Development of a modified Cambridge Multimorbidity Score for use with SNOMED CT: an observational English primary care sentinel network study.

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

Hepatitis B virus infection in general practice across England: An analysis of the Royal College of General Practitioners Research and Surveillance Centre real-world database.

OBJECTIVES: We analyzed hepatitis B surface antigen (HBsAg) screening and seropositivity within a network of 419 general practices representative of all regions of England. METHODS: Information was extracted using pseudonymized registration data. Predictors of HBsAg seropositivity were explored in models that considered age, gender, ethnicity, time at the current practice, practice location and associated deprivation index, and presence of nationally endorsed screen indicators including pregnancy, men who have sex with men (MSM), history of injecting drug use (IDU), close HBV contact or imprisonment, and diagnosis of blood-borne or sexually transmitted infections. RESULTS: Among 6,975,119 individuals, 192,639 (2.8 %) had a screening record, including 3.6-38.6 % of those with a screen indicator, and 8065 (0.12 %) had a seropositive record. The odds of seropositivity were highest in London, in the most deprived neighborhoods, among minority ethnic groups, and in people with screen indicators. Seroprevalence exceeded 1 % in people from high-prevalence countries, MSM, close HBV contacts, and people with a history of IDU or a recorded diagnosis of HIV, HCV, or syphilis. Overall, 1989/8065 (24.7 %) had a recorded referral to specialist hepatitis care. CONCLUSIONS: In England, HBV infection is associated with poverty. There are unrealized opportunities to promote access to diagnosis and care for those affected.

Long term follow up of direct oral anticoagulants and warfarin therapy on stroke, with all-cause mortality as a competing risk, in people with atrial fibrillation: Sentinel network database study.

BACKGROUND: We investigated differences in risk of stroke, with all-cause mortality as a competing risk, in people newly diagnosed with atrial fibrillation (AF) who were commenced on either direct oral anticoagulants (DOACs) or warfarin treatment. METHODS AND RESULTS: We conducted a retrospective cohort study of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database (a network of 500 English general practices). We compared long term exposure to DOAC (n = 5,168) and warfarin (n = 7,451) in new cases of AF not previously treated with oral anticoagulants. Analyses included: survival analysis, estimating cause specific hazard ratios (CSHR), Fine-Gray analysis for factors affecting cumulative incidence of events occurring over time and a cumulative risk regression with time varying effects.We found no difference in CSHR between stroke 1.08 (0.72-1.63, p = 0.69) and all-cause mortality 0.93 (0.81-1.08, p = 0.37), or between the anticoagulant groups. Fine-Gray analysis produced similar results 1.07 (0.71-1.6 p = 0.75) for stroke and 0.93 (0.8-1.07, p = 0.3) mortality. The cumulative risk of mortality with DOAC was significantly elevated in early follow-up (67 days), with cumulative risk decreasing until 1,537 days and all-cause mortality risk significantly decreased coefficient estimate:: -0.23 (-0.38-0.01, p = 0.001); which persisted over seven years of follow-up. CONCLUSIONS: In this large, contemporary, real world primary care study with longer follow-up, we found no overall difference in the hazard of stroke between warfarin and DOAC treatment for AF. However, there was a significant time-varying effect between anti-coagulant regimen on all-cause mortality, with DOACs showing better survival. This is a key methodological observation for future follow-up studies, and reassuring for patients and health care professionals for longer duration of therapy.

Safety of routine childhood vaccine coadministration versus separate vaccination.

INTRODUCTION: As new vaccines are developed more vaccine coadministrations vaccines are being offered to make delivery more practical for health systems and patients. We compared the safety of coadministered vaccines with separate vaccination for 20 coadministrations by considering nine types of adverse events following immunisation (AEFI). METHODS: Real-life immunisation and adverse event data for this observational cohort study were extracted from the Oxford-Royal College of General Practitioners Research and Surveillance Centre for children registered in the database between 2008 and 2018. We applied the self-controlled case series method to calculate relative incidence ratios (RIR) for AEFI. These RIRs compare the RI of AEFI following coadministration with the RI following separate administration of the same vaccines. RESULTS: We assessed 3 518 047 adverse events and included 5 993 290 vaccine doses given to 958 591 children. 17% of AEFI occurred less and 11% more frequently following coadministration than would have been expected based on the RIs following separate vaccinations, while there was no significant difference for 72% of AEFI. We found amplifying interaction effects for AEFI after five coadministrations comprising three vaccines: for fever (RIR 1.93 (95% CI 1.63 to 2.29)), rash (RIR 1.49 (95% CI 1.29 to 1.74)), gastrointestinal events (RIR 1.31 (95% CI 1.14 to 1.49)) and respiratory events (RIR 1.27 (1.17-1.38)) following DTaP/IPV/Hib+MenC+ PCV; gastrointestinal events (RIR 1.65 (95% CI 1.35 to 2.02)) following DTaP/IPV/Hib+MenC+ RV; fever (RIR 1.44 (95% CI 1.09 to 1.90)) and respiratory events (RIR 1.40 (95% CI 1.25 to 1.57)) following DTaP/IPV/Hib+PCV+ RV; gastrointestinal (RIR 1.48 (95% CI 1.20 to 1.82)) and respiratory events (RIR 1.43 (95% CI 1.26 to 1.63)) following MMR+Hib/MenC+PCV; gastrointestinal events (RIR 1.68 (95% CI 1.07 to 2.64)) and general symptoms (RIR 11.83 (95% CI 1.28 to 109.01)) following MMR+MenC+PCV. Coadministration of MMR+PCV led to more fever (RIR 1.91 (95% CI 1.83 to 1.99)), neurological events (RIR 2.04 (95% CI 1.67 to 2.49)) and rash (RIR 1.06 (95% CI 1.01 to 1.11)) compared with separate administration, DTaP/IPV/Hib+MMR to more musculoskeletal events (RIR 3.56 (95% CI 1.21 to 10.50)) and MMR+MenC to more fever (RIR 1.58 (95% CI 1.37 to 1.82)). There was no indication that unscheduled coadministrations are less safe than scheduled coadministrations. CONCLUSION: Real-life RIRs of AEFI justify coadministering routine childhood vaccines according to the immunisation schedule. Further research into the severity of AEFI following coadministration is required for a complete understanding of the burden of these AEFI.

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.

Sociodemographic disparities in COVID-19 seroprevalence across England in the Oxford RCGP primary care sentinel network.

OBJECTIVES: To monitor changes in seroprevalence of SARS-CoV-2 antibodies in populations over time and between different demographic groups. METHODS: A subset of practices in the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network provided serum samples, collected when volunteer patients had routine blood tests. We tested these samples for SARS-CoV-2 antibodies using Abbott (Chicago, USA), Roche (Basel, Switzerland) and/or Euroimmun (Luebeck, Germany) assays, and linked the results to the patients' primary care computerised medical records. We report seropositivity by region and age group, and additionally examined the effects of gender, ethnicity, deprivation, rurality, shielding recommendation and smoking status. RESULTS: We estimated seropositivity from patients aged 18-100 years old, which ranged from 4.1% (95% CI 3.1-5.3%) to 8.9% (95% CI 7.8-10.2%) across the different assays and time periods. We found higher Euroimmun seropositivity in younger age groups, people of Black and Asian ethnicity (compared to white), major conurbations, and non-smokers. We did not observe any significant effect by region, gender, deprivation, or shielding recommendation. CONCLUSIONS: Our results suggest that prior to the vaccination programme, most of the population remained unexposed to SARS-CoV-2.

Mental Health Presentations Across Health Care Settings During the First 9 Months of the COVID-19 Pandemic in England: Retrospective Observational Study.

BACKGROUND: The COVID-19 pandemic has resulted in an unprecedented impact on the day-to-day lives of people, with several features potentially adversely affecting mental health. There is growing evidence of the size of the impact of COVID-19 on mental health, but much of this is from ongoing population surveys using validated mental health scores. OBJECTIVE: This study investigated the impact of the pandemic and control measures on mental health conditions presenting to a spectrum of national health care services monitored using real-time syndromic surveillance in England. METHODS: We conducted a retrospective observational descriptive study of mental health presentations (those calling the national medical helpline, National Health Service [NHS] 111; consulting general practitioners [GPs] in and out-of-hours; calling ambulance services; and attending emergency departments) from January 1, 2019, to September 30, 2020. Estimates for the impact of lockdown measures were provided using an interrupted time series analysis. RESULTS: Mental health presentations showed a marked decrease during the early stages of the pandemic. Postlockdown, attendances for mental health conditions reached higher than prepandemic levels across most systems-a rise of 10% compared to that expected for NHS 111 and 21% for GP out-of-hours service-while the number of consultations to GP in-hours service was 13% lower compared to the same time previous year. Increases were observed in calls to NHS 111 for sleep problems. CONCLUSIONS: These analyses showed marked changes in the health care attendances and prescribing for common mental health conditions across a spectrum of health care provision, with some of these changes persisting. The reasons for such changes are likely to be complex and multifactorial. The impact of the pandemic on mental health may not be fully understood for some time, and therefore, these syndromic indicators should continue to be monitored.

Adverse Events of Interest Following Influenza Vaccination in the First Season of Adjuvanted Trivalent Immunization: Retrospective Cohort Study.

BACKGROUND: Vaccination is the most effective form of prevention of seasonal influenza; the United Kingdom has a national influenza vaccination program to cover targeted population groups. Influenza vaccines are known to be associated with some common minor adverse events of interest (AEIs), but it is not known if the adjuvanted trivalent influenza vaccine (aTIV), first offered in the 2018/2019 season, would be associated with more AEIs than other types of vaccines. OBJECTIVE: We aim to compare the incidence of AEIs associated with different types of seasonal influenza vaccines offered in the 2018/2019 season. METHODS: We carried out a retrospective cohort study using computerized medical record data from the Royal College of General Practitioners Research and Surveillance Centre sentinel network database. We extracted data on vaccine exposure and consultations for European Medicines Agency-specified AEIs for the 2018/2019 influenza season. We used a self-controlled case series design; computed relative incidence (RI) of AEIs following vaccination; and compared the incidence of AEIs associated with aTIV, the quadrivalent influenza vaccine, and the live attenuated influenza vaccine. We also compared the incidence of AEIs for vaccinations that took place in a practice with those that took place elsewhere. RESULTS: A total of 1,024,160 individuals received a seasonal influenza vaccine, of which 165,723 individuals reported a total of 283,355 compatible symptoms in the 2018/2019 season. Most AEIs occurred within 7 days following vaccination, with a seasonal effect observed. Using aTIV as the reference group, the quadrivalent influenza vaccine was associated with a higher incidence of AEIs (RI 1.46, 95% CI 1.41-1.52), whereas the live attenuated influenza vaccine was associated with a lower incidence of AEIs (RI 0.79, 95% CI 0.73-0.83). No effect of vaccination setting on the incidence of AEIs was observed. CONCLUSIONS: Routine sentinel network data offer an opportunity to make comparisons between safety profiles of different vaccines. Evidence that supports the safety of newer types of vaccines may be reassuring for patients and could help improve uptake in the future.

Pfizer-BioNTech and Oxford AstraZeneca COVID-19 vaccine effectiveness and immune response amongst individuals in clinical risk groups.

Background COVID-19 vaccines approved in the UK are highly effective in general population cohorts, however, data on effectiveness amongst individuals with clinical conditions that place them at increased risk of severe disease are limited. Methods We used GP electronic health record data, sentinel virology swabbing and antibody testing within a cohort of 712 general practices across England to estimate vaccine antibody response and vaccine effectiveness against medically attended COVID-19 amongst individuals in clinical risk groups using cohort and test-negative case control designs. Findings There was no reduction in S-antibody positivity in most clinical risk groups, however reduced S-antibody positivity and response was significant in the immunosuppressed group. Reduced vaccine effectiveness against clinical disease was also noted in the immunosuppressed group; after a second dose, effectiveness was moderate (Pfizer: 59.6%, 95%CI 18.0-80.1%; AstraZeneca 60.0%, 95%CI -63.6-90.2%). Interpretation In most clinical risk groups, immune response to primary vaccination was maintained and high levels of vaccine effectiveness were seen. Reduced antibody response and vaccine effectiveness were seen after 1 dose of vaccine amongst a broad immunosuppressed group, and second dose vaccine effectiveness was moderate. These findings support maximising coverage in immunosuppressed individuals and the policy of prioritisation of this group for third doses.

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.

Adherence to the paediatric immunisation schedule in England.

Both adequate coverage and adherence to paediatric immunisation schedules are required for optimal protection against vaccine preventable diseases. We studied the timeliness of routine paediatric vaccinations according to the NHS's immunisation schedule and potential factors of schedule adherence. Immunisation data was obtained from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We collected vaccine types, doses, and dates for all routine paediatric vaccines between 2008 and 2018: DTaP/IPV/Hib/HepB, DTaP/IPV/Hib, DTaP/IPV, dTaP/IPV, Td/IPV, MMR, PCV, MenB, MenC, MenACWY, Hib/MenC, RV, HPV. Adherence to the immunisation schedule was calculated for each vaccine and dose. Differences in adherence between genders, NHS regions, and IMD quintiles were analysed. Our study included 6'257'828 vaccinations in 1'005'827 children. Seventy-five percent of first doses were administered within one (for vaccines scheduled in the first year of life) or two months (for vaccines scheduled later in life) following the recommended age, 19% too late and 6% too early. About half of the subsequent doses were given timely. The time between first and second doses was too short for 36% of vaccinations while 13% of second doses were administered too long after the first dose. Third doses were administered timely for 45%, too short for 37%, and too long for 18% of vaccinations. Differences in immunisation schedule adherence between girls and boys were negligible, except for HPV, and differences between the four main NHS regions were small. Overall, immunisation schedule adherence improved slightly with decreasing deprivation according to the Index of Multiple Deprivation. Efforts are required to improve the timeliness of paediatric vaccinations and to assure adequate protection against vaccine preventable diseases. We propose developing a compound measure combining coverage and adherence to provide a better indication of the protection against vaccine preventable diseases in a community.

Co-administration of routine paediatric vaccines in England often deviates from the immunisation schedule.

Vaccine co-administration can facilitate the introduction of new vaccines in immunisation schedules and improve coverage. We analysed real life data to quantify the extent of routine paediatric vaccine co-administrations as recommended and as never recommended in the immunisation schedule in England, and assessed factors for recommended and never recommended vaccine co-administrations. Immunisation data for all scheduled routine paediatric vaccines between 2008 and 2018 was obtained from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We included 6'257'828 doses administered to 1'005'827 children. Twenty-one percent of vaccines were given separately, 79% were co-administered. Sixty-four percent of vaccines scheduled for co-administration were co-administered as recommended while 15% were administered separately. Among all vaccine co-administrations, 75% happened as recommended in the schedule, 4% were never recommended, while 21% deviated from the schedule. Vaccine co-administration according to the schedule varied greatly between vaccines. Forty-eight percent of English children received at least one of their vaccine co-administrations not as recommended in the immunisation schedule, with 19% of children receiving none of their co-administered vaccines as recommended. Late administration of one or more vaccines increased the odds for deviated co-administrations (OR 1.60) and strongly increased the odds for never recommended co-administrations (OR 5.34). Differences between genders, NHS regions, and IMD quintiles were statistically significant but small. Suboptimal co-administration rates for routine paediatric vaccines are a missed opportunity and should be optimised by concerted public health action.

Adverse events of interest following influenza vaccination, a comparison of cell culture-based with egg-based alternatives: English sentinel network annual report paper 2019/20.

BACKGROUND: The cell-based quadrivalent influenza vaccine (QIVc) is now offered as an alternative to egg-based quadrivalent (QIVe) and adjuvanted trivalent (aTIV) influenza vaccines in the UK. While post-licensure studies show non-inferiority of cell-based vaccines, it is not known how its safety profile compares to other types of vaccines in real-world use. METHODS: We conducted a retrospective cohort study using computerised medical records from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network database. We used a self-controlled case series design and calculated the relative incidence (RI) of adverse events of interest (AEIs) over different risk periods. We then compared the RIs of AEIs within seven days of vaccination overall and between QIVc and QIVe in the 18-64 years age group, and between QIVc and aTIV in the ≥65 years age group. FINDINGS: The majority of AEIs occurred within seven days of vaccination, and a seasonal effect was observed. Using QIVc as the reference group, QIVe showed similar incidence of AEIs whereas live attenuated influenza vaccine (LAIV) and aTIV had lower incidence of AEIs. In the stratified analyses, QIVe and aTIV were associated with a 16% lower incidence of AEIs in the seven days post-vaccination in both the 18-64 years and ≥65 years age groups. INTERPRETATION: Routine sentinel network data allow comparisons of safety profiles of equally suitable seasonal influenza vaccines. The higher incidence of AEIs associated with QIVc suggest monitoring of several seasons would allow robust comparisons to be made. FUNDING: Public Health England.

An Early Warning Risk Prediction Tool (RECAP-V1) for Patients Diagnosed With COVID-19: Protocol for a Statistical Analysis Plan.

BACKGROUND: Since the start of the COVID-19 pandemic, efforts have been made to develop early warning risk scores to help clinicians decide which patient is likely to deteriorate and require hospitalization. The RECAP (Remote COVID-19 Assessment in Primary Care) study investigates the predictive risk of hospitalization, deterioration, and death of patients with confirmed COVID-19, based on a set of parameters chosen through a Delphi process performed by clinicians. We aim to use rich data collected remotely through the use of electronic data templates integrated in the electronic health systems of several general practices across the United Kingdom to construct accurate predictive models. The models will be based on preexisting conditions and monitoring data of a patient's clinical parameters (eg, blood oxygen saturation) to make reliable predictions as to the patient's risk of hospital admission, deterioration, and death. OBJECTIVE: This statistical analysis plan outlines the statistical methods to build the prediction model to be used in the prioritization of patients in the primary care setting. The statistical analysis plan for the RECAP study includes the development and validation of the RECAP-V1 prediction model as a primary outcome. This prediction model will be adapted as a three-category risk score split into red (high risk), amber (medium risk), and green (low risk) for any patient with suspected COVID-19. The model will predict the risk of deterioration and hospitalization. METHODS: After the data have been collected, we will assess the degree of missingness and use a combination of traditional data imputation using multiple imputation by chained equations, as well as more novel machine-learning approaches to impute the missing data for the final analysis. For predictive model development, we will use multiple logistic regression analyses to construct the model. We aim to recruit a minimum of 1317 patients for model development and validation. We will then externally validate the model on an independent dataset of 1400 patients. The model will also be applied for multiple different datasets to assess both its performance in different patient groups and its applicability for different methods of data collection. RESULTS: As of May 10, 2021, we have recruited 3732 patients. A further 2088 patients have been recruited through the National Health Service Clinical Assessment Service, and approximately 5000 patients have been recruited through the DoctalyHealth platform. CONCLUSIONS: The methodology for the development of the RECAP-V1 prediction model as well as the risk score will provide clinicians with a statistically robust tool to help prioritize COVID-19 patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04435041; https://clinicaltrials.gov/ct2/show/NCT04435041. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30083.

PRINCIPLE trial demonstrates scope for in-pandemic improvement in primary care antibiotic stewardship: a retrospective sentinel network cohort study.

BACKGROUND: The Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE) has provided in-pandemic evidence that azithromycin and doxycycline were not beneficial in the early primary care management of coronavirus 2019 disease (COVID-19). AIM: To explore the extent of in-pandemic azithromycin and doxycycline use, and the scope for trial findings impacting on practice. DESIGN & SETTING: Crude rates of prescribing and respiratory tract infections (RTI) in 2020 were compared with 2019, using the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). METHOD: Negative binomial models were used to compare azithromycin and doxycycline prescribing, lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), and influenza-like illness (ILI) in 2020 with 2019; reporting incident rate ratios (IRR) between years, and 95% confidence intervals (95% CI). RESULTS: Azithromycin prescriptions increased 7% in 2020 compared with 2019, whereas doxycycline decreased by 7%. Concurrently, LRTI and URTI incidence fell by over half (58.3% and 54.4%, respectively) while ILI rose slightly (6.4%). The overall percentage of RTI-prescribed azithromycin rose from 0.51% in 2019 to 0.72% in 2020 (risk difference 0.214%; 95% CI = 0.211 to 0.217); doxycycline rose from 11.86% in 2019 to 15.79% in 2020 (risk difference 3.93%; 95% CI = 3.73 to 4.14). The adjusted IRR showed azithromycin prescribing was 22% higher in 2020 (IRR = 1.22; 95% CI = 1.19 to 1.26; P<0.0001). For every unit rise in confirmed COVID-19 there was an associated 3% rise in prescription (IRR = 1.03; 95% CI = 1.02 to 1.03; P<0.0001); whereas these measures were static for doxycycline. CONCLUSION: PRINCIPLE demonstrates scope for improved antimicrobial stewardship during a pandemic.

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.

Using Primary Care Data to Report Real-World Pancreatic Cancer Survival and Symptomatology.

Pancreatic cancer is the 10th most common cancer diagnosed; despite recent advances in many areas of oncology, survival remains poor, in part owing to late diagnosis. Whilst primary care data are used widely for epidemiology and pharmacovigilance, they are less used for observing survival. In this study we extracted a pancreatic cancer cohort from a nationally representative English primary care database of electronic health records (EHRs) and reported on their symptom and mortality data. A total of 11, 649 cases were identified within the Oxford Royal College of General Practitioners (RCGP) Clinical Informatics Digital Hub network. All-cause mortality data was recorded for 4623 (39.69%). Mean age at recording of cancer diagnosis was 71.4 years (SD 12.0 years). 1-year and 5-year survival was 22.06% and 3.27% respectively. Within a multivariate model, age had a significant impact on survival; those diagnosed under the age of 60 had the longest survival, as compared to those age 60 - 79 (HR: 1.36, 95% CI: 1.20 - 1.54, p < 0.001) and 80+ (HR: 2.13, 95% CI: 1.86 - 2.44, p < 0.01). Symptomatology was examined; at any time point abdominal pain was the most commonly reported symptom present in 5271 cases (45.2%), but within the 12 months preceding diagnosis jaundice was the most common feature, present in 2587 patients (22.2%). Future studies clarifying other contributing factors on survival outcomes and patterns of symptomatology are needed; primary care EHRs provide an opportunity to evaluate real-world cancer patient cohort data.

Predicting Risk of Hospital Admission in Patients With Suspected COVID-19 in a Community Setting: Protocol for Development and Validation of a Multivariate Risk Prediction Tool.

BACKGROUND: During the pandemic, remote consultations have become the norm for assessing patients with signs and symptoms of COVID-19 to decrease the risk of transmission. This has intensified the clinical uncertainty already experienced by primary care clinicians when assessing patients with suspected COVID-19 and has prompted the use of risk prediction scores, such as the National Early Warning Score (NEWS2), to assess severity and guide treatment. However, the risk prediction tools available have not been validated in a community setting and are not designed to capture the idiosyncrasies of COVID-19 infection. OBJECTIVE: The objective of this study is to produce a multivariate risk prediction tool, RECAP-V1 (Remote COVID-19 Assessment in Primary Care), to support primary care clinicians in the identification of those patients with COVID-19 that are at higher risk of deterioration and facilitate the early escalation of their treatment with the aim of improving patient outcomes. METHODS: The study follows a prospective cohort observational design, whereby patients presenting in primary care with signs and symptoms suggestive of COVID-19 will be followed and their data linked to hospital outcomes (hospital admission and death). Data collection will be carried out by primary care clinicians in four arms: North West London Clinical Commissioning Groups (NWL CCGs), Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), Covid Clinical Assessment Service (CCAS), and South East London CCGs (Doctaly platform). The study involves the use of an electronic template that incorporates a list of items (known as RECAP-V0) thought to be associated with disease outcome according to previous qualitative work. Data collected will be linked to patient outcomes in highly secure environments. We will then use multivariate logistic regression analyses for model development and validation. RESULTS: Recruitment of participants started in October 2020. Initially, only the NWL CCGs and RCGP RSC arms were active. As of March 24, 2021, we have recruited a combined sample of 3827 participants in these two arms. CCAS and Doctaly joined the study in February 2021, with CCAS starting the recruitment process on March 15, 2021. The first part of the analysis (RECAP-V1 model development) is planned to start in April 2021 using the first half of the NWL CCGs and RCGP RSC combined data set. Posteriorly, the model will be validated with the rest of the NWL CCGs and RCGP RSC data as well as the CCAS and Doctaly data sets. The study was approved by the Research Ethics Committee on May 27, 2020 (Integrated Research Application System number: 283024, Research Ethics Committee reference number: 20/NW/0266) and badged as National Institute of Health Research Urgent Public Health Study on October 14, 2020. CONCLUSIONS: We believe the validated RECAP-V1 early warning score will be a valuable tool for the assessment of severity in patients with suspected COVID-19 in the community, either in face-to-face or remote consultations, and will facilitate the timely escalation of treatment with the potential to improve patient outcomes. TRIAL REGISTRATION: ISRCTN registry ISRCTN13953727; https://www.isrctn.com/ISRCTN13953727. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29072.

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.