Time Series Methods to Assess the Impact of Regulatory Action: A Study of UK Primary Care and Hospital Data on the Use of Fluoroquinolones.

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% ( ≥ $$ \ge $$ 60) reductions; no significant changes in CPRD GOLD; East Scotland had 45.43% (19-59) and 41.47% ( ≥ $$ \ge $$ 60) decreases. Slope analysis indicated increases for East Scotland (19-59) and both CPRD Aurum groups, but a decrease for CPRD GOLD's ≥ $$ \ge $$ 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.

Drug utilization analysis of osteoporosis medications in seven European electronic health databases.

We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had hypertension. There was suboptimal persistence particularly for oral medications. Our findings would be useful to healthcare providers to focus their resources on improving persistence to specific osteoporosis treatments. PURPOSE: To characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns. METHODS: We investigated the treatment patterns of bisphosphonates, denosumab, teriparatide, and selective estrogen receptor modulators (SERMs) in seven European databases in the United Kingdom, Italy, the Netherlands, Denmark, Spain, and Germany. In this cohort study, we included adults aged ≥ 18 years, with ≥ 1 year of registration in the respective databases, who were new users of the osteoporosis medications. The study period was between 01 January 2018 to 31 January 2022. RESULTS: Overall, patients were most commonly initiated on alendronate. Persistence decreased over time across all medications and databases, ranging from 52-73% at 6 months to 29-53% at 12 months for alendronate. For other oral bisphosphonates, the proportion of persistent users was 50-66% at 6 months and decreased to 30-44% at 12 months. For SERMs, the proportion of persistent users at 6 months was 40-73% and decreased to 25-59% at 12 months. For parenteral treatment groups, the proportions of persistence with denosumab were 50-85% (6 month), 30-63% (12 month) and with teriparatide 40-75% (6 month) decreasing to 21-54% (12 month). Switching occurred most frequently in the alendronate group (2.8-5.8%) and in the teriparatide group (7.1-14%). Switching typically occurred in the first 6 months and decreased over time. Patients in the alendronate group most often switched to other oral or intravenous bisphosphonates and denosumab. CONCLUSION: Our results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare.

Safety outcomes of selective serotonin reuptake inhibitors in adolescent attention-deficit/hyperactivity disorder with comorbid depression: the ASSURE study.

BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is related to depressive disorder, and adolescents with both present poor outcomes. However, evidence for the safety of concomitantly using a methylphenidate (MPH) and a selective serotonin reuptake inhibitor (SSRI) among adolescent ADHD patients is limited, a literature gap aimed to address through this investigation. METHODS: We conducted a new-user cohort study using a nationwide claims database in South Korea. We identified a study population as adolescents who were diagnosed both ADHD and depressive disorder. MPH-only users were compared with patients who prescribed both a SSRI and a MPH. Fluoxetine and escitalopram users were also compared to find a preferable treatment option. Thirteen outcomes including neuropsychiatric, gastrointestinal, and other events were assessed, taking respiratory tract infection as a negative control outcome. We matched the study groups using a propensity score and used the Cox proportional hazard model to calculate the hazard ratio. Subgroup and sensitivity analyses were conducted in various epidemiologic settings. RESULTS: The risks of all the outcomes between the MPH-only and SSRI groups were not significantly different. Regarding SSRI ingredients, the risk of tic disorder was significantly lower in the fluoxetine group than the escitalopram group [HR 0.43 (0.25-0.71)]. However, there was no significant difference in other outcomes between the fluoxetine and escitalopram groups. CONCLUSION: The concomitant use of MPHs and SSRIs showed generally safe profiles in adolescent ADHD patients with depression. Most of the differences between fluoxetine and escitalopram, except those concerning tic disorder, were not significant.

Electronic health records (EHRs) in clinical research and platform trials: Application of the innovative EHR-based methods developed by EU-PEARL.

OBJECTIVE: Electronic Health Record (EHR) systems are digital platforms in clinical practice used to collect patients' clinical information related to their health status and represents a useful storage of real-world data. EHRs have a potential role in research studies, in particular, in platform trials. Platform trials are innovative trial designs including multiple trial arms (conducted simultaneously and/or sequentially) on different treatments under a single master protocol. However, the use of EHRs in research comes with important challenges such as incompleteness of records and the need to translate trial eligibility criteria into interoperable queries. In this paper, we aim to review and to describe our proposed innovative methods to tackle some of the most important challenges identified. This work is part of the Innovative Medicines Initiative (IMI) EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project's work package 3 (WP3), whose objective is to deliver tools and guidance for EHR-based protocol feasibility assessment, clinical site selection, and patient pre-screening in platform trials, investing in the building of a data-driven clinical network framework that can execute these complex innovative designs for which feasibility assessments are critically important. METHODS: ISO standards and relevant references informed a readiness survey, producing 354 criteria with corresponding questions selected and harmonised through a 7-round scoring process (0-1) in stakeholder meetings, with 85% of consensus being the threshold of acceptance for a criterium/question. ATLAS cohort definition and Cohort Diagnostics were mainly used to create the trial feasibility eligibility (I/E) criteria as executable interoperable queries. RESULTS: The WP3/EU-PEARL group developed a readiness survey (eSurvey) for an efficient selection of clinical sites with suitable EHRs, consisting of yes-or-no questions, and a set-up of interoperable proxy queries using physicians' defined trial criteria. Both actions facilitate recruiting trial participants and alignment between study costs/timelines and data-driven recruitment potential. CONCLUSION: The eSurvey will help create an archive of clinical sites with mature EHR systems suitable to participate in clinical trials/platform trials, and the interoperable proxy queries of trial eligibility criteria will help identify the number of potential participants. Ultimately, these tools will contribute to the production of EHR-based protocol design.

Risk of adverse events following the initiation of antihypertensives in older people with complex health needs: a self-controlled case series in the United Kingdom.

BACKGROUND: We assessed the risk of adverse events-severe acute kidney injury (AKI), falls and fractures-associated with use of antihypertensives in older patients with complex health needs (CHN). SETTING: UK primary care linked to inpatient and mortality records. METHODS: The source population comprised patients aged >65, with ≥1 year of registration and unexposed to antihypertensives in the year before study start. We identified three cohorts of patients with CHN, namely, unplanned hospitalisations, frailty (electronic frailty index deficit count ≥3) and polypharmacy (prescription of ≥10 medicines). Patients in any of these cohorts were included in the CHN cohort. We conducted self-controlled case series for each cohort and outcome (AKI, falls, fractures). Incidence rate ratios (IRRs) were estimated by dividing event rates (i) during overall antihypertensive exposed patient-time over unexposed patient-time; and (ii) in the first 30 days after treatment initiation over unexposed patient-time. RESULTS: Among 42,483 patients in the CHN cohort, 7,240, 5,164 and 450 individuals had falls, fractures or AKI, respectively. We observed an increased risk for AKI associated with exposure to antihypertensives across all cohorts (CHN: IRR 2.36 [95% CI: 1.68-3.31]). In the 30 days post-antihypertensive treatment initiation, a 35-50% increased risk for falls was found across all cohorts and increased fracture risk in the frailty cohort (IRR 1.38 [1.03-1.84]). No increased risk for falls/fractures was associated with continuation of antihypertensive treatment or overall use. CONCLUSION: Treatment with antihypertensives in older patients was associated with increased risk of AKI and transiently elevated risk of falls in the 30 days after starting antihypertensive therapy.

Facilitators and barriers to medication adherence with adjuvant endocrine therapy in women with breast cancer: a structural equation modelling approach.

PURPOSE: To identify a structure to explain the relationship between socio-clinico factors, necessity-concerns beliefs, and perceived barriers to adherence with adjuvant endocrine therapy (AET) amongst women with breast cancer. METHODS: Participants were 244 patients with early-stage breast cancer recruited from two tertiary hospitals from May 2015 to December 2018 who completed questionnaires on medication adherence (Simplified Medication Adherence Questionnaire), necessity-concerns beliefs (Beliefs about Medicine Questionnaire), and barriers to adherence (Adherence Starts with Knowledge Questionnaire). Socio-clinico variables were collected via interview and medical records review. Structural equation modelling was applied to examine the relationships between these variables and possible mediating effects of necessity-concerns beliefs on adherence to AET. RESULTS: The median age of the study participants was 61 (range 32-80) years and the median duration on AET was 1.6 (IQR 1.2-2.6) years. Adherence was positively associated with age (ß = 0.145, 95% CI: 0.011 to 0.279, p = 0.034) and negatively associated with barriers (ß = - 0.381, 95% CI: - 0.511 to - 0.251, p < 0.001). There was no effect of Necessity (ß = 0.006, 95% CI: - 0.145 to 0.158, p = 0.933) or Concerns (ß = 0.041, 95% CI: - 0.117 to 0.199, p = 0.614) on adherence. Necessity-concerns beliefs were also not significant mediators in the relationship between socio-clinico factors and medication adherence. CONCLUSIONS: Older age and lower barriers to adherence were associated with higher adherence scores. Necessity-concerns beliefs did not have a significant effect on adherence as majority of the patients identified forgetfulness as a reason for non-adherence.

COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries.

OBJECTIVE: Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. METHODS: A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization. RESULTS: We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%). CONCLUSION: Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.

Comparison of laboratory threshold criteria in drug-induced liver injury detection algorithms for use in pharmacovigilance.

PURPOSE: For the purpose of pharmacovigilance, we sought to determine the best performing laboratory threshold criteria to detect drug-induced liver injury (DILI) in the electronic medical records (EMR). METHODS: We compared three commonly used liver chemistry criteria from the DILI expert working group (DEWG), DILI network (DILIN), and Council for International Organizations of Medical Sciences (CIOMS), based on hospital EMR for years 2010 and 2011 (42 176 admissions), using independent medical record review. The performance characteristics were compared in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value, accuracy, F-measure, and area under the receiver operating characteristic curve (AUROC). RESULTS: DEWG had the highest PPV (5.5%, 95% CI: 4.1%-7.2%), specificity (97.0%, 95% CI: 96.8%-97.2%), accuracy (96.8%, 95% CI: 96.6%-97.0%) and F-measure (0.099). CIOMS had the highest sensitivity (74.0%, 95% CI: 64.3%-82.3%) and AUROC (85.2%, 95% CI: 80.8%-89.7%). Besides the laboratory criteria, including additional keywords in the classification algorithm improved the PPV and F-measure to a maximum of 29.0% (95% CI: 22.3%-36.5%) and 0.379, respectively. CONCLUSIONS: More stringent criteria (DEWG and DILIN) performed better in terms of PPV, specificity, accuracy and F-measure. CIOMS performed better in terms of sensitivity. An algorithm with high sensitivity is useful in pharmacovigilance for detecting rare events and to avoid missing cases. Requiring at least two abnormal liver chemistries during hospitalization and text-word searching in the discharge summaries decreased false positives without loss in sensitivity.

Improving medication adherence with adjuvant aromatase inhibitor in women with breast cancer: study protocol of a randomised controlled trial to evaluate the effect of short message service (SMS) reminder.

BACKGROUND: Medication adherence refers to whether a patient takes medication according to the frequency prescribed, or continues to take a prescribed medication. Inadequate adherence to medication may cause alterations in risk-benefit ratios, resulting in reduced benefits, increased risks or both, and is significantly associated with adverse clinical outcomes and higher healthcare costs. We aim to examine the effect of a computer generated short message service (SMS) reminder in improving medication adherence, and inhibiting the aromatisation process amongst breast cancer women receiving oral aromatase inhibitor therapy. METHODS/DESIGN: In this randomised controlled trial, eligible patients will be equally allocated to receive either SMS reminder or standard care. The former receives weekly SMS reminder to take medication while the latter does not receive any. The primary endpoint of medication adherence at 1-year is assessed using the Simplified Medication Adherence Questionnaire, and compared using the χ2 test. Adjustment for baseline covariate and potential confounders will be made using the logistic regression. Secondary outcomes involving estrone and androstenedione levels will be compared using the analysis of covariance, whereas the estradiol levels (< 18.4 pmol/L versus ≥18.4 pmol/L) will be compared using the χ2 test, and the logistic regression. Further, the assessment of knowledge, attitude, behaviour, and barriers and facilitating factors of medication adherence will be made via logistic regression. DISCUSSION: This will be the first study to evaluate short-term clinical outcomes from SMS reminder for breast cancer patients on aromatase inhibitor therapy. Random allocation to SMS reminder or control arm ensures that patients in both arms will be comparable with respect to demographic and clinical characteristics, and any difference in outcomes can be attributed to the intervention. Participants are not blinded to the assignment of intervention, thus there may be potential for bias in outcome assessments. TRIAL REGISTRATION: NCT02524548 . Retrospectively registered on 17 August 2015.

Systematic review and meta-analysis of algorithms used to identify drug-induced liver injury (DILI) in health record databases.

BACKGROUND & AIMS: Drug induced liver injury (DILI) is largely underreported, leading to underestimation of its burden. Electronic detection of DILI in healthcare databases shows promise to overcome the issues of spontaneous reporting. The performance of detection algorithms may vary because of inconsistent DILI definition and detection criteria. We performed a systematic review and meta-analysis to identify the DILI detection criteria used in health record databases and determine the performance characteristics of the detection algorithms. METHODS: We searched PubMed, EMBASE and Scopus for studies that utilized laboratory threshold criteria to identify DILI cases. Validation studies were included in the meta-analysis. Data were abstracted using standardized forms and quality was assessed using modified Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) criteria. We evaluate the performance characteristics of the detection algorithm by obtaining the pooled estimate of the positive predictive value (PPV) assuming a random effects model. RESULTS: A total of 29 studies met the inclusion criteria for the systematic review; 25 of these studies (n = 35 948) had PPV estimates for performing the meta-analysis. The PPV of DILI detection algorithms was low, ranging from 1.0% to 40.2%, with a pooled estimate of 14.6% (95% CI 10.7-18.9). Algorithms that performed better had prespecified exclusion diagnoses as well as drugs of interest to minimize false positives. CONCLUSION: Algorithm performance varied with different case definitions of DILI attributed to different laboratory threshold criteria, diagnosis codes, and study drugs.

Trends in incidence, prevalence, and survival of breast cancer in the United Kingdom from 2000 to 2021.

Breast cancer is the most frequently diagnosed cancer in females globally. However, we know relatively little about trends in males. This study describes United Kingdom (UK) secular trends in breast cancer from 2000 to 2021 for both sexes. We describe a population-based cohort study using UK primary care Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases. There were 5,848,436 eligible females and 5,539,681 males aged 18+ years, with ≥ one year of prior data availability in the study period. We estimated crude breast cancer incidence rates (IR), prevalence and survival probability at one-, five- and 10-years after diagnosis using the Kaplan-Meier method. Analyses were further stratified by age. Crude IR of breast cancer from 2000 to 2021 was 194.4 per 100,000 person-years for females and 1.16 for males. Crude prevalence in 2021 was 2.1% for females and 0.009% for males. Both sexes have seen around a 2.5-fold increase in prevalence across time. Incidence increased with age for both sexes, peaking in females aged 60-69 years and males 90+ . There was a drop in incidence for females aged 70-79 years. From 2003-2019, incidence increased > twofold in younger females (aged 18-29: IR 2.12 in 2003 vs. 4.58 in 2018); decreased in females aged 50-69 years; and further declined from 2015 onwards in females aged 70-89 years. Survival probability for females after one-, five-, and ten-years after diagnosis was 95.1%, 80.2%, and 68.4%, and for males 92.9%, 69.0%, and 51.3%. Survival probability at one-year increased by 2.08% points, and survival at five years increased by 5.39% from 2000-2004 to 2015-2019 for females, particularly those aged 50-70 years. For males, there were no clear time-trends for short-term and long-term survival probability. Changes in incidence of breast cancer in females largely reflect the success of screening programmes, as rates rise and fall in synchronicity with ages of eligibility for such programmes. Overall survival from breast cancer for females has improved from 2000 to 2021, again reflecting the success of screening programmes, early diagnosis, and improvements in treatments. Male breast cancer patients have worse survival outcomes compared to females, highlighting the need to develop male-specific diagnosis and treatment strategies to improve long-term survival in line with females.

Evaluating the comparability of osteoporosis treatments using propensity score and negative control outcome methods in UK and Denmark electronic health record databases.

Evidence on the comparative effectiveness of osteoporosis treatments is heterogeneous. This may be attributed to different populations and clinical practice, but also to differing methodologies ensuring comparability of treatment groups before treatment effect estimation and the amount of residual confounding by indication. This study assessed the comparability of denosumab vs oral bisphosphonate (OBP) groups using propensity score (PS) methods and negative control outcome (NCO) analysis. A total of 280 288 women aged ≥50 yr initiating denosumab or OBP in 2011-2018 were included from the UK Clinical Practice Research Datalink (CPRD) and the Danish National Registries (DNR). Balance of observed covariates was assessed using absolute standardized mean difference (ASMD) before and after PS weighting, matching, and stratification, with ASMD >0.1 indicating imbalance. Residual confounding was assessed using NCOs with ≥100 events. Hazard ratio (HR) and 95%CI between treatment and NCO were estimated using Cox models. Presence of residual confounding was evaluated with 2 approaches (1) >5% of NCOs with 95% CI excluding 1, (2) >5% of NCOs with an upper CI <0.75 or lower CI >1.3. The number of imbalanced covariates before adjustment (CPRD 22/87; DNR 18/83) decreased, with 2%-11% imbalance remaining after weighting, matching, or stratification. Using approach 1, residual confounding was present for all PS methods in both databases (≥8% of NCOs), except for stratification in DNR (3.8%). Using approach 2, residual confounding was present in CPRD with PS matching (5.3%) and stratification (6.4%), but not with weighting (4.3%). Within DNR, no NCOs had HR estimates with upper or lower CI limits beyond the specified bounds indicating residual confounding for any PS method. Achievement of covariate balance and determination of residual bias were dependent upon several factors including the population under study, PS method, prevalence of NCO, and the threshold indicating residual confounding.

Treatment groups in clinical practice may not be comparable as patient characteristics differ according to the need for the prescribed medication, known as confounding. We assessed comparability of 2 common osteoporosis treatments, denosumab and oral bisphosphonate, in 280 288 postmenopausal women using electronic health records from UK Clinical Practice Research Datalink (CPRD) and Danish National Registries (DNR). We evaluated comparability of recorded patient characteristics with 3 propensity score (PS) methods, matching, stratification, and weighting. We assessed residual confounding from unrecorded patient characteristics via negative control outcomes (NCOs), events known not to be associated with treatment such as delirium. We found that achieving comparability of osteoporosis treatment groups depended on the study population, PS method, and definition of residual confounding. Weighting and stratification performed the best in DNR and CPRD, respectively. Using a stricter threshold based on statistical significance for the NCO suggested that the treatment groups were not comparable, except for PS stratification in DNR. Applying clinically significant thresholds of treatment effect size showed comparability using weighting in CPRD and all PS methods in DNR. Studies should consider more than one PS method to test robustness and identify the largest number of NCO to give the greatest flexibility in detecting residual confounding.

Incidence, prevalence, and survival of lung cancer in the United Kingdom from 2000-2021: a population-based cohort study.

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.

Incidence, Prevalence, and Survival of Prostate Cancer in the UK.

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.

The Impact of the COVID-19 Pandemic on Incidence and Short-Term Survival for Common Solid Tumours in the United Kingdom: A Cohort Analysis.

Purpose: The COVID-19 pandemic profoundly affected healthcare systems and patients. There is a need to comprehend the collateral effects of the pandemic on non-communicable diseases. We examined the impact of the pandemic on short-term survival for common solid tumours, including breast, colorectal, head and neck, liver, lung, oesophageal, pancreatic, prostate, and stomach cancer in the UK. Methods: This was a population-based cohort study of electronic health records from the UK primary care Clinical Practice Research Datalink GOLD database. In sum, 12,259,744 eligible patients aged ≥18 years with ≥1 year's history identified from January 2000 to December 2022 were included. We estimated age-standardised incidence and short-term (one- and two-year) survival for several common cancers from 2000 to 2019 (in five-year strata) and compared these to 2020-2022 using the Kaplan-Meier method. Results: Incidence decreased for most cancers in 2020 and recovered to different extents in 2021-2022. Short-term survival improved for most cancers between 2000 and 2019, but then declined, albeit minimally, for those diagnosed in 2020-2022. This was most pronounced for colorectal cancer, with one-year survival falling from 78.8% (95% CI 78%-79.6%) in 2015-2019 to 77% (95% CI 75.6-78.3%) for those diagnosed in 2020-2022. Conclusion: Short-term survival for many cancers was impacted, albeit minimally, by the pandemic in the UK, with reductions in survivorship from colorectal cancer equivalent to returning to the mortality seen in the first decade of the 2000s. While data on longer-term survival are needed to fully comprehend the impact of COVID-19 on cancer care, our findings illustrate the need for an urgent and substantial commitment from the UK National Health Service to address the existing backlog in cancer screening and diagnostic procedures to improve cancer care and mortality.

Treatment of systemic lupus erythematosus: Analysis of treatment patterns in adult and paediatric patients across four European countries.

OBJECTIVE: Multiple treatment options are recommended for Systemic Lupus Erythematosus (SLE) by clinical guidelines. This study aimed to explore SLE treatment patterns as there is limited real-world data of SLE medication utilisation, especially in childhood-onset SLE (cSLE). METHODS: We conducted a longitudinal cohort study using five routinely collected healthcare databases from four European countries (United Kingdom, France, Germany, and Spain). We described the characteristics of adult and paediatric patients at time of SLE diagnosis. We calculated the percentage of patients commencing SLE treatments in the first month and year after diagnosis, reported number of prescriptions, starting dose, cumulative dose, and duration of each treatment, and characterised the line of therapy. RESULTS: We characterised 11,255 patients with a first diagnosis of SLE and included 5718 in our medication utilisation analyses. The majority of adult SLE patients were female (range 80-88 %), with median age of 49 to 54 years at diagnosis. In the paediatric cohort (n = 378), 66-83 % of SLE patients were female, with median age of 12 to 16 years at diagnosis. Hydroxychloroquine and glucocorticoids were common first-line treatments in both adults and children, with second-line treatments including mycophenolate mofetil and methotrexate. Few cases of monoclonal antibody use were seen in either cohort. Initial glucocorticoid dosing in paediatric patients was often higher than in adults. CONCLUSION: Treatment choices for adult SLE patients across four European countries were in line with recent therapeutic consensus guidelines. High glucocorticoid prescriptions in paediatric patients suggests the need for steroid-sparing treatment alternatives and paediatric specific guidelines.

Beliefs about medicines and adherence in women with breast cancer on adjuvant endocrine therapy.

The Beliefs about Medicines Questionnaire (BMQ) and Adherence Starts with Knowledge (ASK-12) questionnaire were originally developed and validated in Western populations to assess beliefs and barriers to medication adherence. The study aim is to validate the BMQ and ASK-12 questionnaire for use in a Singapore population with early stage breast cancer. English-speaking women on adjuvant endocrine therapy (n = 157) were recruited. The BMQ-Specific showed good internal consistency with structural validity. The internal consistency of BMQ-General and ASK-12 Behaviour scale improved with the new factor structure obtained from exploratory factor analysis. Further studies are needed to confirm these factor structures.

Unraveling COVID-19: A Large-Scale Characterization of 4.5 Million COVID-19 Cases Using CHARYBDIS.

Purpose: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD. Patients and Methods: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services. Results: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed. Conclusion: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.

How well does the MESTT correlate with CTCAE scale for the grading of dermatological toxicities associated with oral tyrosine kinase inhibitors?

BACKGROUND: Dermatological toxicities associated with tyrosine kinase inhibitors (TKIs) are commonly graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). A new tool has been proposed by the Multinational Association for Supportive Care in Cancer (MASCC), namely the MASCC EGFRI Skin Toxicity Tool (MESTT), as a class-specific grading system. This study was designed to assess the correlation between the severity grading of the dermatological toxicities associated with TKIs using the NCI-CTCAE v4.0 and the MESTT. PATIENT AND METHODS: One hundred patients were interviewed at the National Cancer Centre Singapore with the criteria of being on erlotinib, gefitinib, lapatinib, sorafenib, or sunitinib over 2 weeks and manifested dermatological toxicities. Dermatological toxicities were graded using CTCAE and MESTT 1, respectively, by a single observer. Spearman's correlation test was performed on the results. RESULTS: Sixty-five patients (65%) experienced papulopustular rash, 72 patients (72%) had pruritus, 85 patients (85%) had xerosis, 33 patients (33%) experienced nail changes, and 24 patients (24%) had alopecia. There was significant positive correlation between the two grading systems for all investigated dermatological toxicities, namely rash (r = 0.734), pruritus (r = 0.917), xerosis (r = 0.635), and paronychia (r = 0.611) at 99% confidence level. CONCLUSION: Good correlation was observed between the scales, but there is a tendency for the MESTT tended to report higher toxicity grades for rash, xerosis, and paronychia. The MESTT was also found to be more useful to grade rash specific to TKIs and had similar usefulness for grading other studied toxicities.