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ObjectiveThe aim of the study is to investigate the effects of icodextrin on the risks of death, technique failure and the first episode of peritonitis in peritoneal dialysis (PD) patients.MethodsFrom medical records of a medical center in Taiwan, a total of 725 newly diagnosed end-stage kidney disease patients receiving PD for at least 90 days from January 1, 2007 to December 31, 2018 were identified. These patients were grouped as 190 icodextrin users and 535 non-users. Users were defined as utilization of icodextrin for ≥ 50% of their PD duration. The use of icodextrin was considered a time-varying exposure in the Cox proportional hazard model. The risks of death, technique failure and the first episode of peritonitis were compared between two cohorts by the end of 2018.ResultsCompared to the non-users, the icodextrin users had significant lower risks of mortality (6.5 vs.7.2 per 100 person-years; adjusted HR = 0.62, 95% CI = 0.42-0.91) and technique failure (12.7 vs. 15.2 per 100 person-years; adjusted HR = 0.61, 95% CI = 0.47-0.81), and the first peritonitis episode (5.0 vs. 17.0 per 100 person-years; adjusted HR = 0.22, 95% CI = 0.14-0.35). The risk of peritonitis reduced further in icodextrin users with diabetes and with cardiovascular disease.ConclusionIcodextrin was associated with lower risks of mortality, technique failure, and the first episode of peritonitis.

ObjectiveThis study evaluated short-term (1-month) and long-term (1-year) mortality risks associated with the glomerular filtration rate (eGFR) on admission for patients with intracerebral hemorrhage.MethodsFrom the Taiwan Stroke Registry data from April 2006 to December 2016, we identified and stratified patients with intracerebral hemorrhage into five subgroups by the eGFR level on admission: ≥90, 60-89, 30-59, 15-29, and ResultsBoth the 1-month and 1-year mortality rates progressively increased with the decrease in eGFR levels. The 1-month mortality rate in patients with eGFR < 15 mL/min/1.73 m2 or on dialysis was approximately 5.5-fold greater than that in patients with eGFR ≥ 90 mL/min/1.73 m2 (8.31 versus 1.50 per 1000 person-days), with an adjusted hazard ratio (HR) of 4.59 [95% confidence interval (CI) = 2.71-7.78]. Similarly, the 1-year mortality in patients with eGFR < 15 mL/min/1.73 m2 or on dialysis was 7.5 times that in patients with eGFR ≥ 90 mL/min/1.73 m2 (2.34 versus 0.31 per 1000 person-days), with an adjusted HR of 4.54 (95% CI 2.95-6.98).ConclusionImpairment of renal function is an independent risk factor for mortality in patients with intracerebral hemorrhage in a gradual way. The eGFR level is a prognostic indicator for patients with intracerebral hemorrhage.

BackgroundThis study investigated risks of mortality from and morbidity (emergency room visits (ERVs) and outpatient visits) of asthma and chronic obstructive pulmonary disease (COPD) associated with extreme temperatures, fine particulate matter (PM2.5), and ozone (O3) by sex, and age, from 2005 to 2016 in 6 metropolitan cities in Taiwan.MethodsThe distributed lag non-linear model was employed to assess age (0-18, 19-39, 40-64, and 65 years and above), sex-cause-specific deaths, ERVs, and outpatient visits associated with extreme high (99th percentile) and low (5th percentile) temperatures and PM2.5 and O3 concentrations at 90th percentile. Random-effects meta-analysis was adopted to investigate cause-specific pooled relative risk (RR) and 95% confidence intervals (CI) for the whole studied areas.ResultsOnly the mortality risk of COPD in the elderly men was significantly associated with the extreme low temperatures. Exposure to the 90th percentile PM2.5 was associated with outpatient visits for asthma in 0-18 years old boys [RR = 1.15 (95% CI: 1.09-1.22)]. Meanwhile, significant elevation of ERVs of asthma for females aged 40-64 years was associated with exposure to ozone, with the highest RR of 1.21 (95% CI: 1.05-1.39).ConclusionsThis study identified vulnerable subpopulations who were at risk to extreme events associated with ambient environments deserving further evaluation for adaptation.

BACKGROUND:Twin infants are likely at great risk for ROP, but studies reported conflicting findings and population studies examining the risk of retinopathy of prematurity (ROP) in twins is limited. We aimed to evaluate the ROP risk in the cohort of one of twins, comparing to singletons. MATERIAL AND METHODS:Using insurance claims data of a half of children in Taiwan ages 18 and less, we established a twin cohort (N = 27830) born in 1998-2009 and a randomly selected singleton cohort (N = 111080) frequency matched by sex, birth year, residential area and parental occupation and followed up to 2012 years. RESULTS:The overall incidence rate of ROP was 13.6-fold greater in the twin cohort than in the singleton cohort (35.1 vs. 2.58 per 10,000 person-years; adjusted HR = 13.4, 95% CI = 11.7-15.3; p

ObjectivesOur objectives are to examine whether patients with fibromyalgia (FM) present an increased risk of hearing loss (HL) compared with those without FM and to explore the relationship between comorbidities/drugs and development of HL in patients with FM. Furthermore, we investigated the incidence rate of different types of HL and the joint effects for HL with FM and comorbidities.MethodsThis population-based retrospective cohort study included patients with new-onset FM from 2000 to 2002 (the FM group) and age- and sex-matched randomized patients without FM (the non-FM group) from Taiwan's National Health Insurance Research Database. Patients were followed up from baseline (3 months after FM diagnosis) until death, withdrawal, HL development, or December 31, 2013. The primary outcome was the risk of HL, which was assessed using Cox proportional-hazards analysis.ResultsThe overall HL risk in the FM group was 1.46-fold (95% confidence interval [CI]: 1.38-1.55) higher than that in the non-FM group after adjustment for sex, age, and comorbidities (p < 0.0001). Patients with FM had significantly greater sensorineural HL (adjusted hazard ratio = 1.46, 95% CI: 1.37-1.56) than those without FM. Patients with FM having comorbidities of diabetes, hyperlipidemia, depression, and Meniere's disease had a higher risk of HL than those without FM.ConclusionOur findings support the notion that FM influences HL and is in line with the hypothesis that the FM mechanism is related to a central nervous system abnormality in sensory processing. Health care professionals should provide appropriate screening for the risk of HL and prevention and counseling methods for patients with FM.

Exposure to air pollutants is known to have adverse effects on human health; however, little is known about the association between hydrocarbons in air and an ischemic stroke (IS) event. We investigated whether long-term exposure to airborne hydrocarbons, including volatile organic compounds, increased IS risk. This retrospective cohort study included 283,666 people aged 40 years or older in Taiwan. Cox proportional hazards regression analysis was used to fit single- and multiple-pollutant models for two targeted pollutants, total hydrocarbons (THC) and nonmethane hydrocarbons (NMHC), and estimated the risk of IS. Before controlling for multiple pollutants, hazard ratios (HRs) of IS with 95% confidence intervals for the overall population were 2.69 (2.64-2.74) at 0.16-ppm increase in THC and 1.62 (1.59-1.66) at 0.11-ppm increase in NMHC. For the multiple-pollutant models controlling for PM2.5, the adjusted HR was 3.64 (3.56-3.72) for THC and 2.21 (2.16-2.26) for NMHC. Our findings suggest that long-term exposure to THC and NMHC may be a risk factor for IS development.

This study aimed to investigate whether long-term exposure to airborne hydrocarbons, including volatile organic compounds, increases the risk of developing retinal vein occlusion (RVO) among the population of Taiwan. A retrospective cohort study involving 855,297 people was conducted. Cox proportional hazards regression analysis fitted the multiple pollutant models for two targeted pollutants, including total hydrocarbons (THC), nonmethane hydrocarbons (NMHC) were used, and the risk of RVO was estimated. The chi-squared test and one-way analysis of variance were used to test differences in demographics and comorbidity distribution among tertiles of the targeted pollutants. Before controlling for multiple pollutants, hazard ratios for the overall population were 19.88 (95% CI: 17.56-22.50) at 0.51-ppm increases in THC and 4.33 (95% CI: 3.97-4.73) at 0.27-ppm increases in NMHC. The highest adjusted hazard ratios for different multiple pollutant models of each targeted pollutant were statistically significant (all p values were ≤0.05) for all patients at 29.67 (95% CI: 25.57-34.42) for THC and 16.24 (95% CI: 14.14-18.65) for NMHC. Our findings suggest that long-term exposure to THC and NMHC contribute to RVO development.

BackgroundDysmenorrhea and stroke are health problems affecting women worldwide in their day-to-day lives; however, there is limited knowledge of the stroke risk in women with dysmenorrhea, and there have been no studies assessing the specific distribution of stroke subtypes. This case-control study assessed stroke subtypes by age and the role of comorbidities in women with dysmenorrhea.Methods and findingsData obtained between 1997 and 2013 from Taiwan's health insurance database identified 514 stroke cases and 31,201 non-stroke controls in women with dysmenorrhea aged 15-49 years. Proportional distributions of subtypes and odds ratios (ORs) of stroke associated with comorbidities by age and subtype were measured. We found that the stroke risk in dysmenorrheal patients increased with age, and that hypertension was nine-fold more prevalent in the stroke cases than in the controls and was associated with an adjusted OR of 4.53 (95% confidence interval (CI) = 3.46-5.92) for all stroke cases. Moreover, the proportion of hemorrhagic stroke was greater than that of ischemic stroke in younger dysmenorrheal patients between 15-24 years old (50.5% vs. 11.4%), whereas this was reversed in those aged 30-49 years old (16.1% vs. 21.0%). Overall, 25.3% of the stroke cases consisted of transient cerebral ischemia and 31.3% were other acute but ill-defined cerebrovascular diseases, in which the prevalence increased with age for both types of strokes. Hypertension was the comorbidity with the highest OR associated with each subtype stroke; diabetes, hyperlipidemia, arrhythmia, and thyroid disease were also comorbidities that were significantly associated with ill-defined cerebrovascular diseases.ConclusionsThe stroke type varies by age in dysmenorrheal patients, and hypertension is the most important comorbidity associated with all types of stroke; therefore, more attention for stroke prevention must be paid to women with dysmenorrhea, particularly when combined with comorbidities.

[This corrects the article DOI: 10.1371/journal.pone.0128461.].

As reported by the Taiwan Cancer Registry in 2013 squamous cell carcinoma of head and neck cancer (HNSCC) was the sixth most frequently diagnosed cancer and the 5th most common cause of cancer related death and its incidence and mortality rate is still rising. The co-occurrence of HNSCC and secondary primary cancer (SPC) and the chemopreventive effect of aspirin on certain malignancies had been reported. Therefore we conducted this national study to investigate the use of aspirin associated with risk reduction of secondary primary cancer for patients with head and neck cancer in Taiwan. We searched the Registry for Catastrophic Illness in the National Health Insurance Research Database (NHIRD) for 18,234 patients (3,576 aspirin users and 14,667 non-aspirin users) diagnosed with HNSCC during 2000-2005. The SPC incidence density during follow-up in 2000-2011 was compared between the groups. For HNSCC patients, aspirin use after diagnosis was significantly associated with SPC risk reduction by 25% (adjusted HR, 0.75; 95% CI, 0.63-0.89; p = 0.001) after multivariate analysis. In the subgroup analysis, we found that esophageal cancer and stomach cancer incidence were significantly reduced after aspirin use (adjusted HR, 0.60; 95% CI, 0.41-0.90; p = 0.01 for esophageal cancer; adjusted HR, 0.27; 95% CI, 0.08-0.87; p = 0.03 for stomach cancer). Aspirin use for 1-3 years was associated with SPC risk reduction by 35% (adjusted HR, 0.65; 95% CI, 0.49-0.87; p = 0.003). SPC risk reduction extended continuously for more than 3 years of follow up (adjusted HR, 0.72; 95% CI, 0.53-0.98; p = 0.030). Our data shows aspirin use was associated with reduced SPC incidence for HNSCC patients, attributed mainly to reduced risk of esophageal and stomach cancer.

BACKGROUND:This study evaluated risks of emergency room visit (ERV) for out-of-hospital cardiac arrest (OHCA) in 2005-2011, among patients with cardiologic and metabolic syndromes (CMS), in association with ambient environments. METHODS:Pooled and area-specific weather related cumulative six-day (lags 0 to 5) relative risks (RRs) and confidence intervals (CIs) of ERV for OHCA were evaluated for CMS cases, using distributed lag nonlinear models and multivariate meta-analytical second-stage model in association with the daily average temperatures and daily concentrations of air pollutants. RESULTS:ERV risk increased as average temperature dropped to

BACKGROUND:Studies investigating the fracture risk in patients with chronic osteomyelitis (COM) limited to case reports. This study evaluated the association between COM and subsequent fracture risk using population-based data. METHODS:A subset claims data of the Taiwan National Health Insurance was used to identify 7,147 patients with COM newly diagnosed in 1999-2005 without fracture history and 28,588 general population controls, frequency matched by sex, age and diagnosis date. The incident fractures was measured by the end of 2013. RESULTS:The incidence density of fracture was 1.94-fold greater in the COM cohort than in controls (21.5 vs. 11.1 per 1000 person-years), with the adjusted hazard ratio (HR) of 1.81 (95% CI: 1.67-1.95) for COM patients compared to controls after controlling for sex, age, and comorbidities of diabetes, osteoporosis, depression and end-stage renal disease in Cox proportional hazards regression. The fracture risk increased with age and women were at greater risk than men. The fracture incidence increased substantially in those with osteoporosis, 40.2 per 1000 person-years in COM patients. Site specific analysis showed a higher portion of incident fractures for lower limbs, 52.7% in COM cohort and 46.3% in controls. CONCLUSION:Findings in this 15-year follow-up observation support our hypothesis that patients with COM are at an elevated risk of subsequent fracture. COM patients and the elderly deserve adequate consultation and awareness for fracture prevention.

The relationship between cholesterol level and hemorrhagic stroke is inconclusive. We hypothesized that low cholesterol levels may have association with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes. This study used data obtained from a multi-center stroke registry program in Taiwan. We categorized acute spontaneous ICH patients, based on their baseline levels of total cholesterol (TC) measured at admission, into 3 groups with 200 mg/dL of TC. We evaluated risk of having initial stroke severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality) after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5±14.2 years; 64.2% men) were included in this study and 854 (34.9%) of them had baseline TC 15), with an adjusted odds ratio [aOR] of 1.80; 95% confidence interval [CI], 1.41-2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11-1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL and body mass index (BMI)

Inflammatory bowel diseases (IBD) and cholecystectomy are associated with the risk of colorectal cancer (CRC). Our aim was to determine the association between cholecystectomy and the CRC risk in IBD.We first obtained the Taiwan National Health Insurance Research Database (NHRID), which contains information on approximately 24.7 million insured individuals. A cohort study was conducted using the data from the NHIRD, and included cohort patients with IBD who had experienced a cholecystectomy between the years 1998 and 2010. The non-cholecystectomy cohort comprised the remaining IBD patients who had not undergone a cholecystectomy. Multivariate Cox proportional hazard regression analysis was used to determine the effects cholecystectomy have on the risks of developing CRC, as shown by Hazard Ratios (HRs) with 95% confidence intervals (CIs).The incidence rate of CRC among IBD patients who had undergone a cholecystectomy (n = 525) was 1.75 per 1,000 person-years, compared to 1.41 per 1,000 person-years among IBD patients who had not had a cholecystectomy (n = 525). The adjusted HRs for CRC was found to be 0.76 (95% CI 0.25-2.32) for IBD patients having received a cholecystectomy, after adjusting for age, gender, and comorbidities. By type of IBD, neither ulcerative colitis nor Crohn's diseases are associated with CRC after a cholecystectomy adjusted HR (2.78 [95% CI 0.54-14.3]) and (0.13 [95% CI 0.01-1.49]).In Taiwan, cholecystectomies are not associated with a risk of CRC in patients with IBD.

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

[This corrects the article DOI: 10.1371/journal.pone.0113579.].

The association between Sjögren's syndrome (SS) and chronic hepatitis virus infection is inconclusive. Hepatitis B (HBV) and hepatitis C virus (HCV) infections are highly prevalent in Taiwan. We used a population-based case-control study to evaluate the associations between SS and HBV and HCV infections.We identified 9,629 SS patients without other concomitant autoimmune diseases and 38,516 sex- and age-matched controls without SS from the Taiwan National Health Insurance claims data between 2000 and 2011. We utilized multivariate logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between SS and HBV and HCV infections. Sex- and age-specific (

[This corrects the article DOI: 10.1371/journal.pone.0161958.].

BACKGROUND:There is a demonstrated association between asthma and irritable bowel syndrome (IBS). In this study, we examined the bidirectional association between asthma and IBS using a nationwide database. METHODS:We conducted two retrospective cohort studies using data obtained from the National Health Insurance of Taiwan. Study 1 included 29,648 asthma patients newly diagnosed between 2000 and 2010. Study 2 included 29,875 IBS patient newly diagnosed between 2000 and 2010. For each study, four subjects without asthma and IBS were selected, respectively, frequency-matched by sex, age, and the diagnosis date. All four cohorts were followed up until the end of 2011 to estimate incident IBS for Study 1 and incident asthma for study 2. Adjusted hazard ratios (aHRs) were estimated using the Cox proportional hazards model after controlling for sex, age and comorbidities. RESULTS:The incidence of IBS was 1.89 times higher in the asthma cohort than in the comparison cohort (8.26 vs. 4.36 per 1,000 person-years), with an aHR of 1.57 [95% confidence interval (CI) = 1.47-1.68]. The aHRs remained significant in all subgroups measured by sex, age and the presence of comorbidities. In contrast, the incidence of asthma was 1.76 times higher in the IBS cohort than the comparison cohort (7.09 vs. 4.03 per 1,000 person-years), with an aHR of 1.54 (95% CI = 1.44-1.64). Similarly, aHRs remained significant in all subgroups measured by sex, age and the presence of comorbidities. CONCLUSION:The present study suggests a bidirectional association between asthma and IBS. Atopy could be a shared pathophysiology underlying this association, deserving a further investigation.

Cancer risk after appendectomy in patients with appendicitis remains unclear. This study examined the role of appendicitis as an early manifestation harbingering the distant malignancy.From the insurance claims data of Taiwan, we identified a cohort of 130,374 patients newly received appendectomy from 2000-2009, without cancer diagnosis. A comparison cohort of 260,746 persons without appendectomy and cancer was selected from the same database, frequency matched by age, sex, comorbidity and index year. We monitored subsequent cancers with a12-month follow-up.Over all, 1406 and 616 cancer cases were identified in the appendectomy cohort and comparisons, respectively, with all cancers incidence rate 4.64-fold higher in the appendectomy cohort (9.06 vs. 1.96 per 1000 person-months). Digestive and female genital organs harbored 80.9% of cancer cases in the appendectomy cohort. The Cox model measured site-specific hazard ratio (HR) was the highest for female genital cancers (23.3), followed by cancers of colorectum (14.7), small intestine (10.1), pancreas (7.40), lymphoma (5.89) and urinary system (4.50), all significant at 0.001 level. The HR of all cancers decreased from 13.7 within 3 months after appendectomy to 1.37 in 7-12 months after the surgery. In general, relative to the comparison cohort, younger appendectomy patients tended to have a higher HR than older patients.The high incident cancers identified soon after appendectomy suggest the acute appendicitis is the early sign of distant metastatic malignancy. The risk of colorectal cancer, female genital cancer and haemopoietic malignancy deserve attention.

Diabetes is a common diseases and a major problem worldwide. Diabetic osteopathy might be elevated in diabetic patients and is usually caused by bone fracture. Several diabetes medications, such as thiazolidinediones (TZDs), could lead to increased risks of fracture.We used the nationwide database to identified 32466 patients who had developed type 2 diabetes from 2000 to 2010 as the diabetic cohort and, from that group, we selected 3427 diabetic patients who had developed bone fracture to survey the possible risk factors, includng commonly used diabetes medication.We found that TZDs might present increased risks for fracture in patients who used it for an extended period (7 to 730 days before the index date), especially in female patients younger than 64 years old, for whom the risk was elevated from a 1.74- to a 2.58-fold odds ratio.We recommend that clinics follow up with non-osteoporotic female patients younger than 64 years old who are using TZDs, to avoid the associated risks of fracture.

The appendix may modulate colon microbiota and bowel inflammation. We investigated whether appendectomy alters colorectal cancer risk.We identified a cohort of 75,979 patients who underwent appendectomy between 1997 and 1999 based on the insurance claims of Taiwan. A comparison cohort of 303,640 persons without appendectomy was selected randomly, frequency matched by age, sex, comorbidity and entry year was also selected. We monitored subsequent colorectal cancer development in both cohorts.The overall colorectal cancer incidence was 14% higher in the appendectomy patients than in the comparison cohort (p

Organophosphorus pesticides are widely used throughout the world. Because of their ease of availability, organophosphorus compounds are commonly used for self-poisoning in developing countries. The acute effects of exposure to organophosphorus pesticides are well known, but the chronic effects are unclear. Recent studies suggest that abnormalities of the central and peripheral nervous systems persisted for up to 5 years after acute poisoning due to a single large dose of organophosphates (OPs). However, the long-term effects on cardiovascular diseases are poorly understood.An OPs-exposed cohort (N = 7,561) and an age- and gender-matched control cohort (N = 30,244), both identified from the National Health Insurance Research Database, were compared. We utilized the multivariable Cox proportional model to estimate the risks of developing arrhythmia, coronary artery disease (CAD) and congestive heart failure (CHF). The patients with acute poisoning from OPs had higher incidence rates of arrhythmia (5.89 vs. 3.61 per 1,000 person-years), CAD (9.10 vs. 6.88 per 1,000 person-years), and CHF (3.89 vs. 2.98 per 1,000 person-years) compared with that of the non-OPs poisoning cohort, with a crude subhazard ratio (SHR) of 1.40, 1.13, and 1.12, respectively. Additionally, a significantly higher risk of arrhythmia was observed in the OPs poisoning cohort (adjusted SHR = 1.25) compared with the non-OPs poisoning cohort, particularly in male patients (adjusted SHR = 1.33) and those under 49 years of age (adjusted SHR = 3.16). After accounting for the competing risks of death, there was a higher risk of arrhythmia and CAD during a three year follow-up period (adjusted SHR = 1.50 for arrhythmia; adjusted SHR = 1.10 for CAD). We also found an adjusted SHR of 1.36 associated with developing CHF after 6 years of follow-up for OPs poisoning cohort.Acute OPs poisoning may continuously impact human health through mechanisms that are unclear. Any supportive measurements that could contribute to a reduction in the risk of heart disease may be beneficial in cases of OPs poisoning survivors.

The relationship between asthma and ankylosing spondylitis (AS) is controversial. We examined the risk of asthma among AS patients in a nationwide population.We conducted a retrospective cohort study using data from the National Health Insurance (NHI) system of Taiwan. The cohort included 5,974 patients newly diagnosed with AS from 2000 to 2010. The date of diagnosis was defined as the index date. A 4-fold of general population without AS was randomly selected frequency matched by age, gender and the index year. The occurrence and hazard ratio (HR) of asthma were estimated by the end of 2011.The overall incidence of asthma was 1.74 folds greater in the AS cohort than in the non-AS cohort (8.26 versus 4.74 per 1000 person-years) with a multivariable Cox method measured adjusted HR of 1.54 (95% confidence interval (CI), 1.34-1.76). The adjusted HR of asthma associated with AS was higher in women (1.59; 95% CI, 1.33-1.90), those aged 50-64 years (1.66; 95% CI, 1.31-2.09), or those without comorbidities (1.82; 95% CI, 1.54-2.13).Patients with AS are at a higher risk of developing asthma than the general population, regardless of gender and age. The pathophysiology needs further investigation.

BACKGROUND:There are several publications reported that obstructive sleep apnea (OSA) was associated with asthma. However, large-scaled, population-based cohort study has been limited. We aimed to examine the risk of OSA among adult patients with asthma in an Asian population. METHODS:We conducted a retrospective cohort study using data from the National Health Insurance (NHI) of Taiwan. The asthma cohort included 38,840 newly diagnosed patients between 2000 and 2010. The date of diagnosis was defined as the index date. Each patient was randomly matched with four people without asthma according to gender, age, and the index year as the comparison cohort. The occurrence of OSA was followed up until the end of 2011. The risk of OSA was estimated using the Cox proportional hazard model after adjusting for gender, age, and comorbidities. RESULTS:The overall incidence of OSA was 2.51-fold greater in the asthma cohort than in the comparison cohort (12.1 versus 4.84 per 1000 person-years). Compared to non-asthma subjects, the adjusted hazard ratio (aHR) of OSA increased to 1.78 for asthma patients with one or less annual emergency room (ER) visit, and 23.8 for those who visited ER more than once per year. In addition, aHR in patients with inhaled steroid treatment compared to those without steroid treatment was 1.33 (95% CI = 1.01-1.76). CONCLUSION:Patients with asthma have a significantly higher risk of developing OSA than the general population. The results suggest that the risk of OSA is proportional to asthma control and patients with inhaled steroid treatment have a higher risk for OSA than those without steroid treatment.

To determine the nationwide incidence of non-traumatic subconjunctival hemorrhage (NTSCH) in Taiwan from 2000-2011 and to analyze the risk factors for NTSCH using a case-control analysis.This is a population-based cohort administrative database study. Randomly selected 1,000,000 residents from the Taiwan National Health Insurance Research Database in 2000 and followed for 12 years to determine the population incidence of NTSCH. Individuals with the first diagnosis of subconjunctival hemorrhage were identified by the corresponding International Classification of Diseases code (ICD) 372.72. Traumatic subconjunctival hemorrhages (ICD-9 codes 921, 871, 850-854 and 959.01) were excluded. The association of NTSCH with various demographic factors, comorbidities and use of medications was studied by a population based case-control analysis using data of 2008-2011.A total of 67,720 patients with a first-time diagnosis of NTSCH were identified during the 12 years period. The mean annual incidence was 65 per 10,000 individuals (crude incidence) and 60 per 10,000 individuals (age- and sex-standardized incidence). The incidence rate of NTSCH was higher in women than in men, [men-women ratio: 0.80 (95% confidence interval: 0.78-0.81)]. The age-specific incidence decreased from childhood to the group of teenagers, after which it increased to a maximal value of 136.2 per 10,000 people in the age group of 60-69 years. Case-control analysis showed that comorbidities of hypertension, purpura and thrombocytopenia, and the use of aspirin were significantly associated with the risk of NTSCH.This study indicates that NTSCH is a common eye disease that occurs once in 167 individuals in a general East Asian population per year. It occurs more often in women than in men and the age-specific incidence peaked in the age group of 60-69 years. Hypertension, purpura and thrombocytopenia, and the use of aspirin are the major risk factors for NTSCH.

BackgroundPatients with traumatic brain injury (TBI) face increased risk of stroke. Whether acupuncture can help to protect TBI patients from stroke has not previously been studied.MethodsTaiwan's National Health Insurance Research Database was used to conduct a retrospective cohort study of 7409 TBI patients receiving acupuncture treatment and 29,636 propensity-score-matched TBI patients without acupuncture treatment in 2000-2008 as controls. Both TBI cohorts were followed until the end of 2010 and adjusted for immortal time to measure the incidence and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of new-onset stroke in the multivariable Cox proportional hazard models.ResultsTBI patients with acupuncture treatment (4.9 per 1000 person-years) had a lower incidence of stroke compared with those without acupuncture treatment (7.5 per 1000 person-years), with a HR of 0.59 (95% CI = 0.50-0.69) after adjustment for sociodemographics, coexisting medical conditions and medications. The association between acupuncture treatment and stroke risk was investigated by sex and age group (20-44, 45-64, and ≥65 years). The probability curve with log-rank test showed that TBI patients receiving acupuncture treatment had a lower probability of stroke than those without acupuncture treatment during the follow-up period (pConclusionPatients with TBI receiving acupuncture treatment show decreased risk of stroke compared with those without acupuncture treatment. However, this study was limited by lack of information regarding lifestyles, biochemical profiles, TBI severity, and acupuncture points used in treatments.

BACKGROUND: Few studies have examined the association of rheumatoid arthritis (RA) with nontuberculosis mycobacterium (NTM) disease and pulmonary tuberculosis (PTB). METHODS: We identified 29 131 patients with RA from the catastrophic illness registry who were diagnosed from 1998-2008; 116 524 patients without RA from inpatient data files were randomly frequency matched according to sex, age, and index year and used as a comparison group. Both groups were followed-up until the end of 2010 to measure the incidence of NTM disease and active PTB. We analyzed the risk of NTM disease and active PTB using the Cox proportional hazards regression models, controlling for sex, age, and Charlson comorbidity index (CCI). RESULTS: The incidence of NTM disease was 4.22 times greater in the RA group than in the non-RA group (1.91 vs 0.45 per 10,000 person-years). The incidence of PTB was 2.99 times greater in the RA group than in the non-RA group (25.3 vs 8.46 per 10,000 person-years). After adjusting for age, sex, and CCI, the adjusted hazard ratios (HRs) of NTM disease and active PTB for the RA group were 4.17 (95% CI = 2.61-6.65) and 2.87 (95% CI = 2.55-3.23), respectively, compared with the non-RA group. In the first 2 years of follow-up, the RA group yielded corresponding adjusted HRs of 4.98 and 3.39 compared with the non-RA group. The follow-up time-specific RA group to the non-RA group HR of both the NTM disease and active PTB varied. CONCLUSION: This study can serve as a reference for clinical physicians to increase awareness regarding the detection of NTM disease and active PTB in RA patients among the any stage of the clinical course even without CCI.

The association between chronic hepatitis virus infection and rheumatoid arthritis (RA) remains debatable. This nationwide population-based cohort study assessed the risk of RA among patients with a chronic infection of hepatitis B and/or C virus.We used data extracted from the claims of 1,000,000 randomly sampled individuals covered under the Taiwan National Health Insurance program. Among the 49,892 persons identified in 2000-2010 with chronic hepatitis virus infection, 35,652 had chronic HBV infection alone, 10,253 had chronic HCV infection alone, and 3,987 had chronic HBV/HCV dual infections. The comparison cohort comprised 199,568 persons matched on sex, age and calendar year without chronic hepatitis virus infection. All study participants were free of RA at baseline and traced through 2011 with new RA cases identified.After adjusting for covariates, chronic HCV infection alone was significantly associated with an increased risk for RA (hazard ratio (HR) = 2.03, 95% confidence interval (CI) = 1.27-3.22). The increased risk for RA among participants with chronic HCV infection remained significant after restricting the analysis to those who were prescribed disease-modifying anti-rheumatic drugs. The corresponding HR for the overall sample was 1.89 (95% CI = 1.15-3.11). However, HBV carriers did not appear to be at a significantly higher risk for RA.Our data imply that chronic HCV infection is associated with RA development.

BACKGROUND AND PURPOSE: Population study on relationship between nontuberculous mycobacterial (NTM) infection and respiratory failure (RF) is limited. This study evaluated the RF risk, including acute respiratory failure (ARF), chronic respiratory failure (CRF) and ARF on CRF, in patients with NTM infection in Taiwan. METHODS: We used the National Health Insurance Research Database of Taiwan to identify 3864 newly diagnosed NTM patients (NTM cohort) from 1999 to 2009, and 15456 non-NTM patients (non-NTM cohort), frequency matched by demographic status for comparison. Incidence and hazard of developing RF were measured by the end of 2010. RESULTS: The incidence rate of RF was 4.31-fold higher in the NTM cohort than in the non-NTM cohort (44.0 vs.10.2 per 1000 person-years), with an adjusted hazard ratio (HR) of 3.11 (95% CI: 2.73-3.54). The cumulative proportional incidence of RF was 10% higher in the NTM cohort than in the non-NTM cohort (P

INTRODUCTION: Our retrospective cohort study investigated the effect of tumor site and stage on the associations between the allelic variants of glutathione S-transferase (GST) and DNA-repair genes and overall survival (OS) in CRC patients treated with 5-fluorouracil (5-FU)-based adjuvant chemotherapy. MATERIAL AND METHODS: We genotyped GSTM1, GSTT1, GSTP1 Ile105Val, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln in 491 CRC patients between 1995 and 2001. A Cox proportional-hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships between the allelic variants and OS. Survival analyses were performed for each allelic variant by using the log-rank test and Kaplan-Meier analysis. RESULTS: The CRC patients with the XPD Gln allelic variants had poorer survival than patients with the Lys/Lys genotype (HR =1.38, 95% CI =1.02-1.87), and rectal cancer patients had the poorest survival among them (HR =1.87, 95% CI =1.18-2.95). A significantly shorter OS was observed among stage II/III colon cancer patients with the XRCC1 Gln allelic variants (HR =1.69, 95% CI =1.06-2.71), compared to those with XRCC1 Arg/Arg genotype. In the combined analysis of the XRCC1 and XPD genes patients with stage II/III tumors, the poorest OS occurred in colon cancer patients with the XRCC1 Gln and XPD Gln allelic variants (HR =2.60, 95% CI =1.19-5.71) and rectal cancer patients with the XRCC1 Arg/Arg and XPD Gln allelic variants (HR =2.77, 95% CI =1.25-6.17). CONCLUSION: The XPD and XRCC1 allelic variants may be prognostic markers for CRC patients receiving 5-FU based chemotherapy. The contributions of the XPD and XRCC1 allelic variants to OS are tumor site- and/or stage-dependent.

PURPOSE: Population-based cohort study on the risk of anxiety and depression in patients with blepharitis is limited. This study evaluated whether blepharitis patients are at a higher risk of anxiety and depression. DESIGN: A retrospective cohort study. METHODS: We used the universal insurance claims data from 1997 to 2010 in Taiwan to identify annually patients with newly diagnosed blepharitis (N = 9764) and without the disease (N = 39056). Incidences, rate ratios (IRR) and hazard ratios (HR) of anxiety and depression were measured for both cohorts by baseline demographic characteristics and comorbidities until the end of 2010. RESULTS: Compared with the non-blepharitis cohort, the blepharitis cohort had higher incidence of anxiety (15.9 vs. 9.5 per 1000 person-years), with an adjusted HR of 1.58 (95% confidence interval (CI) = 1.46-1.70). The incidence of depression was also higher in the blepharitis cohort (7.66 vs. 5.05 per 1000 person-years), with an adjusted HR of 1.42 (95% CI = 1.28-1.58). The blepharitis cohort to the non-blepharitis cohort IRR decreased from 1.73 in the first quartile to 1.32 in the 4(th) quartile for anxiety, and from 1.67 to 1.29 for depression. CONCLUSIONS: Patients with blepharitis are at elevated risks of anxiety and depression. The risk is higher in earlier period after the diagnosis of blepharitis, and declines by time, but remains significantly higher for those with blepharitis than those without blepharitis.

BACKGROUND: Population studies on trends of varicella and herpes zoster (HZ) associated with varicella zoster vaccination and climate is limited. METHODS: This study used insurance claims data to investigate the chronological changes in incident varicella and HZ associated with varicella zoster vaccination. Poisson regression was used to estimate the occurrence of varicella associated with the occurrence of HZ and vice versa by year, season, sex, temperature, and sunny hours. RESULTS: The varicella incidence declined from 7.14 to 0.76 per 1,000 person-years in 2000-2009, whereas the HZ incidence increased from 4.04 to 6.24 per 1,000 person-years. Females tended to have a higher risk than men for HZ (p

BACKGROUND: Western breast cancer survivors have an increased risk of osteoporosis and bone fracture. Breast cancer occurs 10 to 20 years earlier in Asian women than in Western women. We investigated if younger Asian women with breast cancer also have increased risk of fracture. METHODS: We used the universal insurance claims data from 2000 to 2003 to identify 22,076 patients with breast cancer and 88,304 women without cancer, frequency matched with age and index date (the date for a health care visit). The incidence of fracture in both cohorts and the hazard ratios (HRs) of fracture in the cancer cohort were estimated by the end of 2009. RESULTS: The incidence of all types of fracture was higher in the breast cancer cohort than in the comparison cohort (46.72 vs. 42.52 per 10,000 person-years), with adjusted HRs (aHRs) of 1.18 (95% confidence intervals [CI], 1.03-1.35) for hip fractures, 1.12 (95% CI, 0.98-1.28) for forearm fractures and 1.24 (95% CI, 1.04-1.48) for vertebral fractures. The aHRs were significant in both non-traumatic fractures (1.29; 95% CI, 1.11-1.51) and traumatic fractures (1.12; 95% CI, 1.01-1.23). The age-specific aHR was higher for younger breast cancer patients, and was significant for

BACKGROUND: This study presents an evaluation of the bidirectional correlation between attention deficit hyperactivity disorder (ADHD) and epilepsy using 2 cohorts from the same population database. METHODS: We used data from the Taiwan National Health Insurance Research Database to establish 2 separate cohort studies with participants

Studies involving second malignancies in patients with multiple myeloma are limited for the Asian population. Using data from population-based insurance claims, we assessed the risk of developing secondary malignancies after multiple myeloma, in particular hematologic malignancies. A retrospective cohort study was conducted in 3970 patients with newly diagnosed multiple myeloma from the registry of catastrophic illnesses between 1997 and 2009. A total of 15880 subjects without multiple myeloma were randomly selected as comparisons from the insured population, frequency-matched based on gender, age, and the date of diagnosis. The incidence of secondary malignancies was ascertained through cross-referencing with the National Cancer Registry System. The Cox proportional hazards model was used for analyses. The incidence of multiple myeloma in the insured population increased annually. The overall incidence of secondary malignancy was lower in the multiple myeloma cohort than in the comparison cohort (93.6 vs. 104.5 per 10,000 person-years, IRR = 0.90, 95% CI = 0.78-1.04). The incidence of hematologic malignancies was 11-fold greater for multiple myeloma patients (47.2 vs. 4.09 per 10,000 person-years) with an adjusted HR of 13.0 (95% CI = 7.79-21.6) compared with the comparison cohort. The relative risk of secondary malignancy was also strong for myeloid leukemia (21.2 vs. 1.36 per 10,000 person-years). Gender- and age-specific analysis for secondary hematologic malignancies showed that males and patients with multiple myeloma 60 years of age. In conclusion, patients with multiple myeloma, especially younger patients, are at a high risk of hematologic malignancies.

BACKGROUND: Little is known on the effectiveness of influenza vaccine in ESRD patients. This study compared the incidence of hospitalization, morbidity, and mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) between cohorts with and without influenza vaccination. METHODS: We used the insurance claims data from 1998 to 2009 in Taiwan to determine the incidence of these events within one year after influenza vaccination in the vaccine (N = 831) and the non-vaccine (N = 3187) cohorts. The vaccine cohort to the non-vaccine cohort incidence rate ratio and hazard ratio (HR) of morbidities and mortality were measured. RESULTS: The age-specific analysis showed that the elderly in the vaccine cohort had lower hospitalization rate (100.8 vs. 133.9 per 100 person-years), contributing to an overall HR of 0.81 (95% confidence interval (CI) 0.72-0.90). The vaccine cohort also had an adjusted HR of 0.85 [95% CI 0.75-0.96] for heart disease. The corresponding incidence of pneumonia and influenza was 22.4 versus 17.2 per 100 person-years, but with an adjusted HR of 0.80 (95% CI 0.64-1.02). The vaccine cohort had lowered risks than the non-vaccine cohort for intensive care unit (ICU) admission (adjusted HR 0.20, 95% CI 0.12-0.33) and mortality (adjusted HR 0.50, 95% CI 0.41-0.60). The time-dependent Cox model revealed an overall adjusted HR for mortality of 0.30 (95% CI 0.26-0.35) after counting vaccination for multi-years. CONCLUSIONS: ESRD patients with HD receiving the influenza vaccination could have reduced risks of pneumonia/influenza and other morbidities, ICU stay, hospitalization and death, particularly for the elderly.

BACKGROUND: The relationship between hepatitis C virus infection and risk of stroke remains inconsistent. This study evaluates the risk of stroke in association with chronic hepatitis C infection in a longitudinal population-based cohort. METHODS: We identified 4,094 adults newly diagnosed with hepatitis C infection in 2002-2004 from the Taiwan National Health Insurance Research Database. Comparison group consisted of 16,376 adults without hepatitis C infection randomly selected from the same dataset, frequency matched by age and sex. Events of stroke from 2002-2008 were ascertained from medical claims (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM, codes 430-438). Multivariate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for potential associated factors including HCV infection, age, sex, low-income status, urbanization, cessation of cigarette smoking, alcohol-related illness, obesity, history of chronic diseases and medication use. FINDINGS: During 96,752 person-years of follow-up, there were 1981 newly diagnosed stroke cases. The HRs of stroke associated with medical conditions such as hypertension, diabetes and heart disease were 1.48 (95% CI 1.33 to 1.65), 1.23 (95% CI 1.11 to 1.36) and 1.17 (95% CI 1.06 to 1.30), respectively, after adjustment for covariates. The cumulative risk of stroke for people with hepatitis C and without hepatitis C infections was 2.5% and 1.9%, respectively (p

BACKGROUND: Controversy still exists regarding whether alendronate (ALN) use increases the risk of esophageal cancer or breast cancer. METHODS: This paper explores the possible association between the use of oral ALN in osteoporosis patients and subsequent cancer risk using the National Health Insurance (NHI) system database of Taiwan with a Cox proportional-hazard regression analysis. The exposure cohort contained 5,624 osteoporosis patients used ALN and randomly frequency-matched by age and gender of 3 osteoporosis patients without any kind of anti-osteoporosis drugs in the same period. RESULTS: For a dose ≥ 1.0 g/year, the risk of developing overall cancer was significantly higher (hazard ratio: 1.69, 95% confidence ratio: 1.39-2.04) than in osteoporosis patients without any anti-osteoporosis drugs. The risks for developing liver, lung, and prostate cancers and lymphoma were also significantly higher than in the control group. CONCLUSIONS: This population-based retrospective cohort study did not find a relationship between ALN use and either esophageal or breast cancer, but unexpectedly discovered that use of ALN with dose ≥ 1.0 g/year significantly increased risks of overall cancer incidence, as well as liver, lung, and prostate cancers and lymphoma. Further large population-based unbiased studies to enforce our findings are required before any confirmatory conclusion can be made.

OBJECTIVES: The association between viral hepatitis (B and C) and oral cavity cancer has been widely debated. This nationwide, population-based cohort study assessed the subsequent risk of oral cavity cancer among patients with chronic viral hepatitis infection. MATERIALS AND METHODS: Data were retrieved from insurance claims data of 1,000,000 randomly sampled individuals covered under the Taiwan National Health Insurance system. We identified a total of 21,199 adults with chronic viral hepatitis infection (12,369 with HBV alone, 5,311 with HCV alone, and 3,519 with HBV/HCV dual infections) from 2000-2005. Comparison group comprised 84,796 sex- and age-matched subjects without viral hepatitis during the same study period. Incidence and risk of subsequent oral cavity cancer were measured until 2008. RESULTS: The incidence of oral cavity cancers was 2.28-fold higher among patients with HCV alone than non-viral hepatitis group (6.15 versus 2.69 per 10,000 person-years). After adjusting for sociodemographic covariates, HCV alone was significantly associated with an increased risk for oral cavity cancer (hazard ratio (HR) = 1.90, 95% confidence interval (CI) = 1.20-3.02). This positive association was highest among individuals in the 40-49-year age group (HR = 2.57, 95% CI = 1.21-5.46). However, there were no significant associations between HBV alone or HBV/HCV dual infections and risk for oral cavity cancer. CONCLUSION: Our data suggest that HCV but not HBV infection is a risk factor for oral cavity cancer. In addition, subjects with HCV infection tend to be at early onset risk for oral cavity cancer. This finding needs to be replicated in further studies.

BACKGROUND: The aim of this study was to evaluate a possible association between malignancy and anxiety disorders (AD) in Taiwan. METHODS: We employed data from the National Health Insurance system of Taiwan. The AD cohort contained 24,066 patients with each patient randomly frequency matched according to age and sex with 4 individuals from the general population without AD. Cox's proportional hazard regression analysis was conducted to estimate the influence of AD on the risk of cancer. RESULTS: Among patients with AD, the overall risk of developing cancer was only 1% higher than among subjects without AD, and the difference was not significant (hazard ratio [HR] = 1.01, 95% confidence interval [95% CI] = 0.95-1.07). With regard to individual types of cancer, the risk of developing prostate cancer among male patients with AD was significantly higher (HR = 1.32, 95% CI = 1.02-1.71). On the other hand, the risk of cervical cancer among female patients with AD was marginally significantly lower than among female subjects without AD (HR = 0.72, 95% CI = 0.51-1.03). LIMITATIONS: One major limitation is the lack of information regarding the life style or behavior of patients in the NHI database, such as smoking and alcohol consumption. CONCLUSIONS: Despite the failure to identify a relationship between AD and the overall risk of cancer, we found that Taiwanese patients with AD had a higher risk of developing prostate cancer and a lower risk of developing cervical cancer.