This study aimed to quantify how patient risk factors relate to COVID-19 severity across categories 1–5 in a prospective, hospital-based cohort. We hypothesised that greater severity would be associated with higher odds of intensive care unit (ICU) admission and in-hospital mortality. Secondary aims were to assess associations with age, viral variants, symptom clusters, lymphocyte count, fasting blood glucose and cytokine profiles.

Prospective cohort study.

A secondary-care/tertiary-care hospital and linked community settings in Cheras, Kuala Lumpur, Malaysia.

This study was nested within the COVGEN project, a prospective COVID-19 cohort conducted at Hospital Canselor Tuanku Muhriz UKM (HCTM), Cheras Health Clinic and the Bandar Tun Razak COVID-19 Assessment Centre in Cheras, Kuala Lumpur, Malaysia, from 1 August 2021 to 31 October 2022. 2532 participants were enrolled at baseline. Eligible participants were Malaysian citizens aged 12–18 years (paediatric/adolescent) or ≥18 years who had reverse transcription-polymerase chain reaction–confirmed COVID-19 at recruitment and resided in Kuala Lumpur or Selangor. Patients who had a clinically unstable condition and those who declined participation (personally or via a next-of-kin or legal representative) were excluded. This analysis included 559 patients hospitalised at HCTM; after excluding five with incomplete questionnaires, 554 remained for analysis (413 admitted to general wards and 141 to ICUs). Categories 3–5 comprised hospitalised patients, whereas categories 1–2 included hospitalised individuals and a subset recruited from community settings.

Primary outcomes included disease severity (categories 4–5 vs 1–3), ICU admission and in-hospital mortality. Secondary outcomes included associations with age strata, viral variant (delta vs omicron), symptom clusters, lymphocyte count, fasting blood glucose and cytokines: interferon gamma-inducible protein 10, interferon gamma, interleukins 8, 10, 2, 6 and 7 and tumour necrosis factor alpha.

141 of 554 (25.5%) patients required ICU care. Compared with milder categories, category 5 was associated with markedly higher odds of ICU admission (OR 204.50; 95% CI 37.54 to 1114.18; p55 versus

An increasing clinical severity category was strongly associated with ICU admission and mortality. Age, delta infection, specific symptom clusters, lymphopenia, hyperglycaemia and pro-inflammatory cytokines identified higher-risk patients, supporting risk-stratified management and prioritisation for enhanced monitoring.

To establish consensus definitions for non-visually impairing eye conditions (NVICs) and their methods of assessments to provide standards for use in population-based eye surveys.

A literature review of NVICs in sub-Saharan Africa, a questionnaire of inquiry based on the literature review developed by an expert panel and a modified Delphi exercise with three iterative rounds with eye health experts.

Eye health academia and community eye health in Nigeria.

Nigerian ophthalmologists, including subspecialists experienced in population-based eye health surveys.

Definitions and statements where at least 70% of the respondents agreed or strongly agreed.

Forty-two ophthalmologists practising in Nigeria with experience in conducting population-based eye health surveys were invited to take part in the Delphi exercise. There were three rounds with response rates of 39/42 (92.9%) in round 1, (94.9%) in round 2 and 100% in round 3. Consensus for NVICs to be included in population-based eye surveys, their definitions and methods for assessment was reached by the third round.

We propose case definitions for NVICs to be assessed in population-based eye surveys through a modified Delphi approach with an expert panel of ophthalmologists from across Nigeria. These case definitions will allow for standardisation of NVICs in population-based eye surveys to assess the prevalence and magnitude of the different types of NVICs for planning purposes. Further studies are needed to validate these case definitions and inform their evolution.

Breast screening uptake remains low in parts of the UK, partly due to barriers including limited transport access. Offering free transport to screening appointments may help address this and improve uptake. This general practitioner (GP) cluster-randomised feasibility trial will assess whether offering free door-to-door transport alongside routine screening invitations increases attendance.

Eight general practices in Yorkshire will be randomised to either the intervention (routine invitation plus information about booking free door-to-door transport) or control (routine invitation only) group. Around 8000 women due for routine breast screening will be included. Primary feasibility outcomes include GP recruitment and randomisation, intervention fidelity, proportion of women from the 10% most deprived areas, acceptability and data transfer processes. Secondary outcomes include understanding travel behaviour, cost-effectiveness and screening uptake. Data will be collected from routine National Health Service (NHS) screening records, data linkage with NHS England, travel surveys and qualitative interviews exploring experiences and acceptability. Patient and public involvement is embedded throughout with members contributing to advisory and oversight roles.

The trial has received ethical approval from the London–Harrow Research Ethics Committee, Section 251 approval from the Confidentiality Advisory Group and other relevant regulatory bodies. The University of Hull is the study sponsor. Results will be disseminated through peer-reviewed journal publications, conference presentations and plain English summaries for participants and the public. Findings will inform the feasibility and design of a potential larger trial to improve breast screening uptake via transport support.

ISRCTN17087898.

Osteogenesis imperfecta (OI) is the most common inherited cause of bone fragility (approximately 1 in 16 000). People with OI suffer bone fragility causing fractures, pain and deformity; sarcopenia causing fatigue and poor endurance; aortic root dilatation and hearing loss. No drug currently has market authorisation to treat OI in Europe. Current standard-of-care is multidisciplinary, with pharmacological interventions—primarily bisphosphonates—directed at increasing bone mass; however, such interventions are of equivocal efficacy. The structural damage that can accumulate as a result of repeated fractures over time may not be reversible. The lack of a treatment with clearly defined efficacy in terms of reducing fracture frequency or the sarcopenia, that is increasingly recognised in this condition, leads to the consideration of alternatives based on what is known about the molecular pathophysiology of the condition. For reasons that are currently unclear, transforming growth factor beta (TGFβ) pathway signalling is increased in OI, and both studies in mouse models and more recently also in humans suggest that reducing TGFβ pathway signalling could be of benefit in OI. This demonstrator project tests the hypothesis that losartan, an antihypertensive agent known to reduce circulating TGFβ, will reduce bone turnover and bone loss and have a positive effect on muscle function and quality of life in adults and older adolescents with OI.

This is a phase 2/pilot, open-label, dose-escalating study. This study aims to identify the effective dose for losartan in this population to inform the design of a pivotal phase III study. The study aims to recruit 30 adolescents and adults aged 16 years and above with OI across secondary care study sites in the UK and Italy. Participants will be recruited from the patient populations attending for treatment of OI at the participating hospital sites or referred by clinicians at the Participant Identification Centres (PIC sites). Participants will be randomised to one of three ‘final doses’—25, 50 or 75 mg losartan once daily. All participants will start on 25 mg once daily. Those assigned to higher ‘final doses’ will increase in 25 mg once daily increments on day 8 and day 15 following safety assessments. The primary outcome measures are to establish the effective dose of losartan in OI patients, based on maximal reduction in the bone resorption marker carboxy-terminal crosslink of type I collagen telopeptide (CTX) over the 24-week period of the study.

Secondary outcome measures are to determine the changes in proxy efficacy outcomes for bone (turnover, mass, architecture and strength) using blood tests, high-resolution peripheral quantitative CT (HRpQCT), dual-energy X-ray absorptiometry (DXA) and muscle (strength) using the ‘Timed Up and Go’ test. In addition, the changes in quality of life, including pain and fatigue, will be evaluated by using a disease-specific tool (OI-QOL) and a validated generic tool (EQ-5D-5L-VAS).

In the UK, the study protocol and amendments have been approved by the London Bridge Research Ethics Committee (REC reference: 23/LO/015) and by the Medicines and Healthcare products Regulatory Agency (MHRA). In Italy, the study protocol and amendments have been approved by the Italian and European ethics and regulatory authorities (Clinical Trials Information System European Union (CTIS EU) portal according to EU Regulation 536/2014). Final version of study protocol: Version 3.2, 05.03.2025. Final results will be disseminated in peer-reviewed journals through local OI, orthopaedic and other relevant clinical networks and at national and international meetings. Sheffield Children’s National Health Service Foundation Trust (UK) and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Rizzoli (Italy) are the joint study sponsors.

ISRCTN (ISRCTN13317811).

To identify and explain the challenges of effective pain management in patients with cancer in Iran.

A convergent mixed-methods study.

Oncology departments and palliative care units across multiple healthcare institutions in Iran.

Quantitative phase: 320 healthcare providers, including anaesthesiologists, general practitioners, oncologists, nurses and pharmacists, selected via convenience sampling. Qualitative phase: 10 stakeholders, including patients, caregivers, policy makers and clinicians.

Quantitative data were collected using a psychometrically validated 23-item questionnaire assessing knowledge, attitudes and perceived barriers to cancer pain management. Qualitative data were obtained through semistructured interviews and analysed using Graneheim and Lundman’s content analysis method with MaxQDA software. Integration was performed using a side-by-side approach.

Quantitative data showed that over 65% of providers did not routinely assess pain, and only 29.1% believed pharmacological treatments were effective. Qualitative analysis identified 13 barriers across three domains—professional, patient and organisational—spanning physical, psychological, social and spiritual dimensions. Integrated findings revealed consistent patterns of underassessment, legal and cultural resistance and lack of interdisciplinary collaboration. These converging challenges highlight the need for holistic, system-level reform.

The convergence of quantitative and qualitative data reveals a multilayered system of barriers, professional, patient-related and organisational—rooted in physical, psychological, social and spiritual dimensions. These interlinked challenges contribute to fragmented pain management and limited interdisciplinary coordination. Addressing them requires a holistic reform strategy that integrates structural, cultural and clinical solutions.

Pneumonia and diarrhoea are two of the major causes of child mortality globally. Countries affected by conflict and other humanitarian emergencies, such as Somalia, have a particularly high burden of these diseases. Published reports from UNICEF and WHO have shown that various factors, including social, economic and environmental factors, are all associated with the occurrence of childhood pneumonia and diarrhoea. The objective of this study was to determine the prevalence, burden and associated sociodemographic determinants of pneumonia and diarrhoea among children younger than 5 years (under-5 children) in Somalia.

A community-based survey using an interviewer-administered questionnaire was conducted employing a modified WHO Expanded Program on Immunization (EPI) 30-Cluster sampling technique to identify households and respondents in nine selected districts across six member states in Somalia. The interviewers began selecting households starting from house number 1 and continued until 75 households were surveyed in each cluster.

We considered the catchment areas of 12 target maternal and child health (MCH) centres as our study areas. Villages were considered as primary sampling units (PSU) while households within villages were considered as secondary sampling units, where women (with under-5 children) within households were the respondents.

A total of 36 clusters (villages) were selected from the catchment areas of 12 target MCH centres. All households within the selected villages’ PSUs were listed. The interviewer started interviewing from house number 1 and continued till 75 households were covered to conduct interviews with mothers of under-5 children. Data collection took place between October and December 2023.

The prevalence and burden of childhood pneumonia and diarrhoea were estimated. A logistic regression model was employed to examine the determinants of childhood pneumonia and diarrhoea.

A total of 2483 under-5 morbidities were reported, 1712 probable pneumonia cases and 825 diarrhoea cases. Our calculations suggest that the prevalence of overall under-5 morbidity was 458.4 per 1000 children (95% CI 444.3 to 472.6) in the last 90 days. The prevalence of pneumonia and diarrhoea was 316.0 (95% CI 303.5 to 328.8) and 152.3 (95% CI 142.2 to 162.8) per 1000 under-5 children, respectively. A total of 70 under-5 deaths occurred in the past year, of which 37 were infants. Our exploration depicts an under-5 mortality rate of 39.3 deaths per 1000 live births per year (95% CI 30.6 to 49.7), and the infant mortality rate was 20.8 per 1000 live births per year (95% CI 14.8 to 28.6) in the study area, which is much lower than earlier estimates. The crude birth rate was 106.6 per 1000 population, and the stillbirth rate was 149.8 per 1000 births (95% CI 134.9 to 165.7), which is very high. We explored probable causes of 70 under-5 deaths and found that the highest proportion of under-5 deaths (22.9%) was due to acute respiratory infections (ARI), and about 15.7% were due to diarrhoea. Among other probable causes, congenital diseases (12.9%), accidents (11.4%) and measles (8.6%) were noteworthy.

This study revealed a high burden of pneumonia and diarrhoea among the studied population in Somalia. The study also identified important sociodemographic and environmental determinants that tend to increase the risk of pneumonia and diarrhoea among under-5 children.

To evaluate the diagnostic accuracy of CT in identifying small and large bowel obstruction and associated complications, including ischaemia and perforation, in adult patients.

Systematic review and meta-analysis reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy reporting guidelines.

Ovid MEDLINE and Embase were searched from 1946 to 20 February 2025.

The study included randomised controlled trials, cohort studies and case–control studies evaluating the diagnostic accuracy of CT for bowel obstruction in adults (aged ≥18 years). Only studies published in English were included. Conversely, case reports, editorials, conference abstracts without full data and studies focusing exclusively on paediatric populations or animal models were excluded.

Three reviewers independently extracted data on study characteristics, CT modality, diagnostic accuracy metrics (sensitivity, specificity and predictive values) and complications. Risk of bias was assessed using the QUADAS-2 tool. A random-effects meta-analysis was conducted. Heterogeneity was assessed using I² and Tau² statistics.

Sixty-five studies with 9418 patients were included. The pooled sensitivity and specificity of CT for bowel obstruction were 90% (95% CI 78 to 96; I²=56%, Tau²=0.36) and 88.8% (95% CI 78.0 to 94.8; I²=65%, Tau²=0.35), respectively. For bowel ischaemia, CT showed a pooled sensitivity of 47.0% (95% CI 32.4 to 59.9; I²=0%, Tau²=0.00) and specificity of 85.3% (95% CI 77.9 to 89.5; I²=1%, Tau²=0.45). Multidetector CT (MDCT) outperformed older modalities across all endpoints. Ischaemia was present in 22.05% of all cases, with higher rates in small bowel obstruction. Perforation and mortality rates were 3.98% and 4.40%, respectively. No significant publication bias was detected, and the certainty of evidence was graded as moderate for most diagnostic accuracy outcomes.

CT, particularly MDCT, offers high diagnostic accuracy for bowel obstruction and is a critical tool for detecting serious complications such as ischaemia and perforation. However, sensitivity for ischaemia remains modest. Standardised protocols and prospective studies are needed to enhance early identification and optimise care pathways.

To project the future burden of cancer mortality in India by forecasting age-standardised mortality rates (ASMRs) for 23 major cancer types up to the year 2030, providing crucial evidence for long-term health planning and resource allocation.

A retrospective analysis and time-series forecasting study. Participants Aggregated, national-level cancer mortality data for the population of India from 2000 to 2019 were used.

Aggregated, national-level cancer mortality data for the population of India from 2000 to 2019 were used.

Annual ASMR data for 23 cancer types were obtained from the Global Cancer Observatory. Autoregressive Integrated Moving Average was employed to forecast ASMR until 2030. For each cancer site, the model with the minimum Bayesian Information Criterion was chosen for males, females and both sexes combined.

The projections reveal diverging mortality patterns across different cancer types. For both genders, the ASMR for mouth oropharynx had the highest estimation of 13.75 (95% CI: 12.69 to 14.81) per 100000 population by 2030 from a baseline of 10.21 in 2000. Breast and cervical cancer showed estimations of 6.62 and 6.03 in 2030, respectively. Conversely, mortality rate projections for several cancers declined, most notably cervical cancer and stomach cancer

Our projections indicate a rise linked lifestyle and metabolic factors and a decline in infection-related and tobacco-related cancers. These underscore the need for strengthening preventive and screening programmes for the former, while continuing to invest in successful interventions for the latter.

In current clinical practice, breast cancer is treated according to hormone receptor and human epidermal growth receptor 2 expression (HER2) status, which play an important role in disease management and overall prognosis. Trastuzumab deruxtecan (T-DXd) has been studied in multiple global prospective DESTINY-breast trials. Recent marketing authorisation for T-DXd has been granted from Health Canada for HER2-positive breast cancer who have received prior treatment with trastuzumab emtansine, or at least one prior anti-HER2-based regimen in the metastatic setting, or who have received a prior anti-HER2-based regimen in the neoadjuvant or adjuvant setting and developed disease recurrence during or within 6 months of completing neoadjuvant or adjuvant therapy. T-DXd is also indicated for HER2-low unresectable and/or metastatic breast cancer (mBC) patients who have received at least one prior line of chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. However, there is a paucity of evidence assessing T-DXd in the real-world setting. As such, the overarching aim of this study is to generate Canadian real-world evidence on discontinuations and treatment modifications for patients with HER2+ and HER2-low mBC undergoing treatment with T-DXd.

This is a hybrid, longitudinal cohort study design leveraging patient support programme (PSP) secondary data with additional primary data collection to assess study treatment-related outcomes among patients with HER2+ and HER2-low mBC receiving treatment with T-DXd. Mainly, this study will leverage secondary data from the PSP, which will include clinical and demographic characteristics as well as duration, modification and intensity of treatment information for patients while enrolled in the PSP. These data will be supplemented with primary data, which will be collected via a patient questionnaire and include additional self-reported clinical and demographic characteristics not captured within the PSP, including follow-up data on therapies received, treatment discontinuation information after the PSP closure and frequency of CT scans and cardiac monitoring scans.

The study protocol was approved by the Advarra Institutional Review Board on 13 December 2023 (ID: D133HR00037). Findings will be disseminated by publication in peer-reviewed journals, through oral and poster presentations for various audiences, websites and scientific meetings. Written informed consent will be obtained from all patients prior to agreeing to participate in this study.

Participant recruitment for primary data collection began on 22 April 2024 and was completed on 8 October 2024. Primary data collection for follow-up will continue through up to 12 months after the date of the last enrolment.

NCT06386263.