Treatment-related changes in serum neutrophil gelatinase-associated lipocalin (NGAL) in psoriatic arthritis: results from the PIPA cohort study.

OBJECTIVES: Obesity and psoriatic arthritis (PsA) have a complicated relationship. While weight alone does not cause PsA, it is suspected to cause worse symptoms. Neutrophil gelatinase-associated lipocalin (NGAL) is secreted through various cell types. Our objective was to assess the changes and trajectories in serum NGAL and clinical outcomes in patients with PsA during 12 months of anti-inflammatory treatment. METHOD: This exploratory prospective cohort study enrolled PsA patients initiating conventional synthetic or biological disease-modifying anti-rheumatic drugs (csDMARDs/bDMARDs). Clinical, biomarker, and patient-reported outcome measures were retrieved at baseline, and 4 and 12 months. Control groups at baseline were psoriasis (PsO) patients and apparently healthy controls. The serum NGAL concentration was quantified by a high-performance singleplex immunoassay. RESULTS: In total, 117 PsA patients started a csDMARD or bDMARD, and were compared indirectly at baseline with a cross-sectional sample of 20 PsO patients and 20 healthy controls. The trajectory in NGAL related to anti-inflammatory treatment for all included PsA patients showed an overall change of -11% from baseline to 12 months. Trajectories in NGAL for patients with PsA, divided into treatment groups, showed no clear trend in clinically significant decrease or increase following anti-inflammatory treatment. NGAL concentrations in the PsA group at baseline corresponded to the levels in the control groups. No correlation was found between changes in NGAL and changes in PsA outcomes. CONCLUSION: Based on these results, serum NGAL does not add any value as a biomarker in patients with peripheral PsA, either for disease activity or for monitoring.

The interplay between the impact of household's and children's education on the risk of type 2 diabetes and death among older adults: a Danish register-based cohort study.

OBJECTIVES: This study aims to assess the association of household's and children's education on the risk of type 2 diabetes (T2D) and subsequent death. STUDY DESIGN: Danish register-based cohort study. METHODS: In total, 1,021,557 adults were included at their 65th birthday between 2000 and 2018. A multistate survival model was performed to estimate the association of household's and children's education on the transition between the three states: 1) 65th birthday; 2) diagnosis of T2D; and 3) all-cause death. RESULTS: The incidence rates per 1000 person-years were 9.1 for T2D, 18.4 for death without T2D, and 45.0 for death with T2D. Compared to long household's education and children's education, long household's education combined with either short-medium children's education or no children were associated with a 1.49- (95% confidence interval [CI]: 1.44; 1.54] and 1.69-times (95% CI: 1.61;1.78) higher hazard of T2D, respectively. Short-medium household's education combined with either long children's education or no children were associated with 0.64- (95% CI: 0.62; 0.66) and 0.77-times (95% CI: 0.74; 0.79) lower hazard of T2D, respectively. Compared to long household's education and children's education, any other combination of household's and children's education was associated with higher hazards of death both without and with T2D. CONCLUSION: Older adults living in households with long education with no children or children with short-medium education had higher hazards of T2D. Households with short-medium education and no children or children with long education were associated with lower hazards of T2D. Both household's and children's education were associated with higher hazard of death without and with T2D.

25-year trends in first-time hospitalizations for Parkinson's disease and subsequent mortality: A Danish nationwide cohort study.

BACKGROUND: In most countries, incidence and mortality for Parkinson's disease (PD) have not been monitored by surveillance registries, although it could demonstrate the need for primary and tertiary prevention. OBJECTIVE: To examine 25-year trends in first-time hospitalizations for PD in Denmark and subsequent short and long-term mortality. METHODS: In a nationwide population-based cohort we identified all 34,947 individuals with a first-time hospitalization for PD from 1995 through 2019. We calculated standardized incidence rates of PD and 1-year and 5-year mortality by sex. Mortality rates were compared with a reference cohort randomly selected from the background population matched on sex, age, and index date. RESULTS: The annual standardized incidence rate of PD was relatively stable during the study period in both men and women. The incidence of PD was higher in men than in women and with the highest incidence in those aged 70-79 years. One and 5-year mortality risk after first-time hospitalization for PD was similar for men and women, and decreased by around 30% and 20%, respectively, between 1995 and 2019. The matched reference cohort had a similar decline in mortality over time. CONCLUSION: The rate of first-time hospitalization for PD was relatively stable between 1995 and 2019, whereas subsequent short and long-term mortality declined during the period as in the reference cohort.

Increased prevalence of sleep disturbance in psoriatic arthritis is associated with inflammatory and non-inflammatory measures.

OBJECTIVES: To examine the prevalence of sleep disturbances, quantified by the Pittsburgh Sleep Quality Index (PSQI), in patients with psoriatic arthritis (PsA), psoriasis (PsO) and healthy controls (HCs), explore associations between PSQI and clinical and patient-reported outcomes, and evaluate the effect of treatment on PSQI. METHOD: Patients were included from the Parker Institute's PsA patient cohort to evaluate the prevalence of sleep disturbances. Univariate and multivariate regression analyses were used to explore associations between sleep disturbance and outcome measures. Treatment effect in PsA patients was assessed with a mixed-effect model for repeated measures. RESULTS: In total, 109 PsA patients, 20 PsO patients, and 20 HCs were included. Sleep disturbances were reported by 66.1% of PsA patients, 45.0% of PsO patients, and 15.0% of HCs. Univariate regression analyses revealed statistically significant associations (p < 0.001) between PSQI and Disease Activity Score (DAS28CRP), tender points, visual analogue scale (VAS) patient global and pain, Psoriatic Arthritis Impact of Disease fatigue, Health Assessment Questionnaire (HAQ), and painDETECT score. Multivariate regression analysis demonstrated VAS patient global, VAS pain, and tender points as being independently associated with PSQI. The mixed-effect model revealed no effect of treatment. CONCLUSION: More PsA patients than PsO patients and HCs reported sleep disturbances. Sleep disturbances were associated with inflammatory and non-inflammatory measures possibly explaining the limited effect of treatment. This demonstrates the need for interdisciplinary approaches to improve the management of sleep disturbance in PsA.Trial registration: ClinicalTrials.gov (NCT02572700).

Angiogenic potential is reduced in skeletal muscle of aged women.

KEY POINTS: The risk of cardiovascular disease and associated skeletal muscle microvascular rarefaction is enhanced in women after menopause, yet knowledge about the angiogenic potential in ageing women is generally sparse. Aged healthy and sedentary women were found to present a markedly impaired capacity for proliferation of skeletal muscle derived microvascular endothelial cells compared to young women. Vascular endothelial growth factor (VEGF) levels in skeletal muscle myocytes and release of VEGF from myocytes tended to be lower in aged compared to young women. The aged women did not show a detectable increase in skeletal muscle capillarization with 8 weeks of intense aerobic cycle training. Combined, the findings indicate that aged women have a reduced potential for capillary growth in skeletal muscle which, with ageing, may lead to age-induced microvascular rarefaction. ABSTRACT: Skeletal muscle angiogenic potential was examined in cell cultures derived from aged and young women, and the effect of 8 weeks of intense cycle training on muscle capillary growth was determined in the group of aged women. Basal muscle samples were obtained from healthy sedentary aged (n = 12; 64 ± 4.2 years) and young women (n = 5; 24 ± 3.2 years) for endothelial cell and skeletal muscle myocyte isolation and experiments. In addition, the aged women completed an 8-week training intervention. Peak oxygen uptake and muscle samples for histology and protein determination were obtained before and after the training period. Before training, muscle microdialysate was collected from the aged women at rest and during exercise. In Part 1 of the experiments, growth-supplement stimulated proliferation of endothelial cells was ∼75% lower in cells from aged compared to young women (P < 0.001). There was a tendency for a lower vascular endothelial growth factor (VEGF) concentration in muscle conditioned media (P = 0.0696) and for a lower VEGF content in the myocytes (P = 0.0705) from aged compared to young women. Endothelial proliferation was found to be highly dependent on mitochondrial function. Acute exercise resulted in a modest (1.3-fold; P = 0.0073) increase in muscle interstitial VEGF protein in the aged women. In Part 2, 8 weeks of intense training did not change muscle capillarization (P ≥ 0.1502) in the aged women, but led to an increased amount of muscle VEGF (P = 0.0339). In conclusion, aged women have impaired angiogenic potential, which is associated with a compromised response both at the skeletal muscle myocyte and microvascular endothelial cell level.

The association between depressive mood and ischemic heart disease: a twin study.

OBJECTIVE: Individuals with mood disorders have increased risk of cardiovascular disease. The aims of this study were to evaluate if the risk of cardiovascular disease in individuals with mood disorder could be explained by shared genetic and early environmental factors. METHODS: We included 6714 Danish middle and old aged twins from two large population-based studies. Cox proportional hazards regression was used to perform individual-level and intra-pair analyses of the association between self-reported depression symptomatology scores and register-based diagnoses of ischemic heart disease. RESULTS: Higher depression symptomatology scores (both total, affective, and somatic) were associated with higher incidence of ischemic heart disease after multivariable adjustment in individual-level analyses. In intra-pair analyses, this association was similar but with slightly larger confidence intervals. There was no interaction with gender and no major differences between mono- or dizygotic twins. Within twin pairs, the twin scoring highest on depressive symptoms developed ischemic heart disease more often or earlier than the lower scoring twin. A sensitivity analysis including a 2-year time lag of depression symptomatology to limit the risk of reverse causality showed similar results. CONCLUSION: Genetic factors and early life environment do not seem to explain the association between depressive mood and ischemic heart disease.

Biological treatment in ankylosing spondylitis in the Nordic countries during 2010-2016: a collaboration between five biological registries.

OBJECTIVES: Large-scale observational cohorts may be used to study the effectiveness and rare side effects of biological disease-modifying anti-rheumatic drugs (bDMARDs) in ankylosing spondylitis (AS), but may be hampered by differences in baseline characteristics and disease activity across countries. We aimed to explore the research infrastructure in the five Nordic countries regarding bDMARD treatment in AS. METHOD: This observational cohort study was based on data from biological registries in Denmark (DANBIO), Sweden (SRQ/ARTIS), Finland (ROB-FIN), Norway (NOR-DMARD), and Iceland (ICEBIO). Data were collected for the years 2010-2016. Registry coverage, registry inventory (patient characteristics, disease activity measures), and national guidelines for bDMARD prescription in AS were described per country. Incident (first line) and prevalent bDMARD use per capita, country, and year were calculated. In AS patients who started first line bDMARDs during 2010-2016 (n = 4392), baseline characteristics and disease activity measures were retrieved. RESULTS: Registry coverage of bDMARD-treated patients ranged from 60% to 95%. All registries included extensive prospectively collected data at patient level. Guidelines regarding choice of first line drug and prescription patterns varied across countries. During the period 2010-2016 prevalent bDMARD use increased (p < 0.001), whereas incident use tended to decrease (p for trend < 0.004), with large national variations (e.g. 2016 incidence: Iceland 10.7/100 000, Finland 1.7/100 000). Baseline characteristics were similar regarding C-reactive protein, but differed for other variables, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (range 3.5-6.3) and Ankylosing Spondylitis Disease Activity Score (ASDAS) (2.7-3.8) (both p < 0.0001). CONCLUSION: Collaboration across the five Nordic biological registries regarding bDMARD use in AS is feasible but national differences in coverage, prescription patterns, and patient characteristics must be taken into account depending on the scientific question.

Nationwide time trends and risk factors for in-hospital falls-related major injuries.

BACKGROUND: Accidental falls during hospitalisation have a range of complications and more information is needed to improve prevention. We investigated patterns of in-hospital fall-related major injuries in the period 2000-2012 and the association between chronic conditions and in-hospital fall-related major injuries. METHODS: Using administrative databases, patients aged 65+ years with in-hospital falls causing fractures or head injuries with need for surgery or intensive observation were identified as cases and were individually matched with five controls. Joinpoint regression was used to examine time trends and conditional logistic regression was used to analyse odds ratio (OR) for in-hospital falls-related major injuries according to a range of comorbidities. RESULTS: Four thousand seven hundred and fifty-four cases were identified from 2000 to 2012 and the most common injury was femur fracture (61.55%). For individuals aged 65-74 and 75+ years, the incidence of in-hospital falls-related major injuries per 100,000 hospital days increased significantly in 2000-2012 (average annual change: 3.2%, CI: 0.6-5.8) and 2007-2012 (average annual change: 11.4%, CI: 5.7-17.5), respectively. Significantly increased OR for in-hospital fall-related major injuries were found for individuals with dementia (OR = 2.34, CI: 1.87-2.92), osteoporosis (OR = 1.68, CI: 1.43-1.99), stroke (OR = 1.63, CI: 1.41-1.88), depression (OR = 1.24, CI: 1.09-1.41), chronic obstructive pulmonary disease (OR = 1.18, CI: 1.01-1.39) and Parkinson disease (OR = 1.17, CI: 1.01-1.34). CONCLUSIONS: In-hospital falls-related major injuries increased significantly during the study period. Elderly with dementia, osteoporosis, stroke, depression, chronic obstructive pulmonary disease and Parkinson disease were associated with increased OR for in-hospital fall-related major injuries. Increased focus on patients with these comorbidities is warranted to decrease the increasing incidence in in-hospital major injuries.