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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: 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).)

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.)

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.

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.

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.

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.)

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.)

High drug consumption among the elderly and inappropriate prescribing practices increase the risk of adverse drug effects in this population. This risk may be decreased by conducting, for example, a medication review alone or as part of a comprehensive geriatric assessment (CGA); however, little is known about the fate of the changes in medication made as a result of the CGA or medication review. To study the performance of the CGA with regards to medication changes and to determine the persistence of these changes over a 1-year period. This study was a population-based intervention study. A random sample of 1000 elderly (age > or =75 years) was randomized either to a CGA group or to a control group. Home-dwelling patients from these groups (n = 331 and n = 313 for intervention and control groups, respectively) were analysed in this study. Study nurses collected information on medication at study entry and 1 year later in both groups; in the intervention group, study physicians assessed, and changed when appropriate, the medication at study entry. The medication changes and their persistence over 1 year were then evaluated. Medication changes were more frequent in the intervention group than in the control group. Regular medication was changed during follow-up in 277 (83.7%) and in 228 (72.8%) [odds ratio (OR) 1.9; 95% CI 1.3, 2.8] patients in the intervention and control groups, respectively. In the intervention group, study physicians were responsible for 35.4% of all new prescriptions and for 15.6% of all drug terminations. Changes took place particularly in the prescription of CNS drugs. About 58% of the drugs initiated by study physicians were still in use 1 year later, and 25.5% of those terminated by study physicians had been reintroduced. Drug intervention as part of a CGA can be used to rationalize the drug therapy of a patient. However, its effectiveness is subsequently partly counteracted by other physicians working in the healthcare system.

Objective: To analyze differences in the pattern of statin use among 10 consecutive yearly cohorts of new users in Finland., Study Design: Retrospective cohort study based on administrative claims data., Methods: New users of statins from January 1, 1995, to December 31, 2004, were captured from a nationwide prescription register, and the pattern of statin use was observed until December 31, 2005. The association between year of statin initiation and persistence with statin therapy during the first year of statin use was modeled using Cox proportional hazards regression analysis with multivariable adjustment. The median adherence (proportion of days covered) was computed among patients who discontinued therapy during each 365-day interval since statin initiation., Results: In total, 490,024 new users of statins were identified. In the multivariable-adjusted model, discontinuation during the first year among initiators of statin use in 1996 and 1997 was similar to that in 1995 (hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.95-1.03 in 1996; and HR, 1.01; 95% CI, 0.98-1.05 in 1997). Compared with the 1995 cohort, the 1998, 1999, 2000, 2001, 2002, 2003, and 2004 cohorts were less likely to discontinue statin use. Hazard ratios of discontinuation for the cohorts ranged from 0.91 (95% CI, 0.88-0.94) in 1998 to 0.80 (95% CI, 0.78-0.83) in 2004. There were no differences in adherence with respect to the duration of therapy among the yearly cohorts., Conclusions: Compared with the 1995 cohort, 1-year persistence with statin therapy in Finland improved among new users of statins in 1998, and the improvement persisted up to 2004. Adherence to statin therapy remained stable among initiators from 1995 to 2004.

Background: The prevalence of asthma and obesity is increasing concomitantly, but many aspects of this link are unclear. Our objective was to examine whether obesity is associated with asthma in three time points of life, and whether immunomodulatory adipokines, leptin and adiponectin are linked to overweight-associated asthma., Methods: We studied the association between obesity and asthma at ages 3-18 years [mean (SD), 10 years (5), n = 3582, year 1980], 9-24 years [16 years (5), n = 2764, 1986] and 24-39 years [32 years (5), n = 2620, 2001] in a prospective cohort study and further tested for associations with serum leptin and adiponectin concentrations. Data on allergy status, smoking and other laboratory values (serum insulin, plasma C-reactive protein and serum lipid values) were also analyzed., Results: Allergy and parental asthma were significantly associated with asthma at all ages. At ages 24-39 years, but not earlier, body mass index (BMI) (odds ratio, OR 1.05; P = 0.019) and female gender (OR 1.56; P = 0.031) were independently associated with asthma. Increase in BMI was also associated with incident asthma during adulthood (OR 1.08; P = 0.030). Levels of leptin, adiponectin or any other obesity-related biomarker were not independently associated with asthma., Conclusions: Asthma is linked with obesity in adults, but our results do not support a significant role for leptin, adiponectin or any other obesity-related biomarker studied in this association. Other factors should be sought for better understanding the connection between obesity and asthma.

Persistence with statin therapy was studied among 562 598 new statin users in 1995-2005 in Finland. Discontinuation was most likely during the first year. Persons with diabetes (15.0% of initiators) were significantly more likely to continue statin therapy compared with person not having diabetes.

Background: Use of combined oral contraceptives (COCs) is known to increase concentrations of C-reactive protein (CRP), an important predictor of cardiovascular disease. The inflammatory nature of the disease is well acknowledged. The aim of this study was to find out whether the metabolic, lifestyle and genetic determinants of CRP differ between women who use COCs and those who do not use any hormonal contraceptives (non-users)., Material and Methods: A total of 1,257 women (24-39 years) participated in the ongoing Cardiovascular Risk in Young Finns Study, a population based cross-sectional follow-up study. Use of hormonal contraceptives was determined by questionnaire. Plasma CRP and other cardiovascular risk factors were measured; five CRP gene polymorphisms were genotyped (-717A>G, -286C>T>A, +1059G>C, +1444C>T and +1846G>A) and CRP haplotypes were constructed., Results: Multivariate regression analysis revealed that BMI and leptin were the main determinants of CRP in non-users, whereas in COC users the main determinants were BMI, leptin and triglycerides. The median CRP and triglyceride values were significantly higher in COC users than in non-users. The correlations between triglyceride and CRP were tested separately in different COC users in accordance with progestagen content and dosage, the analysis revealing significant association only in women using a high dosage of progestagen or cyproterone. The haplotypes of CRP gene had no significant association with CRP concentration in COC users, while independent effects on CRP were found in non-users., Conclusion: Our study suggests that use of COCs alters the metabolic determinants and genetic regulation of CRP.

Aim: To describe nation-wide secular trends in statin use., Methods: Reimbursed prescriptions for lipid lowering drugs between 1995 and 2005 in Finland were retrieved from the nation-wide Prescription Register. The 1 year prevalence and incidence of statin use stratified by gender and age of users were measured for each calendar year. The relative changes (RR) in the incidence and the prevalence were calculated by using the year 1995 as a reference., Results: The 1 year prevalence increased 11-fold (95% confidence interval 11.2, 11.5), i.e. from 7.8 per 1000 inhabitants in 1995 to 88.9 in 2005. The incidence increased five-fold (95% CI 4.9, 5.1) from 355 per 100 000 inhabitants to 1772 during the respective years. The prevalence and incidence were the highest among persons aged 65-74 years. The largest relative increase in incidence was found among those aged >/= 75 years, in both females (RR 14.1, 95% CI 13.0, 15.3) and males (RR 14.0, 95% CI 12.5, 15.7). Since 2002 the prevalence has been higher among females (P < 0.05)., Conclusions: As statin use has increased particularly among the elderly, further studies on the benefits in real life situation are needed in this age group.

Both low back pain (LBP) and obesity are common public health problems, yet their relation remains controversial. The aim of this study was to investigate the associations between weight-related factors and the prevalence of LBP in young adults in Finland. Participants in the ongoing Cardiovascular Risk in Young Finns Study aged 24-39 years were included (N = 2,575). In 2001, 31.2% of men and 39.5% of women reported LBP with recovery within a month or recurrent or continuous pain during the preceding 12 months. For women only, those with higher body mass index, waist circumference, hip circumference, waist-to-hip ratio, serum leptin level, and C-reactive protein level showed an increased prevalence of LBP. With all weight-related factors in the model, only waist circumference was related to LBP in women. For women, the odds ratios of LBP were 1.2 (95% confidence interval: 0.8, 1.8) for a waist circumference of 80-87.9 cm and 1.8 (95% confidence interval: 1.0, 3.2) for a waist circumference of > or =88 cm compared with a waist circumference of <80 cm. This association was independent of C-reactive protein, leptin, and adiponectin levels. The authors' findings in a relatively young population suggest that abdominal obesity may increase the risk of LBP in women.

Background: Preventive statin therapy is often recommended as lifelong treatment., Objective: The aim of this study was to analyze persistence with statin therapy over a decade of use and to identify factors associated with its discontinuation., Methods: Persistence with therapy among new users of statins in 1995 was followed up until December 31, 2005, in Finland using the nationwide drug reimbursement register. Cumulative persistence was analyzed using Kaplan-Meier analysis. A Cox regression model was applied to analyze associations of various baseline covariates with discontinuation. We further modeled the association of time-specific covariates by stratifying the duration of therapy in years and using a logistic regression in which those continuing therapy until the end of follow-up (persistent users) formed the reference group. Adherence, defined as the proportion of days covered by statins, stratified by the timing of discontinuation, was computed for the respective groups., Results: Of the 18,072 new statin users, 73.3% (n =13,254) were aged >54 years and 54.8% (n =9908) were men. Of this cohort, 43.9% (n = 7926) were using statins throughout and at the end of the tenth year. Sex was not associated with persistence at any point. In the Cox model, persons aged 45 to 74 years at initiation were more likely to continue statin use than younger or older age groups. Among those who still used statins after the fifth year of observation, the age difference was not observed in the logistic regression model. The use of 1, 2, 3, or > or =4 cardiovascular drugs before the initiation predicted continuation relative to no cardiovascular drug use (hazard ratio for discontinuation significantly <1.00 in all comparisons). Adherence was best (median 93.9%) among the persistent users., Conclusions: The 10-year persistence with statin use in this general population was approximately 44%. Persons aged 45 to 74 years at initiation and those with at least 1 prescription for another cardiovascular medication were the most likely to continue statin therapy up to the fifth year.

Objective: The trend towards polypharmacy is increasing among the elderly, and associated with this trend is an increased risk of adverse drug effects and drug-drug interactions. Our objective was to assess whether drug adverse effects reported by patients are in general agreement with those identified by a physician., Methods: We evaluated the medication of 404 randomly selected individuals aged 75 years or older by means of interviews carried out by trained nurses and examinations conducted by a physician. The medication used by these patients was recorded prior to the physician's examination and modified thereafter if considered appropriate. Adverse effects noted by the physician were compared to those self-reported by the patients., Results: Almost all of the patients (98.8%) were using at least one drug, and the mean total number of drugs used was 6.5. Adverse effects were self-reported by 11.4% of the patients, whereas the physician observed apparent adverse drug effects in 24.0% of the patients. No adverse effects were reported in 53.2% of the patients. There were only seven patients that had adverse effects that were both self-reported and identified by the physician, and only four of these patients reported the same adverse effect that had been identified by the physician., Conclusion: There was a great disparity between the adverse effects identified by the physician and those reported by the patients themselves. Based on our results, it would appear that elderly people tend to neglect adverse drug effects and may consider them to be an unavoidable part of normal ageing. Therefore, physicians should enquire about possible adverse effects even though elderly patients may not complain of any drug-related problems.

Objectives: To study the risk of serious upper gastrointestinal (GI) events associated with the concurrent use of selective serotonin re-uptake inhibitors (SSRIs) and different types of non-steroidal anti-inflammatory drugs (NSAIDs)., Methods: This was a nationwide, register-based matched case-control study on non-institutionalized residents of Finland during the period 2000-2004. Patient-cases with serious upper GI events (n=9191) were drawn from the Hospital Discharge Register, and individually matched controls (n=41,780) were drawn from the Population Register. Logistic regression was applied in the data analysis, and adjustments were made for various co-morbidities and the use of other drugs associated with the risk of serious upper GI event., Results: The adjusted odds ratio (AOR) of serious upper GI events for SSRI use compared to non-use of SSRIs or NSAIDs was 1.30 [95% confidence interval (95%CI: 1.13-1.50)], and the AOR for concurrent SSRI and NSAID use compared to the non-use of either drug was 4.19 (95%CI: 3.30-5.31). The AOR of upper GI events for the concurrent use of SSRIs with NSAIDs compared to patients using NSAIDs only was 1.57 (95%CI: 1.24-1.99). The respective AOR for traditional, non-selective NSAIDs was 1.77 (95%CI: 1.31-2.38), for semi-selective NSAIDs (nimesulide, nabumetone, meloxicam, and etodolac) 1.30 (95%CI: 0.76-2.24) and for COX-2 selective NSAIDs 1.33 (95%CI: 0.70-2.50)., Conclusions: The concurrent use of SSRIs and NSAIDs is associated with a moderate excess relative risk of a serious upper GI event when compared with NSAID use alone.

Aims: To evaluate the risk of first myocardial infarction (MI) associated with the use of various non-steroidal anti-inflammatory drugs (NSAIDs) in the general population., Methods and Results: We conducted a population-based matched case-control study over the years 2000-3 in outpatient residents of Finland. In the nationwide Hospital Discharge Register 33 309 persons with first time MI were identified. A total of 138 949 controls individually matched for age, gender, hospital catchment area, and index day were selected from the Population Register. For combined NSAIDs, the adjusted odds ratio for the risk of first MI with current use was 1.40 (95% CI, 1.33-1.48). The risk was similar for conventional (1.34; 1.26-1.43), semi-selective (etodolac, nabumetone, nimesulide, and meloxicam) (1.50; 1.32-1.71), and cyclo-oxygenase-2 (COX-2) selective NSAIDs (rofecoxib, celecoxib, valdecoxib, and etoricoxib) (1.31; 1.13-1.50). Age of current user did not consistently modify the risk. No NSAID was associated with an MI-protective effect. All durations from 1 to 180 days of conventional NSAIDs and from 31 to 90 days duration of COX-2 selective NSAIDs were associated with an elevated risk of MI., Conclusion: Current use of all NSAIDs is associated with a modest risk of first time MI.

Objective: A number of drugs used concurrently with non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of gastrointestinal (GI) haemorrhage. We studied the prescribing of NSAIDs with corticosteroids, oral anticoagulants or selective serotonin re-uptake inhibitors (SSRIs), as well as the use of gastroprotection among continuous and non-continuous users of NSAIDs in Finland., Methods: Concurrent use of various drugs was analysed in a nested case-control study in a population-based cohort of NSAID users in 2000 using data in the National Prescription Database., Results: Prescribing of any other drug with the potential to increase the risk of GI bleeding with NSAIDs was five times [5.2; 95% confidence interval (CI) 4.7-5.9] more common among continuous than non-continuous NSAID users, and the odds ratio for oral corticosteroids was 8.0 (95% CI 6.6-9.6). Of patients using continuous NSAIDs with oral corticosteroids, 73.3% had rheumatoid arthritis (RA). After excluding RA patients, the odds ratio remained high (4.5; 95% CI 3.3-6.1) and at the same level as for SSRIs (3.7; 3.1-4.4). Gastroprotective drugs were prescribed for 6.8% of the continuous users of NSAIDs alone, and for 20.4% of patients taking any of the studied drug combinations with NSAIDs. The continuous users of NSAIDs alone had gastroprotection 2.9 (2.5-3.3) times more often than other users of NSAIDs. With drug combinations (NSAID+corticosteroid, NSAID+SSRI, NSAID+anticoagulants), the use of gastroprotection did not differ from patients using lower amounts of NSAIDs., Conclusions: When prescribing NSAIDs, situations leading to habitual use should be avoided, potential complications due to clustering of risk factors recognised, and gastroprotection prescribed for patients with increased risk of GI haemorrhage.

Most western societies are enhancing rational pharmacotherapy to get best value for the constantly increasing expenditure on drugs. Government bodies and the medical profession took joint responsibility for the education programme for rational prescribing, launched in Finland at the end of the 1990s. The goals were to enhance critical thinking, and when appropriate, change prescribing behaviour. Various approaches that included evidence-based continuing medical education (CME), implementing clinical guidelines, delivering information, and providing prescribing feedback were used simultaneously. The commitment of the stakeholders and participants has been strong and the approaches have succeeded even though there is no clear outcome measure. The Government has recently decided to continue and widen the process, which started as a pilot programme, on a tight budget.

Objective: To describe characteristics of non-steroidal anti-inflammatory drugs (NSAIDs; Anatomical Therapeutic Chemical code M01A) users in Finland, with emphasis on intensity of use., Methods: Nationwide prescription database study over years 1997-2000 using a random sample of 500,000 persons. Low use was defined as 30 or fewer defined daily doses (DDDs) per year, moderate between 31 and 181 DDDs, and heavy 182 or more DDDs. Persons with rheumatoid arthritis (RA) were identified and analysed separately from non-RA patients., Results: The total NSAID consumption was 61.2 and reimbursed prescription NSAID use 31.2 DDD/1000 inhabitants per day in 2000. The annual prevalence of use varied between 17.1% and 18.8% throughout 1997-2000, and that of low, moderate and heavy use was 7.6%, 8.0% and 1.5%, respectively, in 2000. Females used more NSAIDs than men in all adult non-RA age groups, and of non-RA patients 58.4% were females. The share of females among the non-RA users increased with the intensity of use, as did the share of female patients 65 years or older. Among RA patients, the intensity of use was independent of age and gender, and 70% of RA patients were females. Of the heavy users in 2000, 27.7% ( n=2117) had continuously used 182 or more DDDs per year throughout the years 1997-2000. Non-RA users accounted for 78.4% of the annual heavy and 64.2% of the continuous heavy users., Conclusions: Exposure of patients to long-term use of NSAIDs and upper gastrointestinal bleeding should be reduced by regular analysis of patient's pain and consideration of other treatment options.

Plasma kinetics and beta-receptor blocking and -binding activity of timolol was studied in six healthy volunteers following its intravenous 0.25 mg dose. Timolol concentrations were measured using radioreceptor assay (RRA), blocking activity by comparing the dose ratios (DRs) of the infusion rates of isoprenaline required to increase heart rate by 25 bpm (I25) and binding activity by determining the extent to which timolol occupied beta 1-receptors of rabbit lung and beta 2-receptors of rat reticulocytes in undiluted plasma samples. Timolol was eliminated from plasma with a mean half-life for the elimination phase of 2.6 hours. The dose antagonized potently isoprenaline-induced tachycardia at least for four hours. The effect was excellently correlated with the estimated beta 2-receptor binding activity of timolol in the circulating plasma. In conclusion, the small intravenous timolol dose was eliminated from plasma by a fashion, which was very similar to its eighty-fold higher oral doses reported earlier in the literature. The 0.25 mg dose was of considerable systemic beta-receptor blocking and -binding activity, that may help to explain its reported side-effects following ocular drug administration. The extent to which beta-blocking agents occupy rabbit lung beta 1- and rat reticulocyte beta 2-receptors in the circulation appears to predict the intensity and selectivity of their beta-blocking effects in healthy volunteers.

1. The debrisoquine hydroxylation phenotype was assessed in 211 healthy subjects of Finnish Caucasian origin. 2. A bimodal distribution was observed in the urinary debrisoquine/4-hydroxydebrisoquin ratio. Eleven subjects (about 5%) were poor metabolizers of debrisoquine, when a ratio of 12.6 was used as the cut-off point. 3. The mean metabolic ratio of 35 extensive metabolizers taking oral contraceptives was slightly lower than that of extensive metabolizers not taking contraceptives. This indicates that oral contraceptives may change the phenotyping near the metabolic ratio of 12.6. 4. The metabolic ratios were determined in eight subjects using both 4 h and 6 h urine collection times. The metabolic ratios corresponded well with each other indicating the usefulness of the shorter 4 h collection time.