Background: For a patient cohort, access to linkable population-based registries permits sampling of a comparison cohort from the general population, thereby contributing to the understanding of the disease in a population context. However, sampling without replacement in random order can lead to immortal time bias by conditioning on the future. Aim: We compared the following strategies for sampling comparison cohorts in matched cohort studies with respect to time to ischemic stroke and mortality: sampling without replacement in random order; sampling with replacement; and sampling without replacement in chronological order. Methods: We constructed index cohorts of individuals from the Danish general population with no particular trait, except being alive and without ischemic stroke on the index date. We also constructed index cohorts of persons aged >50 years from the general population. We then applied the sampling strategies to sample comparison cohorts (5:1 or 1:1) from the Danish general population and compared outcome risks between the index and comparison cohorts. Finally, we sampled comparison cohorts for a heart failure cohort using each strategy. Results: We observed increased outcome risks in comparison cohorts sampled 5:1 without replacement in random order compared to the index cohorts. However, these increases were minuscule unless index persons were aged >50 years. In this setting, sampling without replacement in chronological order failed to sample a sufficient number of comparators, and the mortality risks in these comparison cohorts were lower than in the index cohorts. Sampling 1:1 showed no systematic difference between comparison and index cohorts. When we sampled comparison cohorts for the heart failure patients, we observed a pattern similar to when index persons were aged >50 years. Conclusion: When index persons were aged >50 years, ie, had high outcome risks, sampling 5:1 without replacement introduced bias. Sampling with replacement or 1:1 did not introduce bias.

BACKGROUND: Osteonecrosis of the jaw (ONJ) is an adverse effect of antiresorptive treatment. This study estimated incidence proportions and incidence rates of ONJ in cancer patients with bone metastases from solid tumors treated for the prevention of skeletal‐related events in routine clinical practice.METHODS: This cohort study in Denmark, Norway, and Sweden in 2011‐2018 included 3 treatment cohorts: a denosumab inception cohort (DEIC), a zoledronic acid inception cohort (ZAIC), and a denosumab‐switch cohort (DESC). The authors estimated 1‐ to 5‐year incidence proportions and incidence rates of ONJ overall, by cancer site (breast, prostate, or other solid tumor), and by country. ONJ diagnoses were confirmed by adjudication.RESULTS: There were 1340 patients in the DEIC, 1352 in the ZAIC, and 408 in the DESC. The median ages of the 3 cohorts were 70, 69, and 70 years, respectively; the proportions of men were 72.6%, 53.8%, and 48.3%, respectively; and the median follow‐up was 19.8, 12.9, and 13.3 months, respectively. The 5‐year incidence proportions of ONJ were 5.7% (95% confidence interval [CI], 4.4%‐7.3%) in the DEIC, 1.4% (95% CI, 0.8%‐2.3%) in the ZAIC, and 6.6% (95% CI, 4.2%‐10.0%) in the DESC. The corresponding ONJ incidence rates per 100 person‐years were 3.0 (95% CI, 2.3‐3.7), 1.0 (95% CI, 0.6‐1.5), and 4.3 (95% CI, 2.8‐6.3). Incidence proportions and incidence rates were highest in patients with prostate cancer and in Denmark.CONCLUSIONS: This study provides estimates of the risk of medically confirmed ONJ among patients initiating denosumab or zoledronic acid in routine clinical practice in 3 Scandinavian countries. The results varied by cancer site and by country.LAY SUMMARY: Denosumab and zoledronic acid reduce the risk of bone fractures, pain, and surgery in patients with advanced cancers involving bone. Osteonecrosis of the jaw (ONJ)—death of a jawbone—is a known side effect of treatment with denosumab or zoledronic acid. The authors examined almost 2900 denosumab‐ or zoledronic acid–treated patients with cancer in Denmark, Norway, and Sweden. Over the course of 5 years, ONJ developed in 5.7% of the patients whose initial treatment was denosumab, in 1.4% of the patients whose initial treatment was zoledronic acid, and in 6.6% of the patients who switched from zoledronic acid to denosumab.

Purpose: Creatinine data are key in identifying acute and chronic kidney disease. In Denmark, routine clinical care creatinine data have been collected regionally in the Clinical Laboratory Information System Research Database (LABKA) since the 1990s and nationwide in the Register of Laboratory Results for Research (RLRR) since 2013. Here we describe the geographical coverage of the databases and characteristics of Danish individuals with creatinine tests. This information is pivotal for the design and interpretation of studies using these data to examine kidney disease epidemiology. Patients and Methods: We included all creatinine tests in LABKA and RLRR from 1990 through 2018. The daily number of creatinine tests by municipality and region of residence were plotted and geographical coverage was ascertained. In addition, we characterized a contemporary cohort of creatinine-tested individuals in 2016– 2018. Results: During 1990– 2018, 61,011,941 creatinine tests were available for 4,647,966 unique Danish residents. The North Denmark Region was the first region to achieve complete reporting in November 2004, and nationwide reporting was complete starting in October 2015. In each year from 2016 to 2018, more than a third of Danish residents had a recorded creatinine measurement, with the highest proportion of tested individuals aged 77– 87 years and the lowest proportion aged 3– 5 years. During 2016– 2018, the creatinine-tested cohort had a median age of 53 years (IQR, 35– 67 years) and included 54.3% women. The most common comorbidity was a hospital-based diagnosis of hypertension (12.0%), and the most common prescription drug was angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (15.8%). Conclusion: In combination, the population-based LABKA and RLRR databases provide regional creatinine data with long follow-up and nationwide data for the Danish population. There was considerable variation in the time of complete geographical coverage by region, which needs to be considered when using these data for studies on kidney disease epidemiology.

To examine the prevalence of lifestyle diagnosis codes recorded in the Danish National Registry of Patients (DNRP). We identified all hospital contacts in Denmark 1999–2012 with a diagnosis of overweight, obesity, physical inactivity, current tobacco smoking, and/or excessive alcohol consumption. We computed the annual prevalence per 1000 hospital contacts of these diagnoses overall and by baseline characteristics. Among 56,665,048 hospital contacts, the overall prevalence of recording per 1000 hospital contacts was 4.87 for a diagnosis of obesity, 2.36 for overweight, 2.90 for smoking, 0.39 for excessive alcohol consumption, and 0.47 for physical inactivity. Between 1999 and 2012, marked increases were noted for the prevalence of recorded obesity (30-fold, from 0.26 to 8.02), smoking (26-fold, from 0.18 to 4.88), and overweight (14-fold, from 0.23 to 3.52). Diagnosis coding of excessive alcohol consumption and physical inactivity remained at a very low level. The prevalence of recorded lifestyle risk factors varied substantially according to geographical regions, type of hospital contact, patient age, sex and underlying disease. In 2012, the prevalence of codes for obesity were highest among patients with diabetes (15.64 per 1000), COPD (12.95 per 1000), and congestive heart failure (11.24 per 1000). Codes for smoking were prevalent among patients with COPD (14.11 per 1000), liver disease (12.68 per 1000), and peripheral vascular disease (8.52 per 1000). Despite increasing prevalence of adverse lifestyle risk factors recorded in the DNRP, the much higher prevalence of similar lifestyle risk factors in health surveys suggests that the completeness of coding in the DNRP remains poor.

BACKGROUND: Empagliflozin and dapagliflozin have proven cardiovascular benefits in people with type 2 diabetes at high cardiovascular risk, but their comparative effectiveness is unknown. METHODS: This study used nationwide, population-based Danish health registries to emulate a hypothetical target trial comparing empagliflozin versus dapagliflozin initiation, in addition to standard care, among people with treated type 2 diabetes from 2014 through 2020. The outcome was a composite of myocardial infarction, ischemic stroke, heart failure (HF), or cardiovascular death (major adverse cardiovascular event). Participants were followed until an outcome, emigration, or death occurred; 6 years after initiation; or December 31, 2021, whichever occurred first. Logistic regression was used to compute inverse probability of treatment and censoring weights, controlling for 57 potential confounders. In intention-to-treat analyses, 6-year adjusted risks, risk differences, and risk ratios, considering noncardiovascular death competing events, were estimated. Analyses were stratified by coexisting atherosclerotic cardiovascular disease and HF. A per-protocol design was performed as a secondary analysis. RESULTS: There were 36 670 eligible empagliflozin and 20 606 eligible dapagliflozin initiators. In the intention-to-treat analysis, the adjusted 6-year absolute risk of major adverse cardiovascular event was not different between empagliflozin and dapagliflozin initiators (10.0% versus 10.0%; risk difference, 0.0% [95% CI, −0.9% to 1.0%]; risk ratio, 1.00 [95% CI, 0.91 to 1.11]). The findings were consistent in people with atherosclerotic cardiovascular disease (risk difference, −2.3% [95% CI, −8.2% to 3.5%]; risk ratio, 0.92 [95% CI, 0.74 to 1.14]) and without atherosclerotic cardiovascular disease (risk difference, 0.3% [95% CI, −0.6% to 1.2%]; risk ratio, 1.04 [95% CI, 0.93 to 1.16]) and in people with HF (risk difference, 1.1% [95% CI, −6.5% to 8.6%]; risk ratio, 1.04 [95% CI, 0.79 to 1.37]) and without HF (risk difference, −0.1% [95% CI, −1.0% to 0.8%]; risk ratio, 0.99 [95% CI, 0.90 to 1.09]). The 6-year risks of major adverse cardiovascular event were also not different in the per-protocol analysis (9.1% versus 8.8%; risk difference, 0.2% [95% CI, −2.1% to 2.5%]; risk ratio, 1.03 [95% CI, 0.80 to 1.32]). CONCLUSIONS: Empagliflozin and dapagliflozin initiators had no differences in 6-year cardiovascular outcomes in adults with treated type 2 diabetes with or without coexisting atherosclerotic cardiovascular disease or HF.

To assess if mammographic density (MD) changes during neoadjuvant breast cancer treatment and is predictive of a pathological complete response (pCR). We prospectively included 200 breast cancer patients assigned to neoadjuvant chemotherapy (NACT) in the NeoDense study (2014-2019). Raw data mammograms were used to assess MD with a fully automated volumetric method and radiologists categorized MD using the Breast Imaging-Reporting and Data System (BI-RADS), 5th Edition. Logistic regression was used to calculate odds ratios (OR) for pCR comparing BI-RADS categories c vs. a, b, and d as well as with a 0.5% change in percent dense volume adjusting for baseline characteristics. The overall median age was 53.1 years, and 48% of study participants were premenopausal pre-NACT. A total of 23% (N = 45) of the patients accomplished pCR following NACT. Patients with very dense breasts (BI-RADS d) were more likely to have a positive axillary lymph node status at diagnosis: 89% of the patients with very dense breasts compared to 72% in the entire cohort. A total of 74% of patients decreased their absolute dense volume during NACT. The likelihood of accomplishing pCR following NACT was independent of volumetric MD at diagnosis and change in volumetric MD during treatment. No trend was observed between decreasing density according to BI-RADS and the likelihood of accomplishing pCR following NACT. The majority of patients decreased their MD during NACT. We found no evidence of MD as a predictive marker of pCR in the neoadjuvant setting.