Effect of allopurinol on all-cause mortality in adults with incident gout: propensity score–matched landmark analysis

Objective: To examine the association between allopurinol use and all-cause mortality for patients with incident gout. Methods: We compared all-cause mortality in incident gout patients who received allopurinol for at least 6 months within the exposure window (1 year or 3 years) with those who did not, using the UK Clinical Practice Research Data-link. Landmark analysis was used to account for immortal time bias and propensity score matching was used to control for potential effects of known confounders. Results: Of 23 332 incident gout patients identified, the propensity score–matched cohorts contained 1016 patients exposed to allopurinol on the date 1 year from diagnosis (landmark date) and 1016 allopurinol non-users. Over a median follow-up period of 10 years after the landmark date, there were 437 allopurinol users and 443 allopurinol non-users who died during follow-up. Allopurinol users and non-users had similar risk for all-cause mortality (hazard ratio 0.99; 95% CI 0.87, 1.12). In the 3-year landmark analysis, 3519 allopurinol users (1280 died) were compared with 3519 non-users (1265 died). The hazard ratio for all-cause mortality was 1.01 (95% CI 0.92, 1.09). Conclusion: This propensity score–matched landmark analysis in a population of incident gout patients in the UK primary care setting found a neutral effect on the risk of all-cause mortality. Our study provides reassurance about the prescription of allopurinol for gout patients early in their disease course to prevent untoward consequences of chronic uncontrolled hyperuricaemia. However, whether higher than the commonly used dose of allopurinol could influence mortality remains to be determined

Impact of gout on the risk of atrial fibrillation

OBJECTIVES: To examine the risk of atrial fibrillation (AF) at the time of first diagnosis of gout compared with matched controls and to follow incident gout patients and their matched controls after diagnosis to compare their subsequent risk of AF. METHODS: From the UK Clinical Practice Research Data-link, 45 378 incident gout patients and 45 378 age-, sex-, practice-, registration year- and index year-matched controls were identified. Index dates were initial diagnosis date for gout patients and their matched controls. The risk of AF at diagnosis [odds ratios (ORs), using conditional logistic regression] and after the diagnosis of gout [hazard ratios (HRs), using Cox proportional models] were estimated, adjusted for BMI, smoking, alcohol consumption, ischaemic heart disease, heart failure, heart valve disease, hyperthyroidism and other comorbidities and medications. RESULTS: The prevalence of AF at index date in gout patients (male, 72.3%; mean age, 62.4 +/- 15.1 years) was 7.42% (95% CI 7.18, 7.66%) and in matched controls 2.83% (95% CI 2.67, 2.98%). The adjusted OR (95% CI) was 1.45 (1.29, 1.62). The cumulative probability of AF at 1, 2, 5 and 10 years after index date was 1.08, 2.03, 4.77 and 9.68% in gout patients and 0.43, 1.08, 2.95 and 6.33% in controls, respectively (log-rank test, P < 0.001). The adjusted HR (95% CIs) was 1.09 (1.03, 1.16). CONCLUSION: This population-based study indicates that gout is independently associated with a higher risk of AF at diagnosis and the risk is also higher after the diagnosis

Association between use of non–vitamin k oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation

Importance:  Non–vitamin K oral anticoagulants (NOACs) are commonly prescribed with other medications that share metabolic pathways that may increase major bleeding risk. Objective:  To assess the association between use of NOACs with and without concurrent medications and risk of major bleeding in patients with nonvalvular atrial fibrillation. Design, Setting, and Participants:  Retrospective cohort study using data from the Taiwan National Health Insurance database and including 91 330 patients with nonvalvular atrial fibrillation who received at least 1 NOAC prescription of dabigatran, rivaroxaban, or apixaban from January 1, 2012, through December 31, 2016, with final follow-up on December 31, 2016. Exposures:  NOAC with or without concurrent use of atorvastatin; digoxin; verapamil; diltiazem; amiodarone; fluconazole; ketoconazole, itraconazole, voriconazole, or posaconazole; cyclosporine; erythromycin or clarithromycin; dronedarone; rifampin; or phenytoin. Main Outcomes and Measures:  Major bleeding, defined as hospitalization or emergency department visit with a primary diagnosis of intracranial hemorrhage or gastrointestinal, urogenital, or other bleeding. Adjusted incidence rate differences between person-quarters (exposure time for each person during each quarter of the calendar year) of NOAC with or without concurrent medications were estimated using Poisson regression and inverse probability of treatment weighting using the propensity score. Results:  Among 91 330 patients with nonvalvular atrial fibrillation (mean age, 74.7 years [SD, 10.8]; men, 55.8%; NOAC exposure: dabigatran, 45 347 patients; rivaroxaban, 54 006 patients; and apixaban, 12 886 patients), 4770 major bleeding events occurred during 447 037 person-quarters with NOAC prescriptions. The most common medications co-prescribed with NOACs over all person-quarters were atorvastatin (27.6%), diltiazem (22.7%), digoxin (22.5%), and amiodarone (21.1%). Concurrent use of amiodarone, fluconazole, rifampin, and phenytoin with NOACs had a significant increase in adjusted incidence rates per 1000 person-years of major bleeding than NOACs alone: 38.09 for NOAC use alone vs 52.04 for amiodarone (difference, 13.94 [99% CI, 9.76-18.13]); 102.77 for NOAC use alone vs 241.92 for fluconazole (difference, 138.46 [99% CI, 80.96-195.97]); 65.66 for NOAC use alone vs 103.14 for rifampin (difference, 36.90 [99% CI, 1.59-72.22); and 56.07 for NOAC use alone vs 108.52 for phenytoin (difference, 52.31 [99% CI, 32.18-72.44]; P &lt; .01 for all comparisons). Compared with NOAC use alone, the adjusted incidence rate for major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin and was not significantly different for concurrent use of verapamil; diltiazem; cyclosporine; ketoconazole, itraconazole, voriconazole, or posaconazole; and dronedarone. Conclusions and Relevance:  Among patients taking NOACs for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin compared with the use of NOACs alone, was associated with increased risk of major bleeding. Physicians prescribing NOAC medications should consider the potential risks associated with concomitant use of other drugs

Risk of cardiovascular disease in Chinese patients with rheumatoid arthritis: a cross sectional study based on hospital medical records in 10 years

Objective: Though the risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA) has been established in Western population, little is known about the risk in Chinese people with RA. Our objective was to estimate the risk of CVD in Chinese people with RA using hospital medical records data. Methods The inpatients medical record database 2005‐2015 of Sichuan provincial people’s hospital was examined. All individuals with a primary diagnosis of RA were included as cases, and those of osteoarthritis (OA) were included as controls, which consisted of the unmatched dataset. Then, RA cases and OA controls were matched by sex and age at 1:1 ratio, forming the matched dataset. The morbidity of CVD (including ischemia heart disease (IHD), congestive heart failure (CHF), et al), stroke and arthrosclerosis were extracted from the database, so as the demographic data and comorbidities related to CVD. Multiple logistic regression analysis was used to estimate the risk of CVD in RA adjusted for demographics and comorbidities using the unmatched dataset. Sensitivity analysis was conducted 1) considering interaction terms between RA and comorbidities, and 2) using multivariable conditional logistic regression for the matched dataset. Results: The unmatched data set comprised of 1824RA cases and 1995 OA controls and the matched dataset comprised of 1022 pairs of sex and age matched RA and OA patients. RA exhibited increased odds of prevalent CVD compared with OA, and the adjusted ORs (95%CIs) for CVD, stroke, IHD, CHF, and atherosclerosis were1.86(1.42‐2.43), 1.11(0.71‐1.74), 1.47(0.97‐2.24), 2.09(1.03‐4.22), and 2.49 (1.97‐3.13), respectively, and was 2.26 (1.29‐3.96) for IHD further adjusted for interaction term. The matched dataset analysis found similar results. Conclusions: Chinese people with RA were approximated 2 times more 1 likely to have CVD, IHD, CHF and atherosclerosis compared with those with OA. The findings justified the need of further longitudinal study to establish the causal‐relationship between RA and CVD and to estimate the precise risk in this population

Accelerated Aging Experiments for Prognostics of Damage Growth in Composite Materials

Composite structures are gaining importance for use in the aerospace industry. Compared to metallic structures their behavior is less well understood. This lack of understanding may pose constraints on their use. One possible way to deal with some of the risks associated with potential failure is to perform in-situ monitoring to detect precursors of failures. Prognostic algorithms can be used to predict impending failures. They require large amounts of training data to build and tune damage model for making useful predictions. One of the key aspects is to get confirmatory feedback from data as damage progresses. These kinds of data are rarely available from actual systems. The next possible resource to collect such data is an accelerated aging platform. To that end this paper describes a fatigue cycling experiment with the goal to stress carbon-carbon composite coupons with various layups. Piezoelectric disc sensors were used to periodically interrogate the system. Analysis showed distinct differences in the signatures of growing failures between data collected at conditions. Periodic X-radiographs were taken to assess the damage ground truth. Results after signal processing showed clear trends of damage growth that were correlated to damage assessed from the X-ray images

Cure monitoring of composites with embedded piezoelectric sensors

Manufacturing of carbon fiber reinforce polymers (CFRPs) presents challenges because of uncertainty in the exact conditions of cure in the material, especially in a complex structure, and this effects the quality of the finished product. This work evaluates the use of piezoelectric sensors embedded into CFRP layups before curing to monitor the composite material during the cure cycle. These sensors were used to propagate ultrasonic waves through the structure at different stages during cure. By examining features of the changing ultrasonic signal, the corresponding changes in material properties of the composite can be observed

Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families

IMPORTANCE: Relatives of patients with systemic lupus erythematosus (SLE) appear to be at higher risk of SLE and other autoimmune diseases, but estimates of individual familial risks are largely unavailable or unreliable. Furthermore, relative contributions of genetic, shared, and unshared environmental factors to SLE susceptibility remain unclear. OBJECTIVE: To examine familial aggregation and heritability of SLE and the relative risks (RRs) of other autoimmune diseases in relatives of patients with SLE. DESIGN, SETTING, AND PARTICIPANTS: A population-based family study using the Taiwan National Health Insurance Research Database was conducted. Participants included all individuals (N = 23,658,577) registered with that database in 2010; of these, 18,283 had SLE. We identified 21,009,551 parent-child relationships, 17,168,340 full sibling pairs, and 342,066 twin pairs. Diagnoses of SLE were ascertained from March 1, 1995, to December 31, 2010, and analysis was conducted between March 1 and August 15, 2014. MAIN OUTCOMES AND MEASURES: The prevalence and RRs of SLE and other autoimmune diseases in relatives and spouses of patients with SLE as well as the relative contributions of heritability, shared, and nonshared environmental factors to SLE susceptibility. RESULTS: Among the more than 23 million participants, the RRs (95% CIs) for SLE were 315.94 (210.66-473.82) for twins of the patients, 23.68 (20.13-27.84) for siblings, 11.44 (9.74-13.43) for parents, 14.42 (12.45-16.70) for offspring, and 4.44 (2.38-8.30) for spouses without genetic similarity. The accountability for phenotypic variance of SLE was 43.9% for heritability, 25.8% for shared environmental factors, and 30.3% for nonshared environmental factors. The RRs (95% CIs) in individuals with a first-degree relative with SLE were 5.87 (4.89-7.05) for primary Sjogren syndrome, 5.40 (3.37-8.65) for systemic sclerosis, 2.95 (2.04-4.26) for myasthenia gravis, 2.77 (1.45-5.32) for idiopathic inflammatory myositis, 2.66 (2.28-3.11) for rheumatoid arthritis, 2.58 (1.16-5.72) for multiple sclerosis, 1.68 (1.22-2.32) for type 1 diabetes mellitus, 1.39 (0.66-2.91) for inflammatory bowel diseases, and 0.86 (0.43-1.71) for vasculitis. CONCLUSIONS AND RELEVANCE: The individual risks of SLE and other autoimmune diseases were increased in families that included patients with SLE. The heritability of SLE was estimated to be 43.9%. These data should be considered when counseling families with affected members

Familial risk of Sjögren's syndrome and co-aggregation of autoimmune diseases in affected families: a nationwide population study

Objective: To investigate familial aggregation of Sjögren's syndrome (SS) and the relative risks (RRs) of other autoimmune disease in relatives of patients with SS. Methods: We identified 23,658,577 beneficiaries enrolled in the Taiwan National Health Insurance system in 2010, of whom 12,754 had SS. We identified 21,009,551 parent–child relationships and 17,168,340 pairs of full siblings. The familial risks of SS and other autoimmune diseases, tetrachoric correlation, and familial transmission were estimated. Results: We identified 105 patients with SS who had an affected first-degree relative. The RR of SS was 18.99 (95% confidence interval [95% CI] 9.76–36.93) in siblings of patients with SS, 11.31 (95% CI 8.34–15.33) in offspring, and 12.46 (95% CI 9.34–16.62) in parents. Tetrachoric correlation coefficients were 0.53 (95% CI 0.41–0.65) for cotwins of affected individuals and 0.21 (95% CI 0.16–0.26) for full siblings. The familial transmission (heritability plus shared environmental contribution) was 0.54 (95% CI 0.44–0.77). In first-degree relatives of patients with SS, the RRs were 2.95 (95% CI 2.33–3.73) for rheumatoid arthritis, 6.25 (95% CI 5.15–7.58) for systemic lupus erythematosus, 2.39 (95% CI 0.77–7.41) for systemic sclerosis, 0.71 (95% CI 0.10–5.07) for idiopathic inflammatory myopathy, 1.97 (95% CI 1.29–3.02) for type 1 diabetes mellitus, 3.38 (95% CI 1.26–9.05) for multiple sclerosis, 1.67 (95% CI 0.83–3.33) for myasthenia gravis, 1.25 (95% CI 1.04–1.50) for psoriasis, 1.21 (95% CI 0.39–3.76) for inflammatory bowel disease, and 2.29 (95% CI 1.19–4.40) for vasculitis. Conclusion: The risk of SS and other autoimmune diseases is increased in relatives of patients with SS, and more than one-half of phenotypic variance in SS can be explained by familial factors