This study aimed to investigate the association between smoking behaviours during early pregnancy and the risk and severity of gestational diabetes mellitus (GDM), with a particular focus on smoking status, smoking intensity and secondhand smoke exposure.

Secondary analysis of prospectively collected cohort data.

Multi-centre study conducted in South Korea (Korean Pregnancy Outcome Study) between March 2013 and January 2017.

From 4537 pregnant women initially enrolled, 3457 singleton pregnancies were included after excluding cases with transfer, loss to follow-up, twin pregnancies, miscarriages and pre-existing diabetes mellitus. All participants were women of Korean ethnicity.

Primary outcome was GDM and its subtypes (A1GDM: diet-controlled; A2GDM: insulin-requiring). Secondary outcomes were associations with active smoking (before pregnancy and during early pregnancy), smoking intensity dose–response relationships (pack-years) and secondhand smoke exposure among never-smokers.

Among 3457 participants, 231 women (6.7%) were diagnosed with GDM (198 A1GDM, 33 A2GDM). Active smoking before pregnancy (adjusted OR (aOR) 3.98, 95% CI 1.58 to 9.30) and during early pregnancy (aOR 9.90, 95% CI 2.97 to 29.45) were significantly associated with A2GDM, while no significant association was observed with A1GDM. A clear dose-response relationship was observed, with smoking intensity >4 pack-years markedly increasing A2GDM risk (aOR 20.68, 95% CI 6.75 to 59.39). Detailed pack-year analysis showed 4–6 pack-years (aOR 20.57, 95% CI 5.80 to 65.46) and >6 pack-years (aOR 25.98, 95% CI 3.21 to 146.45). Among never-smokers, secondhand smoke exposure showed a borderline association with overall GDM risk (aOR 1.33, 95% CI 0.98 to 1.81).

Maternal active smoking before and during early pregnancy, as well as higher smoking intensity, was associated with an increased risk of pharmacologically treated GDM (A2GDM). Although secondhand smoke exposure did not reach statistical significance, the trend suggested a potential association with GDM risk among never-smokers. These findings provide important evidence for public health strategies for prenatal care, as smoking cessation and environmental smoke avoidance during prenatal and early antenatal care in women reduce the risk of gestational diabetes.

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.

To investigate associations between shift work patterns and sleep disturbance, and to assess if the association is modified by demographic factors, socioeconomic factors, anthropometric and lifestyle factors, health conditions or sleep traits.

Analysis of cross-sectional data obtained from the UK Biobank baseline assessment.

UK Biobank, a large-scale prospective cohort study which recruited half a million participants aged 40–69 years between 2006 and 2010 from across the UK.

A total of 285 175 employed or self-employed participants at baseline (2006–2010), including 148 296 (52.0%) females and 136 879 (48.0%) males. The sample comprised 94.0% White, 0.7% Mixed race, 0.36% East Asian, 2.0% South Asian, 1.8% Black and 0.89% from other ethnic backgrounds.

Sleep disturbance was defined as the presence of both insomnia and excessive sleepiness symptoms.

A total of 42 181 (14.8%) participants had sleep disturbance defined based on insomnia and excessive sleepiness. 236 200 (82.8%) were non-shift workers, while 48 975 (17.2%) were shift workers, which included 24 062 (49.1%) working day shifts only, 17 940 (36.6%) working night shifts sometimes or usually, and 6973 (14.2%) working night shifts always. Compared with non-shift workers, all shift workers had higher multivariable-adjusted odds of sleep disturbance: (non-night shifts: OR in model 3 (OR) 1.21 (95% CI 1.16 to 1.27); sometimes/usually night shifts: OR 1.37 (95% CI 1.30 to 1.44) and always night shifts: OR 1.50 (95% CI 1.38 to 1.63)). The association between shift work pattern and sleep disturbance was modified by age (p_interactioninteraction=0.0005) and smoking status (p_interaction=0.04).

Shift work is associated with a higher odds of sleep disturbance compared with non-shift work in all participants, with greatest odds observed among those always working night shifts. The association was stronger among individuals who were younger than 55 years old, from an ethnic minority background and never smokers. Future large-scale longitudinal studies are needed to further investigate these associations.

This study assessed whether a previously developed Monte Carlo simulation model can be reused for evaluating various strategies to minimise time-to-treatment in southwest Netherlands for endovascular thrombectomy (EVT) in patients who had an ischaemic stroke.

Reuse of a previously developed simulation model to simulate various strategies in another region, using prospectively collected data from stroke centres and retrospective data from emergency medical services.

Data from 509 patients who had an ischaemic stroke (≥18 years) treated with EVT (2014–2018) were used.

Input for the simulation model reuse included distributions of observed time delays along the acute stroke pathway. Validation of the baseline models was based on face validity and statistical measures (patient data vs model output) using the Assessment of the Validation Status of Health Economic decision models tool. We simulated strategies for a subregion: interhospital patient transfer by helicopter, transport of the neurointerventionalist to the primary stroke centre (‘drive-the-doctor’), interhospital patient transfer to a thrombectomy-capable stroke centre (TSC) outside the region and prehospital triage using the Rapid Arterial Occlusion Evaluation (RACE) scale.

Onset-to-groin time was the outcome.

Reuse of the original simulation model was obtained by minimal effort, implying limited adaptation. Compared with the baseline model, interhospital patient transfer by helicopter or to a TSC outside the region and prehospital routing using the RACE scale reduced mean onset-to-groin time by 16, 13 and 39 min, respectively (95% CrI for all: equal to the point estimate). ‘Drive the doctor’ reduced mean onset-to-groin time by 27 (car), 49 (ambulance) or 58 min (helicopter), each with a 95% CrI equal to the point estimate.

The original simulation model can be applied to different regions in the Netherlands. Strategies tested within the subregion resulted in promising results of ‘drive the doctor’ and prehospital patient routing using the RACE scale.

The WHO recommends task-sharing with community health workers (CHWs) to help overcome the limited access to hearing healthcare and hearing aids in low-income and middle-income settings (LMIs). This systematic review examined the feasibility, efficacy and effectiveness of CHW-facilitated hearing aid provision.

Systematic review guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines.

PubMed, Scopus and Web of Science were searched through 4 June 2025.

Studies in which CHWs facilitated hearing aid provision in any context.

Data on study characteristics, CHW training and roles, hearing-aid outcomes and implementation factors were extracted. Study quality was determined using the National Institute of Health quality assessment tool, and level of evidence was determined using the Centre for Evidence-Based Medicine. A narrative synthesis was conducted.

Six studies published between 2013 and 2025 were included. Two were conducted in high-income countries but implemented in LMI communities. Four studies were conducted in LMI countries. All provided CHW training, though content and duration varied; only one used WHO-endorsed materials. Sustained device use was high as reported at follow-ups, though only one included 12-month outcomes. All studies included validated outcome measures, including the International Outcome Inventory for Hearing Aids, Hearing Handicap Inventory for the Elderly–Screening version, Abbreviated Profile of Hearing Aid Benefit and Self-Efficacy for Situational Communication Management Questionnaire. Implementation facilitators included use of local CHWs, delivery in participants’ home languages, comprehensive CHW training and employing mHealth tools. Barriers included CHW scope constraints and unfamiliarity with outcome subscales in rural contexts. Only two studies used formal feasibility frameworks.

CHW-facilitated hearing aid provision is feasible and effective. However, variation in training and implementation highlights the need for standardised training materials, supervision models and culturally adapted outcome measures. Further research should examine long-term outcomes, cost-effectiveness and scalability using formal implementation frameworks.

To examine chronic kidney disease (CKD) prevalence, incidence, prognosis, kidney function decline and associated risk factors among people with diabetes and/or hypertension.

Cross-sectional multicentre study.

14 primary care centres across Jakarta.

Adults (≥18 years) with diabetes and/or hypertension were included. Exclusion criteria were receiving kidney replacement therapy, language barrier, cognitive impairments, refusal to consent and pregnancy. Participants were grouped into three categories: hypertension only, diabetes only and both.

None.

Primary outcomes included CKD prevalence, incidence, number-needed-to-screen, KDIGO-based prognosis and annual kidney function decline. Secondary outcomes were risk factors for CKD, uncontrolled blood glucose, blood pressure and albuminuria.

A total of 1263 participants were enrolled: 51% had hypertension, 17.6% diabetes and 31.4% both. Mean age: 57.1±10.2 years, 72.2% female and 76% obese. Renin angiotensin aldosterone system inhibitors were prescribed in 32.3%, and only 1.2% used insulin despite a median glycated haemoglobin of 7.5% (IQR: 6.5–9.1). CKD prevalence was 14.8%, with an incidence rate of 9.1 per 100 person-years; number-needed-to-screen was 7. Based on KDIGO criteria, 48.9% were at moderate-to-very high risk of adverse outcomes. Baseline estimated glomerular filtration rate was 80.9 (SE=10.1), declining by 4.7 (SE=9.9) mL/min/1.73 m² annually. CKD incidence was higher with albuminuria (OR 3.6, p=0.007) in the combined group; older age (OR 4.5, p

CKD burden is high among people with diabetes and hypertension. Nearly half were at elevated risk despite preserved kidney function, highlighting the need for targeted early screening.

To examine the association between friendly community environments and depressive symptoms among older adults in China and to investigate the potential mediating roles of happiness and confidence in this association.

A nationally representative longitudinal study employing the parallel mediation model to estimate the direct association. Bootstrapping procedures were employed to test the hypothesised mediating effects.

The China Family Panel Studies (CFPS) database, a nationally representative survey.

The analytical sample comprised 3182 individuals aged 60 years or older from the CFPS 2016, 2018 and 2020 waves.

Depressive symptoms were measured using an eight-item version of the Center for Epidemiologic Studies Depression Scale. Higher scores indicated more depressive symptoms. Friendly community environment, happiness and confidence were assessed using corresponding survey items.

The analysis revealed a significant direct negative association was observed between friendly community environments and depressive symptoms (β=–0.062, 95% CI –0.092 to –0.035, p

Friendly community environments are negatively associated with depressive symptoms among older adults in China, primarily by enhancing happiness and confidence in life. To promote healthy ageing, it is crucial to create comfortable, clean and convenient community environments tailored to the older adult population.

Sepsis and antibiotic resistance constitute a deadly synergy, causing the loss of millions of lives across the world, with their economic and developmental consequences posing a threat to global prosperity. Their impact is disproportionately felt in resource-limited settings and among vulnerable populations, especially children. A key challenge is prompt diagnosis and timely commencement of appropriate antibiotic therapies. These challenges are compounded in low-income and middle-income countries by a lack of comprehensive epidemiological data, with Nigeria being one such country for which it is lacking. Kaduna is the third largest state in Nigeria, with over 10 million inhabitants, of whom more than half are children under 14 years old. While bacterial sepsis and antimicrobial resistance (AMR) are recognised as a growing problem in the state, there are huge gaps in the current understanding of their aetiology. This project employs a cross-sectional design to investigate the clinical and haematological markers of paediatric sepsis, alongside determining the bacterial cause and prevalence of AMR at four high-turnover hospitals in Kaduna State, Nigeria. Further, whole-genome sequencing of isolated bacterial pathogens will be performed to determine the genetic features of resistance. This project represents the largest surveillance study of paediatric sepsis in Kaduna to date. Additionally, we aim to use the clinical, haematological, microbiological and genomic data to derive predictive models for sepsis causes, treatment strategies and patient outcomes.

This is a hospital-based, cross-sectional study that will recruit up to 461 children with bacterial sepsis who were admitted at the two teaching and two general hospitals in Kaduna State, Nigeria. Children presenting with features of fever, subnormal temperature and body weakness would be recruited into the study and have their blood samples collected. The blood samples will be used for culture, complete blood count, HIV and malaria testing. Accordingly, we will capture clinical presentation, haematological characteristics, causative pathogen from blood culture and patient outcomes. Nutritional status, known congenital immunosuppressive diseases, HIV infection and malaria infection will also be determined and documented. The bacterial isolates will be phenotypically characterised for AMR and genotypically following whole genome sequencing. Known and potential confounders to the outcomes of bacterial sepsis would be assessed in all participants, and adjustment for confounding would be performed using logistic regression and/or stratification±Mantel-Haenszel estimator where applicable.

Ethical approvals were granted by the University of Birmingham (ERN_2115-Jun2024), the Ahmadu Bello University Teaching Hospital (ABUTHZ/HREC/H45/2023), Barau Dikko Teaching Hospital, Kaduna (NHREC/30/11/21A) and the Kaduna State Ministry of Health (MOH/AD M/744/VOL.1/1110018). The study will be conducted using the international guidelines for good clinical practice and based on the principles of the Declaration of Helsinki. The results will be disseminated via oral and poster presentations in scientific conferences and published in peer-reviewed journal articles.

Cystic fibrosis (CF) is a genetic condition of impaired membrane electrolyte transport and is characterised by defects in the production and function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Ground-breaking CFTR modulator therapy has resulted in a notable shift in the clinical presentation and progressive nature of CF, across both pulmonary and extrapulmonary systems. Access to CFTR modulator therapies in people with CF is occurring in a staged, descending age process, with clinical trials focusing primarily on safety and efficacy. There is a lack of robust, real-world longitudinal data on CFTR modulator therapy in infants and young children where extrapulmonary outcomes such as growth, micronutrient status and pancreatic function are the key focus.

Pancreatic, nutritional and clinical outcomes in children 0–5 years with CF during the first 2 years of CFTR modulator therapy (PaNC) is a prospective cohort study involving all eight tertiary paediatric CF centres in Australia. Infants and children 4 months to 5 years of age who are eligible for elexacaftor/tezacaftor/ivacaftor (ETI) or ivacaftor (IVA) meet the inclusion criteria for PaNC, with a total eligible cohort of 303 children at the commencement of recruitment. The primary outcomes are change in weight-for-length/body mass index z score and change in serum micronutrient status, at 6–12 monthly intervals, during the first 2 years of treatment with ETI or IVA. Secondary outcomes include change in exocrine pancreatic function, measured by faecal elastase-1, change in the use and dose of pancreatic enzyme replacement therapy, nutritional and gastrointestinal therapies and change in sweat chloride levels. Linear mixed modelling will be used to analyse primary and secondary endpoints. This protocol is reported in accordance with ‘The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement’ reporting guidelines.

Overarching governance and ethics approval has been granted by Monash Health Human Research Ethics Committee, in addition to all eight sites receiving site-specific authorisation approvals prior to the commencement of recruitment. Opportunities for CF consumers to be involved in targeted dissemination plans will be initiated via CF Australia at the completion of the study period. Additionally, a summary of non-identifiable results will be provided to CF consumers and CF healthcare providers via scientific and lay conferences and via peer-reviewed journals.

ACTRN12624001185550; Pre-results.

Acute intracerebral haemorrhage (ICH) is devastating with a 1 month mortality rate of ~40%. Cerebral oedema can complicate acute ICH and is associated with poor outcome. In patients with large ICH, the accompanying swelling increases mass effect and causes brain herniation. Mannitol, an osmotic diuretic, is used to treat cerebral oedema after traumatic brain injury, but its safety and efficacy in ICH is unclear. We aim to assess the feasibility of a phase II randomised, controlled trial of mannitol in patients with ICH with, or at risk of, cerebral oedema to inform a definitive trial.

The mannitol for cerebral oedema after acute intracerebral haemorrhage trial (MACE-ICH) aims to include 45 ICH participants from 10 UK sites with estimated largest diameter of haematoma volume >2 cm, presenting within 72 hours of onset with, or at risk of, cerebral oedema (limited Glasgow Coma Scale (GCS)8) with or without mass effect. Participants will be randomised (1:1:1) to 1 g/kg 10% single-dose intravenous mannitol, 1 g/kg 10% mannitol followed by a second dose at 24 hours, or standard care alone. Outcome assessors will be masked to treatment allocation. Feasibility outcomes include proportion of patients approached being randomised, participants receiving allocated treatment, recruitment rate, treatment adherence and follow-up. Secondary outcomes include serum electrolytes and osmolality at days 1–2; change in ICH and oedema volume at day 5; number of participants who developed urinary tract infection, GCS and National Institutes of Health Stroke Scale at day 5±2; length of hospital stay, discharge destination and death up to day 28; death and death or dependency by day 180 and disability (Barthel Index), quality of life (EuroQol, 5-D) and cognition (telephone mini-mental state examination) at day 180.

MACE-ICH received ethics approval from the East Midlands-Leicester Central research ethics committee (22/EM/0242). The trial is funded by a National Institute for Health and Care Research RfPB grant (203080). The results will be published in an academic journal and disseminated through academic conferences and patient support groups. Reporting will be in line with Consolidated Standards of Reporting Trials recommendations.

ISRCTN15383301; EUDRACT 2022-000283-22.

For patients with perihilar cholangiocarcinoma (pCCA), surgical resection remains the sole treatment modality that can potentially result in cure. Unfortunately, the majority of patients present with unresectable tumours or are excluded from surgical treatment due to complications like cholangitis affecting their performance status. In the Netherlands, recommended first-line treatment for patients with unresectable pCCA is palliative chemotherapy with gemcitabine and cisplatin. This regimen yields an estimated median overall survival (OS) of 11.7–15.2 months, highlighting the urgent need for novel treatment options. The STRONG I trial, a phase I study in patients with unresectable pCCA, was completed in 2020. Its aim was to assess the feasibility and toxicity profile of adding stereotactic body radiation therapy (SBRT) to chemotherapy. SBRT, delivered in 15 fractions of 4.0 Gray (Gy), was considered to be feasible and safe, with no dose-limiting toxicity being observed. The 1-year local tumour control rate was 80% and the 1-year OS rate 100%, with maintenance of quality of life (QoL). These results encouraged us to initiate the STRONG II trial, aiming to investigate the efficacy of adding SBRT to chemotherapy in a larger patient cohort.

STRONG II is a single-arm, multicentre phase II study. Patients with non-metastatic unresectable pCCA (T1-4, N0-2) are eligible. A total of 30 patients will be enrolled in six academic centres in the Netherlands and two in Belgium. SBRT will be delivered in 15 fractions of 4.0–4.5 Gy. The primary endpoint is local tumour control, defined by Response Evaluation Criteria in Solid Tumours (RECIST) V.1.1. Secondary endpoints include toxicity, biliary stent-related events, progression-free survival, OS and QoL using the EuroQoL five-dimensional, five-level (EQ-5D-5L) questionnaire, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) and the EORTC Biliary Module (QLQ-BIL21). In addition, we will explore the predictive value of the peripheral immunological status (immune-related proteins and serum functional immunological status assay) and its dynamics in determining survival outcomes. For this explorative translational study, two blood samples will be collected, one before the start of chemotherapy and another after completing chemotherapy.

Approval of the study was obtained on 5 June 2024 by the Medical Ethics Review Committee of Erasmus Medical Center Rotterdam, the Netherlands (ID: NL86210.078.24). The anticipated time frame for patient enrolment is July 2024 to December 2027. The main study findings will be published in peer-reviewed medical journals, and presented at national and international conferences.

NCT06493734 (ClinicalTrials.gov).

Raltegravir is a potent HIV-integrase strand transfer inhibitor (INSTI). Despite its strong activity against HIV-1 strains resistant to other antiretroviral drug classes, it is usually used in combination with other antiretroviral drugs due to the empirical requirement for anti-HIV drug combinations to ensure effective anti-retroviral therapy (ART). As an early-arriving INSTI, raltegravir is clinically familiar for its safety, tolerability and treatment effectiveness. High-dose calcium carbonate formulated as an antacid (as opposed to a supplement formulation) taken orally together with raltegravir is known to reduce systemic raltegravir exposure due to chelation and reduced absorption. This study aims to assess the effect of daily calcium carbonate antacid as TUMS Ultra Strength (US) administration in lower doses, as currently used for oral calcium supplementation, on the steady-state pharmacokinetics (PKs) of once-daily oral raltegravir.

This is an open-label, three-treatment series in three periods in a single group, fixed-sequence PK study in 12 healthy adult volunteers with HIV on ART. Subjects will take 1200 mg of raltegravir single QD oral dose alone for 7 days (period one), then raltegravir 1200 mg with calcium carbonate 500 mg from day 8 to day 14 (period two) and raltegravir 1200 mg with calcium carbonate 1000 mg from day 15 to day 22 (period three). We will conduct serial PK sampling from observed dosing on days 7, 14 and 21, with 24-hour PK sampling scheduled for days 8, 15 and 22. Follow-up will continue until day 51.

This study will adhere to the ICH GCP Guidelines and the Declaration of Helsinki. Ethics approval was obtained from the Ottawa Health Science Network Research Ethics Board under study ID 20190750–01 hour. Informed consent will be obtained from all participants prior to enrolment. This protocol will be published in a peer-reviewed journal prior to the study’s completion and closure. Results generated from this activity will also be reported in a peer-reviewed journal.

NCT04258475.