Loneliness and social isolation are critical public health issues linked to significant adverse health outcomes and increased healthcare utilisation, including visits to the emergency department (ED). The ED often serves as a primary societal safety net, providing care for vulnerable populations who may be disproportionately affected by these conditions. In fact, loneliness and social isolation might be the underlying reasons they presented to the ED in the first place either consciously or not. For such individuals, the ED encounter may represent a rare point of human contact, yet the stressful and depersonalising nature of the ED environment may paradoxically exacerbate their sense of isolation. Furthermore, ED staff may lack the training and awareness of the scope of the problem to properly screen for loneliness and address it. Yet, the compounded impact of the ED experience on lonely or socially isolated patients and the relationship between loneliness and healthcare utilisation remains poorly understood. This paper presents a protocol for a scoping review designed to systematically map the existing evidence on the experiences of these patients and the perspectives of the clinicians who care for them.

This scoping review will be conducted following the Arksey and O’Malley methodological framework in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The findings will be reported according to the Extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews (PRISMA-S; see ). A comprehensive search will be performed across five electronic databases (PubMed, Embase, Scopus, Web of Science, CNKI) and grey literature sources. Studies published in English or Chinese that address loneliness or social isolation in the ED context, from the perspective of adult or paediatric patients or clinical staff, will be included. A novel, artificial intelligence (AI)-assisted screening process will be utilised for initial relevance assessment, followed by full manual screening and data extraction by two independent reviewers to ensure rigour and mitigate bias. Findings will be synthesised using a narrative approach and thematic analysis to identify key concepts, themes and existing gaps in the literature.

As this study synthesises data from previously published literature, it does not require formal ethical approval. The findings will be disseminated through a manuscript submitted to a peer-reviewed, open-access journal. The aim is to provide an evidence-based roadmap to guide future research, inform policy and support the development of interventions designed to improve care and outcomes for this vulnerable population within the acute care setting.

The review has been registered at Open Science Framework, DOI 10.17605/OSF.IO/MBVSR.

Iron-folic acid (IFA) supplementation in pregnancy is recommended by the WHO, with a dose of 60 mg of iron in contexts where anaemia remains a severe public health problem. Iron-containing supplements may cause side effects that affect acceptability and adherence in a dose-response manner. Maternal multiple micronutrient supplements (MMS), which include iron and folic acid plus additional micronutrients, are also recommended in the context of rigorous research, and programmes are considering transitioning from IFA to MMS containing 30 mg of iron. We will evaluate the effect of iron dose in MMS on maternal acceptability, side effects, adherence and preferences.

The Multiple Micronutrient Supplementation (MMS) Iron Dose Acceptability Crossover Trial is an individually randomised, quadruple-blind, non-inferiority crossover trial of daily antenatal MMS supplementation formulations that contain 60 mg, 45 mg and 30 mg elemental iron among pregnant women in Dar es Salaam, Tanzania. A total of 156 pregnant participants will be randomised to a sequence in which they receive each of the three MMS formulations for 1 month. Participants, investigators, outcome assessors and data analysts will be blinded to the treatment sequence. The primary trial outcome is participant-reported acceptability of each MMS formulation, measured on a Likert scale. Secondary and tertiary outcomes include preferred and least preferred formulation, identification of MMS formulation, reported side effects and adherence assessed by pill count. Regression analyses will be used to assess differences between formulations and will account for sequence and period effects of the crossover trial design. Qualitative in-depth interviews from a subsample of participants will be conducted to understand women’s perceptions and experiences taking the different MMS formulations.

The trial protocol was approved by Harvard T. H. Chan School of Public Health Institutional Review Board (IRB), the Ifakara Health Institute IRB, the Muhimbili University of Health and Allied Sciences IRB, the National Health Research Ethics Sub-Committee and the Tanzania Medicine and Medical Device Authority. Results will be shared through publications and presentations at the local, regional and international levels.

ClinicalTrials.gov Identifier: NCT06069869.

In the first 2 years of the COVID-19 pandemic, Hong Kong adopted strict public health and social measures to stop community transmission of SARS-CoV-2. These include border screening and control, isolation of cases and quarantine of their contacts and universal masking. During this period, attack rates in Hong Kong were among the lowest globally.

To estimate the seroprevalence of COVID-19 among healthcare workers (HCWs) in Hong Kong in 2020 and 2021.

We reviewed contact tracing data from the Hong Kong Department of Health to identify COVID-19 cases reported among HCWs. Between June 2020 and December 2021, we conducted a longitudinal cohort study to estimate the seroprevalence of COVID-19 among HCWs working in hospitals and clinics in Hong Kong during the first 2 years of the COVID-19 pandemic.

Overall seropositivity of COVID-19 by plaque reduction neutralisation test during the first (May–October 2020) and second round (November 2020–April 2021) of the study was 0% (95% CI 0.00% to 0.49%) and 0.52% (95% CI 0.14% to 1.33%). After COVID-19 vaccines were offered to HCWs in February 2021, seroprevalence by surrogate virus neutralisation assay among cohort participants who provided biannual blood samples rose to 68.7% (95% CI 65.9%, 71.3%) and 80.2% (95% CI 76.8%, 83.2%) in round 3 (May–October 2021) and the first 2 months of round 4 (November–December 2021).

Seroprevalence in Hong Kong HCWs in our study was low despite considerable exposure to confirmed COVID-19 cases in some study participants. However, the low rate of community transmission may have also contributed to the observed low seroprevalence among HCWs in our cohort.

Despite the minimally invasive nature of video-assisted thoracoscopic surgery (VATS), moderate-to-severe postoperative pain remains frequent and impairs recovery. Intravenous lidocaine possesses multimodal analgesic, antihyperalgesic and anti-inflammatory properties that may improve pain control and functional outcomes, but robust evidence in thoracic surgery is lacking. Moreover, its potential to attenuate neuropathic pain, a key component of chronic post-thoracic pain syndromes, has not been adequately investigated. This trial will determine whether continuous perioperative intravenous lidocaine infusion improves recovery, reduces acute pain intensity and prevents the development of neuropathic pain after VATS.

This single-centre, randomised, double-blind, placebo-controlled trial will enrol 84 adult patients undergoing elective VATS. Participants will be randomised (1:1) to receive either intravenous lidocaine (bolus 1 mg/kg at induction followed by continuous infusion at 1.5 mg/kg/hour intraoperatively and postoperatively for 24 hours) or matched normal saline postoperatively, with identical intraoperative management in both groups. The primary outcome is the incidence of moderate-to-severe movement-evoked pain at 24 hours postoperatively. Secondary outcomes include pain at 48 and 72 hours, opioid consumption, pulmonary complications, sleep quality, quality of recovery, neurocognitive outcomes and chronic neuropathic pain at 3 months. Analyses will follow the intention-to-treat principle.

The study protocol was approved by the Institutional Review Board of Tongji Hospital (Reference No. TJ-IRB202509102) and registered in the Chinese Clinical Trial Registry (ChiCTR2500111163). Written informed consent will be obtained from all participants. Results will be submitted to peer-reviewed journals and academic conferences.

ChiCTR2500111163.

Individuals with incomplete spinal cord injury (iSCI) often experience impaired balance control and turning-while-walking ability, which increase the risk of falls and limit their community mobility. While overground exoskeleton training has shown promise in improving gait and balance, evidence from randomised controlled trials (RCTs) on ambulation of individuals with iSCI remains limited. This protocol outlines a cluster RCT investigating the effectiveness of overground exoskeleton-assisted gait training compared with conventional training and usual care in improving turning-while-walking performence, balance control, and functional mobility in individuals with iSCI.

This multicentre, cluster RCT will compare 12-week interventions across three groups: (1) overground exoskeleton training group, (2) conventional training group and (3) usual care group. Participants with ambulatory iSCI will be recruited from three centres in Hong Kong SAR and mainland China. Primary outcomes include turning duration and number of steps during a 2-m turning-while-walking test. Secondary outcomes include static and dynamic balance, sensorimotor integration, gait performance, muscle strength, spasticity, quality of life, self-efficacy and fall incidence. Assessments will be conducted at baseline, mid-intervention, postintervention and at the 1-month follow-up.

This study has received approval from the Research Ethics Committees of Hong Kong Metropolitan University, the Affiliated BenQ Hospital of Nanjing Medical University, and Changzhou Sunshine Rehabilitation Hospital. Written informed consent will be obtained from all participants before enrolment. Study findings will be shared through peer-reviewed publications, conference presentations and summaries available to participants upon request.

NCT06971510.

Methotrexate (MTX) effectively controls rheumatoid arthritis (RA) but often leads to side effects (SE) such as gastrointestinal (GI) issues, liver toxicity and bone marrow suppression. To develop clinically interpretable machine learning (ML) models that accurately predict MTX-related SE in patients with RA taking MTX. The aim was to enhance predictive accuracy and to identify patient-specific risk factors using explainable artificial intelligence (XAI), thereby enabling transparent clinical interpretation. We specifically sought to address the unmet need for individualised risk stratification using real-world, multicentre observational data.

Retrospective case-control study.

Across 23 rheumatology clinics in South Korea, based on data from a nationwide multicentre cohort.

A total of 5077 patients with RA were initially enrolled from the Korean Observational Study Network for Arthritis. After excluding those with missing clinical, demographic or prescription data and those not receiving MTX, 2375 patients remained eligible. Among these, 1654 and 1218 patients were included in the overall SE and GI SE analysis groups, respectively, after 1:1 propensity score matching. All patients were aged ≥18 years and met the 1987 American College of Rheumatology classification criteria.

The primary outcome was the presence of SE in patients with RA taking MTX, categorised into overall SE and GI SE, based on standardised patient questionnaires and clinical assessments. The secondary outcome was the identification of key predictors using SHapley Additive exPlanations (SHAP) to enhance the interpretability of ML predictions.

Among six ML classifiers, extreme gradient boosting demonstrated the highest performance in predicting overall SE (area under the curve (AUC) 0.781, F1 score 0.672, area under the precision-recall curve (AUPRC) 0.757) and GI SE (AUC 0.701, F1 score 0.690, AUPRC 0.670). SHAP analysis identified key predictive features including age, physician visual analogue scale score, alanine aminotransferase, Health Assessment Questionnaire score, celecoxib use and drug adherence. Logistic regression confirmed statistical significance for multiple variables (eg, OR 4.63; 95% CI 1.41 to 20.90 for non-adherence >30 days; OR 1.45; 95% CI 1.14 to 1.85 for celecoxib use). DeLong’s test indicated that boosting models significantly outperformed support vector machine (p

Interpretable ML models using real-world clinical data can accurately predict SE in patients with RA taking MTX. These models may facilitate early identification of high-risk individuals and inform personalised treatment strategies. Integration into clinical decision support systems could improve MTX safety monitoring. Further prospective validation in external cohorts is warranted.

Neutropenic fever (NF) has a crude mortality rate of 3–18%. International guidelines recommend that all patients with NF receive ultrabroad-spectrum antibiotics (UBSAs) within 1 hour of emergency department (ED) registration. However, over 70% patients presenting to hospital with suspected NF (sNF) cannot access absolute neutrophil count (ANC) result within 1 hour, do not have NF and do not require UBSAs. In ED and hospitalised patients with sNF, we hypothesise that the ASTERIC protocol effectively and safely reduces the use of UBSAs compared with standard care alone.

This pragmatic, parallel, multicentre, type 1, hybrid effectiveness-implementation, stepped-wedge, before-and-after, cluster randomised controlled trial aims to evaluate whether antibiotic prescribing can be safely reduced through implementing a multifaceted antibiotic stewardship intervention (ASTERIC) in adult patients with sNF presenting to EDs. The sNF was defined as a fever with a single oral temperature of ≥38.3°C (101°F) within 24 hours before ED registration or a temperature of ≥38.0°C (100.4°F) sustained over a 1-hour period, following last chemotherapy or targeted therapy within 6 weeks for any solid tumour, or in any period following therapies against leucaemia, lymphoma, myelodysplastic syndrome, aplastic anaemia, multiple myeloma or recipient of HSCT. The study will involve eight hospitals in Hong Kong with variable baseline practice. We will include 704 adult patients (352 patients in pre-implementation and post-implementation periods, respectively) with sNF (tympanic temperature ≥38.3°C) and 48 staff participants (6 staff participants in each hospital). Healthcare professionals will receive a multifaceted stewardship intervention consisting of risk assessment tools, fast-track ANCs, a decision tool for patient management and antibiotic use, supported by an educational package and staff interaction programmes (ASTERIC protocol). Patients’ blood ANC, and cancer therapy and chronic illness therapy scores will be measured. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) and Proctor conceptual frameworks will be followed for evaluation of implementation. The main outcome measures are the mean total dose of UBSAs prescribed in 7 days and serious adverse events at 30 days. Data analysis will incorporate intention-to-treat, per-protocol and as-treated analyses for service outcomes (effectiveness, safety, quality of life assessments and cost-effectiveness) and mixed methods for implementation outcomes, informed by the Theoretical Domains Framework. We expect that the study results will inform health policy with improvement in hospital services in treating stable sNF, evidenced by improved safe antibiotic stewardship, early antibiotic de-escalation and reduced costs and length of stay.

The institutional review boards of all study sites approved this study. This study will establish the ASTERIC protocol safely improves antibiotic stewardship and clinical management in adult patients with sNF. We will disseminate the findings through peer-reviewed publications, conference presentations and educational activities. All patients with sNF will be influenced by the new protocol which is agreed at hospital level. Randomisation is at hospital level, not patient level. Patient consent is sought for follow-up and data access, not for treatment. Staff consent is sought for interviewing.

NCT06794320.

To examine the geospatial distribution of gestational diabetes mellitus (GDM) over time in Australia.

An ecological study was conducted using data from the National Diabetes Services Scheme (GDM cases). Data at Statistical Area Level 2 (SA2) level, a medium-sized spatial unit, on population denominators (women who gave birth) were obtained from the Australian Bureau of Statistics. The spatiotemporal distribution of GDM was explored at the SA2 level over three periods: 2016–2017, 2018–2019 and 2020–2021. Hotspot and cluster analyses were undertaken using Getis-Ord Gi* and local Moran’s I statistics.

A nationwide study in Australia was conducted between 2016 and 2021.

Women diagnosed with GDM and those who gave birth were included.

Age-standardised and crude incidence of GDM per SA2.

During 2016–2021, 1 718 963 eligible women who gave birth in Australia were included. Hotspot areas of GDM were consistently observed in Victoria (Southwest and North Melbourne); Western Australia (South and Southwest Perth); Australian Capital Territory (ACT) (East and North Canberra); Queensland (North Brisbane) and New South Wales (West and Southwest Sydney and Southeast New South Wales). ACT (South Canberra), North Tasmania, Northern Territory (North Darwin) and Victoria (South East Melbourne) had new hotspot regions recorded in the last two consecutive study periods.

GDM incidence varies by geographical area over time, with hotspots in specific regions suggesting the need for geographically targeted policy interventions to curb the growing burden of GDM.

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.

Palliative cancer care is comprehensive, specialised medical care of patients that aims to alleviate physical, mental and emotional distress based on patients’ needs rather than on prognosis. In Ethiopia, the federal ministry of health started palliative care (PC) in 2016. Since then, services have been developed and integrated as important components of the Health Sector Transformation Plan II. However, there is a scarcity of nationally summarised data regarding PC service utilisation in Ethiopia. Therefore, this protocol describes a planned systematic review and meta-analysis that will evaluate utilisation of PC services and its predictors among adult cancer patients in Ethiopia.

The online databases of PubMed, Hinari, EMBASE, CINHAL, Science Direct, Scopus and Google Scholar will be comprehensively searched from inception to 31 February 2025. To assess the quality of included studies, the Joanna Briggs Institute critical appraisal tools will be used. The statistical software STATA V.17 will be used for data analyses. To examine the heterogeneity between studies, inverse variance (I²) will be used. To calculate the pooled prevalence of PC service utilisation, a fixed or random effects meta-analyses model will be used with a 95% CI, depending on the presence or absence of heterogeneity between included studies. To look for publication bias, a visual inspection of the funnel plot and Egger and Begg’s regression test and a 5% level of significance will be used.

Ethical approval is not applicable. The results will be disseminated to academic beneficiaries and the public.

Dysarthria is one of the most prevalent communication disorders following a stroke, and it can lead to social isolation and depression, significantly hindering rehabilitation progress. Recent studies suggest that acoustic startle priming (ASP) tasks may enhance speech performance and motor initiation through the corticoreticulospinal tract. This has opened up new possibilities for the application of ASP in the rehabilitation of poststroke dysarthria. The aim of this study is to investigate whether ASP can improve rehabilitation outcomes in individuals with poststroke dysarthria.

This prospective, randomised, controlled clinical trial plans to enrol 48 participants diagnosed with poststroke dysarthria. Participants will be randomly assigned to either the ASP group (n=24) or the control group (n=24). Both groups will undergo 30 min of standard dysarthria rehabilitation training daily, 5 days per week for 2 weeks. The ASP group will receive an additional 30 min articulation training with ASP, while the control group will receive an equivalent 30 min articulation training with normal acoustic stimuli. Speech and voice characteristics will be assessed using Frenchay Dysarthria Assessment, PRAAT software at baseline, 1 week and 2 weeks postintervention. Furthermore, Functional Near Infrared Spectroscopy will be employed during ASP tasks to investigate cortical activation and changes in brain network connectivity.

The study has been approved by the Tongji Hospital Medical Ethics Committee (TJ-IRB202312100). Raw data from this trial will be publicly available on the Public Management Platform for Clinical Research. The findings will be disseminated through international conferences and peer-reviewed journals.

ChiCTR2400081279.

During the COVID-19 pandemic, a substantial decrease was observed in hospital admissions and in-hospital procedures for patients with acute cardiovascular diseases (CVDs). The extent to which measures to prevent COVID-19 transmission, for example, lockdowns, affected the outpatient care of patients at higher cardiovascular risk remains unclear. We aimed to compare outpatient department (OPD) attendance, cardiovascular risk management (CVRM) and cardiovascular health (CVH) of patients at higher cardiovascular risk referred to an OPD of a tertiary care centre between preCOVID-19, during and postCOVID-19 periods.

We included all adult patients at higher cardiovascular risk referred to the cardiology, vascular medicine, diabetology, geriatrics, nephrology or multidisciplinary vascular surgery OPDs of the University Medical Centre Utrecht, the Netherlands, between March 2019 and December 2022, in a prospective cohort study.

We assessed trends in the number of first and follow-up appointments and in the completeness of extractable CVRM indicators from the electronic health record (EHR) as a proxy for CVRM guideline adherence. CVH was determined using the Life’s Essential 8 metric (score 0–100, the higher score, the better). We investigated whether CVH differed between COVID-19 periods compared with the reference period (ie, 2019) and stratified by OPDs, using multivariable linear regression, adjusted for age, gender, CVD history and whether the patient had a previous appointment before the reference period.

Among 15 143 patients, we observed a 33% reduction in the weekly number of first appointments during the COVID-19 pandemic, with the largest reductions in the cardiology and nephrology OPDs, with no differences between women and men. Follow-up appointments conducted remotely, compared with before the COVID-19 pandemic, increased significantly for all OPDs. CVRM indicators were up to 11% less extractable during the first lockdown yet returned to prepandemic levels directly after the first lockdown period. The CVH score of patients visiting the nephrology, vascular medicine and geriatrics OPDs during the first lockdown was 11.23 (95% CI 2.74 to 19.72), 5.68 (95% CI 0.82 to 10.54) and 5.66 (95% CI 0.01 to 11.31) points higher, respectively, compared with the prepandemic period. In between the second and third lockdowns, the CVH score was comparable to the preCOVID reference period, yet for the cardiology OPD it was significantly higher (5.54, 95% CI 2.04 to 9.05).

During the COVID-19 pandemic, weekly numbers of first appointments to OPDs decreased, and a population with a higher CVH score (ie, better CVH) visited certain OPDs, especially during the first lockdown period. These suggest that patients with poorer CVH more often avoided or were unable to visit OPDs, which might have resulted in missed opportunities to control cardiovascular risk factors and potentially may have led to preventable disease outcomes. For future epidemics and pandemics, it seems vital to develop a strategy that includes an emphasis on seeking healthcare when needed, with specific attention to patients at higher CVD risk.

Gastroenteropancreatic neuroendocrine tumours (GEP NET) are malignant neoplasms that impact survival. Somatostatin analogues (SSA) are used for treating hormonal symptoms caused by GEP NET and have antiproliferative effects. They are used as first-line therapy in patients with advanced GEP NET, but disease control is limited to a median progression-free survival (mPFS) of 14–32 months. Second-line treatment options include targeted therapy (everolimus or sunitinib), or peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATATE. In patients suffering from a NET-related hormonal syndrome, SSA is generally continued life-long. However, there is no consensus on whether it is beneficial to continue SSA in non-functional NET upon disease progression. Due to the ongoing activity of the somatostatin receptor pathway in GEP NET progressing on first-line SSA, we hypothesise that SSA have an added efficacy in second-line therapy.

The SAUNA trial is an international, multicentre, open-label, randomised, controlled, pragmatic clinical trial. 270 patients with advanced, non-functional GEP NET and progression under first-line SSA will be included in substudy 1 (PRRT; n=142) or substudy 2 (targeted therapy (everolimus/sunitinib); n=128) per investigator’s choice of second-line therapy and will be randomised (1:1) per substudy between SSA continuation or SSA withdrawal arms. Co-primary endpoints are the difference in progression-free survival (PFS) according to the RECIST (Response Evaluation Criteria In Solid Tumours) V.1.1 criteria and difference in time to deterioration (TTD) in quality of life (QoL) per substudy after initiating second-line therapy with or without SSA. Secondary endpoints include the PFS rate at 18 months, the difference in pooled PFS and TTD combining both substudies, overall survival, response rates, QoL, costs, cost-effectiveness and toxicity. The study design was developed in cooperation with the Belgium and Dutch patient organisations.

The study has been approved on 31 May 2023 by the Ethical Committees and Regulatory Authorities of the concerned member states (EU CT number 2022-502703-30-00). Both the trial management group and the steering committee will oversee good governance of this trial. Results of the study will be published in peer-reviewed international journals and presented at international conferences.

NCT05701241.