The largest genome-wide association study for breast cancer in Taiwanese Han population.

PURPOSE: Breast cancer is a molecularly heterogeneous disease, and multiple genetic variants contribute to its development and prognosis. Most of previous genome-wide association studies (GWASs) and polygenic risk scores (PRSs) analyses focused on studying breast cancers of Caucasian populations, which may not be applicable to other population. Therefore, we conducted the largest breast cancer cohort of Taiwanese population to fill in the knowledge gap. METHODS: A total of 152,534 Participants recruited by China Medical University Hospital between 2003 and 2019 were filtered by several patient selection criteria and GWAS quality control steps, resulting in the inclusion of 2496 cases and 9984 controls for this study. We then conducted GWAS for all breast cancers and PRS analyses for all breast cancers and the four breast cancer subtypes, including luminal A, luminal B, basal-like, and HER2-enriched. RESULTS: The GWAS analyses identified 113 SNPs, 50 of which were novel. The PRS models for all breast cancers and the luminal A subtype showed positively correlated trends between the PRS and the risk of developing breast cancer. The odds ratios (95% confidence intervals) for the groups with the highest PRS in all breast cancers and the luminal A subtype were 5.33 (3.79-7.66) and 3.55 (2.13-6.14), respectively. CONCLUSION: In summary, we explored the association of genetic variants with breast cancer in the largest Taiwanese cohort and developed two PRS models that can predict the risk of developing any breast cancer and the luminal A subtype in Taiwanese women.

Age-specific percentile-based prostate-specific antigen cutoff values predict the risk of prostate cancer: A single hospital observation.

Background: Testing for prostate-specific antigen (PSA) is often recommended for men with a potential risk of prostate cancer (PCa) before requiring advanced examination. However, the best PSA cutoff value remains controversial. Object: We compared the predictive performance of age-specific percentile-based PSA thresholds with a conventional cutoff of >4 ng/mL for the risk of PCa. Methods: We included men who received PSA measurements between 2003 and 2017 in a medical center in Taiwan. Logistic regression modeling was used to assess the association between age-specific percentile-based PSA thresholds and PCa risk in age subgroups. We further applied C-statistic and decision curve analysis to compare the predictive performance of age-specific percentile-based PSA with that of a conventional cutoff PSA. Results: We identified 626 patients with PCa and 40 836 patients without PCa. The slope of PSA in patients >60-year-old was almost 3 times that of those <60-year-old (0.713 vs 0.259). The risk effect sizes of the 75th percentile PSA cutoff (<60-year-old: 2.19; 60-70-year-old: 4.36; >70-year-old: 5.84 ng/mL) were comparable to those observed based on the conventional cutoff in all age groups. However, the discrimination performance of the 75th percentile PSA cutoff was better than that of the conventional cutoff among patients aged <60-year-old (C-statistic, 0.783 vs. 0.729, p < 0.05). The 75th percentile cutoffs also correctly identified an additional 2 patients with PCa for every 100 patients with PSA screening at the threshold probability of 20%. Conclusions: Our data support the use of the 75th percentile PSA cutoff to facilitate individualized risk assessment, particularly for patients aged <60-year-old.

Association between coronary artery calcium and all-cause mortality: A large single-center retrospective cohort study.

OBJECTIVE: Previous studies have revealed that coronary artery calcium is related to cardiovascular diseases and mortality. However, most studies have been conducted in Western countries and have excluded patients with pre-existing heart disease. We investigated the association between coronary artery calcium (CAC) and all-cause mortality in an Asian cohort and in subgroups stratified by age, sex, smoking, obesity, diabetes, cardiovascular disease, blood pressure, and biochemical parameters. METHODS: We conducted a retrospective cohort study on 4529 health examinees who underwent multidetector computed tomography in a tertiary medical center in Taiwan between 2011 and 2016. The mean follow-up was 3.5 years. Cox regression was used to estimate the relative hazards of death. Stratified analyses were performed. RESULTS: The all-cause mortality rates were 2.94, 4.88, 17.6, and 33.1 per 1000 person-years for CAC scores of 0, 1-100, 101-400, and >400, respectively. The multivariable adjusted hazard ratios (95% confidence intervals [CIs]) for all-cause mortality were 0.95 (0.53, 1.72), 1.87 (0.89, 3.90), and 3.05 (1.46, 6.39) for CAC scores of 1-100, 101-400, and >400, respectively, relative to a CAC score of 0. Compared with CAC ≤ 400, the HRs (95% CIs) for CAC > 400 were 6.46 (2.44, 17.15) and 1.94 (1.00, 3.76) in younger and older adults, respectively, indicating that age was a moderating variable (p = 0.02). CONCLUSION: High CAC scores were associated with increased all-cause mortality. Although older adult patients had higher risks of death, the relative risk of death for patients with CAC > 400 was more prominent in people younger than 65 years.

Application of machine learning methods for the prediction of true fasting status in patients performing blood tests.

The fasting blood glucose (FBG) values extracted from electronic medical records (EMR) are assumed valid in existing research, which may cause diagnostic bias due to misclassification of fasting status. We proposed a machine learning (ML) algorithm to predict the fasting status of blood samples. This cross-sectional study was conducted using the EMR of a medical center from 2003 to 2018 and a total of 2,196,833 ontological FBGs from the outpatient service were enrolled. The theoretical true fasting status are identified by comparing the values of ontological FBG with average glucose levels derived from concomitant tested HbA1c based on multi-criteria. In addition to multiple logistic regression, we extracted 67 features to predict the fasting status by eXtreme Gradient Boosting (XGBoost). The discrimination and calibration of the prediction models were also assessed. Real-world performance was gauged by the prevalence of ineffective glucose measurement (IGM). Of the 784,340 ontologically labeled fasting samples, 77.1% were considered theoretical FBGs. The median (IQR) glucose and HbA1c level of ontological and theoretical fasting samples in patients without diabetes mellitus (DM) were 94.0 (87.0, 102.0) mg/dL and 5.6 (5.4, 5.9)%, and 92.0 (86.0, 99.0) mg/dL and 5.6 (5.4, 5.9)%, respectively. The XGBoost showed comparable calibration and AUROC of 0.887 than that of 0.868 in multiple logistic regression in the parsimonious approach and identified important predictors of glucose level, home-to-hospital distance, age, and concomitantly serum creatinine and lipid testing. The prevalence of IGM dropped from 27.8% based on ontological FBGs to 0.48% by using algorithm-verified FBGs. The proposed ML algorithm or multiple logistic regression model aids in verification of the fasting status.

Dyslipidemia and coronary artery calcium: From association to development of a risk-prediction nomogram.

BACKGROUND AND AIMS: The associations between dyslipidemia and coronary artery calcium (CAC) are controversial. We investigated their cross-sectional relationships and developed a predictive scoring system for prognostically significant coronary calcification (PSCC). METHODS AND RESULTS: This study evaluated the lipid profiles and the CAC score (CACS) measured through multidetector computed tomography (MDCT) among Taiwanese adult patients in a tertiary hospital between 2011 and 2016. Patients with CACS higher than 100 were classified as having PSCC. Dyslipidemia for each lipid component was defined based on the clinical cutoffs or the use of the lipid-lowering agents. Multivariable logistic regression was used to assess the association between dyslipidemia and PSCC and the model performance was assessed using calibration plot, discrimination, and a decision curve analysis. Of the 3586 eligible patients, 364 (10.2%) had PSCC. Increased age, male sex, higher body mass index (BMI), and higher level of triglyceride (TG) were associated with PSCC. The adjusted odds ratios (95% confidence intervals) of PSCC was 1.15 (0.90-1.47) for dyslipidemia defined by total cholesterol (TC) ≥200 mg/dL, 1.06 (0.83-1.35) for low-density-lipoprotein-cholesterol (LDL-C) ≥130 mg/dL, and 1.36 (1.06-1.75) for TG ≥ 200 mg/dL. The positive association between TG ≥ 200 mg/dL and PSCC was not modified by sex. Incorporating hypertriglyceridemia did not significantly improve the predictive performance of the base model comprising of age, sex, BMI, smoking, hypertension, diabetes, estimated glomerular filtration rate, and fasting glucose. CONCLUSIONS: Hypertriglyceridemia was significantly associated with the prevalent odds of PSCC. Our proposed predictive model may be a useful screening tool for PSCC.

Hypothyroidism risk associated with rheumatoid arthritis: A population-based retrospective cohort study.

ABSTRACT: Studies on the thyroid disease risk in patients with rheumatoid arthritis (RA) associated with comorbidities are limited. This population-based retrospective cohort study investigated the hypothyroidism risk in patients with RA and the role of comorbidities.We used Taiwan National Health Insurance Research Database to identify 16,714 RA patients newly diagnosed in 2000 to 2008 and 66,856 control persons without RA, frequency matched by sex, age, and index year. Incidence and the RA group to controls hazard ratio of hypothyroidism were estimated.The hypothyroidism incidence was 1.74-fold higher in the RA group than in controls (16.6 vs 9.52 per 10,000 person-years), with the Cox method estimated adjusted hazard ratio of 1.67 (95% confidence interval = 1.39-2.00) after controlling for covariates. Near 75% of the study population were women, with the incidence 3.6-time higher than men in both groups. The hypothyroidism incidence increased with age, from 12.1 per 1000 person-years in 20 to 39 years to 20.0 per 1000 person-years in 60+ years in RA patients, higher than that in controls (7.17 vs 10.0 per 1000 person-years, respectively by age). Each comorbidity was related to an increased incidence and higher in the RA group than in controls. Among all comorbidities, stroke exerted the greatest impact in the RA group with an adjusted hazard ratio of 3.85 (95% confidence interval = 1.24-12.0).RA patients have an increased risk of developing hypothyroidism; this risk was pronounced in women and the elderly. RA patients should be closely monitored to prevent the development of hypothyroidism.

Associations between Myocardial Diastolic Dysfunction and Cardiovascular Mortality in Chronic Kidney Disease: A Large Single-Center Cohort Study.

BACKGROUND: The clinical burden and prognostic role of diastolic dysfunction (DD), on the basis of the latest (2016) American Society of Echocardiography guidelines, remain unclear in patients with chronic kidney disease (CKD). Moreover, risk mapping of concomitant systolic dysfunction and DD to evaluate the hazard of cardiovascular (CV) mortality in patients with CKD remains unexplored. METHODS: This retrospective cohort study identified 20,257 adult patients who underwent comprehensive echocardiography between 2008 and 2016 at a tertiary medical center in central Taiwan. The patients were stratified by CKD stage, and 3-year CV mortality risk in each CKD stratum was estimated through multivariable Cox proportional-hazards modeling using left ventricular ejection fraction (LVEF) and DD grades on the basis of the 2016 American Society of Echocardiography guidelines as the main risk factors. RESULTS: Compared with patients with stages 1 and 2 CKD, those with stages 4 and 5 CKD had significantly lower left ventricular ejection fractions and more severe DD. Both left ventricular ejection fraction (<40% vs ≥60%; adjusted hazard ratio, 3.17; 95% CI, 2.54-3.97) and DD grade (severe DD vs normal diastolic function; adjusted hazard ratio, 3.33; 95% CI, 2.33-4.76) were independently associated with 3-year CV mortality in the entire study population and had comparable effect sizes. The corresponding adjusted hazard ratios further increased to 4.20 (95% CI, 2.45-7.21) and 4.54 (95% CI, 2.20-9.38) in patients with stages 4 and 5 CKD. Systolic dysfunction and DD demonstrated mutually augmentative effects on CV mortality. CONCLUSIONS: These findings suggest that the current practice of cardioprotection for patients with CKD should be prioritized at an early stage along with conventional nephroprotection.

Nonsteroidal Anti-Inflammatory Drugs Reduce Second Cancer Risk in Patients With Breast Cancer: A Nationwide Population-Based Propensity Score-Matched Cohort Study in Taiwan.

Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce mortality in patients with cancer, especially breast cancer, but their influence on second cancer risk is uncertain. This study aimed to examine whether NSAID use is associated with second cancer risk in patients with breast cancer. This population-based propensity score-matched cohort study using Taiwan's National Health Insurance Research Database enrolled patients with newly diagnosed breast cancer (n = 7356) with and without (n = 1839) NSAID therapy from 2000 to 2009. They were followed up until the diagnosis of second cancer, death, or end of 2011. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR). The NSAID cohort had a lower incidence rate of second cancer than the non-NSAID cohort (5.57 vs. 9.19 per 1,000 person-years), with an aHR of 0.63 (95% confidence interval (CI) 0.46-0.87). When compared with the non-NSAID cohort, the second cancer incidence was lower in patients taking non-cyclooxygenase 2 inhibitors (aHR 0.67, 95% CI 0.47-0.94) and in those receiving multiple NSAIDs during follow-up (aHR 0.55, 95% CI 0.37-0.84). A dose-response relationship existed in NSAID cumulative days. The findings demonstrate that NSAID use reduces second cancer risk in a dose-dependent manner in patients with primary breast cancer.

Trend and Predictors of Short-term Mortality of Adult Bacteremia at Emergency Departments: A 14-Year Cohort Study of 14 625 Patients.

BACKGROUND: Bacteremia is a life-threatening condition with a high mortality rate in critical care and emergency settings. The current study investigated the trend of mortality and developed predictive models of mortality for adults with bacteremia at emergency departments (EDs). METHODS: We conducted a retrospective cohort study of adults with bacteremia at the ED of China Medical University Hospital. Patient data were obtained from the Clinical Research Data Repository, and mortality information was obtained from the National Death Registry. We developed a new model to predict 7-day mortality in the derivation population and compared the model performance of the new model with Pitt Bacteremia Score (PBS) and Bloodstream Infection Mortality Risk Score (BSIMRS) in the validation population. RESULTS: We identified 14625 adult patients with first-time bacteremia at the ED, of whom 8.4% died within 7 days. From 2003 to 2016, both the cumulative incidence and 7-day mortality rate of bacteremia decreased significantly. The ED bacteremia mortality (ED-BM) model included PBS parameters, age, infection source, baseline steroid use, and biochemical profiles (estimated glomerular filtration rate, platelet, blood urea nitrogen, potassium, and hemoglobin) for predicting 7-day mortality. The discrimination performance of the ED-BM model (area under curve [AUC], 0.903) was significantly better than that of PBS (AUC, 0.848) or BSIMRS (AUC, 0.885). CONCLUSIONS: Although the cumulative incidence and mortality of ED bacteremia decreased, its mortality burden remains critical. The proposed ED-BM model had significantly better model performance than other scoring systems in predicting short-term mortality for adult patients with bacteremia at EDs.

Reduced Risk of Atrial Fibrillation Following Cholecystectomy: A Nationwide Population-Based Study.

Background: Gallstone disease (GD) is associated with a high risk of cardiovascular disease. However, it is unknown whether GD contributes to atrial fibrillation (AF). We aimed to investigate the association between GD and AF. Methods: We performed a population-based cohort study using data from the Taiwan National Health Insurance Research Database between 2001 and 2011. A GD cohort of 230,076 patients was compared with a control cohort consisting of an equal number of patients matched for age, sex, cardiovascular and gastrointestinal comorbidities. Results: In total, 5,992 (49.8/10,000 person-years) patients with GD and 5,804 (44.5/10,000 person-years) controls developed AF. GD increased AF risk with a hazard ratio (HR) of 1.20 [95% confidence interval (CI), 1.16-1.25]. In patients with GD but without cholecystectomy, the HR of AF reached 1.57 (95% CI = 1.50-1.63). After cholecystectomy, the HR of AF significantly decreased to 0.85 (95% CI = 0.81-0.90). Among the three age groups with GD (<45, 45-64, and ≥65 years), the adjusted HRs of AF were 1.59 (95% CI = 1.08-2.33), 1.31 (95% CI = 1.18-1.45), and 1.18 (95% CI = 1.13-1.22), respectively. Compared with patients with a CHA2DS2-VASc score equal to 0, the HRs of AF risk among total cohort patients and a score equal to 1, 2, 3, and ≥ 4 were 1.28 (95% CI = 1.15-1.43), 2.26 (95% CI = 2.00-2.56), 3.81 (95% CI = 3.35-4.34), and 5.09 (95% CI = 4.42-5.87), respectively. Conclusion: This population-based longitudinal follow-up study showed that patients with GD had an increased AF risk. Moreover, cholecystectomy was related to reduced AF risk. Cardiovascular checkups may be necessary for patients with GD, especially those who are young and have other typical risk factors.

Clinical characteristics and prediction analysis of pediatric urinary tract infections caused by gram-positive bacteria.

Gram-positive (GP) pathogens are less accounted for in pediatric urinary tract infection (UTI), and their clinical impact is underrecognized. This study aimed to identify predictors of GP uropathogens in pediatric UTI. In this 14-year retrospective cohort of pediatric patients with UTI, we classified first-time UTIs cases into those caused by GP or Gram-negative (GN) bacteria. We constructed a multivariable logistic regression model to predict GP UTI. We evaluated model performance through calibration and discrimination plots. We developed a nomogram to predict GP UTI that is clinically feasible. Of 3783 children with first-time UTI, 166 (4.4%) were infected by GP and 3617 (95.6%) by GN bacteria. Among children with GP UTI, the most common uropathogens were vancomycin-resistant Enterococcus faecalis (VRE) (27.1%), Staphylococcus saprophyticus (26.5%), and coagulase-negative Staphylococci (12.7%). Eight independent risk factors were associated with GP UTI: Age ≥ 24 months (odds ratio [OR]: 3.21), no prior antibiotic use (OR: 3.13), serum white blood cell (WBC) count < 14.4 × 103/µL (OR: 2.19), high sensitivity C-reactive protein (hsCRP) < 3.4 mg/dL (OR: 2.18), hemoglobin ≥ 11.3 g/dL (OR: 1.90), negative urine leukocyte esterase (OR: 3.19), negative urine nitrite (OR: 4.13), and urine WBC < 420/µL (OR: 2.37). The model exhibited good discrimination (C-statistic 0.879; 95% CI 0.845-0.913) and calibration performance. VR E. faecalis, the leading GP uropathogen causing pediatric UTI, requires early detection for infection control. Our model for predicting GP UTI can help clinicians detect GP uropathogens and administer antibiotic regimen early.

The risk of fibromyalgia in patients with iron deficiency anemia: a nationwide population-based cohort study.

Since iron is essential for neurotransmitter synthesis, decreased iron stores might lead to reduced production of biogenic amines which phenomenon was shown in Fibromyalgia (FM) patients. The aims are to investigate the association of iron deficiency anemia (IDA) and FM and to find the effects of different interventions. We conducted a study using the Taiwan National Health Insurance Research Database. The IDA cohort consisted of 13,381 patients with newly diagnosed IDA between 2000 and 2008. Each patient with IDA was frequency-matched with one people without IDA, by sex, age and index year. The Cox proportional hazards regression analysis was conducted to estimate the association between IDA and FM risk. The event was the occurrence of FM. The overall incidence density rate of FM in the IDA cohort was higher than in the non-IDA cohort with a multivariable Cox proportional hazards model measured adjusted hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.13-1.25). When using non-IDA group as reference, we compared with different therapies for IDA. The adjusted HRs of FM were 1.38 (95% CI = 1.30-1.47), 1.10 (95% CI = 1.03-1.16), 1.18 (95% CI = 0.98-1.43) and 0.73 (95% CI = 0.58-0.90) for IDA patient without therapy, iron supplement alone, blood transfusion alone and both iron supplement and blood transfusion respectively. Our results suggest IDA is associated with an increased risk of FM. All patients should have iron supplementation both to correct anemia and replenish body stores.

Electronic medical record-based deep data cleaning and phenotyping improve the diagnostic validity and mortality assessment of infective endocarditis: medical big data initiative of CMUH.

BACKGROUND: International Classification of Diseases (ICD) code-based claims databases are often used to study infective endocarditis (IE). However, the quality of ICD coding can influence the reliability of IE research. The impact of complementing the ICD-only approach with data extracted from electronic medical records (EMRs) has yet to be explored. METHODS: We selected the information of adult patients with discharge ICD codes for IE (ICD-9: 421, 112.81, 036.42, 098.84, 115.04, 115.14, 115.94, 424.9; ICD-10: I33, I38, I39) during 2005-2016 in China Medical University Hospital. Data extraction was conducted on the basis of the modified Duke criteria to establish a reference group comprising patients with definite or possible IE. Clinical characteristics and in-hospital mortality were compared between ICD-identified and Duke-confirmed cases. The positive predictive value (PPV) was used to quantify the IE identification performance of various phenotyping algorithms. RESULTS: A total of 593 patients with discharge ICD codes for IE were identified, only 56.7% met the modified Duke criteria. The crude in-hospital mortality for Duke-confirmed and Duke-rejected IE were 24.4% and 8.2%, respectively. The adjusted in-hospital mortality for ICD-identified IE was lower than that for Duke-confirmed IE by a difference of 5.1%. The best PPV was achieved (0.90, 95% CI 0.86-0.93) when major components of the Duke criteria (positive blood culture and vegetation) were integrated with ICD codes. CONCLUSION: Integrating EMR data can considerably improve the accuracy of ICD-only approaches in phenotyping IE, which can improve the validity of EMR-based studies and their applications, including real-time surveillance and clinical decision support.

Association between statin use and second cancer risk in breast cancer patients: a nationwide population-based cohort study.

PURPOSE: Many studies have revealed that statin therapy reduced mortality in cancer patients, especially in breast cancer, but the effect for second cancer was unclear. We, therefore, performed a comparable cohort study to determine the risk of second cancer in breast cancer patients with statin therapy. METHODS: Using claims data from Taiwan's National Health Insurance Program, this study enrolled newly diagnosed breast cancer patients from 2000 to 2007 with and without statin therapy as the statin (n = 1222) and nonstatin (n = 4888) cohorts, respectively. The nonstatin cohort was propensity score matched by cohort entry year, age, and randomly selected comorbidities. These two cohorts were followed up until the diagnosis of second cancer, death, or the end of 2011. Cox proportional hazard models were used to estimate the hazard ratios. RESULTS: The statin cohort had a lower incidence rate than the nonstatin cohort for second cancer (7.37 vs. 8.36 per 1000 person-years), although the difference was not significant (adjusted hazard ratio [aHR] 0.90, 95% confidence interval [CI] 0.65-1.26). Compared with the nonstatin cohort, the second cancer risk was significantly higher for patients taking pravastatin (aHR 2.71, 95% CI 1.19-6.19) but lower for those receiving multiple statin treatment (aHR 0.45, 95% CI 0.25-0.81) and combined lipophilic and hydrophilic type of statin (aHR 0.42, 95% CI 0.20-0.89). The risk was lower for patients receiving a cumulative defined daily dose (cDDD) of > 430 (aHR 0.41, 95% CI 0.19-0.86). CONCLUSION: This study showed that there is little association between statin use and second cancer risk in breast cancer patients.

Corrigendum to "The Epidemiology of Hip Fracture among Subjects with Pyogenic Liver Abscess (PLA): A Nationwide Population-Based Study".

[This corrects the article DOI: 10.1155/2020/5901962.].

The Epidemiology of Hip Fracture among Subjects with Pyogenic Liver Abscess (PLA): A Nationwide Population-Based Study.

Pyogenic liver abscess (PLA) is a potentially fatal disease that can stimulate prominent systemic inflammation. Osteoporotic hip fracture is a major complication of systemic inflammation. This study tried to determine the epidemiology of hip fractures among PLA patients. All subjects admitted due to PLA during 1999∼2010 were assessed, excluding the subjects with a history of high energy trauma, malignancy, and previous hip fracture. We matched the control subjects to PLA patients according to age, gender, and the coding of osteoporosis by 1 : 4 ratio. The PLA patients had a 1.17-fold risk of hip fracture than the controls (aHR = 1.17, 95% CI = 1.07-1.29) after adjusting for gender, age, and comorbidities. Considering death as the competing event of suicide, the PLA patients had 1.10-fold suicide risk (aHR = 1.10, 95% CI: 1.00-1.21) than the control subjects under the competing risks regression model. The cumulative incidence of hip fracture was higher in the PLA cohort (log-rank test, p < 0.001). When compared to the controls, the fracture risk was 18.4-fold (aHR = 18.4, 95% CI = 13.0-26.1) for the PLA patients admitted 2-3 times per year and 46.0-fold (aHR = 46.0, 95% CI = 31.2-67.8) for the PLA patients admitted ≧4 times per year. The impact of PLA is more prominent among the subjects aged <45 years (aHR = 2.81, 95% CI = 1.42-5.56). Preventive measures for hip fracture might be warranted for PLA patients.

Non-alcoholic fatty liver disease among patients with sleep disorders: a Nationwide study of Taiwan.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Studies have shown that sleep apnea is associated with NAFLD. However, studies on the association between sleep disorders in general and NAFLD are limited. We conducted a nationwide population-based longitudinal study to evaluate this potential association. METHODS: We identified patients diagnosed with sleep disorders in the years 2000 through 2005 in Taiwan using the National Health Insurance Research Database and selected an equal number of patients without sleep disorders from the same database as the comparison cohort. The patients were followed from the index date to the diagnosis of NAFLD or the end of 2013. We used Cox proportional hazards models to estimate the risk of NAFLD associated with sleep disorders. RESULTS: A total of 33,045 patients with sleep disorders were identified. The incidence of NAFLD was 14.0 per 10,000 person-year in patients with sleep disorders and 6.2 per 10,000 person-year in the comparison cohort. The adjusted hazard ratio (AHR) of NAFLD associated with sleep disorders was 1.78 (95% confidence interval [95%CI]: 1.46-2.16), and other independent risk factors included male sex (AHR = 1.31, 95%CI: 1.12-1.54), age 40-59 years (AHR = 1.49, 95%CI: 1.21-1.82), and dyslipidemia (AHR = 2.51, 95%CI: 2.08-3.04). In the subgroup analyses, both patients with (AHR = 2.24, 95%CI: 1.05-4.77) and without (AHR = 1.77, 95%CI: 1.46-2.15) sleep apnea had an increased risk of NAFLD. CONCLUSIONS: Sleep disorders are associated with NAFLD, even in patients without sleep apnea. Further studies are warranted to explore the mechanisms of the association.

Hypoglycaemic episodes increase the risk of ventricular arrhythmia and sudden cardiac arrest in patients with type 2 diabetes-A nationwide cohort study.

BACKGROUND: The impact of hypoglycaemic episode (HE) on the risk of ventricular arrhythmia (VA) and sudden cardiac arrest (SCA) remains unclear. We hypothesized that HE increases the risk of both VA and SCA and that glucose-lowering agents causing HE also increase the risk of VA/SCA in patients with type 2 diabetes (T2D). METHODS: Patients aged 20 years or older with newly diagnosed T2D were identified using the Taiwan National Health Insurance Database. HE was defined as the presentation of hypoglycaemic coma or specified/unspecified hypoglycaemia. The control group consisted of T2D patients without HE. The primary outcome was the occurrence of VA (including ventricular tachycardia and fibrillation) and SCA during the defined follow-up periods. A multivariate Cox hazards regression model was used to evaluate the hazard ratio (HR) for VA or SCA. RESULTS: A total of 54 303 patients were screened, with 1037 patients with HE assigned to the HE group and 4148 frequency-matched patients without HE constituting the control group. During a mean follow-up period of 3.3 ± 2.5 years, 29 VA/SCA events occurred. Compared with the control group, HE group had a higher incidence of VA/SCA (adjusted HR: 2.42, P = .04). Patients who had used insulin for glycaemic control showed an increased risk of VA/SCA compared with patients who did not receive insulin (adjusted HR: 3.05, P = .01). CONCLUSIONS: The HEs in patients with T2D increased the risk of VA/SCA, compared with those who did not experience HEs. Use of insulin also independently increased the risk of VA/SCA.

Risk of acute exacerbation between acetaminophen and ibuprofen in children with asthma.

BACKGROUND: Antipyretics are widely prescribed in pediatric practice. Some reports have mentioned that acetaminophen and non-steroid anti-inflammatory drugs may negatively affect asthma control by causing asthma exacerbation (AE). However, many confounding factors can also influence the risks. We assessed the impact of using acetaminophen or ibuprofen on AE in asthmatic children, especially those with strong risk factors. METHODS: We used the 2010 Taiwan National Health Insurance Research Database and identified 983 children with persistent asthma aged 1-5 years old; among them, 591 used acetaminophen alone and 392 used ibuprofen alone in 2010. Then, we analyzed the risk of AE over 52 weeks in the patients with and without severe AE in the previous year. RESULTS: The ibuprofen group had a higher risk of an emergency room (ER) visit or hospitalization for AE (odds ratio (OR) = 2.10, 95% confidence interval (CI) [1.17-3.76], P = 0.01). Among asthmatic children who had severe AE in the previous year, the risk of AE was higher in the ibuprofen group than in the acetaminophen group (OR = 3.28, 95% CI [1.30-8.29], P = 0.01), where as among those who did not, the risks of AE were similar between the acetaminophen and ibuprofen groups (OR = 1.52, 95% CI [0.71-3.25], P = 0.28). CONCLUSIONS: Among young asthmatic children, use of ibuprofen was associated with a higher risk of AE than acetaminophen, if they had severe AE with ER visit or hospitalization in the previous year. Pediatricians should use antipyretics among children with asthma after a full evaluation of the risk.