Healthcare Utilization in Rheumatic Diseases

Rheumatoid arthritis (RA), psoriatic arthritis (PsA), juvenile idiopathic arthritis (JIA) and axial spondyloarthritis (AxSpA; including ankylosing spondylitis) are inflammatory rheumatic diseases contributing to a substantial burden on both the patient and society. During the past couple of decades, active treatment strategies and pharmacological advancements have altered their cost structures, with scarce data existing on modern cohorts. Particularly for JIA in adulthood, the cost outcomes and clinical outcomes remain poorly documented. For these four rheumatic diseases, we set out to explore the health service-related costs, with emphasis on both costs of the index rheumatic disease and the costs of comorbidities. We investigated unmet needs by identifying disease-related factors attributable to distinct healthcare utilization patterns. We linked two population-based databases: a longitudinal clinical dataset with high diagnostic validity from the Jyväskylä Central Hospital rheumatology unit, and administrative data covering all public healthcare in the area. Collection of the clinical data took place between May 2007 and March 2016, and health service-related costs in euros (€) were available for fiscal year 2014. We studied the clinical outcomes in 218 adult JIA patients, with health service-related costs available for 119 adult patients with JIA, 213 with PsA, 1086 with RA, and 277 with AxSpA. We compared their cost distributions and high healthcare utilization patterns. Despite being heterogeneous, particularly regarding age, JIA, RA, PsA, and AxSpA shared similar patterns of healthcare resource utilization, both in terms of costs incurred by the rheumatic disease and by comorbidities. The majority of patients are doing overall well both in terms of patient-reported outcomes and health service-related costs, reflecting the effects of modern anti-rheumatic treatment. However, a tenth was recognizable as high healthcare utilizers (for JIA, 15%). Particularly pain, fatigue and disability, but also comorbidity and disease activity emerged as key factors affecting healthcare resource utilization. For all diseases, comorbidities accounted for two thirds of the total costs. This study supports the existing evidence that active treatment of rheumatic diseases has entailed good outcomes and low healthcare resource utilization for the majority. Particularly chronic pain, fatigue, and disability seem to be important areas needing attention in treatment of rheumatic diseases.Nivelreuma, nivelpsoriaasi, lastenreuma ja selkärankareuma lukeutuvat tulehduksellisiin reumasairauksiin, jotka voivat aiheuttaa merkittävää haittaa potilaiden terveydelle ja elämänlaadulle. Viimeisten vuosikymmenten aikana tapahtuneet kehitysaskeleet hoitoperiaatteissa ja lääkehoidossa ovat parantaneet sairausennustetta mutta samalla lisänneet lääkehoidon kustannuksia. Näiden potilaiden terveyspalvelujen käytön kustannuksista on kuitenkin niukasti nykyaikaista tutkimustietoa. Väitöskirjatutkimuksessa tarkasteltiin ja verrattiin näiden neljän tärkeän reumasairauden terveyspalvelujen käytön kustannuksia yhdistämällä kahdenlaisia rekisteritietoja: Keski-Suomen sairaanhoitopiirin potilastietojärjestelmän tietoja (GoTreatIT-monitorointi) reumasairauksia sairastavista potilaista vuosilta 2007-2016 ja euromääräisiä hoitotuotantotietoja perustuen terveydenhuollon hoitoilmoitusjärjestelmään, eli terveydenhuollon yhteydenottoihin ja käynteihin vuodelta 2014. Ensimmäisessä osatyössä tarkasteltiin 218 potilasta, joilla oli lapsuusiässä alkanut reumasairaus, n.s. lastenreuma. Tärkein havaintomme oli, että tarkasteluaikana 16-30-vuotiaista lastenreumaa sairastavista valtaosalla toimintakyky oli hyvä ja erittäin harvalla havaittiin työkyvyttömyyttä. Toisessa osatyössä tarkastelimme 119 aikuista lastenreumaa, 213 nivelpsoriaasia, 1086 nivelreumaa ja 277 selkärankareumaa sairastavaa potilasta. Heidän keskimääräiset palveluidenkäyttökustannuksensa olivat varsin samanlaiset ja noin yksi kymmenestä potilaasta tunnistettiin terveyspalvelujen suurkäyttäjäksi. Selkärankareumaa ja lastenreumaa sairastavat olivat keskimäärin selvästi nuorempia kuin nivelreuma- ja nivelpsoriaasipotilaat ja heidän elinaikainen kustannuskertymänsä voidaan siten olettaa suuremmaksi. Kaksi kolmasosaa terveyspalvelujen käytöstä johtui liitännäissairauksista ja etenkin suurkäyttäjillä liitännäissairauksista johtuva kustannustaakka oli merkittävä. Liitännäissairauksien lisäksi terveyspalvelujen käyttöön vaikuttivat kipu ja alentunut toimintakyky. Kolmannessa osatyössä havaittiin ryhmittelyanalyysin keinoin keskeisimmäksi hoidon kehittämistarpeeksi krooninen kipu: noin kolmasosa nivelreumapotilaista koki kroonista kipua ilman merkittävää tulehdusaktiivisuutta. Tutkimuksessa havaittiin, että terveyspalvelujen kustannustaakka oli tutkituissa reumasairauksissa varsin samankaltainen ja suurimmalla osalla potilaista terveyspalvelujen käyttöön liittyvät kustannukset ovat matalat. Pieni osa potilaista käyttää suurimman osan reumapotilaiden terveydenhuollon kokonaiskustannuksista. Tulehduksen rauhoittamisen lisäksi näiden potilaiden kohdalla tulee kiinnittää huomiota etenkin kivunhallintaan

Immune system-wide Mendelian randomization and triangulation analyses support autoimmunity as a modifiable component in dementia-causing diseases

Publisher Copyright: © 2022, The Author(s).Immune system and blood–brain barrier dysfunction are implicated in the development of Alzheimer’s and other dementia-causing diseases, but their causal role remains unknown. We performed Mendelian randomization for 1,827 immune system- and blood–brain barrier-related biomarkers and identified 127 potential causal risk factors for dementia-causing diseases. Pathway analyses linked these biomarkers to amyloid-β, tau and α-synuclein pathways and to autoimmunity-related processes. A phenome-wide analysis using Mendelian randomization-based polygenic risk score in the FinnGen study (n = 339,233) for the biomarkers indicated shared genetic background for dementias and autoimmune diseases. This association was further supported by human leukocyte antigen analyses. In inverse-probability-weighted analyses that simulate randomized controlled drug trials in observational data, anti-inflammatory methotrexate treatment reduced the incidence of Alzheimer’s disease in high-risk individuals (hazard ratio compared with no treatment, 0.64, 95% confidence interval 0.49–0.88, P = 0.005). These converging results from different lines of human research suggest that autoimmunity is a modifiable component in dementia-causing diseases.Peer reviewe

Integration of questionnaire-based risk factors improves polygenic risk scores for human coronary heart disease and type 2 diabetes

Max Tamlander et al. combine polygenic risk scores and clinical assessments to improve prediction of coronary artery disease and type 2 diabetes in European cohorts. Taken together, their results provide a useful method for preliminary cardiometabolic risk assessment in patients. Large-scale biobank initiatives and commercial repositories store genomic data collected from millions of individuals, and tools to leverage the rapidly growing pool of health and genomic data in disease prevention are needed. Here, we describe the derivation and validation of genomics-enhanced risk tools for two common cardiometabolic diseases, coronary heart disease and type 2 diabetes. Data used for our analyses include the FinnGen study (N = 309,154) and the UK Biobank project (N = 343,672). The risk tools integrate contemporary genome-wide polygenic risk scores with simple questionnaire-based risk factors, including demographic, lifestyle, medication, and comorbidity data, enabling risk calculation across resources where genome data is available. Compared to routinely used clinical risk scores for coronary heart disease and type 2 diabetes prevention, the risk tools show at least equivalent risk discrimination, improved risk reclassification (overall net reclassification improvements ranging from 3.7 [95% CI 2.8-4.6] up to 6.2 [4.6-7.8]), and capacity to be improved even further with standard lipid and blood pressure measurements. Without the need for blood tests or evaluation by a health professional, the risk tools provide a powerful yet simple method for preliminary cardiometabolic risk assessment for individuals with genome data available.Peer reviewe

Cluster analysis identifies unmet healthcare needs among patients with rheumatoid arthritis

Objective: To identify the patterns of healthcare resource utilization and unmet needs of persistent disease activity, pain, and physical disability in rheumatoid arthritis (RA) by cluster analysis. Method: Patients attending the Jyvaskyla Central Hospital rheumatology unit, Finland, were, from 2007, prospectively enrolled in a clinical database. We identified all RA patients in 2010-2014 and combined their individual-level data with well-recorded administrative data on all public healthcare contacts in fiscal year 2014. We ran agglomerative hierarchical clustering (Ward's method), with 28-joint Disease Activity Score with three variables, Health Assessment Questionnaire index, pain (visual analogue scale 0-100), and total annual health service-related direct costs (euro) as clustering variables. Results: Complete-case analysis of 939 patients derived four clusters. Cluster C1 (remission and low costs, 550 patients) comprised relatively young patients with low costs, low disease activity, and minimal disability. C2 (chronic pain, disability, and fatigue, 269 patients) included those with the highest pain and fatigue levels, and disability was fairly common. C3 (inflammation, 97 patients) had rather high mean costs and the highest average disease activity, but lower average levels of pain and less disability than C2, highlighting the impact of effective treatment. C4 (comorbidities and high costs, 23 patients) was characterized by exceptionally high costs incurred by comorbidities. Conclusions: The majority of RA patients had favourable outcomes and low costs. However, a large group of patients was distinguished by chronic pain, disability, and fatigue not unambiguously linked to disease activity. The highest healthcare costs were linked to high disease activity or comorbidities.Peer reviewe

Rintasyöpäriskin arviointiin uusia genomityökaluja

Vertaisarvioitu.Tutkimukset viimeksi kuluneen vuosikymmenen ajalta ovat osoittaneet rintasyövän perinnöllisen alttiuden monimuotoisuuden. Yksittäisten merkittävien rintasyövän alttiusgeenien mutaatioita seulotaan ja valikoitujen potilaiden osalta myös hyödynnetään, mutta testauskriteerit täyttävistäkin vain noin kuudennekselta löydetään tällainen mutaatio. Sairastumisriskin arvioimiseksi on viime vuosina kehitetty moniin tauteihin polygeenisiä riskisummia - tehokkaita algoritmeja, jotka huomioivat riskitekijöitä perimänlaajuisesti. Suuri rintasyövän polygeeninen riski lisää rintasyöpäriskiä huomattavasti ja rikastuu yksittäisten mutaatioiden tapaan sukuihin. Siksi rintasyövän geneettisen riskinarvioinnin tulisi olla nykyistä kokonaisvaltaisempaa. Polygeenisen riskiarvion lupaavimmat käyttökohteet ovat naisten, joiden rintasyöpäriski on suuri, tunnistaminen rintasyöpäpotilaiden lähisukulaisten joukosta, sekä yksittäisten merkittävien mutaatioiden kantajien riskiarvion tarkentaminen.Peer reviewe

Systematic comparison of family history and polygenic risk across 24 common diseases

Peer reviewe

Polygenic Risk Scores Predict Hypertension Onset and Cardiovascular Risk

Although genetic risk scores have been used to predict hypertension, their utility in the clinical setting remains uncertain. Our study comprised N=218 792 FinnGen participants (mean age 58 years, 56% women) and N=22 624 well-phenotyped FINRISK participants (mean age 50 years, 53% women). We used public genome-wide association data to compute polygenic risk scores (PRSs) for systolic and diastolic blood pressure (BP). Using time-to-event analysis, we then assessed (1) the association of BP PRSs with hypertension and cardiovascular disease (CVD) in FinnGen and (2) the improvement in model discrimination when combining BP PRSs with the validated 4- and 10-year clinical risk scores for hypertension and CVD in FINRISK. In FinnGen, compared with having a 20 to 80 percentile range PRS, a PRS in the highest 2.5% conferred 2.3-fold (95% CI, 2.2-2.4) risk of hypertension and 10.6 years (95% CI, 9.9-11.4) earlier hypertension onset. In subgroup analyses, this risk was only 1.6-fold (95% CI, 1.5-1.7) for late-onset hypertension (age >= 55 years) but 2.8-fold (95% CI, 2.6-2.9) for early-onset hypertension (agePeer reviewe

Clinical Conditions and Their Impact on Utility of Genetic Scores for Prediction of Acute Coronary Syndrome

Background: Acute coronary syndrome (ACS) is a clinically significant presentation of coronary heart disease. Genetic information has been proposed to improve prediction beyond well-established clinical risk factors. While polygenic scores (PS) can capture an individual's genetic risk for ACS, its prediction performance may vary in the context of diverse correlated clinical conditions. Here, we aimed to test whether clinical conditions impact the association between PS and ACS. Methods: We explored the association between 405 clinical conditions diagnosed before baseline and 9080 incident cases of ACS in 387 832 individuals from the UK Biobank. Results were replicated in 6430 incident cases of ACS in 177 876 individuals from FinnGen. Results: We identified 80 conventional (eg, stable angina pectoris and type 2 diabetes) and unconventional (eg, diaphragmatic hernia and inguinal hernia) associations with ACS. The association between PS and ACS was consistent in individuals with and without most clinical conditions. However, a diagnosis of stable angina pectoris yielded a differential association between PS and ACS. PS was associated with a significantly reduced (interaction P=2.87x10(-8)) risk for ACS in individuals with stable angina pectoris (hazard ratio, 1.163 [95% CI, 1.082-1.251]) compared with individuals without stable angina pectoris (hazard ratio, 1.531 [95% CI, 1.497-1.565]). These findings were replicated in FinnGen (interaction P=1.38x10(-6)). Conclusions: In summary, while most clinical conditions did not impact utility of PS for prediction of ACS, we found that PS was substantially less predictive of ACS in individuals with prevalent stable coronary heart disease. PS may be more appropriate for prediction of ACS in asymptomatic individuals than symptomatic individuals with clinical suspicion for coronary heart disease.Peer reviewe

Human essential hypertension : no significant association of polygenic risk scores with antihypertensive drug responses

Polygenic risk scores (PRSs) for essential hypertension, calculated from>900 genomic loci, were recently found to explain a significant fraction of hypertension heritability and complications. To investigate whether variation of hypertension PRS also captures variation of antihypertensive drug responsiveness, we calculated two different PRSs for both systolic and diastolic blood pressure: one based on the top 793 independent hypertension-associated single nucleotide polymorphisms and another based on over 1 million genome-wide variants. Using our pharmacogenomic GENRES study comprising four different antihypertensive monotherapies (n similar to 200 for all drugs), we identified a weak, but (after Bonferroni correction) statistically nonsignificant association of higher genome-wide PRSs with weaker response to a diuretic. In addition, we noticed a correlation between high genome-wide PRS and electrocardiographic left ventricular hypertrophy. Finally, using data of the Finnish arm of the LIFE study (n=346), we found that PRSs for systolic blood pressure were slightly higher in patients with drug-resistant hypertension than in those with drug-controlled hypertension (p=0.03, not significant after Bonferroni correction). In conclusion, our results indicate that patients with elevated hypertension PRSs may be predisposed to difficult-to-control hypertension and complications thereof. No general association between a high PRS and less efficient drug responsiveness was noticed.Peer reviewe

Incidence, sociodemographic factors and treatment penetration of rheumatoid arthritis and psoriatic arthritis in Norway

ABSTR A C T Objectives: To evaluate nationwide incidence, sociodemographic associations and treatment penetration of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in Norway. Methods: The study combined data from nationwide registries on the total Norwegian adult population (age > 18). From the Norwegian Patient Registry, incident RA and PsA cases during 2011-2015 were identified with records of first and second healthcare episodes listing RA/PsA diagnostic codes, and > 1 episode in an internal medicine or rheumatology unit with RA/PsA code during the two-year period after the first episode. Dispensed DMARD prescriptions were obtained from the Norwegian Prescription Database. Persons with dis-pensed DMARD prescriptions or biologic DMARDs given in hospitals > 12 months before the index date were excluded. Results: Incidence of RA/PsA in Norway was 42/26 per 100,000 person-years (55/28 among women and 28/23 among men). RA peak incidence was observed at ages 70-79 in both sexes, whereas the peak incidence of PsA occurred at ages 50-59. Age-and sex-standardized incidences of RA and PsA were lower among persons with higher education levels. Within a year from the index date, 82.4/57.4% of RA/PsA patients used synthetic DMARDs while 9.4/9.5% used biologic DMARDs. Conclusions: Register-based incidence estimates for RA and PsA in Norway are similar to other Nordic countries, but slightly higher than in previous Norwegian studies. Furthermore, we found that higher socioeconomic status was associated with lower incidence of both RA and PsA. Although conventional synthetic DMARDs were less often used in early PsA than RA, frequency of biologic DMARD prescriptions was comparable. (c) 2021 Elsevier Inc. All rights reserved.Peer reviewe