Background There is considerable interest in technology-enabled remote monitoring in the UK. The aim is to respond to system pressures and improve access, experience and quality of care. There is an urgent need for process, outcome and impact evaluations of interventions at various stages of development and implementation to address evidence gaps around adoption, spread, sustainability and inequalities. Aim DECIDE (Digitally Enabled Care in Diverse Environments) is a centre for rapid evaluation of technology-enabled remote monitoring funded by the National Institute for Health and Care Research (2023 to 2026). It aims to support service users, service commissioners and providers of remote monitoring services, to enable high quality care. Example questions include: Is the technology-enabled remote monitoring innovation needed and, if so, for whom? How are technology-enabled care pathways implemented, and what are associated outcomes and impacts? What are the opportunities and challenges for sustainability, scale-up and spread? Methods A range of qualitative, quantitative and economic methods will be used. Exact methods and questions will be dependent on the focus, scope and scale of each evaluation. Evaluations will be informed by relevant theory, including the Non-Adoption, Abandonment and the challenges to Spread, Scale-up and Sustainability of technological innovation in health and care (NASSS) framework. A User Advisory Group and External Steering Committee, both with diverse voices, will help shape evaluation design, implementation and dissemination. Project-led dissemination will ensure timely sharing of insights and support impact. Conclusion Evaluations will advance understanding of when and for whom technology-enabled remote monitoring innovation is needed; how it works and how factors related to the intervention, implementation process and wider context influence adoption; associated outcomes and impacts, whether and how these tackle inequalities; and potential challenges to scale and spread. We aim to inform decision-making by policymakers, commissioners, providers, patients/service users and researchers.
\n \n\n \n \nBackground: Evidence for the effect of favipiravir treatment of acute COVID-19 on recovery, hospital admissions and longer-term outcomes in community settings is limited. Methods: In this multicentre. open-label, multi-arm, adaptive platform randomised controlled trial participants aged \u226518 years in the community with a positive test for SARS-CoV-2 and symptoms lasting \u226414 days were randomised to: usual care; usual care plus favipiravir tablets (loading dose of 3600 mg in divided doses on day one, then 800 mg twice a day for four days); or, usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery and hospitalisation/death related to COVID-19, within 28 days, analysed using Bayesian models. Recovery at six months was the primary longer-term outcome. Trial registration: ISRCTN86534580. Findings: The primary analysis model included 8811 SARS-CoV-2 positive mostly COVID vaccinated participants, randomised to favipiravir (n = 1829), usual care (n = 3256), and other treatments (n = 3726). Time to self-reported recovery was shorter in the favipiravir group than usual care (estimated hazard ratio 1\u00b723 [95% credible interval 1\u00b714 to 1\u00b733]), a reduction of 2\u00b798 days [1\u00b799 to 3\u00b794] from 16 days in median time to self-reported recovery for favipiravir versus usual care alone. COVID-19 related hospitalisations/deaths were similar (estimated odds ratio 0\u00b799 [0\u00b761 to 1\u00b761]; estimated difference 0% [\u22120\u00b79% to 0\u00b76%]). 14 serious adverse events occurred in the favipiravir group and 4 in usual care. By six months, the proportion feeling fully recovered was 74\u00b79% for favipiravir versus 71\u00b73% for usual care (RR = 1\u00b705, [1\u00b702 to 1\u00b708]). Interpretation: In this open-label trial in a largely vaccinated population with COVID-19 in the community, favipiravir did not reduce hospital admissions, but shortened time to recovery and had a marginal positive impact on long term outcomes.
\n \n\n \n \nVarious open science practices have been proposed to improve the reproducibility and replicability of scientific research, but not for all practices, there may be evidence they are indeed effective. Therefore, we conducted a scoping review of the literature on interventions to improve reproducibility. We systematically searched Medline, Embase, Web of Science, PsycINFO, Scopus and Eric, on 18 August 2023. Any study empirically evaluating the effectiveness of interventions aimed at improving the reproducibility or replicability of scientific methods and findings was included. We summarized the retrieved evidence narratively and in evidence gap maps. Of the 105 distinct studies we included, 15 directly measured the effect of an intervention on reproducibility or replicability, while the remainder addressed a proxy outcome that might be expected to increase reproducibility or replicability, such as data sharing, methods transparency or pre-registration. Thirty studies were non-comparative and 27 were comparative but cross-sectional observational designs, precluding any causal inference. Despite studies investigating a range of interventions and addressing various outcomes, our findings indicate that in general the evidence base for which various interventions to improve reproducibility of research remains remarkably limited in many respects.
\n \n\n \n \nReport from a workshop organised by the British Society of Genetic Medicine and the Centre for Personalised Medicine
\n \n\n \n \nPolyglucosan 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.
\n \n\n \n \nBACKGROUND: 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.
\n \n\n \n \nObjectivesThis is a protocol for a Cochrane Review (intervention). The objectives are as follows: To conduct a living systematic review to assess the benefits and harms of interventions to help people quit vaping compared to each other or to placebo or no intervention. We will also assess how these interventions affect the use of combustible tobacco, and whether effects vary based on participant characteristics.
\n \n\n \n \nBACKGROUND: This study aimed to evaluate the trends in antimicrobial prescription during the first 1.5 years of COVID-19 pandemic. METHODS: This was an observational, retrospective cohort study using patient-level data from Bangladesh, Brazil, India, Italy, Malawi, Nigeria, South Korea, Switzerland and Turkey from patients with pneumonia and/or acute respiratory distress syndrome and/or sepsis, regardless of COVID-19 positivity, who were admitted to critical care units or COVID-19 specialized wards. The changes of antimicrobial prescription between pre-pandemic and pandemic were estimated using logistic or linear regression. Pandemic effects on month-wise antimicrobial usage were evaluated using interrupted time series analyses (ITSAs). RESULTS: Antimicrobials for which prescriptions significantly increased during the pandemic were as follows: meropenem in Bangladesh (95% CI: 1.94-4.07) with increased prescribed daily dose (PDD) (95% CI: 1.17-1.58) and Turkey (95% CI: 1.09-1.58), moxifloxacin in Bangladesh (95% CI: 4.11-11.87) with increased days of therapy (DOT) (95% CI: 1.14-2.56), piperacillin/tazobactam in Italy (95% CI: 1.07-1.48) with increased DOT (95% CI: 1.01-1.25) and PDD (95% CI: 1.05-1.21) and azithromycin in Bangladesh (95% CI: 3.36-21.77) and Brazil (95% CI: 2.33-8.42). ITSA showed a significant drop in azithromycin usage in India (95% CI: -8.38 to -3.49\u2005g/100 patients) and South Korea (95% CI: -2.83 to -1.89\u2005g/100 patients) after WHO guidelines v1 release and increased meropenem usage (95% CI: 93.40-126.48\u2005g/100 patients) and moxifloxacin (95% CI: 5.40-13.98\u2005g/100 patients) in Bangladesh and sulfamethoxazole/trimethoprim in India (95% CI: 0.92-9.32\u2005g/100 patients) following the Delta variant emergence. CONCLUSIONS: This study reinforces the importance of developing antimicrobial stewardship in the clinical settings during inter-pandemic periods.
\n \n\n \n \nBACKGROUND: Effective healthcare leadership has been linked to improved individual and organisational outcomes globally. However, evaluations of healthcare leadership development programmes have often been of low quality. This study investigates the evaluation and decision-making needs of stakeholders for the Oxford Emerging Leaders Programme and aims to redesign its evaluation approach. METHODS: Drawing from Michael Quinn Patton's utilisation-focused evaluation approach, semistructured interviews were conducted with 12 key programme stakeholders. Interviews were thematically analysed to identify key areas for useful and impactful evaluation. RESULTS: Three main themes were identified: impact on patients, impact on healthcare organisations and individual outcomes. Individual outcomes were further divided into skills and qualities. Stakeholders emphasised the importance of measuring improvements in organisational culture, as well as from the perspectives of patients and individual leaders. The need for a multifaceted and longitudinal evaluation approach was highlighted. CONCLUSIONS: The study underscores the importance of aligning evaluation methods with stakeholder needs. Tailoring evaluations to specific programme aims and incorporating both qualitative and quantitative measures can enhance their utility. These insights contribute to the broader literature on healthcare leadership development and programme evaluation.
\n \n\n \n \nRationale: People who work in long-term care institutions (LTCIs), such as doctors, nurses, other health professionals, cleaners and porters (and also family visitors), may have substantial rates of influenza during influenza seasons. They often continue to work when infected with influenza, increasing the likelihood of transmitting influenza to those in their care. The immune systems of care home residents may be weaker than those of the general population; vaccinating care home workers could reduce transmission of influenza within LTCIs. Objectives: To assess the effects of vaccinating healthcare workers in long-term care institutions against influenza on influenza-related outcomes in residents aged 60 years or older. Search methods: We searched the Cochrane Central Register of Controlled Trials (via Cochrane Library), MEDLINE (via Ovid), Embase (via Elsevier), Web of Science (Science Citation Index-Expanded and Conference Proceedings Citation Index - Science), and two clinical trials registries up to 22 August 2024. Eligibility criteria: In this version of the review we restricted eligibility to randomised controlled trials (RCTs) of influenza vaccination of healthcare workers (HCWs) caring for residents aged 60 years or older in LTCIs. Previously we included cohort or case-control studies. Outcomes: Outcomes of interest were: influenza (confirmed by laboratory tests) and its complications (lower respiratory tract infection; hospitalisation or death due to lower respiratory tract infection), all-cause mortality, and adverse events. Risk of bias: We used version one of the Cochrane risk of bias tool for RCTs. Synthesis methods: Two review authors independently extracted data and assessed the risk of bias. We used risk ratios (RRs) with 95% confidence intervals (CIs) to summarise the effects of vaccination on our outcomes of interest. We accounted for clustering by dividing events and sample sizes for each study by an assumed design effect as part of a sensitivity analysis. We used GRADE to assess the certainty of evidence for our outcomes of interest. Included studies: We did not identify any new trials for inclusion in this update. Four cluster-RCTs from Europe (8468 residents) of interventions to offer influenza vaccination for HCWs caring for residents \u2265 60 years in LTCIs provided outcome data that addressed the objectives of our review. The average age of the residents was between 77 and 86 years, and most were female (70% to 77%). The studies were comparable in their intervention and outcome measures. The studies did not report adverse events. The principal sources of bias in the studies related to attrition, lack of blinding, contamination in the control groups, and low rates of vaccination coverage in the intervention arms, leading us to downgrade the certainty of evidence for all outcomes due to serious risk of bias. Synthesis of results: Offering influenza vaccination to HCWs based in LTCIs may have little or no effect on the number of residents who develop influenza compared with those living in care homes where no vaccination is offered (from 5% to 4%) (RR 0.87, 95% CI 0.46 to 1.63; 2 studies, 752 participants; low-certainty evidence). We rated the evidence to be low from one study of 1059 residents showing a slight reduction in lower respiratory tract infection from HCW vaccination (6% versus 4%) (RR 0.70, 95% CI 0.41 to 1.2). The confidence interval is compatible with both a meaningful reduction and a slight increase in infections when illustrated as an absolute effect; 2% to 7%. Taking account of clustering for this outcome increased the confidence interval further, and we rated the evidence as very low-certainty accordingly (RR 0.72, 95% CI 0.28 to 1.85). HCW vaccination programmes may have little or no effect on the number of residents admitted to hospital for respiratory illness (RR 1.02, 95% CI 0.82 to 1.27; 1 study, 3400 participants; low-certainty evidence). There is insufficient evidence to determine whether HCW vaccination impacts on death due to lower respiratory tract infections in residents: 2% of residents in both groups died from lower respiratory tract infections based on the RR of 0.82 (95% CI 0.45 to 1.49; 2 studies, 4459 participants; very low-certainty evidence). HCW vaccination probably leads to a reduction in all-cause deaths from 9% to 6% (RR 0.69, 95% CI 0.60 to 0.80; 4 studies, 8468 participants; moderate-certainty evidence). Authors' conclusions: The effects of HCW vaccination on influenza-specific outcomes in older residents of LTCIs are uncertain. The reduction in all-cause mortality in people observed could not be explained by changes in influenza-specific outcomes. This review did not find information on co-interventions with HCW vaccination: hand washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding admissions, antivirals and asking HCWs with influenza or influenza-like illness not to go to work. Better studies are needed to give greater certainty in the evidence for vaccinating HCWs to prevent influenza in residents aged 60 years or older in LTCIs. Additional studies are needed to further test these interventions in combination. Registration: Protocol (2005): 10.1002/14651858.CD005187.pub. Original review (2006): 10.1002/14651858.CD005187.pub2. Update (2010): 10.1002/14651858.CD005187.pub3. Update (2013): 10.1002/14651858.CD005187.pub4. Update (2016): 10.1002/14651858.CD005187.pub5.
\n \n\n \n \nBackground: It is unclear whether weight loss interventions worsen disordered eating in people living with overweight/obesity. We aimed to systematically evaluate the association between weight loss interventions and disordered eating. Methods: Six databases were searched from inception until September 2024. Trials of weight loss interventions in people with overweight/obesity were included if they reported a validated score for disordered eating on either the Eating Disorder Examination Interview or the Eating Disorder Examination Questionnaire pre- and post-intervention. Interventions included behavioural weight loss programmes (BWL) and pharmacotherapy licenced for weight loss, with or without concurrent psychological support, provided for at least 4 weeks. Pooled standardised mean differences (SMD) in scores of disordered eating were calculated using random effects meta-analyses. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool and the Newcastle\u2013Ottawa scale for randomised and single-arm trials, respectively (PROSPERO ID: CRD42023404792). Findings: Thirty-eight studies with 66 eligible arms (61 interventions: 29 BWL, 11 BWL + pharmacotherapy, 20 BWL + psychological intervention, 1 pharmacotherapy + psychological intervention) and 3364 participants in total were included. The mean weight change was \u22124.7 kg (95% CI: \u22125.7, \u22123.7). Compared with baseline, disordered eating scores improved by \u22121.47 SMD units (95% CI: \u22121.67, \u22121.27, p < 0.001, I2 = 94%) at intervention completion (median of 4 months). Seven randomised trials that directly compared a weight loss intervention to no/minimal intervention reported an improvement of \u22120.49 SMD units (95% CI, \u22120.93, \u22120.04, p = 0.0035, I2 = 73%). Sub-group analyses showed: (a) disordered eating scores improved more in people with an eating disorder at baseline compared with people without high scores, (b) no clear evidence that the association depended upon intervention type, and (c) disordered eating scores improved more in trials rated at low overall RoB. Interpretation: Despite heterogeneity in effect size, weight loss interventions consistently improved disordered eating scores. These findings provide reassurance that weight loss interventions might not worsen disordered eating and may improve it. Funding: Novo Nordisk UK Research Foundation Doctoral Fellowship in Clinical Diabetes.
\n \n\n \n \nBackground Monitoring is the mainstay of chronic kidney disease management in primary care; however, there is little evidence about the best way to do this. Aim To compare the effectiveness of estimated glomerular filtration rate (eGFR) derived from serum creatinine and serum cystatin C to predict renal function decline among those with a recent eGFR of 30-89 ml/min/1.73 m2. Design and setting Observational cohort study in UK primary care. Method Serum creatinine and serum cystatin C were both measured at seven study visits over 2 years in 750 patients aged \u226518 years with an eGFR of 30-89 ml/min/1.73 m2 within the previous year. The primary outcome was change in eGFR derived from serum creatinine or serum cystatin C between 6 and 24 months. Results Average change in eGFR was 0.51 ml/ min/1.73 m2/year when estimated by serum creatinine and -2.35 ml/min/1.73 m2/year when estimated by serum cystatin C. The c-statistic for predicting renal decline using serum creatininederived eGFR was 0.495 (95% confidence interval [CI] = 0.471 to 0.519). The equivalent c-statistic using serum cystatin C-derived eGFR was 0.497 (95% CI = 0.468 to 0.525). Similar results were obtained when restricting analyses to those aged \u226575 or <75 years, or with eGFR \u226560 ml/ min/1.73 m2. In those with eGFR <60 ml/ min/1.73 m2, serum cystatin C-derived eGFR was more predictive than serum creatinine-derived eGFR for future decline in kidney function. Conclusion In the primary analysis neither eGFR estimated from serum creatinine nor from serum cystatin C predicted future change in kidney function, partly due to small changes during 2 years. In some secondary analyses there was a suggestion that serum cystatin C was a more useful biomarker to estimate eGFR, especially in those with a baseline eGFR <60 ml/min/1.73 m2.
\n \n\n \n \nObjectives: To evaluate design, methods, and reporting of impact studies of cardiovascular clinical prediction rules (CPRs). Study Design and Setting: We conducted a systematic review. Impact studies of cardiovascular CPRs were identified by forward citation and electronic database searches. We categorized the design of impact studies as appropriate for randomized and nonrandomized experiments, excluding uncontrolled before-after study. For impact studies with appropriate study design, we assessed the quality of methods and reporting. We compared the quality of methods and reporting between impact and matched control studies. Results: We found 110 impact studies of cardiovascular CPRs. Of these, 65 (59.1%) used inappropriate designs. Of 45 impact studies with appropriate design, 31 (68.9%) had substantial risk of bias. Mean number of reporting domains that impact studies with appropriate study design adhered to was 10.2 of 21 domains (95% confidence interval, 9.3 and 11.1). The quality of methods and reporting was not clearly different between impact and matched control studies. Conclusion: We found most impact studies either used inappropriate study design, had substantial risk of bias, or poorly complied with reporting guidelines. This appears to be a common feature of complex interventions. Users of CPRs should critically evaluate evidence showing the effectiveness of CPRs.
\n \n\n \n \nBackground: Studies have shown that self-monitoring of blood pressure (BP) is effective when combined with co-interventions, but its efficacy varies in the presence of some co-morbidities. This study examined whether self-monitoring can reduce clinic BP in patients with hypertension-related co-morbidity. Methods: A systematic review was conducted of articles published in Medline, Embase, and the Cochrane Library up to January 2018. Randomized controlled trials of self-monitoring of BP were selected and individual patient data (IPD) were requested. Contributing studies were prospectively categorized by whether they examined a low/high-intensity co-intervention. Change in BP and likelihood of uncontrolled BP at 12 months were examined according to number and type of hypertension-related co-morbidity in a one-stage IPD meta-analysis. Results: A total of 22 trials were eligible, 16 of which were able to provide IPD for the primary outcome, including 6,522 (89%) participants with follow-up data. Self-monitoring was associated with reduced clinic systolic BP compared to usual care at 12-month follow-up, regardless of the number of hypertension-related co-morbidities (-3.12 mm Hg, [95% confidence intervals -4.78, -1.46 mm Hg]; P value for interaction with number of morbidities = 0.260). Intense interventions were more effective than low-intensity interventions in patients with obesity (P < 0.001 for all outcomes), and possibly stroke (P < 0.004 for BP control outcome only), but this effect was not observed in patients with coronary heart disease, diabetes, or chronic kidney disease. Conclusions: Self-monitoring lowers BP regardless of the number of hypertension-related co-morbidities, but may only be effective in conditions such obesity or stroke when combined with high-intensity co-interventions.
\n \n\n \n \nThe aim of this study is to systematically examine the proportion of accurate readings attained by automatic digital blood pressure (BP) devices in published validation studies. We included studies of automatic digital BP devices using recognized protocols. We summarized the data as mean and s.d. of differences between measured and observed BP, and proportion of measurements within 5 mm Hg. We included 79 articles (10 783 participants) reporting 113 studies from 22 different countries. Overall, 25/31 (81%), 37/41 (90%) and 34/35 (97%) devices passed the relevant protocols BHS, AAMI and ESH international protocol (ESH-IP), respectively. For devices that passed the BHS protocol, the proportion of measured values within 5 mm Hg of the observed value ranged from 60 to 86% (AAMI protocol 47-94% and ESH-IP 54-89%). The results for the same device varied significantly when a different protocol was used (Omron HEM-907 80% of readings were within 5 mm Hg using the AAMI protocol compared with 62% with the ESH-IP). Even devices with a mean difference of zero show high variation: a device with 74% of BP measurements within 5 mm Hg would require six further BP measurements to reduce variation to 95% of readings within 5 mm Hg. Current protocols for validating BP monitors give no guarantee of accuracy in clinical practice. Devices may pass even the most rigorous protocol with as few as 60% of readings within 5 mm Hg of the observed value. Multiple readings are essential to provide clinicians and patients with accurate information on which to base diagnostic and treatment decisions. \u00a9 2010 Macmillan Publishers Limited All rights reserved.
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