The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs.

BACKGROUND: In South Africa, an estimated 11% of the population have high alcohol use, a major risk factor for TB. Alcohol and other substance use are also associated with poor treatment response, with a potential mechanism being altered TB drug pharmacokinetics. OBJECTIVES: To investigate the impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs in participants with pulmonary TB. METHODS: We prospectively enrolled participants ≥15 years old, without HIV, and initiating drug-susceptible TB treatment in Worcester, South Africa. Alcohol use was measured via self-report and blood biomarkers. Other illicit substances were captured through a urine drug test. Plasma samples were drawn 1 month into treatment pre-dose, and 1.5, 3, 5 and 8 h post-dose. Non-linear mixed-effects modelling was used to describe the pharmacokinetics of rifampicin, isoniazid, pyrazinamide and ethambutol. Alcohol and drug use were tested as covariates. RESULTS: The study included 104 participants, of whom 70% were male, with a median age of 37 years (IQR 27-48). Alcohol use was high, with 42% and 28% of participants having moderate and high alcohol use, respectively. Rifampicin and isoniazid had slightly lower pharmacokinetics compared with previous reports, whereas pyrazinamide and ethambutol were consistent. No significant alcohol use effect was detected, other than 13% higher ethambutol clearance in participants with high alcohol use. Methaqualone use reduced rifampicin bioavailability by 19%. CONCLUSION: No clinically relevant effect of alcohol use was observed on the pharmacokinetics of first-line TB drugs, suggesting that poor treatment outcome is unlikely due to pharmacokinetic alterations. That methaqualone reduced rifampicin means dose adjustment may be beneficial.

Patient and provider perceptions of the relationship between alcohol use and TB and readiness for treatment: a qualitative study in South Africa.

BACKGROUND: Unhealthy alcohol use is widespread in South Africa and has been linked to tuberculosis (TB) disease and poor treatment outcomes. This study used qualitative methods to explore the relationship between TB and alcohol use during TB treatment. METHODS: Focus group discussions (FGDs) were conducted with 34 participants who had previous or current drug-susceptible TB and self-reported current alcohol use. Eight interviews were conducted with healthcare workers who provide TB services in Worcester, South Africa. RESULTS: In this rural setting, heavy episodic drinking is normalized and perceived to be related to TB transmission and decreased adherence to TB medication. Both healthcare workers and FGD participants recommended the introduction of universal screening, brief interventions, and referral to specialized care for unhealthy alcohol use. However, participants also discussed barriers to the provision of these services, such as limited awareness of the link between alcohol and TB. Healthcare workers also specified resource constraints, while FGD participants or patients mentioned widespread stigma towards people with alcohol concerns. Both FGD participants and health providers would benefit from education on the relationship between TB and unhealthy alcohol use and had specific recommendations about interventions for alcohol use reduction. Healthcare workers also suggested that community health worker-delivered interventions could support access to and engagement in both TB and alcohol-related services. CONCLUSION: Findings support strengthening accessible, specialized services for the identification and provision of interventions and psychosocial services for unhealthy alcohol use among those with TB.

Binge drinking and condom negotiation behaviours among adolescent girls and young women living in Cape Town, South Africa: sexual control and perceived personal power.

BACKGROUND: Condom use among young people in South Africa has declined in recent years and adolescent girls and young women continue to bear the highest incidence of HIV in the country. Young women who have dropped out of school may be more at risk because of traditional gender norms that create substantial power imbalances and a lack of power to negotiate condom use with their male partners, especially when using alcohol and other drugs. METHODS: This study presents an analysis of baseline data provided by 500 adolescent girls and young women (AGYW) from Cape Town communities between November 2016 and November 2018 who were reached for a cluster-randomised trial conducted to assess the efficacy of an evidence-based, young woman-focused intervention seeking to reduce HIV risk and substance use behaviours. The analysis focuses on associations between binge drinking, condom use, and sexual negotiation, including impaired sex (any substance use at last sex). RESULTS: AGYW who reported frequent condom negotiation with their partners were 8.92 times (95% CI: [4.36, 18.24]) as likely to use a condom when alcohol or other drugs were not used at last sex and 5.50 times (95% CI: [2.06, 14.72]) as likely when alcohol or other drugs were used at last sex (p < 0.05). AGYW who reported frequent binge drinking in the past month (n = 177) had significantly reduced odds of condom use at last sex, irrespective of whether the sex was impaired (OR 0.60, 95% CI: [0.49, 0.73]) or not impaired (OR 0.69, 95% CI: [0.60, 0.81]). DISCUSSION: The findings highlight the need for interventions that reach AGYW in South Africa by specifically aiming to educate AGYW about the effect of binge drinking on negotiating power in their relationships, thus providing them with the knowledge and skills to increase agency regarding condom use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02974998 (recruitment completed). 29/11/2016.

Factors associated with current substance use among a sample of homeless individuals in Cape Town, South Africa: a secondary data analysis.

Homelessness is a global issue that is often associated with substance use. Research on this relationship in low- to middle-income countries (LMIC) is limited. We aimed to explore which factors are associated with substance use through secondary data analysis of a sample of 472 adults who attended services for homeless individuals in Cape Town, South Africa. Logistic regression was utilized to investigate if length of homelessness was associated with current alcohol and drug use respectively, after accounting for other factors. Current drug use (44.9%) was higher than current alcohol use (22.7%) and the most prevalent lifetime drug was methamphetamine (32.6%). After adjusting for lifetime substance use, and source of income, length of homelessness was not significantly associated with current alcohol use (less than on year: OR = 2.60; 95% CI: 0.78-8.66; one or more years: OR = 0.90; 95% CI: 0.32-2.57) or current drug use (less than one year: OR = 0.78; 95% CI: 0.41-1.47; one year or more: OR = 1.04; 95% CI: 0.56-1.93). These results highlight the need to further investigate other factors that may influence current alcohol or drug use among populations at risk of being homeless, and to utilize validated measures of substance and other mental health conditions.

Methods for handling missing data in serially sampled sputum specimens for mycobacterial culture conversion calculation.

BACKGROUND: The occurrence and timing of mycobacterial culture conversion is used as a proxy for tuberculosis treatment response. When researchers serially sample sputum during tuberculosis studies, contamination or missed visits leads to missing data points. Traditionally, this is managed by ignoring missing data or simple carry-forward techniques. Statistically advanced multiple imputation methods potentially decrease bias and retain sample size and statistical power. METHODS: We analyzed data from 261 participants who provided weekly sputa for the first 12 weeks of tuberculosis treatment. We compared methods for handling missing data points in a longitudinal study with a time-to-event outcome. Our primary outcome was time to culture conversion, defined as two consecutive weeks with no Mycobacterium tuberculosis growth. Methods used to address missing data included: 1) available case analysis, 2) last observation carried forward, and 3) multiple imputation by fully conditional specification. For each method, we calculated the proportion culture converted and used survival analysis to estimate Kaplan-Meier curves, hazard ratios, and restricted mean survival times. We compared methods based on point estimates, confidence intervals, and conclusions to specific research questions. RESULTS: The three missing data methods lead to differences in the number of participants achieving conversion; 78 (32.8%) participants converted with available case analysis, 154 (64.7%) converted with last observation carried forward, and 184 (77.1%) converted with multiple imputation. Multiple imputation resulted in smaller point estimates than simple approaches with narrower confidence intervals. The adjusted hazard ratio for smear negative participants was 3.4 (95% CI 2.3, 5.1) using multiple imputation compared to 5.2 (95% CI 3.1, 8.7) using last observation carried forward and 5.0 (95% CI 2.4, 10.6) using available case analysis. CONCLUSION: We showed that accounting for missing sputum data through multiple imputation, a statistically valid approach under certain conditions, can lead to different conclusions than naïve methods. Careful consideration for how to handle missing data must be taken and be pre-specified prior to analysis. We used data from a TB study to demonstrate these concepts, however, the methods we described are broadly applicable to longitudinal missing data. We provide valuable statistical guidance and code for researchers to appropriately handle missing data in longitudinal studies.

'We have goals but [it is difficult]'. Barriers to antiretroviral therapy adherence among women using alcohol and other drugs living with HIV in South Africa.

BACKGROUND: Women living with HIV who misuse alcohol and live in economically disadvantaged settings in South Africa experience a multitude of contextual barriers as they navigate the HIV care continuum. The Women's Health CoOp (WHC), a brief, woman-focused, behavioural, evidence-based intervention, has been shown to be effective in reducing heavy drinking and improving HIV-related outcomes among this key population. However, these women face other broader socioecological barriers to antiretroviral therapy (ART) adherence. METHODS: The WHC was implemented in a modified, stepped-wedge implementation science trial in public health clinics and substance use treatment programmes in Cape Town, South Africa. A qualitative substudy was conducted to explore barriers to HIV treatment adherence among women enrolled in this trial. Eight focus group discussions were conducted with 69 participants 6 months after completion of the WHC workshops. Focus groups were audio-recorded (with consent), transcribed verbatim and analysed using a thematic approach. RESULTS: The mean age of the participants was 33 years and the mean self-reported number of drinks per day was 13. The main contextual factors influencing participants' ART adherence were intrapersonal-level factors (substance use, financial constraints, food insecurity; community-level factors (anticipated and enacted stigma, community violence) and institutional-level factors (patient-provider relationships, health facility barriers, environmental stigma). CONCLUSION: Comprehensive interventions addressing the contextual barriers and unique challenges faced by women who misuse alcohol in low-resource settings that intersect with HIV treatment nonadherence should be implemented in tandem with successful biobehavioural HIV interventions for long-term effectiveness and sustainability. PATIENT OR PUBLIC CONTRIBUTION: Our South African community collaborative board has been involved throughout this study; participants and clinic staff voices have been essential in our interpretation of these findings.

"Because all mothers is not the same": The development and implementation of an in loco parentis informed consent procedure to enroll adolescent girls and young women to participate in HIV research.

INTRODUCTION: South Africa has one of the highest incidences of HIV among adolescent girls and young women (AGW), ages 15-24, and recent research has focused on developing interventions for HIV prevention. However, the South African National Health Act requires those under 18 years of age to obtain a guardian's permission to participate in research. Limiting research enrolment to AGYW who can obtain guardian consent may lead to non-representative findings. Therefore, innovative, inclusive consent approaches that protect AGYW from the risks of research are needed. METHODS: This report details the development and implementation of an approach called the in loco parentis (in place of parent) consent procedure. In loco parentis consent provides a vehicle for adolescent participation that protects adolescents from potential social harms. The in loco parentis consent procedure does not seek to obtain independent minor consent but seeks to obtain permission for the minor to participate in research from a trusted adult who is not a minor's parent or legal guardian. This report also qualitatively explores the experiences of 31 AGYW who were recruited into a behavioral HIV prevention study using this method. RESULTS: Findings suggest that the in loco parentis consent procedure is a feasible and acceptable method to inclusively AGYW in HIV research. CONCLUSIONS: The in loco parentis procedure may provide a more inclusive strategy to recruit AGYW for HIV research to increase the generalizability of findings.

Dihydrocodeine for detoxification and maintenance treatment in individuals with opiate use disorders.

BACKGROUND: Medical treatment and detoxification from opiate disorders includes oral administration of opioid agonists. Dihydrocodeine (DHC) substitution treatment is typically low threshold and therefore has the capacity to reach wider groups of opiate users. Decisions to prescribe DHC to patients with less severe opiate disorders centre on its perceived safety, reduced toxicity, shorter half-life and more rapid onset of action, and potential retention of patients. This review set out to investigate the effects of DHC in comparison to other pharmaceutical opioids and placebos in the detoxification and substitution of individuals with opiate use disorders. OBJECTIVES: To investigate the effectiveness of DHC in reducing illicit opiate use and other health-related outcomes among adults compared to other drugs or placebos used for detoxification or substitution therapy. SEARCH METHODS: In February 2019 we searched Cochrane Drugs and Alcohol's Specialised Register, CENTRAL, PubMed, Embase and Web of Science. We also searched for ongoing and unpublished studies via ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and Trialsjournal.com. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies. SELECTION CRITERIA: We included randomised controlled trials that evaluated the effect of DHC for detoxification and maintenance substitution therapy for adolescent (aged 15 years and older) and adult illicit opiate users. The primary outcomes were abstinence from illicit opiate use following detoxification or maintenance therapy measured by self-report or urinalysis. The secondary outcomes were treatment retention and other health and behaviour outcomes. DATA COLLECTION AND ANALYSIS: We followed the standard methodological procedures that are outlined by Cochrane. This includes the GRADE approach to appraise the quality of evidence. MAIN RESULTS: We included three trials (in five articles) with 385 opiate-using participants that measured outcomes at different follow-up periods in this review. Two studies with 150 individuals compared DHC with buprenorphine for detoxification, and one study with 235 participants compared DHC to methadone for maintenance substitution therapy. We downgraded the quality of evidence mainly due to risk of bias and imprecision. For the two studies that compared DHC to buprenorphine, we found low-quality evidence of no significant difference between DHC and buprenorphine for detoxification at six-month follow-up (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.25 to 1.39; P = 0.23) in the meta-analysis for the primary outcome of abstinence from illicit opiates. Similarly, low-quality evidence indicated no difference for treatment retention (RR 1.29, 95% CI 0.99 to 1.68; P = 0.06). In the single trial that compared DHC to methadone for maintenance substitution therapy, the evidence was also of low quality, and there may be no difference in effects between DHC and methadone for reported abstinence from illicit opiates (mean difference (MD) -0.01, 95% CI -0.31 to 0.29). For treatment retention at six months' follow-up in this single trial, the RR calculated with an intention-to-treat analysis also indicated that there may be no difference between DHC and methadone (RR 1.04, 95% CI 0.94 to 1.16). The studies that compared DHC to buprenorphine reported no serious adverse events, while the DHC versus methadone study reported one death due to methadone overdose. AUTHORS' CONCLUSIONS: We found low-quality evidence that DHC may be no more effective than other commonly used pharmacological interventions in reducing illicit opiate use. It is therefore premature to make any conclusive statements about the effectiveness of DHC, and it is suggested that further high-quality studies are conducted, especially in low- to middle-income countries.

The adaptation of an evidence-based brief intervention for substance-using adolescents and their caregivers.

Objective: Adolescent substance use is prevalent and associated with additional risk behaviours. Research shows that evidence-based brief interventions with adolescents and their main caregiver may mitigate the progression of substance use. Method: We used the ADAPT-ITT framework to develop a needs-based, culturally-sensitive intervention. Five focus groups with adolescents (n = 30), three focus groups with separate main caregivers of adolescents who use substances (n = 21), key informant interviews and an expert meeting, were conducted. Results: Adolescents described the need to decrease risk behaviours, while adolescents and caregivers requested additional support. The core components of the original intervention were retained, with some additions. The newly adapted RAD-PAL intervention was viewed as acceptable. Conclusion: Despite apparent acceptability, we need to test feasibility and efficacy in a trial.

Acceptability and feasibility of a brief substance use intervention for adolescents in Cape Town, South Africa: A pilot study.

Substance use is prevalent among South African adolescents, but few interventions exist to reduce risk of harm. This study assesses the feasibility, acceptability and preliminary effects of a brief intervention for reducing adolescent substance use and other risk behaviours. This single-arm feasibility test recruited 30 substance-using adolescents and their primary caregiver. Participants received separate interventions (2 sessions for adolescents, 1 session for caregivers), with a subsample randomly selected for post-intervention interviews. Feasibility was measured by the proportion of eligible adolescents who were enrolled and retained in the study. Interviews explored acceptability, and changes in outcomes from baseline to 1-month follow-up assessed preliminary effects of the intervention. Thirty of 43 (69.8%) eligible adolescents and their caregivers were enrolled, with 29 adolescents (96.7%) and 28 caregivers (93.3%) completing the intervention. Twenty-eight adolescents (93.3%) and 29 caregivers (96.7%) were retained at follow-up. Frequency of alcohol, cannabis use and delinquent-type behaviours decreased significantly from baseline to follow-up. Participants appreciated the intervention content and delivery and felt that it facilitated behaviour change. Suggestions for improving the intervention were provided. This study found that the intervention is feasible, acceptable and had promising effects on adolescent behaviour. Efficacy must be established with a randomised controlled trial.

Measuring Relationship Functioning in South African Couples: A Strategy for Improving HIV Prevention Efforts.

Over the past decade there has been increased focus on targeting couples in HIV prevention efforts, particularly in sub-Saharan Africa where HIV transmission primarily occurs through heterosexual contact, in the context of intersecting alcohol use and intimate partner violence (IPV). However, little is known about couples' general relationship functioning. This understanding is needed to augment couple-based HIV prevention programs and address risk for IPV. This paper presents data on domains of relationship functioning with 300 South African couples who were recruited for an HIV prevention study. Exploratory and confirmatory factor analyses were conducted to determine the relevance of 17 individual items, as well as the overall factor structure of the questions. Results revealed three independent factors of relationship functioning: relationship satisfaction, arguing, and open communication; an overarching construct of relationship functioning for these three domains was not observed in the data. Results provide insight into the structure of relationship functioning questions and subscales that can be used to assess South African adult romantic relationships. This may allow for a greater focus on aspects of relationships within couple-based HIV prevention programs going forward.

Adolescent female school dropouts who use drugs and engage in risky sex: effects of a brief pilot intervention in Cape Town, South Africa.

Female adolescents from socioeconomically underserved communities in Cape Town, South Africa, who have dropped out of school, use substances, and engage in risky sex behaviour are at risk of HIV. Tailored gender-focused HIV behavioural interventions for this key population are needed to mitigate these risk factors. A pilot trial of a woman-focused risk-reduction intervention for adolescents was conducted (N = 100), with a one-month follow-up appointment. Participants in the intervention group attended two group workshops. Data were examined for significant differences within and between the groups. At baseline, 94% of participants tested positive for cannabis, 17% were HIV-positive and 11% were pregnant. Ninety-two participants returned for 1-month follow-up. At follow-up, the proportion who tested positive for cannabis use decreased significantly in both the intervention (p = 0.07) and control groups (p = 0.04). Impaired sex with any partner (p = 0.02), or with main partner (p = 0.06) decreased among the intervention group. Impaired sex with a main partner was less likely in the intervention group (p = 0.07) in the regression model. In conclusion, findings indicate a need for HIV prevention interventions among out-of-school female adolescents. Intervention acceptability was high, and there were some decreases in sexual risk behaviour among intervention participants which is promising. Future intervention research with this key population involving larger sample sizes and longer follow-up periods will help to determine intervention efficacy.

Accuracy and Utility of the AUDIT-C with Adolescent Girls and Young Women (AGYW) Who Engage in HIV Risk Behaviors in South Africa.

Hazardous drinking is a risk factor associated with sexual risk, gender-based violence, and HIV transmission in South Africa. Consequently, sound and appropriate measurement of drinking behavior is critical to determining what constitutes hazardous drinking. Many research studies use internal consistency estimates as the determining factor in psychometric assessment; however, deeper assessments are needed to best define a measurement tool. Rasch methodology was used to evaluate a shorter version of the Alcohol Use Disorders Identification Test, the AUDIT-C, in a sample of adolescent girls and young women (AGYW) who use alcohol and other drugs in South Africa (n =100). Investigations of operational response range, item fit, sensitivity, and response option usage provide a richer picture of AUDIT-C functioning than internal consistency alone in women who are vulnerable to hazardous drinking and therefore at risk of HIV. Analyses indicate that the AUDIT-C does not adequately measure this specialized population, and that more validation is needed to determine if the AUDIT-C should continue to be used in HIV prevention intervention studies focused on vulnerable adolescent girls and young women.

The Young Women's Health CoOp in Cape Town, South Africa: Study protocol for a cluster-randomised trial for adolescent women at risk for HIV.

BACKGROUND: South Africa remains the global epicentre of HIV infection, and adolescent women have the highest incidence of HIV in the country. South Africa also has high rates of alcohol and other drug (AOD) use, violence, and gender inequality. Violence converges with AOD use, gender inequities and other disparities, such as poverty, to increase sexual risk and poor educational attainment for adolescent women. This study seeks to test the efficacy of peer recruitment and cofacilitation of the Young Women's Health CoOp (YWHC), a comprehensive gender-focused intervention to reduce HIV risk behaviours and increase the uptake of HIV counselling and testing (HCT) among out-of-school, adolescent women who use AODs. The YWHC is facilitated by local research staff and supported by peers. METHODS: This cluster-randomised trial is enrolling participants into two arms: a control arm that receives standard HCT, and an intervention arm that receives the YWHC. Participants are enrolled from 24 economically disadvantaged communities in Cape Town, South Africa. These geographically distinct communities serve as clusters that are the units of randomisation. This study uses adolescent peer role models and research field staff to recruit marginalised adolescent women. At baseline, participants complete a questionnaire and biological testing for HIV, recent AOD use, and pregnancy. The core intervention is delivered in the month following enrollment, with linkages to health services and educational programmes available to participants throughout the follow-up period. Follow-up interviews and biological testing are conducted at 6 and 12 months post enrollment. DISCUSSION: The study findings will increase knowledge of the efficacy of a comprehensive HCT, gender-focused programme in reducing AOD use, victimisation, and sexual risk behaviour and increase uptake services for out-of-school, adolescent women who use AODs. The trial results could lead to wider implementation of the YWHC for vulnerable adolescent women, a key population often neglected in health services. TRIAL REGISTRATION: Trial registration no: NCT02974998 , November 29, 2016.

Aggressive behaviour among drug-using women from Cape Town, South Africa: ethnicity, heavy alcohol use, methamphetamine and intimate partner violence.

BACKGROUND: Women have generally been found to be the victims of violence, but scant attention has been paid to the characteristics of women who perpetrate aggression and violence. In South Africa, violence is a prevalent societal issue, especially in the Western Cape. METHOD: This study aimed at identifying factors that were associated with aggression among a sample of 720 substance-using women. We conducted multivariate logistic regression to identify factors that are significantly associated with these behaviours. RESULTS: Ethnicity (Wald Χ2 = 17.07(2), p < 0.01) and heavy drinking (Wald Χ2 = 6.60 (2), p = 0.01) were significantly related to verbal aggression, methamphetamine use was significantly related to physical (Wald Χ2 = 2.73 (2), p = 0.01) and weapon aggression (Wald Χ2 = 7.94 (2), p < 0.01) and intimate partner violence was significantly related to verbal (Wald Χ2 = 12.43 (2), p < 0.01) and physical aggression (Wald Χ2 = 25.92 (2), p < 0.01). CONCLUSIONS: The findings show high levels of aggression among this sample, and highlight the need for interventions that address methamphetamine, heavy drinking and intimate partner violence among vulnerable substance-using women.

Barriers and facilitators to implementing an evidence-based woman-focused intervention in South African health services.

BACKGROUND: Since the beginning of the HIV epidemic, numerous behavior change, risk-reduction, and biomedical interventions have been developed and tested. While some of these interventions have shown to be efficacious in randomized trials, it often takes almost two decades for an intervention to be translated into practice. Meanwhile, South Africa continues to have among the highest prevalence of HIV globally, with women of childbearing age bearing the burden of the epidemic. Given the urgency of the HIV epidemic among vulnerable women in South Africa, it is imperative that evidence-based interventions be implemented rapidly into practice. This study presents a first step toward examining the acceptability and feasibility of implementing the Women's Health CoOp (WHC) in clinics and substance abuse rehab settings in Cape Town, South Africa. METHODS: We conducted focus group discussions with women who use substances and with service providers, we also conducted in-depth interviews with health service planners. Our goal was to examine implementation and clinical outcomes associated with delivery of the WHC across clinics and substance abuse rehab programs. RESULTS: All participants agreed on the need for the WHC. Perceived facilitators to implementing the WHC included the recognizable need for programs to empower women and to build the capacity of staff to address issues of substance use, sexual risk, and intimate partner violence. Participants also identified potential barriers to women engaging with this program, including the stigma women experience when seeking services and the lack of person-centered care at healthcare facilities. CONCLUSIONS: In a country with the largest number of women of childbearing age living with HIV, an evidence-based woman-focused intervention that comprehensively addresses women's risk for suboptimal antiretroviral adherence may be essential for reducing HIV incidence. However, potential barriers to implementing the WHC successfully must be addressed before the program can be fully integrated into the services delivered by healthcare facilities. TRIAL REGISTRATION: Clinical trials NCT02733003 . Date of Registration: January 21, 2016, registered retroactively after participant enrollment.

Brief school-based interventions and behavioural outcomes for substance-using adolescents.

BACKGROUND: Adolescent substance use is a major problem in and of itself, and because it acts as a risk factor for other problem behaviours. As substance use during adolescence can lead to adverse and often long-term health and social consequences, it is important to intervene early in order to prevent progression to more severe problems. Brief interventions have been shown to reduce problematic substance use among adolescents and are especially useful for individuals who have moderately risky patterns of substance use. Such interventions can be conducted in school settings. This review set out to evaluate the effectiveness of brief school-based interventions for adolescent substance use. OBJECTIVES: To evaluate the effectiveness of brief school-based interventions in reducing substance use and other behavioural outcomes among adolescents compared to another intervention or assessment-only conditions. SEARCH METHODS: We conducted the original literature search in March 2013 and performed the search update to February 2015. For both review stages (original and update), we searched 10 electronic databases and six websites on evidence-based interventions, and the reference lists of included studies and reviews, from 1966 to February 2015. We also contacted authors and organisations to identify any additional studies. SELECTION CRITERIA: We included randomised controlled trials that evaluated the effects of brief school-based interventions for substance-using adolescents.The primary outcomes were reduction or cessation of substance use. The secondary outcomes were engagement in criminal activity and engagement in delinquent or problem behaviours related to substance use. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures outlined by The Cochrane Collaboration, including the GRADE approach for evaluating the quality of evidence. MAIN RESULTS: We included six trials with 1176 adolescents that measured outcomes at different follow-up periods in this review. Three studies with 732 adolescents compared brief interventions (Bls) with information provision only, and three studies with 444 adolescents compared Bls with assessment only. Reasons for downgrading the quality of evidence included risk of bias of the included studies, imprecision, and inconsistency. For outcomes that concern substance abuse, the retrieved studies only assessed alcohol and cannabis. We generally found moderate-quality evidence that, compared to information provision only, BIs did not have a significant effect on any of the substance use outcomes at short-, medium-, or long-term follow-up. They also did not have a significant effect on delinquent-type behaviour outcomes among adolescents. When compared to assessment-only controls, we found low- or very low-quality evidence that BIs reduced cannabis frequency at short-term follow-up in one study (standardised mean difference (SMD) -0.83; 95% confidence interval (CI) -1.14 to -0.53, n = 269). BIs also significantly reduced frequency of alcohol use (SMD -0.91; 95% CI -1.21 to -0.61, n = 242), alcohol abuse (SMD -0.38; 95% CI -0.7 to -0.07, n = 190) and dependence (SMD -0.58; 95% CI -0.9 to -0.26, n = 190), and cannabis abuse (SMD -0.34; 95% CI -0.65 to -0.02, n = 190) at medium-term follow-up in one study. At long-term follow-up, BIs also reduced alcohol abuse (SMD -0.72; 95% CI -1.05 to -0.40, n = 181), cannabis frequency (SMD -0.56; 95% CI -0.75 to -0.36, n = 181), abuse (SMD -0.62; 95% CI -0.95 to -0.29, n = 181), and dependence (SMD -0.96; 95% CI -1.30 to -0.63, n = 181) in one study. However, the evidence from studies that compared brief interventions to assessment-only conditions was generally of low quality. Brief interventions also had mixed effects on adolescents' delinquent or problem behaviours, although the effect at long-term follow-up on these outcomes in the assessment-only comparison was significant (SMD -0.78; 95% CI -1.11 to -0.45). AUTHORS' CONCLUSIONS: We found low- or very low-quality evidence that brief school-based interventions may be more effective in reducing alcohol and cannabis use than the assessment-only condition and that these reductions were sustained at long-term follow-up. We found moderate-quality evidence that, when compared to information provision, brief interventions probably did not have a significant effect on substance use outcomes. It is premature to make definitive statements about the effectiveness of brief school-based interventions for reducing adolescent substance use. Further high-quality studies examining the relative effectiveness of BIs for substance use and other problem behaviours need to be conducted, particularly in low- and middle-income countries.

Characterizing male-female interactions using natural genetic variation in Drosophila melanogaster.

Drosophila melanogaster females commonly mate with multiple males establishing the opportunity for pre- and postcopulatory sexual selection. Traits impacting sexual selection can be affected by a complex interplay of the genotypes of the competing males, the genotype of the female, and compatibilities between the males and females. We scored males from 96 2nd and 94 3rd chromosome substitution lines for traits affecting reproductive success when mated with females from 3 different genetic backgrounds. The traits included male-induced female refractoriness, male remating ability, the proportion of offspring sired under competitive conditions and male-induced female fecundity. We observed significant effects of male line, female genetic background, and strong male by female interactions. Some males appeared to be "generalists" and performed consistently across the different females; other males appeared to be "specialists" and performed very well with a particular female and poorly with others. "Specialist" males did not, however, prefer to court those females with whom they had the highest reproductive fitness. Using 143 polymorphisms in male reproductive genes, we mapped several genes that had consistent effects across the different females including a derived, high fitness allele in Acp26Aa that may be the target of adaptive evolution. We also identified a polymorphism upstream of PebII that may interact with the female genetic background to affect male-induced refractoriness to remating. These results suggest that natural variation in PebII might contribute to the observed male-female interactions.

Sexual HIV risk among substance-using female commercial sex workers in Durban, South Africa.

This study examined data collected from a sample of female sex workers (FSWs) during the first two years of a brief risk-reduction intervention for vulnerable populations that focused on substance use and HIV risk-related behaviours (2007-2009) as part of a rapid assessment and response evaluation study. In 2007, in collaboration with a local non-governmental organisation (NGO), an initiative was begun to roll out targeted harm reduction strategies for drug-using street based FSWs in Durban, South Africa. Data were collected on demographic characteristics, substance use and HIV risk behaviours to tailor these harm reduction strategies with participants. Over the first two years of the intervention, data were collected from 646 FSWs: 428 who reported being at low risk for HIV and 218 who reported being at high risk for HIV (defined as engaging in unprotected sex with sexual partners in the past 90 days). FSWs who had previously been diagnosed with HIV or a sexually transmitted disease (STD) were significantly less likely to report engaging in unprotected sex. Those who used over-the-counter or prescription (OTC/PRE) drugs reported engaging in unprotected sex significantly more often than FSWs who did not use these substances, while those who used heroin were less likely to report unprotected sex. The findings are encouraging in that those who are aware of their HIV status are less likely to engage in risky sexual behaviour, and therefore HIV testing and counselling is recommended. It indicates the need to identify strategies to encourage the likelihood of all FSWs, particularly those who are HIV-positive, to use condoms. It also encourages further research to investigate specific substances as possible predictors of high risk behaviours in high-risk populations of sex workers.

Alcohol and drug use outcomes among vulnerable women living with HIV: results from the Western Cape Women's Health CoOp.

Alcohol and other drug use can negatively affect adherence to and retention in antiretroviral therapy (ART) among people living with HIV/AIDS. Yet, there are few brief interventions that reduce these behaviors among this population. This article presents the findings from a randomized field experiment that assessed the effects of a woman-focused intervention (the Women's Health CoOp [WHC]) on reducing alcohol and other drug use among vulnerable women in Cape Town, South Africa. The analyses were limited to 84 women living with HIV who reported drinking alcohol at baseline. Because of the small sample size, analyses were performed using an exact logistic regression procedure. At 12-month follow-up, women in the WHC arm were more likely to be abstinent from alcohol (odds ratio [OR] = 3.61; 95% confidence intervals [CI] = 1.23, 11.70; p = 0.016) and somewhat more likely to test negative for other drugs (OR = 3.07; 95% CI = 0.83, 12.31; p = 0.105), compared with women in the comparison arms. This study provides preliminary evidence of the efficacy of a brief, woman-focused intervention in reducing alcohol and other drug use among vulnerable women living with HIV and it has implications for HIV treatment.