Exercise therapy is the most recommended treatment for chronic low back pain (LBP), with evidence supporting modest effects, likely due to the heterogeneity of patient presentations. Evidence suggests that matching individuals to the most appropriate exercise type could improve outcomes. Systematic reviews also emphasise that effective exercise interventions should be patient centred, target paraspinal muscle health and be of sufficient duration. This study addresses these gaps using a targeted care approach to identify a homogenous sample that is more likely to respond to our interventions. The inclusion of a sample with predominant nociceptive pain profile will be performed with the integration of the Pain and Disability Drivers Management Model (PDDM) and the Lumbar Spine Instability Questionnaire (LSIQ). The primary aim of this two-arm randomised controlled trial is to compare the effectiveness of motor control plus isolated lumbar extension exercises (MC+ILEX, arm 1) to free-weight resistance training (arm 2) in reducing LBP-related disability. Secondary aims include examining whether changes in multifidus composition mediate disability improvements comparing intervention effects on muscle size and quality, strength, mobility, pain, quality of life, sleep, physical activity and satisfaction; exploring baseline LSIQ scores and sex/gender as moderators of treatment response; and investigating participants’ perceptions and experiences of exercise therapy.

A total of 106 participants will be recruited through primary and secondary care and randomised (1:1) to receive either MC+ILEX or free-weight resistance training. Both groups will complete 48 exercise sessions over 16 weeks. The primary outcome will be disability at 16 weeks, measured by the Oswestry Disability Index. Secondary outcomes include multifidus muscle composition and size, lumbar and gluteal muscle strength, hip range of motion, pain, physical and mental function, satisfaction and recovery, health-related quality of life, sleep quality and physical activity levels. Linear mixed-effects models will be used to assess primary and secondary outcomes. Regression analyses will explore whether baseline LSIQ scores moderate treatment effects on multifidus composition and other outcomes. A subsample of participants will undergo semistructured interviews before and after the intervention to explore their illness perceptions, illness mindsets, perceptions of exercise therapy, as well as their experiences and satisfaction with the two exercise interventions. Reflexive thematic analysis will be used to analyse qualitative data.

This study received ethics approval from the Central Ethics Research Committee of the Quebec Minister of Health and Social Services (CCER-25-26-14). Results will be submitted to peer-reviewed journals and scientific meetings.

ISRCTN14864451.

Current expert consensus statements generally suggest cardiovascular risk assessment, including atrial fibrillation (AF) screening, on detection of covert brain infarctions (CBIs). However, evidence to guide management of CBI remains limited. In the absence of randomised clinical trials specifically targeting CBI populations, observational studies comparing individuals with and without CBI can provide insights into the prevalence and burden of cardiovascular risk factors.

We aimed to compare the burden of atherosclerosis and cardiovascular risk factors in participants with CBI to those without, and to explore the yield of AF screening in individuals with CBI.

A prospective population-based birth cohort study including men and women born in 1950 and resident in Akershus County, Norway.

The two hospitals serving the population of Akershus county, Norway.

Participants included in the Akershus Cardiac Examination (ACE) 1950 study who also underwent a subsequent MRI examination were eligible for this study.

Cardiovascular risk assessment was performed at study inclusion (2012–2015). Carotid ultrasound was used to quantify atherosclerosis through a carotid plaque score, and CHA₂DS₂-VA and Systematic COronary Risk Evaluation 2 (SCORE2) scores were calculated to estimate cardiovascular risk. Brain MRI was performed in a randomly selected, blood pressure-stratified subset of participants (2016–2024). CBI was defined as focal lesions consistent with ischaemia in the absence of clinical stroke. Participants with CBI were offered 72-hour ambulatory ECG monitoring for AF detection.

MRI was performed in 414 of 3706 (11%) participants in the ACE 1950 Study. The mean age at the time of the MRI examination was 70.2±2.3 years, and 165 (41%) were women. CBI was identified in 54 participants (13%), of whom 45 (83%) completed 72-hour ambulatory ECG monitoring. There were no differences in mean carotid plaque score, SCORE2 or CHA₂DS₂-VA score between participants with CBI compared with those with normal MRI findings. AF was detected in one (2%) participant with CBI.

In this community-based cohort of individuals in late midlife, individuals with CBI did not have an increased cardiovascular risk compared with those without, as indicated by SCORE2, CHA₂DS₂-VA score, age-appropriate carotid plaque burden and a low prevalence of AF.

URL: https://www.clinicaltrials.gov. Unique identifier: NCT01555411.

To assess whether a medical telephone helpline and the use of a computer-assisted structured triage tool led to a reduction in demand for acute and emergency care in hospital emergency departments (EDs) or other ambulatory out-of-hour (OOH) services.

We conducted an ecological study using secondary data on outpatient care.

The study was conducted in 10 out of 16 federal states of Germany.

The analysis was based on ambulatory claims data for the years 2016–2020 by 11 Associations of Statutory Health Insurance Physicians (ASHIPs) covering more than 64% of the total German population.

The evaluated intervention comprised two components. The first was the introduction of a 24/7 medical helpline (116117), established to assist individuals with medical concerns in accessing appropriate care. The second component was the introduction of the computer-assisted triage tool SmED (Strukturierte medizinische Ersteinschätzung in Deutschland, Structured medical initial assessment in Germany) to support call-takers by suggesting medically relevant questions to identify red flags and determine the urgency of treatment and a possible treatment facility. For the analysis, approximately 3 years before and 1 1/2 years during the intervention were considered.

Main outcome was the effect on acute and emergency care which was measured as the number of personal doctor-patient contacts (1) in EDs (ED cases, data of 10 ASHIPs could be considered) and (2) in EDs or other OOH services (ED and OOH cases, data of 11 ASHIPs could be considered).

The analysis was limited by legal changes mandating intervention components across all study sites—leading to a loss of control groups and delayed implementation—and the onset of the COVID-19 pandemic. Across all ASHIPs and counties, the number of calls to 116117 and the number of SmED assessments showed a negative association with the number of ED cases (total change: 295.0 cases to 224.5 cases per 100 000 inhabitants, 116117 calls: r=–0.04; 95% CI –0.04 to –0.035; p≤0.001, SmED: r=–0.15; 95% CI –0.35 to 0.05; p=0.138) as well as with the combined number of ED and OOH cases (total change: 516.4 cases to 400.3 cases per 100 000 inhabitants, 116117 calls: r=–0.02; 95% CI –0.03 to –0.001; p≤0.01, SmED: r=–0.58; 95% CI –0.98 to –0.19; p≤0.01). However, the association between the number of SmED assessments and ED cases was not statistically significant. Moreover, the magnitude and direction of effects varied across ASHIPs. Sensitivity analyses restricted to time periods preceding the onset of the COVID-19 pandemic showed a non-significant negative association for 116117 calls and a significant positive association for SmED assessments with both ED cases and combined ED and OOH cases (ED cases: 116117 calls: r=–0.001; 95% CI –0.019 to –0.018; p=0.928; SmED: r=0.37; 95% CI 0.29 to 0.45; p≤0.001; ED and OOH services cases: 116117 calls: r=–0.03; 95% CI –0.06 to 0.003; p=0.077; SmED: r=0.34; 95% CI 0.20 to 0.48; p≤0.001).

Our findings indicate a trend suggesting that implementation of a 24/7 medical helpline may reduce the demand for acute and emergency care at EDs and OOH services, although clear evidence is lacking. The impact of SmED use remains inconclusive. Further research should ideally incorporate data linkage and controls and assess the effectiveness and efficiency of the triage process, as well as the quality of subsequent care at the individual level.

Risk reduction training for UK care home staff is limited, not standardised and challenging to implement. Virtual reality (VR) is an immersive, engaging method of education delivery that is being adopted in health and social care. VR may be an effective education tool in care homes, but this research has yet to be conducted.

The VR-CARE project aims to create a new VR risk reduction training programme for care homes that combines hand hygiene and falls prevention modules, and to evaluate this through a pilot trial to inform a future randomised controlled trial (RCT).

There are two research phases with patient and public involvement and engagement (PPIE) activities embedded throughout. Care home stakeholders are collaborating to design the training and toolkit, oversee methods, review resources for accessibility, support recruitment and ensure the project meets the needs of the workforce and positively impacts resident care.

In phase 1, we will use a mixed-methods and user-centred design approach to develop the VR training and an accompanying implementation toolkit needed to deliver it. The training will be developed and tested by 15 care home staff across three rounds to identify and inform changes that maximise usability and acceptability. We will conduct up to 20 interviews with staff from VR companies and care homes to support toolkit development.

Phase 2 is a mixed-methods pilot cluster RCT, with a waitlist control and process evaluation with up to 80 unregistered staff members from six North England care homes, to develop the measures and methods to inform a future trial. The process evaluation will generate knowledge about VR as a training mechanism in care homes. This phase will focus on the practicality of using VR, broader impacts (eg, on residents), contextual considerations and how it might be scaled up.

The University of Manchester Proportionate University Research Ethics Committee has approved phase 1 (Reference: 2025-24416-44642). We will obtain further approval before commencing phase 2.

Outputs will include user-friendly and acceptable VR risk reduction training for care homes, accompanied by an implementation toolkit adaptable for other VR training in social care settings. Materials (eg, training overviews, infographics and videos) will be developed to support uptake. Findings will be presented at conferences and published in journals. Lay summaries will be co-created with our PPIE group, and additional dissemination methods will be co-developed to broaden reach.

HIV/sexually transmitted infection (STI) prevention interventions are only modestly successful among youth, particularly for young people of colour and sexual and gender minority (SGM) youth. Even among disparate intervention modalities delivered with high fidelity, differences between intervention types have been minimal. One consistent theme has emerged: the role of the youth:provider relationship in predicting intervention response. In line with calls for examination of relational factors, the next essential step is a harmonised analysis to evaluate connections between the youth:provider relationship and co-occurrence of alcohol and cannabis use, in youth HIV/STI prevention intervention response.

Our team has completed six sizeable HIV/STI behavioural prevention studies, generating n=1136 independent youth (baseline M_age=17, range=13–24; 43% female; 21% SGM; 54% Hispanic; 9% African American; 7% Native American/Alaska Native) who received prevention programming and were followed at 1-, 3-, 6-, and/or 12 months. We will harmonise these studies and build a longitudinal mixed-effects machine learning model, with youth:provider relationship as a predictor of intervention response. Participant factors, provider factors and their interaction will be included in the model. Given high rates of alcohol and cannabis comorbidity, we will also examine syndemic outcomes (co-occurring HIV/STI risk behaviours, alcohol use and cannabis use). These data are crucial to informing next step HIV/STI and syndemic intervention programming with this age group.

This secondary analysis study is exempt from human subjects regulations under category 4(iii) as determined by the Institutional Review Board at UConn Health. Results will be disseminated via presentations at annual scientific conferences, submissions to peer-reviewed journals, to mental health and substance use providers, as well as community programmes for youth at high risk for HIV/STI and substance use.

Healthcare utilisation (HU) is key to improving the health of residents in urban informal settlements. This study aimed to explore household-level factors influencing HU among informal settlement households in Freetown, Sierra Leone.

Cross-sectional survey.

Three informal settlements (Cockle Bay, Dwarzark and Moyiba) in Freetown, Sierra Leone.

Primary data from 4871 households were collected during the Health and Wellbeing survey conducted between April and May 2023, targeting households with adults aged 18 years and older.

The primary outcomes were households HU both within and outside informal settlements. Household-level predisposing and enabling explanatory variables were derived from Andersen’s Behavioural Model of HU.

Disability in households increases HU within settlements (especially in Dwarzark, 13% and Moyiba, 10%) but is less likely outside. Households engaged in income-generating activities are more likely to seek healthcare within settlements, but 12% less likely outside in Cockle Bay and Dwarzark. Food insecurity decreases HU within Dwarzark (9%) and increases HU outside by 174% in Moyiba. Longer water fetching times and water shortages were associated with higher HU (between 6% and 16%) within settlements, especially in Cockle Bay and Dwarzark. Clean water sources (eg, piped dwelling, bowser, surface, bottled) were consistently associated with higher HU both within and outside settlements. Shared sanitation facilities (such as shared toilets) were positively associated with HU both within and outside settlements, particularly in Dwarzark and Moyiba. Households with income from fishing, informal salaried work and bike riding showed higher HU both within and outside settlements, especially in Dwarzark and Moyiba.

We identified strong settlement-specific patterns of household-level factors that influence HU both within and outside Freetown’s informal settlements. These findings provide a foundation for developing targeted policies such as strengthening local services, addressing affordability and accessibility barriers and supporting vulnerable occupation groups.

To study the factors that influence physicians’ and patients’ use of, and willingness to use, economic information in clinical decision-making, and examine physicians’ views on whether clinical practice guidelines can support its use.

Semistructured focus group discussions with an inductive content analysis.

Finnish health centre general practitioners (GPs) and adult patient representatives, five groups of each.

22 GPs and 15 patient representatives.

In the GP groups, five factors involved in using economic information in clinical decisions were raised: the issue of who pays, knowledge about cost information, the cost-benefit ratio of treatments, care planning and health economic understanding. Concerning the inclusion of economic information in clinical guidelines, GPs raised themes including the content and means of presentation of economic information, and advantages and challenges related to the integration of economic information into clinical guidelines. In the patient groups, the identified themes related to seeing the costs of treatments, the organisation of healthcare services, inclusion of cost information in clinical guidelines, patient information and support, and cost containment in healthcare.

The study suggests that GPs and patients are willing to use economic information in clinical decision making. It also implies a need for easily accessible and understandable economic information, and that clinical guidelines may be a good way to support this. In addition, the study highlights the need for education on the economic aspects of healthcare for physicians.

To determine the safety and efficacy of ruxolitinib (RUX) and fostamatinib (FOS) compared with standard of care (SOC) in patients requiring hospital admission for the treatment of COVID-19 pneumonia.

Adaptive multiarm, multistage, randomised, open-label trial (three arm, two stage).

Five hospitals in England between October 2020 and September 2022.

Hospitalised patients (≥18 years) with COVID-19 pneumonia defined by a modified WHO COVID-19 severity grade of 3 or 4.

Participants were randomly assigned 1:1:1 to receive RUX (10 mg two times per day for 7 days then 5 mg two times per day for 7 days), FOS (150 mg two times per day for 7 days then 100 mg two times per day for 7 days) or SOC.

Primary outcome was development of severe COVID-19 pneumonia (modified WHO severity grade≥5) within 14 days of randomisation. Secondary outcomes included mortality, invasive and non-invasive ventilation, venous thromboembolism, duration of hospital stay, readmissions, inflammatory markers and serious adverse events (SAEs).

At stage 1, 181 patients were randomised, with 4 assessed as ineligible post randomisation. FOS was stopped early for futility with 16 participants (27.6%, n=58) developing severe COVID-19 pneumonia compared with 15 (25.0%, n=60) in the SOC arm (adjusted odds ratio (aOR) compared with SOC: 1.12; 95% CI 0.49 to 2.58; p=0.608). RUX progressed to stage 2 but the trial was stopped early due to slow recruitment. At the final analysis, 10 participants (16.1%, n=62) developed severe COVID-19 pneumonia in the RUX arm compared with 15 (24.6%, n=61) in the SOC arm (aOR: 0.63; 95% CI 0.25 to 1.57; p=0.161). Four (7.4%) participants in the FOS arm, none in the RUX arm and three (5.5%) in the SOC arm died within 14 days of randomisation. Infections were the most frequently reported SAE and were numerically higher in the FOS (10, 17.2%) and RUX (10, 16.1%) arms compared with SOC (7, 11.5%). Two unexpected serious adverse reactions occurred in the RUX arm only.

We found no evidence that FOS was superior to SOC for the treatment of COVID-19 pneumonia in patients requiring hospital admission. Due to early stopping, the trial was underpowered to establish RUX’s effect in this population. Further study is needed.

NCT04581954; EUDRA-CT: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001750-22/GB.

Fever is the leading reason for consultation among children in general practice. 20% of febrile children require additional tests to distinguish between viral infections and severe bacterial infections. Point of care capillary C-reactive protein (POC CRP) testing provides on-site results within 5 min but remains underutilised in primary care settings in France. This study will demonstrate how the use of POC CRP could optimise the care pathway for febrile children, saving time for physicians and patients, and making economic savings.

This is a multicentre, prospective, cluster-randomised stepped-wedge trial that will take place from September 2025 to March 2026. The required sample size is estimated at 420 patients. The primary outcome is the difference in referral rates to facilities equipped for emergency laboratory testing (medical biology laboratories, emergency departments) when using POC CRP versus standard care. The study will be conducted in primary care practices and out-of-hours clinics in south France among febrile children aged 3 months to 15 years, over the 6-month viral and bacterial epidemic period. A cost-consequence analysis and a budget impact assessment will also be performed.

The protocol was approved by the Ile de France VII Committee for the Protection of Persons (2024-A02844-43), the French Advisory Board on Medical Research Data Processing and the French Personal Data Protection Authority. The study was prospectively registered on clinicaltrials.gov.

NCT06910631.

The management of active patients with symptomatic knee osteoarthritis (KnOA) who are too young for total knee arthroplasty poses a specific challenge to clinicians. Research studies show that improving quadriceps muscle strength improves pain and function; however, aspects of the disease render it difficult for patients to achieve and maintain improvements. Recombinant human growth hormone (rHGH) is shown to increase the magnitude and duration of muscle growth when combined with exercise treatment in adult populations. Hence, rHGH combined with physical therapy may provide meaningful benefits in the treatment of KnOA.

This is a single-centre, double-blind, randomised trial to pilot a future Phase III trial from 2025 to 2028. Participants are aged 18–60 with clinical and radiographic evidence of isolated degenerative arthritis of the knee (patellofemoral or tibiofemoral). The investigational product is rHGH (Saizen (somatropin of rDNA origin, EMD Serono)) and a saline placebo. Participants will deliver the solution via subcutaneous injection area once per day at a dose of 0.5 mg HGH per body surface area (0.5 mg/m²) for 6 weeks, alongside participation in a lower limb strengthening programme developed by rehabilitation specialists. 17 participants will be recruited into each study arm.

The primary outcomes are feasibility (compliance with the study drug regimen for the 6-week administration period and enrolment rate) and safety (the proportion of minor and major adverse events between groups). The primary endpoint for these outcomes will be at 6 weeks. The secondary outcomes are knee extension strength, knee flexion strength, radiographic arthritis progression, thigh muscle circumference, MRI-measured quadriceps muscle volume and patient-reported outcome measures (Knee Osteoarthritis Outcome Score (KOOS), SF-20 and Tegner). The primary endpoint for these outcomes will be at 12 weeks, and the final endpoint will be 24 months, where final radiographic (X-ray) assessment will take place.

The primary outcome of compliance will be a calculation of mean compliance between groups, which can be analysed as a t-test after the treatment period. A two-sample, two-sided t-test will compare the clinical (secondary) outcome of greatest interest: knee extension strength at baseline versus week 6 compared between treatment groups. Other secondary outcomes will be compared using a simple linear mixed-effects model. The ² test will be used to determine whether the number of participants who made meaningful changes was different between groups. The null hypotheses are that the rHGH and placebo groups will have no difference in compliance rates, safety events, knee extension strength at 12 weeks and arthritis grade progression at 24 months.

This study has been approved by the Sunnybrook Research Institute Research and Ethics Board (#6427) and received a no-objection letter from Health Canada Clinical Trials. The primary sponsor is the Sunnybrook Centre for Clinical Trial Studies (CCTS). The findings of this study will be published in a peer-reviewed journal and presented at orthopaedic conferences.

NCT07036003.

Glucocorticoid therapy is prescribed for a variety of inflammatory conditions and is associated with severe adverse effects. A glucocorticoid withdrawal syndrome (GWS) may occur after prolonged glucocorticoid treatment—with or without biochemical glucocorticoid-induced adrenal insufficiency (GIAI). Previously, GWS was not considered an entity, probably due to the overlap between symptoms of GWS and GIAI. The Addison’s disease-specific quality of life questionnaire (AddiQoL-30) is a validated tool for quantifying symptoms of adrenal insufficiency resembling GWS. In the present study, we test the hypothesis that patients with a low AddiQoL-30 score and/or low cortisol response to a short Synacthen test (SST), after cessation of prednisolone treatment, may benefit from low-dose hydrocortisone therapy without increasing the risk of metabolic and cardiovascular disease during prolonged cortisol exposure.

REPLACE is a multi-centre, double-blinded, placebo-controlled randomised controlled trial in patients with polymyalgia rheumatica or giant cell arteritis after cessation of prednisolone treatment. Criteria for randomisation are an AddiQoL-30 score ≤85 and/or plasma cortisol response to SST, 30-min p-cortisol >100 and 85; and (2) patients with a SST-stimulated cortisol ≤100 nmol/L.

The study is conducted in accordance with the Declaration of Helsinki, registered at the Clinical Trials Information System (CTIS: 2024-513822-53-00) and Clinicaltrials.gov (NCT05193396), and publications will be in accordance with the recommendations of the International Committee of Medical Journal Editors. The trial is monitored by local independent Good Clinical Practice units and overseen by the Danish Data Protection Agency (journal no. 21/27119), the Regional Committees on Health Research Ethics for Southern Denmark (project ID: S-20210076), the Danish Patient Safety Authority and the Danish Medicines Agency.

NCT05193396.

Suicide rates have increased over the last couple of decades globally, particularly in the United States and among populations with lower economic status who present at safety-net healthcare systems. Recently, predictive models for suicide risk have shown promise; however, a model for this specific population does not exist.

To develop a predictive risk model of suicide and intentional self-harm (ISH) for patients presenting at the psychiatric emergency department (ED) of JPS Health Network, a safety net medical and mental healthcare system in Texas.

The study used structured and unstructured electronic medical record (EMR) data (2015–2019) and local medical examiner data (2015–2020) to create predictors and outcome variables. All psychiatric ED notes during calendar years 2018 and 2019 were reviewed using natural language processing to identify presentations for any level of self-harm and subsequent manual review of identified visits to accurately classify ED presentations for treatment of an act of intentional self-harm meeting study criteria. Data from 15 987 patients were used to develop and validate a machine learning-based predictive model that leverages rolling window methodology to predict risk repeatedly across a patient’s trajectory. Feature engineering played a prominent role in defining new predictors.

The best model (XGBoost) achieved the area under the receiver operating characteristic curve of 0.81 for 30-day predictions and demonstrated concentration of ISH and suicide attempt events in high-risk quantiles of risk (65% had events in top 0.1% quantile). The predicted risk can be translated into a propensity of events (80% at the highest predicted risk) to facilitate clinical interpretation.

Machine learning-based models can be used with standard EMRs to identify patients presenting at the psychiatric ED with a high risk of ISH and suicide attempts within the next 30 days.

Integration of a predictive model can significantly aid clinical decision-making in safety-net psychiatric EDs.

Hypotension is a frequent complication after induction of general anaesthesia leading to end-organ injury, for which elderly and multimorbid patients are particularly susceptible. The extent of hypotension depends, among other factors, on the dose and rate of propofol administration. Target-controlled infusion systems are widely used to administer short-acting anaesthetics such as propofol and remifentanil. Commonly, induction is started with a fixed effect-site concentration. Titration, an alternative method of induction using an incremental augmentation of propofol, leads to a reduced induction dose and rate of propofol. We hypothesise that the titration method improves haemodynamic stability compared with conventional induction.

This multicentre, expertise-based randomised controlled trial takes place at four Swiss hospitals. Patients ≥55 years of age undergoing non-cardiac surgery under general anaesthesia using propofol target-controlled infusion are randomised to either a conventional or a titrated anaesthesia induction method. Patients, statisticians and, if resources allow, outcome assessors will be blinded. The primary endpoint is the mean arterial pressure under the individual baseline mean arterial pressure (area under threshold) during the first 30 min after start of induction. Secondary endpoints include the maximum deviation from baseline mean arterial pressure, haemodynamic rescue methods, propofol consumption and neurocognitive recovery after regaining consciousness.

A total of 320 patients are required to have an 80% chance of observing superiority of titration for the area under the threshold as significant at the 5% level, assuming a true difference of 100 mm Hg*min. The area under threshold and the maximum deviation will be compared between arms using mixed linear regression models.

Ethical approval has been obtained from all responsible ethics committees (BASEC2025-01007). The results will be presented at international meetings and published in peer-reviewed journals and may contribute to a change in clinical practice for anaesthesia induction using target-controlled infusion systems with propofol.

clinicaltrials.gov (NCT06980688) and www.humanforschung-schweiz.ch (HumRes67022).