Climate change has led to extreme heat events, disproportionately affecting vulnerable populations. Heat stress during pregnancy is linked to adverse health outcomes, yet the biological mechanisms remain poorly understood. This research study aims to investigate the effect of environmental heat on maternal, fetal and infant health and examine the biological pathways linking heat stress to adverse pregnancy outcomes.

This prospective cohort study will recruit 6000 pregnant women from three districts in Sindh, Pakistan. Eligible participants ≥18 years old, will have a minimum of five scheduled visits from

The study has received ethical approval from the Aga Khan University (AKU) (Ref: 26249) and the Pakistan National Bioethics Committee (Ref: 1065/23/1736). Written informed consent will be obtained from all participants before enrolment. Referral pathways to healthcare facilities will be established to ensure timely management of pregnancy complications. Findings will be disseminated through peer-reviewed publications, scientific conferences, and engagement with policymakers and public health stakeholders to inform climate-resilient maternal health strategies. Results will also be shared with participants and communities through meetings and informal sessions to raise awareness and support evidence-based heat adaptation.

NCT01234567.

Peripheral artery disease (PAD) affected approximately 800 000 Canadians aged 25 years or older in 2015 and it poses a substantial risk of lower extremity amputation (LEA). While clinical risk factors for amputation are well-established, the impact of social determinants of health (SDoH) on amputation risk remains unclear, particularly in a Canadian context.

This systematic review aims to: (1) synthesise evidence on the associations between multilevel SDoH domains and LEA (both major and/or minor) risk in Canadian PAD patients including intersectional effects of race and ethnicity with another SDoH domain, and (2) evaluate the statistical methodologies used in the researched literature to inform future study design and analysis approaches.

We will systematically search MEDLINE, Embase, EmCare, Global Health, Cumulative Index to Nursing and Allied Health Literature and Web of Science for studies examining SDoH and LEA in Canadian patients with PAD (including chronic limb-threatening ischaemia which is a severe form of PAD). Date limits for each database will be from inception through December 2025. SDoH will be categorised using a modified Healthy People 2030 SDoH framework under six domains: economic stability, education, food, neighbourhood and physical environment, healthcare system and community and social context. Two reviewers will independently screen titles, abstracts and full texts, with discrepancies resolved by a third reviewer. Data will be extracted on study characteristics, SDoH measures, outcomes and statistical methods. Risk of bias will be assessed using RoB 2 for randomised trials, ROBINS-I for non-randomised studies of interventions and ROBINS-E for studies investigating exposures. A narrative synthesis, and where data permit, a Bayesian hierarchical meta-analysis using both effect size and contingency table approaches will be conducted. Statistical heterogeneity will be explored through subgroup analyses and meta-regression, examining study design, SDoH measurement approaches and population characteristics.

As a systematic review and meta-analysis, ethics approval is not required. For institutional oversight, we provide the contact of Dr Sonia Anand (Associate Vice-President, Global Health, McMaster University; anands@mcmaster.ca). Results will be reported following PRISMA guidelines and disseminated through a peer-reviewed publication.

CRD420251115759.

Within the UK there are 33 deaths every day from prostate cancer, second only to lung cancer as the most common cause of cancer death in males in the UK. Of the 55 000 new cases each year, up to 50% of these patients will receive radiotherapy either alone or after prostatectomy. Although there have been significant improvements in the accuracy of radiotherapy delivery leading to better tumour targeting and a reduction in dose to normal tissues, significant permanent genito-urinary or gastrointestinal-related side effects are all too common. With nearly 80% of patients with prostate cancer surviving for 10 years or more, minimising life-limiting radiation damage to normal tissues is vitally important. However, at present, it is not possible to identify which patients will suffer a poorer outcome after radiotherapy. The aim of this study, improving radiotherapy in PROState cancer using EleCtronic population-based healthCAre data (PROSECCA), is to do this by using the existing information in a patient’s digital healthcare record. By linking primary, secondary and tertiary clinical data, including digital image information, with radiotherapy treatment plans and outcome data, the PROSECCA study will identify de novo predictive biomarkers of radiation response and provide clinicians with a tool to individualise a radiotherapy dose and plan to maximise cure and minimise toxicity.

The PROSECCA study is a large multidisciplinary project, the purpose of which is to analyse healthcare records from up to 15 000 patients with prostate cancer who underwent radiotherapy in the treatment of their cancer in Scotland between 2010 and 2022. Through the linkage of data obtained specifically for radiotherapy and data held within each patient’s unique electronic health record (EHR), the factors that indicate why some patients have a poor response to treatment, or an increased risk of side effects from radiation, will be identified. This will be made possible by the use of artificial intelligence and machine learning (AL/ML), which will help to identify at-risk patients earlier and allow adaptation of their treatment accordingly.

The study is being conducted in accordance with the ethical principles set out in the Declaration of Helsinki and Good Clinical Practice that respects and protects the rights, and maintains confidentiality, of all trial participants. The study protocol (V.1.0) was reviewed by the South Central Oxford A Research Ethics Committee (REC) on 13 December 2021 and received a favourable opinion subject to each National Health Service (NHS) organisation confirming permission for patients treated within their area. Approval for the use of unconsented healthcare record data for patients included in the study and treated at one of the five Scottish Cancer Centres required an application to the NHS Scotland Public Benefit and Privacy Panel for Health and Social Care (HSC-PBPP). Full approval from the HSC-PBPP panel was received on 1 July 2024, which covered the use of pseudoanonymised EHR data for all patients participating in the study. The study is publicly listed on the NHS Health Research Authority site, with IRAS ID 306245 and REC reference 21/SC/0402. Dissemination of the study findings will take place through field-leading cancer, radiation oncology and medical physics journals. All manuscripts will be approved by the main study team and authorship determined by mutual agreement.

NCT06714630.

The objective of this scoping review is to identify and describe factors that affect access to post-sepsis care. Considering the burden faced by sepsis survivors, it is important to understand the facilitators and barriers to accessing post-sepsis care to facilitate the design and implementation of patient-centred and equitable pathways to care.

This scoping review will include studies that consider individuals who have experienced sepsis and any factors that may affect access to care, including comorbidities, discharge setting and social determinants of health. A comprehensive search of MEDLINE, Embase, Emcare, HealthSTAR and Scopus will be conducted. The extracted data will be summarised and presented thematically.

Approval from a research ethics board is not required for this review as it is a synthesis of information from studies where the primary investigators have already received approval from their respective ethics boards. Once complete, the review will be submitted for publication in a peer-reviewed journal, and the findings will be shared to local and national forums.

This review has been uploaded and registered under Open Science Framework. https://doi.org/10.17605/OSF.IO/JMFW2

To evaluate the association between asthma-related emergency department (ED) visits and weather, air quality, monsoons, haze and cultural festivals in Singapore.

Retrospective cohort study.

A public healthcare cluster that covers 20% of the nation’s adult asthma population.

2617 adult patients accounting for 5337 asthma ED visits between 2016 and 2024.

Temperature, rainfall, wet bulb temperature (WBT), wind speed and Pollution Standards Index (PSI) were correlated with asthma ED counts at 0–7 day lags. Associations between ED visits and monsoons, transboundary haze and cultural festivals were evaluated using one-way analysis of variance. Weekly seasonal ARIMA models with exogenous regressors were fitted, incorporating PSI as a covariate and adjusting for demographic, clinical and socioeconomic factors.

Asthma ED visits were positively correlated with PSI (lag 0: r=0.142; 95% CI 0.107 to 0.178) and inversely correlated with rainfall (lag 3: r=–0.062; 95% CI –0.099 to –0.026) and WBT (lag 1: r=–0.067; 95% CI –0.104 to –0.031). Wind speed (lag 2: r=–0.049; 95% CI –0.086 to –0.013) and ambient temperature (lag 6: r=–0.045; 95% CI –0.081 to –0.008) showed weaker inverse associations. Mean PSI was higher during haze (82.67 vs 51.46, p

PSI–ED association peaked on the same day of exposure but was no longer significant after adjusting for demographic and clinical factors. Pollution-linked festivals, transboundary haze and the Northeast monsoon were associated with increased asthma ED visits

Process evaluation provides insight into how interventions are delivered across varying contexts and why interventions work in some contexts and not in others. This manuscript outlines the protocol for a process evaluation embedded in a hybrid type 1 effectiveness-implementation randomised clinical trial of incremental-start haemodialysis (HD) versus conventional HD delivered to patients starting chronic dialysis (the TwoPlus Study). The trial will simultaneously assess the effectiveness of incremental-start HD in real-world settings and the implementation strategies needed to successfully integrate this intervention into routine practice. This manuscript describes the rationale and methods used to capture how incremental-start HD is implemented across settings and the factors influencing its implementation success or failure within this trial.

We will use the Consolidated Framework for Implementation Research (CFIR) and the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) frameworks to inform process evaluation. Mixed methods include surveys conducted with treating providers (physicians) and dialysis personnel (nurses and dialysis administrators); semi-structured interviews with patient participants, caregivers of patient participants, treating providers (physicians and advanced practice practitioners), dialysis personnel (nurses, dieticians and social workers); and focus group meetings with study investigators and stakeholder partners. Data will be collected on the following implementation determinants: (a) organisational readiness to change, intervention acceptability and appropriateness; (b) inner setting characteristics underlying barriers and facilitators to the adoption of HD intervention at the enrollment centres; (c) external factors that mediate implementation; (d) adoption; (e) reach; (f) fidelity, to assess adherence to serial timed urine collection and HD treatment schedule; and (g) sustainability, to assess barriers and facilitators to maintaining intervention. Qualitative and quantitative data will be analysed iteratively and triangulated following a convergent parallel and pragmatic approach. Mixed methods analysis will use qualitative data to lend insight to quantitative findings. Process evaluation is important to understand factors influencing trial outcomes and identify potential contextual barriers and facilitators for the potential implementation of incremental-start HD into usual workflows in varied outpatient dialysis clinics and clinical practices. The process evaluation will help interpret and contextualise the trial clinical outcomes’ findings.

The study protocol was approved by the Wake Forest University School of Medicine Institutional Review Board (IRB). Findings from this study will be disseminated through peer-reviewed journals and scientific conferences.

NCT05828823.

Non-adherence to tuberculosis (TB) treatment remains a major challenge in high-burden regions. However, few studies have qualitatively examined the sociocultural and emotional barriers to adherence, particularly among Afghan refugees in Pakistan. This study explores the patient-related, sociocultural and treatment-related barriers to treatment adherence among patients with TB of Pakistani and Afghan origin living in Pakistan.

We conducted an exploratory qualitative study consisting of semistructured focus group discussions (FGDs) and in-depth interviews (IDIs) with purposively selected multisectoral stakeholders. The data were analysed thematically using a combination of inductive and deductive approaches.

We employed a qualitative study design in the TB DOTS (Directly Observed Treatment Short course) centres in the Haripur and Peshawar districts of Khyber Pakhtunkhwa province, Pakistan.

We conducted IDIs (n=29) and FGDs (n=11) with three categories of participants: TB healthcare providers, patients with TB and their carers.

We identified several contributors to lower treatment adherence. These included patient-related barriers (eg, lack of awareness about TB and its treatment), sociocultural barriers (eg, stigma, refugee status of Afghan patients, gender roles and reliance on traditional and spiritual healing) and treatment-related barriers (eg, demanding treatment regimen and TB-induced depression).

Several personal, sociocultural and treatment-related barriers contribute to lower treatment adherence in patients with TB. A significant contributing factor to treatment non-adherence in patients is the high prevalence of anxiety and depression related to TB and its treatment, for which there is no treatment or counselling available at the DOTS level in Pakistan, warranting the need for mental health interventions that could improve adherence and treatment outcomes for both TB and depression.

ISRCTN10761003.

In Bangladesh, evidence on the long-term trajectory of adolescents' sexual and reproductive health (SRH) remains limited, largely due to the lack of longitudinal data to assess the changes over time. To address this gap, the Advancing Sexual and Reproductive Health and Rights (AdSEARCH) project of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) set up an adolescent cohort study aimed at documenting changes in SRH knowledge, attitudes and practices, and identifying the factors affecting these changes. This article presents the baseline sociodemographic and SRH characteristics of this cohort as a pathway for future analyses.

This cohort study included 2713 adolescents from the Baliakandi Health and Demographic Surveillance System run by icddr,b. The cohort covered three age groups from girls and boys, giving a total of five cohorts: girls aged 12, 14 and 16 years; and boys aged 14 and 16 years. A total of seven rounds of data had been collected at 4-month intervals over 2-years follow-up period.

The majority of adolescents were attending school (90%), and school dropouts were higher among boys. Around 17% of the respondents were involved in income-generating activities, which were mostly boys. Among girls, the mean age of menarche was 12.2 years. Overall, 6% of adolescents had major depressive disorder, with prevalence increasing with age. Gender differences were evident regarding knowledge about conception and contraception. Egalitarian attitudes towards social norms and gender roles were found higher among girls (52%) compared to boys (11%). The majority of adolescents reported experiencing social/verbal bullying (43%), followed by physical violence (38%) and cyberbullying (4%).

This article presents the baseline findings only. A series of papers is in the pipeline for submission to different peer-reviewed journals. The findings from this study will be used to support data-driven policy formulation for future adolescent health programmes.

Incretin-based drugs, including glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs, are increasingly used in the management of type 2 diabetes mellitus and obesity. While these agents have shown cardiovascular benefits, their effects on both cardiovascular outcomes and cardiac structure and function remain uncertain—particularly in patients with and without a history of heart failure (HF).

We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index-Science (CPCI-S)), as well as clinical trial registries from their inception and onwards to identify relevant randomised trials. The literature search is scheduled for July 2025. Two review authors will independently extract data and assess risk of bias. We will include randomised controlled trials assessing the effects of cagrilintide/semaglutide, liraglutide, semaglutide and tirzepatide in patients with and without a history of HF. The primary outcome will be cardiovascular mortality. Secondary outcomes will include HF hospitalisation, myocardial infarction, stroke, heart rate, systolic blood pressure, N-terminal pro B-type natriuretic peptide, left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricular end-systolic volume. Data will be synthesised by aggregate data meta-analyses and trial sequential analysis. Risk of bias will be assessed with the Cochrane Risk of Bias tool, version 2, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE).

As this study is a systematic review based on secondary analysis of published data, ethical approval is not required. Findings will be published in international peer-reviewed scientific journals.

CRD420251003374.

In the UK, approximately 5.4 million adults live with asthma, of whom one in five have an uncontrolled form. Uncontrolled asthma reduces quality of life and increases healthcare use. Engaging with peers through online health communities (OHCs) can empower patients to self-manage their long-term condition. While OHCs have been in existence for several years and growing numbers of patients access them, the role of primary care in signposting patients to them has been minimal and ad hoc. We have co-developed with patients and healthcare professionals (HCPs) an intervention for adult patients with asthma, consisting of an appointment with a primary care HCP to introduce online peer support and sign patients up to an established asthma OHC, followed by OHC engagement. Feasibility work found the intervention acceptable to patients and HCPs. This protocol outlines our plan to test the intervention’s effectiveness and cost-effectiveness.

An individual randomised controlled trial will be carried out. Eligible participants will be recruited via an online survey sent to adult patients on the asthma register in 50–70 general practices in several UK locations. Participants will be invited to attend a one-off, face-to-face appointment with a primary care HCP, during which they will be individually randomised to the intervention or usual care. An asthma control test (primary outcome) and other measures of clinical effectiveness will be collected at baseline and every 3 months over a 12-month follow-up period. Descriptive and inferential statistics will be used to compare outcome measures between study arms. Cost-effectiveness assessment of the intervention compared with current standard of asthma management in primary care will be reported. A sample of patients and HCPs will be interviewed at study exit and the data analysed thematically.

The study was approved by a National Health Service Research Ethics Committee (reference: 25/NE/0006). Written consent will be obtained from all participants. Findings will be disseminated through various means, including sharing with general practices, conference presentations and peer-reviewed publications.

NCT06849245.

Over the past two decades, initiatives promoting research-policy engagement have increased broadly and in health. Numerous factors influencing the engagement of policymakers in research have been described primarily from the perspective of researchers. This scoping review aimed to identify the enablers and barriers to policymaker engagement across the research process from the perspective of policymakers.

Scoping review following the Joanna Briggs Institute Methods Manual for scoping reviews.

MEDLINE, Cochrane Library, Social Policy and Practice, Campbell Collaboration, Health Systems Evidence and World Bank e-Library, supplemented by grey literature from Google Scholar, WHO Global Index Medicus and VHL Regional Portal.

We included English language studies published after 2007 that involved policymakers at national or subnational levels who were actively engaged in research at any stage. We excluded studies which did not include policymakers, where engagement was passive, or perspectives were marginal or not clearly outlined.

After screening and full-text review, we extracted and coded data using MAXQDA Plus 24. We conducted thematic analysis, categorising findings as enablers or barriers into three levels: individual, organisational and contextual/system. Findings were iteratively reviewed and refined by the research team.

We screened 5384 titles and abstracts, reviewed 59 full-text documents and included 30 articles for analysis. Most studies were published after 2016 and were focused on policymaker engagement at the national level. Organisational factors were the most frequently reported influences on engagement of policymakers in research across different contexts. The most frequent enablers mentioned in the literature were (1) the institutionalisation of partnerships, initiatives and having formal agreements; (2) defining goals, roles, responsibilities and conflict resolution mechanisms; (3) researchers providing practical and expert advice to policymakers; (4) leveraging networks; and (5) having supportive institutions. The most frequent barriers were (1) the lack of regulations, infrastructure, funding and communication channels to support engagement; (2) the lack of skills of researchers to understand policymaking processes and work in collaboration with policymakers; and (3) the mismatch in priorities, values, perspectives and expectations.

Our study highlights the role of institutional support, widespread collaboration opportunities and the interconnected nature of these factors within the research-policy ecosystem.

Open Science Framework (https://osf.io/ynr78/).

SARS-CoV-2 infection provides protection against reinfection and severe COVID-19 disease; however, this protective effect may diminish over time. We assessed waning of natural immunity conferred by previous infection against severe disease and symptomatic reinfection in Brazil and Scotland.

We undertook a test-negative design study and nested case–control analysis to estimate waning of natural immunity against severe COVID-19 outcomes and symptomatic reinfection using national linked datasets. We used logistic regression to estimate ORs with 95% CIs. A stratified analysis assessed immunity during the Omicron dominant period in Brazil.

We included data from the adult populations of Brazil and Scotland from 1 June 2020 to 30 April 2022.

Severe COVID-19 was defined as hospitalisation or death. Reinfection was defined as reverse-transcriptase PCR or rapid antigen test confirmed at least 120 days after primary infection.

From Brazil, we included 30 881 873 tests and 1 301 665 severe COVID-19 outcomes, and from Scotland, we included 1 520 201 tests and 7988 severe COVID-19 outcomes. Against severe outcomes, sustained protection was observed for at least 12 months after primary SARS-CoV-2 infection with little evidence of waning: 12 months postprimary infection: Brazil OR 0.12 (95% CI 0.10 to 0.14), Scotland OR 0.03 (95% CI 0.02 to 0.04). For symptomatic reinfection, Brazilian data demonstrated evidence of waning in the 12 months following primary infection, although some residual protection remained beyond 12 months: 12 months postprimary infection: OR 0.42 (95% CI 0.40 to 0.43). The greatest reduction in risk of SARS-CoV-2 infection was in individuals with hybrid immunity (history of previous infection and vaccination), with sustained protection against severe outcomes at 12 months postprimary infection. During the Omicron dominant period in Brazil, odds of symptomatic reinfection were higher and increased more quickly over time when compared with the overall study period, although protection against severe outcomes was sustained at 12 months postprimary infection (whole study: OR 0.12 (95% CI 0.10 to 0.14); Omicron phase: OR 0.15 (95% CI 0.12 to 0.19)).

Cross-national analyses demonstrate sustained protection against severe COVID-19 disease for at least 12 months following natural SARS-CoV-2 infection, with vaccination further enhancing protection. Protection against symptomatic reinfection was lower with evidence of waning, but there remained a protective effect beyond 12 months from primary infection.