Childhood cancer presents significant challenges in low- and middle-income countries (LMICs), as survival rates remain substantially low. Supportive care, including nutritional support and infection prevention plus management, is crucial in improving outcomes of childhood cancer patients. To develop evidence-based interventions improving supportive care and survival, insight is needed into local prevalences of malnutrition, colonisation and infections, their association with clinical outcomes and the attitude of parents or legal guardians towards nutritional care and infection prevention. The overall aim of this prospective cohort study is to identify modifiable nutritional and infection-related determinants of clinical outcomes at 6 months in children with cancer (1–15 years of age) treated with curative intent at the Paediatric Oncology ward of the Shoe4Africa Children’s Hospital at the Moi Teaching and Referral Hospital in Eldoret, Kenya.

We will conduct a prospective cohort study on 150 children aged 1–15 years who are newly diagnosed with cancer and treated with curative intent. During 6 months of follow-up, we will collect clinical data, perform nutritional assessments and monitor pathogen exposure, colonisation and infections. Parents or legal guardians will receive one questionnaire to assess attitudes towards supportive care. Six-month mortality is the primary outcome. Other outcomes include the prevalence and characteristics of malnutrition, rectal colonisation with bacterial and fungal pathogens, infections and neutropenic fever episodes. Statistical analyses will include descriptive statistics, chi-square tests, logistic regression and thematic analysis.

The Institutional Research and Ethics Committee has approved the study protocol (FAN: 0004674, protocol version 1.0). Informed consent from parents or legal guardians and assent from children ≥12 years will be obtained. Findings will be disseminated through peer-reviewed publications, presentations at academic conferences and engagement with local and national policymakers and stakeholders. Data from this study could guide the development of locally informed, evidence-based supportive care interventions, with the ultimate goal to improve overall survival for children with cancer in LMICs.

Data on long-term outcomes after surgical repair of pulmonary valve stenosis are limited. This study evaluated survival, clinical outcomes and quality of life (QoL) after surgery during childhood.

Single centre, longitudinal cohort study evaluating consecutive patients with pulmonary valve stenosis who underwent surgical repair between 1968–1980 and were evaluated every decade since 1990.

Of the original cohort of 89 operated patients, 11 died (12%), including 2 who died within 30 days postsurgery (2%), and 7 (8%) were lost to follow-up. Survival at 50 years follow-up was 87%, which was not significantly different from the GDP. Of the remaining 71 survivors, 32 refrained earlier from participating in this cohort study, leaving 39 eligible, of whom 34 (87%) participated again (50% male, median age 48 years) with a median follow-up of 45 (range 40–52) years. Event-free survival was 50%, with supraventricular tachycardia (14%) and reintervention (13%) being the most frequent events, although less frequently in the last 10 years. At last follow-up, biventricular function was preserved in most patients. Reduced right and left ventricular ejection fraction (EF) was found in 33% and 13%, respectively. Exercise capacity and maximum rate of oxygen consumption were mildly impaired in 14% and 32% of patients. Patients who underwent an infundibulectomy during initial surgery were significantly more likely to undergo reintervention (HR=8.32, p=0.003). Patient-reported QoL scores remained stable over time and consistently exceeded those of the age-matched GDP.

Fifty-year survival after surgery for pulmonary valve stenosis was excellent and comparable to the GDP. Most patients maintained preserved ventricular function, functional capacity and excellent QoL. Routine lifelong follow-up may not be necessary for all patients, but should be considered for those who underwent an infundibulectomy or have residual lesions.

Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-accepted treatment for advanced Parkinson’s disease (PD). Currently, programming of the DBS is done in a trial-and-error manner and it can take up to 12 months to reach optimal stimulation parameters. Technological advances in electrode design and implantable pulse generator capabilities lead to an almost infinite number of stimulation options. To explore the potential benefit of all these technological advances, a conventional trial-and-error approach is no longer sufficient. Consequently, there is a clear need for a more computational approach to programming DBS systems. This pilot study is a prospective trial to prove the feasibility of programming bilateral STN-DBS for PD in a computational fashion based on patient anatomy, electrode position and brain connectivity. In this study, we aim to assess the safety, practical feasibility and technical feasibility of a computational approach for programming newly implanted STN-DBS patients with PD. This computational approach will be based on a patient-specific DBS setting regarding sweet spots and structural connectivity of the STN. The results of this pilot study will be used to develop a computational approach for DBS programming to use in a future randomised clinical trial.

The iDBS trial will be a prospective randomised feasibility study carried out at the Radboud university medical center. A total of 24 patients with PD eligible for bilateral STN-DBS surgery implanted with Boston Scientific Cartesia leads will be included. Patients will be randomised to receive either (1) computational DBS programming (n=12) or (2) conventional DBS programming based on monopolar review (n=12). The primary endpoints are safety (occurrence of stimulation-induced side effects, duration of induced side effects (temporary or permanent), severity of the stimulation-induced side effects) and technical feasibility (time from surgery to DBS initiation, time from surgery to reaching optimal DBS stimulation settings) of the computational workflow.

Ethical approval for this study has been granted by the Medical Ethical Committee region Arnhem-Nijmegen, the Netherlands (2024–17453). This study will be conducted in accordance with the Declaration of Helsinki and all applicable European and Dutch law. All participants will have to provide written informed consent. Results of the study will be submitted for publication in peer-reviewed journals and conferences.

The study is registered in the OMON-registry (NL87334.091.24, NL-OMON57446).

Selective fetal growth restriction (sFGR) is a major cause of perinatal morbidity and mortality in monochorionic diamniotic (MCDA) twin pregnancies. Current management relies on umbilical artery Doppler patterns in the smaller twin. These patterns are, however, inconsistent and do not represent a reliable severity scale, complicating clinical decision-making and parental counselling. This study aims to improve risk stratification by identifying predictors of adverse outcomes, while also evaluating the pathophysiology and multi-organ impact of sFGR in early childhood.

This is a prospective, international, multicentre cohort study conducted in six tertiary fetal medicine centres with expertise in complicated twin pregnancies. Recruitment began in March 2023 and will continue until December 2026, targeting 274 MCDA twin pairs with complete follow-up to develop a prediction model for adverse perinatal outcomes in sFGR at the time of diagnosis. Standardised data collection includes serial ultrasound examinations, advanced fetal imaging (cardiac, cerebral and 3D volumetric), fetal brain MRI and detailed placental phenotyping. Maternal and parental well-being are assessed during pregnancy and after birth. Neurodevelopmental outcome is evaluated up to 2 years after birth using validated tools. The statistical analysis plan includes predictive modelling with internal validation.

The study has been approved by the ethical review boards of all participating centres. Findings will be disseminated through peer-reviewed publications, international conferences and engagement with clinical guideline committees.

NCT05952583.

To examine differences in physical health conditions among female veterans compared with male veterans and female civilians.

Cohort analysis using data from the UK Biobank, incorporating self-reported and hospital-derived health information.

Veteran status was identified using Standard Occupational Classification codes. The study included female veterans (n=546), male veterans (n=2722) and female civilians (n=66 305).

Physical health conditions were identified through self-report and hospital records. Multivariable logistic regression models estimated associations between veteran status and selected health conditions, adjusting for age, sociodemographic factors, time in service, body mass index and current smoking status.

Compared with female civilians, female veterans had increased odds of chronic obstructive pulmonary disease (adjusted OR (aOR) 1.79, 95% CI 1.04 to 3.08) and lower odds of hypertension (aOR 0.74, 95% CI 0.59 to 0.93), with no significant difference in musculoskeletal conditions or osteoarthritis. Compared with male veterans, female veterans had significantly higher odds of osteoarthritis (aOR 1.61, 95% CI 1.25 to 2.08), migraine (aOR 2.63, 95% CI 1.66 to 4.19) and thyroid disorders (aOR 4.42, 95% CI 2.83 to 6.89).

Female veterans have distinct physical health profiles, including a greater burden of musculoskeletal and respiratory conditions compared with male veterans and female civilians. These findings highlight the need for targeted prevention and clinical interventions for women with a history of military service.

Effect size and event rate estimation is necessary for sample size calculation in randomised clinical trials. Overestimation of the effect size and event rate can lead to inadequately powered studies and increased probability of false negative results. This is common in trials involving critically ill patients. However, such overestimation has not been systematically evaluated in trials involving neurocritical care. We aimed to conduct a systematic review of published randomised clinical trials involving critically ill neurological patients, to determine the accuracy of effect size and event rate estimation.

We will review randomised clinical trials involving adult critically ill neurological patients that were published from 2015 onwards in selected clinically useful and high-impact journals. We will include randomised clinical trials reporting a binary or time to event outcome, using two study groups, and a superiority design testing the efficacy of diagnostic, monitoring, therapeutic or process interventions. All eligible studies must report an estimated event rate in the control group and estimated effect size. All relevant studies will be identified through database searches. All study selection and data extraction will be conducted by two independent reviewers. We will use a random-effects model for pooling data. This review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Accuracy of effect size and event rate estimation will be evaluated by comparing the estimated and observed values. The association between the accuracy of the individual randomised clinical trial effect size and event rate estimation and rejection of the null hypothesis will be evaluated using logistic regression analysis. Multivariable linear regression analysis will be used to explore the factors associated with accuracy of effect size and event rate estimation. In addition, we will perform subgroup analysis by impact factor of the published journals, sample size of the studies and risk of bias.

As this systematic review will use data from previously published studies, it does not require ethics approval. Findings of this systematic review will be published in a peer-reviewed journal and will be presented at specialty-based conferences. The study will be included in the higher degree research thesis of the primary author.

CRD420251106394.

Value-based healthcare (VBHC) strives to improve the healthcare system by focusing on value of care, that is, patient relevant outcomes relative to the costs for achieving these outcomes. Within VBHC, patient participation is crucial to identify patient relevant outcomes and value improvement potential. However, patient participation in VBHC initiatives remains limited. Therefore, we aimed to improve patient participation within VBHC teams with the ultimate aim to develop a practical guide for patient participation in VBHC.

An action research study.

This study was conducted in seven collaborating Dutch hospitals from March 2023 to November 2024.

Seven VBHC teams were selected to participate in the cyclical action research steps, that is, orientation, planning, implementation, and evaluation, in which patient participation was implemented or improved. These included the following patient groups: prostate cancer, vulnerable elderly, breast cancer, diabetes, maternity care, colorectal cancer and chronic kidney disease.

Both qualitative and quantitative data were collected. Qualitative data included observations and minutes of meetings with the intervention teams. Quantitative data included responses to the Public and Patient Engagement Evaluation Tool (PPEET) by multiple members of the intervention (n=7) and control teams (n=94) at three time points (T1=6 months, T2=12 months, T3=end of study). Qualitative data were thematically analysed and quantitative data were analysed descriptively. Finally, the data were triangulated to create an overview of lessons learnt in improving patient participation.

Patient participation goals varied across teams, leading to diverse actions, such as establishing a diabetes patient panel and distributing questionnaires to patients with colorectal cancer. PPEET results show that 71% of intervention team members reported that patient participation had an impact on the team’s outcomes compared with 44% in control teams (T3). Furthermore, 80% of the intervention team members initially wanted training in patient participation (T1), which dropped to 29% at T3. Overall, 22 lessons in improving patient participation in multidisciplinary project teams were identified and compiled into a practical guide.

The action research process improved the process and impact of patient participation in the intervention teams. Furthermore, the results indicate that the action research process enhanced the team members’ knowledge and skills on patient participation. The practical guide developed in this study can be used to support implementation of patient participation in VBHC.

Out-of-hospital cardiac arrest (OHCA) has low survival rates with worse outcomes at night due to delayed emergency medical services (EMS) response, resource limitations and workforce fatigue. Since randomised trials are unfeasible, all-comers registries provide essential data to bridge evidence gaps and improve EMS protocols.

Retrospective observational study using propensity score matching.

National EMS registry and death registry data from Poland, cases from September to November 2022.

Of 2388 eligible patients, cases were grouped by time of cardiac arrest (on-hours: 7:00–18:59; off-hours: 7:00–18:59 AM) and matched 1:1 using propensity scores, yielding 1194 pairs.

Primary: return of spontaneous circulation (ROSC) and 30-day survival.

Secondary: EMS response time.

Our findings revealed significant disparities in OHCA outcomes between day and night shifts. ROSC rates were notably lower at night (20.9% vs 34.8%; p=0.01); however, no difference in 30-day survival was observed (8.3% vs 8.1%; p=0.94). Furthermore, EMS response times were significantly longer during nighttime hours (median and IQR): 12.4 (7.4–14.6) versus 11.2 (6.2–13.5) (minutes); p=0.01.

Patients with OHCA during off-hours experienced longer EMS response times and significantly lower rates of ROSC as compared with daytime hours. No difference in 30-day survival was observed between groups. Potential contributors include reduced staffing, fatigue and logistical delays. System-level changes in EMS scheduling and workforce planning might help to reduce time-of-day-related disparities in OHCA outcomes.

Clinical Trials ID: NCT03130088; Post results

Alcohol dependence (AD) is highly prevalent and has severe consequences on health and quality of life. However, the efficacy of approved pharmacotherapies such as naltrexone (NTX) remains limited, highlighting the need for novel pharmacotherapeutic approaches. Cannabidiol (CBD) is a promising candidate, which has shown potential to reduce craving and alcohol use by modulating brain circuits involved in craving and addiction. Preclinical studies suggest that CBD may enhance NTX’s therapeutic effects.

This is a three-armed, randomised, double-blind, placebo-controlled parallel group, multicentre phase II clinical trial. A total of 150 patients with AD will be randomised (1:1:1) to receive either 800 mg or 1200 mg CBD plus 50 mg oral NTX or placebo plus 50 mg oral NTX for 14 days. Alcohol craving will be assessed using the Obsessive Compulsive Drinking Scale (OCDS-G) where the primary endpoint is the change from baseline to the end of treatment. Secondary outcomes include craving during the entire study, quality of life, depressive symptoms, anxiety, patient-reported outcomes, neural brain activation, CBD plasma levels, time to relapse, alcohol use and treatment safety. For the comparison of each experimental group to the control group, a strata-adjusted (centre and baseline OCDS-G) van Elteren test is applied with adjustment for multiple testing by Bonferroni-Holm.

The trial has been approved by the Ethics Committee and the competent authority (ID: B_03510). All participants will provide written informed consent. An independent Data and Safety Monitoring Board will monitor safety. This trial complies with national and international regulations.

NCT06845124; EU Trial Number: 2024-518164-12-00.

This study aimed to develop a core outcome set (COS) for trials evaluating the effects of complementary therapies in people with multiple sclerosis (pwMS). We sought to identify the outcomes most relevant to pwMS, their relatives and friends, healthcare professionals and researchers and to propose these for inclusion in future trials.

A participatory international research project using a mixed-method approach with qualitative and quantitative methods. The study included a scoping review and a national survey in Switzerland to identify candidate outcomes, followed by an international COS survey to rate the importance of these outcomes. The final phases involved two consensus meetings to refine and finalise the COS.

Data were sourced from the published literature and input from international stakeholders.

pwMS and other relevant stakeholders, including their relatives and friends, healthcare professionals and researchers.

A total of 770 individuals participated in the international COS survey of 39 candidate outcomes (662 pwMS, 27 relatives/friends, 58 healthcare professionals and 23 researchers). According to the survey results, 13 outcomes were added to the COS, 5 were excluded and 21 were classified as ‘no consensus’. 13 individuals (six pwMS, one pwMS’s friend, three healthcare professionals and three researchers) attended the first consensus meeting. Following the voting on the outcomes without consensus, seven outcomes were added to the COS, four were excluded and 10 outcomes were still classified as ‘no consensus’. The six members of the stakeholders advisory board (one pwMS, four healthcare professionals and two researchers) attended the second consensus meeting to define the final COS. Nine additional outcomes were included in the COS. Sexual problems, an outcome previously excluded, were also added. In total, 30 outcomes were included in the final COS.

We have developed the first COS for future trials of complementary therapies for pwMS. The use of this COS will promote that future research in complementary therapies is relevant for pwMS and other stakeholders involved in MS care. Future COS research should integrate diverse geographical regions, where perspectives and access to complementary therapies may vary.

https://osf.io/ys7xt/.