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Abstract Background People with disabilities frequently experience barriers in seeking healthcare that lead to poorer health outcomes compared to people without disabilities. To overcome this, it is important to assess the accessibility of primary health facilities – broadly defined to include a disability-inclusive service provision – so as to document present status and identify areas for improvement. We aimed to identify, adapt and pilot test an appropriate tool to assess the accessibility of primary health facilities in Luuka District, Uganda. Methods We conducted a rapid literature review to identify appropriate tools, selecting the Disability Awareness Checklist (DAC) on account of its relative brevity and development as a sensitization and action tool. We undertook three rounds of adaptation, working together with youth researchers (aged 18–35) with disabilities who then underwent 2 days of training as DAC facilitators. The adapted tool comprised 71 indicators across four domains and 12 sub-domains. We also developed a structured feedback form for facilitators to complete with healthcare workers. We calculated median accessibility scores overall, per domain and per sub-domain, and categorised feedback form suggestions by type and presumed investment level. We pilot-tested the adapted tool in 5 primary health facilities in one sub-district of Luuka, nested within a pilot healthcare worker training on disability. Results The median overall facility accessibility score was 17.8% (range 12.3–28.8). Facility scores were highest in the universal design and accessibility domain (25.8%, 22.6–41.9), followed by reasonable accommodation (20.0%, 6.7–33.3). Median scores for capacity of facility staff (6.67%, 6.7–20.0), and linkages to other services were lower (0.0%, 0–25.0). Within the feedback forms, there were a median of 21 suggestions (range 14–26) per facility. Most commonly, these were categorised as minor structural changes (20% of suggestions), with a third categorised as no (2%) or low (33%) cost, and the majority (40%) medium cost. Conclusions Overall accessibility scores were low, with many opportunities for low-cost improvement at the facility level. We did not identify any issues with the implementation of the tool, suggesting few further adaptations are required for its future use in this setting.

With a long-term aim of empowering researchers everywhere to contribute to work on language development, we organized the First Truly Global /L+/ International Summer/Winter School on Language Acquisition, a free 5-day virtual school for early career researchers. In this paper, we describe the school, our experience organizing it, and lessons learned. The school had a diverse organizer team, composed of 26 researchers (17 from under represented areas: Subsaharan Africa, South and Southeast Asia, and Central and South America); and a diverse volunteer team, with a total of 95 volunteers from 35 different countries, nearly half from under represented areas. This helped world-wide Page 5 of 5 promotion of the school, leading to 958 registrations from 88 different countries, with 300 registrants (based in 63 countries, 80% from under represented areas) selected to participate in the synchronous aspects of the event. The school employed asynchronous (pre-recorded lectures, which were close-captioned) and synchronous elements (e.g., discussions to place the recorded lectures into participants' context; networking events) across three time zones. A post-school questionnaire revealed that 99% of participants enjoyed taking part in the school. Not with standing these positive quantitative outcomes, qualitative comments suggested we fell short in several areas, including the geographic diversity among lecturers and greater customization of contents to the participants' contexts. Although much remains to be done to promote inclusivity in linguistic research, we hope our school will contribute to empowering researchers to investigate and publish on language acquisition in their home languages, to eventually result in more representative theories and empirical generalizations.

Robert O Opoka,1 Sarah Kiguli,1 Andrew S Ssemata,2 Marjan Govaerts,3 Erik W Driessen3 1Department of Paediatrics and Child Health, 2Department of Psychiatry, College of Health Sciences, Makerere University, Kampala, Uganda; 3Faculty of Health, Medicine and Life Sciences, Maastricht University, the Netherlands Background: The objective structured clinical examination (OSCE) is a commonly used method of assessing clinical competence at various levels, including at the postgraduate level. How the OSCE impacts on learning in higher education is poorly described. In this study, we evaluated the perceptions of postgraduate trainees regarding the impact of the OSCE on their study and clinical behavior. Methods: We employed an explorative qualitative research design by conducting focus group discussions with 41 pediatric postgraduate trainees at the College of Health Science, Makerere University. A semi-structured tool was used to obtain the views and experiences of the trainees. Transcripts from the discussion were analyzed in an iterative manner using thematic content analysis. Results: The trainees reported the OSCEs as a fair and appropriate tool for assessing clinical competency at the postgraduate level. However, they noted that whereas OSCEs assess a broad range of skills and competencies relevant to their training, there were areas that they did not adequately assess. In particular, OSCEs did not adequately assess in-depth clinical knowledge or detailed history-taking skills. Overall, the majority of the trainees reported that the OSCEs inspired them to study widely and improve their procedural and communication skills. Conclusion: OSCEs are a useful tool for assessing clinical competencies in postgraduate education. However, the perceived limitations in their ability to assess complex skills raises concerns about their use as a standalone mode of assessment at the postgraduate level. Future studies should evaluate how use of OSCEs in combination with other assessment tools impacts on learning. Keywords: objective structured clinical examination, assessment, higher education, perceptions, clinical practice, study, learning behavior

Abstract Background There are 1.3 billion people with disabilities globally, and they frequently face barriers to accessing healthcare, contributing to their worse health and higher mortality. However, little research has explored patient-reported approaches to improve healthcare for persons with disabilities. Consequently, this study aimed to explore possible solutions and recommendations to address the existing barriers to access to healthcare for persons with disabilities in rural Uganda. Methods We conducted 27 semi-structured interviews with individuals with various disabilities in rural Luuka district, Eastern Uganda, between September and November 2022. The participants included individuals with visual impairment (n = 5), physical impairment (n = 5), hearing impairment (n = 6), multiple impairments (n = 5), intellectual/cognitive impairment (n = 5), and albinism (n = 1). Interviews were recorded, transcribed verbatim, and thematically analysed. We categorized the solutions using the Missing Billion disability-inclusive health systems framework. Results Our findings, framed within the health systems framework, revealed several critical themes. On the demand side, suggested solutions emphasized advocacy and sensitization for persons with disabilities, their communities, and caregivers about healthcare needs. Socio-economic empowerment and community-based health services were also highlighted as essential. On the supply side, participants stressed the importance of training healthcare workers on disability, facilitating dialogue and experience-sharing sessions, and employing health workers with disabilities. Additional recommendations included improving accessibility and reasonable accommodation, organizing inclusive services like special clinic days and outreaches, ensuring representation in health facility management, and establishing comprehensive rehabilitation services with affordable assistive devices. Conclusion The multifaceted solutions proposed by persons with disabilities highlight the complex challenges they face in accessing healthcare services and highlight the necessity for comprehensive, sustainable interventions. The call to action for policymakers and healthcare providers is to prioritise the incorporation of disability-inclusive practices and explore multi-dimensional approaches that foster a more inclusive healthcare environment that adequately meets the needs of persons with disabilities.

Objective The aim of the research was to explore the barriers to healthcare access for persons with various disabilities in rural Luuka district of Uganda. The findings will assist in appreciating the challenges persons with disabilities face in accessing Healthcare in a rural setting. These insights will contribute to the development of an intervention to improve healthcare access that is affordable, timely and acceptable.Design and participants This qualitative study formed the exploratory formative phase of the ‘Missing Billion’ project. A total of 27 participants with disabilities—visual impairment (n=5), physical impairment (n=5), multiple impairments (n=6) and intellectual/ cognitive impairment (n=5) were purposively selected to participate in in-depth interviews conducted by two experienced researchers. Participants were identified through contact lists provided by the district disability focal person and local disability associations, with additional participants identified through snowball sampling. Interviews with persons with hearing impairment (n=6) were conducted by a researcher with hearing impairment. The interviews were audio/video recorded and transcribed to facilitate thematic data analysis. We used the disability-inclusive health ‘Missing Billion’ framework to map and inform the barriers.Setting The study was conducted between September and November 2022 in rural communities in Luuka district, Eastern Uganda.Findings On the demand side, challenges revolved around autonomy and awareness, limited access to health information, lack of financial capacity and dependence on caregivers for healthcare choices left persons with disabilities feeling disempowered. On the supply side, discrimination and negative attitudes from healthcare workers were reported as prevalent. Absence of healthcare workers and service delivery delays impacted on healthcare access, resulting in poor care. Inaccessible healthcare facilities compounded issues, as they had limited accessibility features.Conclusions Complex and interconnected barriers underscore the pressing need for systemic changes to ensure equitable healthcare access for persons with disabilities in rural Uganda.

IntroductionTight junctions (TJs) serve as permeability filters between the internal and external cellular environment. A large number of proteins have been identified to be localized at the TJs. Due to limitations in tissue collection, TJs in the male genital tract have been understudied.MethodsWe analysed the transcriptomics of 132 TJ genes in foreskin tissue of men requesting voluntary medical male circumcision (VMMC) and enrolled in the Combined HIV Adolescent Prevention Study (CHAPS) trial conducted in South Africa and Uganda (NCT03986970). The trial evaluated the dose requirements for event-driven HIV pre-exposure prophylaxis (PrEP) with emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during insertive sex. A total of 144 participants were randomized to either control arm or one of 8 PrEP arms (n=16/arm), receiving oral FTC-TDF or FTC-TAF over one or two days. Following in vivo oral PrEP dosing and VMMC, the expression level of three important TJ proteins (CLDN-1, OCN and ZO-1) was measured ex vivo in foreskin tissue by Western blot. The expression of cytokine genes implicated in TJ regulation was determined. Non-parametric Kruskal-Wallis tests were used to compare TJ gene expression and protein levels by type of PrEP received, and Spearman’s correlation coefficients were calculated to assess whether TJ gene expression levels were related to cytokine gene levels or to PrEP drug concentrations and their active intracellularly phosphorylated metabolites.ResultsA high level of expression in foreskin tissue was found for 118 (of 132) TJ genes analysed; this finding contributed to create a map of TJ components within the male genital tract. Importantly, PrEP regimens tested in the CHAPS trial did not affect the expression of TJ genes and the analysed proteins in the foreskin; thus, further supporting the safety of this prevention strategy against HIV-1 transmission during insertive sex. Additionally, we identified the level of several cytokines’ genes to be correlated to TJ gene expression: among them, IL-18, IL-33 and VEGF.DiscussionTJs can limit viral entry into target cells; to affect this biological function viruses can reduce the expression of TJ proteins. Our study, on the expression and regulation of TJs in the foreskin, contribute important knowledge for PrEP safety and further design of HIV-1 prophylaxis.

Abstract Background Approximately 1.3 billion people worldwide face barriers in accessing inclusive healthcare due to disabilities, leading to worse health outcomes, particularly in low and middle-income countries (LMIC). However, there is a lack of training of healthcare workers about disability, both globally and in Uganda. Objectives To use mixed research methods to develop a comprehensive training program with standardisedelements for healthcare workers in Uganda, focusing on improving their knowledge, attitudes, and skills inproviding care for people with disabilities. Methods The Medical Research Council (MRC) approach was employed to guide the development of the training intervention. We conducted an umbrella review to gather relevant literature on disability training for healthcare workers. Interviews were conducted with international experts to gain insights and perspectives on the topic. Additionally, interviews were undertaken with people with disabilities and healthcare workers in Uganda to understand their experiences and needs. A participatory workshop was organised involving key stakeholders, to collaboratively design the training material based on the findings from these data sources. Results Eight review articles examined training programs for healthcare workers on disability. Training settings ranged from specialised clinical settings to non-clinical settings, and the duration and evaluation methods of the training varied widely. Lectures and didactic methods were commonly used, often combined with other approaches such as case studies and simulations. The impact of the training was assessed through healthcare worker reports on attitudes, knowledge, and self-efficacy. Interviews emphasised the importance of involving people with disabilities in the training and improving communication and understanding between healthcare providers and people with disabilities. Five themes for a training on disability for healthcare workers were generated through the workshop, including responsibilities and rights, communication, informed consent, accommodation, and referral and connection, which were used to guide the development of the curriculum, training materials and training approach. Conclusion This study presents a novel approach to develop a training program that aims to enhance healthcare services for people with disabilities in Uganda. The findings offer practical insights for the development of similar programs in LMICs. The effectiveness of the training program will be evaluated through a pilot test, and policy support is crucial for its successful implementation at scale.

Objectives Locally led research on cancer is needed in sub-Saharan Africa to set feasible research priorities that inform national policy. The aim of this project was to develop a research agenda for national cancer control planning, using a nationally driven approach, focused on barriers to diagnosis and high-quality treatment for prostate cancer in Zambia.Methods and analysis This was a Delphi process. 29 stakeholders were scored barriers on feasibility, the proportion of patients affected, the impact on patient outcomes and if there was a potential to address health systems barriers meaningfully. There were three rounds (R) to the process: (R1 and R2) by electronic survey and (R3) in-person meeting. In R1 statements scoring above 15 from over 70% of participants were prioritised immediately for R3 discussion. Those scoring below 30% were dropped and those in between were re-surveyed in R2.Results 22 and 17 of the 29 stakeholders responded to R1 and R2. 14 stakeholders attended R3. National priority research areas for prostate cancer in Zambia were identified as prostate cancer awareness; building affordable high-quality diagnostic capacity; affordability of specialist cancer treatments; supporting better access to medicines; delivery and coordination of services across the pathway and staff training.Conclusion The suggested seven priority areas allow for the development of the prostate cancer control programme to be conducted in a holistic manner. The expectation is with this guidance international partners can contribute within the frameworks of the local agenda for sustainable development to be realised.

Abstract Background There is little research on alcohol and other drugs (AOD) use by school-age children in low-resource settings like Uganda. Including the voices of children in research can inform prevention and early intervention efforts for those at risk of AOD use. The aim of this study was to understand the perspectives of children aged 6 to 13 years regarding AOD in Uganda. Methods This qualitative study was conducted in Mbale district, Uganda from February to March 2020. Eight focus group discussions (FGDs) were conducted with 56 primary school-age children, stratified by age (6–9 and 10–13 years), sex (male and female), and school status (in school and out of school). All FGDs were conducted in either Lumasaaba or Luganda. The FGDs were audio-recorded, transcribed verbatim, and translated into English. Data were coded, and overarching themes were identified using thematic framework analysis. Results Two themes identified were (1) Children’s perceptions and experiences with AODs. The participants understood alcohol by its consistency, colour, odour, and by brand/logo. They described the types and quantities of AOD consumed by school-age children, brewing processes for homemade alcoholic drinks, and short and long-term consequences of the use of alcohol. (2) Contributing factors to childhood drinking included: Stress relief for children who experienced multiple adversities (orphaned, poverty-stricken, and hailing from broken homes), fitting in with friends, influence from families, and media exposure that made alcohol look cool. Children would start drinking at an early age) or were given alcohol by their parents, sometimes before they could start talking. In the community, alcohol and other drugs were cheap and available and children could drink from anywhere, including in the classroom. Conclusions Children eligible for primary education in Uganda can easily access and use AOD. Several factors were identified as contributing to alcohol and other drug use among children, including availability and accessibility, advertising, lack of parental awareness and supervision, peer influence, adverse childhood experiences, socioeconomic factors, and cultural norms. There is a need for multi-sectoral action for awareness of childhood AOD use and deliberate consideration of children in the planning, design, and implementation of research, policies, and programs for prevention and early intervention.

Abstract Asthma is the most common chronic respiratory disease among school-going adolescents worldwide. However, the burden of severe asthma is highest in Sub-Saharan Africa. This study aimed to explore teachers’ perceptions of asthma care across six African countries. We conducted focus group discussions (FGDs) using a semi-structured interview guide. Interviews were audio-recorded, transcribed verbatim and analysed thematically. FGDs were conducted in Kumasi(Ghana), Blantyre (Malawi), Lagos (Nigeria), Durban (South Africa), Kampala (Uganda), and Harare (Zimbabwe) between 01 November 2020 and 30 June 2021. We identified two key themes related to asthma care; barriers to asthma care and suggestions to improve the care of adolescents with asthma. Barriers reported by teachers included a lack of knowledge and skills among themselves, adolescents, and caregivers. In addition, some traditional beliefs of teachers on asthma exacerbated challenges with asthma care in schools. Regarding suggestions, most teachers identified a need for all-inclusive asthma training programmes for teachers, adolescents and caregivers, focusing on acute episodes and mitigating triggers. Utilising teachers with personal experiences with asthma to advocate and support these initiatives was suggested. Further suggestions included the need for annual screening to enable early identification of adolescents with asthma and clarify restrictions on teachers administering asthma medications. Teachers across African schools identify multiple barriers to asthma care. Structured school education programs and annual asthma screening are key to addressing some barriers to care.

BackgroundA 12-dose, once-weekly regimen of isoniazid and rifapentine (3HP) is effective in preventing tuberculosis (TB) among people living with HIV (PLHIV). We sought to identify potential barriers to and facilitators of acceptance and completion of 3HP treatment from the perspective of people living with HIV (PLHIV) and health workers in a routine HIV care setting in Kampala, Uganda.MethodsWe conducted semi-structured interviews with 25 PLHIV and 10 health workers at an HIV/AIDS clinic in Kampala, Uganda. For both groups, we explored their understanding and interpretations of TB and TB preventive therapy (TPT), and perceptions about social and contextual factors that might influence the willingness of PLHIV to initiate and complete 3HP. We analyzed the data using an inductive thematic approach and aligned the emergent themes to the Behavior Change Wheel framework to identify sources of behavior and targeted behavior change interventions.ResultsFacilitators of acceptance and completion of 3HP treatment among PLHIV were fear of contracting TB, awareness of being at risk of getting TB, willingness to take TPT, trust in health workers, and the perceived benefits of directly observed therapy (DOT) and self-administered therapy (SAT) 3HP delivery strategies. Barriers included inadequate understanding of TPT, fear of potential side effects, concerns about the effectiveness of 3HP, and the perceived challenges of DOT or SAT. Among health workers, perceived facilitators included knowledge that TB is a common cause of mortality for PLHIV, fear of getting TB, and trust in the health workers by PLHIV, the advantages of once-weekly 3HP dosing, and the benefits of DOT and SAT 3HP delivery strategies. Health worker-reported barriers for PLHIV included inadequate understanding of TB and benefits of TPT, TB-associated stigma, potential side effects pill burden, and challenges of DOT and SAT 3HP delivery strategies. Lack of experience in the use of digital technology to monitor patient care was identified as a health worker-specific barrier. Identified intervention functions to address the facilitators or barriers included education, persuasion, environmental restructuring, enablement, and training.ConclusionsUsing a formative qualitative and comprehensive theoretical approach, we identified key barriers, facilitators, and appropriate interventions, including patient education, enhancing trust, and patient-centered treatment support that could be used to optimize the delivery of 3HP to PLHIV in our setting. These interventions are likely generalizable to other clinical interventions in similar populations in sub-Saharan Africa and other TB high-burden settings.

Abstract Background Malaria affects 24 million children globally, resulting in nearly 500,000 child deaths annually in low- and middle-income countries (LMICs). Recent studies have provided evidence that severe malaria infection results in sustained impairment in cognition and behaviour among young children; however, a formal meta-analysis has not been published. The objective was to assess the association between severe malaria infection with cognitive and behavioural outcomes among children living in LMICs. Methods Six online bibliographic databases were searched and reviewed in November 2022. Studies included involved children

The study aimed to assess the attitudes of stakeholders towards the use of unmanned aerial vehicles (medical drones) for delivering antiretroviral therapy (ART) in the Kalangala district of Uganda, which is comprised of 84 islands and has approximately 18,500 People Living with HIV (PLHIV). A qualitative baseline study was conducted to assess the acceptability and feasibility of using a medical drone for ART delivery in the island settlements of Kalangala Islands. The data revealed four emerging themes: knowledge about the drones, perceived benefits of medical drone delivery, perceived risks of medical drone use, and recommendations for future use. The study found that most participants, especially healthcare workers and key opinion leaders, were aware of the medical drones, which could reduce transport costs, deliver medication on time, and reduce healthcare workers' workload. However, there were also perceived risks related to the use of medical drones, such as stigma, reduced contact with healthcare providers, and maintenance and security issues. The study provided evidence that medical drones would be acceptable and have support from various stakeholders in the island settlements for ART delivery. However, concerns were raised about potential stigma and less health worker interaction. This qualitative work allowed the team to address these concerns during the pilot phase.

BackgroundRecently, a 3-month (12-dose) regimen of weekly isoniazid and rifapentine (3HP) was recommended by the World Health Organization for the prevention of tuberculosis (TB) among people living with HIV (PLHIV) on common antiretroviral therapy regimens. The best approach to delivering 3HP to PLHIV remains uncertain.MethodsWe developed a three-armed randomized trial assessing optimized strategies for delivering 3HP to PLHIV. The trial will be conducted at the Mulago Immune Suppression Syndrome (i.e., HIV/AIDS) clinic in Kampala, Uganda. We plan to recruit 1656 PLHIV, randomized 1:1 to each of the three arms (552 per arm). Using a hybrid type 3 effectiveness-implementation design, this pragmatic trial aims to (1) compare the acceptance and completion of 3HP among PLHIV under three delivery strategies: directly observed therapy (DOT), self-administered therapy (SAT), and informed patient choice of either DOT or SAT (with the assistance of a decision aid); (2) to identify processes and contextual factors that influence the acceptance and completion of 3HP under each delivery strategy; and (3) to estimate the costs and compare the cost-effectiveness of three strategies for delivering 3HP. The three delivery strategies were each optimized to address key barriers to 3HP completion using a theory-informed approach. We hypothesize that high levels of treatment acceptance and completion can be achieved among PLHIV in sub-Saharan Africa and that offering PLHIV an informed choice between the optimized DOT and SAT delivery strategies will result in greater acceptance and completion of 3HP. The design and planned evaluation of the delivery strategies were guided by the use of implementation science conceptual frameworks.Discussion3HP-one of the most promising interventions for TB prevention-will not be scaled up unless it can be delivered in a patient-centered fashion. We highlight shared decision-making as a key element of our trial design and theorize that offering PLHIV an informed choice between optimized delivery strategies will facilitate the highest levels of treatment acceptance and completion.Trial registrationClinicalTrials.gov: NCT03934931 ; Registered 2 May 2019.

Objective To identify key areas for research in prostate cancer (PC) in the Ugandan context by establishing the major health system, socioeconomic and clinical barriers to seeking, reaching and receiving high-quality cancer care.Design Modified Delphi Technique.Setting Government and private-not-for-profit hospitals.Methods We applied a two-stage modified Delphi technique to identify the consensus view across cancer experts. In round 1, experts received a questionnaire containing 21 statements drawn from a systematic review identifying the reason for the delay in accessing cancer care. Each statement was scored out of 20. Statements scoring ≥15 from over 70% of participants were prioritised for inclusion while statements for which

The penile epithelial microbiome remains underexplored. We sequenced human RNA and a segment of the bacterial 16S rRNA gene from the foreskin tissue of 144 adolescents from South Africa and Uganda collected during penile circumcision after receipt of 1–2 doses of placebo, emtricitabine + tenofovir disoproxil fumarate, or emtricitabine + tenofovir alafenamide to investigate the microbiome of foreskin tissue and its potential changes with antiretroviral use. We identified a large number of anaerobic species, including Corynebacterium acnes, which was detected more frequently in participants from South Africa than Uganda. Bacterial populations did not differ by treatment received, and no differentially abundant taxa were identified between placebo versus active drug recipients. The relative abundance of specific bacterial taxa was negatively correlated with expression of genes downstream of the innate immune response to bacteria and regulation of inflammation. Our results show no difference in the tissue microbiome of the foreskin with short-course antiretroviral use but that bacterial taxa were largely inversely correlated with inflammatory gene expression, consistent with commensal colonization.

Introduction On average, people with disabilities face many difficulties in accessing healthcare and experience worse health outcomes. Yet, evidence on how to overcome these barriers is lacking. Participatory approaches are gaining prominence as they can generate low-cost, appropriate and scalable solutions. This study protocol is for the pilot testing of the co-created Participatory Learning and Action for Disability (PLA-D) groups to assess feasibility.Methods and analysis We will pilot test PLA-D in five groups in Luuka district, Uganda during 2023. Each group will include approximately 20 members (people with disabilities, family members, carers) who will meet every 2–3 weeks over a 9–11 month period. The groups, guided by a trained facilitator, will identify issues about health and healthcare access and plan and implement locally generated solutions (eg, raising awareness of rights, advocacy and lobbying, establishing health savings and financing schemes). We will collect diverse sources of data to assess feasibility: (1) in-depth interviews and focus group discussions with group participants, non-participants and group facilitators; (2) monitoring of group activities; (3) direct observation of groups and (4) quantitative survey of group participants at baseline and endline. Data analyses will be undertaken to assess feasibility in terms of: acceptability, demand, implementation and practicality. We will develop and refine evaluation tools in preparation for a future trial.Ethics and dissemination Ethical approval for the study has been received by the London School of Hygiene & Tropical Medicine and the Uganda Virus Research Institute ethics committees. Informed consent will be obtained from all study participants, making adaptations for people with disabilities as necessary. We will reach different groups for our dissemination activities, including (1) people with disabilities (eg, community meetings); (2) policy and programme stakeholders in Uganda and international (eg, individual meetings, evidence briefs) and (3) academics (journal articles, conference/seminar presentations).

Objectives This study identifies barriers and provides recommendations to improve asthma care in children across sub-Saharan Africa, where qualitative data is lacking despite high rates.Design One of the aims of our National Institute for Health Research global health research group ‘Achieving Control of Asthma in Children in Africa’ was to use qualitative thematic analysis of transcribed audio recordings from focus group discussions (FGDs) to describe barriers to achieving good asthma control.Setting Schools in Blantyre (Malawi), Lagos (Nigeria), Durban (South Africa), Kampala (Uganda) and Harare (Zimbabwe).Participants Children (n=136), 12–14 years with either asthma symptoms or a diagnosis and their caregivers participated in 39 FGDs. All were recruited using asthma control questions from the Global Asthma Network survey.Results There were four key themes identified: (1) Poor understanding, (2) difficulties experienced with being diagnosed, (3) challenges with caring for children experiencing an acute asthma episode and (4) suboptimal uptake and use of prescribed medicines. An inadequate understanding of environmental triggers, a hesitancy in using metred dose inhalers and a preference for oral and alternate medications were identified as barriers. In addition, limited access to healthcare with delays in diagnosis and an inability to cope with expected lifestyle changes was reported. Based on these findings, we recommend tailored education to promote access to and acceptance of metred dose inhalers, including advocating for access to a single therapeutic, preventative and treatment option. Furthermore, healthcare systems should have simpler diagnostic pathways and easier emergency access for asthma.Conclusions In a continent with rapidly increasing levels of poorly controlled asthma, we identified multiple barriers to achieving good asthma control along the trajectory of care. Exploration of these barriers reveals several generalisable recommendations that should modify asthma care plans and potentially transform asthma care in Africa.Trial registration number 269211.

Abstract Background Menstrual health is an increasingly recognised public health issue, defined as complete physical, mental, and social well-being in relation to the menstrual cycle. The MENISCUS trial aims to assess whether a multi-component intervention addressing physical and emotional aspects of menstrual health improves educational attainment, mental health problems, menstrual management, self-efficacy, and quality of life among girls in secondary school in Uganda. Methods The study is a parallel-arm cluster-randomised controlled trial with 60 schools (clusters) in Wakiso and Kalungu districts, with a mixed-methods process evaluation to assess intervention fidelity and acceptability and economic and policy analyses. The schools will be randomised 1:1 to immediate intervention or to optimised usual care with delayed intervention delivery. The intervention includes creation of a Menstrual Health Action Group at schools and NGO-led training of trainers on puberty education, development of a drama skit, delivery of a menstrual health kit including reusable pads and menstrual cups, access to pain management strategies including analgesics, and basic improvements to school water, sanitation, and hygiene facilities. Baseline data will be collected from secondary 2 students in 2022 (median age ~15.5 years), with endline after 1 year of intervention delivery (~3600 females and a random sample of ~900 males). The primary outcomes assessed in girls are (i) examination performance based on the Mathematics, English, and Biology curriculum taught during the intervention delivery (independently assessed by the Uganda National Examinations Board) and (ii) mental health problems using the Total Difficulties Scale of the Strengths and Difficulties 25-item questionnaire. Secondary outcomes are menstrual knowledge and attitudes in girls and boys and, in girls only, menstrual practices, self-efficacy in managing menstruation, quality of life and happiness, prevalence of urogenital infections, school and class attendance using a self-completed menstrual daily diary, and confidence in maths and science. Discussion The trial is innovative in evaluating a multi-component school-based menstrual health intervention addressing both physical and emotional aspects of menstrual health and using a “training of trainers” model designed to be sustainable within schools. If found to be cost-effective and acceptable, the intervention will have the potential for national and regional scale-up. Trial registration ISRCTN 45461276 . Registered on 16 September 2021

Summary: Background: The efficacy of on-demand HIV pre-exposure prophylaxis (PrEP) for men in sub-Saharan Africa has not been evaluated, and the on-demand PrEP dosing requirement for insertive sex remains unknown. Methods: HIV-negative males 13–24 years, requesting voluntary medical male circumcision (VMMC), were enrolled into an open-label randomised controlled trial (NCT03986970), and randomised 1:1:1:1:1:1:1:1:1 to control arm or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) over one or two days, and circumcised 5 or 21 h thereafter. The primary outcome was foreskin p24 concentrations following ex vivo HIV-1BaL challenge. Secondary outcomes included peripheral blood mononuclear cell (PBMC) p24 concentration, and drug concentrations in foreskin tissue, PBMCs, plasma and foreskin CD4+/CD4-cells. In the control arm, post-exposure prophylaxis (PEP) activity of non-formulated tenofovir-emtricitabine (TFV-FTC) or TAF-FTC was assessed with ex vivo dosing 1, 24, 48 or 72 h post-HIV-1 challenge. Findings: 144 participants were analysed. PrEP with F/TDF or F/TAF prevented ex vivo infection of foreskins and PBMCs both 5 and 21 h after PrEP dosing. There was no difference between F/TDF and F/TAF (p24day15 geometric mean ratio 1.06, 95% confidence interval: 0.65–1.74). Additional ex vivo dosing did not further increase inhibition. In the control arm, PEP ex vivo dosing was effective up to 48 post-exposure diminishing thereafter, with TAF-FTC showing prolonged protection compared to TFV-FTC. Participants receiving F/TAF had higher TFV-DP concentrations in foreskin tissue and PBMCs compared with F/TDF, irrespective of dose and sampling interval; but F/TAF did not confer preferential TFV-DP distribution into foreskin HIV target cells. FTC-TP concentrations with both drug regimens were equivalent and ∼1 log higher than TFV-DP in foreskin. Interpretation: A double dose of either F/TDF or F/TAF given once either 5 or 21 h before ex vivo HIV-challenge provided protection across foreskin tissue. Further clinical evaluation of pre-coital PrEP for insertive sex is warranted. Funding: EDCTP2, Gilead Sciences, Vetenskapsrådet.

Abstract Introduction Cognitive impairment is common in first-episode psychosis patients and often associated with poor quality of life and functional impairment. However, most literature on this association is from high income countries and not low resource countries like Uganda. We aimed to determine the association between cognitive impairment with quality of life and functional impairment in Ugandan first-episode psychosis patients. Methods At Butabika national psychiatric hospital of Uganda, we enrolled 94 first-episode psychosis patients aged 18–60 years with a confirmed first-episode of psychosis and no previous treatment with antipsychotic medication. Neuropsychological assessment was performed using the MATRICS consensus cognitive battery (MCCB). Quality of life and functional impairment were assessed using the brief version of the World Health Organisation Quality of Life scale (WHOQOL-BREF) and the MINI International Neuropsychiatric Inventory (MINI) respectively. Linear regression analyses determined the association between impairment in different cognitive domains with various quality of life and functional impairment domains while controlling for age, gender and level of education. Results High scores in the reasoning and problem solving cognitive domain were associated with better quality of life in the psychological domain of WHOQOL-BREF (p = 0.029). For functional impairment, high cognitive scores in the domains of speed of processing (p = 0.018), reasoning and problem solving (p = 0.015), working memory (p = 0.017) and visual learning and memory (p = 0.002) were associated with psychosis “having a greater impact on other members of the family” on the MINI. Higher scores in the social cognition domain were associated with “less aggressive and disruptive behaviour” (p = 0.003). Conclusion Cognitive impairment in Ugandan first-episode psychotic patients is associated with both poorer quality of life and functional impairment. Remediation of cognitive function may be a plausible intervention to improve outcomes in Ugandan first-episode psychosis patients.

Objectives Late presentation and delays in diagnosis and treatment consistently translate into poor outcomes in sub-Saharan Africa (SSA). The aim of this study was to collate and appraise the factors influencing diagnostic and treatment delays of adult solid tumours in SSA.Design Systematic review with assessment of bias using Risk of Bias in Non-randomised Studies of Exposures (ROBINS-E) tool.Data sources PubMed and Embase, for publications from January 1995 to March 2021.Eligibility criteria Inclusion criteria: quantitative or mixed-method research, publications in English, on solid cancers in SSA countries. Exclusion criteria: paediatric populations, haematologic malignancies, and assessments of public perceptions and awareness of cancer (since the focus was on patients with a cancer diagnosis and treatment pathways).Data extraction and synthesis Two reviewers extracted and validated the studies. Data included year of publication; country; demographic characteristics; country-level setting; disease subsite; study design; type of delay, reasons for delay and primary outcomes.Results 57 out of 193 full-text reviews were included. 40% were from Nigeria or Ethiopia. 70% focused on breast or cervical cancer. 43 studies had a high risk of bias at preliminary stages of quality assessment. 14 studies met the criteria for full assessment and all totaled to either high or very high risk of bias across seven domains. Reasons for delays included high costs of diagnostic and treatment services; lack of coordination between primary, secondary and tertiary healthcare sectors; inadequate staffing; and continued reliance on traditional healers and complimentary medicines.Conclusions Robust research to inform policy on the barriers to quality cancer care in SSA is absent. The focus of most research is on breast and cervical cancers. Research outputs are from few countries. It is imperative that we investigate the complex interaction of these factors to build resilient and effective cancer control programmes.

Abstract Background It is not known whether post-traumatic stress disorder (PTSD) increases HIV-risk behaviours among young people in sub-Saharan Africa. We assessed associations of PTSD symptoms with sexual behaviour, HIV risk perception, and attitudes towards PrEP among young people taking part in the CHAPS community survey. We hypothesised that PTSD symptoms would increase sexual behaviours associated with HIV risk, hinder PrEP uptake and influence preference for daily versus on-demand PrEP. Methods Young people without HIV, aged 13–24 years, were purposively recruited in Johannesburg and Cape Town in South Africa, Wakiso in Uganda, and Chitungwiza in Zimbabwe, and surveyed on socio-demographic characteristics, PrEP knowledge and attitudes, sexual behaviour, HIV perception and salience, and mental health. PTSD symptoms were measured using the Primary Care PTSD Screen for the Diagnostic and Statistical Manual of Mental Disorders 5 (PC-PTSD-5). Logistic and ordinal logistic regression was used to assess associations between PC-PTSD-5 score and socio-demographic characteristics, sexual behaviour, HIV risk perception, PrEP attitudes, and substance use, adjusting for age, sex, setting, depression and anxiety. Results Of 1330 young people (51% male, median age 19 years), 522 (39%) reported at least one PTSD symptom. There was strong evidence that having a higher PC-PTSD-5 score was associated with reported forced sex (OR 3.18, 95%CI: 2.05–4.93), self-perception as a person who takes risks (OR 1.12, 95%CI: 1.04–1.20), and increased frequency of thinking about risk of HIV acquisition (OR 1.16, 95%CI: 1.08–1.25). PTSD symptoms were not associated with willingness to take PrEP, preference for on-demand versus daily PrEP, or actual HIV risk behaviour such as condomless sex. Conclusions Symptoms consistent with probable PTSD were common among young people in South Africa, Uganda and Zimbabwe but did not impact PrEP attitudes or PrEP preferences. Evaluation for PTSD might form part of a general assessment in sexual and reproductive health services in these countries. More work is needed to understand the impact of PTSD on HIV-risk behaviour, forced sex and response to preventive strategies including PrEP.

Introduction: Tight junctions (TJs) serve as permeability filters between the internal and external cellular environment. A large number of proteins have been identified to be localized at the TJs. Due to limitations in tissue collection, TJs in the male genital tract have been understudied. Methods: We analysed the transcriptomics of 132 TJ genes in foreskin tissue of men requesting voluntary medical male circumcision (VMMC) and enrolled in the Combined HIV Adolescent Prevention Study (CHAPS) trial conducted in South Africa and Uganda (NCT03986970). The trial evaluated the dose requirements for event-driven HIV pre-exposure prophylaxis (PrEP) with emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during insertive sex. A total of 144 participants were randomized to either control arm or one of 8 PrEP arms (n=16/arm), receiving oral FTC-TDF or FTC-TAF over one or two days. Following in vivo oral PrEP dosing and VMMC, the expression level of three important TJ proteins (CLDN-1, OCN and ZO-1) was measured ex vivo in foreskin tissue by Western blot. The expression of cytokine genes implicated in TJ regulation was determined. Non-parametric Kruskal-Wallis tests were used to compare TJ gene expression and protein levels by type of PrEP received, and Spearman's correlation coefficients were calculated to assess whether TJ gene expression levels were related to cytokine gene levels or to PrEP drug concentrations and their active intracellularly phosphorylated metabolites. Results: A high level of expression in foreskin tissue was found for 118 (of 132) TJ genes analysed; this finding contributed to create a map of TJ components within the male genital tract. Importantly, PrEP regimens tested in the CHAPS trial did not affect the expression of TJ genes and the analysed proteins in the foreskin; thus, further supporting the safety of this prevention strategy against HIV-1 transmission during insertive sex. Additionally, we identified the level of several cytokines' genes to be correlated to TJ gene expression: among them, IL-18, IL-33 and VEGF. Discussion: TJs can limit viral entry into target cells; to affect this biological function viruses can reduce the expression of TJ proteins. Our study, on the expression and regulation of TJs in the foreskin, contribute important knowledge for PrEP safety and further design of HIV-1 prophylaxis. [ABSTRACT FROM AUTHOR]

BackgroundAdolescents in sub-Saharan Africa (SSA) remain vulnerable to HIV infection. While pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV transmission as a daily or on-demand regimen, tailored approaches are necessary. The Combined HIV Adolescent PrEP and Prevention Study (CHAPS) is a mixed-methods research program investigating the acceptability and feasibility of implementing daily and on-demand PrEP among young people in SSA. It also aims to determine an on-demand dosing schedule for insertive sex. For this paper, we explored preferences for daily versus on-demand PrEP amongst adolescents as part of CHAPS.MethodsPurposive sampling was used to recruit participants from Soweto and Cape Town (South Africa), Wakiso district (Uganda) and Chitungwiza (Zimbabwe). At the time of the study in 2018/2019, Uganda had not rolled out PrEP to the general population; in Zimbabwe, PrEP for young people was only available at selected sites with one located within the study recruitment area. In South Africa, PrEP was made available to selected high-risk groups. We conducted 60 in-depth interviews and 24 group discussions amongst young people aged 13-24 without HIV in South Africa, Uganda, and Zimbabwe. All in-depth interviews and group discussions were audio-recorded, transcribed verbatim and translated to English. Data were analysed using framework analysis. The main themes were centered around preferences for daily and on-demand PrEP.ResultsReasons for on-demand preferences included stigma, pill fatigue, adherence and side effects. Reasons for daily PrEP preferences included factors related to sexual risk behaviour, continuous protection against incidents of unintentional exposure, and the increased efficacy of a daily dose. Participants at all sites preferring daily PrEP identified the same reasons, with more males than females citing inadvertent blood contact or perceived increased efficacy. Similarly, participants at all sites preferring on-demand PrEP gave the same reasons for their preferences for on-demand PrEP; the exception was South Africans who did not mention the hope of having fewer side effects by not taking daily PrEP. Additionally, more males than females cited intermittent sex as a reason for opting for on-demand PrEP.ConclusionsOur study is the first known to explore and describe youth preferences for daily versus on-demand PrEP. While the choice is clear-cut, the reasons cited in the different options provide invaluable insights into their decisions, and the actual and perceived facilitators and barriers to access to PrEP. Further education is needed amongst young people, not only about PrEP but also in other areas of comprehensive sexuality education. Exploring all options of HIV prevention is crucial to provide a tailored, one-size-does-not-fit-all approach to adolescent care in SSA to reduce and, the continued and increasing risk of this preventable infection.

BackgroundPreterm birth is associated with life-long cost implications on the infant, family, health system, and society at large. The costs related to lost productivity at contributions at work during care of preterm infants are difficult to measure. We aimed to explore and document the unpriced costs parents incur following birth of a preterm infant in the first year of life in a low resource setting.MethodsThirty-nine mothers and five fathers of preterm infants who had ever attended the preterm follow-up clinic after discharge from Mulago National Referral Hospital, were included in a qualitative study between November 2019 and February 2020. Participants were purposively selected, and data were collected using four focused group discussions with mothers and in-depth interviews with the fathers lasting 30-70 minutes each. These were audio-recorded, transcribed and translated. The data were manually analysed using the thematic approach.FindingsThree themes were generated: i) complex nature of the infant, ii) time to care for the infant, iii) mother as the predominant caregiver. The parents perceived preterm infants as delicate, complicated and their care more costly compared to those born at term. Expressions of need for time to care for their infants, frequent hospital visits and readmission were raised. Availability of the mother as the predominant caregiver some of whose roles cannot be delegated and their experiences following return to work after birth of a preterm were cited by the participants.ConclusionThe results highlight the unpriced costs incurred by the parents through disruption of the work pattern due to the actual and perceived needs of a preterm infant and time to care in a low resource setting. We recommend guidance on financial planning, development of policies and programs on social and financial support for parents and future studies on indirect costs of preterm care.

BackgroundHIV remains a leading contributor to the disease burden in sub-Saharan Africa, with adolescents and young people disproportionately affected. Optimising pre-exposure prophylaxis (PrEP) uptake has predominantly focused on women and adult men who have sex with men. We explore adolescent boys and young men's PrEP uptake preferences in South Africa, Uganda, and Zimbabwe.MethodsA cross-sectional sequential exploratory mixed-methods study amongst males aged 13-24 years was conducted between April and September 2019 as part of the CHAPS trial. Group discussions (GDs) and In-Depth Interviews (IDIs) focused on motivations and hindrances for HIV testing, PrEP preference, and reasons for the uptake of PrEP. A thematic approach was used to analyse the qualitative data. A quantitative survey following the qualitative work covered questions on demographics, HIV risk and PrEP preferences (on-demand vs. daily). For quantitative analysis, we fitted logistic regression models to determine factors associated with on-demand vs daily PrEP preference.ResultsOverall, 647 adolescent boys and young men (median age 20, IQR: 17-22) were enrolled. Of these, 422 (65.22%) preferred on-demand PrEP (South Africa 45.45%, Uganda 76.80%, Zimbabwe 70.35%; p24 hours in advance aOR = 1.4 (0.9-2.3) compared to ConclusionPreference for on-demand PrEP is high in young males. The qualitative data support a preference for on-demand PrEP in those who plan sex in advance. HIV intervention programs should offer both on-demand and daily PrEP to engage more adolescent boys and young men in HIV prevention practices.

Whilst short-term oral pre-exposure prophylaxis (PrEP) with antiretroviral drugs in men who have sex with men has shown protection against HIV-1 infection, the impact of this regimen on the in vivo foreskin transcriptome is unknown. We collected foreskin tissue after voluntary medical male circumcision from 144 young men (72 from Uganda and 72 from South Africa) randomized to one to two doses of either oral tenofovir (TFV) disoproxil fumarate (FTC-TDF) or tenofovir alafenamide (FTC-TAF) or no drug (untreated controls). This novel approach allowed us to examine the impact of short-term oral PrEP on transcriptome of the male genital tract. A single dose of FTC-TDF did not affect the foreskin transcriptome in relation to control arm, however one dose of FTC-TAF induced upregulation of four genes AKAP8, KIAA0141, HSCB and METTL17. Following two doses of either FTC-TDF or FTC-TAF, there was an increase in 34 differentially expressed genes for FTC-TDF and 15 for FTC-TAF, with nine DEGs in common: KIAA0141, SAFB2, CACTIN, FXR2, AKAP8, HSCB, CLNS1A, DDX27 and DCAF15. Functional analysis of differentially expressed genes revealed modulation of biological processes related to mitochondrial stress (KIAA0141, HSCB and METTL17), anti-viral and anti-inflammatory pathways (CACTIN and AKAP8). Our results show that short-course on-demand oral PrEP in men modulates genes in foreskin tissue which are likely unfavorable to HIV acquisition and replication. We also describe an upregulated expression of genes involved in diverse mitochondria biology which may potentially result in worsened mitochondria-related. These results warrant further studies to assess the role of short-course and prolonged oral PrEP on biological processes of the foreskin mucosa.

Abstract Background A 12-dose, once-weekly regimen of isoniazid and rifapentine (3HP) is effective in preventing tuberculosis (TB) among people living with HIV (PLHIV). We sought to identify potential barriers to and facilitators of acceptance and completion of 3HP treatment from the perspective of people living with HIV (PLHIV) and health workers in a routine HIV care setting in Kampala, Uganda. Methods We conducted semi-structured interviews with 25 PLHIV and 10 health workers at an HIV/AIDS clinic in Kampala, Uganda. For both groups, we explored their understanding and interpretations of TB and TB preventive therapy (TPT), and perceptions about social and contextual factors that might influence the willingness of PLHIV to initiate and complete 3HP. We analyzed the data using an inductive thematic approach and aligned the emergent themes to the Behavior Change Wheel framework to identify sources of behavior and targeted behavior change interventions. Results Facilitators of acceptance and completion of 3HP treatment among PLHIV were fear of contracting TB, awareness of being at risk of getting TB, willingness to take TPT, trust in health workers, and the perceived benefits of directly observed therapy (DOT) and self-administered therapy (SAT) 3HP delivery strategies. Barriers included inadequate understanding of TPT, fear of potential side effects, concerns about the effectiveness of 3HP, and the perceived challenges of DOT or SAT. Among health workers, perceived facilitators included knowledge that TB is a common cause of mortality for PLHIV, fear of getting TB, and trust in the health workers by PLHIV, the advantages of once-weekly 3HP dosing, and the benefits of DOT and SAT 3HP delivery strategies. Health worker-reported barriers for PLHIV included inadequate understanding of TB and benefits of TPT, TB-associated stigma, potential side effects pill burden, and challenges of DOT and SAT 3HP delivery strategies. Lack of experience in the use of digital technology to monitor patient care was identified as a health worker-specific barrier. Identified intervention functions to address the facilitators or barriers included education, persuasion, environmental restructuring, enablement, and training. Conclusions Using a formative qualitative and comprehensive theoretical approach, we identified key barriers, facilitators, and appropriate interventions, including patient education, enhancing trust, and patient-centered treatment support that could be used to optimize the delivery of 3HP to PLHIV in our setting. These interventions are likely generalizable to other clinical interventions in similar populations in sub-Saharan Africa and other TB high-burden settings.

HIV-1 pre-exposure prophylaxis (PrEP) relies on inhibition of HIV-1 replication steps. To understand how PrEP modulates the immunological environment, we derived the plasma proteomic profile of men receiving emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during the CHAPS trial in South Africa and Uganda (NCT03986970). The CHAPS trial randomized 144 participants to one control and 8 PrEP arms, differing by drug type, number of PrEP doses and timing from final PrEP dose to sampling. Blood was collected pre- and post-PrEP. The inflammatory profile of plasma samples was analyzed using Olink (N=92 proteins) and Luminex (N=33) and associated with plasma drug concentrations using mass spectrometry. The proteins whose levels changed most significantly from pre- to post-PrEP were CCL4, CCL3 and TNF-α; CCL4 was the key discriminator between pre- and post-PrEP samples. CCL4 and CCL3 levels were significantly increased in post-PrEP samples compared to control specimens. CCL4 was significantly correlated with FTC drug levels in plasma. Production of inflammatory chemokines CCL4 and CCL3 in response to short-term PrEP indicates the mobilization of ligands which potentially block virus attachment to CCR5 HIV-1 co-receptor. The significant correlation between CCL4 and FTC levels suggests that CCL4 increase is modulated as an inflammatory response to PrEP.