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Aims:Heart failure (HF) is a global health burden and new strategies to achieve timely diagnosis and early intervention are urgently needed. Natriuretic peptide (NP) testing can be used to screen for left ventricular systolic dysfunction (LVSD), but evidence on test performance is mixed, and international HF guidelines differ in their recommendations. Our aim was to summarize the evidence on diagnostic accuracy of NP screening for LVSD in general and high-risk community populations and estimate optimal screening thresholds. Methods:We searched relevant databases up to August 2020 for studies with a screened community population of over 100 adults reporting NP performance to diagnose LVSD. Study inclusion, quality assessment, and data extraction were conducted independently and in duplicate. Diagnostic test meta-analysis used hierarchical summary receiver operating characteristic curves to obtain estimates of pooled accuracy to detect LVSD, with optimal thresholds obtained to maximize the sum of sensitivity and specificity. Results:Twenty-four studies were identified, involving 26 565 participants: eight studies in high-risk populations (at least one cardiovascular risk factor), 12 studies in general populations, and four in both high-risk and general populations combined. For detecting LVSD in screened high-risk populations with N-terminal prohormone brain natriuretic peptide (NT-proBNP), the pooled sensitivity was 0.87 [95% confidence interval (CI) 0.73–0.94] and specificity 0.84 (95% CI 0.55–0.96); for BNP, sensitivity was 0.75 (95% CI 0.65–0.83) and specificity 0.78 (95% CI 0.72–0.84). Heterogeneity between studies was high with variations in positivity threshold. Due to a paucity of high-risk studies that assessed NP performance at multiple thresholds, it was not possible to calculate optimal thresholds for LVSD screening in high-risk populations alone. To provide an indication of where the positivity threshold might lie, the pooled accuracy for LVSD screening in high-risk and general community populations were combined and gave an optimal cut-off of 311pg/mL [sensitivity 0.74 (95% CI 0.53–0.88), specificity 0.85 (95% CI 0.68–0.93)] for NT-proBNP and 49pg/mL [sensitivity 0.68 (95% CI 0.45–0.85), specificity 0.81 (0.67–0.90)] for BNP. Conclusions:Our findings suggest that in high-risk community populations NP screening may accurately detect LVSD, potentially providing an important opportunity for diagnosis and early intervention. Our study highlights an urgent need for further prospective studies, as well as an individual participant data meta-analysis, to more precisely evaluate diagnostic accuracy and identify optimal screening thresholds in specifically defined community-based populations to inform future guideline recommendations.

Background Unexpected weight loss is a presenting feature of cancer in primary care. Data from primary care are lacking to quantify how much weight loss over what period should trigger further investigation for cancer. This research aimed to quantify cancer diagnosis rates associated with measured weight change in people attending primary care. Methods Retrospective cohort study of primary care electronic health records data linked to the Surveillance, Epidemiology, and End Results cancer registry (Integrated healthcare delivery system in Washington State, United States). Multivariable Cox regression incorporating time varying covariates using splines to model non-linear associations (age, percentage weight change, and weight change interval). Fifty thousand randomly selected patients aged 40 years and over followed for up to 9 years (1 January 2006 to 31 December 2014). Outcome measures are hazard ratios (95% confidence intervals) to quantify the association between percentage weight change and cancer diagnosis for all cancers combined, individual cancer sites and stages; percentage risk of cancer diagnosis within 6 months of the end of each weight change episode; and the positive predictive value for cancer diagnosis. Results There were 43 302 included in the analysis after exclusions. Over 287 858 patient-years of follow-up, including 24 272 (56.1%) females, 23 980 (55.4%) aged 40 to 59 years, 15 113 (34.9%) 60 to 79 years, and 4209 (9.7%) aged 80 years and over. Adjusted hazard ratios (95% confidence interval) for cancer diagnosis in a 60 years old ranged from 1.04 (1.02 to 1.05, P < 0.001) for 1% weight loss to 1.44 (1.23 to 1.68, P < 0.001) for 10%. An independent linear association was observed between percentage weight loss and increasing cancer risk. The absolute risk of cancer diagnosis increased with increasing age (up to 85 years) and as the weight change measurement interval decreased ( Conclusions Weight loss is a sign of undiagnosed cancer regardless of the interval over which it occurs. Guidelines should resist giving an arbitrary cut-off for the interval of weight loss and focus on the percentage of weight loss and the patient's age. Future studies should focus on the association between diagnostic evaluation of weight change and risk of cancer mortality.

IntroductionOpioid prescribing trends have been investigated in many countries. However, the patterns of over-the-counter purchases of opioids without a prescription, such as codeine combinations, are mostly unknown.ObjectiveWe aimed to assess national sales and expenditure trends of over-the-counter codeine-containing products purchased in countries with available data over six years.MethodsWe conducted a retrospective observational study using electronic point-of-sale data from the human data science company, IQVIA, for countries that had such data, including Argentina, Belgium, Brazil, Bulgaria, Canada, Croatia, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Japan, Latvia, Lithuania, Mexico, The Netherlands, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Slovenia, South Africa, Spain, Switzerland, Thailand, the UK, and the USA. We calculated annual mean sales (dosage units per 1000 of the population) and public expenditure (GBP, £ per 1000 population) for each country between April 2013 and March 2019 and adjusted for data coverage reported by IQVIA. We quantified changes over time and the types of products sold.Results31.5 billion dosage units (adjusted: 42.8 billion dosage units) of codeine, costing £2.55 billion (adjusted: £3.68 billion), were sold over-the-counter in 31 countries between April 2013 and March 2019. Total adjusted sales increased by 11% (3911 dosage units/1000 population in 2013 to 4358 in 2019) and adjusted public expenditure increased by 72% (£263/1000 in 2013 to £451/1000 in 2019). Sales were not equally distributed; South Africa sold the most (36 mean dosage units/person), followed by Ireland (30 mean dosage units/person), France (20 mean dosage units/person), the UK (17.2 mean dosage units/person), and Latvia (16.8 mean dosage units/person). Types of products (n=569) and formulations (n=12) sold varied.ConclusionIn many parts of the world, substantial numbers of people may be purchasing and consuming codeine from over-the-counter products. Clinicians should ask patients about their use of over-the-counter products, and public health measures are required to improve the collection of sales data and the safety of such products.Study protocol pre-registrationhttps://osf.io/ay4mcThe pre-print version of this work is available on medRxiv:https://doi.org/10.1101/2021.04.21.21255888Key pointsCodeine is one of the most accessible pain medicines available worldwide, yet data on its use as an over-the-counter drug has been limited.We found that total sales and expenditure of over-the-counter products containing codeine increased from April 2013 to March 2019, but there was substantial variation in mean sales between countries and the coverage of data reported by IQVIA, with South Africa, France, Japan, the UK, and Poland accounting for 90% of all sales data.In countries with access to over-the-counter codeine products, sales data should be collected, made available, and reviewed to inform regulatory decisions and public health measures to ensure safety.

Background: Deprescribing of antihypertensive medications for older patients with normal blood pressure is recommended by some clinical guidelines, where the potential harms of treatment may outweigh the benefits. This study aimed to assess the cost-effectiveness of this approach. Methods: A Markov patient-level simulation was undertaken to model the effect of withdrawing one antihypertensive compared with usual care, over a life-time horizon. Model population characteristics were estimated using data from the OPTiMISE antihypertensive deprescribing trial, and the effects of blood pressure changes on outcomes were derived from the literature. Health-related quality of life was modeled in Quality-Adjusted Life Years (QALYs) and presented as costs per QALY gained. Results: In the base-case analysis, medication reduction resulted in lower costs than usual care (mean difference £185), but also lower QALYs (mean difference 0.062) per patient over a life-time horizon. Usual care was cost-effective at £2975 per QALY gained (more costly, but more effective). Medication reduction resulted more heart failure and stroke/TIA events but fewer adverse events. Medication reduction may be the preferred strategy at a willingness-to-pay of £20 000/QALY, where the baseline absolute risk of serious drug-related adverse events was ≥7.7% a year (compared with 1.7% in the base-case). Conclusions: Although there was uncertainty around many of the assumptions underpinning this model, these findings suggest that antihypertensive medication reduction should not be attempted in many older patients with controlled systolic blood pressure. For populations at high risk of adverse effects, deprescribing may be beneficial, but a targeted approach would be required in routine practice.

Background The Helicobacter Eradication Aspirin Trial (HEAT) is a multicentre, double blind, randomised controlled trial investigating whether Helicobacter (H.) pylori eradication reduces hospitalisation for peptic ulcer bleeding. Recruited participants were aged 60 and over and taking aspirin (≤325 mg daily) for at least four months prior to consent. Based on results of a pilot study, a sample size calculation predicted 6600 H. pylori-positive randomised participants would be required, from 33,000 volunteers, recruited from 170,000 invited patients. Methodology was therefore designed for recruitment of large numbers of patients from primary care using a novel electronic search tool, automated mail-out and electronic follow-up. Recruitment started in 2012 and completed in 2017. Methods All participants were recruited from GP practices, with assistance from the UK Clinical Research Network (UKCRN). H. pylori-positive participants were randomised to one week of eradication treatment or placebo. Recruitment was managed using a bespoke web-based database that communicated directly with a programmed search tool downloaded at participating practices. The primary endpoint is hospitalisation due to peptic ulcer bleeding. The trial will end when 87 adjudicated events have occurred, identified from searches of GP databases, review of secondary care admission data and mortality data, and reported events from randomised participants and GPs. Results HEAT has recruited participants from 1208 GP practices across the UK. Of the 188,875 invitation letters sent, 38,771 returned expressions of interest. Of these, 30,166 patients were consented to the trial, of whom 5355 H. pylori-positive participants (17.8% of those consented) were randomised. Mean age at consent was 73.1 ± 6.9 (SD) years and 72.2% of participants were male. Of the randomised (H. pylori-positive) participants, 531 have died (as of 17 Sep 2020); none of the deaths was due to trial treatment. Conclusion The HEAT trial methodology has demonstrated that recruitment of large numbers of patients from primary care is attainable, with the assistance of the UKCRN, and could be applied to other clinical outcomes studies. Trial registration ClinicalTrials.gov; registration number NCT01506986. Registered on 10 Jan 2012.

Background: Decline in kidney function can result in adverse health outcomes. The OxREN study has detailed baseline assessments from 884 participants ≥60 years. Aim: To determine the proportion of participants with decline in estimated glomerular filtration rate (eGFR), identify determinants of decline and determine proportions with chronic kidney disease (CKD) remission. Design and setting: Observational cohort study in UK primary care. Methods: Data were used from baseline and annual follow-up assessments to monitor change in kidney function. Rapid eGFR decline was defined as eGFR decrease >5 ml/min/1.73m2 /year, improvement as eGFR increase >5ml/min/1.73m2 /year and remission in those with CKD at baseline and eGFR>60 ml/min/1.73m2 during follow-up. Cox proportional hazard models were used to identify factors associated with eGFR decline. Results: In 686 participants with a median follow-up of 2.1 years, 164 (24%) evidenced rapid GFR decline, 185 (27%) experienced eGFR improvement and 82 of 394 (21%) meeting CKD stage 1-4 at baseline experienced remission. In the multivariable analysis, smoking status, higher systolic blood pressure and being known to have CKD at cohort entry were associated with rapid GFR decline. Those with CKD stage 3 at baseline were less likely to exhibit GFR decline compared with normal kidney function. Conclusions: This study established that 24% of people evidenced rapid GFR decline whereas 21% evidenced remission of CKD. People at risk of rapid GFR decline may benefit from closer monitoring and appropriate treatment to minimise risks of adverse outcomes, though only a small proportion meet the NICE criteria for referral to secondary care.

Funder: NIHR Cambridge Clinical Research Facility, Aims: Heart failure with preserved ejection fraction (HFpEF) accounts for half of all heart failure (HF), but low awareness and diagnostic challenges hinder identification in primary care. Our aims were to evaluate the recruitment and diagnostic strategy in the Optimise HFpEF cohort and compare with recent recommendations for diagnosing HFpEF. Methods and results: Patients were recruited from 30 primary care practices in two regions in England using an electronic screening algorithm and two secondary care sites. Baseline assessment collected clinical and patient‐reported data and diagnosis by history, assessment, and trans‐thoracic echocardiogram (TTE). A retrospective evaluation compared study diagnosis with H2FPEF score and HFA‐PEFF diagnostic algorithm. A total of 152 patients (86% primary care, mean age 78.5, 40% female) were enrolled; 93 (61%) had HFpEF confirmed. Most participants had clinical features of HFpEF, but those with confirmed HFpEF were more likely female, obese, functionally impaired, and symptomatic. Some echocardiographic findings were diagnostic for HFpEF, but no difference in natriuretic peptide levels were observed. The H2FPEF and HFA‐PEFF scores were not significantly different by group, although confirmed HFpEF cases were more likely to have scores indicating high probability of HFpEF. Conclusions: Patients with HFpEF in primary care are difficult to identify, and greater awareness of the condition, with clear diagnostic pathways and specialist support, are needed. Use of diagnostic algorithms and scores can provide systematic approaches to diagnosis but may be challenging to apply in older multi‐morbid patients. Where diagnostic uncertainty remains, pragmatic decisions are needed regarding the value of additional testing versus management of presumptive HFpEF.

© 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. Aim: To provide reliable survival estimates for people with chronic heart failure and explain variation in survival by key factors including age at diagnosis, left ventricular ejection fraction, decade of diagnosis, and study setting. Methods and results: We searched in relevant databases from inception to August 2018 for non-interventional studies reporting survival rates for patients with chronic or stable heart failure in any ambulatory setting. Across the 60 included studies, there was survival data for 1.5 million people with heart failure. In our random effects meta-analyses the pooled survival rates at 1 month, 1, 2, 5 and 10 years were 95.7% (95% confidence interval 94.3–96.9), 86.5% (85.4–87.6), 72.6% (67.0–76.6), 56.7% (54.0–59.4) and 34.9% (24.0–46.8), respectively. The 5-year survival rates improved between 1970–1979 and 2000–2009 across healthcare settings, from 29.1% (25.5–32.7) to 59.7% (54.7–64.6). Increasing age at diagnosis was significantly associated with a reduced survival time. Mortality was lowest in studies conducted in secondary care, where there were higher reported prescribing rates of key heart failure medications. There was significant heterogeneity among the included studies in terms of heart failure diagnostic criteria, participant co-morbidities, and treatment rates. Conclusion: These results can inform health policy and individual patient advanced care planning. Mortality associated with chronic heart failure remains high despite steady improvements in survival. There remains significant scope to improve prognosis through greater implementation of evidence-based treatments. Further research exploring the barriers and facilitators to treatment is recommended.

Background: Monitoring is the mainstay of chronic kidney disease management in primary care. There is little evidence on how best to monitor. Aim: To compare the effectiveness of eGFR derived from creatinine or cystatin C, to predict renal function decline among those with a recent eGFR of 30-89 ml/min/1.73m². Design and setting: Observational cohort study in UK primary care. Method: In 750 adult patients with a recent estimated glomerular filtration rate (eGFR) of 30-89 ml/min/1.73m² both creatinine and cystatin C were measured at seven study visits over two years. The primary outcome was change in eGFR derived from creatinine or cystatin C between 6 and 24 months. Results: Average change in eGFR was 0.51 ml/min/1.73m²/year or -2.35 ml/min/1.73m²/year when estimated by creatinine or cystatin C respectively. The c-statistic for predicting renal decline using creatinine-derived eGFR was 0.495 (95% CI 0.471 to 0.519). The equivalent c-statistic using cystatin C-derived eGFR was 0.497 (95% CI 0.468 to 0.525). Similar results were obtained when restricting analyses to those over or under 75 years, or with eGFR above 60 ml/min/1.73m2. In those with eGFR below 60 ml/min/1.73m2 cystatin C-derived eGFR was more predictive than creatinine-derived eGFR for future decline. Conclusion: In the primary analysis neither eGFR estimated from creatinine nor cystatin C predicted future change in kidney function, partly due to small changes during two years. In some secondary analyses there was a suggestion that cystatin C to estimate eGFR was a more useful biomarker, especially in those with baseline eGFR < 60 ml/min/1.73m2.

BackgroundThe Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE) trial has provided in-pandemic evidence of what does not work in the early primary care management of coronavirus-2019 disease (COVID-19). PRINCIPLE’s first finding was that azithromycin and doxycycline were not effective.AimTo explore the extent to which azithromycin and doxycycline were being used in-pandemic, and the scope for trial findings impacting on practice.Design and SettingWe compared crude rates of prescribing and respiratory tract infections (RTI) in 2020, the pandemic year, with 2019, using the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC).MethodsWe used a negative binomial model including age-band, gender, socioeconomic status, and NHS region to compare azithromycin and doxycycline lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), and influenza-like-illness (ILI) in 2020 with 2019; reporting incident rate ratios (IRR) between years and 95% confidence intervals (95%CI).ResultsAzithromycin prescriptions increased 7% in 2020 compared to 2019, whereas doxycycline decreased by 7%. Concurrently, LRTI and URTI incidence fell by over half (58.3% and 54.4% respectively) while ILI rose slightly (6.4%). The overall percentage of RTI prescribed azithromycin rose by 42.1% between 2019 and 2020, doxycycline increased by 33%.Our adjusted IRR showed azithromycin prescribing was 22% higher in 2020 (IRR=1.22, 95%CI:1.19-1.26, pConclusionPRINCIPLE trial flags scope for improvement in antimicrobial stewardship.

Findings: The NHS and ASC system have experienced tightening budgets and serious financial pressure, with historically low real-terms growth in health funding from central government and local authorities. Policymakers have tried to overcome these challenges with several policy innovations, but many still remain. With large-scale investment and reform, there is potential for the health and social care system to evolve into a modern service capable of dealing with the needs of an ageing population. However, if these challenges are not met, then it is set to continue struggling with a lack of appropriate facilities, an overstretched staff and a system not entirely appropriate for its patients.

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Azithromycin, an antibiotic with potential antiviral and anti-inflammatory properties, has been used to treat COVID-19, but evidence from community randomised trials is lacking. We aimed to assess the effectiveness of azithromycin to treat suspected COVID-19 among people in the community who had an increased risk of complications. Methods: In this UK-based, primary care, open-label, multi-arm, adaptive platform randomised trial of interventions against COVID-19 in people at increased risk of an adverse clinical course (PRINCIPLE), we randomly assigned people aged 65 years and older, or 50 years and older with at least one comorbidity, who had been unwell for 14 days or less with suspected COVID-19, to usual care plus azithromycin 500 mg daily for three days, usual care plus other interventions, or usual care alone. The trial had two coprimary endpoints measured within 28 days from randomisation: time to first self-reported recovery, analysed using a Bayesian piecewise exponential, and hospital admission or death related to COVID-19, analysed using a Bayesian logistic regression model. Eligible participants with outcome data were included in the primary analysis, and those who received the allocated treatment were included in the safety analysis. The trial is registered with ISRCTN, ISRCTN86534580. Findings: The first participant was recruited to PRINCIPLE on April 2, 2020. The azithromycin group enrolled participants between May 22 and Nov 30, 2020, by which time 2265 participants had been randomly assigned, 540 to azithromycin plus usual care, 875 to usual care alone, and 850 to other interventions. 2120 (94%) of 2265 participants provided follow-up data and were included in the Bayesian primary analysis, 500 participants in the azithromycin plus usual care group, 823 in the usual care alone group, and 797 in other intervention groups. 402 (80%) of 500 participants in the azithromycin plus usual care group and 631 (77%) of 823 participants in the usual care alone group reported feeling recovered within 28 days. We found little evidence of a meaningful benefit in the azithromycin plus usual care group in time to first reported recovery versus usual care alone (hazard ratio 1·08, 95% Bayesian credibility interval [BCI] 0·95 to 1·23), equating to an estimated benefit in median time to first recovery of 0·94 days (95% BCI −0·56 to 2·43). The probability that there was a clinically meaningful benefit of at least 1·5 days in time to recovery was 0·23. 16 (3%) of 500 participants in the azithromycin plus usual care group and 28 (3%) of 823 participants in the usual care alone group were hospitalised (absolute benefit in percentage 0·3%, 95% BCI −1·7 to 2·2). There were no deaths in either study group. Safety outcomes were similar in both groups. Two (1%) of 455 participants in the azothromycin plus usual care group and four (1%) of 668 participants in the usual care alone group reported admission to hospital during the trial, not related to COVID-19. Interpretation: Our findings do not justify the routine use of azithromycin for reducing time to recovery or risk of hospitalisation for people with suspected COVID-19 in the community. These findings have important antibiotic stewardship implications during this pandemic, as inappropriate use of antibiotics leads to increased antimicrobial resistance, and there is evidence that azithromycin use increased during the pandemic in the UK. Funding: UK Research and Innovation and UK Department of Health and Social Care.

Background The Oxford–Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) and Public Health England (PHE) are commencing their 54th season of collaboration at a time when SARS-CoV-2 infections are likely to be cocirculating with the usual winter infections. Objective The aim of this study is to conduct surveillance of influenza and other monitored respiratory conditions and to report on vaccine uptake and effectiveness using nationally representative surveillance data extracted from primary care computerized medical records systems. We also aim to have general practices collect virology and serology specimens and to participate in trials and other interventional research. Methods The RCGP RSC network comprises over 1700 general practices in England and Wales. We will extract pseudonymized data twice weekly and are migrating to a system of daily extracts. First, we will collect pseudonymized, routine, coded clinical data for the surveillance of monitored and unexpected conditions; data on vaccine exposure and adverse events of interest; and data on approved research study outcomes. Second, we will provide dashboards to give general practices feedback about levels of care and data quality, as compared to other network practices. We will focus on collecting data on influenza-like illness, upper and lower respiratory tract infections, and suspected COVID-19. Third, approximately 300 practices will participate in the 2020-2021 virology and serology surveillance; this will include responsive surveillance and long-term follow-up of previous SARS-CoV-2 infections. Fourth, member practices will be able to recruit volunteer patients to trials, including early interventions to improve COVID-19 outcomes and point-of-care testing. Lastly, the legal basis for our surveillance with PHE is Regulation 3 of the Health Service (Control of Patient Information) Regulations 2002; other studies require appropriate ethical approval. Results The RCGP RSC network has tripled in size; there were previously 100 virology practices and 500 practices overall in the network and we now have 322 and 1724, respectively. The Oxford–RCGP Clinical Informatics Digital Hub (ORCHID) secure networks enable the daily analysis of the extended network; currently, 1076 practices are uploaded. We are implementing a central swab distribution system for patients self-swabbing at home in addition to in-practice sampling. We have converted all our primary care coding to Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) coding. Throughout spring and summer 2020, the network has continued to collect specimens in preparation for the winter or for any second wave of COVID-19 cases. We have collected 5404 swabs and detected 623 cases of COVID-19 through extended virological sampling, and 19,341 samples have been collected for serology. This shows our preparedness for the winter season. Conclusions The COVID-19 pandemic has been associated with a groundswell of general practices joining our network. It has also created a permissive environment in which we have developed the capacity and capability of the national primary care surveillance systems and our unique public health institute, the RCGP and University of Oxford collaboration.

Importance: Deprescribing of antihypertensive medications is recommended for some older patients with polypharmacy and multi-morbidity where the benefits of continued treatment may not outweigh the harms. Objective: This study aimed to establish whether antihypertensive medication reduction is possible without significant changes in systolic blood pressure control or adverse events during a 12-week follow-up period. Design, Setting, and Participants: The OPtimising Treatment for MIld Systolic hypertension in the Elderly (OPTIMISE) study was a randomized, unblinded, non-inferiority trial conducted in 69 primary care sites in England. Participants were aged ≥80 years with systolic blood pressure, This work received joint funding from the National Institute for Health Research (NIHR) Oxford Collaboration for Leadership in Applied Health Research and Care (CLAHRC) at Oxford Health NHS Foundation Trust (ref: P2-501) and the NIHR School for Primary Care Research (SPCR; ref 335).

Background Valvular heart disease (VHD) occurs commonly in older patients (>65 years) but the majority is mild disease, which is of uncertain importance. Understanding the impact of VHD on mortality in this older group of patients would help determine its relevance and aid the appropriate use of healthcare resources. OxValve is a cohort study in Oxfordshire screening people aged 65 and over for VHD. Over 4,009 participants were recruited between August 2009 and May 2016 and screened using echocardiography to establish the presence and severity of VHD. AIMS To report survival in the OxValve cohort, and to investigate whether people with VHD are at increased risk of death. Methods The OxValve cohort was linked to Office for National Statistics mortality data to obtain date and cause of death. Cox regression was used to investigate the association of any VHD, VHD of significant severity, and VHD subtypes with all-cause and cause-specific mortality, adjusting for potential confounders including age, sex, socioeconomic status, smoking, and comorbidities. Results Linked mortality data was available for 3,511 OxValve participants up to September 2018 (median 5.85 years follow-up). VHD was present in 2,645 (75.3%) participants and of these 288 (8.2%) had significant VHD. In total, 311 (8.9%) participants had died. Cancer was the commonest cause of death (n=135), followed by cardiovascular disease (n=75) and respiratory disease (n=35). After adjustment for age and other covariates, mild to moderate VHD was not associated with increased all-cause mortality (HR 1.16, 95% CI: 0.89 to 1.50). However, VHD of significant severity (moderate or severe disease) was associated with a nearly two-fold higher risk of death overall (HR 1.92, 95% CI: 1:38 to 2.67) including increased CVD mortality (HR 2.25, 95% CI: 1.21 to 4.18). DISCUSSION Mild to moderate VHD was very common, but was not associated with increased mortality. Significant VHD was however associated with a two-fold reduction in survival. Further research is required to understand the natural history of VHD, how to identify those with progressive disease and when to intervene. Acknowledgement/Funding NIHR Biomedical Research Centre, Oxford

Background: Evidence for kidney function monitoring intervals in primary care is weak, and based mainly on expert opinion. In the absence of trials of monitoring strategies, an approach combining a model for the natural history of kidney function over time combined with a cost-effectiveness analysis offers the most feasible approach for comparing the effects of monitoring under a variety of policies. This study aimed to create a model for kidney disease progression using routinely collected measures of kidney function. Methods: This is an open cohort study of patients aged ≥18 years, registered at 643 UK general practices contributing to the Clinical Practice Research Datalink between 1 April 2005 and 31 March 2014. At study entry, no patients were kidney transplant donors or recipients, pregnant or on dialysis. Hidden Markov models for estimated glomerular filtration rate (eGFR) stage progression were fitted to four patient cohorts defined by baseline albuminuria stage; adjusted for sex, history of heart failure, cancer, hypertension and diabetes, annually updated for age. Results: Of 1,973,068 patients, 1,921,949 had no recorded urine albumin at baseline, 37,947 had normoalbuminuria (30mg/mmol). Estimated annual transition probabilities were 0.75–1.3%, 1.5–2.5%, 3.4–5.4% and 3.1–11.9% for each cohort, respectively. Misclassification of eGFR stage was estimated to occur in 12.1% (95%CI: 11.9–12.2%) to 14.7% (95%CI: 14.1–15.3%) of tests. Male gender, cancer, heart failure and age were independently associated with declining renal function, whereas the impact of raised blood pressure and glucose on renal function was entirely predicted by albuminuria. Conclusions: True kidney function deteriorates slowly over time, declining more sharply with elevated urine albumin, increasing age, heart failure, cancer and male gender. Consecutive eGFR measurements should be interpreted with caution as observed improvement or deterioration may be due to misclassification.

Objective\ud Self-management of hypertension can reduce and control blood pressure (BP) compared to clinic monitoring. However, self-management relies on patients following an algorithm which may be variably adhered to. This study reports fidelity of high-risk patients to the self-management algorithm set by the TASMIN-SR trial.\ud Methods\ud Patients with hypertension, above target clinic BP and one or more of stroke, diabetes, coronary heart disease or chronic kidney disease, were invited to self-monitor following an individualised self-titration algorithm. Home BP readings and medication change details were submitted monthly for 12 months. Readings downloaded from patients’ electronic monitors were compared to written submissions and protocol fidelity was assessed.\ud Results\ud 276 patients were randomised to self-management and 225 (82%) completed the required training sessions. Of these, 166 (74%) completed self-management. 11,385/12,707 (89.6%) submitted readings were accurate compared to corresponding downloaded monitor readings. Mean error rate was 5.2% per patient, which increased with age but not co-morbidities.\ud Patients made 475/683 (69.5%) algorithm recommended medication changes, equating to nearly three medication changes per patient. Mean systolic BP for patients who completed training and made all recommended changes dropped from 141mmHg (95% CI 138.26-144.46) to 121mmHg (95% CI 118.30-124.17mmHg) compared to 129mmHg (95% CI 125.27-136.73mmHg) for patients who made none.\ud Conclusion\ud Most patients randomised to self-management completed training; however, 36% of these had dropped out by 12 months. Self-monitoring was largely undertaken properly and accurately recorded. Fidelity with self-management was associated with lower achieved systolic BP. Successful implementation of self-management into daily practice requires careful training and should be accompanied by monitoring of fidelity.

There has been a longstanding problem of suboptimal use of anticoagulation in patients with atrial fibrillation (AF), however there is limited evidence relating to the period following the commencement of non-vitamin K antagonist oral anticoagulants (NOACs) in the UK. Using UK data from the GARFIELD_AF registry, we investigated the evolving pattern of antithrombotic therapy in newly diagnosed AF patients with ≥1 additional risk factor for stroke.

ABI : ankle–brachial (blood pressure) index ABPM : ambulatory blood pressure monitoring ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE-I : angiotensin-converting enzyme inhibitor ACS : acute coronary syndromes ADVANCE : Action in Diabetes and Vascular disease: PreterAx

Objectives: Consultation duration has previously been shown to be associated with patient, practitioner, and practice characteristics. However, previous studies were conducted outside the UK, considered only small numbers of GP consultations, or focused primarily on practitioner level characteristics. We aimed to determine the patient and practice level factors associated with duration of GP and nurse consultations in UK primary care. Design and setting: Cross sectional data were obtained from English general practices contributing to the Clinical Practice Research Datalink (CPRD) linked to data on patient deprivation and practice staffing, rurality, and Quality and Outcomes Framework (QOF) achievement. Participants: 218,304 patients, from 316 English general practices, consulting from 1st April 2013 to 31st March 2014. Analysis: Multilevel mixed effects models described the association between consultation duration and patient and practice-level factors (patient age, gender, smoking status, ethnic group, deprivation and practice rurality, number of full time equivalent GPs/nurses, list size, consultation rate, quintile of overall QOF achievement, and training status). Results: Mean duration of face-to-face GP consultations was 9.24 minutes and 5.32 minutes for telephone consultations. Nurse face-to-face and telephone consultations lasted 9.70 and 5.73 minutes on average, respectively. Longer GP consultation duration was associated with female patient gender, practice training status and older patient age. Shorter duration was associated with higher deprivation and consultation rate. Longer nurse consultation duration was associated with male patient gender, older patient age and ever smoking; and shorter duration with higher consultation rate. Observed differences in duration were small (e.g. GP consultations with female patients compared to male patients were 8 seconds longer on average). Conclusions: Small observed differences in consultation duration indicate that patients are treated similarly regardless of background. Increased consultation duration may be beneficial for older or comorbid patients, but the benefits and costs of increased consultation duration require further study.

© 2017 Elsevier B.V. Heart failure (HF) is a common condition affecting predominantly older people. Symptoms include breathlessness and fatigue, and can significantly reduce quality of life. HF rarely occurs in isolation, with most patients having several co-existing diseases requiring multiple medications. There is a large evidence base for treatment of HF with reduced ejection fraction, or HFrEF; however, many of the trials did not include older people with multimorbidity so their findings should be applied to this group with some caution. The evidence for treatment of HF with preserved ejection fraction, or HFpEF, is much less well established in all age groups. Older people with HF are usually managed in primary care with input from specialist HF teams when needed. General practitioners are trained to take a generalist approach, which allows them to deliver holistic, person-centred care. The wider multidisciplinary team is also important during the patient's HF journey, with a particular need to consider palliative care towards the end of life. This article summarises the important aspects of HF management in older people from the perspective of primary care.

Background Heart failure is a treatable condition but making a diagnosis can be challenging. Objective To evaluate the performance of a clinical decision rule (CDR) with or without a natriuretic peptide assay for identifying heart failure in symptomatic patients presenting to primary care. Design Prospective, observational, diagnostic validation study and economic evaluation. Setting Twenty-eight general practices in central England, UK. Participants Primary care patients aged ≥ 55 years presenting with recent new-onset shortness of breath, lethargy or peripheral ankle oedema of > 48 hours’ duration. Instrument The CDR included a clinical element (male, history of myocardial infarction, crepitations at the lung bases and oedema) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) blood test. The reference standard was an expert consensus panel of three cardiology specialists. Main outcome measure The main outcome measure was test performance of the CDR and the natriuretic peptide test alone, and in combination, in estimating sensitivity and specificity, positive predictive value (PPV) and negative predictive value (NPV) for a diagnosis of heart failure. Economic evaluation of a decision tree with a NHS/Personal Social Services perspective determined the cost per quality-adjusted life-year (QALY) gained. Results In total, 304 participants were recruited to the validation cohort. The mean age was 73.9 years (standard deviation 8.8 years) and 124 (40.8%) participants were male. In total, 104 [34.2%, 95% confidence interval (CI) 28.9% to 39.8%] had a confirmed diagnosis of heart failure. The CDR had a sensitivity of 90% (95% CI 83% to 95%), specificity of 46% (95% CI 39% to 53%), PPV of 46% (95% CI 39% to 53%) and NPV of 90% (95% CI 83% to 95%). NT-proBNP level alone with a cut-off point of Conclusions Natriuretic peptide testing alone performed as well as the validated CDR in determining which patients presenting with symptoms went on to have a diagnosis of heart failure. The current NT-proBNP cut-off point of 400 pg/ml used in the UK is too high and means that one in five patients with heart failure may not be appropriately referred for further investigation and diagnosis, but this threshold was cost-effective in the REFer for EchocaRdiogram (REFER) trial. The study found only three patients with heart failure with reduced ejection fraction (HFREF), which might limit the benefits of early detection. The other diagnostic strategies with lower NT-proBNP referral levels become more cost-effective as the proportion of HFREF patients increases. International consensus on the optimal cut-off point for natriuretic peptide testing in patients with symptoms suggestive of heart failure should be sought. Trial registration Current Controlled Trials ISRCTN17635379. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

Improvement of outcomes for heart failure patients is an important goal. Sudden death in heart failure is common, but its causes are not well elucidated. Although the evidence base is limited, the combination of venous stasis, immobility and a hypercoagulable state suggest an increased venous thromboembolism risk, which in turn could lead to sudden death. Recent well conducted, randomised trials show that acutely ill hospitalised patients, including those with severe heart failure, are at moderate risk of venous thromboembolism, similar to the risk experienced by some surgical groups. They also show that the risk of venographically detected deep vein thrombosis can be reduced with antithrombotic prophylaxis. Recent consensus guidelines have introduced thromboprophylaxis recommendations that include heart failure as a major component. Several large clinical trials are ongoing that will help to define the effect of thromboprophylaxis on 'hard' clinical end points such as mortality.

INTRODUCTION: Chronic kidney disease (CKD) diagnosed with objective measures of kidney damage and function has been recognised as a major public health burden. Independent of age, sex, ethnicity and comorbidity, strong associations exist between cardiovascular disease, mortality, morbidity and CKD, defined by reduced glomerular filtration rate and increased urinary albumin excretion. Detection of CKD within the population is therefore a priority for health systems. METHODS AND ANALYSIS: 15 000 patients aged 60 years or over meeting the inclusion criteria will be invited to the study. Recruitment will be stratified to represent the distribution of socioeconomic position in the UK general population. Patients will be excluded if terminally ill (expected survival