Finnish Register Research Articles

Characterizing disease burden and health care resource utilization in patients with hypertrophic cardiomyopathy: a nationwide real-world study in Finland

Abstract Background Hypertrophic cardiomyopathy (HCM) is an often hereditary myocardial disease with an estimated prevalence of 1:500 in the general population. Purpose This study aimed to investigate healthcare resource utilization (HCRU) and associated costs in patients diagnosed with HCM (and the associated subtypes: obstructive or non-obstructive) in a nationwide cohort in Finland. Methods This retrospective, registry-based cohort study included all Finnish patients diagnosed with HCM between 2000 and 2021, who were 12+ years old at the time of diagnosis, as identified from the national care registers for healthcare. HCRU data were collected between 2014 and 2021 from the Finnish national care registers for health care and the social insurance institution. Data pertaining to New York Heart Association (NYHA) classification were collected from three Finnish university hospitals. Results The study cohort comprised 5,834 patients with an HCM diagnosis; obstructive HCM accounted for 34% of cases. Mean per patient-year costs were €6638, 95% confidence interval (CI) €6472-€7415, and €6112, 95% CI €5957-€6560 for those with obstructive and non-obstructive HCM respectively. All-cause hospitalizations at specialized care were the most prominent cost associated with patients with obstructive and non-obstructive HCM equating to 46.3% and 46.1% of the total cost respectively (Fig 1.). Comorbidity burden, as measured by Charlson comorbidity index (CCI) score, was greater in patients with the obstructive than non-obstructive phenotype of the disease (CCI ≥4: 2.2 and 1.8, p<0.01, respectively). The highest utilization of invasive procedures was found for patients with NYHA class III-IV. Conclusion This population-based study, utilizing real-world data, provides novel insights into HCRU and related costs among Finnish patients with HCM (and associated subtypes). HCRU appears to be primarily driven by hospitalizations at specialized care. Furthermore, the data indicate that patients with obstructive HCM are likely to have a more severe disease, with higher comorbidity burden and requiring more invasive procedures than patients with the non-obstructive form of the disease. However, there were no statistically significant differences in health care costs between those with obstructive and non-obstructive HCM.

Maternal Eating Disorders, Body Mass Index, and Offspring Psychiatric Diagnoses

Maternal nutrition is essential in fetal development; thus, disordered eating may influence this process and contribute to the development of offspring psychiatric disorders. To investigate the association of maternal eating disorders and prepregnancy body mass index (BMI) with offspring psychiatric diagnoses. This population-based cohort study used Finnish national registers to assess all live births from January 1, 2004, through December 31, 2014, with follow-up until December 31, 2021. The data analyses were conducted from September 1, 2023, to September 30, 2024. Maternal eating disorder and prepregnancy BMI. Primary outcomes were 9 neurodevelopmental and psychiatric offspring diagnoses. Cox proportional hazards modeling adjusted for potential risk factors in the development of the outcome disorders was applied in 2 models. Secondary analyses were stratified for adverse birth outcomes (prematurity, small size for gestational age, and low Apgar score) or comorbid offspring eating disorders. Categories of BMI (calculated as weight in kilograms divided by height in meters squared) included underweight (BMI <18.5), normal weight (18.5-24.9), overweight (25.0-29.9), obesity (30.0-34.9), and severe obesity (≥35.0). The mean (SD) age of 392 098 included mothers was 30.15 (5.38) years, 42 590 mothers (10.86%) were born outside of Finland, 6273 mothers (1.60%) had a history of an eating disorder, 23 114 mothers (5.89%) had prepregnancy underweight, and 208 335 (53.13%) mothers had overweight or obesity. Among 649 956 included offspring, 332 359 (51.14%) were male, and 106 777 (16.43%) had received a neurodevelopmental or psychiatric diagnosis. Maternal eating disorders, prepregnancy underweight, and overweight or obesity were associated with most of the studied mental diagnoses in offspring, even after adjusting for potential covariates. The largest effect sizes were observed for maternal eating disorders not otherwise specified in association with offspring sleep disorders (hazard ratio [HR], 3.34 [95% CI, 2.39-4.67]) and social functioning and tic disorders (HR, 2.79 [95% CI, 2.21-3.52]), while for maternal severe prepregnancy obesity, offspring intellectual disabilities (HR, 2.04 [95% CI, 1.83-2.28]) had the largest effect size. Adverse birth outcomes further increased the risk of offspring having other feeding disturbances of childhood and infancy (eg, HR, 4.53 [95% CI, 2.97-6.89] for maternal eating disorders) and attention-deficit/hyperactivity disorder and conduct disorder (eg, HR, 2.27 [95% CI, 1.74-2.96] for maternal anorexia nervosa). In this population-based cohort study including 392 098 mothers and 649 956 offspring, offspring from mothers with an eating disorder history or prepregnancy BMI outside normal weight were at higher risk of psychiatric disorders. The results differed somewhat between the 2 exposures with regard to which offspring diagnoses had associations, and effect sizes were typically larger for maternal eating disorders vs BMI. These findings suggest a need to consider these 2 exposures clinically to help prevent offspring mental illness.

Stability of Cloninger's temperament traits following a health event: Subjective and objective health status analysis from the Northern Finland Birth Cohort 1966

Personality/temperament traits are often presumed to remain stable across various life outcomes. This longitudinal study challenges this assumption by examining changes of Cloninger's Temperament and Character Inventory traits following a severe health event, utilizing data from the population-based Northern Finland Birth Cohort 1966, combined with Finnish register data (N = 3195). We explore both health conditions diagnosed in healthcare settings and changes in individuals' self-reported health to discern the relationship between alterations in objective and subjective health and changes in temperament traits between ages 31 and 46. Our findings suggest that changes in health generally don't relate to alterations in three of the four temperament traits—novelty seeking, reward dependence, and persistence. However, we observe a significant shift in the fourth temperament trait, harm avoidance, following a health change. Both females and males reporting a decline in self-reported health become significantly more harm avoidant, irrespective of whether they experience an objective health event. Our results indicate that harm avoidance may not be entirely stable over time, and health changes, particularly regarding subjective health, are linked to variations in harm avoidance. Our results emphasize the need for caution when using harm avoidance as a predictor, particularly in the context of diverse health outcomes.

MyMS: An Interface for Patient-Reported Outcomes for Finnish Individuals With Multiple Sclerosis.

Patient-generated data are a cornerstone of individualized multiple sclerosis (MS) treatment. MyMS, an interface for patient-reported outcomes (PROs) was developed by the Finnish MS Register to enable systematic collection of PROs. MyMS collects data on demographics, lifestyle factors, disease-related factors, and validated questionnaires, including the Quality of Life Questionnaire (15D), the Multiple Sclerosis Impact Scale (MSIS-29), and the Fatigue Severity Scale (FSS). At the end of 2020, the patient-reported Expanded Disability Status Scale (PREDSS), the EuroQOL-5 Dimension (EQ-5D), the Fatigue Scale for Motor and Cognitive Functions (FSMC), and the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) were added. As of January 1, 2023, 1201 individuals with MS (79% female) have added data to MyMS. Of the validated PRO measures (PROMs), the 15D, MSIS-29, and FSS are the most used. The mean PREDSS score is 3.0 and median disease duration is 6.4 years. According to the existing PROMs, patients report mildly compromised quality of life and problems with fatigue and cognition. The patient interface of the Finnish MS Register consists of data from 17 of 21 counties with well-being services. The interface is used by 10% of Finnish individuals with MS. The addition of the PREDSS, EQ-5D, FSMC, and MSNQ to the interface has increased health care professional and patient interest in the use of PROMs. We suggest that PROs should be integrated into electronic health records to improve shared decision-making and diminish documentation burden.

Participation in formal adult education and family life—a gendered story

Abstract Previous literature on adult education (AE) has focused on various aspects of social inequalities, and although many acknowledge the critical role of gender, the mechanisms influencing gender differences in participation are rarely to the fore. Specifically, women report family responsibilities as the main reason for not enrolling in AE. This article examines whether family responsibilities, measured as the age and number of children, act as motivators or barriers to formal AE participation differently among men and women with varying time and monetary resources, that is, partnership status and relative income, in two societies with high formal AE enrolment rates; Finland and Great Britain. The results from Finnish registers and Understanding Society for 1998–2019 demonstrate clearly that family responsibilities related to having young children in the household restrict women from participating in formal AE to a greater extent than men in both countries. Further, while Finnish society enables individuals who traditionally have fewer resources to attend formal AE, that is, single parents and larger families, in Britain, formal AE is mainly taken up by individuals without children or those in stable family situations. The results highlight the importance of institutions in providing equal access to further educational qualifications.

Changes in Chlamydia trachomatis risk before and after union formation and separation among women of reproductive age.

Not having an established relationship is associated with an elevated risk of Chlamydia trachomatis (CT) infection, but this might reflect selection into and out of unions. Although union formation and union separation are common events in reproductive age, little is known about changes in CT risk before and after these transitions. We linked Finnish Population Register data to the National Register of Infectious Diseases and used fixed-effects linear probability models that account for all time-invariant confounders to examine changes in women's 6-month CT risk 3 years before and 3 years after entry into first cohabitation (n = 293554), non-marital separation (n = 201647) or marital separation (n = 92232) during 2005-14. From 3 years to 1 year before first union formation, the 6-month risk of CT increased slightly, peaking at 1.27% immediately prior to union formation (95% confidence interval 1.22-1.31). It declined sharply following union formation, being only 0.40% (0.34-0.46) 6-12 months after union formation with little changes thereafter. Among women separating from non-marital unions, the risk increased from 0.50% (0.42-0.57) to 1.45% (1.40-1.49) around the time of separation and decreased following separation. The pattern of findings was relatively similar for marital separation, although the observed risks and changes were smaller in magnitude. Our results based on longitudinal data and individual fixed-effects models indicate that the period immediately after separation may be causally associated with an elevated risk of CT. This suggests that recently separated women should be identified as a high-risk group for CT.

High Burden of Ileus and Pneumonia in Clozapine-Treated Individuals With Schizophrenia: A Finnish 25-Year Follow-Up Register Study.

The authors used longitudinal biobank data with up to 25 years of follow-up on over 2,600 clozapine users to derive reliable estimates of the real-world burden of clozapine adverse drug events (ADEs). A total of 2,659 participants in the FinnGen biobank project had a schizophrenia diagnosis and clozapine purchases with longitudinal electronic health record follow-up for up to 25 years after clozapine initiation. Diseases and health-related events enriched during clozapine use were identified, adjusting for disease severity. The incidence and recurrence of ADEs over years of clozapine use, their effect on clozapine discontinuation and deaths, and their pharmacogenetics were studied. Median follow-up time after clozapine initiation was 12.7 years. Across 2,157 diseases and health-related events, 27 were enriched during clozapine use, falling into five disease categories: gastrointestinal hypomotility, seizures, pneumonia, other acute respiratory tract infections, and tachycardia, along with a heterogeneous group including neutropenia and type 2 diabetes, among others. Cumulative incidence estimates for ileus (severe gastrointestinal hypomotility) and pneumonia were 5.3% and 29.5%, respectively, 20 years after clozapine initiation. Both events were significantly associated with increased mortality among clozapine users (ileus: odds ratio=4.5; pneumonia: odds ratio=2.8). Decreased genotype-predicted CYP2C19 and CYP1A2 activities were associated with higher pneumonia risk. Clozapine-induced ileus and pneumonia were notably more frequent than has previously been reported and were associated with increased mortality. Two CYP genes influenced pneumonia risk. Pneumonia and ileus call for improved utilization of available preventive measures.

The incidence of visual impairment due to retinitis pigmentosa has declined in Finland over the last 40 years.

To study the changes in incidence, age at onset and severity of visual impairment (VI) due to retinitis pigmentosa (RP) in the Years 1980-2019, and the incidence and age at diagnosis of hereditary retinal dystrophy (HRD) diagnoses coded by ICD10 H35.5 in the Years 1998-2019 in Finland. A total of 1606 persons with VI due to RP registered by the Finnish Register of Visual Impairment and total of 4291 HRD diagnoses registered by the Care Register of the Finnish Institute for Health and Welfare were included. VI was classified according to the Finnish national definitions derived from the WHO definitions. The significance of the changes in incidence and age at onset were tested with statistical tests (Kruskal-Wallis, Mann-Whitney U and Cochran-Armitage). Two-tailed p-value below 0.05 was considered significant. The incidence of VI due to RP has decreased from 0.96/100 000 in the 1980s to 0.55/100 000 in the 2010s (p 0.004). The age at onset of VI has increased from 41.6 to 50.3 years. The severity of VI has not changed. The incidence of HRD diagnoses has decreased from 3.66/100 000 in the 2000s to 2.86/100 000 in the 2010s (p 0.024). The age at diagnosis has risen in male patients from 42.1 to 44.5 years (p 0.024). The VI caused by RP in Finland has decreased. It develops at an older age than in the past. We hypothesize that this trend may be attributed to informed decisions by visually impaired persons to refrain from having offspring to prevent the transmission of hereditary mutations. The severity of VI due to RP has remained relatively unchanged. The incidence of HRD diagnoses has decreased, and the diagnosis occurs at an older age among men.

Parental psychopathology and offspring anxiety disorders in childhood and adolescence: A Finnish nationwide register study

BackgroundResearch suggests an association between parental psychiatric disorders and offspring anxiety disorders, yet comprehensive studies are limited. This study aims to investigate the associations between various parental psychiatric disorders and anxiety disorders in their offspring. MethodUsing Finnish register data, this nested case-control study analyzed 867,175 singleton live births from 1992 to 2006, identifying 21,671 cases of anxiety disorders diagnosed between 1998 and 2016. Matched with four controls each (n = 72,414) based on age and biological sex, the study adjusted for demographic and prenatal factors using conditional logistic regression models to calculate odds ratios (aORs). ResultsThere was a significant association between parental psychiatric disorders and increased risk of anxiety disorders in offspring. The risk was notably higher when both parents had psychiatric disorders (aOR = 5.04; 95 % CI, 4.70‐5.39; p < .001). Maternal psychiatric disorders were strongly associated with offspring anxiety than paternal disorders (aOR 1.52; 95 % CI 1.43–1.61; p < .001). This association was consistent regardless of timing of parental diagnosis. Significant associations were observed between any parental psychiatric disorder and increased risks in offspring for specific phobia, social phobia, generalized anxiety disorder, separation anxiety, and panic disorder. Maternal psychiatric disorders showed elevated risk for panic disorder and social phobia among girls and separation anxiety and generalized anxiety among boys. ConclusionThe findings emphasize the significant impact of parental psychiatric health on offspring anxiety disorders, highlighting the influence of genetic and environmental factors. Addressing parental mental health is crucial in preventing childhood anxiety disorders.

Effectiveness of Baricitinib Risk Minimization Activities in Patients With Rheumatoid Arthritis—A Cohort Study in Four Nordic Countries

ABSTRACTIntroductionBaricitinib received European Medicines Agency (EMA) approval for the treatment of moderate‐to‐severe active rheumatoid arthritis (RA) in 2017. Due to risks including serious infections, increased blood lipid parameters, and missing information regarding safety in pregnancy, additional risk minimization measures (aRMM) including healthcare professional educational material and a patient alert card were implemented to inform on the risks and actions to minimize risk such as the need to screen for tuberculosis and active viral hepatitis before starting baricitinib, monitoring of blood lipids and against use during pregnancy. The aim of the study is to report occurrences of infections, lipid level monitoring and pregnancies, in real world data, to gain insights into whether baricitinib is used in accordance with the aRMM.MethodsA descriptive observational cohort study, utilizing routinely collected data from the Swedish, Norwegian, Finnish, and Danish national registries, was carried out. RA patients initiating baricitinib treatment were identified in the periods 2017–19 (Sweden and Finland), 2017–20 (Norway) and 2017–21 (Denmark). Monitored events included pregnancies, cases of tuberculosis, viral hepatitis, and hyperlipidemia, as well as changes in statin prescriptions (including any of initiation, escalation, reduction or change of statin). Hyperlipidemia and statin use served as proxies for lipid level assessment.ResultsAmong 3908 patients initiating baricitinib (3373 person‐years exposure), eight pregnancies (1% of 815 women aged 18–50 years) potentially overlapped with treatment. During baricitinib treatment, there was a small number of prevalent cases of tuberculosis (less than three events), and a low prevalence of hepatitis (0.2%), and hyperlipidemia (0.5%), whereas 9.3% had start of or changes in statin prescription, indicating lipid level monitoring.ConclusionThe study's findings suggest that patients with RA are treated with baricitinib in accordance with the risk minimization recommendations, particularly concerning pregnancy and infection risks. However, the methods used for assessing lipid levels warrant further refinement for more accurate monitoring.

Psychotherapy use among migrants: a register-based longitudinal study

BackgroundMigrants use less mental health services compared with non-migrant populations, but there is very little information on the use of long-term psychotherapy among migrants. Finnish register data allow for studying...

Women's health study (WENDY) - a protocol of a population-based study assessing gynecological and metabolic health in women in their mid-30s.

The Women's Health Study (WENDY) was conducted to improve insights into women's health and health burden. It provides a unique, comprehensive data source that can be broadly utilised to understand gynaecological symptoms, diseases, and their relation to metabolic and overall health more deeply in a population-based setting. The study was conducted in Finland from May 2020 to October 2022. It included 1,918 women (33-37 years old) who were born in Northern Finland between July 1985 and December 1987. Data collection comprised one three-to-four-hour study visit that included clinical measurements, biological samples, ultrasound examinations and an extensive questionnaire on gynaecological and reproductive history, physical and mental health, quality of life, lifestyles, current life situations, health awareness and opinions. The study also included a menstrual cycle follow-up and cognitive testing up to three months via a mobile application. Given that all participants' data can be linked to all Finnish national registers, and the NFBC participants' data can be linked to the birth cohort data set collected from gestational week 24 onwards, WENDY study forms one of the largest datasets worldwide to investigate gynecological and metabolic health burden in women.

Survival improvements in esophageal and gastric cancers in the Nordic countries favor younger patients.

Esophageal cancer (EC) and gastric cancer (GC) are fatal cancers with a relatively late age of onset. Age is a negative risk factor for survival in many cancers and our aim was to analyze age-specific survival in EC and GC using the recently updated NORDCAN database. NORDCAN data originate from the Danish, Finnish, Norwegian, and Swedish nationwide cancer registries covering years 1972 through 2021 inviting for comparison of 50-year survival trends between the countries. Relative 1- and 5-year survival and 5/1-year conditional survival (i.e., survival in those who were alive in Year 1 to survive additional 4 years) were analyzed. Survival in EC showed large gains for patients below age 80 years, 5-year survival in Norwegian men reaching 30% and in women over 30% but for 80-89 year old survival remained at 10%. In contrast, hardly any gain was seen among the 80-89 year patients for 1-year survival and small gains in 5 year and 5/1-year survival. Survival gaps between age-groups increased over time. For GC there was also a clear age-related negative survival gradient but the survival gaps between the age groups did not widen over time; Norwegian male and female 5-year survival for 80-89 year old was about 20%. The age-specific survival difference in GC arose in Year 1 and did not essentially increase in 5-year survival. While there were differences in survival improvements between the countries, poor survival of the 80-89 year old patients was shared by all of them. To conclude, survival has improved steadily in younger GC and EC patients in most Nordic countries. While the 80-89 year old population accounts for nearly a quarter of all patients and their poor survival depressed overall survival, which can therefore be increased further by improving diagnostics, treatment and care of elderly EC and GC patients.

The Association of Metformin, Other Antidiabetic Medications, and Statins with the Prognosis of Hepatocellular Carcinoma in Patients with Type 2 Diabetes: A Retrospective Cohort Study.

This study aimed to explore whether the prediagnostic use of metformin and statins is associated with the prognosis of patients with hepatocellular carcinoma (HCC) and type 2 diabetes. We identified 1383 eligible individuals who had both type 2 diabetes and HCC diagnosed between 1998 and 2017 from several Finnish registers. Cox models were fitted for cause-specific and all-cause mortality in relation to the use of antidiabetic medications and statins prior to the HCC diagnosis. Prediagnostic metformin use was associated with decreased overall mortality (hazard ratio 0.84, 95% confidence interval 0.74-0.94) compared with nonuse in patients with type 2 diabetes. Similarly, slightly decreased HCC mortality and other-cause mortality were observed among metformin users. The results were inconclusive regarding metformin use and both overall and HCC mortality among patients with localized HCC. No discernible contrast between statin users and nonusers was found in overall mortality nor HCC mortality in either the whole cohort or patients with localized cancer.

Regional variations in incidence and treatment trends of Achilles tendon ruptures in Finland: a nationwide study.

The aim of our study was to assess the regional variations in Achilles tendon rupture incidence and treatment methods in Finland during the period 1997-2019. The Finnish National Hospital Discharge Register (NHDR) and the Finnish Register of Primary Health Care Visits (PHCR) were searched to identify all adult patients diagnosed with Achilles tendon rupture during our study period. The population-based annual incidence and incidences of surgically and non-surgically treated Achilles tendon ruptures were calculated for each hospital district. Achilles tendon rupture incidence increased from 17.3 per 105person-years in 1997 to 32.3 per 105in 2019. The mean incidence of Achilles tendon ruptures ranged from 26.4 per 105(North Savo) to 37.2 per 105(Central Ostrobothnia). The incidence of Achilles tendon ruptures increased in all areas. The proportion of non-surgical treatment of Achilles tendon ruptures ranged in 1997 from 7% (Vaasa) to 67% (Åland) and in 2019 from 73% (Southwest Finland) to 100% (East Savo, Kainuu, Länsi-Pohja, Åland). During the study period, a shift towards non-surgical treatment was evident in all hospital districts. Regional variations in Achilles tendon rupture incidence exist in Finland; however, the incidence increased in all areas during the follow-up period. More Achilles tendon rupture patients are currently being treated non-surgically throughout the country.

Register-based study on prescription renewal without the prescriber meeting the patient.

Renewing prescriptions is important for the continuity of pharmacotherapy. However, renewing without the prescriber meeting the patient might lead to insufficient pharmacotherapy monitoring. This study investigated the prevalence of renewed prescriptions, prescriptions renewed without the prescriber meeting the patient and the factors associated with renewals made without meeting the patient. This register-based study employed data on electronic prescriptions and health care contacts from Finnish registers. Prescriptions were classified as renewed if there was a renewal request or a previous prescription for the same ATC code. Prescriptions were considered as being renewed without meeting the patient if there was no patient contact on the renewal date. Descriptive and logistic generalized estimating equation analyses were conducted. The random sample of prescriptions (10%) from the year 2019 amounted to 2 804 048. Of these, 41.9% were original, 35.4% were renewals without meeting the patient and 22.7% were renewed with meeting the patient. Characteristics such as male sex, age 35-54 years, prescription for cardiovascular system preparations and the prescription being renewed during the summer (June-August) were associated with renewals made without meeting the patient. Further research is needed on the implementation of pharmacotherapy monitoring in the case of renewals without the prescriber meeting the patient.

Somatic and psychiatric comorbidity in people with diagnosed gambling disorder: A Finnish nation-wide register study.

This is the first nation-wide register study based on a total population sample measuring the gender-specific incidences of chronic diseases and conditions among adults diagnosed with gambling disorder (GD). The study used aggregated data for 2011-22 retrieved from the Register of Primary Health Care visits, Care Register for Health Care and Care Register for Social Welfare, including specialized outpatient and inpatient health care, inpatient social care and institutional care and housing services with 24-hour or part-time assistance, set in mainland Finland. Participants comprised people aged 18-90+ years with GD diagnosis [corresponding to pathological gambling, International Classification of Diseases 10th revision (ICD-10) code F63.0, n = 3605; men n = 2574, women n = 1031]and the general population (n = 4 374 192). Incidences of somatic diseases and psychiatric disorders were calculated for the people with diagnosed GD and for the general population, separately for women and men. After standardizing for age, the incidence of each diagnostic group was systematically higher for people with GD compared with the general population, except for cancer. The highest standardized incidence ratio (SIR) values were for psychiatric disorders [SIR = 234.2; 95% confidence interval (CI) = 226.1-242.4], memory disorders (SIR = 172.1; 95% CI = 119.1-234.8), nervous system diseases (SIR = 162.8; 95% CI = 152.8-173.1), chronic respiratory diseases (SIR = 150.6; 95% CI = 137.6-164.2), diabetes (SIR = 141.4; 95% CI = 127.9-155.5) and digestive diseases (SIR = 134.5; 95% CI = 127.1-142.2). In Finland, the incidence of chronic diseases and conditions among people with gambling disorder is higher compared with the general population, apart from cancer.

Predicting Alzheimer’s disease from cognitive footprints in mid and late life: How much can register data and machine learning help?

BackgroundReal-world data with decades-long medical records are increasingly available alongside the growing adoption of machine learning in healthcare research. We evaluated the performance of machine learning models in predicting the risk of Alzheimer’s disease (AD) using data from the Finnish national registers. MethodsWe conducted a case-control study using data from the Finnish MEDALZ (Medication use and Alzheimer’s disease) study. Altogether 56,741 individuals with incident AD diagnosis (age ≥ 65 years at diagnosis and born after 1922) and their 1:1 age-, sex-, and region of residence-matched controls were included. The association of risk factors, evaluated at different age periods (45–54, 55–64, 65+), and AD were assessed with logistic regression. Predictive accuracies of logistic regressions were compared with seven machine learning models (L1-regularized logistic regression, Naive bayes, Decision tree, Random Forest, Multilayer perceptron, XGBoost, and LightGBM). Findings63.5 % of cases and controls were females and the mean age was 79.1 (SD = 5.1). The strongest associations with AD were observed for head injuries at age 55–64 (OR, 95 % CI 1.33, 1.19–1.48) and 65+ (1.31, 1.23–1.40), followed by antidepressant use (1.30, 1.22–1.38) at 55–64 and antipsychotic use (1.27, 1.19–1.35) at 65+. The predictive accuracies of all models were low, with the best performance (AUC 0.603) observed in Random Forest for predicting AD onset at age 65–69. InterpretationAlthough significant associations were identified between many risk factors and AD, the low predictive accuracies suggest that specialised healthcare diagnosis data is not sufficient for predicting AD and linkage with other data sources is needed.

Pneumonia Risk, Antipsychotic Dosing, and Anticholinergic Burden in Schizophrenia

Antipsychotic drugs (particularly clozapine) have been associated with pneumonia in observational studies. Despite studies of the associations between antipsychotic use and incident pneumonia, it remains unclear to what degree antipsychotic use is associated with increased risk of pneumonia, whether dose-response associations exist, and what agents are specifically associated with incident pneumonia. To estimate pneumonia risk associated with specific antipsychotics and examine whether polytherapy, dosing, and receptor binding properties are associated with pneumonia in patients with schizophrenia. This cohort study identified patients with schizophrenia or schizoaffective disorder (hereafter, schizophrenia) aged 16 years or older from nationwide Finnish registers from 1972 to 2014. Data on diagnoses, inpatient care, and specialized outpatient care were obtained from the Hospital Discharge Register. Information on outpatient medication dispensing was obtained from the Prescription Register. Study follow-up was from 1996 to 2017. Data were analyzed from November 4, 2022, to December 5, 2023. Use of specific antipsychotic monotherapies; antipsychotics modeled by dosage as low (<0.6 of the World Health Organization defined daily dose [DDD] per day), medium (0.6 to <1.1 DDDs per day), or high dose (≥1.1 DDDs per day); antipsychotic polypharmacy; and antipsychotics categorized according to their anticholinergic burden as low, medium, and high. The primary outcome was hospitalization for incident pneumonia. Pneumonia risk was analyzed using adjusted, within-individual Cox proportional hazards regression models, with no antipsychotic use as the reference. The study included 61 889 persons with schizophrenia (mean [SD] age, 46.2 [16.0] years; 31 104 men [50.3%]). During 22 years of follow-up, 8917 patients (14.4%) had 1 or more hospitalizations for pneumonia and 1137 (12.8%) died within 30 days of admission. Compared with no antipsychotic use, any antipsychotic use overall was not associated with pneumonia (adjusted hazard ratio [AHR], 1.12; 95% CI, 0.99-1.26). Monotherapy use was associated with increased pneumonia risk compared with no antipsychotic use (AHR, 1.15 [95% CI, 1.02-1.30]; P = .03) in a dose-dependent manner, but polytherapy use was not. When categorized by anticholinergic burden, only the use of antipsychotics with a high anticholinergic burden was associated with pneumonia (AHR, 1.26 [95% CI, 1.10-1.45]; P < .001). Of specific drugs, high-dose quetiapine (AHR, 1.78 [95% CI, 1.22-2.60]; P = .003), high- and medium-dose clozapine (AHR, 1.44 [95% CI, 1.22-1.71]; P < .001 and AHR, 1.43 [95% CI, 1.18-1.74]; P < .001, respectively), and high-dose olanzapine (AHR, 1.29 [95% CI, 1.05-1.58]; P = .02) were associated with increased pneumonia risk. Results of this cohort study suggest that in patients with schizophrenia, antipsychotic agents associated with pneumonia include not only clozapine (at dosages ≥180 mg/d) but also quetiapine (≥440 mg/d) and olanzapine (≥11 mg/d). Moreover, monotherapy antipsychotics and antipsychotics with high anticholinergic burden are associated with increased pneumonia risk in a dose-dependent manner. These findings call for prevention strategies aimed at patients with schizophrenia requiring high-risk antipsychotics.

Cystic fibrosis patient characteristics and healthcare resource utilization in Finland using linked registries

BackgroundKnowledge of prevalence and epidemiology of cystic fibrosis (CF) and healthcare resource use among Finnish people with CF is incomplete. MethodsWe conducted a population-based matched cohort study using retrospective real-world data from linked Finnish national registries. Electronic healthcare data and drug purchases of 102 people with CF were analyzed between January 2015 and December 2019 (follow-up). A 5-fold control population was matched by sex, age, and place of residence. Comorbidities and medication use that occurred at any time during follow-up were assessed; annual rates of hospital service use were adjusted for follow-up. ResultsThe prevalence of CF in Finland was 1.85 per 100,000. Median age at diagnosis was 1 year, with 60 % diagnosed at age <2 years and 80 % at age <10 years. Median age at death in people with CF was 31.4 years (n < 5); no controls died. The most common comorbidities included chronic sinusitis (39.2 %), pneumonia (38.2 %), diabetes (20.6 %), and nasal polyps (18.6 %). The most purchased medications were antibiotics (99.0 %) and pancreatic enzymes (84.3 %). The annualized rate of hospital visits was higher in people with CF vs controls (outpatient: mean [SD], 17.4 [14.5] vs 0.9 [3.3]; median, 13.6 vs 0.4, respectively; inpatient: mean [SD], 1.0 [1.66] vs 0.03 [0.14]; median, 0.34 vs 0, respectively). ConclusionsThe prevalence of CF in Finland is remarkably low, likely reflecting unique population characteristics and, in part, delayed diagnosis. Antibiotic use is frequent among Finnish people with CF. Inpatient hospital visits are >30 times higher in people with CF than matched controls.