***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: Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Few clinical trials include sex as a factor . This analysis explored within-sex differences in response to opioid agonist medications . Males and females r and omly assigned to buprenorphine , LAAM , or methadone  were compared on opioid use and retention in treatment . Females receiving buprenorphine had less objective drug use than females receiving methadone , while males receiving LAAM had less objective drug use than males receiving buprenorphine . Retention in treatment was longer for both sexes receiving methadone versus LAAM . Within-subject change results indicate that all three medications benefit both sexes . Clinical trials should be design ed to examine the impact of sex on outcomes BACKGROUND Genetic variations of the dopamine and opioid receptors could influence the response to methadone maintenance treatment ( MMT ) . METHODS We included 238 MMT patients according to their response to treatment and methadone dosing , along with 217 subjects without substance dependence . All were genotyped for polymorphisms of the dopamine D1 , D2 , micro-opioid and delta-opioid receptor genes . RESULTS The polymorphisms of the micro-opioid ( 118A > G ) , delta-opioid ( 921T > C ) , dopamine D1 ( DdeI ) and D2 ( TaqI A ) receptor genes were not associated with response to MMT and methadone dosing , whereas an association was found with the dopamine D2 receptor ( DRD2 ) 957C > T polymorphism . The 957CC carriers were more frequently non-responders to treatment ( OR=2.4 ; p=0.02 ) and presented a fourfold shorter period of negative urine screening ( p=0.02 ) . No significant differences in allele frequencies were observed between the MMT patients and the control group , suggesting no association of the analyzed polymorphisms with opioid dependence . CONCLUSIONS These results suggest that DRD2 genotype may contribute to the underst and ing of the interindividual variability to the response to MMT OBJECTIVE Women represent the largest percentage of new HIV infections globally . Yet , no large-scale studies have examined the experience of pain and its treatment in women living with HIV . DESIGN This study used structural equation modeling to examine sex differences in pain and the use and misuse of prescription analgesics in a representative sample of HIV+ persons in the United Stated within a prospect i ve , longitudinal design . OUTCOME MEASURES Bodily pain subscale of the Short-Form 36 and Modified Short Form of the World Health Organization 's Composite International Diagnostic Interview ( opioid misuse ) . RESULTS Women reported more pain than men over a roughly 6-month period regardless of mode of HIV transmission or prior drug use history . Men acknowledged more misuse of prescription analgesics over an approximate 1-year period compared with women , after taking into account pain , use of analgesics specifically for pain , and drug use history . Weaker associations between pain and use of analgesics specifically for pain that persisted over time were found among women compared with men . For both men and women , pain was stable over time . Problem drug use history exerted significant direct and indirect effects on pain , opioid misuse , and pain-specific analgesic use across sex . CONCLUSION The current findings are consistent with prior evidence indicating female pain predominance as well as the undertreatment of pain among women with HIV . Efforts should be made to improve the assessment and long-term management of pain in HIV+ persons INTRODUCTION We conducted a follow-up study to evaluate the outcome of a heroin-dependent population 25 years after their first enrollment in methadone maintenance treatment ( MMT ) .  We assessed mortality in the sample plus actual drug use , treatment , and medical factors associated with drug dependence , focusing on possible gender differences . METHODS Prospect i ve follow-up study of 214 heroin-dependent patients consecutively admitted for MMT between 1980 and 1984 in the Asturias Public Health Service . The st and ardized mortality ratio ( SMR ) and 95 % confidence interval ( CI ) were calculated . An ad-hoc protocol on drug misuse and treatment , drug-related morbidity and Clinical Global Impression ( CGI ) scores were assessed in the survivors ' sample . RESULTS Information was received on 159 subjects , 106 of whom were deceased . Men accounted for 76.2 % of the study cohort . Over the 25-year follow-up period , the SMR was 22.51 ( 95 % CI=22.37 - 22.64 ) . In the survivors sample , 39.6 % were still enrolled in MMT ; human immunodeficiency virus ( HIV ) was diagnosed in 47.2 % and hepatitis B/C in 81.1 % ; current heroin use was reported by 22.6 % . There were no gender differences in mortality or HIV and hepatitis B/C status . None of the female survivors were using heroin at the 25-year follow-up compared with 31.1 % of males . CONCLUSIONS This study confirms the high mortality of heroin addicts even after enrollment in MMT . Severity of the addiction in terms of mortality was similar in both genders . Women who survived the 25-year follow-up were more likely to have stopped using heroin than men Abstract We prospect ively compared gender outcome among 470 MMT patients admitted between June 1993 and Dec 2002 . Urine sample s were analyzed for drug abuse after one month and after one year . On admission females 131(27.9 % ) were significantly younger ( 34.5 ± 7.5 years ) than males 339(72.1 % ) ( 37.3 ± 8.3 years ) ( ANOVA;F = 11 , p = 0.001 ) and had significantly higher cocaine abuse ( 20 % vs. 11.3 % ) ( Fisher 's Exact Test , p = 0.02 ) . After one year , groups had : ( a ) similar retention in treatment ( 76.3%-females , 72.6%-males ) , ( b ) stop in opiate abuse ( 65%-females , 65.3%-males ) , ( c ) a net decrease in cocaine abuse ( % positive that became negative minus % negative that became positive ) ( 68.0%-females , 51.6%-males ) . Females who were admitted to treatment while pregnant ( n = 45 ) were significantly younger ( 31.5 ± 5.4 years ) compared to 86 non-pregnant ( 36.1 ± 7.9 , ANOVA F = 12.1 , p = 0.001 ) . We concluded that compared to males , females started MMT younger and had a higher proportion of cocaine abuse even though females ' outcome were similar to males ' 
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Discussion We anticipate that this review will highlight how men and women differ in  methadone treatment outcomes and allow us to generate conclusions that can be applied to treatment in a clinical setting .