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Background: The need for effective non-pharmaceutical infection prevention measures such as contact tracing in pandemics remains in care homes, but traditional approaches to contact tracing are not feasible in care homes. The CONTACT intervention introduces Bluetooth-enabled wearable devices (BLE wearables) as a potential solution for automated contact tracing. Using structured reports and reports triggered by positive COVID-19 cases in homes, we fed contact patterns and trends back to homes to support better-informed infection prevention decisions and reduce blanket application of restrictive measures. This paper reports on the evaluation of feasibility and acceptability of the intervention prior to a planned definitive cluster randomised trial of the CONTACT BLE wearable intervention. Methods: CONTACT was a non-randomised mixed-method feasibility study over 2 months in four English care homes. Recruitment was via care home research networks, with individual consent. Data collection methods included routine data from the devices, case report forms, qualitative interviews (with staff and residents), field observation of care, and an adapted version of the NoMaD survey instrument to explore implementation using Normalisation Process Theory. Quantitative data were analysed using descriptive statistical methods. Qualitative data were thematically analysed using a framework approach and Normalisation Process Theory. Intervention and study delivery were evaluated against predefined progression criteria. Results: Of 156 eligible residents, 105 agreed to wear a device, with 102 (97%) starting the intervention. Of 225 eligible staff, 82% (n = 178) participated. Device loss and damage were significant: 11% of resident devices were lost or damaged, ~ 50% were replaced. Staff lost fewer devices, just 6%, but less than 10% were replaced. Fob wearables needed more battery changes than card-type devices (15% vs. 0%). Structured and reactive feedback was variably understood by homes but unlikely to be acted on. Researcher support for interpreting reports was valued. Homes found information useful when it confirmed rather than challenged preconceived contact patterns. Staff privacy concerns were a barrier to adoption. Study procedures added to existing work, making participation burdensome. Study participation benefits did not outweigh perceived burden and were amplified by the pandemic context. CONTACT did not meet its quantitative or qualitative progression criteria. Conclusion: CONTACT found a large-scale definitive trial of BLE wearables for contact tracing and feedback-informed IPC in care homes unfeasible and unacceptable — at least in the context of shifting COVID-19 pandemic demands. Future research should co-design interventions and studies with care homes, focusing on successful intervention implementation as well as technical effectiveness. Trial registration: ISRCTN registration: 11204126 registered 17/02/2021. [ABSTRACT FROM AUTHOR]

Stoichiometric genome-scale metabolic models (generally abbreviated GSM, GSMM, or GEM) have had many applications in exploring phenotypes and guiding metabolic engineering interventions. Nevertheless, these models and predictions thereof can become limited as they do not directly account for protein cost, enzyme kinetics, and cell surface or volume proteome limitations. Lack of such mechanistic detail could lead to overly optimistic predictions and engineered strains. Initial efforts to correct these deficiencies were by the application of precursor tools for GSMs, such as flux balance analysis with molecular crowding. In the past decade, several frameworks have been introduced to incorporate proteome-related limitations using a genome-scale stoichiometric model as the reconstruction basis, which herein are called resource allocation models (RAMs). This review provides a broad overview of representative or commonly used existing RAM frameworks. This review discusses increasingly complex models, beginning with stoichiometric models to precursor to RAM frameworks to existing RAM frameworks. RAM frameworks are broadly divided into two categories: coarse-grained and fine-grained, with different strengths and challenges. Discussion includes pinpointing their utility, data needs, highlighting framework strengths and limitations, and appropriateness to various research endeavors, largely through contrasting their mathematical frameworks. Finally, promising future applications of RAMs are discussed. [ABSTRACT FROM AUTHOR]

Social network analysis can support quality improvement in care homes but traditional approaches to social network analysis are not always feasible in care homes. Recalling contacts and movements in a home is difficult for residents and staff and documentary and other sources of individual contacts can be unreliable. Bluetooth enabled wearable devices are a potential means of generating reliable, trustworthy, social network data in care home communities. In this paper, we explore the empirical, theoretical and real-world potential and difficulties in using Bluetooth enabled wearables with residents and staff in care homes for quality improvement. We demonstrate, for the first time, that a relatively simple system built around the Internet of Things, Bluetooth enabled wearables for residents and staff and passive location devices (the CONTACT intervention) can capture social networks and data in homes, enabling social network analysis, measures, statistics and visualisations. Unexpected variations in social network measures and patterns are surfaced, alongside "uncomfortable" information concerning staff time spent with residents. We show how technology might also help identify those most in need of social contact in a home. The possibilities of technology-enabled social network analysis must be balanced against the implementation-related challenges associated with introducing innovations in complex social systems such as care homes. Behavioural challenges notwithstanding, we argue that armed with social network information, care home staff could better tailor, plan and evaluate the effects of quality improvement with the sub-communities that make up a care home community. [ABSTRACT FROM AUTHOR]

Surface water flooding (SWF) is a severe hazard associated with extreme convective rainfall, whose spatial and temporal sparsity belie the significant impacts it has on populations and infrastructure. Forecasting the intense convective rainfall that causes most SWF on the temporal and spatial scales required for effective flood forecasting remains extremely challenging. National-scale flood forecasts are currently issued for the UK and are well regarded amongst flood responders, but there is a need for complementary enhanced regional information. Here we present a novel SWF-forecasting method, FOREWARNS (Flood fOREcasts for Surface WAter at a RegioNal Scale), that aims to fill this gap in forecast provision. FOREWARNS compares reasonable worst-case rainfall from a neighbourhood-processed, convection-permitting ensemble forecast system against pre-simulated flood scenarios, issuing a categorical forecast of SWF severity. We report findings from a workshop structured around three historical flood events in Northern England, in which forecast users indicated they found the forecasts helpful and would use FOREWARNS to complement national guidance for action planning in advance of anticipated events. We also present results from objective verification of forecasts for 82 recorded flood events in Northern England from 2013–2022, as well as 725 daily forecasts spanning 2019–2022, using a combination of flood records and precipitation proxies. We demonstrate that FOREWARNS offers good skill in forecasting SWF risk, with high spatial hit rates and low temporal false alarm rates, confirming that user confidence is justified and that FOREWARNS would be suitable for meeting the user requirements of an enhanced operational forecast. [ABSTRACT FROM AUTHOR]

Background: Rapid and mass transmission of the SARS-CoV-2 virus amongst vulnerable people led to devastating effects from COVID-19 in care homes. The CONTACT intervention introduced Bluetooth Low Energy 'smart' wearable devices (BLE wearables) as a basis for automated contact tracing in, and feedback on infection risks and patterns to, care homes to try and improve infection prevention and control (IPC). We planned a cluster randomised controlled trial (RCT) of CONTACT. To be feasible, homes had to adopt CONTACT's technology and new ways of working. This paper reports on the process evaluation conducted alongside CONTACT's feasibility study and explains why it lacked the feasibility and acceptability for a definitive RCT. Methods: This mixed method process evaluation used Normalisation Process Theory (NPT) qualitative (interviews, field notes, study case report forms and documents, and observation) and quantitative (survey instruments, counts of activity) data to plan, implement, and analyse the mechanisms, effects, and contextual factors that shaped the feasibility and acceptability of the CONTACT intervention. Results: Thirteen themes within four core NPT constructs explained CONTACT's lack of feasibility. Coherence: the home's varied in the scale and extent of commitment and understanding of the technology and study procedures. Leadership credibility was important but compromised by competing priorities. Management and direct care staff saw CONTACT differently. Work to promote (cognitive participation) and enact (collective action) CONTACT was burdensome and failed to be prioritised over competing COVID-19-related demands on time and scarce human and cognitive resources. Ultimately, staff appraisal of the value of CONTACT-generated information and study procedures (reflexivity) was that any utility for IPC was insufficient to outweigh the perceived burden and complexity involved. Conclusions: Despite implementation failure, dismissing BLE wearables' potential for contact tracing is premature. In non-pandemic conditions, with more time, better co-design and integration of theory-driven implementation strategies tailored to care homes' unique contexts, researchers could enhance normalisation in readiness for future pandemic challenges. Trial registration: ISRCTN registration: 11,204,126 registered 17/02/2021. [ABSTRACT FROM AUTHOR]

Background: The early detection and diagnosis of cancer to reduce avoidable mortality and morbidity is a challenging task in primary health care. There is a growing evidence base on how to enable earlier cancer diagnosis, but well-recognised gaps and delays exist around the translation of new research findings into routine clinical practice. Implementation research aims to accelerate the uptake of evidence by health care systems and professionals. We aimed to identify priorities for implementation research in early cancer diagnosis in primary care. Methods: We used a RAND/UCLA modified Delphi consensus process to identify and rank research priorities. We asked primary care physicians, patients and researchers to complete an online survey suggesting priorities for implementation research in cancer detection and diagnosis. We summarised and presented these suggestions to an 11-member consensus panel comprising nine primary care physicians and two patients. Panellists independently rated the importance of suggestions on a 1–9 scale (9 = very high priority; 1 = very low priority) before and after a structured group discussion. We ranked suggestions using median ratings. Results: We received a total of 115 suggested priorities for implementation research from 32 survey respondents (including 16 primary care professionals, 11 researchers, and 4 patient and public representatives; 88% of respondents were UK-based). After removing duplicates and ineligible suggestions, we presented 37 suggestions grouped within 17 categories to the consensus panel. Following two rounds of rating, 27 suggestions were highly supported (median rating 7–9). The most highly rated suggestions concerned diagnostic support (e.g., access to imaging) interventions (e.g., professional or patient education), organisation of the delivery of care (e.g., communication within and between teams) and understanding variations in care and outcomes. Conclusions: We have identified a set of priorities for implementation research on the early diagnosis of cancer, ranked in importance by primary care physicians and patients. We suggest that researchers and research funders consider these in directing further efforts and resources to improve population outcomes. [ABSTRACT FROM AUTHOR]

Background: People with type 1 diabetes and raised glucose levels are at greater risk of retinopathy, nephropathy, neuropathy, cardiovascular disease, sexual health problems and foot disease. The UK National Institute for Health and Care Excellence (NICE) recommends continuous subcutaneous 'insulin pump' therapy for people with type 1 diabetes whose HbA1c is above 69 mmol/mol. Insulin pump use can improve quality of life, cut cardiovascular risk and increase treatment satisfaction. About 90,000 people in England and Wales meet NICE criteria for insulin pumps but do not use one. Insulin pump use also varies markedly by deprivation, ethnicity, sex and location. Increasing insulin pump use is a key improvement priority. Audit and feedback is a common but variably effective intervention. Limited capabilities of healthcare providers to mount effective responses to feedback from national audits, such as the National Diabetes Audit (NDA), undermines efforts to improve care. We have co-developed a theoretically and empirically informed quality improvement collaborative (QIC) to strengthen local responses to feedback with patients and carers, national audits and healthcare providers. We will evaluate whether the QIC improves the uptake of insulin pumps following NDA feedback. Methods: We will undertake an efficient cluster randomised trial using routine data. The QIC will be delivered alongside the NDA to specialist diabetes teams in England and Wales. Our primary outcome will be the proportion of people with type 1 diabetes and an HbA1c above 69 mmol/mol who start and continue insulin pump use during the 18-month intervention period. Secondary outcomes will assess change in glucose control and duration of pump use. Subgroup analyses will explore impacts upon inequalities by ethnicity, sex, age and deprivation. A theory-informed process evaluation will explore diabetes specialist teams' engagement, implementation, fidelity and tailoring through observations, interviews, surveys and documentary analysis. An economic evaluation will micro-cost the QIC, estimate cost-effectiveness of NDA feedback with QIC and estimate the budget impact of NHS-wide QIC roll out. Discussion: Our study responds to a need for more head-to-head trials of different ways of reinforcing feedback delivery. Our findings will have implications for other large-scale audit and feedback programmes. Trial registration: ISRCTN82176651 Registered 18 October 2022. [ABSTRACT FROM AUTHOR]

Assessment of the genetic similarity between two phenotypes can provide insight into a common genetic aetiology and inform the use of pleiotropy-informed, cross-phenotype analytical methods to identify novel genetic associations. The genetic correlation is a well-known means of quantifying and testing for genetic similarity between traits, but its estimates are subject to comparatively large sampling error. This makes it unsuitable for use in a small-sample context. We discuss the use of a previously published nonparametric test of genetic similarity for application to GWAS summary statistics. We establish that the null distribution of the test statistic is modelled better by an extreme value distribution than a transformation of the standard exponential distribution. We show with simulation studies and real data from GWAS of 18 phenotypes from the UK Biobank that the test is to be preferred for use with small sample sizes, particularly when genetic effects are few and large, outperforming the genetic correlation and another nonparametric statistical test of independence. We find the test suitable for the detection of genetic similarity in the rare disease context. Author summary: The genome-wide association study (GWAS) is a method used to identify genetic variants which contribute to the risk of developing disease. These genetic variants are frequently shared between conditions, such that the study of the genetic basis of one disease can be informed by knowledge of another, similar disease. This approach can be productive where the disease in question is rare such that a GWAS has less power to associate variants with the disease, but there exist larger GWAS of similar diseases. Existing methods do not measure genetic similarity precisely when patients are few. Here we assess a previously published method of testing for genetic similarity between pairs of diseases using GWAS data, the 'GPS' test, against three other methods with the use of real and simulated data. We present a new computational procedure for carrying out the test and show that the GPS test is superior to its comparators in identifying genetic similarity when the sample size is small and when the genetic similarity signal is less strong. Use of the test will enable accurate detection of genetic similarity and the study of rarer conditions using data from better-characterised diseases. [ABSTRACT FROM AUTHOR]

Background: Online studies offer an efficient method of recruiting participants and collecting data. Whilst delivering an online randomised trial, we detected unusual recruitment activity. We describe our approach to detecting and managing suspected fraud and share lessons for researchers. Methods: Our trial investigated the single and combined effects of different ways of presenting clinical audit and feedback. Clinicians and managers who received feedback from one of five United Kingdom national clinical audit programmes were emailed invitations that contained a link to the trial website. After providing consent and selecting their relevant audit, participants were randomised automatically to different feedback versions. Immediately after viewing their assigned feedback, participants completed a questionnaire and could request a financial voucher by entering an email address. Email addresses were not linked to trial data to preserve participant anonymity. We actively monitored participant numbers, questionnaire completions, and voucher claims. Results: Following a rapid increase in trial participation, we identified 268 new voucher claims from three email addresses that we had reason to believe were linked. Further scrutiny revealed duplicate trial completions and voucher requests from 24 email addresses. We immediately suspended the trial, improved security measures, and went on to successfully complete the study. We found a peak in questionnaires completed in less than 20 seconds during a likely contamination period. Given that study and personal data were not linked, we could not directly identify the trial data from the 268 duplicate entries within the 603 randomisations occurring during the same period. We therefore excluded all 603 randomisations from the primary analysis, which was consequently based on 638 randomisations. A sensitivity analysis, including all 961 randomisations over the entire study except for questionnaire completions of less than 20 seconds, found only minor differences from the primary analysis. Conclusion: Online studies offering incentives for participation are at risk of attempted fraud. Systematic monitoring and analysis can help detect such activity. Measures to protect study integrity include linking participant identifiers to study data, balancing study security and ease of participation, and safeguarding the allocation of participant incentives. Trial registration: International Standard Randomised Controlled Trial Number: ISRCTN41584028. Registration date is August 17, 2017. [ABSTRACT FROM AUTHOR]

Background: Seasonal floods pose a commonly-recognised barrier to women's access to maternal services, resulting in increased morbidity and mortality. Despite their importance, previous GIS models of healthcare access have not adequately accounted for floods. This study developed new methodologies for incorporating flood depths, velocities, and extents produced with a flood model into network- and raster-based health access models. The methodologies were applied to the Barotse Floodplain to assess flood impact on women's walking access to maternal services and vehicular emergency referrals for a monthly basis between October 2017 and October 2018. Methods: Information on health facilities were acquired from the Ministry of Health. Population density data on women of reproductive age were obtained from the High Resolution Settlement Layer. Roads were a fusion of OpenStreetMap and data manually delineated from satellite imagery. Monthly information on floodwater depth and velocity were obtained from a flood model for 13-months. Referral driving times between delivery sites and EmOC were calculated with network analysis. Walking times to the nearest maternal services were calculated using a cost-distance algorithm. Results: The changing distribution of floodwaters impacted the ability of women to reach maternal services. At the peak of the dry season (October 2017), 55%, 19%, and 24% of women had walking access within 2-hrs to their nearest delivery site, EmOC location, and maternity waiting shelter (MWS) respectively. By the flood peak, this dropped to 29%, 14%, and 16%. Complete inaccessibility became stark with 65%, 76%, and 74% unable to access any delivery site, EmOC, and MWS respectively. The percentage of women that could be referred by vehicle to EmOC from a delivery site within an hour also declined from 65% in October 2017 to 23% in March 2018. Conclusions: Flooding greatly impacted health access, with impacts varying monthly as the floodwave progressed. Additional validation and application to other regions is still needed, however our first results suggest the use of a hydrodynamic model permits a more detailed representation of floodwater impact and there is great potential for generating predictive models which will be necessary to consider climate change impacts on future health access. [ABSTRACT FROM AUTHOR]

Surface water flooding (SWF) is a severe hazard associated with extreme convective rainfall, whose spatial and temporal sparsity belies the significant impacts it has on populations and infrastructure. Forecasting the intense convective rainfall that causes most SWF on the temporal and spatial scales required for effective flood forecasting remains extremely challenging. National scale flood forecasts are currently issued for the UK and are well regarded amongst flood responders, but there is a need for complimentary enhanced regional information. Here we present a novel SWF forecasting method, FOREWARNS (Flood fOREcasts for Surface WAter at a RegioNal Scale), that aims to fill this gap in forecast provision. FOREWARNS compares reasonable worst-case rainfall from a neighbourhood-processed, convection-permitting ensemble forecast system against pre-simulated flood scenarios, issuing a categorical forecast of SWF severity. We report findings from a workshop structured around three historical flood events in Northern England, in which forecast users indicated they found the forecasts helpful and would use FOREWARNS to complement national guidance for action planning in advance of anticipated events. We also present results from objective verification of forecasts for 82 recorded flood events in Northern England from 2013-2022, and for 725 daily forecasts spanning 2019-2022, using a combination of flood records and precipitation proxies. We demonstrate that FOREWARNS offers good skill in forecasting SWF risk, with high spatial hit rates and low temporal false alarm rates, confirming that user confidence is justified, and that FOREWARNS would be suitable for meeting the user requirements of an enhanced operational forecast. [ABSTRACT FROM AUTHOR]

Natural flood management (NFM) is a method for reducing flooding by using a catchment‐based approach to managing flood risk. Understanding and quantifying the impact of implementing NFM at the catchment scale remains ambiguous with a clear need for robust empirical evidence. A combination of fieldwork, laboratory analysis and modelling was applied to quantify the impacts of land use management changes on catchment flood hazard. Soil hydraulic conductivity was measured under varying land management regimes and used to parameterize a physically based spatially distributed hydrological model (SD‐TOPMODEL). A suite of stakeholder informed land management scenarios was modelled, permitting the quantification of the impact of NFM interventions on the timing and the intensity of the peak discharge at the catchment outlet. The findings support the implementation of NFM interventions as a means of reducing flood hazard within a rural upland catchment. Improved soil infiltration provided the greatest reduction in the intensity and delayed timing of the flood peak for a 10‐year occurrence storm event (7% reduction in peak runoff and 8% increase in lag time) with similar reductions observed for a 100‐year storm event. Catchment wide woodland planting reduced peak flow by 11% during the 100‐year event but was not effective during the 10‐year event. Riparian buffer strips provided consistent reductions in peak flow and in the timing of the peak across both storm events with no significant differences relating to vegetation age. Critically, we observed that the effect of implementing multiple NFM interventions was not additive and that efficiencies can be made in using this modelling approach to prioritize the most effective outcomes. [ABSTRACT FROM AUTHOR]

As the frequency and magnitude of storm events increase with climate change, understanding how season and management influence flood peaks is essential. The influence of season and management of grasslands on flood peak timing and magnitude was modelled for Swindale and Calderdale, two catchments in northern England. Spatially‐Distributed TOPMODEL was used to investigate two scenarios across four storm events using empirically‐based soil and vegetation data. The first scenario applied seasonal changes in vegetative roughness, quantifying the effect on flood peaks at catchment scale. The second scenario modelled the influence of grassland management from historical high‐intensity grazing to a series of natural succession stages between grassland and woodland, and a conservation‐based management. Model outputs were analysed by flow type, measuring total, overland and base flow peaks at the catchment outlet. Seasonal changes to vegetation were found to increase overland flow peaks by up to +2.2% in winter and reduce them by −5.5% in summer compared to the annual average. Percentage changes in flood peak due to hillslope grassland management scenarios were more substantial; overland flow peaks were reduced by up to 41% in Calderdale where extensive woodland development was the most effective mitigation strategy, and up to 35% in Swindale, where a rank grassland dominated catchment was the most effective. Conservation‐based farming practices were also useful, reducing overland flow peak by up to 42% compared to the high intensity grazing scenario. Neither management nor seasonality changed the timing of runoff peaks by >45 min. Where overland flow dominates, especially in catchments with shallow soils, surface roughness was found to be more influential than soil permeability for flood mitigation. We recommend that seasonal changes to roughness are considered alongside the spatial distribution of Natural Flood Management in mosaiced upland catchments. [ABSTRACT FROM AUTHOR]

The resources of small‐scale community‐based flood risk action groups are often limited, hence studies to model and predict the effects of Natural Flood Management are often restrained by time and lack of empirical data to validate results. As a result, representations of hillslope leaky barriers are largely modelled as several equifinal approaches, often without survey data. The geometrical characteristics of hillslope leaky barriers were surveyed for the first time at Hardcastle Crags, Calder Valley. This data informed six 2D hydraulic model representation scenarios with varying combinations of topography modification and roughness increase, allowing the sensitivity of their results to be tested. Results from Scenario 3 (topography modification and roughness increase) estimated total hillslope runoff peak flow to reduce by 16.6% in a 1:1‐year design return period; however, this reduction diminished as rainfall intensity increased. Return periods of over 1:30 year estimated peak flow reductions of <5%. Only 14.3%–21.7% (98–148 m3) of the total additional storage provided by the barriers is mobilised during simulated events. A multi‐peaked rainfall event from December 2015 was also simulated. Although the initial peak flow was reduced by 22.7%, as storage became mobilised, effectiveness reduced significantly for subsequent peaks within the same event. [ABSTRACT FROM AUTHOR]

Background: Audit and feedback aims to improve patient care by comparing healthcare performance against explicit standards. It is used to monitor and improve patient care, including through National Clinical Audit (NCA) programmes in the UK. Variability in effectiveness of audit and feedback is attributed to intervention design; separate randomised trials to address multiple questions about how to optimise effectiveness would be inefficient. We evaluated different feedback modifications to identify leading candidates for further "real-world" evaluation.Methods: Using an online fractional factorial screening experiment, we randomised recipients of feedback from five UK NCAs to different combinations of six feedback modifications applied within an audit report excerpt: use effective comparators, provide multimodal feedback, recommend specific actions, provide optional detail, incorporate the patient voice, and minimise cognitive load. Outcomes, assessed immediately after exposure to the online modifications, included intention to enact audit standards (primary outcome, ranked on a scale of -3 to +3, tailored to the NCA), comprehension, user experience, and engagement.Results: We randomised 1241 participants (clinicians, managers, and audit staff) between April and October 2019. Inappropriate repeated participant completion occurred; we conservatively excluded participant entries during the relevant period, leaving a primary analysis population of 638 (51.4%) participants. None of the six feedback modifications had an independent effect on intention across the five NCAs. We observed both synergistic and antagonistic effects across outcomes when modifications were combined; the specific NCA and whether recipients had a clinical role had dominant influences on outcome, and there was an antagonistic interaction between multimodal feedback and optional detail. Among clinical participants, predicted intention ranged from 1.22 (95% confidence interval 0.72, 1.72) for the least effective combination in which multimodal feedback, optional detail, and reduced cognitive load were applied within the audit report, up to 2.40 (95% CI 1.88, 2.93) for the most effective combination including multimodal feedback, specific actions, patient voice, and reduced cognitive load.Conclusion: Potentially important synergistic and antagonistic effects were identified across combinations of feedback modifications, audit programmes, and recipients, suggesting that feedback designers must explicitly consider how different features of feedback may interact to achieve (or undermine) the desired effects.Trial Registration: International Standard Randomised Controlled Trial Number: ISRCTN41584028. [ABSTRACT FROM AUTHOR]

Background: Implementing evidence-based recommendations is challenging in UK primary care, especially given system pressures and multiple guideline recommendations competing for attention. Implementation packages that can be adapted and hence applied to target multiple guideline recommendations could offer efficiencies for recommendations with common barriers to achievement. We developed and evaluated a package of evidence-based interventions (audit and feedback, educational outreach and reminders) incorporating behaviour change techniques to target common barriers, in two pragmatic trials for four "high impact" indicators: risky prescribing; diabetes control; blood pressure control; and anticoagulation in atrial fibrillation. We observed a significant, cost-effective reduction in risky prescribing but there was insufficient evidence of effect on the other outcomes. We explored the impact of the implementation package on both social processes (Normalisation Process Theory; NPT) and hypothesised determinants of behaviour (Theoretical Domains Framework; TDF).Methods: We conducted a prospective multi-method process evaluation. Observational, administrative and interview data collection and analyses in eight primary care practices were guided by NPT and TDF. Survey data from trial and process evaluation practices explored fidelity.Results: We observed three main patterns of variation in how practices responded to the implementation package. First, in integration and achievement, the package "worked" when it was considered distinctive and feasible. Timely feedback directed at specific behaviours enabled continuous goal setting, action and review, which reinforced motivation and collective action. Second, impacts on team-based determinants were limited, particularly when the complexity of clinical actions impeded progress. Third, there were delivery delays and unintended consequences. Delays in scheduling outreach further reduced ownership and time for improvement. Repeated stagnant or declining feedback that did not reflect effort undermined engagement.Conclusions: Variable integration within practice routines and organisation of care, variable impacts on behavioural determinants, and delays in delivery and unintended consequences help explain the partial success of an adaptable package in primary care. [ABSTRACT FROM AUTHOR]

Background: Audit and feedback entails systematic documentation of clinical performance based on explicit criteria or standards which is then fed back to professionals in a structured manner. There are potential significant returns on investment from partnerships between existing clinical audit programmes in coordinated programmes of research to test ways of improving the effect of their feedback to drive greater improvements in health care delivery and population outcomes. We explored barriers to and enablers of embedding audit and feedback trials within clinical audit programmes. Methods: We purposively recruited participants with varied experience in embedded trials in audit programmes. We conducted qualitative semi-structured interviews, guided by behavioural theory, with researchers, clinical audit programme staff and health care professionals. Recorded interviews were transcribed, and data coded and thematically analysed. Results: We interviewed 31 participants (9 feedback researchers, 14 audit staff and 8 healthcare professionals, many having dual roles). We identified barriers and enablers for all 14 theoretical domains but no relationship between domains and participant role. We identified four optimal conditions for sustainable collaboration from the perspectives of stakeholders: resources, that is, recognition that audit programmes need to create capacity to participate in research, and research must be adapted to fit within each programme's constraints; logistics, namely, that partnerships need to address data sharing and audit quality, while securing research funding to ensure operational success; leadership, that is, enthusiastic and engaged audit programme leaders must motivate their team and engage local stakeholders; and relationships, meaning that trust between researchers and audit programmes must be established over time by identifying shared priorities and meeting each partner's needs. Conclusion: Successfully embedding research within clinical audit programmes is likely to require compromise, logistical expertise, leadership and trusting relationships to overcome perceived risks and fully realise benefits. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified thousands of genetic variants that are associated with complex traits. However, a stringent significance threshold is required to identify robust genetic associations. Leveraging relevant auxiliary covariates has the potential to boost statistical power to exceed the significance threshold. Particularly, abundant pleiotropy and the non-random distribution of SNPs across various functional categories suggests that leveraging GWAS test statistics from related traits and/or functional genomic data may boost GWAS discovery. While type 1 error rate control has become standard in GWAS, control of the false discovery rate can be a more powerful approach. The conditional false discovery rate (cFDR) extends the standard FDR framework by conditioning on auxiliary data to call significant associations, but current implementations are restricted to auxiliary data satisfying specific parametric distributions, typically GWAS p-values for related traits. We relax these distributional assumptions, enabling an extension of the cFDR framework that supports auxiliary covariates from arbitrary continuous distributions ("Flexible cFDR"). Our method can be applied iteratively, thereby supporting multi-dimensional covariate data. Through simulations we show that Flexible cFDR increases sensitivity whilst controlling FDR after one or several iterations. We further demonstrate its practical potential through application to an asthma GWAS, leveraging various functional genomic data to find additional genetic associations for asthma, which we validate in the larger, independent, UK Biobank data resource. Author summary: Genome-wide association studies (GWAS) detect regions of the human genome that are associated with various traits, including complex diseases, but the power to detect these genomic regions is currently limited by sample size. The conditional false discovery rate (cFDR) provides a tool to leverage one GWAS study to improve power in another. The motivation is that if two traits have some genetic correlation, then our interpretation of a low but not significant p-value for the trait of interest will differ depending on whether that SNP shows strong or absent evidence of association with the related trait. Here, we describe an extension to the cFDR framework, called "Flexible cFDR", that controls the FDR and supports auxiliary data from arbitrary distributions, surpassing current implementations of cFDR which are restricted to leveraging GWAS p-values from related traits. In practice, our method can be used to iteratively leverage various types of functional genomic data with GWAS data to increase power for GWAS discovery. We describe the use of Flexible cFDR to supplement data from a GWAS of asthma with auxiliary data from functional genomic experiments. We identify associations novel to the original GWAS and validate these discoveries with reference to a larger, more highly-powered GWAS of asthma. [ABSTRACT FROM AUTHOR]

Background: The rise in opioid prescribing in primary care represents a significant international public health challenge, associated with increased psychosocial problems, hospitalisations, and mortality. We evaluated the effects of a comparative feedback intervention with persuasive messaging and action planning on opioid prescribing in primary care.Methods and Findings: A quasi-experimental controlled interrupted time series analysis used anonymised, aggregated practice data from electronic health records and prescribing data from publicly available sources. The study included 316 intervention and 130 control primary care practices in the Yorkshire and Humber region, UK, serving 2.2 million and 1 million residents, respectively. We observed the number of adult patients prescribed opioid medication by practice between July 2013 and December 2017. We excluded adults with coded cancer or drug dependency. The intervention, the Campaign to Reduce Opioid Prescribing (CROP), entailed bimonthly, comparative, and practice-individualised feedback reports to practices, with persuasive messaging and suggested actions over 1 year. Outcomes comprised the number of adults per 1,000 adults per month prescribed any opioid (main outcome), prescribed strong opioids, prescribed opioids in high-risk groups, prescribed other analgesics, and referred to musculoskeletal services. The number of adults prescribed any opioid rose pre-intervention in both intervention and control practices, by 0.18 (95% CI 0.11, 0.25) and 0.36 (95% CI 0.27, 0.46) per 1,000 adults per month, respectively. During the intervention period, prescribing per 1,000 adults fell in intervention practices (change -0.11; 95% CI -0.30, -0.08) and continued rising in control practices (change 0.54; 95% CI 0.29, 0.78), with a difference of -0.65 per 1,000 patients (95% CI -0.96, -0.34), corresponding to 15,000 fewer patients prescribed opioids. These trends continued post-intervention, although at slower rates. Prescribing of strong opioids, total opioid prescriptions, and prescribing in high-risk patient groups also generally fell. Prescribing of other analgesics fell whilst musculoskeletal referrals did not rise. Effects were attenuated after feedback ceased. Study limitations include being limited to 1 region in the UK, possible coding errors in routine data, being unable to fully account for concurrent interventions, and uncertainties over how general practices actually used the feedback reports and whether reductions in prescribing were always clinically appropriate.Conclusions: Repeated comparative feedback offers a promising and relatively efficient population-level approach to reduce opioid prescribing in primary care, including prescribing of strong opioids and prescribing in high-risk patient groups. Such feedback may also prompt clinicians to reconsider prescribing other medicines associated with chronic pain, without causing a rise in referrals to musculoskeletal clinics. Feedback may need to be sustained for maximum effect. [ABSTRACT FROM AUTHOR]

Background: The rise in opioid prescribing in primary care represents a significant public health challenge, associated with increased psychosocial problems, hospitalisations, and mortality. An evidence-based bimonthly feedback intervention to reduce opioid prescribing was developed and implemented, targeting 316 general practices in West Yorkshire over 1 year.Aim: To understand how general practice staff received and responded to the feedback intervention.Design and Setting: Qualitative process evaluation involving semi-structured interviews, guided by Normalisation Process Theory (NPT), of primary care healthcare professionals targeted by feedback.Method: Participants were purposively recruited according to baseline opioid prescribing levels and degree of change following feedback. Interview data were coded to NPT constructs, and thematically analysed.Results: Interviews were conducted with 21 staff from 20 practices. Reducing opioid prescribing was recognised as a priority. While high achievers had clear structures for quality improvement, feedback encouraged some less structured practices to embed changes. The non-prescriptive nature of the feedback reports allowed practices to develop strategies consistent with their own ways of working and existing resources. Practice concerns were allayed by the credibility of the reports and positive experiences of reducing opioid prescribing. The scale, frequency, and duration of feedback may have ensured a good overall level of practice population reach.Conclusion: The intervention engaged general practice staff in change by targeting an issue of emerging concern, and allowing adaption to different ways of working. Practice efforts to reduce opioid prescribing were reinforced by regular feedback, credible comparative data showing progress, and shared experiences of patient benefit. [ABSTRACT FROM AUTHOR]

Background: Over the last 10 years HENRY has been working to reduce and prevent child obesity by training health and early years professionals to deliver its evidence-based programme to parents. The aim and unique contribution of this study was to evaluate whether training volunteers to deliver this programme on a one-to-one basis was feasible.Methods: Mixed-methods service evaluation with parent-reported pre- and post-programme outcomes and focus groups conducted with parents and volunteer facilitators. The programme consisted of 8 one-to-one sessions delivered weekly by volunteers (n = 18) to build food and activity-related knowledge, skills, and understanding, and improve parenting efficacy, and parent and child eating and physical activity. Programmes took place at parent's (n = 69) home or local community venues in four London boroughs, United Kingdom. Parent-reported parenting efficacy, emotional wellbeing, eating, and physical activity data were captured, alongside parent ratings of the programme and volunteer ratings of the training. Parent and volunteer focus groups explored involvement, expectations, and experiences of the programme, training and delivery, feedback, and impact.Results: Parents were mostly female, had varied ethnic backgrounds, and were often not working but well educated. There were statistically significant improvements of a medium-to-large size in parent and child emotional wellbeing, parenting efficacy, fruit and vegetable consumption, family eating and food purchasing behaviours. Parent ratings of the programme were positive and qualitative data highlighted the holistic nature of the programme, which focused on more than just food, and the relationships with volunteers as key facets. Volunteers were also mostly female, had varied ethnic backgrounds, and were often well educated, but more likely to be employed than parents. Volunteers rated the training and delivery as useful in enabling them to deliver the programme confidently and for their own wellbeing. Despite finding some sessions challenging emotionally, volunteers reported positive family lifestyle improvements by parents and children and that the experience would be useful for future employment.Conclusions: It is feasible to recruit and train volunteers to deliver a structured preschool obesity prevention programme, which parents considered acceptable and enjoyable, with preliminary reports of parent and child benefits. [ABSTRACT FROM AUTHOR]

Novel open reading frames (nORFs) with coding potential may arise from noncoding DNA. Not much is known about their emergence, functional role, fixation in a population or contribution to adaptive radiation. Cichlids fishes exhibit extensive phenotypic diversification and speciation. Encounters with new environments alone are not sufficient to explain this striking diversity of cichlid radiation because other taxa coexistent with the Cichlidae demonstrate lower species richness. Wagner et al. analyzed cichlid diversification in 46 African lakes and reported that both extrinsic environmental factors and intrinsic lineage-specific traits related to sexual selection have strongly influenced the cichlid radiation, which indicates the existence of unknown molecular mechanisms responsible for rapid phenotypic diversification, such as emergence of novel open reading frames (nORFs). In this study, we integrated transcriptomic and proteomic signatures from two tissues of two cichlids species, identified nORFs and performed evolutionary analysis on these nORF regions. Our results suggest that the time scale of speciation of the two species and evolutionary divergence of these nORF genomic regions are similar and indicate a potential role for these nORFs in speciation of the cichlid fishes. [ABSTRACT FROM AUTHOR]

Background: In primary care, multiple priorities and system pressures make closing the gap between evidence and practice challenging. Most implementation studies focus on single conditions, limiting generalisability. We compared an adaptable implementation package against an implementation control and assessed effects on adherence to four different evidence-based quality indicators.Methods and Findings: We undertook two parallel, pragmatic cluster-randomised trials using balanced incomplete block designs in general practices in West Yorkshire, England. We used 'opt-out' recruitment, and we randomly assigned practices that did not opt out to an implementation package targeting either diabetes control or risky prescribing (Trial 1); or blood pressure (BP) control or anticoagulation in atrial fibrillation (AF) (Trial 2). Within trials, each arm acted as the implementation control comparison for the other targeted indicator. For example, practices assigned to the diabetes control package acted as the comparison for practices assigned to the risky prescribing package. The implementation package embedded behaviour change techniques within audit and feedback, educational outreach, and computerised support, with content tailored to each indicator. Respective patient-level primary endpoints at 11 months comprised the following: achievement of all recommended levels of haemoglobin A1c (HbA1c), BP, and cholesterol; risky prescribing levels; achievement of recommended BP; and anticoagulation prescribing. Between February and March 2015, we recruited 144 general practices collectively serving over 1 million patients. We stratified computer-generated randomisation by area, list size, and pre-intervention outcome achievement. In April 2015, we randomised 80 practices to Trial 1 (40 per arm) and 64 to Trial 2 (32 per arm). Practices and trial personnel were not blind to allocation. Two practices were lost to follow-up but provided some outcome data. We analysed the intention-to-treat (ITT) population, adjusted for potential confounders at patient level (sex, age) and practice level (list size, locality, pre-intervention achievement against primary outcomes, total quality scores, and levels of patient co-morbidity), and analysed cost-effectiveness. The implementation package reduced risky prescribing (odds ratio [OR] 0.82; 97.5% confidence interval [CI] 0.67-0.99, p = 0.017) with an incremental cost-effectiveness ratio of £1,359 per quality-adjusted life year (QALY), but there was insufficient evidence of effect on other primary endpoints (diabetes control OR 1.03, 97.5% CI 0.89-1.18, p = 0.693; BP control OR 1.05, 97.5% CI 0.96-1.16, p = 0.215; anticoagulation prescribing OR 0.90, 97.5% CI 0.75-1.09, p = 0.214). No statistically significant effects were observed in any secondary outcome except for reduced co-prescription of aspirin and clopidogrel without gastro-protection in patients aged 65 and over (adjusted OR 0.62; 97.5% CI 0.39-0.99; p = 0.021). Main study limitations concern our inability to make any inferences about the relative effects of individual intervention components, given the multifaceted nature of the implementation package, and that the composite endpoint for diabetes control may have been too challenging to achieve.Conclusions: In this study, we observed that a multifaceted implementation package was clinically and cost-effective for targeting prescribing behaviours within the control of clinicians but not for more complex behaviours that also required patient engagement.Trial Registration: The study is registered with the ISRCTN registry (ISRCTN91989345). [ABSTRACT FROM AUTHOR]

Background: Clinical risk-scoring tools are increasingly recommended for use in general practice. Yet adoption of the tools has been variable and often low. Reasons for this have been explored, but medical students' perspectives have not previously been sought. Aim: To explore medical students' attitudes towards clinical risk-scoring tools. Methods: Qualitative, semi-structured interviews were conducted with eight medical students. Interviews were recorded, transcribed and analysed thematically. Results: Participants had a good understanding of the use of risk-scoring tools. They would trust them to enable evidence-based practice provided they are easy to use, not time-consuming and their results can help direct management. They were considered useful tools, especially for students and junior doctors. However, many believed the tools hold less value for experienced doctors. Their attitudes seem to have developed from discussions with clinicians, observation on placement, teaching received and exam content. Conclusion: This research recommends that implementation of risk-scoring tools will be increased if they are easier to use and if the belief that they hold less value for experienced doctors is challenged. The role of targeted teaching in changing these perceptions should be explored further, both for students and clinicians, who act as role models. [ABSTRACT FROM AUTHOR]

Background: Childhood obesity is a major public health concern. In the United Kingdom, a quarter of children are overweight or obese at age 5 years. Overweight and obese children are more likely to develop serious health issues such as diabetes later in life. Consequently, there is an urgent need for effective, early obesity prevention and intervention. This study investigated the impact of an 8‐week child obesity intervention—HENRY (Health Exercise Nutrition for the Really Young)—designed to help parents with preschool children develop the skills and knowledge needed to improve family lifestyle and well‐being. We were particularly interested in exploring the potential mechanisms by which HENRY may have a positive impact. Method: Focus groups (n = 7, total participants = 39) were completed with mothers attending the HENRY programme at one of seven locations across England. They took place within 2 weeks of programme completion. Follow‐up telephone interviews were completed with a subsample of participants (n = 10) between 17 and 21 weeks later. Results: Parents consistently reported enhanced self‐efficacy in terms of improved confidence in their ability to encourage healthier behaviours such as eating fruit and vegetables and increasing physical activity, and improvements to family health behaviours. Many changes were reportedly sustained at follow‐up. Data provided insights into the potential mechanisms that created the conditions for the positive changes. Participants described the importance of mutual support, being listened to by facilitators, and encouragement to identify their own ideas. Their comments indicated the success of a solution‐focused, strength‐based, partnership approach to supporting family lifestyle change. Conclusion: The results of this study contribute to the body of evidence suggesting that HENRY may have a positive impact on parenting and family lifestyle behaviour. Although data were collected in 2011, the findings contribute to an understanding of the components of effective obesity prevention in young children. [ABSTRACT FROM AUTHOR]

Background. Doctors have a special role in helping patients make lifestyle changes, and they are more credible and effective if they are role models. Yet few medical schools have incorporated lifestyle medicine into their curricula. We ascertained the influence of a lifestyle medicine curriculum during the first year of medical school. Methods. The curriculum, involving 140 students, consisted of one intensive day at medical school entry and 16 hours of teaching 8 months later. It addressed students' own lifestyle choices and topics related to lifestyle medicine. A survey was delivered at the beginning and end of the academic year. Results. A total of 114 students completed the first survey and 64 the second. They rated the course highly for personal and professional value. At baseline, students exhibited lifestyle behaviors typical for young adults and showed an appreciation of the physician's role in lifestyle change. However, over time they showed a significant reduction in quality of lifestyle, with increased stress, weight gain, and fast food consumption and less exercise. Conclusions. Although lifestyle medicine knowledge is valued by medical students, a 24-hour intensive lifestyle medicine curriculum delivered over 3 days appears to be ineffective in preventing worsening lifestyle behaviors over the course of the year. This is especially concerning as physicians are unlikely to provide effective guidance if they cannot sustain healthy behaviors themselves. [ABSTRACT FROM AUTHOR]

Background Patient and public involvement (PPI) is often an essential requirement for research funding. Distinctions can be drawn between clinical research, which generally focuses on patients, and implementation research, which generally focuses on health professional behaviour. There is uncertainty about the role of PPI in this latter field. We explored and defined the roles of PPI in implementation research to inform relevant good practice guidance. Methods We used a structured consensus process using a convenience sample panel of nine experienced PPI and two researcher members. We drew on available literature to identify 21 PPI research roles. The panel rated their agreement with roles independently online in relation to both implementation and clinical research. Disagreements were discussed at a face-to-face meeting prior to a second online rating of all roles. Median scores were calculated and a final meeting held to review findings and consider recommendations. Results Ten panellists completed the consensus process. For clinical research, there was strong support and consensus for the role of PPI throughout most of the research process. For implementation research, there were eight roles with consensus and strong support, seven roles with consensus but weaker support and six roles with no consensus. There were more disagreements relating to PPI roles in implementation research compared with clinical research. PPI was rated as contributing less to the design and management of implementation research than for clinical research. Conclusions The roles of PPI need to be tailored according to the nature of research to ensure authentic and appropriate involvement. We provide a framework to guide the planning, conduct and reporting of PPI in implementation research, and encourage further research to evaluate its use. [ABSTRACT FROM AUTHOR]

As the IEEE ComSoc History Committee celebrates the 70th Anniversary of the Communications Society, we reflect on the significant contributions of members to the technology of our world today, and look to the vision of a transformative, resilient, and sustainable future. With the new diversity and inclusion (D&I) initiatives, the History Committee, along with Women in Communications Engineering (WICE), will bring focus to women who, despite various efforts, remain underrepresented in the field of communications engineering, and among the entire IEEE membership. Even among science, technology, engineering, and mathematics (STEM) topics, communications engineering is behind in the representation of women. The new initiative will promote understanding of D&I and recognition of women through a variety of activities that will be covered in upcoming articles. [ABSTRACT FROM AUTHOR]

Background: There are widely recognised variations in the delivery and outcomes of healthcare but an incomplete understanding of their causes. There is a growing interest in using routinely collected ‘big data’ in the evaluation of healthcare. We developed a set of evidence-based ‘high impact’ quality indicators (QIs) for primary care and examined variations in achievement of these indicators using routinely collected data in the United Kingdom (UK). Methods: Cross-sectional analysis of routinely collected, electronic primary care data from a sample of general practices in West Yorkshire, UK (n = 89). The QIs covered aspects of care (including processes and intermediate clinical outcomes) in relation to diabetes, hypertension, atrial fibrillation, myocardial infarction, chronic kidney disease (CKD) and ‘risky’ prescribing combinations. Regression models explored the impact of practice and patient characteristics. Clustering within practice was accounted for by including a random intercept for practice. Results: Median practice achievement of the QIs ranged from 43.2% (diabetes control) to 72.2% (blood pressure control in CKD). Considerable between-practice variation existed for all indicators: the difference between the highest and lowest performing practices was 26.3 percentage points for risky prescribing and 100 percentage points for anticoagulation in atrial fibrillation. Odds ratios associated with the random effects for practices emphasised this; there was a greater than ten-fold difference in the likelihood of achieving the hypertension indicator between the lowest and highest performing practices. Patient characteristics, in particular age, gender and comorbidity, were consistently but modestly associated with indicator achievement. Statistically significant practice characteristics were identified less frequently in adjusted models. Conclusions: Despite various policy and improvement initiatives, there are enduring inappropriate variations in the delivery of evidence-based care. Much of this variation is not explained by routinely collected patient or practice variables, and is likely to be attributable to differences in clinical and organisational behaviour. [ABSTRACT FROM AUTHOR]

Background: There are recognised gaps between evidence and practice in general practice, a setting posing particular implementation challenges. We earlier screened clinical guideline recommendations to derive a set of 'high-impact' indicators based upon criteria including potential for significant patient benefit, scope for improved practice and amenability to measurement using routinely collected data. Here, we explore health professionals' perceived determinants of adherence to these indicators, examining the degree to which determinants were indicator-specific or potentially generalisable across indicators.Methods: We interviewed 60 general practitioners, practice nurses and practice managers in West Yorkshire, the UK, about adherence to four indicators: avoidance of risky prescribing; treatment targets in type 2 diabetes; blood pressure targets in treated hypertension; and anticoagulation in atrial fibrillation. Interview questions drew upon the Theoretical Domains Framework (TDF). Data were analysed using framework analysis.Results: Professional role and identity and environmental context and resources featured prominently across all indicators whilst the importance of other domains, for example, beliefs about consequences, social influences and knowledge varied across indicators. We identified five meta-themes representing more general organisational and contextual factors common to all indicators.Conclusions: The TDF helped elicit a wide range of reported determinants of adherence to 'high-impact' indicators in primary care. It was more difficult to pinpoint which determinants, if targeted by an implementation strategy, would maximise change. The meta-themes broadly underline the need to align the design of interventions targeting general practices with higher level supports and broader contextual considerations. However, our findings suggest that it is feasible to develop interventions to promote the uptake of different evidence-based indicators which share common features whilst also including content-specific adaptations. [ABSTRACT FROM AUTHOR]

Background: Recruitment of representative samples in primary care research is essential to ensure high-quality, generalizable results. This is particularly important for research using routinely recorded patient data to examine the delivery of care. Yet little is known about how different recruitment strategies influence the characteristics of the practices included in research.Objective: We describe three approaches for recruiting practices to data-sharing studies, examining differences in recruitment levels and practice representativeness.Methods: We examined three studies that included varying populations of practices from West Yorkshire, UK. All used anonymized patient data to explore aspects of clinical practice. Recruitment strategies were 'opt-in', 'mixed opt-in and opt-out' and 'opt-out'. We compared aggregated practice data between recruited and not-recruited practices for practice list size, deprivation, chronic disease management, patient experience and rates of unplanned hospital admission.Results: The opt-out strategy had the highest recruitment (80%), followed by mixed (70%) and opt-in (58%). Practices opting-in were larger (median 7153 versus 4722 patients, P = 0.03) than practices that declined to opt-in. Practices recruited by mixed approach were larger (median 7091 versus 5857 patients, P = 0.04) and had differences in the clinical quality measure (58.4% versus 53.9% of diabetic patients with HbA1c ≤ 59 mmol/mol, P < 0.01). We found no differences between practices recruited and not recruited using the opt-out strategy for any demographic or quality of care measures.Conclusion: Opt-out recruitment appears to be a relatively efficient approach to ensuring participation of typical general practices. Researchers should, with appropriate ethical safeguards, consider opt-out recruitment of practices for studies involving anonymized patient data sharing. [ABSTRACT FROM AUTHOR]

Background: There are recognised gaps between evidence and practice in general practice, a setting which provides particular challenges for implementation. We earlier screened clinical guideline recommendations to derive a set of 'high impact' indicators based upon criteria including potential for significant patient benefit, scope for improved practice and amenability to measurement using routinely collected data. We aim to evaluate the effectiveness and cost-effectiveness of a multifaceted, adaptable intervention package to implement four targeted, high impact recommendations in general practice.Methods/design: The research programme Action to Support Practice Implement Research Evidence (ASPIRE) includes a pair of pragmatic cluster-randomised trials which use a balanced incomplete block design. Clusters are general practices in West Yorkshire, United Kingdom (UK), recruited using an 'opt-out' recruitment process. The intervention package adapted to each recommendation includes combinations of audit and feedback, educational outreach visits and computerised prompts with embedded behaviour change techniques selected on the basis of identified needs and barriers to change. In trial 1, practices are randomised to adapted interventions targeting either diabetes control or risky prescribing and those in trial 2 to adapted interventions targeting either blood pressure control in patients at risk of cardiovascular events or anticoagulation in atrial fibrillation. The respective primary endpoints comprise achievement of all recommended target levels of haemoglobin A1c (HbA1c), blood pressure and cholesterol in patients with type 2 diabetes, a composite indicator of risky prescribing, achievement of recommended blood pressure targets for specific patient groups and anticoagulation prescribing in patients with atrial fibrillation. We are also randomising practices to a fifth, non-intervention control group to further assess Hawthorne effects. Outcomes will be assessed using routinely collected data extracted 1 year after randomisation. Economic modelling will estimate intervention cost-effectiveness. A process evaluation involving eight non-trial practices will examine intervention delivery, mechanisms of action and unintended consequences.Discussion: ASPIRE will provide 'real-world' evidence about the effects, cost-effectiveness and delivery of adapted intervention packages targeting high impact recommendations. By implementing our adaptable intervention package across four distinct clinical topics, and using 'opt-out' recruitment, our findings will provide evidence of wider generalisability.Trial Registration: ISRCTN91989345. [ABSTRACT FROM AUTHOR]

Background: Quality indicators (QIs) are an important tool for improving clinical practice and are increasingly being developed from evidence-based guideline recommendations. We aimed to identify, select and apply guideline recommendations to develop a set of QIs to measure the implementation of evidence-based practice using routinely recorded clinical data in United Kingdom (UK) primary care. Methods: We reviewed existing national clinical guidelines and QIs and used a four-stage consensus development process to derive a set of 'high impact' QIs relevant to primary care based upon explicit prioritisation criteria. We then field tested the QIs using remotely extracted, anonymised patient records from 89 randomly sampled primary care practices in the Yorkshire region of England. Results: Out of 2365 recommendations and QIs originally reviewed, we derived a set of 18 QIs (5 single, 13 composites -- comprising 2-9 individual recommendations) for field testing. QIs predominantly addressed chronic disease management, in particular diabetes, cardiovascular and renal disease, and included both processes and outcomes of care. Field testing proved to be critical for further refinement and final selection. Conclusions: We have demonstrated a rigorous and transparent methodology to develop a set of high impact, evidence-based QIs for primary care from clinical guideline recommendations. While the development process was successful in developing a limited set of QIs, it remains challenging to derive robust new QIs from clinical guidelines in the absence of established systems for routine, structured recording of clinical care. [ABSTRACT FROM AUTHOR]

Objective To explore factors that influence decision-making in relation to prenatal diagnostic testing (PDT) for inherited retinal disease (IRD). Method Semi-structured interviews were conducted with 50 adults with IRD, selected from a larger sample to provide a diversity of backgrounds and opinions on genetic testing. Interviews were transcribed verbatim and analysed using thematic analysis. Results Mostly participants supported PDT, believing that it would provide information to help them prepare for and plan the future care of the child and the potential for early access to emerging therapies. Opposition to PDT stemmed from its use to justify termination of pregnancy, with participants feeling that it was not justified as they retained a good quality of life despite their visual impairment. Participants raised concerns about the risk of PDT and the accuracy of the results. However, most suggested that it should be available as an option for others, but for specific reasons and not as a part of routine care. Conclusion The variation in attitudes towards PDT and uncertainty about the risk and accuracy of results suggest that individuals at risk of having a child with IRD should have access to genetic counselling to support decision making. © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This paper investigates the willingness of adults with inherited retinal disease to undergo and pay for diagnostic genetic testing in three hypothetical scenarios and to explore the factors that influence decision making. Fifty patients were presented with three scenarios whereby genetic testing provided increasing information: confirming the diagnosis and inheritance pattern alone, providing additional information on future visual function, and identifying in addition a new treatment which could stabilise their condition. Willingness to pay (WTP) was elicited using an iterative bidding game. Regression analysis was used to investigate the probability of agreeing to and paying for testing. Qualitative data were also reviewed to provide a comprehensive understanding of WTP and decision making. The majority of participants agreed to undergo genetic testing in each of the three scenarios. Scenario 2 was the least acceptable with 78% of participants agreeing to genetic testing. The probability of agreeing to genetic testing decreased with age. Between 72 and 96% of participants reported a WTP for genetic testing. Average WTP was £539, £1516, and £6895 for scenarios 1, 2, and 3 respectively. Older participants and participants with higher incomes were willing to pay more for testing. Qualitative data provided additional detail about the rationale behind participants' decisions. The study suggests that patients with inherited retinal disease were willing to undergo and to pay for diagnostic genetic testing, suggesting that they valued the information it may provide. However, several patients preferred not to receive prognostic information and were less willing to pay for genetic testing that yielded such detail. [ABSTRACT FROM AUTHOR]

Advances in sequencing technology and the movement of genetic testing into all areas of medicine will increase opportunities for molecular confirmation of a clinical diagnosis. For health-care professionals without formal genetics training, there is a need to know what patients understand about genetics and genetic testing and their information needs and preferences for the disclosure of genetic testing results. These topics were explored during face-to-face interviews with 50 adults with inherited retinal disease, selected in order to provide a diversity of opinions. Participants had variable understanding of genetics and genetic testing, including basic concepts such as inheritance patterns and the risk to dependents, and many did not understand the term 'genetic counselling'. Most were keen for extra information on the risk to others, the process for genetic testing and how to share the information with other family members. Participants were divided as to whether genetic testing should be offered at the time of the initial diagnosis or later. Many would prefer the results to be given by face-to-face consultation, supplemented by further information in a format accessible to those with visual impairment. Health-care professionals and either leaflets or websites of trusted agencies were the preferred sources of information. Permission should be sought for disclosure of genetic information to other family members. The information needs of many patients with inherited retinal disease appear to be unmet. An understanding of their information needs and preferences is required to help health-care professionals provide optimal services that meet patient expectations. [ABSTRACT FROM AUTHOR]

Background Cerebral small vessel disease causes lacunar stroke, and more recently has been implicated as a cause of depression. Factors causing reduced quality of life in small vessel disease, including the relative contributions of disability and depressive symptoms, remain uncertain. Methods One hundred patients with small vessel disease and 55 controls completed the Stroke-Specific Quality of Life scale. The protocol was repeated in 40 patients with the young-onset genetic form of small vessel disease, cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy, and 35 controls. Disability, activities of daily living, cognition and depression were measured. Results Quality of life was significantly lower in small vessel disease versus controls: mean (standard deviation), 196⋅8 (35⋅2) vs. 226⋅8 (15⋅3), P < ⋅0001. Depressive symptoms were the major predictor of quality of life, explaining 52⋅9% of variance. The only other independent predictor was disability, explaining an additional 18⋅4%. A similar pattern was found in the young-onset genetic group, with reduced quality of life 202⋅0 (29⋅7) vs. controls 228⋅6 (13⋅1) P < ⋅0001, and depressive symptoms accounting for 42⋅2% of variance. Disability explained an additional 17⋅6%. Relationships between depression and quality of life, and disability and quality of life were independent of one another. Conclusions Depressive symptoms, often unrecognized, are a major determinant of reduced quality of life in small vessel disease. They account for greater reduction than, and are independent of, disability. This relationship may reflect the proposed causal association between white matter disease and depression. Treatment of depressive symptoms might significantly improve quality of life in small vessel disease. [ABSTRACT FROM AUTHOR]

Childhood obesity has reached epidemic levels, yet many health professionals lack confidence in working with parents around lifestyle change. HENRY (Health Exercise Nutrition for the Really Young)aims to tackle this through training practitioners to work more effectively with parents of preschoolers around obesity and lifestyle issues.We evaluated the long-term impact of HENRY training on health professionals' knowledge, skills and confidence in tackling obesity prevention. All practitioners trained2007-11 (n=1601) were invited to complete an online survey. 237 emails (14.8%) were undeliverable;354 (26.0%) of the remainder completed the survey. A majority (67%) reported using knowledge and skills gained on a regular basis in their professional lives. Sessions on the importance of empathy and key parenting skills were considered particularly useful, with 78% and 74% respectively reporting regular use of these skills. Effects on respondents' personal lives were also reported: 61% applied the knowledge and skills at home, identifying for example, more shared family mealtimes and reduced portion sizes. The impact endures, with 71% of those undergoing training >12 months ago, stating that they continued to use concepts in their professional lives. The findings suggest that brief training can have a sustained impact on practitioners' professional and personal lives. [ABSTRACT FROM AUTHOR]

Twin studies have highlighted that a large proportion of variability in chronotype is accounted for by individual-specific environmental factors (non-shared environmental influences). However, little research has aimed to identify specific non-shared environmental influences on chronotype. Although epidemiological studies have shed light on possible environmental influences on chronotype, a substantial amount of research has highlighted the importance of genetic influences on exposure toward specific environments, a process termed gene-environment correlation. It is possible that associations between the environment and chronotype are in part determined by genetics, rather than being purely environmental in origin. One way of exploring the contribution of purely non-shared environmental components on associations between chronotype and the environment is to use the monozygotic twin differences design. This design allows us to tease apart the influences of genetics and the environment to identify purely environmental components. One hundred eighty-nine monozygotic twin pairs (mean age 19.81 years, SD = 1.26, range = 18-22 years, 66.1% female) completed the Horne and Östberg Morningness-Eveningness Questionnaire as a measure of chronotype and questionnaires assessing the following candidate non-shared environmental influences: dependent and independent negative life events, educational attainment, employment status, relationship status, deviant peers, affiliation with deviant peers, general health, smoking, drug use, and alcohol use. Linear regression analyses indicated the presence of gene-environment correlation for the majority of associations between chronotype and candidate environmental influences. When controlling for genetic and shared environmental effects, within monozygotic twin-pair differences in chronotype were associated with within monozygotic twin-pair differences in dependent negative life events (β = −0.27, p < 0.001), educational attainment (β = −0.14, p < 0.05), smoking status (β = 0.22, p < 0.01), and drug use (β = −0.16, p < 0.01). These results suggest that some of the association between these variables is purely environmental in nature. The associations between the remaining environmental variables and chronotype, however, may be intertwined with underlying genetic factors. These findings add to our understanding of genetic and environmental mechanisms underlying the biological clock. [ABSTRACT FROM PUBLISHER]

Background Positive behaviour support (PBS) is behaviour analysis applied in support of people with challenging behaviour. Questions have been raised as to PBS effectiveness, costs, and accessibility. Method Outcome studies meeting specified criteria for PBS were selected for review. All told, 12 outcome studies encompassing 423 cases were included. Results This review showed that PBS was effective with both severe and high-rate behaviour problems, was cost-effective, used a methodology that was easily trained and widely disseminated, and worked in institutional settings in which the most difficult problems are thought to be, as well as in the community. Conclusions The major implication of this review is that practitioners may be obligated to use PBS when faced with the need to develop a plan of support given the ethical principle of using the least restrictive method consistent with the right to effective treatment. [ABSTRACT FROM AUTHOR]

The article presents an editorial in which the authors present a research agenda based on topics in the special series of articles in the issue on positive behaviour support (PBS). Research recommendations include subjects such as behavioural episodic severity, comprehensive functional assessment (CFA), and crisis resolution.

Two-dimensional flood inundation models are widely used tools for flood hazard mapping and an essential component of statutory flood risk management guidelines in many countries. Yet, we still do not know how much physical complexity a flood inundation model needs for a given problem. Here, three two-dimensional explicit hydraulic models, which can be broadly defined as simulating diffusive, inertial or shallow water waves, have been benchmarked using test cases from a recent Environment Agency for England and Wales study, where results from industry models are also available. To ensure consistency, the three models were written in the same code and share subroutines for all but the momentum (flow) and time-stepping calculations. The diffusive type model required much longer simulation times than the other models, whilst the inertia model was the quickest. For flows that vary gradually in time, differences in simulated velocities and depths due to physical complexity were within 10% of the simulations from a range of industry models. Therefore, for flows that vary gradually in time, it appears unnecessary to solve the full two-dimensional shallow water equations. As expected, however, the simpler models were unable to simulate supercritical flows accurately. Finally, implications of the results for future model benchmarking studies are discussed in light of a number of subtle factors that were found to cause significant differences in simulations relative to the choice of model. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Ultradwarf bermudagrass [Cynodon dactylon (L.) Pers. x C. transvaalensis Burtt-Davy] cultivars require considerable field research to determine best management practices for successful long-term culture. A field study was conducted in 2004 and 2005 on an experimental 'TifEagle' bermudagrass putting green in Clemson, SC, to examine effects of plant growth regulators (PGRs) applied bimonthly and three mowing heights on turf performance. The PGRs included ethephon [(2-chloroethyl)phosphonic acid] at 1.91 kg a.i. ha-1, flurprimidol [α-(l-methylethyl)α-[4-(trifluoro-methoxy)phenyl]-5-pyrimidine-methonol] at 0.07 kg a.i. ha-1, trinexapac-ethyl [4-(cyclopropyl-ct-hydroxymethylene)-3,5-dioxo-cyclohexane carboxylic acid ethyl ester] at 0.0175 kg a.i. ha-1, all pairwise PGR combinations at half the individual rates, and a nontreated control. Turf was mowed five times weekly at 2.50, 3.25, or 4.00 mm. Lateral regrowth with ethephon and trinexapac-ethyl was comparable to nontreated turf, while flurprimidol impeded lateral regrowth ~25%. All three PGRs reduced dry clipping weights, with flurprimidol most effective (>50% each harvest) and ethephon least effective (maximum 17%). Turf quality for trinexapac-ethyl, ethephon, and flurprimidol was excellent (8.0-8.4), acceptable (6.8-7.1) and unacceptable (3.6-5.2), respectively. Compared to the control, root length density increased 33% with trinexapac-ethyl, unaffected byethephon, and reduced 25% with flurprimidol. Flurprimidol increased ball roll distances in morning (AM) and (PM) by 21 and 26 cm, respectively, trinexapac-ethyl provided increases of 5 and 10 cm, respectively, while ethephon had no effect, compared to the control. No evidence of synergistic effects was observed for PGR combinations. Raising mowing heights increased lateral regrowth, turf quality, and root length density but decreased ball roll distances. Best overall performance of TifEagle bermudagrass was achieved with trinexapac-ethyl, as it increased root length density, provided excellent turf quality, reduced vertical growth, did not impede lateral regrowth, and increased ball roll distances, compared to the control. [ABSTRACT FROM AUTHOR]

Research investigating the relationship between cognitive styles and sleep quality has focused on younger adults, despite insomnia being most prevalent in older adults. Improved knowledge of the psychological factors associated with disturbed sleep may help to improve therapies. Fifty-four adults aged 60-84 years reported on their sleep quality, pre-sleep arousal, dysfunctional beliefs about sleep and completed a catastrophising interview. In individual models, pre-sleep arousal, dysfunctional beliefs and the number of catastrophising steps all predicted self-reported sleep quality. Interviews revealed several worries of particular relevance to older adults, including fears about accidents, health and domestic management. These findings suggest that similar associations between cognitions and insomnia are present in older as in younger adults, but also that greater consideration should perhaps be paid to the content of the worries that are specific to this population. [ABSTRACT FROM AUTHOR]