Finnish Prescription Register Research Articles

Symptomatic and Preventive Medication Use before and after Alzheimer's Disease Diagnosis: A 10-Year Matched Cohort Study

ObjectiveTo investigate longitudinal changes in symptomatic and preventive medication use among community-dwelling people with and without Alzheimer's disease (AD) 5 years pre- and post-AD diagnosis. DesignRetrospective matched cohort study. Settings and ParticipantsThe sample comprised 58,496 people with a geriatrician/neurologist-verified AD diagnosis matched 1:1 for age, sex, and region to people without AD in Finland. MethodsMedication dispensing data were obtained from the Finnish Prescription Register. Prevalence of symptomatic and preventive medication use was evaluated every 6 months from 5 years pre- to post-AD diagnosis. Longitudinal changes in medication use between people with and without AD were compared using ordinal logistic regression. ResultsDuring the 5 years pre- and post-diagnosis, there were differences in symptomatic (P < .001) and preventive (P = .006) medication use between people with and without AD. Over the 5 years pre-diagnosis, prevalence of symptomatic and preventive medications increased in both people with and without AD. During the 1 year pre-diagnosis, people with AD had a higher increase in use of ≥3 symptomatic medications (+4.4% vs +2.2%) and ≥3 preventive medications (+6.4% vs +2.9%) compared to people without AD. Over the 5 years post-diagnosis, symptomatic medication use plateaued in both people with and without AD. Meanwhile, people using ≥3 preventive medications decreased (−6.0%) in those with AD, but increased (+6.1%) in those without AD. During the follow-up period, people with AD had a larger absolute percentage increase in prevalence of antipsychotics (+22.7% vs +1.8%) and antidepressants (+19.1% vs +5.0%) than people without AD. During the same period, paracetamol and calcium supplement use increased by 31.1% and 20.4%, respectively, among people with AD. The largest absolute percentage decrease in prevalence of preventive medications over the 5 years post-diagnosis were beta-blockers (−9.8%) and statins (−7.0%) in people with AD. Conclusions and ImplicationsAt the point of and following diagnosis, there were population-level changes in medication use among people with AD. Medication assessments during this period appear to coincide with discontinuation of preventive medications whereas minimal changes were observed in symptomatic medication use.

Trends in the use of psychotropics in older people with dementia: interrupted time series of Finnish clinical guidelines of behavioural and psychological symptoms of dementia.

Up to 90% of people with dementia experience behavioural and psychological symptoms of dementia (BPSD) as part of their illness. Psychotropics are not recommended as the first-line treatment of BPSD because older people are more prone to adverse reactions. In this study, we evaluate the impact of the Finnish clinical guidelines of BPSD (published in 2017) on psychotropic use in people with dementia. This study is based on Finnish Prescription Register data from 2009 to 2020. The data included all community-dwelling Finnish people aged ≥65 and who had anti-dementia medication purchases (n= 217,778). We used three-phased interrupted time series design to evaluate the changes in levels and trends of monthly (n= 144) psychotropic user rates compared with the predicted trends. In addition, we evaluated the changes in levels and trends of monthly new psychotropic user rates. The level of monthly psychotropic user rate decreased non-significantly during the intervention period (β -0.057, P= 0.853), and during the post-intervention period, there was an increase in the level (β 0.443, P= 0.091) and slope (β 0.199, P= 0.198), but not statistically significant. The level of monthly new psychotropic user rate (β -0.009, P= 0.949) during the intervention period and the level (β 0.044, P= 0.714) and slope (β 0.021, P= 0.705) during the post-intervention period were almost unchanged. Results may indicate possible challenges in deprescribing and better adherence to the guidelines at the beginning of BPSD treatment. Further research into the barriers to implement BPSD guidelines and the availability of non-pharmacological treatments is needed.

Regional variation in potentially inappropriate medicine use in older adults. - A national register-based cross-sectional study on economic, health system-related and patient-related characteristics.

Potentially inappropriate medicines (PIM), i.e. medicines in which the potential harms may outweigh the benefits, use may be associated with e.g. hospitalization, outpatient visits and health care costs. As regional institutions are often responsible for financing pharmaceuticals, understanding the regional variation of PIM use could help to tackle the associated problems and costs. To explore regional variation in PIM use among older adults and the association with regional health-system related, patient-related and economic characteristics and the frequency of PIM use. This is a nation-wide study based on the Finnish Prescription Register. PIM use was defined according to the Finnish Meds75+ database and regional characteristics derived from national statistics. Variation at the hospital district level was large, with the largest difference between the most and least PIM prescribing being 45.2%. The factors associated with high PIM prescribing were a higher share of women and a higher number of private doctor visits per inhabitant in a municipality. The factor associated to lower PIM prescribing was a higher share of Swedish-speaking population. The studied factors explained 23% of the municipal-level variation in PIM. Large regional differences may lead to regional inequality in prescribing and in the distribution of pharmaceutical costs. As only a small share of the variation was explained by economic, health system-related and patient-related factors, the key reasons may lie in unobserved prescribing practices.

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

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. 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. All prescriptions, dispensations, and their cancellations and corrections for OACs recorded in Kanta were retrieved for the period 2012-2016. 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. 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.

Patient- and health care-related factors associated with initiation of potentially inappropriate medication in community-dwelling older persons.

Potentially inappropriate medications (PIMs) in older persons are defined as medications of which the potential harms outweigh their benefits. The purpose of this study was to determine how initiation of PIMs accumulate in community-dwelling persons aged 65-74 and ≥75years, and which patient- and health care-related factors are associated with PIM initiation over time. Data of this study were gathered from population-based registers by a 10% random sample of persons (n=28497) aged ≥65years with no prior PIMs within a 2-year period preceding the index date (1 January 2002), and the study individuals were followed until 2013. The Finnish Prescription Register was linked using a personal identity code to register on inpatient care and causes of deaths and socio-economic data. In this study, 10698 (37.5%) persons initiated PIMs during the study period. Female gender was associated with PIM initiation in 65-74-year-olds, but not in ≥75-year-olds. In 65-74-year-olds, the risk of PIM initiation increased with the higher income, whereas in ≥75-year-olds, the association between PIM initiation and the high income was not significant. The prescribing physician explained 9%-16% of the variation in the probability of PIM initiation. In conclusion, there were age-related differences in the factors associated with PIM initiation in relation to gender and socio-economic status. Overall, patient-related factors explained a large proportion of variation of PIM initiation, but there were also differences in PIM prescribing among physicians. However, physician-related variance of PIM initiations decreased during the 12-year follow-up.

The association of potentially inappropriate medication use on health outcomes and hospital costs in community-dwelling older persons: a longitudinal 12-year study.

To determine (1) whether potentially inappropriate medication (PIM) use defined by the Meds75 + database is associated with fracture-specific hospitalisations and all-cause mortality, and (2) the association between PIM use and all-cause hospitalisation costs in a 12-year follow-up of a nationwide sample of people aged ≥ 65years in Finland. This is a longitudinal study of 20,666 community-dwelling older persons with no prior purchases of PIMs within a 2-year period preceding the index date (1 Jan 2002), who were followed until the end of 2013. Data were obtained from the Finnish Prescription Register, and it was accompanied by information on inpatient care, causes of deaths and socioeconomic status from other national registers. Propensity score matching (PSM) analysis was used to account for potential selection effect in PIM use. Cox proportional hazards regression was used to identify the time to the first fracture or death by comparing PIM-users (n = 10,333) with non-users (n = 10,333). The association between PIM use and hospital costs was analysed with a fixed effects linear model. PIM use was weakly associated with an increased risk of fractures and death. The association was stronger in the first PIM-use periods. Hospitalised PIM-users had 15% higher hospital costs compared to non-users during the 12-year follow-up. PIM initiation was associated with an increased risk of fracture-specific hospitalisation and mortality and PIM-users had higher hospital costs than non-users. Health care providers should carefully consider these issues when prescribing PIM for older persons.

Trends in the long-term use of benzodiazepine anxiolytics and hypnotics: A national register study for 2006 to 2014.

Long-term benzodiazepine (BZD) treatment continues to be a debated topic. Because individual BZDs have different clinical profiles, we assessed the nationwide trends of long-term BZD use at active substance level during years 2006 to 2014. This study covered all reimbursed BZD purchases (n=408572-521823 annually) for adults recorded in the Finnish Prescription Register. We assessed long-term use (annual cumulative purchase of ≥180 defined daily doses) in general, and at active substance level with the most commonly used BZD anxiolytics (oxazepam, diazepam, alprazolam, and clonazepam for nonepilepsy indications) and hypnotics (zopiclone, zolpidem, and temazepam) included. The persistence rates for each substance were assessed separately. The prevalence of long-term BZD use among Finnish adults declined significantly from 5.3% to 3.6%, during years 2006 to 2014. Despite this decline, there was a significant increase in the long-term use of clonazepam for nonepilepsy indications and zolpidem (28.0% and 17.5%, respectively). Long-term use was common in the aged population, as well as among the users of hypnotics or clonazepam. Persistent use of 9 consecutive calendar years varied between 7.5% for incident alprazolam users and 21.0% for incident clonazepam users. We found a declining trend in long-term BZD use, but the decline was not uniform between the substances-the long-term use of clonazepam and zolpidem even increased. Follow-up research is needed to assess whether the decline in BZD use is accompanied by an increased use of other types of anxiolytic or hypnotic drugs or other forms of treatment.

Decreasing Trend in the Use and Long-Term Use of Benzodiazepines Among Young Adults.

Patterns of benzodiazepine (BZD) use and long-term use among young adults are not well known. Our aim was to study trends in BZD use and long-term use among 18-25-year-old young adults by gender and active substance in a nationwide retrospective longitudinal register-based setting. All Finns aged 18-25 years with reimbursed purchases of BZDs in 2006-2014 recorded to the Finnish Prescription Register were included. Annual prevalence rates of BZD use and long-term use among young adults were reported overall, according to gender, drug group (anxiolytic or hypnotic), and active substance. Long-term use of BZDs was defined as purchasing ≥180 Defined Daily Doses (DDDs) in at least two drug purchases during a calendar year. Overall prevalence of BZD use among young adults decreased from 24.0 to 18.8 users per 1000 inhabitants in 2006-2014. Prevalence of long-term use decreased from 5.5 to 3.3 users per 1000 inhabitants. Overall BZD use was higher among females, whereas long-term use was more common among males. Use of anxiolytics was more common than use of hypnotics. Oxazepam, alprazolam, zopiclone, and zolpidem were the most used BZDs, whereas alprazolam and clonazepam were the substances with most long-term use. The use and long-term use of BZDs have decreased annually since 2008 among Finnish young adults. Further research is needed to investigate the reasons behind the decline.

Diabetes and risk of occupational injury: a cohort study.

To investigate if diabetes is associated with a higher risk of occupational (workplace or commuting) injury. Medication data from the Finnish Prescription Register were used to identify diabetes cases in 2004 in a large employee cohort (the Finnish Public Sector study). These data were linked to injury records obtained from the Federation of Accident Insurance Institutions. A total of 1020 diabetes cases (median age 52 years, range 20 to 65 years; 66% women) and their 5234 age- and sex-matched controls were followed up until 2011. Sex-stratified Cox proportional hazards models, adjusting for age, occupational status, obesity and health behaviours, were applied. Because of the small number of men in the cohort, injury types and locations were only examined among women. During the median follow-up of 6.7 years, 25% of the participants with diabetes (n=252) and 20% of those without (n=1051) experienced an occupational injury. The association between diabetes and injury was stronger in women than men (P=0.048). Diabetes was associated with a higher risk of workplace (hazard ratio 1.37, 95% CI 1.11 to 1.69) and commuting (hazard ratio 1.36, 95% CI 1.03 to 1.79) injury in women. With regard to different injury types and locations, diabetes was associated with bone fractures, dislocations, sprains and strains, and injuries to upper and lower extremities. In men, there was an association between insulin-treated diabetes and commuting injury (hazard ratio 3.14, 95% CI 1.52 to 6.49). Diabetes was associated with workplace and commuting injuries in women. Men with insulin-treated diabetes had a higher risk of commuting injuries.

Long-term use of antipsychotics among community-dwelling persons with Alzheimer׳s disease: A nationwide register-based study

Antipsychotics are recommended only for short-term treatment of severe behavioral and psychological symptoms of dementia. Our objective was to study the duration of antipsychotic use and factors associated with long-term use (365 days or over) among community-dwelling persons with Alzheimer׳s disease (AD) during a 7-year follow-up. This was a nationwide register-based cohort study including all community-dwelling residents in Finland diagnosed with AD in 2005 (n=7217). The follow-up for antipsychotic use started 3 years before the diagnosis of AD and we applied a 7-year washout period to ascertain truly incident antipsychotic use. Follow-up ended on institutionalization, death or at the end of study period (December 31, 2009). Duration of antipsychotic use was modeled from individual purchase histories recorded in the Finnish Prescription Register. During the 7-year follow-up, 34% (2287/6740) of persons initiated antipsychotic use. Median duration of the first antipsychotic use period was 219 (interquartile range 85–583) days. Of those who discontinued antipsychotic use (n=1303), 44% restarted use later. Among users with at least one year of follow-up time after initiating antipsychotic use, prevalence of long-term use was 57% (893/1563). Long-term use was associated with initiation of use after AD diagnosis and choice of antipsychotic. Duration of use was more likely to be shorter among haloperidol users and longer among quetiapine users compared with risperidone users. In conclusion, long-term use of antipsychotics is frequent among community-dwelling persons with AD. Duration of use is not in line with the guidelines recommending time-limited use of antipsychotics.

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

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. 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). 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). 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.

From prescription drug purchases to drug use periods – a second generation method (PRE2DUP).

BackgroundDatabases of prescription drug purchases are now widely used in pharmacoepidemiologic studies. Several methods have been used to generate drug use periods from drug purchases to investigate various aspects; e.g., to study associations between exposure and outcome. Typically, such methods have been fairly simplistic, with fixed assumptions of drug use pattern and or dose (for example, the assumed usage of 1 tablet per day). This paper describes a novel PRE2DUP method that constructs drug use periods from purchase histories, and verified by a validation based on an expert evaluation of the drug use periods generated by the method.MethodsThe PRE2DUP method is a novel approach based on mathematical modelling of personal drug purchasing behaviors. The method uses a decision procedure that includes each person’s purchase history for each ATC code, processed in a chronological order. The method constructs exposure time periods and estimates the dose used during the period by considering the purchased amount in Defined Daily Doses (DDDs), which is recorded in the prescription register database. This method takes account of stockpiling of drugs, personal purchasing pattern; i.e., regularity of the purchases, and periods of hospital or nursing home care where drug use is not recorded in the prescription register. The method can be applied to a variety of drug classes with different doses and use patterns by controlling restriction parameters for each ATC class, or even each drug package. In the presented example, the PRE2DUP method was applied to a register-based MEDALZ-2005 study cohort. All drug purchases (3,793,085) recorded in the Finnish prescription register between 2002 and 2009 for persons with Alzheimer’s disease (28,093) were included.ResultsResults of the expert-opinion based validation indicate that PRE2DUP method creates drug use periods with a relatively high correctness. Drugs with varying patterns of use and drugs used on a short-term basis only require more precise parameters.ConclusionsPRE2DUP method gives highly accurate drug use periods for most drug classes, especially those meant for long-term use.

Cost-effectiveness of statin treatment for primary prevention in conditions of real-world adherence – Estimates from the Finnish prescription register

ObjectiveTo estimate the cost-effectiveness of statin therapy for primary prevention of coronary heart disease (CHD) events under real-world adherence. MethodsA 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. ResultsAt 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%. ConclusionsEven 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.

Register-based predictors of adherence among new statin users in Finland

Although register-based studies on statin adherence are increasing, for administrative data, little is known about the explanatory power of the predictors that explain adherence. The aim was to explore the ability of variables in administrative data to predict statin adherence in an unselected, universally insured population and, especially, to explore dispensation delay (time elapsed between prescription and dispensation) and out-of-pocket costs as explanatory factors. Statin initiators who were aged 45 to 75 years in 2000-2004 (n = 247, 051) were identified in the Finnish Prescription Register. First-year statin adherence was measured as the proportion of days covered (PDC). The effect of variables related to patient, health care, and payment was assessed with multivariable logistic regression. The C statistic was used to evaluate the explanatory power of different models. Overall, 54.6% of the cohort had good adherence (PDC ≥ 80%). The explanatory power of all the models was low (C = 0.666 for the full model). The multivariable models, including only payment variables, had a greater explanatory power (C = 0.627) than models with only patient (C = 0.602) or health care (C = 0.548) variables. A shorter dispensation delay and lower out-of-pocket costs predicted better adherence. Of other patient-related variables, age, presence of acute coronary syndrome, and use of cardiovascular medications were significant predictors of adherence. Type of statin and the prescriber's workplace were also significantly associated with adherence. Models based on administrative data do not provide useful prediction of statin adherence. Of the individual predictors, long dispensation delay may serve as a practical tool for identifying patients at risk of poor adherence. Increases in out-of-pocket costs predict nonadherence.

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

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

Evolution of paediatric off-label use after new significant medicines become available for adults: a study on triptans in Finnish children 1994-2007.

• Off-label use in children is widespread. New medicines lack marketing authorization for paediatric use, even when they represent significant therapeutic advantages and are intended for treatment of conditions common in children. • Until now no information exists on how off-label use in children develops over time after a significant new medicine is approved for adults and what happens when it is later labelled for one paediatric age group. • Off-label use of a new significant medicine begins in adolescents and extends to younger children with delay. First marketing authorization to adolescents, providing a more child-friendly formulation, results in increase of off-label use in younger children, and has limited effect on total off-label use. To investigate the evolution of paediatric off-label use after a therapeutically new group of medicines for a common condition becomes available for adults but is labelled for children with a delay of several years. Triptans were used as a model, because migraine is common in children, and is the only indication for triptans. Data on all triptan prescriptions 1994-2007 were extracted from the nationwide Finnish Prescription Register. Prescriptions for children were compared over time. Paediatric patients with triptan prescriptions increased from 204 in 1994 to 2618 in 2007. Sumatriptan accounted for 64% of all paediatric triptan prescriptions. When sumatriptan in a nasal formulation was labelled for children ≥ 12 years in 2003, off-label prescribing to younger children (6-11 years) doubled in 2003-2004. Sumatriptan on-label prescriptions increased to 728 adolescents (45% of sumatriptan in the age group) in 2007, but its off-label use continued also to increase to 1119 (61% of paediatric sumatriptan prescriptions) in 2007. In that year 72% of paediatric triptan use was off-label, 28% on-label. When a new significant medicine becomes available in adults, off-label use in children starts slowly but continues to extend to younger children reaching a market size which is little influenced by late appearance of a labelled product. Paediatric treatment remains dominated by off-label use despite labelling of a product in an age appropriate formulation to the most relevant age group.

Dynamics of long-term statin therapy

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. 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 3years, were followed-up until institutionalization, death, or 31 December 2007. Reinitiation rates after ≥180days 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 10years. 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 180days by the end of the follow-up period. Of the discontinuers, 46.7% restarted the treatment within 1year and 88.7% by the end of the follow-up. Of those followed up for ≥10years, 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 10years. 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.

Impact of out-of-pocket expenses on discontinuation of statin therapy: a cohort study in Finland

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

Validity of the Finnish Prescription Register for Measuring Psychotropic Drug Exposures among Elderly Finns

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

Arterial Intima-Media Thickness in 13-Year-Old Adolescents and Previous Antichlamydial Antimicrobial Use: A Retrospective Follow-up Study

Children with persistent Chlamydia pneumoniae infection may be at increased risk for atherosclerosis. The impact of antimicrobial therapy for primary prevention of atherosclerotic cardiovascular disease is unsolved. The purpose of this study was to determine whether treatment with antimicrobial agents effective against C pneumoniae during childhood, regardless of indication, has a favorable influence on the arterial wall-thickness in children by the time they reach adolescence. The association of macrolide, tetracycline, quinolone, and rifamycin use (number of exposure events) between ages 5 and 13 years with carotid and aortic intima-media thickness at age 13 years was investigated among 508 healthy children. Information about the use of medications was obtained from the Finnish prescription register. Arterial intima-media thickness was measured with a high-resolution ultrasound. Mean aortic intima-media thickness showed a significant direct association with the number of antichlamydial antimicrobial exposure events also after controlling for established atherosclerotic risk factors. Elevated C-reactive protein level had an additional effect on aortic intima-media thickness in a multivariable model. Carotid intima-media thickness was not associated with the number of preceding antichlamydial treatments. Recurrent antichlamydial treatments in childhood have no favorable influence on early vascular changes but are associated with increased intima-media thickness in the abdominal aorta. These findings suggest that the use of antimicrobial agents does not offer protection against the potential atherogenicity of repeated infectious insults.