Search

Background: There has been a continued trend towards undertaking primary care-based research but the characteristics and generalizability of practices that participate in such research are not well known. Objective: To compare research active and non-active practices in terms of practice demographics, disease prevalence and quality scores from the Quality and Outcomes Framework. Design: Cross-sectional survey using publicly available data. Setting: A total of 973 general practices from the West Midlands, UK. Main Outcome Measures: Practice population characteristics, research status, disease prevalence, clinical and non-clinical quality scores. Results: Of 973 practices, 298 (31%) were defined as research active. Research active practices had younger populations (% over 65: 15.2% versus 16.2%, z = 3.95, P < 0.0001) compared to non-research active practices, were larger [median list size 6123 (interquartile range, IQR, 3642-9691) versus 4059 (IQR 2675-7060) z = 6.96, P < 0.0001] and more likely to be in deprived areas [median Townsend quintile 5 (IQR 3-5) versus 4 (IQR 3-5), z = 3.23, P = 0.001]. Disease prevalence was similar in both research active and non-active practices but the former attained higher median quality scores for both clinical [research active 534/550 (IQR 508-546) versus non-research active 525/550 (IQR 483-542) z = 4.00, P < 0.0001] and non-clinical [310/320 (IQR 283-319) versus 296/320 (IQR 265-314), z = 5.76, P < 0.0001] areas. Conclusion: General practices which participate in research are larger and located in more deprived areas than non-research active practices but disease prevalence is similar and research practices attain only modestly higher quality points. Research in research active practices is likely to be generalizable to the wider primary care community. [ABSTRACT FROM AUTHOR]

Abstract: Background: Atrial fibrillation and hypertension are two common conditions in the elderly, associated with significant morbidity and mortality. Little information is available regarding the epidemiology of hypertension in elderly patients with atrial fibrillation. Subjects and methods: A secondary analysis of data from the Birmingham Atrial Fibrillation Treatment of the Aged study, a randomised controlled trial of thrombo-prophylaxis in atrial fibrillation in a primary care population. The study population comprised patients aged 75 and over with electrocardiogram (ECG) confirmed atrial fibrillation. Blood pressure was recorded in the general practice surgery on two occasions using standardised methods. History of hypertension was sought from the medical records and from asking the patient. Results: 3059 subjects had ECG confirmed atrial fibrillation. The prevalence of a history of hypertension in this group was 57.5%. The mean systolic blood pressure was 141 mmHg (standard deviation: 21 mmHg) in men and 144 mmHg (22 mmHg) in women. The mean diastolic blood pressure was 79 mmHg (12 mmHg) in men and 80 mmHg in women (12 mmHg). The mean systolic blood pressure was slightly lower than that of the general population aged 75 and over, but the mean diastolic blood pressure was significantly higher in patients in atrial fibrillation (by 8 mmHg). Among the patients with a diagnosis of hypertension, 86.5% were on blood pressure lowering medications. Conclusions: Hypertension is more commonly diagnosed in older patients with atrial fibrillation than in the general population. The mean systolic blood pressure is slightly lower, but the mean diastolic blood pressure substantially higher in older patients in atrial fibrillation, compared to the general population. [Copyright &y& Elsevier]

Background: Chronic kidney disease (CKD) is common and increasing in prevalence. Cardiovascular disease (CVD) is a major cause of morbidity and death in CKD, though of a different phenotype to the general CVD population. Few therapies have proved effective in modifying the increased CVD risk or rate of renal decline in CKD. There are accumulating data that aldosterone receptor antagonists (ARA) may offer cardio-protection and delay renal impairment in patients with the CV phenotype in CKD. The use of ARA in CKD has therefore been increasingly advocated. However, no large study of ARA with renal or CVD outcomes is underway.Methods: The study is a prospective randomised open blinded endpoint (PROBE) trial set in primary care where patients will mainly be identified by their GPs or from existing CKD lists. They will be invited if they have been formally diagnosed with CKD stage 3b or there is evidence of stage 3b CKD from blood results (eGFR 30-44 mL/min/1.73 m2) and fulfil the other inclusion/exclusion criteria. Patients will be randomised to either spironolactone 25 mg once daily in addition to routine care or routine care alone and followed-up for 36 months.Discussion: BARACK D is a PROBE trial to determine the effect of ARA on mortality and cardiovascular outcomes (onset or progression of CVD) in patients with stage 3b CKD.Trial Registration: EudraCT: 2012-002672-13ISRTN: ISRCTN44522369. [ABSTRACT FROM AUTHOR]

Background: Evidence for the effect of favipiravir treatment of acute COVID-19 on recovery, hospital admissions and longer-term outcomes in community settings is limited., Methods: In this multicentre. open-label, multi-arm, adaptive platform randomised controlled trial participants aged ≥18 years in the community with a positive test for SARS-CoV-2 and symptoms lasting ≤14 days were randomised to: usual care; usual care plus favipiravir tablets (loading dose of 3600 mg in divided doses on day one, then 800 mg twice a day for four days); or, usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery and hospitalisation/death related to COVID-19, within 28 days, analysed using Bayesian models. Recovery at six months was the primary longer-term outcome., Trial Registration: ISRCTN86534580., Findings: The primary analysis model included 8811 SARS-CoV-2 positive mostly COVID vaccinated participants, randomised to favipiravir (n = 1829), usual care (n = 3256), and other treatments (n = 3726). Time to self-reported recovery was shorter in the favipiravir group than usual care (estimated hazard ratio 1·23 [95% credible interval 1·14 to 1·33]), a reduction of 2·98 days [1·99 to 3·94] from 16 days in median time to self-reported recovery for favipiravir versus usual care alone. COVID-19 related hospitalisations/deaths were similar (estimated odds ratio 0·99 [0·61 to 1·61]; estimated difference 0% [-0·9% to 0·6%]). 14 serious adverse events occurred in the favipiravir group and 4 in usual care. By six months, the proportion feeling fully recovered was 74·9% for favipiravir versus 71·3% for usual care (RR = 1·05, [1·02 to 1·08])., Interpretation: In this open-label trial in a largely vaccinated population with COVID-19 in the community, favipiravir did not reduce hospital admissions, but shortened time to recovery and had a marginal positive impact on long term outcomes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Saville, Berry, Detry, Fitzgerald and Saunders report grants from The University of Oxford, for the Sponsor's grant from the UK NIHR, for statistical design and analyses for the PRINCIPLE trial during the conduct of the study. Prof de Lusignan is Director of the Oxford-RCGP Research and Surveillance Centre and reports that through his University he has had grants outside the submitted work from AstraZeneca, GSK, Sanofi, Seqirus and Takeda for vaccine related research, and membership of advisory boards for AstraZeneca, Sanofi and Seqirus. Profs Hobbs and Butler reports grants from UKRI, during the conduct of the study. All other authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Chronic Kidney Disease (CKD) is a common health problem, associated with increased risk of cardiovascular disease (CVD), end stage kidney disease (ESKD), and premature death. A third of people aged≥70 years have CKD, many of whom are undiagnosed, but little is known about the value of screening., Aim: To compare the risk of adverse health outcomes between people with an existing diagnosis of CKD and those identified on screening. To identify factors associated with mortality in CKD., Design & Setting: Prospective cohort study of 892 primary care patients aged≥60 years with CKD (existing and screening detected) in Oxfordshire, with data linkage to civil death registry and secondary care., Method: Hazard Ratios (HR) and 95% Confidence Intervals (CI) were estimated using Cox proportional-hazard models to compare the risk of all-cause mortality, hospitalisation, CVD, ESKD separately, and as a composite between CKD groups, as well as to identify factors associated with mortality., Results: After a median follow-up of 3-5 years, 49 people died, 493 were hospitalised, 57 had an incident CVD event, and 0 had an ESKD event. There was no difference in the composite outcome between those existing CKD and those identified on screening (HR 0.94, CI 0.67-1.33). Older age (HR 1.10, CI 1.06-1.15), male sex (HR 2.31, CI 1.26-4.24), and heart failure (HR 5.18, CI 2.45-10.97) were associated with increased risk of death., Conclusion: Screening older people for CKD may be of value, as their risk of short-term mortality, hospitalisation, and CVD is comparable to people routinely diagnosed. Larger studies with longer follow-up in more diverse and representative populations of older adults are needed to corroborate these findings., (Copyright © 2024, The Authors.)

IntroductionRespiratory sentinel surveillance systems leveraging computerised medical records (CMR) use phenotyping algorithms to identify cases of interest, such as acute respiratory infection (ARI). The Oxford-Royal College of General Practitioners Research and Surveillance Centre (RSC) is the English primary care-based sentinel surveillance network.AimThis study describes and validates the RSC's new ARI phenotyping algorithm.MethodsWe developed the phenotyping algorithm using a framework aligned with international interoperability standards. We validated our algorithm by comparing ARI events identified during the 2022/23 influenza season in England through use of both old and new algorithms. We compared clinical codes commonly used for recording ARI.ResultsThe new algorithm identified an additional 860,039 cases and excluded 52,258, resulting in a net increase of 807,781 cases (33.84%) of ARI compared to the old algorithm, with totals of 3,194,224 cases versus 2,386,443 cases. Of the 860,039 newly identified cases, the majority (63.7%) were due to identification of symptom codes suggestive of an ARI diagnosis not detected by the old algorithm. The 52,258 cases incorrectly identified by the old algorithm were due to inadvertent identification of chronic, recurrent, non-infectious and other non-ARI disease.ConclusionWe developed a new ARI phenotyping algorithm that more accurately identifies cases of ARI from the CMR. This will benefit public health by providing more accurate surveillance reports to public health authorities. This new algorithm can serve as a blueprint for other CMR-based surveillance systems wishing to develop similar phenotyping algorithms.

Background: The evidence for whether ivermectin impacts recovery, hospital admissions, and longer-term outcomes in COVID-19 is contested. The WHO recommends its use only in the context of clinical trials., Methods: In this multicentre, open-label, multi-arm, adaptive platform randomised controlled trial, we included participants aged ≥18 years in the community, with a positive SARS-CoV-2 test, and symptoms lasting ≤14 days. Participants were randomised to usual care, usual care plus ivermectin tablets (target 300-400 μg/kg per dose, once daily for 3 days), or usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery, and COVID-19 related hospitalisation/death within 28 days, analysed using Bayesian models. Recovery at 6 months was the primary, longer term outcome., Trial Registration: ISRCTN86534580., Findings: The primary analysis included 8811 SARS-CoV-2 positive participants (median symptom duration 5 days), randomised to ivermectin (n = 2157), usual care (n = 3256), and other treatments (n = 3398) from June 23, 2021 to July 1, 2022. Time to self-reported recovery was shorter in the ivermectin group compared with usual care (hazard ratio 1·15 [95% Bayesian credible interval, 1·07 to 1·23], median decrease 2.06 days [1·00 to 3·06]), probability of meaningful effect (pre-specified hazard ratio ≥1.2) 0·192). COVID-19-related hospitalisations/deaths (odds ratio 1·02 [0·63 to 1·62]; estimated percentage difference 0% [-1% to 0·6%]), serious adverse events (three and five respectively), and the proportion feeling fully recovered were similar in both groups at 6 months (74·3% and 71·2% respectively (RR = 1·05, [1·02 to 1·08]) and also at 3 and 12 months., Interpretation: Ivermectin for COVID-19 is unlikely to provide clinically meaningful improvement in recovery, hospital admissions, or longer-term outcomes. Further trials of ivermectin for SARS-Cov-2 infection in vaccinated community populations appear unwarranted., Funding: UKRI/National Institute of Health Research (MC&#95;PC&#95;19079)., Competing Interests: Declaration of Competing Interest Drs. Saville, Berry, Detry, Fitzgerald and Saunders report grants from The University of Oxford, for the Sponsor's grant from the UK NIHR, for statistical design and analyses for the PRINCIPLE trial during the conduct of the study. Prof de Lusignan is Director of the Oxford-RCGP Research and Surveillance Centre and reports that through his University he has had grants outside the submitted work from AstraZeneca, GSK, Sanofi, Seqirus and Takeda for vaccine related research, and membership of advisory boards for AstraZeneca, Sanofi and Seqirus. Profs Hobbs and Butler report grants from UKRI, during the conduct of the study. All other authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: In people with heart failure (HF), a high body mass index (BMI) has been linked with better outcomes ('obesity paradox'), but there is limited evidence in community populations across long-term follow-up. We aimed to examine the association between BMI and long-term survival in patients with HF in a large primary care cohort., Methods: We included patients with incident HF aged ≥45 years from the Clinical Practice Research Datalink (2000-2017). We used Kaplan-Meier curves, Cox regression and penalised spline methods to assess the association of pre-diagnostic BMI, based on WHO classification, with all-cause mortality., Results: There were 47 531 participants with HF (median age 78.0 years (IQR 70-84), 45.8% female, 79.0% white ethnicity, median BMI 27.1 (IQR 23.9-31.0)) and 25 013 (52.6%) died during follow-up. Compared with healthy weight, people with overweight (HR 0.78, 95% CI 0.75 to 0.81, risk difference (RD) -4.1%), obesity class I (HR 0.76, 95% CI 0.73 to 0.80, RD -4.5%) and class II (HR 0.76, 95% CI 0.71 to 0.81, RD -4.5%) were at decreased risk of death, whereas people with underweight were at increased risk (HR 1.59, 95% CI 1.45 to 1.75, RD 11.2%). In those underweight, this risk was greater among men than women (p value for interaction=0.02). Class III obesity was associated with increased risk of all-cause mortality compared with overweight (HR 1.23, 95% CI 1.17 to 1.29)., Conclusion: The U-shaped relationship between BMI and long-term all-cause mortality suggests a personalised approach to identifying optimal weight may be needed for patients with HF in primary care. Underweight people have the poorest prognosis and should be recognised as high-risk., Competing Interests: Competing interests: CJT reports personal fees and non-financial support from Roche outside the submitted work. All other authors report no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Antihypertensives reduce the risk of cardiovascular disease but are also associated with harms including acute kidney injury (AKI). Few data exist to guide clinical decision making regarding these risks., Aim: To develop a prediction model estimating the risk of AKI in people potentially indicated for antihypertensive treatment., Design and Setting: Observational cohort study using routine primary care data from the Clinical Practice Research Datalink (CPRD) in England., Method: People aged ≥40 years, with at least one blood pressure measurement between 130 mmHg and 179 mmHg were included. Outcomes were admission to hospital or death with AKI within 1, 5, and 10 years. The model was derived with data from CPRD GOLD ( n = 1 772 618), using a Fine-Gray competing risks approach, with subsequent recalibration using pseudo-values. External validation used data from CPRD Aurum ( n = 3 805 322)., Results: The mean age of participants was 59.4 years and 52% were female. The final model consisted of 27 predictors and showed good discrimination at 1, 5, and 10 years (C-statistic for 10-year risk 0.821, 95% confidence interval [CI] = 0.818 to 0.823). There was some overprediction at the highest predicted probabilities (ratio of observed to expected event probability for 10-year risk 0.633, 95% CI = 0.621 to 0.645), affecting patients with the highest risk. Most patients (>95%) had a low 1- to 5-year risk of AKI, and at 10 years only 0.1% of the population had a high AKI and low CVD risk., Conclusion: This clinical prediction model enables GPs to accurately identify patients at high risk of AKI, which will aid treatment decisions. As the vast majority of patients were at low risk, such a model may provide useful reassurance that most antihypertensive treatment is safe and appropriate while flagging the few for whom this is not the case., (© The Authors.)

Background: Analysis of circulating tumour DNA could stratify cancer risk in symptomatic patients. We aimed to evaluate the performance of a methylation-based multicancer early detection (MCED) diagnostic test in symptomatic patients referred from primary care., Methods: We did a multicentre, prospective, observational study at National Health Service (NHS) hospital sites in England and Wales. Participants aged 18 or older referred with non-specific symptoms or symptoms potentially due to gynaecological, lung, or upper or lower gastrointestinal cancers were included and gave a blood sample when they attended for urgent investigation. Participants were excluded if they had a history of or had received treatment for an invasive or haematological malignancy diagnosed within the preceding 3 years, were taking cytotoxic or demethylating agents that might interfere with the test, or had participated in another study of a GRAIL MCED test. Patients were followed until diagnostic resolution or up to 9 months. Cell-free DNA was isolated and the MCED test performed blinded to the clinical outcome. MCED predictions were compared with the diagnosis obtained by standard care to establish the primary outcomes of overall positive and negative predictive value, sensitivity, and specificity. Outcomes were assessed in participants with a valid MCED test result and diagnostic resolution. SYMPLIFY is registered with ISRCTN (ISRCTN10226380) and has completed follow-up at all sites., Findings: 6238 participants were recruited between July 7 and Nov 30, 2021, across 44 hospital sites. 387 were excluded due to staff being unable to draw blood, sample errors, participant withdrawal, or identification of ineligibility after enrolment. Of 5851 clinically evaluable participants, 376 had no MCED test result and 14 had no information as to final diagnosis, resulting in 5461 included in the final cohort for analysis with an evaluable MCED test result and diagnostic outcome (368 [6·7%] with a cancer diagnosis and 5093 [93·3%] without a cancer diagnosis). The median age of participants was 61·9 years (IQR 53·4-73·0), 3609 (66·1%) were female and 1852 (33·9%) were male. The MCED test detected a cancer signal in 323 cases, in whom 244 cancer was diagnosed, yielding a positive predictive value of 75·5% (95% CI 70·5-80·1), negative predictive value of 97·6% (97·1-98·0), sensitivity of 66·3% (61·2-71·1), and specificity of 98·4% (98·1-98·8). Sensitivity increased with increasing age and cancer stage, from 24·2% (95% CI 16·0-34·1) in stage I to 95·3% (88·5-98·7) in stage IV. For cases in which a cancer signal was detected among patients with cancer, the MCED test's prediction of the site of origin was accurate in 85·2% (95% CI 79·8-89·3) of cases. Sensitivity 80·4% (95% CI 66·1-90·6) and negative predictive value 99·1% (98·2-99·6) were highest for patients with symptoms mandating investigation for upper gastrointestinal cancer., Interpretation: This first large-scale prospective evaluation of an MCED diagnostic test in a symptomatic population demonstrates the feasibility of using an MCED test to assist clinicians with decisions regarding urgency and route of referral from primary care. Our data provide the basis for a prospective, interventional study in patients presenting to primary care with non-specific signs and symptoms., Funding: GRAIL Bio UK., Competing Interests: Declaration of interests BDN and MRM receive institutional research funding from GRAIL. MRM reports grants from Roche, Astrazeneca, BMS, Infinitopes, Immunocore, and study fees from BMS, Pfizer, MSD, Regeneron, BiolineRx, Replimune and Novartis outside of the submitted work. HK, KNK, SH, KR, YL, and HN are employees of GRAIL. HK, KNK, SH, KR, and YL hold stock in Illumina. HK reports a leadership position with GRAIL. DH reports a leadership role with CanSense, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: People with multiple health conditions are more likely to have poorer health outcomes and greater care and service needs; a reliable measure of multimorbidity would inform management strategies and resource allocation., Aim: To develop and validate a modified version of the Cambridge Multimorbidity Score in an extended age range, using clinical terms that are routinely used in electronic health records across the world (Systematized Nomenclature of Medicine - Clinical Terms, SNOMED CT)., Design and Setting: Observational study using diagnosis and prescriptions data from an English primary care sentinel surveillance network between 2014 and 2019., Method: In this study new variables describing 37 health conditions were curated and the associations modelled between these and 1-year mortality risk using the Cox proportional hazard model in a development dataset ( n = 300 000). Two simplified models were then developed - a 20-condition model as per the original Cambridge Multimorbidity Score and a variable reduction model using backward elimination with Akaike information criterion as the stopping criterion. The results were compared and validated for 1-year mortality in a synchronous validation dataset ( n = 150 000), and for 1-year and 5-year mortality in an asynchronous validation dataset ( n = 150 000)., Results: The final variable reduction model retained 21 conditions, and the conditions mostly overlapped with those in the 20-condition model. The model performed similarly to the 37- and 20-condition models, showing high discrimination and good calibration following recalibration., Conclusion: This modified version of the Cambridge Multimorbidity Score allows reliable estimation using clinical terms that can be applied internationally across multiple healthcare settings., (© The Authors.)

Background: During left-sided heart failure (HF), left atrial and pulmonary venous pressure increase, which may lead to pulmonary congestion. Previous cohort studies, examining participants with symptomatic HF or rheumatic heart disease, suggest a relationship between increased left atrial pressure (LAP) and fractional exhaled nitric oxide (FeNO)., Aim: To examine the strength of association between FeNO and echocardiographic assessment of LAP by the E/e' ratio, to determine if FeNO could be used to identify those with elevated LAP., Design & Setting: This cross-sectional cohort study examined a subset of the OxVALVE cohort aged ≥65 years. Data collection was undertaken in primary care practices in central England., Method: Each participant underwent a focused cardiovascular history and clinical examination. Standard transthoracic echocardiographic (TTE) assessment was performed on all participants, with the E/e' ratio calculated to obtain a validated surrogate of LAP. FeNO was measured in 227 participants., Results: FeNO was higher in males compared with females and no different in participants with asthma, chronic obstructive pulmonary disease (COPD), or those using inhaled steroids. Participants with a high E/e' (>14) were older, with a higher proportion of females than males. There was no relationship between E/e' and FeNO, either when measured as a continuous variable or in the group with high E/e'., Conclusion: FeNO was not found to be an accurate predictor of elevated LAP in a primary care setting., (Copyright © 2022, The Authors.)

Background: In England, most prescribing of direct-acting oral anticoagulants for atrial fibrillation (AF) is in primary care. However, there remain gaps in our understanding of dosage and disparities in use. We aimed to describe trends in direct oral anticoagulant (DOAC) prescribing, including dose reduction in people with renal impairment and other criteria, and adherence., Methods: Using English primary care sentinel network data from 2014 to 2019, we assessed appropriate DOAC dose adjustment with creatinine clearance (CrCl). Our primary care sentinel cohort was a subset of 722 general practices, with 6.46 million currently registered patients at the time of this study., Results: Of 6 464 129 people in the cohort, 2.3% were aged ≥18 years with a diagnosis of AF, and 30.8% of these were prescribed vitamin K antagonist and 69.1% DOACs. Appropriate DOAC prescribing following CrCl measures improved between 2014 and 2019; dabigatran from 21.3% (95% CI 15.1% to 28.8%) to 48.7% (95% CI 45.0% to 52.4%); rivaroxaban from 22.1% (95% CI 16.7% to 28.4%) to 49.9% (95% CI 48.5% to 53.3%); edoxaban from 10.0% (95% CI 0.3% to 44.5%) in 2016 to 57.6% (95% CI 54.5% to 60.7%) in 2019; apixaban from 30.8% (95% CI 9.1% to 61.4%) in 2015 to 60.5% (95% CI 57.8% to 63.2%) in 2019.Adherence was highest for factor Xa inhibitors, increasing from 50.1% (95% CI 47.7% to 52.4%) in 2014 to 57.8% (95% CI 57.4% to 58.2%) in 2019. Asian and black/mixed ethnicity was associated with non-adherence (OR 1.81, 95% CI 1.56 to 2.09) as was male gender (OR 1.19, 95% CI 1.15 to 1.22), higher socioeconomic status (OR 1.60, 95% CI 1.52 to 1.68), being an ex-smoker (OR 1.12, 95% CI 1.06 to 1.19) and hypertension (OR 1.07, 95% CI 1.03 to 1.17)., Conclusions: The volume and quality of DOAC prescribing has increased yearly. Future interventions to augment quality of anticoagulant management should target disparities in adherence., Competing Interests: Competing interests: MJ, XF, JS, GD, FDRH and SdeL are employees of, and JW and MF honorary appointment at University of Oxford, which received funding from Bristol Myers Squibb and Pfizer to undertake this study. KGP, BS and JA are employees of Bristol Myers Squibb Pharmaceuticals. SE is a postgraduate doctoral student with SdeL at University of Surrey. SdeL is director of the Oxford Royal College of General Practitioners Research and Surveillance Centre and has also received funding through his university from Daiichi Sankyo for AF research. JS receives funding from the Wellcome Trust/Royal Society via a Sir Henry Dale Fellowship (ref: 211182/Z/18/Z) and an NIHR Oxford Biomedical Research Centre (BRC) Senior Fellowship. BCTF has acted as a consultant, speaker or received grants from Abbott Diabetes, AstraZeneca, Boehringer Ingelheim, Eli Lilly, GSK, Janssen, Medtronic, MSD, Napp, Novo Nordisk and Sanofi. This research was funded in part, by the Wellcome Trust (211182/Z/18/Z). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. FDRH acknowledges part support as director of the NIHR Applied Research Collaboration (ARC) Oxford Thames Valley, and Theme Lead of the NIHR OUH BRC. FDRH has also received occasional fees or expenses for speaking or consultancy from AZ, BI, Bayer, BMS/Pfizer and Novartis., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Physical exertion is a high-risk activity for aerosol emission of respiratory pathogens. We aimed to determine the safety and tolerability of healthy young adults wearing different types of face mask during moderate-to-high intensity exercise., Design: Cross-over randomised controlled study, completed between June 2021 and January 2022., Participants: Volunteers aged 18-35 years, who exercised regularly and had no significant pre-existing health conditions., Interventions: Comparison of wearing a surgical, cloth and filtering face piece (FFP3) mask to no mask during 4×15 min bouts of exercise. Exercise was running outdoors or indoor rowing at moderate-to-high intensity, with consistency of distance travelled between bouts confirmed using a smartphone application (Strava). Each participant completed each bout in random order., Outcomes: The primary outcome was change in oxygen saturations. Secondary outcomes were change in heart rate, perceived impact of face mask wearing during exercise and willingness to wear a face mask for future exercise., Results: All 72 volunteers (mean age 23.9) completed the study. Changes in oxygen saturations did not exceed the prespecified non-inferiority margin (2% difference) with any mask type compared with no mask. At the end of exercise, the estimated average difference in oxygen saturations for cloth mask was -0.07% (95% CI -0.39% to 0.25%), for surgical 0.28% (-0.04% to 0.60%) and for FFP3 -0.21% (-0.53% to 0.11%). The corresponding estimated average difference in heart rate for cloth mask was -1.20 bpm (95% CI -4.56 to 2.15), for surgical 0.36 bpm (95% CI -3.01 to 3.73) and for FFP3 0.52 bpm (95% CI -2.85 to 3.89). Wearing a face mask caused additional symptoms such as breathlessness (n=13, 18%) and dizziness (n=7, 10%). 33 participants broadly supported face mask wearing during exercise, particularly indoors, but 22 were opposed., Conclusion: This study adds to previous findings (mostly from non-randomised studies) that exercising at moderate-to-high intensity wearing a face mask appears to be safe in healthy, young adults., Trial Registration Number: NCT04932226., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

BackgroundPost-authorisation vaccine safety surveillance is well established for reporting common adverse events of interest (AEIs) following influenza vaccines, but not for COVID-19 vaccines.AimTo estimate the incidence of AEIs presenting to primary care following COVID-19 vaccination in England, and report safety profile differences between vaccine brands.MethodsWe used a self-controlled case series design to estimate relative incidence (RI) of AEIs reported to the national sentinel network, the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. We compared AEIs (overall and by clinical category) 7 days pre- and post-vaccination to background levels between 1 October 2020 and 12 September 2021.ResultsWithin 7,952,861 records, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs, 4.85% within 7 days post-vaccination. Overall, medically attended AEIs decreased post-vaccination against background levels. There was a 3-7% decrease in incidence within 7 days after both doses of Comirnaty (RI: 0.93; 95% CI: 0.91-0.94 and RI: 0.96; 95% CI: 0.94-0.98, respectively) and Vaxzevria (RI: 0.97; 95% CI: 0.95-0.98). A 20% increase was observed after one dose of Spikevax (RI: 1.20; 95% CI: 1.00-1.44). Fewer AEIs were reported as age increased. Types of AEIs, e.g. increased neurological and psychiatric conditions, varied between brands following two doses of Comirnaty (RI: 1.41; 95% CI: 1.28-1.56) and Vaxzevria (RI: 1.07; 95% CI: 0.97-1.78).ConclusionCOVID-19 vaccines are associated with a small decrease in medically attended AEI incidence. Sentinel networks could routinely report common AEI rates, contributing to reporting vaccine safety.

Background: Natriuretic peptide (NP) testing is recommended for patients presenting to primary care with symptoms of chronic heart failure (HF) to prioritise referral for diagnosis., Aim: To report NP test performance at European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guideline referral thresholds., Design and Setting: Diagnostic accuracy study using linked primary and secondary care data (2004 to 2018)., Method: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NP testing for HF diagnosis was assessed., Results: In total, 229 580 patients had an NP test and 21 102 (9.2%) were diagnosed with HF within 6 months. The ESC NT-proBNP threshold ≥125 pg/mL had a sensitivity of 94.6% (95% confidence interval [CI] = 94.2 to 95.0) and specificity of 50.0% (95% CI = 49.7 to 50.3), compared with sensitivity of 81.7% (95% CI = 81.0 to 82.3) and specificity of 80.3% (95% CI = 80.0 to 80.5) for the NICE NT-proBNP ≥400 pg/mL threshold. PPVs for an NT-proBNP test were 16.4% (95% CI = 16.1 to 16.6) and 30.0% (95% CI = 29.6 to 30.5) for ESC and NICE thresholds, respectively. For both guidelines, nearly all patients with an NT-proBNP level below the threshold did not have HF (NPV: ESC 98.9%, 95% CI = 98.8 to 99.0 and NICE 97.7%, 95% CI = 97.6 to 97.8)., Conclusion: At the higher NICE chronic HF guideline NP thresholds, one in five cases are initially missed in primary care but the lower ESC thresholds require more diagnostic assessments. NP is a reliable 'rule-out' test at both cut-points. The optimal NP threshold will depend on the priorities and capacity of the healthcare system., (© The Authors.)

Background: Around one million individuals in the UK have heart failure (HF), a chronic disease that causes significant morbidity and mortality. N-terminal pro-B-type natriuretic peptide (NT-proBNP) monitoring could help improve the care of patients with HF in the community., Aim: The aim of this study is to provide evidence to support the routine use of point-of-care (POC) NT-proBNP monitoring in primary care., Design & Setting: In this observational cohort study, the Roche Cobas h 232 POC device was used to measure NT-proBNP in 27 patients with HF at 0, 6, and 12 months, with a subset reanalysed in the laboratory for comparison., Method: Data were analysed for within-person and between-person variability and concordance with laboratory readings using Passing-Bablok regression. GPs reported whether POC results impacted clinical decisionmaking, and patients indicated their willingness to participate in long-term cohort studies using the Likert acceptability scale., Results: Within-person variability in POC NT-proBNP over 12 months was 881 pg/mL (95% confidence interval [CI] = 380 to 1382 pg/mL). Between-person variability was 1972 pg/mL (95% CI = 1,525 to 2791 pg/mL). Passing-Bablok regression showed no significant systematic difference between POC and laboratory measurements. Patients indicated a high level of acceptability, and GP decisionmaking was affected for at least one visit in a third of patients., Conclusion: Within-person variability in POC NT-proBNP is around half of between-person variability, so detecting changes could be of use in HF management. High patient acceptability and impact on clinical decisionmaking warrant further investigation in a larger long-term cohort study., (Copyright © 2022, The Authors.)

Introduction: Atrial fibrillation (AF) is a common arrhythmia associated with 30% of strokes, as well as other cardiovascular disease, dementia and death. AF meets many criteria for screening, but there is limited evidence that AF screening reduces stroke. Consequently, no countries recommend national screening programmes for AF. The Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) trial aims to determine whether screening for AF is effective at reducing risk of stroke. The aim of the pilot study is to assess feasibility of the main trial and inform implementation of screening and trial procedures., Methods and Analysis: SAFER is planned to be a pragmatic randomised controlled trial (RCT) of over 100 000 participants aged 70 years and over, not on long-term anticoagulation therapy at baseline, with an average follow-up of 5 years. Participants are asked to record four traces every day for 3 weeks on a hand-held single-lead ECG device. Cardiologists remotely confirm episodes of AF identified by the device algorithm, and general practitioners follow-up with anticoagulation as appropriate. The pilot study is a cluster RCT in 36 UK general practices, randomised 2:1 control to intervention, recruiting approximately 12 600 participants. Pilot study outcomes include AF detection rate, anticoagulation uptake and other parameters to incorporate into sample size calculations for the main trial. Questionnaires sent to a sample of participants will assess impact of screening on psychological health. Process evaluation and qualitative studies will underpin implementation of screening during the main trial. An economic evaluation using the pilot data will confirm whether it is plausible that screening might be cost-effective., Ethics and Dissemination: The London-Central Research Ethics Committee (19/LO/1597) and Confidentiality Advisory Group (19/CAG/0226) provided ethical approval. Dissemination will be via publications, patient-friendly summaries, reports and engagement with the UK National Screening Committee., Trial Registration Number: ISRCTN72104369., Competing Interests: Competing interests: JM has performed consultancy work for BMS/Pfizer and Omron. FDRH reports occasional consultancy for BMS/Pfizer, Bayer and BI over the past 5 years. NA is a member of the UK National Screening Committee’s Adult Reference Group. MS is a full-time employee of AstraZeneca. MRC reports consultancy for AstraZeneca, Abbott, Medtronic, Bayer, Novartis, Boehringer-Ingelheim-Lilly Alliance, Servier & Pfizer over the past 5 years. RMc’s employer the University of Oxford receives consultancy and licencing payments from Omron and Sensyne for BP telemonitoring interventions. GYHL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. No fees are received personally. SJG has received honoraria from Astra Zeneca for lectures at postgraduate educational meetings for primary care teams about type 2 diabetes. BF has received speaker fees, honoraria, and non-financial support from the BMS and Pfizer Alliance; grants to the Institution for investigator-initiated studies from the BMS and Pfizer Alliance; and loan devices for investigatorinitiated studies from Alivecor: all were unrelated to the present study but related to screening for AF., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Colchicine has been proposed as a COVID-19 treatment., Aim: To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community., Design and Setting: Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE)., Method: Adults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models., Results: The trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine ( n = 156), usual care ( n = 1145), and other treatments ( n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of -0.4% (95% CrI = -2.7 to 2.4)., Conclusion: Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community., (© The Authors.)

Objective: Heart failure (HF) is a malignant condition requiring urgent treatment. Guidelines recommend natriuretic peptide (NP) testing in primary care to prioritise referral for specialist diagnostic assessment. We aimed to assess association of baseline NP with hospitalisation and mortality in people with newly diagnosed HF., Methods: Population-based cohort study of 40 007 patients in the Clinical Practice Research Datalink in England with a new HF diagnosis (48% men, mean age 78.5 years). We used linked primary and secondary care data between 1 January 2004 and 31 December 2018 to report one-year hospitalisation and 1-year, 5-year and 10-year mortality by NP level., Results: 22 085 (55%) participants were hospitalised in the year following diagnosis. Adjusted odds of HF-related hospitalisation in those with a high NP (NT-proBNP >2000 pg/mL) were twofold greater (OR 2.26 95% CI 1.98 to 2.59) than a moderate NP (NT-proBNP 400-2000 pg/mL). All-cause mortality rates in the high NP group were 27%, 62% and 82% at 1, 5 and 10 years, compared with 19%, 50% and 77%, respectively, in the moderate NP group and, in a competing risks model, risk of HF-related death was 50% higher at each timepoint. Median time between NP test and HF diagnosis was 101 days (IQR 19-581)., Conclusions: High baseline NP is associated with increased HF-related hospitalisation and poor survival. While healthcare systems remain under pressure from the impact of COVID-19, research to test novel strategies to prevent hospitalisation and improve outcomes-such as a mandatory two-week HF diagnosis pathway-is urgently needed., Competing Interests: Competing interests: CJT reports personal fees from Vifor and Novartis outside the submitted work, and non-financial support from Roche outside the submitted work. FDRH reports personal fees and other from Novartis, personal fees and other from Boehringer Ingelheim and grants from Pfizer outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Decline in kidney function can result in adverse health outcomes. The Oxford Renal Cohort Study has detailed baseline assessments from 884 participants ≥60 years of age., Aim: To determine the proportion of participants with a 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., Method: 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/1.73 m 2 /year, improvement as eGFR increase >5 ml/min/1.73 m 2 /year, and remission in those with CKD at baseline and eGFR >60 ml/min/1.73 m 2 during follow-up. Cox proportional hazard models were used to identify factors associated with eGFR decline., Results: There was a net decline in eGFR in the 884 participants over 5 years of follow-up. In 686 participants with >2 eGFR tests 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., Conclusion: 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, although only a small proportion meet the National Institute for Health and Care Excellence criteria for referral to secondary care., (© The Authors.)

Background: The outcomes of patients newly diagnosed with atrial fibrillation (AF) following the introduction of direct-acting oral anticoagulants are not well known., Aim: To determine the 2-year outcomes of patients newly diagnosed with AF, and the effectiveness of oral anticoagulants in everyday practice., Design and Setting: This was a prospective observational cohort study in UK primary care., Method: In total, 3574 patients aged ≥18 years with a new AF diagnosis were enrolled. A propensity score was applied using an overlap weighting scheme to obtain unbiased estimates of the treatment effect of anticoagulation versus no anticoagulation on the occurrence of death, non-haemorrhagic stroke/systemic embolism, and major bleeding within 2 years of diagnosis., Results: Overall, 65.8% received anticoagulant therapy, 20.8% received an antiplatelet only, and 13.4% received neither. During the study period, the overall incidence rates of all-cause mortality, non-haemorrhagic stroke/systemic embolism, and major bleeding were 4.15 (95% confidence interval [CI] = 3.69 to 4.65), 1.45 (95% CI = 1.19 to 1.77), and 1.21 (95% CI = 0.97 to 1.50) per 100 person-years, respectively. Anticoagulation treatment compared with no anticoagulation treatment was associated with significantly lower all-cause mortality adjusted hazard ratio (aHR) 0.70 (95% CI = 0.53 to 0.93), significantly lower risk of non-haemorrhagic stroke/systemic embolism (aHR 0.39, 95% CI = 0.24 to 0.62), and a non-significant higher risk of major bleeding (aHR 1.31, 95% CI = 0.77 to 2.24)., Conclusion: The data support a benefit of anticoagulation in reducing stroke and death, without an increased risk of a major bleed in patients with new-onset AF. Anticoagulation treatment in patients at high risk of stroke who are not receiving anticoagulation may further improve outcomes., (© The Authors.)

Background: Many patients with heart failure with preserved ejection fraction (HFpEF) are undiagnosed, and UK general practice registers do not typically record heart failure (HF) subtype. Improvements in management of HFpEF is dependent on improved identification and characterisation of patients in primary care., Aim: To describe a cohort of patients recruited from primary care with suspected HFpEF and compare patients in whom HFpEF was confirmed and refuted., Design & Setting: Baseline data from a longitudinal cohort study of patients with suspected HFpEF recruited from primary care in two areas of England., Method: A screening algorithm and review were used to find patients on HF registers without a record of reduced ejection fraction (EF). Baseline evaluation included cardiac, mental and physical function, clinical characteristics, and patient reported outcomes. Confirmation of HFpEF was clinically adjudicated by a cardiologist., Results: In total, 93 (61%) of 152 patients were confirmed HFpEF. The mean age of patients with HFpEF was 79 years, 46% were female, 80% had hypertension, and 37% took ≥10 medications. Patients with HFpEF were more likely to be obese, pre-frail or frail, report more dyspnoea and fatigue, were more functionally impaired, and less active than patients in whom HFpEF was refuted. Few had attended cardiac rehabilitation., Conclusion: Patients with confirmed HFpEF had frequent multimorbidity, functional impairment, frailty, and polypharmacy. Although comorbid conditions were similar between people with and without HFpEF, the former had more obesity, symptoms, and worse physical function. These findings highlight the potential to optimise wellbeing through comorbidity management, medication rationalisation, rehabilitation, and supported self-management., (Copyright © 2021, The Authors.)

Background: The Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE) has provided in-pandemic evidence that azithromycin and doxycycline were not beneficial in the early primary care management of coronavirus 2019 disease (COVID-19)., Aim: To explore the extent of in-pandemic azithromycin and doxycycline use, and the scope for trial findings impacting on practice., Design & Setting: Crude rates of prescribing and respiratory tract infections (RTI) in 2020 were compared with 2019, using the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC)., Method: Negative binomial models were used to compare azithromycin and doxycycline prescribing, 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)., Results: Azithromycin prescriptions increased 7% in 2020 compared with 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 from 0.51% in 2019 to 0.72% in 2020 (risk difference 0.214%; 95% CI = 0.211 to 0.217); doxycycline rose from 11.86% in 2019 to 15.79% in 2020 (risk difference 3.93%; 95% CI = 3.73 to 4.14). The adjusted IRR showed azithromycin prescribing was 22% higher in 2020 (IRR = 1.22; 95% CI = 1.19 to 1.26; P <0.0001). For every unit rise in confirmed COVID-19 there was an associated 3% rise in prescription (IRR = 1.03; 95% CI = 1.02 to 1.03; P <0.0001); whereas these measures were static for doxycycline., Conclusion: PRINCIPLE demonstrates scope for improved antimicrobial stewardship during a pandemic., (Copyright © 2021, The Authors.)

Objective: To assess current management practice of heart failure with reduced ejection fraction (HFrEF) in multinational primary care (PC) and determine whether N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP)-guided referral of HFrEF patients from PC to a cardiologist could improve care, defined as adherence to European Society of Cardiology (ESC) guideline-recommended pharmacotherapy., Methods: PRospective Evaluation of natriuretic peptide-based reFERral of patients with chronic HF in PC (PREFER) study enrolled HFrEF patients from PC considered clinically stable and those with NT-pro-BNP ≥600 pg/mL were referred to a cardiologist for optimisation of HF treatment. The primary outcome of adherence to ESC HF guidelines after referral to specialist was assessed at the second visit within 4 weeks of cardiologist's referral and no later than 6 months after the baseline visit. Based on futility interim analysis, the study was terminated early., Results: In total, 1415 HFrEF patients from 223 PCs from 18 countries in Europe were enrolled. Of these, 1324 (96.9%) were considered clinically stable and 920 (65.0%) had NT-pro-BNP ≥600 pg/mL (mean: 2631 pg/mL). In total, 861 (60.8%) patients fulfilled both criteria and were referred to a cardiologist. Before cardiologist consultation, 10.1% of patients were on ESC guideline-recommended HFrEF medications and 2.7% were on recommended dosages of HFrEF medication (defined as ≥50% of ESC guideline-recommended dose). Postreferral, prescribed HFrEF drugs remained largely unchanged except for an increase in diuretics (+4.6%) and mineralocorticoid receptor antagonists (+7.9%). No significant increase in patients' adherence to guideline-defined drug combinations (11.2% post-referral vs 10.1% baseline) or drug combinations and dosages (3.3% postreferral vs 2.7% baseline) was observed after cardiologist consultation., Conclusions: PREFER demonstrates substantial suboptimal treatment of HFrEF patients in the real world. Referral of patients with elevated NT-pro-BNP levels from PC to cardiologist did not result in meaningful treatment optimisation for treatments with known mortality and morbidity benefit., Competing Interests: Competing interests: RH acknowledges his part-funding from the National Institute for Health Research (NIHR) School for Primary Care Research, the NIHR Collaboration for Leadership in Health Research and Care (CLARHC) Oxford, the NIHR Oxford Biomedical Research Centre (BRC, UHT), and the NIHR Oxford Medtech and In-Vitro Diagnostics Co-operative (MIC) and has received occasional fees for consulting or speaking from companies including Novartis. RH and PF are employees of Novartis. HB receives research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021 & PI17/01799), Astra-Zeneca, BMS, Janssen and Novartis and has received consulting fees from Astra-Zeneca, Bayer, BMS-Pfizer, Novartis; and speaking fees or support for attending scientific meetings from Astra-Zeneca, Bayer, BMS-Pfizer, Novartis, and MEDSCAPE-the heart.og. YMP received consultancy fees from Novartis, Roche Diagnostics and holds minority shares in a University spin-off. FG has received fees for consulting and speaking honoraria from Novartis, Carmat, Orion and fees for consulting, speaking and as an investigator from Abbott. He has also received research grant from Orion and speaking honoraria from Boehringer-Ingelheim and received fees for consulting from Bayer and Pfizer. MO has been contracted by Novartis., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Monitoring is the mainstay of chronic kidney disease management in primary care; however, there is little evidence about the best way to do this., Aim: To compare the effectiveness of estimated glomerular filtration rate (eGFR) derived from serum creatinine and serum cystatin C to predict renal function decline among those with a recent eGFR of 30-89 ml/min/1.73 m 2 ., Design and Setting: Observational cohort study in UK primary care., Method: Serum creatinine and serum cystatin C were both measured at seven study visits over 2 years in 750 patients aged ≥18 years with an eGFR of 30-89 ml/min/1.73 m 2 within the previous year. The primary outcome was change in eGFR derived from serum creatinine or serum cystatin C between 6 and 24 months., Results: Average change in eGFR was 0.51 ml/min/1.73 m 2 /year when estimated by serum creatinine and -2.35 ml/min/1.73 m 2 /year when estimated by serum cystatin C. The c-statistic for predicting renal decline using serum creatininederived eGFR was 0.495 (95% confidence interval [CI] = 0.471 to 0.519). The equivalent c-statistic using serum cystatin C-derived eGFR was 0.497 (95% CI = 0.468 to 0.525). Similar results were obtained when restricting analyses to those aged ≥75 or <75 years, or with eGFR ≥60 ml/min/1.73 m 2 . In those with eGFR <60 ml/min/1.73 m 2 , serum cystatin C-derived eGFR was more predictive than serum creatinine-derived eGFR for future decline in kidney function., Conclusion: In the primary analysis neither eGFR estimated from serum creatinine nor from serum cystatin C predicted future change in kidney function, partly due to small changes during 2 years. In some secondary analyses there was a suggestion that serum cystatin C was a more useful biomarker to estimate eGFR, especially in those with a baseline eGFR <60 ml/min/1.73 m 2 ., (© The Authors.)

Objective: Valvular heart disease (VHD) is present in half the population aged >65 years but is usually mild and of uncertain importance. We investigated the association between VHD and its phenotypes with all-cause and cause-specific mortality., Methods: The OxVALVE (Oxford Valvular Heart Disease) population cohort study screened 4009 participants aged >65 years to establish the presence and severity of VHD. We linked data to a national mortality registry and undertook detailed outcome analysis., Results: Mortality data were available for 3511 participants, of whom 361 (10.3%) died (median 6.49 years follow-up). Most had some form of valve abnormality (n=2645, 70.2%). In adjusted analyses, neither mild VHD (prevalence 44.9%) nor clinically significant VHD (moderate or severe stenosis or regurgitation; 5.2%) was associated with increased all-cause mortality (HR 1.20, 95% CI 0.96 to 1.51 and HR 1.47, 95% CI 0.94 to 2.31, respectively). Conversely, advanced aortic sclerosis (prevalence 2.25%) and advanced mitral annular calcification (MAC, 1.31%) were associated with an increased risk of death (HR 2.05, 95% CI 1.28 to 3.30 and HR 2.51, 95% CI 1.41 to 4.49, respectively). Mortality was highest for people with both clinically significant VHD and advanced aortic sclerosis or MAC (HR 4.38, 95% CI 1.99 to 9.67)., Conclusions: Advanced aortic sclerosis or MAC is associated with a worse outcome, particularly for patients with significant VHD, but also in the absence of other VHD. Older patients with mild VHD can be reassured about their prognosis. The absence of an association between significant VHD and mortality may reflect its relatively low prevalence in our cohort., Competing Interests: Competing interests: CJT is an NIHR academic clinical lecturer and reports personal fees from Vifor and Novartis, and non-financial support from Roche, outside the submitted work. AKR and JMO-M are supported by the NIHR BRC Oxford University Hospitals NHS Foundation Trust. NRJ is a Wellcome Trust doctoral research fellow (grant number 203921/Z/16/Z). FDRH acknowledges support from the NIHR School for Primary Care Research, NIHR ARC Oxford Thames Valley and the NIHR OUH BRC., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Patients with myeloma experience substantial delays in their diagnosis, which can adversely affect their prognosis., Aim: To generate a clinical prediction rule to identify primary care patients who are at highest risk of myeloma., Design and Setting: Retrospective open cohort study using electronic health records data from the UK's Clinical Practice Research Datalink (CPRD) between 1 January 2000 and 1 January 2014., Method: Patients from the CPRD were included in the study if they were aged ≥40 years, had two full blood counts within a year, and had no previous diagnosis of myeloma. Cases of myeloma were identified in the following 2 years. Derivation and external validation datasets were created based on geographical region. Prediction equations were estimated using Cox proportional hazards models including patient characteristics, symptoms, and blood test results. Calibration, discrimination, and clinical utility were evaluated in the validation set., Results: Of 1 281 926 eligible patients, 737 (0.06%) were diagnosed with myeloma within 2 years. Independent predictors of myeloma included: older age; male sex; back, chest and rib pain; nosebleeds; low haemoglobin, platelets, and white cell count; and raised mean corpuscular volume, calcium, and erythrocyte sedimentation rate. A model including symptoms and full blood count had an area under the curve of 0.84 (95% CI = 0.81 to 0.87) and sensitivity of 62% (95% CI = 55% to 68%) at the highest risk decile. The corresponding statistics for a second model, which also included calcium and inflammatory markers, were an area under the curve of 0.87 (95% CI = 0.84 to 0.90) and sensitivity of 72% (95% CI = 66% to 78%)., Conclusion: The implementation of these prediction rules would highlight the possibility of myeloma in patients where GPs do not suspect myeloma. Future research should focus on the prospective evaluation of further external validity and the impact on clinical practice., (© The Authors.)

Background: The SARS-CoV-2 pandemic has passed its first peak in Europe., Aim: To describe the mortality in England and its association with SARS-CoV-2 status and other demographic and risk factors., Design and Setting: Cross-sectional analyses of people with known SARS-CoV-2 status in the Oxford RCGP Research and Surveillance Centre (RSC) sentinel network., Method: Pseudonymised, coded clinical data were uploaded from volunteer general practice members of this nationally representative network ( n = 4 413 734). All-cause mortality was compared with national rates for 2019, using a relative survival model, reporting relative hazard ratios (RHR), and 95% confidence intervals (CI). A multivariable adjusted odds ratios (OR) analysis was conducted for those with known SARS-CoV-2 status ( n = 56 628, 1.3%) including multiple imputation and inverse probability analysis, and a complete cases sensitivity analysis., Results: Mortality peaked in week 16. People living in households of ≥9 had a fivefold increase in relative mortality (RHR = 5.1, 95% CI = 4.87 to 5.31, P <0.0001). The ORs of mortality were 8.9 (95% CI = 6.7 to 11.8, P <0.0001) and 9.7 (95% CI = 7.1 to 13.2, P <0.0001) for virologically and clinically diagnosed cases respectively, using people with negative tests as reference. The adjusted mortality for the virologically confirmed group was 18.1% (95% CI = 17.6 to 18.7). Male sex, population density, black ethnicity (compared to white), and people with long-term conditions, including learning disability (OR = 1.96, 95% CI = 1.22 to 3.18, P = 0.0056) had higher odds of mortality., Conclusion: The first SARS-CoV-2 peak in England has been associated with excess mortality. Planning for subsequent peaks needs to better manage risk in males, those of black ethnicity, older people, people with learning disabilities, and people who live in multi-occupancy dwellings., (©The Authors.)

Competing Interests: Declaration Competing Interest None.

Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in a rapid change in workload across healthcare systems. Factors related to this adaptation in UK primary care have not yet been examined., Aim: To assess the responsiveness and prioritisation of primary care consultation type for older adults during the COVID-19 pandemic., Design and Setting: A cross-sectional database study examining consultations between 17 February and 10 May 2020 for patients aged ≥65 years, drawn from primary care practices within the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network, UK., Method: The authors reported the proportion of consultation type across five categories: clinical administration, electronic/video, face-to-face, telephone, and home visits. Temporal trends in telephone and face-to-face consultations were analysed by polypharmacy, frailty status, and socioeconomic group using incidence rate ratios (IRR)., Results: Across 3 851 304 consultations, the population median age was 75 years (interquartile range [IQR] 70-82); and 46% ( n = 82 926) of the cohort ( N = 180 420) were male. The rate of telephone and electronic/video consultations more than doubled across the study period (106.0% and 102.8%, respectively). Face-to-face consultations fell by 64.6% and home visits by 62.6%. This predominantly occurred across week 11 (week commencing 9 March 2020), coinciding with national policy change. Polypharmacy and frailty were associated with a relative increase in consultations. The greatest relative increase was among people taking ≥10 medications compared with those taking none (face-to-face IRR 9.90, 95% CI = 9.55 to 10.26; telephone IRR 17.64, 95% CI = 16.89 to 18.41)., Conclusion: Primary care has undergone an unprecedented in-pandemic reorganisation while retaining focus on patients with increased complexity., (©The Authors.)

Background: Home blood-pressure (BP) monitoring is recommended in guidelines and is increasingly popular with patients and health professionals, but the accuracy of patients' own monitors in real-world use is not known., Aim: To assess the accuracy of home BP monitors used by people with hypertension, and to investigate factors affecting accuracy., Design and Setting: Cross-sectional, observational study in urban and suburban settings in central England., Method: Patients ( n = 6891) on the hypertension register at seven practices in the West Midlands, England, were surveyed to ascertain whether they owned a BP monitor and wanted it tested. Monitor accuracy was compared with a calibrated reference device at 50 mmHg intervals between 0-280/300 mmHg (static pressure test); a difference from the reference monitor of +/-3 mmHg at any interval was considered a failure. Cuff performance was also assessed. Results were analysed by frequency of use, length of time in service, make and model, monitor validation status, purchase price, and any previous testing., Results: In total, 251 (76%, 95% confidence interval [95% CI] = 71 to 80%) of 331 tested devices passed all tests (monitors and cuffs), and 86% (CI] = 82 to 90%) passed the static pressure test; deficiencies were, primarily, because of monitors overestimating BP. A total of 40% of testable monitors were not validated. The pass rate on the static pressure test was greater in validated monitors (96%, 95% CI = 94 to 98%) versus unvalidated monitors (64%, 95% CI = 58 to 69%), those retailing for >£10 (90%, 95% CI = 86 to 94%), those retailing for ≤£10 (66%, 95% CI = 51 to 80%), those in use for ≤4 years (95%, 95% CI = 91 to 98%), and those in use for >4 years (74%, 95% CI = 67 to 82%). All in all, 12% of cuffs failed., Conclusion: Patients' own BP monitor failure rate was similar to that demonstrated in studies performed in professional settings, although cuff failure was more frequent. Clinicians can be confident of the accuracy of patients' own BP monitors if the devices are validated and ≤4 years old., (©The Authors.)

Background: Chronic kidney disease (CKD) is a largely asymptomatic condition of diminished renal function, which may not be detected until advanced stages without screening., Aim: To establish undiagnosed and overall CKD prevalence using a cross-sectional analysis., Design and Setting: Longitudinal cohort study in UK primary care., Method: Participants aged ≥60 years were invited to attend CKD screening visits to determine whether they had reduced renal function (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m 2 or albumin:creatinine ratio ≥3 mg/mmol). Those with existing CKD, low eGFR, evidence of albuminuria, or two positive screening tests attended a baseline assessment (CKD cohort)., Results: A total of 3207 participants were recruited and 861 attended the baseline assessment. The CKD cohort consisted of 327 people with existing CKD, 257 people with CKD diagnosed through screening (CKD prevalence of 18.2%, 95% confidence interval [CI] = 16.9 to 19.6), and 277 with borderline/transient decreased renal function. In the CKD cohort, 54.4% were female, mean standard deviation (SD) age was 74.0 (SD 6.9) years, and mean eGFR was 58.0 (SD 18.4) ml/min/1.73 m 2 . Of the 584 with confirmed CKD, 44.0% were diagnosed through screening. Over half of the CKD cohort (51.9%, 447/861) fell into CKD stages 3-5 at their baseline assessment, giving an overall prevalence of CKD stages 3-5 of 13.9% (95% CI = 12.8 to 15.1). More people had reduced eGFR using the Modification of Diet in Renal Disease (MDRD) equation than with CKD Epidemiology Collaboration (CKD-EPI) equation in the 60-75-year age group and more had reduced eGFR using CKD-EPI in the ≥80-year age group., Conclusion: This study found that around 44.0% of people living with CKD are undiagnosed without screening, and prevalence of CKD stages 1-5 was 18.2% in participants aged >60 years. Follow-up will provide data on annual incidence, rate of CKD progression, determinants of rapid progression, and predictors of cardiovascular events., (©The Authors.)

Background: Subclinical thyroid dysfunction - abnormal serum thyrotrophin (thyroid-stimulating hormone; TSH) concentrations with normal free thyroxine (FT4) is common in older people. It remains unclear whether individuals with subclinical serum status experience an increased symptom profile., Aim: To compare the prevalence of those symptoms typically associated with overt thyroid dysfunction in older individuals with a subclinical and euthyroid serum profile., Design and Setting: Cross-sectional study, nested within the Birmingham Elderly Thyroid Study (BETS); from 19 UK general practices., Method: Adults living in a community setting (aged ≥65 years), without overt thyroid dysfunction or associated treatment, self-reported the presence or absence of 18 symptoms (while serum result naïve). Serum concentrations of TSH and FT4 were measured to establish thyroid status., Results: A total of 2870 individuals were screened: 2703 (94%) were categorised as euthyroid (normal), 29 (1%) subclinically hyperthyroid, and 138 (5%) subclinically hypothyroid. Symptoms were common in all groups. No significant differences in the prevalence of individual symptoms were observed between the euthyroid and subclinically hypothyroid groups nor in comparison with the subclinically hyperthyroid group. Multivariate logistic regression analysis failed to reveal an association between individual or multiple symptoms and subclinical status., Conclusion: Findings suggest that subclinical thyroid dysfunction does not confer a symptom burden in older individuals and support adherence to guidelines in the non-treatment of subclinical thyroid dysfunction. GPs may use the findings to reassure older people presenting with symptoms that subclinical thyroid dysfunction is an unlikely explanation. The presence of persistently abnormal TSH concentrations may be linked to long-term risks of cardiovascular disease, especially atrial fibrillation, but whether this should prompt treatment and whether such treatment alters vascular outcomes is unknown., (© British Journal of General Practice 2020.)

Background: Heart failure with preserved ejection fraction (HFpEF) is less well understood than heart failure with reduced ejection fraction (HFrEF), with greater diagnostic difficulty and management uncertainty., Aim: The primary aim is to develop an optimised programme that is informed by the needs and experiences of people with HFpEF and healthcare providers. This article presents the rationale and protocol for the Optimising Management of Patients with Heart Failure with Preserved Ejection Fraction in Primary Care (OPTIMISE-HFpEF) research programme., Design & Setting: This is a multi-method programme of research conducted in the UK., Method: OPTIMISE-HFpEF is a multi-site programme of research with three distinct work packages (WPs). WP1 is a systematic review of heart failure disease management programmes (HF-DMPs) tested in patients with HFpEF. WP2 has three components (a, b, c) that enable the characteristics, needs, and experiences of people with HFpEF, their carers, and healthcare providers to be understood. Qualitative enquiry (WP2a) with patients and providers will be conducted in three UK sites exploring patient and provider perspectives, with an additional qualitative component (WP2c) in one site to focus on transitions in care and carer perspectives. A longitudinal cohort study (WP2b), recruiting from four UK sites, will allow patients to be characterised and their illness trajectory observed across 1 year of follow-up. Finally, WP3 will synthesise the findings and conduct work to gain consensus on how best to identify and manage this patient group., Results: Results from the four work packages will be synthesised to produce a summary of key learning points and possible solutions (optimised programme) which will be presented to a broad spectrum of stakeholders to gain consensus on a way forward., Conclusion: HFpEF is often described as the greatest unmet need in cardiology. The OPTIMISE-HFpEF programme aims to address this need in primary care, which is arguably the most appropriate setting for managing HFpEF., (Copyright © 2019, The Authors.)

Background: The obesity epidemic has major public health consequences. Expert dietetic and behavioural counselling with intensive follow-up is effective, but resource requirements severely restrict widespread implementation in primary care, where most patients are managed. We aimed to estimate the effectiveness and cost-effectiveness of an internet-based behavioural intervention (POWeR+) combined with brief practice nurse support in primary care., Methods: We did this pragmatic, parallel-group, randomised controlled trial at 56 primary care practices in central and south England. Eligible adults aged 18 years or older with a BMI of 30 kg/m(2) or more (or ≥28 kg/m(2) with hypertension, hypercholesterolaemia, or diabetes) registered online with POWeR+-a 24 session, web-based, weight management intervention lasting 6 months. After registration, the website automatically randomly assigned patients (1:1:1), via computer-generated random numbers, to receive evidence-based dietetic advice to swap foods for similar, but healthier, choices and increase fruit and vegetable intake, in addition to 6 monthly nurse follow-up (control group); web-based intervention and face-to-face nurse support (POWeR+Face-to-face [POWeR+F]; up to seven nurse contacts over 6 months); or web-based intervention and remote nurse support (POWeR+Remote [POWeR+R]; up to five emails or brief phone calls over 6 months). Participants and investigators were masked to group allocation at the point of randomisation; masking of participants was not possible after randomisation. The primary outcome was weight loss averaged over 12 months. We did a secondary analysis of weight to measure maintenance of 5% weight loss at months 6 and 12. We modelled the cost-effectiveness of each intervention. We did analysis by intention to treat, with multiple imputation for missing data. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN21244703., Findings: Between Jan 30, 2013, and March 20, 2014, 818 participants were randomly assigned to the control group (n=279), the POWeR+F group (n=269), or the POWeR+R group (n=270). Weight loss averaged over 12 months was recorded in 666 (81%) participants. The control group lost almost 3 kg over 12 months (crude mean weight: baseline 104·38 kg [SD 21·11; n=279], 6 months 101·91 kg [19·35; n=136], 12 months 101·74 kg [19·57; n=227]). The primary imputed analysis showed that compared with the control group, patients in the POWeR+F group achieved an additional weight reduction of 1·5 kg (95% CI 0·6-2·4; p=0·001) averaged over 12 months, and patients in the POWeR+R group achieved an additional 1·3 kg (0·34-2·2; p=0·007). 21% of patients in the control group had maintained a clinically important 5% weight reduction at month 12, compared with 29% of patients in the POWeR+F group (risk ratio 1·56, 0·96-2·51; p=0·070) and 32% of patients in the POWeR+R group (1·82, 1·31-2·74; p=0·004). The incremental overall cost to the health service per kg weight lost with the POWeR+ interventions versus the control strategy was £18 (95% CI -129 to 195) for POWeR+F and -£25 (-268 to 157) for POWeR+R; the probability of being cost-effective at a threshold of £100 per kg lost was 88% and 98%, respectively. No adverse events were reported., Interpretation: Weight loss can be maintained in some individuals by use of novel written material with occasional brief nurse follow-up. However, more people can maintain clinically important weight reductions with a web-based behavioural program and brief remote follow-up, with no increase in health service costs. Future research should assess the extent to which clinically important weight loss can be maintained beyond 1 year., Funding: Health Technology Assessment Programme of the National Institute for Health Research., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)