Conectar
Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a significant procedural adverse event (AE), occurring in 5–15% of cases and leading to substantial morbidity and mortality. Aggressive prolonged intravenous (IV) fluid regimens have demonstrated efficacy in reducing PEP in clinical trials. However, these regimens typically involve continuous infusion of IV fluids over 8–24 hours following ERCP, making them impractical for outpatient settings. Data on shorter hydration protocols are lacking. The STRIPE study aims to address this gap by evaluating short-term peri-procedural IV fluid regimens as a practical alternative for mitigating PEP.
This proof-of-concept, parallel-arm, randomised controlled trial will evaluate the impact of various short-term IV fluid regimens on post-ERCP serum amylase levels, a surrogate marker for PEP. Participants undergoing ERCP will be randomised into five groups, receiving 500 mL, 1000 mL, 1500 mL, 2000 mL or 2500 mL of IV Ringer’s lactate during the peri-procedural period. Patients, endoscopists and outcome assessors will be blinded to treatment allocation during the peri-procedural period. The primary outcome is the serum amylase level 24 hours post-ERCP. Secondary outcomes include PEP, 30-day AEs and unplanned healthcare encounters including those related to volume overload or cardiovascular AEs, duration of hospitalisation (for inpatients), death within 30 days and other relevant laboratory markers at 24 hours. A total of 505 participants (101 in each arm) will be enrolled to ensure adequate power after accounting for attrition and/or sample loss.
This trial was registered on clinicaltrials.gov on 7 February 2024. The study was approved by the University of Calgary Conjoint Health Research Ethics Board (REB23-0625). On study completion, data will be made available on reasonable request to the corresponding author after completion of the study. Study dissemination and knowledge translation is planned via presentations at scholarly meetings, publications in peer-reviewed journals and, ideally, via adoption of results into clinical practice guidelines.
Randomised clinical trials (RCTs) are gold standard in evidence-based medicine, but follow-up typically relies on clinic visits and trial-specific data collection. Much of this information overlaps with routinely collected healthcare systems data (HSD), such as electronic health records and national registries. Leveraging HSD for trial follow-up has the potential to reduce cost, time and resource burden. However, concerns remain about data quality and evidence is needed to show that HSD-based outcomes are reported to an equivalent standard to trial-specific data.
The Blood Cancer Clinical Trials Long-term Follow-up Using Integrated Healthcare Systems platform will link data collected from multiple myeloma clinical trials with HSD to create a research database supporting extended follow-up and further methodological and clinical research.
This data-linkage study includes participants from multiple myeloma RCTs conducted by the University of Leeds between 2008 and 2021. NHS (National Health Service) England will link these participants to HSD, including deaths and cancer registrations, systemic anticancer therapy, radiotherapy and Hospital Episode Statistics.
We will compare trial-collected outcomes with those derived from HSD, including mortality, treatment, second cancer incidence and major adverse events. Long-term overall survival will be estimated using national mortality data. HSD-derived demographic and clinical variables will be used to assess population representativeness relative to the wider myeloma population. Time to next treatment will be derived and evaluated as a surrogate for progression-free survival. HSD-derived frailty measures will be examined for prognostic utility, and radiotherapy and hospital records will be analysed to characterise bone-related treatments and skeletal complications.
Ethical approval has been obtained from the East of England–Cambridge Central Research Ethics Committee, with Section251 support from the Health Research Authority on advice from the Confidentiality Advisory Group. Findings will be disseminated through publications, conference presentations and engagement with stakeholders and patient groups.
Treatment for high-risk locally advanced prostate cancer typically includes radiation or radical prostatectomy plus androgen deprivation therapy (ADT), but the optimal use of neoadjuvant and adjuvant ADT in practice remains unclear. Relugolix and enzalutamide have demonstrated strong efficacy independently in the setting of advanced disease, but their combined use in neoadjuvant/adjuvant therapy has not been studied. This trial investigates their safety and efficacy as neoadjuvant/adjuvant therapy in patients undergoing definitive local treatment.
Relugolix and Enzalutamide as Neoadjuvant/Adjuvant to Local-regional treatment in Patients with High-risk, Locally Advanced Prostate Cancer (RENAPCA) is a prospective, single-arm, open-label phase Ib trial with blinded outcome assessment. The study is conducted across four tertiary oncology centres within the United States. Eligible participants are adult men with pathologically confirmed locally advanced high-risk prostate cancer who are candidates for definitive local therapy. Patients with significant comorbidities or a life expectancy of less than 6 months are excluded. The trial includes a 3+3 dose-escalation safety lead-in cohort (up to 12 patients) to determine dose-limiting toxicities and recommended phase 2 dose, followed by a dose expansion cohort (up to 46 patients). Interventions consist of 6 months of neoadjuvant therapy with relugolix plus enzalutamide, definitive local therapy (radical prostatectomy or radiation therapy), and 18 months of adjuvant therapy with relugolix plus enzalutamide. Primary outcomes include pathologic CR rate and minimal residual disease rate. Secondary outcomes include prostate-specific antigen response, progression-free survival, objective response rate, frequency and severity of adverse events, and positive margin/pathologic downgrade rate. Exploratory objectives include patient-reported outcomes and quality of life measures. RENAPCA will assess the safety and efficacy of neoadjuvant/adjuvant relugolix+enzalutamide in high-risk, locally advanced prostate cancer to support future larger-scale studies and potentially improve treatment outcomes.
This research protocol has been approved by the Institutional Review Board of the University of Oklahoma Health Sciences Center (7 March 2024). The study is based on voluntary participation with informed written consent.
Research on psychosocial interventions for dementia demonstrates increased rigour and robustness. However, if we are to influence practice, beyond results from randomised controlled trials, a variety of types and sources of evidence is needed. The Medical Research Council (MRC) framework offers a valuable guide for developing, evaluating and implementing complex interventions, to facilitate integration of research into practice. There is limited knowledge of how researchers design, evaluate and implement psychosocial intervention studies in dementia, using the MRC framework. This scoping review aims to: (1) identify the methodological and methods trends, use and gaps in the development, evaluation and implementation of psychosocial interventions for dementia, and (2) determine if and how the MRC six core elements were considered and applied in studies.
Six databases (Ovid MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, Cochrane Library) will be searched for studies published from 2015 (when MRC process guidance was published) to 2025. Identified deduplicated citations will be imported into Covidence software, where up to 40% of title/abstracts will be double screened by independent reviewers. ASReview will be used to rank articles by relevance, with a stopping criterion of 250 consecutive irrelevant articles. Full texts will be reviewed by a single reviewer and those excluded will be checked by a second reviewer. Data extraction will include study aim/objective (ie, to develop/adapt; test feasibility/pilot; evaluate; implement); methodology and methods applied; information on which MRC six core elements were considered (yes/no), and if so, how they were addressed (ie, qualitative details). A narrative synthesis, alongside graphical representations (eg, table/bar charts/histograms), will be used to synthesise findings on methodologies and methods mapped onto the MRC framework.
This secondary analysis scoping review does not require ethics approval. Results will be disseminated through peer-reviewed publication(s), seminars, webinars, conferences, postgraduate dementia programmes, blogs, commissioner briefings and social media. The findings will provide a state-of-the-art overview of current practices; advance methods/methodology such as informing a Delphi consensus study on appropriate research approaches; and guide researchers in application of the MRC framework to widen the scope of dementia care evidence for practice improvements.
Submitted to Open Science Framework https://doi.org/10.17605/OSF.IO/S56NQ.
Exercise therapy is the most recommended treatment for chronic low back pain (LBP), with evidence supporting modest effects, likely due to the heterogeneity of patient presentations. Evidence suggests that matching individuals to the most appropriate exercise type could improve outcomes. Systematic reviews also emphasise that effective exercise interventions should be patient centred, target paraspinal muscle health and be of sufficient duration. This study addresses these gaps using a targeted care approach to identify a homogenous sample that is more likely to respond to our interventions. The inclusion of a sample with predominant nociceptive pain profile will be performed with the integration of the Pain and Disability Drivers Management Model (PDDM) and the Lumbar Spine Instability Questionnaire (LSIQ). The primary aim of this two-arm randomised controlled trial is to compare the effectiveness of motor control plus isolated lumbar extension exercises (MC+ILEX, arm 1) to free-weight resistance training (arm 2) in reducing LBP-related disability. Secondary aims include examining whether changes in multifidus composition mediate disability improvements comparing intervention effects on muscle size and quality, strength, mobility, pain, quality of life, sleep, physical activity and satisfaction; exploring baseline LSIQ scores and sex/gender as moderators of treatment response; and investigating participants’ perceptions and experiences of exercise therapy.
A total of 106 participants will be recruited through primary and secondary care and randomised (1:1) to receive either MC+ILEX or free-weight resistance training. Both groups will complete 48 exercise sessions over 16 weeks. The primary outcome will be disability at 16 weeks, measured by the Oswestry Disability Index. Secondary outcomes include multifidus muscle composition and size, lumbar and gluteal muscle strength, hip range of motion, pain, physical and mental function, satisfaction and recovery, health-related quality of life, sleep quality and physical activity levels. Linear mixed-effects models will be used to assess primary and secondary outcomes. Regression analyses will explore whether baseline LSIQ scores moderate treatment effects on multifidus composition and other outcomes. A subsample of participants will undergo semistructured interviews before and after the intervention to explore their illness perceptions, illness mindsets, perceptions of exercise therapy, as well as their experiences and satisfaction with the two exercise interventions. Reflexive thematic analysis will be used to analyse qualitative data.
This study received ethics approval from the Central Ethics Research Committee of the Quebec Minister of Health and Social Services (CCER-25-26-14). Results will be submitted to peer-reviewed journals and scientific meetings.
Pulmonary embolism (PE) is a potentially fatal condition requiring timely diagnosis and treatment. CT pulmonary angiography (CTPA) is the gold standard for diagnosis and indicates PE severity through radiological markers of right heart strain. However, accurate interpretation and communication of these findings is often suboptimal in real-world practice. Artificial intelligence (AI) could alleviate pressure on radiology services by supporting PE identification, risk stratification and worklist prioritisation. Before widespread adoption, AI tools must be rigorously validated for diagnostic accuracy, safety and clinical impact.
This pragmatic single-centre, non-randomised quasi-experimental study will evaluate the diagnostic accuracy, feasibility, and clinical-cost impact of AI-assisted PE detection and risk stratification using AIDOC and IMBIO software. We will recruit two consecutive cohorts of adult patients undergoing CTPAs for suspected PE: a comparator cohort (12 months pre-AI implementation) and an intervention cohort (12 months post-AI implementation). AI will be applied retrospectively to the comparator cohort, while in the intervention cohort, radiologists will have contemporaneous access to the AI’s interpretation of CTPA images.
A subset of retrospective scans, both PE-positive and PE-negative, will undergo expert thoracic radiologist review to establish a reference standard. Data on patient demographics, clinical management and outcomes will be collected. Clinical management pathways and patient outcomes will be compared between cohorts to assess AI’s influence on acute PE management. Health economic modelling will assess the cost-effectiveness of integrating AI technology within the diagnostic workflow of acute PE.
This study was approved by the UK Healthcare Research authority (IRAS 311735, 10 May 2023). Ethical approval was granted by West of Scotland Research Ethics Service (23/WS/0067, 3 May 2023). Results will be shared with stakeholders, presented at national and international conferences, and published in open-access peer-reviewed journals.
To determine the safety and efficacy of ruxolitinib (RUX) and fostamatinib (FOS) compared with standard of care (SOC) in patients requiring hospital admission for the treatment of COVID-19 pneumonia.
Adaptive multiarm, multistage, randomised, open-label trial (three arm, two stage).
Five hospitals in England between October 2020 and September 2022.
Hospitalised patients (≥18 years) with COVID-19 pneumonia defined by a modified WHO COVID-19 severity grade of 3 or 4.
Participants were randomly assigned 1:1:1 to receive RUX (10 mg two times per day for 7 days then 5 mg two times per day for 7 days), FOS (150 mg two times per day for 7 days then 100 mg two times per day for 7 days) or SOC.
Primary outcome was development of severe COVID-19 pneumonia (modified WHO severity grade≥5) within 14 days of randomisation. Secondary outcomes included mortality, invasive and non-invasive ventilation, venous thromboembolism, duration of hospital stay, readmissions, inflammatory markers and serious adverse events (SAEs).
At stage 1, 181 patients were randomised, with 4 assessed as ineligible post randomisation. FOS was stopped early for futility with 16 participants (27.6%, n=58) developing severe COVID-19 pneumonia compared with 15 (25.0%, n=60) in the SOC arm (adjusted odds ratio (aOR) compared with SOC: 1.12; 95% CI 0.49 to 2.58; p=0.608). RUX progressed to stage 2 but the trial was stopped early due to slow recruitment. At the final analysis, 10 participants (16.1%, n=62) developed severe COVID-19 pneumonia in the RUX arm compared with 15 (24.6%, n=61) in the SOC arm (aOR: 0.63; 95% CI 0.25 to 1.57; p=0.161). Four (7.4%) participants in the FOS arm, none in the RUX arm and three (5.5%) in the SOC arm died within 14 days of randomisation. Infections were the most frequently reported SAE and were numerically higher in the FOS (10, 17.2%) and RUX (10, 16.1%) arms compared with SOC (7, 11.5%). Two unexpected serious adverse reactions occurred in the RUX arm only.
We found no evidence that FOS was superior to SOC for the treatment of COVID-19 pneumonia in patients requiring hospital admission. Due to early stopping, the trial was underpowered to establish RUX’s effect in this population. Further study is needed.
NCT04581954; EUDRA-CT:
Functional seizures (FS) are events that resemble epileptic seizures, but are not attributed to brain pathology and are instead thought to be due to psychological factors. A small, multisite, open-label, single-arm, pilot trial of a breathing intervention known as breathing control training (BCT) found it to be safe and effective in reducing seizure frequency in FS. We propose a protocol for a study to confirm these results.
A 24-week, multicentre, individually-randomised, assessor-blinded, two-arm, parallel-group efficacy and acceptability trial of BCT versus control (Befriending) in 220 participants ≥16 years of age with FS. Eligible participants will be randomly allocated to receive two sessions of either BCT or Befriending over a 4-week period. Sessions will be delivered by a respiratory physiotherapist at a clinical care site or via telehealth. They will complete assessments prior to commencing treatment and at 4, 12 and 24 weeks after their initial session of BCT/Befriending. The trial will be conducted alongside treatment as usual. An economic evaluation including cost-utility and cost-effectiveness analyses will be carried out from health sector and societal perspectives.
The study has been approved by The Austin Health Human Research Ethics Committee (HREC/84335/Austin-2022) and the New Zealand Central Health and Disability Ethics Committee (2022 FULL 12324). Findings will be reported to trial participants and consumers; presented at local, national and international conferences; and disseminated by a peer-reviewed scientific journal.
Medication non-adherence in older adults with long-term conditions contributes to significant morbidity, mortality and healthcare costs. While adherence support tools exist, many interventions fail to reach those most at risk. Automated medication dispensers (AMDs) show promise in improving adherence and health outcomes, but their integration into routine community pharmacy practice remains underexplored. This study aims to assess the effectiveness of an AMD intervention with SMS reminders in enhancing medication adherence among older adults and to evaluate how this technology can be integrated into community pharmacy workflows.
This randomised controlled trial involves 144 participants recruited from eight community pharmacies who will be randomised to receive either the AMD intervention or usual care. Primary outcomes include medication adherence, measured through pharmacy records and self-report at baseline, 3 and 6 months. Secondary outcomes include Morisky Medication Adherence Scale, health-related quality of life (SF-12), and healthcare resource use. A nested mixed methods process evaluation will explore uptake, acceptability and implementation.
The study protocol has been approved by the University of Bedfordshire Institute for Health Research Ethics Committee (IHREC1039), the NHS and the local authority Research Governance and Research Ethics Committee (NHS REC reference: 25/EE/0026). The findings will be disseminated via a final report, peer-reviewed journal publications and presentations at relevant conferences.
Most patients with health conditions necessitating time off work consult in primary care. Offering vocational advice (VA) early within this setting may help them to return to work and reduce sickness absence. Previous research shows the benefits of VA interventions for musculoskeletal pain in primary care, but an intervention for a much broader primary care patient population has yet to be tested. The Work And Vocational advicE feasibility study tested patient identification and recruitment methods, explored participants’ experiences of being invited to the study and their experiences of receiving VA.
A mixed method, single arm feasibility study comprising both quantitative and qualitative analysis of recruitment and participation in the study.
Primary care.
The study included participant follow-up by fortnightly Short Message Service text and 6-week questionnaire. Stop/go criteria focus on recruitment and intervention engagement. The semistructured interviews explored participants’ experiences of recruitment and receipt and engagement with the intervention.
19 participants were recruited (4.3% response rate). Identification of participants via retrospective fit-note searches was reasonably successful (13/19 (68%) identified), recruitment stop/go criteria were met with ≥50% of those eligible and expressing an interest recruited. The stop/go criterion for intervention engagement was met with 16/19 (86%) participants having at least one contact with a vocational support worker. Five participants were interviewed; they reported positive experiences of recruitment and felt the VA intervention was acceptable.
This study demonstrates that delivering VA in primary care is feasible and acceptable. To ensure a future trial is feasible, recruitment strategies and data collection methods require additional refinement.
We surveyed authors of publications in high-impact psychiatry journals to assess the (1) proportion that disseminated results to study participants or others with lived experience, and, among those who disseminated, (2) methods (eg, email) and (3) tools (eg, plain-language summary) used.
Meta-research review.
PubMed search on 14 December 2022 and emails to study authors for information on dissemination.
Eligible studies collected primary human data and were published in psychiatry journals with 2021 impact factor ≥10.
Study information was extracted by one investigator and validated by a second investigator, with conflicts resolved by consensus, with a third investigator consulted as necessary. We emailed authors approximately 2 years post-publication to ensure sufficient time had passed to share results. We estimated the proportion of authors that may have disseminated results to participants or others with lived experience, assuming that non-respondents (1) did not disseminate, (2) were half as likely to disseminate as respondents or (3) disseminated in the same proportion as respondents.
Of 141 studies, 94 (67%) authors responded. Among respondents, 21 (22%) reported disseminating to study participants, and an additional 9 (10%) reported disseminating lay materials to people with lived experience (total of 30 studies, 32%). Overall, we estimated that 15% (95% CI 10% to 22%) to 23% (95% CI 17% to 30%) of authors may have disseminated results directly to study participants and 21% (95% CI 15% to 29%) to 32% (95% CI 25% to 40%) to participants or others with lived experience. Among the 30 that reported disseminating, the most common methods were sending mail or emails to study participants (17 studies, 57%) and posting on social media (15 studies, 50%). The most common tools were plain-language summaries (22 studies, 73%) and webinars or other meetings (15 studies, 50%).
Dissemination of results to participants in mental health research is uncommon. Funding agencies, ethics committees, journals and academic institutions should support dissemination.
To assess the comparative effectiveness of educational interventions in neurological disease for healthcare workers and students.
Systematic review.
Medline, Embase and Cochrane through to 1 June 2025.
Studies evaluating neurological disease educational interventions with a comparator group (observational cohort/randomised controlled trial (RCT)) were included.
A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review was conducted (PROSPERO: CRD42023461838). Knowledge acquisition and educational methodologies were collected from each study. Study outcomes were classified using the Kirkpatrick and Kirkpatrick four-level model (learner reaction, knowledge acquisition, behavioural change, clinical outcome).1 Risk of bias was assessed using the Newcastle-Ottawa scale for non-randomised studies and the Cochrane Risk of Bias tool for RCTs.2 3
A total of 67 studies involving 4728 participants were included. Of these, 36 were RCTs, and 31 were observational studies. Virtual interventions were the most common (67.2%, n=45 studies), primarily targeting either medical students (46.3%, n=31 studies) or specialists (40.3%, n=27 studies). Overall, 70.1% (n=47) of studies demonstrated outcomes in favour of the intervention. However, few studies used K&K level 3/4 outcomes, with two studies evaluating behaviour change (level 3) and three assessing clinical outcomes (level 4 combined with other levels). No study exclusively assessed level 4 outcomes. Meta-analysis of 22 RCTs with calculable standardised mean differences (SMDs) (n=1748) showed a significant benefit of interventions (SMD 0.75, 95% CI 0.22 to 1.27, p=0.0056).
This review highlights a growing body of research particularly focusing on virtual techniques, specialist audiences and treatment-oriented content. Few studies assessed changes in practice or patient care. Non-specialists remain underrepresented. Future studies should prioritise assessing the clinical impact of educational interventions within non-specialist audiences.
Dysregulated immunity may account for an increased risk of infection and other adverse outcomes among frail hospitalised persons. The primary objective of this study is to examine whether baseline frailty is associated with the risk of developing ventilator-associated pneumonia (VAP) or other intensive care unit (ICU)-acquired infections among invasively ventilated adults. Additional objectives are to examine the relationship between frailty and hospital length of stay, discharge to a long-term care facility and vital status. We hypothesise that persons with frailty compared with others would have an increased risk of VAP and other infections, a longer hospital stay, higher probability of discharge to a long-term care facility and higher mortality.
This is a preplanned secondary analysis of the PROSPECT trial (
Participating hospital research ethics board approved the PROSPECT trial and data collection. The protocol for this study was approved by the Hamilton Integrated Research Ethics Board on 20 August 2015 (Project ID:19128). This study will identify whether frailty is associated with risk of VAP and other healthcare-associated infections in invasively ventilated patients, adjusted for other baseline factors. Results may be useful to patients, their caregivers, clinicians and the design of future research. Findings will be disseminated to investigators at a meeting of the Canadian Critical Care Trials Group. We will present study results at an international conference in the fields of critical care and infectious diseases, to coincide with or precede open-access peer-review publication. To aid knowledge dissemination, we will use a variety of formats. For example, for traditional and social media, we will create two different visual abstracts and infographics of our results suitable to share on clinician-facing and public-facing platforms.
Economic evaluations in healthcare can guide practice and inform policy. The objective of this paper is to present the protocol for a health economic evaluation comparing the cost-effectiveness of prophylactic treatment using pantoprazole 40 mg daily compared with no pantoprazole to prevent upper gastrointestinal (GI) bleed among invasively ventilated patients.
This is an economic evaluation conducted alongside the
The trial was approved by each participating institution; this economic evaluation was approved by the Hamilton Integrated Research Ethics Board. Given widespread daily use of proton pump inhibitors for critically ill patients, the results of this economic evaluation will be of high relevance to patients, family members, physicians, pharmacists, policymakers and guideline developers. Integrated knowledge translation will involve periodic progress reports to collaborators. End-of-study knowledge translation will include rounds, videoconferences, abstracts and slide-decks for intensive care unit quality councils and healthcare organisations, and open-access publications. Patient and family partners will co-create lay language summaries for traditional and social media to help inform all interest groups.
Practice guidelines recommend addressing patient non-medical drivers of health such as access to nutritious food and transportation as part of whole-person care. Emergent electronic health record (EHR)-based tools can enable non-medical needs care coordination, but adoption commonly faces workflow and infrastructure barriers. Targeted implementation support strategies (eg, training, practice facilitation) can enhance technology adoption in healthcare settings, but no prior research has assessed if implementation strategies can improve how care managers use enabling technologies for non-medical needs care coordination. This study will test whether providing implementation support to primary care health centre care management teams improves the adoption of EHR-based enabling technologies to address patients’ non-medical needs.
This hybrid implementation-effectiveness type 2 pragmatic trial has a mixed methods design. The primary outcomes include: (1) Whether patients enrolled in care management programmes have been screened for unmet non-medical health-related needs and (2) Whether patients with identified unmet non-medical health-related needs received a referral to a community organisation to address their need. The secondary outcomes include: (1) Whether referrals for financial-related non-medical needs had a documented outcome in the EHR, such as successful connection to services, service unavailability or other disposition statuses, (2) Whether the referral outcomes indicated ‘successful connection to services’ and (3) Clinical markers including hypertension and diabetes control. Formative evaluation of barriers and facilitators to using EHR tools to conduct non-medical needs screening, referrals and tracking of receipt of services will include semi-structured interviews and a ‘guided tour’ of enabling technology used by care managers. A modified Delphi process will then inform the development of a set of implementation strategies for inclusion in the intervention. The intervention will be piloted in three health centres, refined, then tested in a stepped-wedge cluster-randomised trial in 20 health centres.
We obtained ethics approval for all study activities from Advarra Institutional Review Board (registration number #00000971). Results will be disseminated to Health Centres and Health Centre network nationally at meetings and we will disseminate to researchers via manuscripts in peer-reviewed journals and scientific meetings.
Cellulitis is a common bacterial skin infection causing significant pain, swelling and impact on daily activities, frequently leading to emergency department presentations and hospital admissions. While antibiotics are the mainstay of treatment, they do not directly address inflammation, often resulting in persisting or worsening symptoms in the initial days. Corticosteroids, with their potent anti-inflammatory effects, have shown benefit in other acute infections but are not currently standard care for patients with cellulitis. This trial aims to determine if adjunctive oral dexamethasone can reduce pain and improve outcomes in adults with cellulitis presenting to UK urgent secondary care settings.
This is a pragmatic, multicentre, double-blind, placebo-controlled, randomised, parallel group, phase 3 superiority trial, with an internal pilot and parallel health economic evaluation. Adult patients (≥16 years) with a clinical diagnosis of cellulitis (at any body site except the orbit) presenting to urgent secondary care will be screened for eligibility. 450 participants will be randomised (1:1) to receive either two 8 mg doses of oral dexamethasone or matched placebo, administered approximately 24 hours apart, in addition to standard antibiotic therapy. The primary outcome is total pain experienced over the first 3 days postrandomisation, calculated using the standardised area under the curve from pain scores (Numerical Rating Scale 0–10) across up to seven timepoints. Secondary outcomes include health-related quality of life (EuroQol 5 Dimension 5 Level), patient global impression of improvement, analgesia and antibiotic usage, hospital (re)admissions, complications, unscheduled healthcare use, cellulitis recurrence and cost-effectiveness at 90 days. The primary estimand will apply a treatment policy approach to intercurrent events.
The trial has received ethical approval from South Central—Oxford B Research Ethics Committee (reference: 24/SC/0289) and will be conducted in compliance with Good Clinical Practice and applicable regulations. Informed consent will be obtained from all participants. A model consent form can be seen in . Findings will be disseminated through peer-reviewed publications and conference presentations, and to patient groups and relevant clinical guideline committees.
Fibrosis is a pathological feature that can occur in a wide range of diseases including diabetes mellitus. We investigated whether in people with type 1 (T1DM) or type 2 diabetes mellitus (T2DM), glycaemia or diabetes-related complications are associated with fibrotic diseases.
Retrospective cohort study using UK Clinical Resource Datalink (CPRD) Aurum and Hospital Episode Statistics.
We included people with prevalent T1DM or T2DM as of 31 December 2015 (recorded in CPRD Aurum), eligible for linkage with Hospital Episode Statistics and followed up for 3 years.
We defined diabetes status using blood/urine biomarkers and complications. In the T2DM cohort, we also investigated exposures of hyperglycaemia, insulin resistance and metformin prescription. Fibrotic condition diagnoses were determined from both primary and secondary care records. Logistic regression analyses were undertaken to understand the strength of association between diabetes status/diabetic complications and fibrotic conditions, respectively.
The T1DM cohort consisted of 9669 people while the T2DM cohort included 504 066 people. In T1DM, we found that albuminuria was associated with lung fibrosis (ORadj: 2.07, 99% CI 1.35 to 2.17), and microvascular complications were associated with atherosclerosis (ORadj: 1.81, 99% CI 1.18 to 2.77) and cardiomyopathy (ORadj 1.53, 99% CI:1.15 to 2.04). In the T2DM cohort, both glycaemia above target and diabetes complications were associated with most fibrotic conditions.
Within the T1DM population, no consistent association between diabetes status and all fibrotic diseases was observed. More research is required to understand whether the association between diabetes complications and fibrotic diseases is due to shared risk factors or whether glycaemia in T2DM may be influenced by fibrotic pathology.
Breast cancer is common and women requiring mastectomy will be offered a breast reconstruction if they are surgically suitable candidate. Breast reconstruction can be performed at the same time as the mastectomy (immediate) or delayed to a second operation after cancer treatments. The reconstruction can either use the patients’ own tissue to make the breast (autologous) or use a prosthesis to make the breast in the form of a fixed or expandable volume implant (implant-based breast reconstruction, IBBR). Immediate breast reconstruction on top of the chest wall muscles (prepectoral) is performed worldwide. This operation involves the use of a synthetic or biological mesh placed around the implant under the skin. Increasingly, surgeons are performing this technique without the use of mesh. Both techniques, with and without mesh, have not been compared in a head-to-head randomised controlled trial (RCT); therefore, surgeons and patients do not have high quality data to guide their decision making in this area.
UK-based pragmatic multicentre randomised controlled feasibility trial. The primary aim is to determine the feasibility of a definitive RCT comparing the clinical and cost-effectiveness of no-mesh versus mesh-assisted prepectoral breast reconstruction. Secondary objectives will explore patient understanding of mesh and willingness to be randomised within an RCT; determine if it is possible to collect data to inform a future economic analysis on the use of mesh in breast reconstruction and determine the feasibility of measuring breast biomechanics pre-surgery and post breast reconstruction surgery. Total number of patients to be included: 40 (20 per arm).
This study will be conducted in compliance with the Declaration of Helsinki. Ethical approval has been obtained. Ethics Ref: 23/SC/0302; IRAS Project ID: 301 423. The results of this study will be published in a peer-reviewed medical journal, independent of the results, following the Consolidated Standards of Reporting Trials standards for RCTs.
Thanks to the introduction of recent national guidelines for treating herpes simplex virus (HSV) encephalitis, health outcomes have improved. This paper evaluates the health system costs and the health-related quality of life implications of these guidelines.
A sub-analysis of data from a prospective, multi-centre, observational cohort ENCEPH-UK study conducted across 29 hospitals in the UK from 2012 to 2015.
Data for patients aged ≥16 years with a confirmed HSV encephalitis diagnosis admitted for treatment with aciclovir were collected at discharge, 3 and 12 months.
Patient health outcomes were measured by the Glasgow outcome score (GOS), modified ranking score (mRS) and the EuroQoL; healthcare costs were estimated per patient at discharge from hospital and at 12 months follow-up. In addition, Quality Adjusted Life Years (QALYs) were calculated from the EQ-5D utility scores. Cost–utility analysis was performed using the NHS and Social Care perspective.
A total of 49 patients were included; 35 were treated within 48 hours, ‘early’ (median (IQR) 8.25 [3.7–20.5]) and 14 were treated after 48 hours ‘delayed’ (median (IQR) 93.9 [66.7–100.1]). At discharge, 30 (86%) in the early treatment group had a good mRS outcome score (0–3) compared with 4 (29%) in the delayed group. According to GOS, 10 (29%) had a good recovery in the early treatment group, but only 1 (7%) in the delayed group. EQ-5D-3L utility value at discharge was significantly higher for early treatment (0.609 vs 0.221, p
This study suggests that early treatment may be associated with better health outcomes and reduced patient healthcare costs, with a potential for savings to the NHS with faster treatment.
Older crime victims may be particularly vulnerable to psychological distress.
To compare the clinical effectiveness of a Victim Improvement Package (VIP) to treatment as usual (TAU) for reducing continued crime-associated distress.
A three-step parallel-group single-blind randomised controlled trial.
Police-reported victims of community crime aged 65 and over were recruited from 12 local authority areas in a major urban city in England, UK.
Selection criteria—inclusion: victims of community crime aged 65 years or more, with significant Generalised Anxiety Disorder (GAD-2) and Patient Health Questionnaire (PHQ-2) distress associated with the crime. Exclusion: type of crime, diagnosis, receipt of cognitive–behavioural therapy (CBT) in the last 6 months; an inability to participate in CBT; cognitive impairment. Participants were typical of our local authority population; 71% were female, 69% white, with the majority of crimes associated with burglary (35%) and theft (26%). 67% (88/131) of the randomised participants were included in the primary analysis.
TAU was compared with TAU plus up to 10 sessions of a cognitively-behaviourally informed VIP, delivered by a mental health charity over 12 weeks.
Timings are in relation to the crime; baseline (3 months), post-VIP intervention (6 months) and follow-up (9 months). The primary outcome was a composite of the Beck Anxiety and Beck Depression Inventories. The primary endpoint was 6 months.
24% (4255/17 611) of reported crime victims were screened, 35% (1505/4255) were distressed. Of 60% (877/1505) rescreened at 3 months, 49% (427/877) remained distressed. Out of our target of 226, 131 participants were randomised; 65 to VIP and 66 to TAU alone. 68% (89/131) completed the primary outcome (post-intervention). The VIP showed no overall benefit; mean VIP –0.41 (SD 0.89) vs mean TAU –0.19 (SD 1.11); standardised mean difference –0.039; 95% CI (–0.39, 0.31), although stratified analyses suggested an effect in burglary victims (n=27, standardised mean difference –0.61; 95% CI (–1.22, –0.002), p=0.049).
Community crime had long-lasting impacts. The police are ideally placed to screen for distress, present in 35% of victims, but only 58% of participants were recruited and the cognitive–behavioural therapy was not delivered competently. Further research on victim care and improving the delivery and quality of therapy is required.
All procedures were approved by the University College London (UCL) Research Ethics Committee on 17 March 2016 (6960/001). International Standard Randomised Controlled Trial Number is ISRCTN16929670:
FreshRSS 