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IntroductionPeople with serious mental illness (SMI), which includes people with diagnoses of schizophrenia spectrum and bipolar disorders, face significant health inequality. This includes a life expectancy reduced by 15–20 years mostly due to premature cardiovascular disease (CVD) compared with the general population. Excess weight gain and related comorbidities are preventable risk factors for CVD. To improve the understanding and management of CVD in people with SMI, we will examine the association between SMI and: (1) weight change; (2) cardio-metabolic risk factors for CVD; and (3) incidence of and mortality from CVD. We will also (4) examine the incidence of referral to weight management services for people with SMI compared with people without SMI.Methods and analysisIn this retrospective cohort study, we will link general practice records from the UK Clinical Practice Research Datalink Aurum database. We will establish a cohort of patients diagnosed with SMI between 1998 and 2020 who are matched with up to four controls on age, sex, general practice and calendar year. We will use multivariable mixed-effects linear regression models and Cox proportional hazard models with sequential adjustment for potential confounders identified by separate directed acyclic graphs.Ethics and disseminationThis study has been reviewed and approved by the Independent Scientific Advisory Committee for Medicines and Healthcare products Regulatory Agency database research. The results will be published in a peer-reviewed journal.

Background One-stop clinics provide comprehensive diagnostic testing in one outpatient appointment. They could benefit patients with conditions, such as cancer, whose outcomes are improved by early diagnosis, and bring efficiency savings for health systems. Objective To assess the use and outcomes of one-stop clinics for symptoms where cancer is a possible diagnosis. Design and setting Systematic review of studies reporting use and outcomes of one-stop clinics in primary care patients. Method We searched MEDLINE, Embase, and Cochrane Library for studies assessing one-stop clinics for adults referred after presenting to primary care with any symptom that could be indicative of cancer. Study selection was carried out independently in duplicate with disagreements resolved through discussion. Results Twenty-nine studies were identified, most were conducted in the UK and observational in design. Few included a comparison arm. A pooled comparison of the cancer conversion rate of one-stop and multi-stop clinics was only possible for breast symptoms, and we found no significant difference. One-stop clinics were associated with significant reductions in the interval from referral to testing (15 versus 75 days) and more patients diagnosed on the same day (79% versus 25%) compared to multi-stop pathways. The majority of patients and GPs found one-stop clinics to be acceptable. Conclusion This review found one-stop clinics were associated with reduced time from referral to testing, increased same day diagnoses, and were acceptable to patients and GPs. Our conclusions are limited by high levels of heterogeneity, scarcity of comparator groups, and the overwhelmingly observational nature of included studies.

Background Long-term monitoring is important in chronic condition management. Despite considerable costs of monitoring, there is no or poor evidence on how, what and when to monitor. The aim of this study was to improve understanding, methods, evidence base and practice of clinical monitoring in primary care, focusing on two areas: chronic kidney disease and chronic heart failure. Objectives The research questions were as follows: does the choice of test affect better care while being affordable to the NHS? Can the number of tests used to manage individuals with early-stage kidney disease, and hence the costs, be reduced? Is it possible to monitor heart failure using a simple blood test? Can this be done using a rapid test in a general practitioner consultation? Would changes in the management of these conditions be acceptable to patients and carers? Design Various study designs were employed, including cohort, feasibility study, Clinical Practice Research Datalink analysis, seven systematic reviews, two qualitative studies, one cost-effectiveness analysis and one cost recommendation. Setting This study was set in UK primary care. Data sources Data were collected from study participants and sourced from UK general practice and hospital electronic health records, and worldwide literature. Participants The participants were NHS patients (Clinical Practice Research Datalink: 4.5 million patients), chronic kidney disease and chronic heart failure patients managed in primary care (including 750 participants in the cohort study) and primary care health professionals. Interventions The interventions were monitoring with blood and urine tests (for chronic kidney disease) and monitoring with blood tests and weight measurement (for chronic heart failure). Main outcome measures The main outcomes were the frequency, accuracy, utility, acceptability, costs and cost-effectiveness of monitoring. Results Chronic kidney disease: serum creatinine testing has increased steadily since 1997, with most results being normal (83% in 2013). Increases in tests of creatinine and proteinuria correspond to their introduction as indicators in the Quality and Outcomes Framework. The Chronic Kidney Disease Epidemiology Collaboration equation had 2.7% greater accuracy (95% confidence interval 1.6% to 3.8%) than the Modification of Diet in Renal Disease equation for estimating glomerular filtration rate. Estimated annual transition rates to the next chronic kidney disease stage are ≈ 2% for people with normal urine albumin, 3–5% for people with microalbuminuria (3–30 mg/mmol) and 3–12% for people with macroalbuminuria (> 30 mg/mmol). Variability in estimated glomerular filtration rate-creatinine leads to misclassification of chronic kidney disease stage in 12–15% of tests in primary care. Glycaemic-control and lipid-modifying drugs are associated with a 6% (95% confidence interval 2% to 10%) and 4% (95% confidence interval 0% to 8%) improvement in renal function, respectively. Neither estimated glomerular filtration rate-creatinine nor estimated glomerular filtration rate-Cystatin C have utility in predicting rate of kidney function change. Patients viewed phrases such as ‘kidney damage’ or ‘kidney failure’ as frightening, and the term ‘chronic’ was misinterpreted as serious. Diagnosis of asymptomatic conditions (chronic kidney disease) was difficult to understand, and primary care professionals often did not use ‘chronic kidney disease’ when managing patients at early stages. General practitioners relied on Clinical Commissioning Group or Quality and Outcomes Framework alerts rather than National Institute for Health and Care Excellence guidance for information. Cost-effectiveness modelling did not demonstrate a tangible benefit of monitoring kidney function to guide preventative treatments, except for individuals with an estimated glomerular filtration rate of 60–90 ml/minute/1.73 m2, aged < 70 years and without cardiovascular disease, where monitoring every 3–4 years to guide cardiovascular prevention may be cost-effective. Chronic heart failure: natriuretic peptide-guided treatment could reduce all-cause mortality by 13% and heart failure admission by 20%. Implementing natriuretic peptide-guided treatment is likely to require predefined protocols, stringent natriuretic peptide targets, relative targets and being located in a specialist heart failure setting. Remote monitoring can reduce all-cause mortality and heart failure hospitalisation, and could improve quality of life. Diagnostic accuracy of point-of-care N-terminal prohormone of B-type natriuretic peptide (sensitivity, 0.99; specificity, 0.60) was better than point-of-care B-type natriuretic peptide (sensitivity, 0.95; specificity, 0.57). Within-person variation estimates for B-type natriuretic peptide and weight were as follows: coefficient of variation, 46% and coefficient of variation, 1.2%, respectively. Point-of-care N-terminal prohormone of B-type natriuretic peptide within-person variability over 12 months was 881 pg/ml (95% confidence interval 380 to 1382 pg/ml), whereas between-person variability was 1972 pg/ml (95% confidence interval 1525 to 2791 pg/ml). For individuals, monitoring provided reassurance; future changes, such as increased testing, would be acceptable. Point-of-care testing in general practice surgeries was perceived positively, reducing waiting time and anxiety. Community heart failure nurses had greater knowledge of National Institute for Health and Care Excellence guidance than general practitioners and practice nurses. Health-care professionals believed that the cost of natriuretic peptide tests in routine monitoring would outweigh potential benefits. The review of cost-effectiveness studies suggests that natriuretic peptide-guided treatment is cost-effective in specialist settings, but with no evidence for its value in primary care settings. Limitations No randomised controlled trial evidence was generated. The pathways to the benefit of monitoring chronic kidney disease were unclear. Conclusions It is difficult to ascribe quantifiable benefits to monitoring chronic kidney disease, because monitoring is unlikely to change treatment, especially in chronic kidney disease stages G3 and G4. New approaches to monitoring chronic heart failure, such as point-of-care natriuretic peptide tests in general practice, show promise if high within-test variability can be overcome. Future work The following future work is recommended: improve general practitioner–patient communication of early-stage renal function decline, and identify strategies to reduce the variability of natriuretic peptide. Study registration This study is registered as PROSPERO CRD42015017501, CRD42019134922 and CRD42016046902. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 10. See the NIHR Journals Library website for further project information.

The effect of the 2020 pandemic, and of the national measures introduced to control it, is not yet fully understood. The aim of this study was to investigate how different types of primary care data can help quantify the effect of the coronavirus disease (COVID-19) crisis on mental health. A retrospective cohort study investigated changes in weekly counts of mental health consultations and prescriptions. The data were extracted from one the UK’s largest primary care databases between January 1st 2015 and October 31st 2020 (end of follow-up). The 2020 trends were compared to the 2015-19 average with 95% confidence intervals using longitudinal plots and analysis of covariance (ANCOVA). A total number of 504 practices (7,057,447 patients) contributed data. During the period of national restrictions, on average, there were 31% (3957 ± 269, p < 0.001) fewer events and 6% (4878 ± 1108, p < 0.001) more prescriptions per week as compared to the 2015-19 average. The number of events was recovering, increasing by 75 (± 29, p = 0.012) per week. Prescriptions returned to the 2015-19 levels by the end of the study (p = 0.854). The significant reduction in the number of consultations represents part of the crisis. Future service planning and quality improvements are needed to reduce the negative effect on health and healthcare.

Objectives To mitigate risk of mortality from coronavirus 2019 infection (COVID-19), the UK government recommended ‘shielding’ of vulnerable people through self-isolation for 12 weeks. Methods A retrospective cohort study using a nationally representative English primary care database comparing people aged >= 40 years who were recorded as being advised to shield using a fixed ratio of 1:1, matching to people with the same diagnoses not advised to shield (n = 77,360 per group). Time-to-death was compared using Cox regression, reporting the hazard ratio (HR) of mortality between groups. A sensitivity analysis compared exact matched cohorts (n = 24,752 shielded, n = 61,566 exact matches). Results We found a time-varying HR of mortality between groups. In the first 21 days, the mortality risk in people shielding was half those not (HR = 0.50, 95%CI:0.41–0.59. p

BackgroundThe complexity of general practice consultations may be increasing and varies in different settings. A measure of complexity is required to test these hypotheses.AimTo develop a valid measure of general practice consultation complexity applicable to routine medical records.Design and settingDelphi study to select potential indicators of complexity followed by a cross-sectional study in English general practices to develop and validate a complexity measure.MethodThe online Delphi study over two rounds identified potential indicators of consultation complexity. The cross-sectional study used an age–sex stratified random sample of patients and general practice face-to-face consultations from 2013/2014 in the Clinical Practice Research Datalink. The authors explored independent relationships between each indicator and consultation duration using mixed-effects regression models, and revalidated findings using data from 2017/2018. The proportion of complex consultations in different age–sex groups was assessed.ResultsA total of 32 GPs participated in the Delphi study. The Delphi panel endorsed 34 of 45 possible complexity indicators after two rounds. After excluding factors because of low prevalence or confounding, 17 indicators were retained in the cross-sectional study. The study used data from 173 130 patients and 725 616 face-to-face GP consultations. On defining complexity as the presence of any of these 17 factors, 308 370 consultations (42.5%) were found to be complex. Mean duration of complex consultations was 10.49 minutes, compared to 9.64 minutes for non-complex consultations. The proportion of complex consultations was similar in males and females but increased with age.ConclusionThe present consultation complexity measure has face and construct validity. It may be useful for research, management and policy, and for informing decisions about the range of resources needed in different practices.

Hypertension has been identified as a risk factor for coronavirus disease 2019 (COVID-19) and associated adverse outcomes. This study examined the association between preinfection blood pressure (BP) control and COVID-19 outcomes using data from 460 general practices in England. Eligible patients were adults with hypertension who were tested or diagnosed with COVID-19. BP control was defined by the most recent BP reading within 24 months of the index date (January 1, 2020). BP was defined as controlled (

Objective To investigate feasibility and acceptability of self-testing for proteinuria during pregnancy. Study design Mixed methods approach which included: an accuracy study where pregnant women (n = 100) and healthcare professionals (n = 96) tested seven synthetic protein samples and completed a questionnaire, a feasibility study where pregnant women who were self-monitoring their blood pressure were asked to self-test for proteinuria (n = 30), and an online questionnaire about women’s experiences of self-testing (n = 200). Main outcome measures Sensitivity and specificity of testing and questionnaire results. Results There were no significant differences in the accuracy of synthetic sample testing by pregnant women (sensitivity 0.81 (95% confidence intervals (CI) 0.78–0.85), specificity 0.93 (95% CI 0.91–0.95)) and healthcare professionals: (sensitivity 0.83 (95% CI 0.79–0.86), specificity 0.92 (95% CI 0.90–0.94)). Automated readers had significantly better sensitivity (0.94 (0.91–0.97) (p ≤ .001 in each case), but worse specificity 0.78 (0.69–0.85). Similar results were gained using self-tested urine samples compared to staff-testing using a reference standard of laboratory urine protein-creatinine ratio (uPCR). Women who completed the online survey with experience of self-testing (n = 39, 20%) generally found it easy, and with support from healthcare professionals felt it improved involvement in their care and reduced anxiety. Conclusions Self-testing for proteinuria by pregnant women had similar accuracy to healthcare professional testing and was acceptable to both groups. Self-testing of urine combined with self-monitoring of blood pressure could provide a useful adjunct to clinic-based surveillance for the detection of pre-eclampsia. Such novel strategies warrant further research.

ObjectivesTo investigate factors affecting the long-term health behaviours and outcomes of headache patients and to design a risk-stratification tool.MethodsA population based observational-longitudinal cohort study using primary care electronic healthcare records from the UK Clinical Practice Research Datalink. 550,103 participants with a headache or migraine diagnosis of which 170,336 patients were identified as having recurrent headache-related events. Univariate and multivariable survival analysis was performed to determine factors influencing remission and a neural network classifier was developed.ResultsThere were almost twice as many female patients (352,330) as males (197,802). The median age at which a patient first saw their GP in males was 38 years, and in females was 37 years. Whilst age, gender and social deprivation significantly influenced the likelihood of seeing a GP, these factors had little effect on likelihood of remission from a period of recurrent headache-related events. In contrast, a comorbidity during the recurrent headache period reduced the risk of remission and increased median survival time from approximately 400-days up 1600. Increasing numbers of comorbidities progressively reduced the hazard risks for remission. The prediction models on remission within two and five years, demonstrated high precision and recall, with an F1 score of 0.795 and 0.887, respectively.InterpretationHeadache patients who suffer comorbidities have a substantively reduced likelihood of remission, highlighting an opportunity to considerably improve health outcomes in recurrent headache patients through addressing multi-morbidity more effectively. The prediction model could be used to help stratify patients most at risk of poor long-term outcomes.

BackgroundMonitoring is the mainstay of chronic kidney disease management in primary care; however, there is little evidence about the best way to do this.AimTo compare the effectiveness of estimated glomerular filtration rate (eGFR) derived from serum creatinine and serum cystatin C to predict renal function decline among those with a recent eGFR of 30–89 ml/min/1.73 m2.Design and settingObservational cohort study in UK primary care.MethodSerum 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 m2 within the previous year. The primary outcome was change in eGFR derived from serum creatinine or serum cystatin C between 6 and 24 months.ResultsAverage change in eGFR was 0.51 ml/min/1.73 m2/year when estimated by serum creatinine and −2.35 ml/min/1.73 m2/year when estimated by serum cystatin C. The c-statistic for predicting renal decline using serum creatininederived eGFR was 0.495 (95% confidence interval [CI] = 0.471 to 0.519). The equivalent c-statistic using serum cystatin C-derived eGFR was 0.497 (95% CI = 0.468 to 0.525). Similar results were obtained when restricting analyses to those aged ≥75 or 2. In those with eGFR 2, serum cystatin C-derived eGFR was more predictive than serum creatinine-derived eGFR for future decline in kidney function.ConclusionIn 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 2.

IntroductionSafety-netting in primary care is the best practice in cancer diagnosis, ensuring that patients are followed up until symptoms are explained or have resolved. Currently, clinicians use haphazard manual solutions. The ubiquitous use of electronic health records provides an opportunity to standardise safety-netting practices.A new electronic safety-netting toolkit has been introduced to provide systematic ways to track and follow up patients. We will evaluate the effectiveness of this toolkit, which is embedded in a major primary care clinical system in England:Egerton Medical Information System(EMIS)-Web.Methods and analysisWe will conduct a stepped-wedge cluster RCT in 60 general practices within the RCGP Research and Surveillance Centre (RSC) network. Groups of 10 practices will be randomised into the active phase at 2-monthly intervals over 12 months. All practices will be activated for at least 2 months. The primary outcome is the primary care interval measured as days between the first recorded symptom of cancer (within the year prior to diagnosis) and the subsequent referral to secondary care. Other outcomes include referrals rates and rates of direct access cancer investigation.Analysis of the clustered stepped-wedge design will model associations using a fixed effect for intervention condition of the cluster at each time step, a fixed effect for time and other covariates, and then include a random effect for practice and for patient to account for correlation between observations from the same centre and from the same participant.Ethics and disseminationEthical approval has been obtained from the North West—Greater Manchester West National Health Service Research Ethics Committee (REC Reference 19/NW/0692). Results will be disseminated in peer-reviewed journals and conferences, and sent to participating practices. They will be published on the University of Oxford Nuffield Department of Primary Care and RCGP RSC websites.Trial registration numberISRCTN15913081; Pre-results.

BackgroundInfluenza and influenza-like illness (ILI) place considerable burden on healthcare systems, especially during influenza epidemics and pandemics. During the 2009/10 H1N1 influenza pandemic, UK national guidelines recommended antiviral medications for patients presenting within 72 h of ILI onset. However, it is not clear whether antiviral treatment was associated with reductions in influenza-related complications.MethodsOur study population consisted of a retrospective cohort of children aged ≤17 years who presented with influenza/ILI at UK primary care practices contributing to the Clinical Practice Research Datalink during the 2009/10 pandemic. We used doubly robust inverse-probability weighted propensity scores and physician prior prescribing instrumental variable methods to estimate the causal effect of oseltamivir prescribing on influenza-related complications. Secondary outcomes were complications requiring intervention, pneumonia, pneumonia or hospitalisation, influenza-related hospitalisation and all-cause hospitalisation.ResultsWe included 16 162 children, of whom 4028 (24.9%) were prescribed oseltamivir, and 753 (4.7%) had recorded complications. Under propensity score analyses oseltamivir prescriptions were associated with reduced influenza-related complications (risk difference (RD) −0.015, 95% CI −0.022–−0.008), complications requiring further intervention, pneumonia, pneumonia or hospitalisation and influenza-related hospitalisation, but not all-cause hospitalisation. Adjusted instrumental variable analyses estimated reduced influenza-related complications (RD −0.032, 95% CI −0.051–−0.013), pneumonia or hospitalisation, all-cause and influenza-related hospitalisations.ConclusionsBased on causal inference analyses of observational data, oseltamivir treatment in children with influenza/ILI was associated with a small but statistically significant reduction in influenza-related complications during an influenza pandemic.

© 2019 Nicholson et al. Purpose: To use recorded weight values to internally validate weight status and weight change coding in the primary care Electronic Health Record (EHR). Patients and methods: We included adult patients with weight-related Read codes recorded in the UK’s Clinical Practice Research Datalink EHR between 2000 and 2017. Weight status codes were compared to weight values recorded on the same day and positive predictive values (PPVs) were calculated for commonly used codes. Weight change codes were validated using three methods: the percentage (%) difference in kilograms at the time of the code and 1) the previous weight measurement, 2) the weight predicted using linear regression, and 3) the historic mean weight. Weight change codes were validated if estimates were consistent across two out of three methods. Results: A total of 8,108,481 weight codes were recorded in 1,000,002 patients’ EHR. Twice as many were recorded in females (n=5,208,593, 64%). The mean body mass index for “over-weight” codes ranged from 31.9 kg/m 2 to 46.9 kg/m 2 and from 17.4 kg/m 2 to 19.2 kg/m 2 for “underweight” codes. PPVs for the most commonly used weight status codes ranged from 81.3% (80%–82.5%) to 99.3% (99.2%–99.4%). Across the estimation methods, and using only validated weight change codes, mean weight loss ranged from – 5.2% (SD 5.8%) to –7.9% (SD 7.3%) and mean weight gain from 4.2 % (SD 5.5%) to 7.9 % (SD 8.2%). The previous and predicted weight methods were most consistent. Conclusion: We have developed an internationally applicable methodology to internally validate weight-related EHR coding by using available weight measurement data. We demonstrate the UK Read codes that can be confidently used to classify weight status and weight change in the absence of weight values. We provide the first evidence from primary care that a Read code for unexpected weight loss represents a mean loss of ≥ 5 % in a 6-month period, which was broadly consistent across age groups and gender.

BackgroundDirect access (DA) testing allows GPs to refer patients for investigation without consulting a specialist. The aim is to reduce waiting time for investigations and unnecessary appointments, enabling treatment to begin without delay.AimTo establish the proportion of patients diagnosed with cancer and other diseases through DA testing, time to diagnosis, and suitability of DA investigations.Design and settingSystematic review assessing the effectiveness of GP DA testing in adults.MethodMEDLINE, Embase, and the Cochrane Library were searched. Where possible, study data were pooled and analysed quantitatively. Where this was not possible, the data are presented narratively.ResultsThe authors identified 60 papers that met pre-specified inclusion criteria. Most studies were carried out in the UK and were judged to be of poor quality. The authors found no significant difference in the pooled cancer conversion rate between GP DA referrals and patients who first consulted a specialist for any test, except gastroscopy. There were also no significant differences in the proportions of patients receiving any non-cancer diagnosis. Referrals for testing were deemed appropriate in 66.4% of those coming from GPs, and in 80.9% of those from consultants; this difference was not significant. The time from referral to testing was significantly shorter for patients referred for DA tests. Patient and GP satisfaction with DA testing was consistently high.ConclusionGP DA testing performs as well as, and on some measures better than, consultant triaged testing on measures of disease detection, appropriateness of referrals, interval from referral to testing, and patient and GP satisfaction.

© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Earlier detection of colorectal cancer greatly improves prognosis, largely through surgical excision of neoplastic polyps. These include benign adenomas which can transform over time to malignant adenocarcinomas. This progression may be associated with changes in full blood count indices. An existing risk algorithm derived in Israel stratifies individuals according to colorectal cancer risk using full blood count data, but has not been validated in the UK. We undertook a retrospective analysis using the Clinical Practice Research Datalink. Patients aged over 40 with full blood count data were risk-stratified and followed up for a diagnosis of colorectal cancer over a range of time intervals. The primary outcome was the area under the receiver operating characteristic curve for the 18–24-month interval. We also undertook a case–control analysis (matching for age, sex, and year of risk score), and a cohort study of patients undergoing full blood count testing during 2012, to estimate predictive values. We included 2,550,119 patients. The area under the curve for the 18–24-month interval was 0.776 [95% confidence interval (CI): 0.771, 0.781]. Performance improves as the time interval reduces. The area under the curve for the age-matched case–control analysis was 0.583 [0.574, 0.591]. For the population risk-scored in 2012, the positive predictive value at 99.5% specificity was 8.8% with negative predictive value 99.6%. The algorithm offers an additional means of identifying risk of colorectal cancer, and could support other approaches to early detection, including screening and active case finding.

Background: There was excess mortality from the first wave of coronavirus 2019 infection (COVID-19), which mainly affected older people. To mitigate risk, the UK government recommended ‘shielding’ of vulnerable people through self-isolation for 12 weeks. We investigated the impact of primary care-reinforced shielding advice on all-cause mortality. Methods: We conducted a retrospective cohort study using a nationally representative English primary care database. We compare people aged >=40years who were recorded as being advised to shield using a fixed ratio of 1:1, matching (a mixture of exact and propensity score matching) to people with the same diagnoses not advised to shield (n=77,360 per group). Time-to-death was compared using Cox regression, reporting the hazard ratio (HR) of mortality between groups. A sensitivity analysis compared exact matched cohorts (n=24,752 shielded, n=61,566 exact matches). Findings: Over the follow-up period, we found a time-varying HR of mortality between groups. In the first 21 days, the mortality risk in people shielding was half those not (HR=0.50, 95%CI:0.41-0.59. p

BackgroundSafety netting is a diagnostic strategy that involves monitoring patients with symptoms possibly indicative of serious illness, such as cancer, until they are resolved. Optimising safety-netting practice in primary care has been proposed to improve quality of care and clinical outcomes. Introducing guidelines is a potential means to achieve this.AimTo seek the insight of frontline GPs regarding proposed safety-netting guidelines for suspected cancer in UK primary care.Design and settingA qualitative interview study with 25 GPs practising in Oxfordshire, UK.MethodTranscripts from semi-structured interviews were analysed thematically by a multidisciplinary research team using a mind-mapping approach.ResultsGPs were supportive of initiatives to optimise safety netting. Guidelines on establishing who has responsibility for follow-up, keeping patient details up to date, and ensuring test result review is conducted by someone with knowledge of cancer guidelines were already being followed. Sharing diagnostic uncertainty and ensuring an up-to-date understanding of guidelines were only partially implemented. Neither informing patients of all (including negative) test results nor ensuring recurrent unexplained symptoms are always flagged and referred were considered feasible. The lack of detail, for example, the expected duration of symptoms, caused some concern. Overall, doubts were expressed about the feasibility of the guidelines given the time, recruitment, and resource challenges faced in UK primary care.ConclusionGPs expressed general support for safety netting, yet were unconvinced that key elements of the guidelines were feasible, especially in the context of pressures on general practice staffing and time.

© 2020 The British Association of Oral and Maxillofacial Surgeons Oral cancer is referred to specialists by both general practitioners (GPs) and dentists, with varying proportions reported in different studies. However, some have noted that dentists more commonly refer oral cancer in the absence of patient-perceived symptoms and may refer at an earlier stage. Unfortunately, approximately half the UK adult population do not receive regular dental care. We have conducted a systematic review of studies that compare GPs and dentists in the referral of oral cancer and have focused on three aspects: the proportion of diagnosed oral cancers, stage on presentation, and delay. Searches of the databases Medline, Embase, Scopus, Google Scholar, Web of Science, and CINAHL, together with additional searches of reference lists, authors, and conference proceedings, found 22 studies from 10 countries, which included a total of 4953 oral cancers. The percentage of medical referrals ranged from 13% to 86%; dental referrals ranged from 15% to 80%. Random-effects meta-analysis indicated a combined relative risk of medical referral to dental referral of 1.36 (95% CI: 0.99 to 1.86). For UK-based studies, the relative risk was also 1.36 (95% CI: 1.05 to 1.76). There was considerable heterogeneity for all studies and for a subgroup of UK studies: I296.4% (95% CI 95.4 to 97.1) and 81.0% (95% CI 63.3 to 90.1), respectively. Several studies showed a lower stage for dentally-referred cancers; the combined risk for dentists and GPs referring early (stages 1 and 2) disease was 1.37 (95% CI: 1.17 to 1.60), and one cause may be the much higher number of cases referred by dentists in the absence of symptoms. No studies showed a significant difference in delay. Oral cancer is referred by both GPs and dentists, typically about 50% and 40%, respectively, although there is a wide range, probably depending on local circumstances. Both groups require skills in oral examination, recognition of lesions, and knowledge of the risk factors. Effectively, regular dental attenders are a select group that is regularly screened for oral cancer, and it is likely that screening is not delivered to those with the highest risk. We suggest that further work is required on how to access high-risk individuals both for possible screening and preventive interventions.

ObjectiveTo explore patients’ and General Practitioners' (GPs) accounts of how responsibility for follow-up was perceived and shared in their experiences of cancer safety netting occurring within the past 6 months.DesignIn-depth interviews were recorded and transcribed verbatim. Data were analysed through an abductive process, exploring anticipated and emergent themes. Conceptualisations of ‘responsibility’ were explored by drawing on atransactionaltointerdependentcontinuum drawing from the shared decision-making literature.Settings and participantsA purposive sample of 25 qualified GPs and 23 adult patients in Oxfordshire, UK.ResultsThe transactional sharing approach involves responsibility being passed from GP to patient. Patients expected and were willing to accept responsibility in this way as long as they received clear guidance from their GP and had capacity. In interdependent sharing, GPs principally aimed to reach consensus and share responsibility with the patient by explaining their rationale, uncertainty or by stressing the potential seriousness of the situation. Patients sharing this responsibility could be put at risk if no follow-up or timeframe was suggested, they had inadequate information, were falsely reassured or their concerns were not addressed at re-consultation.ConclusionGPs and patients exchange and share responsibility using a combination of transactional and interdependent styles, tailoring information based on patient characteristics and each party’s level of concern. Clear action plans (written where necessary) at the end of every consultation would help patients decide when to re-consult. Further research should investigate how responsibility is shared within and outside the consultation, within primary care teams and with specialist services.

ObjectiveTo evaluate the effects of drug interventions that may modify the progression of chronic kidney disease (CKD) in adults with CKD stages 3 and 4.DesignSystematic review and meta-analysis.MethodsSearching MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, International Clinical Trials Registry Platform, Health Technology Assessment, Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index and Clinical Trials Register, from March 1999 to July 2018, we identified randomised controlled trials (RCTs) of drugs for hypertension, lipid modification, glycaemic control and sodium bicarbonate, compared with placebo, no drug or a drug from another class, in ≥40 adults with CKD stages 3 and/or 4, with at least 2 years of follow-up and reporting renal function (primary outcome), proteinuria, adverse events, maintenance dialysis, transplantation, cardiovascular events, cardiovascular mortality or all-cause mortality. Two reviewers independently screened citations and extracted data. For continuous outcomes, we used the ratio of means (ROM) at the end of the trial in random-effects meta-analyses. We assessed methodological quality with the Cochrane Risk of Bias Tool and confidence in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.ResultsWe included 35 RCTs and over 51 000 patients. Data were limited, and heterogeneity varied. Final renal function (estimated glomerular filtration rate) was 6% higher in those taking glycaemic control drugs (ROM 1.06, 95% CI 1.02 to 1.10, I2=0%, low GRADE confidence) and 4% higher in those taking lipid-modifying drugs (ROM 1.04, 95% CI 1.00 to 1.08, I2=88%, very low GRADE confidence). For RCTs of antihypertensive drugs, there were no significant differences in renal function. Treatment with lipid-modifying drugs led to a 36% reduction in cardiovascular disease and 26% reduction in all-cause mortality.ConclusionsGlycaemic control and lipid-modifying drugs may slow the progression of CKD, but we found no pooled evidence of benefit nor harm from antihypertensive drugs. However, given the data limitations, further research is needed to confirm these findings.PROSPERO registration numberCRD42015017501.

BackgroundChildhood antibiotic exposure has important clinically relevant implications. These include disruption to the microbiome, antibiotic resistance, and clinical workload manifesting as treatment ‘failure’.AimTo examine the relationship between the number of antibiotic courses prescribed to preschool children for acute respiratory tract infections (RTI), in the preceding year, and subsequent RTIs that failed to respond to antibiotic treatment (‘response failures’).Design and settingA cohort study using UK primary care data from the Clinical Practice Research Datalink, 2009 to 2016.MethodChildren aged 12 to 60 months (1 to 5 years) who were prescribed an antibiotic for an acute RTI (upper and lower RTI or otitis media) were included. One random index antibiotic course for RTI per child was selected. Exposure was the number of antibiotic prescriptions for acute RTI up to 12 months before the index antibiotic prescription. The outcome was ‘response failure’ up to 14 days after index antibiotic prescription, defined as: subsequent antibiotic prescription; referral; hospital admission; death; or emergency department attendance within 3 days. The authors used logistic regression models to estimate the odds between antibiotic exposure and response failure.ResultsOut of 114 329 children who were prescribed an antibiotic course for acute RTI, children who received ≥2 antibiotic courses for acute RTIs in the preceding year had greater odds of response failure; one antibiotic course: adjusted odds ratio (OR) 1.03 (95% confidence interval [CI] = 0.88 to 1.21), P = 0.67, n = 230 children; ≥2 antibiotic courses: adjusted OR 1.32 (CI = 1.04 to 1.66), P = 0.02, n = 97.ConclusionChildhood antibiotic exposure for acute RTI may be a good predictor for subsequent response failure (but not necessarily because of antibiotic treatment failure). Further research is needed to improve understanding of the mechanisms underlying response failure.

Background Excess weight and unexpected weight loss are associated with multiple disease states and increased morbidity and mortality, but weight measurement is not routine in many primary care settings. The aim of this study was to characterise who has had their weight recorded in UK primary care, how frequently, by whom and in relation to which clinical events, symptoms and diagnoses. Methods A longitudinal analysis of UK primary care electronic health records (EHR) data from 2000 to 2017. Descriptive statistics were used to summarise weight recording in terms of patient sociodemographic characteristics, health professional encounters, clinical events, symptoms and diagnoses. Negative binomial regression was used to model the likelihood of having a weight record each year, and Cox regression to the likelihood of repeated weight recording. Results A total of 14,049,871 weight records were identified in the EHR of 4,918,746 patients during the study period, representing 26,998,591 person-years of observation. Around a third of patients had a weight record each year. Forty-nine percent of weight records were repeated within a year with an average time to a repeat weight record of 1.92 years. Weight records were most often taken by nursing staff (38–42%) and GPs (37–39%) as part of a routine clinical care, such as chronic disease reviews (16%), medication reviews (6–8%) and health checks (6–7%), or were associated with consultations for contraception (5–8%), respiratory disease (5%) and obesity (1%). Patient characteristics independently associated with an increased likelihood of weight recording were as follows: female sex, younger and older adults, non-drinkers, ex-smokers, low or high BMI, being more deprived, diagnosed with a greater number of comorbidities and consulting more frequently. The effect of policy-level incentives to record weight did not appear to be sustained after they were removed. Conclusion Weight recording is not a routine activity in UK primary care. It is recorded for around a third of patients each year and is repeated on average every 2 years for these patients. It is more common in females with higher BMI and in those with comorbidity. Incentive payments and their removal appear to be associated with increases and decreases in weight recording.

BackgroundGUIDE-IT, the largest trial to date, published in August 2017, evaluating the effectiveness of natriuretic peptide (NP)-guided treatment of heart failure (HF), was stopped early for futility on a composite outcome. However, the reported effect sizes on individual outcomes of all-cause mortality and HF admissions are potentially clinically relevant.ObjectiveThis systematic review and meta-analysis aims to combine all available trial level evidence to determine if NP-guided treatment of HF reduces all-cause mortality and HF admissions in patients with HF.Study selectionEight databases, no language restrictions, up to November 2017 were searched for all randomised controlled trials comparing NP-guided treatment versus clinical assessment alone in adult patients with HF. No language restrictions were applied. Publications were independently double screened and extracted. Fixed-effect meta-analyses were conducted.Findings89 papers were included, reporting 19 trials (4554 participants), average ages 62–80 years. Pooled risk ratio estimates for all-cause mortality (16 trials, 4063 participants) were 0.87, 95% CI 0.77 to 0.99 and 0.80, 95% CI 0.72 to 0.89 for HF admissions (11 trials, 2822 participants). Sensitivity analyses, restricted to low risk of bias, produced similar estimates, but were no longer statistically significant.ConclusionsConsidering all the evidence to date, the pooled effects suggest that NP-guided treatment is beneficial in reducing HF admissions and all-cause mortality. However, there is still insufficient high-quality evidence to make definitive recommendations on the use of NP-guided treatment in clinical practice.Trial registration numberSystematic Review Cochrane Database Number: CD008966.

Objectives Previous research shows that the terminology ‘chronic kidney disease’ (CKD) is problematic for both patients and general practitioners, arguably because it represents an ageing process rather than a disease. We have previously proposed an alternative terminology ‘kidney age’ to supersede the terminology of CKD stages 2, 3a, 3b and 4. We aim to develop a communication tool that can be used to discuss declining kidney function with patients without using the terminology of ‘disease’. Method We used electronic health record data from UK primary care to design a prototype communication aid: a table and explanatory text showing how eGFR values map to bands of ‘kidney age’, and the increasing CVD risk at each band of kidney age. The design and content were refined iteratively in consultation with patient-public involvement representatives. UK general practitioners were then interviewed about the proposed design and content. Results Interviews are ongoing but results to date suggest that GPs would welcome ‘kidney age’ terminology and our communication tool, possibly modified, as a potential intervention. Conclusions A web-based version of the communication aid is currently under development, that can be tested as an intervention in a future parallel-group trial.

AIMS/HYPOTHESIS: Observational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs). METHODS: RCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available; cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I (2)statistics for heterogeneity were calculated by fixed effects meta-analysis. RESULTS: Of 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials. CONCLUSIONS/INTERPRETATION: Meta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality.

Background The ‘two-week rule’ (TWR) fast-track cancer referral system for head and neck cancers was introduced by the UK government in 2000, to facilitate earlier diagnosis. However, little work has compared stage on diagnosis of cancer before and after the implementation of the system. Objectives • Describe the presentation of oral cancer in Merseyside from 1992 to 2012. • To evaluate whether stage on presentation has improved after the introduction of the TWR using data from a clinical database in Merseyside 1992–2012. • To assess the relationship between stage on presentation and social deprivation 1992–2012. • To assess the change in presentation for different sites within the oral cavity. Method and setting Patients were identified using the Aintree (Liverpool) head and neck oncology database, containing all diagnoses of oral squamous cell carcinoma (SCC) between 1992 – 2012. Cancers were clinically staged using the American Joint Committee on Cancer (AJCC) stage groupings and divided into ‘early’ (stage 1 and 2) and ‘late’ (stage 3 and 4). Index of Multiple Deprivation (IMD) 2004 data were derived from patient postcodes. Appropriate regression analyses were undertaken. Results 1485 consecutive patients diagnosed were studied. Median (IQR) age was 63 (55–73) years and 61% were male. 36% of cancers were located on anterior 2/3rds tongue, 30% floor of mouth, and 34% elsewhere. ‘Late’ tumour presentation was 52% (95%CI 46.8–56.4%) for 1992–2000, and 44% (95%CI 41.4–47.5%) for 2001–2012 (P = 0.01). Joinpoint regression analysis of ‘late’ presentation indicated a steady fall 1992–2012, at an annual percentage decrease of 1.27% (95% CI −2.3 to −0.2). No statistically significant change in trend was identified either overall or within deprivation groups following the TWR. For patients in ‘more deprived’ neighbourhoods, ‘late’ tumour presentation was: 56% and 47%; in ‘less deprived’ areas: 48% and 42%, before and after the introduction of the TWR, respectively. Year of diagnosis, tumour site and IMD2004 were significantly associated with ‘late’ presentation, and location of tumour was also associated with time period and IMD2004. Main conclusions Stage on presentation improved between 1992–2012. Joinpoint analysis showed no significant change in trend following the introduction of the TWR. The rate of improvement was highest for most deprived; nevertheless, deprivation inequality persists and this should be a focus of further initiatives and research.

Background Primary care workload is high and increasing in the United Kingdom. We sought to examine the association between rates of primary care consultation and outcomes in England. Methods Cross sectional observational study of routine electronic health care records in 283 practices from the Clinical Practice Research Datalink from April 2013 to March 2014. Outcomes included mortality rate, hospital admission rate, Quality and Outcomes Framework (QOF) performance and patient satisfaction. Relationships between consultation rates (with a general practitioner (GP) or nurse) and outcomes were investigated using negative binomial and ordinal logistic regression models. Results Rates of GP and nurse consultation (per patient person-year) were not associated with mortality or hospital admission rates: mortality incidence rate ratio (IRR) per unit change in GP/ nurse consultation rate = 1.01, 95% CI [0.98 to 1.04]/ 0.97, 95% CI [0.93 to 1.02]; hospital admission IRR per unit change in GP/ nurse consultation rate = 1.02, 95% CI [0.99 to 1.04]/ 0.98, 95% CI [0.94 to 1.032]. Higher rates of nurse but not GP consultation were associated with higher QOF achievement: OR = 1.91, 95% CI [1.39 to 2.62] per unit change in nurse consultation rate vs. OR = 1.04, 95% CI [0.87 to 1.24] per unit change in GP consultation rate. The association between the rates of GP/ nurse consultations and patient satisfaction was mixed. Conclusion There are few associations between primary care consultation rates and outcomes. Previously identified demographic and staffing factors, rather than practice workload, appear to have the strongest relationships with mortality, admissions, performance and satisfaction. Studies with more detailed patient-level data would be required to explore these findings further. Electronic supplementary material The online version of this article (10.1186/s12913-019-4036-y) contains supplementary material, which is available to authorized users.

Background The UK’s National Health Service (NHS) is currently subject to unprecedented financial strain. The identification of unnecessary healthcare resource use has been suggested to reduce spending. However, there is little very research quantifying wasteful test use, despite the £3 billion annual expenditure. Geographical variation has been suggested as one metric in which to quantify inappropriate use. We set out to identify tests ordered from UK primary care that are subject to the greatest between-practice variation in their use. Methods We used data from 444 general practices within the Clinical Practice Research Datalink to calculate a coefficient of variation (CoV) for the ordering of 44 specific tests from UK general practices. The coefficient of variation was calculated after adjusting for differences between practice populations. We also determined the tests that had both a higher-than-average CoV and a higher-than-average rate of use. Results In total, 16,496,218 tests were ordered for 4,078,091 patients over 3,311,050 person-years from April 1, 2015, to March 31, 2016. The tests subject to the greatest variation were drug monitoring 158% (95%CI 153 to 163%), urine microalbumin (52% (95%CI 49.9 to 53.2%)), pelvic CT (51% (95%CI 50 to 53%)) and Pap smear (49% (95%CI 48 to 51%). Seven tests were classified as high variability and high rate (clotting, vitamin D, urine albumin, prostate-specific antigen (PSA), bone profile, urine MCS and C-reactive protein (CRP)). Conclusions There are wide variations in the use of common tests, which is unlikely to be explained by clinical indications. Since £3 billion annually are spent on tests, this represents considerable variation in the use of resources and inefficient management in the NHS. Our results can be of value to policy makers, researchers, patients and clinicians as the NHS strives towards identifying overuse and underuse of tests. Electronic supplementary material The online version of this article (10.1186/s12916-018-1217-1) contains supplementary material, which is available to authorized users.

One-year survival after head and neck cancer in England has been reported to be worse than that in Europe, despite five-year conditional survival being similar, which implies that patients present later in England. One country with better rates is The Netherlands. There are many possible causes, one of which may be the system of referral from primary to secondary care. We have compared the views of secondary care specialists in the two countries about their systems for referral, and identified aspects that might have an impact on outcomes. We organised semistructured qualitative interviews of surgical specialists in head and neck cancer in England and The Netherlands (n = 12 in each). The most common theme was communication between primary care and specialists. Surgeons in England identified this as the aspect most lacking under the English “two-week” rule, while Dutch specialists felt that the good communication in their system was one of its best points. Other themes included the educational needs of primary care practitioners, criticism of “tick box” referrals in England, and too many patients referred who do not have cancer. Overall, specialists in both countries identified good aspects of their respective referral systems, but those in England felt strongly that the “two-week” rule/NICE guidance system could be improved with better direct communication between primary and secondary care, which might improve the speed and quality of referrals, reduce unnecessary ones, and assist in educating primary care physicians. It is not clear whether such improvements would improve survival, but further research and piloting of such a system should be considered in England.

Background Analgesics are used most frequently in fatal and non-fatal medicinal self-poisonings. Knowledge about their relative toxicity in overdose is important for clinicians and regulatory agencies. Methods Using data for 2005–2012 we investigated case fatality (number of suicides relative to number of non-fatal self-poisonings) of paracetamol, aspirin, codeine, dihydrocodeine, tramadol, paracetamol with codeine (co-codamol), paracetamol with dihydrocodeine (co-dydramol), ibuprofen and co-proxamol (paracetamol plus dextropropoxyphene; withdrawn in the UK in 2008 due to high toxicity). Data on suicides obtained from the Office for National Statistics and on non-fatal self-poisonings from the Multicentre Study of Self-harm in England. Case fatality was estimated for each drug, using paracetamol as the reference category. Results Compared to paracetamol and based on single drug deaths the case fatality index of dihydrocodeine was considerably elevated (odds ratio (OR) 12.81, 95% Confidence Interval (CI) 10.19–16.12). Case fatality indices for tramadol (OR 4.05, 95% CI 3.38–4.85) and codeine (OR 2.21, 95% CI 1.81–2.70) were also significantly higher than for paracetamol. The results when multiple drug deaths were included produced similar results. The relative toxicity of co-proxamol far exceeded that of the other analgesics. Limitations Data on fatal self-poisonings were based on national data, whereas those for non-fatal poisonings were based on local data. Conclusions Dihydrocodeine and tramadol are particularly toxic in overdose and codeine is also relatively toxic. They should be prescribed with caution, particularly to individuals at risk of self-harm.

Objectives To assess the temporal change in test use in UK primary care and to identify tests with the greatest increase in use. Design Retrospective cohort study. Setting UK primary care. Participants All patients registered to UK General Practices in the Clinical Practice Research Datalink, 2000/1 to 2015/16. Main outcome measures Temporal trends in test use, and crude and age and sex standardised rates of total test use and of 44 specific tests. Results 262 974 099 tests were analysed over 71 436 331 person years. Age and sex adjusted use increased by 8.5% annually (95% confidence interval 7.6% to 9.4%); from 14 869 tests per 10 000 person years in 2000/1 to 49 267 in 2015/16, a 3.3-fold increase. Patients in 2015/16 had on average five tests per year, compared with 1.5 in 2000/1. Test use also increased statistically significantly across all age groups, in both sexes, across all test types (laboratory, imaging, and miscellaneous), and 40 of the 44 tests that were studied specifically. Conclusion Total test use has increased markedly over time, in both sexes, and across all age groups, test types (laboratory, imaging, and miscellaneous) and for 40 of 44 tests specifically studied. Of the patients who underwent at least one test annually, the proportion who had more than one test increased significantly over time.

Purpose Overlooking other medical conditions during cancer treatment and follow-up could result in excess morbidity and mortality, thereby undermining gains associated with early detection and improved treatment of cancer. We compared the quality of care for diabetes patients subsequently diagnosed with breast, colorectal, or prostate cancer to matched, diabetic non-cancer controls. Methods Longitudinal cohort study using primary care records from the Clinical Practice Research Datalink, United Kingdom. Patients with pre-existing diabetes were followed for up to 5 years after cancer diagnosis, or after an assigned index date (non-cancer controls). Quality of diabetes care was estimated based on Quality and Outcomes Framework indicators. Mixed effects logistic regression analyses were used to compare the unadjusted and adjusted odds of meeting quality measures between cancer patients and controls, overall and stratified by type of cancer. Results 3382 cancer patients and 11,135 controls contributed 44,507 person-years of follow-up. In adjusted analyses, cancer patients were less likely to meet five of 14 quality measures, including: total cholesterol ≤ 5 mmol/L (odds ratio [OR] = 0.82; 95% confidence interval [CI], 0.75–0.90); glycosylated hemoglobin ≤ 59 mmol/mol (adjusted OR = 0.77; 95% CI, 0.70–0.85); and albumin creatinine ratio testing (adjusted OR = 0.83; 95% CI, 0.75–0.91). However, cancer patients were as likely as their matched controls to meet quality measures for other diabetes services, including retinal screening, foot examination, and dietary review. Conclusions Although in the short-term, cancer patients were less likely to achieve target thresholds for cholesterol and HbA1c, they continued to receive high-quality diabetes primary care throughout 5 years post diagnosis. Implications for Cancer Survivors These findings are important for cancer survivors with pre-existing diabetes because they indicate that high-quality diabetes care is maintained throughout the continuum of cancer diagnosis, treatment, and follow-up. Electronic supplementary material The online version of this article (10.1007/s11764-018-0717-5) contains supplementary material, which is available to authorized users.

Background Several studies have investigated the effect of socioeconomic deprivation on cardiovascular disease (CVD) and diabetes; less is known about its effect on chronic kidney disease (CKD). We aimed to measure the association between deprivation, CKD Stages 4–5 and end-stage renal disease (ESRD) in a general population sample. Methods This observational study examined 1 405 016 participants from the English Clinical Practice Research Datalink (2000–14), linked to hospital discharge data and death certification. Deprivation was assessed according to the participant’s postcode. Cox models were used to estimate hazard ratios (HRs) for CKD Stages 4–5 and ESRD, adjusting for age and sex, and additionally for smoking status, body mass index, diabetes, systolic blood pressure, prior CVD and estimated glomerular filtration rate (eGFR) at baseline. Results During 7.5 years of median follow-up, 11 490 individuals developed CKD Stages 4–5 and 1068 initiated ESRD. After adjustment for age and sex, the HRs and confidence interval (CI) comparing those in the 20% most deprived of the population to the 20% least deprived were 1.76 (95% CI 1.68–1.84) and 1.82 (95% CI 1.56–2.12) for CKD Stages 4–5 and ESRD, respectively. Further adjustment for known risk factors and eGFR substantially attenuated these HRs. Adding our results to all known cohort studies produced a pooled relative risk of 1.61 (95% CI 1.42–1.83) for ESRD, for comparisons between highest to lowest categories of deprivation. Conclusion Socioeconomic deprivation is independently associated with an increased hazard of CKD Stages 4–5 and ESRD, but in large part may be mediated by known risk factors.

Hypertensive disorders during pregnancy result in substantial maternal morbidity and are a leading cause of maternal deaths worldwide. Self-monitoring of blood pressure (BP) might improve the detection and management of hypertensive disorders of pregnancy, but few data are available, including regarding appropriate thresholds. This systematic review and individual patient data analysis aimed to assess the current evidence on differences between clinic and self-monitored BP through pregnancy. MEDLINE and 10 other electronic databases were searched for articles published up to and including July 2016 using a strategy designed to capture all the literature on self-monitoring of BP during pregnancy. Investigators of included studies were contacted requesting individual patient data: self-monitored and clinic BP and demographic data. Twenty-one studies that utilized self-monitoring of BP during pregnancy were identified. Individual patient data from self-monitored and clinic readings were available from 7 plus 1 unpublished articles (8 studies; n=758) and 2 further studies published summary data. Analysis revealed a mean self-monitoring clinic difference of ≤1.2 mm Hg systolic BP throughout pregnancy although there was significant heterogeneity (difference in means, I 2 >80% throughout pregnancy). Although the overall population difference was small, levels of white coat hypertension were high, particularly toward the end of pregnancy. The available literature includes no evidence of a systematic difference between self and clinic readings, suggesting that appropriate treatment and diagnostic thresholds for self-monitoring during pregnancy would be equivalent to standard clinic thresholds.

Objectives: To assess the diagnostic accuracy of point-of-care natriuretic peptide tests in patients with chronic heart failure, with a particular focus on the ambulatory care setting. Design: Systematic review and diagnostic meta-analysis. Data sources: Ovid MEDLINE, the Cochrane Register of Controlled Trials, the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Embase, Health Technology Assessment, Science Citation Index and Conference Proceedings Citation Index until 31 March 2017. Study selection: Eligible studies evaluated point-of-care natriuretic peptide testing (B type natriuretic peptide [BNP] or N-terminal pro-brain natriuretic peptide [NT-proBNP]) against any relevant reference standard, echocardiography, clinical examination or combinations of these, in humans. Studies were excluded if insufficient data was reported to construct 2x2 tables. No language restrictions were applied. Results: 42 publications of 39 individual studies met our inclusion criteria and 40 publications of 37 studies were included in our analysis. Of these 37 studies, 30 evaluated BNP point-of-care testing, and 7 evaluated NT-proBNP testing. Fifteen studies were carried out in ambulatory care settings with low prevalence populations. Five studies were undertaken in primary care. At thresholds >100 pg/mL sensitivity of BNP, measured with the Triage, was generally high and 0.95 (95% CI 0.90 to 0.98) at 100 pg/mL. At lower thresholds of Conclusions: Given the general lack of studies performed in primary care, the paucity of NT-proBNP data and potential methodological limitations in these studies, there is a need for large-scale trials in primary care, to assess the role of point-of-care natriuretic peptide testing and clarify appropriate thresholds to improve care of patients with suspected or chronic heart failure.

Primary care clinicians have a central role in managing influenza/influenza-like illness (ILI) during influenza pandemics. This study identifies risk factors for influenza-related complications in children presenting with influenza/ILI in primary care. We conducted a cohort study using routinely collected linked data from the Clinical Practice Research Datalink on children aged 17 years and younger who presented with influenza/ILI during the 2009/10 pandemic. We calculated odds ratios (ORs) for potential risk factors in relation to influenza-related complications, complications requiring intervention, pneumonia, all-cause hospitalisation and hospitalisation due to influenza-related complications within 30 days of presentation. Analyses were adjusted for potential confounders including age, vaccination and socio-economic deprivation. Asthma was a risk factor for influenza-related complications (adjusted OR 1.48, 95% confidence interval (CI) 1.21–1.80, P < 0.001), complications requiring intervention (adjusted OR 1.44, 95% CI 1.11–1.88; P = 0.007), pneumonia (adjusted OR 1.64, 95% CI 1.07–2.51, P = 0.024) and hospitalisation due to influenza-related complications (adjusted OR 2.46, 95% CI 1.09–5.56, P = 0.031). Neurological conditions were risk factors for all-cause hospitalisation (adjusted OR 4.25, 95% CI 1.50–12.07, P = 0.007) but not influenza-related complications (adjusted OR 1.46, 95% CI 0.83–2.56, P = 0.189). Community-based early interventions to prevent influenza-related clinical deterioration should therefore be primarily targeted at children with asthma and neurological conditions.

AimTo identify the key components of natriuretic peptide (NP)-guided treatment interventions which reduced hospitalisation in patients with heart failure (HF).Methods and resultsWe extracted detailed information on the components of interventions from studies of NP-guided treatment of HF identified in a previous systematic review. We used meta-regression techniques to assess univariate associations between components and the strength of the reduction in HF hospitalisations and all-cause mortality. A Bayesian meta-analysis approach was used to re-estimate study-level effects in order to identify the study with the most effective NP-guided monitoring intervention. Finally, we examined the intervention options common to the studies in which the 95% credible interval excluded no effect. We identified eight components of NP-guided treatment from ten studies. Univariate comparisons produced mainly equivocal results, but single trial choice and common components analysis led to similar conclusions. Using a predefined treatment protocol, setting a stringent NP target (N-terminal pro-B-type natriuretic peptide of 1000 pg/mL or B-type natriuretic peptide 100 pg/mL) and including a relative targetwere potential key components to reducing HF hospitalisations using NP-guided therapy.ConclusionThis analysis provides a description of the key components of NP-guided treatment which could help policy makers develop specific recommendations for HF management. Our research suggests that NP-guided interventions could be simplified, but more research in relevant health settings, such as primary care, is required.

Commentary on : Felker GM, Anstrom KJ, Adams KF, et al . Effect of natriuretic peptide-guided therapy on hospitalisation or cardiovascular mortality in high-risk patients with heart failure and reduced ejection fraction: a randomized clinical trial. JAMA 2017;318:713–720. Natriuretic peptides (NPs), a collective term for B-type natriuretic peptide (BNP) and N(or amino)-terminal pro-B-type natriuretic peptide (NT-proBNP), are released by the myocardium in response to pressure or fluid overload. In patients with heart failure (HF) the NP levels are raised. NP testing is currently used in diagnosis and prognosis, but its role in guiding HF treatment remains uncertain. The guidelines do not currently recommend NP-guided treatment. Previous clinical trials and meta-analyses have researched NP-guided treatment with mixed results.1–6 Felker et al , in the Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study, aimed to …

Background: Unexpected weight loss is a symptom of serious disease in primary care, for example between 1 in 200 and 1 in 30 patients with unexpected weight loss go on to develop cancer. However, it remains unclear how and when General Practitioners (GPs) should investigate unexpected weight loss. Without clarification, GPs may wait too long before referring (choosing to watch and wait and potentially missing a diagnosis) or not long enough (overburdening hospital services and exposing patients to the risks of investigation). The overall aim of this study is to provide the evidence necessary to allow GPs to more effectively manage patients with unexpected weight loss. Methods: A retrospective cohort analysis of UK Clinical Practice Research Datalink (CPRD) data to: 1) describe how often in UK primary care the symptom of reported weight loss is coded, when weight is measured, and how GPs respond to a patient attending with unexpected weight loss; 2) identify the predictive value of recorded weight loss for cancer and serious disease in primary care by comparing the incidence of cancer and serious disease over time in those with and without a weight loss code, using cumulative incidence plots to compare outcomes between subgroups and Cox regression to explore and adjust for covariates. Preliminary work in CPRD estimates that weight loss as a symptom is recorded for approximately 148,000 eligible patients >18 years, and is distributed evenly across decades of age, providing adequate statistical power and precision in relation to cancer overall and common cancers individually. Further stratification by cancer stage will be attempted but may not be possible as not all practices within CPRD are eligible for cancer registry linkage and staging information is often incomplete. The feasibility of using multiple imputation to address missing covariate values will be explored. Discussion: This will be the largest reported retrospective cohort of primary care patients with weight measurements and unexpected weight loss codes used to understand the association between weight measurement, unexpected weight loss, and serious disease including cancer. Our findings will directly inform international guidelines for the management of unexpected weight loss in primary care populations.

Introduction: Changes in urinary albumin-to-creatinine ratio (UACR) may affect the risk of advanced chronic kidney disease (CKD). How much the association changes after taking account for natural variation in UACR and the length of time taken to observe changes in UACR is unknown. Methods: English Clinical Practice Research Datalink records (2000−2015) with linkage to secondary care and death certification were used to identify prospective cohorts with at least 2 measures of UACR within 1, 2, and 3 years. Adjusted Cox regression assessed the separate relevance of the baseline UACR and the UACR change to the risk of developing stages 4 to 5 CKD and end-stage renal disease (ESRD). Associations were compared before and after accounting for the effects of the natural variation in UACR (i.e., regression to the mean). Results: A total of 212,810 individuals had baseline UACR measurements; 22% had a UACR ≥3.4 mg/mmol, and 3% had UACR ≥33.9 mg/mmol. During a median 4-year follow-up, 5976 developed stage 4 to 5 CKD, and 1076 developed ESRD. There were strong associations between baseline UACR and stage 4 to 5 CKD or ESRD risk, which doubled in strength after accounting for regression to the mean. Over 3 years, the hazard ratios (95% confidence intervals) for stage 4 to 5 CKD, relative to stable UACR, were 0.62 (0.50−0.77) for at least a halving of UACR and 2.68 (2.29−3.14) for at least a doubling of UACR. Associations were weaker for shorter exposure windows (and for cardiovascular disease or death), but strengthened after allowing for regression to the mean. Conclusion: Baseline values and subsequent medium-term increases in albuminuria are both associated with substantially increased risk of developing advanced CKD. Standard analyses, not allowing for natural variation in UACR, may underestimate these associations. Keywords: albuminuria, biomarkers, chronic, kidney failure, renal insufficiency

© 2018, The Author(s) 2018. The relative toxicity of anxiolytic and hypnotic drugs commonly used for self-poisoning was assessed using data on suicides, prescriptions and non-fatal self-poisonings in England, 2005–2012. Data on suicide by self-poisoning were obtained from the Office for National Statistics, information on intentional non-fatal self-poisoning was derived from the Multicentre Study of Self-harm in England and data on prescriptions in general practice from the Clinical Practice Research Datalink. We used two indices of relative toxicity: fatal toxicity (the number of fatal self-poisonings relative to the number of individuals prescribed each drug) and case fatality (the number of fatal relative to non-fatal self-poisonings). Diazepam was the reference drug in all analyses. Temazepam was 10 times (95% confidence interval 5.48–18.99) and zopiclone/zolpidem nine times (95% confidence interval 5.01–16.65) more toxic in overdose than diazepam (fatal-toxicity index). Temazepam and zopiclone/zolpidem were 13 (95% confidence interval 6.97–24.41) and 12 (95% confidence interval 6.62–22.17) times more toxic than diazepam, respectively (case-fatality index). Differences in alcohol involvement between the drugs were unlikely to account for the findings. Overdoses of temazepam and zopiclone/zolpidem are considerably more likely to result in death than overdoses of diazepam. Practitioners need to exercise caution when prescribing these drugs, especially for individuals who may be at risk of self-harm, and also consider non-pharmacological options.

Background Bipolar and other psychiatric disorders are associated with considerably increased risk of suicidal behaviour, which may include self-poisoning with medication used to treat the disorder. Therefore, choice of medication for treatment should include consideration of toxicity, especially for patients at risk. The aim of this study was to estimate the relative toxicity of specific drugs within two drug categories, antipsychotics and mood stabilizers, using large-scale databases to provide evidence that could assist clinicians in making decisions about prescribing, especially for patients at risk of suicidal behaviour. Method Two indices were used to assess relative toxicity of mood stabilisers and antipsychotics: case fatality (the ratio between rates of fatal and non-fatal self-poisoning) and fatal toxicity (the ratio between rates of fatal self-poisoning and prescription). Mood stabilisers assessed included lithium [reference], sodium valproate, carbamazepine, and lamotrigine, while antipsychotics included chlorpromazine [reference], clozapine, olanzapine, quetiapine and risperidone. Fatal self-poisoning (suicide) data were provided by the Office for National Statistics (ONS), non-fatal self-poisoning data by the Multicentre Study of Self-harm in England, and information on prescriptions by the Clinical Practice Research Datalink. The primary analysis focussed on deaths due to a single drug. Cases where the drug of interest was listed as the likely primary toxic agent in multiple drug overdoses were also analysed. The study period was 2005–2012. Results There appeared to be little difference in toxicity between the mood stabilisers, except that based on case fatality where multiple drug poisonings were considered, carbamazepine was over twice as likely to result in death relative to lithium (OR 2.37 95% CI 1.16–4.85). Of the antipsychotics, clozapine was approximately18 times more likely to result in death when taken in overdose than chlorpromazine (single drug case fatality: OR 18.53 95% CI 8.69–39.52). Otherwise, only risperidone differed from chlorpromazine, being less toxic (OR 0.06 95% CI 0.01–0.47). Conclusions There was little difference in toxicity of the individual mood stabilisers. Clozapine was far more toxic than the other antipsychotics. The findings are relevant to prescribing policy, especially for patients at particular risk of suicidal behaviour.

BackgroundSafety netting is a diagnostic strategy used in UK primary care to ensure patients are monitored until their symptoms or signs are explained. Despite being recommended in cancer diagnosis guidelines, little evidence exists about which components are effective and feasible in modern-day primary care.AimTo understand the reality of safety netting for cancer in contemporary primary care.Design and settingA qualitative study of GPs in Oxfordshire primary care.MethodIn-depth interviews with a purposive sample of 25 qualified GPs were undertaken. Interviews were recorded and transcribed verbatim, and analysed thematically using constant comparison.ResultsGPs revealed uncertainty about which aspects of clinical practice are considered safety netting. They use bespoke personal strategies, often developed from past mistakes, without knowledge of their colleagues’ practice. Safety netting varied according to the perceived risk of cancer, the perceived reliability of each patient to follow advice, GP working patterns, and time pressures. Increasing workload, short appointments, and a reluctance to overburden hospital systems or create unnecessary patient anxiety have together led to a strategy of selective active follow-up of patients perceived to be at higher risk of cancer or less able to act autonomously. This left patients with low-risk-but-not-no-risk symptoms of cancer with less robust or absent safety netting.ConclusionGPs would benefit from clearer guidance on which aspects of clinical practice contribute to effective safety netting for cancer. Practice systems that enable active follow-up of patients with low-risk-but-not-no-risk symptoms, which could represent malignancy, could reduce delays in cancer diagnosis without increasing GP workload.

ObjectivesConsultation duration has previously been shown to be associated with patient, practitioner and practice characteristics. However, previous studies were conducted outside the UK, considered only small numbers of general practitioner (GP) consultations or focused primarily on practitioner-level characteristics. We aimed to determine the patient-level and practice-level factors associated with duration of GP and nurse consultations in UK primary care.Design and settingCross-sectional data were obtained from English general practices contributing to the Clinical Practice Research Datalink (CPRD) linked to data on patient deprivation and practice staffing, rurality and Quality and Outcomes Framework (QOF) achievement.Participants218 304 patients, from 316 English general practices, consulting from 1 April 2013 to 31 March 2014.AnalysisMultilevel mixed-effects models described the association between consultation duration and patient-level and practice-level factors (patient age, gender, smoking status, ethnic group, deprivation and practice rurality, number of full-time equivalent GPs/nurses, list size, consultation rate, quintile of overall QOF achievement and training status).ResultsMean duration of face-to-face GP consultations was 9.24 min and 5.32 min for telephone consultations. Nurse face-to-face and telephone consultations lasted 9.70 and 5.73 min on average, respectively. Longer GP consultation duration was associated with female patient gender, practice training status and older patient age. Shorter duration was associated with higher deprivation and consultation rate. Longer nurse consultation duration was associated with male patient gender, older patient age and ever smoking; and shorter duration with higher consultation rate. Observed differences in duration were small (eg, GP consultations with female patients compared with male patients were 8 s longer on average).ConclusionsSmall observed differences in consultation duration indicate that patients are treated similarly regardless of background. Increased consultation duration may be beneficial for older or comorbid patients, but the benefits and costs of increased consultation duration require further study.

ObjectiveTo estimate the proportion of systematic reviews that meet the optimal information size (OIS) and assess the impact heterogeneity and effect size have on the OIS estimate by type of outcome (eg, mortality, semiobjective or subjective).MethodsWe carried out searches of Medline and Cochrane to retrieve meta-analyses published in systematic reviews from 2010 to 2012. We estimated the OIS usingTrial Sequential Analysissoftware (TSA V.0.9) and based on several heterogeneity and effect size scenarios, stratifying by type of outcome (mortality/semiobjective/subjective) and by Cochrane/non-Cochrane reviews.ResultsWe included 137 meta-analyses out of 218 (63%) potential systematic reviews (one meta-analysis from each systematic review). Of these reviews, 83 (61%) were Cochrane and 54 (39%) non-Cochrane. The Cochrane reviews included a mean of 6.5 (SD 6.1) studies and the non-Cochrane included a mean of 13.2 (SD 10.2) studies. The mean number of patients was 2619.1 (SD 6245.8 or median 586.0) for the Cochrane and 19 888.5 (SD 32 925.7 or median 6566.5) patients for the non-Cochrane reviews. The percentage of systematic reviews that achieved the OIS for all-cause mortality outcome were 0% Cochrane and 25% for non-Cochrane reviews; for semiobjective outcome 17% for Cochrane and 46% for non-Cochrane reviews and for subjective outcome 45% for Cochrane and 72% for non-Cochrane reviews.ConclusionsThe number of systematic reviews that meet an optimal information size is low and varies depending on the type of outcome and the type of publication. Less than half of primary outcomes synthesised in systematic reviews achieve the OIS, and therefore the conclusions are subject to substantial uncertainty.

Background We describe the prevalence of births after subfertility and fertility treatment seen in primary care in England between 1991 and 2013 and and examine the impact of changing maternal characteristics over time. Methods Data from the Clinical Practice Research Datalink (CPRD) Mother-Baby dataset were used, comprising records from >600 general practices across England, linked to index of multiple deprivation (IMD). 4 40 623 mothers registered for >18 months prior to the birth of their child were included; 2 39 781 first-time mothers were analysed separately to assess changes in primary infertility. Fertility history was identified using details of diagnoses, referrals and prescriptions in GP records, and grouped as: ‘no evidence of fertility problems’ and ‘any subfertility’ (comprising ‘untreated’, ‘ovulation induction’ (OI), and ‘Assisted Reproductive Technologies’ (ART), such as IVF). Change in the prevalence of births by fertility group and population characteristics was assessed using chi-squared trend tests. Direct age-standardisation (to 1991 study population) accounted for changing population structure. Results Overall, 4.7% of mothers experienced subfertility (1991: 1.7%–2013: 6.3%), comprising: untreated 2.6% (1991: 0.6%–2013: 3.5%), OI 0.8% (1991: 0.6%; peaking in 1995: 1.3%; 2013: 0.5%), and ART 1.3% (1991: 0.5%–2013: 2.4%) (all p 35 years in 1991, rising to 27% by 2013. Age-adjusted 2013 figures were 3.1%, 1.8%, 0.2% and 1.1%, for all, untreated, OI and ART respectively. 6.6% of first-time mothers experienced subfertility (1991: 2.1%–2013: 9.7%): comprising untreated 3.6% (1991: 0.8%–2013: 5.2%), OI 1.0% (1991: 0.7%–2013: 0.6%), and ART 2.0% (1991: 0.7%–2013: 3.9%) (all p Discussion Births to women with records of fertility problems have significantly increased between 1991 and 2013. Changes in maternal age explain much of the population-level trends, but less of the observed increase among first-time mothers. Declining births after OI prescribed in primary care may reflect changing management of patients. Medical advice must continue to highlight the effect of age on fertility, and the implications for secondary infertility. GPs and service commissioners should be aware that time trends indicate continuing growth in demand for fertility treatment in England.

BackgroundWorkload in general practice has risen during the last decade, but the factors associated with this increase are unclear.AimTo examine factors associated with consultation rates in general practice.Design and settingA cross-sectional study examining a sample of 304 937 patients registered at 316 English practices between 2013 and 2014, drawn from the Clinical Practice Research Datalink.MethodAge, sex, ethnicity, smoking status, and deprivation measures were linked with practice-level data on staffing, rurality, training practice status, and Quality and Outcomes Framework performance. Multilevel analyses of patient consultation rates were conducted.ResultsConsultations were grouped into three types: all (GP or nurse), GP, and nurse. Non-smokers consulted less than current smokers (all: rate ratio [RR] = 0.88, 95% CI = 0.87 to 0.89; GP: RR = 0.88, 95% CI = 0.87 to 0.89; nurse: RR = 0.91, 95% CI = 0.90 to 0.92). Consultation rates were higher for those in the most deprived quintile compared with the least deprived quintile (all: RR = 1.18, 95% CI = 1.16 to 1.19; GP: RR = 1.17, 95% CI = 1.15 to 1.19; nurse: RR = 1.13, 95% CI = 1.11 to 1.15). For all three consultation types, consultation rates increased with age and female sex, and varied by ethnicity. Rates in practices with >8 and ≤19 full-time equivalent (FTE) GPs were higher compared with those with ≤2 FTE GPs (all: RR = 1.26, 95% CI = 1.06 to 1.49; GP: RR = 1.36, 95% CI = 1.19 to 1.56).ConclusionThe analyses show consistent trends in factors related to consultation rates in general practice across three types of consultation. These data can be used to inform the development of more sophisticated staffing models, and resource allocation formulae.

Purpose Preexisting diabetes is associated with increased morbidity and mortality in cancer. We examined the impact of incident cancer on the long-term outcomes of diabetes. Methods Using the United Kingdom Clinical Practice Research Datalink, we identified three cohorts of diabetes patients subsequently diagnosed with breast, colorectal, or prostate cancer, each matched to diabetic noncancer controls. Patients were required to have survived at least 1 year after cancer diagnosis (cases) or a matched index date (controls), and were followed up to 10 years for incident microvascular and macrovascular complications and mortality. Multivariate competing risks regression analyses were used to compare outcomes between cancer patients and controls. Results Overall, there were 3382 cancer patients and 11,135 controls with 59,431 person-years of follow-up. In adjusted analyses, there were no statistically significant (p ≤ 0.05) differences in diabetes complication rates between cancer patients and their controls in any of the three cancer cohorts. Combined, cancer patients were less likely (adjusted hazard ratio [HR] 0.88; 95% CI = 0.79–0.98) to develop retinopathy. Cancer patients were more likely to die of any cause (including cancer), but prostate cancer patients were less likely to die of causes associated with diabetes (HR 0.61; 95% CI = 0.43–0.88). Conclusions and implications There is no evidence that incident cancer had an adverse impact on the long-term outcomes of preexisting diabetes. Implications for Cancer Survivors These findings are important for cancer survivors with preexisting diabetes because they suggest that substantial improvements in the relative survival of several of the most common types of cancer are not undermined by excess diabetes morbidity and mortality.

© 2017 Herrington et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background It is uncertain whether being overweight, but not obese, is associated with advanced chronic kidney disease (CKD) and how the size and shape of associations between body-mass index (BMI) and advanced CKD differs among different types of people. Methods We used Clinical Practice Research Datalink records (2000-2014) with linkage to English secondary care and mortality data to identify a prospective cohort with at least one BMI measure. Cox models adjusted for age, sex, smoking and social deprivation and subgroup analyses by diabetes, hypertension and prior cardiovascular disease assessed relationships between BMI and CKD stages 4-5 and end-stage renal disease (ESRD). Findings 1,405,016 adults aged 20-79 with mean BMI 27.4kg/m2 (SD 5.6) were followed for 7.5 years. Compared to a BMI of 20 to

Background Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B-type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. Objectives To assess whether treatment guided by serial BNP or NT-proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. Search methods Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. Selection criteria We included randomised controlled trials of NP-guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow-up. Adults treated for heart failure, in both in-hospital and out-of-hospital settings, and trials reporting a clinical outcome were included. Data collection and analysis Two review authors independently selected studies for inclusion, extracted data and evaluated risk of bias. Risk ratios (RR) were calculated for dichotomous data, and pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated for continuous data. We contacted trial authors to obtain missing data. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, we assessed the quality of the evidence and GRADE profiler (GRADEPRO) was used to import data from Review Manager to create a 'Summary of findings' table. Main results We included 18 randomised controlled trials with 3660 participants (range of mean age: 57 to 80 years) comparing NP-guided treatment with clinical assessment alone. The evidence for all-cause mortality using NP-guided treatment showed uncertainty (RR 0.87, 95% CI 0.76 to 1.01; patients = 3169; studies = 15; low quality of the evidence), and for heart failure mortality (RR 0.84, 95% CI 0.54 to 1.30; patients = 853; studies = 6; low quality of evidence). The evidence suggested heart failure admission was reduced by NP-guided treatment (38% versus 26%, RR 0.70, 95% CI 0.61 to 0.80; patients = 1928; studies = 10; low quality of evidence), but the evidence showed uncertainty for all-cause admission (57% versus 53%, RR 0.93, 95% CI 0.84 to 1.03; patients = 1142; studies = 6; low quality of evidence). Six studies reported on adverse events, however the results could not be pooled (patients = 1144; low quality of evidence). Only four studies provided cost of treatment results, three of these studies reported a lower cost for NP-guided treatment, whilst one reported a higher cost (results were not pooled; patients = 931, low quality of evidence). The evidence showed uncertainty for quality of life data (MD -0.03, 95% CI -1.18 to 1.13; patients = 1812; studies = 8; very low quality of evidence). We completed a 'Risk of bias' assessment for all studies. The impact of risk of bias from lack of blinding of outcome assessment and high attrition levels was examined by restricting analyses to only low 'Risk of bias' studies. Authors' conclusions In patients with heart failure low-quality evidence showed a reduction in heart failure admission with NP-guided treatment while low-quality evidence showed uncertainty in the effect of NP-guided treatment for all-cause mortality, heart failure mortality, and all-cause admission. Uncertainty in the effect was further shown by very low-quality evidence for patient's quality of life. The evidence for adverse events and cost of treatment was low quality and we were unable to pool results. B-type natriuretic peptide-guided treatment for heart failure patients Review question We aimed to discover whether using B-type natriuretic-guided treatment or a health plan alone is more effective for managing patients with heart failure. Background Heart failure is a complex condition that occurs when the heart does not pump blood effectively enough to meet the needs of the body. It is caused by a range of diseases that impair the structure and function of the heart and may result in breathlessness, fatigue and fluid retention. People with heart failure are frequently users of general practice and hospitals, particularly as inpatients. Furthermore, they have reduced life expectancy, although medicines and other treatments can improve the chance of survival. B-type natriuretic peptide (NP) is a substance produced in the heart. The measurement of NP can be used to indicate the condition of the heart. For some time, NP has been used for diagnosing heart failure and predicting what is likely to happen. We wanted to discover if NP may also offer a way to manage and make the best use of medicines. Study selection and characteristics We carried out a review of all studies and the evidence is current to 15 March 2016. We found 18 studies of NP-guided treatment in which 3660 patients with heart failure took part. Patients were between 62 to 80 years old at the start of the studies. The duration of each study ranged from one to 54 months. Eight out of the 18 studies were part or fully funded by pharmaceutical companies, one was funded by a national research body, five were partially funded either by national research grants, lotteries, hospital funds and/or pharmaceutical companies and four studies did not report the funding source. Key results The evidence was unclear as to whether number of deaths from any cause varied between patients with heart failure using NP-guided treatment compared with those using a health plan alone. Nor was it clear as to whether there were less deaths when the results were separated into patients older or younger than 75 years old (age results only included three studies). Furthermore, we found that the evidence was unclear whether the number of deaths from heart failure alone varied between the NP-guided treatment or health plan alone groups. We found that hospital admission due to heart failure may be reduced in the patients using NP-guided treatment compared with a health plan alone. Based on these results we would expect that out of 1000 patients with heart failure who are guided by a health plan alone, 377 would experience an admission to hospital due to heart failure. Whereas, between 230 and 301 patients would experience an admission to hospital due to heart failure if they received NP-guided treatment. However, the evidence was unclear as to whether the numbers of hospital admission from any cause were affected. There was limited information about either harms to patients, or the cost of the treatment. It was not possible to combine the results from these studies for these outcomes. However, four of the six studies commented that they found no difference in harms or less difference in harms between the patients using NP-guided treatment compared with a health plan alone, the other two studies did not comment. Four studies reported results on costs, three of these reported there may be lower costs in the NP-guided treatment groups compared with health plan groups. Lower costs appeared to be due to less cost for hospital stays. However, one study reported that NP-guided treatment was unlikely to be cost-effective. The evidence was unclear as to if a benefit was shown in the replies to quality-of-life surveys when comparing between NP-guided treatment and health plan only groups. Quality of evidence Overall evidence for death from all causes, from heart failure alone and for hospital admission was of low quality. For harm to patients and cost outcomes the quality of evidence was low, whilst evidence for patients' quality of life surveys was very low. For all outcomes there was little evidence due to the way the studies were conducted. In addition, for harm to patients and cost of treatment there were differences in the type of information available.