IntroductionVaccine safety surveillance commonly includes a serial testing approach with a sensitive method for ‘signal generation’ and specific method for ‘signal validation.’ The extent to which serial testing in real-world studies improves or hinders overall performance in terms of sensitivity and specificity remains unknown.MethodsWe assessed the overall performance of serial testing using three administrative claims and one electronic health record database. We compared type I and II errors before and after empirical calibration for historical comparator, self-controlled case series (SCCS), and the serial combination of those designs against six vaccine exposure groups with 93 negative control and 279 imputed positive control outcomes.ResultsThe historical comparator design mostly had fewer type II errors than SCCS. SCCS had fewer type I errors than the historical comparator. Before empirical calibration, the serial combination increased specificity and decreased sensitivity. Type II errors mostly exceeded 50%. After empirical calibration, type I errors returned to nominal; sensitivity was lowest when the methods were combined.ConclusionWhile serial combination produced fewer false-positive signals compared with the most specific method, it generated more false-negative signals compared with the most sensitive method. Using a historical comparator design followed by an SCCS analysis yielded decreased sensitivity in evaluating safety signals relative to a one-stage SCCS approach. While the current use of serial testing in vaccine surveillance may provide a practical paradigm for signal identification and triage, single epidemiological designs should be explored as valuable approaches to detecting signals.

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.PurposeTo characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns.MethodsWe 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 & GE; 18 years, with & GE; 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.ResultsOverall, 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.ConclusionOur results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare.

Here, the authors show that longer duration and greater degree of overweight and obesity during early adulthood as well as younger age of onset of a high body mass index are associated with a higher risk of 18 cancer types.
Single body mass index (BMI) measurements have been associated with increased risk of 13 cancers. Whether life course adiposity-related exposures are more relevant cancer risk factors than baseline BMI (ie, at start of follow-up for disease outcome) remains unclear. We conducted a cohort study from 2009 until 2018 with population-based electronic health records in Catalonia, Spain. We included 2,645,885 individuals aged & GE;40 years and free of cancer in 2009. After 9 years of follow-up, 225,396 participants were diagnosed with cancer. This study shows that longer duration, greater degree, and younger age of onset of overweight and obesity during early adulthood are positively associated with risk of 18 cancers, including leukemia, non-Hodgkin lymphoma, and among never-smokers, head and neck, and bladder cancers which are not yet considered as obesity-related cancers in the literature. Our findings support public health strategies for cancer prevention focussing on preventing and reducing early overweight and obesity.

The association between long-term exposure to ambient air pollutants and severe COVID-19 is uncertain. We followed 4,660,502 adults from the general population in 2020 in Catalonia, Spain. Cox proportional models were fit to evaluate the association between annual averages of PM(2.5), NO(2), BC, and O(3) at each participant’s residential address and severe COVID-19. Higher exposure to PM(2.5,) NO(2,) and BC was associated with an increased risk of COVID-19 hospitalization, ICU admission, death, and hospital length of stay. An increase of 3.2 µg/m(3) of PM(2.5) was associated with a 19% (95% CI, 16-21) increase in hospitalizations. An increase of 16.1 µg/m(3) of NO(2) was associated with a 42% (95% CI, 30-55) increase in ICU admissions. An increase of 0.7 µg/m(3) of BC was associated with a 6% (95% CI, 0-13) increase in deaths. O(3) was positively associated with severe outcomes when adjusted by NO(2). Our study contributes robust evidence that long-term exposure to air pollutants is associated with severe COVID-19.

OBJECTIVE: We aimed to estimate how longitudinal trends in cardiovascular disease, hypertension and type 2 diabetes mellitus incidence in Catalonia, Spain from 2009 to 2018 may differ by age, sex and socioeconomic deprivation. DESIGN: Cohort study using prospectively collected data. SETTING: Electronic health records from primary healthcare centres in Catalonia, Spain. PARTICIPANTS: 3 247 244 adults (=40 years). OUTCOME MEASURES: We calculated the annual incidence (per 1000 persons-year) and incidence rate ratios (IRR) between three time periods of cardiovascular disease, hypertension and type 2 diabetes mellitus to measure trends and changes in incidence during the study period. RESULTS: In 2016-2018 compared with 2009-2012, cardiovascular disease incidence increased in the 40-54 (eg, IRR=1.61, 95% CI: 1.52 to 1.69 in women) and 55-69 age groups. There was no change in cardiovascular disease incidence in women aged 70+ years, and a slight decrease in men aged 70+ years (0.93, 0.90 to 0.95). Hypertension incidence decreased in all age groups for both sexes. Type 2 diabetes mellitus incidence decreased in all age groups for both sexes (eg, 0.72, 0.70 to 0.73 in women aged 55-69 years), except for the 40-54 year age group (eg, 1.09, 1.06 to 1.13 in women). Higher incidence levels were found in the most deprived areas, especially in the 40-54 and 55-69 groups. CONCLUSIONS: Overall cardiovascular disease incidence has increased while hypertension and type 2 diabetes mellitus incidence have decreased in the last years in Catalonia, Spain, with differences in trends by age group and socioeconomic deprivation.