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AnteayerBMJ Open

Comparative effectiveness of educational interventions in neurological disease for healthcare workers and students: a systematic review

Por: Veremu · M. · Jiang · Z. · Gillespie · C. S. · Roman · E. · Cook · W. H. · Chauhan · R. V. · Rafati Fard · A. · Toumbas · G. · Baig · S. · Zipser · C. · Stacpoole · S. · Tetreault · L. · Deakin · N. · Bateman · A. · Davies · B. M.
Objectives

To assess the comparative effectiveness of educational interventions in neurological disease for healthcare workers and students.

Design

Systematic review.

Data sources

Medline, Embase and Cochrane through to 1 June 2025.

Eligibility criteria

Studies evaluating neurological disease educational interventions with a comparator group (observational cohort/randomised controlled trial (RCT)) were included.

Data extraction and synthesis

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

Results

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).

Conclusions

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.

Frailty and the risk of ICU-acquired infections in a randomised trial: a protocol and statistical analysis plan

Por: Fernando · S. M. · Muscedere · J. · Rochwerg · B. · Johnstone · J. · Daneman · N. · Marshall · J. C. · Lauzier · F. · Rudkowski · J. C. · Arabi · Y. M. · Heels-Ansdell · D. · Sligl · W. · Kristof · A. S. · Duan · E. · Dionne · J. C. · St-Arnaud · C. · Reynolds · S. · Khwaja · K. · Cook
Introduction

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.

Methods and analysis

This is a preplanned secondary analysis of the PROSPECT trial (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) which enrolled patients across 44 ICUs in three countries. We will use Cox proportional hazards regression analysis to assess the association of frailty with the clinical outcomes of interest, adjusting for other baseline variables. Baseline demographic and descriptive outcome data will be reported using descriptive statistics. Regression results will be presented as adjusted HRs or ORs with 95% CIs for the associations of each independent variable with the primary, secondary and tertiary outcomes.

Ethics and dissemination

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.

Trial registration number

NCT02462590.

Protocol for an economic evaluation alongside the Re-Evaluating the Inhibition of Stress Erosions (E-REVISE) trial

Por: Humphries · B. · Zytaruk · N. · Heels-Ansdell · D. · Lau · V. · Rochwerg · B. · Fowler · R. · Yao · Y. · Cook · D. J. · Xie · F.
Introduction

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.

Methods and analysis

This is an economic evaluation conducted alongside the Re-Evaluating the Inhibition of Stress Erosions (REVISE) trial (ClinicalTrials.gov NCT03374800). The primary outcome is the incremental cost per clinically important upper GI bleed prevented. The base-case analysis will focus on the entire international cohort of 4821 REVISE patients. The analysis will be conducted from a healthcare payer perspective over a time horizon of ICU admission to hospital discharge or death. To facilitate comparisons across countries given the international scope of the REVISE trial, costs will be presented in United States dollars. The study protocol was developed following the Professional Society for Health Economics and Outcomes Research guidelines.

Ethics and dissemination

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.

Implementation strategies to improve adoption of screening and linkages for non-medical drivers of health in care management using enabling technologies: study protocol for a cluster randomised trial

Por: Cook · N. · Gunn · R. · McGrath · B. M. · Donovan · J. · Pisciotta · M. · Owens-Jasey · C. · Fein · H. L. · Templeton · A. · Larson · Z. · Gold · R.
Introduction

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.

Methods and analysis

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.

Ethics and dissemination

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.

Trial registration number

NCT06489002.

The DEXACELL trial--a protocol for a pragmatic, multicentre, double-blind, placebo-controlled, randomised, parallel group, phase 3 superiority trial to assess the effectiveness and cost-effectiveness of DEXAmethasone as an adjunctive therapy for the manag

Por: Joyce · K. · Lear · R. · Hamilton · F. W. · Arnold · D. · Chaudhuri · E. · Connors · J. · Cook · H. · Creanor · S. · Dawe · P. · Goodwin · E. · Hawton · A. · Hayward · C. · Lasserson · D. S. · Ridd · M. J. · Rowe · D. · Shipley · D. · Taylor · H. · Wainman · H. E. · Williams · O. M. · Carlto
Introduction

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.

Methods and analysis

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.

Ethics and dissemination

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.

Trial registration number

ISRCTN76873478.

Association between hyperglycaemia, diabetes complications and development of fibrotic conditions among people living with type 1 and type 2 diabetes in England: a retrospective cohort study using UK Clinical Resource Datalink Aurum and Hospital Episode S

Por: Massen · G. M. · Cook · S. · Moss · S. T. · Chambers · R. · Jenkins · G. · Allen · R. J. · Wain · L. V. · Stewart · I. · Oliver · N. · Morganstein · D. L. · Quint · J. K. · on behalf of the DEMISTIFI Consortium
Objective

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.

Design and setting

Retrospective cohort study using UK Clinical Resource Datalink (CPRD) Aurum and Hospital Episode Statistics.

Participants

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.

Outcome measures

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.

Results

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.

Conclusions

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.

Prepectoral no mesh versus mesh immediate implant-based reconstruction after mastectomy (Restore-B): a multicentre single-blinded randomised controlled feasibility study protocol

Por: Rolph · R. · Ziebland · S. · Cook · J. A. · Iglesias · C. · Wakefield-Scurr · J. · Malyon · C. · Scaife · J. · Taylor · A. · Hennessy · A. · Markham · S. · Bernstein · M. · Douek · M. · Restore-B Feasibility Collaborative Group · Roy · Rusby · Bonomi · St-John · Agrawal · Smith · Beta
Introduction

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.

Methods and analysis

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).

Ethics and dissemination

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.

Trial registration numbers

NCT06112977; ISRCTN17470747.

Health economic impact of early versus delayed treatment of herpes simplex virus encephalitis in the UK

Por: Defres · S. · Navvuga · P. · Moore · S. · Hardwick · H. · Easton · A. · Michael · B. D. · Kneen · R. · Griffiths · M. · ENCEPHUK Study Group · Medina-Lara · A. · Solomon · T. · Barlow · Beeching · Blanchard · Body · Boyd · Cebria-Prejan · Chadwick · Cooke · Crawford · Davies · Davies
Objective

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.

Design and setting

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.

Study participants

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.

Primary and secondary outcome measures

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.

Results

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

Conclusions

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.

The VIP trial: a randomised controlled trial of the clinical effectiveness of a Victim Improvement Package (VIP) for the reduction of continued symptoms of depression or anxiety in older victims of community crime in an English city

Por: Serfaty · M. · Satchell · J. · Lee · T. · Laycock · G. · Brewin · C. · Buszewicz · M. · Leavey · G. · Drennan · V. M. · Vickerstaff · V. · Cooke · J. · Kessel · A.
Background

Older crime victims may be particularly vulnerable to psychological distress.

Objectives

To compare the clinical effectiveness of a Victim Improvement Package (VIP) to treatment as usual (TAU) for reducing continued crime-associated distress.

Design

A three-step parallel-group single-blind randomised controlled trial.

Setting

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.

Participants

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.

Interventions

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.

Primary and secondary outcome measures

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.

Results

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).

Conclusions

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.

Trial registration number

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: https://doi.org/10.1186/ISRCTN16929670.

Home-based self-administered transcranial direct current stimulation for women affected by primary dysmenorrhoea in Northeastern Brazil: a protocol study

Por: Silva · T. C. d. L. A. d. · Rodrigues · Y. T. · Silva-Filho · E. · Alves de Oliveira · P. C. · Araujo · T. A. B. D. · Bernatavicius · E. · Cook · A. A. · Radyte · E. · Pegado · R. · Micussi · M. T.
Background

The prevalence of women with primary dysmenorrhoea is high and negatively impacts physical and mental health. The intense cyclic episodes of pain generate central nervous system dysfunctional processing. In this sense, strategies focused on the central nervous system are important to re-establish normal functioning. Home-based self-administered transcranial direct current stimulation (tDCS) emerges as a strategy to modulate dysfunctional brain areas and improve the symptoms. This protocol aims to evaluate the effects of home-based self-administered tDCS for pain, premenstrual symptoms, physical performance, quality of life, electroencephalography and patient global impression in women affected by primary dysmenorrhoea.

Methods and analysis

This is a single-centre, parallel, randomised, double-blinded clinical trial protocol. 40 women affected by primary dysmenorrhoea will be randomised into two groups (active-tDCS or sham-tDCS). Then, 20 consecutive sessions of home-based self-administered tDCS will be performed. The assessments will occur at five time points: baseline, after the 20th sessions, at the first, second and third cycles after tDCS interventions (follow-ups). Primary outcome will be pain according to visual analogue scale. Quality of life, premenstrual symptoms screening, depression, anxiety, physical performance, electroencephalography and participants’ satisfaction will be the secondary outcomes. A mixed analysis of variance will calculate the effect of stimulation.

Ethics and dissemination

The study was approved by the ethics committee of the Federal University of Rio Grande do Norte (No. 6.037.756) and registered in the Brazilian Clinical Trials Registry (n° RBR-747k8vb). Participants may withdraw at any time without penalty. Free support will be available from the lead researcher if needed. All procedures will follow Good Clinical Practice and international ethical standards.

Trail registration

https://ensaiosclinicos.gov.br/rg/RBR-747k8vb

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