This study aims to describe the characteristics of hospitalised COVID-19 patients in a tertiary care hospital close to an international airport in Japan and to compare these characteristics among different waves during the pandemic.

Retrospective observational study.

Tertiary care centre in Japan.

All patients diagnosed with COVID-19 who were hospitalised between January 2020 and April 2022 were included.

Clinical characteristics, characteristics of admission, treatments and outcomes were investigated and compared among six pandemic waves.

A total of 827 patients were included. The median age was 58.0 years. More than half of the patients (58.3%) had at least one comorbidity. The majority of patients (89.0%) were domestically infected patients admitted under the Infectious Diseases Law, while the remaining patients (11.0%) were those diagnosed during airport quarantine and admitted under the Quarantine Act. Hospital-acquired COVID-19 infection occurred in 7.0% of cases, and mainly during the sixth wave. Overall, some form of oxygen therapy, high-flow oxygen devices, invasive mechanical ventilation (IMV) and extracorporeal membrane oxygenation was provided in 46.3%, 10.4%, 4.5% and 1.5% of cases, respectively. Only 1.8% of patients were treated in the intensive care unit (ICU), and 59.5% of patients on IMV were managed in the non-ICU ward. The in-hospital mortality rate was 5.8%. Median age, percentages of some comorbidities, vaccination coverage, medications for COVID-19, types of supportive care and ICU admissions differed significantly among waves.

This study suggests that patient characteristics, vaccination coverage, standard of treatment and severity of illness changed across waves during the COVID-19 pandemic. Intensive care delivery in non-ICU wards was unavoidable due to limited ICU capacity, which may be a key consideration when preparing for future pandemics.

The global need for developing comprehensive mental healthcare systems for children and adolescents has been increasingly evident. The system-of-care (SOC) model in the USA is among the most studied cases for such a system, which demonstrates how integrated services, encompassing psychiatric care, can effectively support children and adolescents with severe emotional disturbance. Over the past decades, the SOC framework has been widely expanded, with nearly every state in the USA receiving federal funding to implement or expand the SOC initiatives. The number of studies investigating the efficacy of the SOC is increasing, but no systematic review of the instruments for the evaluation of the implementation of the SOC exists today. This protocol paper documents the plan of a systematic review, which aims to identify and synthesise the existing instruments, which are designed and used to evaluate the implementation of the SOC.

This systematic review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Protocol guidelines. To identify relevant studies, we will perform a comprehensive search in five databases: PubMed, PsycINFO, ERIC, Social Work Abstracts and Web of Science. The title and abstracts of all searched articles will be screened independently by two reviewers according to the eligible criteria. Full-text screening of potentially relevant articles will be performed by at least two independent reviewers. A summary of included articles will describe the availability, progress and cultural adaptability of instruments.

The current systematic review will be solely based on previously reported data and will not involve new data collection. There are no concerns that require ethical vetting. Findings of the review will be disseminated through conference presentations and publication in a peer-reviewed journal.

1065693.

Workplace violence (WPV) is a significant occupational hazard in healthcare, negatively impacting healthcare workers’ (HCWs) mental health and quality of care. Psychosocial safety climate (PSC), an organisational factor emphasising psychological well-being, may influence how HCWs perceive, experience and cope with WPV. However, its role in shaping HCWs’ coping strategies remains underexplored. This study aims to examine the relationship between PSC and coping mechanisms among HCWs experiencing WPV in public hospitals.

This explanatory sequential mixed-method study comprises two phases. In Phase 1, a multicentre cross-sectional survey will be conducted among at least 440 HCWs working in Malaysian public hospitals that are selected through multistage random sampling. PSC, WPV exposure and coping mechanisms will be assessed using validated tools, including the Psychosocial Safety Climate (PSC-12) scale and the Brief Coping Orientation to Problems Experienced (Brief COPE) questionnaire. Linear regression will examine the association between PSC and coping mechanisms among HCWs exposed to WPV. In Phase 2, 6–12 HCWs with WPV experience in the past year and employed in high-PSC departments will be selected via criterion sampling with maximum variation for in-depth interviews. A semistructured interview guide based on the Transactional Model of Stress and Coping will be developed and pilot tested. Data will undergo thematic analysis until saturation is reached, identifying key themes on how PSC influences coping. Findings from both phases will be integrated using joint display analysis to inform PSC-driven interventions that promote coping and reduce WPV impacts among HCWs.

The study has been approved by the Ministry of Health Medical Research and Ethics Committees and Universiti Teknologi MARA Research Ethics Committee. Informed, written consent will be obtained from all participants. Findings will be disseminated to the Ministry of Health and through peer-reviewed publications.

Immigrant populations, particularly undocumented immigrants, are often considered ‘hidden’ or ‘hard to reach’ in research. This invisibilisation—under-representation or exclusion in data collection—leads to data inequities and biased findings that fail to capture their unique experiences. Starfish sampling mitigates selection bias and improves access to invisibilised populations by recruiting ‘seed’ participants at randomly selected times and locations and leveraging their social networks to recruit the next wave of participants. In this protocol paper, we outline the sampling strategy for the BRAVE (Building community, Raising All immigrant Voices for health Equity) study, a multi-site, cross-sectional survey examining the relationship between immigration history and sexual and reproductive health (SRH) service utilisation among Asian immigrant women in the USA. This protocol is an adaptation of novel starfish sampling in combination with various data tools and a community-based participatory research approach.

Using data from the American Community Survey and insights from community partners, we will conduct community mapping across four study sites (Atlanta, Houston, Los Angeles County and New York City). We will select census tracts that reflect the primary ethnic groups of interest and diverse socioeconomic backgrounds. From these selected census tracts, we will construct a venue universe by identifying key activity areas for Asian immigrant women through data scraping from online sources. We will then randomly select venue-date-time combinations and deliberately choose various community engagement events for recruitment. Culturally competent field officers who are fluent in Asian languages will recruit participants at these events. Participants can refer up to three peers from their social networks to take part in the survey. Results will be presented as descriptive statistics and logistic regression models to test the association between immigration history and SRH service utilisation.

The overarching BRAVE study protocol was approved by the University of California Los Angeles Institutional Review Board (IRB) (IRB-22–0493-AM-016). The results will be disseminated through academic journal publications and relevant data will be shared with our community partners.

To evaluate the effects of liberal transfusion strategy (trigger haemoglobin ≤90–100 g/L) compared with a restrictive strategy (trigger haemoglobin ≤70–80 g/L) on long-term neurological functional outcome in anaemic adult patients with acute acquired brain injury (ABI).

Systematic review and study-level meta-analysis of randomised controlled trials (RCTs).

MEDLINE, EMBASE, Cochrane from inception to 6 February 2025.

RCTs enrolling patients with acute ABI and anaemia (haemoglobin ≤100 g/L), comparing a liberal vs restrictive transfusion strategy.

Two reviewers independently identified eligible studies, extracted data and assessed risk of bias. We performed random-effects meta-analysis of RCTs and applied Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the certainty of evidence. Our primary outcome was an unfavourable neurological functional outcome, using the Glasgow Outcome or modified Rankin scales.

Five trials enrolling 2364 patients with acute ABI and anaemia were included in the primary analysis. Liberal transfusion reduces the risk of unfavourable neurological outcome (risk ratio (RR)=0.89, 95% CI 0.84 to 0.95, high certainty). Liberal transfusion may reduce severe disability (RR=0.82, 95% CI 0.66 to 1.02, moderate certainty), and increase good recovery compared with restrictive transfusion (RR=1.29, 95% CI 0.95 to 1.76, low certainty). We found no difference in the risk of most adverse events, including death. Statistical heterogeneity was low (I²=0%–36%) for neurological outcomes.

In adults with acute ABI and anaemia, liberal transfusion reduces the risk of unfavourable outcome (high certainty) and possibly improves the chances of good recovery (low certainty) when compared with restrictive transfusion.

CRD42025628732.

Chronic subdural haematoma (CSDH) is a common neurosurgical condition in older adults, with a recurrence rate of approximately 7.1–13% after burr-hole drainage. Although surgical adjuncts such as subdural drains and middle meningeal artery embolisation may reduce recurrence, these are not suitable for all patients. Pharmacological strategies, including tranexamic acid, Goreisan and carbazochrome sodium sulfonate hydrate, have shown potential, but high-level evidence remains lacking. A prior retrospective study suggested that a triple oral regimen combining these agents may reduce recurrence. This randomised controlled trial aims to evaluate its efficacy and safety.

This is a prospective, multicentre, open-label, randomised controlled trial conducted across six hospitals in Ibaraki, Japan. A total of 180 patients undergoing first-time burr-hole surgery for CSDH will be randomised 1:1 to receive either triple therapy (Goreisan 7.5 g/day, carbazochrome sodium sulfonate hydrate 90 mg/day and tranexamic acid 750 mg/day for up to 90 days) or standard postoperative care. The primary outcome is recurrence requiring reoperation within 90 days. Secondary outcomes include time to recurrence and haematoma volume reduction on serial CT imaging. All analyses will follow the intention-to-treat principle, using logistic regression, Cox proportional hazards models and mixed-effects models.

Written, informed consent will be obtained from all participants at each participating hospital by trained staff from that hospital. The trial protocol has been approved by the ethics committee of the University of Tsukuba Hospital (approval no. TCRB23-025) and the Institutional Review Boards of all participating centres. Study findings will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. A summary of the results will also be provided to participating institutions and made publicly available in accordance with the BMJ Open data sharing policy.

jRCTs031240007.

To examine state-level variation in mental health screening practices for high school athletes in the USA and evaluate associations between screening protocols and adolescent depression-related and suicide-related outcomes.

Cross-sectional study of preparticipation examination (PPE) forms and Youth Risk Behaviour Surveillance System (YRBSS) data.

High school athletics across all 50 US states and the District of Columbia.

732 676 high school students who completed the 2021 YRBSS survey (grades 9–12).

Prevalence of depressive symptoms and suicide-related behaviours, measured using YRBSS items on sadness/hopelessness, suicide ideation, planning, attempts and suicide attempts resulting in injury. State-level PPE forms were reviewed for presence and depth of mental health screening, including Patient Health Questionnaire-4 (PHQ-4) and eating disorder (ED) risk questions.

Screening practices varied widely, ranging from no mention of mental health in some states to required evaluations with formal referral protocols in others. Of 732 676 students, 503 861 (68.7%) reported feeling sad or hopeless, 608 416 (83.0%) seriously considered suicide and 64 072 (8.8%) attempted suicide in the past year. States with required screening protocols had higher reported rates of depressive symptoms (71.0% vs 68.7%, p

High school athletes represent a vulnerable group in need of structured and standardised mental health screening. State-level screening policies were associated with lower suicide attempt rates, though causal inference is limited by the cross-sectional design. Standardised use of validated mental health tools may support early identification and intervention for at-risk adolescents.

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.

Infants born to pregnant women living with HIV (WLHIV) are at greater risk for morbidity and mortality and may also have poorer developmental outcomes as compared with infants who are not exposed to HIV. Nutrition interventions in pregnancy may affect developmental outcomes.

This study evaluated the effect of maternal vitamin D supplementation on infant development outcomes.

We conducted a secondary analysis of a randomised, triple-blind, placebo-controlled trial of maternal vitamin D supplementation from June 2015 to October 2019.

Antenatal care clinics in Dar es Salaam, Tanzania.

Pregnant WLHIV and their offspring.

Daily 3000 IU vitamin D₃ or placebo supplements taken during pregnancy and lactation.

Infants were assessed for cognitive, language and motor development at 1 year of age with the Caregiver Reported Early Development Instruments (CREDI).

A total of 2167 infants were eligible, and 1312 of them completed CREDI assessments at 1 year of age. Vitamin D supplementation had no effect on overall CREDI z-scores (standardised mean difference (SMD) 0.03, 95% CI –0.09, 0.15, p value 0.66). There was also no evidence of a difference between vitamin D and placebo groups in language (SMD 0.06, 95% CI –0.08, 0.21, p value 0.40), motor (SMD 0.02, 95% CI –0.09, 0.14, p value 0.69) or cognitive domain z-scores (SMD 0.05, 95% CI –0.08, 0.17, p 0.48).

Maternal vitamin D supplementation during pregnancy and lactation did not affect infant development outcomes.

ClinicalTrials.gov identifier: NCT02305927.

The standard treatment for unresectable head and neck cancer typically involves radiotherapy (RT) alone or chemoradiotherapy (chemo-RT). Non-squamous cell carcinomas exhibit relatively low radiosensitivity, limiting the efficacy of conventional photon RT. Carbon-ion (C-ion) RT, characterised by high linear energy transfer (LET) and high relative biological effectiveness (RBE), has shown promising outcomes in treating radioresistant head and neck cancers. However, local recurrences still occur, and further improvements in treatment outcomes are needed. To enhance the local control rate, an increase in dose-averaged LET (LETd) to the tumour was considered.

Following a simulation study, a clinical trial was conducted to optimise LETd using only C-ion therapy, and its safety was confirmed. However, in this clinical trial, LETd could only be increased to approximately 70 keV/μm. To further escalate LETd, multi-ion therapy using ions heavier than carbon was developed. Simulation studies demonstrated that multi-ion therapy incorporating carbon, oxygen and neon ions could increase LETd up to 90 keV/μm, regardless of tumour size, while maintaining high-dose uniformity within the tumour. Based on these results, a clinical study was planned to evaluate the safety of escalating LETd from 70 keV/μm to 90 keV/μm using multi-ion therapy. The primary objective of this study is to evaluate the safety of escalating LETd to the tumour using multi-ion therapy for head and neck cancer, with the secondary goal of identifying the maximum tolerated LETd.

This is a non-randomised, open-label, phase 1 study focused on LETd escalation. A maximum of 18 patients with histologically confirmed inoperable head and neck malignancies will be enrolled. All patients will receive multi-ion therapy using helium, carbon, oxygen or neon ions, either alone or in combination, at an RBE-weighted dose ranging from 57.6 to 70.4 Gy, delivered in 16 fractions (4 fractions per week) over 4 weeks. The specific dose will be determined according to histology. LETd escalation will begin at 70 keV/μm and will increase by 10 keV/μm increments, reaching a maximum of 90 keV/μm. The safety of multi-ion therapy will be assessed based on the frequency and severity of dose-limiting toxicities, monitored up to 90 days after the initial irradiation. Patients will be followed up according to the protocol for 180 days after the initial multi-ion therapy irradiation.

The study protocol has been approved by the National Institutes for Quantum Science and Technology Certified Review Board (#L24-002). The results will be published in a peer-reviewed journal and presented at a scientific conference.

jRCTs032240451.

To evaluate the impact of Japan’s COVID-19 state of emergency declarations on percutaneous coronary intervention (PCI) volumes using Seasonal AutoRegressive Integrated Moving Average with eXogenous variables (SARIMAX) modelling. This model offers methodological advantages by: (1) accounting for trends, seasonal variations and autocorrelation; (2) allowing the introduction of policy intervention periods as binary exogenous variables; and (3) enabling an accurate assessment of healthcare impacts during intermittent declaration phases while accounting for periods of subsidence.

Retrospective observational study using a SARIMAX model.

1377 acute care hospitals participated in Japan’s Diagnosis Procedure Combination (DPC) system between April 2018 and December 2021.

All patients who underwent emergency PCI (n=176 878) or elective PCI (n=272 811) during the study period, identified from a nationwide administrative database.

This study analysed the impact of Japan’s COVID-19 state of emergency declarations as policy intervention periods, which were implemented during four waves (April to May 2020, January to March 2021, May to June 2021 and July to September 2021). Months where more than half of the days fell within a state of emergency declaration were defined as intervention periods.

Primary outcome measures were nationwide changes in both emergency and elective PCI volumes during state of emergency periods compared with non-emergency periods, analysed through SARIMAX modelling. Secondary outcomes included regional analyses of changes in both types of PCI volumes across eight geographical regions of Japan and the distribution analysis of medical resources (DPC hospitals, hospital beds, physicians and board-certified cardiologists per million population) in each region.

Nationwide, emergency PCI volumes totalled 176 878 and elective PCI volumes 272 811 over the 45-month study period. SARIMAX modelling indicated that the state of emergency declarations were associated with significant reductions in both emergency PCI volumes (–211.4 cases/month, 95% CI –326.9 to –95.9; –5.4%) and elective PCI volumes (–632.4 cases/month, 95% CI –1045.9 to –219.0; –10.4%). Regional analyses showed varied effects, with some areas (eg, Hokkaido, Shikoku, Kyushu) experiencing non-significant volume decreases, potentially reflecting differences in medical resource distribution and capacity.

The COVID-19 state of emergency declarations in Japan were associated with decreased PCI volumes. Applying SARIMAX models to real-world data could allow us to examine the effects of various events on healthcare considering trends, seasonal variation and autocorrelation by incorporating events as exogenous variables.

Approximately, 20 million older adults undergo major elective surgery annually, yet less than 10% engage in advance care planning (ACP). This is a critical missed opportunity to optimally engage in patient-aligned medical decisions and communications in the perioperative setting. The PREPARE ACP programme (easy-to-read advance directives (ADs) and a patient-directed, online ACP programme) has been shown to increase ACP documentation and patient and clinician empowerment to discuss ACP. Yet, a gap remains in extending PREPARE’s use to surgical populations. We hypothesise that by delivering PREPARE in a patient-facing electronic health record (EHR) centric presurgery workflow for older adults, supported by automated patient reminders and outreach from a healthcare navigator (HCN), we can enable patients and/or surgical teams to engage in ACP discussions.

This is a three-site, single-blinded, pragmatic randomised trial comparing increasing intensity of ACP-focused, patient-facing EHR messaging and HCN support. The outreach occurs prior to a new presurgical clinic visit. We will enrol 6000 patients (2000 each site) aged 65 and older and randomise them equally to the following study arms: (Arm 1) ACP-related cover letter and PREPARE URL information sent via patient portal and postal mail (includes cover letter, AD and PREPARE pamphlet); (Arm 2) Arm 1 plus reminder message via text or MyChart message and (Arm 3) Arm 2 plus HCN outreach and support. The primary outcome is clinically meaningful ACP documentation in the EHR (ie, surrogate designation, documented discussions and ADs) within 6 months of the new surgical visit. The rate of ACP documentation will be compared between treatment groups using generalised estimating equations. Secondary outcomes include a validated four-item ACP engagement survey, administered 2 weeks after the presurgical visit and 6 months later. All analyses will follow the intention-to-treat principle and recent Consolidated Standards of Reporting Trials guidelines.

The study will be conducted according to the Declaration of Helsinki, Protection of Human Volunteers (21 Code of Federal Regulations (CFR) 50), Institutional Review Boards (21 CFR 56) and Obligations of Clinical Investigators (21 CFR 312). The protocol and consent form were reviewed and approved by Advarra, an National Insitutes of Health (NIH)-approved, commercial, centralised Institutional Review Board (IRB). The IRB/Independent Ethics Committee of each participating centre reviewed and approved the protocol and consent and obtained reliance agreements with Advarra prior to study initiation. The study is guided by input from patient and clinical advisory boards and a data safety monitoring board. The results of the study will be disseminated to both academic and community stakeholders, complying with all applicable privacy laws.

ClinicalTrials.gov ID: NCT06090552.

Advarra Pro 00070994.

23-38948.

Protocol Date: 24 October 2024. Protocol Version: 4.

Although low-density lipoprotein cholesterol (LDL-C) is established as the primary cardiovascular disease (CVD) risk factor, some individuals with LDL-C within desirable limits still develop coronary artery disease (CAD). Lipoprotein(a) (Lp(a)) has emerged as a genetically determined independent risk factor for CVD. This study aims to investigate Lp(a) by determining its association with coronary artery stenosis severity, identifying its ethnic-specific genetic determinants and assessing its relationship with an energy-dense dietary pattern.

The PUTRA-CV study is a 3-year, multicentre, case-control observational study involving adult patients who have undergone coronary angiography. The primary outcome is the association between Lp(a) levels and the severity of angiographic CAD (assessed by Gensini or Syntax score). Secondary outcomes include the frequencies of Lp(a)-associated single nucleotide polymorphisms (SNPs) (rs10455872 and rs3798220) and the association between dietary patterns and Lp(a) levels. Lp(a) will be measured using a particle-enhanced immunoturbidimetric method, and SNPs will be genotyped using high-resolution melting. Dietary intake will be assessed using a validated semiquantitative food frequency questionnaire. Data will be analysed using SPSS. Descriptive statistics will be used to summarise population characteristics. Bivariate analyses will use chi-square (2), independent t-tests or Mann-Whitney U tests as appropriate. The independent association between Lp(a) and coronary artery stenosis severity will be determined using multivariable logistic regression, adjusting for confounders. Empirically driven dietary patterns will be derived using reduced rank regression, and their association with Lp(a) will be assessed. For genetic analysis, allele frequencies of the LPA SNPs rs10455872 and rs3798220 will be calculated and compared between cases and controls.

Ethical approval has been obtained from the ethics committees of the Ministry of Health Malaysia (NMRR ID-24-00877-2ID-IIR), Universiti Putra Malaysia (JKEUPM-2024–246), Universiti Teknologi MARA (REC/07/2024-OT/FB/2) and Universiti Malaya Medical Centre (MREC ID NO: 2 02 453–13692). The findings will be disseminated via peer-reviewed journals and conferences.

The COVID-19 pandemic disrupted maternal healthcare access globally, leading many women to give birth outside of healthcare facilities, often assisted by traditional birth attendants (TBAs). This study explored the experiences of Kenyan women who gave birth outside of healthcare facilities during the COVID-19 pandemic based on the Person-Centered Maternity Care (PCMC) framework.

This study used data from descriptive qualitative indepth interviews with Kenyan women who gave birth outside of healthcare facilities between March and November 2020. Participants lived within the catchment areas of six health facilities in Kiambu and Nairobi counties and were recruited by community leaders and community health workers. Interviews were conducted in 2020 via phone and inductively coded and analysed by a team of researchers.

A total of 28 Kenyan women who gave birth outside of healthcare facilities between March and November 2020 completed indepth interviews.

In this sample, approximately one-third of women were assisted by TBAs, while the majority were supported by friends and family members. Women generally described salient aspects of their care pertaining to the PCMC domain of supportive care. During labour, birth and the immediate postpartum, women received emotional support, basic medical assistance and instrumental support such as preparing food and baths. However, women also described concerns about giving birth outside of healthcare facilities, including poor hygiene and lack of privacy in birthing spaces as well as instances of verbal and physical harassment by TBAs. Overall, women worried about potential complications during birth, and many women delayed seeking postpartum and postnatal care.

Women who were unable to access healthcare facilities during the COVID-19 pandemic relied on TBAs and/or friends and family for support during labour and birth. These women faced gaps in PCMC, specifically related to supportive care. Given that birthing outside of healthcare facilities remains common globally, particularly during emergencies such as pandemics, TBAs should be supported to provide more person-centred care to women giving birth outside of healthcare facilities.