Secular Trends in the Incidence, Prevalence, and Medications for Epilepsy from 2007 to 2015 in Taiwan: A Nationwide Population-Based Study.

BACKGROUND: Patients with epilepsy have a higher mortality rate than the general population. Up-to-date estimates of epilepsy incidence, prevalence, and medication use are critical to assist policymaking. METHODS: Using the National Taiwan Insurance Research Database, the standardized incidence and prevalence of epilepsy were estimated in each calendar year from 2007 to 2015. We used the incident cases of epilepsy to analyze the change in prescribing patterns from 2007 to 2015. Joinpoint regression was used to estimate secular trends. RESULTS: From 2007 to 2015, the age- and sex-standardized incidence decreased from 0.72 (95% confidence interval [CI] 0.70-0.73) to 0.54 (95% CI 0.53-0.55) per 1,000 person-years, giving an annual percentage change (APC) of -2.73 (p < 0.05). Among patients younger than 20 years, the incidence did not change significantly. The age- and sex-standardized prevalence decreased from 6.94 (95% CI 6.90-6.98) to 6.86 (95% CI, 6.82-6.89) per 1,000 people, giving an APC of -0.31 (p < 0.05). However, the prevalence increased in the 35- to 49- and 50- to 64-year age-groups. The most common first-line anticonvulsant was phenytoin in 2007 and valproate in 2015. The use of levetiracetam, clobazam, and valproate increased during the study period, with APCs of 25.48% (95% CI 19.97-31.24), 6.41 (3.09-9.85), and 2.83 (1.51-4.16), respectively. The use of carbamazepine, phenytoin, and topiramate decreased; the APCs were -23.86% (95% CI -25.25 to -22.44), -6.61 (-8.40 to -4.79), and -4.29% (-7.87 to -0.57), respectively. CONCLUSIONS: The overall prevalence and incidence of epilepsy decreased slightly from 2007 to 2015. The prescribed first-line anticonvulsant also changed over time.

Adverse birth outcomes in adolescent and young adult female cancer survivors: a nationwide population-based study.

BACKGROUND: For female adolescent and young adult (AYA), cancer with treatments may affect their children's health. Our aim was to determine reliable risk estimates of adverse birth outcomes in AYA cancer survivors and the differential effects of treatments. METHODS: The study population of 4547 births in the AYA cancer survivor group and 45,463 in the comparison group were identified from two national databases between 2004 and 2014. Detailed maternal health conditions, such as maternal comorbidities, medication use during pregnancy and lifestyles, were adjusted in the statistical analyses. The outcomes included low birth weight, preterm labour, stillbirth, small or large for gestational age, a 5-min Apgar score <7, congenital malformation and foetal distress. RESULTS: The AYA cancer survivor group had a 9% higher risk of overall adverse birth outcomes (adjusted odds ratio, 1.09; 95% confidence interval, 1.02-1.16), especially low birth weight and preterm labour than the comparison group. The radiotherapy-only group additionally had a higher risk of foetal distress, and a 5-min Apgar score <7. CONCLUSION: AYA cancer survivors, especially those who have received radiotherapy, still have higher risks of adverse birth outcomes after adjusting for detailed maternal health conditions. Preconception counselling and additional surveillance may be warranted in this population.

Association of pregnancy outcomes in women with type 2 diabetes treated with metformin versus insulin when becoming pregnant.

BACKGROUND: Metformin use in pregnancy is controversial because metformin crosses the placenta and the safety on the fetus has not been well-established. This retrospective study aimed to compare pregnancy outcomes in women with preexisting type 2 diabetes receiving metformin or standard insulin treatment. METHODS: The cohort of this population-based study includes women of age 20-44 years with preexisting type 2 diabetes and singleton pregnancies in Taiwan between 2003 and 2014. Subjects were classified into three mutually exclusive groups according to glucose-lowering treatments received before and after becoming pregnant: insulin group, switching group (metformin to insulin), and metformin group. A generalized estimating equation model adjusted for patient age, duration of type 2 diabetes, hypertension, hyperlipidemia, retinopathy, and aspirin use was used to estimate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of adverse pregnancy outcomes. RESULTS: A total of 1166 pregnancies were identified in the insulin group (n = 222), the switching group (n = 318) and the metformin group (n = 626). The insulin group and the switching group had similar pregnancy outcomes for both the mother and fetus, including risk of primary cesarean section, pregnancy-related hypertension, preeclampsia, preterm birth (< 37 weeks), very preterm birth (< 32 weeks), low birth weight (< 2500 g), high birth weight (> 4000 g), large for gestational age, and congenital malformations. The metformin group had a lower risk of primary cesarean section (aOR = 0.57; 95% CI, 0.40-0.82) and congenital malformations (aOR, 0.51; 95% CI; 0.27-0.94) and similar risk for the other outcomes as compared with the insulin group. CONCLUSIONS: Metformin therapy was not associated with increased adverse pregnancy outcomes in women with type 2 diabetes as compared with standard insulin therapy.

Incidence and Time Course of Symptomatic Paroxysmal Supraventricular Tachycardia During Pregnancy: A Nation-Wide Database Study.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) is a common arrhythmia. However, its incidence and time course in pregnant women are unclear. This study was conducted to determine the incidence of PSVT in pregnant women by trimester. METHODS: From 2001 to 2012, all pregnant women in Taiwan were monitored for PSVT events. Women who visited the emergency department or were admitted for symptomatic PSVT were enrolled in this study, and those with congenital heart diseases were excluded. RESULTS: A total of 2,387,588 pregnancies (1,623,596 mothers) were analyzed. For the women with no previous history of a PSVT event, the incidence rates of symptomatic PSVT were 15, 33, and 60 per 100,000 pregnancies during the first, second, and third trimester, respectively. For the women with a previous history of PSVT, the incidence rates were 5625, 9525, and 11526 per 100,000 pregnancies, respectively. Most PSVT events occurred during the third trimester. CONCLUSIONS: In this Taiwanese cohort of pregnant women there was a stepwise increase in the incidence of symptomatic PSVT, which peaked during the third trimester. A past history of PSVT was associated with a higher risk of recurrence during pregnancy. We suggest that clinicians should be aware of this trend. Prompt management of PSVT events may prevent maternal and fetal complications.

Validity of cancer diagnosis in the National Health Insurance database compared with the linked National Cancer Registry in Taiwan.

PURPOSE: We aimed to evaluate the validity of cancer diagnosis in the National Health Insurance (NHI) database, which has routinely collected the health information of almost the entire Taiwanese population since 1995, compared with the Taiwan National Cancer Registry (NCR). METHODS: There were 26,542,445 active participants registered in the NHI database between 2001 and 2012. National Cancer Registry and NHI database records were compared for cancer diagnosis; date of cancer diagnosis; and 1, 2, and 5 year survival. In addition, the 10 leading causes of cancer deaths in Taiwan were analyzed. RESULTS: There were 908,986 cancer diagnoses in NCR and NHI database and 782,775 (86.1%) in both, with 53,192 (5.9%) in the NHI database only and 73,019 (8.0%) in the NCR only. The positive predictive value of the NHI database cancer diagnoses was 94% for all cancers; the positive predictive value of the 10 specific cancers ranged from 95% (lung cancer) to 82% (cervical cancer). The date of diagnosis in the NHI database was generally delayed by a median of 15 days (interquartile range 8-18) compared with the NCR. The 1, 2, and 5 year survival rates were 71.21%, 60.85%, and 47.44% using the NHI database and were 71.18%, 60.17%, and 46.09% using NCR data. CONCLUSIONS: Recording of cancer diagnoses and survival estimates based on these diagnosis codes in the NHI database are generally consistent with the NCR. Studies using NHI database data must pay careful attention to eligibility and record linkage; use of both sources is recommended.

Metformin confers risk reduction for developing hepatocellular carcinoma recurrence after liver resection.

BACKGROUND: Hepatocellular carcinoma recurrence following liver resection remains a great concern. The study aims to examine the chemopreventive effect of metformin in patients undergoing liver resection for hepatocellular carcinoma from a population-based study. METHODS: All patients registered as having hepatocellular carcinoma between January 1995 and December 2011 in a nationwide database were retrospectively analysed. Outcomes related to liver resection and the presence of diabetes mellitus were assessed. Prognosis in terms of the use of metformin was further explored, in which only patients in the long-term follow-up starting at 2 years were included for analysis. RESULTS: Patients with diabetes mellitus had a significantly poorer outcome than patients without diabetes mellitus. Among diabetes mellitus patients, metformin users had significantly better survival curves in both recurrence-free survival (P<.0001) and overall survival (P<.0001) after liver resection. The hazard ratio of metformin use in hepatocellular carcinoma patients with diabetes mellitus was 0.65 (P<.05, 95% CI=0.60-0.72) for hepatocellular carcinoma recurrence and 0.79 (P<.05, 95% CI=0.72-0.88) for overall survival after liver resection. The risk reduction in hepatocellular carcinoma recurrence after liver resection was significantly associated with a dose/duration dependent of accumulated metformin usage. CONCLUSION: Diabetes mellitus has an adverse effect on patients with hepatocellular carcinoma regardless of treatment modality. The use of metformin significantly reduces the risk of hepatocellular carcinoma recurrence and improves the overall outcome of patients after liver resection if patients survives the initial 2 years. Nonetheless, a prospective controlled study is recommended for validating the metformin use on preventing postoperative hepatocellular carcinoma recurrence.

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.

Outcomes of percutaneous coronary intervention in patients with rheumatoid arthritis and systemic lupus erythematosus: an 11-year nationwide cohort study.

OBJECTIVES: Patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have an increased risk of developing coronary atherosclerosis. However, the impact of RA and SLE on the outcomes in patients undergoing percutaneous coronary intervention (PCI) remains largely underdetermined. METHODS: Using the National Health Insurance Research Database of Taiwan, we identified 171 547 adult patients who underwent first-time PCI between 2000 and 2010. Among these patients, 525 had established RA, and 211 had SLE. The ORs of inhospital mortality and HRs of overall mortality and adverse cardiac outcomes after PCI (ie, ischaemic events, repeat revascularisation and major adverse cardiac events (MACE)) in relation to RA and SLE were estimated. RESULTS: After adjustment for potential confounders, including patient characteristics and procedural variables, RA (OR=1.73, 95% CI 1.11 to 2.68) and SLE (OR=3.81, 95% CI 2.02 to 7.16) were independent predictors of inhospital mortality. In addition, RA was independently associated with overall mortality (HR=1.55, 95% CI 1.35 to 1.79), ischaemic events (HR=1.18, 95% CI 1.01 to 1.39) and MACE (HR=1.20, 95% CI 1.07 to 1.34) during long-term follow-up, whereas SLE was independently associated with overall mortality (HR=2.20, 95% CI 1.74 to 2.78), repeat revascularisation (HR=1.27, 95% CI 1.02 to 1.58) and MACE (HR=1.47, 95% CI 1.24 to 1.75). Compared with patients without autoimmune diseases, patients with more recent SLE-related hospitalisations prior to PCI were at higher risk of inhospital mortality (p for trend <0.0001). CONCLUSIONS: This study recognises the inherent risks associated with RA and SLE in patients undergoing PCI and highlights the necessity to improve the caring and secondary prevention strategies for these high-risk patients.

Association of maternal chronic disease with risk of congenital heart disease in offspring.

BACKGROUND: Information about known risk factors for congenital heart disease is scarce. In this population-based study, we aimed to investigate the relation between maternal chronic disease and congenital heart disease in offspring. METHODS: The study cohort consisted of 1 387 650 live births from 2004 to 2010. We identified chronic disease in mothers and mild and severe forms of congenital heart disease in their offspring from Taiwan's National Health Insurance medical claims. We used multivariable logistic regression analysis to assess the associations of all cases and specific types of congenital heart disease with various maternal chronic diseases. RESULTS: For mothers with the following chronic diseases, the overall prevalence of congenital heart disease in their children was significantly higher than for mothers without these diseases: diabetes mellitus type 1 (adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 1.66-3.25), diabetes mellitus type 2 (adjusted OR 2.85, 95% CI 2.60-3.12), hypertension (adjusted OR 1.87, 95% CI 1.69-2.07), congenital heart defects (adjusted OR 3.05, 95% CI 2.45-3.80), anemia (adjusted OR 1.31, 95% CI 1.25-1.38), connective tissue disorders (adjusted OR 1.39, 95% CI 1.19-1.62), epilepsy (adjusted OR 1.37, 95% CI 1.08-1.74) and mood disorders (adjusted OR 1.25, 95% CI 1.11-1.41). The same pattern held for mild forms of congenital heart disease. A higher prevalence of severe congenital heart disease was seen only among offspring of mothers with congenital heart defects or type 2 diabetes. INTERPRETATION: The children of women with several kinds of chronic disease appear to be at risk for congenital heart disease. Preconception counselling and optimum treatment of pregnant women with chronic disease would seem prudent.

A higher incidence rate of acute coronary syndrome following radiation therapy in patients with breast cancer and a history of coronary artery diseases.

This study aims to investigate whether patients with breast cancer and a history of cardiovascular diseases (CADs) are at an increased incidence of acute coronary syndrome (ACS) after receiving radiation therapy (RT). In Taiwan, 5828 patients who had a history of CAD were newly diagnosed of breast cancer and received mastectomy between 1999 and 2009. Among these patients, 1851 also received RT. The study cohort was prospectively followed to the end of 2010 for estimating the incidence of ACS in association with exposure to RT. A Cox proportional hazard model that was adjusted for covariates was used to estimate the hazard ratio (HR) of ACS. Over the study period, the incident rates of ACS for RT and control patients were estimated at 1.51 and 1.77 per 100 person-years, respectively. Covariate-adjusted regression analysis indicated that the hazard of ACS significantly increased in RT patients at an adjusted HR of 1.48 [95% confidence interval (CI) 1.18-1.87]. Both hypertension and diabetes significantly increased the hazard of ACS in this patient cohort, with adjusted HRs of 3.31 (95% CI 1.94-5.66) and 1.50 (95% CI 1.19-1.89), respectively. This 12-year follow-up study suggested excess of ACS events in association with RT exposure in patients with breast cancer who had a higher cardiovascular risk. In consideration of the benefit associated with RT, intensive cardiac care should be given to patients with breast cancer and high cardiovascular risk.

The Trend of Inflammatory Bowel Diseases in Taiwan: A Population-Based Study.

BACKGROUND AND AIM: The purpose of this study was to estimate the sex- and age-specific incidence rates of inflammatory bowel diseases (IBD) in Taiwan. Site-specific cancer occurred in patients with IBD would be reported, too. METHODS: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. RESULTS: Between 2000 and 2010, the overall incidence rate of Crohn's disease (CD) and ulcerative colitis (UC) was 0.208 and 0.838 per 100,000 person-years. For male, the incidence rate of CD was 0.195 (95 % CI 0.113-0.276) per 100,000 persons in 2000 and increased to 0.318 (95 % CI 0.216-0.421) per 100,000 persons in 2010. For female, the incidence rate of CD was 0.092 (95 % CI 0.035-0.149) per 100,000 persons in 2000 and increased to 0.210 (95 % CI 0.128-0.293) per 100,000 persons in 2010. For male, the incidence rate of UC was 0.690 (95 % CI 0.537-0.843) per 100,000 persons in 2000 and increased to 1.351 (95 % CI, 1.140-1.562) per 100,000 persons in 2010. For female, the incidence rate of UC was 0.386 (95 % CI 0.269-0.503) per 100,000 persons in 2000 and increased to 0.858 (95 % CI 0.691-1.024) per 100,000 persons in 2010. Among the CD patients, 0.19 % had colorectal cancers (1/519). Among the UC patients, 0.24 % had colorectal cancers (5/2098). CONCLUSIONS: This nationwide population-based longitudinal epidemiological study of IBD in Taiwan provides data for future global comparisons.

Association of metformin with lower atrial fibrillation risk among patients with type 2 diabetes mellitus: a population-based dynamic cohort and in vitro studies.

BACKGROUND: Atrial fibrillation (AF), an inflammatory process involving arrhythmia, is associated with severe morbidity and mortality and commonly seen in patients with diabetes mellitus (DM). The effect of metformin, the most commonly used medication for patients with DM, on AF has not been investigated. The primary aim of this study was to examine whether metformin prevented the occurrence of AF in type 2 DM patients by analyzing a nationwide, population-based dynamic cohort. Additionally, we investigated the effect of metformin on tachycardia-induced myolysis and oxidative stress in atrial cells. METHODS: The study population included 645,710 patients with type 2 diabetes and not using other anti-diabetic medication from a subset of the Taiwan National Health Insurance Research Database. Of these patients, those who used metformin were categorized as the user group, and the remaining were classified as the non-user group. The time-dependent Cox's proportional hazard model was used to examine the effect of metformin on AF and the status of metformin use was treated as a time-dependent covariate. HL-1 atrial cells were paced with or without metformin, and then troponin and heavy-chain-myosin were measured as markers of myolysis. RESULTS: After 13 years of follow-up, 9,983 patients developed AF with an incidence rate of 1.5% (287 per 100,000 person-years). After adjusting for co-morbidities and medications, metformin independently protected the diabetic patients from new-onset AF with a hazard ratio of .81 (95% confidence interval 0.76-0.86, p < 0.0001). Metformin significantly decreased the extent of pacing-induced myolysis and the production of reactive oxygen species. CONCLUSION: Metformin use was associated with a decreased risk of AF in patients with type 2 DM who were not using other anti-diabetic medication, probably via attenuation of atrial cell tachycardia-induced myolysis and oxidative stress.

No overall increased risk of cancer in patients with rheumatoid arthritis: a nationwide dynamic cohort study in Taiwan.

The association between rheumatoid arthritis (RA) and cancer is still controversial. This study aimed to estimate cancer incidence (both overall and site-specific) among patients with RA and to determine whether their cancer risk was higher than in the general population. We used the nationwide dynamic cohort from the National Health Insurance Research Database of Taiwan and obtained a total of 30,504 patients with no history of cancer who were newly diagnosed with RA between 1996 and 2008; they were followed up until 2010. Standardized incidence ratios (SIR) by age for various types of cancer were calculated in 5-year calendar periods by 5-year age intervals (quinquinquennium) to compare elevated risk of increasing age and increased cancer rate in later calendar years in Taiwan. During 225,432 person-years of follow-up, 1,595 cancers occurred, corresponding to 7.08 per 1,000 person-years. The SIR for all cancers was 0.93 (95 % CI 0.88-0.97). Most cancers were found in the first 2 years after diagnosis of RA, but the incidence decreased afterward. A significant excess of Hodgkin's lymphoma (SIR 3.31, 95 % CI 1.24-8.81) and non-Hodgkin's lymphoma (SIR 3.18, 95 % CI 2.64-3.83) was seen among patients with RA, whereas the risk of colorectal cancer was 29 % lower than the general population. In conclusion, this study showed that patients with RA do not have increased overall risk of cancers but have higher risk of hematologic malignancies and lower risk of colorectal cancer, than the general population.

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.

Identification of vancomycin-resistant enterococci clones and inter-hospital spread during an outbreak in Taiwan.

BACKGROUND: In 2003, nosocomial infections caused by vancomycin-resistant enterococci (VRE) occurred rarely in Taiwan. Between 2003 and 2010, however, the average prevalence of vancomycin resistance among enterococci spp. increased from 2% to 16% in community hospitals and from 3% to 21% in medical centers of Taiwan. We used molecular methods to investigate the epidemiology of VRE in a tertiary teaching hospital in Taiwan. METHODS: Between February 2009 and February 2011, rectal samples and infection site specimens were collected from all inpatients in the nephrology ward after patient consent was obtained. VRE strain types were determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). RESULTS: A total of 59 vanA gene-containing VRE isolates (1 per patient) were obtained; 24 originated from rectal sample surveillance of patients who exhibited no symptoms (22 Enterococcus faecium and 2 Enterococcus faecalis), and 35 had developed infections over 3 days after admission (32 E. faecium, 2 E. faecalis, and 1 Enterococcus durans). The 59 VRE isolates demonstrated vancomycin minimum inhibitory concentrations (MICs) of ≥256 µg/m. The MIC range for linezolid, tigecycline, and daptomycin was 0.25-1.5 µg/mL, 0.032-0.25 and 1-4 µg/mL, respectively. For 56 isolates, the MIC for teicoplanin was >8 µg/mL. The predominant types in the nephrology ward were MLST types 414, 78, and18 as well as PFGE types A, C, and D. CONCLUSION: VREs are endemic in nephrology wards. MLST 414 is the most predominant strain. The increase VRE prevalence is due to cross-transmission of VRE clones ST 414,78,18 by undetected VRE carriers. Because similar VRE STs had been reported in a different hospital of Taiwan, this finding may indicate inter-hospital VRE spread in Taiwan. Active surveillance and effective infection control policies are important controlling the spread of VRE in high risk hospital zones. All endemic VRE strains are resistant to teicoplanin but are sensitive to daptomycin, linezolid, and tigecycline.

The effect of paternal psoriasis on neonatal outcomes: a nationwide population-based study.

Background: Psoriasis is a chronic autoimmune disease involving both environmental and genetic risk factors. Maternal psoriasis often results in poor pregnancies that influence both mothers and newborns. However, the influence of paternal psoriasis on the newborn remains unknown. The aim of this study was to investigate whether paternal psoriasis is associated with increased risk of adverse neonatal outcomes, within a nationwide population-based data setting. Methods: Singleton pregnancies were identified in the Taiwan National Health Insurance database and National Birth Registry between 2004-2011 and classified into four study groups according to whether mothers and spouses had psoriasis (paternal(-)/maternal(-), paternal(+)/maternal(-), paternal(-)/maternal(+), and paternal(+)/maternal(+)). Data were analyzed retrospectively. Adjusted odds ratios (aOR) or hazard ratios (aHR) were calculated to evaluate the risk of neonatal outcomes between groups. Results: A total of 1,498,892 singleton pregnancies were recruited. Newborns of fathers with psoriasis but not of mothers with psoriasis were associated with an aHR (95% CI) of 3.69 (1.65-8.26) for psoriasis, 1.13 (1.06-1.21) for atopic dermatitis and 1.05 (1.01-1.10) for allergic rhinitis. Newborns of mothers with psoriasis but not of fathers with psoriasis were associated with an aOR (95% CI) of 1.26 (1.12-1.43) for low birth weight (<2500 g) and 1.64 (1.10-2.43) for low Apgar scores, and an aHR of 5.70 (2.71-11.99) for psoriasis. Conclusion: Newborns of fathers with psoriasis are associated with significantly higher risk of developing atopic dermatitis, allergic rhinitis and psoriasis. Caution is advised for adverse neonatal outcomes when either or both parents have psoriasis.

Fetal-neonatal and maternal pregnancy outcomes in women with rheumatoid arthritis: a population-based cohort study.

OBJECTIVES: Rheumatoid arthritis (RA) may adversely influence pregnancy and lead to adverse birth outcomes. This study estimated the risk of adverse fetal-neonatal and maternal pregnancy outcomes in women with RA. DESIGN: This was a retrospective cohort study. SETTING: We used both the National Health Insurance database and the Taiwan Birth Reporting System, between 2004 and 2014. PARTICIPANTS: We identified 2 100 143 singleton pregnancies with 922 RA pregnancies, either live births or stillbirths, delivered by 1 468 318 women. OUTCOME MEASURES: ORs with 95% CIs for fetal-neonatal and maternal outcomes were compared between pregnancies involving mothers with and without RA using an adjusted generalised estimating equation model. RESULTS: Covariates including age, infant sex, Charlson Comorbidity Index, urbanisation, income, occupation, birth year and maternal nationality were adjusted. Compared with pregnancies in women without RA, pregnancies in women with RA showed that the fetuses/neonates had adjusted ORs (95% CI) of 2.03 (1.66 to 2.50) for low birth weight (n=123), 1.99 (1.64 to 2.40) for prematurity (n=141), 1.77 (1.46 to 2.15) for small for gestational age (n=144) and 1.35 (1.03 to 1.78) for fetal distress (n=60). Pregnancies in women with RA had adjusted ORs (95% CI) of 1.24 (1.00 to 1.52) for antepartum haemorrhage (n=106), 1.32 (1.15 to 1.51) for caesarean delivery (n=398), and 3.33 (1.07 to 10.34) for disseminated intravascular coagulation (n=3), compared with women without RA. Fetuses/neonates born to mothers with RA did not have a higher risk of being stillborn or having fetal abnormalities. Pregnant women with RA did not have increased risks of postpartum death, cardiovascular complications, surgical complications or systemic organ dysfunction. CONCLUSIONS: Pregnancies in women with RA were associated with higher risks of multiple adverse fetal-neonatal and maternal outcomes; however, most pregnancies in these women were successful.

Adverse pregnancy outcomes in women with Behçet's disease: population-based registry linkage study in Taiwan.

OBJECTIVES: To estimate the risks of adverse pregnancy outcomes in women with Behçet's disease (BD) METHODS: Data collected by the Taiwan National Health Insurance Administration between 2001 and 2012 was used for our study. A total of 2,350,339 pregnancies from the Taiwan National Health Insurance database and birth registry were identified. Maternal history of BD in women was ascertained. A comparison was made to determine whether BD increased the risk of health issues associated with pregnancy and fetal outcomes. Using an adjusted generalized estimating equation model, we estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for fetal-neonatal and maternal outcomes. RESULTS: There were 99 pregnancies in women with BD and 2,350,240 pregnancies in women without BD. The OR and 95% CI of puerperal cerebrovascular disorders were 12.08 (1.7-85.9), and those of gestational diabetes were 1.89 (1.1-3.25). Both were higher than the values in general pregnant women after adjusting for age, infant sex, urban residence, income, occupation, birth year, and Charlson Comorbidity Index. However, there were no adverse fetal outcomes in pregnant women with BD. CONCLUSIONS: Patients with BD have no significant risks of multiple complications except for puerperal cerebrovascular disease and gestational diabetes during pregnancy. Close monitoring of blood sugar is suggested. Furthermore, neonatal outcomes were not influenced by BD. Key Points • Patients with Behçet's disease are at a risk of puerperal cerebrovascular disease and gestational diabetes during pregnancy. • The odds ratio and 95% confidence interval for puerperal cerebrovascular disorders were 12.08 (1.7-85.9), and those for gestational diabetes were 1.89 (1.1-3.25). • Pregnant patients with Behçet's disease have no risks of neonatal outcomes.