Search results

Echocardiography reporting in heart failure with preserved ejection fraction: Delphi consensus study.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome in which signs and symptoms of heart failure (HF) occur despite a normal left ventricular ejection fraction. Transthoracic echocardiography (TTE) is the first-line imaging modality but disparities in patient pathways across the UK can lead to delayed diagnosis and treatment. We aimed to develop and validate a consistent, clinically appropriate and practical approach for reporting the echocardiographic suspicion of HFpEF. METHODS: Using the Delphi method, a steering group of nine UK experts identified key domains for discussion and generated consensus statements relevant to the echocardiographic detection of HFpEF. Using a four-point Likert scale, a survey including all statements was disseminated among a wider audience of healthcare professionals to determine agreement. A consensus threshold of 75% agreement was defined as 'strong' and ≥90% as 'very strong'. RESULTS: A total of 34 consensus statements were generated in seven domains: (1) challenges in the system approach to HFpEF; (2) enhancing referral for specialist review including echocardiography; (3) confidence in using a summary statement in an echo report; (4) identifying HFpEF and its underlying aetiology; (5) HF awareness, training and education; (6) refining multidisciplinary team roles in decision-making; (7) optimising patient experience.135 UK specialists experienced in managing HF participated in the survey, including physiologists/clinical scientists (n=43), HF specialist nurses (n=35), cardiologists (n=34), general practitioners (n=12), pharmacists (n=4) and others (n=7). 20 of 34 (59%) statements achieved very strong agreement, 10 of 34 (29%) achieved strong agreement and 4 of 34 (12%) did not meet the consensus threshold. CONCLUSIONS: Diagnosis of HFpEF requires access to essential diagnostic tools. Establishing standardised pathways for specialist assessment and referral, including TTE reporting of HFpEF, may help eliminate diagnostic delays and geographical disparities. Further education and awareness are crucial for improving detection rates, prompt referral and patient experience.

Exploring health and social care preferences for people with dementia and mild cognitive impairment: a systematic review of discrete choice experiments

Objectives: Dementia is associated with behaviour change, and impaired ability to remember and think. This review focuses on key findings and methodological processes from discrete choice experiments (DCEs) to inform health and social care interventions for people living with dementia or mild cognitive impairment. Method: Six databases were searched to July 2023 using terms for DCEs, dementia and mild cognitive impairment. Titles, abstracts, and full texts were individually screened by two reviewers. PRISMA reporting guidelines were followed throughout. Study quality was assessed using the Lancsar and Louviere checklist. Results were summarised in a narrative synthesis. The study was PROSPERO registered (CRD42022368182). Results: Nine studies were included. DCE attributes included service provision, setting characteristics, provider characteristics, availability, cost, and clinical outcomes. Studies predominantly included the general population or patient representatives with only two studies incorporating preferences of people living with dementia. Conclusion: Respondents preferred individualised home support, and to avoid relocation. Studies suggested benefit to day centres, and greater flexibility in dementia care provision. Authors noted relative preference could differ according to personal characteristics reinforcing the need for tailored provision. Future DCEs should include respondents with early-stage dementia and other cognitive impairments, taking care to ensure appropriate design for such populations.

Patients' acceptance of a penicillin allergy de-labelling programme in primary care.

BACKGROUND: About 6% of the UK general practice population has a record of a penicillin allergy but fewer than 10% of these people are likely to be truly allergic. Consequently, a significant portion of the population is denied first line antibiotics. The ALABAMA trial aimed to determine if a penicillin allergy assessment pathway (PAAP) was safe and effective in de-labelling patients as allergic and improving antibiotic prescribing and patient health outcomes. AIMS: To investigate patients' experience of penicillin allergy testing (PAT) and their acceptance of de-labelling following a negative allergy test. DESIGN & SETTING: This was a qualitative study using semi-structured interviews with patients who took part in the PAAP intervention arm of the ALABAMA trial. METHOD: As part of a mixed-methods process evaluation embedded in the ALABAMA trial, we conducted interviews with patients in the PAAP intervention arm. Data from interviews with patients was analysed using thematic analysis. RESULTS: Of the 28 participants interviewed, two received a positive PAT result and 26 received a negative PAT result; of these, 24 accepted and two declined de-labelling. At point of trial recruitment, many patients already doubted that they were allergic to penicillin. Patients were happy to attend PAT and felt cared for and safe at the hospital. These factors led to most people trusting their negative test result and accepting de-labelling. CONCLUSION: The patients we interviewed engaged with the PAAP intervention and, when testing negative, were predominantly willing to have their allergy record changed and to take penicillin in future. We highlight factors which influenced patients' acceptance of de-labelling to facilitate future adoption of PAAP. These factors, which we should consider when planning for penicillin allergy testing services, were: patients identifying themselves as low risk before the test, PAT being perceived as trustful and safe, patients previous experience of penicillin allergy and reactions, patients understanding of penicillin reactions and clear communication after de-labelling.

Saline nasal irrigation for acute sinusitis (SNIFS II): a randomised controlled pilot trial with nested process evaluation.

BACKGROUND: Despite having marginal beneficial effects, antibiotics are routinely prescribed in adults with acute sinusitis. Alternative interventions for this common condition are urgently needed. AIM: To assess the feasibility and acceptability of saline nasal irrigation for acute sinusitis. DESIGN & SETTING: Randomised controlled pilot trial with nested process evaluation in 24 English general practices between October 2019 and May 2021. METHOD: Participants were randomised to advice to high volume hypertonic saline nasal irrigation with a delayed antibiotic prescription or usual care. Feasibility outcomes included recruitment and follow-up rates, adherence, and acceptability of the intervention. RESULTS: Of those invited, 81/107 (76%) consented and were randomised (42 intervention, 39 usual care). Two participants were excluded due to ineligibility. Antibiotic prescribing strategies were recorded at baseline for 79/79 (100%), with no or delayed antibiotics prescribed in 60% (24/40) of the saline group versus 38% (15/39) of the usual care group. At follow-up, 80% (63/79) of participants recorded whether they consumed antibiotics or not. Among those from the intervention group who returned a symptom diary, 96% (22/23) and 65% (15/23) reported using saline nasal irrigation during the first and second week, respectively. Semi-structured interviews with 16 participants revealed that most were positive about trial participation and viewed saline nasal irrigation as acceptable, noting it as alternative to antibiotics. CONCLUSION: Saline nasal irrigation is deemed acceptable for adults with acute sinusitis and a trial of such intervention is feasible. A large trial is warranted to assess the effectiveness of this intervention for this common condition.

Implementing in-vitro diagnostic point-of-care tests in community health care: how can we make this work?

A group psychological intervention for postnatal depression in British mothers of South Asian origin - the ROSHNI-2 RCT.

BACKGROUND: Postnatal depression is more common in British South Asian women than white women in the United Kingdom. Despite empirical evidence suggesting the effectiveness of cognitive-behavioural therapy as a first line of treatment, little evidence is available regarding its applicability to different minority ethnic groups. OBJECTIVES: Determining the clinical and cost-effectiveness of a culturally adapted group psychological intervention (Positive Health Programme) in primary care for British South Asian women with postnatal depression compared with treatment as usual. SETTING: General practices and children's centres in the North West, East Midlands, Yorkshire, Glasgow and London. PARTICIPANTS: British South Asian women meeting the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) depression criteria, aged 16 years or above, with infants up to 12 months. DESIGN: A multicentre randomised controlled trial with an internal pilot and partially nested design to compare treatment as usual plus the Positive Health Programme with treatment as usual in British South Asian women with postnatal depression, with a qualitative study to examine the acceptability and feasibility of the intervention. INTERVENTION: The Positive Health Programme, a culturally adapted group intervention based on the principles of cognitive-behavioural therapy delivered by facilitators over 12 sessions. OUTCOMES MEASURES: The primary outcome was recovery from depression (Hamilton Depression Rating Scale ≤ 7) at end of intervention (approximately 4-6 months). Analysis of the primary outcome and the long-term follow-up (at 12 months) used a logistic random-effects model to estimate the odds ratio of caseness between treatments, adjusting for centre, severity of depression and education at baseline. Cost data were collected using an Economic Patient Questionnaire. RESULTS: Seven hundred and thirty-two participants across four study centres were randomised by the Manchester Clinical Trials Unit. At 4 months, almost half of patients in the treatment (Positive Health Programme) group were recovered (138 or 49%), whereas 105 (37%) were recovered in the control (treatment as usual) group. By 12 months, the control (treatment as usual) and treatment (Positive Health Programme) group had over 50% recovery at 140 (54%) and 141 (54%), respectively. For the primary outcome, recovery from postnatal depression at end of intervention, we found a significant effect such that the odds of achieving recovery in the treatment group were almost twice as high compared to the treatment as usual group (odds ratio 1.97, 95% confidence interval 1.26 to 3.10). Between the two groups, there was no significant difference in the odds of recovery at 12 months (odds ratio 1.02, 95% confidence interval 0.62 to 1.66), highlighting a need for more intensive therapies and/or longer-term care plans for this group of patients. QUALITATIVE RESULTS: The intervention was considered feasible and acceptable from the perspectives of Positive Health Programme participants, facilitators, and general practitioners. The findings suggest improved emotional and social support and an enhanced sense of well-being. ECONOMIC EVALUATION: Positive Health Programme implementation was estimated to cost an average of £408 per participant. The intention-to-treat analysis shows that the Positive Health Programme intervention costs £22,198 per quality-adjusted life-year gain. Positive Health Programme was cost-effective on average but with a substantial uncertainty: the probability that Positive Health Programme was cost-effective was 44% (65%) at the willingness to pay £20,000 (£30,000) per quality-adjusted life-year. The Positive Health Programme was highly cost-effective for those who attended 5-8 sessions, costing £9040 per quality-adjusted life-year. LIMITATIONS: The study sample limits generalisability with other ethnic minority groups, and the cost-effectiveness analysis did not explore recall bias. CONCLUSIONS: The results of this study provide robust evidence that the culturally adapted psychological intervention for postnatal depression in South Asian women is effective at the primary end point and acceptable to women. FUTURE WORK: Further development of the Positive Health Programme intervention and evaluation, with longer-term outcome follow-ups and exploration of cost-effectiveness of remote delivery of the Positive Health Programme. STUDY REGISTRATION: Current Controlled Trials ISRCTN10697380. FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/68/08) and is published in full in Health Technology Assessment; Vol. 29, No. 6. See the NIHR Funding and Awards website for further award information.

The World Hip Trauma Evaluation (WHiTE) platform trial: a framework for randomized comparisons of interventions for fragility hip fracture

AimsHip fracture is one of the biggest challenges facing patients and healthcare systems. Worldwide, there are currently 1.3 million hip fractures per year, projected to rise to more than six million by 2050. This protocol describes a platform trial framework, designed to efficiently deliver multiple randomized comparisons of interventions for patients with a fragility hip fracture.MethodsAll patients aged 60 years and over with a hip fracture presenting to the World Hip Trauma Evaluation (WHiTE) recruitment centres will be considered for eligibility for each of the randomized comparisons appended to the platform at the time of recruitment. They will be offered the opportunity to take part in any or all of the randomized comparisons for which they are eligible. Comparisons may be contemporaneous or distributed throughout the treatment pathway. This master protocol describes the trial procedures, core dataset, and documentation. It describes those components of the research process which will be consistent between randomized comparisons. Where additional procedures are planned, specific to a randomized comparison, these will be described in a separate appendix protocol for that randomized comparison.ConclusionThe WHiTE platform trial will provide randomized evidence regarding the clinical and cost-effectiveness of interventions to improve outcomes for patients with fragility hip fracture. Findings will inform national and international policy and practice guidelines for the management of patients with a hip fracture.Cite this article: Bone Jt Open 2025;6(4):383–390.

Public health and general practice working together.

An international comparison of longitudinal health data collected on long COVID in nine high income countries: a qualitative data analysis.

BACKGROUND: Long coronavirus disease (COVID) presents a significant health challenge. Long-term monitoring is critical to support understanding of the condition, service planning and evaluation. We sought to identify and examine longitudinal health data collected on long COVID to inform potential decisions in England regarding the rationale for data collection, the data collected, the sources from which data were collected and the methods used for collection. METHODS: We included datasets in high-income countries that experienced similar coronavirus disease 2019 (COVID-19) waves to England pre-vaccine rollout. Relevant datasets were identified through literature searches, the authors' networks and participants' recommendations. We undertook semi-structured interviews with individuals involved in the development and running of the datasets. We held a focus group discussion with representatives of three long COVID patient organisations to capture the perspective of those with long COVID. Emergent findings were tested in a workshop with country interviewees. RESULTS: We analysed 17 datasets from nine countries (Belgium, Canada, Germany, Italy, the Netherlands, New Zealand, Sweden, Switzerland and the United Kingdom). Datasets sampled different populations, used different data collection tools and measured different outcomes, reflecting different priorities. Most data collection was research (rather than health care system)-funded and time-limited. For datasets linked to specialist services, there was uncertainty surrounding how long these would continue. Definitions of long COVID varied. Patient representatives' favoured self-identification, given challenges in accessing care and receiving a diagnosis; New Zealand's long COVID registry was the only example identified using this approach. Post-exertion malaise, identified by patients as a critical outcome, was absent from all datasets. The lack of patient-reported outcome measures (PROMs) was highlighted as a limitation of datasets reliant on routine health data, although some had developed mechanisms to extend data collection using patient surveys. CONCLUSIONS: Addressing research questions related to the management of long COVID requires diverse data sources that capture different populations with long COVID over the long-term. No country examined has developed a comprehensive long-term data system for long COVID, and, in many settings, data collection is ending leaving a gap. There is no obvious model for England or other countries to follow, assuming there remains sufficient policy interest in establishing a long-term long COVID patient registry.

A viro-immunological model to characterize the antiviral effect of molnupiravir in SARS-CoV-2-infected outpatients: implication for treatment duration.

BACKGROUND: The antiviral efficacy of molnupiravir against SARS-CoV-2 is controversial. Here, we develop a model integrating viral and immune dynamics to characterize the mechanism of action of molnupiravir in vivo and its impact on viral dynamics, during and after treatment. METHODS: We analysed data from the PANORAMIC trial, where 577 outpatients were randomised shortly after symptom onset to receive usual care or molnupiravir for 5 days, and where viral and immunological data were collected for two weeks. We developed a mathematical model that characterized virus/host interaction and accounted for the impact of molnupiravir on viral replication and mutagenesis. The model was used to explore the impact of longer treatment duration. RESULTS: Molnupiravir reduced RNA replication with an efficacy that reached 93% at the end of a five-day treatment. This effect was mediated through two different pathways, one that increased transition mutation frequency, and other that directly inhibited viral production. Accordingly five-day treatment shortened the median time to clearance of both RNA and infectious virus by approximately 2 days. Treatment duration of 10 days could reduce the time to RNA clearance by 5 days and reduce the occurrence of viral rebounds. Longer treatment durations might be needed in case of post-exposure prophylaxis. CONCLUSIONS: Our model suggests that molnupiravir acts primarily on viral replication, and does not act specifically on viral infectivity. Longer administration of molnupiravir may reduce rebound rate and shorten time to viral clearance.

Prevalence, clinical management, and outcomes of adults hospitalised with endemic arbovirus illness in southeast Europe (MERMAIDS-ARBO): a prospective observational study

Background: Arboviruses have expanded into new regions in Europe, yet data indicate gaps in disease notifications and a risk of further spread. We aimed to report on prevalence, clinical management, and outcomes of endemic arbovirus infections in southeast Europe. Methods: In this prospective observational study (MERMAIDS-ARBO), we enrolled adults (age ≥18 years) hospitalised with an arbovirus-compatible disease syndrome within 21 days of symptom onset across 21 hospitals in seven countries in southeast Europe over four arbovirus seasons (May 1–Oct 31, during 2016–19). We obtained data from case report forms completed by site investigators on admission and discharge. Participants were excluded if they had non-infectious CNS disorders, symptoms of another confirmed cause, an identified focal source of infection, or symptoms caused by recurrence of a pre-existing condition. The primary outcome was the proportion of participants with confirmed or probable acute infections with West Nile virus (WNV), tick-borne encephalitis virus (TBEV), Crimean–Congo haemorrhagic fever virus (CCHFV), or Toscana virus (TOSV), per reference laboratory criteria. Secondary outcomes were the proportions of patients treated with antivirals, antibiotics, or corticosteroids; the proportion of patients requiring intensive care; hospital length of stay; and mortality. Findings: Of 2896 adults screened for eligibility, 929 were recruited and 913 met protocol-defined eligibility criteria (median age 43·1 years [IQR 29·5–59·7]; 550 [60%] men, 361 [40%] women, and two [<1%] with missing data). 530 (58%) participants presented with suspected meningitis, encephalitis, or both, and 318 (35%) with fever plus myalgia, fever plus arthralgia, or both. 820 (90%) reported no international travel within 21 days before symptom onset. 727 (80%) were administered antibiotics, 379 (42%) corticosteroids, and 222 (24%) antivirals. The median length of hospital stay was 9 days (IQR 6–14), and 113 (12%) required intensive care. Of 847 participants with a reference laboratory sample who met full eligibility criteria for analysis, 110 (13%) were diagnosed with 114 confirmed or probable acute arbovirus infections (four had coinfections or cross-reactivity): one (<1%) with CCHFV, 16 (2%) with TBEV, 44 (5%) with TOSV, and 53 (6%) with WNV. There was one death (<1%) of an individual with WNV. Of the 110 participants, 49 (45%) had a local clinician-attributed arbovirus discharge diagnosis. Interpretation: Our data highlight the need to strengthen arbovirus surveillance systems for the early detection of emerging and re-emerging outbreaks, including investments to increase awareness of arbovirus infections among clinicians, to improve access to specialist diagnostics, and to develop effective and accessible vaccines and treatments to protect populations and health systems in southeast Europe. Funding: European Commission and Versatile Emerging infectious disease Observatory. Translations: For the Greek, Albanian, Romanian, Bosnian, Serbian, and Croatian translation of the summary see Supplementary Materials section.

Multi-antigen serology and a diagnostic algorithm for the detection of arbovirus infections as novel tools for arbovirus preparedness in southeast Europe (MERMAIDS-ARBO): a prospective observational study

Background: Arboviruses are increasingly affecting Europe, partly due to the effects of climate change. This increase in range and impact emphasises the need to improve preparedness for emerging arboviral infections that often co-circulate and might have overlapping clinical syndromes. We aimed to strengthen surveillance networks for four clinically relevant arboviruses in southeast Europe. Methods: This study reports an in-depth analysis of the MERMAIDS-ARBO prospective observational study in adults (ie, aged ≥18 years) hospitalised with an arbovirus-compatible disease syndrome in 21 hospitals in seven countries in southeast Europe over four arbovirus seasons (May 1–Oct 31, 2016–19) to obtain arbovirus prevalence outcomes. The main objectives of the MERMAIDS-ARBO study, describing the clinical management and outcomes of four arboviruses endemic to southeast Europe, including Crimean–Congo haemorrhagic fever virus (CCHFV), tick-borne encephalitis virus (TBEV), Toscana virus, and West Nile virus (WNV), are reported elsewhere. In this analysis, given the challenges associated with arbovirus diagnostics, we developed a diagnostic algorithm accounting for serology outcomes and sample timing to study arbovirus prevalence in southeast Europe. Serum samples were collected on days 0, 7, 28, and 60 after hospital admission and tested for anti-CCHFV IgG and IgM antibodies with ELISAs (confirmed with an indirect immunofluorescence test) and for IgG and IgM antibodies specific to TBEV, Toscana virus, and WNV with custom-printed protein microarrays (confirmed with virus neutralisation tests). All acute-phase samples were tested by PCR for all four viruses. Descriptive analyses were performed for virus-reactive cases by geography and year, and possible factors (eg, age, sex, and insect bites) associated with virus reactivity were assessed. Findings: Of 2896 individuals screened, 913 were eligible for inclusion, of whom 863 (514 men, 332 women, and 17 unknown) had samples sent to the study reference laboratories and were included in molecular and serological analyses. Some individuals had insufficient clinical data to be included in the clinical analysis, but met the eligibility criteria for and were included here. Serum sampling was incomplete (eg, samples missing from one or more timepoints or no data on time since symptom onset) for 602 (70%) patients, and the timing of collection was often heterogeneous after symptom onset up to 40 days (average median delay of 5–6 days across all timepoints), affecting the ability to diagnose arbovirus infection by serology. By use of an interpretation table incorporating timing and completeness of sampling, one (<1%) participant had a confirmed recent infection with CCHFV, ten (1%) with TBEV, 40 (5%) with Toscana virus, and 52 (6%) with WNV. Most acute confirmed infections of Toscana virus were found in Albania (25 [63%] of 40), whereas WNV was primarily identified in Romania (36 [69%] of 52). Albania also had the highest overall Toscana virus seropositivity (168 [60%] of 282), mainly explained by patients confirmed to be exposed or previously exposed (104 [62%] of 168). Patients without antibodies to WNV or Toscana virus were significantly younger than patients with antibodies (mean difference –8·48 years [95% CI –12·31 to –4·64] for WNV, and –6·97 years [–9·59 to –4·35] for Toscana virus). We found higher odds of Toscana virus reactivity in men (odds ratio 1·56 [95% CI 1·15 to 2·11]; p=0·0055), WNV reactivity with mosquito bites versus no mosquito bites (2·47 [1·54 to 3·97]; p=0·0002), and TBEV reactivity with tick bites versus no tick bites (2·21 [1·19 to 4·11]; p=0·018). Interpretation: This study shows that despite incomplete and heterogeneous data, differential diagnosis of suspected arbovirus infections is possible, and the diagnostic interpretation algorithm we propose could potentially be used to strengthen routine diagnostics in clinical settings in areas at risk for arboviral diseases. Our data highlight potential hotspots for arbovirus surveillance and risk factors associated with these particular arbovirus infections. Funding: European Commission and Versatile Emerging infectious disease Observatory. Translations: For the Greek, Albanian, Romanian, Bosnian, Serbian, and Croatian translation of the summary see Supplementary Materials section.

Better engagement, better evidence: working in partnership with patients, the public, and communities in clinical trials with involvement and good participatory practice

In May 2022, member states of WHO adopted the World Health Assembly WHA75.8 resolution on strengthening clinical trials to provide high-quality evidence on health interventions and to improve research quality and coordination. The resolution recognises the central role of community stakeholders in the clinical trial ecosystem. This paper aims to take stock of the state of the field and define key actions from stakeholders across the clinical trial ecosystem for systematic engagement of patient, public, and community stakeholders in clinical trials. Upfront, sustained, inclusive, and meaningful engagement with patients, public, and community stakeholders intended to benefit from trial outcomes is crucial for several reasons. First, better engagement ensures that trials are well designed and well implemented by considering the unique perspectives and experiences of those they aim to benefit. Second, better engagement enhances the scientific, ethical, and pragmatic value of trials by improving the acceptability, feasibility, and relevance of trial design, implementation, and outcome dissemination. Lastly, improving engagement fosters trust in science and scientists, strengthens research literacy, and contributes to greater trust in research processes. This trust is particularly important in public health emergencies where the urgency for identifying effective interventions, including new vaccines and medicines, often results in limited engagement. In practice, engagement involves activities throughout the trial lifecycle, including research agenda setting, protocol development, trial conduct, and outcome dissemination. Key stakeholders, such as researchers, funders, research ethics committees, and regulators play crucial roles in enabling and implementing engagement via participatory practices. Despite some key markers of progress, challenges remain, including systemic gaps, limited engagement beyond tokenistic involvement, and structural inequities. Addressing these challenges requires action across the clinical trial ecosystem, including strengthening policies, enhancing funding mechanisms, improving regulatory oversight, advocacy, and education of all stakeholders about engagement, and promoting a strong culture of engagement. Advancing the agenda for engagement can promote trust, ethical research conduct, and improve outcomes and wider uptake of findings.

Democratising clinical trials research to strengthen primary health care

The World Health Assembly has called for clinical trials to be strengthened, with broader demographic and geographical inclusion of populations. The objective of this paper is to highlight the importance of rigorous evidence to maximise the health gains of primary health care, and to identify strategies for strengthening clinical trials in primary care. Clinical trials should evaluate interventions of all kinds, including preventive manoeuvres, diagnostics, health service research questions, behavioural and educational interventions, vaccines, therapeutics, and policies. Single question trials can be inefficient and seldom strengthen health systems. New approaches that develop or strengthen health research infrastructure and embed research in primary care will identify effective interventions faster, how to deliver them better, and more accurately determine to whom they should be applied. When patients and community members, together with researchers, contribute to conception, design, and delivery, research will result in more useful, relevant evidence. Traditional site-based recruitment (where the participant comes to the trial) can be complemented by approaches that give people the opportunity to contribute regardless of where they live and receive their health care (taking the trials to the people). However, this cannot be done until regulation is modernised to make it easier for health-care professionals, researchers, and research participants to co-design, deliver, and implement such trials, and to develop processes to coordinate and monitor progress against goals for budget shifts, delivery, engagement, trials activity, and impact. Strengthening primary care trials is especially important in those regions where primary care is most under-resourced and is key to pandemic preparedness. Not doing so risks widening inequities further.

Incidence and characterization of polyglucosan bodies in the cerebella of montserrat orioles (Icterus oberi)

Polyglucosan bodies are accumulations of insoluble glucose polymers and proteins that form intracytoplasmic inclusions in the brain, large numbers of which can be indicative of neurodegenerative diseases such as Lafora disease. Montserrat orioles (Icterus oberi) are an icterid passerine endemic to Montserrat with conservation populations maintained in captivity abroad. We demonstrate that polyglucosan bodies are unusually abundant in the cerebellar molecular and Purkinje cell layers and cerebellar peduncles of captive-bred and wild-caught Montserrat orioles. The bodies are periodic acid-Schiff positive and diastase resistant and label with concanavalin A and for ubiquitin, consistent with those seen in humans. We found no association of the polyglucosan bodies with concurrent neurological lesions or clinical signs, nor with EPM2A and EPM2B gene mutations associated with Lafora disease. We conclude that an abundance of cerebellar polyglucosan bodies may be a normal finding in aged Montserrat orioles and not a threat to the captive breeding population.

The sepsis journey and where digital alerts can help: a qualitative, interview study with survivors and family members in England

IntroductionThe fight against sepsis is an ongoing healthcare challenge, where digital tools are increasingly used with some promising results. The experience of survivors and their family members can help optimize digital alerts for sepsis/deterioration. This study pairs the experiences of survivors of their sepsis journey and family members with their knowledge and views on the role of digital alerts.MethodsA qualitative study with online, semi-structured interviews and focus groups with sepsis survivors and family members in England. Data were analyzed inductively using thematic analysis.ResultsWe included 11 survivors, and 5 family members recruited via sepsis charities and other social media, for a total of 15 sepsis cases. Identified categories correspond to the three stages of the sepsis journey: 1. Pre-hospital, onset symptoms and help-seeking; 2. Hospital admission and stay; 3. Post-sepsis syndrome. The role of digital alerts at each stage of the sepsis journey is discussed. Participants’ experiences were varied, previous sepsis awareness scant, and knowledge of digital alerts minimal. However, participants were confident in the potential of alerts contributing along the sepsis journey. They perceived digital alerts as important in healthcare professionals’ decision-making to expedite identification and treatment of sepsis and suggested their expansion across healthcare services. Participants expressed that awareness should be increased among the general public about digital alerts for sepsis/deterioration.DiscussionIn light of sepsis’ insidious and variable manifestation, the involvement of patients and family members in the development of digital alerts is crucial to optimize their design and deployment towards improving outcomes. Digital alerts should enhance the connection across healthcare services as well as the care quality. They should also enhance the communication between patients and healthcare professionals.Clinical trial registrationThe ClinicalTrials.gov registration identifier for this study is NCT05741801; the protocol ID is 16347.

Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo.

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events.

Ethnicity and Involuntary Hospitalisation: A Study of Intersectional Effects

Implementing the NIHR Oxford Health BRC's Equality, Diversity and Inclusion Strategy

The National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre (BRC) published its first equality, diversity and inclusion (EDI) strategy in 2023. This 5-year strategy aims to establish and enhance the evidence base for EDI, including data collection processes to enhance the diversity of research participants and the workforce. The NIHR has started to collect protected characteristics from applicants for research funding. Although the collection of the data is optional, it could become mandatory in the future. At the Public Mental Health Implementation Centre (PMHIC), of the Royal College of Psychiatry, we undertook a mapping and scoping project to provide Oxford Health BRC partners with insights into data collection for EDI purposes at the local level and identify any challenges and opportunities. This report also proposes solutions to overcoming possible ethical dilemmas, as well as enablers and barriers to implementing the BRC’s EDI strategy.