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The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

A cost-benefit analysis of a California county's back injury prevention program.

Back-related injuries have become a major health problem in the workplace , affecting as many as 35 percent of the work force and accounting for about 25 percent of all compensation cl aims . This study evaluates a back injury prevention program among employees in a northern California county in 1989 - 90 . Six divisions of the county government were selected for the study because they had the highest prevalence of back pain experienced and the most back-related injuries in recent years . Four of the six divisions were r and omly selected as the intervention group and the remaining two , the control group . Overall , 77 percent or 205 of the targeted employees in the intervention group participated in the study . The intervention group was given an identical health risk assessment ( HRA ) before and after the 1-year back injury prevention program that offered employees a combination of education , training , physical fitness activities , and ergonomic improvement . The control group was neither given the HRA nor offered the program . The back injury and cost data of both the control and intervention groups were collected before and after the 1-year intervention . The results showed a modest overall decline in back pain prevalence rates , but significant improvement in satisfaction and reduction in risky behaviors . Cost-benefit analysis showed the net benefit of introducing back injury prevention program was $ 161,108 , and the return on investment is 179 percent . Therefore , the study offers suggestive evidence for the initial benefits of a back injury prevention program and lends support to the widely held belief that health promotion in the workplace can reduce employee health risks , increase healthful behaviors and attitudes , and improve attitudes toward the employer organization . Whether such intervention will continue to reap benefits in future years depends , to a large extent , on a favorable work environment and the maintenance and continuation of positive behavioral changes

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

Comparison of classroom instruction and independent study in body mechanics.

This study was design ed to determine which method of instruction in body mechanics results in the higher subsequent use of the techniques taught . Two groups were formed from nursing personnel at a rural general medical-surgical hospital in the southwestern United States . Subjects from the direct care nursing staff were r and omly assigned to one of the two groups . One group attended two hours of classroom instruction in body mechanics , while the other completed an independent study module . Subjects were pre- and posttested using the Work-Related Body Mechanics Evaluation ( Carlton , 1987 ) while performing a st and ardized lifting task in the clinical setting . Using analysis of covariance , no significant differences were found in the posttest scores of the two groups

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

Teaching and Social Support: Effects on Knowledge, Attitudes, and Behaviors to Prevent Low Back Injuries in Industry

This study was funded in part by NIH grant AR36308 The authors thank the employees of the United States Postal Service and the American Postal Workers Union ( APWU ) , Boston Metro Area Local , and Maith and lers Local 301 for their help and cooperation ; therapists from the Department of Rehabilitation Services , Bngham and Women 's Hospital for help in training workers ; and Ms Nancy Tanner for

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

A controlled trial of an educational program to prevent low back injuries.

BACKGROUND Low back injuries are common and costly , accounting for 15 to 25 percent of injuries covered by workers ' compensation and 30 to 40 percent of the payments made under that program . The high costs of injury , the lack of effective treatment . and the evidence that there are behavioral risk factors have led to widespread use of employee education programs that teach safe lifting and h and ling . The effectiveness of those programs , however , has received little rigorous evaluation . METHODS We evaluated an educational program design ed to prevent low back injury in a r and omized , controlled trial involving about 4000 postal workers . The program , similar to that in wide use in so-called back schools , was taught by experienced physical therapists . Work units of workers and supervisors were trained in a two-session back school ( three hours of training ) , followed by three to four reinforcement sessions over the succeeding few years . Injured subjects ( from both the intervention and the control groups ) were r and omized a second time to receive either training or no training after their return to work . RESULTS Physical therapists trained 2534 postal workers and 134 supervisors . Over 5.5 years of follow-up , 360 workers reported low back injuries , for a rate of 21.2 injuries per 1000 worker-years of risk . The median time off from work per injury was 14 days ( range , 0 to 1717 ) ; the median cost was $ 204 ( range , zero to $ 190,380 ) . After their return to work , 75 workers were injured again . Our comparison of the intervention and control groups found that the education program did not reduce the rate of low back injury , the median cost per injury , the time off from work per injury , the rate of related musculoskeletal injuries , or the rate of repeated injury after return to work ; only the subjects ' knowledge of safe behavior was increased by the training . CONCLUSIONS A large-scale , r and omized , controlled trial of an educational program to prevent work-associated low back injury found no long-term benefits associated with training

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The secondary prevention of low back pain: a controlled study with follow-up

& NA ; The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem . A 2 × 3 repeated measures design was employed with 2 groups and 3 assessment periods . The treatment group received an intervention design ed to reduce current problems , but above all to prevent reinjury and minor pains from becoming chronic medical problems , and it included a physical and behavioral therapy package . The control group was placed on a waiting‐list . Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity , anxiety , sleep quality and fatigue ratings , observed pain behavior , activities , mood , and helplessness . These differences were generally maintained at the 6 month follow‐up . In addition , the treatment group broke a trend for increasing amounts of pain‐related absenteeism , while the control group did not . Taken as a whole , the results suggest that a secondary prevention program aim ed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The Influence of Prophylactic Orthoses on Abdominal Strength and Low Back Injury in the Workplace

This study was design ed to determine the effect of multimodal intervention and the prevention of back injury , and to evaluate the adverse side effects of using a lumbosacral corset in the workplace . Subjects were 90 male warehouse workers r and omly selected from over 800 employees at a grocery distribution center . Subjects were assigned to three groups : true controls , no back school , no brace orthoses ; back school only ; and back school plus wearing a custom molded lumbosacral orthosis . Comparisons of pre-testing and 6-month follow-up posttesting for abdominal strength , cognitive data , work injury incidence and productivity and use of health care services were evaluated . Controls and training-only group showed no changes in strength productivity or lost time . Orthoses and training-group showed no changes in strength productivity or accident rate ; however , they showed substantially less lost time . This study supports the concept of using education and prophylactic bracing to prevent back injury and reduce time loss . It appears that the use of intermittent prophylactic bracing has no adverse affects on abdominal muscle strength and may contribute to decreased lost time from work injuries

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

Primary Prevention of Back Symptoms and Absence from Work: A Prospective Randomized Study Among Hospital Employees

The personnel at a geriatric hospital were r and omized into two groups . One group was allowed to exercise during working hours to improve back muscle strength , endurance , and coordination . The other group did not participate in the exercise program and received no further advice or information . After 13 months , the training group had increased back muscle strength . One subject had been absent from work 28 days in the training group whereas 12 subjects had been absent 155 days from work because of low back pain in the control group ( P<0.004 ) . The back pain complaints and intensity of back pain in the training group also decreased in a statistically significant way . Every hour spent by the physiotherapist on the training group reduced the work absence among the participants by 1.3 days , result ing in a cost/benefit ratio greater than 10

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

How study design affects outcomes in comparisons of therapy. II: Surgical.

We analysed the results of 221 comparisons of an innovation with a st and ard treatment in surgery published in six leading surgery journals in 1983 to relate features of study design to the magnitude of gain . For each comparison we measured the gain attributed to the innovation over the st and ard therapy by the Mann-Whitney statistic and the difference in proportion of treatment successes . For primary treatments ( aim ed at curing or ameliorating a patient 's principal disease ) , an average gain of 0.56 was produced by 20 r and omized controlled trials . This was less than the 0.62 average for four non-r and omized controlled trials , 0.63 for 19 externally controlled trials , and 0.57 for 73 record review s ( 0.50 represents a toss-up between innovation and st and ard ) . For secondary therapies ( used to prevent or treat complications of therapy ) , the average gain was 0.53 for 61 r and omized controlled trials , 0.58 for eleven non-r and omized controlled trials , 0.54 for eight externally controlled trials , and 0.55 for 18 record review s. Readers of studies evaluating new treatments , particularly for primary treatments , may consider adjustment of the gain according to the study type

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The effects of body mechanics instruction on work performance.

Thirty food service workers were r and omly assigned to two groups ; one group received body mechanics instruction while the other did not . The application of the instruction was measured by evaluating the subjects ' use of body mechanics on a novel lifting and lowering task and during performance on the job . Results indicated that the group which received instruction performed significantly better on the novel task than the group that received no instruction . However , no significant difference between groups was found in performance in the work environment . The role of the occupational therapist in a work-related safety program is also discussed

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

Effects of an exercise program on sick leave due to back pain.

The purpose s of this study were to evaluate the effect of a weekly exercise program on short-term sick leave ( less than 50 days ) attributable to back pain and to determine whether changes in absenteeism were related to changes in cardiovascular fitness . Subjects were r and omly assigned to an exercise group ( n = 58 ) and a control group ( n = 53 ) . Sick leave attributable to back pain was determined in the intervention period of 1 1/2 years and a comparable 1 1/2-year period prior to the study . In the exercise group , the number of episodes of back pain and the number of sick-leave days attributable to back pain in the intervention period decreased by over 50 % . Absenteeism attributable to back pain increased in the control group . The decrease in sick leave in the exercise group was not accompanied by any change in cardiovascular fitness . Suggestions for establishing exercise programs are given

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

The effect of body mechanics instruction on work performance among young workers.

Thirty young workers ( aged 14 to 19 years ) employed as groundskeepers and custodians were r and omly assigned to two groups ; one group received body mechanics instruction and the other did not . The instruction focused on proper spinal alignment in the work environment . Instruction on low back pain began with one classroom session before the subjects ' first day of work and continued during employment with two on-site sessions . The effect of instruction was evaluated through the observation of body mechanics during actual work performance . The results of the study indicate that the group that received instruction performed significantly better than the control group . This paper also discusses the occupational therapist 's role in providing job-specific body mechanics instruction in the work environment as a primary method of preventing low back pain

The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain

A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Quality of life and hospital re-admission in patients with chronic obstructive pulmonary disease.

BACKGROUND There is some evidence that quality of life ( QOL ) in patients with chronic obstructive pulmonary disease ( COPD ) may predict clinical outcomes and use of re sources . This study examined whether QOL scores could prospect ively predict re-admission for COPD or death within 12 months of an original admission , and whether QOL scores predicted home nebuliser provision . METHODS The study was carried out in all acute medical wards of Aberdeen Royal Infirmary , Woodend and City Hospitals , Aberdeen over 12 months . A total of 377 patients admitted with an exacerbation of COPD were identified in this time , 111 of whom were not included in the study because they refused the interview or died before discharge . The remaining 266 patients completed the St George 's Respiratory Question naire ( SGRQ ) . Information on spirometric parameters , nebuliser provision at discharge , provision of domiciliary oxygen , and re-admission within 12 months was collected from patient notes . RESULTS The mean age of the patients was 68 years and 53 % were men . The mean ( SD ) forced expiratory volume in one second ( FEV1 ) was 38.8 (18.0)% predicted and forced vital capacity ( FVC ) was 58.9 (23.8)% predicted . Higher ( worse ) scores on the SGRQ were significantly related to re-admission for COPD in the next 12 months ( difference = 4.8 , 95 % CI 1.6 to 8.0 ) . Patients who were re-admitted and died from COPD did not differ in SGRQ scores from those who were re-admitted and survived for more than 12 months . Re-admission was not related to sex , age , or pulmonary function . One hundred and thirty eight patients did not have a home nebuliser before admission . Of these , 14 were provided with a home nebuliser at discharge . Patients provided with nebulisers had significantly worse SGRQ scores and worse FVC . The 41 patients given domiciliary oxygen did not differ in SGRQ or spirometric parameters . Logistic regression analysis of the three SGRQ subscales ( Symptom , Impact and Activity ) , adjusting for lung function , age and sex , showed that all three subscales were significantly related to hospital readmission and that Impact scores were related to nebuliser provision . Women did not differ from men in Symptom scores on the SGRQ but differed markedly on the Activity and Impact scales . CONCLUSIONS It is concluded that poor scores on the SGRQ , a QOL scale which measures patient distress and coping , are associated with re-admission for COPD and use of re sources such as nebulisers , independent of physiological measures of disease severity

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Structured exercise improves physical functioning in women with stages I and II breast cancer: results of a randomized controlled trial.

PURPOSE Self-directed and supervised exercise were compared with usual care in a clinical trial design ed to evaluate the effect of structured exercise on physical functioning and other dimensions of health-related quality of life in women with stages I and II breast cancer . PATIENTS AND METHODS One hundred twenty-three women with stages I and II breast cancer completed baseline evaluations of generic and disease- and site-specific health-related quality of life , aerobic capacity , and body weight . Participants were r and omly allocated to one of three intervention groups : usual care ( control group ) , self-directed exercise , or supervised exercise . Quality of life , aerobic capacity , and body weight measures were repeated at 26 weeks . The primary outcome was the change in the Short Form-36 physical functioning scale between baseline and 26 weeks . RESULTS Physical functioning in the control group decreased by 4.1 points , whereas it increased by 5.7 points and 2.2 points in the self-directed and supervised exercise groups , respectively ( P = .04 ) . Post hoc analysis showed a moderately large ( and clinical ly important ) difference between the self-directed and control groups ( 9.8 points ; P = .01 ) and a more modest difference between the supervised and control groups ( 6.3 points ; P = .09 ) . No significant differences between groups were observed for changes in quality of life scores . In a secondary analysis of participants stratified by type of adjuvant therapy , supervised exercise improved aerobic capacity ( + 3.5 mL/kg/min ; P = .01 ) and reduced body weight ( -4.8 kg ; P < .05 ) compared with usual care only in participants not receiving chemotherapy . CONCLUSION Physical exercise can blunt some of the negative side effects of breast cancer treatment , including reduced physical functioning . Self-directed exercise is an effective way to improve physical functioning compared with usual care . In participants not receiving chemotherapy , supervised exercise may increase aerobic capacity and reduce body weight compared with usual care

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Quality of life in patients with chronic obstructive pulmonary disease improves after rehabilitation at home.

We have developed a rehabilitation programme at home and have investigated its effects on quality of life ( QOL ) , lung function , and exercise tolerance in patients with chronic obstructive pulmonary disease ( COPD ) . We studied 43 patients with severe airflow obstruction : forced expiratory volume in one second ( FEV1 ) 1.3 + /- 0.4 l ( mean + /- SD ) , FEV1/inspiratory vital capacity ( IVC ) 37 + /- 7.9 % . After stratification , 28 patients were r and omly allocated in a home rehabilitation programme for 12 weeks . Fifteen patients in a control group received no rehabilitation . The rehabilitation group received physiotherapy by the local physiotherapist , and supervision by a nurse and a general practitioner . Quality of life was assessed by the four dimensions of the Chronic Respiratory Question naire ( CRQ ) . We found a highly significant improvement in the rehabilitation group compared to the control group for the dimensions dyspnoea , emotion , and mastery . Lung function showed no changes in the rehabilitation group . The exercise tolerance improved significantly in the rehabilitation group compared to the control group . The improvement in quality of life was not correlated with the improvement in exercise tolerance . Rehabilitation of COPD patients at home may improve quality of life ; this improvement is not correlated with an improvement in lung function and exercise tolerance

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Randomized comparison of four tools measuring overall quality of life in patients with advanced cancer.

PURPOSE We report on a clinical trial developed to compare four different instruments that provide overall quality -of-life ( QOL ) scores , ranging from a simple , one-item instrument to more detailed instruments . Two issues addressed were ( 1 ) Will QOL tools suffer from missing data when used in a community-based cooperative group setting ? , and ( 2 ) Are there additional data generated by a more detailed multiitem instrument over that provided by a single-item global QOL question ? MATERIAL S AND METHODS A four-arm r and omized trial was design ed to compare four instruments that provide overall QOL scores in patients with advanced colorectal cancer . Patients and physicians completed the single-item Spitzer Uniscale ( UNISCALE ) at baseline and monthly . Patients were r and omly assigned to complete , in addition , either the 22-item Functional Living Index-Cancer ( FLIC ) , the five-item Spitzer QOL index ( QLI ) , a picture-face scale ( PICT ) , or nothing else . RESULTS A total of 128 patients were r and omized . Greater than 90 % complete QOL data were obtained . There was strong correlation , concordance , and criterion-related validity among all four patient-completed tools . The UNISCALE had a greater decrease over time than did the FLIC ( P=.005 ) , which suggests a greater sensitivity ; the UNISCALE was similar to the QLI and the PICT in this regard . Physicians provided lower UNISCALE scores than patients . Results supported the hypothesis that QOL is prognostic for survival . CONCLUSION Patients can effectively complete QOL tools in a cooperative group setting with proper education of health care providers and patients . A simple single-item tool ( UNISCALE ) appears to be appropriate to obtain a measure of overall QOL

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Defining the minimum level of detectable change for the Roland-Morris questionnaire.

BACKGROUND AND PURPOSE The Rol and -Morris Question naire ( RMQ ) is a self-administered disability measure in which greater levels of disability are reflected by higher numbers on a 24-point scale . The RMQ has been shown to yield reliable measurements , which are valid for inferring the level of disability , and to be sensitive to change over time for groups of patients with low back pain . Little is known about the usefulness of this instrument in aiding decision making regarding individual patients . The purpose of this study was to determine the minimum level of detectable change when the RMQ is applied to individual patients . SUBJECTS The study sample consisted of 60 out patients with low back pain . METHODS The RMQ was administered at the subjects ' initial visit and again 4 to 6 weeks later . Conditional st and ard errors of measurement ( CSEMs ) were computed for initial and follow-up RMQ scores , and these values were used to estimate the minimum level of detectable change . Results . Minimum levels of detectable change at the 90 % confidence level varied from 4 to 5 RMQ points . CONCLUSION AND DISCUSSION The magnitude of CSEMs is sufficiently small to detect change in patients with initial scores in the central portion of the scale ( 4 - 20 RMQ points ) ; however , the magnitude is too large to detect improvement in patients with scores of less than 4 and deterioration in patients who have scores greater than 20

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Short- and long-term effects of outpatient rehabilitation in patients with chronic obstructive pulmonary disease: a randomized trial.

PURPOSE Pulmonary rehabilitation programs are effective in patients with severe chronic obstructive pulmonary disease ( COPD ) in the short term , but their long-term effects are not known . We investigated the short- and long-term effects of a 6-month outpatient rehabilitation program in patients with severe COPD . SUBJECTS AND METHODS One hundred patients were r and omly assigned to receive either an exercise training program that included cycling , walking , and strength training ( n = 50 ) or usual medical care ( n = 50 ) . Thirty-four patients in the training group were evaluated after 6 months ( end of training ) , and 26 were evaluated after 18 months of follow-up . In the control group , 28 patients were evaluated at 6 months and 23 after 18 months . We measured pulmonary function , 6-minute walking distance , maximal exercise capacity , peripheral and respiratory muscle strength , and quality of life ( on a 20 to 140-point scale ) , and estimated the cost-effectiveness of the program . RESULTS At 6 months , the training group showed improvement in 6-minute walking distance [ mean difference ( training - control ) of 52 m ; 95 % confidence interval ( CI ) , 15 to 89 m ] , maximal work load ( 12 W ; 95 % CI , 6 to 19 W ) , maximal oxygen uptake ( 0.26 liters/min ; 95 % CI , 0.07 to 0.45 liters/min ) , quadriceps force ( 18 Nm ; 95 % CI , 7 to 29 Nm ) , inspiratory muscle force ( 11 cm H(2)O ; 95 % CI , 3 to 20 cm H(2)O ) , and quality of life ( 14 points ; 95 % CI , 6 to 21 points ; all P < 0.05 ) . At 18 months all these differences persisted ( P < 0.05 ) , except for inspiratory muscle strength . For 6-minute walking distance and quality of life , the differences between the training group and controls at 18 months exceeded the minimal clinical ly-important difference . CONCLUSION Among patients who completed the 6-month program , outpatient training result ed in significant and clinical ly relevant changes in 6-minute walking distance , maximal exercise performance , peripheral and respiratory muscle strength , and quality of life . Most of these effects persisted 18 months after starting the program

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

What are minimal important changes for asthma measures in a clinical trial?

In this study , the perceptions of asthmatics to change in their disease was associated with observed changes in clinical asthma measures , in order to identify the threshold where changes in clinical asthma measures are perceivable by patients . The study included 281 asthmatic patients , aged 18 - 63 yrs , in a r and omized , placebo-controlled clinical trial of a leukotriene antagonist . Changes were related in : 1 ) asthma symptom scores ; 2 ) inhaled beta-agonist use ; 3 ) forced expiratory volume in one second ( FEV1 ) ; and 4 ) peak expiratory flow ( PEF ) to a global question that queried overall change in asthma since starting the study drug . Additional analyses examined differences in the group reporting minimal improvement by treatment ( active treatment versus placebo ) , sex and age groups . The average minimal patient perceivable improvement for each measure was : 1 ) -0.31 points for the symptom score on a scale of 0 - 6 ; 2 ) -0.81 puffs x day(-1 ) for inhaled beta-agonist use ; 3 ) 0.23 L for FEV1 ; and 4 ) 18.79 L x min(-1 ) for PEF . In general placebo-treated patients and older patients , who reported minimal improvement , experienced less mean improvement from baseline than active-treated patients and younger patients , who reported minimal improvement . Determining the minimal patient perceivable improvement value for a measure may be helpful to interpret changes . However , interpretation should be carried out cautiously when reporting a single value as a clinical ly important change

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Quality of life in patients with endoscopy-negative heartburn: reliability and sensitivity of disease-specific instruments

OBJECTIVES : Endoscopy-negative gastroesophageal reflux disease ( GERD ) lacks objective markers of disease severity . Evaluation of therapies for GERD must therefore rely on subjective measures , including patient self-report question naires , to measure the clinical effectiveness of therapeutic interventions . We aim ed to evaluate the previously vali date d Gastrointestinal Symptoms Rating Scale ( GSRS ) and the Quality of Life in Reflux and Dyspepsia ( QOLRAD ) question naires for reliability and responsiveness to change over time . METHODS : Patients ( n = 1143 ) with heartburn , but no esophagitis included in a r and omized clinical trial assessing the effectiveness of active treatment with proton pump inhibitors over 4 wk were evaluated . RESULTS : The test-retest reliability of both question naires over time was good to excellent ( GSRS 0.53–0.69 ; QOLRAD 0.65–0.76 ) , as was the responsiveness estimated by st and ardized response means ( GSRS reflux dimension , −1.43 ; QOLRAD 0.81–1.43 ) and effect sizes ( GRSR reflux dimension , −1.74 ; QOLRAD 0.82–1.56 ) . The relationship between improvement in the GSRS reflux dimension score and the amount of clinical benefit as estimated by the patients themselves ( based on the Overall Treatment Evaluation ) suggested a minimally clinical relevant change is 0.5 on the seven grade d scales applied . The importance rating indicated that an important change in the GSRS reflux dimension and the QOLRAD dimensions is equivalent to 1.0 , and a very important change to 1.5 . CONCLUSIONS : The GSRS and QOLRAD are valid question naires that are reliable and sensitive to change . Both question naires should be suitable for use in clinical trials of therapeutic interventions for patients with heartburn

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Using the standard error of measurement to identify important changes on the Asthma Quality of Life Questionnaire

Objectives : To establish a link between the minimal important difference ( MID ) and the st and ard error of measurement ( SEM ) for all responsive dimensions of the Asthma Quality of Life Question naire ( AQLQ ) . Methods : Secondary data analysis of baseline and follow-up interview data from 198 out patients with asthma enrolled in a r and omized controlled trial and receiving care at a major urban academic medical center 's general medicine clinics . Domain statistics for baseline and follow-up interviews were examined for the AQLQ . The baseline SEM values were compared with established AQLQ MID st and ards using weighted κ values . Results : One SEM identified the MID in responsive AQLQ dimensions . Weighted κ values ( 0.88–0.93 ) vali date d excellent agreement between these two criteria . Conclusion : This is the third study to support using one SEM to identify important individual change in health-related quality of life ( HRQoL ) measures . However , refinement of the process for determining a measure 's clinical ly meaningful differences is still needed to secure a link between the SEM and the identification of relevant HRQoL change over time

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Long term benefits of rehabilitation at home on quality of life and exercise tolerance in patients with chronic obstructive pulmonary disease.

BACKGROUND --Pulmonary rehabilitation has been shown to have short term subjective and objective benefits for patients with chronic obstructive pulmonary disease ( COPD ) . However , appropriately controlled studies have not previously been performed , nor have the benefits of different types of continuation programme for rehabilitation been investigated . Both these problems have been addressed in a single study of the long term effects of once monthly physiotherapy versus once weekly physiotherapy at home after a comprehensive home rehabilitation programme on quality of life and exercise tolerance in patients with COPD . METHODS --Thirty six patients with severe airways obstruction ( mean SD ) forced expiratory volume in one second ( FEV1 ) 1.3(0.4 ) 1 , FEV1/inspiratory vital capacity ( IVC ) 37.2(7.9)% ) were studied . Twenty three patients followed a rehabilitation programme at home for 18 months consisting of physiotherapy and supervision by a nurse and general practitioner . During the first three months all 23 patients visited the physiotherapist twice a week for a 0.5 hour session . Thereafter , 11 patients ( group A ) received a session of physiotherapy once weekly while 12 patients ( group B ) received a session of physiotherapy once a month . The control group C ( 13 patients ) received no rehabilitation at all . Quality of life was assessed by the Chronic Respiratory Question naire , exercise tolerance by the six minute walking distance , and lung function by FEV1 and IVC . Outcome measures were assessed at baseline and at three , six , 12 , and 18 months . RESULTS --Long term improvements in quality of life were found in patients in groups A and B , but not in those in group C compared with baseline , but these only reached significance in group B at all time points . Patients in group B had a higher quality of life than those in group C only at three and 12 months . There was a decrease in both six minute walking distance ( at 12 and 18 months ) and IVC ( at three , 12 , and 18 months ) in patients in group C compared with the baseline measurement . Between groups analysis showed no differences for six minute walking distance , FEV1 , and IVC . CONCLUSIONS --This study is the first to show that rehabilitation at home for three months followed by once monthly physiotherapy sessions improves quality of life over 18 months . The change in quality of life was not associated with a change in exercise tolerance

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Linking clinical relevance and statistical significance in evaluating intra-individual changes in health-related quality of life.

OBJECTIVE To compare the st and ard error of measurement ( SEM ) with established st and ards for clinical ly relevant intra-individual change in an evaluation of health-related quality of life . DESIGN Secondary analysis of data from a r and omized controlled trial . SUBJECTS Six hundred and five out patients with a history of cardiac problems attending the general medicine clinics of a major academic medical center . MEASURES Baseline and follow-up interviews included a modified version of the Chronic Heart Failure Question naire ( CHQ ) and the SF-36 . The SEM values corresponding to established st and ards for minimal clinical ly important differences ( MCIDs ) on the CHQ were determined . Individual change on the SF-36 was explored using the same SEM criterion . RESULTS One-SEM changes in this population corresponded well to the patient-driven MCID st and ards on all CHQ dimensions ( weighted kappas ( 0.87 ; P < 0.001 ) . The distributions of out patients who improved , remained stable , or declined ( defined by the one-SEM criterion ) were generally consistent between CHQ dimensions and SF-36 subscales . CONCLUSIONS The use of the SEM to evaluate individual patient change should be explored among other health-related quality of life instruments with established st and ards for clinical ly relevant differences . Only then can it be determined whether the one-SEM criterion can be consistently applied as a proxy for clinical ly meaningful change

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

What is a clinically meaningful change on the Functional Assessment of Cancer Therapy-Lung (FACT-L) Questionnaire? Results from Eastern Cooperative Oncology Group (ECOG) Study 5592.

To assess the impact of disease and treatment on patients with advanced non-small cell lung cancer ( NSCLC ) , we set out to determine a clinical ly meaningful change ( CMC ) on the Lung Cancer Subscale ( LCS ) and the Trial Outcome Index ( TOI ) of the Functional Assessment of Cancer Therapy-Lung ( FACT-L ) question naire . We used data from Eastern Cooperative Oncology Group study 5592 ( E5592 ) , a r and omized trial comparing three chemotherapeutic regimens in 599 advanced NSCLC patients . Patients completed the FACT-L at baseline ( pretreatment ) , 6 weeks , 12 weeks , and 6 months . Comparing across baseline performance status ( 0 vs. 1 ) , prior weight loss ( < 5 % vs. > or = 5 % ) , and primary disease symptoms ( < or = 1 vs. > 1 ) , LCS and TOI score differences ranged from 2.4 to 3.6 and 6.5 to 9.2 , respectively ( all Ps < .001 ) . Mean improvement in LCS score from baseline to 12 weeks was 2.4 points in patients who had responded to treatment versus 0.0 points in patients who had progressive disease . Twelve-week LCS change scores for patients progressing early were 3.1 points worse than those of patients progressing later ( mean = -1.2 vs.1.9 , respectively ) . Similarly , the average TOI change score from baseline to 12 weeks was -6.1 for patients who had progressive disease versus -0.8 points for patients who had responded to treatment . Twelve-week TOI change scores for patients progressing early ( mean = -8.1 ) were 5.7 points worse than those of patients progressing later ( mean = -8.1 vs. -2.4 , respectively ) . Analyses assuming nonr and om missing data result ed in slightly larger differences . Clinical ly relevant change scores were estimated as two to three points for the LCS and five to seven points for the TOI , setting upper limits for minimal CMCs . These values were comparable to suggested distribution-based criteria of a minimally important difference . These results support use of a two to three point change in the LCS and five to six point change on the TOI of the FACT-L as a CMC , and offer practical direction for inclusion of important patient-based endpoints in lung cancer clinical trials

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Measurement of fatigue. determining minimally important clinical differences.

The purpose was to determine the minimally important clinical difference ( MICD ) in fatigue as measured by the Profile of Mood States , Schwartz Cancer Fatigue Scale ( SCFS ) , General Fatigue Scale , and a 10-point single-item fatigue measure . The MICD is the smallest amount of change in a symptom ( e.g. , fatigue ) measure that signifies an important change in that symptom . Subjects rated the degree of change in their fatigue over 2 days on a Global Rating Scale . 103 patients were enrolled on this multisite prospect i ve repeated measures design . MICD was determined following established procedures at two time points . Statistically significant changes were observed for moderate and large changes in fatigue , but not for small changes . The scales were sensitive to increases in fatigue over time . The MICD , presented as mean change , for each scale and per item on each scale is : POMS = 5.6 , per item = 1.1 , SCFS = 5.0 , per item = 0.8 , GFS = 9.7 , per item = 1.0 , and the single item measure of fatigue was 2.4 points . This information may be useful in interpreting scale scores and planning studies using these measures

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Interpreting quality-of-life clinical trial data for use in the clinical practice of antihypertensive therapy.

The use of quality -of-life indices in therapeutic trials is gaining recognition as important outcome variables for evaluating the total impact of antihypertensive therapy . While the statistical significance of treatment differentials in quality -of-life indices has been well documented , their clinical relevance still remains unclear . The interpretation of clinical trial quality -of-life treatment differentials depends on a clear underst and ing of the normal variability in the index due to changes in day-to-day living and the relationship between the size of the differential and shifts in population responses . Using the results from a large-scale r and omized clinical trial on quality of life and antihypertensive therapy , a rationale for the interpretation of clinical trial results for use by the practicing clinician is presented

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Quality of life of women with urinary incontinence: further development of the incontinence quality of life instrument (I-QOL)

OBJECTIVES To report on the further development of the Incontinence Quality of Life Instrument ( I-QOL ) , a self-report quality of life measure specific to urinary incontinence ( UI ) , including its measurement model , responsiveness , and effect size . METHODS Incontinent female patients ( 141 with stress , 147 with mixed UI ) completed the I-QOL and comparative measures at screening , pretreatment , and four subsequent follow-up visits during participation in a multicenter , double-blind , placebo-controlled , r and omized trial assessing the efficacy of duloxetine . Psychometric testing followed st and ardized procedures . RESULTS Factor analysis confirmed an overall score and three subscale scores ( avoidance and limiting behaviors , psychosocial impacts , and social embarrassment ) . All scores were internally consistent ( alpha = 0.87 to 0.93 ) and reproducible ( ICC = 0.87 to 0.91 ) . The pattern of previously reported correlations with the Short-Form 36-item Health Survey and Psychological Well-Being Schedule were confirmed . Responsiveness statistics using changes in the independent measures of stress test pad weight , number of incontinent episodes , and patient global impression of improvement ranged from 0.4 to 0.8 . Minimally important changes ranged from 2 % to 5 % in association with these measures and effect sizes . CONCLUSIONS In a clinical trial , the I-QOL proved to be valid , reproducible , and responsive to treatment for UI in women

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Minimal clinically important rehabilitation effects in patients with osteoarthritis of the lower extremities.

OBJECTIVE To estimate minimal clinical ly important differences ( MCID ) of effects measured by the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) in patients with osteoarthritis ( OA ) of the lower extremities undergoing a comprehensive inpatient rehabilitation intervention . METHODS A prospect i ve cohort study assessed patients ' health by the WOMAC at baseline ( entry into the clinic ) and at the 3 month followup , and by a transition question naire asking about the change of " health in general related to the OA joint " during that time period . The WOMAC section score differences between the " equal " group and the " slightly better " and " slightly worse " groups result ed in the MCID for improvement and for worsening . RESULTS In total 192 patients were followed up . The MCID for improvement ranged from 0.80 to 1.01 points on the continuous WOMAC numerical rating scale from 0 to 10 , reflecting changes of 17 to 22 % of baseline scores . The MCID for worsening conditions ranged from 0.29 ( 6 % ) to 1.03 points ( 22 % ) . In the transition reply subjectively unchanged patients reported a " pessimistic bias " of 0.35 to 0.51 points , except for the stiffness section . Both MCID and pessimistic bias showed regression to the mean and baseline dependency . CONCLUSION The assessment of MCID using the transition method is a heuristic and valid strategy to detect particular rehabilitation effects in patients with OA of the lower extremities with the use of the WOMAC , and it is worth implementing . The size of the MCID and of the systematic bias is comparable to that assessed by other methods and in other therapeutic setting

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Smallest detectable and minimal clinically important differences of rehabilitation intervention with their implications for required sample sizes using WOMAC and SF-36 quality of life measurement instruments in patients with osteoarthritis of the lower extremities.

OBJECTIVE To discuss the concepts of the minimal clinical ly important difference ( MCID ) and the smallest detectable difference ( SDD ) and to examine their relation to required sample sizes for future studies using concrete data of the condition-specific Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and the generic Medical Outcomes Study 36-Item Short Form ( SF-36 ) in patients with osteoarthritis of the lower extremities undergoing a comprehensive inpatient rehabilitation intervention . METHODS SDD and MCID were determined in a prospect i ve study of 122 patients before a comprehensive inpatient rehabilitation intervention and at the 3-month followup . MCID was assessed by the transition method . Required SDD and sample sizes were determined by applying normal approximation and taking into account the calculation of power . RESULTS In the WOMAC sections the SDD and MCID ranged from 0.51 to 1.33 points ( scale 0 to 10 ) , and in the SF-36 sections the SDD and MCID ranged from 2.0 to 7.8 points ( scale 0 to 100 ) . Both question naires showed 2 moderately responsive sections that led to required sample sizes of 40 to 325 per treatment arm for a clinical study with unpaired data or total for paired followup data . CONCLUSION In rehabilitation intervention , effects larger than 12 % of baseline score ( 6 % of maximal score ) can be attained and detected as MCID by the transition method in both the WOMAC and the SF-36 . Effects of this size lead to reasonable sample sizes for future studies lying below n = 300 . The same holds true for moderately responsive question naire sections with effect sizes higher than 0.25 . When design ing studies , assumed effects below the MCID may be detectable but are clinical ly meaningless

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Quality of life changes in COPD patients treated with salmeterol.

Changes in health-related quality of life ( HRQoL ) were evaluated in patients with chronic obstructive pulmonary disease ( COPD ) following treatment with placebo , salmeterol 50 microg twice a day or 100 microg twice a day by metered-dose inhaler . Patients completed the disease-specific St. George 's Respiratory Question naire ( SGRQ ) and the Medical Outcomes Study Short Form 36 ( SF-36 ) at baseline and after 16 wk of treatment . Data from 283 patients ( 95 patients in the placebo group and 94 in each salmeterol group ) were available for HRQoL analysis . Apart from a small difference in ages , all treatment groups were well matched at baseline in terms of forced expiratory volume in one second ( FEV1 ) and HRQoL scores . Compared with placebo , salmeterol 50 microg twice a day was associated with significant improvements in SGRQ " Total " and " Impacts " scores which exceeded the threshold for a clinical ly significant change . This was not seen with salmeterol 100 microg twice a day . Changes in SGRQ and SF-36 scores correlated . They also showed a weak but significant relationship with FEV1 . This study has shown that a modest change in lung function may be associated with clinical ly significant gain in health and well-being in COPD patients

There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options . Negative changes were not associated with larger ESs . Population -based estimation procedures and brief follow-up were associated with smaller ESs , and acute conditions with larger ESs .

Background . A number of studies have computed the minimally important difference ( MID ) for health-related quality of life instruments . To determine whether there is consistency in the magnitude of MID estimates from different instruments .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

A Randomized, Naturalistic, Parallel-Group Study for the Long-Term Treatment of Panic Disorder With Clonazepam or Paroxetine

Abstract This long-term extension of an 8-week r and omized , naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam ( n = 47 ) and paroxetine ( n = 37 ) over a 3-year total treatment duration . Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine ( both taken at bedtime ) . This study reports data from the long-term period ( 34 months ) , following the initial 8-week treatment phase . Thus , total treatment duration was 36 months . Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine , but patients with partial primary treatment success were switched to the combination therapy . At initiation of the long-term study , the mean doses of clonazepam and paroxetine were 1.9 ( SD , 0.30 ) and 38.4 ( SD , 3.74 ) mg/d , respectively . These doses were maintained until month 36 ( clonazepam 1.9 [ SD , 0.29 ] mg/d and paroxetine 38.2 [ SD , 3.87 ] mg/d ) . Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)–Improvement rating than treatment with paroxetine ( mean difference : CGI-Severity scale −3.48 vs −3.24 , respectively , P = 0.02 ; CGI-Improvement scale 1.06 vs 1.11 , respectively , P = 0.04 ) . Both treatments similarly reduced the number of panic attacks and severity of anxiety . Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine ( 28.9 % vs 70.6 % , P < 0.001 ) . The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course . There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Modeling the longitudinal latent effect of pregabalin on self-reported changes in sleep disturbances in outpatients with generalized anxiety disorder managed in routine clinical practice

Background Anxiety disorders are among the most common psychiatric illnesses , with generalized anxiety disorder ( GAD ) being one of the most common . Sleep disturbances are highly prevalent in GAD patients . While treatment with pregabalin has been found to be associated with significant improvement in GAD-related sleep disturbance across many controlled clinical trials , mediational analysis has suggested that a substantial portion of this effect could be the result of a direct effect of pregabalin . Thus , the objective of this study was to model the longitudinal latent effect of pregabalin or usual care ( UC ) therapies on changes in sleep in out patients with GAD under routine clinical practice . Methods Male and female GAD out patients , aged 18 years or above , from a 6-month prospect i ve noninterventional trial were analyzed . Direct and indirect effects of either pregabalin or UC changes in anxiety symptoms ( assessed with Hamilton Anxiety Scale ) and sleep disturbances ( assessed with Medical Outcomes Study -Sleep Scale [ MOS-S ] ) were estimated by a conditional latent curve model applying structural equation modeling . Results A total of 1,546 pregabalin-naïve patients were analyzed , 984 receiving pregabalin and 562 UC . Both symptoms of anxiety and sleep disturbances were significantly improved in both groups , with higher mean ( 95 % confidence interval ) score reductions in subjects receiving pregabalin : −15.9 ( −15.2 ; −16.6 ) vs −14.5 ( −13.5 ; −15.5 ) , P=0.027 , in Hamilton Anxiety Scale ; and −29.7 ( −28.1 ; −31.3 ) vs −24.0 ( −21.6 ; −26.4 ) , P<0.001 , in MOS-S. The conditional latent curve model showed that the pregabalin effect on sleep disturbances was significant ( γ = −3.99 , P<0.001 ) , after discounting the effect on reduction in anxiety symptoms . A mediation model showed that 70 % of the direct effect of pregabalin on sleep remained after discounting the mediated effect of anxiety improvement . Conclusion A substantial proportion of the incremental improvements in anxiety-related sleep disturbances with pregabalin vs UC were explained by its direct effect , not mediated by improvements in anxiety symptoms

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Remission of Generalized Anxiety Disorder after 6 Months of Open-Label Treatment with Venlafaxine XR

Background : Remission has become one of the leading outcome criteria in clinical trials . Data collected by this research group assessed the rate of remission after 6 months of treatment of generalized anxiety disorder ( GAD ) with venlafaxine XR , to search for predictors of remission and to define how early on in treatment later remission can be predicted . Method : Two hundred sixty-eight patients with a GAD diagnosis enrolled into an open-label 6-month-treatment trial with venlafaxine XR ( 75 - 225 mg/day ) . Remission was defined by a Hamilton anxiety scale total score ≤7 . Logistic regression approaches were used to find out how early on in treatment later remission could be predicted , as well as to determine predictors of remission . In addition , adverse events were also followed over time . Results : While the total enrolled patient sample ( n = 268 ) had a remission rate of 53 % , 6-month completers ( n = 159 ) had a remission rate of 79 % . The only statistically significant predictor of remission , independent of baseline anxiety and depression levels , was a low Eysenck neuroticism score . The remission status outcome could best be predicted after 8 weeks of treatment when a CGI-I score of 1 or 2 predicted later remission with 78 % accuracy and later nonremission with 91 % accuracy . The incidence of adverse events decreased over the 6-month period , with sexual adverse events decreasing the least . Conclusion : The only significant predictor of remission was a low score on the Eysenck neuroticism scale . The earliest reliable prediction of later remission , based on improvement , could be made after 8 weeks of treatment with 91 % accuracy

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Long-term evaluation of paroxetine, clomipramine and placebo in panic disorder. Collaborative Paroxetine Panic Study Investigators.

Paroxetine has been shown to be effective in panic disorder in three 10- to 12-week studies . This trial studied the longer term effects of paroxetine in patients with DSM-III-R defined panic disorder . Patients who satisfactorily completed a 12-week , double-blind , placebo-controlled study of paroxetine and clomipramine could choose to continue receiving their r and omized treatment for a further 36 weeks . Efficacy assessment s included the daily panic attack diary , the Clinical Global Impression Scale , the Hamilton Anxiety Rating Scale , the Marks Sheehan Phobia Scale and the Sheehan Disability Scale . In total , 176 patients were included in the intention-to-treat population . The number of full panic attacks decreased in all three groups during the 12-week study , and improvements continued with long-term therapy . Paroxetine was statistically significantly more effective than placebo throughout the long-term study with respect to reduction from baseline of full panic attacks , and at the end of treatment with respect to the proportion of patients who eventually experienced no panic attacks . There were no significant differences between paroxetine and clomipramine . The proportion of patients who withdrew from the study due to adverse effects was greater in the clomipramine group ( 19 % ) than in either the paroxetine group ( 7 % ) or the placebo group ( 9 % ) . Paroxetine was significantly more effective than placebo and as effective as ( but better tolerated than ) clomipramine in the long-term treatment of panic disorder . Not only was efficacy maintained , but continued improvement was also seen , indicating the importance of long-term treatment in patients with panic disorder

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Interaction between polymorphisms in serotonin transporter (SLC6A4) and serotonin receptor 2A (HTR2A) genes predict treatment response to venlafaxine XR in generalized anxiety disorder

Variation in genes involved in serotonergic signaling is thought to be associated with antidepressant treatment response in generalized anxiety disorder ( GAD ) . We examined a possible interaction between the serotonin transporter gene ( SLC6A4 ) 5-HTTLPR/rs25531 haplotype and the serotonin 2A receptor gene ( HTR2A ) single-nucleotide polymorphism ( SNP ) rs7997012 in antidepressant treatment outcome in GAD . Patients diagnosed with GAD received venlafaxine XR treatment as part of an 18-month relapse prevention study . Genotypes obtained for the 5-HTTLPR/rs25531 ( La/La , La/S or S/S ) haplotype and rs7997012 SNP ( G or A ) in the European American population ( n=112 ) were used for pharmacogenetic analysis . Our data show that subjects with genotypes La/La+G/G or La/La+G/A ( n=28 ) had significantly lower Hamilton Anxiety Scale ( HAM-A ) scores than those with genotypes La/S+A/A or S/S+A/A ( n=12 ) at 6 months ( HAM-A difference=10.7 ; P<0.0001 ) . Single-marker analysis only showed HAM-A differences of 4.3 ( 5-HTTLPR/rs25531 : La/La versus La/S+S/S ) and 4.8 ( rs7997012 : G/G+G/A versus A/A ) , showing for the first time a significant gene – gene interaction between these markers

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Extended release quetiapine fumarate (quetiapine XR) monotherapy as maintenance treatment for generalized anxiety disorder: a long-term, randomized, placebo-controlled trial

The objective of this study was to evaluate the efficacy and tolerability of extended release quetiapine fumarate ( quetiapine XR ) as maintenance monotherapy for patients with generalized anxiety disorder ( GAD ) . Time-to-event ( anxiety symptom recurrence ; maximum 52 weeks ) multicenter , r and omized-withdrawal , parallel-group , double-blind , placebo-controlled study of quetiapine XR ( 50–300 mg/day ) following open-label run-in ( 4–8 weeks ) and open-label stabilization ( ≥12 weeks ) . Primary variable : time from r and omization to anxiety event . Secondary variables included : Hamilton Anxiety Rating Scale ( HAM-A ) total , HAM-A psychic/somatic anxiety factors , Clinical Global Impression-Severity of Illness ( CGI-S ) , and Quality of Life , Enjoyment and Satisfaction Question naire ( Q-LES-Q ) scores ; adverse events ( AE ) reporting . Four hundred and thirty-two patients , stabilized on quetiapine XR , were r and omized to continue quetiapine XR ( N=216 ) or switch to placebo ( N=216 ) . Risk of anxiety symptom recurrence was significantly reduced by 81 % for quetiapine XR versus placebo : hazard ratio=0.19 ( 95 % confidence interval 0.12–0.31 ; P<0.001 ) . Fewer patients receiving quetiapine XR ( N=22 , 10.2 % ) than placebo ( N=84 , 38.9 % ) experienced anxiety symptom recurrence . Significant differences were observed between quetiapine XR and placebo in : HAM-A total , psychic/somatic , CGI-S ( all P<0.001 ) and Q-LES-Q ( P<0.05 ) scores . AEs ( > 10 % ) during open-label treatment were dry mouth , sedation , somnolence , dizziness , fatigue , and constipation . During r and omized treatment , the most common AEs for quetiapine XR were headache and nasopharyngitis . Quetiapine XR monotherapy reduced the risk of anxiety symptom recurrence in patients with GAD stabilized on quetiapine XR , with tolerability results consistent with the known profile of quetiapine

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Genetic polymorphisms in the PACAP and PAC1 receptor genes and treatment response to venlafaxine XR in generalized anxiety disorder

The pituitary adenylate cyclase-activating peptide ( PACAP ) and its receptor ( PAC1 ) are involved in stress response and anxiety . Genotypes for PACAP/PAC1 were examined for effects on treatment response to venlafaxine XR in generalized anxiety disorder . The Asp54Gly ( rs2856966 ) variant in the PACAP gene was associated with better treatment outcome

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

2nd year maintenance and discontinuation of imipramine in panic disorder with agoraphobia.

BACKGROUND The results from our 1 year placebo-controlled maintenance/discontinuation study in remitted panic disorder with agoraphobia patients confirmed the significant prophylactic effectiveness of imipramine maintenance treatment but suggested that this may be necessary in only 37 % of the patients who relapse following discontinuation of 6 months acute imipramine treatment . This paper presents pilot data from a second year extension of the above-mentioned study with the aim of exploring the putative protective effects of maintenance imipramine therapy beyond the 1st year . METHOD Eighteen patients from the 30 who survived , in stable remission , the first 12 months of the maintenance/discontinuation study gave written consent to participate in a double-blind 2nd year extension phase with the knowledge that those on placebo will continue on the same condition ( N = 7 , PBO-PBO ) and those on imipramine ( N = 11 ) will be rer and omized to 2nd year maintenance ( N = 4 , IMI-IMI ) or placebo substitution ( N = 7 , IMI-PBO ) . The procedures continued unchanged from that of the 1st year of the study and patients were followed with planned assessment s every 2 months over the second 12-month experimental period of the study . RESULTS None of the IMI-IMI patients relapsed , two ( 28.5 % ) of the IMI-PBO patients relapsed , and two ( 28.5 % ) of PBO-PBO patients relapsed . The mean estimated time without relapse was 10 months and 9 months for IMI-PBO and PBO-PBO , respectively . The estimated probability of not relapsing was .64 for IMI-PBO and .60 for PBO-PBO ( Mantel-cox test chi2 = .84 , p = .77 ) . CONCLUSION These interlocking controlled observations tentatively suggest that a substantial degree of prophylactic efficacy continues and that a substantial need for continued prophylaxis exists beyond the 1st year of maintenance imipramine treatment in panic disorder with agoraphobia patients

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Rate of improvement during and across three treatments for panic disorder with or without agoraphobia: cognitive behavioral therapy, selective serotonin reuptake inhibitor or both combined.

BACKGROUND Existing literature on panic disorder ( PD ) yields no data regarding the differential rates of improvement during Cognitive Behavioral Therapy ( CBT ) , Selective Serotonin Reuptake Inhibitor ( SSRI ) or both combined ( CBT+SSRI ) . METHOD Patients were r and omized to CBT , SSRI or CBT+SSRI which each lasted one year including three months of medication taper . Participating patients kept record of the frequency of panic attacks throughout the full year of treatment . Rate of improvement on panic frequency and the relationship between rate of improvement and baseline agoraphobia ( AG ) were examined . RESULTS A significant decline in frequency of panic attacks was observed for each treatment modality . SSRI and CBT+SSRI were associated with a significant faster rate of improvement as compared to CBT . Gains were maintained after tapering medication . For patients with moderate or severe AG , CBT+SSRI was associated with a more rapid improvement on panic frequency as compared to patients receiving either mono-treatment . LIMITATIONS Frequency of panic attacks was not assessed beyond the full year of treatment . Second , only one process variable was used . CONCLUSIONS Patients with PD respond well to each treatment as indicated by a significant decline in panic attacks . CBT is associated with a slower rate of improvement as compared to SSRI and CBT+SSRI . Discontinuation of SSRI treatment does not result in a revival of frequency of panic attacks . Our data suggest that for patients without or with only mild AG , SSRI-only will suffice . For patients with moderate or severe AG , the combined CBT+SSRI treatment is recommended

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Maintenance drug treatment of panic disorder. I. Results of a prospective, placebo-controlled comparison of alprazolam and imipramine.

One hundred six patients diagnosed according to DSM-III as suffering from agoraphobia with panic disorder , panic disorder with limited phobic avoidance , or uncomplicated panic disorder entered an acute 8-week treatment phase . Patients who improved received an additional 6 months ' maintenance treatment . Significantly more patients treated with alprazolam than with imipramine hydrochloride or placebo remained in therapy and experienced panic attack and phobia relief during the acute treatment phase . During the maintenance phase , neither tolerance nor daily dose increase was observed . All patients who completed the maintenance phase ( 27 in the alprazolam group , 11 in the imipramine group , and 10 in the placebo group ) were panic free at the end of 8 months of study treatment . Alprazolam therapy was effective and well tolerated at a mean daily dose of 5.7 mg . Imipramine hydrochloride ( 175 mg/d ) also produced significant panic relief but was associated with poor patient acceptance

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Treatment-related alteration of cortisol predicts change in neuropsychological function during acute treatment of late-life anxiety disorder.

OBJECTIVE Older adults with anxiety disorders are burdened by impairment in neurocognition , which may be mediated by elevated circulating cortisol levels . In a r and omized controlled trial of acute serotonin-reuptake inhibitor treatment for late-life anxiety disorder , we examined whether change in salivary cortisol concentrations during treatment predicted improvements in measures of memory and executive function . METHODS We examined 60 adults aged 60 years and older , who took part in a 12-week trial of escitalopram versus placebo for generalized anxiety disorder . All subjects had pre-treatment and post-treatment assessment s that included monitoring of peak and total daily cortisol and a comprehensive neuropsychological evaluation . RESULTS Salivary cortisol changes during treatment showed significant associations with changes in immediate and delayed memory but no association with executive tasks ( measures of working memory and set shifting ) . Analyses suggested that a decrease in cortisol due to serotonin-reuptake inhibitor treatment was responsible for the memory changes : memory improvement was seen with cortisol reduction among patients receiving escitalopram but not among patients receiving placebo . CONCLUSION Serotonin-reuptake inhibitor-induced alteration in circulating cortisol during treatment of generalized anxiety disorder predicted changes in immediate and delayed memory . This finding suggests a novel treatment strategy in late-life anxiety disorders : targeting hypothalamic-pituitary- adrenal axis dysfunction to improve memory

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Pregabalin long-term treatment and assessment of discontinuation in patients with generalized anxiety disorder.

Discontinuation effects following cessation of 12 and 24 wk of pregabalin treatment for generalized anxiety disorder ( GAD ) were evaluated in a placebo- and lorazepam-controlled , r and omized , double-blind , multicentre trial conducted in 16 countries . The study design consisted of two 12-wk treatment periods ( periods 1 and 2 ) , each followed by a 1-wk taper and two post-discontinuation assessment s , one immediately following the taper and one 1-wk post-taper . Patients were assigned to receive an initially flexible dose of pregabalin 450 - 600 mg/d , pregabalin 150 - 300 mg/d , or lorazepam 3 - 4 mg/d for 6 wk ; responders continued fixed-dose therapy for 6 additional weeks . Patients entering period 2 continued on the same fixed dose or switched to placebo . Discontinuation effects were evaluated with the Physician Withdrawal Checklist ( PWC ) and reported discontinuation-emergent signs and symptoms . Rebound anxiety was measured with the Hamilton Anxiety Rating Scale . GAD symptoms improved with all treatments and improvements were maintained over 12 and 24 wk . Low levels of discontinuation symptoms were evident in all treatment groups . For patients who received active treatment during both periods , mean ( 95 % confidence interval ) increases on the PWC from last visit on active treatment to the second post-discontinuation assessment were : pregabalin 450 - 600 mg/d : 2.8 ( 1.6 - 3.9 ) , pregabalin 150 - 300 mg/d : 1.7 ( 0.7 - 2.8 ) , lorazepam 3 - 4 mg/d : 2.2 ( 1.0 - 3.5 ) . Rates of rebound anxiety were also low at both 12 and 24 wk ( 0 - 6 % ) . This suggests that risk of discontinuation symptoms and rebound anxiety are low for pregabalin after 12 and 24 wk of treatment

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Broadening of Generalized Anxiety Disorders Definition Does not Affect the Response to Psychiatric Care: Findings from the Observational ADAN Study

Objective : To eluci date the consequences of broadening DSM-IV criteria for generalized anxiety disorder ( GAD ) , we examined prospect ively the evolution of GAD symptoms in two groups of patients ; one group diagnosed according to DSM-IV criteria and the other , according to broader criteria . Method : Multicentre , prospect i ve and observational study conducted on outpatient psychiatric clinics . Patients were selected from October 2007 to January 2009 and diagnosed with GAD according to DSM-IV criteria ( DSM-IV group ) or broader criteria . Broader criteria were considered 1-month of excessive or non-excessive worry and only 2 of the associated symptoms listed on DSM-IV for GAD diagnosis . Socio-demographic data , medical history and functional outcome measures were collected three times during a 6-month period . Results : 3,549 patients were systematic ally recruited ; 1,815 patients in DSM-IV group ( DG ) and 1,264 in broad group ( BG ) ; 453 patients did not fulfil inclusion criteria and were excluded . Most patients ( 87.9 % in DG , 82.0 % in BG ) were currently following pharmacological therapies ( mainly benzodiazepines ) to manage their anxiety symptoms . The changes observed during the study were : 49.0 % and 58.0 % , respectively of patients without anxiety symptoms as per HAM-A scale at the 6 month visit ( p=0.261 ) and 59.7 % and 67.7 % , respectively ( p=0.103 ) of responder rates ( > 50 % reduction of baseline scoring ) . Conclusion : Broadening of GAD criteria does not seem to affect psychiatric care results in subjects with GAD , is able to identify the core symptoms of the disease according to the DSM-IV criteria and could lead to an earlier diagnosis

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Three year naturalistic outcome study of panic disorder patients treated with paroxetine

Background This naturalistic open label follow-up study had three objectives :1 ) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment2 ) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia.3 ) To observe paroxetine 's tolerability over a 24 month period . Methods 143 patients with panic disorder ( PD ) , with or without agoraphobia , successfully finished a short-term ( ie 12 week ) trial of paroxetine treatment . All patients then continued to receive paroxetine maintenance therapy for a total of 12 months . At the end of this period , 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase . The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored , as in the first group , for another year while medication-free . The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a r and omized manner . Results Only 21 of 143 patients ( 14 % ) relapsed during the one year medication discontinuation follow-up phase . There were no significant differences in relapse rates between the patients who received intermediate-term ( up to 12 months ) paroxetine and those who chose the long-term course ( 24 month paroxetine treatment ) . 43 patients ( 30.1 % ) reported sexual dysfunction . The patients exhibited an average weight gain of 5.06 kg . All patients who eventually relapsed demonstrated significantly greater weight increase ( 7.3 kg ) during the treatment phase . Conclusions The extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation . Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Time to relapse after 6 and 12 months' treatment of generalized anxiety disorder with venlafaxine extended release.

CONTEXT Generalized anxiety disorder ( GAD ) is a chronic disorder in need of reliable data to guide long-term treatment . OBJECTIVES To assess the benefits of 6 and 12 months ' treatment of GAD with venlafaxine hydrochloride extended release ( XR ) in patients who improved after 6 months ' open-label venlafaxine XR treatment . DESIGN After 6 months ' open-label venlafaxine XR treatment , improved patients were r and omized to venlafaxine XR or placebo for 6 months . All venlafaxine XR patients still in the study at 12 months were r and omized to receive venlafaxine XR or placebo , and all placebo patients continued taking placebo for another 6 months . SETTING One urban site ( 5 locations ) . PATIENTS Of 268 patients with a diagnosis of GAD entering the open-label venlafaxine XR treatment phase , 158 ( 59.0 % ) completed 6 months , and 136 ( 50.7 % ) entered relapse phase 2 ( 6 - 12 months ) . Fifty-nine ( 43.4 % ) of 136 patients entered phase 3 ( 12 - 18 months ) . INTERVENTION Six months ' open-label treatment with venlafaxine XR , followed by double-blind venlafaxine XR or placebo for 2 relapse phases , each lasting 6 months . MAIN OUTCOME MEASURES Time to relapse while receiving venlafaxine XR or placebo after 6 and after 12 months of treatment . Relapse was strictly defined to safeguard against assigning patients with venlafaxine XR discontinuation symptoms or temporary anxiety increase as relapse . RESULTS For objective 1 , relapse rates in phase 2 ( months 6 - 12 ) were 9.8 % on venlafaxine XR and 53.7 % on placebo ( P < .001 ) . For objective 2 , relapse rates after 12 months on placebo ( 32.4 % ) were lower than after 6 months on venlafaxine XR ( 53.7 % ) ( P < .03 ) . CONCLUSIONS Treatment of GAD with an antidepressant should be continued for at least 12 months . Preliminary data demonstrate that improved patients who relapse while off their antianxiety medication after at least 6 months of treatment will again most likely respond to a second course of treatment with the same medication . Trial Registration clinical trials.gov Identifier : NCT00183274

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Effects of once-daily extended release quetiapine fumarate on patient-reported outcomes in patients with generalized anxiety disorder

Background We evaluated the effects of once-daily extended-release quetiapine fumarate ( quetiapine XR ) on patient-reported outcomes in generalized anxiety disorder ( GAD ) . Methods This is a report of a pooled analysis from three acute 8-week , r and omized , placebocontrolled , fixed-dose ( 50 , 150 , 300 mg/day ) studies and a 52-week maintenance flexible dose ( 50–300 mg/day ) study of quetiapine XR monotherapy in patients with GAD . Quality of Life Enjoyment and Satisfaction Question naire Short Form ( Q-LES-Q-SF ) percent maximum total scores ( items 1–14 ) , item 15 ( “ satisfaction with medication ” ) , item 16 ( “ overall life satisfaction ” ) , and Pittsburgh Sleep Quality Index ( PSQI ) global scores are reported . Sheehan Disability Scale ( SDS ) total scores were also assessed ( maintenance study only ) . Results The acute studies showed significant improvements at week 8 in Q-LES-Q-SF percent maximum total score with quetiapine XR 150 mg/day ( P < 0.001 ) and item 16 with quetiapine XR 50 ( P < 0.05 ) and 150 mg/day ( P < 0.001 ) versus placebo ; PSQI global scores significantly improved with quetiapine XR 50 , 150 , and 300 mg/day versus placebo ( P < 0.001 ) . The maintenance study showed significant benefits versus placebo with quetiapine XR 50–300 mg/day in Q-LES-Q-SF percent total score , item 15 and item 16 scores , PSQI global score , and SDS total score . Conclusion Quetiapine XR 150 mg/day ( acute studies ) and 50–300 mg/day ( maintenance study ) improved quality of life , overall functioning , and sleep quality in patients with GAD

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Personality disorders and time to remission in generalized anxiety disorder, social phobia, and panic disorder.

BACKGROUND This investigation assessed the effect of personality disorders ( PersDs ) on time to remission in patients with generalized anxiety disorder , social phobia , or panic disorder . METHODS Selected Axis I and II predictors of time to remission during 5 years of follow-up were assessed in 514 patients with 1 or more of these anxiety disorders who participated in the Harvard/Brown Anxiety Research Program , a multisite , prospect i ve , longitudinal , naturalistic study . RESULTS The presence of a PersD predicted a 30 % lower likelihood of generalized anxiety disorder remission , a 39 % lower likelihood of social phobia remission , and no difference in likelihood of panic disorder remission . More specifically , a lower likelihood of remission from generalized anxiety disorder was predicted by the presence of avoidant PersD ( 34 % lower ) and dependent PersD ( 14 % lower ) . The presence of avoidant PersD predicted a 41 % lower likelihood of social phobia remission . The presence of major depressive disorder did not account for these findings . CONCLUSIONS Our findings provide new data on the pernicious effect of PersDs on the course of generalized anxiety disorder and social phobia but not panic disorder , suggesting that PersDs have a differential effect on the outcome of anxiety disorders

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

The Nottingham Study of Neurotic Disorder: predictors of 12-year outcome of dysthymic, panic and generalized anxiety disorder.

BACKGROUND Controlled prospect i ve studies of the simultaneous long-term outcome of several mental disorders are rare . This study sought to determine if there were important differences between the outcome of anxiety and depressive disorders after 12 years and to examine their main predictors . METHOD A cohort of 210 people seen in general practice psychiatric clinics with a DSM-III diagnosis of generalized anxiety disorder ( 71 ) , panic disorder ( 74 ) , or dysthymic disorder ( 65 ) , including combined anxiety-depressive disorder ( cothymia ) ( 67 ) was followed up after 12 years . Interview assessment s of symptoms , social functioning and outcome were made , the latter using a new scale , the Neurotic Disorder Outcome Scale . Seventeen baseline predictors were also examined . RESULTS Data were obtained from 201 ( 96 % ) patients , 17 of whom had died . Only 73 ( 36 % ) had no DSM diagnosis at the time of follow-up . Using univariate and stepwise multiple linear regression those with cothymia , personality disorder , recurrent episodes and greater baseline self-rated anxiety and depression ratings had a worse outcome than others ; initial diagnosis did not contribute significantly to outcome and instability of diagnosis over time was much more common than consistency . CONCLUSION Only two out of five people with the common neurotic disorders have a good outcome despite alleged advances in treatment . Those with greater mood symptoms and pre-morbid personality disorder have the least favourable outcome . It is suggested that greater attention be paid to the concurrent treatment of personality disorder and environmental factors rather than symptoms as these may be the real cause of apparent treatment resistance

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Antipanic Drug Modulation Of 35% CO2 Hyperreactivity and Short-Term Treatment Outcome

Carbon dioxide ( CO2 ) inhalation induces acute anxiety and panic attacks in patients with Panic Disorder ( PD ) . Anti-panic drugs decrease CO2 reactivity after the first days of treatment ; however , the clinical meaning of this finding has not yet been established . This study investigated the effects of treatment with tricyclic antidepressants and selective serotonin re-uptake inhibitors ( SSRIs ) on CO2 reactivity and compared the relationships between 35 % CO2 hyperreactivity modulation and short-term clinical outcome . One hundred twenty-three patients with PD with or without agoraphobia who were hyperreactive to CO2 were r and omly assigned to treatment groups with imipramine , clomipramine , paroxetine , sertraline , or fluvoxamine . A double-blind , r and omized design was applied . Each patient received the 35 % CO2 challenge on days 0 , 7 , and 30 . The severity of clinical symptomatology was measured on days 0 and 30 . Decreased hyperreactivity to 35 % CO2 in all five treatment groups was already evident after the first week . The decrease in CO2 reactivity at the end of treatment was proportional to the degree of clinical improvement . Multiple regression analyses showed that the decrease in CO2 reactivity after the first week was a significant predictor for good clinical outcome after one month . The results of this study confirm evidence that psychoactive drugs effective in the treatment of PD decrease CO2 hyperreactivity . They also suggest that precocious modulation of CO2 reactivity might fairly reliably predict short-term clinical outcome in patients with “ respiratory ” PD

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

The diagnosis and treatment of generalized anxiety disorder.

BACKGROUND Generalized anxiety disorder ( GAD ) is a common and serious disease with a lifetime prevalence of 4.3 % to 5.9 % . It is underdiagnosed in primary care . METHODS Recommendations on the treatment of GAD are given on the basis of all available findings from pertinent r and omized trials , retrieved by a selective search of the literature . RESULTS Among psychotherapeutic techniques , various kinds of cognitive behavioral therapy ( CBT ) have been found useful in controlled trials . The drugs of first choice include selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-norepinephine reuptake inhibitors ( SNRIs ) , and the calcium-channel modulator pregabalin . Tricyclic antidepressants are also effective but have more adverse effects than SSRIs . Although benzodiazepines are effective anxiolytic agents for short-term use , they should not be given over the long term because of the danger of addiction . Buspirone , an azapirone , was found to be effective in a small number of trials , but the findings across trials are inconsistent . The response rate of GAD to CBT in published studies lies between 47 % and 75 % , while its response rate to drug treatment lies between 44 % and 81 % . CONCLUSION The treatment of GAD with CBT and drugs is evidence -based and has a good chance of improving the manifestations of the disorder

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Agomelatine prevents relapse in generalized anxiety disorder: a 6-month randomized, double-blind, placebo-controlled discontinuation study.

OBJECTIVE This study evaluated the efficacy and tolerability of agomelatine in the prevention of relapse in patients with generalized anxiety disorder ( GAD ) . METHOD Patients with GAD ( Hamilton Anxiety Rating Scale [ HARS ] ≥ 22 , with items 1 and 2 ≥ 2 , item 1 + 2 ≥ 5 ; Montgomery-Asberg Depression Rating Scale [ MADRS ] ≤ 16 ; and < 20 % decrease in HARS total score between screening and baseline ) who responded to a 16-week course of agomelatine 25 - 50 mg/d treatment were r and omly assigned to receive continuation treatment with agomelatine ( n = 113 ) or placebo ( n = 114 ) for 26 weeks . The main outcome measure was time to relapse during this maintenance period . The estimated risk of relapse was calculated using the Kaplan-Meier method , and groups were compared using a log-rank test stratified for country . The study was undertaken in 31 clinical centers in Canada , Denmark , Estonia , Finl and , Hungary , and Sweden from November 2007 to September 2009 . RESULTS During the 6-month maintenance period , the proportion of patients that relapsed during the double-blind period in the agomelatine group ( 22 patients , 19.5 % ) was lower than in the placebo group ( 35 patients , 30.7 % ) . The risk of relapse over time was significantly lower for patients who continued treatment than for those switched to placebo ( P = .046 , log-rank test stratified for country ) . Agomelatine was also superior to placebo in preventing relapse in the subset of more severe patients with baseline HARS total score ≥ 25 and CGI-S score ≥ 5 . The tolerability of agomelatine was good throughout the study , and there were no differences in discontinuation symptoms after withdrawal of agomelatine in comparison to maintenance on agomelatine . CONCLUSIONS The present study extends the positive findings of an earlier short-term study of agomelatine in GAD , demonstrating that agomelatine is effective and well-tolerated in the longer-term treatment of this chronic disorder . TRIAL REGISTRATION www.is rct n.org identifier : IS RCT N38094599

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study.

OBJECTIVE The authors sought to observe the long-term clinical course of anxiety disorders over 12 years and to examine the influence of comorbid psychiatric disorders on recovery from or recurrence of panic disorder , generalized anxiety disorder , and social phobia . METHOD Data were drawn from the Harvard/Brown Anxiety Disorders Research Program , a prospect i ve , naturalistic , longitudinal , multicenter study of adults with a current or past history of anxiety disorders . Probabilities of recovery and recurrence were calculated by using st and ard survival analysis methods . Proportional hazards regression analyses with time-varying covariates were conducted to determine risk ratios for possible comorbid psychiatric predictors of recovery and recurrence . RESULTS Survival analyses revealed an overall chronic course for the majority of the anxiety disorders . Social phobia had the smallest probability of recovery after 12 years of follow-up . Moreover , patients who had prospect ively observed recovery from their intake anxiety disorder had a high probability of recurrence over the follow-up period . The overall clinical course was worsened by several comorbid psychiatric conditions , including major depression and alcohol and other substance use disorders , and by comorbidity of generalized anxiety disorder and panic disorder with agoraphobia . CONCLUSIONS These data depict the anxiety disorders as insidious , with a chronic clinical course , low rates of recovery , and relatively high probabilities of recurrence . The presence of particular comorbid psychiatric disorders significantly lowered the likelihood of recovery from anxiety disorders and increased the likelihood of their recurrence . The findings add to the underst and ing of the nosology and treatment of these disorders

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Switching from long-term benzodiazepine therapy to pregabalin in patients with generalized anxiety disorder: a double-blind, placebo-controlled trial

To evaluate the efficacy of pregabalin in facilitating taper off chronic benzodiazepines , out patients ( N = 106 ) with a lifetime diagnosis of generalized anxiety disorder ( current diagnosis could be subthreshold ) who had been treated with a benzodiazepine for 8–52 weeks were stabilized for 2–4 weeks on alprazolam in the range of 1–4 mg/day . Patients were then r and omized to 12 weeks of double-blind treatment with either pregabalin 300–600 mg/day or placebo while undergoing a gradual benzodiazepine taper at a rate of 25 % per week , followed by a 6-week benzodiazepine-free phase during which they continued double-blind study treatment . Outcome measures included ability to remain benzodiazepine-free ( primary ) as well as changes in Hamilton Anxiety Rating Scale (HAM)-A and Physician Withdrawal Checklist ( PWC ) . At endpoint , a non-significant higher proportion of patients remained benzodiazepine-free receiving pregabalin compared with placebo ( 51.4 % vs 37.0 % ) . Treatment with pregabalin was associated with significantly greater endpoint reduction in the HAM-A total score versus placebo ( −2.5 vs + 1.3 ; p < 0.001 ) , and lower endpoint mean PWC scores ( 6.5 vs 10.3 ; p = 0.012 ) . Thirty patients ( 53 % ) in the pregabalin group and 19 patients ( 37 % ) in the placebo group completed the study , reducing the power to detect a significant difference on the primary outcome . The results on the anxiety and withdrawal severity measures suggest that switching to pregabalin may be a safe and effective method for discontinuing long-term benzodiazepine therapy

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Long-term efficacy of pregabalin in generalized anxiety disorder

A multicenter , r and omized , placebo-controlled , double-blind study was conducted to evaluate the efficacy of pregabalin in preventing relapse of generalized anxiety disorder ( GAD ) after response to short-term treatment . Out patients ( n=624 ) with GAD for ≥1 year received open-label pregabalin ( 450 mg/day ) for 8 weeks and , if a clinical response was observed , were r and omized to receive either pregabalin ( 450 mg/day ; n=168 ) or placebo ( n=170 ) for 24 weeks . The primary efficacy parameter was time to relapse . Among responders to open-label acute treatment with pregabalin , time to relapse of GAD was significantly longer for patients treated with pregabalin compared with placebo ( P<0.0001 ) . Fifty per cent of the placebo group had relapsed by day 23 , and at study endpoint , 65 % had relapsed . In the pregabalin group , only 42 % had relapsed by study end . Total attrition during double-blind treatment was somewhat higher on pregabalin compared with placebo ( 21.4 vs. 15.3 % ) ; attrition owing to adverse events ( AEs ) was also somewhat higher on pregabalin ( 6.0 vs. 2.4 % ) . AEs were relatively low in the double-blind phase ; only three AEs occurred with an incidence of more than 5 % on pregabalin and placebo , respectively : infection ( 14.9 vs. 11.2 % ) , headache ( 10.1 vs. 11.2 % ) , and somnolence ( 6.0 vs. 0 % ) . No safety concerns were identified with long-term treatment . The study indicates that pregabalin is an effective treatment for the prevention of relapse in patients with GAD

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Predictors of outcome of pharmacological and psychological treatment of late-life panic disorder with agoraphobia.

OBJECTIVE This study aims to evaluate the differential predictive values of age , age of onset and duration of illness on paroxetine and cognitive-behavioural therapy ( CBT ) outcome in late-life panic disorder with agoraphobia . METHOD Patients 60 years and older with a confirmed diagnosis of panic disorder with agoraphobia ( n = 49 ) were r and omly assigned to paroxetine ( 40 mg/day ) treatment , individual CBT or a waiting-list control condition . Multiple regression analyses were conducted per treatment arm with post-treatment avoidance behaviour and agoraphobic cognitions as the dependent variables . RESULTS Higher age at onset and shorter duration of illness were predictors of superior outcomes following CBT , although these variables did not influence the treatment effects of paroxetine . CONCLUSIONS In late-life agoraphobic panic disorder , chronological age has no impact on treatment modality outcome . In older patients with a late disease onset or shorter duration of illness , CBT is to be preferred over paroxetine , whereas paroxetine might be the treatment of choice for older people with an early onset and short duration of illness

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Duration of Imipramine Therapy and Relapse in Panic Disorder With Agoraphobia

It has been suggested that maintenance treatment of patients who have remitted panic disorder with agoraphobia beyond the six months of acute phase imipramine treatment may decrease the risk of relapse . This study further explores the relationship between relapse and duration of imipramine treatment in this population . Fifty-one patients , all in remission at the end of six months acute phase open trial with imipramine 2.25 mg/kg/day and r and omized to double-blind maintenance or placebo substitution , discontinued imipramine treatment eventually and were followed over a 12-month risk period : 27 during first year placebo substitution , 7 after 12 months of imipramine maintenance in placebo substitution , and 17 after variable duration s of imipramine maintenance in open discontinuation . There were no behaviorally oriented interventions or instructions at any time during the acute and maintenance phases of treatment or during imipramine discontinuation . Duration of imipramine treatment , the method of discontinuation ( open versus placebo substitution ) , or any of the 9 variables from the demographic , clinical , and open treatment domains that were entered in a Cox proportional hazard model did not predict relapse . The rate of relapse after only 6 months of treatment ( 10 out of 27 , 37 % ) was identical to the rate of relapse after 12 to 30 months of treatment ( 9 out of 24 , 37.5 % ) . The results suggest a lack of specific protective effects beyond prophylaxis and underscore the difficulty in predicting relapse in fully remitted panic disorder with agoraphobia patients . Early detection of relapse in patients who discontinue treatment may be a viable alternative to prediction

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

A 15-year follow-up study of patients with panic disorder.

BACKGROUND Panic disorder ( PD ) is generally regarded as a chronic condition with considerable variation in severity of symptoms . AIMS To describe the long-term outcome of naturalistically treated PD . METHODS Fifty-five out patients with PD , who participated in a placebo-controlled drug trial of the efficacy of alprazolam and imipramine 15 years ago were reassessed with the same instruments used in the original study . RESULTS Complete recovery ( no panic attacks and no longer on medication during the last 10 years ) was seen in 18 % of patients , and an additional 13 % recovered but were still on medication . Fifty-one percent experienced recurrent anxiety attacks whereas 18 % still met diagnostic criteria for PD . The incidence of agoraphobia decreased from 69 % to 20 % . Patients with agoraphobia at admission tended to have a poorer long-term outcome according to daily functioning compared with patients without agoraphobia at admission , although both groups reported improved daily functioning at follow-up . Maintenance medication was common . No benzodiazepine abuse was reported . CONCLUSION PD has a favourable outcome in a substantial proportion of patients . However , the illness is chronic and needs treatment . The short-term treatment given in the drug trial had no influence on the long-term outcome

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Relation of Serotonin Transporter Genetic Variation to Efficacy of Escitalopram for Generalized Anxiety Disorder in Older Adults

Objective : Generalized anxiety disorder ( GAD ) is common in older adults and can be treated with selective serotonin reuptake inhibitors ( SSRIs ) . Genetic variation in the serotonin transporter gene promoter region is posited to be associated with SSRI efficacy : 2 polymorphisms ( 5-HTTLPR S/L and rs25531 g/a ) form a haplotype with the La combination having higher transcription activity than other haplotypes . We hypothesized that GAD patients with no La haplotypes ( La− ) have lower SSRI treatment efficacy than those with 1 to 2 La haplotypes ( La+ ) . Method : The study enrolled subjects aged 60 years or older with a principal diagnosis of GAD into a 12-week , r and omized trial of escitalopram versus placebo . One hundred fifty subjects were genotyped for the serotonin transporter promoter region haplotype and were divided into La− and La+ genotype groups ; the primary analyses were done in European Americans only ( n = 125 ; n = 59 with escitalopram and n = 66 with placebo ) . Results : Escitalopram had no efficacy in the La− group versus moderate efficacy in the La+ group . This genetic moderation of SSRI efficacy was due to a higher placebo response in La− subjects , compared with La+ subjects . Drug concentration did not affect the genetic results . Exploratory analyses suggest that La− subjects had greater variability of anxiety symptoms unrelated to treatment . Conclusions : The serotonin transporter promoter haplotype is associated with variability in SSRI efficacy for late-life GAD . The variability may result from a genetic effect on anxiety symptom variability unrelated to treatment , rather than a pharmacodynamic effect that has been previously assumed . Further research is needed to underst and the pharmacogenetic mechanism of this haplotype

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Variation in the catechol-O-methyltransferase (COMT) gene and treatment response to venlafaxine XR in generalized anxiety disorder

Antidepressant drugs are the preferred choice for the treatment of generalized anxiety disorder ( GAD ) . However , the choice of pharmacotherapy is determined on a trial- and -error basis , as the underlying mechanisms of treatment response are unknown . We examined whether the COMT gene , which has been known to play a role in antidepressant treatment response in major depressive disorder ( MDD ) , has a pharmacogenetic effect in antidepressant treatment response in GAD . In our study , 156 patients diagnosed with GAD received venlafaxine XR treatment as part of an 18-month relapse prevention study . Genotypes were obtained for the COMT functional variant rs4680 ( Val158Met ) for all patients ; however , pharmacogenetic analysis was only conducted for the European American population ( n=112 ) . We found no significant association between our primary Hamilton Anxiety Scale outcome measure and rs4680 . However , we did find a nominally significant allelic association between this variant and a secondary treatment outcome measure ( CGI-I ) in our European American population ( n=112 ) . Furthermore , we show a slight dominant effect of the A-allele with the CGI-I measure in the European American population indicating a possible pharmacogenetic role of rs4680 in antidepressant treatment outcome in GAD . Further studies in a larger population are needed to confirm this effect

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

A randomized controlled study of paroxetine and cognitive‐behavioural therapy for late‐life panic disorder

Hendriks G‐J , Keijsers GPJ , Kampman M , Oude Voshaar RC , Verbraak MJPM , Broekman TG , Hoogduin CAL . A r and omized controlled study of paroxetine and cognitive‐behavioural therapy for late‐life panic disorder

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Long-term treatment of anxiety disorders with pregabalin: a 1 year open-label study of safety and tolerability

Abstract Objective : Short-term clinical trials have demonstrated the efficacy and safety of pregabalin in the treatment of generalized anxiety disorder ( GAD ) . This study examined long-term safety and tolerability of pregabalin in patients with GAD , social anxiety disorder ( SAD ) , or panic disorder ( PD ) . Research design and methods : Patients ( n = 528 ) completing one of four r and omized , double-blind , placebo-controlled trials of pregabalin for GAD , SAD , or PD were treated , open label , with flexible-dose pregabalin ( 150–600 mg/day ) for 1 year . Clinical trial registration : NCT00150449 . Main outcome measures : The primary outcomes were safety and tolerability . Illness severity was assessed at baseline and Weeks 27/52 using the Clinical Global Impression of Severity ( CGI-S ) scale . Patients were characterized as ‘ responders ’ or ‘ non-responders ’ based on CGI-S scores ≤2 and > 2 , respectively . Analyses were performed on the total anxiety ( GAD , SAD and PD ) and GAD groups . Results : During 1 year of treatment with pregabalin , dizziness ( 12.5 % ) was the only treatment-related adverse event ( AE ) occurring ≥10 % . Somnolence , weight gain , headache and insomnia occurred at 7.6 % , 5.5 % , 5.3 % and 4.7 % , respectively . Few treatment-related AEs were rated as severe in the total anxiety ( 5.1 % ) or GAD ( 3.6 % ) groups . Discontinuation rates due to AEs were similar ( 9.7 % and 10.6 % , respectively ) . No clinical ly significant laboratory , electrocardiogram , or other treatment-related safety findings were noted , except for treatment-related weight gain , which occurred in both the total ( 24.4 % ) and GAD ( 19.4 % ) groups . Mean CGI-S scores were similar at baseline in the total ( n = 528 ; score , 3.4 ) and GAD groups ( n = 330 ; score , 3.6 ) , and CGI-S responder rates were similar at last-observation-carried-forward endpoint ( 51.3 % and 48.1 % , respectively ) . Conclusions : Pregabalin was generally well tolerated in the long-term treatment of anxiety disorders . Improvement in illness severity was maintained over time . The key limitations of this study were that it was not r and omized and neither placebo- nor active-comparator-controlled

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

A Naturalistic Long-Term Comparison Study of Selective Serotonin Reuptake Inhibitors in the Treatment of Panic Disorder

Objectives : Selective serotonin reuptake inhibitors ( SSRIs ) are currently considered as the first drug of choice in the treatment of panic disorder ( PD ) . The aim of this long-term , naturalistic comparison study was to compare 4 SSRIs with respect to tolerability and treatment outcome of PD . Outcome measures included relapse rates and adverse effects . Methods : Two hundred patients with PD were enrolled in our study . All subjects met DSM-IV criteria for PD or PD with agoraphobia ( PDA ) . All patients were assigned to receive SSRI monotherapy for 12 months with either citalopram ( n = 50 ) , fluoxetine ( n = 50 ) , fluvoxamine ( n = 50 ) , or paroxetine ( n = 50 ) in a r and omized , nonblinded fashion . Both the treating psychiatrist and the patients were not blind to the assigned treatment , but the clinician raters were blind to the study medication . The study design allowed for assignment of a particular SSRI as indicated according to the clinical judgment of the study psychiatrists . The Panic Self- Question naire , which is a self-report scale , was administered at baseline and then once per month during the duration of the 12-month study . The visual analog scale and the Clinical Global Impression Scale were administered at baseline and then once per month during the period of the study . Reports of sexual dysfunction were assessed using a nonstructured clinical interview at monthly visits . The body weight of study subjects was measured at baseline , and then at the 12th month visit end point . Results : Of 200 patients who entered the study , 127 patients ( 63.5 % ) completed the full 12-month protocol . Retention rates were highest for paroxetine ( 76 % [ 38/50 ] ) , intermediate for citalopram ( 68 % [ 34/50 ] ) and fluvoxamine ( 60 % [ 30/50 ] ) , and lowest for fluoxetine ( 50 % [ 25/50 ] ) . Patients who completed the 12-month protocol responded favorably to the study treatment . The paroxetine and the citalopram groups had significantly lower rates of panic symptoms as measured at visits on weeks 4 and 8 . At visits on months 3 , 6 , 9 , and 12 , however , there were no statistically significant differences between the 4 groups in relapse rates ( defined as the occurrence of 1 or more panic attacks during the previous week of treatment ) ( F1,127 = 0.17 ; P = 0.13 [ not statistically significant ] ) . At the 12th month end point , patients in all 4 treatment groups had a statistically significant increase in body weight . Body weight among the study population increased by 6.1 + 4.9 kg from a mean weight of 72.4 + 7.3 kg at the onset of treatment . Reports of sexual adverse effects at the 12th month visit were similar in the citalopram , fluoxetine , and paroxetine groups , but the fluvoxamine patient group reported fewer sexual adverse effects at the 12th month visit . Conclusions : Most of our PD patients responded well to 12-month treatment with either citalopram , fluoxetine , fluvoxamine , or paroxetine , and the overall response rate was equal after the first 4 weeks of treatment . Although patients treated with paroxetine had the lowest dropout rates during the initiation phase , they had the highest rate of adverse effects as measured at the 12th month visit . Conversely , patients in the fluvoxamine group had the highest dropout rate ( which was primarily caused by adverse effects in the initiation phase of treatment . ) ; however , patients who were able to tolerate fluvoxamine throughout the full course of the study were observed to have lower rates of sexual dysfunction and weight gain compared with patients treated with the other agents . Overall , when measured at the 12th month visit , monotherapy with paroxetine and citalopram was associated with a higher rate of sexual adverse effects than was treatment with fluoxetine or fluvoxamine . In addition , monotherapy with paroxetine , citalopram , and fluoxetine seemed to cause more weight gain than did treatment with fluvoxamine

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Effects of extended-release quetiapine fumarate on long-term functioning and sleep quality in patients with Generalized Anxiety Disorder (GAD): data from a randomized-withdrawal, placebo-controlled maintenance study.

BACKGROUND This analysis evaluated effects of quetiapine XR maintenance treatment on functioning and sleep in patients with GAD . METHODS Analysis of patient-reported data from a r and omized-withdrawal , double-blind , placebo-controlled study of quetiapine XR monotherapy in GAD . Following open-label run-in ( 4 - 8 weeks ) and a 12 - 18-week stabilization phase ( quetiapine XR 50 , 150 , or 300 mg/day ) , eligible patients were r and omized to continue on quetiapine XR or receive placebo for up to 52 weeks . Primary variable was time to an anxiety event . Secondary variables included the Sheehan Disability Scale ( SDS ) and Pittsburgh Sleep Quality Index ( PSQI ) . RESULTS In total , 432 patients were r and omized ( quetiapine XR , N=216 ; placebo , N=216 ) . The risk of an anxiety event was significantly reduced for quetiapine XR vs. placebo ( HR 0.19 ; 95 % CI 0.12 , 0.31 ; p<0.001 ) . Quetiapine XR was more effective than placebo at maintaining SDS total scores ( LSM change : -0.19 vs. 1.01 ; p=0.017 ) and non-work-related SDS domain score ' family life/home responsibilities ' ( -0.13 vs. 0.32 ; p=0.011 ) , but not ' social life ' ( 0.05 vs. 0.34 ; p=0.114 ) . Quetiapine XR was more effective than placebo at maintaining the work-related SDS domain score ' days lost ' ( -0.05 vs. 0.11 ; p=0.027 ) , but not ' work/school ' ( -0.10 vs. 0.29 ; p=0.051 ) or ' days underproductive ' ( 0.06 vs. 0.13 ; p=0.619 ) . PSQI global scores were reduced from r and omization with quetiapine XR vs. placebo ( 0.39 vs. 1.60 ; p<0.001 ) . LIMITATIONS Lack of active-comparator arm , exclusion of patients with comorbid depression . CONCLUSIONS In patients with GAD , long-term treatment with quetiapine XR ( 50 - 300 mg/day ) monotherapy was effective at maintaining improvements in functioning and sleep quality

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

A comparison of citalopram and paroxetine in the treatment of panic disorder: a randomized, single-blind study.

BACKGROUND Serotonin Selective Re-uptake Inhibitors ( SSRIs ) are the drugs of choice for treating panic disorder ( PD ) . In vitro studies have shown different pharmacodynamic profiles for SSRIs , but their clinical relevance is still unknown . Paroxetine , the SSRI with the strongest serotonergic effect , also shows significant cholinergic and noradrenergic activities . In this class of drugs , citalopram is the most selective for serotonin . We compared these two drugs and their effectiveness and tolerability in a sample of patients with PD in a two-month treatment course . METHOD Fifty-eight patients with PD were r and omly assigned to either the paroxetine or the citalopram treatment group in a single-blind , r and omized design . Each patient was assessed at days 0 , 7 and 60 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Primary outcome measures were the percentage of patients free of panic attacks , anticipatory anxiety and phobic avoidance in the last week of the trial and the percentage of good responders , as defined by a reduction of at least 50 % from baseline of both PASS and SDS global scores at day 60 . RESULTS At day 60 , 86 % of patients receiving citalopram and 84 % of those receiving paroxetine responded well to treatment . No significant differences between the two drugs were found . Both were well tolerated , although sexual side effects and weight gain were frequent . Anticipatory anxiety decreased significantly after the first week of treatment , and no initial worsening in the panic attacks was observed . CONCLUSION Paroxetine and citalopram show similar anti-panic properties and a good tolerability profile . Our results support evidence that the serotonergic system plays a significant role in the anti-panic properties of these two SSRIs

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Antidepressant medication augmented with cognitive-behavioral therapy for generalized anxiety disorder in older adults.

OBJECTIVE Generalized anxiety disorder is common among older adults and leads to diminished health and cognitive functioning . Although antidepressant medications are efficacious , many elderly individuals require augmentation treatment . Furthermore , little is known about maintenance strategies for older people . The authors examined whether sequenced treatment combining pharmacotherapy and cognitive-behavioral therapy ( CBT ) boosts response and prevents relapse in older adults with generalized anxiety disorder . METHOD Participants were individuals at least 60 years of age with generalized anxiety disorder ( N=73 ) who were recruited from outpatient clinics at three sites . Participants received 12 weeks of open-label escitalopram and were then r and omly assigned to one of four conditions : 16 weeks of escitalopram ( 10 - 20 mg/day ) plus modular CBT , followed by 28 weeks of maintenance escitalopram ; escitalopram alone , followed by maintenance escitalopram ; escitalopram plus CBT , followed by pill placebo ; and escitalopram alone , followed by placebo . RESULTS Escitalopram augmented with CBT increased response rates on the Penn State Worry Question naire but not on the Hamilton Anxiety Rating Scale compared with escitalopram alone . Both escitalopram and CBT prevented relapse compared with placebo . CONCLUSIONS This study demonstrates effective strategies for treatment of generalized anxiety disorder in older adults . The sequence of antidepressant medication augmented with CBT leads to worry reduction in the short-term . Continued medication prevents relapse , but for many individuals , CBT would allow sustained remission without requiring long-term pharmacotherapy

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

Tapering Clonazepam in Patients With Panic Disorder After at Least 3 Years of Treatment

High-potency benzodiazepines , such as clonazepam , are frequently used in the treatment of panic disorder ( PD ) because of their rapid onset of action and good tolerability . However , there is concern about their potential to cause withdrawal symptoms . We aim ed to develop a protocol for safely tapering off clonazepam in patients with PD who had been receiving treatment for at least 3 years . A specific scale for judging withdrawal was also developed , the Composite Benzodiazepine Discontinuation Symptom Scale . We selected 73 patients with PD who had been asymptomatic for at least 1 year and who wished to discontinue the medication . The trial consisted of a 4-month period of tapering and an 8-month follow-up period . The dosage of clonazepam was decreased by 0.5 mg per 2-week period until 1 mg per day was reached , followed by a decrease of 0.25 mg per week . The mean dosage at the start of tapering was 2.7 ± 1.2 mg/d . In total , 51 ( 68.9 % ) of the patients were free of the medication after the 4 months of tapering according to the protocol , and 19 ( 26.0 % ) of the patients needed another 3 months to be free of medication . Clonazepam discontinuation symptoms were mostly mild and included mainly : anxiety , shaking/trembling/tremor , nausea/vomiting , insomnia/nightmares , excessive sweating , tachycardia/palpitations , headache , weakness , and muscle aches . The improvement in PD and general well-being was maintained during both the taper and follow-up phases . Clonazepam can be successfully discontinued without any major withdrawal symptoms if the dose is reduced gradually . We recommend reducing the dosage of clonazepam after intermediate-term use by 0.25 mg/wk

Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy . Paroxetine , escitalopram , and clonazepam can be effective for long-term treatment of PD . Pregabalin and quetiapine can be effective for long-term treatment of GAD , while preliminary suggestions emerged for agomelatine and vortioxetine . We did not find any evidence for determining the optimal length and /or dosage of medications to minimize the relapse risk .

Many aspects of long-term pharmacological treatments for anxiety disorders ( AnxDs ) are still debated . We undertook an up date d systematic review of long-term pharmacological studies on panic disorder ( PD ) , generalized anxiety disorder ( GAD ) , and social anxiety disorder ( SAD ) .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial

Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation ( AF ) . We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation . Methods and results Patients r and omized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ( ROCKET-AF ) trial ( n = 14 264 ) were grouped by baseline AF category : paroxysmal or persistent . Multivariable adjustment was performed to compare thrombo-embolic events , bleeding , and death between groups , in high-risk subgroups , and across treatment assignment ( rivaroxaban or warfarin ) . Of 14 062 patients , 11 548 ( 82 % ) had persistent AF and 2514 ( 18 % ) had paroxysmal AF . Patients with persistent AF were marginally older ( 73 vs. 72 , P = 0.03 ) , less likely female ( 39 vs. 45 % , P < 0.0001 ) , and more likely to have previously used vitamin K antagonists ( 64 vs. 56 % , P < 0.0001 ) compared with patients with paroxysmal AF . In patients r and omized to warfarin , time in therapeutic range was similar ( 58 vs. 57 % , P = 0.94 ) . Patients with persistent AF had higher adjusted rates of stroke or systemic embolism ( 2.18 vs. 1.73 events per 100-patient-years , P = 0.048 ) and all-cause mortality ( 4.78 vs. 3.52 , P = 0.006 ) . Rates of major bleeding were similar ( 3.55 vs. 3.31 , P = 0.77 ) . Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment ( rivaroxaban vs. warfarin , Pinteraction = 0.6 ) . Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation , those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Risk of Early Death and Recurrent Stroke and Effect of Heparin in 3169 Patients With Acute Ischemic Stroke and Atrial Fibrillation in the International Stroke Trial

Background and Purpose — We sought to investigate the apparently high risk of early death after an ischemic stroke among patients with atrial fibrillation ( AF ) , identify the main factors associated with early death , and assess the effect of treatment with different doses of subcutaneous unfractionated heparin ( UFH ) given within 48 hours . Methods — We studied the occurrence of major clinical events within 14 days among 18 451 patients from the International Stroke Trial , first for all treatment groups combined . Then , among patients with AF , we examined the effects of treatment with subcutaneous UFH started within 48 hours and continued until 14 days after stroke onset . Results — A total of 3169 patients ( 17 % ) had AF . Seven hundred eighty-four patients were allocated to UFH 12 500 IU SC BID , 773 to UFH 5000 IU SC BID , and 1612 to no heparin . Within each of these groups , half of the patients were r and omly assigned to aspirin 300 mg once daily . Compared with patients without AF , patients with AF were more likely to be female ( 56 % versus 45 % ) , to be old ( mean age , 78 versus 71 years ) , to have an infa rct on prer and omization CT ( 57 % versus 47 % ) , and to have impaired consciousness ( 37 % versus 20 % ) . The initial ischemic stroke type was more often a large-artery infa rct ( 36 % versus 21 % ) . A lacunar stroke syndrome was less common ( 13 % versus 26 % ) . Death within 14 days was more common in patients with AF ( 17 % versus 8 % ) and more often attributed to neurological damage from the initial stroke ( 10 % versus 4 % ) . The frequency of recurrent ischemic or undefined stroke was not significantly different ( 3.9 % versus 3.3 % ) . The proportion of AF patients with further events within 14 days allocated to UFH 12 500 IU ( n=784 ) , UFH 5000 IU ( n=773 ) , and to no-heparin ( n=1612 ) groups were as follows : ischemic stroke , 2.3 % , 3.4 % , 4.9 % ( P = 0.001 ) ; hemorrhagic stroke , 2.8 % , 1.3 % , 0.4 % ( P < 0.0001 ) ; and any stroke or death , 18.8 % , 19.4 % and 20.7 % ( P = 0.3 ) , respectively . No effect of heparin on the proportion of patients dead or dependent at 6 months was apparent . Conclusions — Acute ischemic stroke patients with AF have a higher risk of early death , which can be explained by older age and larger infa rcts but not by a higher risk of early recurrent ischemic stroke , although slightly more patients with AF died from a fatal recurrent stroke of ischemic or unknown type ( 1.3 % versus 0.9 % ) . In patients with AF the absolute risk of early recurrent stroke is low , and there is no net advantage to treatment with heparin . These data do not support the widespread use of intensive heparin regimens in the acute phase of ischemic stroke associated with AF

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Atrial flutter: Clinical risk factors and adverse outcomes in the Framingham Heart Study.

BACKGROUND Few epidemiologic cohort studies have evaluated atrial flutter ( flutter ) as an arrhythmia distinct from atrial fibrillation ( AF ) . OBJECTIVE The purpose of this study was to examine the clinical correlates of flutter and its associated outcomes to distinguish them from those associated with AF in the Framingham Heart Study . METHODS We review ed and adjudicated electrocardiograms ( ECGs ) previously classified as flutter or AF/flutter and another 100 ECGs r and omly selected from AF cases . We examined the clinical correlates of flutter by matching up to 5 AF and 5 referents to each flutter case using a nested case referent design . We determined the 10-year outcomes associated with flutter with Cox models . RESULTS During mean follow-up of 33.0 ± 12.2 years , 112 participants ( mean age 72 ± 10 years , 30 % women ) developed flutter . In multivariable analyses , smoking ( odds ratio [ OR ] 2.84 , 95 % confidence interval [ CI ] 1.54 - 5.23 ) , increased PR interval ( OR 1.28 per SD , 95 % CI 1.03 - 1.60 ) , myocardial infa rct ion ( OR 2.25 , 95 % CI 1.05 - 4.80 ) and heart failure ( OR 5.22 , 95 % CI 1.26 - 21.64 ) were associated with incident flutter . In age- and sex-adjusted models , flutter ( vs referents ) was associated with 10-year increased risk of AF ( hazard ratio [ HR ] 5.01 , 95 % CI 3.14 - 7.99 ) , myocardial infa rct ion ( HR 3.05 , 95 % CI 1.42 - 6.59 ) , heart failure ( HR 4.14 , 95 % CI 1.90 - 8.99 ) , stroke ( HR 2.17 , 95 % CI 1.13 - 4.17 ) , and mortality ( HR 2.00 , 95 % CI 1.44 - 2.79 ) . CONCLUSION We identified the clinical correlates associated with flutter and observed that flutter was associated with multiple adverse outcomes

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Causes of Death and Influencing Factors in Patients With Atrial Fibrillation: A Competing-Risk Analysis From the Randomized Evaluation of Long-Term Anticoagulant Therapy Study

Background — Atrial fibrillation is associated with increased mortality , but the specific causes of death and their predictors have not been described among patients on effective anticoagulant therapy . Methods and Results — The R and omized Evaluation of Long-Term Anticoagulant Therapy ( RE-LY ) trial r and omized 18 113 patients ( age , 71.5±9 years ; male , 64 % ; CHADS2 score , 2.1±1 ) to receive dabigatran or warfarin . Median follow-up was 2 years , and complete follow-up was achieved in 99.9 % of patients . All deaths were categorized by the investigators using prespecified definitions followed by central adjudication . Overall , 1371 deaths occurred ( annual mortality rate , 3.84 % ; 95 % confidence interval [ CI ] , 3.64–4.05 ) . Cardiac deaths ( sudden cardiac death and progressive heart failure ) accounted for 37.4 % of all deaths , whereas stroke- and hemorrhage-related deaths represented 9.8 % of the total mortality . An examination of the causes of death according to dabigatran or warfarin showed that dabigatran significantly reduced vascular ( embolism and hemorrhage-related ) mortality ( relative risk , 0.63 ; 95 % CI , 0.45–0.88 ; P=0.007 ) , whereas other causes of death were similar between treatments , including cardiac mortality ( relative risk , 0.96 ; 95 % CI , 0.80–1.15 ; P=0.638 ) . The two strongest independent predictors of cardiac death in this population were heart failure ( hazard ratio , 3.02 ; 95 % CI , 2.45–3.73 ; P<0.0001 ) , and prior myocardial infa rct ion ( hazard ratio , 2.05 ; 95 % CI , 1.61–2.62 ; P<0.0001 ) . Conclusions — The majority of deaths are not related to stroke in a contemporary anticoagulated atrial fibrillation population . These results emphasize the need to identify interventions beyond effective anticoagulation to further reduce mortality in atrial fibrillation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00262600

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Myocardial Ischemic Events in Patients With Atrial Fibrillation Treated With Dabigatran or Warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) Trial

Background — There is a modest risk of myocardial infa rct ion ( MI ) and myocardial ischemic events in patients with atrial fibrillation . Methods and Results — Data from the RE-LY study ( R and omized Evaluation of Long-Term Anticoagulation Therapy ) were used to report rates of MI , unstable angina , cardiac arrest , and cardiac death and the prespecified net clinical benefit and treatment effects of dabigatran versus warfarin . MI occurred at annual rates of 0.82 % and 0.81 % with dabigatran 110 or 150 mg BID compared with 0.64 % with warfarin ( hazard ratio [ HR ] 1.29 , 95 % confidence interval [ CI ] 0.96–1.75 , P=0.09 for dabigatran 110 mg ; HR 1.27 , 95 % CI 0.94–1.71 , P=0.12 for dabigatran 150 mg ) . Annual rates of a composite of MI , unstable angina , cardiac arrest , and cardiac death were 3.16 % per year with dabigatran 110 mg , 3.33 % per year with dabigatran 150 mg , and 3.41 % per year with warfarin ( HR versus warfarin 0.93 , 95 % CI 0.80–1.06 , P=0.28 for dabigatran 110 mg and HR 0.98 , 95 % CI 0.85–1.12 , P=0.77 for dabigatran 150 mg ) . Events prespecified as “ net clinical benefit ” ( all strokes , systemic embolism , MI , pulmonary embolism , major bleeding , and all-cause death ) occurred at a rate of 7.34 % per year with dabigatran 110 mg , 7.11 % per year with dabigatran 150 mg , and 7.91 % per year with warfarin ( HR 0.92 , 95 % CI 0.84–1.01 , P=0.09 for dabigatran 110 mg and HR 0.90 , 95 % CI 0.82–0.99 , P=0.02 for dabigatran 150 mg ) . The relative effects of dabigatran versus warfarin on myocardial ischemic events were consistent in patients with or without a baseline history of MI or coronary artery disease . Conclusions — There was a nonsignificant increase in MI with dabigatran compared with warfarin , but other myocardial ischemic events were not increased . Treatment effects of dabigatran were consistent in patients at higher and lower risk of myocardial ischemic events . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT 00262600

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Aortic plaque in atrial fibrillation: prevalence, predictors, and thromboembolic implications.

BACKGROUND AND PURPOSE Thoracic aortic plaque identified by transesophageal echocardiography heightens the risk of stroke associated with atrial fibrillation ( AF ) . We sought to identify the prevalence , predictors , and implication s of aortic plaque in patients with nonvalvular AF . METHODS Thoracic aortic plaque was prospect ively sought in 770 persons with AF with the use of transesophageal echocardiography and classified as simple or complex on the basis of thickness > /=4 mm , ulceration , or mobility . Clinical and echocardiographic features of thromboembolism were correlated by multivariate analysis . RESULTS Aortic plaque was detected in 57 % of the cohort , and complex plaque was detected in 25 % . Both were found more frequently in the descending than in the proximal aorta . Potentially etiologic patient characteristics independently associated with complex plaque included advanced age , history of hypertension , diabetes , and past or present tobacco use . Comorbidities associated with aortic plaque were prior thromboembolism , increased pulse pressure , ischemic heart disease , stenosis or sclerosis of the aortic valve , mitral annular calcification ( > 10 % ) , elevated serum creatinine concentration , spontaneous echo contrast in the left atrium or appendage , and left atrial appendage thrombus . The prevalence of complex plaque in patients aged < 70 years with < 10 % mitral annular calcification , without ischemic heart disease , or without pulse pressure > /=65 mm Hg was 4 % ( 95 % CI , 1 % to 6 % ) . CONCLUSIONS Aortic plaque is prevalent in patients with AF and is associated with atherosclerosis risk factors and with left atrial stasis or thrombosis , which are themselves independent stroke risk factors . Since the predominant location of complex plaque was in the descending aorta , the role of aortic plaque as a source of embolism in AF is uncertain

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Atrial fibrillation and the risk of myocardial infarction.

IMPORTANCE Myocardial infa rct ion ( MI ) is an established risk factor for atrial fibrillation ( AF ) . However , the extent to which AF is a risk factor for MI has not been investigated . OBJECTIVE To examine the risk of incident MI associated with AF . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve cohort of 23,928 participants residing in the continental United States and without coronary heart disease at baseline were enrolled from the Reasons for Geographic and Racial Differences in Stroke ( REGARDS ) cohort between 2003 and 2007 , with follow-up through December 2009 . MAIN OUTCOMES AND MEASURES Expert-adjudicated total MI events ( fatal and nonfatal ) . RESULTS Over 6.9 years of follow-up ( median 4.5 years ) , 648 incident MI events occurred . In a sociodemographic-adjusted model , AF was associated with about 2-fold increased risk of MI ( hazard ratio [ HR ] , 1.96 [ 95 % CI , 1.52 - 2.52 ] ) . This association remained significant ( HR , 1.70 [ 95 % CI , 1.26 - 2.30 ] ) after further adjustment for total cholesterol , high-density lipoprotein cholesterol , smoking status , systolic blood pressure , blood pressure-lowering drugs , body mass index , diabetes , warfarin use , aspirin use , statin use , history of stroke and vascular disease , estimated glomerular filtration rate , albumin to creatinine ratio , and C-reactive protein level . In subgroup analysis , the risk of MI associated with AF was significantly higher in women ( HR , 2.16 [ 95 % CI , 1.41 - 3.31 ] ) than in men ( HR , 1.39 [ 95 % CI , 0.91 - 2.10 ] ) and in blacks ( HR , 2.53 [ 95 % CI , 1.67 - 3.86 ] ) than in whites ( HR , 1.26 [ 95 % CI , 0.83 - 1.93 ] ) ; for interactions , P = .03 and P = .02 , respectively . On the other h and , there were no significant differences in the risk of MI associated with AF in older ( ≥75 years ) vs younger ( < 75 years ) participants ( HR , 2.00 [ 95 % CI , 1.16 - 3.35 ] and HR , 1.60 [ 95 % CI , 1.11 - 2.30 ] , respectively ) ; for interaction , P = .44 . CONCLUSIONS AND RELEVANCE AF is independently associated with an increased risk of incident MI , especially in women and blacks . These findings add to the growing concerns of the seriousness of AF as a public health burden : in addition to being a well-known risk factor for stroke , AF is also associated with increased risk of MI

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Hemodynamic effects of an irregular sequence of ventricular cycle lengths during atrial fibrillation.

OBJECTIVES The aim of this study was to determine the independent hemodynamic effects of an irregular sequence of ventricular cycle lengths in patients with atrial fibrillation ( AF ) . BACKGROUND Atrial fibrillation may reduce cardiac output by several possible mechanisms , including loss of the atrial contribution to left ventricular filling , valvular regurgitation , increased ventricular rate or irregular RR intervals . This study was design ed to evaluate the effects of an irregular RR interval , independent of the average ventricular rate , on cardiac hemodynamic data during AF . METHODS Sixteen patients with AF were studied invasively . During intrinsically conducted AF ( mean rate 102 + /- 22 beats/ min ) , the right ventricular apex electrogram was recorded onto frequency-modulated ( FM ) tape . After atrioventricular node ablation , the right ventricular apex was stimulated in three pacing modes in r and omized sequence : 1 ) VVI at 60 beats/min ; 2 ) VVI at the same average rate as during intrinsically conducted AF ( 102 + /- 22 beats/min ) ; and 3 ) during VVT pacing in which the pacemaker was triggered by playback of the FM tape recording of the right ventricular apex electrogram previously recorded during intrinsically conducted AF ( VVT 102 + /- 22 beats/min ) . RESULTS Compared with VVI pacing at the same average rate , an irregular sequence of RR intervals decreased cardiac output ( 4.4 + /- 1.6 vs. 5.2 + /- 2.4 liters/min , p < 0.01 ) , increased pulmonary capillary wedge pressure ( 17 + /- 7 vs. 14 + /- 6 mm Hg , p < 0.002 ) and increased right atrial pressure ( 10 + /- 6 vs. 8 + /- 4 mm Hg , p < 0.05 ) . CONCLUSIONS An irregular sequence of RR intervals produces adverse hemodynamic consequences that are independent of heart rate

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Risk of Myocardial Infarction or Vascular Death After First Ischemic Stroke: The Northern Manhattan Study

Background and Purpose — In national guidelines , absolute long-term risk of myocardial infa rct ion ( MI ) or coronary death determines target low-density lipoprotein levels , but stroke patients are not explicitly addressed . We determined the absolute 5-year risk of cardiovascular outcomes and their predictors after first ischemic stroke in a multiethnic cohort . Methods — A population -based cohort of first ischemic stroke patients ≥40 years old was prospect ively followed annually for recurrent stroke , MI and cause-specific mortality . Kaplan-Meier 5-year risks for MI or vascular death ( primary outcome ) , and other cardiovascular events , were calculated . Univariate and multivariate Cox proportional hazards models were used to calculate hazard ratios and 95 % CI for predictors of cardiovascular outcomes . Results — Mean age ( n=655 ) was 69.7±12.7 years ; 55.4 % of participants were women , and 51.3 % Hispanic . The 5-year risk of MI or vascular death was 17.4 % ( 95 % CI , 14.2 % to 20.6 % ) . Independent historical predictors of MI or vascular death were age > 70 years ( hazard ratio 1.62 , 1.07 to 2.44 ) , history of coronary artery disease ( hazard ratio 1.76 , 1.13 to 2.74 ) , and atrial fibrillation ( hazard ratio 1.76 , 1.05 to 2.94 ) . In the lowest risk group , those ≤70 years old without coronary artery disease , 5-year risk of MI or vascular death was 9.7 % . Conclusions — The absolute risk of MI or vascular death after ischemic stroke , even in those without high-risk features , approximates levels used by national organizations to design ate groups of patients at high risk of vascular events . The comparability of levels of absolute risk among stroke and cardiac patients may have treatment implication

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Predictors of major adverse cardiovascular events; results of population based MELEN study with prospective follow-up.

OBJECTIVE In healthy persons , cardiovascular risk is the result of multiple interacting risk associates including demographic , clinical , genetic and environmental factors . Several non-invasive tools such as echocardiography , ultrasonography and electrocardiography as well as new biochemical markers were shown to be applicable to predict cardiovascular events . However , implementation of all of these tools has not been tested before . The aim of the study was to evaluate the independent predictors of major adverse cardiovascular events in a prospect i ve population based study , with the use of bioempedance analysis , echocardiography , ultrasonography and ECG . PATIENTS AND METHODS The baseline measurements were conducted on 2230 participants ( 1427 women , 803 men with a mean age of 49 ± 15 ) . The follow-up was done 36 months after the baseline admission via telephone call . Major adverse event was defined as mortality or myocardial infa rct ion or stroke . RESULTS Follow-up data was possible in 1495 participants ( 65 % ) . During the follow-up of 36 months ( 4485 patient years ) , 42 major adverse events occurred ( 0.03 % ) . Among them , 16 were death ( 1 stroke , 2 cancer , 13 cardiac related ) , 12 were stroke and 14 were myocardial infa rct ion . Age , body mass index and atrial fibrillation were independent predictors of major adverse events ; AF being the most powerful ( Odds ratio 10.46 ; 95 % confidence interval [ 1.73 - 63.14 ] ; p = 0.010 ) . CONCLUSIONS Age , lower body mass index and atrial fibrillation were independent predictors of major cardiovascular events in our cohort

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Acute myocardial infarction in patients with atrial fibrillation with a CHA2DS2-VASc score of 0 or 1: a nationwide cohort study.

BACKGROUND The risk of acute myocardial infa rct ion ( AMI ) in patients with atrial fibrillation ( AF ) with a CHA2DS2-VASc score of 0 ( for men ) or 1 ( for women ) has not been previously investigated . OBJECTIVE The objective of the present study was to compare the risk of AMI in AF and non-AF subjects with a low ( 0 or 1 ) CHA2DS2-VASc score . METHODS By using the National Health Insurance Research Data base in Taiwan , we identified 7254 men with AF ( with a CHA2DS2-VASc score of 0 ) and 4860 women with AF ( with a CHA2DS2-VASc score of 1 ) . For each study patient , 1 age- , sex- , and CHA2DS2-VASc score-matched subject without AF was r and omly selected to constitute the control group ( n = 12,114 ) . The clinical end point was the occurrence of AMI . RESULTS During a mean follow-up period of 5.7 ± 3.6 years , 258 patients ( 1.1 % ) suffered an AMI , with an annual incidence of 0.29 % and 0.10 % for patients with and without AF . AF was an independent risk factor of AMI , with an adjusted hazard ratio ( HR ) of 2.93 ( 95 % confidence interval 2.21 - 3.87 ; P < .001 ) . The risk of AMI was higher in men with AF than in women with AF , with a hazard ratio of 2.24 ( 95 % confidence interval 1.61 - 3.11 ; P < .001 ) after adjustment for age and other comorbidities . CONCLUSION In patients with a CHA2DS2-VASc score of 0 or 1 , AF was an independent risk factor of AMI . The risk of AMI was higher in men with AF than in women with AF . Cardiovascular risk prevention should be performed as part of the holistic management of AF to minimize the risks of AMI associated with AF

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Atrial fibrillation and mortality in an elderly population.

Prospect i ve data from Busselton , Western Australia , collected during triennial surveys from 1966 - 81 with follow-up of subjects to 1983 , showed that atrial fibrillation ( AF ) was frequent in elderly people and associated with increased mortality . Of 1770 people aged over 60 years , 40 were in atrial fibrillation when first seen and a further 47 developed it during follow-up . Atrial fibrillation was positively associated with angina , history of a myocardial infa rct ion and left bundle branch block . Relative mortality in those with atrial fibrillation compared with those without it , was 1.92 for all causes , 1.82 for death from cardiovascular causes ( excluding stroke ) and 3.78 for deaths from stroke , after adjustment by proportional hazards regression for confounding effects of age , sex , history of a myocardial infa rct ion , an abnormal electrocardiogram , angina , cholesterol level systolic blood pressure and Quetelet 's Index ( weight/height2 ) . The excess relative mortality declined with increasing age for both women and men . This raised relative mortality remained constant with time from the first detection of AF for all causes and cardiovascular causes but appeared to increase with time from detection for stroke death . The risk of death from stroke was greatest in the younger women . The observed risk of death from stroke in patients with AF suggests that anticoagulant use should be considered in selected patients

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of Left Ventricular Dysfunction.

OBJECTIVE This study undertook to determine if the presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular dysfunction was associated with increased mortality and , if so , whether the increase could be attributed to progressive heart failure or arrhythmic death . BACKGROUND Atrial fibrillation is a common condition in heart failure with the potential to impact hemodynamics and progression of left ventricular systolic dysfunction as well as the electrophysiologic substrate for arrhythmias . The available data do not conclusively define the effect of atrial fibrillation on prognosis in heart failure . METHODS A retrospective analysis of the Studies of Left Ventricular Dysfunction Prevention and Treatment Trials was conducted that compared patients with atrial fibrillation to those in sinus rhythm at baseline for the risk of all-cause mortality , progressive pump-failure death and arrhythmic death . RESULTS The patients with atrial fibrillation at baseline , compared to those in sinus rhythm , had greater all-cause mortality ( 34 % vs. 23 % , p < 0.001 ) , death attributed to pump-failure ( 16.7 % vs. 9.4 % , p < 0.001 ) and were more likely to reach the composite end point of death or hospitalization for heart failure ( 45 % vs. 33 % , p < 0.001 ) , but there was no significant difference between the groups in arrhythmic deaths . After multivariate analysis , atrial fibrillation remained significantly associated with all-cause mortality ( relative risk [ RR ] 1.34 , 95 % confidence interval [ CI ] 1.12 to 1.62 , p=0.002 ) , progressive pump-failure death ( RR 1.42 , 95 % CI 1.09 to 1.85 , p=0.01 ) , the composite end point of death or hospitalization for heart failure ( RR 1.26 , 95 % CI 1.03 to 1.42 , p=0.02 ) , but not arrhythmic death ( RR 1.13 ; 95 % CI 0.75 to 1.71 ; p=0.55 ) . CONCLUSIONS The presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular systolic dysfunction is associated with an increased risk for all-cause mortality , largely explained by an increased risk for pump-failure death . These data suggest that atrial fibrillation is associated with progression of left ventricular systolic dysfunction

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Incidence of myocardial infarction and vascular death in elderly patients with atrial fibrillation taking anticoagulants: relation to atherosclerotic risk factors.

BACKGROUND Recent findings suggest that patients with atrial fibrillation ( AF ) , in addition being at thromboembolic risk , are at risk of myocardial infa rct ion ( MI ) . Our aim was to investigate predictors of MI and cardiovascular death in a cohort of patients with AF who were taking anticoagulants . METHODS We prospect ively followed up 1,019 patients with AF for a median of 33.7 months ( 3,223 person-years ) . All patients were treated with oral vitamin K antagonists . Primary outcome was a composite end point of cardiovascular events ( CVEs ) including fatal/nonfatal MI , cardiac revascularization , and cardiovascular death . RESULTS The mean age of the patients was 73.2 years , and 43.8 % were women . At follow-up , 111 CVEs ( 3.43%/y ) had occurred : 47 fatal-nonfatal MI/revascularization and 64 cardiovascular deaths . In addition , 31 stroke/transient ischemic attacks ( 0.96%/y ) were recorded . Patients experiencing CVEs were older ( P < .001 ) and had a higher prevalence of metabolic syndrome ( MetS ) ( P = .005 ) , heart failure ( P = .001 ) , and prior cardiac ( P < .001 ) and cerebrovascular events ( P < .001 ) . On a Cox proportional hazard analysis , age ( hazard ratio [ HR ] , 1.083 ; 95 % CI , 1.053 - 1.113 ; P < .001 ) , smoking ( HR , 2.158 ; 95 % CI , 1.193 - 3.901 ; P = .011 ) , history of cerebrovascular ( HR , 1.704 ; 95 % CI , 1.119 - 2.597 ; P = .013 ) and cardiac ( HR , 1.658 ; 95 % CI , 1.105 - 2.489 ; P = .015 ) events , MetS ( HR , 1.663 ; 95 % CI , 1.107 - 2.499 ; P = .014 ) , heart failure ( HR , 1.584 ; 95 % CI , 1.021 - 2.456 ; P = .040 ) , and male sex ( HR , 1.499 ; 95 % CI , 1.010 - 2.223 ; P = .044 ) predicted CVEs . CONCLUSIONS Patients with AF still experience a high rate of CVEs despite receiving anticoagulant treatment . MetS is a common clinical feature in patients with AF , which increases the risk of CVEs . A holistic approach is needed to reduce the cardiovascular risk in patients with AF . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT01882114 ; URL : www . clinical trials.gov

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Risk of death and cardiovascular events in initially healthy women with new-onset atrial fibrillation.

CONTEXT The risks associated with new-onset atrial fibrillation ( AF ) among middle-aged women and population s with a low comorbidity burden are poorly defined . OBJECTIVES To examine the association between incident AF and mortality in initially healthy women and to evaluate the influence of associated cardiovascular comorbidities on risk . DESIGN , SETTING , AND PARTICIPANTS Between 1993 and March 16 , 2010 , 34,722 women participating in the Women 's Health Study underwent prospect i ve follow-up . Participants were 95 % white , older than 45 years ( median , 53 [ interquartile range { IQR } , 49 - 59 ] years ) , and free of AF and cardiovascular disease at baseline . Cox proportional hazards models with time-varying covariates were used to determine the risk of events among women with incident AF . Secondary analyses were performed among women with paroxysmal AF . MAIN OUTCOME MEASURES Primary outcomes included all-cause , cardiovascular , and noncardiovascular mortality . Secondary outcomes included stroke , congestive heart failure , and myocardial infa rct ion . RESULTS During a median follow-up of 15.4 ( IQR , 14.7 - 15.8 ) years , 1011 women developed AF . Incidence rates per 1000 person-years among women with and without AF were 10.8 ( 95 % confidence interval [ CI ] , 8.1 - 13.5 ) and 3.1 ( 95 % CI , 2.9 - 3.2 ) for all-cause mortality , 4.3 ( 95 % CI , 2.6 - 6.0 ) and 0.57 ( 95 % CI , 0.5 - 0.6 ) for cardiovascular mortality , and 6.5 ( 95 % CI , 4.4 - 8.6 ) and 2.5 ( 95 % CI , 2.4 - 2.6 ) for noncardiovascular mortality , respectively . In multivariable models , hazard ratios ( HRs ) of new-onset AF for all-cause , cardiovascular , and noncardiovascular mortality were 2.14 ( 95 % CI , 1.64 - 2.77 ) , 4.18 ( 95 % CI , 2.69 - 6.51 ) , and 1.66 ( 95 % CI , 1.19 - 2.30 ) , respectively . Adjustment for nonfatal cardiovascular events potentially on the causal pathway to death attenuated these risks , but incident AF remained associated with all mortality components ( all-cause : HR , 1.70 [ 95 % CI , 1.30 - 2.22 ] ; cardiovascular : HR , 2.57 [ 95 % CI , 1.63 - 4.07 ] ; and noncardiovascular : HR , 1.42 [ 95 % CI , 1.02 - 1.98 ] ) . Among women with paroxysmal AF ( n = 656 ) , the increase in mortality risk was limited to cardiovascular causes ( HR , 2.94 ; 95 % CI , 1.55 - 5.59 ) . CONCLUSION Among a group of healthy women , new-onset AF was independently associated with all-cause , cardiovascular , and noncardiovascular mortality , with some of the risk potentially explained by nonfatal cardiovascular events

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with atherothrombosis.

BACKGROUND Atrial fibrillation ( AF ) is a major risk factor ( RF ) for ischemic stroke . Its prevalence and prognostic impact in patients with atherothrombosis are unclear . METHODS Risk factors , drug usage , and 1-year cardiovascular ( CV ) outcomes ( CV death , myocardial infa rct ion [ MI ] , and stroke ) were compared in AF and non-AF patients from the REduction of Atherothrombosis for Continued Health ( REACH ) Registry , an international , prospect i ve cohort of 68,236 stable out patients with established atherothrombosis or > or=3 atherothrombotic RFs . RESULTS Atrial fibrillation and 1-year follow-up data are available for 63,589 patients . The prevalence of AF was , 12.5 % , 13.7 % , 11.5 % , and 6.2 % among coronary artery disease , CV disease , peripheral artery disease , and RF-only patients , respectively . Of the 6,814 patients with AF , 6.7 % experienced CV death , nonfatal MI , or nonfatal stroke within a year . The annual incidence of nonfatal stroke ( 2.4 % vs 1.6 % , P<.0001 ) and unstable angina ( 6.0 % vs 4.0 % , P<.00001 ) was higher , and CV death was more than double ( 3.2 % vs 1.4 % , P<.0001 ) , in AF versus non-AF patients . In these patients with or at high risk of atherothrombosis , most patients with AF received antiplatelet agents , but only 53.1 % were treated with oral anticoagulants . Even with high CHADS2 ( congestive heart failure , hypertension , aging , diabetes mellitus , and stroke ) scores , anticoagulant use did not exceed ( 59 % ) . The rate of bleeding requiring hospitalization was higher in AF versus non-AF patients ( 1.5 % vs 0.8 % , P<.0001 ) , possibly related to the more frequent use of anticoagulants ( 53.1 % vs 7.1 % ) . CONCLUSIONS Atrial fibrillation is common in patients with atherothrombosis , associated with more frequent fatal and nonfatal CV outcomes , and underuse of oral anticoagulants

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

Chronic atrial fibrillation--epidemiologic features and 14 year follow-up: a case control study.

In a r and omly selected population of 9067 individuals , 32 - 64 years of age in 1967 - 1970 , 25 ( 0.28 % ) had chronic atrial fibrillation ( CAF ) . Eight had lone atrial fibrillation . In 1984 the cases were compared with an age- and sex-matched control group of 50 and found to have more cerebrovascular accidents ( 6 versus 2 ; P less than 0.05 ) , congestive heart failure ( 9 versus 1 ; P less than 0.001 ) , and valvular rheumatic heart disease ( 3 versus 0 ) or history consistent with rheumatic fever ( 6 versus 0 ; P less than 0.01 ) . The mortality in the CAF group was 60 % higher due to an excess in cardiovascular ( relative risk 6.1 ; P less than 0.05 ) and cerebrovascular ( relative risk 12.2 ; P less than 0.05 ) causes . The prevalence or incidence of ischaemic or hypertensive heart disease or the presence of coronary risk factors did not significantly differ in the two groups . By M-mode echocardiography the left atrial size , left ventricular enddiastolic dimension and left ventricular mass were increased in the CAF patients , while the systolic left ventricular shortening was significantly less . Thus , the prevalence of CAF is low in a r and omly selected population 32 - 64 years of age and CAF is not strongly associated with ischaemic heart disease or hypertension . The CAF patients have an increased risk of dying prematurely particularly from cerebrovascular causes , even in the absence of valve disease

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

The association between atrial fibrillation and sudden cardiac death: the relevance of heart failure.

OBJECTIVES The purpose of this study was to evaluate the role of congestive heart failure ( CHF ) in the association between atrial fibrillation ( AF ) and sudden cardiac death ( SCD ) . BACKGROUND Recent studies have reported the possibility of an independent association between AF and SCD . We hypothesized that a history of CHF is a significant confounder of this association . METHODS In a prospect i ve case-control analysis from the community ( The Oregon-SUDS [ Sudden Unexpected Death Study ] , 2002 to 2012 ) , SCD cases ( n = 652 ) with clinical records available ( including electrocardiography and /or echocardiography ) were compared with age- and sex-matched control patients with coronary artery disease . The association between AF and SCD was analyzed using multivariable logistic regression and propensity score matching . RESULTS Cases ( age 67.3 ± 11.7 years , 65 % male ) were more likely than control patients ( age 67.2 ± 11.4 years , 65 % male ) to have a history of AF ( p = 0.0001 ) , myocardial infa rct ion ( p = 0.007 ) , CHF ( p < 0.0001 ) , stroke ( p < 0.0001 ) , and diabetes ( p < 0.0001 ) . In multivariate analysis without considering CHF , AF was a significant predictor of SCD ( odds ratio [ OR ] : 1.6 ; 95 % confidence interval [ CI ] : 1.2 to 2.0 ; p = 0.002 ) . However , in a model that included CHF , the AF-SCD association was no longer significant ( OR : 1.1 ; 95 % CI : 0.8 to 1.5 ; p = 0.45 ) , whereas CHF was a significant predictor of SCD ( OR : 3.1 ; 95 % CI : 2.4 to 4.1 ; p < 0.0001 ) . Results on the basis of propensity score matching were consistent . CONCLUSIONS Our findings suggest that a history of CHF , including both systolic and diastolic symptomatic dysfunction , may partially explain the AF-SCD association

These results showed that AF is an independent risk factor for MI , CV death , and CV events

This study aim ed to investigate whether atrial fibrillation ( AF ) predicts myocardial infa rct ion ( MI ) or cardiovascular ( CV ) death . AF is a well-established risk factor for thrombotic stroke and all-cause mortality .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Components of the indirect effect in vaccine trials: identification of contagion and infectiousness effects.

Vaccination of one person may prevent the infection of another either because the vaccine prevents the first from being infected and from infecting the second , or because , even if the first person is infected , the vaccine may render the infection less infectious . We might refer to the first of these mechanisms as a contagion effect and the second as an infectiousness effect . In the simple setting of a r and omized vaccine trial with households of size two , we use counterfactual theory under interference to provide formal definitions of a contagion effect and an unconditional infectiousness effect . Using ideas analogous to mediation analysis , we show that the indirect effect ( the effect of one person 's vaccine on another 's outcome ) can be decomposed into a contagion effect and an unconditional infectiousness effect on the risk difference , risk ratio , odds ratio , and vaccine efficacy scales . We provide identification assumptions for such contagion and unconditional infectiousness effects and describe a simple statistical technique to estimate these effects when they are identified . We also give a sensitivity analysis technique to assess how inferences would change under violations of the identification assumptions . The concepts and results of this paper are illustrated with hypothetical vaccine trial data

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Herd protection by a bivalent killed whole-cell oral cholera vaccine in the slums of Kolkata, India.

BACKGROUND We evaluated the herd protection conferred by an oral cholera vaccine using 2 approaches : cluster design and geographic information system ( GIS ) design . METHODS Residents living in 3933 dwellings ( clusters ) in Kolkata , India , were cluster-r and omized to receive either cholera vaccine or oral placebo . Nonpregnant residents aged≥1 year were invited to participate in the trial . Only the first episode of cholera detected for a subject between 14 and 1095 days after a second dose was considered . In the cluster design , indirect protection was assessed by comparing the incidence of cholera among non participants in vaccine clusters vs those in placebo clusters . In the GIS analysis , herd protection was assessed by evaluating association between vaccine coverage among the population residing within 250 m of the household and the occurrence of cholera in that population . RESULTS Among 107 347 eligible residents , 66 990 received 2 doses of either cholera vaccine or placebo . In the cluster design , the 3-year data showed significant total protection ( 66 % protection , 95 % confidence interval [ CI ] , 50%-78 % , P<.01 ) but no evidence of indirect protection . With the GIS approach , the risk of cholera among placebo recipients was inversely related to neighborhood-level vaccine coverage , and the trend was highly significant ( P<.01 ) . This relationship held in multivariable models that also controlled for potentially confounding demographic variables ( hazard ratio , 0.94 [ 95 % CI , .90-.98 ] ; P<.01 ) . CONCLUSIONS Indirect protection was evident in analyses using the GIS approach but not the cluster design approach , likely owing to considerable transmission of cholera between clusters , which would vitiate herd protection in the cluster analyses . CLINICAL TRIALS REGISTRATION NCT00289224

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Community-wide effects of permethrin-treated bed nets on child mortality and malaria morbidity in western Kenya.

Spatial analyses of the effect of insecticide (permethrin)-treated bed nets ( ITNs ) on nearby households both with and without ITNs was performed in the context of a large-scale , group-r and omized , controlled mortality trial in Asembo , western Kenya . Results illustrate a protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality , moderate anemia , high-density parasitemia , and hemoglobin levels . This community effect on nearby compounds without nets is approximately as strong as the effect observed within villages with ITNs . This implies that in areas with intense malaria transmission with high ITN coverage , the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not , as commonly supposed , by simple imposition of a physical barrier protecting individuals from biting . The strength of the community effect depended upon the proportion of nearby compounds with treated nets . To maximize their public health impact , high coverage with treated nets is essential

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Improving immunisation coverage in rural India: clustered randomised controlled evaluation of immunisation campaigns with and without incentives

Objective To assess the efficacy of modest non-financial incentives on immunisation rates in children aged 1 - 3 and to compare it with the effect of only improving the reliability of the supply of services . Design Clustered r and omised controlled study . Setting Rural Rajasthan , India . Participants 1640 children aged 1 - 3 at end point . Interventions 134 villages were r and omised to one of three groups : a once monthly reliable immunisation camp ( intervention A ; 379 children from 30 villages ) ; a once monthly reliable immunisation camp with small incentives ( raw lentils and metal plates for completed immunisation ; intervention B ; 382 children from 30 villages ) , or control ( no intervention , 860 children in 74 villages ) . Surveys were undertaken in r and omly selected households at baseline and about 18 months after the interventions started ( end point ) . Main outcome measures Proportion of children aged 1 - 3 at the end point who were partially or fully immunised . Results Among children aged 1 - 3 in the end point survey , rates of full immunisation were 39 % ( 148/382 , 95 % confidence interval 30 % to 47 % ) for intervention B villages ( reliable immunisation with incentives ) , 18 % ( 68/379 , 11 % to 23 % ) for intervention A villages ( reliable immunisation without incentives ) , and 6 % ( 50/860 , 3 % to 9 % ) for control villages . The relative risk of complete immunisation for intervention B versus control was 6.7 ( 4.5 to 8.8 ) and for intervention B versus intervention A was 2.2 ( 1.5 to 2.8 ) . Children in areas neighbouring intervention B villages were also more likely to be fully immunised than those from areas neighbouring intervention A villages ( 1.9 , 1.1 to 2.8 ) . The average cost per immunisation was $ 28 ( 1102 rupees , about £ 16 or € 19 ) in intervention A and $ 56 ( 2202 rupees ) in intervention B. Conclusions Improving reliability of services improves immunisation rates , but the effect remains modest . Small incentives have large positive impacts on the uptake of immunisation services in re source poor areas and are more cost effective than purely improving supply . Trial registration IRSCTN87759937

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Effect of scaling up women's groups on birth outcomes in three rural districts in Bangladesh: a cluster-randomised controlled trial

BACKGROUND Two recent trials have shown that women 's groups can reduce neonatal mortality in poor communities . We assessed the effectiveness of a scaled-up development programme with women 's groups to address maternal and neonatal care in three rural districts of Bangladesh . METHODS 18 clusters ( with a mean population of 27 953 [ SD 5953 ] ) in three districts were r and omly assigned to either intervention or control ( nine clusters each ) by use of stratified r and omisation . For each district , cluster names were written on pieces of paper , which were folded and placed in a bottle . The first three cluster names drawn from the bottle were allocated to the intervention group and the remaining three to control . All clusters received health services strengthening and basic training of traditional birth attendants . In intervention clusters , a facilitator convened 18 groups every month to support participatory action and learning for women , and to develop and implement strategies to address maternal and neonatal health problems . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study period ( Feb 1 , 2005 , to Dec 31 , 2007 ) . Neither study investigators nor participants were masked to treatment assignment . In a population of 229 195 people ( intervention clusters only ) , 162 women 's groups provided coverage of one group per 1414 population . The primary outcome was neonatal mortality rate ( NMR ) . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N54792066 . FINDINGS We monitored outcomes for 36 113 births ( intervention clusters , n=17 514 ; control clusters , n=18 599 ) in a population of 503 163 over 3 years . From 2005 to 2007 , there were 570 neonatal deaths in the intervention clusters and 656 in the control clusters . Cluster-level mean NMR ( adjusted for stratification and clustering ) was 33.9 deaths per 1000 livebirths in the intervention clusters compared with 36.5 per 1000 in the control clusters ( risk ratio 0.93 , 95 % CI 0.80 - 1.09 ) . INTERPRETATION For participatory women 's groups to have a significant effect on neonatal mortality in rural Bangladesh , detailed attention to programme design and context ual factors , enhanced population coverage , and increased enrolment of newly pregnant women might be needed . FUNDING Women and Children First , the UK Big Lottery Fund , Saving Newborn Lives , and the UK Department for International Development

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Impact of pediatric vaccination with pneumococcal conjugate vaccine on the risk of bacteremic pneumococcal pneumonia in adults.

Invasive pneumococcal disease in adults may be declining , reflecting a form of herd protection from a new pediatric pneumococcal conjugate vaccine . Our aim was to determine whether vaccination of children protects adults in the same home from bacteremic pneumococcal pneumonia . We conducted a case-control study with 43 participating hospitals across a five-county region in Pennsylvania . Eligible cases were adults with bacteremic pneumococcal pneumonia identified by the microbiology laboratories at participating hospitals . Controls were healthy adults from the region identified through r and om digit dialing . Cases and controls were interviewed by telephone . We analyzed vaccine protection in those adults who reported living in homes with at least one child < or = 6 years of age . From April 2002 through June 2004 , there was a significant decline in the proportion of adult pneumococcal bacteremia due to any of the seven serotypes in the conjugate vaccine ( p=0.006 ) . Within this time period , 17 % of cases and controls reported living in homes with at least one child < or = 6 years of age . In adjusted analysis , vaccination of the youngest child in the home was associated with an 80 % reduction in the odds of bacteremic pneumococcal pneumonia among adults with children in the home ( OR=0.2 , 95 % CI 0.1 - 0.8 ) . We conclude that introduction of a pneumococcal conjugate vaccine for children has reduced the population rate of adult pneumococcal bacteremia due to vaccine serotypes and is associated with a reduced risk of bacteremic pneumococcal pneumonia for adults with children in the home

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Relationship between neighbourhood-level killed oral cholera vaccine coverage and protective efficacy: evidence for herd immunity.

OBJECTIVES The effectiveness of vaccines in population s must consider both direct and indirect protection . This study reanalyses data from a large individually r and omized oral cholera vaccine trial that was conducted in rural Bangladesh from 1985 to 1990 . A recent analysis of the results of that trial showed that the proportion of people in household clusters who received the vaccine was inversely related to placebo incidence during the first year of surveillance , which was attributed to herd immunity . METHODS In this study we measure the relationship between neighbourhood-level oral cholera vaccine coverage and protective efficacy ( PE ) during a 2 year follow-up period , controlling for known effect modifiers . We link trial data to a household geographic information system to facilitate the neighbourhood-level analysis . Findings Neighbourhood-level PE can be partially explained by vaccine coverage after adjusting for ecological variables . CONCLUSIONS The inverse relationship between vaccine coverage and efficacy illustrates that people living in high-coverage areas may be indirectly protected from cholera because people living around them are vaccinated

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

The association between latrine use and trachoma: a secondary cohort analysis from a randomized clinical trial.

Latrine use has been promoted as a component of an integrated strategy for trachoma control . As part of a r and omized trial in Ethiopia , 12 communities received a mass azithromycin distribution followed by a latrine promotion intervention . A r and om sample of children ages 0 - 9 years in each community was monitored longitudinally for ocular chlamydia . After latrine construction ended , those communities with a higher proportion of households using latrines were more likely to experience a reduction in the prevalence of ocular chlamydia . Specifically , for each 10 % increase in latrine use , there was a 2.0 % decrease ( 95 % confidence interval = 0.2 - 3.9 % decrease ) in the community prevalence of ocular chlamydia over the subsequent year ( P = 0.04 )

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Effectiveness and spillover of an after-school health promotion program for Hispanic elementary school children.

OBJECTIVES We evaluated the effectiveness and spillover of an after-school health education and physical activity program among Hispanic elementary school children . METHODS In fall 2008 , students in third through fifth grade s in 6 schools in El Paso , Texas ( n = 901 ) , were r and omized to intervention ( n = 292 participants ) or control ( n = 354 ) classrooms ( 4 unknown ) . Intervention classrooms also contained a spillover group ( n = 251 ) that did not join the after-school program but that completed measurements and surveys . The intervention was a 12-week culturally tailored after-school program meeting twice a week . Four-month outcomes were body mass index , aerobic capacity , and dietary intentions and knowledge . We calculated intervention exposure as the proportion of after-school participants per classroom . RESULTS Intervention exposure predicted lower body mass index ( P = .045 ) , higher aerobic capacity ( P = .012 ) , and greater intentions to eat healthy ( P = .046 ) for the classroom at follow-up . Intervention effectiveness increased with increasing proportions of intervention participants in a classroom . Non participants who had classroom contact with program participants experienced health improvements that could reduce their risk of obesity . CONCLUSIONS Spillover of beneficial intervention effects to non participants is a valuable public health benefit and should be part of program impact assessment

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Effectiveness of an oral cholera vaccine in Zanzibar: findings from a mass vaccination campaign and observational cohort study.

BACKGROUND Zanzibar , in east Africa , has been severely and repeatedly affected by cholera since 1978 . We assessed the effectiveness of oral cholera vaccination in high-risk population s in the archipelago to estimate the indirect ( herd ) protection conferred by the vaccine and direct vaccine effectiveness . METHODS We offered two doses of a killed whole-cell B-subunit cholera vaccine to individuals aged 2 years and older in six rural and urban sites . To estimate vaccine direct protection , we compared the incidence of cholera between recipients and non-recipients using generalised estimating equations with the log link function while controlling for potential confounding variables . To estimate indirect effects , we used a geographic information systems approach and assessed the association between neighbourhood-level vaccine coverage and the risk for cholera in the non-vaccinated residents of that neighbourhood , after controlling for potential confounding variables . This study is registered with Clinical Trials.gov , number NCT00709410 . FINDINGS Of 48,178 individuals eligible to receive the vaccine , 23,921 ( 50 % ) received two doses . Between February , 2009 , and May , 2010 , there was an outbreak of cholera , enabling us to assess vaccine effectiveness . The vaccine conferred 79 % ( 95 % CI 47 - 92 ) direct protection against cholera in participants who received two doses . Indirect ( herd ) protection was shown by a decrease in the risk for cholera of non-vaccinated residents within a household 's neighbourhood as the vaccine coverage in that neighbourhood increased . INTERPRETATION Our findings suggest that the oral cholera vaccine offers both direct and indirect ( herd ) protection in a sub-Saharan African setting . Mass oral cholera immunisation campaigns have the potential to provide not only protection for vaccinated individuals but also for the unvaccinated members of the community and should be strongly considered for wider use . Because this is an internationally-licensed vaccine , we could not undertake a r and omised placebo-controlled trial , but the absence of vaccine effectiveness against non-cholera diarrhoea indicates that the noted protection against cholera could not be explained by bias . FUNDING Bill & Melinda Gates Foundation , Swedish International Development Cooperation Agency , and the South Korean Government

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Toward Causal Inference With Interference

A fundamental assumption usually made in causal inference is that of no interference between individuals ( or units ) ; that is , the potential outcomes of one individual are assumed to be unaffected by the treatment assignment of other individuals . However , in many setting s , this assumption obviously does not hold . For example , in the dependent happenings of infectious diseases , whether one person becomes infected depends on who else in the population is vaccinated . In this article , we consider a population of groups of individuals where interference is possible between individuals within the same group . We propose estim and s for direct , indirect , total , and overall causal effects of treatment strategies in this setting . Relations among the estim and s are established ; for example , the total causal effect is shown to equal the sum of direct and indirect causal effects . Using an experimental design with a two-stage r and omization procedure ( first at the group level , then at the individual level within groups ) , unbiased estimators of the proposed estim and s are presented . Variances of the estimators are also developed . The methodology is illustrated in two different setting s where interference is likely : assessing causal effects of housing vouchers and of vaccines

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Effectiveness of Vi capsular polysaccharide typhoid vaccine among children: a cluster randomized trial in Karachi, Pakistan.

BACKGROUND Typhoid fever is endemic in Karachi , with an incidence among children ranging from 170 to 450 per 100,000 child-years . Vaccination strategies are important for prevention , and the Vi capsular polysaccharide ( ViCPS ) vaccine has been shown to be effective in reducing the burden of typhoid fever . METHODS A cluster r and omized trial was conducted in three low socioeconomic urban squatter settlements in Karachi , Pakistan between 2002 and 2007 . Sub sample s were followed up for assessment of immune response and adverse events after vaccination . RESULTS The study participants were similar in a wide variety of socio-demographic and economic characteristics at baseline . A total of 27,231 individuals of the total target population of 51,965 in 120 clusters either received a ViCPS vaccine ( 13,238 [ 52 % coverage ] ) or the control Hepatitis A vaccine ( 13,993 [ 53 % ] ) . Typhoid fever was diagnosed in 30 ViCPS vaccine recipients and 49 Hepatitis A vaccine recipients with an adjusted total protective effectiveness of 31 % ( 95%CI : -28 % , 63 % ) . The adjusted total vaccine protective effectiveness was -38 % ( 95%CI : -192 % , 35 % ) for children aged 2 - 5 years and 57 % ( 95%CI : 6 % , 81 % ) for children 5 - 16 years old . CONCLUSION The ViCPS vaccine did not confer statistically significant protection to children in the study areas , and there was a decline in antibody response 2 years post-vaccination . However , the ViCPS vaccine showed significant total protection in children 5 - 16 years of age , which is consistent with other studies of ViCPS vaccine conducted in India , Nepal , China and South Africa . These findings suggest that ViCPS vaccination of school-aged children will protect the children of urban , typhoid endemic areas against typhoid fever

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Herd immunity in adults against influenza-related illnesses with use of the trivalent-live attenuated influenza vaccine (CAIV-T) in children.

Highest attack rates for influenza occur in children . Immunization of schoolchildren with inactivated influenza vaccine in Michigan and Japan was associated with decreased morbidity and mortality , respectively , in older community contacts . An open-labeled , non-r and omized , community-based trial in children with the cold adapted influenza vaccine , trivalent ( CAIV-T ) was initiated to determine the coverage necessary to reduce spread of influenza in the community . Age-specific baseline rates of medically attended acute respiratory illness ( MAARI ) for Scott and White Health Plan ( SWHP ) members at intervention ( Temple and Belton ) and comparison communities ( Waco , Bryan , and College Station ) were obtained in 1997 - 1998 . During three subsequent vaccination years , 4298 , 5251 and 5150 children received one dose per season of CAIV-T. Vaccinees represented 20 - 25 % of the age-eligible children . Age-specific MAARI rates were compared for SWHP members in the intervention and comparison sites during the influenza outbreaks . Baseline age-specific MAARI rates per 100 persons for the influenza season were comparable between the intervention and comparison communities . In the subsequent three influenza seasons , the age groups 35 - 44 , 45 - 54 , 55 - 65 and > 64 years experienced reductions in MAARI rates in the intervention communities . In adults > or = 35 years of age , significant reductions in MAARI of 0.08 ( 95 % CI : 0.04 , 0.13 ) , 0.18 ( 95 % CI : 0.14 , 0.22 ) and 0.15 ( 95 % CI : 0.12 , 0.19 ) , were observed in the influenza seasons for vaccination years 1 , 2 and 3 , respectively . No consistent reduction in MAARI rates was detected in the younger age groups . Vaccination of approximately 20 - 25 % of children , 1.5 - 18 years of age in the intervention communities result ed in an indirect protection of 8 - 18 % against MAARI in adults > or = 35 years of age

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Peer effects in learning HIV results.

How do neighbors positively or negatively influence individuals living in rural Malawi to learn their HIV results ? Using data of location of homes and distance to neighbors , we measure the social network effects of neighbors ' learning their HIV results on individuals own learning . Using the fact that neighbors were r and omly offered monetary incentives of varying amounts to learn their HIV results , we find positive effects of neighbors attending clinics on others living nearby : a 10 percentage point increase of the percentage of neighbors ( approximately 2.4 individuals ) learning their HIV results increases the probability of learning HIV results by 1.1 percentage points . The strongest network effects are among closest neighbors ; we find no effect among religious social networks . We also find a negative interaction between direct cash incentives and peers : the effect of peers doubles among those who were not offered any individual financial incentive to learn their HIV results

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Distance to health services affects local-level vaccine efficacy for pneumococcal conjugate vaccine (PCV) among rural Filipino children

Significance Although pneumococcal conjugate vaccines ( PCVs ) are widely available in industrialized nations , the cost of these vaccines and the strategy of universal vaccination of infants , as endorsed by the World Health Organization , are daunting obstacles to the adoption of these vaccines in developing countries . Using spatial epidemiological methods to examine the spatial variation in vaccine efficacy ( VE ) in an 11-valent PCV trial in Bohol , Philippines , we suggest an alternative strategy to universal vaccination . Our main finding suggests that areas with poor access to healthcare have the highest VE . An alternative vaccination strategy could target vaccination to areas where children are most likely to benefit , rather than focus on nationwide immunization . Pneumococcal conjugate vaccines ( PCVs ) have demonstrated efficacy against childhood pneumococcal disease in several regions globally . We demonstrate how spatial epidemiological analysis of a PCV trial can assist in developing vaccination strategies that target specific geographic sub population s at greater risk for pneumococcal pneumonia . We conducted a secondary analysis of a r and omized , placebo-controlled , double-blind vaccine trial that examined the efficacy of an 11-valent PCV among children less than 2 y of age in Bohol , Philippines . Trial data were linked to the residential location of each participant using a geographic information system . We use spatial interpolation methods to create smoothed surface maps of vaccination rates and local-level vaccine efficacy across the study area . We then measure the relationship between distance to the main study hospital and local-level vaccine efficacy , controlling for ecological factors , using spatial autoregressive models with spatial autoregressive disturbances . We find a significant amount of spatial variation in vaccination rates across the study area . For the primary study endpoint vaccine efficacy increased with distance from the main study hospital from −14 % for children living less than 1.5 km from Bohol Regional Hospital ( BRH ) to 55 % for children living greater than 8.5 km from BRH . Spatial regression models indicated that after adjustment for ecological factors , distance to the main study hospital was positively related to vaccine efficacy , increasing at a rate of 4.5 % per kilometer distance . Because areas with poor access to care have significantly higher VE , targeted vaccination of children in these areas might allow for a more effective implementation of global programs

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Assessing effects of cholera vaccination in the presence of interference.

Interference occurs when the treatment of one person affects the outcome of another . For example , in infectious diseases , whether one individual is vaccinated may affect whether another individual becomes infected or develops disease . Quantifying such indirect ( or spillover ) effects of vaccination could have important public health or policy implication s. In this article we use recently developed inverse-probability weighted ( IPW ) estimators of treatment effects in the presence of interference to analyze an individually-r and omized , placebo-controlled trial of cholera vaccination that targeted 121,982 individuals in Matlab , Bangladesh . Because these IPW estimators have not been employed previously , a simulation study was also conducted to assess the empirical behavior of the estimators in setting s similar to the cholera vaccine trial . Simulation study results demonstrate the IPW estimators can yield unbiased estimates of the direct , indirect , total , and overall effects of vaccination when there is interference provided the untestable no unmeasured confounders assumption holds and the group-level propensity score model is correctly specified . Application of the IPW estimators to the cholera vaccine trial indicates the presence of interference . For example , the IPW estimates suggest on average 5.29 fewer cases of cholera per 1000 person-years ( 95 % confidence interval 2.61 , 7.96 ) will occur among unvaccinated individuals within neighborhoods with 60 % vaccine coverage compared to neighborhoods with 32 % coverage . Our analysis also demonstrates how not accounting for interference can render misleading conclusions about the public health utility of vaccination

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .

Users identified challenges in applying GRADE to complex interventions and suggested an extension to GRADE.

OBJECTIVES To explore user perspectives on applying the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) to systematic review s of complex interventions . STUDY DESIGN AND SETTING Thirty-three authors of recent ( 2013 onward ) systematic review s were contacted regarding their perspectives on using GRADE from three Cochrane review groups : Cochrane Developmental , Psychosocial , and Learning Problems Group ; Cochrane Public Health Group ; and Cochrane Depression , Anxiety , and Neurosis Group . Framework Analysis was applied to the data to identify the challenges in applying GRADE and suggestions for its extension , that is , adaptation . These two themes were cross-compared between the groups of answers from " simple " vs. " complex " intervention review authors to identify the specific perspectives on using GRADE in review s of complex interventions . RESULTS Specific challenges were identified in applying GRADE to review s of complex interventions . These were related to the assessment of nonr and omized studies and performance bias in GRADE . Authors perceived these challenges to contribute to frequent downgrading of the " best evidence possible " for complex interventions . Meanwhile , GRADE was found to lack an analytic approach to enable adequate evidence synthesis and assessment of intervention implementation elements . CONCLUSION Users suggest that the GRADE guidance be extended to address-specific considerations for complex interventions

We identified three primary mechanisms of spillovers : reduced disease transmission , social proximity and substitution of re sources within households . We found the strongest evidence for spillovers through reduced disease transmission , particularly vaccines and mass drug administration . In general , the proportion of a population receiving an intervention was associated with improved health . We found evidence of publication bias for certain spillover estimates but not for total or direct effects . Conclusions We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease . There was little high quality evidence of spillovers for other interventions

Background Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity . Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects .