The incidence of anal carcinoma is increasing, with the current gold standard treatment being chemoradiotherapy. There is currently a wide range in the radiotherapy dose used internationally which may lead to overtreatment of early-stage disease and potential undertreatment of locally advanced disease.

PLATO is an integrated umbrella trial protocol which consists of three trials focused on assessing risk-adapted use of adjuvant low-dose chemoradiotherapy in anal margin tumours (ACT3), reduced-dose chemoradiotherapy in early anal carcinoma (ACT4) and dose-escalated chemoradiotherapy in locally advanced anal carcinoma (ACT5), given with standard concurrent chemotherapy.

The primary endpoints of PLATO are locoregional failure (LRF)-free rate for ACT3 and ACT4 and LRF-free survival for ACT5. Secondary objectives include acute and late toxicities, colostomy-free survival and patient-reported outcome measures. ACT3 will recruit 90 participants: participants with removed anal tumours with margins ≤1 mm will receive lower dose chemoradiotherapy, while participants with anal tumours with margins >1 mm will be observed. ACT4 will recruit 162 participants, randomised on a 1:2 basis to receive either standard-dose intensity modulated radiotherapy (IMRT) in combination with chemotherapy or reduced-dose IMRT in combination with chemotherapy. ACT5 will recruit 459 participants, randomised on a 1:1:1 basis to receive either standard-dose IMRT in combination with chemotherapy, or one of two increased-dose experimental arms of IMRT with synchronous integrated boost in combination with chemotherapy.

This study has been approved by Yorkshire & The Humber – Bradford Leeds Research Ethics Committee (ref: 16/YH/0157, IRAS: 204585), July 2016. Results will be disseminated via national and international conferences, peer-reviewed journal articles and social media. A plain English report will be shared with the study participants, patients’ organisations and media.

ISRCTN88455282.

Lumbar back myofasciitis (LBM) is a common condition caused by cold exposure, lumbar injuries or poor posture, leading to aseptic inflammation, fibrosis and chronic pain. While acupuncture stimulation of trigger points is widely used, clinical evidence supporting its efficacy remains limited. This study aims to evaluate the effectiveness and safety of acupuncture stimulation of trigger points in the treatment of LBM and to explore the underlying analgesic mechanisms.

This single-centre randomised controlled trial will be conducted at Acupuncture and Moxibustion Hospital of China Academy of Chinese Medical Sciences. A total of 60 participants will be randomly assigned to either the experimental group or the control group in a 1:1 ratio. The primary outcome measure will be the Visual Analogue Scale for pain, while secondary outcomes will include pressure pain threshold, ultrasound, infrared thermography and Roland-Morris Disability Questionnaire.

Ethics approval was obtained from the Ethics Committee of Xiyuan Hospital, China Academy of Chinese Medical Sciences (Approval No. 2024XLW007-2). The findings of this study will be published in peer-reviewed journals. Prior to participation, all eligible participants will be given informed consent.

ITMCTR2025000258.

International pilot projects focusing on next-generation sequencing in newborn screening (NBS), that is, genomic NBS (gNBS), have been established thanks to continuous therapeutic progress and the massive development of new genetic technologies with rapidly decreasing costs. Given the highly encouraging results of the French SeDeN project regarding anticipated acceptability among professionals and parents, it is now appropriate to launch a similar pilot project in France, in collaboration with other international initiatives under the International Consortium on Newborn Sequencing framework.

PERIGENOMED is a large-scale project designed to provide the first concrete evidence on the relevance of gNBS in France. It includes two clinical trials. We present here the design chosen for the first clinical trial (PERIGENOMED-CLINICS 1). PERIGENOMED-CLINICS 1 aims to assess the feasibility, real-world acceptability, psychosocial impact and organisational pathways of panel-based genomic newborn screening in France, involving 2500 participants. Solo-GS targeting two lists of gene–disease dyads responsible for treatable (list 1; 400 genes, 171 diseases/group of diseases) or actionable (list 2 optional; 407 genes, 218 diseases/group of diseases) rare and severe early-onset diseases will be proposed in five health institutions. Ancillary social and impact studies will also be included.

All study procedures have been reviewed and approved by relevant French ethics committees and regulatory authorities (CPP Est II-2024-A02224-43, 1 January 2025). Results of the project will be disseminated through peer-reviewed publications, national and international conferences, and public engagement initiatives, in coordination with stakeholders.

NCT06875089.

Post-stroke patients with sarcopenia commonly exhibit impaired postural control and balance, which elevates fall risk and diminishes quality of life. This study investigates if combining Tai Chi with Dynamic Neuromuscular Stabilization (DNS) has synergistic benefits for neuromuscular control, core stability and balance in post-stroke patients with sarcopenia. Tai Chi enhances dynamic balance and lower limb strength through controlled weight-shifting movements. In contrast, DNS aims to restore neuromuscular synergy and regulate intra-abdominal pressure. It applies principles from developmental kinesiology. This study seeks to determine whether the combined intervention demonstrates significantly greater improvements in postural stability relative to isolated interventions or conventional rehabilitation approaches.

A single-blind randomised controlled trial will recruit 60 post-stroke patients with sarcopenia, randomly allocated into four groups: Tai Chi, DNS, Tai Chi+DNS and a control group (receiving conventional rehabilitation). Interventions will be conducted over 5 weeks, with primary outcomes evaluated using the Berg Balance Scale and Trunk Impairment Scale. Secondary outcomes comprise metrics from the Balance Manager System, 30-second Chair Stand Test, Timed Up and Go Test, bioelectrical impedance-derived phase angle, Modified Falls Efficacy Scale and Geriatric Depression Scale-Short Form.

The Ethics Committee of the Second Rehabilitation Hospital of Shanghai has approved this study. The findings will be distributed by publication in indexed journals and presentation at global academic forums.

ChiCTR2500102577.

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.

This study aims to assess the feasibility of respondent-driven sampling (RDS) to recruit participants with recent abortion experiences in humanitarian contexts, and describe the composition of the study sample generated with this sampling method.

This was a three-phase mixed-methods community-engaged research study employing an exploratory and explanatory sequential approach. We conducted in-depth interviews, focus group discussions, an interviewer-administered questionnaire on abortion experiences and a health facility assessment.

Bidibidi Refugee Settlement, Uganda and Kakuma Refugee Camp, Kenya from November 2021 to December 2022.

Using RDS, we recruited 600 participants in Kakuma and 601 participants in Bidibidi with recent abortion experiences. In Kakuma, participants were primarily from Burundi, the Democratic Republic of the Congo and South Sudan; participants in Bidibidi were primarily from South Sudan. Most participants in both sites had completed at least some primary school and were not employed.

RDS recruitment dynamics: convergence and bottlenecks on key sociodemographic variables, recruitment and population homophily, reciprocity of social ties, success and experiences recruiting.

There were minor violations of RDS assumptions, particularly regarding assumptions of reciprocity of ties and seed composition independent of sample. In addition, there was a strong tendency of participants to recruit those from the same home country and living within the same camp zone. However, sample proportions for age, home country, marital status, zone of residence and student status reached equilibrium (stabilised) by around 500 participants at each site, and we were able to quickly attain the study sample size.

While the true representativeness of our sample remains unknown, RDS is a practical and effective recruitment method in humanitarian contexts for sensitive topics, particularly for research questions in which no data or sampling frames exist. However, attention to representativeness and community engagement is essential to optimising its application and ensuring success.

To evaluate the association between the stress hyperglycaemia ratio (SHR) and baseline stroke severity in patients with acute ischaemic stroke (AIS) and to investigate whether the relationship is non-linear.

Retrospective cohort study.

A tertiary hospital in Zhejiang Province, China.

1479 consecutive AIS patients admitted within 24 hours of symptom onset between 2016 and 2022.

SHR was calculated as fasting plasma glucose (mmol/L) divided by glycated haemoglobin (HbA1c, %). Stroke severity was assessed by the NIH Stroke Scale (NIHSS) and categorised as mild (NIHSS ≤5) or moderate to severe (NIHSS >5). Associations between SHR and stroke severity were examined using multivariable logistic regression, generalised additive models and threshold effect analysis.

Patients with more severe strokes had significantly higher SHR values (median 0.99 vs 0.94; p

SHR is independently associated with greater stroke severity at admission. Values below 1.3 may reflect heightened metabolic stress and could help inform early risk stratification in AIS management, but their discriminative power is limited and should be interpreted in conjunction with other clinical indicators.

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.

Sickle cell disease (SCD) is due to the mutation of haemoglobin (Hb), from HbA to HbS and characterised by recurrent vaso-occlusive crises (VOC), which can progress to acute chest syndrome (ACS), a leading cause of death in adults with SCD. Hypoxia is a key modifiable factor in the polymerisation of HbS and the pathogenesis of VOC. High-flow nasal oxygen (HFNO) delivers humidified gas at high oxygen concentrations and flow rates: the former may reverse sickling (metabolic effect) to accelerate VOC resolution and prevent ACS, while the latter may reduce the risk of ACS by mitigating hypercapnia and generating positive airway pressure that limits hypoventilation and atelectasis (pulmonary effect). The study hypothesises that HFNO is a safe and effective strategy for treating VOC and preventing secondary ACS, and will assess this using a multi-arm multi-stage (MAMS) trial design.

This is a prospective, multicentre, randomised, open-label controlled trial following an MAMS design with three phases and four arms: one control (low-flow oxygen) and three HFNO intervention arms with varying fraction of inspired oxygen levels (low, intermediate, high). The pilot stage will assess safety and feasibility, using the rate of cardiac and neurological events as the primary endpoint. In the activity stage, arms demonstrating acceptable safety will be compared for efficacy based on the rate of VOC resolution without complications by day 5, allowing selection of the most promising arm. The final efficacy stage will compare the selected HFNO strategy to control, with prevention of secondary ACS by day 14 as the primary endpoint. The study aims to enrol up to 350 VOC episodes in total.

The study has been granted ethical approval (CPP SUD MEDITERRANEE IV). Following the provision of informed consent, patients will be included in the study. The results will be submitted for publication in peer-reviewed journals.

NCT03976180.

This study aimed to evaluate the cost-effectiveness of integrating nutritional support into India’s National Tuberculosis Elimination Programme (NTEP) using the MUKTI initiative.

Economic evaluation.

Primary data on the cost of delivering healthcare services, out-of-pocket expenditure and health-related quality of life among patients with tuberculosis (TB) were collected from Dhar district of Madhya Pradesh, India.

Integration of nutritional support (MUKTI initiative) into the NTEP of India.

Routine standard of care in the NTEP of India.

Incremental cost per quality-adjusted life year (QALY) gained.

A mathematical model, combining a Markov model and a compartmental susceptible–infected–recovered model, was used to simulate outcomes for patients with pulmonary TB under NTEP and MUKTI protocols. Primary data collected from 2615 patients with TB, supplemented with estimates from published literature, were used to model progression of disease, treatment outcomes and community transmission dynamics over a 2-year time horizon. Health-related quality of life was assessed using the EuroQol 5-Dimension 5-Level scale. Costs to the health system and out-of-pocket expenditures were included. A multivariable probabilistic sensitivity analysis was undertaken to estimate the effect of joint parameter uncertainty. A scenario analysis explored outcomes without considering community transmission. Results are presented based on health-system and abridged societal perspectives.

Over 2 years, patients in the NTEP plus MUKTI programme had higher life years (1.693 vs 1.622) and QALYs (1.357 vs 1.294) than those in NTEP alone, with increased health system costs (11 538 vs 6807 (US$139 vs US$82)). Incremental cost per life year gained and QALY gained were 67 164 (US$809) and 76 306 (US$919), respectively. At the per capita gross domestic product threshold of 161 500 (US$1946) for India, the MUKTI programme had a 99.9% probability of being cost-effective but exceeded the threshold when excluding community transmission.

The findings highlight the potential benefits of a cost-effective, holistic approach that addresses socio-economic determinants such as nutrition. Reduction in community transmission is the driver of cost-effectiveness of nutritional interventions in patients with TB.

Traumatic brain injury (TBI) often causes permanent neurological dysfunction. Although no medication has been validated yet to prevent secondary injury of brain tissue, recent animal studies have reported that perampanel, a glutamine receptor antagonist, could improve the neurological functions of animals with TBI by mitigating the abnormal calcium influx and cell death around the site of primary injury. The present study aims to elucidate the efficacy of perampanel administration in improving the neurological function of patients with TBI.

The perampanel for alleviation of secondary injury in TBI trial is a multicentre, phase-II, open-label randomised controlled trial targeting patients with mild-to-moderate TBI. This trial will include adult TBI patients with a Glasgow Coma Scale score of 9–14 from five tertiary centres. Patients with epilepsy as a comorbidity, delayed presentation of symptoms (>24 hours after injury) or Injury Severity Score of ≥25 will be excluded. The study participants will be randomly assigned to either the perampanel group (2 mg/day) or the control group (fosphenytoin administered at a dose of 15–18 mg/kg/day, followed by 5–7.5 mg/kg/day of fosphenytoin). In both groups, the medication will be initiated within 12 hours of the TBI diagnosis and continued for 7 days. The antiepileptic drugs can be increased, changed or added as necessary if early post-traumatic seizures are observed. The primary outcome is favourable neurological outcome, defined as a Glasgow Outcome Scale Extended score of ≥5 at 90 days after the TBI diagnosis, which will then be compared between the groups through an intention-to-treat analysis.

The present study has been approved by the Certified Review Board of Keio at the principal institution (approval number: N20240004). Written informed consent will be obtained from all participants or their legal representatives. The results will be disseminated via publications and presentations.

Japan Registry of Clinical Trials (jRCTs031250067).

Transitions from the emergency department (ED) to home are high-risk periods for medication-related harm. Pharmacist-led interventions during this period may improve medication safety and care continuity, yet co-design approaches to develop such interventions remain underused. The aim of this study is to co-design a pharmacist-led transition of care programme for patients discharged from the ED.

This study will be conducted at a 371-bed secondary-care teaching hospital in Qatar and will follow two sequential phases using qualitative and participatory methods. Phase I will involve focus groups and semistructured interviews with key stakeholders (clinical pharmacists, physicians, nurses and patients or patient representatives). Phase II will consist of an intervention co-design workshop with decision makers (leaders, policymakers and representatives from Phase I). Participants will be recruited using purposive and snowball sampling. Interviews will be audio recorded and transcribed verbatim. Data will be analysed using an inductive-deductive approach, guided by the Theoretical Domains Framework, the Care Transitions Framework and the APEASE (Affordability, Practicability, Effectiveness/cost-effectiveness, Acceptability, Side-effects/safety, Equity) criteria for evaluation of intervention feasibility.

The anticipated outcome is a prototype intervention detailing target recipients, core components, workflow, implementation strategies and supporting tools. This prototype will be pilot-tested to assess feasibility and inform further refinement.

The study was approved by the Medical Research Centre of Hamad Medical Corporation-Qatar (MRC-01-24-699) and Qatar University Institutional Review Board (QU-IRB 009/2025-EM). Written informed consent will be obtained from all study participants prior to participation. Research findings will be disseminated through institutional stakeholder briefings, presentations at national and international scientific conferences and publication in peer-reviewed journals. Patient representatives will contribute throughout the intervention development process.

To explore the feasibility and acceptability of pain management (transcutaneous electrical nerve stimulation (TENS)) and patient education (PE) to increase physical activity in people with peripheral arterial disease and intermittent claudication (IC).

Feasibility randomised controlled trial with embedded process evaluation.

One secondary care UK vascular centre.

56 community-dwelling adults with a history of stable IC and ankle-brachial pressure index ≤0.9 were recruited via claudication clinics.

Participants randomised to 6 weeks of: TENS+PE, TENS, Placebo TENS+PE or Placebo TENS. PE was a 3-hour workshop plus three follow-up phone calls. The TENS machine was worn during walking (TENS: 120 Hz, 200 μs, intensity ‘strong but comfortable’; Placebo TENS: intensity below sensation threshold).

Primary feasibility outcomes included rates of recruitment, retention and adherence. Acceptability of the intervention and trial procedures was explored with semistructured interviews. Measures of walking capacity, walking behaviour, quality of life, disease perception and pain were recorded at baseline, end of intervention (6 weeks) and follow-up (3 months).

56 participants were randomised from 95 who completed baseline screening. Of the 39 excluded, 97% (38/39) had >20% variability in absolute claudication distance. All participants received their allocated intervention. Outcome completion was 91% at 6 weeks and 80% at 3 months. Attendance at group education was 96% with 63% taking follow-up phone calls. Compliance with TENS was 70% according to participant-completed logs. Interviewed participants (n=9) were generally positive about the acceptability of the interventions and trial procedures; however, experience of TENS use was mixed. Some participants were dissatisfied with the size of the device and electrode wires.

The PrEPAID (Pain management and Patient Education for Physical Activity in Intermittent claudication) trial was feasible to run; however, 40% of potential participants were excluded at screening due to issues of research fidelity rather than participant suitability or willingness to participate. A future definitive trial should consider a revised primary outcome measure and smaller wireless TENS machines.

ClinicalTrials.gov, NCT03204825. Registered on 2 July 2017.

Chief Scientist Office, Scottish Government. Translational grant award (TCS/16/55).

Migrants and refugees with low language proficiency (LLP) in the dominant language of their host country have a higher risk of suffering from certain mental health disorders compared with non-migrant populations. They are also more likely to experience a lack of access to mental healthcare due to language-related and culture-related barriers. As part of the MentalHealth4All project, a digital multilingual communication and information platform was developed to promote access to mental healthcare for LLP migrants and refugees across Europe. This paper describes the study protocol for evaluating the platform in practice, among both health and/or social care providers (HSCPs) and LLP migrants and refugees.

We will conduct a pretest–post-test cross-national survey study to evaluate the platform’s effect evaluation (primary objective) and process evaluation (secondary objective). The primary outcomes (measured at T0, T2 and T3) are four dimensions of access to mental healthcare services: availability, approachability, acceptability and appropriateness of mental healthcare. Secondary outcomes (measured at T2) are: actual usage of the platform (ie, tracking data), perceived ease of use, usefulness of content, comprehensibility of information, attractiveness of content and emotional support. Participants will be recruited from nine European countries: Belgium, Germany, Italy, Lithuania, the Netherlands, Poland, Slovakia, Spain and the UK. Using convenience sampling through professional networks/organisations and key figures, we aim to include at least 52 HSCPs (ie, 6–10 per country) and 260 LLP migrants (ie, 30–35 per country). After completing a pretest questionnaire (T0), participants will be requested to use the platform, and HSCPs will participate in an additional personalised training (T1). Next, participants will fill out a post-test questionnaire (T2) and will be requested to participate in a second post-test questionnaire (T3, about 6–8 weeks after T2) to answer additional questions on their experiences through a brief phone interview (T3 is optional for migrants/refugees).

For all nine countries, the ethical review board of the participating university (hospital) has assessed and approved the protocol. If successful, the MentalHealth4All platform will be made publicly available to help improve access to mental healthcare services, as well as HSCPs’ cultural competencies in delivering such services, for any LLP migrants and refugees across Europe (and beyond). Findings will also be disseminated through peer-reviewed journals and conferences.

The ‘MHealth4All project’ was prospectively registered on Open Science Framework, DOI: 10.17605/OSF.IO/U4XSM.

Amoxicillin is recommended for children with uncomplicated severe acute malnutrition (SAM). However, some trials have shown no difference in amoxicillin for nutritional recovery in children with SAM compared with placebo. In addition, amoxicillin treatment requires two times per day dosing for 7 days, which may influence adherence. Azithromycin is a broad-spectrum antibiotic that can be provided as a single dose and has reduced mortality in children aged 1–59 months when provided by mass drug administration. The AMOUR trial is designed to assess amoxicillin, azithromycin and placebo as part of outpatient treatment of uncomplicated SAM.

This double-masked randomised controlled trial will enrol 3000 children over 3 years in an individually randomised 1:1:1 allocation to azithromycin, amoxicillin or placebo arms and follow them for 12 months. Children eligible to enrol in the study will be aged 6–59 months and have uncomplicated non-oedematous SAM as defined by weight-for-height Z-score

Ethical approval was obtained from the Institutional Review Board at the University of California, San Francisco (Protocol 23–39411) and the Comité d’Ethique pour la Recherche en Santé in Ouagadougou, Burkina Faso (Protocol 2024-01-08). The results of this study will be disseminated to the Ministry of Health, community stakeholders and via peer-reviewed publications and academic conferences.

NCT06010719.