In 2022, the WHO conditionally recommended the use of treatment decision algorithms (TDAs) for treatment decision-making in children

Within the Decide-TB project (PACT ID: PACTR202407866544155, 23 July 2024), we aim to generate an individual-participant dataset (IPD) from prospective TB diagnostic accuracy cohorts (RaPaed-TB, UMOYA and two cohorts from TB-Speed). Using the IPD, we aim to: (1) assess the diagnostic accuracy of published TDAs using a set of consensus case definitions produced by the National Institute of Health as reference standard (confirmed and unconfirmed vs unlikely TB); (2) evaluate the added value of novel tools (including biomarkers and artificial intelligence-interpreted radiology) in the existing TDAs; (3) generate an artificial population, modelling the target population of children eligible for WHO-endorsed TDAs presenting at primary and secondary healthcare levels and assess the diagnostic accuracy of published TDAs and (4) identify clinical predictors of radiological disease severity in children from the study population of children with presumptive TB.

This study will externally validate the first data-driven WHO TDAs in a large, well-characterised and diverse paediatric IPD derived from four large paediatric cohorts of children investigated for TB. The study has received ethical clearance for sharing secondary deidentified data from the ethics committees of the parent studies (RaPaed-TB, UMOYA and TB Speed) and as the aims of this study were part of the parent studies’ protocols, a separate approval was not necessary. Study findings will be published in peer-reviewed journals and disseminated at local, regional and international scientific meetings and conferences. This database will serve as a catalyst for the assessment of the inclusion of novel tools and the generation of an artificial population to simulate the impact of novel diagnostic pathways for TB in children at lower levels of healthcare. TDAs have the potential to close the diagnostic gap in childhood TB. Further finetuning of the currently available algorithms will facilitate this and improve access to care.

Ages of attainment for early gross motor milestones have been widely studied, but definitions and measurement methods have varied greatly. Since delays in motor milestones have been used extensively as one of the earliest indicators of atypical development, it is imperative to establish a universal understanding of the methods and results reported on motor milestones in typically developing children. Therefore, the primary aim of this scoping review is to provide an overview of recent studies reporting ages of onset for independent sitting and walking in typically developing children worldwide; this will be achieved by summarising how these milestones have been operationalised and evaluated, the samples from whom these data have been drawn, and the reported ages of acquisition.

To meet inclusion criteria, articles must: be original research papers published in any language since 2003, contain a sample of typically developing children and report actual ages of onset for independent sitting and/or walking. To conduct this scoping review, the Joanna Briggs Institute methodological framework will be used. Search terms will include variations of the following concepts: acquisition of motor milestone (independent sitting and/or walking), age of onset, infancy. Six databases (CINAHL Plus, Embase, PsycNet: PsycINFO & PsycArticles, PubMed, Scopus, Web of Science: Core Collection) will be searched. Records from these databases will be screened for eligibility. Two people will independently review each record during title and abstract screening, and three people will independently screen full texts and extract data. Results will be displayed in tables, graphs and narrative summaries in the scoping review.

As the review will only include previously published data, ethics approval is not required. Findings will be shared at scientific conferences and in a peer-reviewed journal.

Nipah virus (NiV) is a bat-transmitted paramyxovirus causing recurrent, high-mortality outbreaks in South and South-East Asia. As a WHO priority pathogen, efforts are underway to develop therapies like monoclonal antibodies and small-molecule antivirals, which require evaluation in clinical trials. However, trial design is challenging due to limited understanding of NiV’s clinical characteristics. Given the rarity of NiV infections, strategies targeting improved outcomes for the broader acute encephalitis syndrome (AES) patient population, including those with NiV, are essential for advancing therapeutic research. To address these gaps, we designed the Bangladesh AES cohort study to characterise the patient population, clinical features, treatment practices, common aetiologies and outcomes in patients presenting with AES, including NiV infection, as a clinical characterisation study to inform the design of clinical trials for NiV and AES more broadly.

This prospective cohort study will be conducted in Bangladesh, a NiV endemic country with annual outbreaks. In collaboration with the ongoing NiV surveillance programme in Bangladesh, we aim to enrol up to 2000 patients of all ages presenting with AES at three tertiary care hospitals within the Nipah belt. Patients who provide informed consent to participate will be monitored throughout their hospital stay until 90 days post enrolment. Data will be systematically collected through interviews and medical record reviews at several time points: on the day of enrolment, day 3, day 7, the day of critical care admission (if applicable), discharge day and 90 days post enrollment. Additionally, a portion of the cerebrospinal fluid collected under the concurrent NiV surveillance protocol will be tested for an array of viral and bacterial pathogens responsible for encephalitis at the International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) laboratory.

The study received ethical approval from the Oxford Tropical Research Ethics Committee, University of Oxford, UK (OxTREC Ref: 576–23) and the institutional review board of icddr,b, Bangladesh (icddr,b protocol number: 24016). By characterising the AES patient population, this study will generate essential evidence on key clinical parameters, which will be pivotal in optimising the design of clinical trials for potential interventions aimed at improving outcomes in patients with AES, including those with NiV disease. Findings will be shared with participating hospitals, patients and relevant government stakeholders. Results will also be disseminated through conference presentations and peer-reviewed publications.

Not applicable (this is an observational study).

To compare the quality and time efficiency of physician-written summaries with customised large language model (LLM)-generated medical summaries integrated into the electronic health record (EHR) in a non-English clinical environment.

Cross-sectional non-inferiority validation study.

Tertiary academic hospital.

52 physicians from 8 specialties at a large Dutch academic hospital participated, either in writing summaries (n=42) or evaluating them (n=10).

Physician writers wrote summaries of 50 patient records. LLM-generated summaries were created for the same records using an EHR-integrated LLM. An independent, blinded panel of physician evaluators compared physician-written summaries to LLM-generated summaries.

Primary outcome measures were completeness, correctness and conciseness (on a 5-point Likert scale). Secondary outcomes were preference and trust, and time to generate either the physician-written or LLM-generated summary.

The completeness and correctness of LLM-generated summaries did not differ significantly from physician-written summaries. However, LLM summaries were less concise (3.0 vs 3.5, p=0.001). Overall evaluation scores were similar (3.4 vs 3.3, p=0.373), with 57% of evaluators preferring LLM-generated summaries. Trust in both summary types was comparable, and interobserver variability showed excellent reliability (intraclass correlation coefficient 0.975). Physicians took an average of 7 min per summary, while LLMs completed the same task in just 15.7 s.

LLM-generated summaries are comparable to physician-written summaries in completeness and correctness, although slightly less concise. With a clear time-saving benefit, LLMs could help reduce clinicians’ administrative burden without compromising summary quality.

The evidence for the optimal duration of psychotherapy for borderline personality disorder (BPD) is scarce. Two previous trials have compared different durations of psychotherapy. The first compared 6 months versus 12 months of dialectical behaviour therapy for BPD (the FASTER trial). The second compared 5 months versus 14 months of mentalisation-based therapy for BPD (the MBT-RCT trial). The primary objective of the present study will be to provide an individual patient data pooled analysis of two randomised clinical trials by combining the two short-term groups and the two long-term groups from the FASTER and MBT-RCT trials, thereby providing greater statistical power than the individual trials. Accordingly, we will evaluate the overall evidence on the effects of short-term versus long-term psychotherapy for BPD and investigate whether certain subgroups might benefit from short-term versus long-term psychotherapy.

An individual patient data pooled analysis of the FASTER trial and the MBT-RCT trial will be conducted. The primary outcome will be a composite of the proportion of participants with a suicide, a suicide attempt or a psychiatric hospitalisation. The secondary outcome will be the proportion of participants with self-harm. Exploratory outcomes will be BPD symptoms, symptom distress, level of functioning and quality of life. We will primarily assess outcomes at 15 months after randomisation for the FASTER trial and at 16 months after randomisation for the MBT-RCT trial. Predefined subgroups based on the design variables in the original trials will be tested for interaction with the intervention as follows: trial, sex (male compared with female), age (below or at 30 years compared with above 30 years) and baseline level of functioning (Global Assessment of Functioning baseline score at 0–49 compared with 50–100).

The statistical analyses will be performed on anonymised trial data that have already been approved by the respective ethical committees that originally assessed the included trials. The final analysis will be published in a peer-reviewed scientific journal and the results will be presented at national seminars and international conferences.

CRD42024612840.

Indigenous Mayan-Yucatecan communities in Mexico have a high prevalence of chronic non-communicable diseases (NCDs) such as diabetes, hypertension, obesity and rheumatic diseases (RMDs). According to the syndemic theory, these diseases combined with social, economic and cultural factors affect the quality of life. The aim of this protocol is to describe the methodological process to create, implement and evaluate a Syndemic-Based Care Model (SCM), using a Community Based-Participatory Research (CBPR) strategy in three Mayan-Yucatecan communities.

This is a convergent mixed-methods protocol. The quantitative component is a before-after study, and the qualitative component is an ethnographic study. The intervention will be a SCM co-constructed with Mayan communities based on their particular needs and aiming for reduction of the negative impact of NCD/RMD through a multidisciplinary approach. We will follow four phases of the CBPR: (1) situational analysis, through community censuses and semistructured interviews to understand the prevalence of NCDs and the syndemics in these communities; (2) co-construction of the elements of a SCM based on the health priorities identified by researchers, community members and healthcare workers; (3) implementation of this SCM and (4) evaluation of the SCM through (1) statistical analyses involving the construction of a syndemic index through stepwise logistic regression of the normalised and standardised key clinical, social and economic variables; interval and ratio variables will be normalised by their z-score and categorical variables will be one-hot encoded; similarity and social networks analysis with clustering to identify syndemic subpopulations; and cost-effectiveness and cost-utility analyses using Markov modelling and (2) narrative and thematic qualitative analysis of the SCM’s implementation and impact on community members’ health, function and quality of life.

Research ethics boards of participant institutions approved this research protocol. This project will be presented to municipal authorities, community meetings and community leaders for observation and acceptance. For people who wish to participate, informed consent will be provided written and verbally in Spanish or Mayan-Yucatecan according to the participant preferences, and it can be signed by either autograph or fingerprint. The results of this research will be disseminated to various groups: (a) local and regional authorities of the Mexican health system and municipal authorities; (b) the participating communities will be informed in an assembly of the results and (c) academic dissemination will be done through publications in public science journals and institutional press releases and will also be presented at national and international congresses or symposia.

This study aimed to assess the proportion of nutrition-related information-seeking behaviour and its associated factors among pregnant women attending antenatal care at public hospitals in Bahir Dar City, northwest Ethiopia, 2023.

A cross-sectional quantitative supplemented with qualitative study design was conducted from March to April 2023 among 406 pregnant women. Pre-tested structured interviewer-administered and semistructured open-ended questionnaires were used to collect quantitative and qualitative data, respectively. Data were collected using the Kobo toolbox, and SPSS V.25 was used for analysis. Descriptive statistics were used to describe study subjects, and multivariate logistic regression analysis was employed to investigate the associated factors. The strength of associations was described using the OR with the corresponding 95% CI.

The study included 406 pregnant mothers with a median age of 28 with an IQR of 8 and 212 (52.2%) from rural settings. Of the total respondents, 173 (42.6%; 95% CI 37.7 to 47.6) of pregnant mothers were nutrition-related information seekers. Educational status, residence, monthly income and nutrition information literacy were significantly associated with nutrition-related information-seeking behaviour.

The proportion of nutrition information seeking among pregnant mothers in Bahir Dar City public hospitals was low. Lower educational status, low nutrition information literacy level, being from a rural residence and low monthly income are significantly associated factors.

Awareness creation for pregnant mothers from rural areas and with low educational status and improving nutrition information literacy of pregnant mothers are important activities to improve their nutrition information-seeking behaviour.

Cervical cancer remains a significant global health concern and is the fourth most prevalent cancer among women. In South Africa, it is the leading cause of cancer-related deaths in women aged 15–44 years. The disease is typically preceded by persistent high-risk HPV infection, leading to cervical intraepithelial neoplasia and eventually cancer. Currently, in South Africa, management primarily involves excision, particularly through large loop excision of the transformation zone, which has associated risks and limitations. Thermal ablation is an alternative cost-effective treatment method, providing a straightforward approach to treatment, particularly advantageous in environments characterised by limited resources. The study aims to assess the efficacy, safety and patient experience of thermal ablation, providing valuable data for potential integration into South Africa’s cervical cancer prevention policies.

Randomised controlled trial in which 420 women living with HIV aged 30–60 years will be recruited from the Colposcopy Clinic at Tygerberg Hospital and will be followed up for a period of two years. The primary study endpoint is a test of cure that will be assessed by HPV genotyping, cervical cytology and histology at six month intervals. Other endpoints include the occurrence of adverse events.

The study protocol has been approved by the Health Research Ethics Committee of Stellenbosch University (Ethics Reference No: M20/11/035) and by the Western Cape Department of Health and Wellness via the National Health Research Database (WC_202109_016). All study procedures comply with the Declaration of Helsinki, South African Good Clinical Practice Guidelines and the Medical Research Council’s ethical guidelines. Trial results will be disseminated through peer-reviewed journals, national and international conference presentations and professional associations. A lay summary will be shared with the Community Advisory Board to guide community-level dissemination.

Pan African Clinical Trial Registry: PACTR202504820339039.

Cortical spreading depolarisation (SD) is a pathological wave of depolarisation in the cortex. SDs occur frequently after severe acute brain injury, and SDs in clusters can contribute to secondary brain damage in patients with severe acute brain injury through hypoperfusion and upregulation of cerebral metabolism in vulnerable brain tissue. Ketamine appears to inhibit SDs both in vitro and in patient series of severe acute brain injury. The KETA-BID trial aims to examine the efficacy and safety of S-ketamine for SDs in severe acute brain injury, as well as the feasibility of the trial design.

This randomised, blinded feasibility and pilot trial includes adults (≥ 18 years) undergoing a supratentorial craniotomy or craniectomy for severe acute brain injury (ie, traumatic brain injury, aneurysmal subarachnoid haemorrhage or spontaneous intracerebral haemorrhage). During surgery, an electrocorticography (ECoG) strip is placed adjacent to injured brain tissue. Patients are continuously monitored throughout their stay at the neurointensive care unit and the neurosurgical step-down unit. In the case of an SD, physiological optimisation of intracranial pressure, brain tissue oxygen tension (PbtO₂), core temperature and blood glucose is initiated. Participants developing SD clusters are randomised for continuous infusion with S-ketamine or matching placebo in a 1:1 allocation with full blinding of the treatment allocation. Infusion rates (ie, dose) and duration of trial medication are adjusted following a dosing algorithm according to SD occurrence. Surviving participants are followed until 6 months after the injury with recording of functional outcome. The primary outcome is occurrence of SDs per hour of monitoring after randomisation.

The Scientific Ethics Committee of the Capital Region of Denmark (H-21056972), the Danish Medicines Agency (EudraCT 2021-003716-12), as well as the Clinical Trials Information System (CTIS 2024-515315-22-00) approved this trial. This trial will provide insight into both SD and the clinical effects of ketamine following severe acute brain injury, presenting a potential new treatment for these patients. The findings will be submitted for publication in peer-reviewed publications.

NCT05095857.

Living with epilepsy, especially drug-resistant epilepsy (DRE), imposes several challenges for people diagnosed with the condition. These challenges include the physical and mental implications of epilepsy on both caregivers and patients with epilepsy. For the more than 120 000 individuals living with this neurological disorder in the Netherlands, along with their families, daily activities become hazardous, limited and costly, significantly affecting their health-related quality of life (HRQoL). As data on the burden of epilepsy in the Netherlands are lacking, studies attempting to capture the impact of epilepsy on individuals, caregivers and society are needed to enhance understanding and help address the burden of epileptic seizures.

The study is part of the AIM@EPILEPSY project. The project aims to develop a planning suite enabling cost-saving, minimally invasive treatment for epilepsy. By surveying 330 people with epilepsy and an anticipated sample of 150–200 informal caregivers across the Netherlands, using standardised questionnaires focusing on associated societal costs and the impact on HRQoL, this bottom-up, prevalence-based prospective study aims to understand the societal burden of DRE in the Netherlands. The data will be collected at 0, 3, 6 and 12 months of follow-up. The study results will describe the economic impact of epilepsy, focusing on cost-of-illness () and HRQoL (utilities) in the Netherlands.

The proposed study was approved by the Maastricht University Medical Ethics Review Committee (Approval reference: FHML-REC/2024/067/Amendment/2024_16). The result of the study is planned to be published in a peer-reviewed journal and presented at international and local scientific conferences.

Methadone and buprenorphine/naloxone are effective medications for people with opioid use disorder; however, interruptions in daily dosing are common and diminish the benefits of these medications. While clinical guidelines in most North American jurisdictions, including British Columbia (BC), recommend dose adjustment after treatment interruptions to varying levels of specificity, the evidence to support these recommendations is limited. We aim to estimate the comparative effectiveness of alternative dose adjustment strategies on subsequent overdose-related acute care visits and discontinuation of opioid agonist treatment in BC, Canada.

Using a linkage of nine health administrative databases, we propose a population-level retrospective cohort study of adults aged 18 years or older in BC who initiated methadone or buprenorphine/naloxone between 1 January 2010 and 31 December 2022. We will specify parallel hypothetical trials, known as target trials, for methadone interruptions of 1–3 days, 4 days and 5–14 days, and buprenorphine/naloxone interruptions of 1–5 days and 6–14 days. Following the index interruption, the primary outcomes are the time to overdose-related acute care visits and treatment discontinuation (interruptions lasting >14 days), with time to all-cause acute care visits as a secondary outcome. The intention-to-treat effect will be estimated using both propensity score and instrumental variable approaches. A range of sensitivity analyses will assess the robustness of our results, including cohort and timeline restriction, alternative definitions of exposure and outcome and alternative estimation strategies.

The protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Institute and the Simon Fraser University Office of Research Ethics. All data are deidentified, securely stored and accessed in accordance with provincial privacy regulations. Results will be disseminated to local advocacy groups and decision-makers, national and international clinical guideline developers, presented at international conferences and published in peer-reviewed journals electronically and in print.

Identity is a determinant of health-promoting behaviours such as physical activity and health-compromising behaviours such as smoking. This scoping review provides a comprehensive synthesis and comparison of the relationship between physical activity- and smoking-related identity and behaviour, and how these identities are defined and measured. Study participants’ personal, physical activity-related and smoking-related characteristics were considered if data were available. The review focuses on people aged 45 and above.

A search across 9 databases yielded 5801 unique publications. Ensuing careful screening, 268 peer-reviewed empirical studies met eligibility criteria, of which 45 concerned participants of 45+ age. Experts in the field contributed to validating and structuring the narrative.

Findings revealed the existence of an intricate, enduring direct and indirect relationship between identity and behaviour for physical activity and smoking. Numerous similarities and differences in this relationship, as well as in identity-related terminology and measurement tools used, were identified. In essence, endorsing an identity related to physical activity and smoking abstinence was found to be important for becoming physically active and quitting smoking successfully, respectively. Identity processes, encompassing identity formation, maintenance, change and loss, were detected as applicable to both physical activity and smoking, although differences were observed between the two behaviours. Characteristics such as gender, age and behavioural history emerged as relevant in shaping smoking-related and physical activity-related identities.

Despite variances, findings suggest that the relationship between identity and behaviour, including associated processes, may not fundamentally differ between health-promoting and health-compromising behaviours. Avenues for future research, including exploring causality between identity and behaviour, are proposed.

For several decades, mortality has decreased more rapidly among individuals with a higher socioeconomic position than among those with a lower position. This widening social inequality gap has increasingly been recognised as an important aspect of public health research and policies. The objective of this study was to examine trends in educational inequality in healthy life expectancy (HLE) in Denmark between 2010 and 2021 at the age of 30 years.

The study is a population-based study based on register data on longest attained education, standard life tables and self-reported health information from nationwide health surveys.

The study is conducted among the general adult population in Denmark.

Participants include respondents from the Danish National Health Survey and the Danish Health and Morbidity Survey in 2010, 2013, 2017 and 2021 aged ≥30 years.

Expected lifetime in good self-rated health, with no long-standing illness and with no activity limitations was estimated by Sullivan’s method, and educational inequality was expressed by the Slope Index of Inequality.

Between 2010 and 2021, educational inequality in HLE increased among both men and women for long-standing illness (5-year trend: +1.1 and +1.2 years) and activity limitations (+2.4 and +2.6 years) but remained stable among men (+0.1 year) and decreased among women (–0.3 year) for self-rated health. For the latter two indicators, the inequality gap narrowed after 2017.

Trends in educational inequality in HLE in Denmark 2010–2021 vary by health indicator. Steadily widening gaps were demonstrated for long-standing illness, while narrowing gaps were seen after 2017 for activity limitations and self-rated health. Future studies are encouraged to explore potential health risk behaviours that may explain or modify these inequality trends.

This study aimed to assess the pattern of disease and predictors of mortality among critically ill geriatric patients admitted to the intensive care unit at a teaching hospital.

A single-centre retrospective cohort study.

Medical-surgical intensive care unit of Tibebe Ghion Specialized Hospital, Bahir Dar, Ethiopia.

We enrolled 296 critically ill patients (age 60+) admitted to the intensive care unit who stayed for more than 2 hours. Those patients with missing or incomplete records were excluded.

The primary outcome of this study was the time to death within 30 days following intensive care unit admission.

In this cohort, the overall mortality rate of geriatric patients in the intensive care unit was found to be 42.9%. The incidence rate of mortality was 6.3 deaths per 100 person-days observation. Acute kidney injury (adjusted HR=2.36, 95% CI: 1.16, 3.68), coexisting diseases (adjusted HR=1.66, 95% CI: 1.13, 2.42), the presence of shock (adjusted HR=2.27, 95% CI: 1.66, 4.53) and mechanical ventilation (adjusted HR=1.82, 95% CI: 1.14, 2.89) were predictors of mortality in the intensive care unit.

The mortality rate in the intensive care unit among geriatric patients was high. Predictors of mortality in this population of critically ill geriatric patients included acute kidney injury, the presence of shock, coexisting diseases and mechanical ventilation in the intensive care unit.

Mental health problems are important causes of disability and economic costs worldwide. Randomised clinical trials examining the treatment of mental health disorders measure heterogeneous outcomes, causing difficulties in data synthesis, interpretation and translation into clinical practice. The aim of the Patient Important Outcomes in Psychiatry (PIO-Psych) Initiative is to develop an overarching, transdiagnostic research-based and consensus-based core outcome set for adult mental health disorders.

The development of the PIO-Psych transdiagnostic core outcome set will include three phases: (1) a systematic scoping review of the literature to develop the initial list of outcomes for the Delphi study; (2) a Delphi study in three rounds including people with lived experience of mental health disorders and their relatives, clinicians, researchers and others (administrators, mental healthcare policymakers, philosophers); (3) a hybrid consensus meeting to agree on the final overarching, transdiagnostic core outcome set and corresponding time points of assessment of each outcome.

Ethical approval is not applicable to this study according to the Research Ethics Committee of the Capital Region of Denmark, as it is not an interventional study. All data will be reported anonymously, and it will not be possible to identify study participants. Results will be disseminated via stakeholder and research networks and peer-reviewed publications.

The PIO-Psych Initiative was pre-registered with COMET (Core Outcome Measures for Effectiveness Trials) on 17 May 2024 (https://www.comet-initiative.org/Studies/Details/3125).

This longitudinal study aimed to document shifts in specialty preferences, career pathways and intended practice locations among medical students following the implementation of structured career initiatives during the 2023–2024 academic year.

A longitudinal observational survey study.

A private, not-for-profit institution, VinUniversity in Hanoi, Vietnam during the 2023–2024 academic year.

All year 2, year 3 and year 4 medical students (n=144 eligible), of whom 105 (73%) completed both baseline and follow-up surveys.

Structured career counselling initiatives introduced at the start of the academic year, including academic mentoring, clinical mentoring, hands-on clinical exposure in year 4 and multiple career counselling activities.

The primary outcome was change in specialty preference over time, measured by students’ self-reported first-choice specialty at baseline and follow-up. Secondary outcomes included shifts in factors influencing career decisions (eg, personal interest, income and family expectations), intended practice location (domestic or international) and preferred career pathways (residency, Specialist Level I, master’s degree or direct workforce entry).

Personal interest remained the strongest influence on specialty choice from baseline to follow-up (mean scores 4.27 vs 4.36 on a 5-point scale). A notable decrease occurred in the importance of income (3.82 to 3.22; p

Noticeable shifts in specialty preferences and career pathways were observed after a series of career initiatives were implemented. Although these trends coincided with the new programmes, further qualitative research is needed to elucidate how and why these career initiatives may have influenced decision-making. Informed by these findings, medical educators can refine interventions to support students’ evolving preferences and ultimately strengthen healthcare workforce distribution.

Cholecystitis is a highly prevalent disease that imposes a substantial burden on the healthcare system. Despite strong underlying evidence, guideline adherence in the treatment of cholecystitis remains low. Moreover, important gaps in knowledge persist that must be addressed to optimise existing guidelines. The primary aim is to assess the nationwide variation in cholecystitis treatment and identify opportunities to improve guideline adherence. Secondary aims include determining the best cystic duct closure method; the best model to predict concomitant choledocholithiasis; the optimal treatment for cholecystitis lasting 7 days or more at diagnosis and the optimal strategy for gallbladder drainage and post-drainage care.

The Dutch CHESS is a multicentre observational cohort study, including 67 out of 69 Dutch hospitals. From 1 April to 30 September 2024, all patients diagnosed with cholecystitis (Tokyo Guidelines definition) will be prospectively identified. Data on patient characteristics, treatment and outcome (with 6-month follow-up) will be collected to address the primary and secondary aims. For the primary aim, guideline adherence is defined as the percentage of patients who undergo early cholecystectomy for cholecystitis lasting 0–7 days. Current adherence, nationally and for each individual hospital, along with predictors of adherence, will be determined. The adherence of each hospital will be set against the national average and best practices. To further support improvement, the impact of guideline adherence on total hospital stay and morbidity will be determined. Three months after performance feedback to the participating hospitals, the impact on local practice will be assessed through questionnaires. Subgroup analyses and statistical methods for addressing both the primary and secondary aims are predefined in this protocol.

The Medical research Ethics Committees United reviewed the protocol and decided that the Dutch Medical Research Involving Human Subjects Act is not applicable (reference Number: W23.225). Approval was obtained from the institutional review board and board of directors at each participating hospital. Results will be disseminated through peer-reviewed publications and conference presentations.

ClinicalTrials.gov, NCT06349863; Pre-results.

To evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antitumour activity of AMG 404, a fully human IgG1 monoclonal antibody targeting programmed cell death-1, in patients with advanced solid tumours.

First-in-human phase I study comprising eight dose expansion cohorts, including cohorts with microsatellite instability-high (MSI-H) tumours and non-small cell lung cancer with high programmed death-ligand 1 expression (NSCLC/PDL1-H, tumour proportion score ≥50%).

Conducted across 28 global sites.

This study enrolled adult patients with histologically or cytologically confirmed metastatic or locally advanced solid tumours not amenable to curative treatment with surgery or radiation. The inclusion criteria included a life expectancy of >3 months, ≥1 measurable or evaluable lesion per modified Response Evaluation Criteria in Solid Tumours (RECIST) V.1.1, an Eastern Cooperative Oncology Group performance status of ≤2 and adequate haematological, renal and hepatic function. Patients with prior treatment with checkpoint inhibitors, primary brain tumour or untreated or symptomatic brain metastases and leptomeningeal disease and history of other malignancy within the past 2 years were excluded.

The planned doses were 240 mg, 480 mg and 1050 mg of AMG 404 administered every 4 weeks (Q4W).

Primary endpoints were dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, changes in vital signs and clinical laboratory tests. Secondary endpoints included PK parameters, incidence of antidrug (AMG 404) antibodies and antitumour activity assessed per modified RECIST V.1.1 (objective response, duration of response, progression-free survival (PFS), disease control and duration of stable disease).

A total of 171 patients were enrolled; 168 were treated. Median (range) follow-up was 36.3 weeks (1.6–137.1). No DLTs were observed. Grade 3 and serious treatment-related adverse events occurred in 16 (9.5%) and 12 (7.1%) patients, respectively. The 480 mg Q4W dose was selected as the recommended phase II dose. AMG 404 serum exposure increased approximately dose proportionally. The objective response rate (80% CI) was 19.6% (15.7–24.1) for the overall population and 36.6% (26.4–47.8) and 30.8% (14.2–‍52.3) for cohorts with MSI-H tumours (n=41) and NSCLC/PDL1-H (n=13), respectively. The overall disease control rate (80% CI) was 54.8% (49.5–59.9). The median (80% CI) PFS was 3.7 (3.5–4.5) months for the overall population and 14.8 (9.0–not estimable) and 4.4 (2.2–9.7) months for cohorts with MSI-H tumours and NSCLC/PDL1-H, respectively.

AMG 404 monotherapy was tolerable at the tested doses, with encouraging antitumour activity observed across tumour types.

NCT03853109.

A ‘cluster’ is an area with a higher occurrence of tuberculosis (TB) than would be expected in an average random distribution of that area. Tuberculosis clustering is commonly reported in Ethiopia, but most studies rely on registered data, which may miss patients who do not visit health facilities or those who attend but are not identified as having TB. This makes the detection of actual clusters challenging. This study analysed the clustering of pulmonary TB and associated risk factors using symptom-based population screening in Dale, Ethiopia.

A prospective population-based cohort study.

All households in 383 enumeration areas were visited three times over a 1-year period, at 4-month intervals.

Individuals with pulmonary TB aged ≥15 years with demographic, socioeconomic, clinical and geographical data residing in 383 enumeration areas (ie, the lowest unit/village in the kebele, each with approximately 600 residents).

Pulmonary TB (ie, bacteriologically confirmed by sputum microscopy, GeneXpert or culture plus clinically diagnosed pulmonary TB) and pulmonary TB clustering.

We identified pulmonary TB clustering in 45 out of the 383 enumeration areas. During the first round of screening, 39 enumeration areas showed pulmonary TB clustering, compared with only 3 enumeration areas in the second and third rounds. Our multilevel analysis found that enumeration areas with clusters were located farther from the health centres than other enumeration areas. No other determinants examined were associated with clustering.

The distribution of pulmonary TB was clustered in enumeration areas distant from the health centres. Routine systematic community screening may be costly, but using existing health infrastructure with health extension workers through targeted screening, they can identify and refer persons with TB symptoms more quickly for diagnosis and treatment, thereby decreasing the duration of disease transmission and contributing to the reduction of TB burden.

Osteoarthritis (OA) is a multifactorial disease in which low-grade inflammation is considered to play a pivotal role. Although colchicine is a widely used anti-inflammatory drug in the treatment of gout, its effect in OA is still disputed due to inconsistent results of short-term clinical trials. Therefore, we aim to evaluate the effect of long-term colchicine 0.5 mg once daily on the incidence of knee or hip replacements in patients with knee or hip OA.

The ECHO trial is a prospective, multicentre, randomised, double-blind, placebo-controlled, phase III trial in which 1200 participants with knee or hip OA tolerant to colchicine during a 30-day run-in period will be 1:1 randomised to colchicine 0.5 mg once daily or matching placebo using concealed allocation. The primary endpoint is the time from randomisation to the first knee or hip replacement assessed up to 4.5 years. Secondary endpoints include course of pain, physical function, joint space narrowing, low-grade inflammation, quality of life, clinical or radiological onset of OA in a new joint group other than present at baseline, number of participants using pain medication during the study, onset of new cardiovascular events (ie, myocardial infarction, ischaemia-driven coronary revascularisation, ischaemic stroke, peripheral artery disease or cardiovascular death) and direct and indirect costs related to treatment and disease burden due to OA. Harm-related endpoints include the number of (serious) adverse events, the number of withdrawals due to (serious) adverse events and changes in laboratory data (ie, serum creatinine, estimated glomerular filtration rate and alanine transferase) throughout the study. The primary analysis will be performed according to the intention-to-treat principle.

This trial has been approved by the Medical Ethics Review Committee East-Netherlands. Findings will be presented at scientific meetings and published in a peer-reviewed scientific journal.

NCT06578182.