human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract Twenty-four volunteers ( 19 women and five men ) with insomnia and a history of chronic use of benzodiazepine hypnotics  participated in a r and omized , double blind , controlled clinical trial . The study was design ed to assess the effects of substituting zopiclone ( ZOP ) – as an hypnotic – among chronic users of flunitrazepam ( FLU )  , and to compare the subsequent withdrawal of ZOP with placebo controlled withdrawal of FLU . During the 5 weeks of a withdrawal protocol , sleep and physiological parameters were assessed by polysomnographic measures for 11 nights and by nightly actigraphic recordings for weeks 1 , 3 , and 5 . Subjective effects of the withdrawal process were evaluated with daily sleep diaries , and with various weekly self-report symptom checklists . Paired t-tests performed on differences in objective sleep parameters between baseline and the last weeks of the withdrawal program showed a significant decrease in sleep quality within the FLU group , but not in the ZOP group . Subjective sleep diaries consistently reflected the objective ly measured changes in sleep throughout the withdrawal program , indicating significant changes in sleep parameters only in the FLU group . The results obtained from the self report inventories aim ed at assessing withdrawal symptoms , however , revealed no differences between the baseline week and the termination week of the program in any of the groups . After completing the pharmacological withdrawal , all subjects received a short-term cognitive behavioral intervention focused on improving their coping strategies with symptoms of insomnia ; they were evaluated immediately after concluding the intervention , and at 3 and 12 month follow-ups Eighty-six participants wishing to stop benzodiazepine and who met DSM-IV ( Diagnostic and Statistical Manual of Mental Disorders , 4th ed . American Psychological Association , 1994 ) criteria for anxiety disorder or insomnia were assessed pre- and post-taper on clinical , pharmacological and psychosocial measures . An initial cohort of 41 participants received treatment as usual ( taper only ) plus physician counselling in the same clinic setting . A second cohort of 45 participants were r and omly allocated to group cognitive-behavioural therapy ( CBT ) plus taper , or group support ( GS ) plus taper . At 3 months follow-up , the outcomes in both the CBT and the GS subgroups were equivalent . Intention to treat analysis revealed a slight advantage to the CBT over the GS group and the CBT group showed higher self-efficacy post-taper . Over all 86 participants , a high-baseline level of psychological distress , anxiety and dosage predicted a poor outcome , but increase in self-efficacy contributed to a successful outcome particularly in those with initially poor baseline predictors . Although there was a decrease in positive affect during preliminary stages of tapered discontinuation compared to baseline , there was no significant overall increase in negative affect BACKGROUND Benzodiazepines are extensively used in primary care , but their long-term use is associated with adverse health outcomes and dependence . AIMS To analyse the efficacy of two structured interventions in primary care to enable patients to discontinue long-term benzodiazepine use . METHOD A multicentre three-arm cluster r and omised controlled trial was conducted , with r and omisation at general practitioner level ( trial registration IS RCT N13024375 ) . A total of 532 patients taking benzodiazepines for at least 6 months participated . After all patients were included , general practitioners were r and omly allocated ( 1:1:1 ) to usual care , a structured intervention with follow-up visits ( SIF ) or a structured intervention with written instructions ( SIW ) . The primary end-point was the last month self-declared benzodiazepine discontinuation confirmed by prescription cl aims at 12 months . RESULTS At 12 months , 76 of 168 ( 45 % ) patients in the SIW group and 86 of 191 ( 45 % ) in the SIF group had discontinued benzodiazepine use compared with 26 of 173 ( 15 % ) in the control group . After adjusting by cluster , the relative risks for benzodiazepine discontinuation were 3.01 ( 95 % CI 2.03 - 4.46 , P<0.0001 ) in the SIW and 3.00 ( 95 % CI 2.04 - 4.40 , P<0.0001 ) in the SIF group . The most frequently reported withdrawal symptoms were insomnia , anxiety and irritability . CONCLUSIONS Both interventions led to significant reductions in long-term benzodiazepine use in patients without severe comorbidity . A structured intervention with a written individualised stepped-dose reduction is less time-consuming and as effective in primary care as a more complex intervention involving follow-up visits Withdrawal from hypnotics can produce a variety of problems , especially sleep difficulties , some of which may arise from the multiple actions of most hypnotics , thus producing a range of rebound effects . This study examined whether switching patients to a hypnotic with a narrower range of action and of a different class would reduce these problems . One hundred and thirty-four patients participated ; they were r and omly allocated to one of three methods of switching from " previous hypnotic " to zopiclone ( a cyclopyrrolone ) . The methods were gap ( an interval between taking the two drugs ) ; abuttal ( taking zopiclone immediately on stopping previous drug ) ; and overlap ( gradually reducing previous drug after starting zopiclone ) . The main findings were that zopiclone was associated with better sleep and increased alertness ; the abuttal method was the best method of switching ; and no serious side effects from zopiclone were reported . It was concluded that zopiclone has a useful role in benzodiazepine withdrawal , and that immediate substitution is the best method The Johns Hopkins Precursors Study , a long-term prospect i ve study , was used to study the relation between self-reported sleep disturbances  and subsequent clinical depression and psychiatric distress .  A total of 1,053 men provided information on sleep habits during medical school at The Johns Hopkins University ( classes of 1948 - 1964 ) and have been followed since graduation . During a median follow-up period of 34 years ( range 1 - 45 ) , 101 men developed clinical depression  ( cumulative incidence at 40 years , 12.2 % ) , including 13 suicides . In Cox proportional hazards analysis adjusted for age at graduation , class year , parental history of clinical depression , coffee drinking , and measures of temperament , the relative risk of clinical depression was greater in those who reported insomnia in medical school ( relative risk ( RR ) 2.0 , 95 % confidence interval ( CI ) 1.2 - 3.3 ) compared with those who did not and greater in those with difficulty sleeping under stress in medical school ( RR 1.8 , 95 % CI 1.2 - 2.7 ) compared with those who did not report difficulty . There were weaker associations for those who reported poor quality of sleep ( RR 1.6 , 95 % CI 0.9 - 2.9 ) and sleep duration of 7 hours or less ( RR 1.5 , 95 % CI 0.9 - 2.3 ) with development of clinical depression . Similar associations were observed between reports of sleep disturbances in medical school and psychiatric distress assessed in 1988 by the General Health Question naire . These findings suggest that insomnia in young men is indicative of a greater risk for subsequent clinical depression and psychiatric distress that persists for at least 30 years BACKGROUND Benzodiazepine withdrawal programmes have never been experimentally compared with a nonintervention control condition . AIMS To evaluate the efficacy and feasibility of tapering off long-term benzodiazepine use in general practice , and to evaluate the value of additional group cognitive-behavioural therapy ( CBT ) . METHOD A 3-month r and omised , 3-month controlled trial was conducted in which 180 people attempting to discontinue long-term benzodiazepine use were assigned to tapering off plus group CBT , tapering off alone or usual care . RESULTS Tapering off led to a significantly higher proportion of successful discontinuations than usual care ( 62 % nu . 21 % ) . Adding group CBT did not increase the success rate ( 58 % v. 62 % ) . Neither successful discontinuation nor intervention type affected psychological functioning . Both tapering strategies showed good feasibilityin general practice . CONCLUSIONS Tapering off is a feasible and effective way of discontinuing long-term benzodiazepine use in general practice . The addition of group CBT is of limited value Objective A r and omised , controlled clinical trial was performed to study the long-term effect of gradual withdrawal from benzodiazepines on the daily functioning of residents of homes for the elderly . The planned sample size was not achieved due to recruitment and follow-up problems . Results The results in this small sample nevertheless suggest that gradual withdrawal from benzodiazepines is possible in residents of homes for the elderly , and that it can have a positive effect on their daily functioning . No major withdrawal symptoms were observed , although there was a decrease in sleep quality during withdrawal . Conclusion The findings are promising for further research , but research ers should anticipate the problems inherent in executing a trial with institutionalised elderly subjects This study aim ed to assess the efficacy of a minimal intervention focusing on hypnotic discontinuation and cognitive-behavioral treatment ( CBT ) for  insomnia . Fifty-three adult chronic users of hypnotics were r and omly assigned to an 8-week hypnotic taper program , used alone or combined with a self-help CBT .  Weekly hypnotic use decreased in both conditions , from a nearly nightly use at baseline to less than once a week at posttreatment . Nightly dosage ( in lorazepam equivalent ) decreased from 1.67 mg to 0.12 mg . Participants who received CBT improved their sleep efficiency by 8 % , whereas those who did not remained stable . Total wake time decreased by 52 min among CBT participants and increased by 13 min among those receiving the taper schedule alone . Total sleep time remained stable throughout withdrawal in both CBT and taper conditions . The present findings suggest that a systematic withdrawal schedule might be sufficient in helping chronic users stop their hypnotic medication . The addition of a self-help treatment focusing on insomnia , a readily available and cost-effective alternative to individual psychotherapy , produced greater sleep improvement BACKGROUND Older adults are the main recipients of repeat prescriptions for benzodiazepine ( BZD ) hypnotics . BZDs can impair cognitive function and may not aid sleep when taken continuously for years . This study therefore aim ed to determine if withdrawing from BZDs leads to changes in patients ' cognitive function , quality of life , mood and sleep . METHOD One hundred and ninety-two long-term users of BZD hypnotics , aged > or = 65 years , were identified in 25 general practice s. One hundred and four who wished to withdraw were r and omly allocated to one of two groups under double-blind , placebo controlled conditions : group A 's BZD dose was tapered from week 1 of the trial ; group B were given their usual dose for 12 weeks and then it was tapered . An additional group ( C ) of 35 patients who did not wish to withdraw from BZDs participated as ' continuers ' . All patients were assessed at 0 , 12 and 24 weeks and 50 % were reassessed at 52 weeks . RESULTS Sixty per cent of patients had taken BZDs continuously for > 10 years ; 27 % for > 20 years . Of all patients beginning the trial , 80 % had successfully withdrawn 6 months later . There was little difference between groups A and B , but these groups differed from continuers ( C ) in that the performance of the withdrawers on several cognitive/psychomotor tasks showed relative improvements at 24 or 52 weeks . Withdrawers and continuers did not differ in sleep or BZD withdrawal symptoms . CONCLUSIONS These results have clear implication s for clinical practice . Withdrawal from BZDs produces some subtle cognitive advantages for older people , yet little in the way of withdrawal symptoms or emergent sleep difficulties . These findings also suggest that , taken long-term , BZDs do not aid sleep CONTEXT Insomnia is a major health problem with significant psychological , health , and economic consequences . However , availability of one of the most effective insomnia treatments , cognitive behavioral therapy , is significantly limited . The Internet may be a key conduit for delivering this intervention . OBJECTIVE To evaluate the efficacy of a structured behavioral Internet intervention for adults with insomnia . DESIGN , SETTING , AND PARTICIPANTS Forty-five adults were r and omly assigned to an Internet intervention  ( n = 22 ) or wait-list control group  ( n = 23 ) . Forty-four eligible participants ( mean [ SD ] age , 44.86 [ 11.03 ] years ; 34 women ) who had a history of sleep difficulties longer than 10 years on average ( mean [ SD ] , 10.59 [ 8.89 ] years ) were included in the analyses . INTERVENTION The Internet intervention is based on well-established face-to-face cognitive behavioral therapy incorporating the primary components of sleep restriction , stimulus control , sleep hygiene , cognitive restructuring , and relapse prevention . MAIN OUTCOME MEASURES The Insomnia Severity Index and daily sleep diary data were used to determine changes in insomnia severity and the main sleep variables , including wake after sleep onset and sleep efficiency . RESULTS Intention-to-treat analyses showed that scores on the Insomnia Severity Index significantly improved from 15.73 ( 95 % confidence interval [ CI ] , 14.07 to 17.39 ) to 6.59 ( 95 % CI ,  
    Output:
    
agent
This guideline does not apply to those with other sleep disorders or untreated anxiety , depression , or other physical or mental health conditions that might be causing or aggravating insomnia .
Benzodiazepine receptor agonists are associated with harms , and therapeutic effects might be short term .
Tapering BZRAs improves cessation rates compared with usual care without serious harms .
Patients might be more amenable to deprescribing conversations if they underst and the rationale ( potential for harm ) , are involved in developing the tapering plan , and are offered behavioural advice .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract Twenty-four volunteers ( 19 women and five men ) with insomnia and a history of chronic use of benzodiazepine hypnotics  participated in a r and omized , double blind , controlled clinical trial . The study was design ed to assess the effects of substituting zopiclone ( ZOP ) – as an hypnotic – among chronic users of flunitrazepam ( FLU )  , and to compare the subsequent withdrawal of ZOP with placebo controlled withdrawal of FLU . During the 5 weeks of a withdrawal protocol , sleep and physiological parameters were assessed by polysomnographic measures for 11 nights and by nightly actigraphic recordings for weeks 1 , 3 , and 5 . Subjective effects of the withdrawal process were evaluated with daily sleep diaries , and with various weekly self-report symptom checklists . Paired t-tests performed on differences in objective sleep parameters between baseline and the last weeks of the withdrawal program showed a significant decrease in sleep quality within the FLU group , but not in the ZOP group . Subjective sleep diaries consistently reflected the objective ly measured changes in sleep throughout the withdrawal program , indicating significant changes in sleep parameters only in the FLU group . The results obtained from the self report inventories aim ed at assessing withdrawal symptoms , however , revealed no differences between the baseline week and the termination week of the program in any of the groups . After completing the pharmacological withdrawal , all subjects received a short-term cognitive behavioral intervention focused on improving their coping strategies with symptoms of insomnia ; they were evaluated immediately after concluding the intervention , and at 3 and 12 month follow-ups Eighty-six participants wishing to stop benzodiazepine and who met DSM-IV ( Diagnostic and Statistical Manual of Mental Disorders , 4th ed . American Psychological Association , 1994 ) criteria for anxiety disorder or insomnia were assessed pre- and post-taper on clinical , pharmacological and psychosocial measures . An initial cohort of 41 participants received treatment as usual ( taper only ) plus physician counselling in the same clinic setting . A second cohort of 45 participants were r and omly allocated to group cognitive-behavioural therapy ( CBT ) plus taper , or group support ( GS ) plus taper . At 3 months follow-up , the outcomes in both the CBT and the GS subgroups were equivalent . Intention to treat analysis revealed a slight advantage to the CBT over the GS group and the CBT group showed higher self-efficacy post-taper . Over all 86 participants , a high-baseline level of psychological distress , anxiety and dosage predicted a poor outcome , but increase in self-efficacy contributed to a successful outcome particularly in those with initially poor baseline predictors . Although there was a decrease in positive affect during preliminary stages of tapered discontinuation compared to baseline , there was no significant overall increase in negative affect BACKGROUND Benzodiazepines are extensively used in primary care , but their long-term use is associated with adverse health outcomes and dependence . AIMS To analyse the efficacy of two structured interventions in primary care to enable patients to discontinue long-term benzodiazepine use . METHOD A multicentre three-arm cluster r and omised controlled trial was conducted , with r and omisation at general practitioner level ( trial registration IS RCT N13024375 ) . A total of 532 patients taking benzodiazepines for at least 6 months participated . After all patients were included , general practitioners were r and omly allocated ( 1:1:1 ) to usual care , a structured intervention with follow-up visits ( SIF ) or a structured intervention with written instructions ( SIW ) . The primary end-point was the last month self-declared benzodiazepine discontinuation confirmed by prescription cl aims at 12 months . RESULTS At 12 months , 76 of 168 ( 45 % ) patients in the SIW group and 86 of 191 ( 45 % ) in the SIF group had discontinued benzodiazepine use compared with 26 of 173 ( 15 % ) in the control group . After adjusting by cluster , the relative risks for benzodiazepine discontinuation were 3.01 ( 95 % CI 2.03 - 4.46 , P<0.0001 ) in the SIW and 3.00 ( 95 % CI 2.04 - 4.40 , P<0.0001 ) in the SIF group . The most frequently reported withdrawal symptoms were insomnia , anxiety and irritability . CONCLUSIONS Both interventions led to significant reductions in long-term benzodiazepine use in patients without severe comorbidity . A structured intervention with a written individualised stepped-dose reduction is less time-consuming and as effective in primary care as a more complex intervention involving follow-up visits Withdrawal from hypnotics can produce a variety of problems , especially sleep difficulties , some of which may arise from the multiple actions of most hypnotics , thus producing a range of rebound effects . This study examined whether switching patients to a hypnotic with a narrower range of action and of a different class would reduce these problems . One hundred and thirty-four patients participated ; they were r and omly allocated to one of three methods of switching from " previous hypnotic " to zopiclone ( a cyclopyrrolone ) . The methods were gap ( an interval between taking the two drugs ) ; abuttal ( taking zopiclone immediately on stopping previous drug ) ; and overlap ( gradually reducing previous drug after starting zopiclone ) . The main findings were that zopiclone was associated with better sleep and increased alertness ; the abuttal method was the best method of switching ; and no serious side effects from zopiclone were reported . It was concluded that zopiclone has a useful role in benzodiazepine withdrawal , and that immediate substitution is the best method The Johns Hopkins Precursors Study , a long-term prospect i ve study , was used to study the relation between self-reported sleep disturbances  and subsequent clinical depression and psychiatric distress .  A total of 1,053 men provided information on sleep habits during medical school at The Johns Hopkins University ( classes of 1948 - 1964 ) and have been followed since graduation . During a median follow-up period of 34 years ( range 1 - 45 ) , 101 men developed clinical depression  ( cumulative incidence at 40 years , 12.2 % ) , including 13 suicides . In Cox proportional hazards analysis adjusted for age at graduation , class year , parental history of clinical depression , coffee drinking , and measures of temperament , the relative risk of clinical depression was greater in those who reported insomnia in medical school ( relative risk ( RR ) 2.0 , 95 % confidence interval ( CI ) 1.2 - 3.3 ) compared with those who did not and greater in those with difficulty sleeping under stress in medical school ( RR 1.8 , 95 % CI 1.2 - 2.7 ) compared with those who did not report difficulty . There were weaker associations for those who reported poor quality of sleep ( RR 1.6 , 95 % CI 0.9 - 2.9 ) and sleep duration of 7 hours or less ( RR 1.5 , 95 % CI 0.9 - 2.3 ) with development of clinical depression . Similar associations were observed between reports of sleep disturbances in medical school and psychiatric distress assessed in 1988 by the General Health Question naire . These findings suggest that insomnia in young men is indicative of a greater risk for subsequent clinical depression and psychiatric distress that persists for at least 30 years BACKGROUND Benzodiazepine withdrawal programmes have never been experimentally compared with a nonintervention control condition . AIMS To evaluate the efficacy and feasibility of tapering off long-term benzodiazepine use in general practice , and to evaluate the value of additional group cognitive-behavioural therapy ( CBT ) . METHOD A 3-month r and omised , 3-month controlled trial was conducted in which 180 people attempting to discontinue long-term benzodiazepine use were assigned to tapering off plus group CBT , tapering off alone or usual care . RESULTS Tapering off led to a significantly higher proportion of successful discontinuations than usual care ( 62 % nu . 21 % ) . Adding group CBT did not increase the success rate ( 58 % v. 62 % ) . Neither successful discontinuation nor intervention type affected psychological functioning . Both tapering strategies showed good feasibilityin general practice . CONCLUSIONS Tapering off is a feasible and effective way of discontinuing long-term benzodiazepine use in general practice . The addition of group CBT is of limited value Objective A r and omised , controlled clinical trial was performed to study the long-term effect of gradual withdrawal from benzodiazepines on the daily functioning of residents of homes for the elderly . The planned sample size was not achieved due to recruitment and follow-up problems . Results The results in this small sample nevertheless suggest that gradual withdrawal from benzodiazepines is possible in residents of homes for the elderly , and that it can have a positive effect on their daily functioning . No major withdrawal symptoms were observed , although there was a decrease in sleep quality during withdrawal . Conclusion The findings are promising for further research , but research ers should anticipate the problems inherent in executing a trial with institutionalised elderly subjects This study aim ed to assess the efficacy of a minimal intervention focusing on hypnotic discontinuation and cognitive-behavioral treatment ( CBT ) for  insomnia . Fifty-three adult chronic users of hypnotics were r and omly assigned to an 8-week hypnotic taper program , used alone or combined with a self-help CBT .  Weekly hypnotic use decreased in both conditions , from a nearly nightly use at baseline to less than once a week at posttreatment . Nightly dosage ( in lorazepam equivalent ) decreased from 1.67 mg to 0.12 mg . Participants who received CBT improved their sleep efficiency by 8 % , whereas those who did not remained stable . Total wake time decreased by 52 min among CBT participants and increased by 13 min among those receiving the taper schedule alone . Total sleep time remained stable throughout withdrawal in both CBT and taper conditions . The present findings suggest that a systematic withdrawal schedule might be sufficient in helping chronic users stop their hypnotic medication . The addition of a self-help treatment focusing on insomnia , a readily available and cost-effective alternative to individual psychotherapy , produced greater sleep improvement BACKGROUND Older adults are the main recipients of repeat prescriptions for benzodiazepine ( BZD ) hypnotics . BZDs can impair cognitive function and may not aid sleep when taken continuously for years . This study therefore aim ed to determine if withdrawing from BZDs leads to changes in patients ' cognitive function , quality of life , mood and sleep . METHOD One hundred and ninety-two long-term users of BZD hypnotics , aged > or = 65 years , were identified in 25 general practice s. One hundred and four who wished to withdraw were r and omly allocated to one of two groups under double-blind , placebo controlled conditions : group A 's BZD dose was tapered from week 1 of the trial ; group B were given their usual dose for 12 weeks and then it was tapered . An additional group ( C ) of 35 patients who did not wish to withdraw from BZDs participated as ' continuers ' . All patients were assessed at 0 , 12 and 24 weeks and 50 % were reassessed at 52 weeks . RESULTS Sixty per cent of patients had taken BZDs continuously for > 10 years ; 27 % for > 20 years . Of all patients beginning the trial , 80 % had successfully withdrawn 6 months later . There was little difference between groups A and B , but these groups differed from continuers ( C ) in that the performance of the withdrawers on several cognitive/psychomotor tasks showed relative improvements at 24 or 52 weeks . Withdrawers and continuers did not differ in sleep or BZD withdrawal symptoms . CONCLUSIONS These results have clear implication s for clinical practice . Withdrawal from BZDs produces some subtle cognitive advantages for older people , yet little in the way of withdrawal symptoms or emergent sleep difficulties . These findings also suggest that , taken long-term , BZDs do not aid sleep CONTEXT Insomnia is a major health problem with significant psychological , health , and economic consequences . However , availability of one of the most effective insomnia treatments , cognitive behavioral therapy , is significantly limited . The Internet may be a key conduit for delivering this intervention . OBJECTIVE To evaluate the efficacy of a structured behavioral Internet intervention for adults with insomnia . DESIGN , SETTING , AND PARTICIPANTS Forty-five adults were r and omly assigned to an Internet intervention  ( n = 22 ) or wait-list control group  ( n = 23 ) . Forty-four eligible participants ( mean [ SD ] age , 44.86 [ 11.03 ] years ; 34 women ) who had a history of sleep difficulties longer than 10 years on average ( mean [ SD ] , 10.59 [ 8.89 ] years ) were included in the analyses . INTERVENTION The Internet intervention is based on well-established face-to-face cognitive behavioral therapy incorporating the primary components of sleep restriction , stimulus control , sleep hygiene , cognitive restructuring , and relapse prevention . MAIN OUTCOME MEASURES The Insomnia Severity Index and daily sleep diary data were used to determine changes in insomnia severity and the main sleep variables , including wake after sleep onset and sleep efficiency . RESULTS Intention-to-treat analyses showed that scores on the Insomnia Severity Index significantly improved from 15.73 ( 95 % confidence interval [ CI ] , 14.07 to 17.39 ) to 6.59 ( 95 % CI ,  
    Output:
    