Clinical prediction models in children that use repeated measurements with time-varying covariates: a scoping review.

BACKGROUND: Emerging evidence suggests that clinical prediction models that use repeated (time-varying) measurements within each patient may have higher predictive accuracy than models that use patient information from a single measurement. OBJECTIVE: To determine the breadth of the published literature reporting the development of clinical prediction models in children that use time-varying predictors. DATA SOURCES: MEDLINE, EMBASE and Cochrane databases. ELIGIBILITY CRITERIA: We included studies reporting the development of a multivariable clinical prediction model in children, with or without validation, to predict a repeatedly measured binary or time-to-event outcome and utilizing at least one repeatedly measured predictor. SYNTHESIS METHODS: We categorized included studies by the method used to model time-varying predictors. RESULTS: Of 99 clinical prediction model studies that had a repeated measurements data structure, only 27 (27%) used methods that incorporated the repeated measurements as time-varying predictors in a single model. Among these 27 time-varying prediction model studies, we grouped model types into nine categories: time-dependent Cox regression, generalized estimating equations, random effects model, landmark model, joint model, neural network, K-nearest neighbor, support vector machine and tree-based algorithms. Where there was comparison of time-varying models to single measurement models, using time-varying predictors improved predictive accuracy. CONCLUSIONS: Various methods have been used to develop time-varying prediction models in children, but there is a paucity of pediatric time-varying models in the literature. Incorporating time-varying covariates in pediatric prediction models may improve predictive accuracy. Future research in pediatric prediction model development should further investigate whether incorporation of time-varying covariates improves predictive accuracy. WHAT THIS SCOPING REVIEW ADDS: Of 99 clinical prediction model studies that had a repeated measurements data structure, only 27% used analytical methods that incorporated time-varying covariates. Future research in pediatric prediction model development should further investigate whether incorporation of time-varying covariates improves predictive accuracy. HOW TO USE THIS SCOPING REVIEW: We summarized methods used to develop pediatric clinical prediction models that incorporate repeated measurements with time-varying covariates. Researchers may use the findings of this review to identify appropriate analytical methods for developing a time-varying prediction model in pediatric care.

Exploring a syndemic of poverty, cumulative violence, and HIV vulnerability among refugee youth: multi-method insights from a humanitarian setting in Uganda.

Synergistic associations between social inequities and HIV vulnerabilities - known as a syndemic - are understudied with youth in humanitarian settings. We explored refugee youths' HIV prevention needs in Bidi Bidi Refugee Settlement, Uganda. This multi-methods study involved 6 focus groups and 12 in-depth individual interviews (IDI) with refugee youth (n = 60) aged 16-24, and IDI with refugee elders (n = 8) and healthcare providers (n = 8). We then conducted cross-sectional surveys with refugee youth (16-24 years) (n = 115) to assess: poverty, recent sexual and gender-based violence (SGBV), and condom engagement motivation (CEM) (wanting to learn about condoms for HIV prevention). Multivariable logistic regression was used to estimate adjusted odds ratios for associations between poverty and SGBV with CEM. Qualitative narratives revealed poverty and trauma elevated substance use, and these converged to exacerbate SGBV. SGBV and transactional sex increased HIV vulnerabilities. Among survey participants, poverty and recent SGBV were associated with reduced odds of CEM. The interaction between poverty and recent SGBV was significant: the predicted probability of CEM among youth who experienced both poverty and SGBV was almost half than among youth who experienced poverty alone, SGBV alone, or neither. Findings signal the confluence of poverty, violence, and substance use elevate refugee youth HIV vulnerabilities.

Associations between human milk oligosaccharides and infant growth in a Bangladeshi mother-infant cohort.

BACKGROUND: We aimed to estimate associations between human milk oligosaccharides (HMOs) and infant growth (length-for-age (LAZ) and weight-for-length (WLZ) z-scores) at 12 months postnatal age. METHODS: In this secondary analysis of data from a maternal vitamin D trial in Dhaka, Bangladesh (N = 192), absolute concentrations of HMOs were measured in 13 ± 1 week(s) postpartum milk samples, infant anthropometric measurements were obtained soon after birth and at 12 months postpartum, and infant feeding was classified during 6 months postpartum. Associations between individual HMOs or HMO groups and LAZ or WLZ were estimated by multivariable linear regression adjusting for infant feeding pattern, maternal secretor status, and other potential confounders. RESULTS: The concentrations of 6'sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated HMOs were inversely associated with LAZ at 12 months of age, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months. These associations were robust in analyses restricted to infants who were primarily exclusively/predominantly fed human milk during the first 3 (or 6) months. CONCLUSIONS: Since HMOs are both positively and negatively associated with postnatal growth, there is a need for randomized trials to estimate the causal benefits and risks of exogenously administered HMOs on infant growth and other health outcomes. IMPACT: 6'sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated human milk oligosaccharides (HMOs) were inversely associated with length-for-age z-scores (LAZ) at 12 months, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months among Bangladeshi infants. Associations between individual and grouped HMOs with infant length growth at 12 months were as strong or stronger in analyses restricted to infants who were exclusively or predominantly fed human milk up to 3 (or 6) months. Randomized trials are needed to characterize the effects of specific HMOs on infant growth, particularly in countries where postnatal linear growth faltering is common.

Findings from the Tushirikiane mobile health (mHealth) HIV self-testing pragmatic trial with refugee adolescents and youth living in informal settlements in Kampala, Uganda.

INTRODUCTION: Urban refugee youth remain underserved by current HIV prevention strategies, including HIV self-testing (HIVST). Examining HIVST feasibility with refugees can inform tailored HIV testing strategies. We examined if HIVST and mobile health (mHealth) delivery approaches could increase HIV testing uptake and HIV status knowledge among refugee youth in Kampala, Uganda. METHODS: We conducted a three-arm pragmatic controlled trial across five informal settlements grouped into three sites in Kampala from 2020 to 2021 with peer-recruited refugee youth aged 16-24 years. The intervention was HIVST and HIVST + mHealth (HIVST with bidirectional SMS), compared with standard of care (SOC). Primary outcomes were self-reported HIV testing uptake and correct status knowledge verified by point-of-care testing. Some secondary outcomes included: depression, HIV-related stigma, and adolescent sexual and reproductive health (SRH) stigma at three time points (baseline [T0], 8 months [T1] and 12 months [T2]). We used generalized estimating equation regression models to estimate crude and adjusted odds ratios comparing arms over time, adjusting for age, gender and baseline imbalances. We assessed study pragmatism across PRECIS-2 dimensions. RESULTS: We enrolled 450 participants (50.7% cisgender men, 48.7% cisgender women, 0.7% transgender women; mean age: 20.0, standard deviation: 2.4) across three sites. Self-reported HIV testing uptake increased significantly from T0 to T1 in intervention arms: HIVST arm: (27.6% [n = 43] at T0 vs. 91.2% [n = 135] at T1; HIVST + mHealth: 30.9% [n = 47] at T0 vs. 94.2% [n = 113] at T1]) compared with SOC (35.5% [n = 50] at T0 vs. 24.8% [ = 27] at T1) and remained significantly higher than SOC at T2 (p<0.001). HIV status knowledge in intervention arms (HIVST arm: 100% [n = 121], HIVST + mHealth arm: 97.9% [n = 95]) was significantly higher than SOC (61.5% [n = 59]) at T2. There were modest changes in secondary outcomes in intervention arms, including decreased depression alongside increased HIV-related stigma and adolescent SRH stigma. The trial employed both pragmatic (eligibility criteria, setting, organization, outcome, analysis) and explanatory approaches (recruitment path, flexibility of delivery flexibility, adherence flexibility, follow-up). CONCLUSIONS: Offering HIVST is a promising approach to increase HIV testing uptake among urban refugee youth in Kampala. We share lessons learned to inform future youth-focused HIVST trials in urban humanitarian settings.

A Participatory Comic Book Workshop to Improve Youth-Friendly Post-Rape Care in a Humanitarian Context in Uganda: A Case Study.

BACKGROUND: Graphic medicine formats, such as comic books in which health information is presented alongside images, may be a useful learning tool to improve post-rape care and youth-friendly service provision among health care providers in humanitarian contexts. We describe the development and pilot-testing of a workshop using a comic book to improve youth-friendly post-rape care with providers in Bidi Bidi refugee settlement, Uganda. PROGRAM DEVELOPMENT AND PILOTING: We conducted 6 focus groups with refugee young men (n=3) and women (n=3) aged 16-24 years and 28 in-depth individual interviews (refugee youth: n=12; health care providers: n=8; elders: n=8). Findings informed the development of a workshop that included a participatory comic book on sexual and gender-based violence (SGBV) and youth, SGBV stigma, youth-friendly health care, and post-exposure prophylaxis. Comic book illustrations specifically addressed health care confidentiality and examples of being a supportive health care provider. Then, we conducted a 1-day workshop with health care providers (n=20) that included structured activities addressing SGBV impacts and related stigma and included comic book discussions. Open-ended survey data were collected 8 weeks after the workshop to explore health care providers' experiences with the workshop, perceived impact of the intervention on their work, and support required to implement youth-friendly services for SGBV survivors. Qualitative data were analyzed using thematic approaches. Open-ended response data indicated that: comic book methods were informative and interactive; health care providers felt more empowered to offer youth-friendly services and spaces; and health care providers want additional SGBV training and institutional support for youth-friendly spaces and community engagement. IMPLICATIONS: A comic book intervention has the potential to meaningfully engage health care providers in humanitarian contexts to provide youth-friendly health care, acquire skills for engaging in SGBV prevention, create youth-friendly clinic spaces, and identify health care and community SGBV prevention needs.

Global inequity creates local insufficiency: A qualitative study of COVID-19 vaccine implementation challenges in low-and-middle-income countries.

INTRODUCTION: The COVID-19 pandemic has amplified pre-existing challenges to health promotion and care across the world, and particularly in low- and middle-income countries (LMICs). This qualitative study draws on data from a panel of immunisation experts and uses a novel framework of vaccine delivery domains to explore perspectives from those who live and work in these settings on the challenges to implementing COVID-19 vaccine programs in LMICs. METHODS: We conducted a thematic content analysis of 96 participant free text replies to questions from Round I of a three-round Delphi consensus study amongst global experts on COVID-19 vaccine implementation. RESULTS: Participant responses highlighted challenges to vaccine program implementation including issues related to equity; governance, decision-making, and financing; regulatory structures, planning, and coordination; prioritisation, demand generation, and communication; vaccine, cold chain, logistics, and infrastructure; service delivery, human resources, and supplies; and surveillance, monitoring, and evaluation. CONCLUSION: We reflect on our findings in light of global efforts to address vaccine inequity and emphasise three key areas salient to improving vaccination efforts during novel infectious disease outbreaks: 1) Ensuring safe and sustainable service delivery in communities and at points of care; 2) Strengthening systems for end-to-end delivery of vaccines, therapeutics, diagnostics, and essential supplies; 3) Transforming structural paradigms towards vaccine equity.

Mixed-methods findings from the Ngutulu Kagwero (agents of change) participatory comic pilot study on post-rape clinical care and sexual violence prevention with refugee youth in a humanitarian setting in Uganda.

There is a dearth of evidence-based post-rape clinical care interventions tailored for refugee adolescents and youth in low-income humanitarian settings. Comics, a low-cost, low-literacy and youth-friendly method, integrate visual images with text to spark emotion and share health-promoting information. We evaluated a participatory comic intervention to increase post-exposure prophylaxis (PEP) knowledge and acceptance, and prevent sexual and gender-based violence, in Bidi Bidi refugee settlement, Uganda. Following a formative qualitative phase, we conducted a pre-test post-test pilot study with refugee youth (aged 16-24 years) (n = 120). Surveys were conducted before (t0), after (t1), and two-months following (t2) workshops. Among participants (mean age: 19.7 years, standard deviation: 2.4; n = 60 men, n = 60 women), we found significant increases from t0 to t1, and from t0 to t2 in: (a) PEP knowledge and acceptance, (b) bystander efficacy, and (c) resilient coping. We also found significant decreases from t0 to t1, and from t0 to t2 in sexual violence stigma and depression. Qualitative feedback revealed knowledge and skills acquisition to engage with post-rape care and violence prevention, and increased empathy to support survivors. Survivor-informed participatory comic books are a promising approach to advance HIV prevention through increased PEP acceptance and reduced sexual violence stigma with refugee youth.Trial registration: ClinicalTrials.gov identifier: NCT04656522.

Associations between water insecurity and depression among refugee adolescents and youth in a humanitarian context in Uganda: cross-sectional survey findings.

BACKGROUND: Water insecurity is linked to poor mental health through intrapersonal, relational and community-based stressors. We examined water insecurity and depression among refugee youth in Bidi Bidi, Uganda. METHODS: We conducted a cross-sectional survey and multivariable ordinal logistic regression to examine associations between water insecurity and depression severity, adjusting for gender, resilience, social support and food insecurity. RESULTS: Among participants (n=115; mean age: 19.7 y, SD 2.3), 80.0% reported water insecurity and 18.3% had moderate/severe depression symptoms. Water insecurity was independently associated with higher levels of depression severity (adjusted OR: 5.61; 95% CI 1.20 to 26.30; p=0.03). CONCLUSIONS: Findings suggest water insecurity was commonplace and associated with depression. Water insecurity could be integrated in refugee mental health promotion by policymakers and community-based programmers.

Todurujo na Kadurok (empowering youth): study protocol of an HIV self-testing and edutainment comic cluster randomised trial among refugee youth in a humanitarian setting in Uganda.

INTRODUCTION: Refugees experience HIV vulnerabilities due to the confluence of displacement, violence and poverty. HIV self-testing, understudied with refugees, is a promising method to increase testing uptake, yet challenges remain with linkages to confirmatory testing following a positive HIV self-test. This study aims to evaluate the effectiveness of HIV self-testing kits and 'edutainment' comics in increasing HIV testing and HIV status knowledge among refugee youth aged 16-24 years in Bidi Bidi Refugee Settlement, Uganda. METHODS AND ANALYSIS: This study will be conducted in Bidi Bidi. We conducted a qualitative formative phase with focus groups (n=40) to generate knowledge of barriers and facilitators of HIV prevention, testing and care among refugee youth (aged 16-24) in Bidi Bidi. These findings were used to create comic scenarios aligning with edutainment approaches to health promotion and inform a four-arm cluster randomised controlled trial in Bidi Bidi using a 2×2 factorial design: (1) HIV self-testing alongside edutainment comics, (2) HIV self-testing alone, (3) edutainment comic alone and (4) standard of care. The target sample size will be 120 youth (30 per arm), who will be enrolled in the trial and followed for 3 months. Data will be collected at baseline and 3 months after enrolment. The primary outcomes (HIV testing frequency, HIV status knowledge) and secondary outcomes (linkage to confirmatory HIV testing, HIV care linkage, HIV self-test kit use, HIV-related stigma, HIV knowledge, safer sex efficacy, condom use, adolescent sexual and reproductive health (SRH) stigma, sexual relationship power, access to SRH services) will be evaluated using descriptive statistics and regression analyses. ETHICS AND DISSEMINATION: This study was approved by the University of Toronto Research Ethics Board, Mildmay Uganda Research Ethics Committee and the Uganda National Council for Science and Technology. Results will be shared in peer-reviewed publications and community knowledge sharing. TRIAL REGISTRATION NUMBER: NCT05213689.

Social contextual factors associated with lifetime HIV testing among the Tushirikiane urban refugee youth cohort in Kampala, Uganda: Cross-sectional findings.

BACKGROUND: Urban refugee youth may live in social contexts characterized by structural drivers of HIV such as poverty and violence. Knowledge gaps remain regarding HIV testing practices among urban refugee youth, despite the increasing trend toward refugee settlement in urban contexts. This study examined social contextual factors associated with lifetime HIV testing among urban refugee youth in Kampala, Uganda. METHODS: We conducted a community-based study with a peer-recruited cohort of urban refugee youth aged 16-24 years living in Kampala's informal settlements, and present baseline cross-sectional findings. We conducted descriptive statistics and logistic regression to examine socio-demographic (e.g., gender and age), material (e.g., income insecurity and education), relational (e.g., social support), and symbolic contexts (e.g., HIV-related stigma and intimate partner violence (IPV]) associated with lifetime HIV testing. RESULTS: Participants (n = 450) had a mean age of 20.4 years (standard deviation: 2.4 years), most lived in Uganda for 1-5 years (53.2%), and less than half reported lifetime HIV testing (43.4%). In multivariable analyses, odds of lifetime HIV testing were higher among youth with secondary school education or higher (adjusted odds ratio (aOR]: 2.30, 95% confidence interval (CI]: 1.27-4.17), currently employed (aOR: 1.79, 95% CI: 1.03-3.10), and reporting IPV (aOR: 3.61, 95% CI: 1.43-9.10). Having children was marginally associated with HIV testing (aOR: 2.17, 95% CI: 0.98-4.81, p = 0.052). CONCLUSIONS: Findings demonstrate suboptimal HIV testing and the importance of tailored strategies to reach urban refugee youth who are unemployed and have limited formal education. There is a need to meaningfully engage urban refugee youth to create enabling environments for sexual health.

Sexual and reproductive health factors associated with child, early and forced marriage and partnerships among refugee youth in a humanitarian setting in Uganda: Mixed methods findings.

Preventing early and forced marriage is a global priority, however, sexual and reproductive health (SRH) among youth remains understudied in humanitarian settings. This study examined child, early and forced marriage and partnership (CEFMP) among young refugees in Bidi Bidi refugee settlement, Uganda, and associations with SRH outcomes among young women. This mixed-methods study involved a qualitative phase with young (16-24 years) sexual violence survivors (n=58), elders (n=8) and healthcare providers (n=10), followed by a quantitative phase among refugee youth (16-24 years; n=120) during which sociodemographic and SRH data were collected. We examined SRH outcome differences by CEFMP using Fisher's exact test. Qualitative data showed that CEFMP was a significant problem facing refugee young women driven by stigma, gender norms and poverty. Among youth refugee survey participants, nearly one-third (31.7%) experienced CEFMP (57.9% women, 42.1% men). Among women in CEFMP compared to those who were not, a significantly higher proportion reported forced pregnancy (50.0% vs. 18.4%, p-value=0.018), forced abortion (45.4% vs. 7.0%, p-value=0.002), and missed school due to sexual violence (94.7% vs. 63.0%, p-value=0.016). This study illustrates the need for innovative community-engaged interventions to end CEFMP in humanitarian contexts in order to achieve sexual and reproductive health and rights for youth.

Identifying priority challenges and solutions for COVID-19 vaccine delivery in low- and middle-income countries: A modified Delphi study.

BACKGROUND: The rapid implementation of global COVID-19 vaccination programs has surfaced many challenges and inequities, particularly in low- and middle-income countries (LMICs). However, there continues to be a lack of consensus on which challenges are global priorities for action, and how to best respond to them. This study uses consensus-based methods to identify and rank the most important challenges and solutions for implementation of COVID-19 vaccination programs in LMICs. METHODS: We conducted a three-round modified Delphi study with a global panel of vaccine delivery experts. In Round I, panelists identified broad topical challenges and solutions. Responses were collated and coded into distinct items. Through two further rounds of structured, iterative surveys panelists reviewed and ranked the identified items. Responses were analyzed qualitatively and quantitatively to achieve consensus on the most important COVID-19 vaccine delivery challenges and solutions. RESULTS: Of the 426 invited panelists, 96 completed Round I, 56 completed Round II, and 39 completed Round III. Across all three rounds there was equal representation by gender, and panelists reported work experience in all World Bank regions and across a variety of content areas and organizations. Of the 64 initially identified items, the panel achieved consensus on three challenges and 10 solutions. Challenges fell under themes of structural factors and infrastructure and human and material resources, while solutions also included items within themes of communication, community engagement, and access and planning, processes, and operations. CONCLUSION: COVID-19 vaccine delivery is challenged by long-standing and structural inequities that disadvantage health service delivery in LMICs. These findings can, and should, be used by global health organizations to efficiently and optimally direct resources to respond to these key challenges and solutions.

The prevalence and correlates of depression before and after the COVID-19 pandemic declaration among urban refugee adolescents and youth in informal settlements in Kampala, Uganda: A longitudinal cohort study.

PURPOSE: There is scant research examining urban refugee youth mental health outcomes, including potential impacts of the COVID-19 pandemic. We examine prevalence and ecosocial risk factors of depression in the periods before and after the COVID-19 pandemic declaration among urban refugee youth in Kampala, Uganda. METHODS: Data from a cohort of refugee youth (n = 367) aged 16-24 years were collected in periods before (February 2020) and after (December 2020) the WHO COVID-19 pandemic declaration. We developed crude and adjusted generalized estimating equation logistic regression models to examine demographic and ecosocial factors (food insecurity, social support, intimate partner violence) associated with depression, and include time-ecosocial interactions to examine if associations differed before and after the pandemic declaration. RESULTS: The prevalence of depression was high, but there was no significant difference before (27.5%), and after (28.9%) the pandemic declaration (P = .583). In adjusted models, food insecurity (aOR: 2.54; 95% CI: 1.21-5.33) and experiencing violence (aOR: 2.53; 95% CI: 1.07-5.96) were associated with increased depression, and social support was associated with decreased depression (aOR: 0.85; 95% CI: 0.81-0.89). CONCLUSIONS: These findings highlight the urgent need for interventions to address chronic depression, food insecurity, and ongoing effects of violence exposure among urban refugee youth in Kampala.

Ngutulu Kagwero (agents of change): study design of a participatory comic pilot study on sexual violence prevention and post-rape clinical care with refugee youth in a humanitarian setting in Uganda.

With over 1.4 million refugees, Uganda is Sub-Saharan Africa's largest refugee-hosting nation. Bidi Bidi, Uganda's largest refugee settlement, hosts over 230,000 residents. There is a dearth of evidence-based sexual violence prevention and post-rape clinical care interventions in low- and middle-income humanitarian contexts tailored for refugee youth. Graphic medicine refers to juxtaposing images and narratives, often through using comics, to convey health promotion messaging. Comics can offer youth-friendly, low-cost, scalable approaches for sexual violence prevention and care. Yet there is limited empirical evaluation of comic interventions for sexual violence prevention and post-rape clinical care. This paper details the study design used to develop and pilot test a participatory comic intervention focused on sexual violence prevention through increasing bystander practices, reducing sexual violence stigma, and increasing post exposure prophylaxis (PEP) knowledge with youth aged 16-24 and healthcare providers in Bidi Bidi. Participants took part in a single-session peer-facilitated workshop that explored social, sexual, and psychological dimensions of sexual violence, bystander interventions, and post-rape clinical care. In the workshop, participants completed a participatory comic book based on narratives from qualitative data conducted with refugee youth sexual violence survivors. This pilot study employed a one-group pre-test/post-test design to assess feasibility outcomes and preliminary evidence of the intervention's efficacy. Challenges included community lockdowns due to COVID-19 which resulted in study implementation delays, political instability, and attrition of participants during follow-up surveys. Lessons learned included the important role of youth facilitation in youth-centred interventions and the promise of participatory comics for youth and healthcare provider engagement for developing solutions and reducing stigma regarding SGBV. The Ngutulu Kagwero (Agents of change) project produced a contextually and age-tailored comic intervention that can be implemented in future fully powered randomized controlled trials to determine effectiveness in advancing sexual violence prevention and care with youth in humanitarian contexts.

Mobile Health-Supported HIV Self-Testing Strategy Among Urban Refugee and Displaced Youth in Kampala, Uganda: Protocol for a Cluster Randomized Trial (Tushirikiane, Supporting Each Other).

BACKGROUND: HIV is the leading cause of mortality among youth in sub-Saharan Africa. Uganda hosts over 1.43 million refugees, and more than 83,000 live in Kampala, largely in informal settlements. There is limited information about HIV testing uptake and preferences among urban refugee and displaced youth. HIV self-testing is a promising method for increasing testing uptake. Further, mobile health (mHealth) interventions have been effective in increasing HIV testing uptake and could be particularly useful among youth. OBJECTIVE: This study aims to evaluate the feasibility and effectiveness of two HIV self-testing implementation strategies (HIV self-testing intervention alone and HIV self-testing combined with an mHealth intervention) in comparison with the HIV testing standard of care in terms of HIV testing outcomes among refugee/displaced youth aged 16 to 24 years in Kampala, Uganda. METHODS: A three-arm cluster randomized controlled trial will be implemented across five informal settlements grouped into three sites, based on proximity, and randomization will be performed with a 1:1:1 method. Approximately 450 adolescents (150 per cluster) will be enrolled and followed for 12 months. Data will be collected at the following three time points: baseline enrollment, 8 months after enrollment, and 12 months after enrollment. Primary outcomes (HIV testing frequency, HIV status knowledge, linkage to confirmatory testing, and linkage to HIV care) and secondary outcomes (depression, condom use efficacy, consistent condom use, sexual relationship power, HIV stigma, and adolescent sexual and reproductive health stigma) will be evaluated. RESULTS: The study has been conducted in accordance with CONSORT (Consolidated Standards of Reporting Trials) guidelines. The study has received ethical approval from the University of Toronto (June 14, 2019), Mildmay Uganda (November 11, 2019), and the Uganda National Council for Science and Technology (August 3, 2020). The Tushirikiane trial launched in February 2020, recruiting a total of 452 participants. Data collection was paused for 8 months due to COVID-19. Data collection for wave 2 resumed in November 2020, and as of December 10, 2020, a total of 295 participants have been followed-up. The third, and final, wave of data collection will be conducted between February and March 2021. CONCLUSIONS: This study will contribute to the knowledge of differentiated HIV testing implementation strategies for urban refugee and displaced youth living in informal settlements. We will share the findings in peer-reviewed manuscripts and conference presentations. TRIAL REGISTRATION: ClinicalTrials.gov NCT04504097; https://clinicaltrials.gov/ct2/show/NCT04504097. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26192.

The Human-Milk Oligosaccharide Profile of Lactating Women in Dhaka, Bangladesh.

BACKGROUND: Human-milk oligosaccharides (HMOs) are an abundant component of human milk that have health-related effects on breastfeeding infants. Since variation in HMO composition can be explained by maternal and environmental factors, understanding the diversity in HMOs across settings and identifying context-specific factors associated with HMO abundances is important. OBJECTIVES: The aim was to describe the HMO profile of Bangladeshi women and to estimate the effect of maternal vitamin D supplementation on HMO composition. METHODS: In a cross-sectional analysis of data and samples from the Maternal Vitamin D for Infant Growth trial in Dhaka, Bangladesh (clinicaltrials.gov; NCT01924013), 192 participants were randomly selected including 96 from each of the placebo and highest-dose vitamin D supplementation groups. In mid-feed breast milk samples collected at a mean (±SD) postpartum age of 93 ± 7 d, absolute and relative abundances of 19 HMOs were analyzed by HPLC. "Secretors" were defined as participants with 2'fucosyllactose concentrations >350 nmol/mL. Associations between HMO concentrations and selected maternal or environmental factors were estimated by multivariable linear regression, adjusting for vitamin D group allocation and secretor status. HMO profiles of Bangladeshi women were compared with data from other international cohorts. RESULTS: Overall, 34% (65/192) of participants were nonsecretors. Secretor status was associated with the concentrations of total HMOs and 79% (15/19) of individual HMOs. Vitamin D supplementation did not affect the total or individual concentration of any measured HMO. 3-Fucosyllactose concentration was significantly higher in breast milk samples collected in December to February compared with samples collected in March to May. HMO composition was similar to other previously reported cohorts. CONCLUSIONS: The HMO profile of Bangladeshi women is predominantly determined by secretor status. Context-specific HMO data may improve understanding of the effects of HMOs on the infant microbiome and health and guide the development of HMO-containing interventions.

Using Experiential Simulation-Based Learning to Increase Engagement in Global Health Education: an Evaluation of Self-reported Participant Experience.

BACKGROUND: Simulations aim to supplement historic teacher-centric methods by facilitating experiential, self-guided learning and the application of students' knowledge in a controlled environment. The objective of our study is to describe the methodology of developing and facilitating simulations, and to assess their effectiveness as an educational tool for global health training. METHODS: We describe the methodology used by Global Health Sim between October 2016 and March 2019 to design and facilitate simulations for participants at the high school through graduate school levels, and at conferences and online. Using a mixed-methods evaluation design, we assessed self-reported quantitative measures of content knowledge before and after participating in the simulation and different aspects of the simulation experience. We also conducted a qualitative thematic analysis of the experience and lessons learned as reported by evaluation respondents. RESULTS: We conducted a total of 20 simulations on six unique topics for 213 evaluation respondents. Self-reported knowledge of the topic increased an average of 3.3 points on a 10-point scale (4.1-7.4) and the seven aspects of the experience were rated highly (3-5 points on a 5-point Likert scale). Thematic analysis revealed an increased understanding of the complexity of global health problems and strategies for effectively responding to issues in a multidisciplinary manner. CONCLUSIONS: Respondents valued the opportunity to learn about the complexities of responding to global health events, which confirmed that simulations can be utilized as teaching tools for students and professionals. Further research is required to assess the long-term educational impact of simulations in global health.

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations.

Arguments against routine administration of probiotics for NEC prevention.

PURPOSE OF REVIEW: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality among premature neonates. Although randomized trials have shown that probiotics may be efficacious in the prevention of NEC, their use has not been universally adopted in the neonatal intensive care unit (NICU). Caveats regarding routine probiotic supplementation for the prevention of NEC are summarized in this review. RECENT FINDINGS: Accumulating evidence indicates that prophylactic probiotic supplementation in preterm infants can reduce the incidence of NEC. However, substantial knowledge gaps, regulatory issues, and implementation challenges should be addressed before probiotics are introduced as standard of care for all preterm neonates. Limitations of published trial data have made it challenging to define regimens that optimize efficacy and safety in specific patient subgroups. Moreover, the current probiotic market lacks rigorous regulatory oversight, which could raise concerns about the quality and safety of probiotic products. Finally, implementation pitfalls include risks of cross-colonization and resource requirements to monitor and mitigate potential adverse events. SUMMARY: Probiotics have shown promise in the prevention of NEC. However, there is insufficient evidence to guide the selection of optimal regimens. Furthermore, issues related to regulatory and institutional oversight should be addressed before supplementation is routinely implemented in NICUs.

Acquired Resistance to Antituberculosis Drugs in England, Wales, and Northern Ireland, 2000-2015.

Among tuberculosis (TB) patients, acquired resistance to anti-TB drugs represents a failure in the treatment pathway. To improve diagnosis and care for patients with drug-resistant TB, we examined the epidemiology and risk factors associated with acquired drug resistance during 2000-2015 among TB patients in England, Wales, and Northern Ireland. We found acquired resistance in 0.2% (158/67,710) of patients with culture-confirmed TB. Using multivariate logistic regression, we identified the following factors associated with acquired drug resistance: having pulmonary disease; initial resistance to isoniazid, rifampin, or both; a previous TB episode; and being born in China or South Africa. Treatment outcomes were worse for patients with than without acquired resistance. Although acquired resistance is rare in the study area, certain patient groups are at higher risk. Identifying these patients and ensuring that adequate resources are available for treatment may prevent acquisition of resistance, thereby limiting transmission of drug-resistant strains of mycobacteria.