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The Finnish web-based Meds75+ database supports rational, safe and appropriate prescribing to older adults in primary care. This article describes the content and updating process of Meds75+ and demonstrates its applicability in everyday clinical practice. Meds75+ contains a classification (A-D) and recommendation texts for 450-500 drug substances when used in the treatment of older adults aged 75 years or older. The content of Meds75+ is continually updated. Each assessment of a drug substance begins with a structured collection of available information and research evidence. After that, an interdisciplinary expert panel discusses the classification and recommendation using a consensus method. A rolling 3-year updating cycle guarantees that all drug substances are reviewed regularly. Most drug substances are classified as class A (41%) (suitable, e.g. bisoprolol) or as class C (37%) (suitable with specific precautions, e.g. ibuprofen). One-fifth (20%) of the substances are in class D (avoid use, e.g. diazepam). Most commonly, older adults have purchased substances affecting the alimentary tract and metabolism (17%), the nervous system (16%) and the cardiovascular system (15%). In Finland, the proportion of older adults using class D substances (37%) has not changed between the years 2019 and 2022. Meds75+ has potential to support safer and more effective use of medications for older adults, since it offers up-to-date information on drug substances for healthcare professionals., (© 2024. The Author(s).)

Background: Vitamin K antagonists, warfarin in particular, have been the mainstay of anticoagulation therapy, but their use has declined in many countries since direct oral anticoagulants (DOACs) have entered the market., Objective: To examine utilization trends of oral anticoagulants (OACs) in Finland considering the reimbursement of DOACs and changes to national treatment guidelines for the treatment of atrial fibrillation (AF)., Methods: Both public, aggregated data on reimbursed OAC dispensations and individual-level data on electronic dispensations during 2014-2022 were applied. Data on electronic dispensations during 2015-2016 were used to study OAC initiations. Data on entitlements to reimbursement for DOACs came from public data., Results: In 2014, there were almost 20,000 DOAC users, rising to 214,000 in 2022. The number of warfarin users declined since 2015 from over 181,000 to around 59,000 users in 2022, DOACs exceeding warfarin in the number of users in 2019. The total DOAC costs were higher than warfarin costs each year. Rivaroxaban was the most widely used DOAC during 2014-2018, and apixaban during 2019-2022. In 2015, there were more warfarin (56.7%) than DOAC (43.3%) initiators, but the result was opposite for 2016 (warfarin 39.4%, DOACs 60.6%). The number of individuals entitled to reimbursement for DOACs has increased steadily, and in 2022, there were over 196,000 individuals entitled to this reimbursement due to AF., Conclusions: The uptake of DOACs in Finland appears to have been gradual and slower than in many other countries. During the 2010s, the treatment guidelines for AF were more cautious in recommending DOACs than the European guidelines. The use of DOACs increased as their reimbursement became less restrictive., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Emma Aarnio reports a relationship with Merck & Co that includes: consulting or advisory and speaking and lecture fees; a relationship with UCB Pharma that includes: speaking and lecture fees; a relationship with Alk-Abello Nordic that includes: speaking and lecture fees. Janne Martikainen reports a relationship with ESiOR Oy that includes: equity or stocks. Maarit J Korhonen reports a relationship with Oriola Finland Oy that includes: consulting or advisory. Risto Huupponen is the past chairman of the Expert Panel of Meds 75+-database (drug treatment in older subjects) and a member of the Expert Panel for classification of high-risk medicines, both at the Finnish Medicines Agency., (© 2023 The Authors.)

Background: Patient recruitment for clinical trials is challenging-only approximately one third of all trials recruit their participants as planned. The pharmaceutical industry's views on recruitment success have not been comprehensively investigated, although the industry globally conducts almost one third of all clinical drug trials. This study explored patient recruitment success and failure factors and the role of electronic health records (EHR) in the recruitment of trial participants in the Nordic countries., Methods: A descriptive qualitative interview study was conducted with 21 representatives of the pharmaceutical industry or contract research organizations operating in Finland, Sweden, Denmark, and Norway. The interviews covered 34 clinical pre-market drug trials. Qualitative data were analyzed using inductive content analysis., Results: Four main categories were derived to represent both success and failure factors, whereas a fifth category represented only failure factors: (1) sponsor-related (protocol and trial preparation and feasibility evaluations), (2) site/investigator-related (access to patients, motivation, commitment and resources), (3) patient-related recruitment factors (medical need, patients' role in their care and attitudes towards trials), (4) Sponsor-sites-patients collaboration factors, and (5) start-up related factors. EHR was the most important source of recruitment, utilized in 29 out of 34 trials discussed. Revision of the legislation regulating the secondary use of EHR was highlighted as the most effective measure to facilitate the use of EHR in recruitment of trial participants., Conclusions: The industry representatives recognized quite well their own role in contributing to the success or failure of the recruitment: to facilitate recruitment of trial participants, many obstacles can be avoided with better trial preparation and proper feasibility evaluations. As access to patients represents one of the key success or failure factors of recruitment, and as the EHR is regarded the main source of searching for and finding patients, the development of EHR utilization appears to represent a powerful tool to improve patient recruitment., (© 2022. The Author(s).)

Introduction: Feasibility evaluations are performed to create the best possible starting point for the set-up and execution of a clinical trial, and to identify any obstacles for successful trial conduct. New digital technologies can provide various types of data for use in feasibility evaluations. There is a need to identify and compare such data sources for trial site identification and for evaluating the sites' patient recruitment potential. Especially, information is needed on the use of electronic health records. We investigated how different data sources are used by pharmaceutical companies operating in the Nordic countries for identifying trial sites and for evaluating their potential to recruit trial participants., Methods: This was a semi-structured qualitative interview study with 21 participants from pharmaceutical companies and contract research organizations operating in Finland, Sweden, Denmark and Norway. Qualitative content analysis was applied., Results: For identifying countries and trial sites on a global level, the trial sponsors mostly used databases on previous trial performance. The use of electronic health record data was very limited. Sites' and investigators' visibility in various databases was seen as fundamental for their countries becoming selected into new clinical trials. For estimating the sites' recruitment projections, most sites were seen to base their patient count estimates solely on their previous experience. Some sites had reviewed their electronic health record data, which was considered to increase the accuracy of their recruitment estimates and these sites' attractivity. Along with dialogs with investigators, the sponsors used various data sources to validate the investigators' estimates. Legislative obstacles were seen to hinder the use of electronic health record queries for estimation of patient counts., Conclusion: Visibility in the databases used by trial sponsors is crucial for the countries and sites to be identified. Site selection appears to be based on trust and relationships built from experience, but electronic data provide the support upon which the trust is based. Estimation of the number of potential trial participants is a complex and time-consuming process for both investigators and sponsors. Sponsors seem to favour sites who could support their patient count estimates with electronic health record data as they were quicker in providing the estimates and more reliable than sites with no electronic health record evidence. The patient count evaluation process could be simplified, accelerated and made more reliable with more systematic use of electronic health record evidence in the feasibility evaluation phase. This would increase the accuracy of the patient count estimates and, on its part, contribute to improved recruitment success.

Electronic health records (EHR) are a potential resource for identification of clinical trial participants. We evaluated how accurately a commercially available EHR Research Platform, InSite, is able to identify potential trial participants from the EHR system of a large tertiary care hospital. Patient counts were compared with results obtained in a conventional manual search performed for a reference study that investigated the associations of atrial fibrillation (AF) and cerebrovascular incidents. The Clinical Data Warehouse (CDW) of Turku University Hospital was used to verify the capabilities of the EHR Research Platform. The EHR query resulted in a larger patient count than the manual query (EHR Research Platform 5859 patients, manual selection 2166 patients). This was due to the different search logic and some exclusion criteria that were not addressable in structured digital format. The EHR Research Platform (5859 patients) and the CDW search (5840 patients) employed the same search logic. The temporal relationship between the two diagnoses could be identified when they were available in structured format and the time difference was longer than a single hospital visit. Searching for patients with the EHR Research Platform can help to identify potential trial participants from a hospital's EHR system by limiting the number of records to be manually reviewed. EHR query tools can best be utilized in trials where the selection criteria are expressed in structured digital format., (© 2020 The Authors. Published by Elsevier Inc.)

Background: Warfarin is underutilised in frail older people because of the fear of bleeding complications. Drug interactions are an independent bleeding risk factor. However, the extent to which potential drug interactions are taken into account at warfarin therapy initiation in frail patients is not known., Objective: The objective of this study was to investigate the use of potentially interacting drugs increasing the bleeding risk before and after warfarin initiation in frail and non-frail patients., Methods: We conducted an observational study including inpatients aged ≥ 60 years initiated on warfarin in a tertiary hospital in Adelaide, South Australia. Frailty status was assessed with the Reported Edmonton Frail Scale. Medication charts were reviewed before and after warfarin initiation., Results: In total, 151 patients (102 non-frail and 49 frail) were included. Before warfarin initiation, the use of clopidogrel and acetaminophen was more common in frail patients compared with non-frail patients (25.5% vs 10.2%, p = 0.0135, 63.8% vs 35.7% p = 0.0014, respectively). The use of non-steroidal anti-inflammatory drugs, 9.2% in non-frail patients and 6.4% in frail patients before warfarin initiation, was completely stopped after warfarin initiation in both groups. The use of antiplatelet drugs decreased from 56.1% in non-frail patients and 66.0 % in frail patients to 12.2% and 14.9%, respectively. Instead, the use of drugs affecting the metabolism of warfarin or vitamin K increased in both groups. No statistically significant difference was seen in the exposure to interacting drugs between study groups after warfarin initiation. Acetaminophen, senna glycosides and cytochrome P450 2C9 inhibiting drugs were the most common interacting drugs at discharge used in 49.0%, 18.4% and 20.4% of non-frail patients and 53.2%, 29.8% and 19.1% of frail patients, respectively., Conclusions: The overall frequency of potential drug interactions was moderate and frail patients were not exposed to warfarin drug interactions more often than non-frail patients. Further studies in larger study populations are required to verify these results.

Background: Since 1994, the Finnish Prescription Register (FPR) has been the main data source for pharmacoepidemiology research in Finland. However, the FPR data are limited to reimbursed dispensations only. Implementation of electronic prescribing started in 2010 and after a stepwise extension, electronic prescribing became mandatory in all healthcare settings in 2017. Prescriptions issued and dispensed electronically are stored in the Prescription Centre of the nationwide Kanta database., Objectives: To describe the contents of the Kanta database and to compare the coverage of Kanta with the FPR, using prescriptions and dispensations of oral anticoagulants (OACs) as an example., Methods: All prescriptions, dispensations, and their cancellations and corrections for OACs recorded in Kanta were retrieved for the period 2012-2016., Results: In 2016, the total number of valid electronic prescriptions for OACs was 249 139 and the number of valid electronic OAC dispensations was 765 745. The number of identified direct oral anticoagulant (DOAC) users was higher in Kanta compared to the FPR since 2014, although more users of all OACs were identified from the FPR during 2012-2015. In 2016, an indication was identified in 44.7% of OAC prescriptions and dosing instructions in 99.5% of DOAC prescriptions., Conclusions: The Kanta database is a promising source of data on medication exposure. Because of reimbursement restrictions, use of DOACs was under-ascertained through the FPR., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Direct oral anticoagulants provide an alternative to vitamin K antagonists for the anticoagulation therapy in atrial fibrillation (AF). The availability of several treatment options with different attributes makes shared decision-making appropriate for the choice of anticoagulation therapy. The aim of this study was to understand how physicians choose an oral anticoagulant (OAC) for patients with AF and how physicians view patients' participation in this decision. Semi-structured interviews with 17 Finnish physicians (eight general practitioners and nine specialists) working in the public sector were conducted. An interview guide on experience, prescribing and opinions about oral anticoagulants was developed based on previous literature. The data were thematically analysed using deductive and inductive approaches. Based on the interviews, patient's opinion was the most influential factor in decision-making when there were no clinical factors limiting the choice between OACs. Of patient's preferences, the most important was the attitude towards co-payments of OACs. Patients' opinions on monitoring of treatment, dosing and antidote availability were also mentioned by the interviewees. The choice of an OAC in AF was patient-centred as all interviewees expressed that patient's opinion affects the choice., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalization among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person-years of exposure to warfarin-only and 60,253 years of exposure to warfarin-with-statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalization. A Poisson generalized estimating equation model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin-with-statin compared to warfarin-only and to allow multiple episodes per patient and time-dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable-adjusted RR = 0.98, 95% CI 0.89-1.07) or to simvastatin (RR = 1.01, 95% CI 0.91-1.11) with warfarin compared to exposure to warfarin-only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalization., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Introduction: Low adiponectin levels may predict the development of atherosclerosis. We examined the association of childhood adiponectin with preclinical carotid atherosclerosis that is defined as plaque and/or high (≥95th percentile) intima-media thickness (IMT) at the carotid bifurcation in adulthood., Methods: The Cardiovascular Risk in Young Finns Study is a cohort study on cardiovascular risk factors. We used risk factor data from the baseline study (1980) and ultrasound findings from the follow-ups (2001 and 2007). The study population included 1708 participants, aged 3-18 years at baseline., Results: In multivariate analysis, childhood adiponectin was inversely associated with preclinical carotid atherosclerosis: odds ratio 0.68, 95% confidence interval (CI) 0.53-0.86, p = .001, for 1-SD increase in childhood adiponectin after adjusting for childhood non-high-density lipoprotein cholesterol, body mass index, and blood pressure. When examining the incremental predictive ability, we observed that compared to an approach utilizing only conventional risk factors, the model additionally including adiponectin levels improved c-statistics area under curve from 0.733 (95% Cl 0.694-0.771) to 0.748 (95% Cl 0.710-0.786), p = .02., Conclusions: Childhood adiponectin levels improve the prediction of carotid atherosclerosis in adulthood over conventional risk factors. This supports the idea that low adiponectin levels may have a role in the development of preclinical atherosclerosis. Key messages Childhood adiponectin levels improve the prediction of increased carotid intima-media thickness in adulthood over conventional cardiovascular risk factors. These results suggest that adiponectin levels measured in childhood may have a role in the atherosclerotic process.

Background: Previous research shows that low socioeconomic position (SEP; especially low income) is associated with statin nonadherence. We investigated the relationship between SEP and statin adherence in a country with universal coverage using group-based trajectory modeling in addition to the proportion of days covered., Methods and Results: Using data from Finnish healthcare registers, we identified 116 846 individuals, aged 45 to 75 years, who initiated statin therapy for primary prevention of cardiovascular disease. We measured adherence as proportion of days covered over an 18-month period since initiation and identified different adherence patterns based on monthly adherence with group-based trajectory modeling. When adjusted for age, marital status, residential area, clinical characteristics, and copayment, low SEP was associated with statin nonadherence (proportion of days covered <80%) among men (eg, lowest versus highest income quintile: odds ratio, 1.41; 95% confidence interval, 1.32-1.50; basic versus higher-degree education: odds ratio, 1.18; 95% confidence interval, 1.13-1.24; unemployment versus employment: odds ratio, 1.17; 95% confidence interval, 1.10-1.25). Among women, the corresponding associations were different ( P <0.001 for sex-by-income quintile, sex-by-education level, and sex-by-labor market status interactions) and mainly nonsignificant. Results based on adherence trajectories showed that men in low SEP were likely to belong to trajectories presenting a fast decline in adherence., Conclusions: Low SEP was associated with overall and rapidly increasing statin nonadherence among men. Conversely, in women, associations between SEP and nonadherence were weak and inconsistent. Group-based trajectory modeling provided insight into the dynamics of statin adherence and its association with SEP., (© 2016 American Heart Association, Inc.)

Background: The discontinuation of statin medication is associated with an increased risk of cardiovascular and cerebrovascular events and, among high-risk patients, all-cause mortality, but the reasons for discontinuation among statin initiators in clinical practice are poorly understood., Objective: To examine factors predicting the early discontinuation of statin therapy., Methods: In this prospective cohort study, participants with baseline measurements before the initiation of statin treatment were linked to national registers and followed for the discontinuation of statins during the first year of treatment (no filled prescriptions after statin initiation within the subsequent 12 months)., Results: Of all the 9285 statin initiators, 12% (n = 1142) were discontinuers. Obesity, overweight, vascular comorbidities, and older age were independently associated with a reduced risk of discontinuation [odds ratios (OR) = 0.82 (95% confidence interval [CI], 0.69-0.99), 0.85 (95% CI, 0.73-0.98), 0.80 (95% CI, 0.68-0.93), and 0.82 (95% CI, 0.68-0.99), respectively]. In contrast, high-patient cost-sharing was associated with an increased odds (OR = 1.29; 95% CI, 1.03-1.62) for discontinuation. The only significant difference between the sexes (P = .002) was observed among the participants with risky alcohol use, which was associated with a decreased odds for discontinuation among the men (OR = 0.69; 95% CI, 0.49-0.98) and an increased odds among the women (OR = 1.28; 95% CI, 1.02-1.62)., Conclusions: The discontinuation of statin therapy during the first year after initiation is common. Lowering out-of-pocket expenditures and focusing on low-risk patient groups and women with risky alcohol use could help maintain the continuation of medication., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Objectives: Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors., Design: Retrospective cohort study., Setting: Finnish healthcare registers., Participants: Women aged 45-64 years initiating statin use for primary prevention of cardiovascular disease in 2001-2004 (n=42 807)., Outcomes: Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect., Results: During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07)., Conclusions: Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events may be due to the healthy-adherer effect., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

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.

Purpose: We aimed to quantify for the first time the relationship between statin adherence and ischemic stroke (IS) in patients with diabetes., Methods: Using Finnish health registers, we assembled a cohort of 52 868 statin initiators with diabetes in 1995-2006. We conducted a nested case-control analysis matching cases with IS with up to four controls for age, sex, date of statin initiation and follow-up duration. Adjusted rate ratios for IS were estimated with conditional logistic regression. Additional potential confounders were considered with inverse probability weighting and the role of unmeasured confounding using external adjustment. Statin adherence was measured as the proportion of days covered (PDC)., Results: Among 1703 cases and 6799 controls, good adherence to statins (PDC ≥ 80%) was associated with a 23% decreased incidence of IS (95%CI 14-32%) compared with poor adherence (PDC < 80%). This association remained broadly unchanged when stratified by sex, age, history of atherosclerotic cardiovascular disease or IS. There was a dose-response relationship between adherence level and the risk of IS (RR 0.63 [0.53-0.75] for PDC ≥ 80% versus PDC < 20%, P for trend <0.0001). Among patients with good adherence, those initiating with low intensity statin therapy had a 15% lower incidence (95%CI 2-27%) and those initiating with moderate intensity therapy a 29% lower incidence (16-41%) of IS compared with those with poor adherence who initiated with low intensity therapy. Our sensitivity analyses supported the robustness of the results., Conclusions: In diabetes, poor statin adherence may considerably increase the risk of IS both in primary and secondary prevention of IS., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: In previous studies, deficiencies in nursing students' medication competence have been highlighted. However, the focus of research has been limited especially to medication calculation competence and factors associated with it. In order to develop undergraduate nursing education and research, an understanding of the individual and learning environmental factors associated with medication competence from a broader approach is warranted. Our aim was therefore to evaluate the theoretical, practical and decision-making competence of nursing students and to identify factors associated with their medication competence at the beginning and end of their education., Methods: We used a descriptive, correlational study design with a structured instrument including a set of potential associated factors, knowledge test, medication calculation test and patient vignettes. The participants were nursing students at the beginning (n = 328) and at the end of their education (n = 338). Data were analyzed statistically., Results: In the evaluation of theoretical medication competence, the students' mean score over the semesters was 72 % correct answers in a knowledge test. In the evaluation of practical medication competence, the mean score was 74 % correct answers in a medication calculation test. In the evaluation of decision-making competence, the mean score was 57 % correct answers on deciding the best action in the situation given in patient vignettes. At the end of their education, students were able to solve patient vignettes significantly better. Individual factors were most evidently associated with medication competence. At the beginning of their education, students' previous academic success had a stronger association with medication competence. However, at the end of the education students' abilities in self-regulated learning and study motivation were more significant factors., Conclusion: The core elements of medication competence are significantly interrelated, highlighting the need to provide integrated and comprehensive medication education throughout the undergraduate education. Students' learning style is associated with medication competence. There is a need for methods to identify and support students having difficulties to self-regulate their learning. To increase the safety of medication care of patients, research focusing on the development of effective teaching methods is needed. This study produced information for future nursing education research in this field, especially for interventional studies.

Drugs with anticholinergic properties are widely used. However, they may evoke a variety of adverse reactions (such as dry mouth and constipation, but also drowsiness and confusion), and therefore unnecessary use of drugs with anticholinergic properties should be avoided. In particular, older people are particularly vulnerable to the central anticholinergic effects of drugs. However, monitoring of drug-induced anticholinergic effects and drug concentrations in serum is challenging. In addition to the 'pure' anticholinergics such as atropine and oxybutynin, several other drugs whose principal mode of action is not anticholinergic, possess anticholinergic properties, thus increasing the risk of anticholinergic adverse effects. In this paper, we focus on the central anticholinergic effects of drugs, and on the usefulness of the serum anticholinergic assay (SAA) in the prediction of anticholinergic effects. Results on the anticholinergic effects of drugs on cognition are mixed. This may be because of differences in the populations as well as in the drugs used. In addition, the clinical conditions of the patients may affect the results. The SAA has been used in an attempt to measure anticholinergic burden. However, the results are variable and the SAA levels do not necessarily reflect the medication used by the patient. Therefore, its usefulness in determining anticholinergic adverse reactions is questionable.

Objectives: To assess the extent to which adherence to statins is associated with the incidence of cardiovascular (CV) events and all-cause mortality in the primary prevention of CV diseases and whether different analytical approaches influence the observed associations., Methods: This population-based cohort study used data from Finnish registers. The cohort included 97,575 new statin users aged 45 to 75 years in 2001 to 2004 with no CV diseases at baseline. Exposure was defined as adherence to statins (proportion of days covered [PDC]). The primary outcome was any CV event or death during a 3-year follow-up. Different analytical approaches, including multivariable-adjusted Cox regression, inverse probability weighting with time-varying adherence, and propensity score calibration, were used., Results: During the first year of follow-up, 53% displayed good (PDC ≥80%), 26% had intermediate (PDC 40%-79%), and 21% exhibited poor (PDC <40%) adherence. After adjustment for sociodemographic and clinical covariates, a 25% relative risk reduction (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.71-0.79) was observed in the rate of any CV event or death among good versus poor adherers. Good adherers also had a lower incidence than poor adherers of acute coronary syndrome (HR 0.56; 95% CI 0.49-0.65) and acute cerebrovascular disease events (HR 0.67; 95% CI 0.60-0.76). The different analytical approaches achieved comparable results for all the outcomes., Conclusions: The incidence of CV events and mortality was higher in poor versus good adherers. Different analytical methods that took into account changes in adherence and confounding at baseline did not appreciably affect the results., (Copyright © 2015. Published by Elsevier Inc.)

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., (© 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Purpose: Due to potential drug-drug interactions and subsequent bleeding risk, analgesic use should be reviewed when an oral anticoagulant is initiated. The aim of this study was to compare use of non-steroidal anti-inflammatory drugs (NSAIDs) and other analgesics before and after oral anticoagulant initiation., Methods: All individuals who initiated warfarin, dabigatran, or rivaroxaban between January 2012 and September 2013 were identified from the Finnish Prescription Register. Prevalence of analgesic use during 3 months after oral anticoagulant initiation was compared to analgesic use during 4 months before initiation. Analgesics included were NSAIDs, paracetamol, paracetamol in doses ≥ 2 g/day, tramadol, and other opioids. Conditional logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI)., Results: In total, 54,025 initiated warfarin, 16,894 rivaroxaban, and 1569 dabigatran. The odds of NSAID use decreased among warfarin initiators (odds ratio (OR) 0.10; 95% confidence interval (CI) 0.09-0.10); 2.6% used NSAID after initiation. In contrast, the odds of NSAID use increased among rivaroxaban (OR 3.56; 95% CI 3.37-3.75) and dabigatran initiators (OR 1.44; 95% CI 1.16-1.78). The proportions using NSAIDs after the initiation were 69 and 32%, respectively. However, NSAID use decreased among dabigatran initiators with confirmed atrial fibrillation (OR 0.46; 95% CI 0.23-0.92) and among rivaroxaban initiators with a daily dose of ≥ 15 mg (OR 0.28; 95% CI 0.19-0.40)., Conclusions: The use of NSAIDs decreases extensively among warfarin initiators which is encouraging. However, the use of NSAIDs increases among rivaroxaban and dabigatran initiators. This is a concern as the bleeding risk may increase due to potential pharmacodynamic interactions.

Objective: To estimate the cost-effectiveness of statin therapy for primary prevention of coronary heart disease (CHD) events under real-world adherence., Methods: A cost-effectiveness model was applied to estimate the expected 10-year costs and health outcomes (in terms of quality-adjusted life-years, QALYs) associated with and without statin treatment (at defined adherence levels) among hypothetical cohorts of Finnish men and women who were initially without established CHD. Treatment efficacy, cost, and quality of life estimates were obtained from published sources. Long-term treatment adherence was measured based on data from the national prescription register., Results: At an assumed willingness-to-pay threshold of €20,000 per QALY gained, statin treatment with real-world adherence was cost-effective among the older patient groups when the patients' 10-year CHD risk was as high as 20% and did not seem cost-effective in the youngest age groups. Conversely, statin treatment with full adherence was cost-effective for almost all patient groups with a 10-year CHD risk of at least 15%., Conclusions: Even though generic statins are now low-cost drugs, treatment adherence seems to have a major impact on the cost-effectiveness of statin treatment in primary prevention. This finding stresses the importance of making a concerted effort for improving adherence among patients on statin therapy to obtain full benefit of the investment in statins. Therefore, novel cost-effective approaches to improve treatment adherence are warranted., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To characterize accumulation of drug-modifiable cardiovascular (CV) risk factors in statin initiators who had no prior medication or hospitalizations for CV disease or diabetes., Methods: A cohort of 45-75-year-old statin initiators in Finland with no prior CV diseases, diabetes or medication for these conditions was followed up for 24 months after statin initiation for accumulation of CV and diabetes drugs. The number of drugs was measured semi-annually since the first statin purchase and analyzed by growth mixture modeling., Results: Of the 11 948 apparently healthy statin initiators, 34% purchased at least one additional CV or diabetes drug during the subsequent 24 months. Of those, 20% redeemed no other CV or diabetes drugs at statin initiation but started to accumulate them after 18 months of follow-up, receiving on average 1.3 other drugs at 24 months. The majority, 59%, redeemed on average 0.5 drugs at statin initiation and accumulated 1.5 drugs by the end of 24-month follow-up. Seventeen percent received 1 additional drug at statin initiation, accumulating on average 3 drugs. The remaining 4% with an average of 2 CV or diabetes drugs at statin initiation redeemed 3.5 additional drugs during the follow-up., Conclusions: Two years after statin initiation, 2 in 3 apparently healthy initiators could still be defined as such as reflected by CV and diabetes medication use.

Background: Easily detectable predictors of nonadherence to long-term drug treatment are lacking. We investigated the association between lifestyle factors and nonadherence to statin therapy among patients with and without cardiovascular comorbidities., Methods: We included 9285 participants from the Finnish Public Sector Study who began statin therapy after completing the survey. We linked their survey data with data in national health registers. We used prescription dispensing data to determine participants' nonadherence to statin therapy during the first year of treatment (defined as < 80% of days covered by filled prescriptions). We used logistic regression to estimate the association of several lifestyle factors with nonadherence, after adjusting for sex, age and year of statin initiation., Results: Of the participants without cardiovascular comorbidities (n = 6458), 3171 (49.1%) were nonadherent with their statin therapy. Obesity (adjusted odds ratio [OR] 0.86, 95% confidence interval [CI] 0.74-0.99), overweight (adjusted OR 0.88, 95% CI 0.79-0.98) and former smoking (adjusted OR 0.82, 95% CI 0.74-0.92) predicted a reduced risk of nonadherence in this group after adjustment for sex, age and year of statin initiation. Of the participants with cardiovascular comorbidities (n = 2827), 1155 (40.9%) were nonadherent. In this group, high alcohol consumption (adjusted OR 1.55, 95% CI 1.12-2.15), extreme drinking occasions (adjusted OR 1.48, 95% CI 1.11-1.97) and a cluster of 3-4 lifestyle risks (adjusted OR 1.61, 95% CI 1.15-2.27) predicted increased odds of nonadherence after adjustment for sex, age and year of statin initiation., Interpretation: People with cardiovascular comorbidities who had risky drinking behaviours or a cluster of lifestyle risks were at increased risk of nonadherence. Among individuals without cardiovascular comorbidities, information on lifestyle factors was unhelpful in identifying those at increased risk of nonadherence; that overweight, obesity and former smoking were predictors of better adherence in this group provides insight into mechanisms of adherence to preventive medication that deserve further study., (© 2014 Canadian Medical Association or its licensors.)

Objective: To assess the representativeness of the Heart Protection Study (HPS) and the Collaborative Atorvastatin Diabetes Study (CARDS) for incident statin users., Design: A population-based analysis with linked register data., Setting: Finland., Population: 56 963 patients with diabetes initiating statin use from 2005 to 2008., Main Outcome Measures: We determined the proportions of real-world patients who fulfilled the eligibility criteria for HPS and CARDS trials and assessed the cardiovascular disease (CVD) event rates, assumed to reflect the background CVD risk, for those eligible and ineligible. We used descriptive statistics to identify the patient characteristics, lipid-lowering interventions and adherence to statin therapy., Results: Of the real-world patients, 57% (N=32 582) fulfilled the eligibility criteria for HPS (DM) and 49% (N=20 499) of those without CVD for CARDS. The patients ineligible for HPS (DM) had a higher cumulative risk for CVD events than those eligible, whereas regarding CARDS the cumulative risks were of similar magnitude. The overall CVD event rates seemed to be comparable to those in the reviewed trials. Both trials were under-representative of women and users of antihypertensive agents and metformin. 27% and 29% of real-world patients had an initial statin dose corresponding to <20 mg of simvastatin. The proportions of patients who were deemed adherent were 57% in the real world and 85% in both trials., Conclusions: Only half of the real-world patients would have qualified for the HPS (DM) and CARDS, limiting their representativeness for clinical practice. Women and users of antihypertensive agents and metformin were under-represented in both trials. These deviations reflect the changes in diabetes treatment over the years and are not expected to modify the average treatment effects of statins on CVD. Prescribing of lower statin doses in clinical practice than used in the trials and lower adherence may, however, attenuate the benefits in the real world., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: The benefits of statin treatment initiated in advanced age are largely unknown; however, good adherence to treatment is essential for beneficial effects to be achieved also when treating older people. This study characterizes older statin initiators, including their cardiovascular risk profiles and morbidity, and investigates patterns of treatment persistence., Methods: Longitudinal register-based study. All statin initiators in Finland aged ≥70 in 2000-2008 (n = 157,709) were identified from the nationwide Prescription Register. Using information from comprehensive health registers, the initiators were classified as having low, moderate, or high cardiovascular risk. For the initiators in 2000 and 2004, patterns of persistence were evaluated over a 4-year follow-up using the anniversary method., Results: The annual number of statin initiators increased from 15,082 to 19,728; the proportion of those aged ≥80 increased from 12.9 to 25.8 %. The prevalence of coronary heart disease at statin initiation decreased from 45.5 to 28.1 %. Only every tenth initiator (9.2-11.7 %) was estimated to have low cardiovascular risk each year. Four in five initiators (76.9-80.5 %) persisted with statin treatment after 1 year. The probability to survive and remain persistent for 4 years was 51.6 % and the probability to discontinue within the first year without restarting in the subsequent 3 years was 9.1 %. There were no noticeable differences in persistence across the risk groups., Conclusions: Long-term persistence with statins among older people was good across cardiovascular risk groups. These findings are consistent with the notion that the decision on long-term continuation of statin use is made during the first year of treatment.

Background: Sequential cohort design (SCD) applying matching for propensity scores (PS) in accrual periods has been proposed to mitigate bias caused by channeling when calendar time is a proxy for strong confounders. We studied the channeling of patients according to atorvastatin and simvastatin initiation in Finland, starting from the market introduction of atorvastatin in 1998, and explored the SCD PS approach to analyzing the comparative effectiveness of atorvastatin versus simvastatin in the prevention of cardiovascular events (CVE)., Methods: Initiators of atorvastatin or simvastatin use in the 45-75-year age range in 1998-2006 were characterized by their propensity of receiving atorvastatin over simvastatin, as estimated for 17 six-month periods. Atorvastatin (10 mg) and simvastatin (20 mg) initiators were matched 1∶1 on the PS, as estimated for the whole cohort and within each period. Cox regression models were fitted conventionally, and also for the PS matched cohort and the periodically PS matched cohort, to estimate the hazard ratios (HR) for CVEs., Findings: Atorvastatin (10 mg) was associated with a 11%-12% lower incidence of CVE in comparison with simvastatin (20 mg). The HR estimates were the same for a conventional Cox model (0.88, 95% confidence interval 0.85-0.91), for the analysis in which the PS was used to match across all periods and the Cox model was adjusted for strong confounders (0.89, 0.85-0.92), and for the analysis in which PS matching was applied within sequential periods (0.88, 0.84-0.92). The HR from a traditional PS matched analysis was 0.80 (0.77-0.83)., Conclusions: The SCD PS approach produced effect estimates similar to those obtained in matching for PS within the whole cohort and adjusting the outcome model for strong confounders, but at the cost of efficiency. A traditional PS matched analysis without further adjustment in the outcome model produced estimates further away from unity.

Medication management is one of the fundamental roles of nurses. Deficiencies in registered nurses' medication competence have been highlighted in previous research. It is important to ensure adequate medication competence to ensure safe practice upon graduation to nursing profession. Yet, little is known of the current medication education in undergraduate nursing programmes. This study aims to describe the current medication education in Finland. More precisely, we explored the curriculum content, teaching and evaluation methods. A national survey in which data was collected with two questionnaires was conducted: one targeted programme managers responsible for curriculum (n = 22) and the other one teachers (n = 136) involved with medication education. The data was analyzed statistically. The amount of medication education varied between the polytechnic schools involved. It appears that the content of teaching is quite comprehensive. However, we found under-emphasis on theoretical basis of medication care. This result is worrying since the understanding of the principles is essential for safe delivery of medication care. Also more emphasis on the use of self-treatment medications and therefore on patient education is warranted. The most often used teaching methods were lectures and skill laboratories. In all of the polytechnic schools, nurse students' medication competence was regularly evaluated. Based on previous research, there is scope for educational initiatives to improve nurse students' medication competence. Therefore, it is important to develop medication education to ensure that medication education with relevant content and with contemporary and evidence-based methods is provided during nurses' basic education.

Aims: Clopidogrel is a prodrug that needs to be activated to inhibit platelet aggregation. The objective of this study was to evaluate the prevalence and clinical consequences of potential drug-drug interactions of clopidogrel with drugs affecting CYP3A4 activity., Methods: Co-administrations of clopidogrel together with well-established CYP3A4 inhibitors, CYP3A4 inducers, and atorvastatin were investigated in a population-based pharmacoepidemiological study utilizing data from the national healthcare registers and in more detail from a university hospital register in Finland. The main outcome measures were all-cause mortality and mortality and morbidity related to thrombosis or bleeding., Results: In the nationwide analysis, 6.1%, 1.0%, and 20.8% of the clopidogrel-treated patients were exposed to concomitant use of CYP3A4 inhibitors, CYP3A4 inducers, and atorvastatin, respectively. In the survival analysis, the adjusted hazard ratio for overall mortality was 2.29 (P < 0.001) for CYP3A4 inducer users and 0.74 (P = 0.003) for atorvastatin users compared with controls (patients receiving clopidogrel without interacting medication). CYP3A4 inhibitor use seemed to prevent from thrombosis: HR 0.67, P < 0.001. The hospitalizations due to bleedings were rarer in atorvastatin and CYP3A4 inhibitor groups compared with controls. Thrombosis complications leading to hospitalizations were more often seen in the atorvastatin group than in the control group., Conclusions: No uniform untoward effect of concomitant CYP3A4 inhibitor use on the clinical efficacy of clopidogrel was found. In patients receiving concomitant atorvastatin and clopidogrel, the antithrombotic effect of clopidogrel was moderately attenuated, but the combination significantly reduced the overall mortality. CYP3A4 inhibitors and atorvastatin may reduce bleedings in clopidogrel users., (© 2013 John Wiley & Sons Ltd.)

Background: The extent to which common life transitions influence medication adherence among patients remains unknown. We examined whether retirement is associated with a change in adherence to medication in patients with hypertension or type 2 diabetes., Methods: Participants in the Finnish Public Sector study were linked to national registers. We included data for the years 1994-2011. We identified and followed 3468 adult patients with hypertension and 412 adult patients with type 2 diabetes for medication adherence for the 3 years before their retirement and the 4 years after their retirement (mean follow-up 6.8 yr). Our primary outcome was proportion of patients with poor adherence to medication, which we defined as less than 40% of days covered by treatment. We determined these proportions before and after retirement using data from filled prescriptions., Results: The preretirement prevalence of poor adherence to medication was 6% in men and women with hypertension, 2% in men with diabetes and 4% in women with diabetes. Among men, retirement was associated with an increased risk of poor adherence to both antihypertensive agents (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.03-1.68) and antidiabetic drugs (OR 2.40, 95% CI 1.37-4.20). Among women, an increased risk of poor adherence was seen only for antihypertensive agents (OR 1.25, 95% CI 1.07-1.46). Similar results were apparent for alternative definitions of poor adherence. Our results did not differ across strata of age, socioeconomic status or comorbidity., Interpretation: We found a decline in adherence to medication after retirement among men and women with hypertension and men with type 2 diabetes. If these findings can be confirmed, we need randomized controlled trials to determine whether interventions to reduce poor adherence after retirement could improve clinical outcomes of treatments for hypertension and 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., (© 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.)

Background: Orthostatic hypotension (OH) is associated with significant morbidity and mortality among older people. We have studied whether its prevalence can be reduced by a Comprehensive Geriatric Assessment (CGA)., Study Design and Setting: 1000 randomly-selected persons aged ≥75 years were divided into intervention (n = 500) and control groups (n = 500). We focused on those subjects in whom an orthostatic blood pressure test had been performed at least once during the study period (2004-2007) (n = 365 and 332 for intervention and control groups, respectively). A CGA, including evaluation of the adequacy of the medication, was performed annually in the intervention group but not in the control group. We conducted Markov models to study change in the OH profiles and the effect of CGA on it. Competing risk of mortality was modeled as an absorbing state to avoid attrition bias., Results: Over 3 years, the prevalence of OH decreased (35.0% → 28.0%) in the intervention group, whereas its prevalence increased in the control group (32.8% → 40.8%). By Markov models it was shown that CGA had a statistically significant effect on recovering from OH. In addition, CGA was shown to protect from developing OH., Conclusions: Repeated CGA performed annually can reduce the prevalence of OH.

Background: The serum anticholinergic activity (SAA) assay has been used to quantify patients' anticholinergic load. In addition, several ranked lists of anticholinergic drugs have been developed to assess anticholinergic drug burden., Objective: This study investigated whether SAA assay results and scores from three ranked lists of anticholinergic drugs (Carnahan's Anticholinergic Drug Scale, Rudolph's Anticholinergic Risk Scale, and Chew's list) are associated with anticholinergic adverse drug events (ADEs) in older people., Methods: We analyzed data from participants in the population-based Geriatric Multidisciplinary Good Care of the Elderly Study in Kuopio, Finland (n = 621). Demographic, diagnostic, and drug use data were collected during standardized interviews and verified from medical records. Vision, functional capacity, cognition, and mood were assessed using validated techniques. The SAA was measured from blood samples., Results: The SAA was not associated with anticholinergic ADEs. Anticholinergic drug burden computed using each of the three lists was inversely associated with short-distance vision (p < 0.01), activities of daily living (p < 0.05), and instrumental activities of daily living (p < 0.05) in persons with and without dementia. Furthermore, poorer Mini Mental State Examination and poorer Geriatric Depression Scale scores were associated with the anticholinergic drug burden in persons without dementia (p < 0.05-p < 0.001). The association between anticholinergic drug burden and ADEs was strongest when using the lists developed by Carnahan and Chew., Conclusions: Scores obtained from ranked lists of anticholinergic drugs were associated with clinically significant anticholinergic ADEs but the SAA was not. This finding supports the usefulness of these lists to help identify patients at risk of anticholinergic ADEs in clinical practice.

Purpose: Statin use has increased in older age groups, although there is little evidence for the benefits of statin therapy in the elderly, especially in low-risk persons. The aim of this paper is to describe recent trends in the prevalence and incidence of statin use among the Finnish older population, according to the person's estimated cardiovascular (CV) event risk., Methods: We conducted a register study covering the whole community-dwelling population of Finland, aged >70 years in 2000-2008 (N = 883,051). Data on reimbursed purchases of statins, antidiabetic and CV drugs, and pre-existing CV diseases were retrieved from comprehensive national registers. We stratified each person into low, moderate or high CV risk category, and according to age (70-74, 75-79, and >80 years) and sex., Results: Between 2000 and 2008, the age-sex-standardized prevalence of statin use tripled from 12.2 % to 38.7 % (rate ratio 3.0, 95 % CI 3.0-3.1), and the incidence almost doubled (from 3.7 % to 6.8 %; rate ratio 1.8, 95 % CI 1.8-1.9). The prevalence and incidence of statin use were consistently highest among high-risk persons. The greatest relative increases were observed in persons aged >80 years and in those at low risk; however, the proportion of statin users at low CV risk remained the same (∼7 % of all users)., Conclusions: Statin prescribing is shifting towards older age groups. A substantial increase in prevalence and incidence was seen across all risk categories, but the channeling of statin use towards high-risk persons remained unchanged.

Objective: Physical activity (PA) may reduce the risk of coronary heart disease (CHD) by inducing beneficial changes in several risk factors. We studied the associations between PA and a range of risk markers of CHD in young adults., Methods and Results: We measured serum lipoproteins, oxidized LDL, adipokines, inflammatory markers, metabolic markers, and arginine metabolites in 2,268 individuals (age 24-39 y). Participants were asked frequency, duration, and intensity of PA in leisure time. In addition, commuting to work was assessed. In both sexes, PA was inversely associated with waist circumference (all P < 0.0001). After controlling for sex, age, and waist circumference, PA was directly associated with HDL-cholesterol and apolipoprotein A1, and inversely with heart rate, smoking, oxidized LDL, apolipoprotein B, insulin, glucose, C-reactive protein, leptin, L-arginine, and phospholipase A2 activity (all P < 0.05)., Conclusion: These population-based data are consistent with the idea that the beneficial effects of PA on CHD risk are mediated by favorable influences on several risk factors, as judged by independent relations to markers of lipoprotein metabolism, glucose metabolism, and inflammation. These associations reflect beneficial effects on cardiovascular health in both sexes and may offer mechanistic insights for the inverse association between PA and CHD.

Aims: Hypofibrinolysis displayed by elevated serum plasminogen activator inhibitor 1 (PAI-1) level has been associated with cardiovascular disease (CVD) and its risk factors such as obesity and insulin resistance. However, no studies have examined associations between PAI-1 and CVD risk factors in healthy subjects. We examined associations between serum PAI-1, ultrasound markers of atherosclerosis and CVD risk factors and whether PAI-1 improves prediction of atherosclerosis over known risk factors in a cohort of asymptomatic adults., Methods: We analyzed PAI-1 and CVD risk factors and assessed carotid intima-media thickness (cIMT), distensibility (CDist) and the presence of a carotid atherosclerotic plaque and flow-mediated dilation (FMD) ultrasonographically for 2202 adults (993 men and 1,209 women, aged 30-45 years) participating in the ongoing longitudinal cohort study, The Cardiovascular Risk in Young Finns Study. High cIMT was defined as >90th percentile and/or carotid plaque and low CDist and low FMD as <20th percentile., Results: In bivariate analyses, PAI-1 correlated directly with cIMT and the risk factors: blood pressure, BMI, waist and hip circumference, alcohol use, total and LDL-cholesterol, triglycerides, glomerular filtration rate, high-sensitivity CRP and glucose (all P<0.005). PAI-1 was higher in men and increased with age. Inverse correlation was observed with CDist, HDL-cholesterol and adiponectin in both sexes, with testosterone and sex hormone binding globulin in men and with creatinine and oral contraceptive use in women (P<0.005). Independent direct associations were observed between PAI-1 and waist circumference, serum triglycerides, insulin, alcohol use and age and inverse with serum creatinine, HDL-cholesterol and adiponectin. PAI-1 did not improve estimation of high cIMT, low CDist and low FMD over conventional risk factors (P for difference in area under curve ≥ 0.37)., Conclusion: PAI-1 was independently associated with several known CVD risk factors, especially obesity markers, in both men and women. However, addition of PAI-1 to known risk factors did not improve cross-sectional prediction of high cIMT, low CDist and low FMD suggesting that PAI-1 is not a clinically important biomarker in early atherosclerosis., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background and Methods: Serum uric acid (SUA) is a suggested biomarker for established coronary artery disease, but the role of SUA in early phases of atherosclerosis is controversial. The relations of SUA with vascular markers of subclinical atherosclerosis, including carotid artery intima-media thickness (cIMT), carotid plaque, carotid distensibility (Cdist) and brachial flow-mediated dilatation (FMD) were examined in 1985 young adults aged 30-45 years. In addition to ordinary regression, we used Mendelian randomization techniques to infer causal associations., Results: In women, the independent multivariate correlates of SUA included BMI, creatinine, alcohol use, triglycerides, glucose and adiponectin (inverse association) (Model R(2) = 0.30). In men, the correlates were BMI, creatinine, triglycerides, C-reactive protein, alcohol use, total cholesterol and adiponectin (inverse) (Model R(2) = 0.33). BMI alone explained most of the variation of SUA levels both in women and men (Partial R(2) ∼ 0.2). When SUA was modeled as an explanatory variable for vascular markers, it directly associated with cIMT and inversely with Cdist in age- and sex-adjusted analysis. After further adjustments for BMI or glomerular filtration rate, these relations were reduced to non-significance. No associations were found between SUA and FMD or the presence of a carotid plaque. Mendelian randomization analyses using known genetic variants for BMI and SUA confirmed that BMI is causally linked to SUA and that BMI is a significant confounder in the association between SUA and cIMT., Conclusion: SUA is associated with cardiovascular risk markers in young adults, especially BMI, but we found no evidence that SUA would have an independent role in the pathophysiology of early atherosclerosis., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Aim: The aim of this review was to identify factors associated with nurse students' medication competence., Background: Registered nurses play an important role in safe and effective medication management. Previous nursing literature has highlighted deficiencies in nurse students' medication competence, yet little is known about specific factors which are associated with their medication competence., Method: Integrative literature review., Results: Nineteen articles met the selection criteria for this review. The main competence area the reviewed articles focused on was medication calculation skills of nurse students. However, a total of twelve factors were identified to be associated with nurse students' medication competence. They constitute three main categories: factors associated with individual nurse students' particular circumstances, the clinical learning environment, and the educational institution. Individual factors such as students' attitudes towards mathematics and their self-confidence seem to be associated most strongly with medication competence., Conclusion: First, based on this review, the focus in medication competence research has been strongly on nurse students' medication calculation skills. Therefore, in future research and practice, attention needs to be paid to other competency areas as well, such as medication administration and patient medication education skills. Second, overall, only a limited amount of research exists that explores what factors are associated with medication competence., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: We examined whether metabolic syndrome (MetS) predicts increased alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) levels in young adults, whether spontaneous recovery from MetS has a favorable effect on liver enzyme activities, and whether these enzymes contribute to the atherogenicity of MetS (assessed by carotid intima-media thickness (IMT))., Methods: The study included 1,553 subjects (base-line age 31.5 ± 5.0 years). ALT and GGT were measured in 2007. MetS was diagnosed by the new Joint Interim Societies definition., Results: ALT and GGT levels were higher in subjects with MetS compared to those without in 2007. The association was independent of alcohol intake and BMI. In multivariable models adjusted for base-line age, LDL cholesterol, CRP, alcohol intake, and adiponectin, MetS in 2001 predicted increased ALT (β ± SEM = 0.320 ± 0.062, P < 0.0001 in men; 0.134 ± 0.059, P = 0.02 in women) and GGT (β ± SEM = 0.222 ± 0.067, P < 0.0001 in men; 0.236 ± 0.060, P < 0.0001 in women) levels after 6 years. Subjects with MetS only at base-line (2001) had lower ALT levels after 6 years compared to subjects with persistent and incident MetS. No statistically significant interaction for MetS*ALT (P = 0.81) or MetS*GGT (P = 0.92) on IMT was observed., Conclusion: In young adults MetS may induce liver enzyme changes that indicate increased risk of non-alcoholic fatty liver disease, but we found no evidence that increased enzyme levels would amplify the atherogenicity of MetS.

What Is Known and Objective: Out-of-pocket expenses of drug therapy may negatively affect adherence. We aimed to analyse 1-year discontinuation rates between cohorts initiating therapy with either generic simvastatin or non-generic atorvastatin., Methods: Statin-naìve initiators of atorvastatin and generic simvastatin in April-June 2003, and corresponding cohorts in 2005, were identified through the nationwide Finnish prescription register. Persistence with statin therapy was followed for 365 days, considering the treatment to have been discontinued when the tablet-free gap between two consecutive refills exceeded 90 days. Using multivariate-adjusted logistic regression, odds ratios (OR) for discontinuation associated with initiating with simvastatin vs. atorvastatin were estimated separately for each year., Results and Discussion: In the year 2003, 5838 persons initiated treatment with atorvastatin and 5644 with generic simvastatin. In the year 2005, the respective numbers were 5228 and 10 987. Soon after the introduction of generic substitution in 2003, there was no difference in the risk of discontinuation between the comparator groups [OR 0·97, 95% confidence interval (CI) 0·89-1·05]. Two years later, persons initiating with generic simvastatin were 20% less likely to discontinue statin therapy (OR 0·80; 95% CI 0·74-0·83). Among persons whose medicinal costs were almost completely reimbursed towards the end of the initiation year, the OR was 1·14 (95% CI 0·76-1·64, P = 0·033 for interaction)., What Is New and Conclusions: We found that lower out-of-pocket expenses associated with the initiating statin had a positive impact on persistence with therapy. The finding does not seem to apply to persons with minor copayments towards the end of the initiation year., (© 2011 Blackwell Publishing Ltd.)

Objective: To study the association of long-term statin use and the risk of low-energy hip fractures in middle-aged and elderly women., Design: A register-based cohort study., Setting: Finland., Participants: Women aged 45-75 years initiating statin therapy between 1996 and 2001 with adherence to statins ≥ 80% during the subsequent five years (n = 40,254), a respective cohort initiating hypertension drugs (n = 41 610), and women randomly selected from the population (n = 62 585)., Main Outcome Measures: Incidence rate of and hazard ratio (HR) for low-energy hip fracture during the follow-up extending up to 7 years after the 5-year exposure period., Results: Altogether 199 low-energy hip fractures occurred during the 135 330 person-years (py) of follow-up in the statin cohort, giving an incidence rate of 1.5 hip fractures per 1000 py. In the hypertension and the population cohorts, the rates were 2.0 per 1000 py (312 fractures per 157,090 py) and 1.0 per 1000 py (212 fractures per 216 329 py), respectively. Adjusting for a propensity score and individual variables strongly predicting the outcome, good adherence to statins for five years was associated with a 29% decreased risk (HR 0.71; 95% CI 0.58-0.86) of a low-energy hip fracture in comparison with adherent use of hypertension drugs. The association was of the same magnitude when comparing the statin users with the population cohort, the HR being 0.69 (0.55-0.87). When women with poor (<40%), moderate (40 to 80%), and good adherence (≥ 80%) to statins were compared to those with good adherence to hypertension drugs (≥ 80%) or to the population cohort, the protective effect associated with statin use attenuated with the decreasing level of adherence., Conclusions: 5-year exposure to statins is associated with a reduced risk of low-energy hip fracture in women aged 50-80 years without prior hospitalizations for fractures.

Purpose: Knowledge of the different usage patterns that emerge during a long-term statin therapy is limited. The aim of this study was to characterize statin use, including the rates of reinitiation after extended periods of non-use, transitions between good and poor adherence, and the effect of the length of a drug-free period on the identification of new users., Methods: The study cohort comprised individuals aged 45-84 years who were identified in the Finnish prescription register as having purchased statins between 1997 and 2007. New users in 1997, including those with no statin purchases during the preceding 3 years, were followed-up until institutionalization, death, or 31 December 2007. Reinitiation rates after ≥180 days with no refill for statins were analyzed using survival analysis. Annual adherence levels and the prevalences of good (proportion of days covered ≥0.80) and poor (<0.80) adherence were calculated for ten 1-year periods following initiation. For statin users in 2007, purchases were captured over the previous 10 years., Results: Based on the data extracted from the Finnish prescription register, 32,760 persons initiated statin treatment in 1997, of whom 48.1% had discontinued it for at least 180 days by the end of the follow-up period. Of the discontinuers, 46.7% restarted the treatment within 1 year and 88.7% by the end of the follow-up. Of those followed up for ≥10 years, 51.8% had ≥6 years of treatment with good adherence. In 2007, 27.7% of the initiators having no statin purchases within the previous year had refills during the preceding 10 years., Conclusion: Statin use is dynamic. This should be taken into consideration in clinical practice and when studying the incidence, patterns, and health outcomes of statin use.

Background: Increased levels of C-reactive protein (CRP) and serum amyloid A (SAA) are associated with an increased risk of cardiovascular disease. It is hypothesized that dysregulation of the autonomic nervous system (ANS) leads to increased inflammation via the cholinergic anti-inflammatory pathway. Heart rate variability (HRV) is a marker of ANS function. HRV has been shown to be associated with CRP levels. Currently, there are no studies addressing the relationship between HRV and SAA., Design: The purpose of this study was to compare the associations between HRV, CRP and SAA in healthy young adults. CRP and SAA concentrations and short-term HRV indices [high frequency (HF), low frequency (LF), total spectral component of HRV, root mean square differences of successive R-R intervals, the standard deviation of all R-R intervals and ratio between LF and HF) were measured in 1601 men and women aged 24-39 taking part in the Cardiovascular Risk in Young Finns study., Results: A significant inverse correlation (P < 0·05) between HRV indices and inflammatory markers was observed. However, in linear regression analyses, only inverse association between HRV indices and CRP levels remained significant (P < 0·05), while association between HRV indices and SAA levels was attenuated to the null (P > 0·05) after adjusting for age, sex, body mass index, cholesterol levels, leptin and other common traditional cardiovascular risk factors., Conclusions: Reduced HRV indices are independently associated with increased CRP levels, but not with SAA levels. This association supports the hypothesis that dysregulation of the ANS may lead to increased inflammation early in adulthood., (© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: Adipose-tissue derived adiponectin has gained a lot of interest as a marker of metabolic syndrome (MetS) and cardiovascular risk. The objective of this study was to assess whether adiponectin levels in young adults predict the incidence of MetS after 6-year follow-up. To gain insight on the interrelations between MetS, adiponectin and cardiovascular risk, we also examined the associations of adiponectin and carotid atherosclerosis according to MetS status., Methods: This analysis was part of a population-based, longitudinal cohort study conducted among 1693 Cardiovascular Risk in Young Finns Study individuals (age 31.9 ± 4.9 years in 2001) participating in follow-ups in 2001 and 2007., Results: In a multivariable model adjusted for age, sex, MetS components, LDL-cholesterol, CRP, insulin, leptin, smoking and family history of coronary disease, 1-unit increase in baseline adiponectin levels was associated with reduced odds (odds ratio [OR]=0.94, 95% CI 0.89-0.99, P=0.04) of incident MetS. Of the MetS components, adiponectin levels were inversely associated with the incidence of hyperglycemia in multivariable analyses (OR=0.94 (0.90-0.99), P=0.04). When studying the adiponectin×MetS interaction on IMT, we observed a significant interaction when examining IMT in 2001 (r=-0.11 (MetS(-)) vs. r=-0.17 (MetS(+)), P for interaction 0.047) and IMT in 2007 (r=-0.12 (MetS(-)) vs. r=-0.21 (MetS(+)), P for interaction 0.005), suggesting the inverse association between adiponectin and IMT is stronger among those with MetS., Conclusions: Among young adults, high adiponectin levels were associated with decreased incidence of MetS. Moreover, our data suggest that individuals with MetS are more vulnerable to the proatherogenic effects of low adiponectin levels., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aims: To evaluate whether good statin adherence is associated with a reduced incidence of major coronary events (MCEs) among diabetic patients with and without coronary heart disease (CHD)., Methods: Using data derived by linkage of nationwide health databases in Finland, we conducted a nested case-control analysis of 3513 cases with an MCE, a composite of acute myocardial infarction and/or coronary revascularization, and 20,090 matched controls identified from a cohort of 60,677 statin initiators with diabetes. Cases and controls were matched according to gender, time of cohort entry and duration of follow-up and further classified to two risk groups according to the presence of CHD at statin initiation. The incidence of MCEs was compared between patients with good statin adherence (the proportion of days covered ≥80%) and patients with poor statin adherence (<80%). Odds ratios (OR) for MCEs were estimated by conditional logistic regression adjusting for several covariables., Results: Good statin adherence was associated with a reduced incidence of MCEs in those with prior CHD [OR 0.84 (95% CI 0.74-0.95)] and in those without it [OR 0.86 (95% CI 0.78-0.95)]. The association persisted among those followed up for 5 years or longer [OR 0.77 (95% CI 0.58-1.02) and OR 0.79 (95% CI 0.66-0.94) respectively]. In sensitivity analyses, a reduced MCE incidence was observed also in those without any documented cardiovascular disease (CVD) at statin initiation [OR 0.87 (95% CI 0.78-0.96) overall and OR 0.80 (95% CI 0.66-0.97) for those followed up 5 years or longer]., Conclusions: In patients with diabetes, good adherence to statins predicts reduced incidence of MCEs irrespective of the presence of CHD at statin initiation., (© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.)

Background & Aims: Ectopic fat in muscle and liver is linked to obesity and type 2 diabetes. Recently, pancreatic lipid accumulation has also been associated with β-cell dysfunction and reduced insulin production, leading to the development of type 2 diabetes. Physical exercise training has been shown to attenuate β-cell dysfunction in patients, but little is known about its effects on pancreatic and hepatic fat accumulation. In this study, we validated in-vivo proton magnetic resonance spectroscopy ((1)H MRS) in pancreatic fat measurement with biochemical measurements in a pig model. Thereafter, the effects of increased physical activity on the amounts of pancreatic and liver fat were studied in eight monozygotic twin pairs who have discordant physical activity and fitness., Methods: Pancreatic fat content was studied in 15 pigs using (1)H MRS and/or biochemical analyses. In addition, liver and pancreatic fat were assessed using (1)H MRS in eight monozygotic male twin pairs with 18% mean difference in VO(2max) between the twin brothers., Results: Twins with higher physical fitness had 23% less liver fat (1.3±1.3% vs. 2.1±2.6%, p=0.022) but no such difference was observed in the pancreatic fat (8.2±9.3% vs. 9.8±8.5%, respectively, p=0.3). Hepatic fat content was inversely associated with VO(2max). A positive association was found between pancreatic and liver fat contents (β=5.18, p=0.012). Pancreatic fat content was also associated with insulin sensitivity indexes and plasma adiponectin and glutamyltransferase concentrations., Conclusions: Pancreatic fat content is associated with insulin resistance and hepatic fat content. An active lifestyle seems to beneficially influence hepatic fat metabolism., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)