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Anne Paakinaho,1 Miia Tiihonen,1 Heikki Koskela,2,3 Marjaana Koponen,1,4 Jari Tiihonen,5,6 Sirpa Hartikainen,1 Anna-Maija Tolppanen1 1School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland; 2Unit for Medicine and Clinical Research, Pulmonary Division, Kuopio University Hospital, Kuopio, Finland; 3School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland; 4Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia; 5Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; 6Department of Clinical Neuroscience, Karolinska Institutet, and Center for Psychiatry Research, Stockholm City Council, Stockholm, SwedenCorrespondence: Anne Paakinaho, School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, Kuopio, FI-70211, Finland, Tel +358 405408490, Email anne.paakinaho@uef.fiIntroduction: Although β 2-adrenoceptor (β 2AR) agonists have been associated with a lower risk of Parkinson’s disease (PD), the findings are inconclusive and may reflect confounding by indication. We studied the association between inhaled β 2AR agonists and risk of PD in persons with asthma or chronic obstructive pulmonary disease (COPD).Methods: The nested case-control study was conducted within a register-based Finnish Parkinson’s disease study (FINPARK) and included 1406 clinically verified PD cases diagnosed during 1999– 2015, who also had asthma/COPD > 3 years before PD. PD cases were matched with up to seven controls by age, sex, duration of asthma/COPD, pulmonary diagnosis, and region (N = 8630). Cumulative and average annual exposure to short- and long-acting β 2AR agonists before a 3-year lag period was assessed with quartiles of defined daily doses (DDDs). Adjusted odds ratios (aORs) were calculated with 95% confidence intervals (CIs) using conditional logistic regression.Results: Cumulative exposure to either short- or long-acting β 2AR agonists was not associated with a risk of PD. With average annual exposure, a decreased risk was observed only for the highest quartile of long-acting β 2AR agonists (aOR 0.75; 95% CI 0.58– 0.97). In the stratified analysis the lowest risk estimates were observed among those with both asthma and COPD diagnoses. The suggestion of an inverse association was seen for the highest quartile of long-acting β 2AR agonists in asthma.Discussion: Higher levels of exposure to β 2AR agonists were not consistently associated with a reduced risk of PD. The inverse association in the highest category of average annual exposure to long-acting β 2AR agonists may be explained by unmeasured confounding, such as disease severity or smoking.Keywords: Parkinson disease, adrenergic beta-2 receptor agonists, asthma, chronic obstructive pulmonary disease, risk factors

Federica Pisa,1– 3 Jonas Reinold,1– 3 Piia Lavikainen,1,2 Marjaana Koponen,1,2,4 Heidi Taipale,1,2,5,6 Antti Tanskanen,5– 7 Jari Tiihonen,5,6 Sirpa Hartikainen,1,2 Anna-Maija Tolppanen1,2 1School of Pharmacy, University of Eastern Finland, Kuopio, Finland; 2Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland; 3Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany; 4Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia; 5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 6Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland; 7Impact Assessment Unit, National Institute for Health and Welfare, Helsinki, FinlandCorrespondence: Federica PisaBayer, Müllerstrasse 178, Berlin, 13353, GermanyEmail federica.pisa@bayer.comObjective: To determine the risk of hip fracture in persons with Alzheimer´s disease (AD) who initiated antiepileptic drugs (AEDs).Methods: In the Medication use and AD (MEDALZ) cohort of 70,719 Finnish community dwellers with clinically verified incident AD diagnosis in 2005– 2011, we identified all incident users of AEDs using national Prescription register. AEDs were classified as older (valproate, carbamazepine, clonazepam, phenytoin, levetiracetam, primidone) or newer (pregabalin, gabapentin, oxcarbazepine, lamotrigine, topiramate). We matched each user to 2 non-users. Incident hip fractures until 2015 were identified from the Care register for health care. We calculated inverse probability of treatment weighted hazard ratios (HR), with 95% confidence intervals, using Cox regression.Results: Altogether 5522 incident users were identified and matched to 11,044 non-users (in both groups, women: 65%; median age: 81 years). Altogether 53.3% of users initiated with newer AEDs (pregabalin 79.8%, gabapentin 10.2%) while 46.7% initiated with older AEDs (valproate 67.6%, carbamazepine 13.0%). Age- and sex-adjusted IR of hip fracture per 100 person-years was 1.8 (95% CI 1.6– 1.9) in non-users and 2.0 (95% CI 1.8– 2.2) in users. Increased risk of hip fracture was observed in users (HR 1.17, 95% CI 1.05– 1.30) compared with non-users. The risk was higher for short duration of use (< 14 weeks, HR 3.64, 95% CI 2.90– 4.58) than for medium duration (14 to < 64 weeks, HR 1.74, 95% CI 1.48– 2.05) or ≥ 64 weeks’ use (HR 1.23, 95% CI 1.08– 1.40), compared to non-users with same follow-up time. Older AEDs had HR of 1.46 (1.03– 2.08) compared with newer AEDs.Conclusion: Our results imply that AED use is associated with an increased risk of hip fracture in people with AD. These findings prompt careful consideration before prescribing AEDs to persons with AD. Persons with AD treated with antiepileptics should be carefully monitored due to their increased risk of falling and fractures.Keywords: antiepileptic drugs, hip fracture, Alzheimer´s disease, pharmacoepidemiology

Background: According to guidelines, psychotic depression should be treated with both antipsychotics and antidepressants, but current practice is largely unknown. We investigated the prevalence of antipsychotic and antidepressant use in first‐episode psychotic depression and factors related to antipsychotic use after the diagnosis. Methods: We identified individuals aged 16–65 with a first‐episode diagnosis of psychotic depression (ICD‐10 codes F32.3, F33.3) from nationwide data linkage of Finnish healthcare and population registers during 2000–2018. Point prevalence was measured as 2‐week time windows every 3 months, investigating whether the individual had a modeled drug use period ongoing during the window or not, censoring to death and end of data linkage. Results: The study population included 18,490 individuals (58.0% women; mean age 39.9 years, standard deviation 14.7). The prevalence of use for antidepressants (75.0%), antipsychotics (56.4%), and both (50.0%) were highest at 3 months after the diagnosis. The prevalence declined to 51.8%, 34.1%, and 28.7%, respectively, at 3 years after the diagnosis. In a logistic regression analysis, younger age (adjusted odds ratio < 25 vs. ≥55, 0.82 [95% confidence interval 0.73–0.91]), eating disorders (0.78 [0.66–0.92]), substance use disorders (0.80 [0.73–0.87]), and occupational inactivity (0.80 [0.73–0.87]) were associated with decreased odds of using antipsychotics at 3 months after diagnosis. Increased odds were found for diagnosis from inpatient care (1.74 [1.62–1.86]), and later year of cohort entry (2010–2014 vs. 2000–2004, 1.56 [1.42–1.70]). Conclusion: At most, half of the individuals with newly diagnosed psychotic depression used both antidepressants and antipsychotics. This likely has a negative impact on treatment success. [ABSTRACT FROM AUTHOR]

Heidi Taipale,1–4,* Antti Tanskanen,3–5,* Marjaana Koponen,1,2 Anna-Maija Tolppanen,2,6 Jari Tiihonen,3,4 Sirpa Hartikainen1,2,7 1Kuopio Research Centre of Geriatric Care, University of Eastern Finland, 2School of Pharmacy, University of Eastern Finland, Kuopio, Finland; 3Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 4Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, 5National Institute for Health and Welfare, Helsinki, 6Research Centre for Comparative Effectiveness and Patient Safety (RECEPS), University of Eastern Finland, 7Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland *These authors contributed equally to this work. Background: PRE2DUP is a modeling method that generates drug use periods (ie, when drug use started and ended) from drug purchases recorded in dispensing-based register data. It is based on the evaluation of personal drug purchasing patterns and considers hospital stays, possible stockpiling of drugs, and package information. Objective: The objective of this study was to investigate person-level agreement between self-reported drug use in the interview and drug use modeled from dispensing data with PRE2DUP method for various drug classes used by older persons. Methods: Self-reported drug use was assessed from the GeMS Study including a random sample of persons aged ≥75 years from the city of Kuopio, Finland, in 2006. Drug purchases recorded in the Prescription register data of these persons were modeled to determine drug use periods with PRE2DUP modeling method. Agreement between self-reported drug use on the interview date and drug use calculated from register-based data was compared in order to find the frequently used drugs and drug classes, which was evaluated by Cohen’s kappa. Kappa values 0.61–0.80 were considered to represent good and 0.81–1.00 as very good agreement.Results: Among 569 participants with mean age of 82 years, the agreement between interview and register data was very good for 75% and very good or good for 93% of the studied drugs or drug classes. Good or very good agreement was observed for drugs that are typically used on regular bases, whereas “as needed” drugs represented poorer results. Conclusion: PRE2DUP modeling method validly describes regular drug use among older persons. For most of drug classes investigated, PRE2DUP-modeled register data described drug use as well as interview-based data which are more time-consuming to collect. Further studies should be conducted by comparing it with other methods and in different drug user populations. Keywords: Prescription register, pharmacoepidemiology, drug utilization, validation studies

Anna-Maija Tolppanen,1 Heidi Taipale,2,3 Marjaana Koponen,2,3 Piia Lavikainen,2 Antti Tanskanen,4,5 Jari Tiihonen,4–6 Sirpa Hartikainen2,3 1Institute of Clinical Medicine – Neurology, 2Kuopio Research Centre of Geriatric Care, 3School of Pharmacy, University of Eastern Finland, Kuopio, Finland; 4Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden; 5National Institute for Health and Welfare, Helsinki, Finland; 6University of Eastern Finland, Department of Forensic Psychiatry, Niuvanniemi Hospital, Kuopio, Finland Abstract: Memory diseases are the most important determinant of health care service use and quality of life among older individuals. Adverse effects of medication are common among older people, but this age group is underrepresented in clinical trials. Finnish statutory health care and prescription registers, together with personal identification numbers (PINs) and a tax-supported public health plan covering all citizens provide excellent opportunities for epidemiological research. We used routinely collected data from the Finnish health care system to establish the MEDication use among persons with Alzheimer’s disease (MEDALZ-2005) cohort. This cohort study will be used to assess medication use and its effects on health status and hospitalization among persons with Alzheimer’s disease (AD). The cohort includes all community-dwelling persons who had a clinically verified diagnosis of AD, resided in Finland, and were alive on December 31, 2005 and a matched comparison person for each affected individual. Data on purchased prescription medicines (1995–2009), inpatient hospital admissions (1972–2009), outpatient visits (1995–2009), details on diagnosed cancers (1972–2009), and mortality (until October 2010) are available for the whole cohort. This paper describes how this data can be utilized in etiological research and the assessment of health care service use, drug utilization, and associated adverse outcomes in a particularly vulnerable group that is often underrepresented in clinical trials. Keywords: drug utilization, pharmacoepidemiology, epidemiology, cohort