Psychiatric disorders risk in patients with iron deficiency anemia and association with iron supplementation medications: a nationwide database analysis.

BACKGROUND: It has been shown that iron deficiency anemia (IDA) is associated with psychosocial consequences and psychiatric morbidity. However, the association between adults with IDA and psychiatric disorders has not been clarified. The purpose of this study was to investigate the psychiatric disorder morbidity of an IDA group in comparison with a non-IDA group and to examine the risk of psychiatric disorders in IDA patients treated with iron supplementation. METHODS: All study subjects were 20 years of age or over with newly diagnosed IDA enrolled in the Taiwan National Health Insurance Database from 2000 to 2012. We matched IDA and non-IDA subjects according to age and gender in a 1:2 ratio. Our primary outcome was diagnosis of psychiatric disorders and the patients were monitored until the end of 2013. A multivariate Cox proportional hazards regression model was used to explore the risk of psychiatric disorders in patients with IDA after adjustment for confounders, including demographic characteristics and comorbidities. RESULTS: The adjusted hazard ratios (aHRs) of psychiatric disorders was 1.52 (95% CI = 1.45-1.59) in the IDA group compared with the non-IDA group. Among the different types of psychiatric disorders, the IDA group was associated with significantly higher incidence and risks of anxiety disorders, depression, sleep disorders, and psychotic disorders (p <  0.05). Furthermore, iron supplementation in IDA subjects was associated with a significantly lower risk of psychiatric disorders compared to non-iron supplementation in IDA patients. CONCLUSIONS: Our study indicates that IDA subjects had an increased risk of psychiatric disorders, regardless of other confounders. In IDA patients, iron supplementation was associated with a decreased risk of psychiatric disorders. Moreover, IDA patients receiving iron supplementation also had a lower risk of sleep disorders.

Increased risk of fractures in patients with polycystic ovary syndrome: a nationwide population-based retrospective cohort study.

Polycystic ovary syndrome (PCOS) is a complex disorder; various features of this disorder may influence bone metabolism and skeletal mass. The contribution of PCOS to lower bone mineral density has been recognized. However, the impact of PCOS on the long-term risks for fractures remains inconclusive. The aim of this study was to determine the risk of overall fracture and fractures at different anatomic sites in patients with PCOS. Using a nationwide health insurance claims database, we included 11,106 subjects, aged 15-80 years, with newly diagnosed PCOS (ICD-9-CM: 254.4X) during 2000-2012. Patients with PCOS and respective age-matched (1:4) controls without PCOS were enrolled. The occurrence of fracture was monitored until the end of 2013. Cox regression and computed hazard ratios (HR) with 95% confidence intervals (95% CI) were used to determine the risk of PCOS among women with fractures. The PCOS and non-PCOS groups were comprised of 11,106 patients with PCOS and 44,424 participants without PCOS, respectively. Patients with PCOS had a higher incidence of any fractures compared with non-PCOS group (10.16 versus 8.07 per 1000 person-years) and a greater risk of any fractures [adjusted hazard ratio (aHR) = 1.23, 95% CI = 1.13-1.33], osteoporotic fractures (aHR = 1.33, 95% CI = 1.15-1.54), spine fractures (aHR = 1.36, 95% CI = 1.11-1.66) and forearm fractures (aHR = 1.39, 95% CI = 1.07-1.80), but the risk for femur or hip fracture, humerus, wrist and non-osteoporotic fractures were not increased. In conclusion, the PCOS group had a higher occurrence rate of fractures than the non-PCOS group. These results provide evidence for the adverse effects of PCOS on the risk of fractures.

Clinical outcome and prognostic factors associated with invasive pulmonary aspergillosis: An 11-year follow-up report from Taiwan.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) has high mortality rate but prognostic factors are not well established. The aim of our study was to evaluate the trend in in-hospital mortality over a period of 11 years and identify factors affecting the clinical outcomes of patients with IPA. METHOD: We conducted a nationwide inpatient population study using data from the Taiwan National Health Insurance Research Database. A total of 407 IPA patients from 2002 to 2012 were included in the study. Differences in demographics, comorbidities, and treatment were evaluated between in-hospital death group and survival group. Multivariate analysis was also performed to identify risk factors for mortality. RESULT: Male patients represented 63.14% of the patients (n = 257) and the mean age was 53.15 ± 20.93 years. Hematological cancer (n = 216, 53.07%) and diabetes mellitus (n = 75, 18.43%) were the most common underlying conditions. The overall case fatality rate was 30.22% with female slightly higher then male (32.67% versus 28.79%). The in-hospital case fatality rate increased since 2002 and peaked in 2006. It then declined over time with an in-hospital mortality of 25% in 2012. The in-hospital death group had a higher intubation rate (p<0.0001), a longer ICU stay (p = 0.0062), higher percentages of DM (p = 0.0412) and COPD (p = 0.0178), and a lower percentage of hematological cancer (p = 0.0079) as compared to survivor. The in-hospital death group was more likely to have steroid treatment (p<0.0001), develop acute renal failure (p<0.0001) and other infectious diseases (p = 0.0008) during hospitalization. Multivariate analysis identified female gender, older age (≥ 65 years old), intubation, bone marrow transplantation, acute renal failure, other infectious diseases and steroid use as predictive factors for mortality. CONCLUSION: The present study shows the trend in mortality among patients with IPA over an 11-year period. Female gender, older age, intubation, bone marrow transplantation, acute renal failure, other infectious diseases and steroid use were identified as risk factors for mortality.

Recent upper gastrointestinal panendoscopy increases the risk of pyogenic liver abscess.

AIM: To investigate the association between a recent gastrointestinal (GI) endoscopy and the subsequent risk of pyogenic liver abscess (PLA). METHODS: We designed a nested case control study. Using the Taiwan National Health Insurance Research Database, 2135 patients with a first diagnosis of PLA were identified from 1998 to 2011. Another 10675 patients without PLA matched by age and sex were selected as reference controls. We identified and compared the possible risk factors for PLA and GI endoscopies performed before the index date (when PLA was diagnosed) between the two cohorts. Multivariate analysis was conducted to examine the risk of PLA within the 90 d after the GI endoscopies. RESULTS: Patients with a history of diabetes [adjusted odds ratio (aOR) = 4.92, 95%CI: 1.78-13.61], end-stage renal disease (aOR = 3.98, 95%CI: 1.45-10.91), biliary tract infection (aOR = 2.68, 95%CI: 2.11-3.40), liver cirrhosis (aOR = 2.19, 95%CI: 1.39-3.46), GI malignancies (aOR = 5.68, 95%CI: 4.23-7.64), appendicitis (aOR = 3.16, 95%CI: 2.27-4.41), diverticulitis (aOR = 1.64, 95%CI: 1.01-2.64), and recent endoscopic retrograde cholangiopancreatography (aOR = 27.04, 95%CI: 11.65-62.72) were significantly associated with an increased risk of PLA. After adjusting for the above risk factors and the frequency of outpatient department visits and abdominal ultrasounds during 90 d before the index date, an upper GI panendoscopy (aOR = 2.75, 95%CI: 2.05-3.69) but not a lower GI endoscopy (aOR = 1.07, 95%CI: 0.62-1.86) was significantly associated with PLA. CONCLUSION: An upper GI panendoscopy performed before 90 d may increase the risk of PLA.

Predicting return visits to the emergency department for pediatric patients: Applying supervised learning techniques to the Taiwan National Health Insurance Research Database.

BACKGROUND AND OBJECTIVE: Return visits (RVs) to the emergency department (ED) consume medical resources and may represent a patient safety issue. The occurrence of unexpected RVs is considered a performance indicator for ED care quality. Because children are susceptible to medical errors and utilize considerable ED resources, knowing the factors that affect RVs in pediatric patients helps improve the quality of pediatric emergency care. METHODS: We collected data on visits made by patients aged ≤18years to EDs from the National Health Insurance Research Database. The outcome of interest was a RV within 3days of the initial visit. Potential factors were categorized into demographics, medical history, features of ED visits, physician characteristics, hospital characteristics, and treatment-seeking behavior. A multivariate logistic regression was used to identify independent predictors of RVs. We compared the performance of various data mining techniques, including Naïve Bayes, classification and regression tree (CART), random forest, and logistic regression, in predicting RVs. Finally, we developed a decision tree to stratify the risk of RVs. RESULTS: Of 125,940 visits, 6,282 (5.0%) were followed by a RV within 3 days. Predictors of RVs included younger age, higher acuity, intravenous fluid, more examination types, complete blood count, consultation, lower hospital level, hospitalization within one week before the initial visit, frequent ED visits in the past one year, and visits made in Spring or on Saturdays. Patients with allergic diseases and those underwent ultrasound examination were less likely to return. Decision tree models performed better in predicting RVs in terms of area under curve. The decision tree constructed using the CART technique showed that the number of ED visits in the past one year, diagnosis category, testing of complete blood count, and age were important discriminators of risk of RVs. CONCLUSIONS: We identified several factors which are associated with RVs to the ED in pediatric patients. The knowledge of these factors may help assess risk of RVs in the ED and guide physicians to reevaluate and provide interventions to children belonging to the high risk groups before ED discharge.

Chronic Kidney Disease is Associated With Upper Tract Urothelial Carcinoma: A Nationwide Population-Based Cohort Study in Taiwan.

Increased urinary tract malignancy has been reported in end-stage renal disease (ESRD). However, little is known about chronic kidney disease (CKD). This study is designed to explore the association between CKD and upper tract urothelial carcinoma (UTUC).Using Taiwan's Longitudinal Health Insurance Database, we studied CKD patients between January 2000 and December 2011. The non-CKD controls were selected at a ratio of 4:1 and frequency matched by gender, age group, and index date. We used the chi-square test and t test to analyze the sociodemographic information and comorbidities. Cox regression analysis was used to calculate the hazard ratio (HR) and 95% confidence interval (CI).The selected cases included 45,321 CKD cases and 181,284 controls. A significantly higher incidence of UTUC was noted in the CKD group (0.22% vs 0.07%, P < 0.001). In univariate analysis, CKD, female gender, age, hypertension, hematuria, repeated urinary tract infection, bladder cancer, and ESRD were all associated with UTUC. In multivariate analysis, only CKD, female gender, age, hematuria, bladder cancer, and ESRD were significantly associated. The HR for CKD was 1.63 (95% CI: 1.26-2.13). Females had a higher HR of 1.38 (95% CI: 1.11-1.71). After excluding those patients who progressed to dialysis or kidney transplantation, the risk for CKD was still high, with an HR of 1.72 (95% CI: 1.33-2.33).CKD is a significant factor associated with UTUC. We should pay attention to the possibility of UTUC for CKD patients before they progress to ESRD.

Infant Stool Color Card Screening Helps Reduce the Hospitalization Rate and Mortality of Biliary Atresia: A 14-Year Nationwide Cohort Study in Taiwan.

Biliary atresia (BA) is a significant liver disease in children. Since 2004, Taiwan has implemented a national screening program that uses an infant stool color card (SCC) for the early detection of BA. The purpose of this study was to examine the outcomes of BA cases before and after the launch of this screening program. The objectives of this study were to evaluate the rates of hospitalization, liver transplantation (LT), and mortality of BA cases before and after the program, and to examine the association between the hospitalization rate and survival outcomes.This was a population-based cohort study. BA cases born during 1997 to 2010 were identified from the Taiwan National Health Insurance Research Database. Sex, birth date, hospitalization date, LT, and death data were collected and analyzed. The hospitalization rate by 2 years of age (Hosp/2yr) was calculated to evaluate its association with the outcomes of LT or death.Among 513 total BA cases, 457 (89%) underwent the Kasai procedure. Of these, the Hosp/2yr was significantly reduced from 6.0 to 6.9/case in the earlier cohort (1997-2004) to 4.9 to 5.3/case in the later cohort (2005-2010). This hospitalization rate reduction was followed by a reduction in mortality from 26.2% to 15.9% after 2006. The Cox proportional hazards model showed a significant increase in the risk for both LT (hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 1.10-1.18) and death (HR = 1.05, 95% CI = 1.01-1.08) for each additional hospitalization. A multivariate logistic regression model found that cases with a Hosp/2yr >6 times had a significantly higher risk for both LT (adjusted odds ratio [aOR] = 4.35, 95% CI = 2.82-6.73) and death (aOR = 1.75, 95% CI = 1.17-2.62).The hospitalization and mortality rates of BA cases in Taiwan were significantly and coincidentally reduced after the launch of the SCC screening program. There was a significant association between the hospitalization rate and final outcomes of LT or death. The SCC screening program can help reduce the hospitalization rate and mortality of BA cases and bring great financial benefit.

Incidence and survival of retinoblastoma in Taiwan: a nationwide population-based study 1998-2011.

OBJECTIVE: To study the epidemiology of retinoblastoma in Taiwan from 1998 to 2011. DESIGN: This was a retrospective population-based cohort study using the Taiwan National Health Insurance Research Database. RESULTS: The present study included 154 patients (92 males, 62 females) with retinoblastoma and the documented overall retinoblastoma incidence was 1 in 17 373 live births without a notable trend over the study period. The incidence per million live births examined by gender was 65.8 for males and 48.5 for females. The age-specific sex ratio increased from 1.4 at age younger than 1 year to 3.0 above age 4 years. Enucleation was performed in 109 (70.8%) children with retinoblastoma, and it was more prevalent in males than in females (77.2% vs 61.3%, p=0.0335). Multivariate Cox regression analyses with adjustment for diagnostic age, sex, and birth year elucidated that enucleation was a significant factor associated with survival (OR 0.27, 95% CI 0.10 to 0.61). CONCLUSIONS: The incidence of retinoblastoma in Taiwan exhibited no marked trend over time. There were more cases of males than females and the male-to-female rate ratio increased with age. Survival outcome was significantly associated with the intervention of enucleation.

Relationship Between being Overweight and Iron Deficiency in Adolescents.

OBJECTIVE: Being overweight has been considered to be a risk factor of iron deficiency (ID). The objective of this study was to examine the relationship between being overweight and body iron status among Taiwanese adolescents. METHODS: A total of 2099 adolescents (1327 female) aged 12-19 years from four middle schools and one college in southern Taiwan participated in this study. Data on sex, age, body weight, height, hemoglobin concentration, plasma ferritin (PF), and serum iron (SI) levels were collected. According to the age- and sex-specific body mass index (BMI) percentiles, the participants were divided into four weight groups: underweight (<5(th) percentile), normal weight (5-84(th) percentile), overweight (85-94(th) percentile), and obese (≥95(th) percentile). A multivariate logistic regression model was used to estimate the odds ratio (OR) and the 95% confidence interval (CI) for each factor. RESULTS: The correlation coefficients of linear regression were positive for BMI-hemoglobin and BMI-PF, but negative for BMI-SI. Compared with the normal-weight group, the obese group had a lower risk of PF level <15 µg/L with an OR (95% CI) of 0.51 (0.30-0.87) but a higher risk of SI <60 µg/dL with an OR (95% CI) of 1.78 (1.34-2.37). The percentages of low PF declined as BMI increased, but the percentages of low SI rose, from underweight to obesity groups. CONCLUSION: The relationship between being overweight and depleted iron store depends on which indicator is used to define the iron deficiency. Being overweight or obese would not be a risk factor of ID in adolescents, if ID were defined by PF rather than SI level.

Cyproheptadine significantly improves the overall and progression-free survival of sorafenib-treated advanced HCC patients.

OBJECTIVE: Sorafenib is a recommended treatment for advanced hepatocellular carcinoma. The study is to evaluate the efficacy of sorafenib plus cyproheptadine compared with sorafenib alone in patients with advanced hepatocellular carcinoma. METHODS: A retrospective cohort study reviewed all consecutive advanced hepatocellular carcinoma cases with Child-Pugh Class A disease starting sorafenib treatment at our hospital from August 2012 to March 2013. They were followed up until 31 December 2013. A total of 52 patients were enrolled: 32 patients in the combination (sorafenib-cyproheptadine) group and 20 patients in the control (sorafenib alone) group. The response to treatment, overall survival and progression-free survival were compared. RESULTS: The median overall survival was 11.0 months (95% confidence interval: 6.8-15.1 months) in the combination group compared with 4.8 months (95% confidence interval: 3.1-6.6 months) in the control group (crude hazard ratio = 0.45, 95% confidence interval: 0.22-0.82). The median progression-free survival time was 7.5 months (95% confidence interval: 5.1-10.0 months) in the combination group compared with 1.7 months (95% confidence interval: 1.4-2.1 months) in the control group (crude hazard ratio = 0.43, 95% confidence interval: 0.22-0.86). Kaplan-Meier survival analysis revealed that both overall survival and progression-free survival in the combination group were significantly longer than that in the control group. The multivariate model found patients in the combination group were 76% less likely to die (adjusted hazard ratio = 0.24, 95% confidence interval: 0.10-0.58) and 82% less likely to have progression (adjusted hazard ratio = 0.18, 95% confidence interval: 0.08-0.44) during the 17 months of follow-up. CONCLUSION: Cyproheptadine may significantly improve survival outcomes of sorafenib-treated advanced hepatocellular carcinoma patients.

Cost-effectiveness of augmenting universal hepatitis B vaccination with immunoglobin treatment.

OBJECTIVE: To compare the cost-effectiveness of hepatitis B virus (HBV) control strategies combining universal vaccination with hepatitis B immunoglobulin (HBIG) treatment for neonates of carrier mothers. METHODS: Drawing on Taiwan's experience, we developed a decision-analytic model to estimate the clinical and economic outcomes for 4 strategies: (1) strategy V-universal vaccination; (2) strategy S-V plus screening for hepatitis B surface antigen (HBsAg) and HBIG treatment for HBsAg-positive mothers' neonates; (3) strategy E-V plus screening for hepatitis B e-antigen (HBeAg), HBIG for HBeAg-positive mothers' neonates; (4) strategy S&E-V plus screening for HBsAg then HBeAg, HBIG for all HBeAg-positive, and some HBeAg-negative/HBsAg-positive mothers' neonates. RESULTS: Strategy S averted the most infections, followed by S&E, E, and V. In most cases, the more effective strategies were also more costly. The willingness-to-pay (WTP) above which strategy S was cost-effective rose as carrier rate declined and was <$4000 per infection averted for carrier rates >5%. The WTP below which strategy V was optimal also increased as carrier rate declined, from $1400 at 30% carrier rate to $3100 at 5% carrier rate. Strategies involving E were optimal for an intermediate range of WTP that narrowed as carrier rate declined. CONCLUSIONS: HBIG treatment for neonates of HBsAg carrier mothers is likely to be a cost-effective addition to universal vaccination, particularly in settings with adequate health care infrastructure. Targeting HBIG to neonates of higher risk HBeAg-positive mothers may be preferred where WTP is moderate. However, in very resource-limited settings, universal vaccination alone is optimal.

Unexpected remission of hepatocellular carcinoma (HCC) with lung metastasis to the combination therapy of thalidomide and cyproheptadine: report of two cases and a preliminary HCC cell line study.

We reported two cases of hepatocellular carcinoma (HCC) with lung metastases who were treated with a combination of thalidomide and cyproheptadine. The use of cyproheptadine in these two cases was originally for skin itching. Follow-up CT images revealed a complete remission of HCC in both of them after treatment for 6 months and 6 weeks, respectively. A following experimental cell line study demonstrated that cyproheptadine effectively reduced the viability of two HCC cell lines.

Effects of maternal screening and universal immunization to prevent mother-to-infant transmission of HBV.

BACKGROUND & AIMS: Mother-to-infant transmission is the major cause of hepatitis B virus (HBV) infection among immunized children. There has been much debate about screening pregnant women and administering hepatitis B immunoglobulin (HBIG) to newborns. We analyzed the rate of HBV infection among children born to hepatitis B surface antigen (HBsAg)-positive mothers and whether HBIG administration reduces transmission. METHODS: We analyzed data from 2356 children born to HBsAg-positive mothers, identified through prenatal maternal screens. In addition to HBV vaccines, HBIG was given to all 583 children with hepatitis B e antigen (HBeAg)-positive mothers and to 723 of 1773 children with HBeAg-negative mothers. Serology tests for HBV were performed from 2007 to 2009, when children were 0.5-10 years old. RESULTS: A significantly greater percentage of children with HBeAg-positive mothers tested positive for antibodies against the hepatitis B core protein (16.76%) and HBsAg (9.26%) than children with HBeAg-negative mothers (1.58% and 0.29%, respectively; P < .0001 and <.001). Among the HBV-infected children, the rate of chronicity also was higher among children with HBeAg-positive mothers than children with HBeAg-negative mothers (54% vs 17%; P = .002). Similar rates of antibodies against the hepatitis B core protein (0.99% and 1.88%; P = .19) and HBsAg (0.14% and 0.29%; P = .65) were noted in children born to HBeAg-negative mothers who were or were not given HBIG. Infantile fulminant hepatitis developed in 1 of 1050 children who did not receive HBIG (.095%). CONCLUSIONS: Children born to HBeAg-positive mothers are at greatest risk for chronic HBV infection (9.26%), despite immunization. Administration of HBIG to infants born to HBeAg-negative mothers did not appear to reduce the rate of chronic HBV infection, but might prevent infantile fulminant hepatitis. Screening pregnant women for HBsAg and HBeAg might control mother-to-infant transmission of HBV.

Epidemiological features of infantile hypertrophic pyloric stenosis in Taiwanese children: a Nation-Wide Analysis of Cases during 1997-2007.

OBJECTIVE: To describe the epidemiological characteristics of infantile hypertrophic pyloric stenosis (IHPS) in ethnic Chinese children. MATERIALS AND METHODS: We reviewed the National Health Insurance claims database and analyzed data from children less than one year of age who had been diagnosed with IHPS (ICD-9-CM 750.5) and had undergone pyloromyotomy (ICD-9-CM 43.3). We analyzed the incidence, gender, age at diagnosis, length of hospital stay, seasonal variation and cost of IHPS from data collected between January 1997 and December 2007. RESULTS: A total of 1,077 infants met inclusion criteria, including 889 boys and 188 girls. The annual incidence of IHPS ranged from 0.30 to 0.47 per 1,000 live births with a mean incidence of 0.39 per 1,000 live births. Between 2002 and 2007, the incidence showed a declining trend (P = 0.025) with coincidentally increasing trends for both exclusive breastfeeding (P = 0.014) and breastfeeding plus bottle feeding (P = 0.004). The male-to-female rate ratio was dynamic and increased from 3.03 during the first two weeks of life to 8.94 during the 8(th) through 10th weeks of life. The overall male-to-female rate ratio was 4.30. The mean age at diagnosis was 43.1 ± 2.4 days. After analyzing the months of birth and hospital admission, no seasonal variation associated with IHPS was detected. The mean length of hospital stay was 8.28 ± 7.10 days. CONCLUSIONS: The incidence of IHPS in Taiwan, a country with a majority ethnic Chinese population, was lower than observed incidences in Caucasian populations living in Western countries. Breastfeeding campaigns and low maternal smoking rates may contribute to the lower incidence of IHPS in Taiwan. However, additional studies with longer follow-up periods are needed.

Inhibitory effects of albuterol and fenoterol on RANTES and IP-10 expression in bronchial epithelial cells.

Short-acting ß2-adrenoreceptor agonist (SABA) is the major asthma reliever as indicated in the GINA guidelines. Regulated on activation, normal T expressed and secreted (RANTES) is a chemokine that attracts eosinophils, mast cells, and basophils toward site of allergic inflammation. Interferon γ-inducible protein (IP)-10 is a Th1-related chemokine that is also important in asthmatic inflammation and also involved in our immune defense against pathogens. Bronchial epithelial cells are first-line barrier against invasive pathogen and also have immunomodulatory function. However, whether albuterol and fenoterol (two SABAs) have modulatory effects on RANTES and IP-10 expression in bronchial epithelial cells is unknown. The human bronchial epithelial cell lines, BEAS-2B cells, were pre-treated with different concentrations of albuterol, fenoterol or dibutyryl-cAMP (a cyclic AMP analog) before polyinosinic-polycytidylic acid (poly I:C) stimulation. In some condition, BEAS-2B cells were pre-treated with ICI-118551, a selective ß2-adrenoreceptor antagonist, 30 min before albuterol or fenoterol treatment. The levels of RANTES and IP-10 were measured by ELISA. Intracellular signaling was investigated using cAMP assay, mitogen-activated protein kinase (MAPK) inhibitor, nuclear factor (NF)-κB inhibitor, and western blot. Albuterol and fenoterol suppressed poly I:C-induced RANTES and IP-10 expression of BEAS-2B cells. ICI-118551 could partly reverse the suppressive effects of albuterol and fenoterol on RANTES and IP-10 expression. Albuterol and fenoterol increased intracellular cAMP levels. Dibutyryl-cAMP conferred the similar effects of albuterol and fenoterol. Western blot revealed that albuterol suppressed p-ERK, p-JNK and pp38, and also their associated kinase expression. Albuterol had no effect on pp65 expression. Albuterol and fenoterol could suppress poly I:C-induced RANTES and IP-10 expression in human bronchial epithelial cells via at least partly the ß2-adrenoreceptor-cAMP and the MAPK pathways, implicating that albuterol and fenoterol could exert anti-inflammatory effect and benefit asthmatic patients by suppressing RANTES and IP-10 expression. However, these suppressive effects of albuterol and fenoterol may inhibit the defense against viral infection.

Suppressive effects of procaterol on expression of IP-10/CXCL 10 and RANTES/CCL 5 by bronchial epithelial cells.

As indicated in the Global Initiative for Asthma guidelines, short-acting ß2-adrenoreceptor agonists (SABAs) are important relievers in asthma exacerbation. Interferon γ-inducible protein (IP)-10/CXCL 10 is a T-helper type 1 (Th1) cell-related chemokine which is important in the recruitment of Th1 cells involved in host immune defense against intracellular pathogens such as viral infection. Regulated on activation, normal T expressed and secreted (RANTES)/CCL 5 is a chemokine which plays a role in attractant of eosinophils, mast cells, and basophils toward the site of allergic inflammation. Bronchial epithelial cells are first-line barriers against pathogen invasion. However, whether SABAs have regulatory effects on the expression of IP-10 and RANTES in bronchial epithelial cells is unknown. BEAS-2B cells, the human bronchial epithelial cell lines, were pretreated with procaterol (one of the SABAs) or dibutyryl-cAMP (a cyclic AMP analog) at different doses for 1 h and then stimulated with poly I:C (10 µg/mL). Supernatants were collected 12 and 24 h after poly I:C stimulation to determine the concentrations of IP-10 and RANTES by ELISA. In some cases, the cells were pretreated with selective ß2-adrenoreceptor antagonist, ICI-118551, 30 min before procaterol treatment. To investigate the intracellular signaling, the cells were pretreated with mitogen-activated protein kinase (MAPK) inhibitors and a NF-κB inhibitor 30 min before procaterol treatment. Western blot was also used to explore the intracellular signaling. Procaterol significantly suppressed poly I:C-induced IP-10 and RANTES in BEAS-2B cells in a dose-dependent manner. ICI-118551, a selective ß2-adrenoreceptor antagonist, could significantly reverse the suppressive effects. Dibutyryl-cAMP could confer the similar effects of procaterol on poly I:C-induced IP-10 and RANTES expression. Data of Western blot revealed that poly I:C-induced p-ERK, p-JNK, and pp38 expression, but not pp65, were suppressed by procaterol. SABAs could suppress poly I:C-induced IP-10 and RANTES expression in bronchial epithelial cells, at least in part, via ß2-adrenoreceptor-cAMP and MAPK-ERK, JNK, and p38 pathways.

Epidemiology of childhood intussusception and determinants of recurrence and operation: analysis of national health insurance data between 1998 and 2007 in Taiwan.

BACKGROUND: To study the epidemiology of childhood intussusception and risk factors of recurrence and operation based on a nationwide data. METHODS: Children with hospitalization due to intussusception (ICD9: 560.0) between 1998 and 2007 were identified from a national health insurance database. The incidence was calculated by age, sex, calendar year and month of admission. Recurrence and operation rates, duration and costs of hospitalization were analyzed. RESULTS: A total of 8217 intussusception-related hospitalizations were identified in 7541 children. The incidence of intussusception peaked between 3 and 36 months of age. Male -to-female incidence rate ratio increased from 1.31 in the first year to 2.52 in the ninth year of life. The overall recurrence and operation rates were 7.9% and 24.9%, respectively. In children less than 1 year old, the recurrence rate was 10.1%, which decreased to 5.3% in children over 3 years old. Multiple logistic regression analysis showed that children receiving operation had a significantly lower risk of recurrence with an odds ratio (95% confidence interval) of 0.31 (0.24-0.41) after controlling for age and sex. There are significantly more cases occurring during the warmer months between May and October compared to the cooler months between November and April. CONCLUSIONS: There was a male predominance of intussusception with a dynamic male-to-female incidence rate ratio. Children under 1 year of age have the highest recurrence and operation rates. Seasonal variation of intussusception was suspected in Taiwan.

Impact of non-occupational exposure to polybrominated diphenyl ethers on menstruation characteristics of reproductive-age females.

Polybrominated diphenyl ethers (PBDEs) have documented effects on thyroid functions and rodent behavior in vivo. Epidemiological studies, however, have revealed only limited information about associations between PBDE exposure and menstruation characteristics. Our goal was to examine whether high breast milk PBDE levels in reproductive-age females lead to interference with menstruation characteristics. We analyzed 15 PBDE congeners in 46 breast milk samples. Fifteen PBDE congeners (BDE-15, 28, 47, 49, 99, 100, 153, 154, 183, 196, 197, 203, 207, 208, and 209) were analyzed using a gas chromatograph equipped with a high resolution mass spectrometer. The mean sum of PBDEs (SigmaPBDEs) in breast milk was 3.42 ng/g lipid. Women's age at menarche was not correlated with breast milk PBDE levels. Increased BDE-208 and 209 levels were significantly associated with the prolonged length of average and the longest menstrual cycle independent of age, pre-pregnant BMI, and parity. Higher concentrations of SigmaPBDEs and the higher brominated PBDEs from BDE-183 to 209, except 197, were significantly linked to women whose menstruation periods were still coming irregularly at the sampling time. Age-adjusted odds ratios (ORs) of BDE-153, 183, 207, 208, and SigmaPBDEs were significantly higher in women with length of average menstrual cycle >32 days, compared to the control. Women whose menstruation periods still came irregularly when they were 18 years old had higher age-adjusted ORs of BDE-207, 208, 209, and SigmaPBDEs than those whose periods came regularly at the same age. Although SigmaPBDEs and certain higher brominated PBDEs appear to have potential to prolong length of average menstrual cycle and delay the age when menstruation periods begin coming regularly, these findings are not conclusive because our sample size is small and more scientific evidence is needed.

Concentrations of polybrominated diphenyl ethers in breast milk correlated to maternal age, education level, and occupational exposure.

The aim of the present study is to determine whether levels of polybrominated diphenyl ethers in breast milk in the general population are associated with demographic parameters, socioeconomic status, lifestyle factors, and occupational exposure. Forty-six participants are randomly selected from healthy women recruited between April 2007 and April 2008 from local hospitals in southern Taiwan. Thirty PBDE isomers in breast milk are analyzed using a gas chromatograph with a high resolution mass spectrometer. The mean+/-standard deviation of Sigma PBDEs in breast milk is 3.59+/-1.07 ng/g lipid. Our current value of Sigma PBDEs in breast milk is 0.7-fold lower compared to the past value in our previous study between 2000 and 2001. Higher levels of Sigma PBDEs might be significantly associated with older maternal age and maternal age of the present study is between 22 and 42 years old. Levels of Sigma PBDEs and certain PBDEs in breast milk are not correlated with maternal pre-pregnant BMI (Body mass index), parity, and lipid contents of breast milk. The Sigma PBDEs level in breast milk is lower in more educated women after controlling for age and pre-pregnancy BMI in our subjects. The main factors associated with Sigma PBDEs in breast milk are age and education level among the binary variables of demographic, socioeconomic, and lifestyle characteristics in this report. The exploratory relationships are found between PBDEs in breast milk and age, education level, or occupational exposure due to small sampling size.