YouBelong Home: A Ugandan Community Mental Health Intervention

In Uganda, low resources for mental health provision combine with disadvantage and inadequate supports for family and community-based care. Catalysed by the need to reduce overcrowded psychiatric hospital wards and frequent readmissions at Butabika National Referral Mental Hospital (BNRMH) in Kampala, the nongovernment organisation YouBelong Uganda (YBU) developed the YouBelong Home (YBH) intervention. YBH is a theoretically eclectic pre and post hospital discharge intervention. This paper reports on qualitative findings of the project Curtailing Hospital Readmissions for Patients with Severe Mental Illness in Africa (CHaRISMA), which explored how to refine the YBH intervention. The project was funded by a UK Joint Global Health Trials (JGHT) Development Grant. Data was collected through structured interviews with service users and caregivers, reflective practice by the YBH implementing team and a stakeholder focus group. A summary of refinements to the YBH intervention follows the TIDieR format (Template for Intervention Description and Replication)

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Establishing a library of resources to help people understand key concepts in assessing treatment claims—The “Critical thinking and Appraisal Resource Library” (CARL)

Background People are frequently confronted with untrustworthy claims about the effects of treatments. Uncritical acceptance of these claims can lead to poor, and sometimes dangerous, treatment decisions, and wasted time and money. Resources to help people learn to think critically about treatment claims are scarce, and they are widely scattered. Furthermore, very few learning-resources have been assessed to see if they improve knowledge and behavior. Objectives Our objectives were to develop the Critical thinking and Appraisal Resource Library (CARL). This library was to be in the form of a database containing learning resources for those who are responsible for encouraging critical thinking about treatment claims, and was to be made available online. We wished to include resources for groups we identified as ‘intermediaries’ of knowledge, i.e. teachers of schoolchildren, undergraduates and graduates, for example those teaching evidence-based medicine, or those communicating treatment claims to the public. In selecting resources, we wished to draw particular attention to those resources that had been formally evaluated, for example, by the creators of the resource or independent research groups. Methods CARL was populated with learning-resources identified from a variety of sources—two previously developed but unmaintained inventories; systematic reviews of learning-interventions; online and database searches; and recommendations by members of the project group and its advisors. The learning-resources in CARL were organised by ‘Key Concepts’ needed to judge the trustworthiness of treatment claims, and were made available online by the James Lind Initiative in Testing Treatments interactive (TTi) English (www.testingtreatments.org/category/learning-resources).TTi English also incorporated the database of Key Concepts and the Claim Evaluation Tools developed through the Informed Healthcare Choices (IHC) project (informedhealthchoices.org). Results We have created a database of resources called CARL, which currently contains over 500 open-access learning-resources in a variety of formats: text, audio, video, webpages, cartoons, and lesson materials. These are aimed primarily at ‘Intermediaries’, that is, ‘teachers’, ‘communicators’, ‘advisors’, ‘researchers’, as well as for independent ‘learners’. The resources included in CARL are currently accessible at www.testingtreatments.org/category/learning-resources Conclusions We hope that ready access to CARL will help to promote the critical thinking about treatment claims, needed to help improve healthcare choices

Development and validation of quantitative PCR assays for HIV-associated cryptococcal meningitis in sub-Saharan Africa: a diagnostic accuracy study

Background: HIV-associated cryptococcal meningitis is the second leading cause of AIDS-related deaths, with a 10-week mortality rate of 25–30%. Fungal load assessed by colony-forming unit (CFU) counts is used as a prognostic marker and to monitor response to treatment in research studies. PCR-based assessment of fungal load could be quicker and less labour-intensive. We sought to design, optimise, and validate quantitative PCR (qPCR) assays for the detection, identification, and quantification of Cryptococcus infections in patients with cryptococcal meningitis in sub-Saharan Africa. Methods: We developed and validated species-specific qPCR assays based on DNA amplification of QSP1 (QSP1A specific to Cryptococcus neoformans, QSP1B/C specific to Cryptococcus deneoformans, and QSP1D specific to Cryptococcus gattii species) and a pan-Cryptococcus assay based on a multicopy 28S rRNA gene. This was a longitudinal study that validated the designed assays on cerebrospinal fluid (CSF) of 209 patients with cryptococcal meningitis at baseline (day 0) and during anti-fungal therapy (day 7 and day 14), from the AMBITION-cm trial in Botswana and Malawi (2018–21). Eligible patients were aged 18 years or older and presenting with a first case of cryptococcal meningitis. Findings: When compared with quantitative cryptococcal culture as the reference, the sensitivity of the 28S rRNA was 98·2% (95% CI 95·1–99·5) and of the QSP1 assay was 90·4% (85·2–94·0) in CSF at day 0. Quantification of the fungal load with QSP1 and 28S rRNA qPCR correlated with quantitative cryptococcal culture (R2=0·73 and R2=0·78, respectively). Both Botswana and Malawi had a predominant C neoformans prevalence of 67% (95% CI 55–75) and 68% (57–73), respectively, and lower C gattii rates of 21% (14–31) and 8% (4–14), respectively. We identified ten patients that, after 14 days of treatment, harboured viable but non-culturable yeasts based on QSP1 RNA detection (without any positive CFU in CSF culture). Interpretation: QSP1 and 28S rRNA assays are useful in identifying Cryptococcus species. qPCR results correlate well with baseline quantitative cryptococcal culture and show a similar decline in fungal load during induction therapy. These assays could be a faster alternative to quantitative cryptococcal culture to determine fungal load clearance. The clinical implications of the possible detection of viable but non-culturable cells in CSF during induction therapy remain unclear. Funding: European and Developing Countries Clinical Trials Partnership; Swedish International Development Cooperation Agency; Wellcome Trust/UK Medical Research Council/UKAID Joint Global Health Trials; and UK National Institute for Health Research

Development and validation of quantitative PCR assays for HIV-associated cryptococcal meningitis in sub-Saharan Africa: a diagnostic accuracy study

Background: HIV-associated cryptococcal meningitis is the second leading cause of AIDS-related deaths, with a 10-week mortality rate of 25–30%. Fungal load assessed by colony-forming unit (CFU) counts is used as a prognostic marker and to monitor response to treatment in research studies. PCR-based assessment of fungal load could be quicker and less labour-intensive. We sought to design, optimise, and validate quantitative PCR (qPCR) assays for the detection, identification, and quantification of Cryptococcus infections in patients with cryptococcal meningitis in sub-Saharan Africa. Methods: We developed and validated species-specific qPCR assays based on DNA amplification of QSP1 (QSP1A specific to Cryptococcus neoformans, QSP1B/C specific to Cryptococcus deneoformans, and QSP1D specific to Cryptococcus gattii species) and a pan-Cryptococcus assay based on a multicopy 28S rRNA gene. This was a longitudinal study that validated the designed assays on cerebrospinal fluid (CSF) of 209 patients with cryptococcal meningitis at baseline (day 0) and during anti-fungal therapy (day 7 and day 14), from the AMBITION-cm trial in Botswana and Malawi (2018–21). Eligible patients were aged 18 years or older and presenting with a first case of cryptococcal meningitis. Findings: When compared with quantitative cryptococcal culture as the reference, the sensitivity of the 28S rRNA was 98·2% (95% CI 95·1–99·5) and of the QSP1 assay was 90·4% (85·2–94·0) in CSF at day 0. Quantification of the fungal load with QSP1 and 28S rRNA qPCR correlated with quantitative cryptococcal culture (R2=0·73 and R2=0·78, respectively). Both Botswana and Malawi had a predominant C neoformans prevalence of 67% (95% CI 55–75) and 68% (57–73), respectively, and lower C gattii rates of 21% (14–31) and 8% (4–14), respectively. We identified ten patients that, after 14 days of treatment, harboured viable but non-culturable yeasts based on QSP1 RNA detection (without any positive CFU in CSF culture). Interpretation: QSP1 and 28S rRNA assays are useful in identifying Cryptococcus species. qPCR results correlate well with baseline quantitative cryptococcal culture and show a similar decline in fungal load during induction therapy. These assays could be a faster alternative to quantitative cryptococcal culture to determine fungal load clearance. The clinical implications of the possible detection of viable but non-culturable cells in CSF during induction therapy remain unclear

Protocol for assessing stakeholder engagement in the development and evaluation of the Informed Health Choices resources teaching secondary school students to think critically about health claims and choices.

BackgroundAs part of a five year plan (2019-2023), the Informed Health Choices Project, is developing and evaluating resources for helping secondary school students learn to think critically about health claims and choices. We will bring together key stakeholders; such as secondary school teachers and students, our main target for the IHC secondary school resources, school administrators, policy makers, curriculum development specialists and parents, to enable us gain insight about the context.ObjectivesTo ensure that stakeholders are effectively and appropriately engaged in the design, evaluation and dissemination of the learning resources.To evaluate the extent to which stakeholders were successfully engaged.MethodsUsing a multi-stage stratified sampling method, we will identify a representative sample of secondary schools with varied characteristics that might modify the effects of the learning resources such as, the school location (rural, semi-urban or urban), ownership (private, public) and ICT facilities (under resourced, highly resourced). A sample of schools will be randomly selected from the schools in each stratum. We will aim to recruit a diverse sample of students and secondary school teachers from those schools. Other stakeholders will be purposively selected to ensure a diverse range of experience and expertise.ResultsTogether with the teacher and student networks and the advisory panels, we will establish measurable success criteria that reflect the objectives of engaging stakeholders at the start of the project and evaluate the extent to which those criteria were met at the end of the project.ConclusionWe aim for an increase in research uptake, improve quality and appropriateness of research results, accountability and social justice