What is behind the seeming cessation of the increase in sleep medicine consumption in Finland during the last years?

In Finland, between 2003 and 2010 and parallel to the increase in the prevalence of insomnia-related symptoms among the general population, there has been a cessation of growth and even a decrease in the consumption of traditional hypnotics. The reasons behind this seemingly paradoxical situation are not known. We analyzed trends over the period 2000-2010 in the estimated consumption of traditional hypnotics and some new drugs that are destined for use in insomnia treatment. We used the annual wholesale statistical database compiled by the Finnish Medicine Agency, FIMEA, and data from the Finnish Drug Prescription Register. We found evidence to support two parallel trends in Finnish outpatient care. First, there seems to be a trend in which physicians increasingly comply with official guidelines for insomnia treatment, which partly accounts for the decrease in the consumption of traditional hypnotics. Second, at the same time, the first trend seems to be resulting in an increasing trend to treat insomnia patients with some new drugs that were not originally developed for insomnia treatment by prescribing these non-hypnotic drugs in small, sub-clinical doses. The current trend in practice may have contradictory effects on the treatment of insomnia. The long-term consequences of using low doses of drugs other than hypnotics to treat insomnia are not known and the situation should, therefore, be followed-up in subsequent studies. However, pharmacological treatment should never be a substitute for non-pharmacological treatments of insomnia

Long-term changes in the incidence of childhood epilepsy. A population study from Finland

BackgroundThe incidence of childhood epilepsy has changed during the past decades, but it is unclear whether it increased or decreased.MethodsChanges in drug-treated childhood epilepsy between 1968 and 2012 were evaluated using the Finnish nationwide register of all children, aged ≤ 15 years, on antiepileptic drugs (AEDs) prescribed for the treatment of epilepsy. The first registered entitlement to full-refundable AEDs was used as a proxy for newly diagnosed epilepsy. Incidence densities were calculated as ratios of annual new cases per 100,000 person-years in each calendar year during 1968 to 2012.ResultsThe annual incidence density of newly treated childhood epilepsy increased from 35 in the 1960s to 87 per 100,000 person-years in the 1990s and decreased thereafter to 61 per 100,000 person-years. Since 1996, the incidence density decreased 1–2% per year in children aged ConclusionThe incidence of drug-treated childhood epilepsy from the late 1960s to the early 1990s distinctly increased. The reasons for the increase are not fully understood but may include increasing ascertainment through improved diagnosis and a wider acceptance of AED treatment. Since the 1990s, a slight decline can be seen, probably reflecting the recent improvement in child health and safety.</p

Trends in Early Outpatient Drug Therapy in Pediatric Inflammatory Bowel Disease in Finland: A Nationwide Register-Based Study in 1999–2009

Peer reviewe

Impact of early systemic lupus erythematosus on work disability-results from the Finnish nationwide register 2000-2007

Objectives of this study were to examine work disability (WD) and its leading causes in incident SLE patients. Data were derived from the Finnish nationwide registries to identify all non-retired, 18 to 64-year-old incident SLE patients between 2000 and 2007. Sick benefits and WD pensions and the causes for them were monitored until the end of 2008. A total of 446 working-aged, incident SLE patients available for work force (mean age 42 +/- 13 years, 89% females) were found. During the follow-up (median 5.3 years), WD pension was granted to 27 patients. The most common cause was SLE itself (14 patients, 52%), with cumulative incidence of 3.4% (95% CI 1.9 to 5.8) in 5 years and 5.0% (95% CI 3.0 to 8.5) in 8 years, followed by musculoskeletal and psychiatric causes. The age- and sex- adjusted incidence ratio for WD pension in SLE patients due to any cause was 5.4 (95% CI 3.7 to 7.9) compared to the Finnish population. The mean number of WD days was 32 (95% CI 28 to 35) per patient-year among all SLE patients during the follow-up. The study concludes that SLE patients have an increased risk for WD already in early course of the disease.Peer reviewe

Length of sickness absence and sustained return-to-work in mental disorders and musculoskeletal diseases : a cohort study of public sector employees

Objectives The aim of this study was to investigate the association between the length of sickness absence and sustained return to work (SRTW) and the predictors of SRTW in depression, anxiety disorders, intervertebral disc disorders, and back pain in a population-based cohort of employees in the Finnish public sector. Methods We linked data from employers' registers and four national population registers. Cox proportional hazards regression analysis with a cluster option was applied. SRTW was defined as the end of the sickness benefit period not followed by a recurrent sickness benefit period in 30 days. Results For depression, the median time to SRTW was 46 and 38 days among men and women, respectively. For anxiety disorders, the figures were 24 and 22 days, for intervertebral disc disorders, 42 and 41 days, and, for back pain, 21 and 22 days among men and women respectively. Higher age and the persistence of the health problem predicted longer time to SRTW throughout the diagnostic categories. Comorbid conditions predicted longer time to SRTW in depression and back pain among women. Conclusions This large cohort study adds scientific evidence on the length of sickness absence and SRTW in four important diagnostic categories among public sector employees in Finland. Further research taking into account, eg, features of the work environment is suggested. Recommendations on the length of sickness absence at this point should be based on expert opinion and supplemented with research findings.Peer reviewe

Cow's milk allergy in infancy and later development of type 1 diabetes-nationwide case-cohort study

Bakground: It is suggested that early intake of cow's milk could be a risk factor for type 1 diabetes (T1DM). Further, the different immunological background, gives a suggestion of an inverse relationship for the occurrence of these diseases. The aim of this study was to explore the association between cow's milk allergy (CMA) and the risk of T1DM in a register-based case-cohort study. Methods: Data were obtained from Finnish nationwide health registers. The study included all children born in Finland between January 01, 1986 and December 31, 2008 and diagnosed with T1DM before the age of 16 years (n = 7754). A 10% random sample from each birth year cohort was selected as a reference cohort (n = 137,798). T1DM, CMA, and asthma were defined based on valid special reimbursements for the costs of drugs/special formulas needed in the treatment of the diseases. Child's sex, birth decade, asthma, maternal diabetes and asthma, smoking during pregnancy, and previous deliveries were considered as confounding factors. Time-dependent, weighted Cox regression was applied for statistical analyses. Results: Children with CMA had an increased risk of developing T1DM in fully adjusted model (HR = 1.17; 95% CI 1.02-1.34), but the association was no longer observed when including the use of special infant formulas in the definition of CMA in the sensitivity analysis (HR = 1.11; 95% CI 0.92-1.32). CMA was associated with an increased risk of T1DM in children without asthma (HR = 1.27; 95%CI 1.10-1.47), but not in children with asthma (HR = 0.80; 95% CI 0.92-1.27). Conclusion: Children with CMA may have an increased risk of T1DM.Peer reviewe

Malignancies among newly diagnosed systemic lupus erythematosus patients and their survival

The objective of this study was to evaluate the incidence of malignancies among newly diagnosed systemic lupus erythematosus (SLE) patients compared to reference individuals. Another aim was to assess the survival of SLE patients with malignancy compared to references with malignancy. Finnish adult (>17 years) newly diagnosed SLE patients were identified by their drug reimbursement decisions made during 1.1.2000–31.12.2014 from the register of the Social Insurance Institution. For each case, three population controls were individually selected by age, sex and place of residence. Overall, 1006 SLE patients (women 84%), with a mean age of 45.5 years (SD 16 years) and 3005 population controls were linked to Finnish Cancer Registry, and the information about incident malignancies was retrieved from the day the special reimbursement decision for SLE medication was accepted (index day, ID) until 31.12.2018 or until death. The patients diagnosed with malignancy were followed up until 31.12.2019 considering survival. During the follow-up, 85 SLE patients (women 78%) and 192 controls (women 78%) had developed one or more malignancy after the ID. The incidence rate ratio for any malignancy was 1.41 (95% CI 1.08–1.85). The most common malignancy in SLE patients was non-Hodgkin lymphoma, with twelve cases. SLE patients with malignancy had a lower adjusted 15-year survival than controls with malignancy, 27.1% versus 52.4%, and the adjusted hazard ratio for death was 1.68 (95% CI 1.17–2.43). Our results confirm that SLE patients have a higher risk for overall malignancy. The results also suggest that SLE patients with malignancy have lower survival than their references with malignancy.publishedVersionPeer reviewe

Lactobacillus rhamnosus GG Intake Modifies Preschool Children's Intestinal Microbiota, Alleviates Penicillin-Associated Changes, and Reduces Antibiotic Use

Antibiotic use is considered among the most severe causes of disturbance to children's developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children's microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children's antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2-7. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children, causing an increase in the abundance of Prevotella, Lactococcus, and Ruminococcus, and a decrease in Escherichia. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use. The treatment, however, did reduce the frequency of gastrointestinal complaints after a macrolide course. Finally, the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use.Peer reviewe

Pregnancies in patients with systemic lupus erythematosus during 2000–2018 in Finland : a case–control study

Objectives: The aim was to investigate, how pregnancies proceed in patients with systemic lupus erythematosus (SLE) compared to their individually matched population controls. Material and methods: Adult incident SLE patients were identified from the register of new special reimbursement decisions for SLE drugs in 2000–2014. For each patient, 1–3 randomly selected controls from the Population Register Centre were matched. Data regarding pregnancies were obtained from the Finnish Medical Birth Register, Care Register and Register of Congenital Malformations until 2018. The study utilized data from the Drug Purchase Register and educational information from Statistic Finland. Results: A total of 163 deliveries for 103 mothers with SLE and 580 deliveries for 371 population controls were identified. The duration of pregnancies in SLE women was significantly shorter compared to controls (38.9 versus 39.6 weeks). There were more urgent Caesarean Sections. (15% versus 9%) and need for care at neonatal intensive care unit (NICU) (21% versus 11%) among deliveries in SLE mothers. No statistical difference was observed between SLE and control groups in the occurrence of preeclampsia or major congenital malformations. Gestational age was 2.5 weeks shorter when the mother experienced pre-eclampsia. Hydroxychloroquine was purchased by 30% of SLE mothers during pregnancy. Conclusion: The course of pregnancies in Finnish SLE patients seems to be quite moderate compared to controls, and no new safety issues were detected. The low utilization of hydroxychloroquine indicates that the benefits of the drug to pregnancy and disease course are not optimally recognized by specialists treating SLE mothers.Peer reviewe

Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children

Early-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome. However, little is known about the impacts of antibiotics on the developing microbiome of children. Here we use phylogenetics, metagenomics and individual antibiotic purchase records to show that macrolide use in 2-7 year-old Finnish children (N = 142; sampled at two time points) is associated with a long-lasting shift in microbiota composition and metabolism. The shift includes depletion of Actinobacteria, increase in Bacteroidetes and Proteobacteria, decrease in bile-salt hydrolase and increase in macrolide resistance. Furthermore, macrolide use in early life is associated with increased risk of asthma and predisposes to antibiotic-associated weight gain. Overweight and asthmatic children have distinct microbiota compositions. Penicillins leave a weaker mark on the microbiota than macrolides. Our results support the idea that, without compromising clinical practice, the impact on the intestinal microbiota should be considered when prescribing antibiotics.Peer reviewe