Survival and death causes of patients with giant cell arteritis in Western Norway 1972-2012: a retrospective cohort study

Background: Our objective was to determine the survival and causes of death in a large and well-characterized cohort of patients with giant cell arteritis (GCA). Methods: This is a hospital-based, retrospective, observational cohort study including patients diagnosed with GCA in Western Norway during 1972–2012. Patients were identified through computerized hospital records using the International Classification of Diseases (ICD)-coding system. Medical records were reviewed. Patients were randomly assigned population controls matched on age, sex, and geography from the Central Population Registry of Norway (CPRN). Date and cause of death were obtained from the Norwegian Cause of Death Registry (NCoDR). The survival was analyzed using Kaplan-Meier methods with the Gehan-Breslow test and the causes of death using cumulative incidence and Cox models for competing risks. Results: We identified 881 cases with a clinical diagnosis of GCA of which 792 fulfilled the American College of Rheumatology (ACR) 1990 classification criteria. Among those fulfilling the ACR criteria, 528 were also biopsy-verified. Cases were matched with 2577 population controls. A total of 490 (56%) GCA patients and 1517 (59%) controls died during the study period. We found no difference in the overall survival of GCA patients compared to controls, p = 0.413. The most frequent underlying causes of death in both groups were diseases of the circulatory system followed by cancer. GCA patients had increased risk of dying of circulatory disease (HR 1.31, 95% CI 1.13–1.51, p < 0.001) but lower risk of dying of cancer (HR 0.56, 95% CI 0.42–0.73, p < 0.001) compared to population controls. Conclusions: We found no difference in the overall survival of GCA patients compared to matched controls, but there were differences in the distribution of underlying death causes.publishedVersio

Patient-reported fatigue in patients with rheumatoid arthritis who commence biologic therapy: a longitudinal study

Aims and objectives To examine changes in patient-reported fatigue, over a twelve month period, in rheumatoid arthritis patients who commence biologic treatment, and to identify possible predictors for such changes. Background Fatigue is a burdensome symptom for patients with rheumatoid arthritis. Despite biologics being effective in reducing disease activity, patients still report fatigue. Design A longitudinal observational study. Methods A total of 48 patients were enrolled in the study. Fatigue was measured by the Fatigue Severity Scale. Independent samples T-tests were used to test gender differences, and paired samples T-tests were used to measure differences between repeated measures. Bivariate and multiple regression analyses were used to examine potential predictors for changes in fatigue, such as age, sex, Disease Activity Score 28, pain and physical and emotional well-being. Results Forty-seven patients completed the study. From baseline to 12-month follow-up, fatigue decreased significantly in both women and men. Analyses of predictors were performed step-wise, and the final model included sex and physical well-being. The results from this final step showed that female sex was the only significant predictor for changes in fatigue. Conclusion Patients commencing biologic therapy reported a significant reduction in fatigue. Female sex was a significant predictor of changes in fatigue. Relevance to clinical practice Despite improvements in pharmacological treatment, patients with rheumatoid arthritis still report fatigue. This is a multifaceted health problem encompassing personal and emotional factors in addition to the clinical factors directly connected to the disease

Candidate markers for stratification and classification in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune, inflammatory disease, characterized by synovitis in small- and medium-sized joints and, if not treated early and efficiently, joint damage, and destruction. RA is a heterogeneous disease with a plethora of treatment options. The pro-inflammatory cytokine tumor necrosis factor (TNF) plays a central role in the pathogenesis of RA, and TNF inhibitors effectively repress inflammatory activity in RA. Currently, treatment decisions are primarily based on empirics and economic considerations. However, the considerable interpatient variability in response to treatment is a challenge. Markers for a more exact patient classification and stratification are lacking. The objective of this study was to identify markers in immune cell populations that distinguish RA patients from healthy donors with an emphasis on TNF signaling. We employed mass cytometry (CyTOF) with a panel of 13 phenotyping and 10 functional markers to explore signaling in unstimulated and TNF-stimulated peripheral blood mononuclear cells from 20 newly diagnosed, untreated RA patients and 20 healthy donors. The resulting high-dimensional data were analyzed in three independent analysis pipelines, characterized by differences in both data clean-up, identification of cell subsets/clustering and statistical approaches. All three analysis pipelines identified p-p38, IkBa, p-cJun, p-NFkB, and CD86 in cells of both the innate arm (myeloid dendritic cells and classical monocytes) and the adaptive arm (memory CD4+ T cells) of the immune system as markers for differentiation between RA patients and healthy donors. Inclusion of the markers p-Akt and CD120b resulted in the correct classification of 18 of 20 RA patients and 17 of 20 healthy donors in regression modeling based on a combined model of basal and TNF-induced signal. Expression patterns in a set of functional markers and specific immune cell subsets were distinct in RA patients compared to healthy individuals. These signatures may support studies of disease pathogenesis, provide candidate markers for response, and non-response to TNF inhibitor treatment, and aid the identification of future therapeutic targets.publishedVersio

Trends in the occurrence of ischaemic heart disease over time in rheumatoid arthritis: 1821 patients from 1972 to 2017

Objective To evaluate trends of acute myocardial infarction (AMI) and ischaemic heart disease (IHD) in rheumatoid arthritis (RA) patients compared with the general population over time. Method We performed a retrospective cohort study of 1821 RA patients diagnosed from 1972 to 2013. Aggregated counts of the total population of the same county (Hordaland, Norway) and period were used for comparison. Information on AMI and IHD events was obtained from hospital patient administrative systems or cardiovascular registries. We estimated incidence rates and excess of events [standardized event ratio (SER) with 95% confidence interval (CI)] compared with the general population by Poisson regression. Results There was an average annual decline of 1.6% in age- and gender-adjusted AMI incidence rates from 1972 to 2017 (p < 0.035). The difference in events (excess events) in RA patients compared with the general population declined on average by 1.3% per year for AMI and by 2.3% for IHD from 1972 to 2014. There were no significant excess AMI (SER 1.05, 95% CI 0.82–1.35) or IHD events (SER 1.02, 95% CI 0.89–1.16) for RA patients diagnosed after 1998 compared with the general population. Conclusion Incidence rates and excess events of AMI and IHD in RA patients declined from 1972 to 2017. There were no excess AMI or IHD events in RA patients diagnosed after 1998 compared with the general population.publishedVersio

Low Serum Levels of 25-Hydroxyvitamin D Predict Hip Fracture in the Elderly: A NOREPOS Study

Background: Despite considerable interest, the relationship between circulating 25-hydroxyvitamin D and the risk of hip fracture is not fully established. Objective: The objective of the study was to study the association between serum 25-hydroxyvitamin D concentrations [s-25(OH)D] and the risk of hip fracture in Norway, a high-latitude country that has some of the highest hip fracture rates worldwide. Methods: A total of 21 774 men and women aged 65–79 years attended 4 community-based health studies during 1994–2001. Information on subsequent hip fractures was retrieved from electronic hospital discharge registers, with a maximum follow-up of 10.7 years. Using a stratified case-cohort design, s-25(OH)D was determined by HPLC-atmospheric pressure chemical ionization-mass spectrometry in stored serum samples in hip fracture cases (n = 1175; 307 men, 868 women) and in gender-stratified random samples (n = 1438). Cox proportional hazards regression adapted for the case-cohort design was performed. Results: We observed an inverse association between s-25(OH)D and hip fracture; those with s-25(OH)D in the lowest quartile (<42.2 nmol/L) had a 38% [95% confidence interval (CI) 9–74%] increased risk of hip fracture compared with the highest quartile (≥67.9 nmol/L) in a model accounting for age, gender, study center, and body mass index. The association was stronger in men than in women: hazard ratio 1.65 (95% CI 1.04–2.61) vs hazard ratio 1.25 (95% CI 0.95–1.65). Conclusion: In this prospective case-cohort study of hip fractures, the largest ever reported, we found an increased risk of hip fracture in subjects in the lowest compared with the highest quartile of serum 25-hydroxyvitamin D. In accordance with the findings of previous community-based studies, low vitamin D status was a modest risk factor for hip fracture.publishedVersio

Urban–Rural Differences in Hip Fracture Mortality: A Nationwide NOREPOS Study

Higher hip fracture incidence in urban than in rural areas has been demonstrated, but urban–rural differences in posthip fracture mortality have been less investigated, and the results are disparate. Hence, the aims of the present register‐based cohort study were to examine possible urban–rural differences in short‐ and long‐term mortality in Norwegian hip fracture patients and their potential associations with sociodemographic variables, and to investigate possible urban–rural differences in excess mortality in hip fracture patients compared with the general population. Data were provided from the NOREPOS hip fracture database, the 2001 Population and Housing Census, and the National Registry. The urbanization degree in each municipality was determined by the proportion of inhabitants living in densely populated areas (rural: 2/3). Age‐adjusted mortality rates and standardized mortality ratios were calculated for hip fracture patients living in rural, semirural, and urban municipalities. A flexible parametric model was used to estimate age‐adjusted average and time‐varying HRs by category of urbanization with the rural category as reference. Among 96,693 hip fracture patients, urban residents had higher mortality than their rural‐dwelling counterparts. The HR of mortality in urban compared with rural areas peaked during the first 1 to 2 years postfracture with a maximum HR of 1.20 (95% CI, 1.10 to 1.30) in men and 1.15 (95% CI, 1.08 to 1.21) in women. The differences were significant during approximately 5 years after fracture. Adjusting for sociodemographic variables did not substantially change the results. However, absolute 30‐day mortality was not significantly different between urban and rural residents, suggesting that health‐care quality immediately postfracture does not vary by urbanization. The novel findings of a higher long‐term mortality in urban hip fracture patients might reflect disparities in health status or lifestyle, differences in posthip fracture health care or rehabilitation, or a combination of several factors

Osteoporosis as a Risk Factor for Distal Radial Fractures. A Case-Control Study

Background: Distal radial fractures occur earlier in life than hip and spinal fractures and may be the first sign of osteoporosis. The aims of this case-control study were to compare the prevalence of osteopenia and osteoporosis between female and male patients with low-energy distal radial fractures and matched controls and to investigate whether observed differences in bone mineral density between patients and controls could be explained by potential confounders. Methods: Six hundred and sixty-four female and eighty-five male patients who sustained a distal radial fracture, and 554 female and fifty-four male controls, were included in the study. All distal radial fractures were radiographically confirmed. Bone mineral density was assessed with use of dual x-ray absorptiometry at the femoral neck, total hip (femoral neck, trochanter, and intertrochanteric area), and lumbar spine (L2-L4). A self-administered questionnaire provided information on health and lifestyle factors. Results: The prevalence of osteoporosis was 34% in female patients and 10% in female controls. The corresponding values were 17% in male patients and 13% in male controls. In the age group of fifty to fifty-nine years, 18% of female patients and 5% of female controls had osteoporosis. In the age group of sixty to sixty-nine years, the corresponding values were 25% and 7%, respectively. In adjusted conditional logistic regression analyses, osteopenia and osteoporosis were significantly associated with distal radial fractures in women. Osteoporosis was significantly associated with distal radial fractures in men. Conclusions: The prevalence of osteoporosis in patients with distal radial fractures is high compared with that in control subjects, and osteoporosis is a risk factor for distal radial fractures in both women and men. Thus, patients of both sexes with an age of fifty years or older who have a distal radial fracture should be evaluated with bone densitometry for the possible treatment of osteoporosis

Interferon gamma (IFN-γ)-mediated inflammation and the kynurenine pathway in relation to risk of hip fractures: The Hordaland Health Study

Summary The cytokine interferon gamma (IFN-γ) stimulates neopterin release and tryptophan degradation into kynurenines through the kynurenine pathway. High levels of neopterin were associated with increased hip fracture risk, as were some of the kynurenines, suggesting a role of IFN-γ-mediated inflammation in the processes leading to hip fracture. Introduction Low-grade systemic inflammation has been associated with bone loss and risk of fractures. Interferon gamma (IFN-γ) initiates macrophage release of neopterin and also stimulates degradation of tryptophan along the kynurenine pathway as part of cell-mediated immune activation. Plasma neopterin and the kynurenine/tryptophan ratio (KTR) are thus markers of IFN-γ-mediated inflammation. Risk of hip fracture was investigated in relation to markers of inflammation and metabolites in the kynurenine pathway (kynurenines). Methods Participants (71 to74 years, N = 3,311) in the community-based Hordaland Health Study (HUSK) were followed for hip fractures from enrolment (1998–2000) until 31 December 2009. Plasma C-reactive protein (CRP), neopterin, KTR, and six kynurenines were investigated as predictors of hip fracture, using Cox proportional hazards regression analyses. Results A hazard ratio (HR) of 1.9 (95 % confidence interval (CI) 1.3–2.7) for hip fracture was found in the highest compared to the lowest quartile of neopterin (p trend across quartiles <0.001). CRP and KTR were not related to hip fracture risk. Among the kynurenines, a higher risk of fracture was found in the highest compared to the lowest quartiles of anthranilic acid and 3-hydroxykynurenine. For subjects in the highest quartiles of neopterin, CRP, and KTR compared to those in no top quartiles, HR was 2.5 (95 % CI 1.6–4.0). Conclusions This may indicate a role for low-grade immune activation in the pathogenic processes leading to hip fracture

Sarcopenia in patients with hip fracture: A multicenter cross-sectional study

Background: Sarcopenia is prevalent in older persons and is a risk factor for falls, fractures, and mortality. The aim of this study was to determine a) the feasibility of determining sarcopenia in patients with acute hip fracture, b) the prevalence of sarcopenia and c) associations of sarcopenia with nutritional status and comorbidities. Methods: A multicenter cross-sectional study on sarcopenia in male and female patients with acute hip fracture. Participants were previously ambulatory and living in the community. Sarcopenia was assessed postoperatively with muscle mass estimated by anthropometry using triceps skinfold, arm circumference, height, weight and sex. Grip strength was measured by Jamar dynamometer and pre-fracture mobility was by self-report using the New Mobility Score. Results: Out of 282 patients, 202 were assessed for sarcopenia of whom 74 (37%) were diagnosed as sarcopenic. Sarcopenia was associated with age, odds ratio (OR) 1.4 per 5 years, 95% confidence interval (CI) [1.1, 1.8], ASA Physical Status Classification System score, OR 2.3 per point, 95% CI [1.3, 4.3] and number of medications at discharge, OR 1.2 per medication, 95% CI [1.0, 1.3] and inversely associated with BMI, OR 0.8, 95% CI [0.7, 0.9] and serum albumin, OR 0.9, 95% CI [0.8,1.0]. Conclusions: Thirty-seven percent of assessed subjects were diagnosed with sarcopenia. Our data demonstrates that the prevalence of sarcopenia is associated with older age, malnutrition and comorbidities. Determining sarcopenia at the bedside was feasible in postoperative hip fracture patients by using grip strength, estimation of muscle mass by anthropometry and self-reported mobility

Survival and death causes of patients with giant cell arteritis in Western Norway 1972-2012: a retrospective cohort study

Background: Our objective was to determine the survival and causes of death in a large and well-characterized cohort of patients with giant cell arteritis (GCA). Methods: This is a hospital-based, retrospective, observational cohort study including patients diagnosed with GCA in Western Norway during 1972–2012. Patients were identified through computerized hospital records using the International Classification of Diseases (ICD)-coding system. Medical records were reviewed. Patients were randomly assigned population controls matched on age, sex, and geography from the Central Population Registry of Norway (CPRN). Date and cause of death were obtained from the Norwegian Cause of Death Registry (NCoDR). The survival was analyzed using Kaplan-Meier methods with the Gehan-Breslow test and the causes of death using cumulative incidence and Cox models for competing risks. Results: We identified 881 cases with a clinical diagnosis of GCA of which 792 fulfilled the American College of Rheumatology (ACR) 1990 classification criteria. Among those fulfilling the ACR criteria, 528 were also biopsy-verified. Cases were matched with 2577 population controls. A total of 490 (56%) GCA patients and 1517 (59%) controls died during the study period. We found no difference in the overall survival of GCA patients compared to controls, p = 0.413. The most frequent underlying causes of death in both groups were diseases of the circulatory system followed by cancer. GCA patients had increased risk of dying of circulatory disease (HR 1.31, 95% CI 1.13–1.51, p < 0.001) but lower risk of dying of cancer (HR 0.56, 95% CI 0.42–0.73, p < 0.001) compared to population controls. Conclusions: We found no difference in the overall survival of GCA patients compared to matched controls, but there were differences in the distribution of underlying death causes