Distinct and shared genetic architectures of Gestational diabetes mellitus and Type 2 Diabetes Mellitus.

Gestational diabetes mellitus (GDM) affects more than 16 million pregnancies annually worldwide and is related to an increased lifetime risk of Type 2 diabetes (T2D). The diseases are hypothesized to share a genetic predisposition, but there are few GWAS studies of GDM and none of them is sufficiently powered to assess whether any variants or biological pathways are specific to GDM. We conducted the largest genome-wide association study of GDM to date in 12,332 cases and 131,109 parous female controls in the FinnGen Study and identified 13 GDM-associated loci including 8 novel loci. Genetic features distinct from T2D were identified both at the locus and genomic scale. Our results suggest that the genetics of GDM risk falls into two distinct categories - one part conventional T2D polygenic risk and one part predominantly influencing mechanisms disrupted in pregnancy. Loci with GDM-predominant effects map to genes related to islet cells, central glucose homeostasis, steroidogenesis, and placental expression. These results pave the way for an improved biological understanding of GDM pathophysiology and its role in the development and course of T2D.

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 Jyväskylä 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 (€) 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.

Patients with rheumatic diseases share similar patterns of healthcare resource utilization.

Objectives: Healthcare service needs have changed with the use of effective treatment strategies. Using data from the modern era, we aimed to explore and compare health service-related direct costs in juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), rheumatoid arthritis (RA), and axial spondyloarthritis (AxSpA). Methods: We linked a longitudinal, population-based clinical data set from Finland's largest non-university hospital's rheumatology clinic with an administrative database on health service-related direct costs in 2014. We compared all-cause costs and costs of comorbidities between adult patients with JIA, PsA, RA, and AxSpA (including ankylosing spondylitis). We also characterized patients with high healthcare resource utilization. Results: Cost distributions were similar between rheumatic diseases (p = 0.88). In adulthood, patients with JIA displayed a similar economic burden to much older patients with other inflammatory rheumatic diseases. A minority were high utilizers: among 119 patients with JIA, 15% utilized as much as the remaining 85%. For PsA (213 patients), RA (1086), and AxSpA (277), the high-utilization proportion was 10%. Both low and high utilizers showed rather low disease activity, but in high utilizers, the patient-reported outcomes were slightly worse, with the most distinct differences in pain levels. Of health service-related direct costs, index rheumatic diseases comprised only one-third (43.6% in JIA) and the majority were comorbidity costs. Conclusions: Patients with JIA, PsA, RA, and AxSpA share similar patterns of healthcare resource utilization, with substantial comorbidity costs and a minority being high utilizers. Innovations in meeting these patients' needs are warranted.

Healthcare costs and outcomes in adult patients with juvenile idiopathic arthritis: a population-based study.

OBJECTIVES: Evidence of the economic burden and long-term outcomes of juvenile idiopathic arthritis (JIA) remains scarce. Our aim was to explore healthcare costs and long-term outcomes in adult patients with JIA. METHOD: We identified all adult patients (≥ 18 years) with JIA who visited Jyväskylä Central Hospital rheumatology unit between May 2007 and March 2016. We considered individual medians of time-dependent clinical variables. These data were linked to administrative data from the area from the fiscal year 2014, which include information on all public healthcare contacts. Healthcare utilization is presented as direct costs in euros (EUR). Factors affecting direct costs were assessed with a generalized linear model. RESULTS: In 218 patients, median 28-joint Disease Activity Score with three variables (DAS28-3) was < 2.6 in 88.6% in those aged < 30 and in 72.9% in those aged ≥ 30 years, and median Health Assessment Questionnaire (HAQ) score was < 0.5 in 85.7% and 45.4%, respectively. In the utilization data (four municipalities, 137 patients), the total annual health services-related direct costs were 432 257 EUR (mean = 3155 EUR/patient/year). Thirty-six patients (26.3%) used biological disease-modifying anti-rheumatic drugs (bDMARDs) in 2014 for a total of 355 months, and the annual cost of bDMARDs was estimated at 355 000 EUR. Those with active disease had mean costs 2.4-fold higher than those with low or no disease activity. A one-point increase in median raw HAQ incurred an average 228 EUR increase in annual costs (p = 0.03). CONCLUSION: Most adult patients with JIA seem to manage well with their arthritis, bearing in mind that there still is room for improvement in long-term outcomes.

Common variant at 16p11.2 conferring risk of psychosis.

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).

A national patient dose survey and setting of reference levels for interventional radiology in Bulgaria.

OBJECTIVES: A national study on patient dose values in interventional radiology and cardiology was performed in order to assess current practice in Bulgaria, to estimate the typical patient doses and to propose reference levels for the most common procedures. METHODS: Fifteen units and more than 1,000 cases were included. Average values of the measured parameters for three procedures-coronary angiography (CA), combined procedure (CA + PCI) and lower limb arteriography (LLA)--were compared with data published in the literature. RESULTS: Substantial variations were observed in equipment and procedure protocols used. This resulted in variations in patient dose: air-kerma area product ranges were 4-339, 6-1,003 and 0.2-288 Gy cm(2) for CA, CA + PCI and LLA respectively. Reference levels for air kerma-area product were proposed: 40 Gy cm(2) for CA, 140 Gy cm(2) for CA + PCI and 45 Gy cm(2) for LLA. Auxiliary reference intervals were proposed for other dose-related parameters: fluoroscopy time, number of images and entrance surface air kerma rate in fluoroscopy and cine mode. CONCLUSIONS: There is an apparent necessity for improvement in the classification of peripheral procedures and for standardisation of the protocols applied. It is important that patient doses are routinely recorded and compared with reference levels. KEY POINTS: • Patient doses in interventional radiology are high and vary greatly • Better standardisation of procedures and techniques is needed to improve practice • Dose reference levels for most common procedures are proposed.

Safety and indoor mobility in the elderly.

The aim of this study was to find the basis for developing and adapting the environment to support the easy and safe moving of the elderly. In the field study, the daily activities and previous falls were inquired, the performance of the elderly was examined and the safety of the residential environment was surveyed among 70-80 years old subjects (N15). The second part was performed in the laboratory. 70-80 years old subjects (N55) walked on the test track. The risk level of most houses studied was moderate. In the residential surveying, all subjects had problems to stretch to high levels and most had problems to stretch to low levels. In the laboratory, errors happened often during line walking and zigzag walking in the stick track. Unsteadiness in gait was caused by extra pieces on the track and box carrying in one third of the subjects. The old subjects estimated that stairs somewhat lower than normally recommended were easier to climb. The results indicated, that new criteria and regulations are needed for the residential environment for the elderly and that it is possible to improve the safety of indoor mobility among the elderly in many ways.

Patient dose and image quality in five standard x-ray examinations.

Patient doses and image quality in five standard x-ray examination projections (22-36 measurements per each projection) have been measured, using homogeneous phantoms. The means and range of variation for the entrance skin air kerma values were: abdomen AP 5.2 mGy (1.1-21 mGy), chest PA 0.27 mGy (0.035-0.84 mGy), lumbar spine AP 8.4 mGy (2.9-28 mGy), skull LAT 3.1 mGy (1.1-7.7 mGy), and thoracic spine AP 7.9 mGy (1.3-22 mGy). Considerable variation was found in image quality parameters: film optical densities, image contrasts, and resolutions as well as in exposure values, tube voltages, exposure times, and in half-value thicknesses. The study indicated the need to standardize medical x-ray examination techniques in different x-ray departments. The measuring method can be used for comparing the patient dose and image quality of an individual x-ray unit to the doses and image quality in general use. The results can be used as the reference values for quality control of x-ray equipment.