***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: This study a ) compared the effects of buprenorphine versus methadone maintenance on benzodiazepine and alcohol use and b ) evaluated the prognostic significance of gender and psychopathology and their interaction with maintenance treatment . Eighty male and 36 female patients were r and omly assigned to daily sublingual buprenorphine ( 4 or 12 mg ) or oral methadone ( 20 or 65 mg ) . Maintenance medication was not associated with significant differences in alcohol or benzodiazepine use . Rates of abstinence from illicit opioids were significantly higher for females , within the buprenorphine 4-mg group , females also had significantly better retention , lower rates of opioid-positive urine sample s , and higher rates of abstinence from illicit opioids . Lifetime sedative dependence was associated with significantly better retention , decreased rates of cocaine-positive urine sample s , and increased rates of cocaine abstinence ; among buprenorphine- but not methadone-maintained patients , it was also associated with increased rates of abstinence from illicit opioids Sixty subjects participated in a double-blind study comparing methadyl acetate ( 80 mg ) with two dosages of methadone ( 50 mg and 100 mg ) in the maintenance of opiate addicts . The safety of all three regimens was supported and methadyl acetate was as effective as methadone in the retention of subjects It is estimated that more than 500 000 people in the United States are dependent on opioids [ 1 , 2 ] . Methadone , a synthetic opioid first reported as a treatment agent for opioid dependence by Dole and Nysw and er in 1965 [ 3 ] , is the most widely used pharmacologic treatment for opioid dependence . The National Drug and Alcoholism Treatment Unit Survey ( NDATUS ) determined a point prevalence of 92 715 opioid abusers treated in 758 methadone treatment programs on 30 September 1989 [ 4 ] . When used in conjunction with counseling services , methadone treatment has been associated with reduced rates of criminal activity , illicit drug use , and needle sharing and with improved rates of employment [ 5 - 9 ] . With the recognition of intravenous drug use as a primary risk factor for infection with human immunodeficiency virus ( HIV ) , improved access to methadone treatment has been identified as an important means for reducing the risk of HIV infection [ 10 , 11 ] . Although methadone treatment is effective in decreasing opioid use , recent studies have reported considerable variability across clinics in rates of continued intravenous drug use during treatment [ 12 ] . One aspect of this problem is that intravenous use of cocaine has become a serious problem among  methadone treatment patients [ 13 - 16 ] . Few systematic studies have addressed the efficacy of  methadone treatment since the onset of the cocaine epidemic [ 17 ] . Such research could re-evaluate in a contemporary population sample methadone 's specific pharmacologic efficacy in decreasing opioid use [ 18 - 20 ] while providing new information about any potential effect of methadone treatment on concurrent cocaine use . The issue of appropriate methadone dosing levels is highly pertinent because low-dose treatment has been strongly associated with poor drug use outcomes in descriptive clinical studies [ 12 , 21 ] and because a substantial number of clinics continue to use low doses of methadone [ 22 ] . For example , a report prepared by the General Accounting Office ( GAO ) that summarized the dosing practice s of 24 methadone programs in eight states found that doses ranged widely ( from 21 to 68 mg ) and 29 % had a mean dose of less than 40 mg [ 23 ] . Thus , despite more than 25 years of clinical experience , optimal dosing levels of methadone remain controversial [ 24 , 25 ] . Previous studies of methadone dosing have either surveyed clinics for their dosing practice and related doses to clinic-wide outcomes or have r and omly assigned patients to a specific predetermined dose of methadone using clinical trial methods . Naturalistic survey studies [ 5 , 6 , 12 , 21 , 26 ] , although valuable for identifying associations between dose and outcome , are method ologically compromised by confounding factors that differ across the clinics surveyed . Previous early clinical trials of methadone dosing [ 27 - 29 ] are also method ologically compromised ( for example , being single-blinded ) or only tested higher doses of methadone [ 30 ] . Thus there is a need for well-controlled research on methadone dosing reflecting doses in common use and incorporating the changing patient population . In this controlled clinical trial we compared moderate and low methadone dosing to methadone-free treatment , providing data in a contemporary population sample of opioid addicts and examining the effect of methadone dose on cocaine as well as opioid use . Methods Participants were 247 persons who had consecutive admissions to a methadone research clinic from September 1988 through July 1990 . The mean age was 34 years , 70 % were male , and 50 % were black . Most were unmarried ( 84 % ) and unemployed ( 62 % ) . They had an average of 11 years of education , were generally legally free ( 72 % ) , and had a mean of two previous admissions for drug abuse treatment . Their primary drug of choice was intravenous heroin , and 47 % reported using cocaine in the 30 days before their application to treatment . Eligibility criteria for study participation were age between 18 and 50 years , history of intravenous opioid dependence ( including documentation of previous treatment for opioid dependence or legal involvement secondary to opioid use , a urine sample positive for opioids , and physical examination consistent with acute and chronic needle use ) , no chronic medical illnesses , absence of a major mental illness , a negative pregnancy test for women , and at least 3 months since the patient 's last treatment at the clinic . Applicants who failed to fulfill the study 's eligibility criteria were assisted in seeking an alternate treatment program . The study was approved by the institutional review board , and informed consent was obtained from each patient at the time of admission to the study . Study Procedures Applicants who fulfilled the eligibility criteria were admitted to a 6-month short-term methadone treatment program .  Participants were stratified as to race and sex and were assigned to one of three fixed-dose methadone schedules ( Figure 1 ) . Treatment group assignment , stabilization doses , and dosing schedules were double-blind for all patients and the clinic staff who had patient contact . All patients received a minimum of 35 days of active methadone during the first 5 weeks of treatment ; this was followed by a 15-week stabilization period at either 50 , 20 , or 0 mg of methadone . Thus , patients assigned to the 0-mg treatment group received 35-day methadone detoxification . During weeks 21 through 26 , the methadone dose was gradually tapered for those patients still receiving active medication because this was a short-term ( 182-day ) treatment episode . A sub sample of patients ( n = 44 ) assigned to the 0-mg treatment group received a more prolonged ( 8-week ) induction period , reaching 0 mg at the start of week 9 to compare the effects of a faster to a slower detoxification protocol . In this report data for patients in the alternate 0-mg treatment groups are collapsed . Figure 1 . Dosing schedule . Treatment Procedures Patients were assigned an individual counselor who set treatment goals and developed an individualized treatment plan . Patients were given weekly group therapy focusing on relapse prevention . On-site medical services were provided by a full-time internist and a part-time nurse practitioner . Take-home medication was provided only on legal holidays and for documented extenuating circumstances ( for example , funeral out of town for a death in the family ) . Patients who failed to attend the clinic for 3 consecutive days were discharged from treatment . Outcome Measures Treatment Retention and Compliance Treatment retention was calculated as the total number of days between the day of admission and the day of discharge , or the last day of the stable dosing period ( day 140 ) if the patient remained in treatment beyond the stable dosing period . Compliance with treatment was assessed through treatment attendance , the number of days medicated divided by days in treatment , and counseling contacts , which were based on the length ( minutes ) and number of contacts the patient had with either individual or group treatments . Urine Testing Patients provided a supervised urine sample for toxicology screening three times per week . Sample s were tested on-site using EMIT ( Syva Corporation , Palo Alto , California ) for the presence of opioids , cocaine , and benzodiazepines ; and cut-off calibration concentrations were set at 300 g/mL for each test ( morphine , benzoylecgonine , oxazepam ) . The specificity of the EMIT system ranges from 96 % to 100 % . One sample each week was r and omly selected to be sent to an outside laboratory for thin-layer chromatography analysis , which detects these same compounds and a wide variety of other less commonly abused substances . Data Analysis Retention to week 20 , days in treatment , percentage of days attended , and amount of counseling contact time were analyzed with a one-way analysis of variance with methadone dose as the grouping factor and the Tukey Honestly Significant Difference ( HSD ) test was used for post hoc analyses . Comparisons for which the critical difference value corresponding to P < 0.05 are reported as significant for this and all subsequently described analyses . Treatment survival curves were compared using the Lee-Desu statistic , with pairwise comparisons between each of the three treatment groups . The percentages of urine positive for opioids , cocaine , benzodiazepines , and any other drugs were calculated for each patient through the end of the stable dosing period . A one-factor analysis of variance with methadone dose as the grouping factor was used for each of these analyses . Results Table 1 shows the demographic features of the 247 patients enrolled in the study . The only difference across the three treatment groups on any variable was marital status ; 8 % of the patients in the 50-mg treatment group were married compared to 17 % in the 20-mg and 25 % in the 0-mg groups . Table 1 . Demographic Characteristics for Patients ( n = 247 ) Assigned to Different Methadone Doses * Treatment Retention and Compliance Orderly dose effects were seen for survival in treatment ( Figure 2 ) . Although the three treatment groups had similar rates of retention during the first 4 weeks of treatment , when all participants were receiving active methadone , retention rates diverged between weeks 4 and 8 and dose effects were seen from weeks 8 through 20 . In the survival analysis , there was an overall difference between the three curves ( P < 0.01 ) , and pairwise comparison between the 50-mg and 0-mg treatment groups differed significantly ( P < 0.01 ) ; the differences between the 50-mg and 20-mg , and 20-mg and 0-mg treatment groups approached significance ( P = 0.1 and P = 0.08 , respectively ) . At week 20 , the end of the stable dosing period , retention was 52.4 % for the 50-mg , 41.5 % for the 20-mg , and 21.0 % for the 0-mg groups ( 50 versus 0 and 20 versus 0 , P < 0.05 ; 50 versus 20 , P > 0.05 ) . Figure 2 . Retention in treatment . n The number of days retained in treatment was also dose related ( P < 0.01 ) ; Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients . As hypothesized , 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use , but higher dosage did not improve treatment retention . Self-reported illicit opioid use declined substantially in all groups , but by the third month , significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone . From an initial average of $ 1860/month , month 3 usage dropped to $ 41 ( methadone 65 mg ) , $ 73 ( methadone 35 mg ) , $ 118 ( buprenorphine 6 mg ) , and $ 35I/month ( buprenorphine 2 mg ) . Days of use also dropped from 29 days to 1.7 ( methadone 65 mg ) , 2.8 ( methadone 35 mg ) , 4.0 ( buprenorphine 6 mg ) , and 6.6 days/month ( buprenorphine 2 mg ) . This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial , with 7.2 days/month and $ 235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $ 65/month for the other three groups . Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms . Our secondary hypothesis , that buprenorphine would be equivalent to methadone in efficacy , was not supported . Treatment retention was significantly better on methadone ( 20 us . 
    Output:
    
Opioid use ( self reported ) , times/w - RCTs : high vs low doses WMD= -2.00 [ -4.77,0.77 ] high vs middle doses WMD= -1.89[-3.43 , -0.35 ] Opioid abstinence , ( urine based ) at > 3 - 4 w - RCTs : high vs low ones : RR=1.59 [ 1.16,2.18 ] high vs middle doses RR=1.51[0.63,3.61 ] Cocaine abstinence ( urine based ) at > 3 - 4 w - RCTs : high vs low doses RR=1.81 [1.15,2.85]Overdose mortality - CPSs : high dose vs low dose at 6 years follow up : RR=0.29 [ 0.02 - 5.34 ] high dose vs middle dose at 6 years follow up : RR=0.38 [ 0.02 - 9.34 ] middle dose vs low dose at 6 years follow up : RR=0.57 [ 0.06 - 5.06 ] REVIEW ER 'S CONCLUSIONS Methadone dosages ranging from 60 to 100 mg/day are more effective than lower dosages in retaining patients and in reducing use of heroin and cocaine during treatment .