The second phase of the Chiba Study of Mother and Child Health (C-MACH) was initiated to investigate how environmental exposures from the fetal period to early childhood influence maternal and child health outcomes. The sub-cohort focuses specifically on detailed assessments of indoor environmental factors and neighbourhood-built and social environments. By integrating environmental metrics with biological, behavioural and sociodemographic data, the study aims to elucidate their role in the development of allergies, neurodevelopmental disorders and other non-communicable diseases in early life.

Between June 2021 and April 2023, 505 pregnant women were enrolled in the second phase of the C-MACH main study. Of these, 298 participants consented to join the sub-cohort study, including 258 in the sleep and physical activity monitoring option (Option 1) and 148 in the indoor allergen exposure sub-study (Option 2). The study includes biological sampling, environmental monitoring and repeated questionnaire surveys. At baseline, 253 live births were recorded from 251 pregnancies.

Of the 298 women, 272 completed early pregnancy questionnaires. The mean maternal age was 33.1 years (SD 4.6); 97.8% were married. University-level education was reported by 51.0% of mothers and 53.7% of fathers. Most households had an annual income of 6 to

Longitudinal follow-up will continue until the children reach age 15. Future analyses will examine associations between environmental exposures and allergic, developmental, endocrine/metabolic and obesity-related outcomes.

China has a high disease burden of low bone mass, and elderly men with excessive alcohol consumption may be underdiagnosed and undertreated given the adverse effects on skeletal health. This study implemented an economic evaluation to assess the screening plus receiving anti-osteoporotic medication for low bone mass prevention in older men with excessive alcohol intake.

A patient-level Markov model.

Chinese men aged over 60 years with excessive alcohol consumption.

Receiving screening plus medication considered with two eligibility strategies for therapy: osteoporosis and osteopenia.

The quality-adjusted life-years (QALYs), lifetime cost and the incremental cost-effectiveness ratio (ICER) were calculated for different strategies relative to no screening. Scenario analyses were conducted to evaluate the cost-effectiveness associated with risk factors, study perspectives and selection of medication.

From the healthcare perspective, the prevention strategies for men aged over 70 years were cost-effective with the ICER of $28 403/QALY for osteoporosis and $24 560/QALY for osteopenia. Scenario analyses revealed screening strategies were cost-effective in men with risk factors aged over 60 years. In the selection of medication, denosumab might be dominant. From the societal perspective, prevention for osteopenia aged from 60 years was cost-effective at the ICER of $36 524/QALY.

These findings suggest that prevention strategies for Chinese older men with excessive alcohol consumption would be cost-effective. Early screening initiation will aid efforts in improving skeletal health for men with excessive alcohol intake in China and reducing humanistic and economic burdens.

Older adults with cancer have ageing-related vulnerabilities that influence their treatment tolerance and decision-making. In our previous randomised controlled trial (MAPLE), integrating geriatric assessment (GA) with communication support using a question prompt list (QPL), delivered by trained intervention providers, facilitated patient–oncologist communication, increased implementation of GA-guided management (GAM) and improved patient outcomes. However, its widespread adoption has been limited by the need for trained personnel and dedicated time. To enhance scalability and sustainability, we developed a mobile application-based intervention to deliver GAM and communication support. This MAPLE2 study aims to evaluate the feasibility of the intervention using this mobile application-based GA and QPL among older adults with cancer.

This multicentre, open-label, pilot randomised controlled trial will be conducted at two academic hospitals in Japan. Patients aged≥70 years with solid cancer or lymphoma initiating or changing systemic therapy will undergo baseline GA. Patients with any GA impairment will be randomised to receive either (1) a mobile application-based intervention providing feedback of GA summary with tailored GAM recommendations and QPL or (2) usual care. The primary endpoint is the proportion of participants who complete all of the following interventions using the mobile application: (1) self-administered GA, (2) receipt of the tailored GAM recommendations and QPL and (3) confirmation that their oncologists review the tailored GAM recommendations and QPL at subsequent visits. Forty participants are planned to be enrolled.

The study has been approved by the Institutional Review Board of the National Cancer Center, Japan (approval number: 2025-089). Written informed consent will be obtained from all participants. Results will be presented at academic conferences and published in peer-reviewed journals.

Recruitment has been initiated from 8 September 2025 and is planned to be completed by 31 August 2026, with a follow-up period by 31 August 2027.

UMIN000058887

Chronic respiratory diseases (CRDs), such as asthma and chronic obstructive pulmonary disease (COPD), are among the leading non-communicable diseases (NCDs) worldwide. However, diagnosing CRDs in low-income and middle-income countries (LMICs) remains challenging due to limited access to spirometry and trained professionals. Aggravating the burden, CRDs often coexist with other NCDs, increasing healthcare costs, reducing quality of life and elevating mortality. These challenges highlight the need for simple case-finding approaches for CRDs, such as the COPD in Low-Income and Middle-Income Countries Assessment (COLA-6) questionnaire, to support prompt identification and appropriate care within NCD services in LMICs.

To evaluate the discriminative accuracy, feasibility and implementation of the COLA-6 questionnaire in identifying and managing CRDs in Brazilian Primary Healthcare (PHC) services for NCDs.

The Multimorbidity Approach for REspiratory Solutions (MARES) study consists of three work packages to be conducted in PHC services in São Carlos/SP and São Paulo/SP, Brazil.

MARES-1: A cross-sectional observational study enrolling 859 individuals with at least one NCD receiving care in PHC. The COLA-6 questionnaire will be administered by the research team and compared with quality-assured spirometry. The Chronic Airways Assessment Test (CAAT), Asthma Control Questionnaire (ACQ-7) and fractional exhaled nitric oxide (FeNO) will also be assessed. The diagnostic performance of COLA-6 for identifying CRDs—including COPD, asthma, preserved ratio impaired spirometry, restriction and overlaps—will be assessed using area under receiver operating characteristic curves and 95% CIs.

MARES-2: A cross-sectional observational study enrolling 20 healthcare professionals (physicians, physiotherapists, community health agents and nurses) from five PHC services. These professionals will apply the COLA-6 during routine NCD care to a total sample of 1000 patients. Qualitative interviews will be conducted to explore barriers and facilitators to the implementation of COLA-6, using deductive thematic analysis.

MARES-3: A longitudinal, prospective observational study in which patients from MARES-1 and MARES-2 will be reassessed at 6-month follow-up. A total sample of 473 participants with abnormal spirometry, a diagnosis of CRD or high risk for CRDs is expected. Participants will undergo spirometry, and a subset will be interviewed to explore their healthcare experiences through qualitative thematic analysis. Access to diagnostic and treatment services in Brazil will be assessed. Changes in spirometry values, FeNO, CAAT and ACQ-7 scores from baseline to 6 months in patients from MARES-1 will be analysed.

This study has been approved by the Ethics Committees of Federal University of São Carlos and University of Santo Amaro (UNISA). Ethical approval was also granted by the University College London. Results will be disseminated through peer-reviewed medical journals and presentations at international conferences. Results will improve identification of CRDs, addressing a significant gap in current PHC settings.

NCT07050823/NCT07093021/NCT07134855.

Health cadres, who assist midwives in supporting pregnant women in community settings, need to enhance their competencies in identifying risk factors and referring high-risk pregnant women to midwives for further care. Since the capabilities of these health cadres are influenced by maternal complications, an educational programme was implemented to strengthen their skills. Therefore, this study aimed to evaluate the competency of health cadres by providing a researcher-developed educational programme.

An open-label, cluster non-randomised controlled trial.

Health cadres with at least 1 year of work experience were recruited at six public health centres (PHCs) in Banjarnegara Regency, Indonesia.

Six PHCs were selected and allocated into intervention group (IG=3 PHCs) and control group (CG=3 PHCs) groups. A total of 133 female health cadres were enrolled across the selected PHCs. At each PHC, a systematic random sampling method was used to select the participants. The researchers and health professionals provided a 3-week period of theoretical and scenario-based simulations to the IG, while the CG received no education.

Researcher-developed questionnaires and checklists were used to assess the knowledge, skills (health assessment, communication, attitude) and confidence. The primary endpoint was competency, a total score of knowledge and skills. The outcome domains were compared between the two groups, and a linear mixed-effect model was used to account for cluster-level variation.

A total of 130 (97.7%) completed the study (IG:64, CG:66). The competency score showed significant improvement at endline (CG=49.5 and IG=52.5; p=0.002). The median scores for health assessment skills (CG=12 vs IG=14; p

Education effectively increased the competency of health cadres. A well-structured education programme is necessary for health cadres to improve and maintain their competencies in monitoring high-risk pregnant women.

NCT06134518.

To investigate treatment preferences of Japanese patients with locally advanced or metastatic urothelial carcinoma (la/mUC).

A discrete-choice experiment survey methodology was used to elicit patient preferences for attributes of la/mUC treatment, including adverse events (nausea/vomiting, neuropathy, alopecia and maculopapular rash), hospital stay requirements for treatment administration and overall survival. A multinomial logistic regression model was used to estimate treatment preferences. Coefficients of the model were then used to calculate the relative importance of each treatment attribute.

Participants were recruited through healthcare facilities with urology departments across Japan.

The study included 109 patients (72.5% male; mean (SD) age, 71.3 (8.9) years). Patients preferred treatments that minimised adverse events that could affect their daily activities, had a more favourable survival profile and did not require hospital stays for administration. Neuropathy emerged as the most important attribute to patients when making treatment decisions (relative attribute importance (RAI), 27.7%), followed by nausea/vomiting (RAI, 27.3%), maculopapular rash (RAI, 16.5%), hospital stay requirements (RAI, 12.1%), alopecia (RAI, 8.2%) and overall survival (RAI, 8.1%). Findings were similar across various subgroup analyses, though patients who were chemotherapy-experienced prioritised avoidance of neuropathy and nausea/vomiting more highly than those who were chemotherapy-naïve.

In this study, Japanese patients with la/mUC were more concerned about reduced quality of life due to adverse events than extending survival by 6 months. Patients, clinicians and other members of the care team need to communicate frequently and candidly about a patient’s well-being.

We conducted a pilot randomised controlled trial (the PHaCT study), including a process evaluation to assess the acceptability of a housing-led Critical Time Intervention (CTI) for prison leavers and the use of a trial design. This paper presents the process evaluation findings.

To explore the acceptability of both the intervention and the trial design to participants and those delivering the intervention, and to assess whether the intervention was delivered with fidelity.

A process evaluation following Medical Research Council guidelines. Data collection included semi-structured interviews with participants and CTI caseworkers and observations of intervention delivery. A thematic analysis of interviews and observations was conducted to understand the intervention’s implementation and contextual factors as well as the trial process acceptability.

Participants for the pilot trial were recruited from three prisons in England and Wales where the intervention was being delivered.

While 28 out of 34 trial participants consented to interviews, only one was completed. Seven caseworkers were interviewed.

A housing-led CTI to support people leaving prison at risk of homelessness, involving phased, time-limited support from caseworkers, starting prerelease and continuing postrelease, to help secure stable housing and build independence, without directly providing housing.

The intervention’s acceptability was primarily reflected through the positive feedback and success stories shared by CTI caseworkers, as well as observational data indicating high acceptance among service users. The trial design’s acceptability was challenged by concerns about randomisation and equipoise, with staff viewing randomisation as unethical due to limited support for vulnerable populations. The fidelity to the CTI intervention housing-led approach was adhered to as best as possible; stable housing was prioritised for service users before addressing other needs. Despite these efforts, both sites encountered significant challenges due to limited housing availability and complex systems for securing social housing, particularly for single men leaving prison.

This wider study faced significant challenges which impacted the process evaluation. Despite these issues, the evaluation provides important insights into the challenges of conducting trials on interventions for people leaving prison. The challenges experienced should inform future study designs with similar populations and in similar settings.

ISRCTN46969988.

To determine whether a full-scale randomised control trial (RCT) assessing the efficacy and cost-effectiveness of a housing led Critical Time Intervention (CTI) is feasible and acceptable.

Pilot parallel two-arm individual level RCT, including process evaluation and embedded exploratory health economic evaluation.

Four prisons for men across England and Wales, UK.

Men leaving prison at risk of homelessness and intervention delivery staff.

CTI has four components: (1) pre-engagement phase: assessing the needs of the client and implementing a plan pre-discharge; (2) transition to community: forming relationships and goal setting; (3) try out: encouraging problem-solving and managing practical issues and (4) transfer of care: developing long-term goals and transferring responsibilities to community providers.

Progression criteria: recruitment, retention, acceptability of the processes (CTI and trial method) and fidelity of intervention delivery. We also assessed the completeness of primary, secondary and exploratory outcome measures and estimated intervention costs.

The recruitment progression criterion was met, with 92% (34/37) of approached individuals consenting to participate (target: 50%). However, the overall recruitment target of 80 was not achieved, and retention was low, only 18% (6/34) provided follow-up data, well below the 60% threshold. Retention was hindered by systemic challenges, including changes to prison release policies and reduced probation support. While the CTI model was acceptable to staff and service users, the trial design, particularly randomisation, was not. Intervention fidelity met the progression criteria. Baseline data collection for health economics and resource use was feasible, and intervention costs were estimated.

This pilot trial identified significant challenges to conducting a full-scale RCT of CTI in this context, particularly around retention, trial acceptability and systemic instability. While CTI remains a promising model, a traditional RCT design may not be viable in this setting without substantial structural and ethical adaptations.

ISRCTN46969988.

To explore the experiences of different stakeholders on the balance of package training and deployment of highly skilled Human Resources for Health for specialised services in Tanzania.

An exploratory qualitative case study was used as part of a larger tracer study conducted by Muhimbili University of Health and Allied Sciences (MUHAS) for its postgraduate programmes being a requirement for quality assurance. Semi-structured interview guides were used for in-depth interviews (IDIs) and focus group discussions (FGDs). Qualitative content analysis was adopted to analyse the data.

The trace study was carried out in all seven geopolitical zones of the Tanzania mainland and Unguja in Zanzibar.

We conducted 14 FGDs and 301 IDIs. Participants included alumni, immediate supervisors at employment sites, MUHAS faculty, continuing students at MUHAS and management of professional councils in Tanzania.

Key findings revealed variations in demands and recognition within the scheme of services, even after registration by professional councils. Five main themes emerged from the qualitative interviews: Package training to improve service provision, Unprofessional collegial relationships or issues related to professionalism within interdisciplinary teams, Silence of scheme services on super specialisation in the medical cadre, Silence of scheme services on specialisation in the nursing cadre, Integrated scheme of services for specialties in pharmacy.

The findings highlight the demand for specialised training, challenges with professionalism and inconsistencies in the recognition and remuneration of specialists across medical, nursing and pharmacy cadres within existing service schemes. There is a need for harmonisation between specialisation/super specialisation and the scheme of services. This harmonisation is crucial to ensure the provision of quality healthcare services. Furthermore, harmonisation requires multistakeholder engagement to realise universal health coverage strategies.

The intestinal microbiota of people with Parkinson’s disease (PwP) differs significantly from that of healthy individuals. Given that altered microbiota may play a role in the pathogenesis of Parkinson’s disease, faecal microbiota transplantation (FMT) has been proposed as a potential therapeutic approach. However, the efficacy of FMT in improving motor symptoms in PwP has been inconclusive in some pilot randomised controlled trials (RCT). Previous RCTs on PwP employed simple FMT, but our modified approach—pretreatment with antibiotics before FMT (A-FMT)—has been shown to improve the engraftment rate of given species and the beneficial effects of FMT. This study aims to evaluate the efficacy and safety of A-FMT for PwP, particularly in those with motor fluctuations.

This study is a randomised, double-blind, placebo-controlled, parallel-group study with an 8-week observation period following a single A-FMT. Thirty clinically established PwP with prominent motor fluctuation episodes will be randomised 1:1 to FMT or placebo. Participants in both groups will receive antibiotic treatment prior to colonoscopy for FMT or placebo treatment. Primary and secondary endpoints will include subjective and objective evaluations of motor and non-motor symptoms and will be evaluated before and after antibiotic treatment and at 4 and 8 weeks after the procedure. Exploratory endpoints will include blood and faecal sample analyses, advanced brain MRI and pharmacokinetic assessment of levodopa concentrations during a levodopa challenge test.

This study has been approved by the ethical committee of Juntendo University in August 2024 (J24-005) and will be conducted in accordance with the Declaration of Helsinki, the Japan Ministry of Health, Labour and Welfare Clinical Trials Act and related laws and regulations. All patient data will be anonymised to protect privacy and used solely for study purposes. Results will be published in academic journals and presented at conferences.

jRCTs031240344.

Preoperative biliary drainage (PBD) is often required for patients with pancreatic cancer accompanied by biliary obstruction to ensure the safe administration of neoadjuvant chemotherapy or to manage cholangitis and jaundice. Although endoscopic retrograde cholangiopancreatography (ERCP) is the standard approach for PBD, it carries a significant risk of post-ERCP pancreatitis. Endoscopic ultrasound-guided biliary drainage (EUS-BD), particularly via hepaticogastrostomy (EUS-HGS), offers a promising alternative that avoids papillary manipulation. However, the clinical utility of EUS-BD as primary drainage for PBD remains unclear due to a lack of prospective studies. This multicentre prospective trial aims to evaluate the safety and efficacy of EUS-HGS as primary drainage for PBD in patients with resectable or borderline resectable pancreatic cancer.

This multicentre prospective study involves seven institutions in Japan. Eligible patients will undergo EUS-HGS using a 7Fr plastic stent. The primary endpoint is clinical success, defined by improvements in bilirubin or liver enzyme levels within 14 days postprocedure. Secondary endpoints include technical success rate, adverse event incidence, stent patency and surgical outcomes. A total of 30 patients will be enrolled, considering an expected clinical success rate of 90% and a 10% dropout allowance.

This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2024-084). The results of this study will be reported at an international conference and published in an international peer-reviewed journal.

UMIN ID: 000055173.

Accidental hypothermia (AH) can occur in mild-to-severe cases; however, its management is crucial in severe cases as it can cause ventricular fibrillation and lead to death. Among various rewarming therapies for AH, endovascular catheter rewarming has been the focus of recent studies as a minimally invasive alternative to invasive internal rewarming, such as extracorporeal membrane oxygenation (ECMO). However, no study has demonstrated the efficacy and safety of endovascular catheter rewarming therapy. This study aimed to validate the efficacy and safety of endovascular catheter rewarming for patients with AH.

The intensive care with endovascular catheter rewarming in accidental severe hypothermia (ICE-CRASH II) study is a multicentre, randomised study of patients with AH. This study will include patients with AH (age ≥65 years, core temperature

This study was approved by the Hokkaido University Certified Review Board (approval number: 024-00013). Written informed consent will be obtained from all the participants or their legally acceptable representatives. The results will be disseminated through publications and presentations.

Japan Registry of Clinical Trials (jRCT1012240051).

To map, summarise and analyse the methodologies of corneal nerve fibre imaging in studies using in vivo confocal microscopy (IVCM) in diabetes and assess the potential for standardising methods and reporting.

A scoping review was conducted using five databases, MEDLINE, Embase, Cochrane, Web of Science and Scopus, with search terms related to IVCM, diabetes and corneal nerves. Two researchers independently screened the studies for eligibility. Relevant data were extracted and systematically analysed.

Out of 1533 screened articles, 195 met the inclusion criteria. Spanning from 2000 to 2024, the studies showed high variability in image acquisition, image processing, image analysis and reporting detail. Most studies used laser scanning confocal microscopy, examining the central cornea in both eyes in patients with type 2 diabetes, manually selecting 3–6 images from each eye, and using ACCMetrics and CCMetrics for quantifying corneal nerve fibre length in mm/mm². Many studies lacked sufficient methodological details for reproducibility.

IVCM studies of corneal nerve fibres in diabetes show substantial methodological heterogeneity and inconsistent reporting, limiting reproducibility. We propose a guideline to support standardisation and improve the reliability of future research.

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).

Presenteeism, defined as reduced work efficiency due to health issues despite attending work, accounts for a substantial proportion of labour productivity loss. Although pain significantly impacts presenteeism, the relationship between pain and presenteeism remains poorly understood due to the multifaceted nature of pain, encompassing psychosocial factors and daily functioning. This study aimed to identify which of these factors are significantly associated with presenteeism among employees.

Cross-sectional study using self-administered questionnaires and generalised additive model analysis.

Multiple workplaces (including a university and hospitals) in Japan.

Employed individuals (n=212, age range: 20–65 years; 59 males and 153 females) participated. They were recruited through workplace bulletin boards, email announcements and direct invitations. Participants with and without chronic pain were included.

Participants completed self-report measures, including the Health and Work Performance Questionnaire (HPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Pain Catastrophising Scale (PCS), Beck Depression Inventory-second edition (BDI-II), State-Trait Anxiety Inventory (STAI) and WHO Disability Assessment Schedule 2.0 (WHODAS 2.0).

The results indicated that absolute HPQ was significantly associated with BDI-II scores (F=4.51, p=0.035). On the other hand, relative HPQ was influenced by SF-MPQ (F=3.76, p=0.005), PCS (F=4.16, p=0.014), STAI (F=5.62, p=0.019) and limited daily activities (F=13.25, p=0.00035).

These findings suggest that presenteeism is multifactorial, with pain, psychosocial factors and daily functioning playing critical roles. Moreover, the impact of depression on presenteeism differs from that of pain and anxiety. Therefore, tailored intervention approaches may be required for each factor, ultimately improving workplace productivity.

This study was preregistered at UMIN-CTR (UMIN000054797).

Primary care nurses (PCNs) are the second largest workforce in primary care and play a critical role in facilitating access to coordinated care and reducing health disparities. There is renewed interest in team-based primary care as a solution for health workforce challenges. Some team models enable PCNs (ie, nurse practitioners, registered nurses, licensed/registered practical nurses) to leverage one another’s expertise to work to optimal scope; the extent to which this happens depends on multiple context-dependent factors. We will conduct an umbrella review to synthesise and compare international knowledge syntheses focused on scope of practice enactment (ie., roles and activities) of PCNs in primary care.

We will conduct the umbrella review according to the Joanna Briggs Institute methodology, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines, and using the Nursing Care Organization Framework as guidance. We will search a wide range of scientific electronic databases and grey literature sources, and consider articles published in English and French by the Organization for Economic Cooperation and Development and designated key partner countries for inclusion, with no publication date limits. Two independent reviewers will screen titles, abstracts and full-text articles, and any disagreements will be resolved through discussion or by a third reviewer. We will use the Risk of Bias Assessment Tool for Systematic Reviews to assess the quality and risk of bias in the included systematic and scoping reviews.

Results will be presented in a PRISMA Scoping Review flow diagram. We will synthesise data from included studies in a detailed literature review table and develop visual aids to communicate the shared and unique roles and activities of PCN scope of practice. We will disseminate the results of the review through peer-reviewed publications and conferences related to this field. Ethics approval is not required.

Dyspnoea affects 10% of the general population, and 12% of hospitalised patients report experiencing dyspnoea at rest. It is a common and distressing symptom experienced by people living with chronic obstructive pulmonary disease (COPD). Neuromodulation, which uses electrical stimulation to modulate neural pathways, is a validated clinical procedure offering a potential therapeutic approach. We speculate that non-invasive transcutaneous vagus nerve stimulation (tVNS) and trigeminal transcutaneous electric nerve stimulation (TENS) could improve dyspnoea management by targeting relevant neural circuits.

We will conduct a feasibility cross-over trial in people with severe COPD and significant exertional dyspnoea referred for pulmonary rehabilitation. Patients will be recruited following the prerehabilitation assessment visit comprising a clinical evaluation and a maximal cardiopulmonary exercise testing on ergocycle. Subsequently, two study visits will be conducted within 2 weeks apart from each other. Eight participants will perform a submaximal constant work rate at 80% workload of the VO₂ max, either with cervical tVNS (n=4) or trigeminal TENS (n=4). In a cross-over design, both patient groups will undergo sham and active treatment of the neuromodulation technique in a randomly assigned order. The main outcome will be feasibility, assessed by the percentage of patients who attend all visits and complete all tests. Secondary outcomes include other feasibility endpoints, the acceptability and suitability of the interventions (including an evaluation of sham as an exploratory outcome), and the incidence of adverse or undesirable events related to the procedures. Exploratory outcomes include changes in dyspnoea symptoms, measured using standardised questionnaires, such as Borg scale and the Visual Analogue Scale.

The protocol is approved by the institutional research ethics committee of the Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l’Estrie—CHUS, Sherbrooke, Quebec, Canada (#2025-5604) and follows 2013 Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. Results will be communicated in international meetings and submitted to peer-reviewed journals with respect to the 2010 CONsolidated Standards Of Reporting Trials (CONSORT) statement for feasibility studies.

NCT06985628.