Type 2 diabetes mellitus has been associated with an increased risk of cognitive decline and dementia, with patients being 1.5–2 times more likely to develop these conditions. While both sodium-glucose co-transporter 2 (SGLT2) inhibitors and thiazolidinediones (TZDs) have shown potential neuroprotective effects in previous studies, their comparative effectiveness for preventing neurodegenerative outcomes has not been established. This study aimed to compare the risk of stroke, dementia and Alzheimer’s disease (AD) between patients treated with SGLT2 inhibitors and those treated with TZDs.

Multicentre, retrospective, observational, new-user, active-comparator cohort study.

Electronic health record-based databases from 11 secondary and tertiary institutions in South Korea from 1 January 2014 to 31 July 2025. The study period began in 2014, following the post-marketing surveillance initiation of SGLT2 inhibitors in Korea (November 2013), to ensure adequate drug availability and clinical adoption.

Patients aged 40 years or older who were newly prescribed either SGLT2 inhibitors or TZDs without prior exposure.

Propensity score matching (1:1) was performed using sex as the primary covariate due to data availability constraints in the Observational Medical Outcomes Partnership Common Data Model framework. The HRs with 95% CIs were measured via Cox regression analysis.

The study analysed 24 172 matched pairs for stroke outcomes (40 483 person-years in the SGLT2 inhibitor group and 39 363 person-years in the TZD group), 25 111 matched pairs for dementia (41 924 person-years in the SGLT2 inhibitor group and 40 726 person-years in the TZD group) and 25 237 matched pairs for AD (42 139 person-years in the SGLT2 inhibitor group and 40 895 person-years in the TZD group) across 11 participating hospitals. After a 1:1 propensity score matching, the SGLT2 inhibitors showed no significant difference in stroke risk (HR 1.18, 95% CI 0.62 to 2.23, p=0.62), while having significant reductions in dementia risk (HR 0.66, 95% CI 0.45 to 0.98, p=0.04) and AD risk (HR 0.54, 95% CI 0.35 to 0.83, p=0.005). Moreover, these protective effects for neurodegenerative outcomes were shown to be consistent across multiple hospital sites.

SGLT2 inhibitors are associated with a reduced risk of dementia and AD compared with TZDs in patients aged 40 years or older with type 2 diabetes and have neutral effects on stroke risk. These findings confirm the potential selective neuroprotective benefits of SGLT2 inhibitors for neurodegenerative outcomes, which may inform therapeutic decision-making for diabetic patients at risk of cognitive decline.

Fetal alcohol spectrum disorder (FASD) is a diagnostic term that describes the neurodevelopmental and physical effects resulting from prenatal exposure to alcohol. Individuals living with FASD can experience lifelong challenges, yet with a diagnosis and sufficient support for the individual and their whānau (families), people can live fulfilling lives. Currently, little is known of the prevalence and impact in Aotearoa, New Zealand (NZ). Our aim is to identify the prevalence and understand the needs of young people living with FASD and other neurodevelopmental disorders in Youth Justice (YJ) residences in Aotearoa, NZ. One study will investigate the prevalence of FASD in this setting. The outcomes of both studies may demonstrate barriers and enablers, as well as strengths and gaps in YJ services of Aotearoa, NZ. The outcomes of both studies may guide reinforcing of current best practices as well as highlight necessary and novel initiatives together providing best support for the children and adolescents and their whānau as well as staff across YJ residences.

Extensive consultation with Māori and Pacific Advisory groups, researchers and experts in FASD and justice settings, individuals living with FASD and YJ staff together informed the development of this study.

Children and adolescents (hereafter young people) aged 10 to 18 years and currently residing in YJ residences are eligible for participation and assessment for FASD through assenting and consenting to provide personal and social histories and completed physical and neuropsychological assessments. The comprehensive FASD histories, screening and assessment will be conducted by a neuropsychologist and paediatrician employing standardised assessment practices and instruments. The team will also collect information from health, education and care and protection records; from the young people themselves; and from their family and staff. The study will reference Whakakotahitanga, the newly released (2024) guidelines for screening and diagnosing FASD in Aotearoa, NZ while also acknowledging the differences imposed under constraints of funding research including, for example, time and money. An individualised report will be prepared for each young person and their whānau. Study data will be analysed with descriptive statistics as appropriate. Our findings will be considered by the Māori and Pasifika advisory groups for framing and culturally secure translation, disseminated with all participating young people, translated to YJ services and staff, government and community neurodiversity sectors. Outcomes will be made available through community hubs, conferences, reports and peer-reviewed journal publications.

The study has received ethical approval from the Southern Health and Disability Ethics Committee (2024 Full 20065). Locality ethical approval has been granted from Oranga Tamariki (Ministry of Children), and a privacy impact evaluation has been undertaken. The findings will be shared through peer-reviewed publication, local and national conferences and with key agencies including Oranga Tamariki.

The real-world evidence on the association between vitamin D supplementation and cognitive outcomes has been scant and controversial. We aimed to investigate the longitudinal association between vitamin D supplement use and subsequent cognitive functioning among US older adults.

Prospective cohort study.

A nationally representative ageing cohort in USA: the Health and Retirement Study (HRS).

Participants were drawn from the HRS wave 12 and included respondents who had complete data on dietary supplement use and cognitive assessment. A total of 5065 participants (mean age: 67.5±10.2 years, 61.6% female, 76.6% White ethnicity) were included, of whom 2004 (39.6%) participants were vitamin D supplement users.

Change in cognitive function scores over 6 years of follow-up (from HRS waves 12–15), estimated by linear mixed model adjusted for multiple covariates.

Compared with non-users, vitamin D users had an accelerated decline in global cognitive function (difference in the rate of change: –0.052 points/year; 95% CI –0.092 to –0.013, p=0.010) and in executive function score (difference: –0.021 points/year; 95% CI –0.037 to –0.005, p=0.010). Sensitivity analysis suggested that accelerated cognitive decline was only observed among supplement users with normal baseline serum 25(OH)D level (p=0.004), but not the group with insufficient/deficient levels (p=0.826).

Our findings do not support vitamin D supplementation as a means of preventing or slowing cognitive decline in older people with adequate vitamin D status. While healthcare providers should encourage adequate vitamin D intake from dietary sources and moderate sun exposure, caution should be taken when recommending such supplements to older adults without a clear indication for it.

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract distinguished by progressive bowel damage with a risk of structuring and penetrating complications. It is characterised by focal or segmental transmural inflammation that disrupts intestinal mucosal integrity and favours the development of abscesses and fistulas. Perianal fistula develops in 13%–39% of patients with CD. Their care is difficult but improves with medical and surgical treatment to preserve anal continence and avoid a maximum proctectomy. Combined treatment with seton placement and concomitant anti-TNF (infliximab, adalimumab) allows wound healing in 40%–70% of cases. The currently available treatments are not curative and fail to provide a long-term resolution. The injection of adipose stromal cells is currently being evaluated in clinical studies for repair-damaged tissues in various diseases (limb ischaemia, osteoarthritis, systemic sclerosis, etc). Immunoregulatory and anti-inflammatory properties of AdMSC (adipose-derived stroma/stem cells) are responsible for accelerating healing and represent an innovative approach for treating perianal fistulas associated with CD.

This phase I/IIa study is designed to assess the treatment of complex perianal fistulas linked with CD after failure of conventional treatment by injection of AdMSC (CellReady) into the fistula. Two doses of associated AdMSC will be tested for a dose escalation (5x10⁷ and 10x10⁷ cells) and injected into the wall of the fistula. Those eligible for inclusion include patients with controlled luminal CD characterised by a Harvey-Bradshaw score below or equal to eight and diagnosed on clinical, endoscopic, histological and/or radiological criteria, a colonoscopy dating back less than 1 year without ulcer in the rectum and presence of complex chronic perianal fistula with a maximum of two internal ports and three external ports. All patients must have social security insurance or equivalent social protection. The aim of this study is to determine the optimal dose corresponding to maximum efficacy 6 months after injection of cells with a treatment-related adverse event rate of 20%.

The EU CT number 2024-511821-75-00 was approved by the following Ethics Committee: CPP (committee for the protection of persons in French: comité de protection des personnes) Ouest 1 – Tours #2024UEMED-18 and ANSM (French Agency for the Safety of Health and Medicinal Products in French : Agence nationale de sécurité du médicament et des produits de santé) #2024-511821-75-00 (Sponsor number RC31/13/7030, protocol V2.1). The results will be disseminated through conventional scientific channels.

NCT06636032.

The results will be disseminated through conventional scientific channels.

To identify parent/caregiver perspectives prior to taking part in a transition care intervention involving group education sessions and peer support for parents/caregivers of adolescents with T1D.

Pre-intervention, semi-structured interviews were conducted with parents/caregivers of adolescents (14–16 years) with T1D followed in a tertiary care paediatric diabetes clinic and participating in a pilot, randomised controlled trial: The Group Education Trial to Improve Transition for Parents/Caregivers of Adolescents with T1D (ClinicalTrials.gov ID: NCT05445284). We conducted a reflexive thematic analysis to identify key aspects of the intervention that may help support parents/caregivers of adolescents with T1D during their transition to adult care.

Of the 17 parents/caregivers randomized to the intervention group, 13 completed pre-intervention interviews.

Four themes were generated from the parents/caregivers, including (1) Creating a Community of Learners (i.e., importance of fostering a bidirectional and supportive environment for parents/caregivers), (2) Psychological Perspectives of Parenting (i.e., acknowledgement of shifting parental/caregiver roles during adolescents’ transition), (3) Diabetes Management During Adolescence (i.e., identification of relevant diabetes education topics to be covered), and (4) Ideal Format and Delivery of the Program (i.e., practical recommendations for the logistics of the intervention).

The findings provide practical and pragmatic suggestions to refine the parent/caregiver-based transition of care intervention for a future, full-scale trial, including addressing parental/caregiver needs as they learn how to best support their adolescent with T1D during transition to adulthood. Future transition programmes for adolescents with T1D may also benefit by incorporating aspects of the current transition readiness program for parents/caregivers of adolescents with T1D.

Many researchers conduct a process evaluation alongside an effectiveness trial of a public health intervention to better understand mechanisms behind observed effects. Yet, there is no standardised, scientifically accepted guideline for reporting such process evaluations, which impedes interpretation and comparison of study results. The aim of this project was to develop a consensus-based and expert-based guideline for reporting process evaluations of public health interventions conducted alongside an effectiveness trial.

We conducted an e-Delphi study with a large panel of international experts.

Based on purposive sampling, we invited 137 international experts that had been involved in the design of process evaluations, researchers who published high-profile process evaluations or frameworks, editors of journals that publish process evaluations, and authors of other reporting guidelines.

Based on a literature search, a first draft of the reporting guideline included 32 items, which was proposed to panel members during the first round. Of the invited 137 invited international experts, 73 (53%) participated in at least one round of the e-Delphi study. Participants rated the inclusion and comprehensibility of the proposed items on a 5-point Likert scale and provided comments and suggestions for relevance and definitions of the items. Adjustments to the items and descriptions were proposed to the e-Delphi panel until consensus of ≥67% for each individual item was reached. In total, 64 (88% of 73) completed round 2, and 55 (76% of 73) completed round 3. This resulted in 19 items that are included in the consensus-based process evaluation reporting guideline for public health intervention studies (CONPHES) guideline. The items cover a detailed description of the intervention that is evaluated, the implementation strategies applied, and underlying causal pathways, and the role of the delivery and support team. The guideline also requires describing the evaluation framework and how evaluation outcomes were assessed. Lastly, the guideline includes items on providing a detailed description of applied analyses (both quantitative and qualitative) and measures for assuring quality. The guideline is accompanied by an Explanation and Elaboration document, with a more detailed explanation of each item.

We expect that the CONPHES reporting guideline for process evaluations of public health interventions can improve the reporting of process evaluations of interventions aimed at promoting public health. This can potentially facilitate more effective translation of public health research into practice and contribute to improving both individual and population health outcomes.

Non-occupational post-exposure prophylaxis (nPEP) and pre-exposure prophylaxis (PrEP) are effective HIV prevention methods, but their use is low in Sub-Saharan Africa (SSA). Mobile applications (apps) could increase uptake and adherence to these interventions, yet research on their use in communities is limited. Furthermore, there is limited information on the design and development of these apps, impacting their implementation. This scoping review aims to identify, analyse and evaluate mobile apps designed to improve nPEP uptake, adherence and linkage to PrEP services focusing on key features, barriers and facilitators. It also seeks to address gaps in studies assessing the feasibility, usability and acceptability of these apps, with the goal of informing future research, healthcare policies and public health strategies to reduce the HIV burden in Sub-Saharan Africa.

This review will follow the Arksey and O'Malley framework and search databases such as PubMed, Scopus and Web of Science for relevant studies. Two independent reviewers will screen and assess full-text studies. Primarily, the review will include studies on digital interventions for nPEP and PrEP, excluding opinion papers, narrative reviews and sub-studies. Grey literature from sources like Google Scholar will also be considered. Data will be captured using a charting form, and results will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews framework. Completion is expected in December 2025.

No ethical approval is required as publicly available materials will be used. Results will be shared through peer-reviewed journals, conferences and with policymakers to inform HIV prevention strategies.

Neutropenic fever (NF) has a crude mortality rate of 3–18%. International guidelines recommend that all patients with NF receive ultrabroad-spectrum antibiotics (UBSAs) within 1 hour of emergency department (ED) registration. However, over 70% patients presenting to hospital with suspected NF (sNF) cannot access absolute neutrophil count (ANC) result within 1 hour, do not have NF and do not require UBSAs. In ED and hospitalised patients with sNF, we hypothesise that the ASTERIC protocol effectively and safely reduces the use of UBSAs compared with standard care alone.

This pragmatic, parallel, multicentre, type 1, hybrid effectiveness-implementation, stepped-wedge, before-and-after, cluster randomised controlled trial aims to evaluate whether antibiotic prescribing can be safely reduced through implementing a multifaceted antibiotic stewardship intervention (ASTERIC) in adult patients with sNF presenting to EDs. The sNF was defined as a fever with a single oral temperature of ≥38.3°C (101°F) within 24 hours before ED registration or a temperature of ≥38.0°C (100.4°F) sustained over a 1-hour period, following last chemotherapy or targeted therapy within 6 weeks for any solid tumour, or in any period following therapies against leucaemia, lymphoma, myelodysplastic syndrome, aplastic anaemia, multiple myeloma or recipient of HSCT. The study will involve eight hospitals in Hong Kong with variable baseline practice. We will include 704 adult patients (352 patients in pre-implementation and post-implementation periods, respectively) with sNF (tympanic temperature ≥38.3°C) and 48 staff participants (6 staff participants in each hospital). Healthcare professionals will receive a multifaceted stewardship intervention consisting of risk assessment tools, fast-track ANCs, a decision tool for patient management and antibiotic use, supported by an educational package and staff interaction programmes (ASTERIC protocol). Patients’ blood ANC, and cancer therapy and chronic illness therapy scores will be measured. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) and Proctor conceptual frameworks will be followed for evaluation of implementation. The main outcome measures are the mean total dose of UBSAs prescribed in 7 days and serious adverse events at 30 days. Data analysis will incorporate intention-to-treat, per-protocol and as-treated analyses for service outcomes (effectiveness, safety, quality of life assessments and cost-effectiveness) and mixed methods for implementation outcomes, informed by the Theoretical Domains Framework. We expect that the study results will inform health policy with improvement in hospital services in treating stable sNF, evidenced by improved safe antibiotic stewardship, early antibiotic de-escalation and reduced costs and length of stay.

The institutional review boards of all study sites approved this study. This study will establish the ASTERIC protocol safely improves antibiotic stewardship and clinical management in adult patients with sNF. We will disseminate the findings through peer-reviewed publications, conference presentations and educational activities. All patients with sNF will be influenced by the new protocol which is agreed at hospital level. Randomisation is at hospital level, not patient level. Patient consent is sought for follow-up and data access, not for treatment. Staff consent is sought for interviewing.

NCT06794320.

Increasing reports of life-threatening complications in young children exposed to skin-lightening products present a significant public health concern, yet this issue remains under-researched.

To determine the prevalence, maternal perceptions and predictors of early childhood exposure to skin-lightening products among mothers in Southwestern Nigeria.

A cross-sectional, questionnaire-based study.

Three randomly selected government-owned primary healthcare facilities in Ile-Ife, Nigeria.

Three hundred and sixty-nine mothers aged ≥18 years, each with at least one child under 5, recruited by simple random sampling. Data were collected between May and July 2024 using pretested, interviewer–administer semistructured questionnaires. Mothers with acutely ill children were excluded.

Primary outcome was the use of skin lightening products on children while secondary outcomes included maternal use, perceptions and sociodemographic/familial predictors.

Participants’ ages ranged from 18 to 54 years (mean: 30.92±6.11 years). Overall, 19.5% (n=72) mothers practised early childhood skin lightening, with 80.6% of exposed children

This study highlights a high prevalence of early childhood exposure to lightening products in a semiurban Nigerian community, with maternal use emerging as a key associated factor. Although awareness of potential health risks was common, aesthetic preferences for lighter skin tones appeared to outweigh safety concerns. These findings highlight the need for culturally sensitive interventions and further research to inform strategies that promote safer childhood skin-care practices.

Type 1 diabetes (T1D) demands self-management skills, knowledge and confidence to prevent medical complications. Adolescents living with T1D have distinct developmental challenges resulting in a worsening in glycaemic stability, irregular care and an increased risk for complications all while transitioning to adult healthcare. Age-specific online platforms could facilitate transition by fostering self-management education and support. The Support online self-guided training platform has been shown to increase the confidence of adults with T1D in managing their glycaemia. We aim to test the effectiveness of Support-t (ie, adapted for youth), compared with usual care, in improving haemoglobin A1c (HbA1c) and to understand the context of its implementation.

We will conduct a multisite, assessor-blinded, randomised controlled, parallel group, two-arm, superiority trial, evaluating effectiveness and implementation of Support-t versus usual care in 200 adolescents (14–16 years old) living with T1D. The active arm will have an 18-month access to Support-t, and their healthcare team will be trained on the platform’s content. The control arm will receive usual care. The primary outcome is HbA1c at 18 months. Secondary outcomes include self-efficacy for diabetes self-management, transition readiness, diabetes-specific quality of life, diabetes distress, continuous glucose monitoring metrics, number of severe hypoglycaemic events, diabetic ketoacidosis, T1D-related emergency department visits and hospitalisations as well as engagement and satisfaction. A subgroup of participants in the active arm and of healthcare providers will be interviewed assessing barriers, facilitators, engagement and fidelity of the intervention. Primary analysis will be by intention-to-treat. The difference in mean HbA1c at 18 months (with a 95% CI) will be calculated between both arms. A cost-effectiveness analysis is also planned.

December 8, 2024 version of the protocol was approved by the McGill University Health Centre Research Ethics Board (MP-37-2024-9734). Results will be disseminated through peer-reviewed publications and patient-partners’ network.

ClinicalTrials.gov (NCT05910840).

Male infertility can be primary or secondary, depending on whether pregnancy has been achieved before or not, but thyroid gland involvement is rarely investigated in the laboratory work-up. This study aimed to assess thyroid hormone abnormalities among primary and secondary infertile men.

This is a cross-sectional study involving male partners of infertile couples presenting at the fertility clinic with an established diagnosis of infertility after review by the clinician. Males with proven fertility served as controls.

The study was conducted at the Human Reproduction and Research Programme unit and the Chemical Pathology Laboratory of the University of Benin Teaching Hospital, Benin City, Edo State, Nigeria.

This study involved 200 participants who consisted of 50 controls (fertile men) and 150 infertile men (80 primary infertile men and 70 secondary infertile men). The participants were reviewed by a clinician, and a semen analysis was done to ascertain their fertility status.

The results show that sperm indices, such as sperm count, total motility, progressive motility, viable sperm cells, normal forms and volume were significantly lower (p

Thyroid abnormalities were more predominant among secondary infertile men than primary infertile men in this study.

The co-occurrence of multiple long-term conditions, that is, multimorbidity, is increasing globally and is associated with lower quality of life and increased risk of death. The risk and prevalence of multimorbidity are higher among women compared with men, but currently, evidence focusing on women’s multiple long-term conditions during the perinatal period is limited. Existing evidence needs to be examined to determine the extent to which maternal multimorbidity or women’s multiple health needs related to pregnancy have been addressed, especially for women living in low-income and middle-income countries (LMICs) where this burden of disease is the highest. The objective of this scoping review is to map existing evidence in LMICs on (a) Study designs and data sources, (b) Context-relevant definitions and descriptions, (c) Associated risk and protective factors, (d) Relevant maternal and infant health outcomes and (e) Treatments and interventions used to manage multiple long-term conditions before, during and after pregnancy.

This scoping review will be conducted using Joanna Briggs Institute methodology and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement extension for scoping reviews. This review will include observational, experimental or quasi-experimental studies, as well as systematic or umbrella reviews, on multimorbidity in women of reproductive age (15–49 years) in prepregnancy, pregnancy or up to 6 weeks after childbirth in LMICs. The studies will focus on definitions, risk and protective factors and management strategies for multiple long-term conditions before, during and after pregnancy. Studies of morbidity in women with a single index condition or conditions that are not related to pregnancy or childbirth will be excluded. A search strategy will be developed using thesaurus (including MeSH) and free-text terms for ‘maternal morbidity’ or ‘multiple long-term conditions’ and associated keywords such as multimorbidity, co-morbidity and unmet health needs related to pregnancy and/or childbirth for women living in LMICs. Electronic (EBSCOhost (CINAHL Ultimate, STM Source, Medline Ultimate), Cochrane Library, Web of Science or Scopus and Google Scholar) and grey literature databases will be searched from database inception. Reference lists and bibliographies of key topic articles will also be searched, and any additional papers that meet the inclusion criteria will be obtained. There will be no limitations on dates or languages. Records will be independently screened, selected and extracted by two researchers. Data will be presented in tables and narrative summaries.

Ethics approval is not required as this scoping review will summarise previously published data. Findings from the review will be disseminated through various platforms, including peer-reviewed journals, conferences and community meetings.

Open Science Framework (https://doi.org/10.17605/OSF.IO/FYCR8).

The open, prospective Community-Based chronic Care Lesotho (ComBaCaL) cohort is the first study to comprehensively investigate socioeconomic indicators, common chronic diseases and their risk factors in a remote rural setting in Lesotho. It serves as a platform for implementing nested trials using the Trials within Cohorts (TwiCs) design to assess community-based chronic care interventions. In this study, we present the cohort’s sociodemographic and chronic disease risk factor profile, including self-reported HIV prevalence and hypertension and diabetes care cascades.

Since February 2023, community health worker (CHWs) supported by a clinical decision support and data collection application have enrolled inhabitants from 103 randomly selected rural villages in Butha-Buthe and Mokhotlong districts in Northeast Lesotho. As of 31 May 2024, the cohort includes 5008 households with 14 735 participants (55% female, median age 19 years). The cohort’s socioeconomic status is low with an International Wealth Index of 26, a monthly household income of US$42.4 and low levels of formal education. Among the 7917 adult participants, 42.5% are overweight or obese, with higher rates among women, and 33.1% smoke tobacco, with higher rates among men. Self-reported HIV prevalence is 15.1% with a 98.4% treatment rate. Hypertension prevalence is 17% with a 56% control rate and diabetes prevalence is 4% with a 39% control rate.

The cohort’s low socioeconomic status is linked to multiple health risks including insufficient access to clean energy, essential healthcare services, adequate sanitary facilities and secure food supply. Besides the expected high HIV prevalence, we found significant hypertension, diabetes and cardiovascular risk factor prevalences. While treatment and control rates for diabetes and hypertension are higher than in similar settings, they remain below global targets.

Ongoing cluster-randomised TwiCs, which will be completed in 2025, are assessing the effectiveness of community-based, CHW-led care interventions for diabetes and hypertension. CHWs will continue to closely monitor the cohort and integrate additional measurements such as HIV testing. This will provide further insights into the dynamics and interactions of chronic diseases and inform the development of future nested trials on innovative community-based prevention and care interventions.

NCT05596773.