I-Jun Chou

Significance of serum uric acid levels on the risk of all-cause and cardiovascular mortality

OBJECTIVE To assess the associations between serum uric acid (SUA) level and mortality. METHODS The study included 354 110 subjects without a history of gout and whose SUA levels were tested at Chang Gung Memorial Hospital in Taiwan. Cox regression models were used to estimate hazard ratios and 95% CIs for mortality in six predefined SUA strata (≤0.17, 0.18-0.29, 0.30-0.41, 0.42-0.53, 0.54-0.65 and ≥0.66 mmol/l), after adjusting for age, sex, SUA stratum, estimated glomerular filtration rate, fasting glucose, total cholesterol and history of hypertension, diabetes mellitus, coronary heart disease, stroke, heart failure or chronic kidney disease. RESULTS There were 33 562 all-cause deaths during the study period. Crude all-cause mortality rates across the SUA strata were 52.5, 19.7, 17.4, 20.0, 28.0 and 41.1 deaths per 1000 person-years. Using the stratum 3 of SUA as a reference, the age- and sex-adjusted hazard ratios (95% CIs) across SUA strata were 2.79 (2.62, 2.96), 1.32 (1.28, 1.36), 1.00, 1.10 (1.07, 1.14), 1.42 (1.37, 1.48) and 2.12 (2.01, 2.23) for all-cause mortality; 2.24 (1.93, 2.59), 1.18 (1.10, 1.27), 1.00, 1.21 (1.14, 1.29), 1.74 (1.60, 1.88) and 2.53 (2.28, 2.81) for cardiovascular mortality and 3.41 (3.11, 3.73), 1.48 (1.42, 1.55), 1.00, 0.88 (0.84, 0.92), 0.91 (0.85, 0.98) and 1.23 (1.11, 1.36) for cancer-related mortality. CONCLUSION Individuals with SUA levels at either extremes are at higher risk for all-cause and cardiovascular mortality. SUA levels of 0.30-0.41 mmol/l were associated with the lowest mortality rate and should be regarded as optimal.

Risk of myocardial infarction among patients with gout: a nationwide population-based study

OBJECTIVE To investigate the association between gout and myocardial infarction (MI) in a representative cohort in Taiwan. METHODS Data were collected from the Taiwan National Health Insurance database. Adults >20 years of age without history of MI were included. Patients were considered to have gout if they received a diagnosis of gout requiring medical treatment. Multivariate Cox proportional hazards models were used to evaluate the risk of MI in gout patients. RESULTS Of the 704 503 patients included, 26 556 (3.8%) had gout. In total, 3718 (with gout, n = 463; without gout, n = 3255) patients had an MI, 299 (with gout, n = 35; without gout, n = 264) of whom died. The incidence of MI was 2.20 and 0.60 per 1000 patient-years in individuals with and without gout, respectively (log-rank test, P < 0.001). After adjustment for age, sex and history of diabetes mellitus, hypertension, coronary heart disease (CHD), stroke and end-stage renal disease, gout was associated with MIs [hazard ratio (HR), 1.23] and non-fatal MIs (HR, 1.26). In individuals without cardiovascular risk factors, gout was associated with MIs (HR 1.84; 95% CI 1.51, 2.24) and non-fatal MIs (HR 1.80; 95% CI 1.49, 3.95), after adjustment for age and sex. Moreover, in our study population, the HRs for MI decreased as age increased. CONCLUSION Gout is an independent risk factor for MI, and the increased risk of MI is present even in young people and those without cardiovascular risk factors.

Prevalence and incidence in patients with autoimmune rheumatic diseases: A nationwide population‐based study in Taiwan

The purpose of this study was to determine the prevalence, incidence, and mortality rates of autoimmune rheumatic diseases (ARDs) by using a population‐based database.

Sex- and age-specific incidence of autoimmune rheumatic diseases in the Chinese population: A Taiwan population-based study

OBJECTIVES The purpose of this study was to estimate the sex- and age-specific incidence rates of major autoimmune rheumatic diseases (ARDs) in Taiwan using a population longitudinal database. METHODS A health insurance database containing the records of 1,000,000 beneficiaries of Taiwan National Health Insurance from 2005 to 2009 was used. RESULTS Between 2005 and 2009, the overall incidence rate of the major ARDs was 29.8 (95% CI = 28.3-31.3) per 100,000 person-years. Among the ARDs studied, the incidence of rheumatoid arthritis (RA; per 100,000 person-years) was highest (17.2, 95% CI = 16.1-18.4) and was followed by Sjögrens syndrome (11.8, 95% CI = 10.8-12.7), systemic lupus erythematosus (SLE; 7.2, 95% CI = 6.5-8.0), systemic sclerosis (SS; 1.1, 95% CI = 0.8-1.4), vasculitis (1.0, 95% CI = 0.7-1.3), Behçet disease (0.9, 95% CI = 0.6-1.1), dermatomyositis (DM; 0.7, 95% CI = 0.5-1.0), and polymyositis (PM; 0.6, 95% CI = 0.4-0.8). Females had a higher incidence ratio than did males, but a significant female/male incidence ratio was only observed for SLE (8.5, 95% CI = 6.1-12.0), Sjögrens syndrome (6.0, 95% CI = 4.8-7.6), RA (3.0, 95% CI = 2.6-3.5), and SS (2.6, 95% CI = 1.4-4.6). CONCLUSIONS ARDs are three to four times more common among women than among men in the Chinese population of Taiwan. The incidence of RA was the highest, followed by Sjögrens syndrome and SLE, while the incidence of Behçet disease was the lowest in this study. This nationwide, population-based, longitudinal epidemiological study of ARDs in Taiwan provides data for future global comparisons and may provide clues as to the etiology of these diseases.

Hyperuricaemia and accelerated reduction in renal function.

Objectives: Hyperuricaemia has been linked to reduced renal function, and evidence indicates that it may be associated with acceleration of the decline in glomerular filtration rate (GFR) and progression of chronic kidney disease (CKD). Methods: We analysed a population of subjects who had undergone serum uric acid (SUA) and serum creatinine measurements in a hospital-based cohort. Initial and final serum creatinine measurements were used to calculate the estimated glomerular filtration rate (eGFR) and the annual decline in eGFR. Cox regression was used to investigate the relationship between SUA and CKD progression. Results: A total of 63 785 subjects were enrolled in the study during a 12-year follow-up period. The mean age at the time of initial serum creatinine measurement was 50.0 ± 14.9 years. Hyperuricaemic subjects had a significantly larger annual eGFR decline, both in absolute terms (2.5 ± 9.5 mL/min/1.73 m2 per year) and as a percentage (2.8 ± 11.6% per year), as compared to the normouricaemia group (1.3 ± 9.6 mL/min/1.73 m2 per year, 1.1 ± 11.1% per year, p < 0.001). After adjustment for age, sex, status of diabetes mellitus (DM) and hypertension, baseline eGFR, azotaemia, hypercholesterolaemia, and hyperglycaemia, hyperuricaemia was associated with a hazard ratio (HR) of 1.28 [95% confidence interval (CI) 1.23–1.33, p < 0.001] for an accelerated eGFR decline ≥ 3mL/min/1.73 m2 per year and an HR of 1.52 (95% CI 1.46–1.59) for CKD progression at the end of follow-up. Conclusion: Hyperuricaemia was associated with an accelerated decline in eGFR and higher risk of CKD progression. Therefore, renal function should be monitored closely in patients with hyperuricaemia.

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 < .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.

Anti-N-Methyl-d-Aspartate Receptor Encephalitis in Taiwan—A Comparison Between Children and Adults

BACKGROUND Since the discovery of antibodies against the N-methyl-D-aspartate receptor in 2007, anti-N-methyl-D-aspartate receptor encephalitis is increasingly recognized worldwide. We compare the clinical features of adults and children with this disorder in Taiwan. METHODS Patients admitted to Chang Gung Memorial Hospital and Chang Gung Childrens Hospital and those who were referred from other institutions because of unknown encephalitis from 2009 to 2013 were enrolled, and their clinical features were analyzed. Data on cases from a review of the literature were also included in the analysis. RESULTS Twelve patients (10 females) aged between 7 years and 28 years with anti-N-methyl-D-aspartate receptor encephalitis were identified. Six patients (50%) were <18 years old, one of whom was male and three of whom had an underlying tumor. Overall, 91.6% of the patients presented with mood, behavioral, or personality changes; 91.6% developed seizures; 100% had stereotyped movements; 83.3% had autonomic instability; and 66.7% had hypoventilation. Responses to immunotherapy were slow and variable. Overall, 63.6% of the patients had a substantial recovery after immunotherapy or removal of the tumor, and one patient experienced neurological relapses. There were no significant differences in clinical manifestations between children and adults. CONCLUSIONS Anti-N-methyl-D-aspartate receptor encephalitis is increasingly recognized in Taiwan. It is characterized by its clinical features, predominantly affects females with and/or without an ovarian tumor, and it is a potentially treatable disorder. It is important for neurologists to be familiar with the clinical presentations of the disease in children and young adults.

Antineuronal Antibodies and Infectious Pathogens in Severe Acute Pediatric Encephalitis

The pathogenesis of acute encephalitis is divided into either direct infection or by immune-mediated inflammation, but the cause is still unknown. This retrospective study aimed to screen antineuronal antibodies in children with severe acute encephalitis. Thirty-four children (22 boys and 12 girls) underwent assessments such as antineuronal antibodies survey for autoimmune encephalitis and polymerase chain reaction/viral culture and antibody assays for all commonly recognized causes of infectious encephalitis. Sixteen (47.1%) were positive for autoantibodies, including antiglutamic acid decarboxylase antibodies in 16 and voltage-gated potassium channel complex antibodies in 1. Sixteen patients (47.1%) had presumed infectious etiologies, including 6 with influenza, 6 with Mycoplasma pneumoniae, 3 with enterovirus, and 1 with herpes simplex virus. In this study, influenza and Mycoplasma pneumoniae infection are the main presumed causes of severe acute encephalitis in children, although an immune-mediated mechanism may also play a role.

Analysis of Status Epilepticus with Mycoplasma pneumoniae Encephalitis

Encephalitis is characterized clinically by fever, seizure, and an altered level of consciousness. Mycoplasma pneumoniae, a common respiratory pathogen, has been implicated as an etiology of encephalitis. The present study was designed to analyze status epilepticus associated with M. pneumoniae encephalitis in a series of children through retrospective review of cases between January 2002 and January 2008. Systematic clinical data were evaluated. Nine patients were identified: five girls and four boys, aged 4 years to 10 years. All were positive for M. pneumoniae by serology. Six of the nine children (67%) developed refractory status epilepticus. The major clinical symptoms included fever (100%) and upper respiratory symptoms (78%). The most common seizure type was primary focal with secondary generalized seizure (44%). The time of follow-up for this study ranged from 18 months to 86 months. At the end of the study period, two patients had died, seven had developed epilepsy or neurologic deficits, and none had returned to baseline. These data indicate that children with status epilepticus associated with M. pneumoniae encephalitis have high mortality and morbidity. Clinicians should be aware of the potential role of M. pneumoniae in status epilepticus.

Antinuclear antibody status and risk of death in children and adolescents

Objectives: The association between the presence of antinuclear antibodies (ANA) and mortality has been rarely reported. The present study explored the value of ANA as a predictor of overall survival in children and adolescents. Methods: Patients younger than 20 years who underwent ANA testing in Chang Gung Memorial Hospital (CGMH) from 2000 to 2008 were enrolled in this study. Mortality was ascertained by using the National Death Registry of Taiwan. Positive ANA titres were categorized as low (1:40 to 1:80), medium (1:160 to 1:320), and high (≥ 1:640). Results: A total of 13 345 subjects (6579 males, 6766 females) were enrolled during the 9-year study period. The overall prevalence of low, medium, and high ANA titres was 20.8% (n = 2774), 6.0% (n = 804), and 2.5% (n = 338), respectively. During 45 140 person-years of follow-up, 146 deaths were identified and the crude mortality rates were 3.8 and 3.0 per 1000 person-years for subjects with positive and negative ANA test results, respectively (p = 0.130). Compared with ANA-negative subjects, the adjusted hazard ratio (HR) for all-cause mortality among those with a high ANA titre was 5.18 [95% confidence interval (CI) 3.13–8.57]. A low-to-medium ANA titre was not associated with increased mortality. Among the 18 deaths in individuals with a high ANA titre, 14 were due to systemic lupus erythematosus (SLE). In comparison, five out of 34 deaths among those with low-to-medium titres of ANA and none of those with negative ANA were related to SLE. Conclusions: Children and adolescents with high ANA titres should receive greater attention and monitoring to prevent unfavourable outcomes because they have a higher mortality risk than those with negative ANA results.