Protocol for the Adolescent Menstrual Experiences and Health Cohort (AMEHC) Study in Khulna, Bangladesh: A Prospective cohort to quantify the influence of menstrual health on adolescent girls' health and education outcomes.

BACKGROUND: Menstrual health is essential for gender equity and the well-being of women and girls. Qualitative research has described the burden of poor menstrual health on health and education; however, these impacts have not been quantified, curtailing investment. The Adolescent Menstrual Experiences and Health Cohort (AMEHC) Study aims to describe menstrual health and its trajectories across adolescence, and quantify the relationships between menstrual health and girls' health and education in Khulna, Bangladesh. METHODS AND ANALYSIS: AMEHC is a prospective longitudinal cohort of 2016 adolescent girls recruited at the commencement of class 6 (secondary school, mean age=12) across 101 schools selected through a proportional random sampling approach. Each year, the cohort will be asked to complete a survey capturing (1) girls' menstrual health and experiences, (2) support for menstrual health, and (3) health and education outcomes. Survey questions were refined through qualitative research, cognitive interviews and pilot survey in the year preceding the cohort. Girls' guardians will be surveyed at baseline and wave 2 to capture their perspectives and household demographics. Annual assessments will capture schools' water, sanitation and hygiene, and support for menstruation and collect data on participants' education, including school attendance and performance (in maths, literacy). Cohort enrolment and baseline survey commenced in February 2023. Follow-up waves are scheduled for 2024, 2025 and 2026, with plans for extension. A nested subcohort will follow 406 post-menarche girls at 2-month intervals throughout 2023 (May, August, October) to describe changes across menstrual periods. This protocol outlines a priori hypotheses regarding the impacts of menstrual health to be tested through the cohort. ETHICS AND DISSEMINATION: AMEHC has ethical approval from the Alfred Hospital Ethics Committee (369/22) and BRAC James P Grant School of Public Health Institutional Review Board (IRB-06 July 22-024). Study materials and outputs will be available open access through peer-reviewed publication and study web pages.

Effectiveness and cost-effectiveness of a transdiagnostic intervention for alcohol misuse and psychological distress in humanitarian settings: study protocol for a randomised controlled trial in Uganda.

BACKGROUND: The war in South Sudan has displaced more than four million people, with Uganda hosting the largest number of South Sudanese refugees. Research in Uganda has shown elevated levels of alcohol misuse and psychological distress among these refugees. The World Health Organization (WHO) has developed a trans-diagnostic scalable psychological intervention called Problem Management Plus (PM +) to reduce psychological distress among populations exposed to adversities. Our study aims to evaluate the effectiveness and cost-effectiveness of the CHANGE intervention, which builds on PM + , to also address alcohol misuse through problem-solving therapy and selected behavioural strategies for dealing with alcohol use disorders. We hypothesise that the CHANGE intervention together with enhanced usual care (EUC) will be superior to EUC alone in increasing the percentage of days abstinent. METHODS: A parallel-arm individually randomised controlled trial will be conducted in the Rhino Camp and Imvepi settlements in Uganda. Five hundred adult male South Sudanese refugees with (i) elevated levels of alcohol use (between 8 and 20 on the Alcohol Use Disorder Identification Test [AUDIT]); and (ii) psychological distress (> 16 on the Kessler Psychological Distress Scale) will be randomly assigned 1:1 to EUC or CHANGE and EUC. CHANGE will be delivered by lay healthcare providers over 6 weeks. Outcomes will be assessed at 3 and 12 months post-randomisation. The primary outcome is the percentage of days abstinent, measured by the timeline follow-back measure at 3 months. Secondary outcomes include percentage of days abstinent at 12 months and alcohol misuse (measured by the AUDIT), psychological distress (i.e. depression, anxiety, posttraumatic stress disorder), functional disability, perpetration of intimate partner violence, and health economic indicators at 3 and 12 months. A mixed-methods process evaluation will investigate competency, dose, fidelity, feasibility, and acceptability. Primary analyses will be intention-to-treat. DISCUSSION: CHANGE aims to address alcohol misuse and psychological distress with male refugees in a humanitarian setting. If it is proven to be effective, it can help fill an important under-researched gap in humanitarian service delivery. TRIAL REGISTRATION: ISRCTN ISRCTN10360385. Registered on 30 January 2023.

Epidemiology of alcohol use and alcohol use disorders among people living with HIV on antiretroviral therapy in Northwest Tanzania: implications for ART adherence and case management.

Alcohol use disorders (AUD) among people living with HIV (PLHIV) are associated with poor health outcomes. This cross-sectional study examined current alcohol use and AUD among 300 PLHIV on ART at four HIV care centres in Northwest Tanzania. Participants' data were collected using questionnaires. Alcohol use was assessed using Alcohol Use Disorders Identification Test (AUDIT). Logistic regression was used to examine associations between each outcome (current drinking and AUD) and sociodemographic and clinical factors. Association between alcohol use and ART adherence was also studied. The median age of participants was 43 years (IQR 19-71) and 41.3% were male. Twenty-two (7.3%) participants failed to take ART at least once in the last seven days. The prevalence of current drinking was 29.3% (95% CI 24.2-34.8%) and that of AUD was 11.3% (8.2%-15.5%). Males had higher odds of alcohol use (OR 3.03, 95% CI 1.79-5.14) and AUD (3.89, 1.76-8.60). Alcohol use was associated with ART non-adherence (OR = 2.78, 1.10-7.04). There was a trend towards an association between AUD and non-adherence (OR = 2.91, 0.92-9.21). Alcohol use and AUD were common among PLHIV and showed evidence of associations with ART non-adherence. Screening patients for alcohol use and AUD in HIV clinics may increase ART adherence.

Health-related needs reported by adolescents living with HIV and receiving antiretroviral therapy in sub-Saharan Africa: a systematic literature review.

INTRODUCTION: Adolescents living with HIV (ALHIV) on antiretroviral therapy (ART) have specific health needs that can be challenging to deliver. Sub-Saharan Africa (SSA) is home to 84% of the global population of ALHIV, of whom about 59% receive ART. Several studies in SSA have demonstrated health service gaps due to lack of synchronized healthcare for ALHIV receiving ART. We conducted a systematic review of health-related needs among ALHIV on ART in SSA to inform decisions and policies on care. METHODS: We searched MEDLINE, Web of Science, EMBASE, PsycINFO, Cochrane library and grey literature for studies reporting health-related needs among ALHIV receiving ART in SSA, between January 2003 and May 2020. RESULTS AND DISCUSSION: Of the 2333 potentially eligible articles identified, 32 were eligible. Eligible studies were published between 2008 and 2019, in 11 countries: Zambia (7), Uganda (6), Tanzania (4), South Africa (4), Kenya (3), Ghana (2), Zimbabwe (2), Rwanda (1), Malawi (1), Botswana (1) and Democratic Republic of Congo (1). Seven categories of health needs among ALHIV were identified. In descending order of occurrence, these were: psychosocial needs (stigma reduction, disclosure and privacy support, and difficulty accepting diagnosis); dependency of care (need for family and provider support, and desire for autonomy); self-management needs (desire for better coping strategies, medication adherence support and reduced ART side effects); non-responsive health services (non-adolescent friendly facility services and non-compatible school system); need for food, financial and material support; inadequate information about HIV (desire for more knowledge to fight misinformation and misconception); and developmental and growth needs (desire to experience sex, parenthood and love). Ecological analysis identified different priority needs between ALHIV, their caregivers and healthcare providers, including psychosocial needs, financial challenges and non-responsive health services, respectively. CONCLUSIONS: To respond effectively to the health needs of ALHIV and improve ART adherence, interventions should focus on stigma reduction, disclosure challenges and innovative coping mechanisms for ART. Interventions that address the health needs of ALHIV from the perspective of carers and providers, such as financial support schemes and adolescent-friendly healthcare strategies, should supplement efforts to improve adolescent ART adherence outcomes.

Integration of a menstrual health intervention in a community-based sexual and reproductive health service for young people in Zimbabwe: a qualitative acceptability study.

BACKGROUND: Despite being fundamental to the health and well-being of women, menstrual health is often overlooked as a health priority and access to menstrual health education, products, and support is limited. Consequently, many young women are unprepared for menarche and face challenges in accessing menstrual health products and support and in managing menstruation in a healthy and dignified way. In this paper, we examine the acceptability of a comprehensive menstrual health and hygiene (MHH) intervention integrated within a community-based sexual and reproductive health (SRH) service for young people aged 16-24 years in Zimbabwe called CHIEDZA. METHODS: We conducted focus group discussions, that included participatory drawings, with CHIEDZA healthcare service providers (N = 3) and with young women who had attended CHIEDZA (N = 6) between June to August 2020. Translated transcripts were read for familiarisation and thematic analysis was used to explore acceptability. We applied Sekhon's thematic framework of acceptability that looks at seven key constructs (affective attitudes, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness, and self-efficacy). Data from FGDs and meeting minutes taken during the study time period were used to triangulate a comprehensive understanding of MHH intervention acceptability. RESULTS: The MHH intervention was acceptable to participants as it addressed the severe prevailing lack of access to menstrual health education, products, and support in the communities, and facilitated access to other SRH services on site. In addition to the constructs defined by Sekhon's thematic framework, acceptability was also informed by external contextual factors such as sociocultural norms and the economic environment. Providers highlighted the increased burden in their workload due to demand for MHH products, and how sociocultural beliefs around insertable menstrual products compromising virginity can negatively affect acceptability among young people and community members. CONCLUSIONS: MHH interventions are acceptable to young women in community-based settings in Zimbabwe as there is great unmet need for comprehensive MHH support. The integration of MHH in SRH services can serve as a facilitator to female engagement with SRH services. However, it is important to note that contextual external factors can affect the implementation and acceptability of integrated SRH and MHH services within communities. TRIAL REGISTRATION: Registry: Clinicaltrials.gov, Registration Number: NCT03719521 , Registration Date: October 25, 2018.

Effectiveness and costs associated with a lay counselor-delivered, brief problem-solving mental health intervention for adolescents in urban, low-income schools in India: 12-month outcomes of a randomized controlled trial.

BACKGROUND: Psychosocial interventions for adolescent mental health problems are effective, but evidence on their longer-term outcomes is scarce, especially in low-resource settings. We report on the 12-month sustained effectiveness and costs of scaling up a lay counselor-delivered, transdiagnostic problem-solving intervention for common adolescent mental health problems in low-income schools in New Delhi, India. METHODS AND FINDINGS: Participants in the original trial were 250 school-going adolescents (mean [M] age = 15.61 years, standard deviation [SD] = 1.68), including 174 (69.6%) who identified as male. Participants were recruited from 6 government schools over a period of 4 months (August 20 to December 14, 2018) and were selected on the basis of elevated mental health symptoms and distress/functional impairment. A 2-arm, randomized controlled trial design was used to examine the effectiveness of a lay counselor-delivered, problem-solving intervention (4 to 5 sessions over 3 weeks) with supporting printed booklets (intervention arm) in comparison with problem solving delivered via printed booklets alone (control arm), at the original endpoints of 6 and 12 weeks. The protocol was modified, as per the recommendation of the Trial Steering Committee, to include a post hoc extension of the follow-up period to 12 months. Primary outcomes were adolescent-reported psychosocial problems (Youth Top Problems [YTP]) and mental health symptoms (Strengths and Difficulties Questionnaire [SDQ] Total Difficulties scale). Other self-reported outcomes included SDQ subscales, perceived stress, well-being, and remission. The sustained effects of the intervention were estimated at the 12-month endpoint and over 12 months (the latter assumed a constant effect across 3 follow-up points) using a linear mixed model for repeated measures and involving complete case analysis. Sensitivity analyses examined the effect of missing data using multiple imputations. Costs were estimated for delivering the intervention during the trial and from modeling a scale-up scenario, using a retrospective ingredients approach. Out of the 250 original trial participants, 176 (70.4%) adolescents participated in the 12-month follow-up assessment. One adverse event was identified during follow-up and deemed unrelated to the intervention. Evidence was found for intervention effects on both SDQ Total Difficulties and YTP at 12 months (YTP: adjusted mean difference [AMD] = -0.75, 95% confidence interval [CI] = -1.47, -0.03, p = 0.04; SDQ Total Difficulties: AMD = -1.73, 95% CI = -3.47, 0.02, p = 0.05), with stronger effects over 12 months (YTP: AMD = -0.98, 95% CI = -1.51, -0.45, p < 0.001; SDQ Total Difficulties: AMD = -1.23, 95% CI = -2.37, -0.09; p = 0.03). There was also evidence for intervention effects on internalizing symptoms, impairment, perceived stress, and well-being over 12 months. The intervention effect was stable for most outcomes on sensitivity analyses adjusting for missing data; however, for SDQ Total Difficulties and impairment, the effect was slightly attenuated. The per-student cost of delivering the intervention during the trial was $3 United States dollars (USD; or $158 USD per case) and for scaling up the intervention in the modeled scenario was $4 USD (or $23 USD per case). The scaling up cost accounted for 0.4% of the per-student school budget in New Delhi. The main limitations of the study's methodology were the lack of sample size calculations powered for 12-month follow-up and the absence of cost-effectiveness analyses using the primary outcomes. CONCLUSIONS: In this study, we observed that a lay counselor-delivered, brief transdiagnostic problem-solving intervention had sustained effects on psychosocial problems and mental health symptoms over the 12-month follow-up period. Scaling up this resource-efficient intervention is an affordable policy goal for improving adolescents' access to mental health care in low-resource settings. The findings need to be interpreted with caution, as this study was a post hoc extension, and thus, the sample size calculations did not take into account the relatively high attrition rate observed during the long-term follow-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT03630471.

A lay-counsellor delivered brief psychological treatment for men with comorbid Alcohol Use Disorder and depression in primary care: Secondary analysis of data from a randomized controlled trial.

BACKGROUND: We investigated the feasibility, acceptability, safety, and preliminary effectiveness of the Counselling for Alcohol Problems (CAP) psychological intervention delivered by non-specialist health workers (NSHW) to participants with alcohol use disorder (AUD) and comorbid depression in primary care. METHODS: We used data from a single blind randomised controlled trial conducted in ten primary health care centres in Goa, India. Adult male harmful or dependent drinkers with or without depression were randomized (1:1) to receive either CAP & enhanced usual care (EUC) or EUC only. Process indicators such as the number of completed counselling sessions were assessed and compared between comorbid and non-comorbid participants. Remission from AUD and depression along with abstinence were measured at 3 and 12 months post randomisation. Analyses were on an intention-to-treat basis, employing multivariable regression analyses. RESULTS: 271 participants had symptoms of comorbid depression; 241 did not. Both groups completed a similar number of counselling sessions (adjusted Mean Difference 0.05, 95 %CI -0.24-0.34;p = 0.72). Among comorbid participants, CAP did not lead to more frequent adverse events compared to EUC only (adjusted Odds Ratio [aOR] 0.84, 0.43-1.64;p = 0.62), and there was no evidence for an effect of CAP on remission from AUD or depression at 3 months (aOR 1.51, 0.84-2.74;p = 0.17 and aOR 0.74, 0.43-1.27;p = 0.28) and 12 months follow-up, respectively (aOR 1.69, 0.96-3.01;p = 0.08 and aOR 1.08, 0.62-1.87;p = 0.79). CONCLUSIONS: Brief therapies like CAP can be safely delivered by NSHWs to patients with comorbid AUD and depression, but their effectiveness may be limited and requires further investigation.

Community-based HIV self-testing: a cluster-randomised trial of supply-side financial incentives and time-trend analysis of linkage to antiretroviral therapy in Zimbabwe.

BACKGROUND: HIV self-testing (HIVST) requires linkage to post-test services to maximise its benefits. We evaluated effect of supply-side incentivisation on linkage following community-based HIVST and evaluated time-trends in facility-based antiretroviral therapy (ART) initiations. METHODS: From August 2016 to August 2017 community-based distributors (CBDs) in 38 rural Zimbabwean communities distributed HIVST door-to-door in 19-25 day campaigns. Communities were allocated (1:1) using constrained randomisation to either one-off US$50 remuneration per CBD (non-incentive arm), or US$50 plus US$0.20 incentive per client visiting mobile-outreach services (conditional-incentive arm). The primary outcome, assessed by population survey 6 weeks later, was self-reported uptake of any clinic service, analysed with random-effects logistic regression. Separately, non-randomised difference-in-differences in monthly ART initiations were analysed for three time periods (6 months baseline; HIVST campaign; 3 months after) at public clinics with (40 clinics) and without (124 clinics) HIVST distribution in catchment area. FINDINGS: A total of 445 conditional-incentive CBDs distributed 39 205 HIVST kits (mean/CBD: 88; 95% CI: 85 to 92) and 447 non-incentive CBDs distributed 41 173 kits (mean/CBD: 93; 95% CI: 89 to 96). Survey participation was 7146/8566 (83.4%), with 3593 (50.3%) reporting self-testing including 1305 (18.3%) previously untested individuals. Use of clinic services post-HIVST was similar in conditional-incentive (1062/3698, 28.7%) and non-incentive (1075/3448, 31.2%) arms (adjusted risk ratio (aRR) 0.94, 95% CI: 0.86 to 1.03). Confirmatory testing by newly diagnosed/untreated HIVST+clients was, however, higher (conditional-incentive: 25/33, 75.8% vs non-incentive: 20/40, 50.0%: aRR: 1.59, 95% CI: 1.05 to 2.39). In total, 12 808 ART initiations occurred, with no baseline or postcampaign differences between initiation rates in HIVST versus non-HIVST clinics, but initiation rates increased from 7.31 to 9.59 initiations per month in HIVST clinics during distribution, aRR: 1.27, 95% CI 1.17 to 1.39. CONCLUSIONS: Community-based HIVST campaigns achieved high testing uptake, temporally associated with increased demand for ART. Small supply-side incentives did not affect general clinic usage but may have increased confirmatory testing for newly diagnosed HIVST positive participants. TRIAL REGISTRATION NUMBER: PACTR201607001701788.

Effectiveness and cost-effectiveness of integrating the management of depression into routine HIV Care in Uganda (the HIV + D trial): A protocol for a cluster-randomised trial.

BACKGROUND: An estimated 8-30 % of people living with HIV (PLWH) have depressive disorders (DD) in sub-Saharan Africa. Of these, the majority are untreated in most of HIV care services. There is evidence from low- and middle- income countries of the effectiveness of both psychological treatments and antidepressant medication for the treatment of DD among PLWH, but no evidence on how these can be integrated into routine HIV care. This protocol describes a cluster-randomised trial to evaluate the effectiveness and cost-effectiveness of the HIV + D model for the integration of a collaborative stepped care intervention for DD into routine HIV care, which we have developed and piloted in Uganda. METHODS: Forty public health care facilities that provide HIV care in Kalungu, Masaka and Wakiso Districts will be randomly selected to participate in the trial. Each facility will recruit 10-30 eligible PLWH with DD and the total sample size will be 1200. The clusters will be randomised 1:1 to receive Enhanced Usual Care alone (EUC, i.e. HIV clinicians trained in Mental Health Gap Action Programme including guidelines on when and where to refer patients for psychiatric care) or EUC plus HIV + D (psychoeducation, Behavioural Activation, antidepressant medication and referral to a supervising mental health worker, delivered in a collaborative care stepwise approach). Eligibility criteria are PLWH attending the clinic, aged ≥ 18 years who screen positive on a depression screening questionnaire (Patient Health Questionnaire, PHQ-9 ≥ 10). The primary outcome is the mean depressive disorder symptom severity scores (assessed using the PHQ-9) at 3 months' post-randomisation, with secondary mental health, disability, HIV and economic outcomes measured at 3 and 12 months. The cost-effectiveness of EUC with HIV + D will be assessed from both the health system and the societal perspectives by collecting health system, patient and productivity costs and mean DD severity scores at 3 months, additional to health and non-health related quality of life measures (EQ-5D-5 L and OxCAP-MH). DISCUSSION: The study findings will inform policy makers and practitioners on the cost-effectiveness of a stepped care approach to integrate depression management in routine care for PLWH in low-resource settings. TRIAL REGISTRATION: ISRCTN, ISRCTN86760765. Registered 07 September 2017, https://doi.org/10.1186/ISRCTN86760765 .

Assessing the effectiveness of a comprehensive menstrual health intervention program in Ugandan schools (MENISCUS): process evaluation of a pilot intervention study.

BACKGROUND: Poor menstrual health and hygiene (MHH) is a globally recognised public health challenge. A pilot study of an MHH intervention was conducted in two secondary schools in Entebbe, Uganda, over 9 months. The intervention included five components delivered by the implementing partner (WoMena Uganda) and the research team: (i) training teachers to implement government guidelines for puberty education, (ii) a drama skit to reduce stigma about menstruation, (iii) training in use of a menstrual kit (including re-usable pads), (iv) guidance on pain relief methods including provision of analgesics and (v) improvements to school water, sanitation and hygiene (WASH) facilities. The aim of the process evaluation was to examine implementation, context and possible causal pathways. METHODS: We collected information on fidelity, dose, reach, acceptability, context and mechanisms of impact using (i) quantitative survey data collected from female and male students in year 2 of secondary school (ages 13-21; 450 at the baseline and 369 at endline); (ii) qualitative data from 40 in-depth interviews with parents, teachers and female students, and four focus group discussions with students, stratified by gender; (iii) data from unannounced visits checking on WASH facilities throughout the study; and (iv) routine data collected as part of the implementation. Quantitative data were used primarily to assess fidelity, dose and reach. Qualitative data were used primarily to assess acceptability, context and possible mechanisms. RESULTS: Both schools received all intervention elements that were delivered by the research team and implementing partner. The drama skit, menstrual kit and pain management intervention components were delivered with fidelity. Intervention components that relied on school ownership (puberty education training and WASH improvements) were not fully delivered. Overall, the intervention was acceptable to participants. Multilevel contextual factors including schools' social and physical environment, and family, cultural and social factors influenced the acceptability of the intervention in the school setting. The intervention components reinforced one another, as suggested in our theoretical framework. CONCLUSION: The intervention was feasible to deliver and acceptable to the schools and students. We propose a full-scale cluster-randomised trial to evaluate the intervention, adding a school-based MHH leadership group to address issues with school ownership. TRIAL REGISTRATION: ClinicalTrials.gov NCT04064736. Registered August 22, 2019, retrospectively registered.

Context of Violence in Adolescence Cohort (CoVAC) study: protocol for a mixed methods longitudinal study in Uganda.

BACKGROUND: Violence exposure in adolescence is associated with a range of poor health and social outcomes, including both the perpetration and experience of violence in later intimate relationships. However, there is little longitudinal evidence on how both individual and contextual characteristics encourage or interrupt these associations. We designed the Contexts of Violence in Adolescence Cohort study (CoVAC) to provide evidence on these pathways for Ugandan adolescents, with the aim of providing information to improve the design of violence prevention interventions for adolescents and young adults. METHODS: CoVAC is a mixed-methods prospective cohort study with three parallel strands. Between 2014 and 2022, the study comprises three waves of quantitative survey data collection; qualitative data from five time points; and a series of workshops to facilitate direct use of emerging findings by intervention developers at Uganda-based NGO Raising Voices in their ongoing work to prevent violence. 3431 adolescents participated in a survey in 2014 when the majority were aged 11-14 years, and agreed to be re-contacted for a Wave 2 survey in 2018 (aged about 15-18 years); and again in 2021 (aged 18-21 years). 36 young people from Wave 1 survey sample will be invited to participate in longitudinal qualitative data collection. Adolescents aged 18 years and over will provide informed consent; for those under age 18 years, adolescents will be invited to assent, except in cases where caregivers, following notification, have opted not to consent to their adolescent's participation. Quantitative and qualitative data will be analysed iteratively, and triangulation will be used to confirm, clarify and deepen our interpretation of findings. We will hold regular structured meetings so that emerging findings can be integrated into intervention development. DISCUSSION: This will be the first longitudinal study on the aetiology of violence over adolescence in sub-Saharan Africa which will enable examination of pathways using mixed methods at multiple time points. Quantitative mediation analysis, and annual qualitative fieldwork will provide detailed insights into how adolescents' violence-related experiences, perspectives and practices relate to their social contexts and how these change over time. Results will feed directly into intervention development to reduce violence and harmful sequelae. TRIAL REGISTRATION: This study is a long-term follow up of participants in the Good Schools Study (NCT01678846, clinicaltrials.gov). This protocol is for cohort follow-up only; we have a separate protocol paper describing an evaluation of the long-term effects of the Good School Toolkit (In preparation).

Comparing Alcohol Use Disorders Identification Test (AUDIT) with Timeline Follow Back (TLFB), DSM-5 and Phosphatidylethanol (PEth) for the assessment of alcohol misuse among young people in Ugandan fishing communities.

BACKGROUND: Validated tools for assessing alcohol use among young people in low-income countries are needed to estimate prevalence and evaluate alcohol-reduction interventions. We validated Alcohol Use Disorders Identification Test (AUDIT) against Timeline Follow Back (TLFB), Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and phosphatidylethanol (PEth); and the 30-day-AUDIT against the 12-months-AUDIT among young Ugandans. METHODS: In 2018, we collected retrospective data on 30-day and 12-month AUDIT, TLFB and DSM-5 in a cross-sectional study of 15-24 year old residents of Ugandan fishing communities. AUDIT was administered by Audio Computer Assisted Self-Interviewing (ACASI) and DSM-5 and TLFB by psychiatric nurses. We determined PEth16:0/18:1 levels from dried blood spots using liquid chromatography tandem-mass spectrometry (heavy usage, ≥210 ng/mL) and calculated sensitivity and specificity of AUDIT against the other measures. RESULTS: Among 1281 participants (52.7% male, mean age 20 years), half (n = 659; 51.4%) reported ever drinking alcohol, 19.4% had 12-month-AUDIT ≥ 8 (21.5% men; 17.0% women), and 24.2% had 30-day-AUDIT ≥ 8 (29.0% men; 18.9% women). Twenty percent of participants had detectable PEth with 55 (4.3%) classified as heavy drinkers; 50.7% reported ≥ 2 symptoms on DSM-5 and 6.3% reported binge drinking in the previous month based on TLFB (8.9% men, 3.5% women). The 30-day-AUDIT ≥ 8 had sensitivity 86.7%, 95%CI: 81.8%-90.7% and specificity 90.9%, 95%CI:89.0%-92.6% versus 12-month-AUDIT ≥ 8. Both 30-day and 12-month-AUDIT ≥ 8 were sensitive and specific markers of heavy drinking by PEth (12-month-AUDIT sensitivity = 80.0%; 95%CI:67.0%-89.6%; specificity = 83.3%; 95%CI:81.1%-85.3%). The 30-day-AUDIT was a sensitive and specific marker of binge drinking based on TLFB (sensitivity = 82.7%; 95%CI:72.7%-90.2%, specificity = 79.8%; 95%CI:77.4%-82.1%); 12-month-AUDIT had lower sensitivity. Both 30-day and 12-month AUDIT ≥ 8 were highly specific but insensitive markers of having DSM-5 ≥ 2 symptoms. CONCLUSION: Among young people in Uganda, ACASI-administered 30-day and 12-month-AUDIT have good diagnostic properties compared to PEth, DSM-5 and TLFB. Self-reported AUDIT provides a quick and valid means of assessing alcohol misuse in these communities.

Effects of parenting classes and economic strengthening for caregivers on the cognition of HIV-exposed infants: a pragmatic cluster randomised controlled trial in rural Zimbabwe.

INTRODUCTION: HIV-exposed children show signs of developmental delay. We assessed the impact of a pragmatic multicomponent intervention for caregivers of HIV-exposed children aged 0-2 years in Zimbabwe. METHODS: We conducted a cluster-randomised trial from 2016 to 2018. Clusters were catchments surrounding clinics, allocated (1:1) to either National HIV guidelines standard of care or standard care plus an 18-session group intervention comprising i) early childhood stimulation (ECS) and parenting training with home visits to reinforce skills and retention in HIV care; ii) economic strengthening. Primary outcomes measured 12 months after baseline (4.5 months postintervention completion) included: i) global child development measured using the Mullen early learning composite score; ii) retention in HIV care. Analysis used mixed effects regression to account for clustering and adjusted minimally for baseline prognostic factors and was by intention to treat. RESULTS: Thirty clusters, 15 in each arm, were randomised. 574 dyads were recruited with 89.5% retained at follow-up. Ninety one of 281 (32.4%) were recorded as having received the complete intervention package, with 161/281 (57.3%) attending ≥14 ECS sessions. There was no evidence of an intervention effect on global child development (intervention mean 88.1 vs standard of care mean 87.6; adjusted mean difference=0.06; 95% CI -2.68 to 2.80; p=0.97) or infant retention in care (proportion of children who had missed their most recent HIV test: intervention 21.8% vs standard of care 16.9%, p=0.18). There was weak evidence that the proportion of caregivers with parental stress was reduced in the intervention arm (adjusted OR (aOR)=0.69; 95% CI 0.45 to 1.05; p=0.08) and stronger evidence that parental distress specifically was reduced (intervention arm 17.4% vs standard of care 29.1% scoring above the cut-off; aOR=0.56; 95% CI 0.35 to 0.89; p=0.01). CONCLUSION: This multicomponent intervention had no impact on child development outcomes within 4.5 months of completion, but had an impact on parental distress. Maternal mental health remains a high priority. TRIAL REGISTRATION NUMBER: PACTR201701001387209.

Evaluating the effectiveness and cost-effectiveness of health facility-based and community-based index-linked HIV testing strategies for children: protocol for the B-GAP study in Zimbabwe.

INTRODUCTION: The number of new paediatric infections per year has declined in sub-Saharan Africa due to prevention-of-mother-to-child HIV transmission programmes; many children and adolescents living with HIV remain undiagnosed. In this protocol paper, we describe the methodology for evaluating an index-linked HIV testing approach for children aged 2-18 years in health facility and community settings in Zimbabwe. METHODS AND ANALYSIS: Individuals attending for HIV care at selected primary healthcare clinics (PHCs) will be asked if they have any children aged 2-18 years in their households who have not been tested for HIV. Three options for HIV testing for these children will be offered: testing at the PHC; home-based testing performed by community workers; or an oral mucosal HIV test given to the caregiver to test the children at home. All eligible children will be followed-up to ascertain whether HIV testing occurred. For those who did not test, reasons will be determined, and for those who tested, the HIV test result will be recorded. The primary outcome will be uptake of HIV testing. The secondary outcomes will be preferred HIV testing method, HIV yield, prevalence and proportion of those testing positive linking to care and having an undetectable viral load at 12 months. HIV test results will be stratified by sex and age group, and factors associated with uptake of HIV testing and choice of HIV testing method will be investigated. ETHICS AND DISSEMINATION: Ethical approval for this study was granted by the Medical Research Council of Zimbabwe, the London School of Hygiene and Tropical Medicine and the Institutional Review Board of the Biomedical Research and Training Institute. Study results will be presented at national policy meetings and national and international research conferences. Results will also be published in international peer-reviewed scientific journals and disseminated to study communities at the end of study.

Feasibility, acceptability and cost-effectiveness of a brief, lay counsellor-delivered psychological treatment for men with alcohol dependence in primary care: an exploratory randomized controlled trial.

AIMS: To examine the feasibility, acceptability and preliminary cost-effectiveness of a lay counsellor delivered psychological treatment for men with alcohol dependence in primary care. DESIGN: Single-blind individually randomized trial comparing counselling for alcohol problems (CAP) plus enhanced usual care (EUC) versus EUC only. SETTING: Ten primary health centres in Goa, India. PARTICIPANTS: Men (n = 135) scoring ≥ 20 on the Alcohol Use Disorder Identification Test (AUDIT). Sixty-six participants were randomized to EUC and 69 to CAP + EUC. INTERVENTIONS: CAP, a lay counsellor-delivered psychological treatment for harmful drinking, with referral to de-addiction centre for medically assisted detoxification. EUC comprised consultation with physician, providing screening results and referral to a de-addiction centre. MEASUREMENTS: Baseline socio-demographic data, readiness to change and perceived usefulness of counselling. Acceptability and feasibility process indicators such as data on screening and therapy. Outcomes were measured at 3 and 12 months post-randomization and included remission, mean daily alcohol consumed, percentage of days abstinent (PDA), percentage of days of heavy drinking (PDHD), recovery, uptake of detoxification services, impacts of alcohol dependence, resource use and costs. FINDINGS: Participants in the CAP + EUC arm had more numerically but not statistically significantly favourable outcomes compared with those in the EUC arm for (a) remission at 3 months [adjusted odds ratio (aOR) = 1.95, 95% confidence interval (CI) = 0.74-5.15] and 12 months (aOR = 1.90, 95% CI = 0.72-5.00), (b) proportion of non-drinkers at 3 months (aOR = 1.26; 95% CI = 0.58-2.75) and 12 months (aOR = 1.25; 95% CI = 0.58-2.64) and (c) ethanol consumption among drinkers at 3 months (count ratio = 0.91; 95% CI = 0.58-1.45) and 12 months (count ratio = 1.06; 95% CI = 0.73-1.54). There was no statistically significant evidence of a difference in the occurrence of serious adverse events between the two arms. From a societal perspective, there was a 53% chance of CAP + EUC being cost-effective in achieving remission at 12 months at the willingness-to-pay threshold of $415. CONCLUSIONS: Lay counsellor-delivered psychological treatment for men with alcohol dependence (AD) in primary care may be effective in managing AD in low- and middle-income countries. A definitive trial of the intervention is warranted.

Delivering the Thinking Healthy Programme for perinatal depression through peers: an individually randomised controlled trial in India.

BACKGROUND: The Thinking Healthy Programme (THP) is a psychological intervention recommended for the treatment of perinatal depression. However, efforts to integrate the intervention at scale into the routines of community health workers who delivered the THP when it was first evaluated were compromised by the competing responsibilities of community health workers. We aimed to assess the effectiveness and cost-effectiveness of THP peer-delivered (THPP) in Goa, India. METHODS: In this single-blind, individually randomised controlled trial, we recruited pregnant women aged 18 years or older who scored at least 10 on the Patient Health Questionnaire-9 (PHQ-9) from antenatal clinics in Goa. Participants were randomly allocated (1:1) to receive enhanced usual care (EUC; so-called because, in India, perinatal depression is not typically treated) only (control group) or THPP in addition to EUC (intervention group) in randomly sized blocks that were stratified by area of residence (urban or rural). Group allocations were concealed from participants and researchers before assignments were made by use of sequentially numbered opaque envelopes. The primary outcomes were the severity of depressive symptoms (assessed by PHQ-9 score) and the prevalence of remission (defined as a PHQ-9 score of less than 5) in participants with available data 6 months after childbirth, which was assessed by researchers who were masked to treatment allocations. We analysed outcomes by intention to treat, adjusting for covariates that were defined a priori or that showed imbalance at baseline. The trial is registered with ClinicalTrials.gov, number NCT02104232. FINDINGS: Between Oct 24, 2014, and June 24, 2016, we assessed 118 260 women for their eligibility for screening, of whom 111 851 (94·6%) women were ineligible. 6409 (5·4%) women were eligible for screening and 6369 (99·4%) of these women consented to be screened with the PHQ-9 (40 women did not consent), of whom 333 (5·2%) screened positive for depression (defined as a PHQ-9 score of at least 10). We enrolled 280 (84·1%) women with perinatal depression; 140 women were assigned to the THPP and EUC group and 140 women to the EUC only group. The final treatment was given on May 27, 2017. The final 6-month outcome assessment was completed on June 9, 2017. At 6 months after birth, 122 (87%) women in the THPP and EUC group and 129 (92%) women in the EUC only group were assessed for the primary outcome. There was a higher prevalence of remission at 6 months after birth in the THPP and EUC group compared with the EUC only group (89 [73%] women in the intervention group vs 77 [60%] women in the control group; prevalence ratio 1·21, 95% CI 1·01 to 1·45; p=0·04), but there was no evidence of a difference in symptom severity between the groups (mean PHQ-9 score 3·47 [SD 4·49] in the intervention group vs 4·48 [5·11] in the control group; standardised mean difference -0·18, 95% CI -0·43 to 0·07; p=0·16). There was no evidence of significant differences in serious adverse events between the groups. INTERPRETATION: THPP had a moderate effect on remission from perinatal depression over the 6-month postnatal period. THPP is relatively cheap to deliver and is cost-saving through reduced health-care, time and productivity costs. FUNDING: National Institute of Mental Health (USA).

Delivering the Thinking Healthy Programme for perinatal depression through volunteer peers: a cluster randomised controlled trial in Pakistan.

BACKGROUND: The Thinking Healthy Programme (THP), which is endorsed by WHO, is an evidence-based intervention for perinatal depression. We adapted THP for delivery by volunteer peers (laywomen from the community) to address the human resource needs in bridging the treatment gap, and we aimed to assess its effectiveness and cost-effectiveness in Rawalpindi, Pakistan. METHODS: In this cluster randomised controlled trial, we randomly assigned 40 village clusters (1:1) to provide either THP peer-delivered (THPP) and enhanced usual care (EUC; intervention group) or EUC only (control group) to the participants within clusters. These villages were randomly selected from eligible villages by an independent researcher. The participants were pregnant women aged 18 years or older who had scored at least 10 on the Patient Health Questionnaire-9 (PHQ-9), who we recruited from households within communities in Rawalpindi, Pakistan. The research teams who were responsible for recruiting trial participants were masked to treatment allocations. Participants attended follow-up visits at 3 and 6 months after childbirth. The primary outcomes were the severity of depressive symptoms (assessed by PHQ-9 score) and the prevalence of remission (defined as a PHQ-9 score of less than 5) in participants with available data 6 months after childbirth, which was assessed by researchers who were masked to treatment allocations. We analysed outcomes by intention to treat, adjusting for covariates that were defined a priori or that showed imbalance at baseline. The trial was registered with ClinicalTrials.gov, number NCT02111915. FINDINGS: Between April 15 and July 30, 2014, we randomly selected 40 of 46 eligible village clusters for assessment, as per sample size calculations. Between Oct 15, 2014, and Feb 25, 2016, we identified and screened 971 women from 20 village clusters that had been randomly assigned to the THPP and EUC group and 939 women from 20 village clusters that had been randomly assigned to the EUC only group. In the intervention group, 79 women were ineligible for inclusion, 11 women refused screening, 597 women screened negative on the PHQ-9, and one woman did not consent to participate. In the control group, 75 women were ineligible for inclusion, 14 women refused screening, 562 women screened negative on the PHQ-9, and one woman did not consent to participate. We enrolled 283 (29%) women in the intervention group and 287 (31%) women in the control group. At 6 months after childbirth, 227 (80%) women in the THPP and EUC group and 226 (79%) women in the EUC only group were assessed for the primary outcome. The severity of depression (assessed by PHQ-9 scores; standardised mean difference -0·13, 95% CI -0·31 to 0·06; p=0·07) and prevalence of remission (49% in the intervention group vs 45% in the control group; prevalence ratio 1·12, 95% CI 0·95 to 1·29; p=0·14) did not significantly differ between the groups 6 months after childbirth. There was no evidence of significant differences in serious adverse events between the groups. INTERPRETATION: THPP had no effect on symptom severity or remission from perinatal depression at 6 months after childbirth, but we found that it was beneficial on some other metrics of severity and disability and that it was cost-effective. THPP could be a step towards use of an unused human resource to address the treatment gap in perinatal depression. FUNDING: National Institute of Mental Health (USA).

The effectiveness and cost-effectiveness of community-based lay distribution of HIV self-tests in increasing uptake of HIV testing among adults in rural Malawi and rural and peri-urban Zambia: protocol for STAR (self-testing for Africa) cluster randomized evaluations.

BACKGROUND: Knowledge of HIV status remains below target in sub-Saharan Africa, especially among men and adolescents. HIV self-testing (HIVST) is a novel approach that enables unique distribution strategies, with potential to be highly decentralised and to provide complementary coverage to facility-based testing approaches. However, substantial gaps in evidence remain on the effectiveness and cost-effectiveness of HIVST, particularly in rural settings, and on approaches to facilitate linkage to confirmatory HIV testing, prevention, and treatment services. This protocol describes two cluster-randomized trials (CRT) included within the UNITAID/PSI HIV Self-Testing Africa (STAR) project. METHODS: Two independent CRTs were designed around existing reproductive health programmes in rural Malawi and rural/peri-urban Zambia. Common features include use of constrained randomisation to allocate health clinic catchment areas to either standard HIV testing (SOC) or SOC plus community-based distribution of OraQuick HIV Self Tests (Bethlehem, PA USA, assembled in Thailand) by trained lay distributors selected by the community. Community-based distribution agents will be trained (3-day curriculum) to provide brief demonstration of kit use and interpretation, information and encouragement to access follow up services, and management of social harm. The primary outcome of both CRTs is the proportion of the population aged 16 years and older who tested for HIV within the 12-month intervention period. Secondary outcomes in both trials include lifetime HIV testing, antiretroviral therapy (ART) initiation and ART use. Circumcision status among males will be a secondary outcome in Zambia and clinic-level demand for ART will be a secondary outcome in Malawi. Outcomes will be measured using cross-sectional household surveys, and routine data extraction from participating clinics. Costing studies will be used to evaluate the cost-effectiveness of the intervention arm. Qualitative research will be used to guide distribution and explore reasons for testing and linkage to onward care. DISCUSSION: The STAR-Malawi and STAR-Zambia trials will provide rigorous evidence of whether community-based lay HIVST distribution is an effective and cost-effective approach to increasing coverage of HIV testing and demand for follow-on HIV services in rural and peri-urban communities in sub-Saharan Africa. TRIAL REGISTRATION: Clinicaltrials.gov, Malawi: NCT02718274 , 18 March 2016; Zambia: NCT02793804 , 3 June 2016. Protocol date: 21 February 2018.