Hormone replacement therapy and cancer mortality in women with 17 site-specific cancers: a cohort study using linked medical records.

BACKGROUND: There is limited evidence on the safety of Hormone Replacement Therapy (HRT) in women with cancer. Therefore, we systematically examined HRT use and cancer-specific mortality in women with 17 site-specific cancers. METHODS: Women newly diagnosed with 17 site-specific cancers from 1998 to 2019, were identified from general practitioner (GP) records, hospital diagnoses or cancer registries in Scotland, Wales and England. Breast cancer patients were excluded because HRT is contraindicated in breast cancer patients. The primary outcome was time to cancer-specific mortality. Time-dependent Cox regression models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer-specific mortality by systemic HRT use. RESULTS: The combined cancer cohorts contained 182,589 women across 17 cancer sites. Overall 7% of patients used systemic HRT after their cancer diagnosis. There was no evidence that HRT users, compared with non-users, had higher cancer-specific mortality at any cancer site. In particular, no increase was observed in common cancers including lung (adjusted HR = 0.98 95% CI 0.90, 1.07), colorectal (adjusted HR = 0.79 95% CI 0.70, 0.90), and melanoma (adjusted HR = 0.77 95% CI 0.58, 1.02). CONCLUSIONS: We observed no evidence of increased cancer-specific mortality in women with a range of cancers (excluding breast) receiving HRT.

Uptake, effectiveness and safety of COVID-19 vaccines in individuals at clinical risk due to immunosuppressive drug therapy or transplantation procedures: a population-based cohort study in England.

BACKGROUND: Immunocompromised individuals are at increased risk of severe COVID-19 outcomes, underscoring the importance of COVID-19 vaccination in this population. The lack of comprehensive real-world data on vaccine uptake, effectiveness and safety in these individuals presents a critical knowledge gap, highlighting the urgency to better understand and address the unique challenges faced by immunocompromised individuals in the context of COVID-19 vaccination. METHODS: We analysed data from 12,274,946 people in the UK aged > 12 years from 01/12/2020 to 11/04/2022. Of these, 583,541 (4.8%) were immunocompromised due to immunosuppressive drugs, organ transplants, dialysis or chemotherapy. We undertook a cohort analysis to determine COVID-19 vaccine uptake, nested case-control analyses adjusted for comorbidities and sociodemographic characteristics to determine effectiveness of vaccination against COVID-19 hospitalisation, ICU admission and death, and a self-controlled case series assessing vaccine safety for pre-specified adverse events of interest. RESULTS: Overall, 93.7% of immunocompromised individuals received at least one COVID-19 vaccine dose, with 80.4% having received three or more doses. Uptake reduced with increasing deprivation (hazard ratio [HR] 0.78 [95%CI 0.77-0.79] in the most deprived quintile compared to the least deprived quintile for the first dose). Estimated vaccine effectiveness against COVID-19 hospitalisation 2-6 weeks after the second and third doses compared to unvaccinated was 78% (95%CI 72-83) and 91% (95%CI 88-93) in the immunocompromised population, versus 85% (95%CI 83-86) and 86% (95%CI 85-89), respectively, for the general population. Results showed COVID-19 vaccines were protective against intensive care unit (ICU) admission and death in both populations, with effectiveness of over 92% against COVID-19-related death and up to 95% in reducing ICU admissions for both populations following the third dose. COVID-19 vaccines were generally safe for immunocompromised individuals, though specific doses of ChAdOx1, mRNA-1273 and BNT162b2 raised risks of specific cardiovascular/neurological conditions. CONCLUSIONS: COVID-19 vaccine uptake is high in immunocompromised individuals on immunosuppressive drug therapy or who have undergone transplantation procedures, with documented disparities by deprivation. Findings suggest that COVID-19 vaccines are protective against severe COVID-19 outcomes in this vulnerable population, and show a similar safety profile in immunocompromised individuals and the general population, despite some increased risk of adverse events. These results underscore the importance of ongoing vaccination prioritisation for this clinically at-risk population to maximise protection against severe COVID-19 outcomes.

Mental health conditions and COVID-19 vaccine outcomes: A scoping review.

OBJECTIVE: Research shows that people with a history of mental health conditions were at increased risk of COVID-19 infection, hospitalisation, and mortality. However, the relationship between mental health conditions and COVID-19 vaccine outcomes such as vaccine intention, uptake and vaccine breakthrough is not yet well-understood. METHODS: We conducted a systematic search on the topics of COVID-19 vaccine intentions, vaccine uptake, and vaccine breakthrough, in relation to mental health conditions (e.g., depression, schizophrenia), in four databases: PubMed, MEDLINE, SCOPUS, and PsychINFO, and the publication lists of Clinical Practice Research Datalink (CPRD), The Health Improvement Network (THIN), OpenSAFELY, and QResearch. Inclusion criteria focussed on studies reporting any of the aforementioned COVID-19 vaccine outcomes among people with mental health conditions. RESULTS: Of 251 publications initially identified, 32 met our inclusion criteria. Overall, the evidence is inconclusive regarding the levels of intention to accept COVID-19 vaccines among people with mental health conditions. People with mental health conditions were more likely to have lower uptake of COVID-19 vaccines, compared to people without. Common barriers to COVID-19 vaccine uptake included concerns about the safety, effectiveness, and side effects of the vaccines. Limited evidence also suggests that vaccine breakthrough may be a particular risk for those with substance use disorder. CONCLUSIONS: Evidence for the association between COVID-19 vaccine intentions and mental health conditions is mixed. Vaccine uptake might be lower in people with mental health conditions compared to people without, yielding interventions to encourage vaccine uptake in this population. Our understanding of COVID-19 vaccine breakthrough in this population also needs enhancing.

Predicting the risk of pancreatic cancer in adults with new-onset diabetes: development and internal-external validation of a clinical risk prediction model.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) recommends that people aged 60+ years with newly diagnosed diabetes and weight loss undergo abdominal imaging to assess for pancreatic cancer. More nuanced stratification could lead to enrichment of these referral pathways. METHODS: Population-based cohort study of adults aged 30-85 years at type 2 diabetes diagnosis (2010-2021) using the QResearch primary care database in England linked to secondary care data, the national cancer registry and mortality registers. Clinical prediction models were developed to estimate risks of pancreatic cancer diagnosis within 2 years and evaluated using internal-external cross-validation. RESULTS: Seven hundred and sixty-seven of 253,766 individuals were diagnosed with pancreatic cancer within 2 years. Models included age, sex, BMI, prior venous thromboembolism, digoxin prescription, HbA1c, ALT, creatinine, haemoglobin, platelet count; and the presence of abdominal pain, weight loss, jaundice, heartburn, indigestion or nausea (previous 6 months). The Cox model had the highest discrimination (Harrell's C-index 0.802 (95% CI: 0.797-0.817)), the highest clinical utility, and was well calibrated. The model's highest 1% of predicted risks captured 12.51% of pancreatic cancer cases. NICE guidance had 3.95% sensitivity. DISCUSSION: A new prediction model could have clinical utility in identifying individuals with recent onset diabetes suitable for fast-track abdominal imaging.

Safety outcomes following COVID-19 vaccination and infection in 5.1 million children in England.

The risk-benefit profile of COVID-19 vaccination in children remains uncertain. A self-controlled case-series study was conducted using linked data of 5.1 million children in England to compare risks of hospitalisation from vaccine safety outcomes after COVID-19 vaccination and infection. In 5-11-year-olds, we found no increased risks of adverse events 1-42 days following vaccination with BNT162b2, mRNA-1273 or ChAdOX1. In 12-17-year-olds, we estimated 3 (95%CI 0-5) and 5 (95%CI 3-6) additional cases of myocarditis per million following a first and second dose with BNT162b2, respectively. An additional 12 (95%CI 0-23) hospitalisations with epilepsy and 4 (95%CI 0-6) with demyelinating disease (in females only, mainly optic neuritis) were estimated per million following a second dose with BNT162b2. SARS-CoV-2 infection was associated with increased risks of hospitalisation from seven outcomes including multisystem inflammatory syndrome and myocarditis, but these risks were largely absent in those vaccinated prior to infection. We report a favourable safety profile of COVID-19 vaccination in under-18s.

Fatigue during the COVID-19 pandemic - prevalence and predictors: findings from a prospective cohort study.

The COVID-19 pandemic and consequent lockdowns had a substantial impact on mental health. Distress and fatigue are highly correlated. However, little is known about the determinants of fatigue in the general population during the pandemic. This study aimed to examine the prevalence and predictors of fatigue during the COVID-19 pandemic in the UK population. Online surveys were completed by a UK community cohort in April 2020 (wave 1), July-September 2020 (wave 2) and November-December 2020 (wave 3). In total, 3097 participants completed the wave 1 survey, and 1385 and 1087 participants (85.4% women) completed wave 2 and 3 surveys respectively. Fatigue was assessed using the Chalder Fatigue Scale at waves 2 and 3. Hair samples were provided by 827 participants (90.6% women) at wave 1 and wave 2, which were analyzed to indicate HairE (stress hormone). The mean total fatigue score during wave 2 was 14.7 (SD = 4.7), significantly higher than pre-pandemic levels observed in the community (mean difference 0.50, p = .003). At wave 2, 614 (44.3%) participants met the case definition for fatigue, only 15.6% of whom indicated that fatigue lasted for more than 6 months (suggesting it had started prior to the pandemic). Predictors of fatigue at wave 3 included being in a risk group, depression and belief in having COVID-19, which explained 23.8% of the variability in fatigue scores. Depression at wave 1 was the only significant predictor of remaining a fatigue case at wave 3. Fatigue was highly prevalent in the UK community during the COVID-19 pandemic and limited people's daily function. Depression and sociodemographic variables were significant predictors of fatigue.

Fatigue levels between July-December 2020 were higher compared to pre-pandemic levels.Predictors of fatigue levels 7-8 months later included being a clinical risk group, depression and belief in having had COVID-19.HairE was not associated with fatigue.Depression was the only significant predictor of remaining a fatigue case.

Development and validation of a new algorithm for improved cardiovascular risk prediction.

QRISK algorithms use data from millions of people to help clinicians identify individuals at high risk of cardiovascular disease (CVD). Here, we derive and externally validate a new algorithm, which we have named QR4, that incorporates novel risk factors to estimate 10-year CVD risk separately for men and women. Health data from 9.98 million and 6.79 million adults from the United Kingdom were used for derivation and validation of the algorithm, respectively. Cause-specific Cox models were used to develop models to predict CVD risk, and the performance of QR4 was compared with version 3 of QRISK, Systematic Coronary Risk Evaluation 2 (SCORE2) and atherosclerotic cardiovascular disease (ASCVD) risk scores. We identified seven novel risk factors in models for both men and women (brain cancer, lung cancer, Down syndrome, blood cancer, chronic obstructive pulmonary disease, oral cancer and learning disability) and two additional novel risk factors in women (pre-eclampsia and postnatal depression). On external validation, QR4 had a higher C statistic than QRISK3 in both women (0.835 (95% confidence interval (CI), 0.833-0.837) and 0.831 (95% CI, 0.829-0.832) for QR4 and QRISK3, respectively) and men (0.814 (95% CI, 0.812-0.816) and 0.812 (95% CI, 0.810-0.814) for QR4 and QRISK3, respectively). QR4 was also more accurate than the ASCVD and SCORE2 risk scores in both men and women. The QR4 risk score identifies new risk groups and provides superior CVD risk prediction in the United Kingdom compared with other international scoring systems for CVD risk.

Causal associations of central and peripheral risk factors with knee osteoarthritis: a longitudinal and Mendelian Randomisation study using UK Biobank data.

ABSTRACT: Our aim was to investigate relative contributions of central and peripheral mechanisms to knee osteoarthritis (OA) diagnosis and their independent causal association with knee OA. We performed longitudinal analysis using data from UK-Biobank participants. Knee OA was defined using International Classification of Diseases manual 10 codes from participants' hospital records. Central mechanisms were proxied using multisite chronic pain (MCP) and peripheral mechanisms using body mass index (BMI). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated, and proportional risk contribution (PRC) was estimated from receiver-operator-characteristic (ROC) analysis. To estimate the causal effects, we performed 2-sample multivariable Mendelian Randomisation (MR) analysis. We selected genetic instruments from the largest Genome Wide Association Study of BMI (N = 806,834) and MCP (N = 387,649) and estimated the instruments genetic associations with knee OA in the largest available dataset (62,497 cases and 333,557 control subjects). The multivariable MR was performed using modified inverse-variance weighting methods. Of the 203,410 participants, 6% developed knee OA. Both MCP (OR 1.23, 95% CI; 1.21-1.24) and BMI (1.10, 95% CI; 1.10-1.11) were associated with knee OA diagnosis. The PRC was 6.9% (95% CI; 6.7%-7.1%) for MCP and 21.9% (95% CI; 21.4%-22.5%) for BMI; the combined PRC was 38.8% (95% CI; 37.9%-39.8%). Body mass index and MCP had independent causal effects on knee OA (OR 1.76 [95% CI, 1.64-1.88] and 1.83 [95% CI, 1.54-2.16] per unit change, respectively). In conclusion, peripheral risk factors (eg, BMI) contribute more to the development of knee OA than central risk factors (eg, MCP). Peripheral and central factors are independently causal on knee OA.

Effectiveness and safety of COVID-19 vaccination in people with blood cancer.

BACKGROUND: People with blood cancer have increased risk of severe COVID-19 outcomes and poor response to vaccination. We assessed the safety and effectiveness of COVID-19 vaccines in this vulnerable group compared to the general population. METHODS: Individuals aged ≥12 years as of 1st December 2020 in the QResearch primary care database were included. We assessed adjusted COVID-19 vaccine effectiveness (aVE) against COVID-19-related hospitalisation and death in people with blood cancer using a nested matched case-control study. Using the self-controlled case series methodology, we compared the risk of 56 pre-specified adverse events within 1-28 days of a first, second or third COVID-19 vaccine dose in people with and without blood cancer. FINDINGS: The cohort comprised 12,274,948 individuals, of whom 81,793 had blood cancer. COVID-19 vaccines were protective against COVID-19-related hospitalisation and death in people with blood cancer, although they were less effective, particularly against COVID-19-related hospitalisation, compared to the general population. In the blood cancer population, aVE against COVID-19-related hospitalisation was 64% (95% confidence interval [CI] 48%-75%) 14-41 days after a third dose, compared to 80% (95% CI 78%-81%) in the general population. Against COVID-19-related mortality, aVE was >80% in people with blood cancer 14-41 days after a second or third dose. We found no significant difference in risk of adverse events 1-28 days after any vaccine dose between people with and without blood cancer. INTERPRETATION: Our study provides robust evidence which supports the use of COVID-19 vaccinations for people with blood cancer.

Vaginal Estrogen Therapy Use and Survival in Females With Breast Cancer.

Importance: Genitourinary syndrome of menopause can be treated with vaginal estrogen therapy. However, there are concerns about the safety of vaginal estrogen therapy in patients with breast cancer. Objective: To determine whether the risk of breast cancer-specific mortality was higher in females with breast cancer who used vaginal estrogen therapy vs females with breast cancer who did not use hormone replacement therapy (HRT). Design, Setting, and Participants: This cohort study analyzed 2 large cohorts, one each in Scotland and Wales, of females aged 40 to 79 years with newly diagnosed breast cancer. These population-based cohorts were identified from national cancer registry records from 2010 to 2017 in Scotland and from 2000 to 2016 in Wales and were followed up for breast cancer-specific mortality until 2020. Females were excluded if they had a previous cancer diagnosis (except nonmelanoma skin cancer). Data analysis was performed between August 2022 and August 2023. Exposure: Use of vaginal estrogen therapy, including vaginal tablets and creams, was ascertained from pharmacy dispensing records of the Prescribing Information System for the Scotland cohort and from general practice prescription records for the Wales cohort. Main Outcomes and Measures: The primary outcome was time to breast cancer-specific mortality, which was obtained from national mortality records. Time-dependent Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs for breast cancer-specific mortality, comparing vaginal estrogen therapy users with HRT nonusers and adjusting for confounders, including cancer stage and grade. Results: The 2 cohorts comprised 49 237 females with breast cancer (between 40 and 79 years of age) and 5795 breast cancer-specific deaths. Five percent of patients with breast cancer used vaginal estrogen therapy after breast cancer diagnosis. In vaginal estrogen therapy users compared with HRT nonusers, there was no evidence of a higher risk of breast cancer-specific mortality in the pooled fully adjusted model (HR, 0.77; 95% CI, 0.63-0.94). Conclusions and Relevance: Results of this study showed no evidence of increased early breast cancer-specific mortality in patients who used vaginal estrogen therapy compared with patients who did not use HRT. This finding may provide some reassurance to prescribing clinicians and support the guidelines suggesting that vaginal estrogen therapy can be considered in patients with breast cancer and genitourinary symptoms.

Dynamic updating of clinical survival prediction models in a changing environment.

BACKGROUND: Over time, the performance of clinical prediction models may deteriorate due to changes in clinical management, data quality, disease risk and/or patient mix. Such prediction models must be updated in order to remain useful. In this study, we investigate dynamic model updating of clinical survival prediction models. In contrast to discrete or one-time updating, dynamic updating refers to a repeated process for updating a prediction model with new data. We aim to extend previous research which focused largely on binary outcome prediction models by concentrating on time-to-event outcomes. We were motivated by the rapidly changing environment seen during the COVID-19 pandemic where mortality rates changed over time and new treatments and vaccines were introduced. METHODS: We illustrate three methods for dynamic model updating: Bayesian dynamic updating, recalibration, and full refitting. We use a simulation study to compare performance in a range of scenarios including changing mortality rates, predictors with low prevalence and the introduction of a new treatment. Next, the updating strategies were applied to a model for predicting 70-day COVID-19-related mortality using patient data from QResearch, an electronic health records database from general practices in the UK. RESULTS: In simulated scenarios with mortality rates changing over time, all updating methods resulted in better calibration than not updating. Moreover, dynamic updating outperformed ad hoc updating. In the simulation scenario with a new predictor and a small updating dataset, Bayesian updating improved the C-index over not updating and refitting. In the motivating example with a rare outcome, no single updating method offered the best performance. CONCLUSIONS: We found that a dynamic updating process outperformed one-time discrete updating in the simulations. Bayesian updating offered good performance overall, even in scenarios with new predictors and few events. Intercept recalibration was effective in scenarios with smaller sample size and changing baseline hazard. Refitting performance depended on sample size and produced abrupt changes in hazard ratio estimates between periods.

Seasonal trends in antidepressant prescribing, depression, anxiety and self-harm in adolescents and young adults: an open cohort study using English primary care data.

BACKGROUND: There is an increasing demand for mental health services for young people, which may vary across the year. OBJECTIVE: To determine whether there are seasonal patterns in primary care antidepressant prescribing and mental health issues in adolescents and young adults. METHODS: This cohort study used anonymised electronic health records from general practices in England contributing to QResearch. It included 5 081 263 males and females aged 14-18 (adolescents), 19-23 and 24-28 years between 2006 and 2019. The incidence rates per 1000 person-years and the incidence rate ratios (IRRs) were calculated for the first records of a selective serotonin reuptake inhibitor (SSRI) prescription, depression, anxiety and self-harm. The IRRs were adjusted for year, region, deprivation, ethnic group and number of working days. FINDINGS: There was an increase in SSRI prescribing, depression and anxiety incidence in male and female adolescents in the autumn months (September-November) that was not seen in older age groups. The IRRs for SSRI prescribing for adolescents peaked in November (females: 1.75, 95% CI 1.67 to 1.83, p<0.001; males: 1.72, 95% CI 1.61 to 1.84, p<0.001, vs in January) and for depression (females: 1.29, 95% CI 1.25 to 1.33, p<0.001; males: 1.29, 95% CI 1.23 to 1.35, p<0.001). Anxiety peaked in November for females aged 14-18 years (1.17, 95% CI 1.13 to 1.22, p<0.001) and in September for males (1.19, 95% CI 1.12 to 1.27, p<0.001). CONCLUSIONS: There were higher rates of antidepressant prescribing and consultations for depression and anxiety at the start of the school year among adolescents. CLINICAL IMPLICATIONS: Support around mental health issues from general practitioners and others should be focused during autumn.

Causal association between subtypes of osteoarthritis and common comorbidities: A Mendelian randomisation study.

Objective: To investigate the causal association between Osteoarthritis (OA) and five comorbidities: depression, tiredness, multisite chronic pain, irritable bowel syndrome (IBS) and gout. Design: This study used two-sample Mendelian Randomisation (MR). To select the OA genetic instruments, we used data from the largest recent genome-wide association study (GWAS) of OA (GO Consortium), with a focus on OA of the knee (62,497 cases, 333,557 controls), hip (35,445 cases, 316,943 controls) and hand (20,901 cases, 282,881 controls). Genetic associations for comorbidities were selected from GWAS for depression (246,363 cases, 561,190 controls), tiredness (449,019 participants), multisite chronic pain (387,649 participants), IBS (53,400 cases, 433,201 controls) and gout (6543 cases, 456,390 controls). We performed a bidirectional MR analysis using the inverse variance weighted method, for both joint specific and overall OA. Results: Hip OA had a causal effect on multisite chronic pain (per unit change 0.02, 95% CI 0.01 to 0.04). Multisite chronic pain had a causal effect on knee (odd ratio (OR) 2.74, 95% CI 2.20 to 3.41), hip (OR 2.12, 95% CI 1.54 to 2.92), hand (OR 2.24, 95% CI 1.59 to 3.16) and overall OA (OR 2.44, 95% CI, 2.06 to 2.86). In addition, depression and tiredness had causal effects on knee and hand, but not hip, OA. Conclusions: Apart from Hip OA to multisite chronic pain, other joint OA did not have causal effects on these comorbidities. In contrast, multisite chronic pain had a causal effect on any painful OA.

Development and validation of a novel risk prediction algorithm to estimate 10-year risk of oesophageal cancer in primary care: prospective cohort study and evaluation of performance against two other risk prediction models.

Background: Methods to identify patients at increased risk of oesophageal cancer are needed to better identify those for targeted screening. We aimed to derive and validate novel risk prediction algorithms (CanPredict) to estimate the 10-year risk of oesophageal cancer and evaluate performance against two other risk prediction models. Methods: Prospective open cohort study using routinely collected data from 1804 QResearch® general practices. We used 1354 practices (12.9 M patients) to develop the algorithm. We validated the algorithm in 450 separate practices from QResearch (4.12 M patients) and 355 Clinical Practice Research Datalink (CPRD) practices (2.53 M patients). The primary outcome was an incident diagnosis of oesophageal cancer found in GP, mortality, hospital, or cancer registry data. Patients were aged 25-84 years and free of oesophageal cancer at baseline. Cox proportional hazards models were used with prediction selection to derive risk equations. Risk factors included age, ethnicity, Townsend deprivation score, body mass index (BMI), smoking, alcohol, family history, relevant co-morbidities and medications. Measures of calibration, discrimination, sensitivity, and specificity were calculated in the validation cohorts. Finding: There were 16,384 incident cases of oesophageal cancer in the derivation cohort (0.13% of 12.9 M). The predictors in the final algorithms were: age, BMI, Townsend deprivation score, smoking, alcohol, ethnicity, Barrett's oesophagus, hiatus hernia, H. pylori infection, use of proton pump inhibitors, anaemia, lung and blood cancer (with breast cancer in women). In the QResearch validation cohort in women the explained variation (R2) was 57.1%; Royston's D statistic 2.36 (95% CI 2.26-2.46); C statistic 0.859 (95% CI 0.849-0.868) and calibration was good. Results were similar in men. For the 20% at highest predicted risk, the sensitivity was 76%, specificity was 80.1% and the observed risk at 10 years was 0.76%. The results from the CPRD validation were similar. Interpretation: We have developed and validated a novel prediction algorithm to quantify the absolute risk of oesophageal cancer. The CanPredict algorithms could be used to identify high risk patients for targeted screening. Funding: Innovate UK and CRUK (grant 105857).

Healthcare utilisation and mortality in people with osteoarthritis in the UK: findings from a national primary care database.

BACKGROUND: The burden of osteoarthritis (OA) in UK primary care has not been investigated thoroughly. AIM: To estimate healthcare use and mortality in people with OA (overall and joint specific). DESIGN AND SETTING: A matched cohort study of adults with an incident diagnosis of OA in primary care were selected for the study using UK national Clinical Practice Research Datalink (CPRD) electronic records. METHOD: Healthcare utilisation was measured as the annual average number of primary care consultations and admissions to hospital after the index date for any cause and all-cause mortality data in 221 807 people with OA and an equal number of controls (with no OA diagnosis) who were matched to the case patients by age (standard deviation 2 years), sex, practice, and year of registration. The associations between OA and healthcare utilisation and all-cause mortality were estimated using multinomial logistic regression and Cox regression, respectively, adjusting for covariates. RESULTS: The mean age of the study population was 61 years and 58% were female. In the OA group, the median number of primary care consultations per year after the index date was 10.91 compared with 9.43 in the non-OA control group (P = 0.001) OA was associated with an increased risk of GP consultation and admission to hospital. The adjusted hazard ratio for all-cause mortality was 1.89 (95% confidence interval [CI] = 1.85 to 1.93) for any OA, 2.09 (95% CI = 2.01 to 2.19) for knee OA, 2.08 (95% CI = 1.95 to 2.21) for hip OA, and 1.80 (95% CI = 1.58 to 2.06) for wrist/hand OA, compared with the respective non-OA control group. CONCLUSION: People with OA had increased rates of GP consultations, admissions to hospital, and all-cause mortality that varied across joint sites.

Frequency and impact of medication reviews for people aged 65 years or above in UK primary care: an observational study using electronic health records.

BACKGROUND: Medication reviews in primary care provide an opportunity to review and discuss the safety and appropriateness of a person's medicines. However, there is limited evidence about access to and the impact of routine medication reviews for older adults in the general population, particularly in the UK. We aimed to quantify the proportion of people aged 65 years and over with a medication review recorded in 2019 and describe changes in the numbers and types of medicines prescribed following a review. METHODS: We used anonymised primary care electronic health records from the UK's Clinical Practice Research Datalink (CPRD GOLD) to define a population of people aged 65 years or over in 2019. We counted people with a medication review record in 2019 and used Cox regression to estimate associations between demographic characteristics, diagnoses, and prescribed medicines and having a medication review. We used linear regression to compare the number of medicines prescribed as repeat prescriptions in the three months before and after a medication review. Specifically, we compared the 'prescription count' - the maximum number of different medicines with overlapping prescriptions people had in each period. RESULTS: Of 591,726 people prescribed one or more medicines at baseline, 305,526 (51.6%) had a recorded medication review in 2019. Living in a care home (hazard ratio 1.51, 95% confidence interval 1.40-1.62), medication review in the previous year (1.83, 1.69-1.98), and baseline prescription count (e.g. 5-9 vs 1 medicine 1.41, 1.37-1.46) were strongly associated with having a medication review in 2019. Overall, the prescription count tended to increase after a review (mean change 0.13 medicines, 95% CI 0.12-0.14). CONCLUSIONS: Although medication reviews were commonly recorded for people aged 65 years or over, there was little change overall in the numbers and types of medicines prescribed following a review. This study did not examine whether the prescriptions were appropriate or other metrics, such as dose or medicine changes within the same class. However, by examining the impact of medication reviews before the introduction of structured medication review requirements in England in 2020, it provides a useful benchmark which these new reviews can be compared with.

Risk prediction of covid-19 related death or hospital admission in adults testing positive for SARS-CoV-2 infection during the omicron wave in England (QCOVID4): cohort study.

OBJECTIVES: To derive and validate risk prediction algorithms (QCOVID4) to estimate the risk of covid-19 related death and hospital admission in people with a positive SARS-CoV-2 test result during the period when the omicron variant of the virus was predominant in England, and to evaluate performance compared with a high risk cohort from NHS Digital. DESIGN: Cohort study. SETTING: QResearch database linked to English national data on covid-19 vaccinations, SARS-CoV-2 test results, hospital admissions, and cancer and mortality data, 11 December 2021 to 31 March 2022, with follow-up to 30 June 2022. PARTICIPANTS: 1.3 million adults in the derivation cohort and 0.15 million adults in the validation cohort, aged 18-100 years, with a positive test result for SARS-CoV-2 infection. MAIN OUTCOME MEASURES: Primary outcome was covid-19 related death and secondary outcome was hospital admission for covid-19. Risk equations with predictor variables were derived from models fitted in the derivation cohort. Performance was evaluated in a separate validation cohort. RESULTS: Of 1 297 922 people with a positive test result for SARS-CoV-2 infection in the derivation cohort, 18 756 (1.5%) had a covid-19 related hospital admission and 3878 (0.3%) had a covid-19 related death during follow-up. The final QCOVID4 models included age, deprivation score and a range of health and sociodemographic factors, number of covid-19 vaccinations, and previous SARS-CoV-2 infection. The risk of death related to covid-19 was lower among those who had received a covid-19 vaccine, with evidence of a dose-response relation (42% risk reduction associated with one vaccine dose and 92% reduction with four or more doses in men). Previous SARS-CoV-2 infection was associated with a reduction in the risk of covid-19 related death (49% reduction in men). The QCOVID4 algorithm for covid-19 explained 76.0% (95% confidence interval 73.9% to 78.2%) of the variation in time to covid-19 related death in men with a D statistic of 3.65 (3.43 to 3.86) and Harrell's C statistic of 0.970 (0.962 to 0.979). Results were similar for women. QCOVID4 was well calibrated. QCOVID4 was substantially more efficient than the NHS Digital algorithm for correctly identifying patients at high risk of covid-19 related death. Of the 461 covid-19 related deaths in the validation cohort, 333 (72.2%) were in the QCOVID4 high risk group and 95 (20.6%) in the NHS Digital high risk group. CONCLUSION: The QCOVID4 risk algorithm, modelled from data during the period when the omicron variant of the SARS-CoV-2 virus was predominant in England, now includes vaccination dose and previous SARS-CoV-2 infection, and predicted covid-19 related death among people with a positive test result. QCOVID4 more accurately identified individuals at the highest levels of absolute risk for targeted interventions than the approach adopted by NHS Digital. QCOVID4 performed well and could be used for targeting treatments for covid-19 disease.

Disparities in care and outcomes for primary liver cancer in England during 2008-2018: a cohort study of 8.52 million primary care population using the QResearch database.

Background: Liver cancer has one of the fastest rising incidence and mortality rates among all cancers in the UK, but it receives little attention. This study aims to understand the disparities in epidemiology and clinical pathways of primary liver cancer and identify the gaps for early detection and diagnosis of liver cancer in England. Methods: This study used a dynamic English primary care cohort of 8.52 million individuals aged ≥25 years in the QResearch database during 2008-2018, followed up to June 2021. The crude and age-standardised incidence rates, and the observed survival duration were calculated by sex and three liver cancer subtypes, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CCA), and other specified/unspecified primary liver cancer. Regression models were used to investigate factors associated with an incident diagnosis of liver cancer, emergency presentation, late stage at diagnosis, receiving treatments, and survival duration after diagnosis by subtype. Findings: 7331 patients were diagnosed with primary liver cancer during follow-up. The age-standardised incidence rates increased over the study period, particularly for HCC in men (increased by 60%). Age, sex, socioeconomic deprivation, ethnicity, and geographical regions were all significantly associated with liver cancer incidence in the English primary care population. People aged ≥80 years were more likely to be diagnosed through emergency presentation and in late stages, less likely to receive treatments and had poorer survival than those aged <60 years. Men had a higher risk of being diagnosed with liver cancer than women, with a hazard ratio (HR) of 3.9 (95% confidence interval 3.6-4.2) for HCC, 1.2 (1.1-1.3) for CCA, and 1.7 (1.5-2.0) for other specified/unspecified liver cancer. Compared with white British, Asians and Black Africans were more likely to be diagnosed with HCC. Patients with higher socioeconomic deprivation were more likely to be diagnosed through the emergency route. Survival rates were poor overall. Patients diagnosed with HCC had better survival rates (14.5% at 10-year survival, 13.1%-16.0%) compared to CCA (4.4%, 3.4%-5.6%) and other specified/unspecified liver cancer (12.5%, 10.1%-15.2%). For 62.7% of patients with missing/unknown stage in liver cancer, their survival outcomes were between those diagnosed in Stages III and IV. Interpretation: This study provides an overview of the current epidemiology and the disparities in clinical pathways of primary liver cancer in England between 2008 and 2018. A complex public health approach is needed to tackle the rapid increase in incidence and the poor survival of liver cancer. Further studies are urgently needed to address the gaps in early detection and diagnosis of liver cancer in England. Funding: The Early Detection of Hepatocellular Liver Cancer (DeLIVER) project is funded by Cancer Research UK (Early Detection Programme Award, grant reference: C30358/A29725).