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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. [ABSTRACT FROM AUTHOR]

Dietary vitamin A status affects energy metabolism. The present study explored the effect of all‐trans retinoic acid (ATRA) on the expression levels of molecules and metabolites of brown adipocytes. Chronic ATRA treatment was initiated during the early stage (days 0‐8) or late stage (days 8‐12) of adipogenesis. Treatment with ATRA during the early and late stage of adipogenesis resulted in an increase in the expression level of Ucp1 and Cidea, genes highly expressed in brown adipocytes, on day 8 and day 12, respectively, whereas expression of Pgc‐1α, another gene expressed during brown adipogenesis, was unaffected by ATRA. Non‐targeted metabolomic analyses indicated that the pathways related to the glucose metabolism were affected by ATRA, irrespective of the differentiation stage. Cellular levels of glucose 6‐phosphate, fructose 6‐phosphate, citric acid, and succinic acid decreased after ATRA treatment on days 8 and 12. In contrast, glucose level was higher in ATRA‐treated cells on day 8, but it was lower on day 12. ATRA decreased the cellular level of aconitic acid, fumaric acid, and malic acid on day 12 but not on day 8. Furthermore, ATRA increased the expression level of Hxk2 and downregulated the expressions of G6pdh and Pfkl/Pfkp on day 8 but not on day 12. Together, the results indicate that the chronic treatment with ATRA stimulated the formation of activated brown adipocytes, eventually leading to alterations in the levels of cellular metabolites related to glucose metabolism. Significance of the study: Significance of the study treatment with all‐trans retinoic acid (ATRA) during the early and late stage of adipogenesis increased the expression of Ucp1 and Cidea, genes highly expressed in brown adipocytes, on day 8 and day 12. Cellular levels of glucose 6‐phosphate, fructose 6‐phosphate, citric acid, and succinic acid decreased after ATRA treatment on days 8 and 12. In contrast, glucose level was higher in ATRA‐treated cells on day 8, but it was lower on day 12. The present results indicate that ATRA stimulated the formation of activated brown adipocytes, eventually leading to alterations in the levels of cellular metabolites related to glucose metabolism. [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]

Brown/beige adipocytes dissipate energy as heat. We previously showed that brown/beige adipocytes are present in white adipose tissue (WAT) of fattening cattle. The present study examined the effect of vitamin A restriction on mRNA expression of brown/beige adipocyte-related genes. In Japan, fattening cattle are conventionally fed a vitamin A-restricted diet to improve beef marbling. Twelve Japanese Black steers aged 10 mo were fed control feed (n = 6) or vitamin A-restricted feed (n = 6) for 20 mo. Subcutaneous WAT (scWAT) and mesenteric WAT (mesWAT) were collected, and mRNA expression levels of molecules related to the function of brown/beige adipocytes (Ucp1, Cidea, Dio2, Cox7a, and Cox8b) as well as transcriptional regulators related to brown/beige adipogenesis (Zfp516, Nfia, Prdm16, and Pgc-1a) were evaluated. The vitamin A restriction significantly increased or tended to increase expression levels of Cidea and Pgc-1a in scWAT, and Cidea, Dio2, and Nfia in mesWAT. Previous studies revealed that the bone morphogenetic protein (Bmp) pathway was responsible for commitment of mesenchymal stem cells to brown/beige adipocyte-lineage cells. The vitamin A restriction increased expression of Bmp7 and some Bmp receptors in WAT. The interrelationship between gene expression levels indicated that expression levels of Nfia, Prdm16, and Pgc-1a were closely related to those of genes related to the function of brown/beige adipocytes in scWAT. Also, expression levels of Nfia, Prdm16, and Pgc- 1a were highly correlated with those of Alk3 in scWAT. In summary, the present results suggest that the vitamin A restriction increases the number or activity of brown/beige adipocytes through regulatory expression of transcriptional regulators to induce brown/beige adipogenesis, especially in scWAT of fattening cattle, which may be governed by the Bmp pathway. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the clinical effectiveness of influenza vaccination in patients with rheumatoid arthritis (RA). Methods: The present study was conducted by using the Taiwan National Health Insurance Research Database. In this retrospective nationwide study, we included 3748 RA patients who received influenza vaccinations in 2008, 2009 and 2010, and 3748 matched RA patients who did not receive influenza vaccinations. We followed the patients from 4 weeks after influenza vaccination to the end of the influenza season in each year. After adjustment for potential confounding factors, including disease‐modifying anti‐rheumatic drugs, we used the Cox proportional hazards regression model to analyze the clinical effectiveness of influenza vaccination. Results: The influenza vaccination rate in RA patients was 14.8% in 2008, 19.8% in 2009 and 9.50% in 2010. Receiving influenza vaccine was associated with reduced risk of hospitalization for septicemia, bacteremia or viremia (hazards ratio [HR] = 0.65, 95% CI = 0.45–0.94), and lower risk of mortality (HR = 0.62, 95% CI = 0.39–0.97). The effectiveness was particularly significant in elderly patients. Conclusions: RA patients receiving influenza vaccine have significantly lower morbidity and mortality, particularly in elderly patients. Further studies are needed to explore effective policies to increase the vaccination rate in elderly RA patients. [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]

Objectives: The risk of herpes zoster (HZ) between patients with psoriasis receiving and not receiving systemic therapy has received increasing attention. This study investigated the association of psoriasis with the risk of HZ. Methods: We conducted a population-based retrospective cohort study by using the Taiwan National Health Insurance Research Database. The psoriasis cohort consisted of 4077 patients with newly diagnosed psoriasis between 2000 and 2006. Each patient with psoriasis was frequency-matched with four people without psoriasis, by sex, age and index year. (nonpsoriasis cohort; 16308 subjects). Patients who received systemic therapy were classified as having severe psoriasis, whereas those who did not receive systemic therapy were classified as having mild psoriasis. The Cox proportional hazards regression analysis was conducted to estimate the association between psoriasis and HZ risk. Results: The overall incidence density rate of HZ in the psoriasis cohort than in the nonpsoriasis cohort (4.50 vs. 3.44 per 1,000 person-years), with a multivariable Cox proportional hazards model measured adjusted HR of 1.29 [95% confidence interval (CI) = 1.07–1.56]. In additional, compared with the nonpsoriasis cohort, the risk of HZ was higher in the severe psoriasis cohort than in the nonpsoriasis cohort (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.15–2.27). The comparison between psoriasis and nonpsoriasis cohorts revealed a greatest magnitude risk of HZ in women (adjusted HR, 1.36; 95% CI, 1.04–1.79), study participants in the age group of 20–39 years (adjusted HR, 1.77; 95% CI, 1.17–2.66), and study participants without any comorbidities (adjusted HR, 1.37; 95% CI, 1.02–1.84). Conclusions: Our results suggest that psoriasis is associated with an increased risk of HZ, which involves differences in sex and age. Although systemic therapy may have a major role in the risk of HZ, the intrinsic factors of psoriasis cannot be excluded. [ABSTRACT FROM AUTHOR]

Splenectomy may be necessary to treat systemic lupus erythematosus (SLE) patients with thrombocytopenia; however, whether performing a splenectomy on patients without SLE increases the subsequent risk of SLE remains unknown. Therefore, this study was conducted to determine the association between splenectomy and SLE. We conducted a cohort study by using data from the Taiwan National Health Institute Research Database to identify 10,298 patients with received a splenectomy between 2000 and 2006 and 41,192 participants without received a splenectomy who were selected by frequency matched based on sex, age, and the index year. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of developing SLE associated with splenectomy compared with patients who did not receive a splenectomy. During the study period, the overall incidence density rate of SLE was higher in the splenectomy cohort than in the non-splenectomy cohort (adjusted HR 10.55; 95 % CI 50.55-20.05). The incidence density rates of SLE in women and men who received a splenectomy were higher than those of patients who did not receive a splenectomy. Non-traumatic splenectomy increases the subsequent risk of SLE. The risk of SLE should be considered before performing a splenectomy, particularly in women and younger patients. [ABSTRACT FROM AUTHOR]

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. [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]

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]

Iron is essential for a variety of physiological processes. Hepatic iron overload acts as a trigger for the progression of hepatic steatosis to nonalcoholic steatohepatitis and hepatocellular carcinoma. In the present study, we aimed to study the effects of iron overload on cellular responses in hepatocytes. Rat primary hepatocytes (RPH), mouse primary hepatocytes (MPH), HepG2 human hepatoma cells and Hepa1-6 mouse hepatoma cells were treated with FeCl3. Treatment with FeCl3 effectively increased iron accumulation in primary hepatocytes. Expression levels of molecules involved in cellular signaling such as AMPK pathway, TGF-β family pathway, and MAP kinase pathway were decreased by FeCl3 treatment in RPH. Cell viability in response to FeCl3 treatment was decreased in RPH but not in HepG2 and Hepa1-6 cells. Treatment with FeCl3 also decreased expression level of LC-3B, a marker of autophagy in RPH but not in liver-derived cell lines. Ultrastructural observations revealed that cell death resembling ferroptosis and necrosis was induced upon FeCl3 treatment in RPH. The expression level of genes involved in iron transport varied among different liver-derived cells- iron is thought to be efficiently incorporated as free Fe2+ in primary hepatocytes, whereas transferrin-iron is the main route for iron uptake in HepG2 cells. The present study reveals specific cellular responses in different liver-derived cells as a consequence of iron overload. [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: 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: Similarities in the symptoms of chronic fatigue syndrome (CFS) and inflammatory bowel disease (IBD) have been observed as follows: severe disease activity in IBD correlates with severe fatigue, major psychiatric signs, the common use of medication, and bacterial translocation. One of several hypotheses for explaining the mechanisms underlying CFS suggests a similarity to the impaired intestinal mucosa of IBD. "This study investigated the risk of incident CFS among patients with IBD".Methods: We conducted a population-based retrospective cohort study by using Taiwan's National Health Insurance Research Database to evaluate the subsequent risk of CFS in patients with IBD, according to demographic characteristics and comorbidities. The exposure cohort comprised 2163 patients with new diagnoses of IBD. Each patient was randomly selected and frequency matching according to gender and age with four participants from the general population who had no history of CFS at the index date (control cohort). Cox proportional hazards regression analysis was conducted to estimate the relationship between IBD and the subsequent risk of CFS.Results: The exposure cohort had a significantly higher overall risk of subsequent CFS than that of the control group [adjusted hazard ratio (Christophi in Inflamm Bowel Dis 18(12):2342-2356, 2012) = 2.25, 95%, confidence interval (Aaron and Buchwald in Ann Intern Med 134(9 Pt 2):868-881, 2001; Farraye et al. in Am J Gastroenterol 112:241, 2017) 1.70-2.99]. Further analysis indicated a significantly higher risk of CFS in patients who were male (HR = 3.23, 95% CI 2.12-4.91), were older than 35 years, and had IBD but without comorbidity status, e.g. Cancers, diabetes, obesity, depression, anxiety, sleep disorder, renal disease (HR = 2.50, 95% CI 1.63-3.84) after adjustment.Conclusion: The findings from this population-based retrospective cohort study suggest that IBD, especially Crohn's disease, is associated with an increased risk of subsequent CFS. [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]

Objective: This population-based cohort study investigated the risk of developing peripheral arterial occlusive disease (PAOD) in patients with Bell’s palsy. Methods: We used longitudinal claims data of health insurance of Taiwan to identify 5,152 patients with Bell’s palsy newly diagnosed in 2000–2010 and a control cohort of 20,608 patients without Bell’s palsy matched by propensity score. Incidence and hazard ratio (HR) of PAOD were assessed by the end of 2013. Results: The incidence of PAOD was approximately 1.5 times greater in the Bell’s palsy group than in the non-Bell’s palsy controls (7.75 vs. 4.99 per 1000 person-years). The Cox proportional hazards regression analysis measured adjusted HR was 1.54 (95% confidence interval (CI) = 1.35–1.76) for the Bell’s palsy group compared to the non-Bell’s palsy group, after adjusting for sex, age, occupation, income and comorbidities. Men were at higher risk of PAOD than women in the Bell’s palsy group, but not in the controls. The incidence of PAOD increased with age in both groups, but the Bell’s palsy group to control group HR of PAOD decreased as age increased. The systemic steroid treatment reduced 13% of PAOD hazard for Bell’s palsy patients, compared to those without the treatment, but not significant. Conclusions: Bell’s palsy appears to be associated with an increased risk of developing PAOD. Further pathophysiologic, histopathology and immunologic research is required to explore the underlying biologic mechanism. [ABSTRACT FROM AUTHOR]

Purpose: To examine the long-term risk of essential tremor (ET) in migraine. Methods: Using population-based administrative data from a subset of the National Health Insurance Research Database (NHIRD) of Taiwan, we identified 22,696 newly diagnosed migraineurs (mean age 44.5 years) and a matched migraine-free cohort of 90,784 individuals in the period 2000–2008. Multivariable Cox proportional hazards regression analysis was conducted for assessing the ET risk for the migraine cohort compared to the migraine-free cohort. Results: After adjusting for covariates, the migraine cohort had a 1.83-fold increased risk (95% CI 1.50–2.23) of subsequent ET in comparison to the migraine-free cohort (8.97 vs. 4.81 per 10,000 person-years). In the subgroup analysis, patients with migraine were associated with higher risks of ET, regardless of gender, age or the existence of comorbidities. Conclusion: Our findings demonstrated an association between migraine and ET, suggesting a possible shared pathophysiology underpinning both disorders. [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 changes of the risk of peripheral arterial disease (PAD) in patients with end-stage renal disease after parathyroidectomy are scant. Methods: We used a nationwide health insurance claims database to select all dialysis-dependent patients with end-stage renal disease aged 18 years and older for the study population in 2000 to 2006. Of the patients with end-stage renal disease, we selected 947 patients who had undergone parathyroidectomy as the parathyroidectomy group and frequency matched 3746 patients with end-stage renal disease by sex, age, years since the disease diagnosis, and the year of index date as the non-parathyroidectomy group. We used a multivariate Cox proportional hazards regression analysis with the use of a robust sandwich covariance matrix estimate, accounting for the intra-cluster dependence of hospitals or clinics, to measure the risk of peripheral arterial disease for the parathyroidectomy group compared with the non-parathyroidectomy group after adjusting for sex, age, premium-based income, urbanization, and comorbidity. Results: The mean post-op follow-up periods were 5.08 and 4.52 years for the parathyroidectomy and non-parathyroidectomy groups, respectively; the incidence density rate of PAD in the PTX group was 12.26 per 1000 person-years, significantly lower than the data in the non-PTX group (24.09 per 1000 person-years, adjusted HR = 0.66, 95% CI = 0.46–0.94). Conclusion: Parathyroidectomy is associated with reduced risk of peripheral arterial disease in patients with end-stage renal disease complicated with severe secondary hyperparathyroidism. [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]

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]

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]

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]

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]

The ripple-based constant on-time (COT) control with ripple compensation has been widely adopted in buck converters in the recent years because of its simplicity, fast transient response, and high light-load efficiency. However, this control has the potential issues of instability and excessive load transient response with wide input/output voltage range conditions in the power management integrated circuit (PMIC) applications. In this article, an accurate adaptive COT control scheme is proposed to solve these problems. The control scheme achieves accurate output voltage, and nearly constant quality factor and well transient response over a wide-range operation with simple circuit. The small-signal model is also derived based on the describing function (DF) technique for design optimization. Finally, the simulations and experimental verifications were conducted to verify the proposed concepts. [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: 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]

Background. Cholangitis is the infectious disease involving the biliary tract, which may induce systemic inflammation. Bone loss is a well-known sequelae after systemic inflammatory disease, and one grave complication after osteoporosis is hip fracture. We want to know whether cholangitis can contribute to increased risk of hip fracture. Methods. All the patients diagnosed with cholangitis since January 1, 2001, to December 31, 2009, were assessed. All the subjects with cancer history, traumatic accident, and previous fracture were excluded. We selected the controls without cholangitis and matched the controls to cholangitis patients by age, sex, osteoporosis, and the use of steroid for more than 30 days by approximately 1:4 ratio. Results. There were 2735 subjects in the cholangitis cohort and 10915 in the noncholangitis cohort. There were 101 hip fractures in the cholangitis cohort with the incidence density of 7.58 per 1000 person-years. As for the noncholangitis cohort, 366 individuals suffered from hip fracture with the incidence density of 5.86 per 1000 person-years. The risk of hip fracture was higher in the cholangitis cohort with a 1.29-fold increased risk than the noncholangitis cohort (hazard ratio = 1.29, 95% confidence interval = 1.03-1.61). The association between cholangitis and the hip fracture was more prominent among subjects less than 65 years (hazard ratio = 2.65, 95% confidence interval =1.30-5.39) and the subjects without comorbidities (hazard ratio = 3.01, 95% confidence interval = 1.42-6.41). Conclusions. Cholangitis is associated with higher risk for hip fracture, especially among young subjects free from medical comorbidities. [ABSTRACT FROM AUTHOR]

Abstract: Background: Both migraine and asthma are common health problems in the general population. However, the association between these two disorders is yet to be fully explored. Objective: We examined whether adult patients with migraine are at a higher risk of asthma development. Methods: We used data retrieved from the National Health Insurance Research Database in Taiwan to conduct this nationwide population‐based cohort study. We identified 6647 patients aged 20‐60 years who were newly diagnosed with migraine between 2000 and 2005 for the migraine group and identified 26 588 patients without migraine for the nonmigraine group. Both groups were followed up until the end of 2011 to examine the incidence of asthma. Cox proportional hazards regression analysis was used to measure the hazard ratio (HR) of asthma in the migraine group compared with the nonmigraine group. Results: The HR of asthma development was 1.37 (95% confidence interval = 1.21‐1.56) for the migraine group compared with the nonmigraine group after adjustment for age, sex, occupational status, insurance premium, urbanization, comorbidities, and annual outpatient department visits. Further stratified analysis revealed that this risk was also significantly higher for both sexes and in the 40‐ to 60‐year age group. The main limitation of this study was that some relevant data were unavailable, such as pain medication prescriptions and family history of migraine and asthma. Conclusion: Adult patients with migraine are at a higher future risk of asthma development. [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]

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 objective of this study was to determine whether a new diagnosis of asthma is associated with a later diagnosis of herpes zoster (HZ) in a nationwide, retrospective, non-age limited, population-based cohort.Methods: We used data from the National Health Insurance Research Database in Taiwan. The asthma group consisted of all 40 069 patients in the database with newly diagnosed asthma and using asthma medications from 2000 through 2005. The nonasthma group comprised 40 069 age- and sex-matched patients without any asthma diagnosis. Cox proportional hazards regression analysis was applied to calculate the hazard ratio of HZ in the patients with asthma relative to those without asthma.Results: During a mean follow-up period of 8.77 years, the risk of HZ was 1.48-fold higher in the asthma group compared with that in the nonasthma group after adjustment for sex, age, comorbidities, inhaled and systemic corticosteroid use, and annual outpatient department visits to dermatologists. Additional stratified analyses revealed that the risk of HZ was significantly higher in patients of both sexes and those aged older than 21 years.Conclusions: Newly diagnosed adult patients with asthma have a significantly higher risk of developing HZ than do those without asthma. [ABSTRACT FROM PUBLISHER]

Preventing the arrival of invasive alien species ( IAS) is a major priority in managing biological invasions. However, information on introduction pathways is currently scattered across many data bases that often use different categorisations to describe similar pathways. This hampers the identification and prioritisation of pathways to meet the main targets of recent environmental policies., Therefore, we integrate pathway information from two major IAS data bases, IUCN's Global Invasive Species Database ( GISD) and the DAISIE European Invasive Alien Species Gateway, applying the new standard categorisation scheme recently adopted by the Convention on Biological Diversity ( CBD). We describe the process of mapping pathways from the individual data bases to the CBD scheme and provide, for the first time, detailed descriptions of the standard pathway categories. The combined data set includes pathway information for 8323 species across major taxonomic groups (plants, vertebrates, invertebrates, algae, fungi, other) and environments (terrestrial, freshwater, marine)., We analyse the data for major patterns in the introduction pathways, highlighting that the specific research question and context determines whether the combined or an individual data set is the better information source for such analyses. While the combined data set provides an improved basis for direction-setting in invasion management policies on the global level, individual data sets often better reflect regional idiosyncrasies. The combined data set should thus be considered in addition to, rather than replacing, existing individual data sets., Pathway patterns derived from the combined and individual data sets show that the intentional pathways 'Escape' and 'Release' are most important for plants and vertebrates, while for invertebrates, algae, fungi and micro-organisms unintentional transport pathways prevail. Differences in pathway proportions among marine, freshwater and terrestrial environments are much less pronounced. The results also show that IAS with highest impacts in Europe are on average associated with a greater number of pathways than other alien species and are more frequently introduced both intentionally and unintentionally., Synthesis and applications. Linking data bases on invasive alien species by harmonising and consolidating their pathway information is essential to turn dispersed data into useful knowledge. The standard pathway categorisation scheme recently adopted by the Convention on Biological Diversity may be crucial to facilitate this process. Our study demonstrates the value of integrating major invasion data bases to help managers and policymakers reach robust conclusions about patterns in introduction pathways and thus aid effective prevention and prioritisation in invasion management. [ABSTRACT FROM AUTHOR]

Traditional Chinese herbal products (CHPs) have been described in ancient medicine systems as treatments for various stroke-associated ailments. This study is aimed to investigate the prescription patterns and combinations of CHPs for ischemic stroke in Taiwan. Prescriptions of CHPs for ischemic stroke were obtained from the National Health Insurance Research Database (NHIRD) of Taiwan. Every prescription with a leading diagnosis of ischemic stroke made during 2000-2010 was analyzed. Descriptive statistics were applied to the pattern of co-prescriptions. Multiple logistic regression models were used to assess demographic and risk factors that are correlated with CHP use. The dataset of inpatient claims data contained information on 15,896 subjects who experienced ischemic stroke from 2000 to 2010. There was an average of 5.82 CHPs in a single prescription for subjects with ischemic stroke. Bu-yang-huan-wu-tang (BYHWT) (40.32%) was by far the most frequently prescribed formula CHP for ischemic stroke, and the most commonly used combination of two-formula-CHP was BYHWT with Shu-jin-huo-xue-tang (SJHXT) (4.40%). Dan Shen (16.50%) was the most commonly used single CHP for ischemic stroke, and the most commonly used combination of two single CHPs was Shi Chang Pua with Yuan Zhi (4.79%). We found that BYHWT and Dan Shen were the most frequently prescribed formula and single CHP for ischemic stroke, respectively. These results provide information about individualized therapy and may contribute to further pharmacologic experiments and clinical trials. [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]

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: 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]