High costs of screening and diagnostic tests remain a major barrier to timely tuberculosis (TB) identification in resource-limited settings. Evidence on the cost-effectiveness of scalable screening algorithms is limited. Start4All is a research project aimed at developing and evaluating algorithmic approaches to TB screening and diagnosis, with the goal of optimising technical and allocative efficiency when expanding diagnostic coverage to primary healthcare and community settings.

Five screening and diagnostic tests will be evaluated: a capillary blood-based assay (C-reactive protein (CRP)), sputum-based rapid molecular tests (PCR; individual and pooled Xpert MTB/RIF Ultra assay (Xpert Ultra, Cepheid®, California, USA)), a lateral-flow urine-based test for lipoarabinomannan (LF-LAM), and digital chest X-rays with artificial intelligence-based computer-aided detection (CXR-CAD). A microbiological reference standard of positive culture using the mycobacteria growth indicator tube will be used to confirm TB disease.

We will compare the cost and effectiveness of concurrent and sequential positive serial combinations (screening algorithms) of CRP, CXR-CAD, LF-LAM, individual and pooled Xpert Ultra. Diagnostic performance will be estimated using sensitivity, specificity, predictive values and proportions of positive results, with Bayesian inference used to derive these estimates. The analysis will include adults (15 years and older) only and will be stratified by HIV status and level of care, including facility and community-based case finding. Effectiveness will be assessed based on the number of people with TB detected. Cost analysis will be conducted from the provider perspective, incorporating commodity and implementation costs. A decision tree model will be developed to assess the cost per number of persons with confirmed TB detected across all countries. Probabilistic sensitivity analysis will be conducted to account for uncertainty in model parameters, incorporating willingness-to-pay and willingness-to-accept thresholds.

WHO ethical review committee approval ERC.0003921. Data will be available on reasonable request to the principal investigator of the consortium.

NCT05845112.

To evaluate the incremental diagnostic value and sub-phenotyping capability of Cardiovascular Magnetic Resonance (CMR) compared with Transthoracic Echocardiography (TTE) in patients with elevated left ventricular filling pressure (LVFP).

Prospective registry study. [Results from ClinicalTrials.gov ID NCT05114785]

A single NHS hospital in the UK.

The primary outcome was the rate of diagnostic discordance between TTE and CMR. Secondary outcomes included the characterisation of specific pathologies identified by CMR where TTE was normal, non-diagnostic or provided a non-specific diagnosis.

CMR demonstrated diagnostic discordance with TTE in 74% (n=194) of cases. In patients with a normal TTE (n=54), CMR identified heart failure with preserved ejection fraction (HFpEF) in 46% (n=25) and ischaemic heart disease (IHD) in 19% (n=10). For non-diagnostic TTE cases (n=15), CMR detected HFpEF in 53.3% (n=8) and IHD in 26.7% (n=4). Among those with non-specific left ventricular hypertrophy on TTE (n=47), CMR revealed HFpEF in 45% (n=21) and hypertrophic cardiomyopathy in 34% (n=16).

CMR markedly improves diagnostic precision and sub-phenotyping in patients with elevated LVFP, identifying key conditions like HFpEF, IHD and specific cardiomyopathies that TTE frequently misses. These findings highlight CMR’s critical role as a complementary imaging tool for refining diagnoses and informing management strategies in cardiovascular conditions.

This study explores the challenges experienced by Australian healthcare professionals (HCPs) in delivering type 2 diabetes care to people of culturally and linguistically diverse (CALD) backgrounds. We examined how sociocultural, linguistic and health systems factors influence their clinical practice.

A qualitative study employing semi-structured interviews was conducted from April to October 2024. Data were analysed using Braun and Clarke’s reflexive thematic analysis to identify patterns and themes in HCPs’ experiences, guided by a constructivist perspective.

The study was conducted in metropolitan Melbourne, Australia, across primary and tertiary healthcare settings.

A purposive sample of 11 Australian HCPs from diverse disciplines, including general practice, pharmacy, nursing, endocrinology, dietetics and podiatry, participated. All had provided type 2 diabetes care to people of CALD backgrounds within the previous 12 months. Participants included both male and female professionals, many from ethnically diverse backgrounds.

Three overarching themes were identified, reflecting HCPs’ perceived challenges to providing culturally responsive type 2 diabetes care to people of CALD backgrounds. These themes illustrated the multilevel challenges encountered by HCPs at the patient, organisational and provider levels, namely: (1) healthcare provision across diverse health literacy and cultural contexts, (2) navigating system gaps in multicultural clinical practice and (3) workforce preparedness gaps in culturally responsive care.

HCPs remain committed to providing culturally responsive type 2 diabetes care but continue to face constraints, including limited cross-cultural training and exposure, inadequate interpreter access, time pressures and insufficient culturally adapted resources. Effective care in multicultural settings requires recognising patients’ culturally shaped beliefs about health and illness and embedding cultural humility, reflexivity and competence within professional practice, essential steps towards advancing equitable type 2 diabetes care across Australia’s diverse communities.

Obesity is a prevalent multifactorial disease worldwide that has become a major public health concern. Excess adiposity poses a health risk because it is related to several chronic diseases, which impact the person’s quality of life and present a greater risk of mortality. This study presents a protocol to evaluate the effectiveness of the Energy2MOB programme (Improvement of Obesity) in reducing body weight (between 5%–10%) in adults with obesity with a multicomponent group intervention of food education and physical activity.

Randomised clinical trial with two groups (control and intervention) of 1 year, which includes people from the Berguedà health region between 18 and 65 years old with grade II overweight (body mass index (BMI) between 27–30 kg/m²) or obesity (BMI between 30–40 kg/m²). Accepting an alpha risk of 0.05 and a statistical power >0.8 in a bilateral contrast, 68 subjects in each group are needed to detect a difference equal to or >2.5 kg.

The protocol was approved by the Ethics Committee of the University Institute for Research in Primary Care (IDIAP Jordi Gol) with the CEIm code: 24/303-P. The IDIAPJGol CEIm complies with the standards of Good Clinical Practice and with the current legislation that regulates its operation. The protocol complies with the ethical principles of the Declaration of Helsinki and applicable data protection regulations. All participants will provide written informed consent before participating. The dissemination plan includes presenting the results at national and international scientific conferences, publication in peer-reviewed journals, and sharing a plain-language summary with all participants through their primary care centres. Key findings will also be shared with local health authorities and community health professionals to inform future interventions on obesity prevention and management.

NCT06988904.

A growing number of individuals born with congenital heart disease (CHD) are surviving well into adulthood, and a successful transition from paediatric to adult healthcare is essential for their long-term health. However, discontinuity in care is prevalent.1 Parents play an important role in the transition process and may impact transition-related outcomes,2 but their experiences and...

Monitoring physical rehabilitation is an essential component of patient recovery after knee arthroplasty. Monitoring can be remote, or clinic based. In India, unsupervised home-based physical rehabilitation is a common practice, but there is a lack of evidence to demonstrate the effectiveness of remote monitoring. Therefore, we developed and piloted a mobile application (TeleREhabilitation after knee ArThroplasty app) based on behaviour design thinking to support the recovery period. This trial aims to compare the effectiveness, acceptability, cost and safety of this app-supported home-based intervention against usual care using an open label, 1:1 individual randomised superiority trial at two tertiary care hospitals in India.

Consecutive adults undergoing partial or total, unilateral or bilateral knee arthroplasty who can use a smart phone will be invited to participate in this trial. Consenting individuals will be randomised to either an app-supported intervention or a usual home-based rehabilitation which typically consists of provision of oral or written instructions at discharge and follow-up check-up with the surgeon or physiotherapist at their discretion or as per individual need. We aim to recruit 300 individuals over a period of eighteen months. The primary objective is to compare patient-reported knee function between the two groups at 3 and 6 months postsurgery. Secondary objectives are to compare patient-reported outcomes (pain and activity), performance-based outcomes (lower limb strength and knee function), resource utilisation and quality of life. Fidelity of implementation, end-user experiences and challenges in implementing this intervention will be measured using both quantitative and qualitative methods. Quantitative data will be analysed in Stata, and group comparisons will be done using mixed effect linear regression. A mixed-methods approach will be used to analyse and interpret the process evaluation data. A modified intention-to-treat approach will be taken, which includes all those who were randomised irrespective of their adherence to trial protocol if they had at least one follow-up visit after enrolment.

The protocol has been approved by the ethics committees of the sponsor institute (The George Institute for Global Health) and the two clinical sites (All India Institute for Medical Sciences, Delhi & Indraprastha Apollo Hospitals, Delhi). The results will be disseminated via peer-reviewed publications, conference presentations and via plain language newsletters to the trial participants.

CTRI/2024/06/068838.

The WHO Surgical Safety Checklist (SSC) can improve patient outcomes through checks and enhancing the safety climate, provided the team engage. Patients are central to that team and may be awake during part or all of many procedures. Their greater inclusion in the SSC process could enhance its checking objectives by using patient knowledge of details relevant to proposed procedures, and its objective of improving culture by emphasising patient identity, seeing patients as individuals rather than items on a production line. We aimed to evaluate SSC use, including clinicians’ and patients’ perspectives, in cardiothoracic operating rooms (CTORs) and cardiac catheterisation laboratories (CCLs), and to identify opportunities to refine its use in these spaces.

We undertook a multimethod study based on positivism and interpretivism, with evaluation of SSC administration and interviews. We evaluated SSC administration during 20 Sign Ins, 20 Time Outs and 20 Sign Outs in CTORs and 20 Time Outs in CCLs (11 coronary angiography and 9 electrophysiology cases) using the WHO Behaviourally Anchored Rating Scale (WHOBARS, 1–7, where higher scores indicate better practice). We additionally interviewed 10 clinicians and 17 patients about their experiences and perceptions of safety and SSC use. We undertook thematic analysis of interview data.

CTORs and CCLs in an Auckland public hospital.

We observed 171 clinicians during 20 cases. We interviewed 10 clinicians (Pakeha/New Zealand/European n=6; male n=5; doctor n=5). We interviewed 17 patients (Pakeha/New Zealand/European n=12; male n=10; age range 45–81 years).

In CTORs, the SSC was used in full: median (IQR) WHOBARS score was 5.9 (5.2, 6.5). In CCLs, its use differed between electrophysiology and angiography CCLs: median (IQR) WHOBARS score was 4.50 (3.2, 5.6). In both CTORs and CCLs, high levels of carefulness and respect between team members were observed. Clinicians described the SSC as valuable and identified context-related reasons for variations in its use. Patients wanted to feel cared for and respected (including culturally). The SSC contributed positively to this. Clinicians expressed reservations about increasing patients’ involvement with the SSC. However, patients’ comments supported their increased engagement in the SSC process (including establishing their preferred names).

The SSC is used at Auckland City Hospital with some variation between services and with high levels of carefulness and respect. The SSC increased patients’ sense of being cared for. With modification (eg, by verifying their preferred name during the Sign In phase), the SSC could enhance patients’ perception of being seen as individuals, their cultural safety and the safety climate in operating and procedure rooms, and hence potentially improve patient outcomes. Our findings reinforce the value of regular evaluation and context-relevant modification of SSC for its effective use.

Rheumatological diseases represent a widespread heterogeneous group of disorders, united by chronic musculoskeletal inflammatory processes. Despite the increasing effectiveness of new therapies, the lack of adequate treatments for certain conditions and the occurrence of adverse drug reactions have led to the need for alternative strategies, including food supplements. These products are perceived by the patient as a valuable aid without adverse effects. However, adverse reactions to food supplements have been reported, although their incidence cannot be established due to the lack of consumption data. In this context, the IntegraRE project aims at collecting information on the use of food supplements in rheumatology, considering both physicians and patients.

A survey-based cross-sectional study has been designed into two consecutive phases: Phase 1 aims to investigate rheumatologists’ knowledge, attitudes and recommendations to patients regarding food supplements, while Phase 2 focuses on estimating patients’ intake of food supplements, including the specific products used, unit consumed and reasons for their consumption. Questionnaires will be collected from at least 287 rheumatologists and 2000 patients, geographically distributed in proportion to the Italian population. These will gather information on sociodemographic variables, lifestyle factors, knowledge, clinical practices and supplement consumption.

The study protocol has been approved by the Ethics Committee of the Italian National Institute of Health (approval no. AOO 0032395 on 24 July 2024). The results, which will be widely disseminated through conference presentations, peer-reviewed publications and dedicated project webpage, will provide an understanding of the use of food supplements in rheumatology and allow guidelines to be drawn up on their correct use in the clinical practice of rheumatological diseases. Overall, this survey will increase people’s awareness of the effects of food supplements and encourage their safe and conscious use.

To assess the validity of the International Classification of Diseases, 10th Revision (ICD-10) healthcare database diagnosis codes for lithium toxicity at hospital admission in Ontario, Canada.

Population-based retrospective validation study.

A total of 152 hospitals linked to a provincial laboratory database in Ontario, Canada, from 2007 to 2023.

Patients 50 years of age or older taking lithium with hospital-based serum lithium laboratory measurements during admission to the hospital (n=2804).

Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) comparing an ICD-10 diagnostic coding algorithm for lithium toxicity to a serum lithium concentration of 1.5 mmol/L or more. The codes used in the algorithm were T568, T435, Y495, X41 and X49. Serum lithium values and changes in the concentration of serum lithium from baseline levels in patients with and without a diagnosis code for lithium toxicity (code-positive and code-negative, respectively).

The sensitivity of the ICD-10 coding algorithm for identifying a serum lithium level≥1.5 mmol/L was 84% (95% CI 81% to 87%). The specificity and the NPV were over 88%, and the PPV was 63% (95% CI 60% to 66%). The median (IQR) serum lithium measurement in code-positive patients was 1.7 (1.2 to 2.2) mmol/L, and it was 0.6 (0.4 to 0.9) mmol/L in code-negative patients. The median (IQR) increase in serum lithium concentration compared with the most recent prehospital baseline values was 0.7 (0.2 to 1.3) mmol/L in code-positive patients and 0.0 (–0.2 to 0.2) mmol/L in code-negative patients.

In Ontario, the sensitivity of the ICD-10 coding algorithms was moderate for identifying a serum lithium level≥1.5 mmol/L at hospital admission. The presence or absence of the ICD-10 codes for lithium toxicity at hospital admission successfully differentiated two groups of patients with distinct serum lithium measurements.

Patients receiving haemodialysis are at very high risk of fragility fracture, yet there are no proven treatments for fracture prevention. We will advance a pilot study on the feasibility of a large, pragmatic, randomised controlled trial (RCT) of denosumab for fragility fracture prevention in haemodialysis.

PRevEnting FracturEs in REnal Disease-1 is a pragmatic, open-label, pilot study of an RCT of a denosumab care pathway embedded in routine care haemodialysis centres.

We will recruit at least 60 participants at high risk of fracture from at least 6 haemodialysis centres in Ontario, Canada. They must be aged 40 years or older, have access to provincial drug coverage, have appropriate baseline calcium and parathyroid hormone levels and be deemed suitable for denosumab by their kidney care provider. Participants will be randomised 1:1 to denosumab (with supports to mitigate hypocalcaemia) versus usual care using block randomisation by a central statistician (computer-generated sequence). Primary outcomes include recruitment feasibility and adherence. Secondary outcomes include safety (hypocalcaemia) and participant satisfaction with our protocol and processes. Study investigators and data analysts will be blind to treatment allocation.

We will present results descriptively. The trial was approved by Clinical Trials Ontario and local research ethics boards across study sites.

Primary and secondary outcomes will be published on trial completion.

This pilot will inform the feasibility of conducting a large-scale, efficiently run, pragmatic RCT to test whether a denosumab care pathway safely reduces the risk of fragility fracture in patients receiving haemodialysis. Results have the potential to transform fracture care in real-world patients with kidney and metabolic bone disease.

NCT05096195.

The National Family Health Survey-5 has reported an under-five mortality rate of 41.9 per 1000 live births in India. Pneumonia, one of the leading causes of under-five mortality, contributes substantially to this figure. The Indian government has made efforts through multiple national programmes, but pneumonia-specific mortality remains high. The Government of India revised their Childhood Pneumonia Management Guidelines in 2019 to improve under-five pneumonia prevention and management. This implementation study aims to achieve a high population-based coverage of pneumonia treatment for under 5 yearold children in the Palwal district of India.

This implementation study uses a quasi-experimental pre-post design and a mixed-methods approach, conducted in three phases: (i) formative research, (ii) model optimisation through iterative testing in a learning block and (iii) scale-up and concurrent evaluation. The study is set in Palwal district, Haryana, and the primary catchment/study area will be the Health and Wellness Centres, the most accessible public health facilities for the community. Approximately 4167 households will be surveyed to capture ~2400 under-five children, among whom about 120 pneumonia cases (based on an estimated 5% prevalence) will be included in the analysis of treatment coverage and outcomes. Quantitative data will be analysed using descriptive statistics and generalised linear models, while qualitative data from focus group discussions and in-depth interviews will be thematically analysed using NVivo software.

Ethical approval was granted by the ethical committees of the Society for Applied Studies (ERC/IR Pneumonia/2021), the Regional Ethics Committee of Western Norway (2022/531608) and the WHO(ERC.0003652). Additionally, this study has obtained the Government of Haryana state (Memo no. HSHRC/2022/505) and Health Ministry steering committee (approval date: 19 Dec 2022, proposal id 2022–17596) approvals. Informed consent will be obtained from all participants, including caregivers and healthcare workers, prior to data collection. Dissemination meetings in the study country will share results with stakeholders, including Ministry of Health officials, health managers, families of under-five children, community leaders and academia, to discuss national health programme implications. Results will also be shared regionally and globally, with publications and presentations encouraged in national and international forums.

Clinical Trials Registry – India, CTRI/2021/03/031622.