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Objective  This study aimed to determine whether neonatal hyperbilirubinemia is associated with a risk of autism spectrum disorder (ASD) using a large population-based cohort. Study Design  This retrospective cohort study used data from the children's database (2000–2012) of the National Health Insurance Research Database (1996–2012) in Taiwan. We included neonates who were born between 2000 and 2004 and aged <1 month diagnosed with and without hyperbilirubinemia. The primary outcome was physician-diagnosed ASD. At the end of 2012, multivariate Cox's regression analysis was used to estimate hazard ratios (HRs). Results  A total of 67,017 neonates were included. The neonates with hyperbilirubinemia were associated with 1.28-fold increased risk of ASD (HR = 1.28, 95% confidence interval [CI]: 1.05–1.57) compared with those without hyperbilirubinemia. In subanalysis to determine how phototherapy and exchange transfusion treatment for hyperbilirubinemia were associated with ASD showed no association between treatment and ASD, suggesting the lack of a dose-response effect of hyperbilirubinemia on the risk of ASD. Boys had a nearly six-fold higher risk of ASD than girls (HR = 5.89, 95% CI: 4.41–7.86). Additionally, neonates born with preterm birth and low birth weight were associated with a risk of ASD (HR = 1.46, 95% CI: 1.00–2.13). Conclusion  We did not observe a dose-response effect of hyperbilirubinemia on ASD, but neonatal hyperbilirubinemia may be an independent risk factor for ASD if there is a residual confounding by other perinatal complications. Therefore, this study does not support a causal link between neonatal hyperbilirubinemia exposure and the risk of ASD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Few studies have evaluated whether people infected with human immunodeficiency virus (HIV) are at an increased risk of stroke in an Asian population. We investigated the association between HIV infection and the risk of developing stroke by age, calendar year of HIV diagnosis, and follow-up duration in Taiwan. Methods: Using the claims data of a universal health insurance program, we identified 5,961 patients with HIV and 23,844 matched non-HIV subjects without previous stroke from 1998 to 2005 and followed them up until the end of 2011 to measure the incidence of stroke. Cox proportional hazards models adjusted for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (CI), with the non-HIV group as reference. Results: During a median follow-up of 8 years, the incidence rates for total, ischemic, and hemorrhagic stroke per 1000 person-years were 2.12, 1.22, and 0.60, respectively, in patients with HIV infection, and 1.98, 1.14, and 0.54, respectively, in the comparison group. HIV infection was associated with an elevated risk of developing total stroke (adjusted HR [95% CI], 1.57 [1.15–2.14]) and ischemic stroke (1.91 [1.25–2.91]) in patients aged less than 45 years, but no association was observed in other age groups (P for interaction with age, p = 0.048 and 0.024, respectively). Patients diagnosed with HIV infection in 1998–1999 had a greater HR for total stroke and ischemic stroke than those diagnosed in 2000–2002 and 2003–2005 (P for interaction, for total stroke p = 0.034, for ischemic stroke p = 0.056). The HRs did not differ by follow-up duration. Conclusions: HIV infection among a young age group is associated with increased risk of developing overall and ischemic stroke. The findings highlight the importance of screening and correcting risk factors for young stroke prevention immediately and aggressively. [ABSTRACT FROM AUTHOR]

Studies evaluating the risk of peripheral arterial disease (PAD) in patients with abdominal aortic aneurysm (AAA) are limited. We used insurance claims data of Taiwan to establish a cohort of 6590 patients with AAA newly diagnosed from 2000 to 2008 and 6590 controls without AAA matched by propensity score. The subsequent incidence density rates of PAD were estimated in both cohorts by the end of 2011, and the AAA cohort to the non-AAA cohort hazard ratios (HRs) of PAD were calculated using Cox proportional hazards models. The incidence density of PAD in the AAA cohort was 3.7-fold greater than that in the non-AAA cohort (14.1 vs 3.66 per 1000 person-years) with an adjusted HR of 3.56 (95% confidence interval [CI] = 2.89-4.39). For those without comorbidities, PAD in the AAA cohort was 7.4-fold greater than that in the non-AAA cohort (12.0 vs 1.61 per 1000 person-years) with an adjusted HR of 6.70 (95% CI = 4.43-10.1). The incidence of PAD in patients with ruptured AAA was lower than that in patients without rupture (6.95 vs 15.0 per 1000 person-years). This study demonstrates that patients with AAA are at increased risk of developing PAD. [ABSTRACT FROM AUTHOR]

Background: The etiology of herniated intervertebral disc (HIVD) disease in children and adolescents is multifactorial and not merely related to disc degeneration. Therefore, in the present study, we investigated the relationship between young asthma patients and the risk of early HIVD disease in a population under 30 years of age.Methods: Data from the National Health Insurance Research Database (NHIRD) of Taiwan were used to conduct a retrospective longitudinal cohort study. The study cohort comprised 23,470 patients with asthma (asthma group) and 23,470 patients without asthma (non-asthma group), who were selected through frequency matching on the basis of sex, age, and the index year. The study patients were followed until HIVD disease occurrence, withdrawal from the National Health Insurance program, or 31 December 2013. Cox proportional hazards regression analysis was conducted to assess the risk of HIVD disease in the asthma group after adjustment for sex, age, and comorbidities.Results: After adjustment for sex, age, and comorbidities, the asthma group had a 1.69-fold (95% confidence interval [CI] = 1.29-2.23) higher risk of HIVD disease than did the non-asthma group. In addition, the asthma group had a higher risk of cervical and lumbar HIVD diseases than did the non-asthma group (adjusted hazard ratio [HR] = 2.38; 95% CI = 1.25-4.57 and adjusted HR = 1.56; 95% CI = 1.15-2.12, respectively).Conclusions: Young patients with asthma are at a significantly higher risk of early cervical or lumbar HIVD disease. [ABSTRACT FROM AUTHOR]

The prevalence of myopia has rapidly increased in recent decades and has led to a considerable global public health concern. In this study, we elucidate the relationship between Kawasaki disease (KD) and the incidence of myopia. We used Taiwan’s National Health Insurance Research Database to conduct a population-based cohort study. We identified patients diagnosed with KD and individuals without KD who were selected by frequency matched based on sex, age, and the index year. The Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence intervals for the comparison of the 2 cohorts. The log-rank test was used to test the incidence of myopia in the 2 cohorts. A total of 532 patients were included in the KD cohort and 2128 in the non-KD cohort. The risk of myopia (hazard ratio, 1.31; 95% confidence interval, 1.08–1.58; P<0.01) was higher among patients with KD than among those in the non-KD cohort. The Cox proportional hazards regression model showed that irrespective of age, gender, and urbanization, Kawasaki disease was an independent risk factor for myopia. Patients with Kawasaki disease exhibited a substantially higher risk for developing myopia. [ABSTRACT FROM AUTHOR]

Objective: The purpose of our study was to determine the association of type 1 diabetes mellitus (T1DM) and the risk of herpes zoster (HZ). Methods: In this cohort study, we selected 4736 patients with T1DM registered in the Catastrophic Illness Patient Database who received insulin therapy before 2003 and 18944 participants without DM who were selected by frequency matched based on sex and age. Cox proportional hazard regression analysis was used to measure the hazard ratios (HRs) of HZ in the T1DM group compared with that in the non-T1DM group. Results: Cox proportional hazard regression analysis showed that the adjusted HR of HZ was 2.38 times higher for patients in the T1DM group (95% CI = 1.77–3.19) than for those in the non-T1DM group. According to diabetes severity, mild and serious T1DM patients were associated with a higher risk of HZ (adjusted HR = 2.26, 95% CI = 1.67–3.05; and adjusted HR = 5.08, 95% CI = 2.66–9.71, respectively) than subjects without T1DM. Conclusion: Patients with T1DM are at a higher risk of HZ than those without T1DM. [ABSTRACT FROM AUTHOR]

Objectives: Few studies have evaluated the association between Sjogren's syndrome (SS) and respiratory failure (RF). Thus, we conducted a retrospective national cohort study to investigate whether Sjogren's syndrome (SS) increases the risk of respiratory failure (RF). Methods: The cohort consisted of 4954 newly diagnosed patients with SS but without a previous diagnosis of RF, and 19816 patients as the comparison cohort from the catastrophic illnesses registry, obtained from the 2000–2005 period. All of the study participants were followed from the index date to December 31, 2011. We analyzed the association between the risk of RF and SS by using a Cox proportional hazards regression model, controlling for sex, age, and comorbidities. Results: The overall incidence rate of RF showed a 3.21-fold increase in the SS cohort compared with the comparison cohort. The adjusted HR of RF was 3.04 for the SS cohort compared with the comparison cohort, after we adjusted for sex, age, and comorbidities. The HRs of RF for patients with primary SS and secondary SS compared with the comparison cohort were 2.99 and 3.93, respectively (P for trend <.001). The HRs of RF increased as the severity of SS increased, from 2.34 for those with no inpatient care experience to 5.15 for those with inpatient care experience (P for trend <.001). Conclusion: This study indicates that clinical physicians should not only consider secondary SS but also primary SS as a critical factor that increases the risk of RF. [ABSTRACT FROM AUTHOR]

Background: The onset of chronic fatigue syndrome (CFS) has been shown to be associated with several immunological conditions such as infections or atopy. The aim of this study was to clarify the risk of chronic fatigue syndrome following the diagnosis of psoriasis, an immune-related dermatological disease, by analyzing the National Health Insurance Research Database of Taiwan. Method: 2616 patients aged 20 years or older with newly diagnosed psoriasis during 2004–2008 and 10,464 participants without psoriasis were identified. Both groups were followed up until the diagnoses of CFS were made at the end of 2011. Results: The relationship between psoriasis and the subsequent risk of CFS was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 2.27 and 3.58 per 1000 person-years among the non-psoriasis and psoriasis populations, respectively (adjusted hazard ratio [HR] = 1.48, with 95% confidence interval [CI] 1.07–2.06). In the stratified analysis, the psoriasis group were consistently associated with a higher risk of CFS in male sex (HR = 2.05, 95% CI 1.31–3.20) and age group of ≥ 60 years old (HR = 2.32, 95% CI 1.33–4.06). In addition, we discovered that the significantly increased risk of CFS among psoriasis patients is attenuated after they receive phototherapy and/or immunomodulatory drugs. Conclusions: The data from this population-based retrospective cohort study revealed that psoriasis is associated with an elevated risk of subsequent CFS, which is differentiated by sex and age. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The prevalence of hypothyroidism is high in haemodialysis (HD) patients and hypothyroidism increases all‐cause mortality in HD patients. Comorbidities are common in HD patients and are associated with both mortality and hypothyroidism. The aim of the study is to explore the effect of the interactions of comorbidities and hypothyroidism on all‐cause mortality in HD patients. Method: Patients with hypothyroidism (ICD‐9‐CM 244.0, 244.1, and 244.9) and matched patients without hypothyroidism in the Registry for Catastrophic Illness Patient Database of Taiwan Health Insurance from 2000 to 2010 were analyzed. The association of hypothyroidism and risk of all‐cause mortality was analyzed using Cox proportional hazard regression. Result: Nine hundred and eight HD patients with hypothyroidism and 3632 sex‐, age‐, gender‐ matched HD patients without hypothyroidism were analyzed. Hypothyroidism was associated with increased all‐cause mortality with an adjusted hazard ratio of 1.22 [95% confidence interval (CI): 1.10–1.36, P < 0.001]. TRT may decrease mortality associated with hypothyroidism (P < 0.001). There was a significant interaction (P = 0.04) between diabetes and hypothyroidism. There was no significant interaction found in hypothyroidism and the following comorbidities: hyperlipidaemia, hypertension, chronic obstructive pulmonary disease, coronary artery disease, stroke, peripheral arterial disease, asthma, congestive heart failure and cancer. Conclusion: Hypothyroidism is associated with increased all‐cause mortality in chronic HD patients. The interaction of hypothyroidism and diabetes, but not other common comorbidities in HD patients, has an effect on mortality risks. [ABSTRACT FROM AUTHOR]

Background This study is a nationwide population-based retrospective cohort study to investigate the risk for developing dementia in thalassemia population. Methods In a longitudinal cohort of 1 million insured people, we identified 871 thalassemia patients who were newly diagnosed between 2000 and 2004 and selected a comparison cohort of 3484 subjects without thalassemia. We analyzed the risks for thalassemia and dementia using Cox proportional hazard regression models to assess the dementia risk in thalassemia patients after adjusting for age, gender, insured amount, urbanization and comorbidities. Results The overall risks for developing dementia were 1.88-fold (95% CI = 1.10–3.21) in patients with thalassemia compared with the comparison cohort after adjusting for age, sex, insured amount, urbanization and comorbidities. The combined effects measured for patients afflicted with thalassemia and the comorbidities of diabetes, hypertension, CAD, head injury, depression, CKD, or substance-related disorder exhibited a significant association with hyperlipidemia risk compared with that measured for patients without thalassemia and without any counterpart comorbidities. In subgroup analysis, the HRs of dementia increased, from 1.69 (95% CI = 0.93–3.07) for those who had not undergone transfusion to 2.72 (95% CI = 1.09–6.78) for those experienced transfusion compared with the no thalassemia cohort (p for trend < 0.01). Conclusion Our long-term cohort study result showed that thalassemia should be considered a crucial risk factor for developing dementia. [ABSTRACT FROM AUTHOR]