Prescription digital therapeutics (PDTx) represent an emerging frontier in healthcare, leveraging software-based solutions to treat or manage specific medical conditions. However, despite rising interest and encouraging evidence of clinical benefits, the policy landscape remains fragmented. Jurisdictions vary widely in their regulatory approaches, reimbursement pathways and processes for clinical integration, thus creating uncertainties for developers, payers and healthcare providers. This protocol outlines an eDelphi study to develop and validate a comprehensive policy maturity framework guiding systematic assessment of national or regional readiness for PDTx adoption.

We will conduct an e-Delphi study with up to three rounds to refine and validate a PDTx policy maturity framework. Experts will be recruited purposively from six stakeholder groups (regulators, healthcare providers, payers/health economists, developers, researchers and patient advocates), prioritising Europe while seeking variation across health system types and levels of economic development; a small number of non-European experts may be invited to broaden perspectives. An optional pilot round will gather initial feedback on the prototype framework, followed by iterative rounds to assess and revise domains, scoring criteria and maturity thresholds. A 5-point Likert scale (from ‘strongly disagree’ to ‘strongly agree’) will collect quantitative data, while open-text prompts will capture qualitative insights. Consensus will be defined as ≥70% agreement and/or an IQR ≤1 for critical items. Quantitative summaries and thematic analysis will guide iterative revisions of the model. This Delphi protocol aims to produce a consensus-driven framework that captures the essential elements of PDTx policy development and implementation. If validated, the framework can serve as a reference for policymakers, industry leaders, healthcare providers and researchers seeking to benchmark or advance the adoption of PDTx within health systems.

Ethical approval for this study was obtained from the Ethics Committee of the Faculty of Medicine of the University of Porto (reference: 320/CEFMUP/2025). Panellists will provide electronic informed consent, and data will be kept confidential. The finalised framework will be disseminated via peer-reviewed publications, conference presentations and policy briefs targeting stakeholders involved in digital health governance.

People with serious mental illness (SMI) can experience significant physical health challenges. The Health Champions intervention was developed to support their physical health through using trained volunteers. However, volunteer and patient perspectives on the impact and implementation of this intervention have yet to be understood.

To compare the views of patients and volunteers on the Health Champions intervention.

A qualitative thematic analysis was conducted on interviews with 29 study participants. Interviews were carried out either face-to-face, via Microsoft Teams, or by telephone and included 12 patients (6 men and 6 women) and 17 volunteers (the Health Champions) (5 men and 12 women).

Four overarching themes were identified, highlighting both similarities and differences between stakeholders’ perspectives: (1) supporting goal setting; (2) impact on positive lifestyle; (3) experiences and perception of the programme and (4) navigating challenges during the programme. Both groups found the programme to be largely successful, by motivating patients to work towards their physical health goals and facilitating successful matching of patients with volunteers. Volunteers and patients valued good communication with the research team. Though both groups shared some views on the challenges with scheduling and a lack of face-to-face contact during the COVID-19 pandemic, their perceptions on how patients incorporated their health changes during and after the programme, as well as other administrative concerns such as views on the efficacy of journaling and breakdown of roles, differed.

The Health Champions intervention was perceived as useful to improve the physical health of patients with SMI. Differences in the views between the two stakeholders may result from their distinct experiences and expectations. Future volunteering programmes should further support the diverse physical health needs of patients with SMI.

Yoga has been shown to improve pain and function compared with no exercise in people with chronic low back pain (LBP), but treatment effects are small. Given that yoga is a mind–body intervention that addresses physical as well as psychological factors, it may be more effective for patients with chronic LBP who are at high risk of poor prognosis. The study aims to investigate the efficacy of a 12-week yoga programme combined with education in reducing pain and disability for individuals with chronic LBP at high risk of poor prognosis at short (12 weeks) and intermediate (24 weeks) terms, compared with a control group receiving education only.

A randomised controlled trial will include 110 adults with chronic non-specific LBP reporting an average pain intensity of 3 points or more on a 0–10 scale over the past week and classified as high risk of poor prognosis (ie, scoring 50 points or above) on the Orebro Musculoskeletal Pain Questionnaire short-form. Participants in the control group will receive an educational booklet and attend three face-to-face lectures over a 3-month period. In the intervention group, in addition to the booklet and lectures, participants will attend group yoga sessions twice a week for 12 weeks, totalling 24 yoga sessions. The primary outcome is disability assessed at 12 weeks, measured using the Roland-Morris Disability Questionnaire.

The study was approved by the Human Research Ethics Committee of Universidade Federal de Minas Gerais (Protocol number CAAE: 57028022.0.0000.5149). Findings will be disseminated to trial participants, clinicians and the broader public and scientific community.

NCT05953155.

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.

Gram negative bloodstream infections (GN BSI) are a leading cause of mortality worldwide, and antibiotic treatment approaches remain understudied. BALANCE+ is a perpetual Bayesian adaptive platform trial to test multiple treatment questions for hospitalised patients with GN BSI. The vanguard phase objective was to test the feasibility of the main trial.

Adaptive platform trial with five initial domains of investigation, each with open label 1:1 randomisation.

Ten hospitals across four Canadian provinces.

Individuals admitted to hospital with blood cultures yielding Gram negative bacteria.

The five initial domains of investigation included: antibiotic de-escalation versus no de-escalation; oral transition to beta-lactam versus non-beta-lactam treatment; routine versus no routine follow-up blood cultures (FUBCs); central vascular catheter replacement versus retention; and, ceftriaxone versus carbapenem treatment for low risk AmpC organisms.

Domain-specific recruitment rates and protocol adherence.

During the vanguard phase, 719 patients were screened, of whom 563 (78.3%) were eligible, with 179 (31.8%) enrolled into the platform. The platform recruitment rate was 1.37 patients/site-week. Recruitment varied by domain: routine versus no FUBC domain 1.23 patients/site-week; oral beta-lactam versus non-beta-lactam domain 0.48; de-escalation versus no de-escalation domain 0.28; low risk AmpC domain 0.02; catheter replacement versus retention domain 0.01. Domain specific protocol adherence rates were 145/158 (91.8%) for routine versus no routine FUBC, 53/60 (88.3%) for oral beta-lactam versus non-beta-lactam, 26/33 (78.8%) for de-escalation versus no de-escalation, 3/3 (100%) for low risk AmpC, and 0/1 (0%) for line replacement versus retention. There was complete ascertainment of all study outcomes in hospital 170/170 (100%) and near complete ascertainment at 90 days 162/170 (95.3%).

The vanguard phase demonstrated overall trial feasibility by recruitment rate and protocol adherence, with differences across interventions, leading to a transition to the main BALANCE+ platform trial with minimal protocol modifications.

NCT05893147.

Depression and depressive symptoms are common in the elderly population and contribute to a lower quality of life. One change that is common in depression is the disruption of circadian cycles, which are regulated by melatonin and other neurotransmitters. Oral melatonin and melatonin agonists are well tolerated, being the main clinical indication of insomnia. A melatonin agonist is approved as an antidepressant. Thus, the objective of the systematic review will be to provide an up-to-date synthesis of the findings of randomised controlled trials that used melatonin or melatonin agonists as a therapeutic intervention in elderly people with depression.

This systematic review protocol was registered with PROSPERO under the number CRD42023391092. We will conduct a systematic review and possible meta-analysis of the efficacy of melatonin and melatonin agonists in the treatment of depression. Comparators will include placebo and active treatments (eg, antidepressants). We will search international electronic databases, including the Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials), EMBASE, PUBMED/MEDLINE and SciELO for published randomised control trial studies, and ongoing work and trials in progress by searching key internet-based relevant databases from inception to April 2025. There will be no restrictions on the language or geography of publication. The Cochrane’s risk of bias tool for randomised trials (RoB2) will be used to appraise the risk of bias, and GRADE tools will be used to evaluate the overall quality of the included studies. A descriptive summary with data tables will be constructed, and if adequate, we will perform a meta-analysis. A random-effects model will be used when substantial heterogeneity is present, otherwise, a fixed-effects model will be considered (I²). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist will be followed for reporting.

Since this systematic review will be based only on published and retrievable literature, no ethics approval will be required. A multidisciplinary team has been assembled for this systematic review and will participate in relevant dissemination activities, namely reports, publications and presentations.

CRD42023391092.

Acute hypoxaemic respiratory failure is a common reason for intensive care unit (ICU) admission. Non-invasive respiratory support strategies such as high-flow nasal oxygen (HFNO) and helmet non-invasive ventilation may reduce the need for invasive mechanical ventilation and death. The High-flow nasal Oxygen with or without alternating helmet Non-invasive ventilation for Oxygenation sUpport in acute Respiratory failure pilot trial is designed to compare helmet non-invasive ventilation combined with HFNO vs HFNO alone in patients with acute hypoxaemic respiratory failure and to determine the feasibility of a larger randomised controlled trial.

This is a pragmatic, open-label, multicentre randomised controlled pilot trial enrolling 200 critically ill adults with acute hypoxaemic respiratory failure across 12 Canadian ICUs. Participants are randomised 1 to 1 to receive either helmet non-invasive ventilation plus HFNO or HFNO alone for at least 48 hours. The primary aim is to assess feasibility metrics including recruitment rate, protocol adherence and fidelity to pre-specified intubation criteria. Secondary outcomes include rates of intubation, all-cause mortality, ventilator-free days, ICU length of stay and quality of life at 6 months. Primary and secondary outcomes will be analysed using Bayesian methods.

Ethics approval has been obtained at all participating centres. Findings will inform the feasibility and design of a future full-scale trial and be disseminated through peer review publications and conference presentations.

ClinicalTrials.gov Identifier: NCT05078034.

Eating disorders are complex mental health conditions characterised by pathological behaviours related to food intake, often accompanied by a chronic obsession with weight control. Their prevalence is increasing, with an earlier onset and greater severity among young people. Universal prevention, through multicomponent strategies that tackle modifiable risk factors, has emerged as a promising tool. This paper reports the study protocol designed to assess the effectiveness and cost-effectiveness of the PRETA (Prevención de los Trastornos de la Alimentación) programme in reducing the risk of eating disorders and related modifiable risk factors among preadolescents in the school setting.

The PRETA programme will be assessed by means of an open, community-based, multicentre, controlled trial using 1:1 matched-pairs cluster randomisation at the school level. Schools in Tenerife (Spain) will be assigned to the PRETA programme or a waitlist control group. Participants include 5th- or 6th-grade students (10–13 years old), their parents and teachers. The PRETA programme is a universal, school-based, multicomponent programme designed to reduce eating-disorder risk and modifiable risk factors. Its main component is an interactive online platform called e-PRETA, complemented by training sessions for families and teachers. e-PRETA includes nine 45-minute sessions addressing risk factors, such as dietary habits, beauty standards, media literacy, self-esteem, emotional regulation and social skills. A total of 1068 children from 12 schools will participate. The primary outcome will be the risk of developing eating disorders (Children’s Eating Attitudes Test-26 item version). Secondary outcome measures are body dissatisfaction (Adapted Contour Drawing Rating Scale), eating disorder traits (Eating Disorder Inventory-2), internalisation of appearance ideals (Sociocultural Attitudes Towards Appearance Questionnaire-4) and self-esteem (Rosenberg Self-Esteem Scale). Outcomes will be assessed at baseline and postintervention (3 months). Additional baseline covariates such as electronic device use, parental feeding attitudes, physical activity, sleep duration and screen time will also be collected. Programme effectiveness will be analysed using generalised mixed models. Cost-effectiveness will be assessed by comparing the incremental costs associated with the implementation of the PRETA programme with its estimated effectiveness.

Ethics approval has been obtained from the Ethics Committee for Research with Medicines at the University Hospital of the Canary Islands (CHUC_2021_78). Written informed consent will be obtained from the parents or legal guardians of all participants. Results will be disseminated through scientific publications and conferences.

NCT06792981.

Inhaled anaesthetics can be used in mechanically ventilated critically ill patients to provide sedation. This approach to sedation potentially improves patient and health system outcomes, but further supportive evidence is needed. The objective of the SAVE-ICU clinical trial is to compare the effectiveness of inhaled versus intravenous sedation in ventilated adults with acute hypoxaemic respiratory failure.

SAVE-ICU is a multicentre, open-label, pragmatic, randomised controlled trial conducted in 15 intensive care units (ICUs) in Canada and the USA. Eligible patients include mechanically ventilated and sedated adults with acute hypoxemic respiratory failure from COVID-19 or non-COVID causes with PaO₂/F_IO₂ ratio 12 hour). A hierarchy of outcomes was identified at the time of trial design, as the trial was launched during the COVID-19 pandemic when study drug shortages, staffing challenges and healthcare system pressures were prevalent and there was a requirement for rapid evidence generation and implementation on this topic. The primary outcome and highest in the hierarchy is hospital mortality (requiring 758 participants). Secondary and lower hierarchical outcomes are ventilator-free days at day 30 (200 patients), quality of life at 3 months (144 participants) and ICU-free days at day 30 (128 participants). Additional secondary outcomes include median daily oxygenation at day 3 (PaO₂/F_IO₂ ratio), need for adjunctive acute respiratory distress syndrome therapies (prone positioning, inhaled nitric oxide, paralysis with a neuromuscular blocking agent and extracorporeal membrane oxygenation) during ICU stay, days alive and free from delirium and coma at day 14, hospital-free days at day 60 and disability score at 3 months and 12 months after enrolment.

The protocol was approved by all hospital ethics committees and by Health Canada. Informed consent will be obtained from substitute decision makers or deferred consent (as permitted by site ethics board). Trial findings will be shared at the end of the study using peer-review publications, conference presentations and social media as part of the trial knowledge translation plan.

NCT04415060.

Intensive care units (ICUs) exposes both patients and families to an unfamiliar/stressful environment, featuring the urgency for enhanced end-of-life (EoL) care within ICUs.1 2 The emotional burden of EoL decisions can intensify the needs of bereaved families, leading to decreased quality of life,...

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) entails substantial morbidity and mortality, yet no epidemiologic evidence exists on its outcomes in Mexico. This study assessed national hospitalisations (2005–2022) and mortality (2000–2022) related to AAV using data from the General Board of Health Information.

Retrospective, population-based time-trend analysis on administrative health data.

Mexico’s national hospital discharge and mortality registries, covering 1 January 2000 through 31 December 2022.

All individuals aged ≥ 15 years with a primary or secondary International Classification of Diseases, 10th revision, diagnosis of AAV recorded during hospitalisation or on death certificates nationwide.

The study’s primary outcomes were the age-standardised hospitalisation and mortality rates for AAV (expressed per 100 000 population, overall and by sex), with temporal trends in both rates quantified using Joinpoint regression to calculate annual percent change (APC) and average APC (AAPC).

We identified 2804 hospitalisations and 599 deaths. Females accounted for 49.7% of hospitalisations, while males represented 48.7% of deaths. Although the overall age-standardised hospitalisation rate (ASHR) and mortality rate (ASMR) AAPCs were not statistically significant, relevant trends emerged. From 2010 to 2022, ASHR declined significantly (APC: –5.2%; 95% CI –9.7, –0.5; p=0.03), whereas mortality rates remained stable from 2000 to 2022 (AAPC: +3%; 95% CI –4.6, 11.3; p=0.45). Nevertheless, mortality increased among males (APC: +6.4%; 95% CI 0.9, 12.2; p=0.02) and individuals over 45 years (APC: +8.6%; 95% CI 1.7, 16.0; p=0.02) from 2008 onwards.

Overall, these findings indicate no major changes in national rates but reveal a decline in hospitalisations since 2010 and a rise in mortality for specific subgroups since 2008. Targeted interventions, particularly for older adults and men, appear warranted to address this evolving disease burden. Future research should explore underlying risk factors and evaluate tailored strategies to improve clinical outcomes in AAV across Mexico.

This study validates the previously tested Screening for Poverty And Related social determinants to improve Knowledge of and access to resources (‘SPARK Tool’) against comparison questions from well-established national surveys (Post Survey Questionnaire (PSQ)) to inform the development of a standardised tool to collect patients’ demographic and social needs data in healthcare.

Cross-sectional study.

Pan-Canadian study of participants from four Canadian provinces (SK, MB, ON and NL).

192 participants were interviewed concurrently, completing both the SPARK tool and PSQ survey.

Survey topics included demographics: language, immigration, race, disability, sex, gender identity, sexual orientation; and social needs: education, income, medication access, transportation, housing, social support and employment status. Concurrent validity was performed to assess agreement and correlation between SPARK and comparison questions at an individual level as well as within domain clusters. We report on Cohen’s kappa measure of inter-rater reliability, Pearson correlation coefficient and Cramer’s V to assess overall capture of needs in the SPARK and PSQ as well as within each domain. Agreement between the surveys was described using correct (true positive and true negative) and incorrect (false positive and false negative) classification.

There was a moderate correlation between SPARK and PSQ (0.44, p60), SPARK correctly classified 90.5% (n=176/191).

SPARK provides a brief 15 min screening tool for primary care clinics to capture social and access needs. SPARK was able to correctly classify most participants within each domain. Related ongoing research is needed to further validate SPARK in a large representative sample and explore primary care implementation strategies to support integration.

Fatigue is a common and debilitating symptom that is associated with an increased risk of mortality, dialysis initiation and hospitalisation among patients with chronic kidney disease (CKD). The aim of this study was to identify the characteristics, content and psychometric properties of patient-reported outcome measures (PROMs) used to measure fatigue in patients with CKD not requiring kidney replacement therapy (KRT).

Systematic review. The characteristics, dimensions of fatigue and psychometric properties of these measures were extracted and analysed.

We searched MEDLINE, Embase, PsycINFO and CINAHL from database inception to February 2023.

All studies that reported fatigue in patients with CKD stages 1–5 not receiving KRT.

We identified 97 studies (20 (21%) randomised trials, 2 (2%) non-randomised trials and 75 (77%) observational studies). 27 different measures were used to assess fatigue, of which three were author-developed measures. The 36-Item Short Form Health Survey (SF-36) and Kidney Disease Quality of Life – Short Form (KDQOL-SF) were the most frequently used measures (41 (42%) and 24 (25%) studies, respectively). Six (22%) measures were specific to fatigue (Chalder Fatigue Questionnaire, Functional Assessment of Chronic Illness Therapy – Fatigue Scale, Functional Assessment of Cancer Therapy-Fatigue, Fatigue Severity Scale, and author developed Chen & Ku 1998, and Hao et al 2021) while 21 (78%) included a fatigue subscale or item within a broader construct for example, quality of life. Various content domains assessed included tiredness, ability to think clearly, level of energy, muscle weakness, ability to concentrate, verbal abilities, motivation, memory, negative emotions and life participation. Only two measures (Chronic Kidney Disease Symptom Index – Sri Lanka, Kidney Symptom Questionnaire) were developed specifically for CKD, but they were not specific to fatigue. Six measures (Chronic Kidney Disease Symptom Index – Sri Lanka, Functional Assessment of Cancer Therapy – Anemia, Revised Illness Perception Questionnaire, Kidney Symptom Questionnaire, Short Form 6 Dimension and 36-Item Short Form Health Survey) had been validated in patients with CKD not requiring KRT.

PROMs used to assess fatigue in patients with CKD vary in content and few were specific to fatigue in patients with CKD not requiring KRT. Data to support the psychometric robustness of PROMs for fatigue in CKD were sparse. A validated and content-relevant measure to assess fatigue in patients with CKD is needed.