The Association between Blood Test Trends and Undiagnosed Cancer: A Systematic Review and Critical Appraisal.

Clinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient's individual baseline and important changes within the normal range. We aimed to review the published literature to understand the association between blood test trends and undiagnosed cancer. MEDLINE and EMBASE were searched until 15 May 2023 for studies assessing the association between blood test trends and undiagnosed cancer. We used descriptive summaries and narratively synthesised studies. We included 29 articles. Common blood tests were haemoglobin (24%, n = 7), C-reactive protein (17%, n = 5), and fasting blood glucose (17%, n = 5), and common cancers were pancreatic (29%, n = 8) and colorectal (17%, n = 5). Of the 30 blood tests studied, an increasing trend in eight (27%) was associated with eight cancer types, and a decreasing trend in 17 (57%) with 10 cancer types. No association was reported between trends in 11 (37%) tests and breast, bile duct, glioma, haematological combined, liver, prostate, or thyroid cancers. Our review highlights trends in blood tests that could facilitate the identification of individuals at increased risk of undiagnosed cancer. For most possible combinations of tests and cancers, there was limited or no evidence.

Ethnic inequities in 6-8 week baby check coverage in England 2006-2021: a cohort study using the Clinical Practice Research Datalink.

BACKGROUND: Inequities in the coverage of 6-8 week maternal checks, health visitor reviews and infant vaccinations have been reported in England. Ethnic inequities in 6-8 week baby checks have not been studied nationally. AIM: To examine the effect of maternal ethnicity on 6-8 week baby check coverage in England 2006-2021. DESIGN AND SETTING: Cohort study using electronic health records. METHODS: We calculated baby check coverage in 16 ethnic groups, by year and region, and risk ratios using modified Poisson regression. We calculated coverage and timing of baby checks in relation to maternal checks and infant vaccinations by ethnic group. RESULTS: Ethnic inequities in 6-8 week baby check coverage in England varied by year and region. Coverage increased 2006-07 to 2015-16, then stabilised to 80-90% for most groups. Coverage was lowest for Bangladeshi and Pakistani groups 2006-07 to 2011-12. In the West Midlands, coverage was lowest at 59% for four groups: Bangladeshi, Caribbean, African, and Any other Black, African or Caribbean background. In the North West, coverage was lowest for Bangladeshi (65%) and Pakistani (69%) groups. These patterns remained after adjusting for other factors, and persisted over time. Coverage was highest in those whose mothers received a maternal check and those who received at least one dose of 8 week infant vaccinations. CONCLUSIONS: Coordinated action at the level of integrated commissioning boards, primary care networks and GP practices is required to better understand the reasons behind these inequities and redress the persistent disparities in 6-8 week baby check coverage.

Ethnic inequities in routine childhood vaccinations in England 2006-2021: an observational cohort study using electronic health records.

Background: Population groups that are underserved by England's childhood vaccination programme must be identified to address the country's declining vaccination coverage. We examined routine childhood vaccination coverage in England by maternal ethnicity between 2006 and 2021. Methods: We created first, second and fifth birthday cohorts using mother-child linked electronic health records from the Clinical Practice Research Datalink (CPRD) Aurum. After validation against the UK Health Security Agency (UKHSA) and National Health Service England (NHSE) annual statistical reports, we described vaccination coverage for each vaccine by ethnicity and year. We used modified Poisson regression to analyse the effect of ethnicity on receiving the primary and full course of each vaccine. Findings: Up to 1,170,804 children born after 1 April 2006 were included in the first birthday cohort, reducing to 645,492 by the fifth birthday. Children were followed up until 31 March 2021 at the latest. Children born to mothers in 9 minority ethnic groups and those of unknown ethnicity had lower vaccination coverage (61.3-97.5%) than the White British group (79.9-97.8%) for all vaccines. Indian, Pakistani, Bangladeshi, Chinese, Any other Asian background, and White and Asian ethnic groups had similar vaccination coverage to the White British group (above 90% for most vaccines in most years). Inequities particularly affected the Caribbean group (e.g. 61% coverage for the 6/5/4-in-1 full course in 2020-21 by children's fifth birthday; RR 0.66, 95% CI 0.6-0.74 compared with the White British group) and Any other Black, African and Caribbean background (e.g. coverage 68% for the MMR primary course in 2020-21; RR 0.71, 95% CI 0.64-0.78). These inequities widened over the study period. For example, the absolute difference in coverage between the Caribbean and White British groups for the full course of MMR increased from 12% in 2011-12 to 22% in 2019-20. These inequities remained even after accounting for sociodemographic, maternal and birth related factors, and also widened from primary course to full course. Interpretation: Our findings suggest that urgent policy action is needed to address the ethnic inequities throughout England's routine childhood vaccination programme, which have been worsening over time. Funding: University of Oxford Clarendon Fund, St Cross College and Nuffield Department of Population Health.

Electronic safety-netting tool features considered important by UK general practice staff: an interview and Delphi consensus study.

BACKGROUND: The potential of the electronic health record to support safety netting has been recognised and a number of electronic safety-netting (E-SN) tools developed. AIM: To establish the most important features of E-SN tools. DESIGN & SETTING: User-experience interviews followed by a Delphi study in a primary care setting in the UK. METHOD: The user-experience interviews were carried out remotely with primary care staff who had trialled the EMIS E-SN toolkit for suspected cancer. An electronic modified Delphi approach was used, with primary care staff involved in safety netting in any capacity, to measure consensus on tool features. RESULTS: Thirteen user-experience interviews were carried out and features of E-SN tools seen as important formed the majority of the features included in the Delphi study. Three rounds of Delphi survey were administered. Sixteen responders (64%) completed all three rounds, and 28 out of 44 (64%) features reached consensus. Primary care staff preferred tools that were general in scope. CONCLUSION: Primary care staff indicated that tools that were not specific to cancer or any other disease, and had features that promoted their flexible, efficient, and integrated use, were important. However, when the important features were discussed with the patient and public involvement (PPI) group, they expressed disappointment that features they believed would make E-SN tools robust and provide a safety net that is difficult to fall through did not reach consensus. The successful adoption of E-SN tools will rely on an evidence base of their effectiveness. Efforts should be made to assess the impact of these tools on patient outcomes.

BLOod Test Trend for cancEr Detection (BLOTTED): protocol for an observational and prediction model development study using English primary care electronic health record data.

BACKGROUND: Simple blood tests can play an important role in identifying patients for cancer investigation. The current evidence base is limited almost entirely to tests used in isolation. However, recent evidence suggests combining multiple types of blood tests and investigating trends in blood test results over time could be more useful to select patients for further cancer investigation. Such trends could increase cancer yield and reduce unnecessary referrals. We aim to explore whether trends in blood test results are more useful than symptoms or single blood test results in selecting primary care patients for cancer investigation. We aim to develop clinical prediction models that incorporate trends in blood tests to identify the risk of cancer. METHODS: Primary care electronic health record data from the English Clinical Practice Research Datalink Aurum primary care database will be accessed and linked to cancer registrations and secondary care datasets. Using a cohort study design, we will describe patterns in blood testing (aim 1) and explore associations between covariates and trends in blood tests with cancer using mixed-effects, Cox, and dynamic models (aim 2). To build the predictive models for the risk of cancer, we will use dynamic risk modelling (such as multivariate joint modelling) and machine learning, incorporating simultaneous trends in multiple blood tests, together with other covariates (aim 3). Model performance will be assessed using various performance measures, including c-statistic and calibration plots. DISCUSSION: These models will form decision rules to help general practitioners find patients who need a referral for further investigation of cancer. This could increase cancer yield, reduce unnecessary referrals, and give more patients the opportunity for treatment and improved outcomes.

Step-Wise Management of Anemia in Patients With Chronic Kidney Disease in Primary Care: Qualitative Study.

INTRODUCTION: Anemia is common in chronic kidney disease (CKD) and is associated with increased cardiovascular risk and reduced quality of life, but is often sub-optimally managed. Most patients are managed in primary care alongside other comorbidities. Interventions to improve the management of anemia in CKD in this setting are needed. METHODS: We conducted a qualitative study to evaluate how an audit-based education (ABE) intervention might improve the management of anemia in CKD. We explored outcomes that would be relevant to practitioners and patients, that exposed variation of practice from National Institute for Health and Care Excellence (NICE) guidelines, and whether the intervention was feasible and acceptable. RESULTS: Practitioners (n = 5 groups) and patients (n = 7) from 4 London general practices participated in discussions. Practitioners welcomed the evidence-based step-wise intervention. However, prescribing erythropoiesis-stimulating agents (ESAs) was felt to be outside of their scope of practice. There was a gap between NICE guidance and clinical practice in primary care. Iron studies were not well understood and anemia management was often conservative or delayed. Patients were often unaware of having CKD, and were more concerned about their other comorbidities, but largely trusted their GPs to manage them appropriately. CONCLUSIONS: The first steps of the intervention were welcomed by practitioners, but they expressed concerns about independently prescribing ESAs. Renal physicians and GPs could develop shared care protocols for ESA use in primary care. There is scope to improve awareness of renal anemia, and enhance knowledge of guideline recommendations; and our intervention should be modified accordingly.

Ethnic differences and inequities in paediatric healthcare utilisation in the UK: a scoping review.

BACKGROUND: Despite the increased policy attention on ethnic health inequities since the COVID-19 pandemic, research on ethnicity and healthcare utilisation in children has largely been overlooked. OBJECTIVES: This scoping review aimed to describe and appraise the quantitative evidence on ethnic differences (unequal) and inequities (unequal, unfair and disproportionate to healthcare needs) in paediatric healthcare utilisation in the UK 2001-2021. METHODS: We searched Embase, Medline and grey literature sources and mapped the number of studies that found differences and inequities by ethnic group and healthcare utilisation outcome. We summarised the distribution of studies across various methodological parameters. RESULTS: The majority of the 61 included studies (n=54, 89%) identified ethnic differences or inequities in paediatric healthcare utilisation, though inequities were examined in fewer than half of studies (n=27, 44%). These studies mostly focused on primary and preventive care, and depending on whether ethnicity data were aggregated or disaggregated, findings were sometimes conflicting. Emergency and outpatient care were understudied, as were health conditions besides mental health and infectious disease. Studies used a range of ethnicity classification systems and lacked the use of theoretical frameworks. Children's ethnicity was often the explanatory factor of interest while parent/caregiver ethnicity was largely overlooked. DISCUSSION: While the current evidence base can assist policy makers to identify inequities in paediatric healthcare utilisation among certain ethnic groups, we outline recommendations to improve the validity, generalisability and comparability of research to better understand and thereby act on ethnic inequities in paediatric healthcare.

Representativeness, Vaccination Uptake, and COVID-19 Clinical Outcomes 2020-2021 in the UK Oxford-Royal College of General Practitioners Research and Surveillance Network: Cohort Profile Summary.

BACKGROUND: The Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) is one of Europe's oldest sentinel systems, working with the UK Health Security Agency (UKHSA) and its predecessor bodies for 55 years. Its surveillance report now runs twice weekly, supplemented by online observatories. In addition to conducting sentinel surveillance from a nationally representative group of practices, the RSC is now also providing data for syndromic surveillance. OBJECTIVE: The aim of this study was to describe the cohort profile at the start of the 2021-2022 surveillance season and recent changes to our surveillance practice. METHODS: The RSC's pseudonymized primary care data, linked to hospital and other data, are held in the Oxford-RCGP Clinical Informatics Digital Hub, a Trusted Research Environment. We describe the RSC's cohort profile as of September 2021, divided into a Primary Care Sentinel Cohort (PCSC)-collecting virological and serological specimens-and a larger group of syndromic surveillance general practices (SSGPs). We report changes to our sampling strategy that brings the RSC into alignment with European Centre for Disease Control guidance and then compare our cohort's sociodemographic characteristics with Office for National Statistics data. We further describe influenza and COVID-19 vaccine coverage for the 2020-2021 season (week 40 of 2020 to week 39 of 2021), with the latter differentiated by vaccine brand. Finally, we report COVID-19-related outcomes in terms of hospitalization, intensive care unit (ICU) admission, and death. RESULTS: As a response to COVID-19, the RSC grew from just over 500 PCSC practices in 2019 to 1879 practices in 2021 (PCSC, n=938; SSGP, n=1203). This represents 28.6% of English general practices and 30.59% (17,299,780/56,550,136) of the population. In the reporting period, the PCSC collected >8000 virology and >23,000 serology samples. The RSC population was broadly representative of the national population in terms of age, gender, ethnicity, National Health Service Region, socioeconomic status, obesity, and smoking habit. The RSC captured vaccine coverage data for influenza (n=5.4 million) and COVID-19, reporting dose one (n=11.9 million), two (n=11 million), and three (n=0.4 million) for the latter as well as brand-specific uptake data (AstraZeneca vaccine, n=11.6 million; Pfizer, n=10.8 million; and Moderna, n=0.7 million). The median (IQR) number of COVID-19 hospitalizations and ICU admissions was 1181 (559-1559) and 115 (50-174) per week, respectively. CONCLUSIONS: The RSC is broadly representative of the national population; its PCSC is geographically representative and its SSGPs are newly supporting UKHSA syndromic surveillance efforts. The network captures vaccine coverage and has expanded from reporting primary care attendances to providing data on onward hospital outcomes and deaths. The challenge remains to increase virological and serological sampling to monitor the effectiveness and waning of all vaccines available in a timely manner.

The Variations in Care and Real-world Outcomes in Individuals With Rectal Cancer: Protocol for the Ontario Rectal Cancer Cohort.

BACKGROUND: Individuals with rectal cancer require a number of pretreatment investigations, often require multidisciplinary treatment, and require ongoing follow-ups after treatment is completed. Due to the complexity of treatments, large variations in practice patterns and outcomes have been identified. At present, few comprehensive, population-level data sets are available for assessing interventions and outcomes in this group. OBJECTIVE: Our study aims to create a comprehensive database of individuals with rectal cancer who have been treated in a single-payer, universal health care system. This database will provide an excellent resource that investigators can use to study variations in the delivery of care to and real-world outcomes of this population. METHODS: The Ontario Rectal Cancer Cohort database will include comprehensive details about the management and outcomes of individuals with rectal cancer who have been diagnosed in Ontario, Canada (population: 14.6 million), between 2010 and 2019. Linked administrative data sets will be used to construct this comprehensive database. Individual and care provider characteristics, investigations, treatments, follow-ups, and outcomes will be derived and linked. Surgical pathology details, including the stage of disease, histopathology characteristics, and the quality of surgical excision, will be included. Ethics approval for this study was obtained through the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board. RESULTS: Approximately 20,000 individuals who meet the inclusion criteria for this study have been identified. Data analysis is ongoing, with an expected completion date of March 2023. This study was funded through the Canadian Institute of Health Research Operating Grant. CONCLUSIONS: The Ontario Rectal Cancer Cohort will include a comprehensive data set of individuals with rectal cancer who received care within a single-payer, universal health care system. This cohort will be used to determine factors associated with regional variability and adherence to recommended care, and it will allow for an assessment of a number of understudied areas within the delivery of rectal cancer treatment. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/38874.

Primary care practice and cancer suspicion during the first three COVID-19 lockdowns in the UK: a qualitative study.

BACKGROUND: The COVID-19 pandemic has profoundly affected UK primary care, and as a result the route to cancer diagnosis for many patients. AIM: To explore how the pandemic affected primary care practice, in particular cancer suspicion, referral, and diagnosis, and how this experience evolved as the pandemic progressed. DESIGN AND SETTING: Seventeen qualitative interviews were carried out remotely with primary care staff. METHOD: Staff from practices in England that expressed an interest in trialling an electronic safety-netting tool were invited to participate. Remote, semi-structured interviews were conducted from September 2020 to March 2021. Data analysis followed a thematic analysis and mind-mapping approach. RESULTS: The first lockdown was described as providing time to make adjustments to allow remote and minimal-contact consultations but caused concerns over undetected cancers. These concerns were realised in summer and autumn 2020 as the participants began to see higher rates of late-stage cancer presentation. During the second and third lockdowns patients seemed more willing to consult. This combined with usual winter pressures, demands of the vaccine programme, and surging levels of COVID-19 meant that the third lockdown was the most difficult. New ways of working were seen as positive when they streamlined services but also unsafe if they prevented GPs from accessing all relevant information and resulted in delayed cancer diagnoses. CONCLUSION: The post-pandemic recovery of cancer care is dependent on the recovery of primary care. The COVID-19 pandemic has highlighted and exacerbated vulnerabilities in primary care but has also provided new ways of working that may help the recovery.

The association between conception history and subsequent postpartum depression and/or anxiety: Evidence from the Clinical Practice Research Datalink 1991-2013.

BACKGROUND: Infertility, and fertility treatment, are associated with psychological distress that may influence subsequent mental health including postpartum depression and anxiety. METHODS: Data for women who had a livebirth between 1991 and 2013 were drawn from the Clinical Practice Research Datalink. Conception history prior to their first recorded birth was categorised as 'no fertility problems', 'untreated subfertility', ovulation induction (OI), and assisted reproductive technologies (ART). Depression and/or anxiety in the 12 months postpartum were identified using records of diagnoses, symptoms, and prescriptions. Prevalence was compared, and odds ratios estimated using multivariable logistic regression. RESULTS: Of 235,127 mothers, 31,947 (13.6%) had evidence of postpartum depression and/or anxiety. Mothers in the ART group had 22% lower odds of postnatal depression and/or anxiety compared to mothers in the fertile group (OR 0.78; 95% CI [0.70-0.86]; p < 0.0001). Accounting for prior mental health, lifestyle, sociodemographic and pregnancy-related factors reduced the strength of the association (aOR 0.87; 95% CI [0.78-0.97]; p = 0.01). There were no significant associations observed in the untreated subfertility or OI groups. LIMITATIONS: As in any analysis of routine data, the quality of recording is important and some information was unavailable (e.g. education, social support). CONCLUSIONS: Women with a history of subfertility, OI or ART treatment were not at increased risk of postpartum depression and/or anxiety compared to those with no fertility problems. It is important to explore whether women who underwent ART are less likely to experience depression/anxiety or do not seek help when needed, with implications for their health and care.

National rates and disparities in childhood vaccination and vaccine-preventable disease during the COVID-19 pandemic: English sentinel network retrospective database study.

OBJECTIVES: To describe rates and variation in uptake of pneumococcal and measles, mumps and rubella (MMR) vaccines in children and associated change in vaccine-preventable diseases (VPDs) across the first and second waves of the COVID-19 pandemic. METHODS: Retrospective database study of all children aged <19 registered with a general practice in the Oxford Royal College of General Practitioners Research and Surveillance Centre English national sentinel surveillance network between 2 November 2015 and 18 July 2021. RESULTS: Coverage of booster dose of pneumococcal vaccine decreased from 94.5% (95% CI 94.3% to 94.7%) at its height on International Organization for Standardization (ISO) week 47 (2020) to 93.6% (95% CI 93.4% to 93.8%) by the end of the study. Coverage of second dose of MMR decreased from 85.0% (95% CI 84.7% to 85.3%) at its height on ISO week 37 (2020) to 84.1% (95% CI 83.8% to 84.4%) by the end of the study. The break point in trends for MMR was at ISO week 34 (2020) (95% CI weeks 32-37 (2020)), while for pneumococcal vaccine the break point was later at ISO week 3 (2021) (95% CI week 53 (2020) to week 8 (2021)). Vaccination coverage for children of white ethnicity was less likely to decrease than other ethnicities. Rates of consultation for VPDs fell and remained low since August 2020. CONCLUSION: Childhood vaccination rates started to fall ahead of the onset of the second wave; this fall is accentuating ethnic, socioeconomic and geographical disparities in vaccine uptake and risks widening health disparities. Social distancing and school closures may have contributed to lower rates of associated VPDs, but there may be increased risk as these measures are removed.

Point-of-care NT-proBNP monitoring for heart failure: observational feasibility study in primary care.

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

Consultations for clinical features of possible cancer and associated urgent referrals before and during the COVID-19 pandemic: an observational cohort study from English primary care.

BACKGROUND: It remains unclear to what extent reductions in urgent referrals for suspected cancer during the COVID-19 pandemic were the result of fewer patients attending primary care compared to GPs referring fewer patients. METHODS: Cohort study including electronic health records data from 8,192,069 patients from 663 English practices. Weekly consultation rates, cumulative consultations and referrals were calculated for 28 clinical features from the NICE suspected cancer guidelines. Clinical feature consultation rate ratios (CRR) and urgent referral rate ratios (RRR) compared time periods in 2020 with 2019. FINDINGS: Consultations for cancer clinical features decreased by 24.19% (95% CI: 24.04-24.34%) between 2019 and 2020, particularly in the 6-12 weeks following the first national lockdown. Urgent referrals for clinical features decreased by 10.47% (95% CI: 9.82-11.12%) between 2019 and 2020. Overall, once patients consulted with primary care, GPs urgently referred a similar or greater proportion of patients compared to previous years. CONCLUSION: Due to the significant fall in patients consulting with clinical features of cancer there was a lower than expected number of urgent referrals in 2020. Sustained efforts should be made throughout the pandemic to encourage the public to consult their GP with cancer clinical features.

Statin prescription in patients with chronic obstructive pulmonary disease and risk of exacerbations: a retrospective cohort study in the Clinical Practice Research Datalink.

OBJECTIVE: Observational studies have suggested a beneficial effect of taking statins on frequency of chronic obstructive pulmonary disease (COPD) exacerbations. However, clinical trials of statins in people with COPD did not confirm those results. This study aimed to investigate this association using a methodological approach, which reduces the biases associated with some previous observational study designs. DESIGN: Retrospective cohort study comparing new-users of statins with non-users. SETTING: General practices in England contributing to the Clinical Practice Research Datalink in 2007-2017, with linkage to data on Hospital Episode Statistics inpatient episodes. PARTICIPANTS: 48 124 people with COPD, aged over 40 years, who had not been prescribed statin in the previous year. EXPOSURE: Participants became new-users of statins at their first prescription for a statin during follow-up. They were then assumed to remain statin users. Statin users were compared with non-users. OUTCOMES: Primary outcomes were COPD exacerbation, or severe exacerbation requiring hospitalisation. Secondary outcomes were death from any cause (for comparison with other studies) and urinary tract infection (negative-control). Maximum follow-up was 3 years. Adjusted HR were calculated using time-dependent Cox regression. The Andersen-Gill model was used for recurrent exacerbations. Covariates included demographic variables, variables related to COPD severity, cardiovascular comorbidities as time-dependent variables, and other comorbidities at baseline. RESULTS: 7266 participants became new-users of statins over an average 2.5 years of follow-up. In total, 30 961 people developed an exacerbation, 8110 severe exacerbation, 3650 urinary tract infection and 5355 died. Adjusted HR (95% CI) in statin users compared with non-users were first exacerbation 1.01 (0.96-1.06), severe exacerbation 0.92 (0.84-0.99), number of exacerbations 1.00 (0.97-1.04), urinary tract infection 1.10 (0.98-1.23) and death 0.63 (0.57-0.70). CONCLUSIONS: In this study of health records from a Primary Care database, statin use in people with COPD was not associated with a lower risk of COPD exacerbation.

Weight change, cardio-metabolic risk factors and cardiovascular incidence in people with serious mental illness: protocol of a population-based cohort study in the UK from 1998 to 2020.

INTRODUCTION: People 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 ANALYSIS: In 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 DISSEMINATION: This 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.

The impact of primary care supported shielding on the risk of mortality in people vulnerable to COVID-19: English sentinel network matched cohort study.

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 < 0.0001). Over the remaining nine weeks, mortality risk was 54% higher in the shielded group (HR=1.54, 95%CI:1.41-1.70, p < 0.0001). Beyond the shielding period, mortality risk was over two-and-a-half times higher in the shielded group (HR=2.61, 95%CI:2.38-2.87, p < 0.0001). CONCLUSIONS: Shielding halved the risk of mortality for 21 days. Mortality risk became higher across the remainder of the shielding period, rising to two-and-a-half times greater post-shielding. Shielding may be beneficial in the next wave of COVID-19.

Study into COVID-19 Crisis Using Primary Care Mental Health Consultations and Prescriptions Data.

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.

Frequency of Renal Monitoring - Creatinine and Cystatin C (FORM-2C): an observational cohort study of patients with reduced eGFR in primary care.

BACKGROUND: Monitoring is the mainstay of chronic kidney disease management in primary care; however, there is little evidence about the best way to do this. AIM: To compare the effectiveness of estimated glomerular filtration rate (eGFR) derived from serum creatinine and serum cystatin C to predict renal function decline among those with a recent eGFR of 30-89 ml/min/1.73 m2. DESIGN AND SETTING: Observational cohort study in UK primary care. METHOD: Serum creatinine and serum cystatin C were both measured at seven study visits over 2 years in 750 patients aged ≥18 years with an eGFR of 30-89 ml/min/1.73 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. RESULTS: Average 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 <75 years, or with eGFR ≥60 ml/min/1.73 m2. In those with eGFR <60 ml/min/1.73 m2, serum cystatin C-derived eGFR was more predictive than serum creatinine-derived eGFR for future decline in kidney function. CONCLUSION: In the primary analysis neither eGFR estimated from serum creatinine nor from serum cystatin C predicted future change in kidney function, partly due to small changes during 2 years. In some secondary analyses there was a suggestion that serum cystatin C was a more useful biomarker to estimate eGFR, especially in those with a baseline eGFR <60 ml/min/1.73 m2.