Gram negative bloodstream infections (GN BSI) are a leading cause of mortality worldwide, and antibiotic treatment approaches remain understudied. BALANCE+ is a perpetual Bayesian adaptive platform trial to test multiple treatment questions for hospitalised patients with GN BSI. The vanguard phase objective was to test the feasibility of the main trial.

Adaptive platform trial with five initial domains of investigation, each with open label 1:1 randomisation.

Ten hospitals across four Canadian provinces.

Individuals admitted to hospital with blood cultures yielding Gram negative bacteria.

The five initial domains of investigation included: antibiotic de-escalation versus no de-escalation; oral transition to beta-lactam versus non-beta-lactam treatment; routine versus no routine follow-up blood cultures (FUBCs); central vascular catheter replacement versus retention; and, ceftriaxone versus carbapenem treatment for low risk AmpC organisms.

Domain-specific recruitment rates and protocol adherence.

During the vanguard phase, 719 patients were screened, of whom 563 (78.3%) were eligible, with 179 (31.8%) enrolled into the platform. The platform recruitment rate was 1.37 patients/site-week. Recruitment varied by domain: routine versus no FUBC domain 1.23 patients/site-week; oral beta-lactam versus non-beta-lactam domain 0.48; de-escalation versus no de-escalation domain 0.28; low risk AmpC domain 0.02; catheter replacement versus retention domain 0.01. Domain specific protocol adherence rates were 145/158 (91.8%) for routine versus no routine FUBC, 53/60 (88.3%) for oral beta-lactam versus non-beta-lactam, 26/33 (78.8%) for de-escalation versus no de-escalation, 3/3 (100%) for low risk AmpC, and 0/1 (0%) for line replacement versus retention. There was complete ascertainment of all study outcomes in hospital 170/170 (100%) and near complete ascertainment at 90 days 162/170 (95.3%).

The vanguard phase demonstrated overall trial feasibility by recruitment rate and protocol adherence, with differences across interventions, leading to a transition to the main BALANCE+ platform trial with minimal protocol modifications.

NCT05893147.

Inguinal hernia repair is one of the most frequently performed operations in the paediatric population and can be performed according to two approaches: open or laparoscopic. At present, decisive evidence about the best treatment strategy is lacking and consequently, there is an ongoing debate about the most (cost-)effective treatment for the paediatric inguinal hernia. The aim of the Hernia Endoscopic oR opeN repair In chIldren Analysis—trial (HERNIIA2-trial) is to estimate the (cost-)effectiveness of the laparoscopic percutaneous internal ring suturing (PIRS) technique compared with open repair in children aged 0–16 years with a primary unilateral inguinal hernia.

A national multicentre randomised controlled trial will be performed including 464 children aged 0–16 years with a primary unilateral inguinal hernia. Patients will be randomised between the open or PIRS technique. The primary outcome is the number of reoperations within 2 years after primary surgery. Secondary outcome measures are: operative and postoperative complications, total duration of surgery, postoperative pain, length of admission, time to normal daily activities, cosmetic appearance of the scar, social and healthcare costs and health-related quality of life. Furthermore, cost-effectiveness will be assessed from a societal and healthcare perspective.

The protocol was approved by the ethics committee of the Amsterdam University Medical Hospital. Informed consent will be obtained by parents and, if possible, according to age, by patient. The study will be conducted according to the principles of the Declaration of Helsinki (2013) and in accordance with the Medical Research Involving Human Subjects Act (WMO) and Good Clinical Practice. Study findings will be disseminated through scientific publications, conferences and patient-friendly materials. The national study network of participating centres will facilitate rapid dissemination and implementation within the Netherlands and potentially abroad.

ClinicalTrials.gov PRS (ID NCT06451432).

Process evaluation provides insight into how interventions are delivered across varying contexts and why interventions work in some contexts and not in others. This manuscript outlines the protocol for a process evaluation embedded in a hybrid type 1 effectiveness-implementation randomised clinical trial of incremental-start haemodialysis (HD) versus conventional HD delivered to patients starting chronic dialysis (the TwoPlus Study). The trial will simultaneously assess the effectiveness of incremental-start HD in real-world settings and the implementation strategies needed to successfully integrate this intervention into routine practice. This manuscript describes the rationale and methods used to capture how incremental-start HD is implemented across settings and the factors influencing its implementation success or failure within this trial.

We will use the Consolidated Framework for Implementation Research (CFIR) and the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) frameworks to inform process evaluation. Mixed methods include surveys conducted with treating providers (physicians) and dialysis personnel (nurses and dialysis administrators); semi-structured interviews with patient participants, caregivers of patient participants, treating providers (physicians and advanced practice practitioners), dialysis personnel (nurses, dieticians and social workers); and focus group meetings with study investigators and stakeholder partners. Data will be collected on the following implementation determinants: (a) organisational readiness to change, intervention acceptability and appropriateness; (b) inner setting characteristics underlying barriers and facilitators to the adoption of HD intervention at the enrollment centres; (c) external factors that mediate implementation; (d) adoption; (e) reach; (f) fidelity, to assess adherence to serial timed urine collection and HD treatment schedule; and (g) sustainability, to assess barriers and facilitators to maintaining intervention. Qualitative and quantitative data will be analysed iteratively and triangulated following a convergent parallel and pragmatic approach. Mixed methods analysis will use qualitative data to lend insight to quantitative findings. Process evaluation is important to understand factors influencing trial outcomes and identify potential contextual barriers and facilitators for the potential implementation of incremental-start HD into usual workflows in varied outpatient dialysis clinics and clinical practices. The process evaluation will help interpret and contextualise the trial clinical outcomes’ findings.

The study protocol was approved by the Wake Forest University School of Medicine Institutional Review Board (IRB). Findings from this study will be disseminated through peer-reviewed journals and scientific conferences.

NCT05828823.

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.

Glucosamine is a commonly used ‘over the counter’ dietary supplement. Previous research has identified an association between glucosamine use and several positive health outcomes. However, a plausible biological mechanism for these associations has not yet been identified, meaning the causality of these relationships remains unclear. A protective effect of glucosamine on the vascular endothelium has been suggested as one such possible mechanism. Albuminuria is an early marker of endothelial dysfunction within the kidney and is associated with progression of kidney disease and adverse cardiovascular outcomes. In order to provide insights into the potential biological mechanisms underlying a protective association of glucosamine use with health outcomes, we evaluated evidence for an association between glucosamine use and albuminuria in UK Biobank (N=436 200).

Univariable and multivariable ordinal logistic regression were performed to evaluate evidence for an association between self-reported glucosamine use and albuminuria (measured as urine albumin creatinine ratio (uACR) categories). As a secondary analysis, we performed Mendelian randomisation (MR) to demonstrate the difficulties in inferring causality in this relationship using currently available data, using summary genetic data from UK Biobank and CDKGen (N=67 452).

We found that people who used glucosamine were more likely to be in a lower uACR group (OR 0.81, 95% CI 0.80 to 0.83, px10^–16). This association was robust to sensitivity analyses and was maintained after adjustment for age, sex and measures of obesity. In our MR analysis, we found little evidence for an association of genetically proxied glucosamine use on albuminuria (change in log uACR (mg/g) per SD change in genetic liability=1.11, 95% CI –3.01 to 5.23, p=0.60).

We found that detectable albuminuria was common in UK Biobank participants and we are the first to show that use of glucosamine supplements was associated with lower levels. Though this fits with a plausible biological role of the vascular endothelium in a potential protective effect of glucosamine use on many health outcomes, whether this relationship is causal or confounded remains unclear. We further discuss the inherent difficulties in using genetic instruments to proxy supplement use in MR analyses and highlight the need for a genome-wide association study of measured circulating glucosamine levels.

While loneliness has been recognised as a global public health concern, there are still knowledge gaps about how to prevent or reduce loneliness. The Social Relationship Expectations (SRE) Framework (Akhter-Khan et al, 2023) has been developed to enhance mechanism-based interventions targeting individuals’ expectations for social relationships. However, no scale has yet been developed to measure these expectations. We aim to measure SRE across the six interdependent dimensions identified in the theoretical framework, across diverse settings. This protocol outlines the methodology for developing the SRE scale.

The scale will be developed using both inductive and deductive techniques in a multicountry observational study. First, items will be extracted from published qualitative studies on loneliness and SRE across 15 lower-middle-income countries and from a qualitative focus group study with older Myanmar and Thai adults. Second, using a Delphi process for item development, experts across five world regions (Africa, the Americas, Asia, Europe and Oceania) will be involved in the item selection and scale creation process. A preliminary item pool will be administered in English, German and Chinese. Classical test theory as well as network analysis will be used to assess the dimensionality of the scale, understand item relationships and clusters, and select the final items for the SRE scale.

Ethics approval for the scale development has been obtained from King’s College London (reference number: MRSP-24/25-46512). Informed consent will be obtained from all participants prior to completing the cognitive interviews and online surveys. Results will be disseminated in peer-reviewed journals in collaboration with coauthors across different countries and disciplines.

The Maharashtra Anaemia Study 3 (MAS 3) aims to (1) Investigate the nutritional, environmental, and economic impacts on haemoglobin concentration/anaemia, (2) Identify the underlying micronutrient causes of anaemia and (3) Investigate the association between anaemia and physical and cognitive development of Indian children during their first 18 years of life. This paper introduces the MAS 3 cohort, which consists of data collected from the participants in the prospective Pune Maternal Nutrition Study from the antenatal period to children at 18 years of age (1996–2014) in the Maharashtra state, India.

Recruitment of 2466 married non-pregnant women, and their husbands, took place between June 1994 and April 1996 in six villages, approximately 50 km from Pune city in India. Women were followed up monthly to identify those who became pregnant. A total of 797 pregnant women were followed up for data collection at or near gestational week 18 and 28, with further data collection for women and children occurring within 72 hours of delivery, for both live and stillbirths. Of the 797 women, 710 were included in the MAS 3 cohort, and long-term follow-up of children occurred at 6 years, 12 years and 18 years of age.

In the MAS 3 cohort, most mothers (73%) were aged between 18 and 25 years at the time of their final prepregnancy visit (baseline), and half (55%) belonged to families of middle-upper socioeconomic status (SES). At the children’s baseline (birth) visit, children had a mean birth weight of 2630 g (SD: 376), with one third (31%) of low birth weight. At the 6-year, 12-year and 18-year follow-up visits, data were available for 706 (99%), 689 (97%) and 694 (98%) children.

MAS 3 will be used to address a number of research objectives, including (1) Trends of haemoglobin and anaemia-related micronutrients from age 6 to 18 years, (2) Micronutrient causes of anaemia during childhood, (3) Prevalence and risk factors for maternal anaemia and childhood anaemia, (4) Impact of maternal anaemia on immediate birth outcomes and (5) Intergenerational risk factors associated with anaemia.

Cirrhosis is a major cause of morbidity and mortality. Patients with decompensated cirrhosis, or end-stage liver disease (ESLD), have a high symptom burden and an increased mortality risk. Yet, the uptake of palliative care in patients with ESLD remains low and variable. Despite robust evidence of the value of home palliative care in other advanced diseases, this has not been well studied in patients with ESLD. Hence, the primary aim of this study is to explore the implementation, feasibility and acceptability of home palliative care in patients with ESLD and healthcare professionals. We also aim to describe its impact on the quality of life (QoL), mood, symptom burden, caregiver burden and healthcare utilisation of patients with ESLD.

The study is a single-centre, mixed-methods feasibility study. Eligible patients include those with decompensated liver cirrhosis who are admitted under the gastroenterology and hepatology service and fulfil the Supportive and Palliative Care Indicator Tools (SPICT) criteria. Recruited patients will be followed up by a multi-disciplinary homecare team led by a palliative care physician for 6 months. Both qualitative and quantitative measures will be used to evaluate the primary aim and include the uptake of the service by both eligible patients and physicians. Semistructured interviews with key stakeholder groups will be conducted to determine their perspectives and experiences. Secondary outcome measures include changes in health-related QoL using the Chronic Liver Disease Questionnaire, depression severity, goals of care discussions, patient symptom burden, caregiver burden and healthcare utilisation.

This study will adhere to the Declaration of Helsinki and has been approved by the research ethics committee of the National Healthcare Group (DSRB (Domain Specific Review Board) reference: 2023/00852). Results will be submitted for publication in international peer-reviewed journals.

Sex selection is not permitted in Australia; however, there are indirect means for such selection to occur, for example, through sex identification and the early termination of pregnancy. Indirect evidence for such selection, if any, may be inferred from variations in the ‘sex ratio at birth’ (SRB) among different populations. This study aims to characterise the SRBs over 11 years in spontaneous and assisted births in the largely migrant population of Western Sydney.

This is a retrospective cohort study.

Western Sydney Local Health District over three maternity hospitals.

A total of 109 931 births between 2011 and 2020, where gender was assigned at birth, were included in the study.

The primary outcome measured was the SRB between ethnicities and mode of conception.

There was a higher male to female SRB for mothers born in China (SRB=1.12) compared with mothers born in Australia (SRB=1.05). Mothers from China were 1.1 times more likely to have a son. Otherwise, there was no significant difference with the SRB according to year, parity and mode of conception.

Among the Western Sydney population, mothers born in China show a higher male SRB, reflecting a possible sex preference. However, this study is not without some limitations, for which purpose further study is warranted.

Total diet replacements (TDRs) and weight loss medications (WLMs) have proven effective in producing substantial weight loss for individuals with obesity. Evidence is lacking on whether combining these treatments is effective and cost-effective in primary care for adults with obesity class I (body mass index (BMI) 30–34.9) or uncomplicated obesity class II or higher (BMI≥35 without obesity-related disease).

LightCARE is a 2-year 1:1 randomised, parallel-group, clinical superiority trial with blinded outcome assessment evaluating the benefits and harms of an intensive weight loss (IWL) intervention compared with usual care for adults with obesity in Denmark and the UK. The trial will include 400 participants aged 18–60 years with obesity class I or uncomplicated obesity class II or higher. The IWL programme aims to achieve and maintain a weight loss of ≥20% through a flexible and individualised combination of TDR, behavioural support, including physical activity and sleep guidance, and WLM if needed and will continue for 2 years. The control group will receive usual care offered in each country, typically consisting of brief behavioural support for weight loss. The primary outcome is body weight 2 years after randomisation. Secondary outcomes will include the proportion of participants achieving ≥20% weight loss, Short-Form-36 Mental Component Score, 4-m gait speed and Metabolic Syndrome Severity-Z score. Serious adverse events, the incidence of eating disorders and bone mineral density will be evaluated as safety outcomes. We will also examine the cost-effectiveness of the intervention, within the trial and in the longer term through modelling. We will conduct a process evaluation to inform any future implementation.

Ethical approval was granted in Denmark (December 2023, H-23051332) and the UK (August 2024, 24/SC/0210). Findings from the trial will be disseminated through peer-reviewed journals and scientific conferences.

NCT06321432.

Ovarian cancer remains a significant clinical challenge due to its aggressive nature and high mortality rate. Tumour-infiltrating lymphocytes (TILs) play a critical role in the tumour microenvironment, influencing treatment response and patient survival across various cancer types, including ovarian cancer. A systematic review is warranted to consolidate evidence on TILs as prognostic biomarkers in ovarian cancer, with the goals of integrating them into clinical practice to enhance patient outcomes. This study aims to assess the prognostic significance of TILs in ovarian cancer.

A comprehensive literature search will be conducted across multiple databases, including PubMed, Embase, Web of Science, Scopus, Cochrane Library, CINAHL, ScienceDirect and LILACS. No restrictions regarding publication date or language will be applied. Original studies evaluating the role of TILs in women with ovarian cancer will be considered for inclusion. Two independent authors will screen titles and abstracts, and any discrepancies will be resolved through discussion with a third author. The risk of bias in included studies will be assessed using the Quality in Prognosis Studies (QUIPS) tool. Data synthesis will be performed using R software (V.4.3.1).

This study reviews the published data; thus, obtaining ethical approval is unnecessary. The findings of this systematic review will be published in a peer-reviewed journal.

CRD42024543955.

In addition to hypertension, the constellation of metabolic abnormalities (diabetes mellitus, dyslipidaemia and/or obesity) independently increases the incidence and severity of cardiovascular diseases, and this is compounded by the modern lifestyle and ageing society. The prevalence of metabolic syndrome is high and non-hypertensive heart failure is common in Asians. Adverse cardiac remodelling is an important substrate for cardiac dysfunction in the onset and progression of heart failure and its amelioration improves outcomes and prognosis. A better understanding of metabolic-driven cardiac remodelling is warranted due to the rising prevalence and complexity of metabolic syndrome and strong interests in targeted therapy.

Response of the myocardium to hypertrophic conditions in the adult population is a prospective observational cohort study with an aim to establish the significance of cardiac remodelling by cardiovascular magnetic resonance (CMR). The current recruitment target is 2000 participants. Expanding from the initial population with hypertension, the study examines adults with cardiometabolic conditions, including diabetes, dyslipidaemia, obesity and fatty liver disease. Eligible patients are identified at National Heart Centre Singapore, primary care clinics and through public outreach. Physical, clinical, imaging and biochemical data are collected. Cardiac remodelling features pertaining to hypertrophy, fibrosis and functional changes are assessed on CMR. Body adiposity is mapped by MRI across the heart, liver and abdomen. Outcome data are adjudicated and follow-up assessment will be available in a subset of participants. Blood biomarkers will be investigated in relation to imaging findings. Cross-sectional analysis will establish the implication of cardiometabolic disease towards cardiac remodelling, while follow-up and outcome analysis will infer on disease progression and prognosis.

The study was approved by the SingHealth Centralised Institutional Review Board (2015/2603). Written informed consent is obtained from all participants. Study findings will be reported in peer-reviewed journals and at scientific conferences.

ClinicalTrials.gov, NCT02670031.

The aims of this study were (1) To investigate the availability of NHS funded in vitro fertilisation (IVF) treatment for individuals affected by Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) from all Integrated Care Boards (ICBs) across England and (2) To assess the ethical implications of piecemeal funding for those with MRKH.

This was a mixed-methods study containing both quantitative and qualitative data. We filed freedom of information (FOI) act requests on 01/06/2023 for all 42 ICBs across England via secure email.

The study focused on England.

All 42 ICBs across England were contacted.

The FOI requests asked for information concerning the provision of funded IVF for uterine factor infertility, and if this included individuals with MRKH. Where assistance was available, we recorded what it comprised along the IVF cycle. If IVF was not offered, we recorded the rationale provided by the ICB.

Responses were received from all 42 ICBs across England. Seven stated that they would fund IVF and cryopreservation of embryos to women with MRKH and other absolute uterine factor infertility diagnoses (NHS Humber and North Yorkshire, NHS Dorset, NHS Devon, NHS Cornwall and Isles of Scilly, NHS Buckinghamshire, Oxford and Berkshire, NHS South Yorkshire and NHS West Yorkshire). However, the number of cycles, the length of cryopreservation and whether they would fund embryo transfer into a surrogate differed between ICBs.

Of the remainder, three (NHS Leicester, Leicestershire and Rutland, NHS Greater Manchester and NHS Hampshire and Isle of Wight) described some provision of fertility preservation (cryopreservation of oocytes or embryos) for women with uterine factor infertility, two of whom suggested their policy may include women with MRKH (NHS Greater Manchester and NHS Hampshire and Isle of Wight). Two ICBs (NHS Gloucester and NHS Bedford, Luton and Milton Keynes) explained that individual funding applications would be considered when made by clinicians on the patient’s behalf, but no information was provided on how many times requests had been made and granted. The remaining 30 ICBs explained that no part of a surrogacy pregnancy would be funded, owing to concerns around commercial surrogacy, which is illegal in the UK.

This work has revealed that only a small proportion of ICBs (7/42, 17%) treat women with MRKH like any other woman applying for NHS fertility treatment. The study revealed that decisions by ICBs not to fund IVF treatments based on concerns about commercial surrogacy create significant inequities. It unfairly penalises individuals with MRKH who require surrogacy as part of their fertility treatment. These individuals face a unique set of reproductive challenges, and denying them access to NHS-funded IVF treatments exacerbates existing inequalities. Furthermore, if individuals with MRKH accept that the expenses of the surrogate will be met by them rather than the ICB, it is unjustifiable to deny them the IVF component of the treatment if they meet all the other criteria for eligibility. Moreover, the fact that some ICBs do fund IVF for individuals with MRKH indicates that legal concerns regarding surrogacy are unfounded and inconsistently applied. This discrepancy highlights the need for a standardised approach that ensures equitable access to fertility treatments across all regions.

Stroke is a leading cause of disability and mortality worldwide, with upper limb dysfunction being among its most common effects. Compression therapy has recently gained growing interest as an adjunct to other rehabilitation interventions for managing upper limb dysfunction among stroke survivors. However, the evidence for its effectiveness remains inconsistent and equivocal. Therefore, this systematic review aims to assess the effectiveness of compression therapy in managing upper limb dysfunction in patients with stroke.

A systematic search of databases (PubMed, Scopus, Web of Science, CINAHL, Cochrane Library, Embase, PEDro, OTseeker, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform) will be conducted to identify peer-reviewed studies and relevant grey literature on compression therapy on upper limb dysfunction after stroke. Two reviewers will independently screen, select and extract data, with discrepancies resolved through discussion or involvement of a third reviewer. Outcomes of interest include clinical measures of upper limb function, activity, participation and safety (ie, adverse effects). Risk of bias will be assessed using the Cochrane RoB 2 for randomised studies, the Risk Of Bias In Non-randomised Studies of Interventions for non-randomised studies. The certainty of evidence across types of compression therapy and outcomes will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation approach. Data will be narratively synthesised, and a meta-analysis will be performed if feasible. The review will be reported following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and will be conducted from September 2025 to December 2025.

This systematic review does not require ethical approval as only secondary data will be used. This review will synthesise the body of evidence on the effectiveness of compression therapy in managing poststroke upper limb dysfunction. Results will then be disseminated through a peer-reviewed publication to inform research and clinical practice.

CRD42024625815.

Patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) are considered to have a symptomatic venous thromboembolism (VTE) risk of 1.0%–1.5% despite thromboprophylaxis. Fast-track treatment protocols have substantially lowered the VTE risk in most patients. Hence, the majority of patients may be unnecessarily exposed to the burden and risk of thromboprophylaxis. On the contrary, there are still patients with a high VTE risk who develop VTE despite thromboprophylaxis. Thus, tailored thromboprophylaxis treatment may potentially reduce both VTE and bleeding risk.

The DISTINCT (inDividual, targeted thrombosIS prophylaxis versus the standard ‘one-size-fits-all’ approach in patients undergoing Total hIp or total kNee replaCemenT) trial is a national, multicentre, randomised, multiarm, open-label trial. The main objective is to study whether tailored thromboprophylaxis reduces the occurrence of symptomatic VTE (primary outcome) and major bleeding (primary safety outcome) within 90 days after THA/TKA in comparison with standard thromboprophylaxis. Patients with a low, intermediate or high predicted VTE risk (based on the Thrombosis Risk Prediction following total hip and knee arthroplasty score (TRiP(plasty) score)) will be included in the DISTINCT-1, DISTINCT-2 or DISTINCT-3 studies, respectively. In the DISTINCT-1 trial, 3478 patients will be randomly allocated to receive either in-hospital thromboprophylaxis or standard prophylaxis. In the DISTINCT-2 cohort study, 2500 patients will receive standard prophylaxis. In the DISTINCT-3 trial, 4100 patients will be randomly allocated to receive either 6 weeks of high-dose thromboprophylaxis or standard prophylaxis. Standard prophylaxis consists of a low dose of any approved thromboprophylactic agent for 4 weeks. We hypothesise that (1) the efficacy of in-hospital only thromboprophylaxis is non-inferior in preventing VTE and equally safe compared with standard prophylaxis in patients with a low VTE risk (DISTINCT-1) and (2) prolonged high-dose thromboprophylaxis is superior in preventing VTE as compared with standard prophylaxis in patients with a high VTE risk (DISTINCT-3). Patients with intermediate VTE risk will be observed to evaluate VTE and bleeding rates (DISTINCT-2).

The protocol has been approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft, EU-trial-number 2023-510186-98. Study results will be disseminated through peer-reviewed journals and during international conferences.

NCT06581965.

Head and neck cancer (HNC) affects the mouth, throat, salivary glands, voice box, nose or sinuses. Every year, over 12 000 people in the UK are diagnosed with HNC. Neck dissection is a key, surgical component of patient care. However, many people experience postoperative restriction in shoulder and neck movements, pain, fatigue and low mood, with only half ever returning to work.

Getting Recovery Right After Neck Dissection (GRRAND) is a two-arm, multicentre, pragmatic randomised controlled trial. The trial aims to compare clinical and cost-effectiveness of a personalised physiotherapy programme (GRRAND programme) versus usual practice, National Health Service (NHS), postdischarge care.

The planned sample size is 390 participants. Participants will be recruited from across UK sites and followed up for 12 months. The primary outcome is the shoulder pain and disability index at 12 months. Economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data, including pain, function, health-related quality of life, mental well-being, health resource use and adverse events, will be collected at 6 weeks, 3, 6 and 12 months, with exercise adherence at 6 weeks. A process evaluation will determine how GRRAND is implemented, delivered and received across clinical settings, exploring what works, for whom and under what conditions. Analysis will be on an intention-to-treat basis and reported inline with the Consolidated Standards of Reporting Trials statement.

The trial was approved by the London-Brent Research Ethics Committee (ref: 24/LO/0722) on 15 October 2024. Trial results will be disseminated via peer-reviewed publications, presentations at national and international conferences, in lay summaries and social media. This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials checklist.

ISRCTN13855775.

Little research has been done on post-COVID symptoms at 24 months postinfection and on the association these may have on health-related quality of life (HRQOL).

We assessed the prevalence and severity of post-COVID symptoms and quantified EuroQol 5 Dimension 5 Level (EQ-5D-5L), self-perceived health question (EuroQol Visual Analogue Scale (EQ-VAS)) and health utility scores (HUS) up to 24 months follow-up.

The longitudinal multiple cohort CORona Follow-Up (CORFU) study combines seven COVID-19 patient cohorts and a survey among the general public. The participants received questionnaires on several time points. Participants were stratified by: without a known SARS-CoV-2 infection (control group), proven SARS-CoV-2 infection but non-hospitalised, proven SARS-CoV-2 infection hospitalised to the ward, and proven SARS-CoV-2 infection hospitalised to the intensive care unit (ICU).

In this study, data of seven COVID-19 patient cohorts and a survey among the general public are included.

Former COVID-19 patients and controls participated in this cohort study.

Former COVID-19 patients and non-COVID-19 controls were sent questionnaires on symptoms associated with post-COVID condition. The CORFU questionnaire included 14 symptom questions on post-COVID condition using a five-level Likert-scale format. Furthermore, HRQOL was quantified using the EuroQol EQ-5D-5L questionnaire: EQ-VAS and the EQ-5D-5L utility score. The EQ-5D-5L questionnaire includes five domains that are scored on a five-point Likert scale: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

A total of 901 participants (and 434 controls) responded at 24 months follow-up. In all former COVID-19 patients, the presence of post-COVID condition at 24 months was observed in 62 (42.5%, 95% CI 34.3% to 50.9%) of the non-hospitalised patients, 333 (65.0%, 95% CI 60.7% to 69.2%) of the hospitalised ward patients and 156 (63.2%, 95% CI 56.8% to 69.2%) of the ICU patients, respectively (p

Many former COVID-19 patients experience post-COVID symptoms at 24 months follow-up, with the highest prevalence in hospitalised participants. Also, former patients reported a lower HRQOL.

The CORFU study was registered at clinicaltrials.gov (registration number NCT05240742).

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

Cross-sectional non-inferiority validation study.

Tertiary academic hospital.

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

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

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

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

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

Sepsis is a major cause of death both globally and in the United States. Early identification and treatment of sepsis are crucial for improving patient outcomes. International guidelines recommend hospital sepsis screening programmes, which are commonly implemented in the electronic health record (EHR) as an interruptive sepsis screening alert based on systemic inflammatory response syndrome (SIRS) criteria. Despite widespread use, it is unknown whether these sepsis screening and alert tools improve the delivery of high-quality sepsis care.

The Sepsis Electronic Prompting for Timely Intervention and Care (SEPTIC) master protocol will study two distinct populations in separate trials: emergency department (ED) patients (SEPTIC-ED) and inpatients (SEPTIC-IP). The SEPTIC trials are pragmatic, multicentre, blinded, randomised controlled trials, with equal allocation to compare four SIRS-based sepsis screening alert groups: no alerts (control), nurse alerts only, prescribing clinician alerts only, or nurse and prescribing clinician alerts. Randomisation will be at the patient level. SEPTIC will be performed at eight acute-care hospitals in the greater New York City area and enrol patients at least 18 years old. The primary outcome is the percentage of patients with completion of a modified Surviving Sepsis Campaign (SSC) hour-1 bundle within 3 hours of the first SIRS alert. Secondary outcomes include time from first alert to completion of a modified SSC hour-1 bundle, time from first alert to individual bundle component order and completion, intensive care unit (ICU) transfer, hospital discharge disposition, inpatient mortality at 90 days, positive blood cultures (bacteraemia), adverse antibiotic events, sepsis diagnoses and septic shock diagnoses.

Ethics approval was obtained from the Columbia University Institutional Review Board (IRB) serving as a single IRB. Results will be disseminated in peer-reviewed journal(s), scientific meeting(s) and via social media.

ClinicalTrials.gov: NCT06117605 and NCT06117618.