Initiating disease-modifying anti-rheumatic drugs rapidly reduces purchases of analgesic drugs in juvenile idiopathic arthritis.

Objective: To describe the use of analgesics 12 months before and after initiation of the first disease-modifying anti-rheumatic drug (DMARD) in children with juvenile idiopathic arthritis (JIA). Method: A register-based study linked three nationwide registers in Finland: the Register on Reimbursement for Prescription Medicines, the Drug Purchase Register (both maintained by the Finnish Social Insurance Institution), and the Finnish Population Register. The study ran from 1 January 2010 to 31 December 2014. It included 1481 patients aged < 16 years with diagnosed JIA and 4511 matched controls. Index day was the date when reimbursement for JIA medication was approved and treatment was initiated. The study period included 12 months pre- and post-index date, and purchases of prescription drugs were assessed for 3 month periods. Results: Non-steroidal anti-inflammatory drugs (NSAIDs) were purchased for 60% of the patients. Compared to controls, NSAID purchases for JIA patients were at their highest during the last 3 months before the index day [relative rate (RR) 21.2, 95% confidence interval (CI) 17.1-26.2], and they decreased steeply over the 10-12 months post-index (RR 4.0, 95% CI 3.1-5.0). Similar trends were seen with paracetamol and opioid purchases, but only 2% of patients purchased opioids during the 12 months pre-index and 1% during the 12 months post-index. Methotrexate was the most commonly used DMARD (91.9%), biologic DMARDs were used by 2.8% and glucocorticoids by 24.8% in the 3 months after the index day. Conclusion: Initiation of DMARDs rapidly reduces the need for analgesics in patients with JIA.

Declining trend in valproate use in Finland among females of childbearing age in 2012-2016 - a nationwide registry-based outpatient study.

BACKGROUND AND PURPOSE: Documented teratogenic effects of valproate (VPA) prompted restrictions of its use in females of childbearing age in 2014. We investigated possible annual changes in the outpatient use of VPA in Finland during 2008-2016 with a special focus on women. METHODS: We identified all outpatients with VPA purchases between 2008 and 2016 categorizing users due to epilepsy, bipolar disorder or miscellaneous indications. Temporal trends in the annual prevalence rates of VPA use were estimated using Poisson regression analyses. RESULTS: Between 2012 and 2016, the prevalence of VPA use among women aged 15-44 years decreased by 19%, from 50/10 000 to 40/10 000 (prevalence rate ratio, 0.81; 95% confidence intervals, 0.77-0.91; P < 0.001). The use of VPA due to epilepsy decreased significantly in females aged 15-24 and 25-34 years and that due to bipolar disorders decreased significantly in females aged 25-34 and 35-44 years. The use of VPA in the miscellaneous indication group decreased by 32% after 2014 in females aged 15-44 years and, most strikingly, by 56% among those aged 15-25 years. In women with epilepsy, the use of VPA increased among those over the age of 44 years. CONCLUSIONS: The rates of female VPA users with childbearing potential have decreased in all three major indication groups in Finland during recent years, especially after the European Medicines Agency restrictions were published in 2014. However, it still remains open to question as to whether the practice of VPA use follows current guidelines. A special concern is the relatively high prevalence of off-label use of VPA in fertile-aged females.

Declining trend in the incidence of biopsy-verified coeliac disease in the adult population of Finland, 2005-2014.

BACKGROUND: The frequency of coeliac disease (CD) has been on the rise over the past decades, especially in Western Europe, but current trends are unclear. AIM: To research the recent temporal changes in the incidence of adult, biopsy-verified coeliac disease and dermatitis herpetiformis (DH) in Finland, a country with a high frequency of coeliac disease. METHODS: All coeliac disease and DH cases diagnosed at age 20-79 years during 2005-2014 were retrieved from a nationwide database documenting all applicants for monthly compensation to cover the extra cost of maintaining a gluten-free diet. This benefit is granted on the basis of histology, not socioeconomic status. Temporal trends in the annual incidences were estimated using Poisson regression analyses. RESULTS: The total incidence of coeliac disease decreased from 33/100 000 during the years 2005-2006 to 29/100 000 during 2013-2014. The mean annual incidence of coeliac disease was nearly twice as high among women as among men, 42 vs 22 per 100 000, respectively. For middle- and old-aged women, the average rate of decrease in incidence was 4.8% (95% CI 3.9-5.7) per year and for men 3.0% (1.8-4.1) (P for linear trend <.001, for both). Similarly, the annual incidence of DH declined. For young adults, the rate of change remained low and nonsignificant throughout the period 2005-2014. CONCLUSIONS: Although the awareness of coeliac disease has increased during the past decades, the incidence of biopsy-verified diagnoses is not increasing, which suggests that exposure to yet unidentified triggering factors for coeliac disease has plateaued among the Finnish adult population.

The nationwide register-based prevalence of intellectual disability during childhood and adolescence.

BACKGROUND: Many studies have evaluated the prevalence of intellectual disability (ID) by focusing on different ages during childhood and adolescence. Although the prevalence of ID is higher in older age groups, how cumulative prevalence increases, and what level it reaches before adulthood, remains unclear. METHOD: We used Care Register for Health Care to retrieve information on individuals born in 1996-2007 with any of the inclusion diagnoses of ID (F7 group and/or aetiological diagnoses) for the period 1996 to 2013. The cumulative prevalence was calculated as percentages for every age based on Finnish population data. RESULTS: The registration of new diagnoses of ID continued steadily throughout the developmental years. The cumulative prevalence reached 1.19% by age 17.5 among those born in 1996. Later-born age groups appeared to receive their first ID diagnoses earlier in childhood. Those born in 1999 reached a cumulative prevalence of 1.21% already by age 14.5. Of all those with ID, 67% had an F7 diagnosis only, 42% had an aetiological diagnosis only and 9% had both diagnoses. CONCLUSIONS: Cumulative prevalence of ID by year, until the age of 18, will provide a better estimate and understanding of the prevalence of ID than a point prevalence at any one point during the developmental years.

Increased short- and long-term mortality in 8146 hospitalised peptic ulcer patients.

BACKGROUND: Incidence and complications of peptic ulcer disease (PUD) have declined, but mortality from peptic ulcer bleeding has remained unchanged. The few recent studies on mortality associated with both uncomplicated and complicated patients with peptic ulcer disease provide contradictory results. AIMS: To evaluate short- and long-term mortality, and the main causes of death in peptic ulcer disease. METHODS: In this retrospective epidemiologic cohort study, register data on 8146 adult patients hospitalised with peptic ulcer disease during 2000-2008 were collected in the capital region of Finland. All were followed in the National Cause of Death Register until the end of 2009. The data were linked with the nationwide Drug Purchase Register of the Finnish Social Insurance Institution. RESULTS: Mean follow-up time was 4.9 years. Overall mortality was substantially increased, standardised mortality ratio 2.53 (95% CI: 2.44-2.63); 3.7% died within 30 days, and 11.8% within 1 year. At 6 months, the survival of patients with perforated or bleeding ulcer was lower compared to those with uncomplicated ulcer; hazard ratios were 2.06 (1.68-2.04) and 1.32 (1.11-1.58), respectively. For perforated duodenal ulcers, both the short- and long-term survival was significantly impaired in women. The main causes of mortality at 1 year were malignancies and cardiovascular diseases. Previous use of statins was associated with significant reduction in all-cause mortality. CONCLUSIONS: One-year mortality in patients hospitalised with peptic ulcer disease remained high with no change. This peptic ulcer disease cohort had a clearly decreased survival rate up to 10 years, especially among women with a perforated duodenal ulcer, most likely explained by poorer survival due to underlying comorbidity.

Drugs used in incident systemic lupus erythematosus - results from the Finnish nationwide register 2000-2007.

The objectives of the study were to examine the initial, first-year anti-rheumatic outpatient therapy in patients with incident SLE, as well as the concomitant use of drugs for certain comorbidities, compared to the use in the general population. The Finnish nationwide register data on special reimbursements for medication costs was screened to identify the inception cohort of 566 adult SLE patients (87% females, mean age 46.5 ± 15.9 years) over the years 2000-2007. The patients were linked to the national Drug Purchase Register. Of those, 90% had purchased at least once some disease-modifying anti-rheumatic drugs (DMARDs) during the first year. Hydroxychloroquine was the most common (76%), followed by azathioprine (15%) and methotrexate (13%). With the exception of increase in mycophenolate mofetil, the proportions remained stable over the whole study period 2000-2007. Drugs for cardiovascular diseases, dyslipidemia, diabetes mellitus, hypothyroidism and obstructive pulmonary disease were more frequently purchased than in the sex- and age-adjusted population, with rate ratios ranging from 1.6 to 7.8. Over the years 2000-2007, almost all the patients with incident SLE in Finland started with a DMARD. Higher percentages of SLE patients were on medication for several common chronic diseases than in the population as a whole.

Maternal diet during pregnancy and lactation and cow's milk allergy in offspring.

BACKGROUND/OBJECTIVES: Diet during pregnancy and lactation may have a role in the development of allergic diseases. There are few human studies on the topic, especially focusing on food allergies. We sought to study the associations between maternal diet during pregnancy and lactation and cow's milk allergy (CMA) in offspring. SUBJECTS/METHODS: A population-based birth cohort with human leukocyte antigen-conferred susceptibility to type 1 diabetes was recruited in Finland between 1997 and 2004 (n=6288). Maternal diet during pregnancy and lactation was assessed by a validated, 181-item semi-quantitative food frequency questionnaire. Register-based information on diagnosed CMA was obtained from the Social Insurance Institution and completed with parental reports. The associations between maternal food consumption and CMA were assessed using logistic regression, comparing the highest and the lowest quarters to the middle half of consumption. RESULTS: Consumption of milk products in the highest quarter during pregnancy was associated with a lower risk of CMA in offspring (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.37-0.86; P<0.01). When stratified by maternal allergic rhinitis and asthma, there was evidence of an inverse association between high use of milk products and CMA in offspring of non-allergic mothers (OR 0.30, 95% CI 0.13-0.69, P<0.001). Cord blood IgA correlated positively with the consumption of milk products during pregnancy, indicating exposure to CMA and activation of antigen-specific immunity in the infant during pregnancy. CONCLUSIONS: High maternal consumption of milk products during pregnancy may protect children from developing CMA, especially in offspring of non-allergic mothers.

Psychiatric and cardiovascular comorbidities as causes of long-term work disability among individuals with recent-onset rheumatoid arthritis.

OBJECTIVES: With the ameliorating prognosis of rheumatoid arthritis (RA), the role of comorbidities as causes of work disability (WD) may increase. The aim of this study was to determine the contribution of psychiatric and cardiovascular (CV) comorbidities as the leading causes of long-term WD among patients with recent-onset RA. METHOD: Between 2000 and 2007, all incident, working-age and non-retired RA patients were identified from a Finnish nationwide register. From other registers, we identified the RA patients who were granted a permanent or temporary disability pension by 31 December 2008. The incidences of disability pensions with CV diseases (ICD-10 codes I00-I99) or psychiatric disorders (F20-F69) as the leading causes were assessed and compared with the general population. RESULTS: We identified a cohort of 7831 patients with RA. During follow-up, 1095 patients were granted a disability pension. After adjusting for competing risks, the 9-year cumulative incidence of WD caused by RA, a psychiatric comorbidity, or a CV disease was 11.9, 1.3, and 0.5%, respectively. Compared to the general population, the age- and sex-specific standardized incidence ratio (SIR) of WD due to psychiatric comorbidities was 0.99 [95% confidence interval (CI) 0.80-1.23] and due to CV disease 1.75 (95% CI 1.23-2.51). CONCLUSIONS: In the study cohort with recent-onset RA, the 9-year cumulative incidence of disability pensions caused by psychiatric or CV comorbidities was only 11% or 4%, respectively, of that caused by RA itself. Compared to the general population, the risk of WD due to CV disease was increased.

Prenatal and post-natal exposure to antibiotics and risk of asthma in childhood.

BACKGROUND: Evidence on the association between post-natal exposure to antibiotics and the development of asthma is extensive, but inconsistent and even less is known about prenatal exposure. OBJECTIVE: The aim of this study was to examine the associations between prenatal and post-natal exposure to different antibiotics and the risk of childhood asthma in a population- and register-based nested case-control study. METHODS: All children who were born in 1996-2004 in Finland and diagnosed with asthma by 2006 were identified from a national health register. For each case, one matched control was selected. Information on asthma diagnoses, purchased anti-asthmatic drugs and antibiotics as well as putative confounders was obtained from national health registries. The associations were analysed using conditional logistic regression for children diagnosed at the age of 3 years or later (n = 6 690 case-control pairs). RESULTS: Maternal use of any antibiotics during pregnancy was associated with an increased risk of asthma in the offspring [adjusted odds ratio (OR) = 1.31 (95% confidence interval (CI): 1.21-1.42)]. Several maternal specific antibiotics were associated with the risk of asthma, and the strongest association was observed for cephalosporins [OR = 1.46 (95% CI 1.30-1.64)]. Child's use of antibiotics during the first year of life was associated with an increased risk of asthma [OR = 1.60 (95% CI 1.48-1.73)]. Child's use of cephalosporins [OR = 1.79 (95% CI 1.59-2.01)], sulphonamides and trimethoprim [OR = 1.65 (95% CI 1.34-2.02)], macrolides [OR = 1.61 (95% CI 1.46-1.78)] and amoxicillin [OR = 1.46 (95% CI 1.35-1.58)] was associated with an increased risk of asthma. CONCLUSIONS AND CLINICAL RELEVANCE: Both prenatal and post-natal exposure to antibiotics was associated with an increased risk of asthma. The potential role of adverse effects of antibiotics on the gut microbiota and the development of asthma should be further explored.

Mortality and causes of death among incident cases of systemic lupus erythematosus in Finland 2000-2008.

The objectives of the study were to investigate mortality and causes of death in patients with recent-onset systemic lupus erythematosus (SLE) in Finland. Data for patients with SLE for the study were collected (2000-2007) from the nationwide register on decisions of special reimbursements for drugs, maintained by the Social Insurance Institution (SII) in Finland. Data on deaths of the patients were obtained from the official death certificate statistics of Statistics Finland until the end of 2008. Of the 566 incident SLE patients, median follow-up time was 5.4 (IQR 3.3, 7.1) years, and 30 patients (23 females, seven males) died in the years 2000 through 2008. Mean age at death was 67.8 ± 17.2 years for females and 62.3 ± 15.2 years for males. The 5-year survival rates were 94.8% (95%CI 92.0-96.6%) and 88.2% (95%CI 76.5-94.3%), respectively. The age- and sex-adjusted standardized mortality ratio was 1.48 (95%CI 1.01-2.12). Primary causes of death were cardiovascular diseases, malignancy and SLE itself. In conclusion, survival of the patients with SLE was inferior to that of the general population. Cardiovascular diseases were responsible for 37% of deaths.

Antidepressant use among persons with recent-onset rheumatoid arthritis: a nationwide register-based study in Finland.

OBJECTIVES: The aim of this study was to investigate antidepressant use in a nationwide cohort of persons with incident rheumatoid arthritis (RA) in 2000-2007 in Finland. METHOD: Register data from the Social Insurance Institution of Finland were used to evaluate antidepressant use in ≥ 50-year-old incident RA patients (n = 10,356) and the same-age general population. RESULTS: Of the RA patients, 10.0% (n = 1034) had used antidepressants during the year preceding RA diagnosis. The cumulative incidence of antidepressant initiations after RA diagnosis was 11.4% [95% confidence interval (CI) 10.0-12.9] for men and 16.2% (95% CI 14.9-17.5) for women at the end of follow-up (mean 4.4 years). Female gender [age-adjusted hazard ratio (HR) 1.39, 95% CI 1.21-1.60] and increasing number of comorbidities (p for linearity < 0.001) predicted antidepressant initiations. In the last follow-up year, antidepressant use was at the same level among men with RA [prevalence rate ratio (PRR) 0.93, 95% CI 0.82-1.06] but lower among women (PRR 0.89, 95% CI 0.83-0.95) when compared to the general population. CONCLUSIONS: Antidepressant initiations in early RA were associated with female gender and comorbidity. Although depression is stated to be a sizeable problem in RA, the prevalence of antidepressant use did not exceed the population level.

Incidence and complications of peptic ulcer disease requiring hospitalisation have markedly decreased in Finland.

BACKGROUND: The characteristics of peptic ulcer disease (PUD) are changing. AIM: To evaluate time trends in the incidence of PUD and its complications in hospitalised patients at the beginning of the 21st century, drug therapies in out-patient care as a risk factor for recurrent PUD, and medication used by PUD patients compared with the background population. METHODS: In this retrospective epidemiologic cohort study, data from the years 2000-2008 came from The Hospital District of Helsinki and Uusimaa, and the Finnish Care Register. All hospitalised adult patients with PUD in the capital region of Finland were included. The data were linked with nationwide Prescription Register of the Finnish Social Insurance Institution allowing detailed individual medicine purchase data. RESULTS: A total of 9951 peptic ulcers were detected among 8146 individual patients during the study period. The mean annual incidence of all peptic ulcers decreased from 121/100,000 (95% CI: 117-125) in 2000-2002, to 79 (95% CI: 76-82) in 2006-2008 [Incidence rate ratio = 0.62 (95% CI: 0.58-0.64), P < 0.001 after age and sex adjustment]. Decrease in incidence was seen in all age groups and in both sexes. The overall rate of severe complications of PUD was reduced. One-year cumulative incidence of recurrent ulcers was 13%. Use of several drugs was associated with increased risk for recurrence. The purchases of various drugs were more common among PUD patients compared with background population. CONCLUSIONS: Both the incidence and complication rates have markedly decreased during the study period. Recurrent peptic ulcer disease was associated with polypharmacy.

Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease.

BACKGROUND: Refractory coeliac disease (RCD) is thought to be a rare disorder, but the accurate prevalence is unknown. AIM: We aimed to identify the prevalence of and the risk factors for developing RCD in a Finnish population where the clinical detection rate of coeliac disease is high. METHODS: The study involved 11 hospital districts in Finland where the number of treated RCD patients (n = 44), clinically diagnosed coeliac disease patients (n = 12 243) and adult inhabitants (n = 1.7 million) was known. Clinical characteristics at diagnosis of coeliac disease between the RCD patients and patients with uncomplicated disease were compared. RESULTS: The prevalence of RCD was 0.31% among diagnosed coeliac disease patients and 0.002% in the general population. Of the enrolled 44 RCD patients, 68% had type I and 23% type II; in 9% the type was undetermined. Comparing 886 patients with uncomplicated coeliac disease with these 44 patients that developed RCD later in life, the latter were significantly older (median 56 vs 44 years, P < 0.001), more often males (41% vs. 24%, P = 0.012) and seronegative (30% vs. 5%, P < 0.001) at the diagnosis of coeliac disease. Patients with evolving RCD had more severe symptoms at the diagnosis of coeliac disease, including weight loss in 36% (vs. 16%, P = 0.001) and diarrhoea in 54% (vs. 38%, P = 0.050). CONCLUSIONS: Refractory coeliac disease is very rare in the general population. Patients of male gender, older age, severe symptoms or seronegativity at the diagnosis of coeliac disease are at risk of future refractory coeliac disease and should be followed up carefully.

Age-specific prevalence of intellectual disability in Finland at the beginning of new millennium--multiple register method.

BACKGROUND: In the national study of multiple registers in 2000, the average prevalence of intellectual disability (ID) was 0.70%, with marked differences by age group (range 0.38-0.96%) - what are these differences in detail, and can they be understood? METHOD: This study was based on two national health registers and six social benefit registers. Prevalence of ID was calculated by 1-year age cohorts. RESULTS: The multiple register prevalence of ID increased steadily from 0.20% in the first life year to 0.74% (male: 0.90%, female: 0.58%) at 10 years. For boys, the rate fell to 0.71% at 11 years. For both sexes, a steady increase was noted in the distribution up to 40 years (male: 0.84%, female: 0.73%), followed by a sharper increase to the maximum prevalence (male: 1.19% at 48 years, female: 1.05% at 50 years). At the pension age of 66 years, a sudden drop to 0.49% occurred for men and women. Different registers gave very different age distributions. CONCLUSIONS: By examining the data by 1-year age cohorts, and by understanding the role of each register, it could be deduced that a proportion of cases in younger age groups is lacking, and a remarkable proportion of elderly ID persons is missing from the pooled data. The findings were more difficult to interpret, if the data were grouped into bigger age groups.