The impact of timing and modalities of dental prophylaxis on the risk of 5-fluorouracil-related oral mucositis in patients with head and neck cancer: a nationwide population-based cohort study.

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.

Is Neonatal Hyperbilirubinemia Exposure Associated with a Risk of Autism Spectrum Disorder? A Nationwide Cohort Study.

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.

Association between asthma and risk of benign prostatic hyperplasia: a retrospective population-based study.

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.

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

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

Increased risk of chronic fatigue syndrome following psoriasis: a nationwide population-based cohort study.

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.

Increased risk of chronic fatigue syndrome in patients with inflammatory bowel disease: a population-based retrospective cohort study.

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.

Chronic retinoic acid treatment induces differentiation and changes in the metabolite levels of brown (pre)adipocytes.

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.

Zinc(II)-Histidine Induced Collagen Peptide Assemblies: Morphology Modulation and Hydrolytic Catalysis Evaluation.

Collagen-related materials have many potential biomedical applications because of their high biocompatibility and biodegradability. Designed collagen-mimetic peptides (CMPs) could self-assemble into supramolecular structures via a variety of interactions. In particular, metal-ligand interactions can induce microscale sizes of collagen assemblies. Our previous study also successfully applied metal-histidine coordination method to promote the self-assembly of CMPs into micrometers of constructs. In an effort to broaden the metal-induced strategies on assembling designed CMPs and explore the new insights into their assembly process, herein we designed and synthesized a series of short CMPs with one or more histidine residues incorporated into the peptides and used Zn(II) to induce the formation of collagen assembled microstructures. By altering the location and the number of histidine residues, we found that the assembly rate was significantly affected as well as the morphology of the assembled architectures. The CMPs containing terminal histidine residues were found to assemble into less ordered granulated and spherical microstructures while that with only one single histidine in its middle site could form pinwheel or floret-like constructs, showing that we could modulate the morphology of collagen assemblies by changing the location and number of Zn(II)-His coordination sites. Additionally, these CMPs also exhibited catalytic activities on ester hydrolysis in the presence of Zn(II) ions, which suggested that Zn(II)-CMP assemblies could be potentially applied to the development of artificial enzymes.

Risk of acute coronary syndrome after parathyroidectomy in patients with end-stage renal disease: A population-based cohort study in Taiwan.

AIM: Patients with end-stage renal disease (ESRD) who received parathyroidectomy (PTX) had persistently reduced levels of parathyroid hormone. This study investigated the risk of acute coronary syndrome (ACS) in patients with ESRD who underwent PTX using a nationwide health insurance claims database. METHODS: Of all ESRD patients, we selected 1047 individuals who had undergone PTX between 2000 and 2008 as the PTX group and 4188 patients who did not undergo PTX (non-PTX group) matched by propensity score. Multivariable Cox proportional hazards regression analysis was conducted for assessing the excess ACS risk for the PTX group compared to the non-PTX group. RESULTS: The mean follow-up periods were 4.63 and 4.04 years for the PTX and non-PTX groups, respectively. A significant reduction in the risk of ACS (adjusted hazard ratio = 0.74, 95% confidence interval = 0.57-0.96) was observed for the ESRD patients after PTX. CONCLUSIONS: Parathyroidectomy is associated with reduced risk of ACS in patients with ESRD.

Hypothyroidism is associated with all-cause mortality in a national cohort of chronic haemodialysis patients.

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.

Patients with Cerebral Stroke Have an Increased Risk of Gastroesophageal Reflux Disease: A Population-Based Cohort Study.

BACKGROUND: Medical complications following stroke often result in significant morbidity. This study was designed to investigate the prevalence and risk of gastroesophageal reflux disease (GERD) between patients with stroke and those without stroke in Taiwan. METHODS AND RESULTS: This retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. The study included 18,412 patients newly diagnosed as having stroke during 2000-2006 and 18,412 patients without stroke frequency-matched by sex, age, and index year. All patients were followed from the index date to December 31, 2011. The Cox proportional hazards regression model was used to estimate the GERD risk. The GERD risk was approximately 1.51-times higher in the stroke group than in the nonstroke group, after adjustment for age, sex, and the cumulative incidence of some comorbidities. GERD was positively associated with stroke; the male sex (adjusted hazard ratio [HR] = 1.31); an age of 65 years or older (adjusted HR = 1.11); hyperlipidemia (adjusted HR = 1.14); ischemic heart disease (adjusted HR = 1.27); renal disease (adjusted HR = 1.45); and use of aspirin (adjusted HR = 2.34), clopidogrel (adjusted HR = 1.41), and dipyridamole (adjusted HR = 1.30). CONCLUSIONS: This study indicates a significantly higher GERD risk in patients with stroke than in the nonstroke group. In clinical practice, neurologists should focus on the risk of GERD symptoms.

Adult asthma is associated with an increased risk of herpes zoster: A population-based cohort study.

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.

Association between allergic disease, sleep-disordered breathing, and childhood nocturnal enuresis: a population-based case-control study.

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.

Splenectomy increases the subsequent risk of systemic lupus erythematosus.

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.

Risk of asthma in patients with primary Sjögren's syndrome: a retrospective cohort study.

BACKGROUND: Sjögren's syndrome (SS) has been associated with bronchial hyperresponsiveness and asthma; however, no population-based cohort study has been performed. We evaluated the risk of asthma in patients with primary SS in a nationwide population. METHODS: We conducted a retrospective cohort study using data from the National Health Insurance Research Database in Taiwan. The primary SS group included 4725 adult patients diagnosed between 2000 and 2006. Each patient was frequency-matched with four people without SS by sex, age and year of diagnosis. The occurrence and hazard ratio (HR) of asthma was monitored by the end of 2011. RESULTS: The overall incidence density of asthma was 1.62-fold higher in the primary SS group than in the non-SS group (9.86 vs. 6.10 per 1000 person-years), with a multivariable Cox proportional hazards model measured adjusted HR of 1.38 [95% confidence interval (CI) = 1.21-1.58]. Stratified analyses by sex, age group, and presence of comorbidity revealed that asthma incidences were all higher in the primary SS group than in the non-SS group, and the relative HRs of asthma associated with primary SS were significant in all subgroups. CONCLUSION: Patients with primary SS are associated with an increased risk of developing asthma. We should pay more attention to this group of individuals and provide them with appropriate support.

Hyperglycemia and chronic liver diseases on risk of hepatocellular carcinoma in Chinese patients with type 2 diabetes--National cohort of Taiwan Diabetes Study.

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.

Association of inflammatory bowel disease with asthma risk: A nationwide cohort study.

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.

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

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

The Utilization of Chinese Herbal Products for Hyperthyroidism in National Health Insurance System (NHIRD) of Taiwan: A Population-Based Study.

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.

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

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