Clinical trial site identification practices and the use of electronic health records in feasibility evaluations: An interview study in the Nordic countries.

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.

Adherence to statin therapy and the incidence of ischemic stroke in patients with diabetes.

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.

Impact of Statin Adherence on Cardiovascular Morbidity and All-Cause Mortality in the Primary Prevention of Cardiovascular Disease: A Population-Based Cohort Study in Finland.

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.

Analgesic use before and after oral anticoagulant initiation--a population-based study in Finland.

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.

Factors associated with nursing students' medication competence at the beginning and end of their education.

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.

Lifestyle factors as predictors of nonadherence to statin therapy among patients with and without cardiovascular comorbidities.

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.

Older statin initiators in Finland - cardiovascular risk profiles and persistence of use.

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 education in nursing programmes in Finland--findings from a national survey.

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.

Prescribing Appropriate Medicines to Older Adults: A Finnish Experience with the Web-Based Meds75+ Database.

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.

Influence of retirement on nonadherence to medication for hypertension and diabetes.

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.

Statin use among older Finns stratified according to cardiovascular risk.

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.

Comprehensive geriatric assessment decreases prevalence of orthostatic hypotension in older persons.

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.

Reimbursement and use of oral anticoagulants during 2014-2022 - A register-based study.

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.

Success and failure factors of patient recruitment for industry-sponsored clinical trials and the role of the electronic health records-a qualitative interview study in the Nordic countries.

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.

Liver and pancreatic fat content and metabolism in healthy monozygotic twins with discordant physical activity.

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 ß-cell dysfunction and reduced insulin production, leading to the development of type 2 diabetes. Physical exercise training has been shown to attenuate ß-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 (ß=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.

Heart rate variability is independently associated with C-reactive protein but not with Serum amyloid A. The Cardiovascular Risk in Young Finns Study.

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.

Statin adherence and the risk of major coronary events in patients with diabetes: a nested case-control study.

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.

Dynamics of long-term statin therapy.

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.

Assessing an Electronic Health Record research platform for identification of clinical trial participants.

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.

First insight to the Finnish nationwide electronic prescription database as a data source for pharmacoepidemiology research.

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.