Conectar
The Infant Gut Bacterial Study in Nigeria (INBUGS-NG) investigates how delivery mode, antibiotic exposure, feeding practices and environmental factors shape gut microbiome development and acquisition of antibiotic resistance genes (ARGs) during the first year of life in northern Nigeria.
Between February and July 2024, 90 mother–infant dyads were enrolled at a tertiary hospital in Kano city, Nigeria. This was a prospective longitudinal cohort with follow-ups at 10 scheduled time points: days 0, 1, 3, 5, 7, 14, 28, 90, 180 and 365. We also intensified stool sampling after infant antibiotic administration, enabling dense early-life sampling. To date, the cohort has contributed 480 infant stool samples, 232 maternal rectal swabs, 254 breast milk samples and 806 environmental samples (total 1772). In parallel, socio-demographic, clinical and cultural data were collected using Research Electronic Data Capture (REDCap) and household visit diaries.
Baseline data show that 84/90 mothers (93.3%) received postpartum antibiotics, and 26/90 infants (28.9%) received antibiotics within the first 3 months of life. Only 8% of infants were exclusively breastfed, with early water supplementation common. Caesarean deliveries accounted for 25% of births, and the mean gestational age was 38.5 weeks. Across the cohort, high retention was achieved, and the study has generated a unique long-read metagenomic resource from an African infant population, with analyses ongoing.
Shotgun long-read metagenomic sequencing (Oxford Nanopore) will enable strain-level and plasmid-level profiling of microbial communities and ARGs. Planned analyses include associations between early-life exposures and resistome dynamics, as well as cross-cohort comparisons with a parallel study in Pakistan. Follow-up will continue through 12 months.
This project, in adult surgical patients, will evaluate whether the creation of a customised checklist, driven by a clinical decision support tool, is able to improve anaesthesia providers’ adherence to consensus guidelines and standardised practice recommendations for the prevention of postoperative nausea and vomiting (PONV).
The intervention will be evaluated using a sequential, repeated crossover design at the institutional level, with designated washout, control and intervention periods. The surgical case will serve as the unit of analysis. The primary outcome is adherence to appropriate PONV prophylaxis administration guidelines. Secondary outcomes include the incidence of PONV and length of stay in the postanaesthesia care unit (PACU).
This protocol and statistical analysis plan provide an outline of the study design, primary and secondary end points and analytic approach. The Advancing Strategies to Optimise the PerIopeRativE Management of PostOperative Nausea and Vomiting trial has received approval from the Vanderbilt University Institutional Review Board (IRB: 250773). The results will be disseminated through peer-reviewed publications and presentations at national conferences. Findings from this trial will inform best practices for timely antiemetic prophylaxis, with the goal of reducing PONV incidence and shortening PACU stay.
Healthcare professionals are increasingly burdened by clerical tasks, contributing to reduced job satisfaction, heightened burnout and potential risk for patient safety. Despite ongoing efforts to promote patient-centred care, direct interaction time with patients remains limited, affecting both professional fulfillment and the quality of patient experience. In response, hospitals have begun implementing structured programmes to enhance protected patient time, though their effectiveness remains uncertain. The Geneva University Hospitals (HUG) developed the ‘More Time at Patients’ Side’ (MTP) programme, integrating Lean management and Design Thinking principles to optimise clinical interactions. This study aims to evaluate an MTP booster intervention, designed to reinforce selected programme elements, using a cluster-randomised controlled trial focusing on patient pain management and healthcare professional job satisfaction.
The MTP Booster will be implemented in selected units at HUG across internal medicine, surgery, rehabilitation, palliative care and paediatrics units. Originally launched in 2017, the MTP programme introduced structured medical rounds, delegated clerical tasks and communication tools such as patient whiteboards. The booster intervention follows a stepped-wedge cluster-randomised design, with immediate reactivation in intervention units and delayed implementation in control units. The intervention consists of two key components: (A) a collaborative selection of MTP elements to reinforce, based on their feasibility and perceived usefulness and (B) structured integration of audit and feedback into daily routines, including on-site observations and staff training. The primary outcome is the quality of pain management, measured by the timely administration of analgesia. Secondary outcomes include pain documentation, patient satisfaction, healthcare professional work satisfaction, burnout levels, turnover risk and absenteeism. Other MTP-related audits are suspended during the study to preserve methodological integrity, and concurrent institutional initiatives will be documented as potential confounders.
The trial has a declaration of no objection by Swissethics (2024-00169). All final results will be reported in accordance with the Consolidated Standards of Reporting Trials extended for cluster-randomised trials. We intend to publish the results of this trial in an international peer-reviewed journal, irrespective of the results.
The trial is currently in the pre-results stage and is registered at ClinicalTrials.gov, ID: NCT06491797, 9 July 2024.
Shared decision-making is widely advocated in policy and practice, but how it is to be applied in a high-stakes clinical decision such as major lower limb amputation due to chronic limb-threatening ischaemia or diabetic foot is unclear. The aim of this study was to explore the communication, consent, risk prediction and decision-making process in relation to major lower limb amputation.
A qualitative study (done as part of a broader mixed-methods study) using semi-structured interviews. Interview transcriptions were analysed using thematic analysis.
Vascular centres in three large National Health Service hospitals in Wales and England, UK, between 1 October 2020 and 30 September 2022.
A purposive sample of 18 patients for whom major lower limb amputation was considered as a treatment option/carried out, with interviews conducted before or within 4 months of amputation and 4–6 months after amputation. A further purposive sample of 20 healthcare professionals (including eight surgeons) involved in supporting or conducting major lower limb amputation decision-making.
Five major categories were identified that highlighted the challenges of ensuring shared decision-making associated with major lower limb amputation: (i) patients’ limited understanding, (ii) variable patient attitudes to decision-making, (iii) healthcare professionals’ perceived challenges to sharing decision-making, (iv) surgeons’ paternalism and (v) patients’ and healthcare professionals’ decisional regret/possible consequences of challenges.
Amputation is a life-changing decision for both patients and healthcare professionals, with huge consequences. Despite being considered the gold standard, our findings highlight several challenges to effective shared decision-making for major lower limb amputation. Shared decision-making training for healthcare professionals is paramount if these limitations are to be addressed and patients are to feel confident in being adequately informed about the treatment decisions that they make.
The implantable cardioverter defibrillator (ICD) is a cardiac device recommended for use to prevent the occurrence of sudden cardiac death (SCD) in post-myocardial infarction (MI) patients with reduced left ventricular ejection fraction (LVEF). The evidence informing this guidance comes from landmark trials that are now more than 20 years old. The risk-benefit profile of ICD for the contemporary target population may have changed substantially since then, which raises the question of whether there is evidence for sparing patients a procedure associated with potentially severe complications and high healthcare costs. A main part of the PRevention Of sudden cardiac death aFter myocardial Infarction by Defibrillator implantation (PROFID) project is the PROFID EHRA trial, which is supported by the European Heart Rhythm Association. PROFID EHRA is a European Union-funded, prospective, randomised, multi-centre, non-inferiority study designed to compare optimal medical therapy (OMT) alone to ICD with OMT, for post-MI patients with reduced LVEF. The study also describes economic evaluation methods to quantify the cost and health implications of using OMT alone in place of ICD implantation plus OMT in this group of patients.
The economic evaluation has been designed to conduct a pre-trial cost-effectiveness analysis (CEA) prior to the availability of trial data, followed by a within-trial cost-consequences analysis (CCA) and a long-term post-trial CEA, conducted from the National Health Service and Personal Social Service perspective in England. The pre-trial CEA uses simulation modelling informed by available evidence to assess the lifetime costs and quality-adjusted life years of OMT alone and ICD+OMT in post-MI patients with reduced LVEF at risk of SCD, as defined in the PROFID EHRA trial. The within-trial CCA is intended to summarise the health-related quality of life (HRQoL), healthcare resource use and associated costs observed during the PROFID EHRA trial follow-up period. The post-trial CEA updates the pre-trial model by incorporating contemporary evidence about the HRQoL and costs observed during the trial and the occurrence of those events and outcomes accruing during the trial follow-up period and projecting them into the expected lifetime of the patients. Sensitivity analyses are performed to assess the robustness of the CEA results with respect to both model assumptions and uncertainty in the value of the model input parameters. Finally, a value of information analysis will identify the key drivers of uncertainty surrounding the model conclusions regarding the optimal treatment strategy, establishing if further research may be required.
The PROFID EHRA trial, under legal sponsorship of Charité—Universitätsmedizin Berlin, Germany, received its first ethics approval by the Medicine Research Ethics Committee of the La Paz University Hospital in Madrid, Spain (reference number LHS-2019-0209). Before including patients, for all participating study centres, the required local, central and/or national ethical approval has to be obtained. As of the date 13 November 2025, at least one participating study centre in the following countries has received ethical approvals from relevant ethics committees: Austria, Belgium, Czech Republic, Denmark, France, Germany, Great Britain, Hungary, Israel, the Netherlands, Poland and Spain. Results will be shared with the general public through various media channels and additionally with healthcare professionals and the scientific community through scientific meetings, conferences and publications.
Minimally invasive endoscopic procedures constitute the cornerstone of first-line treatment for bulbar urethral strictures, although their long-term effectiveness is limited by high recurrence rates. The Optilume drug-coated balloon (DCB) is a novel intervention combining mechanical dilation with localised delivery of paclitaxel to reduce recurrence by inhibiting scar tissue formation. While its efficacy has been demonstrated in patients with recurrent strictures, its potential as a first-line option in treatment-naïve patients remains unexplored. The FIRST-CARE trial aims to assess the efficacy and safety of Optilume DCB compared with standard endoscopic treatment in treatment-naïve patients with bulbar urethral strictures.
Design: Two-arm, randomised, single-blind (participant), investigator-initiated, parallel-group, multicentre clinical trial. Patients: The study will enrol 140 adult male patients with treatment-naïve, single bulbar urethral strictures ≤3 cm in length. Interventions: All patients will undergo the assigned procedure under general anaesthesia with 1.5 g intravenous cefuroxime. Optilume group patients will receive ≥5 min balloon dilation with localised paclitaxel delivery. The control group will receive standard endoscopic treatment (eg, direct visual internal urethrotomy, laser or dilatation). In both groups, a 12–14 French Foley catheter will be left in place for 3–5 days. Primary outcome: Freedom from repeat intervention within 12 months of follow-up. Primary analysis: Time-to-event will be defined from the date of intervention to the date a repeat intervention is decided (indicated and planned) due to confirmed recurrence, with censoring at 12 months. Groups will be compared using Kaplan-Meier survival analysis and the log-rank test. Cox regression and modified Poisson regression will be used to estimate HRs and relative risks.
The trial is approved by the Danish National Committee on Health Research Ethics (2401370) and will be conducted in accordance with the Declaration of Helsinki and principles of Good Clinical Practice. In line with national guidelines, all eligible patients are counselled regarding available treatment options prior to enrolment. Results will be disseminated via peer-reviewed publications and scientific presentations.
Chronic dyspnoea is a prevalent symptom, and primary care is ideally placed to identify and manage it. However, chronic dyspnoea is under-reported by patients and can be a diagnostic dilemma for practitioners. A fully automated system of patient screening, coupled with a clinical decision support system (CDSS) that uses a validated and evidence-based dyspnoea algorithm, may improve detection, diagnosis and management of the condition. There is currently no CDSS validated for chronic dyspnoea diagnosis and management in primary care in Australia. The objectives of this study are to assess the clinical impact of a CDSS for chronic dyspnoea in primary care. We hypothesise that the use of the CDSS will lead to a clinically significant improvement in patient-reported dyspnoea scores, reduced time to diagnosis and healthcare costs at 12 months compared with standard care.
The BREATHE study is an open-label, cluster-randomised controlled trial of standard of care compared with a CDSS. General practices (n=40) in metropolitan, regional/rural and rural/remote settings will be recruited and randomised equally to pre-screening for chronic dyspnoea and usual standard-of-care management or pre-screening and CDSS-guided management. The CDSS includes an algorithm derived from a robust data and clinical knowledge model and incorporates evidence-based recommendations for the assessment and management of chronic dyspnoea. It is integrated into general practice medical software systems, fitting in the workflow of general practitioners (GPs). Eligible patients will be ≥18 years old and will have previously consented to receive SMS communication from their practice. In-scope patients will receive an automated text message prior to their GP appointment and will be screened for chronic dyspnoea (≥4 weeks). Patients identified with chronic dyspnoea will be invited to participate in the BREATHE study and followed up for 12 months. The primary outcome is improvement in the Dyspnoea-12 (D-12) score from baseline to 12 months, measured by the Dyspnoea-12 (D-12) questionnaire. Secondary outcomes include disease-specific questionnaires to assess changes in clinical outcomes, time to final diagnosis, quality of life, healthcare utilisation and costs incurred to patients.
The trial is registered at ANZCTR (ACTRN12624001451594). ANZCTR is a primary registry that meets the requirements of the ICMJE and is listed on the ICTRP Registry Network.
The study protocol has been approved by the University of New South Wales Human Research Ethics Committee (HREC) (iRECS6645) and complies with the National Health and Medical Research Council ethical guidelines. Participating practices and each GP will provide written, informed consent. All patients being screened will provide electronic informed consent. Results of the study will be disseminated through various forums, including peer-reviewed publications and presentation at national and international conferences. Following the study, participating practices will be provided with a summary of the findings of the study, together with a full copy of any publications and a plain language statement for participants, which will be made available in the practice reception area.
To test the feasibility of identifying and quantifying resource use for a Hospital-at-Home (HaH) model in Danish municipalities, we used a micro-costing approach. Additionally, we aimed to generate a transparent activity and time dataset. This dataset will support subsequent tariff development with time-driven activity-based costing and feed into the economic evaluation of an ongoing randomised controlled trial (RCT).
Prospective pilot feasibility study.
Three municipalities in the Central Denmark Region in collaboration with emergency department specialists and general practitioners.
56 elderly acute patients treated in HaH during the pilot phase.
Feasibility of micro-costing data collection (completeness, consistency and acceptability to staff) and descriptive resource-use quantities by activity and provider group. No price assignment or cost estimates are reported.
Patients received a mean of 3.8 HaH treatment days with 7.8 acute team visits and 3.9 municipal-staff visits per treatment course. The acute team spent a mean of 742 min per patient across treatment activities, communication, documentation and transport, while municipal care staff recorded a mean of 213 min. Intravenous medicine administration and vital sign assessments were the most frequent activities. Data completeness and consistency improved over time through co-design and feedback.
Detailed resource-use measurement using provider logs was feasible in a municipal HaH model and produced an activity and time dataset suitable for tariff development. Findings are context-specific and not generalisable due to the small sample. The micro-costing log refined through the pilot will be applied in an RCT, where time and activity data will be used to construct a tariff using time-driven activity-based costing.
The Veterans Health Administration (VA) integrated mental and physical health services to better detect and treat depression. Primary care nurses conduct screening annually. Clinicians, including Primary Care Mental Health Integration (PCMHI) specialists, follow-up as needed for treatment. Depression detection and management processes are complex, involve multilevel stakeholders, and are subject to significant disruption from COVID-19 and from the resulting expansion of telehealth, aiming to preserve care access. This study aimed to examine whether the COVID-19 pandemic worsened depression-related care quality and/or patient outcomes (eg, suicide).
Given hypothesised care disruption (lowered care quality) during COVID-19, we will first assess the VA population’s trajectory from a new positive depression (and suicide risk) screen to appropriate treatment (ie, medication, therapy) in the Fiscal Year 2019–2323. We will also examine the changing mix of virtual and in-person depression care delivered. Second, we will use interrupted time series analyses to explore the extent to which psychiatric emergency visits and hospitalisations may be mitigated by clinician detection of depression. As well as compare mental health-related mortality rates between patients detected and not detected to have depression. Subanalyses will reveal where (eg, clinics with low PCMHI access) and for whom (eg, minorities) detection does not systematically occur, and downstream negative sequelae, to guide future intervention. Finally, we will interview 40 veterans, half of whom were detected and half not detected to have depression and 40 VA primary care and PCMHI providers about changes brought on by the pandemic and the expansion of virtual care across three VA facilities. In addition to contextualising disrupted care findings, qualitative data will help identify best practices on patient-to-provider and provider-to-provider interactions in hybrid in-person/telehealth depression care models.
Ethics approval was granted by the VA Greater Los Angeles Healthcare System Institutional Review Board. Alongside journal publications, dissemination activities include briefings to our policy and operational partners, and presentations to clinical, research and policy-oriented audiences.
Post-COVID syndrome manifests with a diverse array of symptoms for which no standard care plan currently exists. Many questions were raised by patients, which underscored the need for a validated patient-reported outcome measure (PROM). Therefore, a post-COVID module was developed to be included in the Assessment of Burden of Chronic Conditions (ABCC-) tool. The ABCC-tool evaluates and visualises the perceived physical, emotional and social burden of one or multiple chronic disease(s) using a balloon diagram and aims to facilitate person-centred care and structured discussions between patients and healthcare professionals. This study explores the patients’ perspective on the content of the ABCC-tool for post-COVID and the tool’s usability in a home-based setting.
All patients who completed the ABCC-tool for post-COVID were invited for an online semi-structured interview. We selected post-COVID patients who had used the tool in the past three months. Interviews were audio recorded and analysed using a thematic approach with Atlas.ti version 23.
Nineteen post-COVID patients (10 males, mean age 56) were interviewed between May and August 2024. The tool was regarded as user-friendly, and patients indicated they would use the tool again in the future. Patients valued the tool’s broad range of topics, some of which are often overlooked in standard healthcare consultations. The tool was comprehensible and relevant according to all patients. The balloon diagram was easy to understand, but a legend explaining the colours of the balloons was preferred. Other suggestions for improvement included adding open-text fields and periodic reminders to increase usability and adding long-term data.
The ABCC-tool is a promising instrument for post-COVID patients, offering a structured way to monitor and communicate experienced burden in addition to standard healthcare consultations. Refinements addressing usability and comprehensiveness are recommended to facilitate its integration into clinical practices.
To explore and understand the disease priorities and preferences for rapid diagnostic testings (RDTs) among community members and stakeholders.
Qualitative study using focused group discussions and in-depth interviews. Thematic analysis was applied to identify themes of disease priorities and RDT preferences.
uMsunduzi Municipality, KwaZulu-Natal, South Africa.
49 community members and five community stakeholders were recruited through a combination of convenience and purposeful sampling using community events and meetings.
Participants prioritised both communicable diseases (HIV, tuberculosis) and non-communicable diseases (diabetes, cardiovascular disease, hypertension and cancer), aligning with national health priorities. They supported RDTs for early diagnosis and home-based testing to mitigate barriers to accessing diagnostic care. A need for post-test support, such as digital support tools, was also highlighted.
Community perspectives highlighted a demand for accessible, rapid and decentralised diagnostic tools for high-burden diseases in KwaZulu-Natal. RDTs have the potential to improve health outcomes and reduce health disparities through improved access to diagnostic healthcare services. The community members are potential end users of RDTs, especially in resource-constrained settings. Therefore, their perspectives should be considered in the development and implementation of RDTs to enhance acceptability and public health impact.
Infants born to pregnant women living with HIV (WLHIV) are at greater risk for morbidity and mortality and may also have poorer developmental outcomes as compared with infants who are not exposed to HIV. Nutrition interventions in pregnancy may affect developmental outcomes.
This study evaluated the effect of maternal vitamin D supplementation on infant development outcomes.
We conducted a secondary analysis of a randomised, triple-blind, placebo-controlled trial of maternal vitamin D supplementation from June 2015 to October 2019.
Antenatal care clinics in Dar es Salaam, Tanzania.
Pregnant WLHIV and their offspring.
Daily 3000 IU vitamin D3 or placebo supplements taken during pregnancy and lactation.
Infants were assessed for cognitive, language and motor development at 1 year of age with the Caregiver Reported Early Development Instruments (CREDI).
A total of 2167 infants were eligible, and 1312 of them completed CREDI assessments at 1 year of age. Vitamin D supplementation had no effect on overall CREDI z-scores (standardised mean difference (SMD) 0.03, 95% CI –0.09, 0.15, p value 0.66). There was also no evidence of a difference between vitamin D and placebo groups in language (SMD 0.06, 95% CI –0.08, 0.21, p value 0.40), motor (SMD 0.02, 95% CI –0.09, 0.14, p value 0.69) or cognitive domain z-scores (SMD 0.05, 95% CI –0.08, 0.17, p 0.48).
Maternal vitamin D supplementation during pregnancy and lactation did not affect infant development outcomes.
ClinicalTrials.gov identifier: NCT02305927.
Photobiomodulation therapy (PBMT), particularly when combined with a static magnetic field (PBMT-sMF), is a promising non-pharmacological approach for managing musculoskeletal disorders. However, high-quality evidence for its efficacy in lateral epicondylitis remains limited.
The study aims to investigate the effectiveness of PBMT-sMF vs placebo in reducing pain, improving function and modulating inflammatory markers in individuals with lateral epicondylitis.
Multicentre, randomised, triple-blinded, placebo-controlled trial.
Three outpatient physiotherapy clinics in Brazil.
50 adults (18–50 years) with unilateral lateral epicondylitis and baseline pain ≥50 on the visual analogue scale (VAS).
Participants received either active PBMT-sMF (n=25) or placebo (n=25), 2 times per week for 3 weeks. PBMT-sMF involved multi-wavelength irradiation at 4 epicondyle sites (60 s; 27.1 J/site). The placebo group underwent the same procedure without active irradiation.
The primary outcome was degree of pain rating (VAS). Secondary outcomes included forearm disability (Patient-Rated Tennis Elbow Evaluation, PRTEE), grip strength, serum tumour necrosis factor-alpha (TNF-α) levels and treatment satisfaction. Assessments were conducted at baseline, post-treatment (3 weeks) and at 4-week follow-up.
PBMT-sMF yielded a higher responder rate (defined as the proportion of participants achieving at least a 30% reduction in pain intensity relative to baseline) than placebo (72% vs 40%, p=0.045), with a clinically and statistically significant between-group difference. Compared with placebo, the PBMT-sMF group showed significantly greater reductions in pain intensity both at the end of treatment (51.4±19.8 vs 36.9±22.6; p=0.0223) and at follow-up (37.4±24.1 vs 20.3±21.2; p=0.0049). TNF-α levels also decreased significantly in the PBMT-sMF group compared with placebo at both time points (p
PBMT-sMF significantly reduced pain intensity and TNF-α levels, suggesting an anti-inflammatory mechanism. Although functional outcomes were not improved, PBMT-sMF may be a valuable short-term, non-invasive option for lateral epicondylitis pain management.
NCT04829734 on ClinicalTrials.gov
Postpartum depression (PPD) is a debilitating condition affecting over 20% of postpartum women, with disproportionately higher rates among black and Latina women compared with their white counterparts. Current recommendations for PPD prevention demand significant healthcare system resources, highlighting the need for alternative, evidence-based interventions that minimise strain on these systems. Mindfulness has been shown to effectively reduce depressive symptoms and prevent relapse across various populations. However, no studies to date have evaluated the efficacy of a digitally delivered mindfulness intervention specifically for black and Latina women at increased risk of PPD.
This article presents the protocol for the Healthy Mama and Baby study, a randomised controlled trial (RCT). This trial evaluates whether a mobile-based (mHealth) mindfulness intervention tailored for pregnant women reduces depressive symptoms among pregnant black and Latina women at high risk for PPD.
We are conducting a fully remote RCT, recruiting 600 pregnant black and/or Latina women at risk of PPD from Kaiser Permanente Northern California (KPNC), an integrated healthcare delivery system. Participants are enrolled before 30 weeks’ gestation. They are randomised into either an mHealth mindfulness intervention arm, which receives access to a mindfulness app tailored specifically for pregnant and postpartum women, or a time-matched and attention-matched active control arm, which receives access to an online program of calming nature sounds. Both arms are instructed to engage in their assigned program for 5–20 min per day for 6 weeks. Outcome assessments are conducted online at baseline, post intervention and post partum (~7 weeks post partum) using validated questionnaires. Outcomes include depressive symptoms (primary) and anxiety, sleep and perceived stress (secondary).
All study procedures have been approved by the KPNC Institutional Review Board. The findings will be disseminated widely through peer-reviewed publications and conference presentations.
People identified as higher risk by a machine learning algorithm (Future Innovations in Novel Detection of Atrial Fibrillation [FIND-AF]) are at increased risk of cardio-renal-metabolic-pulmonary disease and cardiovascular death. The OPTIMISE-1 randomised controlled trial aims to test the effect of community-based specialist-led identification and management of cardio-renal-metabolic-pulmonary (CRMP) disease and risk factors compared with usual care on the use of therapeutic interventions over a follow-up of 6 months among high FIND-AF risk community-dwelling individuals.
OPTIMISE-1 is a multicentre, pragmatic, prospective, randomised, open-label, blinded-endpoint strategy trial that will recruit 138 participants aged 30 years or older, with a high FIND-AF risk score and previously enrolled in the FIND-AF pilot study (NCT05898165), to be randomised 1:1 to a specialist-led care intervention or usual care. The primary endpoint is a composite of initiation or increase of guideline-directed CRMP therapies. The secondary endpoints are the components of the primary endpoint, time to primary endpoint, diagnosis of new CRMP diseases or risk factors, time to diagnosis of new CRMP diseases or risk factors, initiation or increase of guideline-directed CRMP therapies for participants with recorded CRMP disease, initiation or increase of guideline-directed CRMP therapies for participants with newly diagnosed CRMP disease and change in participant-reported quality of life.
The study has ethical approval (the North East & North Tyneside 2 Research Ethics Committee reference 24/NE/0188). Findings will be announced at relevant conferences and published in peer-reviewed journals in line with the Funder’s open access policy.
Clinicaltrials.gov NCT06444711.
Progressive supranuclear palsy (PSP) is a devastating neurodegenerative disease characterised by cognitive, behavioural and motor problems. Motor symptoms are highly disabling, while cognitive and behavioural changes have a major impact on carer burden, quality of life and prognosis. Apathy and impulsivity are very common, often coexistent in PSP, and negatively predict survival. In preclinical models and other diseases, apathy and impulsivity are associated with noradrenergic deficits, which can be severe in PSP.
Noradrenaline for Progressive Supranuclear Palsy Syndromes trial is a randomised, double-blind, placebo-controlled, crossover design, Phase IIb clinical trial to evaluate the efficacy and safety of oral atomoxetine for the treatment of cognitive and behavioural changes in PSP. Participants receive atomoxetine 40 mg (10 mg/mL oral solution) once daily or a matched placebo solution, in random order, each for 8 weeks. An ‘informant’, who knows the patient with PSP well, is co-recruited to complete some of the trial outcome measures. Participants remain in the trial for 22 weeks after randomisation. The primary objectives are to assess (1) safety and tolerability and (2) efficacy versus placebo on challenging behaviours as reported in a subscale of the Cambridge Behavioural Inventory. Secondary and exploratory measures relate to cognition, the PSP Rating Scale, mood and potential baseline predictors of individual response to atomoxetine computed from imaging, genetic and cognitive measures at baseline.
The trial was approved by the South Central-Oxford B Research Ethics Committee (REC) and the Medicines and Healthcare products Regulatory Agency (REC reference: 20/SC/0416). Dissemination will include publication in peer-reviewed journals, presentations at academic and public conferences and engagement with patients, the public, policymakers and practitioners.
ISRCTN99462035; DOI:
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.
Maintaining a healthy workforce is crucial for safe, high-quality care. To enhance well-being and engagement in Dutch university medical centres (UMCs), an overview of staff well-being and job perceptions is needed first. Surveys are widely used to improve working conditions, but varying questionnaires hinder a comprehensive view. This study aimed to evaluate the content of employee surveys currently used in UMCs in the Netherlands from a well-being perspective and to analyse the survey results at a national level.
All seven UMCs were approached to participate in the study and share employee survey data. The primary outcome of interest is work experience; a secondary analysis was conducted. Items were categorised following the Job Demands-Resources model. Descriptive statistics were presented as percentages, means and medians with IQRs.
Two UMCs participated and 31 862 completed surveys were included. Variation in survey items (eg, 15–18 subcategories, 21–33 question items), response options (eg, 1–5, 1–10), frequency (1–3 times per year) and timing were found. Scores on the following outcomes are presented: work overload, coworker support, job control, organisational justice, participation in decision-making, performance feedback, possibilities for learning and development, recognition, task variety, team atmosphere, team effectiveness, trust in leadership, other job resources, connecting/inspiring leadership, self-efficacy, goal-directiveness, boredom, burnout, job satisfaction, work engagement, other employee well-being, commitment organisation/team and work ability. Results should be interpreted with caution, and solely found for hospital A, for certain job control items, median scores of 2 or 3 were observed, whereas the majority of other question items revealed a median score of 4.
There is a significant lack of cohesion across employee surveys. As it stands, employee surveys in Dutch UMCs are not effective tools for monitoring the work experience or well-being of the healthcare workforce. While these surveys may support management decisions, this support is not reflected in interventions related to work and the work environment.
FreshRSS 