Maria Rikala

Validity of the Finnish Prescription Register for measuring psychotropic drug exposures among elderly finns: a population-based intervention study.

BackgroundPharmacoepidemiological studies assessing the associations between psychotropic drug use and adverse events in the elderly frequently employ automated pharmacy databases as the source of exposure data. However, information on the validity of these databases for estimating psychotropic drug exposures in elderly people is scarce.ObjectiveThis study evaluated the validity of the Finnish Prescription Register for estimating current exposures to psychotropic drugs in elderly people. Furthermore, the potential change in the validity over time was determined.MethodsThis was a population-based intervention study (GeMS; Geriatric Multidisciplinary Strategy for the Good Care of the Elderly) conducted between 2004 and 2007. Initially, 1000 randomly selected persons aged ≥75 years living in the City of Kuopio, Finland, in November 2003 were invited to participate in the study. Of these, 716 agreed to participate at baseline (2004) and 570 were still available for 3-year follow-up (2007). The validity of the Prescription Register was assessed by comparing it with the self-reported information collected by interviews in 2004 and in 2007 in the GeMS study. Using the self-reported data as a reference standard, sensitivity, specificity and Cohen’s κ statistic (measure of inter-rater agreement for qualitative [categorical] items) with 95% confidence intervals were computed for different categories and subcategories of psychotropic drugs, applying fixed-time windows of 4, 6 and 12 months.ResultsIn 2007, the sensitivity varied between psychotropic categories and subcategories, being generally highest with the 12-month time window (0.57–0.96). The specificity was highest with the 4-month time window (0.94–0.99), showing a slight tendency to decrease with an extended time window. The sensitivity and specificity were highest for antidepressants and antipsychotics, followed by benzodiazepines. The agreement was almost perfect (κ=0.81–1.00) or substantial (κ=0.61–0.80) for all categories and subcategories of psychotropic drugs. Few differences in validity were observed between the two years.ConclusionUsing self-reported data as a reference standard, the Prescription Register provides valid information on current exposures to antidepressants and antipsychotics in elderly people if the time window is selected with adequate consideration. However, the validity is lower for benzodiazepines, suggesting that other sources of information should be considered when performing pharmacoepidemiological studies.

Measurement of statin exposure in the absence of information on prescribed doses

Letter to the editor Pharmacoepidemiological studies on statin use and effectiveness frequently use pharmacy-claims databases as a source of drug exposure data. A variety of methods have been developed to estimate adherence and persistence based on pharmacy-claims databases [1–3]. In each method, theoretical duration of prescriptions is estimated by dividing the quantity dispensed by the prescribed dose. However, many pharmacyclaims databases, including all databases in the Nordic countries, do not include information on days’ supply or prescribed doses in a structured format [4]. Therefore, theoretical duration of statin prescriptions is often estimated based on assumed doses, such as one unit per day [5, 6] or a dose equal to defined daily dose (DDD) per day [7]. In this study, we evaluated the validity of the dosage assumptions of one unit per day and DDD per day for estimating the theoretical duration of statin prescriptions. We identified all statin prescriptions (Anatomical Therapeutic Chemical classification code C10AA [8]) dispensed in May 2007 from the Finnish Prescription Register. We converted free-text dosing instructions into numerical form and analyzed the proportions of prescriptions in which the prescribed daily dose deviated from one unit and DDD, using DDDs available in 2014 [8]. In addition, we described the distribution of prescribed daily doses of statins with means, standard deviations, medians and interquartile ranges. Of all statin prescriptions (n=153,664), 4.2 % were prescribed with a dose other than one unit per day (Table 1). The proportion varied from 0.7 to 12.9 % across individual statins. In contrast, 90.5% of statin prescriptions were prescribed with a dose other than DDD per day. Among individual statins, the proportion varied from 21.8 to 100 %, being 99.2 % for simvastatin. The proportion was similar (99.9 % of simvastatin prescriptions) if the former version of the DDD (15mg) was applied. Our study indicated that the duration of statin prescriptions can be validly estimated by assuming a daily dose of one unit. Our finding is in accordance with two previous studies showing that at least ∼95 % of statin prescriptions are prescribed with a daily dose of one unit [9, 10]. Furthermore, we showed that only one in ten statin prescriptions may be prescribed with a dose equal to DDD per day, indicating that assumed dose of DDD per day would most likely either overor underestimate the duration of statin prescriptions. This would lead to misclassifications of adherence and persistence levels and consequently biased measures of association when studying health outcomes associated with adherence to and discontinuation of statin therapy. Despite the fact that prescribed doses of statins have shown some differences between European countries [11] and seem to have increased over time [11–13], we believe that our finding about lack of validity of the dosage assumption of DDD per day is generalizable to other countries and time periods because statins are unlikely to be prescribed with a dose equal to DDD only. In addition, for statins other than atorvastatin and rosuvastatin, DDD is an average of two T. Romppainen : E. Aarnio School of Pharmacy, University of Eastern Finland, Kuopio, Finland

Channelling of Statin Use towards Low‐Risk Population and Patients with Diabetes

This study based on nationwide comprehensive health registers analysed trends in characteristics of statin users in the whole community‐dwelling population of Finland between 1999 and 2008. The annual number of incident users (defined as those purchasing statins for the first time ever) increased 1.6‐fold from 50,125 to 78,058 and that of ongoing users (including continuous users and re‐initiators) increased 4.6‐fold from 114,091 to 521,211. The proportion of incident users without cardiovascular disease (CVD) or diabetes increased from 23.6% to 27.8%, while the proportion of those with diabetes increased from 15.7% to 19.5%. An increasing proportion of ongoing users had diabetes (from 13.8% to 22.8%). The proportion of ongoing users without CVD or diabetes remained below one‐fifth; however, their number increased five‐fold. Over the study period, there was an obvious shift towards prescribing of higher statin doses both among incident and ongoing users. In conclusion, statin use is expanding to individuals with low cardiovascular risk despite the fact that clinical guidelines emphasize interventions other than pharmacotherapy for this population. At the same time, statin use is increasingly targeted to patients with diabetes, a high‐risk group that is likely to benefit from it.

Natural history of bleeding and characteristics of early bleeders among warfarin initiators – a cohort study in Finland

Aims The demand for oral anticoagulant therapy will continue to increase in the future along with the aging of the population. This study aimed to determine the rate of bleeding requiring hospitalization and to characterize early bleeders among persons initiating warfarin therapy. Characterization of those most susceptible to early bleeding is important in order to increase the safety of warfarin initiation. Patients and methods Using data from nationwide health registers, we identified persons initiating warfarin therapy between January 1, 2009 and June 30, 2012, n=101,588, and followed them until hospitalization for bleeding, death, or administrative end of the study (December 31, 2012). We defined early bleeders as persons with a bleeding requiring hospitalization within 30 days since warfarin initiation. Results The rate of hospitalization for bleeding during a median follow-up of 1.9 years was 2.6% per person-year (95% confidence interval [CI] 2.5%–2.7%), with a peak within the first 30 days of warfarin initiation (6.5% per person-year, 95% CI 6.0%–7.1%). In a multivariable Cox proportional hazards regression analysis, early bleeders were characterized by prior bleeding (<180 days before initiation, hazard ratio [HR] =13.7, 95% CI 10.9–17.1; during 180 days–7 years before initiation, HR =1.48, 95% CI 1.15–1.90), male sex (HR =1.32, 95% CI 1.10–1.57), older age (HR =1.13, 95% CI 1.04–1.22, per 10-year increase), venous thrombosis (HR =1.83, 95% CI 1.44–2.34), pulmonary embolism (HR =1.46, 95% CI 1.11–1.91), alcohol abuse (HR =1.59, 95% CI 1.08–2.35), rheumatic disease (HR =1.40, 95% CI 1.07–1.83), and exposure to drugs with dynamic interaction mechanism with warfarin (HR =1.43, 95% CI 1.20–1.71). In age-adjusted models, Charlson comorbidity index and number of drugs predicted a graded increase in the hazard of early bleeding. Conclusion The rate of hospitalizations for bleeding peaked in the beginning of warfarin therapy. Early bleeders were characterized by venous thrombosis, pulmonary embolism, and factors that increase bleeding risk without affecting the international normalized ratio.

Co-Prescribing of Potentially Interacting Drugs during Warfarin Therapy – A Population-Based Register Study

We analysed the occurrence of co‐prescribing of potentially interacting drugs during warfarin therapy in the community‐dwelling population of Finland. We identified drugs having interaction potential with warfarin using the Swedish Finnish INteraction X‐referencing drug–drug interaction database (SFINX) and obtained data on drug purchases from the nationwide Prescription Register. We defined warfarin users as persons purchasing warfarin in 2010 (n = 148,536) and followed them from their first prescription in 2010 until the end of the calendar year. Co‐prescribing was defined as at least 1‐day overlap between warfarin and interacting drug episodes. In addition, we identified persons who initiated warfarin therapy between 1 January 2007 and 30 September 2010 (n = 110,299) and followed these incident users for a 3‐month period since warfarin initiation. Overall, 74.4% of warfarin users were co‐prescribed interacting drugs. Co‐prescribing covered 46.4% of the total person‐years of warfarin exposure. Interacting drugs that should be avoided with warfarin were co‐prescribed for 13.4% of warfarin users. The majority of the co‐prescriptions were for drugs that are not contraindicated during warfarin therapy but require special consideration. Among incident users, 57.1% purchased potentially interacting drugs during the 3‐month period after initiation, while 9.0% purchased interacting drugs that should be avoided with warfarin. To conclude, the occurrence of co‐prescribing of potentially interacting drugs was high during warfarin therapy. Our findings highlight the importance of close monitoring of warfarin therapy and the need for further studies on the clinical consequences of co‐prescribing of interacting drugs with warfarin.

Measuring psychotropic drug exposures in register-based studies – validity of a dosage assumption of one unit per day in older Finns

Pharmacoepidemiological studies provide valuable information on the relationships between psychotropic drug use and adverse outcomes in older people. To minimize the influence of misclassification bias in pharmacoepidemiological studies, more emphasis should be given to methodological aspects of exposure assessment. This study evaluated the validity of a dosage assumption of one unit per day for measuring legend duration of psychotropic drug exposures among older people. Using data from the Finnish Prescription Register, the study analysed 62,320 psychotropic drug prescriptions dispensed for people aged ≥ 75 years (n = 52,729) in September 2009. The proportions of prescriptions in which the prescribed dose deviated from one unit per day were assessed for categories and subcategories of psychotropic drugs. The prescription was considered misclassified (a) if the prescribed drug was intended for “as needed” use, (b) if the prescription included a dose range, or (c) if the prescribed dose was below or above one unit per day. Among antidepressants, less than every fourth (23.7%) prescription was misclassified. The proportions of misclassification varied substantially across subcategories, being 13.1% for selective serotonin reuptake inhibitors (SSRIs), 25.3% for other antidepressants and 53.8% for tricyclic antidepressants. Of the benzodiazepine and antipsychotic prescriptions, 79.9% and 57.6%, respectively, were misclassified. In conclusion, the dosage assumption of one unit per day is valid for measuring the legend duration of SSRI and other antidepressant exposures among older people. Among other psychotropic drugs, the dosage assumption is likely to lead to severe exposure misclassification. Copyright