ) . For patients within the lowest baseline risk quartile ( n = 232 ) , the intervention group was three times more likely to remain out of the hospital at 60 days ( Adjusted OR : 3.79 , 95 percent CI : 1.35 - 10.57 , p = .01 ) compared to the usual care group . CONCLUSIONS This MTM intervention may not be effective for all home health patients ; however , for those patients with the lowest-risk profile , the MTM intervention prevented patients from being hospitalized at 60 days |
13,573 | 29,240,924 | Results Current evidence indicates that n-3 LC-PUFAs administered during pregnancy or breastfeeding have no effect on the skills or cognitive development of children in later stages of development .
Evidence regarding the improvement of cognitive function during childhood and youth or in attention deficit/hyperactivity disorder is inconclusive .
Moreover , it is still unclear if n-3 LC-PUFAs can improve cognitive development or prevent cognitive decline in young or older adults | Context The increasing number of studies on the effects of n-3 long-chain polyunsaturated fatty acids ( LC-PUFAs ) on health , particularly cognition , in the last 5 years reflects the growing interest in this area of research .
Objective The aim for this systematic review was to evaluate the scientific evidence published in the last 5 years ( 2012 - 2017 ) on the effects of n-3 LC-PUFA intake on cognition , cognitive development , and cognitive decline to determine whether n-3 LC-PUFAs support cognitive development and prevent cognitive decline . | Oxidative stress , inflammation , and increased cholesterol levels are all mechanisms that have been associated with Alzheimer ’s disease ( AD ) pathology . Several epidemiologic studies have reported a decreased risk of AD with fish consumption . This pilot study was design ed to evaluate the effects of supplementation with omega-3 fatty acids alone ( ω-3 ) or omega-3 plus alpha lipoic acid ( ω-3 + LA ) compared to placebo on oxidative stress biomarkers in AD . The primary outcome measure was peripheral F2-isoprostane levels ( oxidative stress measure ) . Secondary outcome measures included performance on : Mini-Mental State Examination ( MMSE ) , Activities of Daily Living/Instrumental Activities of Daily Living ( ADL/IADL ) , and Alzheimer Disease Assessment Scale-cognitive subscale ( ADAS-cog ) . Thirty-nine AD subjects were r and omized to one of three groups : 1 ) placebo , 2 ) ω-3 , or 3 ) ω-3 + LA for a treatment duration of 12 months . Eighty seven percent ( 34/39 ) of the subjects completed the 12-month intervention . There was no difference between groups at 12 months in peripheral F2-isoprostane levels ( p = 0.83 ) . The ω-3 + LA and ω-3 were not significantly different than the placebo group in ADAS-cog ( p = 0.98 , p = 0.86 ) and in ADL ( p = 0.15 , p = 0.82 ) . Compared to placebo , the ω-3+LA showed less decline in MMSE ( p < 0.01 ) and IADL ( p= 0.01 ) and the ω-3 group showed less decline in IADL ( p < 0.01 ) . The combination of ω-3+LA slowed cognitive and functional decline in AD over 12 months . Because the results were generated from a small sample size , further evaluation of the combination of omega-3 fatty acids plus alpha-lipoic acid as a potential treatment in AD is warranted OBJECTIVES Docosahexaenoic acid ( DHA ; 22:6 n-3 ) and arachidonic acid ( AA ; 20:4 n-6 ) are important for development of the central nervous system in mammals . There is a growth spurt in the human brain during the last trimester of pregnancy and the first postnatal months , with a large increase in the cerebral content of AA and DHA . The fetus and the newborn infant depend on maternal supply of DHA and AA . Our hypothesis was that maternal intake of DHA during pregnancy and lactation is marginal and that high intake of this fatty acid would benefit the child . We examined the effect of supplementing pregnant and lactating women with very-long-chain n-3 polyunsaturated fatty acids ( PUFAs ; cod liver oil ) on mental development of the children , compared with maternal supplementation with long-chain n-6 PUFAs ( corn oil ) . METHODS The study was r and omized and double-blinded . Pregnant women were recruited in week 18 of pregnancy to take 10 mL of cod liver oil or corn oil until 3 months after delivery . The cod liver oil contained 1183 mg/10 mL DHA , 803 mg/10 mL eicosapentaenoic acid ( 20:5 n-3 ) , and a total of 2494 mg/10 mL summation operator n-3 PUFAs . The corn oil contained 4747 mg/10 mL linoleic acid ( 18:2 n-6 ) and 92 mg/10 mL alpha-linolenic acid ( 18:3 n-3 ) . The amount of fat-soluble vitamins was identical in the 2 oils ( 117 micro g/mL vitamin A , 1 micro g/mL vitamin D , and 1.4 mg/mL dl-alpha-tocopherol ) . A total of 590 pregnant women were recruited to the study , and 341 mothers took part in the study until giving birth . All infants of these women were scheduled for assessment of cognitive function at 6 and 9 months of age , and 262 complied with the request . As part of the protocol , 135 subjects from this population were invited for intelligence testing with the Kaufman Assessment Battery for Children ( K-ABC ) at 4 years of age . Of the 135 invited children , 90 came for assessment . Six children did not complete the examination . The K-ABC is a measure of intelligence and achievement design ed for children aged 2.5 years through 12.5 years . This multisubtest battery comprises 4 scales : Sequential Processing , Simultaneous Processing , Achievement ( not used in the present study ) , and Nonverbal Abilities . The Sequential Processing and Simultaneous Processing scales are hypothesized to reflect the child 's style of problem solving and information processing . Scores from these 2 scales are combined to form a Mental Processing Composite , which serves as the measure of intelligence in the K-ABC . RESULTS We received dietary information from 76 infants ( 41 in the cod liver oil group and 35 in the corn oil group ) , documenting that all of them were breastfed at 3 months of age . Children who were born to mothers who had taken cod liver oil ( n = 48 ) during pregnancy and lactation scored higher on the Mental Processing Composite of the K-ABC at 4 years of age as compared with children whose mothers had taken corn oil ( n = 36 ; 106.4 [ 7.4 ] vs 102.3 [ 11.3 ] ) . The Mental Processing Composite score correlated significantly with head circumference at birth ( r = 0.23 ) , but no relation was found with birth weight or gestational length . The children 's mental processing scores at 4 years of age correlated significantly with maternal intake of DHA and eicosapentaenoic acid during pregnancy . In a multiple regression model , maternal intake of DHA during pregnancy was the only variable of statistical significance for the children 's mental processing scores at 4 years of age . CONCLUSION Maternal intake of very-long-chain n-3 PUFAs during pregnancy and lactation may be favorable for later mental development of children Background : Intestinal damage and malabsorption caused by chronic environmental enteropathy are associated with growth faltering seen in infants in less-developed countries . Evidence has suggested that supplementary omega-3 ( n−3 ) long-chain PUFAs ( LC-PUFAs ) might ameliorate this damage by reducing gastrointestinal inflammation . LC-PUFA supplementation may also benefit cognitive development . Objective : We tested whether early n−3 LC-PUFA supplementation improves infant intestinal integrity , growth , and cognitive function . Design : A r and omized , double-blind , controlled trial [ 200 mg DHA and 300 mg EPA or 2 mL olive oil/d for 6 mo ] was conducted in a population of 172 rural Gambian infants aged 3–9 mo . The primary endpoints were anthropometric measures and gut integrity [ assessed by using urinary lactulose : mannitol ratios ( LMRs ) ] . Plasma fatty acid status , intestinal mucosal inflammation ( fecal calprotectin ) , daily morbidity , and cognitive development ( 2-step means-end test and an attention assessment ) were secondary endpoints . Results : PUFA supplementation result ed in a significant increase in plasma n−3 LC-PUFA concentrations ( P < 0.001 for both DHA and EPA ) and midupper arm circumference ( MUAC ) ( effect size : 0.31 z scores ; 95 % CI : 0.06 , 0.56 ; P = 0.017 ) at 9 mo of age . At 12 mo , MUAC remained greater in the intervention group , and we observed significant increases in skinfold thicknesses ( P ≤ 0.022 for all ) . No other significant differences between treatment groups were detected for growth or LMRs at 9 mo or for secondary outcomes . Conclusions : Fish-oil supplementation successfully increased plasma n−3 fatty acid status . However , in young , breastfed Gambian infants , the intervention failed to improve linear growth , intestinal integrity , morbidity , or selected measures of cognitive development . The trial was registered at www.is rct n.org as IS RCT N66645725 Abstract This trial investigated the efficacy of omega-3 polyunsaturated fatty acid ( n-3 PUFA ) treatment for improving depressive symptoms and cognitive performance in patients with coronary artery disease ( CAD ) participating in cardiac rehabilitation . Patients with CAD aged 45 to 80 years were r and omized to receive either 1.9-g/d n-3 PUFA treatment or placebo for 12 weeks . Depressive symptoms were measured using the Hamilton Depression Rating Scale ( HAM-D , primary outcome ) and the Beck Depression Inventory II ( BDI-II ) . Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria were used to identify a depressive episode at baseline . Cognitive performance was measured using a st and ardized battery for vascular cognitive impairment . In 92 patients ( age , 61.7 ± 8.7 y ; 76 % male , 40 % depressed ; HAM-D , 6.9 ± 5.9 ; BDI-II , 12.3 ± 10.9 ; n = 45 n-3 PUFA , n = 47 placebo ) , depression decreased ( HAM-D , F3,91 = 2.71 and P = 0.049 ; BDI-II , F3,91 = 6.24 and P < 0.01 ) , and cognitive performance improved ( attention/processing speed , F1,91 = 5.57 , P = 0.02 ; executive function , F1,91 = 14.64 , P < 0.01 ; visuospatial memory , F1,91 = 4.01 , P = 0.04 ) over cardiac rehabilitation . Omega-3 PUFA treatment increased plasma eicosapentaenoic acid ( F1,29 = 33.29 , P < 0.01 ) and docosahexaenoic acid ( F1,29 = 15.29 , P < 0.01 ) concentrations but did not reduce HAM-D ( F3,91 = 1.59 , P = 0.20 ) or BDI-II ( F3,91 = 0.46 , P = 0.50 ) scores compared with placebo . Treatment did not improve cognitive performance ; however , n-3 PUFAs significantly increased verbal memory compared with placebo in a subgroup of nondepressed patients ( F1,54 = 4.16 , P = 0.04 ) . This trial suggests that n-3 PUFAs do not improve depressive and associated cognitive symptoms in those with CAD . The possible benefits of n-3 PUFAs for verbal memory may warrant investigation in well-powered studies Objective : To test the hypothesis that higher levels of red blood cell ( RBC ) docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) have a protective association with domain-specific cognitive function in women aged 65 years and older . Methods : A total of 2,157 women with normal cognition enrolled in a clinical trial of postmenopausal hormone therapy were followed with annual cognitive testing for a median of 5.9 years . In this retrospective cohort study , we assessed the relationship between prer and omization RBC DHA + EPA levels and a ) cognitive measures at baseline , and b ) cognitive change over time . Endpoints were composite cognitive function and performance in 7 cognitive domains : fine motor speed , verbal memory , visual memory , spatial ability , verbal knowledge , verbal fluency , and working memory . Results : After adjustment for demographic , clinical , and behavioral characteristics , no significant ( p < 0.01 ) cross-sectional cognitive differences were found between women in the high and low DHA + EPA tertiles at the time of the first annual cognitive battery . In addition , no significant ( p < 0.01 ) differences were found between the high and low DHA + EPA tertiles in the rate of cognitive change over time . Conclusions : We did not find an association between RBC DHA + EPA levels and age-associated cognitive decline in a cohort of older , dementia-free women Depressive symptoms may increase the risk of progressing from mild cognitive impairment ( MCI ) to dementia . Consumption of n-3 PUFA may alleviate both cognitive decline and depression . The aim of the present study was to investigate the benefits of supplementing a diet with n-3 PUFA , DHA and EPA , for depressive symptoms , quality of life ( QOL ) and cognition in elderly people with MCI . We conducted a 6-month double-blind , r and omised controlled trial . A total of fifty people aged > 65 years with MCI were allocated to receive a supplement rich in EPA ( 1·67 g EPA + 0·16 g DHA/d ; n 17 ) , DHA ( 1·55 g DHA + 0·40 g EPA/d ; n 18 ) or the n-6 PUFA linoleic acid ( LA ; 2·2 g/d ; n 15 ) . Treatment allocation was by minimisation based on age , sex and depressive symptoms ( Geriatric Depression Scale , GDS ) . Physiological and cognitive assessment s , question naires and fatty acid composition of erythrocytes were obtained at baseline and 6 months ( completers : n 40 ; EPA n 13 , DHA n 16 , LA n 11 ) . Compared with the LA group , GDS scores improved in the EPA ( P=0·04 ) and DHA ( P=0·01 ) groups and verbal fluency ( Initial Letter Fluency ) in the DHA group ( P=0·04 ) . Improved GDS scores were correlated with increased DHA plus EPA ( r 0·39 , P=0·02 ) . Improved self-reported physical health was associated with increased DHA . There were no treatment effects on other cognitive or QOL parameters . Increased intakes of DHA and EPA benefited mental health in older people with MCI . Increasing n-3 PUFA intakes may reduce depressive symptoms and the risk of progressing to dementia . This needs to be investigated in larger , depressed sample s with MCI BACKGROUND Docosahexaenoic acid ( DHA ) is important for brain function , and its status is dependent on dietary intakes . Therefore , individuals who consume diets low in omega-3 ( n-3 ) polyunsaturated fatty acids may cognitively benefit from DHA supplementation . Sex and apolipoprotein E genotype ( APOE ) affect cognition and may modulate the response to DHA supplementation . OBJECTIVES We investigated whether a DHA supplement improves cognitive performance in healthy young adults and whether sex and APOE modulate the response . DESIGN Healthy adults ( n = 176 ; age range : 18 - 45 y ; nonsmoking and with a low intake of DHA ) completed a 6-mo r and omized , placebo-controlled , double-blind intervention in which they consumed 1.16 g DHA/d or a placebo . Cognitive performance was assessed by using a computerized cognitive test battery . For all tests , z scores were calculated and clustered into cognitive domains as follows : episodic and working memory , attention , reaction time ( RT ) of episodic and working memory , and attention and processing speed . ANCOVA was conducted with sex and APOE as independent variables . RESULTS RTs of episodic and working memory improved with DHA compared with placebo [ mean difference ( 95 % CI ) : -0.18 SD ( -0.33 , -0.03 SD ) ( P = 0.02 ) and -0.36 SD ( -0.58 , -0.14 SD ) ( P = 0.002 ) , respectively ] . Sex × treatment interactions occurred for episodic memory ( P = 0.006 ) and the RT of working memory ( P = 0.03 ) . Compared with the placebo , DHA improved episodic memory in women [ 0.28 SD ( 0.08 , 0.48 SD ) ; P = 0.006 ] and RTs of working memory in men [ -0.60 SD ( -0.95 , -0.25 SD ) ; P = 0.001 ] . APOE did not affect cognitive function , but there were some indications of APOE × sex × treatment interactions . CONCLUSIONS DHA supplementation improved memory and the RT of memory in healthy , young adults whose habitual diets were low in DHA . The response was modulated by sex . This trial was registered at the New Zeal and Clinical Trials Registry ( http://www.anzctr.org.au/default.aspx ) as ACTRN12610000212055 A number of trials have been undertaken to assess whether the intake of omega-3 long-chain polyunsaturated fatty acids ( n-3 LCPUFA ) during pregnancy can influence the neurological development of the offspring , yet no consensus from these trials has been reached . We aim ed to investigate the long-term effects ( 12 years ) of fish oil supplementation in pregnancy on neurodevelopment , including cognition , language and fine motor skills . In a follow up of a previously published r and omised controlled trial of 98 pregnant women , their children were assessed at 12 years of age using a battery of neurodevelopmental assessment s. Fifty participants were assessed at 12 years , with 25 participant ’s mothers receiving fish oil supplementation , and 25 receiving control capsules . There were no significant differences for any of the assessment measures completed . Our data indicate that fish oil supplementation during pregnancy does not influence the cognition , language or fine motor skills of children in late primary school ( 12 years of age ) BACKGROUND No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline . We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention ( physical activity , cognitive training , and nutritional advice ) , alone or in combination , compared with placebo , on cognitive decline . METHODS The Multidomain Alzheimer Preventive Trial was a 3-year , multicentre , r and omised , placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco . Participants were non-demented , aged 70 years or older , and community-dwelling , and had either relayed a spontaneous memory complaint to their physician , limitations in one instrumental activity of daily living , or slow gait speed . They were r and omly assigned ( 1:1:1:1 ) to either the multidomain intervention ( 43 group sessions integrating cognitive training , physical activity , and nutrition , and three preventive consultations ) plus omega 3 polyunsaturated fatty acids ( ie , two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid ) , the multidomain intervention plus placebo , omega 3 polyunsaturated fatty acids alone , or placebo alone . A computer-generated r and omisation procedure was used to stratify patients by centre . All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment , but were unblinded to the multidomain intervention component . Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment . The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests ( free and total recall of the Free and Cued Selective Reminding test , ten Mini-Mental State Examination orientation items , Digit Symbol Substitution Test , and Category Naming Test ) in the modified intention-to-treat population . The trial was registered with Clinical Trials.gov ( NCT00672685 ) . FINDINGS 1680 participants were enrolled and r and omly allocated between May 30 , 2008 , and Feb 24 , 2011 . In the modified intention-to-treat population ( n=1525 ) , there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group . Between-group differences compared with placebo were 0·093 ( 95 % CI 0·001 to 0·184 ; adjusted p=0·142 ) for the combined intervention group , 0·079 ( -0·012 to 0·170 ; 0·179 ) for the multidomain intervention plus placebo group , and 0·011 ( -0·081 to 0·103 ; 0·812 ) for the omega 3 polyunsaturated fatty acids group . 146 ( 36 % ) participants in the multidomain plus polyunsaturated fatty acids group , 142 ( 34 % ) in the multidomain plus placebo group , 134 ( 33 % ) in the polyunsaturated fatty acids group , and 133 ( 32 % ) in the placebo group had at least one serious emerging adverse event . Four treatment-related deaths were recorded ( two in the multidomain plus placebo group and two in the placebo group ) . The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events . INTERPRETATION The multidomain intervention and polyunsaturated fatty acids , either alone or in combination , had no significant effects on cognitive decline over 3 years in elderly people with memory complaints . An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined , particularly in real-world setting s. FUNDING French Ministry of Health , Pierre Fabre Research Institute , Gerontopole , Exhonit Therapeutics , Avid Radiopharmaceuticals OBJECTIVE : To test the hypothesis that supplementation with the long chain polyunsaturated fatty acids docosahexaenoic acid ( DHA ) and arachidonic acid ( AA ) to very low birth weight ( VLBW ) infants would improve long-term cognitive functions and influence neuroanatomical volumes and cerebral cortex measured by MRI . METHODS : The current study is a follow-up of a r and omized , double-blinded , placebo-controlled study of supplementation with high-dose DHA ( 0.86 % ) and AA ( 0.91 % ) to 129 VLBW infants fed human milk . Ninety-eight children participated at 8 years follow-up and completed a broad battery of cognitive tests . Eighty-one children had cerebral MRI scans of acceptable quality . RESULTS : There were no significant differences between the intervention group and the control group on any of the cognitive measures . Equally , MRI data on segmental brain volumes and cerebral cortex volume , area , and thickness suggested no overall group effect . CONCLUSIONS : This study is the first long-term follow-up of a r and omized controlled trial with supplementation of DHA and AA to human milk fed VLBW infants investigating both cognitive functions and brain macrostructure measured by MRI . No cognitive or neuroanatomical effects of the supplementation were detected at 8 years of age OBJECTIVE To determine whether supplementation with the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic ( EPA ) and docosahexaenoic acid ( DHA ) affects behavioral symptoms and cognitive impairments in children 6 - 12 years of age diagnosed with attention-deficit/hyperactivity disorder ( ADHD ) . STUDY DESIGN The r and omized , double-blind placebo-controlled 16 weeks trial was conducted with 95 children diagnosed with ADHD according to DSM-IV criteria . Behavior was assessed by parents , teachers and investigators using st and ardized rating scales and question naires . Further outcome variables were working memory , speed of information processing and various measures of attention . For a subgroup of 81 participants , erythrocyte membrane fatty acid composition was analyzed before and after the intervention . RESULTS Supplementation with the omega-3 fatty acid mix increased EPA and DHA concentrations in erythrocyte membranes and improved working memory function , but had no effect on other cognitive measures and parent- and teacher-rated behavior in the study population . Improved working memory correlated significantly with increased EPA , DHA and decreased AA ( arachidonic acid ) Background Cognitive impairment is a prevalent health problem in older people and its global prevalence tends to increase parallel to the extended life expectancy in world . The beneficial effect of ω-3 PUFAs on cognitive impairment has been demonstrated in some experimental and cohort studies . In this study we aim ed to assess the effect of low dose docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) supplementation on cognitive status in the elderly . Methods In a double-blind , r and omized placebo-controlled study , 199 individuals aged ≥65 years with normal or mild to moderate cognition impairment were assigned to receive either 180 mg of DHA plus 120 mg of EPA or placebo for 180 days . Cognitive status was assessed using Mini-Mental State Examination ( MMSE ) and Abbreviated Mental Test ( AMT ) score . Results MMSE and AMT scores were not different at the time of allocation [ 18.84 ( 5.37 ) , 18.55 ( 5.12 ) , ( P = 0.70 ) and 4.81 ( 2.79 ) and 4.64 ( 2.77 ) , ( P = 0.67 ) respectively ] and over 6 months between the ω-3 PUFA- and placebo- treated groups [ 18.57 ( 5.21 ) , 18.39 ( 5.10 ) , ( P = 0.80 ) and 4.64 ( 2.77 ) and 4.48 ( 2.69 ) and ( P = 0.67 ) ] . The participants were categorized based on MMSE score into normal cognition , mild and moderate cognitive impairment . After multivariate adjustment , there was no significant difference among categorized groups regarding the ω-3 PUFA effect except in normal cognition group , that amount of decline in AMT in ω-3 poly unsaturated fatty acids ( PUFAs ) was less than placebo group . Conclusions It seems that prescription of low dose ω-3 PUFAs for 6 months had no significant beneficial effects on improvement of cognition or prevention of cognitive decline in older people Objective : Intake of n-3 polyunsaturated fatty acids ( n-3 PUFAs ) may protect against mild cognitive impairment ( MCI ) . However , there is still a lack of the n-3 PUFAs intervention in the elderly with MCI in China . The aim of the present study was to investigate the effect of n-3 PUFA supplementation on cognitive function in the Chinese elderly with MCI . Methods : Eighty six MCI individuals aged 60 years or older were r and omly assigned to receive either n-3 PUFAs ( 480 mg DHA and 720 mg EPA per day , n = 44 ) or placebo ( olive oil , n = 42 ) capsules . The changes of cognitive functions were assessed using Basic Cognitive Aptitude Tests ( BCAT ) . Results : The mean age of participants was 71 years old , and 59 % of the participants were men . n-3 PUFA supplementation was associated with improved total BCAT scores , perceptual speed , space imagery efficiency , and working memory ( p < 0.01 ) , but not with mental arithmetic efficiency or recognition memory ( p > 0.05 ) . Subgroup analysis by sex showed that n-3 PUFAs significantly improved perceptual speed ( p = 0.001 ) , space imagery efficiency ( p = 0.013 ) , working memory ( p = 0.018 ) , and total BCAT scores ( p = 0.000 ) in males . However , in females , the significant beneficial effects can only be observed in perceptual speed ( p = 0.027 ) , space imagery efficiency ( p = 0.006 ) , and total BCAT scores ( p = 0.015)—not working memory ( p = 0.113 ) . Conclusion : n-3 PUFAs can improve cognitive function in people with MCI . Further studies with different fish oil dosages , longer intervention periods , and larger sample sizes should be investigated before definite recommendations can be made Findings from epidemiological and observational studies have indicated that diets high in omega-3 polyunsaturated fatty acids ( PUFAs ) such as docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) may reduce the risk of cognitive decline and Alzheimer ’s disease ( AD ) . To determine if increasing intake of DHA and EPA through supplementation is beneficial to cognition and mood in individuals with cognitive impairment no dementia ( CIND ) or Alzheimer ’s disease ( AD ) a four month , r and omised , double-blind , placebo controlled study was conducted . Fifty-seven participants with CIND and nineteen with AD were r and omised to receive either omega-3 PUFAs ( 600 mg EPA and 625 mg DHA per day ) or placebo ( olive oil ) over a four month period . Elevating depleted levels of EPA and DHA through supplementation in individuals with CIND or AD was found to have negligible beneficial effect on their cognition or mood . These findings confirm an overall negligible benefit of omega-3 PUFA supplementation for those with cognitive impairment and dementia . More intervention studies need to be undertaken with longer study duration s and larger sample sizes . It may prove fruitful to examine effects of different doses as well as effects in other dementia subtypes Objective : To investigate effects of omega-3 polyunsaturated fatty acids ( n-3 PUFA ) docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) on attention , literacy , and behavior in children with ADHD . Method : Ninety children were r and omized to consume supplements high in EPA , DHA , or linoleic acid ( control ) for 4 months each in a crossover design . Erythrocyte fatty acids , attention , cognition , literacy , and Conners ’ Parent Rating Scales ( CPRS ) were measured at 0 , 4 , 8 , 12 months . Results : Fifty-three children completed the treatment . Outcome measures showed no significant differences between the three treatments . However , in children with blood sample s ( n = 76 - 46 ) , increased erythrocyte EPA + DHA was associated with improved spelling ( r = .365 , p < .001 ) and attention ( r = −.540 , p < .001 ) and reduced oppositional behavior ( r = −.301 , p < .003 ) , hyperactivity ( r = −.310 , p < .001 ) , cognitive problems ( r = −.326 , p < .001 ) , Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; DSM-IV ) hyperactivity ( r = −.270 , p = .002 ) and DSM-IV inattention ( r = −.343 , p < .001 ) . Conclusion : Increasing erythrocyte DHA and EPA via dietary supplementation may improve behavior , attention , and literacy in children with ADHD In the present study , we tested whether elderly with a high dietary intake of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) would have higher cognitive test scores and greater brain volume than those with low dietary intake of these fatty acids . Data were obtained from the Prospect i ve Investigation of the Vasculature in Uppsala Seniors ( PIVUS ) cohort . The dietary intake of EPA and DHA was determined by a 7-day food protocol in 252 cognitively healthy elderly ( 122 females ) at the age of 70 years . At age 75 , participants ' global cognitive function was examined , and their brain volumes were measured by magnetic resonance imaging ( MRI ) . Three different multivariate linear regression models were applied to test our hypothesis : model A ( adjusted for gender and age ) , model B ( additionally controlled for lifestyle factors , e.g. , education ) , and model C ( further controlled for cardiometabolic factors , e.g. , systolic blood pressure ) . We found that the self-reported 7-day dietary intake of EPA and DHA at the age of 70 years was positively associated with global gray matter volume ( P < 0.05 , except for model C ) and increased global cognitive performance score ( P < 0.05 ) . However , no significant associations were observed between the dietary intake of EPA and DHA and global white matter , total brain volume , and regional gray matter , respectively . Further , no effects were observed when examining cognitively impaired ( n = 27 ) elderly as separate analyses . These cross-sectional findings suggest that dietary intake of EPA and DHA may be linked to improved cognitive health in late life but must be confirmed in patient studies The utility of multicenter cognitive test methodology and result ant outcomes of supplementation with docosahexaenoic acid in healthy 4-year-old children was evaluated in a r and omized , placebo-controlled , double-blind study . Subjects received 400-mg/d docosahexaenoic acid ( n = 85 ) or matching placebo ( n = 90 ) in capsules for 4 months . Cognitive tests included the Leiter-R Test of Sustained Attention , Peabody Picture Vocabulary Test , Day-Night Stroop Test , and Conners ' Kiddie Continuous Performance Test . The relationship of docosahexaenoic acid levels in capillary whole blood from a sub sample ( n = 93 ) with scores on cognitive tests was evaluated . For each test , results indicated that changes from baseline to end of treatment were not statistically significantly different between the docosahexaenoic acid group and the placebo group . Regression analysis , however , yielded a statistically significant positive ( P = .018 ) association between the blood level of docosahexaenoic acid and higher scores on the Peabody Picture Vocabulary Test , a test of listening comprehension and vocabulary acquisition Beneficial effects of omega-3 fatty acids have been reported for several psychiatric disorders , particularly for depression . Association studies show a relationship between omega-3 intake and depression risk . Meta-analyses of clinical trials have shown a moderate effect of supplementation on depressive symptoms , but not on normal mood states . Few studies have investigated effects on cognition . The purpose of this study was to examine effects of omega-3 supplements on cognition and mood of recovered depressed individuals . Seventy-one participants were r and omized to receive either omega-3 or placebo for four weeks in a r and omized double-blind design . Results showed small effects of omega-3 supplementation on aspects of emotional decision-making and on self-reported states of depression and tension . Some of the effects were confounded by learning effects . No significant effects were observed on memory , attention , cognitive reactivity and depressive symptoms . While inconclusive , the present findings may indicate that omega-3 supplementation has selective effects on emotional cognition and mood in recovered depressed participants IMPORTANCE Observational data have suggested that high dietary intake of saturated fat and low intake of vegetables may be associated with increased risk of Alzheimer disease . OBJECTIVE To test the effects of oral supplementation with nutrients on cognitive function . DESIGN , SETTING , AND PARTICIPANTS In a double-masked r and omized clinical trial ( the Age-Related Eye Disease Study 2 [ AREDS2 ] ) , retinal specialists in 82 US academic and community medical centers enrolled and observed participants who were at risk for developing late age-related macular degeneration ( AMD ) from October 2006 to December 2012 . In addition to annual eye examinations , several vali date d cognitive function tests were administered via telephone by trained personnel at baseline and every 2 years during the 5-year study . INTERVENTIONS Long-chain polyunsaturated fatty acids ( LCPUFAs ) ( 1 g ) and /or lutein ( 10 mg)/zeaxanthin ( 2 mg ) vs placebo were tested in a factorial design . All participants were also given varying combinations of vitamins C , E , beta carotene , and zinc . MAIN OUTCOMES AND MEASURES The main outcome was the yearly change in composite scores determined from a battery of cognitive function tests from baseline . The analyses , which were adjusted for baseline age , sex , race , history of hypertension , education , cognitive score , and depression score , evaluated the differences in the composite score between the treated vs untreated groups . The composite score provided an overall score for the battery , ranging from -22 to 17 , with higher scores representing better function . RESULTS A total of 89 % ( 3741/4203 ) of AREDS2 participants consented to the ancillary cognitive function study and 93.6 % ( 3501/3741 ) underwent cognitive function testing . The mean ( SD ) age of the participants was 72.7 ( 7.7 ) years and 57.5 % were women . There were no statistically significant differences in change of scores for participants r and omized to receive supplements vs those who were not . The yearly change in the composite cognitive function score was -0.19 ( 99 % CI , -0.25 to -0.13 ) for participants r and omized to receive LCPUFAs vs -0.18 ( 99 % CI , -0.24 to -0.12 ) for those r and omized to no LCPUFAs ( difference in yearly change , -0.03 [ 99 % CI , -0.20 to 0.13 ] ; P = .63 ) . Similarly , the yearly change in the composite cognitive function score was -0.18 ( 99 % CI , -0.24 to -0.11 ) for participants r and omized to receive lutein/zeaxanthin vs -0.19 ( 99 % CI , -0.25 to -0.13 ) for those r and omized to not receive lutein/zeaxanthin ( difference in yearly change , 0.03 [ 99 % CI , -0.14 to 0.19 ] ; P = .66 ) . Analyses were also conducted to assess for potential interactions between LCPUFAs and lutein/zeaxanthin and none were found to be significant . CONCLUSIONS AND RELEVANCE Among older persons with AMD , oral supplementation with LCPUFAs or lutein/zeaxanthin had no statistically significant effect on cognitive function . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00345176 Background Krill oil , rich in n-3 ( omega-3 ) polyunsaturated fatty acids ( PUFAs ) incorporated in phosphatidylcholine , has been reported to have many effects on physiological function . However , there are few studies using psychophysiological methods published that describe the effects of krill oil on brain function . We investigated the influence of ingestion of krill oil on cognitive function in elderly subjects by using near-infrared spectroscopy and electroencephalography . Methods A r and omized , double-blind , parallel-group comparative study design was adopted . Forty-five healthy elderly males aged 61–72 years were assigned to receive 12 weeks of treatment with : medium-chain triglycerides as placebo ; krill oil , which is rich in n-3 PUFAs incorporated in phosphatidylcholine ; or sardine oil , which is abundant in n-3 PUFAs incorporated in triglycerides . Changes in oxyhemoglobin concentrations in the cerebral cortex during memory and calculation tasks were measured . The P300 component of event-related potentials was also measured during a working memory task . Results During the working memory task , changes in oxyhemoglobin concentrations in the krill oil and sardine oil groups were significantly greater than those in the medium-chain triglyceride group at week 12 . The differential value for P300 latency in the krill oil group was significantly lower than that in the medium-chain triglyceride group at week 12 . With regard to the calculation task , changes in oxyhemoglobin concentrations in the krill oil group were significantly greater than those in the medium-chain triglyceride group at week 12 . Conclusion This study provides evidence that n-3 PUFAs activate cognitive function in the elderly . This is especially the case with krill oil , in which the majority of n-3 PUFAs are incorporated into phosphatidylcholine , causing it to be more effective than sardine oil , in which n-3 PUFAs are present as triglycerides Higher intake of seafish or oil rich in long-chain omega-3 polyunsaturated fatty acids ( LC-n3-FA ) may be beneficial for the aging brain . We tested in a prospect i ve interventional design whether high levels of supplementary LC-n3-FA would improve cognition , and addressed potential mechanisms underlying the effects . Sixty-five healthy subjects ( 50 - 75 years , 30 females ) successfully completed 26 weeks of either fish oil ( 2.2 g/day LC-n3-FA ) or placebo intake . Before and after the intervention period , cognitive performance , structural neuroimaging , vascular markers , and blood parameters were assayed . We found a significant increase in executive functions after LC-n3-FA compared with placebo ( P = 0.023 ) . In parallel , LC-n3-FA exerted beneficial effects on white matter microstructural integrity and gray matter volume in frontal , temporal , parietal , and limbic areas primarily of the left hemisphere , and on carotid intima media thickness and diastolic blood pressure . Improvements in executive functions correlated positively with changes in omega-3-index and peripheral brain-derived neurotrophic factor , and negatively with changes in peripheral fasting insulin . This double-blind r and omized interventional study provides first-time evidence that LC-n3-FA exert positive effects on brain functions in healthy older adults , and eluci date s underlying mechanisms . Our findings suggest novel strategies to maintain cognitive functions into old age OBJECTIVE The current study aim ed to investigate the effects of eicosapentaenoic acid (EPA)-rich and docosahexaenoic acid (DHA)-rich supplementations on cognitive performance and functional brain activation . DESIGN A double-blind , counterbalanced , crossover design , with a 30-day washout period between two supplementation periods ( EPA-rich and DHA-rich ) was employed . Functional magnetic resonance imaging scans were obtained during performance of Stroop and Spatial Working Memory tasks prior to supplementation and after each 30-day supplementation period . RESULTS Both supplementations result ed in reduced ratio of arachidonic acid to EPA levels . Following the EPA-rich supplementation , there was a reduction in functional activation in the left anterior cingulate cortex and an increase in activation in the right pre central gyrus coupled with a reduction in reaction times on the colour-word Stroop task . By contrast , the DHA-rich supplementation led to a significant increase in functional activation in the right pre central gyrus during the Stroop and Spatial Working Memory tasks , but there was no change in behavioural performance . CONCLUSIONS By extending the theory of neural efficiency to the within-subject neurocognitive effects of supplementation , we concluded that following the EPA-rich supplementation , participants ' brains worked ' less hard ' and achieved a better cognitive performance than prior to supplementation . Conversely , the increase in functional activation and lack of improvement in time or accuracy of cognitive performance following DHA-rich supplementation may indicate that DHA-rich supplementation is less effective than EPA-rich supplementation in enhancing neurocognitive functioning after a 30-day supplementation period in the same group of individuals Background Omega-3 fatty acids are dietary essentials , and the current low intakes in most modern developed countries are believed to contribute to a wide variety of physical and mental health problems . Evidence from clinical trials indicates that dietary supplementation with long-chain omega-3 may improve child behavior and learning , although most previous trials have involved children with neurodevelopmental disorders such as attention-deficit/hyperactivity disorder ( ADHD ) or developmental coordination disorder ( DCD ) . Here we investigated whether such benefits might extend to the general child population . Objectives To determine the effects of dietary supplementation with the long-chain omega-3 docosahexaenoic acid ( DHA ) on the reading , working memory , and behavior of healthy schoolchildren . Design Parallel group , fixed-dose , r and omized , double-blind , placebo-controlled trial ( RCT ) . Setting Mainstream primary schools in Oxfordshire , UK ( n = 74 ) . Participants Healthy children aged 7–9 years initially underperforming in reading ( ≤33rd centile ) . 1376 invited , 362 met study criteria . Intervention 600 mg/day DHA ( from algal oil ) , or taste/color matched corn/soybean oil placebo . Main Outcome Measures Age-st and ardized measures of reading , working memory , and parent- and teacher-rated behavior . Results ITT analyses showed no effect of DHA on reading in the full sample , but significant effects in the pre-planned subgroup of 224 children whose initial reading performance was ≤20th centile ( the target population in our original study design ) . Parent-rated behavior problems ( ADHD-type symptoms ) were significantly reduced by active treatment , but little or no effects were seen for either teacher-rated behaviour or working memory . Conclusions DHA supplementation appears to offer a safe and effective way to improve reading and behavior in healthy but underperforming children from mainstream schools . Replication studies are clearly warranted , as such children are known to be at risk of low educational and occupational outcomes in later life . Trial Registration Clinical Trials.gov NCT01066182 and Controlled-Trials.com IS RCT Rationale Epidemiological studies have suggested a beneficial effect of fish oil supplementation in halting the initial progression of Alzheimer ’s disease . However , it remains unclear whether fish oil affects cognitive function in older people with mild cognitive impairment ( MCI ) . Objectives This study investigated the effects of fish oil supplementation on cognitive function in elderly person with MCI . Methods This was a 12-month , r and omised , double-blind , placebo-controlled study using fish oil supplementation with concentrated docosahexaenoic acid ( DHA ) . Thirty six low-socioeconomic-status elderly subjects with MCI were r and omly assigned to receive either concentrated DHA fish oil ( n = 18 ) or placebo ( n = 18 ) capsules . The changes of memory , psychomotor speed , executive function and attention , and visual-constructive skills were assessed using cognitive tests . Secondary outcomes were safety and tolerability of the DHA concentrate . Results The fish oil group showed significant improvement in short-term and working memory ( F = 9.890 ; ηp2 = 0.254 ; p < 0.0001 ) , immediate verbal memory ( F = 3.715 ; ηp2 = 0.114 ; p < 0.05 ) and delayed recall capability ( F = 3.986 ; ηp2 = 0.121 ; p < 0.05 ) . The 12-month change in memory ( p < 0.01 ) was significantly better in the fish oil group . Fish oil consumption was well tolerated , and the side effects were minimal and self-limiting . Conclusions This study suggested the potential role of fish oil to improve memory function in MCI subjects . Studies with larger sample sizes , longer intervention periods , different fish oil dosages and genetic determinations should be investigated before definite recommendations can be made BACKGROUND ω3 fatty acids ( ω3 FAs ) may slow the rate of decline in cognitive performance in mild forms of cognitive impairment and Alzheimer 's disease ( AD ) . However , the relationship between changes of plasma ω3 FA levels and cognitive performance , as well as effects of gender , are poorly known . OBJECTIVE To study the effect of 6-month administration of DHA-rich ω3 FA supplementation on plasma FA profiles in patients with mild to moderate AD in relation to cognitive performance and gender . This investigation is part of the OmegAD Study . METHODS 174 AD patients ( 74 ± 9 years ) were r and omized to a daily intake of 2.3 g ω3 FA or placebo for 6 months ; subsequently all received the ω3 FA preparation for the next 6 months . Baseline as well as changes in plasma levels of the main ω3 FAs in 165 patients , while receiving ω3 FA supplementation for 6 months , were analyzed for association to cognitive performance ( assessed by ADAS-cog and MMSE scores ) as well as to gender . RESULTS Preservation of cognitive functioning , assessed by ADAS-cog or its sub-items ( but not MMSE ) scores , was significantly associated to increasing plasma ω3 FA levels over time . Thus , the higher ω3 FA plasma levels rose , the lower was the rate of cognitive deterioration . This effect was not related to gender ; since although females displayed higher ω3 FA plasma levels than did males after 6 months of supplementation , this difference disappeared when adjusted for body weight . CONCLUSIONS Since our study suggests dose-response relationships between plasma levels of ω3 FA and preservation of cognition , future ω3 FA trials in patients with mild AD should consider exploring grade d ( and body weight adjusted ) doses of ω3 FA BACKGROUND Docosahexanoic acid ( DHA ) is an important constituent of the brain . Evidence from well- design ed intervention trials of the long-term benefits of increasing DHA intake during pregnancy has been sparse . OBJECTIVE We evaluated global cognition , behavior , and attention at age 5 y in the offspring of Mexican women who participated in a r and omized controlled trial of prenatal DHA supplementation . DESIGN A total of 1094 women were r and omly assigned to receive 400 mg of either DHA or placebo/d from 18 to 22 wk of pregnancy until delivery . We assessed cognitive development and behavioral and executive functioning , including attention , in 797 offspring at age 5 y ( 82 % of 973 live births ) with the use of the McCarthy Scales of Children 's Abilities ( MSCA ) , the parental scale of the Behavioral Assessment System for Children , Second Edition ( BASC-2 ) , and the Conners ' Kiddie Continuous Performance Test ( K-CPT ) . We compared the groups on raw scores , T-scores , and st and ardized scores , as appropriate . We examined heterogeneity by the quality of the home environment , maternal intelligence , and socioeconomic status . RESULTS There were no group differences for MSCA scores ( P > 0.05 ) , but the positive effect of the home environment at 12 mo on general cognitive abilities was attenuated in the DHA group compared with in the placebo group ( P-interaction < 0.05 ) . There were no differences between groups on the BASC-2 . On the K-CPT , offspring in the DHA group showed improved mean ± SD T-scores compared with those of the placebo group for omissions ( DHA : 47.6 ± 10.3 ; placebo : 49.6 ± 11.2 ; P < 0.01 ) with no differences ( P > 0.05 ) for the other K-CPT scores or of the proportion who were clinical ly at risk of attention deficit hyperactivity disorders after Bonferroni correction for multiple comparisons . CONCLUSION Prenatal exposure to DHA may contribute to improved sustained attention in preschool children . This trial was registered at clinical trials.gov as NCT00646360 The omega-3 fatty acid docosahexaenoic acid ( DHA ) is essential for nervous system and retinal development and there is evidence to suggest that DHA deficiencies increase with normal aging . A triple-blind placebo-controlled r and omized repeated- measures trial was conducted with 74 healthy participants , aged 45 - 77 years . Cognitive and visual acuity measures and plasma levels of DHA were determined at baseline and after 90 days of administration of either HiDHA ( ® ) ( Clover Corp. , Sydney , NSW , Australia : 1000 mg of tuna oil ; comprising 252 mg DHA , 60 mg EPA and 10 mg vitamin E ) or placebo ( 1000 mg soybean oil ) . Ninety days of DHA supplementation was found to significantly raise both plasma DHA and total ω-3 plasma levels in the treatment group , as well as significantly lower total ω-6 levels . However , no significant effects of DHA supplementation on cognitive functioning were found . For participants with corrected vision , the group receiving DHA were found to have significantly better right eye visual acuity posttreatment in comparison with the placebo group ( F(1,22 ) = 7.651 ; p = 0.011 ; partial η(2 ) = 0.258 ) n-3 Long-chain PUFA ( LC-PUFA ) intake during infancy is important for neurodevelopment ; however , previous studies of n-3 LC-PUFA supplementation have been inconclusive possibly due to an insufficient dose and limited methods of assessment . The present study aim ed to evaluate the effects of direct supplementation with high-dose fish oil ( FO ) on infant neurodevelopmental outcomes and language . In the present r and omised , double-blind , placebo-controlled trial , 420 healthy term infants were assigned to receive a DHA-enriched FO supplement ( containing at least 250 mg DHA/d and 60 mg EPA/d ) or a placebo ( olive oil ) from birth to 6 months . Assessment occurred at 18 months via the Bayley Scales of Infant and Toddler Development ( 3rd edition ; BSID-III ) and the Child Behavior Checklist . Language assessment occurred at 12 and 18 months via the Macarthur-Bates Communicative Development Inventory . The FO group had significantly higher erythrocyte DHA ( P = 0·03 ) and plasma phospholipid DHA ( P = 0·01 ) levels at 6 months of age relative to placebo . In a small subset analysis ( about 40 % of the total population ) , children in the FO group had significantly higher percentile ranks of both later developing gestures at 12 and 18 months ( P = 0·007 ; P = 0·002 , respectively ) and the total number of gestures ( P = 0·023 ; P = 0·006 , respectively ) . There was no significant difference between the groups in the st and ard or composite scores of the BSID-III . The results suggest that improved postnatal n-3 LC-PUFA intake in the first 6 months of life using high-dose infant FO supplementation was not beneficial to global infant neurodevelopment . However , some indication of benefits to early communicative development was observed BACKGROUND Docosahexaenoic acid ( DHA ) accumulates in the hippocampus and frontal lobes of the fetal brain during the last trimester of pregnancy . These areas of the brain contribute to attention and working memory and inhibitory control ( WMIC ) . OBJECTIVE We evaluated the effect of maternal omega-3 ( n-3 ) long-chain polyunsaturated fatty acid supplementation in pregnancy on child attention and WMIC . DESIGN A total of 185 term-born children of mothers who were r and omly allocated to consume 800 mg DHA/d ( treatment ) or a placebo ( control ) from ∼20 wk of gestation until birth were assessed with multiple measures of attention and WMIC at a mean ( ± SD ) of 27 ± 2 mo . Primary outcomes were the average time it took to be distracted when playing with a toy ( distractibility ) and the accuracy of remembering a new hiding location while inhibiting a learned response to search in the previous location ( WMIC ) . RESULTS Assessment s were completed by 81 children in the treatment group ( mean ± SD age : 835 ± 50.4 d ) and 77 children in the control group ( 839 ± 65.6 d ) . There was no effect of supplementation on primary outcomes [ distractibility mean difference : -0.2 s ( 95 % CI : -0.7 , 0.4 s ) ; WMIC mean difference : 8.9 mm ( 95 % CI : -10.6 , 28.3 mm ) ] . There was no difference between DHA-supplemented and control groups except that treatment-group children looked away from the toys fewer times than controls when presented with multiple toys competing for attention but less accurately remembered a repeated hiding location . These secondary effects were not consistent with any other outcomes and may have been a result of chance . Cord plasma DHA was not consistently associated with attention and WMIC . CONCLUSION Maternal DHA supplementation during pregnancy does not enhance attention or WMIC in term-born preschoolers . The DHA for Maternal and Infant Outcomes trial was registered at www.anzctr.org.au as ACTRN1260500056906 Objective To determine if improvements in cognitive outcome detected at 18 months ’ corrected age ( CA ) in infants born <33 weeks ’ gestation receiving a high-docosahexaenoic acid ( DHA ) compared with st and ard-DHA diet were sustained in early childhood . Design Follow-up of a multicentre r and omised controlled trial . R and omisation was stratified for sex , birth weight ( < 1250 vs ≥1250 g ) and hospital . Setting Five Australian tertiary hospitals from 2008 to 2013 . Participants 626 of the 657 participants r and omised between 2001 and 2005 were eligible to participate . Interventions High-DHA ( ≈1 % total fatty acids ) enteral feeds compared with st and ard-DHA ( ≈0.3 % total fatty acids ) from age 2–4 days until term CA . Primary outcome Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence ( WASI ) at 7 years CA . Prespecified subgroup analyses based on the r and omisation strata ( sex , birth weight ) were conducted . Results 604 ( 92 % of the 657 originally r and omised ) consented to participate ( 291 high-DHA , 313 st and ard-DHA ) . To address missing data in the 604 consenting participants ( 22 for primary outcome ) , multiple imputation was performed . The Full Scale IQ was not significantly different between groups ( high-DHA 98.3 , SD 14.0 , st and ard-DHA 98.5 , SD 14.9 ; mean difference adjusted for sex , birthweight strata and hospital −0.3 , 95 % CI −2.9 to 2.2 ; p=0.79 ) . There were no significant differences in any secondary outcomes . In prespecified subgroup analyses , there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour . Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher ( poorer outcome ) compared with girls receiving the st and ard-DHA diet . Conclusions Supplementing the diets of preterm infants with a DHA dose of approximately 1 % total fatty acids from days 2–4 until term CA showed no evidence of benefit at 7 years ’ CA . Trial registration number Australian New Zeal and Clinical Trials Registry : ACTRN12606000327583 Objective To determine the effects of long-chain omega-3 ( LCn-3 ) fatty acids found in fish oil , including eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , on cortical blood oxygen level-dependent ( BOLD ) activity during a working memory task in older adults with subjective memory impairment . Design R and omized , double-blind , placebo-controlled study . Setting Academic medical center . Participants Healthy older adults ( 62–80 years ) with subjective memory impairment , but not meeting criteria for mild cognitive impairment or dementia . InterventionFish oil ( EPA+DHA : 2.4 g/d , n=11 ) or placebo ( corn oil , n=10 ) for 24 weeks . Measurements Cortical BOLD response patterns during performance of a sequential letter n-back working memory task were determined at baseline and week 24 by functional magnetic resonance imaging ( fMRI ) . Results At 24 weeks erythrocyte membrane EPA+DHA composition increased significantly from baseline in participants receiving fish oil ( + 31 % , p≤0.0001 ) but not placebo ( −17 % , p=0.06 ) . Multivariate modeling of fMRI data identified a significant interaction among treatment , visit , and memory loading in the right cingulate ( BA 23/24 ) , and in the right sensorimotor area ( BA 3/4 ) . In the fish oil group , BOLD increases at 24 weeks were observed in the right posterior cingulate and left superior frontal regions during memory loading . A region-of-interest analysis indicated that the baseline to endpoint change in posterior cingulate cortex BOLD activity signal was significantly greater in the fish oil group compared with the placebo group during the 1-back ( p=0.0003 ) and 2-back ( p=0.0005 ) conditions . Among all participants , the change in erythrocyte EPA+DHA during the intervention was associated with performance in the 2-back working memory task ( p = 0.01 ) , and with cingulate BOLD signal during the 1-back ( p = 0.005 ) with a trend during the 2-back ( p = 0.09 ) . Further , cingulate BOLD activity was related to performance in the 2-back condition . Conclusions Dietary fish oil supplementation increases red blood cell omega-3 content , working memory performance , and BOLD signal in the posterior cingulate cortex during greater working memory load in older adults with subjective memory impairment suggesting enhanced neuronal response to working memory challenge Omega-3 fatty acid ( n-3 PUFA ) intake is associated with improved mood and cognition , but r and omized controlled trials addressing the causal nature of such relationships are less clear , especially in healthy , young adults . Stress is one potential mechanism by which n-3 PUFAs may influence mood . Thus the present aim is to evaluate the influence of n-3 PUFA supplementation on stress-induced changes to mood , cognition , and physiological stress markers in healthy , young adults . Using a double-blind , placebo-controlled design , 72 young adults were r and omized to receive 2800mg/day fish oil ( n=36 , 23 females ) or olive oil control ( n=36 , 22 females ) for 35days . Subjects completed measures of mood and cognition before supplementation , and two times after supplementation : following an acute stressor or non-stressful control task . The stress induction was effective in that the stressor impaired mood , including augmenting feelings of tension , anger , confusion and anxiety , reduced accuracy on a cognitive task measuring attentional control and the ability to regulate emotion , and increased salivary cortisol and pro-inflammatory cytokine interleukin-1β ( IL-1β ) . Rated anger and confusion increased with stress in the olive oil group , but remained stable in the fish oil group . However , fish oil had no further effects on mood , cognitive function , cortisol , or IL-1β . Fish oil exerted few effects in stressful and non-stressful situations , consistent with findings showing little influence of n-3 PUFA supplementation on mood and cognition in young , healthy individuals . Potential target population s who would more likely benefit from increased n-3 PUFA intake are discussed Several studies have reported that the supplementation of long-chain polyunsaturated fatty acids ( LCPUFA ) , such as docosahexaenoic acid ( DHA ) , eicosapentaenoic acid ( EPA ) , and arachidonic acid ( ARA ) improve cognitive function in the elderly . However , the doses used in these studies were higher than general dietary LCPUFA intake levels . This r and omized , double-blind , placebo-controlled trial evaluated the effects of low doses of LCPUFA supplementation corresponding to general dietary intake on cognitive function in non-demented elderly Japanese participants . Japanese men aged 55 - 64 years were enrolled and r and omly allocated to the placebo or LCPUFA group . Participants received 4 weeks of supplementation with LCPUFA-containing oil ( DHA , 300 mg/day ; EPA , 100 mg/day ; and ARA , 120 mg/day ) or purified olive oil as placebo . Event-related potential P300 , reflecting cognitive processes , was measured before and after supplementation . A total of 113 participants completed the supplementation period , and the per- protocol analysis included 69 participants . Changes in P300 latency were significantly different between the placebo group ( + 13.6 msec ) and the LCPUFA group ( -1.8 msec ) after supplementation . Significant increases in DHA ( + 0.9 % ) and ARA ( + 0.6 % ) contents in plasma phospholipids were observed in the LCPUFA group ; no changes were observed in the placebo group . Dietary DHA , EPA , and ARA intake were in the normal range for Japan participants and remained unchanged during the study . These results suggest that low doses of LCPUFA supplementation have the potential to improve cognitive function in elderly Japanese men BACKGROUND During fetal and perinatal periods , many nutrients , such as long-chain polyunsaturated fatty acids [ contained in fish oil ( FO ) ] and folate , are important in achieving normal brain development . Several studies have shown the benefits of early nutrition on children 's neurocognitive development . However , the evidence with regard to the attention system is scarce . OBJECTIVES The aim of this study was to analyze the long-term effects of FO , 5-methyltetrahydrofolate ( 5-MTHF ) , or FO+5-MTHF prenatal supplementation on attention networks . DESIGN Participants were 136 children born to mothers from the NUHEAL ( Nutraceuticals for a Healthy Life ) project ( r and omly assigned to receive FO and /or 5-MTHF or placebo prenatal supplementation ) who were recalled for a new examination 8.5 y later . The response conflict-resolution ability ( using congruent and incongruent conditions ) ) , alerting , and spatial orienting of attention were evaluated with behavioral measures ( Attention Network Test ) , electroencephalography/event-related potentials ( ERPs ) , and st and ardized low-resolution brain electromagnetic tomography ( sLORETA ) . RESULTS Children born to mothers supplemented with 5-MTHF alone solved the response conflict more quickly than did the placebo and the FO+5-MTHF groups ( all P < 0.05 ) . Differences between ERP amplitudes for the conflict conditions were also observed . sLORETA analysis showed higher activation of the right midcingulate cortex for the incongruent condition . In addition , a significant slowing down of response speed depending on the warning cue in the 5-MTHF and FO groups was observed . CONCLUSIONS Folate supplementation during pregnancy , rather than FO or FO+5-MTHF supplementation , improves children 's ability to solve response conflicts . This advantage seems to be based on the higher activation of the midcingulate cortex , indicating that early nutrition influences the functionality of specific brain areas involved in executive functions . This trial was registered at clinical trials.gov as NCT01180933 Omega-3 fatty acids ( FAs ) may have neuroprotective properties for psychological health and cognition . The objective of this study was to evaluate the effectiveness of omega-3 FAs ( eicosapentaenoic + docosahexaenoic ; Harris-Schacky [HS]-Omega-3 Index ) on neuropsychological functioning among U.S. Soldiers deployed to Iraq . This r and omized , double-blind , placebo-controlled trial included Soldiers between the ages of 18 and 55 years who were r and omly assigned to either the active treatment group ( n = 44 ) or placebo group ( n = 34 ) . Active treatment was 2.5 g per day of eicosapentaenoic + docosahexaenoic ( Lovaza ; GlaxoSmithKline , Research Triangle Park , North Carolina ) . The placebo was corn oil ethyl esters . HS-Omega-3 Index , a neurocognitive battery ( Central Nervous System-Vital Signs , Morrisville , North Carolina ) , and psychological health scales were assessed at baseline and after 60 days of treatment . Although the results revealed that omega-3 FAs significantly increased the HS-Omega-3 Index ( p = 0.001 ) , there were no significant effects on indices psychological health and neurocognitive functioning by treatment group . Nevertheless , there was a significant inverse correlation between the changes in the HS-Omega-3 Index and daytime sleepiness ( r = 0.30 , p = 0.009 ) . Short-term treatment with 2.5 g of omega-3 FAs did not alter measures of neurocognition or psychological health , but there was evidence of a relationship between omega-3 levels and daytime sleepiness Previous studies in older adults suggested beneficial effects of omega-3 fatty acid ( FA ) supplementation , aerobic exercise , or cognitive stimulation on brain structure and function . However , combined effects of these interventions in patients suffering from mild cognitive impairment ( MCI ) are unknown . Using a r and omized interventional design , we evaluated the effect of combined omega-3 FA supplementation , aerobic exercise and cognitive stimulation ( target intervention ) versus omega-3 FA supplementation and non-aerobic exercise ( control intervention ) on cognitive function and gray matter volume in patients with MCI . Moreover , we analyzed potential vascular , metabolic or inflammatory mechanisms underlying these effects . Twenty-two MCI patients ( 8 females ; 60 - 80years ) successfully completed six months of omega-3 FA intake , aerobic cycling training and cognitive stimulation ( n=13 ) or omega-3 FA intake and non-aerobic stretching and toning ( n=9 ) . Before and after the interventions , cognitive performance , magnetic resonance imaging of the brain at 3 T ( n=20 ) , intima-media thickness of the internal carotid artery and serum markers of glucose control , lipid and B-vitamin metabolism , and inflammation were assessed . Intervention-related changes in gray matter volume of Alzheimer 's disease (AD)-related brain regions , i.e. , frontal , parietal , temporal and cingulate cortex were examined using voxel-based morphometry of high resolution T1-weighted images . After the intervention period , significant differences emerged in brain structure between groups : Gray matter volume decreased in the frontal , parietal and cingulate cortex of patients in the control intervention , while gray matter volume in these areas was preserved or even increased after the target intervention . Decreases in homocysteine levels in the target intervention group were associated with increases in gray matter volume in the middle frontal cortex ( p=0.010 ) . No significant differences in cognitive performance or other vascular , metabolic and inflammatory parameters were observed between groups . This pilot study provides preliminary evidence that omega-3 FA intake combined with aerobic exercise and cognitive stimulation prevents atrophy in AD-related brain regions in MCI patients , compared to omega-3 FA intake plus the control condition of stretching and toning . These promising findings should now be vali date d in a larger interventional trial Beneficial effects of perinatal DHA supply on later neurological development have been reported . We assessed the effects of maternal DHA supplementation on the neurological development of their children . Healthy pregnant women from Spain , Germany , and Hungary were r and omly assigned to a dietary supplement consisting of either fish oil ( FO ) ( 500 mg/d DHA + 150 mg/d EPA ) , 400 μg/d 5-methyltetrahydrofolate , both , or placebo from wk 20 of gestation until delivery . Fatty acids in plasma and erythrocyte phospholipids ( PL ) were determined in maternal blood at gestational wk 20 and 30 and in cord and maternal blood at delivery . Neurological development was assessed with the Hempel examination at the age of 4 y and the Touwen examination at 5.5 y. Minor neurological dysfunction , neurological optimality score ( NOS ) , and fluency score did not differ between groups at either age , but the odds of children with the maximal NOS score increased with every unit increment in cord blood DHA level at delivery in plasma PL ( 95 % CI : 1.094 - 2.262 ) , erythrocyte phosphatidylethanolamine ( 95 % CI : 1.091 - 2.417 ) , and erythrocyte phosphatidylcholine ( 95 % CI : 1.003 - 2.643 ) . We conclude that higher DHA levels in cord blood may be related to a better neurological outcome at 5.5 y of age BACKGROUND The influence of prenatal long-chain polyunsaturated fatty acids ( LC-PUFAs ) and folate on neurologic development remains controversial . OBJECTIVE The objective was to assess the long-term effects of n-3 ( omega-3 ) LC-PUFA supplementation , 5-methyltetrahydrofolate ( 5-MTHF ) supplementation , or both in pregnant women on cognitive development of offspring at 6.5 y of age . DESIGN This was a follow-up study of the NUHEAL ( Nutraceuticals for a Healthier Life ) cohort . Healthy pregnant women in 3 European centers were r and omly assigned to 4 intervention groups . From the 20th week of pregnancy until delivery , they received a daily supplement of 500 mg docosahexaenoic acid ( DHA ) + 150 mg eicosapentaenoic acid [ fish oil ( FO ) ] , 400 μg 5-MTHF , or both or a placebo . Infants received formula containing 0.5 % DHA and 0.4 % arachidonic acid ( AA ) if they were born to mothers receiving FO supplements or were virtually free of DHA and AA until the age of 6 mo if they belonged to the groups that were not supplemented with FO . Fatty acids and folate concentrations were determined in maternal blood at weeks 20 and 30 of pregnancy , at delivery , and in cord blood . Cognitive function was assessed at 6.5 y of age with the Kaufman Assessment Battery for Children ( K-ABC ) . RESULTS We observed no significant differences in K-ABC scores between intervention groups . Higher DHA in maternal erythrocytes at delivery was associated with a Mental Processing Composite Score higher than the 50th percentile in the offspring . CONCLUSION We observed no significant effect of supplementation on the cognitive function of children , but maternal DHA status may be related to later cognitive function in children . This trial was registered at clinical trials.gov as NCT01180933 The evidence relating prenatal supplementation with DHA to offspring neurological development is limited . We investigated the effect of prenatal DHA supplementation on infant brainstem auditory-evoked responses and visual- evoked potentials in a double-blind , r and omized controlled trial in Cuernavaca , Mexico . Pregnant women were supplemented daily with 400 mg DHA or placebo from gestation wk 18 - 22 through delivery . DHA and placebo groups did not differ in maternal characteristics at r and omization or infant characteristics at birth . Brainstem auditory-evoked responses were measured at 1 and 3 mo in 749 and 664 infants , respectively , and visual-evoked potentials were measured at 3 and 6 mo in 679 and 817 infants , respectively . Left-right brainstem auditory-evoked potentials were moderately correlated ( range , 0.26 - 0.43 ; all P < 0.001 ) and left-right visual-evoked potentials were strongly correlated ( range , 0.79 - 0.94 ; all P < 0.001 ) within any assessment . Correlations across visits were modest to moderate ( range , 0.09 - 0.38 ; all P < 0.01 ) . The offspring of DHA-supplemented women did not differ from those of control women with respect to any outcome measure ( all comparisons P > 0.10 ) . We conclude that DHA supplementation during pregnancy did not influence brainstem auditory-evoked responses at 1 and 3 mo or visual-evoked potentials at 3 and 6 mo Omega-3 fatty acids are essential for brain function . We recruited 409 children aged 3 - 13 years ( M=8.27 , SD=2.17 ) for a r and omised controlled trial supplementing with placebo or fish oil capsules ( providing 750 mg docosahexaenoic plus eicosapentaenoic acids , and 60 mg gamma linolenic acid/school day ) for 20 school weeks ( Phase 1 ) followed by one-way crossover to fish oil ( Phase 2 ) . Children undertook assessment s of reading , spelling and non-verbal cognitive development ( Draw-A-Person ) at baseline , 20 and 40 weeks . Teachers completed Conners Behaviour Rating Scales ( CBRS ) . The treatment group showed improvements in Draw-A-Person compared with the placebo during Phase 1 ( p=0.029 ) , with strongest effects in Indigenous 7 - 12 year olds ( p=0.008 ) . The placebo group showed significant within-group improvements after switching to treatment ( p<0.001 ) . There was no treatment effect for reading or spelling , and CBRS data were unable to be analysed . These findings may be understood in the context that sustained school attendance and nutrition interact to produce school-related achievement Background / objectives : Consumption of oily fish more than once per week has been shown to improve cognitive outcomes in children . However , it is unknown whether similar benefits can be achieved by long-term omega-3 fatty acid supplementation . The objective was to investigate the effect of omega-3 fatty acid supplementation during the first 5 years of life on subsequent academic performance in children by conducting a secondary analysis of the CAPS ( Childhood Asthma Prevention Study ) .Subjects/ methods : A total of 616 infants with a family history of asthma were r and omised to receive tuna fish oil ( high in long-chain omega-3 fatty acids , active ) or Sunola oil ( low in omega-3 fatty acids , control ) from the time breastfeeding ceased or at the age of 6 months until the age of 5 years . Academic performance was measured by a nationally st and ardised assessment of literacy and numeracy ( National Assessment Program Literacy and Numeracy ( NAPLAN ) ) in school years 3 , 5 , 7 and 9 . Plasma omega-3 fatty acid levels were measured at regular intervals until 8 years of age . Between-group differences in test scores , adjusted for maternal age , birth weight and maternal education , were estimated using mixed-model regression . Results : Among 239 children , there were no significant differences in NAPLAN scores between active and control groups . However , at 8 years , the proportion of omega-3 fatty acid in plasma was positively associated with the NAPLAN score ( 0.13 s.d . unit increase in score per 1 % absolute increase in plasma omega-3 fatty acid ( 95 % CI 0.03 , 0.23 ) ) . Conclusions : Our findings do not support the practice of supplementing omega-3 fatty acids in the diet of young children to improve academic outcomes . Further exploration is needed to underst and the association between plasma omega-3 fatty acid levels at 8 years and academic performance It has been shown that supplementation with omega-3 improves cognitive performance , especially in infants and toddlers , but it is unknown whether these results are effective in older malnourished children . The aims of this study , therefore , were to investigate the omega-3 supplementation effects in 8- to 12-year-old children and to know which neuropsychological functions improve after three months of intervention in a sample of Mexican children with mild to moderate malnutrition . This study was a r and omized , double-blind , treatment and placebo study of 59 children aged 8 - 12 years who were individually allocated to 2 groups . The duration of the intervention lasted 3 months . Neuropsychological performance was measured at baseline and at 3 months . Results show that more than 50 % of children in the treatment group had greater improvement in 11 of the 18 neuropsychological variables studied . Processing speed , visual-motor coordination , perceptual integration , attention and executive function showed improvement in more than 70 % of the omega-3 supplemented children . This trial was registered at clinical trials.gov as NCT01199120 Four-Year Follow-up of Children Born to Women in a R and omized Trial of Prenatal DHA Supplementation Despite the paucity of evidence , recommendations exist internationally for pregnant women to increase their docosahexaenoic acid ( DHA ) intake to optimize fetal brain development . Our r and omized controlled trial ( RCT ) , in which pregnant women were allocated to 800 mg/d of DHA or matched placebo , showed that children ’s mean cognitive , language , and motor scores did not differ between groups at 18 months , although fewer children in the DHA group had delayed development compared with controls.1 Surprisingly , girls in the DHA group had poorer language scores than girls in the control group.1 Herein we report neurodevelopmental outcomes at 4 years , which is when any subtle to moderate effects on development should have emerged and can be more reliably assessed Objective : Fish oils and multivitamins are two of the most commonly used dietary supplements . Fish oil use may reduce vascular risk factors associated with cognitive decline , thus providing benefits to both heart and brain health . Multivitamins may also have direct effects on brain function . The present study investigated the effects of fish oil , with and without the addition of a multivitamin , on cognitive and cardiovascular function . Methods : In a r and omized , placebo-controlled , double-blind fashion , 160 healthy adults aged 50–70 years were r and omized to receive either 3 g of fish oil ( 240 mg eicosapentaenoic acid [ EPA ] + 240 mg docosahexaenoic acid [ DHA ] ) with a multivitamin , 6 g of fish oil ( 480 mg EPA + 480 mg DHA ) with a multivitamin , or 6 g of fish oil without a multivitamin or a placebo . Cognitive performance , brachial blood pressure , and aortic ( central ) blood pressure were measured at baseline , 6 weeks , and 16 weeks . Results : Treatment allocation had no effect on the primary cognitive outcomes at endpoint . Absolute increases in the red blood cell omega-3/6 ratio were associated with improvements in spatial working memory . The group receiving 6 g fish oil without the multivitamin displayed a significant decrease in aortic pulse pressure and aortic augmentation pressure , two measures of aortic blood pressure and aortic stiffness . Conclusions : Fish oil decreased aortic pulse pressure and augmentation pressure . Reductions in aortic blood pressure were not accompanied by consistent improvements in cognition OBJECTIVE To determine the effects of an eicosapentaenoic acid (EPA)-rich oil and a docosahexaenoic acid (DHA)-rich oil versus an ω-6 polyunsaturated fatty acid-rich safflower oil ( control ) on literacy and behavior in children with attention-deficit/hyperactivity disorder ( ADHD ) in a r and omized controlled trial . METHODS Supplements rich in EPA , DHA , or safflower oil were r and omly allocated for 4 mo to 90 Australian children 7 to 12 y old with ADHD symptoms higher than the 90th percentile on the Conners Rating Scales . The effect of supplementation on cognition , literacy , and parent-rated behavior was assessed by linear mixed modeling . Pearson correlations determined associations between the changes in outcome measurements and the erythrocyte fatty acid content ( percentage of total ) from baseline to 4 mo . RESULTS There were no significant differences between the supplement groups in the primary outcomes after 4 mo . However , the erythrocyte fatty acid profiles indicated that an increased proportion of DHA was associated with improved word reading ( r = 0.394 ) and lower parent ratings of oppositional behavior ( r = 0.392 ) . These effects were more evident in a subgroup of 17 children with learning difficulties : an increased erythrocyte DHA was associated with improved word reading ( r = 0.683 ) , improved spelling ( r = 0.556 ) , an improved ability to divide attention ( r = 0.676 ) , and lower parent ratings of oppositional behavior ( r = 0.777 ) , hyperactivity ( r = 0.702 ) , restlessness ( r = 0.705 ) , and overall ADHD symptoms ( r = 0.665 ) . CONCLUSION Increases in erythrocyte ω-3 polyunsaturated fatty acids , specifically DHA , may improve literacy and behavior in children with ADHD . The greatest benefit may be observed in children who have comorbid learning difficulties |
13,574 | 28,399,802 | All regimens of interest except INH-9 showed significant benefits in preventing active TB compared to placebo .
Comparisons between active regimens did not reveal significant differences .
While definitions of regimen completion varied across studies , regimens of 3–4 months were associated with a greater likelihood of adequate completion .
Conclusions Most of the active regimens showed an ability to reduce the risk of active TB relative to no treatment , however important differences between active regimens were not found .
Shorter rifamycin-based regimens may offer comparable benefits to longer INH regimens .
Regimens of 3–4 months duration are more likely to be completed than longer regimens | Background We conducted a systematic review and network meta- analysis ( NMA ) to examine the efficacy and completion rates of treatments for latent tuberculosis infection ( LTBI ) .
While a previous review found newer , short- duration regimens to be effective , several included studies did not confirm LTBI , and analyses did not account for variable follow-up or assess completion . | OBJECTIVE To compare the adverse effects and treatment adherence between 2 months of rifampin plus pyrazinamide ( 2RZ ) and 6 months of isoniazid ( 6H ) . BACKGROUND Patients with silicosis in Hong Kong are at high risk of acquiring tuberculosis . A previous study showed that treatment with 6H reduced the risk of silico-tuberculosis by one half . METHOD Patients with silicosis and a Mantoux skin test reaction > or = 10 mm were r and omized to receive either 2RZ or 6H daily . Liver function testing was done monthly during the initial 2 months . The adverse effects and treatment adherence were compared between the two regimens . RESULTS Forty patients ( mean age , 61.6 + /- 9.1 years ) and 36 patients ( mean age , 57.6 + /- 9.7 years ) were r and omized to the 2RZ and 6H arms , respectively ( p > 0.05 ) [ + /- SD ] . Baseline characteristics were comparable . Nineteen patients in the 2RZ arm had peak alanine transaminase ( ALT ) levels > 1.5 times the upper limit of normal ( ULN ) in comparison with only five study subjects of the 6H arm ( 47.5 % vs 13.9 % , p < 0.01 ) . Fourteen patients ( 35 % ) in the 2RZ arm and 1 patient ( 2.8 % ) in the 6H arm had peak ALT levels more than five times the ULN ( p < 0.001 ) . Only seven patients had symptoms suggestive of hepatitis ; none of the patients had jaundice . All recovered after withholding treatment . In the 2RZ study arm , none of the baseline characteristics predicted hepatotoxicity . Other adverse effects were generally mild and comparable between both study arms . Treatment was stopped prematurely in 45 % and 36.1 % of patients in the 2RZ and 6H arms , respectively ( p = 0.43 ) . The main reasons were hepatotoxicity for the 2RZ arm and voluntary withdrawal after experiencing other minor adverse effects for the 6H arm . CONCLUSION A higher incidence of hepatotoxicity was associated with rifampin plus pyrazinamide than isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong Background With the renewed emphasis to implement isoniazid preventive therapy ( IPT ) in Sub-Saharan Africa , we investigated the effect of IPT on immunological profiles among household contacts with latent tuberculosis . Methods Household contacts of confirmed tuberculosis patients were tested for latent tuberculosis using the QuantiFERON ® -TB Gold In-Tube ( QFN ) assay and tuberculin skin test ( TST ) . HIV negative contacts aged above 5 years , positive to both QFN and TST , were r and omly assigned to IPT and monthly visits or monthly visits only . QFN culture supernatants from enrolment and six months ’ follow-up were analysed for M.tb-specific Th1 , Th2 , Th17 , and regulatory cytokines by Luminex assay , and for M.tb-specific IgG antibody concentrations by ELISA . Effects of IPT were assessed as the net cytokine and antibody production at the end of six months . Results Sixteen percent of contacts investigated ( 47/291 ) were r and omised to IPT ( n = 24 ) or no IPT ( n = 23 ) . After adjusting for baseline cytokine or antibody responses , and for presence of a BCG scar , IPT ( compared to no IPT ) result ed in a relative decline in M.tb-specific production of IFN gamma ( adjusted mean difference at the end of six months ( bootstrap 95 % confidence interval ( CI ) , p-value ) -1488.6 pg/ml ( ( −2682.5 , −294.8 ) , p = 0.01 ) , and IL- 2 ( −213.1 pg/ml ( −419.2 , −7.0 ) , p = 0.04 ) . A similar decline was found in anti-CFP-10 antibody levels ( adjusted geometric mean ratio ( bootstrap 95 % CI ) , p-value ) 0.58 ( ( 0.35 , 0.98 ) , p = 0.04 ) . We found no effect on M.tb-specific Th2 or regulatory or Th17 cytokine responses , or on antibody concentrations to PPD and ESAT-6 . Conclusions IPT led to a decrease in Th1 cytokine production , and also in the anti CFP-10 antibody concentration . This could be secondary to a reduction in mycobacterial burden or as a possible direct effect of isoniazid induced T cell apoptosis , and may have implication s for protective immunity following IPT in tuberculosis-endemic countries . Trial registration IS RCT N registry , IS RCT N15705625 . Registered on 30th September 2015 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 BACKGROUND Tuberculosis is epidemic among workers in South African gold mines . We evaluated an intervention to interrupt tuberculosis transmission by means of mass screening that was linked to treatment for active disease or latent infection . METHODS In a cluster-r and omized study , we design ated 15 clusters with 78,744 miners as either intervention clusters ( 40,981 miners in 8 clusters ) or control clusters ( 37,763 miners in 7 clusters ) . In the intervention clusters , all miners were offered tuberculosis screening . If active tuberculosis was diagnosed , they were referred for treatment ; if not , they were offered 9 months of isoniazid preventive therapy . The primary outcome was the cluster-level incidence of tuberculosis during the 12 months after the intervention ended . Secondary outcomes included tuberculosis prevalence at study completion . RESULTS In the intervention clusters , 27,126 miners ( 66.2 % ) underwent screening . Of these miners , 23,659 ( 87.2 % ) started taking isoniazid , and isoniazid was dispensed for 6 months or more to 35 to 79 % of miners , depending on the cluster . The intervention did not reduce the incidence of tuberculosis , with rates of 3.02 per 100 person-years in the intervention clusters and 2.95 per 100 person-years in the control clusters ( rate ratio in the intervention clusters , 1.00 ; 95 % confidence interval [ CI ] , 0.75 to 1.34 ; P=0.98 ; adjusted rate ratio , 0.96 ; 95 % CI , 0.76 to 1.21 ; P=0.71 ) , or the prevalence of tuberculosis ( 2.35 % vs. 2.14 % ; adjusted prevalence ratio , 0.98 ; 95 % CI , 0.65 to 1.48 ; P=0.90 ) . Analysis of the direct effect of isoniazid in 10,909 miners showed a reduced incidence of tuberculosis during treatment ( 1.10 cases per 100 person-years among miners receiving isoniazid vs. 2.91 cases per 100 person-years among controls ; adjusted rate ratio , 0.42 ; 95 % CI , 0.20 to 0.88 ; P=0.03 ) , but there was a subsequent rapid loss of protection . CONCLUSIONS Mass screening and treatment for latent tuberculosis had no significant effect on tuberculosis control in South African gold mines , despite the successful use of isoniazid in preventing tuberculosis during treatment . ( Funded by the Consortium to Respond Effectively to the AIDS TB Epidemic and others ; Thibela TB Current Controlled Trials number , IS RCT N63327174 . ) BACKGROUND A 9-month course of isoniazid monotherapy is currently recommended for the treatment of latent tuberculosis infection ( LTBI ) and has been shown to be effective in both children and adults . Reduced compliance with this regimen has forced physicians to explore shorter regimens . The aim of this study was to compare 3- and 4-month combination regimens of isoniazid plus rifampin with a 9-month regimen of isoniazid monotherapy for the treatment of LTBI in children . METHODS This prospect i ve , r and omized , controlled study was conducted over an 11-year period ( 1995 - 2005 ) . In period 1 ( 1995 - 1998 ) , 232 patients received isoniazid therapy for 9 months ( group A ) , and 238 patients received isoniazid and rifampin for 4 months ( group B ) . In period 2 ( 1999 - 2002 ) , 236 patients were treated with isoniazid and rifampin for 4 months ( group C ) , and 220 patients received the same regimen for 3 months ( group D ) . All patients were observed for > or = 3 years . RESULTS Overall compliance with treatment was good , but patients who received isoniazid monotherapy were less compliant than were those who received short-course combination therapy ( P=.011 , for group A vs. group B ; P=.510 , for group C vs. group D ) . No patient in any group developed clinical disease during the follow-up period . New radiographic findings suggestive of possible active disease were more common in patients who received isoniazid monotherapy ( 24 % ) than in those treated with shorter regimens ( 11.8 % , 13.6 % , and 11 % for groups B , C , and D , respectively ; P=.001 for group A vs. group B ; P=.418 for group C vs. group D ) . Serious drug-related adverse effects were not detected . CONCLUSIONS Short-course treatment with isoniazid and rifampin for 3 - 4 months is safe and seems to be superior to a 9-month course of isoniazid monotherapy INTRODUCTION The aim of this study was to compare the adherence to , and side effects of a 3-month short-course treatment for latent tuberculosis infection as compared to the st and ard 6-month course . METHODS Prospect i ve , comparative , r and omized , open trial including patients with a positive tuberculin skin test and appropriate criteria for treatment in accordance with the CDC guidelines , and excluding patients with HIV infection . Group I ( 6H ) was assigned to isoniazid 300 mg per day for 6 months and Group II ( 3HR ) was assigned to isoniazid 300 mg per day plus rifampin 600 mg per day for 3 months . The patients were followed up for five years . RESULTS A total of 105 patients were included , among which 9 refused treatment ; 45 patients were placed in Group I and 51 patients in Group II . Both groups were comparable at baseline . Hepatotoxicity was 44 % in Group 6H and 29 % in Group 3HR ( P = 0.07 ) . Hepatotoxicity was severe in 6.7 % of Group 6H and 5.8 % of Group 3HR , requiring treatment interruption in 4.4 % and 1.9 % , respectively ( P = NS ) . Among the total , 75.6 % of patients in group 6H , and 90.2 % in group 3HR completed the study treatment ( P = 0.05 ) . Tuberculous disease was detected in only one patient in the 6H group , occurring in the second month of treatment . CONCLUSION In the treatment of latent tuberculosis infection , a 3-month course of isoniazid plus rifampin result ed in better adherence and a lower percentage of discontinued treatments than a 6-month isoniazid course . Tolerance was similar in the two regimens SETTING Nine public health care centres in four Spanish cities . OBJECTIVE To evaluate the efficacy and safety of 2 months of rifampicin ( R ) plus pyrazinamide ( Z ) therapy ( 2RZ ) compared with a 6-month course of isoniazid therapy ( 6H ) for treating latent tuberculosis infection ( LTBI ) . DESIGN Multicentered , r and omised , comparative and prospect i ve trial conducted in HIV-seronegative contacts of infectious pulmonary TB cases . RESULTS Of 352 individuals , 199 received 6H and 153 2RZ ; 73 % of contacts receiving 6H and 71 % receiving 2RZ completed treatment ( P = 0.73 ) . Treatment interruption due to hepatotoxicity ( ALT/AST > 5 times upper limit of normal ) was observed in 10 % of contacts in the 2RZ group and in 2.5 % of the 6H group ( P = 0.007 ) . This higher than expected rate of hepatotoxicity in the 2RZ arm led to premature termination of the study . Severe or fatal liver injury was not detected . Liver function tests normalised after discontinuation of treatment . We conclude that the use of RZ should only be considered when other regimens are unsuitable and intensive monitoring of liver function is feasible There is little published information regarding treatment completion , safety , and efficacy of rifampin administered daily for 4 months-a recommended alternative to 9 months of isoniazid for therapy of latent tuberculosis infection . In an open-label r and omized trial at a university-affiliated respiratory hospital , consenting patients whose treating physician had recommended therapy for latent tuberculosis infection were r and omized to daily self-administered rifampin for 4 months or daily self-administered isoniazid for 9 months . Of 58 patients r and omized to rifampin , 53 ( 91 % ) took 80 % of doses , and 50 ( 86 % ) took more than 90 % of doses within 20 weeks compared with 44 ( 76 % ) and 36 ( 62 % ) who took 80 and 90 % , respectively , of doses of isoniazid within 43 weeks ( relative risks : 80 % of doses , 1.2 [ 95 % confidence interval : 1.02 , 1.4 ] ; 90 % of doses , 1.4 [ 1.1 , 1.7 ] ) . Adverse events result ed in permanent discontinuation of therapy for two ( 3 % ) patients taking rifampin , and for eight ( 14 % ) patients taking isoniazid . Three patients developed drug-induced hepatitis -- all were taking isoniazid . Total costs of therapy were significantly higher for isoniazid . In conclusion , completion of therapy was significantly better with 4 months of rifampin and major side effects were somewhat lower . Further studies are needed to assess the safety and efficacy of the 4-month rifampin regimen A controlled and double-blind study to determine the efficacy of isoniazid in preventing the development of pulmonary tuberculosis among the household contacts of open cases of the disease has been carried out in a rural area of Kenya-a financially h and icapped country-under realistic field conditions . A one-year course of isoniazid ( 5 - 10 mg per kg of body-weight in one daily dose ) administered to the contacts of active cases gave a reduction in respect of the excretion of tubercle bacilli of the order of 90 % at the end of the year . In the subsequent observation period ( 2 - 4 years ) both the control and the isoniazid-treated group showed a low and similar rate of adverse findings .Previous studies by the Tuberculosis Chemotherapy and BCG Centre , Nairobi , had revealed that the risk of tuberculosis among household contacts , especially children , was high and , further , that the acceptability of the drug and the regularity of drug-taking were poor among these contacts . Even so , a very considerable prophylactic effect of isoniazid was demonstrated in the present study . It therefore seems justifiable to conclude that the treatment of household contacts with isoniazid could contribute to tuberculosis control in financially h and icapped countries , particularly where a tuberculosis case-finding programme is reasonably well established Background Treatment of latent infection is needed to protect HIV-infected individuals against tuberculosis . A previous report addressed short-term efficacy of three regimens in HIV-infected adults . We now report on long-term efficacy of the study regimens . Methods Three daily self-administered regimens were compared in a r and omized placebo-controlled trial in 2736 purified protein derivative (PPD)-positive and anergic HIV-infected adults . PPD-positive subjects were treated with isoniazid ( INH ) for 6 months ( 6H ) , INH plus rifampicin for 3 months ( 3HR ) , INH plus rifampicin and pyrazinamide for 3 months ( 3HRZ ) , or placebo for 6 months . Anergic subjects were r and omized to 6H or placebo . Results 6H initially protected against tuberculosis in PPD-positive individuals ; however , benefit was lost within the first year of treatment . Sustained benefit was observed in persons receiving 3HR and 3HRZ . In a Cox regression analysis , the adjusted relative risk for tuberculosis compared with placebo was 0.67 [ 95 % confidence interval ( CI ) , 0.42–1.07 ] for 6H , 0.49 ( 95 % CI , 0.29–0.82 ) for 3HR , and 0.41 ( 95 % CI , 0.22 - 0.76 ) for 3HRZ . When the rifampicin-containing regimens were combined , the adjusted relative risk for tuberculosis compared with placebo was 0.46 ( 95 % CI , 0.29–0.71 ) . Among anergic subjects , a modest degree of protection with 6H was present ( adjusted relative risk , 0.61 ; 95 % CI , 0.32–1.16 ) . Treatment of latent tuberculosis infection had no effect on mortality . ConclusionS ix months of INH provided short-term protection against tuberculosis in PPD-positive HIV-infected adults . Three month regimens including INH plus rifampicin or INH , rifampicin and pyrazinamide provided sustained protection for up to 3 years RATIONALE Treatment of latent tuberculosis ( TB ) infection with weekly rifapentine and isoniazid is a potentially effective alternative to current therapies . OBJECTIVES To compare the efficacy of weekly rifapentine/isoniazid to daily rifampin/pyrazinamide in preventing TB in household contacts of patients with pulmonary TB in Brazil . METHODS Contacts of patients with TB were r and omized to rifapentine 900 mg/isoniazid 900 mg once weekly for 12 wk or rifampin 450 - 600 mg/pyrazinamide 750 - 1,500 mg daily for 8 wk and followed for at least 2 yr . MEASUREMENTS TB rates , adverse events , and adherence to therapy . MAIN RESULTS A total of 399 household contacts were enrolled , 206 in the rifapentine/isoniazid arm and 193 in the rifampin/pyrazinamide arm . The median age was 34 yr , median weight was 63 kg , 60 % of participants were female , and only one patient was HIV infected . Rifapentine/isoniazid was well tolerated , but the trial was halted by the investigators before completion because of unanticipated hepatotoxicity in the rifampin/pyrazinamide arm . Twenty of 193 participants ( 10 % ) receiving rifampin/pyrazinamide experienced grade 3 or 4 hepatotoxicity , compared with 2 of 206 participants ( 1 % ) on rifapentine/isoniazid ( p<0.001 ) . There were no hospitalizations or deaths due to hepatotoxicity , and all participants ' liver enzyme levels returned to normal during follow-up . During follow-up , four cases of active TB developed , three in the rifapentine/isoniazid group and one in the rifampin/pyrazinamide group ( 1.46 vs. 0.52 % ; difference , 0.94 % ; 95 % confidence interval , -1.6 to 3.7 % ) . CONCLUSIONS Rifapentine/isoniazid was better tolerated than rifampin/pyrazinamide and was associated with good protection against TB . Rifapentine/isoniazid weekly for 12 wk is likely a promising therapy for latent TB infection BACKGROUND We performed a r and omized trial of isoniazid treatment based on interferon-γ-releasing assay ( IGRA ) in kidney transplant ( KT ) recipients in an intermediate-TB-burden country . METHODS All adult patients admitted to a KT institute between June 2010 and May 2013 were enrolled . The IGRA ( T-SPOT.TB assay ) was performed on all patients , and isoniazid treatment was given to those with clinical risk factors for latent TB infection ( LTBI ) . Patients with positive IGRA who had no clinical risk factors for LTBI were r and omly assigned to isoniazid treatment or a control group . The development of TB after KT was monitored between June 2010 and November 2013 . The primary endpoint was the development of TB . RESULTS Of the 784 patients who had no clinical risk factors for LTBI , 445 ( 57 % ) gave negative results in the IGRA , 76 ( 10 % ) indeterminate results and 263 ( 33 % ) positive results . Of the latter , 131 were allocated to isoniazid treatment and 132 to the control group . Three ( 2 % ) of the control group developed TB , whereas none of the isoniazid treatment group developed TB ( rate difference 1.22 per 100 person-years , P = 0.09 ) . Of the 521 patients with negative or indeterminate IGRA results , 4 [ 0.8 % , 0.43 per 100 person-years ( 95 % CI 0.12 - 1.09 ) ] developed TB after KT . CONCLUSIONS IGRA-based isoniazid treatment has a trend towards reducing TB development in KT recipients without clinical risk factors , but careful monitoring of TB development is needed in negative-IGRA KT recipients BACKGROUND Tuberculosis is a common complication of HIV-1 infection , especially in developing countries . Practical and effective chemoprophylaxis regimens for HIV-1-related tuberculosis are needed . Our aim was to test the efficacy of isoniazid versus rifampicin with pyrazinamide for prevention of tuberculosis in HIV-1-positive individuals . METHODS We compared the efficacy of 6 months of isoniazid with 2 months of rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1-seropositive individuals . Eligible participants were aged 16 - 77 years , HIV-1 seropositive , had a positive purified-protein derivative ( PPD ) skin test reaction of at least 5 mm , and had a normal chest radiograph . Participants were r and omly assigned partially supervised twice weekly isoniazid for 24 weeks or twice weekly rifampicin and pyrazinamide for 8 weeks . Participants were followed up for up to 4 years for the development of tuberculosis and survival . FINDINGS Tuberculosis developed in 14 ( 3.8 % ) of 370 participants assigned isoniazid and 19 ( 5.0 % ) of 380 participants assigned rifampicin and pyrazinamide ( Cox model rate ratio 1.3 [ 95 % CI 0.7 - 2.7 ] ) . The Kaplan-Meier estimate of the risk of tuberculosis during the first 10 months after entry was 3.7 % among participants who received rifampicin and pyrazinamide compared with 1.0 % ( p=0.03 ) among participants who received isoniazid , and 5.4 % versus 5.1 % , respectively ( p=0.9 ) at 36 months after entry . Higher rates of tuberculosis were observed in people with baseline CD4 percentages ( of total lymphocytes ) of less than 20 ( rate ratio 4.0 [ 95 % CI 1.8 - 9.0 ] ) . There were no significant differences in total mortality at any time . INTERPRETATION Twice-weekly isoniazid preventive therapy for 6 months or rifampicin and pyrazinamide for 2 months provided similar overall protection against tuberculosis in HIV-1-infected , PPD-positive adults . The better protection among recipients of isoniazid during the first 10 months was most likely secondary to the longer duration of chemoprophylaxis . Preventive therapy for HIV-1-seropositive , PPD-positive individuals could be practical in developing countries with a once weekly clinic visit , but optimum duration of chemoprophylaxis has not been determined SETTING R and omised controlled trial of latent tuberculosis infection ( LTBI ) treatment in 10 clinics in Canada , Saudi Arabia and Brazil . OBJECTIVE To identify early predictors of LTBI treatment adherence , including pre-treatment characteristics . DESIGN Patients r and omised to 4 months of rifampicin ( RMP ; n = 420 ) or 9 months of isoniazid ( n = 427 ) were monitored for adherence using an electronic device . Outcomes were 1 ) treatment completion , defined as intake of > or=80 % of the prescribed doses , and further categorised as completed within the allotted time or not ; and 2 ) treatment regularity , measured by the time interval between doses . Relative risk ( RR ) and adjusted odds ratios ( aOR ) of patients ' pre-treatment characteristics and adherence at first follow-up visit were calculated . RESULTS Completion of treatment was higher with RMP ( aOR 4.3 , 95%CI 2.7 - 6.8 ) . Early predictors ( first follow-up visit ) of non-adherence were late first visit attendance ( RR for completion in time 0.9 , 95%CI 0.8 - 0.98 ) , > 20 % of missed doses ( RR 0.4 , 95%CI 0.3 - 0.6 ) and greater variation of hours between doses ( 0.209 vs. 0.131 , P < 0.001 ) . Serious adverse events were not associated with irregularity of treatment . CONCLUSION The shorter RMP regimen was associated with better adherence . Patients with poor adherence could be identified at the first follow-up visit from their punctuality in follow-up , missed doses and variability of pill-taking SETTING A prison in northern Taiwan . OBJECTIVE To compare safety and the completion rate of the 4-month daily rifampicin regimen ( 4R ) vs. the st and ard 6-month daily isoniazid regimen ( 6H ) for latent tuberculosis infection ( LTBI ) in prison inmates . DESIGN This was an open-label r and omised trial among human immunodeficiency virus negative male inmates . Inmates without active tuberculosis ( TB ) who tested positive for both the tuberculin skin test and QuantiFERON ® -TB Gold In-Tube were eligible , but those with baseline glutamic pyruvic transaminase ( GPT ) levels ≥ 120 U/l , bilirubin levels ≥ 2.4 U/l or a platelet count < 150 k/mm(3 ) were excluded . The primary endpoint was any adverse event that result ed in discontinuation of LTBI treatment . RESULTS Participants ( n = 373 ; 14 % hepatitis B surface antigen positive , 21 % anti-hepatitis C virus [ HCV ] positive ) were r and omised ( stratified by hepatitis B virus , HCV status and 2-year prison term ) to receive either 4R or 6H under directly observed treatment . The 4R group ( n = 190 ) was less likely to experience an adverse event leading to discontinuation of treatment ( 2 % vs. 12 % , P < 0.001 for all adverse events ; 0 % vs. 8 % , P < 0.001 for hepatotoxicity ) , and more likely to complete LTBI treatment ( 86 % vs. 78 % , P = 0.041 ) , compared with the 6H group ( n = 183 ) . CONCLUSIONS 4R is safer and has a higher completion rate than 6H as treatment for LTBI among male prison inmates OBJECTIVES To compare the tolerance , adherence and effectiveness of two approaches for the treatment of latent tuberculosis infection ( LTBI ) : 6 months of isoniazid ( 6H ) vs. 3 months of isoniazid plus rifampicin ( 3RH ) . POPULATION Immigrants with LTBI . METHODS Participants were enrolled in a controlled , r and omised clinical trial in Barcelona , Spain , from April 2001 to April 2005 . Monthly follow-up was done to assess tolerance , side effects and adherence . Effectiveness was evaluated at 5 years . RESULTS In the 590 subjects enrolled , the rate of adherence was greater in the 3RH than in the 6H arm ( 72 % vs. 52.4 % , P = 0.001 ) . No differences between study arms were observed with respect to hepatotoxicity or side effects . Variables associated with non-adherence were diagnosis by screening ( OR 1.88 , 95%CI 1.26 - 2.82 , P = 0.001 ) , illegal immigration status ( OR 1.48 , 95%CI 1.01 - 2.15 , P = 0.03 ) , unemployment ( OR 1.91 , 95%CI 1.28 - 2.85 , P = 0.0008 ) , illiteracy ( OR 1.73 , 95%CI 1.04 - 2.88 , P = 0.02 ) , lack of family support ( OR 3.7 , 95%CI 2.54 - 5.4 , P = 0.001 ) and the 6-month treatment regimen ( OR 2.45 , 95%CI 1.68 - 3.57 , P = 0.0001 ) . None of the patients who completed either treatment developed tuberculosis . CONCLUSIONS The 3RH regimen facilitates adherence to LTBI treatment and offers a safe , well-tolerated and effective alternative A total of 28 000 persons with fibrotic pulmonary lesions compatible with tuberculosis were followed for five years after receiving 12 , 24 , or 52 weeks of preventive treatment with isoniazid or placebo . Compared with placebo , 12 weeks of isoniazid eliminated less than one-third , and 24 weeks eliminated two-thirds of the tuberculosis risk . Where preventive treatment is not currently practised , adopting a 24-week regimen could decrease the incidence of tuberculosis in such population s by 65%.Hepatitis , the only serious side-effect encountered , occurred infrequently but was more common among isoniazid recipients ( 0.5 % ) than among placebo recipients (0.1%).Fifty-two weeks of isoniazid prevented the most tuberculosis , but 24 weeks prevented more tuberculosis cases per case of hepatitis caused . Where preventive treatment is currently practised for 52 weeks , adopting a 24-week regimen would decrease hepatitis by one-third and increase tuberculosis by 40 % BACKGROUND AND OBJECTIVE We aim ed to compare treatment adherence and toxicity of isoniazide ( H ) ( 6 months ) compared with rifampicine ( R ) + pirazinamide ( Z ) ( 2 months ) in homeless patients in latent tuberculous infection ( LTBI ) . PATIENTS AND METHOD R and omized and controlled prospect i ve study . RESULTS We included 172 patients ( 116 males and 56 females ) with an age average of 42.3 ( 12.8 ) years ; 31 ( 18 % ) had recent conversion and 72 ( 41.8 % ) had some risk factor of hepatotoxicity . Both bivariate and multivariate analysis ( p < 0.001 ; OR = 5.15 [ 2.34 - 11.35 ] ) showed that the treatment was completed by 61.5 % of patients administered the R+Z regimen , while it was completed only by 28.2 % of those administered H for 6 months . Moreover , treatment was completed by 48.4 % of Spanish or foreign patients with legal residence , while it was completed only by 28.6 % of immigrant patients with no legal residence ( p = 0.044 in bivariate analysis ) . CONCLUSIONS The R+Z regimen for 2 months as treatment of LTBI in homeless patients displays a higher adherence than H for 6 months . There were no differences in toxicity IMPORTANCE Three months of a once-weekly combination of rifapentine and isoniazid for treatment of latent tuberculosis infection is safe and effective for persons 12 years or older . Published data for children are limited . OBJECTIVES To compare treatment safety and assess noninferiority treatment effectiveness of combination therapy with rifapentine and isoniazid vs 9 months of isoniazid treatment for latent tuberculosis infection in children . DESIGN , SETTING , AND PARTICIPANTS A pediatric cohort nested within a r and omized , open-label clinical trial conducted from June 11 , 2001 , through December 17 , 2010 , with follow-up through September 5 , 2013 , in 29 study sites in the United States , Canada , Brazil , Hong Kong ( China ) , and Spain . Participants were children ( aged 2 - 17 years ) who were eligible for treatment of latent tuberculosis infection . INTERVENTIONS Twelve once-weekly doses of the combination drugs , given with supervision by a health care professional , for 3 months vs 270 daily doses of isoniazid , without supervision by a health care professional , for 9 months . MAIN OUTCOMES AND MEASURES We compared rates of treatment discontinuation because of adverse events ( AEs ) , toxicity grade s 1 to 4 , and deaths from any cause . The equivalence margin for the comparison of AE-related discontinuation rates was 5 % . Tuberculosis disease diagnosed within 33 months of enrollment was the main end point for testing effectiveness . The noninferiority margin was 0.75 % . RESULTS Of 1058 children enrolled , 905 were eligible for evaluation of effectiveness . Of 471 in the combination-therapy group , 415 ( 88.1 % ) completed treatment vs 351 of 434 ( 80.9 % ) in the isoniazid-only group ( P = .003 ) . The 95 % CI for the difference in rates of discontinuation attributed to an AE was -2.6 to 0.1 , which was within the equivalence range . In the safety population , 3 of 539 participants ( 0.6 % ) who took the combination drugs had a grade 3 AE vs 1 of 493 ( 0.2 % ) who received isoniazid only . Neither arm had any hepatotoxicity , grade 4 AEs , or treatment-attributed death . None of the 471 in the combination-therapy group developed tuberculosis vs 3 of 434 ( cumulative rate , 0.74 % ) in the isoniazid-only group , for a difference of -0.74 % and an upper bound of the 95 % CI of the difference of + 0.32 % , which met the noninferiority criterion . CONCLUSIONS AND RELEVANCE Treatment with the combination of rifapentine and isoniazid was as effective as isoniazid-only treatment for the prevention of tuberculosis in children aged 2 to 17 years . The combination-therapy group had a higher treatment completion rate than did the isoniazid-only group and was safe . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00023452 SETTING A medical facility for approximately 90,000 gold miners employed on 24 South African gold mines . OBJECTIVE To evaluate the effectiveness of rifampicin , isoniazid and pyrazinamide given for 3 months for the prevention of tuberculosis in men with silicosis . DESIGN A r and omised double-blind placebo controlled trial with active 4-year follow up of subjects by routine radiographic screening . RESULTS A total of 382 gold miners with silicosis were r and omised to receive rifampicin 600 mg , isoniazid 400 mg and pyrazinamide 1.25 g daily as Rifater or a placebo . These men have been followed for 4 years since the end of the treatment period . Eleven men who received the combination tablet and 15 men who received the placebo tablet have developed tuberculosis ( chi 2 df1 = 0.66 , P = 0.4 ) . CONCLUSION This multi-drug short course chemoprophylaxis regimen has failed to prevent tuberculosis in miners with silicosis . Even if a larger study had demonstrated a statistically significant effect of the regimen as compared with placebo , the rate of tuberculosis in the men who received the three-drug regimen was unacceptably high BACKGROUND Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination . The current st and ard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion . METHODS We conducted an open-label , r and omized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine ( 900 mg ) plus isoniazid ( 900 mg ) ( combination-therapy group ) with 9 months of self-administered daily isoniazid ( 300 mg ) ( isoniazid-only group ) in subjects at high risk for tuberculosis . Subjects were enrolled from the United States , Canada , Brazil , and Spain and followed for 33 months . The primary end point was confirmed tuberculosis , and the noninferiority margin was 0.75 % . RESULTS In the modified intention-to-treat analysis , tuberculosis developed in 7 of 3986 subjects in the combination-therapy group ( cumulative rate , 0.19 % ) and in 15 of 3745 subjects in the isoniazid-only group ( cumulative rate , 0.43 % ) , for a difference of 0.24 percentage points . Rates of treatment completion were 82.1 % in the combination-therapy group and 69.0 % in the isoniazid-only group ( P<0.001 ) . Rates of permanent drug discontinuation owing to an adverse event were 4.9 % in the combination-therapy group and 3.7 % in the isoniazid-only group ( P=0.009 ) . Rates of investigator-assessed drug-related hepatotoxicity were 0.4 % and 2.7 % , respectively ( P<0.001 ) . CONCLUSIONS The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate . Long-term safety monitoring will be important . ( Funded by the Centers for Disease Control and Prevention ; PREVENT TB Clinical Trials.gov number , NCT00023452 . ) Context Isoniazid is hepatotoxic and must be taken for 9 months by patients with latent tuberculosis infection . Contribution In this trial comparing 4 months of rifampin therapy with 9 months of isoniazid therapy , patients who took rifampin had fewer adverse events and were more likely to complete treatment . Caution The investigators did not compare efficacy of the 2 treatments . Implication These safety and adherence data justify a larger trial to compare the efficacy of rifampin and isoniazid for latent tuberculosis infection . The Editors After detection and treatment of active tuberculosis cases , the next priority in tuberculosis control is the diagnosis and treatment of persons with latent tuberculosis infection ( LTBI ) who are at increased risk for active tuberculosis . Treatment of such individuals can provide individual and public health benefits ( 14 ) . The current recommended st and ard therapy in most countries is 9 months of isoniazid therapy ( 4 , 5 ) . The drug has more than 90 % efficacy if taken the entire 9 months ( 6 ) , but completion rates under routine practice conditions are about 50 % or less ( 79 ) . Another important disadvantage of isoniazid therapy is the occurrence of serious adverse events , particularly drug-induced hepatitis ( 10 ) . Drug-induced hepatitis was not recognized as a complication of isoniazid therapy in early trials involving more than 50000 participants ( 11 ) , but it was a frequent and potentially severe problem after isoniazid was recommended for tuberculosis prevention in 1970 ( 12 ) and was subsequently used more widely ( 13 , 14 ) . This complication makes close monitoring necessary , increasing costs . These problems have stimulated considerable interest in finding shorter and safer regimens for the treatment of LTBI ( 15 ) . One alternative , 2 months of daily rifampinpyrazinamide , was recommended in 2000 ( 4 ) on the basis of evidence from several trials ( 1618 ) . However , subsequent reports of severe and fatal hepatotoxicity ( 19 , 20 ) have rendered this regimen unacceptable for most patients . The remaining recommended alternative is 4 months of daily rifampin , but published outcome information is limited and systematic review s on this regimen have not been done . In the only published trial that compared 3 months of daily rifampin therapy with 6 months of daily isoniazid therapy in 332 patients , efficacy and safety were similar ( 21 ) . In 2 uncontrolled case series , 6 months of daily rifampin was well tolerated in 49 homeless persons in Boston ( 22 ) and in 157 high school students in California ( 23 ) . Two nonr and omized studies have described better treatment completion and less hepatotoxicity with 4 months of rifampin than with 9 months of isoniazid under program conditions ( 8 , 9 ) . However , rifampin has been reported to cause other problemsnotably drug interactions ( 24 ) , a flu-like syndrome ( 24 ) , and rare hematologic problems ( immune-mediated thrombocytopenia and anemia ) ( 25 ) . Also , development of drug resistance is a theoretical concern . Given the experience with isoniazid and 2 months of rifampinpyrazinamide , both of which were thought to be safe on the basis of early studies but caused deaths when used more widely , we design ed a multicenter , r and omized trial to compare the frequency of serious adverse events and treatment completion rates in patients given 4 months of daily rifampin or 9 months of daily isoniazid for LTBI . Methods Setting , Study Sample , and R and omization This open-label trial was conducted at 9 university-affiliated hospitals : 7 in Canada and 1 each in Saudi Arabia and Brazil . We considered patients to be eligible if they were age 18 years or older and had a documented tuberculin skin test that met the criteria for a positive result ( 5 ) and if their primary treating physician initially recommended isoniazid for LTBI following national or international guidelines ( 4 , 26 , 27 ) . Patients were ineligible if they were contacts of isoniazid- or rifampin-resistant cases ( 28 ) , were allergic to isoniazid or rifamycins , or were taking concomitant medications that had clinical ly significant potential drug interactions that could not be easily managed . To ensure a realistic assessment of adverse events , we considered all other adults eligible , regardless of age or additional risk factors for adverse events , as long as their treating physician felt that therapy for LTBI was indicated . A Web-based program verified eligibility and r and omly assigned participants ( by using a r and om-number generator ) , after they signed informed consent , to 4 months of daily rifampin ( 10 mg per kg of body weight , up to 600 mg/d ) or 9 months of daily isoniazid ( 5 mg/kg , up to 300 mg/d ) in blocks of varying size , stratified by center . A team at the University of Sherbrooke , Sherbrooke , Quebec , Canada , prepared the Web-based program and allocation sequence . Study personnel in the different centers enrolled and registered participants , obtained consent , verified assignment , and administered treatment . All study participants signed informed consent before r and omization . Institutional review boards in each participating institution approved the study . Processes and Outcomes Patients were followed in routine fashion by their usual treating physician , who made all management decisions , including discontinuation of therapy . By study protocol , all patients had blood tests ( complete blood count , liver aminotransferase levels [ aspartate aminotransferase and alanine aminotransferase ] , and bilirubin level ) before and after 1 and 2 months of therapy and were seen every month for the first 4 months of therapy and ( for those receiving 9 months of isoniazid ) at physician discretion every 6 weeks thereafter . Adverse events could be detected at any time throughout the course of therapy . When the treating physician suspected an adverse event and therapy was suspended , investigations , including blood tests , were performed according to study protocol . The treating physician decided whether to discontinue , rechallenge with , or restart the study therapy , although the protocol specified that participants with grade 3 or 4 adverse events ( Appendix Table 1 ) were not to be rechallenged . When all investigations were complete , and if therapy was permanently discontinued in response to the event , the patient 's clinical course and results of investigations and rechallenge ( if any ) were made available to a 3-member independent review panel who were blinded to study drug . If therapy was resumed ( for example , after resolution of a grade 1 or 2 adverse event ) and the event did not recur , the patient 's information was not review ed by the panel . Appendix Table 1 . Grading System for Adverse Events Used by Independent Panel Each review panel member had substantial experience and expertise in clinical and epidemiologic aspects of tuberculosis , and each independently judged the type and severity of the adverse events and its likely relationship to the study drug . We grade d adverse events as recommended by the National Cancer Institute Common Terminology Criteria for Adverse Events , version 2.0 ( 29 ) ( Appendix Table 1 ) . Liver aminotransferase levels that increased to 5 to 10 or 3 to 10 times the upper limit of normal in the presence of compatible symptoms met criteria for grade 3 hepatotoxicity , whereas those that exceeded 10 times the upper limit of normal met criteria for grade 4 toxicity ( 30 ) . In the event of disagreement , panel members re- review ed the information ; if disagreement remained , the majority opinion was used . The study 's primary outcome was the frequency of grade 3 or 4 adverse events that result ed in study drug discontinuation and were judged by the review panel to be probably related to the drug ( Appendix Table 1 ) . The study 's secondary outcome was on-time treatment completion , defined as taking more than 80 % of doses within a maximum of 150 days for 4 months of rifampin or 301 days ( 43 weeks ) for 9 months of isoniazid . Doses taken were measured with the Medical Event Monitoring System , an electronic device in the pill container cap that recorded the date and time of bottle opening ( APREX Corporation , Fremont , California ) . Other secondary outcomes included grade 1 or 2 adverse events that were judged by the independent panel to be probably study drugrelated and result ed in permanent discontinuation of therapy and changes in liver aminotransferase levels and leukocyte and platelet counts before and 1 and 2 months after beginning treatment . Statistical Analysis We initially calculated a trial sample size by assuming that the frequency of serious adverse events would be significantly higher with rifampin . We calculated that 630 patients per group would provide 90 % power ( 2-sided = 0.05 ) to detect a difference between frequency of adverse events of 9 % and 4 % in the rifampin and isoniazid groups , respectively . This estimate also accounted for an anticipated 15 % dropout rate during therapy . Because we were unsure about the actual frequency of adverse events with rifampin , we also noted that 630 patients per group provided 80 % power to detect a statistically significant difference between rates of adverse events in the 2 groups if the event rates were 2 % and 5 % in the rifampin and isoniazid groups , respectively , and the dropout rate was 15 % . To ensure safety of study participants , we planned 3 interim analyses for when 25 % , 50 % , and 75 % of the planned total sample size had been r and omly assigned . The data safety and monitoring board , blinded to the identity of the 2 groups , review ed the overall rate of serious adverse events in each group . If the rate was significantly higher in 1 group , then the results were unblinded and the data safety and monitoring board made a decision , based on clinical judgment and statistical input , about stopping or continuing the trial . We used an value of 0.01 to account for multiple testing ( 31 ) . We reported summary baseline liver function test results for each group as the ratio of each patient 's test result to the upper The tolerability of and adherence to intermittent short-term rifabutin-isoniazid preventive treatment was assessed in subjects dually infected with Mycobacterium tuberculosis and the human immunodeficiency virus ( HIV ) . In a r and omised , open-label , phase II pilot study , 44 subjects received either rifabutin 300 mg and isoniazid 750 mg twice weekly for 3 months ( group A , n = 16 ) or the same regimen with rifabutin at 600 mg ( group B , n = 14 ) , or isoniazid 300 mg/day for 6 months ( group C , n = 14 ) . Three , two and four subjects in groups A , B , and C , respectively , did not complete their treatment ( one case of flu-like syndrome in group B ; one methadone withdrawal syndrome in group A ; and patient decision in two cases in group A and four in group C ) . Overall , adverse events were reported by four , nine , and seven subjects in groups A , B and C , respectively . Intermittent combined rifabutin + isoniazid for 3 months had lower default rates than daily st and ard isoniazid for 6 months . The regimen with rifabutin at 300 mg dose compared favourably to st and ard isoniazid , and warrants larger efficacy studies to assess its role for the prevention of latent tuberculosis in HIV-infected subjects INTRODUCTION To compare compliance with two isoniazid regimens in drug users with latent tuberculosis infection . METHODS . DESIGN clinical trial . Group 1 : isoniazid 300 mg once daily ( 16 patients ) ; Group 2 : isoniazid 900 mg/twice weekly ( 21 ) . ENDPOINTS compliance , toxicity and efficacy . RESULTS Group 1 vs. Group 2 : continuation in program 81/82 % ( p 5 NS ) , compliance full doses 43.7/66.6 % ( p 5 0.1 ) , median percentage of days not taking isoniazid : 1.8 ( 0.2 - 4.3 ) vs. 0 ( 0 - 1.7 ) ( p 5 0.06 ) . CONCLUSIONS Compliance was high in both therapeutic arms . The twice-weekly isoniazid regimen favored compliance , but differences were not significant BACKGROUND Treatment of latent tuberculosis in patients infected with the human immunodeficiency virus ( HIV ) is efficacious , but few patients around the world receive such treatment . We evaluated three new regimens for latent tuberculosis that may be more potent and durable than st and ard isoniazid treatment . METHODS We r and omly assigned South African adults with HIV infection and a positive tuberculin skin test who were not taking antiretroviral therapy to receive rifapentine ( 900 mg ) plus isoniazid ( 900 mg ) weekly for 12 weeks , rifampin ( 600 mg ) plus isoniazid ( 900 mg ) twice weekly for 12 weeks , isoniazid ( 300 mg ) daily for up to 6 years ( continuous isoniazid ) , or isoniazid ( 300 mg ) daily for 6 months ( control group ) . The primary end point was tuberculosis-free survival . RESULTS The 1148 patients had a median age of 30 years and a median CD4 cell count of 484 per cubic millimeter . Incidence rates of active tuberculosis or death were 3.1 per 100 person-years in the rifapentine-isoniazid group , 2.9 per 100 person-years in the rifampin-isoniazid group , and 2.7 per 100 person-years in the continuous-isoniazid group , as compared with 3.6 per 100 person-years in the control group ( P>0.05 for all comparisons ) . Serious adverse reactions were more common in the continuous-isoniazid group ( 18.4 per 100 person-years ) than in the other treatment groups ( 8.7 to 15.4 per 100 person-years ) . Two of 58 isolates of Mycobacterium tuberculosis ( 3.4 % ) were found to have multidrug resistance . CONCLUSIONS On the basis of the expected rates of tuberculosis in this population of HIV-infected adults , all secondary prophylactic regimens were effective . Neither a 3-month course of intermittent rifapentine or rifampin with isoniazid nor continuous isoniazid was superior to 6 months of isoniazid . ( Funded by the National Institute of Allergy and Infectious Diseases and others ; Clinical Trials.gov number , NCT00057122 . ) |
13,575 | 27,153,832 | Results The comprehensive needs assessment highlighted key barriers to PSB , such as knowledge , skills , self-efficacy , routine setting and behaviour regulation and underlined the importance of individual , social and structural influences .
Parenting skills ( routine setting and the ability to manage the behaviour of a reluctant child ) were emphasised as critical to the success of PSB .
IM , although a time-consuming process , allowed us to capture this complexity and allowed us to develop two community-based intervention pathways covering both universal and targeted approaches , which can be integrated into current provision . | Background Dental caries in young children is a major public health problem impacting on the child and their family in terms of pain , infection and substantial financial burden on healthcare funders .
In the UK , national guidance on the prevention of dental caries advises parents to supervise their child ’s brushing with fluoride toothpaste until age 7 .
However , there is a dearth of evidence -based interventions to encourage this practice in parents .
The current study used intervention mapping ( IM ) to develop a home-based parental-supervised toothbrushing intervention to reduce dental caries in young children . | Background The workplace is an ideal setting for health promotion . Helping employees to be more physically active can not only improve their physical and mental health , but can also have economic benefits such as reduced sickness absence . The current paper describes the development of a three month theory-based intervention that aims to increase levels of moderate intensity physical activity amongst employees in sedentary occupations . Methods The intervention was developed using an intervention mapping protocol . The intervention was also informed by previous literature , qualitative focus groups , an expert steering group , and feedback from key contacts within a range of organisations . Results The intervention was design ed to target awareness ( e.g. provision of information ) , motivation ( e.g. goal setting , social support ) and environment ( e.g. management support ) and to address behavioural ( e.g. increasing moderate physical activity in work ) and interpersonal outcomes ( e.g. encourage colleagues to be more physically active ) . The intervention can be implemented by local facilitators without the requirement for a large investment of re sources . A facilitator manual was developed which listed step by step instructions on how to implement each component along with a suggested timetable . Conclusion Although time consuming , intervention mapping was found to be a useful tool for developing a theory based intervention . The length of this process has implication s for the way in which funding bodies allow for the development of interventions as part of their funding policy . The intervention will be evaluated in a cluster r and omised trial involving 1350 employees from 5 different organisations , results available September 2009 1 The AAPD encourages oral health care providers and caregivers to implement 17 simple preventive practice s that can decrease a childs risks of developing this devastating disease . 18 19 20 21 Methods This policy revision is based on a review of the current pediatric dental , medical , and public health literature related to ECC , including 22 the proceedings of the 2005 Symposium on the Prevention of Oral Disease in Children and Adolescents , Chicago , Illinois1997 Conference on Early Childhood Caries , Bethesda , Md.1 A MEDLINE search was conducted using the terms early childhood caries , nursing caries , and baby bottle caries. 25 The literature includes studies that used sound scientific methodology , were reported in refereed journals , and are accepted by the dental profession as state of the art in caries causes and prevention . The literature on the consequences of ECC is based on both prospect i ve and retrospective clinical studies that followed accepted clinical protocol s. Preventive recommendations were based primarily upon review of published studies and proceedings . In cases where the data did not appear sufficient or were inconclusive , recommendations were based upon expert and consensus opinion . 23 Scottish children have one of the highest levels of caries experience in Europe . Only 33 % of 5-year-old children in Dundee who developed caries in their first permanent molars by 7 brushed their teeth twice a day . High-caries-risk children should benefit if they brush more often with fluori date d toothpaste . The aim of this clinical trial was to determine the reduction in 2-year caries increment that can be achieved by daily supervised toothbrushing on school-days with a toothpaste containing 1,000 ppm fluoride ( as sodium monofluorophosphate ) and 0.13 % calcium glycerophosphate , combined with recommended daily home use , compared to a control group involving no intervention other than 6-monthly clinical examinations . Five hundred and thirty-four children , mean age 5.3 , in schools in deprived areas of Tayside were recruited . Each school had two parallel classes , one r and omly selected to be the brushing class and the other , the control . Local mothers were trained as toothbrushing supervisors . Children brushed on school-days and received home supplies . A single examiner undertook 6-monthly examinations recording plaque , caries ( D1 level ) , and used FOTI to supplement the visual caries examination . For children in the brushing classes , the 2-year mean caries increment on first permanent molars was 0.81 at D1 and 0.21 at D3 compared to 1.19 and 0.48 for children in the control classes ( significant reductions of 32 % at D1 and 56 % at D3 ) . In conclusion , high-caries-risk children have been shown to have significantly less caries after participating in a supervised toothbrushing programme with a fluori date d toothpaste The purpose of this study was to describe oral hygiene factors in infants and toddlers living in Sweden with special reference to caries prevalence at 2 and 3 yr of age and to immigrant status . The study was design ed as a prospect i ve , longitudinal study starting with 671 children aged 1 yr . At 3 yr , all the children were invited to a further examination . A total of 298 children , r and omly selected from the original group , were also examined at 2 yr . The accompanying parent was interviewed about the child 's oral health habits . Children who were free of caries at 3 yr had had their teeth brushed more frequently at 1 and 2 yr of age , had used fluoride (F)-toothpaste more often at 2 yr of age , and had a lower prevalence of visible plaque at 1 and 2 yr of age than children with caries . Immigrant children had had their teeth brushed less frequently , had used less F-toothpaste , and had a higher prevalence of visible plaque at 1 yr of age than nonimmigrant children . Early establishment of good oral hygiene habits and regular use of F-toothpaste seem to be important for achieving good oral health in pre-schoolchildren |
13,576 | 16,842,629 | ConclusionS ystem level interventions implemented in the USA with patients willing to take anti-depressant medication leads to a modest increase in recovery from depression . | Background Primary care is being encouraged to implement multiprofessional , system level , chronic illness management approaches to depression .
We undertook this study to identify and assess the quality of RCTs testing system level depression management interventions in primary care and to determine whether these interventions improve recovery . | Reports of cluster r and omised trials require additional information to allow readers to interpret them accurately The effective reporting of r and omised controlled trials has received useful attention in recent years . Many journals now require that reports conform to the guidelines in the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement , first published in 1996 and revised in 2001 . The statement includes a checklist of items that should be included in the trial report . These items are evidence based whenever possible and are regularly review ed . The statement also recommends including a flow diagram to show the flow of participants from group assignment through to the final analysis . The CONSORT statement focused on reporting parallel group r and omised trials in which individual participants are r and omly assigned to study groups . However , in some situations it is preferable to r and omly assign groups of individuals ( such as families or medical practice s ) rather than individuals . Reasons include the threat of contamination of some interventions ( such as dietary interventions ) if individual r and omisation is used . 5 Also , in certain setting s r and omisation by group may be the only feasible method of conducting a trial . Trials with this design are variously known as field trials , community based trials , place based trials , or ( as in this paper ) cluster r and omised trials . In an earlier discussion paper we considered the implication s of the CONSORT statement for the reporting of cluster r and omised trials . Here we present up date d guidance , based on the 2001 revision of the CONSORT statement BACKGROUND Quality improvement ( QI ) programs for depressed primary care patients can improve health outcomes for 6 to 28 months ; effects for longer than 28 months are unknown . OBJECTIVE To assess how QI for depression affects health outcomes , quality of care , and health outcome disparities at 57-month follow-up . DESIGN A group-level r and omized controlled trial . SETTING Forty-six primary care practice s in 6 managed care organizations . PATIENTS Of 1356 primary care patients who screened positive for depression and enrolled in the trial , 991 ( 73 % , including 451 Latinos and African Americans ) completed 57-month telephone follow-up . INTERVENTIONS Clinics were r and omly assigned to usual care or to 1 of 2 QI programs supporting QI teams , provider training , nurse assessment , and patient education , plus re sources to support medication management ( QI-meds ) or psychotherapy ( QI-therapy ) for 6 to 12 months . MAIN OUTCOME MEASURES Probable depressive disorder in the previous 6 months , mental health-related quality of life in the previous 30 days , primary care or mental health specialty visits , counseling or antidepressant medications in the previous 6 months , and unmet need , defined as depressed but not receiving appropriate care . RESULTS Combined QI-meds and QI-therapy , relative to usual care , reduced the percentage of participants with probable disorder at 5 years by 6.6 percentage points ( P = .04 ) . QI-therapy improved health outcomes and reduced unmet need for appropriate care among Latinos and African Americans combined but provided few long-term benefits among whites , reducing outcome disparities related to usual care ( P = .04 for QI-ethnicity interaction for probable depressive disorder ) . CONCLUSIONS Programs for QI for depressed primary care patients implemented by managed care practice s can improve health outcomes 5 years after implementation and reduce health outcome disparities by markedly improving health outcomes and unmet need for appropriate care among Latinos and African Americans relative to whites ; thus , equity was improved in the long run It is difficult to evaluate the promise of primary care quality -improvement interventions for depression because published studies have evaluated diverse interventions by using different research design s in dissimilar population s. Preplanned meta- analysis provides an alternative to derive more precise and generalizable estimates of intervention effects ; however , this approach requires the resolution of analytic challenges result ing from design differences that threaten internal and external validity . This paper describes the four-project Quality Improvement for Depression ( QID ) collaboration specifically design ed for preplanned meta- analysis of intervention effects on outcomes . This paper summarizes the interventions the four projects tested , characterizes commonalities and heterogeneity in the research design s used to evaluate these interventions , and discusses the implication s of this heterogeneity for preplanned meta- analysis Abstract Objectives : To evaluate the long term effect of ongoing intervention to improve treatment of depression in primary care . Design : R and omised controlled trial . Setting : Twelve primary care practice s across the United States . Participants : 211 adults beginning a new treatment episode for major depression ; 94 % of patients assigned to ongoing intervention participated . Intervention : Practice s assigned to ongoing intervention encouraged participating patients to engage in active treatment , using practice nurses to provide care management over 24 months . Main outcome measures : Patients ' report of remission and functioning . Results : Ongoing intervention significantly improved both symptoms and functioning at 24 months , increasing remission by 33 percentage points ( 95 % confidence interval 7 % to 46 % ) , improving emotional functioning by 24 points ( 11 to 38 ) and physical functioning by 17 points ( 6 to 28 ) . By 24 months , 74 % of patients in enhanced care reported remission , with emotional functioning exceeding 90 % of population norms and physical functioning approaching 75 % of population norms . Conclusions : Ongoing intervention increased remission rates and improved indicators of emotional and physical functioning . Studies are needed to compare the cost effectiveness of ongoing depression management with other chronic disease treatment routinely undertaken by primary care BACKGROUND This article addresses whether dissemination of short-term quality improvement ( QI ) interventions for depression to primary care practice s improves patients ' clinical outcomes and health-related quality of life ( HRQOL ) over 2 years , relative to usual care ( UC ) . METHODS The sample included 1299 patients with current depressive symptoms and 12-month , lifetime , or no depressive disorder from 46 primary care practice s in 6 managed care organizations . Clinics were r and omized to UC or 1 of 2 QI programs that included training local experts and nurse specialists to provide clinician and patient education , assessment , and treatment planning , plus either nurse care managers for medication follow-up ( QI-meds ) or access to trained psychotherapists ( QI-therapy ) . Outcomes were assessed every 6 months for 2 years . RESULTS For most outcomes , differences between intervention and UC patients were not sustained for the full 2 years . However , QI-therapy reduced overall poor outcomes compared with UC by about 8 percentage points throughout 2 years , and by 10 percentage points compared with QI-meds at 24 months . Both interventions improved patients ' clinical and role outcomes , relative to UC , over 12 months ( eg , a 10 - 11 and 6 - 7 percentage point difference in probable depression at 6 and 12 months , respectively ) . CONCLUSIONS While most outcome improvements were not sustained over the full 2 study years , findings suggest that flexible dissemination of short-term , QI programs in managed primary care can improve patient outcomes well after program termination . Models that support integrated psychotherapy and medication-based treatment strategies in primary care have the potential for relatively long-term patient benefits BACKGROUND The diagnosis and treatment of depression constitutes a significant component of a general practitioner 's workload . A pilot study has suggested that the practice nurse may have an important contribution to make in the care of patients with depression . AIM To evaluate an extended role for practice nurses in improving the outcome of depression through two specially- design ed interviews running in parallel . METHOD Two naturalistic , r and om allocation studies took place concurrently over four months . Study 1 evaluated the effectiveness of st and ardized psychiatric assessment by a practice nurse and feedback of information to the general practitioner ( GP ) . Study 2 evaluated the above assessment and feedback combined with nurse-assisted follow-up care . Twenty general practice s participating in the Medical Research Council General Practice Research Framework took part in the study . Subjects included general practice attenders identified as depressed by their GP . The main outcome measures were a change in Beck Depression Inventory ( BDI ) scores and in the proportion of patients fulfilling DSM-III criteria for major depression . RESULTS A total of 577 patients were recruited ; 516 [ 89 % ( 95 % CI = 86 - 92 % ) ] were rated as depressed on the BDI and 474 [ 82 % ( 95 % CI = 79 - 85 % ) ] met criteria for DSM-III major depression . Altogether , 524 ( 91 % ) patients completed follow-up at four months . All groups of patients showed improvement , but no difference in the rate of improvement was shown for the nurse intervention groups . BDI mean scores fell from 18.54 ( 95 % CI = 17.53 - 20.06 ) to 11.53 ( 95 % CI = 10.02 - 13.04 ) in Study 1 , and from 21.01 ( 95 % = CI 20.26 - 21.86 ) to 10.62 ( 95 % CI = 9.73 - 11.51 ) in Study 2 . The proportion of patients fulfilling criteria for DSM-III major depression in Study 1 fell from 80 % ( 95 % CI = 73 - 87 % ) to 30 % ( 95 % CI = 22 - 38 % ) , and in Study 2 from 80 % ( 95 % CI = 76 - 84 % ) to 27 % ( 95 % CI = 23 - 31 % ) . Prescription rates of antidepressant medication were higher than expected , ranging between 63 % and 76 % in the two studies . CONCLUSION There was an increase in the rate of antidepressant prescription , but no additional benefit could be adduced for patients who received a nurse intervention BACKGROUND Despite improvements in the accuracy of diagnosing depression and use of medications with fewer side effects , many patients treated with antidepressant medications by primary care physicians have persistent symptoms . METHODS A group of 228 patients recognized as depressed by their primary care physicians and given antidepressant medication who had either 4 or more persistent major depressive symptoms or a score of 1.5 or more on the Hopkins Symptom Checklist depression items at 6 to 8 weeks were r and omized to a collaborative care intervention ( n = 114 ) or usual care ( n = 114 ) by the primary care physician . Patients in the intervention group received enhanced education and increased frequency of visits by a psychiatrist working with the primary care physician to improve pharmacologic treatment . Follow-up assessment s were completed at 1 , 3 , and 6 months by a telephone survey team blinded to r and omization status . RESULTS Those in the intervention group had significantly greater adherence to adequate dosage of medication for 90 days or more and were more likely to rate the quality of care they received for depression as good to excellent compared with usual care controls . Intervention patients showed a significantly greater decrease compared with usual care controls in severity of depressive symptoms over time and were more likely to have fully recovered at 3 and 6 months . CONCLUSIONS A multifaceted program targeted to patients whose depressive symptoms persisted 6 to 8 weeks after initiation of antidepressant medication by their primary care physician was found to significantly improve adherence to antidepressants , satisfaction with care , and depressive outcomes compared with usual care Objectives : Screening is advocated to improve the recognition of patients with major depression in primary care . Furthermore , disease management programmes are advocated to improve the quality of care and outcome for these patients . But is screening and the subsequent implementation of a disease management programme more effective than usual care ? Methods : Review of the literature on the effects of disease management programmes that include screening for major depression in general practice . Results : Six r and omised controlled trials were identified in which the effectiveness of disease management programmes were studied in patients with major depression in primary care and compared with usual care . The majority of these , and especially the largest , showed positive effects on the recognition , diagnosis , treatment and outcome of patients . Population s in the US seem to benefit most . Conclusion : The results of disease management programmes for depression in primary care that include screening are positive and are more effective than usual care . Therefore , if preceded by screening , attention to the whole process of care for patients with major depression instead of paying attention to isolated elements of the process is justified Most depressed patients are seen and treated exclusively by primary care clinicians . However , primary care patients with depression are often not adequately treated . The aims of this pilot study were to measure the impact of a telephone disease management program on patient outcome and clinician adherence to practice guidelines , measure the relationship of clinician adherence to patient outcome , and explore the measurement of patient adherence to clinician recommendations and its impact on patient outcomes . Thirty-five primary care practice s in the University of Pennsylvania Health System were r and omized to telephone disease management ( TDM ) or " usual care " ( UC ) . All patients received a baseline and a 16-week follow-up clinical evaluation performed over the telephone . Those from TDM practice s also received follow-up contact at least every 3 weeks , with formal evaluations at weeks 6 and 12 . These interval contacts were design ed to facilitate patient and clinician adherence to a treatment algorithm based on the Agency for Health Research and Quality ( AHRQ ) practice guidelines . Depressive symptoms evaluated with the Community Epidemiologic Survey of Depression ( CES-D ) scale as well as guideline adherence were the primary outcome measures . Sixty-one patients were enrolled in this pilot project . The overall effect for CES-D scores over time was significant , ( P < .001 ) , indicating that those participating in the trial ( both TDM and UC groups ) showed significant improvement . The interaction between intervention condition and time was also significant ( P < .05 ) , indicating that TDM patients improved significantly more over time than did UC patients . A greater proportion of TDM patients had CES-D scores < 16 by Week 16 ( 66.7 versus 33.3 % ; chi(2 ) , P < .05 ) . The improvement in depression outcome for the TDM group was related to its impact on improving clinician adherence to depression treatment algorithms . The TDM pilot did not show a statistically significant effect on improving patient adherence to clinician recommendations , however . This preliminary data suggests that TDM for depression improves both clinician guideline adherence and patient outcomes in the acute phase of depression . The effect on patient outcome is at least partially explained by the effect of TDM on clinician adherence to depression treatment algorithms CONTEXT Care of patients with depression in managed primary care setting s often fails to meet guideline st and ards , but the long-term impact of quality improvement ( QI ) programs for depression care in such setting s is unknown . OBJECTIVE To determine if QI programs in managed care practice s for depressed primary care patients improve quality of care , health outcomes , and employment . DESIGN R and omized controlled trial initiated from June 1996 to March 1997 . SETTING Forty-six primary care clinics in 6 US managed care organizations . PARTICIPANTS Of 27332 consecutively screened patients , 1356 with current depressive symptoms and either 12-month , lifetime , or no depressive disorder were enrolled . INTERVENTIONS Matched clinics were r and omized to usual care ( mailing of practice guidelines ) or to 1 of 2 QI programs that involved institutional commitment to QI , training local experts and nurse specialists to provide clinician and patient education , identification of a pool of potentially depressed patients , and either nurses for medication follow-up or access to trained psychotherapists . MAIN OUTCOME MEASURES Process of care ( use of antidepressant medication , mental health specialty counseling visits , medical visits for mental health problems , any medical visits ) , health outcomes ( probable depression and health-related quality of life [ HRQOL ] ) , and employment at baseline and at 6- and 12-month follow-up . RESULTS Patients in QI ( n = 913 ) and control ( n = 443 ) clinics did not differ significantly at baseline in service use , HRQOL , or employment after nonresponse weighting . At 6 months , 50.9 % of QI patients and 39.7 % of controls had counseling or used antidepressant medication at an appropriate dosage ( P<.001 ) , with a similar pattern at 12 months ( 59.2 % vs 50.1 % ; P = .006 ) . There were no differences in probability of having any medical visit at any point ( each P > or = .21 ) . At 6 months , 47.5 % of QI patients and 36.6 % of controls had a medical visit for mental health problems ( P = .001 ) , and QI patients were more likely to see a mental health specialist at 6 months ( 39.8 % vs 27.2 % ; P<.001 ) and at 12 months ( 29.1 % vs 22.7 % ; P = .03 ) . At 6 months , 39.9 % of QI patients and 49.9 % of controls still met criteria for probable depressive disorder ( P = .001 ) , with a similar pattern at 12 months ( 41.6 % vs 51.2 % ; P = .005 ) . Initially employed QI patients were more likely to be working at 12 months relative to controls ( P = .05 ) . CONCLUSIONS When these managed primary care practice s implemented QI programs that improve opportunities for depression treatment without m and ating it , quality of care , mental health outcomes , and retention of employment of depressed patients improved over a year , while medical visits did not increase overall This article uses longitudinal data from a primary care sample to examine long-term prognosis of depression . A sample of 225 patients initiating antidepressant treatment in primary care completed assessment s of clinical outcome ( Hamilton Depression Rating Scale and the mood module of the Structured Clinical Interview for DSM-IIIR ) 1 , 3 , 6 , 9 , 12 , 18 and 24 months after initiating treatment . The proportion of patients continuing to meet criteria for major depression fell rapidly to approximately 10 % and remained at approximately that level throughout follow-up . The proportion meeting criteria for remission ( Hamilton Depression score of 7 or less ) rose gradually to approximately 45 % . Long-term prognosis ( i.e. probability of remission at 6 months and beyond ) was strongly related to remission status at 3 months ( odds ratio 3.65 ; 95 % confidence interval , 2.81 - 4.76 ) and only modestly related to various clinical characteristics assessed at baseline ( e.g. prior history of recurrent depression , medical comorbidity , comorbid anxiety symptoms ) . The findings indicate that potentially modifiable risk factors influence the long-term prognosis of depression . This suggests that more systematic and effective depression treatment programmes might have an important effect on long-term course and reduce the overall burden of chronic and recurrent depression BACKGROUND This research study evaluates the effectiveness of a multifaceted intervention program to improve the management of depression in primary care . METHODS One hundred fifty-three primary care patients with current depression were entered into a r and omized controlled trial . Intervention patients received a structured depression treatment program in the primary care setting that included both behavioral treatment to increase use of adaptive coping strategies and counseling to improve medication adherence . Control patients received " usual " care by their primary care physicians . Outcome measures included adherence to antidepressant medication , satisfaction with care of depression and with antidepressant treatment , and reduction of depressive symptoms over time . RESULTS At 4-month follow-up , significantly more intervention patients with major and minor depression than usual care patients adhered to antidepressant medication and rated the quality of care they received for depression as good to excellent . Intervention patients with major depression demonstrated a significantly greater decrease in depression severity over time compared with usual care patients on all 4 outcome analyses . Intervention patients with minor depression were found to have a significant decrease over time in depression severity on only 1 of 4 study outcome analyses compared with usual care patients . CONCLUSION A multifaceted primary care intervention improved adherence to antidepressant regimens and satisfaction with care in patients with major and minor depression . The intervention consistently result ed in more favorable depression outcomes among patients with major depression , while outcome effects were ambiguous among patients with minor depression To measure the effects of a collaborative care model that emphasized the role of clinical pharmacists in providing drug therapy management and treatment follow-up to patients with depression , we conducted a r and omized controlled trial at a staff model health maintenance organization . We compared the outcomes of subjects treated in this collaborative care model ( 75 patients , intervention group ) with subjects receiving usual care ( 50 patients , control group ) . After 6 months , the intervention group demonstrated a significantly higher drug adherence rate than that of the control group ( 67 % vs 48 % , odds ratio 2.17 , 95 % confidence interval 1.04 - 4.51 , p=0.038 ) . Patient satisfaction was significantly greater among members r and omly assigned to pharmacists ' services than among controls , and provider satisfaction surveys revealed high approval rates as well . Changes in re source utilization were favorable for the intervention group , but differences from the control group did not achieve statistical significance . Clinical improvement was noted in both groups , but the difference was not significant . Clinical pharmacists had a favorable effect on multiple aspects of patient care . Future studies of this model in other health care setting s appear warranted Complex interventions , which have been shown to improve primary care depression outcomes , are difficult to disseminate to routine practice setting s. To address this problem , we developed a brief intervention to train primary care physicians and nurses employed by the practice to improve the detection and management of major depression . Before recruitment began , the research team conducted academic detailing conference calls with primary care physicians and nurses , and provided in-person training with nurses and administrative staff . Administrative staff screened over 11,000 patients before their visits to identify those with probable major depression . Primary care physicians delegated increased responsibility to office nurses , who educated over 90 % of patients about effective depression treatment and systematic ally monitored their progress over time . Early results demonstrate that community primary care practice s can rebundle traditional team roles over the short-term to provide more systematic mental health treatment without adding additional personnel . A rigorous evaluation of this effort will reduce time-consuming , expensive , and often unsuccessful efforts to " translate " research intervention findings into everyday practice PURPOSE The impact of pharmacist interventions on the care and outcomes of patients with depression in a primary care setting was evaluated . METHODS Patients diagnosed with a new episode of depression and started on anti-depressant medications were r and omized to enhanced care ( EC ) or usual care ( UC ) for one year . EC consisted of a pharmacist collaborating with primary care providers to facilitate patient education , the initiation and adjustment of antidepressant dosages , the monitoring of patient adherence to the regimen , the management of adverse reactions , and the prevention of relapse . The patients in the UC group served as controls . Outcomes were measured by the Hopkins Symptom Checklist , Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria for major depression , health-related quality of life , medication adherence , patient satisfaction , and use of depression-related health care services . An intent-to-treat analysis was used . RESULTS Seventy-four patients were r and omized to EC or UC . At baseline , the EC group included more patients diagnosed with major depression than did the UC group ( p = 0.04 ) . All analyses were adjusted for this difference . In both groups , mean scores significantly improved from baseline for symptoms of depression and quality of life at three months and were maintained for one year . There were no statistically significant differences between treatment groups in depression symptoms , quality of life , medication adherence , provider visits , or patient satisfaction . CONCLUSION Frequent telephone contacts and interventions by pharmacists and UC in a primary care setting result ed in similar rates of adherence to antidepressant regimens and improvements in the outcomes of depression at one year OBJECTIVE : To develop a pharmacist intervention to improve depression care and outcomes within a primary care setting . METHODS : Pragmatic , r and omized trial of a clinical pharmacist collaborative care intervention versus usual care in a busy , academic family practice clinic . RESULTS : Seventy-four patients diagnosed with a new episode of major depression and started on antidepressant medications were r and omized to enhanced care ( EC ) or usual care ( UC ) groups . EC consists of a clinical pharmacist collaborating with primary care providers ( PCPs ) to facilitate education , initiation , and titration of acute-phase antidepressant treatment to monitor treatment adherence and to prevent relapse . Control patients receive UC by their PCP . The main end point is reduction of depression symptoms over time as measured by the Hopkins Symptom Checklist ( SCL-20 ) . Other outcomes include the Diagnostic and Statistical Manual of Mental Disorders , ( DSM-IV ) criteria for major depression , health-related quality of life measured by the Medical Outcomes Study Short Form 12 ( SF-12 ) , medication adherence , patient satisfaction , and healthcare utilization . The main end point and the cost of treating major depression will be used to estimate the cost-effectiveness of the collaborative care model . CONCLUSIONS : The study is a unique , ongoing trial that may have important implication s for the treatment of depression in primary care setting s as well as new roles for clinical pharmacists BACKGROUND Cognitive-behavioural therapy ( CBT ) brings about significant clinical improvement in anxiety and depression , but therapists are in short supply . We report the first phase of a r and omized controlled trial of an interactive multimedia program of cognitive-behavioural techniques , Beating the Blues ( BtB ) , in the treatment of patients in general practice with anxiety , depression or mixed anxiety/depression . METHOD One hundred and sixty-seven adults suffering from anxiety and /or depression and not receiving any form of psychological treatment or counselling were r and omly allocated to receive , with or without medication , BtB or treatment as usual ( TAU ) . Measures were taken on five occasions : prior to treatment , 2 months later , and at 1 , 3 and 6 months follow-up using the Beck Depression Inventory , Beck Anxiety Inventory and Work and Social Adjustment Scale . RESULTS Patients who received BtB showed significantly greater improvement in depression and anxiety compared to TAU by the end of treatment ( 2 months ) and to 6 months follow-up . Symptom reduction was paralleled by improvement in work and social adjustment . There were no interactions of BtB with concomitant pharmacotherapy or duration of illness , but evidence , on the Beck Anxiety Inventory only , of interaction with primary care practice . Importantly , there was no interaction between the effects of BtB and baseline severity of depression , from which we conclude that the effects of the computer program are independent of starting level of depression . CONCLUSIONS These results demonstrate that computerized interactive multimedia cognitive-behavioural techniques under minimal clinical supervision can bring about improvements in depression and anxiety , as well as in work and social adjustment , with and without pharmacotherapy and in patients with pre-treatment illness of duration s greater or less than 6 months . Thus , our results indicate that wider dissemination of cognitive-behavioural techniques is possible for patients suffering from anxiety and /or depression BACKGROUND High utilizers of nonpsychiatric health care services have disproportionally high rates of undiagnosed or undertreated depression . OBJECTIVE To determine the impact of offering a systematic primary care-based depression treatment program to depressed " high utilizers " not in active treatment . DESIGN R and omized clinical trial . SETTING One hundred sixty-three primary care practice s in 3 health maintenance organizations located in different geographic regions of the United States . PATIENTS A group of 1465 health maintenance organization members were identified as depressed high utilizers using a 2-stage telephone screening process . Eligibility criteria were met by 410 patients and 407 agreed to enroll : 218 in the depression management program ( DMP ) practice s and 189 in the usual care ( UC ) group . INTERVENTION The DMP included patient education material s , physician education programs , telephone-based treatment coordination , and antidepressant pharmacotherapy initiated and managed by patients ' primary care physicians . MAIN OUTCOME MEASURES Depression severity was measured using the Hamilton Depression Rating Scale ( Ham-D ) and functional status using the Medical Outcomes Study 20-item short form ( SF-20 ) subscales . Outpatient visit and hospitalization rates were measured using the health plan 's encounter data . RESULTS Based on an intent-to-treat analysis , at least 3 antidepressant prescriptions were filled in the first 6 months by 151 ( 69.3 % ) of 218 of DMP patients vs 35 ( 18.5 % ) of 189 in UC ( P < .001 ) . Improvements in Ham-D scores were significantly greater in the intervention group at 6 weeks ( P = .04 ) , 3 months ( P = .02 ) , 6 months ( P < .001 ) , and 12 months ( P < .001 ) . At 12 months , DMP intervention patients were more improved than UC patients on the mental health , social functioning , and general health perceptions scales of the SF-20 ( P < .05 for all ) . CONCLUSION In depressed high utilizers not already in active treatment , a systematic primary care-based treatment program can substantially increase adequate antidepressant treatment , decrease depression severity , and improve general health status compared with usual care Abstract OBJECTIVE : To determine whether redefining primary care team roles would improve outcomes for patients beginning a new treatment episode for major depression . DESIGN : Following stratification , 6 of 12 practice s were r and omly assigned to the intervention condition . Intervention effectiveness was evaluated by patient reports of 6-month change in 100-point depression symptom and functional status scales . SETTING : Twelve community primary care practice s across the country employing no onsite mental health professional . PATIENTS : Using two-stage screening , practice s enrolled 479 depressed adult patients ( 73.4 % of those eligible ) ; 90.2 % completed six-month follow-up . INTERVENTION : Two primary care physicians , one nurse , and one administrative staff member in each intervention practice received brief training to improve the detection and management of major depression . MAIN RESULTS : In patients beginning a new treatment episode , the intervention improved depression symptoms by 8.2 points ( 95 % confidence interval [ CI ] , 0.2 to 16.1 ; P=.04 ) . Within this group , the intervention improved depression symptoms by 16.2 points ( 95 % CI , 4.5 to 27.9 ; P=.007 ) , physical role functioning by 14.1 points ( 95 % CI , 1.1 to 29.2 ; P=.07 ) , and satisfaction with care ( P=.02 ) for patients who reported antidepressant medication was an acceptable treatment at baseline . Patients already in treatment at enrollment did not benefit from the intervention . CONCLUSIONS : In practice s without onsite mental health professionals , brief interventions training primary care teams to assume redefined roles can significantly improve depression outcomes in patients beginning a new treatment episode . Such interventions should target patients who report that antidepressant medication is an acceptable treatment for their condition . More research is needed to determine how primary care teams can best sustain these redefined roles over time BACKGROUND Recent trials have shown improved depression outcomes with chronic care models . We report the methods of a project that assesses the sustainability and transportability of a chronic care model for depression and change strategy . METHODS In a r and omized controlled trial ( RCT ) , a clinical model for depression was implemented through a strategy supporting practice change . The clinical model is evidence based . The change strategy relies on established quality improvement programs and is informed by diffusion of innovations theory . Evaluation will address patient outcomes , as well as process of care and process of change . RESULTS Five medical groups and health plans are participating in the trial . The RCT involves 180 clinicians in 60 practice s. All practice s assigned to the clinical model have implemented it . Participating organizations have the potential to disseminate this clinical model of care to 700 practice s and 1,700 clinicians . CONCLUSIONS It is feasible to implement the clinical model and change strategy in diverse practice s. Follow-up evaluation will determine the impact , sustainability , and potential for dissemination . Material s are available through http://www.depression- primary care.org ; more in-depth descriptions of the clinical model and change strategy are available in the online-only appendixes to this article In 1970 L G Kiloh and I finished recruiting patients for a prospect i ve study of depression in admissions to a new general hospital psychiatric unit . When we published the 15 year follow up we discovered that our patients had not done at all well.1 Only a fifth recovered and remained continuously well , three fifths recovered but had further episodes , and a fifth either committed suicide or were always incapacitated . An English 15 year follow up study published at the same time showed identical results .2 The obvious conclusion was that people admitted to hospital in the 1970s with a depressive illness did not have a good prognosis . In retrospect , I ask why more of those who relapsed did not return to us for treatment . These results are not atypical . A detailed 12 year follow up in US specialist care showed that patients on average had symptoms in 59 % of weeks and met full criteria for a depressive episode in 15 % of weeks.3 Depression seems to be a chronic recurring disorder , seldom well managed if one simply waits for the patient to initiate further consultations . # # # # Summary points The burden of depression is not being reduced The episodic nature of depression and the acute response to treatment means that episodes seem easy to treat They can be if patients comply with drug and cognitive therapy regimens The main problem is the next recurrence , if patients do not to come for treatment at all To reduce the burden of depression , we argue for a chronic disease management model We should manage depression proactively to ensure long term compliance with treatment I identified references to remission and relapse of depression during the writing up of the Australian national mental health survey . References to long term prognosis came from my earlier work . A conference question , C ausal inferences about the effects of treatments must always depend on best judgments . Because the lives and wellbeing of patients will be influenced for better or worse by the validity of these judgments , however , it is important to be explicit about the logic as well as the empirical evidence on which the judgments are based . This issue of the BMJ is about one important aspect of that logic — the attempt to control bias through r and omisation . There is a growing acceptance that it is logical to try to control biases of various kinds when assessing the effects of treatments . Efforts by clinicians to control biases stretch back for at least three centuries,1 but only during the past 100 years have these become widespread . In particular , as we approach the end of the 20th century , there are now hundreds of thous and s of reports of studies in which efforts have been made to control selection biases , the aim here being to distinguish differences attributable to treatments from differences that reflect the characteristics ( known and unknown ) of the people who have received treatment . These studies are known as r and omised trials because eligible patients are allocated at r and om to one of two or more alternative forms of care . This |
13,577 | 23,432,154 | RFA had a lower risk of local recurrence ( HR = 0.38 , 95 % CI : 0.15 - 0.96 , P = 0.040 ) , but no difference is seen for distant intrahepatic recurrence .
RFA had higher rates of complete tumor necrosis , but RFA also caused more major complications and was more costly than PEI .
RFA appears superior to PEI with respect to local tumor control and 3-year survival for small HCCs < 3 cm .
RFA was more feasible in patients with HCCs > 2 cm or Child-Pugh A liver function | BACKGROUND AND AIM Radiofrequency ablation ( RFA ) and percutaneous ethanol injection ( PEI ) have been used for patients with hepatocellular carcinomas ( HCCs ) < 3 cm , but there is controversy which of the two methods is superior .
Therefore , we aim ed to conduct a systematic review to assess survival , complete tumor necrosis , recurrence and metastasis , major complications , costs , hospital stays , and posttreatment survival quality of RFA versus PEI for treating small HCCs < 3 cm . | BACKGROUND AND STUDY AIMS Hepatocellular carcinoma ( HCC ) is a major burden on health-care systems worldwide . Although radiofrequency ablation ( RFA ) is currently considered the best technique for coagulative necrosis , the superiority of concomitant use of RFA and percutaneous ethanol injection ( PEI ) needs to be determined . The study was design ed to compare efficacy , safety and rate of survival of patients with HCC assigned to receive combined PEI-RFA versus RFA alone and versus PEI alone . PATIENTS AND METHODS This 3-year study enrolled 90 cirrhotic patients with HCC ( Child 's class A or B , but not class C ) . They were r and omly assigned for either PEI-RFA ( group I ) , RFA alone ( group II ) or PEI alone ( group III ) . The primary end point was ablation of the tumour . The secondary end point was rate of survival and recurrence . RESULTS After the first session , complete ablation was significantly higher in the combination group ( 87.9 % ) compared with the RFA group ( 54.54 % ) . After the second session , complete ablation was achieved in 97.0 % of the combination group and in 84.8 % of the RFA group . Regarding the PEI group , 75 % had complete ablation , whereas 25 % had partial ablation after multiple sessions . The survival rate , 1.5 years later , was significantly higher in group I ( 86.7 % ) compared with group III ( 63.3 % ) . The overall incidence of serious adverse events was nil . CONCLUSION Combined treatment is superior to RFA alone and to PEI alone , in safety and efficacy in patients with HCC Aims : The aim of this study was to compare the outcomes of radiofrequency thermal ablation ( RFTA ) , percutaneous ethanol injection ( PEI ) , and percutaneous acetic acid injection ( PAI ) in the treatment of hepatocellular carcinoma ( HCC ) . Patients and methods : A total of 187 patients with HCCs of 3 cm or less were r and omly assigned to RFTA ( n = 62 ) , PEI ( n = 62 ) , or PAI ( n = 63 ) . Tumour recurrence and survival rates were assessed . Results : One , two , and three year local recurrence rates were 10 % , 14 % , and 14 % in the RFTA group , 16 % , 34 % , and 34 % in the PEI group , and 14 % , 31 % , and 31 % in the PAI group ( RFTA v PEI , p = 0.012 ; RFTA v PAI , p = 0.017 ) . One , two , and three year survival rates were 93 % , 81 % , and 74 % in the RFTA group , 88 % , 66 % , and 51 % in the PEI group , and 90 % , 67 % , and 53 % in the PAI group ( RFTA v PEI , p = 0.031 ; RFTA v PAI , p = 0.038 ) . One , two , and three year cancer free survival rates were 74 % , 60 % , and 43 % in the RFTA group , 70 % , 41 % , and 21 % in the PEI group , and 71 % , 43 % , and 23 % in the PAI group ( RFTA v PEI , p = 0.038 ; RFTA v PAI , p = 0.041 ) . Tumour size , tumour differentiation , and treatment methods ( RFTA v PEI and PAI ) were significant factors for local recurrence , overall survival , and cancer free survival . Major complications occurred in 4.8 % of patients ( two with haemothorax , one gastric perforation ) in the RFTA group and in none in two other groups ( RFTA v PEI and PAI , p = 0.035 ) . Conclusions : RFTA was superior to PEI and PAI with respect to local recurrence , overall survival , and cancer free survival rates , but RFTA also caused more major complications To assess whether ultrasound‐guided percutaneous acetic acid injection is superior to percutaneous ethanol injection in the treatment of small hepatocellular carcinoma ( HCC ) , 60 patients with one to four HCCs smaller than 3 cm were entered onto a r and omized controlled trial . Thirty‐one and 29 patients , respectively , were treated by percutaneous acetic acid injection using 50 % acetic acid or by percutaneous ethanol injection using absolute ethanol . There were no significant differences in age , sex ratio , Child‐Pugh class , size of tumors , or number of tumors between the two groups . When there was no evidence of viable HCC from biopsy , plain and helical dynamic computed tomography , or angiography , the treatment was considered successful and was discontinued . All original tumors were treated successfully by either therapy . However , 8 % of 38 tumors treated with percutaneous acetic acid injection and 37 % of 35 tumors treated with percutaneous ethanol injection developed a local recurrence ( P < .001 ) during the follow‐up periods of 29 ± 8 months and 23 ± 10 months , respectively . The 1‐ and 2‐year survival rates were 100 % and 92 % in percutaneous acetic acid injection and 83 % and 63 % in percutaneous ethanol injection ( P = .0017 ) . A multivariate analysis of prognostic factors revealed that treatment was an independent predictor of survival . The risk ratio of percutaneous acetic acid injection versus percutaneous ethanol injection was 0.120 ( range , 0.027‐0.528;P = .0050 ) . In conclusion , percutaneous acetic acid injection is superior to percutaneous ethanol injection in the treatment of small HCC BACKGROUND & AIMS The aim of this study was to compare the clinical outcome of percutaneous radiofrequency ( RF ) ablation , conventional percutaneous ethanol injection ( PEI ) , and higher-dose PEI in treating hepatocellular carcinoma ( HCC ) 4 cm or less . METHODS A total of 157 patients with 186 HCCs 4 cm or less were r and omly assigned to 3 groups ( 52 patients in the conventional PEI group , 53 in the higher-dose PEI group , and 52 in the RF group ) . Clinical outcomes in terms of complete tumor necrosis , overall survival , local tumor progression , additional new tumors , and cancer-free survival were compared across 3 groups . RESULTS The rate of complete tumor necrosis was 88 % in the conventional PEI group , 92 % in the higher-dose PEI group , and 96 % in the RF group . Significantly fewer sessions were required to achieve complete tumor necrosis in the RF group than in the other 2 groups ( P < .01 ) . The local tumor progression rate was lowest in the RF group ( vs the conventional PEI group , P = .012 ; vs the higher-dose PEI group , P = .037 ) . The overall survival rate was highest in the RF group ( vs the conventional PEI group , P = .014 ; vs the higher-dose PEI group , P = .023 ) . The cancer-free survival rate was highest in the RF group ( vs the conventional PEI group , P = .019 ; vs the higher-dose PEI group , P = .024 ) . Multivariate analysis determined that tumor size , tumor differentiation , and the method of treatment ( RF vs both methods of PEI ) were significant factors in relation to local tumor progression , overall survival , and cancer-free survival . CONCLUSIONS The results show that RF ablation yielded better clinical outcomes than conventional and higher-dose PEI in treating HCC 4 cm or less AIM To compare 5-year survival of patients with a single hepatocellular carcinoma≤3 cm r and omly assigned to receive percutaneous ethanol injection or radiofrequency ablation . PATIENTS AND METHODS A total of 285 patients ( 192 males , mean age 70 years ) , with a single hepatocellular carcinoma ( mean diameter 2.2 cm ) were r and omly assigned to receive percutaneous ethanol injection ( n=143 ) or radiofrequency ablation ( n=142 ) . The primary endpoint of the study was 5-year survival . RESULTS Overall 143 patients underwent percutaneous ethanol injection and 128 radiofrequency ablation . In consideration of segmental location , in fact , 14 patients with 14 hepatocellular carcinomas could not be treated with established radiofrequency and were treated with percutaneous ethanol injection ; these patients were not included in the survival evaluation . In the percutaneous ethanol injection and in the radiofrequency ablation groups , 3- and 5-year survival rates of 74 % and 68 % , and 78 % and 68 % , and 79 % and 70 % [ corrected ] respectively , were observed ( p = n.s ) . In the percutaneous ethanol injection group , 3- and 5-year local recurrence rates were 9.4 % and 12.8 % respectively ; in the radiofrequency group , the 3 and 5 years local recurrence rates were 7.8 % and 11.7 % , respectively ( p = n.s . ) . The overall costs of percutaneous ethanol injection and radiofrequency ablation were 1359 Euros and 171.000 Euros , respectively ( p<0.0001 ) CONCLUSION Percutaneous ethanol injection and radiofrequency ablation conferred similar 5-year survival . Feasibility is not the same for both procedures . Percutaneous ethanol injection is much cheaper than radiofrequency ablation and should be considered whether in poor and rich countries BACKGROUND Ninety percent of patients with hepatocellular carcinoma ( HCC ) have cirrhosis . Bleeding esophageal varices ( BEV ) is a frequent complication of cirrhosis . Detection of HCC in cirrhotic patients with BEV has not been studied . METHODS Two hundred eleven unselected patients with cirrhosis and BEV were r and omized to endoscopic sclerotherapy ( n = 106 ) or emergency portacaval shunt ( n = 105 ) . Diagnostic workup and treatment were initiated within 8 hours . Ninety-six percent had > 10 years of follow-up . HCC screening involved serum α-fetoprotein ( AFP ) every 3 months , ultrasonography every 6 months , and selective computed tomography ( CT ) . RESULTS HCC occurred in 15 patients , all incurable , a mean of 2.94 years after entry . They died a mean 1.33 years after discovery . Serial AFP and ultrasound examinations were unrevealing over a mean of 2.3 years . The mean model of end-stage liver disease score was 12.7 at entry and 17.4 at HCC diagnosis . CONCLUSIONS Long-term screening by AFP and ultrasound plus selective CT failed to detect HCC at a curable stage . The detection of HCC in cirrhotic patients with BEV remains a serious , unsolved problem . The use of CT for routine screening warrants consideration despite increased costs Objective . To compare percutaneous ethanol injection ( PEI ) , the st and ard approach which has been used for many years to treat early non-surgical hepatocellular carcinoma ( HCC ) in cirrhotic patients , and radiofrequency ablation ( RFA ) , which has become an interesting alternative . Material and methods . A r and omized trial was carried out on 139 cirrhotic patients in Child-Pugh classes A/B with 1–3 nodes of HCC ( diameter 15–30 mm ) , for a total of 177 lesions . Patients were r and omized to receive RFA ( n=70 ) or PEI ( n=69 ) . The primary end-point was complete response ( CR ) 1 year after the percutaneous ablation of all HCC nodes identified at baseline . Secondary end-points were : early ( 30–50 days ) CR , complications , survival and costs . Results . In an intention-to-treat analysis , 1-year CR was achieved in 46/70 ( 65.7 % ) and in 25/69 ( 36.2 % ) patients treated by RFA and PEI , respectively ( p=0.0005 ) . For lesions > 20 mm in diameter , there was a larger CR rate in the RFA group ( 68.1 % versus 26.3 % ) . An early CR was obtained in 67/70 ( 95.7 % ) patients treated by RFA compared with 42/64 ( 65.6 % ) patients treated by PEI ( p=0.0001 ) . Complications occurred in 10 and 12 patients treated by RFA and PEI , respectively . The overall survival rate was not significantly different in the RFA versus PEI arm ( adjusted hazard ratio=0.88 , 95 % CI : 0.50–1.53 ) . There was an incremental health-care cost of 8286 € for each additional patient successfully treated by RFA . Conclusions . The 1-year CR rate after percutaneous treatment of early HCC was significantly better with RFA than with PEI but did not provide a clear survival advantage in cirrhotic patients PURPOSE To compare the effectiveness of radio-frequency ( RF ) thermal ablation with that of percutaneous ethanol injection ( PEI ) for the treatment of small hepatocellular carcinoma ( HCC ) in patients with cirrhosis . MATERIAL S AND METHODS A series of 102 patients with hepatic cirrhosis and either single HCC 5 cm in diameter or smaller or as many as three HCCs each 3 cm or smaller ( overall number of lesions , 142 ) r and omly received either RF ablation ( n = 52 ) or PEI ( n = 50 ) as the sole first-line anticancer treatment . Mean follow-up was 22.9 months + /- 9.4 ( SD ) in the RF group and 22.4 months + /- 8.6 in the PEI group . Prognostic value of treatment techniques was assessed with univariate and multivariate Cox proportional hazards regression models . RESULTS One- and 2-year survival rates were 100 % and 98 % in the RF group and 96 % and 88 % in the PEI group , respectively ( univariate relative risk [ RR ] = 0.20 ; 95 % CI : 0.02 , 1.69 ; P = .138 ) . One- and 2-year local recurrence-free survival rates were 98 % and 96 % in the RF group and 83 % and 62 % in the PEI group , respectively ( univariate RR = 0.17 ; 95 % CI : 0.06 , 0.51 ; P = .002 ) . One- and 2-year event-free survival rates were 86 % and 64 % for the RF group and 77 % and 43 % for the PEI group , respectively ( univariate RR = 0.48 ; 95 % CI : 0.27 , 0.85 ; P = .012 ) . RF treatment was confirmed as an independent prognostic factor for local recurrence-free survival rates with multivariate analysis ( adjusted RR = 0.20 ; 95 % CI : 0.05 , 0.73 ; P = .015 ) . CONCLUSION RF ablation is superior to PEI with respect to local recurrence-free survival rates Objective : To compare disease recurrence and survival among patients with small hepatocellular carcinoma after surgical resection or percutaneous ethanol injection therapy , 2 treatments that have not been evaluated with a prospect i ve study . Methods : A total of 76 patients were r and omly assigned to 2 groups based on treatment ; all had one or 2 tumors with diameter ≤3 cm , with hepatitis without cirrhosis or Child class A or B cirrhosis without evident ascites or bleeding tendency . Results : Follow-up ranged from 12 to 59 months . Among percutaneous injection patients , 18 had recurrence 1 to 37 months after treatment ( true recurrence , 11 ; original safety margin inadequate , 3 ; limitation of imaging technology to detect tiny tumors , 4 ) . Three injection therapy patients died of cancer 25 , 37 , and 57 months after treatment . For the surgical resection group , 15 had recurrence 2 to 54 months after treatment ( true recurrence , 12 ; limitation of imaging , 2 ; neck metastasis , 1 ) . Five resection patients died of cancer at 11 , 20 , 23 , 26 , and 52 months , respectively . By Cox regression model and Kaplan-Meier survival analysis , there is no statistical significance for recurrence and survival between treatment groups . However , tumor size larger than 2 cm and alpha-fetoprotein over 200 ng/mL correlated with higher recurrence rate , and Child class B liver cirrhosis correlated with shorter survival . Conclusions : Percutaneous ethanol injection therapy appears to be as safe and effective as resection , and both treatments can be considered first-line options for small hepatocellular carcinoma BACKGROUND & AIMS Percutaneous radiofrequency ablation is a recently introduced treatment for hepatocellular carcinoma , whereas ethanol injection is now a st and ard therapy . We compared their long-term outcomes . METHODS Two hundred thirty-two patients with hepatocellular carcinoma who had 3 or fewer lesions , each 3 cm or less in diameter , and liver function of Child-Pugh class A or B were entered onto a r and omized controlled trial . The primary end point was survival , and the secondary end points were overall recurrence and local tumor progression . RESULTS One hundred eighteen patients were assigned to radiofrequency ablation and 114 to ethanol injection . The number of treatment sessions was smaller ( 2.1 times vs 6.4 times , respectively , P < .0001 ) and the length of hospitalization was shorter ( 10.8 days vs 26.1 days , respectively , P < .0001 ) in radiofrequency ablation than in ethanol injection . Four-year survival rate was 74 % ( 95 % CI : 65%-84 % ) in radiofrequency ablation and 57 % ( 95 % CI : 45%-71 % ) in ethanol injection . Radiofrequency ablation had a 46 % smaller risk of death ( adjusted relative risk , 0.54 [ 95 % CI : 0.33 - 0.89 ] , P = .02 ) , a 43 % smaller risk of overall recurrence ( adjusted relative risk 0.57 [ 95 % CI : 0.41 - 0.80 ] , P = .0009 ) , and an 88 % smaller risk of local tumor progression ( relative risk , 0.12 [ 95 % CI : 0.03 - 0.55 ] , P = .006 ) than ethanol injection . The incidence of adverse events was not different between the 2 therapies . CONCLUSIONS Judging from higher survival but similar adverse events , radiofrequency ablation is superior to ethanol injection for small hepatocellular carcinoma |
13,578 | 23,706,309 | The Pittsburgh sleep quality index and Epworth sleepiness scale were partially vali date d in post-acute TBI .
Although no instrument has been specifically developed for TBI patients , there are scientific benefits to using the existing measures . | null | null |
13,579 | 19,491,350 | Overall , student attitudes were positive towards CAL .
No conclusions can be drawn about the time efficiency of CAL . | The purpose of this systematic review and meta- analysis was to compare the efficacy of computer-assisted learning ( CAL ) with traditional methods of learning in orthodontic education . | Orthodontic records- study models , panoramic and cephalometric radiographs , and the patient 's facial and intraoral photographs-are used to collect data to establish a diagnosis and to develop problem-solution lists . These records , however , can be damaged or lost when dispensed to students and need to be stored and maintained every year . An orthodontic diagnosis web site , therefore , has been set up using digital records to provide students with an accessible source of complete , good- quality study material s. The web site is also used for clinical examination in orthodontic courses . The effectiveness of the web-based digital records in providing relevant information to students in comparison to the traditional records was evaluated by a r and omized controlled trial involving ninety-nine second-year dental students . One group ( fifty students ) studied two cases from the web site ; the other group ( forty-nine students ) studied the same two cases from traditional orthodontic records . Effectiveness was assessed by comparing test scores and the time spent on the tests by t-statistics . There were no significant differences between means for the two study groups in test performance or time . Attitudes of students toward the web site , assessed from post-test question naires , were positive . It was concluded that web-based digital orthodontic records were as effective in teaching clinical orthodontic diagnosis as were conventional records Aim The aim of this study was to compare the effectiveness of a computer assisted learning ( CAL ) programme with that of traditional small group tutorials in teaching theoretical and practical aspects of periodontal pocket charting . Method Sixty-one third year undergraduate dental students were r and omized to either receive a tutorial or to work through the CAL programme . Students using the CAL programme completed question naires relating to previous computer experience and the ease of use of the programme . All students were assessed immediately after the intervention by means of a confidence log , a practical exercise and a further confidence log . They were assessed again three weeks later by means of a confidence log and a multiple-choice written test . Results There were very few significant differences between groups for any of the assessment s used . However , subjective comments indicated that students occasionally felt disadvantaged if they had not received a tutorial . Conclusion CAL and traditional teaching methods are equally effective in teaching periodontal pocket charting to undergraduate dental students AIM The aim of this study was to evaluate the place of computer-aided learning in a basic science course in the undergraduate medical curriculum at the University of Adelaide . METHODS A software program was written which would allow students to study the anatomy and physiology of the liver and biliary tree in three different styles . Identical content was produced , matched for each style ( problem-based , didactic and free text response ) and students r and omly allocated to one of four groups ( three computer and one control ) . Students were tested before and after access to the program . RESULTS Ninety second-year students completed the study . Those students who had access to the material in the problem-based and free text response styles did no better in the post- study test than the controls , whilst the group who had studied the didactically presented computer material performed significantly better than the other three groups . All three computer groups accessed the material on a similar number of occasions , but the group who had access to the free text entry program spent significantly less time on computer study . CONCLUSIONS If computer material s are to be provided as a learning re source for the basic medical sciences , provision must be made for the style of teaching of the course and the style of learning of the students attending that course Hypertext is a non-linear method of text presentation . It necessitates the use of a computer to store data as a series of nodes that can be called up in any desired sequence and , as such , is a new form of discovery-based learning . This paper describes a Hypertext tutorial in cephalometrics and its subsequent testing on first-year clinical dental students . Students were divided into two groups : the first received a conventional lecture ; the second used the Hypertext tutorial . Testing was by means of conventional multiple choice questions . The results showed that there was no statistically significant difference between the two groups , although the computer tutor was shown more consistently to improve the knowledge of the students than did the conventional lecture . Most students who used the computer program found it enjoyable , but time consuming ; less than half found it easy to follow |
13,580 | 19,125,261 | The evidence suggests that patellar resurfacing would reduce the risk of anterior knee pain , as well as the risk of patella-related reoperation .
Furthermore , patients not undergoing patella resurfacing would experience more knee pain during stair climbing and be less satisfied with surgery .
No significant difference in range of motion can be expected with or without patellar resurfacing . | null | null |
13,581 | 19,805,772 | This sequential approach provides a direct measure of the number or proportion of intermediate-risk persons who could be reclassified by the new test .
This type of analysis provides the best information about the clinical effect of using the new test to further stratify intermediate-risk patients . | Clinicians use the Framingham risk score to stratify persons according to their 10-year risk for coronary death or myocardial infa rct ion , also known as major or hard coronary heart disease ( CHD ) events ( 1 , 2 ) .
The Framingham risk score predicts major CHD events well in different demographic and ethnic groups ( 3 ) .
Guidelines recommend using the Framingham risk score , or a modified version of it , to identify high-risk persons ( persons with a 10-year risk > 20 % ) , who benefit from aggressive risk-reduction measures ( 4 , 5 ) .
In the United States , 23 million adults with no history of cardiovascular disease are classified as intermediate-risk by the Framingham score , meaning they have a 10-year risk for major CHD events of 10 % to 20 % ( 6 ) .
New or emerging risk factors , particularly inflammatory markers and markers of atherosclerotic burden , might identify those in this group who are actually at high risk and might benefit from more aggressive risk reduction .
More than 100 emerging risk factors have been proposed for their potential to improve global risk assessment ( 7 ) .
However , consensus conferences held in 1998 ( 8) and 2002 ( 4 , 9 ) recommended against using these factors in the absence of stronger data to support their ability to independently predict CHD events .
Most studies use a hazard ratio ( or other risk ratio ) to measure how well a new risk factor predicts major CHD events , controlling for the Framingham risk factors .
From a clinical viewpoint , calculating a risk ratio is a necessary but far from sufficient step because it does not enable judgment of the effect of using the new test in persons classified as intermediate-risk by the Framingham risk score .
However , a marker that has a small effect on discrimination may have a large effect on the reclassification of persons from 1 risk group to another ( 1318 ) .
To estimate the effect of a new risk factor on reclassification , investigators must compare the proportion of persons classified as high-risk by each model , then assess whether the agreement between the predicted and actual event rates in subgroups of persons who have different levels of risk ( that is , calibration ) has improved .
A better approach is to calculate the Framingham risk score , classify all participants , and then see how well the new risk factor reclassifies those who were assigned to the intermediate-risk group .
Appropriate Control for Confounding With the Framingham Risk Factors Most novel risk factors are correlated with Framingham risk factors , so investigators who do not adjust or adjust inappropriately for 1 or more Framingham factors may overestimate the novel factor 's predictive ability ( 25 , 26 ) . | Background and Purpose — Ultrasound of carotid arteries provides measures of intima media thickness ( IMT ) and plaque , both widely used as surrogate measures of cardiovascular disease . Although IMT and plaques are highly intercorrelated , the relationship between carotid plaque and IMT and cardiovascular disease has been conflicting . In this prospect i ve , population -based study , we measured carotid IMT , total plaque area , and plaque echogenicity as predictors for first-ever myocardial infa rct ion ( MI ) . Methods — IMT , total plaque area , and plaque echogenicity were measured in 6226 men and women aged 25 to 84 years with no previous MI . The subjects were followed for 6 years and incident MI was registered . Results — During follow-up , MI occurred in 6.6 % of men and 3.0 % of women . The adjusted relative risk ( RR ; 95 % CI ) between the highest plaque area tertile versus no plaque was 1.56 ( 1.04 to 2.36 ) in men and 3.95 ( 2.16 to 7.19 ) in women . In women , there was a significant trend toward a higher MI risk with more echolucent plaque . The adjusted RR ( 95 % CI ) in the highest versus lowest IMT quartile was 1.73 ( 0.98 to 3.06 ) in men and 2.86 ( 1.07 to 7.65 ) in women . When we excluded bulb IMT from analyses , IMT did not predict MI in either sex . Conclusions — In a general population , carotid plaque area was a stronger predictor of first-ever MI than was IMT . Carotid atherosclerosis was a stronger risk factor for MI in women than in men . In women , the risk of MI increased with plaque echolucency Abstract — Plasma levels of C-reactive protein ( CRP , a marker of the reactant plasma protein component of the inflammatory response ) and of fibrin D-dimer ( a marker of cross-linked fibrin turnover ) have each been associated in recent studies with the risk of future ischemic heart disease ( IHD ) . Previous experimental studies have shown that fibrin degradation products , including D-dimer , have effects on inflammatory processes and acute-phase protein responses . In the Speedwell Prospect i ve Study , we therefore measured CRP and D-dimer levels in stored plasma sample s from 1690 men aged 49 to 67 years who were followed-up for incident IHD for an average of 75±4 months ( mean±SD ) and studied their associations with each other , with baseline and incident IHD , and with IHD risk factors . CRP and D-dimer levels were each associated with age , plasma fibrinogen , smoking habit , and baseline evidence of IHD . CRP was associated with D-dimer ( r = 0.21 , P < 0.00001 ) . On univariate analyses , both CRP and D-dimer were associated with incident IHD . The incidence of IHD increased with CRP independently of the level of D-dimer ( P = 0.0002 ) and also increased with D-dimer independently of the level of CRP ( P = 0.048 ) . In multivariate analyses , inclusion of D-dimer and conventional risk factors reduced the strength of the association between CRP and incident IHD ; likewise , inclusion of CRP and conventional risk factors reduced the strength of the association between D-dimer and incident IHD . We conclude that although these respective markers of inflammation and fibrin turnover show modest association with each other in middle-aged men , they may have additive associations with risk of incident IHD . Further larger studies are required to test this hypothesis BACKGROUND A high serum total homocysteine ( tHcy ) concentration is a risk factor for death , but the strength of the relation in patients with type 2 ( non-insulin-dependent ) diabetes mellitus compared with nondiabetic subjects is not known . A cross-sectional study suggested that the association between tHcy and cardiovascular disease is stronger in diabetic than in nondiabetic subjects . We therefore prospect ively investigated the combined effect of hyperhomocysteinemia and type 2 diabetes on mortality . METHODS AND RESULTS Between October 1 , 1989 , and December 31 , 1991 , serum was saved from 2484 men and women , 50 to 75 years of age , who were r and omly selected from the town of Hoorn , The Netherl and s. Fasting serum tHcy concentration was measured in 171 subjects who died ( cases ; 76 of cardiovascular disease ) and in a stratified r and om sample of 640 survivors ( control subjects ) . Mortality risks were calculated over 5 years of follow-up by means of logistic regression . The prevalence of hyperhomocysteinemia ( tHcy > 14 micromol/L ) was 25 . 8 % . After adjustment for major cardiovascular risk factors , serum albumin , and HbA(1c ) , the odds ratio ( 95 % CI ) for 5-year mortality was 1.56 ( 1.07 to 2.30 ) for hyperhomocysteinemia and 1.26 ( 1.02 to 1 . 55 ) per 5-micromol/L increment of tHcy . The odds ratio for 5-year mortality for hyperhomocysteinemia was 1.34 ( 0.87 to 2.06 ) in nondiabetic subjects and 2.51 ( 1.07 to 5.91 ) in diabetic subjects ( P=0.08 for interaction ) . CONCLUSIONS Hyperhomocysteinemia is related to 5-year mortality independent of other major risk factors and appears to be a stronger ( 1.9-fold ) risk factor for mortality in type 2 diabetic patients than in nondiabetic subjects In this nested case-control study , lipoprotein ( a ) [ Lp(a ) ] concentrations and apo(a ) isoform size were measured in serum sample s obtained from men participating in the prospect i ve Multiple Risk Factor Intervention Trial ( MRFIT ) . Serum from men aged 35 to 57 years and stored for up to 20 years were analyzed for Lp(a ) levels ( n=736 ) and isoform size ( n=487 ) , respectively . Cases involved nonfatal myocardial infa rct ions ( MI ; n=98 ) , documented during the active phase of the study that ended on February 28 , 1982 and coronary heart disease ( CHD ) deaths ( n=148 ) monitored through 1990 . Median Lp(a ) levels did not differ between cases and controls and mean apo(a ) size did not vary between cases and controls in the entire study population . When adjusted for age and Lp(a ) concentration , logistic regression analysis indicated that small apo(a ) isoforms were associated with CHD deaths among smokers ( OR 3.31 ; 95 % CI 1.07 - 10.28 ) BACKGROUND Epidemiologic studies have shown that C-reactive protein ( CRP ) is a risk factor for coronary heart disease . Whether routine measurement of CRP has a role in the prediction of future coronary disease in everyday clinical practice has not yet been investigated . METHODS Within the Rotterdam Study , a population -based cohort study of 7983 men and women 55 years and older , we conducted a nested case-control study to investigate the value of CRP in coronary disease prediction . Data are based on 157 participants who experienced a myocardial infa rct ion during follow-up and 500 r and omly selected controls . High-sensitivity CRP and traditional cardiovascular risk factors were measured at baseline . RESULTS The age- and sex-adjusted relative risk of myocardial infa rct ion for subjects in the highest quartile of the population distribution of CRP compared with the lowest quartile was 2.0 ( 95 % confidence interval , 1.1 - 3.4 ) . After additional adjustment for traditional cardiovascular risk factors , the increase in risk largely disappeared ( odds ratio , 1.2 ; 95 % confidence interval , 0.6 - 2.2 ) . Adding CRP to a coronary disease risk function based on risk factors that are routinely assessed in clinical practice or to the Framingham risk function did not improve the area under the receiver operating characteristic curve of these risk functions . Sensitivity and specificity of both risk functions , computed after dichotomizing the estimated disease probabilities using prespecified cutoff points , hardly improved when CRP was added . CONCLUSION Measurement of CRP in elderly people has no additional value in coronary disease risk prediction when traditional cardiovascular risk factors are known BACKGROUND We examined the relationship between granulocyte , lymphocyte and monocyte counts and risk of coronary heart disease ( CHD ) and cardiovascular disease ( CVD ) in men and women . There is paucity of data on the differential leucocyte count and its relationship with the risk of CHD and CVD . METHODS This prospect i ve study comprised 7073 men and 9035 women who were 45 - 79 years of age and were residents of Norfolk . United Kingdom . RESULTS During an average of 8 years of follow-up we identified 857 incident CHD events and 2581 CVD incident events . Increased total leucocyte count was associated with increased risk for both CHD and CVD . The highest quartile of granulocyte count was associated with increased risk when compared to lowest quartile for CHD ( men HR 1.70 95 % CI : 1.30 - 2.21 ; women HR 1.24 95 % CI : 0.91 - 1.69 ) and for CVD ( men HR 1.46 95 % CI : 1.24 - 1.71 ; women HR 1.20 95 % CI : 1.02 - 1.42 ) . The association remained unchanged when the analyses were restricted to nonsmokers and when risk was assessed for every 1000 cells L(-1 ) increase in cell count . In multivariable models , despite adjusting for C-reactive protein ( CRP ) , the granulocyte count remained an independent predictor of CHD and CVD risk , especially amongst men . Lymphocyte or monocyte counts were not significantly associated with increased risk . In all analyses , additionally adjusting for CRP did not affect the results material ly . CONCLUSIONS In conclusion , we found that the higher risk for CHD and CVD associated with increased total leucocyte count seems to be accounted for by the increased granulocyte count The relation of serum total homocysteine and lipoprotein(a ) ( Lp(a ) ) with the incidence of atherosclerotic disease was investigated among 7424 men and women aged 40 - 64 years free of atherosclerotic disease at baseline in 1977 . During the 9-year follow-up , 134 male and 131 female cases with either myocardial infa rct ion or stroke were identified . For each case a control subject was selected belonging to the same sex and 5-year age group . Serum sample s collected in 1977 were stored at -20 degrees C and analyzed in 1991 . The mean serum homocysteine concentration of male cases and controls was 9.99 mumol/l and 9.82 mumol/l at baseline and that of female cases and controls 9.58 mumol/l and 9.24 mumol/l , respectively . The median serum Lp(a ) concentration of male cases and controls was 73 mg/l and 108 mg/l and that of female cases and controls 113 mg/l and 91 mg/l , respectively . The differences between cases and controls were not statistically significant . There was also no significant association between either homocysteine or Lp(a ) and atherosclerotic disease , myocardial infa rct ion or stroke in logistic regression analyses . The odds ratios varied from 1.00 to 1.26 for homocysteine and from 0.81 to 1.06 for Lp(a ) . The results of this prospect i ve population -based study do not support the hypotheses that serum homocysteine or Lp(a ) are risk factors for atherosclerotic disease . The lack of association between serum homocysteine and atherosclerotic disease may be due to the exceptionally low gene frequency predisposing to homocysteinemia in Finl and In 1998 , the American Heart Association convened Prevention Conference V to examine strategies for the identification of high-risk patients who need primary prevention . Among the strategies discussed was the measurement of markers of inflammation.1 The Conference concluded that “ many of these markers ( including inflammatory markers ) are not yet considered applicable for routine risk assessment because of : ( 1 ) lack of measurement st and ardization , ( 2 ) lack of consistency in epidemiological findings from prospect i ve studies with endpoints , and ( 3 ) lack of evidence that the novel marker adds to risk prediction over and above that already achievable through the use of established risk factors . ” The National Cholesterol Education Program Adult Treatment Panel III Guidelines identified these markers as emerging risk factors,1a which could be used as an optional risk factor measurement to adjust estimates of absolute risk obtained using st and ard risk factors . Since these publications , a large number of peer- review ed scientific reports have been published relating inflammatory markers to cardiovascular disease ( CVD ) . Several commercial assays for inflammatory markers have become available . As a consequence of the exp and ing research base and availability of assays , the number of inflammatory marker tests ordered by clinicians for CVD risk prediction has grown rapidly . Despite this , there has been no consensus from professional societies or governmental agencies as to how these assays of markers of inflammation should be used in clinical practice . On March 14 and 15 , 2002 , a workshop titled “ CDC/AHA Workshop on Inflammatory Markers and Cardiovascular Disease : Applications to Clinical and Public Health Practice ” was convened in Atlanta , Ga , to address these issues . The goals of this workshop were to determine which of the currently available tests should be used ; what results should be used to define high risk ; which patients should be tested ; and the indications for which the tests would be most useful . These Objective —This study was undertaken to examine the association of plasma inflammatory markers such as C-reactive protein ( CRP ) , interleukin-6 , and fibrinogen with the incidence of coronary heart disease within the prospect i ve cohort study on myocardial infa rct ion ( PRIME study ) . Methods and Results —Multiple risk factors were recorded at baseline in 9758 men aged 50 to 59 years who were free of coronary heart disease ( CHD ) on entry . Nested case-control comparisons were carried out on 317 participants who suffered myocardial infa rct ion (MI)-coronary death ( n=163 ) or angina ( n=158 ) as an initial CHD event during a follow-up for 5 years . After adjustment for traditional risk factors , incident MI-coronary death , but not angina , was significantly associated with CRP , interleukin-6 , and fibrinogen , but only interleukin-6 remained significantly associated with MI-coronary death when the 3 inflammatory markers were included in the model . The different interleukin-6 levels in Northern Irel and and France partly explained the difference in risk between these countries . Interleukin-6 appeared as a risk marker of MI-coronary death , and it improved the definition of CHD risk beyond LDL cholesterol . Conclusions —This association may reflect the underlying inflammatory reaction located in the atherosclerotic plaque or a genetic susceptibility on the part of CHD subjects to answer a proinflammatory stimulus and subsequent increase in hepatic CRP gene expression C-reactive protein ( CRP ) was proposed as a stronger predictor of cardiovascular events than low-density lipoprotein cholesterol ( LDL-C ) ; however , these associations may differ between myocardial infa rct ion ( MI ) and stroke . We compared statistically the associations of CRP and LDL-C levels with risk of MI versus stroke and examined to what extent consideration of CRP or LDL-C increases the population attributable fractions ( PAFs ) of MI and stroke beyond traditional risk factors among 27,548 subjects from the European Prospect i ve Investigation into Cancer and Nutrition-Potsdam Study in a case-cohort design . Among subjects without prior MI or stroke , 156 developed MI and 132 stroke during 6.0 years of follow-up . In adjusted competing risk analyses CRP was positively related to MI and stroke ( P difference between endpoints = 0.55 ) , whereas LDL-C was related to MI but not stroke ( P difference between endpoints = 0.003 ) . The PAF for smoking , diabetes , and hypertension combined was 0.76 for MI , and 0.58 for stroke . With additional consideration of CRP the PAFs were 0.80 and 0.68 , while with addition of LDL-C the PAFs were 0.88 and 0.55 . We conclude that CRP is equally strongly related to risk of MI and stroke , whereas LDL-C is related to risk of MI but not stroke . Consideration of LDL-C beyond smoking , diabetes and hypertension may increase the PAF of MI slightly more than CRP . In contrast , consideration of CRP but not of LDL-C may increase the PAF of stroke beyond these factors Microalbuminuria ( MA ) is associated with increased cardiovascular and all-cause mortality . It has been proposed that MA reflects generalized atherosclerosis and may thus predict mortality . To investigate this hypothesis , we studied the associations between , on the one h and , MA and peripheral arterial disease ( PAD ) , a generally accepted marker of generalized atherosclerosis , and , on the other h and , cardiovascular and all-cause mortality in an age- , sex- , and glucose tolerance-stratified sample ( n=631 ) of a population -based cohort aged 50 to 75 years followed prospect ively for 5 years . At baseline , the albumin-to-creatinine ratio ( ACR ) was measured in an overnight spot urine sample ; MA was defined as ACR > 2.0 mg/mmol . PAD was defined as an ankle-brachial pressure index below 0.90 and /or a history of a peripheral arterial bypass or amputation . After 5 years of follow-up , 58 subjects had died ( 24 of cardiovascular causes ) . Both MA and PAD were associated with a 4-fold increase in cardiovascular mortality . After adjusting for age , sex , diabetes mellitus , hypertension , levels of total and HDL-cholesterol and triglyceride , body mass index , smoking habits , and preexistent ischemic heart disease , the relative risks ( RR ) ( 95 % confidence intervals ) were 3.2 ( 1.3 to 8.1 ) for MA and 2.4 ( 0.9 to 6.1 ) for PAD . When both MA and PAD were included in the multivariate analysis , the RRs were 2.9 ( 1.1 to 7.3 ) for MA and 2.0 ( 0.7 to 5.7 ) for PAD . MA and PAD were both associated with an about 2-fold increase in all-cause mortality . The RRs of all-cause mortality associated with MA and PAD were about 4 times higher among hypertensive than among normotensive subjects . We conclude that both MA and PAD are associated with an increased risk of cardiovascular mortality . MA and PAD are mutually independent risk indicators . The associations of MA and PAD with all-cause mortality are somewhat weaker . They are more pronounced in the presence of hypertension than in its absence . These data suggest that MA affects mortality risk through a mechanism different from generalized atherosclerosis BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements . Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events BACKGROUND Few population -based studies have assessed relations between plasma or serum total homocysteine ( tHcy ) and all-cause mortality . OBJECTIVE Our goal was to study associations between plasma tHcy and all-cause , cardiovascular , and noncardiovascular mortality . DESIGN This was a prospect i ve cohort study of 2127 men and 2639 women aged 65 - 67 y in 1992 - 1993 when they were recruited as part of a population -based national cardiovascular screening program carried out in Hordal and County , Norway . RESULTS During a median of 4.1 y of follow-up , 162 men and 97 women died . A strong relation was found between plasma tHcy and all-cause mortality . The association was highly significant for noncardiovascular and for cardiovascular causes of death . In a comparison of individuals having tHcy concentrations of 9.0 - 11.9 , 12.0 - 14.9 , 15.0 - 19.9 , or > or = 20 micromol/L with individuals having a tHcy concentration < 9 micromol/L , adjusted mortality ratios were 1.4 , 1.9 , 2.3 , and 3.6 ( P for trend = 0.0002 ) for noncardiovascular and 1.3 , 2.1 , 2.6 , and 3.5 ( P for trend = 0.0002 ) for cardiovascular causes of death . A tHcy increment of 5 micromol/L was associated with a 49 % ( 95 % CI : 28 % , 72 % ) increase in all-cause mortality , a 50 % ( 95 % CI : 21 % , 85 % ) increase in cardiovascular mortality ( 121 deaths ) , a 26 % ( 95 % CI : -2 % , 63 % ) increase in cancer mortality ( 103 deaths ) , and a 104 % ( 95 % CI : 44 % , 289 % ) increase in noncancer , noncardiovascular mortality ( 33 deaths ) . CONCLUSION Plasma tHcy is a strong predictor of both cardiovascular and noncardiovascular mortality in a general population of 65 - 72-y-olds . These results should encourage studies of tHcy in a wider perspective than one confined to cardiovascular disease BACKGROUND Several , but not all , prospect i ve studies have shown that low folate intakes , low circulating folate concentrations , or high plasma total homocysteine ( tHcy ) concentrations are associated with an increased risk of coronary artery disease ( CAD ) . OBJECTIVE We examined the relations of both serum folate and serum tHcy concentrations with acute coronary events in middle-aged men from eastern Finl and who had no CAD at baseline . DESIGN In a population -based prospect i ve cohort study , 1027 men aged 46 - 64 y were examined in 1991 - 1993 as part of the Kuopio Ischaemic Heart Disease Risk Factor Study . During an average follow-up of 7.7 y ( 7900 person-years of follow-up ) , 114 acute coronary events were observed in 61 men who had no previous history of CAD ( n = 810 ) . RESULTS In a Cox model , compared with men whose serum folate concentrations were in the lowest tertile , those whose concentrations were in the highest tertile had a risk factor-adjusted relative risk of acute coronary events of 0.35 ( 95 % CI : 0.17 , 0.73 ; P = 0.005 ) . Serum tHcy concentrations were not significantly associated with the risk of acute coronary events ( for the highest tertile compared with the lowest , adjusted relative risk = 1.03 ; 95 % CI : 0.57 , 1.87 ; P = 0.932 ) . CONCLUSIONS The results of this prospect i ve cohort study do not support the hypothesis that a high circulating tHcy concentration is a risk factor for acute coronary events in a male population free of prior heart disease . However , they do suggest that moderate-to-high serum folate concentrations are associated with a greatly reduced incidence of acute coronary events BACKGROUND The objective of this study was to examine the association of Joint National Committee ( JNC-V ) blood pressure and National Cholesterol Education Program ( NCEP ) cholesterol categories with coronary heart disease ( CHD ) risk , to incorporate them into coronary prediction algorithms , and to compare the discrimination properties of this approach with other noncategorical prediction functions . METHODS AND RESULTS This work was design ed as a prospect i ve , single-center study in the setting of a community-based cohort . The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up . During the 12 years of follow-up , a total of 383 men and 227 women developed CHD , which was significantly associated with categories of blood pressure , total cholesterol , LDL cholesterol , and HDL cholesterol ( all P<.001 ) . Sex-specific prediction equations were formulated to predict CHD risk according to age , diabetes , smoking , JNC-V blood pressure categories , and NCEP total cholesterol and LDL cholesterol categories . The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used . After adjustment for other factors , approximately 28 % of CHD events in men and 29 % in women were attributable to blood pressure levels that exceeded high normal ( > or = 130/85 ) . The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ( > or = 200 mg/dL ) was 27 % in men and 34 % in women . CONCLUSIONS Recommended guidelines of blood pressure , total cholesterol , and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample . A simple coronary disease prediction algorithm was developed using categorical variables , which allows physicians to predict multivariate CHD risk in patients without overt CHD Key Summary Points Risk prediction models are statistical models used to predict the probability of an outcome on the basis of the values of 1 or more risk factors ( markers ) . The accuracy of the model 's predictions is typically summarized with statistics that describe the model 's discrimination and calibration . Risk stratification tables are a more informative way to assess and compare the models . The tables illustrate the distribution of predictions across risk categories . That illustration allows users to assess 3 key measures of the models ' value for guiding medical decisions : the models ' calibration , ability to stratify people into clinical ly relevant risk categories , and accuracy at classifying patients into higher- and lower-risk categories . This information is contained in the margins of the risk stratification table rather than in its cells . The tables should only be used to compare risk prediction models when one of the models contains all of the markers that are contained in the other ( nested models ) ; they should not be used to compare models with different sets of markers ( nonnested models ) . The table predictions require corrections when casecontrol data are used . The recent epidemiologic and clinical literature is filled with studies evaluating statistical models that predict risk for disease or some other adverse event ( 15 ) . Because risk prediction models are intended to help patients and clinicians make decisions , evaluation of these models requires methods that differ from those used to assess models describing disease etiology . This is because the characteristics of the models are less important than their value for guiding decisions . Cook and colleagues ( 1 , 6 ) recently proposed a new approach to evaluate risk prediction models : a risk stratification table . This methodology appropriately focuses on the key purpose of a risk prediction model , which is to classify individuals into clinical ly relevant risk categories , and it has therefore been widely adopted in the literature ( 24 ) . We examine the risk stratification approach in detail in this article , identifying the relevant information that can be abstract ed from a risk stratification table and caution ing against misuses of the method that frequently occur in practice . We use a recently published study of a breast cancer risk prediction model by Tice and colleagues ( 2 ) to illustrate the concepts . Background A risk prediction marker is any measure that is used to predict a person 's risk for an event . It may be a quantitative measure , such as high-density lipoprotein cholesterol level , or a qualitative measure , such as family history of disease . Risk predictors are also risk factors , in the sense that they will necessarily be strongly associated with the risk for disease . But a large , significant association does not assure that the marker has value in predicting risk for many people . A risk prediction model is a statistical model that combines information from several markers . Common types include logistic regression models , Cox proportional hazard models , and classification trees . Each type of model produces a predicted risk for each person by using information in the model . Consider , for example , a model predicting breast cancer risk that includes age as the only predictor . The result ing risk prediction for a woman of a given age is simply the proportion of women her age who develop breast cancer . The woman 's predicted risk will change if more information is included in the model . For instance , if family history information is added , her predicted risk will be the proportion of women her age and with her family history who develop breast cancer . The purpose of a risk prediction model is to accurately stratify individuals into clinical ly relevant risk categories . This risk information can be used to guide clinical or policy decisions , for example , about preventive interventions for persons or disease screening for sub population s identified as high risk , or to select persons for inclusion in clinical trials . The value of a risk prediction model for guiding these kinds of decisions can be judged by the extent to which the risk calculated from the model reflects the fraction of persons in the population with actual events ( its calibration ) ; the proportions in which the population is stratified into clinical ly relevant risk categories ( its stratification capacity ) ; and the extent to which participants with events are assigned to high-risk categories and those without events are assigned to low-risk categories ( its classification accuracy ) . Risk prediction models are commonly evaluated by using the receiver-operating characteristic ( ROC ) curve ( 4 , 7 ) , which is a st and ard tool for evaluating the discriminatory accuracy of diagnostic or screening markers . This curve shows the true-positive rate plotted against the false-positive rate for rules that classify persons by using risk thresholds that vary over allpossible values . Receiver-operating characteristic curves are generally not helpful for evaluating risk prediction models because they do not provide information about the actual risks that the models predict or about the proportion of participants who have high or low risk values . Moreover , when comparing ROC curves for 2 risk prediction models , the models are aligned according to their false-positive rates ( that is , different risk thresholds are applied to the 2 models to achieve the same false-positive rate ) . This is clearly inappropriate . In addition , the area under the ROC curve or c-statistic , a commonly reported summary measure that can be interpreted as the probability that the predicted risk for a participant with an event is higher than that for a participant without an event , has little direct clinical relevance . Clinicians are never asked to compare risks for a pair of patients one who will eventually have the event and one who will not . Neither the ROC curve nor the c-statistic relates to the practical task of predicting risks for clinical decision making . Cook and colleagues ( 1 , 6 ) propose using risk stratification tables to evaluate the incremental value of a new marker , or the benefit of adding a new marker ( for example , C-reactive protein ) , to an established set of risk predictors ( for example , Framingham risk predictors , such as age , diabetes , cholesterol level , smoking , and low-density lipoprotein cholesterol levels ) . In these stratification tables , risks calculated from models with and without the new marker are cross-tabulated . This approach represents a substantial improvement over the use of ROC methodology because it displays the risks calculated by use of the model and the proportions of individuals in the population who are stratified into the risk groups . We will provide an example of this approach and show how information about model calibration , stratification capacity , and classification accuracy can be derived from a risk stratification table and used to assess the added value of a marker for clinical and health care policy decisions . Example Tice and colleagues ( 2 ) published a study that builds and evaluates a model for predicting breast cancer risk by using data from 1095484 women in a prospect i ve cohort and incidence data from the Surveillance , Epidemiology , and End Results data base . Age , race or ethnicity , family history , and history of breast biopsy were used to model risk with a Cox proportional hazard model . The study focused on the benefit of adding breast density information to the model . The hazard ratio for breast density in the multivariate model ( extremely dense vs. almost entirely fat ) was estimated as 4.2 for women younger than age 65 years and 2.2 for women age 65 years or older . This suggests that breast density is strongly associated with disease riskthat is , that breast cancer rates are higher among women with higher breast density . However , it does not describe the value of breast density for helping women make informed clinical decisions , which requires knowledge of the frequency distribution of breast density in the population . To evaluate the added value of breast density , Tice and colleagues defined 5-year breast cancer risk categories as low ( # # lt##1 % ) , low to intermediate ( 1 % to 1.66 % ) , intermediate to high ( 1.67 % to 2.5 % ) , and high ( # # gt##2.5 % ) . The 1.67 % cutoff for intermediate risk was presumably chosen on the basis of recommendations by the American Society of Clinical Oncology ( 8) and the Canadian Task Force on Preventive Health Care ( 9 ) to counsel women with 5-year risks greater than this threshold about considering tamoxifen for breast cancer prevention . Tice and colleagues used a risk stratification table ( Table 1 ) to compare risk prediction models with and without breast density . Table 1 . Five-Year Risks for Breast Cancer as Predicted by Models That Do and Do Not Include Breast Density Calibration Assessing model calibration is an important first step in evaluating any risk prediction model . Good calibration is essential ; it means that the model-predicted probability of an event for a person with specified predictor values is the same as or very close to the proportion of all persons in the population with those same predictor values who experience the event ( 10 ) . With many predictors , and especially with continuous predictors , we can not evaluate calibration at each possible predictor value because there are too few participants with exactly those values . Instead , the st and ard approach is to place persons within categories of predicted risk and to compare the category values with the observed event rates for participants in each category . The calibration of the risk prediction models for breast cancer can be assessed by comparing the proportions of events in the margins of Table 1 with the corresponding row and column labels . For the model without breast density , the proportions of observed events within each risk category are in the far-right Total column and they generally agree BACKGROUND Sinking prebeta lipoprotein is a putative marker for elevated levels of lipoprotein ( a ) . Although prospect i ve data suggest that increased plasma lipoprotein ( a ) is an independent risk factor for coronary heart disease in men , no prospect i ve studies are available in women . METHODS AND RESULTS From 1968 through 1975 , sinking prebeta lipoprotein was determined by paper electrophoresis in 3103 women Framingham Heart Study participants who were free of prevalent cardiovascular disease . A sinking prebeta lipoprotein b and was detectable in 434 of the women ( 14 % ) studied . The median follow-up interval was approximately 12 years . Incident cardiovascular disease was associated with b and presence using a proportional hazards model that included age , smoking , body mass index , systolic blood pressure , glucose intolerance , low- and high-density lipoprotein cholesterol , and ECG left ventricular hypertrophy . Multivariable adjusted relative risk estimates ( with 95 % confidence intervals ) for outcomes in the b and present versus absent groups were as follows : myocardial infa rct ion ( 82 events ) , 2.37 ( 1.48 to 3.81 ) ; intermittent claudication ( 62 events ) , 1.94 ( 1.07 to 3.50 ) ; cerebrovascular disease ( 83 events ) , 1.88 ( 1.12 to 3.15 ) ; total coronary heart disease ( 174 events ) , 1.61 ( 1.13 to 2.29 ) ; and total cardiovascular disease ( 305 events ) , 1.44 ( 1.09 to 1.91 ) . A subset analysis indicated that b and presence was 50.9 % sensitive and 95.4 % specific for detecting plasma lipoprotein ( a ) levels of > 30 mg/dL , the threshold value linked to increased cardiovascular disease risk in men . CONCLUSIONS Sinking prebeta lipoprotein was a valid surrogate for elevated lipoprotein ( a ) levels in Framingham Heart Study women . B and presence and , equivalently , elevated plasma lipoprotein ( a ) , was a strong , independent predictor of myocardial infa rct ion , intermittent claudication , and cerebrovascular disease . Confirmation of these findings in other longitudinal studies of women is needed BACKGROUND C-reactive protein ( CRP ) predicts risk of myocardial infa rct ion ( MI ) and stroke among apparently healthy men , but in women , virtually no data are available . METHODS AND RESULTS CRP was measured in baseline blood sample s from 122 apparently healthy participants in the Women 's Health Study who subsequently suffered a first cardiovascular event and from 244 age- and smoking-matched control subjects who remained free of cardiovascular disease during a 3-year follow-up period . Women who developed cardiovascular events had higher baseline CRP levels than control subjects ( P=0.0001 ) , such that those with the highest levels at baseline had a 5-fold increase in risk of any vascular event ( RR=4.8 ; 95 % CI , 2.3 to 10.1 ; P=0.0001 ) and a 7-fold increase in risk of MI or stroke ( RR=7.3 ; 95 % CI , 2.7 to 19.9 ; P=0.0001 ) . Risk estimates were independent of other risk factors , and prediction models that included CRP provided a better method to predict risk than models that excluded CRP ( all P values < 0.01 ) . In stratified analyses , CRP was a predictor among subgroups of women with low as well as high risk as defined by other cardiovascular risk factors . CONCLUSIONS In these prospect i ve data among women , CRP is a strong independent risk factor for cardiovascular disease that adds to the predictive value of risk models based on usual factors alone . ( Circulation . 1998;98:731 - 733 . OBJECTIVES We sought to determine the relative strength of high-sensitivity C-reactive protein ( hs-CRP ) and lipid levels as markers for future ischemic stroke compared with coronary heart disease ( CHD ) in women . BACKGROUND Although hs-CRP and lipid levels are established risk determinants for vascular disease , the relative strength of these biomarkers for ischemic stroke compared with CHD is uncertain . METHODS Among 15,632 initially healthy women who were followed for a 10-year period , we compared hs-CRP , total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , non-high-density lipoprotein cholesterol ( non-HDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , apolipoproteins A-I and B100 , and lipid ratios as determinants of ischemic stroke compared with CHD . RESULTS After adjustment for age , smoking status , blood pressure , diabetes , and obesity , the hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for the third versus the first tertile for future ischemic stroke compared with CHD were , respectively , 1.91 ( 95 % CI 1.13 to 3.21 ) and 2.26 ( 95 % CI 1.64 to 3.12 ) for TC , 1.29 ( 95 % CI 0.83 to 2.02 ) and 2.09 ( 95 % CI 1.53 to 2.85 ) for LDL-C , 0.57 ( 95 % CI 0.36 to 0.92 ) and 0.38 ( 95 % CI 0.27 to 0.52 ) for HDL-C , 1.72 ( 95 % CI 1.03 to 2.86 ) and 2.93 ( 95 % CI 2.04 to 4.21 ) for non-HDL-C , and 2.76 ( 95 % CI 1.51 to 5.05 ) and 1.66 ( 95 % CI 1.17 to 2.34 ) for hs-CRP . Of the lipid ratios , that of TC to HDL-C had the largest HR for both future ischemic stroke and CHD ( HR 1.95 [ 95 % CI 1.16 to 3.26 ] and 4.20 [ 95 % CI 2.79 to 6.32 ] , respectively ) . CONCLUSIONS In this large prospect i ve cohort of initially healthy women , lipid levels are significant risk determinants for ischemic stroke , but with a magnitude of effect smaller than that observed for CHD . High-sensitivity CRP associates more closely with ischemic stroke than with CHD . Concomitant evaluation of lipid levels and hs-CRP may improve risk assessment for stroke as well as CHD . ( The Women 's Health Study ; http://www . clinical trials.gov/ct/show/NCT00000479/ ; NCT00000479 ) INTRODUCTION Measurement of C-reactive protein ( CRP ) levels has been proposed as a useful marker to improve the prediction of future coronary artery disease ( CAD ) risk , but this notion has been challenged recently . METHODS AND RESULTS We performed a prospect i ve case-control study among apparently healthy men and women . The odds ratio ( OR ) for future CAD incidence was 2.49 ( 95 % CI=2.02 - 3.08 , p for linearity < 0.0001 ) unadjusted , and 1.66 ( 95 % CI=1.31 - 2.12 , p for linearity < 0.0001 ) , after adjustment for classical cardiovascular risk factors , for top versus bottom quartile of the CRP distribution . Notably , the risk factor adjusted predictive value was substantially stronger for fatal CAD ( OR=2.92 , 95 % CI=1.83 - 4.67 , p for linearity < 0.0001 ) than for non-fatal CAD ( OR=1.25 , 95 % CI=0.93 - 1.66 , p for linearity=0.06 ) . CRP levels were among the strongest predictors of CAD incidence and mortality . CRP levels remained a statistically significant predictor of future CAD , even after adjustment for the Framingham risk score . CONCLUSIONS In this British cohort with risk factor levels representative of a contemporary Western population , CRP concentration was among the strongest predictors of CAD incidence and mortality . We suggest that current guidelines on CRP measurement in clinical practice should be based on contemporary and representative population We have examined the risk of subsequent ischemic heart disease ( IHD ) in men according to their initial fasting plasma glucose level in a prospect i ve cohort study ( Caerphilly Collaborative Study ) of 4860 middle aged men from South Wales and Bristol , U.K. Ninety-four men reported themselves to be diabetic at initial screening and fasting venous plasma glucose levels were determined in these men and in a further 4519 non-diabetic men . At follow-up new IHD events occurred twice as commonly in diabetics compared to non-diabetics and overall mortality was increased 4-fold . Among non-diabetics however , increased IHD events only occurred in men with fasting values at the upper end of the distribution of baseline plasma glucose values [ at 6.8 mmol/l ( 122 mg/dl ) or more ] . This association was reduced , but remained statistically significant , after adjusting for factors associated with plasma glucose levels ; body mass index , plasma triglyceride , smoking habit and pre-existing IHD . In conclusion there is no evidence of a consistent , grade d increase in risk of IHD by initial fasting plasma glucose level although the risk is significantly increased in men with baseline plasma values at 6.8 mmol/l ( 122 mg/dl ) or more , and also in diabetics . This study suggests that such levels probably represent a pre-diabetic state in many individuals . Appropriate non-pharmacological intervention may be useful in halting the progression to the diabetic state , although this should be tested in experimental studies Lipoprotein(a ) [ Lp(a ) ] is formed by the assembly of LDL particles and a carbohydrate-rich protein , apolipoprotein(a ) [ apo(a ) ] , which has a high degree of structural homology with plasminogen . While the majority of retrospective studies have found an association between Lp(a ) level and cardiovascular disease ( CVD ) , the few prospect i ve studies to date have reported contradictory results . We conducted a nested case-control study using the participants in the Stanford Five-City Project , a long-term CVD prevention trial . Participants with an incident possible or definite myocardial infa rct ion or coronary death were matched to a single control subject for age , sex , ethnicity , residence in a treatment or control city , and time of survey . This process yielded 134 case-control pairs , 90 male and 44 female , for whom plasma was available for analysis of Lp(a ) . Lp(a ) values in nanomoles per liter were determined by an enzyme-linked immunoassay that measures Lp(a ) independently of apo(a ) size polymorphism . Apo(a ) size isoforms were determined by SDS-agarose gel electrophoresis . Median Lp(a ) level in male cases was almost double that in control subjects ( 41.8 versus 21.2 nmol/L ; P < .01 ) ; in female cases , median Lp(a ) was 34 % higher than in control subjects ( 32.5 versus 21.2 nmol/L ) , but this difference was not statistically significant . Among the male cases , there was an increased frequency of small apo(a ) isoforms , while no significant difference was found in apo(a ) size between female cases and control subjects . The association between Lp(a ) level and case-control status in men was independent of total , HDL , and non-HDL cholesterol levels , as well as apo(a ) size isoform , cigarette smoking , blood pressure , and obesity . In men , the most efficient threshold value of Lp(a ) concentration for separating cases and control subjects was 35 nmol/L ; the odds ratio for being a case above this level compared with below was 2.84 ( 95 % confidence interval : 1.53 - 5.27 , P < .001 ) . This study provides strong evidence that Lp(a ) level is a prospect i ve , independent risk factor for developing coronary artery disease in men and indicates that the size of apo(a ) may also play a role . The lack of a significant association in women deserves further evaluation in larger studies BACKGROUND Experimental studies have suggested both atherogenic and thrombogenic properties of lipoprotein(a ) [ Lp(a ) ] , depending on Lp(a ) plasma concentrations and varying antifibrinolytic capacity of apolipoprotein(a ) [ apo(a ) ] isoforms . Epidemiological studies may contribute to assessment of the relevance of these findings in the general population . METHODS AND RESULTS This study prospect ively investigated the association between Lp(a ) plasma concentrations , apo(a ) phenotypes , and the 5-year progression of carotid atherosclerosis assessed by high-resolution duplex ultrasound in a r and om sample population of 826 individuals . We differentiated early atherogenesis ( incident nonstenotic atherosclerosis ) from advanced ( stenotic ) stages in atherosclerosis that originate mainly from atherothrombotic mechanisms . Lp(a ) plasma concentrations predicted the risk of early atherogenesis in a dose-dependent fashion , with this association being confined to subjects with LDL cholesterol levels above the population median ( 3.3 mmol/L ) . Apo(a ) phenotypes were distributed similarly in subjects with and without early carotid atherosclerosis . In contrast , apo(a ) phenotypes of low molecular weight emerged as one of the strongest risk predictors of advanced stenotic atherosclerosis , especially when associated with high Lp(a ) plasma concentrations ( odds ratio , 6.4 ; 95 % CI , 2.8 to 14 . 9 ) . CONCLUSIONS Lp(a ) is one of the few risk factors capable of promoting both early and advanced stages of atherogenesis . Lp(a ) plasma concentrations predicted the risk of early atherogenesis synergistically with high LDL cholesterol . Low-molecular-weight apo(a ) phenotypes with a putatively high antifibrinolytic capacity in turn emerged as one of the leading risk conditions of advanced stenotic stages of atherosclerosis Background — Current guidelines suggest measuring high-sensitivity C-reactive protein ( hs-CRP ) as an aid to coronary risk assessment in adults without cardiovascular disease ( CVD ) . Whether other inflammatory biomarkers , such as fibrinogen , add further prognostic information is uncertain . Methods and Results — In a prospect i ve study of 27 742 initially healthy middle-aged women , the associations of baseline immunoassay fibrinogen and hs-CRP measurements with incident CVD were examined over a 10-year follow-up period . Compared with women in the bottom biomarker quintile , age-adjusted hazard ratios ( 95 % confidence intervals [ CIs ] ) for incident CVD for quintiles 2 to 5 of fibrinogen were 1.10 ( 0.86 to 1.41 ) , 1.30 ( 1.03 to 1.65 ) , 1.46 ( 1.16 to 1.85 ) , and 2.43 ( 1.95 to 3.02 ) ; for hs-CRP they were 1.48 ( 1.06 to 2.05 ) , 1.70 ( 1.24 to 2.33 ) , 2.20 ( 1.63 to 2.96 ) , and 3.24 ( 2.43 to 4.31 ) . After further adjustment for established risk factors , both biomarkers remained associated ( P for trend ≤0.001 ) with incident CVD ( hazard ratio , 1.35 ; 95 % CI , 1.07 to 1.71 for top fibrinogen quintile ; and hazard ratio , 1.68 ; 95 % CI , 1.22 to 2.29 for top hs-CRP quintile compared with the bottom quintiles ) . Further adjustment for the other biomarker result ed in hazard ratios of 1.23 and 1.56 ( P for trend=0.02 and 0.002 ) , respectively . Although fibrinogen correlated positively with hs-CRP ( rs=0.41 , P<0.001 ) , the highest CVD risk was associated with elevated levels of both fibrinogen and hs-CRP : age-adjusted hazard ratio of 3.45 ( 95 % CI , 2.60 to 4.57 ) for women with fibrinogen > 393 mg/dL and hs-CRP > 3 mg/L compared with < 329 mg/dL and < 1 mg/L , respectively . Conclusions — In this cohort of initially healthy women , baseline levels of fibrinogen measured with a high- quality immunoassay provided additive value to hs-CRP and traditional risk factors in predicting incident CVD CONTEXT Current guidelines for cardiovascular risk detection are controversial with regard to the clinical utility of different lipid measures , non-high-density lipoprotein cholesterol ( non-HDL-C ) , lipid ratios , apolipoproteins , and C-reactive protein ( CRP ) . OBJECTIVE To directly compare the clinical utility of total cholesterol , low-density lipoprotein cholesterol ( LDL-C ) , HDL-C , non-HDL-C , apolipoproteins A-I and B(100 ) , high-sensitivity CRP , and the ratios of total cholesterol to HDL-C , LDL-C to HDL-C , apolipoprotein B(100 ) to apolipoprotein A-I , and apolipoprotein B(100 ) to HDL-C as predictors of future cardiovascular events in women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 15,632 initially healthy US women aged 45 years or older ( interquartile range , 48 - 59 years ) who were enrolled between November 1992 and July 1995 . All participants were followed up over a 10-year period for the occurrence of future cardiovascular events . MAIN OUTCOME MEASURE Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for first-ever major cardiovascular events ( N = 464 ) according to baseline levels of each biomarker . RESULTS After adjustment for age , smoking status , blood pressure , diabetes , and body mass index , the HRs for future cardiovascular events for those in the extreme quintiles were 1.62 ( 95 % CI , 1.17 - 2.25 ) for LDL-C , 1.75 ( 95 % CI , 1.30 - 2.38 ) for apolipoprotein A-I , 2.08 ( 95 % CI , 1.45 - 2.97 ) for total cholesterol , 2.32 ( 95 % CI , 1.64 - 3.33 ) for HDL-C , 2.50 ( 95 % CI , 1.68 - 3.72 ) for apolipoprotein B(100 ) , 2.51 ( 95 % CI , 1.69 - 3.72 ) for non-HDL-C , and 2.98 ( 95 % CI , 1.90 - 4.67 ) for high-sensitivity CRP ( P<.001 for trend across all quintiles ) . The HRs for the lipid ratios were 3.01 ( 95 % CI , 2.01 - 4.50 ) for apolipoprotein B(100 ) to apolipoprotein A-I , 3.18 ( 95 % CI , 2.12 - 4.75 ) for LDL-C to HDL-C , 3.56 ( 95 % CI , 2.31 - 5.47 ) for apolipoprotein B(100 ) to HDL-C , and 3.81 ( 95 % CI , 2.47 - 5.86 ) for the total cholesterol to HDL-C ( P<.001 for trend across all quintiles ) . The correlation coefficients between high-sensitivity CRP and the lipid parameters ranged from -0.33 to 0.15 , and the clinical cut points for CRP of less than 1 , 1 to 3 , and higher than 3 mg/L provided prognostic information on risk across increasing levels of each lipid measure and lipid ratio . CONCLUSIONS Non-HDL-C and the ratio of total cholesterol to HDL-C were as good as or better than apolipoprotein fractions in the prediction of future cardiovascular events . After adjustment for age , blood pressure , smoking , diabetes , and obesity , high-sensitivity CRP added prognostic information beyond that conveyed by all lipid measures CONTEXT Atherosclerosis is often advanced before symptoms appear and it is not clear whether treatment is beneficial in middle-aged individuals with a low Framingham risk score ( FRS ) and mild to moderate sub clinical atherosclerosis . OBJECTIVE To assess whether statin therapy could slow progression and /or cause regression of carotid intima-media thickness ( CIMT ) over 2 years . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled study ( Measuring Effects on Intima-Media Thickness : an Evaluation of Rosuvastatin [ METEOR ] ) of 984 individuals , with either age ( mean , 57 years ) as the only coronary heart disease risk factor or a 10-year FRS of less than 10 % , modest CIMT thickening ( 1.2-<3.5 mm ) , and elevated LDL cholesterol ( mean , 154 mg/dL ) ; conducted at 61 primary care centers in the United States and Europe between August 2002 and May 2006 . INTERVENTION Participants received either a 40-mg dose of rosuvastatin or placebo . MAIN OUTCOME MEASURES Rate of change in maximum CIMT ( assessed with B-mode ultrasound ) for 12 carotid sites ; changes in maximum CIMT of the common carotid artery , carotid bulb , and internal carotid artery sites and in mean CIMT of the common carotid artery sites . CIMT regression was assessed in the rosuvastatin group only . RESULTS Among participants in the rosuvastatin group , the mean ( SD ) baseline LDL cholesterol level of 155 ( 24.1 ) mg/dL declined to 78 ( 27.5 ) mg/dL , a mean reduction of 49 % ( P<.001 vs placebo group ) . The change in maximum CIMT for the 12 carotid sites was -0.0014 ( 95 % CI , -0.0041 to 0.0014 ) mm/y for the rosuvastatin group vs 0.0131 ( 95 % CI , 0.0087 - 0.0174 ) mm/y for the placebo group ( P<.001 ) . The change in maximum CIMT for the rosuvastatin group was -0.0038 ( 95 % CI , -0.0064 to -0.0013 ) mm/y for the common carotid artery sites ( P<.001 ) , -0.0040 ( 95 % CI , -0.0090 to 0.0010 ) mm/y for the carotid bulb sites ( P<.001 ) , and 0.0039 ( 95 % CI , -0.0009 to 0.0088 ) mm/y for the internal carotid artery sites ( P = .02 ) . The change in mean CIMT for the rosuvastatin group for the common carotid artery sites was 0.0004 ( 95 % CI , -0.0011 to 0.0019 ) mm/y ( P<.001 ) . All P values are vs placebo group . Overall , rosuvastatin was well tolerated with infrequent serious adverse cardiovascular events ( 6 participants [ 0.86 % ] had 8 events [ 1.1 % ] over 2 years ) . CONCLUSIONS In middle-aged adults with an FRS of less than 10 % and evidence of sub clinical atherosclerosis , rosuvastatin result ed in statistically significant reductions in the rate of progression of maximum CIMT over 2 years vs placebo . Rosuvastatin did not induce disease regression . Larger , longer-term trials are needed to determine the clinical implication s of these findings . TRIAL REGISTRATION clinical trials.gov Identifier : Background —Accumulating data suggest a link between blood pressure and vascular inflammation . Methods and Results —We examined the relationship between blood pressure , C-reactive protein ( CRP ) , and incident first cardiovascular events among 15 215 women followed prospect ively over a median of 8.1 years . In cross-sectional analyses at baseline , median levels of CRP for women with blood pressure < 120/75 , 120 to 129/75 to 84 , 130 to 139/85 to 89 , 140 to 159/90 to 94 , and ≥160/95 mm Hg were 0.96 , 1.42 , 2.20 , 2.82 , and 3.34 mg/L , respectively ( P for trend < 0.0001 ) . Increasing categories of blood pressure were significant predictors of CRP levels at baseline . In prospect i ve analyses , both elevated CRP levels ( ≥3 mg/L ) and increasing categories of blood pressure were independent determinants of future cardiovascular events , and CRP had incremental prognostic value at all levels of blood pressure . The adjusted hazard ratio for women with blood pressure ≥160/95 mm Hg and CRP levels ≥3 mg/L was 8.31 ( 95 % CI , 4.44 to 15.55 , P < 0.0001 ) compared with those with blood pressure < 120/75 and CRP levels <3 mg/L. After participants had been divided into 4 groups on the basis of CRP levels ( <3 or ≥3 mg/L ) and blood pressure levels ( < 130/85 or ≥130/85 ) , the risk factor – adjusted hazard ratios were as follows : low CRP/low blood pressure , 1.0 ; high CRP/low blood pressure , 1.87 ( P = 0.002 ) ; low CRP/high blood pressure , 2.54 ( P < 0.0001 ) ; and high CRP/high blood pressure , 3.27 ( P < 0.0001 ) . Conclusions —CRP and blood pressure are independent determinants of cardiovascular risk , and their predictive value is additive Background —The Framingham Coronary Heart Disease ( CHD ) prediction score is recommended for global risk assessment in subjects prone to CHD . Recently , C-reactive protein ( CRP ) has emerged as an independent predictor of CHD . We sought to assess the potential of CRP measurements to enhance risk prediction based on the Framingham Risk Score ( FRS ) in a large cohort of middle-aged men from the general population . Methods and Results —We measured CRP and traditional cardiovascular risk factors at baseline in 3435 white men of German nationality , 45 to 74 years of age . All men were drawn from 3 r and om sample s of the general population in the Augsburg area located in Southern Germany in 1984 to 1985 , 1989 to 1990 , and 1994 to 1995 ( response rate , 80 % ) , and the FRS was calculated in all of them . Outcome was defined as nonfatal and fatal coronary events , including sudden cardiac death . During an average follow-up of 6.6 years , a total of 191 coronary events occurred . Cox regression showed a significant contribution of CRP to coronary event risk prediction independent of the FRS ( P = 0.0002 ) . In stratified analysis for 5 categories of FRS , CRP significantly added prognostic information to the FRS in subjects in 2 intermediate risk categories ( P = 0.03 and P = 0.02 ) . Conclusions —Our results suggest that CRP enhances global coronary risk as assessed by the FRS , especially in intermediate risk groups . This might have implication s for future risk assessment BACKGROUND Recent evidence implicates inflammation in the pathogenesis of coronary heart disease ( CHD ) . C-reactive protein , a plasma marker of inflammation , is a marker of CHD risk but has been studied in few prospect i ve investigations of the general population . METHODS AND RESULTS We prospect ively examined the association of CRP with incident CHD among middle-aged adults in the Atherosclerosis Risk In Communities ( ARIC ) study . With the use of a nested case-cohort approach , we measured CRP in stored , baseline blood sample s of 2 groups of subjects in whom CHD developed during follow-up ( 242 incident cases from 1987 to 1993 and 373 from 1990 to 1995 ) and , for comparison , 2 stratified r and om sample s of noncases . In analyses adjusted for demographic variables and traditional CHD risk factors , the relative risk of CHD across quintiles of CRP was 1.0 , 0.8 , 1.6 , 1.9 , and 1.5 for events from 1987 to 1995 ( P for trend = .01 ) . As expected , inclusion of fibrinogen , intracellular adhesion molecule-1 , and white blood cell count ( other potential markers of the inflammatory reaction ) attenuated the association of CRP with CHD incidence . In a supplemental cross-sectional analysis , CRP was not associated with carotid intima-media thickness after adjustment for major risk factors . CONCLUSIONS C-reactive protein is a moderately strong marker of risk of CHD in this cohort of middle-aged adults , consistent with the role of inflammation in the pathogenesis of CHD events . The association was not specific to CRP because other markers of inflammation could largely account for the finding OBJECTIVE Prospect i ve assessment of the risk of coronary heart disease associated with total serum homocyst(e)ine ( homocysteine ) concentration . DESIGN Nested case-control study . SETTING Caerphilly and surrounding villages in south Wales , UK . PARTICIPANTS 2290 men who participated in phase II of the study in 1984 . After a mean follow up of 10 years , 312 men developed coronary heart disease and were compared with 1248 r and omly selected , age frequency matched controls . MAIN OUTCOME MEASURE Acute myocardial infa rct ion or death from coronary heart disease . RESULTS The geometric mean serum homocysteine concentration was higher in cases ( 12.2 μmol/l , 95 % confidence interval ( CI ) 11.8 to 12.6 μmol/l ) than in controls ( 11.8 μmol/l , 95 % CI 11.3 to 12.5 μmol/l ) ( p = 0.09 ) . There was a grade d increase in the odds ratio of coronary heart disease across quintiles of the homocysteine concentration distribution compared with the first ( p = 0.04 ) , which was attenuated when adjusted for confounding variables ( p = 0.4 ) . There was a small but non-significant increase in the adjusted odds ratio of coronary heart disease per st and ard deviation change in the log distribution of homocysteine concentration ( OR = 1.07 ( 95 % CI .93 to 1.24 ) , p = 0.34 ) . Comparing the top quintile of the homocysteine concentration with the remaining 80 % , the adjusted odds ratio of coronary heart disease was 1.03 ( 95 % CI 0.73 to 1.45 ) ( p = 0.8 ) and comparing the top 5 % with the remaining 95 % it was 1.05 ( 95 % CI 0.56 to 1.95 ) ( p = 0.9 ) . CONCLUSIONS These findings do not support the hypothesis that a raised homocysteine concentration is a strong independent risk factor for coronary heart disease . R and omised controlled trials of homocysteine lowering treatment such as folic acid are needed before generalising the early positive results of observational studies Background —Elevated serum total homocysteine ( tHcy ) is an established risk factor for cardiovascular disease ( CVD ) , especially in men . However , there are few prospect i ve population studies on female cohorts , and none of these has been longer than 13 years . Methods and Results —The Population Study of Women in Gothenburg began in 1968/1969 , at which time a representative population -based cohort of women aged 38 , 46 , 50 , 54 , and 60 years was recruited . The present cohort is a prospect i ve follow-up of 1368 women in the original cohort for whom blood sample s were stored and who were free of previous acute myocardial infa rct ion ( AMI ) at the 1968/1969 baseline . Homocysteine was analyzed in 2001 with frozen serum from the baseline study and related to AMI incidence and mortality during 24 years of follow-up . Cox regression analyses were used with adjustment for age , traditional risk factors , and tHcy modifiers . For the fifth tHcy quintile , relative risk was 1.86 ( 95 % CI 1.06 to 3.26 ) for AMI and 5.14 ( 95 % CI 2.22 to 11.92 ) for death due to AMI . Age-st and ardized Kaplan-Meier plots for the fifth tHcy quintile versus others showed significant differences both for AMI and for death due to AMI that were apparent after 15 years of follow-up . Conclusions —Homocysteine in middle-aged women is an independent risk factor for myocardial infa rct ion and in particular mortality due to myocardial infa rct ion . The study illustrates that long-term prospect i ve studies might be necessary to show effects of homocysteine levels on AMI morbidity and mortality in women OBJECTIVE --To examine the association between the serum lipoprotein ( a ) concentration and subsequent coronary heart disease . DESIGN -- Prospect i ve case-control study based on a six year follow up of a general population sample of men aged 50 at baseline in 1983 - 4 . Serum sample s were frozen at the time of the baseline examination and kept at -70 degrees C for six years , after which the lipoprotein ( a ) concentrations in the sample s were measured in cases and controls . SETTING --City of Gothenburg , Sweden . SUBJECTS--26 Men , from a general population sample of 776 men , who had sustained a myocardial infa rct ion or died of coronary heart disease during the six years and 109 r and omly selected controls from the same sample who had remained free of myocardial infa rct ion . In neither cases nor controls was there a history of myocardial infa rct ion at baseline . MAIN OUTCOME MEASURES --Proportion of myocardial infa rct ion or deaths from coronary heart disease , or both , in relation to the serum lipoprotein ( a ) concentration . RESULTS --Men who suffered coronary heart disease had significantly higher serum lipoprotein ( a ) concentrations than controls ( mean difference 105 mg/l ; 95 % confidence interval 18 to 192 mg/l ) . Men with the highest fifth of serum lipoprotein ( a ) concentrations ( cut off point 365 mg/l ) suffered a coronary heart disease rate which was more than twice that of men with the lowest four fifths of concentrations . Logistic regression analysis showed the serum lipoprotein ( a ) concentration to be significantly associated with coronary heart disease independently of other risk factors . CONCLUSION --The serum lipoprotein ( a ) concentration in middle aged men is an independent risk factor for subsequent myocardial infa rct ion or death from coronary heart disease OBJECTIVE To assess prospect ively the risk of coronary heart disease associated with elevated plasma levels of homocyst(e)ine . DESIGN Nested case-control study using prospect ively collected blood sample s. SETTING Participants in the Physicians ' Health Study . PARTICIPANTS A total of 14,916 male physicians , aged 40 to 84 years , with no prior myocardial infa rct ion ( MI ) or stroke provided plasma sample s at baseline and were followed up for 5 years . Sample s from 271 men who subsequently developed MI were analyzed for homocyst(e)ine levels together with paired controls , matched by age and smoking . MAIN OUTCOME MEASURE Acute MI or death due to coronary disease . RESULTS Levels of homocyst(e)ine were higher in cases than in controls ( 11.1 + /- 4.0 [ SD ] vs 10.5 + /- 2.8 nmol/mL ; P = .03 ) . The difference was attributable to an excess of high values among men who later had MIs . The relative risk for the highest 5 % vs the bottom 90 % of homocyst(e)ine levels was 3.1 ( 95 % confidence interval , 1.4 to 6.9 ; P = .005 ) . After additional adjustment for diabetes , hypertension , aspirin assignment , Quetelet 's Index , and total/high-density lipoprotein cholesterol , this relative risk was 3.4 ( 95 % confidence interval , 1.3 to 8.8 ) ( P = .01 ) . Thirteen controls and 31 cases ( 11 % ) had values above the 95th percentile of the controls . CONCLUSIONS Moderately high levels of plasma homocyst(e)ine are associated with subsequent risk of MI independent of other coronary risk factors . Because high levels can often be easily treated with vitamin supplements , homocyst(e)ine may be an independent , modifiable risk factor OBJECTIVES This study was undertaken to determine whether lipoprotein(a ) [ Lp(a ) ] is an independent risk factor for ischemic heart disease ( IHD ) and to establish the relation of Lp(a ) to the other lipid fractions . BACKGROUND Several , but not all , studies have shown that elevated Lp(a ) concentrations may be associated with IHD ; very few have been prospect i ve . METHODS A 5-year prospect i ve follow-up study was conducted in 2,156 French Canadian men 47 to 76 years old , without clinical evidence of IHD . Lipid measurements obtained at baseline included total cholesterol , low density lipoprotein ( LDL ) cholesterol , high density lipoprotein ( HDL ) cholesterol , apoprotein B and Lp(a ) . During the follow-up period , there were 116 first IHD events ( myocardial infa rct ion , angina , death ) . Adjusted proportional hazards models were used to estimate the relative risk for the different variables . The cohort was also classified according to Lp(a ) levels and other lipid risk factor tertiles to evaluate the relation of elevated Lp(a ) levels to these risk factors . A cutoff value of 30 mg/dl was used for Lp(a ) . Risk ratios were calculated using the group with low Lp(a ) levels and the first tertile of lipid measures as a reference . RESULTS Lp(a ) was not an independent risk factor for IHD but seemed to increase the deleterious effects of mildly elevated LDL cholesterol and elevated total cholesterol and apoprotein B levels and seemed to counteract the beneficial effects associated with elevated HDL cholesterol levels . CONCLUSIONS In this cohort , Lp(a ) was not an independent risk factor for IHD but appeared to increase the risk associated with other lipid risk factors OBJECTIVE The prognostic implication s of carotid plaque calcification ( CPC ) relative to subsequent vascular events are unclear . Our aim was to determine the association between CPC and risk of vascular events in a prospect i ve multi-ethnic cohort . METHODS CPC was assessed among 1118 stroke-free subjects ( mean age 68+/-8 years ; 59 % women ; 59 % Hispanic , 22 % black , 19 % white ) from the Northern Manhattan Study using high-resolution B-mode ultrasound . CPC was defined by presence of any acoustic shadowing associated with carotid plaque , producing a reduction in echo amplitude due to intervening structures with high attenuation . Using Cox proportional hazards models , hazard ratios ( HR ) were estimated for the combined vascular outcome , defined as ischemic stroke ( IS ) , myocardial infa rct ion ( MI ) or vascular death ( VD ) . RESULTS Carotid plaque was present in 637 ( 57 % ) subjects . CPC was present in 225 subjects ( 20 % of total cohort ; 35 % of those with plaque ) . During a mean follow-up time of 2.7 years , the combined vascular outcome occurred among 52 subjects ( 20 IS , 22 MI , and 24 VD ) . Adjusting for demographics , major vascular risk factors , and carotid intima media thickness , those with CPC ( in comparison to those without plaque ) had a significantly increased risk of the combined vascular outcome ( HR 2.5 , 95 % CI 1.0 - 5.8 ) . CONCLUSIONS In this population -based cohort , the presence of calcified carotid plaque , as assessed by high-resolution B-mode ultrasound , was an independent predictor of vascular events . It may serve as a simple and non-invasive marker of increased atherosclerotic risk and further aid in vascular risk stratification As ultrasonographically assessed carotid arteriosclerosis is being used as a surrogate measure for coronary arteriosclerosis , we performed a prospect i ve longitudinal study of the association of our high-resolution ultrasound assessment of extracranial carotid morphology with the risk of acute coronary events in 1,288 eastern Finnish men . The presence of any structural changes in the common carotid arteries or carotid bulbs was associated with a 3.29-fold ( 95 % confidence interval , 1.31 - 8.29 ; p = 0.0074 ) , intimal-medial thickening with a 2.17-fold ( 95 % confidence interval , 0.70 - 6.74 ; p = NS ) , small carotid plaques with a 4.15-fold ( 95 % confidence interval , 1.51 - 11.47 ; p less than 0.01 ) , and large ( " stenotic " ) plaques with a 6.71-fold ( 95 % confidence interval , 1.33 - 33.91 ; p less than 0.01 ) risk of acute myocardial infa rct ion compared with men free of any structural changes in the carotid artery wall at baseline . These data confirm the close relation between carotid artery wall morphology and coronary heart disease Besides the accepted major risk factors for myocardial infa rct ion ( MI ) , cholesterol , hypertension and smoking , several other variables such as lipoproteins , apolipoproteins , fibrinogen and family history of MI , have been considered , but their usefulness as predictors of MI is controversially discussed . The Göttingen Risk Incidence and Prevalence Study ( GRIPS ) aim ed to evaluate the independent impact of the latter in comparison to the established risk factors . GRIPS is a prospect i ve cohort study , which included 5790 men , aged 40 - 59.9 years , without cardiovascular disease at baseline . Multivariate logistic regression models for the estimation of the MI risk based on the 10-year follow-up data from 97.4 % of the study participants established LDL cholesterol as the strongest predictor of MI . It was followed by family history of MI , Lp(a ) , age , smoking , systolic blood pressure , HDL cholesterol ( inversely related ) and plasma glucose ( P < 0.001 ) . Apolipoprotein B as well as the ratios total/HDL cholesterol , LDL/HDL cholesterol and Apo B/AI were less effective predictors than LDL cholesterol and did not contribute independently to the estimation of MI risk . Similarly apoprotein AI was a weaker predictor of MI risk then HDL cholesterol . GRIPS is the first prospect i ve cohort study which clearly justifies the key role of LDL cholesterol in preventive strategies . However , the data also give strong support for the additional consideration of other risk factors for a valid estimation of the MI risk for an individual subject OBJECTIVE To further establish the importance of total plasma apolipoprotein A-I and lipoprotein(a ) in the prediction of primary acute myocardial infa rct ion ( AMI ) in men . DESIGN An incident case-control study . SETTING The study was nested within the Västerbotten Intervention Program ( VIP ) and the Northern Sweden MONICA cohorts . SUBJECTS A total of 62 male AMI cases and 124 matched controls , r and omly selected from the study cohorts . RESULTS In multivariate logistic regression , significant odds ratios ( OR ) were found for Lp(a ) above 200 mg L-1 , apo A-I below the mean value ( 1136 mg L-1 ) and total cholesterol ( TC ) above 7.8 mmol L-1 . TC interacted significantly with Lp(a ) ; for Lp(a ) above 200 mg L-1 and TC below 6.5 mmol L-1 , OR = 5.6 ; for Lp(a ) above 200 mg L-1 and TC above 6.5 mmol L-1 , OR = 12.6 . To evaluate the potential effect of reducing high levels of Lp(a ) or TC on the incidence of AMI in males , the attributable risk percentage ( ARP ) was calculated when interaction between the two variables was present . ARP is 31 % for Lp(a ) and 21 % for TC , implying that 31 % of the cases are due to high Lp(a ) and 21 % of the cases are due to high TC levels . CONCLUSIONS In the Swedish male population , total apo A-I in plasma is a protective factor and a plasma Lp(a ) level above 200 mg L-1 is a risk factor for AMI in males . A TC level above 6.5 mmol L-1 increased the risk of AMI if the Lp(a ) level was above 200 mg L-1 , suggesting Lp(a ) to be useful in identifying high risk individuals needed to be treated OBJECTIVES We sought to prospect ively assess whether self-reported periodontal disease is associated with subsequent risk of cardiovascular disease in a large population of male physicians . BACKGROUND Periodontal disease , the result of a complex interplay of bacterial infection and chronic inflammation , has been suggested to be a predictor of cardiovascular disease . METHODS Physicians ' Health Study I was a r and omized , double-blind , placebo-controlled trial of aspirin and beta-carotene in 22,071 U.S. male physicians . A total of 22,037 physicians provided self-reports of presence or absence of periodontal disease at study entry and were included in this analysis . RESULTS A total of 2,653 physicians reported a personal history of periodontal disease at baseline . During an average of 12.3 years of follow-up , there were 797 nonfatal myocardial infa rct ions , 631 nonfatal strokes and 614 cardiovascular deaths . Thus , for each end point , the study had > 90 % power to detect a clinical ly important increased risk of 50 % . In Cox proportional hazards regression analysis adjusted for age and treatment assignment , physicians who reported periodontal disease at baseline had slightly elevated , but statistically nonsignificant , relative risks ( RR ) of nonfatal myocardial infa rct ion , ( RR , 1.12 ; 95 % confidence interval [ CI ] , 0.92 to 1.36 ) , nonfatal stroke ( RR , 1.10 ; CI , 0.88 to 1.37 ) and cardiovascular death ( RR , 1.20 ; CI , 0.97 to 1.49 ) . Relative risk for a combined end point of all important cardiovascular events ( first occurrence of nonfatal myocardial infa rct ion , nonfatal stroke or cardiovascular death ) was 1.13 ( CI , 0.99 to 1.28 ) . After adjustment for other cardiovascular risk factors , RRs were all attenuated and nonsignificant . CONCLUSIONS These prospect i ve data suggest that self-reported periodontal disease is not an independent predictor of subsequent cardiovascular disease in middle-aged to elderly men BACKGROUND Coronary artery calcium ( CAC ) and carotid intima-media thickness ( IMT ) are noninvasive measures of atherosclerosis that consensus panels have recommended as possible additions to risk factor assessment for predicting the probability of cardiovascular disease ( CVD ) occurrence . Our objective was to assess whether maximum carotid IMT or CAC ( Agatston score ) is the better predictor of incident CVD . METHODS A prospect i ve cohort study of subjects aged 45 to 84 years in 4 ethnic groups , who were initially free of CVD ( n = 6698 ) was performed , with st and ardized carotid IMT and CAC measures at baseline , in 6 field centers of the Multi-Ethnic Study of Atherosclerosis ( MESA ) . The main outcome measure was the risk of incident CVD events ( coronary heart disease , stroke , and fatal CVD ) over a maximum of 5.3 years of follow-up . RESULTS There were 222 CVD events during follow-up . Coronary artery calcium was associated more strongly than carotid IMT with the risk of incident CVD . After adjustment for each other ( CAC score and IMT ) and age , race , and sex [ corrected ] , the hazard ratio of CVD increased 2.1-fold ( 95 % confidence interval [ CI ] , 1.8 - 2.5 ) for each 1-st and ard deviation ( SD ) increment of log-transformed CAC score , vs 1.3-fold ( 95 % CI , 1.1 - 1.4 ) for each 1-SD increment of the maximum IMT . For coronary heart disease , the hazard ratios per 1-SD increment increased 2.5-fold ( 95 % CI , 2.1 - 3.1 ) for CAC score and 1.2-fold ( 95 % CI , 1.0 - 1.4 ) for IMT . A receiver operating characteristic curve analysis also suggested that CAC score was a better predictor of incident CVD than was IMT , with areas under the curve of 0.81 vs 0.78 , respectively . CONCLUSION Although whether and how to clinical ly use bioimaging tests of sub clinical atherosclerosis remains a topic of debate , this study found that CAC score is a better predictor of subsequent CVD events than carotid IMT Few studies have determined whether carotid artery intima-media thickness ( IMT ) is associated prospect ively with risk of first ischemic stroke . In the Atherosclerosis Risk in Communities Study , carotid IMT , an index of generalized atherosclerosis , was defined as the mean of IMT measured by B-mode ultrasonography at six sites of the carotid arteries . The authors assessed the relation of mean IMT to stroke incidence over 6 - 9 years ' follow-up ( 1987 - 1995 ) among 7,865 women and 6,349 men aged 45 - 64 years without prior stroke at baseline in four US communities . There were 90 incident ischemic stroke events for women and 109 for men . In sex-specific Cox proportional hazards models adjusting only for age , race , and community , the hazard rate ratios comparing extreme mean IMT values ( > or = 1 mm ) to values less than 0.6 mm were 8.5 for women ( 95 % confidence interval : 3.5 , 20.7 ) and 3.6 for men ( 95 % confidence interval : 1.5 , 9.2 ) . The relation was grade d , and models with cubic splines indicated significant nonlinearity , with hazards increasing more rapidly at lower IMTs than at higher IMTs . Thus , models using linear IMT values substantially underestimate the strength of the association at lower IMTs . The strength of the association was reduced by the inclusion of putative stroke risk factors , but it remained elevated at higher IMTs . Hence , mean carotid IMT is a noninvasive predictor of future ischemic stroke incidence BACKGROUND Elevated plasma total homocysteine ( tHcy ) , low B-vitamin intake , and genetic polymorphisms related to tHcy metabolism may play roles in coronary heart disease ( CHD ) . More prospect i ve studies are needed . METHODS AND RESULTS We used a prospect i ve case-cohort design to determine whether tHcy-related factors are associated with incidence of CHD over an average of 3.3 years of follow-up in a biracial sample of middle-aged men and women . Age- , race- , and field center-adjusted CHD incidence was associated positively ( P<0.05 ) with tHcy in women but not men , and CHD was associated negatively ( P<0.05 ) with plasma folate ( women only ) , plasma pyridoxal 5'-phosphate ( both sexes ) , and vitamin supplementation ( women only ) . However , after accounting for other risk factors , only plasma pyridoxal 5'-phosphate was associated with CHD incidence ; the relative risk for the highest versus lowest quintile of pyridoxal 5'-phosphate was 0.28 ( 95 % CI=0.1 to 0.7 ) . There was no association of CHD with the C677 T mutation of the methylenetetrahydrofolate reductase gene or with 3 mutations of the cystathionine beta-synthase gene . CONCLUSIONS Our prospect i ve findings add uncertainty to conclusions derived mostly from cross-sectional studies that tHcy is a major , independent , causative risk factor for CHD . Our findings point more strongly to the possibility that vitamin B6 offers independent protection . R and omized trials , some of which are under way , are needed to better clarify the interrelationships of tHcy , B vitamins , and cardiovascular disease BACKGROUND Mild hyperhomocystinemia has been suggested as an indicator of an increased risk of cardiovascular disease . OBJECTIVE To examine whether serum homocysteine concentration is a predictor of coronary heart disease ( CHD ) events . METHODS A case-control study , nested in a population -based cohort study was used . During a follow-up of 13 years , 166 major coronary events ( death from CHD or nonfatal myocardial infa rct ion ) occurred in men with evidence of heart disease at baseline and 272 events in men without a history of heart disease . Two controls per case were selected by individual matching . RESULTS Among men with known heart disease at baseline , the relative risk ( 95 % confidence interval ) of CHD events adjusted for age , smoking , hypertension , diabetes mellitus , serum cholesterol level , body mass index , and alcohol consumption was 2.23 ( 95 % confidence interval , 1.03 - 4.85 ) in the highest serum homocysteine quintile compared with the lowest quintile . Among the men free of heart disease at baseline , the corresponding relative risk was 0.90 ( 95 % confidence interval , 0.51 - 1.60 ) . CONCLUSIONS This prospect i ve study does not support the hypothesis that a high concentration of serum homocysteine is a risk factor for coronary events in a population free of heart disease . However , it does suggest that mild hyperhomocystinemia predicts secondary coronary events in men with heart disease , possibly as a consequence of atherosclerotic changes BACKGROUND Recent trials have demonstrated better outcomes with intensive than with moderate statin treatment . Intensive treatment produced greater reductions in both low-density lipoprotein ( LDL ) cholesterol and C-reactive protein ( CRP ) , suggesting a relationship between these two biomarkers and disease progression . METHODS We performed intravascular ultrasonography in 502 patients with angiographically documented coronary disease . Patients were r and omly assigned to receive moderate treatment ( 40 mg of pravastatin orally per day ) or intensive treatment ( 80 mg of atorvastatin orally per day ) . Ultrasonography was repeated after 18 months to measure the progression of atherosclerosis . Lipoprotein and CRP levels were measured at baseline and follow-up . RESULTS In the group as a whole , the mean LDL cholesterol level was reduced from 150.2 mg per deciliter ( 3.88 mmol per liter ) at baseline to 94.5 mg per deciliter ( 2.44 mmol per liter ) at 18 months ( P<0.001 ) , and the geometric mean CRP level decreased from 2.9 to 2.3 mg per liter ( P<0.001 ) . The correlation between the reduction in LDL cholesterol levels and that in CRP levels was weak but significant in the group as a whole ( r=0.13 , P=0.005 ) , but not in either treatment group alone . In univariate analyses , the percent change in the levels of LDL cholesterol , CRP , apolipoprotein B-100 , and non-high-density lipoprotein cholesterol were related to the rate of progression of atherosclerosis . After adjustment for the reduction in these lipid levels , the decrease in CRP levels was independently and significantly correlated with the rate of progression . Patients with reductions in both LDL cholesterol and CRP that were greater than the median had significantly slower rates of progression than patients with reductions in both biomarkers that were less than the median ( P=0.001 ) . CONCLUSIONS For patients with coronary artery disease , the reduced rate of progression of atherosclerosis associated with intensive statin treatment , as compared with moderate statin treatment , is significantly related to greater reductions in the levels of both atherogenic lipoproteins and CRP Background —The South Bay Heart Watch is a prospect i ve cohort study design ed to appraise the value of coronary calcium and risk factors for predicting outcomes in asymptomatic adults . Two factors that may be related to subsequent cardiovascular events are coronary calcium ( CAC , a manifestation of sub clinical atherosclerosis ) and high-sensitivity C-reactive protein ( CRP , a measure of chronic inflammation ) . Methods and Results —Between December 1990 and December 1992 , 1461 participants without coronary heart disease underwent baseline risk factor screening , computed tomography for CAC , and measurement of CRP . Participants were followed up for 6.4±1.3 years . Cox regression analyses were conducted for the 967 nondiabetics with CRP levels ≤10 mg/L to estimate the risk-factor – adjusted relative risks of CAC and CRP for the occurrence of ( 1 ) nonfatal myocardial infa rct ion ( MI ) or coronary death and ( 2 ) any cardiovascular event ( MI , coronary death , coronary revascularization , or stroke ) . CAC was a predictor of both end points ( P < 0.005 ) , and CRP was a predictor of any cardiovascular event ( P = 0.03 ) . Risk group analysis defined by tertiles for CAC ( < 3.7 , 3.7 to 142.1 , > 142.1 ) and the 75th percentile for CRP ( > 4.05 mg/L ) indicated that there was increasing risk with increasing calcium and CRP . Relative risks for the medium-calcium/low-CRP risk group to high-calcium/high-CRP risk group ranged from 1.8 to 6.1 for MI/coronary death ( P = 0.003 ) and 2.8 to 7.5 for any cardiovascular event ( P < 0.001 ) . Conclusions — Participants without diabetes and those at intermediate risk may benefit from risk stratification based on high-sensitivity CRP levels and CAC , because both factors contribute independently toward the incidence of cardiovascular events Background and Purpose — The level of total homocysteine ( tHcy ) that confers a risk of ischemic stroke is unsettled , and no prospect i ve cohort studies have included sufficient elderly minority subjects . We investigated the association between mild to moderate fasting tHcy level and the incidence of ischemic stroke , myocardial infa rct ion , and vascular death in a multiethnic prospect i ve study . Methods — A population -based cohort was followed for vascular events ( stroke , myocardial infa rct ion , and vascular death ) . Baseline values of tHcy and methylmalonic acid were measured among 2939 subjects ( mean age , 69±10 ; 61 % women , 53 % Hispanics , 24 % blacks , and 20 % whites ) . Cox proportional models were used to calculate hazard ratios ( HRs ) and 95 % CIs in tHcy categories after adjusting for age , race , education , renal insufficiency , B12 deficiency , and other risk factors . Results — The adjusted HR for a tHcy level ≥15 μmol/L compared with < 10 μmol/L was greatest for vascular death ( HR=6.04 ; 95 % CI , 3.44 to 10.60 ) , followed by combined vascular events ( HR=2.27 ; 95 % CI , 1.51 to 3.43 ) , ischemic stroke ( HR=2.01 ; 95 % CI , 1.00 to 4.05 ) , and nonvascular death ( HR=2.02 ; 95 % CI , 1.31 to 3.14 ) . Mild to moderate elevations of tHcy of 10 to 15 μmol/L were not significantly predictive of ischemic stroke , but increased the risk of vascular death ( 2.27 ; 95 % CI , 1.44 to 3.60 ) and combined vascular events ( 1.42 ; 95 % CI , 1.06 to 1.88 ) . The effect of tHcy was stronger among whites and Hispanics , but not a significant risk factor for blacks . Conclusions — Total Hcy elevations above 15 μmol/L are an independent risk factor for ischemic stroke , whereas mild elevations of tHcy of 10 to 15 μmol/L are less predictive . The vascular effects of tHcy are greatest among whites and Hispanics , and less among blacks OBJECTIVES The purpose of this study was to determine the prognostic accuracy of electron beam computed tomographic ( CT ) scanning of the coronary arteries and the relationship of coronary calcification to st and ard coronary disease risk factors and C-reactive protein ( CRP ) in the prediction of atherosclerotic cardiovascular disease ( ASCVD ) events in apparently healthy middle-age persons . BACKGROUND As a screening test for coronary artery disease ( CAD ) , electron beam CT scanning remains controversial . METHODS In a prospect i ve , population -based study , 4,903 asymptomatic persons age 50 to 70 years underwent electron beam CT scanning of the coronary arteries . RESULTS At 4.3 years , follow-up was available in 4,613 participants ( 94 % ) , and 119 had sustained at least one ASCVD event . Subjects with ASCVD events had higher baseline coronary calcium scores ( median [ interquartile range ] , Agatston method ) than those without events : 384 ( 127 , 800 ) versus 10 ( 0 , 86 ) ( p < 0.0001 ) . For coronary calcium score threshold > or = 100 versus < 100 , relative risk ( 95 % confidence interval ) was 9.6 ( 6.7 to 13.9 ) for all ASCVD events , 11.1 ( 7.3 to 16.7 ) for all CAD events , and 9.2 ( 4.9 to 17.3 ) for non-fatal myocardial infa rct ion and death . The coronary calcium score predicted CAD events independently of st and ard risk factors and CRP ( p = 0.004 ) , was superior to the Framingham risk index in the prediction of events ( area under the receiver-operating characteristic curve of 0.79 + /- 0.03 vs. 0.69 + /- 0.03 , p = 0.0006 ) , and enhanced stratification of those falling into the Framingham categories of low , intermediate , and high risk ( p < 0.0001 ) . CONCLUSIONS The electron beam CT coronary calcium score predicts CAD events independent of st and ard risk factors , more accurately than st and ard risk factors and CRP , and refines Framingham risk stratification Background —Measuring C-reactive protein ( CRP ) has been recommended to identify patients at high risk for coronary heart disease ( CHD ) with low LDL cholesterol ( LDL-C ) . Lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) is a proinflammatory enzyme associated primarily with LDL . Methods and Results —In a prospect i ve , case cohort study in 12 819 apparently healthy middle-aged men and women in the Atherosclerosis Risk in Communities study , the relation between Lp-PLA2 , CRP , traditional risk factors , and risk for CHD events over a period of ≈6 years was examined in a proportional hazards model , stratified by LDL-C. Lp-PLA2 and CRP levels were higher in the 608 cases than the 740 noncases . Both Lp-PLA2 and CRP were associated with incident CHD after adjustment for age , sex , and race with a hazard ratio of 1.78 for the highest tertile of Lp-PLA2 and 2.53 for the highest category of CRP versus the lowest categories . Lp-PLA2 correlated positively with LDL-C ( r = 0.36 ) and negatively with HDL-C ( r = −0.33 ) but not with CRP ( r = −0.05 ) . In a model adjusted for traditional risk factors including LDL-C , the association of Lp-PLA2 with CHD was attenuated and not statistically significant . For individuals with LDL-C below the median ( 130 mg/dL ) , Lp-PLA2 and CRP were both significantly and independently associated with CHD in fully adjusted models . For individuals with LDL-C < 130 mg/dL , those with both Lp-PLA2 and CRP levels in the highest tertile were at the greatest risk for a CHD event . Conclusions —Lp-PLA2 and CRP may be complementary in identifying individuals at high CHD risk who have low Lipoprotein ( a ) may be an important risk factor for atherosclerosis . It is widely accepted that lipoprotein ( a ) levels are raised in patients with coronary heart disease , but there is some doubt about the causality of the relationship . In addition , little is known about the relationship between lipoprotein ( a ) and either stroke or peripheral arterial disease , nor about the role of lipoprotein ( a ) in women . Subjects aged 55 - 74 years ( n=1592 ) were selected at r and om from 11 general practice s in Edinburgh , Scotl and and followed up for 5 years . The incidences of myocardial infa rct ion , intermittent claudication and stroke were 13.4 , 9.4 and 3.7 % , respectively . Raised lipoprotein ( a ) levels at baseline were associated with an increased risk ( 95 % confidence interval ) of myocardial infa rct ion RR 1.15 ( 1.00 , 1.32 ) , intermittent claudication RR 1.32 ( 1.10 , 1.57 ) but not significantly for stroke RR 1.24 ( 0.93 , 1.64 ) . This increased risk persisted for intermittent claudication after adjustment for baseline cardiovascular disease and other risk factors RR 1.20 ( 1.00 , 1.43 ) , but for myocardial infa rct ion became non-significant RR 1.06 ( 0.91 , 1.23 ) . The risk of disease associated with raised lipoprotein ( a ) was slightly higher in women than in men , especially for intermittent claudication ( men RR 1.09 ( 0.87 , 1.36 ) compared to women RR 1.37 ( 1.01 , 1.87 ) ) . In conclusion , we found that lipoprotein ( a ) was an independent predictor of cardiovascular events in both sexes . The association between lipoprotein ( a ) and cardiovascular events may have been stronger in women than in men , and for peripheral arterial disease than myocardial infa rct ion and stroke Background and Purpose — There is scant population -based evidence regarding extracranial carotid plaque surface irregularity and ischemic stroke . Using a prospect i ve cohort design , we evaluated the association of carotid plaque surface irregularity and the risk of ischemic stroke in a multiethnic population . Methods — High-resolution B-mode ultrasound of the carotid arteries was performed in 1939 stroke-free subjects ( mean age 69±10.0 years ; 59 % women ; 53 % Hispanic , 25 % black , 22 % white ) . Plaque was defined as a focal protrusion 50 % greater than the surrounding area and localized along the extracranial carotid tree ( internal carotid artery/bifurcation vs common carotid artery ) . Plaque surface was categorized as regular or irregular . Cox proportional hazard models were used to assess the association of surface characteristics and the risk of ischemic stroke . Results — Among 1939 total subjects , carotid plaque was visualized in 56.3 % ( 1 plaque : 21.6 % , > 1 plaque : 34.7 % , irregular plaque : 5.5 % ) . During a mean follow up of 6.2 years after ultrasound examination , 69 ischemic strokes occurred . Unadjusted cumulative 5-year risks of ischemic stroke were : 1.3 % , 3.0 % , and 8.5 % for no plaque , regular plaque , and irregular plaque , respectively . After adjusting for demographics , traditional vascular risk factors , degree of stenosis , and plaque thickness , presence of irregular plaque ( vs no plaque ) was independently associated with ischemic stroke ( Hazard ratio , 3.1 ; 95 % CI , 1.1 to 8.5 ) . Conclusions — The presence of irregular carotid plaque independently predicted ischemic stroke in a multiethnic cohort . Plaque surface irregularities assessed by B-mode ultrasonography may help identify intermediate- to high-risk individuals beyond their vascular risk assessed by the presence of traditional risk factors Background and Purpose — Carotid intima-media thickness ( IMT ) is an independent predictor of vascular events in age groups > 45 years . However , there is little information about the predictive value of IMT in younger individuals . Methods — In the Carotid Atherosclerosis Progression Study ( CAPS ; n=5056 ; age range 19 to 90 years ; mean age 50.1 years ) , common carotid artery ( CCA ) IMT , bifurcation IMT , internal carotid artery IMT and vascular risk factors were evaluated at baseline . The incidence of stroke , myocardial infa rct ion ( MI ) , and death was determined prospect ively . Data for younger ( < 50 years ; n=2436 ) and older subjects ( ≥50 years ; n=2620 ) were analyzed separately using Cox proportional hazard regression models . Results — During a mean follow-up period of 4.2 years , there were 228 cases of MI , 107 strokes , and 50 deaths . IMT at all carotid segments was highly predictive of all end points ( eg , hazard rate ratios [ HRRs ] per 1 SD CCA-IMT increase were 1.43 [ 95 % CI : 1.35 to 1.51 ] for MI , 1.47 [ 1.35 to 1.60 ] for stroke , and 1.45 [ 1.38 to 1.52 ] for MI , stroke or death ; all P<0.0001 ) . Even after adjustment for age , sex , and vascular risk factors , the predictive value of CCA-IMT and bifurcation IMT remained significant for MI and the combined end point . For the latter , the HRRs were considerably higher in the younger than in the older age group ( eg , HRR per 0.1 mm CCA-IMT was 1.34 [ 1.16 to 1.55 ] vis-à-vis 1.10 [ 1.05 to 1.15 ] ; P=0.011 for age-IMT interaction ) . Conclusions — Carotid IMT independently predicts future vascular events . Its predictive value is at least as high in younger subjects as in older subjects OBJECTIVE To assess prospect ively the risk of myocardial infa rct ion ( MI ) associated with elevated levels of lipoprotein(a ) ( Lp[a ] ) . DESIGN Nested case-control study using prospect ively collected plasma sample s. SETTING Participants in the Physicians ' Health Study . PARTICIPANTS A total of 14,916 male physicians aged 40 to 84 years with no prior history of MI or stroke provided plasma sample s at baseline and were followed up prospect ively for an average period of 60.2 months . Sample s from 296 physicians who subsequently developed MI were analyzed for Lp(a ) level together with paired controls , matched for smoking status and age . MAIN OUTCOME MEASURE Fatal or nonfatal acute MI . RESULTS The distribution of Lp(a ) level among cases was virtually identical to that of controls ( P = .88 ) , and there was no significant difference between groups for median Lp(a ) levels ( 103.0 mg/L vs 102.5 mg/L ; P = .73 ) . In analyses controlling for age and smoking status , we found no evidence of association between increasing level of Lp(a ) and risk of MI ( relative risks from lowest to highest quintiles of Lp(a ) : 1.00 , 0.97 , 0.83 , 0.88 , and 1.07 ; P for trend = .93 ) or a threshold effect at any prespecified cutoff of Lp(a ) level ( relative risks associated with Lp[a ] levels above the 25th , 50th , 75th , 90th , and 95th percentiles of the control distribution , respectively : 1.04 , 1.00 , 1.19 , 1.00 , and 1.07 ; all P values nonsignificant ) . Further adjustment for both lipid and nonlipid cardiovascular risk factors had no material impact . CONCLUSIONS In this prospect i ve study of predominantly middle-aged white men , we found no evidence of association between Lp(a ) level and risk of future MI . These data do not support the use of Lp(a ) level as a screening tool to define cardiovascular risk among this population BACKGROUND Elevated lipoprotein(a ) [ Lp(a ) ] levels have been associated with the presence of atherosclerotic disease . However , the results of prospect i ve studies of Lp(a ) and cardiovascular disease have been contradictory . METHODS AND RESULTS From 1968 through 1982 , lipoprotein analysis was performed in 11,335 Olmsted County residents . Quantitative cholesterol and triglycerides were obtained along with semiquantitative Lp(a ) levels based on electrophoretic pattern . Lp(a ) b and s were scored from 0 ( absent ) to 3 ( increased ) . A cohort of 4967 men and 4968 women with no prior history of atherosclerotic disease who had baseline Lp(a ) determinations were followed up for 14 years for development of coronary artery disease ( CAD ) and cerebrovascular disease ( CVD ) . During 131,330 person-years of follow-up , there were 1848 CAD events and 841 CVD events . Age , diabetes , hypertension , cholesterol , and triglycerides were significantly and independently associated with an increased risk of CAD and CVD in men and women . There was a significant increase in the adjusted hazards ratio for CAD with increasing Lp(a ) levels for men and women . For Lp(a ) level 3 , the hazard ratio was 1.9 ( range , 1.3 to 2.9 ) in women and 1.6 ( range , 1.0 to 2.5 ) in men . The adjusted hazard ratio for CVD showed an irregular association with Lp(a ) levels in men and no association in women . CONCLUSIONS In this cohort of 9936 men and women initially free of cardiovascular disease who were followed up for 14 years , Lp(a ) was a significant predictor of risk of future CAD . Lp(a ) was a weak risk factor for CVD in men and was not a significant predictor of CVD risk in women Context Inflammatory markers , such as C-reactive protein ( CRP ) , independently predict future coronary artery disease in patients without known disease at baseline . However , an elevated CRP level also predicts all-cause mortality ; therefore , it may not be specific for cardiovascular disease . Contribution This prospect i ve casecontrol study showed that CRP level predicted the development of acute cardiovascular events but not cancer among 28 345 women followed for a mean of 58 months . Clinical Implication s parental history of coronary heart disease . In women , CRP level appears specifically predictive of car-diovascular disease but not cancer . This study adds further evidence that CRP levels may be useful in the clinical prediction of cardiovascular risk , at least in population s. The Editors Recent evidence suggests that atherosclerosis is in part a chronic low- grade inflammatory condition ( 1 ) , and prospect i ve epidemiologic studies have demonstrated that plasma markers of inflammation , such as C-reactive protein ( CRP ) , are strong independent predictors of future coronary events in apparently healthy persons ( 2 - 6 ) . However , as an acute-phase reactant , CRP increases dramatically in various pathologic conditions . Moreover , CRP has been shown to predict all-cause mortality ( 7 , 8) , an observation that raises the possibility that CRP may not be specific for vascular disease . To evaluate this hypothesis , we directly compared the predictive value of CRP for incident cancer and cardiovascular disease , the two most important determinants of all-cause mortality in the western world . Methods We performed a prospect i ve , nested casecontrol analysis within the Women 's Health Study , an ongoing r and omized , double-blind , placebo-controlled trial of aspirin and vitamin E for primary prevention of heart disease and cancer , which involves 39 876 U.S. women 45 years of age and older . Of these study participants , 28 345 ( 71 % ) provided baseline blood sample s , which were stored at 70 C until the time of laboratory analysis . In the Women 's Health Study , all participants are followed prospect ively for incident health events , including cancer and cardiovascular events . The methods used for cohort follow-up , end-point ascertainment , and adjudication for both cancer and cardiovascular events are described in detail elsewhere ( 5 , 9 ) . For this study , we defined case- patients as apparently healthy women who provided an adequate baseline plasma sample and who subsequently developed cancer ( n = 513 ) or an acute cardiovascular event ( myocardial infa rct ion , stroke , or cardiovascular death ) ( n = 130 ) over a mean follow-up period of 58 months . For each woman who had confirmed cancer or cardiovascular event during follow-up , one control of the same age ( 1 year ) and smoking habit ( former smoker , current smoker , or nonsmoker ) was selected from among participants who provided baseline plasma sample s and remained free of reported disease during the same follow-up period . Using these criteria , we evaluated 643 case- patients and an equal number of controls in two separate matched pairs , one for cancer ( n = 513 ) and another for cardiovascular events ( n = 130 ) . The Institutional Review Board of the Brigham and Women 's Hospital approved this study . For each case-patient and control , plasma stored since the baseline examination was thawed and assayed for CRP levels by using a high-sensitivity assay ( Dade Behring , Newark , Delaware ) ( 10 ) . Blood specimens were analyzed in blinded pairs with the position of the patient 's specimen varied at r and om to reduce the possibility of systematic bias and to decrease interassay variability . The day-to-day precision values , at CRP concentrations of 0.15 mg/L and 0.49 mg/L , were 4.9 % and 6.4 % , respectively . Because CRP values are skewed rightward , median plasma concentrations were computed , and the significance of any difference in the distributions between the case- patients and controls was assessed by performing the Wilcoxon rank-sum test . We then used conditional logistic regression models to determine the risk for developing cancer or cardiovascular end points after dividing the study sample into quartiles on the basis of the distribution of the control group . Adjusted estimates of risk were obtained by use of similar models that accounted for the matching variables and that controlled for r and omized treatment assignment ( for vitamin E , aspirin , or both ) , body mass index , diabetes mellitus , history of hyperlipidemia , history of hypertension , and parental history of coronary heart disease . All analyses were performed by using SAS software , release 8.2 ( SAS Institute , Inc. , Cary , North Carolina ) . All P values were two tailed , and CIs were computed at the 95 % level . The funding sources played no role in the design , conduct , or reporting of the study . Results Table 1 shows the baseline characteristics of the study participants . We noted no significant differences at baseline between women who subsequently developed cancer and those who did not . As expected , women who subsequently developed cardiovascular events had an increased baseline prevalence of hyperlipidemia , hypertension , diabetes , and obesity compared with controls who did not develop vascular events during follow-up . Table 1 . Baseline Clinical Characteristics of the Study Participants Overall , median levels of CRP at baseline among women who subsequently developed cancer ( 2.6 mg/L [ interquartile range , 1.1 to 5.9 mg/L ] ) were not significantly different from those of the control group ( 2.5 mg/L [ interquartile range , 0.9 to 5.5 mg/L ] ) ( P > 0.2 ) . Furthermore , we observed no evidence of an association between baseline CRP level and the development of cancer in site-specific analyses evaluating carcinoma of the breast ( n = 223 ) , ovary or uterus ( n = 75 ) , colon ( n = 44 ) , lung ( n = 32 ) , hematopoietic system ( n = 31 ) , thyroid ( n = 14 ) , bladder ( n = 9 ) , brain ( n = 8) , or pancreas ( n = 8) ; melanoma ( n = 31 ) ; or other types of cancer ( n = 38 ) . In contrast , and consistent with previous work in this cohort for the end point of any vascular event ( 5 ) , median CRP levels at baseline among women who subsequently developed cardiovascular disease ( 5.1 mg/L [ interquartile range , 2.6 to 8.5 mg/L ] ) were significantly higher than those of the control group ( P < 0.001 ) . Table 2 presents relative risks for developing either cancer or cardiovascular disease according to increasing quartiles of CRP levels obtained at study entry . As Table 2 shows , there was little evidence that baseline levels of CRP predicted incident cancer in either crude or adjusted analyses . We found similar results after additional correction for alcohol use and age at menarche ( data not shown ) . In contrast , increasing quartiles of baseline CRP level were a strong marker of risk for incident cardiovascular disease in crude and adjusted analyses . For example , the adjusted relative risks from the lowest to the highest quartiles of baseline CRP levels were 1.0 , 2.9 , 3.4 , and 5.6 , respectively ( P for trend < 0.001 ) . Table 2 . Relative Risk for Future Cancer and Cardiovascular Events , according to Baseline Plasma C-Reactive Protein Level Discussion In this prospect i ve study of apparently healthy middle-aged and older women , baseline plasma CRP concentrations were not significantly related to the incidence of future cancer but were a strong independent predictor of future myocardial infa rct ion , stroke , and cardiovascular death . We believe these data have importance for general medical practice for several reasons . First , our data corroborate the findings in several previous reports ( 2 - 6 ) that baseline levels of CRP predict future vascular events among apparently healthy men and women ( 2 - 6 ) and that CRP level adds to the predictive value of total and high-density lipoprotein cholesterol levels ( 5 , 11 ) . As a result of these earlier findings , outpatient screening for CRP has recently become available . However , if CRP is clinical ly nonspecific , as two recent studies evaluating all-cause mortality suggest ( 7 , 8) , then screening for this inflammatory marker might have reduced diagnostic utility . Thus , our finding that CRP appears to be specific for incident vascular disease but not for incident cancer has substantial clinical importance and suggests that data linking CRP level to overall death rates may have been due to the large contribution that vascular disorders make to all-cause mortality , particularly in the western world . Second , the relative risks for future myocardial infa rct ion or stroke observed among women in the top versus bottom quartile of baseline CRP in this analysis are somewhat greater than those previously reported from this cohort for the end point of any vascular eventan end point that included not only myocardial infa rct ion , stroke , and cardiovascular disease mortality , but also coronary revascularization ( 5 ) . Thus , these data also suggest that CRP level may be a stronger marker for events involving atherosclerotic plaque rupture and acute thrombosis than for events primarily involving progression of lesional stenosis . These epidemiologic data are thus consistent with the hypothesis that inflammation is an important determinant of plaque vulnerability ( 12 ) . Finally , we believe that our observation that CRP levels do not strongly predict future cancers is itself of pathophysiologic interest ; this is of particular interest because levels of CRP and other inflammatory biomarkers are known to increase after development of certain malignancies ( 13 , 14 ) . As such , our data also suggest that the systemic inflammatory component of cancer previously reported in cross-sectional studies may be a late development in the genesis of that disease but is not likely to prove useful in determining risk among healthy persons . Several limitations of our study deserve attention . Plasma CRP levels increase acutely in a wide variety of pathologic conditions , including febrile illness , various inflammatory states , and trauma ( 15 ) . In BACKGROUND While it has been suggested that periodontal disease may be associated with coronary heart disease , or CHD , there are no data to suggest that the elimination of chronic dental infections actually lowers the risk of developing chronic CHD . The goal of this study was to determine whether people with a definitive elimination of all potential dental infections -- edentulous people , who are at the optimum endpoint of dental infection elimination from a CHD perspective -- lower their CHD risk over time when compared with people who have a specific dental infection , periodontitis . METHODS The authors examined data from a prospect i ve cohort of 4,027 people who participated in the First National Health and Nutrition Examination Survey , or NHANES I , Epidemiologic Follow-up Study . The primary outcome measure was the first CHD event . RESULTS During a mean follow-up of 17 years , there were 1,238 CHD events ( 538 fatal ) . The confirmed elimination of chronic dental infections did not lead to a decreased risk of experiencing a CHD event ( relative risk , 1.02 ; 95 percent confidence interval , 0.86 - 1.21 ) . The CHD risk among people with and without chronic dental infections remained constant over time with respect to each other ( test for increasing or decreasing trend over time : not significant , chi2(1 ) = 0.48 ; P = .93 ) . CONCLUSIONS People who had a complete , definitive and long-term elimination of all potential dental infections through extraction of all teeth did not have lower CHD risk when compared with people with diagnosed periodontitis . CLINICAL IMPLICATION S Until evidence is found to the contrary , the authors suggest that prevention of CHD should not be used as the basis for recommending treatment to eliminate chronic dental infections The role of hemostatic factors as predictors of coronary heart disease ( CHD ) and total mortality is poorly understood . Therefore , we carried out a prospect i ve cohort study in Finl and . In 1992 , a r and om population sample of 2378 men and women aged 45 to 64 years was investigated and then followed up until December 31 , 1998 . During the follow-up , 133 CHD events were observed ; 73 were among participants free of CHD at baseline . The total number of deaths was 124 . After adjustment for traditional risk factors and prevalent CHD at baseline and correction for regression dilution bias , a 1-SD increase in plasminogen was associated with a 1.41-fold ( 95 % CI 1.09 to 1.81 ) increase in CHD risk . The predictive power of plasminogen depended significantly on the level of total cholesterol being stronger for persons with high cholesterol . A 1-SD increase in fibrinogen was associated with a 1.23-fold ( 95 % CI 1.05 to 1.44 ) increase in all-cause mortality , but its association with CHD events did not reach statistical significance . Factor VII antigen or coagulant activity or lipoprotein(a ) were not independent predictors of CHD risk . These findings support the role of plasminogen as a risk factor for CHD events BACKGROUND Determination of C-reactive protein ( CRP ) level has been suggested to improve cardiovascular disease ( CVD ) risk assessment . This study examines the utility of CRP levels to assess CVD risk in a community setting . METHODS We performed a prospect i ve observational cohort study on a community population sample . A total of 1949 men and 2497 women without CVD from the Framingham Heart Study underwent CVD risk factor assessment . Initial CVD events during 8 years of follow-up were recorded . RESULTS There were 283 major CVD and 160 major coronary heart disease incident events . Age- , sex- , and multivariable-adjusted analyses generally used CRP level categories of less than 1 , 1 to 3 , and greater than 3 mg/L. In age- and sex-adjusted models , the traditional risk factors and elevated CRP levels indicated increased risk . The age- and sex-adjusted relative risk ( RR ) and 95 % confidence interval ( CI ) of CRP level greater than 3 mg/L for major CVD was elevated ( RR , 1.60 ; 95 % CI , 1.19 - 2.14 ) , with evidence of attenuation ( RR , 1.22 ; 95 % CI , 0.90 - 1.66 ) in multivariable models . The C statistic , a measure of the discriminatory capability of the prediction models , was 0.74 for prediction of major CVD with age and CRP level . In multivariable models that included traditional risk factors , the C statistic was 0.78 , a value that was unchanged with the addition of CRP to the multivariable model . Similar relations were noted for major coronary heart disease events . CONCLUSION Elevated CRP level provided no further prognostic information beyond traditional office risk factor assessment to predict future major CVD and major coronary heart disease in this population sample Carotid arterial intima-media thickness measured with B-mode ultrasonography is used as a noninvasive end point ( that is , an outcome ) in epidemiologic studies and clinical trials to gauge progression and regression of atherosclerosis [ 1 - 3 ] . As such , carotid arterial intima-media thickness , expressed as a single measurement ( in millimeters ) or a rate of change ( in millimeters per year ) , is used as a surrogate end point for atherosclerosis of the coronary artery . However , its relation to coronary events has not been fully explored . It is well established that progression of atherosclerosis of the coronary artery determined by sequential coronary angiography is predictive of coronary events [ 4 - 6 ] . A close histologic relation between carotid and coronary atherosclerosis has been seen in autopsy studies [ 7 ] , and the two arterial beds share many risk factors that contribute to the progression of atherosclerosis [ 8 , 9 ] . Furthermore , carotid arterial intima-media thickness has been a good indicator of the presence and extent of coronary artery disease in observational studies [ 10 , 11 ] . The Cholesterol Lowering Atherosclerosis Study [ 12 ] was a clinical arterial imaging trial design ed to study the effects of colestipol-niacin therapy on progression of atherosclerosis in the coronary , femoral , and carotid arteries . We have reported that treatment is beneficial for all three arterial beds [ 3 , 13 - 16 ] . In addition , long-term follow-up of the study cohort indicated that progression of coronary artery disease was predictive of coronary events [ 4 ] . The objectives of this long-term follow-up of the Cholesterol Lowering Atherosclerosis Study cohort are 1 ) to determine whether carotid arterial intima-media thickness [ expressed as a single measurement or as a rate of change ] predicts coronary events , 2 ) to compare the relative prognostic utility of the two carotid arterial intima-media thickness measures ; and 3 ) to compare the relative prognostic contribution of the two carotid arterial intima-media thickness measures with an angiographic measure of coronary artery disease progression and lipid levels . Methods Study Design In the Cholesterol Lowering Atherosclerosis Study , 188 nonsmoking men 40 to 59 years of age who had previously had coronary artery bypass graft surgery were r and omly assigned to receive colestipol-niacin therapy plus dietary therapy ( target diet , < 125 mg of cholesterol per day and 22 % of energy as fat , 10 % as polyunsaturated fat , and 4 % as saturated fat ) or placebo plus dietary therapy ( target diet , < 250 mg of cholesterol per day and 26 % of energy as fat , 10 % as polyunsaturated fat , and 5 % as saturated fat ) [ 12 ] . In addition to the primary end point provided by coronary angiograms at baseline and after 2 years of treatment , B-mode ultrasonography of the carotid artery was done at baseline and every 6 months during the 2-year treatment period . The cohort for this study consisted of patients who had completed the 2-year treatment period and had evaluable coronary and carotid arterial end points . Baseline and 2-year coronary artery films were processed by quantitative coronary angiography in t and em ; frames were matched for orientation and degree of contrast filling [ 17 ] . For each evaluable arterial segment , three sequential frames were processed in end diastole . For each coronary lesion , percent diameter stenosis was obtained as the average over the three sequential frames . For each patient , the change in percent diameter stenosis over 2 years was averaged for all evaluable coronary artery lesions . B-mode ultrasonographic images of the carotid artery were obtained with a Diasonics CV400 system with a 7.5-MHz probe ( Diasonics , Milpetas , California ) . Longitudinal views of the far wall of the right distal common carotid artery were recorded with the minimum gain necessary for clear visualization of structures . Common carotid arterial intima-media thickness was measured with an automated computerized edge-detection algorithm [ 18 ] . The distance between the echoes arising from the blood-intima interface and the media-adventitia interface was taken as the measure of intima-media thickness . Distal common carotid arterial intima-media thickness was the average of approximately 80 intima-media thickness measurements made over 1 cm . Measurements were made by persons blinded to treatment assignment and the occurrence of clinical coronary events . Follow-up for Coronary Events After completion of the 2-year treatment period , the occurrence of major medical events and information on all medications ( including lipid-lowering agents ) was determined for all patients by a clinic visit ( 59 % of all follow-ups ) or a mailed question naire ( 41 % ) at annual follow-up points through 30 June 1994 . No ascertainment bias was associated with method of follow-up . Coronary events were nonfatal acute myocardial infa rct ion , coronary death , and need for coronary artery revascularization [ percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery ] because of recurrence or worsening of angina pectoris . For all patient-reported events , hospital records were obtained for confirmation , and all causes of death were confirmed by hospital records and death certificates . Myocardial infa rct ion was diagnosed by a cardiologist who was blinded to treatment assignment and ultrasonographic and angiographic end point measures . Myocardial infa rct ion was confirmed if two of the following three criteria were substantiated : typical chest pain , positive creatine phosphokinase-MB , and a new Q wave on electrocardiogram . In order to include only events that were clearly related to clinical symptoms , we did not count 1 ) coronary artery revascularizations that were related to the reading of the 2-year coronary angiogram or 2 ) silent myocardial infa rct ions noted on electrocardiograms at annual follow-up examinations as clinical coronary events . Statistical Analysis The two dependent variables were time from completion of the trial to nonfatal myocardial infa rct ion or coronary death and time from completion of the trial to the first coronary event ( nonfatal myocardial infa rct ion , coronary death , or coronary artery revascularization ) . The two independent variables were the absolute carotid arterial intima-media thickness ( in millimeters ) , measured at the end of the 2-year trial , and the annual rate of change in carotid arterial intima-media thickness ( in millimeters per year ) , evaluated over the 2-year trial . The intima-media thickness change rate was computed for each patient by fitting a least-squares regression line relating intima-media thickness measurements to time in the study . The average number of ultrasonographic examinations per patient was 2.8 0.4 . The absolute carotid arterial intima-media thickness is a cumulative measure of carotid atherosclerosis , whereas the intima-media thickness change rate represents the speed with which atherosclerosis of the carotid artery is changing . Univariate and multivariate proportional hazards models were used to test for relations ( overall and within each treatment group ) between the intima-media thickness variables and coronary event rates . Covariates included the baseline value for intima-media thickness ( for analyses of intima-media thickness change rates ) and treatment group ( for analyses of the total sample ) . Because patients had the option to continue their r and omized , blinded treatment in a 2-year extension of the Cholesterol Lowering Atherosclerosis Study , an additional covariate indexed whether a given patient was treated in the 2-year extension period . Likelihood ratio tests for trend in coronary event rates used each intima-media thickness variable as continuous data . Hazard ratios ( as estimators of relative risks ) and 95 % CIs were expressed per SD ( 0.03 mm/year for the carotid arterial intima-media thickness change rate and 0.13 mm for the absolute carotid arterial intima-media thickness ) . Absolute carotid arterial intima-media thickness values were categorized by quartiles based on the distribution of the baseline intima-media thickness for all patients ; carotid arterial intima-media thickness change rates were categorized by quartiles based on the distribution of changes in the placebo group . Hazard ratios were then computed for each of the upper quartiles relative to the first . Because earlier analyses of the study cohort showed a significant relation between progression of coronary artery disease ( assessed by the change in percent diameter stenosis using quantitative coronary angiography ) and coronary events [ 4 ] , we also evaluated the relative prognostic contributions of this angiographic measure of coronary artery disease progression and the ultrasonographic measure of carotid arterial intima-media thickness progression . For the change in percent diameter stenosis , hazard ratios and 95 % CIs were expressed per 10 % change in percent diameter stenosis . The cutoff of 10 % change is double the measurement error for percent diameter stenosis on short-term repeated angiography . The joint prognostic contribution of the carotid artery and coronary artery measures of atherosclerosis with lipid levels that were found to be significantly different between patients with and without coronary events was also evaluated . Values given are the mean SD unless otherwise indicated . Role of the Funding Source The authors were responsible for data collection , data management , statistical analyses , and data interpretation . Research was supported by the National Heart , Lung , and Blood Institute through investigator-initiated grants to Dr. Hodis ( RO1-HL-49885 ) and Dr. Mack ( RO3-HL-54532 ) . The funding source had no role in deciding whether the study would be su bmi tted for publication . Results Characteristics of the Cohort at Baseline and after Treatment Of the 188 patients r and omly assigned to treatment , 42 ( 22 % ) were excluded from the study : Eleven did not have a baseline ultrasonogram , 13 had no ultrasonographic Few studies have determined whether greater carotid artery intima-media thickness ( IMT ) in asymptomatic individuals is associated prospect ively with increased risk of coronary heart disease ( CHD ) . In the Atherosclerosis Risk in Communities Study , carotid IMT , an index of generalized atherosclerosis , was defined as the mean of IMT measurements at six sites of the carotid arteries using B-mode ultrasound . The authors assessed its relation to CHD incidence over 4 - 7 years of follow-up ( 1987 - 1993 ) in four US communities ( Forsyth County , North Carolina ; Jackson , Mississippi ; Minneapolis , Minnesota ; and Washington County , Maryl and ) from sample s of 7,289 women and 5,552 men aged 45 - 64 years who were free of clinical CHD at baseline . There were 96 incident events for women and 194 for men . In sex-specific Cox proportional hazards models adjusted only for age , race , and center , the hazard rate ratio comparing extreme mean IMT ( > or = 1 mm ) to not extreme ( < 1 mm ) was 5.07 for women ( 95 % confidence interval 3.08 - 8.36 ) and 1.85 for men ( 95 % confidence interval 1.28 - 2.69 ) . The relation was grade d ( monotonic ) , and models with cubic splines indicated significant nonlinearity . The strength of the association was reduced by including major CHD risk factors , but remained elevated at higher IMT . Up to 1 mm mean IMT , women had lower adjusted annual event rates than did men , but above 1 mm their event rate was closer to that of men . Thus , mean carotid IMT is a noninvasive predictor of future CHD incidence CONTEXT Guidelines advise that all adults undergo coronary heart disease ( CHD ) risk assessment to guide preventive treatment intensity . Although the Framingham Risk Score ( FRS ) is often recommended for this , it has been suggested that risk assessment may be improved by additional tests such as coronary artery calcium scoring ( CACS ) . OBJECTIVES To determine whether CACS assessment combined with FRS in asymptomatic adults provides prognostic information superior to either method alone and whether the combined approach can more accurately guide primary preventive strategies in patients with CHD risk factors . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve observational population -based study , of 1461 asymptomatic adults with coronary risk factors . Participants with at least 1 coronary risk factor ( > 45 years ) underwent computed tomography ( CT ) examination , were screened between 1990 - 1992 , were contacted yearly for up to 8.5 years after CT scan , and were assessed for CHD . This analysis included 1312 participants with CACS results ; excluded were 269 participants with diabetes and 14 participants with either missing data or had a coronary event before CACS was performed . MAIN OUTCOME MEASURE Nonfatal myocardial infa rct ion ( MI ) or CHD death . RESULTS During a median of 7.0 years of follow-up , 84 patients experienced MI or CHD death ; 70 patients died of any cause . There were 291 ( 28 % ) participants with an FRS of more than 20 % and 221 ( 21 % ) with a CACS of more than 300 . Compared with an FRS of less than 10 % , an FRS of more than 20 % predicted the risk of MI or CHD death ( hazard ratio [ HR ] , 14.3 ; 95 % confidence interval [ CI ] ; 2.0 - 104 ; P = .009 ) . Compared with a CACS of zero , a CACS of more than 300 was predictive ( HR , 3.9 ; 95 % CI , 2.1 - 7.3 ; P<.001 ) . Across categories of FRS , CACS was predictive of risk among patients with an FRS higher than 10 % ( P<.001 ) but not with an FRS less than 10 % . CONCLUSION These data support the hypothesis that high CACS can modify predicted risk obtained from FRS alone , especially among patients in the intermediate-risk category in whom clinical decision making is most uncertain BACKGROUND Although hemostatic factors contribute to acute coronary syndromes and atherogenesis , few studies have prospect ively evaluated the association between multiple hemostatic factors and coronary heart disease incidence . METHODS AND RESULTS The Atherosclerosis Risk in Communities Study recruited 14,477 adults from 45 to 64 years of age who were initially free of coronary heart disease . Coronary disease risk factors and several plasma hemostatic factors were measured , and incidence of coronary heart disease was ascertained during an average follow-up of 5.2 years . Age- , race- , and field center-adjusted relative risks of coronary heart disease were significantly elevated ( P < or = .05 ) per higher value of fibrinogen ( relative risk : men , 1.76 ; women , 1.54 ) , white blood cell count ( men , 1.68 ; women , 2.23 ) , factor VIII coagulant activity ( women , 1.25 ) , and von Willebr and factor antigen ( men , 1.20 ; women , 1.18 ) . Adjustment for other risk factors attenuated these associations for fibrinogen ( adjusted relative risk : men , 1.48 ; women , 1.21 ) , and it eliminated the white blood cell count , factor VIII , and von Willebr and factor associations , consistent with the other risk factors either confounding or partly operating through their effects on the hemostatic variables . Adjusted st and ardized relative risks of total mortality , ranging from 1.13 to 1.37 , were also elevated ( P < .05 ) in relation to these four factors . There was no association of coronary disease incidence with factor VII , protein C , antithrombin III , or platelet count . CONCLUSIONS Elevated levels of fibrinogen , white blood cell count , factor VIII , and von Willebr and factor are risk factors and may play causative roles in coronary heart disease . However , their measurement in healthy adults appears to add little to prediction of coronary events beyond that of more established risk factors OBJECTIVE To establish whether elevated lipoprotein(a ) [ Lp(a ) ] , detected as a sinking pre-beta-lipoprotein b and on electrophoresis of fresh plasma , is an independent risk factor for the development of premature coronary heart disease ( CHD ) in men . DESIGN AND SETTING Prospect i ve study of the Framingham offspring cohort . PARTICIPANTS A total of 2191 men aged 20 to 54 years old who were free of cardiovascular disease when they were examined between 1971 and 1975 . MAIN OUTCOME MEASURES Incident CHD ( myocardial infa rct ion , coronary insufficiency , angina pectoris , or sudden cardiac death ) occurring by age 55 years . RESULTS After a median follow-up of 15.4 years , there were 129 CHD events . The relative risk ( RR ) estimates ( with 95 % confidence intervals [ CIs ] ) for premature CHD derived from a proportional hazards model that included age , body mass index , and the dichotomized risk factor covariables elevated plasma Lp(a ) level , total cholesterol level of 6.2 mmol/L ( 240 mg/dL ) or more , high-density lipoprotein ( HDL ) level less than 0.9 mmol/L ( 35 mg/dL ) , smoking , glucose intolerance , and hypertension were as follows : elevated Lp(a ) level , RR , 1.9 ( 95 % CI , 1.2 - 2.9 ) , prevalence , 11.3 % ; total cholesterol level of 6.2 mmol/L or more , RR , 1.8 ( 95 % CI , 1.2 - 2.7 ) , prevalence , 14.3 % ; HDL level of less than 0.9 mmol/L , RR , 1.8 ( 95 % CI , 1.2 - 2.6 ) , prevalence 19.2 % ; smoking , RR 3.6 ( 95 % CI , 2.2 - 5.5 ) , prevalence , 46.7 % ; glucose intolerance , RR , 2.7 ( 95 % CI , 1.4 - 5.3 ) , prevalence , 2.6 % ; hypertension , RR , 1.2 ( 95 % CI , 0.8 - 1.8 ) , prevalence , 26.3 % . CONCLUSIONS Elevated plasma Lp(a ) is an independent risk factor for the development of premature CHD in men , comparable in magnitude and prevalence ( ie , attributable risk ) to a total cholesterol level of 6.2 mmol/L ( 240 mg/dL ) or more , or an HDL level less than 0.9 mmol/L ( 35 mg/dL ) To prospect ively assess the role of lipoprotein(a ) ( Lp(a ) ) as a risk factor for coronary heart disease , the serum Lp(a ) concentration was determined in 130 subjects without coronary events and in 138 patients in whom coronary events ( i.e. fatal and non-fatal myocardial infa rct ion and cardiac death ) occurred during the 5-year Helsinki Heart Study . The participants of this study ( n = 4081 ) were 40 - 55-year-old men who were devoid of coronary heart disease at the beginning of the trial ; half were r and omized to gemfibrozil and the other half to placebo treatment . In patients with coronary events blood pressure and total cholesterol were not significant predictors of the events but their LDL cholesterol was higher than compared to the control group in this cohort ( P less than 0.05 ) . The serum Lp(a ) concentration was determined by immunoassay from sample s obtained 3 months after the beginning of the trial and then stored at -20 degrees C until analysed . Studies on the effect of long term storage at -20 degrees C on serum Lp(a ) levels did not reveal significant changes in Lp(a ) concentration in sera stored for up to 8.5 years . The distribution of Lp(a ) concentrations were similar in the men with coronary events and the controls . Nor did the mean or median levels of Lp(a ) differ significantly between the two groups . Measurements of Lp(a ) levels in fresh sample s using 2 different immunoassays did not reveal any significant difference between the participants who had survived a myocardial infa rct ion or participants without cardiac events . Thus , we conclude that in the Helsinki Heart Study cohort the serum Lp(a ) level was not a predictor of future coronary events BACKGROUND C-reactive protein is an inflammatory marker believed to be of value in the prediction of coronary events . We report data from a large study of C-reactive protein and other circulating inflammatory markers , as well as up date d meta-analyses , to evaluate their relevance to the prediction of coronary heart disease . METHODS Measurements were made in sample s obtained at base line from up to 2459 patients who had a nonfatal myocardial infa rct ion or died of coronary heart disease during the study and from up to 3969 controls without a coronary heart disease event in the Reykjavik prospect i ve study of 18,569 participants . Measurements were made in paired sample s obtained an average of 12 years apart from 379 of these participants in order to quantify within-person fluctuations in inflammatory marker levels . RESULTS The long-term stability of C-reactive protein values ( within-person correlation coefficient , 0.59 ; 95 percent confidence interval , 0.52 to 0.66 ) was similar to that of both blood pressure and total serum cholesterol . After adjustment for base-line values for established risk factors , the odds ratio for coronary heart disease was 1.45 ( 95 percent confidence interval , 1.25 to 1.68 ) in a comparison of participants in the top third of the group with respect to base-line C-reactive protein values with those in the bottom third , and similar overall findings were observed in an up date d meta- analysis involving a total of 7068 patients with coronary heart disease . By comparison , the odds ratios in the Reykjavik Study for coronary heart disease were somewhat weaker for the erythrocyte sedimentation rate ( 1.30 ; 95 percent confidence interval , 1.13 to 1.51 ) and the von Willebr and factor concentration ( 1.11 ; 95 percent confidence interval , 0.97 to 1.27 ) but generally stronger for established risk factors , such as an increased total cholesterol concentration ( 2.35 ; 95 percent confidence interval , 2.03 to 2.74 ) and cigarette smoking ( 1.87 ; 95 percent confidence interval , 1.62 to 2.16 ) . CONCLUSIONS C-reactive protein is a relatively moderate predictor of coronary heart disease . Recommendations regarding its use in predicting the likelihood of coronary heart disease may need to be review ed A cross sectional and prospect i ve analysis of 3,745 British women aged 60 - 79 years at baseline was undertaken . Among these women there were 570 prevalent cases of coronary heart disease ( CHD ) and 151 new cases among 12,641 person-years of follow up of women who were free of CHD at baseline . Both fibrinogen and CRP were associated with indicators of socioeconomic position in childhood and adulthood and there was a cumulative effect of socioeconomic position from across the life course . The age-adjusted odds ratio ( 95 % confidence interval ) of prevalent CHD for a 1 unit ( 1 g/L ) increase in fibrinogen was 1.29 ( 1.12 , 1.49 ) ; with full adjustment for all potential confounding factors this attenuated to 1.09 ( 0.93 , 1.28 ) . The hazards ratio for incident CHD among those free of disease at baseline was 1.28 ( 1.00 , 1.64 ) ; with full adjustment for all potential confounding factors this attenuated to 1.09 ( 0.84 , 1.44 ) . Similar effects of adjustment for confounding factors were seen for the associations between CRP and both prevalent and incident CHD . By contrast , the strong positive association between smoking ( an established causal risk factor for CHD ) and CHD was not attenuated by adjustment for life course socioeconomic position or other risk factors . We conclude that fibrinogen and CRP predict CHD but may not be causally related to it Because the importance of established risk factors for coronary heart disease ( CHD ) is unclear in older people , the associations of white blood cell ( WBC ) count with the risk for CHD and all-cause mortality were investigated in an elderly cohort that was followed up for 5 years . In 1985 , complete information on the risk factors of interest was available for 884 r and omly selected men , aged 64 to 84 years , from the Dutch town of Zutphen ( participation rate , 74 % ) . Relative risks ( RRs ) for each 10(9)/L increase in WBC count were obtained for the 5-year incidence of and mortality from CHD and all causes . RRs were adjusted for age , body mass index , systolic blood pressure , total and high density lipoprotein cholesterol levels , and cigarette smoking habit . The WBC count was 6.7 + /- 1.8 X 10(9)/L ( means + /- SD ) at baseline . An increased WBC count was independently associated with mortality due to CHD , and the RR amounted to 1.32 ( 95 % confidence interval [ 95 % CI ] , 1.15 to 1.51 ) . For the incidence of CHD the RR was 1.14 ( 95 % CI , 0.98 to 1.32 ) . These associations were observed regardless of cigarette smoking habit . Regarding all-cause mortality , the RR amounted to 1.25 ( 95 % CI , 1.17 to 1.35 ) . This association was especially noticeable among former smokers and those who had never smoked . In conclusion , during 5 years of follow-up WBC count predicted CHD and all-cause mortality in elderly men , independent of the conventional risk factors for CHD BACKGROUND Plasma C-reactive protein ( CRP ) levels recently have been identified as an emerging risk factor for ischemic heart disease ( IHD ) . However , whether plasma CRP levels predict an increased risk for future IHD beyond traditional risk factors has yet to be evaluated in a large prospect i ve , population -based study . METHODS The association between elevated plasma CRP levels and the risk for future IHD was investigated in the prospect i ve , population -based cohort of 2037 IHD-free middle-aged men from the Quebec Cardiovascular Study . During a 5-year follow-up , 105 first IHD events were recorded . Baseline plasma CRP levels were measured using a highly sensitive assay . RESULTS High plasma CRP concentrations ( equal to or above vs below the median level of 1.77 mg/L ) were associated with a significant 1.8-fold increase in IHD risk ( 95 % confidence interval [ CI ] , 1.2 - 2.7 ) . This association remained significant after adjustment for lipid risk factors but not when the simultaneous contribution of nonlipid traditional risk factors was taken into account . Multivariate analyses indicated that CRP level predicted short-term risk for IHD ( events that occurred < or = 2 years after the baseline evaluation ) , but not long-term risk ( > 2 years ) . Moreover , high plasma CRP levels predicted an increased risk for IHD , independent of any other confounder , in younger ( < or = 55 years ) but not in older ( > 55 years ) individuals . CONCLUSION Plasma CRP levels may provide independent information on IHD risk only in younger middle-aged men and in the case of IHD events that may occur relatively soon after the baseline evaluation BACKGROUND Prediction of hard cardiac events ( myocardial infa rct ion and coronary death ) remains difficult in spite of the identification of several relevant risk factors for the development of coronary artery disease ( CAD ) . New indicators of risk might add to our predictive ability . We used measures of coronary artery calcification ( CAC ) found by electron beam tomography ( EBT ) imaging to develop prediction models for hard cardiac events alone and in association with traditional risk factors for CAD . METHODS Two groups of patients were studied : group A , 676 asymptomatic patients ( mean age 52 years , 51 % men ) prospect ively followed up for 32 + /- 7 months after being referred by primary care physicians for a screening EBT , and group B , 10,122 asymptomatic patients screened by EBT at one center and used as controls for calculation of calcium score nomograms . RESULTS The occurrence of hard events in group A patients was related to traditional risk factors for CAD , presence of CAC ( score > 0 ) , Ln ( 1 + absolute calcium score [ CS ] ) , and age- and sex-specific CS percentiles ( CS% ) . Univariate analyses showed that age , smoking , diabetes mellitus , presence of CAC , Ln ( 1 + absolute CS ) , and CS% were predictive of hard events ( all P < .05 ) . Multiple logistic regression analyses demonstrated that CS% was the only significant predictor of events and provided incremental prognostic value when added to traditional risk factors for CAD ( chi-square , P < .001 ) . In a comparison of receiver-operator characteristic curves for prediction of hard events , the area under the curve for CS% plus conventional risk factors and age was significantly larger than that obtained by use of traditional risk factors and age separately as predictors ( 0.84 vs 0.71 , respectively , P < .001 ) . Furthermore , the area under the curve of CS% alone was significantly larger than that of traditional risk factors and age combined ( 0.82 vs 0.71 , P = .028 ) . CONCLUSIONS Patients are usually selected for EBT screening on the basis of the presence of conventional risk factors for CAD . However , an age- and sex-specific calcium score provides the best predictive model for the occurrence of hard coronary events and adds incremental prognostic information to conventional risk factors for CAD OBJECTIVES We sought to determine whether lipid-lowering therapy and antioxidants retard the progression of coronary calcification and prevent atherosclerotic cardiovascular disease ( ASCVD ) events . BACKGROUND The electron beam computed tomography-derived coronary calcium score predicts coronary disease events . Small , uncontrolled studies suggest that vigorous lipid-lowering therapy slows progression of coronary calcification and prevents coronary artery disease events , but controlled , scientific demonstration of these effects is lacking . METHODS We conducted a double-blind , placebo-controlled r and omized clinical trial of atorvastatin 20 mg daily , vitamin C 1 g daily , and vitamin E ( alpha-tocopherol ) 1,000 U daily , versus matching placebos in 1,005 asymptomatic , apparently healthy men and women age 50 to 70 years with coronary calcium scores at or above the 80th percentile for age and gender . All study participants also received aspirin 81 mg daily . Mean duration of treatment was 4.3 years . RESULTS Treatment reduced total cholesterol by 26.5 % to 30.4 % ( p < 0.0001 ) , low-density lipoprotein cholesterol by 39.1 % to 43.4 % ( p < 0.0001 ) , and triglycerides by 11.2 % to 17.0 % ( p < or = 0.02 ) but had no effect ( p = 0.80 ) on progression of coronary calcium score ( Agatston method ) . Treatment also failed to significantly reduce the primary end point , a composite of all ASCVD events ( 6.9 % vs. 9.9 % , p = 0.08 ) . Event rates were related to baseline calcium score ( pre-specified analysis ) and may have been reduced in a subgroup of participants with baseline calcium score > 400 ( 8.7 % vs. 15.0 % , p = 0.046 [ not a pre-specified analysis ] ) . CONCLUSIONS Treatment with alpha-tocopherol , vitamin C , and low doses of atorvastatin ( 20 mg once daily ) did not affect the progression of coronary calcification . Treatment may have reduced ASCVD events , especially in subjects with calcium scores > 400 , but these effects did not achieve conventional levels of statistical significance A large body of evidence suggests that diabetes increases the risk of coronary heart disease ( CHD ) , but whether fasting hyperglycemia is associated with a major risk for CHD is still under debate . The aim of the present study was to investigate the role played by fasting hyperglycemia in the development of cardiovascular disease ( CVD ) in an elderly population when associated with common risk factors for CVD ( i.e. , hypertension , hypercholesterolemia , smoking , etc ) . We analyzed a sample of 455 subjects aged ± 60 years . The risk factors taken into account were systolic and diastolic blood pressure levels , use of antihypertensive drugs , total serum cholesterol , serum triglycerides , and smoking habit . Glycemia was measured at entry on a fasting sample . During the follow‐up period ( mean 6 years ) , the occurrence of CVD was monitored ( criteria for the occurrence of CVD included total cardiovascular mortality , fatal or nonfatal myocardial infa rct ion , symptomatic coronary heart disease [ stable and unstable angina ] , the need for percutaneous transluminal coronary angioplasty or coronary artery bypass graft , fatal or nonfatal stroke , and transient ischemic attack ) . A total of 427 subjects completed the follow‐up . During this period , 73 subjects ( 17.10 % ) developed CVD according to the above criteria . A Cox proportional hazard model was design ed to evaluate the contribution of variables in predicting CVD . Relative risks and 95 % confidence intervals for CVD were calculated from the regression coefficients to study the association between the risk of developing CVD and predicting variables . We found a relation between occurrence of CVD and fasting hyperglycemia : subjects with fasting glycemia , > 126 mg/dl at enrollment , but without previous clinical diagnosis of diabetes , showed a 2.01 times higher risk than those with fasting glycemia < 126 mg/dl . Hence , r and om fasting hyperglycemia can predict the occurrence of CVD in elderly subjects Background : Intensive statin therapy has been shown to improve prognosis in patients with coronary heart disease ( CHD ) . It is unknown whether such benefit is mediated through the reduction of atherosclerotic plaque burden . Aim : To examine the efficacy of high-dose atorvastatin in the reduction of carotid intimal – medial thickness ( IMT ) and inflammatory markers in patients with CHD . Design : R and omised trial . Setting : Single centre . Patients : 112 patients with angiographic evidence of CHD . Interventions : A high dose ( 80 mg daily ) or low dose ( 10 mg daily ) of atorvastatin was given for 26 weeks . Main outcome measures : Carotid IMT , C-reactive protein ( CRP ) and proinflammatory cytokine levels were assessed before and after therapy . Results : The carotid IMT was reduced significantly in the high-dose group ( left : mean ( SD ) , 1.24 ( 0.48 ) vs 1.15 ( 0.35 ) mm , p = 0.02 ; right : 1.12 ( 0.41 ) vs 1.01 ( 0.26 ) mm , p = 0.01 ) , but was unchanged in the low-dose group ( left : 1.25 ( 0.55 ) vs 1.20 ( 0.51 ) mm , p = NS ; right : 1.18 ( 0.54 ) vs 1.15 ( 0.41 ) mm , p = NS ) . The CRP levels were reduced only in the high-dose group ( from 3.92 ( 6.59 ) to 1.35 ( 1.83 ) mg/l , p = 0.01 ) , but not in the low-dose group ( from 2.25 ( 1.84 ) to 3.36 ( 6.15 ) mg/l , p = NS ) . A modest correlation was observed between the changes in carotid IMT and CRP ( r = 0.21 , p = 0.03 ) . Conclusions : In patients with CHD , intensive atorvastatin therapy results in regression of carotid atherosclerotic disease , which is associated with reduction in CRP levels . On the other h and , a low-dose regimen only prevents progression of the disease The association of an elevated level of lipoprotein ( a ) ( Lp(a ) ) with the development of coronary heart disease ( CHD ) remains controversial . Lp(a ) was investigated as a CHD risk factor in the PRIME Study , a prospect i ve cohort study which included 9133 French and Northern Irish men aged 50 - 59 at entry , without a history of CHD and not on hypolipidaemic drugs . During a follow-up of 5 years , 288 subjects experienced at least one CHD event ( myocardial infa rct ion ( MI ) , coronary death , angina pectoris ) . Lp(a ) was measured by immunoassay in all subjects on fresh plasma obtained at entry . Traditional cardiovascular risk factors such as low-density lipoproteins (LDL)-cholesterol , HDL-cholesterol , triglycerides , the presence of diabetes , hypertension or smoking were determined . Logistic regression analysis was used to evaluate Lp(a ) level as a CHD risk factor after controlling for the other risk factors . In addition , its possible interaction with LDL- and HDL-cholesterol levels was investigated . Lp(a ) appeared a significant risk factor ( P<0.0006 ) in the whole cohort without between- population interaction , even if the association was not statistically significant in the Belfast sample . The relative risk ( RR ) of CHD events in subjects with Lp(a ) levels in the highest quartile was 1.5 times that of subjects in the lowest quartile ( RR : 1.56 ; 95 % confidence intervals ( CIs ) : 1.10 - 2.21 ) . A high Lp(a ) level was a risk for MI , coronary death and angina pectoris . A significant interaction term between Lp(a ) and LDL-cholesterol levels , however , was found . The relative CHD risk associated with a Lp(a ) level > or = 33 mg/dl in comparison with Lp(a ) <33 mg/dl increasing gradually from 0.82 ( 95 % CI : 0.28 - 2.44 ) in men with LDL-cholesterol in the lowest quartile ( < 121 mg/dl ) to 1.58 ( 95 % CI : 1.06 - 2.40 ) in the highest quartile ( > 163 mg/dl ) . In conclusion , Lp(a ) increased the risk for MI and angina pectoris , especially in men with a high LDL-cholesterol level . This study which analyzed Lp(a ) level using a measurement independent of apolipoprotein ( a ) size on fresh plasma , has confirmed utility of Lp(a ) as a predictor of CHD BACKGROUND Inflammation may be important in the pathogenesis of atherothrombosis . We studied whether inflammation increases the risk of a first thrombotic event and whether treatment with aspirin decreases the risk . METHODS We measured plasma C-reactive protein , a marker for systemic inflammation , in 543 apparently healthy men participating in the Physicians ' Health Study in whom myocardial infa rct ion , stroke , or venous thrombosis subsequently developed , and in 543 study participants who did not report vascular disease during a follow-up period exceeding eight years . Subjects were r and omly assigned to receive aspirin or placebo at the beginning of the trial . RESULTS Base-line plasma C-reactive protein concentrations were higher among men who went on to have myocardial infa rct ion ( 1.51 vs. 1.13 mg per liter , P<0.001 ) or ischemic stroke ( 1.38 vs. 1.13 mg per liter , P=0.02 ) , but not venous thrombosis ( 1.26 vs. 1.13 mg per liter , P=0.34 ) , than among men without vascular events . The men in the quartile with the highest levels of C-reactive protein values had three times the risk of myocardial infa rct ion ( relative risk , 2.9 ; P<0.001 ) and two times the risk of ischemic stroke ( relative risk , 1.9 ; P=0.02 ) of the men in the lowest quartile . Risks were stable over long periods , were not modified by smoking , and were independent of other lipid-related and non-lipid-related risk factors . The use of aspirin was associated with significant reductions in the risk of myocardial infa rct ion ( 55.7 percent reduction , P=0.02 ) among men in the highest quartile but with only small , nonsignificant reductions among those in the lowest quartile ( 13.9 percent , P=0.77 ) . CONCLUSIONS The base-line plasma concentration of C-reactive protein predicts the risk of future myocardial infa rct ion and stroke . Moreover , the reduction associated with the use of aspirin in the risk of a first myocardial infa rct ion appears to be directly related to the level of C-reactive protein , raising the possibility that antiinflammatory agents may have clinical benefits in preventing cardiovascular disease BACKGROUND Reliable risk stratification is crucial for efficient prevention of coronary artery disease . The following prospect i ve study determined the predictive value of coronary calcifications for future cardiovascular events . METHODS We included 1726 asymptomatic individuals ( 1018 men , 708 women , age 57.7 + /- 13.3 years ) referred for a cardiological examination . Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomography scanner . For quantification of coronary calcifications , we calculated the Agatston score . Over a mean observation period of 40.3 + /- 7.3 months we registered the event rate for cardiac death ( CD ) and myocardial infa rct ion ( MI ) . RESULTS The Agatston score in patients who died of CD ( n = 65 ) or had an MI ( n = 114 ) was significantly higher compared with those without cardiac events ( 458 + /- 228 vs 206 + /- 201 , P < .01 ) . An Agatston score above the 75th percentile was associated with a significantly higher annualized event rate for MI ( 3.6 % vs 1.6 % , P < .05 ) and for CD ( 2.2 % vs 0.9 % ) compared with patients with scores below the 75th percentile . No cardiac events were observed in patients where coronary calcifications could be excluded . CONCLUSIONS By determination of coronary calcifications , patients at risk for future MI and CD could be identified within an asymptomatic population independent of concomitant risk factors . At the same time , future cardiovascular events could be excluded in patients without coronary calcifications PURPOSE Whether serum lipoprotein ( a ) [ Lp(a ) ] levels are an independent risk factor for coronary heart disease has been controversial . We have investigated its status in a prospect i ve population survey , the Second Northwick Park Heart Study . METHODS We recruited 2,616 men 50 to 61 years old from nine primary care practice s in the United Kingdom . Baseline serum Lp(a ) levels were measured by enzyme-linked immunosorbent assay ( ELISA ) and were analyzed in 3 groups ( < 25th percentile , 25th to 75th percentile , and > 75th percentile ) to overcome the problem of some measurements falling below the threshold of the assay . Coronary end points included sudden cardiac death , acute myocardial infa rct ion , silent myocardial infa rct ion on the electrocardiogram , and coronary artery bypass surgery . RESULTS During a mean of 6 years of follow-up , 121 men had coronary events . In a multivariate analysis that also adjusted for fibrinogen , Apo-A1 , Apo-B , and triglyceride levels , we identified several independent risk factors for coronary events , including cholesterol level ( hazard ratio [ HR ] = 1.5 per SD 95 % confidence interval [ CI ] 1.3 to 1.8 ) , diabetes ( HR = 4.1 , 95 % CI : 2 . 0 to 8.4 ) , current versus never smoking ( HR = 2.5 , 95 % CI : 1.5 to 4.1 ) , diastolic blood pressure ( HR = 1.4 per SD , 95 % CI : 1.1 to 1.7 ) , Apo-A1 ( HR = 0.8 per SD , 95 % CI : 0.6 to 0.9 ) , age ( HR = 1.3 per SD , 95 % CI : 1.1 to 1.6 ) , and Lp(a ) ( > 26.3 mg/dL [ 75th percentile ] versus < 2.9 mg/dL [ 25th percentile ] , HR = 1.9 , 95 % CI : 1.1 to 3.3 ] . There was a statistically significant ( P = 0.01 ) difference in risk between the three levels of Lp(a ) . CONCLUSIONS We found that a high Lp(a ) level was an independent predictor of the development of coronary heart disease in middle-aged men Risk prediction functions for incident coronary heart disease ( CHD ) were estimated using data from the Atherosclerosis Risk in Communities ( ARIC ) Study , a prospect i ve study of CHD in 15,792 persons recruited in 1987 - 1989 from four U.S. communities , with follow-up through 1998 . Predictivity of which individuals had incident CHD was assessed by increase in area under ROC curves result ing from adding nontraditional risk factors and markers of sub clinical disease to a basic model containing only traditional risk factors . We also assessed the increase in population attributable risk . The additional factors were body mass index ; waist-hip ratio ; sport activity index ; forced expiratory volume ; plasma fibrinogen , factor VIII , von Willebr and factor , and Lp(a ) ; heart rate ; Keys score ; pack-years smoking ; and sub clinical disease marker carotid intima-media thickness . These factors substantially improved prediction of future CHD for men , less for women , and also increased attributable risks OBJECTIVES This prospect i ve population study was conducted to assess the role of elevated lipoprotein(a ) [ Lp(a ) ] as a coronary risk factor . BACKGROUND The role of elevated Lp(a ) as a risk factor for coronary heart disease is controversial . In addition , little attention has been paid to the interaction of Lp(a ) with other risk factors . METHODS A total of 788 male participants of the Prospect i ve Cardiovascular Münster ( PROCAM ) study aged 35 to 65 years were followed for 10 years . Both Lp(a ) and traditional cardiovascular risk factors ( e.g. , age , low density lipoprotein [ LDL ] cholesterol , high density lipoprotein [ HDL ] cholesterol , triglycerides , systolic blood pressure , cigarette smoking , diabetes mellitus , angina pectoris , and family history of myocardial infa rct ion ) were evaluated in 44 men who suffered from myocardial infa rct ion , and in 744 men who survived without major coronary events or stroke . A multiple logistic function algorithm was used to estimate global cardiovascular risk by the combined effects of traditional risk factors . RESULTS Overall , the risk of a coronary event in men with an Lp(a ) > or = 0.2 g/liter was 2.7 times that of men with lower levels ( 95 % confidence interval [ CI ] : 1.4 to 5.2 ) . This increase in risk was most prominent in men with LDL cholesterol level > or = 4.1 mmol/liter ( relative risk [ RR ] : 2.6 ; 95 % CI : 1.2 to 5.7 ) , with HDL cholesterol < or = 0.9 mmol/liter ( RR 8.3 ; 95 % CI : 2.0 to 35.5 ) , with hypertension ( RR 3.2 ; 95 % CI : 1.4 to 7.2 ) , or within the two highest global risk quintiles ( relative risk : 2.7 ; 95 % CI : 1.3 to 5.7 ) . CONCLUSIONS Lp(a ) increases the coronary risk , especially in men with high LDL cholesterol , low HDL cholesterol , hypertension and /or high global cardiovascular risk OBJECTIVE --To investigate a reported association between dental disease and risk of coronary heart disease . SETTING --National sample of American adults who participated in a health examination survey in the early 1970s . DESIGN -- Prospect i ve cohort study in which participants underwent a st and ard dental examination at baseline and were followed up to 1987 . Proportional hazards analysis was used to estimate relative risks adjusted for several covariates . MAIN OUTCOME MEASURES --Incidence of mortality or admission to hospital because of coronary heart disease ; total mortality . RESULTS --Among all 9760 subjects included in the analysis those with periodontitis had a 25 % increased risk of coronary heart disease relative to those with minimal periodontal disease . Poor oral hygiene , determined by the extent of dental debris and calculus , was also associated with an increased incidence of coronary heart disease . In men younger than 50 years at baseline periodontal disease was a stronger risk factor for coronary heart disease ; men with periodontitis had a relative risk of 1.72 . Both periodontal disease and poor oral hygiene showed stronger associations with total mortality than with coronary heart disease . CONCLUSION --Dental disease is associated with an increased risk of coronary heart disease , particularly in young men . Whether this is a causal association is unclear . Dental health may be a more general indicator of personal hygiene and possibly health care practice OBJECTIVE To examine the relation of white blood cell ( WBC ) count to the development of cardiovascular disease ( CVD ) , including coronary heart disease , stroke , peripheral arterial disease , and cardiac failure . Traditional CVD risk factors , hematocrit , and vital capacity were considered . DESIGN Prospect i ve cohort analysis with one baseline examination of relevant risk factors and 12 years of follow-up for CVD . PARTICIPANTS AND METHODS A community-based sample ( Farmingham Offspring Study ) of 1393 men and 1401 women who were free of CVD at the onset of the study and who were between the ages of 30 and 59 years at baseline . Time-dependent multiple variable logistic regression methods were used . RESULTS There were 180 CVD events in men and 80 in women . The WBC count was correlated most strongly with the number of cigarettes smoked per day , hematocrit , and vital capacity . Among nonsmoking men with WBC counts within the normal range , the age-adjusted WBC count was significantly associated with CVD and coronary heart disease incidence . For each 1.0 x 10(9)/L-cell difference in WBC count , the CVD risk increased 32 % . In women , each 1.0 x 10(9)/L-cell increment in WBC count was associated with a 17 % increase in CVD risk , but only in smokers , and the relationship was not statistically significant after adjustment for relevant risk factors . CONCLUSIONS The degree of elevation of WBC count within the normal range is a marker for increased risk of CVD that is partially explained by cigarette smoking . Future studies should include differential WBC determinations to assess their association with CVD BACKGROUND Several studies have observed high plasma levels of homocysteine among patients with coronary heart disease ( CHD ) . The only prospect i ve study was based on US physicians , and concluded that homocysteine was associated with subsequent myocardial infa rct ion ( MI ) . However , the association was limited to those above a threshold level of homocysteine . METHODS We conducted a nested case-control study among the 21,826 subjects , aged 12 - 61 years , who were surveyed in the municipality of Tromsø , Norway . Among those free from MI at the screening , 123 later developed CHD . Four controls were selected for each case . RESULTS Level of homocysteine was higher in cases than in controls ( 12.7 + /- 4.7 versus 11.3 + /- 3.7 mumol/l ( mean + /- SD ) ; P = 0.002 ) . The relative risk for a 4 mumol/l increase in serum homocysteine was 1.41 ( 95 % confidence interval ( CI ) : 1.16 - 1.71 ) . Adjusting for possible confounders reduced the relative risk to 1.32 ( 95 % CI : 1.05 - 1.65 ) . There was no threshold level above which serum homocysteine is associated with CHD events . CONCLUSIONS In the general population serum total homocysteine is an independent risk factor for CHD with no threshold level Several studies have found that the homocysteine plasma level is associated with cardiovas cular disease . The authors previously described a relationship between concentrations of fibrinogen and other inflammation-sensitive plasma proteins , namely , α1-antitrypsin , cerulo plasmin , haptoglobin , and orosomucoid ( α 1-acid glucoprotein ) and the incidence of myocardial infa rct ion ( MI ) . Whether levels of these proteins are related to homocysteine has not been clarified . The aim of this study was to investigate whether a supposed relationship between homocysteine in plasma and the occurrence of MI is modified by these inflammation-sensitive proteins . A nested case-control study was design ed , comprising 241 cases of MI , with a mean age of 48 years at baseline , and 241 controls matched for age , month of examination , and duration of follow-up . The mean homocysteine concentration did not differ between cases and controls and there was no association between the baseline homocysteine level and the time lapse before the occurrence of the MI . For the cases , there was no correlation between homo cysteine and any of the measured proteins , but for the controls , homocysteine was weakly but significantly negatively correlated to haptoglobin and ceruloplasmin and slightly positively correlated to albumin . For the separated groups of cases and controls there was no associa tion between the number of inflammation-sensitive proteins in the top quartiles and homo cysteine concentration . In this population -based , prospect i ve cohort study the occurrence of MI had no relationship to homocysteine baseline plasma level . Furthermore , there was no strong association between homocysteine and the concentrations of any of these inflamma tion-sensitive proteins CONTEXT Controversy exists as to whether lipoprotein(a ) , a lipoprotein with homology to plasminogen , is a clinical ly meaningful cardiovascular risk marker in women . There is also poor agreement among lipoprotein(a ) levels obtained by different assays . OBJECTIVE To determine the association of lipoprotein(a ) levels , measured with an assay independent of apolipoprotein(a ) isoform size , with the incidence of future cardiovascular events . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve study of 27,791 initially healthy women in the Women 's Health Study , enrolled between November 1992 and July 1995 and followed up for 10 years . Lipoprotein(a ) level was measured in blood sample s obtained at baseline with an assay independent of apolipoprotein(a ) isoform size . MAIN OUTCOME MEASURE Hazard ratios ( HRs ) for first-ever major cardiovascular events ( nonfatal myocardial infa rct ion , nonfatal cerebrovascular event , coronary revascularization , or cardiovascular deaths ) . RESULTS During follow-up , there were 899 incident cardiovascular events . After adjusting for age , smoking , blood pressure , body mass index , total cholesterol , high-density lipoprotein cholesterol , diabetes , hormone use , C-reactive protein , and r and omization treatment groups , women in the highest quintile of lipoprotein(a ) ( > or = 44.0 mg/dL ) were 1.47 times more likely ( 95 % CI , 1.21 - 1.79 ; P for trend < .001 ) to develop cardiovascular events than women in the lowest quintile ( < or = 3.4 mg/dL ) . This association , however , was due almost entirely to a threshold effect among those with the highest lipoprotein(a ) levels . After adjusting for all of the variables listed above , the HR associated with lipoprotein(a ) levels exceeding the 90th percentile ( > or = 65.5 mg/dL ) was 1.66 ( 95 % CI , 1.38 - 1.99 ) ; 95th percentile ( > or = 83 mg/dL ) , 1.87 ( 95 % CI , 1.50 - 2.34 ) ; and 99th percentile ( > or = 130.7 mg/dL ) , 1.99 ( 95 % CI , 1.32 - 3.00 ) , with almost no risk gradient at lower levels . Associations were strongest among women with low-density lipoprotein cholesterol ( LDL-C ) above the median level . In this subgroup , the adjusted HR associated with lipoprotein(a ) levels exceeding the 90th percentile was 1.81 ( 95 % CI , 1.48 - 2.23 ) ; 95th percentile , 1.93 ( 95 % CI , 1.51 - 2.48 ) ; and 99th percentile , 1.93 ( 95 % CI , 1.21 - 3.05 ) ( P value for interaction with LDL-C = .001 ) . CONCLUSIONS In this cohort of initially healthy women , extremely high levels of lipoprotein(a ) ( > or = 90th percentile ) , measured with an assay independent of apolipoprotein(a ) isoform size , were associated with increased cardiovascular risk , particularly in women with high levels of LDL-C. However , the threshold and interaction effects observed do not support routine measurement of lipoprotein(a ) for cardiovascular stratification in women A 6-year follow-up based on an arterial morphology classification defined with an ultrasound assessment of carotid and femoral artery bifurcations was conducted on 2322 asymptomatic subjects . Four morphology classes were considered . When 2000 subjects ( 86 % of total subjects ; 1124 males , 876 females ) completed a 6-year follow-up , the study was terminated . At 6 years , no cardiovascular events were observed in subjects who were in class I ( 80.05 % of the population sample ) at inclusion ; there were 69 events in classes II , III , and IV ( 19.95 % of the population ; incidence , 17.3 % ) ; 59 events , including the five deaths , occurred in classes III and IV ( 10.85 % of the population ) , producing an event incidence of 27.2 % . The increased event rate in classes II , III , and IV was significant ( log-rank test ; P < .05 , P < .025 , and P < .025 , respectively ) . Thus , the arterial morphology classification identified 19.95 % of the population ( subjects in classes II , III , and IV ) in which all events occurred . There was a higher ( P < .05 ) rate of progression of altered arterial morphology in 6 years in classes III ( 26.5 % of subjects progressed ) and IV ( 41.9 % progressed ) than in classes I and II . The total number of cigarette-years was higher ( P < .05 ) in classes II , III , and IV than in class I. In conclusion , the ultrasound-based arterial classification was useful in selecting from the population sample 80.05 % of subjects ( class I ) who remained event-free for 6 years . All events occurred in class II , III , and IV subjects ( 19.95 % ) , and all five deaths ( 0.25 % of the population ) occurred in classes III and IV ( 10.85 % of the sample ) OBJECTIVE To examine the relationship between elevated levels of lipoprotein(a ) [ Lp(a ) ] and coronary heart disease ( CHD ) risk in a prospect i ve study . DESIGN Nested case-control study . The cohort consisted of participants in the Lipid Research Clinics Coronary Primary Prevention Trial . SETTING Lipid research clinics . PARTICIPANTS The Lipid Research Clinics Coronary Primary Prevention Trial participants ( n = 3806 ) were men , aged 35 to 59 years , with plasma cholesterol levels of 6.85 mmol/L ( 265 mg/dL ) or greater , low-density lipoprotein cholesterol levels of 4.91 mmol/L ( 190 mg/dL ) or greater , and triglyceride levels less than 3.39 mmol/L. Subjects were r and omly assigned to either cholestyramine or placebo treatment . The Lp(a ) levels were measured in plasma sample s obtained prior to r and omization in 233 cases ( participants who developed CHD in the course of the study ) and 390 matched CHD-free controls . A total of 96.95 % of the subjects were white , 2.25 % were black , and 0.80 % were of other race . MAIN OUTCOME MEASURE Coronary heart disease ( either fatal or nonfatal ) events during a follow-up of 7 to 10 years . RESULTS The Lp(a ) levels were significantly higher ( 21 % ) in cases than in controls ( 23.7 mg/dL [ 0.59 mmol/L ] and 19.5 mg/dL [ 0.49 mmol/L ] , respectively ; P < .02 ) . This difference was still statistically significant ( P < .01 ) after controlling for age , body mass index , cigarette smoking , blood pressure , low-density lipoprotein cholesterol level , and high-density lipoprotein cholesterol level . When subjects were divided by treatment , both cholestyramine-treated and placebo-treated CHD subjects had Lp(a ) levels 20 % to 22 % greater than their matched controls . However , possibly because of smaller sample sizes , these differences were no longer statistically significant . CONCLUSIONS Our data are consistent with the concept that an elevated Lp(a ) level is an independent risk factor for CHD in hypercholesterolemic white men BACKGROUND While meta-analyses of prospect i ve studies have established that plasma levels of several hemostatic variables are associated with the risk of coronary heart disease ( CHD ) , these have been suggested to be acute-phase reactant proteins . This study examines their associations with inflammatory markers [ C-reactive protein ( CRP ) and interleukin-6 ( IL-6 ) ] and the effect of adjustment on their associations with CHD risk . METHODS AND RESULTS In a nested case-control study , 247 CHD cases and 473 controls were matched for age and sex from 10 529 men and women in the Fletcher Challenge cohort . Plasma levels of all hemostatic variables except von Willebr and factor ( VWF ) and lipoprotein ( a ) [ Lp(a ) ] showed significant associations with CRP and IL-6 . Fibrinogen , VWF , tissue plasminogen activator antigen ( t-PA ) , D-dimer , Lp(a ) , CRP and IL-6 levels were significantly associated with risk of CHD . After adjustment for conventional risk factors , CRP , D-dimer and IL-6 levels were significantly associated with risk of CHD . On further adjustments for the other six hemostatic and inflammatory variables these associations were reduced , but remained significant for D-dimer and IL-6 ; odds ratios ( 95 % CI ) , comparing the highest to lowest third , were 3.10 ( 1.25 - 7.67 ) and 2.79 ( 1.11 - 6.99 ) , respectively . CONCLUSION The associations of plasma levels of some hemostatic variables ( fibrinogen , VWF , t-PA and Lp(a ) ; but not fibrin D-dimer ) with CHD risk are attenuated when inflammatory markers ( CRP and IL-6 ) as well as conventional risk factors are included in multivariable analyses . D-dimer and IL-6 each have the potential to increase the prediction of CHD , in addition to conventional risk factors OBJECTIVES To study serum homocysteine concentration for its prediction of major coronary heart disease events amongst women . DESIGN A case-control study nested within a follow-up study . Subjects . A total of 74 and 75 major coronary events ( coronary deaths or nonfatal myocardial infa rct ion ) which occurred in women with and without known heart disease , respectively , during a 13-year follow-up and two individually matched controls per case . Main outcome measure . Major coronary event . RESULTS Amongst women with baseline heart disease , the relative risk ( 95 % CI ) of such events , adjusted for age , smoking , hypertension , diabetes , serum cholesterol and body mass index , was 3.32 ( 1.05 - 10.5 ) in the highest homocysteine quintile compared with the lowest quintile . Amongst women free of heart disease at baseline , the corresponding relative risk value was 0.77 ( 0.24 - 2.45 ) . CONCLUSIONS This prospect i ve study support the hypothesis that homocysteine is a risk factor for coronary events in women with heart disease A nested case-control study was undertaken involving men participating in the Multiple Risk Factor Intervention Trial ( MRFIT ) . Serum sample s from 712 men , stored for upto 20 years , were analysed for homocyst(e)ine . Cases involved non-fatal myocardial infractions , identified through the active phase of the study , which ended on February 28 , 1982 , and deaths due to coronary heart disease , monitored through 1990 . The non-fatal myocardial infa rct ion occurred within 7 years of sample collection , whereas the majority of coronary heart disease deaths occurred more than 11 years after sample collection . Mean homocyst(e)ine concentrations were in the expected range and did not differ significantly between case patients and control subjects : myocardial infa rct ion cases , 12.6 micromol/L ; myocardial infa rct ion controls , 13.1 micromol/L ; coronary heart disease death cases , 12.8 micromol/L ; and coronary heart disease controls , 12.7 micromol/L. Odds ratios versus quartile 1 for coronary heart disease deaths and myocardial infa rct ions combined were as follows : quartile 2 , 1.03 ; quartile 3 , 0.84 ; and quartile 4 , 0.92 . Thus , in this prospect i ve study , no association of homocyst(e)ine concentration with heart disease was detected . Homocyst(e)ine levels were weakly associated with the acute-phase ( C-reactive ) protein . These results are discussed with respect to the suggestion that homocyst(e)ine is an independent risk factor for heart disease This report concerns the relationship between baseline levels of fasting blood glucose ( FBG ) in non-diabetics and the subsequent 17-year incidence of coronary heart disease ( CHD ) , stroke and all-cause mortality . In 1963 , 973 men aged 50 years were recruited from a general Swedish urban population for a prospect i ve study of risk factors for CHD . Eight hundred and fifty-five ( 88 % ) men agreed to participate and have been observed for 17 years . The 832 men who had no history of myocardial infa rct ion , stroke , diabetes mellitus or who had a fasting blood glucose below 7.0 mmol/l at baseline were selected for this analysis . CHD occurred in 106 men , 35 developed a stroke and 137 died during follow-up . When quintiles and deciles of the FBG distribution were considered , no trend of 17-year incidence of CHD , stroke or death was apparent . However , for men with an FBG above the 95th percentile ( greater than 5.7 mmol/l ) a non-significant trend towards increasing risk was indicated Previous studies have reported total leukocyte count to be a risk factor for coronary heart disease . The pattern of association between each class of leukocytes and the onset of the disease was investigated in the Paris Prospect i ve Study II . The study population consisted of 3,779 male French employees aged 29 - 52 years working in the Paris area and recruited between 1980 and 1985 ( end of follow-up : June 1989 ) . A high monocyte count was strongly associated with the risk of coronary heart disease after adjustment for tobacco use and the other classical risk factors for the disease . The monocyte-macrophage is known to play an important part in the development of atherosclerosis . A high monocyte count seems to predict the premature occurrence of a coronary event in middle-aged men BACKGROUND There has been interest in recent years in whether additional , and in particular novel , risk factors or blood markers , such as C-reactive protein , can enhance existing coronary heart disease ( CHD ) prediction models . METHODS Using a series of case-cohort studies , the prospect i ve Atherosclerosis Risk in Communities ( ARIC ) Study assessed the association of 19 novel risk markers with incident CHD in 15,792 adults followed up since 1987 - 1989 . Novel markers included measures of inflammation , endothelial function , fibrin formation , fibrinolysis , B vitamins , and antibodies to infectious agents . Change in the area under the receiver operating characteristic curve ( AUC ) was used to assess the additional contribution of novel risk markers to CHD prediction beyond that of traditional risk factors . RESULTS The basic risk factor model , which included traditional risk factors ( age , race , sex , total and high-density lipoprotein cholesterol levels , systolic blood pressure , antihypertensive medication use , smoking status , and diabetes ) , predicted CHD well , as evidence d by an AUC of approximately 0.8 . The C-reactive protein level did not add significantly to the AUC ( increase in AUC of 0.003 ) , and neither did most other novel risk factors . Of the 19 markers studied , lipoprotein-associated phospholipase A(2 ) , vitamin B(6 ) , interleukin 6 , and soluble thrombomodulin added the most to the AUC ( range , 0.006 - 0.011 ) . CONCLUSIONS Our findings suggest that routine measurement of these novel markers is not warranted for risk assessment . On the other h and , our findings reinforce the utility of major , modifiable risk factor assessment to identify individuals at risk for CHD for preventive action Background The summarized importance of haemostatic and metabolic variables ( insulin , lipids including lipoprotein ( a ) [ Lp(a ) ] and leptin ) in predicting first myocardial infa rct ion , as well as possible interactions among these variables , have not been reported . Design A prospect i ve case-control study nested within the Northern Sweden Health and Disease Cohort . Methods Sixty-two men diagnosed with a first myocardial infa rct ion were sex- and age-matched with 124 controls . Conditional logistic regression was conducted including established risk factors , plasma levels of plasminogen activator inhibitor-1 ( PAI-1 ) , tissue plasminogen activator ( tPA ) mass concentration , von Willebr and factor , insulin , proinsulin , specific insulin , apolipoprotein A-I ( apo A-I ) , Lp(a ) , and leptin . Interaction analysis was also performed for tPA , apo A-I , Lp(a ) , leptin and proinsulin . Results Smoking , low plasma levels of apo A-I and high plasma levels of cholesterol , Lp(a ) , tPA , PAI-1 , proinsulin and leptin were associated with myocardial infa rct ion in univariate conditional logistic regression analysis . High tPA [ odds ratio ( OR ) , 21.3 ; 95 % confidence interval ( CI ) , 2.04 - 222 ] and Lp(a ) ( OR , 7.21 ; 95 % CI , 1.31 - 39.8 ) and low apo A-I ( OR , 0.15 ; 95 % CI , 0.02 - 0.93 ) remained significant risk determinants in multivariate analysis with smoking habits , body mass index , hypertension , cholesterol , and diabetes included as covariates . There were non-significant synergic interactions between high Lp(a ) and leptin and tPA , respectively , and between high Lp(a ) and low apo A-I. Conclusion Plasma levels of tPA , Lp(a ) , and apo A-I are independently associated with subsequent development of a first myocardial infa rct ion in men BACKGROUND Elevated total plasma homocysteine ( tHcy ) level is a risk factor for occlusive disease in the coronary , cerebral , and peripheral vessels and is related to several lifestyle factors associated with cardiovascular disease ( CVD ) . OBJECTIVE To examine the association of a single tHcy measurement on subsequent hospitalizations due to CVD . METHODS A population -based prospect i ve cohort study was conducted from April 1 , 1992 , to May 31 , 1998 ( mean follow-up , 5.3 years ) in western Norway . The study included 17 361 individuals aged 40 to 42 or 65 to 67 years at baseline . Main outcome measure was CVD as the main hospital discharge diagnosis or coronary revascularization procedures ( denoted " CVD hospitalizations " ) during follow-up ( n = 1275 ) . RESULTS At baseline , participants with preexisting CVD had higher mean tHcy values than individuals without CVD . Risk of CVD hospitalizations increased significantly with increasing baseline tHcy only in the oldest age group . Here , multiple risk factor-adjusted hospitalization rate ratios in 5 tHcy categories ( < 9 , 9 - 11.9 , 12 - 14.9 , 15 - 19.9 , and > or=20 micromol/L [ to convert tHcy to milligrams per liter , divide by 7.397 ] ) were as follows : 1 ( reference level ) , 1.00 , 1.34 , 1.67 , and 1.94 , respectively ( P for trend < .001 ) . The relation between tHcy level and CVD hospitalizations was significantly stronger among individuals with preexisting CVD than those without ( hospitalization rate ratio per 5-micromol/L tHcy increment , 1.29 vs 1.10 ; P for interaction,.02 ) . CONCLUSIONS Plasma tHcy level is a strong predictor of CVD hospitalizations only in elderly individuals , and especially among those with preexisting CVD . Our findings are compatible with the theory that tHcy interacts with conventional CVD risk factors to provoke the acute event of CVD Previous studies have shown an association between serum C-reactive protein ( CRP ) and cardiovascular disease ( CVD ) risk . The roles of interleukin-6 ( IL-6 ) and tumor necrosis factor alpha ( TNFalpha ) are less well established . The aim of the present study was to analyze the associations of CRP , IL-6 and TNFalpha with incident coronary heart disease ( CHD ) events , CVD events , and total mortality . A r and om population sample , including men and women aged 25 - 64 years was examined in Finl and in 1992 . The sample size was 7,927 and 6,051 ( 76 % ) participated . The cohort was followed up until the end of 2001 . During the follow-up , 151 incident CHD events , 205 CVD events and 183 deaths from any cause were observed . A stratified r and om sub sample ( n=313 ) was used as the comparison group . After adjustment for conventional CVD risk factors , CRP showed a significant association with CHD risk in men ( HR=2.39 , 1.08 - 5.28 , comparing fourth quartile to the first quartile ) . This association remained significant after further adjustment for TNFalpha . TNFalpha also was a significant predictor of CHD among men , but the association was nonlinear ( HR=2.21 , 1.18 - 4.14 comparing the three upper quartiles to the first quartile ) . Further adjustment for CRP did not change this association substantially . Both CRP and TNFalpha predicted also all CVD events and total mortality among men . Among women the findings were nonsignificant . In conclusion , CRP and TNFalpha were significant , independent predictors of CHD and CVD events and total mortality among men . These findings provide further support to the important role of inflammation in the pathogenesis of CVD OBJECTIVE The purpose s of this study were to examine the repeatability of the findings of coronary artery calcification ( CAC ) measured with CT on repeated scans , to estimate 95 % repeatability limits for CAC , and to use these limits to quantify detectable change in CAC over time . SUBJECTS AND METHODS The Multi-Ethnic Study of Atherosclerosis is a prospect i ve cohort study with 6,814 participants 45 - 84 years old and free of clinical cardiovascular disease at enrollment . Agreement for presence of CAC was assessed for 6,742 participants who had baseline replicate scans on which a CAC score of 0 indicated no coronary calcification . Among 3,380 participants with baseline CAC , the 95 % repeatability limits were established with a quantile regression model . Detectable change in CAC during follow-up was defined by an increase or decrease beyond the baseline repeatability limit . RESULTS At baseline , 274 ( 4.1 % ) of the rescan pairs were discordant ( presence or absence of CAC ) . Greater body mass index was associated with a discordant pair ( trend , p < 0.05 ) . The upper 95 % repeatability limits were ( 0.17 x Agatston score ) + ( 4.89 x sq rt(Agatston score ) ) + ( 0.44 x body mass index ) - 10.84 for Agatston score and ( 0.16 x volumetric calcium score ) + ( 4.30 x sq rt(volumetric calcium score ) ) + ( 0.23 x body mass index ) - 5.00 for volumetric calcium score . Rescan repeatability was comparable for electron beam and 4-MDCT scanners . At 2.5 years of average follow-up ( range , 0.9 - 5.0 years ) , a detectable increase in Agatston and volumetric calcium scores was observed in 1,027 ( 36.3 % ) and 1,020 ( 36.0 % ) , respectively , of 2,832 participants with baseline CAC . CONCLUSION The repeatability limits derived can be used to evaluate whether an increase in CAC score exceeds that expected from measurement error alone The association between leukocyte count and subsequent risk of major coronary heart disease events was examined using data from three prospect i ve cohort studies --two from the United States and one from Great Britain . A total of 28,181 middle-aged men were followed for 6 - 12 years . A total of 1,768 men had a nonfatal myocardial infa rct ion or died of coronary heart disease . In all three cohorts , there was a positive , statistically significant relation between baseline leukocyte count and risk of subsequent major coronary heart disease events after adjustment for age , serum total cholesterol , diastolic blood pressure , and number of cigarettes smoked per day ( relative odds = 1.32 ( p less than 0.0001 ) , 1.15 ( p = 0.0001 ) , and 1.14 ( p = 0.003 ) , corresponding to a 2,000/mm3 difference in leukocyte count ) . The associations persisted when all nonsmokers ( former smokers plus never smokers ) and never smokers alone were considered and when those with evidence of preexisting coronary heart disease at baseline were excluded . Leukocyte count appears to be an indicator of a person 's future risk of major coronary heart disease events Abstract Objective : To determine whether a low ankle brachial pressure index is associated with an increased risk of cardiovascular events and death , and whether the prediction of such events could be improved by including this index . Design : Cohort study . Setting : 11 practice s in Edinburgh , Scotl and . Subjects : 1592 men and women aged 55–74 years selected at r and om from the age-sex registers of 11 general practice s and followed up for 5 years . Main outcome measures : Incidence of fatal and non-fatal cardiovascular events and all cause mortality . Results : At baseline 90 ( 5.7 % ) of subjects had an ankle brachial pressure index < /=0.7 , 288 ( 18.2 % ) had an index < /=0.9 , and 566 ( 35.6 % ) < /=1.0 . After five years subjects with an index < /=0.9 at baseline had an increased risk of non-fatal myocardial infa rct ion ( relative risk 1.38 , 95 % confidence interval 0.88 to 2.16 ) , stroke ( 1.98 , 1.05 to 3.77 ) , cardiovascular death ( 1.85 , 1.15 to 2.97 ) , and all cause mortality ( 1.58 , 1.14 to 2.18 ) after adjustment for age , sex , coronary disease , and diabetes at baseline . The ability to predict subsequent events was greatly increased by combining the index with other risk factors — for example , hypertensive smokers with normal cholesterol concentrations had a positive predictive value of 25.0 % , increasing to 43.8 % in subjects with a low index and decreasing to 15.6 % in those with a normal index . Conclusion : The ankle brachial pressure index is a good predictor of subsequent cardiovascular events , and improves on predictions by conventional risk factors alone . It is simple and accurate and could be included in routine screening of cardiovascular status . Key messages In this study individuals with a low ankle brachial pressure index had an increased risk of fatal and non-fatal cardiovascular events The index was a good predictor of subsequent cardiovascular events , and improved that of conventional risk factors alone The ankle brachial pressure index could be included in routine screening of cardiovascular status Individuals with a low ankle brachial pressure index require additional monitoring , and might benefit from aspirin or other secondary preventive CONTEXT Postmenopausal hormone replacement therapy ( HRT ) has been shown to elevate C-reactive protein ( CRP ) levels . Several inflammatory biomarkers , including CRP , are associated with increased cardiovascular risk . However , whether the effect of HRT on CRP represents a clinical hazard is unknown . OBJECTIVES To assess the association between baseline levels of CRP and interleukin 6 ( IL-6 ) and incident coronary heart disease ( CHD ) and to examine the relationship between baseline use of HRT , CRP , and IL-6 levels as they relate to subsequent vascular risk . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , nested case-control study of postmenopausal women , forming part of the Women 's Health Initiative , a large , nationwide , observational study . Among 75 343 women with no history of cardiovascular disease or cancer , 304 women who developed incident CHD were defined as cases and matched by age , smoking status , ethnicity , and follow-up time with 304 study participants who remained event free during a median observation period of 2.9 years . MAIN OUTCOME MEASURE Incidence of first myocardial infa rct ion or death from CHD . RESULTS Median baseline levels of CRP ( 0.33 vs 0.25 mg/dL ; interquartile range [ IQR ] , 0.14 - 0.71 vs 0.10 - 0.47 ; P<.001 ) and IL-6 ( 1.81 vs 1.47 pg/mL ; IQR , 1.30 - 2.75 vs 1.05 - 2.15 ; P<.001 ) were significantly higher among cases compared with controls . In matched analyses , the odds ratio ( OR ) for incident CHD in the highest vs lowest quartile was 2.3 for CRP ( 95 % confidence interval [ CI ] , 1.4 - 3.7 ; P for trend = .002 ) and 3.3 for IL-6 ( 95 % CI , 2.0 - 5.5 ; P for trend < .001 ) . After additional adjustment for lipid and nonlipid risk factors , both inflammatory markers were significantly associated with a 2-fold increase in odds for CHD events . As anticipated , current use of HRT was associated with significantly elevated median CRP levels . However , there was no association between HRT and IL-6 . In analyses comparing individuals with comparable baseline levels of either CRP or IL-6 , those taking or not taking HRT had similar CHD ORs . In analyses stratified by HRT , we observed a positively grade d relationship between plasma CRP levels and the OR for CHD among both users and nonusers of HRT across the full spectrum of baseline CRP . CONCLUSIONS These prospect i ve findings indicate that CRP and IL-6 independently predict vascular events among apparently healthy postmenopausal women and that HRT increases CRP . However , use or nonuse of HRT had less importance as a predictor of cardiovascular risk than did baseline levels of either CRP or IL-6 CONTEXT Research has suggested a relationship between periodontal disease and coronary heart disease ( CHD ) , but data on the association between these 2 common conditions are inconclusive due to the possibility of confounding . OBJECTIVE To evaluate the risk of CHD in persons with periodontitis , gingivitis , or no periodontal disease . DESIGN Prospect i ve cohort study . SETTING The First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study , conducted in 1982 - 1984 , 1986 , 1987 , and 1992 . PARTICIPANTS A total of 8032 dentate adults aged 25 to 74 years with no reported history of cardiovascular disease , including 1859 individuals with periodontitis , 2421 with gingivitis , and 3752 with healthy periodontal tissues . MAIN OUTCOME MEASURE First occurrence of death from CHD or hospitalization due to CHD , or revascularization procedures , obtained from death certificates and medical records , by baseline periodontal status . RESULTS During follow-up , 1265 individuals had at least 1 CHD event , including CHD fatality ( n = 468 ) or at least 1 hospitalization with a diagnosis of CHD ( n = 1022 ) , including coronary revascularization procedures ( n = 155 ) . After adjustment for known cardiovascular risk factors , gingivitis was not associated with CHD ( hazard ratio , 1.05 ; 95 % confidence interval , 0.88 - 1.26 ) , while periodontitis was associated with a nonsignificant increased risk for CHD event ( hazard ratio , 1 . 14 ; 95 % confidence interval , 0.96 - 1.36 ) . CONCLUSION This study did not find convincing evidence of a causal association between periodontal disease and CHD risk . JAMA . 2000;284:1406 - 1410 Since the excess mortality rate associated with an ankle-brachial blood-pressure index ( ABPI ) less than 0.9 was only partly explained by an excess cardiovascular mortality , we believe that leg artery disease should not only be regarded as a marker of generalised arteriosclerosis but also as a sign associated with an increased risk of premature death . 439 men who were part of a prospect i ve population study in Malmö , Sweden , were , at 68 years of age , invited to a health examination including , ABPI , carotid-artery ultrasonography , and 24 h ambulatory electrocardiographic monitoring . Cause-specific mortality and incidence of myocardial infa rct ion ( MI ) during 8 years of follow-up was compared in men with and without signs of arteriosclerotic disease . Of 60 men with an ABPI < 0.9 , 20 ( 33 % ) had angina pectoris or previous MI . Another 11 ( 18 % ) had silent ST-segment depression ( > or = 1 mm ) ; 3 ( 5 % ) had a history of stroke ; and 17 ( 28 % ) had symptom-free carotid stenosis ( > 30 % reduction of the cross-sectional diameter ) . Total mortality rate in men with no signs of arteriosclerotic disease was 19.6 per 1000 person-years and cardiac event rate ( fatal and non-fatal MI and death from chronic ischaemic heart disease was 8.6 per 1000 person-years ) . Leg artery disease , carotid stenosis , and ischaemic heart disease were in a univariate analysis all associated with an increased cardiac event rate and an increased total mortality rate . In a multivariate analysis an ABPI less than 0.9 was associated with a 2.4 times higher total mortality ( 95 % CI 1.5 - 3.9 ) and a 2.0 times higher cardiac event rate ( 1.1 - 3.9 ) . Carotid stenosis and ischaemic heart disease contributed to the risk for MI ( RR 2.1 ; 95 % CI 1.2 - 3.8 ; and 2.1 ; 1.2 - 3.9 , respectively ) , whereas no independent association with total mortality was found |
13,582 | 27,123,955 | These small trials suggest that for people with LRTI affecting tissues of the head , neck , anus and rectum , HBOT is associated with improved outcome .
HBOT also appears to reduce the chance of ORN following tooth extraction in an irradiated field .
There was no such evidence of any important clinical effect on neurological tissues .
The application of HBOT to selected participants and tissues may be justified . | BACKGROUND Cancer is a significant global health problem .
Radiotherapy is a treatment for many cancers and about 50 % of people having radiotherapy will be long-term survivors .
Some will experience late radiation tissue injury ( LRTI ) developing months or years later .
Hyperbaric oxygen therapy ( HBOT ) has been suggested as a treatment for LRTI based upon the ability to improve the blood supply to these tissues .
It is postulated that HBOT may result in both healing of tissues and the prevention of problems following surgery .
OBJECTIVES To assess the benefits and harms of HBOT for treating or preventing LRTI . | PURPOSE Comparison of quality of life ( QoL ) and side effects in a r and omized trial for early hyperbaric oxygen therapy ( HBOT ) after radiotherapy ( RT ) . METHODS AND MATERIAL S From 2006 , 19 patients with tumor originating from the tonsillar fossa and /or soft palate ( 15 ) , base of tongue ( 1 ) , and nasopharynx ( 3 ) were r and omized to receive HBOT or not . HBOT consisted of 30 sessions at 2.5 ATA ( 15 msw ) with oxygen breathing for 90 min daily , 5 days per week , applied shortly after the RT treatment was completed . As of 2005 , all patients received vali date d question naires ( i.e. , the European Organization for Research and Treatment of Cancer [ EORTC ] QLQ-C30 , EORTC QLQ Head and Neck Cancer Module ( H&N35 ) , Performance Status Scale ) : before treatment ; at the start of RT treatment ; after 46 Gy ; at the end of RT treatment ; and 2 , 4 , and 6 weeks and 3 , 6 , 12 , and 18 months after follow-up . RESULTS On all QoL items , better scores were obtained in patients treated with hyperbaric oxygen . The difference between HBOT vs. non-HBOT was significant for all parameters : EORTC H&N35 Swallowing ( p = 0.011 ) , EORTC H&N35 Dry Mouth ( p = 0.009 ) , EORTC H&N35 , Sticky Saliva ( p = 0.01 ) , PSS Eating in Public ( p = 0.027 ) , and Pain in Mouth ( visual analogue scale ; p < 0.0001 ) . CONCLUSIONS Patients r and omized for receiving hyperbaric oxygen after the RT had better QoL scores for swallowing , sticky saliva , xerostomia , and pain in mouth Although hyperbaric oxygen is used to treat chronic radiation tissue injury , clinical evidence supporting its efficacy has been limited to date . The authors report prospect ively collected patient outcomes from a single center 's large experience using hyperbaric oxygen to treat chronic radiation injury The aim of this study was to evaluate the effect of hyperbaric oxygen therapy ( HBOT ) on microvascular tissue and cell proliferation in the oral mucosa . Twenty patients , aged 51 - 78 years , were allocated r and omly to a treatment or a control group . All had a history of radiotherapy ( 50 - 70 Gy ) to the orofacial region 2 - 6 years previously . Tissue sample s were taken from the irradiated buccal oral mucosa before HBOT and at 6 months after treatment . In the control group , tissue sample s were taken on two occasions , 6 months apart . The sample s were subjected to immunohistochemistry staining : double staining with CD31 and D2 - 40 for microvessels , or Ki-67 for the analysis of cell proliferation . Blood vessel density and area were significantly increased after HBOT ( P=0.002 - 0.041 ) . D2 - 40-positive lymphatic vessels were significantly increased in number and area in the sub-epithelial area ( P=0.002 and P=0.019 , respectively ) . No significant differences were observed in the control group . There were no significant differences in Ki-67-expressing epithelial cells between the two groups . It is concluded that the density and area of blood and lymphatic vessels in the irradiated mucosa are increased by HBOT 6 months after therapy . Epithelial cell proliferation is not affected by HBOT Surgical treatment of malignancies in the oral cavity and subsequent radiotherapy often result in an anatomic and physiological oral condition unfavorable for prosthodontic rehabilitation . The objective of this prospect i ve study was to assess the effect of hyperbaric oxygen therapy on treatment outcome ( condition of peri-implant tissues , implant survival , oral functioning and quality of life ) of prosthodontic rehabilitation with implant-retained lower dentures in radiated head and neck cancer patients 6 weeks and 1 year after placing the new dentures . The treatment outcome was assessed in a group of 26 head neck cancer patients who were subjected to radiotherapy after tumour surgery . St and ardized question naires were completed and clinical and radiographic assessment s were performed . After r and omization , endosseous Brånemark implants were placed in the anterior part of the m and ible either under antibiotic prophylaxis ( 13 patients ) or under antibiotic prophylaxis combined with pre and postsurgery hyperbaric oxygen ( HBO ) treatment ( 13 patients ) . In the HBO and non-HBO group eight implants ( implant survival 85.2 % ) and three implants ( implant survival 93.9 % ) were lost , respectively . Peri-implant tissues had a healthy appearance in both groups . Osteoradionecrosis developed in one patient in the HBO group . All patients functioned well with their implant-retained lower denture . The quality of life related to oral functioning and denture satisfaction were improved to a comparable extent in the HBO and non-HBO group . Implant-retained lower dentures can improve the quality of life related to oral functioning and denture satisfaction in head and neck cancer patients . Adjuvant hyperbaric oxygen therapy could not be shown to enhance implant survival in radiated m and ibular jaw bone Significant challenges are faced by the oral and and a variety of donor sites available to the surgical maxillofacial reconstructive surgeon . As health care professionals , we are in a constant search for excellence in patient care , education , and research . The objective of this issue of the Oral and Maxillofacial Surgery Clinics of North America is to address the needs of a continually evolving specialty , combined with the stated goal of expected excellence . Rehabilitation of the facial structures is a complex task . Optimal treatment requires the achievement of multiple reconstructive goals : oral competence , effective mastication , functional deglutition , preservation of speech , and an acceptable cosmetic appearance . When we assess the cosmetic needs of a patient , we should address symmetry , color , texture , strength , sensibility , and motor innervation of the tissues to be replaced . Appropriate choice of the harvest site is key in the decision process . We can reach these stated objectives through a systematic prospect i ve analysis by using outcome measures . The goal of academic surgery is to translate research into education and delivery of care . Successful clinical outcomes can be applied to maximize patient management . The success of translational research in the area of reconstruction has result ed in a plethora of Purpose : Analysis of the feasibility and effect of hyperbaric oxygen treatment ( HBO ) on cognitive functioning in patients with cognitive disorders after irradiation of the brain . Patients and Method : Seven patients with cognitive impairment after brain irradiation , with an interval of at least 1.5 years after treatment , were treated with 30 sessions of HBO in a phase I – II study . A comprehensive neuropsychological test battery was performed before treatment , at 3 and 6 months thereafter . Patients were r and omized into an immediate treatment group and a delayed treatment group . The delayed group had a second neuropsychological test at 3 months without treatment in that period and started HBO thereafter . Results : All eligible patients completed the HBO treatment and the extensive neuropsychological testing . One out of seven patients had a meaningful improvement in neuropsychological functioning . At 3 months there was a small , but not significant benefit in neuropsychological performance for the group with HBO compared to the group without HBO treatment . Six out of seven patients eventually showed improvement after HBO in one to nine ( median 2.5 ) of the 31 tests , although without statistical significance . Conclusion : HBO treatment was feasible and result ed in a meaningful improvement of congitive functioning in one out of seven patients . Overall there was a small but not significant improvement . Hintergrund : Es wurden die Durchführbarkeit und Wirksamkeit der hyperbaren Oxygenierung ( HBO ) auf die Gehirnfunktion bei Patienten mit kognitiven Störungen nach Hirnbestrahlung untersucht . Patientengut und Method e : In einer Phase-I/II-Studie wurden sieben Patienten mit kognitiven Störungen nach einem minimalen Intervall von 1,5 Jahren 30 HBO-Beh and lungen unterzogen . Neuropsychologische Tests wurden vor HBO sowie 3 und 6 Monate nach Abschluss der Beh and lung durchgeführt . Patienten wurden r and omisiert in eine sofortige und eine späte Beh and lungsgruppe . Die späte Beh and lungsgruppe wurde nach 3 Monaten zum zweiten Mal neuropsychologisch getestet ohne zwischenzeitliche HBO-Beh and lung . Nach diesem zweiten Test begann in dieser Gruppe die HBO . Ergebnisse : Alle Patienten konnten die vorgeschriebene HBO-Therapie und das umfangreiche neuropsychologische Testprogramm abschließen . Einer von sieben Patienten zeigte eine bedeutsame Verbesserung der neuropsychologischen Funktion . Die HBO-Gruppe zeigte i m Vergleich zu einer nicht mit HBO beh and elten Kontrollgruppe nach 3 Monaten eine leichte , statistisch nicht signifikante Verbesserung . Bei sechs der insgesamt sieben HBO-Patienten waren Verbesserungen nachweisbar in einem bis neun ( median 2,5 ) der 31 Tests , die statistisch jedoch nicht signifikant waren . Schlussfolgerung : HBO ist bei Patienten nach Hirnbestrahlung durchführbar und erzielte bei einem von sieben Patienten eine bedeutsame Verbesserung der kognitiven Funktion . Insgesamt zeigte sich eine leichte , statistisch nicht signifikante Verbesserung der getesteten Hirnfunktionen AIM to evaluate the influence of HBOT to the side effect and quality of life after pelvic radiation . METHODS this is an open r and omized , parallel , prospect i ve study conducted in Department of Obstetrics and Gynecology , Oncology Division and Department of Radiotherapy . Endoscopy procedure was performed in Department of Internal Medicine and tissue biopsy in Department of Pathology Anatomy . The hyperbaric oxygen therapy ( HBOT ) was done in Dr. Mintohardjo , Navy Seal Hospital Jakarta . The side effect was measured using LENT SOMA scale ratio , the quality of life used the Karnofsky score . The difference of two mean was analyzed using student t test . RESULTS of 32 patients undergoing HBOT and 33 patients as control , the ratio of ASE of control group was 44.1+/-28.2 % , HBOT group was 0.7+/-30.1 % ; p<0.001 ; the LSE of control group was 33.6+/-57.6 % , HBOT group was -19.6+/-69.4 % ; p=0.008 . Quality of life of control group after intervention was 4.5+/-10.7 % ; HBOT group was 19.7+/-9.6 % ; p < 0.001 . After 6 months of intervention the quality of life was 2.5+/-16.1 % in the control group , and HBOT group was 15.2+/-14.7 % ; p = 0.007 . CONCLUSION the study showed that HBOT decreased acute and late side effect , also improved the quality of life of patients with proctitis radiation The aim of this study was to evaluate the effect of hyperbaric oxygen therapy ( HBOT ) on vascular function and tissue oxygenation in irradiated facial skin and gingival mucosa . Twenty-two patients , aged 51 - 90 years , were r and omly allocated to a treatment or control group . All had a history of radiotherapy ( 50 - 70 Gy ) to the orofacial region 2 - 20 years previously . Skin and mucosal perfusion were recorded with laser Doppler flowmetry ( LDF ) . Tissue oxygenation was recorded by transcutaneous oximetry ( TcPO(2 ) ) . Measurements were taken before HBOT and 3 and 6 months after a mean of 28 HBOT sessions ( partial pressure of oxygen of 240 kPa for 90 min ) . For control subjects , measurements were taken on two occasions 6 months apart . After HBOT , blood flow in mucosa and skin after heat provocation increased significantly ( P < 0.05 ) . TcPO(2 ) increased significantly in the irradiated cheek ( P < 0.05 ) , but not at reference points outside the field of radiation . There were no differences between the 3- and 6-month follow-ups . In the control group , no significant changes in LDF or TcPO(2 ) were observed . It is concluded that oxygenation and vascular capacity in irradiated facial skin and gingival mucosa are increased by HBOT . The effects persist for at least 6 months PURPOSE Persisting symptomatology after breast-conserving surgery and radiation is frequently reported . In most cases , symptoms in the breast resolve without further treatment . In some instances , however , pain , erythema , and edema can persist for years and can impact the patient 's quality of life . Hyperbaric oxygen therapy was shown to be effective as treatment for late radiation sequelae . The objective of this study was to assess the efficacy of hyperbaric oxygen therapy in symptomatic patients after breast cancer treatment . PATIENTS AND METHODS Forty-four patients with persisting symptomatology after breast-conservation therapy were prospect ively observed . Thirty-two women received hyperbaric oxygen therapy in a multiplace chamber for a median of 25 sessions ( range , 7 - 60 ) . One hundred percent oxygen was delivered at 240 kPa for 90-min sessions , 5 times per week . Twelve control patients received no further treatment . Changes throughout the irradiated breast tissue were scored prior to and after hyperbaric oxygen therapy using modified LENT-SOMA criteria . RESULTS Hyperbaric oxygen therapy patients showed a significant reduction of pain , edema , and erythema scores as compared to untreated controls ( p < 0.001 ) . Fibrosis and telangiectasia , however , were not significantly affected by hyperbaric oxygen therapy . Seven of 32 women were free of symptoms after hyperbaric oxygen therapy , whereas all 12 patients in the control group had persisting complaints . CONCLUSIONS Hyperbaric oxygen therapy should be considered as a treatment option for patients with persisting symptomatology following breast-conserving therapy BACKGROUND A non-r and omised phase II study suggested a therapeutic effect of hyperbaric oxygen ( HBO ) therapy on arm lymphoedema following adjuvant radiotherapy for early breast cancer , justifying further investigation in a r and omised trial . METHODS Fifty-eight patients with ≥ 15 % increase in arm volume after supraclavicular ± axillary radiotherapy ( axillary surgery in 52/58 patients ) were r and omised in a 2:1 ratio to HBO ( n=38 ) or to best st and ard care ( n=20 ) . The HBO group breathed 100 % oxygen at 2.4 atmospheres absolute for 100 min on 30 occasions over 6 weeks . Primary endpoint was ipsilateral limb volume expressed as a percentage of contralateral limb volume . Secondary endpoints included fractional removal rate of radioisotopic tracer from the arm , extracellular water content , patient self- assessment s and UK SF-36 Health Survey Question naire . FINDINGS Of 53/58 ( 91.4 % ) patients with baseline assessment s , 46 had 12-month assessment s ( 86.8 % ) . Median volume of ipsilateral limb ( relative to contralateral ) at baseline was 133.5 % ( IQR 126.0 - 152.3 % ) in the control group , and 135.5 % ( IQR 126.5 - 146.0 % ) in the treatment group . Twelve months after baseline the median ( IQR ) volume of the ipsilateral limb was 131.2 % ( IQR 122.7 - 151.5 % ) in the control group and 133.5 % ( IQR 122.3 - 144.9 % ) in the treatment group . Results for the secondary endpoints were similar between r and omised groups . INTERPRETATION No evidence has been found of a beneficial effect of HBO in the treatment of arm lymphoedema following primary surgery and adjuvant radiotherapy for early breast cancer BACKGROUND Late radiation tissue injury is a serious complication of radiotherapy for patients with gynecologic malignancies . Strategies for managing pain and other clinical features have limited efficacy ; however , hyperbaric oxygen therapy ( HBO(2 ) ) may be an effective option for some patients . METHODS In a systematic review of the literature , the Ovid medline , embase , Cochrane Library , National Guidelines Clearinghouse , and Canadian Medical Association Infobase data bases were search ed to June 2009 for clinical practice guidelines , systematic review s , r and omized controlled trials , or other relevant evidence . Studies that did not evaluate soft tissue necrosis , cystitis , proctitis , bone necrosis , and other complications were excluded . RESULTS Two r and omized trials , eleven nonr and omized studies , and five supporting documents comprise the evidence base . In addition , information on the harms and safety of treatment with HBO(2 ) were reported in three additional sources . There is modest direct evidence and emerging indirect evidence that the use of HBO(2 ) is broadly effective for late radiation tissue injury of the pelvis in women treated for gynecologic malignancies . CONCLUSIONS Based on the evidence and expert consensus opinion , HBO(2 ) is likely effective for late radiation tissue injury of the pelvis , with demonstrated efficacy specifically for radiation damage to the anus and rectum;the main indication for HBO(2 ) therapy in gynecologic oncology is in the management of otherwise refractory chronic radiation injury;HBO(2 ) may provide symptomatic benefit in certain clinical setting s ( for example , cystitis , soft-tissue necrosis , and osteonecrosis ) ; and HBO(2 ) may reduce the complications of gynecologic surgery in patients undergoing surgical removal of necrosis PURPOSE To determine the efficacy and safety of hyperbaric oxygen therapy ( HBO ) for overt m and ibular osteoradionecrosis . PATIENTS AND METHODS This prospect i ve , multicenter , r and omized , double-blind , placebo-controlled trial was conducted at 12 university hospitals . Ambulatory adults with overt osteoradionecrosis of the m and ible were assigned to receive 30 HBO exposures preoperatively at 2.4 absolute atmosphere for 90 minutes or a placebo , and 10 additional HBO dives postoperatively or a placebo . The main outcome measure was 1-year recovery rate from osteoradionecrosis . Secondary end points included time to treatment failure , time to pain relief , 1-year mortality rate , and treatment safety . RESULTS At the time of the second interim analysis , based on the triangular test , the study was stopped for potentially worse outcomes in the HBO arm . A total of 68 patients were enrolled and analyzed . At 1 year , six ( 19 % ) of 31 patients had recovered in the HBO arm and 12 ( 32 % ) of 37 in the placebo arm ( relative risk = 0.60 ; 95 % CI , 0.25 to 1.41 ; P = .23 ) . Time to treatment failure ( hazard ratio = 1.33 ; 95 % CI , 0.68 to 2.60 ; P = .41 ) and time to pain relief ( hazard ratio = 1.00 ; 95 % CI , 0.52 to 1.89 ; P = .99 ) were similar between the two treatment arms . CONCLUSION Patients with overt m and ibular osteoradionecrosis did not benefit from hyperbaric oxygenation A prospect i ve r and omized trial comparing hyperbaric oxygen and systemic antibiotics in the prevention of osteoradionecrosis was presented . The results indicated , in a high-risk population who required tooth removal in irradiated m and ibles , that up-front hyperbaric oxygen produced an incidence of osteoradionecrosis of 5.4 % as compared with the antibiotic group of 29.9 % ( P = .005 ) . Hyperbaric oxygen should be considered a prophylactic measure when post-irradiation dental care involving trauma to tissue is necessary PURPOSE Cancer patients who undergo radiotherapy remain at life-long risk of radiation-induced injury to normal tissues . We conducted a r and omized , controlled , double-blind crossover trial with long-term follow-up to evaluate the effectiveness of hyperbaric oxygen for refractory radiation proctitis . METHODS AND MATERIAL S Patients with refractory radiation proctitis were r and omized to hyperbaric oxygen at 2.0 atmospheres absolute ( Group 1 ) or air at 1.1 atmospheres absolute ( Group 2 ) . The sham patients were subsequently crossed to Group 1 . All patients were re-evaluated by an investigator who was unaware of the treatment allocation at 3 and 6 months and Years 1 - 5 . The primary outcome measures were the late effects normal tissue-subjective , objective , management , analytic ( SOMA-LENT ) score and st and ardized clinical assessment . The secondary outcome was the change in quality of life . RESULTS Of 226 patients assessed , 150 were entered in the study and 120 were evaluable . After the initial allocation , the mean SOMA-LENT score improved in both groups . For Group 1 , the mean was lower ( p = 0.0150 ) and the amount of improvement nearly twice as great ( 5.00 vs. 2.61 , p = 0.0019 ) . Similarly , Group 1 had a greater portion of responders per clinical assessment than did Group 2 ( 88.9 % vs. 62.5 % , respectively ; p = 0.0009 ) . Significance improved when the data were analyzed from an intention to treat perspective ( p = 0.0006 ) . Group 1 had a better result in the quality of life bowel bother subscale . These differences were abolished after the crossover . CONCLUSION Hyperbaric oxygen therapy significantly improved the healing responses in patients with refractory radiation proctitis , generating an absolute risk reduction of 32 % ( number needed to treat of 3 ) between the groups after the initial allocation . Other medical management requirements were discontinued , and advanced interventions were largely avoided . Enhanced bowel-specific quality of life result ed |
13,583 | 26,018,758 | RESULTS For lumbopelvic pain during pregnancy , the evidence was strong for positive effects of acupuncture and pelvic belts .
The evidence was low for exercise in general and for specific stabilizing exercises .
The evidence was very limited for efficacy of water gymnastics , progressive muscle relaxation , a specific pelvic tilt exercise , osteopathic manual therapy , craniosacral therapy , electrotherapy and yoga .
For postpartum lumbopelvic pain , the evidence was very limited for clinic-based treatment concepts , including specific stabilizing exercises , and for self-management interventions for women with severe disabilities .
No specific adverse events were reported for any intervention .
The levels of evidence were strong for a positive effect of acupuncture and pelvic belts , but weak for an effect of specific exercises . | OBJECTIVE To explore the effect of physiotherapeutic interventions on pregnancy-related lumbopelvic pain . | Background This pilot r and omized controlled trial evaluated the feasibility of conducting a full scale study and compared the efficacy of exercise , spinal manipulation , and a mind-body therapy called Neuro Emotional Technique for the treatment of pregnancy-related low back pain , a common morbidity of pregnancy . Methods Healthy pregnant women with low back pain of insidious onset were eligible to enroll in the study at any point in their pregnancy . Once enrolled , they remained in the study until they had their babies . Women were r and omly allocated into one of three treatment groups using opaque envelopes . The treatment schedule paralleled the prenatal care schedule and women received individualized intervention . Our null hypothesis was that spinal manipulation and Neuro Emotional Technique would perform no better than exercise in enhancing function and decreasing pain . Our primary outcome measure was the Rol and Morris Disability Question naire and our secondary outcome measure was the Numeric Pain Rating Scale . Intention to treat analysis was conducted . For the primary analysis , regression was conducted to compare groups on the outcome measure scores . In a secondary responder analysis , difference in proportions of participants in attaining 30 % and 50 % improvement were calculated . Feasibility factors for conducting a future larger trial were also evaluated such as recruitment , compliance to study protocol s , cost , and adverse events . Results Fifty-seven participants were r and omized into the exercise ( n = 22 ) , spinal manipulation ( n = 15 ) , and Neuro Emotional Technique ( n = 20 ) treatment arms . At least 50 % of participants in each treatment group experienced clinical ly meaningful improvement in symptoms for the Rol and Morris Disability Question naire . At least 50 % of the exercise and spinal manipulation participants also experienced clinical ly meaningful improvement for the Numeric Pain Rating Scale . There were no clinical ly meaningful or statistically significant differences between groups in any analysis . Conclusions This pilot study demonstrated feasibility for recruitment , compliance , safety , and affordability for conducting a larger study in the future . Spinal manipulation and exercise generally performed slightly better than did Neuro Emotional Technique for improving function and decreasing pain , but the study was not powered to detect the between-group differences as statistically significant . Trial registration Clinical Trials.gov ( Identifier : NCT00937365 ) OBJECTIVE Pregnancy-related lumbopelvic pain is a major problem for the majority of pregnant women . Complementary medicine has been used to alleviate pain , and yoga is one of the most commonly chosen alternative methods . The objective of this study was to assess the effectiveness of Hatha yoga in the reduction of lumbopelvic pain in pregnancy . METHODS A r and omized controlled trial with 60 pregnant women ( age range , 14 - 40 years ) who reported lumbopelvic pain at 12 to 32 weeks of gestation was conducted from June 2009 to June 2011 . Pregnant women who had twin pregnancies , had medical restrictions for exercise , used analgesics , and participated in physical therapy were excluded from the study . Pregnant women were divided into two groups : the yoga group , practicing exercises guided by this method , and the postural orientation group , performing st and ardized posture orientation according to instructions provided in a pamphlet . Treatment in each group lasted 10 weeks . A visual analog scale ( VAS ) was used to measure pain intensity . Lumbar pain and posterior pelvic pain provocation tests were used to confirm the presence of pain . Statistical analysis included the Mann-Whitney test , the McNemar test , a paired Wilcoxon test , and analysis of covariance . RESULTS The median pain score was lower in the yoga group ( p<.0058 ) than the postural orientation group . Lumbar pain provocation tests showed a decreased response in relation to posterior pelvic pain provocation tests and a gradual reduction in pain intensity during 10 yoga sessions ( p<.024 ) . CONCLUSIONS The yoga method was more effective at reducing lumbopelvic pain intensity compared with postural orientation Background Previous publications indicate that acupuncture is efficient for the treatment of pelvic girdle pain , PGP , in pregnant women . However , the use of acupuncture for PGP is rare due to insufficient documentation of adverse effects of this treatment in this specific condition . The aim of the present work was to assess adverse effects of acupuncture on the pregnancy , mother , delivery and the fetus/neonate in comparison with women that received stabilising exercises as adjunct to st and ard treatment or st and ard treatment alone . Methods In all , 386 women with PGP entered this controlled , single-blind trial . They were r and omly assigned to st and ard treatment plus acupuncture ( n = 125 ) , st and ard treatment plus specific stabilising exercises ( n = 131 ) or to st and ard treatment alone ( n = 130 ) for 6 weeks . Acupuncture that may be considered strong was used and treatment was started as early as in the second trimester of pregnancy . Adverse effects were recorded during treatment and throughout the pregnancy . Influence on the fetus was measured with cardiotocography ( CTG ) before-during and after 43 acupuncture sessions in 43 women . A st and ardised computerized method to analyze the CTG reading numerically ( Oxford 8000 , Oxford , Engl and ) was used . After treatment , the women rated their overall experience of the treatment and listed adverse events if any in a question naire . Data of analgesia and oxytocin augmentation during labour , duration of labour , frequency of preterm birth , operative delivery , Apgar score , cord-blood gas/acid base balance and birth weight were also recorded . Results There were no serious adverse events after any of the treatments . Minor adverse events were common in the acupuncture group but women rated acupuncture favourably even despite this . The computerized or visually assessed CTG analyses of antenatal recordings in connection with acupuncture were all normal . Conclusion This study shows that acupuncture administered with a stimulation that may be considered strong led to minor adverse complaints from the mothers but had no observable severe adverse influences on the pregnancy , mother , delivery or the fetus/neonate Background : To compare the efficiency of transcutaneous electrical nerve stimulation ( TENS ) with those of exercise and acetaminophen for the treatment of pregnancy-related low back pain ( LBP ) during the third trimester of pregnancy . Methods : This prospect i ve study included 79 subjects ( ≥32 gestational weeks ) with visual analog scale ( VAS ) pain scores ≥5 . Participants were divided r and omly into a control group ( n = 21 ) and three treatment groups [ exercise ( n = 19 ) ; acetaminophen ( n = 19 ) ; TENS ( n = 20 ) ] . The VAS and the Rol and -Morris disability question naire ( RMDQ ) were completed before and 3 weeks after treatment to assess the impact of pain on daily activities . Results : During the study period , pain intensity increased in 57 % of participants in the control group , whereas pain decreased in 95 % of participants in the exercise group and in all participants in the acetaminophen and TENS groups . Post-treatment VAS and RMDQ values were significantly lower in the treatment groups ( p < 0.001 ) . VAS and RMDQ scores indicated a significantly greater degree of pain relief in the TENS group than in the exercise and acetaminophen groups ( p < 0.001 ) . No adverse effect of TENS application on pregnant women was observed during the study . Conclusion : TENS is an effective and safe treatment modality for LBP during pregnancy . TENS improved LBP more effectively than did exercise and acetaminophen Background . Low back and pelvic pain is common in pregnancy and postpartum , but there is no well documented effect of treatment in pregnancy . The aim of the study was to assess whether a group intervention program for pregnant women with pelvic girdle pain has any effect on pain and daily function postpartum . Methods . Pregnant women with pelvic pain between the 18th and 32nd week of gestation were invited to participate in a r and omized clinical study . Among 958 examined women , 569 ( 59 % ) fulfilled the inclusion criteria . Women r and omized to the intervention group ( n = 275 ) participated in an education program that consisted of information , ergonomics , exercises , pain management , advice for daily life movement , pelvic belt/crutches , and information about delivery . Women r and omized to the control group ( n = 285 ) were not offered any treatment , but were free to seek advice or other treatment . Clinical measures and self‐evaluated utility of the intervention were measured by a visual analogue scale 0–10 . Results . Mean debut of pelvic girdle pain in pregnancy was at week 15 . Altogether 42 % of the women reported problems with low back pain earlier , and 34 % reported a family history of pelvic girdle pain in pregnancy . Median visual analogue scale score for all activities at inclusion was 6 both in the control group and the intervention group . At 6 and 12 months postpartum the score was reduced to 1.7/1.6 and 1.1/0.9 . In the intervention group , 75 % marked a self‐evaluated utility visual analogue scale score > 7 . In the control group , 60 % had search ed for alternative treatment . Conclusions . Postpartum pelvic girdle pain improved with time both in the intervention group and the control group , but there were no statistically significant differences between the groups . Self‐evaluated utility of the intervention was , however , high in the intervention group OBJECTIVE To investigate the effect of an exercise program , including specific stabilizing exercises , on pain intensity and functional ability in women with pregnancy-related low back pain . METHODS Fifty women between 16 and 24 weeks of pregnancy were recruited at Tygerberg and Paarl Hospitals , Western Cape , South Africa . Twenty-six women were r and omized to a 10-week exercise program and 24 were r and omized as controls . RESULTS Overall , the most frequent type of back pain experienced was lumbar pain ( 36 [ 72.0 % ] ) . Pain intensity ( P=0.76 ) and functional ability ( P=0.29 ) were comparable between the groups on study entry . In the study group , there was a significant improvement in pain intensity ( P<0.01 ) and an improvement in functional ability ( P=0.06 ) at the end of the study . In the control group , there were no significant changes in pain intensity ( P=0.89 ) or functional ability ( P=0.70 ) at the end of the study . CONCLUSION A specific exercise program decreased back pain intensity and increased functional ability during pregnancy in South African women with lumbar and pelvic girdle pain Background For the moment , scientific evaluation of programs on treatment of pregnancy-related pelvic girdle and /or low back pain after delivery is hardly available with only one study with a positive result , suggesting uncertainty about the optimal approach . Investigators draw particular attention to biomedical factors but there is growing evidence that biopsychosocial factors appear to be even more important as a basis of an intervention program . Methods We studied the effectiveness of a tailor-made program with respect to biopsychosocial factors ( intervention group ) in women with pregnancy-related pelvic girdle and / or low back pain versus usual care based on a pain contingent basis ( control group ) shortly after delivery in a r and omized controlled trial . Women with severe complaints shortly after delivery were selected from a longitudinal prospect i ve cohort study ( n = 7526 ) , aim ed at pregnancy-related pelvic girdle and /or low back pain in the Netherl and s. A concealed block r and omization was performed after collecting baseline data . Research ers were blinded to treatment assignment . Outcomes were evaluated within the domains of the biopsychosocial approach . Primary outcome concerned limitations in activities ( RDQ ) . Follow-up measurements were performed 12 weeks after delivery . Results Since May 2001 until July 2003 , 869 women out of the cohort made a request for treatment by a physiotherapist , 10 days after delivery . Because of a quick recovery in two weeks time , we included only 126 women three weeks after delivery . There was a statistically significant and clinical ly relevant difference in improvement on the primary outcome ( RDQ ) between the two groups in favor of the experimental intervention . Conclusion The results favored the hypotheses . Women 's worries about their condition were major targets in the experimental intervention . The prognosis after delivery , especially in de first weeks , turned out to be favorable This study was undertaken to investigate the effects of acupuncture in low back and pelvic pain during pregnancy under real life conditions , as compared with patients undergoing conventional treatment alone . A total of 61 conventionally treated pregnant women were allocated r and omly into two groups to be treated or not by acupuncture . Twenty-seven patients formed the study group and 34 the control group . They reported the severity of pain using a Numerical Rating Scale from 0 to 10 , and their capacity to perform general activities , to work , and to walk . We also assessed the use of analgesic drugs . Women were followed up for eight weeks and interviewed five times , at two-week intervals . All women completed the study . In the study group the average pain during the study period showed a larger reduction ( 4.8 points ) than the control group ( −0.3 points ) ( P<0.0001 ) . Average pain scores decreased by at least 50 % over time in 21 ( 78 % ) patients in the acupuncture group and in five ( 15 % ) patients in the control group ( P<0.0001 ) . Maximum pain and pain at the moment of interview were also less in the acupuncture group compared with the control group . The capacity to perform general activities , to work and to walk was improved significantly more in the study group than in the control group ( P<0.05 ) . The use of paracetamol was lower in the acupuncture group ( P<0.01 ) . These results indicate that acupuncture seems to alleviate low back and pelvic pain during pregnancy , as well as to increase the capacity for some physical activities and to diminish the need for drugs , which is a great advantage during this period Study Design . A r and omized clinical trial . Objectives . To examine the effects of a treatment program focusing on specific stabilizing exercises after a 2-year follow-up period . Summary of Background Data . An individualized treatment approach with specific stabilizing exercises is shown to be effective for women with pelvic girdle pain 1 year after delivery . No previous study has examined the long-term effects of treatment for women with postpartum pelvic girdle pain . Methods . Eighty-one women with pelvic girdle pain postpartum were assigned r and omly to 2 treatment groups for 20 weeks . Patient self-reported question naires measuring pain , disability , and health-related quality of life were collected after 20 weeks of treatment and 1 and 2 years postpartum . Results . All 81 women returned the question naires for the 2-year follow-up . Sixteen were excluded from the analysis , mainly due to new pregnancies . The significant differences between the groups in functional status , pain , and physical health ( SF-36 ) were maintained 2 years after delivery . Minimal disability was found in 85 % of the specific stabilizing exercise group as compared to 47 % in the control group . The control group showed significant improvement in functional status with median change score of 6.0 ( Q1–Q3 of −12–0 ) . Minimal evening pain was reported by 68 % in the specific stabilizing exercise group versus 23 % in the control group . However , the group differences disappeared for all measures when controlling for score level 1 year after delivery by regression analysis . Conclusion . The significant differences between the groups persisted with continued low levels of pain and disability in the specific stabilizing exercise group 2 years after delivery . Significant reduction in disability was found within the control group . Those with the highest level of disability and greatest potential for improvements recovered most , regardless of intervention group Background Pregnancy-related low back pain is considered an important health problem and potentially leads to long-lasting pain and disability . Investigators draw particular attention to biomedical factors but there is growing evidence that psychosocial and social factors might be important . It prompted us to start a large cohort study ( n = 7526 ) during pregnancy until one year after delivery and a nested r and omized controlled intervention study in the Netherl and s. Methods A r and omized controlled trial ( n = 126 ) nested within a cohort study , of brief self-management techniques versus usual care for treatment of women with persisting non-specific pregnancy-related low back pain three weeks after delivery . Women in the intervention group were referred to a participating physiotherapist . Women in the usual care group were free to choose physiotherapy , guidance by a general practitioner or no treatment . Follow up took place at 3 months , 6 months and one year after delivery . Outcomes included change in limitations in activities ( RDQ ) , pain ( VAS ) , severity of main complaints ( MC ) , global feeling of recovery ( GPE ) , impact on participation and autonomy ( IPA ) , pain-related fear ( TSK ) , SF-36 , EuroQol and a cost diary . For the outcome measures , series of mixed models were considered . For the outcome variable global perceived effect ( GPE ) a logistic regression analysis is performed . Results Intention-to-treat outcomes showed a statistical significant better estimated regression coefficient RDQ -1.6 { -2.9;-0.5 } associated with treatment , as well as better IPA subscale autonomy in self-care -1.0 { -1.9;-0.03 } and TSK -2.4 { -3.8;-1.1 } but were not clinical relevant over time . Average total costs in the intervention group were much lower than in usual care , primarily due to differences in utilization of sick leave but not statistically significant . Conclusion Brief self-management techniques applied in the first 3 months after delivery may be a more viable first-line approach but further research is needed to draw inference on costs and to determine whether no care is a better option in the long term . Trial Registration [ IS RCT N08477490 Objective . To study lumbopelvic pain in women r and omized to a regular exercise program during pregnancy in comparison to women receiving st and ard antenatal care . Design . A two‐armed , two‐center , r and omized controlled trial . Setting . St Olavs Hospital , Trondheim University Hospital and Stavanger University Hospital . Population . A total of 855 pregnant women were r and omized to intervention or control groups . Methods . The intervention was a 12 week exercise program , including aerobic and strengthening exercises , conducted between 20 and 36 weeks of pregnancy . One weekly group session was led by physiotherapists , and home exercises were encouraged twice a week . The control group received st and ard antenatal care . Main outcome measures . Self‐reports of lumbopelvic pain and sick leave due to lumbopelvic pain . The data were analysed according to the “ intention‐to‐treat ” principle . Results . There were no significant differences between groups of women reporting lumbopelvic pain at 36 weeks ( 74 vs. 75 % , p=0.76 ) . The proportion of women on sick leave due to lumbopelvic pain was lower in the intervention group ( 22 % vs 31 % , p=0.01 ) . Conclusions . Exercise during pregnancy does not influence the prevalence of lumbopelvic pain , but women offered a regular exercise course seem to h and le the disorder better OBJECTIVE Women commonly experience low back pain during pregnancy . We examined whether a multimodal approach of musculoskeletal and obstetric management ( MOM ) was superior to st and ard obstetric care to reduce pain , impairment , and disability in the antepartum period . STUDY DESIGN A prospect i ve , r and omized trial of 169 women was conducted . Baseline evaluation occurred at 24 - 28 weeks ' gestation , with follow-up at 33 weeks ' gestation . Primary outcomes were the Numerical Rating Scale ( NRS ) for pain and the Quebec Disability Question naire ( QDQ ) . Both groups received routine obstetric care . Chiropractic specialists provided manual therapy , stabilization exercises , and patient education to MOM participants . RESULTS The MOM group demonstrated significant mean reductions in Numerical Rating Scale scores ( 5.8 ± 2.2 vs 2.9 ± 2.5 ; P < .001 ) and Quebec Disability Question naire scores ( 4.9 ± 2.2 vs 3.9 ± 2.4 ; P < .001 ) from baseline to follow-up evaluation . The group that received st and ard obstetric care demonstrated no significant improvements . CONCLUSION A multimodal approach to low back and pelvic pain in mid pregnancy benefits patients more than st and ard obstetric care OBJECTIVE To study osteopathic manipulative treatment of back pain and related symptoms during the third trimester of pregnancy . STUDY DESIGN A r and omized , placebo-controlled trial was conducted to compare usual obstetric care and osteopathic manipulative treatment , usual obstetric care and sham ultrasound treatment , and usual obstetric care only . Outcomes included average pain levels and the Rol and -Morris Disability Question naire to assess back-specific functioning . RESULTS Intention-to-treat analyses included 144 subjects . The Rol and -Morris Disability Question naire scores worsened during pregnancy ; however , back-specific functioning deteriorated significantly less in the usual obstetric care and osteopathic manipulative treatment group ( effect size , 0.72 ; 95 % confidence interval , 0.31 - 1.14 ; P = .001 vs usual obstetric care only ; and effect size , 0.35 ; 95 % confidence interval , -0.06 to 0.76 ; P = .09 vs usual obstetric care and sham ultrasound treatment ) . During pregnancy , back pain decreased in the usual obstetric care and osteopathic manipulative treatment group , remained unchanged in the usual obstetric care and sham ultrasound treatment group , and increased in the usual obstetric care only group , although no between-group difference achieved statistical significance . CONCLUSION Osteopathic manipulative treatment slows or halts the deterioration of back-specific functioning during the third trimester of pregnancy OBJECTIVE To investigate if water-gymnastics during pregnancy may reduce the intensity of back/low back pain and the number of days on sick-leave . METHODS A prospect i ve , r and omized study . One hundred and twenty-nine women were r and omized to participate in water-gymnastics once a week during the second half of pregnancy and 129 were r and omized to a control group . The women in both groups filled in question naires in gestational weeks 18 , 34 and within the first postpartum week . Every day from week 18 to labor they assessed the intensity of back/low back pain . RESULTS Back pain intensity increased during pregnancy . No excess risk for the pregnancy associated with water-gymnastics was observed . The women participating in water-gymnastics recorded a lower intensity of back/low back pain . The total number of days on sick-leave because of back/low back pain was 982 in the water-gymnastics group ( 124 women ) compared with 1484 in the control group ( 120 women ) . After weeks 32 33 , seven women in the water-gymnastics group compared with 17 in the control group were on sickleave because of back/ low back pain ( p=0.031 ) . CONCLUSIONS Intensity of back/low back pain increased with advancing pregnancy . There was no excess risk for urinary or vaginal infections associated with water-gymnastics . Water-gymnastics during the second half of pregnancy significantly reduced the intensity of back/ low back pain . Water-gymnastics decreased the number of women on sick-leave because of back/low back pain . Water-gymnastics during pregnancy can be recommended as a method to relieve back pain and may reduce the need for sick-leave Lower back pain and lordosis are among the most common complications during pregnancy ; their frequency in pregnant women is 4 times that in non-pregnant women [ 1 ] . The present study evaluated the effect of exercise on back pain during pregnancy . Inclusion criteria were maternal age of 20–30 years ; nulliparity ; gestational age of 16 weeks ( according to reliable last menstrual period and ultrasound confirmation in the first trimester ) ; and no regular exercise before entering the study . Exclusion criteria were any kind of systemic disorder or drug use ; any previous trauma , surgery , or damage to the spine or lower limbs ; any complications of pregnancy such as preterm labor , abortion , or pelvic pain ; and absence from the study exercise program on at least 3 occasions . All eligible women completed the Rol and –Morris question naire [ 2 ] , and lordosis was measured using a flexible ruler and the formula Θ=4 × [a rct an(2H/L ) ] ( Fig. 1 ) ; these measurements were repeated after 1 and 2 months . The participants were r and omly assigned to either the study group or the control group . In the study group ( n=15 ) , there was an initial 1-hour training session in which 7 main exercises — together with preparation and relaxation movements — were taught to the participants , who then performed 30 minutes of exercise 3 times per week Table 1 Prevalence of PAI-1 4G/5 G polymorphisms in the different groups of women studied Abstract Objectives To compare the efficacy of st and ard treatment , st and ard treatment plus acupuncture , and st and ard treatment plus stabilising exercises for pelvic girdle pain during pregnancy . Design R and omised single blind controlled trial . Setting s East Hospital , Gothenburg , and 27 maternity care centres in Sweden . Participants 386 pregnant women with pelvic girdle pain . Interventions Treatment for six weeks with st and ard treatment ( n = 130 ) , st and ard treatment plus acupuncture ( n = 125 ) , or st and ard treatment plus stabilising exercises ( n = 131 ) . Main outcome measures Primary outcome measure was pain ( visual analogue scale ) ; secondary outcome measure was assessment of severity of pelvic girdle pain by an independent examiner before and after treatment . Results After treatment the stabilising exercise group had less pain than the st and ard group in the morning ( median difference = 9 , 95 % confidence interval 1.7 to 12.8 ; P = 0.0312 ) and in the evening ( 13 , 2.7 to 17.5 ; P = 0.0245 ) . The acupuncture group , in turn , had less pain in the evening than the stabilising exercise group ( −14 , −18.1 to −3.3 ; P = 0.0130 ) . Furthermore , the acupuncture group had less pain than the st and ard treatment group in the morning ( 12 , 5.9 to 17.3 ; P < 0.001 ) and in the evening ( 27 , 13.3 to 29.5 ; P < 0.001 ) . Attenuation of pelvic girdle pain as assessed by the independent examiner was greatest in the acupuncture group . Conclusion Acupuncture and stabilising exercises constitute efficient complements to st and ard treatment for the management of pelvic girdle pain during pregnancy . Acupuncture was superior to stabilising exercises in this study OBJECTIVE To investigate the efficacy of home-based specific stabilizing exercises focusing on the local stabilizing muscles as the only intervention in the treatment of persistent postpartum pelvic girdle pain . DESIGN A prospect i ve , r and omized , single-blinded , clinical ly controlled study . SUBJECTS Eighty-eight women with pelvic girdle pain were recruited 3 months after delivery . METHODS The treatment consisted of specific stabilizing exercises targeting the local trunk muscles . The reference group had a single telephone contact with a physiotherapist . Primary outcome was disability measured with Oswestry Disability Index . Secondary outcomes were pain , health-related quality of life ( EQ-5D ) , symptom satisfaction , and muscle function . RESULTS No significant differences between groups could be found at 3- or 6-month follow-up regarding primary outcome in disability . Within-group comparisons showed some improvement in both groups in terms of disability , pain , symptom satisfaction and muscle function compared with baseline , although the majority still experienced pelvic girdle pain . CONCLUSION Treatment with this home-training concept of specific stabilizing exercises targeting the local muscles was no more effective in improving consequences of persistent postpartum pelvic girdle pain than the clinical ly natural course . Regardless of whether treatment with specific stabilizing exercises was carried out , the majority of women still experienced some back pain almost one year after pregnancy PURPOSE Despite the high prevalence of back pain and its subsequent effects in post-partum women , intervention programs are scarce . The purpose of this study was to test the effects of a back-pain-reducing program on post-partum women who experienced low-back pain during pregnancy . METHODS A non-equivalent control-group pretest-posttest design was used . Pregnant women who attended a hospital for prenatal check-ups and experienced back pain participated in an intervention program ( n=27 ) , and the results were compared with women in a control group from another hospital ( n=25 ) . RESULTS At 8 weeks post-partum , the pain intensity , functional limitations were lower in the intervention group than in the control group . However , differences in mean change of the pain intensity and functional limitations between 36 and 39 weeks of gestation and at 8 weeks post-partum were not statistically significant between the groups . Moreover , the flexibility , post-partum functional status , and post-partum depression did not differ significantly between the groups . CONCLUSIONS A back-pain-relief program in this study was not effective to reduce the back-pain intensity in post-partum women and to decrease the associated functional limitations . The implication s for nursing practice and directions for future research are discussed Background . The study was design ed to evaluate the analgesic effect and possible adverse effects of acupuncture for pelvic and low‐back pain during the last trimester of pregnancy OBJECTIVE The purpose of this study was to describe the clinical outcomes of patients with pregnancy-related lumbopelvic pain ( PRLP ) treated according to a diagnosis-based clinical decision rule . METHODS This was a prospect i ve observational cohort of consecutive patients with PRLP . Data on 115 patients were collected at baseline and on 78 patients at the end of the active treatment . Disability was measured using the Bournemouth Disability Question naire ( BDQ ) . Pain intensity was measured using the Numerical Rating Scale for pain ( NRS ) . Patients were also asked to self-rate their improvement . Care was provided by a chiropractic physician/physical therapist team . RESULTS Fifty-seven patients ( 73 % ) reported their improvement as either " excellent " or " good . " The mean patient-rated improvement was 61.5 % . The mean improvement in BDQ was 17.8 points . The mean percentage of improvement in BDQ was 39 % and the median was 48 % . Mean improvement in pain was 2.9 points . Fifty-one percent of the patients had experienced clinical ly significant improvement in disability and 67 % patients had experienced clinical ly significant improvement in pain . Patients were seen an average 6.8 visits . Follow-up data for an average of 11 months after the end of treatment were collected on 61 patients . Upon follow-up , 85.5 % of patients rated their improvement as either " excellent " or " good . " The mean patient-rated improvement was 83.2 % . The mean improvement in BDQ was 28.1 points . The mean percentage of improvement in BDQ was 68 % and the median was 87.5 % . Mean improvement in pain was 3.5 points . Seventy-three percent of the patients had experienced clinical ly significant improvement in disability and 82 % patients had experienced clinical ly significant improvement in pain . CONCLUSIONS The management strategy used in this study appeared to yield favorable outcomes in this patient population and appears to be a safe option for patients with PRLP , although because of this study 's sample size , rare complications are not likely to be detected . In addition , the absence of r and omization and a control group limits interpretation with regard to clinical effectiveness . R and omized , controlled trials are necessary to distinguish treatment effects from the natural history of PRLP A single center , prospect i ve , r and omized , single blinded , controlled study comparing the effects and safety of " sitting pelvic tilt exercise " in relieving back pain during the third trimester in primigravida was carried out . The sample s were composed of 67 primigravidas who attended the prenatal clinic at King Chulalongkorn Memorial Hospital . All subjects were selected by the r and om sampling technique and allocated into two groups for the experimental group and the control group ; for 32 and 35 pregnants , respectively . The experimental group received the pelvic tilt exercise program for 8 weeks during the third trimester . Pain intensity was measured by visual analogue scale ( VAS ) at day 0 and day 56 in both groups . The result of the study revealed 1 ) The mean VAS of back pain in the experimental group was significantly lower at day 56 than at day 0 and lower than the control group at day 56 ( p < 0.05 ) by unpaired t-test 2 ) There was no incidence of preterm labor , low birth weight or neonatal complication in the experimental group . In conclusion , the " sitting pelvic tilt exercise " during the third trimester in primigravidas could decrease back pain intensity without incidence of preterm labor , low birth weight or neonatal complication Study Design . In this prospect i ve , consecutive , controlled cohort study , the authors analyzed the impact of a differentiated , individual‐based treatment program on sick leave during pregnancy for women experiencing lumbar back or posterior pelvic pain during pregnancy . Objective . To identify patients with pain early in pregnancy and , by means of individual information and differentiated physiotherapy , reduce sick leave during pregnancy . Summary of Background Data . Sick leave for back pain during pregnancy is common , and treatment programs have been aim ed at reducing pain , for that reason . In Sweden , the average sick leave due to back pain during pregnancy is 7 weeks . Methods . All pregnant women who attended a specific antenatal clinic and experienced lumbar back or posterior pelvic pain were included in an intervention group , and results were compared with women in a control group from another antenatal clinic . Results . The intervention group comprised 54 women , compared with 81 women in the control group . Thirty‐three women were on sick leave for an average of 30 days in the intervention group versus 45 women for an average of 54 days in the control group ( P < 0.001 ) . The reduction in sick leave reduced insurance costs by approximately $ 53,000 U.S. Conclusions . Sick leave for lumbar back and posterior pelvic pain in the intervention group was significantly reduced with the program , and the program was cost effective Abstract . This study is a prospect i ve , consecutive , 3-year cohort study of women with back pain in an index pregnancy . The aim was to describe the physical status and disability among women with back pain 3 years after delivery . Pain was identified as lumbar back pain , posterior pelvic pain or combined lumbar as well as posterior pelvic pain . Previous studies have established that all three types of pain can be reduced by structured physiotherapy during pregnancy , and the beneficial effect may last for several years . Though it is known that some women have residual pain for a long time , the relative incidence of the three pain types and their degree of disability associated with each have never been reported . Neither has any study presented findings of a physical examination of women 3 years post partum with a focus on the type of pain . All women who were registered as having experienced back pain during an index pregnancy were interviewed by mail 3 years post partum . Women who had residual back pain filled in an additional question naire and were physically examined . Out of 799 pregnant women , 231 had some type of back pain during the index pregnancy , and 41 women had pain 3 years later . Women with combined lumbar and posterior pelvic pain were significantly more disabled ( P<0.05 ) and had significantly lower endurance in the lumbar back and hip abduction muscles ( P<0.01 ) . Some 5 % of all pregnant women , or 20 % of all women with back pain during pregnancy , had pain 3 years later . The key problem may be poor muscle function in the back and pelvis Background Many women have low back pain ( LBP ) or pelvic girdle pain ( PGP ) during pregnancy , but there is limited evidence of effective primary and secondary preventive strategies . Objective The purpose of this study was to investigate whether a group-based exercise program can reduce the prevalence and severity of LBP and PGP in pregnant women . Design An observer-blinded r and omized controlled trial with equal assignments to a training group and a control group was conducted . Setting The study was conducted in primary care maternity units in 2 suburban municipalities in the southeastern part of Norway . Patients The participants were 257 pregnant women who were healthy and between 18 and 40 years of age before gestation week 20 . Intervention The training group received supervised exercises in groups once a week , and the control group received st and ard care . Measurements The main outcome measures were self-reported LBP and self-reported PGP . Secondary outcome measures were pain intensity in the morning and evening , disability , and 8-Item Short-Form Health Survey ( SF-8 ) Physical Component Summary ( PCS ) and Mental Component Summary ( MCS ) scores . Follow-up measurements were performed at gestation weeks 24 , 28 , 32 , and 36 . Results Overall , there was no effect of the program on the prevalence of PGP ( odds ratio=1.03 , 95 % confidence interval [CI]=0.66 to 1.59 ) or LBP ( odds ratio=0.77 , 95 % CI=0.50 to 1.19 ) . For the secondary outcomes , the estimated mean differences between the groups were −0.4 ( 95 % CI=−0.8 to 0.1 ) for pain intensity in the morning , −0.4 ( 95 % CI=−1.0 to 0.2 ) for pain intensity in the evening , −1.0 ( 95 % CI=−2.2 to 0.0 ) for disability , 1.8 ( 95 % CI=0.0 to 3.7 ) for the SF-8 PCS , and −0.6 ( 95 % CI=−2.2 to 1.4 ) for the SF-8 MCS . Limitations Due to low statistical power , the estimates for the primary outcomes are imprecise . Conclusions Supervised group exercise did not reduce the prevalence of LBP or PGP in pregnancy Study Design . A r and omized controlled trial with stratified block design . Objectives . To evaluate a treatment program focusing on whether specific stabilizing exercises for patients with pelvic girdle pain after pregnancy reduce pain , improve functional status , and improve quality of life . Summary of Background Data . The evidence of effectiveness of treatment for pelvic girdle pain is weak . Recent research has focused on the importance of activation of muscles for motor control and stability of the lumbopelvic region . To the authors ’ knowledge , the efficacy of applying these principles for pelvic girdle pain has not previously been evaluated in a r and omized controlled trial . Methods . Eighty-one women with pelvic girdle pain were assigned r and omly to two treatment groups for 20 weeks . One group received physical therapy with a focus on specific stabilizing exercises . The other group received individualized physical therapy without specific stabilizing exercises . Assessment s were administered by a blinded assessor , at baseline , after intervention and 1 year post partum . Main outcome measures were pain , functional status and quality of life . Results . There were no dropouts . After intervention and at 1 year post partum , the specific stabilizing exercise group showed statistically and clinical ly significant lower pain intensity , lower disability , and higher quality of life compared with the control group . Group difference in median values for evening pain after treatment was 30 mm on the Visual Analog Scale . Disability was reduced by more than 50 % for the exercise group ; changes were negligible in the control group . Significant differences were also observed for physical tests , in favor of the specific exercise group . Conclusion . An individualized treatment approach with specific stabilizing exercises appears to be more effective than physical therapy without specific stabilizing exercises for women with pelvic girdle pain after pregnancy BACKGROUND AND PURPOSE Symphysis pubis pain is a significant problem for some pregnant women . The purpose of this study was to investigate the effects of exercise , advice , and pelvic support belts on the management of symphysis pubis dysfunction during pregnancy . SUBJECTS Ninety pregnant women with symphysis pubis dysfunction were r and omly assigned to 3 treatment groups . METHODS A r and omized masked prospect i ve experimental clinical trial was conducted . Specific muscle strengthening exercises and advice concerning appropriate methods for performing activities of daily living were given to the 3 groups , and 2 of the groups were given either a rigid pelvic support belt or a nonrigid pelvic support belt . The dependent variables , which were measured before and after the intervention , were a Rol and -Morris Question naire score , a Patient-Specific Functional Scale score , and a pain score ( 101-point numerical rating score ) . RESULTS After the intervention , there was a significant reduction in the Rol and -Morris Question naire score , the Patient-Specific Functional Scale score , and the average and worst pain scores in all groups . With the exception of average pain , there were no significant differences between groups for the other measures . DISCUSSION AND CONCLUSION The findings indicate that the use of either a rigid or a nonrigid pelvic support belt did not add to the effects provided by exercise and advice OBJECTIVE The primary aim of this study was to examine whether 1 week of continuous auricular acupuncture could reduce low back and posterior pelvic pain associated with pregnancy . STUDY DESIGN A r and omized controlled trial was conducted on pregnant women who have lower back and posterior pelvic pain . These women were r and omly assigned into an acupuncture group , a sham acupuncture group , or a waiting list control group . All participants were monitored for 2 weeks . RESULTS Baseline and day 7 showed significant group differences in pain ( F = 15 ; P < .0001 ) and in the disability rating index score ( F = 7 ; P < .0001 ) . The participants in the acupuncture group reported a significant reduction of pain and improvement of functional status as compared with those in the sham acupuncture and control groups . CONCLUSION One week of continuous auricular acupuncture decreases the pain and disability experienced by women with pregnancy-related low back and posterior pelvic pain Background . Prevention of lumbopelvic pain in pregnancy has been sparsely studied . One aim of this study was to assess if a 12‐week training program during pregnancy can prevent and /or treat lumbopelvic pain . A r and omized controlled trial was conducted at Trondheim University Hospital and three outpatient physiotherapy clinics . Three hundred and one healthy nulliparous women were included at 20 weeks of pregnancy and r and omly allocated to a training group ( 148 ) or a control group ( 153 ) . Methods . The outcome measures were self‐reported symptoms of lumbopelvic pain ( once per week or more ) , sick leave , and functional status . Pain drawing was used to document the painful area of the body . The intervention included daily pelvic floor muscle training at home , and weekly group training over 12 weeks including aerobic exercises , pelvic floor muscle and additional exercises , and information related to pregnancy . Results . At 36 weeks of gestation women in the training group were significantly less likely to report lumbopelvic pain : 65/148 ( 44 % ) versus 86/153 ( 56 % ) ( p = 0.03 ) . Three months after delivery the difference was 39/148 ( 26 % ) in the training group versus 56/153 ( 37 % ) in the control group ( p = 0.06 ) . There was no difference in sick leave during pregnancy , but women in the training group had significantly ( p = 0.01 ) higher scores on functional status . Conclusions . A 12‐week specially design ed training program during pregnancy was effective in preventing lumbopelvic pain in pregnancy BACKGROUND most pregnant women experience back pain during pregnancy , a serious issue that negatively impacts life quality during pregnancy . Research into an exercise intervention programme targeting low back pain and daily life interference is lacking . OBJECTIVE this study evaluates how a stability ball exercise programme influences low back pain and daily life interference across the second and third pregnancy trimester . METHODS the study was non-r and omised and controlled , examining a target population of low-risk pregnancy women between 20 and 22 weeks of gestation located in a regional hospital in northern Taiwan . All participants had at least minimal low back pain , no prior history of chronic low back pain before pregnancy , and no indications of preterm labour . In total , 89 individuals participated : 45 in the control group and 44 in the experimental group ( who attended an antenatal stability ball exercise programme ) . This programme lasted 12 weeks , composed of at least three sessions per week . Fitness workouts lasted from 25 to 30 minutes . The women completed their basic personal information , the Brief Pain Inventory-Short Form , and the Family Exercise Support Attitude Question naire . RESULTS after adjusting for demographic data and antenatal exercise status by propensity scores , experimental-group women who participated in the antenatal stability ball exercise programme reported significantly less low back pain and daily life interferences than the control group at 36 weeks of gestation . DISCUSSION the inclusion of stability ball exercises during pregnancy may reduce pregnancy low back pain and boost daily life functions . This stability ball exercise programme provides health-care professionals with an evidence -based intervention INTRODUCTION Back pain is commonly experienced by pregnant women . Evidence suggests that progressive muscle relaxation ( PMR ) therapy , a complementary therapy widely used by pregnant women , may improve the physical and psychological outcomes of pregnancy . The aim of this study was to investigate the effects of PMR training accompanied by music on perceived pain and quality of life ( QOL ) in pregnant women with low back pain ( LBP ) . METHODS This was a prospect i ve r and omized controlled trial . The study was design ed to examine the effects of PMR accompanied by music on pregnant women with LBP . In total , 66 pregnant women were assigned r and omly to a PMR group or a control group ( 33 women in each ) . A personal information form was used as a data collection tool ; a visual analog scale was used for measuring pain ; and the Short Form-36 was used to evaluate QOL . RESULTS The control and intervention groups were comparable at baseline . Significant differences were observed between the 2 groups after 4 and 8 weeks of intervention . The intervention group showed significant improvement in all QOL subscales after the intervention . The intervention group , but not the control group , showed significant improvement in perceived pain after the intervention . The intervention group experienced a greater decrease in perceived pain and improved QOL than the control group . DISCUSSION Our findings show that PMR accompanied by music may be an effective therapy for improving pain and QOL in pregnant women with LBP . Large r and omized studies are recommended to confirm these results Study Design This study analyzed an education and training program concerning back and pelvic problems among pregnant women . Objective The program was aim ed at reducing tack and pelvic posterior pain during pregnancy . Summary of Background Data Low back and posterior pelvic pain accounts for the majority of sick leave among pregnant women . No previous study has suggested any type of solution to this problem . Methods Four hundred and seven consecutive pregnant women were included in the study and r and omly assigned into three groups . Group A served as controls while different degrees of interventions were made in groups B and C. Results Serious back or posterior pelvic pain developed in 47 % of all women . Pain-related problems were reduced in groups B and C ( P < 0.05 ) , and sick-leave frequency was reduced in group C ( P < 0.01 ) . For some of the women in this group pain intensity was also reduced 8 weeks post partum ( P < 0.005 ) . Weekly physical exercise before pregnancy reduced the risk for back pain problems in pregnancy ( P < 0.05 ) . A non-elastic sacro-illac belt offered some pain relief to 82 % of the women with posterior pelvic pain . Conclusions An individually design ed program reduced sick leave during pregnancy . Working with groups was less effective . Differentiation between low back and posterior pelvic pain was essential . Good physical fitness reduced the risk of back pain in a subsequent pregnency . Reduction of posterior pelvic pain by a non-elastic pelvic support was experienced by 82 % of the women with posterior pelvic pain BACKGROUND AND PURPOSE Exercises for low back and pelvic pain are supposed to increase muscle force to reduce symptoms , but they could exacerbate symptoms by loading of the spinal and pelvic structures . The purpose of this study was to investigate the value of grade d exercises of the diagonal trunk muscle systems . SUBJECTS The subjects were 44 women with persistent pelvic pain after pregnancy ( mean age=31.7 years , SD=3.2 , range=23.6 - 37.5 ; mean period postpartum=4.1 months , SD=2.2 , range=1.7 - 5.6 ) . METHODS Subjects were r and omly assigned to 1 of 3 groups : ( 1 ) a group that performed exercises to increase the force of the diagonal trunk muscle systems , ( 2 ) a group that received training of the longitudinal trunk muscle systems , and ( 3 ) a group that was instructed to refrain from exercises . Pain , fatigue , perceived general health , and mobility of the pelvic joints as measured with radiographs were the outcome measures . RESULTS After 8 weeks , no differences were found among the 3 groups . CONCLUSION AND DISCUSSION In treating patients with persistent pelvic pain , training of the diagonal trunk muscle systems , without individual coaching , has no additional value above instructions and use of a pelvic belt without exercises . Whether the treatment is ineffective or whether exacerbation of symptoms due to loading of the spinal and pelvic structures obscures any potential benefit of increased muscle force can not be determined from the study design Objective . An earlier publication showed that acupuncture and stabilising exercises as an adjunct to st and ard treatment was effective for pelvic girdle pain during pregnancy , but the post‐pregnancy effects of these treatment modalities are unknown . The aim of this follow‐up study was to describe regression of pelvic girdle pain after delivery in these women . Design . A r and omised , single blind , controlled trial . Setting . East Hospital and 27 maternity care centres in Göteborg , Sweden . Population . Some 386 pregnant women with pelvic girdle pain . Methods . Participants were r and omly assigned to st and ard treatment plus acupuncture ( n = 125 ) , st and ard treatment plus specific stabilising exercises ( n = 131 ) or to st and ard treatment alone ( n = 130 ) . Main outcome measures . Primary outcome measures : pain intensity ( Visual Analogue Scale ) . Secondary outcome measure : assessment of the severity of pelvic girdle pain by an independent examiner 12 weeks after delivery . Results . Approximately three‐quarters of all the women were free of pain 3 weeks after delivery . There were no differences in recovery between the 3 treatment groups . According to the detailed physical examination , pelvic girdle pain had resolved in 99 % of the women 12 weeks after delivery . Conclusions . This study shows that irrespective of treatment modality , regression of pelvic girdle pain occurs in the great majority of women within 12 weeks after delivery Study Design A prospect i ve , consecutive cohort analysis of the regression of the incidence and intensity of back and posterior pelvic pain after delivery in pregnant women was done . Objective To identify back and posterior pelvic pain from mid‐pregnancy to 5 months after delivery and to illustrate differences between these two pain types . Summary of Background Data Chronic back pain may start during a pregnancy , and regression of unspecified back pain after delivery may be slow and incomplete . Few studies have distinguished back pain from posterior pelvic pain in pregnancy , and no study has presented follow‐up data after delivery with respect to pain types . Methods One hundred and sixty four of 368 pregnant women studied had back or posterior pelvic pain and were offered individual group physiotherapy and training . The women were observed until 5 months after delivery . St and ardized clinical examination protocol s and question naires were used . Results Posterior pelvic pain was experienced by 124 women , and back pain was experienced by 40 women during pregnancy . After delivery , however , back pain was more common . Pain intensity was higher among women with posterior pelvic pain during pregnancy , whereas after delivery pain intensity was higher among women with back pain . A correlation was found between the presence of high pain intensity during pregnancy and little regression of pain after delivery . Conclusions One of every three pregnant women studied experienced posterior pelvic pain , and one of every nine women experienced back pain . Posterior pelvic pain was more intense during pregnancy , and back pain was more intense and more common after delivery . High pain intensity in pregnancy indicated a bad prognosis BACKGROUND Although many pregnant women experience back pain , it has not considered an important health problem . No study has investigated the effects of a back-pain-reducing program ( BPRP ) during pregnancy for Korean women . OBJECTIVE The purpose of this study was to evaluate the effect of a program design ed to reduce back pain in pregnant women . METHODS A non-equivalent control-group pretest-posttest design was used . Pregnant women who attended an antenatal clinic and experienced back pain during their pregnancy were included in an intervention group ( n=29 ) , and their intensity of back pain , functional limitation and anxiety were compared with women in a control group from another antenatal clinic ( n=27 ) . The data were collected at three time points : prior to intervention , and 6 and 12 weeks after intervention . RESULTS At 12 weeks after intervention , the intensity of back pain experienced by the intervention group was significantly lower than that of the control group . However , there were no statistically significant differences between the groups with respect to functional limitations and anxiety . CONCLUSIONS The findings show that the pain-reducing program developed for this study was effective in reducing the intensity of back pain experienced by pregnant women . Promoting good posture and regular exercise can be recommended as a method to relieve back pain in pregnancy women . Further studies are needed to confirm the effect of the BPRP during pregnancy OBJECTIVE To compare the effect of a l and -based , physical exercise program versus water aerobics on low back or pelvic pain and sick leave during pregnancy . DESIGN R and omized controlled clinical trial . SETTING Three antenatal care centers . PARTICIPANTS 390 healthy pregnant women . INTERVENTIONS A l and -based physical exercise program or water aerobic once a week during pregnancy . MAIN OUTCOME MEASURES Sick leave , pregnancy-related low back pain or pregnancy-related pelvic girdle pain , or both . RESULTS Water aerobics diminished pregnancy-related low back pain ( p=.04 ) and sick leave due to pregnancy-related low back pain ( p=.03 ) more than a l and -based physical exercise program . CONCLUSIONS Water aerobics can be recommended for the treatment of low back pain during pregnancy . The benefits of a l and -based physical exercise program are question able and further evaluation is needed Adverse and analgesic effects of acupuncture during the second and third trimesters of pregnancy were studied retrospectively in an observational study including 167 consecutive patients with lower back pain , pelvic pain , or both . In each patient acupuncture was given on at least two different occasions by three manual stimulations of two or more acupuncture or tender points , mainly LR-3 and LI-4 together with local tender points , at 15-min intervals . Possible adverse and analgesic effects were assessed by the midwife responsible for the acupuncture given in each patient . There were no abortions and no influence on the delivery course of the infants , but transient premature labor was observed during the fourth stimulation carried out in the 15th gestational week in one woman . Other possible adverse effects , like transient dizziness or tiredness , were reported in 35 patients ( 21 % ) . Analgesia , as assessed by midwives involved , was good or excellent in 72 % of patients . Acupuncture seems to be safe and effective for pain relief in lower back pain , pelvic pain , or both during the second and third trimesters of pregnancy . Nevertheless , prospect i ve r and omized studies are needed to confirm these findings Study Design . A r and omized assessor-blinded clinical trial was conducted . Objective . To compare 3 different physical therapy treatments with respect to pain and activity in women with pelvic girdle pain during pregnancy and 3 , 6 , and 12 months postpartum . Summary of Background Data . In spite of the high prevalence of back pain during pregnancy , documented treatment programs are limited . Methods . Based on a clinical examination , 118 women with pelvic girdle pain diagnosed during pregnancy were r and omized into 3 different treatment groups : Information Group , use of a nonelastic sacroiliac belt and oral/written information about pelvic girdle pain ( n = 40 ) ; Home Exercise Group , same as in the Information Group , with the addition of a home exercise program ( n = 41 ) ; and the In Clinic Exercise Group , same as in the Information Group , plus participation in a training program ( n = 37 ) . Pain intensity was rated on a visual analogue scale ( 0–100 mm ) and marked on a pain drawing concerning localization . The activity ability was scored using the Disability Rating Index , covering 12 daily activity items . Outcome measures were obtained at inclusion , on average in gestation week 38 , and 3 , 6 , and 12 months postpartum . Results . There was no significant difference among the 3 groups during pregnancy or at the follow-ups postpartum regarding pain and activity . In all groups , pain decreased and the activity ability increased between gestation week 38 and at 12 months postpartum . Conclusions . Women with pelvic girdle pain seemed to improve with time in all 3 treatment groups . Neitherhome nor in clinic exercises had any additional value above giving a nonelastic sacroiliac belt and information Study Design A longitudinal , prospect i ve , observational , cohort study . Objectives To describe the natural history of back pain occurring during pregnancy and immediately after delivery . Summary of Background Data Back pain during pregnancy is a frequent clinical problem even during the early stages of pregnancy . The cause is unclear . Methods A cohort of 200 consecutive women attending an antenatal clinic were followed throughout pregnancy with repeated measurements of back pain and possible determinants by question naires and physical examinations . Results Seventy‐six percent reported back pain at some time during pregnancy . Sixty‐one percent reported onset during the present pregnancy . In this group , the prevalence rate increased to 48 % until the 24th week and then remained stable and declined to 9.4 % after delivery . The reported pain intensity increased by pain duration . The pain score correlated closely to self‐rated disability and days of sickness benefit . Conclusions Back pain during pregnancy is a common complaint . The 30 % with the highest pain score reported great difficulties with normal activities . The back pain started early in pregnancy and increased over time . Young women had more pain than older women . Back pain starting during pregnancy may be a special entity and may have another origin than back pain not related to pregnancy Background No appropriate measures have been specifically developed for pelvic girdle pain ( PGP ) . There is a need for suitable outcome measures that are reliable and valid for people with PGP for use in research and clinical practice . Objective The objective of this study was to develop a condition-specific measure , the Pelvic Girdle Question naire ( PGQ ) , for use during pregnancy and postpartum . Design This was a methodology study . Methods Items were developed from a literature review and information from a focus group of people who consulted physical therapists for PGP . Face validity and content validity were assessed by classifying the items according to the World Health Organization 's International Classification of Functioning , Disability and Health . After a pilot study , the PGQ was administered to participants with clinical ly verified PGP by means of a postal question naire in 2 surveys . The first survey included 94 participants ( 52 pregnant ) , and the second survey included 87 participants ( 43 pregnant ) . Rasch analysis was used for item reduction , and the PGQ was assessed for unidimensionality , item fit , redundancy , and differential item functioning . Test-retest reliability was assessed with a r and om sample of 42 participants . Results The analysis result ed in a question naire consisting of 20 activity items and 5 symptom items on a 4-point response scale . The items in both subscales showed a good fit to the Rasch model , with acceptable internal consistency , satisfactory fit residuals , and no disordered threshold . Test-retest reliability showed high intraclass correlation coefficient estimates : .93 ( 95 % confidence interval=0.86–0.96 ) for the PGQ activity subscale and .91 ( 95 % confidence interval=0.84–0.95 ) for the PGQ symptom subscale . Limitations The PGQ should be compared with low back pain question naires as part of a concurrent evaluation of measurement properties , including validity and responsiveness to change . Conclusions The PGQ is the first condition-specific measure developed for people with PGP . The PGQ had acceptably high reliability and validity in people with PGP both during pregnancy and postpartum , it is simple to administer , and it is feasible for use in clinical practice OBJECTIVE To examine the feasibility , acceptability , and effectiveness of a support binder for low back pain in pregnancy . DESIGN Pilot study , using a prospect i ve , two-group design with repeated measures . SETTING Ambulatory maternity clinic in a tertiary care teaching hospital . PARTICIPANTS Women of at least 20 weeks gestation with low back pain , but no preexisting back or disc disease . Thirty women assigned to the intervention group and 10 to a comparison group . INTERVENTIONS Participants completed a pain assessment at pretest . Intervention participants received a maternity support binder to wear while awake for 2 weeks . At an appointment 2 weeks later , a posttest question naire and a taped interview were administered . The comparison group participants received the support binder after the second appointment . MAIN OUTCOME MEASURES Back pain intensity , duration , and effect on daily activities were assessed using a pain in pregnancy question naire . RESULTS The intervention group had significant reduction in mean pain scores and effect of pain on daily activities , including family , house and yard , recreational , exercise , and sleep . Interaction of group by time was significant for change in pain and effect on family , house and yard , and exercise activities . CONCLUSION The use of a support binder for pregnancy-related low back pain is a promising intervention and was well-accepted by the participants Background . The aim of this study was to describe the effects of acupuncture in the treatment of low‐back and pelvic pain during pregnancy and compare it with physiotherapy Background . The efficacy of acupuncture on low‐back and /or pelvic pain in late pregnancy is review ed in few reports . Our aim was to evaluate the effects of two different acupuncture stimulation modes on pelvic pain intensity and some emotional symptoms due to the pain condition . Methods . In a prospect i ve r and omized controlled single‐blind study , pregnant women with pelvic pain , median gestational age 26 weeks ( range 18–35 ) , were given 10 acupuncture treatments . Needles were inserted subcutaneously over acupuncture points without further stimulation ( superficial , n=22 ) , or intramuscular and stimulated repeatedly until a perceived sensation of numbness , de qi , ( deep , n=25 ) . Self‐reported pain intensity at rest and during daily activities was assessed on a visual analog scale . The variables pain , emotional reactions , and loss of energy were assessed according to the Nottingham Health Profile question naire . Changes in assessed variables were analyzed with a nonparametric statistical method allowing for analysis of systematic group changes separated from additional individual changes . Results . After acupuncture stimulation , significant systematic group changes towards lower levels of pain intensity at rest and in daily activities as well as in rated emotional reaction and loss of energy were seen . The results also showed additional individual changes in most variables . In this study , no differences between the effects induced by the superficial and deep acupuncture stimulation modes were observed . Conclusion . Acupuncture stimulation that is individually design ed may be a valuable treatment to ameliorate suffering in the condition of pelvic pain in late pregnancy |
13,584 | 15,179,561 | Based on the currently best available evidence it appears that most patients with masticatory muscle pain are helped by the incorporation of a stabilization splint .
Nevertheless , evidence is equivocal if improvement of pain symptoms after incorporation of the intraoral appliance is caused by a specific effect of the appliance .
A stabilization splint does not appear to yield a better clinical outcome than a soft splint , a non-occluding palatal splint , physical therapy , or body acupuncture . | This study aim ed at providing an answer to two clinical questions related to patients with masticatory muscle pain : 1 ) Does the use of a full-coverage hard acrylic occlusal appliance ( stabilization splint ) lead to a significant decrease of symptoms ?
and 2 ) Is the treatment success achieved with a stabilization splint more pronounced than the success attained with other forms of treatment ( including placebo treatment ) or no treatment ? | The aim of the present study was to compare the effect of transcutaneous electric nerve stimulation ( TENS ) with the flat occlusal splint in the treatment of temporom and ibular joint ( TMJ ) disk displacement without reduction . Thirty-one patients were included and r and omly selected to be treated 6 weeks with either TENS ( 90 Hz , 30 min , three times/day ) or with a flat occlusal splint ( 24 h/day . Those selected for the TENS group had one electrode placed over the painful TMJ and another electrode over the anterior temporal muscle . The splint group used a conventional flat occlusal splint with cuspid guidance . Both treatment groups visited the clinic once a week . Symptoms and signs were registered before and after treatment . The intensity of pain was recorded with a visual analogue scale ( VAS ) and with an electronic pocket-sized recorder ( Pain-Track ) carried 1 week before and also the last week of treatment for continuous registration of pain . Measured with the VAS , half of the patients treated with splints became pain-free or their TMJ pain improved at least 50 % both at rest and with jaw function compared with only 6 % in the TENS-treated group . With regard to strictly chewing pain , the VAS-registered pain improved in two-thirds of the splint group , compared with 50 % of the TENS group . With the Pain-Track device it was found that in most individuals pain was aggrevated at mealtimes . The conclusion was that flat occlusal splints in several respects are better than TENS in the treatment of symptoms associated with TMJ disk displacement without reduction Masticatory myofascial pain ( MFP ) condition is a musculoskeletal disorder that compromises the functional capacities of the masticatory system . As such , the incorporation of an intensive chewing test as a discriminatory exercise for the diagnosis of this condition and evaluation of treatment success has considerable potential . Various splint design s have been used successfully , which have posed a question of whether the therapeutic effect of the splint is a placebo or has some other curative properties . The purpose of this study was to evaluate the efficacy of the stabilization appliance to reduce signs and symptoms in MFP patients and to compare the pain experience during the chewing test between two groups of patients , with and without splints . Myofascial pain patients ( n = 37 ) who reported exacerbation of pain in function participated in the study . Patients perfomed a 9-min chewing test , followed by 9-min rest and marked their pain intensity on a visual analogue scale every 3 min . Of the 37 patients , 21 received a stabilization flat occlusal splint for night use and 16 were equally monitored clinical ly without a splint . At the end of 8 weeks , a second clinical examination and chewing test were performed . Student 's t-test was used to analyse differences between study groups . Analysis of variance and covariance ( ancova ) with repeated measures was applied to analyse the effect of treatment . Level of pain at baseline prior to the chewing test ( P0 ) was introduced as a co-variant . At baseline both groups showed relatively high scores of pain intensity and did not show any significant differences among the collected variables . At the end of the experiment , the splint group had a statistically significant reduction in pain intensity , in mean muscle sensitivity to palpation and in the pain experience during the chewing test compared with no change in the controls . A stabilization splint has a therapeutic value beyond its placebo effects . Thus , it should be an integral part of the treatment modalities in MFP disorder patients . An intensive chewing test is an effective tool to evaluate the treatment modality efficacy in MFP patients AIMS To compare the short-term efficacy of treatment with a stabilization appliance compared with that of a non-occlusal , control appliance in patients with temporom and ibular disorders ( TMD ) of mainly myogenous origin . METHODS A r and omized , controlled trial was performed with 60 patients suffering from myofascial pain . Patients were r and omly assigned to a treatment or a control group . The treatment group was treated by means of a stabilization appliance and the control group by means of a non-occlusal appliance . Symptoms and signs were registered before and after 10 weeks of treatment . RESULTS Improvement of overall subjective symptoms was reported in both groups , but significantly more often in the treatment group than in the control group ( P = .000 ) . The prevalence of daily or constant pain showed a significant reduction in the treatment group ( P = .028 ) compared with the control group . There was a significant decrease in the number of tender masticatory muscles in the treatment group ( P = .018 ) compared with the control group . CONCLUSION The results of this short-term evaluation suggest that the stabilization appliance is more effective in alleviating symptoms and signs in patients with TMD of mainly myogenous origin than a control , non-occlusal appliance . The stabilization appliance can therefore be recommended for the therapy of these patients 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 In order to evaluate and compare the effects of biofeedback and occlusal splint therapy on m and ibular dysfunction , 30 patients were r and omly divided into two treatment groups . The patients were women aged 20 - -40 years without any obvious organic reasons for their symptoms . There were no significant differences between the two groups before the start of treatment in respect of signs and symptoms of m and ibular dysfunction . One group used full coverage splints at night for 6 weeks . The other group received biofeedback training up to six times , 30 min per session . One month after completion of the therapy the patients were re-examined . Both groups showed a significant reduction in symptoms , both subjectively and clinical ly . No significant differences between the groups were found . The two treatments were thus equally effective in the short-term perspective in patients with signs and symptoms of m and ibular dysfunction Forty-five individuals with long-st and ing facial pain or headache of muscular origin were r and omly allocated into three groups . The first group was treated with acupuncture , the second group received an occlusal splint , and the third group served as controls . Both acupuncture and occlusal splint therapy significantly reduced subjective symptoms and clinical signs from the stomatognathic system . No differences between these two groups were found with regard to treatment effects . It is concluded that acupuncture is an alternative method to conventional stomatognathic treatment for individuals with craniom and ibular disorders of muscular origin Twenty-four patients were selected to participate in this study . Twelve patients were r and omly selected to receive occlusal splint therapy and the other 12 to receive a simplified relaxation therapy technique . Observable pain scores , maximum comfortable interincisal distance , and maximum interincisal distances were recorded for each group before and after treatment . The occlusal splint group showed a significant decrease in total mean observable pain scores ( decrease score of 10.5 , t = 3.124 ; P less than 0.1 ) . The relaxation group showed no significant decrease in total mean observable pain scores ( decrease score of 1.8 , t = 0.888 ; P = ns ) . The occlusal splint group showed a significant increase in the mean maximum comfortable opening ( an increase of 12.4 mm , t = 5.085 ; P less than .01 ) . The relaxation group showed no significant increase in the mean maximum comfortable opening ( an increase of 2.3 mm , t = 0.734 ; P = ns ) . The occlusal splint group showed a significant increase in the mean maximum opening ( an increase of 6.0 mm , t = 2.471 ; P less than .05 ) . The relaxation group showed no increase in the mean maximum opening ( decrease of 0.7 mm , t = 0.343 ; P = ns ) . This study suggests that occlusal splint therapy is a more effective treatment for the pain , tenderness , and limited m and ibular opening associated with temporom and ibular disorders than relaxation therapy . In this study , the relaxation technique used had no significant effect on the patients ' pain , tenderness , or limited opening To assess the differential efficacy of two commonly used treatments for temporom and ibular disorders ( TMD ) , intraoral appliances ( IAs ) and biofeedback ( BF ) , separately and in combination , two studies were conducted . The first study directly compared IA treatment , a combination of biofeedback and stress management ( BF/SM ) , and a waiting list control group in a sample of 80 TMD patients . Both treatments were determined to be equally credible to patients , ruling out this potential threat to the validity of the results obtained . The results demonstrated that the IA treatment was more effective than the BF/SM treatment in reducing pain after treatment , but at a 6-month follow-up the IA group significantly relapsed , especially in depression , whereas the BF/SM maintained improvements on both pain and depression and continued to improve . The second study examined the combination of IA and BF/SM in a sample of 30 TMD patients . The results of this study demonstrated that the combined treatment approach was more effective than either of the single treatments alone , particularly in pain reduction , at the 6-month follow-up . These results support the importance of using both dental and psychologic treatments to successfully treat TMD patients if treatment gains are to be maintained The aim of this study was to investigate if the difference in treatment outcome between patients provided with a stabilisation appliance and a control appliance was due to the treatment and /or other factors in patients with temporom and ibular disorders ( TMD ) of arthrogeneous origin . Sixty patients were assigned to two equally sized groups : a treatment group , treated with a stabilisation appliance , and a control group given a control appliance . Thirteen possible background variables for the treatment outcome were correlated to changes in severity of temporom and ibular joint ( TMJ ) pain on a verbal scale in the two patient groups . The logistic regression analyses revealed that , after correcting for the background variables , stabilisation appliance treatment was a strong explanatory factor for a positive treatment outcome , with a significance of P = 0.0013 compared to patients belonging to the control group . Background variables of significant importance for the treatment outcome were male sex ( positive ) ( P = 0.0268 ) , and severe or very severe TMJ pain ( negative ) ( P = 0.0034 ) . These findings indicate that not only the treatment with a stabilisation appliance but also sex and the intensity of the TMJ pain before treatment might influence the treatment outcome in patients with TMD of arthrogeneous origin One hundred and ten patients , 23 males and 87 females , participated in a comparative study of the effect of acupuncture and occlusal splint therapy . All the patients exhibited signs and symptoms of craniom and ibular disorders ( CMD ) and had had pain for more than six months . The participants were r and omly assigned to three groups ; acupuncture treatment , occlusal splint therapy or control . The patients were evaluated before and immediately after treatment/control time . Ten different subjective and /or clinical assessment variables were used in the evaluation of the treatment effects . Both acupuncture and occlusal splint therapy reduced the symptoms as compared with the control group in which the symptoms remained essentially unchanged . In this short-term study , acupuncture gave better subjective results ( p < 0.001 ) than the occlusal splint therapy In a r and omized trial the effects of occlusal appliance and relaxation therapy , each combined with brief information , were compared with brief information only , in adolescents with temporom and ibular disorder ( TMD ) pain . One-hundred- and -twenty-two adolescents ( 93 F and 29 M aged 12 - 18 years ) were r and omly assigned to one of the following 3 groups : brief information + occlusal appliance ( BI + OA ) , brief information + relaxation therapy ( BI + RT ) , or brief information ( BI ) . Included were subjects reporting pain once a week or more often , in addition to receiving a diagnosis of TMD according to the Research Diagnostic Criteria ( RDC/TMD ) . They were evaluated before and after treatment and at a 6-month follow-up by means of self-reports and clinical assessment . The result revealed a significantly higher reduction in frequency of pain , in pain intensity ( visual analog scale [ VAS ] ) , and in a composite pain index ( intensity x frequency ) for patients treated with BI + OA compared with those treated with BI alone . In the BI + OA group , 60 % of the patients attained a clinical ly significant improvement ( at least 50 % or more ) on the pain index , a significantly higher proportion compared to that obtained in the other 2 treatment groups . Analgesic consumption was also significantly more reduced in the BI + OA group compared to the BI group . However , no significant differences were found between the treatment groups in jaw opening or in muscle and TMJ tenderness scores . Occlusal appliance was found to be superior to both relaxation therapy and brief information regarding pain reduction and can therefore be recommended when treating adolescents with TMD pain Objective To assess 1 ) the quality of reporting r and omised clinical trials in dental ( RCT -Ds ) and medical research ( RCT -Ms ) , 2 ) the quality of RCT reports in relation to the journal impact factor , 3 ) the source of funding , and 4 ) the quality of RCT -Ds in different areas of dental research . Design R and om sample s of 100 RCT -Ds and 100 RCT -Ms published in 1999 were evaluated for quality of reporting under blinded conditions with the Jadad quality assessment scale . In addition , correlation between the quality scores and journal impact factor or source of funding , as well as area of dental research were analysed . Results The quality of RCT -Ds and RCT -Ms published in 1999 was generally inadequate . The quality was largely equivalent in RCT -Ds and RCT -Ms . There was no correlation between the quality scores and the journal impact factor or the source of funding . Some differences were found in the quality scores between different areas of dental research . Conclusions The results from these RCT -Ds and RCT -Ms show that most of them were imperfect in the reporting of methodology and trial conduct . There is a clear need to improve the quality of trial reporting in dental and medical research OBJECTIVE To assess the method ological quality of the design and reporting of r and omized controlled trials published in one major dermatology specialty journal . DESIGN AND DATA SOURCES In a survey of all published parallel group r and omized controlled trials , we found 73 reports with allocation described as r and omized from all issues of Clinical and Experimental Dermatology from its inception in 1976 through 1997 . MAIN OUTCOME MEASURES Direct and indirect measures of the adequacy of r and omization , trial sample size , baseline comparisons , and intention-to-treat analysis . RESULTS H and search ing identified 73 r and omized controlled trials , but only 31 of these were found by search ing MEDLINE for the publication type clinical trials . Of the 73 r and omized controlled trials , 68 contained sufficient information to include in the analysis . Only 1 study ( 1 % ) reported the method of r and om sequence generation , and only 5 studies ( 7 % ) reported adequate concealment of allocation . Among 38 trials that used simple r and omization , the sample sizes in the comparison groups were identical in 22 occasions , raising the possibility that simple r and omization might not have been adequately generated or concealed . Most trials ( 88 % ) excluded some r and omized participants from their analysis . The median sample size was 23 per trial . Only 1 trial reported sample size and statistical power considerations and had an a priori main hypothesis . CONCLUSIONS H and search ing is important for locating all relevant trials . There is the need for higher method ological quality in clinical trial reporting in dermatology journals . The adoption of the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement and checklist for the reporting of trials should enhance the validity of and strengthen the evidence from clinical trials reports The " Consoli date d St and ards of Reporting Trials " ( CONSORT ) was developed to improve the suboptimal reporting of r and omized controlled trials ( RCTs ) . However , little is known about the quality of reporting since this publication . We undertook an observational study to determine the quality of reporting key method ological factors in RCTs since the publication of the CONSORT statement and if a journal policy to promote adherence to the CONSORT checklist was associated with superior reporting . We recorded the reporting of 11 key method ological factors in 105 RCTs from 29 medical journals published subsequent to the CONSORT statement . We examined the quality of reporting in relation to whether a journal was a " CONSORT promoter " as defined by inclusion of the CONSORT checklist in a journal 's " information to authors " section or a requirement that authors , manuscript review ers , or copy editors complete the CONSORT checklist . Multivariate analysis controlled for journal impact factor , study outcome , and time of publication . Six of the 11 method ological factors were reported < 50 % of the time . The number of method ological factors reported was greater in CONSORT promoters than in journals not promoting CONSORT in both unadjusted ( 6.0 and 5.1 , respectively , p-value = 0.03 ) and adjusted ( 6.4 and 4.8 of the 11 method ological factors , respectively , p-value = 0.0001 ) analyses . While journals that promote CONSORT demonstrate superior reporting of RCTs , persistent inadequacies in reporting remain . Until these inadequacies are resolved health-care providers will remain limited in their ability to make informed inferences about the validity of the studies upon which they base their clinical practice Abstract Objective . To assess the number and quality of the reporting of r and omised controlled trials ( RCTs ) published in Intensive Care Medicine . Design . Systematic revision . Setting R and omised controlled trials published in Intensive Care Medicine . Study selection . All RCTs published in this journal from its birth to December 2000 identified by MEDLINE and our own research . Measurements and results . The Jadad scale and the individual assessment of key method ological components , namely the r and omisation process , blinding and reporting and h and ling of loss to follow-up , were used to evaluate the quality of reporting . Other information was extracted regarding the design characteristics and the analytical approach . 173 RCTs , 63 % of which were from European countries , were analysed . Adequately reported RCTs according to a Jadad scale score of more than 2 were 44 ( 25.4 % ) . Analysis of individual method ological components revealed a variable percentage of adequate reporting ranging from 3.5 % for r and omisation to 10.4 % for blinding and to 49.1 % for loss to follow-up . Sample sizes were small with a median of 30 patients and rationale for its estimation was reported in 7.5 % . Despite this , 81.5 % of RCTs reported statistically significant results , suggesting that the treatment effects were strong or that a publication bias existed or that the uncertainty principle was not fulfilled . Conclusions . R and omised controlled trials offer the best evidence of the efficacy of medical interventions , provided that high st and ards of transparent reporting are used . More resolute attention to the method ological quality of reporting and adherence to recently published guidelines ( CONSORT II ) may help to achieve this result CONTEXT The evaluation of the method ologic quality of r and omized controlled trials ( RCTs ) is central to evidence -based health care . Important method ologic detail may , however , be omitted from published reports , and the quality of reporting is therefore often used as a proxy measure for method ologic quality . We examined the relationship between reporting quality and method ologic quality of published RCTs . METHODS Study of 60 reports of placebo-controlled trials published in English- language journals from 1985 to 1997 . Reporting quality was measured using a 25-item scale based on the 1996 issue of the Consoli date d St and ards of Reporting Trials ( CONSORT ) . Concealment of allocation , appropriate blinding , and analysis according to the intention-to-treat principle were indicators of method ologic quality . Method ologic quality was compared between groups of trials defined by reporting quality scores of low , intermediate , and high . Reporting quality scores were compared between groups defined by high and low method ologic quality . RESULTS Among 23 trials of low reporting quality ( median score , 9 [ range , 3.5 - 10.5 ] ) , allocation concealment was unclear for all but 1 trial , but there were 16 trials ( 70 % ) with adequate blinding and 9 trials ( 39 % ) that had been analyzed according to the intention-to-treat principle . Among 18 trials of high reporting quality ( median score , 18 [ range 16.5 - 22.0 ] ) , there were 8 trials ( 44 % ) with adequate allocation concealment , 16 trials ( 89 % ) with adequate blinding , and 13 trials ( 72 % ) analyzed according to the intention-to-treat principle . The median reporting score was 15.0 for the 33 trials that were analyzed according to intention-to-treat principle and 14.5 for the 14 trials with on-treatment analyses ( P = .67 ) . CONCLUSIONS Similar quality of reporting may hide important differences in method ologic quality , and well-conducted trials may be reported badly . A clear distinction should be made between these 2 dimensions of the quality of RCTs R and omized controlled trials ( RCTs ) are considered the most reliable type of clinical intervention studies . However , not all reports of RCTs are accessible in Medline . This can impede the validity of the results of systematic review s. Ten German- language dental journals were manually search ed to locate reports of controlled clinical trials published between 1970 and 2000 . The publication type was determined and compared with Medline . Of the 15 777 articles , 210 reports of RCTs and 410 articles of non-r and omized controlled clinical trials ( CCTs ) were identified . Only 56 % of the RCTs and 75 % of the CCTs are available in Medline . Of the 118 reports of RCTs registered in Medline . 15 are indexed with the correct Publication Type term . Our data suggest that ( a ) h and - search ing plays a valuable role in identifying reports of clinical dental trials , and ( b ) a literature search in Medline is likely to yield incomplete results Fifty-five patients ( 46 women and 9 men ) with craniom and ibular disorders and a history of pain of at least 6 months ' duration participated in this trial . The patients were r and omly assigned to three groups : one group to receive acupuncture ; one group to receive occlusal splint therapy ; and one group to act as controls . Pressure pain threshold , clinical dysfunction score , and visual analog scale measures were used to evaluate patients before , immediately after , and 6 months after treatment . A moderate , but statistically significant , correlation was found between pressure pain threshold and the number of tender spots in the masticatory muscles ( tau = -.43 ; P < .001 ) , degree of tenderness in the masticatory muscles ( tau = -.43 ; P < .001 ) , clinical dysfunction score ( tau = .32 ; P < .001 ) , and the visual analog scale ( tau = -.25 ; P < .01 ) . The short-term results showed a statistically significant improvement in all evaluations for both treatment groups . No significant differences were found in the control group . The improvements result ed in significant differences between the control and each treatment group immediately after treatment . At the 6-month follow-up , no significant differences in pressure pain threshold or clinical dysfunction score were found in the two treatment groups compared with the short-term results BACKGROUND / AIMS Electronic search es on data bases for r and omised clinical trials and controlled clinical trials do not identify as many trials as h and search es , and trial reporting may be flawed . The aims were to identify all fully reported r and omised clinical trials in the Journal of Hepatology and to make a qualitative assessment of the reporting . METHODS The publications were identified by systematic ally h and search ing the full text of the journal and search ing MEDLINE . Central dimensions of trial quality were used to assess the reporting quality of the trials . RESULTS R and omised clinical trials represented 8.4 % of the original articles ( 171/2028 ) . Ten original articles ( 0.5 % ) could not be classified . A search on MEDLINE identified 81.3 % of the r and omised clinical trials , i.e. , 139 out of the 171 identified by the h and search . A total of 166 r and omised clinical trials could be quality assessed . Forty-seven ( 28.3 % ) of them reported adequate generation of allocation sequence ; 22 ( 13.3 % ) adequate allocation concealment ; 95 ( 57.2 % ) allowed intention-to-treat analysis with only a few losses to follow-up ; 50 ( 30.1 % ) were double-blind ; 33 ( 19.9 % ) reported sample -size calculations ; 13 trials ( 7.8 % ) employed the crossover design ; and the median number of subjects per intervention arm in parallel group trials was 19 subjects ( interquartile range : 11 - 31 ; range : 5 - 519 ) . The quality of reporting was significantly better in regular issue articles than in supplement articles . CONCLUSIONS Many important r and omised clinical trials are published in the Journal of Hepatology , but there seems to be ample room for improvement of quality of reporting Eighty patients , of whom 22 were men and 58 women , participated in a 1-year follow-up study . All participants in the study showed signs and symptoms of craniom and ibular disorders ( CMD ) and had had pain for more than 6 months at treatment start . The patients were r and omly assigned to either acupuncture or occlusal splint therapy . Those patients who did not respond to either of the treatment modes were offered various additional therapies . The result showed that 57 % of the patients who received acupuncture and 68 % of the patients treated with occlusal splint therapy benefited subjectively ( p < 0.01 ) and clinical ly ( p < 0.001 ) from the treatment over a 12-month period . No statistically significant difference was found between the two groups as to the assessment variables . Those patients who received various additional therapies after acupuncture and /or occlusal splint therapy responded favorably to additional treatment in only a few instances . The study showed that acupuncture gave positive results similar to those of occlusal splint therapy in patients with primarily myogenic CMD symptoms over a 1-year follow-up period STATEMENT OF PROBLEM Soft and hard stabilizing appliances have been used to treat temporom and ibular disorders . No data exist to suggest whether a hard or soft appliance is beneficial . PURPOSE This study compared soft and hard acrylic resin stabilizing appliances in the reduction of masticatory muscle pain in patients with temporom and ibular disorders . MATERIAL S AND METHODS Twenty-three patients with at least one clinical sign from the list of diagnostic subgroups of temporom and ibular disorders were alternately assigned a hard or soft appliance for temporom and ibular disorder treatment . No other temporom and ibular disorder treatment ( self-care , physical therapy , biofeedback , or muscle or joint injections ) was rendered . Each patient was seen by two dentists at each visit . One dentist initially fabricated the appliance and adjusted the appliance on each visit and an examining dentist examined the patient each visit and recorded signs of temporom and ibular disorders . The appliance material ( soft or hard ) was not disclosed to the examining dentist , only to the dentist who fabricated and adjusted the appliance . Patients were examined and appliances were adjusted every 2 to 3 weeks for a minimum of 10 weeks . Masticatory muscles were palpated and charted on each visit . Data were analyzed and subjected to nonparametric Mann-Whitney test . RESULTS Eighteen of the initial 23 patients , 7 in the hard appliance group and 11 in the soft appliance group finished the study over 10- to 15-week period . Soft and hard appliances performed the same in reduction of masticatory muscle pain . CONCLUSION This study suggests , based on the limited number of participants , that soft and hard stabilizing appliances may be equally useful in reducing masticatory muscle pain in short-term appliance therapy Objective : To examine whether the stabilisation splint is a suitable treatment for pain dysfunction syndrome and to determine the most appropriate pattern of usage . Design : Prospect i ve r and om control clinical trial . Setting : Dental school clinic unit . Subjects : 70 patients diagnosed with pain dysfunction syndrome were treated with a stabilisation splint for 3 months . Group 1 ( 23 patients ) wore the splint 24 hours/day . Group 2 ( 19 patients ) wore the splint only during the day . Group 3 ( 28 patients ) wore the splint only at night . Results : There was no statistically significant advantage to any pattern of splint usage ; all groups showed a marked improvement by subjective and objective assessment . Conclusions : Patients being treated for pain dysfunction syndrome by a stabilisation splint need wear the splint only at PURPOSE The purpose s of this study were to compare changes in the condyle-fossa relationship in patients with temporom and ibular disorders of arthrogenous origin treated with either a stabilization or a control appliance in a double-blind controlled study , and to compare the changes in the condyle-fossa relationship with the short-term treatment effect in the two treatment groups . The radiographic appearance of the temporom and ibular joint was also studied . MATERIAL S AND METHODS Fifty-eight patients with temporom and ibular disorders of arthrogenous origin were assigned to two equally sized groups : a treatment group given a stabilization appliance ; and a control group , given a control appliance . The study covered 10 weeks . The treatment outcome regarding changes in severity of temporom and ibular joint pain on a verbal scale was compared to changes in the condyle-fossa relationship in horizontally corrected oblique lateral transcranial radiographs taken with and without the appliance . Condyle-fossa relationship and structural bone changes were observed before treatment in corrected lateral tomograms . RESULTS The group treated with a stabilization appliance showed a changed condylar position significantly more often ( P = 0.004 ) than the control group . Of the patients reporting a successful treatment outcome , significantly more ( P = 0.006 ) showed a changed condyle position in the group treated with a stabilization appliance than in the group treated with a control appliance . CONCLUSION In patients with temporom and ibular disorders of arthrogenous origin , the short-term occlusal appliance therapy result ing in a changed condylar position gave relief of symptoms more often than if the condylar position was unchanged Thirty subjects seeking treatment for masticatory muscle pain at a university-based TMJ clinic were r and omly assigned to soft-splint , palliative-treatment , and no-treatment groups . After 4 to 11 weeks of treatment , subjects were evaluated for changes from their baseline levels of symptoms , maximum pain-free opening , pain thresholds measured by a pressure algometer , and occlusal contacts . With the use of the multivariate analysis of variance and analysis of covariance , the results suggest that the soft-splint group had statistically significant improvement ( P < .01 ) , the palliative-treatment group had improvement that was not statistically significant , and the no-treatment group had a slight aggravation of symptoms . The soft-splint group had fewer occlusal contact changes assessed with shimstock compared to the palliative-treatment and no-treatment groups . The findings of this study suggest that the soft splint is an effective short-term treatment for reducing the signs and symptoms of masticatory muscle pain in patients , and the soft splint does not cause occlusal changes Twenty patients with m and ibular dysfunction , all women , aged 17 - 41 years , were r and omized for treatment with either a bite plate with a frontal plateau or a full-coverage stabilization splint . The occlusal appliances were used at night for 6 weeks to compare clinical and electromyographic effects ( EMGs ) . Integrated EMGs were recorded bilaterally from the anterior and posterior parts of the temporal muscle and the masseter muscle in the rest position and during gentle and maximal biting before and after treatment without the appliances in situ . Initially recorded EMG activity in the temporal muscle was correlated to signs of dysfunction in the rest position . Compared with previously investigated healthy subjects , the patients had lower EMG activity in the anterior part of the temporal muscle and in the masseter muscle during maximal biting . Use of occlusal appliances at night for 6 weeks did not change the EMG activity in the rest position or during maximal biting . The clinical signs improved , significantly in the splint group . The subjective symptoms improved in both groups , significantly more in the splint group There is controversial evidence for a functional link between the masticatory apparatus and the cervical spine . The aim of this work was to perform a preliminary study to evaluate the effectiveness of the Michigan splint for the treatment of functional cervical disturbances . Forty patients with functional cervical disturbances were r and omly organized into test and control groups . The patients in each group were examined by a physiologist to ascertain the extent of functional changes . The test group underwent splint therapy ( Michigan type ) during a two-month period . The other patients were sent home and did not receive active treatment . After two months , all patients were reassessed physiologically . Cervical pain and pain induced by epispinal or paraspinal pressure were reduced to a statistically significant extent in the treated group , compared with those in the control group This research compares different treatment regimes for the management of chronic facial pain associated with the masticatory musculature . Twenty-one females meeting specific criteria were r and omly assigned to one of three treatment conditions : a dental splint and physiotherapy program ; a relaxation program utilizing progressive muscle relaxation , biofeedback , and stress management techniques ; or a minimal treatment program involving transcutaneous electrical nerve stimulation . Improvement was assessed through a dental examination , self-monitoring of pain , and an assessment of EMG activity during resting and task conditions . Significant changes were obtained in response to all treatment programs . The treatment programs differed only in the relative pattern of treatment effects obtained from the self-report monitoring of pain . The data are consistent with the concept of MPD as a psychological response to stress which maintains chronic pain through increased muscle tension in the jaw A flat occlusal splint has been extensively used in the treatment of patients with temporom and ibular joint disk displacement without reduction , but no studies with untreated controls have assessed its effect . We r and omly assigned 51 patients with temporom and ibular joint pain and arthrographically verified disk displacement without reduction to be treated with a flat occlusal splint or to serve as untreated control subjects in a 12-month clinical trial . Pain symptoms disappeared in about one third of the patients in each group . Another third of the patients in the control group improved . Sixteen percent of the patients in the control group and 40 % of the patients treated with a flat occlusal splint were worse at the end than at the beginning of the study . Joint pain and muscle tenderness decreased more frequently in the nontreatment controls than in the treatment group . A statistically significant benefit of a flat occlusal splint over nontreatment control subjects could not be identified in this study of patients with painful disk displacement without reduction . The use of a flat occlusal splint in this patient group should therefore be reconsidered BACKGROUND The research literature reaches inconsistent conclusions about the efficacy of oral splints for treating myofascial face pain . This investigation hypothesizes that their effectiveness varies as a function of the presence or absence of widespread pain . METHODS In a r and omized , controlled clinical trial , 63 women with myofascial face pain were assigned to use of either an active , maxillary , flat-plane , hard acrylic splint or a palatal splint that did not interfere with occlusion . Participants also were classified according to the presence or absence of widespread pain throughout the body . After six weeks , groups were compared regarding pain on palpation , self-reported pain and functional outcome . RESULTS Overall , the findings showed a modest tendency for subjects receiving the active vs. the palatal splint to exhibit improvement on self-reported pain and functional outcome . On further division of the sample into subjects with local vs. widespread pain , the general pattern showed that patients with widespread pain who received an active splint did not experience improvement , while patients with local pain who received the active splint did . CONCLUSIONS The presence or absence of widespread pain may help to define the specific circumstances under which oral splints should be prescribed for patients with myofascial face pain . CLINICAL IMPLICATION S Clinicians should screen patients with myofascial face pain for the presence of widespread pain , since this comorbid symptom pattern may be a contraindication for the use of oral splints The aim of this thesis was to prospect ively evaluate the short-term effect of a non-steroidal anti-inflammatory drug ( diclofenac sodium , Voltaren ) and stabilisation appliance in controlled trials of patients with temporom and ibular disorders ( TMD ) of arthrogeneous origin . The active treatments were compared to placebo in the study of diclofenac and to a control appliance in the other study . Thirty-two patients in the first study and 60 patients in the second study were r and omly assigned into two equally large groups . In the second study two different techniques regarding assessment of changes in condylar position on radiographs with and without an occlusal appliance was evaluated . Changes in condyle-fossa relationship was compared in the two patient groups , and the changes in condyle-fossa relationship was compared with the treatment outcome between the two treatment groups . The influence of possible background variables on outcome of treatment with occlusal appliances were tested . The group treated with diclofenac did not seem to have recovered better from TMD than placebo . However , in the other study the group treated with a stabilisation appliance showed a better treatment outcome , with respect to both symptoms and signs , than the group treated with a control appliance . The group treated with a stabilisation appliance more often showed a changed condylar position in the transcranial radiographs of the TMJ than the group treated with a control appliance . It was also shown that the patients treated with a stabilisation appliance more often experienced relief of TMD symptoms when the stabilisation appliance had achieved a changed condyle-fossa relationship . Treatment with a stabilisation appliance was still a strong explanatory factor when testing possible background variables for a positive treatment outcome , but also male sex ( positive ) and severe or very severe TMJ pain ( negative ) influenced the treatment outcome . It was concluded that there was no evidence to suggest that diclofenac sodium ( Voltaren ) should be used as a primary treatment for TMJ pain in patients with TMD . However , the stabilisation appliance is recommended for the treatment of patients with TMD suffering from TMJ pain . ( Less Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale ABSTRACT Loss of function , muscle inflammation , and pain are some of the signs and symptoms of temporom and ibular dysfunction ( TMD ) . Pharmacological strategies to minimize the clinical manifestation of these disorders often focus on blocking or inhibiting the pain-causing symptom . Re sources such as muscle-relaxants , anxiety-relief drugs , and splint therapy are often used to reduce muscular hyper-activity related to TMD muscle pain . This study compares the effect of a r and omly ordered association of occlusal splint therapy ( S ) , nonsteroid anti-inflammatory with a muscle-relaxant drug ( orphenadrine citrate ) ( O ) , and an anxiety-relief drug ( benzodiazepine ) ( B ) , to ease painful TMD muscle symptoms . Clinical and anamnestic analyses were recorded in accordance with the Helkimo TMD index and applied before and after treatments . Twenty-one group two Helkimo TMD adult female patients were treated , all of whom were subjected to the three r and om therapeutic associations proposed : SBO , BOS , and OSB . The same operator applied the three specific associations over a period of 21 days in the proposed sequence , seven days for each therapy . The results show that all the groups presented the best results in terms of relief from pain after the therapeutic association ( 28.5 % showed a decrease and 47.6 % showed an absence of symptoms ) . No significant difference was observed among association therapeutic protocol BACKGROUND Lately , the number of systematic review s published has increased substantially . Many systematic review s exclude trials published in language s other than English . However , there is little empirical evidence to support this action . We looked for differences in the completeness of reporting between trials published in other language s and those published in English , to see whether the exclusion of trials published in other language s is justified . METHODS We compared completeness of reporting , design characteristics , and analytical approaches of 133 r and omised controlled trials ( RCTs ) published in English between 1989 and 1994 and 96 published in French , German , Italian , or Spanish during the same time . RCTs were identified by h and search ing of journals ( seven in English and six in the other language s ) . FINDINGS We found no significant differences between trials published in English and other- language trials for any single item in the completeness of reporting scale ( r and omisation , double-blinding , withdrawals ) , or for the overall score ( percentage of maximum possible score 51.0 % for trials in English , 46.2 % for trials in other language s ; 95 % CI for difference -1.1 to 10.5 ) . Other- language trials were more likely than English- language trials to have adult participants , to use two or more interventions , and to compare two or more active treatments without an untreated control group . Trials in other language s were less likely to report a clearly prespecified primary outcome or any rationale for sample size estimation . INTERPRETATION These results provide evidence for inclusion of all trial reports , irrespective of the language in which they are published , in systematic review s. Their inclusion is likely to increase precision and may reduce systematic errors . We hope that our findings will prove useful to those developing guidelines and policies for the conduct of reporting of systematic review BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline . Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias & NA ; Oral splints are widely used in the treatment of myofascial pain of masticatory muscles , even though their mechanism of action is unknown . The present study evaluated the therapeutic efficacy of splints using a parallel , r and omized , controlled and blind design . Following a sample size estimation , 63 subjects were recruited and assigned to 3 groups : ( 1 ) passive control : full occlusal splint worn only 30 min at each appointment : ( 2 ) active control : palatal splint worn 24 h/day : and ( 3 ) treatment : full occlusal splint worn 24 h/day . On each of 7 visits over 10 weeks , subjects rated on 100 mm visual analogue scales their pain intensity and unpleasantness at rest and after experimental mastication . The effect of pain on the quality of life was also rated on category scales . All pain ratings decreased significantly with time , and quality of life improved for all 3 groups . However , there were no significant differences between groups in any of the variables . These data suggest that the gradual reduction in the intensity and unpleasantness of myofascial pain , as well as the improvement of quality of life during the trial , was non‐specific and not related to the type of treatment Occlusal splints constructed at three different vertical heights were used to study the influence of vertical dimension in the etiology of bruxism and MPD syndrome . The vertical dimension of least EMG activity was determined for each of 75 patients who were r and omly divided into three groups according to the vertical dimension at which the occlusal splint was constructed . Group I occlusal splints were constructed at 1 mm from the occlusal vertical dimension , group II splints at 4.42 mm , and group III splints at 8.15 mm . Results showed a faster and more complete reduction in clinical symptoms for groups II and III than for group I. The temporary use of occlusal splints with a vertical height exceeding the physiologic rest position did not encourage a greater muscular tonus or hyperactivity of jaw muscles . It can be concluded that elongation of elevator muscles to or near the vertical dimension of least EMG activity by means of occlusal splints is more effective in producing neuromuscular relaxation |
13,585 | 32,203,236 | Adult weight gain may be associated with a higher risk of CVD .
Measuring weight gain during adulthood may be better than static , cross-sectional assessment of weight because it considers trend over time , and thus , can be used as a supplementary approach to predict CVD | We aim ed to examine the association of weight gain during adulthood with the risk of cardiovascular disease ( CVD ) in the general population . | Background The association between change in weight or body mass index , and mortality is widely reported , however , both measures fail to account for fat distribution . Change in waist circumference , a measure of central adiposity , in relation to mortality has not been studied extensively . Methods We investigated the association between mortality and changes in directly measured waist circumference , hips circumference and weight from baseline ( 1990–1994 ) to wave 2 ( 2003–2007 ) in a prospect i ve cohort study of people aged 40–69 years at baseline . Cox regression , with age as the time metric and follow-up starting at wave 2 , adjusted for confounding variables , was used to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for change in body size in relation to mortality from all causes , cardiovascular disease and cancer . Results There were 1465 deaths ( 109 cancer , 242 cardiovascular disease ) identified during an average 7.7 years of follow-up from 21 298 participants . Compared to minimal increase in body size , loss of waist circumference ( HR : 1.26 ; 95 % CI : 1.09–1.47 ) , weight ( 1.80 ; 1.54–2.11 ) , or hips circumference ( 1.35 ; 1.15–1.57 ) were associated with an increased risk of all-cause mortality , particularly for older adults . Weight loss was associated with cardiovascular disease mortality ( 2.40 ; 1.57–3.65 ) but change in body size was not associated with obesity-related cancer mortality . Conclusion This study confirms the association between weight loss and increased mortality from all-causes for older adults . Based on evidence from observational cohort studies , weight stability may be the recommended option for most adults , especially older adults Studies have reported a higher mortality risk associated with weight loss , particularly in middle-aged and older adults , although some of these studies did find that gaining weight was also associated with an increased mortality risk . We examined changes in weight in relation to mortality in a prospect i ve population -based cohort study of men and women , resident in Norfolk , UK . Participants were assessed at baseline ( 1993–1997 ) and at a second examination ( 1998–2000 ) , as part of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Norfolk ) study , and followed up to 2015 for mortality . Participants with a self-reported history of cancer or cardiovascular disease , body mass index < 18.5 kg/m2 or missing data on adjustment variables , at either time-point were excluded , leaving 12,580 participants , aged 39–78 in 1993–1997 , eligible for analyses . Cox proportional hazards models were used to determine Hazard Ratios ( HRs ) for all-cause ( 2603 deaths ) , cardiovascular ( 749 deaths ) , cancer ( 981 deaths ) , respiratory ( 226 deaths ) and other causes of mortality ( 647 deaths ) by categories of weight change . After multivariate adjustment , the HRs ( 95 % CIs ) for all-cause mortality for men and women who lost more than 5 kg were 1.85 ( 1.48–2.31 ) and 1.64 ( 1.31–2.05 ) respectively . Higher hazards were also found for specific causes of mortality and weight loss > 5 kg . Similar associations were observed after excluding deaths in the first 5 years of follow-up . Results for weight gain were inconclusive . We conclude that objective ly measured weight loss , but not weight gain , was associated with subsequent higher mortality risk in this population -based study of middle-aged and elderly men and women . However , undiagnosed , pre-existing disease and the inability to account for weight cycling need to be remembered when interpreting these results . Unravelling the causal pathways underlying this association will require more detailed studies , including that of changes in body composition Although 25 % of US men indicate that they are trying to lose weight , the association between intentional weight loss and longevity in men is unknown . The authors analyzed prospect i ve data from 49,337 overweight ( initial body mass index > or = 27 ) white men aged 40 - 64 years who , in 1959 - 1960 , answered questions on weight change direction , amount , time interval , and intent . Vital status was determined in 1972 . Proportional hazards regression estimated mortality rate ratios for men who intentionally lost weight compared with men with no weight change . Analyses were stratified by health status and adjusted for age , initial body mass index , smoking status , alcohol intake , education , physical activity , health history , and physical symptoms . Among men with no reported health conditions ( n = 36,280 ) , intentional weight loss was not associated with total , cardiovascular ( CVD ) , or cancer mortality , but diabetes-associated mortality was increased 48 % ( 95 % confidence interval ( CI ) -7 % to + 133 % ) among those who lost 20 pounds ( 9.1 kg ) or more ; this increase was largely related to non-CVD mortality . Among men with reported health conditions ( n = 13,057 ) , intentional weight loss had no association with total or CVD mortality , but cancer mortality increased 25 % ( 95 % confidence interval -4 % to + 63 % ) among those who lost 20 pounds or more . Diabetes-associated mortality was reduced 32 % ( 95 % confidence interval -52 % to -5 % ) among those who lost less than 20 pounds and 36 % ( 95 % confidence interval -49 % to -20 % ) among those who lost more than 20 pounds . These results and those from our earlier study in women ( Williamson et al. , Am J Epidemiol 1995;141:1128 - 41 ) suggest that intentional weight loss may reduce the risk of dying from diabetes , but not from CVD . In observational studies , however , it is difficult to separate intentional weight loss from unintentional weight loss due to undiagnosed , underlying disease . Well- design ed observational studies , as well as r and omized controlled trials , are needed to determine whether intentional weight loss reduces CVD mortality OBJECTIVE The prevalence of obesity is increasing in many European countries and in the United States . This report examines the mortality and morbidity associated with being overweight and obese in the Caerphilly Prospect i ve Study and the relative effects of weight in middle age and self reported weight at 18 years . DESIGN All men aged 45 to 59 years from the town of Caerphilly , South Wales and outlying villages were identified and 2512 men were examined for the first time between 1979 and 1983 . Men were asked to recall their weight at 18 years of age ( when the majority had been examined for National Service ) so that weight then , weight at screening , and the difference could be related to their 14 year follow up from screening . A total of 2335 men could recall their weight at 18 years . By 14 years of follow up from screening 465 men had died and 382 had had coronary events . RESULTS Mean body mass index in men who reported their weight at 18 years was 22.3 ( SD 2.8 ) kg/m2 and only 41 of these men ( 1.8 % ) were classified as obese ( index ⩾ 30 kg/m2 ) . The index did not predict all cause mortality when examined by quintile . For major ischaemic heart disease ( non-fatal or fatal ischaemic heart disease ) the relative odds was 1.73 ( 95 % CI 1.21 , 2.48 ) in the top fifth of the distribution ( body mass index ⩾ 24.2 kg/m2 ) compared with the bottom fifth ( body mass index < 20.1 kg/m2 ) . In men with an index ⩾ 30 kg/m2 however , the relative odds were 2.03 ( 95 % CI , 1.03 , 4.01 ) for all cause mortality and 2.17 ( 95 % CI , 1.08 , 4.34 ) for major ischaemic heart disease , adjusted for age , smoking habit and social class . When men were recruited to the study , from 1979 to 1983 ; the mean body mass index had increased to 26.2 ( SD 3.6 ) , a mean increase of 3.9 kg/m2 or 11.2 kg ; 299 men ( 12.1 % ) were classified as obese and showed significantly increased relative odds of both all cause mortality ( 1.53 ( 95 % CI 1.14 , 2.06 ) and major ischaemic heart disease ( 1.55 ( 95 % CI 1.13 , 2.11 ) ) , adjusted for age , smoking habit and social class relative to the non-obese men . The effect of gain in weight from 18 years to recruitment was also examined ; all cause mortality showed highest mortality in the fifth of the distribution who experienced weight loss or minimal weight gain . For major ischaemic heart disease an inconsistent , weak trend was shown , the relative odds rising to a maximum of 1.26 ( 0.89 , 1.80 ) in the top fifth of weight gain compared with the bottom fifth . Weight gain showed strong associations with potential cardiovascular risk factors measured at recruitment ; insulin , triglyceride , glucose , diastolic and systolic blood pressure and high density lipoprotein-cholesterol . CONCLUSIONS Body mass at 18 years of age of 30 kg/m2 or more conferred increased risk for all cause mortality and major ischaemic heart disease during 14 years of follow up of men aged 45 to 59 years . By the baseline examination the prevalence of obesity ( body mass index ⩾30 ) had increased from 1.8 % to 12.1 % ; obese men also showed an excess risk of major ischaemic heart disease and overall mortality , but these risks were lower than those predicted from 18 years of age . Weight gain was strongly associated with smoking habit , the greatest weight gain being among ex-smokers and the least among light smokers . Weight gain from 18 years of age to baseline examination showed little relation with subsequent mortality and risk of major ischaemic heart disease when adjusted for age , smoking habit and social class . The lowest mortality rate occurred in the “ fifth ” of men who gained a mean weight of 16.1 kg . Weight gain is closely associated with some adverse cardiovascular risk factors ; in particular with insulin , triglyceride , glucose and diastolic blood pressure 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 Although 40 % of US women indicate they are currently trying to lose weight , the association between intentional weight loss and longevity is unknown . The authors analyzed prospect i ve data from 43,457 overweight , never-smoking US white women aged 40 - 64 years who in 1959 - 1960 completed a question naire that included questions on weight change direction , amount , time interval , and intentionality . Vital status was determined in 1972 . Proportional hazards regression was used to estimate mortality rate ratios for women who intentionally lost weight compared with women who had no change in weight . Women who died within the first 3 years of follow-up were excluded . Analyses were stratified by preexisting illness and adjusted for age , beginning body mass index , alcohol intake , education , physical activity , and health conditions . In women with obesity-related health conditions ( n = 15,069 ) , intentional weight loss of any amount was associated with a 20 % reduction in all-cause mortality , primarily due to a 40 - 50 % reduction in mortality from obesity-related cancers ; diabetes-associated mortality was also reduced by 30 - 40 % in those who intentionally lost weight . In women with no preexisting illness ( n = 28,388 ) , intentional weight loss of > or = 20 lb ( > or = 9.1 kg ) that occurred within the previous year was associated with about a 25 % reduction in all-cause , cardiovascular , and cancer mortality ; however , loss of < 20 lb ( < 9.1 kg ) or loss that occurred over an interval of > or = 1 year was generally associated with small to modest increases in mortality . The association between intentional weight loss and longevity in middle-aged overweight women appears to depend on their health status . Intentional weight loss among women with obesity-related conditions is generally associated with decreased premature mortality , whereas among women with no preexisting illness , the association is equivocal 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 : To evaluate the association between weight variability and disease incidence in women . DESIGN : Prospect i ve cohort study , following women from 1986 through 1992 . METHODS : A population -based sample of 33 834 women aged 55–69 y , free of cancer and heart disease , completed a mail-based survey that included self-reported body weights at ages 18 , 30 , 40 , 50 y , and currently . Weight variability was defined as ( 1 ) the root mean square error around the slope of weight on age ( RMSE ) ; and ( 2 ) categorical measures of weight change . Outcome measures were incidence of myocardial infa rct ion ( MI ) ; stroke ; diabetes ; breast , endometrial , lung , or other cancer ; total and hip fractures . RESULTS : Adjusted relative risks of MI , stroke , diabetes , and hip fracture increased with increasing weight variability . The age and body mass index-adjusted relative risks ( RR ) for highest vs lowest quartile of RMSE were : MI : 2.03 ; stroke : 1.61 ; diabetes : 1.42 ; breast cancer : 0.85 ; endomentrial cancer : 0.88 ; lung cancer : 1.70 ; other cancer : 0.93 ; total fractures : 1.15 ; hip fractures : 1.45 . The strongest associations between weight change categories and disease were for diabetes ( RR compared to small gain/stable weight : large cycle , 1.72 ; small cycle , 1.55 ; large gain , 1.80 ; weight loss , 1.91 ; other pattern , 1.55 ) . Large weight cycles were associated with higher risk of MI ( RR=1.89 ) and stroke ( RR=1.71 ) . CONCLUSIONS : These findings are consistent with previous studies and suggest that weight variability is associated with higher risk of developing chronic diseases OBJECTIVE To examine the associations of body mass index ( BMI ) and weight change with risk of stroke in women . SETTING AND DESIGN Prospect i ve cohort study among US female registered nurses participating in the Nurses ' Health Study . PARTICIPANTS A total of 116759 women aged 30 to 55 years in 1976 who were free from diagnosed coronary heart disease , stroke , and cancer . MAIN OUTCOME MEASURE Incidence of ischemic stroke , hemorrhagic stroke ( subarachnoid or intraparenchymal hemorrhage ) , and total stroke . RESULTS During 16 years of follow-up , 866 total strokes ( including 403 ischemic strokes and 269 hemorrhagic strokes ) were documented . In multivariate analyses adjusted for age , smoking , postmenopausal hormone use , and menopausal status , women with increased BMI ( > or = 27 kg/m2 ) had significantly increased risk of ischemic stroke , with relative risks ( RRs ) of 1.75 ( 95 % confidence interval [ CI ] , 1.17 - 2.59 ) for BMI of 27 to 28.9 kg/m2 ; 1.90 ( 95 % CI , 1.28 - 2.82 ) for BMI of 29 to 31.9 kg/m2 ; and 2.37 ( 95 % CI , 1.60 - 3.50 ) for BMI of 32 kg/m2 or more ( P for trend<.001 ) , as compared with those with a BMI of less than 21 kg/m2 . For hemorrhagic stroke there was a nonsignificant inverse relation between obesity and hemorrhagic stroke , with the highest risk among women in the leanest BMI category ( P for trend=.20 ) . For total stroke the RRs were somewhat attenuated compared with those for ischemic stroke but remained elevated for women with higher BMI ( P for trend<.001 ) . In multivariate analyses that also adjusted for BMI at age 18 years , weight gain from age 18 years until 1976 was associated with an RR for ischemic stroke of 1.69 ( 95 % CI , 1.26 - 2.29 ) for a gain of 11 to 19.9 kg and 2.52 ( 95 % CI , 1.80 - 3.52 ) for a gain of 20 kg or more ( P for trend<.001 ) , as compared with women who maintained stable weight ( loss or gain < 5 kg ) . Although weight change was not related to risk of hemorrhagic stroke ( P for trend=.20 ) , a direct relationship was observed between weight gain and total stroke risk ( P for trend<.001 ) . CONCLUSIONS These prospect i ve data indicate that both obesity and weight gain in women are important risk factors for ischemic and total stroke but not hemorrhagic stroke . The relationship between obesity and total stroke depends on the distribution of stroke subtypes in the population OBJECTIVE To determine how change in BMI over 8 years is associated with risk of subsequent cardiovascular disease ( CVD ) among middle aged men . METHODS Prospect i ve cohort study among 13,230 healthy men ( aged 51.6+/-8.7 years ) in the Physicians ' Health Study . BMI was collected at baseline in 1982 and after 8 years , at which time follow-up began . Subsequent CVD events were collected and confirmed through March 31 , 2005 . Cox proportional hazards models evaluated BMI at 8 years and risk of CVD , 8-year change in BMI and risk of CVD , and whether change in BMI added prognostic information after the consideration of BMI at 8 years . RESULTS 1308 major CVD events occurred over 13.5 years . A higher BMI at year 8 was associated with an increased risk of CVD . Compared to a stable BMI ( + /-0.5 kg/m(2 ) ) , a 0.5 - 2.0 kg/m(2 ) increase had a multivariable-adjusted RR of 1.00 ( 0.86 - 1.16 ) . A > /=2.0 kg/m(2 ) increase had a multivariable-adjusted RR of 1.39 ( 1.16 - 1.68 ) , however further adjustment for BMI reduced the RR to 1.00 ( 0.81 - 1.23 ) . A decrease in BMI had a multivariable RR of 1.23 ( 1.07 - 1.42 ) which was unaffected by adjustment for BMI at 8 years . CONCLUSION A higher BMI and a rising BMI were both associated with an increased risk of CVD , however an increasing BMI did not add prognostic information once current BMI was considered . In contrast , a declining BMI was associated with an increased risk of CVD independent of current BMI Obesity , and roid fat distribution , and other anthropometric measures have been associated with coronary heart disease in long-term prospect i ve studies . However , fluctuations in weight due to age-related hormonal changes and changes in lifestyle practice s may bias relative risk estimates over a long follow-up period . The authors prospect ively studied the association between body mass index ( BMI ) ( kg/m2 ) , waist-to-hip ratio , and height as independent predictors of incident coronary heart disease in a 3-year prospect i ve study among 29,122 US men aged 40 - 75 years in 1986 . The authors documented 420 incident coronary events during the follow-up period . Body mass index , waist-to-hip ratio , short stature , and weight gain since age 21 were associated with an increased risk of coronary heart disease . Among men younger than 65 , after adjusting for other coronary risk factors , the relative risk was 1.72 ( 95 % confidence interval ( CI ) 1.10 - 2.69 ) for men with BMI of 25 - 28.9 , 2.61 ( 95 % CI 1.54 - 4.42 ) for BMI of 29.0 - 32.9 , and 3.44 ( 95 % CI 1.67 - 7.09 ) for obese men with BMI > or = 33 compared with lean men with BMI < 23.0 . Among men > or = 65 years of age , the association between BMI and risk of coronary heart disease was much weaker . However , in this age group , the waist-to-hip ratio was a much stronger predictor of risk ( relative risk = 2.76 , 95 % CI 1.22 - 6.23 between extreme quintiles ) . These results suggest that for younger men , obesity , independent of fat distribution , is a strong risk factor for coronary heart disease . For older men , measures of fat distribution may be better than body mass index at predicting risk of coronary disease Background : Obesity and weight gain are associated with increased risk of coronary heart disease in Western countries . However , their impact is not well eluci date d in Asia , where body mass index ( BMI ) levels are generally lower than in Western countries . We examined associations of BMI ( kg/m2 ) and weight change with risk of coronary heart disease in Japanese people . Methods and results : A total of 43 235 men and 47 444 women aged 40–69 years living in communities were followed up from 1990 to 2001 in the Japan Public Health Center-based ( JPHC ) prospect i ve study . During 879 619 person-years of follow-up , we documented 399 cases of coronary heart disease ( 334 myocardial infa rct ion and 65 sudden cardiac death ) for men and 119 ( 95 myocardial infa rct ion and 24 sudden cardiac death ) for women . Compared with persons with BMI 23.0–24.9 , men , but not women , with BMI ⩾30.0 had higher risk of coronary heart disease and myocardial infa rct ion ; the multivariable relative risks for men were 1.8 ( 1.1–3.0 ) and 1.9 ( 1.1–3.2 ) , respectively . When weight change was examined according to BMI at age 20 years , men with initial BMI < 21.7 who gained more than 10 kg compared with men of no weight change had a twofold higher risk of coronary heart disease . Both men and women with initial BMI ⩾21.7 showed no association between weight loss and the risk . Conclusions : High BMI was associated with increased risk of coronary heart disease among men . Also , weight gain was associated with increased risk among lean men OBJECTIVES To delineate the association of weight with cardiovascular health throughout adulthood . METHODS We conducted a population -based prospect i ve cohort study of 26 097 community-dwelling individuals who were followed for 11.4 years with measurements of cardiovascular risk factors and common chronic disorders . Body weight and height were directly measured at baseline in 1995 - 1997 as they had been 10 and 30 years prior to baseline . From these measurements , we estimated average body mass index ( BMI ) over time and calculated weight change . RESULTS The association of average BMI with acute myocardial infa rct ion ( AMI ) became weaker with adjustment for the most recent BMI measurement , whilst this adjustment had a more limited effect on associations with heart failure ( HF ) risk . For example , the multi-adjusted hazard ratios for AMI in a comparison of individuals with average BMI until baseline ≥35 kg m(-2 ) and between 18.5 and 22.4 kg m(-2 ) decreased from 1.75 [ 95 % confidence interval ( CI ) 1.04 - 2.95 ] to 1.32 ( 0.73 - 2.40 ) . The corresponding numbers for HF were 3.12 ( 1.85 - 5.27 ) and 2.95 ( 1.53 - 5.71 ) , respectively . The associations between weight change and risk of AMI and HF were U-shaped , with stable weight showing the lowest risk . CONCLUSION Sustained overweight or obesity over time is associated with increased risk of HF , even after adjustment for the most recent BMI . For AMI risk , the most recent BMI appears to be the most important . Weight change also increases risks for both outcomes beyond the effects of BMI . Our results suggest that a global epidemic of obesity is likely to increase the incidence of HF , even if BMI in middle age can be controlled BACKGROUND Weight gain is an important risk factor of coronary artery disease , but there is limited evidence for an effect of weight change on heart failure ( HF ) mortality . METHODS AND RESULTS A total of 61,571 subjects aged 40 - 79 years were selected . Participants were already enrolled in the Japan Collaborative Cohort ( JACC ) study , for whom data regarding weight at the age of 20 years of age were available . The underlying causes of death were determined based on the International Classification of Diseases . During the median 19.3-year follow-up of the cohort , there were 640 deaths from myocardial infa rct ion ( MI ) and 605 deaths from HF . Men and women who had gained weight had a higher risk of mortality from MI , whereas those who had lost weight had a higher risk of mortality from HF . Compared to subjects with no weight change ( within ±5.0 kg ) , the multivariate hazard ratios ( HR ; 95 % confidence interval [ CI ] ) of MI for weight change of + 10.0 kg or more were 1.51 ( 1.11 - 2.06 ) for men and 1.80 ( 1.23 - 2.64 ) for women , whereas HRs of HF were 0.76 ( 0.51 - 1.13 ) and 0.94 ( 0.66 - 1.33 ) , respectively . The corresponding HRs of MI for weight change of -10.0 kg or more were 0.86 ( 0.57 - 1.31 ) for men and 0.90 ( 0.54 - 1.53 ) for women , whereas those of HF were 1.33 ( 0.93 - 1.89 ) and 1.48 ( 1.04 - 2.12 ) , respectively . CONCLUSIONS High BMI and weight gain are associated with increased risk of mortality from MI , whereas low BMI and weight loss are associated with increased risk of mortality from HF . ( Circ J 2014 ; 78 : 649 - 655 ) of Anesthesiologists Task Force on Management of the Difficult Airway . Anesthesiology 2013 ; 118 : 251–70 11 . Japanese Society of Anesthesiologists . JSA airway management guideline 2014 : to improve the safety of induction of anesthesia . J Anesth 2014 ; 28 : 482–93 12 . Asai T , Barclay K , Power I , Vaughan RS . Cricoid pressure impedes the placement of the laryngeal mask airway . Br J Anaesth 1995 ; 74 : 521–5 13 . Hashimoto Y , Asai T , Arai T , Okuda Y. Effect of cricoid pressure on placement of the I-gelTM : a r and omised study . Anaesthesia 2014 ; 69 : 878–82 14 . Asai T , Liu EH , Matsumoto S , et al. Use of the Pentax-AWS in 293 patients with difficult airways . Anesthesiology 2009 ; 110 : 898–904 15 . Liu EHC , Goy RWL , Tan BH , Asai T. Tracheal intubation with videolaryngoscopes in patients with cervical spine immobilization : a r and omized trial of the Airway Scope ® and the GlideScope ® . Br J Anaesth 2009 ; 103 : 446–51 16 . Rosenblatt W , Ianus AI , Sukhupragarn W , Fickenscher A , Sasaki C. Preoperative endoscopic airway examination ( PEAE ) provides superior airway information and may reduce the use of unnecessary awake intubation . Anesth Analg 2011 ; 112 : 602–7 17 . Tachibana N , Niiyama Y , Yamakage M. Incidence of can not intubate-cannot ventilate ( CICV ) : results of a 3-year retrospective multicenter clinical study in a network of university hospitals . J Anesth 2015 ; 29 : 326–30 18 . Asai T. Strategies for difficult airway management — the current state is not ideal . J Anesth 2013 ; 27 : BACKGROUND Weight loss and fluctuations in weight have been associated with increased risks of death from cardiovascular disease and from all causes . The clinical and public health implication s of these associations are unclear . METHODS We examined the long-term relation of weight change and fluctuation in weight with mortality over a 6-year period in 6537 middle-aged Japanese American men enrolled in the Honolulu Heart Program , a prospect i ve study ( mean follow-up , 14.5 years ) . RESULTS Men who had a weight loss of 4.5 kg or more or who had large fluctuations in weight ( or both ) over a six-year period were , on average , in poorer health than their peers whose weight was more stable . After the exclusion of subjects who died during the first five years of follow-up and after adjustment for confounding factors , a weight loss of more than 4.5 kg was associated with the risk of death from all causes , with the exception of death from cancer . The subjects whose weight fluctuated the most had a significantly higher risk of death from cardiovascular causes ( relative risk , 1.41 ; 95 percent confidence interval , 1.03 to 1.93 ) , death from noncardiovascular and noncancerous causes ( relative risk , 1.53 ; 95 percent confidence interval , 1.12 to 2.10 ) , and death from all causes ( relative risk , 1.25 ; 95 percent confidence interval , 1.05 to 1.48 ) . However , the associations of weight loss and variation in weight with death from cardiovascular causes and from noncardiovascular and noncancerous causes were not found among healthy men who had never smoked . CONCLUSIONS The associations between weight loss or fluctuation and mortality were partially explained by confounding factors and by the presence of preexisting disease . However , weight loss and weight fluctuation were unrelated to death among healthy men who had never smoked . Thus , concern about the health hazards of weight loss and variation may not be applicable to otherwise healthy people Importance Previous studies have shown a U- or J-shaped association of body mass index ( BMI ) or change in BMI with coronary heart disease ( CHD ) among middle-aged and elderly adults . However , whether a similar association exists among young adults is unclear . Objective To determine whether an association exists between BMI or BMI change with CHD among young adults . Design , Setting , and Participants This population -based longitudinal study used data obtained by the Korean National Health Insurance Service from 2002 to 2015 . The study population comprised 2 611 450 men and women aged between 20 and 39 years who underwent 2 health examinations , the first between 2002 and 2003 and the second between 2004 and 2005 . Exposures World Health Organization Western Pacific Region guideline BMI categories of underweight , normal weight , overweight , obese grade 1 , and obese grade 2 derived during the first health examination and change in BMI calculated during the second health examination . Main Outcomes and Measures Body mass index ( calculated as weight in kilograms divided by height in meters squared ) . Absolute risks ( ARs ) , adjusted hazard ratios ( aHRs ) , and 95 % CIs for acute myocardial infa rct ion or CHD during follow-up from 2006 to 2015 . Results Data from 1 802 408 men with a mean ( SD ) age of 35.1 ( 4.8 ) years and 809 042 women with a mean ( SD ) age of 32.5 ( 6.3 ) years were included . The mean ( SD ) BMI was 23.2 ( 3.2 ) for the total population , 24.0 ( 3.0 ) for men , and 21.4 ( 2.9 ) for women . Compared with normal weight men , overweight ( AR , 1.38 % ; aHR , 1.18 [ 95 % CI , 1.14 - 1.22 ] ) , obese grade 1 ( AR , 1.86 % ; aHR , 1.45 [ 95 % CI , 1.41 - 1.50 ] ) , and obese grade 2 ( AR , 2.69 % ; aHR , 1.97 [ 95 % CI , 1.86 - 2.08 ] ) men had an increased risk of CHD ( P < .001 for trend ) . Similarly , compared with normal weight women , overweight ( AR , 0.77 % ; aHR , 1.34 [ 95 % CI , 1.24 - 1.46 ] ) , obese grade 1 ( AR , 0.95 % ; aHR , 1.52 [ 95 % CI , 1.39 - 1.66 ] ) , and obese grade 2 ( AR , 1.01 % ; aHR , 1.64 [ 95 % CI , 1.34 - 2.01 ] ) women had an increased risk of CHD ( P < .001 for trend ) . Compared with participants who maintained their weight at normal levels , those who became obese had elevated CHD risk among men ( 0.35 % increase in AR ; aHR , 1.35 [ 95 % CI , 1.17 - 1.55 ] ) and women ( 0.13 % increase in AR ; aHR , 1.31 [ 95 % CI , 0.95 - 1.82 ] ) . Weight loss to normal levels among obese participants was associated with reduced CHD risk for men ( 0.58 % decrease in AR ; aHR , 0.77 [ 95 % CI , 0.64 - 0.94 ] ) and women ( 0.57 % decrease in AR ; aHR , 0.66 [ 95 % CI , 0.45 - 0.98 ] ) . Conclusions and Relevance Obesity and weight gain were associated with elevated risk of CHD among young adults in this study . Studies that prospect ively determine the association between weight change and CHD risk are needed to vali date these findings Objective : To investigate the association between weight change in older adults and mortality in a multiethnic population . Methods : We performed a prospect i ve analysis using data on weight change between the baseline ( 1993–1996 ) and the 10-year follow-up ( 2003–2007 ) surveys in relation to subsequent mortality among 63 040 participants in the Multiethnic Cohort Study in Hawaii and California . The participants were African American , Native Hawaiian , Japanese American , Latino and white , aged 45–75 years at baseline , and did not report heart disease or cancer at either survey . Results : During an average of 7.3 years of follow-up after the 10-year survey , 6623 deaths were identified . Compared with individuals whose weight remained stable ( ±2.5 kg ) , those who lost weight and those with the highest weight gain ( > 10 kg ) were at increased risk of all-cause mortality , with the risks greater for the weight loss ( hazard ratios ( HR ) : 2.86 ; 95 % confidence interval ( 95 % CI ) : 2.62–3.11 for > 10 kg ) than the weight-gain group ( HR : 1.25 ; 95 % CI : 1.11–1.41 for > 10 kg ) , thus result ing in a reverse J-shaped curve . Japanese Americans and Latinos had stronger associations of weight loss > 10 kg with mortality than did African Americans , Native Hawaiians and whites . The increase in risk with weight gain > 10 kg was greater for older ( ⩾55 years at baseline ) than younger individuals , whereas the increase in mortality associated with weight loss was greater for the normal weight ( < 25 kg m−2 at baseline ) participants and never smokers , compared with overweight/obese persons and current smokers , respectively . Conclusions : Our findings confirm the association between weight change and a higher mortality in a healthy , multiethnic population , with higher risks for weight loss than weight gain . On the basis of these observations , public health recommendation should focus on the prevention of weight loss , as well as weight stability within the non-obese range , for middle-aged and older adults |
13,586 | 16,857,779 | We concluded that parenting programmes can be effective in reducing or preventing substance use .
The most effective appeared to be those that shared an emphasis on active parental involvement and on developing skills in social competence , self-regulation and parenting . | We conducted a systematic review of controlled studies of parenting programmes to prevent tobacco , alcohol or drug abuse in children < 18 . | OBJECTIVE To evaluate the effect of the middle and junior high school Drug Abuse Resistance Education ( D.A.R.E. ) and D.A.R.E. Plus programs on drug use and violence . DESIGN R and omized controlled trial of 24 schools , with 3 conditions : D.A.R.E. only , D.A.R.E. Plus , and delayed program control . SETTING Schools and neighborhoods , primarily in Minneapolis-St Paul . PARTICIPANTS All seventh- grade students in 24 schools in the academic year 1999 - 2000 ( N = 6237 at baseline , 67.3 % were white , and there was 84.0 % retention at final follow-up ) . INTERVENTIONS The middle and junior high school D.A.R.E. curriculum in the 16 schools that received D.A.R.E. only and D.A.R.E. Plus . In the 8 schoolts that received D.A.R.E. Plus , additional components included a peer-led parental involvement classroom program called " On the VERGE , " youth-led extracurricular activities , community adult action teams , and postcard mailings to parents . The interventions were implemented during 2 school years , when the cohort was in the seventh and eighth grade s. MAIN OUTCOME MEASURES Self-reported tobacco , alcohol , and marijuana use ; multidrug use ; violence ; and victimization , assessed at the beginning and end of seventh grade and at the end of eighth grade . Growth curve analytic methods were used to assess changes over time by condition . RESULTS There were no significant differences between D.A.R.E. only and the controls ; significant differences among boys between D.A.R.E. Plus and controls for tobacco , alcohol , and multidrug use and victimization ; significant differences among boys between D.A.R.E. Plus and D.A.R.E. only in tobacco use and violence ; and no significant behavioral differences among girls . CONCLUSION D.A.R.E. Plus significantly enhanced the effectiveness of the D.A.R.E. curriculum among boys and was more effective than the delayed program controls , underscoring the potential for multiyear , multicomponent prevention programs and demonstrating sex differences in response to intervention programs This article review s major risk factors for cigarette smoking , alcohol , and other drug abuse and promising community-based approaches to primary prevention . In a longitudinal experimental study , 8 representative Kansas City communities were assigned r and omly to program ( school , parent , mass media , and community organization ) and control ( mass media and community organization only ) conditions . Programs were delivered at either 6th or 7th grade , and panels were followed through Grade 9 or 10 . The primary findings were ( a ) significant reductions at 3 years in tobacco and marijuana use and ( b ) equivalent reductions for youth at different levels of risk . This study provides evidence that a comprehensive community program-based approach can prevent the onset of substance abuse and that the benefits are experienced equally by youth at high and low risk Abstract Preparing for the Drug-Free Years ( PDFY ) is a curriculum design ed to help parents learn skills to consistently communicate clear norms against adolescent substance use , effectively and proactively manage their families , reduce family conflict , and help their children learn skills to resist antisocial peer influences . This study examined the effects of PDFY on the trajectories of these factors , as well as on the trajectory of alcohol use from early to mid adolescence . The sample consisted of 424 rural families of sixth grade rs from schools r and omly assigned to an intervention or a control condition . Data were collected from both parents and students at pretest , posttest , and 1- , 2- and 3 $ $ \frac{1}{2}$$ -year follow-ups . Latent growth models were examined . PDFY significantly reduced the growth of alcohol use and improved parent norms regarding adolescent alcohol use over time . Implication s for prevention and evaluation are discussed OBJECTIVE To examine the long-term effects of an intervention combining teacher training , parent education , and social competence training for children during the elementary grade s on adolescent health-risk behaviors at age 18 years . DESIGN Nonr and omized controlled trial with follow-up 6 years after intervention . SETTING Public elementary schools serving high-crime areas in Seattle , Wash. PARTICIPANTS Of the fifth- grade students enrolled in participating schools , 643 ( 76 % ) were given written parental consent for the longitudinal study and 598 ( 93 % ) were followed up and interviewed at age 18 years . INTERVENTIONS A full intervention provided in grade s 1 through 6 of 5 days of in-service training for teachers each intervention year , developmentally appropriate parenting classes offered to parents when children were in grade s 1 through 3 and 5 through 6 , and developmentally adjusted social competence training for children in grade s 1 and 6 . A late intervention , provided in grade s 5 and 6 only , paralleled the full intervention at these grade s. MAIN OUTCOME MEASURES Self-reported violent and nonviolent crime , substance use , sexual activity , pregnancy , bonding to school , school achievement , grade repetition and school dropout , suspension and /or expulsion , and school misbehavior ; delinquency charges from court records ; grade point average ; California Achievement Test scores : and disciplinary action reports from school records . RESULTS Fewer students receiving full intervention than control students reported violent delinquent acts ( 48.3 % vs 59.7 % ; P=.04 ) , heavy drinking ( 15.4 % vs 25.6 % ; P=.04 ) , sexual intercourse ( 72.1 % vs 83.0 % ; P=.02 ) , having multiple sex partners ( 49.7 % vs 61.5 % ; P=.04 ) , and pregnancy or causing pregnancy ( 17.1 % vs 26.4 % ; P=.06 ) by age 18 years . The full intervention student group reported more commitment ( P=.03 ) and attachment ( P=.006 ) to school , better academic achievement ( P=.01 ) , and less school misbehavior ( P=.02 ) than control students . Late intervention in grade s 5 and 6 only did not significantly affect health-risk behaviors in adolescence . CONCLUSIONS A package of interventions with teachers , parents , and children provided throughout the elementary grade s can have enduring effects in reducing violent behavior , heavy drinking , and sexual intercourse by age 18 years among multiethnic urban children . Results are consistent with the theoretical model guiding the intervention and support efforts to reduce health-risk behaviors through universal interventions in selected communities or schools serving high-crime neighborhoods In this article , we examine the impact of two universal , grade 1 preventive interventions on the onset of tobacco smoking as assessed in early adolescence . The classroom-centered ( CC ) intervention was design ed to reduce the risk for tobacco smoking by enhancing teachers ' behavior management skills in first grade and , thereby , reducing child attention problems and aggressive and shy behavior-known risk behaviors for later substance use . The family-school partnership ( FSP ) intervention targeted these early risk behaviors via improvements in parent-teacher communication and parents ' child behavior management strategies . A cohort of 678 urban , predominately African-American , public school students were r and omly assigned to one of three Grade 1 classrooms at entrance to primary school ( age 6 ) . One classroom featured the CC intervention , a second the FSP intervention , and the third served as a control classroom . Six years later , 81 % of the students completed audio computer-assisted self-interviews . Relative to controls , a modest attenuation in the risk of smoking initiation was found for students who had been assigned to either the CC or FSP intervention classrooms ( 26 % versus 33 % ) ( adjusted relative risk for CC/control contrast=0.57 , 95 % confidence interval ( CI ) , 0.34 - 0.96 ; adjusted relative risk for FSP/control contrast=0.69 , 95 % CI , 0.50 - 0.97 ) . Results lend support to targeting the early antecedent risk behaviors for tobacco smoking This study evaluated the substance initiation effects of an intervention combining family and school-based competency-training intervention components . Thirty-six rural schools were r and omly assigned to 1 of 3 conditions : ( a ) the classroom-based Life Skills Training ( LST ) and the Strengthening Families Program : For Parents and Children 10 - 14 , ( b ) LST only , or ( c ) a control condition . Outcomes were examined 1 year after the intervention posttest , using a substance initiation index ( SII ) measuring lifetime use of alcohol , cigarettes , and marijuana and by rates of each individual substance . Planned intervention-control contrasts showed significant effects for both the combined and LST-only interventions on the SII and on marijuana initiation . Relative reduction rates for alcohol initiation were 30.0 % for the combined intervention and 4.1 % for LST only Project Northl and was a r and omized trial to reduce alcohol use among adolescents in 24 school districts in northeastern Minnesota . Phase 1 ( 1991 - 1994 ) , when the targeted cohort was in grade s 6 - 8 , included school curricula , parent involvement , peer leadership and community task forces . The Interim Phase ( 1994 - 1996 ) involved minimal intervention . Phase 2 ( 1996 - 1998 ) , when the cohort was in grade s 11 and 12 , included a classroom curriculum , parent education , print media , youth development and community organizing . Outcomes of these interventions were assessed by annual student surveys from 1991 to 1998 , alcohol purchase attempts by young-looking buyers in 1991 , 1994 and 1998 , and parent telephone surveys in 1996 and 1998 . Growth curve analysis was used to examine the student survey data over time . Project Northl and was most successful when the students were young adolescents . The lack of intervention in the Interim Phase when the students were in grade s 9 and 10 had a significant and negative impact on alcohol use . The intervention used with the high school students as those in grade s 11 and 12 made a positive impact on their tendency to use alcohol use , binge drinking and ability to obtain alcohol . There was no impact in Phase 2 on other student-level behavioral and psychosocial factors . Developmentally appropriate , multi-component , community-wide programs throughout adolescence appear to be needed to reduce alcohol use In autumn 1995 The Norwegian Cancer Society in cooperation with The Research Center for Health Promotion , University of Bergen started a study of school-based interventions aim ing at preventing smoking among pupils in Norwegian secondary schools . The study comprised a nationwide sample of 4441 students at 99 schools ( 195 classes ) . This panel of students is followed through annual data collection s till they graduate in spring 1997 . Written consensus from students and parents was obtained from 95 % . Schools were systematic ally allocated to one of four groups : Group A , control ; Group B , intervention , containing classroom program , involvement of parents and teacher courses ; Group C , like B , but without teacher courses ; Group D , like B , but without parental involvement . Baseline data were collected by question naires administered in class in November 1994 and the first follow-up survey was carried out in May 1995 . At follow-up the proportion of smokers had increased by 8.3 percentage points in Group A ( control ) and by 1.9 percentage points in Group B ( most extensive intervention ) . As expected , the recruitment of smokers was higher in Groups C and D than in the ideal intervention , but lower than in the control group . Effects of the most extensive program among subgroups of students were examined by comparing Groups A and B. Students are categorized as high risk or low risk based on scores on scales measuring sensation seeking , physical maturity , antisocial behavior and parental smoking . The effect of the program on recruitment of smokers seems to have been at least as strong or even stronger among ' high-risk ' students than among other students Objective : To evaluate Smoke-free Kids , a new home based programme to assist parents who smoke in socialising their children against smoking . Design : Two year r and omised controlled trial . Participants : At baseline , 887 adult smokers who had an abstinent child in the third grade ( ages 7–8 years ) ; 671 adults and children were retained through the 24 month follow up . Intervention : Programme modules , newsletters , incentives , support calls . Outcomes : Anti-smoking socialisation ; susceptibility to smoking . Results : Of 327 parents r and omised to treatment , 210 obtained adequate treatment by using at least three of five core modules . Programme efficacy analyses , which compared these parents with controls ( n = 344 ) , showed that exposure to adequate treatment predicted significantly higher levels in nearly all categories of anti-smoking socialisation three months post-intervention . Two years post-baseline , children of parents who reported adequate treatment scored significantly higher than controls on attributes that reduce susceptibility to smoking , and they scored significantly lower than controls on attributes that raise susceptibility to smoking . Programme effectiveness analyses compared all parents r and omised to treatment ( n = 327 ) with controls ( n = 344 ) . Treatment effects were evident for several socialisation outcomes ; however , these effects were smaller and less consistent than those from the efficacy analyses . Similarly , although treated children scored higher than controls on attributes that reduce susceptibility and lower than controls on attributes that raise susceptibility , several of these between-group differences were not significant . Conclusions : Given adequate exposure to the Smoke-free Kids programme , significant beneficial effects were observed on anti-smoking socialisation in households where parents smoke cigarettes , and significant beneficial effects were observed on children ’s susceptibility to smoking after two years . Improving programme acceptance and utilisation is necessary before programme effectiveness can be demonstrated This study examined the 1-year follow-up effects of the STARS ( Start Taking Alcohol Risks Seriously ) for Families program , a 2-year preventive intervention based on a stage of acquisition model , and consisting of nurse consultations and parent material s. A r and omized controlled trial was conducted , with participants receiving either the intervention or a minimal intervention control . Participants included a cohort of 650 sixth- grade students from two urban middle schools-one magnet ( bused ) and one neighborhood . Trained project staff administered question naires to students following a st and ardized protocol in the schools . For the magnet school sample , significantly fewer intervention students ( 5 % ) were planning to drink in the next 6 months than control students ( 18 % ) , chi2 = 11.53 , 1 d.f . , P = 0.001 . Magnet school intervention students also had less intentions to drink in the future , greater motivation to avoid drinking and less total alcohol risk than control students , Ps < 0.05 . For the neighborhood school , intervention students ( m = 7.90 , SD = 1.87 ) had less total alcohol risk than control students ( m = 8.42 , SD = 1.83 ) , F(1,205 ) = 4.09 , P = 0.04 . These findings suggest that a brief , stage and risk/protective factor tailored program holds promise for reducing risk for alcohol use among urban school youth 1 year after intervention , and has the unique advantage of greater ' transportability ' over classroom-based prevention programs OBJECTIVE Systematic evaluation of theoretically and empirically based family programs to prevent adolescent alcohol use/misuse is limited . Data presented here are from a longitudinal study evaluating a home-based universal adolescent alcohol use prevention program . The intervention was design ed to enhance protective factors and minimize risk factors identified as influencing adolescent alcohol use . METHOD A r and omized pretest/posttest repeated measures design was used . Adolescents ( N = 428 ; 54 % females , 86 % European American ) and their parents were recruited from three Midwestern school districts . Families were r and omly assigned to either a three-session family intervention or a no-intervention control condition . Pretest data collection and the intervention occurred when the adolescents were in fourth grade , and a booster intervention was given in seventh grade . Posttest data collection was completed each year for 4 years in the classroom for adolescents . RESULTS The intervention was associated with a reduction in alcohol use ( F = 5.16 , 4/421 df , p < .001 ) and misuse ( F = 3.08 , 4/421 df , p < .05 ) for those adolescents in the intervention condition who were not using alcohol prior to the initiation of the program , but not for those who were using alcohol before initiation of the program . CONCLUSIONS The results support the possible effectiveness of the family intervention as a universal prevention program for decreasing initiation of alcohol use and subsequent misuse for the majority of adolescents who do not report prior drinking . However , additional intervention approaches appear necessary for adolescents who have already used alcohol This study examined the long-term substance use outcomes of 2 brief interventions design ed for general population families of young adolescents . Thirty-three public schools were r and omly assigned to 3 conditions : the 5-session Preparing for the Drug Free Years Program , the 7-session Iowa Strengthening Families Program , and a minimal contact control condition . The pretest involved 667 6th grade rs and their families . Assessment s included multiple measures of initiation and current use of alcohol , tobacco , and marijuana . Pretest data were collected in the 6th grade and the reported follow-up data were collected in the 10th grade . Significant intervention-control differences in initiation and current use were found for both interventions . It is concluded that brief family skills-training interventions design ed for general population s have the potential to reduce adolescent substance use and thus have important public health implication |
13,587 | 29,637,551 | A large proportion of the overall public health burden of epilepsy is attributable to preventable causes . | Among the causes of epilepsy are several that are currently preventable .
In this review , we summarize the public health burden of epilepsy arising from such causes and suggest priorities for primary epilepsy prevention . | BACKGROUND Taenia solium neurocysticercosis ( NCC ) has been documented as one of the major causes of epilepsy in developing countries . However , method ological limitations have hindered the evaluation of the epidemiological relationship between cysticercosis and epilepsy at the community level . METHODS We used the WHO protocol for epidemiological evaluation of neurological disorders to conduct a door-to-door survey among 2723 residents of San Pablo del Lago , an Ecuadorean rural community in which T. solium taeniasis/cysticercosis was known to be endemic . The WHO protocol was complemented by neuroimaging and immunological tests to confirm the diagnosis of this infection . RESULTS In all 31 people suffering from active epilepsy were detected ( prevalence 11.4 per 1000 , 95 % CI:7.7 - 15.4 ) ; 26 agreed to undergo a computer tomography ( CT ) examination , and 28 agreed to have blood drawn for serodiagnosis . Fourteen of the 26 ( 53.8 % ) had CT changes compatible with NCC and six of the 28 ( 21.4 % ) tested positive in the enzyme-linked immunoelectro-transfer blot ( EITB ) assay . In a seizure-free r and om sample of this population , 17 of 118 ( 144 per 1000 ) subjects examined by CT and 10 out of 96 ( 104 per 1000 ) examined by EITB had evidence of this infection . The differences between the epilepsy group and the r and om sample of the population were statistically significant ( OR = 6.93 , 95 % CI : 2.7 - 17.5 , P < 0.001 ) for CT diagnosis , but not for EITB results ( OR = 2.75 , 95 % CI : 0.8 - 7.1 , P > 0.12 , NS ) . CONCLUSIONS These findings confirm that T. solium NCC is a significant cause of epilepsy at the community level in And ean villages of Ecuador . It is important to initiate effective public health interventions to eliminate this infection , which may be responsible for at least half of the cases of reported epilepsy in Ecuador OBJECTIVE Neurologic diseases such as stroke are risk factors for new-onset epilepsy in older adults . Recent evidence suggests that psychiatric disorders independently predict epilepsy in older male veterans . Our aim was to examine the relationship between these disorders in a population -based study of older adults that also included women and minorities . METHODS We used a national 5 % r and om sample of 2005 Medicare beneficiaries including all 50 US states and Washington , DC . Beneficiaries were 65 years of age or older , with continuous Medicare Part A and Part B coverage and not in managed care plans . Epilepsy cases were identified from cl aims for physician visits , hospitalizations , and outpatient procedures . We used logistic regressions for the overall sample and stratified by gender to determine whether risk of new-onset epilepsy was associated with prior history of psychiatric ( i.e. , depression , psychosis , bipolar disorder , schizophrenia , posttraumatic stress disorder ( PTSD ) , adjustment disorder , and substance abuse/dependence ) and neurologic conditions ( i.e. , cerebrovascular disease , dementia , traumatic brain injury , brain tumor , metastatic cancer ) . RESULTS Preexisting psychiatric disorders were significantly associated with new-onset epilepsy in the study population as were the neurologic conditions evaluated . Five of the seven psychiatric disorders examined were independently associated with new-onset epilepsy ; substance abuse , psychosis , bipolar disorder , schizophrenia , and depression . Gender interaction effects were found for substance abuse/dependence and brain tumors . SIGNIFICANCE Both neurologic and psychiatric factors significantly predicted new-onset epilepsy in a population -based sample of male and female older adults . These results support earlier findings and extend the underst and ing of risk models for new-onset epilepsy in broader older adult population Summary Background The prevalence of epilepsy in sub-Saharan Africa seems to be higher than in other parts of the world , but estimates vary substantially for unknown reasons . We assessed the prevalence and risk factors of active convulsive epilepsy across five centres in this region . Methods We did large population -based cross-sectional and case-control studies in five Health and Demographic Surveillance System centres : Kilifi , Kenya ( Dec 3 , 2007–July 31 , 2008 ) ; Agincourt , South Africa ( Aug 4 , 2008–Feb 27 , 2009 ) ; Iganga-Mayuge , Ug and a ( Feb 2 , 2009–Oct 30 , 2009 ) ; Ifakara , Tanzania ( May 4 , 2009–Dec 31 , 2009 ) ; and Kintampo , Ghana ( Aug 2 , 2010–April 29 , 2011 ) . We used a three-stage screening process to identify people with active convulsive epilepsy . Prevalence was estimated as the ratio of confirmed cases to the population screened and was adjusted for sensitivity and attrition between stages . For each case , an age-matched control individual was r and omly selected from the relevant centre 's census data base . Fieldworkers masked to the status of the person they were interviewing administered question naires to individuals with active convulsive epilepsy and control individuals to assess sociodemographic variables and historical risk factors ( perinatal events , head injuries , and diet ) . Blood sample s were taken from a r and omly selected subgroup of 300 participants with epilepsy and 300 control individuals from each centre and were screened for antibodies to Toxocara canis , Toxoplasma gondii , Onchocerca volvulus , Plasmodium falciparum , Taenia solium , and HIV . We estimated odds ratios ( ORs ) with logistic regression , adjusted for age , sex , education , employment , and marital status . Results 586 607 residents in the study areas were screened in stage one , of whom 1711 were diagnosed as having active convulsive epilepsy . Prevalence adjusted for attrition and sensitivity varied between sites : 7·8 per 1000 people ( 95 % CI 7·5–8·2 ) in Kilifi , 7·0 ( 6·2–7·4 ) in Agincourt , 10·3 ( 9·5–11·1 ) in Iganga-Mayuge , 14·8 ( 13·8–15·4 ) in Ifakara , and 10·1 ( 9·5–10·7 ) in Kintampo . The 1711 individuals with the disorder and 2032 control individuals were given question naires . In children ( aged < 18 years ) , the greatest relative increases in prevalence were associated with difficulties feeding , crying , or breathing after birth ( OR 10·23 , 95 % CI 5·85–17·88 ; p<0·0001 ) ; abnormal antenatal periods ( 2·15 , 1·53–3·02 ; p<0·0001 ) ; and head injury ( 1·97 , 1·28–3·03 ; p=0·002 ) . In adults ( aged ≥18 years ) , the disorder was significantly associated with admission to hospital with malaria or fever ( 2·28 , 1·06–4·92 ; p=0·036 ) , exposure to T canis ( 1·74 , 1·27–2·40 ; p=0·0006 ) , exposure to T gondii ( 1·39 , 1·05–1·84 ; p=0·021 ) , and exposure to O volvulus ( 2·23 , 1·56–3·19 ; p<0·0001 ) . Hypertension ( 2·13 , 1·08–4·20 ; p=0·029 ) and exposure to T solium ( 7·03 , 2·06–24·00 ; p=0·002 ) were risk factors for adult-onset disease . Interpretation The prevalence of active convulsive epilepsy varies in sub-Saharan Africa and that the variation is probably a result of differences in risk factors . Programmes to control parasitic diseases and interventions to improve antenatal and perinatal care could substantially reduce the prevalence of epilepsy in this region . Funding Wellcome Trust , University of the Witwatersr and , and South African Medical Research Council OBJECTIVE To determine age-specific incidence and cumulative incidence of epilepsy in a well-defined cohort of elderly people , and to examine how rates of epilepsy are modified by sex , race , stroke , dementia , head injury , and depression . METHODS The authors examined data from a reconstructed cohort based on 1919 community-dwelling volunteers , followed as part of a large ongoing prospect i ve aging study . RESULTS Age-specific incidence was 10.6 ( per 100,000 person-years ) between ages 45 and 59 , 25.8 between ages 60 and 74 , and 101.1 between ages 75 and 89 . Cumulative incidence was 0.15 % from age 45 to age 60 , 0.38 % to age 70 , 1.01 % to age 80 , and 1.47 % to age 90 . In addition , the difference in cumulative incidence among African-American subjects approached statistical significance ( 57.6/100,000 person-years versus 26.1 in Caucasian , p=0.10 ) , and the difference in incidence among subjects reporting a history of stroke was significantly elevated ( p=0.029 ) . Incidence of epilepsy was not statistically elevated among males , those with dementia , or individuals reporting a history of head injury or treatment for depression . Among " healthy " subjects without history of stroke , head injury , or dementia , we observed a cumulative risk of epilepsy with onset after age 60 of only 1.1 % . CONCLUSIONS The incidence of epilepsy was low in this relatively healthy cohort of elderly people , especially among subjects without known risk factors . In this study we identified African-American race as a risk factor in the elderly for epilepsy independent of stroke BACKGROUND The aim of the study was to estimate the prevalence of different types of epilepsy and their possible risk factors in the region of the Assiut Governorate/Egypt . MATERIAL AND METHODS A community based study with r and om sampling of 7 districts , involving 6498 inhabitants . Out of this sample , 578 dropped out leaving 3066 males ( 51.8 % ) and 2854 females ( 48.2 % ) . There were 3660 ( 61.8 % ) urban residents and 2260 ( 38.2 % ) from the rural community . Patients were evaluated using a screening question naire for epilepsy , and then referred to the hospital to be re-evaluated by a qualified neurologist and with electroencephalography ( EEG ) and computed tomography of the brain ( CT ) . RESULTS Seventy-five cases were diagnosed with epilepsy giving an overall the crude lifetime prevalence rate ( CPR ) for epilepsy of 12.67/1000 ( 95 % CI : 9.8 - 15.54 ) . The active prevalence rate was 9.3/1000 and the incidence rate was 1.5/1000 ( 95 % confidence interval : 0.53 - 2.51 ) . Fifty-six cases ( 75 % ) had idiopathic epilepsy ( CPR 9.5/1000 ) . Symptomatic epilepsy was recorded in 19 ( 25 % ) cases ( CPR 3.2/1000 ) . Generalized seizures were more common ( CPR 6.75/1000 ) than partial seizures ( CPR 2.5/1000 ) . The prevalence rate of partial seizures evolving to secondary generalization was 0.84/1000 while simple partial and complex partial seizures had CPR 1.4/1000 and 0.34/1000 , respectively . The CPR of mixed seizures was 0.17/1000 . Epilepsy was slightly but not significantly more common among males than females ( CPR of 14.4 and 10.9 per 1000 population , respectively ) . The CPR was higher in rural than urban population s ( 17.7/1000 , with 95 % CI 12.2 - 23.18 and 9.56/1000 , with 95 % CI : 6.39 - 12.7 , respectively ) and in the illiterate group than the literate population ( 12.02/1000 and 9.94/1000 , respectively ) . The highest prevalence rate was recorded in the early and late childhood period ( 69.78/100,000 and 43.78/100,000 , respectively ) . Prenatal insults and infection represented major causes of symptomatic epilepsy . CONCLUSIONS We found a high prevalence rate of epilepsy ( comparable with that in other Arabic and European countries ) in our community particularly among children and teenagers . Overall the prevalence was higher in the rural than in the urban population . A family history of epilepsy , prenatal insults , and infection represented major risk factors of symptomatic epilepsy BACKGROUND Taeniasis and cysticercosis are major causes of seizures and epilepsy . Infection by the causative parasite Taenia solium requires transmission between humans and pigs . The disease is considered to be eradicable , but data on attempts at regional elimination are lacking . We conducted a three-phase control program in Tumbes , Peru , to determine whether regional elimination would be feasible . METHODS We systematic ally tested and compared elimination strategies to show the feasibility of interrupting the transmission of T. solium infection in a region of highly endemic disease in Peru . In phase 1 , we assessed the effectiveness and feasibility of six intervention strategies that involved screening of humans and pigs , antiparasitic treatment , prevention education , and pig replacement in 42 villages . In phase 2 , we compared mass treatment with mass screening ( each either with or without vaccination of pigs ) in 17 villages . In phase 3 , we implemented the final strategy of mass treatment of humans along with the mass treatment and vaccination of pigs in the entire rural region of Tumbes ( 107 villages comprising 81,170 people and 55,638 pigs ) . The effect of the intervention was measured after phases 2 and 3 with the use of detailed necropsy to detect pigs with live , nondegenerated cysts capable of causing new infection . The necropsy sampling was weighted in that we preferentially included more sample s from seropositive pigs than from seronegative pigs . RESULTS Only two of the strategies implemented in phase 1 result ed in limited control over the transmission of T. solium infection , which highlighted the need to intensify the subsequent strategies . After the strategies in phase 2 were implemented , no cyst that was capable of further transmission of T. solium infection was found among 658 sample d pigs . One year later , without further intervention , 7 of 310 sample d pigs had live , nondegenerated cysts , but no infected pig was found in 11 of 17 villages , including all the villages in which mass antiparasitic treatment plus vaccination was implemented . After the final strategy was implemented in phase 3 , a total of 3 of 342 pigs had live , nondegenerated cysts , but no infected pig was found in 105 of 107 villages . CONCLUSIONS We showed that the transmission of T. solium infection was interrupted on a regional scale in a highly endemic region in Peru . ( Funded by the Bill and Melinda Gates Foundation and others . ) |
13,588 | 27,670,126 | There is low certainty of the usefulness of MAL-PDT ( red light ) or ALA-PDT ( blue light ) as st and ard therapies for people with moderate to severe acne . | BACKGROUND Acne vulgaris is a very common skin problem that presents with blackheads , whiteheads , and inflamed spots .
It frequently results in physical scarring and may cause psychological distress .
The use of oral and topical treatments can be limited in some people due to ineffectiveness , inconvenience , poor tolerability or side-effects .
Some studies have suggested promising results for light therapies .
OBJECTIVES To explore the effects of light treatment of different wavelengths for acne . | BACKGROUND Acne treatments using laser and light devices have been reported to have varying degrees of efficacy . However , there has been no study of treatment of acne using a dual mode ( quasi-long pulse and Q-switched mode ) 1064-nm Nd : YAG laser assisted with a topically applied carbon suspension . OBJECTIVE To evaluate the clinical efficacy , safety , and histological changes of new laser treatment method for acne vulgaris . METHODS Twenty-two patients received 3 sessions of quasi-long pulse and Q-switched Nd : YAG laser treatment assisted with a topically applied carbon suspension at 2-week intervals in a r and omized split face manner . RESULTS At the final visit , the inflammatory acne lesions were reduced on the laser-treated side by 58.6 % ( P < .001 ) , but increased on the untreated side by 5 % . The noninflammatory acne lesions were reduced on the laser-treated side by 52.4 % ( P < .001 ) . Sebum output reduction , inflammatory cell and cytokine reductions , a decrease of the thickness of a perifollicular stratum corneum and a full epithelium , and skin rejuvenation effect were found . The histopathologic examination of the acne lesions showed decreased inflammation and immunostaining intensity for interleukin 8 , matrix metalloproteinase-9 , toll-like receptor-2 , and nuclear factor kappa B , and tumor necrosis factor alpha was reduced significantly . No severe adverse reactions were reported . All patients reported mild transient erythema that disappeared in a few hours . LIMITATIONS The number of subjects studied was small . CONCLUSIONS This laser treatment was rapid and effective for treating not only the inflammatory but also the noninflammatory acne lesions when compared with the control side . The histopathologic findings correlated well with the clinical acne grade and treatment response . This novel laser treatment appears to be safe and effective for acne treatment Background / Purpose : Acne vulgaris is a very prevalent skin disorder and remains a main problem in practice . Recently , phototherapy with various light spectrums for acne has been used . There are some evidence s that low-level laser therapy ( LLLT ) has beneficial effect in the treatment of acne lesions . In this study , two different wavelengths of LLLT ( 630 and 890 nm ) were evaluated in treatment of acne vulgaris . Material s and Methods : This study was a single-blind r and omized clinical trial . Patients with mild to moderate acne vulgaris and age above 18 years and included were treated with red LLLT ( 630 nm ) and infrared LLLT ( 890 nm ) on the right and left sides of the face respectively , twice in a week for 12 sessions , and clinical ly assessed at baseline and weeks 2 , 4 , 6 , and 8 . Results : Twenty-eight patients were participated in this study . Ten weeks after treatment acne lesion were significantly decreased in the side treated by 630 nm LLLT ( 27.7±12.7 to 6.3±1.9 ) ( P<0.001 ) , but this decrease was not significant in the site treated by 890 nm LLLT ( 26.9±12.4 to 22.2±8.5 ) ( P>0.05 ) . Conclusion : Red wavelength is safe and effective to be used to treat acne vulgaris by LLLT compared to infrared wavelength BACKGROUND Acne patients who fail to respond to conventional treatments have been treated with isotretinoin , an effective treatment coming under strict regulation due to the risk of significant side effects . Photodynamic therapy ( PDT ) may be a viable alternative treatment for recalcitrant acne of various types and levels of severity . OBJECTIVE To determine the safety and efficacy of combination PDT with topical 5-aminolevulinic acid ( ALA ) and activation by long-pulsed , pulsed dye laser ( LP PDL , 595 nm ) energy with topical therapy in patients with mild to severe acne . METHODS A prospect i ve , controlled pilot , proof-of-principle study of 19 consecutive patients ( aged 16 - 47 years , Fitzpatrick skin types I-VI ) with mild to severe cystic , inflammatory , or comedonal acne of the face was conducted . All patients had failed conventional therapy , including oral antibiotics , topical treatments , hormonal therapy , laser procedures ( without ALA ) , and /or oral isotretinoin . Fifteen patients were treated with ALA PDT and 4 patients served as controls ; all were continued on topical medications . Patients undergoing PDT were initially r and omized to receive either blue light or laser energy . Because recrudescence occurred in 1 patient while undergoing multiple treatments with ALA and blue light , all subsequent patients were treated with ALA and laser energy . The total number of patients treated with LP PDL-mediated ALA PDT was 14 . ALA was applied for a short 45-minute incubation followed by 1 minimally overlapping pass with the LP PDL ( 595 nm , 7.0 - 7.5 J/cm2 fluence , 10-ms pulse duration , 10-mm spot size , and dynamic cooling spray of 30 ms with a 30-ms delay ) . Patients treated with conventional therapy ( oral antibiotics , oral contraceptives , and topical medications ) or laser energy without ALA PDT served as control groups . Patients were followed monthly for up to 13 months . RESULTS Complete clearance was achieved in 100 % ( 14 out of 14 ) patients in the LP PDL PDT-treated group . A mean of 2.9 treatments ( range 1 - 6 ; 2.0 - 3.7 , 95 % CI ; n=14 ) was required to achieve complete clearance for a mean follow-up time of 6.4 months ( range 1 - 13 ; 3.8 - 8.9 95 % CI ; n=14 ) . The patient mean percent lesional clearance rate per treatment was 77 % ( 64%-90 % , 95 % CI ; n=14 ) . Improvement in acne lesions became apparent within 1 to 2 weeks after the first treatment . Clearance in the LP PDL PDT group was superior to control groups . In the LP PDL-only control group ( n=2 ) , the patient mean percent lesional clearance rate per treatment was 32 % without complete clearance after 3 to 4 treatments . In the oral antibiotics , oral contraceptives , and topicals control group ( n=2 ) , the clearance rate per treatment was 20 % , the mean clearance rate per month was 4 % , and complete clearance was not achieved after 6 to 10 months . In the LP PDL-mediated PDT group , treatments were well-tolerated with minimal erythema lasting 1 to 2 days . No cases of crusting , blistering , purpura , scarring , or dyspigmentation occurred . A reduction in the erythema in erythematous acne scars was observed . CONCLUSION For teenage to adult patients with recalcitrant comedonal , inflammatory , or cystic acne of various degrees of severity , ALA PDT with activation by LP PDL appears to be a safe and effective treatment with minimal side effects . LP PDL-mediated PDT may serve as an important alternative to isotretinoin . Cosmetically well-accepted , LP PDL PDT combined with topical therapy is the first PDT modality to achieve complete clearance with long-term follow-up as compared to controls BACKGROUND It has been suggested that cystic acne is rare in women 15 to 44 years of age and infrequent in men . OBJECTIVE To determine the prevalence of acne , we analyzed the primary data from the National Health and Nutrition Examination Survey ( NHANES ) that included a cutaneous examination of a stratified r and om sample of 20,749 noninstitutionalized U.S. residents . METHODS We calculated the prevalence of various disease states based on NHANES primary data and the NHANES population weights . Prevalence estimates and male/female ratios of these estimates were calculated . RESULTS From 1971 to 1974 , the projected prevalence of acne conglobata ( grade IV acne ) for women and men 15 to 44 years of age in the United States was 250,000 and 570,000 , respectively . At the time of examination , an additional 582,000 women and 749,000 men were projected to have moderate acne with cysts and scars . Therefore the prevalence of acne conglobata and acne of at least a moderate degree with cysts and scars was 832,000 for women and 1,319,000 for men 15 to 44 years of age . The male/female ratio for acne with cysts and scars is approximately 1.6:1 . CONCLUSION The NHANES examination data demonstrate that acne with cysts and scars is common in both men and women BACKGROUND Long-pulsed dye laser (LPDL)-assisted photodynamic therapy has been suggested to be superior to laser alone for acne vulgaris but no evidence is available . OBJECTIVE To evaluate the efficacy and safety of LPDL alone versus LPDL in photodynamic therapy with methylaminolevulinic acid ( MAL-LPDL ) for acne vulgaris . METHODS Fifteen patients received a series of 3 full-face LPDL treatments and half-face prelaser MAL treatments ; the latter being r and omly assigned to the left or right side . RESULTS Inflammatory lesions were reduced more on MAL-LPDL-treated than on LPDL-treated sides ( week 4 : 70 % vs 50 % , P = .003 ; week 12 : 80 % vs 67 % , P = .004 ) . Noninflammatory lesions reduced similarly . Patient satisfaction was slightly greater with MAL-LPDL versus LPDL treatments ( scale 0 - 10 : week 4 : 7 vs 6 , P = .034 ; week 12 : 8 vs 7.5 , P = .034 ) . Fluorescence measurements detected photobleaching with MAL-LPDL ( 35.3 % ) and LPDL ( 7.3 % ) treatments ( P < .001 ) . Erythema , edema , and pustular eruptions intensified from MAL incubation . No patients experienced pigment changes or scarring . LIMITATIONS The sample size was limited . The split-face design in this r and omized controlled trial does not allow us to draw conclusions about the efficacy of the LPDL , only about the efficacy of MAL-LPDL compared with LPDL alone . CONCLUSIONS MAL-LPDL is slightly superior to LPDL for the treatment of inflammatory acne Abstract Introduction : The aim was to compare the treatment effectiveness of intense pulsed light ( IPL ) and vacuum versus IPL with placebo for mild to moderate comedonal and inflammatory acne . Patients and methods : We r and omized 180 patients with mild to moderate comedonal and inflammatory acne into three groups : Group A – 60 patients treated with vacuum and IPL , Group V – 60 patients treated with IPL , and Group 0 ( control group ) – 60 patients who received topical treatment with Sebium H2O Micellaire Solution . We evaluated the results using the Leeds revised acne-grading system and Cardiff Acne Disability Index . Results : There was a significant reduction in the number of papules , pustules , and comedones in Groups A and V compared with those in the control group ( p < 0.001 ) with a more rapid decrease of the papules from Group A compared with that from Group V. We found an improvement in the clinical aspect ( p < 0.001 ) when we compared Groups A and V with controls . Patients belonging to Group A were more satisfied compared with those belonging to Group V ( p = 0.004 ) and significantly more satisfied compared with those belonging to Group 0 ( p < 0.001 ) . In conclusion , we consider that both the devices are efficient , the combination of vacuum and IPL representing a therapeutic option for the comedonal acne BACKGROUND Various forms of laser therapy including the pulsed-dye laser ( PDL ) have been reported to reduce acne lesion counts . OBJECTIVE In this study , the benefits and complications when using a 595-nm PDL for the treatment of acne vulgaris were evaluated when comparing a subpurpuric ( low ) fluence level with a purpuric ( high ) fluence level . MATERIAL S AND METHODS This study was a prospect i ve , single-blinded split-face clinical trial . Inclusion criteria included subjects with moderate to severe facial acne . All participants were treated with PDL , with each half of the face receiving either high or low fluence at 3-week intervals for a total of 4 treatments . St and ardized facial photographs were obtained and blindly evaluated . RESULTS Sixty-two subjects were enrolled with a mean age of 22.3 years . Fifty-five patients completed the study . The results showed a significant decrease in lesion counts compared with baseline after all treatments . However , the study did not demonstrate a statistically significant difference between the fluence parameters . The only treatment-related adverse event was temporary hyperpigmentation . CONCLUSION This study demonstrates that PDL is effective in reducing acne lesions using purpuric and subpurpuric fluences . However , there was no statistically significant difference in acne lesion count between the higher and lower fluences BACKGROUND The success rates of conventional treatments to acne vulgaris are limited because of intolerance and resistance . Photodynamic therapy with topical 5-aminolevulinic acid ( ALA ) and red light has been introduced . However , the side effects especially pigmentation are common . OBJECTIVE To study the efficacy and safety of ALA-photodynamic therapy ( PDT ) with 420 - 950 nm intense pulsed light ( IPL ) in Chinese patients with acne vulgaris . METHODS Forty-one patients with moderate to severe facial acne were r and omly assigned to ALA-IPL-PDT group and IPL group . Ten percent topical ALA was applied to patients in the ALA-IPL-PDT group , while placebos were applied to patients in the IPL group . After 1 h occlusion , all patients were illuminated with 420 - 950 nm IPL . The patients in both groups had four treatment sessions with 1-week intervals . One week after each treatment and 4 , 8 , and 12 weeks after four sessions , acne lesion counts and adverse events were observed . RESULTS Twelve weeks after treatments , mean reductions of global lesion counts of ALA-IPL-PDT group and IPL group were 75.2 % and 51.0 % , respectively . Mean reductions of inflammatory and non-inflammatory lesion counts in ALA-IPL-PDT group were ( 83.6 ± 4.1)% and ( 57.5 ± 6.8)% , respectively . No severe adverse events were observed . CONCLUSION ALA-IPL-PDT is an effective treatment for moderate to severe acne vulgaris , and side effects are mild and reversible INTRODUCTION Pulsed dye laser ( PDL ) has been used to treat acne lesions and scar erythema by interrupting superficial vasculature . Salicylic acid chemical peels are employed chiefly due to their lipophilic , comedolytic , and anti-inflammatory properties . Although studies have looked at peels and laser therapy independently in acne management , we examined these treatments in combination . Our primary objective was to evaluate the safety and efficacy of concurrent use of salicylic acid peels with PDL versus salicylic acid peels alone in the treatment of moderate to severe acne vulgaris . METHODS Adult patients with moderate to severe acne were included . Subjects received a total of 3 treatments at 3-week intervals . Per r and omized split-face treatment , at week 0 , one half of the subject 's face was treated with PDL ( 595 nm ) followed by whole face application of a 30 % salicylic acid peel . At weeks 3 and 6 , the treatments were repeated . At 0 and 9 weeks , patients were assessed with the Global Evaluation Acne ( GEA ) scale and Dermatology Life Quality Index ( DLQI ) question naire . RESULTS Nineteen subjects were enrolled , and 18 completed the study . Significant improvement in acne was seen in both the combined ( laser and peel ) and chemical peel alone treatment arms ( P < .0005 and P = .001 ) . Using the GEA scale score , compared to week 0 , the mean difference in acne improvement at week 9 was -1.61 in the combination therapy group versus -1.11 in the peel only group . Based on the GEA scale scoring , a statistically significant greater difference in acne improvement was seen , from week 0 to week 9 , in the combination treatment group compared with the peel only group ( P = .003 ) . CONCLUSION While acne subjects had significant benefit from the salicylic acid peel alone , they experienced greater significant benefit from PDL treatment used in conjunction with salicylic acid peels . The adjunctive utilization of PDL to salicylic acid peel therapy can lead to better outcomes in acne management BACKGROUND Photodynamic therapy ( PDT ) has been proposed as a treatment option for acne vulgaris . The authors have proposed in this work a liposomal delivery for methylene blue ( MB ) for selective acne treatment . OBJECTIVES To evaluate the efficacy and tolerability of liposomes loaded methylene blue ( LMB ) based photodynamic therapy in patients with mild-to-moderate acne vulgaris in a r and omized , controlled and investigator blinded study . MATERIAL S AND METHODS Liposomes loaded methylene blue ( LMB ) was prepared and studied for different pharmaceutical properties and formulated in hydrogel ( MB 0.1 % ) . Permeability and selective sebaceous gl and targeting in mice skin was studied . Gel containing LMB was used for treating 13 patients complaining of mild-moderate acne vulgaris once a week for two weeks . Efficacy evaluation included changes in lesions counts , clinical assessment s of clinical improvement by patients and evaluating dermatologists . Pain and local adverse effects were also evaluated . RESULTS The mechanism of the drug released from liposomes ( both in pH = 5.5 and in pH = 7.2 ) was following zero order kinetics with significant increase in the drug released in pH = 5.5 . Drug released from free methylene blue ( FMB ) gel was significantly higher ( P < 0.05 ) with Higuichi 's diffusion model than LMB gel , which followed zero order kinetics . Free MB gel showed superficial destruction in the mice hair shaft while LMB showed complete destruction of pilosebaceous unit . After only two sessions , there was a 83.3 % reduction in the number of inflammatory acne lesions and a 63.6 % reduction in the number of non-inflammatory acne lesions . At 12 weeks , 90 % of patients had a moderate-to-marked improvement of their acne in the treated areas . Most patients had no pain ; also no serious adverse side effects were recorded . All the patients had no edema . Slight transient hyperpigmentation was seen only in three patients . CONCLUSION Liposomal MB hydrogel selectively delivered MB to sebaceous gl and and was effective in photodynamic treatment of mild-to-moderate acne vulgaris Background : RF‐pulsed light with ELOS technology devices have recently been used to treat acne vulgaris in selected patients . Objective : To investigate the safety and efficacy of a combination of two kinds of device with ELOS technology for the treatment of acne . Methods : Ten patients with moderate acne were treated twice weekly for 4 weeks with the Aurora AC ® ( Syneron Medical Ltd , Yokneam , Israel ) , a combination of pulsed light and RF energy . Immediately after Aurora AC treatment , all patients were treated weekly only on one facial half with the Matrix IR ® ( Syneron Medical Ltd ) , a combination of fractional diode laser and RF energy . Photographic documentations were obtained at baseline , before each treatment session , and 1 and 3 months after the final treatment . Results : At 3 months after treatment , the mean lesion count was reduced by 38 % ( p<0.05 ) after eight treatments with the Aurora AC alone . With additional treatment with the Matrix IR , the mean lesion count was reduced by 61 % . Conclusion : The combination of Aurora AC and Matrix IR was superior in reducing the acne lesion count , and in extending the length of the remission period In this study we have evaluated the use of blue light ( peak at 415 nm ) and a mixed blue and red light ( peaks at 415 and 660 nm ) in the treatment of acne vulgaris . One hundred and seven patients with mild to moderate acne vulgaris were r and omized into four treatment groups : blue light , mixed blue and red light , cool white light and 5 % benzoyl peroxide cream . Subjects in the phototherapy groups used portable light sources and irradiation was carried out daily for 15 min . Comparative assessment between the three light sources was made in an observer‐blinded fashion , but this could not be achieved for the use of benzoyl peroxide . Assessment s were performed every 4 weeks . After 12 weeks of active treatment a mean improvement of 76 % ( 95 % confidence interval 66–87 ) in inflammatory lesions was achieved by the combined blue – red light phototherapy ; this was significantly superior to that achieved by blue light ( at weeks 4 and 8 but not week 12 ) , benzoyl peroxide ( at weeks 8 and 12 ) or white light ( at each assessment ) . The final mean improvement in comedones by using blue – red light was 58 % ( 95 % confidence interval 45–71 ) , again better than that achieved by the other active treatments used , although the differences did not reach significant levels . We have found that phototherapy with mixed blue – red light , probably by combining antibacterial and anti‐inflammatory action , is an effective means of treating acne vulgaris of mild to moderate severity , with no significant short‐term adverse effects BACKGROUND There remains the need for more effective therapeutic options to treat acne vulgaris . Interest in light-based acne treatments has increased , but few r and omized , controlled clinical trials assessing the value of photodynamic therapy ( PDT ) for acne have been reported . AIMS We sought to examine the efficacy of PDT using 5-aminolevulinic acid ( ALA ) and pulsed dye laser therapy in the treatment of acne . PATIENTS / METHODS We conducted a r and omized , controlled , split-face , single-blind clinical trial of 44 patients with facial acne . Patients were r and omized to receive three pulsed dye laser treatments to one side of the face after a 60 - 90 min ALA application time , while the contralateral side remained untreated and served as a control . Serial blinded lesion counts and global acne severity ratings were performed . RESULTS Global acne severity ratings improved bilaterally with the improvement noted to be statistically significantly greater in treated skin than in untreated skin . Erythematous macules ( remnants of previously active inflammatory lesions ) decreased in number in treated skin when compared with control skin and there was a transient but significant decrease in inflammatory papules in treated skin when compared with untreated skin . There were no other statistically significant differences between treated and untreated sides of the face in terms of counts of any subtype of acne lesion . Thirty percent of patients were deemed responders to this treatment with respect to improvement in their inflammatory lesion counts , while only 7 % of patients responded in terms of noninflammatory lesion counts . CONCLUSIONS PDT with the treatment regimen employed here may be beneficial for a subgroup of patients with inflammatory acne Recent advances in light therapy coupled with photosensitizers offer alternatives to topical creams and gels and systemic oral agents for acne treatment . To examine the safety and efficacy of the photosensitizer 5-aminolevulinic acid ( ALA ) in patients with moderate-to-severe acne , a r and omized , split-face study , using ALA on one side of the face , was followed by exposure of the entire face to 532 nm potassium titanyl phosphate ( KTP ) laser . Eight patients completed three treatments for up to 12 weeks . The average acne grading at baseline was 3.20 , and improved to 2.12 at 12 weeks ( 34 % improvement ) . Use of ALA improved acne by 52 % compared with 32 % on the side that did not receive the photosensitizer . Further studies are warranted to establish optimal parameters for photosensitizer use combined with light therapy for treatment of moderate-to-severe acne ; however , the combined use of ALA and a 532 nm laser suggests promising results for acne treatment BACKGROUND AND OBJECTIVES The reaction to intense pulsed light ( IPL ) on Asian skin often differs from that on Caucasian skin . The study reported herein evaluated the effect on acne vulgaris of IPL alone and when IPL was combined with photodynamic therapy ( PDT ) using topical methyl aminolevulinate ( MAL ) in Asians . STUDY DESIGN / MATERIAL S AND METHODS Thirty Chinese subjects with phototypes IV or V and moderate acne were enrolled for a r and omized , half-facial treatment study with IPL alone , IPL with PDT , or as controls . Sixteen percent MAL cream was applied to half of the face 30 minutes before treatment in the PDT group . The IPL was provided by the Ellipse Flex system ( Danish Dermatologic Development , Denmark ) , which emitted wavelengths of 530 to 750 nm . The subjects were treated four times at 3-week intervals . Single passes of double pulses with a 10 milliseconds delay and a pulse duration of 2.5 milliseconds were used . The assessment of inflammatory and non-inflammatory acne lesions by two blinded investigators was based on st and ardized photographs that were taken before each treatment , and at 4 and 12 weeks after the final treatment . RESULTS Twenty-three patients completed the study . The mean reduction of the inflammatory lesion count was 53 % in the PDT group , 22 % in the IPL group , and 72 % in the control group at 4 weeks , and 65 % in the PDT group , 23 % in the IPL group , and 88 % in control group at 12 weeks . The mean clearance of non-inflammatory lesions was 52 % in the PDT group , 15 % in the IPL group , and 14 % in the control group at 4 weeks , and 38 % in the PDT group and 44 % in the IPL group at 12 weeks , when and an increase of 15 % was noted in the control group . Most patients experienced a reduction of inflammatory lesions that was not statistically significant on the PDT-treated side ( P = 0.06 ) or the IPL-treated side ( P = 0.82 ) at 12 weeks after treatment . Pretreatment with MAL result ed in a better clearance of inflammatory acne than IPL alone . There were no statistically significant differences between the intervention groups and the control group in the mean reduction of inflammatory lesions . Significant reductions of non-inflammatory lesions were observed in the MAL-PDT group ( 38 % , P = 0.05 ) and IPL groups ( 43 % , P = 0.00 ) 12 weeks after treatment . Twenty-five percent of the subjects in the PDT group withdrew because of intolerance to procedure-related discomfort . CONCLUSIONS MAL-PDT using IPL and MAL in Asians did not lead to significant improvement of moderate inflammatory acne compared with the control group . However , there was a delayed effect on non-inflammatory lesions , with significant reductions in both the PDT and IPL groups . A proportion of patients could not tolerate the discomfort that was related to PDT despite the short MAL incubation BACKGROUND Photodynamic therapy ( PDT ) with 5-aminolevulinic acid ( ALA ) is an emerging modality for the treatment of acne vulgaris . However , optimal therapeutic protocol s have not been established . OBJECTIVES To compare the efficacies of 3 different light sources for activating ALA-induced protoporphyrin IX for the treatment of acne vulgaris . METHODS Twenty-two patients with moderate to severe acne vulgaris were r and omly assigned to receive ALA-PDT with photoactivation by intense pulsed light ( IPL , 600 - 850 nm ) , a combination of IPL ( 580 - 980 nm ) and bipolar radiofrequency ( RF ) energies , or blue light ( 417 nm ) . Each patient received 3 ALA-PDT sessions at 2-week intervals . Follow-up evaluations were conducted 1 and 3 months after the final treatment . RESULTS At 1 month and 3 months , median lesion count reduction percentages were highest with IPL activation and lowest with blue light activation , although the differences did not reach statistical significance . At 1 month and 3 months , median investigator-assessed improvements were highest with IPL activation and lowest with blue light activation . The variability of responses was significantly smaller with IPL activation than with either RF-IPL or blue light activation . CONCLUSION ALA-PDT with activation by IPL appears to provide greater , longer-lasting , and more consistent improvement than either RF-IPL or blue light activation in the treatment of moderate to severe acne vulgaris Background Blue and red light have been reported to have beneficial effects on acne . However , there has been no double‐blind , r and omized study of acne treatment for combined blue and red light‐emitting diode ( LED ) devices , and the associated molecular mechanisms have rarely been investigated Background To treat moderate to severe acne vulgaris , we developed an optical fiber imported intra-tissue photodynamic therapy : the optical fiber irradiation 5-aminolevulinic acid photodynamic therapy ( OFI-ALA-PDT ) . The aim of this study was to compare the treatment effect and tolerability of OFI-ALA-PDT versus traditional ALA-PDT in the treatment of moderate to severe acne vulgaris . Material / Methods 60 patients with facial acne enrolled into this study were r and omly divided into an OFI-ALA-PDT group and a traditional ALA-PDT group , with 30 patients in each group . The difference between these 2 groups was the red light irradiation methods used . In the OFI-ALA-PDT group we used intra-tissue irradiation ( import the red light directly into the target lesion with optical fiber ) for 5 min , while the traditional ALA-PDT group received whole-face irradiation for 20 min . All patients received 1 irradiation every 7 to 10 days for a total of 6 irradiations . Treatment effects and adverse reactions were recorded after the 4th and 6th irradiation , and at 4 , 8 , 16 weeks after the entire treatment . Results After the 4th irradiation , significantly different effective rates were observed in these groups ( 90.0 % for the OFI-ALA-PDT group and 66.7 % for the control group ) . However , no significant difference in effective rate was recorded in the later observations . There were 182 adverse reactions in the OFI-ALA-PDT group and 497 in the control group , which showed a significant difference ( P<0.05 ) . Conclusions OFI-ALA-PDT showed improved treatment effective rate in the early stage of irradiation , and it had fewer adverse reactions Reporting harms may cause more trouble and discredit than the fame and glory associated with successful reporting of benefits ( 1 ) . The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement , a checklist ( Table 1 ) flow diagram first published in 1996 and revised 5 years later ( 2 , 3 ) , is an effort to st and ardize , and thereby improve , published reports of r and omized , controlled trials ( RCTs ) . One of the additions to the 2001 revision was an item about reporting adverse events . This single item did not do full justice to the importance of harms-related issues . The CONSORT Group met in September 2001 to discuss how to correct this deficiency . We aim ed to provide evidence -based guidance on the reporting of harms in RCTs . First , we search ed MEDLINE , EMBASE , Web of Science , and the Cochrane Library using a wide array of terms related to harms and identified pertinent evidence . We also communicated with experts and review ed bibliographies of identified articles to find additional studies . At a meeting in Montebello , Quebec , Canada , in May 2003 , CONSORT Group members , including several journal editors and additional experts in related fields , held a structured discussion of recommendations about reporting of harms-related issues in RCTs . The discussion s led to a written document that we circulated among the team members for comment . The present manuscript describes our recommendations on the appropriate reporting of harms in RCTs . Table 1 . Original CONSORT Checklist The terminology of harms-related issues in RCTs is confusing and often misleading or misused ( see Glossary ) ( 4 , 5 ) . Safety is a reassuring term that may obscure the real and potentially major harms that drugs and other interventions may cause . We encourage authors to use the term harms instead of safety . In addition to misused terminology , reporting of harms in RCTs has received less attention than reporting of efficacy and effectiveness and is often inadequate ( 6 - 14 ) . In short , both scientific evidence and ethical necessity call for action to improve the quality of reporting of harms in RCTs ( 15 , 16 ) . Here , we present a set of recommendations and accompanying explanations for the proper reporting of harms in RCTs . These recommendations should complement the existing CONSORT statement ( Table 2 ) . Examples are presented on the Annals and CONSORT ( www.consort-statement.org ) Web sites . Table 2 . Checklist of Items To Include When Reporting Harms in R and omized , Controlled Trials Recommendations Title and Abstract Recommendation 1 . If the study collected data on harms and benefits , the title or abstract should so state . The title should mention harms if the study of harms was a key trial objective . Many phase I and phase II trials , some phase II/III trials , and most phase IV trials ( 17 , 18 ) target harms as primary outcomes . Yet , the title and abstract seldom contain the word harm . Among 375143 entries in the Cochrane Central Register of Controlled Trials ( Cochrane Library , issue 3 , 2003 ) , search ing titles with the search terms harm or harms yielded 337 references ( compared with 55374 for efficacy and 23415 for safety ) . Of the 337 , excluding several irrelevant articles on self-harm or harm reduction , only 3 trial reports and 2 abstract s contained the word harm in their titles . Authors should present information on harms in the abstract . If no important harms occurred , authors should so state . Explicit reference to the reporting of adverse events in the title or abstract is also important for appropriate data base indexing and information retrieval ( 19 ) . Introduction Background Recommendation 2 . If the trial addresses both harms and benefits , the introduction should so state . The introduction states the scientific background and rationale of an RCT . This requires a balanced presentation whereby the possible benefits of the intervention under investigation are outlined along with the possible harms associated with the treatment . R and omized , controlled trials that focus primarily on harms should clearly state this interest when describing the study objectives in the Introduction and in defining these objectives in the Methods . Methods Outcomes Recommendation 3 . List addressed adverse events with definitions for each ( with attention , when relevant , to grading , expected vs. unexpected events , reference to st and ardized and vali date d definitions , and description of new definitions ) . The Methods section should succinctly define the recorded adverse events ( clinical and laboratory ) . Authors should clarify whether the reported adverse events encompass all the recorded adverse events or a selected sample . They should explain how , why , and who selected adverse events for reporting . In trials that do not mention harms-related data , the Methods section should briefly explain the reason for the omission ( for example , the design did not include the collection of any information on harms ) . Authors should also be explicit about separately reporting anticipated and unexpected adverse events . Expectation may influence the incidence of reported or ascertained adverse events . Making participants aware in the consent form of the possibility of a specific adverse event ( priming ) may increase the reporting rate of the event ( 20 ) . Another example of priming is the finding that the rates of withdrawals due to adverse events and the rates of specific adverse events were significantly higher in trials of aspirin , diclofenac , or indomethacin with comparator drugs compared with placebo-controlled trials ( 21 ) . Presumably , participants were more eager to come forth and report an adverse event or to withdraw from treatment when they knew they could not be receiving inactive placebo . Authors should report whether they used st and ardized and vali date d measurement instruments for adverse events . Several medical fields have developed st and ardized scales ( 22 - 32 ) . Use of nonvali date d scales is common . The source document for well-established definitions and scales should be referenced . New definitions for adverse events should be explicit and clear . Authors should describe how they developed and vali date d new scales . For interventions that target healthy individuals ( for example , many preventive interventions ) , any harm , however minor , may be important to capture and report because the balance of harms and benefits may easily lean toward harms in a low-risk population . For other population s and for interventions that improve major outcomes ( for example , survival ) , severe and life-threatening adverse events may be the only ones that are important in the balance of benefits and harms . Recommendation 4 . Clarify how harms-related information was collected ( mode of data collection , timing , attribution methods , intensity of ascertainment , and harms-related monitoring and stopping rules , if pertinent ) . It is important to describe the question naires , interviews , and tests used to collect information on harms , as well as their timing during follow-up . Passive surveillance of harms leads to fewer recorded adverse events than active surveillance ( 4 ) . Open-ended questions may yield different information , both quantitatively and qualitatively , than structured question naires ( 33 ) . Studies of nonsteroidal , anti-inflammatory drugs ( NSAIDs ) exemplify how data collection methods can affect the detection and reporting of harms . When selective NSAIDs with fewer gastrointestinal adverse events became available , trials reported more than 10 times as many ulcers when comparing these drugs with older NSAIDs as when older NSAIDs were compared with placebo . In the newer trials , more ulcers were detected because participants had regular endoscopy , and the case definition of ulcers was more sensitive ( 34 ) . Authors should specify the time frame of surveillance for adverse events . Some investigators stop recording adverse events at the end of the intervention period or a certain number of days afterward ( for example , 30 days after discontinuation of drug therapy ) and miss events with long latency ( 35 ) . Surgical trials often capture only the adverse events that occur intraoperatively . Several important surgical complications are likely to occur later . Finally , in crossover trials , delayed events might occur while the patient is taking a subsequent assigned treatment . Attribution is the process of deciding whether an adverse event is related to the intervention . Whenever authors filter events through an attribution process , they should state who makes the attribution ( investigators , participants , sponsors , or combinations ) , whether the process is blinded to assigned treatment , and what definitions of adverse events they use ( 4 ) . Discontinuations and withdrawals due to adverse events are especially important because they reflect the ultimate decision of the participant and /or physician to discontinue treatment . Although treatment may occasionally be discontinued for mild or moderate adverse events , attributing discontinuation to a specific reason ( to toxicity , lack of efficacy , other reasons , or combinations of reasons ) may be difficult . For example , in psychopharmacology , dropouts may reflect treatment ineffectiveness as much as toxicity-related intolerance ( 36 ) . Trial reports should specify who gave the reasons for discontinuation ( participants or physicians ) and whether attribution was blinded to the assigned treatment . For example , even in blinded trials , participants and their clinicians are often unblinded before they decide whether to discontinue the intervention . It is important to report participants who are nonadherent or lost to follow-up because their actions may reflect their inability to tolerate the intervention . Moreover , authors should specify how they h and led withdrawals in the analyses of the data . R and omized , controlled trials should report any plan for monitoring for harms and rules for stopping the trial because of harms ( 37 ) . They should clarify whether stopping guidelines examine benefits and harms In the course of producing the 2009 NHS Evidence - skin disorders Annual Evidence Up date on Acne Vulgaris , 25 r and omised controlled trials were examined . From these , at least 12 potentially serious problems of trial reporting were identified . Several trials concluded no effect of a treatment yet they were insufficiently powered to exclude potentially useful benefits . There were examples of duplicate publication and " salami publication " , as well as two trials being combined and reported as one . In some cases , an incorrect " within-groups " statistical comparison was made and one trial report omitted original efficacy data and included only P values . Both of the non-inferiority studies examined failed to pre-specify a non-inferiority margin . Trials reported as " double-blind " compared treatments that were dissimilar in appearance or had differing adverse effect profiles . In one case an intention-to-treat analysis was not performed and there was a failure to account for all of the r and omized participants . Trial results were made to sound more impressive by selective outcome reporting , emphasizing the statistical significance of treatment effects that were clinical ly insignificant , and by the use of larger-sounding odds ratios rather than rate ratios for common events . Most of the reporting problems could have been avoided by use of the CONSORT guidelines and prospect i ve trial registration on a public clinical trials data base BACKGROUND The 1450-nm diode laser has been known to thermally alter sebaceous gl and s and has been found to be effective for the treatment of inflammatory facial acne . OBJECTIVE Our aim was to evaluate the dose response of a 1450-nm diode laser for treatment of facial acne , sebum production , and acne scarring utilizing two laser fluences and to determine long-term remission after laser treatment . METHODS Twenty patients ( Fitzpatrick skin phototypes II-VI ) received 3 treatments using the 1450 nm diode laser ( 3 - 4 week intervals ) . Split face comparisons were performed by r and omizing patients to one of two fluences ( 14 or 16 J/cm(2 ) ) on the right or left side of the face . Clinical photographs , lesion counts , and sebum measurements were obtained at baseline and after each treatment . Investigators ' and patients ' subjective evaluations of response to treatment were assessed . RESULTS Percentage reductions in mean acne lesion counts from baseline were 42.9 % ( 14 J/cm(2 ) ) and 33.9 % ( 16 J/cm(2 ) ) after one treatment and 75.1 % ( 14 J/cm(2 ) ) and 70.6 % ( 16 J/cm(2 ) ) after 3 treatments . There was persistent reduction of 76.1 % ( 14 J/cm(2 ) ) and 70.5 % ( 16 J/cm(2 ) ) at the 12-month follow-up ( P < .01 ) . Both objective and subjective improvements in acne scarring and sebum production were noted . Treatment-related pain was well tolerated , and adverse effects were limited to transient erythema and edema at treatment sites . LIMITATIONS This was a small study and comparison was limited to two laser fluences . CONCLUSION The 1450-nm diode laser reduced inflammatory facial acne lesions even in Fitzpatrick skin phototypes IV-VI with minimal side effects . Significant improvement in acne lesion counts were noted after the first treatment and was maintained 12 months after the third treatment , indicating significant long-term clinical remission after laser treatment Abstract Introduction : Light and heat devices have become widely used for the treatment of mild-to-moderate inflammatory acne as an alternative to retinoids and antibiotics . The purpose of this study was to examine whether a h and -held device that emits both light and heat energy can safely and effectively be applied at home to shorten the time to improvement and time to resolution of acne papules and pustules . Methods : A two-center , r and omized , placebo-controlled , double-blind study was conducted on 63 subjects with at least four inflamed , facial , acne lesions . Treatments were self-administered twice a day for 4 days . All lesions were photographed on a daily basis . Treatment results were assessed by two blinded evaluators , based on the macro photographs , using a 4-point visual analogue scale ( VAS ) and a photographic lesion reference scale ( PLRS ) , as well as by the subjects . Safety was assessed based on evaluators and subjects ’ reported side effects and adverse events . Results : Twenty-nine subjects in the treatment arm and 32 subjects in the placebo arm , with skin types II – VI , successfully completed the study . Based on blinded VAS scores , 92.24 % of the lesions treated with an active device improved within a median time of 1 day versus 75.78 % and a median time of 2 days for the placebo arm . At 24 hours the improvement rate was 76.72 % for the active arm versus 15.63 % for the placebo arm . Based on blinded PLRS scores , 87.07 % of the lesions treated with an active device improved within a median time of 2 days versus 64.8 % and 3 days for the placebo . A total of 51.7 % of the active arm lesions resolved within a median time of 4 days versus 36 % ( no median ) for the placebo arm lesions . No device-related adverse events occurred throughout the study . Conclusion : This study demonstrates the safety and effectiveness of the h and -held , combined light and heat energy device for at-home treatment of individual mild-to-moderate inflammatory acne lesions . Statistically significant shorter lesion improvement and lesion resolution rates were found Acne vulgaris is an extremely common skin condition . It often leads to negative psychological consequences . Photodynamic therapy ( PDT ) using intense pulsed light has been introduced for effective treatment of acne . The objective was to study the effect of PDT in truncal acne vulgaris using liposomal methylene blue ( LMB ) versus IPL alone . Thirty-five patients with varying degrees of acne were treated with topical 0.1 % LMB hydrogel applied on the r and omly selected one side of the back , and after 60 min the entire back was exposed to IPL . The procedure was done once weekly for three sessions and patients were re-evaluated 1 month after the third session by two independent dermatologists . Acne severity was grade d using the Burton scale . Patient satisfaction using Cardiff Acne Disability Index ( CADI ) was recorded before and after treatment . On LMB-pretreated side , inflammatory acne lesion counts were significantly decreased by 56.40 % compared with 34.06 % on IPL alone . Marked improvement was seen on LMB-pretreated side in 11.5 % of patients compared with 2.8 % on IPL alone . There was a correlation between CADI score and overall improvement . Our study concluded that LMB-IPL is more effective than IPL alone , safe with tolerable pain in the treatment of acne vulgaris on the back . LMB-IPL is more effective than IPL alone , safe with tolerable pain in the treatment of acne vulgaris on the back BACKGROUND Recently , a dem and for safe and effective treatment of acne has been increasing . Although visible light has attracted attention as a new option , the effect of red light alone has not yet been evaluated . OBJECTIVES The objective was to assess the efficacy of red light phototherapy with a portable device in acne vulgaris . METHODS Twenty-eight volunteers with mild to moderate acne were treated with portable red light – emitting devices in this split-face r and omized trial . The right or left side of the face was r and omized to treatment side and phototherapy was performed for 15 minutes twice a day for 8 weeks . Clinical photographs , lesion counts , and a visual analog scale ( VAS ) were used to assess each side of the face at baseline and Weeks 1 , 2 , 4 , and 8 , and a split-face comparison was performed . RESULTS The percent improvement in noninflammatory and inflammatory lesion counts of the treated side was significant compared to the control side ( p<.005 ) . VAS decreased from 3.9 to 1.9 on the treatment side and the difference between the treatment and control sides was significant at Week 8 ( p<.005 ) . CONCLUSIONS This study shows that red light phototherapy alone can be a new therapeutic option for acne vulgaris Abstract Introduction : Blue-light light-emitting diode ( LED ) therapy has become widely used for the treatment of inflammatory acne . In this study we evaluated the efficacy of a home use blue-light LED application in improving lesions and shortening their time to clearance . Methods : This was an IRB approved r and omized self-control study . For each patient ( n = 30 ) , 2 similar lesions , one of each side of the face were chosen for treatment with either a blue-light LED h and -held or sham device . Treatments ( n = 4 ) were conducted twice daily in the clinic and lesions were followed-up till resolution . Reduction in blemishes size and erythema and the overall improvement were evaluated by both the physician and the patients . Time to lesion resolution was recorded . Results : There was a significant difference in the response of lesions to the blue-light LED application as opposed to the placebo in terms of reduction in lesion size and lesion erythema as well as the improvement in the overall skin condition ( p < 0.025 ) . Signs of improvement were observed as early as post 2 treatments . Time to resolution was significantly shorter for the blue-light LED therapy . Conclusion : The results support the effectiveness of using blue-light LED therapy on a daily basis for better improvement and faster resolution of inflammatory acne lesions BACKGROUND Photodynamic therapy ( PDT ) with topical 5‐aminolevulinic acid ( ALA ) is used for effective treatment of facial acne vulgaris . OBJECTIVES To determine which of two different incubation times ( 30 minutes and 3 hours ) is more effective in PDT with intense pulsed light ( IPL ) for acne vulgaris . METHODS & MATERIAL S Twenty Korean subjects with moderate to severe acne were enrolled for a r and omized , half‐facial treatment study . Three sessions with short incubation with ALA plus IPL ( 30 minutes , n=9 ) or long incubation with ALA plus IPL ( 3 hours , n=11 ) on one side of the face and IPL alone on the other side were performed at 1‐month intervals . RESULTS All subjects showed improvement in inflammatory acne lesions after three sessions of ALA‐PDT or IPL alone ( p<.001 in all groups ) . The degree of improvement in inflammatory acne lesions was greater in the long incubation time group than the short incubation time group or the IPL‐alone group , although the mean reduction of inflammatory acne lesions was statistically different only between the long incubation group and the IPL‐only group ( p=.01 ) . There were no statistical differences between the short incubation group and IPL‐alone group . All three groups had decreased sebum secretion after three sessions ( p<.001 in all groups ) , but the differences between groups were not statistically significant . Only transient erythema and mild edema were reported for all treatment groups . CONCLUSION PDT with a long ALA incubation time might be more adequate for a pronounced outcome with inflammatory acne Abstract The treatment of acne vulgaris poses a challenge to the dermatologist , and the disease causes emotional anxiety for the patient . The treatment of acne vulgaris may be well-suited to home-use applications , where sufferers may be too embarrassed to seek medical treatment . This r and omized controlled study is design ed to quantify the effectiveness of using a blue light device in a therapy combined with proprietary creams , in the investigation of a self-treatment regimen . A total of 41 adults with mild-to-moderate facial inflammatory acne were recruited . The subjects were r and omly assigned to combination blue light therapy ( n = 26 ) or control ( n = 15 ) . Photography was used for qualitative assessment of lesion counts , at weeks 1 , 2 , 4 , 8 , and 12 . All subjects in the treatment cohort achieved a reduction in their inflammatory lesion counts after 12 weeks . The mean inflammatory lesion counts reduced by 50.02 % in the treatment cohort , and increased by 2.45 % in the control cohort . The reduction in inflammatory lesions was typically observable at week-3 , and maximal between weeks 8 and 12 . The treatment is free of pain and side-effects . The blue light device offers a valuable alternative to antibiotics and potentially irritating topical treatments . Blue light phototherapy , using a narrow-b and LED light source , appears to be a safe and effective additional therapy for mild to moderate acne OBJECTIVE To evaluate the efficacy and tolerance of a combined 445nm/630 nm light therapy mask for the treatment of mild-to-moderate acne vulgaris with and without topical 1 % salicylic acid with retinol versus 2.5 % benzoyl peroxide . DESIGN A 12-week evaluator-blinded , r and omized study . Subjects were r and omized to be treated with the 445nm/630 nm light therapy mask alone , benzoyl peroxide , or 445nm/630 nm light therapy mask with topical 1 % salicylic acid with retinol . PARTICIPANTS Healthy male and female subjects 12 to 35 years old with Fitzpatrick skin types I to VI and mild-to-moderate facial acne vulgaris . MEASUREMENTS The primary endpoint was the change in the number of inflammatory acne lesions after 12 weeks of treatment . Secondary endpoints included the change in noninflammatory acne lesions , change in total acne lesions , change in Investigator Global Acne Assessment s , and overall responder rate . RESULTS 445nm/630 nm light therapy mask-treated subjects showed a 24.4-percent improvement in inflammatory acne lesions ( p<0.01 ) versus 17.2 percent ( p<0.05 ) and 22.7 percent ( p<0.01 ) in benzoyl peroxide and 445nm/630 nm light therapy mask with topical 1 % salicylic acid with retinol , respectively , a 19.5-percent improvement in noninflammatory lesions ( p<0.001 ) versus 6.3 and 4.8 percent for benzoyl peroxide and 445nm/630 nm light therapy mask with topical 1 % salicylic acid with retinol , respectively . Subjects in the 445nm/630 nm light therapy mask group also achieved a 19.0-percent improvement in the Investigator Global Acne Assessment ( p<0.001 ) versus 4.7 percent in benzoyl peroxide and 13.9 percent in 445nm/630 nm light therapy mask with topical 1 % salicylic acid with retinol ( p<0.01 ) . Treatments were well-tolerated overall with trends toward less early irritation in the 445nm/630 nm light therapy mask group . CONCLUSION 445nm/630 nm light therapy mask appears to be a safe and effective therapy for mild-to-moderate acne CONTEXT The high prevalence of acne vulgaris and its significant morbidity underscore the need for convenient , low-risk , and efficacious therapy . Treatment with various lasers has been reported to improve acne . OBJECTIVE To evaluate the clinical efficacy of pulsed dye laser therapy in the treatment of acne . DESIGN , SETTING , AND PATIENTS R and omized , single-blind , controlled , split-face clinical trial of a volunteer sample of 40 patients aged 13 years or older with facial acne conducted at an academic referral center from August 2002 to September 2003 . INTERVENTION One or 2 nonpurpuric pulsed dye laser treatments to half of the face ( fluence of 3 J/cm2 ) , serial blinded clinical assessment s ( lesion counts ) , and grading of acne severity using st and ardized bilateral serial photographs . MAIN OUTCOME MEASURES Comparison of the changes in lesion counts from baseline to 12 weeks between treated and untreated sides of the face and changes in photographic evidence of acne severity as grade d by a panel of dermatologists blinded to treatment assignment . RESULTS After 12 weeks , using intent-to-treat analysis with last observation carried forward , there were no significant differences between laser-treated and untreated skin for changes in mean papule counts ( -4.2 vs -2.2 ; P = .08 ) , mean pustule counts ( 0 vs -1.0 ; P = .12 ) , or mean comedone counts ( 2.9 vs 1.6 ; P = .63 ) . Grading of serial photographs confirmed the clinical assessment s , showing no significant mean ( SE ) differences in Leeds scores ( range , 1 - 12 ) for treated skin ( 3.98 [ 0.32 ] at baseline and 3.94 [ 0.27 ] at week 12 ) compared with untreated skin ( 3.83 [ 0.32 ] at baseline and 3.79 [ 0.28 ] at week 12 ) ( P>.99 ) . CONCLUSIONS In this study , the nonpurpuric pulsed dye laser therapy did not result in significant improvement of facial acne . More research is needed before this laser therapy may be recommended as an acne treatment Background Acne vulgaris is an acute inflammatory disease of the pilosebaceous units . The bastion of treatment for acne vulgaris has been the use of topical and systemic therapies . Despite many modalities available for treatment , there exists an imperative need for effective noninvasive treatments that reduce the risks of medication side effects . Objective To study the safety and efficacy of the potassium titanyl phosphate ( KTP ) 532 nm pulsed laser for the treatment of acne vulgaris . Methods Twenty-six subjects , clinical ly evaluated with moderate facial acne , were enrolled in this single-center prospect i ve trial . The entire facial area for each subject was divided in half and r and omly design ated as either a treatment or a control side . Each subject was treated with four laser exposures using a KTP 532 nm laser with continuous contact cooling . The results were assessed at 1 and 4 weeks post – final treatment . Primary outcome measures were Michaëlsson acne severity score and adverse treatment effects . Secondary outcome measures included subjective evaluations from the investigator and patients assessing their overall percent satisfaction . Results Primary outcome analysis in the Michaëlsson acne severity score demonstrated a mean 34.9 % ( p = .011 ) and 20.7 % ( p = .25 ) reduction at the 1-week and 4-week post – final treatments , respectively . Subjective investigator evaluations of overall percent satisfaction indicated that all patients demonstrated a minimum 50 % overall satisfaction in treatment outcomes at the 4-week follow-up period . No side effects were encountered . Conclusion Use of the KTP 532 nm laser for the treatment and management of acne vulgaris is both safe and effective , with positive results enduring up to 4 weeks post-treatment BACKGROUND Although effective as a monotherapy for the treatment of inflammatory acne , the 1,450-nm diode laser is associated with considerable pain at higher fluences . MATERIAL S AND METHODS Eleven subjects were treated with a 1,450-nm diode laser in a split-face bilateral paired acne study . One-half of the face received a single-pass consisting of stacked double pulses . The other side received a double-pass treatment of single pulses . Setting s were 11 J/cm2 or lower as tolerated with appropriate dynamic cooling device ( range 25–35 ) . RESULTS The mean pain rating was 5.33 on a 0 to 10 scale on the stacked – pulse treatment side and 5.12 on the double-pass side . Blinded reduction in mean acne lesion counts were 57.6 % and 49.8 % reduction , respectively . An overall acne scar improvement was seen in 83 % of subjects with acne scarring . Transient hyperpigmentation occurred in two patients on the stacked pulse side and completely resolved without sequelae . CONCLUSIONS The pulsed 1,450-nm diode laser can be used at lower fluences that elicit less discomfort yet effectively improve inflammatory acne . Stacking pulses appears to render a slightly higher efficacy than the multipass technique . Single-pulse , multiple-pass treatments may have a lower risk of cryogen-induced transient hyperpigmentation compared to st and ard high fluence techniques BACKGROUND Acne conglobata is hardly curable and easily leads to scar formation after treatment using traditional methods . AIM To develop a novel way to treat acne conglobata . METHODS Seventy-five patients with facial acne conglobata were included in this clinical study and divided into either a treatment group ( n = 35 ) to receive photodynamic therapy ( PDT ) with topical 5 % 5-aminolevulinic acid and red light once every 10 days for a month or a control group ( n = 40 ) to receive a Chinese herbal medicine mask plus red light once per week for the same duration . Patients in both groups were given oral viaminate capsules , doxycycline , zinc gluconate , and topical metronidazole . Efficacy was evaluated with respect to symptom score , cure rate , and response rate up to 2 weeks following the final treatment , and time points for assessment included baseline ( D0 ) , the visit before each treatment ( D10 and D20 for the treatment group , and D7 , D14 , and D21 for the control group ) , and 2 weeks after treatment ( D34 for the treatment group and D35 for the control group ) . Safety was assessed by recording adverse effects . RESULTS Treatment with PDT significantly improved acne lesions and reduced scar formation . The treatment group had a significantly lower symptom score , a higher cure rate , and response rate than the control group . No systemic side effects occurred . CONCLUSION The treatment of acne conglobata with PDT is associated with a high cure rate , short treatment period , few side effects , and reduced scar formation . To the best of our knowledge , this is the first report on the treatment of acne conglobata with PDT BACKGROUND AND OBJECTIVE An alternative approach in the treatment of acne vulgaris is photodynamic therapy ( PDT ) that uses light and aminolevulinic acid (ALA)-induced protoporphyrin IX ( PpIX ) production to eradicate Propionibacterium acnes found in acne lesions . PpIX formation is dependent on ALA percutaneaous penetration . In this study , to enhance ALA penetration and subsequent accumulation of PpIX , skin temperature was increased with radiant infrared ( IR ) prior to ALA-PDT application and compared to ALA-PDT alone in the treatment of inflammatory acne . STUDY DESIGN / MATERIAL S AND METHODS Ten patients exhibiting inflammatory acne with a lesion count of > or = 10 were assigned to a split face or split back group . One side was pre-treated for 15 minutes with radiant IR light emitting diode ( LED ) ( 970 nm ) , while the other side was used as control . ALA was then applied after which PDT LED ( 630 nm ) was performed on the entire face or back surface . Blinded lesion counts and clinical global assessment of severity were performed based on digital photographs before and 4 weeks after the PDT procedure . RESULTS This r and omized , controlled , and rater-blinded trial revealed a significant difference in median reduction of inflammatory lesions on the IR pre-treated ( 73 % , 95 % confidence interval ( CI ) 51 - 81 % ) versus the control side ( 38 % , 95 % CI 8 - 55 % ) 1 month after PDT ( P<0.0001 ) . Clinical assessment of severity was also significantly lower on the IR-treated side than on the control side ( median 1 , 95 % CI 0.74 - 1.34 vs. 2 , 95 % CI 1.17 - 1.72 ) . No unusual treatment-related adverse effects were observed . CONCLUSION The reported therapeutic effects may be due to enhanced induction of alterations in transcutaneous diffusion kinetics of the photosensitizer at higher skin temperature and /or conversion of ALA to PpIX . Pre-PDT radiant IR LED exposure appears to be a promising method to enhance PDT efficacy for the treatment of acne lesions To demonstrate the efficacy of photodynamic therapy using indocyanine green ( ICG ) dye with a diode laser for acne treatment of Asian subjects , an analysis was performed of 16 r and omly chosen Korean patients with acne vulgaris treated by photodynamic therapy for a mean follow up of 2 months . Volunteers were divided into two groups , a single- and multiple-treatment group , in which photodynamic therapy was repeated three times with 1-week intervals . Photodynamic therapy using ICG dye with a diode laser was effective for acne treatment of Korean subjects . However , multiple treatments were not superior to single treatments in controlling acne lesions . Photodynamic therapy combined with ICG dye and diode laser might be an alternative treatment modality for acne in Asian subjects Topical aminolevulinic acid is converted into a potent photosensitizer , protoporphyrin , in human hair follicles and sebaceous gl and s. Photodynamic therapy with topical aminolevulinic acid was tested for the treatment of acne vulgaris , in an open-label prospect i ve human study . Each of 22 subjects with acne on the back was treated in four sites with aminolevulinic acid plus red light , aminolevulinic acid alone , light alone , and untreated control . Half of the subjects were treated once ; half were treated four times . Twenty percent topical aminolevulinic acid was applied with 3 h occlusion , and 150 J per cm2 broad-b and light ( 550 - 700 nm ) was given . Sebum excretion rate and auto-fluorescence from follicular bacteria were measured before , and 2 , 3 , 10 , and 20 wk after , treatment . Histologic changes and protoporphyrin synthesis in pilosebaceous units were observed from skin biopsies . Aminolevulinic acid plus red light caused a transient acne-like folliculitis . Sebum excretion was eliminated for several weeks , and decreased for 20 wk after photodynamic therapy ; multiple treatments caused greater suppression of sebum . Bacterial porphyrin fluorescence was also suppressed by photodynamic therapy . On histology , sebaceous gl and s showed acute damage and were smaller 20 wk after photodynamic therapy . There was clinical and statistically significant clearance of inflammatory acne by aminolevulinic acid plus red light , for at least 20 wk after multiple treatments and 10 wk after a single treatment . Transient hyperpigmentation , superficial exfoliation , and crusting were observed , which cleared without scarring . Topical aminolevulinic acid plus red light is an effective treatment of acne vulgaris , associated with significant side-effects . Aminolevulinic acid plus red light causes phototoxicity to sebaceous follicles , prolonged suppression of sebaceous gl and function , and apparent decrease in follicular bacteria after photodynamic therapy . Potentially , aminolevulinic acid plus red light may be useful for some patients with acne While daylight photodynamic therapy ( PDT ) is a simpler and more tolerable treatment procedure for both clinicians and patients , it has never been applied for acne treatment . In this study , we evaluated efficacy , safety and histological changes of facial acne after application of the novel variant of 5-aminolevulinate (ALA)-ester , 1.5 % 3-butenyl ALA-bu gel , using daylight only as the potential visible light source . Forty-six acne patients were r and omly assigned to either ALA-bu or vehicle application group in a double-blind fashion . Both groups applied the allocated gel to facial acne lesions every other day for 12 weeks . At the final 12 week , both inflammatory and non-inflammatory acne lesions had decreased significantly by 58.0 % and 34.1 % in the ALA-bu group , respectively . Only a few patients expressed mild adverse effects . In the histopathological analysis , attenuated inflammatory cell infiltrations were observed and immunostaining intensities for interleukin-8 , interleukin-1β , matrix metalloproteinase-9 and phosphorylated nuclear factor-κB were reduced concomitantly . Changes of their mRNA expression demonstrated comparable patterns . In conclusion , this ambulatory PDT was effective , very well tolerated and convenient for treating inflammatory acne lesions . Experimental results correlated well with clinical results . This novel regimen would provide a viable option for acne therapy BACKGROUND The effect of combined 585/1,064‐nm ( sequential dual‐wavelength pulsed dye laser ( PDL ) and neodymium‐doped yttrium aluminium garnet ) laser therapy for acne vulgaris has not been evaluated . OBJECTIVES To compare the efficacy and safety of PDL and of combined 585/1,064‐nm laser treatment for mild to moderate facial acne . METHODS A 12‐week , r and omized , prospect i ve , split‐face , double‐blind study was performed . Sixteen participants with mild to moderate acne were treated with a single pass of a combined 585/1,064‐nm laser on half of the face and PDL on the other half during each treatment session . Patients underwent three treatment sessions at 2‐week intervals and were followed up at 8 and 12 weeks after treatment commencement . RESULTS At the final visit , inflammatory acne lesions were reduced by 86 % on the PDL sides and by 89 % on the 585/1,064‐nm laser sides . Noninflammatory acne lesions showed corresponding reductions of 69 % and 64 % , respectively . A significant difference between the two treatments was observed for noninflammatory acne lesions at the eighth week . Histopathologic examinations showed that both treatments decreased inflammation and interleukin‐8 expression and increased transforming growth factor beta expression . CONCLUSIONS PDL and combined 585/1,064 nm laser were safe and effective for the treatment of inflammatory and noninflammatory acne lesions . The authors have indicated no significant interest with commercial supporters BACKGROUND Photodynamic therapy ( PDT ) with methylaminolevulinate ( MAL ) under occlusion is effective for the treatment of acne vulgaris but is associated with significant phototoxic side effects . OBJECTIVE To evaluate the safety and efficacy of topical MAL with or without occlusion followed by red light exposure in patients with facial acne vulgaris . PATIENTS / METHODS Forty-four patients with facial acne vulgaris were r and omized to receive four MAL applications ( 80 mg/g ) at two-week intervals with occlusion on either the right or left side followed 90 minutes later by either 25 or 37 J/cm2 of red light . RESULTS At 18 weeks after the first MAL-PDT treatment , the percentage of inflammatory lesions was reduced by a median of 31.7 , 59.4 , 58.1 and 55.8 percent for patients r and omized to 25 J/cm2 without occlusion , 25 J/cm2 with occlusion , 37 J/cm2 without occlusion and 37 J/cm2 with occlusion respectively . MAL-PDT was , in general , well tolerated and only two patients discontinued their participation due to adverse events . CONCLUSION PDT with MAL at 80 mg/g without occlusion reduces the number of inflammatory lesions in patients with facial acne vulgaris BACKGROUND The 1,450 nm laser has been effective in treating acne . Microdermabrasion may help treat acne and reduce skin barriers to increase the delivery rate of topical anesthetics . OBJECTIVES To evaluate the efficacy , safety , and pain associated with the treatment of inflammatory facial acne with the 1,450 nm laser alone versus microdermabrasion plus the 1,450 nm laser . METHODS Twenty patients with facial acne were treated with the 1,450 nm laser alone and microdermabrasion plus the 1,450 nm laser in a r and omized , split-face trial . RESULTS Laser alone and microdermabrasion plus laser significantly reduced the total number of acne lesions . Mean reductions of 53.5 % and 55.6 % were found after three treatments for laser alone and microdermabrasion plus laser , respectively . Clinical improvement was maintained 12 weeks after the last treatment . Mean pain scores were 5.3±1.5 for microdermabrasion plus laser and 5.2±1.5 for laser alone . There was no statistical difference between treatment levels for efficacy or pain . There was an average 10 % increase in sequential pain as the laser treatment progressed . CONCLUSION The 1,450 nm laser is effective , well tolerated , and safe for treating facial acne . This small pilot study did not demonstrate increased clinical efficacy or decreased associated pain with the addition of microdermabrasion to treatment with the 1,450 nm laser . A larger study may be needed to demonstrate any additional benefit BACKGROUND There is a need for additional effective treatments for acne vulgaris . Laser therapy has been explored as a therapeutic option for acne , but rigorously design ed studies in this area have been limited . OBJECTIVE We sought to examine the efficacy of an infrared laser in the treatment of acne . METHODS We conducted a r and omized , controlled , single-blind , split-face clinical trial of 46 patients with facial acne . Patients received a series of 3 nonablative laser treatments using a novel neodymium : yttrium-aluminum-garnet ( Nd : YAG ) laser to half of the face . Serial blinded lesion counts and global acne severity rating of st and ardized bilateral patient photographs were performed . Sebum production was measured , and patient self- assessment surveys were administered . RESULTS A transient but statistically significant improvement in lesion counts of open comedones was demonstrated in treated skin as compared with untreated skin . There were no significant differences between treated and control sides of the face in terms of changes in mean papule or pustule counts . Grading of serial photographs revealed no significant differences between treated and untreated skin . Patient surveys indicated that the majority of patients found the treatments to be at least mildly effective for both acne and oiliness . LIMITATIONS The current study only addresses the efficacy of a single laser system employing a specific treatment regimen . CONCLUSIONS Infrared laser therapy may improve comedonal acne . Additional work is needed to better define the degree and duration of the effect . Patients appear to positively view such therapy for both acne and oily skin BACKGROUND AND OBJECTIVES Laser treatment using a 1,450 nm diode laser has been shown to improve acne and acne scarring . Its widespread adoption in younger population s has been significantly limited by discomfort . STUDY DESIGN / MATERIAL S AND METHODS Six subjects with active papular acne were treated in a pilot study to determine parameters for a split-face , double-pass , low-energy protocol of 1,450 nm laser treatment . Sides of the face were r and omized to receive single-pass , high-energy treatment ( 13 - 14 J/cm(2 ) ) , or double-pass , low energy treatment ( 8 - 11 J/cm(2 ) ) , for a total of four treatments delivered at monthly intervals . Acne counts and st and ardized , digital photograph were performed 2 months following the final treatment , and compared to pre-treatment counts and photographs . RESULTS Improvement was evaluated comparing pre- and post-treatment photos and averaged 2.5 for the high-energy , single-pass side and 2.3 for the low-energy , double-pass side , using a 0 ( worse ) to 4 ( max improvement ) scale . Acne counts were reduced 78 % on the high-energy , single-pass side and 67 % on the low-energy , double-pass side . Pain ratings on a 1 ( min ) to 10 ( max ) scale averaged 5.6 ( range 1 - 9 ) for the high-energy , single-pass side and 1.3 ( range 1 - 2 ) for the low-energy , double-pass side . CONCLUSIONS Low-energy , double-pass 1,450 nm laser treatment effectively reduces acne counts 2 months post-treatment , and dramatically reduces the pain associated with treatment . The treatment parameters used in this study have eliminated the need for anesthetic cream in daily practice BACKGROUND AND OBJECTIVES The purpose of this study is to evaluate the efficacy of a long pulse diode laser ( Cynosure , Inc. ) to target and destroy enlarged sebaceous gl and s that are preloaded with Indocyanine green ( ICG ) chromophore . STUDY DESIGN / MATERIAL S AND METHODS This study was design ed in three phases . First , preliminary studies were performed to determine the ability of ICG to penetrate into enlarged sebaceous gl and s. Once penetration of the sebaceous gl and was confirmed , the second phase was to determine the necessary parameters for the diode laser to effectively target the ICG loaded gl and s. This was done using laser-tissue interaction analysis . The final phase was done with patients that had active acne on their back to determine if selective destruction of the sebaceous gl and s could be achieved and also to assess the safety and efficacy of this novel treatment for acne . RESULTS Fluorescence microscopy of biopsy sample s show evidence of ICG penetration into the sebaceous gl and s. Histological examination of biopsy sample s from the treated areas finds selective necrosis of the sebaceous gl and s. Preliminary clinical results demonstrate a decrease in acne noted in the treatment area at 3 , 6 , and 10 months follow-up . CONCLUSIONS ICG and diode laser treatment is a new approach for the treatment of acne based on experimentally observed selective photothermolysis of the sebaceous gl and Near infrared ( NIR ) diode laser low-intensity ( soft ) phototherapy with the topical application of indocyanine green ( ICG ) has been suggested for treatment of acne vulgaris . Twelve volunteers with acne lesions on their faces and /or backs were enrolled in the experiment . Skin areas of the subjects that were 4 x 5 cm2 were stained with ICG solution for 5 min before laser irradiation ( 803 nm ) at a power density up to 50 mW/cm2 for 5 to 10 min . For 75 % of the subjects , a single treatment was provided and for the other 25 % , eight sequential treatments over a period of a month were carried out . Observations a month after the completion of the treatment showed that only the multiple treatments with a combination of ICG and NIR irradiation reduced inflammation and improved the state of the skin for a month without any side effects . A month after treatment , the improvement was about 80 % for the group receiving multiple treatments . Single treatments did not have a prolonged effect BACKGROUND AND AIMS Acne vulgaris is common in Asian population s. We compared three methods of phototherapy for the treatment of moderate to severe facial acne vulgaris in Chinese patients . METHODS Patients were r and omly assigned to receive photodynamic therapy ( PDT ) , intense pulsed light ( IPL ) or blue-red light-emitting diode ( LED ) phototherapy to the right side of the face until the inflammatory lesion count reduced by ≥ 90 % . Patients were examined at 1 and 3 months after the final treatment . RESULTS We enrolled 150 patients ( 92 males ; mean age , 28 years ) . At 1 month , ≥90 % clearance or moderate improvement occurred in 46/50 ( 92 % ) , 29/50 ( 58 % ) and 22/50 ( 44 % ) patients in the PDT , IPL and LED groups , respectively ( mean number of sessions required , PDT : 3 ± 1.52 ; IPL : 6 ± 2.15 ; LED : 9 ± 3.34 ) . Forty-six ( 92 % ) patients experienced mild to moderate pain , erythema and edema after PDT , which resolved within 5 - 7 days . Slight erythema and stinging were reported immediately after IPL and LED , resolving within 2 h. After 3 months , minimal papules and pustules were observed in 4 patients in the PDT group , 7 in the IPL group and 12 in the LED group , but no nodular pustules recurred . CONCLUSIONS Phototherapy is efficacious for moderate to severe facial acne vulgaris BACKGROUND Increasing antibiotic resistance of Propionibacterium acnes and growing awareness on the side effects of topical and systemic drugs in the treatment of acne vulgaris by physicians and patients have paved the way for a search into new efficacious and safe treatment modalities such as photodynamic therapy ( PDT ) . Although the efficacy of PDT using 20 % 5-aminolevulinic acid ( ALA ) cream has been established , phototoxic side effects limit its use . The 5-ALA concentration can be lowered by a factor of 40 by changing the vehicle of 5-ALA from a moisturizing cream to liposome encapsulation . OBJECTIVES Assessment of the efficacy and the safety of PDT using 5-ALA 0.5 % in liposomal spray and intense pulsed light ( IPL ) in combination with topical peeling agents ( Li-PDT-PC ) in acne vulgaris . MATERIAL S AND METHODS 32 patients suffering from acne participated in this r and omized , prospect i ve , single blind study . All patients were treated with Li-PDT-PC . During the study nine patients were additionally treated with topical or systemic antibiotics ( Li-PDT-PC-AT ) . These patients were removed from the study although their results were recorded . Results After a mean period of 7.8 months and a mean number of 5.7 treatments the mean total number of lesions dropped from 34.6 lesions to 11.0 lesions , result ing in a mean improvement of 68.2 % . Side effects were minimal . Additionally , an intention to treat analysis was conducted . CONCLUSION Photodynamic therapy of acne vulgaris using 5-ALA 0.5 % liposomal spray and IPL in combination with topical peeling agents is safe and efficacious , even in patients with acne recalcitrant to st and ard therapy The effects of oral zinc sulfate ( corresponding to 135 mg of zinc daily ) alone and in combination with vitamin A ( 300,000 international units ) daily on acne lesions have been compared with those of vitamin A alone and of a placebo . The number of comedones , papules , pustules , and infiltrates were counted at each visit . After four weeks , there was a significant decrease in the number of papules , pustules , and infiltrates in the zinc-treated groups . The effect of zinc plus vitamin A was not better than zinc alone . After 12 weeks of treatment , the mean acne score had decreased from 100 % to 15 % . The mechanism for the effect of zinc therapy in acne , to our knowledge , is not presently known . This article describes a single-center trial involving twenty-two patients with acne vulgaris . Blu-U light was used in all patients , while half were pre-treated with aminolevulinic acid . Preliminary results show promise for this treatment in mild to moderate inflammatory acne vulgaris Acne vulgaris is considered as a therapeutic challenge in terms of managing ongoing symptoms and preventing scar formation . Although there are many available treatments for alleviating acne , therapies for resistant or moderate-to-severe forms have been limited to systemic agents that are accompanied by potentially severe side-effects . While , aminolevulinic acid ( ALA ) photodynamic therapy ( PDT ) has increasingly been used as a simple and safe therapeutic option of acne vulgaris , the clinical efficacy requires confirmation in further studies . The aim of this study was to investigate the efficacy and safety of 5-ALA-PDT in the treatment of moderate-to-severe facial acne vulgaris . A total of 50 patients with moderate-to-severe facial acne were enrolled in the study and r and omly divided equally into a therapy group and a control group . In the therapy group , the patients were treated with 5 % 5-ALA for 1.5 h , followed by three 20-min doses of infrared radiation once a week ; in the control group , the patients were treated with three 20 min doses of infrared radiation without 5-ALA once a week . Both treatments lasted for 3 weeks . The clinical efficacy was determined by evaluating acne lesion counts at weeks 0 , 2 , 4 and 6 . Total efficacy rate ( TER ) was the primary endpoint of the study , and was defined as the proportion of the patients whose treatment effectiveness evaluation was cured ( ≥90 % of skin lesions improved ) and excellent ( 60 - 89 % improvement ) . Adverse effects were recorded throughout the study . The study was completed by 24 patients in the therapy group and 23 patients in the control group . The numbers of acne lesions significantly decreased . The TER of the therapy group was significantly higher than that of the control group at weeks 4 and 6 . Adverse effects were observed in 12 patients of the therapy group and 2 patients of the control group . In the therapy group the most common adverse effect was a burning sensation ( n=7 ) , followed by transient hyperpigmentation ( n=3 ) and acute acneform lesions ( n=2 ) , while in control group , the 2 patients experienced flushing and dryness . The adverse effects were all cured by a symptomatic approach prior to the end of the study . 5-ALA-PDT combined with infrared radiation is an effective and safe therapy for moderate-to-severe facial acne The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating BACKGROUND Low-fluence ( low irradiation energy density ) pulsed-dye lasers ( PDLs ) have been used for atrophic acne scarring , and anecdotal experience suggests that long-term improvements in inflammatory acne can be seen after one PDL treatment . Our aim was to compare the efficacy and tolerability of such PDL treatment with sham treatment in patients with facial inflammatory acne in a double-blind , r and omised controlled trial . METHODS We recruited 41 adults with mild-to-moderate facial inflammatory acne . We r and omly assigned patients to PDL ( n=31 ) or sham treatment ( n=10 ) . Treatment was given at baseline and patients were seen after 2 , 4 , 8 , and 12 weeks . Assessors and participants were unaware of treatment allocations . Primary outcome measures were acne severity after 12 weeks and adverse events at any time . Secondary measures were change in lesion counts after 12 weeks and change in acne severity with time . Analysis was by intention-to-treat . FINDINGS After 12 weeks , acne severity ( measured by Leeds revised grading system ) was reduced from 3.8 ( SD 1.5 ) to 1.9 ( 1.5 ) in the PDL group and 3.6 ( 1.8 ) to 3.5 ( 1.9 ) in the sham group ( p=0.007 ) . Treatment was well tolerated . Total lesion counts fell by 53 % ( IQR 19 to 64 ) in PDL patients and 9 % ( -16 to 38 ) in controls ( p=0.023 ) , and inflammatory lesion counts reduced by 49 % ( 30 to 75 ) in PDL patients and 10 % (-8 to 49 ) in controls ( p=0.024 ) . The most rapid improvements were seen in the first 4 weeks after treatment . INTERPRETATION PDL therapy improves inflammatory facial acne 12 weeks after one treatment with no serious adverse effects Background Photodynamic therapy ( PDT ) involves the activation of a photosensitizing agent by light to produce oxygen intermediates that destroy target tissues . Topical 5-aminolevulinic acid ( ALA ) is converted to protoporphyrin IX , a very potent photosensitizer , which accumulates in human skin , particularly in the epidermis and its appendages . Objective To study the effect of PDT in acne vulgaris using topical ALA and intense pulsed light ( IPL ) . Methods Thirteen individuals with varying degrees of acne were treated after a 3-week washout period . Twenty percent ALA hydrochloride ( DUSA Pharmaceuticals , Wilmington , MA , USA ) was applied to half of the face , and after 3 hours , the whole face was exposed to intense pulsed light ( Quantum SR , Lumenis , Santa Clara , CA , USA ) using a 560 nm cutoff filter starting at a fluence of 26 J/cm . The procedure was done twice at 2-week intervals , and the patients were clinical ly evaluated on the second , fourth , and eighth weeks . Results All patients had no apparent improvement on the second week on both facial halves . In fact , some of the patients developed acute acneiform eruptions on the side treated with ALA . By the fourth week , however , most of the patients had visible improvement of facial acne that was more significant on the ALA-treated side of the face . This persisted until the eighth week post-treatment . On the other h and , the facial half treated with intense pulsed light only showed a return to baseline of their facial acne . Conclusion ALA-IPL are beneficial in the management of acne vulgaris and may be used in combination with other forms of acne treatment or may be an alternative treatment for patients who do not want to take systemic retinoids OBJECTIVES To investigate the efficacy and safety of low-concentration 5-aminolevulinic acid photodynamic therapy ( ALA-PDT ) in the treatment of different severity of acne vulgaris and optimize the treatment regimen . METHODS A self-controlled multicenter clinical trial was carried out in 15 centers throughout China . A total of 397 acne patients of grade II-IV received 3- or 4-session PDT treatment . 5 % ALA gel was applied topically to acne lesions for 1h incubation . The lesions were irradiated by a LED light of 633 nm at dose levels of 96 - 120 J/cm(2 ) . Clinical assessment was conducted before and after every treatment up to 8 weeks . RESULTS The effective rate overall and of grade II , III and IV are 82.1 % , 71.6 % , 79.6 % and 88.2 % , respectively . The effective rate rises significantly proportionally to the severity of acne ( P<0.01 ) . No significant differences are found in the efficacy between patients received 3-session and 4-session PDT treatments ( P>0.05 ) . The count of inflammatory and non-inflammatory acne lesions gradually decrease after each treatment ( P<0.01 ) and during the 8-week follow up ( P<0.01 or P<0.05 ) . Maximum efficacy is obtained at 8 weeks after the treatment completion . CONCLUSIONS A low-dose topical ALA-PDT regimen using 5 % ALA , 1h incubation and red light source of 3 treatment sessions is suggested as optimal scheme for the treatment of different severity of acne vulgaris in Chinese patients . Superior efficacy is found in severe cystic acne of grade IV with mild side effects BACKGROUND Recent studies have shown that photodynamic therapy ( PDT ) is effective in the treatment of acne vulgaris . No studies have compared the treatment effect of aminolevulinic acid-PDT ( ALA-PDT ) and methyl aminolevulinate-PDT ( MAL-PDT ) . OBJECTIVE We sought to compare the treatment effect and tolerability of ALA-PDT versus MAL-PDT in the treatment of acne vulgaris in a controlled r and omized investigator-blinded trial . METHODS Fifteen patients with at least 12 facial inflammatory acne lesions had one split-face PDT treatment with MAL and ALA . RESULTS Twelve weeks after treatment we found a 59 % decrease in inflammatory lesions from baseline , with no significant differences in effectiveness between the two treatments . All patients experienced moderate to severe pain during illumination and developed erythema , pustular eruptions , and epithelial exfoliation after treatment , which were more severe and uniform in the ALA-PDT-treated area . LIMITATIONS The study is paired and controlled , but the results should be evaluated with consideration given for the number of participating patients . CONCLUSION PDT appeared to be an effective treatment for inflammatory acne vulgaris with no significant differences in the response rate between ALA-PDT and MAL-PDT . ALA-PDT result ed in more prolonged and severe adverse effects after treatment BACKGROUND Blue light sources have been shown to be effective in the treatment of mild to moderate inflammatory acne vulgaris lesions . OBJECTIVE We evaluated the safety and efficacy of a new blue light source in the treatment of mild to moderate inflammatory acne vulgaris in comparison to topical 1 % clindamycin solution . RESULTS Blue light therapy reduced inflammatory acne vulgaris lesions by an average of 34 % , as compared to 14 % for topical 1 % clindamycin solution . CONCLUSIONS The blue light source presented in this report is a safe and effective treatment option available to our patients with mild to moderate inflammatory acne lesions BACKGROUND Blue light irradiation is known to be effective against acne . However , the profile of a good c and i date is still unclear . METHODS Thirty-one Taiwanese with symmetrical facial acne were irradiated with blue light on one side of the face selected r and omly twice weekly for 4 consecutive weeks . The other half of the face was left untreated as control . Parameters , including scar type , pore size , and facial follicular porphyrin fluorescence intensity , were documented . The severity of acne was assessed before the treatment , after two , four , and eight sessions of treatment , and 1 month after the treatment was completed . RESULTS Compared with the non-irradiation side , eight sessions of blue light irradiation were effective in acne treatment ( P<0.001 ) . Gender ( P=0.471 ) , scar type ( P-values of pitted , atrophic , and hypertrophic type were 0.688 , 0.572 , and 0.802 , respectively ) , pore size ( P=0.755 ) , and pretreatment fluorescence intensity ( P=0.656 ) could not be used as predictive factors of therapeutic effectiveness . Compared with pretreatment , nodulocystic lesions tended to worsen despite treatment . In addition , the therapeutic effectiveness was not related to the fluorescence intensity change ( P=0.812 ) . CONCLUSIONS Blue light irradiation is effective in acne treatment . Patients without nodulocystic lesions are better c and i date s for blue light irradiation Two 12-week-long double-blind placebo-controlled studies of acne treatments were performed using three judges and a total of 331 male college students . Global severity grade s and papule , pustule , and comedo counts were performed every two weeks . The data were evaluated using Pearson 's coefficient of correlation , and results showed a high degree of correlation between global severity grade s and lesion counts , as well as among judges . These data suggest that acne grading scales and papule counts are equally reproducible methods of grading inflammatory acne and that the comedo grading scale and comedo count are equally reproducible methods of grading comedonal acne BACKGROUND Achieving an effective management of acne vulgaris with minimal complications remains a difficult challenge for physicians . Moreover , the rise in antibiotic-resistant strains reduce the future usefulness of current mainstay therapies , and accordingly , the need for alternative therapies is m and atory . Phototherapy has been shown to be an effective treatment for acne , and there has been a renewed interest in photodynamic therapy as a treatment modality for this condition . OBJECTIVES To evaluate the effectiveness of pulsed dye laser ( PDL ) , intense pulsed light ( IPL ) and light-emitting diode ( LED ) phototherapy for the treatment of moderate to severe acne vulgaris . METHODS Forty-five patients with moderate to severe acne were r and omly divided into 3 equal groups . Group 1 was treated with a PDL , group 2 was treated with IPL , and group 3 was treated with a blue-red combination LED . Treatment was continued until a > or = 90 % clearance of patient lesions was achieved . Clinical assessment s were conducted before starting treatment , at 1 month as a midpoint evaluation , and after the final treatment session . RESULTS Patients treated with the PDL reached a > or = 90 % clearance of their inflammatory lesions after a mean of 4.1 + /- 1.39 sessions , while patients treated with IPL required a mean of 6 + /- 2.05 sessions . Patients treated with the LED required a mean of 10 + /- 3.34 sessions . At the mid-point evaluation , the percent reduction in acne lesions treated with the PDL was 90 % or more , in cases of IPL and the LED , the percent reductions were 41.7 % and 35.3 % , respectively . Laser and light phototherapy sessions were well tolerated with minimal adverse events experienced as being mild and usually self-limiting . CONCLUSIONS The encouraging results of the present study contributes evidence of phototherapy as useful therapeutic option for treatment of moderate to severe acne , and vali date s further studies to evaluate treatments with a larger number of patients and for a longer period of follow-up Background Acne affects 83–95 % of 16‐year‐olds of both sexes , and many seek help from a clinician . Emerging problems with conventional acne treatments , specifically antibiotic resistance of Propionibacterium acnes and fears over the safety and tolerance of oral isotretinoin , create a dem and for novel treatment modalities in acne BACKGROUND Acne is a disease that affects almost all teenagers ( 60 - 90 % ) , and it is the pathology exhibiting the highest morbidity in the 10 - 24 year-olds age group . There are no consistent data at national level by which we can evaluate the preponderance of this pathology in the Portuguese population . OBJECTIVE To estimate the prevalence of acne in teenage school students ( 10 - 12 year-olds ) . STUDY DESIGN A study was carried out involving all 8 regions in the north of Portugal . One school per region was selected at r and om . RESULTS As expected , the figure we obtained for the prevalence of this pathology was high ( 82.4 % ) with males being the most affected . Nevertheless , only 44 % of the affected treated their acne , although the face is the part of the body most affected . In the females high and rogenization ( which is manifested by the presence of hair on the upper lip and on the side of the face ) doubles the median of the degree of acne registered . Regional asymmetry was found in relation to information about the disorder . The degrees of acne are higher in schools in the interior . In the more rural areas , the pharmacist still plays an important role in prescribing treatment . CONCLUSION As a rule , individuals are correctly informed about acne , confirming that the search for treatment and awareness of its value are generally helping to gradually eliminate some of the stigmas from the past The prevalence , severity and disability related to facial acne ( comprising acne on the head and neck ) was assessed in a r and omized sample of 2491 students ( aged 4–18 years ) from schools throughout the State of Victoria in Australia . Students were diagnosed clinical ly by a dermatologist or dermatology registrar . The overall prevalence ( including 4–7 year olds ) was 36.1 % ( 95 % confidence intervals , CI 24.7–47.5 ) , ranging from 27.7 % ( 95 % CI 20.6–34.8 ) in 10–12 year olds to 93.3 % ( 95 % CI 89.6–96.9 ) in 16–18 year olds . It was less prevalent among boys aged 10–12 years than girls of the same age ; however , between the ages of 16 and 18 years , boys were more likely than girls to have acne . Moderate to severe acne was present in 17 % of students ( 24 % boys , 11 % girls ) . Comedones , papules and pustules were the most common manifestations of acne , with one in four students aged 16–18 years having acne scars . Twelve per cent of students reported a high Acne Disability Index score . This tended to correlate with clinical severity , although there was some individual variation in perception of disability . Seventy per cent of those found to have acne on examination had indicated in the question naire that they had acne . Of those , 65 % had sought treatment , a substantial proportion of which ( varying with who gave the advice ) was classified as being likely to have no beneficial effect . This is the first population ‐based prevalence study on clinical ly confirmed acne published from Australia . The results show that acne is a common problem . They suggest the need for education programmes in schools to ensure that adolescents underst and their disease , and know what treatments are available and from whom they should seek advice Abstract Background : Acne vulgaris is a disease of the pilosebaceous unit characterized by the development of inflammatory and /or non-inflammatory lesions that may progress to scars . The increase of bacterial resistance and adverse effects , the teratogenicity of retinoids and lack of response to usual therapies has led to the investigation of new therapeutic alternatives . Objective : To evaluate the role of the pulsed dye laser in the treatment of acne in comparison with other topical therapeutic modalities . Methods : We studied 45 patients with mild to moderate acne . Patients were r and omly divided into three groups : group A received treatment with pulsed dye laser therapy every 2 weeks , group B received topical preparations and group C was subjected to chemical peeling using trichloroacetic acid 25 % . Results : At 12 weeks of treatment , there was a significant improvement of the lesions within each group with the best results seen in group A ; however , no significant difference was detected between the three treatment protocol s after the treatment period . Remission in the follow-up period was significantly higher in the first group . Conclusions : Pulse dye laser therapy mainly improves the inflammatory lesions of acne with few adverse effects Various methods of photodynamic therapy ( PDT ) for acne have been introduced . However , comparative studies among them are still needed . We performed this study to compare the effect of methyl aminolevulinate ( MAL ) PDT for acne between red light and intense pulsed light ( IPL ) . Twenty patients were enrolled in this eight-week , prospect i ve , split-face study . We applied MAL cream over the whole face with a three-hour incubation time . Then patients were irradiated with 22 J/cm(2 ) of red light on one-half of the face and 8 - 10 J/cm(2 ) of IPL on the other half during each treatment session . We performed three treatment sessions at two-week intervals and followed-up patients until four weeks after the last session . Inflammatory and non-inflammatory acne lesions were reduced significantly on both sides . The red light side showed a better response than the IPL side after the first treatment . Serious adverse effects after treatment were not observed . MAL-PDT with red light and IPL are both an effective and safe modality in acne treatment . Red light showed a faster response time than IPL . After multiple sessions , both light sources demonstrated satisfactory results . We suggest that reducing the total dose of red light is desirable when performing MAL-PDT in Asian patients with acne compared with Caucasians BACKGROUND AND OBJECTIVES ALA ( 5-aminolevulinic acid ) photodynamic therapy ( PDT ) is a new treatment option for acne . However , it needs a relatively long incubation period and adverse effects are common . Indole-3-acetic acid ( IAA ) is not toxic by itself but produces free radicals with ultraviolet B. In this study we examined the potential of IAA as a photosensitizer for acne treatment . MATERIAL S AND METHODS Free radical formation was measured after visible light irradiation of IAA . Antimicrobial effect was evaluated by assessing growth suppression of Propionibacterium acnes and Staphylococcus aureus after IAA PDT . To evaluate the histological changes , skin biopsies were performed on nude mice skin after IAA PDT . To evaluate the clinical efficacy of IAA PDT , 14 acne patients were treated with the following IAA PDT regimen : three times each with a 15 minutes incubation period and a 2-week interval . The number of inflammatory lesions and the amount of sebum secretion were then assessed . RESULTS IAA produced free radicals with green light irradiation . Importantly , IAA lost its photosensitizing ability after exposure to certain amount of light . This implies IAA PDT would not require post-procedure photo-protection . The growth of P. acnes and S. aureus were significantly suppressed with IAA PDT . In addition , IAA PDT treated skin showed destruction of follicular ostia epithelium . Interestingly , there was no significant difference between a 4 hours and a 30 minutes incubation , which means that longer absorption time is not necessary for IAA PDT . In the clinical study , inflammatory lesions and sebum secretion were significantly reduced . The procedure was painless and no adverse effect was observed . Photo-protection was not performed and there were no further phototoxic responses . CONCLUSIONS IAA PDT has therapeutic effects on acne via its antimicrobial activities , its sebum-reducing effect and through relieving follicular occlusion . It is a very simple and safe treatment option for acne |
13,589 | 26,921,618 | Overall , iron result ed in fewer anaemic children at follow up , and the end average change in haemoglobin from base line was higher with iron .
Authors ' conclusions Iron treatment does not increase the risk of clinical malaria when regular malaria prevention or management services are provided .
Where re sources are limited , iron can be administered without screening for anaemia or for iron deficiency , as long as malaria prevention or management services are provided efficiently .
12 April 2019 No up date planned Other There is high‐certainty evidence that oral iron supplements do not adversely affect children living in malaria‐endemic areas , meaning further research is unlikely to change our confidence in the estimate of effect . | Abstract Background Iron‐deficiency anaemia is common during childhood .
Iron administration has been cl aim ed to increase the risk of malaria .
Objectives To evaluate the effects and safety of iron supplementation , with or without folic acid , in children living in areas with hyperendemic or holoendemic malaria transmission . | In order to determine whether giving iron to iron-deficient children increases their susceptibility to malaria , 213 Gambian children aged between 6 months and 5 years with iron-deficiency anaemia were r and omized to receive either oral iron or placebo during the rainy season when malaria transmission is maximal . Haematological and iron measurements improved significantly in the group given iron . Regular morbidity surveys showed that fever associated with parasitaemia occurred more frequently in the iron-treated group than in the placebo group . This difference was not significant for all parasitaemias grouped together , but became significant and progressively larger for parasitaemias of ten or more positive fields per 100 high power fields ( P less than 0.025 ) , and for parasitaemias of 50 or more positive fields per 100 high power fields ( P less than 0.01 ) . Three children in the iron-treated group but none in the placebo group had more than one episode of fever and parasitaemia . Splenomegaly rates rose appreciably during the study in both groups , but in children at age 2 years the splenomegaly rate at the end of the study was significantly greater in the iron-treated group . We concluded that there is a significantly increased risk of fever associated with severe malarial parasitaemia for children with iron-deficiency anaemia given iron during the season of maximal malaria transmission in this part of The Gambia OBJECTIVE To determine whether extended oral iron therapy corrects lower developmental test scores in infants with iron-deficiency anemia . STUDY DESIGN Double-blind , controlled trial in Costa Rica involving 32 12- to 23-month-old infants with iron-deficiency anemia and 54 nonanemic control subjects . Anemic infants were treated with orally administered iron for 6 months ; half the nonanemic children were treated with iron and half with placebo . Developmental test scores and hematologic status were evaluated before treatment , after 3 months , and after 6 months . RESULTS Iron-deficient anemic infants received lower mental test scores than nonanemic infants at all three time points ( p < 0.05 pretreatment and at 3 months , p = 0.07 at 6 months ) . There were no significant differences in motor test scores . More of the anemic infants were rated as unusually tearful and unhappy . Anemic infants came from families with lower maternal education and less support for child development and were less likely to be breast fed , were weaned earlier , and consumed more cow milk . CONCLUSIONS Lower mental test scores persisted in infants with iron-deficiency anemia despite extended oral iron therapy and an excellent hematologic response . Iron-deficiency anemia may serve as a marker for a variety of nutritional and family disadvantages that may adversely affect infant development OBJECTIVE To evaluate the effectiveness of universal prophylactic targeting with iron sulfate on daily or weekly basis in the prevention of anemia in infants . METHODS R and omized clinical field trial with children between ages six and 12 months seen at primary health care units in the municipality of Rio de Janeiro , Brazil , between 2004 and 2005 . Three concurrent cohorts were compared : daily group ( n=150 ; 12.5 mg Fe/day ) ; weekly group ( n=147 ; 25 mg Fe/week ) and control group . The intervention consisted of universal supplementation with iron sulfate for 24 weeks , combined with educational adherence-promoting measures . OUTCOME mean serum hemoglobin concentration , distribution and prevalence of anemia ( Hb<110.0 g/l ) at age 12 months . Effectiveness was evaluated considering both intent to treat and adherence to protocol , using multiple regression analysis ( linear and Poisson ) . RESULTS Groups were homogeneous in terms of descriptive variables . The intervention was implemented successfully , with high adhesion to protocol in both groups , and no statistical difference between them . After adjustment , only the daily regimen showed a protective effect . Adherence analysis demonstrated an evident dose-response effect on mean Hb and prevalence of anemia only for the daily regimen . No protective effect was detected for the weekly regimen . CONCLUSIONS Universal supplementation with iron sulfate from six to 12 months of age was effective in increasing serum Hb and decreasing risk of anemia only when administered on a daily basis The effect of iron supplementation on attending behavior of 96 1-y-old infants was assessed in a double-blind , r and omized , controlled trial of iron dextran in Papua New Guinea . The treatment group received an injection of iron dextran at 2 mo ; the controls received a placebo injection . Because many children had malarial parasitemia at testing , presence of malaria was used in the analysis . A significant interaction was found between iron and malaria infection on total fixation time : iron-supplemented groups and placebo-treated parasitemic children showed significantly higher total fixation scores than did placebo-treated aparasitemic children . Blood analysis of iron status showed similar results , with lowest iron status evident in the placebo-treated aparasitemic group . There was no effect of treatment on rate of habituation or dishabituation . Supplemental iron treatment has a significant effect on attention but the direction of the effect depends on the presence of malaria infection OBJECTIVE To assess the effect of an improved local ingredient-based gruel fortified or not with selected multiple micronutrients ( MM ) on Hb concentration of young children . DESIGN In a nutrition centre that we opened in their villages , children received either MM supplement ( containing iron , zinc , vitamin A , vitamin C and iodine ) with the improved gruel ( MMGG ) or the improved gruel only ( GG ) , twice daily , 6 d/week , for 6 months . We assessed baseline and endpoint Hb concentration and anthropometric indices . SETTING Kongoussi , a rural and poor district of Burkina Faso . SUBJECTS In a community-based trial , we r and omly assigned 131 children aged 6 - 23 months with Hb concentrations in the range of 80 - 109 g/l into two groups . RESULTS The groups did not differ significantly at baseline . Mean baseline Hb concentration was 89·2 ( sd 6·5 ) g/l and 90·3 ( sd 8·4 ) g/l in the GG and the MMGG , respectively ( P = 0·42 ) . It increased to 104·1 ( sd 11·4 ) g/l in the GG ( P < 0·001 ) and 107·6 ( sd 14·7 ) g/l in the MMGG ( P < 0·001 ) . The between-group difference of 3·5 ( 95 % CI -1·0 , 8·1 ) g/l in mean ( sd ) endpoint Hb concentration was not significant ( P = 0·13 ) . The endpoint anthropometric indices were not different between the groups . CONCLUSIONS This MM supplement had no additional effect on Hb concentration . Thorough studies are needed to evaluate the actual efficacy of the gruel before its introduction into household routine To assess the effects of iron therapy on developmental test scores in infants with iron deficiency anemia , 68 Guatemalan babies 6 to 24 months of age , with and without mild iron deficiency anemia , were tested with the Bayley Scales of Infant Development before and after one week of oral iron treatment . The two major findings of the study were developmental deficits in the anemic group prior to treatment , and lack of rapid improvement with short-term oral iron therapy . The mean pretreatment Mental Development Index of the anemic group was significantly lower than that of nonanemic infants . The anemic group 's pretreatment Psychomotor Development Index was also lower than that of the nonanemic control group . In a double-blind r and omized study , six to eight days of oral iron therapy did not reverse these deficits . Consequently , the deficits of the anemic group can not be unequivocably attributed to iron lack . However , no significant differences were found between anemic and nonanemic groups in birth histories , socioeconomic level , or general nutritional status which might otherwise explain the lower developmental test scores of the anemic babies Objective : To compare the efficacy of a daily and a weekly iron supplementation on the hematological status of anemic children living at high altitude . Design : Double blind iron supplementation trial including a placebo control group . Setting : A socioeconomically disadvantaged district of La Paz , Bolivia ( altitude of 4000 m ) . Subjects : Anemic ( hemoglobin concentration≤144 g/L ) , 3.3–8.3 y old children of both sexes . Intervention : Children received a placebo ( n=57 ) or a dose of 3–4 mg of elemental iron per kg body weight ( FeSO4 tablets ) 1 d per week ( n=58 ) or 5 d per week ( n=58 ) for 16 weeks . Results : Hemoglobin and zinc erythrocyte protoporphyrin concentrations improved significantly in supplemented groups but not in the placebo group . Changes in hemoglobin during the study were not significantly different between supplemented groups ( weekly group : 15.2±6.9 g/L and daily group : 18.6±11.1 g/L ) but were different from the placebo group ( 0.5±7.1 g/L , P<0.001 ) . At the end of the supplementation period , the hemoglobin distribution was Gaussian , and similar in both supplemented groups . Adjusting for the initial hemoglobin concentration , final hemoglobin and its changes were similar in both supplemented groups . Conclusion : Weekly iron supplementation is as efficacious as daily iron supplementation in improving iron status and correcting moderate iron deficiency anemia in Bolivian school children living at high altitude . Sponsorship : Program supported in part by ORSTROM , the French Ministry of Foreign Affairs and the National Secretary 's Office of Health , Bolivia Iron deficiency and Plasmodium falciparum malaria are the two main causes of anemia in young children in region endemic for this disease . The impact on iron status of prophylactic oral iron supplementation ( 2 mg/kg/day from two to six months of age ) and the duration of this effect were assessed in a group of 832 Tanzanian infants exposed to P. falciparum malaria . Iron parameters and red blood cell indices were assessed at 2 , 5 , 8 , and 12 months of age . Infants who received iron supplements had a significantly lower prevalence of iron deficiency ( P < 0.01 at 5 months and P < 0.001 at 8 and 12 months ) . Red blood cell indices ( mean corpuscular volume , mean cell hemoglobin , and mean cell hemoglobin concentration ) were increased in children receiving iron supplementation and they did not differ between those protected and unprotected against malaria . The prevalence of ferropenia was similar in children protected against malaria and in those who were not protected and did not receive iron supplements ( 34.7 % versus 37.3 % at 12 months of age ) . We concluded that iron supplementation between the ages of 2 - 6 months improves iron status at least up to 12 months of age . Malaria infection does not contribute to iron deficiency We conducted a r and omized controlled trial of the effects of dietary supplements on anemia , weight and height in 136 anemic school children from a low socioeconomic background in Bagamoyo District schools in Tanzania . The aim of the current study was to investigate the impact of dietary supplements on anemia and anthropometric indices of anemic school children . The supplements were vitamin A alone , iron and vitamin A , iron alone or placebo , administered in a double-blinded design for 3 mo . All supplements were provided with local corn meals . Hemoglobin concentration , body weight and height were measured at baseline and at follow-up after supplementation . Vitamin A supplementation increased the mean hemoglobin concentration by 13.5 g/L compared with 3.5 g/L for placebo [ P < 0.0001 , 95 % confidence interval ( CI ) 6.19 - 13.57 ) , the mean body weight by 0.6 kg compared with 0.2 kg for placebo ( P < 0.0001 , 95 % CI 0.19 - 0.65 ) and the mean height by 0.4 cm compared with 0.1 cm for placebo ( P = 0.0009 , 95 % CI 0.08 - 0.42 ) . However , the group of children who received combined vitamin A and iron supplementation had the greatest improvements in all indicators compared with placebo ( 18.5 g/L , P < 0.0001 , 95 % CI 14.81 - 22.23 ; 0.7 kg , P < 0 . 0001 , 95 % CI 0.43 - 0.88 and 0.4 cm , P < 0.0001 , 95 % CI 0.22 - 0.56 for hemoglobin , weight and height , respectively ) . It is likely that vitamin A supplementation may have a useful role in combating the problems of vitamin A deficiency and anemia , as well as in improving children 's growth , in developing countries BACKGROUND Micronutrient deficiencies remain common in preschool children in developing countries . Interventions focus on single micronutrients and often lack effectiveness . Weekly instead of daily supplementation may improve effectiveness . OBJECTIVE The efficacy of weekly and daily supplementation in reducing anemia prevalence and in improving the zinc , vitamin A , and growth status of 6 - 24-mo-old Vietnamese children was investigated . DESIGN In this double-blind , placebo-controlled trial , the daily group ( n = 55 ) received 8 mg elemental Fe ( as iron sulfate ) , 5 mg elemental Zn ( as zinc sulfate ) , 333 microg retinol , and 20 mg vitamin C 5 d/wk for 3 mo . The weekly group ( n = 54 ) received 20 mg Fe , 17 mg Zn , 1700 microg retinol , and 20 mg vitamin C once a week . A third group ( n = 54 ) received a placebo only . Venous blood sample s were collected at the start and end of the supplementation period and anthropometric measurements were taken at the start and 3 mo after the end of supplementation . RESULTS At baseline , 45.6 % of subjects had hemoglobin concentrations < 110 g/L , 36.3 % had zinc concentrations < 10.71 micromol/L , and 45.6 % had retinol concentrations < 0.70 micromol/L. Hemoglobin , retinol , and zinc concentrations of both the weekly and daily groups increased similarly compared with the placebo group ( P < 0.001 ) . There was no significant difference in growth between the supplemented groups and the placebo group . However , the height-for-age of subjects stunted at baseline increased with z scores of 0.48 ( P < 0.001 ) and 0.37 ( P < 0.001 ) for the daily and weekly groups , respectively . CONCLUSIONS Weekly and daily supplementation improved hemoglobin , zinc , and retinol concentrations similarly . Neither intervention affected growth of the overall population , but growth of children stunted at baseline was improved through both types of supplementation BACKGROUND There is still uncertainty about the best procedure to alleviate iron deficiency . Additionally more reliable methods are needed to assess the effect of iron intervention . OBJECTIVE We examined the efficacy of daily iron ( 10 mg ) , daily and weekly multiple-micronutrient supplementation ( 10 and 20 mg Fe , respectively ) in improving body iron stores of Indonesian infants . DESIGN Infants aged 6 - 12 mo were r and omly allocated to 1 of 4 groups : daily multiple-micronutrients ( DMM ) foodlike tablets ( foodLETs ) , weekly multiple-micronutrient ( WMM ) foodLETs , daily iron ( DI ) foodLETs , or daily placebo . Hemoglobin , ferritin , transferrin receptors , and C-reactive protein data were obtained at baseline and 23 wk . RESULTS Body iron estimated from the ratio of transferrin receptors to ferritin was analyzed for 244 infants . At baseline , mean iron stores ( 0.5 + /- 4.1 mg/kg ) did not differ among the groups , and 45.5 % infants had deficits in tissue iron ( body iron < 0 ) . At week 23 , the group DI had the highest increment in mean body iron ( 4.0 mg/kg ) , followed by the DMM group ( 2.3 mg/kg ; P < 0.001 for both ) . The iron stores in the WMM group did not change , whereas the mean body iron declined in the daily placebo group ( -2.2 mg/kg ; P < 0.001 ) . Compared with the daily placebo group , the DMM group gained 4.55 mg Fe/kg , the DI group gained 6.23 mg Fe/kg ( both P < 0.001 ) , and the WMM group gained 2.54 mg Fe/kg ( P = 0.001 ) . CONCLUSIONS When compliance can be ensured , DI and DMM foodLETs are efficacious in improving and WMM is efficacious in maintaining iron stores among Indonesian infants The present study investigates the effect of iron supplementation on measures of school performance among 78 iron-deficient anemic and 41 nonanemic children in an economically deprived rural area in Central Java , Indonesia . All the subjects were treated for ancylostomiasis before iron supplementation . They were r and omly assigned to either an iron or placebo group . Hematological and behavioral measurements were obtained immediately before ( T1 ) and after ( T2 ) the iron and placebo treatments . Iron treatment for a 3-mo period result ed in substantive increases in mean Hgb , Hct , and transferrin saturation among the iron-deficient anemic children . Furthermore , changes in the iron status of iron-deficient anemic children were associated with significant changes in the school achievement test scores of iron-deficient anemic children . T2 evaluation of achievement test scores indicated that the difference between iron-treated anemic and nonanemic children was still statistically significant . However , when T1 scores were entered as a covariate , iron-deficient anemic subjects treated with iron obtained significantly higher delta achievement scores . Findings from the present study indicate that iron supplementation among iron-deficient anemic children benefits learning processes as measured by the school achievement test scores Intermittent iron supplementation has been suggested as a replacement for daily iron supplements for reducing anemia in developing countries . The effects of once weekly and daily iron supplementation on hemoglobin ( Hb ) , serum ferritin ( SF ) , prevalence of anemia , weight and height are compared in this study . Primary schoolchildren ( n = 397 ) from two selected schools in the Hat Yai rural area , southern Thail and , were recruited in 1999 . All children received Albendazole and then r and omly received ferrous sulfate ( 300 mg/tablet ) either daily or weekly , or a placebo for 16 wk . The average increase in Hb was not significantly different between the daily ( mean + /- SD ; 6.5 + /- 6.0 g/L ) and weekly ( 5.7 + /- 6.3 g/L ) groups . However , the average increase in SF was greater ( P < 0.01 ) in the daily ( mean + /- SD ; 39.8 + /- 30.3 microg/L ) than the weekly ( 13.4 + /- 17.3 microg/L ) group . All cases of iron deficiency anemia were abolished in both daily and weekly groups , whereas no reduction in prevalence occurred in the placebo group . Height gain was greater in children who received weekly ( mean + /- SD ; 2.6 + /- 0.9 cm ) than in those who received daily iron ( mean + /- SD ; 2.3 + /- 0.8 cm ) , ( P < 0.01 ) . Weight gain , weight-for-age and height-for-age were not significantly different among the intervention groups . It is concluded that a weekly iron dose is more effective than a daily dose in height gain but not in hematological improvement over 16 wk of supplementation BACKGROUND In developing countries , incomplete resolution of anemia with iron supplementation is often attributed to poor compliance or inadequate duration of supplementation , but it could result from deficiencies of other micronutrients . OBJECTIVE Our objective was to assess children 's hematologic response to supervised , long-term iron supplementation and the relation of this response to other micronutrient deficiencies , anthropometry , morbidity , and usual dietary intake . DESIGN Rural Mexican children aged 18 - 36 mo ( n = 219 ) were supplemented for 12 mo with either 20 mg Fe , 20 mg Zn , both iron and zinc , or placebo . Children were categorized as iron-unsupplemented ( IUS ; n = 109 ) or iron supplemented ( IS ; n = 108 ) . Hemoglobin , hematocrit , mean corpuscular volume , mean cell hemoglobin , plasma concentrations of micronutrients that can affect hematopoiesis , anthropometry , and diet were assessed at 0 , 6 , and 12 mo ; morbidity was assessed biweekly . RESULTS At baseline , 70 % of children had low hemoglobin ( < /=115 g/L ) , 60 % had low hematocrit , 48 % were ferritin deficient , 10 % had deficient and 33 % had low plasma vitamin B-12 concentrations , 29 % had deficient vitamin A concentrations , and 70 % had deficient vitamin E concentrations . Iron supplementation increased ferritin from 11 + /- 14 microg/L at baseline to 31 + /- 18 microg/L after 6 mo ( P < 0.001 ) and 41 + /- 17 microg/L after 12 mo . However , anemia persisted in 30 % and 31 % of supplemented children at 6 and 12 mo , respectively , and was not significantly different between the IUS and IS groups at 12 mo . Initial plasma vitamin B-12 , height-for-age , and dietary quality predicted the hematopoietic response to iron . CONCLUSION Lack of hemoglobin response to iron was associated with indicators of chronic undernutrition and multiple micronutrient deficiencies Iron supplements are often prescribed during infancy but their benefits and risks have not been well documented . We examined whether iron supplements affect growth or morbidity of breast-fed infants . Full-term infants in Sweden ( n = 101 ) and Honduras ( n = 131 ) were r and omly assigned to three groups at 4 mo of age : 1 ) placebo from 4 to 9 mo ; 2 ) placebo from 4 to 6 mo and iron supplements [ 1 mg/(kg . d ) ] from 6 to 9 mo ; or 3 ) iron supplements from 4 to 9 mo . All infants were exclusively or nearly exclusively breast-fed to 6 mo and continued to be breast-fed to at least 9 mo . Growth was measured monthly and morbidity data were collected every 2 wk . Among the Swedish infants , gains in length and head circumference were significantly lower in those who received iron than in those given placebo from 4 to 9 mo . The same effect on length was seen in Honduras , but only at 4 - 6 mo among those with initial hemoglobin ( Hb ) > or = 110 g/L. There was no significant main effect of iron supplementation on morbidity , nor any significant interaction between iron supplementation and site , but for diarrhea ( with both sites combined ) , there was an interaction between iron supplementation and initial Hb . Among infants with Hb < 110 g/L at 4 mo , diarrhea was less common among those given iron than in those given placebo from 4 - 9 mo , whereas the opposite was true among those with Hb > or = 110 g/L ( P < 0.05 ) . We conclude that routine iron supplementation of breast-fed infants may benefit those with low Hb but may present risks for those with normal Hb BACKGROUND Iron deficiency anemia and recurrent infections are common among children of low socioeconomic status . OBJECTIVE The objective was to evaluate the effects of iron supplementation on iron status and morbidity in children with or without infection . DESIGN Children aged 5 - 10 y were recruited for a r and omized , controlled , double-blind study from out patients attending the Children 's Hospital , Colombo , Sri Lanka . Clinical , inflammatory , nutritional , and iron statuses were determined at baseline and after the intervention . Children with a history of recurrent upper respiratory tract infections ( URTIs ) and with laboratory and clinical evidence of a current URTI constituted the infection group ( n = 179 ) , and children without infection constituted the control group ( n = 184 ) . Subjects in both groups were supplemented with ferrous sulfate ( 60 mg Fe ) or placebo once daily for 8 wk . Morbidity from URTIs , the number of gastrointestinal infections , and compliance were recorded every 2 wk . RESULTS The overall prevalence of anemia was 52.6 % . Iron supplementation significantly improved iron status by increasing hemoglobin ( P < 0.001 ) and serum ferritin ( P < 0.001 ) concentrations from baseline values in the children with or without infection . There was no significant improvement in iron status in the children who received placebo . In both the infection group and the control group , the mean number of URTI episodes and the total number of days sick with an URTI during the period of intervention were significantly lower ( P < 0.005 and P < 0.001 , respectively ) in the children who received iron supplements than in those who received placebo . CONCLUSION Iron supplementation significantly improves iron status and reduces morbidity from URTIs in children with or without infection A r and omized , double-blind , placebo-controlled iron supplementation trial was conducted in Kenya to examine the effect of iron supplements on appetite and growth in 87 primary school children . Sustained-release ferrous sulfate ( 150 mg ) or placebo tablets were provided daily at school for 14 wk . Prior to tablet administration , baseline anthropometry , iron nutritional status ( hemoglobin and serum ferritin ) , parasitic infections and clinical indicators of morbidity were measured . A baseline appetite test was conducted twice on each child by quantitatively measuring the ad libitum consumption of a midmorning snack . In addition , each child was asked for a subjective assessment of his or her appetite . Follow-up exams and appetite tests were identical to those at baseline . Findings indicated that provision of iron supplements result ed in improved growth and improved appetite ( in terms of both energy intake of the snack and child report of appetite ) as compared with children receiving the placebo . The increased energy intake from the snack was 10 % of the daily estimated energy intake for children of this same age group living elsewhere in Kenya . Further research into the underlying physiological mechanisms may shed light on the relationship between iron nutritional status and appetite The effect of oral iron supplementation on blood Fe levels and physical growth in 119 rural Indonesian school children was assessed in this double-blind study . The children were classified into anemic and normal groups according to their initial hemoglobin and transferrin saturation levels and were r and omly assigned to either Fe or placebo treatment for 12 wk . Hematological , anthropometric , and morbidity data were collected before and after the treatment period . Before treatment , anemic subjects were smaller and had higher morbidity than normal subjects . Treatment with 10 mg ferrous sulfate.kg-1.d-1 for 12 wk result ed in a significant improvement in anemic subjects ' hematological status , growth velocity , and level or morbidity BACKGROUND Iron deficiency is the most common micronutrient deficiency and affects > 2 billion persons worldwide , leading to anemia in > 40 % of women of reproductive age in the developing world . OBJECTIVE The objective was to determine whether weekly supplementation with iron and folate would reduce the frequency of anemia in teenage women in urban Bangladesh before they became pregnant . DESIGN Participants with a hemoglobin concentration of 80 - 120 g/L were entered into a r and omized , double-blind , placebo-controlled trial and received supplements of placebo , vitamin A , iron + folic acid , or iron + folic acid + vitamin A weekly for 12 wk . The supplements contained 2.42 mg vitamin A ( retinol ) as retinyl palmitate , 120 mg elemental Fe as ferrous sulfate , and 3.5 mg folic acid . RESULTS Hemoglobin concentrations increased significantly more after supplementation with iron + folic acid or iron + folic acid + vitamin A than after either the placebo or vitamin A alone . There was a significantly greater increase in hemoglobin after iron + folic acid + vitamin A than after iron + folic acid , but the additional effect disappeared after adjustment for baseline hemoglobin , serum vitamin A , and ferritin and the number of supplements taken . Those with the lowest baseline hemoglobin had the greatest increase in hemoglobin . Compared with the placebo , iron + folic acid + vitamin A reduced anemia by 92 % , iron deficiency by 90 % , and vitamin A deficiency by 76 % . CONCLUSION There may be significant health benefits from a program that enhances the nutritional status of iron , folate , and vitamin A in poor urban young women before they become pregnant Multiple micronutrient deficiencies are highly prevalent in Indonesia , but the interventions are still focused on single micronutrients . This study aim ed to investigate the efficacy of multiple micronutrient supplements for improving micronutrient status , anemia , growth , and morbidity of Indonesian infants . In this double-blind , placebo-controlled trial , 284 infants aged 6 - 12 mo were r and omly allocated to 4 treatment groups for 23 wk ; 260 ( 92 % ) infants completed the study . Group 1 ( DMM ) received one adequate intake of multiple micronutrient supplements daily ( n = 66 ) ; group 2 ( WMM ) received 2 adequate intakes of multiple micronutrient on 1d plus 6 d of placebo ( n = 60 ) ; group 3 ( DI ) received 10 mg of iron supplement daily ( n = 69 ) ; group 4 received a placebo supplement daily ( n = 65 ) . Blood sample s were collected at baseline and at posttreatment to assess anemia and micronutrient status . Anthropometric measurements were taken monthly , and morbidity was recorded daily . At baseline , 58.1 % of infants were anemic , 34.2 % were iron deficient , 21.3 % were vitamin A deficient , and 11 % were zinc deficient . The DMM and DI supplements both corrected iron deficiency , but DMM supplements were more efficacious in improving hemoglobin levels of anemic infants than the other supplements . However , anemia still persisted in one-third of DMM infants posttreatment . The DMM supplement was more efficacious than WMM or DI supplementation in improving infant status of other micronutrients , including zinc , tocopherol , and riboflavin , whereas DI exacerbated zinc deficiency . There were no significant differences in growth and morbidity among treatment groups , and growth faltering was not prevented BACKGROUND Iron and zinc deficiency are prevalent during infancy in low-income countries . OBJECTIVES The objectives were to examine whether a weekly supplement of iron , zinc , iron+zinc , or a micronutrient mix ( MM ) of 16 vitamins and minerals would alter infant development and behavior . DESIGN The participants were 221 infants from rural Bangladesh at risk of micronutrient deficiencies . Development and behavior were evaluated at 6 and 12 mo of age by using the Bayley Scales of Infant Development II and the Home Observation Measurement of Environment ( HOME ) scale . In this double-blind trial , the infants were r and omly assigned to 1 of 5 treatment conditions : iron ( 20 mg ) , zinc ( 20 mg ) , iron+zinc , MM ( 16 vitamins and minerals , including iron and zinc ) , or riboflavin weekly from 6 to 12 mo . Multivariate analyses were conducted to examine the change in development and behavior for each supplementation group , with control for maternal education , HOME score , months breastfed , anemia , growth at 6 mo , and change in growth from 6 to 12 mo . RESULTS Iron and zinc administered together and with other micronutrients had a beneficial effect on infant motor development . Iron and zinc administered individually and in combination had a beneficial effect on orientation-engagement . Two-thirds of the infants were mildly anemic , no treatment effects on hemoglobin concentration were observed , and hemoglobin was not associated with measures of development or behavior . CONCLUSION The beneficial effects of weekly iron and zinc supplementation on motor development and orientation-engagement suggest that infants benefit from these minerals when administered together BACKGROUND In many developing countries , children are at high risk of both goiter and iron deficiency anemia . Iron deficiency adversely affects thyroid metabolism and may reduce the efficacy of iodine prophylaxis in areas of endemic goiter . OBJECTIVE The aim of this study was to determine whether iron supplementation in goitrous , iron-deficient children would improve their response to iodized salt . DESIGN We conducted a r and omized , double-blind , placebo-controlled trial in 5 - 14-y-old children in Côte d'Ivoire . Goitrous , iron-deficient children ( n = 166 ) consuming iodized salt ( 10 - 30 mg I/kg salt at the household level ) were supplemented with either iron ( 60 mg Fe/d , 4 d/wk for 16 wk ) or placebo . At 0 , 1 , 6 , 12 , and 20 wk , we measured hemoglobin , serum ferritin , serum transferrin receptor , whole-blood zinc protoporphyrin , thyrotropin , thyroxine , urinary iodine , and thyroid gl and volume ( by ultrasonography ) . RESULTS Hemoglobin and iron status at 20 wk were significantly better after iron treatment than after placebo ( P < 0.05 ) . At 20 wk , the mean reduction in thyroid size in the iron-treated group was nearly twice that in the placebo group ( x + /- SD percentage change in thyroid volume from baseline : -22.8 + /- 10.7 % compared with -12.7 + /- 10.1 % ; P < 0.01 ) . At 20 wk , goiter prevalence was 43 % in the iron-treated group compared with 62 % in the placebo group ( P < 0.02 ) . There were no significant differences between groups in whole-blood thyrotropin or serum thyroxine at baseline or during the intervention . CONCLUSIONS Iron supplementation improves the efficacy of iodized salt in goitrous children with iron deficiency . A high prevalence of iron deficiency among children in areas of endemic goiter may reduce the effectiveness of iodine prophylaxis Adolescent girls have high nutrient needs and are susceptible to micronutrient deficiencies . The objective of this study was to test the effect of a multiple-micronutrient-fortified beverage on hemoglobin ( Hb ) concentrations , micronutrient status , and growth among adolescent girls in rural Bangladesh . A total of 1125 girls ( Hb > or = 70 g/L ) enrolled in a r and omized , double-blind , placebo-controlled trial and were allocated to either a fortified or nonfortified beverage of similar taste and appearance . The beverage was provided at schools 6 d/wk for 12 mo . Concentrations of Hb and serum ferritin ( sFt ) , retinol , zinc , and C-reactive protein were measured in venous blood sample s at baseline , 6 mo , and 12 mo . In addition , weight , height , and mid-upper arm circumference ( MUAC ) measurements were taken . The fortified beverage increased the Hb and sFt and retinol concentrations at 6 mo ( P < 0.01 ) . Adolescent girls in the nonfortified beverage group were more likely to suffer from anemia ( Hb < 120 g/L ) , iron deficiency ( sFt < 12 microg/L ) , and low serum retinol concentrations ( serum retinol < 0.70 micromol/L ) ( OR = 2.04 , 5.38 , and 5.47 , respectively ; P < 0.01 ) . The fortified beverage group had greater increases in weight , MUAC , and BMI over 6 mo ( P < 0.01 ) . Consuming the beverage for an additional 6 mo did not further improve the Hb concentration , but the sFt level continued to increase ( P = 0.01 ) . The use of multiple-micronutrient-fortified beverage can contribute to the reduction of anemia and improvement of micronutrient status and growth in adolescent girls in rural Bangladesh Diets of infants across the world are commonly deficient in multiple micronutrients during the period of growth faltering and dietary transition from milk to solid foods . A r and omized placebo controlled trial was carried out in Indonesia , Peru , South Africa , and Vietnam , using a common protocol to investigate whether improving status for multiple micronutrients prevented growth faltering and anemia during infancy . The results of the pooled data analysis of the 4 countries for growth , anemia , and micronutrient status are reported . A total of 1134 infants were r and omized to 4 treatment groups , with 283 receiving a daily placebo ( P ) , 283 receiving a weekly multiple micronutrient supplement ( WMM ) , 280 received a daily multiple micronutrient ( DMM ) supplement , and 288 received daily iron ( DI ) supplements . The DMM group had a significantly greater weight gain , growing at an average rate of 207 g/mo compared with 192 g/mo for the WMM group , and 186 g/mo for the DI and P groups . There were no differences in height gain . DMM was also the most effective treatment for controlling anemia and iron deficiency , besides improving zinc , retinol , tocopherol , and riboflavin status . DI supplementation alone increased zinc deficiency . The prevalence of multiple micronutrient deficiencies at baseline was high , with anemia affecting the majority , and was not fully controlled even after 6 mo of supplementation . These positive results indicate the need for larger effectiveness trials to examine how to deliver supplements at the program scale and to estimate cost benefits . Consideration should also be given to increasing the dosages of micronutrients being delivered in the foodlets Different supplementation schemes to build iron stores in female Indonesian adolescents were investigated . Subjects were 273 high-school girls allocated r and omly to four treatment groups . During a 3-mo period one group received 60 mg Fe , 750 micrograms retinol , 250 micrograms folic acid , and 60 mg vitamin C per day ; a second group received 60 mg Fe , 6000 micrograms retinol , 500 mg folic acid , and 60 mg vitamin C once a week ; a third group received 120 mg Fe and the same amount of the other three micronutrients as the second group once a week ; and a fourth group received only placebos . All subjects were dewormed and supplement allocation was double blind . Blood sample s were collected at baseline , after 2 and 3 mo of supplementation , and 6 mo after the last supplement . After 2 mo of supplementation , groups supplemented weekly and daily showed similar significant improvements ( P < 0.001 ) in hemoglobin and retinol concentrations , and supplementation for 3 instead of 2 mo did not significantly increase these two indicators . After 3 mo , the increase in ferritin was approximately equal to 27 micrograms/L in the daily and 14 - 15 micrograms/L in the weekly groups ( P < 0.001 ) , the latter having a final concentration of 42 - 45 micrograms/L. At 6 mo postsupplementation there were no significant differences among daily and weekly groups , but the ferritin concentration was still approximately equal to 10 - 12-micrograms/L higher ( P < 0.001 ) than in the placebo group . The group supplemented weekly with 60 mg Fe complained less about side effects than the other supplemented groups ( P < 0.05 ) . Weekly supplementation with 60 mg Fe and 6000 micrograms retinol for 3 mo was optimal for improving the iron status of the adolescents for approximately equal to 9 mo The effect of daily vs twice weekly iron supplementation on iron status was studied in preschool children with low iron status in a r and omized double-masked field trial . Subjects ( n = 87 ) were selected on the basis of their hemoglobin concentration being < 111 g/L in finger-prick blood , and were divided into two groups . For 8 wk one group received a daily supplement of 30 mg Fe , while the other group received 30 mg Fe twice per week . A complete data set was obtained from 32 children in the group supplemented daily and from 33 children in the group supplemented twice weekly . Hemoglobin , serum ferritin , and protoporphyrin increased significantly in both groups ( P < 0.001 ) . Changes in hemoglobin and protoporphyrin were correlated with initial hemoglobin concentration ( P < 0.001 ) . The difference in treatment effect between groups was not significant after correction for the initial hemoglobin concentration . It is concluded that in preschool children with low iron status , twice weekly iron supplementation has an effect on iron status similar to that of daily supplementation In developing countries , low food intake is often reported in children < 5 y old . Reduced appetite may be a contributing factor . We investigated whether a combination of a multivitamin-multimineral supplement and additional iron treatment improved appetite and growth of 18- to 30-mo-old stunted and anemic Beninese children . The study was placebo-controlled using VITALIA tablets ( 11 vitamins and 10 minerals ) and ferrous fumarate tablets ( 66 mg of iron ) . One hundred fifty stunted ( height-for-age Z score < -2 ) and anemic children ( hemoglobin < 110 g/L ) were r and omly assigned to one of four groups : group 1 , multivitamin-multimineral plus iron ; group 2 , multivitamin-multimineral plus placebo ; group 3 , placebo plus placebo ; and group 4 , placebo plus iron . Supplementation was daily and supervised for 6 wk . Appetite , knee-heel length , dietary intakes and morbidity were assessed before and after supplementation . Length , weight , arm circumference and hemoglobin concentration were assessed before , just after supplementation and 4 mo after the intervention . Appetite was assessed by means of an appetite test using a test food , riz-au-gras , eaten ad libitum after an overnight fast . Dietary intakes were assessed during three consecutive days in a sub sample by means of the observed weighed record method . Energy intake from the habitual breakfast was significantly correlated with that from the test food ( r = 0.49 , n = 38 , P = 0.002 ) . There were no differences among groups in changes in appetite and growth performance . The habitual diet of the children was monotonous and contained only small amounts of animal products . The morbidity status of the children was comparable in all study groups , before as well as after supplementation . We conclude that the 6-wk multivitamin-multimineral supplementation with additional iron treatment failed to improve the appetite and growth of the children BACKGROUND The pathophysiology of anemia in coastal East Africa is complex . Impaired erythropoietin production is one possible mechanism . Plasmodium falciparum malaria has been found to blunt erythropoietin production , whereas vitamin A stimulates erythropoietin production in vitro . OBJECTIVE We investigated the 72-h effects of vitamin A and the antimalarial drug sulfadoxine pyramethamine ( SP ) on erythropoietin production in severely anemic ( hemoglobin < or = 70 g/L ) preschool children in Zanzibar , a region of known vitamin A deficiency . We hypothesized that both treatments would stimulate erythropoietin production directly , within 72 h , before a change in hemoglobin would occur . DESIGN One hundred forty-one severely anemic children were identified during the baseline assessment of a morbidity sub study of a community-based micronutrient supplementation trial . All severely anemic children were r and omly assigned to receive either vitamin A ( 100,000 or 200,000 IU depending on age ) or SP at baseline ; 72 h later they received the opposite treatment plus daily hematinic syrup for 90 d. Erythropoietic and parasitic indicators were assessed at baseline and again after 72 h. RESULTS After 72 h , SP reduced the malaria parasite density ( by 5029 parasites/microL ; P < 0.001 ) , CRP concentrations ( by 10.6 mg/L ; P = 0.001 ) , and the proportion of children infected with malaria ( by 32.4 % ; P < 0.001 ) . Vitamin A reduced CRP ( by 9.6 mg/L ; P = 0.011 ) , serum ferritin ( by 18.1 microg/L ; P = 0.042 ) , and erythropoietin ( by 194.7 mIU/mL ; P = 0.011 ) concentrations and increased the reticulocyte production index ( by 0.40 ; P = 0.041 ) . CONCLUSIONS Contrary to our hypothesis , vitamin A significantly decreased erythropoietin concentration . The most important effect of both vitamin A and SP was the rapid reduction of inflammation . Vitamin A also mobilized iron from stores and stimulated the production of new erythrocytes Conflicting evidence exists on the possible role of iron supplementation in the predisposition to malaria infection or the enhancement of its clinical severity . Where anemia prevalence is > 40 % , current guidelines are to provide low-dose daily iron to young children for up to 18 mo . Earlier studies used doses higher than the current guidelines , intermittent doses , or have supplemented for duration s < or = 4 mo . We aim ed to assess the effect of low-dose , long-term iron supplementation on malaria infection using a double-blind , placebo-controlled , r and omized design , and to examine possible subgroup effects by season and child age . The study was conducted in Pemba Isl and , Zanzibar , where Plasmodium falciparum malaria has year-round high transmission . A community-based sample of 614 children 4 - 71 mo old was r and omly allocated to 10 mg/d iron or placebo for 12 mo . Outcome measures were the prevalence and density of malaria infection , which was assessed by blood films at monthly intervals . At baseline , 94.4 % were anemic ( hemoglobin < 110 g/L ) , 48.1 % were stunted ( height-for-age Z-score less than -2 ) and > 80 % had malaria-positive blood films . No significant differences in malariometric indices were observed between children in the iron-supplemented and placebo groups . Parasite density was higher in certain months and in younger children , but iron supplementation was not associated with any malarial infection outcome in any season or age subgroup . We conclude that in this environment of high malaria transmission , daily oral low-dose supplementation of iron for 12 mo did not affect the prevalence of malaria infection or parasite density Iron deficiency and helminth infections are two common conditions of children in developing countries . The consequences of helminth infection in young children are not well described , and the efficacy of low dose iron supplementation is not well documented in malaria-endemic setting s. A 12-mo r and omized , placebo controlled , double-blind trial of 10 mg daily iron and /or mebendazole ( 500 mg ) every 3 mo was conducted in a community-based sample of 459 Zanzibari children age 6 - 71 mo with hemoglobin > 70 g/L at baseline . The trial was design ed to examine treatment effects on growth , anemia and appetite in two age subgroups . Iron did not affect growth retardation , hemoglobin concentration or mild or moderate anemia ( hemoglobin < 110 g/L or < 90 g/L , respectively ) , but iron significantly improved serum ferritin and erythrocyte protoporphyrin . Mebendazole significantly reduced wasting malnutrition . but only in children < 30 mo old . The adjusted odds ratios ( AORs ) for mebendazole in this age group were 0.38 ( 95 % CI : 0.16 , 0.90 ) for weight-for-height less than -1 Z-score and 0.29 ( 0.09 , 0.91 ) for small arm circumference . In children < 24 mo old , mebendazole also reduced moderate anemia ( AOR : 0.41 , 0.18 , 0.94 ) . Both iron and mebendazole improved children 's appetite , according to mothers ' report . In this study , iron 's effect on anemia was limited , likely constrained by infection , inflammation and perhaps other nutrient deficiencies . Mebendazole treatment caused unexpected and significant reductions in wasting malnutrition and anemia in very young children with light infections . We hypothesize that incident helminth infections may stimulate inflammatory immune responses in young children , with deleterious effects on protein metabolism and erythropoiesis The choice of iron fortificant usually represents a balance between bioavailability of the compound and its tendency to cause organoleptic problems . The aim of this study was to evaluate the efficacy of sodium iron EDTA ( NaFeEDTA ) and ferrous fumarate at levels compatible with South African brown bread ( 10 mg/kg flour for NaFeEDTA and 20 mg/kg flour for ferrous fumarate ) in a r and omized controlled trial ; electrolytic iron was evaluated at the level currently used in South Africa ( 35 mg/kg flour ) . Schoolchildren ( n = 361 ) , aged 6 - 11 y , from a low socioeconomic community with hemoglobin ( Hb ) < or = 125 g/L were r and omly assigned to 1 of 4 groups that received 4 slices of brown bread supplying either : 1 ) no fortification iron 2 ) 2.35 mg iron as NaFeEDTA ; 3 ) 4.70 mg iron as ferrous fumarate ; and 4 ) 8.30 mg iron as electrolytic iron per intervention day . These amounts simulated a bread intake of 6 slices per day over the 34-wk study period at fortification levels of 0 , 10 , 20 , and 35 mg/kg flour , respectively . Hb concentration and iron status were assessed at baseline and after 34 wk of intervention . The iron interventions did not affect Hb concentration , transferrin saturation , or serum ferritin , iron , or transferrin receptor concentrations relative to the control group . Our results suggest that electrolytic iron at the level currently used in South Africa is not effective in improving iron or Hb status . Neither do NaFeEDTA or ferrous fumarate appear to be suitable alternatives for the fortification of wheat flour when included at levels that do not cause color changes Ninety-nine anemic children aged 1 - 8 y were divided into four groups . Each group was supplemented for 2 mo with vitamin A , iron , vitamin A plus Fe , or a placebo . Clinical , hematological , and Fe biochemical evaluations were performed at the beginning and end of the study . Vitamin A supplementation produced significant elevations in the serum levels of retinol , blood hemoglobin , hematocrit , erythrocytes , serum Fe , and percent transferrin saturation ( % TS ) and had no effect on total Fe binding capacity ( TIBC ) or serum ferritin . Fe supplementation did not affect serum retinol . However , it improved hematological and Fe nutrition indicators , including TIBC and serum ferritin . The simultaneous administration of vitamin A and Fe result ed in a better response of serum Fe and % TS than when the supplement consisted only of vitamin A or Fe alone . Vitamin A benefits hematological condition and Fe metabolism The effect of weekly iron supplementation with and without deworming on hemoglobin was investigated in a double-masked , placebo-controlled field trial . Subjects were 289 preschoolers who were r and omly divided into three groups . Groups 1 and 2 received 30 mg Fe once weekly and group 3 received a placebo . Group 1 additionally received anthelminthic treatment . Supplements were administered by the mothers , who were educated about iron deficiency beforeh and . In the iron-supplemented groups prevalence of anemia decreased from 37.2 % to 16.2 % ( P < 0.001 ) . Hemoglobin increased by an average of 6.9 + /- 9.8 g/L in the two iron-supplemented groups ( n = 191 ) , which was greater ( P < 0.001 ) than the increase of 1.9 + /- 8.0 g/L in the placebo group . None of the subjects had hookworm , and anthelminthic treatment did not have an additional effect . Iron supplements administered once weekly by mothers reduced anemia without major involvement of health staff BACKGROUND The coexistence of multiple micronutrient deficiencies is a widespread public health problem in many regions of the world . Interactions between zinc deficiency and vitamin A metabolism have been reported but no longitudinal studies have evaluated the effect of iron deficiency on vitamin A. OBJECTIVE The objective of this study was to investigate the effect of supplementation with iron , zinc , or both on vitamin A and its metabolically related proteins retinol binding protein ( RBP ) and transthyretin . DESIGN The study was a longitudinal , double-blind , placebo-controlled trial in which 219 rural Mexican children aged 18 - 36 mo were r and omly assigned to receive 20 mg Zn/d , 20 mg Fe/d , 20 mg Zn/d plus 20 mg Fe/d , or placebo . RESULTS Six months after supplementation , plasma retinol increased in all supplemented groups . Compared with placebo , zinc supplementation was associated with significantly higher plasma retinol and transthyretin but the increase in RBP was not significant . Iron supplementation significantly increased plasma retinol , RBP , and transthyretin . Supplementation with zinc plus iron significantly increased plasma retinol but not RBP or transthyretin . Children deficient in zinc , iron , or vitamin A ( as indicated by nutrient plasma concentration ) at the beginning of the study had a significantly greater increase in retinol than did children with adequate nutrient status . CONCLUSIONS Supplementation with zinc , iron , or both improved indicators of vitamin A status . The results of this study agree with previous observations of a metabolic interaction between zinc and vitamin A and suggest an interaction between iron and vitamin A metabolism A r and omized , double-blind , placebo-controlled trial was performed to assess the efficacy of different micronutrient supplementation regimes for improving micronutrient status , preventing anemia , and growth faltering of Vietnamese infants . A population -based sample of 306 infants aged 6 - 12 mo , split in 4 treatment groups , received daily multiple micronutrient ( DMM ) , daily placebo ( P ) , weekly multiple micronutrient ( WMM ) , or daily iron ( DI ) supplements for 6 mo , 7 d/wk , under supervision . Weight and length were measured monthly , and anemia and plasma levels of ferritin , zinc , riboflavin , retinol , tocopherol , and homocysteine were determined before and after the supplementation . Z-scores for length-for-age and weight-for-age worsened significantly in all groups , but the length-for-age Z-score decreased significantly less in the DMM group ( -0.32 + /- 0.05 ) than in the P and WMM groups ( -0.49 + /- 0.05 and -0.51 + /- 0.05 , respectively , P = 0.001 ) . Hemoglobin levels increased significantly more in the DMM group [ mean ( 95%CI ) : 16.4 g/L ( 12.4 - 20.4 ) ] than in the P group [ 8.6 g/L ( 5.0 - 12.2 ) , P = 0.04 ) , with intermediate nonsignificant increases in the WMM [ 15.0 g/L ( 11.5 - 18.5 ) ] and the DI [ 12.9 g/L ( 8.4 - 17.3 ) ] groups . Ferritin changes were significantly greater in DMM ( 12.1 microg/L ) and DI ( 9.5 microg/L ) than in P ( -14.7 microg/L ) and WMM groups ( -9.7 microg/L ) . Of the other micronutrients , only tocopherol showed a significantly greater level in the DMM group compared with P. Anemia still affected a quarter and zinc deficiency affected a third of infants although there was no iron deficiency after 6 mo of supplementation with DMM , suggesting that multiple factors are causing anemia and that the dose of zinc is too small BACKGROUND Iron deficiency and its consequent anemia constitute the commonest micronutrient deficiency in the world . OBJECTIVE We investigated whether long-term , weekly iron-folate supplements administered at school would improve hemoglobin and ferritin concentrations in adolescent girls , including those with mild-to-moderate anemia and hemoglobin concentrations indicating borderline anemia . DESIGN Subjects were 266 girls with hemoglobin concentrations of 80 - 119.9 g/L ( group A ) and 358 girls with hemoglobin concentrations of 120 - 130 g/L ( group B ) who were otherwise healthy . Two hundred sixty-six girls in group A and 268 girls in group B were r and omly assigned to receive either 60 or 120 mg Fe plus 3.5 mg folic acid weekly for 22 wk . Ninety of the girls in group B were r and omly assigned to receive only 5 mg folic acid weekly . Capillary hemoglobin and plasma ferritin were measured at baseline and after 12 and 22 wk of supplementation . RESULTS By the end of the study , 2 % of the girls had dropped out and > 96 % had taken > or = 20 of the 22 tablets ; side effects were minimal . Mean plasma ferritin increased significantly in all iron-supplemented groups , independently of initial hemoglobin values and iron doses . Ferritin concentrations decreased in the girls supplemented with folic acid only . As expected , hemoglobin responses to iron were higher in group A than in group B and increases were positively correlated with initial plasma ferritin . Hemoglobin failed to respond to folate supplementation if initial plasma ferritin concentrations were low . Mean hemoglobin increased significantly and consistently in relation to the length of treatment . CONCLUSION Long-term , weekly iron-folate supplementation was found to be a practical , safe , effective , and inexpensive method for improving iron nutrition in adolescent schoolgirls BACKGROUND Combined supplementation with iron and zinc during infancy may be effective in preventing deficiencies of these micronutrients , but knowledge of their potential interactions when given together is insufficient . OBJECTIVE The goal was to compare the effect in infants of combined supplementation with iron and zinc and of supplementation with single micronutrients on iron and zinc status . DESIGN Indonesian infants ( n = 680 ) were r and omly assigned to daily supplementation with 10 mg Fe ( Fe group ) , 10 mg Zn ( Zn group ) , 10 mg Fe + 10 mg Zn ( Fe+Zn group ) , or placebo from 6 to 12 mo of age . Venous blood sample s were collected at the start and end of the study . Five hundred forty-nine infants completed the supplementation and had both baseline and follow-up blood sample s available for analysis . RESULTS Baseline prevalences of anemia , iron deficiency anemia ( anemia and low serum ferritin ) , and low serum zinc ( < 10.7 micromol/L ) were 41 % , 8 % , and 78 % , respectively . After supplementation , the Fe group had higher hemoglobin ( 119.4 compared with 115.3 g/L ; P < 0.05 ) and serum ferritin ( 46.5 compared with 32.3 microg/L ; P < 0.05 ) values than did the Fe+Zn group , indicating an effect of zinc on iron absorption . The Zn group had higher serum zinc ( 11.58 compared with 9.06 micromol/L ; P < 0.05 ) than did the placebo group . There was a dose effect on serum ferritin in the Fe and Fe+Zn groups , but at different levels . There was a significant dose effect on serum zinc in the Zn group , whereas no dose effect was found in the Fe+Zn group beyond 7 mg Zn/d . CONCLUSION Supplementation with iron and zinc was less efficacious than were single supplements in improving iron and zinc status , with evidence of an interaction between iron and zinc when the combined supplement was given Iron and zinc deficiencies have been associated with delayed motor development in nutritionally at-risk children , albeit inconsistently . In this community-based , r and omized double-blind trial , iron+folic acid ( FeFA ) ( 12.5 mg Fe + 50 mug folic acid ) , zinc ( Zn ) ( 10 mg ) , and iron+folic acid+zinc ( FeFA+Zn ) supplements or a placebo were given daily for 1 y to nutritionally at-risk children in Pemba , Zanzibar . The effects of these treatments on attaining unassisted walking were evaluated using survival analysis for 354 children aged 5 - 11 mo at the start of supplementation . Treatment effects on changes in hemoglobin ( Hb ) and zinc protoporphyrin ( ZPP ) and height-for-age ( HAZ ) and weight-for-age ( WAZ ) Z scores were evaluated using linear regression . Attained motor milestone was recorded every 2 wk for 1 y. Hb , ZPP , HAZ , and WAZ were measured at baseline and after 6 mo of treatment . FeFA with or without Zn reduced the time it took for children to walk assisted . Children who received any iron walked unassisted sooner than those who received no iron [ median difference approximately 15 d , P = 0.035 , risk ratio ( RR ) = 1.28 , 95 % CI = 1.02 , 1.61 ] and this effect was stronger in those who had iron deficiency anemia ( IDA ) at baseline ( median difference was approximately 30 d ; P = 0.002 ; RR = 1.68 ; 95 % CI = 1.21 , 2.32 ) . FeFA alone and Zn alone improved Hb and ZPP compared with placebo . There were no significant treatment effects on changes in HAZ or WAZ . The effects of treatment on time to walking may have been mediated by improvements in iron status or hemoglobin , but were not mediated through improvements in growth Because infants and young children in many developing countries are deficient in both iron and zinc , and zinc can affect iron metabolism , evaluation of optimum strategies to simultaneously supplement iron and zinc is an important public health priority . This study evaluated the efficacy of weekly supplementation of iron or zinc or both on iron , zinc , and copper status in Bangladeshi infants . In a double-blind , r and omized , controlled community trial , 6-mo-old infants were assigned to receive weekly supplements of 1 mg riboflavin ( control , n = 82 ) or 1 mg riboflavin + 20 mg iron ( n = 83 ) , 20 mg zinc ( n = 83 ) , or both ( n = 85 ) for 6 mo . Hemoglobin , serum ferritin , transferrin receptor , zinc , and copper concentrations were measured at baseline and at the end of intervention . Serum Zn increased in both groups receiving zinc ; the increase was greatest among children with low baseline serum zinc concentration . Iron status indicators did not differ among the groups before or after 6 mo of supplementation . Supplementation with either zinc or iron decreased serum copper after 6 mo . Joint supplementation did not alter the individual effects of iron or zinc supplementation in these Bangladeshi children . However , the dosing regimen may not have been adequate to achieve the desired biochemical effects BACKGROUND Iron supplementation has been associated with greater susceptibility to malaria and lower hematologic responses in pregnant Gambian women with sickle cell trait ( HbAS ) than in similar women with the normal ( HbAA ) phenotype . It is not known whether a similar interaction exists in children . OBJECTIVE Our aim was to determine the influence of the HbAS phenotype on hematologic responses and malaria after iron supplementation in anemic ( hemoglobin : 70 - 109 g/L ) children aged 2 - 35 mo . DESIGN We conducted a double-blind , r and omized , placebo-controlled trial ( HbAS , n = 115 ; HbAA , n = 408 ) of intermittent preventive treatment with sulfadoxine pyrimethamine ( IPT-SP ) at 4 and 8 wk and daily supervised iron for 12 wk . RESULTS The mean difference in hemoglobin concentrations at 12 wk between children assigned iron and placebo iron , after adjustment for the effect of IPT-SP , was 9.1 g/L ( 95 % CI : 6.4 , 11.8 ) and 8.2 g/L ( 4.0 , 12.4 ) in HbAA and HbAS children , respectively ( P for interaction = 0.68 ) . Although malaria parasitemia and clinical malaria occurred more often in HbAS children in the iron group than in those in the placebo iron group , this difference was not significant ; incidence rate ratios were 1.23 ( 95 % CI : 0.64 , 2.34 ) and 1.41 ( 0.39 , 5.00 ) , respectively . The corresponding incidence rate ratios in HbAA children in the same groups were 1.07 ( 95 % CI : 0.77 , 1.48 ) and 0.59 ( 0.35 , 1.01 ) , respectively . The corresponding interactions between the effects of iron and hemoglobin phenotype were not significant . CONCLUSIONS There was no evidence for a clinical ly relevant modification by the hemoglobin S phenotype of the effects of iron supplementation in the treatment of mild anemia . The benefits of iron supplementation are likely to outweigh possible risks associated with malaria in children with the HbAA or HbAS phenotype In this study the effects of supplementation of iron and zinc , alone or combined , on iron status , zinc status and growth in Indonesian infants is investigated . Micronutrient deficiencies are prevalent in infants in developing countries , and deficiencies often coexist ; thus , combined supplementation is an attractive strategy . However , little is known about interactions between micronutrients . In a r and omized , double-blind , placebo-controlled supplementation trial , 478 infants , 4 mo of age , were supplemented for 6 mo with iron ( 10 mg/d ) , zinc ( 10 mg/d ) , iron + zinc ( 10 mg of each/d ) or placebo . Anthropometry was assessed monthly , and micronutrient status was assessed at the end of supplementation . Supplementation significantly reduced the prevalence of anemia , iron deficiency anemia and zinc deficiency . Iron supplementation did not negatively affect plasma zinc concentrations , and zinc supplementation did not increase the prevalence of anemia or iron deficiency anemia . However , iron supplementation combined with zinc was less effective than iron supplementation alone in reducing the prevalence of anemia ( 20 % vs. 38 % reduction ) and in increasing hemoglobin and plasma ferritin concentrations . There were no differences among the groups in growth . The growth of all groups was insufficient to maintain the same Z-scores for height for age and weight for height . There is a high prevalence of deficiencies of iron and zinc in these infants , which can be overcome safely and effectively by supplementation of iron and zinc combined . However , overcoming these deficiencies is not sufficient to improve growth performance in these infants To evaluate the effect of long-term oral iron supplementation on growth , 250 children aged 6 - 71 mo were studied in a r and omized double-blind controlled trial . The intervention group received 125 mg of ferrous gluconate ( 15 mg elemental iron ) plus multivitamins ( vitamins A , D and C ) ; the comparison group received only multivitamins daily for 12 mo . Weight ( kg ) and height ( cm ) were measured every month . Eighty three percent of the children continued the treatment for one year . The weight increment over the 12-mo period was 1.35 + /- 0.65 kg ( mean + /- SD ) in the intervention group and 1.39 + /- 0.54 kg in the comparison group . The height increments were 6.01 + /- 1.47 and 6.18 + /- 1.58 cm in the intervention and comparison groups , respectively . Mean weight and height increments did not differ ; in an analysis stratified according to different age and nutritional categories , they also did not differ between the two groups , indicating that long-term iron supplementation does not increase growth in children Linear growth retardation and anemia are the most prevalent nutritional problems in the world ; effective interventions are urgently needed . We evaluated Ecuador 's National Food Nutrition Program ( PANN 2000 ) that included a micronutrient-fortified complementary food ( FCF ) , Mi Papilla , in poor periurban and rural communities of Ecuador . The program is preventive and targeted to all infants and young children living in poor communities and receiving government health services . We compared dietary intake , micronutrient status , and growth over 11 mo in a cohort of children from the catchment areas of the PANN 2000 with same-age control children in nearby communities eligible to enter the program 1 y later . PANN 2000 children enrolled in the program when they were age 9 - 14 mo and were age 20 - 25 mo at the final survey . They consumed significantly more energy , protein , fat , iron , zinc , vitamin A , and calcium than control children because of their FCF consumption . Anemia , 76 % in both groups at baseline , fell to 27 % in PANN 2000 children but only to 44 % in control children ( P < 0.001 ) . The odds of being anemic were 58 % lower for PANN 2000 children ( P = 0.003 ) . The effects on linear growth and weight were limited to children who were older when the program began ( 12 - 14 mo ) and were significant for weight ( interaction with age , 0.38 kg ; P = 0.029 ) and positive but not significant for length ( 0.66 cm ; P = 0.08 ) . An FCF , including ferrous sulfate , delivered through public health services , is highly effective in improving weight and hemoglobin and reducing anemia A recent meta- analysis of 14 clinical trials indicated that daily compared with intermittent iron supplementation result ed in significantly greater hematological improvement in pregnant women . No such definitive beneficial effect was demonstrated in preschool children . We compared the efficacy of daily and twice weekly iron supplementation for 6 wk under supervised and unsupervised conditions in the treatment of mild and moderate anemia [ hemoglobin ( Hb ) 50 - 109 g/L ] in children aged 2 - 59 mo living in a malaria-endemic area of western Kenya . The study was a cluster-r and omized trial using a factorial design ; participants were aware of the treatment assigned . All children ( n = 1049 ) were administered a single dose of sulfadoxine-pyrimethamine at enrollment followed by 6 wk of daily supervised iron supplementation [ 3 - 6 mg/(kg.d ) ] , twice weekly supervised iron supplementation [ 6 - 12 mg/(kg.wk ) ] , daily unsupervised iron supplementation , or twice weekly unsupervised iron supplementation . In the supervised groups , Hb concentrations at 6 and 12 wk ( 6 wk postsupplementation ) were significantly higher in children given iron daily rather than twice weekly [ mean ( 95 % CI ) difference at 6-wk : 4.2 g/L ( 2.1 , 6.4 ) ; 12-wk : 4.4 g/L ( 1.8 , 7.0 ) ] . Among the unsupervised groups , Hb concentrations were not different at 6 wk [ mean ( 95 % CI ) difference : 0.86 g/L ( -1.4 , 3.1 ) ] , but significantly higher at 12 wk for those assigned daily iron [ mean ( 95 % CI ) difference : 3.4 g/L ( 0.79 , 6.0 ) , P = 0.02 ] . In this malarious area and after initial antimalarial treatment , 6 wk of daily iron supplementation results in better hematological responses than twice weekly iron supplementation in the treatment of anemia in preschool children , regardless of whether adherence can be ensured Iron deficiency is prevalent in children and infants worldwide . Zinc deficiency may be prevalent , but data are lacking . Both iron and zinc deficiency negatively affect growth and psychomotor development . Combined iron and zinc supplementation might be beneficial , but the potential interactions need to be verified . In a r and omized , placebo-controlled trial using 2 x 2 factorial design , 609 Thai infants aged 4 - 6 mo were supplemented daily with 10 mg of iron and /or 10 mg of zinc for 6 mo to investigate effects and interactions on micronutrient status and growth . Iron supplementation alone increased hemoglobin and ferritin concentrations more than iron and zinc combined . Anemia prevalence was significantly lower in infants receiving only iron than in infants receiving iron and zinc combined . Baseline iron deficiency was very low , and iron deficiency anemia was almost nil . After supplementation , prevalence of iron deficiency and iron deficiency anemia were significantly higher in infants receiving placebo and zinc than in those receiving iron or iron and zinc . Serum zinc was higher in infants receiving zinc ( 16.7 + /- 5.2 micromol/L ) , iron and zinc ( 12.1 + /- 3.8 micromol/L ) or iron alone ( 11.5 + /- 2.5 micromol/L ) than in the placebo group ( 9.8 + /- 1.9 micromol/L ) . Iron and zinc interacted to affect iron and zinc status , but not hemoglobin . Iron supplementation had a small but significant effect on ponderal growth , whereas zinc supplementation did not . To conclude , in Thai infants , iron supplementation improved hemoglobin , iron status , and ponderal growth , whereas zinc supplementation improved zinc status . Overall , for infants , combined iron and zinc supplementation is preferable to iron or zinc supplementation alone BACKGROUND Micronutrient deficiencies are common during infancy , and optimal approaches for their prevention need to be identified . OBJECTIVE The objective was to compare the efficacy and acceptability of Sprinkles ( SP ) , crushable Nutritabs ( NT ) , and fat-based Nutributter ( NB ; 108 kcal/d ) , which provide 6 , 16 , and 19 vitamins and minerals , respectively , when used for home fortification of complementary foods . DESIGN Ghanaian infants were r and omly assigned to receive SP ( n = 105 ) , NT ( n = 105 ) , or NB ( n = 103 ) daily from 6 to 12 mo of age . We assessed dietary intake , morbidity , and compliance weekly . Hemoglobin and plasma ferritin , TfR , C-reactive protein , and zinc were measured at 6 and 12 mo . We used an exit interview to assess acceptability . A r and omly selected control group of infants who received no intervention ( NI ; n = 96 ) were assessed at 12 mo . RESULTS All supplements were well accepted , and the mean percentage of days that supplements were consumed ( 87 % ) did not differ between groups . At 12 mo , all 3 intervention groups had significantly higher ferritin and lower TfR concentrations than did the NI control group . Mean ( + /- SD ) hemoglobin was significantly higher in NT ( 112 + /- 14 g/L ) and NB ( 114 + /- 14 g/L ) but not in SP ( 110 + /- 14 g/L ) infants than in NI infants ( 106 + /- 14 g/L ) . The prevalence of iron deficiency anemia was 31 % in the NI control group compared with 10 % in the intervention groups combined ( P < 0.0001 ) . CONCLUSION All 3 options for home fortification of complementary foods are effective for reducing the prevalence of iron deficiency in such population Hemoglobin and ferritin are important biomarkers of iron status but are both altered by inflammation . We used the inflammation biomarkers C-reactive protein ( CRP ) and alpha1-acid glycoprotein ( AGP ) to adjust hemoglobin and ferritin concentrations to clarify interpretation of iron status . Apparently healthy adults who tested positive twice for HIV but who had not reached stage IV or clinical AIDS were r and omly allocated to receive a food supplement ( n = 17 and 21 ) or the food plus a micronutrient capsule ( MN ; 10 men and 34 women , respectively ) containing 30 mg iron/d . Hemoglobin , ferritin , CRP , and AGP concentrations were measured at baseline and 3 mo and subjects were divided into 4 groups ( reference , no inflammation ; incubating , raised CRP ; early convalescence , raised AGP and CRP ; and late convalescence , raised AGP ) . Correction factors ( the ratios of the median for the reference group over each inflammatory group ) improved the consistency of the ferritin but not the hemoglobin results . After correction , ferritin ( but not hemoglobin ) increased in both men ( 48 microg/L ; P = 0.02 ) and women ( 12 microg/L ; P = 0.04 ) who received MN but not in the food-only group . However , hemoglobin did improve in subjects who showed no inflammation both at baseline and mo 3 ( P = 0.019 ) , but ferritin did not increase in this group . In conclusion , ferritin concentrations were more closely linked to current inflammation than hemoglobin ; hence , correction by inflammation biomarkers improved data consistency . However , low hemoglobin concentrations were the consequence of long-term chronic inflammation and improvements in response to MN supplements were only detected in subjects with no inflammation BACKGROUND Deficiencies of iron and zinc are associated with delayed development , growth faltering , and increased infectious-disease morbidity during infancy and childhood . Combined iron and zinc supplementation may therefore be a logical preventive strategy . OBJECTIVE The objective of the study was to compare the effects of combined iron and zinc supplementation in infancy with the effects of iron and zinc as single micronutrients on growth , psychomotor development , and incidence of infectious disease . DESIGN Indonesian infants ( n = 680 ) were r and omly assigned to daily supplementation with 10 mg Fe ( Fe group ) , 10 mg Zn ( Zn group ) , 10 mg Fe and 10 mg Zn ( Fe+Zn group ) , or placebo from 6 to 12 mo of age . Anthropometric indexes , developmental indexes ( Bayley Scales of Infant Development ; BSID ) , and morbidity were recorded . RESULTS At 12 mo , two-factor analysis of variance showed a significant interaction between iron and zinc for weight-for-age z score , knee-heel length , and BSID psychomotor development . Weight-for-age z score was higher in the Zn group than in the placebo and Fe+Zn groups , knee-heel length was higher in the Zn and Fe groups than in the placebo group , and the BSID psychomotor development index was higher in the Fe group than in the placebo group . No significant effect on morbidity was found . CONCLUSIONS Single supplementation with zinc significantly improved growth , and single supplementation with iron significantly improved growth and psychomotor development , but combined supplementation with iron and zinc had no significant effect on growth or development . Combined , simultaneous supplementation with iron and zinc to infants can not be routinely recommended at the iron-to-zinc ratio used in this study Given the high prevalence of micronutrient deficiencies and infectious diseases in infants in developing countries , an evaluation of the efficacy of different micronutrient formulations on infant morbidity is a priority . The efficacy of weekly supplementation of four different micronutrient formulations on diarrhea and acute lower respiratory infection ( ALRI ) morbidity was evaluated in Bangladeshi infants . In a double-blind , r and omized , controlled community trial , 799 infants aged 6 mo were r and omly assigned to one of the following 5 groups : 1 ) 20 mg elemental iron with 1 mg riboflavin , 2 ) 20 mg elemental zinc with 1 mg riboflavin , 3 ) 20 mg iron and 20 mg zinc with 1 mg riboflavin , 4 ) a micronutrient mix ( MM ) containing 20 mg iron , 20 mg zinc , 1 mg riboflavin along with other minerals and vitamins and 5 ) a control treatment , 1 mg riboflavin only . Health workers visited each infant weekly until age 12 mo to feed the supplement and to collect data on diarrhea and ALRI morbidity . Hemoglobin , serum ferritin and serum zinc levels of a sample of infants were measured at 6 and 12 mo . Compared with the control group , at 12 mo , serum ferritin levels were higher in the iron + zinc group , and serum zinc levels were higher in the zinc and iron + zinc groups . Simultaneous supplementation with iron + zinc was associated with lower risk of severe diarrhea , 19 % lower in all infants and 30 % lower in less well-nourished infants with weight-for-age Z-score below -1 . Iron + zinc supplementation was also associated with 40 % lower risk of severe ALRI in less well-nourished infants . MM supplementation was associated with a 15 % higher risk of diarrhea in all infants and 22 % higher risk in less well-nourished infants . Intermittent simultaneous supplementation with iron + zinc seems promising ; it will be useful to determine whether higher doses would provide greater benefits ABSTRACT : Erythrocyte superoxide dismutase ( ESOD ) activity reflects copper utilization and the risk of copper deficiency . To investigate the possible effects of inorganic iron on the metabolism of copper in low birth weight infants , we have measured ESOD activities in three groups of infants receiving different iron supplements . Fifty-five low birth weight infants were r and omly assigned to receive daily from 28 d either 13.8 mg ( HiFe ) , 7 mg ( MidFe ) , or no elemental iron ( NatFe ) as iron edetate . At 27 d , 8 , 12 , and 20 wk postnatal age , infants were weighed and measured and hematologic indices , plasma ferritin , zinc , and copper concentrations , and ESOD activities were assayed . Anthropometrical and hematologic indices and plasma copper and zinc concentrations did not differ among treatment groups at any time , but at 20 wk , plasma ferritin concentrations [ ( μg/L ) mean ; SD ] were lower in the NatFe group ( 17 ; 2.0 ) than in the HiFe group ( 32 ; 1.9 : 95 % confidence interval for mean difference 6.6 to 22.0 , p < 0.01 ) . ESOD activities ( U/g Hb ) were similar in HiFe ( 1447 ; 263 ) , MidFe ( 1552 ; 322 ) , and NatFe ( 1538 ; 382 ) groups at 27 d , but by 20 wk activities in the HiFe group ( 1537 ; 211 ) were lower than in the MidFe ( 1789 ; 403:95 % confidence interval 38 to 466 , p < 0.05 ) and NatFe ( 1858 ; 304 : 95 % confidence interval 150 to 492 , p < 0.01 ) groups . The lower ESOD activities found in the HiFe group at 20 wk may reflect altered copper metabolism induced by the iron supplement , but the clinical importance of this observation is unknown IMPORTANCE In sub-Saharan Africa , malaria is a leading cause of childhood morbidity and iron deficiency is among the most prevalent nutritional deficiencies . In 2006 , the World Health Organization and the United Nations Children 's Fund released a joint statement that recommended limiting use of iron supplements ( tablets or liquids ) among children in malaria-endemic areas because of concern about increased malaria risk . As a result , anemia control programs were either not initiated or stopped in these areas . OBJECTIVE To determine the effect of providing a micronutrient powder ( MNP ) with or without iron on the incidence of malaria among children living in a high malaria-burden area . DESIGN , SETTING , AND PARTICIPANTS Double-blind , cluster r and omized trial of children aged 6 to 35 months ( n = 1958 living in 1552 clusters ) conducted over 6 months in 2010 in a rural community setting in central Ghana , West Africa . A cluster was defined as a compound including 1 or more households . Children were excluded if iron supplement use occurred within the past 6 months , they had severe anemia ( hemoglobin level < 7 g/dL ) , or severe wasting ( weight-for-length z score < -3 ) . INTERVENTIONS Children were r and omized by cluster to receive a MNP with iron ( iron group ; 12.5 mg/d of iron ) or without iron ( no iron group ) . The MNP with and without iron were added to semiliquid home-prepared foods daily for 5 months followed by 1-month of further monitoring . Insecticide-treated bed nets were provided at enrollment , as well as malaria treatment when indicated . MAIN OUTCOMES AND MEASURES Malaria episodes in the iron group compared with the no iron group during the 5-month intervention period . RESULTS In intention-to-treat analyses , malaria incidence overall was significantly lower in the iron group compared with the no iron group ( 76.1 and 86.1 episodes/100 child-years , respectively ; risk ratio ( RR ) , 0.87 [ 95 % CI , 0.79 - 0.97 ] ) , and during the intervention period ( 79.4 and 90.7 episodes/100 child-years , respectively ; RR , 0.87 [ 95 % CI , 0.78 - 0.96 ] ) . In secondary analyses , these differences were no longer statistically significant after adjusting for baseline iron deficiency and anemia status overall ( adjusted RR , 0.87 ; 95 % CI , 0.75 - 1.01 ) and during the intervention period ( adjusted RR , 0.86 ; 95 % CI , 0.74 - 1.00 ) . CONCLUSION AND RELEVANCE In a malaria-endemic setting in which insecticide-treated bed nets were provided and appropriate malaria treatment was available , daily use of a MNP with iron did not result in an increased incidence of malaria among young children . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01001871 Objectives : To assess and compare efficacy of two micronutrient sprinkle supplementation on growth , anemia , and iron deficiency in Cambodian infants . Methods : A total of 204 infants aged 6 months and living in Kompong Chhnang Province , Cambodia were r and omly assigned to receive daily supplements of either iron ( 12.5 mg ) plus folic acid ( 150 & mgr;g ) plus zinc ( 5 mg ) ( MMN , n = 68 ) , or iron ( 12.5 mg ) plus folic acid ( 150 & mgr;g ) alone ( FFA , n = 68 ) , or placebo ( n = 68 ) for a 12 month period in powder form as sprinkles . Anthropometrics was evaluated bimonthly . Biochemical assessment was performed at baseline and at the end of intervention period . Results : At baseline , the overall mean ( SD ) of hemoglobin concentration was 101 g/L. No difference among groups was found for growth pattern . Significant decline was observed for weight-for-age and height-for-age z-scores in any group ( P < 0.0001 ) . The rate of recovery from anemia was significant ( P < 0.001 ) and comparable between MMN ( 54 % ) and FFA ( 53 % ) groups and higher than in the placebo group ( 22 % , P < 0.0001 ) . Through the study period , no significant change in the rate of iron deficiency was found in MMN and FFA groups , whereas it increased in the placebo group ( 31 % , baseline vs. 52 % , end of study ; P < 0.0001 ) . Conclusion : Both MMN and FFA supplements were effective for preventing or treating anemia in Cambodian infants and stabilizing plasma levels of ferritin . Use of micronutrients in a controlled home setting , as sprinkled daily supplements , may be promising in preventing and treating anemia in developing countries The behavioral effects of iron deficiency and its treatment were evaluated in a double-blind r and omized controlled community-based study of 191 Costa Rican infants , 12 to 23 months of age , with various degrees of iron deficiency . The Bayley Scales of Infant Development were administered before and both 1 week and 3 months after IM or oral administration of iron . Appropriate placebo-treated control infants were also tested . Infants with iron deficiency anemia showed significantly lower mental and motor test scores , even after considering factors relating to birth , nutrition , family background , parental IQ , and the home environment . After 1 week , neither IM nor oral iron treatments differed from placebo treatment in effects on scores . After 3 months , lower mental and motor test scores were no longer observed among iron-deficient anemic infants whose anemia and iron deficiency were both corrected ( 36 % ) . However , significantly lower mental and motor test scores persisted among the majority of initially anemic infants ( 64 % ) who had more severe or chronic iron deficiency . Although no longer anemic , they still showed biochemical evidence of iron deficiency after 3 months of treatment . These persistent lower scores suggest either that iron therapy adequate for correcting anemia is insufficient to reverse behavioral and developmental disturbances in many infants or that certain ill effects are long-lasting , depending on the timing , severity , or chronicity of iron deficiency anemia in infancy Whether children with malarial anaemia should receive supplementation with iron or folic acid is uncertain . Therefore , the effects of supplementary treatment with iron or folic acid , given together with chloroquine or pyrimethamine-sulfadoxine ( Fansidar ) , has been assessed in 600 Gambian children with uncomplicated falciparum malaria . After one month , haematological recovery was significantly better in the group treated with Fansidar than in the chloroquine-treated group ( difference in mean haemoglobin level = 0.54 g/dL , P = 0.01 ) . Children who received iron had a significantly better response than those given placebo ( differences in mean haemoglobin level after one month and at dry season follow-up = 0.70 g/dL , P = 0.006 , and 0.81 g/dL , P = 0.001 , respectively ) . Iron supplementation was not associated with increased prevalence of malaria . Supplementation with folic acid did not improve the haematological response but , among children who received Fansidar , the treatment failure rate was significantly higher among those given folic acid than among those given placebo . Thus , supplementation with iron , but not folic acid , improves haematological recovery without increasing susceptibility to malaria OBJECTIVE To compare the effectiveness of microencapsulated iron(II ) fumarate sprinkles ( with and without vitamin A ) , iron(II ) sulfate drops , and placebo sprinkles in preventing recurrence of anaemia and to determine the long-term haematological outcomes in children at high risk of recurrence of anaemia 12 months after the end of supplementation . METHODS A prospect i ve , r and omized , placebo-controlled design was used to study 437 Ghanaian children aged 8 - 20 months who were not anaemic ( haemoglobin > or = 100 g/l ) . Four groups were given microencapsulated iron(II ) fumarate sprinkles , microencapsulated iron(II ) fumarate sprinkles with vitamin A , iron(II ) sulfate drops or placebo sprinkles daily for six months . Primary outcome measures were change in haemoglobin and anaemic status at baseline and study end . Non-anaemic children at the end of the supplementation period were reassessed 12 months after supplementation ended . FINDINGS Overall , 324 children completed the supplementation period . Among the four groups , no significant changes were seen in mean haemoglobin , ferritin or serum retinol values from baseline to the end of the supplementation period . During the trial , 82.4 % ( 267/324 ) of children maintained their non-anaemic status . Sprinkles were well accepted without complications . At 12 months post-supplementation , 77.1 % ( 162/210 ) of children with no intervention remained non-anaemic . This proportion was similar for children among the four groups . CONCLUSION In most children previously treated for anaemia , further supplementation was not needed to maintain their non-anaemic status . These results may have important implication s for community intervention programmes in which initial high-dose treatment is needed because of a high prevalence of anaemia OBJECTIVE To assess the efficacy of micronutrient fortified sugar c and ies in improving the iron and vitamin A status in children aged 3 to 6 years . DESIGN Triple blind r and omized controlled trial . SETTING S Anganwadis and preparatory schools in rural Haryana . METHODS 410 children were r and omized in four groups . One group received full dose c and y ( vitamin A 1000 IU and 14 mg elemental iron ) daily , the second group received full dose c and y for 3 days a week , the third group received half dose c and y ( vitamin A 500 IU and 7 mg elemental iron ) daily and the fourth received placebo . The c and ies were provided to children under supervision of field workers . Hemoglobin , S. ferritin , S. retinol and S. retinol binding protein levels were estimated at baseline and after 13 weeks of intervention . RESULTS The increase in hemoglobin was least in the placebo group ( 0.3 g/dL ) as compared to the two full dose groups ( 1.15 - 1.18 g/dL , P < 0.001 ) . Among anemic children , the increase in hemoglobin was about 2 g/dL in the full dose group and 0.7 g/dL in the placebo group ( P < 0.001 ) . S. ferritin levels increased significantly only in the full dose daily group ( p < 0.05 ) . The prevalence of anemia decreased from around 50 % at baseline to 9.6 % in the full dose daily group ( p < 0.01 ) . Based on the S. retinol levels , the study area was not vitamin A deficient and the intervention did not result in a significant improvement in the vitamin A status of the children . CONCLUSION Micronutrient fortified c and ies were effective in improving the hemoglobin level and decreasing anemia prevalence . It could serve as a suitable vehicle for micronutrient supplementation in children and other target groups The effect of iron fortification is generally assumed to be less than iron supplementation ; however , the magnitude of difference in effects is not known . The present study aims to compare the efficacy of these two strategies on anaemia and iron status . After screening on low Hb , 425 anaemic children in six primary schools in Tam Nong district of Phu Tho province were included in a r and omized , placebo-controlled trial comparing two groups receiving iron fortified instant noodles or iron supplementation for 6 months and a control group , with children in all groups having been dewormed . Blood sample s were collected before and after intervention for haemoglobin , serum ferritin ( SF ) , serum transferrin receptor ( TfR ) , C-reactive protein ( CRP ) , and haemoglobinopathies analysis . Regression analysis was used to assess the effect of iron fortification and iron supplementation on haemoglobin concentration , SF , TfR , body iron , and anaemic status as outcome variables . The improvement of haemoglobin , SF , and body iron level in the group receiving iron fortification was 42 % ( 2.6 g/L versus 6.2 g/L ) , 20 % ( 23.5 μg/L versus 117.3 μg/L ) , and 31.3 % ( 1.4 mg/kg versus 4.4 mg/kg ) of that in the iron supplementation group . The prevalence of anaemia dropped to 15.1 % in the control group , with an additional reduction of anaemia of 8.5 % in the iron supplementation group . The additional reduction due to iron fortification was 5.4 % , which amounts to well over 50 % of the impact of supplementation . In conclusion , the efficacy of iron fortification based on reduction of prevalence of anaemia , and on the change in haemoglobin level , is about half of the maximum impact of supplementation in case of optimal compliance . Thus , in a population of anaemic children with mild iron deficiency , iron fortification should be the preferred strategy to combat anaemia To assess the efficacy and acceptability of a daily and intermittent iron supplementation , a double-blind , placebo-controlled trial was conducted in a public school located in periurban Lima , Peru . Adolescent girls ( n = 312 ) , 12 - 18 y old , were r and omly assigned to one of the following three groups : 1 ) 60 mg iron as ferrous sulfate daily from Monday to Friday ; 2 ) 60 mg iron as ferrous sulfate 2 d/wk and 3 d placebo ( intermittent ) ; 3 ) placebo , from Monday to Friday . Field workers gave the girls supplements during school hours for 17 wk ; 296 girls completed the trial . Girls took 94 % of the expected dose of 85 pills . Few side effects were reported . Postintervention , hemoglobin ( Hb ) , serum ferritin ( SF ) and free erythrocyte protoporphyrin ( FEP ) were improved significantly in the iron-supplemented groups compared with placebo ( P<0.05 ) . Daily supplements led to higher Hb increases than intermittent supplements ( P<0.05 ) , but SF and FEP were similar between the two groups . Thus , both iron supplementation schedules were efficacious in preventing iron deficiency in adolescent girls through the school system , and the daily schedule was better than the intermittent schedule at increasing Hb values and reducing anemia The effect of long-term oral iron supplementation on morbidity due to diarrhea , dysentery and respiratory infections in 349 children , aged 2 - 48 mo , living in a poor community of Bangladesh , was evaluated in this double-blind study . The treatment group received 125 mg of ferrous gluconate ( 15 mg elemental iron ) plus multivitamins and the controls received only multivitamins , daily for 15 mo . House-to-house visits were made on alternate days by trained community health workers for recording symptoms and duration of illnesses and for monitoring medicine intake . Seventy-six percent of the children continued the syrup for over 1 y. No untoward effects were noticed in either treatment group . The attack rates for diarrhea , dysentery and acute respiratory tract infections ( ARI ) were 3 , 3 and 5 episodes per child per year , respectively . Each episode of diarrhea lasted a mean of 3 d , and those of dysentery and ARI , 5 d. The two treatment groups did not differ in the number of episodes , mean duration of each episode , or total days of illnesses due to diarrhea , dysentery and ARI . However , a 49 % greater number of episodes of dysentery was observed with iron supplementation in a subset of the study children who were less than 12 mo old ( P = 0.03 ) . The results of this study suggest that long-term oral iron supplementation is not harmful for older children in a poor community . Further studies are needed to demonstrate the safety and efficacy of iron administration in young infants Objectives : To determine the effect of low-dose weekly supplementation with iron , zinc or both on growth of infants from 6 to 12 months of age . Subjects/ Methods : A total of 645 breastfed infants age 6 months who were not severely anemic ( Hb⩾90 g l−1 ) or severely malnourished ( weight-for-age ⩾60 % median ) were r and omized to receive 20 mg iron and 1 mg riboflavin ; 20 mg zinc and 1 mg riboflavin ; 20 mg iron , 20 mg zinc and 1 mg riboflavin ; or riboflavin alone ( control ) weekly for 6 months . Results : Baseline characteristics were similar among the four supplementation groups . Weight , length and mid-upper arm circumference were assessed at baseline , 8 , 10 and 12 months of age . There was no interaction of iron and zinc when given in a combined supplement on either weight or length ( P>0.05 ) . There were no effects of either iron or zinc on the rate of length or weight gain for all infants or when stratified by baseline Hb concentration . Conclusions : Weekly supplementation of 20 mg Fe , 20 mg Zn , or both does not benefit growth among infants 6–12 months of age in rural Bangladesh , a region with high rates of anemia and zinc deficiency BACKGROUND Clinical malaria and severe anaemia are major causes of paediatric hospital admission and death in many malaria-endemic setting s. In the absence of an effective and affordable vaccine , control programmes continue to rely on case management while attempting the large-scale deployment of insecticide-treated nets . We did a r and omised , placebo-controlled trial to assess the efficacy and safety of intermittent sulphadoxine-pyrimethamine treatment on the rate of malaria and severe anaemia in infants in a rural area of Tanzania . METHODS We r and omly assigned 701 children living in Ifakara , southern Tanzania , sulphadoxine-pyrimethamine or placebo at 2 , 3 , and 9 months of age . All children received iron supplementation between 2 and 6 months of age . The intervention was given alongside routine vaccinations delivered through WHO 's Exp and ed Program on Immunisation ( EPI ) . The primary outcome measures were first or only episode of clinical malaria , and severe anaemia in the period from recruitment to 1 year of age . Morbidity monitoring through a hospital-based passive case-detection system was complemented by cross-sectional surveys at 12 and 18 months of age . Results were expressed in terms of protective efficacy ( 100 [ 1-hazard ratio]% ) and analysis was by intention to treat . FINDINGS 40 children dropped out ( 16 died , 11 migrated , 12 parents withdrew consent , and one for other reasons ) . Intermittent sulphadoxine-pyrimethamine treatment was well tolerated and no drug-attributable adverse events were recorded . During the first year of life , the rate of clinical malaria ( events per person-year at risk ) was 0.15 in the sulphadoxine-pyrimethamine group versus 0.36 in the placebo group ( protective efficacy 59 % [ 95 % CI 41 - 72 ] ) , and the rate of severe anaemia was 0.06 in the sulphadoxine-pyrimethamine group versus 0.11 in the placebo group ( 50 % [ 8 - 73 ] ) . Serological responses to EPI vaccines were not affected by the intervention . INTERPRETATION This new approach to malaria control reduced the rate of clinical malaria and severe anaemia by delivering an available and affordable drug through the existing EPI system . Data are urgently needed to assess the potential cost-effectiveness of intermittent treatment in areas with different patterns of malaria endemicity The effect of iron therapy on malarial infection was investigated in Papua New Guinea , where malaria is endemic . Prepubescent schoolchildren with hemoglobin levels of 8 - 12 g/dl were r and omly assigned to receive either 200 mg ferrous sulfate or a placebo twice daily for 16 weeks . Iron status and malarial infection were assessed at baseline , after 6 and 16 weeks of therapy , and 8 weeks after therapy was discontinued . Iron status was significantly improved by the treatment . The treatment did not significantly affect parasite rate , parasite density , or levels of anti-malarial IgG. No changes in spleen size were observed in either group . Furthermore , there was no significant difference between the groups in reported episodes of suspected malaria during the therapy . These results suggest that , in malaria endemic areas , oral treatment for iron deficiency can be carried out in semi-immune or immune schoolchildren without adverse consequences Objective : To assess the effects of iron and deworming on linear growth performance of preschoolers . Design : Three-month r and omized , double-blind and placebo-controlled trial . The children were allocated to four treatments : iron ( 60 mg elemental iron/day)+albendazole ( 200 mg/day for 3 consecutive days , repeated 1 month later ) , iron+albendazole-placebo , albendazole+iron-placebo or placebos . The supplementation was supervised . Subjects : A group of 177 children aged 3–5 y was selected from low-income households in a rural area in southern Bénin . A complete data set was analysed for 140 subjects . Many children were stunted ( 58 % had height-for-age Z-score < −2 ) , none were wasted ( 2 % had weight-for-height Z-score < −2 ) and 76 % were anemic ( Hb<110 g/l).Main outcome measures : Anthropometric parameters , hemoglobin and eggs per gram feces . Results : No significant difference in changes in anthropometric parameters was observed between study groups , and also not in a sub- sample of stunted and anemic subjects . Changes in hemoglobin were highest in the iron-treated subjects at the end of the 3-month intervention period ( P=0.032 ) . The difference between the iron and the placebo groups remained significant even 7 months later ( P=0.022 ) . The difference was 5 g/l in both periods . Ascaris lumbricoides and hookworm infections decreased significantly in albendazole-treated subjects ( P<0.05 ) . Conclusions : In addition to recurrent parasitic infection burden , the children may have multiple micronutrient deficiencies . Therefore , it may be interesting to study appetite and food intake of young toddlers in relation to health and linear growth performance in poor environments . Sponsorship : The Nestlé Foundation ( Lausanne , Switzerl and ) .European Journal of Clinical Nutrition ( 2001 ) 55 , During a r and omized placebo-controlled trial of chemoprophylaxis against Plasmodium falciparum malaria and iron supplementation , in infants living under conditions of intense transmission , all sample s of P. falciparum obtained from children aged 5 and 8 months were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis for the msp2 locus . One hundred and six blood sample s were analysed for the number of concurrent infections ( multiplicity ) , and the allelic family of each msp2 genotype was determined . Mean multiplicity of infection was , overall , 2.76 infections/child , and it was significantly reduced in infants receiving chemoprophylaxis . This finding might help to explain the rebound effect in morbidity observed after prophylaxis was ended . Iron supplementation did not affect multiplicity of infection . In infants receiving placebo only , or placebo and iron supplementation , a significant positive association was observed between the number of infections and parasite densities ( Spearman 's p = 0.25 , P-0.047 ) . This association was lost in the group receiving chemoprophylaxis alone , or in combination with iron . This study showed a significant association of FC27-like msp2 alleles with prospect i ve risk of clinical malaria in children ( relative risk = 1.487 , P = 0.013 ) . Such an association was also found for the present risk of clinical malaria in infants receiving prophylaxis ( odds ratio = 3.84 , P = 0.026 ) , which might imply that chemoprophylaxis may impair the development of premunition BACKGROUND Studies from Asia have suggested that zinc supplementation can reduce morbidity and mortality in children , but evidence from malarious population s in Africa has been inconsistent . Our aim was to assess the effects of zinc supplementation on overall mortality in children in Pemba , Zanzibar . METHODS We enrolled 42,546 children aged 1 - 36 months , contributing a total of 56,507 child-years in a r and omised , double-blind , placebo-controlled trial in Pemba , Zanzibar . R and omisation was by household . 21 274 children received daily supplementation with zinc 10 mg ( 5 mg in children younger than 12 months ) for mean 484.7 days ( SD 306.6 ) . 21,272 received placebo . The primary endpoint was overall mortality , and analysis was by intention to treat . This study is registered as an International St and ard R and omised Clinical Trial , number IS RCT N59549825 . FINDINGS Overall , there was a non-significant 7 % ( 95 % CI -6 % to 19 % ; p=0.29 ) reduction in the relative risk of all-cause mortality associated with zinc supplementation . INTERPRETATION We believe that a meta- analysis of all studies of mortality and morbidity , will help to make evidence -based recommendations for the role of zinc supplementation in public health policy to improve mortality , morbidity , growth , and development in young children A controlled trial of iron dextran prophylaxis in infants 2 months old was carried out on the north coast of New Guinea , where malaria is holoendemic . These infants have a high carrier rate ( 80 % ) for alpha + thalassaemia . The neighbouring highl and area has a low rate of both malaria and alpha + thalassaemia . The results of clinical and haematological examination of these infants at 6 and 12 months were analysed to determine the relationship between alpha thalassaemia and susceptibility to malaria . Infants were divided according to haemoglobin Bart 's levels found at birth into 3 groups corresponding to probable genotypes . Homozygotes had higher slide malarial positivity and spleen rates at 6 and 12 month than the normal or heterozygote groups . Analysis of variance of haemoglobin levels showed that the anaemia associated with malaria was greatest in the normals and least in the homozygotes at 6 months . A possible protective mechanism of alpha thalassaemia is discussed BACKGROUND & AIMS We investigated Helicobacter pylori ( H pylori)-infection as a cause of iron deficiency ( ID ) and iron-deficiency anemia ( IDA ) or treatment failure of iron supplementation . METHODS We r and omized 200 Hp-infected children ( positive urea breath test ) 2 - 5 years of age with IDA ( hemoglobin level < 110 g/L ; serum ferritin level < 12 microg/L ; and soluble transferrin receptor > 8.3 mg/L ) or ID ( serum ferritin level < 12 microg/L or soluble transferrin receptor level > 8.3 mg/L ) to 1 of 4 regimens : 2-week anti-Hp therapy ( amoxicillin , clarithromycin , and omeprazole ) plus 90-day oral ferrous sulfate ( anti-Hp plus iron ) , 2-week anti-Hp therapy alone , 90-day oral iron alone , or placebo . Sixty noninfected children with IDA received iron treatment as negative control . RESULTS Hp-infected children receiving iron had significantly less frequent treatment failure compared with those with no iron in correcting IDA ( 11 % [ 95 % confidence interval ( CI ) , 2%-20 % ] for anti-Hp plus iron , 0 % for iron alone vs 33 % [ 95 % CI , 26%-46 % ] for anti-Hp and 45 % [ 95 % CI , 31%-59 % ] for placebo ; chi(2 ) = 127 ; P < .0001 ) , ID ( 19 % [ 95 % CI , 8%-30 % ] for anti-Hp plus iron , 7 % [ 95 % CI , 0%-14 % ] for iron alone vs 65 % [ 95 % CI , 52%-78 % ] for anti-Hp alone , and 78 % [ 95 % CI , 66%-90 % ] for placebo ; chi(2 ) = 124 ; P < .0001 ) , or anemia ( 34 % [ 95 % CI , 20%-40 % ] for anti-Hp plus iron , 27 % [ 95 % CI , 14%-40 % ] for iron alone vs 65 % [ 95 % CI , 52%-78 % ] for anti-Hp alone and 78 % [ 95 % CI , 66%-90 % ] for placebo ; chi(2 ) = 46 ; P < .0001 ) . Cure rates of IDA , ID , or anemia with iron were comparable with that of the negative control group . Improvements in iron status also were significantly greater in groups with iron . CONCLUSIONS H pylori is neither a cause of IDA/ID nor a reason for treatment failure of iron supplementation in young Bangladeshi children Tested 47 first-year primary school children at a mission school in rural Zaire for cognitive ability with the Kaufman Assessment Battery for Children ( K-ABC ) adopted to the language of Kituba . Within a day of this test , each child was evaluated for blood hemoglobin ( Hgb ) level and the presence of intestinal parasites . Half of the children received an iron supplement ( 20 mg Fe ) for 30 days and those children positive for the intestinal parasites of ankylostome or ascaris were r and omly selected to receive either a vermifuge treatment or placebo . All of the children were again evaluated medically and cognitively 4 weeks after the initiation of treatment . Using discriminant analysis , performance on the Mental Processing Composite of the K-ABC 1 month after treatment in combination with increases in blood Hgb result ed in the successful classification of 74 % in terms whether a child had received both iron supplement and vermifuge treatment ( p = .007 ) . With respect to our home evaluation for each child , factors related to the nutritional and economic well-being of the home environment proved a reliable marker for Simultaneous Processing ability . However , the present findings also suggest that over the short-term , changes in blood Hgb that accompany both vermifuge and iron supplement treatment together can improve certain aspects of cognitive ability , perhaps by means of heightened attentional capacity Summary Background Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa . Quinine is still the established treatment of choice , although evidence from Asia suggests that artesunate is associated with a lower mortality . We compared parenteral treatment with either artesunate or quinine in African children with severe malaria . Methods This open-label , r and omised trial was undertaken in 11 centres in nine African countries . Children ( < 15 years ) with severe falciparum malaria were r and omly assigned to parenteral artesunate or parenteral quinine . R and omisation was in blocks of 20 , with study numbers corresponding to treatment allocations kept inside opaque sealed paper envelopes . The trial was open label at each site , and none of the investigators or trialists , apart from for the trial statistician , had access to the summaries of treatment allocations . The primary outcome measure was in-hospital mortality , analysed by intention to treat . This trial is registered , number IS RCT N50258054 . Findings 5425 children were enrolled ; 2712 were assigned to artesunate and 2713 to quinine . All patients were analysed for the primary outcome . 230 ( 8·5 % ) patients assigned to artesunate treatment died compared with 297 ( 10·9 % ) assigned to quinine treatment ( odds ratio [ OR ] stratified for study site 0·75 , 95 % CI 0·63–0·90 ; relative reduction 22·5 % , 95 % CI 8·1–36·9 ; p=0·0022 ) . Incidence of neurological sequelae did not differ significantly between groups , but the development of coma ( 65/1832 [ 3·5 % ] with artesunate vs 91/1768 [ 5·1 % ] with quinine ; OR 0·69 95 % CI 0·49–0·95 ; p=0·0231 ) , convulsions ( 224/2712 [ 8·3 % ] vs 273/2713 [ 10·1 % ] ; OR 0·80 , 0·66–0·97 ; p=0·0199 ) , and deterioration of the coma score ( 166/2712 [ 6·1 % ] vs 208/2713 [ 7·7 % ] ; OR 0·78 , 0·64–0·97 ; p=0·0245 ) were all significantly less frequent in artesunate recipients than in quinine recipients . Post-treatment hypoglycaemia was also less frequent in patients assigned to artesunate than in those assigned to quinine ( 48/2712 [ 1·8 % ] vs 75/2713 [ 2·8 % ] ; OR 0·63 , 0·43–0·91 ; p=0·0134 ) . Artesunate was well tolerated , with no serious drug-related adverse effects . Interpretation Artesunate substantially reduces mortality in African children with severe malaria . These data , together with a meta- analysis of all trials comparing artesunate and quinine , strongly suggest that parenteral artesunate should replace quinine as the treatment of choice for severe falciparum malaria worldwide . Funding The Wellcome Trust The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas OBJECTIVE This study analyses the impact of weekly iron supplementation with ferrous sulphate heptahydrate ( FeSO4 ) in 5-year-olds compared with placebo , on hemoglobin ( Hb ) and hematocrit ( Ht ) values and anemia . DESIGN The study concerns a cluster-r and omized , placebo-controlled double-blind trial . Intervention participants received 50 mg elemental iron for 14 weeks . SETTING The study population comprised pre-school children ( n = 135 ) from one r and omly chosen public school in the northeast of Brazil . SUBJECTS Participants were 5-year-old students from a public school . RESULTS Mean Hb and Ht values increased after iron supplementation , with p < 0.0001 . There was no statistically significant increase in the placebo group . After intervention , anemia prevalence reduced only in the intervention group , from 48.0 % to 26.0 % . CONCLUSIONS Weekly iron supplementation was effective in reducing anemia in 5-year-olds The effects of oral iron supplementation on blood iron levels and learning achievement in 130 rural Indonesian school children were assessed in this double-blind study . The children were classified into anemic and nonanemic groups according to their initial hemoglobin and transferrin saturation levels and were r and omly assigned to either iron or placebo treatment for 3 mo . Hematological , anthropometric , and learning-achievement data were collected before ( T1 ) and after ( T2 ) the treatment period and 3 mo later . The means and st and ard deviations suggest that supplementation with 10 mg ferrous sulfate per kilogram body weight per day for 3 mo result ed in an apparent improvement in anemic subjects ' hematological status and learning-achievement scores . No tests of statistical comparisons are reported Iron deficiency and anemia remain among the most important global public health problems facing school children . Helminth infections often peak at school age and aggravate nutritional risks . We conducted a 12-wk r and omized controlled trial in 406 Malian anemic schoolchildren infected with Schistosoma hematobium to examine the effects of 2 doses of praziquantel ( P ) ( 40 mg/kg body weight ) , P + 60 mg/d iron ( Fe ) , and /or a multiple micronutrient supplement ( MM ) that included 18 mg/d Fe . Supplements were administered to the children each school day ( 5 d/wk ) throughout the study . Changes in hemoglobin ( Hb ) , serum ferritin ( SF ) , and serum transferrin receptors ( s-TfR ) were followed . We also examined interactions between Fe and MM supplements on Hb and SF concentrations and malaria incidence . The effects of Fe on Hb and SF concentrations were greater than the effects of P alone and MM with or without added Fe at 6 and 12 wk ( P < 0.001 ) . In all groups , s-TfR decreased at 6 and 12 wk compared with baseline . The decrease was most pronounced in the P + Fe group compared with the other 3 groups at wk 6 ( P = 0.05 ) . Fe and MM interacted negatively at wk 6 and 12 to affect Hb ( beta = -0.43 , 95 % CI = -0.77 , -0.09 ; P = 0.01 and beta = -0.47 , 95 % CI = -0.83 , -0.11 ; P = 0.01 , respectively ) and SF ( beta = -0.42 , 95 % CI = -25.60 , 12.31 ; P < 0.001 , and beta = -0.37 , 95 % CI = -0.63 , -0.12 ; P = 0.004 , respectively ) . Malaria incidence was higher in the groups treated with added Fe ( relative risk : 1.66 ; 95 % CI : 0.75 , 3.67 ) . In this context , MM with added iron were not more effective than Fe without MM . Fe supplementation of schoolchildren with 60 mg/d for anemia control should be considered carefully The effects of iron deficiency on immunity remain controversial . This study was design ed to assess the impact of iron supplementation on the immune status , in 81 children aged 6 months–3 years , at high risk for iron deficiency , using a longitudinal double blind r and omised and placebo-controlled study . Lymphocytes of iron-deficient children produced less interleukin-2 in vitro . Iron supplementation for 2 months increased mean corpuscular volume , serum ferritin and serum transferrin , but had no effect on the parameters of T-cell mediated immunity . The lower interleukin-2 levels in iron-deficient suggest that cell-mediated immunity may be impaired in iron deficiency Iron supplementation has been suggested as a strategy for prevention and treatment of iron deficiency ( ID ) and iron deficiency anemia ( IDA ) in many countries , but non-compliance of daily regimens and common dosage remain as major challenges . The aim of this study was to investigate the effects of low dose once weekly iron supplementation in adolescent girls . The study was design ed as a community-based , r and omized , supplementation trial . The initial sample consisted of 200 female high school students , aged 14–16 years old , of whom 193 students concluded the study . They were r and omly selected and assigned into either iron-supplemented group ( ISG ) or iron-unsupplemented group ( IUG ) . The ISG received 150 mg ferrous sulfate once weekly for 16 weeks , whereas the IUG received nothing . Weight , height , and hematological parameters were measured and compared between the two groups before and after the intervention . There was no significant difference between the initial measures of the two groups before the intervention . After 16 weeks of intervention , mean of hemoglobin and serum ferritin improved significantly in ISG compared to IUG . At the beginning of the study , percent of anemia , IDA , and ID in ISG were 12.5 % , 8.3 % , and 30.2 % , whereas these figures for IUG in this period of study were 14.4 , 10.3 , and 38.2 , respectively , which were not significantly different between the two groups . However , percentages of the above items at the end of study in ISG were 2.1 % , 0 % , and 21.9 % , respectively . In contrast to IUG , all cases of IDA were abolished in the ISG . Our study showed that once weekly supplementation of 150 mg ferrous sulfate for 16 weeks significantly improved iron status in female adolescents and effectively treated IDA . There is no need for higher dosage of iron for supplementation that may cause adverse effects and bear higher costs Micronutrient powders ( MNP ) are often added to complementary foods high in inhibitors of iron and zinc absorption . Most MNP therefore include high amounts of iron and zinc , but it is no longer recommended in malarial areas to use untargeted MNP that contain the Reference Nutrient Intake for iron in a single serving . The aim was to test the efficacy of a low-iron and -zinc ( each 2.5 mg ) MNP containing iron as NaFeEDTA , ascorbic acid ( AA ) , and an exogenous phytase active at gut pH. In a double-blind controlled trial , South African school children with low iron status ( n = 200 ) were r and omized to receive either the MNP or the unfortified carrier added just before consumption to a high-phytate maize porridge 5 d/wk for 23 wk ; primary outcomes were iron and zinc status and a secondary outcome was somatic growth . Compared with the control , the MNP increased serum ferritin ( P < 0.05 ) , body iron stores ( P < 0.01 ) and weight-for-age Z-scores ( P < 0.05 ) and decreased transferrin receptor ( P < 0.05 ) . The prevalence of iron deficiency fell by 30.6 % ( P < 0.01 ) and the prevalence of zinc deficiency decreased by 11.8 % ( P < 0.05 ) . Absorption of iron from the MNP was estimated to be 7 - 8 % . Inclusion of an exogenous phytase combined with NaFeEDTA and AA may allow a substantial reduction in the iron dose from existing MNP while still delivering adequate iron and zinc . In addition , the MNP is likely to enhance absorption of the high native iron content of complementary foods based on cereals and /or legumes A double-blind clinical trial was conducted in Indonesia to assess effects of iron supplementation on performance of iron-depleted and iron-deficient anemic children in discrimination and oddity learning tasks . Half these children received elemental Fe for 8 wk ; the others received a placebo . There were significant changes from pre- to postintervention evaluations in ferritin , transferrin saturation , free erythrocyte protoporphyrin , and hemoglobin among the anemic and iron-depleted children ; no changes were observed among the placebos or any of the iron-replete children . The magnitude of hematological changes in anemic children treated with iron was small ; yet , after treatment the children 's mean ferritin , transferrin saturation , and hemoglobin values were above the cutoff points used for the definition of iron-deficiency anemia ( IDA ) . Pre- and posttreatment psychological test data show that IDA produces alterations in cognitive processes related to visual attention and concept acquisition , alterations reversed with iron treatment BACKGROUND In sub-Saharan Africa , parasitic diseases and low bioavailable iron intake are major causes of anemia . Anemia results from inflammation , preventing iron recycling and decreasing dietary iron absorption . Hookworm , Plasmodium , and Schistosoma infections contribute to anemia , but their influence on dietary iron absorption and recycling is unknown . OBJECTIVE The objective was to measure inflammation biomarkers , hepcidin , iron absorption , and utilization pre- and posttreatment in children with afebrile malaria , hookworm , and Schistosoma haematobium infection . DESIGN Ivorian children aged 11 - 17 y with afebrile Plasmodium falciparum ( n = 17 ) , hookworm ( n = 16 ) , or S. haematobium infection ( n = 8) consumed a syrup containing 3 mg ⁵⁷Fe as ferrous sulfate and received an intravenous infusion of 50 μg ⁵⁸Fe as ferrous citrate . Children were treated for their respective infection , and the iron studies were repeated 4 wk later . Iron and inflammation biomarkers and hepcidin were measured . RESULTS Geometric mean iron absorptions in the afebrile malaria and hookworm groups were 12.9 % and 32.2 % ( P < 0.001 ) before treatment and 23.6 % and 30.0 % ( P = 0.113 ) after treatment , respectively . Treatment of afebrile malaria reduced inflammation ( P < 0.001 ) and serum hepcidin ( P = 0.004 ) and improved iron absorption ( P = 0.003 ) . Treatment of hookworm infection neither affected inflammation biomarkers nor altered iron absorption . Similarly , there was a lack of treatment effects in the S. haematobium-infected group ; however , the small sample size limits conclusions . Geometric mean iron utilization ranged between 79.1 % and 88.0 % in the afebrile malaria and hookworm groups with no significant differences pre- and posttreatment . CONCLUSIONS In school-age children , hookworm infection does not produce inflammation or increase serum hepcidin , and it does not influence iron absorption or utilization . In contrast , afebrile malaria causes inflammation , increases hepcidin , and reduces iron absorption but not utilization . These findings provide insights into the iron metabolism and the etiology of anemia in parasitic infections Background The period of complementary feeding , starting around 6 months of age , is a time of high risk for growth faltering and morbidity . Low micronutrient density of locally available foods is a common problem in low income countries . Children of HIV-infected women are especially vulnerable . Although antiretroviral prophylaxis can reduce breast milk HIV transmission in early infancy , there are no clear feeding guidelines for after 6 months . There is a need for acceptable , feasible , affordable , sustainable and safe ( AFASS by WHO terminology ) foods for both HIV-exposed and unexposed children after 6 months of age . Methods and Findings We conducted in Lusaka , Zambia , a r and omised double-blind trial of two locally made infant foods : porridges made of flour composed of maize , beans , bambaranuts and groundnuts . One flour contained a basal and the other a rich level of micronutrient fortification . Infants ( n = 743 ) aged 6 months were r and omised to receive either regime for 12 months . The primary outcome was stunting ( length-for-age Z<−2 ) at age 18 months . No significant differences were seen between trial arms overall in proportion stunted at 18 months ( adjusted odds ratio 0.87 ; 95 % CI 0.50 , 1.53 ; P = 0.63 ) , mean length-for-age Z score , or rate of hospital referral or death . Among children of HIV-infected mothers who breastfed < 6 months ( 53 % of HIV-infected mothers ) , the richly-fortified porridge increased length-for-age and reduced stunting ( adjusted odds ratio 0.17 ; 95 % CI 0.04 , 0.84 ; P = 0.03 ) . Rich fortification improved iron status at 18 months as measured by hemoglobin , ferritin and serum transferrin receptors . Conclusions In the whole study population , the rich micronutrient fortification did not reduce stunting or hospital referral but did improve iron status and reduce anemia . Importantly , in the infants of HIV-infected mothers who stopped breastfeeding before 6 months , the rich fortification improved linear growth . Provision of such fortified foods may benefit health of these high risk infants . Trial registration Controlled-Trials.com IS RCT Abstract Objective : To measure the effects of iron supplementation and anthelmintic treatment on iron status , anaemia , growth , morbidity , and development of children aged 6–59 months . Design : Double blind , placebo controlled r and omised factorial trial of iron supplementation and anthelmintic treatment . Setting : Community in Pemba Isl and , Zanzibar . Participants : 614 preschool children aged 6–59 months . Main outcome measures : Development of language and motor skills assessed by parental interview before and after treatment in age appropriate subgroups . Results : Before intervention , anaemia was prevalent and severe , and geohelminth infections were prevalent and light — Plasmodium falciparum infection was nearly universal . Iron supplementation significantly improved iron status , but not haemoglobin status . Iron supplementation improved language development by 0.8 ( 95 % confidence interval 0.2 to 1.4 ) points on the 20 point scale . Iron supplementation also improved motor development , but this effect was modified by baseline haemoglobin concentrations ( P=0.015 for interaction term ) and was apparent only in children with baseline haemoglobin concentrations < 90 g/l . In children with a baseline haemoglobin concentration of 68 g/l ( one st and ard deviation below the mean value ) , iron treatment increased scores by 1.1 ( 0.1 to 2.1 ) points on the 18 point motor scale . Mebendazole significantly reduced the number and severity of infections caused by Ascaris lumbricoides and Trichuris trichiura , but not by hookworms . Mebendazole increased development scores by 0.4 ( −0.3 to 1.1 ) points on the motor scale and 0.3 ( −0.3 to 0.9 ) points on the language scale . Conclusions : Iron supplementation improved motor and language development of preschool children in rural Africa . The effects of iron on motor development were limited to children with more severe anaemia ( baseline haemoglobin concentration < 90 g/l ) . Mebendazole had a positive effect on motor and language development , but this was not statistically significant . What is already known on this topic Iron is needed for development and functioning of the human brain Anaemic children show developmental delays , but it is not yet clear whether iron deficiency causes these deficits or whether iron supplementation can reverse them Helminth infections in schoolchildren are associated with cognitive deficits , but few studies have been made of helminth infection and early child development What this study adds Low doses of oral iron supplementation given daily improved language development in children aged 1–4 years in Zanzibar Iron supplementation improved motor development , but only in children with initial haemoglobin concentrations below 90 g/l The effects of routine anthelmintic treatment on motor and language milestones were positive , but non-significant , with our sample A r and omized , placebo-controlled treatment trial was conducted among 546 anemic ( hemoglobin concentration , 7 - 11 g/dL ) children aged 2 - 36 months in an area with intense malaria transmission in western Kenya . All children used bednets and received a single dose of sulfadoxine-pyrimethamine ( SP ) on enrollment , followed by either intermittent preventive treatment ( IPT ) with SP at 4 and 8 weeks and daily iron for 12 weeks , daily iron and IPT with SP placebo , IPT and daily iron placebo , or daily iron placebo and IPT with SP placebo ( double placebo ) . The mean hemoglobin concentration at 12 weeks , compared with that for the double-placebo group , was 1.14 g/dL ( 95 % confidence interval [ CI ] , 0.82 - 1.47 g/dL ) greater for the IPT+iron group , 0.79 g/dL ( 95 % CI , 0.46 - 1.10 g/dL ) greater for the iron group , and 0.17 g/dL ( 95 % CI , -0.15 - 0.49 g/dL ) greater for the IPT group . IPT reduced the incidence of malaria parasitemia and clinic visits , but iron did not . The combination of IPT and iron supplementation was most effective in the treatment of mild anemia . Although IPT prevented malaria , the hematological benefit it added to that of a single dose of SP and bednet use was modest BACKGROUND It is unknown whether iron supplementation in human immunodeficiency virus (HIV)-infected children living in regions with high infection pressure is safe or beneficial . A 2-arm , double-blind , r and omized , controlled trial was conducted to examine the effects of iron supplementation on hemoglobin , HIV disease progression , and morbidity . METHODS HIV-infected Malawian children aged 6 - 59 months with moderate anemia ( hemoglobin level , 7.0 - 9.9 g/dL ) were r and omly assigned to receive 3 mg/kg/day of elemental iron and multivitamins ( vitamins A , C , and D ) or multivitamins alone for 3 months . Participants were followed for 6 months . RESULTS A total of 209 children were r and omly assigned to treatment , and 196 ( 93.8 % ) completed 6 months of follow-up . Iron supplementation was associated with greater increases in hemoglobin concentrations ( adjusted mean difference [ aMD ] , 0.60 ; 95 % confidence interval [ CI ] , .06 - 1.13 ; P = .03 ) and reduced the risk of anemia persisting for up to 6 months follow-up ( adjusted prevalence ratio , 0.59 ; 95 % CI , .38-.92 ; P = .02 ) . Children who received iron had a better CD4 percentage response at 3 months ( aMD , 6.00 ; 95 % CI , 1.84 - 10.16 ; P = .005 ) but an increased incidence of malaria at 6 months ( incidence rate , 120.2 vs 71.7 ; adjusted incidence rate ratio [ aIRR ] , 1.81 [ 95 % CI , 1.04 - 3.16 ] ; P = .04 ) , especially during the first 3 months ( incidence rate , 78.1 vs 36.0 ; aIRR , 2.68 [ 95 % CI , 1.08 - 6.63 ] ; P = .03 ) . CONCLUSIONS Iron supplementation in anemic HIV-infected children has beneficial effects on hemoglobin , anemia , and immunity but increases the risk of malaria . Thus , iron supplementation in HIV-infected children living in malaria-endemic areas should only be provided in combination with adequate protection from malaria . CLINICAL TRIALS REGISTRATION IS RCT N-62947977 Abstract Objective To evaluate the effects of intermittent preventive treatment for malaria in infants ( IPTi ) with sulfadoxine-pyrimethamine in an area of intense , seasonal transmission . Design Cluster r and omised placebo controlled trial , with 96 clusters allocated r and omly to sulfadoxine-pyrimethamine or placebo in blocks of eight . Interventions Children received sulfadoxine-pyrimethamine or placebo and one month of iron supplementation when they received DPT-2 , DPT-3 , or measles vaccinations and at 12 months of age . Main outcome measures Incidence of malaria and of anaemia determined through passive case detection . Results 89 % ( 1103/1242 ) of children in the placebo group and 88 % ( 1088/1243 ) in the IPTi group completed follow-up to 24 months of age . The protective efficacy of IPTi against all episodes of malaria was 24.8 % ( 95 % confidence interval 14.3 % to 34.0 % ) up to 15 months of age . IPTi had no protective effect against malaria between 16 and 24 months of age ( protective efficacy −4.9 % , −21.3 % to 9.3 % ) . The incidence of high parasite density malaria ( ≥ 5000 parasites/μl ) was higher in the IPTi group than in the placebo group between 16 and 24 months of age ( protective efficacy −19.5 % , −39.8 % to −2.2 % ) . IPTi reduced hospital admissions with anaemia by 35.1 % ( 10.5 % to 52.9 % ) up to 15 months of age . IPTi had no significant effect on anaemia between 16 and 24 months of age ( protective efficacy −6.4 % , −76.8 % to 35.9 % ) . The relative risk of death up to 15 months of age in the IPTi group was 1.26 ( 95 % confidence interval 0.81 to 1.96 ; P = 0.31 ) , and from 16 to 24 months it was 1.28 ( 0.77 to 2.14 ; P = 0.35 ) . Conclusions Intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine can reduce malaria and anaemia in infants even in seasonal , high transmission areas , but concern exists about possible rebound in the incidence of malaria in the second year of life OBJECTIVE To test the efficacy of double-fortified salt ( DFS ) on the anaemia and iodine deficiency ( ID ) status of women and their children . DESIGN Double-blind r and omised controlled trial . SETTING Sekyere West District of Ghana . SUBJECTS In this eight-month trial , mildly anaemic or non-anaemic , non-pregnant , non-lactating women were r and omised into three groups receiving : DFS plus weekly placebo ( n = 61 ) ; iodised salt plus weekly 70 mg iron supplement ( n = 65 ) ; or iodised salt ( IS ) plus weekly placebo ( control group , n = 58 ) . Correspondingly , their mildly anaemic and non-anaemic children aged 1 - 5 years were r and omised into two groups receiving either the DFS ( n = 23 ) or IS alone ( control group , n = 59 ) . RESULTS At the end of the intervention , prevalence of anaemia in women remained unchanged in the DFS or IS plus weekly iron supplement group , but significantly increased by 19.5 % in the control group ( P = 0.039 ) . In children , prevalence of anaemia in the DFS group significantly decreased by 21.7 % ( P = 0.025 ) while no change was observed in the control group . ID decreased significantly in all groups of women ( P < 0.001 ) and children ( P < 0.05 ) , with no difference among groups of women and children . CONCLUSION While the use of DFS prevented anaemia in women , it had a significant role in both the prevention and treatment of anaemia in children . Both the DFS and IS significantly reduced ID in women and children to a similar degree Objectives : To examine the effect of low birth weight ( LBW ) and fetal anaemia ( FA ) on haemoglobin ( Hb ) patterns in infancy . To study the additional contribution of other risk factors known at birth . To examine the effect of iron supplementation during infancy on Hb levels . Methods : A stratified cohort of infants in Malawi ( 83 with LBW ( < 2500 g ) , 111 with FA ( cord Hb < 125 g/l ) , 31 with both LBW and FA , and 176 controls ) was followed during infancy . Hb levels were measured at about 2 , 4 , 6 , 9 , and 12 months of age . Repeated measures models were used to describe the changes in Hb levels over time . Results : The mean Hb concentration in the control group was 95.5 g/l ( 95 % confidence interval ( CI ) 92.5 to 98.5 ) at 2 months , 86.9 g/l ( 95 % CI 84.4 to 89.4 ) at 9 months , and 898 g/l ( 95 % CI 874 to 92.2 ) at 12 months . Differences between LBW infants and controls increased over time ( difference at 12 months : 5.5 g/l ( 95 % CI 1.3 to 9.7 ) ) . Infants with FA had borderline significantly lower Hb at 2 months ( p = 0.07 ) , but at 6 months their levels were similar to those of controls . The LBW infants and those with FA had the lowest Hb levels ( difference from controls at 12 months 7.9 g/l ) . Parity , placental and maternal malaria at delivery , and sex significantly affected Hb levels after adjustment for LBW and FA . After iron supplementation , Hb significantly increased . Conclusions : Antimalarial control and iron supplementation throughout pregnancy should be increased to reduce the incidence of infant anaemia and improve child development and survival Summary Background Recent data suggest that daily iron supplementation of iron-replete children could impair their growth . If verified for weekly iron supplementation these results would markedly complicate targeting and implementing school-based weekly iron supplementation programs . Aim of the study To ascertain the effect of weekly iron supplementation on the growth and hemoglobin status of non-anemic school-age children . Subjects and methods 73 Bolivian non-anemic school-age children r and omly assigned to the treatment group ( n=37 ; receiving supplements containing FeSO4 during 18 weeks ) or the control group ( n=36 ; receiving a placebo during the same period ) . Hemoglobin concentration and anthropometric measures were determined for each child at the beginning ( T0 ) and the end ( T18 ) of the study . Results The treatment group did not show any significant variation in hemoglobin concentration between T0 and T18 ( −1.6±10.4 g/L ; P=0.40 ) whereas the control group showed a significant decrease in hemoglobin concentration ( −4.6±10.9 g/L ; P=0.03 ) . Anthropometric changes were not significantly different between the treatment and the control groups for weight , ( 1.63±1,11 kg vs 1.88±0.79 kg ; P=0.30 ) , height ( 2.35±0.94 cm vs 2.11±1.03 cm ; P=0.34 ) or mid-upper arm circumference ( 0.29±0.57 cm vs 0.22±0.54 cm ; P=0.64 ) . Conclusion In our study , weekly iron supplementation of non-anemic school-age children had no negative effect on their growth while having a positive effect in preventing significant decreases in hemoglobin concentration . These results suggest that in regions where iron deficiency anemia ( IDA ) is prevalent , a simple and cost-effective way to control IDA in school-age children is to give weekly iron supplements to all children at school The incidence of infections was studied in 137 iron-deficient Somali nomads , 67 of whom were treated with placebo and 71 with iron . Seven episodes of infection occurred in the placebo group and 36 in the group treated with iron ; these 36 episodes included activation of pre-existing malaria , brucellosis , and tuberculosis . This difference suggested that host defence against these infections was better during iron deficiency than during iron repletion . Iron deficiency among Somali nomads may be part of an ecological compromise , permitting optimum co-survival of host and infecting agent Background / Objectives : Iron deficiency anemia is a major public health problem in developing countries and may affect school performance and physical work capacity in nonpregnant adolescents , and may increase the risk of anemia during subsequent teenage pregnancies . We assessed the effect of weekly iron ( 120 mg elemental iron ) and vitamin A ( 25 000 IU ) supplementation on hemoglobin , iron status and malaria and nonmalaria morbidity in adolescent schoolgirls . Subjects/ Methods : A total of 279 schoolgirls aged 12–18 years from public primary schools in Kisumu , western Kenya . Double-blind r and omized placebo-controlled trial using a factorial design . Results : Five months of iron supplementation was associated with a 0.52 g dl−1 ( 0.21 , 0.82 ) greater increase in hemoglobin relative to iron placebo . The effect was only observed in girls with iron deficiency on enrollment ( 1.34 g dl−1 ( 0.79 , 1.88 ) ) , but not in iron-replete girls ( −0.20 g dl−1 ( −0.59 , 0.18 ) ) . Similar differences in treatment effect were seen between menstruating and nonmenstruating girls . The effect of iron was independent of vitamin A. The baseline prevalence of vitamin A deficiency was low ( 6.7 % ) and no sustained increase in hemoglobin was seen with weekly vitamin A ( −0.07 g dl−1 ( −0.38 , 0.25 ) ) . Incidence of malaria parasitemia was higher in the iron than iron-placebo groups ( Rate ratio 1.33 ( 0.94 , 1.88 ) ) . Conclusions : Weekly iron supplementation results in substantial increases in hemoglobin concentration in adolescent schoolgirls in western Kenya , which may outweigh possible risks caused by malaria , but only in iron-deficient or menstruating girls and not in iron-replete and nonmenstruating girls BACKGROUND Malaria and anaemia , especially that due to iron deficiency , are two leading causes of morbidity worldwide . Little is known about the relative contribution of Plasmodium falciparum infection and iron deficiency to the aetiology of anaemia in malaria-endemic areas . We undertook a r and omised comparison of different strategies for control of anaemia and malaria in infants , including an assessment of the effect of iron supplementation on malaria susceptibility . METHODS 832 infants born at one hospital in a malaria-hyperendemic area of Tanzania between January and October , 1995 , were r and omly assigned to group DI , receiving daily oral iron ( 2 mg/kg daily ) plus weekly Deltaprim ( 3.125 mg pyrimethamine plus 25 mg dapsone ) ; group IP , receiving iron plus weekly placebo ; group DP , receiving daily placebo plus weekly Deltaprim ; or group PP . supplementation was given from 8 to 24 weeks of age , and the weekly chemoprophylaxis from 8 to 48 weeks . The frequency of severe anaemia ( packed-cell volume < 25 % ) and malaria episodes was assessed through a combination of passive case detection and cross-sectional surveys . FINDINGS The groups that received iron supplementation had a lower frequency of severe anaemia than those that did not receive iron ( 0.62 vs 0.87 cases per person-year ; protective efficacy 28.8 % [ 95 % CI 6.3 - 45.8 ) . Iron supplementation had no effect on the frequency of malaria ( 0.87 vs 1.00 cases per person-year ; protective efficacy 12.8 % [ -12.8 to 32.5 ] ) . The groups that received malaria prophylaxis had lower frequencies of both severe anaemia ( 0.45 vs 1.04 episodes per person-year ; protective efficacy 57.3 % [ 43.0 - 67.9 ] ) and malaria ( 0.53 vs 1.34 episodes per person-year ; protective efficacy 60.5 % [ 48.2 - 69.9 ] ) than the groups that did not receive prophylaxis . After the end of the intervention period , children who had received malaria chemoprophylaxis had higher rates of severe anaemia and malaria than non-chemoprophylaxis groups ( relative risks 2.2 [ 1.3 - 3.7 ] and 1.8 [ 1.3 - 2.6 ] ) . INTERPRETATION Malaria chemoprophylaxis during the first year of life was effective in prevention of malaria and anaemia but apparently impaired the development of natural immunity . Iron supplementation was effective in preventing severe anaemia without increasing susceptibility to malaria . Our findings support iron supplementation of infants to prevent iron-deficiency anaemia , even in malaria-endemic areas In a coastal population in whom anaemia was common , two r and omised controlled trials were undertaken to investigate the effectiveness of treating iron deficiency anaemia at a dispensary and at primary schools . For anaemic adult villagers treated at a dispensary , one dose of tetrachlorethylene for hookworm infection and a once per week visit to collect medicines were found to be satisfactory . A small but significant increase in haemoglobin level was produced by four weeks oral iron therapy , but this was only maintained after seven months by the group that had initially also received tetrachlorethylene . In children ( 5 - 14 years ) no significant rise in haemoglobin level was obtained by using oral iron and /or TCE , either at the dispensary or at the primary schools . This suggests that malaria was a more potent cause of anaemia in these children In Vietnam the high prevalence of iron deficiency anaemia in infants and young children speaks for implementing early interventions . This study aim ed to evaluate the efficacy of the daily iron supplementation in infants given by their mothers and of the weekly iron supplementation . Two hundred and seventy infants aged 5 to 12 months , were divided into four groups . Group 1 received a placebo daily and group 2 a daily dose of 15 mg iron ( 2.0 + /- 0.3 mg iron/day/kg body weight ) which was given by their mothers for three months . Group 3 received a daily dose of 15 mg iron and group 4 a weekly dose of 15 mg iron given during 6 months by health auxiliaries . The hemoglobin concentration ( Hb ) was measured before the intervention and after 3 months of supplementation in all groups , and again after 6 months of supplementation in groups 3 and 4 . After 3 months of iron supplementation , the hemoglobin concentration increased significantly by 21.6 + /- 12.3 g/l and the prevalence of anaemia decreased from 81.3 % to less than 9 % in group 2 . The weekly iron supplementation was significantly less effective than the daily supplementation : after 3 months , Hb increased by 15.4 + /- 13.3 g/l in group 3 and by 11.2 + /- 10.2 g/l in group 4 ( p = 0.04 ) and the prevalence of anaemia was 17.9 % and 41.5 % in groups 3 and 4 , respectively . After 6 months of supplementation , changes in Hb were not significantly different between group 3 ( 22.0 + /- 12.1 g/l ) and group 4 ( 20.0 + /- 10.0 g/l , p = 0.30 ) . However , the final hemoglobin concentration was significantly lower in group 4 ( 120.5 + /- 7.2 g/l ) than in group 3 ( 123.6 + /- 7.8 , p = 0.02 ) . Moreover , nearly 8 % of the children were still anemic in group 4 versus 0 % in group 3 . Since the early developmental period , when the brain and other specific organs are especially sensitive to iron deficiency , is critical , 3-month daily iron supplementation of infants from the age of 6 months has to be recommended , followed by a weekly iron supplementation until the age of 15 months . The community approach , where mothers informed on the importance of iron deficiency anaemia and on the consequences for the health of their infants gave the iron supplements , was shown to be effective . However , its sustainability would depend on the availability of low-cost iron supplements affordable by population s with limited economic re sources . Other interventions , such as iron supplementation of women during fertile age , especially during pregnancy and lactation periods , and the use of complementary food to breast milk , fortified with micronutrients , should be associated Objective : To evaluate the effect of combined iron – zinc supplementation on micronutrient status , growth and morbidity . Design : R and omized , double-masked , placebo-controlled supplementation trial . Setting : Rural district of Que Vo , in the Red River Delta in Vietnam . Subjects : A total of 915 breast-fed infants aged 4–7 months were included and 784 completed the study . Interventions : The Fe-group received daily and for a 6-month period 10 mg of iron , the Zn-group 10 mg zinc , the Fe – Zn group 10 mg iron+10 mg zinc and the placebo group a placebo . Hemoglobin ( Hb ) , serum ferritin ( SF ) and zinc ( SZn ) , and anthropometry were measured before and at the end of the intervention . Morbidity was recorded daily . Results : Changes of Hb and SF were higher in both Fe and Fe+Zn groups ( respectively 22.6 and 20.6 g/l for Hb ; 36.0 and 24.8 μg/l for SF ) compared to Zn and placebo groups ( Hb : 6.4 and 9.8 g/l ; SF : −18.2 and −16.9 μg/l , P<0.0001 ) . SZn increased more in Zn group ( 10.3 μmol/l ) than in Fe+Zn group ( 8.0 μmol/l , P=0.03 ) and more in these groups compared to Fe and placebo groups ( 1.6 and 1.2 μmol/l , P<0.0001 ) . Weight gain was higher in the Zn group . No significant effects of supplementations on growth in length or morbidity . Conclusions : Combined iron – zinc supplementation had a positive effect on iron and zinc status in infants . However , the positive effect of zinc alone on SZn and weight would indicate a negative interaction of iron when added to zinc supplements . Sponsorship : UNICEF New York We used a prospect i ve , open-label r and omized trial to evaluate two treatment regimens in Tanzanian children two months to four years of age presenting to a hospital with a packed cell volume ( PCV ) < 25 % . Treatment was either st and ard ( 14 days of ferrous sulfate and an antimalarial ) or extended ( three months of ferrous sulfate and three antimalarial treatments ) . The prevalence of anemia was measured two weeks after completion of treatment and six months after recruitment . Two weeks after completing treatment , the prevalence of PCV < 33 % was 58 % in the st and ard treatment arm and 44 % in the extended treatment group ( P = 0.04 ) , and the mean PCV was significantly higher in the extended treatment arm ( 32.1 % , SD = 4.5 % versus 30.8 % , SD = 4.9 % ; P = 0.031 ) . However , there was no difference in the prevalence of PCV < 25 % in the first survey , and the benefits of extended therapy were only apparent six months after recruitment in children compliant with the extended treatment ( odds ratio of PCV < 25 % = 0.16 , P = 0.06 ) . Compliance was satisfactory in only 39 % ( 82 of 209 ) of the children in the first week of treatment . Extending the duration of therapy and improving compliance may have health benefits for anemic children in malaria-endemic setting A placebo-controlled trial of intramuscular iron dextran prophylaxis for two-month-old infants was carried out on the north coast of Papua New Guinea where there is high transmission of malaria . The results indicate that the placebo group became relatively iron deficient whereas the iron dextran group had adequate iron stores and , in the absence of malaria , a higher mean haemoglobin . However in the iron dextran group there was a higher prevalence of malaria , as judged by parasite and spleen rates at 6- and 12-month follow-up ; a lower haemoglobin associated with malaria when compared with the placebo group and a greater reticulocytosis in response to malaria infection . Within the placebo group it was noticed that the malaria rates were lower at follow-up in those infants who had had a low birth haemoglobin . In neither group was there apparent suppression of marrow activity in the presence of malaria . Malaria infection in both groups was associated with a significantly raised serum ferritin level and transferrin saturation . Over-all these data give evidence for a protective role of iron deficiency against malaria and would argue against the injudicious use of iron replacement in areas where malaria is endemic OBJECTIVE To examine the benefits of anemia prophylaxis in adolescent school.girls by weekly or daily iron-folate supplementation . DESIGN Prospect i ve study . SETTING Government girl schools of northeast Delhi . SUBJECTS 2088 subjects ( with hemoglobin greater than 7.9 g/dL ) , including 702 on daily and 695 on weekly iron-folate administration ; 691 girls served as controls . RESULTS About 85 % girls were iron deficient out of which 49.3 % were anemic . Weekly administration took longer time to raise hemoglobin but was effective as well as practical . Plasma ferritin estimation in girls showed rise in level in both the treated groups . CONCLUSION Weekly administration of iron-folate was a practical and effective strategy for anemia prophylaxis in adolescent school girls Background . The observation of an increased prevalence of allergic disorders coinciding with a decreasing frequency of infectious diseases in early childhood has led to the speculation that infections may prevent allergic sensitization . Information on the role of parasites in this context is limited . Bronchiolitis in infancy has been linked with asthmatic symptoms later in childhood , although the underlying cause of this association is unknown . Methods . To test the hypothesis that early parasitic infections in infancy might prevent the development of allergic manifestations later in life , the effect of malaria infections during the first year of life on the risk of bronchiolitis was studied in 675 Tanzanian children at 18 months of age . The study was conducted as part of an intervention trial of malaria chemoprophylaxis and /or iron supplementation for the prevention of malaria and anemia in infants . Results . The incidence of bronchiolitis up to 18 months of age in the 675 children was 0.58 episode per child per year . The risk factors analysis was based on 470 children with complete data . There was no difference in the incidence of bronchiolitis between those who had received malaria chemoprophylaxis during the first year of life and those who had not . However , the proportion of children who had bronchiolitis was lower among those who had had malaria episodes than among those who had not ( 48%vs . 55 % , P = 0.05 ) . Conclusions . This study does not support the hypothesis that reduced exposure to parasites may modulate the development of bronchiolitis early in life Objective : To determine the effectiveness of combined iron and zinc over the iron or zinc-only supplementation in correcting deficiency and possible interactive effects in a group of adolescent school children . Subjects and methods : Schoolchildren ( n=821 ) of 12–16 years of age were r and omized into four groups and supplemented with iron ( 50 mg/day ) , zinc ( 14 mg/day ) , iron+zinc or placebo capsules 5 days per week for 24 weeks . Anthropometry , and haemoglobin ( Hb ) , serum zinc ( SZn ) and serum ferritin ( SF ) concentrations were determined before and after the intervention . Results : There were no significant effects between-groups in their weight , height and Hb concentrations with the intervention when compared with the placebo group . Iron-only and combination-supplemented groups had reached mean SF concentrations of 55.1 μg/l with no difference between them ( P=0.99 ) . The zinc-only group had a mean change of 4.3 μmol//l whereas the combine-supplemented group had a mean change of 4.0 μmol/l ( P=0.82 ) . The prevalence of anaemia was found to be 70.3 % in the iron group at baseline ; this was reduced to 14.5 % after the supplementation . In the combine-supplemented group anaemia , prevalence was reduced from 64.8 to 19.3 % . Conclusions : Zinc alone or in combination with iron has not shown a significant improvement in growth in adolescence . Severe and moderate forms of anaemia were successfully treated in children who received iron supplementation . Initial high prevalence of low SZn and iron stores was significantly improved with micronutrient supplementation The control of childhood anaemia in malaria holoendemic areas is a major public health challenge for which an optimal strategy remains to be determined . Malaria prevention may compromise the development of partial immunity . Regular micronutrient supplementation has been suggested as an alternative but its effectiveness remains unsettled . We therefore conducted a r and omised placebo-controlled intervention trial with 207 Tanzanian children aged 5 months to 3 years on the efficacy of supervised supplementation of low-dose micronutrients including iron ( Poly Vi-Sol with iron ) three times per week , with an average attendance of > /= 90 % . The mean haemoglobin ( Hb ) level increased by 8 g/l more in children on supplement ( 95 % CI 3 - 12 ) during the 5-month study . All age groups benefited from the intervention including severely anaemic subjects . The mean erythrocyte cell volume ( MCV ) increased but Hb in children > /= 24 months improved independently of MCV and no relation was found with hookworm infection . The data therefore suggest that micronutrients other than iron also contributed to Hb improvement . In the supplement group of children who had received sulfadoxine-pyrimethamine ( SP ) treatment , the mean Hb level increased synergistically by 22 g/l ( 95 % CI 13 - 30 ) compared to 7 g/l ( 95 % CI 3 - 10 ) in those without such treatment . Supplementation did not affect malaria incidence . In conclusion , micronutrient supplementation improves childhood anaemia in malaria holoendemic areas and this effect is synergistically enhanced by temporary clearance of parasitaemia Background / Objectives : Despite repeated public commitments and availability of various forms of iron supplements , rates of anaemia in developing countries remain high . A major reason for this lack of success has been poor adherence . The objective of this study was to compare the effectiveness of daily and flexible administration of micronutrient Sprinkles on adherence , acceptability and haematological status among young children in rural Bangladesh . Subjects/ Methods : A sample of 362 children ( haemoglobin (Hb)⩾70 g l−1 ) aged 6–24 months were cluster-r and omized to receive 60 sachets of Sprinkles either ( i ) daily over 2 months ; ( ii ) flexibly over 3 months ; or ( iii ) flexibly over 4 months . With a flexible regimen , mothers/caregivers decided how frequently to use Sprinkles without exceeding one sachet per day . Adherence was assessed monthly by counting the number of sachets used and acceptability was evaluated through focus group discussion s. Haemoglobin was measured at baseline , at the end of each intervention period and 6 months post-intervention . Results : Mean percent adherence was significantly higher in the flexible-4-month group ( 98 % ) compared to the flexible-3-month ( 93 % ) and daily-2-month ( 88 % ) groups ( P<0.01 ) . Most mothers found flexible administration to be more acceptable than daily due to perceived benefits of use . Hb at the end of intervention was significantly higher in the flexible-4-month group compared to the daily group ( P=0.03 ) . Anaemia prevalence decreased by 65 % in the flexible-4-month group compared to 54 % in the flexible-3-month and 51 % in the daily-2-month groups . Percent of cured children who maintained a non-anaemic status 6 months post-intervention was significantly higher in the flexible-4-month ( 82 % ) and flexible-3-month ( 80 % ) groups than the daily-2-month ( 53 % ) group ( P<0.05 ) . Conclusions : The adherence , acceptability and haematological response to flexible administration over 4 months were found preferable to daily INTRODUCTION Iron deficiency is widespread in the developing world and is especially common in young children who live on the Indian subcontinent . Supplementation with iron and folic acid alleviates severe anaemia and enhances neurodevelopment in deficient population s , but little is known about the risks of mortality and morbidity associated with supplementation . METHODS We did a community-based , cluster-r and omised , double-masked , placebo-controlled , 2x2 factorial trial in children aged 1 - 36 months and residing in southern Nepal . We r and omly assigned children daily oral supplementation to age 36 months with : iron ( 12.5 mg ) and folic acid ( 50 microg ; n=8337 ) , zinc alone ( 10 mg ) , iron , folic acid , and zinc ( n=9230 ) , or placebo ( n=8683 ) ; children aged 1 - 11 months received half the dose . Our primary outcome measure was all-cause mortality , and our secondary outcome measures included cause-specific mortality and incidence and severity of diarrhoea , dysentery , and acute respiratory illness . Analyses were by intention to treat . This study is registered at , number NCT00109551 . FINDINGS The iron and folic acid-containing groups of the study were stopped early in November , 2003 , on the recommendation of the data and safety monitoring board ; mortality in these groups did not differ from placebo and there was low power to detect positive or negative effects by the time enrollment was completed . We continued to enroll children to the placebo and zinc alone groups . 25,490 children participated and analyses are based on 29,097.3 person-years of follow-up . There was no difference in mortality between the groups who took iron and folic acid without or with zinc when compared with placebo ( HR 1.03 , 95 % CI 0.78 - 1.37 , and 1.00 , 0.74 - 1.34 , respectively ) . There were no significant differences in the attack rates for diarrhoea , dysentery , or respiratory infections between groups , although all the relative risks except one indicated modest , non-significant protective effects . INTERPRETATION Daily supplementation of young children in southern Nepal with iron and folic acid with or without zinc has no effect on their risk of death , but might protect against diarrhoea , dysentery , and acute respiratory illness OBJECTIVE . Lead exposure in children has been associated with both global and specific cognitive deficits . Although chelation therapy is advised for children with blood lead concentrations of > 44 μg/dL , treatment options for children with lower blood lead values are limited . Because lead absorption is related to children 's nutritional status , micronutrient supplements may be 1 strategy for combating low-level , chronic lead exposure . This study was design ed to test the efficacy of iron and zinc supplementation for lowering blood lead concentrations and improving cognitive performance in schoolchildren who live in a lead-contaminated city . METHODS . This r and omized , double-blind , placebo-controlled field trial was conducted in public elementary schools in Torreón , an industrialized city in northern Mexico . A metal foundry , located close to the city center and within 3.5 km of 9 schools , was the main source of lead exposure . A total of 602 children who were aged 6 to 8 years and regularly attending first grade in the study schools were enrolled . Children were given 30 mg of iron , 30 mg of zinc , both , or a placebo daily for 6 months . A total of 527 completed the treatment , and 515 were available for long-term follow-up , after another 6 months without supplementation . Eleven cognitive tests of memory , attention , visual-spatial abilities , and learning were administered at baseline and each follow-up . RESULTS . There were no consistent or lasting differences in cognitive performance among treatment groups . CONCLUSIONS . Daily supplementation with iron and /or zinc may be of limited usefulness for improving cognition in lead-exposed schoolchildren . However , these treatments may be effective in setting s with higher prevalence of nutritional deficiencies or in younger children BACKGROUND Malaria is a major cause of infant morbidity and mortality in sub-Saharan Africa , and is often complicated by severe anaemia . Resistance of Plasmodium falciparum to most affordable antimalarial drugs is an impediment to intermittent chemotherapy . We investigated the effect of presumptive intermittent treatment with amodiaquine and daily iron supplementation in infants on malarial fevers and anaemia , in a holoendemic area of Tanzania where malaria is largely resistant to chloroquine and sulfadoxine/ pyrimethamine . METHODS 291 infants aged 12 - 16 weeks who attended three clinics were r and omised to receive amodiaquine , iron supplementation , amodiaquine plus iron supplementation , or placebo . Over 6 months , we gave amodiaquine three times with intervals of 60 days ; oral iron supplementation was given daily . Malarial fevers and anaemia were monitored at bimonthly treatment visits and by self-reporting to health centres . FINDINGS The protective efficacy of intermittent amodiaquine treatment in prevention of malarial fevers and anaemia was 64.7 % ( 95 % CI , 42.4 - 77.2 ) and 67.0 % ( 95 % CI , 34.5 - 83.4 ) , respectively . Protective efficacy was similar in the group receiving amodiaquine plus iron supplementation . Infants receiving iron supplementation only were partly protected against anaemia ( protective efficacy 59.8 % ; 95 % CI , 23.4 - 78.9 ) , but not against malarial fevers . 4 months ' follow-up did not show rebound morbidity . We noted no haematological or clinical adverse effects . INTERPRETATION Presumptive intermittent treatment for malaria with amodiaquine reduced malarial fevers and anaemia in infants , in an area with high resistance to other antimalarials . Intermittent treatment strategies for malaria in highly endemic areas could be of great benefit to public health In a double-blind , placebo-control prospect i ve cohort study of 196 infants from birth to 15 months of age , assessment was made at 12 months of age of the relationship between iron status and psychomotor development , the effect of a short-term ( 10-day ) trial of oral iron vs placebo , and the effect of long-term ( 3 months ) oral iron therapy . Development was assessed with the mental and psychomotor indices and the infant behavior record of the Bayley Scales of Infant Development in 39 anemic , 30 control , and 127 nonanemic iron-deficient children . Anemic infants had significantly lower Mental and Psychomotor Developmental Index scores than control infants or nonanemic iron-deficient infants ( one-way analysis of variance , P less than .0001 ) . Control infants and nonanemic iron-deficient infants performed comparably . No difference was noted between the effect of oral administration of iron or placebo after 10 days or after 3 months of iron therapy . Among anemic infants a hemoglobin concentration less than 10.5 g/dL and duration of anemia of greater than 3 months were correlated with significantly lower motor and mental scores ( P less than .05 ) . Anemic infants failed specifically in language capabilities and body balance-coordination skills when compared with controls . These results , in a design in which intervening variables were closely controlled , suggest that when iron deficiency progresses to anemia , but not before , adverse influences in the performance of developmental tests appear and persist for at least 3 months despite correction of anemia with iron therapy . If these impairments prove to be long st and ing , prevention of iron deficiency anemia in early infancy becomes the only way to avoid them BACKGROUND In developing countries there is high prevalence of iron deficiency anemia , which causes negative impact on growth , development and quality of life for infant population . Currently several strategies are being elaborated and tested to tackle this problem . OBJECTIVE To measure anemia prevalence in preschool children . To evaluate fortification effectiveness with 5 or 10 mg of elemental iron/daily added to school meals by increasing hemoglobin levels in anemic children . METHODS Double-blind , cluster r and omized intervention study with 728 students from public network . Blood count was taken at beginning of study , to evaluate anemia prevalence , those anemic were selected for intervention , after intervention new blood count was taken to evaluate fortification effectiveness . Ferrous Sulphate was added in individual dosage of 5 or 10 mg of elemental iron/daily to usual school meal . From 35 schools 3 were r and omized to receive 5 mg/daily ( group A ) and 3 to receive 10 mg/daily ( group B ) . Hemoglobin and hematocrit averages before and after intervention were compared in each group and between them . RESULTS In group A , the anemia prevalence reduced 34.9 to 12.4 % , and in group B 39.0 to 18.7 % . In both groups a significant increase in hemoglobin was observed : in group A from 10.1 to 11.5 g/dl ( p < 0.01 ) and in group B from 10.0 to 11.0 g/dl ( p < 0.01 ) . There was no statistically significant difference in final levels of hemoglobin among groups . CONCLUSIONS Both dosages of elemental iron were equally effective in increasing hemoglobin levels , and reducing anemia prevalence . Fortification of school meals was shown to be an effective , low cost and easy to manage intervention BACKGROUND Iron is essential for the growth and virulence of many pathogenic enterobacteria , whereas beneficial barrier bacteria , such as lactobacilli , do not require iron . Thus , increasing colonic iron could select gut microbiota for humans that are unfavorable to the host . OBJECTIVE The objective was to determine the effect of iron fortification on gut microbiota and gut inflammation in African children . DESIGN In a 6-mo , r and omized , double-blind , controlled trial , 6 - 14-y-old Ivorian children ( n = 139 ) received iron-fortified biscuits , which contained 20 mg Fe/d , 4 times/wk as electrolytic iron or nonfortifoed biscuits . We measured changes in hemoglobin concentrations , inflammation , iron status , helminths , diarrhea , fecal calprotectin concentrations , and microbiota diversity and composition ( n = 60 ) and the prevalence of selected enteropathogens . RESULTS At baseline , there were greater numbers of fecal enterobacteria than of lactobacilli and bifidobacteria ( P < 0.02 ) . Iron fortification was ineffective ; there were no differences in iron status , anemia , or hookworm prevalence at 6 mo . The fecal microbiota was modified by iron fortification as shown by a significant increase in profile dissimilarity ( P < 0.0001 ) in the iron group as compared with the control group . There was a significant increase in the number of enterobacteria ( P < 0.005 ) and a decrease in lactobacilli ( P < 0.0001 ) in the iron group after 6 mo . In the iron group , there was an increase in the mean fecal calprotectin concentration ( P < 0.01 ) , which is a marker of gut inflammation , that correlated with the increase in fecal enterobacteria ( P < 0.05 ) . CONCLUSIONS Anemic African children carry an unfavorable ratio of fecal enterobacteria to bifidobacteria and lactobacilli , which is increased by iron fortification . Thus , iron fortification in this population produces a potentially more pathogenic gut microbiota profile , and this profile is associated with increased gut inflammation . This trial was registered at controlled-trials.com as IS RCT N21782274 In order to increase the intestinal absorption of iron whilst simultaneously minimising the side-effects and thus increasing compliance , once- or twice-weekly , instead of daily , iron supplementation has been widely recommended . In a r and omized , placebo-controlled , double-blind study in western Kenya , a tablet of ferrous dextran ( containing 60 mg elemental iron ) or an identical-looking placebo tablet was provided twice-weekly for 12 months to each child or adult investigated . At baseline each subject had a moderately low blood concentration of haemoglobin ( Hb ) . Initial Hb and serum ferritin ( SF ) concentrations were determined and each subject was tested for malarial and helminth infection and treated , if necessary , with the appropriate anthelminthic drug(s ) . Overall , 200 children ( aged 4 - 15 years ) and 129 adults ( aged 16 - 63 years ) completed the 12-month study . At baseline , 47.5 % of the children and 58.1 % of the adults were anaemic , hookworm ( detected in 60.0 % of the children and 69.9 % of the adults ) was the most common helminth infection , and malaria was endemic . The results of bivariate analyses indicated that twice-weekly iron supplementation had no significant effect on blood Hb or SF concentrations , either in the children or the adults investigated . The results were confirmed in multiple linear-regression analyses , which revealed that the predictors of the final Hb concentration in the children investigated were age and infection , after enrollment , with Ascaris lumbricoides . Gender and the serum concentration of alpha-1-antichymotrypsin ( ACT ) at final follow-up were predictors of the final SF concentration in the children . In adults , the predictors of the final Hb concentration were gender and HIV infection , and the predictors of the final SF concentration were age and the serum concentration of ACT at the final follow-up . Twice-weekly iron supplementation did not increase Hb or iron stores in children or adults . Since compliance appeared to be high , this lack of effect may be the result of an inadequate dose of iron or of subjects who have deficiencies in micronutrients other than iron To combat iron deficiency manifesting around six months of age , iron-fortified complementary feeding has been recommended . In developing countries , in view of the poor bioavailability of iron from predominantly cereal-based diets and the high cost of fortification , medicinal iron supplementation is an alternative intervention . This double-blind r and omized placebo-controlled trial was conducted from April 1999 to March 2000 in the Out-patient Department of a tertiary hospital in New Delhi , India , to evaluate the haematological effects of medicinal iron supplementation to breastfed young infants initiated on complementary feeding . One hundred healthy non-low birth-weight , predominantly breastfed infants aged 4 - 6 months were r and omized into two groups to receive either iron ( 2 mg/kg/day ) ( IS group ; n=49 ) or placebo drops ( P group ; n=51 ) beginning with the initiation of home-based non-fortified complementary feeding . Haematological parameters and anthropometry of mothers and infants were measured at baseline and repeated for infants after four and eight weeks of recruitment . Seventy-one subjects ( 35 in the IS group and the 36 in P group ) came for the first follow-up , and of these , 43 ( 19 in the IS group and 24 in the P group ) reported for the second visit . The adjusted ( for maternal and baseline infant ferritin ) serum ferritin levels were significantly higher in the IS group at both the follow-ups ( p=0.006 ) . The adjusted ( for maternal ferritin and baseline infant ferritin ) change in haemoglobin was significantly higher only at the second follow-up ( 0.7 g/dL ; 95 % confidence interval [ CI ] 0.3 - 1.0 g/dL ) . The adjusted rise in haemoglobin was higher in initially anaemic infants ( at second follow-up by 1 g/dL ; 95 % CI 0.5 - 1.6 g/dL ) . Medicinal iron supplementation , at the time of initiating complementary feeding , to breastfed young infants result ed in an elevation of serum ferritin and haemoglobin . The response was higher in initially anaemic infants . From a programmatic perspective , evidence needs to be generated on the relative merits of selective ( anaemic ) versus general supplementation and daily versus weekly supplementation Objective : High prevalences of vitamin A deficiency and anaemia among adolescents warrant interventions . This study evaluated the effectiveness of school-based supplementation to reduce anaemia and improve vitamin A status . Design : School-based , grade -r and omized , intervention . Subjects and setting : In all , 1757 girls and 1859 boys , aged 12–15 y , in 24 Junior High Schools . Interventions : Weekly supplementation for 14 weeks with 60 mg iron and 250 μg folate ( Fe group ; n=978 ) , 10 000 IU vitamin A ( VA group ; n=970 ) or both ( VAFe group ; n=1042 ) to subjects in 15 schools , compared to subjects in nine other schools not receiving supplements ( control ; n=626 ) . Results : The baseline anaemia prevalence ( Hb < 120 g/l ) in girls was 20 % ( prepubertal ) and 26 % ( pubertal ) , and in boys 24 % ( pre-pubertal ) and 11 % ( pubertal ) . Serum retinol concentrations were low ( < 1.05 μmol/l ) in 41 % of boys and 45 % of girls . The interventions did not increase haemoglobin concentrations . Serum retinol concentration of boys , but not girls , in the VA group increased ( 0.33 vs 0.07 μmol/l in controls ; P<0.01 ) . The risk factors for low serum retinol concentration were lower baseline serum retinol concentration ( OR 0.02–0.03 ) with , for girls , nightblindness at baseline ( OR 5.88 ) , and for boys , not receiving vitamin A ( OR control : 1.00 ; VA : 0.37 ; Fe : 0.77 ; VAFe : 0.34 ) and maternal illiteracy ( OR mother never attended school 1.00 , mother received any formal education 0.17–0.33 ) . Conclusions : Supplementation with vitamin A increased serum retinol concentration of boys . Iron supplementation did not change Hb . This appeared to be due to poor compliance , and partly related to side effects . Sponsorship : This study was funded by USAID through the OMNI Project Objective : To assess the impact of a daily oral iron supplementation on hematological status , cell-mediated immunity and susceptibility to infections in children living in an environment where iron deficiency , malaria and other infections are frequent . Design : R and omized , double-blind iron supplementation including a placebo group . Setting : A village in Togo , West Africa . Subjects : Of the 229 6–36-month-old children of both sexes recruited , 197 with hemoglobin concentration ≥80 g/l were included and 163 completed the study .Intervention : Children received daily a placebo ( n=79 ) or a dose of 2–3 mg of elemental iron per kg of body weight ( n=84 ) for 3 months . Hematological , nutritional and immune status were assessed at the beginning and at the end of the supplementation period , and 6 months later . Morbidity was recorded throughout the study . Results : Iron supplementation had a significant and positive effect on iron status of children and no impact on the incidence of infections , especially malaria . Its probable effect on immune status was masked by interference of infections and their treatment , which contributed to improve hematological and immune status in both groups . Conclusion : According to the negative consequences of anemia and iron deficiency on global child development , control of iron deficiency by oral iron supplementation in young children has to be conducted , associated with prophylaxis and treatment of malaria and repeated deworming . Sponsorship : Program supported by IRD.European Journal of Clinical Nutrition ( 2000 ) 54 , OBJECTIVE We evaluated the effect of a micronutrient-fortified beverage on growth and morbidity in apparently healthy schoolchildren . METHODS This was a double-blind , placebo-controlled , matched-pair , cluster , r and omized study in semi-urban middle-income residential schoolchildren aged 6 to 16 y. Anthropometrics ( height and weight ) , clinical symptoms of deficiency , and morbidity data were collected at baseline in the supplemented group ( n = 446 in 10 grade s ) and the placebo group ( n = 423 in 10 grade s ) and after 14 mo of supplementation ( n = 355 in the supplement group and n = 340 in the placebo group from nine pairs ) . RESULTS After 14 mo of supplementation , there was a significant increase in mean increments of height and weight z scores of -0.04 and 0.02 , respectively , in the supplemented group compared with -0.14 and -0.09 in the placebo group . Velocity of weight ( 3.56 versus 3.00 ) was significantly ( P < 0.01 ) higher with supplementation . Although there were no differences in the incidence of common childhood diseases such as fever , cough and cold , diarrhea , and ear infections elicited for a reference period of 1 mo at every quarterly follow-up examination , the mean duration of illness ( calculated per person per year ) was significantly shorter ( 5.0 d ) in the supplemented group than in the placebo group ( 7.4 d ) . CONCLUSIONS The micronutrient-fortified beverage was beneficial in promoting growth and decreasing duration of common illnesses among middle-class residential schoolchildren who had adequate energy and protein intakes Iron-deficient anaemic infants perform worse in tests of mental and motor development than do iron-sufficient infants of a comparable age . A r and omised , double-blind trial was done to monitor the effects of iron supplementation on performance in the Bayley scales of mental and motor development among 12 - 18-month-old infants in Indonesia . Iron-deficient anaemic infants ( n = 50 ) were assigned r and omly to receive dietary ferrous sulphate or placebo for 4 month . Similar treatment r and omisation was done among nonanaemic iron-deficient ( n = 29 ) and iron-sufficient ( n = 47 ) infants . Before intervention , the mean mental and motor scores of the iron-deficient anaemic infants were significantly ( p < 0.01 ) lower than those of the nonanaemic iron-deficient and iron-sufficient classes . After intervention , developmental delays were reversed among iron-deficient anaemic infants who had received iron but they remained the same among placebo-treated iron-deficient anaemic infants . Neither ferrous sulphate nor placebo had significant effects on the scores of the other two iron-status classes . The poor performance of 12 - 18-month-old iron-deficient anaemic infants in the Bayley scales of mental and motor development can be improved to the level of performance of iron-sufficient infants by treatment with ferrous sulphate Previous data from Vietnam show that anaemia is highly prevalent among schoolchildren , who are considered not to be iron deficient . Trichuris infection doubled the risk of anaemia . The present study aim ed to evaluate the hypothesis that de-worming is more effective than iron fortification in an anaemic , infection-prone population . In a trial with a 2 x 2 factorial design , 425 anaemic children aged 6 - 8 years were r and omly assigned to receive either iron-fortified noodles or placebo , and mebendazole or placebo . Outcomes considered were change in haematological indicators of iron status ( Hb , serum ferritin ( SF ) , serum transferrin receptor ( TfR ) and haemoglobinopathies analysis ) ; inflammations ( C-reactive protein ( CRP ) ) ; parasite infection status ( hookworm , Trichuris and Ascaris infection ) ; and IgE. ANOVA and logistic regression were used to assess the effects of iron fortification and de-worming on Hb , SF , TfR , body iron and anaemia . Hb improved in all groups after 6 months of intervention . Iron fortification significantly improved Hb , SF and body iron ( 2.6 g/l , 16.3 microg/l and 1 mg/kg , respectively ) . Prevalence of elevated IgE was very high at baseline ( 99 % ) and significantly reduced to about 75 % in all groups after intervention . De-worming unexpectedly showed no effect on Hb , iron status and IgE level . It is concluded that iron fortification slightly improved anaemia and iron status in anaemic schoolchildren in rural Vietnam that were not considered iron deficient . Chronic infection or other unidentified factors may play an important role in the seasonal reduction of anaemia seen in all treatment groups Haematological and iron parameters , measured in 907 children aged from 6 months to 5 years in rural Gambia at the start of the rainy season , differed from those in American reference population s as follows : mean haemoglobin levels were much lower at ages 1 and 2 years and mean levels of mean corpuscular volume ( MCV ) were lower at all ages ( at age 1 year mean haemoglobin was 11.2 g/dl and mean MCV 68.2 fl ) ; in a sample of 249 children r and omly selected from the whole study population , mean serum iron levels were similar but mean transferrin saturation and mean serum ferritin levels were lower , especially at ages 1 - 3 years ( at age 1 year mean serum iron was 11.1 mumol/l , mean transferrin saturation 16.9 % , and geometric mean serum ferritin 8.8 ng/ml . A total of 213 children ( 23 % ) whose haemoglobin and mean corpuscular volume were both less than the 3rd percentile of the reference population received oral iron or placebo from their mothers during the rainy season when malaria transmission is maximal . Mean levels of haemoglobin , mean corpuscular volume , serum iron , transferrin saturation and serum ferritin rose in the iron-treated group and fell in the placebo group at all ages , except under 1 year for serum ferritin , to produce significant differences between the groups by the end of the study . Total iron-binding capacity showed no significant changes during the study . We concluded that oral iron given by the mother during the rainy season can be used to treat iron-deficiency anaemia in Gambian children who would otherwise become more anaemic BACKGROUND Anaemia caused by iron deficiency is common in children younger than age 5 years in eastern Africa . However , there is concern that universal supplementation of children with iron and folic acid in areas of high malaria transmission might be harmful . METHODS We did a r and omised , placebo-controlled trial , of children aged 1 - 35 months and living in Pemba , Zanzibar . We assigned children to daily oral supplementation with : iron ( 12.5 mg ) and folic acid ( 50 mug ; n=7950 ) , iron , folic acid , and zinc ( n=8120 ) , or placebo ( n=8006 ) ; children aged 1 - 11 months received half the dose . Our primary endpoints were all-cause mortality and admission to hospital . Analyses were by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N59549825 . FINDINGS The iron and folic acid-containing groups of the trial were stopped early on Aug 19 , 2003 , on the recommendation of the data and safety monitoring board . To this date , 24 076 children contributed a follow-up of 25,524 child-years . Those who received iron and folic acid with or without zinc were 12 % ( 95 % CI 2 - 23 , p=0.02 ) more likely to die or need treatment in hospital for an adverse event and 11 % ( 1 - 23 % , p=0.03 ) more likely to be admitted to hospital ; there were also 15 % ( -7 to 41 , p=0.19 ) more deaths in these groups . INTERPRETATION Routine supplementation with iron and folic acid in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death . In the presence of an active programme to detect and treat malaria and other infections , iron-deficient and anaemic children can benefit from supplementation . However , supplementation of those who are not iron deficient might be harmful . As such , current guidelines for universal supplementation with iron and folic acid should be revised BACKGROUND Most developing countries have adopted a st and ard WHO dosing schedule for vitamin A supplementation . However , in 2002 the International Vitamin A Consultative Group ( IVACG ) Annecy Accord recommended a new high-dose regimen for mothers and infants . Our aim was to test whether the new high-dose regimen of vitamin A supplementation would increase maternal and infant plasma vitamin A , reduce infant Helicobacter pylori infection and nasopharyngeal pneumococcal carriage , and improve infant gut epithelial integrity . METHODS In an area of moderate vitamin A deficiency in rural Gambia , 220 mother-infant pairs were enrolled in a r and omised double-blind trial between September , 2001 , and October , 2004 , that compared the IVACG high dose with the WHO dose . The primary endpoints were levels of maternal and infant plasma vitamin A , H pylori infection , pneumococcal carriage , and gut epithelial integrity . The trial is registered as IS RCT N 98554309 . FINDINGS 197 infants completed follow-up to 12 months ( 99 high dose and 98 WHO dose ) . There were no adverse events at dosing . No differences were found in the primary outcomes for high-dose versus WHO schedule : maternal vitamin A concentration at 2 months + 0.02 micromol/L ( 95 % CI -0.10 to 0.15 ) ; infant vitamin A at 5 months + 0.01 micromol/L ( -0.06 to 0.08 ) ; H pylori infection at 12 months -0.3 % ( -14.7 to 14.2 ) ; maternal pneumococcal carriage at 12 months -2.0 % ( -13.7 to 9.7 ) ; infant pneumococcal carriage at 12 months -4.1 % ( -15.8 to 7.6 ) ; infant gut mucosal damage at 12 months 5.2 % ( -8.7 to 19.2 ) . There were more clinic attendances by the high-dose group in the first 6 months of life ( p=0.018 ) . INTERPRETATION Our results do not lend support to the proposal to increase the existing WHO st and ard dosing schedule for vitamin A in areas of moderate vitamin A deficiency . Caution is urged for future studies because trials have shown possible adverse effects of higher doses of vitamin A , and potential negative interactions with the exp and ed programme on immunisation ( EPI ) vaccines The study was conducted to determine whether provision of oral supplementary iron to primary school children in Kenya would improve their growth . Children in the two lowest grade s who satisfied study criteria were allocated to either an iron-supplementation group ( n = 29 ) or a placebo group ( n = 26 ) . At the baseline before intervention the groups did not differ significantly in age , sex ratio , prevalence and intensity of intestinal helminthic infections , most anthropometric measurements or hemoglobin levels . Although the study lasted for 32 weeks , children only took iron or placebos on school days thus omitting weekends and school holidays . Examination at the end of the study showed that the iron-supplemented children had grown significantly more in terms of weight , weight for height , arm circumference and skinfold thickness compared with the placebo group . Hemoglobin levels had also improved significantly . We conclude that where iron deficiency anemia and undernutrition are prevalent in children , iron supplementation will improve growth and hemoglobin levels To investigate the efficacy of two different iron supplements administered either on a weekly basis or during menstruation , a 16-week community experimental study was carried out among postmenarcheal female adolescent students in Kupang , East Nusa Tenggara , Indonesia . Forty eight students received a placebo tablet weekly , 48 other students got an iron tablet weekly and 41 students took an iron tablet for four consecutive days during their menstruation cycle . All subjects were given deworming tablets before supplementation . Haemoglobin , serum ferritin , height , weight , mid-upper arm circumference and dietary intake were assessed before and after intervention . The supplementation contributed to a significant improvement in the iron status of the intervention groups compared to the placebo group ( P < 0.05 ) . In the menstruation group , the haemoglobin concentrations of the anaemic subjects improved significantly ( P < 0.05 ) while for the non-anaemic subjects , serum ferritin concentrations also increased significantly ( P < 0.05 ) . In the weekly group for anaemic and nonanaemic subjects , there was a significant increase in both haemoglobin and serum ferritin concentrations ( P < 0.05 ) . This study revealed that weekly supplementation of iron tablets continued for 16 weeks contributed a higher improvement to haemoglobin concentration , compared with supplementing iron tablets for four consecutive days during menstruation for four menstrual cycles . This suggests that weekly iron supplementation is preferable INTRODUCTION In undeveloped countries such as Peru there is a high prevalence of ferropenic anemia . In addition , iron deficiency produces cognitive alterations that could be corrected by iron treatment . OBJECTIVE To evaluate the effect of administration of heme iron-fortified cookies on the intellectual status of preschool children . PATIENTS AND METHODS Using the Goodenough-Harris Test ( GHT ) and Wechsler Preschool and Primary Scale of Intelligence ( WPPSI ) we studied the intellectual status of 53 children who received heme iron-fortified cookies for 6 - 8 weeks and 55 controls without fortification , in 2 occasions ( before and after intervention ) . RESULTS We observed a significantly higher improvement in children who received iron respect to controls for GHT score ( p < 0.001 ) , WPPSI score ( p < 0.05 ) , WPPSI attention-concentration subscale ( p < 0.01 ) and WPPSI pure attention subscale ( p < 0.05 ) . CONCLUSION Administration of heme iron-fortified cookies may improve the intellectual performance of low-income preschool children Ninety preselected children , aged between 8 and 14 years , living in two rural West African ( Gambian ) villages , were r and omly divided into three groups , matched for age and sex . One group received a placebo ( lactose ) tablet , one received riboflavin ( 5 mg ) on 5 d every week , which was sufficient to correct an endemic riboflavin deficiency , and one received a multivitamin supplement ( Protovit ; Hoffmann La Roche ) , on 5 d every week , together with FeSO4 ( 200 mg ) once weekly , and the supplements were given for 1 year . Neuromuscular tests , including arm tremor and manipulative skills , were performed on three occasions : once just before the introduction of the supplements ; again 6 weeks after commencing the supplements ; and again 1 year later . Venous blood sample s were collected at the same time as the first two sets of neuromuscular tests . These sample s were used for haematology and nutrient status indices : plasma ferritin , ascorbic acid , cyanocobalamin and pyridoxal phosphate , and erythrocyte tests for folate status , for riboflavin status ( erythrocyte glutathione reductase activation coefficient ) and thiamine status ( erythrocyte transketolase activation coefficient ) . The riboflavin in both supplements achieved a clear-cut response in biochemical status , which was dose-dependent . The pyridoxine , ascorbic acid and Fe components of the multivitamin also affected the associated biochemical indices . Although overall the arm tremor and related neuromuscular function tests did not respond significantly to the supplements , significant improvement was seen in the boys for the arm-tremor test in both the supplemented groups OBJECTIVE To compare the effectiveness of weekly vs daily iron and folic acid supplementation for control of anemia in adolescent Nepalese girls . DESIGN R and omized controlled trial . SETTING A Government Girl School in Dharan , Nepal , an urban foothill town that is 305 m above sea level . SUBJECTS Consecutive healthy adolescent girls ( n = 209 , median age 15 years ) r and omized to 3 groups matched for age , anthropometry , and personal and sociodemographic characteristics . Of 209 subjects , 181 completed the trial . Two girls had adverse reactions to treatment and were excluded . INTERVENTION Group A ( n = 70 ) received a 350-mg ferrous sulfate and 1.5-mg folic acid combination once daily for 90 to 100 days . Group B ( n = 67 ) received the tablet under supervision once a week for 14 weeks . Group C ( n = 72 ) did not receive any drugs . OUTCOME VARIABLE Presupplementation and postsupplementation differences in prevalence of anemia and change in hematocrit . RESULTS Prevalence of anemia ( defined as hematocrit < 36 % ) declined from 68.6 % and 70.1 % in groups A and B to 20 % and 13.4 % , respectively , postsupplementation ( P<.001 ) , whereas the prevalence in group C changed little ( 68.1 % to 65.3 % , P = .81 ) . There was a significant rise in the mean hematocrit of both supplemented groups ( group A , 32.9 % + /- 3.5 % to 41.0 % + /- 5.6 % , P<.001 ; group B , 33.2 % + /- 3.6 % to 40.4 % + /- 4.9 % , P<.001 ) but no appreciable change in controls ( 34.2 % + /- 2.9 % to 34.1 % + /- 3.3 % , P = .91 ) . Net change in mean hematocrit in both the supplementation groups was comparable ( P = .57 ) . CONCLUSIONS The prevalence of anemia in adolescent Nepalese girls is high . Supervised iron and folic acid therapy once a week is an effective alternative to daily administration and helps lower the prevalence of anemia in adolescent girls A controlled trial of iron prophylaxis ( 3 ml intramuscular iron dextran ) to two-month-old infants was carried out on the north coast of Papua New Guinea where there is high transmission of malaria . The initial hypothesis was that iron deficiency increased susceptibility to infections and thus iron supplementation in a situation of actual or potential iron deficiency would diminish this susceptibility . Findings detailed elsewhere indicate that the placebo control group became relatively iron deficient and that the iron dextran group had adequate iron stores and a higher mean haemoglobin ; however , prevalence of malaria recorded in the field was higher in the iron dextran group . Analysis of field and hospital infectious morbidity in the trial indicated a deleterious effect of iron dextran for all causes and for respiratory infections ( the main single reason for admission ) . Total duration of stay in hospital was significantly increased in the iron dextran group . Analysis of other factors showed a deleterious effect of low weight for height at the start of the trial ; a significant positive correlation between birth haemoglobin and hospital morbidity rates and a positive interaction between haemoglobin and iron dextran on hospital morbidity . A possible association between malarial experience and other infectious morbidity is discussed This investigation deals with the dietary intakes and growth in early childhood in poor communities . Five hundred and forty five children , 9 - 36 months of age , and their caretakers ( mothers ) were selected r and omly and invited to participate in the study . The food and nutrient intake of children was assessed using a 10-item food frequency and amount question naire ( FAQ ) . The anthropometric nutritional status was assessed by the indices height-for-age ( H/A ) , weight-for-age ( W/A ) , weight-for-height ( Wt/Ht ) and MUAC , according to Indian and NCHS st and ards . The results showed that the intake of cereals , pulses , roots , green leafy vegetables ( GLVs ) , other vegetables , fruits , sugar , fats and oils among children was grossly inadequate . The nutrient intake for energy was 56 % of the current RDA . Anthropometric analysis revealed that the children were grossly undernourished . Seventy five per cent children were underweight ( < -2 SD ) , while 35 % severely undernourished ( < -3 SD ) . Approximately , 74 % children were having short stature ( chronic malnutrition ) with 39 % severely stunted . Nineteen per cent children were excessively thin ( wasted ) . The data regarding the degree of malnutrition among children demonstrated that 9.6 % girls in 9 - 36 months of age had severe malnutrition as compared to 6.5 % males . The maximum prevalence of severe malnutrition was in the age 31 - 36 months ( 10 % ) followed by 9.6 % in 13 - 18 months . The moderate degree of malnutrition was around 30 to 33 % in age group 13 - 36 months . The evidence from the study provides a strong basis to suggest low food intake as the main cause of under/malnutrition and growth retardation ( stunting ) in early childhood in poor communities The effect of chronic iron intake on diarrhoeal disease was evaluated in children in a community of low socio-economic stratum in Santiago , Chile . Children were incorporated into each of two consecutive cohorts ; each cohort was divided into two groups , one receiving iron-enriched milk ( 12 mg/l ) ( monthly average = 70 children ) and the other a control milk ( 1 mg/l ) ( monthly average = 83 children ) , and each cohort was followed up for 6 months . The incidence of diarrhoea was higher among the iron-supplemented children ( 30.4 vs 25.5 episodes/100 children/month , P < 0.025 ) . This was mainly due to results obtained in infants 3 - 8 months of age during the summer months . Supplemented infants had more bowel movements on day 1 ( P < 0.03 ) and liquid or semi-liquid stools were passed for more than 15 days more frequently ( P < 0.05 ) . While no differences were detected in aetiology , Shigella-associated episodes were less common among iron-supplemented infants ( P < 0.008 ) . Asymptomatic shedding of enteropathogens significantly increased in infants 12 - 18 months of age receiving iron-supplemented milk . In areas with inadequate environmental sanitation , chronic iron supplementation may have negative effects on diarrhoeal morbidity , despite improving iron nutritional status Oral iron supplementation is often routinely given to children with malaria-associated anaemia , but its contribution to recovery is controversial . A r and omized clinical trial , evaluating such routine , was carried out among 100 children , who had a haemoglobin of < or = 5 g/dl and a positive blood smear for malaria parasites . All children received malaria therapy ( chloroquin + fansidar ) and were r and omly allocated to two groups , one receiving additional oral iron treatment , the other being the control . In the 12-week follow-up period the haemoglobin level and malaria indices were measured at 2 , 4 , 8 , and 12 weeks . There was a 100 per cent compliance during the follow-up period . In each group 20 children ( 40 per cent ) required a blood transfusion . In the remaining 60 children , after 2 weeks the haemoglobin had risen 3.7 g/dl in the ferrous-supplemented group compared to 3.5 g/dl in the non-ferrous group . Thereafter , the increase in haemoglobin in both groups was steady . At follow-up measurements , the groups did not differ for haemoglobin levels . The mean haemoglobin at 12 weeks was 9.2 and 9.0 g/dl , respectively . It was concluded that iron supplementation did not have any effect on the rate of parasitaemia and on parasite density during the 12 weeks . However , the iron-supplemented group had a significantly increased morbidity from other causes than malaria . It appears that iron does not have an effect on the recovery of haemoglobin level in children with malaria-associated anaemia . This study provides no evidence supporting routine iron supplementation to these children OBJECTIVES To obtain baseline data on hemoglobin ( Hb ) levels of adolescent girls belonging to the low-socio-economic groups ; investigate the comparative efficacy of once ' weekly ' and ' daily ' administration of iron-folate tablets with respect to impact on the Hb levels ; and find out the effect of added ascorbic acid supplementation on the efficacy of iron-folate administration with respect to increment in Hb levels . DESIGN R and omized experimental . SETTING Adolescent girls of poor communities in urban areas of Delhi and rural parts of Bharatpur ( Rajasthan ) . METHODS The baseline investigations included measurements of height , weight , and Hb levels . The Hb levels of the participating subjects were measured again after 3 months and 6 months of supplementation . RESULTS 61.9 % of the subjects in the urban and 85.4 % in the rural area were anemic . The response of Hb levels to daily iron/folate supplementation was better in comparison to once-weekly supplementation . The increment in Hb levels of subjects due to addition of vitamin C to iron/folate supplementation was more than that with supplementation of iron/folate alone . CONCLUSIONS Considering compliance , feasibility and cost-factors , a public-health approach consisting of once-weekly distribution of iron/folate supplementation through schools and welfare centers is better and can be recommended as an appropriate strategy for combating anemia in adolescent girls of poor communities in developing countries like India AIMS Iron deficiency anaemia is associated , in observational studies , with developmental disadvantage . This study tested the hypothesis that feeding iron supplemented formula from 9 to 18 months of age would improve developmental performance . SUBJECTS AND METHODS 493 healthy children aged 9 months being fed pasteurised cows ’ milk were recruited from three UK centres . They were r and omised to : cows ’ milk as before , formula containing 0.9 mg/litre iron , or formula containing 1.2 mg/litre iron , until 18 months of age . Bayley mental and psychomotor developmental indices were measured at 18 months , as were growth and haematological indices . RESULTS Children fed iron fortified formula had higher plasma ferritin concentrations , but there were no significant intergroup differences in development or growth . CONCLUSIONS There are no developmental or growth advantages in children given iron supplemented formula , but a benefit for a minority who were anaemic , or the possibility that a benefit may emerge at a later age , can not be excluded OBJECTIVE To determine the efficacy of iron and zinc supplementation on behavior ratings of lead-exposed children . STUDY DESIGN In this double-blind , r and omized trial , 602 first- grade children received 30 mg ferrous fumarate , 30 mg zinc oxide , both , or placebo daily for 6 months . Lead , iron , and zinc status were determined at baseline and follow-up . Parents and teachers provided ratings of child behavior using the Conners Rating Scales . RESULTS The baseline mean ( SD ) blood lead concentration was 11.5 ( 6.1 ) mug/dL , with 51 % of children > or = 10 microg/dL. The prevalence of attention deficit hyperactivity disorder , estimated by combined parent and teacher ratings , was 6 % . At follow-up , parent ratings of oppositional , hyperactive , cognitive problems , and attention deficit hyperactivity disorder decreased by 1.5 , 1.2 , 2.5 , and 3.4 points , respectively ( P < .05 ) . Teacher ratings of hyperactivity increased by 1.1 points ( P = .008 ) , and the mean cognitive problem score declined by 0.7 points ( P = .038 ) . There were no treatment effects on mean change in scores , but children receiving any zinc had a higher likelihood of no longer receiving clinical ly-significant teacher ratings of oppositional behaviors . CONCLUSIONS This regimen of supplementation did not result in consistent improvements in ratings of behavior in lead-exposed children over 6 months UNLABELLED Iron supplementation programs using pediatric tablets or drops have not been successful in the control of anemia amongst infants and children in India . Sprinkles is an innovative multi-micronutrient home fortification strategy to control iron deficiency and anemia . OBJECTIVE We aim ed to determine the hematologic response to different doses and forms of iron in Sprinkles and iron drops . SETTING Twenty two villages of Vadu Rural Health Program , KEM Hospital , Pune . DESIGN Double blind clustered r and omized community-based trial . SUBJECTS Children ( n=432 ) aged 6 to 18 mo age with Hb between 70 to 100 g/L were enrolled . METHODS Selected villages were r and omized into 5 groups : Sprinkles 12.5 , 20 or 30 mg ferrous fumarate , Sprinkles 20 mg micronized ferric pyrophosphate or drops 20 mg ferrous glycine sulphate ( DROPS ) for 8 weeks . Household socio-demographic information was collected at baseline . Side effects and compliance were monitored through weekly visits . Hemoglobin was estimated at baseline , 3 and 8 weeks . Ferritin was assessed at baseline and 8 weeks . RESULTS Baseline characteristics were similar across all groups . Hemoglobin increased significantly ( P<0.0001 ) in all groups at 8 weeks with no difference between groups . Ferritin increased ( P<0.0001 ) significantly in all groups with no difference across the groups . Compliance ( overall range : 42 to 62 % ) was lowest for DROPS . Side effects were significantly higher among DROPS compared to Sprinkles ( p>0.05 ) . CONCLUSIONS Sprinkles 12.5 mg FF dose is as efficacious as higher doses of iron in Sprinkles or DROPS in increasing hemoglobin . Sprinkles FF 12.5 mg is recommended as it has fewer reported side effects and better compliance compared to DROPS OBJECTIVE To evaluate the impact of weekly treatment with ferrous sulfate on hemoglobin level , morbidity and nutritional status in a sample of anemic infants from Zona da Mata Meridional in the state of Pernambuco , Brazil . METHODS A controlled , community-based intervention was carried out with 378 infants who were followed-up for 18 months . Hemoglobin level was measured at 12 months in a total of 245 children r and omly selected . Participating infants were divided into three groups : two received 45 mg of elemental iron weekly , from 12 to 18 months of life ( 69 children with moderate/severe anemia , and 111 with mild anemia ) ; the third group was composed of 65 non-anemic children , who received no intervention . The remaining 133 children constituted the control group , for comparisons on nutritional status and morbidity . RESULTS The prevalence of anemia was 73.5 % at 12 months of life . After 6 months of treatment , 42.3 % of anemic children reached hemoglobin levels > or= 11.0 g/dL. The mean increase was 1.6 g/dL , being higher ( 2.5 g/dL ) in the group with lower levels of hemoglobin at baseline . Children without anemia at baseline received no treatment , and 40.3 % of them became anemic at the end of follow-up , with a mean decrease of 0.5 g/dL in hemoglobin levels . A significantly greater weight gain was observed in the two treated groups , while no significant improvements were seen in linear growth and duration of diarrhea . CONCLUSIONS The fact that less than half the children receiving ferrous sulfate recovered from anemia at the end of follow-up , along with the development of anemia in many untreated , previously non-anemic infants , suggests the need for effective control strategies Eighteen- to 60-month-old iron-deficient anemic children given iron therapy ( n = 25 ) and a control group matched for mother 's educational level showed no significant difference in mean mental development score at baseline . The control group 's mean score was increased significantly over baseline score at 3 and 6 months and was significantly higher than the experimental group 's mean score at 3 months . Although the experimental group demonstrated hematologic correction over 6 months , mean mental development score showed no significant improvement . Scores for an iron deficient not anemic group given iron ( n = 22 ) , despite complete hematologic correction over the six months of observation , and for its control group , did not change significantly . Baseline scores for an iron-deficient not anemic placebo group ( n = 23 ) and for its control group were not significantly different . At 3 months the control group score had increased significantly , whereas that for the experimental group had not . When experimental and control subjects were matched on baseline mental development score , the control subjects experienced increases in scores over time , further confirming an impaired ability to improve scores with repeated testing in the experimental groups . Behavioral rating data ( responsiveness to examiner , responsiveness to environment , and emotional tone ) revealed significant differences between the iron-deficient anemic group and its control group at 3 and 6 months , with the control group rated more responsive , suggesting that iron deficiency , alone or in association with anemia , may have some lasting effect on behavior and development . Group differences were also found between the mean number of occurrences of multiple stressful events . Failure to show improvement in scores in the iron-deficient anemic group may reflect the fact that those children were less testable than were children in the control group , despite repeated testings , a theory supported by the infant behavior rating data . This may be related to some irreversible behavioral deficit or to an adverse environmental milieu ( e.g. , stress ) In rural Mexico and in many developing countries micronutrient deficiencies , growth stunting , and morbidity from infectious diseases are highly prevalent in young children . We assessed the extent to which growth stunting could be reversed and the number of infectious disease episodes reduced by zinc and /or iron supplementation . In a double-blind , r and omized community trial 219 Mexican preschoolers were supplemented with either 20 mg Zn as zinc methionine , 20 mg Fe as ferrous sulfate , 20 mg Zn + 20 mg Fe , or a placebo . After 12 mo , plasma zinc increased significantly in the two zinc-treated groups , and plasma ferritin was significantly higher in the two iron-treated groups . There was no effect of treatments on growth velocity or body composition . Children in both zinc-supplemented groups had fewer episodes of disease ( zinc alone , 3.9 + /- 0.3 ; zinc+iron , 3.7 + /- 0.4 ; placebo , 4.6 + /- 0.5 ; P < 0.03 ) , including diarrhea ( zinc alone , 0.7 + /- 0.1 ; zinc+iron , 0.8 + /- 0.1 ; placebo , 1.1 + /- 0.2 ; P < 0.01 ) . Zinc and zinc+iron supplements reduced morbidity but had no effect on growth or body composition BACKGROUND Iron supplementation is recommended for children at high risk of anaemia , but its benefits may not outweigh the associated risk of malaria in areas of seasonal transmission . We investigated the effect on haemoglobin concentrations of intermittent administration of iron supplements and sulfadoxine-pyrimethamine in symptom-free children under intense health surveillance . METHODS In a trial of two by two factorial design , 328 anaemic Kenyan children were r and omly assigned either iron or placebo and sulfadoxine-pyrimethamine or placebo ( 82 to each group ) . Primary outcomes were haemological indicators of iron status and inflammation at the end of the follow-up , and occurrence of malaria attacks . Morbidity surveillance consisted of medical examinations every 4 weeks , continuous passive case detection , and visits twice a week to community health-workers . Analyses were by intention to treat . FINDINGS After 12 weeks , the groups assigned iron plus sulfadoxine-pyrimethamine , iron alone , or sulfadoxine-pyrimethamine alone had higher haemoglobin concentrations than the group assigned placebo ( treatment effect adjusted for prognostic factors at baseline : 11.1 g/L [ 95 % CI 7.5 to 14.7 ] ; 10.7 g/L [ 7.1 to 14.3 ] ; and 3.1 g/L [ -0.5 to 6.7 ] ) . Administration of iron plus sulfadoxine-pyrimethamine also lowered the proportion with anaemia from 100 % at baseline to 36 % at 12 weeks , and of iron deficiency from 66 % at baseline to 8 % at 12 weeks . Survival analysis showed no evidence of substantially increased risk of malaria after iron supplementation . INTERPRETATION Iron supplementation gives substantial health benefits , which may outweigh possible inherent risks caused by malaria . A larger study than ours is needed to assess benefits and risks of intermittent administration of sulfadoxine-pyrimethamine in reducing the incidence of malaria attacks in areas of seasonal malaria transmission BACKGROUND Previous studies on the cognitive effects of iron treatment have focused on anemic or non-anemic iron-deficient infants . The effect of iron supplementation on cognitive development among iron-sufficient infants has not been studied . The aim of the present study was to examine the effect of iron supplementation on performance in the Bayley Scales of Infant Development ( BSID ) and anthropometric measurement in 6-month-old iron-sufficient healthy infants . METHODS Healthy , iron-sufficient infants who were 6 months of age and were attending the Well Baby Clinic were considered for enrollment . Infants were r and omly assigned to take ferrous sulfate supplementation ( 1 mg/kg per day ) or no supplementation and were followed for 3 months . Anthropometric measurement , hematologic status and BSID were evaluated on admission and after 3 months . RESULTS Seven infants in the intervention group and nine in the control group completed the study . No significant differences were observed in anthropometric measurements and complete blood counts between the two groups after the 3 month study period . The mean transferrin saturation ( TS ) level decreased significantly in the control group during the study period ( from 15.3+/-2.6 to 7.8+/-5.1 % ; P = 0.0117 ) , but no such reduction was seen in the intervention group . At the end of the study , the TS of the control group was found to be significantly lower than that of the intervention group ( 7.8+/-5.1 vs. 19.9+/-7.9 % , respectively ; P = 0.0033 ) . The BSID scores of infants in both groups were within the normal range on admission and at the end of the study period . CONCLUSIONS Short-term iron supplementation did not change developmental test scores despite the hematologic response in iron-sufficient healthy infants . The high prevelance of iron-deficiency anemia and its relationship with adverse developmental outcome suggests that prevention of iron-deficiency anemia with prophylaxis needs to be emphasized , rather than treatment Malarial anemia is associated with a shift in iron distribution from functional to storage compartments . This suggests a relative deficit in erythropoietin production or action similar to that observed in other infections . Our study in Kenyan children with asymptomatic malaria aim ed at investigating whether malaria causes increased erythropoiesis , and whether the erythropoietic response appeared appropriate for the degree of result ing anemia . Longitudinal and baseline data were used from a trial with a 2 x 2 factorial design , in which 328 anemic Kenyan children were r and omly assigned to receive either iron or placebo , and sulfadoxine-pyrimethamine or placebo . Erythropoiesis was evaluated by serum concentrations of erythropoietin and soluble transferrin receptor . Prospect ively collected data showed that malarial infection result ed in decreased hemoglobin concentrations , and increased serum concentrations of erythropoietin and transferrin receptor . Conversely , disappearance of malarial antigenemia result ed in increased hemoglobin concentrations , and decreased concentrations of these serum indicators . Additionally , our baseline data showed that current or recent malarial infection is associated with increased serum concentrations of erythropoietin and transferrin receptor , and that these were as high as or perhaps even higher than values of children without malarial infection and without inflammation . Our findings indicate that in asymptomatic malaria , the erythropoietic response is adequate for the degree of anemia , and that inflammation probably plays no or only a minor role in the pathogenesis of the result ing anemia . Further research is needed to demonstrate the role of deficient erythropoietin production or action in the pathogenesis of the anemia of symptomatic malaria We evaluated the effect of one year of supplementation with iron plus zinc ( 12 mg/day of Fe+++ and 12.5 mg/day of Zn++ ) , zinc alone ( 12.5 mg/day of Zn++ ) and placebo on growth and on the iron , zinc , copper and selenium tissue contents in 30 well-selected children of short stature ( 16 M and 14 F ; 4 - 11 years old ) . Before and after supplementation , we measured the concentrations of iron , transferrin , ferritin , zinc and copper in serum , of zinc in erythrocytes and leukocytes , and of zinc , copper and selenium in hair , as well as glutathione peroxidase activity in erythrocytes . Before supplementation , ferritin and serum , erythrocyte and hair zinc contents were significantly lower than in age-matched controls , while the other measured indices were in the normal range . Iron plus zinc supplementation caused an improvement in growth rate in all subjects , i.e. , the median Z-score increased from -2.22 + /- 0.45 to -0.64 + /- 0.55 ; ( p < 0.01 ) . In the zinc-supplemented group , only the subjects whose ferritin levels were higher than 20 ng/L before supplementation showed a similar improvement of growth rate . Iron plus zinc supplementation could be a reasonable treatment in short , prepubertal children affected by marginal zinc and iron deficiency In 53 children with moderate iron deficiency ( haemoglobin 7,5 to 12 g/dl ) divalent iron salts as tablets ( 59Fe2 + -fumarate , -succinate , -sulfate ) were tested versus placebo ( controlled double-blind study ) . Gastrointestinal side effects were most frequently seen with iron succinate ( 50 % ) and iron sulfate ( 25 % ) . Therapeutic success as measured by haemoglobin regeneration was not significantly different among the three iron salts , but significantly more effective than in the placebo group . Children beyond the age of two years mostly refused the application of tablets and should be supplied with liquid preparations Aims : To determine the haematological effects of iron supplementation in predominantly breast fed term low birth weight ( LBW ) infants . Methods : Seventy three healthy term LBW ( < 2500 g ) , predominantly breast fed infants aged 50–80 days were r and omised into two groups to receive either iron ( 3 mg/kg/day ) ( iron supplemented ( IS ) group ; n = 37 ) or placebo drops ( placebo ( P ) group ; n = 36 ) . Haematological parameters and anthropometry were measured at baseline and repeated after four and eight weeks . Results : A total of 62 subjects ( 32 in the IS group and 30 in the P group ) came for the first follow up and 26 ( 13 in the IS group and 13 in the P group ) reported for the second visit . There were no significant differences in serum ferritin and anthropometry . However , covariates ( infant age , haemoglobin , and ferritin , and maternal haemoglobin ) adjusted haemoglobin change was significantly higher in the IS group after four weeks ( 4.6 g/l ; 95 % CI 0.5 to 8.8 ) and eight weeks ( 8.6 g/l ; 95 % CI 1.8 to 15.4 ) . Conclusions : Iron supplementation in a therapeutic dose in term breast fed LBW infants results in a marginal increase in haemoglobin . The functional benefit of this haemoglobin rise requires further evaluation To determine the clinical and laboratory effects of medicinal iron supplementation,602 healthy full-term infants were studied . Three hundred twenty-nine infants were given 30 mg . of elemental iron per day , and 273 were given a placebo . Fifty-five per cent of the original group completed the supplement program ( 11 months ) , and 46.5 per cent completed the total 18 months of the study period . Forty-one per cent were followed for a total of two years ; these infants were evaluated in detail . No objective benefit from the iron medication was found , but a transient decrease in the serum iron saturation was noted in the placebo group . Side effects were minimal . Subjectively the mothers of the iron-supplemented group had less complaints about their children 's sleep pattern or daytime irritability , and reported fewer illnesses . However , the more objective evidence of illnesses recorded in the infants ' charts did not support this difference . It is our belief that normal healthy infants who readily accept solid food will not be subject to iron deficiency anemia and do not benefit from iron supplementation Previous work at this hospital and elsewhere has shown that anaemia in toddlers is common and is associated with psychomotor delay . It seemed unclear , however , whether this association was cause and effect or merely due to the same underprivileged environment . A double blind r and omised intervention study was , therefore , performed . After an initial assessment 97 children with anaemia ( haemoglobin 8 - 11 g/dl ) aged 17 - 19 months received either iron and vitamin C or vitamin C only ( control group ) for two months and were then reassessed . The children who received the iron had an increased rate of weight gain and more of them achieved the expected rate of development . While iron deficiency anaemia is unlikely to be the only factor in the slower development of children living in underprivileged circumstances , it can at least be easily identified and treated . Routine child health surveillance in such areas should include a haemoglobin determination With the exception of iodine and Fe , there is still very limited information on the effect of micronutrients on cognitive function , especially among school-age children . The present analysis evaluates the relationship between dietary Fe , Zn and B vitamins ( B12 , B6 , folate and riboflavin ) and gains in cognitive test scores among school children in rural Kenya . Data for the present study were obtained from The Child Nutrition Kenya Project , a 2-year longitudinal , r and omised controlled feeding intervention study using animal source foods . Dietary nutrient values were based on monthly and bimonthly 24 h recall data collected during the study period . In longitudinal regression analyses , available Fe , available Zn , vitamin B12 and riboflavin showed significant relationships with improved cognitive test scores , after controlling for confounders such as energy intake , school , socio-economic status and morbidity . Available Fe intake was associated with significantly higher gains in Raven 's Coloured Progressive Matrices test scores over time . Available Zn intake was associated with significantly higher gains in digit span-total test scores over time , while vitamin B12 and riboflavin intakes were each associated with significantly higher gains in digit span-forward test scores over time . This analysis demonstrates the influence of improved dietary micronutrient status on school children 's cognitive function Four studies examined impacts of iron supplementation on school children of various ages and both sexes . The first study investigated impact of iron-folic acid supplements for 60 d on cognition in 94 boys and girls aged 5 - 8 y. Improvement in total scores of the anemics was significantly higher than the nonanemics in 7 - 8-y-old children only . The second study assessed impacts of supplementation on cognition in 14 pairs of 5 - 6-y-old anemic boys , with clear beneficial effects on cognitive function . The third study investigated effects of varying dosages of elemental iron on cognitive function in 48 boys aged 8 - 15 y , with different levels of improvement . The fourth study investigated impacts of iron supplementation on 163 anemic girls aged 8 - 15 y with treatment and evaluations at 4 and 8 mo , with significantly improved scores in cognitive function after the eighth month Abstract Objective : To compare the effect of unmodified cows ‘ milk and iron supplemented formula milk on psychomotor development in infants from inner city areas when used as the main milk source . Design : Double blind , r and omised intervention trial . Setting : Birmingham health centre . Subjects : 100 infants , mean age 7.8 months ( range 5.7 to 8.6 months ) , whose mothers had already elected to use unmodified cows ‘ milk as their infant 's milk source . Intervention : Changing to an iron supplemented formula milk from enrolment to 18 months of age , or continuing with unmodified cows ‘ milk . Main outcome measures : Developmental assessment s using Griffiths scales at enrolment and at 18 and 24 months . Results : 85 participants completed the trial . There were no significant differences in haemoglobin concentration between the two groups at enrolment , but by 18 months of age 33 % of the unmodified cows ‘ milk group , but only 2 % of the iron supplemented group , were anaemic ( P<0.001 ) . The experimental groups had Griffiths general quotient scores that were not significantly different at enrolment , but the scores in both groups declined during the study . By 24 months the decrease in the mean scores in the unmodified cows ‘ milk group was 14.7 whereas the decrease in the mean scores in the iron supplemented group was 9.3 ( P<0.02 , 95 % confidence interval 0.4 to 10.4 ) . Mean subquotient scores were considerably lower in the unmodified cows ‘ milk group at 24 months ; significantly so for personal and social scores ( P<0.02 , –5.4 to 17.2 ) . Conclusion : Replacing unmodified cows ‘ milk with an iron supplemented formula milk up to 18 months of age in infants from inner city areas prevents iron deficiency anaemia and reduces the decline in psychomotor development seen in such infants from the second half of the first year 1 . Behavioural responses of young anaemic Indian children to iron-folic acid supplements were assessed in two separate studies using the Indian adaptation of Wechsler 's ( 1967 ) intelligence scale for children ( WISC ) . 2 . The first study was an exploratory study in which the cognitive behaviour of 5 - 8-year-old children of both sexes was assessed before and after supplementation with 20 mg elemental Fe and 0.1 mg folic acid given daily for a period of 60 d. 3 . The supplemented children showed a significant improvement in haemoglobin ( Hb ) as well as the WISC scores while the control children who did not receive any supplements failed to show an improvement either in Hb or in the WISC scores . However , within the supplemented group when the initially-anaemic children were compared with the initially-non-anaemic ones , only the 7-year-old anaemic children performed significantly poor in the tests than the non-anaemic group of the same age . The study raised the possibility that in addition to increasing the blood Hb levels , Fe-folic acid supplements may have additional benefits in improving the cognitive performance of children . 4 . In the second study , cognitive behaviour of fourteen matched pairs of anaemic children in the age-range of 5 - 6 years was assessed before and after supplementation with 40 mg Fe and 0.2 mg folic acid given daily in two divided doses or sugar placebos for a period of 60 d. The tester did not know the groups to which each child belonged . 5 . The supplemented children showed a significant improvement in Hb as well as in the verbal and performance IQ of WISC . The control children showed no improvement in Hb but their verbal IQ improved significantly . However , there was no significant improvement in their performance IQ . 6 . The results indicated that Fe-folic acid supplements to anaemic children not only raised Hb levels but also improved intelligence test results , particularly in the performance section AIM To study impact of once weekly iron supplementation on praziquantel cure rate , Schistosoma haematobium reinfection , and haematological parameters in pupils aged between 9 and 15 years of age in Nchelenge district , Zambia . METHODS Pupils in the intervention group received once weekly dose of ferrous sulphate at 200 mg while those in the control received once weekly vitamin C at 100 mg for up to 9 months . Both study groups received a single dose of praziquantel at baseline . RESULTS S haematobium reinfection intensity was significantly lower in boys in the intervention group than in boys in the control group at 6 months ( P < 0.001 ) and 9 months ( P < 0.001 ) of supplementation . Significantly lower S haematobium reinfection intensity was found in girls in the intervention group than in girls in the control group only at 6 months of supplementation ( P = 0.018 ) . Boys in the intervention group were 42 % ( Adjusted Risk Ratio = 0.58 , 95 % confidence interval 0.39 , 0.86 ) less likely to be reinfected with S haematobium than in the control group at 6 months follow up . CONCLUSION Once weekly iron supplementation can decrease S haematobium reinfection after 6 months and should be incorporated into school based schistosomiasis control programs in highly endemic areas Thirty eight children with a haemoglobin concentration of 106 - 110 g/l were given either oral iron ( n = 17 ) or placebo ( n = 21 ) for two months . The treated group achieved a significantly higher rise in haemoglobin concentration ; in a quarter it was greater than 20 g/l . While those with the lower mean corpuscular volume and ferritin showed greater rises in haemoglobin these indices were of little value in predicting response in an individual child Geophagy has been associated with iron deficiency and anaemia , but no causal relationship has been established . To clarify this , we conducted a two-by-two factorial r and omised , controlled trial on the effect of iron and multimicronutrient supplementation on geophagy in Zambian schoolchildren in Lusaka , from February to December 2001 . Of the 406 children , 212 ( 52.2 % ) were girls and the mean ( range ) age was 10.2 ( 7 - 15 ) years . Geophagy was reported by 302 ( 74.4 % ) and more often in girls than in boys ( 80.2 vs. 67.7 % , P = 0.007 ) . The mean ( range ) daily earth intake was 25.2 ( 1 - 200 ) g. Geophageous children had more often geophageous relatives than non-geophageous children ( 79.5 vs. 1.9 % , P < 0.001 ) . Geophageous children had lower serum ferritin ( 20.5 vs. 25.0 microg/l , P = 0.032 ) but not haemoglobin ( Hb ) ( 129.2 vs. 130.4 g/l , P = 0.59 ) , than non-geophageous . Among those with Hb < 130 g/l , geophageous children had significantly higher prevalence ( 53.7 vs. 30.6 % , P = 0.024 ) of Ascaris lumbricoides infection than non-geophageous . The prevalence of geophagy ( 74.4 to 51.6 % ) and the intake of earth ( 25.3 to 15.0 g/day ) declined ( P = 0.001 and P < 0.001 , respectively ) among the 220 ( 54.2 % ) children followed-up . In bivariate analysis , non-iron supplementation reduced the prevalence of geophagy more than iron supplementation did , but this was not confirmed in the multiple logistic regression analysis . Multimicronutrients had no effect on either geophagy prevalence or earth intake . Geophagy was prevalent and associated with iron deficiency , but iron supplementation had no effects on geophageous behaviour . Geophagy could be a copied behaviour and the association between geophagy and iron deficiency due to impaired iron absorption following earth eating We evaluated the effect of weekly doses of 400 mg of ferrous sulphate for 4 months on the iron status of adolescent girls in a controlled trial in Tanga , Tanzania . Supplementation led to a significantly greater increase in serum ferritin compared with the control group ( + 15.6 microg/l vs. 8.6 microg/l ) ( P = 0.002 ) but there was no significant difference in change in haemoglobin . Children given iron showed a significantly greater weight gain than controls ( + 2.4 kg vs. + 1.4 kg ) ( P = 0.03 ) . Weekly iron supplementation may be an effective means of increasing iron stores and growth in children vulnerable to iron deficiency Adult males and children between 4 and 12 years in a subsistence farming community in The Gambia were screened for haematological status . 80 men and 80 children with initially poor status were identified and allocated to three treatment groups comprising : a placebo , ferrous sulphate , and ferrous sulphate with riboflavin . Over a period of 6 weeks of supplementation there was a general improvement in haematological status in the two supplemented groups . The inclusion of riboflavin in the supplement enhanced recovery , particularly in those individuals with strikingly low levels of haemoglobin at the outset In sub-Saharan countries , although malaria and malaria-associated anaemia are major public health problems , the usefulness of supplementary iron treatment for children with malaria-associated anaemia is unknown . In a 6-week period during the 1995 rainy season , 222 Malawian children aged < 5 years , who sought treatment for malaria , had > or = 500 parasites/microliter blood and at least 5 g haemoglobin (HB)/dl blood and whose parents gave consent , were r and omized into a prospect i ve study comparing the efficacy of sulphadoxine- pyrimethamine only ( SP ) , SP plus daily iron ( SPD ) and SP plus weekly iron ( SPW ) as treatment for malaria-associated anaemia . The patients had their HB concentrations measured on enrollment ( day 0 ) , just before antimalarial treatment , and on days 3 , 7 , 14 , 21 and 28 ; 215 ( 96.8 % ) completed the 28-day study . Among the children with 5 - 8 g HB/dl on enrolment , HB gain by the end of the study was significantly greater than in the children with > 8 g HB/dl initially ( 4.1 v. 2.2 g/dl ; P < 0.05 ) , and those in the SPD group gained significantly more HB by days 21 and 28 ( 3.6 and 4.9 g/dl , respectively ) than those in either the SPW ( 2.7 and 3.7 g/dl , respectively ) or the S2 groups ( 2.6 and 3.5 g/dl , respectively ) ; there was no difference in HB gain between the SP and SPW groups . Type of treatment had no apparent effect , at any time during the study , on HB gains in those patients who had > 8 g HB/dl on enrolment . Thus the children with 5 - 8 g HB/dl on enrolment benefited from daily iron therapy whereas those with > 8 g HB/dl derived no significant benefit ; improvement in HB depended most on whether enrolment HB was < or = 8.0 g/dl . As treatment with an effective antimalarial drug result ed in HB gains , irrespective of treatment group or HB concentration at enrolment , the anaemia observed may be mostly related to malaria . However , as a larger proportion of the iron-treated patients failed to clear their parasitaemias than of those given SP alone , oral iron may inhibit SP action . It is therefore recommended that , for children with both malaria and malaria-associated anaemia , the malaria should first be cleared with an effective antimalarial drug , such as SP , before the anaemia , if it still persists , is treated with iron The present study was carried out to find out the prevalence and etiology of nutritional anaemia among preschool children from an urban slum . R and omly selected 300 children aged 3 months-3 yr were analysed over a period of one year for estimating prevalence of nutritional anaemia . Prevalence was also assessed by the rise in haemoglobin after 8 wk of haematinic supplementation in 159 of the 300 subjects . Ninety anaemic children were evaluated for the etiology of anaemia . Prevalence of anaemia , as judged by WHO recommended ' cut-off ' value of haemoglobin < 11 g/dl , was 76 per cent while comparable value of 74.8 per cent was derived by response to haematinic supplementation . Pure iron deficiency anaemia ( IDA ) was detected in 41.4 per cent ( 37/90 ) of anaemic children . Vitamin B12 deficiency alone or in combination with iron was diagnosed in 14.4 and 22.2 per cent anaemic children respectively . Similarly folate deficiency , IDA with infection and anaemia of chronic diseases ( ACD ) was diagnosed in 2.2 , 3.3 and 12.2 per cent cases respectively . Childhood anaemia continues to be a significant public health problem in preschoolers and iron deficiency is by far the commonest nutritional cause of anaemia . Vitamin B12 deficiency per se or in combination with iron is an important yet not commonly recognised cause of anaemias in preschool children in the community Iron and zinc deficiencies are common in developing countries and supplementation is one way of reversing these deficiencies . The objective of this r and omized , placebo-controlled clinical trial was to identify the effect of daily supplementation with iron , zinc , and iron plus zinc on the morbidity experience of 855 children 0.5 - 15 years of age in Peru . Single nutrient supplementation with zinc reduced diarrhea morbidity by 23 % in all children . In older children ( more than five years of age ) , iron supplementation increased morbidity due to Plasmodium vivax and diarrhea . In younger children , iron combined with zinc provided protection against P. vivax malaria , but also interfered with some of the diarrhea protection associated with zinc supplementation . No statistically significant effect was observed of either supplement on incidence of respiratory infection or anthropometric indices . Iron and zinc deficiencies should be remedied , and combined supplementation may be a good option , particularly in younger children in P. vivax malaria-endemic areas , although local endemicity and species-specific prevalence should be considered carefully when design ing any supplementation program involving iron in a malaria-endemic area Anemia-specific mortality was markedly elevated among refugee children < 5 years of age in Tanzania . In a r and omized , double-blind study , 215 anemic children were initially treated for malaria and helminth infection and then received 12 weeks of thrice-weekly oral iron and folic acid . Group I received placebo and chloroquine treatment for symptomatic malaria infection ( i.e. , no presumptive anti-malarial treatment given ) . Group II received placebo and monthly presumptive treatment with sulfamethoxazole-pyrimethamine ( SP ) . Group III also received monthly SP and thrice-weekly vitamins A and C ( VAC ) . Mean hemoglobin concentration increased from 6.6 to 10.2 g/dL , with no significant differences among groups . Group II had lower mean serum transferrin receptor levels ( TfR ) than group I [ P = 0.023 ] . A greater proportion of participants in group III had normal iron stores ( TfR < 8.5 microg/ mL ) than in group II [ P = 0.012 ] . Initial helminth and malaria treatment , followed by thrice-weekly iron and folic acid supplements result ed in increased hemoglobin levels . Monthly SP and thrice-weekly VAC contributed to improve iron stores . Monthly SP may have a role in situations where asymptomatic disease is prevalent or where access to care is limited . Because administration of VAC also hastened recovery of iron stores over administration of monthly SP alone , health care personnel could add VAC to the treatment for moderate anemia if maximum recovery of iron stores is desired A r and omized controlled trial in KwaZulu-Natal ( South Africa ) of 428 primary -school pupils ( stratified into 6 groups by age , sex and intervention ) measured the effect of different anthelmintic treatments and iron supplementation regimens provided twice at 6-monthly intervals for 1 year ( 1996/97 ) . Half the pupils received iron supplementation ( ferrous fumarate 200 mg weekly for 10 weeks ) . Pupils received 2 anthelmintic regimens , either ( i ) albendazole 400 mg plus praziquantel 40 mg/kg or ( ii ) albendazole 400 mg on 3 consecutive days plus praziquantel 40 mg/kg or ( iii ) placebo . Baseline prevalences of Ascaris 55.9 % , Trichuris 83.6 % , hookworm spp . 59.4 % , were reduced after 12 months for single-dose albendazole treatment to Ascaris 17.4 % ( P < 0.005 ) , Trichuris 61.5 % ( NS ) , hookworm spp . 0 % ( P < 0.005 ) , and for triple-dose albendazole treatment to Ascaris 14.8 % ( P < 0.005 ) , Trichuris 25.0 % ( P < 0.01 ) , hookworm 0 % ( P < 0.005 ) . Schistosoma haematobium 43.4 % was reduced among treated groups to 8.3 % ( P < 0.005 ) . There were no significant changes in the anthropometry of the different treatment groups at either 6 or 12 months post treatment . Twelve months after treatment there was a significant increase in haemoglobin levels ( P = 0.02 ) among pupils receiving triple-dose albendazole , praziquantel and ferrous fumarate ; pupils receiving no anthelmintic treatment showed a significant decrease as did pupils who received triple-dose albendazole and praziquantel but no iron . Regular 6-monthly anthelmintic treatment significantly reduced the prevalence of Ascaris , hookworm spp . and S. haematobium infections ( P < 0.05 ) . Triple-dose treatment for Trichuris was significantly more effective than a single dose of albendazole 400 mg ( P = 0.002 ) . In areas with schistosomiasis , hookworm infection and high prevalence of Trichuris infection , combination treatment with praziquantel , triple-dose albendazole , plus iron supplementation , is likely to improve pupils ' health and haemoglobin levels The effect of a combined supplement of iron , thiamine , riboflavin and vitamin C on malarial incidence in 5 to 14-year-old children was tested in a malnourished rural community in a region of The Gambia noted for high prevalence of malaria during the rainy season . 190 children , divided into 2 matched groups , received either the supplement or a matching placebo for 3 months . No significant difference in malarial incidence was observed between the 2 groups , despite a major improvement in biochemical indices of nutrient status in the supplemented group , especially for riboflavin and vitamin C. Severity of episodes was also similar between groups , but in subjects who developed parasitaemias there was a trend towards higher parasite counts in those receiving the active supplement . Nutritional interventions in malarious areas may have adverse effects on malaria , and the increase in parasitaemia was compatible with the hypothesis that a small but significant reduction in defences had occurred . However , the absence of increases in the incidence of proven malaria cases and their severity must also be taken into account , in order to make a balanced assessment of the possible increase in risk . Further investigations are needed to measure the risk in benefit rates , and to consider the effects of individual nutrients in isolation This double-blind clinical trial was conducted in Thail and to assess the impact of iron treatment on the IQ and educational attainment of 1358 9 - 11-y-old children . The children were classified into one of three groups : iron replete , iron depleted , and iron-deficient anemic . The Raven Progressive Matrices was used to measure IQ . A Thai language and a math test were administered to assess school attainment . A 50-mg/d tablet of ferrous sulphate was given for 2 wk and a 100 mg/d tablet , for 14 wk . An anthelminthic drug was given on the day of the blood test before treatment and 3 mo after the intervention started . There is evidence of a positive association between iron status and IQ and a language school achievement test but there is no support for the internal validity of the hypothesis that this association is causal OBJECTIVE A community-based , r and omized trial was design ed to compare the effect of nutrition education and /or iron supplementation ( weekly ) on iron status of children in an urban slum in Delhi . METHODS Four hundred and fifty one children , 9 - 36 months of age and their caretakers ( mothers ) , assigned to one of the following groups were included in the cohort . Group 1 , nutrition education . Group 2 , supplementation ( with 20 mg elemental iron ) . Group 3 , nutrition education with supplementation ( with 20 mg elemental iron ) and Group 4 , control given placebo . The intervention program was of four months duration , with a treatment phase of 8 wk followed by 8 wk of no treatment . RESULTS Post intervention , at 8 wk and at 16 wk , the hemoglobin change in the nutrition education , supplementation , nutrition education with supplementation and control groups was 2.9 , 1.9 , 3.8 and -5.9 % , respectively and 2.1 , -1.9 , 0 and -9.3 % , respectively ( as compared to initial values ) . There was no significant effect of any of the intervention at 8 weeks . At 16 wk , there was significant positive effect of nutrition education group ( p less than 0.05 ) . The percent change in serum ferritin value at 16 wk in the nutrition education , supplementation , nutrition education with supplementation and control groups was 5.7 , -2.3 , -3.4 and -40 % , respectively . Serum ferritin values were significantly higher for the nutrition education group ( p < 0.001 ) as compared to the control . At 16 wk , the nutrition education group mothers showed significantly higher nutrition knowledge and the dietary iron intake of children was significantly higher than their control group counterparts ( p < 0.0001 ) . CONCLUSION The study suggests that nutrition education did have a positive effect on the iron status possibly by improving the dietary iron intake OBJECTIVE To assess the effect on the haemoglobin concentrations of schoolchildren of weekly iron tablets administered by teachers . DESIGN Sixty schools were r and omly assigned to two groups : in 30 schools children were given weekly for 10 weeks a tablet providing 65 mg of iron and 0.25 mg of folic acid ; in the other 30 schools no iron tablets were given . All children were dewormed and given vitamin A before the study began . The haemoglobin concentration of up to 20 r and omly selected children in each school was estimated before and 2 weeks after the end of treatment . SETTING Rural community schools in Kolondieba district of Mali . SUBJECTS Some 1113 schoolchildren aged 6 - 19 years with a mean of 11.4 years . RESULTS The haemoglobin concentration of treated children rose on average by 1.8 g l(-1 ) and the prevalence of anaemia fell by 8.2 % ; in untreated children the haemoglobin concentration fell by an average of -2.7 g l(-1 ) and the prevalence of anaemia rose by 9.4 % . The fall in haemoglobin concentration among untreated girls of -4.0 g l(-1 ) was greater than in untreated boys ( -0.3 g l(-1 ) ) . CONCLUSIONS Weekly iron tablets given by teachers prevented a general fall in the haemoglobin concentrations of untreated children , and led to a small but statistically significant rise among treated children . Young children benefited more than children aged > or=12 years , and girls benefited more than boys A double-blind clinical trial was conducted among 9- to 11-year-old children in sixteen schools in the Chon Buri province of Thail and to assess the effects of an iron supplement combined with an anthelminthic agent ( i.e. albendazole ) . In addition to the albendazole , Fe or placebo tablets were distributed to 2268 children enrolled in grade s three to five without knowledge of the Fe status of the children . Criteria for case inclusion were : ( a ) absence of A E Bart 's or haemoglobin ( Hb ) H disease , ( b ) absence of abnormal Hb EE , and ( c ) age , 108 - 144 months . The results showed a significant improvement in the Fe status of the children after 16 weeks of treatment . The increments were : Hb from 124 to 128 g/l , serum ferritin from 34.54 to 104.72 micrograms/l , transferrin saturation from 24.09 to 35.05 % ; free erythrocyte protoporphyrin decreased from 444.7 to 281.4 micrograms/l erythrocytes . These changes were significantly greater than in the control group that received only the anthelminthic agent . However , the administration of albendazole only also result ed in significant changes in the same Fe indicators The optimum management of children with severe malarial anaemia is still uncertain . Hence , we have undertaken a study to determine whether iron treatment is as effective at restoring haemoglobin levels one month after presentation as blood transfusion without iron treatment in children with moderately severe malarial anaemia . Two hundred and eighty-seven children with a packed cell volume ( PCV ) < 15 % and malaria infection were recruited into the study ; 173 children were assigned to receive blood transfusion because they had a PCV < 12 % and /or signs of respiratory distress and the remaining 114 children were allocated at r and om to receive either blood transfusion ( 58 ) or treatment with oral iron ( 56 ) for 28 d. Twenty-four children died , 23 in the most severely anaemic group . Fifteen children ( 65 % ) died before transfusion was given and most deaths occurred within the first 4 h of admission . One child died in the iron treatment group and 10 subsequently required transfusion . Among the severely anaemic children , those with respiratory distress were at greater risk of death than those without respiratory distress . After 28 d , haematological restoration was significantly better in children who had received iron than in those treated by blood transfusion ( P = 0.02 ) . Children who received malaria chemoprophylaxis after discharge from hospital had fewer episodes of malaria and subsequent admissions to a hospital or health centre than those who did not . Children with severe anaemia and clinical signs of respiratory distress must be identified quickly and transfused as soon as possible . However , for less severely anaemic children who are clinical ly stable , iron therapy offers an alternative to transfusion provided such children can be kept under surveillance and transfused subsequently should this become necessary 1 . The effect of daily supplements of 20 - 30 mg inorganic iron as ferrous sulphate on the growth , activity and haematological status of preschool children was studied for 3.5 , 7 and 12 months and compared to that of children who served as controls . All children were given their daily requirements of energy and protein . In addition , they received 5 microgram cyanocobalamin and 200 microgram folic acid . 2 . Fe supplementation increased the haemoglobin , serum Fe and percentage saturation of transferrin and reduced the unsaturated Fe-binding capacity significantly compared to corresponding values for the controls . 3 . Height and activity were unaffected by Fe supplements . 4 . Of the children 45 % had haemoglobin values below 110 g/l at the end of 7 - 12 months of Fe supplementation In a prospect i ve cohort study of 196 infants from birth to age 15 mo , the relationship of iron status to psychomotor development , the effect of a short-term trial of oral iron or placebo , and the effect of longer-term oral iron therapy was assessed . Development was assessed with the Bayley Scale of Infant Development in anemic , nonanemic , iron-deficient , and control children . Anemic infants had significantly lower indices than did control or nonanemic , iron-deficient infants . Control infants and nonanemic , iron-deficient infants performed comparably . No difference between the effect of oral administration of iron or placebo was noted after 10 d or 3 mo of iron therapy . A hemoglobin concentration of less than 105 g/L and anemia duration greater than 3 mo were correlated with significantly lower motor and mental scores , suggesting that when iron deficiency progresses to anemia , adverse influences in the performance of developmental tests appear and persist , despite iron therapy This experimental study was design ed to investigate the effects of daily versus intermittent iron supplementation on iron status of high school girls in Zahedan and Rasht cities in 1996 - 1997 . The subjects were selected r and omly from among students of grade s 1 - 3 of four high schools in each city . Anemia was determined by measuring hematological indices . 260 anemic and a similar number of non-anemic subjects of 4 high schools were selected and allocated r and omly to 4 treatment groups . During a 3-month period , the test groups were given 150 mg ferrous sulfate tablets ( 50 mg Fe ) . Subjects in group 1 received a daily dose , groups 2 & 3 received twice or once weekly doses respectively . The control group received no iron supplement . For these subjects , in addition to hematological indices biochemical iron indices were measured in the beginning and at the end of the study . The increases in hemoglobin concentration in anemic subjects were not significantly different among supplemented groups but were different from the control group ( p < 0.00001 ) . Among anemic subjects , changes in serum ferritin levels in 3 supplemented groups were significantly different from the control group . Serum ferritin in Group 1 was also increased to a greater extent than groups 2 and 3 ( P < 0.00001 ) . It is concluded that over the study period a weekly iron dose was as effective as a daily dose in treating anemia but the daily dose was more effective in improving iron stores than a weekly dose in the short run Whether administration of folic acid to children with malaria anemia is helpful is controversial . Therefore , we conducted a r and omised , placebo-controlled trial of 14 days of treatment with folic acid ( 1 mg/d ) in Zambian children with malaria anemia treated with either sulfadoxine/pyrimethamine ( SP ) or atovaquone/proguanil ( AP ) . Among children who received SP , the prevalence of parasitemia was higher in children treated with folic acid than among those given placebo at days 3 , 7 , and 14 after the start of treatment , and the difference at day 3 was statistically significant ( P = 0.013 ) . Folic acid treatment had no effect on parasitemia in children treated with AP . Administration of folic acid led to a small increase in packed cell volume over that seen in the placebo group at days 14 and 28 after the start of treatment OBJECTIVES To examine the effectiveness of weekly iron supplements given for 10 weeks by teachers to children in rural schools in the Philippines . METHODS Forty-nine rural primary schools took part in the study and were r and omly assigned to two groups : children in 25 schools received a weekly tablet providing 108 mg iron while children in 24 schools acted as controls . All children were dewormed before the start of the iron supplementation . The haemoglobin concentration of a systematic sample of one in three children in two classes in each school was estimated before and 5 - 17 weeks after the end of the iron supplementation . RESULTS A total of 1510 children aged 7 - 12 years were studied at both surveys . The mean haemoglobin concentration of children in the intervention group did not change significantly ; in the untreated group it fell by 3.8 g/l and the prevalence of anaemia rose from 14.3 % to 25.6 % . The difference between study groups was significantly larger amongst the younger children ( 7 - 8 years ) , and was observed in both anaemic and non-anaemic children . CONCLUSION Even where anaemia is only a mild public health problem , weekly iron supplements given by teachers may prevent a fall in the haemoglobin concentration , and can benefit both anaemic and non-anaemic children BACKGROUND Up to 25 % of adolescent girls in the USA are iron deficient . This double-blind , placebo-controlled clinical trial assessed the effects of iron supplementation on cognitive function in adolescent girls with non-anaemic iron deficiency . METHODS 716 girls who enrolled at four Baltimore high schools were screened for non-anaemic iron deficiency ( serum ferritin < or = 12 micrograms/L with normal haemoglobin ) . 98 ( 13.7 % ) girls had non-anaemic iron deficiency of whom 81 were enrolled in the trial . Participants were r and omly assigned oral ferrous sulphate ( 650 mg twice daily ) or placebo for 8 weeks . The effect of iron treatment was assessed by question naires and haematological and cognitive tests , which were done before treatment started and repeated after the intervention . We used four tests of attention and memory to measure cognitive functioning . Intention-to-treat and per- protocol analyses were done . FINDINGS Of the 81 enrolled girls with non-anaemic iron deficiency , 78 ( 96 % ) completed the study ( 39 in each group ) . Five girls ( three control , two treatment ) developed anaemia during the intervention and were excluded from the analyses . Thus , 73 girls were included in the per- protocol analysis . Ethnic distribution , mean age , serum ferritin concentrations , haemoglobin concentrations , and cognitive test scores of the groups did not differ significantly at baseline . Postintervention haematological measures of iron status were significantly improved in the treatment group ( serum ferritin 27.3 vs 12.1 micrograms/L , p < 0.001 ) . Regression analysis showed that girls who received iron performed better on a test of verbal learning and memory than girls in the control group ( p < 0.02 ) . INTERPRETATION In this urban population of non-anaemic iron-deficient adolescent girls , iron supplementation improved verbal learning and memory This prospect i ve , double-blind , placebo-controlled trial was design ed to study the effect of iron therapy on the growth of iron-replete and iron-deficient children , and to study the change in iron status in iron-deficient children with iron therapy . One hundred and fifty children ( aged 6 - 24 months ) were included in the study . After an informed written consent , 100 healthy children , who were iron replete ( group I ) according to preset criteria , were r and omly allocated to receive iron supplements 2 ng/kg/day ( group IA ) or placebo ( group IB ) . Fifty iron-deficient children ( group II ) were administered iron syrup 6 mg/kg/day . Growth parameters ( weight , length and head-circumference ) and hematological parameters were studied for 4 months . Iron therapy , as compared with placebo , produced a significant improvement of mean monthly weight gain ( p < 0.001 ) and linear growth ( p < 0.001 ) in the iron-deficient children . However , it significantly decreased the weight gain ( p < 0.001 ) and linear growth ( p < 0.001 ) of iron-replete children . Caution should therefore be exercised while supplementing iron to children with apparently normal growth and when the iron status of the child is not known The prevalence of anemia is high in adolescent girls in India , with over 70 % anemic . Iron-folic acid ( IFA ) supplements have been shown to enhance adolescent growth elsewhere in the world . To confirm these results in India , a study was conducted in urban areas of Vadodora , India to investigate the effect of IFA supplements on hemoglobin , hunger and growth in adolescent girls 10 - 18 y of age . Results show that there was a high dem and for IFA supplements and > 90 % of the girls consumed 85 out of 90 tablets provided . There was an increment of 17.3 g/L hemoglobin in the group of girls receiving IFA supplements , whereas hemoglobin decreased slightly in girls in the control group . Girls and parents reported that girls increased their food intake . A significant weight gain of 0.83 kg was seen in the intervention group , whereas girls in the control group showed little weight gain . The growth increment was greater in the 10- to 14-y-old age group than in the 15- to 18-y-old group , as expected , due to rapid growth during the adolescent spurt . IFA supplementation is recommended for growth promotion among adolescents who are underweight Malaria and anemia are common conditions in patients presenting to outpatient clinics in Kenya . Anemia is usually due to malaria infection with underlying micronutrient deficiency . Iron therapy has been shown to enhance recovery from anemia in children with malaria , without affecting malaria treatment . Iron and folic acid are often prescribed together for anemic individuals . Until recently in Kenya , the drug of first choice for non-severe malaria was sulfadoxine-pyrimethamine ( SP ) , an antifolate antimalarial drug . In this study , 303 patients of all ages with anemia and uncomplicated Plasmodium falciparum malaria attending an outpatient clinic in an area of seasonal malaria were treated with SP and iron , and were r and omized to receive folic acid . Parasite clearance rates were measured using a survival analysis plot for both parasitologic and clinical failure . There was a significant reduction in the efficacy of SP in patients taking st and ard therapeutic doses of folic acid using the survival curve for parasitologic failure ( P < 0.0001 ) , but no difference for clinical failure ( P = 0.7008 ) . Folic acid supplementation did not enhance recovery from anemia The efficacy of iron supplementation for iron-deficient subjects is in no doubt . However , the assumption that iron supplementation of iron-replete subjects is harmless may not be valid . We have studied the effect of iron supplementation on growth rate in 47 iron-sufficient young children ( 12 - 18 months ) in Indonesia . The children were r and omly assigned either ferrous sulphate ( 3 mg/kg daily ) or placebo every day for 4 months . Before treatment the length , weight , and arm circumference of the two groups were similar . During the 4 months of supplementation the rate of weight gain was significantly greater in the placebo group than in the iron-supplemented group ( 0.106 [ SE 0.010 ] vs 0.070 [ 0.011 ] kg every 2 weeks , p = 0.02 ) . The rates of gain in length and arm circumference did not differ significantly by treatment . There were no differences between the groups in rates of respiratory and gastrointestinal infections . These results suggest that iron supplementation of iron-replete children may retard their growth OBJECTIVE The objective was to study the effects of iron supplementation on hemoglobin and iron status in 2 different population s. STUDY DESIGN In a r and omized , placebo-controlled , masked clinical trial , we assigned term Swedish ( n = 101 ) and Honduran ( n = 131 ) infants to 3 groups at 4 months of age : ( 1 ) iron supplements , 1 mg/kg/d , from 4 to 9 months , ( 2 ) placebo , 4 to 6 months and iron , 6 to 9 months , and ( 3 ) placebo , 4 to 9 months . All infants were breast-fed exclusively to 6 months and partially to 9 months . RESULTS From 4 to 6 months , the effect of iron ( group 1 vs 2 + 3 ) was significant and similar in both population s for hemoglobin , ferritin , and zinc protoporphyrin . From 6 to 9 months , the effect ( group 2 vs group 3 ) was significant and similar at both sites for all iron status variables except hemoglobin , for which there was a significant effect only in Honduras . In Honduras , the prevalence of iron deficiency anemia at 9 months was 29 % in the placebo group and 9 % in the supplemented groups . In Sweden , iron supplements caused no reduction in the already low prevalence of iron deficiency anemia at 9 months ( <3 % ) . CONCLUSION Iron supplementation from 4 to 9 months or 6 to 9 months significantly reduced iron deficiency anemia in Honduran breast-fed infants . The unexpected hemoglobin response at 4 to 6 months in both population s suggests that regulation of hemoglobin synthesis is immature at this age The growth status of anemic ( n = 117 , Hb 7 - 10 g/dl ) and normal ( n = 53 , H > or = 11 g/dl ) children 3 - 5 years of age living under similar environmental and socio-economic conditions was evaluated . The dietary intake was assessed on a r and om sub sample of the anemic and normal children . The anemic children had a poorer growth status than normal children as indicated by their significantly ( p < 0.001 ) lower body weight , height and weight for age and significantly ( p < 0.001 ) larger number in Grade s II and III malnutrition . Iron supplementation ( 40 mg elemental iron/day ) for six months produced a significant ( p < 0.001 ) increase in Hb levels of both groups ( 1.6 g/dl in the anemic and 0.8 g/dl in the non-anemic ) compared to their respective controls who received sugar placebos . The growth performance of the anemic children supplemented with iron was superior to that of anemic placebo treated children as indicated by a better weight gain and a significantly higher weight for height ( p < 0.05 ) . Weight for age was a good differentiator of the anemic from normal while weight for height was a good indicator of the impact of iron supplements on growth Concern has been raised that iron supplementation for treatment of acute malaria may worsen the severity of malaria . We compared the effect of iron and folate with folate alone on hematologic recovery in children treated for acute malaria . We r and omized 82 children 6 - 60 months of age from Nigeria with smear-positive malaria and anemia ( hematocrit < 33 % ) to receive iron ( 2 mg/kg/day ) plus folate ( 5 mg/day ) or folate alone in addition to antimalarial drugs . The mean ± SD hematocrit at baseline was 28.5 % ± 2.9 % . At four weeks , the mean hematocrit increased by 2.5 % ± 1.6 % in the iron plus folate group and by 1.4 % ± 1.0 % in the folate alone group ( P = 0.001 ) . Baseline hematocrit , iron supplementation , weight for height , and weekly meat intake were significant predictors of final hematocrit . The effect of iron was not significantly modified by baseline hematocrit , weekly meat intake , nutritional status , mother 's education , sex , or age of the child . Iron supplementation improved hematologic recovery in children with malarial anemia Anemia is common among children in sub-Saharan Africa and its etiology is multifactorial . Likely causes of anemia are low bioavailability of dietary iron , malaria , and helminth infection . In this study , we aim ed to assess the effect of iron fortification , intermittent preventive treatment ( IPT ) of malaria , and anthelmintic treatment on hemoglobin concentration and anemia prevalence among school children . The study was a 6-mo , r and omized , double-blind , controlled trial enrolling 591 6- to 14-y-old school children in Côte d'Ivoire using the following : 1 ) iron-fortified biscuits providing an additional 20 mg iron/d as electrolytic iron 4 times/wk ; 2 ) IPT of malaria with sulfadoxine-pyrimethamine at 0 and 3 mo ; and 3 ) anthelmintic treatment at 0 and 3 mo as the interventions . Prevalence of anemia , iron deficiency , malaria parasitemia , and helminth infection was 70.4 , 9.3 , 57.7 , and 54.8 % , respectively . Iron fortification did not improve iron status , IPT of malaria did not affect malaria burden , and neither had an impact on anemia prevalence . Anthelmintics significantly reduced the burden of helminth infections and decreased anemia prevalence ( odds ratio : 0.4 , 95 % CI : 0.3 , 0.7 ) . The low prevalence of iron deficiency and an extended dry season that decreased malaria transmission likely reduced the potential impact of iron fortification and IPT . In this setting , anthelmintic treatment was the only intervention that modestly decreased rates of anemia |
13,590 | 11,412,287 | There was a lack of evidence for any anti-pruritic efficacy with prophylactic propofol , epidural or intrathecal epinephrine , epidural clonidine , epidural prednisone , intravenous ondansetron , or intramuscular hydroxyzine .
CONCLUSION Naloxone , naltrexone , nalbuphine and droperidol are efficacious in the prevention of opioid-induced pruritus ; minimal effective doses remain unknown .
There is a lack of valid data on the efficacy of interventions for the treatment of established pruritus | BACKGROUND AND OBJECTIVE Numerous drugs have been used to prevent or to treat opioid-induced pruritus in the surgical setting .
Their relative efficacy is not well understood . | We have studied the effect of propofol on the side effects associated with intrathecal morphine in 40 patients undergoing major arthroplasty . Patients received spinal anaesthesia with plain 0.5 % bupivacaine 20 mg mixed with preservative-free morphine 0.3 mg . Before injection of the local anaesthetic , the patients were allocated r and omly to receive either a bolus dose of propofol 10 mg followed by an infusion of 30 mg/24 h or equal volumes of 10 % Intralipid ( control group ) . The number of patients without postoperative nausea and vomiting ( PONV ) was similar in both groups . However , the incidence of nausea and vomiting was lower in the propofol ( 13 and 22 , respectively ) than in the control ( 34 and 36 ) group ( P < 0.01 and P < 0.05 , respectively ) . Severe vomiting episodes were less frequent in the propofol group ( 1 vs 11 ; P < 0.05 ) . Four patients in the propofol group and 12 patients in the control group had itching ( P < 0.05 ) . The incidence of urinary retention was similar in both groups . There was no additional sedation attributable to propofol . In conclusion , sub-hypnotic doses of propofol protected significantly against itching and had a modest effect on PONV after intrathecal morphine The purpose of this study was to determine whether subhypnotic doses of propofol effectively relieve pruritus in women who received intrathecal morphine for postoperative analgesia after cesarean delivery . Twenty-nine women who developed pruritus after undergoing an elective cesarean section and receiving intrathecal morphine ( 0.25 mg ) for postoperative analgesia were enrolled in this r and omized , prospect i ve , double-blind study . The women were r and omly assigned to receive either 1 mL of propofol ( n=17 ) or 1 mL of placebo ( n=12 ) IV . Pruritus was evaluated 5 min after treatment . In the absence of successful treatment , the women received another 1 mL of the same drug . Pruritus was again evaluated 5 min after the second dose . We found that pruritus was successfully treated twice in the propofol group and once in the placebo group ( P = not significant ) . The antipruritic action of propofol lasted for up to 6 h in one woman and 15 min in the other . The one success in the placebo group lasted for 15 min . We conclude that the success rate of propofol in treating pruritus in women who received intrathecal morphine for postoperative analgesia after cesarean delivery is not significantly different from that of placebo . Implication s : Pruritus is a common and bothersome side effect of neuraxial opioids after cesarean section . Subhypnotic doses of IV propofol ( 10 mg ) have been used to treat pruritus caused by neuraxial opioids . In this prospect i ve , r and omized , double-blind study , we found that propofol does not relieve pruritus in women who underwent cesarean section and received intrathecal morphine sulfate ( 0.25 mg ) for postoperative pain relief . ( Anesth Analg 1998;86:310 - 3 In order to evaluate the effect of preventive corticosteroid on the occurrence of pruritus after epidural anesthesia with morphine , we studied 95 patients undergoing cesarean section . Thirty-seven patients ( group I ) were given 20 mg of bupivacaine 0.5 % for the operation and 2 mg of morphine hydrochloride with 50 mg of Ultracortene-H immediately after the operation and 24 h later , and 58 patients ( group II ) were given epidural bupivacaine during the operation and epidural morphine hydrochloride immediately after the operation and 24 h later without Ultracortene-H. Only 8.1 % of group I patients had pruritus after the injection compared to 20.6 % in group II . We suggest that the addition of 50 mg Ultracortene-H to 2 mg epidural morphine analgesia after the operation might prevent severe forms of pruritus A majority of patients experience pruritus , nausea and /or emesis following epidural morphine administration post-cesarean section . Naloxone or diphenhydramine are commonly used to treat these side effects . Prevention or reduction in the incidence of side effects of epidural morphine is a clinical goal . The purpose of the study was to observe the efficacy of prophylactic administration of hydroxyzine on the incidence and severity of pruritus following the epidural administration of morphine in 40 patients who requested epidural morphine for postoperative pain relief . Group I ( n = 20 ) received saline , while Group II ( n = 20 ) received 50 mg of hydroxyzine ten minutes after the administration of 5 mg epidural morphine . Both solutions were administered by deep intramuscular injection in the thigh area . The results of this investigation demonstrated that hydroxyzine was efficacious in attenuating the incidence of severe pruritus Background and Objectives . Epidural morphine is accepted as an efficient means of postoperative pain management . However , development of side effects such as nausea and vomiting and pruritus has been reported . This study compared the efficacy of intravenous infusions of nalbuphine or naloxone in the prevention of epidural morphine‐related side effects . Methods . Seventy‐five female patients undergoing epidural anesthesia for total hysterectomy were enrolled in a r and omized , double‐blind study . At the end of the surgery , all patients received epidural 3 mg morphine ( every 12 hours ) for postoperative pain . Meanwhile , patients in group 1 received an adjuvant intravenous infusion of nalbuphine 60 μg/kg/h , patients in group 2 received intravenous infusion of naloxone 2 μg/kg/h , and patients in group 3 received intravenous saline infusion only . A rescue analgesic of intramuscular 50 mg meperidine ( every 4 hours ) was available for each patient . Patients were observed for 24 hours . Results . All patients had adequate postoperative pain relief . However , the proportion of patients requiring rescue analgesia and the total consumption of rescue analgesic were higher in group 2 than in the other two groups . The incidence of nausea and vomiting and pruritus was higher in group 3 than in the other two groups . Conclusions . We found that coadministration of either nalbuphine or naloxone with epidural morphine reduces the incidence of morphine‐related side effects . However , unlike naloxone , nalbuphine did not attenuate the analgesic effect of epidural morphine This study was design ed to evaluate the efficacy of nalmefene vs. naloxone in preventing side effects result ing from intrathecal opioids , in patients undergoing cesarean delivery . Eighty patients who were scheduled for elective cesarean delivery under spinal anesthesia were included in a double-blind , placebo-controlled study . Patients were r and omized into four groups : saline ; intravenous nalmefene 0.25 micro.kg(-1 ) every 12 h x 2 ; intravenous nalmefene 0.5 microg.kg(-1 ) every 12 h x 2 ; and naloxone infusion 48 microg.h(-1 ) ( 1.2 microg.ml(-1 ) ) . There were no significant differences among the groups with respect to pain , sedation , satisfaction , or the occurrence or treatment of pruritus or nausea . There was a significant difference among the groups with respect to the occurrence of vomiting ( P < 0.03 ) : both nalmefene groups had a higher rate of vomiting than did the control group ; the 0.25 microg.kg(-1 ) nalmefene group had a higher rate than did the naloxone group . The use of narcotic antagonists does not result in improved comfort in obstetrical patients receiving intrathecal morphine and fentanyl Background and Objectives Because the mechanism of inhibition of epidural morphine-induced pruritus by droperidol is not clear , this study was undertaken to determine the effects of larger doses of droperidol or morphine , or both . Methods A double-blind study was performed in 210 ASA I or II patients undergoing cesarean delivery , who were r and omly assigned to six groups . All patients received epidural anesthesia with 0.5 % bupivacaine containing 1:200,000 epinephrine , to which 2 mg ( groups 1 , 2 , and 3 ) or 4 mg ( groups 4 , 5 , and 6 ) morphine sulfate was added . Just after delivery , 2.5 mg droperidol was given intravenously to groups 2 and 5 , and 5 mg was given to groups 3 and 6 . During the postoperative period , the patients were assessed for the occurrence and severity of pruritus ( classified as absent , mild , moderate , or severe ) or other untoward symptoms . The groups were compared for the incidence of pruritus by the Mann-Whitney nonparametric test . Results The incidence of pruritus was significantly reduced only when the control group ( no droperidol ) was compared with the group that received 2.5 mg droperidol , both when 2 mg and when 4 mg morphine was used . A 5-mg dose of droperidol had no inhibitory effect . There was no difference in the incidence of pruritus between use of 2 mg and 4 mg morphine . Other untoward effects of morphine either could not be observed or occurred with an incidence unaffected by either dose of droperidol . Conclusion Pruritus caused by epidural use of 2 or 4 mg of morphine is inhibited by the intravenous use of 2.5 mg droperidol but not by a larger dose Propofol is associated with a low incidence of postoperative nausea and vomiting . In a prospect i ve , r and omized , double-blind , placebo-controlled study , we investigated the possible direct antiemetic properties of a subhypnotic dose of propofol . Fifty-two ASA physical status I or II patients , aged 15–60 yr with nausea and vomiting after minor gynecologic , orthopedic , or digestive tract surgery , were included in the study and received either propofol ( 10 mg = 1 mL ) or placebo ( 1 mL Intralipid ) intravenously in the postanesthesia care unit . Patients treated with propofol experienced a larger reduction in nausea and vomiting than patients treated with placebo ( 81 % vs 35 % success rate ; P < 0.05 ) . Patients successfully treated had a similar incidence of relapse ( propofol 28 % ; placebo 22 % ) within the first 30 min after therapy . Thirty-three percent of the propofol-treated patients and 44 % of the placebo-treated patients showed a minor increase in sedation . The level of postoperative pain did not change in either group . Hemodynamic values remained unchanged in both groups . Pain on injection ( 7.6 % ) or dizziness ( 3.6 % ) only occurred in the propofol group . We conclude that propofol has significant direct antiemetic properties The influence of two different concentrations of iv naloxone infusion on the analgesia and adverse effects of epidural morphine were compared in a double-blind , placebo-controlled study . Fortyfive patients undergoing gallbladder surgery were provided postoperative analgesia by 4 mg epidural morphine ; they then received an iv infusion over a 12-h period consisting of either 5 μg · kg−1 · h−1 naloxone , 10 μg · kg−1 · h−1 naloxone , or saline . Pain relief was assessed by hourly visual analog scoring ( VAS ) and by direct question ing of the patient . Requirement of additional analgesia was noted . Respiratory frequency was monitored every 15 min and arterial blood gases were analyzed every 2 h for 24 h. Peak expiratory flow ( PEF ) was recorded 6 and 24 h postoperatively . Steady-state kinetics of naloxone were determined by a modified radioimmunoassay ( RIA ) method . All patients had good to excellent postoperative pain relief . Naloxone , 5 μg · kg−1 · h−1 , did not appear to have any effect on epidural morphine analgesia . However , naloxone infusion at the rate of 10 μg.kg−1 h−1 reduced the duration of analgesia by about 25 % , and more frequent injections of epidural morphine were required to give effective analgesia . Complete reversal of analgesia was not seen in any patient . A dose-related stimulatory effect on respiratory frequency was noted in the groups receiving naloxone . Paco2 values also were better in these groups as compared to values in the placebo group . The steady-state plasma concentration of naloxone was 2.8–3.7 ng/ml during infusion at the rate of 5μg.kg−1 h−1 and 4.3–5.1 ng/ml during 10 μg · kg−1 h−1 naloxone infusion . The plasma clearance of naloxone was 30.5 and 35.4 ml . min−1 . kg−1 for the low and high dose groups , respectively , and showed a four-fold interindividual variation . The authors conclude that naloxone reverses epidural morphine analgesia in a dose-dependent manner . Low-dose naloxone infusion ( 5 μg.kg−1 h−1)prevents respiratory depression due to epidural morphine without affecting its analgesia OBJECTIVE To search for the optimal dosage of nalbuphine relief of intrathecal-morphine induced pruritus after caesarean section . METHODS Ninety parturients who developed moderate to severe pruritus caused by intrathecal morphine after caesarean section were r and omly allocated into 3 groups receiving 2 , 3 and 4 mg of intravenous nalbuphine respectively . The improvement of pruritus and adverse effects of nalbuphine such as increasing pain scores , nausea , vomiting , sedation and respiratory depression were evaluated at 15 minutes after nalbuphine administration . RESULTS Percentage of successful treatment of pruritus with 2 , 3 and 4 mg , nalbuphine were 86.7 , 96.7 and 100 , respectively ( p = 0.12 ) . There was no statistically significant difference in adverse effects . No evidence of respiratory depression was detected . However , there was significant increase in pain scores in group of 4 mg nalbuphine ( p = 0.004 ) . CONCLUSIONS Nalbuphine of 2 to 3 mg was considered to be adequate in treatment of intrathecal morphine induced pruritus after caesarean section without increasing pain scores or causing other side effects As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better evidence is published . But when is the evidence strong enough to justify changing a practice ? Individual studies that involve only small numbers of patients may have results that are distorted by the r and om play of chance and thus lead to less than optimal decisions . As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer . They use explicit methods and quality st and ards to reduce bias . Their results are the closest we can come to reaching the truth given our current state of knowledge . The questions about an intervention that a systematic review should answer are the following : 1 . Does it work ? 2 . If it works , how well does it work in general and compared with placebo , no treatment , or other interventions that are currently in use ? 3 . Is it safe ? 4 . Will it be safe and effective for my patients ? Whereas the critical appraisal and qualitative synthesis provided by review articles can be interpreted directly , the numerical products of quantitative review s can be more difficult to underst and and apply in daily clinical practice . This paper provides guidance on how to interpret the numerical and statistical results of systematic review s , translate these results into more underst and able terms , and apply them directly to individual patients . Many of these principles can also be used to interpret the numerical results of individual clinical studies . They are particularly relevant to systematic review s , however , because such review s contain more information than do primary studies and often exert greater influence than do individual studies . Making Sense of the Numerical Results of Clinical Studies Although the results of clinical studies can be expressed in intuitively meaningful ways , such results do not always easily translate into clinical decision making . For example , results are frequently expressed in terms of risk , which is an expression of the frequency of a given outcome . ( Risks are probabilities , which can vary between 0.0 and 1.0 . A probability of 0.0 means that the event will never happen , and a probability of 1.0 means that it always happens . ) Consider a hypothetical study of the recurrence of migraine headaches in a control group receiving placebo and a treatment group receiving a new antimigraine preparation , drug M ( a secondary prevention trial ) . Suppose that at the end of the trial , migraines recurred in 30 % of the control group ( the risk for recurrence was 0.30 ) but in only 5 % of the drug M group ( risk of 0.05 ) ( Table 1 ) . Table 1 . Numerical Expression of Hypothetical Clinical Trial Results The outcomes of the study are clear enough for the two groups when they are examined separately . But clinicians and patients are more interested in the comparative results , that is , the outcome in one group relative to the outcome in the other group . This overall ( comparative ) result can be expressed in various ways . For example , the relative risk , which is the risk in the treatment group relative to that in the control group , is simply the ratio of the risks in the two groups . In other words , relative risk is the risk in the treatment group divided by that in the control group , 0.05 0.30 , or 0.17 . The comparison can also be expressed as the reduction in relative risk , which is the ratio between the decrease in risk ( in the treatment group ) and the risk in the control group , 0.25 0.30 , or 0.83 ( Table 1 ) . ( The relative risk reduction can also be calculated as 1 relative risk ) . Although the clinical meaning of relative risk ( and relative risk reduction ) is reasonably clear , relative risk has the distinct disadvantage that a given value ( for example , 0.17 ) is the same whether the risk with treatment decreases from 0.80 to 0.14 , from 0.30 to 0.05 , from 0.001 to 0.00017 , and so forth . The clinical implication s of these changes clearly differ from one another enormously and depend on the specific disease and intervention . An important alternate expression of comparative results , therefore , is the absolute risk reduction . Absolute risk reduction is determined by subtracting the risk in one group from the risk in the other ( for example , the risk in the treatment group is subtracted from the risk in the placebo group ) . In the case of our migraine study , the absolute risk reduction would be 0.30 0.05 , which equals 0.25 , or 25 percentage points . In contrast , for a study in which the risk decreased from 0.001 to 0.00017 , the absolute risk reduction would be only 0.00083 , or 0.083 percentage points , which is a trivial change in comparison ( Table 1 ) . This arithmetic emphasizes the difficulty of expressing the results of clinical studies in meaningful ways . Relative risk and relative risk reduction clearly give a quantitative sense of the effects of an intervention in proportional terms but provide no clue about the size of an effect on an absolute scale . In contrast , although it tells less about proportional effects , absolute risk says a great deal about whether an effect is likely to be clinical ly meaningful . Despite this benefit , even absolute risk is problematic because it is a dimensionless , abstract number ; that is , it lacks a direct connection with the clinical situation in which the patient and physician exist . However , another way of expressing clinical research results can provide that clinical link : the number needed to treat ( NNT ) . Number Needed To Treat The NNT for a given therapy is simply the reciprocal of the absolute risk reduction for that treatment [ 1 , 2 ] . In the case of our hypothetical migraine study ( in which risk decreased from 0.30 without treatment with drug M to 0.05 with treatment with drug M , for a relative risk of 0.17 , a relative risk reduction of 0.83 , and an absolute risk reduction of 0.25 ) , the NNT would be 1 0.25 , or 4 . In concrete clinical terms , an NNT of 4 means that you would need to treat four patients with drug M to prevent migraine from recurring in one patient . To emphasize the difference between the concepts embodied in NNT and relative risk , recall the various situations mentioned above , in all of which the relative risk was 0.17 but in which the absolute risk decreased from 0.80 to 0.14 in one case and from 0.001 to 0.00017 in another . Note that the corresponding NNTs in these two other cases are 1.5 and 1204 , respectively : that is , you would need to treat 1.5 and 1204 patients to obtain a therapeutic result in these two situations compared with 4 patients with drug M ( Table 1 ) . The NNT can be calculated easily and kept as a single numerical reminder of the effectiveness ( or , as we will see , the potential for harm ) of a particular therapy . As we suggested , the NNT has the crucial advantage of direct applicability to clinical practice because it shows the effort that is required to achieve a particular therapeutic target . The NNT has the additional advantage that it can be applied to any beneficial outcome or any adverse event ( when it becomes the number needed to harm [ NNH ] ) . The concept of NNT always refers to a comparison group ( in which patients receive placebo , no treatment , or some other treatment ) , a particular treatment outcome , and a defined period of treatment . In other words , the NNT is the number of patients that you will need to treat with drug or treatment A to achieve an improvement in outcome compared with drug or treatment B for a treatment period of C weeks ( or other unit of time ) . To be fully specified , NNT and NNH must always specify the comparator , the therapeutic outcome , and the duration of treatment that is necessary to achieve the outcome . Important Qualities of the Number Needed To Treat The NNT is treatment specific . It describes the difference between treatment and control in achieving a particular clinical outcome . Table 2 shows NNTs from a selection of systematic review s and large r and omized , controlled trials . Table 2 . Numbers Needed To Treat from Systematic Review s and R and omized , Controlled Trials A very small NNT ( that is , one that approaches 1 ) means that a favorable outcome occurs in nearly every patient who receives the treatment and in few patients in a comparison group . Although NNTs close to 1 are theoretically possible , they are almost never found in practice . However , small NNTs do occur in some therapeutic trials , such as those comparing antibiotics with placebo in the eradication of Helicobacter pylori infection or those examining the use of insecticide for head lice ( Table 2 ) . An NNT of 2 or 3 indicates that a treatment is quite effective . In contrast , such prophylactic interventions as adding aspirin to streptokinase to reduce 5-week vascular mortality rates after myocardial infa rct ion may have NNTs as high as 20 to 40 and still be considered clinical ly effective . Limitations of the Number Needed To Treat Although NNTs are powerful instruments for interpreting clinical effects , they also have important limitations . First , an NNT is generally expressed as a single number , which is known as its point estimate . As with all experimental measurements , however , the true value of the NNT can be higher or lower than the point estimate determined through clinical studies . The 95 % CIs of the NNT are useful in this regard because they provide an indication that We have evaluated the efficacy of ondansetron in the prevention of opioid-induced pruritus in a prospect i ve , r and omized , double-blind , placebo-controlled study . Using a ' human model ' of opioid-induced pruritus , 80 ASA I-II patients about to undergo routine surgery were given either ondansetron 4 mg i.v . or 0.9 % saline i.v . ( 40 in each group ) , 30 min before alfentanil 10 mg kg-1 i.v . During the following 5 min , patients were observed for signs of perinasal scratching and at 5 min were asked about symptoms of pruritus . The study was then terminated and anaesthesia was induced . There was a significant reduction in the incidence of scratching in patients receiving ondansetron compared with placebo ( 42.5 % vs 70 % , respectively , P = 0.013 ) . The incidence of itching in the ondansetron group was less than that in the placebo group but this was not statistically significant ( 30 % vs 42.5 % , respectively , P = 0.245 ) . We conclude that the 5-HT3 antagonist ondansetron may have a role in the management of opioid-induced pruritus This study compared naloxone and nalbuphine when administered for treatment of side effects after epidural morphine , 5 mg , given for postcesarean analgesia . Patients requesting treatment for pruritus or nausea r and omly received , in a double-blind fashion , up to three intravenous doses of either naloxone 0.2 mg ( group 1 ; n = 20 ) or nalbuphine 5 mg ( group 2 ; n = 20 ) . The incidence of vomiting , the severity of nausea and pruritus , and the degree of sedation and pain were assessed before and 30 min after each dose . The first dose of nalbuphine decreased the incidence of vomiting ( P < 0.005 ) and the severity of nausea and pruritus ( P < 0.01 ) , whereas naloxone caused no significant changes . Sedation scores increased after nalbuphine ( P < 0.05 ) and remained unchanged after naloxone , whereas pain scores increased after naloxone ( P < 0.01 ) and were unchanged after nalbuphine . Eighteen patients in group 1 and 12 in group 2 received a second dose , and 8 and 4 patients , respectively , a third dose . Other than decreased pruritus after the second dose with both drugs , no further changes occurred . We conclude that nalbuphine is superior to naloxone for the treatment of side effects after epidural morphine . However , persistent symptoms may require supplemental therapy , as repeated doses proved less effective than the initial dose A r and omised , double-blind study was conducted to investigate the postoperative effects of subarachnoid morphine , with or without adrenaline , after major gynaecological surgery . Seventy-five women having spinal anaesthesia combined with either sedation or general anaesthesia were r and omised to receive subarachnoid morphine 0.25 mg with ( group MA ) or without ( group M ) adrenaline 200 ūg ; or normal saline ( group C ) . Groups M ( n=22 ) and MA ( n=25 ) differed significantly from control ( n=23 ) with respect to the quality and duration of postoperative analgesia ( P<0.0002 ) and to a higher incidence of pruritus ( P<0.02 ) . Groups were similar with respect to the incidence of other postoperative side-effects and respiratory data , although the latter showed a trend to less hypoxaemia in the control group . There was no significant difference in any outcome between groups MA and M. It was concluded that , under the study conditions in a post-gynaecological surgery population , the addition of adrenaline to subarachnoid morphine was of no benefit Background : Intrathecal sufentanil has been found to provide profound analgesia during labor . Epinephrine , when added to various local anesthetic agents or opioids , may modify the analgesic profile and incidence of side effects . The authors sought to determine the effect of adding 0.2 mg epinephrine to 10 µg sufentanil when administered for analgesia during labor . Methods : Forty women during active labor received 10 µg intrathecal sufentanil either with ( n = 20 ) or without ( n = 20 ) 0.2 mg epinephrine in a r and omized , blinded fashion . A combined spinal-epidural technique was used in which a 25-G Whitacre spinal needle was passed through a st and ard 17-G epidural needle . After injection of the study drug , an epidural catheter was passed , but no local anesthetics were given . Analgesia was quantitated using visual analog scores , as well as time elapsed until first request for additional analgesia via the epidural catheter ( 0.25 % bupivacaine ) . The incidence and severity of pruritus , nausea , and somnolence were assessed . Results : The duration ( median , range ) of analgesia was 90 ( 40 - 310 ) min in the plain sufentanil group ( SUF ) and 90 ( 45- 230 ) min in the sufentanil-epinephrine ( SUF-EPI ) group ( P = NS ) . The onset of analgesia was rapid ( within 5 min ) in both groups and visual analog scores did not differ at any observation point between groups . The incidence of pruritus was 80%16/20 ) in the SUF group , and 45 % ( 9/20 ) in the SUF-EPI group ( P = 0.05 ) . Four patients in the SUF group rated the pruritus as severe versus none in the SUF-EPI groups ( P = 0.05 ) . Seven patients ( 35 % ) in the SUF-EPI group experienced nausea , versus none in the SUF group ( P = 0.004 ) . No patient developed hypotension , motor blockade , fetal heart rate abnormalities , excessive sedation , or postdural puncture headache . Conclusions : Intrathecal sufentanil 10 µg , both with and without epinephrine , provided rapid-onset , albeit short- duration , analgesia during labor . Epinephrine did not prolong the duration of intrathecal sufentanil analgesia . The addition of epinephrine increased the incidence of nausea and decreased the incidence and severity of pruritus The effect of subhypnotic doses of propofol on intrathecal morphine‐induced pruritus was studied in a prospect i ve , r and omly allocated , double‐blind controlled trial . Fifty‐eight women undergoing elective lower segment Caesarean section for a singleton fetus received spinal anaesthesia with 2.5 ml hyperbaric 0.5 % bupivacaine and 0.2 mg of preservative‐free morphine . They then received propofol 1 ml ( 10 mg ) or Intralipid 1 ml ( control group ) intravenously after delivery . Pruritus was assessed using a five‐point verbal rating scale at hourly intervals for 8 h. A second dose of their allocated treatment drug was administered at the first recording of significant pruritus . The pruritus score was reassessed after 5 min and the treatment was repeated if pruritus remained . There were no differences between the groups in the onset of pruritus or its successful treatment . No adverse side‐effects were associated with this dose of propofol . There were no differences in the incidence of post‐operative nausea and vomiting between the two groups . Subhypnotic propofol is not an effective treatment for intrathecal morphine‐induced pruritus in women following Caesarean section To identify the opioid antagonist activity of nalmefene and to determine its duration in man , six healthy male subjects were pretreated on separate days with a saline placebo , 0.5 mg , 1 mg , or 2 mg nalmefene intravenously in a r and omized double-blind fashion . Opioid challenges with fentanyl , 2 μg/kg , then were administered 1,2,4,6 , and 8 h afterward . Respiratory depression was monitored by ventilatory and occlusion pressure responses during CO2 re-breathing , while analgesia to experimental pain was identified with the submaximal effort tourniquet ischemia test . One hour following placebo pretreatment , the initial fentanyl dose produced marked respiratory depression . Minute ventilation and occlusion pressure at a PCO2 60 mmHg during rebreathing ( VE60 and P0.160 ) were reduced to 29 and 41 % of control , respectively . The slopes of the ventilatory and occlusion pressure responses also decreased significantly to 51 and 55 % of control . Respiratory effects were similar with all subsequent fentanyl doses . Pretreatment with 2 mg nalmefene completely prevented the subjective and respiratory effects of fentanyl for the entire 8 h of the experiment . Nalmefene , 1 mg , significantly blunted the fentanyl effects for the same period , but VE60 values at 6 and 8 h were depressed significantly ( P < 0.05 ) to 66 and 61 % of control . The antagonist effects of the lowest nalmefene dose , 0.5 mg , persisted for about 4 h , at which time V E60 was 64 % of control . Fentanyl administration produced consistent increases in pain tolerance ( 44–55 % above control ) throughout the experiment . Nalmefene pretreatment abolished this analgesic response in a dose-related time course that mirrored the respiratory effects almost exactly . These findings demonstrate that nalmefene is an effective opioid antagonist with a duration of action far in excess of naloxone and more clearly related to dose The influence of two different doses of oral naltrexone on the adverse effects and the analgesia associated with intrathecal morphine was compared in a double-blind , placebo-controlled study . Thirty-five patients undergoing cesarean section were provided postoperative analgesia by 0.25 mg intrathecal morphine . Sixty minutes later they were given 6 mg naltrexone , 3 mg naltrexone , or placebo as an oral solution . Pain relief was assessed by the Visual Analog Scale . Requirements for additional analgesics and side effects were recorded . Duration of analgesia was shorter in the 3− and 6-mg naltrexone groups than in the placebo group , 10.0 ± 2.6 , 12.4 ± 2.6 , and 19.2 ± 4.5 h ( mean ± SEM ) , respectively , but values did not reach statistical significance . The incidence of pruritus and vomiting was significantly less in the 6-mg naltrexone group than in the other two groups ( P < 0.05 ) . Somnolence was significantly less in the 3− and 6-mg naltrexone groups than in the placebo group ( P < 0.05).Naltrexone ( 6 mg ) is an effective oral prophylactic against the pruritus and vomiting associated with intrathecal morphine for analgesia after cesarean section , but it is associated with shorter duration of analgesia There have been conflicting reports of the value of naloxone infusions to prevent the side-effects associated with epidural morphine . In our study , 29 patients undergoing thoracotomies for pulmonary surgery received epidural morphine ( 0.1 mg·kg1 ) shortly after induction of anaesthesia . One hour after arrival in the Recovery Room , one of four naloxone bolus and infusion sequences was administered : saline bolus followed by saline infusion ; 0.4 µg·kg1 naloxone bolus followed by 0.4 µg·kg-1·hr-1 naloxone infusion ; 2.0 µg·kg1 naloxone bolus followed by 2.0 µg·kg-1·hr-1 naloxone infusion ; and 4.0 µg·kg1 naloxone bolus followed by 4.0 µg·kg-1·hr-1 naloxone infusion . Although with the number of patients studied , there were no statistically significant differences among groups , clinical ly , there was a trend toward decreased analgesia with all three naloxone infusion doses as determined by analgesic requirements , longest analgesic-free period and visual analogue pain scores . In addition , side-effects occurred in all groups . We conclude that prophylactic naloxone , used in this manner , is not an appropriate technique for the prevention of side-effects associated with epidural morphine used for the prevention of pain after thoracotomy . RésuméUne controverse persiste au sujet de ľutilité du naloxone dans la prévention des effets secondaires associés à la morphine en injection épidurale . Nous avons étudié 29 patients ayant subis une thoracotomie pour chirurgie pulmonaire et qui ont reçus 0.1 mg·kg-1 de morphine en injection épidurale peu aprés ľinduction de ľanesthésie . Une heure après leur arrivée à la salle de réveil , on a administré une des quatres séquences suivantes ďun bolus de naloxone suivi ďune perfusion de naloxone : bolus de salin suivi ďune perfusion de salin ; bolus 0.4 µg·kg-1 de naloxone suivi ďune perfusion 0.4 µkg·hr-1 de naloxone ; bolus 2.0 µg·hr-1 de naloxone suivi ďune perfusion 2.0 µ·kg-1 · hr-1 de naloxone ; bolus 4.0 µ·kg-1 de naloxone suivi ďune perfusion 4.0 µ·kg1·hr-1 de naloxone . Dû au nombre restreint de patients étudiés , les résultats ne sont pas confirmés par analyse statistique . Mais defaçon clinique , le degré ďanalgésie a été diminué avec les trois doses de naloxone tel que déterminé par le besoin ďanalgésique supplémentaire , ďespace de temps maximum entre les doses ďanalgésie requises , et t’examen des analogues visuels de la douleur . Ľincidence des effets secondaires n’a pas été modifieé . Nous concluons done que les perfusions prophylatiques de naloxone , utilisées de cette façon , ne sont pas apropriées pour prévenir les effets secondaires de la morphine en injection épidurale pour soulager la douleur après une thoracotomie Epidural opioid analgesia can offer advantages over intravenous administration , however , opioid-related side effects are common after epidural administration . We studied the effect of adding nalbuphine ( NB ) , an opioid agonist-antagonist , to hydromorphone ( HM ) for patient-controlled epidural analgesia ( PCEA ) in 78 healthy women after elective cesarean delivery . Patients were r and omly assigned to one of four treatment groups . The control group received preservative-free HM ( Dilaudid [ R ] ) alone , 0.075 mg/mL , while the three study groups received HM , 0.075 mg/mL , containing preservative-free NB ( Nubain [ R ] ) 0.02 , 0.04 , or 0.08 mg/mL. Intraoperatively , all patients received epidural bupivacaine 0.5 % . Postoperatively , a patient-controlled anesthesia ( PCA ) device was connected to the epidural catheter and programmed to deliver a 3-mL loading dose of the analgesic solution . Subsequently , patients could self-administer 2 mL bolus doses on dem and with a 30-min lockout interval . Patients were encouraged to ambulate approximately 8 h after surgery , and PCEA therapy was discontinued when a clear liquid diet was tolerated . Visual analog scale scores were used to assess pain at 8-h intervals while using PCEA therapy . Although the overall incidences of nausea ( 19%-35 % ) and pruritus ( 32%-62 % ) were similar in all four groups , the addition of NB decreased the need for bladder catheterization . The highest NB concentration result ed in increased PCA dem and s during the 32-h study period . In conclusion , the combination of HM 0.075 mg/mL and NB 0.04 mg/mL result ed in lower nausea scores and a decreased incidence of urinary retention compared with HM alone , without increasing the opioid analgesic requirement . ( Anesth Analg 1997;84:757 - 63 Background : A naloxone infusion is effective in reducing epidural and intrathecal opioid‐related side effects . The use of naloxone infusion concomitant with intravenous morphine patient‐controlled analgesia ( PCA ) has not been evaluated , probably because of an expected direct antagonism of the systemic opioid effect . The authors compared the incidence of morphine‐related side effects and the quality of analgesia from two small doses of naloxone infusion . Methods : Sixty patients classified as American Society of Anesthesiologists physical status 1 , 2 , or 3 who were scheduled for total abdominal hysterectomies were enrolled in the study . Patients received a st and ardized general anesthetic . In the postanesthetic care unit , patients received morphine as a PCA . They were r and omized to receive either 0.25 micro gram [ center dot ] kg sup ‐1 [ center dot ] h sup ‐1 naloxone ( low dose ) , 1 micro gram [ center dot ] kg sup ‐1 [ center dot ] h sup ‐1 ( high dose ) , or saline ( placebo ) as a continuous infusion . Verbal rating scores for pain , nausea , vomiting , and pruritus ; sedation scores ; requests for antiemetic ; and morphine use were recorded for 24 h. Blood pressure , respiratory rate , and oxyhemoglobin saturation were also monitored . Results : Sixty patients completed the study . Both naloxone doses were equally effective in reducing the incidence of nausea , vomiting , and pruritus compared with placebo ( P < 0.05 by the chi‐squared test ) . There was no difference in the verbal rating scores for pain between the groups . The cumulative morphine use was the lowest in the low‐dose group ( 42.3 + /‐ 24.1 mg ; means + /‐ SD ) compared with the placebo ( 59.1 + /‐ 27.4 mg ) and high‐dose groups ( 64.7 + /‐ 33.0 mg ) at 24 h ( P < 0.05 by analysis of variance ) . There was no incidence of respiratory depression ( < 8 breaths/min ) and no difference in sedation scores , antiemetic use , respiratory rate , and hemodynamic parameters among the groups . Conclusions : Naloxone is effective in preventing PCA opioid‐related side effects . Naloxone infusion at 0.25 micro gram [ center dot ] kg sup ‐1 [ center dot ] h sup ‐1 not only attenuates these side effects but appears to reduce postoperative ( beyond 4–8 h ) opioid requirements . This dosing regimen can be prepared with 400 micro gram naloxone in 1,000 ml crystalloid given in 24 h to a patient weighing 70 kg We performed a prospect i ve , r and omized , double-blinded study in 60 postoperative pediatric patients aged 6 wk to 7 yr to compare the efficacy of butorphanol given epidurally or intravenously in preventing the side effects of epidural morphine . Three groups of patients received 60 micrograms/kg epidural morphine ; 20 patients also received epidural butorphanol 30 micrograms/kg , and 20 patients also received 30 micrograms/kg intravenous butorphanol . All patients were evaluated for analgesia , sedation , vomiting , urinary retention , pruritus , and respiratory depression for 24 h postoperatively . Although the overall incidence of side effects was not different in the three groups , the epidural butorphanol group had a significant decrease in severity of pruritus . Sedation was seen more frequently in the groups receiving butorphanol , but was most pronounced in the epidural butorphanol group . We conclude that butorphanol has little or no effect on the side effects of epidural morphine STUDY OBJECTIVE To determine whether the addition of butorphanol to epidural morphine is effective in reducing the frequency of side effects caused by neuraxial opioids . DESIGN R and omized , double-blind study . SETTING Large tertiary care pediatric hospital . PATIENTS 20 children between the ages of 2 and 17 years undergoing spinal , abdominal , or thoracic procedures . INTERVENTIONS Patients were divided r and omly into one of two groups to receive either 80 micrograms/kg of preservative-free epidural morphine ( Group 1 ) or 80 micrograms/kg of preservative-free epidural morphine with 40 micrograms/kg of butorphanol ( Group 2 ) . MEASUREMENTS AND MAIN RESULTS Blood pressure , heart rate , respiratory rate , and the first need for additional opioids were monitored in the two groups . In addition , pruritus , nausea and vomiting , and supplemental oxygen ( O2 ) required to maintain oxygen saturation ( SpO2 ) above 90 % were monitored . Children who received butorphanol in addition to epidural morphine were much less likely to develop pruritus or nausea and vomiting or to require supplemental O2 to maintain SpO2 above 90 % . CONCLUSION Butorphanol 40 micrograms/kg added to epidural morphine 80 micrograms/kg is effective in decreasing the occurrence of side effects caused by neuraxial opioids in pediatric patients BACKGROUND Opioid-related side effects associated with intravenous patient-controlled analgesia can be reduced by a low-dose naloxone infusion . The influence of nalmefene , a pure opioid antagonist with a longer duration of action , on opioid-related side effects has not been evaluated . This study was design ed to determine the dose-response relation for nalmefene for the prevention of morphine-related side effects in patients receiving intravenous patient-controlled analgesia . METHODS One hundred twenty women undergoing lower abdominal surgery were enrolled in the study . General anesthesia was induced using thiopental and rocuronium and maintained with desflurane , nitrous oxide , and fentanyl or sufentanil . All patients received neostigmine and glycopyrrolate to reverse residual neuromuscular blockade . No prophylactic antiemetics were administered . At the end of surgery , patients were r and omized to receive saline , 15 microg nalmefene , or 25 microg nalmefene intravenously . The need for antiemetic and antipruritic drugs and the total consumption of morphine during the 24-h study were recorded . The incidences of postoperative nausea , vomiting , pruritus , and pain were recorded 30 min after patients were admitted to the postanesthesia care unit . In addition , patient remembrance of these side effects was noted at 24 h after operation . RESULTS The need for antiemetic and antipruritic medications during the 24-h study period was significantly lower in the patients receiving nahmefene compared with those receiving placebo . However , the need to treat side effects was similar in the two nahmefene groups . Prophylactic administration of nalmefene reduced the patients remembrance of nausea and itching as assessed 24 h after operation . Although the total consumption of morphine during the 24-h study period was similar in the three groups , retrospectively patients who received nalmefene characterized their pain as less severe in the previous 24 h. CONCLUSION Compared with placebo , prophylactic administration of nalmefene significantly decreased the need for antiemetics and antipruritic medications in patients receiving intravenous patient-controlled analgesia with morphine In this prospect i ve r and omised study , pruritus and pain were evaluated in patients undergoing abdominal surgery in which intrathecal morphine was administered . Each patient received intrathecal morphine 0.3 mg prior to induction , followed by a st and ard anaesthetic . The patients were r and omly allocated to one of two groups . One group received 100 mg of rectal diclofenac immediately post‐induction . Patients receiving diclofenac had significantly lower pruritus scores at 30 min ( p = 0.0076 ) , 2 , 4 , 8 and 24 h postoperatively , as well as significantly reduced pain scores at each time point ( p < 0.0001 at each study interval ) . Morphine consumption in the first 24 h was also significantly lower in this group . In conclusion , rectal administration of diclofenac significantly reduces the incidence and severity of postoperative pruritus . It also significantly reduces pain and further analgesic requirements postoperatively BACKGROUND Spinally and epidurally administered morphine is frequently associated with pruritus . Isolated case reports indicate that ondansetron may be effective in this context . This study aims to investigate the effectiveness of ondansetron to treat this side effect . METHODS In a prospect i ve , r and omized , double-blind , placebo-controlled study , 100 patients with pruritus ( > 4 on a visual analog scale , on which 0 represents no pruritus and 10 represents worst pruritus imaginable ) after spinal or epidural administration of morphine , received either 8 mg ondansetron intravenously ( ondansetron group ) in 100 ml NaCl 0.9 % or vehicle ( placebo group ) . A decrease of more than 4 points on the visual analog scale 60 min after treatment was considered a success . Changes in levels of pain and sedation , hemodynamic values , and other side effects were checked regularly . The presence or absence of pruritus was assessed for the last time 24 h later . RESULTS The two groups were similar for demographic characteristics , the route of administration of morphine , and severity of pruritus at the beginning of the study . The ondansetron group showed a success rate of 70 % versus 30 % for the placebo group ( P > 0.05 ) . Among the successfully treated patients , three ( 9 % ) in the ondansetron group and six ( 40 % ) in the placebo group reported the recurrence of pruritus ( P < 0.05 ) . Among the successfully treated patients , none complained of residual pruritus 24 h later . No changes in pain or sedation levels were noted . Hemodynamic values remained stable , hemoglobin oxygen saturation did not decrease , and no other side effects were observed . CONCLUSION The administration of 8 mg ondansetron intravenously is an effective treatment for spinally or epidurally administered morphine-induced pruritus . In this clinical condition the treatment is safe and well tolerated Forty – Jive patients undergoing Caesarean section under epidural anaesthesia with bupivacaine were r and omly allocated to three groups . Group I received 4 mg of epidural morphine immediately postoperatively and 2 mg naloxone by intravenous infusion for 12 hours postoperatively ; group 2 was treated as group I but without naloxone infusion : group 3 received 10 mg morphine intramuscularly and 20 ml epidural saline after delivery of the baby . Epidural morphine 4 mg produced better postoperative analgesia than 10 mg of morphine intramuscularly ( p < 0·001 ) and the intravenous infusion of naloxone did not ablate the analgesic effects of epidural morphine . The incidence of itching and vomiting was higher in the epidural opioid groups ( p < 0.05 ) and intravenous naloxone , although it reduced the severity of the itching , did not reduce its overall incidence . Respiratory depression was not detected in any of the three groups This r and omized , double-blind study compared the efficacy of two mu-receptor antagonists , naloxone and nalbuphine , in the prophylactic management of pruritus in postcesarean section patients receiving epidural morphine . Dosages of study drugs were individualized by the use of a patient self-administration ( PSA ) device . All 51 patients were healthy women who received a uniform epidural anesthetic and epidural morphine ( 5 mg ) . Coded solutions were infused for 24 h , with 5-min PSA lockout times : Group A ( n = 17 ) , nalbuphine 2.5 mg/h , PSA nalbuphine 1 mg ; Group B ( n = 16 ) , naloxone 50 micro gram/h , PSA saline ; Group C ( n = 18 ) , naloxone 50 micro gram/h , PSA naloxone 40 micro gram . Patients were assessed for pruritus and pain every 8 h for 24 h. Both naloxone and nalbuphine provided good relief for pruritus ; median pain and pruritus scores were in the none-to-mild range ( 0 - 3 ) for all groups at all assessment intervals . The pruritus scores of the PSA saline group were higher during the 16- to 24-h period ( P < 0.05 ) than the scores of either group receiving mu-receptor antagonist by PSA . There was evidence of shortening of the duration of analgesia in patients receiving naloxone who required treatment for pruritus after 16 h. Patients who self-administered large doses of nalbuphine over the first 8 h also reported pain scores consistent with reversal of analgesia . The potency ratio for naloxone : nalbuphine for antagonism of the pruritic effects of epidural morphine was approximately 40:1 . Intervention to treat either unrelieved pruritus or pain , respectively , was necessary in the following numbers of patients : Group A , 0/1 ; Group B , 1/1 ; Group C , 2/2 . Prophylactic infusions offer the potential for labor cost savings by minimizing the need for episodic therapeutic interventions to treat pruritus . ( Anesth Analg 1996;82:641 - 7 Epidural morphine produces analgesia with a high incidence of side effects that include pruritus , nausea , and vomiting . This study investigated whether epidural or IV droperidol could alleviate these symptoms . In a prospect i ve , double-blind , r and omized , controlled trial , 97 pregnant women undergoing cesarean section were r and omly assigned to three groups . All received st and ard continuous epidural anesthesia . After delivery , each received 5 mg of epidural morphine with either no droperidol injection , 2.5 mg of epidural droperidol , or 2.5 mg of IV droperidol . The incidence , onset , duration , and severity of pruritus ; the onset and severity of pain ; and satisfaction were similar for each group , but the incidence and severity of nausea and vomiting was lower in the group that received IV droperidol ( P < 0.01 ) . Sedation was minimal throughout the study . Thus , epidural droperidol failed to alleviate the side effects caused by epidural morphine , but IV droperidol reduced both the incidence and severity of nausea and vomiting . These results suggest that droperidol acts systemically to counter the effects of epidural morphine but that it is not entirely effective . Implication s : A single dose of epidural morphine provides long-lasting pain relief for women who have undergone cesarean section , but it has some troublesome side effects ( itching , nausea , vomiting ) . We performed a prospect i ve , r and omized , controlled trial in 97 such women to study whether droperidol could reduce these side effects . We found that IV droperidol reduced nausea and vomiting but did not prevent itching , and that epidural droperidol failed to prevent all side effects . ( Anesth Analg 1998;86:532 - 7 In this prospect i ve , double-blind , r and omized study of women undergoing elective cesarean birth , the hypothesis that epidural butorphanol in various doses could effectively reduce or eliminate the side effects caused by epidural morphine was tested . Patients were r and omly assigned to one of four groups . All received a st and ard epidural anesthetic and 20 min after delivery each received 3 mg epidural morphine with either 1 mg butorphanol ( Group A ) , 2 mg butorphanol ( Group B ) , 3 mg butorphanol ( Group C ) , or 3 mL normal saline ( Group D ) . Patient evaluations were made preoperatively and 2 , 8 , and 24 h after delivery . These consisted of visual analog scores for pain , satisfaction , nausea , itch , and somnolence . At each evaluation , a CO2 challenge test , using portable equipment , was performed . Data from 71 patients were analyzed and all four groups were comparable in terms of age , height , weight , level of sensory block , and volume of local anesthetic used . There were no significant differences among groups in terms of pain , satisfaction , nausea , or pruritus . Groups A , B , and C had significantly higher somnolence scores at 8 h compared to Group D ( P < 0.001 ) . There were no significant differences among groups in CO2 challenge test data at any point during the study , but overall a reduced sensitivity to CO2 after opioid administration was observed across all groups . There were no clinical ly significant incidents of respiratory depression . Epidural butorphanol , in doses of 1 - 3 mg , failed to reduce the side effects from 3 mg epidural morphine given after cesarean birth . Patients who received epidural butorphanol reported significantly higher levels of somnolence Epidural morphine is effective in the treatment Of Postoperative pain , but the incidence of associated side effects is high . To assess a potential reduction of opioid side effects by droperidol , 4 mg morphine with either placebo or 2.5 mg droperidol was injected epidurally in a double-blind , r and omized , postoperative trial . Forty patients undergoing hip replacement surgery were studied . The overall incidence of side effects during the first 24 h in the group receiving droperidol and morphine was less than 50 % of that in the group receiving placebo and morphine ( P < 0.008 ) . Pruritus , emesis , nausea , urinary retention , and hypotension were diminished in the group with droperidol . No significant differences in duration or quality of analgesia were seen , Epidural injection of droperidol did not result in any local or systemic side effects A double-blind , placebo-controlled study of 60 patients post cesarean delivery was conducted to determine whether nalbuphine reverses the side effects of pruritus and respiratory depression associated with epidurally administered morphine . Patients r and omly received either three doses of intravenous nalbuphine or the equivalent volume of saline . Vital signs , sedation , pain , pruritus and oxygen saturation were assessed hourly for 18 hours . There were no statistically significant differences in demographic data , sedation level , pain scores or analgesia requirements . Only three patients had no pruritus , one who received nalbuphine and two who received saline . Five patients had respiratory depression ( respiratory rate lower than 10 BPM or oxygen saturation < 90 % ) ; three occurred in the nalbuphine group and two in the saline group . Although theoretically advantageous , nalbuphine , as administered in this study of obstetric patients , offered no prophylactic benefit against the pruritus associated with epidural morphine . Its benefit with regard to respiratory depression remains unclear Sixty patients , scheduled for Caesarean section were r and omly allocated to receive by the epidural route in a double‐blind fashion one of the following patient‐controlled analgesia mixtures for the relief of postoperative pain : sufentanil 2 μg.ml‐1 in 0.9 % sodium chloride , sufentanil 2 μg.ml‐1 + adrenaline 2.5 μg.ml‐1 , or sufentanil 2 μg.ml‐1 + clonidine 3 μg.ml‐1 . Patient‐controlled analgesia setting s were a basal infusion rate of 2.5 ml.h‐1 , an incremental dose of 2.5 ml , a lockout interval of 10 min and a 1‐h limit of 10 ml . Whereas patient demographics and pain scores between the groups were not different , the 24‐h consumption of sufentanil was significantly lower in the groups receiving a combination ( 167.5 SD 45 and 139.1 SD 31.9 μg for the adrenaline and clonidine groups respectively ) as compared to the plain sufentanil regimen ( 208.2 SD 38.9 μg ) . Although sufentanil requirements were the lowest in the clonidine admixture group , there were no differences with regard to sedation as compared to the plain sufentanil group . The quality of sleep appeared to be significantly better in the sufentanil/adrenaline group despite a significantly lower degree of sedation and higher incidence of pruritus . Treatment of pruritus with naloxone did not seem to influence the quality of analgesia Background : Postoperative nausea and vomiting ( PONV ) following major arthroplasty with spinal anaesthesia and intrathecal morphine is reported in 45–74 % of patients . This r and omised , double‐blind , placebo‐controlled trial was undertaken to determine whether a subhypnotic infusion of propofol has a prophylactic antiemetic effect in this patient population The influence of two different doses of oral naltrexone on the adverse effects and the analgesia of epidural morphine were compared in a double-blind , placebo-controlled study . Forty-five patients undergoing cesarean section were provided postoperative analgesia with 4 mg epidural morphine . Five minutes later they received 6 mg naltrexone , 9 mg naltrexone , or placebo as an oral solution . Pain relief was assessed by the Visual Analog Scale ( VAS ) and by direct question ing of the patients . Requirement for additional analgesics and side effects were noted . Respiratory effects of epidural morphine and naltrexone were assessed using the ventilatory responses to CO2 and by monitoring O2 saturation ( Spo2 ) using pulse oximetry . All patients in the placebo group had adequate analgesia . One of the 15 patients who received naltrexone 6 mg had inadequate analgesia versus five of the 15 patients who received naltrexone 9 mg ( P less than 0.05 ) , 9 mg versus placebo . Ten patients ( 67 % ) in the placebo group had pruritus while no patient in the 6 mg naltrexone group and one patient in the 9 mg group experienced mild pruritus ( P less than 0.05 ) , placebo versus other two groups . The CO2 response slopes were depressed compared to control values from 6 - 16 h in the placebo group , from 6 - 12 h in the 6 mg naltrexone group . No significant depression was noted in the 9 mg naltrexone group . The authors conclude that oral naltrexone 6 mg significantly reduces the incidence of pruritus associated with epidural morphine without affecting analgesia and that 9 mg naltrexone is associated with shorter duration of analgesia than 6 mg naltrexone Background and Objectives . Our objective was to study in more detail our previous finding that intravenous droperidol inhibits pruritus induced by epidural morphine . Methods . In a double blind study , 107 ASA I or II patients undergoing cesarean section received epidural anesthesia with 150 mg ( 30 ml ) of 0.5 % bupivacaine with 1:200,000 epinephrine and 2 mg of morphine hydrochloride in a single injection . They were r and omly allocated to either receive ( treated group , n = 54 ) or not receive ( control group , n = 53 ) an intravenous injection of 2.5 mg of droperidol just after delivery . During the postoperative period , the patients were assessed for the occurrence and severity of pruritus or other possible untoward symptoms . Pruritus was classified as absent , mild , moderate , or severe . Results . The incidence of pruritus in control group was absent , 26.4 % ; mild , 39.6 % ; moderate , 28.3 % ; severe , 5.7 % ; for the treated group , the incidences were , respectively : 59.2 ; 27.8 ; 13.0 ; and 0.0 % ( p = 0.0003 ; Mann-Whitney test ) . As for other side effects of morphine , nausea and vomiting had a similar incidence in the two groups ; urinary retention could not be analyzed because of bladder catheterization , and constipation , herpes labialis and clinical evidence of respiratory depression were never observed . Droperidol produced a greater incidence of somnolence ( 2 % in control and 17 % in treated group - p < 0.02 ; Fisher 's exact test ) , but it was never incapacitating . The incidence of hypotension was similar in the two groups . Conclusion . Intravenous droperidol reduces the incidence and severity of pruritus caused by epidural injection of morphine without inducing important side effects The effect of nalbuphine on the respiratory depression , pruritus and analgesia induced by epidural morphine was determined in a r and omized , prospect i ve , double-blind , placebo-controlled fashion . Twenty ASA physical status I women received 0.1 mg.kg-1 epidural morphine at induction of general anaesthesia for elective total abdominal hysterectomy . Group 1 ( n = 14 ) received 0.3 mg.kg-1 nalbuphine intravenously six hours after the epidural morphine administration . Group 2 ( n = 6 ) received saline . Prior to agent administration , six patients from the nalbuphine group and four patients from the saline group had respiratory depression indicated by a PaCO2 greater than 45 mmHg . After nalbuphine administration the PaCO2 ( mean + /- SE ) decreased from 49.5 + /- 1.2 mmHg to 42.5 + /- 0.7 mmHg ( p less than 0.005 ) while there was no significant change after saline administration . Nine of the 14 patients receiving nalbuphine appeared to become more se date d , despite an improvement in ventilation . Pruritus was antagonized by 0.1 mg.kg-1 nalbuphine ( p less than 0.006 ) . There was no reversal of analgesia after administration of 0.3 mg.kg-1 nalbuphine In this prospect i ve r and omised study , pruritus and pain were evaluated in patients undergoing abdominal surgery during which epidural fentanyl was administered . All patients had an epidural catheter inserted at the time of surgery . Epidural fentanyl 100 μg was administered intra‐operatively and infused at a concentration of 2 μgml−1 for 48 h postoperatively . All patients received a st and ard anaesthetic and , in addition , the study group had a 20 mg bolus of tenoxicam intravenously , intra‐operatively . Patients receiving tenoxicam demonstrated significantly lower pruritus and pain scores at 30 min , 2 , 4 , 8 and 24 h postoperatively as well as reduced pethidine requirements for breakthrough pain in the first 24 h. In conclusion , tenoxicam 20 mg significantly reduces the incidence and severity of postoperative pruritus in patients who received peri‐operative epidural fentanyl . In addition , it significantly reduces pain and further analgesic requirements postoperatively In a prospect i ve , r and omized , double-blind clinical trial , we compared the efficacy of propofol and naloxone for the treatment of spinal-morphine-induced pruritus . Forty patients presenting with severe pruritus within 24 h of epidural morphine administration were allocated to receive either propofol 10 mg intravenously ( i.v . ) or naloxone 2 micrograms/kg . In the absence of a positive response , a second dose of the same treatment was given 5 min later . Pruritus and the level of post-operative pain were assessed every 5 min up to the end of the study period ( 45 min ) using a verbal rating scale . The overall success rate in treating pruritus was similar in the two groups ( 80 % ) . The rate of success after the first injection of the treatment drug was also similar ( 55 % ) . The level of postoperative pain decreased after drug treatment in six patients ( 30 % ) in the propofol group versus none in the naloxone group ( P < 0.05 ) . Forty-five percent of the patients in the naloxone group had an increase in the level of postoperative pain versus none in the propofol group ( P < 0.05 ) . In conclusion , these results suggest that propofol and naloxone are equally effective in treating spinal-morphine-induced pruritus . However , the level of postoperative pain is significantly less in the propofol group OBJECTIVES To assess incidence and preventability of adverse drug events ( ADEs ) and potential ADEs . To analyze preventable events to develop prevention strategies . DESIGN Prospect i ve cohort study . PARTICIPANTS All 4031 adult admissions to a stratified r and om sample of 11 medical and surgical units in two tertiary care hospitals over a 6-month period . Units included two medical and three surgical intensive care units and four medical and two surgical general care units . MAIN OUTCOME MEASURES Adverse drug events and potential ADEs . METHODS Incidents were detected by stimulated self-report by nurses and pharmacists and by daily review of all charts by nurse investigators . Incidents were subsequently classified by two independent review ers as to whether they represented ADEs or potential ADEs and as to severity and preventability . RESULTS Over 6 months , 247 ADEs and 194 potential ADEs were identified . Extrapolated event rates were 6.5 ADEs and 5.5 potential ADEs per 100 nonobstetrical admissions , for mean numbers per hospital per year of approximately 1900 ADEs and 1600 potential ADEs . Of all ADEs , 1 % were fatal ( none preventable ) , 12 % life-threatening , 30 % serious , and 57 % significant . Twenty-eight percent were judged preventable . Of the life-threatening and serious ADEs , 42 % were preventable , compared with 18 % of significant ADEs . Errors result ing in preventable ADEs occurred most often at the stages of ordering ( 56 % ) and administration ( 34 % ) ; transcription ( 6 % ) and dispensing errors ( 4 % ) were less common . Errors were much more likely to be intercepted if the error occurred earlier in the process : 48 % at the ordering stage vs 0 % at the administration stage . CONCLUSION Adverse drug events were common and often preventable ; serious ADEs were more likely to be preventable . Most result ed from errors at the ordering stage , but many also occurred at the administration stage . Prevention strategies should target both stages of the drug delivery process Epidural morphine has been used more and more to provide long-lasting postoperative analgesia after cesarean delivery . However , the incidence of pruritus ( 20%-93 % ) and nausea ( 17%-60 % ) detract from the usefulness of epidural morphine . The purpose of this study was to evaluate , in 30 patients having epidural anesthesia for cesarean delivery , the analgesic efficacy and side effects when a combination of epidural morphine , a μ-receptor agonist , and butorphanol , a μ-receptor antagonist and κ-receptor agonist , was administered . After clamping of the umbilical cord , patients received 4 mg epidural morphine with 3 mL of normal saline ( group I ) , 4 mg epidural morphine with 1 mg butorphanol and 2 mL of normal saline ( group 2 ) , or 4 mg epidural morphine with 3 mg butorphanol ( group 3 ) . Patients were monitored for 24 h after administration of the study medications . There were no significant differences between the groups in visual analogue pain scores , time to first analgesic request , respiratory rate , or Trieger dot test performance in the 24 h immediately after these epidural injections . There were three patients in group 1 and one patient in group 2 who experienced oxygen saturations less than 90 % . ( No patients in group 3 developed an oxygen saturation less than 92 % . ) The patients in group 3 did not require treatment for pruritus or nausea , a response significantly different ( P < 0.001 and P < 0.05 , respectively ) from group 1 or group 2 . We conclude that 3 mg of butorphanol added to epidural morphine for postoperative analgesia after cesarean delivery decreases the occurrence of pruritus and nausea without significantly increasing respiratory depression or sedation , and without adversely affecting duration of analgesia |
13,591 | 18,780,583 | Findings to date suggest that BWE is an effective therapeutic tool .
People suffering from cognitive functioning deficits , stress , pain , headache/migraines , PMS , and behavioral problems benefited from BWE . | OBJECTIVE Brainwave entrainment ( BWE ) , which uses rhythmic stimuli to alter brainwave frequency and thus brain states , has been investigated and used since the late 1800s , yet many clinicians and scientists are unaware of its existence .
We aim to raise awareness and discuss its potential by presenting a systematic review of the literature from peer- review ed journals on the psychological effects of BWE . | Background 10 Hz electroencephalographic ( EEG ) alpha rhythms correlate with memory performance . Alpha and memory decline in older people . We wished to test if alpha-like EEG activity contributes to memory formation . Flicker can elicit alpha-like EEG activity . We tested if alpha-frequency flicker enhances memory in older people . Pariticpants aged 67–92 identified short words that followed 1 s of flicker at 9.0 Hz , 9.5 Hz , 10.0 Hz , 10.2 Hz , 10.5 Hz , 11.0 Hz , 11.5 Hz or 500 Hz . A few minutes later , we tested participants ' recognition of the words ( without flicker ) . Results Flicker frequencies close to 10 Hz ( 9.5–11.0 Hz ) facilitated the identification of the test words in older participants . The same flicker frequencies increased recognition of the words more than other frequencies ( 9.0 Hz , 11.5 Hz and 500 Hz ) , irrespective of age . Conclusion The frequency-specificity of flicker 's effects in our participants paralleled the power spectrum of EEG alpha in the general population . This indicates that alpha-like EEG activity may subserve memory processes . Flicker may be able to help memory problems in older people Pre‐operative anxiety is common and often significant . Ambulatory surgery challenges our pre‐operative goal of an anxiety‐free patient by requiring people to be ‘ street ready ’ within a brief period of time after surgery . Recently , it has been demonstrated that music can be used successfully to relieve patient anxiety before operations , and that audio embedded with tones that create binaural beats within the brain of the listener decreases subjective levels of anxiety in patients with chronic anxiety states . We measured anxiety with the State‐Trait Anxiety Inventory question naire and compared binaural beat audio ( Binaural Group ) with an identical soundtrack but without these added tones ( Audio Group ) and with a third group who received no specific intervention ( No Intervention Group ) . Mean [ 95 % confidence intervals ] decreases in anxiety scores were 26.3%[19–33 % ] in the Binaural Group ( p = 0.001 vs. Audio Group , p < 0.0001 vs. No Intervention Group ) , 11.1%[6–16 % ] in the Audio Group ( p = 0.15 vs. No Intervention Group ) and 3.8%[0–7 % ] in the No Intervention Group . Binaural beat audio has the potential to decrease acute pre‐operative anxiety significantly Users of a commercial light therapy device who were using it to treat migraine were surveyed prospect ively to determine what results they obtained after 30 days of daily use . Out of a total of 55 migraineurs , 44 % reported that the frequency of their migraine attacks after the treatment was ' Somewhat Less ' or ' Much Less ' ( under a conservative interpretation of these categories ) . Considering only the 28 migraineurs who stated that their migraine attacks were normally preceded by warning signs , 53 % reported that the frequency of their migraine attacks was ' Somewhat Less ' or ' Much Less ' . In view of the limited efficacy and undesirable side-effects of the available migraine preventive drugs , photic stimulation ( flickering light therapy ) must be considered a possible preventive treatment for migraine INTRODUCTION Binaural beat technology ( BBT ) products are sold internationally as personal development and health improvement tools . Producers suggest benefit from regular listening to binaural beats including reduced stress and anxiety , and increased focus , concentration , motivation , confidence , and depth in meditation . Binaural beats are auditory brainstem responses that originate in the superior olivary nucleus as a result of different frequency auditory stimuli provided to each ear . Listeners to binaural beat " hear " a beat at a frequency equal to the difference between the frequencies of the applied tones . OBJECTIVES The objectives of this pilot study were to gather preliminary data on psychologic and physiologic effects of 60 days daily use of BBT for hypothesis generation and to assess compliance , feasibility , and safety for future studies . DESIGN Uncontrolled pilot study . SUBJECTS Eight healthy adults participated in the study . INTERVENTION Participants listened to a CD with delta ( 0 - 4 Hz ) binaural beat frequencies daily for 60 days . OUTCOME MEASURES Psychologic and physiological data were collected before and after a 60-day intervention . PSYCHOLOGIC : Depression ( Beck Depression Inventory-2 ) , anxiety ( State-Trait Anxiety Inventory ) , mood ( Profile of Mood States ) , absorption ( Tellegen Absorption Scale ) and quality of Life ( World Health Organization- Quality of Life Inventory ) . PHYSIOLOGICAL : Cortisol , dehydroepi and rosterone , melatonin , insulin-like growth factor-1 , serotonin , dopamine , epinephrine , norepinephrine , weight , blood pressure , high sensitivity C-reactive protein . RESULTS There was a decrease in trait anxiety ( p = 0.004 ) , an increase in quality of life ( p = 0.03 ) , and a decrease in insulin-like growth factor-1 ( p = 0.01 ) and dopamine ( p = 0.02 ) observed between pre- and postintervention measurements . CONCLUSIONS Binaural beat technology may exhibit positive effect on self-reported psychologic measures , especially anxiety . Further research is warranted to explore the effects on anxiety using a larger , r and omized and controlled trial OBJECTIVES This report presents both age-adjusted and unadjusted statistics from the 2002 National Health Interview Survey on selected health measures for children under 18 years of age , classified by sex , age , race , Hispanic origin , family structure , parent 's education , family income , poverty status , health insurance coverage , place of residence , region , and current health status . The topics covered are asthma , allergies , learning disability , Attention Deficit Hyperactivity Disorder ( ADHD ) , use of prescription medication , respondent-assessed health status , school-loss days , usual place of health care , time since last contact with a health care professional , unmet dental needs , time since last dental contact , and selected measures of health care access . SOURCE OF DATA The NHIS is a multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention 's National Center for Health Statistics and is representative of the civilian noninstitutionalized population of the United States . Data are collected during face-to-face interviews with adults present at the time of interview . Information about children is collected for one r and omly selected child per family in face-to-face interviews with an adult proxy respondent familiar with the child 's health . SELECTED HIGHLIGHTS In 2002 , most U.S. children under 18 years of age had excellent or very good health ( 84 % ) . However , 10 % of children had no health insurance coverage , and 5 % of children had no usual place of health care . Twelve percent of children had ever been diagnosed with asthma . An estimated 8 % of children 3 - 17 years of age had a learning disability , and an estimated 7 % of children had ADHD In an open study 17 women with confirmed , severe and long-st and ing premenstrual syndrome used photic stimulation with a flickering red light , every day for up to four menstrual cycles . At the end of treatment prospect ively recorded median luteal symptom scores were reduced by 76 % ( 95 % confidence interval 54 - 93 , P < 0.001 ) , with clinical ly and statistically significant reductions for depression , anxiety , affective lability , irritability , poor concentration , fatigue , food cravings , bloating and breast pain . Twelve of the 17 patients ( 71 % ) no longer had the premenstrual syndrome . One patient failed to improve . One patient withdrew because of worsening premenstrual depression , but photic stimulation was otherwise well tolerated . The improvement is greater than that reported for relaxation or in open studies of fluoxetine , and much more than historical placebo rates . Photic stimulation may be a useful treatment for the premenstrual syndrome , and by its suggested action on circadian rhythms may have wider therapeutic applications Stress and burnout are widely acknowledged as major causes of societal and individual problems in the Western world . In order to reduce material and i m material expenses , increased efforts are made to enhance relaxation and stress reduction . Based on neuropsychological findings , alternative ways have been explored , one of them being the application of so-called brain wave synchronizers , which are said to induce a relaxation response by entraining alpha brain-wave activity ( 8–13 Hz ) through audiovisual stimulation . A double blind , quasi-experiment was conducted among employees at a Dutch addiction care center to investigate the possible effects of two distinct brainmachine programs on burnout and anxiety . Subjects in both conditions showed a significant , immediate decrease in state anxiety as assessed by Spielberger 's State-Trait Anxiety Inventory ( STAI ) and reported a range of subjective effects . However , a long-term effect on burnout , as measured with Maslach 's Burnout Inventory ( MBI-NL ) , could not be established . A long-term effect on anxiety ( STAI ) , as investigated by interrupted time-series measurement , could not be established either . These and other findings suggest that the major cl aims with respect to these machines can not hold over time , although pleasant short-term effects do occur . Individual differences in baseline responsivity , the stable character of burnout dimensions , or the ill-defined nature of relaxation , or a combination of these , may account for these results OBJECTIVES When two auditory stimuli of different frequency are presented to each ear , binaural beats are perceived by the listener . The binaural beat frequency is equal to the difference between the frequencies applied to each ear . Our primary objective was to assess whether steady-state entrainment of electroencephalographic activity to the binaural beat occurs when exposed to a specific binaural beat frequency as has been hypothesized . Our secondary objective was to gather preliminary data on neuropsychologic and physiologic effects of binaural beat technology . DESIGN A r and omized , blinded , placebo-controlled crossover experiment in 4 healthy adult subjects . INTERVENTION Subjects were r and omized to experimental auditory stimulus of 30 minutes of binaural beat at 7 Hz ( carrier frequencies : 133 Hz L ; 140 Hz R ) with an overlay of pink noise resembling the sound of rain on one session and control stimuli of the same overlay without the binaural beat carrier frequencies on the other session . OUTCOME MEASURES Data were collected during two separate sessions 1 week apart . Neuropsychologic and blood pressure data were collected before and after the intervention ; electroencephalographic data were collected before , during , and after listening to either binaural beats or control . Neuropsychologic measures included State Trait Anxiety Inventory , Profile of Mood States , Rey Auditory Verbal List Test , Stroop Test , and Controlled Oral Word Association Test . Spectral and coherence analysis was performed on the electroencephalogram ( EEG ) , and all measures were analyzed for changes between sessions with and without binaural beat stimuli . RESULTS There were no significant differences between the experimental and control conditions in any of the EEG measures . There was an increase of the Profile of Mood States depression subscale in the experimental condition relative to the control condition ( p = 0.02 ) . There was also a significant decrease in immediate verbal memory recall ( p = 0.03 ) in the experimental condition compared to control condition . CONCLUSIONS We did not find support for steady-state entrainment of the scalp-recorded EEG while listening to 7-Hz binaural beats . Although our data indicated increased depression and poorer immediate recall after listening to binaural beats , larger studies are needed to confirm these findings OBJECTIVES This report presents both age-adjusted and unadjusted statistics from the 2005 National Health Interview Survey ( NHIS ) on selected health measures for children under 18 years of age , classified by sex , age , race , Hispanic origin , family structure , parent education , family income , poverty status , health insurance coverage , place of residence , region , and current health status . The topics covered are asthma , allergies , learning disability , Attention Deficit Hyperactivity Disorder ( ADHD ) , prescription medication use , respondent-assessed health status , school-loss days , usual place of health care , time since last contact with a health care professional , selected measures of health care access and utilization , and dental care . SOURCE OF DATA NHIS is a multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention 's National Center for Health Statistics and is representative of the civilian noninstitutionalized population of the United States . Data are collected for all family members during face-to-face interviews with adults present at the time of interview . Additional information about children is collected for one r and omly selected child per family in face-to-face interviews with an adult proxy respondent familiar with the child 's health . SELECTED HIGHLIGHTS In 2005 , most U.S. children under 18 years of age had excellent or very good health ( 82 % ) . However , 9 % of children had no health insurance coverage , and 5 % of children had no usual place of health care . Thirteen percent of children had ever been diagnosed with asthma . An estimated 7 % of children 3 - 17 years of age had a diagnosed learning disability , and an estimated 7 % of children had ADHD The effects of a brain wave synchronizer ( BWS ) on endodontic ( root canal ) anxiety was evaluated in the clinical practice s of the senior author . The experimental groups were : ( 1 ) a verbal method ( routine calming words by dentist ) plus BWS ( N = 10 ) and ( 2 ) verbal method plus BWS and alpha relaxation tape ( N = 10 ) . The control group was verbal method alone ( N = 10 ) . All three groups were evaluated during a complete endodontic treatment by the use of galvanic skin resistance ( GSR ) , pulse rate ( PR ) , physical responses , and pre- and post-treatment question naires . Recordings were made during the following periods : ( 1 ) start ; ( 2 ) local anesthetic injection ; ( 3 ) rubber dam application ; ( 4 ) drilling ; ( 5 ) x-ray taking ; ( 6 ) instrumentation ; ( 7 ) obturation ; and ( 8) conclusion . Results showed that the experimental groups were significantly better than the control group in the reduction of endodontic anxiety . The findings reinforced the belief that local anesthetic injection is the most anxiety producing aspect of endodontic treatment |
13,592 | 25,887,100 | VTE history was found as a VTE risk factor of THA but an controversial factor of TKA .
Cemented fixation as compared to cementless fixation was found as a risk factor for VTE only of TKA .
TKA surgery itself was confirmed as a VTE risk factor compared with THA surgery .
Conclusions This systematic review of high level evidence s published in recent ten years identified a range of potential factors associated with VTE risk of total joint arthroplasty . | Background Risk factors for venous thromboembolism ( VTE ) of total joint arthroplasty ( TJA ) have been examined by many studies .
A comprehensive systematic review of recent findings of high evidence level in this topic is needed . | Venous thromboembolic disease remains the most common reason for readmission after total hip arthroplasty . Prospect i ve analysis of screening contrast venography was done from 1984 to 2003 in 1972 patients having elective total hip arthroplasty . Patients with deep venous thrombosis or pulmonary embolism received warfarin therapy ; those with negative venograms received no further anticoagulation . From 1984 to 1992 , patients not completing venography were discharged without warfarin ; since 1993 , patients without venography received warfarin for 6 weeks . Readmission for deep venous thrombosis , pulmonary embolism , or bleeding was tracked for 6 months . Venograms were completed in 1032 patients ; 175 ( 16.9 % ) had deep venous thrombosis . Deep venous thrombosis was reduced by a clinical pathway that included continuous epidural anesthesia ( 14.2 % versus 22.5 % ) . The overall readmission rate for venous thromboembolic disease was 1.62 % , including 14 pulmonary emboli ( three fatal ) and 18 femoral deep venous thrombosis . Readmission occurred in 0.27 % ( 1 of 360 ) patients on continued warfarin , compared with 2.2 % ( 19 of 880 ) with negative venograms discharged without further anticoagulation . Three patients ( 0.15 % ) suffered fatal pulmonary emboli ; all had negative venograms and received no outpatient prophylaxis . Extended outpatient warfarin therapy provided effective protection against venous thromboembolic disease readmission . Surveillance venography was a poor predictor of need for continued prophylaxis ; all patients should have extended anticoagulation after total hip arthroplasty . Level of Evidence : Therapeutic study , Level I-1 ( high- quality r and omized trial with statistically significant difference or no statistically significant difference but narrow confidence intervals ) . See the Guidelines for Authors for a complete description of levels of evidence There are many reports concerning the aetiology and prophylaxis of deep-vein thrombosis ( DVT ) but little is known about its natural history . The purpose of our study was to identify the incidence and site of DVT , the risk factors for pulmonary embolism and the natural history of DVT after total hip replacement ( THR ) in patients who do not receive any form of prophylactic or therapeutic treatment for DVT . Two hundred patients who had a primary THR were included : 100 had one-staged bilateral THR and 100 had unilateral THR and 150 implants were cemented and 150 cementless . Coagulation assays , a full blood count , blood typing and serum chemical profile tests were performed for all patients on three separate occasions . Bilateral simultaneous or unilateral venograms were performed on the sixth or seventh postoperative day and perfusion lung scans preoperatively and on the seventh or eighth postoperative day . Further venograms were performed in all patients who had thrombi six months later . In the patients with bilateral THR , 52 ( 26 % ) venograms were positive for thrombi , while in the patients with unilateral THR 20 ( 20 % ) were positive ( p = 0.89 ) . In the patients with a cemented THR , 31 venograms ( 20.7 % ) were positive for thrombi , while in those with a cementless THR 41 ( 27.3 % ) were positive ( p = 0.654 ) . Further venograms in all 72 patients who had thrombi at six months after operation showed that they resolved completely and spontaneously regardless of their site and size . No patients had symptoms of pulmonary emboli and none were seen on the perfusion lung scans . Two patients died from unrelated causes . Although the prevailing opinion is that patients with proximal venous thrombosis should be treated with anticoagulants , our study has shown that all thrombi regardless of their site and size resolve spontaneously without associated pulmonary embolism Intraoperative pulmonary embolism occurs not only during cemented but also during cementless total hip arthroplasty ( THA ) . We determined whether the ROBODOC femoral milling system can reduce intraoperative pulmonary embolism , by using of transesophageal echocardiography and hemo-dynamic monitoring . We did a prospect i ve clinical trial with 71 patients ( 75 hips ) who were divided into 2 groups : group 1 , 46 patients ( 50 hips ) who underwent cementless THA with preparation of the femoral canal using ROBODOC ; group 2 , 25 patients ( 25 hips ) who underwent conventional cementless THA surgery in whom separate measurements were made during preparation of the femur , insertion of the stem and relocation of the hip . The incidence of severe embolic events was lower in group 1 than in group 2 . Our findings suggest that the ROBODOC femoral milling system may reduce the risk of clinical ly significant pulmonary embolism during cementless Introduction This prospect i ve study was design ed to confirm risk factors and to assess the incidence of deep vein thrombosis after total hip and surface replacement arthroplasty in Korean patients not receiving anticoagulation prophylaxis and to determine efficacy of plasma D-dimer levels as a screening test . Material s and methods From May 2003 to August 2004 , 221 consecutive patients undergoing unilateral total hip arthroplasty and hip resurfacing were evaluated . All patients underwent ultrasonography preoperatively and venography and /or ultrasonography on postoperative day 7 . Plasma D-dimer levels were estimated by latex immuno-assay preoperatively and on days 3 and 7 postoperatively . Results Of the 221 patients in our cohort , 23 developed deep vein thrombosis ( 10.4 % ) . Age ( r = 0.245 , P < 0.001 ) and gender ( r = 0.155 , P = 0.021 ) significantly correlated with deep vein thrombosis . Rise in incidence paralleled increase in age ( X2 = 32.860 , P < 0.001 ) . D-dimer levels on postoperative days 3 ( γ = 0.364 , P < 0.001 ) and 7 ( γ = 0.470 , P < 0.001 ) were significantly correlated to the development of DVT . Conclusion While incidence of deep vein thrombosis in Korean population after THA was lower than that in the West ; it increased with age , and in female gender . Significant correlation was found between D-dimer levels and the development of deep vein thrombosis Introduction : The incidence of venous thromboembolism ( VTE ) in Western population s undergoing major orthopaedic surgery without any thromboprophylaxis has been reported to range from 32 % to 88 % . There is however limited information on incidence of VTE in Indian patients and most of the Indian patients undergoing these surgeries do not receive any form of prophylaxis regardless of their risk profile . Methods : A prospect i ve study was performed on 147 patients undergoing major orthopaedic surgery for total knee replacement ( TKR ) , total hip replacement ( THR ) , and proximal femur fracture fixation ( PFF ) without any prophylaxis . These patients were profiled for presence of the known risk factors responsible for development of VTE . A duplex ultrasound on both lower limbs was done 6 to 10 days after surgery . Twenty three patients underwent THR , 22 patients underwent TKR , and 102 underwent surgery for PFF . The patients were assessed clinical ly for any signs of deep venous thrombosis ( DVT ) and pulmonary embolism ( PE ) . A helical CT scan was done in case of suspicion of PE and a duplex ultrasound was done in case of clinical suspicion of DVT irrespective of the stage of study . Results : The overall incidence of VTE was 6.12 % and that of PE was 0.6 % . The risk factors that were found to be significantly responsible for development of VTE ( p < 0.05 ) were : immobility greater than 72 hours , malignancy , obesity , surgery lasting more than two hours . Conclusion : The study reconfirms the belief that DVT has a lower incidence in Indian patients as compared with other ethnic groups BACKGROUND In view of recent substantial changes in the management of orthopedic surgery patients , a study was performed in order to up date data on the epidemiology of venous thromboembolism ( VTE ) in patients undergoing lower limb arthroplasty according to contemporary practise . METHODS We performed a prospect i ve observational study of a cohort of consecutive patients hospitalized for total hip or knee replacement in June 2003 . The primary study outcome was the incidence of symptomatic VTE at 3 months . All events were adjudicated by an independent critical event committee . RESULTS Data from 1080 patients ( mean age 68.0 years ) were available ; 63.2 % were undergoing total hip replacement and 36.8 % total knee replacement . Pharmacological thromboprophylaxis was administered for a mean time of 36 days . Injectable antithrombotics were used in more than 99 % of patients , irrespective of the type of surgery . The incidence of the primary study outcome was 1.8 % ( 20 events ; 95 % CI : 1.0 - 2.6 % ) . The incidences were 1.3 % and 2.8 % in hip and knee surgery patients , respectively . There were two pulmonary embolisms , both in knee surgery patients ; neither was fatal . Thirty-five per cent of VTEs occurred after hospital discharge . An age of at least 75 years and the absence of ambulation before hospital discharge were the only significant ( P < 0.05 ) predictors of VTE . The rate of clinical ly significant bleeding was 1.0 % and the rate of death was 0.9 % . CONCLUSIONS The incidence of symptomatic VTE after lower limb arthroplasty is low , even if there is still a need to improve thromboprophylaxis , notably in patients undergoing knee arthroplasty Background Heparin-induced thrombocytopenia ( HIT ) is a thromboembolic complication that can occur with unfractionated heparin ( UFH ) or low molecular weight heparin ( LMWH ) . Our objective was to determine and compare the incidence of IgG-class HIT antibodies in patients undergoing total hip arthroplasty ( THA ) or total knee arthroplasty ( TKA ) with different antithrombotic prophylaxis therapies and their contributions to the occurrence of venous thromboembolism ( VTE ) . Methods A prospect i ve observational study was performed for 374 Japanese patients undergoing THA or TKA to determine the incidence of VTE . IgG-class anti-PF4/heparin antibodies were measured using IgG-specific EIA before and after the operation . Results In the clinical outcome , the incidence of symptomatic deep vein thrombosis ( DVT ) was 15.0 % ( 56/374 , TKA ; 35 , THA ; 21 ) and pulmonary emboli ( PE ) were not observed . The total seroconversion incidence of IgG-class PF4/heparin antibodies was 19.8 % ( 74/374 ) . The seroconversion incidence of IgG-class PF4/heparin antibodies was higher in patients receiving UFH ( 32.7 % ) compared to those receiving LMWH ( 9.5 % ) or fondaparinux ( 14.8 % ) . Furthermore , the seroconversion incidence was significantly higher in patients undergoing TKA compared to those undergoing THA . Based on multivariate analysis , seroconversion of the IgG-class PF4/heparin antibodies was independent a risk factor for symptomatic DVT . Conclusion Our findings show that the seroconversion of IgG-class anti-PF4/heparin antibodies differed with various anti-thrombotic prophylaxis therapeutics and was associated with the risk of DVT in a subset of patients undergoing total joint arthroplasty ( TKA and THA ) Venous thromboembolism ( VTE ) is an important complication of major orthopaedic surgery of the lower limbs . Fondaparinux , a synthetic pentasaccharide and highly selective inhibitor of activated Factor Xa , is the first in a new class of antithrombotic agents . To determine the optimal dose in Japanese patients , double-blind , placebo-controlled , dose-ranging studies of fondaparinux were conducted in patients undergoing total knee replacement ( TKR ) or total hip replacement ( THR ) surgery . Patients were r and omly assigned to receive a once-daily subcutaneous injection of fondaparinux ( 0.75 , 1.5 , 2.5 , or 3.0 mg ) or placebo in Study 1 ( TKR ) and Study 2 ( THR ) . In Study 1 , the incidence of VTE was 65.3 % in the placebo group and was 34.2 % , 21.3 % , 16.2 % , and 9.5 % in the groups receiving 0.75 , 1.5 , 2.5 , and 3.0 mg fondaparinux respectively . In Study 2 , the incidence of VTE was 33.8 % in the placebo group and was 24.2 % , 4.6 % , 7.4 % , and 14.4 % in the 0.75 , 1.5 , 2.5 , and 3.0 mg fondaparinux groups respectively . Dose – response effects were observed in both studies ; however , no statistically significant differences in major bleeding events were found among any groups . Fondaparinux proved to be a potent anticoagulant with a favourable benefit-to-risk ratio in the prevention of VTE in these study patients .RésuméLes complications thromboemboliques sont nombreuses dans la plupart des interventions de chirurgie orthopédique au niveau des membres inférieurs . Le fondaparinux ( pentas saccharide synthétique ) est un élément important parmi tous les agents anti-thrombotiques . De façon à déterminer la dose optimale de ce produit , une étude en double aveugle avec placebo a été conduite chez des patients devant bénéficier d’une prothèse totale du genou ou d’une prothèse totale de hanche . Les patients ont été r and omisés de façon à recevoir une fois par jour une injection sous cutanée de fondaparinux ( 0.75 , 1.5 , 2.5 , ou 3 mg ) ou de placebo . L’incidence de la thrombose veineuse a été de 65.3 % dans le groupe placebo et de 34.2 % , 21.3 % , 16.2 % et 9.5 % dans les groupes recevant respectivement 0.75 , 1.5 , 2.5 et 3 mg de fondaparinux , pour le groupe prothèse du genou . Pour le groupe prothèse de hanche l’incidence des complications thromboemboliques a été de 33.8 % dans le groupe placebo et a été respectivement de 24.2 % , 4.6 % , 7.4 % et 14.4 % dans les groupes ayant reçu 0.75 , 1.5 , 2.5 et 3 mg de fondaparinux . Il n’y a pas de différence significatives en terme de saignement , dans chaque groupe . le fondaparinux est un anti-coagulant actif avec un bénéfice/risque important dans la prévention des thromboses veineuses et des accidents thromboemboliques dans cette étude de patients BACKGROUND Anticoagulant prophylaxis substantially reduces the risk of venous thromboembolism ( VTE ) after major orthopedic surgery . The direct factor Xa inhibitor YM150 is currently under investigation for the prevention of VTE , stroke and ischemic vascular events in patients after orthopedic surgery , with atrial fibrillation and with acute coronary syndrome , respectively . OBJECTIVES To investigate the efficacy and safety of YM150 for the prevention of VTE following elective total hip arthroplasty . PATIENTS / METHODS Patients were r and omized to postoperative , once-daily , oral YM150 ( 5 , 10 , 30 , 60 or 120 mg ) ( double-blind ) or preoperative subcutaneous ( open label ) enoxaparin ( 40 mg ) for 5 weeks . The primary efficacy endpoint comprised VTE diagnosed by m and atory bilateral venography or verified symptomatic deep vein thrombosis ( DVT ) plus all deaths up to 9 days after surgery . The primary safety outcome was major bleeding up to 9 days after surgery . RESULTS Primary efficacy endpoint : of 1017 patients r and omized , 960 patients were evaluable for safety and 729 patients for efficacy . A dose-related decrease in VTE incidence from YM150 5 to 60 mg ( P = 0.0005 ) and from 5 to 120 mg ( P = 0.0002 ) was found . The VTE incidence was 27.4 % , 31.7 % , 19.3 % , 13.3 % and 14.5 % for 5 , 10 , 30 , 60 and 120 mg YM150 , respectively , and 18.9 % for enoxaparin . Primary safety endpoint : there was one major bleed with YM150 ( 60 mg ) and one with enoxaparin . CONCLUSIONS The oral direct FXa inhibitor YM150 demonstrated a significant dose response regarding efficacy . Doses from 30 to 120 mg had comparable efficacy to enoxaparin , without compromising safety regarding major bleeding events BACKGROUND Venous thromboembolism ( VTE ) is a common and potential serious complication in lower extremity surgeries , especially in hip and knee arthroplasty . Pulmonary embolism is one of the most fatal complications . The recognition of VTE in the lower limb has been considered as an indication for anticoagulation . Many studies have shown that thrombophilia is one factor of VTE and the most common causes are protein C , protein S and antithrombin III deficiency , factor V leiden and dysfibrinogenemia . VTE is a disease of Western population s because of well documentation of incidence and many studies about thrombophilia . In Thail and , the prevalence of VTE has been unclear . OBJECTIVE The present prospect i ve study evaluated the prevalence of thrombophilia and venous thromboembolism after total knee arthroplasty in patients who did not receive prophylactic treatment of VTE in Phramongkutklao Hospital . STUDY DESIGN Descriptive prospect i ve consecutive case studies . SETTING The Department of Orthopedic Surgery , Phramongkutklao Hospital , Bangkok Thail and . MATERIAL AND METHOD Blood sample was examined at 2 - 3 weeks before TKA for measuring the level of thrombophilia . Bilateral ascending contrast venography of the lower extremities was performed routinely between 6th-10th post operative days after total knee arthroplasty . RESULTS The authors studied 100 patients , 94 primary TKA and 6 revisions TKA . Sixty-one ( 61 % ) were positive for deep vein thrombosis . Eleven patients with positive venograms showed bilateral DVT twelve ( 12 % ) had a proximal DVT one was protein C deficiency , nine were protein S deficiency , 18 were antithrombin III deficiency , and 36 were positive study for FDP(D-dimer ) , However , no one was found with factor V leiden . Odds ratio of protein S deficiency was 0.9506 , Antithrombin III deficiency was 0.7376 , and FDP(D-dimer ) was 1.229 . The protein C deficiency and factor V leiden was undetermined . CONCLUSION Patients who have total knee arthroplasty performed are at high risk for deep venous thrombosis . Although fetal pulmonary embolism rarely occurs in Thai population s , mechanical prevention was routinely used and prophylactic regimen should be a part of management of patients who undergo total knee arthroplasty We carried out an audit on the result of achieving early walking in total knee replacement after instituting a new rehabilitation protocol , and assessed its influence on the development of deep-vein thrombosis as determined by Doppler ultrasound scanning on the fifth post-operative day . Early mobilisation was defined as beginning to walk less than 24 hours after knee replacement . Between April 1997 and July 2002 , 98 patients underwent a total of 125 total knee replacements . They began walking on the second post-operative day unless there was a medical contraindication . They formed a retrospective control group . A protocol which allowed patients to start walking at less than 24 hours after surgery was instituted in August 2002 . Between August 2002 and November 2004 , 97 patients underwent a total of 122 total knee replacements . They formed the early mobilisation group , in which data were prospect ively gathered . The two groups were of similar age , gender and had similar medical comorbidities . The surgical technique and tourniquet times were similar and the same instrumentation was used in nearly all cases . All the patients received low-molecular-weight heparin thromboprophylaxis and wore compression stockings post-operatively . In the early mobilisation group 90 patients ( 92.8 % ) began walking successfully within 24 hours of their operation . The incidence of deep-vein thrombosis fell from 27.6 % in the control group to 1.0 % in the early mobilisation group ( chi-squared test , p < 0.001 ) . There was a difference in the incidence of risk factors for deep-vein thrombosis between the two groups . However , multiple logistic regression analysis showed that the institution of an early mobilisation protocol result ed in a 30-fold reduction in the risk of post-operative deep-vein thrombosis when we adjusted for other risk factors Edoxaban is a new oral direct factor Xa inhibitor . The purpose of this study was to evaluate the efficacy and safety of different doses of edoxaban for the prevention of venous thromboembolism ( VTE ) in patients undergoing elective total hip replacement . A total of 903 patients were r and omised to oral edoxaban 15 , 30 , 60 or 90 mg once daily or subcutaneous dalteparin once daily ( initial dose 2,500 IU , subsequent doses 5,000 IU ) . Both drugs were begun 6 - 8 hours postoperatively and continued for 7 - 10 days , when bilateral venography was performed . The primary efficacy endpoint was the incidence of total VTE , which included proximal and /or distal deep-vein thrombosis ( DVT ) by venography or symptomatic , objective ly confirmed DVT or pulmonary embolism during the treatment period . The primary safety outcome was the incidence of the composite of major and clinical ly relevant non-major bleeding . All venograms and bleeding events were review ed by a central independent adjudication committee blinded as to treatment allocation . Of the 903 patients r and omised , 776 were evaluable for the primary efficacy analysis . The incidences of VTE were 28.2 % , 21.2 % , 15.2 % , and 10.6 % in patients receiving edoxaban 15 , 30 , 60 and 90 mg , respectively , compared with 43.8 % in the dalteparin group ( p<0.005 ) . There was a statistically significant ( p<0.001 ) dose-response for efficacy across the edoxaban dose groups for total VTE and for major VTE . The incidence of clinical ly relevant bleeding was low and similar across the groups . Oral edoxaban once daily is effective for preventing VTE after total hip replacement INTRODUCTION Graduated compression stockings are frequently used following arthroplasty surgery for deep vein thrombosis ( DVT ) prophylaxis . There are often strongly held beliefs regarding whether below-knee or above-knee stockings should be used in total knee joint replacement . Many surgeons argue that below-knee stockings are more likely to induce wound complications because of increased swelling above the stocking and the elastic causing localised pressure on the wound . PATIENTS AND METHODS This study is a prospect i ve comparison of above and below-knee stockings in patients undergoing total knee joint replacement . A total of 50 patients were recruited and studied - 23 patients in the above-knee stocking group and 24 in the below-knee group . Swelling around the knee was measured over the course of an in-patient stay , together with wound complication rates and patients ' preference . RESULTS No statistical difference was found between the groups and no difference in wound complication rates was determined . CONCLUSIONS Below-knee stockings are safe following total knee replacement and are preferred by patients BACKGROUND The American College of Chest Physicians ( ACCP ) guidelines recommends thromboprophylaxis for total hip replacement ( THR ) and total knee replacement ( TKR ) patients . We examined alignment with ACCP thromboprophylaxis guidelines among THR/TKR patients , and compared symptomatic venous thromboembolism ( VTE ) , bleeding event rates and risk factors for VTE between patients receiving ACCP-recommended thromboprophylaxis ( ' ACCP ' ) and those who did not ( ' non-ACCP ' ) . METHODS This retrospective observational study used a large US health plan cl aims data base that was linked to an inpatient data base containing detailed inpatient medication use and a data base containing date -of-death information . Patients who had THR/TKR surgery between April 01 , 2004 and December 31 , 2006 were included . Comparisons of VTE and bleeding events between ACCP and non-ACCP patients were analyzed using chi-squared tests and multivariate logistic regression . RESULTS Of 3,497 linked patients , 1,395 ( 40 % ) received ACCP recommended thromboprophylaxis . Of the patients who received non-ACCP recommended prophylaxis the majority ( 81 % ) received shorter than the recommended minimum 10 day prophylaxis and 118 ( 5.6 % ) of patients received no prophylaxis . Overall , non-ACCP patients were almost twice as likely to experience an incident DVT ( 3.76 % versus 2.01 % , p=0.003 ) and more than eight times as likely to experience an incident PE ( 1.19 % versus 0.14 % , p=0.001 ) relative to ACCP patients ; there were no statistically significant difference in bleeding rates . Multivariate logistic regression indicated that the odds of a VTE event were significantly lower for ACCP patients ( DVT : OR=0.54 ; p=0.006 ; PE : OR=0.12 ; p=0.004 ) . CONCLUSIONS This study offers a unique perspective on ' real-world ' thromboprophylaxis patterns and associated outcomes in THR and TKR patients in the US . It suggests that only 40 % of THR/TKR patients receive ACCP-recommended thromboprophylaxis and that not receiving ACCP thromboprophylaxis is an independent risk factor for both DVT and PE This multicentre dose-finding study compared TAK-442 , an oral factor Xa inhibitor , with enoxaparin for thromboprophylaxis after knee arthroplasty . In this parallel group study , patients were r and omised to oral TAK-442 ( 40 or 80 mg once-daily [ QD ] or 10 , 20 , 40 , or 80 mg twice-daily [ BID ] started 6 - 8 hours postoperatively ) , which was blinded as to dose , or to open-label subcutaneous enoxaparin ( 30 mg BID starting 12 - 24 hours postoperatively ) for 10 days . Treatments were continued until bilateral venography was performed ( maximum of 14 days ) . The primary efficacy endpoint was the composite of any deep-vein thrombosis , non-fatal pulmonary embolism or all-cause mortality , while the primary safety endpoint was major bleeding . Of 1,038 patients r and omised who received at least one dose of study drug , 949 completed the study and 730 ( 76.9 % ) were evaluable for the primary efficacy analysis . Recruitment into the 10 and 20 mg BID dose groups was stopped early because the incidences of the primary efficacy endpoint were significantly higher than that with enoxaparin . The primary efficacy endpoint occurred in 22.0 % of patients given enoxaparin and in 39.0 % , 38.4 % , 23.5 % , 21.4 % , 26.8 % , and 14.3 % of those receiving TAK-442 10 mg BID , 20 mg BID , 40 mg QD , 40 mg BID , 80 mg QD , and 80 mg BID , respectively . The incidences of major and clinical ly relevant non-major bleeding with TAK-442 were not dose-dependent or different from that with enoxaparin . All TAK-442 doses except 10 and 20 mg BID displayed similar efficacy and safety profiles to enoxaparin BACKGROUND Venous thromboembolism ( VTE ) remains a significant complication of major orthopedic surgery , and chronic kidney disease ( CKD ) is common among elderly patients undergoing total hip replacement ( THR ) . OBJECTIVES The purpose of this study was to evaluate thrombosis and bleeding outcomes in patients with stage 3B CKD treated with either desirudin or enoxaparin after elective THR . PATIENTS / METHODS This was a post hoc subgroup analysis of a r and omized , multicenter , double-blind study of desirudin vs. enoxaparin in patients undergoing elective THR . RESULTS Patients received either subcutaneous desirudin 15 mg twice daily or subcutaneous enoxaparin 40 mg once daily . Of the 2078 r and omized patients who received study medication , 577 had stage 3B CKD or worse ( 27.8 % ) , and the proportion of these patients who experienced a major VTE in the enoxaparin treatment group was found to be much higher than in the desirudin treatment group ( 11.1 % vs. 3.4 % , model-adjusted odds ratio 3.52 , 95 % confidence interval 1.48 - 8.40 , P=0.004 ) . There was no statistically significant difference between treatment groups in terms of rates of major bleeding , regardless of stage of renal function . CONCLUSIONS CKD has been reported previously to increase the risk of bleeding with anticoagulants , and these findings suggest that CKD may also increase the risk of major VTE for patients treated with enoxaparin , but not for patients treated with desirudin . Clinicians should consider the impact of CKD on the risk of VTE when choosing a prophylaxis agent OBJECTIVE To evaluate risk factors for venous thromboembolism ( VTE ) despite thromboprophylaxis in major orthopedic surgery patients at a tertiary care hospital . METHODS Charts from consecutive patients who underwent total hip replacement ( THR ) , total knee replacement ( TKR ) , or hip fracture surgery ( HFS ) [ hip pinning or hemiarthroplasty ] from August 1 , 1999 , to April 30 , 2000 , at a large Canadian teaching hospital were abstract ed using st and ardized case report forms . Data were collected on patient characteristics , surgical characteristics , and thromboprophylaxis regimen . Results of tests performed for suspected VTE were documented . Associations between characteristics of interest and objective ly confirmed VTE were examined in multivariate analysis . RESULTS Over the study period , 310 patients underwent major orthopedic surgery and received st and ard thromboprophylaxis with either dalteparin or enoxaparin ( mean duration of prophylaxis , 7 days ) . Of these , 34 % underwent THR , 30 % underwent TKR , and 36 % underwent HFS . Of 83 suspected cases of VTE , 44 cases ( 7 proximal and 37 distal deep venous thrombosis [ DVT ] ) ; 14 % of study population ) were confirmed with objective testing . Multivariate analyses revealed that knee surgery ( odds ratio [ OR ] , 4.8 ; 95 % confidence interval [ CI ] , 2.3 to 10.1 ) and type of low molecular weight heparin ( LMWH ) [ enoxaparin ( more protective ) : OR , 0.39 ; 95 % CI , 0.20 to 0.80 ] independently predicted VTE . No patient characteristics ( including previous VTE , malignancy , hormonal therapy , postoperative complications ) were associated with VTE . CONCLUSION Despite st and ard thromboprophylaxis , symptomatic breakthrough VTE , primarily distal DVT , developed in 14 % of patients undergoing major orthopedic surgery . Factors that independently predicted VTE in our population were TKR surgery and type of LMWH . TKR patients may warrant more aggressive postoperative physiotherapy and ambulation and adjunctive prophylactic measures such as pneumatic compression . Due to the heterogeneity of different LMWH compounds , direct comparison of the effectiveness of enoxaparin with dalteparin for orthopedic prophylaxis in prospect i ve , r and omized trials seems warranted INTRODUCTION The optimal duration of thromboprophylaxis after total knee arthroplasty remains uncertain . MATERIAL AND METHODS We performed a r and omized , open trial to determine whether to stop thromboprophylactic therapy at Day 10±2 ( ' short thromboprophylaxis ' ) was non-inferior to continue thromboprophylactic therapy up to Day 35±5 ( ' extended thromboprophylaxis ' ) after total knee arthroplasty . At Day 7±2 , subjects were screened by ultrasonography for asymptomatic deep-vein thrombosis and r and omized . The primary outcome was a composite of proximal deep-vein thrombosis , any symptomatic deep-vein thrombosis , non-fatal symptomatic pulmonary embolism , major bleeding , heparin-induced thrombocytopenia , or all-cause death up to Day 35±5 . The secondary outcome was ultrasonographic ( extension or new onset ) distal deep-vein thrombosis at Day 35±5 . RESULTS Twenty-one patients ( 2.4 % ) were not r and omized , because of asymptomatic proximal deep-vein thrombosis on systematic ultrasonography at Day 7±2 . Among the 857 r and omized patients , mean ( SD ) duration of anticoagulant treatment was 11.2 ( 6.7 ) and 33.9 ( 3.7 ) days in the short and extended thromboprophylaxis groups , respectively . The respective rates of the primary outcome were 4.0 % ( 17/420 ) and 2.4 % ( 10/422 ) , with an absolute difference of 1.7 % ( 90 % confidence interval , -0.3 to 3.7 ) . In 285 patients with asymptomatic distal deep-vein thrombosis at Day 7±2 , the respective rates of the primary outcome were 7.8 % and 2.8 % ( p=0.067 ) . The rates of the secondary outcome were 14.8 % ( 62/420 ) and 4.5 % ( 19/422 ) , respectively ( p<0.001 ) . CONCLUSIONS Short thromboprophylaxis was not non-inferior to extended thromboprophylaxis after total knee arthroplasty . In this setting , the thromboembolic risk persisted longer than seven days , notably in patients with asymptomatic distal deep-vein thrombosis at discharge . Clinical Trials.gov number : NCT00362492 BACKGROUND TB-402 is a novel anticoagulant monoclonal antibody with a prolonged antithrombotic effect result ing from its partial factor (F)VIII inhibition and long half-life . We evaluated the efficacy and safety of a single administration of TB-402 for the prevention of venous thromboembolism ( VTE ) after total knee replacement ( TKR ) . PATIENTS AND METHODS This was a phase II , dose-escalating , r and omized , enoxaparin-controlled , open-label study . Patients were post-operatively assigned to a single dose of TB-402 ( 0.3 , 0.6 or 1.2 mg kg(-1 ) ) or enoxaparin 40 mg for at least 10 days ( n = 75 per group ; 3:1 TB-402 to enoxaparin ) . The primary efficacy outcome was total VTE defined as asymptomatic deep vein thrombosis ( DVT ) detected by bilateral venography and symptomatic VTE by day 7 to 11 . The principal safety outcome was the incidence of major bleeding and clinical ly relevant non-major bleeding . RESULTS Total VTE was lower in all TB-402 groups compared with enoxaparin : 16.7%(95 % CI 9.8 - 26.9 ) , 23.9%(95 % CI 15.3 - 35.3 ) , 24.1%(95 % CI 16.0 - 34.5 ) and 39.0%(95 % CI 28.8 - 50.1 ) for TB-402 0.3 , 0.6 , 1.2 mg kg(-1 ) and enoxaparin , respectively ( P = 0.003 for TB-402 0.3 mg kg(-1 ) vs. enoxaparin ) . The incidence of total VTE in the pooled TB-402 groups was 21.6 % ( 95%CI 16.6 - 27.5 ) , an absolute risk reduction vs. enoxaparin of 17.4 % ( 95 % CI 5.2 - 29.6 ) . Major or clinical ly relevant non-major bleeding was observed in 3/75(4.0 % ) , 4/74(5.4 % ) , 7/87(8.0 % ) and 3/79(3.8 % ) patients for TB-402 0.3 , 0.6 , 1.2 mg kg(-1 ) and enoxaparin , respectively . CONCLUSIONS TB-402 , as a single post-operative administration , was associated with a lower rate of VTE in all doses tested , compared with enoxaparin . The incidence of major and clinical ly relevant non-major bleeding was similar to enoxaparin 40 mg for TB-402 0.3 and 0.6 mg kg(-1 ) BACKGROUND LY517717 is an oral direct inhibitor of activated factor X that is currently under clinical development . OBJECTIVES The aims of this proof-of-concept study in patients undergoing total knee replacement ( TKR ) or total hip replacement ( THR ) were to determine whether LY517717 can safely reduce the risk of venous thromboembolism ( VTE ) and to identify at least one dose of LY517717 that is non-inferior to enoxaparin . METHODS In a double-blind , parallel-arm , dose-ranging study , patients undergoing TKR or THR were r and omly allocated to receive once-daily oral LY517717 ( 25 , 50 , 75 , 100 , 125 or 150 mg ) , started 6 - 8 h after wound closure , or s.c . enoxaparin , 40 mg , started in the evening before surgery . The primary efficacy endpoint was the composite of deep venous thrombosis ( DVT ) , detected by m and atory bilateral venography performed at the end of the study treatment ( between days 5 and 9 ) , and objective ly confirmed symptomatic DVT and /or pulmonary embolism ( PE ) , occurring during the treatment period . The combination of major and minor bleeding was the primary safety endpoint . RESULTS Five hundred and seven patients received at least one dose of LY517717 or enoxaparin ( safety population ) . Three hundred and ninety-one patients had evaluable bilateral venography or experienced a clinical DVT and /or PE ( primary efficacy population ) . LY517717 treatment result ed in a dose-dependent decrease in the incidence of thromboembolic events ( P = 0.0001 ) . The incidences of VTE with 100 , 125 , and 150 mg of LY517717 were 19 % , 19 % and 16 % , respectively , compared to 21 % with enoxaparin . The efficacies of 100-mg , 125-mg and 150-mg doses of LY517717 were non-inferior to that of enoxaparin according to prespecified criteria . Bleeding events were uncommon in both LY517717 and enoxaparin patients . CONCLUSIONS Doses of 100 , 125 and 150 mg of LY517717 are non-inferior to enoxaparin for the prevention of VTE after TKR or THR , and are associated with similar low rates of bleeding BACKGROUND The optimal method of prophylaxis for the prevention of pulmonary embolism in patients undergoing total hip arthroplasty remains controversial . Guidelines appear to be contradictory . The purpose of the present study was to examine whether a best prophylactic agent exists for the prevention of postoperative pulmonary embolism and whether the type of anesthesia affects the rates of pulmonary embolism . METHODS From 2001 to 2008 , a total joint registry from a nationwide health maintenance organization was evaluated to determine the rates of pulmonary embolism , fatal pulmonary embolism , and death among 17,595 patients without a history of venous thromboembolism who were managed with unilateral total hip arthroplasty . All patients were followed for ninety days postoperatively . Data were abstract ed electronically and were vali date d through chart review s. Multivariate logistic regression models were used to assess associations between the types of prophylaxis and anesthesia that were used and pulmonary embolism while adjusting for other risk factors . RESULTS Patients received either mechanical prophylaxis alone ( N = 1533 ) or chemical prophylaxis ( aspirin [ N = 934 ] , Coumadin [ warfarin ] [ N = 6063 ] , or low-molecular-weight heparin [ N = 7202 ] ) with or without mechanical prophylaxis . The rate of pulmonary embolism was 0.41 % ( 95 % confidence interval [ CI ] , 0.32 % to 0.51 % ) overall , 0.37 % ( 95 % CI , 0.05 % to 0.70 % ) for mechanical prophylaxis , 0.43 % ( 95 % CI , 0.01 % to 0.85 % ) for aspirin , 0.43 % ( 95 % CI , 0.26 % to 0.59 % ) for Coumadin , 0.40 % ( 95 % CI , 0.26 % to 0.55 % ) for low-molecular-weight heparin , 0.43 % ( 95 % CI , 0.28 % to 0.58 % ) for general anesthesia , and 0.40 % ( 95 % CI , 0.28 % to 0.52 % ) for non-general anesthesia . The mortality rate was 0.51 % ( 95 % CI , 0.40 % to 1.01 % ) overall , 0.67 % ( 95 % CI , 0.23 % to 1.34 % ) for mechanical prophylaxis , 0.64 % ( 95 % CI , 0.13 % to 1.28 % ) for aspirin , 0.51 % ( 95 % CI , 0.33 % to 1.02 % ) for Coumadin , 0.42 % ( 95 % CI , 0.27 % to 0.83 % ) for low-molecular-weight heparin , 0.51 % ( 95 % CI , 0.35 % to 0.67 % ) for general anesthesia , and 0.50 % ( 95 % CI , 0.36 % to 0.64 % ) for non-general anesthesia . Regression models did not show any association between the type of prophylaxis used or the choice of anesthesia and increased odds of pulmonary embolism when adjusting for age , sex , and American Society of Anesthesiologists score . CONCLUSIONS No clinical differences were detected among the types of prophylaxis against venous thromboembolism or the types of anesthesia with respect to pulmonary embolism , fatal pulmonary embolism , or death on the basis of prospect i ve collection of data by a contemporary total joint registry A total of 110 total knee replacements ( TKRs ) was r and omised to receive either a cemented or an uncemented prosthesis . Postoperative venography at five to seven days was used to compare the prevalence , site and size of deep-vein thrombosis ( DVT ) . We also compared the findings with those of postoperative venography in a group of patients with cemented total hip replacements ( THRs ) . The total prevalence of DVT was significantly greater after uncemented ( 81 % ) than after cemented TKR ( 55 % ) . Both knee groups had a significantly higher prevalence of DVT than in cemented hip replacements ( 32 % ) . We found no difference in the proportion with proximal DVT in the three groups ( 14 % , 15 % and 16 % ) . The median length of the thrombi was significantly greater after cemented ( 26.5 cm ) than after uncemented TKR ( 11 cm ) or after cemented THR ( 7 cm ) . This difference was mainly due to greater lengths of distal rather than proximal thrombi . We conclude that the use of cement may affect the formation of DVT after joint replacement , but does not appear to lead to an increased incidence Dabigatran , an oral once-daily unmonitored thrombin inhibitor , has been tested elsewhere using enoxaparin 40 mg once daily . We used the North American enoxaparin 30 mg BID regimen as the comparator . This was a double-blind , central ly r and omized trial . Unilateral total knee arthroplasty patients were r and omized to receive oral dabigatran etexilate 220 or 150 mg once daily , or enoxaparin 30 mg SC BID after surgery , blinded . Dosing stopped at contrast venography , 12 to 15 days after surgery . Among 1896 patients , dabigatran 220 and 110 mg showed inferior efficacy to enoxaparin ( venous thromboembolism rates of 31 % [ P = .02 vs enoxaparin ] , 34 % [ P < .001 vs enoxaparin ] , and 25 % , respectively ) . Bleeding rates were similar , and no drug-related hepatic illness was recognized . Dabigatran , effective compared to once-daily enoxaparin , showed inferior efficacy to the twice-daily North American enoxaparin regimen , probably because of the latter 's more intense and prolonged dosing BACKGROUND We investigated the efficacy of rivaroxaban , an orally active direct factor Xa inhibitor , in preventing venous thrombosis after total knee arthroplasty . METHODS In this r and omized , double-blind trial , 2531 patients who were to undergo total knee arthroplasty received either oral rivaroxaban , 10 mg once daily , beginning 6 to 8 hours after surgery , or subcutaneous enoxaparin , 40 mg once daily , beginning 12 hours before surgery . The primary efficacy outcome was the composite of any deep-vein thrombosis , nonfatal pulmonary embolism , or death from any cause within 13 to 17 days after surgery . Secondary efficacy outcomes included major venous thromboembolism ( i.e. , proximal deep-vein thrombosis , nonfatal pulmonary embolism , or death related to venous thromboembolism ) and symptomatic venous thromboembolism . The primary safety outcome was major bleeding . RESULTS The primary efficacy outcome occurred in 79 of 824 patients ( 9.6 % ) who received rivaroxaban and in 166 of 878 ( 18.9 % ) who received enoxaparin ( absolute risk reduction , 9.2 % ; 95 % confidence interval [ CI ] , 5.9 to 12.4 ; P<0.001 ) . Major venous thromboembolism occurred in 9 of 908 patients ( 1.0 % ) given rivaroxaban and 24 of 925 ( 2.6 % ) given enoxaparin ( absolute risk reduction , 1.6 % ; 95 % CI , 0.4 to 2.8 ; P=0.01 ) . Symptomatic events occurred less frequently with rivaroxaban than with enoxaparin ( P=0.005 ) . Major bleeding occurred in 0.6 % of patients in the rivaroxaban group and 0.5 % of patients in the enoxaparin group . The incidence of drug-related adverse events , mainly gastrointestinal , was 12.0 % in the rivaroxaban group and 13.0 % in the enoxaparin group . CONCLUSIONS Rivaroxaban was superior to enoxaparin for thromboprophylaxis after total knee arthroplasty , with similar rates of bleeding . ( Clinical Trials.gov number , NCT00361894 . The use of cement is considered as an important way to control perioperative blood loss in knee arthroplasty . We prospect ively r and omized 57 patients ( 60 knees ) who underwent total knee arthroplasty with ( 30 knees ) or without ( 30 knees ) tibial cement to evaluate perioperative blood loss . The measured total blood loss did not differ significantly between the 2 groups ( with tibial cement , 731 + /- 288 mL ; without cement , 731 + /- 331 mL ; P = .9117 ) . The red blood cell count , hemoglobin level , and hematocrit returned to the preoperative levels within 3 months in both groups . Therefore , tibial cement does not appear to affect perioperative blood loss . This finding has implication s when planning blood replacement in cementless and hybrid-type arthroplasties BACKGROUND Low-molecular-weight heparins such as enoxaparin are preferred for prevention of venous thromboembolism after major joint replacement . Apixaban , an orally active factor Xa inhibitor , might be as effective , have lower bleeding risk , and be easier to use than is enoxaparin . We assessed efficacy and safety of these drugs after elective total knee replacement . METHODS In ADVANCE-2 , a multicentre , r and omised , double-blind phase 3 study , patients undergoing elective unilateral or bilateral total knee replacement were r and omly allocated through an interactive central telephone system to receive oral apixaban 2.5 mg twice daily ( n=1528 ) or subcutaneous enoxaparin 40 mg once daily ( 1529 ) . The r and omisation schedule was generated by the Bristol-Myers Squibb r and omisation centre and stratified by study site and by unilateral or bilateral surgery with a block size of four . Investigators , patients , statisticians , adjudicators , and steering committee were masked to allocation . Apixaban was started 12 - 24 h after wound closure and enoxaparin 12 h before surgery ; both drugs were continued for 10 - 14 days , when bilateral ascending venography was scheduled . Primary outcome was the composite of asymptomatic and symptomatic deep vein thrombosis , non-fatal pulmonary embolism , and all-cause death during treatment . The statistical plan required non-inferiority of apixaban before testing for superiority ; analysis was by intention to treat for non-inferiority testing . The study is registered at Clinical Trials.gov , number NCT00452530 . FINDINGS 1973 of 3057 patients allocated to treatment ( 1528 apixaban , 1529 enoxaparin ) were eligible for primary efficacy analysis . The primary outcome was reported in 147 ( 15 % ) of 976 apixaban patients and 243 ( 24 % ) of 997 enoxaparin patients ( relative risk 0.62 [ 95 % CI 0.51 - 0.74 ] ; p<0.0001 ; absolute risk reduction 9.3 % [ 5.8 - 12.7 ] ) . Major or clinical ly relevant non-major bleeding occurred in 53 ( 4 % ) of 1501 patients receiving apixaban and 72 ( 5 % ) of 1508 treated with enoxaparin ( p=0.09 ) . INTERPRETATION Apixaban 2.5 mg twice daily , starting on the morning after total knee replacement , offers a convenient and more effective orally administered alternative to 40 mg per day enoxaparin , without increased bleeding . FUNDING Bristol-Myers Squibb ; Pfizer BACKGROUND This phase 3 trial compared the efficacy and safety of rivaroxaban , an oral direct inhibitor of factor Xa , with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty . METHODS In this r and omized , double-blind study , we assigned 4541 patients to receive either 10 mg of oral rivaroxaban once daily , beginning after surgery , or 40 mg of enoxaparin subcutaneously once daily , beginning the evening before surgery , plus a placebo tablet or injection . The primary efficacy outcome was the composite of deep-vein thrombosis ( either symptomatic or detected by bilateral venography if the patient was asymptomatic ) , nonfatal pulmonary embolism , or death from any cause at 36 days ( range , 30 to 42 ) . The main secondary efficacy outcome was major venous thromboembolism ( proximal deep-vein thrombosis , nonfatal pulmonary embolism , or death from venous thromboembolism ) . The primary safety outcome was major bleeding . RESULTS A total of 3153 patients were included in the superiority analysis ( after 1388 exclusions ) , and 4433 were included in the safety analysis ( after 108 exclusions ) . The primary efficacy outcome occurred in 18 of 1595 patients ( 1.1 % ) in the rivaroxaban group and in 58 of 1558 patients ( 3.7 % ) in the enoxaparin group ( absolute risk reduction , 2.6 % ; 95 % confidence interval [ CI ] , 1.5 to 3.7 ; P<0.001 ) . Major venous thromboembolism occurred in 4 of 1686 patients ( 0.2 % ) in the rivaroxaban group and in 33 of 1678 patients ( 2.0 % ) in the enoxaparin group ( absolute risk reduction , 1.7 % ; 95 % CI , 1.0 to 2.5 ; P<0.001 ) . Major bleeding occurred in 6 of 2209 patients ( 0.3 % ) in the rivaroxaban group and in 2 of 2224 patients ( 0.1 % ) in the enoxaparin group ( P=0.18 ) . CONCLUSIONS A once-daily , 10-mg oral dose of rivaroxaban was significantly more effective for extended thromboprophylaxis than a once-daily , 40-mg subcutaneous dose of enoxaparin in patients undergoing elective total hip arthroplasty . The two drugs had similar safety profiles . ( Clinical Trials.gov number , NCT00329628 . BACKGROUND The optimal strategy for thromboprophylaxis after major joint replacement has not been established . Low-molecular-weight heparins such as enoxaparin predominantly target factor Xa but to some extent also inhibit thrombin . Apixaban , a specific factor Xa inhibitor , may provide effective thromboprophylaxis with a low risk of bleeding and improved ease of use . METHODS In a double-blind , double-dummy study , we r and omly assigned patients undergoing total knee replacement to receive 2.5 mg of apixaban orally twice daily or 30 mg of enoxaparin subcutaneously every 12 hours . Both medications were started 12 to 24 hours after surgery and continued for 10 to 14 days . Bilateral venography was then performed . The primary efficacy outcome was a composite of asymptomatic and symptomatic deep-vein thrombosis , nonfatal pulmonary embolism , and death from any cause during treatment . Patients were followed for 60 days after anticoagulation therapy was stopped . RESULTS A total of 3195 patients underwent r and omization , with 1599 assigned to the apixaban group and 1596 to the enoxaparin group ; 908 subjects were not eligible for the efficacy analysis . The overall rate of primary events was much lower than anticipated . The rate of the primary efficacy outcome was 9.0 % with apixaban as compared with 8.8 % with enoxaparin ( relative risk , 1.02 ; 95 % confidence interval , 0.78 to 1.32 ) . The composite incidence of major bleeding and clinical ly relevant nonmajor bleeding was 2.9 % with apixaban and 4.3 % with enoxaparin ( P=0.03 ) . CONCLUSIONS As compared with enoxaparin for efficacy of thromboprophylaxis after knee replacement , apixaban did not meet the prespecified statistical criteria for noninferiority , but its use was associated with lower rates of clinical ly relevant bleeding and it had a similar adverse-event profile . ( Clinical Trials.gov number , NCT00371683 . BACKGROUND There are various regimens for thromboprophylaxis after hip replacement . Low-molecular-weight heparins such as enoxaparin predominantly inhibit factor Xa but also inhibit thrombin to some degree . Orally active , specific factor Xa inhibitors such as apixaban may provide effective thromboprophylaxis with a lower risk of bleeding and improved ease of use . METHODS In this double-blind , double-dummy study , we r and omly assigned 5407 patients undergoing total hip replacement to receive apixaban at a dose of 2.5 mg orally twice daily or enoxaparin at a dose of 40 mg subcutaneously every 24 hours . Apixaban therapy was initiated 12 to 24 hours after closure of the surgical wound ; enoxaparin therapy was initiated 12 hours before surgery . Prophylaxis was continued for 35 days after surgery , followed by bilateral venographic studies . The primary efficacy outcome was the composite of asymptomatic or symptomatic deep-vein thrombosis , nonfatal pulmonary embolism , or death from any cause during the treatment period . Patients were followed for an additional 60 days after the last intended dose of study medication . RESULTS A total of 1949 patients in the apixaban group ( 72.0 % ) and 1917 patients in the enoxaparin group ( 71.0 % ) could be evaluated for the primary efficacy analysis . The primary efficacy outcome occurred in 27 patients in the apixaban group ( 1.4 % ) and in 74 patients in the enoxaparin group ( 3.9 % ) ( relative risk with apixaban , 0.36 ; 95 % confidence interval [ CI ] , 0.22 to 0.54 ; P<0.001 for both noninferiority and superiority ; absolute risk reduction , 2.5 percentage points ; 95 % CI , 1.5 to 3.5 ) . The composite outcome of major and clinical ly relevant nonmajor bleeding occurred in 129 of 2673 patients assigned to apixaban ( 4.8 % ) and 134 of 2659 assigned to enoxaparin ( 5.0 % ) ( absolute difference in risk , -0.2 percentage points ; 95 % CI , -1.4 to 1.0 ) . CONCLUSIONS Among patients undergoing hip replacement , thromboprophylaxis with apixaban , as compared with enoxaparin , was associated with lower rates of venous thromboembolism , without increased bleeding . ( Funded by Bristol-Myers Squibb and Pfizer ; Clinical Trials.gov number , NCT00423319 . ) OBJECTIVES This study assessed the dose response of SR123781A for the prevention of venous thromboembolism ( VTE ) in patients undergoing total hip replacement ( THR ) surgery . BACKGROUND Despite VTE preventive measures , residual VTE complications still occur after THR . SR123781A , a synthetic oligosaccharide with a mixed profile of anti-factor Xa and IIa activities , could be an alternative to current treatments . METHODS In this double-blind study , 1,023 patients undergoing THR were r and omly assigned to 1 of 5 daily doses of SR123781A or to a calibrator arm of enoxaparin 40 mg . Treatment was continued for 10 days or until bilateral venography was performed after a minimum of 5 days . RESULTS A significant dose-response effect for VTE was observed for SR123781A ( p < 0.0001 ) . The VTE rates were 21.2 % , 17.7 % , 13.5 % , 7.0 % , and 4.4 % in the 0.25- , 0.5- , 1.0- , 2.0- , and 4.0-mg dose groups of SR123781A , respectively , and 8.7 % in the enoxaparin group . Doses of 2.0 and 4.0 mg of SR123781A reduced the risk of VTE by 67 % and 79 % , respectively , compared with the 0.25-mg dose group . Major bleeding was observed in 1.2 % , 0.6 % , 0.6 % , 0.6 % , and 5.8 % of the patients in the 0.25- , 0.5- , 1.0- , 2.0- , and 4.0-mg dose groups of SR123781A , respectively , and in 0.6 % of patients in the enoxaparin group . The dose-response effect for major bleeding was significant ( p = 0.0037 ) . CONCLUSIONS The model based on these dose-finding study results suggests that SR123781A doses ranging from 1.5 to 2.5 mg show a reasonable risk-to-benefit ratio for VTE prevention after major orthopedic surgery BACKGROUND AVE5026 is a new hemisynthetic ultra-low-molecular-weight heparin , with a novel anti-thrombotic profile result ing from high anti-factor (F)Xa activity and residual anti-FIIa activity . AVE5026 is in clinical development for venous thromboembolism ( VTE ) prevention , a frequent complication after total knee replacement ( TKR ) surgery . OBJECTIVES This study evaluated the dose-response of AVE5026 for the prevention of VTE in patients undergoing TKR surgery . PATIENTS / METHODS In this parallel-group , double-blind , double-dummy study , 690 patients were r and omized , and 678 treated with once-daily doses of AVE5026 ( 5 , 10 , 20 , 40 , or 60 mg ) or enoxaparin 40 mg in the calibrator arm . The primary efficacy end point was VTE until post-operative day 11 , defined as deep vein thrombosis ( DVT ) detected by bilateral venography , symptomatic DVT , non-fatal pulmonary embolism ( PE ) and VTE-related death . The primary safety outcome was the incidence of major bleeding . RESULTS The primary efficacy outcome was assessed in 464 patients . There was a significant dose-response across the five AVE5026 groups for VTE prevention ( P<0.0001 ) , with the incidence of VTE ranging from 5.3 % to 44.1 % compared with 35.8 % in the enoxaparin group and for proximal DVT ( P=0.0002 ) . Also , a significant dose-response for AVE5026 was seen for major bleeding ( P=0.0231 ) and any bleeding ( P=0.0003 ) . Six patients in the AVE5026 groups , four in the 60 mg group , experienced major bleeding ; none did in the enoxaparin group . CONCLUSIONS The safety and efficacy results of this study suggest that a AVE5026 dose of between 20 and 40 mg presents an adequate benefit-to-risk ratio |
13,593 | 27,764,237 | A pilot test of our newly developed patient education program with 13 participants showed excellent comprehensibility and the MS-specific content was judged as very important .
Development and pilot-testing of an evidence -based patient education program on nutrition and MS is feasible .
Patient satisfaction with the program suffers from the lack of evidence . | BACKGROUND Dietary factors have been discussed to influence risk or disease course of multiple sclerosis ( MS ) .
Specific diets are widely used among patients with MS .
OBJECTIVE To design and pilot-test an evidence based patient education program on dietary factors in MS . | Multiple sclerosis ( MS ) presents with optic neuritis ( ON ) in 20 % of cases and 50 % of ON patients develop MS within 15 years . In this study , we evaluated the preventive effects of vitamin D3 administration on the conversion of ON to MS ( primary outcome ) and on the MRI lesions ( secondary outcome ) of ON patients with low serum 25 ( OH ) D levels . Thirty ON patients ( 15 in each of 2 groups , aged 20–40 years ) with serum 25 ( OH ) D levels of less than 30 ng/ml were enrolled in a double blind , r and omized , parallel-group trial . The treatment group ( cases ) received 50,000 IU of vitamin D3 weekly for 12 months and the control group ( controls ) received a placebo weekly for 12 months . Finally , the subsequent relapse rate and changes in MRI plaques were compared between the two groups . Risk reduction was 68.4 % for the primary outcome in the treatment group ( relative risk = 0.316 , p = 0.007 ) . After 12 months , patients in the treatment group had a significantly lower incidence rate of cortical , juxtacortical , corpus callosal , new T2 , new gadolinium-enhancing lesions and black holes . The mean number of total plaques showed a marginally significant decrease in the group receiving vitamin D3 supplementation as compared with the placebo group ( p = 0.092 ) . Administration of vitamin D3 supplements to ON patients with low serum vitamin 25 ( OH ) D levels may delay the onset of a second clinical attack and the subsequent conversion to MS Background Flu-like symptoms ( FLS ) are common side effects of interferon beta ( IFN-β ) treatment in patients with Multiple Sclerosis ( PwMS ) and are associated with post-injection cytokine surge . We hypothesized that vitamin D3 supplementation would ameliorate FLS by decreasing related serum cytokines ’ levels . Methods In a r and omized , double blind study of 45 IFNβ-treated PwMS , 21 patients were assigned to 800 IU of vitamin D3 per day ( low dose ) , while 24 patients received 4,370 IU per day ( high dose ) for one year . FLS were assessed monthly by telephonic interviews . Serum levels of 25-hydroxy-D ( 25-OH-D ) , calcium , PTH , IL-17 , IL-10 and IFN-γ were measured periodically . EDSS , relapses , adverse events and quality of life ( QoL ) were documented . Results 25-OH-D levels increased to a significantly higher levels and PTH levels decreased in the high dose group . There was no significant change in FLS . IL-17 levels were significantly increased in the low dose group , while patients receiving high dose vitamin D had a heterogeneous IL-17 response . No significant differences in relapse rate , EDSS , QoL , serum IL-10 and IFNγ were found . Hypercalcemia or other potential major adverse events were not observed . Conclusion Vitamin D supplementation to IFN−β treated PwMS , at the doses used , seems safe and associated with dose-dependent changes in IL-17 serum levels , while not affecting IFN−β related FLS.Trial registration Clinical Trials.gov ID : Abstract Objectives To explore the association between dietary factors including fat , fruit and vegetable intake , dairy and meat consumption , and health-related quality of life ( HRQOL ) , disability and relapse rate in a large international sample of people with multiple sclerosis ( MS ) . Methods Participants with MS were recruited to the study via Web 2.0 platforms and completed a comprehensive survey measuring demographic and clinical characteristics , HRQOL , disability , relapse rate , and the Diet Habits Question naire ( DHQ ) . Results Of 2469 participants with confirmed MS , 2087 ( 84.5 % ) provided complete data on their dietary habits ( DHQ total score ) . Multivariate regression models demonstrated that every 10-point increase on the DHQ total score was associated with nearly a six-point and five-point increase in physical and mental HRQOL , respectively , and 30.0 % reduced likelihood of a higher level of disability . After controlling for age and gender , and the other dietary covariates , ‘ healthy ’ consumption of fruit and vegetables and dietary fat predicted better quality of life and less likelihood of higher disability when compared to respondents with a ‘ poor ’ diet . For those with relapsing – remitting MS , the DHQ total significantly predicted a lower relapse rate and reduced odds of increasing disease activity , but the model fit was poor and the predicted change only marginal . Discussion This study supports significant associations of healthy dietary habits with better physical and mental HRQOL and a lower level of disability . Further research is urgently required to explore these associations including r and omized controlled trials of dietary modification for people with MS Seventy-five patients in London and Belfast with multiple sclerosis were given daily supplements of a vegetable oil mixture containing either linoleate or oleate for two years in a double-blind control trial . Relapses tended to be less frequent and were significantly less severe and of shorter duration in the linoleate-supplemented group than in those receiving the oleate mixture , but clear evidence that treatment affected the overall rate of clinical deterioration was not obtained Objective : Low vitamin D status has been associated with multiple sclerosis ( MS ) prevalence and risk , but the therapeutic potential of vitamin D in established MS has not been explored . Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical , immunologic , and clinical outcomes in patients with MS prospect ively . Methods : An open-label r and omized prospect i ve controlled 52-week trial matched patients with MS for demographic and disease characteristics , with r and omization to treatment or control groups . Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [ 25(OH)D ] rapidly and assess tolerability , followed by 10,000 IU/day ( 12 weeks ) , and further downtitrated to 0 IU/day . Calcium ( 1,200 mg/day ) was given throughout the trial . Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups . Secondary endpoints included 25(OH)D and other biochemical measures , immunologic biomarkers , relapse events , and Exp and ed Disability Status Scale ( EDSS ) score . Results : Forty-nine patients ( 25 treatment , 24 control ) were enrolled [ mean age 40.5 years , EDSS 1.34 , and 25(OH)D 78 nmol/L ] . All calcium-related measures within and between groups were normal . Despite a mean peak 25(OH)D of 413nmol/L , no significant adverse events occurred . Although there may have been confounding variables in clinical outcomes , treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls . Conclusions : High-dose vitamin D ( ∼10,000 IU/day ) in multiple sclerosis is safe , with evidence of immunomodulatory effects . Classification of evidence : This trial provides Class II evidence that high-dose vitamin D use for 52 weeks in patients with multiple sclerosis does not significantly increase serum calcium levels when compared to patients not on high-dose supplementation . The trial , however , lacked statistical precision and the design requirements to adequately assess changes in clinical disease measures ( relapses and Exp and ed Disability Status Scale scores ) , providing only Class level IV evidence for these outcomes The aim of this preliminary study was to evaluate the effect of low-dose oral vitamin D in combination with current disease-modifying therapy on the prevention of progression of relapsing-remitting multiple sclerosis ( RRMS ) . A phase II double-blind placebo-controlled r and omized clinical trial conducted between October 2007 and October 2008 included 50 patients with confirmed RRMS aged 25 to 57 years and normal serum 25-hydroxyvitamin D. They were r and omly allocated to receive 12 months of treatment with either escalating calcitriol doses up to 0.5 μg/day or placebo combined with disease-modifying therapy . Response to treatment was assessed at eight-week intervals . In both groups , the mean relapse rate decreased significantly ( P < 0.001 ) . In the 25 patients treated with placebo , the mean ( SD ) Exp and ed Disability Status Scale ( EDSS ) increased from 1.70 ( 1.21 ) at baseline to 1.94 ( 1.41 ) at the end of study period ( P < 0.01 ) . Average EDSS and relapse rate at the end of trial did not differ between groups . Adding low-dose vitamin D to routine disease-modifying therapy had no significant effect on the EDSS score or relapse rate . A larger phase III multicenter study of vitamin D in RRMS is warranted to more assess the efficacy of this intervention Objective To assess whether three novel interventions , formulated based on a systems medicine therapeutic concept , reduced disease activity in patients with relapsing – remitting multiple sclerosis ( MS ) who were either treated or not with disease-modifying treatment . Design A 30-month r and omised , double-blind , placebo-controlled , parallel design , phase II proof-of-concept clinical study . Setting s Cyprus Institute of Neurology and Genetics . Participants 80 participants were r and omised into four groups of 20 each . A total of 41 ( 51 % ) patients completed the 30-month trial . The eligibility criteria were an age of 18–65 ; a diagnosis of relapsing – remitting MS according to the McDonald criteria ; a score of 0.0–5.5 on the Exp and ed Disability Status Scale ( EDSS ) ; MRI showing lesions consistent with MS ; at least one documented clinical relapse and either receiving or not a disease-modifying treatment within the 24-month period before enrolment in the study . Patients were excluded because of a recent ( < 30 days ) relapse , prior immunosuppressant or monoclonal antibody therapy , pregnancy or nursing , other severe disease compromising organ function , progressive MS , history of recent drug or alcohol abuse , use of any additional food supplements , vitamins or any form of polyunsaturated fatty acids , and a history of severe allergic or anaphylactic reactions or known specific nutritional hypersensitivity . Interventions The first intervention ( A ) was composed of Ω-3 and Ω-6 polyunsaturated fatty acids at 1:1 wt/wt . Specifically , the Ω-3 fatty acids were docosahexaenoic acid and eicosapentaenoic acid at 3:1 wt/wt , and the Ω-6 fatty acids were linoleic acid and γ-linolenic acid at 2:1 wt/wt . This intervention also included minor quantities of other specific polyunsaturated , monounsaturated and saturated fatty acids as well as vitamin A and vitamin E ( α-tocopherol ) . The second intervention ( B , PLP10 ) was a combination of A and γ-tocopherol . The third intervention ( C ) was γ-tocopherol alone . The fourth group of 20 participants received placebo . The interventions were administered per os ( by mouth ) once daily , 30 min before dinner for 30 months . Main outcome measures The primary end point was the annualised relapse rate ( ARR ) of the three interventions versus the placebo at 2 years . The secondary end point was the time to confirmed disability progression at 2 years . Results A total of 41 ( 51 % ) patients completed the 30-month trial . Overall , for the per- protocol analysis of the 2-year primary end point , eight relapses were recorded in the PLP10 group ( n=10 ; 0.40 ARR ) versus 25 relapses in the placebo group ( n=12 ; 1.04 ARR ) , representing a 64 % adjusted relative rate reduction for the PLP10 group ( RRR 0.36 , 95 % CI 0.15 to 0.87 , p=0.024 ) . In a subgroup analysis that excluded patients on monoclonal antibody ( natalizumab ) treatment , the observed adjusted RRR became stronger ( 72 % ) over the 2 years ( RRR 0.28 , 95 % CI 0.10 to 0.79 , p=0.016 ) . The per- protocol analysis for the secondary outcome at 2 years , the time to disability progression , was significantly longer only for PLP10 . The cumulative probability of disability progression at 2 years was 10 % in the PLP10 group and 58 % in the placebo group ( unadjusted log-rank p=0.019 ) . In a subgroup analysis that excluded patients on natalizumab , the cumulative probability of progression was 10 % for the 10 patients in the PLP10 group and 70 % for the 12 patients in the placebo group , representing a relative 86 % decrease in the risk of the sustained progression of disability in the PLP10 group ( unadjusted log-rank p=0.006 ; adjusted HR , 0.11 ; 95 % CI 0.01 to 0.97 , p=0.047 ) . No adverse events were reported . Interventions A ( 10 patients ) and C ( 9 patients ) showed no significant efficacy . Conclusions In this small proof-of-concept , r and omised , double-blind clinical trial ; the PLP10 treatment significantly reduced the ARR and the risk of sustained disability progression without any reported serious adverse events . Larger studies are needed to further assess the safety and efficacy of PLP10 . Trial registration International St and ard R and omised Controlled Trial , number IS RCT N87818535 Studies of linoleic acid levels in the blood of patients with multiple sclerosis ( MS ) have suggested that these levels drop during acute exacerbations . 1 This prompted Millar et al 2 to undertake a double-blind study of the effects of linoleic acid administration on the course of MS . The trial was conducted in two independent centers ( London and Belfast ) . Seventy-five patients were studied in a doubleblind protocol . Clinical scoring employed the Kurtzke disability status scale 3 and a method for scoring severity of relapses . 2 At the end of the trial , the latter showed a significant reduction in both numbers and severity of relapses in the linoleic acid-treated group . No long-term beneficial effects were detected . My colleagues and I attempted to confirm these observations , using timed studies of functional ability , the Kurtzke disability status scale , and the Kurtzke functional scales as measures of neurologic involvement . PATIENTS AND METHODS Patients One hundred and sixteen patients with acute remitting multiple sclerosis ( MS ) took part in a double-blind controlled trial of treatment with polyunsaturated fatty acids and were r and omly allocated to one of four groups . Two groups received linoleic acid , one alone as a spread and one with gamma-linolenic acid in capsules ( Naudicelle ) ; and two control groups received oleic acid , one as a spread and one in capsules . Rates of clinical deterioration and frequencies of attacks were not significantly different between treated and control groups . Exacerbations were shorter and less severe in patients receiving a high dose of linoleic acid than in controls , but those receiving a lower dose -- that is , Naudicelle -- showed no such difference . Thus supplementing the diet with 20 g linoleic acid marginally affected the duration and severity of relapses of MS but had no effect on overall disability . The dose of Naudicelle used provided insufficient supplementation OBJECTIVE To investigate whether ω-3 fatty acids reduce magnetic resonance imaging ( MRI ) and clinical disease activity in patients with multiple sclerosis , both as monotherapy and in combination with interferon beta-1a treatment . DESIGN Multicenter , r and omized , double-blind , placebo-controlled clinical trial conducted from 2004 to 2008 . SETTING Thirteen public neurology departments in Norway . PARTICIPANTS Patients aged 18 to 55 years with active relapsing-remitting multiple sclerosis , with a disability score equivalent to 5.0 or less on the Kurtzke Exp and ed Disability Status Scale . Ninety-two patients were r and omized to ω-3 fatty acids ( n = 46 ) or placebo capsules ( n = 46 ) . INTERVENTIONS Administration of 1350 mg of eicosapentaenoic acid and 850 mg of docosahexaenoic acid daily or placebo . After 6 months , all patients in addition received subcutaneously 44 μg of interferon beta-1a 3 times per week for another 18 months . MAIN OUTCOME MEASURE The primary outcome measure was MRI disease activity as measured by the number of new T1-weighted gadolinium-enhancing lesions during the first 6 months . Secondary outcome measures included MRI disease activity after 9 months and 24 months , relapse rate , disability progression , fatigue , quality of life , and safety . RESULTS The cumulative number of gadolinium-enhancing MRI lesions during the first 6 months were similar in the ω-3 fatty acids and placebo groups ( median difference , 1 ; 95 % CI , 0 to 3 ; P = .09 ) . No difference in relapse rate was detected after 6 ( median difference , 0 ; 95 % CI , 0 to 0 ; P = .54 ) or 24 ( median difference , 0 ; 95 % CI , 0 to 0 ; P = .72 ) months . The proportion of patients without disability progression was 70 % in both groups ( P > .99 ) . No differences were detected in fatigue or quality -of-life scores , and no safety concerns appeared . Serum analyses of fatty acids showed an increase in ω-3 fatty acids ( mean difference , 7.60 ; 95 % CI , 5.57 to 7.91 ; P < .001 ) in the patients treated with ω-3 fatty acids compared with the placebo group . CONCLUSION No beneficial effects on disease activity were detected from ω-3 fatty acids when compared with placebo as monotherapy or in combination with interferon beta-1a . Magnetic resonance imaging disease activity was reduced as expected by interferon beta-1a . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00360906 A trial of n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis has been conducted over a 5 year period . Ambulant patients ( 312 ) with acute remitting disease were r and omly allocated to treatment or placebo . Both groups were given dietary advice to increase the intake of n-6 polyunsaturated fatty acids and the treatment group in addition received capsules containing n-3 polyunsaturated fatty acids . Analysis of clinical outcome at the end of 2 years of treatment was made in terms of the duration , frequency and severity of relapses and the number of patients who had improved or remained unchanged . The results showed no significant difference at the usual 95 % confidence limits but there was a trend in favour of the group treated with n-3 polyunsaturated fatty acids in all parameters examined Background : High vitamin D levels may reduce the risk of relapses and disease progression in multiple sclerosis . Methods : This 96-week r and omised controlled trial was design ed to assess the effect of vitamin D3 supplementation on bone mineral density in persons with multiple sclerosis . Supplementation with 20,000 IU vitamin D3 weekly raised median serum 25-hydroxy vitamin D ( 25[OH]D ) to 121 nmol/L. The modified intention to treat analysis included 35 persons in the vitamin D3 group and 33 in the placebo group . Participants were age 21 to 50 years and fully ambulatory ( median Exp and ed Disability Status Scale ( EDSS ) 2.5 ) . We studied the effect of supplementing vitamin D3 on the exploratory outcomes annualised relapse rate ( ARR ) , EDSS , multiple sclerosis functional composite ( MSFC ) components , grip strength , and fatigue . Results : After 96 weeks , there was no significant difference between groups in ARR ( absolute difference 0.10 , 95 % CI -0.07 to 0.27 ; p = 0.25 ) , EDSS ( absolute difference -0.01 , 95 % CI -0.35 to 0.35 ; p = 0.97 ) , MSFC components , grip strength , or fatigue . Conclusion : Supplementation with 20,000 IU vitamin D3 weekly did not result in beneficial effects on the measured multiple sclerosis-related outcomes . This study was not powered to address clinical outcomes , but none of the results were suggestive of an effect in this unselected population of fully ambulatory persons with multiple sclerosis |
13,594 | 30,627,791 | There was no difference in pooled estimates of corrected or uncorrected distance vision between multifocal and st and ard IOLs .
Newer multifocal lenses had statistically significantly better outcomes than older diffractive lenses or refractive lenses , when compared to monofocal IOLs , in near vision , quality of vision , and risk of halos .
Conclusions Multifocal IOLs compared to st and ard IOLs or monovision result in better uncorrected near vision and a higher proportion of patients who achieve spectacle independence , but greater risk of unwanted visual phenomena .
Newer diffractive lenses may be better than refractive lenses in near vision and quality of vision outcomes , with less risk of halos than older diffractive lenses and refractive lenses . ( | Purpose Multifocal intraocular lenses ( IOLs ) offer the possibility of spectacle-free vision following cataract surgery compared to st and ard IOLs .
Existing systematic review s have generally concluded that multifocal IOLs result in better uncorrected near vision and greater spectacle independence , but more unwanted visual phenomena such as glare and halos , compared to monofocal IOLs .
However , the certainty of evidence has been low for most outcomes , and pooled analyses have grouped together technologically obsolete lenses with newer lenses , potentially obscuring differences in performance across different lens types . | OBJECTIVE Two million cataract extraction s are performed annually in the United States . The procedure is nearly always accompanied by implantation of a monofocal intraocular lens ( IOL ) , which corrects the patient 's distance vision . The authors ' objective was to measure visual function and quality -of-life outcomes associated with bilateral implantation of a multifocal IOL , which corrects distance and near vision , and to compare the outcomes with those of the st and ard therapy . DESIGN A prospect i ve , r and omized , double-masked , clinical trial was conducted at eight sites in the United States , seven sites in Germany , and one site in Austria . PARTICIPANTS Participants included 245 cataract patients , 127 of whom received the multifocal IOL bilaterally and 118 of whom received a monofocal IOL of nearly identical construction bilaterally . METHODS Clinical data included visual acuity ( VA ) , complications , and adverse events . Quality -of-life data were collected using a previously vali date d survey instrument at baseline , after first eye surgery , and after second eye surgery . RESULTS At 3 months after surgery , patients who had received multifocal IOLs had significantly better uncorrected and distance corrected binocular near VA compared with patients who had received monofocal IOLs ( mean uncorrected VA , 20/26 multifocal vs. 20/40 monofocal ; mean distance corrected VA , 20/28 multifocal vs. 20/45 monofocal ; P < 0.0001 ) . Additionally , 96 % of patients who had received multifocal IOLs and 65 % of patients who had received monofocal IOLs achieved both 20/40 and J3 ( Jaeger ) or better uncorrected , binocular distance and near visual acuities ( P < 0 . 0001 ) . Patients who had received multifocal IOLs were more likely than patients who had received monofocal IOLs to never wear glasses overall ( 32 % multifocal vs. 8 % monofocal ; P < 0.0001 ) . On a 4-point scale , patients who had received multifocal IOLs on average reported having between " a little bit " and " some " glare or halo , whereas patients who had received monofocal IOLs reported between " none " and " a little bit " of glare or halo ( 1.57 vs. 0.43 ; P < 0.001 ) . Patients who had received multifocal IOLs rated their vision without glasses better overall at near and at intermediate distances ( P < or = 0.002 ) and demonstrated better visual function for near tasks and social activities . CONCLUSIONS Cataract patients who received multifocal IOLs at time of surgery obtained better uncorrected and distance corrected near VA and reported better overall vision , less limitation in visual function , less spectacle dependency , and more glare or halo than those who received traditional monofocal IOLs Aims To evaluate the functional effect of bilateral implantation of two different multifocal intraocular lenses ( IOL ) compared with the st and ard monofocal IOL . Methods Sixty-nine patients were recruited into a prospect i ve , double-masked , r and omised , controlled trial at a single hospital in the United Kingdom . Sixty completed follow-up ; 16 implanted with monofocal IOLs , 29 with AMO ’ ARRAY ’ multifocal IOLs and 15 with Storz ’ TRUEVISTA ’ bifocal IOLs . Phacoemulsification and IOL implantation was performed to a st and ardised technique in both eyes within a 2-month period . The main outcome measures were distance and near visual acuity , depth of field and vali date d assessment of subjective function ( TyPE question naire ) . Results Unaided distance acuity was good , and equivalent across the three groups . Corrected distance acuity was significantly lower in the bifocal group . Patients with multifocal and bifocal IOLs could read smaller absolute print size than those in the monofocal group ( P = 0.05 ) , but at a closer reading distance such that mean unaided near acuity was equal in the three groups . Corrected near acuity was significantly higher in the monofocal control group ( P < 0.05 ) . Depth of field was increased in multifocal ( P = 0.06 ) and bifocal ( P = 0.004 ) groups . Overall visual satisfaction was equal in the three groups , while near visual satisfaction was higher in the multifocal group than the monofocal ( P = 0.04 ) . Spectacle independence was not seen in the monofocal group , but was achieved in 28 % of multifocal IOL patients and 33 % of bifocal patients ( P < 0.001 ) . Adverse symptoms such as glare and haloes were significantly more bothersome with multifocal ( not bifocal ) IOLs than monofocals ( P = 0.01 ) . Conclusions Multifocal and bifocal IOLs improved unaided near vision performance , with around one in three patients becoming spectacle-independent . The main adverse effect was an increased incidence of subjective glare and haloes in the multifocal IOL group Purpose : To compare contrast sensitivity ( CS ) after implantation of a diffractive bifocal intraocular lens ( IOL ) and a monofocal IOL of similar design . Setting : Seven European centers . Methods : In this r and omized , prospect i ve study , CS was tested 5 months after cataract and IOL implantation surgery in 115 patients with a diffractive bifocal IOL and 106 patients with a monofocal IOL . It was also tested in a subgroup of 38 patients who had bilateral implantation of a diffractive bifocal IOL . Contrast sensitivity was tested using the Vision Contrast Test System ( VCTS ) . Results : In patients with a best corrected visual acuity ( BCVA ) of 1.0 or better , the CS at all spatial frequencies ( 1.5 to 18 cycles/degree ) , both at distance and near , was slightly lower in the bifocal IOL group than in the monofocal group . Mean values were within the normal range . In patients with a BCVA of less than 1.0 , the CS was lower and the difference between the bifocal and monofocal groups was less . In patients with bilateral bifocal IOLs , CS was better when tested bilaterally than when testing the better eye alone . Pupil size affected the results to a small degree . Contrast sensitivity appeared to improve over time after implantation of a diffractive bifocal IOL . Conclusions : In patients with cataract and no other eye pathology , the diffractive bifocal IOL will slightly reduce the CS at all spatial frequencies . In those with reduced visual acuity after cataract surgery , CS will be reduced accordingly . In this situation , the reduction from the diffractive bifocal optic would be minor 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 : To compare changes in reading performance parameters after implantation of 4 multifocal intraocular lens ( IOL ) models and a monofocal IOL . SETTING : Department of Ophthalmology , Paracelsus Medical University , Salzburg , Austria . DESIGN : Prospect i ve r and omized controlled clinical trial . METHODS : Patients with bilateral cataract without additional ocular pathology were scheduled for bilateral implantation of Acri . Smart 48S monofocal , Acrysof Restor SN6AD3 apodized multifocal , AT LISA 366D diffractive multifocal , Tecnis ZMA00 diffractive multifocal , or Rezoom refractive multifocal IOLs . Bilateral corrected and uncorrected reading acuity , reading distance , mean and maximum reading speeds , and smallest log‐scaled print size of a Radner reading chart were evaluated under bright lighting conditions ( 500 lux ) using the Salzburg Reading Desk . Pupil size was not measured throughout the trial . The minimum follow‐up was 12 months . RESULTS : The diffractive multifocal groups had significantly better uncorrected reading acuity and uncorrected smallest print size than the monofocal and refractive multifocal groups 1 , 6 , and 12 months postoperatively . The diffractive IOL groups had comparable uncorrected reading distance of approximately 32 cm , which was larger in the monofocal group ( 38.9 ± 8.4 cm ) and refractive multifocal group ( 37.1 ± 7.3 cm ) at the last visit . Patients with diffractive IOLs could read print sizes of approximately 0.74 to 0.87 mm , which was much better than in the monofocal and refractive multifocal groups . The diffractive AT LISA IOL provided the best reading speed values ( mean and maximum , corrected and uncorrected ) . CONCLUSION : Multifocal IOLs with a diffractive component provided good reading performance that was significantly better than that obtained with a refractive multifocal or monofocal IOL . Financial Disclosure : Drs . Grabner and Dexl were patent owners of the Salzburg Reading Desk technology ( now owned by SRD‐Vision , LLC ) . No other author has a financial or proprietary interest in any material or method mentioned PURPOSE To compare new-generation multifocal intraocular lenses ( IOLs ) with monofocal IOLs . DESIGN R and omized prospect i ve clinical trial . PARTICIPANTS Sixty-two consecutive patients with cataract , seen between January of 2005 and January of 2006 at the Department of Ophthalmology of Palermo University Hospital in Italy , were bilaterally implanted with monofocal ( AR 40 , Advanced Medical Optics [ AMO ] , Santa Ana , CA ; 15 patients ) , multifocal refractive ( Array SA40N , AMO ; 16 patients ) , multifocal refractive ( ReZoom , AMO ; 15 patients ) , or multifocal diffractive pupil-independent ( Tecnis ZM900 , AMO ; 16 patients ) IOLs . INTERVENTION Bimanual phacoemulsification . MAIN OUTCOME MEASURES Primary outcomes were far , near , and intermediate visual acuity of the 4 IOL-implanted groups . Secondary outcomes were defocusing curves , contrast sensitivity , patients ' quality of life ( 7-item visual function question naire [ VF-7 ] , halos and glare presence , overall satisfaction ) , and spectacle independence . Snellen visual acuity was measured as uncorrected visual acuity ( UCVA ) , best corrected visual acuity ( BCVA ) , uncorrected near visual acuity ( UCNVA ) , best distance corrected near visual acuity ( BDCNVA ) , best corrected near visual acuity ( BCNVA ) , uncorrected intermediate visual acuity ( UCIVA ) , and best distance corrected intermediate visual acuity ( BDCIVA ) . RESULTS UCNVA was 20/50 in the monofocal IOL group , compared with 20/32 or better in the multifocal IOL groups ( P<0.0005 ) . The monofocal IOL group exhibited a lower BDCNVA than the multifocal IOL groups ( P<0.0005 ) . The diffractive multifocal IOL group performed better than either refractive group ( P = 0.007 ) . UCIVA was significantly different ( P = 0.001 ) among the groups : monofocal ( AR 40 ) 20/32 ; multifocal refractive ( Array SA40N ) 20/30 ; multifocal refractive ( ReZoom ) 20/25 ; and multifocal diffractive ( Tecnis ZM900 ) 20/30 . Defocusing curves with -3.00 diopter lens exhibited a better trend in the diffractive group . The refractive multifocal IOL groups exhibited lower contrast sensitivities at 3 cycles/degree ( P = 0.038 ) . The VF-7 mean score was significantly lower in the monofocal than the multifocal IOL groups ( P = 0.002 ) . Night halos were more common in the refractive groups ( P<0.01 ) . Spectacle independence was 20 % in the monofocal IOL group , 43.7 % and 53.3 % in the refractive multifocal IOL groups , and 87.5 % in the diffractive multifocal IOL group ( P<0.05 ) . CONCLUSIONS Multifocal IOLs provide a greater depth of focus and higher patient satisfaction , and make intermediate and near visual tasks easier than do monofocal lenses . New-generation , diffractive , pupil-independent multifocal IOLs provide better near vision , equivalent intermediate vision , less unwanted photic phenomena , and greater spectacle independence than either monofocal or refractive multifocal IOLs OBJECTIVE To compare the binocular near vision performance in patients implanted with the 1CU accommodating intraocular lens ( IOL ) with a multifocal and monofocal IOL . DESIGN Prospect i ve , r and omized , double-masked clinical trial . PARTICIPANTS Ninety patients presenting for cataract surgery to the Department of Ophthalmology , Hillingdon Hospital were r and omized to receive the 1CU accommodative IOL , a multifocal IOL , or a monofocal IOL ( control group ) . METHODS Patients underwent bilateral sequential phacoemulsification with implantation of 1 of the 3 IOL types and were assessed at 3 and 18 months after second-eye surgery . MAIN OUTCOME MEASURES Logarithm of the minimum angle of resolution distance and near visual acuities ( VAs ) ( unaided and distance corrected ) , contrast sensitivity , and accommodative amplitude ( near point and defocusing ) were measured at 3 and 18 months . Reading speed was assessed at 18 months , and glare symptoms and spectacle independence were compared using a st and ardized question naire . RESULTS Mean unaided and distance-corrected binocular near VAs were similar in the 1CU and multifocal and were significantly higher than the control group 's ( P<0.02 ) . There was no significant difference in reading speed between any of the groups , but critical print sizes were similar in the 1CU and multifocal groups and significantly better than the control group 's ( P = 0.02 ) . The accommodative range was highest in the multifocal group and lowest in the control group , and there was no significant difference between the 1CU and control groups for defocus or near point at 18 months . Of the 1CU group and control group , 71.4 % and 63.2 % , respectively , experienced no glare at 18 months , compared with only 25 % of the multifocal group ( P = 0.01 ) . Of the 1CU group and multifocal group , 19 % and 27.3 % , respectively , were completely spectacle independent at 18 months ; none of the control group was ( P = 0.05 ) . CONCLUSIONS The 1CU accommodating IOL provides improved near vision compared with a monofocal IOL . There is a discrepancy between the near function and accommodative amplitude measured in the 1CU . The multifocal provides excellent near acuity , but photopic phenomena remain a problem inherent in the lens design The aim of this study was to compare the visual performance of Acrysof ReSTOR and Acrysof Natural intraocular lenses ( IOLs ) following cataract surgery . A r and omized prospect i ve study was performed in which 64 eyes ( 51 patients ) were divided r and omly into two groups . Monofocal IOLs ( Acrysof Natural ) were implanted into 34 eyes ( 27 patients ) and multifocal IOLs ( Acrysof ReSTOR ) were implanted into 30 eyes ( 24 patients ) using phacoemulsification surgery . The corrected distance visual acuity , near visual acuity , pseudoaccommodation , contrast sensitivity ( CS ) and wavefront analysis were measured at 1 week , 1 month and 3 months after surgery . The distance vision of the monofocal and ReSTOR patients improved equally with glasses ( P<0.05 ) . A greater improvement in near vision without glasses was observed in the ReSTOR-implanted patients ( P<0.01 ) . The CS values of the multifocal IOL group were significantly lower than those of the monofocal IOL group for all spatial frequencies tested ( P<0.05 ) . The spherical aberration was significantly higher in the multifocal IOL group compared with the monofocal IOL group ( P<0.05 ) . We observed no differences in coma between the two groups . The difference in the amplitude of pseudoaccommodation between the two groups was statistically significant ( −3.14±0.91 D in the ReSTOR group vs. −1.03±0.33 D in the Natural group , P<0.01 ) . The improvement in near vision was significantly more evident in the ReSTOR patients . Compared with the monofocal IOL lens , the multifocal lens is able to increase the amplitude of pseudoaccommodation . However , increased spherical aberration may contribute to lower CS values in the multifocal IOL group PURPOSE To evaluate selected functional and physical properties of 2 models of accommodative intraocular lenses ( IOLs ) compared with those of a st and ard monofocal IOL . DESIGN Prospect i ve r and omized comparative trial . PARTICIPANTS Subjects were divided into 3 groups . In group 1 , 30 eyes ( 19 subjects ) received 1CU IOL implantation ; in group 2 , 29 eyes ( 19 subjects ) received AT-45 IOL implantation ; and in group 3 , 21 eyes ( 21 subjects ) were implanted with a monofocal IOL as a control . INTERVENTION Cataract surgery with implantation of the 1CU and AT-45 accommodative IOL models in the study groups , and the ACR6D monofocal IOL in the control group . MAIN OUTCOME MEASURES Far and near distance visual parameters were assessed at 1 , 6 , and 12 months after surgery in the accommodative IOL groups , and at 1 and 12 months in the control group . Anterior segment anatomy was investigated by ultrasound biomicroscopy , with and without visual accommodative stimulation . RESULTS The accommodative IOL groups significantly differed from the controls in terms of lower near-distance refractive addition ( NDRA ) and better distance-corrected near visual acuity ( DCNVA ) , with P<0.001 at 1 year . The anterior IOL displacement during accommodation ( DeltaACD ) was significantly larger in the study groups , and this correlated with DCNVA . Until 6 months , the DeltaACD correlated with the solicited sclerociliary process rotation only in the study groups . CONCLUSION This 12-month study demonstrated that the accommodating IOLs achieved better clinical results than the monofocal IOL in terms of DCNVA and NDRA . These results support the hypothesis that accommodative IOLs proportionally react to ciliary body rotation , although this relationship became less evident at 12 months ABSTRACT A prospect i ve trial was set up to compare pseudoaccommodation . Fifty patients were r and omized into two groups . Group 1 comprised 25 patients who had a monofocal implant and a postoperative refractive aim of ‐0.3 to ‐1.3 diopter ( D ) spherical equivalent and an astigmatic component between 1.0 and 1.75 D cylinder . Group 2 comprised 25 patients who had a new multizone refraction style multifocal implant and a postoperative refractive aim of ‐0.5 to + 0.5 D spherical equivalent and an astigmatic component of less than 1.0 D cylinder . Eighty percent of postoperative refractions in Group 1 and 88 % in Group 2 were within 0.5 D either side of the refractive aim . Forty‐eight percent of Group 1 and 72 % of Group 2 could see both 20/40 and J3 unaided . Four percent of Group 1 and 84 % of Group 2 could read J2 with the distance correction . Sixteen percent of Group 1 and 48 % of Group 2 could read J2 at 25 cm unaided ( P = .03 ) . Sixty‐four percent of Group 1 and 88 % of Group 2 stated they could manage daily activities without glasses . However , 88 % of Group 1 and 52 % of Group 2 requested reading glasses to improve clarity of the smallest print ABSTRACT In a unilateral prospect i ve clinical trial , 77 cases were r and omized to receive a 3 M multifocal IOL or a conventional monofocal implant . Multifocal cases had better uncorrected near vision than monofocal cases at the two to four month visit . Thirty percent of the multifocal cases had near acuity J1 , while only 4 % of the monofocal cases had that acuity . Eighty‐seven percent of multifocal cases and 71 % of monofocal cases had near acuities of J1 to J3 . With distance correction in place , 54 % of multifocal cases had near acuities of J1 to J2 , while only 28 % of monofocal cases had comparable acuities ( P = .04 ) . There have been no serious postoperative complications in either group BACKGROUND Laboratoires Domilens , Lyon , France , has introduced a new aspheric multifocal intraocular lens ( IOL ) , the Progress 3 . The central portion , measuring 4.7 mm in diameter , has an anterior surface of progressively increasing power , such that there is a central add of + 5.00 dioptres . We compared contrast sensitivity and depth of focus in patients who received the Progress 3 and in those who received a conventional monofocal IOL . METHODS Prospect i ve study . Forty patients with age-related cataract were r and omly divided into two groups : 20 patients received the Progress 3 aspheric multifocal IOL , and 20 patients received a conventional monofocal IOL of similar design . Contrast sensitivity was measured with the Pelli-Robson letter-based chart . Depth of focus was determined by dialling a series of overcorrections over the patient 's manifest refraction until the patient read 6/12 clearly . The depth of focus was defined as the range over which 6/12 or better acuity was achieved . Quality of vision was evaluated by patient question naire . RESULTS Mean contrast sensitivity was significantly lower in the patients with a multifocal IOL than in those with a monofocal IOL ( 1.38 vs. 1.56 log units ) ( p < 0.001 ) . The mean depth of focus values for the two groups were 3.10 D and 1.65 D respectively ( p < 0.001 ) . The prevalence of subjective problems was similar in the two groups . INTERPRETATION In our opinion , aspheric multifocal IOLs should be reserved for patients who are willing to trade increased depth of focus for reduced contrast sensitivity postoperatively PURPOSE Although monofocal intraocular lenses ( IOLs ) are effective in improving vision after cataract surgery , the loss of accommodation is not restored by implantation of these IOLs . Because multifocal IOLs may improve uncorrected distance and near vision , we compared the clinical outcome and patient satisfaction after implantation of monofocal and multifocal IOLs . Sociodemographics , eagerness for spectacle independence ( ESI ) , and neuroticism were tested as predictors of satisfaction . DESIGN R and omized controlled trial . PARTICIPANTS Cataract patients with no ocular comorbidity were operated from August 1999 to January 2001 ; 75 patients were implanted with monofocal IOLs , and 78 with multifocal IOLs . METHODS Assessment s were made preoperatively ( t1 ) , 3 months after first-eye surgery ( t2 ) , and 3 months after second-eye surgery ( t3 ) . Primary outcomes were obtained by ophthalmic tests , whereas secondary outcomes were examined by interviews . MAIN OUTCOME MEASURES Primary outcomes consisted of near and distance visual acuity ( VA ) . Secondary outcomes related to spectacle dependence , vision-related functioning , and patient satisfaction . RESULTS At t3 , multifocal IOLs showed significantly better uncorrected near VA than monofocal IOLs ( P<0.01 ) and an increase in quality ratings of unaided near vision between t1 and t3 ( on a scale of 1 - 5 : 1.6 at t1 vs. 2.9 at t3 , P<0.001 ) . At t2 and t3 , patients with multifocal IOLs were more likely to " never " or " only now and then " wear spectacles for near and distance than patients with monofocal IOLs ( at t3 , 42.7 % multifocal vs. 21.6 % monofocal for near [ P = 0.002 ] and 75.0 % multifocal vs. 46.2 % monofocal for distance [ P = 0.001 ] ) . On a 0- to 15-point scale , monofocal IOL patients showed fewer complaints from cataract symptoms , including halos and distorted vision , at t3 ( 1.2 monofocal vs. 2.1 multifocal [ P = 0.002 ] ) . Satisfaction related to preoperative expectations was similar in the monofocal and multifocal groups . The perceived quality of corrected near vision had the strongest relationship with patient satisfaction ( beta = 0.22 ; 95 % confidence interval : 0.060 - 0.523 ) . Sociodemographics , ESI , and neuroticism did not predict patient satisfaction . CONCLUSIONS Overall , patient satisfaction did not differ between the groups of monofocal and multifocal IOLs . Independent of ESI or neuroticism scores , success of both IOLs depends on preoperative expectations and postoperative quality of aided near vision . This article contains additional online-only material available at Purpose : To evaluate safety and efficacy of Array ® SA40N multifocal intraocular lens ( IOL ) ( AMO ) implantation in cataract surgery . Setting : Helsinki University Eye Hospital , Helsinki , Finl and . Methods : In this prospect i ve r and omized comparative trial , 80 patients scheduled for cataract surgery were selected based on preoperative counseling and r and omized to have multifocal or monofocal IOL implantation . Fifty‐three eyes of 35 patients received a multifocal IOL and 67 eyes of 40 patients , a monofocal IOL . The incidence of complications and visual outcome in the multifocal and monofocal IOL groups were compared . Quality of vision was measured by comparing the severity of visual symptoms ( glare , halos , and cataract symptoms score ) , changes in functional impairment measured by a 7‐item visual function test ( VF‐7 ) , changes in global measures of vision ( trouble and satisfaction with vision ) , and range of accommodation and contrast sensitivity . Results : Intraoperative and postoperative complications and adverse events were few and required no further surgical intervention . Both distance and near visual acuities were significantly better in the multifocal group than in the monofocal group ; the difference was most prominent in distance corrected near acuity ( P<.001 ) . Thirty‐five eyes ( 67.3 % ) in the multifocal group and 10 eyes ( 14.9 % ) in the monofocal group achieved a distance corrected near acuity of J6 ( 20/40 ) or better ; 30 eyes ( 56.6 % ) and 19 eyes ( 28.4 % ) , respectively , achieved a best corrected distance acuity of 20/20 or better . Glare symptoms decreased postoperatively in both groups but were slightly more common in the multifocal group . In contrast , halos were significantly more common at 1 month in the multifocal group ( P<.001 ) . Contrast sensitivity values were slightly lower with multifocal IOLs at almost all spatial frequencies , but the difference was not significant . The change in the quality of life postoperatively , measured with the VF‐7 , was significant and identical in both groups . Conclusions : Pseudophakic eyes with multifocal IOLs had better distance and near acuity and range of accommodation than eyes with a monofocal IOL . Slightly lower contrast sensitivity and increased perception of halos by subjects with the multifocal IOL appear to be an acceptable compromise to enhanced near and distance vision INTRODUCTION Multifocal intraocular lenses ( IOLs ) have been design ed to provide improved near visual acuity without spectacles compared with monofocal IOLs . Early studies have reported variables amounts of decreased visual acuity and contrast sensitivity with multifocal IOLs , and some patients have experienced halos and glare . METHODS The authors performed a prospect i ve , double-masked , multicenter evaluation of 62 patients r and omized between a new zonal-progressive optic multifocal IOL and a monofocal IOL . RESULTS Mean postoperative spherical equivalent , astigmatism , and uncorrected and best-corrected distance visual acuity were similar between the two groups . Patients with a multifocal IOL achieved significantly better uncorrected near visual acuity than patients with monofocal IOLs ( J3 + versus J7 ; P less than 0.0001 ) . With distance correction only , mean near visual acuity was J2 versus J5- ( P = 0.0001 ) . Best-corrected near visual acuity was J1 for both groups , with 1.36 diopters ( D ) for the multifocal group versus 2.37 D for the monofocal group ( P less than 0.0001 ) . Regan contrast sensitivity was lower for the multifocal patients at all contrast levels , and achieved statistical significance at very low contrast ( 11 % contrast ; P = 0.0024 ) . Fifty-two percent of patients with a multifocal IOL reported that they did not need spectacles at all or used them only for their fellow eye , compared with 25 % of the patients with monofocal IOLs . CONCLUSION Both monofocal and multifocal implant patients were very satisfied with the results of their cataract extraction and IOL implant surgery . A small loss of contrast sensitivity with the multifocal IOL was demonstrated , consistent with theoretical predictions . The functional significance of the loss of contrast sensitivity appears to be small and counterbalanced by the advantage of improved uncorrected near visual acuity Purpose To compare the effect of monovision correction and multifocal intraocular lens ( IOL ) implantation on patient satisfaction , spectacle dependence , visual acuity , and dysphotopsia in cataract patients . Setting University Hospital of Alex and roupolis , Democritus University of Thrace , Alex and roupolis , Greece . Design Prospect i ve r and omized trial . Methods Patients with a diagnosis of senile cataract with stage 2 nuclear opalescence were r and omly assigned to 2 groups : monovision and multifocal IOL implantation . Uncorrected ( UDVA ) and corrected ( CDVA ) distance visual acuity , Visual Function Index‐14 ( VF‐14 ) scores , and spectacle dependence were assessed prior to surgery and 6 months postoperatively . Results The monovision group comprised 38 patients and the multifocal IOL implantation group , 37 patients . Both techniques provided excellent refractive outcomes in UDVA and VF‐14 scores ( all P < .01 ) . No significant intergroup differences were detected in VF‐14 scores at the final postoperative examination . The monovision group patients presented significantly more spectacle dependence for near vision but less glare . Conclusions Monovision and multifocal IOL implantation provided excellent refractive outcomes for distance vision . Multifocal IOL insertion was associated with less dependence on glasses overall but significantly more dysphotopsia . Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned OBJECTIVE To compare spectacle independence in patients r and omized to receive bilateral multifocal intraocular lenses ( IOLs ) or monofocal IOLs with the powers adjusted to produce monovision . DESIGN R and omized , multicenter clinical trial . PARTICIPANTS A total of 212 patients with bilateral , visually significant cataract . METHODS Before bilateral sequential cataract surgery , patients were r and omized ( allocation ratio 1:1 ) to receive bilateral Tecnis ZM900 diffractive multifocal lenses ( Abbott Medical Optics , Santa Ana , CA ) or Akreos AO monofocal lenses ( Bausch & Lomb , Rochester , NY ) with the powers adjusted to target -1.25 diopters ( D ) monovision . Outcomes were assessed 4 months after the second eye underwent operation . MAIN OUTCOME MEASURES The primary outcome was spectacle independence . Secondary outcomes included question naires ( VF-11R , dysphotopsia symptoms , and satisfaction ) and visual function measures ( near , intermediate , and distance logarithm of minimum angle of resolution [ logMAR ] visual acuity , stereoacuity , contrast sensitivity , and forward light scatter ) . RESULTS A total of 212 patients were r and omized , and 187 patients ( 88 % ) returned for assessment 4 months after surgery . Uniocular distance refractions in the monovision arm showed a mean spherical equivalent of + 0.075 D in the distance eye and -0.923 in the near eye . In the multifocal arm , the mean distance spherical equivalents were -0.279 D and -0.174 D in the right and left eyes , respectively . A total of 24 of 93 patients ( 25.8 % ) in the monovision arm and 67 of 94 patients ( 71.3 % ) in the multifocal arm reported never wearing glasses ( P<0.001 , Fisher exact test ) . The adjusted odds ratio of being spectacle free was 7.51 ( 95 % confidence interval , 3.89 - 14.47 ) . Binocular uncorrected acuities did not differ significantly for distance ( 0.058 logMAR for monovision vs. 0.076 for multifocal , P = 0.3774 ) but were significantly worse in the multifocal arm for intermediate acuity ( 0.149 vs. 0.221 , P = 0.0001 ) and in the monovision arm for near acuity ( 0.013 vs. -0.025 , P = 0.037 ) . In the first postoperative year , 6 patients ( 5.7 % ) in the multifocal arm underwent IOL exchange ( 4 had a bilateral and 2 had a unilateral exchange ) . No patients in the monovision arm underwent IOL exchange . CONCLUSIONS Patients r and omized to bilateral implantation with the diffractive multifocal Tecnis ZM900 were more likely to report being spectacle independent but also more likely to undergo IOL exchange than those r and omized to receive monofocal implants ( Akreos AO ) with the powers adjusted to give low monovision Purpose : To compare a Pharmacia diffractive bifocal intraocular lens ( IOL ) with a monofocal lens of the same design without the diffractive grating . Setting : . Multicenter study . Methods : This r and omized , prospect i ve study comprised 70 patients with a monofocal IOL and 79 with a diffractive bifocal IOL . Follow‐up was 5 to 6 months . Near and distance visual acuities , contrast sensitivity , patient satisfaction , and spectacle use were evaluated . Results : All patients achieved a best corrected visual acuity of 0.5 or better ; 80 % in the monofocal and 71 % in the bifocal group had a best corrected visual acuity of 1.0 or better . Without correction , 93 % of the bifocal and 9 % of the monofocal group could read J3 or better . With distance correction , 99 % and 4 % , respectively , could read J3 or better . Contrast sensitivity was slightly lower in the bifocal group at distance and near for all spatial frequencies . In the bifocal group , 46 % never used spectacles for near tasks . Overall satisfaction was rated good by 86 % of the monofocal and 85 % of the bifocal group . Conclusions : The diffractive bifocal IOL performed well at distance and near . Patients who no longer require spectacles will benefit significantly from a bifocal IOL , but many with a bifocal IOL in one eye will require spectacles for the fellow eye Abstract In a prospect i ve , r and omized clinical trial , 42 patients received a monofocal intraocular lens and 38 a multifocal lens after extracapsular cataract extraction . Patients were examined three , six , and 12 months after surgery . Uncorrected visual acuity was 20/40 or better in 57 % of monofocal and 58 % of multifocal patients ; 12 % and 52 % had near uncorrected visual acuity of J1 to J2 , respectively . Best corrected visual acuities were not significantly different . Forty‐eight percent of the multifocal and 8 % of the monofocal group did not require spectacle correction . On a patient satisfaction question naire , 60 % of all patients reported discomfort when using spectacles for near vision . Patients in the multifocal group were more satisfied with their near vision than those in the monofocal group . The difference in satisfaction was not significantly different although more multifocal patients reported visual phenomena ( e.g. , glare , halos ) . Mean contrast sensitivity for the monofocal group and the multifocal group was 1.73 and 1.70 , respectively . At low contrast sensitivities , the difference was not significant although the monofocal patients scored better |
13,595 | 31,179,035 | Conclusion A growing evidence base , mainly from high-income countries and with significant heterogeneity , suggests HPV self-sampling can increase cervical cancer screening uptake compared with st and ard of care , with a marginal effect on linkage to clinical assessment /treatment . | Introduction Human papillomavirus ( HPV ) self-sampling test kits may increase screening for and early detection of cervical cancer and reduce its burden globally . | Background : In Italy , cervical cancer screening programmes actively invite women aged 25–64 years . Programmes are hindered by low participation . Methods : A sample of non-responder women aged 35–64 years , belonging to three different programmes ( in Rome , Florence and Teramo ) , was r and omly split into four arms : two control groups received st and ard recall letters to perform either Pap-test ( first group ) or human papillomavirus ( HPV ) test ( second group ) at the clinic . A third arm was sent letters offering a self- sample r for HPV testing , to be requested by phone , whereas a fourth group was directly sent the self- sample rs home . Results : Compliance with st and ard recall was 13.9 % ( N619 ) . Offering HPV test at the clinic had a nonsignificant effect on compliance ( N616 , relative risk (RR)=1.08 ; 95 % CI=0.82–1.41 ) . Self- sample r at request had the poorest performance , 8.7 % ( N622 , RR=0.62 ; 95 % CI=0.45–0.86 ) , whereas direct mailing of the self- sample r registered the highest compliance : 19.6 % ( N616 , RR=1.41 ; 95 % CI=1.10–1.82 ) . This effect on compliance was observed only in urban areas , Florence and Rome ( N438 , RR=1.69 ; 95 % CI=1.24–2.30 ) , but not in Abruzzo ( N178 , RR=0.95 ; 95 % CI=0.61–1.50 ) , a prevalently rural area . Conclusions : Mailing self- sample rs to non-responders may increase compliance as compared with delivering st and ard recall letters . Nevertheless , effectiveness is context specific and the strategy costs should be carefully considered Cervical cancer is more common in the Somali immigrant population than the general population in the United States ( US ) . There are low rates of cervical cancer screening among Somali women . This study compares cervical cancer screening test completion rates for a home human papilloma virus ( HPV ) test and st and ard clinic Pap test . Sixty‐three Somali immigrant women aged 30–70 years who had not undergone cervical cancer screening within the past 3 years were r and omly assigned to a home HPV test group ( intervention ) or a clinic Pap test group ( control ) . Test completion rates were measured at 3 months . Univariate and multivariate logistic regression models were used to explore factors associated with test completion ( intention‐to‐treat analysis ) . Participants in the HPV test group were 14 times more likely to complete the test compared to those in the Pap test group ( P = 0.0002 ) . Women who reported having friends/family members to talk about cancer screening were approximately three times more likely to complete any screening test than those who did not ( P = 0.127 ) and participants who reported residing in the US longer were more likely to complete a screening test ( P = 0.011 ) . Future research should explore the potential of using the home‐based HPV test kits as an initial approach to cervical cancer screening . Impact : The use of a self‐sampling HPV kit has the potential to increase cervical cancer screening in under‐served communities in the US Background : A r and omised trial to ascertain whether women who do not attend for cervical screening are more likely to respond to the opportunity to collect a self- sample for human papillomavirus ( HPV ) testing , or to a further invitation to attend for cervical screening . Methods : The study was carried out in a Primary Care Trust ( PCT ) in London between June 2009 and December 2009 . In total , 3000 women were r and omly selected from persistent non-responders ( i.e. , who had not responded to at least two invitations to attend for screening ) . The women were r and omised on a 1 : 1 basis to either receive an HPV self-sampling kit or a further invitation to attend for cervical cytology . The main outcome measures were ( 1 ) percentage of women attending for cervical cytology compared with those returning a self- sample HPV test or attending for cytology subsequent to receiving the kit and ( 2 ) percentage of those testing positive for HPV who attended further investigation . Results : The total response in the self-sampling group for screening was 10.2 % . Of the 1500 women in the control group sent a further invitation for cervical screening , 4.5 % attended for cytology screening . This difference is highly statistically significant ( P<0.0001 ) . Of the 8 women who tested positive for HPV , 7 attended for a cervical smear and had a concurrent colposcopy . Three of these ( 43 % ) had high- grade disease ( defined as CIN 2 + ) , with one found to have an invasive cancer ( stage 1b ) and one CIN 3 . Conclusions : The value of this intervention relies on the detection of high- grade CIN and early stage cancer with a good prognosis . The relatively high yield of abnormalities found is consistent with that expected among a hard to reach and relatively high-risk group of women . Our study suggests that self-sampling could increase participation among non-responders in Engl and , but further work is needed to ascertain whether the low response rate seen here is likely to be representative of the rest of the country . Other studies are needed to investigate the response to self-sampling in different demographic and geographic setting Objectives The incidence of cervical cancer is up to 20-fold higher among First Nations women in Canada than the general population , probably due to lower participation in screening . Offering human papillomavirus ( HPV ) self-sampling in place of Papanicolaou ( Pap ) testing may eventually increase screening participation and reduce cervical cancer rates in this population . Design A community-r and omised controlled screening trial . Setting First Nations communities in Northwest Ontario , Canada . Participants Women aged between 25 and 69 , living in Robinson Superior Treaty First Nations . The community was the unit of r and omisation . Interventions Women were asked to complete a question naire and have screening by HPV self-sampling ( arm A ) or Pap testing ( arm B ) . Primary outcome measures The number of women who participated in cervical screening . R and omisation Community clusters were r and omised to include approximately equivalent numbers of women in each arm . Results 6 communities were r and omised to arm A and 5 to arm B. One community withdrew , leaving 5 communities in each group ( 834 eligible women ) . Participation was < 25 % . Using clustered intention-to-treat ( ITT ) analysis , initial and cumulative averaged uptakes in arm A were 1.4-fold ( 20 % vs 14.3 % , p=0.628 ) and 1.3-fold ( 20.6 % vs 16 % , p=0.694 ) higher compared to arm B , respectively . Corresponding per protocol ( PP ) analysis indicates 2.2-fold ( 22.9 % vs 10.6 % , p=0.305 ) and 1.6-fold ( 22.9 % vs 14.1 % , p=0.448 ) higher uptakes in arm A compared to arm B. Screening uptake varied between communities ( range 0–62.1 % ) . Among women who completed a question naire ( 18.3 % in arm A , 21.7 % in arm B ) , the screening uptake was 1.8-fold ( ITT ; p=0.1132 ) or 3-fold ( PP ; p<0.01 ) higher in arm A versus arm B. Conclusions Pap and HPV self-sampling were compared in a marginalised , Canadian population . Results indicated a preference for self-sampling . More research on how to reach underscreened Indigenous women is necessary . Trial registration number IS RCT N84617261 Background Cervical cancer screening participation remains insufficient in most countries . Our aim was to evaluate whether offering a HPV self-sampling kit , either mailed directly to the woman ’s home or using timely opt-in procedures for ordering the kit , increased screening participation compared with a st and ard second reminder . Methods In this r and omized , controlled effectiveness trial , 9791 Danish women aged 30–64 who were due to receive the second reminder were equally r and omized to either : 1 ) direct mailing of a second reminder and a self-sampling kit ( directly mailed group ) ; 2 ) mailing of a second reminder that offered a self-sampling kit to be ordered by e-mail , text message , phone , or webpage ( opt-in group ) ; or 3 ) mailing of a second reminder to attend regular cytology screening ( control group ) . In an intention-to-treat analysis , we estimated the participation rate at 180 days post intervention , by returning a self- sample or attending regular cytology screening . We calculated the proportion of women with a positive HPV self- sample who attended for cervical cytology triage at the general practitioner within 90 days . Results Participation was significantly higher in the directly mailed group ( 38.0 % ) and in the opt-in group ( 30.9 % ) than in the control group ( 25.2 % ) ( participation difference ( PD ) : 12.8 % , 95 % CI : 10.6–15.0 % and PD : 5.7 % , 95 % CI : 3.5–7.9 % , respectively ) . Within 90 days , 107 women ( 90.7 % , 95 % CI : 83.9–95.3 % ) with a HPV-positive self- sample attended follow-up . Conclusions Offering the opportunity of HPV self-sampling as an alternative to regular cytology screening increased participation ; the direct mailing strategy was the most effective invitation strategy . A high compliance with follow-up was seen . Trial registration Current Controlled Trials NCT02680262 . Registered 10 February 2016 Background Ethnic minority women are at increased risk of cervical cancer . Self-sampling for high-risk human papillomavirus ( HPV ) is a promising approach to increase cervical screening among hard-to-reach population s. Objective To compare a community health worker (CHW)-led HPV self-sampling intervention with st and ard cervical cancer screening approaches . Design A 26-week single-blind r and omized pragmatic clinical trial . Participants From October 6 , 2011 to July 7 , 2014 , a total of 601 Black , Haitian , and Hispanic women aged 30–65 years in need of cervical cancer screening were recruited , 479 of whom completed study follow-up . Interventions Participants were r and omized into three groups : ( 1 ) outreach by CHWs and provision of culturally tailored cervical cancer screening information ( outreach ) , ( 2 ) individualized CHW-led education and navigation to local health care facilities for Pap smear ( navigation ) , or ( 3 ) individualized CHW-led education with a choice of HPV self-sampling or CHW-facilitated navigation to Pap smear ( self-swab option).Main Measures The proportion of women in each group whom self-reported completion of cervical cancer screening . Women lost to follow-up were considered as not having been screened . Key Results Of the 601 women enrolled , 355 ( 59 % ) were Hispanic , 210 ( 35 % ) were Haitian , and 36 ( 6 % ) were non-Haitian Black . In intent-to-treat analyses , 160 of 207 ( 77 % ) of women in the self-swab option group completed cervical cancer screening versus 57 of 182 ( 31 % ) in the outreach group ( aOR 95 % CI , p < 0.01 ) and 90 of 212 ( 43 % ) in the navigation group ( aOR CI , p = 0.02 ) . Conclusions As compared to more traditional approaches , CHW-facilitated HPV self-sampling led to increased cervical cancer screening among ethnic minority women in South Florida . Trial Registration Clinical Trials.gov Identifier : We conducted a r and omized , controlled trial to evaluate different strategies of offering an HPV-self sampling program , and compared this with two control groups . All total of 35,354 women who did not participate in the Flemish cancer screening program were included in the study : 9,118 received a HPV self- collection brush ( RIATOL qPCR HPV genotyping test ( qPCR [ E6/E7 ] ) ; 9,098 were offered the opportunity to order an HPV-selfsampling brush , 8,830 received the recall letter ; 8,849 received no intervention . Within 12 months after the mailing , 18.7 % of the women who had received the brush , participated by returning a self- sample sample , while 10.6 % women allocated to the opt- in group did so . 10.5 % women who received the st and ard recall letter , had a PAP smear taken within a period of 12 months ; while 8 % women did so without receiving an intervention at all . Participation in postmenopausal women was higher than in women younger than 50 in both self-sampling arms . Screening by means of the self- sample kit increased by age , contradictory when screening is performed by a PAP smear . Of those testing hrHPV positive ( 9.5 % ) , 88.9 % attended for follow up cytology . The mean DNA concentration , found in the self- sample r , decreased by age , causing a higher number of inconclusive results . Our results support the efficacy of a self-sampling strategy to increase participation in the Flemish screening program . Self-sampling seems particularly acceptable to postmenopausal non-responders . Future research should focus on the performance of different self-sampling devices in post-menopausal women as low DNA concentrations exponentially increased over age BACKGROUND Our aim was to determine if cervical cancer screening uptake would increase among under-screened women living in rural Ontario , Canada , if at-home self-collected sampling for human papillomavirus ( HPV ) testing was offered as a primary cervical cancer screening modality , compared to invited papanicolaou ( Pap ) testing or routine opportunistic screening . METHODS Women 30 - 70 years of age who were overdue for cervical cancer screening were r and omized to receive ( 1 ) an at-home self-collected HPV kit , ( 2 ) a reminder invitation for Pap testing , or ( 3 ) st and ard of care opportunistic screening . The first two arms were also asked demographic and screening history questions . Women r and omized to arm 1 were asked about acceptability . RESULTS In total , 818 eligible women were identified in a small rural community in Southwestern Ontario : 335 received a self-collected HPV testing kit , 331 received a reminder letter , and 152 received st and ard of care . In the HPV self- collection arm , 21 % ( 70/335 ) returned the sample and question naire and 11 % ( 37/335 ) opted to undergo Pap testing . In total , 32 % from the HPV self- collection arm , 15 % ( 51/331 ) from the Pap invitation arm , and 8.5 % ( 13/152 ) with st and ard of care were screened . Women receiving the self-collected HPV kit were 3.7 ( 95 % confidence interval 2.2 - 6.4 ) times more likely to undergo screening compared to the st and ard of care arm . In the HPV self-sampling arm , 80 % ( 56/70 ) said they would be very likely to choose self-collected sampling in the future . CONCLUSIONS Providing self-collected sampling for HPV testing was more effective than sending reminder letters to increase screening coverage in under-screened women RACOMIP is a population ‐based , r and omized trial of the effectiveness and cost‐effectiveness of different interventions aim ed at increasing participation in a well‐run cervical cancer screening program in western Sweden . In this article , we report results from one intervention , offering non‐attendees a high‐risk human papillomavirus ( HPV ) self‐test . Comparison was made with st and ard screening invitation routine or st and ard routine plus a telephone call . Women ( 8,800 ) , aged 30–62 , were r and omly selected among women without a registered Pap smear in the two latest screening rounds . These women were r and omized 1:5:5 to one of three arms : 800 were offered a high‐risk HPV self‐test , 4,000 were r and omized to a telephone call ( reported previously ) and 4,000 constituted a control group ( st and ard screening invitation routine ) . Results were based on intention to treat analysis and cost‐effectiveness was calculated as marginal cost per cancer case prevented . The endpoint was the frequency of testing . The total response rate in the self‐testing arm was 24.5 % , significantly higher than in the telephone arm ( 18 % , RR 1.36 , 95 % CI 1.19–1.57 ) and the control group ( 10.6 % , RR 2.33 , 95 % CI 2.00–2.71 ) . All nine women who tested positive for high‐risk HPV attended for a cervical smear and colposcopy . From the health‐care sector perspective , the intervention will most likely lead to no additional cost . Offering a self‐test for HPV as an alternative to Pap smears increases participation among long‐term non‐attendees . Offering various screening options can be a successful method for increasing participation in this group We evaluated the effect of offering brush-based vaginal self-sampling for high-risk human papillomavirus ( hrHPV ) testing to non-attendees of the cervical screening program on response rate , compliance to follow-up and cervical intraepithelial neoplasia grade 2 or 3 ( CIN2+/CIN3 + ) yield . In addition , concordance of hrHPV test results between physician-taken cervical scrapes and vaginal self- sample s was determined . A total of 26,409 nonattending women were r and omly assigned to receive a vaginal brush device for hrHPV testing by Hybrid Capture-2 method ( i.e. , self-sampling group , n = 26,145 ) or a reinvitation for regular cytology-based screening ( i.e. , recall control group , n = 264 ) . hrHPV-positive self-sampling responders were invited for a physician-taken scrape for cytology and blinded hrHPV testing . If cytology was abnormal , women were referred for colposcopy . Response rate in the self-sampling group was significantly increased compared to the recall control group ( 30.8 % versus 6.5 % ; p < 0.001 ) . The concordance rate between hrHPV detection in self- sample s and corresponding physician-taken cervical scrape sample s was 68.8 % . Amongst women with CIN3 + and CIN2 + , the concordance rates in hrHPV positivity between both sample s were 95.5 % and 93.8 % , respectively . Adherence at baseline to cytology triage of hrHPV-positive self-sampling women ( 89.1 % ) and colposcopy referral of those with abnormal cytology ( 95.8 % ) was high . The CIN2+/CIN3+/carcinoma yields were 1.5 % , 1.0 % and 0.1 % , respectively , in self-sampling responders . In conclusion , offering hrHPV testing on self- sample d vaginal material with a brush device to non-attendees significantly increases the attendance to the regular screening program , yields hrHPV test results that are in very good concordance with those of physician-taken scrapes in women with CIN2+/CIN3 + , and is effective in detecting CIN2+/CIN3 + Offering self-sampling devices improves participation of under-screened women . We evaluated participation in routine screening following the self-sampling intervention in two organized population -based screening programmes located in North-East Italy . Data on participation at 3-years-interval after a r and omized clinical trial assessing the response to two strategies offering self- sample rs ( sent at home or offered free at local pharmacy ) with a control action ( sending reminders for a cervical specimen taken at the clinic ) in 30–64 yr-old women non-respondent to the regular call-recall invitation were analyzed . Up to April 2016 , 2300 women out of the 2995 recruited in the trial in 2011 were re-invited to perform a screening test at clinic ; overall , 698 women adhered . Participation was similar in the three arms ( 29–32 % ) , and highest ( 47–68 % ) among those who participated in the previous round . Over the two rounds , 44.6 % , 32.3 % and 30.3 % women had at least one test in the self-sampling at home , self-sampling at pharmacy and test at the clinic arms , respectively . Our data indicate that the beneficial effect of offering self-sampling devices to nonparticipating women is maintained over time . Self- sample rs are useful to increase overall coverage ; their sporadic use does not seem to increase the proportion of women regularly repeating the test Background : Attendance in screening is an important determinant of cervical cancer . Previous experience on high-risk human papillomavirus ( hrHPV ) DNA testing on patient-obtained sample s suggests a good effect among nonattendees of screening . We assessed the effects of self-sampling on attendance in the Finnish screening program . Methods : Nonattendees after the primary invitation in one municipality ( Espoo ) were r and omized to receive either a self-sampling kit ( 2,397 women ) or an extra invitation ( 6,302 women ) . One fourth ( 1,315 women ) of reminder letter arm nonattendees also received a self-sampling kit as a third intervention . Main outcomes were increases in screening attendance and coverage . Results : The adjusted relative risk for participation by self-sampling as a second intervention in comparison to a reminder letter arm was 1.21 ( 95 % CI : 1.13–1.30 ) . Total attendance increased from 65 % to 76 % by self-sampling and from 65 % to 74 % with a reminder letter . Combining the interventions ( reminder letter and then self-sampling ) increased total attendance from 63 % to 78 % . One fifth of the participants in all three groups increased screening coverage ( previous Pap smear ≥5 years ago or never ) . Self-obtained sample s were more often HPV positive than provider-obtained ones ( participants after primary invitation and reminder letter ) , 12 % to 13 % versus 7 % . Conclusions : Self-sampling is a feasible option in enhancing the attendance at organized screening , particularly as an addition to a reminder letter . Impact : If self-sampling is used as a third intervention after two written invitations , the overall attendance in Finl and could most likely reach the desired 80 % to 85 % . Cancer Epidemiol Biomarkers Prev ; 20(9 ) ; 1960–9 . © 2011 AACR Background : Most women with cervical cancer have not participated in Pap-smear screening . Self-sampling of vaginal fluid in combination with high-risk HPV testing may be a method to increase the attendance rate . Methods : A total of 4060 women , 39–60 years old , who had not attended the organised Pap-smear screening for 6 years or more were r and omised into two equal groups . A study group was offered to self- sample vaginal fluid ( Qvintip ) at home and /or recommended to attend the Pap-smear screening . The collected fluid after self-sampling was examined for the presence of high-risk HPV ( Hybrid Capture 2 method ) . Controls were only recommended to attend the Pap-smear screening . The end point was a histological identification of CIN2–3 . Results : The participation rate was 39 % ( 771 out of 2000 ) in the self-sampling group and 9 % ( 188 out of 2060 ) in the conventional cytology ( P<0.001 ) . The number of histological CIN2–3 alterations detected was 0.4 % ( 8 out of 2000 ) among women offered self-sampling of vaginal fluid and 0.07 % ( 3 out of 4060 ) in women offered Pap-smears . The odds ratio ( OR ) for offering self-sampling and HPV testing instead of Pap-smear screening for detection of CIN2–3 was OR=5.42 ( 95 % CI : 1.30–31.8 ) . Conclusion : Offering self-sampling of vaginal fluid followed by a high-risk HPV test was considerably more effective for detection of histological CIN2–3 lesions in comparison with offering Pap-test in a midwife reception in women not regularly attending organised screening Background : We performed a multicentre r and omised controlled trial to evaluate the effect on participation in organised screening programmes of a self-sampling device mailed home or picked up at a pharmacy compared with the st and ard recall letter . Methods : Women aged 30–64 non-responding to screening invitation were eligible . Response rate to first invitation ranged from 30 % to 60 % between centres . The control was the st and ard reminder letter to undergo the test used by the programme ( Pap test in three centres and HPV DNA test in three other centres ) . Home mailing of the self- sample r was preceded by a letter with a leaflet about HPV . The analysis was intention-to-treat . Results : In all , 14 041 women were r and omised and recruited : 5012 in the control arm , 4516 to receive the self- sample r at home , and 4513 to pick up the self- sample r at a pharmacy . Participation was 11.9 % in the control , 21.6 % ( relative participation : 1.75 ; 95 % CI 1.60–1.93 ) in home , and 12.0 % ( relative participation : 0.96 ; 95 % CI 0.86–1.07 ) in the pharmacy arms , respectively . The heterogeneity between centres was high ( excess heterogeneity of that expected due to chance , i.e. , I2 , 94.9 % and 94.1 % for home and pharmacy arm , respectively ) . The estimated impact on the overall coverage was + 4.3 % for home mail self-sampling compared with + 2.2 % for st and ard reminder . Conclusions : Home mailing of self- sample r proved to be an effective way to increase participation in screening programmes , even in those with HPV as primary testing . Picking up at pharmacies showed effects varying from centre to centre Objective To determine whether offering self sampling of cervicovaginal material for high risk human papillomavirus ( HPV ) testing is an effective screening method for women who do not attend regular cervical screening programmes . Design Cohort study ( the PROHTECT trial ) . Setting s Noord-Holl and and Flevol and regions of the Netherl and s , December 2006 to December 2007 , including 13 laboratories , gynaecologists , and more than 800 general practitioners . Participants 28 073 women who had not responded to two invitations to the regular cervical screening programme : 27 792 women were assigned to the self sampling group and invited to su bmi t a self collected cervicovaginal sample for HPV testing ; 281 were assigned to the recall control group and received a second re-invitation for conventional cytology . Intervention Women with a positive result on the high risk HPV test on their self sample material were referred to their general practitioner . Women with abnormal results on cytology were referred for colposcopy . Women with normal results on cytology were re-evaluated after one year by cytology and high risk HPV testing and referred for colposcopy if either result was positive . Main outcome measures Attendance rate in both groups and yield of cervical intraepithelial neoplasia grade II/III or worse ( ≥CIN II/≥CIN III ) in self sampling responders . Results The compliance rate in the self sampling group was significantly higher than in the control group ( crude 26.6 % v 16.4 % , P<0.001 ; adjusted 27.5 % v 16.6 % , P<0.001 ) . The number of detected ≥CIN II and ≥CIN III lesions in self sampling responders was 99 ( 1.3 % ) and 76 ( 1.0 % ) , respectively . Self sampling responders who had not participated in the previous round of screening ( 43 % ) had increased relative risks of ≥CIN II ( 2.04 , 95 % confidence interval 1.27 to 3.28 ) and ≥CIN III ( 2.28 , 1.31 to 3.96 ) compared with self sampling women who had been screened in the previous round ( 57 % ) . Conclusions Offering self sampling by sending a device for collecting cervicovaginal specimens for high risk HPV testing to women who did not attend regular screening is a feasible and effective method of increasing coverage in a screening programme . The response rate and the yield of high grade lesions support implementation of this method for such women . Trial registration IS RCT N45527158 Background : Cervical cancer screening coverage remains insufficient in most countries . Our objective was to assess whether in-home vaginal self-sampling with a dry swab for high-risk human papillomavirus ( HR-HPV ) testing is effective and cost-effective in increasing participation in cervical cancer screening . Methods : In March 2012 , 6000 unscreened women aged 30–65 years , living in a French region covered by a screening programme , who had not responded to an initial invitation to have a Pap smear were equally r and omised to three groups : ‘ no intervention ’ ; ‘ recall ’ , women received a letter to have a Pap smear ; and ‘ self-sampling ’ , women received a self-sampling kit to return to a central ised virology laboratory for PCR-based HPV testing . Results : Participation was higher in the ‘ self-sampling ’ than in the ‘ no intervention ’ group ( 22.5 % vs 9.9 % , P<0.0001 ; OR 2.64 ) and ‘ recall ’ group ( 11.7 % , P<0.0001 ; OR 2.20 ) . In the ‘ self-sampling ’ group , 320 used the self-sampling kit ; for 44 of these women with positive HR-HPV test results , 40 had the recommended triage Pap smear . The ICER per extra screened woman was 77.8[euro ] and 63.2[euro ] for the ‘ recall ’ and ‘ self-sampling ’ groups , respectively , relative to the ‘ no intervention ’ group . Conclusions : Offering an in-home , return-mail kit for vaginal self-sampling with a dry swab is more effective and cost-effective than a recall letter in increasing participation in cervical cancer screening Background Cervical cancer incidence and mortality rates in Sub-Saharan Africa ( SSA ) remain high due to several factors including low levels of uptake of cervical cancer screening . Self- collection of cervicovaginal sample s for HPV DNA testing may be an effective modality that can increase uptake of cervical cancer screening in SSA and hard to reach population s in developed countries . We investigated whether self- collection of cervicovaginal sample s for HPV DNA tests would be associated with increased uptake of screening compared with clinic based collection of sample s. Furthermore , we compared the quality of sample s collected by both approaches for use in HPV genotyping . Methods We conducted a community based r and omized trial in a semi-urban district of Abuja , Nigeria with 400 women , aged 30 to 65 years r and omized to either hospital- collection or self- collection of cervicovaginal sample s. We compared cervical cancer screening uptake among the 2 groups and evaluated the concentration of human DNA in the sample s by measuring RNase P gene levels using qPCR . High-risk HPV DNA detection and typing was done using the GP5+/6 + Luminex system . Results Most participants in the self- collection arm ( 93 % , 185/200 ) su bmi tted their sample s while only 56 % ( 113/200 ) of those invited to the hospital for sample collection attended and were screened during the study period ( p value < 0.001 ) . Human genomic DNA was detected in all but five ( 1.7 % ) participants , all of whom were in the self- collection arm . The prevalence of high-risk HPV in the study population was 10 % with types 35 , 52 and 18 being the commonest . Conclusions Our study shows that self-sampling significantly increased uptake of HPV DNA based test for cervical cancer screening in this population and the sample s collected were adequate for HPV detection and genotyping . Cervical cancer screening programs that incorporate self-sampling and HPV DNA tests are feasible and may significantly improve uptake of cervical cancer screening in SSA Background : The aim of this study is to evaluate whether self-sampling can increase screening attendance of women who do not attend regular screening in Switzerl and . Methods : Participants were proactively recruited in Geneva between September 2011 and November 2015 . Women ( 25–69 years ) who had not undergone CC screening in the last 3 years were considered eligible . Through a 1 : 1 ratio r and omisation , enrolled participants were invited to either undergo liquid-based cytology , which was performed by a health-care provider ( control group , CG ) or to take a self- sample for HPV-testing , which was mailed to their home ( intervention group , IG ) . Results : A total of 331 and 336 women were r and omised in the CG and in the IG , respectively . Overall , 7.3 % ( 95 % CI : 4.9–10.6 ) women in the CG and 5.7 % ( 95 % CI : 3.6–8.7 ) women in the IG did not undergo the initial screening ( P=0.400 ) . There were 1.95 % ( 95 % CI : 0.8–4.3 ) women in the CG and 5.05 % ( 95 % CI : 3.1–8.1 ) women in the IG with a positive screen who did not attend triage and colposcopy ( P=0.036 ) . Conclusions : The participation in CC screening in women offered self-sampling was not higher than among those offered specimen collection by a clinician . Compliance with further follow-up for women with a positive HPV test on the self- sample requires further attention We conducted a r and omized controlled trial to determine whether HPV self-sampling increases participation in cervical screening by never- and under-screened ( not screened in past 5 years ) women when compared with a reminder letter for a Pap test . Never- or under-screened Victorian women aged 30 - 69 years , not pregnant and with no prior hysterectomy were eligible . Within each stratum ( never-screened and under-screened ) , we r and omly allocated 7,140 women to self-sampling and 1,020 to Pap test reminders . The self-sampling kit comprised a nylon tipped flocked swab enclosed in a dry plastic tube . The primary outcome was participation , as indicated by returning a swab or undergoing a Pap test ; the secondary outcome , for women in the self-sampling arm with a positive HPV test , was undergoing appropriate clinical investigation . The Roche Cobas ® 4800 test was used to measure presence of HPV DNA . Participation was higher for the self-sampling arm : 20.3 versus 6.0 % for never-screened women ( absolute difference 14.4 % , 95 % CI : 12.6 - 16.1 % , p < 0.001 ) and 11.5 versus 6.4 % for under-screened women ( difference 5.1 % , 95 % CI : 3.4 - 6.8 % , p < 0.001 ) . Of the 1,649 women who returned a swab , 45 ( 2.7 % ) were positive for HPV16/18 and 95 ( 5.8 % ) were positive for other high-risk HPV types . Within 6 months , 28 ( 62.2 % ) women positive for HPV16/18 had colposcopy as recommended and nine ( 20 % ) had cytology only . Of women positive for other high-risk HPV types , 78 ( 82.1 % ) had a Pap test as recommended . HPV self-sampling improves participation in cervical screening for never- and under-screened women and most women with HPV detected have appropriate clinical investigation Today in France , low attendance to cervical screening by Papanicolaou cytology ( Pap-smear ) is a major contributor to the 3,000 new cervical cancer cases and 1,000 deaths that occur from this disease every year . Nonattenders are mostly from lower socioeconomic groups and testing of self-obtained sample s for high-risk Human Papilloma virus ( HPV ) types has been proposed as a method to increase screening participation in these groups . In 2011 , we conducted a r and omized study of women aged 35 - 69 from very low-income population s around Marseille who had not responded to an initial invitation for a free Pap-smear . After r and omization , one group received a second invitation for a free Pap-smear and the other group was offered a free self-sampling kit for HPV testing . Participation rates were significantly different between the two groups with only 2.0 % of women attending for a Pap-smear while 18.3 % of women returned a self- sample for HPV testing ( p ≤ 0.001 ) . The detection rate of high- grade lesions ( ≥CIN2 ) was 0.2‰ in the Pap-smear group and 1.25‰ in the self-sampling group ( p = 0.01 ) . Offering self-sampling increased participation rates while the use of HPV testing increased the detection of cervical lesions ( ≥CIN2 ) in comparison to the group of women receiving a second invitation for a Pap-smear . However , low compliance to follow-up in the self-sampling group reduces the effectiveness of this screening approach in nonattenders women and must be carefully managed Objective Women living with HIV experience higher risk of cervical cancer , but screening rates in the United States are lower than recommended . The purpose of this study was to examine whether an intervention using self-sampling of cervicovaginal cells for human papillomavirus ( HPV ) with results counseling would increase cervical cytology ( “ Pap ” ) testing among women with HIV . Material s and Methods This was a r and omized controlled trial to test the effectiveness of an intervention of self-sampling for HPV and results counseling . Participants were 94 women older than 18 years , with HIV infection , attending an HIV clinic for a primary care visit , whose last cervical cancer screening was 18 months or more before baseline . Women were assigned to the intervention or information-only group . The primary outcome was completion of cervical cytology testing within 6 months of baseline . The secondary outcome was the women 's perceived threat of developing cervical cancer . Results A total of 94 women were enrolled and analyzed in the study . The cytology completion rate overall was 35 % by 6 months from baseline . There were no differences in comparing HPV-positive with HPV-negative women nor comparing them with the information-only group . In the intervention group , a positive HPV test increased perceived threat of cervical cancer . Conclusions The intervention did not improve cytology test attendance , although education about HPV and cervical cancer risk as part of study procedures was associated with testing for 35 % of this group of women whose previous cytology occurred an average of 3.6 years before the baseline appointment . Self-sampling for HPV testing was feasible BACKGROUND Many cervical cancers occur among women who have not attended cervical screening . Strategies to reach non-attending women may improve the effectiveness of cervical screening programmes . OBJECTIVE To compare the responses among long-term non-attending women to either ( i ) HPV-testing of a self-collected vaginal sample , or ( ii ) cytological screening with a flexible no-fee appointment for sampling at an outpatient clinic . STUDY DESIGN Among the 242,000 women aged 32 - 65 years in Southern Sweden , we identified 28,635 women who had not had any cervical smears taken for > 9 years . We r and omized 1000 women to invitation to HPV self-sampling , and 500 women to flexible outpatient clinic appointments . Responding women received a question naire about their reasons for previous non-attendance . RESULTS The response rate to HPV self-sampling was three times higher than the flexible outpatient clinic invitations ( 147/1000 women ( 14.7 % ) compared to 21/500 ( 4.2 % ) p<0.0001 ) . High-risk (hr)-HPV was found in 10/147 self- sample d women ( 6.9 % ) . 7/10 hr-HPV-positive women attended colposcopy , but no HSIL was found . Among the clinic- sample d women , 2/21 had hr-HPV and 1/21 had HSIL . Reasons for not attending were " uncomfortable with vaginal examination " , " feel healthy " , " lack of time " and " experience of unfriendly health workers " . CONCLUSIONS Although the response rate was low for both interventions , the invitation to vaginal HPV self-sampling was more effective for increasing the coverage of the screening programme . The fact that " uncomfortable with vaginal examination " was the most common reason for non-attending suggests that self-sampling could be further explored as a strategy to increase the coverage of cervical screening programmes Background Non-attenders for cervical screening are at increased risk of cervical cancer . Studies offering self-sampling for high-risk Human Papillomavirus ( HrHPV ) testing have shown greater uptake than sending another invitation for cytology . Objectives To explore whether uptake would increase in a less diverse , more stable population than the previous English study , which demonstrated a lower response rate than other studies . The primary objective was whether non-attenders were more likely to respond to a postal invitation , including kit , to collect a self- sample compared with a further invitation for cytology screening . The secondary objective was whether women with an abnormal result would attend for follow-up . Methods 6000 non-attenders for screening in this pragmatic , r and omized ( 1:1 ) controlled trial in Newcastle-upon-Tyne were sent an HPV self- sample kit ( intervention ) or a further invitation for cytology screening ( comparator ) . Results 411(13 % ) responded to the intervention , returning a self- sample ( 247(8 % ) ) or attending for cytology ( 164(5 % ) ) , compared with 183(6 % ) attending for cytology , relative risk 2.25 ( 95 % CI 1.90–2.65 ) ( comparator arm ) . Of those testing hrHPV positive ( 32(13 % ) ) , 19(59 % ) subsequently attended cytology screening . Of those in the intervention group who attended for cytology screening without returning an hrHPV self- sample ( n = 164 ) , 5 % ( n = 8) were referred for colposcopy - all attended . In the comparator group eight of the nine referred for colposcopy attended . Conclusion Persistent non-responders to invitations for cervical screening are significantly more likely to respond to a postal invitation to return a self-collected sample for HPV testing than a further invitation for cytology screening . However , just over half followed up on this positive HPV result BACKGROUND Vaginal self-sampling for human papillomavirus ( HPV ) DNA testing could increase rates of screening participation . In clinic-based setting s , vaginal HPV testing is at least as sensitive as cytology for detecting cervical intraepithelial neoplasia ( CIN ) grade 2 or worse ; however , effectiveness in home setting s is unknown . We aim ed to establish the relative sensitivity and positive predictive value for HPV screening of vaginal sample s self-collected at home as compared with clinic-based cervical cytology . METHODS We did a community-based , r and omised equivalence trial in Mexican women of low socioeconomic status aged 25 - 65 years . Participants came from 540 medically underserved , predominantly rural communities in Morelos , Guerrero , and the state of Mexico . Our primary endpoint was CIN 2 or worse , detected by colposcopy . We used a computer-generated r and omisation sequence to r and omly allocate patients to HPV screening or cervical cytology . Eight community nurses who were masked to patient allocation received daily lists of the women 's names and addresses , and did the assigned home visits . We referred women with positive results in either test to colposcopy . We did per- protocol and intention-to-screen analyses . This trial was registered with the Instituto Nacional de Salud Pública , Mexico , INSP number 590 . FINDINGS 12,330 women were r and omly allocated to HPV screening and 12,731 to cervical cytology ; 9202 women in the HPV screening group adhered to the protocol , as did 11,054 in the cervical cytology group . HPV prevalence was 9·8 % ( 95 % CI 9·1 - 10·4 ) and abnormal cytology rate was 0·38 % ( 0·23 - 0·45 ) . HPV testing identified 117·4 women with CIN 2 or worse per 10,000 ( 95·2 - 139·5 ) compared with 34·4 women with CIN 2 or worse per 10,000 ( 23·4 - 45·3 ) identified by cytology ; the relative sensitivity of HPV testing was 3·4 times greater ( 2·4 - 4·9 ) . Similarly , HPV testing detected 4·2 times ( 1·9 - 9·2 ) more invasive cancers than did cytology ( 30·4 per 10,000 [ 19·1 - 41·7 ] vs 7·2 per 10,000 [ 2·2 - 12·3 ] ) . The positive predictive value of HPV testing for CIN 2 or worse was 12·2 % ( 9·9 - 14·5 ) compared with 90·5 % ( 61·7 - 100 ) for cytology . INTERPRETATION Despite the much lower positive predictive value for HPV testing of self-collected vaginal specimens compared with cytology , such testing might be preferred for detecting CIN 2 or worse in low-re source setting s where restricted infrastructure reduces the effectiveness of cytology screening programmes . Because women at these sites will be screened only a few times in their lives , the high sensitivity of a HPV screen is of paramount importance . FUNDING Instituto Nacional de Salud Pública , the Health Ministry of Mexico , QiAGEN Background Participation in cervical cancer screening varies by socioeconomic status . The aims were to assess if offering human papilloma virus ( HPV ) self-sampling kits has an effect on screening participation among various socioeconomic groups and to determine if two invitation strategies for offering self-sampling influence the participation rate equally . Methods The study was based on registry data that were applied to data from a r and omized controlled trial ( n=9,791 ) measuring how offering HPV self-sampling affected screening participation . The women received either 1 ) a self-sampling kit mailed directly to their homes ( directly mailed group ) ; 2 ) an invitation to order the kit ( opt-in group ) ; or 3 ) a st and ard second reminder to attend regular cytology screening ( control group ) . The participation data were linked to registries containing socioeconomic information . Results Women in the directly mailed group participated significantly more than women in the control group , regardless of their socioeconomic status , but the largest effects were observed in Western immigrants ( participation difference [PD]=18.1 % , 95 % CI=10.2%–26.0 % ) and social welfare recipients ( PD=15.2 % , 95 % CI=9.7%–20.6 % ) . Compared with the control group , opt-in self-sampling only had an insignificant effect on participation among women who were immigrants , retired , or less educated . Western immigrants had a significantly higher increase in participation than native Danish women when kits were mailed directly compared with the opt-in strategy ( PD=18.1 % , 95 % CI=10.2%–26.2 % and PD=5.5 % , 95 % CI=2.9%–8.1 % , respectively , P=0.01 ) . Conclusion All socioeconomic groups benefited from the directly mailed strategy in terms of higher screening participation , but Western immigrants and lower socioeconomic groups seemed to benefit the most . Immigrants and some lower socioeconomic groups only had insignificant benefits of opt-in self-sampling . The directly mailed strategy might be preferable to opt-in self-sampling because it ensures that ethnic minority groups obtain benefits of introducing HPV self-sampling in an organized cervical cancer screening program . Trial registration Current Controlled Trials NCT02680262 . Registered February 10 , 2016 Abstract Background To overcome obstacles within the Slovenian organised cervical cancer screening programme , a r and omised pilot study of human papillomavirus ( HPV ) self-sampling among non-attenders was performed , aim ing to assess three different screening approaches . Participants and methods Non-attenders aged 30–64 years from two Slovenian regions were r and omised to two HPV self-sampling groups – the opt-in ( I1 , n = 14.400 ) and the opt-out ( I2 , n = 9.556 ) , with a control group ( P , n = 2.600 ) . Self-collected sample s were analysed using the Hybrid Capture 2 assay . HPV-positive women were invited to a colposcopy . The overall and type-specific intention-to-screen response rates and histological outcomes with a positive predictive value ( PPV ) according to the women ’s age , the screening approach , the level of protection result ing from previous screening history , and the region of residence were assessed . Results Of the 26.556 women enrolled , 8.972 ( 33.8 % ) responded with self- sample for HPV testing and /or traditional cytology within one year of enrolment . Response rates were 37.7 % , 34.0 % and 18.4 % ( p < 0.050 ) for opt-out , opt-in and control groups . Cervical intraepithelial neoplasia (CIN)2 + was diagnosed in 3.9/1.000 , 3.4/1.000 , and 3.1/1.000 women ( p > 0.050 ) , respectively . PPV of the HPV self-sampling was 12.0 % and 9.6 % for CIN2 + and CIN3 + . The highest PPV was obtained in non-attenders in screening programme for more than 10-years and concordant results of HPV testing with 40.8 % for CIN2 + and 38.8 % for CIN3 + . Conclusions The results of our study show that a high response to HPV self-sampling can be achieved also in an opt-in approach , if women are encouraged to choose between self-sampling at home and screening with gynaecologist . In addition , clinical ly important risk difference for a high- grade cervical lesion exists in the case of a positive result of HPV testing on self-collected sample s , depending on the length of the interval since last screening . Stratified management of these women should be strongly considered . Women who were not screened with cytology for at least 10 years should be referred to immediate colposcopy for histology verification instead to delayed re-testing Background Different tools exist for assessing risk of bias of intervention studies for systematic review s. We present a tool for assessing risk of bias across both r and omized and non-r and omized study design s. The tool was developed by the Evidence Project , which conducts systematic review s and meta-analyses of behavioral interventions for HIV in low- and middle-income countries . Methods We present the eight items of the tool and describe considerations for each and for the tool as a whole . We then evaluate reliability of the tool by presenting inter-rater reliability for 125 selected studies from seven published review s , calculating a kappa for each individual item and a weighted kappa for the total count of items . Results The tool includes eight items , each of which is rated as being present ( yes ) or not present ( no ) and , for some items , not applicable or not reported . The items include ( 1 ) cohort , ( 2 ) control or comparison group , ( 3 ) pre-post intervention data , ( 4 ) r and om assignment of participants to the intervention , ( 5 ) r and om selection of participants for assessment , ( 6 ) follow-up rate of 80 % or more , ( 7 ) comparison groups equivalent on sociodemographics , and ( 8) comparison groups equivalent at baseline on outcome measures . Together , items (1)–(3 ) summarize the study design , while the remaining items consider other common elements of study rigor . Inter-rater reliability was moderate to substantial for all items , ranging from 0.41 to 0.80 ( median κ = 0.66 ) . Agreement between raters on the total count of items endorsed was also substantial ( κw = 0.66 ) . Conclusions Strengths of the tool include its applicability to a range of study design s , from r and omized trials to various types of observational and quasi-experimental studies . It is relatively easy to use and interpret and can be applied to a range of review topics without adaptation , facilitating comparability across review s. Limitations include the lack of potentially relevant items measured in other tools and potential threats to validity of some items . To date , the tool has been applied in over 30 review s. We believe it is a practical option for assessing risk of bias in systematic review s of interventions that include a range of study design BACKGROUND Control of cervical cancer in developing countries has been hampered by a failure to achieve high screening uptake . HPV DNA self- collection could increase screening coverage , but implementation of this technology is difficult in countries of middle and low income . We investigated whether offering HPV DNA self- collection during routine home visits by community health workers could increase cervical screening . METHODS We did a population -based cluster-r and omised trial in the province of Jujuy , Argentina , between July 1 , 2012 , and Dec 31 , 2012 . Community health workers were eligible for the study if they scored highly on a performance score , and women aged 30 years or older were eligible for enrolment by the community health worker . 200 community health workers were r and omly allocated in a 1:1 ratio to either the intervention group ( offered women the chance to self-collect a sample for cervical screening during a home visit ) or the control group ( advised women to attend a health clinic for cervical screening ) . The primary outcome was screening uptake , measured as the proportion of women having any HPV screening test within 6 months of the community health worker visit . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT02095561 . FINDINGS 100 community health workers were r and omly allocated to the intervention group and 100 were assigned to the control group ; nine did not take part . 191 participating community health workers ( 94 in the intervention group and 97 in the control group ) initially contacted 7650 women ; of 3632 women contacted by community health workers in the intervention group , 3049 agreed to participate ; of 4018 women contacted by community health workers in the control group , 2964 agreed to participate . 2618 ( 86 % ) of 3049 women in the intervention group had any HPV test within 6 months of the community health worker visit , compared with 599 ( 20 % ) of 2964 in the control group ( risk ratio 4·02 , 95 % CI 3·44 - 4·71 ) . INTERPRETATION Offering self- collection of sample s for HPV testing by community health workers during home visits result ed in a four-fold increase in screening uptake , showing that this strategy is effective to improve cervical screening coverage . This intervention reduces women 's barriers to screening and results in a substantial and rapid increase in coverage . Our findings suggest that HPV testing could be extended throughout Argentina and in other countries to increase cervical screening coverage . FUNDING Instituto Nacional del Cáncer ( Argentina ) |
13,596 | 31,426,850 | This process yielded five main recommendations : A strong recommendation against spinal stabilisation of patients with isolated penetrating trauma ; a weak recommendation against the prehospital use of a rigid cervical collar and a hard backboard for ABCDE-stable patients ; and a weak recommendation for the use of a vacuum mattress for patient transportation . | Traumatic spinal cord injury is a relatively rare injury in Denmark but may result in serious neurological consequences .
For decades , prehospital spinal stabilisation with a rigid cervical collar and a hard backboard has been considered to be the most appropriate procedure to prevent secondary spinal cord injuries during patient transportation .
However , the procedure has been question ed in recent years , due to the lack of high- quality studies supporting its efficacy .
A national interdisciplinary task force was therefore established to provide up date d clinical guidelines on prehospital procedures for spinal stabilisation of adult trauma patients in Denmark . | BACKGROUND Extrication and spinal immobilization in the trauma patient with unknown injuries is a common practice of emergency medical services . High-speed crashes occurring in open-wheel racing seldom result in extrication or spinal immobilization . OBJECTIVES To evaluate the safety of self-extrication in IndyCar ® ( Indianapolis , IN ) by comparing drivers self extricated with full spinal immobilization and subsequent radiation exposure . METHODS A retrospective review of prospect ively collected de-identified IndyCar ® crash and drivers ' medical records was performed at treating Level I trauma centers . One hundred thirty-five crash incidents involving drivers evaluated by a medical team were included . Any driver with severe multiple trauma was excluded due to distracting injuries . Drivers underwent st and ard protocol for postcrash injury . Diagnostic and treatment outcomes including spinal and neurologic injury , need for surgery , and radiation exposure were collected for review . RESULTS Self-extrication occurred in 121 ( 90 % ) crashes , and overall cumulative radiation exposure ranged from 100 to 250 mSv , or 0.82 - 2.06 mSv per driver . Extrication with full spinal immobilization occurred in 14 ( 10 % ) drivers , with overall cumulative radiation exposure ranging from 140 to 350 mSv , or 10 - 25 mSv per driver . A total of 29 injuries were identified , nine of which ( 31 % ) were spinal . In these , six were emergency medical services extricated and three self extricated . None were unstable spinal fractures result ing in surgical care , surgical disease , or neurologic deficit . CONCLUSION In our IndyCar ® racing experience , a protocol -led self-extrication system result ed in neither a mismanagement of an unstable spinal fracture nor neurological deficit , and reduced radiation exposure BACKGROUND Intoxication often prevents clinical clearance of the cervical spine ( Csp ) after trauma leading to prolonged immobilization even with a normal computed tomography ( CT ) scan . We evaluated the accuracy of CT at detecting clinical ly significant Csp injury , and surveyed participants on related opinions and practice . METHODS A prospect i ve multicenter study ( 2013–2015 ) at 17 centers . All adult blunt trauma patients underwent structured clinical examination and imaging including a Csp CT , with follow-up thru discharge . alcohol- and drug-intoxicated patients ( TOX+ ) were identified by serum and /or urine testing . Primary outcomes included the incidence and type of Csp injuries , the accuracy of CT scan , and the impact of TOX+ on the time to Csp clearance . A 36-item survey querying local protocol s , practice s , and opinions in the TOX+ population was administered . RESULTS Ten thous and one hundred ninety-one patients were prospect ively enrolled and underwent CT Csp during the initial trauma evaluation . The majority were men ( 67 % ) , had vehicular trauma or falls ( 83 % ) , with mean age of 48 years , and mean Injury Severity Score ( ISS ) of 11 . The overall incidence of Csp injury was 10.6 % . TOX+ comprised 30 % of the cohort ( 19 % EtOH only , 6 % drug only , and 5 % both ) . TOX+ were significantly younger ( 41 years vs. 51 years ; p < 0.01 ) but with similar mean Injury Severity Score ( 11 ) and Glasgow Coma Scale score ( 13 ) . The TOX+ cohort had a lower incidence of Csp injury versus nonintoxicated ( 8.4 % vs. 11.5 % ; p < 0.01 ) . In the TOX+ group , CT had a sensitivity of 94 % , specificity of 99.5 % , and negative predictive value ( NPV ) of 99.5 % for all Csp injuries . For clinical ly significant injuries , the NPV was 99.9 % , and there were no unstable Csp injuries missed by CT ( NPV , 100 % ) . When CT Csp was negative , TOX+ led to longer immobilization versus sober patients ( mean , 8 hours vs. 2 hours ; p < 0.01 ) , and prolonged immobilization ( > 12 hrs ) in 25 % . The survey showed marked variations in protocol s , definitions , and Csp clearance practice s among participating centers , although 100 % indicated willingness to change practice based on these data . CONCLUSION For intoxicated patients undergoing Csp imaging , CT scan was highly accurate and reliable for identifying clinical ly significant spine injuries , and had a 100 % NPV for identifying unstable injuries . CT-based clearance in TOX+ patients appears safe and may avoid unnecessary prolonged immobilization . There was wide disparity in practice s , definitions , and opinions among the participating centers . LEVEL OF EVIDENCE Diagnostic tests or criteria , level II OBJECTIVES To compare the incidences and severities of pain experienced by healthy volunteers undergoing spinal immobilization in the neutral position with and without occipital padding . To compare the incidence of pain when immobilized in the neutral position with the incidence in a nonneutral position . METHODS Thirty-nine healthy volunteers over the age of 18 years who had no acute pain or illness , were not pregnant , and had no history of back problems or surgery voluntarily participated in a prospect i ve , r and omized , crossover study conducted in a clinical laboratory setting . Appropriately sized rigid cervical collars were applied to the subjects , who were then immobilized on wooden backboards with their cervical spines maintained in the neutral position using towels ( padded ) or plywood ( unpadded ) under their occiputs . The subjects were secured to the board with straps , soft head blocks , and tape for 15 minutes to simulate a typical ambulance transport time . The straps , head blocks , and tape were removed , and the subjects remained on the board for an additional 45 minutes to simulate a typical emergency department experience . The subjects were then asked to identify the location(s ) of any pain on anterior and posterior body outlines and to indicate the corresponding severity of pain on a 10-cm visual analog scale . The subjects were also asked questions about movement , respiratory symptoms , and strap discomfort in an attempt to distract them from the true focus of the study ( i.e. , pain ) . A similar survey was given to each participant to complete 24 hours later . The same subjects were immobilized with the alternate occipital material a minimum of two weeks later utilizing the same procedure . They again completed both surveys . RESULTS Pain was reported by 76.9 % of the subjects following removal from the backboard for the unpadded trial and 69.2 % of the subjects following the padded trial ( p < 0.45 ) . Twenty-three percent ( 23.1 % ) of the subjects reported neck pain after the unpadded trial , while 38.5 % reported neck pain after the padded trial ( p < 0.07 ) . Occipital pain was reported by 35.9 % in the unpadded trial and 25.6 % in the padded trial ( p < 0.29 ) . Twenty-four hours later , pain was reported by 17.9 % of the subjects following the unpadded trial and 23.1 % of the subjects following the padded trial ( p < 0.63 ) . Eight percent ( 7.7 % ) reported neck pain 24 hours after the and unpadded trial and 12.8 % after the padded trial ( p < 0.5 ) . Occipital pain was reported by 7.7 % of the subjects 24 hours after the unpadded trial and 2.6 % after the padded trial ( p < 0.63 ) . This study had a power of 0.90 to detect a difference of 30 % between the trials . The authors found a significantly lower incidence of pain ( p < 0.01 ) and occipital pain ( p < 0.01 ) in their unpadded trial compared with that reported by Chan et al. , who used neither padding nor neutral positioning to immobilize subjects . CONCLUSIONS Pain is frequently reported by healthy volunteers following spinal immobilization . Occipital padding does not appear to significantly decrease the incidence or severity of pain . Alignment of the cervical spine in the neutral position may reduce the incidence of pain , but further studies should be conducted to substantiate this observation INTRODUCTION Traditional EMS teaching identifies mechanism of injury as an important predictor of spinal injury . Clinical criteria to select patients for immobilization are being studied in Michigan and have been implemented in Maine . Maine requires automatic immobilization of patients with " a positive mechanism " clearly capable of producing spinal injury . OBJECTIVE To determine whether mechanism of injury affects the ability of clinical criteria to identify patients with spinal injury . METHODS In this multicenter prospect i ve cohort study , EMS personnel completed a check-off data sheet for prehospital spine-immobilized patients . Data included mechanism of injury and yes/no determinations of the clinical criteria : altered mental status , neurologic deficit , evidence of intoxication , spinal pain or tenderness , and suspected extremity fracture . Hospital outcome data included confirmation of spinal injury and treatment required . Mechanisms of injury were tabulated and rates of spinal injury for each mechanism were calculated . The patients were divided into three different high-risk and low-risk groups . RESULTS Data were collected for 6,500 patients . There were 209 ( 3.2 % ) patients with spinal injuries identified . There were 1,058 patients with 100 ( 9.4 % ) injuries in the first high-risk mechanism group , and 5,423 patients with 109 ( 2 % ) injuries in the first low-risk group . Criteria identified 97 of 100 ( 97 % ) injuries in the high-risk group and 102 of 109 ( 94 % ) in the low-risk group . Two additional data divisions yielded identical results . CONCLUSION Mechanism of injury does not affect the ability of clinical criteria to predict spinal injury in this population BACKGROUND A distracting injury m and ates cervical spine ( c-spine ) imaging in the evaluable blunt trauma patient who demonstrates no pain or tenderness over the c-spine . The purpose of this study was to examine which distracting injuries can negatively affect the sensitivity of the st and ard clinical examination of the c-spine . METHODS This is a prospect i ve observational study conducted at a Level I Trauma Center from January 1 , 2008 , to December 31 , 2009 . After institutional review board approval , all evaluable ( Glasgow Coma Scale score ≥13 ) blunt trauma patients older than 16 years sustaining a c-spine injury were enrolled . A distracting injury was defined as any immediately evident bony or soft tissue injury or a complaint of non-c-spine pain whether or not an actual injury was subsequently diagnosed . Information regarding the initial clinical examination and the presence of a distracting injury was collected from the senior resident or attending trauma surgeon involved in the initial management . RESULTS During the study period , 101 evaluable patients sustained a c-spine injury . Distracting injuries were present in 88 patients ( 87.1 % ) . The most common was rib fracture ( 21.6 % ) , followed by lower extremity fracture ( 20.5 % ) and upper extremity fracture ( 12.5 % ) . Only four ( 4.0 % ) patients had no pain or tenderness on the initial examination of the c-spine . All four patients had bruising and tenderness to the upper anterior chest . None of these four patients developed neurologic sequelae or required a surgical stabilization or immobilization . CONCLUSION C-spine imaging may not be required in the evaluable blunt trauma patient despite distracting injuries in any body regions that do not involve the upper chest . Further definition of distracting injuries is m and ated to avoid unnecessary utilization of re sources and to reduce the imaging burden associated with the evaluation of the c-spine OBJECTIVE For thirty years , emergency medical services agencies have emphasized limiting spinal motion during transport of the trauma patient to the emergency department . The long spine board ( LSB ) has been the mainstay of spinal motion restriction practice s , despite the paucity of data to support its use . The purpose of this study was to determine reduction in lateral motion afforded by the LSB in comparison to the stretcher mattress alone . METHODS This was a r and omized controlled crossover trial where healthy volunteer subjects were r and omly assigned to either LSB or stretcher mattress only . All subjects were fitted with a rigid cervical collar , secured to the assigned device ( including foam head blocks ) , and driven on a closed course with prescribed turns at a low speed ( < 20 mph ) . Upon completion , the subjects were then secured to the other device and the course was repeated . Each subject was fitted with 3 graduated-paper disks ( head , chest , hip ) . Lasers were affixed to a scaffold attached to the stretcher bridging over the patient and aim ed at the center of the concentric graduations on the disks . During transport , the degree of lateral movement was recorded during each turn . Significance was determined by t test . RESULTS In both groups , the head demonstrated the least motion with 0.46±0.4-cm mattress and 0.97±0.7-cm LSB ( P≤ .0001 ) . The chest and hip had lateral movement with chest 1.22±0.9-cm mattress and 2.22±1.4-cm LSB ( P≤ .0001 ) , and the hip 1.20±0.9-cm mattress and 1.88±1.2-cm LSB ( P≤ .0001 ) , respectively . In addition , lateral movement had a significant direct correlation with body mass index . CONCLUSION The stretcher mattress significantly reduced lateral movement during transport BACKGROUND To evaluate the practice s and outcomes associated with a statewide , emergency medical services ( EMS ) protocol for trauma patient spine assessment and selective patient immobilization . METHODS An EMS spine assessment protocol was instituted on July 1 , 2002 for all EMS providers in the state of Maine . Spine immobilization decisions were prospect ively collected with EMS encounter data . Prehospital patient data were linked to a statewide hospital data base that included all patients treated for spine fracture during the 12-month period following the spine assessment protocol implementation . Incidence of spine fractures among EMS-assessed trauma patients and the correlation between EMS spine immobilization decisions and the presence of spine fractures-stable and unstable-were the primary investigational outcomes . RESULTS There were 207,545 EMS encounters during the study period , including 31,885 transports to an emergency department for acute trauma-related illness . For this cohort , there were 12,988 ( 41 % ) patients transported with EMS spine immobilization . Linkage of EMS and hospital data revealed 154 acute spine fracture patients ; 20 ( 13.0 % ) transported without EMS-reported spine immobilization interventions . This nonimmobilized group included 19 stable spine fractures and one unstable thoracic spine injury . The protocol sensitivity for immobilization of any acute spine fracture was 87.0 % ( 95 % confidence interval [ CI ] , 81.7 - 92.3 ) with a negative predictive value of 99.9 % ( 95 % CI , 99.8 - 100 ) . CONCLUSIONS The use of this statewide EMS spine assessment protocol result ed in one nonimmobilized , unstable spine fracture patient in approximately 32,000 trauma encounters . Presence of the protocol affected a decision not to immobilize greater than half of all EMS-assessed trauma patients Objectives Rigid cervical collars are known to increase intracranial pressure ( ICP ) in severe traumatic brain injury ( TBI ) . Cerebral blood flow might decrease according to the Kellie Monroe doctrine . For this reason , the use of the collar in patients with severe TBI has been ab and oned from several trauma protocol s in the Netherl and s. There is no evidence on the effect of a rigid collar on ICP in patients with mild or moderate TBI or indeed patients with no TBI . As a first step we tested the effect in healthy volunteers with normal ICPs and intact autoregulation of the brain . Methods In this prospect i ve blinded cross-over study , we evaluated the effect of application of a rigid cervical collar in 45 healthy volunteers by measuring their optical nerve sheath diameter ( ONSD ) by transocular sonography . Sonographic measurement of the ONSD behind the eye is an indirect noninvasive method to estimate ICP and pressure changes . Results We included 22 male and 23 female volunteers . In total 360 ONSD measurements were performed in these 45 volunteers . Application of a collar result ed in a significant increase in ONSD in both the left ( & bgr;=0.06 , 95 % confidence interval : 0.05–0.07 , P<0.001 ) and the right eye ( & bgr;=0.01 , 95 % confidence interval : 0.00–0.02 , P=0.027 ) Conclusion Application of a rigid cervical collar significantly increases the ONSD in healthy volunteers with intact cerebral autoregulation . This suggests that ICP may increase after application of a collar . In healthy volunteers , this seems to be of minor importance . On the basis of our findings the effect of a collar on ONSD and ICP in patients with mild and moderate TBI needs to be determined Background : To date , the benefit of prehospital advanced life-support programs on trauma-related mortality and morbidity has not been established Methods : The Ontario Prehospital Advanced Life Support ( OPALS ) Major Trauma Study was a before – after systemwide controlled clinical trial conducted in 17 cities . We enrolled adult patients who had experienced major trauma in a basic life-support phase and a subsequent advanced life-support phase ( during which paramedics were able to perform endotracheal intubation and administer fluids and drugs intravenously ) . The primary outcome was survival to hospital discharge . Results : Among the 2867 patients enrolled in the basic life-support ( n = 1373 ) and advanced life-support ( n = 1494 ) phases , characteristics were similar , including mean age ( 44.8 v. 47.5 years ) , frequency of blunt injury ( 92.0 % v. 91.4 % ) , median injury severity score ( 24 v. 22 ) and percentage of patients with Glasgow Coma Scale score less than 9 ( 27.2 % v. 22.1 % ) . Survival did not differ overall ( 81.1 % among patients in the advanced life-support phase v. 81.8 % among those in the basic life-support phase ; p = 0.65 ) . Among patients with Glasgow Coma Scale score less than 9 , survival was lower among those in the advanced life-support phase ( 50.9 % v. 60.0 % ; p = 0.02 ) . The adjusted odds of death for the advanced life-support v. basic life-support phases were nonsignificant ( 1.2 , 95 % confidence interval 0.9–1.7 ; p = 0.16 ) . Interpretation : The OPALS Major Trauma Study showed that systemwide implementation of full advanced life-support programs did not decrease mortality or morbidity for major trauma patients . We also found that during the advanced life-support phase , mortality was greater among patients with Glasgow Coma Scale scores less than 9 . We believe that emergency medical services should carefully re-evaluate the indications for and application of prehospital advanced life-support measures for patients who have experienced major trauma BACKGROUND The purpose of this study was to prospect ively assess the sensitivity of clinical examination to screen for thoracolumbar spine ( TLS ) injury in awake and alert blunt trauma patients with distracting injuries . METHODS From December 2012 to June 2014 , all blunt trauma patients older than 13 years were prospect ively evaluated as per st and ard TLS examination protocol at a Level 1 trauma center . Awake and alert patients with Glasgow Coma Scale ( GCS ) score of 14 or greater underwent clinical examination of the TLS . Clinical examination was performed regardless of distracting injuries . Patients with no complaints of pain or tenderness on examination of the TLS were considered clinical ly cleared of injury . Patients with distracting injuries , including those clinical ly cleared and those with complaints of TLS pain or tenderness , underwent computed tomographic scan of the entire TLS . Patients with minor distracting injuries were not considered to have a distracting injury . RESULTS A total of 950 blunt trauma patients were entered , 530 ( 56 % ) of whom had at least one distracting injury . Two hundred nine patients ( 40 % ) with distracting injuries had a positive TLS clinical examination result , of whom 50 ( 25 % ) were diagnosed with TLS injury . Three hundred twenty-one patients ( 60 % ) with distracting injuries were initially clinical ly cleared , in whom 17 ( 5 % ) TLS injuries were diagnosed . There were no missed injuries that required surgical intervention , with only four injuries receiving TLS orthotic bracing . This yielded an overall clinical clearance sensitivity for injury of 75 % and sensitivity for clinical ly significant injury of 89 % . CONCLUSION In awake and alert blunt trauma patients with distracting injuries , clinical examination is a sensitive screening method for significant TLS injury . Radiologic assessment may be unnecessary for safe clearance of the asymptomatic TLS in patients with distracting injuries . These findings suggest significant potential reduction of both health care cost and patient radiation exposure . LEVEL OF EVIDENCE Diagnostic study , level IV ; therapeutic/care management study , level IV OBJECTIVES To explore the influence of risk factors present at Emergency Department admission on pressure ulcer development in trauma patients with suspected spinal injury , admitted to the hospital for evaluation and treatment of acute traumatic injuries . DESIGN Prospect i ve cohort study setting level one trauma center in the Netherl and s participants adult trauma patients transported to the Emergency Department on a backboard , with extrication collar and headblocks and admitted to the hospital for treatment or evaluation of their injuries . METHODS Between January and December 2013 , 254 trauma patients were included . The following dependent variables were collected : Age , Skin color and Body Mass Index , and Time in Emergency Department , Injury Severity Score , Mean Arterial Pressure , hemoglobin level , Glasgow Coma Score , and admission ward after Emergency Department . RESULTS Pressure ulcer development during admission was associated with a higher age ( p 0.00 , OR 1.05 ) and a lower Glasgow Coma Scale score ( p 0.00 , OR 1.21 ) and higher Injury Severity Scores ( p 0.03 , OR 1.05 ) . Extra nutrition decreases the probability of PU development during admission ( p 0.04 , OR 0.20 ) . Pressure ulcer development within the first 48h of admission was positively associated with a higher age ( p 0.01 , OR 1.03 ) and a lower Glasgow Coma Scale score ( p 0.01 , OR 1.16 ) . The proportion of patients admitted to the Intensive Care Unit and Medium Care Unit was higher in patients with pressure ulcers . CONCLUSIONS The pressure ulcer risk during admission is high in patients with an increased age , lower Glasgow Coma Scale and higher Injury Severity Score in the Emergency Department . Pressure ulcer risk should be assessed in the Emergency Department to apply preventive interventions in time BACKGROUND Most emergency transport protocol s in the United States currently call for the use of a spine board ( SB ) to help immobilize the trauma patient . However , there are concerns that their use is associated with a risk of pressure ulcer development . An alternative device , the vacuum mattress splint ( VMS ) has been shown by previous investigations to be a viable alternative to the SB , but no single study has explicated the tissue-interface pressure in depth . METHODS To determine if the VMS will exert less pressure on areas of the body susceptible to pressure ulcers than a SB we enrolled healthy subjects to lie on the devices in r and om order while pressure measurements were recorded . Sensors were placed underneath the occiput , scapulae , sacrum , and heels of each subject lying on each device . Three parameters were used to analyze differences between the two devices : 1 ) mean pressure of all active cells , 2 ) number of cells exceeding 9.3kPa , and 3 ) maximal pressure ( Pmax ) . RESULTS In all regions , there was significant reduction in the mean pressure of all active cells in the VMS . In the number of cells exceeding 9.3kPa , we saw a significant reduction in the sacrum and scapulae in the VMS , no difference in the occiput , and significantly more cells above this value in the heels of subjects on the VMS . Pmax was significantly reduced in all regions , and was less than half when examining the sacrum ( 104.3 vs. 41.8kPa , p<0.001 ) . CONCLUSION This study does not exclude the possibility of pressure ulcer development in the VMS although there was a significant reduction in pressure in the parameters we measured in most areas . These results indicate that the VMS may reduce the incidence and severity of pressure ulcer development compared to the SB . Further prospect i ve trials are needed to determine if these results will translate into better clinical outcomes |
13,597 | 27,007,113 | No serious adverse events were reported in the included trials with relation to aquatic exercise .
AUTHORS ' CONCLUSIONS There is moderate quality evidence that aquatic exercise may have small , short-term , and clinical ly relevant effects on patient-reported pain , disability , and QoL in people with knee and hip OA . | BACKGROUND Osteoarthritis is a chronic disease characterized by joint pain , tenderness , and limitation of movement .
At present , no cure is available .
Thus only treatment of the person 's symptoms and treatment to prevent further development of the disease are possible .
Clinical trials indicate that aquatic exercise may have advantages for people with osteoarthritis .
This is an up date of a published Cochrane review .
OBJECTIVES To evaluate the effects of aquatic exercise for people with knee or hip osteoarthritis , or both , compared to no intervention . | OBJECTIVE To compare the efficacy of aquatic exercise and a l and -based exercise programme vs control in patients with knee osteoarthritis . METHODS Primary outcome was change in pain , and in addition Knee Injury and Osteoarthritis Outcome Score question naire ( KOOS ) . St and ing balance and strength was also measured after and at 3-month follow-up . Seventy-nine patients ( 62 women ) , with a mean age of 68 years ( age range 40 - 89 years ) were r and omized to aquatic exercise ( n = 27 ) , l and -based exercise ( n = 25 ) or control ( n = 27 ) . RESULTS No effect was observed immediately after exercise cessation ( 8 weeks ) . At 3-month follow-up a reduction in pain was observed only in the l and -based exercise group compared with control ( -8.1 mm , ( 95 % confidence interval -15.4 to -0.4 ; p = 0.039 ) , but no differences between groups were observed for KOOS ; and no improvement following aquatic exercise . Eleven patients reported adverse events ( i.e. discomfort ) in l and -based exercise , while only 3 reported adverse events in the aquatic exercise . CONCLUSION Only l and -based exercise showed some improvement in pain and muscle strength compared with the control group , while no clinical benefits were detectable after aquatic exercise compared with the control group . However , aquatic exercise has significantly less adverse effects compared with a l and -based programme OBJECTIVE To conduct a preliminary investigation of the effects on floatation spa therapy on quality of life in patients with osteoarthritis to see if controlled trials are warranted . DESIGN Uncontrolled clinical trial . SETTING Private floatation spa therapy centre . PATIENTS Fourteen patients with chronic osteoarthritis of the weight-bearing joints , of whom four dropped out . INTERVENTION Six weekly sessions of floatation spa therapy . OUTCOME MEASURES SF36 , AIMS 2 and MYMOP quality -of-life question naires . MAIN RESULTS All patients improved . Differences between baseline and discharge scores showed statistically significant improvement for MYMOP , but not AIMS 2 or SF-36 . CONCLUSIONS Controlled trials of floatation spa therapy for patients with osteoarthritis are warranted BACKGROUND Balneotherapy , traditionally administered during a continuous stay at the Dead Sea area , has been shown to be effective for patients suffering from knee osteoarthritis . OBJECTIVES To evaluate the effectiveness of an intermittent regimen of balneotherapy at the Dead Sea for patients with knee osteoarthritis . METHODS Forty-four patients with knee osteoarthritis were included in a prospect i ve r and omized single-blind controlled study . The patients were divided into two groups : a treatment group ( n=24 ) , which were treated twice weekly for 6 consecutive weeks in a sulfur pool heated to 35 - 36 degrees C , and a control group ( n=20 ) treated in a Jacuzzi filled with tap water heated to 35 - 36 degrees C. Participants were assessed by the Lequesne index of osteoarthritis severity , the WOMAC index , the SF-36 quality of health question naire , VAS scales for pain ( completed by patients and physicians ) , and physical examination . RESULTS A statistically significant improvement , lasting up to 6 months , was observed in the treatment group for most of the clinical parameters . In the control group the only improvements were in the SF-36 bodily pain scale at 6 months , the Lequesne index at 1 month and the WOMAC pain score at the end of the treatment period . Although the patients in the control group had milder disease , the difference between the two groups was not statistically significant . CONCLUSIONS Intermittent balneotherapy appears to be effective for patients with knee osteoarthritis Objectives .To estimate cost and outcomes of the Arthritis Foundation aquatic exercise classes from the societal perspective . Design .R and omized trial of 20-week aquatic classes . Cost per quality -adjusted life year ( QALY ) gained was estimated using trial data . Sample size was based on 80 % power to reject the null hypothesis that the cost/QALY gained would not exceed $ 50,000 . Subjects and Methods . Recruited 249 adults from Washington State aged 55 to 75 with a doctor-confirmed diagnosis of osteoarthritis to participate in aquatic classes . The Quality of Well-Being Scale ( QWB ) and Current Health Desirability Rating ( CHDR ) were used for economic evaluation , supplemented by the arthritis-specific Health Assessment Question naire ( HAQ ) , Center for Epidemiologic Studies -Depression Scale ( CES-D ) , and Perceived Quality of Life Scale ( PQOL ) collected at baseline and postclass . Outcome results applied to life expectancy tables were used to estimate QALYs . Use of health care facilities was assessed from diaries/ question naires and Medicare reimbursement rates used to estimate costs . Nonparametric bootstrap sampling of costs/QALY ratios established the 95 % CI around the estimates . Results .Aquatic exercisers reported equal ( QWB ) or better ( CHDR , HAQ , PQOL ) health-related quality of life compared with controls . Outcomes improved with regular class attendance . Costs/QALY gained discounted at 3 % were $ 205,186 using the QWB and $ 32,643 using the CHRD . Conclusion .Aquatic exercise exceeded $ 50,000 per QALY gained using the community-weighted outcome but fell below this arbitrary budget constraint when using the participant-weighted measure . Confidence intervals around these ratios suggested wide variability of cost effectiveness of aquatic exercise To study the effect of thermal mineral water of Nagybaracska ( Hungary ) on patients with primary knee osteoarthritis in a r and omized , double-blind clinical trial , 64 patients with nonsurgical knee joint osteoarthritis were r and omly selected either into the thermal mineral water or into the tap water group in a non-spa resort village . The patients of both groups received 30-min sessions of bathing , 5 days a week for four consecutive weeks . The patients were evaluated by a blind observer immediately before and at the end of the trial using Western Ontario and McMaster Osteoarthritis ( WOMAC ) indices and follow-up assessment 3 months later . Twenty-seven patients of the 32 patients who received thermal mineral water and 25 of the 32 of those treated with tap water completed the trial . The WOMAC activity , pain , and total scores improved significantly in the thermal mineral-water-treated group . The improvement remained also at the end of the 3-month follow-up . The WOMAC activity , pain , and total scores improved significantly also in the tap water group at the end of the treatment course , but no improvement was detected at the end of the 3-month follow-up period . The treatment with the thermal mineral water of Nagybaracska significantly improved activity , pain , and total WOMAC scores of patients with nonsurgical OA of the knee . Even after 3 months , significant improvement was observed compared to the scores before the treatment or to tap water treatment Background and Purpose Aquatic physical therapy is frequently used in the management of patients with hip and knee osteoarthritis ( OA ) , yet there is little research establishing its efficacy for this population . The purpose of this study was to evaluate the effects of aquatic physical therapy on hip or knee OA . Subjects A total of 71 volunteers with symptomatic hip OA or knee OA participated in this study . Methods The study was design ed as a r and omized controlled trial in which participants r and omly received 6 weeks of aquatic physical therapy or no aquatic physical therapy . Outcome measures included pain , physical function , physical activity levels , quality of life , and muscle strength . Results The intervention result ed in less pain and joint stiffness and greater physical function , quality of life , and hip muscle strength . Totals of 72 % and 75 % of participants reported improvements in pain and function , respectively , compared with only 17 % ( each ) of control participants . Benefits were maintained 6 weeks after the completion of physical therapy , with 84 % of participants continuing independently . Discussion and Conclusion Compared with no intervention , a 6-week program of aquatic physical therapy result ed in significantly less pain and improved physical function , strength , and quality of life . It is unclear whether the benefits were attributable to intervention effects or a placebo response OBJECTIVE To examine the reliability of postural sway assessment in women with lower extremity arthritis and to ascertain the effects of an aquatic exercise intervention program on these measures . DESIGN The reliability of postural sway measures was analyzed by within-subjects ( Subject times Trial ) analysis of variance ( ANOVA ) . The effects of aquatic exercise were analyzed by repeated measures ANOVA using a planned comparison approach with an independent 2 x 2 ( Group times Test ) design . SETTING Testing in a motor control research laboratory ; aquatic exercise in a warm water pool at an area YMCA . PARTICIPANTS Volunteer sample , 24 women with lower extremity arthritis ( rheumatoid [ RA ] n = 11 , osteo [ OA ] n = 13 ) r and omly assigned into an aquatic exercise group ( n = 14 ) or control group ( n = 10 ) . INTERVENTION Postural sway measures under a two-legged stance test on two separate test days : day 1 , pretest ; day 2 , posttest , administered after a 6-week aquatic exercise program . RESULTS Reliability correlation coefficients for postural sway measures ranged from .64 to .94 for both subject groups . Aquatic exercise subjects significantly reduced lateral sway and total sway area scores ( by 18 % to 30 % ) under both visual conditions after the 6-week intervention . Postural sway scores were significantly higher under the no-vision condition than under the vision condition in each group for both test sessions . Both OA and RA groups had normal sagittal/lateral ratio scores . CONCLUSION Women with lower extremity arthritis can be reliably assessed on postural sway measures on a stable two-legged stance test . Although they had normal sagittal/lateral sway ratio scores ( ie , scores typical for nonarthritic peers ) , vision played an important role in their postural stability for this balance task . Aquatic exercise reduced postural sway in women with lower extremity arthritis , as demonstrated by a two-legged stance test , and this exercise program appears to be a viable treatment for increasing postural stability in this population CONTEXT R and omized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting ; however , generalizable data on drug safety reporting are sparse . OBJECTIVE To scrutinize the completeness of safety reporting in r and omized trials . DESIGN , SETTING , AND PATIENTS Survey of safety reporting in 192 r and omized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm ( N = 130074 patients ) . Trial reports were identified from comprehensive meta-analyses in 7 medical areas . MAIN OUTCOME MEASURES Adequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects ; article space allocated to safety reporting and predictors of such reporting . RESULTS Severity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39 % and 29 % of trial reports , respectively . Only 46 % of trials stated the frequency of specific reasons for discontinuation of study treatment due to toxicity . For these 3 parameters , there was significant heterogeneity in rates of adequate reporting across topics ( P = .003 , P<.001 , and P = .02 , respectively ) . Overall , the median space allocated to safety results was 0.3 page . A similar amount of space was devoted to contributor names and affiliations ( P = .16 ) . On average , the percentage of space devoted to safety in the results section was 9.3 % larger in trials involving dose comparisons than in those that did not ( P<.001 ) and 3.8 % smaller in trials reporting statistically significant results for efficacy outcomes ( P = .047 ) . CONCLUSIONS The quality and quantity of safety reporting vary across medical areas , study design s , and setting s but they are largely inadequate . Current st and ards for safety reporting in r and omized trials should be revised to address this inadequacy Previous research suggests that water exercise improves the activities of daily living ( ADL ) ability of the frail elderly , but the specific frequency and intensity of such programs is unclear . This study aims at comparing the effects of once- and twice-weekly water exercise on the ADL ability of frail elderly receiving nursing care for 2 years . The design is a prospect i ve r and omized longitudinal study . Participants were assigned to two different exercise groups ( Group 1 and Group 2 ) . Group 1 participated in a 60-min exercise session once a week , for 2 years , while Group 2 attended the session twice a week . Exercise sessions were divided into a 10-min warm-up on l and and 50 min of exercise in water . The 50-min water exercise program consisted of 20 min walking , 10 min ADL exercise , 10 min stretching and strength exercises , and 10 min relaxation in water . ADL ability and lower muscle strength were measured before the beginning of exercise and 6 months , 1 year , and 2 years after the program had started . Significant group differences occurred for bathing transfer and stair climbing at the 2-year measurement . These results suggested that at least twice-weekly water exercise was necessary to maintain the ADL ability and KEX of the frail elderly during the 1-year water exercise period and for one additional year afterward BACKGROUND Balneotherapy is an established treatment modality for musculoskeletal disease , but few studies have examined the efficacy of spa therapy in elderly patients with degenerative spine and joint diseases . OBJECTIVES To assess the effects of balneotherapy on chronic musculoskeletal pain , functional capacity , and quality of life in elderly patients with osteoarthritis of the knee or with chronic low back pain . METHODS The 81 patients in the study group underwent a 1 day course of 30 minute daily baths in mineral water . Changes were evaluated in the following parameters : pain intensity , functional capacity , quality of life , use of non-steroidal anti-inflammatory or analgesic drugs , subjective disease severity perceived by the patients , investigator-rated disease severity , and severity of pain perceived by the patients . We analyzed the results of 76 subjects as 5 did not complete the study . RESULTS Compared to baseline , all monitored parameters were significantly improved by balneotherapy in both investigated groups . Moreover , the favorable effect was prolonged for 3 months after treatment . CONCLUSIONS This study showed that balneotherapy is an effective treatment modality in elderly patients with osteoarthritis of the knee or with chronic low back pain , and its benefits last for at least 3 months after treatment BACKGROUND Aging compromises the ability of the central nervous system to maintain body balance and reduces the capacity for adaptive reactions . To prevent falls , the reception conditions for sensory information need to be improved . OBJECTIVES To evaluate the impact of a structured aquatic and a non-aquatic exercise program for lower-limb muscle endurance on the static and dynamic balance of elderly people . METHODS This was a prospect i ve r and omized clinical study in which the variables were assessed before and after the training program . Thirty-six elderly people were evaluated using four tests : the Berg Balance Scale , Dynamic Gait Index , gait speed and t and em gait . The participants were r and omized into three groups : aquatic exercise group , non-aquatic exercise group and control group . The exercise groups underwent a program for lower-limb muscle endurance that consisted of 40-minute sessions twice a week for six weeks . The participants were reevaluated after six weeks . The data were analyzed statistically using the univariate ANOVA test for comparisons between the groups before and after the intervention . RESULTS The program for lower-limb muscle endurance significantly increased balance ( p<0.05 ) in the evaluation tests after the training program . CONCLUSION The muscle endurance program provided a significant improvement in static and dynamic balance among community-dwelling elderly people . It was also possible to infer that this improvement occurred regardless of the environment , i.e. aquatic or non-aquatic . Article registered in the Australian New Zeal and Clinical Trials Registry ( ANZCTR ) under the number ACTRN 12609000780257 AIM The effectiveness of a water-based exercise ( WE ) program and a walking on l and ( WL ) program was evaluated in older women ( aged 62 - 65 years ) . METHODS Fifty healthy sedentary women were r and omly assigned to sedentary ( S ) , WE and WL groups . The two groups were exercised for 12 weeks at 70 % of the age-predicted maximum heart rate ( HR ) . The subjects were evaluated before and after the training period , and measurements of bodyweight , HR at rest , maximum aerobic power ( VO(2max ) mL/kg per min ) and neuromuscular performance ( upper and lower body strength ; agility ; upper and lower body flexibility ) were included . RESULTS After training , bodyweight was unchanged in both programs . The WE decreased the HR at rest by 10 % . Both WE and WL enhanced VO(2max ) by 42 % and 32 % , respectively . However , for the WE group the VO(2max ) values were significantly higher compared with the WL group ( P < 0.05 ) . All neuromuscular parameters improved after exercise , but only the WE group showed a significant improvement on the upper body strength and lower body flexibility . Besides , the upper and lower body strength and upper and lower body flexibility were significantly higher in the WE group compared with the WL group ( P < 0.05 ) , respectively . CONCLUSIONS Current results indicate that the WE and WL programs improved the cardiorespiratory and neuromuscular fitness of older women . Furthermore , when the effectiveness of the training programs were compared , it was verified that the WE program was more powerful in inducing changes in physical fitness versus the WL program Background Evidence exists demonstrating the benefits of exercise for people with osteoarthritis , but little is known about whether exercise programs are effective , that is , whether the benefits of exercise can be seen in “ real life ” programs for “ normal ” people under nonlaboratory conditions . Objective To identify characteristics of and outcomes for participants who adhere to a community-based aquatic exercise program . Method Two hundred and forty-nine adults with osteoarthritis were recruited from Washington State for r and omization to a 20-week Arthritis Foundation aquatic exercise program ( n = 125 ) or a wait-list control group ( n = 124 ) . Adherers were defined as those attending at least two classes per week for 16 of 20 weeks . Measures included : Quality of Well Being Scale , Health Assessment Question naire , Center for Epidemiological Studies -Depression Scale , and a single arthritis quality of life rating-item . Results Baseline to postintervention change scores revealed that treatment-group adherers ( N = 35 ) reported improved quality of well-being , physical function , and change in arthritis quality of life compared to controls ( N = 124 ) . When comparing treatment-group adherers ( N = 35 ) to treatment-group nonadherers ( N = 67 ) , quality of well-being and depressed mood improved for adherers , but not for nonadherers . Conclusion When analyzed for level of participation , exercise benefits adults with osteoarthritis . Consistent participation in exercise programs results in better outcomes . Improved methods are needed to enhance adherence , with increased attention to the role of intrinsic factors such as self-efficacy and belief systems OBJECTIVES To determine the efficacy of community water-based therapy for the management of lower limb osteoarthritis ( OA ) in older patients . DESIGN A pre-experimental matched-control study was used to estimate efficacy of water-based exercise treatment , to check design assumptions and delivery processes . The main study was a r and omised controlled trial of the effectiveness of water-based exercise ( treatment ) compared with usual care ( control ) in older patients with hip and /or knee OA . The latter was accompanied by an economic evaluation comparing societal costs and consequences of the two treatments . SETTING Water exercise was delivered in public swimming pools in the UK . Physical function assessment s were carried out in established laboratory setting s. PARTICIPANTS 106 patients ( 93 women , 13 men ) over the age of 60 years with confirmed hip and /or knee OA took part in the preliminary study . A similar , but larger , group of 312 patients ( 196 women , 116 men ) took part in the main study , r and omised into control ( 159 ) and water exercise ( 153 ) groups . INTERVENTIONS Control group patients received usual care with quarterly semi-structured telephone interview follow-up only . The intervention in the main study lasted for 1 year , with a further follow-up period of 6 months . MAIN OUTCOME MEASURES Pain score on the Western Ontario and McMaster Universities OA index ( WOMAC ) . Additional outcome measures were included to evaluate effects on quality of life , cost-effectiveness and physical function measurements . RESULTS Short-term efficacy of water exercise in the management of lower limb OA was confirmed , with effect sizes ranging from 0.44 [ 95 % confidence interval ( CI ) 0.03 to 0.85 ] on WOMAC pain to 0.76 ( 95 % CI 0.33 to 1.17 ) on WOMAC physical function . Of 153 patients r and omised to treatment , 82 ( 53.5 % ) were estimated to have complied satisfactorily with their treatment at the 1-year point . This had declined to 28 ( 18 % ) by the end of the 6-month follow-up period , during which support for the intervention had been removed and those wishing to continue exercise had to pay their own costs for maintaining their exercise treatment . High levels of co-morbidity were recorded in both groups . Nearly two thirds of all patients had a significant other illness in addition to their OA . Fifty-four control and 53 exercise patients had hospital inpatient episodes during the study period . Water exercise remained effective in the main study but overall effect size was small , on WOMAC pain at 1 year , a reduction of about 10 % in group mean pain score . This had declined , and was non-significant , at 18 months . Mean cost difference estimates showed a saving in the water exercise group of pound123 - -175 per patient per annum and incremental cost-effectiveness ratios ranged from pound3838 to pound5951 per quality -adjusted life-year ( QALY ) . Net reduction in pain was achieved at a net saving of pound135 - -175 per patient per annum and the ceiling valuation of pound580 - -740 per unit of WOMAC pain reduction was favourably low . CONCLUSIONS Group-based exercise in water over 1 year can produce significant reduction in pain and improvement in physical function in older adults with lower limb OA , and may be a useful adjunct in the management of hip and /or knee OA . The water-exercise programme produced a favourable cost -- benefit outcome , using reduction in WOMAC pain as the measure of benefit . Further research is suggested into other similar public health interventions . Investigation is also needed into how general practice can best be supported to facilitate access to participants for research trials in healthcare , as well as an examination of the infrastructure and workforce capacities for physical activity delivery and the potential extent to which healthcare may be supported in this way . More detailed research is required to develop a better underst and ing of the types of exercise that will work for the different biomechanical subtypes of knee and hip OA and investigation is needed on access and environmental issues for physical activity programmes for older people , from both a provider and a participant perspective , the societal costs of the different approaches to the management of OA and longer term trends in outcome measures ( costs and effects ) OBJECTIVE To compare the effects of a hydrotherapy resistance exercise programme with a gym based resistance exercise programme on strength and function in the treatment of osteoarthritis ( OA ) . DESIGN Single blind , three arm , r and omised controlled trial . SUBJECTS 105 community living participants aged 50 years and over with clinical OA of the hip or knee . METHODS Participants were r and omised into one of three groups : hydrotherapy ( n = 35 ) , gym ( n = 35 ) , or control ( n = 35 ) . The two exercising groups had three exercise sessions a week for six weeks . At six weeks an independent physiotherapist unaware of the treatment allocation performed all outcome assessment s ( muscle strength dynamometry , six minute walk test , WOMAC OA Index , total drugs , SF-12 quality of life , Adelaide Activities Profile , and the Arthritis Self-Efficacy Scale ) . RESULTS In the gym group both left and right quadriceps significantly increased in strength compared with the control group , and right quadriceps strength was also significantly better than in the hydrotherapy group . The hydrotherapy group increased left quadriceps strength only at follow up , and this was significantly different from the control group . The hydrotherapy group was significantly different from the control group for distance walked and the physical component of the SF-12 . The gym group was significantly different from the control group for walk speed and self efficacy satisfaction . Compliance rates were similar for both exercise groups , with 84 % of hydrotherapy and 75 % of gym sessions attended . There were no differences in drug use between groups over the study period . CONCLUSION Functional gains were achieved with both exercise programmes compared with the control group Spa therapy is frequently used in daily rheumatological practice , but its benefit remains to be evaluated . A prospect i ve r and omized controlled study was conducted in 1993 in patients with osteoarthritis of the hip , knee or lumbar spine . Treatment was either spa therapy at Vichy ( France ) of 3 weeks duration ( spa group ) or usual therapy ( control group ) . Assessment criteria were pain ( visual analogue scale ) , functional impairment ( Lequesne 's index for hip or knee disease , Main and Waddell 's for lumbar spinal diseases ) , quality of life index [ revised Arthritis Impact Measurement Scale ( AIMS 2 ) ] , and analgesic and /or non-steroidal anti-inflammatory drug ( NSAID ) consumption . Patients were included by r and omization into one of the two arms ( spa or control ) and assessment criteria were collected before spa therapy or the control period , and 3 and 24 weeks thereafter . A total of 188 patients ( lumbar spine 95 , knee 64 , hip 29 ) were included in the study ( spa group 91 , control group 97 ) . Changes in the assessment criteria after a 6 month follow-up period showed improvement in terms of pain , functional impairment and quality of life , with a reduced intake of symptomatic drugs ( NSAID and analgesic drugs ) in the spa group . This study suggests that spa therapy of 3 weeks duration has a prolonged , beneficial , symptomatic effect in osteoarthritis 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 AIMS The study aims to compare changes over time among three study groups on the primary outcome , pain , as well as on the secondary outcomes , other symptoms , activities of daily living function , sport and recreation function , knee-related quality of life , knee range of motions and the six-minute walk test and to investigate whether aquatic exercises would be superior compared with l and exercise on pain reduction . BACKGROUND Osteoarthritis is a prevalent musculoskeletal disorder . Appropriate exercise may prevent osteoarthritis-associated disabilities and increase life quality . To date , research that compares the effects of different types of exercise for knee osteoarthritis has been limited . DESIGN The study is a r and omised trial . METHODS Eighty-four participants with knee osteoarthritis were recruited from local community centres . Participants were r and omly assigned to the control , aquatic or l and -based exercise group . Exercise in both groups ran for 60 minutes , three times a week for 12 weeks . Data were collected at baseline , week 6 and week 12 during 2006 - 2007 . The instruments included the Knee Injury and Osteoarthritis Outcome Score , a st and ard plastic goniometer and the six-minute walk test . Generalised estimation equations were used to compare changes over time among groups for key outcomes . RESULTS Results showed statistically significant group-by-time interactions in pain , symptoms , sport/recreation and knee-related quality of life dimensions of Knee Injury and Osteoarthritis Outcome Score , knee range of motions and the six-minute walk test . However , the aquatic group did not show any significant difference from the l and group at both weeks 12 and 6 . CONCLUSIONS Both aquatic and l and -based exercise programmes are effective in reducing pain , improving knee range of motions , six-minute walk test and knee-related quality of life in people with knee osteoarthritis . The aquatic exercise is not superior to l and -based exercise in pain reduction . RELEVANCE TO CLINICAL PRACTICE Similar outcomes could be possible with the two programmes . Health care professionals may consider suggesting well- design ed aquatic or l and -based exercise classes for patients with osteoarthritis , based on their preferences and convenience OBJECTIVE To ascertain the effectiveness of the National Arthritis Foundation ( NAF ) aquatic and on-l and exercise programs on functional fitness and perceived ability to perform activities of daily living ( ADL ) measures in older adults with arthritis . DESIGN The effects of aquatic and on-l and exercise intervention programs were analyzed by repeated- measures analysis of variance by using a planned comparison approach with an independent 3 x 2 ( group by test ) design . omega(2 ) analyses were used to ascertain the relative treatment magnitude of each dependent variable . SETTING Testing in an indoor track facility ; exercise programs conducted in community setting s. PARTICIPANTS A volunteer sample of 30 men and women with arthritis ( osteoarthritis , n=22 ; rheumatoid arthritis , n=8 ) , r and omly assigned into either an aquatic exercise ( n=10 ) , on-l and exercise ( n=10 ) , or control group ( n=10 ) . INTERVENTION Eight-week on-l and and aquatic exercise program . MAIN OUTCOME MEASURES Functional fitness , ADLs , and h and -held dynamometry measures assessed on a 1-day pretest and posttest session , before and after an 8-week exercise program . RESULTS Aquatic and on-l and exercise subjects showed significant improvements on 9 of 12 functional fitness , 3 of 4 ADLs , and 7 of 8 h and -held isometric strength tests after their respective exercise programs . No significant changes were found in any of these measures for the control group . CONCLUSION Both NAF exercise programs appear to be effective in improving functional physical fitness and perceived ability to perform ADL measures in older adults with arthritis OBJECTIVE To evaluate the effects of moderate exercise on glycosaminoglycan ( GAG ) content in knee cartilage in subjects at high risk of knee osteoarthritis ( OA ) . METHODS Forty-five subjects ( 16 women , mean age 46 years , mean body mass index 26.6 kg/m(2 ) ) who underwent partial medial meniscus resection 3 - 5 years previously were r and omized to undergo a regimen of supervised exercise 3 times weekly for 4 months or to a nonintervention control group . Cartilage GAG content , an important aspect of the biomechanical properties of cartilage , was estimated by delayed gadolinium-enhanced magnetic resonance imaging of cartilage ( dGEMRIC ) , with results expressed as the change in the T1 relaxation time in the presence of Gd-DTPA ( T1[Gd ] ) . RESULTS Thirty of 45 patients were examined by dGEMRIC at baseline and followup . The exercise group ( n = 16 ) showed an improvement in the T1(Gd ) compared with the control group ( n = 14 ) ( 15 msec versus -15 msec ; P = 0.036 ) . To study the dose response , change in the T1(Gd ) was assessed for correlation with self-reported change in physical activity level , and a strong correlation was found in the exercise group ( n = 16 , r(S ) = 0.70 , 95 % confidence interval [ 95 % CI ] 0.31 - 0.89 ) and in the pooled group of all subjects ( n = 30 , r(S ) = 0.74 , 95 % CI 0.52 - 0.87 ) . CONCLUSION This in vivo cartilage monitoring study in patients at risk of knee OA who begin exercising indicates that adult human articular cartilage has a potential to adapt to loading change . Moderate exercise may be a good treatment not only to improve joint symptoms and function , but also to improve the knee cartilage GAG content in patients at high risk of developing OA PURPOSE The purpose of this study was to determine the physiological responses of elderly women to a well-rounded exercise program performed in water ( WEX ) . METHODS The participants ( 60 - 75 yr of age ) were r and omly divided into a training ( TR ) group ( N = 15 ) and a control group ( N = 15 ) . The TR group participated in a 12-wk supervised WEX program , 70 min x day(-1 ) , 3 d x wk(-1 ) . The WEX consisted of 20 min of warm-up and stretching exercise , 10 min of resistance exercise , 30 min of endurance-type exercise ( walking and dancing ) , and 10 min of cool-down exercise . RESULTS The WEX led to an increase ( P < 0.05 ) in peak VO2 ( 12 % ) and VO2 at lactate threshold ( 20 % ) . Muscular strength evaluated by a hydraulic resistance machine increased significantly at resistance dial setting 8 ( slow ) for knee extension ( 8 % ) , knee flexion ( 13 % ) , chest press ( 7 % ) and pull ( 11 % ) , shoulder press ( 4 % ) and pull ( 6 % ) , and back extension ( 6 % ) . Vertical jump ( 9 % ) , side-stepping agility ( 22 % ) , trunk extension ( 11 % ) , and FEV1.0 ( 7 % ) also increased significantly . There was a significant decrease in skin-fold thickness ( -8 % ) , low-density lipoprotein ( LDL ) cholesterol ( -17 % ) , and total cholesterol ( -11 % ) . There were no significant changes in these variables in the control group . CONCLUSION These results indicate that WEX elicits significant improvements in cardiorespiratory fitness , muscular strength , body fat , and total cholesterol in older adult women . Water-based exercise appears to be a very safe and beneficial mode of exercise that can be performed as part of a well-rounded exercise program BACKGROUND The patient acceptable symptom state ( PASS ) is the value beyond which patients can consider themselves well . This concept can help in interpreting results of clinical trials . OBJECTIVE To determine the PASS estimate for patients with knee and hip osteoarthritis ( OA ) by assessing pain , patient 's global assessment of disease activity , and functional impairment . METHODS A 4 week prospect i ve multicentre cohort study of 1362 out patients with knee or hip OA was carried out . Data on assessment of pain and patient 's global assessment of disease , measured on visual analogue scales , and functional impairment , measured on the Western Ontario McMaster Universities Osteoarthritis Index ( WOMAC ) function subscale , were collected at baseline and final visits . The patients assessed their satisfaction with their current state at the final visit . An anchoring method based on the patient 's opinion was used . RESULTS For patients with knee and hip OA , the estimates of PASS were , respectively , 32.3 and 35.0 mm for pain , 32.0 and 34.6 mm for patient global assessment of disease activity , and 31.0 and 34.4 points for WOMAC function score . The PASS varied moderately across the tertiles of baseline scores but not across age , disease duration , or sex . CONCLUSION The use of PASS in clinical trials would provide more meaningful results expressed as a proportion of patients in an acceptable symptom state OBJECTIVE To determine whether Tai Chi or hydrotherapy classes for individuals with chronic symptomatic hip or knee osteoarthritis ( OA ) result in measurable clinical benefits . METHODS A r and omized controlled trial was conducted among 152 older persons with chronic symptomatic hip or knee OA . Participants were r and omly allocated for 12 weeks to hydrotherapy classes ( n = 55 ) , Tai Chi classes ( n = 56 ) , or a waiting list control group ( n = 41 ) . Outcomes were assessed 12 and 24 weeks after r and omization and included pain and physical function ( Western Ontario and McMaster Universities Osteoarthritis Index ) , general health status ( Medical Outcomes Study Short Form 12 Health Survey [ SF-12 ] , version 2 ) , psychological well-being , and physical performance ( Up and Go test , 50-foot walk time , timed stair climb ) . RESULTS At 12 weeks , compared with controls , participants allocated to hydrotherapy classes demonstrated mean improvements ( 95 % confidence interval ) of 6.5 ( 0.4 , 12.7 ) and 10.5 ( 3.6 , 14.5 ) for pain and physical function scores ( range 0 - 100 ) , respectively , whereas participants allocated to Tai Chi classes demonstrated improvements of 5.2 ( -0.8 , 11.1 ) and 9.7 ( 2.8 , 16.7 ) , respectively . Both class allocations achieved significant improvements in the SF-12 physical component summary score , but only allocation to hydrotherapy achieved significant improvements in the physical performance measures . All significant improvements were sustained at 24 weeks . In this almost exclusively white sample , class attendance was higher for hydrotherapy , with 81 % attending at least half of the available 24 classes , compared with 61 % for Tai Chi . CONCLUSION Access to either hydrotherapy or Tai Chi classes can provide large and sustained improvements in physical function for many older , sedentary individuals with chronic hip or knee OA The purpose of the present study was to determine the effectiveness of a 24-week aquatic training ( AT ) program , which included both aerobic and resistance components , on muscle strength ( isometric and dynamic ) , flexibility , and functional mobility in healthy women over 60 years of age . Twenty-two subjects were assigned r and omly to either an AT ( n = 12 ) or a control ( C , n = 10 ) group . Volunteers participated in a supervised shallow-water exercise program for 60 minutes a day , 3 days a week ; the exercise program consisted of a 10-minute warm-up and stretching , 25 minutes of endurance-type exercise ( dancing ) at 80 % of heart rate (HR)max , 20 minutes of upper- and lower-body resistance exercises with specialized water-resistance equipment , and a 5-minute cool down . Maximal isometric torque of knee extensors ( KEXT ) and knee flexors ( KFLEX ) were evaluated by a Cybex Norm dynamometer , grip strength ( HGR ) was evaluated using a Jamar hydraulic dynamometer , and dynamic strength was evaluated via the 3 repetition maximum ( 3RM ) test for chest press , knee extension , lat pull down , and leg press . Jumping performance was evaluated using the squat jump ( SJ ) , functional mobility with the timed up- and -go ( TUG ) test , and trunk flexion with the sit- and -reach test . Body composition was measured using the bioelectrical impedance method . The AT induced significant improvements in KEXT ( 10.5 % ) and KFLEX ( 13.4 % ) peak torque , HGR strength ( 13 % ) , 3RM ( 25.7–29.4 % ) , SJ ( 24.6 % ) , sit- and -reach ( 11.6 % ) , and TUG ( 19.8 % ) performance . The AT group demonstrated a significant increase in lean body mass ( 3.4 % ) . No significant changes in these variables were observed in the C group . The results indicate that AT , with both aerobic and resistance components , is an alternative training method for improving neuromuscular and functional fitness performance in healthy elderly women AIM This paper reports a study of the effects of aquatic exercise on physical fitness ( flexibility , strength and aerobic fitness ) , self-reported physical functioning and pain in adults with osteoarthritis of the hip or knee . BACKGROUND Osteoarthritis is a common cause of disability and a primary reason for hip and knee joint replacement . Exercise is important for preventing and /or managing the functional limitations associated with joint disease . Aquatic exercise is thought to be beneficial and is often recommended for people with osteoarthritis ; however , few studies have examined the effects on people with osteoarthritis , and these have yielded inconsistent results . METHODS A two-group r and omized controlled trial with a convenience sample was used . Participants were recruited from community sources and r and omly assigned to a 12-week aquatic programme or a non-exercise control condition . Data for 38 participants were collected at baseline , week 6 , and week 12 during 2003 and 2004 . Instruments were a st and ard plastic goniometer , a h and held dynamometer , the 6-minute walk test , the multidimensional Health Assessment Question naire , and a visual analogue scale for pain . RESULTS Repeated measures analysis of variance showed that aquatic exercise statistically significantly improved knee and hip flexibility , strength and aerobic fitness , but had no effect on self-reported physical functioning and pain . The exercise adherence rate was 81.7 % , and no exercise-related adverse effect was observed or reported . CONCLUSIONS Beneficial short-term effects of aquatic exercise were found in adults with osteoarthritis of the hip or knee . Although the programme may not offer pain relief or self-reported improvements in physical functioning , results suggest that aquatic exercise does not worsen the joint condition or result in injury . Nurses engaging in disease management and health promotion for these patients should consider recommending or implementing aquatic classes for patients Abstract . The effects of thermal water from Cserkeszölö in Hungary were appraised in a r and omised , double blind study conducted on 58 patients with osteoarthritis of the knee . Balneotherapy was delivered as a 15-day course of 30-min daily sessions performed with thermal water ( active treatment ) or tap water of similar colour and odour ( placebo treatment ) . The musculoskeletal status of participants was evaluated at baseline , at the end of the balneotherapy course , and 3 months later . Study endpoints ( initial pain , range of motion , tenderness on palpation , stair climbing , physicians ' opinion and subjective rating by patients , and ambulation ) were assessed using visual analogue scales and symptom scores . Both groups improved ; however , the magnitude of improvement was significantly greater in patients treated with thermal water from Cserkeszölö A group of 120 patients with rheumatoid arthritis or osteoarthritis volunteered to be subjects for this study of aerobic versus nonaerobic exercise . Patients were stratified by diagnosis and r and omized into an exercise program of aerobic walking , aerobic aquatics , or nonaerobic range of motion ( controls ) . The retention rate for the 12-week program was 83 % . Exercise tolerance , disease-related measures , and self-reported health status were assessed . The aquatics and walking exercise groups showed significant improvement over the control group in aerobic capacity , 50-foot walking time , depression , anxiety , and physical activity after the 12-week exercise program . There were no significant between-group group differences in the change scores for flexibility , number of clinical ly active joints , duration of morning stiffness , or grip strength . Our findings document the feasibility and efficacy of conditioning exercise for people who have rheumatoid arthritis or osteoarthritis To investigate if spa water is superior to tap water ( TW ) in relieving the symptoms of pain , joint motion , life quality in knee osteoarthritis ( KOA ) patients . In this r and omized placebo-controlled trial , 52 patients with KOA were followed in two groups . In group I ( n = 27 ) , patients were treated in the pool full of spa water at 37 ° C for 20 min a day , 5 days a week , for a period of 2 weeks . In group II ( n = 25 ) , the same protocol was used but spa water was replaced by TW heated to 37 ° C . Patients in both groups were given a home-based st and ardized exercise program . Evaluation parameters were pain ( pVAS ) , tenderness score ( TS ) , 50-ft walking duration , quadriceps muscle strength ( QMS ) , active flexion degree ( AFD ) , WOMAC OA index , and Nottingham Health Profile ( NHP ) . The first evaluation was done after the informed consent was obtained . Second and third evaluations were done at the 2nd and 12th week . PVAS , 50-ft walking duration , AFD , TS , WOMAC , and NHP variables improved in group I. Same variables except QMS improved also in group II . Comparison of the groups just after treatment showed that only pVAS ( P = 0.015 ) , NHP pain score ( P = 0.020 ) , and TS ( P = 0.002 ) differed significantly in favor of group I at the 2nd or 12th week . Both of the thermal treatment modalities were found to be effective in the management of the clinical symptoms and quality of life in KOA patients . However , pain and tenderness improved statistically better with balneotherapy . There were no significant differences between the groups for the other variables Background and Purpose : This study was design ed to evaluate the effectiveness of hydrotherapy in subjects with osteoarthritis ( OA ) of the knee compared with subjects with OA of the knee who performed l and -based exercises . Subjects and Methods : Sixty-four subjects with OA of the knee were r and omly assigned to 1 of 2 groups that performed exercises for 18 weeks : a water-based exercise group and a l and -based exercise group . The outcome measures included a visual analog scale ( VAS ) for pain in the previous week , the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , pain during gait assessed by a VAS at rest and immediately following a 50-foot ( 15.24-m ) walk test ( 50FWT ) , walking time measured at fast and comfortable paces during the 50FWT , and the Lequesne Index . Measurements were recorded by a blinded investigator at baseline and at 9 and 18 weeks after initiating the intervention . Results : The 2 groups were homogenous regarding all parameters at baseline . Reductions in pain and improvements in WOMAC and Lequesne index scores were similar between groups . Pain before and after the 50FWT decreased significantly over time in both groups . However , the water-based exercise group experienced a significantly greater decrease in pain than the l and -based exercise group before and after the 50FWT at the week-18 follow-up . Discussion and Conclusion : Both water-based and l and -based exercises reduced knee pain and increased knee function in participants with OA of the knee . Hydrotherapy was superior to l and -based exercise in relieving pain before and after walking during the last follow-up . Water-based exercises are a suitable and effective alternative for the management of OA of the knee OBJECTIVES Knee osteoarthritis ( OA ) is a common chronic degenerative disorder . There are various treatment modalities . This study was planned to investigate the efficacy of balneotherapy , mud-pack therapy in patients with knee OA . METHODS A total of 80 patients with knee OA were included . Their ages ranged between 39 - 78 . The patients were separated in to three groups . Group I ( n=25 ) received balneotherapy , group II ( n=29 ) received mud-pack therapy and group III ( n=26 ) was hot-pack therapy group . The therapies were applied for 20 min duration , once a day , five times per week and a total of 10 session . Patients were assessed according to pain , functional capacity and quality of life parameters . Pain was assessed by using Visual Analogue Scale ( VAS ) and Western Ontario McMaster Osteoarthritis Index ( WOMAC ) pain scale ( 0 - 4 likert scale ) . Functional capacity was assessed by using WOMAC functional capacity and WOMAC global index . Quality of life was evaluated by Nottingham Health Profile ( NHP ) self-administered question naire . Also physician 's global assessment and the maximum distance that patient can walk without pain , were evaluated . The assessment parameters were evaluated before and after three months . RESULTS There were statistically significant improvement in VAS and WOMAC pain scores in group I ( p<0.001 ) , group II and III ( p<0.05 ) . The WOMAC functional and global index also decreased in group I ( p<0.05 ) , group II ( p<0.001 ) and hot-pack group ( p<0.05 ) . Quality of life results were significantly improved in balneotherapy and mud-pack therapy groups ( p<0.05 ) . No difference was observed in hot-pack therapy group ( p>0.05 ) . The maximum distance was improved both in group I and II ( p<0.05 ) but not in group III . Also physician 's global assessment was found to be improved in all groups ( p<0.05 ) . CONCLUSIONS Balneotherapy and mud-pack therapy were effective in treating patients with knee OA OBJECTIVE To compare the effects of concentric and coupled concentric-eccentric isokinetic resistance training on functional capacity and symptoms of patients with osteoarthrosis ( OA ) of both knees . DESIGN Repeated measures . SETTING A university exercise physiology laboratory . PARTICIPANTS Twenty-three volunteers , ages 41 to 75 years . Patients were r and omly assigned to 3 groups : concentric ( CON , n = 9 ) , concentric-eccentric ( CON-ECC , n = 8) , and nontreatment ( NONTX , n = 6 ) . INTERVENTIONS The CON group performed 12 concentric contractions of each knee extensor and flexor muscles ; the CON-ECC group performed 6 concentric and 6 eccentric contractions of each knee muscle group by using a spectrum of angular velocities ranging from 30 degrees/s to 180 degrees/s with 30 degrees/s intervals , for both sides , 3 days a week for 8 weeks . MAIN OUTCOME MEASURES Functional capacity ( rising from a chair , walking , stair climbing and descending ) and pain during rest and activities , peak torque , and cross-sectional area ( CSA ) of knee muscle groups of subjects were tested before and after training . RESULTS Both training groups showed marked decreases ( P < .001 ) in pain scores and increases ( P < .001 ) in functional capacity together with increases ( P < .05 - -.01 ) in peak torque and CSA of knee muscles . However , the NONTX group did not display these marked changes after the 8-week period . The results also indicated that concentric-eccentric training has a greater influence on functional capacity , especially stair climbing and descending , than that of concentric training when compared with NONTX group ; however , the improvements in pain measurements were better in the CON group compared with the CON-ECC group after the training . CONCLUSIONS The results suggest that with the isokinetic resistance training used in this study , it is possible to improve functional capacity and decrease pain in patients with OA of the knee . The results also showed that extensive training involving a high number of repetitions and eccentric contractions was safe , effective , and well tolerated for the patients with knee OA Forty-one patients with rheumatoid arthritis were treated for 2 weeks at a Tiberias spa hotel . R and omized into 2 groups , Group 1 received a combination of mineral baths and mud packs , and Group 2 had tap water baths only . Both groups had a significant but temporary improvement in Ritchie index . Group 1 showed a significant improvement in grip strength . No improvement was noticed in morning stiffness , 15 meter walk time and laboratory variables of disease activity in either group . Twelve patients with osteoarthritis ( OA ) received 2 weeks of treatment with mineral baths and mud packs . Statistically significant improvement for a period of 6 months was noticed in night pain , pain on passive motion , tenderness on palpation and in the index of severity of OA of the knee OBJECTIVES Several studies suggest a beneficial overall effect of spa therapy in chronic musculoskeletal diseases . The present open controlled study investigated the effects of spa therapy at Bourbonne-Les-Bains , France , in patients with hip or knee osteoarthritis or low back pain . PATIENTS AND METHODS In 1998 , 102 men and women older than 50 years were included in the study . All had low back pain or lower limb osteoarthritis , and none had contraindications to spa therapy . Quality of life was assessed three times at intervals of 4 weeks , twice before and once immediately after 3 weeks of spa therapy , using the Duke Health Profile ( five dimensions and five dysfunctions ) . RESULTS Mean age was 66.4 years , and 67 % of the patients were women . Quality of life was markedly decreased as compared to the population at large ( 1996 , CFES ) . The two pretreatment evaluations produced similar quality -of-life scores . Spa therapy was associated with significant improvements in overall quality of life ( P=0.004 ) , self-esteem ( P=0.009 ) , and pain ( P=0.01 ) . CONCLUSION These findings support those of other studies conducted in France and in other European countries . They indicate that patients report meaningful improvements in their quality of life after spa therapy OBJECTIVE To investigate physical function in patients with severe osteoarthritis ( OA ) of the knees during and after a general physical training program . DESIGN R and omized control trial , blinded observer , follow-up at 3 months and 1 year . SETTING Outpatient clinic . PATIENTS Consecutive sample of 25 patients ( 3 men , 22 women ) with OA of the knees according to the criteria of the American College of Rheumatology ( ACR ) . Two patients ( 8 % ) failed to complete the study . There were no withdrawals for adverse effects . INTERVENTION Twelve patients received training in groups of 6 , twice a week for 3 months . Training focused on general fitness , balance , coordination , stretching , and lower extremity muscle strength , and included a daily home exercise program . MAIN OUTCOME MEASURES Muscle strength across the knee ( extension and flexion ) , Algofunctional Index ( AFI ) , pain ( 0 to 10 point scale ) , walking speed , clinical findings . RESULTS Patients participated in 96 of 96 assessment s ( 100 % ) and in 218 of 280 training sessions ( 77.9 % ) . From baseline to 3 months , isokinetic quadriceps strength ( 30 degrees/sec ) improved 20 % ( confidence interval [ CI ] 2alpha = .05 , 8 % to 50 % ) in the least affected leg ; isometric strength improved 21 % . By 1 year , AFI had decreased 3.8 points ( CI2alpha = .05 , 1.0 to 7.0 ) , pain had decreased 2.0 points ( CI2alpha = 05 , 0.0 to 4.0 ) , and walking speed had increased 13 % ( CI2alpha = .05 , 4 % to 23 % ) . There was an increase in the frequency of palpable joint effusions ( p < .01 ) on the most affected side . Frequency of crepitus decreased on the least affected side ( p < .01 ) . CONCLUSIONS General physical training appears to be beneficial to patients with OA of the knee . As shown by the high compliance and low dropout frequency , such a program is feasible even in patients with severe OA of the knee Hydrotherapy for OA of the hip has rarely been evaluated in controlled studies . Forty-seven patients with OA of the hip were followed for 18 weeks . Patients were r and omly allocated either to a regimen of home exercises or to twice weekly hydrotherapy for 6 weeks in addition to home exercises . There was an improvement seen in both subjective and objective measures in both groups with treatment . There was no significant difference between the two groups . Response to treatment appeared independent of age , sex and radiological severity . We conclude that for most patients , a carefully grade d and supervised regimen of home exercises is beneficial and there is little benefit in adding hydrotherapy to this regimen This study compared the effects of preoperative physical therapy or general cardiovascular conditioning exercises with the routine procedure of no preoperative physical therapy on patients undergoing primary total knee replacement . Thirty patients were r and omly assigned to 1 of 3 groups . Group 1 was the control group . Group 2 participated in a physical therapy program design ed to strengthen the upper and lower limbs and improve knee range of motion . Group 3 participated in a cardiovascular conditioning program , consisting of arm ergometry , cycle ergometry , aquatic exercises , and aerobic activity . All patients were evaluated preoperatively and postoperatively using the Hospital for Special Surgery Knee Rating , the Arthritis Impact Measurement Scale , and the Quality of Well Being instrument . Both experimental groups tolerated their respective exercise protocol s extremely well . All 3 groups showed significant improvement postoperatively as measured by the Hospital for Special Surgery Knee Rating , the Arthritis Impact Measurement Scale and the Quality of Well Being measurement scales . However , neither type of preoperative exercise added to the degree of improvement after surgery at any of the postoperative evaluations Objective : To examine the effectiveness of a 12-month community-based water exercise programme on measures of self-reported health and physical function in people aged over 60 years old with knee-hip osteoarthritis ( OA ) . Design : A quasi-experimental design consisting of an exercise group and an age-matched control group . Setting : Public community swimming pool in Sheffield , UK . Subjects : One hundred and six community-dwelling sedentary older people , with confirmed knee-hip osteoarthritis , enrolled in an experimental controlled trial for 12 months . Sixty-six subjects in the exercise group were offered a water-exercise programme . Forty age-matched , nonexercising , ‘ control ’ subjects received monthly education material and quarterly telephone calls . Interventions : Participants in the exercise group were asked to attend two exercise sessions a week of 1 hour duration led by specially trained swimming instructors . Main measures : Primary outcome measure was the disease-specific Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) . Secondary outcomes included a battery of performance-based physical function tests . Results : Adherence to exercise averaged 70 % ( ±14 % ) over the year : 77 % of the exercising subjects and 89 % control subjects completed both pre- and post- outcome measures . After one year , participants in the exercise group experienced a significant improvement in physical function ( 4.0 ± 9.1 versus -0.4 ± 7.3 units ; 95 % confidence interval ( CI ) 0.96–7.96 , p < 0.05 ) and reduction in the perception of pain ( 1.3 ± 3.7 versus 0.2 ± 2.5 units ; 95 % CI -0.19 - 2.52 , p < 0.05 ) compared with the control group , as measured by the WOMAC Osteoarthritis Index . In addition , the exercise group performed significantly better in the ascending and descending stairs tests ( p < 0.05 ) , had significantly greater improvements in knee range of movement ( p < 0.01 ) and hip range of movements ( p < 0.005 ) . There were no significant differences in the two groups for quadriceps muscle strength and psychosocial well-being ( Arthritis Impact Measurement Scales 2 question naire ) . Conclusions : Older people with knee/hip osteoarthritis gained modest improvements in measures of physical function , pain , general mobility and flexibility after participating in 12 months of community-based water exercise Objectives : The aim of the study was to evaluate the therapeutic effect of electro-acupuncture ( EA ) and hydrotherapy , both in combination with patient education or with patient education alone , in the treatment of osteoarthritis in the hip . Methods : Forty-five patients , aged 42–86 years , with radiographic changes consistent with osteoarthritis in the hip , pain related to motion , pain on load , and ache were chosen . They were r and omly allocated to EA , hydrotherapy , both in combination with patient education , or patient education alone . Outcome measures were the disability rating index ( DRI ) , global self-rating index ( GSI ) , and visual analogue scale ( VAS ) . Assessment s were done before the intervention and immediately after the last treatment and 1 , 3 , and 6 months after the last treatment . Results : Pain related to motion and pain on load was reduced up to 3 months after last the treatment in the hydrotherapy group and up to 6 months in the EA group . Ache during the day was significantly improved in both the EA and hydrotherapy group up to 3 months after the last treatment . Ache during the night was reduced in the hydrotherapy group up to 3 months after the last treatment and in the EA group up to 6 months after . Disability in functional activities was improved in EA and hydrotherapy groups up to 6 months after the last treatment . Quality of life was also improved in EA and hydrotherapy groups up to 3 months after the last treatment . There were no changes in the education group alone . Discussion : In conclusion , EA and hydrotherapy , both in combination with patient education , induce long-lasting effects , shown by reduced pain and ache and by increased functional activity and quality of life , as demonstrated by differences in the pre- and post-treatment assessment The objective of this study was to test if spa therapy can play a role in the management of severe knee osteoarthritis ( OA ) . Twenty patients with radiologically and clinical ly severe knee OA were r and omly assigned into spa and drug therapy groups . Spa group ( n = 10 ) traveled to a spa town and stayed at a hotel for a 10-day spa therapy course . They followed a balneotherapy regimen including thermal pool baths at 37 ° C for 20 min two times daily . Drug therapy group ( n = 10 ) stayed at home and followed their individually prescribed drug therapy ( NSAIDs and paracetamol ) . Patients were assessed at baseline ( week 0 ) , after spa therapy at 2 weeks ( week 2 ) and during follow-up period at 12 ( week 12 ) and 24 ( week 24 ) weeks by a blinded investigator . Patients assessed with Lequesne algofunctional index ( LAFI ) , pain ( visual analogue scale , VAS ) , patient ’s and investigator ’s global evaluation ( VAS ) , ten-stairs stepping up and down time , 15 m walking time and three times squatting up and down time . Significant improvement in pain and LAFI scores were found at week 2 , week 12 and week 24 in the spa therapy group compared to baseline . Comparing the two group differences , spa therapy was superior to drug therapy in pain reduction and in physician ’s global assessment at all time points . This superiority was also found in LAFI scores and patients ’ global assessment s at week 12 and week 24 . A 10-day course of spa therapy may be beneficial in short- and medium-term up to 24 weeks by reducing pain and improving functional status and overall well-being in patients with severe knee OA and may be considered as an effective therapeutic tool for such patients in countries like Turkey where it is widely available and ( at least partly ) reimbursed OBJECTIVE To investigate the efficacy of a water-based exercise program specifically targeting balance to reduce falls risk and improve measures of balance and physical function in older adults with osteoarthritis ( OA ) . DESIGN R and omized controlled trial . SETTING Community . PARTICIPANTS Persons ( N=39 ; mean±SD age , 74±6y ; 26 women ) with mild to moderate OA and at risk for falling met study criteria , were measured at baseline , and were r and omly assigned to the intervention ( n=23 ) and control groups ( n=16 ) . INTERVENTIONS Water-based program ( 12wk , twice weekly ; intervention group ) or a time-matched computer training program ( control group ) . MAIN OUTCOME MEASURE The primary outcome was the short-form Physiological Profile Assessment ( PPA ) . Secondary outcomes included the Step Test , Timed Up and Go Test , Western Ontario and McMaster Universities OA Index ( Likert 3.0 version ) , Arthritis Impact Measurement Scales 2 , and Activity-specific Balance Confidence Scale . RESULTS No statistically significant between-group differences were found for any outcome measured ( n=35 ; 4 lost to follow-up ) . Within-group analysis indicated that Step Test results improved significantly in both groups ( mean change : control group , left leg , 2.07 ; 95 % confidence interval , 3.19-.95 ; P=.002 ; intervention group , 2.14 ; 95 % confidence interval , 3.20 - 1.08 ; P=.000 ) . Two PPA item scores ( reaction time , contrast sensitivity ) improved significantly ( 86.83 ; 95 % confidence interval , 9.86 - 163.79 ; P=.03 ; 1.43 ; 95 % confidence interval , 2.35-.50 ; P=.005 , respectively ) in the control group , result ing in a lower falls risk score . CONCLUSIONS Water-based exercise did not reduce falls risk in our sample compared with attending a computer skills training class . Our study is , to our knowledge , the first to compare water-based exercise in this population with a control group that attended a time-dose-equivalent seated community-based activity . Whether gaining computer skills and going out into the community twice weekly is adequate stimulus to reduce falls risk in people with OA requires further investigation OBJECTIVE To design an aquatic exercise ( AQE ) and l and -based exercise ( LBE ) program to enhance knee function and reduce body fat in patients with obesity and knee osteoarthritis and to investigate the effectiveness of AQE and LBE on body fat , functional fitness , and functional status . SETTING Outpatient clinic at a Seoul National University Bundang Hospital . PARTICIPANTS Obese patients with knee osteoarthritis were recruited from patients who visited the rehabilitation , orthopedic surgery , and geriatric outpatient clinics at the hospital . Study participants were limited to those who met the following criteria : body mass index more than 25 kg/m(2 ) , abdominal circumference more than 90 cm ( men ) or 85 cm ( women ) , clinical ly diagnosed osteoarthritis with Kellgren-Lawrence scale 2 or higher on radiographic studies , and independent ambulation state . METHODS Participants were r and omly allocated into 3 groups : AQE ( n = 26 ) , LBE ( n = 25 ) , and the control group ( n = 24 ) . Exercise interventions were conducted 3 times a week for 8 weeks . OUTCOME MEASURES Body fat analysis , brief pain inventory , Western Ontario and McMaster Universities ' osteoarthritis index , Short Form-36 question naire , and knee isokinetic tests were evaluated to assess changes in body fat composition , pain , physical function , and quality of life before and after the exercise program . RESULTS Although no significant difference was found in general characteristics among the 3 groups before exercise , body fat proportion in the AQE group decreased significantly ( mean + /- SD , from 34.4 + /- 4.7 to 33.3 + /- 4.7 ; P = .031 ) after intervention . The body mass index was slightly reduced after intervention , but it was not statistically significant . The AQE group showed significant improvements in pain , disability , and quality of life . Notably , the change in pain interference in the AQE group ( mean + /- SD , from 25.8 + /- 15.1 to 18.8 + /- 13.1 ; P = .009 ) was greater than that of the LBE group . Both exercise groups showed significant improvements in Western Ontario and McMaster Universities ' osteoarthritis index disability compared with the control group . CONCLUSIONS AQE had an advantage in controlling the interference with activity because of pain . AQE may be an effective tool for patients with obesity who have difficulties with active exercise due to knee osteoarthritis |
13,598 | 32,282,119 | DISCUSSION AND CONCLUSIONS Decreasing unrealistic side-effect expectations may lead to decreased experience of side-effects and increased adherence to medical interventions . | BACKGROUND Fear of side-effects can result in non-adherence to medical interventions , such as medication and chemotherapy .
Side-effect expectations have been identified as strong predictors of later perception of side-effects .
However , research investigating predictors of side-effect expectations is disparate .
OBJECTIVE To identify factors associated with side-effect expectations . | Objective : To assess whether the type of scale used ( scaling effects ) and the severity of outcome ( outcome severity ) influence patients ’ numerical interpretations of verbal probability expressions . Design : Cross-sectional survey of patients in a general medicine clinic . Setting : A university-based Department of Veterans Affairs Medical Center . Participants : 210 patients seen consecutively in a general medicine clinic . Measurements and results : The patients were r and omized to scale and health outcome ( complications of surgery ) . Two scales ( a long form and a short form ) were used to expressly allow patients to choose probabilities less than 1 % . The long form had a lower bound of “ < 1 out of 1,000,000 ” ; the short form had a lower bound of “ < 1 out of 1,000 . ” Two complications were used : “ death from anesthesia ” and “ severe pneumonia . ” In the context of being told that their surgeon believed that the chance the complication would occur was “ rare , ” patients were asked to give the numerical estimate of that chance . The values elicited on both scales were significantly different for the two outcomes , with the “ rare ” risk of death from anesthesia being characterized as less likely than the “ rare ” risk of severe pneumonia ( F=5.24 , p=0.023 ) . Linear regression and three-factor analysis of variance showed significant differences in the probabilities elicited for scale , outcome , and age , with older patients generally responding with higher probabilities than did younger patients . Conclusions : These findings suggest that the severity of the associated outcome and the scale used to elicit patients ’ numerical estimates of verbal probability expressions influence patients ’ quantitative interpretations of the verbal probability statement ; and older patients respond with higher probabilities of negative outcomes than do younger patients . Future studies must continue to explore whether verbal probability expressions are adequate for communicating medical risk to patients or whether patients should be provided with numerical estimates of frequency OBJECTIVES The study evaluated the interpretation of , and preferences for , numerical information on side-effect incidence when presented in three different formats . METHODS It used a controlled design , with participants allocated at r and om to receive one of the three formats . Participants were recruited via a pop-up window on the CancerHelp UK website . The sample comprised 129 website users , of whom 96 % were women and 86 % had cancer , who received frequency information on four side effects of tamoxifen , using one of three risk expressions ( percentages , e.g. ' affects 25 % of people ' ; frequencies , e.g. ' affects 1 in 4 people ' ; combined , e.g. ' affects 1 in 4 people ( 25 % ) ' ) . They then interpreted information on tamoxifen and its effect on health , and estimates of side-effect frequency , and then stated a preference from the three risk expression formats . KEY FINDINGS The results showed that the three formats did not influence participants ' ratings of the information or their side-effect estimates . However , more than half ( 53 % ) the participants preferred the combined ( frequency and percentage ) format . In conclusion , a combined risk expression format performed no worse than percentages or frequencies alone and was preferred by a majority . CONCLUSIONS The three risk expression formats did not differ in their effect on participants ' interpretations . However , the preferred format was the combined ( frequency and percentage ) risk expression OBJECTIVE The objective of this r and omized controlled trial was to evaluate the efficacy of presenting information on the risks of side effects from a medicine , presented in different formats . METHODS A r and omized , parallel-group , single-center controlled trial was conducted among adult users of a training pharmacy . The information was categorized into the following groups : verbal descriptors+percentage range , percentage range and absolute percentage . The main outcomes were gist underst and ing and verbatim underst and ing , classified either as adequate or inadequate . The analyses were performed using ANOVA and Pearson 's chi-square test . RESULTS A total of 393 participants were recruited from June to October 2015 . Adequate levels of gist underst and ing and verbatim underst and ing were respectively 65.6 % and 53.9 % for the verbal descriptors+percentage range ( n=128 ) , 63.4 % and 44.3 % for percentage range ( n=131 ) , and 62.3 % and 48.5 % for absolute percentage ( n=131 ) , with no statistically significant difference between the groups ( p=0.852 and p=0.299 , respectively ) . CONCLUSION The underst and ing of the information was similar in all three formats , but the percentages of adequate underst and ing were low . PRACTICAL IMPLICATION S The percentage of inadequate underst and ing demonstrated in this study indicates that alternative formats for reporting adverse reactions need to be evaluated Objective : To determine whether the use of verbal descriptors suggested by the European Union ( EU ) such as “ common ” ( 1–10 % frequency ) and “ rare ” ( 0.01–0.1 % ) effectively conveys the level of risk of side effects to people taking a medicine . Design : R and omised controlled study with unconcealed allocation . Participants : 120 adults taking simvastatin or atorvastatin after cardiac surgery or myocardial infa rct ion . Setting : Cardiac rehabilitation clinics at two hospitals in Leeds , UK . Intervention : A written statement about one of the side effects of the medicine ( either constipation or pancreatitis ) . Within each side effect condition half the patients were given the information in verbal form and half in numerical form ( for constipation , “ common ” or 2.5 % ; for pancreatitis , “ rare ” or 0.04 % ) . Main outcome measure : The estimated likelihood of the side effect occurring . Other outcome measures related to the perceived severity of the side effect , its risk to health , and its effect on decisions about whether to take the medicine . Results : The mean likelihood estimate given for the constipation side effect was 34.2 % in the verbal group and 8.1 % in the numerical group ; for pancreatitis it was 18 % in the verbal group and 2.1 % in the numerical group . The verbal descriptors were associated with more negative perceptions of the medicine than their equivalent numerical descriptors . Conclusions : Patients want and need underst and able information about medicines and their risks and benefits . This is essential if they are to become partners in medicine taking . The use of verbal descriptors to improve the level of information about side effect risk leads to overestimation of the level of harm and may lead patients to make inappropriate decisions about whether or not they take the medicine OBJECTIVE To determine whether the public has different expectations of nonprescription medications based on location of sale . DESIGN Cross-sectional , descriptive . SETTING Saskatoon , Saskatchewan , Canada , during the summer of 2003 . PARTICIPANTS 2,102 r and omly selected citizens . INTERVENTION Mail survey . MAIN OUTCOME MEASURES Differences in expectations for potency , safety , adverse effects , effectiveness , and package information of products sold in pharmacies versus convenience stores . RESULTS The response rate was 57.2 % . Most participants ( 81.2 % ) were aware that nonprescription medications could be purchased in convenience stores , but far fewer ( 42.3 % ) had done so . As one potential re source during purchases , pharmacists were held in reasonably high regard . Expectations with the greatest difference were of a merch and ising nature . Respondents expected pharmacies to have a better quality and selection of products and lower prices . For drug-related attributes , differences were minimal but statistically significant . CONCLUSION Location of sale does not appear to have any practical influence on consumer expectations of the drug-related attributes of nonprescription medications . Buyers of such products expect similar properties to be present regardless of location Abstract Background : All licensed medicines in the European Union must be provided with a Patient Information Leaflet that includes a list of all known side effects . Among patients who read the leaflet , the side effects section is the most often read . A UK government regulatory publication recommends providing medicine side effect risk information in a combined format , using verbal descriptors accompanied by numerical information . Objectives : This study , with users of an existing popular patient information website , investigates the effectiveness of presenting medicine side effect risk information in different forms . Design : Participants were r and omly allocated to one of the three formats for representing risk information ( verbal descriptors , e.g. ‘ common ’ ; absolute frequencies , e.g. ‘ less than 1 in 10 people ’ ; and a combination of verbal descriptors and frequency b and s , e.g. ‘ common ( affects less than 1 in 10 people ) ’ . Methods : Participants ( n= 187 ) were recruited from users of the Cancer Research UK patient information website . They were asked to imagine that they had to take a cancer treatment ( tamoxifen ) , estimate the risks of four side effects occurring , and complete Likert scales relating to their satisfaction with the information supplied and perceived likelihood of various outcomes . Results : Those in the absolute frequency format demonstrated greater accuracy in estimating the likelihood of having two of four side effects than the other two formats . They were also more accurate at estimating the likelihood of themselves or the average person having any side effect from taking tamoxifen . Participants in the absolute frequency format rated the risk to health from tamoxifen as lower than those in the other two formats , were more satisfied with the information they received than those in the verbal format , and felt there would be less impact of the information on tamoxifen use than those in the combined format . Conclusions : These findings fail to confirm that the recommended use of combined descriptors for medicine side effects is unequivocally superior to absolute frequency alone . They also add weight to the growing body of research highlighting the deficiencies in using verbal descriptors for conveying side effect risk , and the strength of using absolute frequency descriptors BACKGROUND : Several studies suggest that many parents and research participants have poor underst and ing of the elements of consent , particularly the risks and benefits . However , some data suggest that the format and framing of research risks and benefits may be an important determinant of subject underst and ing . We examined the effect of tabular and graphical presentation of risks and benefits on parents ' underst and ing of a research study . METHODS : Parents of children scheduled to undergo an elective surgical procedure ( n = 408 ) were r and omized to receive information about the risks and benefits of a sham study of postoperative pain control using text , tables , or pictographs and then completed a question naire to examine their gist ( essential ) and verbatim ( actual ) underst and ing of the information . Parent demographics were recorded and their literacy and numeracy skills measured . RESULTS : Parents r and omized to receive information using tables or pictographs had significantly ( P < 0.025 ) greater gist and verbatim underst and ing than did parents who received the information using st and ard text . Tables and pictographs were also superior to text in promoting underst and ing among parents with low numeracy and literacy skills . CONCLUSIONS : Many parents and patients have difficulty in assimilating and interpreting risk/benefit information for both research and treatment . This is due , in part , to the manner in which risks and benefits are communicated and to the literacy and numeracy abilities of the individual . The results of this study suggest a simple and practical method for enhancing underst and ing of risk/benefit statistics for parents with varying numeracy and literacy skills 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 Patients with cancer undergoing similar treatments experience variable severity and frequency of side effects not adequately explained by pharmacological mechanisms , suggesting psychological influence . OBJECTIVES First , this study aim ed to further examine the relationship between patients ' expectations of multiple chemotherapy-related toxicities and experiences . Second , this study aim ed to explore the impact of anxiety and cancer coping styles to aid in informing interventions to lessen such expectations . METHODS A total of 59 eligible , consenting patients with cancer rated their expectations of 20 chemotherapy toxicities on 100-point linear analogue self- assessment indicators before treatment and completed the Spielberger State Anxiety Inventory and the Mental Adjustment to Cancer scale . Patients then rated their experience of side effects after one chemotherapy session . RESULTS Regressions controlling primary treating nurse influence and patient performance status showed toxicity experience was significantly predicted by patient expectations of mood changes , bleeding , skin itchiness , hair loss , feeling tired , and sleep disturbance ( β=0.30 - 0.55 ) . Anxiety was significantly related to expectations of nervousness and mood changes ; the coping style Fighting Spirit showed no significant associations , whereas conversely , Anxious Preoccupation showed some degree of association with all 20 toxicities ( r=0.11 - 0.34 ) . CONCLUSION Findings support the growing contention that patient expectations influence experience , negatively impacting quality of life . As it is unethical to withhold treatment information , research into screening for at-risk patients and offering brief interventions to minimize Anxious Preoccupation could be one way to reduce overall side effect burden , perhaps in the case of many medical interventions There is a paucity of information regarding the optimal method of presenting risk/benefit information to parents of pediatric research subjects . This study , therefore , was design ed to examine the effect of different message formats on parents ' underst and ing of research risks and benefits . An Internet-administered survey was completed by 4,685 parents who were r and omized to receive risk/benefit information about a study of pediatric postoperative pain control presented in different message formats ( text , tables , and pictographs ) . Survey questions assessed participants ' gist and verbatim underst and ing of the information and their perceptions of the risks and benefits . Pictographs were associated with significantly ( p < .05 ) greater likelihood of adequate gist and verbatim underst and ing compared with text and tables regardless of the participants ' numeracy . Parents who received the information in pictograph format perceived the risks to be lower and the benefits to be higher compared with the other formats ( p < .001 ) . Furthermore , compared with text and tables , pictographs were perceived as more “ effective , ” “ helpful , ” and “ trustworthy ” in presenting risk/benefit information . These results underscore the difficulties associated with presenting risk/benefit information for clinical research but suggest a simple method for enhancing parents ' informed underst and ing of the relevant statistics OBJECTIVE To investigate the effectiveness of presenting medicine side effect risk information in different forms , including that proposed by UK guidelines [ [ 1 ] Medicines and Healthcare products Regulatory Agency . Always read the leaflet-Getting the best information with every medicine . ( Report of the Committee on Safety of Medicines Working Group on Patient Information ) . London : The Stationery Office , 2005 . ] . METHODS 134 Cancer Research UK ( CRUK ) website users were recruited via a ' pop-up ' . Using a 2x2 factorial design , participants were r and omly allocated to one of four conditions and asked to : imagine they had to take tamoxifen , estimate the risks of 4 side effects , and indicate a presentation mode preference . RESULTS Those presented with absolute frequencies demonstrated greater accuracy in estimating 2 of 4 side effects , and of any side effect occurring , than those presented with frequency b and s. Those presented with combined descriptors were more accurate at estimating the risk of pulmonary embolism than those presented with numeric descriptors only . CONCLUSION Absolute frequencies outperform frequency b and s when presenting side effect risk information . However , presenting such exact frequencies for every side effect may be much less digestible than all side effects listed under 5 frequency b and s. Combined numerical and verbal descriptors may be better than numeric only descriptors when describing infrequent side effects . PRACTICE IMPLICATION S Information about side effects should be presented in ways that patients prefer , and which result in most accurate risk estimates Prior to scheduled surgery , patients frequently experience particularly high levels of distress and expect a variety of postsurgery symptoms . Surgery patients who confront breast cancer are no exception . It has been suggested that such presurgery distress and response expectancies are predictive of postsurgery outcomes . To test the contribution of presurgery distress and expectancies to common postsurgery symptom outcomes ( pain , nausea , fatigue , and discomfort ) , 63 female patients undergoing breast cancer surgery were recruited to a prospect i ve study . Results indicated that presurgery distress uniquely contributed to patients ' postsurgery nausea , fatigue , and discomfort ; specific expectancies uniquely contributed to pain intensity , pain unpleasantness , and fatigue ( ps < .05 ) . Consistent with expectancy theory , associations between response expectancies and postsurgery outcomes were not due to presurgery distress The objective was to examine the way that cancer patients translate verbal descriptors of probability into numerical estimates . A list of words commonly used on consent forms to describe the likelihood for benefits or risks of therapies was provided to 100 cancer patients . Two formats , paper/pencil or computer , were used to provide the list of words . Two methods , magnitude estimation and linear analogue scaling , were used to obtain probability estimates for each word . In addition , two scenarios were developed to study ' context effects ' on numerical interpretations of verbal descriptions of probability . All patients provided numerical values for the words on two occasions , separated by one week , and two interviewers collected the data . Regardless of method or format , each word elicited widely variable numerical interpretations . An ANOVA model , including patient , word , interviewer , time , method and format , indicated that patient and interviewer produced major effects on probability estimates . Agreement between methods and across time was good . Paper/pencil and computer formats yielded similar results . Context effects did not appear to influence the numerical probabilities elicited by the 2 scenarios . It was concluded that , within this group of patients , there was no consensus about numerical meaning of a given word , and that interviewers can systematic ally influence numerical interpretations . There appears to be a great deal of ' noise ' in this particular line of communication between patients and health professionals Context Direct-to-consumer drug advertisements do not provide st and ardized information about the benefits and harms of drug therapies . Contribution These r and omized trials tested whether adding a drug facts box to consumer prescription advertisements improved consumer knowledge and judgment . The facts box showed numbers of outcomes , including adverse events , which might occur with 2 alternative drug therapies . Consumers given advertisements that included the box had more accurate perceptions of drug benefits and side effects than consumers given advertisements without the box . Implication A st and ardized table quantifying outcomes that might occur with different therapies improved consumer knowledge of drug benefits and side effects . The Editors Direct-to-consumer advertising surpasses all other efforts to alert the U.S. public about prescription drugs . Industry spent more than $ 5 billion on these ads in 2007 (1)more than twice the total U.S. Food and Drug Administration ( FDA ) budget ( 2 ) . Although the ads are often justified as serving an educational purpose , they generally fail to provide the most fundamental information consumers need to make informed decisions : data on how well the drug works . To address this problem , we developed a drug facts box , a 1-page summary of a drug 's benefit and side effects . The central information is provided in a table that shows the chance of various outcomes for people who do and do not take the drug . In previous studies , we showed that consumers underst and and value this information ( 3 , 4 ) . We performed 2 r and omized , controlled trials in nationally representative sample s of U.S. adults ( the target audience for direct-to-consumer advertising ) to test whether a drug facts box improves consumer knowledge and helps people make better choices . Methods Design We conducted 2 r and omized , controlled trials with the same basic design from October 2006 through April 2007 : the symptom drug box trial and the prevention drug box trial . We conducted a pair of trials because consumers generally face decisions about 2 categories of drugs : those taken to treat current symptoms and those taken to reduce the risk for future events ( prevention ) . In the symptom drug box trial , we used direct-to-consumer ads for drugs to treat heartburn , an outcome ( heartburn relief ) that is common and experienced directly . We chose to include a proton-pump inhibitor ( PPI ) and a histamine-2 (H2)blocker because both drugs are used to treat current symptoms of the same disease and have similar side effect profiles , but PPIs clearly outperform H2-blockers ; we could therefore assess whether the box helped consumers choose the superior drug . In the prevention drug box trial , we used advertisements for a statin and clopidogrel for secondary cardiovascular prevention . These drugs are used to reduce the risk for future events that are important but relatively rare ( heart attack and death ) , so absolute effects can only be small . The goal of this trial was to see whether the box improved the accuracy of consumers ' perceptions about drugs used to reduce cardiovascular risk . Figure 1 shows the ads used in each trial . Figure 1 . Advertisements given to trial participants . Appendix 1 and Appendix 2 provide full-size images of all 8 ads . PPI = proton-pump inhibitor . Supplement . Appendix 1 Supplement . Appendix 2 Committees for the protection of human subjects at Dartmouth Medical School and the University of Massachusetts approved the trials . Trial protocol s were registered with Clinical Trials.gov before recruitment began . Sample Selection Figure 2 summarizes participant flow into the study . Figure 2 . Study flow diagram . R and om-Digit Dialing Protocol The Center for Survey Research , University of Massachusetts ( who conducted both surveys ) , created 2 national , r and om-digit dial sample s , each with about 3000 telephone numbers . Trained interviewers used a st and ard protocol in which they called each telephone number at least 6 times ( different days , weeks , and times ) . Whenever someone answered , the interviewer explained that we are conducting an important study about how people feel about different ways to provide information about prescription drugs in advertising . English-speaking adults age 35 to 70 years in the household were invited to participate ( if > 1 adult was eligible , the computerwhich guided these screening interviewsr and omly selected one ) . R and omization and Mail Survey Protocol Participants were r and omly assigned to the drug box or control group by using a central computerized r and om-number generator ( to ensure allocation concealment ) and were mailed survey material s ( 2 drug ads , the survey , and a stamped return envelope ) plus a prepaid $ 10 incentive with a promise of an additional $ 10 upon survey completion . Participants were not told about the alternate survey form . Nonresponders received reminder postcards after 2 weeks , a replacement question naire after 4 weeks , a telephone call after 6 weeks , and a question naire after 8 weeks . Response Rates We used st and ard Association for Public Opinion Research methods to calculate overall response rates ( 5 ) . The numerator is completed surveys ( 231 symptom drug box trial participants [ 122 in the drug box group and 109 in the control group ] and 219 prevention drug box trial participants [ 111 in the drug box group and 108 in the control group ] ) . The denominator is individuals known to be eligible ( 289 in the symptom drug box trial and 290 in the prevention drug box trial ) plus an estimate of eligible individuals in households that could not be screened . In the symptom drug box trial , this number184was calculated by applying the 44.4 % eligibility fraction observed among screened households to the 414 unscreened households . The overall response rates were 49 % in the symptom drug box trial ( 231/[289 + 184 ] ) and 46 % in the prevention drug box trial ( 219/[290 + 182 ] ) . Completion rates were calculated by using completed surveys as the numerator and participants as the denominator . For the symptom drug box trial , the completion rate was 89 % ( 231/258 ) ; the drug box group had a higher completion rate than the control group ( 95 % [ 122/129 ] vs. 84 % [ 109/129 ] ; P= 0.010 ) . In the prevention drug box trial , the completion rate was 84 % ( 219/260 ) and did not differ between groups . Study Material s We modified actual drug ads by disguising the name of the drug and manufacturer to avoid preconceived notions that participants might hold . Appendix 1 and Appendix 2 include all material s. Ad Image Page All participants received the same ad image page ( the colorful front page ) . Participants in the symptom drug box trial received ads for an H2-blocker ( Amcid ) and a PPI ( Maxtor ) . In the prevention drug box trial , the ads were for a statin ( Concor ) and clopidogrel ( Pridclo ) . Second Page In both trials , the second page differed according to r and omization . For control participants , the second page was the actual ad 's brief summary : the drug label excerpt that the FDA requires in drug ads . The drug box groups received drug facts boxes . These boxes ( Figure 3 shows the Pridclo [ clopidogrel ] box ) include a descriptive section with basic drug information ( such as indications and other things to consider doing ) . The central element is a summary table of efficacy and side effects presented as the chance of various outcomes for people who do or do not take the drug . We completed the boxes by using data from individual trials because that is how the FDA approaches drug approval ; they do not use meta- analysis to judge efficacy . Figure 3 . Pridclo ( clopidogrel ) drug facts box . FDA = U.S. Food and Drug Administration . To find efficacy data for the boxes in the symptom drug box trial , we used the Cochrane Collaboration review ( 6 ) on short-term treatment of gastroesophageal reflux diseaselike symptoms to identify all placebo-controlled trials of PPIs and H2-blockers for empirical therapy . For each drug , we chose the largest of the trials with same outcome : sustained relief , which is no heartburn episodes for 3 consecutive days . To facilitate comparisons , we st and ardized the base rate of sustained relief by averaging the findings in the placebo groups of the 2 studies ( 23 % in the H2-blocker study [ 7 ] vs. 15 % in the PPI study [ 8 ] , yielding an average base rate of 19 % ) . We calculated the relative risk ( drug vs. placebo ) for sustained relief in the H2-blocker ( relative risk , 1.87 ) and PPI ( relative risk , 4.67 ) trials by using the observed findings . To get st and ardized rates , we multiplied the averaged placebo rate by each relative risk . To frame the outcome as the proportion of patients still having heartburn , we used the complement of these calculated rates . Side effect data for the drug boxes were abstract ed from the corresponding brief summaries ( given to control participants ) to ensure that both groups had access to similar information . Although many side effects are listed throughout the brief summary , the drug box includes only the most important and largest relative to placebo or other comparator ( organized into life-threatening and symptom categories ) to focus the reader 's attention and minimize cognitive burden . To find efficacy data for the boxes in the prevention drug box trial , we began with the currently approved label for clopidogrel ( 9 ) . The label cites a single trial supporting the use of clopidogrel for heart attack prevention : CAPRIE ( Clopidogrel vs. Aspirin in Patients at Risk of Ischemic Events ) ( 10 ) . To find a similar study for the statin ( in terms of sample size , high-risk population , and outcome of heart attack ) , we review ed a meta- analysis of cholesterol-lowering treatment ( 11 ) . We chose the Medical Research Council Heart Protection Study of simvastatin ( 12 ) . To facilitate comparisons , we st and ardized the base rates of heart attack and all-cause mortality by taking the average risk in the comparator groups of the 2 studies . To get the st and ardized risk in both drug groups , we multiplied the st and ardized OBJECTIVES Research into the provision of patient information has demonstrated that , under certain conditions , patients overestimate the risks of medicine side effects . Gigerenzer and Edwards ( 2004 ) argue that ' natural frequencies ' are a less confusing way of expressing risk information . Two experiments with users of an existing high profile patient information website , investigate the effectiveness of presenting medicine side-effect risk information in different forms . DESIGN In both experiments participants were r and omly allocated to one of the three conditions for representing risk information ( a form of ' natural frequency ' , percentages and verbal descriptors ) . METHOD Participants were recruited from users of the Cancer Research UK patient information website ( Cancer Help UK ) . In Experiment 1 , participants ( N=148 ) were asked to imagine that they had to take a chemotherapy drug ( Taxol ) and were asked to estimate the risks of two side-effects occurring . In Experiment 2 participants ( N=137 ) estimated the risk for three different side-effects occurring with the painkiller ibuprofen . RESULTS In both experiments , verbal descriptions led to significantly higher estimations of risk compared to the other two formats . There was some evidence that people given information as frequencies were more accurate in their estimates than those given percentage information . CONCLUSIONS These findings provide partial support for the advantages of a form of ' natural frequencies ' when presenting side-effects to patients . They also add weight to the growing body of research highlighting the deficiencies in using verbal descriptions of side-effect risk alone OBJECTIVE To examine the effects of using positive or negative frames to describe influenza vaccine benefits and side effects on patients ' expectations , decisions , decisional conflict , and reported side effects . METHODS 292 previously unimmunized patients with chronic respiratory or cardiac disease were r and omly assigned to receive benefit/risk information that was framed : ( 1 ) positively as the percentage who remain free of influenza and have no vaccine side effects , or ( 2 ) negatively as the percentage who acquire influenza and have vaccine side effects . Question naires elicited expectations , decisions , and decisional conflict . Vaccines were telephoned 3 days later for a self-report of local and systemic side effects and work absenteeism . RESULTS Both groups had similar immunization rates and decisional conflict scores . The positive frame group had lower and more realistic expectations of vaccine side effects , fewer systemic side effects , and less work absenteeism ( p < 0.05 ) . CONCLUSION In contrast to previous studies of health care workers , framing did not influence patients ' decisions , possibly due to the patients ' awareness of their higher risk of influenza complications and greater desire to follow recommendations . The common practice of using negative frames when describing probabilities of side effects may need to be reexamined , considering its deleterious influence on self-reported side effects and work absenteeism Several studies have shown that patients ' expectancies for the development of nausea following chemotherapy are robust predictors of that treatment-related side effect , and some studies have shown that interventions design ed to influence expectancies can affect patients ' reports of symptoms . In this r and omized , multicenter , Community Clinical Oncology Program trial , we investigated the effect of an expectancy manipulation design ed to reduce nausea expectancy on chemotherapy-induced nausea in 358 patients scheduled to receive chemotherapy treatment . Patients in the intervention arm received general cancer-related educational material plus specific information about the efficacy of ondansetron , specifically design ed to diminish nausea expectancy . Patients in the control arm received only the general cancer-related educational material . Nausea expectancy was assessed both prior to and following the educational intervention . We observed a significant reduction in nausea expectancy in the intervention group ( P=0.024 ) as compared to the control group ( P=0.34 ) . In the intervention group , patients ' expectations of nausea assessed prior to the intervention correlated significantly with average nausea ( r=0.27 , P=0.001 ) , whereas nausea expectancy assessed following the intervention did not ( r=0.1 , P=0.22 ) . Although the expectancy manipulation reduced patients ' reported expectations for the development of nausea , the occurrence of nausea was not reduced . Furthermore , post-intervention nausea expectancy compared to pre-intervention expectancy was less predictive of subsequent nausea . Explanations for these findings include the possibility that the expectancy manipulation was not strong enough , and the possibility that changing nausea expectancies does not change occurrence of nausea Background : Previous research demonstrated that providing qualitative and quantitative information in a “ drug facts box ” may help individuals underst and prescription drug information in print-based direct-to-consumer advertisements . The authors sought to determine whether qualitative , quantitative , or a combination thereof best communicates benefit and risk information . Methods : To replicate and extend previous research , the authors used simple quantitative drug information . A r and omized controlled study was conducted with 5067 Internet panelists with heartburn . Participants viewed a drug facts box with benefit and risk information that varied the presence or absence of qualitative summaries and absolute frequencies , percentages , and absolute differences . Measures included knowledge of drug benefits and risks , perceptions , and intentions . Results : Providing absolute frequencies and percentages most improved participants ’ drug knowledge and affected perceptions and intentions . Conclusions : The study findings suggest that , for simple drug information , adding absolute frequencies and percentages to direct-to-consumer advertisements may benefit consumers . Absolute differences and qualitative labels may not be needed BACKGROUND The study evaluated European Medicines Agency ( EMA ) recommendations on communicating frequency information on side-effect risk . METHODS The study used a 2 × 2 factorial trial , with r and om allocation of information about 10 side-effects of paclitaxel ( Taxol ) expressed using one of four formats . Recruitment was via the CancerHelpUK website . Information was conveyed using numerical frequency b and s ( e.g. ' may affect up to 1 in 10 people ' ) or combined verbal terms and numerical b and s ( e.g. ' common : may affect up to 1 in 10 people ' ) ; in addition , the risk qualifier verb was manipulated , with risks expressed either as ' will affect … ' or ' may affect … ' . Participants then made six side-effect frequency estimates indicated their satisfaction with the information and evaluated the side-effects : how bad ; how likely ; how risky to health ; and their influence on taking paclitaxel . RESULTS The sample comprised 339 people , of whom 37.5 % had cancer . The combined verbal and numerical risk expressions result ed in higher estimates of side-effects , four of which reached statistical significance ( P < 0.05 ) , and participants also said that side-effects would be more likely . Use of ' may affect ' or ' will affect ' did not result in differences in any estimates . CONCLUSIONS This is the first evaluation of the full range of combined verbal and numerical risk expressions recommended in EMA guidance ; it demonstrates that they can lead to significant risk overestimations when compared to numerical frequency b and s alone . The EMA should consider revising its guidance . Government agencies and professional bodies should be cautious about recommendations for risk communication in the absence of empirical evidence INTRODUCTION We aim ed to determine demographic predictors of parental vaccine safety and risk perceptions , and assess the relationship between the occurrence of children 's perceived adverse events following immunisation ( AEFI ) on parents ' opinions . METHODS Computer-assisted telephone interviews ( CATI ) were conducted in 2011 with a cross-sectional , r and om general population sample of rural and metropolitan residents in South Australia . Multivariate ordinal logistic regression analyses examined associations between parental vaccine safety attitudes and socio-demographic factors , adjusting for whether children had ever experienced a previous suspected AEFI . RESULTS Of 469 parents interviewed , 95 % were confident in vaccine safety in general , but almost half expressed concern for pre-licensure testing of vaccines . Of all parents , 41 % responded that at least one of their children had experienced an AEFI . Almost one third of the AEFI parent group indicated they reported their children 's symptoms to either a healthcare professional or the Department of Health . Parental acceptability of the risks of febrile convulsion and anaphylaxis were 73 % and 76 % respectively . Ordinal logistic regression analyses showed parents of children who had experienced a suspected AEFI were associated with greater concern for vaccine safety ( OR:0.53 , p≤0.01 ) and more were likely to expect either a mild or a serious AEFI . After adjusting for demographics , parental confidence in vaccine safety was significantly associated with higher levels of education ( OR:2.58 , p=0.01 ) and being born in Australia OR:2.30 , p=0.004 . Mothers , when compared with fathers , were less accepting of the two vaccine risks presented : febrile convulsion ( OR:0.57 , p=0.04 ) and anaphylaxis , ( OR:0.55 , p=0.04 ) . CONCLUSIONS Parents commonly perceive and report that their child has experienced an AEFI . In this group of parents the subsequent expectation of an AEFI and vaccine safety concerns may be heightened . Further research should investigate parental underst and ings of differentiating an expected event from an adverse event as this could inform immunization risk communication and consumer AEFI reporting strategies BACKGROUND Despite limited evidence , it is often asserted that natural frequencies ( for example , 2 in 1000 ) are the best way to communicate absolute risks . OBJECTIVE To compare comprehension of treatment benefit and harm when absolute risks are presented as natural frequencies , percents , or both . DESIGN Parallel-group r and omized trial with central allocation and masking of investigators to group assignment , conducted through an Internet survey in September 2009 . ( Clinical Trials.gov registration number : NCT00950014 ) SETTING National sample of U.S. adults r and omly selected from a professional survey firm 's research panel of about 30,000 households . PARTICIPANTS 2944 adults aged 18 years or older ( all with complete follow-up ) . INTERVENTION Tables presenting absolute risks in 1 of 5 numeric formats : natural frequency ( x in 1000 ) , variable frequency ( x in 100 , x in 1000 , or x in 10,000 , as needed to keep the numerator > 1 ) , percent , percent plus natural frequency , or percent plus variable frequency . MEASUREMENTS Comprehension as assessed by 18 questions ( primary outcome ) and judgment of treatment benefit and harm . RESULTS The average number of comprehension questions answered correctly was lowest in the variable frequency group and highest in the percent group ( 13.1 vs. 13.8 ; difference , 0.7 [ 95 % CI , 0.3 to 1.1 ] ) . The proportion of participants who " passed " the comprehension test ( ≥13 correct answers ) was lowest in the natural and variable frequency groups and highest in the percent group ( 68 % vs. 73 % ; difference , 5 percentage points [ CI , 0 to 10 percentage points ] ) . The largest format effect was seen for the 2 questions about absolute differences : the proportion correct in the natural frequency versus percent groups was 43 % versus 72 % ( P < 0.001 ) and 73 % versus 87 % ( P < 0.001 ) . LIMITATION Even when data were presented in the percent format , one third of participants failed the comprehension test . CONCLUSION Natural frequencies are not the best format for communicating the absolute benefits and harms of treatment . The more succinct percent format result ed in better comprehension : Comprehension was slightly better overall and notably better for absolute differences . PRIMARY FUNDING SOURCE Attorney General Consumer and Prescriber Education grant program , the Robert Wood Johnson Pioneer Program , and the National Cancer Institute |
13,599 | 28,588,464 | Conclusions : Despite the innate heterogeneity of the field of study , it has been possible to establish a series of links between the neural and cognitive aspects , particularly regarding attention , cognitive control , visuospatial skills , cognitive workload , and reward processing .
However , many aspects could be improved . | Background : Video gaming is an increasingly popular activity in contemporary society , especially among young people , and video games are increasing in popularity not only as a research tool but also as a field of study .
Many studies have focused on the neural and behavioral effects of video games , providing a great deal of video game derived brain correlates in recent decades .
There is a great amount of information , obtained through a myriad of methods , providing neural correlates of video games .
Objectives : We aim to underst and the relationship between the use of video games and their neural correlates , taking into account the whole variety of cognitive factors that they encompass . | Videogame play ( VGP ) has been associated with numerous preferred and non-preferred effects . However , the effects of VGP on the development of microstructural properties in children , particularly those associated with negative psychological consequences of VGP , have not been identified to date . The purpose of this study was to investigate this issue through cross-sectional and longitudinal prospect i ve analyses . In the present study of humans , we used the diffusion tensor imaging mean diffusivity ( MD ) measurement to measure microstructural properties and examined cross-sectional correlations with the amount of VGP in 114 boys and 126 girls . We also assessed correlations between the amount of VGP and longitudinal changes in MD that developed after 3.0±0.3 ( s.d . ) years in 95 boys and 94 girls . After correcting for confounding factors , we found that the amount of VGP was associated with increased MD in the left middle , inferior and orbital frontal cortex ; left pallidum ; left putamen ; left hippocampus ; left cau date ; right putamen ; right insula ; and thalamus in both cross-sectional and longitudinal analyses . Regardless of intelligence quotient type , higher MD in the areas of the left thalamus , left hippocampus , left putamen , left insula and left Heschl gyrus was associated with lower intelligence . We also confirmed an association between the amount of VGP and decreased verbal intelligence in both cross-sectional and longitudinal analyses . In conclusion , increased VGP is directly or indirectly associated with delayed development of the microstructure in extensive brain regions and verbal intelligence The n-back task was hypothesized to be a dual task , permitting the imposition of parametrically increasing attentional and working memory dem and s , while keeping constant the dem and s of an embedded matching subtask . Visual targets were presented for 200 ms every 2.2 s at pseudor and omly varying positions on a computer screen . Participants were required to remember the most recent 0 , 1 , 2 , or 3 positions and responded with a choice button push to whether the current target position matched the position presented n items previously . P300 peak latency was constant across n-back tasks , reflecting constant perceptual and cognitive dem and s of the matching subtask . P300 peak amplitude decreased with increasing memory load , reflecting reallocation of attention and processing capacity away from the matching subtask to working memory activity . These data support a dual-task nature of the n-back , which should be considered when employing this paradigm This study sought to determine whether playing a “ serious ” interactive digital game ( IDG ) – the Re-Mission videogame for cancer patients – activates mesolimbic neural circuits associated with incentive motivation , and if so , whether such effects stem from the participatory aspects of interactive gameplay , or from the complex sensory/perceptual engagement generated by its dynamic event-stream . Healthy undergraduates were r and omized to groups in which they were scanned with functional magnetic resonance imaging ( FMRI ) as they either actively played Re-Mission or as they passively observed a gameplay audio-visual stream generated by a yoked active group subject . Onset of interactive game play robustly activated mesolimbic projection regions including the cau date nucleus and nucleus accumbens , as well as a subregion of the parahippocampal gyrus . During interactive gameplay , subjects showed extended activation of the thalamus , anterior insula , putamen , and motor-related regions , accompanied by decreased activation in parietal and medial prefrontal cortex . Offset of interactive gameplay activated the anterior insula and anterior cingulate . Between-group comparisons of within-subject contrasts confirmed that mesolimbic activation was significantly more pronounced in the active playgroup than in the passive exposure control group . Individual difference analyses also found the magnitude of parahippocampal activation following gameplay onset to correlate with positive attitudes toward chemotherapy assessed both at the end of the scanning session and at an unannounced one-month follow-up . These findings suggest that IDG-induced activation of reward-related mesolimbic neural circuits stems primarily from participatory engagement in gameplay ( interactivity ) , rather than from the effects of vivid and dynamic sensory stimulation As video-game playing has become a ubiquitous activity in today 's society , it is worth considering its potential consequences on perceptual and motor skills . It is well known that exposing an organism to an altered visual environment often results in modification of the visual system of the organism . The field of perceptual learning provides many examples of training-induced increases in performance . But perceptual learning , when it occurs , tends to be specific to the trained task ; that is , generalization to new tasks is rarely found . Here we show , by contrast , that action-video-game playing is capable of altering a range of visual skills . Four experiments establish changes in different aspects of visual attention in habitual video-game players as compared with non-video-game players . In a fifth experiment , non-players trained on an action video game show marked improvement from their pre-training abilities , thereby establishing the role of playing in this effect The authors investigated the effect of action gaming on the spatial distribution of attention . The authors used the flanker compatibility effect to separately assess center and peripheral attentional re sources in gamers versus nongamers . Gamers exhibited an enhancement in attentional re sources compared with nongamers , not only in the periphery but also in central vision . The authors then used a target localization task to unambiguously establish that gaming enhances the spatial distribution of visual attention over a wide field of view . Gamers were more accurate than nongamers at all eccentricities tested , and the advantage held even when a concurrent center task was added , ruling out a trade-off between central and peripheral attention . By establishing the causal role of gaming through training studies , the authors demonstrate that action gaming enhances visuospatial attention throughout the visual field BACKGROUND AND OBJECTIVE Neuroimaging studies have demonstrated dysfunction in the brain reward circuit in individuals with online gaming addiction ( OGA ) . We hypothesized that virtual reality therapy ( VRT ) for OGA would improve the functional connectivity ( FC ) of the cortico-striatal-limbic circuit by stimulating the limbic system . METHODS Twenty-four adults with OGA were r and omly assigned to a cognitive behavior therapy ( CBT ) group or VRT group . Before and after the four-week treatment period , the severity of OGA was evaluated with Young 's Internet Addiction Scale ( YIAS ) . Using functional magnetic resonance imaging , the amplitude of low-frequency fluctuation ( ALFF ) and FC from the posterior cingulate cortex ( PCC ) seed to other brain areas were evaluated . Twelve casual game users were also recruited and underwent only baseline assessment . RESULTS After treatment , both CBT and VRT groups showed reductions in YIAS scores . At baseline , the OGA group showed a smaller ALFF within the right middle frontal gyrus and reduced FC in the cortico-striatal-limbic circuit . In the VRT group , connectivity from the PCC seed to the left middle frontal and bilateral temporal lobe increased after VRT . CONCLUSION VRT seemed to reduce the severity of OGA , showing effects similar to CBT , and enhanced the balance of the cortico-striatal-limbic circuit Cognitive control is defined by a set of neural processes that allow us to interact with our complex environment in a goal -directed manner . Humans regularly challenge these control processes when attempting to simultaneously accomplish multiple goals ( multitasking ) , generating interference as the result of fundamental information processing limitations . It is clear that multitasking behaviour has become ubiquitous in today ’s technologically dense world , and substantial evidence has accrued regarding multitasking difficulties and cognitive control deficits in our ageing population . Here we show that multitasking performance , as assessed with a custom- design ed three-dimensional video game ( NeuroRacer ) , exhibits a linear age-related decline from 20 to 79 years of age . By playing an adaptive version of NeuroRacer in multitasking training mode , older adults ( 60 to 85 years old ) reduced multitasking costs compared to both an active control group and a no-contact control group , attaining levels beyond those achieved by untrained 20-year-old participants , with gains persisting for 6 months . Furthermore , age-related deficits in neural signatures of cognitive control , as measured with electroencephalography , were remediated by multitasking training ( enhanced midline frontal theta power and frontal – posterior theta coherence ) . Critically , this training result ed in performance benefits that extended to untrained cognitive control abilities ( enhanced sustained attention and working memory ) , with an increase in midline frontal theta power predicting the training-induced boost in sustained attention and preservation of multitasking improvement 6 months later . These findings highlight the robust plasticity of the prefrontal cognitive control system in the ageing brain , and provide the first evidence , to our knowledge , of how a custom- design ed video game can be used to assess cognitive abilities across the lifespan , evaluate underlying neural mechanisms , and serve as a powerful tool for cognitive enhancement The ultimate goal of cognitive enhancement as an intervention for age-related cognitive decline is transfer to everyday cognitive functioning . Development of training methods that transfer broadly to untrained cognitive tasks ( far transfer ) requires underst and ing of the neural bases of training and far transfer effects . We used cognitive training to test the hypothesis that far transfer is associated with altered attentional control dem and s mediated by the dorsal attention network and trained sensory cortex . In an exploratory study , we r and omly assigned 42 healthy older adults to six weeks of training on Brain Fitness ( BF-auditory perception ) , Space Fortress ( SF-visuomotor/working memory ) , or Rise of Nations ( RON-strategic reasoning ) . Before and after training , cognitive performance , diffusion-derived white matter integrity , and functional connectivity of the superior parietal cortex ( SPC ) were assessed . We found the strongest effects from BF training , which transferred to everyday problem solving and reasoning and selectively changed integrity of occipito-temporal white matter associated with improvement on untrained everyday problem solving . These results show that cognitive gain from auditory perception training depends on heightened white matter integrity in the ventral attention network . In BF and SF ( which also transferred positively ) , a decrease in functional connectivity between SPC and inferior temporal lobe ( ITL ) was observed compared to RON-which did not transfer to untrained cognitive function . These findings highlight the importance for cognitive training of top-down control of sensory processing by the dorsal attention network . Altered brain connectivity - observed in the two training tasks that showed far transfer effects - may be a marker for training success The ability to remember and navigate spatial environments is critical for everyday life . A primary mechanism by which the brain represents space is through hippocampal place cells , which indicate when an animal is at a particular location . An important issue is underst and ing how the hippocampal place-cell network represents specific properties of the environment , such as signifying that a particular position is near a doorway or that another position is near the end of a corridor . The entorhinal cortex ( EC ) , as the main input to the hippocampus , may play a key role in coding these properties because it contains neurons that activate at multiple related positions per environment . We examined the diversity of spatial coding across the human medial temporal lobe by recording neuronal activity during virtual navigation of an environment containing four similar paths . Neurosurgical patients performed this task as we recorded from implanted microelectrodes , allowing us to compare the human neuronal representation of space with that of animals . EC neurons activated in a repeating manner across the environment , with individual cells spiking at the same relative location across multiple paths . This finding indicates that EC cells represent non-specific information about location relative to an environment 's geometry , unlike hippocampal place cells , which activate at particular r and om locations . Given that spatial navigation is considered to be a model of how the brain supports non-spatial episodic memory , these findings suggest that EC neuronal activity is used by the hippocampus to represent the properties of different memory episodes Video games contain elaborate reinforcement and reward schedules that have the potential to maximize motivation . Neuroimaging studies suggest that video games might have an influence on the reward system . However , it is not clear whether reward-related properties represent a precondition , which biases an individual toward playing video games , or if these changes are the result of playing video games . Therefore , we conducted a longitudinal study to explore reward-related functional predictors in relation to video gaming experience as well as functional changes in the brain in response to video game training . Fifty healthy participants were r and omly assigned to a video game training ( TG ) or control group ( CG ) . Before and after training/control period , functional magnetic resonance imaging ( fMRI ) was conducted using a non-video game related reward task . At pretest , both groups showed strongest activation in ventral striatum ( VS ) during reward anticipation . At posttest , the TG showed very similar VS activity compared to pretest . In the CG , the VS activity was significantly attenuated . This longitudinal study revealed that video game training may preserve reward responsiveness in the VS in a retest situation over time . We suggest that video games are able to keep striatal responses to reward flexible , a mechanism which might be of critical value for applications such as therapeutic cognitive training Internet gaming disorder ( IGD ) is a subtype of internet addiction disorder ( IAD ) , but its pathogenesis remains unclear . This study investigated brain function in IGD individuals using task-state functional magnetic resonance imaging ( fMRI ) . It is a prospect i ve study in 19 IGD individuals and 19 matched healthy controls . They all received internet videogame stimuli while a 3.0 T fMRI was used to assess echo planar imaging . Brain activity was analyzed using the Brain Voyager software package . Functional data were spatially smoothed using Gaussian kernel . The threshold level was positioned at 10 pixels , and the activation range threshold was set to 10 voxels . Activated brain regions were compared between the two groups , as well as the amount of activated voxels . The internet videogame stimuli activated brain regions in both groups . Compared with controls , the IGD group showed increased activation in the right superior parietal lobule , right insular lobe , right precuneus , right cingulated gyrus , right superior temporal gyrus , and left brainstem . There was a significant difference in the number of activated voxels between the two groups . An average of 1078 voxels was activated in the IGD group compared with only 232 in the control group . Internet videogame play activates the vision , space , attention , and execution centers located in the occipital , temporal , parietal , and frontal gyri . Abnormal brain function was noted in IGD subjects , with hypofunction of the frontal cortex . IGD subjects showed laterality activation of the right cerebral hemisphere Traditional neuroimaging studies have mainly focused on brain activity derived from a simple stimulus and task . Therefore , little is known about brain activity during daily operations . In this study , we investigated hemodynamic changes in the dorsal prefrontal cortex ( DPFC ) during video games as one of daily amusements , using near infrared spectroscopy technique . It was previously reported that oxygenated hemoglobin ( oxyHb ) in adults ' DPFC decreased during prolonged game playing time . In the present study , we examined whether similar changes were observed in children . Twenty children ( 7 - 14 years old ) participated in our study , but only 13 of them were eventually subject to analysis . They played one or two commercially available video games ; namely a fighting and a puzzle game , for 5 min . We used changes in concentration of oxyHb as an indicator of brain activity and consequently , most of the children exhibited a sustained game-related oxyHb decrease in DPFC . Decrease patterns of oxyHb in children during video game playing time did not differ from those in adults . There was no significant correlation between ages or game performances and changes in oxyHb . These findings suggest that game-related oxyHb decrease in DPFC is a common phenomenon to adults and children at least older than 7 years old , and we suggest that this probably results from attention dem and from the video games rather than from subject 's age and performance |
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