In May 2023, the US Food and Drug Administration (FDA) initially approved an AS01_E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (adjuvanted RSVPreF3) for adults aged ≥60 years. The approval was expanded in June 2024 to include adults 50–59 years of age at increased risk for RSV-associated lower respiratory tract disease. In this paper, we describe the protocol of a postmarketing safety study evaluating the association between adjuvanted RSVPreF3 and new-onset Guillain-Barré syndrome (GBS), acute disseminated encephalomyelitis (ADEM) and atrial fibrillation (AF) among adults ≥50 years of age in the USA and provide our rationale for key methodological decisions.

The potential associations between adjuvanted RSVPreF3 and GBS, ADEM and AF will be evaluated using secondary healthcare data and the self-controlled risk interval (SCRI) design. Data from five research partners in the USA spanning August 2023 through June 2030 will be used for the conduct of yearly monitoring queries and, sample size permitting, SCRI analyses. Claims-based definitions for new-onset outcomes (first diagnosis in 365 days) are: ≥1 inpatient diagnosis for GBS and ADEM; ≥1 inpatient or ≥2 ambulatory/emergency diagnoses for AF. The primary risk and control windows are 1–42 and 43–84 days, respectively, for GBS and ADEM; and 1–8 and 9–16 days for AF. SCRI analyses for GBS and ADEM will include chart-confirmed cases. SCRI analyses for AF will adjust for the positive predictive value obtained from validation against charts. Conditional Poisson regression will be used to calculate incidence rate ratios.

This study was approved by the Institutional Review Boards (IRB) of Harvard Pilgrim Health Care Institute; WIRB-Copernicus Group, Inc and its affiliates (collectively, ‘WCG’); WCG IRB, Inc; and Sterling IRB, with Federal Wide Assurance (FWA) numbers FWA00000100, FWA00033319 and FWA00025632, respectively, for all participating research partners. Study results will be shared with the US FDA and publicly disseminated through national or international clinical or scientific conferences and peer-reviewed publications.

This protocol has been registered in the Heads of Medicines Agencies–European Medicines Agency Real World Data Catalogues (EUPAS1000000486).

In 2023, 21% of deaths occurred in residential aged care facilities (RACFs), a setting expected to play an increasing role in palliative and end-of-life care (PEoLC). General practitioners (GPs) oversee and deliver PEoLC in residential and nursing homes, yet little is known about their practice. We conducted a systematic review of the published evidence concerning how GPs provide this care: what they do and the quality, challenges and facilitators of that care.

Systematic review and narrative synthesis using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Medline, Embase, CINAHL, PsycINFO, Web of Science, Scopus and NHS Evidence and grey literature via Google Scholar were searched through 9 October 2024.

We included studies presenting new empirical data from qualitative, quantitative or mixed methods, were published in the English language and conducted in the UK, the European Union, Australia, New Zealand and Canada. We excluded studies with no new empirical data, discussion papers, conference abstracts, opinion pieces, study participants under 18 years old and in care settings other than RACF.

One independent reviewer used standardised methods to search and screen study titles for inclusion. This reviewer assessed all abstracts of the included papers, and a second independent reviewer screened 60% of the abstracts to validate inclusion. Risk of bias was assessed using Gough’s Weight of Evidence assessment. Thematic analysis was used to describe the contents of the included papers; a narrative synthesis approach was taken to report the findings at a more conceptual level.

The search identified 5936 titles: 35 papers were eligible and included in the synthesis. This is a nascent evidence base, lacking robust research designs and characterised by small sample sizes; the results describe the factors observed to be important in the delivery of care. Care provision is extremely variable; no models of optimal care have been put forward or tested. Challenges to care provision occur at every level of the care system. At macro level, service-level agreements and policies vary: at meso level, team-working, communication technology solutions and equipment availability vary: at micro level, GPs’ interests in providing PEoLC vary as does their training. No study addresses residents’ and relatives’ experiences and expectations of GPs' involvement in PEoLC in RACFs.

The limited evidence base highlights that GP care at end of life for RACF residents varies greatly, with enablers and challenges at all levels in the existing care systems. Little research has examined GP PEoLC for RACF residents in its own right; insight is derived from studies that report on this issue as an adjunct to the main focus. With national policies focused on moving more PEoLC into community settings, these knowledge deficits require urgent attention.

With the global population ageing rapidly, older adults face increased risks of physical and cognitive decline. Despite the well-documented benefits of physical activity (PA), many older adults fail to meet PA guidelines. Mobile health (mHealth) apps offer promising tools to promote PA, but user engagement remains a challenge. In response, the MIA app was co-created with older adults using the Behavior Change Wheel framework to enhance usability, relevance and sustained engagement. A feasibility study showed promising results in usability and user satisfaction, supporting further evaluation. The goal of this study is to evaluate the effectiveness of MIA on PA promotion in older adults.

A randomised controlled trial conducted in Belgium at a university college will assess the effectiveness of the MIA app in promoting PA in older adults. Participants will be randomly assigned in a 1:1 ratio to either the intervention group (MIA app use) or the control group (no use of MIA) for 8 weeks. The primary outcome is moderate-to-vigorous PA, measured via Garmin wearable devices. Secondary outcomes include self-reported measures (PA, well-being, user satisfaction), clinical assessments (physical and cognitive functioning) and time series assessments (daily steps). A total of 75 participants will be recruited to ensure sufficient power, accounting for dropout. Eligible participants must be ≥65 years, medically stable, have no significant cognitive or physical limitations, understand and speak Dutch and have access to a smartphone and/or computer. Exclusion criteria include an active lifestyle, participation in other exercise programmes or clinical trials, or any condition deemed by a healthcare professional to compromise safety or study validity.

The study was approved by the UHasselt Medical Ethics Committee (B1152025000012) and complies with Belgian legislation on human research. Written informed consent will be obtained from all participants prior to enrolment. Data will be securely stored for up to 25 years. Results will be disseminated via peer-reviewed publications and conference presentations.

NCT06983574.

To explore existing evidence for the provision of support for return to work (RTW) in long COVID (LC) patients and the barriers and facilitators to taking up this support.

A rapid review reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study was preregistered in PROSPERO (ID: CRD42023478126).

Searches were completed in June 2024 across major databases including MEDLINE, Embase, PsycINFO, evidence-based medicine reviews, Web of Science and Google Scholar.

Included studies focused on people with LC (PwLC) symptoms lasting over 12 weeks and addressed either: (1) non-workplace- or workplace-based support for RTW and/or (2) barriers and facilitators to RTW in this population.

A quality assessment was conducted using the JBI Systematic Reviews critical appraisal tool. The data were summarised in tabular format and a narrative synthesis.

Twenty-five studies were included. While many studies demonstrated rigorous methodologies and low risk of bias levels, some had high and medium risk levels. Non-workplace-based support was mostly measured quantitatively and included interdisciplinary healthcare programmes, clinical interventions and rehabilitation programmes focusing on pacing and breathing strategies. Compensation and insurance schemes were important funders of these interventions.

Workplace-based support was mostly measured qualitatively. Barriers to the provision of support at organisational level included lack of understanding of LC symptoms, insufficient workplace guidance and educational gaps among managers. Individual barriers included threat of income loss, remote working and disconnection from the workplace. Facilitators for support included recognition and validation of LC and its symptoms, and eligibility for disability benefits associated with work.

RTW is an important outcome of health-related absence and should be systematically recorded in studies of PwLC. The heterogeneity and unpredictability of LC symptoms create challenges for supporting working age populations. Further research is crucial to better understand the specific RTW needs for PwLC and address potential barriers and facilitators to workplace-based support, particularly through interventions, organisational practices and employ-led policies that enable sustained RTW. Consistent guidelines on LC’s definition and disability status may facilitate the provision of support and the development of interventions.

CRD42023478126.

This study aims to develop a methodology to retrieve, harmonise and evaluate the completeness of national body mass index (BMI) data from linked electronic health record (EHR) sources to build a longitudinal research-ready data asset (RRDA).

A longitudinal study of BMI records spanning 23 years (1 January 2000 to 31 December 2022) from four data sources.

The national BMI RRDA is created within the Secure Anonymised Information Linkage (Databank), encompassing the entire population of Wales, UK.

We built a methodology that provides a reproducible framework for extracting and harmonising BMI data from four major linked EHRs across two age groups: children and young people (CYP; 2–18 years old) and adults (19 years and older). The methodology is adaptable across different trusted research environments. We evaluated the completeness and retention of records over 1-, 5- and 23-year periods by calculating the proportion of missing data relative to each year’s population.

We retrieved 53.4 million records for 3.2 million individuals across Wales from 1st January 2000 to 31 December 2022. Among these, 3% of CYP and 34% of adults had repeat BMI measurements recorded over periods ranging from 5 to 23 years. Throughout the entire population of Wales during this period, 49% of CYP and 26% of adults had at least one BMI reading recorded, resulting in a missingness rate of 51% for CYP and 74% for adults. Preserving BMI information by retaining the most recently recorded BMI over 1-, 5- and 23-year intervals from 2022 showed coverage rates of 10%, 33% and 68%, respectively, for CYP, and 25%, 51% and 73%, respectively, for adults.

Our findings highlight substantial variations in BMI data availability and retention across CYP and adults, as well as time periods within EHR in Wales. Wider adoption of this approach can enhance standardised approaches in using accessible measures like BMI to assess disease risk in population-based studies, strengthening public health initiatives and research efforts.

Sweden, as many other high-income countries, has adopted guidelines to offer induction of labour at 41+0 gestational weeks to decrease the risk for perinatal death. As more than 20% of the pregnant population reach this gestational age, and along with other contributing factors, induction rates have increased up to 30% in many countries. Both women and care providers have raised the question if outpatient induction could be a convenient, safe and economic alternative, reducing the burden on inpatient care in maternity hospitals. Before introducing outpatient induction into clinical routine, studies need to assure safety for the child and woman as well as efficacy of the method.

A register-based randomised controlled multicentre non-inferiority trial to study if outpatient induction in low-risk inductions is (1) as safe for the child (perinatal composite of mortality and morbidity) and (2) as effective (proportion of vaginal deliveries) as inpatient induction at the hospital. Secondary outcomes are further health outcomes, experiences of pregnant women, partners and care providers, health economics and future pregnancy outcome. Participating women with a singleton pregnancy and unripe cervix between 37+0 and 41+6 gestational weeks planned for low-risk induction will undergo induction of labour with either a balloon catheter or oral misoprostol according to clinical practice at the study site and the woman’s informed choice. Randomisation will allocate women to either outpatient (home or patient hotel) or inpatient induction (standard care). Women undergoing outpatient induction can remain at home for up to 2 days, with an assessment after 24 hours including cardiotocography. Once active labour ensues, all women will receive standard care in the hospital.

The assessment of non-inferiority will involve a two-sided 95% CI and 80% power, requiring randomisation of 8891 women to ensure a probability of at least 0.80 that the upper limit of a two-sided 95.7% CI for a difference in the primary safety outcome is below the non-inferiority margin of 1.5%. 31 of the 45 delivery units in Sweden are currently recruiting. Data will be collected from the electronic case report form and Swedish healthcare registers. Questionnaire and qualitative interview-based studies will be performed to explore experiences of pregnant women, partners and care providers. Additionally, a health economic evaluation will be performed.

The Swedish Ethical Review Authority approved the study (3 June 2020; 2020-02675 with amendments 2021-03045, 2022-00865-02, 2023-01252-02, 2024-00560-02, 2024-2024-04597-02). The Swedish Medical Products Agency approved the study for the medication arm (25 August 2020, EudraCT number: 2020-000233-41; 5.1-2020-60240 with amendments 5.1-2022-73500, 5.1-2023-630). Due to changed regulation, in 2023, the study medication arm was transferred and approved by the European Medicines Agency (23 October 2023, EU CT Number: 2023-507164-39-00; CTIS 5.1.2-2023-099775 with amendments 5.1.2-2024-081916, 5.1.2-2025-036291). The Swedish Medical Products Agency approved the study for the medical device arm (6 April 2021, CIV-ID: CIV-20-09-034712; 5.1-2021-14812 with amendments 5.1-2022-14252, 5.1-2023-596, 5.1-2024-8886, 5.1-2024-55554). The medical device arm was transferred to Regulation (EU) 2017/745 (23 December 2024, 5.1-2025-24242 and amendment 5.1-2025-6050). The study will involve more than 80% of all delivery units in Sweden, which will allow for a smooth implementation of any new routine after the study’s conclusion. Results will be published in relevant scientific journals, presented at national and international conferences, and communicated to participants and relevant institutions through the Outpatient Induction study homepage (www.optionstudien.se), the webinars of the Swedish Network for National Clinical Studies in Obstetrics and Gynecology (www.snaks.se) as well as social and public media.

EudraCT No: 2020-000233-41, after transfer to the European Medicines Agency EU CT Number: 2023-507164-39-00; CIV-ID 20-09-034712.