Increased short- and long-term risk of sleep disorders in people with traumatic brain injury.

This study aims to evaluate the relationship between traumatic brain injury (TBI) and sleep disorders (SDs). We first initiated a questionnaire-based clinical survey to assess sleep problems in the early stage after a TBI, followed by a population-based cohort study to evaluate the long-term risk of SDs in TBI patients. For short-term clinical survey, mild (m)TBI patients and healthy controls were recruited to evaluate the sleep quality and daytime sleepiness using the Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) within two weeks after a TBI. For long-term observation, a 5-year nationwide population-based cohort study that utilized a large administrative database was conducted. In the short-term survey, 236 mTBI patients and 223 controls were analyzed. Total scores of the PSQI and ESS were significantly higher in mTBI patients than in the controls. In the long-term cohort study, 6932 TBI cases and 34,660 matched controls were included. TBI cases had a 1.36-fold greater risk of SDs compared to the non-TBI controls during the 5-year follow-up period. Results showed that patients with TBI had a significantly higher risk of SDs than did controls both in the early stage and during a 5-year follow-up period.

Urolithiasis is associated with an increased risk of stroke: a population-based 5-year follow-up study.

BACKGROUND: Epidemiological studies have reported an association between urolithiasis and cardiovascular disease. However, studies examining the risks of ischaemic and haemorrhagic stroke in patients with urolithiasis are limited. AIMS AND METHODS: By using a nationwide population database, we conducted a matched cohort study to investigate the association between urolithiasis and longitudinal risks of ischaemic and haemorrhagic stroke. RESULTS: The urolithiasis and non-urolithiasis cohorts included 12 979 and 64 895 patients respectively. Of these, 728 (5.6%) and 2802 (4.3%) patients in the urolithiasis and non-urolithiasis cohorts, respectively, had a stroke during the 5-year follow-up period. The hazard ratio (HR) for stroke was 1.19 times higher (95% confidence interval [CI] = 1.10-1.29; P < 0.001) in the urolithiasis cohort than in the non-urolithiasis cohort after adjustment for potential confounders. The risk of both ischaemic (adjusted HR = 1.16; 95% CI = 1.05-1.29) and haemorrhagic stroke (adjusted HR = 1.30; 95% CI = 1.03-1.64) remained significant in the urolithiasis cohort. Furthermore, the risk of stroke was significant in both men (adjusted HR = 1.16; 95% CI = 1.05-1.28) and women (adjusted HR = 1.26; 95% CI = 1.10-1.45). Middle-aged (40-59 years; adjusted HR = 1.26; 95% CI = 1.10-1.45) and older (≥60 years; adjusted HR = 1.14; 95% CI = 1.03-1.27) patients had a particularly high risk of stroke. CONCLUSIONS: The present study detected an increased risk of both ischaemic and haemorrhagic stroke in patients with urolithiasis, particularly in those older than 40 years.

Front-line intraperitoneal versus intravenous chemotherapy in stage III-IV epithelial ovarian, tubal, and peritoneal cancer with minimal residual disease: a competing risk analysis.

BACKGROUND: In the analysis of survival data for cancer patients, the problem of competing risks is often ignored. Competing risks have been recognized as a special case of time-to-event analysis. The conventional techniques for time-to-event analysis applied in the presence of competing risks often give biased or uninterpretable results. METHODS: Using a prospectively collected administrative health care database in a single institution, we identified patients diagnosed with stage III or IV primary epithelial ovarian, tubal, and peritoneal cancers with minimal residual disease after primary cytoreductive surgery between 1995 and 2012. Here, we sought to evaluate whether intraperitoneal chemotherapy outperforms intravenous chemotherapy in the presence of competing risks. Unadjusted and multivariable subdistribution hazards models were applied to this database with two types of competing risks (cancer-specific mortality and other-cause mortality) coded to measure the relative effects of intraperitoneal chemotherapy. RESULTS: A total of 1263 patients were recruited as the initial cohort. After propensity score matching, 381 patients in each arm entered into final competing risk analysis. Cumulative incidence estimates for cancer-specific mortality were statistically significantly lower (p = 0.017, Gray test) in patients receiving intraperitoneal chemotherapy (5-year estimates, 34.5%; 95% confidence interval [CI], 29.5-39.6%, and 10-year estimates, 60.7%; 95% CI, 52.2-68.0%) versus intravenous chemotherapy (5-year estimates, 41.3%; 95% CI, 36.2-46.3%, and 10-year estimates, 67.5%, 95% CI, 61.6-72.7%). In subdistribution hazards analysis, for cancer-specific mortality, intraperitoneal chemotherapy outperforms intravenous chemotherapy (Subdistribution hazard ratio, 0.82; 95% CI, 0.70-0.96) after correcting other covariates. CONCLUSIONS: In conclusion, results from this comparative effectiveness study provide supportive evidence for previous published randomized trials that intraperitoneal chemotherapy outperforms intravenous chemotherapy even eliminating the confounding of competing risks. We suggest that implementation of competing risk analysis should be highly considered for the investigation of cancer patients who have medium to long-term follow-up period.

The association between urbanization and rheumatoid arthritis in Taiwan.

OBJECTIVES: To investigate the association between rheumatoid arthritis (RA) and urbanization and compare the medication selection for RA patients in urban vs. rural areas. METHODS: RA patients were identified among 1,000,000 random individuals from a 23-million-person nationwide health insurance database, and controls were matched at a 1 : 10 ratio. Taiwan's 359 townships were grouped into 7 urbanization levels. Geographic region and monthly income were also analyzed. Medication use in the most urbanized and less-urbanized areas were also compared. RESULTS: Rural dwellers had lower odds of having an RA diagnosis. The odds ratio (OR) for level 5 area residents of having an RA diagnosis was 0.62 (95% confidence interval (CI) 0.46 - 0.85; p = 0.002), and they were both 0.76 for level 6 - 7 area residents (95% CI, 0.61 - 0.95 for level 6; p = 0.017 and 0.60 - 0.96 for level 7; p = 0.021) compared to level 1 (the most urban dwellers). The ORs of having a new RA diagnosis were 0.57 (95% CI 0.41 - 0.79, p = 0.001) in eastern Taiwan and 0.33 (95% CI 0.15 - 0.69, p = 0.004) on offshore islands compared to northern Taiwan. No association was found between monthly income and RA. Urban-dwelling RA patients used more tumor necrosis factor-α antagonists (level 1 urbanization; n = 24; 2.3%) than RA patients in less-urbanized areas (level 2 - 7 urbanization n = 30; 1.3%; p = 0.038). CONCLUSION: Results of this study suggested that an RA diagnosis and treatment are associated with urbanization.

Newly diagnosed erectile dysfunction and risk of depression: a population-based 5-year follow-up study in Taiwan.

INTRODUCTION: Depression might increase the risk of erectile dysfunction (ED), and ED might further exacerbate depression. The causal relationship between these two diseases remains controversial. In addition, limited evidence is available regarding the age-dependent and time-dependent effects on the association of depression and ED. AIM: We investigated the hypothesis that ED increases the risk of depression by using a nationwide Taiwanese population-based claims database. In addition, we assessed the age-dependent and time-dependent effects on the association of depression and ED. METHODS: A longitudinal cohort study was conducted to determine the association between patients with ED and depression development during a 5-year follow-up period, using claims data from the Taiwanese National Health Insurance Research Database. MAIN OUTCOME MEASURES: The study cohort comprised patients who were diagnosed with ED during 1997 to 2005 (N = 2,527). For a comparison cohort, 5 age- and sex-matched patients for every patient in the study cohort were selected using random sampling (N = 12,635). All of the patients were followed-up for 5 years from the date of cohort entry to identify the development of depression. RESULTS: The main finding of this study was that patients with ED are at an increased risk of developing depression. The adjusted hazard ratio (AHR) for depression was 2.24-fold higher in the patients with ED than in the comparison cohort (95% confidence interval [CI]: 1.83-2.74; P < 0.001). Regarding the time-dependent effect, the incidence of depression was highest during the first year of follow-up (AHR: 3.03, 95% CI = 2.08-4.40; P < 0.001). CONCLUSIONS: This study demonstrates that patients with ED are at a higher longitudinal risk of developing depression in Asian men, particularly within the first year after the diagnosis of ED.

A nationwide population-based cohort study to identify the correlation between heart failure and the subsequent risk of herpes zoster.

BACKGROUND: The association between heart failure (HF) and herpes zoster has rarely been studied. We investigated the hypothesis that HF may increase the risk of herpes zoster in Taiwan using a nationwide Taiwanese population-based claims database. METHOD: Our study cohort consisted of patients who received a diagnosis of HF in 2001 ~ 2009 (N = 4785). For a comparison cohort, three age- and gender-matched control patients for every patient in the study cohort were selected using random sampling (N = 14,355). All subjects were tracked for 1 year from the date of cohort entry to identify whether or not they had developed herpes zoster. Cox proportional-hazard regressions were performed to evaluate 1-year herpes zoster-free survival rates. RESULTS: The main finding of this study was that patients with HF seemed to be at an increased risk of developing herpes zoster. Of the total patients, 211 patients developed herpes zoster during the 1-year follow-up period, among whom 83 were HF patients and 128 were in the comparison cohort. The adjusted hazard ratio (AHR) of herpes zoster in patients with HF was higher (AHR: 2.07; 95% confidence interval (CI): 1.54 ~ 2.78; p < 0.001) than that of the controls during the 1-year follow-up. Our study also investigated whether HF is a gender-dependent risk factor for herpes zoster. We found that male patients with HF had an increased risk of developing herpes zoster (AHR: 2.30 95% CI: 1.51 ~ 3.50; p < 0.001). CONCLUSIONS: The findings of our population-based study suggest that patients with HF may have an increased risk of herpes zoster. These health associations should be taken into consideration, and further studies should focused on the cost-effectiveness of the herpes zoster vaccine should be designed for HF patients.

The risk of irritable bowel syndrome in patients with endometriosis during a 5-year follow-up: a nationwide population-based cohort study.

PURPOSE: Studies have suggested that endometriosis may coexist with irritable bowel syndrome (IBS). Using a population-based cohort study, we followed subjects for a 5-year period to identify the risk of IBS after a diagnosis of endometriosis. METHODS: This cohort study used the Taiwan National Health Insurance Database as a source of subjects. A total of 6076 patients with endometriosis from 2000 to 2005 were identified. Their data were compared with those of 30,380 age-matched controls without endometriosis who were randomly selected from the same database. All subjects were tracked for 5 years from the date of cohort entry to identify the risk of IBS. The Cox model was used to evaluate the 5-year event occurrence of IBS. RESULTS: Nine hundred twenty-six patients were diagnosed with IBS, including 256 in the case cohort (4.2%) and 670 in the control cohort (2.2%). The Kaplan-Meier survival curves demonstrated significantly lower event-free rates in the case cohort than in the control cohort (P = 0.001). After adjusting for urbanization level, monthly income, residential region and comorbidities, the hazard ratio (HR) within 5 years revealed a 1.79-fold (95% confidence interval [CI] 1.55-2.07) greater risk among the cases than the controls. The HR was higher within the first year of follow-up (HR 1.90, 95% CI 1.42-2.55) and in those women aged 25-34 years (HR 2.17, 95% CI 1.61-2.92). CONCLUSIONS: The risk of IBS among endometriosis patients persisted over 5 years of follow-up. The association detected in this study might have proceeded through shared risk and pathogenic factors.

Increased association between endometriosis and endometrial cancer: a nationwide population-based retrospective cohort study.

OBJECTIVE: Association between endometriosis and ovarian cancer has been well established. Nonetheless, endometriosis may also be associated with endometrial cancer because of shared etiological mechanisms of both estrogen stimulation and chronic inflammation; however, the association between these 2 disorders has rarely been investigated. METHODS: The National Health Insurance Research Databases in Taiwan were retrieved and analyzed. The case cohort consisted of patients with a diagnosis of endometriosis between January 1997 and December 2000 (N = 15,488). For the construction of control cohort, 8 age- and sex-matched control patients for every patient in the case cohort were selected using a random sampling method (n = 123,904). All subjects were tracked for 10 years from the date of entry to identify whether they had developed endometrial cancer. The Cox proportional hazards regression model was used to evaluate 10-year event occurrence of endometrial cancer. RESULTS: During the 10-year follow-up period, 392 participants developed endometrial cancer, with 104 (0.7%) distributed in the case cohort and 288 (0.2%) in the control cohort. Multivariable Cox regression modeling demonstrates a higher risk for developing endometrial cancer in the case cohort than in the control cohort (adjusted hazard ratio [aHR], 2.83; 95% confidence interval [CI], 1.495.35; P < 0.01). Age at diagnosis of endometriosis shows a moderator effect: when 40 years or younger, the risk for developing endometrial cancer was comparable between the case cohort and the control cohort (aHR, 1.42; 95% CI, 0.55-3.70; P = 0.226), whereas when older than 40 years, the risk for developing endometrial cancer was higher in the former group than in the latter group (aHR, 7.08; 95% CI, 2.33-21.55; P = 0.007). CONCLUSIONS: Patients diagnosed with endometriosis may harbor an increased risk for developing endometrial cancer in their later life. Closer monitoring is advised for this patient population.

Osteoporosis and the risk of symptomatic nephrolithiasis: a population-based 5-year follow-up study in Taiwan.

This study estimates the risk of symptomatic nephrolithiasis within 5 years of newly diagnosed osteoporosis in a Taiwan population. This cohort study consisted of patients with a diagnosis of osteoporosis between Jan. 2003 and Dec. 2005 (N = 1634). Four age- and gender- matched patients for every patient in the study cohort were selected using random sampling as the comparison cohort (N = 6536). All patients were tracked for 5 years from the date of cohort entry to identify whether they developed symptomatic nephrolithiasis. Cox proportional hazard regressions were performed to evaluate the 5-year nephrolithiasis-free survival rates. During the 5-year follow-up period, 60 osteoporosis patients (3.7%) and 165 non- osteoporosis patients (2.5%) developed symptomatic nephrolithiasis. The adjusted HR of symptomatic nephrolithiasis was 1.38 times greater risk for patients with osteoporosis than for the comparison cohort (95% confidence interval (CI) 1.03-1.86; P < .05). Osteoporosis is very likely to be an independent risk factor for subsequent diagnosis of symptomatic nephrolithiasis.

Osteoporosis increases subsequent risk of gallstone: a nationwide population-based cohort study in Taiwan.

BACKGROUND: Osteopontin (OPN) is a pro-inflammatory cytokine which is expressed in various tissues. It participates in the bone remodeling process and stimulates bone resorption by osteoclasts. It is also a core protein of cholesterol gallstones. We hypothesized osteoporotic patients might have higher risk in developing gallstones and conducted a population-based study to examine the risk of developing gallstone in osteoporotic patients in Taiwan. METHODS: A total of 1,638 patients diagnosed with osteoporosis between 2003 and 2005 were identified in the National Health Insurance Research Database. A comparison cohort without osteoporosis (n =6,552) was randomly matched to each osteoporosis patient at a ratio of 4: 1 based on age and sex. A Cox proportional-hazards regression analysis was performed to evaluate the 5-year gallstone-free survival rates for the 2 cohorts. RESULTS: During the 5-year follow-up period, 114 and 311 cases of gallstone occurred in the osteoporosis and comparison cohorts, respectively. After adjusting for the confounders, the Cox regression analysis of the risk of gallstone in the osteoporosis and comparison cohorts yielded a hazard ratio of 1.35 (95% confidence interval: 1.07 - 1.69; p < 0 .01). CONCLUSION: Patients with osteoporosis in Taiwan have a higher risk of developing gallstone than the general population.

A mechanistic study on urine retention in d-amphetamine addicts.

Chronic amphetamine intake leads to neurogenic bladder and chronic urinary retention. The mechanism underlying persistent urinary retention is unclear. The pelvic-urethral reflex (PUR) is essential for the urethra to develop sufficient resistance to maintain urine continence, an important function of the urinary system. Recent studies on PUR activities have indicated that repetitive/tetanic stimulation of the pelvic afferent fibers induces spinal reflex potentiation (SRP) in PUR activities, which further increases urinary retention. In this study, results showed that test stimulation (TS, 1/30 Hz) evoked a baseline reflex activity, while repetitive stimulation (RS, 1 Hz) induced reflex potentiation in the external urethral sphincter. Intrathecal d-amphetamine (AMPH, 30 µM) did not but higher AMPH concentration (100 µM) induced SRP in TS-induced reflex activity. H89 (10 µM, a protein kinase A inhibitor), but not chelerythrine chloride (CTC, 10 µM, a protein kinase C inhibitor), prevented the 100 µM AMPH-elicited SRP. At 30 µM, forskolin, an activator of adenylyl cyclase, elicited SRP. The co-administration of 10 µM forskolin and 30 µM AMPH induced SRP in TS-induced reflex activity. These results implied that the repetitive/tetanic stimulation of the pelvic afferent fibers could induce SRP in PUR activities, so that the urethra can produce sufficient resistance and played a significant role in urinary retention. Findings in this study demonstrated that amphetamine could induce bladder dysfunction by triggering protein kinase A activation, and provide a practical basis for the development of treatment for amphetamine-associated urinary retention.

A Chinese herbal medicine, jia-wei-xiao-yao-san, prevents dimethylnitrosamine-induced hepatic fibrosis in rats.

Jia-wei-xiao-yao-san (JWXYS) is a traditional Chinese herbal medicine that is widely used to treat neuropsychological disorders. Only a few of the hepatoprotective effects of JWXYS have been studied. The aim of this study was to investigate the hepatoprotective effects of JWXYS on dimethylnitrosamine- (DMN-) induced chronic hepatitis and hepatic fibrosis in rats and to clarify the mechanism through which JWXYS exerts these effects. After the rats were treated with DMN for 3 weeks, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were significantly elevated, whereas the albumin level decreased. Although DMN was continually administered, after the 3 doses of JWXYS were orally administered, the SGOT and SGPT levels significantly decreased and the albumin level was significantly elevated. In addition, JWXYS treatment prevented liver fibrosis induced by DMN. JWXYS exhibited superoxide-dismutase-like activity and dose-dependently inhibited DMN-induced lipid peroxidation and xanthine oxidase activity in the liver of rats. Our findings suggest that JWXYS exerts antifibrotic effects against DMN-induced chronic hepatic injury. The possible mechanism is at least partially attributable to the ability of JWXYS to inhibit reactive-oxygen-species-induced membrane lipid peroxidation.

Population-based study of the association between urbanization and Kawasaki disease in Taiwan.

Background. It is unclear if the prevalence of Kawasaki disease (KD) correlates with the degree of urbanization. We hypothesized that the prevalence of KD is more pronounced in urban versus rural environments. Methods. The National Health Insurance (NHI) program was implemented in Taiwan in 1995 and covers most of the population (>99%). We used the NHI database to investigate the epidemiological features of KD. A total of 115 diagnosed patients with KD from 1997 to 2010 were included, together with 1,150 matched controls without KD. Chi-square analyses were performed to investigate the difference between modern city and rural environments. Results. Of the 1265 sampled subjects (claims data from 1,000,000 random subjects), the mean age of the KD study group and control group was 2.08 ± 1.66 and 2.08 ± 1.64 years, respectively. After matching for age, sex, and same index date, no statistically significant differences in urbanization level and geographical location of the patients' residence were observed. Conclusion. Urbanization did not appear to be an important effect modifier of Kawasaki disease in Taiwan.

Trends in the incidence of head and neck cancer: A nationwide population-based study.

OBJECTIVE: This study aimed to demonstrate the temporal trend in incidence of head and neck cancer (HNC) in Taiwan. MATERIALS AND METHODS: Patients with a HNC were retrieved from the Taiwan's Health Insurance Database. We identified 16,894 patients aged ≥20 years who had received a first-time diagnosis of cancer of the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, sinonasal, salivary gland or thyroid gland between 2010 and 2018. We calculated the annual incidence rate per 100,000 population, overall, and classified by gender and cancer type. We also used the annual percent change (APC) to characterize trends in head and neck cancer rates over time. RESULTS: The incidence rate showed a gradual decline during this period from 2010 to 2018 with an APC of -2.81% (p < 0.001). Within gender groups, the decline was not statistically significant among females (APC = -1.69, 95% CI = -3.58 âˆ¼ 0.23, p = 0.080). Within cancer types, strikingly high magnitude and statistically significant declines were observed in respect of cancer of the nasopharynx (APC = -7.89%, 95% CI = -9.43%∼-6.31%, p < 0.001), sinonasal cancer (APC = -10.08%, 95% CI = -16.66%∼-2.99%, p = 0.012) and oropharyneal cancer (APC = -9.47%, 95% CI = -15.15%∼-3.42%, p = 0.013) over the study period. In contrast, there was a statistically significant increase in incidence on thyroid cancer over the study period with an APC of 4.75% (95% CI = -2.81%∼6.75%, p < 0.001). CONCLUSIONS: HNCs in Taiwan are showing a decreasing trend, led by the upper respiratory and oropharyngeal cancers. However, there was a concurrent increasing trend of the incidence on thyroid cancer. These trends may be attributable to changing lifestyles and behavioral choices in Taiwan.

Lack of association between CLEC5A gene single-nucleotide polymorphisms and Kawasaki disease in Taiwanese children.

BACKGROUND: Kawasaki disease is characterized by systemic vasculitis of unknown etiology. Previous genetic studies have identified certain candidate genes associated with susceptibility to KD and coronary artery lesions. Host innate immune response factors are involved in modulating the disease outcome. The aim of this study was to investigate CLEC5A (C-type lectin domain family 5) genetic polymorphisms with regards to the susceptibility and outcome of KD. METHODS: A total of 1045 subjects (381 KD patients and 664 controls) were enrolled to identify 4 tagging single-nucleotide polymorphisms (tSNPs) of CLEC5A (rs1285968, rs11770855, rs1285935, rs1285933) by using the TaqMan Allelic Discrimination Assay. The Hardy-Weinberg equilibrium was assessed in cases and controls, and genetic effects were evaluated by the chi-square test. RESULTS: No significant associations were noted between the genotypes and allele frequency of the 4 CLEC5A tSNPs between controls and patients. In the patients, polymorphisms of CLEC5A showed no significant association with coronary artery lesion formation and intravenous immunoglobulin treatment response. CONCLUSIONS: This study showed for the first time that polymorphisms of CLEC5A are not associated with susceptibility to KD, coronary artery lesion formation, and intravenous immunoglobulin treatment response in a Taiwanese population.

DC-SIGN (CD209) promoter -336 A/G (rs4804803) polymorphism associated with susceptibility of Kawasaki disease.

Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. High-dose intravenous immunoglobulin (IVIG) is the most effective therapy for KD to reduce the prevalence of coronary artery lesion (CAL) formation. Recently, the α2, 6 sialylated IgG was reported to interact with a lectin receptor, specific intracellular adhesion molecule-3 grabbing nonintegrin homolog-related 1 (SIGN-R1) in mice and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) in human, and to trigger an anti-inflammatory cascade. This study was conducted to investigate whether the polymorphism of DC-SIGN (CD209) promoter -336 A/G (rs4804803) is responsible for susceptibility and CAL formation in KD patients using Custom TaqMan SNP Genotyping Assays. A total of 521 subjects (278 KD patients and 243 controls) were investigated to identify an SNP of rs4804803, and they were studied and showed a significant association between the genotypes and allele frequency of rs4804803 in control subjects and KD patients (P = 0.004 under the dominant model). However, the promoter variant of DC-SIGN gene was not associated with the occurrence of IVIG resistance, CAL formation in KD. The G allele of DC-SIGN promoter -336 (rs4804803) is a risk allele in the development of KD.

Identification of Druggable Genes for Asthma by Integrated Genomic Network Analysis.

Asthma is a common and heterogeneous disease characterized by chronic airway inflammation. Currently, the two main types of asthma medicines are inhaled corticosteroids and long-acting ß2-adrenoceptor agonists (LABAs). In addition, biological drugs provide another therapeutic option, especially for patients with severe asthma. However, these drugs were less effective in preventing severe asthma exacerbation, and other drug options are still limited. Herein, we extracted asthma-associated single nucleotide polymorphisms (SNPs) from the genome-wide association studies (GWAS) and phenome-wide association studies (PheWAS) catalog and prioritized candidate genes through five functional annotations. Genes enriched in more than two categories were defined as "biological asthma risk genes." Then, DrugBank was used to match target genes with FDA-approved medications and identify candidate drugs for asthma. We discovered 139 biological asthma risk genes and identified 64 drugs targeting 22 of these genes. Seven of them were approved for asthma, including reslizumab, mepolizumab, theophylline, dyphylline, aminophylline, oxtriphylline, and enprofylline. We also found 17 drugs with clinical or preclinical evidence in treating asthma. In addition, eleven of the 40 candidate drugs were further identified as promising asthma therapy. Noteworthy, IL6R is considered a target for asthma drug repurposing based on its high target scores. Through in silico drug repurposing approach, we identified sarilumab and satralizumab as the most promising drug for asthma treatment.

Chronic obstructive pulmonary disease is associated with a higher risk of functional gastrointestinal disorders.

RATIONALE: The association between chronic obstructive pulmonary disease (COPD) and functional gastrointestinal disorders (FGIDs) remains unclear. METHODS: Using Taiwan's National Health Insurance Research Database, we conducted a nationwide population-based study to explore the relationship of COPD and future FGIDs development. The COPD cohort consisted of 4107 patients with COPD between 2000 and 2005. For a comparison cohort, 12,321 age- and gender-matched patients without COPD were randomly selected. The two cohorts were tracked for 5 year and observed for occurrence of FGIDs. The operational definition of COPD in the Korean Health Insurance Review and Assessment Service database was used to validate the results. The validation study confirmed the accuracy of definitions of COPD (83.5% sensitivity). RESULTS: The adjusted hazard ratios (aHR) of FGIDs in patients with COPD was higher (aHR: 1.63; 95% confidence interval (CI): 1.45-1.83; P < .001) than that of the comparison patients. In our secondary analysis in which FGIDs was divided into gastroesophageal reflux disease, irritable bowel syndrome and functional dyspepsia. Patients with COPD also had higher risk for all three subtypes of FGIDs: irritable bowel syndrome (aHR: 1.55; 95% confidence interval (CI): 1.27-1.90; P < .001), gastroesophageal reflux disease (aHR: 2.10; 95% confidence interval (CI): 1.76-2.49; P < .001), and functional dyspepsia (aHR: 1.34; 95% confidence interval (CI): 1.11-1.62; P = .003). The results in validated COPD group were consistent with those in unvalidated COPD group. CONCLUSION: Patients with COPD appeared to be at higher risk for future FGIDs.

A polymorphism of the ORAI1 gene is associated with the risk and recurrence of calcium nephrolithiasis.

PURPOSE: Store-operated calcium entry has been considered an important factor to regulate inflammatory reactions in nonexcitable cells. However, the effects of genetic polymorphisms of ORAI1, a main component of store-operated calcium channels, on nephrolithiasis and stone recurrence remain unclear. We investigated the association between calcium containing nephrolithiasis and genetic variants of ORAI1 gene in Taiwanese patients. MATERIALS AND METHODS: A case-control study was performed in 136 patients with nephrolithiasis and 500 controls. Five tagging single nucleotide polymorphisms of ORAI1 were selected for genotyping. ORAI1 genotypes were determined by TaqMan® assay. Hardy-Weinberg equilibrium in cases and controls was assessed, and genetic effects were evaluated by the chi-square test and sliding window haplotype analysis. Subset analysis was done according to family history. RESULTS: Two single nucleotide polymorphisms (rs12313273 and rs6486795) of the ORAI1 gene were associated with the risk of nephrolithiasis. The C allele carrier for rs12313273 was strongly related to recurrent stone forming in patients. On sliding window analysis the results of the 2 (rs12313273 and rs7135617) and the 3 (rs12313273, rs7135617 and rs6486795) single nucleotide polymorphism haplotypes had more significant effects on the risk of nephrolithiasis than the single nucleotide polymorphism rs12313273. CONCLUSIONS: To our knowledge this is the first study identifying the novel polymorphisms of the ORAI1 gene, which may predispose to the risk of calcium nephrolithiasis and disease recurrence.

CASP3 gene single-nucleotide polymorphism (rs72689236) and Kawasaki disease in Taiwanese children.

Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. A study from Japan reported that G to A substitution of a single-nucleotide polymorphism (SNP) located in the 5'-untranslated region of caspase 3 (CASP3) (rs72689236), which was associated with nuclear factor of activated T cell-mediated T-cell activation, is responsible for susceptibility to KD. This study was conducted to investigate whether the polymorphism of CASP3 is responsible for susceptibility and coronary artery lesion (CAL) formation in KD in the Taiwanese population. A total of 1092 subjects (341 KD patients and 751 controls) were investigated to identify an SNP of rs72689236 using Invader assays (Third Wave Technologies). Our data provided a borderline significant association between the genotypes and allele frequency of rs72689236 in control subjects and KD patients (P=0.0535 under the dominant model; P=0.0575 under the allelic model). The A allele of rs72689236 in KD patients and in patients with CAL and intravenous immunoglobulin resistance was seen in a higher frequency. Importantly, a significant association was obtained between rs72689236 and KD patients with aneurysm formation (P=0.009, under the recessive model). The A allele of rs72689236 is very likely to be a risk allele in the development of aneurysm in patients with KD.