PURPOSE: To illustrate the interest in using interrupted time series (ITS) methods, this study evaluated the impact of the UK MHRA’s March 2019 Risk Minimisation Measures (RMM) on fluoroquinolone usage. METHODS: Monthly and quarterly fluoroquinolone use incidence rates from 2012 to 2022 were analysed across hospital care (Barts Health NHS Trust), primary care (Clinical Practice Research Datalink (CPRD) Aurum and CPRD GOLD), and linked records from both settings (East Scotland). Rates were stratified by age (19-59 and = 60 years old). Seasonality-adjusted segmented regression and ARIMA models were employed to model quarterly and monthly rates, respectively. RESULTS: Post-RMM, with segmented regression, both age groups in Barts Health experienced nearly complete reductions (> 99%); CPRD Aurum saw 20.19% (19-59) and 19.29% (  =  60) reductions; no significant changes in CPRD GOLD; East Scotland had 45.43% (19-59) and 41.47% (  =  60) decreases. Slope analysis indicated increases for East Scotland (19-59) and both CPRD Aurum groups, but a decrease for CPRD GOLD’s  =  60; ARIMA detected significant step changes in CPRD GOLD not identified by segmented regression and noted a significant slope increase in Barts Health’s 19-59 group. Both models showed no post-modelling autocorrelations across databases, yet Barts Health’s residuals were non-normally distributed with non-constant variance. CONCLUSIONS: Both segmented regression and ARIMA confirmed the reduction of fluoroquinolones use after RMM across four different UK primary care and hospital databases. Model diagnostics showed good performance in eliminating residual autocorrelation for both methods. However, diagnostics for hospital databases with low incident use revealed the presence of heteroscedasticity and non-normal white noise using both methods.

Background: Lung cancer is the leading cause of cancer-associated mortality worldwide. In the United Kingdom (UK), there has been a major reduction in smoking, the leading risk factor for lung cancer. Therefore, an up-to-date assessment of the trends of lung cancer is required in the UK. This study aims to describe lung cancer burden and trends in terms of incidence, prevalence, and survival from 2000-2021, using two UK primary care databases.Methods: We performed a population-based cohort study using the UK primary care Clinical Practice Research Datalink (CPRD) GOLD database, compared with CPRD Aurum. Participants aged 18+ years, with 1-year of prior data availability, were included. We estimated lung cancer incidence rates (IRs), period prevalence (PP), and survival at 1, 5 and 10 years after diagnosis using the Kaplan-Meier (KM) method. Results: Overall, 11,388,117 participants, with 45,563 lung cancer cases were studied. The IR of lung cancer was 52.0 [95% confidence interval (CI): 51.5 to 52.5] per 100,000 person-years, with incidence increasing from 2000 to 2021. Females aged over 50 years of age showed increases in incidence over the study period, ranging from increases of 8 to 123 per 100,000 person-years, with the greatest increase in females aged 80-89 years. Alternatively, for males, only cohorts aged over 80 years showed increases in incidence over the study period. The highest IR was observed in people aged 80-89 years. PP in 2021 was 0.18%, with the largest rise seen in participants aged over 60 years. Median survival post-diagnosis increased from 6.6 months in those diagnosed between 2000-2004 to 10.0 months between 2015-2019. Both short and long-term survival was higher in younger cohorts, with 82.7% 1-year survival in those aged 18-29 years, versus 24.2% in the age 90+ years cohort. Throughout the study period, survival was longer in females, with a larger increase in survival over time than in males. Conclusions: The incidence and prevalence of lung cancer diagnoses in the UK have increased, especially in female and older populations, with a small increase in median survival. This study will enable future comparisons of overall disease burden, so the overall impact may be seen

IMPORTANCE: Incidence, prevalence, and survival are pertinent measures to inform the management and provision of prostate cancer care. OBJECTIVE: To calculate the incidence, prevalence, and survival rates for prostate cancer in the UK from 2000 to 2021. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study uses routinely collected primary care data from the UK. Male patients aged 18 years or older with at least 1 year of history registered in Clinical Practice Research Datalink (CPRD) GOLD or Aurum were included. Data were analyzed from January 2023 to March 2024. MAIN OUTCOMES AND MEASURES: Prostate cancer incidence rates (IR), period prevalence (PP), and 1-, 5-, and 10-year survival after diagnosis between 2000 and 2021, stratified by age and calendar years. RESULTS: This study included 64?925 and 133?200 patients with prostate cancer in CPRD GOLD and Aurum, respectively, with a median age of 72 (65-78) years. The overall IR of prostate cancer was 151.7 (95% CI, 150.6 to 152.9) per 100?000 person-years in GOLD to 153.1 (95% CI, 152.3 to 153.9) per 100?000 person-years for Aurum and increased with age. The incidence of prostate cancer increased from 109 per 100 000 person-years in 2000 to 159 per 100 000 person-years in 2021. Peaks of incidence occurred in 2004 and 2018, before a decline in 2020. PP increased 3.5 times over the study period for both databases, from 0.4% in 2000 to 1.4% in 2021. IR and PP were highest in those aged 80 to 89 years. Median (95% CI) survival was similar in both databases (GOLD: 10.9 [95% CI, 10.7-11.1] years and Aurum: 11.1 [95% CI, 11.0-11.2] years). Survival at 1, 5, and 10 years after diagnosis were 93.4% (95% CI, 93.2%-93.6%), 71.8% (95% CI, 71.4%-72.2%), 53.2% (95% CI, 52.6%-53.7%) in GOLD and 93.9% (95% CI, 93.7%-94.0%), 72.7% (95% CI, 72.5%-73.0%), 53.7% (95% CI, 53.3%-54.1%) in AURUM, respectively. Survival increased over time: 1-year survival was 94.8% (95% CI, 94.5%-95.2%) in those diagnosed between 2015 to 2019 compared with 90.8% (95% CI, 90.2%-91.3%) from 2000 to 2004; 5-year survival improved from 65.3% (95% CI, 64.4%-66.3%) from 2000 to 2004 to 75.3% (95% CI, 74.4%-76.3%) in 2015 to 2019. CONCLUSIONS AND RELEVANCE: In this population-based cohort study, incidence and prevalence increased with older age, with high survival rates reflecting a high burden of disease, particularly in the management of cancer survivorship in an aging population. Health care systems should consider this when managing the increasing numbers of people with prevalent prostate cancer.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head clinical trials. OBJECTIVES: The aim of this study was to compare the cardiovascular effectiveness of SGLT2is, GLP-1 RAs, dipeptidyl peptidase-4 inhibitors (DPP4is), and clinical sulfonylureas (SUs) as second-line antihyperglycemic agents in T2DM. METHODS: Across the LEGEND-T2DM (Large-Scale Evidence Generation and Evaluation Across a Network of Databases for Type 2 Diabetes Mellitus) network, 10 federated international data sources were included, spanning 1992 to 2021. In total, 1,492,855 patients with T2DM and cardiovascular disease (CVD) on metformin monotherapy were identified who initiated 1 of 4 second-line agents (SGLT2is, GLP-1 RAs, DPP4is, or SUs). Large-scale propensity score models were used to conduct an active-comparator target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, on-treatment Cox proportional hazards models were fit for 3-point MACE (myocardial infarction, stroke, and death) and 4-point MACE (3-point MACE plus heart failure hospitalization) risk and HR estimates were combined using random-effects meta-analysis. RESULTS: Over 5.2 million patient-years of follow-up and 489 million patient-days of time at risk, patients experienced 25,982 3-point MACE and 41,447 4-point MACE. SGLT2is and GLP-1 RAs were associated with lower 3-point MACE risk than DPP4is (HR: 0.89 [95% CI: 0.79-1.00] and 0.83 [95% CI: 0.70-0.98]) and SUs (HR: 0.76 [95% CI: 0.65-0.89] and 0.72 [95% CI: 0.58-0.88]). DPP4is were associated with lower 3-point MACE risk than SUs (HR: 0.87; 95% CI: 0.79-0.95). The pattern for 3-point MACE was also observed for the 4-point MACE outcome. There were no significant differences between SGLT2is and GLP-1 RAs for 3-point or 4-point MACE (HR: 1.06 [95% CI: 0.96-1.17] and 1.05 [95% CI: 0.97-1.13]). CONCLUSIONS: In patients with T2DM and CVD, comparable cardiovascular risk reduction was found with SGLT2is and GLP-1 RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of SGLT2is and GLP-1 RAs should be prioritized as second-line agents in those with established CVD.