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Aspirin (ASA) exerts an anti-tumor effect via the COX pathway. Clinical studies on the chemopreventive effects of ASA on uterine cancer (UC) remain inconsistent. We used population-based retrospective cohort study to evaluate the UC in ASA users in Taiwanese women. From insurance claims data, we identified 23,342 women received ASA treatment between 2000 and 2010 and a comparison group of same sample size randomly selected from the same database matched by the propensity score. The incidence of UC in the ASA cohort was 10% of that in the comparison group (0.28 vs 2.73 per 10,000 person-years). The Poisson regression analysis estimated adjusted incidence rate ratio (IRR) was 0.10 (95% confidence interval (CI) = 0.09–0.11) for ASA users relatives to comparisons after controlling for covariates. The UC incidence in ASA users decreased with age, from 0.61 per 10,000 person-years in the 20 to 39 years old (adjusted IRR = 0.21, 95% CI = 0.15–0.29) to 0.21 per 10,000 person-years in the 65 to 80 years old (adjusted IRR = 0.15, 95% CI = 0.12–0.16). The incidence was higher in longer term users. Hormone therapy of estradiol was associated with the increase of UC risk in both cohorts, but less in ASA users than comparisons (1.34 vs 4.75 per 10,000 person-years). This study suggests that ASA use was associated with a decreased risk of UC. Further prospective randomized clinical trials are warranted to confirm the association.

Studies on the relationship between gynecologic surgery and subsequent ovarian cancer have been carried out in limited Western ethnic groups. We aim to evaluate whether receiving hysterectomy and/or salpingectomy associated with ovarian cancer risk in Taiwan. From the Taiwan National Health Insurance Research Database, we identified a gynecologic surgery cohort consisting of women who had newly received hysterectomy (N = 181,151), salpingectomy (N = 45,410) or both hysterectomy and salpingectomy (N = 11,875) in 2000 to 2013. A comparison cohort of 953,744 women was randomly selected from women without the surgeries, frequency-matched by age and index date of the surgery case. They were followed up to identify subsequent ovarian cancer by the end of 2013. The overall ovarian cancer incidence was 4.4-fold greater in the gynecologic surgery cohort than in the comparison cohort (41.5 vs 9.43 per 106 person-years) with an adjusted hazard ratio of 3.86 (95% confidence interval = 2.56–5.84). Women with both hysterectomy and salpingectomy had the highest incidence and followed by women with hysterectomy or salpingectomy (52.5, 45.5, or 23.3 per 106 person-years, respectively). No ovarian cancer was noted in the subgroup with bilateral salpingectomies. We conclude that women with gynecologic surgery of hysterectomy and/or salpingectomy are at an increased risk of developing ovarian cancer, particularly among women who have had other gynecologic comorbidity. Women with gynecologic surgery and comorbidity deserve greater attention to prevent and screen for ovarian cancer.

In this study, we aimed to investigate the effect of hypoglycemia on cardiovascular outcomes in a sample of patients with chronic kidney disease (CKD).Information about study participants was extracted from the National Health Insurance Research Database of Taiwan for the years 1998 through 2008. We conducted this retrospective cohort study of patients with CKD, with and without hypoglycemia, to evaluate the risk of overall mortality and cardiovascular complications including stroke, coronary heart disease, and congestive heart failure in both groups.This study included 46,135 patients with CKD, of whom 2,117 (4.59%) were hospitalized and had hypoglycemia. Results of multivariate Cox proportional hazard regression analyses indicated that stroke (hazard ratio [HR] = 1.62, 95% confidence interval [CI] = 1.29-2.03), coronary heart disease (HR = 1.25, 95% CI = 1.00-1.57), congestive heart failure (HR = 1.49, 95% CI = 1.13-1.98), and death (HR = 2.53, 95% CI = 1.99-3.21) were associated with hypoglycemia in patients with CKD. Recurrent episodes of hypoglycemia were associated with a higher risk of death (HR = 33.0, 95% CI = 22.3-48.8 for2 episodes, p for trend0.0001), and a similar trend was observed for other multiple cardiovascular events. We observed an increased risk of stroke and overall mortality in patients with hypoglycemia compared to those without hypoglycemia, regardless of whether the patient had diabetes.CKD was associated with a higher risk of stroke and mortality in patients with hypoglycemia. Recurrent hypoglycemia considerably increased the risk of stroke and overall mortality in patients with CKD regardless of whether they had diabetes. These results suggest that hypoglycemia has a crucial role in stroke and death in patients with CKD.

Introduction:The aim of this systematic review is to investigate the effects of perioperative intravenous administration of MgSO4 on postoperative pain, analgesic consumption and adverse effects in patients undergoing orthopedic surgery.Methods:Two investigators independently searched for ar

Studies comparing mortality for Asian populations with end-stage renal disease (ESRD) on hemodialysis (HD) and peritoneal dialysis (PD) are limited. We compared mortality between patients treated with PD and HD in Taiwan, the population with the highest incidence of ESRD worldwide. Using the population-based insurance claims data of Taiwan from 1997 to 2006, we identified 4721 patients treated with PD and randomly selected 4721 patients treated with HD who were frequency-matched to the PD patients based on their propensity scores. In follow-up analyses we measured mortalities and hazard ratios associated with comorbidities in 2 different 5-year cohorts (1997-2001 and 2002-2006).In the 10-year period from 1997 to 2006, the overall mortality rates were similar in patients treated with PD and in patients treated with HD (12.0 vs. 11.7 per 100 person-years, respectively), with a PD-to-HD hazard ratio of 1.02 (95% confidence interval [CI], 0.96-1.08). In the first 5-year period (1997-2001), the hazard ratio for mortality was higher for PD (1.33; 95% CI, 1.21-1.46), but there was no difference between PD and HD in the 2002-2006 cohort. Of note, younger patients who received PD had better survival than younger patients who received HD; this was especially true for patients aged younger than 40 years.In summary, in this Asian population, no significant survival differences were noted between propensity score-matched PD and HD patients. The selection of a dialysis modality must be tailored to the individual patient. Studies in which patients who are appropriate for either modality are randomly assigned to HD or PD may provide helpful information to clinicians and patients.

Using population-based representative insurance claims data, the risk of developing hepatocellular carcinoma (HCC) among diabetes mellitus (DM) patients, as well as whether DM medications alter the risk of developing HCC were investigated.From the Taiwan National Health Insurance Research Database, 19,349 newly diagnosed DM patients 20 years and older and 77,396 comparison subjects without DM were identified from claims from 2000 to 2005. The incidences of HCC at the end of 2008 and the risks associated with hepatitis B and hepatitis C were determined. Whether metformin and thiazolidinediones reduce the risk of developing HCC was also measured.The incidence of HCC was twice higher in the DM group compared with the non-DM group (21.0 vs. 10.4 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.73 (95% confidence interval (CI)=1.47-2.03) using multivariable Cox proportional hazard regression. Male sex, cirrhosis, hepatitis B, and hepatitis C were significant independent factors that predict HCC, with HRs of 2.32, 8.65, 2.52, and 5.61, respectively. In the stratified analysis, the HR increased to 72.4 (95% CI=42.9-122) among patients with DM, cirrhosis, and hepatitis C. HCC risk reduction was greater for diabetics taking metformin than those taking thiazolidinediones (51 vs. 44% reduction).Comorbidity with cirrhosis and/or hepatitis appears to be associated with an extremely increased risk of developing HCC among DM patients. These high-risk patients should be closely monitored for HCC. The use of metformin or thiazolidinediones may reduce the risk of developing HCC.

Background and Purpose— Stroke is a known cerebrovascular complication in lung cancer patients; however, whether lung cancer patients are at elevated risk of developing stroke relative to the noncancer population remains unclear. Methods— The present study used population-based claims data from the Taiwan National Health Insurance, which identified 52 089 patients with an initial diagnosis of lung cancer between 1999 and 2007, and 104 178 matched noncancer subjects from all insured subjects age 20 years and older. Subsequent occurrence of stroke was measured until 2008, and the association between lung cancer and the hazard of developing stroke was estimated using Cox proportional hazard models. Results— The incidence of stroke was 1.5 times higher (25.9 versus 17.4 per 1000 person–years) in the lung cancer group compared with the comparison group. The multivariate-adjusted hazard ratio (HR) comparing lung cancer patients with the noncancer group was 1.47 (95% CI, 1.39–1.56) for stroke, 1.78 (95% CI, 1.54–2.05) for hemorrhagic stroke, and 1.43 (95% CI, 1.34–1.51) for ischemic stroke. The risk of stroke fell over time, decreasing after 1 year of follow-up for men and after 2 years of follow-up for women. Within the first year of follow-up, the risk of stroke peaked during the first 3 months for men and within 4 to 6 months for women. Conclusions— Lung cancer is associated with increased risk of subsequent stroke within 1 year after diagnosis for men and 2 years after diagnosis for women.

The objective of this study was to assess the risk of acute pancreatitis among patients with type 2 diabetes mellitus (DM) and identify the roles of co-morbidities and anti-diabetic drugs.From claims data of one million enrollees randomly sampled from a population covered by the Taiwan National Health Insurance, 19,518 adults with type 2 DM diagnosed between 2000 and 2005 were identified. In addition, 78,072 DM-free persons, frequency matched with sex, age, and index year for comparison were identified. Subjects were followed up until the end of 2008 or censored to ascertain incident acute pancreatitis cases and associations with co-morbidities and anti-diabetic drugs.Patients with type 2 DM had 1.95-fold greater incidence of acute pancreatitis compared with non-diabetics (27.7 vs. 14.2 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.89 (95% confidence interval (CI)=1.65-2.18) based on multivariable Cox regression analysis. Additive Poisson regression analysis revealed an absolute risk increase of 14.4 per 10,000 person-years (95% CI=13.4-15.5) among type 2 DM patients. Co-morbid alcoholism, hepatitis C infection, and gallstones yielded additional risk of acute pancreatitis among type 2 DM patients (absolute risk increase ranges 86.3, 41.1, and 23.5 per 10,000 person-years, respectively). Patients taking anti-diabetic drugs had a reduced risk of acute pancreatitis, however. The adjusted HR decreased to 0.31 (95% CI=0.18-0.56) among patients who took five different anti-diabetic drugs.Patients with type 2 DM are at an elevated risk of acute pancreatitis. Alcoholism, hepatitis C infection, and gallstones increase the risk further. However, anti-diabetic drugs reduce the risk as the number of drugs used increases and as the duration of treatment increases.

Background Few studies have investigated the viral isolation characteristics for severe complicated enterovirus infection (SCEI). This study evaluated the seasonality and contribution of circulated viruses to the chronologic trend and weekly reported SCEI epidemic. Methods Enterovirus infection surveillance and virology laboratory data in 2000 to 2008 obtained from the Centers for Disease Control in Taiwan were analyzed. We measured the monthly and weekly virology isolation rates by viral types. The virus-specific and the season-specific relative risks for SCEI and 95% confidence intervals (CI) associated with the isolated circulating viruses and weather status was evaluated. Results Among 1539 virology confirmed SCEI cases, the mean annual incidence rates ranged from 0.72/100,000 to 32.5/100,000 in children aged 5 years and less; rates were higher in warm months with cases peaking in June (12.6%). The untypeable nonpolio enterovirus was the most frequently isolated type among the monitored specimens (6.07%), followed by coxsackievirus A (3.99%), EV71 (1.77%), coxsackievirus B (1.56%), and echovirus (1.23%). However, these SCEI cases had very strong associations with the isolation of EV71 and coxsackievirus A and B. The corresponding relative risks were 1.14 (95% CI, 1.11-1.17), 1.03 (95% CI, 1.01-1.04), and 1.09 (95% CI, 1.07-1.12), respectively, for 1% increase in weekly isolation rate. Conclusions Isolation rates for EV71 and coxsackieviruses A and B can predict the development of SCEI cases, particularly in warm months.

No study has investigated the role of pancreatic cancer in the stroke risk using population data. We used claims data obtained from a universal health insurance program of Taiwan to evaluate the stroke risk in pancreatic cancer patients.From the catastrophic disease registry of the insurance, we identified 7479 patients with pancreatic malignancy without stroke history from 2000 to 2009. The comparison cohort consisted of 29,916 individuals identified from 1 million insured people without cancer and stroke history, matching with the cancer cohort by propensity score. We followed each selected individual until stroke was diagnosed or until being censored for death or withdrawal from insurance, or for a maximum of 3 follow-up years, or the end of 2011.The pancreatic cancer cohort had a 2.3-fold greater incident stroke than comparisons had (28.5 vs 12.3 per 1000 person-years), with an adjusted hazard ratio (aHR) of 2.74 (95% confidence interval (CI) = 2.31-3.24) after controlling for covariates, or a subdistribution hazard ratio (SHR) of 2.04 (95% CI = 1.74-2.40) accounting for the competing risk of deaths. During the follow-up period, stroke events occurred constantly in comparisons, but declined rapidly in the cancer cohort. The pancreatic cancer cohort had a stroke incidence of 46.6 per 1000 person-years within 6 months postdiagnosis, with an aHR of 4.37 (95% CI = 3.45-5.54) and a SHR of 3.87 (95% CI = 3.08-4.86), relative to comparisons.Our study suggests that patients with pancreatic cancer are at an elevated risk of stroke, patients deserve sufficient follow-up care, particularly in the first 6 months after the diagnosis of the cancer, and for those with comorbidities.

Objective To examine the relationship between short-term changes in BMI and the development of hypertension in a cohort of ethnic Chinese men and women. Methods BMI changes between the baseline survey in 1990-1991 and examinations in 1992-1993 were evaluated for 713 men and 853 women aged 35 years or above, free from hypertension, stroke, coronary heart disease and diabetes at the baseline. The incident hypertension and associated risks were assessed in follow-up visits in 2000. Results Both men and women in the highest BMI change quartile had the highest adjusted mean blood pressures at the initial follow-up period. The differences in blood pressure between the extreme quartiles of BMI changes remained significant at the end of follow-up period in men but were notably reduced in women. The risk of incident hypertension increased as the BMI change quartile increased in men (multivariate-adjusted hazard ratio and 95% confidence interval for the highest quartile versus the lowest quartile: 1.81, 1.22-2.68, respectively, P for trend = 0.002). However, in women, the BMI gain effect on hypertension was not significant unless menopausal status was included in the adjustment (hazard ratio and 95% confidence interval: 1.46, 1.04-2.06, respectively). Stratified analyses showed that the BMI change effect was significant only in women in the premenopause or transition to menopause during their BMI change period. Conclusion The 2-year substantial BMI gain is associated with a persistent risk for developing hypertension in men. The risk for women is influenced by their menopause status.

PURPOSE: Polymorphic cytochrome P-450 1A2, N-acetyltransferase 1, and 2 are important enzymes involved in the biotransformation of aromatic and heterocyclic amines known as carcinogens for colorectal cancer. A hospital-based study was designed to investigate the association between colorectal cancer and cytochrome P-450 1A2, N-acetyltransferase 1, and N-acetyltransferase 2, with the interaction of meat consumption. METHODS: We genotyped these polymorphisms for 727 colorectal cancer cases and 736 healthy controls. Information on sociodemographic characteristics and diet were ascertained using a structured questionnaire. RESULTS: The colorectal cancer risk was significantly increased in rapid N-acetyltransferase 1 carriers with high white meat consumption (almost every day) compared to those carrying the slow N-acetyltransferase 1 genotype with low white meat consumption (less than once a week, odds ratio, 3.00; 95 percent confidence interval, 1.83-4.92). Furthermore, a gene-gene interaction between cytochrome P-450 1A2*1C and N-acetyltransferase 1 was found and modulated by white meat consumption. CONCLUSIONS: N-acetyltransferase 1 might compete with cytochrome P-450 1A2*1C to increase the colorectal cancer risk in intermediate white meat consumers, whereas the rapid N-acetyltransferase 1 genotype may exert a harmful effect on individuals with high carcinogen exposure.

Hypertension confers risk on cardiovascular events; however, less is known concerning hypertension incidence among ethnic Chinese. The effect of prehypertension on new onset of hypertension and cardiovascular events is also unknown.To investigate the incidence of hypertension, risk factors and cardiovascular events in Taiwan.A prospective community-based cohort design.The Chin-Shan Community Cardiovascular Cohort consisted of 1703 men and 1899 women aged 35 years old and above, of homogeneous Chinese ethnicity, from 1990 to 2005.Hypertension incidence rates, cardiovascular events.The patterns of adjusted cumulative incidence probability were curvilinear, increasing from 1% in the first period to 27% in the fourth period in normotensive subjects. The patterns among pre-hypertensives were from 4% in the first period to 59% in the fourth period. Women had an 18% lower risk of developing hypertension than men. The survival curves were distinctly different for different blood pressure categories (P0.001). Baseline blood pressure categories played important roles in predicting cardiovascular risks; the hazard risks of prehypertension and hypertension increased from 1.73 to 4.52, compared with baseline normotensive subjects.The hypertension incidence rates among ethnic adult Chinese were high and were associated with obesity and metabolic syndrome status. Furthermore, the baseline prehypertension elicited significant risk of cardiovascular events in the community.

Objective: This study investigated electrocardiography (ECG) manifestations for male workers with carbon disulfide exposure at rayon manufacturing plants. Methods: A total of 251 men in the exposure group and 226 administrative clerks in the reference group received physical examinations and completed questionnaires. Results: The prevalence of ECG abnormalities was much higher in the carbon disulfide exposure group (25.9%, n = 65) than in the reference group (2.7%, n = 6), with an odds ratio (OR) of 12.8 (95% confidence interval [CI] = 5. 4 -30. 2). The foremen were at the highest risk of abnormal ECG (OR = 20.6, 95% CI = 6.5-65.2), followed by filament-spinning workers (OR = 14.2, 95% CI = 5.7-35.3), viscose-manufacturing workers (OR = 11.3, 95% CI = 4.3-30.1), and carbon disulfide-manufacturing workers (OR = 8.1, 95% CI = 2.7-25.6). The multivariate logistic regression analysis based on cumulative exposure index also showed a dose-response relationship with the exposure, and the risk of ECG abnormality could be initiated at the exposure history of 31 to 57 year-ppm with an OR of 7.2 (95 % CI = 1.5-36.7). Conclusions: In general, the ECG abnormalities observed in workers at the permissible exposure level of carbon disulfide implicate the importance of environmental control of the chemical and of workers' education in exposure prevention at work.

Background and Purpose — There are limited prospective cohort studies of the well-known association between stroke events and serum lipids for the Taiwanese population, in whom stroke is the second most common cause of death. Methods — This report describes the effect of dyslipidemia on the risk of stroke in a community-based cohort consisting of 3602 adults aged ≥35 years, established in 1990 in the Chin-Shan community in Taipei County, Taiwan. Results — As of the end of 1998, 97 stroke incidence cases were identified from medical records and death certificates (53 in men and 44 in women). The female-to-male stroke event rates increased from 0.42 in the youngest group (aged 35 to 44 years) to 1.38 in the oldest (aged ≥75 years). Multiple Cox proportional hazard regression models controlling for age and sex revealed that individuals with serum apolipoprotein A-I (apoA-I) at the highest quartile were more likely to have a stroke event than those at the lowest quartile level (relative risk [RR]=2.02, P for trend=0.010). The corresponding risk of stroke predicted by apolipoprotein B (apoB) was also significant (RR=1.88, P for trend=0.020). After adjustment for age, sex, hypertension, and diabetes status, the interaction between hypertension and apoA-I level remained significant in predicting stroke events in men but not in women (RR=1.71, P =0.033 in men; RR=2.29, P =0.071 in women). Conclusions — We conclude that apoA-I but not apoB levels may serve as an effect modifier of hypertension for the risk of stroke events.

Occupational exposure to power-frequency electromagnetic fields (PF-EMF) has been suspected of being associated with adverse neurological outcomes. We performed a case-control study to assess the relationship between exposure to PF-EMF and the risk of cognitive impairment, an indication of certain adverse neurological diseases such as Alzheimer's disease and dementia. Among 2198 elderly individuals aged 65 years or older, 290 persons with score-based cognitive impairment were compared with 580 sex-matched controls to assess the risk of cognitive impairment in relation to PF-EMF exposure. Participants who were former electrical workers or living within 100 meters of high-voltage transmission lines were considered to have higher exposure. Compared with background exposure, the risk was equal or close to unity for participants with higher exposure from a previous occupation (odds ratio [OR], 1.3; 95% confidence interval [CI], 0.7 to 2.3), higher residential exposure (OR, 0.9; 95% CI, 0.3 to 2.6), or higher exposure in both occupation and residential environments (OR, 1.0; 95% CI, 0.2 to 4.6). Our findings provide little support for the link between PF-EMF and cognitive impairment. Nevertheless, the study results do not preclude the possible association between PF-EMF and any specific neurodegenerative disease previously investigated.

Dermatologic diseases are not traditional risk factors of stroke, but recent studies show atopic dermatitis, psoriasis, and bullous skin disease may increase the risk of stroke and other cardiovascular diseases. No previous studies have focused on the association between contact dermatitis and stroke.We established a cohort comprised of 48,169 contact dermatitis patients newly diagnosed in 2000-2003 and 96,338 randomly selected subjects without the disorder, frequency matched by sex, age, and diagnosis year, as the comparison cohort. None of them had a history of stroke. Stroke incidence was assessed by the end of 2011 for both cohorts.The incidence stroke was 1.1-fold higher in the contact dermatitis cohort than in the comparison cohort (5.93 vs 5.37 per 1000 person-years, P < 0.01). The multivariable Cox method analyzed adjusted hazard ratios (aHRs) were 1.12 (95% confidence interval [CI], 1.05-1.19) for all stroke types and 1.12 (95% CI, 1.05-1.20) for ischemic stroke and 1.11 (95% CI, 0.94-1.30) for hemorrhagic stroke. The age-specific aHR of stroke for contact dermatitis cohort increased with age, from 1.14 (95% CI, 1.03-1.27) for 65 to 74 years; to 1.27 (95% CI, 1.15-1.42) for 75 years and older. The aHR of stroke were 1.16 (95% CI, 1.07-1.27) and 1.09 (95% CI, 1.00-1.18) for men and women, respectively.This study suggests that patients with contact dermatitis were at a modestly increased risk of stroke, significant for ischemic stroke but not for hemorrhagic stroke. Comorbidity, particularly hypertension, increased the hazard of stroke further.

Vagus nerve may play a role in serum glucose modulation. The complicated peptic ulcer patients (with perforation or/and bleeding) who received surgical procedures with or without vagotomy provided 2 patient populations for studying the impact of vagus nerve integrity. We assessed the risk of developing type 2 diabetes in peptic ulcer patients without and with complications by surgical treatment received in a retrospective population study using the National Health Insurance database in Taiwan.A cohort of 163,385 patients with peptic ulcer and without Helicobacter pylori infection in 2000 to 2003 was established. A randomly selected cohort of 163,385 persons without peptic ulcer matched by age, sex, hypertension, hyperlipidemia, Charlson comorbidity index score, and index year was utilized for comparison. The risks of developing diabetes in both cohorts and in the complicated peptic ulcer patients who received truncal vagotomy or simple suture/hemostasis (SSH) were assessed at the end of 2011.The overall diabetes incidence was higher in patients with peptic ulcer than those without peptic ulcer (15.87 vs 12.60 per 1000 person-years) by an adjusted hazard ratio (aHR) of 1.43 (95% confidence interval [CI] = 1.40-1.47) based on the multivariable Cox proportional hazards regression analysis (competing risk). Comparing ulcer patients with truncal vagotomy and SSH or those without surgical treatment, the aHR was the lowest in the vagotomy group (0.48, 95% CI = 0.41-0.56).Peptic ulcer patients have an elevated risk of developing type 2 diabetes. Moreover, there were associations of vagus nerve severance and decreased risk of subsequent type 2 diabetes in complicated peptic ulcer patients.

Supplemental Digital Content is available in the text, The use of validated patient-reported outcome (PRO) instruments for the treatment outcome measure of laryngopharyngeal reflux (LPR) is crucial given the lack of objective markers. However, current symptom-based PRO instruments can only partially capture the impact of LPR. The GERD Analyzer (GERDyzer), an existing disease-specific PRO instrument, which measures multidimensional health-related quality of life (HRQL) affected by the illness rather than by any specific symptoms, has been validated in patients with erosive gastroesophageal reflux disease (GERD). Following the U.S. Food and Drug Administration PRO guidance, we cross-culturally adapted the GERDyzer instrument into Chinese, and examined the qualitative and quantitative psychometric properties of the Chinese version GERDyzer in pH-test-proven LPR patients. The GERDyzer comprises 10 dimensions of HRQL, including general well-being, pain/discomfort, physical health, diet, energy, activities, leisure activities, social life, mood, and sleep. To examine the content validity, we recruited 26 pH-test-proven LPR participants to conduct 4 focus group meetings for direct patient input on clinical manifestations and HRQL impacts. We also tested the quantitative psychometric properties, including reliability, validity, and responsiveness in 100 pH-test-proven LPR patients. Saturation of concept elicitation was achieved from the 4 focus groups, and a strong conceptual match was evident between the GERDyzer contents and responses from the focus group participants. Cognitive debriefing assessment showed that the Chinese version GERDyzer was adequate for use by patients as it demonstrated linguistic validation and cultural harmonization. Quantitative psychometric properties showed evidence of high internal consistency (Cronbach α: 0.96), good to excellent test-retest reliability (intraclass correlation coefficient: 0.84–0.98). Confirmatory factor analysis supported a 2-factor structure. Convergent validity was confirmed by moderate correlation assessments referencing the Reflux Symptoms Index and the Reflux Questionnaire. The discriminant validity was supported by the ability to discriminate moderate-to-severe disease from mild disease. The responsiveness was also high in participants with and without typical GERD symptoms (effect sizes 1.20 and 1.21, respectively). In conclusion, the Chinese version GERDyzer instrument is a reliable, valid, and responsive instrument for assessing HRQL in Taiwanese patients with LPR.

Treatment of periodontal diseases has been associated with benefit outcomes for patients with chronic obstructive pulmonary disease (COPD). However, no population-based cohort study has been conducted. We evaluated this relationship by retrospective cohort study using a large population data. Using the National Health Insurance claims data of Taiwan, we identified 5562 COPD patients with periodontal diseases who had received periodontal treatment as the treatment group. The comparison group was selected at a 1:1 ratio matched by the propensity score estimated with age, sex, date of COPD diagnosis and periodontal treatment, and comorbidities. Both groups were followed up for 5 years to compare risks of acute exacerbation, pneumonia, and acute respiratory failure. The incidence rates of adverse respiratory events were significantly lower in the treatment group than in the comparison group: 3.79 versus 4.21 per 100 person-years for emergency room visits, 2.75 versus 3.65 per 100 person-years for hospitalizations, and 0.66 versus 0.75 per 100 person-years for intensive care unit admissions. The treatment group also had a 37% reduced risk of deaths (1.81 vs 2.87 per 100 person-years), with an adjusted hazard ratio of 0.57 (95% confidence interval 0.52–0.62). Periodontal treatment for COPD patients could reduce the risk of adverse respiratory events and mortality. The adequate periodontal health care is important for COPD patients with periodontal diseases.

No large-scale population-based cohort study has ever investigated the risk of developing chronic obstructive pulmonary disease (COPD) in patients with Sjogren syndrome (SS). This study evaluated the risk of COPD in women with primary SS (pSS) in a nationwide population. We used the data of the National Health Insurance Research Database of Taiwan to establish a pSS group consisting of 3013 female adults diagnosed between 2000 and 2005, and a non-SS group consisting of 12,052 women without SS matched by a propensity score. Incident COPD cases were identified to the end of 2011. The pSS group to non-SS group adjusted hazard ratios (aHRs) of COPD were estimated using multivariable Cox proportional hazards regression analysis. After a mean follow-up period of 7.99 years, the incidence of COPD was 1.4-fold greater in the pSS group than in the non-SS group (3.87 vs 2.77 per 1000 person-years) with an aHR of 1.39 (95% confidence interval [CI] = 1.10–1.75, P = 0.007). The COPD incidence was 7-fold greater for women aged 50 years and above than women aged 20 to 49, with the aHR of 4.24 (95% CI = 3.06–5.88, P

The present study evaluated the dementia risk after carbon monoxide poisoning (CO poisoning). Using the National Health Insurance Research Database of Taiwan, a total of 9041 adults newly diagnosed with CO poisoning from 2000 to 2011 were identified as the CO poisoning cohort. Four-fold (N = 36,160) of non-CO poisoning insured people were randomly selected as controls, frequency-matched by age, sex, and hospitalization year. Incidence and hazard ratio (HR) of dementia were measured by the end 2011. The dementia incidence was 1.6-fold higher in the CO exposed cohort than in the non-exposed cohort (15.2 vs 9.76 per 10,000 person-years; n = 62 vs 174) with an adjusted HR of 1.50 (95% CI = 1.11-2.04). The sex- and age-specific hazards were higher in male patients (adjusted HR = 1.74, 95% CI = 1.20-2.54), and those aged

Asthma has been associated with the atherosclerosis risk, but not clear of peripheral artery disease (PAD). We attempted to examine the risk of PAD in patients with asthma. From the insurance claims data of Taiwan, we identified 28,158 newly diagnosed asthma patients in 2000 to 2005 and 56,316 persons without asthma randomly selected into the comparison cohort, frequency matched by sex, age, and the date of diagnosis. Both cohorts were followed up until the end of 2011 to estimate the incident PAD. Adjusted hazard ratios (aHRs) of PAD were estimated using the Cox proportional hazards model after controlling for sex, age, and comorbidities. The incidence of PAD was 1.46 times higher in the asthma cohort than in the comparison cohort, with an aHR of 1.34 [95% confidence interval (CI) = 1.24–1.45]. Incidence of PAD was higher in men, the aged, and those with comorbidities in both cohorts. The aHRs of PAD remained significant for the asthma cohort in all subgroups of sex, age, and the presence of comorbidity. The aHRs of PAD were 14.1 (95% CI = 8.18–24.5) in asthma patients with multiple emergency visits and 22.3 (95% CI = 15.6–31.9) for those with multiple hospitalizations. Although smoking is a potential confounding factor, this study suggests patients with asthma have a significantly higher risk of developing PAD than the general population. The results also support the notion that poor control of asthma status is a key factor in subsequent PAD development.

Several studies have reported an association between chronic obstructive pulmonary disease (COPD) and periodontal diseases. However, a large-scale population-based cohort study was previously absent from the literature. Therefore, we evaluated the risk of periodontal diseases in patients with COPD in a nationwide population.From the National Health Insurance claims data of Taiwan, we identified 22,332 patients with COPD who were newly diagnosed during 2000 to 2010. For each case, two individuals without COPD were randomly selected and frequency matched by age, sex, and diagnosis year. Both groups were followed up till the end of 2011.The overall incidence of periodontal diseases was 1.19-fold greater in the COPD group than in the comparison group (32.2 vs 26.4 per 1000 person-years; 95% confidence interval [CI] 1.15-1.24). Compared with non-COPD patients, the adjusted hazard ratios of patients with COPD increased with the number of emergency room visits (from 1.14 [95% CI 1.10-1.19] to 5.09 [95% CI 4.53-5.72]) and admissions (from 1.15 [95% CI 1.10-1.20] to 3.17 [95% CI 2.81-3.57]). In addition, the adjusted hazard ratios of patients with COPD treated with inhaled corticosteroids (1.22, 95% CI 1.11-1.34) and systemic corticosteroids (1.15, 95% CI 1.07-1.23) were significantly higher than those of patients not treated with corticosteroids.Patient with COPD are at a higher risk of developing periodontal diseases than the general population. Our results also support that the risk of periodontal diseases is proportional to COPD control. In addition, patients who receive corticosteroid treatment are at a higher risk of developing periodontal diseases.

The aim of the study was to investigate the association between statin use and open-angle glaucoma (OAG) risk in hyperlipidemia patients. We used the research database of the Taiwan National Health Insurance program to conduct a population-based case-control study. A total of 1276 patients with newly diagnosed OAG were identified from 2004 to 2011. Controls comprised of 12,760 patients without glaucoma and were frequency-matched for age, sex, history of diabetes mellitus, and year of hyperlipidemia diagnosis at a 1:10 ratio. Accumulated defined daily doses (DDDs) of statins prescribed during follow-up were calculated. Average statin use was calculated as the sum of DDDs divided by the duration from the initial statin prescription date to the index date (per year), and was subdivided into 3 levels

The purpose of this study was to examine the association of glucose variability using coefficient of variation of fasting plasma glucose (FPG-CV) and coefficient of variation of glycated hemoglobin (HbA1c-CV) to end-stage renal disease (ESRD) in 31,841 Chinese patients with type 2 diabetes. Patients with type 2 diabetes enrolled in National Diabetes Care Management Program, aged ≧30 years, and free of ESRD (n = 31,841) in January 1, 2002 to December 31, 2004 were included. Extended Cox proportional hazards regression models with competing risk of all-cause mortality were used to evaluate risk factors on ESRD incidence. Patients were followed till 2012. After a median follow-up period of 8.23 years, 1642 patients developed ESRD, giving a crude incidence rate of 6.27/1000 person-years (6.36 for men, 6.19 for women). After the multivariate adjustment, both FPG-CV and HbA1c-CV were independent predictors of ESRD with corresponding hazard ratios of 1.20 (95% confidence interval [CI] 1.01, 1.41), 1.24 (95% CI 1.05, 1.46) in HbA1c-CV from fourth to fifth quintile and 1.23 (95% CI 1.03, 1.47) in FPG-CV from fifth quintile. One-year visit-to-visit glucose variability expressed by FPG-CV and HbA1c-CV predicted development of ESRD in patients with type 2 diabetes, suggesting therapeutic strategies toward a goal to minimize glucose fluctuation.

The aim of this study was to elucidate the relationship between spinal cord injury (SCI) and the risk of peripheral arterial disease (PAD) in a cohort study with a large representative sample. The National Health Insurance Database was used to select patients who were diagnosed from 2000 to 2010. Patients with a history of PAD were excluded. The SCI group comprised 42,673 patients diagnosed with SCI, and we enrolled 170,389 matched controls (non-SCI group). We used a Cox proportional hazards regression model to analyze the adjusted risk of PAD between the case and control patients. Patients with SCI exhibited a significantly higher risk (hazard ratio [HR] = 1.37; 95% confidence interval [CI] = 1.22–1.53) of PAD than patients without SCI. Patients with diabetes were at the highest risk of developing PAD (adjusted HR = 3.11, 95% CI = 2.80–3.44). Among patients without comorbidity, SCI patients exhibited a significantly higher risk of PAD than non-SCI patients. Furthermore, lumbar, sacral, or coccygeal spine, and multiple spine SCI were significantly associated with an increased risk of PAD (HR = 1.56, 95% CI = 1.33–1.84, HR = 2.11, 95% CI = 1.59–2.79, respectively). SCI is associated with an increased risk of PAD. Future studies should focus on modifying risk factors to reduce PAD risk among patients with SCI.

Little was known about the effects of acupuncture on stroke recurrence. The aim of this study is to investigate whether ischemic stroke patients receiving acupuncture treatment have a decreased risk of stroke recurrence. A retrospective cohort study of 30,058 newly diagnosed cases of ischemic stroke in 2000 to 2004 was conducted based on the claims of Taiwan National Health Insurance Research Database. The use of acupuncture treatment and stroke recurrence were identified during the follow-up period from 2000 to 2009. This study compared the risk of stroke recurrence between ischemic stroke cohorts with and without acupuncture treatment by calculating adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of acupuncture associated with stroke recurrence in the Cox proportional hazard model. The stroke recurrence rate per 1000 person-years decreased from 71.4 without to 69.9 with acupuncture treatment (P

End-stage renal disease (ESRD) is a well-known risk factor for septicemia. Renal transplantation (RTx) is the treatment of choice for ESRD. However, RTx recipients should undergo long-term immunosuppressive therapy. The aim of this study was to evaluate the risk of septicemia in ESRD patients with and without RTx.This cohort study used the National Health Insurance (NHI) data of Taiwan from 2000 to 2010. The RTx group consisted of 3286 RTx recipients. The non-RTx comparison group also consisted of 3286 subjects with ESRD matched by propensity scores for age, sex, index date, comorbidities, and medications. The subjects were followed until the end of 2011 to evaluate the septicemia risk.The risk of septicemia was lower in the RTx group than the non-RTx group, with an adjusted hazard ratio of 0.73 [95% confidence interval (CI) = 0.64-0.84, P < 0.001]. In addition, we observed insignificantly lower intensive care unit (ICU) admission rate (35.8% vs. 39.8%) and lower 30-day all-cause mortality rate (17.2% vs. 18.5%) in the RTx group than the non-RTx group. However, the mean cost for septicemia in the RTx group was insignificantly higher than the non-RTx group (7175 vs. 6421 USD, P = 0.39).RTx recipients had a significantly reduced risk of developing septicemia compared to the propensity-matched non-RTx ESRD patients. The ICU admission and 30-day all-cause mortality rates also slightly decreased in RTx recipients but without statistical significance.

There are limited population-based studies on the progress of oseltamivir therapy for influenza infection. Using insurance claims data of 2005, 2009, and 2010, the authors established an “in-time” cohort and a “lag-time” cohort representing influenza patients taking the medicine within and not within 1 week to examine the treatment progress. Incident outpatient visit, emergency care and hospitalization, and fatality were compared between the 2 cohorts in the first week and the second week of follow-up periods, after the oseltamivir therapy. A total of 112,492 subjects diagnosed with influenza on oseltamivir therapy in 2005, 2009, and 2010 were identified. The multivariate logistic regression analysis showed that the in-time treatment was superior to the lag-time treatment with less repeat outpatient visits, hospitalizations, and fatality. The overall corresponding in-time treatment to lag-time treatment odds ratios (OR) were 0.50, 0.54, and 0.71 (all P value

Previous studies have shown that metformin or statins may decrease hepatocellular carcinoma (HCC) in diabetic patients. Accordingly, this article evaluates whether combination therapy may further reduce HCC. Newly diagnosed type 2 diabetes mellitus (DM) patients, excluding those with history of malignancy prior to the date of DM diagnosis, were recruited to a DM cohort. DM patients developed HCC as the cancer cohort and the date for HCC diagnosis as index date. Non-cancer cohort was frequency matched with 4:1 according to age, sex, DM-year, and index date as case group from DM cohort. Patients who were treated with statins showed a 63% decreased risk of HCC (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.27–0.49). Patients who consumed simvastatin, atorvastatin, or rosuvastatin significantly decreased risk for HCC (OR = 0.32, 0.31, and 0.22; 95% CI = 0.18–0.58, 0.19–0.52, and 0.08–0.61, respectively). Metformin combinations with simvastatin, atorvastatin, or rosuvastatin may decrease HCC (OR = 0.30, 0.30, and 0.24; 95% CI = 0.15–0.59, 0.16–0.54, and 0.08–0.70, respectively). The comorbidities for HCC were decreased by consuming simvastatin and atorvastatin (OR = 0.31 and 0.29; 95% CI = 0.14–0.67 and 0.15–0.57, respectively). Only combination therapy of metformin and simvastatin may significantly decreased HCC comorbidities (OR = 0.26; 95% CI = 0.11–0.60) in our study. In Asia, not all metformin combinations with statins may reduce the incidence of HCC and not all of this kind of combination therapy may decrease the HCC comorbidities.

The prevalence of erectile dysfunction (ED) in patients with chronic obstructive pulmonary disease (COPD) seemed high; however, large scale of population-based study was absent.We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan. The cohor

The association between cholelithiasis and depression remains unclear. We examined the risk of depression in patients with cholelithiasis. From the National Health Insurance population claims data of Taiwan, we identified 14071 newly diagnosed cholelithiasis patients (4969 symptomatic and 9102 asymptomatic) from 2000 to 2010. For each cholelithiasis patient, 4 persons without cholelithiasis were randomly selected in the control cohort from the general population frequency matched by age, sex, and diagnosis year. Both cohorts were followed up until the end of 2011 to monitor the occurrence of depression. Adjusted hazard ratios (aHRs) of depression were estimated using the Cox proportional hazards model after controlling for age, sex and comorbidities. The overall incidence rates of depression were 1.87- and 1.83-fold greater in the symptomatic and asymptomatic cholelithiasis subcohorts than in the control cohort (incidence, 10.1 and 9.96 vs 5.43 per 1000 person-years, respectively). The multivariable Cox proportional hazards regression analysis revealed higher variable-specific aHRs in women than in men, in younger patients than in older patients, and in those without comorbidities than in those with any comorbidity. Cholecystectomy reduced the hazard of developing depression with aHRs of 0.79 (95% confidence interval [CI] 0.62–0.99) for symptomatic cholelithiasis patients and 0.76 (95% CI 0.60–0.96) for asymptomatic patients. Patients with cholelithiasis are at a higher risk of developing depression than the general population. Patients could be benefited from cholecystectomy and have the hazard of developing depression significantly reduced.

Dementia is among various diseases affecting the elderly, who is also at a high risk for fractures. This study aimed to evaluate the association between fracture history and sequential risk of dementia in Taiwan. A retrospective cohort study was designed using the claims data of the entire insured residents covered by Taiwan's universal health insurance from 1998 to 2010. A total of 66,797 patients with fractures and 133,594 control subjects without fractures were matched in terms of age (±5 years), sex, and index year and then recruited. Fractures and dementia were defined in accordance with the International Classification of Diseases, 9th Revision, Clinical Modification. The influence of fractures on the risk of dementia was analyzed using a Cox proportional hazards model. After a 12-year follow-up period, 2775 and 3991 incident cases of dementia were reported in exposed and unexposed cohorts, respectively. The overall incidence rate of dementia in individuals with fractures was 41% higher than that in individuals without fractures (6.05 vs 4.30 per 1000 person-years) at an adjusted hazard ratio of 1.38 (95% confidence interval 1.32–1.45) after age, sex, urbanization, and individual disorders or comorbidities were adjusted. Considering fracture location, we found that patients with hip fractures were at a slightly high risk for dementia. The occurrence of multiple fractures at a single visit was also significantly associated with an increased risk of dementia. Fracture history is regarded as an independent risk factor of dementia in individuals aged ≥65 years, particularly those who suffered from multiple fractures and/or fractures located in the hip. Further studies are needed to support an independent role of fracture in dementia considering the clinical information and other comorbidities.