Primary Care Practices In England Research Articles

Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality

The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear. To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening. This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021. Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation). The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis. Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P = .03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P < .001) and localized (T1/T2: 3.6% vs 3.1%; P < .001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P = .11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment. In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small. isrctn.org Identifier: ISRCTN92187251.

Implementing Germ Defence digital behaviour change intervention via all primary care practices in England to reduce respiratory infections during the COVID-19 pandemic: an efficient cluster randomised controlled trial using the OpenSAFELY platform

BackgroundGerm Defence (www.germdefence.org) is an evidence-based interactive website that promotes behaviour change for infection control within households. To maximise the potential of Germ Defence to effectively reduce the spread of COVID-19, the intervention needed to be implemented at scale rapidly.MethodsWith NHS England approval, we conducted an efficient two-arm (1:1 ratio) cluster randomised controlled trial (RCT) to examine the effectiveness of randomising implementation of Germ Defence via general practitioner (GP) practices across England, UK, compared with usual care to disseminate Germ Defence to patients. GP practices randomised to the intervention arm (n = 3292) were emailed and asked to disseminate Germ Defence to all adult patients via mobile phone text, email or social media. Usual care arm GP practices (n = 3287) maintained standard management for the 4-month trial period and then asked to share Germ Defence with their adult patients. The primary outcome was the rate of GP presentations for respiratory tract infections (RTI) per patient. Secondary outcomes comprised rates of acute RTIs, confirmed COVID-19 diagnoses and suspected COVID-19 diagnoses, COVID-19 symptoms, gastrointestinal infection diagnoses, antibiotic usage and hospital admissions. The impact of the intervention on outcome rates was assessed using negative binomial regression modelling within the OpenSAFELY platform. The uptake of the intervention by GP practice and by patients was measured via website analytics.ResultsGerm Defence was used 310,731 times. The average website satisfaction score was 7.52 (0–10 not at all to very satisfied, N = 9933). There was no evidence of a difference in the rate of RTIs between intervention and control practices (rate ratio (RR) 1.01, 95% CI 0.96, 1.06, p = 0.70). This was similar to all other eight health outcomes. Patient engagement within intervention arm practices ranged from 0 to 48% of a practice list.ConclusionsWhile the RCT did not demonstrate a difference in health outcomes, we demonstrated that rapid large-scale implementation of a digital behavioural intervention is possible and can be evaluated with a novel efficient prospective RCT methodology analysing routinely collected patient data entirely within a trusted research environment.Trial registrationThis trial was registered in the ISRCTN registry (14602359) on 12 August 2020.

Effectiveness and cost-effectiveness of offering a chair-based yoga programme in addition to usual care in older adults with multiple long-term conditions: a pragmatic, parallel group, open label, randomised controlled trial

Background People with multiple long-term conditions are more likely to have poorer health-related quality of life (HRQOL). Yoga has the potential to improve HRQOL. Gentle Years Yoga© (GYY) is a chair-based yoga programme for older adults. We investigated the effectiveness and cost-effectiveness of the GYY programme in older adults with multiple long-term conditions. Methods In this pragmatic, multi-site, open, randomised controlled trial, we recruited older adults aged ≥65 years with ≥2 long-term conditions from 15 primary care practices in England and Wales. Participants were randomly assigned to usual care control or a 12-week, group-based, GYY programme delivered face-to-face or online by qualified yoga teachers. The primary outcome was HRQOL (assessed with EQ-5D-5L) over 12 months. Secondary outcomes included anxiety, depression, falls, loneliness, healthcare resource use, and adverse events. Results Between October 2019 and October 2021, 454 participants were randomly assigned to the intervention (n=240) and control (n=214) groups. Seven GYY courses were delivered face-to-face and 12 courses were delivered online. The mean number of classes attended among all intervention participants was nine (SD 4, median 10). In our intention-to-treat analysis (n=422), there was no statistically significant difference between trial groups in the primary outcome of HRQOL (adjusted difference in mean EQ-5D-5L = 0.020 [favouring intervention]; 95% CI -0.006 to 0.045, p=0.14). There were also no statistically significant differences in key secondary outcomes. No serious, related adverse events were reported. The incremental cost-effectiveness ratio was £4,546 per quality-adjusted life-year (QALY) and the intervention had a 79% probability of being cost-effective at a willingness-to-pay threshold of £20,000 per QALY. Conclusions The offer of a 12-week chair-based yoga programme in addition to usual care did not improve HRQOL in older adults with multiple long-term conditions. However, the intervention was safe, acceptable, and probably cost-effective.

Understanding Measurement of postural hypotension: a nationwide survey of primary care practice in England.

Postural hypotension (PH), the drop in blood pressure (BP) on standing, is associated with falls, all-cause mortality and cognitive decline. PH diagnostic criteria require lying-to-standing BP measurements. PH Prevalence in older adults is 20%, however, it is infrequently recorded in primary care records, suggesting PH testing and/or recording is under-utilised in this setting. To understand current PH measurement and management by primary care practitioners in England. Clinical Research Networks circulated an online survey to primary care clinicians involved in measurement of BP. Demographics and responses were summarised as percentages, or median and inter-quartile ranges (IQR), as appropriate. The survey remains open until 30 November 2022; full results will be presented at the conference. To date, there are 669 replies (341 doctors, 179 nurses, 70 healthcare assistants, 23 pharmacists, 56 other roles); median age 45 (IQR 38 to 53), 72% female. Overall, 597 (89%) responders check for PH, predominantly when symptoms are present (98%). Less common reasons to check include patients being over 80 (24%), Parkinson's disease (21%), hypertension reviews (18%), medication reviews (12%) or diabetes reviews (11%). Sitting-to-standing BP measurements are common (77%); only 22% use lying-to-standing. Only 64% ensure a rest period before sitting or lying BP measurement and only 1 (IQR 1 to 2) standing BP measurement is made, usually (66%) within the first minute of standing. Interim findings suggest that most PH assessments in primary care do not meet current guideline criteria. Full findings from this survey are expected to inform and influence future national guidelines.

Influences on Patient Uptake of and Engagement With the National Health Service Digital Diabetes Prevention Programme: Qualitative Interview Study

Digital diabetes prevention programs (digital-DPPs) are being implemented as population-based approaches to type 2 diabetes mellitus prevention in several countries to address problems with the uptake of traditional face-to-face diabetes prevention programs. However, assessments of digital-DPPs have largely focused on clinical outcomes and usability among those who have taken them up, whereas crucial information on decision-making about uptake (eg, whether a user downloads and registers on an app) and engagement (eg, the extent of use of an app or its components over time) is limited. Greater understanding of factors that influence uptake and engagement decisions may support large-scale deployments of digital-DPPs in real-world settings. This study aimed to explore the key influences on uptake and engagement decisions of individuals who were offered the National Health Service Healthier You: Digital Diabetes Prevention Programme (NHS-digital-DPP). A qualitative interview study was conducted using semistructured interviews. Participants were adults, aged ≥18 years, diagnosed with nondiabetic hyperglycemia, and those who had been offered the NHS-digital-DPP. Recruitment was conducted via 4 providers of the NHS-digital-DPP and 3 primary care practices in England. Interviews were conducted remotely and were guided by a theoretically informed topic guide. Analysis of interviews was conducted using an inductive thematic analysis approach. Interviews were conducted with 32 participants who had either accepted or declined the NHS-digital-DPP. In total, 7 overarching themes were identified as important factors in both decisions to take up and to engage with the NHS-digital-DPP. These were knowledge and understanding, referral process, self-efficacy, self-identity, motivation and support, advantages of digital service, and reflexive monitoring. Perceptions of accessibility and convenience of the NHS-digital-DPP were particularly important for uptake, and barriers in terms of the referral process and health care professionals' engagement were reported. Specific digital features including health coaches and monitoring tools were important for engagement. This study adds to the literature on factors that influence the uptake of and engagement with digital-DPPs and suggests that digital-DPPs can overcome many barriers to the uptake of face-to-face diabetes prevention programs in supporting lifestyle changes aimed at diabetes prevention.

Mental Health Morbidities and Time to Cancer Diagnosis Among Adults With Colon Cancer in England

Mental health morbidity (MHM) in patients presenting with possible cancer symptoms may be associated with prediagnostic care and time to cancer diagnosis. To compare the length of intervals to cancer diagnosis by preexisting MHM status in patients who presented with symptoms of as-yet-undiagnosed colon cancer and evaluate their risk of emergency cancer diagnosis. This cohort study was conducted using linked primary care data obtained from the population-based Clinical Practice Research Datalink, which includes primary care practices in England, linked to cancer registry and hospital data. Included participants were 3766 patients diagnosed with colon cancer between 2011 and 2015 presenting with cancer-relevant symptoms up to 24 months before their diagnosis. Data analysis was performed in January 2021 to April 2022. Mental health conditions recorded in primary care before cancer diagnosis, including anxiety, depression, schizophrenia, bipolar disorder, alcohol addiction, anorexia, and bulimia. Fast-track (also termed 2-week wait) specialist referral for investigations, time to colonoscopy and cancer diagnosis, and risk of emergency cancer diagnosis. Among 3766 patients with colon cancer (median [IQR] age, 75 [65-82] years; 1911 [50.7%] women ), 623 patients [16.5%] had preexisting MHM recorded in primary care the year before cancer diagnosis, including 562 patients (14.9%) with preexisting anxiety or depression (accounting for 90.2% of patients with preexisting MHM) and 61 patients (1.6%) with other MHM; 3143 patients (83.5%) did not have MHM. Patients with MHM had records of red-flag symptoms or signs (ie, rectal bleeding, change in bowel habit, or anemia) in the 24 months before cancer diagnosis in a smaller proportion compared with patients without MHM (308 patients [49.4%] vs 1807 patients [57.5%]; P < .001). Even when red-flag symptoms were recorded, patients with MHM had lower odds of fast-track specialist referral (adjusted odds ratio [OR] = 0.72; 95% CI, 0.55-0.94; P = .01). Among 2115 patients with red-flag symptoms or signs, 308 patients with MHM experienced a more than 2-fold longer median (IQR) time to cancer diagnosis (326 [75-552] days vs 133 [47-422] days) and higher odds of emergency diagnosis (90 patients [29.2%] vs 327 patients [18.1%]; adjusted OR = 1.63; 95% CI, 1.23-2.24; P < .001) compared with 1807 patients without MHM. This study found that patients with MHM experienced large and prognostically consequential disparities in diagnostic care before a colon cancer diagnosis. These findings suggest that appropriate pathways and follow-up strategies after symptomatic presentation are needed for earlier cancer diagnoses and improved health outcomes in this large patient group.

BMI and HbA1c are metabolic markers for pancreatic cancer: Matched case-control study using a UK primary care database.

BackgroundWeight loss, hyperglycaemia and diabetes are known features of pancreatic cancer. We quantified the timing and the amount of changes in body mass index (BMI) and glycated haemoglobin (HbA1c), and their association with pancreatic cancer from five years before diagnosis.MethodsA matched case-control study was undertaken within 590 primary care practices in England, United Kingdom. 8,777 patients diagnosed with pancreatic cancer (cases) between 1st January 2007 and 31st August 2020 were matched to 34,979 controls by age, gender and diabetes. Longitudinal trends in BMI and HbA1c were visualised. Odds ratios adjusted for demographic and lifestyle factors (aOR) and 95% confidence intervals (CI) were calculated with conditional logistic regression. Subgroup analyses were undertaken according to the diabetes status.ResultsChanges in BMI and HbA1c observed for cases on longitudinal plots started one and two years (respectively) before diagnosis. In the year before diagnosis, a 1 kg/m2 decrease in BMI between cases and controls was associated with aOR for pancreatic cancer of 1.05 (95% CI 1.05 to 1.06), and a 1 mmol/mol increase in HbA1c was associated with aOR of 1.06 (1.06 to 1.07). ORs remained statistically significant (p < 0.001) for 2 years before pancreatic cancer diagnosis for BMI and 3 years for HbA1c. Subgroup analysis revealed that the decrease in BMI was associated with a higher pancreatic cancer risk for people with diabetes than for people without (aORs 1.08, 1.06 to 1.09 versus 1.04, 1.03 to 1.05), but the increase in HbA1c was associated with a higher risk for people without diabetes than for people with diabetes (aORs 1.09, 1.07 to 1.11 versus 1.04, 1.03 to 1.04).ConclusionsThe statistically significant changes in weight and glycaemic control started three years before pancreatic cancer diagnosis but varied according to the diabetes status. The information from this study could be used to detect pancreatic cancer earlier than is currently achieved. However, regular BMI and HbA1c measurements are required to facilitate future research and implementation in clinical practice.

Effectiveness and cost-effectiveness of referral to a commercial open group behavioural weight management programme in adults with overweight and obesity: 5-year follow-up of the WRAP randomised controlled trial

There is evidence that commercially available behavioural weight management programmes can lead to short-term weight loss and reductions in glycaemia. Here, we aimed to provide the 5-year impact and cost-effectiveness of these interventions compared with a brief intervention. WRAP was a non-blinded, parallel-group randomised controlled trial (RCT). We recruited from primary care practices in England and randomly assigned participants to one of three interventions (brief intervention, 12-week open-group behavioural programme [WW, formerly Weight Watchers], or a 52-week open-group WW behavioural programme) in an uneven (2:5:5) allocation. Participants were followed up 5 years after randomisation using data from measurement visits at primary care practices or a research centre, review of primary care electronic medical notes, and self-report questionnaires. The primary outcome was change in weight at 5 years follow-up, assessed using analysis of covariance. We also estimated cost-effectiveness of the intervention. This study is registered at Current Controlled Trials, ISRCTN64986150. Between Oct 18, 2012, and Feb 10, 2014, we recruited 1269 eligible participants (two participants were randomly assigned but not eligible and therefore excluded) and 1040 (82%) consented to be approached about additional follow-up and to have their medical notes reviewed at 5 years. The primary outcome (weight) was ascertained for 871 (69%) of 1267 eligible participants. Mean duration of follow-up was 5·1 (SD 0·3) years. Mean weight change from baseline to 5 years was -0·46 (SD 8·31) kg in the brief intervention group, -1·95 (9·55) kg in the 12-week programme group, and -2·67 (9·81) kg in the 52-week programme. The adjusted difference in weight change was -1·76 (95% CI -3·68 to 0·17) kg between the 52-week programme and the brief intervention; -0·80 (-2·13 to 0·54) kg between the 52-week and the 12-week programme; and -0·96 (-2·90 to 0·97) kg between the 12-week programme and the brief intervention. During the trial, the 12-week programme incurred the lowest cost and produced the highest quality-adjusted life-years (QALY). Simulations beyond 5 years suggested that the 52-week programme would deliver the highest QALYs at the lowest cost and would be the most cost-effective. No participants reported adverse events related to the intervention. Although the difference in weight change between groups was not statistically significant, some weight loss was maintained at 5 years after an open-group behavioural weight management programme. Health economic modelling suggests that this could have important implications to reduce the incidence of weight-related disease and these interventions might be cost-saving. The UK National Institute for Health and Care Research Programme Grants for Applied Research and the Medical Research Council.

Fecal Immunochemical Testing in Patients With Low-Risk Symptoms of Colorectal Cancer: A Diagnostic Accuracy Study.

The fecal immunochemical test (FIT) is recommended for triaging primary care patients in England with low-risk symptoms of colorectal cancer (CRC). The evidence underpinning recommendations by the National Institute for Health and Care Excellence had limitations, with a paucity of primary care evidence. This study examines the diagnostic accuracy of FIT in a defined low-risk symptom primary care population. Consecutive symptomatic adult patients referred for a FIT between October and December 2019 were included. Patients were derived from 225 primary care practices in England. Serious colorectal diseases (CRC, high-risk polyps, and inflammatory bowel disease [IBD]) were identified through patient follow-up over 18 months, using both primary and secondary healthcare records. Performance characteristics of FIT are reported according to differing thresholds, including the currently recommended threshold of ≥10 μg hemoglobin per gram of feces (μg/g). A total of 3,506 patients were included in the final analysis. Of these, 708 had a positive FIT result (≥10 μg/g). The prevalence of CRC was 1.3%. FIT positivity declined from 20.2% to 5.8% and 4.5% at cutoffs of 10, 80, and 120 μg/g, respectively. The sensitivity of FIT at ≥10 μg/g to detect CRC was 91.1% (95% CI, 77.9%-97.1%); its specificity was 80.7% (95% CI, 79.3%-82.0%); the positive predictive value (PPV) was 5.8% (95% CI, 4.2%-7.8%); and the negative predictive value (NPV) was 99.9% (95% CI, 99.6%-99.95%). The area under the receiver operating characteristic curve was 0.93 (0.91-0.96). PPV and specificity increased, whereas sensitivity and NPV decreased when serious colorectal diseases (CRC, high-risk polyps, and IBD) were combined. Age, sex, socioeconomic deprivation, and anemia did not significantly influence FIT sensitivity on subgroup analysis. Utilization of FIT at a threshold ≥10 μg/g can safely triage patients with low-risk symptoms in primary care, with negative results effectively ruling out CRC.

Disparity in association of obesity measures with ankle and brachial systolic blood pressures in Europeans and South Asians

Obesity causes increases in brachial systolic-blood-pressures (SBP), risks of type 2 diabetes (T2DM) and cardiovascular diseases (CVD). Brachial and ankle SBPs have differential relationship with T2DM and CVD. Our objective was to study the relationship of obesity measures with brachial and ankle SBPs. A population of 1098 adults (South Asians n = 699; 41.70% male and 58.3% female) were recruited over 5 years from primary care practices in England. Their four limbs SBPs were measured using Doppler machine and body-mass-index (BMI) and waist-to-height-ratio (WHtR) calculated. Linear regressions were performed between SBPs and obesity measures, after adjustments for sex, age, ethnicity, T2DM and CVD. The mean age of all participants was 51.3 (SD = 17.2), European was 57.7 (SD 17.2) and South Asian was 47.8 (SD = 16.1). The left posterior tibial [Beta = 1.179, P = 4.559 × 10−15] and the right posterior tibial SBP [Beta = 1.178, P = 1.114 × 10−13] most significantly associated with the BMI. In South Asians, although the left brachial [Beta = 25.775, P = 0.032] and right brachial SBP [Beta = 22.792, P = 0.045] were associated to the WHtR, the left posterior tibial SBP [Beta = 39.894, P = 0.023], association was the strongest. For the first time, we have demonstrated that ankle SBPs had significant association with generalised obesity than brachial systolic blood pressures (SBP), irrespective of ethnicity. However, with respect to visceral obesity, the association with ankle SBP was more significant in South Asians compared to Europeans.

Characteristics of New Users of Single- and Multiple-Inhaler Triple Therapy for COPD in Primary Care in England.

PurposeInhaled triple therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) who have poorly controlled symptoms and to reduce the risk of exacerbations. This study assessed the clinical characteristics of new users of single- and multiple-inhaler triple therapy (SITT and MITT) treated in a primary care setting in England.Patients and MethodsThis cross-sectional, observational study used data from an electronic health record database (CPRD Aurum) of COPD patients registered with a primary care practice in England, with linkage to a secondary care database. Patients were required to have initiated a new triple therapy (index) between November 2017 and November 2018 and have ≥12 months of available medical history prior to the index date.ResultsIn total, 3536 patients initiated fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) SITT for the first time: 65% had a Medical Research Council (MRC) dyspnea score ≥3, 45% had forced expiratory volume in 1 second (FEV1)% predicted <50%, and 64% had a moderate or severe exacerbation in the previous 12 months. The majority (83%) of new FF/UMEC/VI users had a history of MITT use. Immediately prior to FF/UMEC/VI initiation, 46% received MITT, 25% received an inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA), 12% received long-acting muscarinic antagonist (LAMA)/LABA, and 14% stepped up directly from LAMA monotherapy. A second cohort of 6540 patients initiated triple therapy (SITT or MITT) for the first time. COPD severity (airflow limitation, exacerbation history) was worse among patients initiating SITT versus MITT. In the 12 months before triple-therapy initiation, ICS/LABA was the most common treatment; a step up from LAMA/LABA was more common among patients initiating FF/UMEC/VI (34%) or beclomethasone/formoterol/glycopyrronium bromide SITT (25%) than MITT (14%).ConclusionFirst-time triple therapy was frequently initiated in patients with COPD inadequately controlled on maintenance therapy. General practitioners in England generally identify appropriate patients who require initiation of triple therapy.

POS-282 ASSOCIATION BETWEEN PRIMARY CARE CODING OF CHRONIC KIDNEY DISEASE (CKD) AND SUBSEQUENT HOSPITALISATIONS AND DEATH: A COHORT ANALYSIS USING NATIONAL AUDIT DATA

In UK primary care, there are payment incentives to test for chronic kidney disease (CKD) and to add CKD-specific diagnosis codes to the electronic patient health record to establish a register of stage 3-5 CKD patients. The National Chronic Kidney Disease Audit (NCKDA) in England and Wales found that not all patients with biochemical evidence of CKD stages 3-5 were coded; those who were not coded had less cardiovascular preventative care than those who were coded. Practice-level coding is less likely to be influenced by individual patient characteristics and is therefore potentially less confounded than analyses using patient-specific coding decisions. We investigated the association between practice-level coding of CKD and individual adverse outcomes to quantify the effects of coding in patients with CKD. We conducted a retrospective cohort study linking NCKDA primary care records with Hospital Episode Statistics (HES) admissions and Office for National Statistics (ONS) mortality data in England. Patients with confirmed CKD (2 x estimated glomerular filtration rate < 60 ml/min/1.73m2, separated by ≥ 90 days, with the latest measure within 2 years prior to data extraction) were included, excluding those with coded initiation of renal replacement therapy. Cox proportional hazards regression models with splines, adjusted for practice characteristics, were used to investigate the association between practice percentage of confirmed CKD cases with a stage 3-5 CKD code and patient outcomes: hospitalisation for cardiovascular (CV) events, hospitalisation for heart failure (HF), hospitalisation with acute kidney injury (AKI) and all-cause mortality. 167,208 patients from 637 primary care practices in England were included in analysis, with a median follow up time of 3.8 years for hospitalisations and 4.3 years for deaths. Patient characteristics were well balanced in the two-thirds of most typically performing practices (55% to 88% coded CKD), but with slight differences at the extremes. Rates of CV and HF admissions were significantly reduced as practice CKD coding performance increased (Figure 1). In practices coding 60% of CKD cases, patients had a 4.8% (0.9%, 9.0%) higher hazard of CV hospitalisations and an 8.6% (1.5%, 16.1%) higher hazard of HF hospitalisations than the average practice (74% coded). Trends of a small reduction in AKI but no substantial change in risk of deaths were also observed as CKD coding increased. Figure 1. Percent difference in hazard rates of outcomes according to practice percent coded CKD, compared to median practice coding (74% coded) among patients with confirmed CKD in the two-thirds of most typically performing practices (55% to 88% coded). Adjusted for practice characteristics: mean age, percent male, median rank of index of multiple deprivation, diabetes prevalence, hypertension prevalence, CVD prevalence, percent of CKD cases at stages 3b-5, percent of CKD patients admitted for COPD in last 3 years, percent of CKD patients admitted for cancer in last 3 years, percent GFR test in last year in diabetes, percent GFR test in last year in CKD, percent of adult population with CKD Increased CKD coding in primary care and subsequent care efforts appear to play a role in improving patient outcomes, although residual confounding due to unobserved practice characteristics cannot be ruled out.

The dynamics of frailty development and progression in older adults in primary care in England (2006\u20132017): a retrospective cohort profile

BackgroundFrailty is a common condition in older adults and has a major impact on patient outcomes and service use. Information on the prevalence in middle-aged adults and the patterns of progression of frailty at an individual and population level is scarce. To address this, a cohort was defined from a large primary care database in England to describe the epidemiology of frailty and understand the dynamics of frailty within individuals and across the population. This article describes the structure of the dataset, cohort characteristics and planned analyses.MethodsRetrospective cohort study using electronic health records. Participants were aged ≥50 years registered in practices contributing to the Oxford Royal College of General Practitioners Research and Surveillance Centre between 2006 to 2017. Data include GP practice details, patient sociodemographic and clinical characteristics, twice-yearly electronic Frailty Index (eFI), deaths, medication use and primary and secondary care health service use. Participants in each cohort year by age group, GP and patient characteristics at cohort entry are described.ResultsThe cohort includes 2,177,656 patients, contributing 15,552,946 person-years, registered at 419 primary care practices in England. The mean age was 61 years, 52.1% of the cohort was female, and 77.6% lived in urban environments. Frailty increased with age, affecting 10% of adults aged 50–64 and 43.7% of adults aged ≥65. The prevalence of long-term conditions and specific frailty deficits increased with age, as did the eFI and the severity of frailty categories.ConclusionA comprehensive understanding of frailty dynamics will inform predictions of current and future care needs to facilitate timely planning of appropriate interventions, service configurations and workforce requirements. Analysis of this large, nationally representative cohort including participants aged ≥50 will capture earlier transitions to frailty and enable a detailed understanding of progression and impact. These results will inform novel simulation models which predict future health and service needs of older people living with frailty.Study registrationRegistered on www.clinicaltrials.gov October 25th 2019, NCT04139278.

Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform

SummaryBackgroundCOVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England.MethodsWe conducted an observational cohort study of adults (aged ≥18 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region.FindingsOf 17 288 532 adults included in the study (excluding care home residents), 10 877 978 (62·9%) were White, 1 025 319 (5·9%) were South Asian, 340 912 (2·0%) were Black, 170 484 (1·0%) were of mixed ethnicity, 320 788 (1·9%) were of other ethnicity, and 4 553 051 (26·3%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1·08 [95% CI 1·07–1·09]), Black group (1·08 [1·06–1·09]), and mixed ethnicity group (1·04 [1·02–1·05]) and was decreased in the other ethnicity group (0·77 [0·76–0·78]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1·99 [1·94–2·04]), Black group (1·69 [1·62–1·77]), mixed ethnicity group (1·49 [1·39–1·59]), and other ethnicity group (1·20 [1·14–1·28]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1·48 [1·41–1·55], Black group 1·78 [1·67–1·90], mixed ethnicity group 1·63 [1·45–1·83], other ethnicity group 1·54 [1·41–1·69]), COVID-19-related ICU admission (2·18 [1·92–2·48], 3·12 [2·65–3·67], 2·96 [2·26–3·87], 3·18 [2·58–3·93]), and death (1·26 [1·15–1·37], 1·51 [1·31–1·71], 1·41 [1·11–1·81], 1·22 [1·00–1·48]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories.InterpretationSome minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination.FundingMedical Research Council.

Associations between attainment of incentivized primary care indicators and incident sight-threatening diabetic retinopathy in England: A population-based historical cohort study.

AimTo examine the impact of attainment of primary care diabetes clinical indicators on progression to sight‐threatening diabetic retinopathy (STDR) among those with mild non‐proliferative diabetic retinopathy (NPDR).Materials and MethodsAn historical cohort study of 18,978 adults (43.63% female) diagnosed with type 2 diabetes before 1 April 2010 and mild NPDR before 1 April 2011 was conducted. The data were obtained from the UK Clinical Practice Research Datalink during 2010‐2017, provided by 330 primary care practices in England. Exposures included attainment of the Quality and Outcomes Framework HbA1c (≤59 mmol/mol [≤7.5%]), blood pressure (≤140/80 mmHg) and cholesterol (≤5 mmol/L) indicators in the financial year 2010‐2011, as well as the number of National Diabetes Audit processes completed in 2010‐2011. The outcome was time to incident STDR. Nearest neighbour propensity score matching was undertaken, and univariable and multivariable Cox proportional hazards models were then fitted using the matched samples. Concordance statistics were calculated for each model.ResultsA total of 1037 (5.5%) STDR diagnoses were observed over a mean follow‐up of 3.6 (SD 2.0) years. HbA1c, blood pressure and cholesterol indicator attainment were associated with lower rates of STDR (adjusted hazard ratios [95% CI] 0.64 [0.55‐0.74; p < .001], 0.83 [0.72‐0.94; p = .005] and 0.80 [0.66‐0.96; p = .015], respectively).ConclusionsOur findings provide support for meeting appropriate indicators for the management of type 2 diabetes in primary care to bring a range of benefits, including improved health outcomes—such as a reduction in the risk of STDR—for people with type 2 diabetes.

Non-benzodiazepine hypnotic use for sleep disturbance in people aged over 55 years living with dementia: a series of cohort studies.

Sleep disturbance affects around 60% of people living with dementia and can negatively affect their quality of life and that of their carers. Hypnotic Z-drugs (zolpidem, zopiclone and zaleplon) are commonly used to treat insomnia, but their safety and efficacy have not been evaluated for people living with dementia. To estimate the benefits and harms of Z-drugs in people living with dementia with sleep disturbance. A series of observational cohort studies using existing data from (1) primary care linked to hospital admission data and (2) clinical cohort studies of people living with dementia. Primary care study - Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics mortality data. Clinical cohort studies - the Resource Use and Disease Course in Dementia - Nursing Homes (REDIC) study, National Alzheimer's Coordinating Centre (NACC) clinical data set and the Improving Well-being and Health for People with Dementia (WHELD) in nursing homes randomised controlled trial. Primary care study - 371 primary care practices in England. Clinical cohort studies - 47 nursing homes in Norway, 34 Alzheimer's disease centres in the USA and 69 care homes in England. Primary care study - NHS England primary care patients diagnosed with dementia and aged > 55 years, with sleep disturbance or prescribed Z-drugs or low-dose tricyclic antidepressants, followed over 2 years. Clinical cohort studies - people living with dementia consenting to participate, followed over 3 years, 12 years and 9 months, for REDIC, NACC and WHELD, respectively. The primary exposure was prescription or use of Z-drugs. Secondary exposures included prescription or use of benzodiazepines, low-dose tricyclic antidepressants and antipsychotics. Falls, fractures, infection, stroke, venous thromboembolism, mortality, cognitive function and quality of life. There were insufficient data to investigate sleep disturbance. The primary care study and combined clinical cohort studies included 6809 and 18,659 people living with dementia, with 3089 and 914 taking Z-drugs, respectively. New Z-drug use was associated with a greater risk of fractures (hazard ratio 1.40, 95% confidence interval 1.01 to 1.94), with risk increasing with greater cumulative dose (p = 0.002). The hazard ratio for Z-drug use and hip fracture was 1.59 (95% confidence interval 1.00 to 2.53) and for mortality was 1.34 (95% confidence interval 1.10 to 1.64). No excess risks of falls, infections, stroke or venous thromboembolism were detected. Z-drug use also did not have an impact on cognition, neuropsychiatric symptoms, disability or quality of life. Primary care study - possible residual confounding because of difficulties in identifying patients with sleep disturbance and by dementia severity. Clinical cohort studies - the small numbers of people living with dementia taking Z-drugs and outcomes not necessarily being measured before Z-drug initiation restricted analyses. We observed a dose-dependent increase in fracture risk, but no other harms, with Z-drug use in dementia. However, multiple outcomes were examined, increasing the risk of false-positive findings. The mortality association was unlikely to be causal. Further research is needed to confirm the increased fracture risk. Decisions to prescribe Z-drugs may need to consider the risk of fractures, balanced against the impact of improved sleep for people living with dementia and that of their carers. Our findings suggest that when Z-drugs are prescribed, falls prevention strategies may be needed, and that the prescription should be regularly reviewed. More research is needed on safe and effective management strategies for sleep disturbance in people living with dementia. This study is registered as European Union electronic Register of Post-Authorisation Studies (EU PAS) 18006. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 1. See the NIHR Journals Library website for further project information.

Analysis of the trend in community prescribing of RAAS inhibitors during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has sparked novel research and insights, but also concerns and anxiety regarding established practices. Early into the pandemic, public and scientific concern was raised regarding the role of renin-angiotensin- aldosterone system (RAAS) inhibitors on the susceptibility to COVID-19 given their effect on angiotensin-converting enzyme 2 (ACE-2), the host receptor for the virus. This gathered media attention globally, despite several health boards encouraging the ongoing use of these medications. We aimed to investigate whether, despite advice supporting continued use of these medications, there was a change in prescribing practices for RAAS inhibitors in general practice. Data were collated from the NHS digital platform, which provides monthly practice-level prescribing information for all primary care practices in England. We performed an interrupted time-series analysis on national-level prescribing data comparing time-series coefficients pre- and post-March 2020 with metformin used as a control. We find that from March to December 2020, prescribing rates of RAAS inhibitors were reduced relative to the previous time-series trend. This finding persisted after adjustment for rates of metformin prescription. This suggests that there was a change in prescribing behaviour during the COVID-19 pandemic, which may be linked to the public and scientific concerns during this time.

Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life

There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure. To compare low-dose digoxin with bisoprolol (a β-blocker). Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019. Digoxin (n = 80; dose range, 62.5-250 μg/d; mean dose, 161 μg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d). The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting. Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, -1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, -2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P < .001). At 12 months, 8 of 20 outcomes were significantly different (all favoring digoxin), with a median NT-proBNP level of 960 pg/mL (interquartile range, 626 to 1531 pg/mL) in the digoxin group vs 1250 pg/mL (interquartile range, 847 to 1890 pg/mL) in the bisoprolol group (ratio of geometric means, 0.77 [95% CI, 0.64 to 0.92]; P = .005). Adverse events were less common with digoxin; 20 patients (25%) in the digoxin group had at least 1 AE vs 51 patients (64%) in the bisoprolol group (P < .001). There were 29 treatment-related AEs and 16 serious AEs in the digoxin group vs 142 and 37, respectively, in the bisoprolol group. Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points. ClinicalTrials.gov Identifier: NCT02391337 and clinicaltrialsregister.eu Identifier: 2015-005043-13.

Investigating the mechanism of impact and differential effect of the Quality Premium scheme on antibiotic prescribing in England: a longitudinal study.

BackgroundIn 2017, approximately 73% of antibiotics in England were prescribed from primary care practices. It has been estimated that 9%–23% of antibiotic prescriptions between 2013 and 2015 were inappropriate. Reducing antibiotic prescribing in primary care was included as one of the national priorities in a financial incentive scheme in 2015–2016.AimTo investigate whether the effects of the Quality Premium (QP), which provided performance-related financial incentives to clinical commissioning groups (CCGs), could be explained by practice characteristics that contribute to variations in antibiotic prescribing.Design & settingLongitudinal monthly prescribing data were analysed for 6251 primary care practices in England from April 2014 to March 2016.MethodLinear generalised estimating equations models were fitted, examining the effect of the 2015–2016 QP on the number of antibiotic items per specific therapeutic group age–sex related prescribing unit (STAR-PU) prescribed, adjusting for seasonality and months since implementation. Consistency of effects after further adjustment for variations in practice characteristics were also examined, including practice workforce, comorbidities prevalence, prescribing rates of non-antibiotic drugs, and deprivation.ResultsAntibiotics prescribed in primary care practices in England reduced by -0.172 items per STAR-PU (95% confidence interval [CI] = -0.180 to -0.171) after 2015–2016 QP implementation, with slight increases in the months following April 2015 (+0.014 items per STAR-PU; 95% CI = +0.013 to +0.014). Adjusting the model for practice characteristics, the immediate and month-on-month effects following implementation remained consistent, with slight attenuation in immediate reduction from -0.172 to -0.166 items per STAR-PU. In subgroup analysis, the QP effect was significantly greater among the top 20% prescribing practices (interaction p<0.001). Practices with low workforce and those with higher diabetes prevalence had greater reductions in prescribing following 2015–2016 QP compared with other practices (interaction p<0.001).ConclusionIn high-prescribing practices, those with low workforce and high diabetes prevalence had more reduction following the QP compared with other practices, highlighting the need for targeted support of these practices and appropriate resourcing of primary care.

Association Between Atopic Eczema and Cancer in England and Denmark

Associations between atopic eczema and cancer are unclear, with competing theories that increased immune surveillance decreases cancer risk and that immune stimulation increases cancer risk. Establishing baseline cancer risk in people with atopic eczema is important before exploring the association between new biologic drugs for atopic eczema and cancer risk. To investigate whether atopic eczema is associated with cancer. Matched cohort studies were conducted from January 2, 1998, to March 31, 2016, in England and from January 1, 1982, to June 30, 2016, in Denmark. We conducted our analyses between July 2018 and July 2019. The setting was English primary care and nationwide Danish data. Participants with atopic eczema (adults only in England and any age in Denmark) were matched on age, sex, and calendar period (as well as primary care practice in England only) to those without atopic eczema. Atopic eczema. Overall cancer risk and risk of specific cancers were compared in people with and without atopic eczema. In England, matched cohorts included 471 970 individuals with atopic eczema (median [IQR] age, 41.1 [24.9-60.7] years; 276 510 [58.6%] female) and 2 239 775 individuals without atopic eczema (median [IQR] age, 39.8 [25.9-58.4] years; 1 301 074 [58.1%] female). In Denmark, matched cohorts included 44 945 individuals with atopic eczema (median [IQR] age, 13.7 [1.7-21.1] years; 22 826 [50.8%] female) and 445 673 individuals without atopic eczema (median [IQR] age, 13.5 [1.7-20.8] years; 226 323 [50.8%] female). Little evidence was found of associations between atopic eczema and overall cancer (adjusted hazard ratio [HR], 1.04; 99% CI, 1.02-1.06 in England and 1.05; 99% CI, 0.95-1.16 in Denmark) or for most specific cancers. However, noncutaneous lymphoma risk was increased in people with atopic eczema in England (adjusted HR, 1.19; 99% CI, 1.07-1.34 for non-Hodgkin lymphoma [NHL] and 1.48; 99% CI, 1.07-2.04 for Hodgkin lymphoma). Lymphoma risk was increased in people with greater eczema severity vs those without atopic eczema (NHL adjusted HR, 1.06; 99% CI, 0.90-1.25 for mild eczema; 1.24; 99% CI, 1.04-1.48 for moderate eczema; and 2.08; 99% CI, 1.42-3.04 for severe eczema). Danish point estimates also showed increased lymphoma risk in people with moderate to severe eczema compared with those without atopic eczema (minimally adjusted HR, 1.31; 99% CI, 0.76-2.26 for NHL and 1.35; 99% CI, 0.65-2.82 for Hodgkin lymphoma), but the 99% CIs were wide. The findings from 2 large population-based studies performed in different settings do not support associations between atopic eczema and most cancers. However, an association was observed between atopic eczema and lymphoma, particularly NHL, that increased with eczema severity. This finding warrants further study as new immunomodulatory systemic therapeutics are brought to market that may alter cancer risk.