In pharmacoepidemiological analysis, one covariate that might act as a confounder is the type of prescriber issuing a prescription. The type of prescriber typically fulfills the criteria for confounding, as it is associated both with the exposure (e.g., prescriber types may differ in their choice of first-line treatment) and with the outcome (as different types of prescribers often treat patients with different disease severity). Additionally, the type of prescriber may correlate with other factors such as treatment adherence, surveillance, or coding practices. While information on the type of prescriber is often available to researchers, it is rarely employed to control for confounding in pharmacoepidemiological analyses. In an applied example, we conducted a cohort study using Danish healthcare registers from 2011 to 2018 to assess the risk of ischemic stroke associated with the use of direct oral anticoagulants (DOACs) compared to warfarin. We found a hazard ratio (HR) of 0.95 (95% CI: 0.90-1.01) for DOACs versus warfarin when adjusting only for age and sex. Further adjustment for prescriber type showed an effect of similar magnitude (HR 0.93; 95% CI: 0.87-0.98). However, in stratified analyses, we observed higher estimates in the group of general practitioners (HR 1.06; 95% CI: 0.94-1.2) compared to hospital prescribers (HR 0.88; 95% CI: 0.82-0.95), indicating potential effect modification. This highlights the potential value of prescriber type as an important covariate in pharmacoepidemiological analyses. Further research is needed to fully establish the importance of prescriber type in such analyses.

The use of tramadol and other opioids for pain management has been accompanied by a multitude of challenges and concerns worldwide. The use of tramadol saw a decline in Denmark during 2017-2019 accompanied by a slight increase in the use of morphine and oxycodone. Using the Danish National Prescription Registry and utilizing data until and including 2023, we aimed to provide updated data on the utilization patterns of tramadol and other opioids in Denmark. We found a 35% decline in the use of tramadol from 2017-2023 most likely due to media attention, regulatory actions, health campaigns, and targeted education of physicians and patients by the Danish health authorities. This decline was accompanied by an increase in the number of new (+90%) and current users of morphine (+57%) which surpassed those of tramadol, oxycodone, and other opioids in 2023.

Background: Oral corticosteroid use in asthma management can lead to serious adverse effects, but knowledge on usage trends are limited. We aimed to investigate this in a nationwide asthma cohort in Denmark from 1999-2018. Methods: By use of Danish nationwide registers, we identified all young adults (18-45 years) with two or more asthma drug collections within 12 months since the age of 15 as indicative of active asthma. Oral corticosteroid use was stratified by exposure level as high use (≥5 mg prednisolone/day) and low use (<5 mg/day) per year, age groups and gender. Lorenz curves were used to express the skewness of consumption among users. Results: We identified 318,950 unique individuals with active asthma during the study period with a median age of 29 years (interquartile range [IQR] 20-38 years) whereof 57% were women. The 1-year prevalence of oral corticosteroid users was stable at 4.8% (median, IQR 4.7%-4.8%), but with a nearly 40% decrease in high-users from 0.54% in 1999 to 0.33% in 2018. The median annual dose decreased from 500 mg/y in 1999 to 250 mg/y in 2018. We found a substantial skewness in the distribution of oral corticosteroid usage with 10% of users accounting for almost 50% of all oral corticosteroid use. Conclusions: Although the prevalence of oral corticosteroid users among young adults with active asthma in Denmark has been relatively stable from 1999-2018, we observed a decreasing trend in the prevalence of high-users and annual consumption.

Abstract Concomitant use of Vitamin K antagonists (VKA) and statins is frequent in cardiovascular patients. However, clinical guidelines on this drug combination are divergent. Therefore, we performed a systematic review according to the PRISMA guidelines to evaluate the effect of statin initiation on coagulation among VKA users. Applying two broad search strategies for the drug interaction between VKA and statins in both Embase and Pubmed, 8,623 unique hits were obtained. In the final sample eight studies were included. The most frequent used VKA in the studies was warfarin while simvastatin was the most commonly initiated statin. All included studies showed a minor increase in the anticoagulant effect of VKA following statin initiation during VKA treatment. The reported increases in mean INR ranged from 0.15-0.65. The effect is likely to be of limited clinical relevance but should be evaluated individually.

Initiation of statin treatment is suggested to increase the international normalised ratio (INR) among warfarin users. However, available data is limited and conflicting. We conducted a register-based cohort study to evaluate the drug-drug interaction between warfarin and statins. By linking data on INR measurements and filled prescriptions, we identified warfarin users 2000-2015 initiating simvastatin (n=1,363), atorvastatin (n=165), or rosuvastatin (n=23). Simvastatin initiation led to an increase in mean INR from 2.40 to 2.71, with INRs peaking after 4 weeks, corresponding to a mean change of 0.32 (95%CI 0.25-0.38). High-dose and low-dose simvastatin led to comparable changes (mean change 0.33 vs 0.29). Initiation of atorvastatin and rosuvastatin lead to INR increases of 0.27 (95%CI 0.12-0.42) and 0.30 (95%CI -0.09-0.69). In conclusion, initiation of simvastatin, atorvastatin, or rosuvastatin among warfarin users led to a minor increase in INR. The magnitude of this change is for most patients likely of limited clinical relevance.