Iron-folic acid (IFA) supplementation in pregnancy is recommended by the WHO, with a dose of 60 mg of iron in contexts where anaemia remains a severe public health problem. Iron-containing supplements may cause side effects that affect acceptability and adherence in a dose-response manner. Maternal multiple micronutrient supplements (MMS), which include iron and folic acid plus additional micronutrients, are also recommended in the context of rigorous research, and programmes are considering transitioning from IFA to MMS containing 30 mg of iron. We will evaluate the effect of iron dose in MMS on maternal acceptability, side effects, adherence and preferences.

The Multiple Micronutrient Supplementation (MMS) Iron Dose Acceptability Crossover Trial is an individually randomised, quadruple-blind, non-inferiority crossover trial of daily antenatal MMS supplementation formulations that contain 60 mg, 45 mg and 30 mg elemental iron among pregnant women in Dar es Salaam, Tanzania. A total of 156 pregnant participants will be randomised to a sequence in which they receive each of the three MMS formulations for 1 month. Participants, investigators, outcome assessors and data analysts will be blinded to the treatment sequence. The primary trial outcome is participant-reported acceptability of each MMS formulation, measured on a Likert scale. Secondary and tertiary outcomes include preferred and least preferred formulation, identification of MMS formulation, reported side effects and adherence assessed by pill count. Regression analyses will be used to assess differences between formulations and will account for sequence and period effects of the crossover trial design. Qualitative in-depth interviews from a subsample of participants will be conducted to understand women’s perceptions and experiences taking the different MMS formulations.

The trial protocol was approved by Harvard T. H. Chan School of Public Health Institutional Review Board (IRB), the Ifakara Health Institute IRB, the Muhimbili University of Health and Allied Sciences IRB, the National Health Research Ethics Sub-Committee and the Tanzania Medicine and Medical Device Authority. Results will be shared through publications and presentations at the local, regional and international levels.

ClinicalTrials.gov Identifier: NCT06069869.

The global burden of cancer is increasingly concentrated in low-income and middle-income countries (LMICs), where health systems face significant challenges such as late-stage diagnosis, limited resources and restricted access to specialised care. Palliative care plays a vital role in improving symptom control and quality of life for patients with cancer, particularly as care delivery shifts toward ambulatory and community-based settings. In this context, patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) are crucial for capturing patients’ perspectives on the quality of care. However, the use and characteristics of these instruments in ambulatory palliative care settings within LMICs remain poorly understood. This systematic review aims to identify and map PROMs and PREMs used among adult patients with cancer receiving ambulatory palliative care in LMICs, and to examine their content, psychometric properties and alignment with key domains of quality palliative care.

This systematic review protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA) guidelines. The search will be conducted across seven databases from the database inception to December 2025. Two independent reviewers will screen titles, abstracts and full-text articles using Rayyan software to identify studies involving adults (≥18 years) with cancer in ambulatory palliative care settings. Data extraction will capture study characteristics, instrument content and psychometric properties. The final review will be reported in accordance with the PRISMA-COSMIN for Outcome Measurement Instruments. A narrative synthesis will be conducted, mapping the identified instruments against the eight domains of the National Consensus Project Clinical Practice Guidelines for Quality Palliative Care to identify measurement gaps and inform future instrument development. A meta-analysis will be conducted if sufficient homogeneity exists.

This review will include only published data; therefore, no approval is required. The findings of this review will be presented at conferences and published in an open-access peer-reviewed journal.

CRD420251273579.

Anaemia is highly prevalent among the indigenous population globally. Several interventions have been used to prevent and manage nutritional anaemia, including dietary measures, health education, oral iron supplements, food fortification and intravenous iron therapy. This protocol describes a systematic review and meta-analysis to assess the effectiveness of interventions for the prevention and treatment of nutritional anaemia in indigenous populations worldwide.

The review will include randomised controlled trials, quasi-experimental studies and observational studies evaluating interventions, including but not limited to iron and folic acid supplementation, dietary modifications, food fortification, deworming and health education. A robust search strategy will be developed, and six electronic bibliographic databases and Google Scholar will be searched from 2000 to 2025. Two reviewers will independently screen the identified studies, extract data, conduct a critical appraisal and evaluate quality using the Joanna Briggs Institute tool. Based on the level of heterogeneity, a meta-analysis will be conducted using either a fixed-effect or random-effects model, with pooled estimates, and 95% CIs. The I² statistic will be used to evaluate heterogeneity. When meta-analysis is not feasible, narrative synthesis will be conducted. The impact of the intervention type and delivery model will be investigated using subgroup analysis.

This systematic review has been registered with PROSPERO. Ethical approval is not required as the study does not collect primary data from participants. The findings will be communicated via peer-reviewed journal articles and presentations at national and international conferences.

CRD420251120554.

Treatment with bevacizumab achieves both tumour stabilisation or regression and preservation or improvement of hearing. However, the efficacy of bevacizumab varies between patients and within patients. Side effects due to bevacizumab treatment are also common. It would be of value to predict therapeutic response prior to initiating therapy to prevent unnecessary exposure in patients unlikely to benefit.

We aim to recruit 25 patients with NF2-related schwannomatosis (NF2) with bilateral vestibular schwannomas. Patients will receive an intravenous injection of 37 MBq [⁸⁹Zr]bevacizumab followed by positron emission tomography (PET)/CT imaging 4 days later. After clinical evaluation at baseline, patients undergo bevacizumab treatment and are followed up at 3 and 6 months. The primary objective is to examine associations between pretreatment [⁸⁹Zr]bevacizumab uptake on PET/CT and changes in multiple hearing outcomes and radiological characteristics of the target tumour following treatment. Secondary outcome measures include vestibular functioning, patient reported outcome measures, cranial nerve functionality, peripheral neurology, non-target schwannoma response and renal function. Given the explorative nature of the study, associations between PET-derived metrics and clinical and radiological outcomes will be examined without formal hypothesis testing, using generalised estimating equations to account for within-patient correlation. Pairwise associations will be summarised in an association matrix with multiplicity addressed using an all-resolutions inference approach, and findings will be considered hypothesis generating.

This study was submitted via the Clinical Trials Information System reviewed and approved by the Medical Research Ethics Committee Leiden–The Hague–Delft Delft. The study findings will be disseminated through publication in peer-reviewed scientific journals and by presentation at national and international conferences.

The trial is registered at ClinicalTrials.gov Protocol Registration and Results System under the registration ID: NCT05685836.

Waiting for cardiac surgery is a stressful life event for most patients. Exploring what people experience while waiting and understanding their preferences and views on how waiting time could be improved will help to inform new strategies for more efficacious waiting list management. In this study, we explored experiences and views of people waiting for elective cardiac surgery across four major London hospitals.

Mixed-methods cross-sectional survey, with explanatory concurrent design.

Four cardiac surgery services across two National Health Service Trusts in London.

Patients on waiting lists for elective cardiac surgery at Royal Brompton, Harefield, St Thomas and King’s College hospitals between October 2023 and March 2024.

Experience of waiting for surgery, and preferences about how waiting time could be improved.

554 out of 1041 invited participants agreed to participate (recruitment rate 53.2%). Among them, 274 fully completed the survey (completion rate 49.5%). Most participants (from 52.2% to 70.9%) reported their daily and social activities were impacted by their cardiac condition, and worrying was an ubiquitous feeling (reported by 86%). Psychological distress was reported differently across women and men (higher in women). Eight themes were identified: worrying, daily activities, family/friends and social activities, sexual life, waiting list experience and feelings, communication, most important factors for surgery and suggested improvements. Communication with the surgeon and clinical team, and regular updates on waiting list progress are suggested as crucial factors to alleviate stress, thus potentially improving the experience of waiting for the surgery.

This study highlights the importance of emotional support, clear communication, regular updates on waiting list progress and building trust with the clinical team to improve patient-centred care while waiting for elective cardiac surgery. This finding can offer valuable insights for managing waiting lists in other surgery waiting list contexts.

NCT05996640.

The implantable cardioverter defibrillator (ICD) is a cardiac device recommended for use to prevent the occurrence of sudden cardiac death (SCD) in post-myocardial infarction (MI) patients with reduced left ventricular ejection fraction (LVEF). The evidence informing this guidance comes from landmark trials that are now more than 20 years old. The risk-benefit profile of ICD for the contemporary target population may have changed substantially since then, which raises the question of whether there is evidence for sparing patients a procedure associated with potentially severe complications and high healthcare costs. A main part of the PRevention Of sudden cardiac death aFter myocardial Infarction by Defibrillator implantation (PROFID) project is the PROFID EHRA trial, which is supported by the European Heart Rhythm Association. PROFID EHRA is a European Union-funded, prospective, randomised, multi-centre, non-inferiority study designed to compare optimal medical therapy (OMT) alone to ICD with OMT, for post-MI patients with reduced LVEF. The study also describes economic evaluation methods to quantify the cost and health implications of using OMT alone in place of ICD implantation plus OMT in this group of patients.

The economic evaluation has been designed to conduct a pre-trial cost-effectiveness analysis (CEA) prior to the availability of trial data, followed by a within-trial cost-consequences analysis (CCA) and a long-term post-trial CEA, conducted from the National Health Service and Personal Social Service perspective in England. The pre-trial CEA uses simulation modelling informed by available evidence to assess the lifetime costs and quality-adjusted life years of OMT alone and ICD+OMT in post-MI patients with reduced LVEF at risk of SCD, as defined in the PROFID EHRA trial. The within-trial CCA is intended to summarise the health-related quality of life (HRQoL), healthcare resource use and associated costs observed during the PROFID EHRA trial follow-up period. The post-trial CEA updates the pre-trial model by incorporating contemporary evidence about the HRQoL and costs observed during the trial and the occurrence of those events and outcomes accruing during the trial follow-up period and projecting them into the expected lifetime of the patients. Sensitivity analyses are performed to assess the robustness of the CEA results with respect to both model assumptions and uncertainty in the value of the model input parameters. Finally, a value of information analysis will identify the key drivers of uncertainty surrounding the model conclusions regarding the optimal treatment strategy, establishing if further research may be required.

The PROFID EHRA trial, under legal sponsorship of Charité—Universitätsmedizin Berlin, Germany, received its first ethics approval by the Medicine Research Ethics Committee of the La Paz University Hospital in Madrid, Spain (reference number LHS-2019-0209). Before including patients, for all participating study centres, the required local, central and/or national ethical approval has to be obtained. As of the date 13 November 2025, at least one participating study centre in the following countries has received ethical approvals from relevant ethics committees: Austria, Belgium, Czech Republic, Denmark, France, Germany, Great Britain, Hungary, Israel, the Netherlands, Poland and Spain. Results will be shared with the general public through various media channels and additionally with healthcare professionals and the scientific community through scientific meetings, conferences and publications.

NCT05665608.

Sleep, a fundamental element of health, accounts for about one-third of our lives, and is as crucial as nutrition and exercise. Among university students, medical students are one subset that seems particularly susceptible to sleep problems, perhaps due to the length and complexity of their studies and being under a high level of stress. Yoga Nidra has been studied as a therapeutic intervention for various medical conditions. The aim of the study is to evaluate the efficacy of short-duration Yoga Nidra for improving sleep quality in students at a tertiary healthcare centre in Rishikesh, Uttarakhand.

A two-group parallel randomised controlled trial will be conducted among undergraduate medical students with a Pittsburgh Sleep Quality Index (PSQI) score >5. Efficacy of short-duration Yoga Nidra in comparison to sleep education will be evaluated for PSQI scores, heart rate variability, respiratory rate, pulse rate, body mass index, blood pressure, random blood sugar, lipid profile, interleukin 6, salivary cortisol, generalised anxiety disorder and depressive disorder. The intervention will be pre-recorded with the duration of 12 min. The intervention group participants will receive three sessions per week for 4 weeks. The sample size is 160 students. All analyses will follow the intention-to-treat approach using SPSS V.26. Descriptive statistics, test of associations, parametric and/or non-parametric methods (as appropriate) will be used to assess within and between group changes.

The Institutional Ethics Committee (All India Institute of Medical Sciences (AIIMS), Rishikesh) has approved the study (#AIIMS/ie,C/22/231) and the trial has been prospectively registered in Clinical Trials Registry-India: CTRI/2022/07/044426. The results will be published in a peer-reviewed journal.

CTRI/2022/07/044426.

Mental health issues such as depression and anxiety are highly and disproportionally prevalent among university students. Beyond the academic rigour, stressors imposed by a new environment result in them being vulnerable to the onset and manifestation of mental health symptomatology. Leveraging smartphones and wearables for digital phenotyping capabilities is an innovative approach for monitoring and intervening in the mental health conditions of university students. This provides a unique opportunity to collect and identify digital and behavioural biomarkers, subsequently enabling the development of predictive models to identify university students at risk.

This study—Brightline—will employ an observational study design over a 6-month period, recruiting 500 students from a major public university in Singapore. Passive data collection will occur continuously throughout the monitoring period through a wearable device (Fitbit Charge 6) and smartphone sensors via the Brightline app, which uses a digital phenotyping data collection platform. Active data collection will consist of self-report questionnaires to be completed at the beginning of the study and follow-up assessments at 1, 3 and 6 months after. The passive and active data collected will be analysed to identify the digital biomarkers associated with depression, anxiety, stress, loneliness and affect among university students. Predictive models of these mental health issues will also be developed.

This study was approved by the Nanyang Technological University Institutional Review Board (IRB-2023-894). Findings from this study will be published in peer-reviewed journals and presented at academic conferences.

NCT06770075.

SARS-CoV-2 infection provides protection against reinfection and severe COVID-19 disease; however, this protective effect may diminish over time. We assessed waning of natural immunity conferred by previous infection against severe disease and symptomatic reinfection in Brazil and Scotland.

We undertook a test-negative design study and nested case–control analysis to estimate waning of natural immunity against severe COVID-19 outcomes and symptomatic reinfection using national linked datasets. We used logistic regression to estimate ORs with 95% CIs. A stratified analysis assessed immunity during the Omicron dominant period in Brazil.

We included data from the adult populations of Brazil and Scotland from 1 June 2020 to 30 April 2022.

Severe COVID-19 was defined as hospitalisation or death. Reinfection was defined as reverse-transcriptase PCR or rapid antigen test confirmed at least 120 days after primary infection.

From Brazil, we included 30 881 873 tests and 1 301 665 severe COVID-19 outcomes, and from Scotland, we included 1 520 201 tests and 7988 severe COVID-19 outcomes. Against severe outcomes, sustained protection was observed for at least 12 months after primary SARS-CoV-2 infection with little evidence of waning: 12 months postprimary infection: Brazil OR 0.12 (95% CI 0.10 to 0.14), Scotland OR 0.03 (95% CI 0.02 to 0.04). For symptomatic reinfection, Brazilian data demonstrated evidence of waning in the 12 months following primary infection, although some residual protection remained beyond 12 months: 12 months postprimary infection: OR 0.42 (95% CI 0.40 to 0.43). The greatest reduction in risk of SARS-CoV-2 infection was in individuals with hybrid immunity (history of previous infection and vaccination), with sustained protection against severe outcomes at 12 months postprimary infection. During the Omicron dominant period in Brazil, odds of symptomatic reinfection were higher and increased more quickly over time when compared with the overall study period, although protection against severe outcomes was sustained at 12 months postprimary infection (whole study: OR 0.12 (95% CI 0.10 to 0.14); Omicron phase: OR 0.15 (95% CI 0.12 to 0.19)).

Cross-national analyses demonstrate sustained protection against severe COVID-19 disease for at least 12 months following natural SARS-CoV-2 infection, with vaccination further enhancing protection. Protection against symptomatic reinfection was lower with evidence of waning, but there remained a protective effect beyond 12 months from primary infection.