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Background: Despite its potential value in register-based pharmacoepidemiologic research, recorded information on "indication for use" (INDO) in the Danish National Prescription Registry has rarely been used, likely because of questions about the variable's validity, which to our knowledge no study has systematically assessed. Methods: We extracted data on 80,814 prescriptions from the software systems (PharmaNet and C2) of five Danish community pharmacies filled between 4 and 16 February 2019 and 2020. Using the indication information recorded in the pharmacy software systems as the gold standard, we evaluated the extent and quality of the corresponding information from the Prescription Registry. Results: Of all prescriptions identified, we captured >99% in the Prescription Registry. The proportion of prescriptions with recorded indication codes in the Prescription Registry was 82% (n = 66,164) but was lower for C2 than PharmaNet. Correcting for the overrepresentation of C2 data in our sample, the estimated proportion of registration was ≈88%. Almost 100% (66,158 of 66,164) of the prescriptions with recorded indication codes in the Prescription Registry had correctly recorded indication codes. Nonspecific indication codes were present in 5.6%–36% of selected drugs and drug classes. Conclusions: Prescriptions filled at Danish community pharmacies are accurately captured by the Danish National Prescription Registry, and the recorded information on indication is generally valid and usable in research. However, minor concerns remain about missingness, nonspecific recorded indication codes, and lower validity, and a higher proportion of missingness of recorded indication codes is expected before 2017. A supplementary digital video by the article's co-author, Hanin Harbi, is available at http://links.lww.com/EDE/C89 [ABSTRACT FROM AUTHOR]

Background: Use of angiotensin-converting enzyme inhibitors (ACEIs)was associated with increased risk of lung cancer in a cohort study from the United Kingdom. We aimed to replicate these findings in a Danish population.Methods: We conducted a nested case-control study using data from 4 Danish national health and administrative registries. New users of ACEIs or angiotensin II receptor blockers in Denmark from January 1, 2000 were followed until December 31, 2015, incident lung cancer, death, or emigration. Each lung cancer case was matched with up to 20 controls on age, sex, duration of follow-up, and year of cohort entry using risk-set sampling. Conditional logistic regression was used to estimate odds ratios (ORs) for incident, histologically verified lung cancer with high use of ACEIs defined as a cumulative dose above 3650 defined daily doses. We examined different cumulative doses of ACEI (≤1800, 1801-3650, >3650 defined daily doses), examined whether the association varied with lung cancer histology, and repeated the analyses using thiazides as active comparator.Results: We included 9652 lung cancer cases matched to 190 055 controls. High use of ACEIs was associated with lung cancer (adjusted OR, 1.33 [95% CI, 1.08-1.62]). Lower cumulative doses showed neutral associations (≤1800 defined daily doses OR, 1.01 [95% CI, 0.94-1.09]; 1801-3650 defined daily doses OR, 1.03 [95% CI, 0.90-1.19]). CIs were wide and included the null when stratifying on histology. Using thiazides as active comparator yielded comparable results (OR, 1.34 [95% CI, 0.96-1.88]).Conclusions: Use of high cumulative ACEI doses was associated with modestly increased odds of lung cancer although use of lower doses showed neutral associations. The established benefits of ACEIs should be considered when interpreting these findings. [ABSTRACT FROM AUTHOR]

Background: We examined whether the apparent association between renal cell carcinoma (RCC) and use of dihydropyridine calcium channel blockers (CCBs) was explained by confounding by indication since hypertension, the main indication for CCBs, is a risk factor for RCC.Methods: Using Danish health registries, we conducted a nested case-control study including 7315 RCC cases during 2000-2015. We matched each case with up to 20 controls on age and sex using risk-set sampling. We estimated odds ratios (ORs) for long-term CCB use associated with RCC using conditional logistic regression. We addressed confounding by indication by (1) adjusting for hypertension severity indicators; (2) evaluating dose-response patterns; (3) examining whether other first-line anti-hypertensives were associated with RCC; and (4) using an active comparator new user design by nesting the study in new users of CCBs or angiotensin-converting enzyme inhibitors (ACEIs).Results: The adjusted OR for RCC associated with long-term CCB use compared to non-use was 1.76 (1.63-1.90). After we additionally adjusted for hypertension severity indicators, the OR remained elevated (OR 1.37; confidence interval [CI] 1.25, 1.49) with evidence of a dose-response pattern. Other anti-hypertensives were also associated with RCC, for example, ACEIs (OR 1.27; 95% CI = 1.16, 1.39) and thiazides (OR 1.22; 95% CI = 1.12, 1.34). In the active comparator new user design, the OR was 1.21 (95% CI = 0.95, 1.53) for use of CCBs compared with ACEIs.Conclusions: In this population, confounding by indication appeared to explain at least part of the association between RCC and dihydropyridine CCBs. [ABSTRACT FROM AUTHOR]

Background: Procedure codes in the Danish National Patient Registry are used for administrative purposes and are a potentially valuable resource for epidemiologic research. To our knowledge, the validity of antineoplastic procedure codes has only been evaluated in one study.Methods: We randomly extracted a sample of 420 patients in the Southern Region of Denmark with a diagnosis of colorectal cancer and an oncology contact during 2016-2018. Using the medical record as gold standard, we computed the positive predictive value (PPV) and sensitivity of antineoplastic procedure codes recorded in the Danish National Patient Registry.Results: We identified 2,243 codes for antineoplastic treatments in the registry and 2,299 in the medical records. We confirmed that 213 of 214 patients with registered therapies in the Danish National Patient Registry received therapy, corresponding to a PPV of "any registration" of 1.00 (95% confidence interval [CI] = 0.97, 1.00). Considering single registrations, the overall PPV was 0.95 (95% CI = 0.94, 0.95), and the overall sensitivity was 0.90 (95% CI = 0.89, 0.91). Number of recorded treatments and treatments administered were strongly correlated. Considering the most frequent single antineoplastic regimens, PPV ranged from 0.90 (95% CI = 0.87, 0.92) for capecitabine to 0.98 (95% CI = 0.95, 1.00) for cetuximab, whereas sensitivity ranged from 0.81 (95% CI = 0.75, 0.87) for 5-fluorouracil and irinotecan (FOLFIRI) regimen to 0.97 (95% CI = 0.94, 0.99) for bevacizumab. Analysis per hospital showed the highest validity of registrations at the University Hospital.Conclusion: The validity of antineoplastic procedure codes in the Danish National Patient Registry is generally high and thus usable for epidemiologic research. [ABSTRACT FROM AUTHOR]

Background: There have been concerns that the antifibrinolytic drug tranexamic acid (TXA) might increase the postoperative risk of cardiovascular events. Our objective was to determine whether perioperative TXA use is associated with cardiovascular events and death within 30 days after primary total hip arthroplasty (THA).Methods: We conducted a nationwide cohort study of cardiovascular outcomes after perioperative exposure to tranexamic acid during THA. We included 45,290 patients who had a THA in the study period of 2006 to 2013; 38,586 received perioperative TXA, and 6,704 did not. Propensity scores were calculated on the basis of age, sex, income, year of surgery, Elixhauser comorbidity index, and a variety of comorbidities and coprescribed medications. The primary outcome was venous thromboembolism. The secondary outcomes were deep venous thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, and all-cause mortality. Data were analyzed using Cox regression, either in a multivariable model with inclusion of covariates (full cohorts) or in propensity-score-matched cohorts.Results: After propensity score matching, all prognostic covariates balanced well. In the matched cohort, TXA use was not found to significantly increase the risk of venous thromboembolism (hazard ratio [HR] = 1.18; 95% confidence interval [CI] = 0.83 to 1.68), deep vein thrombosis (HR = 1.15; CI = 0.78 to 1.68), pulmonary embolism (HR = 1.50; CI = 0.60 to 3.78), myocardial infarction (HR = 0.83; CI = 0.46 to 1.50), ischemic stroke (HR = 0.89; CI = 0.39 to 2.01), or all-cause mortality (HR = 0.73; CI = 0.41 to 1.28). Similar results were found in the multivariable Cox regression analyses.Conclusions: Our data do not support a detrimental effect of TXA on the risk of cardiovascular events or death following THA.Level Of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: The nationwide Danish Cancer Registry and the Danish Melanoma Database both record data on melanoma for purposes of monitoring, quality assurance, and research. However, the data quality of the Cancer Registry and the Melanoma Database has not been formally evaluated.Methods: We estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n = 200) and the Melanoma Database (n = 200) during 2004-2014, using the Danish Pathology Registry as "gold standard" reference. We further validated tumor characteristics in the Cancer Registry and the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in 2004-2014.Results: The PPVs of melanoma in the Cancer Registry and the Melanoma Database were 97% (95% CI = 94, 99) and 100%. The sensitivity was 90% in the Cancer Registry and 77% in the Melanoma Database. The PPV of in situ melanomas in the Melanoma Database was 97% and the sensitivity was 56%. In the Melanoma Database, we observed PPVs of ulceration of 75% and Breslow thickness of 96%. The PPV of histologic subtypes varied between 87% and 100% in the Cancer Registry and 93% and 100% in the Melanoma Database. The PPVs for anatomical localization were 83%-95% in the Cancer Registry and 93%-100% in the Melanoma Database.Conclusions: The data quality in both the Cancer Registry and the Melanoma Database is high, supporting their use in epidemiologic studies. [ABSTRACT FROM AUTHOR]

Background: Use of angiotensin-converting enzyme inhibitors (ACEIs)was associated with increased risk of lung cancer in a cohort study from the United Kingdom. We aimed to replicate these findings in a Danish population., Methods: We conducted a nested case-control study using data from 4 Danish national health and administrative registries. New users of ACEIs or angiotensin II receptor blockers in Denmark from January 1, 2000 were followed until December 31, 2015, incident lung cancer, death, or emigration. Each lung cancer case was matched with up to 20 controls on age, sex, duration of follow-up, and year of cohort entry using risk-set sampling. Conditional logistic regression was used to estimate odds ratios (ORs) for incident, histologically verified lung cancer with high use of ACEIs defined as a cumulative dose above 3650 defined daily doses. We examined different cumulative doses of ACEI (≤1800, 1801-3650, >3650 defined daily doses), examined whether the association varied with lung cancer histology, and repeated the analyses using thiazides as active comparator., Results: We included 9652 lung cancer cases matched to 190 055 controls. High use of ACEIs was associated with lung cancer (adjusted OR, 1.33 [95% CI, 1.08-1.62]). Lower cumulative doses showed neutral associations (≤1800 defined daily doses OR, 1.01 [95% CI, 0.94-1.09]; 1801-3650 defined daily doses OR, 1.03 [95% CI, 0.90-1.19]). CIs were wide and included the null when stratifying on histology. Using thiazides as active comparator yielded comparable results (OR, 1.34 [95% CI, 0.96-1.88])., Conclusions: Use of high cumulative ACEI doses was associated with modestly increased odds of lung cancer although use of lower doses showed neutral associations. The established benefits of ACEIs should be considered when interpreting these findings.