Although lung cancer remains the leading cause of cancer deaths in the US, recent advances in early detection and treatment have led to improvements in survival. However, there is a considerable risk of recurrence or second primary lung cancer (SPLC) following curative-intent treatment in patients with early-stage non-small cell lung cancer (NSCLC). Professional societies recommend routine surveillance with CT to optimise the detection of potential recurrence and SPLC at a localised stage. However, no definitive evidence demonstrates the effect of imaging surveillance on survival in patients with NSCLC. To close these research gaps, the Advancing Precision Lung Cancer Surveillance and Outcomes in Diverse Populations (PLuS2) study will leverage real-world electronic health records (EHRs) data to evaluate surveillance outcomes among patients with and without guideline-adherent surveillance. The overarching goal of the PLuS2 study is to assess the long-term effectiveness of surveillance strategies in real-world settings.

PLuS2 is an observational study designed to assemble a cohort of patients with incident pathologically confirmed stage I/II/IIIA NSCLC who have completed curative-intent therapy. Patients undergoing imaging surveillance will be followed from 2012 to 2026 by linking EHRs with tumour registry data in the OneFlorida+ Clinical Research Consortium. Data will be consolidated into a unified repository to achieve three primary aims: (1) Examine the utilisation and determinants of CT imaging surveillance by race/ethnicity and socioeconomic status, (2) Compare clinical endpoints, including recurrence, SPLCs and survival of patients who undergo semiannual versus annual CT imaging and (3) Use the observational data in conjunction with validated microsimulation models to simulate imaging surveillance outcomes within the US population. To our knowledge, this study represents the first attempt to integrate real-world data and microsimulation models to assess the long-term impact and effectiveness of imaging surveillance strategies.

This study involves human participants and was approved by the University of Florida Institutional Review Board (IRB), University of Florida IRB 01, under approval number IRB202300782. The results will be disseminated through publications and presentations at national and international conferences. Safety considerations encompass ensuring the confidentiality of patient information. All disseminated data will be de-identified and summarised.

Multiple sclerosis (MS) is a chronic neurological condition that affects approximately 150 000 people in the UK and presents a significant healthcare burden, including the high costs of disease-modifying treatments (DMTs). DMTs have substantially reduced the risk of relapse and moderately reduced disability progression. Patients exhibit a wide range of responses to available DMTs. The Predicting Optimal INdividualised Treatment response in MS (POINT-MS) cohort was established to predict the individual treatment response by integrating comprehensive clinical phenotyping with imaging, serum and genetic biomarkers of disease activity and progression. Here, we present the baseline characteristics of the cohort and provide an overview of the study design, laying the groundwork for future analyses.

POINT-MS is a prospective, observational research cohort and biobank of 781 adult participants with a diagnosis of MS who consented to study enrolment on initiation of a DMT at the Queen Square MS Centre (National Hospital of Neurology and Neurosurgery, University College London Hospital NHS Trust, London) between 01/07/2019 and 31/07/2024. All patients were invited for clinical assessments, including the expanded disability status scale (EDSS) score, brief international cognitive assessment for MS and various patient-reported outcome measures (PROMs). They additionally underwent MRI at 3T, optical coherence tomography and blood tests (for genotyping and serum biomarkers quantification), at baseline (i.e., within 3 months from commencing a DMT), and between 6–12 (re-baseline), 18–24, 30–36, 42–48 and 54–60 months after DMT initiation.

748 participants provided baseline data. They were mostly female (68%) and White (75%) participants, with relapsing–remitting MS (94.3%), and with an average age of 40.8 (±10.9) years and a mean disease duration of 7.9 (±7.4) years since symptom onset. Despite low disability (median EDSS 2.0), cognitive impairment was observed in 40% of participants. Most patients (98.4%) had at least one comorbidity. At study entry, 59.2% were treatment naïve, and 83.2% initiated a high-efficacy DMT. Most patients (76.4%) were in either full- or part-time employment. PROMs indicated heterogeneous impairments in physical and mental health, with a greater psychological than physical impact and with low levels of fatigue. When baseline MRI scans were compared with previous scans (available in 668 (89%) patients; mean time since last scan 9±8 months), 26% and 8.5% of patients had at least one new brain or spinal cord lesion at study entry, respectively. Patients showed a median volume of brain lesions of 6.14 cm³, with significant variability among patients (CI 1.1 to 34.1). When brain tissue volumes z-scores were obtained using healthy subjects (N=113, (mean age 42.3 (± 11.8) years, 61.9% female)) from a local MRI database, patients showed a slight reduction in the volumes of the whole grey matter (–0.16 (–0.22 to –0.09)), driven by the deep grey matter (–0.47 (–0.55 to –0.40)), and of the whole white matter (–0.18 (–0.28 to –0.09)), but normal cortical grey matter volumes (0.10 (0.05 to 0.15)). The mean upper cervical spinal cord cross-sectional area (CSA), as measured from volumetric brain scans, was 62.3 (SD 7.5) mm². When CSA z-scores were obtained from the same healthy subjects used for brain measures, patients showed a slight reduction in CSA (–0.15 (–0.24 to –0.10)).

Modelling with both standard statistics and machine learning approaches is currently planned to predict individualised treatment response by integrating all the demographic, socioeconomic, clinical data with imaging, genetic and serum biomarkers. The long-term output of this research is a stratification tool that will guide the selection of DMTs in clinical practice on the basis of the individual prognostic profile. We will complete long-term follow-up data in 4 years (January 2029). The biobank and MRI repository will be used for collaborative research on the mechanisms of disability in MS.

To further elucidate the effects of rare systemic autoimmune rheumatic diseases (SARD) and their treatment on antibody development after vaccination against SARS-CoV-2, we compared patients with and without immunosuppressive therapy to healthy controls in an observational cohort study.

We enrolled 52 patients with SARD and 72 healthy subjects in a prospective, observational study at the Medical University of Vienna and measured the humoral response 6 months after two mRNA vaccinations and 2–6 weeks after a third dose.

Patients with vasculitis showed significantly (p=0.02) lower antibody titres 6 months after vaccination (median 247 BAU/mL, IQR [185–437]), as compared with healthy controls (median 514 BAU/mL, [185–437], IQR 323; 928, vasculitis patients: 247, IQR [185; 437], p

Patients with SARD displayed lower antibody development after booster vaccination, even if antibody levels after two immunisations were comparable to healthy controls. Our data may be limited due to sample size, but it provides pointers for a more individualised, antibody-titre-oriented approach and earlier booster vaccination in patients with SARD.

Preventing loss of autonomy has become a public health issue due to the increase in healthcare costs associated with ageing. It has become even more pressing with the arrival of the baby-boomer generation. This has given rise to several initiatives. This is the background to the VIVADOM project. The project provides a complete kit for older adults aged 60 years and over living at home. First, the kit includes a technological package (telecare, light path and digital tablet). Then, these older adults benefit from personalised human support provided by postal workers trained in gerontology. The aim of this study will be to carry out a health economic assessment (HEA) of the VIVADOM project as part of the prevention of frailty and/or dependency (by comparing beneficiaries of the complete kit with non-beneficiaries). The comparator will be the fact of not benefiting from the complete kit. In addition, the efficiency of the project in preventing falls and cognitive problems will be studied. We will calculate three incremental cost-effectiveness ratios (ICER) for these three issues.

The economic model used will be the Markov model. Transition probabilities, average costs and average quality-adjusted life year (QALY) will be calculated for the two groups being compared. The ICER will be obtained by dividing the difference in average costs by the difference in average QALYs. Finally, ICERs will be compared with willingness-to-pay (WTP) to assess the efficiency of the system. Thus, the VIVADOM project will be efficient when these ICERs are lower than the WTP. Univariate and probabilistic sensitivity analysis will be carried out to ensure the robustness of the analysis results.

The HEA of the VIVADOM project has been approved by the research unit of the University of Limoges in France. The results will be published in a peer-reviewed journal and presented at relevant national and international conferences.

Current guideline-recommended antibiotic treatment durations for ventilator-associated pneumonia (VAP) are largely standardised, with limited consideration of individual patient characteristics, pathogens or clinical context. This one-size-fits-all approach risks both overtreatment—promoting antimicrobial resistance and adverse drug events—as well as undertreatment, increasing the likelihood of pneumonia recurrence and sepsis-related complications. There is a critical need for VAP-specific biomarkers to enable individualised treatment strategies. The Ventilator-associated pneumonia Biomarker Evaluation (VIBE) study aims to identify a dynamic alveolar biomarker signature associated with treatment response, with the goal of informing personalised antibiotic duration in future clinical trials.

VIBE is a prospective, observational, case-cohort study of 125 adult patients with VAP in Michigan Medicine University Hospital intensive care units. Study subjects will undergo non-bronchoscopic bronchoalveolar lavage on the day of VAP diagnosis (Day 1) and then on Days 3 and 5. Alveolar biomarkers (quantitative respiratory culture bioburden, alveolar neutrophil percentage and pathogen genomic load assessed via BioFire FilmArray polymerase chain reaction) will be assessed. An expert panel of intensivists, blinded to biomarker data, will adjudicate each patient’s Day 10 outcome as VAP clinical cure (control) or treatment failure (case). Absolute biomarker levels and mean-fold changes in biomarker levels will be compared between groups. Data will be used to derive a composite temporal alveolar biomarker signature predictive of VAP treatment failure.

Ethical approval was obtained from the University of Michigan Institutional Review Board (IRB #HUM00251780). Informed consent will be obtained from all study participants or their legally authorised representatives. Findings will be disseminated through peer-reviewed publications, conferences and feedback into clinical guidelines committees.

The WHO has declared climate change the defining public health challenge of the 21st century. Incorporating climate and environmental outcomes in randomised trials is essential for enhancing healthcare treatments’ sustainability and safeguarding global health. To implement such outcomes, it is necessary to establish a framework for unbiased and transparent planning and reporting. We aim to develop extensions to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT 2025) and Consolidated Standards of Reporting Trials (CONSORT 2025) statements by introducing guidelines for reporting climate and environmental outcomes.

This is a protocol for SPIRIT and CONSORT extensions on reporting climate and environmental outcomes in randomised trials termed SPIRIT-Implementing Climate and Environmental (ICE) and CONSORT-ICE. The development of the extensions will consist of five phases: phase 1—project launch, phase 2—review of the literature, phase 3—Delphi survey, phase 4—consensus meeting and phase 5—dissemination and implementation. The phases are expected to overlap. The SPIRIT-ICE and CONSORT-ICE extensions will be developed in parallel. The extensions will guide researchers on how and what to report when assessing climate and environmental outcomes.

The protocol was submitted to the Danish Research Ethics Committees, Denmark in June 2025. Ethics approval is expected in September 2025. The SPIRIT and CONSORT extensions will be published in international peer-reviewed journals.

The Episodic Disability Questionnaire (EDQ) was developed to measure the presence, severity and episodic nature of disability experienced among persons with chronic conditions. Our aim was to assess the sensibility, utility and implementation considerations of the EDQ among older adults with complex health needs.

Cross-sectional measurement study involving quantitative and qualitative methods of data collection.

We recruited community-dwelling older adults (65 years of age or older) living with complex health needs receiving care from a primary healthcare team in Toronto, Canada.

We administered the EDQ, sensibility questionnaire (assessing face and content validity, and ease of usage, with each item scored from 0 to 7 with greater scores indicating greater sensibility) and demographic questionnaire, followed by a semi-structured interview in the home or clinical setting. Using an interview guide, we asked participants about their perspectives on utility, format and implementation of the EDQ in clinical practice. We considered the EDQ sensible if the median score on the sensibility questionnaire was ≥5/7 for ≥80% of items and if none of the items had a median score of ≤3/7. We conducted a team-based directed content analysis of the interview transcripts.

The median age of the 11 participants in this study was 83 years of age. All participants reported living with two or more chronic health conditions, with osteoarthritis (n=5) and diabetes (n=4) most frequently reported. The EDQ met the criterion for sensibility as measured by the sensibility questionnaire. Interview data from participants (n=10) indicated that the EDQ represents the health-related challenges among this sample of older adults with complex health needs, captures the episodic nature of disability and was easy to use. Utility of the EDQ included providing clinicians with a holistic understanding of health challenges older adults face, aiding in intervention planning and measuring changes in disability over time. Six of the participants also expressed uncertainty as to how the EDQ specifically could be used by clinicians in their care. Considerations for implementation included mode of administration (paper or electronic) and the importance of communicating EDQ scores with older adults based on individual preferences.

The EDQ possesses sensibility and utility for use among this sample of older adults living with complex health needs in home or clinical care settings.

To evaluate the effects of diabetes mellitus (DM) and body mass index (BMI) on long-term all-cause mortality in chronic total occlusion (CTO) patients.

Retrospective, nationwide cohort study.

Swedish Coronary Angiography and Angioplasty Registry, between June 2015 and December 2021.

24 284 patients with angiographically confirmed CTO. Prior coronary artery bypass graft surgery excluded. Subgroups were defined by DM status and BMI categories (underweight, healthy weight, overweight, obesity).

Long-term all-cause mortality, assessed by Kaplan-Meier analysis and multivariable Cox proportional hazards regression.

DM was present in 30.3% of patients and conferred a 31% higher risk of mortality (HR: 1.31, 95% CI: 1.20 to 1.42; p2, lowest risk (nadir) at 32 kg/m² and modest rise above 35 kg/m².

In this nationwide CTO cohort, DM independently predicted higher long-term mortality, accompanied by more severe comorbidities and greater CTO complexity, and insulin therapy further elevated hazard. Overweight and obese patients had better survival, while underweight individuals had the poorest prognosis. These findings underscore the importance of individualised risk assessment and management strategies in CTO patients, particularly those with DM or low BMI.

In non-intubated patients, symptomatic treatment of hypoxaemic respiratory failure is still debated, with different options: (1) standard oxygen therapy (SOT), (2) high-flow nasal cannula oxygen therapy (HFNC) and (3) non-invasive ventilation (NIV). The objective of this study is to compare the effects of HFNC and NIV on lung volumes assessed by CT scan to allow a better understanding of their effectiveness.

The HONIVAH study (High-flow Oxygen therapy and Non-Invasive ventilation on lung Volumes and on upper Airway in Hypoxemic critically ill patients) is an investigator-initiated, prospective, single-centre, physiological, randomised, parallel-group, unblinded trial with an electronic system-based randomisation. Patients with hypoxaemic respiratory failure, defined as the need for SOT flow ≥3 L/min to maintain a pulsed oxygen saturation ≥95%, and a CT scan prescribed by the physician in charge of the patient, will be randomly assigned to the HFNC group or the NIV group. Two inspiratory thoracic CT scans will be performed, one with SOT as part of the routine patient management and a second thoracic CT scan with HFNC or NIV, depending on the allocation group. The primary outcome is the comparison of the relative variation in ‘poorly aerated’ and ‘non-aerated’ lung volumes before and after the intervention between the HFNC group and NIV group, assessed by thoracic CT scan. Secondary outcomes included the variation in tracheal cross-sectional upper airway area, lung volumes, gas exchange and patient comfort.

The study project has been approved by the appropriate ethics committee (Comité de Protection des Personnes Sud-Ouest et Outre-mer 1, France, 2022-A02458-35). Informed consent is required. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

ClinicalTrials.gov identifier: NCT05643911.

The Cardiometabolic function in Offspring, Mother and Placenta after Assisted Reproductive Technology (COMPART) study is a prospective cohort study aiming to explore health outcomes in mothers and children following assisted reproductive technology (ART), with a particular focus on frozen embryo transfer (FET) versus fresh embryo transfer (fresh-ET). The increasing prevalence of ART and FET emphasises the need to assess potential health risks associated with the procedures, both in pregnancy, such as pre-eclampsia and large for gestational age offspring, and in the children, such as obesity and cardiometabolic dysfunction.

The cohort will include 600 pregnant women, their potential partner and their offspring in a 1:1:1 ratio of pregnancies achieved after ART with FET, ART with fresh-ET and women who conceived naturally. The study will involve extensive data collection from electronic medical records; parental questionnaires; biochemical, genetic and epigenetic analyses in blood, urine and placental tissue; and medical imaging (fetal ultrasound and PEA POD scan) and clinical examinations. Outcomes are grouped into six work packages (WPs) related to fetal growth (WP1), pregnancy (WP2), placenta (WP3), offspring (WP4), genetics (WP5) and epigenetics (WP6).

The COMPART study aims to provide valuable insights into the impact of ART and FET on maternal and offspring health and the underlying mechanisms responsible. The study seeks to advance reproductive medicine, shape clinical practice and guidelines and ultimately ensure maternal-fetal health following ART. The study has been approved by the Danish Ethics Committee (H-23071266; February 2024).

NCT06334003

Multimorbidity contributes significantly to poor population health outcomes while straining healthcare systems. Although some multimorbid patients experience an accelerated health decline (a decline in well-being or functional status that cannot be attributed to the natural ageing-related health deterioration), others can remain stable for years. Identifying risk factors for accelerated health decline in persons with multimorbidity could help prevent complications and reduce unnecessary interventions. Our review, therefore, aims to map the evidence on the clinical, biographical and healthcare-related factors associated with an accelerated health decline in multimorbid individuals.

We will use the evidence-mapping review methodology. We will perform a systematic comprehensive literature search in Medline via Pubmed, Cochrane Library, EMBASE, Web of Science and Google Scholar using two broad concepts: ‘multimorbidity’ and ‘longitudinal studies’. We will search with MeSH terms (eg, ‘Multimorbidity’ (Majr), ‘Longitudinal Studies’ (Majr)) and free text words (eg, multimorbidity, multiple chronic condition*, longitudinal), from inception to date of the final search. All original quantitative studies involving participants in primary care and related healthcare settings will be included. Abstract/titles and full-text screening and data extraction will be performed independently by two or more researchers to minimise selection and reporting bias, with conflicts resolved by consensus. The data will be analysed qualitatively, and topics will be extracted to create evidence clusters. Risk factors will be classified in groups and cross-referenced against the outcomes from respective studies into combinations of exposure-outcome clusters. The resulting evidence clusters will be described narratively and presented as bubble plots. The search, initiated in January 2023, will be updated following this protocol review to reflect the most current evidence; exact dates will be reported in the results manuscript.

Due to the nature of the proposed evidence map, ethics approval will not be required. Results from our research will be disseminated through publications in peer-reviewed journals and presentations at local, national and international conferences.

https://osf.io/q72xa/

Oral HIV pre-exposure prophylaxis (PrEP) is a highly effective biomedical intervention for HIV prevention, but its access and utilisation are challenging, especially in high-burden settings such as Kenya. For potential PrEP users, long delays and repeated consultations with several providers are obstacles to both PrEP uptake and continuation. The One-Stop PrEP Care project aims to promote the use of PrEP among clients in the health system and enhance client satisfaction by reducing the waiting time.

We are conducting a 1:1 cluster-randomised trial to evaluate whether One-Stop PrEP Care achieves equivalent or better PrEP outcomes compared with the standard of care model in 12 high-volume HIV clinics in Kisumu County, Kenya. In the One-Stop model, all core PrEP components, including HIV risk evaluation, HIV testing and PrEP dispensing, are provided by one provider in a single consultation room. Programme data from ≥2400 new PrEP clients will be abstracted for 12 months each to obtain primary endpoints of PrEP initiation and continuation. Adherence will be assessed via blood drug level testing. A nested cohort of up to 300 PrEP clients will be enrolled and followed every 3 months to provide in-depth data on individual HIV prevention behaviour, risk perception and how they align PrEP use with perceived risk. We will also evaluate programme costs.

Ethical approval was obtained from the University of Washington Institutional Review Board (IRB) on 8 July 2022 (IRB ID: STUDY00015873) and the Kenya Medical Research Institute Scientific and Ethics Review Unit (SERU) with a letter dated 4 May 2023 (Ref: 4697). Project findings will be shared with stakeholders, including the Ministry of Health, County health officials and participants. Results will be disseminated through manuscripts, policy briefs and health meetings.

Plans for communicating important protocol modifications include timely notifications to all study team members and training on the changes, and updates to relevant stakeholders, including the two IRBs, through protocol amendment submissions.

V. 2.0 dated 21 May 2024.

NCT03194308.

Guideline-based strategies to prevent chronic kidney disease (CKD) progression and complications are available, yet their implementation in clinical practice is uncertain. We aimed to synthesise the available evidence on the concordance of CKD care with clinical guidelines to identify gaps and inform future CKD care.

Systematic review and meta-analysis.

We systematically searched MEDLINE (OVID), EMBASE (OVID) and CINAHL (EBSCOhost) (to 18 July 2025) for observational studies of adults with CKD reporting data on the quality of CKD care. We assessed data on quality indicators of CKD care across domains that related to patient monitoring (glomerular filtration rate and albuminuria), medications use (ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), statins) and treatment targets (blood pressure (BP) and HbA1c). Pooled estimates (95% CI) of the percentage of patients who met the quality indicators for CKD care were estimated using random effects model.

59 studies across 24 countries, including a total of 3 003 641 patients with CKD, were included. Across studies, 81.3% (95% CI: 75% to 87.6%) of patients received eGFR monitoring, 47.4% (95% CI: 40.0% to 54.7%) had albuminuria testing, and 90% (95% CI: 84.3% to 95.9%) had BP measured. ACEIs/ARBs were prescribed among 56.7% (95% CI: 51.5% to 62%), and statins among 56.6% (95% CI: 48.9% to 64.3%) of patients. BP (systolic BP ≤140/90 mm Hg) and HbA1c (

Current evidence shows substantial variation in CKD care quality globally. Guideline-concordant care varied according to quality measures and across patient groups, with gaps in indicators like albuminuria testing. These findings underscore the need for effective quality improvement strategies to address gaps in CKD care, including increased albuminuria testing for risk stratification, together with systematic measures for monitoring care quality.

CRD42023391749.