Ear, nose and throat (ENT) conditions are highly prevalent in primary and secondary care, yet patients frequently face prolonged waits for specialist review. In England, over half of ENT patients wait beyond the NHS 18-week referral-to-treatment target. Many of these cases can be effectively managed with advice and non-surgical interventions, presenting an opportunity for remote service innovation.

This study aims to evaluate the clinical effectiveness, cost-effectiveness, acceptability and environmental sustainability of a digitally enabled remote ENT clinic model compared with traditional face-to-face pathways.

This single-centre, mixed-methods, prospective cohort study will be conducted at University Hospitals Birmingham NHS Foundation Trust. Remote clinics will use trained staff to collect diagnostic data (including endoscopic imaging and boothless hearing tests) for consultant review via secure cloud-based software. Quantitative analysis will assess patient outcomes, costs, waiting times, carbon footprint and satisfaction. Qualitative data from semi-structured interviews with patients, clinicians and managers will explore acceptability, scalability and barriers to implementation. The qualitative data will be analysed using the framework methodology, according to the non-adoption, abandonment, scale-up, spread and sustainability framework, while the strengthening the reporting of observational studies in epidemiology framework will be used to guide the reporting of quantitative data. Cost-effectiveness analyses will follow NICE guidelines, while environmental impact will be measurement will be informed by the sustainability in quality improvement framework. Recruitment will be aiming for 300 completed datasets and 30–35 interviews.

Ethical approval has been granted (IRAS 350908; REC 25/SW/0116). Findings will be disseminated via conferences, peer-reviewed journals and institutional communication channels.

Primary biliary cholangitis (PBC) is a rare chronic cholestatic disease that despite current therapy has significant ongoing unmet needs, including risks of cirrhosis and life-impairing symptoms. The current treatment approach is a step-up model, wherein first-line therapy, ursodeoxycholic acid (UDCA), is given for a minimum of 12 months before the addition of second-line therapy is considered for non-responding patients. This ‘waiting to fail’ approach, focused on the needs of low-risk patients, allows, we postulate, a key process of biliary epithelial cell (BEC) senescence to become established, driving accelerated bile duct loss and aggressive disease. Preclinical mouse modelling has shown that early use of the farnesoid X receptor agonist obeticholic acid (OCA), currently only used as second-line therapy following UDCA failure, reverses BEC senescence, changing the clinical course of disease. Here, we describe the design of the Optimising Primary thErapy in pRimAry biliary cholangitis (OPERA) trial. The aim of OPERA is to explore a new paradigm for disease-modifying treatment of PBC: risk-informed early treatment stratification, with patients at increased risk offered UDCA and OCA combination with the goal of complete biochemical remission.

OPERA is a multicentre, randomised, double-blind, placebo-controlled trial of OCA in combination with UDCA, as first-line treatment for high-risk PBC. This is a multicentre trial in England, which will be undertaken in specialist clinics in secondary/tertiary referral centres (or as per local set up). These centres will be specialists in the area of PBC management and will manage patients from across their local region. OPERA will recruit and randomise 106 adults, within 6 months of PBC diagnosis, who are at an enhanced risk of non-response to standard first-line therapy, between either: (1) UDCA and OCA or (2) UDCA and matched placebo in a 1:1 ratio. The primary efficacy outcome measure is the percentage of participants showing normalisation of serum alkaline phosphatase and total bilirubin values at 26 weeks (disease remission).

Favourable ethical opinion was received from London – Riverside Research Ethics Committee (reference: 22/LO/0878). Potential participants will be fully informed of their rights and the benefits and harms of the trial by the research team before giving informed consent to participate in the trial. Results will be disseminated in peer-reviewed publications, at national and international conferences, in peer-reviewed journals and to participants and the public (using lay language).

ISRCTN17176388.

To assess the acceptability and adoption of multiparameter point-of-care testing (POCT) devices for the diagnosis and management of non-communicable diseases (NCDs) at the primary healthcare level in a resource-limited region of Peru.

Qualitative case-control process evaluation.

Eight primary healthcare facilities in northern Peru, including both urban and rural centres, where routine chronic care and laboratory services are provided.

Sixty-three participants: 36 patients, 12 laboratory technicians, 10 healthcare professionals and five facility heads. Eligible patients were ≥18 years, residing in the catchment area, with or without prior NCD diagnoses. Healthcare workers, including physicians, nurses, laboratory staff and facility managers.

Multiparameter POCT devices were installed in four intervention facilities, accompanied by staff training and community awareness activities, while four control facilities continued with conventional laboratory diagnostics.

Primary outcome: perceptions of patients and healthcare workers regarding the acceptability and adoption of POCT devices. Secondary outcomes: identification of facilitators and barriers to implementation, including infrastructure, supply chains and training gaps.

(1) Individuals: POCT was valued for speed and comfort, but concerns over accuracy were mentioned. (2) Intervention characteristics: laboratory staff valued POCT’s practicality in emergencies, but noted limitations in handling multiple samples. (3) Outer setting: urban centres outperformed rural facilities, with more staff and longer operating hours. (4) Inner setting: calibration gaps impacted POCT and conventional test reliability, requiring quality control and training. (5) Process: clear staff communication boosted patient confidence in POCT, but inconsistent training could lead to reliability doubts.

Multiparameter POCT devices show promise for enhancing NCD care in resource-limited primary healthcare settings, particularly in rural areas. However, their sustainability depends on broader health system reforms, including reliable supply chains, expanded training and stronger quality assurance mechanisms. Further research should examine strategies for embedding POCT within national regulatory and policy frameworks.

Diagnostic errors in primary care are common, particularly in the interpretation and follow-up of abnormal haemoglobin (Hgb) and estimated glomerular filtration rate (eGFR) results. These errors frequently result in missed or delayed diagnoses of serious conditions such as anaemia and chronic kidney disease. This protocol describes a stepped-wedge cluster randomised controlled trial designed to evaluate a novel, evidence-based, team-based intervention aimed at improving diagnostic safety and efficiency.

The study will be conducted across 12 University of Texas Physicians (UTPs) primary care clinics in Houston, Texas, USA. Adult patients (≥18 years) with newly identified abnormal Hgb or eGFR results will be eligible for inclusion. The intervention integrates automated tracking of abnormal laboratory results, nurse navigators to support patient follow-up and engagement, and clinical pathologists to provide diagnostic guidance to primary care providers. The primary outcome is diagnostic safety, defined as the proportion of patients who receive a correct diagnosis within 6 months. Secondary outcomes include diagnostic efficiency, appropriate test utilisation, cost-effectiveness, patient activation and implementation metrics such as acceptability, fidelity and sustainability. The study will also explore barriers and facilitators to successful implementation using mixed-methods evaluation.

This trial has been approved by the Institutional Review Board at The University of Texas Health Science Center at Houston. Study results will be disseminated through peer-reviewed publications and conference presentations, and findings will be reported to UTP leadership to inform potential system-wide implementation.

NCT05735314.

The optimal strategy for induction of labour (IOL) in cases of prelabour rupture of membranes (PROM) with an unfavourable cervix is elusive. No study conducted in nulliparous women has shown any one induction method to be superior to any other. In this project, we seek to determine whether IOL with balloon catheter and oxytocin can (1) increase rate of delivery

We are conducting a multicentre, randomised, controlled, open-label therapeutic trial with two parallel arms on nulliparous women with unfavourable cervix showing PROM at term without spontaneous labour.

After 12 hours of PROM, women are randomly assigned to one of two study groups. One group is treated with a balloon catheter for 12 hours, with oxytocin administered after 6 hours. If the balloon is expelled earlier than 6 hours after insertion and the cervix is still unfavourable, another balloon is placed. The other group (control) is treated with 25 µg oral PGE1 every 2 hours until labour starts. After a maximum of eight administrations and a timelapse of 4 hours, if there are no effective uterine contractions, the induction is continued with oxytocin infusion and epidural analgesia if the patient requests it. A total of 520 women will be recruited in five university hospitals in France and randomised at a 1:1 ratio with stratification by study centre.

Main inclusion criteria are nulliparous women with gestational age ≥37 weeks, PROM without labour beyond 12 hours, unfavourable cervix (Bishop score

The hierarchical primary endpoints are: (1) Proportion of patients vaginally delivered

The RUBAPRO2 trial was approved by the French national agency for drug safety and committee for protection of persons involved in biomedical research on 15 September 2022. Informed written consent will be obtained from all participants.

NCT05568745.

Music-based training programmes, such as learning how to play an instrument or sing in a choir, have been suggested as potential interventions for promoting healthy brain ageing in older adults at risk of cognitive decline because of their ability to enhance cognitive functions and potentially promote neuroplasticity. However, there is limited empirical evidence in older adults at risk of dementia, especially that evaluates both piano and singing interventions and their effects on cognition and neuroplasticity. In this protocol, we outline a study to assess the efficacy of keyboard and singing music training programmes on reducing cognitive decline and other outcomes in older adults with Mild Cognitive Impairment (MCI).

This randomised, single-blind, controlled, parallel-group trial aims to enrol 432 individuals with MCI from the community in Sydney, Australia. Participants are randomly allocated to participate in either keyboard lessons, singing lessons or a film discussion control group once a week for 3 months. The primary objective is to assess the effectiveness of two music training programmes (keyboard and choral singing) for enhancing verbal memory after 3 months compared with control. Additionally, we will examine how these music-based interventions affect other aspects of cognition, mood, sleep, overall well-being, markers of brain plasticity and blood biomarkers of Alzheimer’s disease and neurodegeneration. Tertiary objectives are to identify factors that impact the success of the interventions, such as participation rates, engagement levels and key demographic and clinical features. Outcomes are collected at baseline and at 3 and 9 months. The primary endpoint analysis will include all randomised participants to estimate the treatment effect using intention-to-treat principles. Primary and secondary outcomes will be analysed using linear mixed models and effect size measures will be calculated.

This study will be the first robust, randomised controlled trial to assess the potential and relative value of music engagement for cognitive decline in high-risk MCI individuals, as well as broader effects on other markers of mental health, well-being and neurodegeneration. Co-designed with implementation in mind, the music interventions can potentially be delivered within memory clinic or community settings.

The Sydney University Human Research Ethics Committee (2023-026) has approved this protocol. The trial findings will be shared through conferences, publications and media.

Australian and New Zealand Clinical Trials Registry (ACTRN12623000407695), Registered 21/04/2023 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385552

2.02 29/11/2024.

This project explores the feasibility of setting up a neuropsychiatric de-identified database (DiD) and a Research Register (RR) to collect, analyse, monitor and systematically report clinical data for people with intellectual disabilities (PwIDs) and epilepsy.

A multicentre project designed to collect de-identified data from clinical records at three adult ID specialist services in England and Wales and to develop an RR of PwID and epilepsy. Patients added to the DiD will be identified from patient clinic lists, clinic letters, in-house databases and electronic systems. Patients to be added to the RR will also be identified through attendance for regular review at clinic appointments. The collected data will be entered into the Research Electronic Data Capture (REDCap) database. Personal details of PwID and their consultees will also be collected from participants who consent to be on the RR. Around 600 PwID and epilepsy (200 per site) will be added to the DiD at the three sites, while around 45–60 participants (15–20 per site) are anticipated to be added to the RR. Data analysis will involve using descriptive statistics to summarise feasibility outcomes, such as screening and recruitment rates, as well as the completeness of the collected data. The characteristics of the participants (demographic, ID classification, clinical, epilepsy history and antiseizure medication) will be summarised descriptively. Progression will be assessed using the Red/Amber/Green stop-go criteria to determine if a national register should be created.

Ethical approval (24/NW/0210) has been obtained from the Northwest-Haydock Research Ethics Committee and the University of Plymouth Faculty Research Ethics and Integrity Committee (reference no. 5284). The project is funded by Jazz Pharmaceuticals as an independent investigator-initiated support grant and, as such, has received independent peer review.

NCT06780501.

Leishmaniases are a group of vector-borne diseases caused by parasites of the genus Leishmania, which are renowned for increasing global spread due to factors like climate change, globalisation, urbanisation and migration. Leishmaniasis is classified as a neglected tropical disease but is endemic in several areas of the Mediterranean Basin, including Italy, where Leishmania infantum is most involved as the parasite, phlebotomine sand fly as the vector and dog as the principal reservoir. Effective surveillance of communicable infectious diseases is a goal worldwide for organisations such as the WHO and for local and national governments but is an unfulfilled objective. Even in Italy and particularly in the region of Tuscany, despite mandatory reporting, significant gaps each year are identified between reported cases and hospital admissions. By estimating the underreporting of confirmed human leishmaniasis cases, this protocol aims to suggest actions to strengthen the current epidemiological surveillance system to enable timely and effective public health intervention in human and veterinary populations.

This retrospective multicentre study, conducted in the Central Tuscany Health District, the most populous area of the Tuscany region with approximately 1.6 million inhabitants, is based on the analysis of data collected from 2014 to 2024 using diagnostic laboratory, hospital and regional information system sources. The primary objective is to estimate the degree of underreporting of leishmaniasis in this area through the application of capture-recapture models. The secondary objective is to analyse the clinical and demographic characteristics of individuals diagnosed as confirmed leishmaniasis cases between January 2014 and December 2024, as well as to perform a geolocation analysis of the cases. The study includes the entire population, both adult and paediatric, of the Central Tuscany Health District who underwent laboratory testing for leishmaniasis (serological tests identifying the presence of antibodies; parasitological examination with evidence of amastigotes in aspirates, smears or biopsy sections; culture examination of aspirates, biopsies and/or peripheral blood positive for the presence of promastigotes; identification of Leishmania nucleic acid in aspirates, biopsies and/or peripheral blood samples via molecular diagnosis).

The study is being conducted in accordance with the protocol approved by the Ethics Committee of the Tuscany Region – Pediatrics Section, in November 2024. Ethics Committee opinion register number: 219/2024. Because the study uses only pseudonymised, routinely collected administrative and laboratory data with no direct patient contact or intervention, individual informed consent was not required, as confirmed by the Ethics Committee. Findings will be submitted to a peer-reviewed journal, presented at international conferences and presented at stakeholder workshops.

The McMaster Monitoring My Mobility (MacM3) study aims to understand trajectories of mobility decline in later life using multisensor wearable technology. To our knowledge, MacM3 is the first major cohort to combine accelerometry and a Global Positioning System (GPS) to track real-world mobility in community-dwelling older adults.

Between May 2022 and May 2024, MacM3 recruited 1555 community-dwelling older adults (mean age 73.9 years, SD=5.5) from Hamilton and Toronto, Ontario. Of the cohort, 68.4% were female, 62.4% married/partnered, 75.3% had post-secondary education and 62.9% had≥3 comorbidities. Most were Canadian born (69.4%) and white/Caucasian (88.0%), with greater ethnocultural diversity observed at the Toronto site.

At baseline, 56.7% of participants reported no mobility limitations, 15.9% had preclinical limitations and 27.4% had minor mobility limitations. Mean gait speed for the total sample was 1.23 m/s, with a mean Timed Up and Go time of 9.4 s and a 5x sit-to-stand time of 13.0 s. A total of 1301 participants had valid wrist-worn device data, and 1008 participants who agreed to wear the thigh-worn device had valid data (≥7 days with ≥10 hours of wear per day). Step count data (n=1008) revealed a mean of 8437 steps per day (SD=2943), with 5073 steps in the lowest quartile and 12 303 steps in the highest.

Ongoing work aims to develop predictive models of mobility decline by integrating wearable, clinical and environmental data. Pipeline enhancements will enable GPS/inertial measurement unit fusion to explore mobility-environment interactions and support ageing-in-place tools.

Proactive and easily accessible interventions are needed to support people with long-term health conditions who experience limitations in activities of everyday life. However, there is a lack of interventions that promote self-management skills that prevent deterioration and improve health. The internet-based programme ‘Strategies for Empowering Activities in Everyday Life’ (SEE) supports people with long-term health conditions in developing self-management skills through knowledge, self-analysis and management strategies, promoting active and healthy daily life. This study protocol aims to evaluate the feasibility of SEE 2.0 and the study design.

This feasibility study employs a pretest and post-test design with no control group, embedded within a mixed-method approach. The participants will include 30–40 clients, occupational therapists and managers involved in delivering SEE 2.0 in primary healthcare and hospital-based services. Data will be collected through assessments and forms at baseline, 4 months and 12 months after inclusion. Additionally, qualitative methods will be used to enhance the understanding of participants’ experiences.

The study was approved by the Swedish Ethical Review Authority. The results will inform the refinement of SEE 2.0 and guide decisions on whether to proceed with planning a full-scale evaluation to assess the intervention’s effect. The results will be published in peer-reviewed scientific journals on websites and presented at conferences and seminars to reach various user groups.

NCT06484322.

Leishmaniasis poses a significant public health problem in Kenya, where effective case management and treatment rely on accurate diagnosis. This review aims to summarise the research landscape on leishmaniasis diagnostics in Kenya and identify gaps.

This scoping review expands a previously published scoping review on leishmaniasis in Kenya to further analyse studies focusing on diagnostics. The field of diagnostics was chosen because of recent pushes for novel tools and because of the role timely diagnosis plays in disease elimination. A comprehensive search of PubMed, Embase via Embase.com, Web of Science Core Collection, the Cochrane Library, ClinicalTrials.gov, WHO ICTRP and the Pan African Clinical Trials Registry was conducted, covering studies up to 5 January 2024.

After dual, blind screening with conflict resolution by a third reviewer, 41 studies were included in the review. These studies examined a range of diagnostic tools; however most were assessed in one or few studies, and none evaluated real-time PCR. Additional gaps in the research landscape include a lack of diagnostics for cutaneous leishmaniasis and post-kala-azar dermal leishmaniasis in Kenya, outdated literature surrounding the Direct Agglutination Test and randomised trials for any diagnostic tool.

Future research should focus on solidifying the validity and reliability of diagnostic tools in the Kenyan context and updating previous work.

Vector control is imperative for eliminating leishmaniasis as a public health problem in Kenya. As elimination efforts expand in East Africa, it is crucial to understand the current research landscape. To address that need and identify gaps, a scoping review was conducted to characterise the landscape of leishmaniasis vector research in Kenya.

Building on a previously published scoping review by this team, we updated database searches in PubMed, Embase via Embase.com, Web of Science Core Collection, the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) and the Pan African Clinical Trials Registry to incorporate literature up to 4 January 2024 and focused on vector-related papers. Studies classified as ‘prevention’ in the original scoping review were included due to overlapping definitions.

A total of 95 studies were included in the analysis. Although a wide range of sandfly species have been documented, most of the research is outdated, having taken place 20–40 years ago. Existing studies are mostly epidemiological with little focus on basic and clinical research. There are also no studies on post-kala-azar dermal leishmaniasis despite its potential contribution to the disease transmission cycle. The geographical scope of the research is largely limited to traditional transmission foci with little attention to new disease hotspots such as North Eastern Kenya.

These research gaps need to be addressed to better inform the country’s leishmaniasis prevention and vector control strategy.

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

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

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

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

NCT06386263.

Millions of patients receive general anaesthesia every year with either propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA). It is currently unknown which of these techniques is superior in relation to patient experience, safety and clinical outcomes. The primary aims of this trial are to determine (1) whether patients undergoing (a) major inpatient surgery, (b) minor inpatient surgery or (c) outpatient surgery have a superior quality of recovery after INVA or TIVA and (2) whether TIVA confers no more than a small (0.2%) increased risk of definite intraoperative awareness than INVA.

This protocol was co-created by a diverse team, including patient partners with personal experience of TIVA or INVA. The design is a 13 000-patient, multicentre, patient-blinded, randomised, comparative effectiveness trial. Patients 18 years of age or older, undergoing elective non-cardiac surgery requiring general anaesthesia with a tracheal tube or laryngeal mask airway will be eligible. Patients will be randomised 1:1 to one of two anaesthetic approaches, TIVA or INVA, using minimisation. The primary effectiveness endpoints are Quality of Recovery-15 (QOR-15) score on postoperative day (POD) 1 in patients undergoing (1) major inpatient surgery, (2) minor inpatient surgery or (3) outpatient surgery, and the primary safety endpoint is the incidence of unintended definite intraoperative awareness with recall in all patients, assessed on POD1 or POD30. Secondary endpoints include QOR-15 score on POD0, POD2 and POD7; incidence of delirium on POD0 and POD1; functional status on POD30 and POD90; health-related quality of life on POD30, POD90, POD180 and POD365; days alive and at home at POD30; patient satisfaction with anaesthesia at POD2; respiratory failure on POD0; kidney injury on POD7; all-cause mortality at POD30 and POD90; intraoperative hypotension; moderate-to-severe intraoperative movement; unplanned hospital admission after outpatient surgery in a free-standing ambulatory surgery centre setting; propofol-related infusion syndrome and malignant hyperthermia.

This study is approved by the ethics board at Washington University, serving as the single Institutional Review Board for all participating sites. Recruitment began in September 2023. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media.

NCT05991453.

Difficulty with walking can lead to reduced quality of life for people with Parkinson’s disease (pwPD); improving walking is considered a treatment priority. Drug therapies can control PD symptoms; however, pwPD often still experience mobility problems.

Functional electrical stimulation (FES) induces movement in weak muscles via external electrical stimulation. FES is used in stroke and multiple sclerosis patients to correct dropped foot by stimulating the common peroneal nerve and is associated with improved quality of life and mobility. The randomised feasibility study preceding this definitive study showed that daily FES can produce a clinically meaningful improvement in walking speed in pwPD; this was sustained 4 weeks after FES was withdrawn. STEPS II is the first definitive randomised controlled trial, with blinded outcome assessment, aiming to determine the efficacy of FES in pwPD.

STEPS II is a two-group, parallel, assessor-blinded, superiority randomised controlled trial with an internal pilot, designed to compare FES plus usual care versus usual care alone. 234 participants will be randomised across eight UK sites. Telephone pre-screening and face-to-face screening will determine eligibility. The intervention group will attend four unblinded FES visits to receive the device and assess walking with and without FES. All participants have blinded assessments at baseline and weeks 2, 6, 18 and 22. The primary objective is to compare whole body bradykinesia at 18 weeks post-baseline via changes in 10m walking speed. Secondary objectives will assess the wider effects of FES on Parkinsonian gait and quality of life. An embedded qualitative component will explore wider experiences of FES.

This study received ethical approval from the Yorkshire and The Humber-Sheffield Research Ethics Committee (reference 23/YH/0193). A Data Monitoring Committee and Trial Steering Committee will provide independent oversight. Dissemination will be via publications, conferences and social media. FES intervention and training materials will be made open access.

ISRCTN13120555.

To evaluate whether remdesivir is associated with cardiac adverse events (CAEs), addressing concerns raised by basic experiments, clinical case reports and observational studies.

Systematic review and meta-analysis.

MEDLINE and Embase, searched from January 2020 to December 2023.

Randomised controlled trials (RCTs) comparing remdesivir with placebo or standard care in patients with COVID-19, with a primary focus on cardiac safety.

We included RCTs that evaluated the safety of remdesivir in patients with COVID-19 . Eligible studies were those that compared remdesivir with placebo or standard care in adult patientsCOVID-19 . Inclusion criteria emphasised safety outcomes, particularly CAEs, as primary endpoints.

Two reviewers independently extracted data. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-Harms guidelines. Risk of bias (RoB) was assessed using the Cochrane Collaboration tool. A random-effects model was used for data synthesis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to assess the certainty of evidence. The primary outcome was the incidence of any CAEs, defined as a composite of all reported cardiac-related harms. Secondary outcomes included specific CAEs such as arrhythmias, heart failure and myocardial disorders.

We identified 1698 studies, of which seven RCTs met the inclusion criteria, comprising a total of 4566 participants. The RoB was assessed across multiple domains, with four RCTs showing low risk and three showing moderate risk in specific areas. Pooled analysis revealed no significant association between remdesivir use and CAEs (RR=0.84, 95% CI: 0.68 to 1.04, p=0.118). Subgroup analyses showed consistent findings across different patient demographics and comorbidities. GRADE assessment indicated moderate certainty for overall CAEs, low certainty for arrhythmias and heart failure (due to imprecision and study-level bias), and very low certainty for myocardial disorders (due to small sample size and indirectness).

Contrary to preliminary concerns and case reports, our meta-analysis found no evidence of a statistically significant association between remdesivir and CAEs among patients with COVID-19 . These findings provide reassurance to clinicians regarding the safety profile of remdesivir in this patient population, supporting its use as an antiviral therapy in the treatment of COVID-19. Further research is warranted to validate these findings and to clarify whether remdesivir may have a neutral or potentially protective effect on cardiac outcomes.

CRD42022383647.

Cardiovascular (CV) diseases are associated with adverse outcomes. However, attention has typically focused on outcomes considered relevant by doctors, whereas the potential gap in perception and relative importance of outcomes that may exist between patients and doctors has been scarcely explored. Evidence available reports the views of either patients or doctors alone, and data are analysed in aggregate. We investigated this issue by surveying for the first time patients’ and doctors’ opinions simultaneously, on a one-to-one basis.

Survey involving patients with different CV diseases. Each patient and their attending doctor were asked to simultaneously but independently gauge the importance each attached to a predetermined set of outcomes, filling out disease-specific questionnaires. Results were analysed by compositional analysis.

Inpatients and outpatients being seen by cardiologists and internal medicine specialists at hospitals affiliated with the National Health System in Umbria, Italy.

All-comer patients, presenting with one of the following conditions: atrial fibrillation (AF), myocardial infarction (MI), heart failure (HF) or considered at high CV risk.

Importance attached to outcomes relative to life path, quality of life, future clinical events.

From 337 paired questionnaires returned, significant differences between patients’ and doctors’ perspectives emerged. Specifically: (1) patients with AF were significantly less concerned about the risk of stroke than doctors; (2) worsening of HF was a greater concern for doctors than patients, whereas patients weighed the risk of disability more; (3) patients with a previous MI, or at high CV risk, weighed the risk of hospitalisation less relevant than doctors, but were significantly more concerned about the risk of disability.

Simultaneous, one-to-one assessment of patients’ and doctors’ opinion shows remarkable differences between patients’ perception and physicians’ judgement concerning the relevance of major CV outcomes. Appreciation and sharing of these issues may inform better tailoring of cardiac care.