Understanding effective post-test linkage strategies for HIV prevention and care: a scoping review.

INTRODUCTION: Following HIV testing services (HTS), the World Health Organization recommends prompt linkage to prevention and treatment. Scale-up of effective linkage strategies is essential to achieving the global 95-95-95 goals for maintaining low HIV incidence by 2030 and reducing HIV-related morbidity and mortality. Whereas linkage to care including same-day antiretroviral therapy (ART) initiation for all people with HIV is now routinely implemented in testing programmes, linkage to HIV prevention interventions including behavioural or biomedical strategies, for HIV-negative individuals remains sub-optimal. This review aims to evaluate effective post-HTS linkage strategies for HIV overall, and highlight gaps specifically in linkage to prevention. METHODS: Using the five-step Arksey and O'Malley framework, we conducted a scoping review searching existing published and grey literature. We searched PubMed, Cochrane Library, CINAHL, Web of Science and EMBASE databases for English-language studies published between 1 January 2010 and 30 November 2023. Linkage interventions included as streamlined interventions-involving same-day HIV testing, ART initiation and point-of-care CD4 cell count/viral load, case management-involving linkage coordinators developing personalized HIV care and risk reduction plans, incentives-financial and non-financial, partner services-including contact tracing, virtual-like social media, quality improvement-like use of score cards, and peer-based interventions. Outcomes of interest were linkage to any form of HIV prevention and/or care including ART initiation. RESULTS: Of 2358 articles screened, 66 research studies met the inclusion criteria. Only nine linkage to prevention studies were identified (n = 9/66, 14%)-involving pre-exposure prophylaxis, voluntary medical male circumcision, sexually transmitted infection and cervical cancer screening. Linkage to care studies (n = 57/66, 86%) focused on streamlined interventions in the general population and on case management among key populations. DISCUSSION: Despite a wide range of HIV prevention interventions available, there was a dearth of literature on HIV prevention programmes and on the use of messaging on treatment as prevention strategy. Linkage to care studies were comparatively numerous except those evaluating virtual interventions, incentives and quality improvement. CONCLUSIONS: The findings give insights into linkage strategies but more understanding of how to provide these effectively for maximum prevention impact is needed.

Determining reinfection rates by hepatitis C testing interval among key populations: A systematic review and meta-analysis.

BACKGROUND & AIMS: Detecting hepatitis C virus (HCV) reinfection among key populations helps prevent ongoing transmission. This systematic review aims to determine the association between different testing intervals during post-SVR follow-up on the detection of HCV reinfection among highest risk populations. METHODS: We searched electronic databases between January 2014 and February 2023 for studies that tested individuals at risk for HCV reinfection at discrete testing intervals and reported HCV reinfection incidence among key populations. Pooled estimates of reinfection incidence were calculated by population and testing frequency using random-effects meta-analysis. RESULTS: Forty-one single-armed observational studies (9453 individuals) were included. Thirty-eight studies (8931 individuals) reported HCV reinfection incidence rate and were included in meta-analyses. The overall pooled estimate of HCV reinfection incidence rate was 4.13 per 100 per person-years (py) (95% confidence interval [CI]: 3.45-4.81). The pooled incidence estimate among people who inject drugs (PWID) was 2.84 per 100 py (95% CI: 2.19-3.50), among men who have sex with men (MSM) 7.37 per 100 py (95% CI: 5.09-9.65) and among people in custodial settings 7.23 per 100 py (95% CI: 2.13-16.59). The pooled incidence estimate for studies reporting a testing interval of ≤6 months (4.26 per 100 py; 95% CI: 2.86-5.65) was higher than studies reporting testing intervals >6 months (5.19 per 100 py; 95% CI: 3.92-6.46). CONCLUSIONS: HCV reinfection incidence was highest in studies of MSM and did not appear to change with retesting interval. Shorter testing intervals are likely to identify more reinfections, help prevent onward transmission where treatment is available and enable progress towards global HCV elimination, but additional comparative studies are required.

Immediate treatment for recent hepatitis C infection in people with high-risk behaviors: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) are almost exclusively approved for the treatment of chronic HCV. This poses a significant barrier to the treatment of recently acquired HCV because of the limited access to DAAs. This review seeks to address this issue by synthesizing evidence of the benefits and harms of immediate treatment after the detection of recently acquired HCV in people at higher risk of infection. APPROACH AND RESULTS: A systematic review and meta-analysis were conducted reporting on populations with recently acquired HCV at higher risk of infection. Studies were included if they assessed standard duration DAA treatment regimens and reported on the benefits and harms of immediate treatment (within one year of diagnosis). Outcomes included sustained virological response at 12 weeks post-treatment (SVR12), incidence, treatment initiation and adherence, overtreatment, engagement in care, and adverse events. Eight cohort studies, 3 open-label trials, and 1 case series study were included, reporting on 2085 participants with recently acquired HCV infection. No studies included a comparison group. Eight studies assessed DAA treatment in either men who have sex with men or men who have sex with men with HIV, 2 studies assessed treatment in people who inject drugs, and 2 among people living with HIV. Immediate treatment of HCV was associated with a pooled SVR12 of 95.9% (95% CI, 92.6%-99.3%). Three studies reported on hepatitis C incidence, where most participants were treated in the chronic phase of infection. A treatment completion rate of 100% was reported in 2 studies, and only 1 serious adverse event was described. CONCLUSIONS: High rates of cure were achieved with the treatment of recently acquired hepatitis C in people at higher risk of infection. Serious adverse events were rare, highlighting individual benefits consistent with the treatment of chronic hepatitis C. The impact of immediate treatment on HCV incidence requires further evaluation.

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.

Evaluation of cultural competency in a South African cluster randomised controlled trial: lessons learned for trial reporting standards.

BACKGROUND: Failure to consider relevant cultural, ethnic and diversity parameters (and the intersection between these parameters) during trial protocol development and trial conduct may negatively impact recruitment, intervention development and delivery, and participant adherence and retention, potentially reducing overall internal validity. This case study aimed to evaluate the utility and comparability between the 9-item Gibbs Framework to measure cultural competency and the GRIPP-2(Short Form (SF)) 5-point checklist to assess patient and public involvement in the context of a complex clinical trial conducted in an African setting. METHODS: We identified and collated all relevant publications, source and procedural data related to the trial and integrated the documents into a dynamic trial timeline. Two independent investigators applied and scored the Gibbs Framework and the GRIPP-2(SF) checklist to the four publications arising from the trial, noting functionality and comparability between tools. Where cultural competency was not met, a third investigator screened all procedural and source data and identified if cultural competency had been achieved but not reported in the publications, or if the trial had not met appropriate cultural competency based on the documentation. RESULTS: Application of the Gibbs Framework found that the trial scored '2' for seven of the nine Gibbs items, indicating full cultural competency for those questions. The Framework indicated that the trial research question was not driven by the articulated needs of patients, and neither were patients, caregivers and clinical providers involved in the development of the intervention. Comparability with the GRIPP-2(SF) checklist showed that the Gibbs performed better on evaluation of partnerships with the community, identification of culturally competent data sources and target populations, and appointment of trial staff in an inclusive manner. CONCLUSIONS: Comprehensive evaluation of the trial's cultural competency required scrutiny of both published manuscripts and source and procedural data, suggesting that there is a gap in current trial reporting standards with respect to cultural competence. TRIAL REGISTRATION: PACTR201610001825403. Registered on 17 October 2016.

Whole-of-community interventions that address alcohol-related harms: protocol for a scoping review.

INTRODUCTION: Alcohol-related harm is a rising global concern particularly in low-income and middle-income countries where alcohol use fuels the high rates of violence, road traffic accidents and is a risk factor for communicable diseases such as HIV/AIDS and tuberculosis. Existing evidence to address alcohol-related harm recommends the use of intersectoral approaches, however, previous efforts have largely focused on addressing individual behaviour with limited attention to whole-of-community approaches. Whole-of-community approaches are defined as intersectoral interventions that are systematically coordinated and implemented across the whole community. The objective of this scoping review is to synthesise the existing literature on multisectoral, whole-of-community interventions which have been used to modify or prevent alcohol-related harms. METHODS AND ANALYSIS: This scoping review will follow the six-step approach that involves; (1) identifying the research question, (2) identifying relevant studies, (3) selecting studies, (4) charting the data, (5) collating, summarising and reporting the results and (6) expert consultation. Published literature from 2010 to 2021 will be accessed through PubMed, Web of Science, CINAHL Plus and Scopus databases. Search terms will focus on the concepts of 'interventions', 'community-based', 'harm reduction' and 'alcohol'. There will be no restrictions on the type of study methodology or country of origin. Title and abstract followed by full-text screening will be conducted by two reviewers to identify relevant articles based on the inclusion and exclusion criteria. Data from selected articles will be extracted and charted in Excel software. Findings will be analysed qualitatively and presented using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis: Extension for Scoping Review. ETHICS AND DISSEMINATION: This review makes use of published and publicly available data and no ethics approval is required. The results from this study will be disseminated via publication in peer-reviewed journals and presentations at relevant academic research fora and conferences.

SARS-CoV-2 transmission in schools: An updated living systematic review (version 2; November 2020).

BACKGROUND: Better understanding of SARS-CoV-2 transmission risks is needed to support decision-making around mitigation measures for COVID-19 in schools. METHODS: We updated a living systematic review and meta-analysis to investigate the extent of SARS-CoV-2 transmission in schools. In this update we modified our inclusion criteria to include: 1) cohort studies; 2) cross-sectional studies that investigated and cross-assessed SARS-COV-2 positivity rates in schools and communities; and 3) pre-post studies. We performed risk of bias evaluation for all included studies using the Newcastle-Ottawa Scale (NOS). RESULTS: 6270 articles were retrieved and six new studies were added in this update. In total from the two updates and using the new inclusion criteria, we identified 11 cohort studies (1st update: n = 5; 2nd update: n = 6) and one cross-sectional study (1st update: n = 1; 2nd update: n = 0). We performed a meta-analysis on nine of the 11 cohort studies investigating IAR in schools. Nine cohort studies reported a total of 91 student and 52 staff index cases that exposed 5698 contacts with 101 secondary infections (overall infection attack rate (IAR) = 1.45%, 95% CI = 0.31%-3.26%). IARs for students and school staff were 1.66% (95% CI = 0.08%-4.78%) and 1.18% (95% CI = 0.00%-4.43%) respectively. The risk of bias was found to be high for most studies identified, limiting the confidence in results. CONCLUSIONS: There is limited high-quality evidence available to quantify the extent of SARS-CoV-2 transmission in schools or to compare it to community transmission. Emerging evidence suggests the overall IAR and SARS-CoV-2 positivity rate in school settings are low. Higher IAR were found in students, compared to staff. NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. This is the second version of the original article published on 23 December 2020 (J Glob Health 2020;11:021104), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

The Use of Magnetic Resonance Imaging Techniques in Assessing the Effects of Alcohol Consumption and Heavy Drinking on the Adolescent Brain: A Scoping Review Protocol.

Introduction: Alcohol consumption, specifically heavy drinking during adolescence, has been shown to be accompanied by adverse structural brain changes in adolescent drinkers. This scoping review will aim to quantify and evaluate the quality of studies in which magnetic resonance imaging (MRI) techniques are used to assess regional brain deficits among adolescents who consume alcohol. Methods and analysis: This scoping review will be conducted following the Arksey and O'Malley scoping review methodology framework and will be reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews (PRISMA-ScR) guidelines. Literature will be searched for the period January 1999 to March 2021. Two reviewers will independently screen titles/abstracts and full-texts in two consecutive screening stages. Eligible studies will be independently reviewed to ensure that inclusion criteria are met. Cohen's Kappa (κ) will be used to calculate inter-rater agreement. A third reviewer will resolve any disagreements. The Joanna Briggs Institute (JBI) Appraisal Tools will be used for quality appraisal of the included studies. Findings will be reported by means of a narrative overview, tabular presentation of study characteristics, and quality assessment, and a thematic analysis of major themes. This scoping review has been registered with the Open Science Framework. Ethics and dissemination: Scoping reviews do not require ethical approval, however, this review forms part of a larger study that has obtained approval from the Faculty of Health and Medical Sciences, Health Research Ethics Committee at Stellenbosch University (S20/04/086). Findings will be disseminated by means of peer-reviewed publications and conferences.

Examining the effects of HIV self-testing compared to standard HIV testing services in the general population: A systematic review and meta-analysis.

BACKGROUND: We updated a 2017 systematic review and compared the effects of HIV self-testing (HIVST) to standard HIV testing services to understand effective service delivery models among the general population. METHODS: We included randomized controlled trials (RCTs) comparing testing outcomes with HIVST to standard testing in the general population and published between January 1, 2006 and June 4, 2019. Random effects meta-analysis was conducted and pooled risk ratios (RRs) were reported. The certainty of evidence was determined using the GRADE methodology. FINDINGS: We identified 14 eligible RCTs, 13 of which were conducted in sub-Saharan Africa. Support provided to self-testers ranged from no/basic support to one-on-one in-person support. HIVST increased testing uptake overall (RR:2.09; 95% confidence interval: 1.69-2.58; p < 0.0001;13 RCTs; moderate certainty evidence) and by service delivery model including facility-based distribution, HIVST use at facilities, secondary distribution to partners, and community-based distribution. The number of persons diagnosed HIV-positive among those tested (RR:0.81, 0.45-1.47; p = 0.50; 8 RCTs; moderate certainty evidence) and number linked to HIV care/treatment among those diagnosed (RR:0.95, 0.79-1.13; p = 0.52; 6 RCTs; moderate certainty evidence) were similar between HIVST and standard testing. Reported harms/adverse events with HIVST were rare and appeared similar to standard testing (RR:2.52: 0.52-12.13; p = 0.25; 4 RCTs; very low certainty evidence). INTERPRETATION: HIVST appears to be safe and effective among the general population in sub-Saharan Africa with a range of delivery models. It identified and linked additional people with HIV to care. These findings support the wider availability of HIVST to reach those who may not otherwise access testing.

Guidelines for Reporting Trial Protocols and Completed Trials Modified Due to the COVID-19 Pandemic and Other Extenuating Circumstances: The CONSERVE 2021 Statement.

Importance: Extenuating circumstances can trigger unplanned changes to randomized trials and introduce methodological, ethical, feasibility, and analytical challenges that can potentially compromise the validity of findings. Numerous randomized trials have required changes in response to the COVID-19 pandemic, but guidance for reporting such modifications is incomplete. Objective: As a joint extension for the CONSORT and SPIRIT reporting guidelines, CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances. Evidence: A panel of 37 international trial investigators, patient representatives, methodologists and statisticians, ethicists, funders, regulators, and journal editors convened to develop the guideline. The panel developed CONSERVE following an accelerated, iterative process between June 2020 and February 2021 involving (1) a rapid literature review of multiple databases (OVID Medline, OVID EMBASE, and EBSCO CINAHL) and gray literature sources from 2003 to March 2021; (2) consensus-based panelist meetings using a modified Delphi process and surveys; and (3) a global survey of trial stakeholders. Findings: The rapid review yielded 41 673 citations, of which 38 titles were relevant, including emerging guidance from regulatory and funding agencies for managing the effects of the COVID-19 pandemic on trials. However, no generalizable guidance for all circumstances in which trials and trial protocols might face unanticipated modifications were identified. The CONSERVE panel used these findings to develop a consensus reporting guidelines following 4 rounds of meetings and surveys. Responses were received from 198 professionals from 34 countries, of whom 90% (n = 178) indicated that they understood the concept definitions and 85.4% (n = 169) indicated that they understood and could use the implementation tool. Feedback from survey respondents was used to finalize the guideline and confirm that the guideline's core concepts were applicable and had utility for the trial community. CONSERVE incorporates an implementation tool and checklists tailored to trial reports and trial protocols for which extenuating circumstances have resulted in important modifications to the intended study procedures. The checklists include 4 sections capturing extenuating circumstances, important modifications, responsible parties, and interim data analyses. Conclusions and Relevance: CONSERVE offers an extension to CONSORT and SPIRIT that could improve the transparency, quality, and completeness of reporting important modifications to trials in extenuating circumstances such as COVID-19.

The association between silica exposure, silicosis and tuberculosis: a systematic review and meta-analysis.

BACKGROUND: While the association between occupational inhalation of silica dust and pulmonary tuberculosis has been known for over a century, there has never been a published systematic review, particularly of experience in the current era of less severe silicosis and treatable tuberculosis. We undertook a systematic review of the evidence for the association between (1) silicosis and pulmonary tuberculosis, and (2) silica exposure and pulmonary tuberculosis controlling for silicosis, and their respective exposure-response gradients. METHODS: We searched PUBMED and EMBASE, and selected studies according to a priori inclusion criteria. We extracted, summarised and pooled the results of published case-control and cohort studies of silica exposure and/or silicosis and incident active tuberculosis. Study quality was assessed on the Newcastle-Ottawa Scale. Where meta-analysis was possible, effect estimates were pooled using inverse-variance weighted random-effects models. Otherwise narrative and graphic synthesis was undertaken. Confidence regarding overall effect estimates was assessed using the GRADE schema. RESULTS: Nine studies met the inclusion criteria. Meta-analysis of eight studies of silicosis and tuberculosis yielded a pooled relative risk of 4.01 (95% confidence interval (CI) 2.88, 5.58). Exposure-response gradients were strong with a low silicosis severity threshold for increased risk. Our GRADE assessment was high confidence in a strong association. Meta-analysis of five studies of silica exposure controlling for or excluding silicosis yielded a pooled relative risk of 1.92 (95% CI 1.36, 2.73). Exposure-response gradients were observable in individual studies but not finely stratified enough to infer an exposure threshold. Our GRADE assessment was low confidence in the estimated effect owing to inconsistency and use of proxies for silica exposure. CONCLUSIONS: The evidence is robust for a strongly elevated risk of tuberculosis with radiological silicosis, with a low disease severity threshold. The effect estimate is more uncertain for silica exposure without radiological silicosis. Research is needed, particularly cohort studies measuring silica exposure in different settings, to characterise the effect more accurately as well as the silica exposure threshold that could be used to prevent excess tuberculosis risk.

Ready-to-Use Therapeutic Food (RUTF) Containing Low or No Dairy Compared to Standard RUTF for Children with Severe Acute Malnutrition: A Systematic Review and Meta-Analysis.

Ready-to-use therapeutic food (RUTF) containing less dairy may be a lower-cost treatment option for severe acute malnutrition (SAM). The objective was to understand the effectiveness of RUTF containing alternative sources of protein (nondairy), or <50% of protein from dairy products, compared with standard RUTF in children with SAM. The Cochrane Library, MEDLINE, Embase, CINAHL, and Web of Science were searched using terms relating to RUTF. Studies were eligible if they included children with SAM and evaluated RUTF with <50% of protein from dairy products compared with standard RUTF. Meta-analysis and meta-regression were completed to assess the effectiveness of intervention RUTF on a range of child outcomes. The quality of the evidence across outcomes was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A total of 5868 studies were identified, of which 8 articles of 6 studies met the inclusion criteria evaluating 7 different intervention RUTF recipes. Nondairy or lower-dairy RUTF showed less weight gain (standardized mean difference: -0.20; 95% CI: -0.26, -0.15; P < 0.001), lower recovery (relative risk ratio: 0.93; 95% CI: 0.87, 1.00; P = 0.046), and lower weight-for-age z scores (WAZ) near program discharge (mean difference: -0.10; 95% CI: -0.20, 0.0; P = 0.047). Mortality, time to recovery, default (consecutive absences from outpatient therapeutic feeding program visits), nonresponse, and other anthropometric measures did not differ between groups. The certainty of evidence was high for weight gain and ranged from very low to moderate for other outcomes. RUTF with lower protein from dairy or dairy-free RUTF may not be as effective as standard RUTF for treatment of children with SAM based on weight gain, recovery, and WAZ evaluated using meta-analysis, although further research is required to explore the potential of alternative formulations. This review was registered at https://www.crd.york.ac.uk/prospero/ as CRD42020160762.

Concept and development of an interactive tool for trial recruitment planning and management.

BACKGROUND: Predicting and monitoring recruitment in large, complex trials is essential to ensure appropriate resource management and budgeting. In a novel partnership between clinical trial investigators of the South African Medical Research Council and industrial engineers from the Stellenbosch University Health Systems Engineering and Innovation Hub, we developed a trial recruitment tool (TRT). The objective of the tool is to serve as a computerised decisions-support system to aid the planning and management phases of the trial recruitment process. METHOD: The specific requirements of the TRT were determined in several workshops between the partners. A Poisson process simulation model was formulated and incorporated in the TRT to predict the recruitment duration. The assumptions underlying the model were made in consultation with the trial team at the start of the project and were deemed reasonable. Real-world data extracted from a current cluster trial, Project MIND, based in 24 sites in South Africa was used to verify the simulation model and to develop the monitoring component of the TRT. RESULTS: The TRT comprises a planning and monitoring component. The planning component generates different trial scenarios for predicted trial recruitment duration based on user inputs, e.g. number of sites, initiation delays. The monitoring component uses and analyses the data retrieved from the trial management information system to generate different levels of information, displayed visually on an interactive, user-friendly dashboard. Users can analyse the results at trial or site level, changing input parameters to see the resultant effect on the duration of trial recruitment. CONCLUSION: This TRT is an easy-to-use tool that assists in the management of the trial recruitment process. The TRT has potential to expedite improved management of clinical trials by providing the appropriate information needed for the planning and monitoring of the trial recruitment phase. This TRT extends prior tools describing historic recruitment only to using historic data to predict future recruitment. The broader project demonstrates the value of collaboration between clinicians and engineers to optimise their respective skillsets.

Comparing the effects of HIV self-testing to standard HIV testing for key populations: a systematic review and meta-analysis.

BACKGROUND: We update a previous systematic review to inform new World Health Organization HIV self-testing (HIVST) recommendations. We compared the effects of HIVST to standard HIV testing services to understand which service delivery models are effective for key populations. METHODS: We did a systematic review of randomised controlled trials (RCTs) which compared HIVST to standard HIV testing in key populations, published from 1 January 2006 to 4 June 2019 in PubMed, Embase, Global Index Medicus, Social Policy and Practice, PsycINFO, Health Management Information Consortium, EBSCO CINAHL Plus, Cochrane Library and Web of Science. We extracted study characteristic and outcome data and conducted risk of bias assessments using the Cochrane ROB tool version 1. Random effects meta-analyses were conducted, and pooled effect estimates were assessed along with other evidence characteristics to determine the overall strength of the evidence using GRADE methodology. RESULTS: After screening 5909 titles and abstracts, we identified 10 RCTs which reported on testing outcomes. These included 9679 participants, of whom 5486 were men who have sex with men (MSM), 72 were trans people and 4121 were female sex workers. Service delivery models included facility-based, online/mail and peer distribution. Support components were highly diverse and ranged from helplines to training and supervision. HIVST increased testing uptake by 1.45 times (RR=1.45 95% CI 1.20, 1.75). For MSM and small numbers of trans people, HIVST increased the mean number of HIV tests by 2.56 over follow-up (mean difference = 2.56; 95% CI 1.24, 3.88). There was no difference between HIVST and SoC in regard to positivity among tested overall (RR = 0.91; 95% CI 0.73, 1.15); in sensitivity analysis of positivity among randomised HIVST identified significantly more HIV infections among MSM and trans people (RR = 2.21; 95% CI 1.20, 4.08) and in online/mail distribution systems (RR = 2.21; 95% CI 1.14, 4.32). Yield of positive results in FSW was not significantly different between HIVST and SoC. HIVST reduced linkage to care by 17% compared to SoC overall (RR = 0.83; 95% CI 0.74, 0.92). Impacts on STI testing were mixed; two RCTs showed no decreases in STI testing while one showed significantly lower STI testing in the intervention arm. There were no negative impacts on condom use (RR = 0.95; 95% CI 0.83, 1.08), and social harm was very rare. CONCLUSIONS: HIVST is safe and increases testing uptake and frequency as well as yield of positive results for MSM and trans people without negative effects on linkage to HIV care, STI testing, condom use or social harm. Testing uptake was increased for FSW, yield of positive results were not and linkage to HIV care was worse. Strategies to improve linkage to care outcomes for both groups are crucial for effective roll-out.

Self-care interventions for sexual and reproductive health and rights for advancing universal health coverage.

WHO's normative guidance on self-care interventions for sexual and reproductive health and rights (SRHR) promotes comprehensive, integrated and people-centred approaches to health service delivery. Implementation of self-care interventions within the context of human rights, gender equality, and a life course approach, offers an underused opportunity to improve universal health coverage (UHC) for all. Results from an online global values and preferences survey provided lay persons' and healthcare providers' perspectives on access, acceptability, and implementation considerations. This analysis examines 326 qualitative responses to open-ended questions from healthcare providers (n = 242) and lay persons (n = 70) from 77 countries. Participants were mostly women (66.9%) and were from the Africa (34.5%), America (32.5%), South-East Asia (5.6%), European (19.8%), Eastern Mediterranean (4.8%), and Western Pacific regions (2.8%). Participants perceived multiple benefits of self-care interventions for SRHR, including: reduced exposure to stigma, discrimination and access barriers, increased confidentiality, empowerment, self-confidence, and informed decision-making. Concerns include insufficient knowledge, affordability, and possible side-effects. Implementation considerations highlighted the innovative approaches to linkages with health services. Introduction of self-care interventions is a paradigm shift in health care delivery bridging people and communities through primary health care to reach UHC. Self-care interventions can be leveraged by countries as gateways for reaching more people with quality, accessible and equitable services that is critical for achieving UHC. The survey results underscored the urgent need to reduce stigma and discrimination, increase access to and improve knowledge of self-care interventions for SRHR for laypersons and healthcare providers to advance SRHR.

Prioritising gender, equity, and human rights in a GRADE-based framework to inform future research on self care for sexual and reproductive health and rights.

Introduction: In January 2019, the WHO reviewed evidence to develop global recommendations on self-care interventions for sexual and reproductive health and rights (SRHR). Identification of research gaps is part of the WHO guidelines development process, but reliable methods to do so are currently lacking with gender, equity and human rights (GER) infrequently prioritised. Methods: We expanded a prior framework based on Grading of Evidence, Assessment, Development and Evaluation (GRADE) to include GER. The revised framework is applied systematically during the formulation of research questions and comprises: (1) assessment of the GRADE strength and quality rating of recommendations; (2) mandatory inclusion of research questions identified from a global stakeholder survey; and (3) selection of the GER standards and principles most relevant to the question through discussion and consensus. For each question, we articulated: (1) the most appropriate and robust study design; (2) an alternative pragmatic design if the ideal design was not feasible; and (3) the methodological challenges facing researchers through identifying potential biases. Results: We identified 39 research questions, 7 overarching research approaches and 13 discrete feasible study designs. Availability and accessibility were most frequently identified as the GER standards and principles to consider when planning studies, followed by privacy and confidentiality. Selection and detection bias were the primary methodological challenges across mixed methods, quantitative and qualitative studies. A lack of generalisability potentially limits the use of study results with non-participation in research potentially highest in more vulnerable populations. Conclusion: A framework based on GRADE that includes stakeholders' values and identification of core GER standards and principles provides a practical, systematic approach to identifying research questions from a WHO guideline. Clear guidance for future studies will contribute to an anticipated 'living guidelines' approach within WHO. Foregrounding GER as a separate component of the framework is innovative but further elaboration to operationalise appropriate indicators for SRHR self-care interventions is required.

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.