The over 14 million African children who are HIV-exposed but uninfected (CHEU) are at risk for poor health outcomes, including neurodevelopmental conditions such as autism; however, no study to date has examined autism in CHEU in Africa, where the vast majority of these children live. Scalable diagnostic and neurobehavioural tools, including powerful, low-cost approaches such as eye-tracking, for detection and study of mechanistic neural processes are necessary to advance autism research in these settings. The objective of this study is to examine autism diagnostic outcomes and eye-tracking biomarkers in relation to CHEU while at the same time building capacity for neuro-health research in Kenya.
This study will leverage a longitudinally assessed cohort of CHEU and children who are HIV-unexposed and uninfected (CHUU) with well characterised HIV-related and contextual exposures. We will first determine and compare autism diagnostic outcomes between young CHEU and CHUU across a large cohort (n=850) of Kenyan children using research-grade autism assessment tools, and, second, determine whether neurobehavioural eye-tracking markers predict autism outcomes across this cohort.
Human subjects approvals have been obtained from Moi University Institutional Review and Ethics Committee (IREC; IREC/909/2024; Approval #0004835), Kenya’s National Commission for Science, Technology and Innovation (NACOSTI; Reference #NACOSTI/P/25/415028), the Institutional Review Board of the Indiana University School of Medicine (Protocol #23171), with reliance agreements executed with Purdue University and Boston University. Dissemination of findings will occur through multiple channels within the research and clinical community, including peer-reviewed journal publications and conference abstracts and presentations. As part of capacity building efforts, the research team will also communicate study results to policy makers, the lay public and other health systems involved in the care of young children with disabilities via study-hosted workshops and conferences.
Cancer in adolescents and young adults (AYAs; ages 15–39 years) is a rising global epidemic. Yet, AYAs remain an understudied population, and little is known about what research topics should be prioritised according to those with lived experience. The AYA Cancer Priority Setting Partnership (PSP) was established to identify the top 10 research priorities for AYA cancer in Canada according to patients, caregivers, and clinicians.
This project followed the James Lind Alliance (JLA) Priority Setting Partnership (PSP) methodology that included two national cross-sectional surveys and a final priority setting workshop following an adapted nominal group technique.
A national sample was recruited to participate from across Canada.
Participants were patients, caregivers, and clinicians with lived personal and/or professional experience of AYA cancer in Canada.
In the first survey, open-ended responses were collected from participants about questions they would like answered by research. Responses were collated into overarching summary questions and a literature search was undertaken to verify if questions were true uncertainties and not fully answered by existing evidence. Unanswered questions were ranked by participants in a second survey. The top-ranked questions were prioritised through consensus at the final priority setting workshop. The final outcome was the top 10 priorities for AYA cancer research in Canada.
In the initial survey, 1916 potential research questions were submitted by 275 patients, caregivers, and clinicians. Following data processing, summary question formation, and the evidence check, 58 questions were put forward for interim prioritisation in a second survey (n=285 patients, caregivers, and clinicians). The top 20 questions from the interim prioritisation were ranked at the final priority setting workshop attended by a diverse group of 23 patients, caregivers and clinicians from across Canada. The resulting top 10 priorities reflect topics across the cancer continuum including: diagnostic delays, screening and early detection, novel therapies, psychosocial impacts, end-of-life concerns, and survivorship issues.
This patient-directed research agenda will guide researchers, funding agencies, and policymakers to ensure that future research is aligned with what matters most to the AYA cancer community.
To test the agreement and usability of a novel quality appraisal tool: A MeaSurement Tool to Assess systematic Reviews of Prognostic Factor studies (AMSTAR-PF).
Observational study.
14 appraisers of varied experience levels and backgrounds, including undergraduate, master’s and PhD students, postgraduate researchers, research fellows and clinicians.
Eight systematic reviews were rated by all reviewers using AMSTAR-PF.
Planned measures included intrapair and inter-pair agreement using Cohen’s and Fleiss’ kappa, time of use and time to reach consensus. Interrater agreement was an added measure, and Gwet’s agreement coefficient was calculated and presented due to its greater stability across agreement levels. The percentage of intrapair agreements identical or one category apart was also presented.
Interrater agreement averaged 0.59 (range 0.21–0.90), inter-pair agreement 0.61 (range 0.24–0.91) and intrapair agreement 0.75 (range 0.45–0.95) across the domains, with agreement for the overall rating 0.46 (95% CI 0.30 to 0.62) for interrater agreement, 0.46 (95% CI 0.17 to 0.74) for inter-pair agreement and 0.68 (range of averages 0.22–1.00) for intrapair agreement. The majority (60.7%) of intrapair ratings were identical, with 94.6% of final ratings either identical or only one category different for the overall appraisal. The time taken to appraise a study with AMSTAR-PF improved with use and averaged around 34 min after the first two appraisals.
Despite some variance in agreement for different domains and between different appraisers, the testing results suggest that AMSTAR-PF has clear utility for appraising the quality of systematic reviews of prognostic factor studies.
Women who develop gestational diabetes mellitus (GDM) have a 60% lifetime risk of developing type 2 diabetes mellitus (T2D), which is already elevated within the first decade following childbirth. Despite the impact of lifestyle interventions to reduce long-term T2D risk in women with previous GDM, successful implementation of lifestyle interventions remains a barrier. Metformin is recommended for adults at increased risk of developing T2D; however, there is limited evidence of tolerability in the early postpartum period. Glucagon-like peptide 1 receptor agonists (GLP-1 RA) are effective at improving glycaemic status and body weight. However, GLP-1 RA have not been evaluated in the postpartum population. Finally, physical activity monitors may support behaviour changes related to physical activity to reduce long-term risk of T2D but are yet to be studied following GDM.
This will be a multicentre, randomised, open-label interventional pilot study. Using a 2x2 factorial design, we will examine the feasibility and acceptability of a pharmacotherapy intervention and a physical activity intervention in women with previous GDM at increased risk of developing T2D. Participants will be recruited from tertiary referral hospitals in Australia and will be randomised to receive either metformin alone or in combination with a GLP-1 RA and subsequently randomised to either a physical activity intervention involving activity monitor use, or usual care for 6 months, followed by a 6-month follow-up period. Primary feasibility outcomes include the acceptability and safety of the metformin and GLP-1 RA as measured through pill and injection counts, acceptability questionnaire and adverse events.
This trial is registered with the Australian and New Zealand Clinical Trials Registry (Registration Number: ACTRN12624001253594). This trial has received ethics approval from the South Eastern Sydney Local Health District Human Research Ethics Committee (Approval Number: 2024/ETH00042, protocol version v1.1, 28/02/2025).
Australian and New Zealand Clinical Trials Registry, Registration Number: ACTRN12624001253594.