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Background. Traditional Chinese Medicine (TCM) relieves associated symptoms of hyperthyroidism such as heat intolerance, palpitations, tremor, anxiety, weight loss, increased frequency of bowel movements, and shortness of breath. However, there are no studies regarding the core prescription patterns of herbal formula and single herbs for hyperthyroidism in Taiwan. Materials and Methods. This is a retrospective, observational study using the National Health Insurance Research Database (NHIRD) in Taiwan to analyze the prescription patterns of TCM. Demographic factors, such as sex, age, occupational status, and residential area, and the risk factors for hyperthyroidism were also studied. Results. The outpatient or/and inpatient services for hyperthyroidism receive 17,707 cases in a year. Overall, there were 13,394 newly diagnosed patients. TCM was used in 73% of the patients, and 77.3% of the patients were females. The acceptability of TCM was higher among female patients. Most patients were diagnosed with hyperthyroidism between the ages of 30 and 49 years. The most common comorbidity identified was diabetes mellitus. The most commonly prescribed Chinese herbal product (CHP) formula was Jia-Wei-Xia-Yao-San, while Xia-Ku-Cao was the most commonly prescribed single CHP. There was a high coprescription rate for Xuan-Shen, Bei-Mu, and Mu-Li. Conclusion. This study describes the core prescription pattern of TCM used in the treatment of patients with hyperthyroidism in Taiwan. The most frequently used CHPs could be potential candidates for future pharmacologic studies or clinical trials. [ABSTRACT FROM AUTHOR]

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]

Purpose: This study investigated the impact of dental prophylaxis on 5-fluorouracil (5-FU)–related oral mucositis (OM) according to the head and neck cancer (HNC) locations and treatment times. Methods: A total of 13,969 HNC participants, including 482 5-FU–related OM subjects and 13,487 comparisons were enrolled from the Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan between 2000 and 2008. All subjects were stratified into subgroups based on the times to perform chlorhexidine use, scaling, and fluoride application before 5-FU administration. The dental prophylaxis related to 5-FU–related OM was estimated by multiple logistic regression and represented with odds ratio (OR) and 95% confidence interval (CI). Results: Fluoride gel application and scaling significantly impacted on OM development (p < 0.001), and the joint effect of fluoride gel and scaling induced 5-FU–related OM (OR = 3.46, 95% CI = 2.39–5.01). The risk of OM was raised 2.25-fold as scaling within 3 weeks before 5-FU–related chemotherapy (95% CI = 1.81–2.81), and a 3.22-fold increased risk of OM while fluoride gel was applied during 5-FU–related treatment (95% CI = 1.46–7.13). Conclusion: Dental prophylaxis significantly affected 5-FU–related OM in the HNC population. A short interval between dental scaling or fluoride application and 5-FU administration may be associated with higher prevalence of OM. Scaling simultaneously combined with chlorohexidine promoted 5-FU–related OM in specific HNC patients excluding the oral cancer and nasopharyngeal cancer population. Proper timing of the prophylactic dental treatments prior to 5-FU therapy could reduce the risk to develop 5-FU–related OM. [ABSTRACT FROM AUTHOR]

Objective: The association between asthma and benign prostatic hyperplasia (BPH) has rarely been explored. We investigated whether male asthmatic patients had an increased risk of BPH by conducting this retrospective nationwide population-based study.Methods: We utilized data derived from the National Health Insurance Research Database (NHIRD) in Taiwan. A total of 9778 male patients aged >40 years who were newly diagnosed with asthma between 2000 and 2006 were included in the asthma group. Male enrollees without asthma were selected as the non-asthma group from the same database. Both the groups were followed up until the end of 2013. We performed Cox proportional hazard regression analysis to estimate the risk of BPH and transurethral resection of the prostate (TURP) in the male patients with asthma compared with that in those without asthma.Results: The risk of BPH and TURP in the asthma group was 1.40-fold (95% confidence interval [CI] = 1.30-1.42) and 1.30-fold (95% CI= 1.31-1.50) higher than that in the non-asthma group, respectively, after adjusting for comorbidities, relevant medications and number of annual outpatient visits.Conclusions: The male patients with asthma were found to have a higher risk of BPH than did those without asthma. [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: Type 1 diabetes (T1D) is one of the most common chronic diseases of childhood. Whether neonatal hyperbilirubinaemia increases the risk of T1D remains unclear. Aim: To estimate the association between neonatal hyperbilirubinaemia and phototherapy and the risk of T1D using a large nationwide population-based cohort. Methods: This retrospective study was conducted using data from the National Health Insurance Research Database in Taiwan from 2001 until 2005. Altogether, 23,784 neonates aged <30 days diagnosed with hyperbilirubinaemia and 47,568 neonates without hyperbilirubinaemia were enrolled and frequency-matched to the hyperbilirubinaemia group by gender, age, parental occupation and urbanisation. Cox regression analysis was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results: Of the 71,352 neonates included, those with hyperbilirubinaemia had a higher incidence of T1D (4.76 vs 2.68 per 10,000 person-years, p < 0.001) and an earlier mean age at onset of T1D [4.13 (2.80) vs 5.80 (2.67) years, p < 0.001] than those without hyperbilirubinaemia. After adjusting for confounding factors in multivariable analysis, the neonates with hyperbilirubinaemia had a 66% increased risk of developing T1D (HR 1.66, 95% CI 1.26–2.18). Girls had a 1.41-fold (HR 1.41, 95% CI 1.10–1.82) greater risk of T1D than boys. Additionally, neonates with a history of perinatal complications (HR 1.66, 95% CI 0.99–2.80) and neonatal infections (HR 2.13, 95% CI 1.45–3.15) had an increased subsequent risk of T1D. Conclusions: The results suggest that neonatal hyperbilirubinaemia is associated with a subsequently increased risk of childhood-onset T1D. Abbreviations: T1D, type 1 diabetes; CI, confidence interval; NHI, national health insurance; NHIA, National Health Insurance Administration; NHIRD, National Health Insurance Research Database; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; G6PD, glucose-6-phosphate dehydrogenase; LBW, low birthweight; HRs, hazard ratios. [ABSTRACT FROM AUTHOR]

Background: It has been unclear whether diabetes mellitus (DM) is positively associated with a risk of venous thromboembolism (VTE). In addition, whether the risk of VTE is altered in patients with type 1 diabetes (T1DM) has rarely been explored. Aim: We investigated whether patients with T1DM are at a relatively high risk of VTE development. Methods: We retrieved data from the National Health Insurance Research Database of Taiwan to conduct this retrospective cohort study. The T1DM group consisted of 4967 patients diagnosed as having T1DM before 2003. The non-T1DM group comprised 19 868 age- and sex-matched enrollees without T1DM. Cox proportional hazard regression analysis was used to investigate the hazard ratio of VTE in patients with T1DM relative to those without T1DM. Results: During a mean follow-up period of 8.61 years, the risk of VTE in the T1DM group was 5.33-fold higher than in the non-T1DM group after adjusting for dyslipidemia, hypertension, stroke, lower leg fracture or surgery, and obesity. Further stratified analysis revealed that the risk of VTE was significantly high in both sexes and in all age groups below the age of 60. Conclusion: T1DM appears to be an independent risk factor for VTE development. [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]

Background: Dystonia is a neurological syndrome typically resulting in abnormal postures. Objectives: We tested the role of physical injury as potential risk factor for development of dystonia using The National Health Insurance Research Database of Taiwan. Methods: We identified 65704 people who were coded in the database as having had peripheral traumatic injuries (ICD-9-CM 807–848 and 860–959) in the year 2000. Patients with traumatic brain or spine injuries were excluded from analysis. We matched them using purposive sampling with 65704 people in the database who had not suffered peripheral trauma. We looked then at the incidence of dystonia occurring at least 1 year from the date of the peripheral trauma until 2011. Psychiatric symptoms (depression and anxiety) and sleeps difficulties have been investigated as potential covariates. Results: We found 189 patients with dystonia (0.28%) in the trauma group, and 52 patients with dystonia (0.08%) in the non-trauma group. Trauma was independently associated with dystonia (adjusted HR = 3.12, 95% CI = 2.30–4.24). The incidence density of dystonia in the trauma group was 2.27 per 10000 person-years, while it was 0.71 per 10000 person-years in the non-trauma group Beyond the peripheral trauma, other variables associated to the incidence of dystonia included female sex, aged 40 years and above, depression and sleep disorders. Conclusion: These data from a large population dataset support traumatic injury as a risk factor for the development of dystonia. [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: Little is known about the associations between allergic disease, sleep-disordered breathing (SDB), and childhood nocturnal enuresis (NE). We examined whether allergic disease and SDB were associated with childhood NE. Methods: Data were assessed from the 2007-2012 Taiwan National Health Insurance Research Database. We enrolled 4308 children aged 5-18 years having NE diagnosis and age- and sex-matched 4308 children as the control group. The odds ratios of NE were calculated to determine an association with preexisting allergic disease and SDB. Results: A total of 8616 children were included in the analysis. Prevalence of allergic diseases and SDB was significantly higher for the NE group than the control group (all p < 0.001). After adjusting odds ratios for potential confounding factors, except asthma, children with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and obstructive sleep apnea (OSA) had significantly higher odds of NE compared with children never diagnosed. With stratification for sex, girls with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, OSA, and snoring had significantly higher odds of NE, compared with girls never diagnosed. Only boys with allergic rhinitis and OSA were associated with increased odds of NE. With stratification for age, children aged 5-12 years with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and OSA had significantly higher odds of NE compared with those never diagnosed. Odds of NE increased with the number of comorbid allergic diseases. Conclusions: Allergic diseases and SDB are associated with increased odds of childhood NE. The odds of NE increased with the number of comorbid allergic diseases present. [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]

In Oriental countries, combinations of Chinese herbal products (CHPs) are often utilized as therapeutic agents for chronic obstructive pulmonary disease (COPD). The effects of CHPs on COPD have been previously reported. This study aimed to analyze the frequency of prescription and usage of CHPs in patients with COPD in Taiwan. In this nationwide population-based cross-sectional study, 19,142 patients from a random sample of one million individuals in the Longitudinal Health Insurance Database 2000 (LHID 2000) of the National Health Insurance Research Database (NHIRD) were enrolled from 2000 to 2011. The multiple logistic regression method was used to evaluate the adjusted odds ratios for the utilization of CHPs. For patients with COPD, there was an average of 6.31 CHPs in a single prescription. The most frequently prescribed CHP for COPD was Xiao-Qing-Long-Tang (XQLT) (2.6%), and the most commonly used combination of two formula CHPs was XQLT with Ma-Xing-Gan-Shi-Tang (MXGST) (1.28%). The most commonly used single CHP for COPD was Bulbus Fritillariae (3.65%), and the most commonly used combination of two single CHPs was Bulbus Fritillariae with Puerariae Lobatae (1.09%). These results provide information regarding personalized therapies and may promote further clinical experiments and pharmacologic research on the use of CHPs for the management of COPD. Furthermore, we found that TCM usage was more prevalent among men, younger, manual workers, residents of Northern Taiwan, and patients with chronic bronchitis and asthma. This information on the distribution of TCM usage around the country is valuable to public health policymakers and clinicians. [ABSTRACT FROM AUTHOR]

Leukemia is the most common malignancy among all childhood cancers and is associated with a low survival rate in adult patients. Since 1995, the National Health Insurance (NHI) program in Taiwan has been offering insurance coverage for Traditional Chinese Medicine (TCM), along with conventional Western medicine (WM). This study analyzes the status of TCM utilization in Taiwan, in both pediatric and adult patients with leukemia. A retrospective cohort study was conducted using population-based National Health Insurance Research Database of Registry of Catastrophic Illness, involving patient data from 2001 to 2010 and follow-up data through 2011. The effectiveness of TCM use was evaluated. Relevant sociodemographic data showed that both pediatric and adult patients who were TCM users one year prior to leukemia diagnosis were more likely to utilize TCM services for cancer therapy. A greater part of medical expenditure of TCM users was lower than that of TCM nonusers, except little discrepancy in drug fee of adult patients. The survival rate is also higher in TCM users. Altogether, these data show that TCM has the potential to serve as an adjuvant therapy when combined with conventional WM in the treatment of patients with leukemia. [ABSTRACT FROM AUTHOR]

Purpose: The association between primary headaches, including tension-type headache (TTH) as one of the most common primary headache disorders, and dementia remains controversial. In this nationwide, population-based, retrospective, cohort study, we explored the potential association between TTH and dementia and examined sex, age, and comorbidities as risk factors for dementia. Methods: Using the Taiwan National Health Insurance Research Database (NHIRD) claims data, the sample included 13908 subjects aged ≥20 years with newly-diagnosed TTH in 2000–2006. The non-TTH group included 55632 randomly selected sex- and age-matched TTH-free individuals. All subjects were followed until dementia diagnosis, death, or the end of 2011. Patients with dementia, including vascular and non-vascular (including Alzheimer’s) subtypes, were identified using International Classification of Diseases Ninth Revision, Clinical Modification codes. Multivariate Cox proportional hazards regression models were used to assess the risk of dementia and dementia-associated risk factors, such as migraine and other medical comorbidities. Results: During the average follow-up of 8.14 years, the incidence density rates of dementia were 5.30 and 3.68/1,000 person-years in the TTH and non-TTH groups, respectively. Compared with the non-TTH group, the risks of dementia were 1.25 (95% confidence interval [CI], 1.11–1.42) and 1.13 (95% CI, 1.01–1.27) times higher in the women and >65-year-old TTH group, respectively. TTH patients with comorbidities had a higher risk of dementia. TTH patients had a greater risk of non-vascular dementia (hazard ratio, 1.21; 95% CI, 1.09–1.34) than the non-TTH group. Conclusion: TTH patients have a future risk of dementia, indicating a potentially linked disease pathophysiology that warrants further study. The association between TTH and dementia is greater in women, older adults, and with comorbidities. Clinicians should be aware of potential dementia comorbidity in TTH patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the annual trends of traditional Chinese medicine (TCM) use for prevalent and incident asthmatic adults in Taiwan from 2000 to 2011. The annual prevalence and incidence of asthma in adults among subgroups of sociodemographic factors were also investigated. Methods: A population-based study was conducted using a random sample with one million beneficiaries of all residents aged ≥18 years enrolled in the National Health Insurance program. Adults diagnosed with asthma were identified from the National Health Insurance Research Database. The annual prevalence and incidence of asthma in the adult population were estimated by using International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes to identify relevant cases from 2000 to 2011. Results: The number of annual prevalent cases of diagnosed asthma increased from 56,885 in 2000 to 101,535 in 2011. The prevalence increased significantly on annual basis, whereas the incidence rate fluctuated over time. The prevalence of TCM use by adults with asthma decreased significantly (p<0.05), from 38.58% in 2000 to 29.26% in 2011. The number of annual incident cases of diagnosed asthma decreased from 3,896 in 2000 to 2,684 in 2011. TCM use rates in asthma incident adults decreased significantly (p<0.05), from 54.24% in 2000 to 38.19% in 2011. Conclusion: The prevalence of TCM utilization is high among adults with asthma in Taiwan. However, our study demonstrated a substantial decrease in the annual prevalence of TCM use by prevalent and incident asthmatic adults in Taiwan from 2000 to 2011. In addition, the prevalence of TCM use was higher among incident cases, compared with those with prevalent cases. [ABSTRACT FROM AUTHOR]

Objective: Combinations of Chinese herbal products (CHPs) are widely used for ischemic heart disease (IHD) in Taiwan. We analyzed the usage and frequency of CHPs prescribed for patients with IHD. Methods: A nationwide population-based cross-sectional study was conducted, 53531 patients from a random sample of one million in the National Health Insurance Research Database (NHIRD) from 2000 to 2010 were enrolled. Descriptive statistics, the multiple logistic regression method and Poisson regression analysis were employed to estimate the adjusted odds ratios (aORs) and adjusted risk ratios (aRRs) for utilization of CHPs. Results: The mean age of traditional Chinese medicine (TCM) nonusers was significantly higher than that of TCM users. Zhi-Gan-Cao-Tang (24.85%) was the most commonly prescribed formula CHPs, followed by Xue-Fu-Zhu-Yu-Tang (16.53%) and Sheng-Mai-San (16.00%). The most commonly prescribed single CHPs were Dan Shen (29.30%), Yu Jin (7.44%), and Ge Gen (6.03%). After multivariate adjustment, patients with IHD younger than 29 years had 2.62 times higher odds to use TCM than those 60 years or older. Residents living in Central Taiwan, having hyperlipidemia or cardiac dysrhythmias also have higher odds to use TCM. On the contrary, those who were males, who had diabetes mellitus (DM), hypertension, stroke, myocardial infarction (MI) were less likely to use TCM. Conclusions: Zhi-Gan-Cao-Tang and Dan Shen are the most commonly prescribed CHPs for IHD in Taiwan. Our results should be taken into account by physicians when devising individualized therapy for IHD. Further large-scale, randomized clinical trials are warranted in order to determine the effectiveness and safety of these herbal medicines. [ABSTRACT FROM AUTHOR]

Purpose This study evaluated the effect of epilepsy on the development of hyperlipidemia (HL) in Taiwan. Methods We conducted a nationwide population-based cohort study based on data obtained from the National Health Insurance Research Database of Taiwan. We identified 990 cases involving patients whose epilepsy was newly diagnosed between 2000 and 2005, and we also selected a comparison cohort comprising 3960 patients without epilepsy. Cox proportional hazards regression models were used to examine the association between epilepsy and HL. Results The mean follow-up period was 6.63 years for the epilepsy cohort and 7.49 years for the comparison cohort. The incidence rate of HL was 1.28-fold higher in the epilepsy cohort than it was in the comparison cohort (34.14 vs. 26.96 per 1000 person-years), with an adjusted hazard ratio of 1.17 (95% confidence interval, 1.01–1.36) after adjusting the model to account for the effects of sex and comorbidities. The most at-risk patients were those aged 50 to 59 years (hazard ratio, 1.35; 95% confidence interval, 1.04–1.79). For the epilepsy patients, the combined effect of ischemic heart disease, hypertension, and diabetes was associated with a significantly higher risk of developing HL compared with the patients with neither epilepsy nor any comorbidity. Conclusions Middle-aged epilepsy patients are at a significantly higher risk of developing HL. The results could assist in explaining the high risk of cerebral and cardiac vascular disease in epilepsy patients. [ABSTRACT FROM AUTHOR]

Objective: Combinations of Chinese herbal products (CHPs) are widely used for Parkinson's disease (PD) in Taiwan. Thereby, we investigated the use of CHPs in patients with PD. Methods: This study was a population-based cohort study that analyzed the data of patients with PD from the National Health Insurance Research Database. A total of 9,117 patients were selected from a random sample of one million individuals included in this database. We used multiple logistic regression models to estimate the adjusted odds ratios of the demographic factors and analyzed the formula and single CHPs commonly used for PD. Results: Traditional Chinese medicine users were more commonly female, younger, of white-collar status, and residents of Central Taiwan. Chaihu-Jia-Longgu-Muli-Tang was the most commonly used formula, followed by Ma-Zi-Ren-Wan and then Shao-Yao-Gan-Cao-Tang. The most commonly used single herb was Uncaria tomentosa (Willd. ex Schult.) DC., followed by Gastrodia elata Blume and then Radix et Rhizoma Rhei (Rheum palmatum L., Rheum tanguticum Maxim. ex Balf., and Rheum officinale Baill.). Chaihu-Jia-Longgu-Muli-Tang and U. tomentosa (Willd. ex Schult.) DC. have shown neuroprotective effects in previous studies, and they have been used for managing non-motor symptoms of PD. Conclusion: Chaihu-Jia-Longgu-Muli-Tang and U. tomentosa (Willd. ex Schult.) DC. are the most commonly used CHPs for PD in Taiwan. Our results revealed the preferences in medication prescriptions for PD. Further studies are warranted to determine the effectiveness of these CHPs for ameliorating the various symptoms of PD, their adverse effects, and the mechanisms underlying their associated neuroprotective effects. [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]

Background: Colonic diverticular disease is a chronic gastrointestinal disorder. Previous studies have suggested that chronic gastrointestinal tract is involved in the pathophysiology of Parkinson's disease.Object: This study investigated the potential link between colonic diverticular disease and risk of Parkinson's disease.Methods: Data in this nationwide population-based cohort study were obtained from the National Health Insurance Research Database. Patients with colonic diverticular disease were identified from among 23.22 million insured Taiwanese residents who had been diagnosed between 2000 and 2005 and were aged ≥20 years (n = 23367). The comparison cohort included patients without colonic diverticular disease, matched by sex, age, and all comorbidities with the colonic diverticular disease patients cohort (n = 23367). Using univariable and multivariable Cox proportional hazard regression models, we estimated the adjusted hazard ratio (aHR) for PD with a 95% confidence interval (CI) after adjusting for age, sex, and all of comorbidities.Results: The risk of Parkinson's disease was higher in the CDD cohort than in the comparison cohort (HR = 1.27, 95%CI = 1.10-1.47). Compared with patients aged ≥65 years without CDD, the CDD patients in the equal age group had a 1.25-fold increased risk of PD (95% CI = 1.07-1.46).Conclusion: Colonic diverticular disease may be associated with an increased risk of Parkinson's disease. Thus, the risk of this neurodegenerative disease should be considered in patients with colonic diverticular disease. [ABSTRACT FROM AUTHOR]

Background Inflammation-related microvasculr disease, albuminuria, and rapid deterioration of renal function can accelerate the development of end-stage renal disease (ESRD). The role of hip fracture (HFr), a disorder that involves inflammation, in the development of ESRD has not been fully investigated. This study explored whether HFr increases the risk of ESRD. Methods Taiwan National Health Insurance inpatient claims were used to identify 83,550 patients newly diagnosed with HFr from 2000 to 2006, and 83,550 age- and sex-matched patients without HFr were randomly selected for comparison. Hazards of ESRD combined with HFr, comorbidities, including hypertension, hyperlipidemia, peripheral arterial disease, osteoporosis and asthma, and general health status, with Charlson comorbidity index (CCI), were assessed using data to the end of 2011. Results ESRD risk was 1.42-fold higher (95% confidence interval [CI]:1.29–1.33) in the HFr cohort than in the control group, which was computed using the Cox proportional model. Age-specific analysis revealed that the adjusted hazard ratios (aHRs) of ESRD for HFr patients increased slightly as age increased, with an aHR of 1.56 (95% CI:1.35–1.81) for patients 65–74 years old, which gradually decreased to 0.88 (95% CI:0.66–1.18) for patients ≥ 85 years old. ESRD risk increased as HFr severity increased, with an aHR of 6.71 (95% CI:5.90–7.63) for patients with severe HFr. Conclusion This study is the first to report that HFr, in combination with underlying osteoporosis-related chronic illness, microvascular disease and chronic inflammation, is associated with an increased risk of ESRD, particularly among relatively younger people. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

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.

Whether periodontitis is a risk factor for developing bipolar disorders (BD) has not been investigated. We aimed to determine whether periodontitis is associated with the subsequent development of BD and examine the risk factors for BD among patients with periodontitis.Using ambulatory and inpatient claims data from the National Health Insurance Research Database (NHIRD), we identified 12,337 patients who were aged at least 20 years and newly diagnosed with periodontitis between 2000 and 2004. The date of the first claim with a periodontitis diagnosis was set as the index date. For each patient with periodontitis, 4 subjects without a history of periodontitis were randomly selected from the NHIRD and frequency-matched with the patients with periodontitis according to sex, age (in 5-year bands), and index year.The periodontitis group had a mean age of 44.0 ± 13.7 years and slight predominance of men (51.3%). Compared with the subjects without periodontitis, the patients with periodontitis had higher prevalence of diabetes mellitus, hyperlipidemia, hypertension, ischemic heart disease, stroke, head injury, major depressive disorder, chronic obstructive pulmonary disease (COPD), and asthma (P < .001). The incidence rate of BD was higher in the periodontitis group than in the non-periodontitis group (2.74 vs 1.46 per 1000 person-year), with an adjusted hazard ratio of 1.82 (95% confidence interval = 1.59-2.08) after adjustment for sex, age, and comorbidities.The patients with periodontitis exhibited a significantly higher risk of developing BD. Keep the better oral hygiene to reduce periodontitis might be a preventive strategy for BD.

Background: Prior literatures have shown inflammatory bowel disease (IBD) could increase fibromyalgia (FM) risk. However, studies about gender and age distributions of FM risk among patients with IBD are rare. With large study samples, this study aimed to evaluate the FM risk among IBD patients with different gender and different age., Objective: We aim to estimate the FM risk among male and younger IBD patients with a large patient sample., Study Design: A retrospective cohort study was arranged in this research., Setting: The data used in this research were selected from the Taiwan National Health Insurance Research Database (NHIRD)., Methods: From the Taiwan NHIRD, we selected 4,510 patients with IBD and 18,040 randomly gender- and age-matched patients without a history of IBD from the beginning of 2000 to the end of 2005 to analyze the development of FM over a 12-year follow-up period (2000-2011). The Cox regression model was used to assess the effects of IBD on the risk of FM by adjusting for gender, age, and comorbidities, including hypertension, diabetes, hyperlipidemia, depression, anxiety, and sleep disorder., Results: After adjusting suitable covariates, the IBD patients had a greater FM risk (adjusted hazard ratio [aHR] 1.70, 95% confidence interval [CI] 1.59-1.83) than the controls. Male IBD patients had a higher FM risk than female IBD patients did (aHR 2.00, 95% CI 1.79-2.23 and aHR 1.52, 95% CI 1.38-1.67, respectively). The greatest age-specific FM risk occurred in the youngest IBD subgroup (= 39 years old) (aHR 1.92, 95% CI 1.68-2.19)., Limitations: The information about personal behaviors was unobtainable in the Taiwan NHIRD. Other risk factors for cardiovascular disease that might augment FM cannot be excluded entirely in this study., Conclusion: IBD is disclosed to be correlated with an enhanced risk to develop FM, particularly in male and younger IBD patients. For preventing FM, it is necessary to pay more attention to the management of the IBD patients. Future researches are needed to further confirm the findings in this study., Key Words: Inflammation, inflammatory bowel disease, fibromyalgia, Taiwan National Health Insurance Research Database.

Asthma has been described as an "acephalic migraine" and "pulmonary migraine." However, no study has investigated the temporal frequency of migraine development in patients with asthma, and the results of previous studies may be difficult to generalize.We investigated the effect of asthma on the subsequent development of migraine by using a population-based data set in Taiwan.We retrieved our study sample from the National Health Insurance Research Database. Specifically, 25,560 patients aged 12 years and older with newly diagnosed asthma were identified as the asthma group, and 102,238 sex and age-matched patients without asthma were identified as the nonasthma group. Cox proportional-hazards regression models were employed to measure the risk of migraine for the asthmatic group compared with that for the nonasthmatic group.The risk of migraine in the asthmatic group was 1.45-fold higher (95% confidence interval 1.33-1.59) than that in the nonasthmatic group after adjustment for sex, age, the Charlson comorbidity index, common medications prescribed for patients with asthma, and annual outpatient department visits. An additional stratified analysis revealed that the risk of migraine remained significantly higher in both sexes and all age groups older than 20 years.Asthma could be an independent predisposing risk factor for migraine development in adults.

No large-scale population-based cohort study has ever investigated the risk of developing chronic obstructive pulmonary disease (COPD) in patients with Sjögren syndrome (SS). This study evaluated the risk of COPD in women with primary SS (pSS) in a nationwide population.We used the data of the National Health Insurance Research Database of Taiwan to establish a pSS group consisting of 3013 female adults diagnosed between 2000 and 2005, and a non-SS group consisting of 12,052 women without SS matched by a propensity score. Incident COPD cases were identified to the end of 2011. The pSS group to non-SS group adjusted hazard ratios (aHRs) of COPD were estimated using multivariable Cox proportional hazards regression analysis.After a mean follow-up period of 7.99 years, the incidence of COPD was 1.4-fold greater in the pSS group than in the non-SS group (3.87 vs 2.77 per 1000 person-years) with an aHR of 1.39 (95% confidence interval [CI] = 1.10-1.75, P = 0.007). The COPD incidence was 7-fold greater for women aged 50 years and above than women aged 20 to 49, with the aHR of 4.24 (95% CI = 3.06-5.88, P < 0.001). Comorbidity increased the COPD risk further for women with pSS. Women with both pSS and comorbidity had an aHR of 3.11 (95% CI = 2.23-4.33, P < 0.001) for COPD, compared to those free of both pSS and comorbidity.Women with pSS are at a greater risk of developing COPD than those without SS. Patients with SS require close monitoring to prevent COPD development, particularly for those with comorbidity., Competing Interests: The authors have no conflicts of interest to disclose.

Previous studies suggest that an association between restless legs syndrome (RLS) and migraine exists. However, population-based data are unavailable in Asian cohorts. Our study thus aims to evaluate the association between migraine and RLS in a nationwide, population-based cohort in Taiwan and to examine the effects of age, sex, migraine subtype, and comorbidities on RLS development.Data from the Taiwan National Health Insurance Research Database were used. Patients aged 20 years or older with newly diagnosed migraine from 2000 to 2008 were included; 23,641 patients with newly diagnosed migraine and 94,564 subjects without migraine were randomly selected and followed until RLS development, withdrawal from the National Health Insurance, or until the end of 2011. A multivariate Cox proportional hazards regression model was used to explore the risk of RLS in patients with migraine after adjustment for demographic characteristics and comorbidities.Both cohorts were followed for a mean of 7.38 years. After adjustment for covariates, the risk of RLS was 1.42-fold higher (95% confidence interval = 1.13-1.79) in the migraine cohort than in the nonmigraine cohort (7.19 versus 3.42 years per 10,000 person-years). The increased risk was more prominent in males in the migraine cohort (1.87-fold increased risk, 95% confidence interval 1.22-2.85). Neither comorbidity status nor migraine subtype influenced the RLS risk.This population-based study demonstrated that migraine is associated with an increased risk of RLS compared with those without migraine, particularly in male patients with migraine and regardless of the comorbidity status.

The spleen is a crucial organ in humans. However, little is known about the association of venous thromboembolism (VTE) with splenic injury and splenectomy in trauma patients. The aim of this study was to determine the subsequent risk of VTE following splenic injury and splenectomy. A nationwide retrospective cohort study was conducted by analysing data from the National Health Insurance Research Database in Taiwan. We included 6,162 splenic injury patients (3,033 splenectomised and 3,129 nonsplenectomised patients) and 24,648 comparison patients who were selected by frequency match based on sex, age, and the index year during 2000-2006. All patients were followed until the occurrence of VTE, 31 December, 2011, death, or withdrawal from the insurance program. The age of patients with splenic injury was 41.93 ± 16.44 years. The incidence rates of VTE were 11.81, 8.46, and 5.21 per 10,000 person-years in the splenic injury patients with splenectomy, splenic injury patients without splenectomy, and comparison patients, respectively. Compared with the comparison cohort, splenic injury patients with splenectomy exhibited a 2.21-fold risk of VTE (95% confidence interval [CI], 1.43-3.43), whereas those without splenectomy exhibited a 1.71-fold risk of VTE (95% CI, 1.05-2.80). The overall incidence rate of VTE was 1.97-fold higher in the splenic injury cohort than the comparison cohort (95% CI, 1.38-2.81). Although splenectomy increased the risk of VTE 1.35-fold compared with no splenectomy, the difference was not statistically significant (95% CI, 0.74-2.45). These results may alert physicians and patients to the complications of splenic injury and splenectomy.

Migraine and restless legs syndrome (RLS) appear to be associated, but the relationship between tension-type headache (TTH) and RLS is unknown. This nationwide, population-based, retrospective cohort study explored the potential association between TTH and RLS.We identified 15,504 patients with newly diagnosed TTH from 2000 to 2007 and 62,016 individuals without TTH who were selected by frequency matched based on sex, age, and the index year. The study participants were followed until diagnosed with RLS, withdrawal from the NHI program, or the end of 2011. Cox proportional hazard models were used to identify risk factors for RLS in TTH patients.After adjusting for sex, age, comorbidity, and medications, TTH was significantly associated with an increased risk of RLS (hazard ratio [HR] = 1.57, 95% confidence interval [CI] = 1.22-2.02). The risk was most prominent in patients aged 20 to 39 years in the TTH group, which exhibited a 2.60-fold higher risk (95% confidence interval = 1.53-4.42) of RLS compared with the non-TTH group. The TTH group had a higher risk of RLS than that of the non-TTH group regardless of sex.Tension-type headache appears to be associated with an increased risk of developing RLS. This similarity to migraines may indicate that headache and RLS have a coincident pathophysiological mechanism, a possibility requiring further study. Clinicians should be more attentive to RLS as a possible comorbidity in patients with TTH.

Objective: We evaluated the risk of asthma development in adult patients with inflammatory bowel disease (IBD) in a nationwide population., Methods: A retrospective cohort study was conducted by using data retrieved from the Taiwan National Health Insurance Research Database. Patients, ages 20 year or older, with newly diagnosed IBD between 2000 and 2005 were identified and randomly frequency-matched (based on sex, age, and index year) with four times the number of enrollees without IBD from the general population. Both cohorts were followed up until the end of 2011 to examine the incidence of asthma. Cox proportional hazard regression analysis was used to measure the hazard ratios (HR) of asthma in the IBD cohort compared with that in the non-IBD cohort., Results: The IBD and non-IBD cohorts comprised 5260 patients with IBD and 21,040 participants, respectively. After adjustment for covariates, the IBD cohort exhibited a 1.50-fold increased risk for asthma (HR 1.50, [95% confidence interval {CI}, 1.32-1.71]). Further analysis according to the two major forms of IBD revealed that the adjusted HR of asthma was 1.46 (95% CI, 1.03-2.07) and 1.50 (95% CI, 1.31-1.72) in patients with ulcerative colitis and Crohn's disease, respectively, compared with the non-IBD cohort., Conclusion: After adjustment for comorbidities, patients with IBD were associated with a higher subsequent risk of asthma.

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., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Splenectomy has been suggested to have an impact on immunological function, and subsequent development of cancer has been recognized as a possible adverse effect of splenectomy. This study evaluated the possible association between splenectomy and malignancy in Taiwan., Methods: A cohort study consisted of including 2,603 patients with nontraumatic and 2,295 patients with traumatic splenectomy, and then randomly frequency matched with 4 participants without splenectomy. The Cox proportional hazard regression analysis was conducted to estimate the influence of splenectomy on cancer risk., Results: Both nontraumatic and traumatic splenectomy had a significantly higher risk for overall cancer development (adjusted hazard ratios are 2.64 and 1.29 for nontraumatic and traumatic reasons, respectively). After adjusting for age, sex, and comorbidities, patients with splenectomy were associated with significantly higher risks for developing certain gastrointestinal tract cancers, other head and neck cancers, and hematological malignancies, and the phenomenon is more prominent in nontraumatic splenectomy group., Conclusion: This nationwide population-based study found that people with splenectomy have higher risks of developing overall cancer, as well as certain site-specific cancers, especially for patients with nontraumatic reasons., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: An association between lichen simplex chronicus (LSC) and sexual dysfunction was explored. However, no data are available from investigations into the relationship between erectile dysfunction (ED) and LSC., Objectives: This retrospective population-based cohort study aimed to clarify the risk of ED associated with LSC., Methods: By using the Taiwan National Health Insurance Research dataset, we identified 5611 male patients who had been newly diagnosed with LSC from 2000 to 2004. The date of diagnosis was identified as the index date. LSC patients with incomplete demographic information or with a history of ED before the index date were excluded. In total, 22444 age-matched patients without LSC were randomly selected as the non-LSC group based on a 1:4 ratio. Subsequence occurrence of ED was measured until 2011. The association between LSC and the risk of developing ED was estimated using Cox proportional hazard regression model., Results: After adjusting for age and comorbidities, patients with LSC had a 1.74-fold greater risk of developing ED compared with those without LSC (95% confidence interval=1.44-2.10). LSC patients with comorbidities including diabetes, hyperlipidemia, hypertension, cardiovascular disease, peripheral arterial disease, chronic obstructive pulmonary disease, chronic kidney disease, depression, and anxiety were at a higher risk of ED compared with the non-LSC patients without comorbidities., Conclusions: LSC confers a greater risk in the development of ED. Physicians should be aware of the potential of ED occurrence in LSC patients.

This study examined whether glycated hemoglobin A1C (HbA1C) and chronic liver diseases are associated with hepatocellular carcinoma (HCC) risk in Type 2 diabetic patients. A retrospective cohort study consisting of 51,705 patients with Type 2 diabetes aged 30 and over enrolled in the National Diabetes Care Management Program before 2004 was used in Cox proportional hazards models. HbA1C was independently associated with HCC incidence, and multivariate-adjusted hazard ratio (HR) of HCC was 1.20 (95% confidence interval, CI: 1.02-1.41) for patients with a level of HbA1c ≥ 9% compared with patients with a level of HbA1c <7% after multivariate adjustment. We observed a significant linear trend in HCC incidence with increasing HbA1c (p for trend = 0.02, HR = 1.07, 95% CI = 1.01-1.12 for every 1% increment in HbA1c). We observed significant HRs of HCC for patients with a level of HbA1c ≥ 9% with alcoholic liver damage, liver cirrhosis, HBV, HCV and any one of chronic liver diseases compared with patients with a level of HbA1c <9% and no counterpart comorbidity in the entire sample (HR = 8.63, 95% CI = 1.41-52.68; HR = 5.02, 95% CI = 3.10-8.12; HR = 2.53, 95% CI = 1.10-5.85; HR = 1.79, 95% CI = 1.01-3.17; and HR = 3.59, 95% CI = 2.56-5.02, respectively). Our results suggest significant joint associations of HbA1c ≥ 9% and chronic liver diseases. Lifestyle or treatment interventions such as maintaining a satisfactory glycemic control and chronic liver diseases may reduce the burden of HCC., (© 2014 UICC.)

The aim of this study was to determine the risk of myasthenia gravis (MG) in patients with allergic or autoimmune thyroid disease in a large cohort representing 99% of the population in Taiwan. Data from the Taiwan National Health Insurance Database were used to conduct retrospective analyses. The study comprised 1689 adult patients with MG who were 4-fold frequency matched to those without MG by sex, age, and assigned the same index year. Multivariate logistic regression models were used to calculate the odds ratios and 95% confidence intervals for the association between allergic or autoimmune thyroid disease and MG. An increased subsequent risk of MG was observed in the patients with allergic conjunctivitis (AC), allergic rhinitis, Hashimoto thyroiditis, and Graves disease. The adjusted odds ratios (aORs) were 1.93 (1.71-2.18), 1.26 (1.09-1.45), 2.87 (1.18-6.97), and 3.97 (2.71-5.83), respectively. The aORs increased from 1.63 (1.43-1.85) in a patient with only 1 allergic or autoimmune thyroid disease to 2.09 (1.75-2.49) in a patient with 2 thyroid or allergic diseases to 2.82 (2.19-3.64) in a patient with ≥3 thyroid or allergic diseases. MG was associated with the cumulative effect of concurrent allergic and autoimmune thyroid disease with combined AC and Hashimoto thyroiditis representing the highest risk (aOR = 15.62 [2.88-87.71]). This population-based case-control study demonstrates the association between allergic or autoimmune thyroid disease and the risk of MG. The highest risk of subsequent MG was associated with combined AC and Hashimoto thyroiditis.

This nationwide population-based retrospective cohort study was used to evaluate the association between pneumoconiosis and peripheral arterial disease (PAD). We identified 3374 patients with pneumoconiosis from the catastrophic illness registry who were newly diagnosed from 2000 to 2005; 13,496 patients without pneumoconiosis from Longitudinal Health Insurance Database 2000 (LHID2000) were randomly frequency matched according to sex, age, and index year and used as a nonpneumoconiosis group. Multivariate Cox proportional hazards regression was used to calculate adjusted hazard ratios (HRs) of PAD in the pneumoconiosis group compared with the nonpneumoconiosis group. The mean follow-up years were 7.44 years in the pneumoconiosis group and 8.17 years in the nonpneumoconiosis group. The incidence density rate of PAD was 1.25 times greater in the pneumoconiosis group than in the nonpneumoconiosis group (8.37 vs 6.70 per 1000 person-years). After adjusting for sex, age, and comorbidities, the adjusted HRs of PAD for the pneumoconiosis group were 1.30 (95% CI = 1.08-1.57), compared with the nonpneumoconiosis group. The combined impacts of patients with pneumoconiosis and diabetes, hyperlipidemia, hypertension, ischemic heart disease, chronic obstructive pulmonary disease, and asthma showed a significant by joint association with PAD risk compared with patients with no pneumoconiosis and no counterpart comorbidity. Patients with pneumoconiosis have an independently higher risk of developing PAD. Physicians should include pneumoconiosis in evaluating PAD risk.

Studies on the association between pneumoconiosis and deep-vein thrombosis (DVT) and pulmonary thromboembolism (PE) are few. This study was based on data obtained from the Taiwan National Health Insurance Database from 2000 to 2006, with a follow-up period extending to the end of 2011. We identified 3719 pneumoconiosis patients and 14876 non-pneumoconiosis patients who were selected by frequency matched based on sex, age, and the index year. We analysed the risks of DVT and PE by using Cox proportional hazards regression models by including sex, age, and CCI score. The risk of developing PE was 1.90-fold in the patients with pneumoconiosis compared with the comparison cohort after adjustments for age, sex, and CCI score. By contrast, we did not observe significant effect of pneumoconiosis on DVT. However, the cumulative incidence curves for DVT were similar in the pneumoconiosis patients and non-pneumoconiosis patients. The multiplicative increased risks of PE were significant in patients with pneumoconiosis and CCI score of one and more. In conclusion, physicians should include pneumoconiosis in evaluating pulmonary embolism risk.

Study Design: A spinal cord injury (SCI) retrospective cohort study was derived from the National Health Insurance Research Database of Taiwan., Objective: We evaluated risk of acute myocardial infarction (AMI) in patients newly diagnosed with SCI., Summary of Background Data: According to information of the World Health Organization, cardiovascular diseases are the most frequent causes of death in patients with SCI compared with those in the general population., Methods: We obtained claims data from the National Health Insurance Research Database for this cohort study. The SCI group comprised 22,197 patients with a diagnosis of SCI. Case and control patients were based on risk-set sampling in a 1:4 ratio, and we excluded patients with a prior diagnosis of AMI. Comorbidities were categorized as the proportion of prior illnesses in the SCI and non-SCI groups. We used the Cox proportion model to explore adjusted hazard ratio (aHR) for developing AMI between case and control patients., Results: Patients with SCI were significantly more likely to exhibit pre-existing illnesses associated with AMI than patients without SCI. Patients with a diagnosis of SCI exhibited significantly higher aHRs for developing AMI than patients without SCI (aHR=1.17; P<0.05). Patients with SCI, compared with patients without SCI, were associated with a subsequent AMI risk (aHR=1.17; P<0.05). Several comorbidities, such as cardiovascular disease (aHR=1.29; P<0.05), chronic obstructive pulmonary disease (aHR=1.51; P<0.05), hypertension (aHR=1.34; P<0.01), and renal disease (aHR=1.76; P<0.05), were associated with an increased AMI risk. Furthermore, T-spine SCI was significantly associated with an AMI risk (aHR=1.38; P<0.05)., Conclusion: Patients with as diagnosis of SCI exhibited an increased risk of AMI compared with patients without SCI. These findings have broad implications for surveillance among patients with SCI, and future studies should evaluate whether risk factor modification can decrease AMI risk among patients with SCI., Level of Evidence: 3.

Objectives/hypothesis: Tonsillectomy is related to increased risk of certain types of cancer. This study evaluates the possible association between tonsillectomy and cancer in Taiwan., Methods: Data from the National Health Insurance system of Taiwan was used. A cohort study consisting of 997 patients with a new diagnosis of tonsillectomy from 2000 to 2005 and a comparison cohort of 3,988 subjects without tonsillectomy were used in the Poisson regression analysis to estimate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of cancers., Results: The incidence rate of all cancer types was higher in the tonsillectomy group than in the control group (4.28 vs. 2.97 per 1,000 person-years, respectively), with an IRR = 1.54 and 95% CI of 1.05 to 2.25, but the significant difference was limited to patients with more than 3 years follow-up. Site-specific analysis found no significant association between tonsillectomy and any individual cancer after adjusting for age, sex, hyperlipidemia, hypertension, and diabetes; however, tonsillectomy patients with more than 3 years follow-up had a marginally significantly higher risk for breast cancer development (adjusted IRR = 2.62; CI = 0.97-7.03)., Conclusion: Our study found that Taiwanese people with tonsillectomy have a significantly higher overall risk of developing cancer and a marginally higher risk of developing breast cancer when follow-up is longer than 3 years., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

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.

Objective: To determine the risk of osteoporosis in patients with myasthenia gravis (MG) in a large cohort representing 99% of the population of Taiwan., Methods: Data from the Taiwan National Health Insurance Research Database were used to conduct retrospective cohort analyses. The study cohort consisted of 2,073 patients with MG who were 3-fold frequency-matched by age and sex and assigned the same index year as a comparison cohort without MG. Cox proportional hazard regression analysis was conducted to estimate the risk of osteoporosis., Results: The MG cohort had a 1.96-fold increased risk of developing osteoporosis compared with the comparison cohort (hazard ratio [HR] = 1.96, 95% confidence interval [CI] = 1.57-2.44). Patients with MG older than 30 years developed an increased risk of osteoporosis, with the highest risk in the age group from 30 to 44 years, compared with the control cohort. Corticosteroid-naïve patients with MG had a 1.52-fold increased risk of developing osteoporosis (HR = 1.52, 95% CI = 1.11-2.08), and the corticosteroid-treated cohort had a 2.37-fold increased risk of developing osteoporosis (HR = 2.37, 95% CI = 1.82-3.07)., Conclusion: This population-based retrospective cohort study provides evidence that MG is associated with a high risk of osteoporosis regardless of corticosteroid use., (© 2014 American Academy of Neurology.)