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OBJECTIVE Endometriosis and pelvic inflammatory disease are considered to be risk factors for ovarian cancer, as dysbiosis probably contributes to ovarian cancer development via chronic inflammation and immune response alteration. Therefore, we hypothesized that pelvic inflammatory disease predisposes to ovarian cancer development in women with endometriosis. METHODS We selected patients who were diagnosed with endometriosis or pelvic inflammatory disease between January 1, 2000 and December 31, 2015, in a 2 million longitudinal health and welfare database in Taiwan with cancer and death registries. Patients were divided into five groups: (1) those with endometriosis, (2) those with pelvic inflammatory disease, (3) those with endometriosis diagnosed before pelvic inflammatory disease, (4) those with pelvic inflammatory disease diagnosed before endometriosis, and (5) healthy women. Propensity score matching with inverse probability of treatment weighting was used to adjust for covariates across the study groups. RESULTS The risk of ovarian cancer was significantly higher in women with endometriosis and subsequent pelvic inflammatory disease than in those with endometriosis alone (hazard ratio 8.07; 95% confidence interval 4.53-14.37; P

This study investigated healthcare utilization and expenditure for patients with type 2 diabetes mellitus and schizophrenia and associated factors. Healthcare utilization (outpatient visits and hospitalization) and expenditure (outpatient, inpatient, and total medical expenditure) between 2002 and 2013 of patients with T2DM with schizophrenia (case group) and without (control group) were examined using the Taiwan National Health Insurance Research Database. (1) The average total numbers of outpatient visits and hospital admissions of the case group were 35.14 outpatient visits and 1.09 hospital admissions significantly higher than those of the control group in the whole study period (based on every 3-year period). Nonpsychiatric outpatient visits and nonpsychiatric hospital admissions were significantly more numerous for the case group. (2) The total outpatient expenditure, total inpatient expenditure, and total medical expenditure of the case group were NT$65,000, NT$170,000, and NT$235,000 significantly higher than those of the control group, respectively. Nonpsychiatric outpatient expenditure was significantly lower for the case group, but the inpatient and total nonpsychiatric medical expenditure were similar between groups. (3) Patients who were elder of low income, with complications, and high diabetes mellitus complication severity index had higher total numbers of outpatient visits and hospitalizations and medical expenditure. (4) Women had a higher number of outpatient visits but a lower number of hospitalization and medical expenditure. Lower non-psychiatric outpatient expenditure despite more visits indicated non-psychiatrist may not understand schizophrenia patients and cannot communicate well with them, leading to neglect of medical evaluation and treatment that should be carried out.

Objectives: To investigate the association between major depressive disorder (MDD) and the competing risk of Alzheimer's dementia (AD) and non-Alzheimer's dementia (NAD) using a nationwide population-based health insurance database.Methods: From Taiwan's National Health Insurance Research Database, we extracted claims data of 13,067 patients with MDD and 52,268 non-MDD controls matched by index date, age, sex, geographical area, monthly income, and selected comorbidities through propensity score matching. Follow-up durations in person-years were calculated for each person until dementia diagnosis, death, or the end of 2013. Competing incident risks of AD and NAD between patients with MDD and non-MDD.Results: In this study, 335 (2.6%) of the 13,067 MDD patients and 313 (0.6%) of the 52,268 non-MDDs developed AD. During the follow-up period, 73 (0.59%) of the 13,067 MDD patients developed NAD and 80 (0.15%) of the 52,268 non-MDD developed NAD. The patients with MDD had 4.73 and 3.69 times higher risks of AD (adjusted subdistribution hazard ratio [SHR] 4.73; 95% confidence interval [CI] 4.05-5.52) and NAD (adjusted SHR 3.69; 95% CI 2.68-5.08), respectively, than the controls.Conclusions: The patients with MDD had significantly higher incidence rates of AD and NAD than the controls, in particular among aged 65 and above. Additional studies are required to clarify the underlying pathophysiology between the MDD-dementia association and investigate whether prompt intervention in MDD can reduce the risk of dementia.

Purpose: To investigate the risk of recurrent corneal erosion (RCE) in patients with atopic keratoconjunctivitis (AKC).Methods: This national, retrospective, matched cohort study enrolled 184,166 newly-diagnosed AKC patients, selected from the Taiwan National Health Insurance Research Database and identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 372.05. The control group comprised 184,166 non-AKC patients matched by age, sex, and potential comorbidities and they were selected from the Taiwan Longitudinal Health Insurance Database, 2000. Information from patients was gathered from 1 January 2004 to 31 December 2011, and both groups were traced from the index date until December 2013. The incidence and risk of RCE (ICD-9-CM code 361.42) was compared between the groups. The adjusted hazard ratio (HR) for RCE was obtained by a Cox proportional hazard regression analysis. The Kaplan–Meier analysis was performed to calculate the cumulative incidence of RCE.Results: In total, 564 AKC patients and 406 non-AKC controls developed RCE during the follow-up span. The incidence of RCE was 1.45 times higher in AKC patients than in controls (95% confidence interval [CI] = 1.27–1.64; P < 0.0001). After adjusting for potential confounders, including diabetes mellitus, keratoconjunctivitis sicca, corneal transplantation, ocular blunt trauma, corneal dystrophy, and band keratopathy, AKC patients were 1.36 times more likely to develop RCE than controls (adjusted HR, 1.36; 95% CI = 1.19–1.54; p < 0.05).Conclusions: AKC Patients had an increased risk of developing RCE and should be informed of this risk.

Objectives Dentists may have a higher risk of developing lumbar herniated intervertebral disc (HIVD) due to prolonged sitting and improper postures during work. We conducted this study to delineate this issue, which is still unclear. Methods This nationwide population‐based study was conducted using Taiwan National Health Insurance Research Database. We identified 10 734 dentists, 72 066 non‐dentist health‐care providers (HCPs), and an identical number of age‐ and gender‐matched participants from the general population. The risk of developing lumbar HIVD among dentists, non‐dentist HCPs, and general population was compared by tracing their medical histories between 2007 and 2011. Results The cumulative incidence rate of lumbar HIVD among dentists during the 5‐year follow‐up period was 1.40%. After adjusting for age, gender, and comorbidities, the risk of developing lumbar HIVD was found to be lower among dentists than that among the general population (adjusted odds ratio [AOR]: 0.80, 95% confidence interval [CI]: 0.64‐1.00) and non‐dentist HCPs (AOR: 0.81, 95% CI: 0.68‐0.96). Conclusions Dentists in Taiwan have a lower risk of developing lumbar HIVD than that among other occupations. Although this result is different from the general cognition, it does not imply that the prevention of lumbar HIVD in dentists is not important. Further studies are warranted to better address this issue.

Background Kidney transplantation (KT) has been found to reduce cardiovascular events and mortality in chronic dialysis patients. There is little data, however, regarding the risk reduction of cerebrovascular events after KT in Asian populations. This study evaluates the risk of cerebrovascular events after KT in Taiwan. Methods Tapping Taiwan’s National Health Insurance claims data of patients with a diagnosis of end-stage renal disease (ESRD), we enrolled all KT recipients from 1999 to 2011 (n = 2908). For each KT patient, four controls (patients also diagnosed with ESRD) without KT were propensity matched by birth date, sex, selected comorbidities and duration of dialysis. All subjects were followed to the end of 2011. Results The incidence rate for stroke in the KT recipients and comparison group were 52.63 and 137.26 per 10 000 person-years, respectively. After adjustment for age, gender and comorbidities with competing mortality, KT recipients had 60% reduction in all kinds of stroke, compared to those who did not receive procedure. They were found to have a 48 and 74% reduction in ischemic and hemorrhagic stroke risk, respectively. Subgroup analyses also showed similar trends in the improvement of stroke after KT. While elderly patients, men, and those with diabetes, hypertension and coronary artery disease are at increased risk for stroke, our log-rank test revealed those that received KT had significantly lower cumulative incidence rates of stroke than those that did not (P Conclusions KT was associated with reduced risk of new onset stroke in chronic dialysis patients in Taiwan.

Diabetes mellitus (DM) is a known risk factor for dementia. It is unclear whether diabetic ketoacidosis (DKA) further increases the risk of dementia in patients with type 2 DM.This retrospective nationwide population-based cohort study was conducted using Taiwan's National Health Insurance database. We extracted claims data for 4451 patients with type 2 diabetes and DKA and 8902 diabetic controls matched for age, gender, diabetes complication severity index, frequency of clinic visits and baseline comorbidities between 2000 and 2002. Patients with type 1 diabetes or prior hypoglycemia before index date were excluded. All patients were tracked until new dementia diagnosis, death, or end of 2011.Of the 4451 DKA patients, 211 (4.7%) and 305 (3.4%) of the 8902 diabetic controls were diagnosed as having dementia during the follow-up period. The incidence rate ratio (IRR) for dementia was 1.62 (95% CI 1.35-1.93; P 0.0001) for patients with DKA versus diabetic patients without DKA. After adjusting for age, baseline comorbidities, geographic area, and income, patients with DKA were found to have 1.86 times the risk of developing dementia, compared to controls (95% CI 1.56-2.22, P 0.0001). They were found to have a higher risk of Alzheimer's dementia (HR:1.86; 95% CI 1.52-2.28, P 0.0001) but not non-Alzheimer's dementia.Type 2 diabetes patients with DKA are at increased risk of Alzheimer's dementia but not non-Alzheimer dementia.

This retrospective, nationwide, matched cohort study investigated the temporal relationship of central serous chorioretinopathy (CSCR) following topical ophthalmic corticosteroid (TOC) use. Using the Longitudinal Health Insurance Database 2000 (LHID2000), we collected patients diagnosed with CSCR between January 2001 and December 2010 (n&thinsp, = &thinsp, 2921) and a control group (n&thinsp, 17,526). Information for each patient was collected and tracked from the index date until December 2011. TOC users were classified based on (i) the date of the last prescription before diagnosis: current users (&le, 30 days) and former users (31&ndash, 182 days and &ge, 183 days) and (ii) the prescription refill intervals: persistent users (interval &le, 90 days) and non-persistent users (interval &gt, 90 days). The odds ratio (OR) was estimated from multivariate conditional logistic regression after adjusting for relevant confounders. After adjusting for age, sex, geographic region, index date, previously known comorbidities, the date of last TOC prescription before diagnosis, or prescription refilling intervals, the results revealed that patients were likely to have developed CSCR while using TOCs currently (OR = 30.42, 95% CI = 25.95&ndash, 35.66, p &lt, 0.001) and persistently (OR = 7.30, 95% CI = 6.13&ndash, 8.69, p &lt, 0.001) as compared to the controls. Our results indicate that current or persistent TOCs use increases the risk of CSCR. Thus, patients requiring TOCs should be advised of this risk, particularly in current or persistent use conditions.

This retrospective, nationwide, matched-cohort study included 4488 new-onset keratoconus (KCN) patients, &ge, 12 years old, recruited between 2004 and 2011 from the Taiwan National Health Insurance Research Database. The control group included 26,928 non-KCN patients selected from the Taiwan Longitudinal Health Insurance Database 2000. Information for each patient was collected and tracked from the index date until December 2013. The incidence rate of mitral valve prolapse (MVP) was 1.77 times (95% confidence interval (CI) = 1.09&ndash, 2.88, p = 0.0206) higher in KCN patients &ge, 40 years old and 1.49 times (95% CI = 1.12&ndash, 1.98, p = 0.0060) higher in female KCN patients than in controls. After using the Cox proportional hazard regression analysis to adjust for potential confounders, including hypertension, hyperlipidemia, and congestive heart failure, KCN maintained an independent risk factor, MVP being 1.77 times (adjusted hazard ratio (HR) = 1.77, 95% CI = 1.09&ndash, 2.88) and 1.48 times (adjusted HR = 1.48, 95% CI = 1.11&ndash, 1.97) more likely to develop in patients &ge, 40 years old and female patients in the study cohort, respectively. We found that KCN patients &ge, 40 years of age and female KCN patients have increased risks of MVP. Therefore, it is recommended that KCN patients should be alerted to MVP.

Background: Both keratoconus (KCN) and chronic kidney disease (CKD) are multifactorial conditions with multiple aetiologies and share several common pathophysiologies. However, the few studies that have described the relationship between KCN and CKD are limited to case reports and small case series. This study aimed to evaluate the association between KCN and CKD.Methods: The study cohort included 4,609 new-onset keratoconus patients ≥ 12 years identified by the International Classification of Diseases, Ninth Revision, Clinical Modification, code 371.6 and recruited between 2004 and 2011 from the Taiwan National Health Insurance Research Database. The age- , sex- , and comorbidity-matched control group included 27,654 non-KCN patients, selected from the Taiwan Longitudinal Health Insurance Database, 2000. Information for each patient was collected and tracked from the index date until December 2013. The incidence and risk of CKD were compared between the two groups. The adjusted hazard ratios (HRs) for CKD were calculated with Cox proportional hazard regression analysis. Kaplan–Meier analysis was used to calculate the cumulative CKD incidence rate. Results: The incidence rate of CKD was 1.36 times higher in KCN patients than in controls without statistically significant difference (95% confidence interval [CI] = 0.99–1.86, p = 0.06). In total, 29 male KCN patients and 90 controls developed CKD during the follow-up period. The incidence rate of CKD was 1.92 times (95% [CI] = 1.26–2.91; p = 0.002) higher in male KCN patients than in controls. After adjusting for potential confounders, including hypertension, hyperlipidaemia, and diabetes mellitus, male KCN patients and male patients ≥ 40 years were 1.75 times (adjusted HR = 1.75, 95% [CI] = 1.14–2.68, p < 0.05), and 19.83 times (adjusted HR = 19.83, 95% CI = 8.75–44.97, p < 0.05) more likely to develop CKD, respectively. Conclusions: We found that male KCN patients, particular male patients ≥ 40 years of age have an increased risk of CKD. Therefore, it is recommended that male KCN patients should be aware of CKD.

Despite the numerous risk factors for atherosclerotic cardiovascular diseases (ASCVD), cumulative evidence shows that electronegative low-density lipoprotein (L5 LDL) cholesterol is a promising biomarker. Its toxicity may contribute to atherothrombotic events. Notably, plasma L5 LDL levels positively correlate with the increasing severity of cardiovascular diseases. In contrast, traditional markers such as LDL-cholesterol and triglyceride are the therapeutic goals in secondary prevention for ASCVD, but that is controversial in primary prevention for patients with low risk. In this review, we point out the clinical significance and pathophysiological mechanisms of L5 LDL, and the clinical applications of L5 LDL levels in ASCVD can be confidently addressed. Based on the previously defined cut-off value by receiver operating characteristic curve, the acceptable physiological range of L5 concentration is proposed to be below 1.7 mg/dL. When L5 LDL level surpass this threshold, clinically relevant ASCVD might be present, and further exams such as carotid intima-media thickness, pulse wave velocity, exercise stress test, or multidetector computed tomography are required. Notably, the ultimate goal of L5 LDL concentration is lower than 1.7 mg/dL. Instead, with L5 LDL greater than 1.7 mg/dL, lipid-lowering treatment may be required, including statin, ezetimibe or PCSK9 inhibitor, regardless of the low-density lipoprotein cholesterol (LDL-C) level. Since L5 LDL could be a promising biomarker, we propose that a high throughput, clinically feasible methodology is urgently required not only for conducting a prospective, large population study but for developing therapeutics strategies to decrease L5 LDL in the blood.

PURPOSE To investigate the risk of keratoconus (KCN) in patients with atopic keratoconjunctivitis (AKC). METHODS This nationwide, retrospective, matched cohort study included 186 202 newly diagnosed AKC patients who were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), code 372.05, and selected from the Taiwan National Health Insurance Research Database. The age- and sex-matched control group included 186 202 non-AKC patients selected from the Taiwan Longitudinal Health Insurance Database 2000. Patient information was collected between 1 January 2004 and 31 December 2011, and both groups of patients were tracked from the index date until December 2013. The incidence and risk of KCN (ICD-9-CM, code 371.6) were compared between the groups. A Cox proportional hazard regression analysis was performed to obtain the adjusted hazard ratio (HR) for KCN. The cumulative KCN incidence rate was calculated with the Kaplan-Meier analysis. RESULTS In total, 62 AKC patients and 26 controls developed KCN during the follow-up period. The incidence rate of KCN was 2.49 times (95% confidence interval [CI] = 1.57-3.93; p

AimsTo investigate the risk of corneal ulcer in patients with atopic keratoconjunctivitis (AKC).MethodsThe nationwide, population-based, retrospective, matched cohort study included 171 019 newly diagnosed patients with AKC who were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), code 372.05, and selected from the Taiwan National Health Insurance Research Database. The age-, sex- and potential comorbidities-matched control group included 171 019 patients with non-AKC selected from the Taiwan Longitudinal Health Insurance Database 2000. Patient information was collected between 1 January 2004 and 31 December 2011, and both groups of patients were tracked from the index date until December 2013. The incidence and risk of corneal ulcer (ICD-9-CM code 370.0 except for 370.07) was compared between the groups. A Cox proportional hazard regression analysis was performed to obtain the adjusted HR for corneal ulcer. The cumulative corneal ulcer incidence rate was calculated with the Kaplan-Meier analysis.ResultsIn total, 2018 patients with AKC and 1481 controls developed a corneal ulcer during the follow-up period. The incidence rate of corneal ulcer was 1.42 times (95% CI1.33 to 1.52; pConclusionsPatients with AKC had an increased risk of developing a corneal ulcer and should be advised of this risk.

Background Whether nonobstetric surgery during gestation is associated with a higher risk of spontaneous abortion or adverse delivery outcomes is still unclear. Methods We performed a retrospective case-control study using a Longitudinal Health Insurance Database (LHID 2000) containing claim-data of 1 million randomly selected beneficiaries. We compared the incidences and estimated the adjusted odds ratios (aOR) with 95% confidence interval (95% CI) for spontaneous abortion, adverse delivery outcomes, cesarean delivery, and prolonged hospital stay to determine the risk of adverse outcomes in women who had nonobstetric surgery during gestation as compared to those who did not have any surgery during gestation. Results After exclusion, we were left with 114,852 delivery and 3999 abortion cases in our study; and 462 (0.39%) of them had nonobstetric surgery under general or regional anesthesia during pregnancy. The leading surgeries were repair of cervical os (33.12%), appendectomy (17.32%), ovarian surgeries (13.64%), and fixation of fractured bone (8.01%).The risk of spontaneous abortion (4.23% vs. 2.43%, aOR:1.53; 95% CI: 1.01–2.31), antepartum hemorrhage (7.14% vs. 2.83%, aOR: 2.51; 95% CI: 1.74–3.61), pre-eclampsia/eclampsia (2.60% vs. 1.01%, aOR: 2.35; 95% CI: 1.30–4.23), gestational diabetes (2.38% vs. 0.69%, aOR: 3.12; 95% CI: 1.69–5.78), prematurity (9.06 vs. 4.90%, aOR: 3.31; 95% CI: 2.54–4.31), cesarean section (43.55% vs. 33.76%, aOR: 1.41; 95% CI: 1.17–1.71), and prolonged hospital stay (1.82% vs. 5.91%, aOR: 3.23; 95% CI: 2.16–4.83) were higher in those women who had nonobstetric surgery after adjusting for age and comorbidities. Conclusions Nonobstetric surgery during gestation were associated with a higher risk of spontaneous abortion, adverse delivery outcomes, cesarean section, and prolonged hospital stay.

Background: Patients with either osteoporosis or depression are prone to develop other diseases and require more medical resources than do the general population. However, there are no studies on health-related quality of life (HRQoL) and medical resource use by osteoporosis patients with comorbid depression. We conducted this study for clarifying it. Methods: This cross-sectional study from 2005 to 2010 (6 years) analyzed 9776 National Health and Nutrition Examination Survey (NHANES) patients &gt, 40 years old. Each patient was assigned to one of four groups: osteoporosis-positive(+) and depression-positive(+) (O+/D+), O+/D&minus, O&minus, /D+, /D&minus, We used multivariate linear and logistic regression model to analyze the HRQoL and medical resource use between groups. Results: The O+/D+ group reported more unhealthy days of physical health, more unhealthy days of mental health, and more inactive days during a specified 30 days. The adjusted odds ratios (AORs) of O+/D+ patients who had poor general health (7.40, 95% CI = 4.80&ndash, 11.40), who needed healthcare (3.25, 95% CI = 2.12&ndash, 5.00), and who had been hospitalized overnight (2.71, 95% CI = 1.89&ndash, 3.90) were significantly highest. Conclusions: Low HRQoL was significantly more prevalent in D+/O+ patients. We found that depression severity more significantly affected HRQoL than did osteoporosis. However, both diseases significantly increased the risk of high medical resource use.

Objective Although inguinal hernia and aortic aneurysm share similar pathogenic mechanisms of collagen and elastin destruction, their clinical association in geriatric patients is inconclusive. We assessed the association between hernia and the subsequent occurrence of aortic aneurysm in geriatric patients. Methods Adult patients with hernias between 2000 and 2012 were identified from a longitudinal claims database of 1 million beneficiaries from Taiwan's National Health Insurance program, and a control group of patients without hernia were matched by propensity score in a ratio of 1:3. Patients previously diagnosed with aortic aneurysms or connective tissue diseases were excluded. Follow-up ended on December 31, 2013. The incidence rate of aortic aneurysm was compared between patients with hernia and those without. Cox proportional hazards models were used to estimate relative hazards. Results After propensity score matching, there were 16,933 patients with hernia (aged 20-64 years: 10,326; ≥65 years: 6607) and 50,799 patients without hernia (aged 20-64: 30,978; ≥65: 19,821). Patients with hernia had a greater incidence rate and hazard ratio of aortic aneurysm than did patients without hernia (6.4 vs 4.8/10,000 person-years; adjusted subdistribution hazard ratio [sdHR], 1.34; 95% confidence interval [CI], 1.02-1.76; P = .03), especially for those aged ≥65 years (15.6 vs 10.4/10,000 person-years; adjusted sdHR, 1.44; 95% CI, 1.07-1.94; P = .01) In addition, geriatric patients with hernia were associated with a marginally greater risk of thoracic (adjusted sdHR, 1.66; 95% CI, 0.96-2.86) and abdominal (adjusted sdHR, 1.36; 95% CI, 0.96-1.94) aortic aneurysm rupture. Conclusions Geriatric patients with hernia were associated with a greater incidence of aortic aneurysm than were those without.

Stroke and brain cancer are two distinct diseases. However, the relationship between both diseases has rarely been examined. This study investigated the longitudinal risk for developing brain cancer in stroke patients. To study this, we first reviewed the malignant gliomas previously with or without stroke using brain magnetic resonance imaging (MRI) images and the past histories. Two ischemic stroke patients before the malignant glioma were identified and belonged to the glioblastoma mutiforme (GBM). Particularly, both GBM specimens displayed strong hypoxia-inducible factor 1α (HIF-1α) expression in immunohistochemical (IHC) staining. To elucidate the significance of this relationship, we then used a nationwide population-based cohort in Taiwan to investigate the risk for the incidence of brain cancer in patients previously with or without stroke. The incidence of all tumors in the stroke group was lower than that in the control group with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI]: 0.74-0.84) in both gender and age older than 60 years. But the stroke patients had higher risk of developing only brain cancer with an adjusted HR of 3.09 (95% CI: 1.80-5.30), and otherwise had lower risk of developing head and neck, digestive, respiratory, bone and skin, as well as other tumors, all with p

Background/AimsTo investigate the risk of corneal ulcer in patients with end-stage renal disease (ESRD).MethodsThis retrospective, nationwide, matched cohort study included 92 967 patients with ESRD recruited between 2000 and 2009 from the Taiwan National Health Insurance Research Database. The same number of age-matched and sex-matched patients without ESRD were selected from the Taiwan Longitudinal Health Insurance Database, 2000 as the control group. Data for each patient were collected from the index date until December 2011. Corneal ulcer incidence rate and risk were compared between the groups. A Cox proportional hazards regression was used to calculate the HR for a corneal ulcer after adjustment for potential confounders. The cumulative corneal ulcer incidence rate was calculated using Kaplan-Meier analysis.ResultsIn total, 660 patients with ESRD and 591 controls showed a corneal ulcer during follow-up; thus, the corneal ulcer incidence rate in patients with ESRD was 1.54 times (95% CI 1.38–1.72) that in the control patients. After adjustment for potential confounders, including diabetes mellitus and HIV disease, patients with ESRD were 1.17 times (95% CI 1.03 to 1.33) more likely to develop a corneal ulcer in the cohort for the total sample. Among patients with diabetes mellitus, the corneal ulcer incidence rate was significantly higher in the ESRD group, and diabetes mellitus significantly increased corneal ulcer risk even after adjustment for other confounders in the cohort.ConclusionESRD increases the risk of a corneal ulcer, particularly in patients with ESRD with diabetes mellitus. Regular ocular examinations are suggested for patients with ESRD.

Background The elderly are predisposed to septic arthritis (SA) because of the aging nature and increasing comorbidities. SA may in turn increase the long-term mortality in the geriatric patients; however, it remains unclear. We conducted this prospective nationwide population-based cohort study to clarify this issue. Methods Using Taiwan National Health Insurance Research Database (NHIRD), we identified 1667 geriatric participants (≥ 65 years) with SA and 16,670 geriatric participants without SA matched at a ratio of 1:10 by age, sex, and index date between 1999 and 2010. A comparison of the long-term mortality between the two cohorts through follow-up until 2011 was performed. Results Geriatric participants with SA had a significantly increased mortality than those without SA [Adjusted hazard ratio (AHR): 1.49, 95% confidence interval (CI): 1.34–1.66], particularly the old elderly (≥ 85 years, AHR: 2.12, 95% CI: 1.58–2.84) and males (AHR: 1.54, 95% CI: 1.33–1.79). These results were stated after adjustment for osteoarthritis, diabetes, gout, renal disease, liver disease, cancer, rheumatoid arthritis, systemic lupus erythematosus, alcoholism, and human immunodeficiency virus infection. The increased mortality risk was highest in the first month (AHR: 3.93, 95% CI: 2.94–5.25) and remained increased even after following up for 2–4 years (AHR: 1.30, 95% CI: 1.03–1.65). After Cox proportional hazard regression analysis, SA (AHR: 1.37, 95% CI: 1.20–1.56), older age (≥ 85 years, AHR: 1.79, 95% CI: 1.59–2.02, 75–84 years, AHR: 1.65, 95% CI: 1.53–1.78), male sex, diabetes, renal disease, liver disease, cancer, and gout were independent mortality predictors. There was no significant difference in the mortality for SA between upper limb affected and lower limb affected. Conclusions This study delineated that SA significantly increased the long-term mortality in geriatric participants. For the increasing aging population worldwide, strategies for the prevention and treatment of SA and concomitant control of comorbidities are very important.

The incidence and mortality of site-specific cancers in patients with end-stage renal disease (ESRD) on maintenance dialysis have been rarely studied for Asian populations. We tapped Taiwan`s National Health Insurance Research Database to identify and recruit patients starting maintenance dialysis between 1999 and 2004. They were followed from initiation of dialysis until death, discontinuation of dialysis, or the end of 2008. We calculated the survival rate and mortality risk of dialysis patients with cancer. Of 40,833 dialysis patients, 2352 (5.8%) had been newly diagnosed with cancer. Being older, being male, and having chronic liver disease were factors associated with a higher risk for new cancer in ESRD dialysis patients. In men, liver cancer (20.63%) was the most frequent, followed by cancers of the bladder (16.88%) and kidney (11.61%). In women, bladder cancer (25.57%) was the most frequent, followed by cancers of the kidney (16.31%) and breast (11.20%). The 5-year survival rates for kidney and bladder cancer were higher than for other cancers; the survival rates for lung, stomach, and liver cancer were lower. In conclusion, the distribution of site-specific cancer was different between men and women in patients with ESRD on dialysis. More attention should be paid to teaching dialysis patients how to avoid the well-known cancer risks and carcinogens and individualized regular cancer screenings.

Background Prolonged static postures (PSPs) may predispose dentists to develop cervical herniated intervertebral disc (C-HIVD); however, there is limited evidence supporting this in the literature thus far. We conducted this study to fit the data gap. Methods We conducted a retrospective nationwide population-based study using the Taiwan National Health Insurance Research Database to identify 10,930 dentists, an identical number of age- and sex-matched participants from the general population, and 73,718 other health care providers (HCPs, non-dentists). Comparisons for the risk of developing C-HIVD between dentists and the general population, and between dentists and other HCPs were performed by tracing their medical histories between 2007 and 2011. Results Dentists had a cumulative incidence rate of 1.1% for C-HIVD during the 5-year follow-up period. Overall, there was no difference of the risk for C-HIVD between dentists and the general population after adjusting for hypertension, hyperlipidemia, liver disease, mental disorders, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease, malignancy, stroke, and renal disease (adjusted odds ratio [AOR]: 1.2, 95% confidence interval [CI]: 0.9–1.6). However, stratified analysis showed that younger dentists (≤ 34 years) had a trend of higher risk for C-HIVD than members of the younger general population (AOR: 1.9, 95% CI: 0.9–4.1). There was no difference found between dentists and other HCPs (AOR: 0.9, 95% CI: 0.8–1.1). Conclusion Younger dentists had a trend of higher risk of developing C-HIVD than members of the general population.

This study aimed to understand the changes and correlation in the long-term trends of polypharmacy and the utilization of health care services in a population over the age of 50 years through the use of a national database. A total of 2813 subjects who participated in surveys in 1999, 2003, and 2007 were selected as the samples. Each subject was followed-up for the period of 9 years. From 1999 to 2007, the proportion of mild and severe polypharmacy cases increased from 41.5% (1999) to 51.3% (2003) and 57.1% (2007), respectively. This study found that the more severe the polypharmacy was, the higher the risk of health care service utilization would be. The Generalized Estimating Equation model of multivariate analysis showed that the incidence rate ratio of medical utilization increased with the severity of polypharmacy, as did the use of advanced medical resources (ie, the number of hospitalizations). In particular, the increase in incidence rate ratio was more significant in 3 aspects: (1) number of pharmacy visits; (2) number of emergency room admissions; and (3) number of hospitalizations. The government should establish policies and guidance for the safe use of medicines to ensure reduced risk for older people.

Objective This study investigated the healthcare service utilisation and expenditure of patients with type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) and identified associated factors. Methods Healthcare service utilisation and expenditure of patients with T2DM with and without MDD during 2002–2013 were examined using Taiwan's population-based National Health Insurance claims database. Healthcare service utilisation included outpatient visits and inpatient admissions, and health expenditure included outpatient, inpatient, and total medical expenditure. Moreover, non-psychiatric health service utilisation and expenditure were distinguished from total health service utilisation and medical expenditure. Results Average healthcare service utilisation was significantly higher in those with comorbid MDD (both total and non-psychiatric utilisation). The higher overall costs of the patients with comorbid MDD largely driven by psychiatric costs and non-psychiatric costs between the groups were not significantly different. Gender, age, income, comorbidities and complications, and diabetes complications severity index were significant factors in outpatient visits, medical expenditure, and hospitalisation in those with comorbid MDD. Conclusions Type 2 diabetes patients with comorbid MDD were found to have higher costs, and that they appeared to be driven by more visits in the first 6 years and by psychiatric-related costs rather than general medical costs.

Background The long-term mortality of acetaminophen (APAP) poisoning has not yet been well studied; hence, we conducted this study to gain understanding of this issue. Methods We conducted a nationwide population-based cohort study by identifying 3235 participants with APAP poisoning and 9705 participants without APAP poisoning in Taiwan between 2003 and 2012 in the Nationwide Poisoning Database and Longitudinal Health Insurance Database 2000. Participants with APAP poisoning and control subjects were compared for the risk of all-cause mortality by follow-up until 2013. Results Two hundred forty-one participants with APAP poisoning (7.5%) and ninety-four control subjects (1.0%) died during the follow-up. Participants with APAP poisoning had a higher risk of all-cause mortality than the control subjects (incidence rate ratio [IRR], 8.1; 95% confidence interval [CI], 6.3–10.2), especially in the subgroup aged 20 years and younger (IRR, 27.3; 95% CI, 3.5–215.5) and in the first 12 months after poisoning (IRR, 16.0; 95% CI, 9.9–25.7). The increased risk of all-cause mortality was found even up to 2 years after the index poisoning. Conclusion APAP poisoning was associated with increased long-term mortality. Early referral for intensive aftercare and associated interventions are suggested; however, further studies of the method are needed for clarification.

Objective. To investigate the subsequent risks of urinary tract cancers among individuals with bladder pain syndrome/interstitial cystitis (BPS/IC), and gender differences, as well as the effect of associated comorbidity using a population-based administrative database in Taiwan. Patients and Methods. BPS/IC subjects (10192) and their age- and sex-matched non-BPS/IC control subjects (30576), who had no previous upper urinary tract cancer (UUC), bladder cancer (BC), and prostate cancer (PC), subsequently developed these disorders from the recruited date between 2002 and 2008 and the end of follow-up 2011. A Cox proportional hazards regression model was constructed to estimate the risk of subsequent UUC, BC, and PC following a diagnosis of IC/BPS. The effect of associated comorbidities was measured by Charlson Comorbidity Index (CCI). The risk of outcomes was assessed with Kaplan-Meier curves. Results. In the BPS/IC subjects, 37 (0.36%) received a diagnosis of BC, and 22 (0.22%) received a diagnosis of UUC; both were significantly higher than the control group, 19 (0.06%) for BC and 30 (0.10%) for UUC. Cox proportional analysis revealed that the adjusted HR for BC and UUC during the follow-up period for patients with IC/BPS was 5.44 (95% CI: 3.10-9.54) and 1.97 (95% CI: 1.13-3.45) than that of comparison subjects. The HRs went up to 5.66 (95% CI: 3.21-9.99) and 2.01 (95% CI: 1.14-3.55) after adjusted by Comorbidity Index (CCI). The male BPS/IC patients have a higher adjusted HR for BC; however, female patients have a higher adjusted HR for both BC and UUC. The adjusted HR for PC has no difference between BPS/IC and control group. Conclusion. Patients with BPS/IC are at risk of developing BC in both males and females, and UUC in females. This result reminds physicians to evaluate the potential risk of subsequent development of BC and UUC among individuals with BPS/IC.

Background: The effects of the mode of anesthesia on major adverse postoperative outcomes in geriatric patients are still inconclusive. The authors hypothesized that a neuraxial anesthetic (NA) rather than a general anesthetic (GA) would yield better in-hospital postoperative outcomes for geriatric patients undergoing hip surgery. Methods: The authors used data from Taiwan’s 1997–2011 in-patient claims database to evaluate the effect of anesthesia on in-hospital outcomes. The endpoints were mortality, stroke, transient ischemic stroke, myocardial infarction, respiratory failure, and renal failure. Of the 182,307 geriatric patients who had hip surgery, a GA was given to 53,425 (29.30%) and an NA to 128,882 (70.70%). To adjust for baseline differences and selection bias, patients were matched on propensity scores, which left 52,044 GA and 52,044 NA patients. Results: GA-group patients had a greater percentage and higher odds of adverse in-hospital outcomes than did NA-group patients: death (2.62 vs. 2.13%; odds ratio [OR], 1.24; 95% CI, 1.15 to 1.35; P < 0.001), stroke (1.61 vs. 1.38%; OR, 1.18, 95% CI, 1.07 to 1.31; P = 0.001), respiratory failure (1.67 vs. 0.63%; OR, 2.71; 95% CI, 2.38 to 3.01; P < 0.001), and intensive care unit admission (11.03 vs. 6.16%; OR, 1.95; 95% CI, 1.87 to 2.05; P < 0.001), analyzed using conditional logistic regression. Moreover, patients given a GA had longer hospital stays (10.77 ± 8.23 vs. 10.44 ± 6.67 days; 95% CI, 0.22 to 0.40; P < 0.001) and higher costs (New Taiwan Dollars [NT$] 86,606 ± NT$74,162 vs. NT$74,494 ± NT$45,264; 95% CI, 11,366 to 12,859; P < 0.001). Conclusion: For geriatric patients undergoing hip surgery, NA was associated with fewer odds of adverse outcomes than GA.

Hyperglycemic crisis episodes (HCEs)—diabetic ketoacidosis and the hyperosmolar hyperglycemic state—are the most serious acute metabolic complications of diabetes. We aimed to investigate the subsequent mortality after HCE in the non-elderly diabetic which is still unclear. This retrospective national population-based cohort study reviewed, in Taiwan’s National Health Insurance Research Database, data from 23,079 non-elder patients (≤65 years) with new-onset diabetes between 2000 and 2002: 7693 patients with HCE and 15,386 patients without HCE (1:2). Both groups were compared, and follow-up prognoses were done until 2011. One thousand eighty-five (14.1 %) patients with HCE and 725 (4.71 %) patients without HCE died (P

Previous studies have reported an increased prevalence of sudden sensorineural hearing loss (SSNHL) in osteoporotic patients. However, the risk of SSNHL in this population remains unclear.This study investigated the risk of SSNHL in osteoporotic patients.Taiwan launched a single-payer National Health Insurance (NHI) program on March 1, 1995. NHI covers nearly all of Taiwan's residents.Using randomized representative sample of one million individuals from Taiwan's National Health Insurance claims database, we compared the data of 10,660 patients with newly diagnosed osteoporosis from 1998-2008 and with 31,980 patients without osteoporosis. All patients were tracked until SSNHL was diagnosed, death, or the end of 2011. Osteoporosis was identified based on a primary diagnosis of osteoporosis (ICD-9-CM code 7330) by dual-energy x-ray absorptiometry.Identified the diagnosis of osteoporosis and SSNHL by ICD-9CM code.The identification of patients with newly diagnosed SSNHL by ICD-9CM code.The incidence rates of SSNHL in the osteoporosis cohort and comparison group were 10.43 and 5.93 per 10,000 person years. Patients with osteoporosis were at 1.76 times the risk of developing SSNHL than patients without osteoporosis. The incidence rate ratio (IRR) for SSNHL was significantly greater in older (50-64 y and ≥ 65 y), and female patients, and borderline greater in hypertensive patients with osteoporosis than the controls, IRRs being 1.50, 2.33, 1.87, and 1.59.Patients with osteoporosis are at significantly greater risk of developing SSNHL.

BACKGROUND High urologic malignancy incidence has been reported in end-stage renal disease (ESRD) patients, especially of female sex. This study was undertaken to evaluate whether female recipients still carry an aggravated risk of this malignancy after kidney transplantation (KT). METHODS The claims data from the Bureau of National Health Insurance of Taiwan were used for analysis. All KT recipients who developed urologic malignancy from January 1, 1999, to December 31, 2007 (n = 2,245) were enrolled in this study. By means of propensity score, a database of 1:4 ratio random incident ESRD patients with matched age, sex, comorbidity rates, and dialysis to index date was used as control (non-KT group, n = 8,980). The last observation period ended on December 31, 2008. RESULTS The cumulative urologic malignancy incidence rate was significantly higher in female recipients after KT than their female ESRD counterparts without KT (P < 0.001). This gap became more prominent approximately 2 years after transplantation. No similar trend was detected in male KT patients (P = 0.13). Incidence rate ratio of urologic malignancy was significantly higher in female recipients (incidence rate ratio, 2.13; 95% confidence interval [95% CI], 1.53-2.97) than in their male counterparts (incidence rate ratio, 1.43; 95% CI, 0.90-2.25). From multivariate Cox proportional hazard regression tests, female (hazards ratio, 2.10; 95% CI, 1.52-2.95) but not male sex (hazards ratio, 1.47; 95% CI, 0.93-2.32) was determined to be an independent factor for the development of urologic malignancy after KT. After acquiring this malignancy, KT recipients did not have any advantage in cumulative survival compared to ESRD patients without KT (P = 0.07). CONCLUSION Compared to males, female recipients tended to have a significantly higher urologic malignancy risk after KT.

Lower urinary tract symptoms (LUTS) have a negative impact on the quality of life, and may relate to anxiety and depression. The objective of this study was to test the hypothesis that LUTS are associated with anxiety and depression using a nationwide population-based database in Taiwan. Data were obtained from a random population sample of about one million enrollees in the National Health Insurance program from 2001 to 2009, and consisted of 22,980 LUTS patients and 45,960 matched controls. The records of healthcare seeking for anxiety and depression were collected 2 years before and after the diagnosis of LUTS. The results showed that patients with LUTS had a significantly higher prevalence of anxiety or depression than the matched controls (11.45% vs. 5.72%). After controlling for sociodemographic variables and other major systemic diseases, the odds ratios for anxiety, depression, either anxiety or depression, and both anxiety and depression, were 2.05, 2.19, 2.14, and 2.56, respectively. There was an association between LUTS and the stress-related common mental disorders, and there seemed to be an additive effect of anxiety and depression on the association with LUTS. These findings imply a psychological role in the pathogenesis or sequelae of LUTS.

To explore the association between bladder pain syndrome/interstitial cystitis (BPS/IC) and the risk of subsequent healthcare-seeking behavior for common mental disorders in Taiwan using a population-based administrative database. Both BPS/IC subjects and their age- and sex-matched non-BPS/IC control subjects who had no previous insomnia and mental diseases, including anxiety, depression, were subsequent serviced for these mental disorders by psychiatrists from the recruited date between 2002 and 2010. The risk of outcomes was assessed with Kaplan–Meier curves; and the impact of BPS/IC was estimated with Poisson regression analysis and Cox proportional hazards models. We included 16,185 BPS/IC subjects and 32,370 non-BPS/IC subjects, with a mean age of 46 years and 73.5 % of women. Difference of the prevalence of hypertension, diabetes, chronic kidney disease, and hyperlipidemia between groups was not significant difference. Subjects with BPS/IC had a significant higher incidence rate of anxiety, depression, and insomnia than the matched controls (92.9 vs 38.4, 101.0 vs 42.2, 47.5 vs 23.0; per 10,000 person-year). After adjusting for age, sex, and common comorbidities in multivariable analysis, BPS/IC remained a significant predictor with hazard ratio and 95 % confidence incidence, 2.4 (2.2–2.7), 2.4 (2.2–2.6), and 2.1 (1.8–2.4) for anxiety, depression, and insomnia, respectively. Patients with BPS/IC are at risk of development of anxiety, depression, and insomnia. These findings can help guide urologists, urogynecologists, and psychiatrists toward early identification and treatment of psychological complications that may develop in BPS/IC patients.

Background The incidence of infective endocarditis (IE) is high in dialysis patients. Limited data are available on the risk factors for IE and long-term outcome after IE in dialysis patients, especially in Asian populations. Methods We used Taiwan National Health Insurance Research Database to design a longitudinal cohort study. 68,426 ESRD patients who began dialysis between 1999 and 2007 were included. The follow-up period was from the start of dialysis to death, end of dialysis, or end of 2008. Cox proportional hazards models were used to identify the risk factors for IE. Results IE was diagnosed in 502 patients during follow-up (201.4 per 100,000person-years). Diabetes mellitus (DM), congestive heart failure (CHF), cerebro-vascular accident (CVA), and rheumatic heart disease (RHD) (HR: 3.07, 95% CI: 1.99–4.75) were associated with an increasing risk of development of IE. The cumulative incidence rate of IE in patients with RHD was 1.4, 2.2, and 3.9% at 1, 3, and 5years. In-hospital mortality was 23.5%. Cumulative survival rates post-IE were 54.3% at 1year and only 35.3% at 5years. Conclusion Dialysis patients had a higher risk of IE. Those who were older and had DM, CHF, CVA, or especially RHD were at a greater risk. Dialysis patients with IE also had high mortality.

To explore the recurrence rate of idiopathic sudden sensorineural hearing loss (ISSNHL).Using the Taiwan Longitudinal Health Insurance Database, we compared in a retrospective cohort study 45,715 patients with ISSNHL between January 2001 and December 2006 with 45,715 age-, gender-, and comorbidity-matched controls without ISSNHL. We followed each patient from 180 days after the initial diagnosis until the end of 2009 and evaluated the incidence of ISSNHL for 3 years minimum.The cumulative incidence of ISSNHL recurrence was 4.99%. Cox proportional hazard regressions showed that the 50- to 64-year-old age group had a higher adjusted hazard ratio (1.59; 95% confidence interval: 1.40-1.81) than did the 0- to 34-year-old age group. Different comorbidities did not significantly affect the incidence of ISSNHL relapse.The risk of an ISSNHL relapse in patients with a history of ISSNHL was higher than was the risk of a first occurrence of ISSNHL in the Controls. We suggest that physicians counsel patients with a history of ISSNHL to seek medical attention if they have hearing impairments because they may also have a high risk of an ISSNHL relapse.2B.

BACKGROUND Physicians in Taiwan work in stressful workplaces and have heavy workloads, both of which may contribute to the occurrence of a stroke. However, it is not clear whether they have a higher risk of stroke. Therefore, we conducted a population-based cohort study to compare the risks of stroke between physicians and the general population and among subgroups of physicians in Taiwan. METHODS In the National Health Insurance Research Database of Taiwan, we identified 28,062 physicians and selected 84,186 age- and sex-matched nonmedical staff beneficiaries as the references. Using conditional logistic regression, we compared the prevalence of stroke between physicians and references. In addition, we made comparisons among subgroup of physicians defined by age, sex, comorbidity, specialty, and the level of hospital. RESULTS During the study period, physicians had higher prevalence rates of hypertension (23.6% vs. 19.1%), hyperlipidemia (21.4% vs. 12.9%), and coronary artery disease (CAD) (6.4% vs. 5.7%) than the referent group, but they had a lower risk of stroke with an odds ratio of 0.61 (95% confidence interval = 0.55, 0.66) after adjusting for hypertension, diabetes, hyperlipidemia, CAD, and active worker. Among physicians, the risks were higher in those who were older or had hypertension, diabetes, hyperlipidemia, or CAD. CONCLUSIONS Despite having higher prevalence rates of hypertension, hyperlipidemia, and CAD and working in stressful workplaces with heavy workloads, our study suggests that physicians in Taiwan have a lower risk of stroke compared with the general population. These results may indicate the benefits of higher awareness and more knowledge of diseases.

The aim of this retrospective, nationwide, matched cohort study was to investigate the association of serous retinal detachment with having end-stage renal disease (ESRD) while on dialysis. The cohort study included 94,024 patients with ESRD on dialysis registered between January 2000 to December 2009 in the Taiwan National Health Insurance Research Database. An age- and sex-matched control group comprised 94,024 patients selected from the Taiwan Longitudinal Health Insurance Database 2000. Information for each patient was collected from the index date until December 2011. Twenty-seven ESRD patients and 11 controls developed serous retinal detachment (P < 0.001) during follow-up, demonstrating a significantly increased risk of serous retinal detachment in patients with ESRD on dialysis compared with controls (incidence rate ratio = 3.39, 95% confidence interval [CI] = 1.68-6.83). After adjustment for potential confounders, patients were 3.86 times more likely to develop serous retinal detachment than the full cohort (adjusted HR = 3.86, 95% CI = 1.15-12.96). In conclusion, patients with ESRD on dialysis demonstrate an increased risk of serous retinal detachment. Interdisciplinary collaboration between nephrologists and ophthalmologists is important to deal with serous retinal detachment in patients with ESRD on dialysis and prevent impairments of visual acuity.

Objective We investigated the longitudinal impacts of insomnia on the subsequent developments of anxiety and depression during a four-year follow-up. We further categorized individuals with insomnia into different insomnia subgroups to examine whether the risk of anxiety and depression varies by subtype. Methods Participants were identified from National Health Insurance enrollees in Taiwan during 2002–2009. The study included 19,273 subjects with insomnia and 38,546 matched subjects without insomnia. All subjects did not have previous diagnosis of insomnia, sleep apnea, anxiety, or depression. Results Compared with non-insomniacs, insomniacs had a higher risk of developing anxiety only [adjusted hazard ratio (HR) = 8.83, 95% CI = 7.59–10.27], depression only (adjusted HR = 8.48, 95% CI = 6.92–10.39), and both anxiety and depression (adjusted HR = 17.98, 95% CI = 12.65–25.56). When breaking down the insomnia subgroups, individuals with a relapse of insomnia (adjusted HR = 10.42–26.80) had the highest risk of anxiety only, depression only, and both anxiety and depression, followed by persistent insomnia (adjusted HR = 9.82–18.98), then remitted insomnia (adjusted HR = 4.50–8.27). All three insomnia subgroups had a greater four-year cumulative incidence rate than the non-insomnia group for anxiety only, depression only, and both anxiety and depression ( p Conclusion Our findings reinforce the clinical predictor role of insomnia in the future onset of anxiety or/and depression. Awareness of insomnia and treatment of insomnia should be recommended at clinics, and patterns of insomnia should be monitored to help treatment and control of subsequent psychiatric disorders. Future research with comprehensive data collection is needed to identify factors that contribute to different insomnia subtypes.

Objective: This study compared the risk of varicose veins (VV) among physicians, nonphysician health care providers (HCP), and the general population. Subjects and Methods: The Taiwan National Health Insurance Research Database was used to identify 28,844 physicians and 26,099 nonphysician HCP and an identical number of age- and sex-matched patients from the general population. Using logistic regression analyses, VV risks between physicians and the general population, nonphysician HCP and the general population, and physicians and nonphysician HCP, and among physician specialists were compared by tracing their medical histories between 2007 and 2011. Results: Physicians and nonphysician HCP had cumulative VV incidences of 0.12% (34/28,844) and 0.13% (33/26,099), respectively, during the 5-year period, compared to that of the general population within the same 5-year period. Physicians and nonphysician HCP did not have a higher VV risk than the general population after adjusting for deep vein thrombosis (DVT) history (adjusted odds ratio [AOR] 0.86; 95% confidence interval [CI] 0.53-1.40, and AOR 1.43; 95% CI 0.82-2.50, respectively). Physicians did not a have higher VV risk than nonphysician HCP (AOR 0.80; 95% CI 0.43-1.51) after adjusting for age, sex, and DVT history. Surgery had the highest incidence (0.22%) while pediatrics and emergency medicine had the lowest incidence (0%) of VV risk among physician specialists; however, the difference was not significant (all p values >0.05). Conclusion: In this study, VV risk did not differ among physicians, nonphysician HCP, and the general population.

Background Involutional blepharoptosis is the most common type of acquired blepharoptosis. The etiology is believed to be the degeneration of the levator aponeurosis, and levator superioris muscle function was believed to be normal. However, there are a few studies analyzing levator function (LF) in involutional blepharoptosis. Our study aimed to access the LF abnormality in involutional blepharoptosis and analyze the correlation between LF and ptosis severity in involutional blepharoptosis in Taiwan. Methods We reviewed the medical records of patients who underwent ptosis correction surgery between October 2011 and December 2015 after receiving a diagnosis of involutional blepharoptosis. This study examined patient sex and age, preoperative LF, margin reflex distance of the upper eyelid (MRD1), and ptosis severity. Linear regression was performed for statistical analysis. Levator muscle specimen was sent for pathologic examination. Results We analyzed 231 eyelids of 126 patients. Average MRD1 was 0.43 ± 2.15 mm. Average LF was 14.30 ± 2.51 mm. Overall, 77.1% (178/231) of involutional blepharoptotic eyelids had normal LF (more than 12 mm). Forty-three (18.6%) of 231 were good (10-12 mm), and 10 (4.3%) of 231 were fair (6-9 mm). No patients with poor levator function (≤5 mm) were observed in our case series. A positive correlation between LF and MRD1 was observed after statistical analysis. On average, a 0.6-mm reduction in LF was observed for each 1.0-mm decrease in MRD1. Fat infiltration in levator muscle is observed both grossly and microscopically in most cases with varied degrees. Conclusions Levator function and MRD1 were positively correlated in patients with involutional blepharoptosis. In our study, 77.1% (178/231) of eyelids had normal levator function, which meant there was 23.0% (53/231) of eyelids had abnormal LF, in contrast to current literature. Fat infiltration was common in our series. In Asian involutional blepharoptosis, LF was not always excellent and it had positive correlation with ptosis severity.

Background Diabetes is associated with development of end-stage renal disease (ESRD) dialysis, but it is not clear whether ESRD dialysis is a risk factor for new-onset diabetes (NODM). Methods Using the Taiwan National Health Insurance Research Database, we designed two cohort studies to determine the association between dialysis and diabetes. Analysis 1 estimated the hazard ratios (HR) of ESRD dialysis in 20,585 patients with type 2 diabetes (T2DM) and 82,340 gender- and age- matched controls without diabetes. Analysis 2 estimated the HRs of NODM in 18,489 ESRD patients undergoing dialysis and 73,956 gender- and age- matched controls without ESRD dialysis. The follow-up period was from 2000 to date of endpoint, the date of death, or December 31, 2008. Cox proportional models were used to estimate the relative hazards. Results In analysis 1, the incidence of ESRD dialysis was higher in the T2DM cohort than in the non-diabetes cohort (6.78 vs. 0.61 per 1,000 person-years; HR: 7.97; 95%CI: 7.05-8.00). In analysis 2, the incidence of NODM was higher in the ESRD dialysis cohort than in the without-ESRD dialysis cohort (22.84 vs. 13.99 per 1,000 person-years; HR: 1.40; 95% CI: 1.34-1.47). Conclusions ESRD dialysis and diabetes were bidirectionally associated. The relationship between T2DM and incident ESRD dialysis was much stronger than between ESRD dialysis and NODM. Further studies are needed to determine the mechanism of ESRD dialysis-related NODM.

Postherpetic neuralgia is the most common complication of herpes zoster. Identifying predictors for postherpetic neuralgia may help physicians screen herpes zoster patients at risk of postherpetic neuralgia and undertake preventive strategies. Peptic ulcer has been linked to immunological dysfunctions and malnutrition, both of which are predictors of postherpetic neuralgia. The aim of this retrospective case-control study was to determine whether adult herpes zoster patients with peptic ulcer were at greater risk of postherpetic neuralgia. Adult zoster patients without postherpetic neuralgia and postherpetic neuralgia patients were automatically selected from a medical center's electronic database using herpes zoster/postherpetic neuralgia ICD-9 codes supported with inclusion and exclusion criteria. Consequently, medical record review was performed to validate the diagnostic codes and all pertaining data including peptic ulcer, Helicobacter pylori (H. pylori) infection and ulcerogenic medications. Because no standard pain intensity measurement exists, opioid usage was used as a proxy measurement for moderate to severe pain. In total, 410 zoster patients without postherpetic neuralgia and 115 postherpetic neuralgia patients were included. Multivariate logistic regressions identified 60 years of age and older, peptic ulcer and greater acute herpetic pain as independent predictors for postherpetic neuralgia. Among etiologies of peptic ulcer, H. pylori infection and usage of non-selective nonsteroidal anti-inflammatory drugs were significantly associated with the increased risk of postherpetic neuralgia; conversely, other etiologies were not significantly associated with the postherpetic neuralgia risk. In conclusion, 60 years of age and older, peptic ulcer and greater acute herpetic pain are independent predictors for postherpetic neuralgia in adult herpes zoster patients. J. Med. Virol. 87:222–229, 2015. © 2014 Wiley Periodicals, Inc.

Aim To investigate the risk of acute coronary syndrome (ACS) following retinal artery occlusion (RAO). Methods The study cohort included all patients diagnosed with RAO between January 1999 and December 2008 (n=688) in the Taiwan Longitudinal Health Insurance Database 2000. The control group included randomly selected patients (n=4128) from the same database that were matched to the study group, using a propensity score, for age, gender, and comorbid diabetes mellitus, hypertension, hyperlipidaemia, chronic renal disease and atrial fibrillation status. The ACS-free survival rate was calculated using Kaplan–Meier analysis. Cox proportional hazard regression analysis was used to obtain the adjusted HR for ACS after adjustment for potential confounding factors. The incidence and risk of ACS were compared between the RAO and control groups. Results Thirty-seven patients in the RAO group (5.38%) and 138 controls (3.34%) had ACS (p=0.0063) during the follow-up period, resulting in a significantly higher risk of ACS in the RAO group (HR=1.67, 95% CI 1.16 to 2.40). After adjustment for potential confounders, the HR for developing ACS in the RAO group was 1.72 (95% CI 1.20 to 2.47) times higher than that of controls. When stratified by RAO type, the adjusted HR for ACS was 3.57 (95% CI 2.09 to 6.10) for the central RAO subgroup. Conclusions We found that RAO increased the risk for ACS. We recommend thorough follow-up cardiovascular examinations and medical prevention for ACS in patients following RAO.

Aims Using the National Health Insurance (NHI) database in Taiwan, the study aimed to evaluate the rates and associated factors for reoperation of female stress incontinence. Methods Records of female patients who had received a primary surgical treatment for stress incontinence from January 2000 to December 2006 were retrieved. Among these, patients who had reoperations during follow-up till December 2010 were identified. The data were analyzed for reoperation rates, surgery methods, patient demography, surgeon, and hospital attributes. Results Among 14,613 patients with a mean follow-up of 86.28 ± 26.76 months, 563 (3.85%) had reoperations, an incidence rate of 54.37 per 10,000 person year (PY). Injection procedures had the highest reoperation rate of 893.30/10,000 PY. The adjusted hazard ratio (HR) of reoperation was higher for mid-urethral sling when compared to pubovaginal sling (HR 1.54, 95% CI 1.16–2.05) or retropubic urethropexy including Burch operation (HR 1.30, 95% CI 1.04–1.61). Surgeons with high service volumes tended to have fewer reoperations. No correlations were noted between the reoperation rate with patient age, surgeon age/gender, year of operation and hospital status. However, urologists had higher reoperation rates than gynecologists. For repeat surgery, the majority of patients chose the same specialty but different surgical types. Mid-urethral sling was used most commonly in 48.85% of reoperations. Conclusions Substantial number of patients need reoperation for stress incontinence. The choice of primary surgery type and surgeon specialty may affect the reoperation rates. Mid-urethral sling is the most common reoperation choice. Neurourol. Urodynam. 34:???–???, 2015. © 2014 Wiley Periodicals, Inc.

Background The purpose of this study was to examine the effect of metformin on head and neck cancer in patients with diabetes. Methods We compared 66,600 patients, all with diabetes and all newly diagnosed with head and neck cancer in 2002. Half were being treated with metformin for diabetes (Met+) and half were not (Met−: controls). All were matched for comorbidities (obesity, coronary artery disease, hyperlipidemia, and hypertension), sex, and age. The risk of head and neck cancer at the end of 2011 was determined. Results The incidence of head and neck cancer was 34% lower in the Met+ cohort than in the Met− cohort (adjusted hazard ratio [HR] = 0.66; 95% confidence interval [CI] = 0.55–0.79). The risks for oropharyngeal cancer (adjusted HR = 0.66; 95% CI = 0.17–0.74) and nasopharyngeal carcinoma (NPC; adjusted HR = 0.50; 95% CI = 0.31–0.80) were significantly lower in the Met+ cohort than in the Met− cohort. Conclusion Metformin is associated with a lower risk of developing head and neck cancer in patients with diabetes. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1268–1273, 2015

Mechanical ventilation for preterm infants independently contributes to poor neurodevelopmental performance. However, few studies have investigated the association between the duration of mechanical ventilation and the risk for various developmental disorders in extremely low birth weight (ELBW) (

Background and Purpose— The studies assessing the impact of insomnia on stroke are still lacking. We aim to investigate insomnia in relation to subsequent stroke during the 4-year follow-up. Methods— Data from the Taiwan National Health Insurance Research Database were used. Enrollees with International Classification of Diseases, Ninth Revision , Clinical Modification diagnosis code for insomnia were compared with randomly selected, age- and sex-matched noninsomnia enrollees with subsequent hospitalization for stroke during the 4-year follow-up. All enrollees, insomniacs and noninsomniacs, did not have previous diagnosis of stroke, sleep apnea, and insomnia. Individuals with insomnia were further categorized into different subgroups based on their insomnia patterns to explore whether the risk of stroke varies by subtype. The risk of outcomes was assessed with Kaplan–Meier curves and the impact of insomnia was estimated using Poisson regression analysis and Cox proportional hazards models. Results— The study included 21 438 (mean age, 52±16 years) insomniacs and 64 314 matched noninsomniacs (mean age, 51±16 years). Compared with noninsomniacs, insomniacs had 54% higher risk of developing stroke (adjusted hazard ratio, 1.54; 95% confidence interval, 1.38–1.72). When breaking down into insomnia subgroups, the persistent insomniacs had a higher 3-year cumulative incidence rate of stroke than those in the remission group ( P =0.024). The insomniacs-to-noninsomniacs incidence rate ratio for stroke was highest among those aged 18 to 34 years (incidence rate ratio, 8.06). Conclusions— Insomnia predisposes individuals to increased risk of stroke and this association is profound among young adults. Our results underscore the clinical importance of identifying and treating insomnia. A novel behavioral intervention targeting insomnia that may prevent stroke should be explored.

Background and objects: We explored the relationship between hospital/surgeon volume and postoperative severe sepsis/graft-failure (including death). Methods: The Taiwan National Health Insurance Research Database claims data for all patients with end-stage renal disease patients who underwent kidney transplantation between January 1, 1999, and December 31, 2007, were reviewed. Surgeons and hospitals were categorized into two groups based on their patient volume. The two primary outcomes were severe sepsis and graft failure (including death). The logistical regressions were done to compute the Odds ratios (OR) of outcomes after adjusting for possible confounding factors. Kaplan-Meier analysis was used to calculate the cumulative survival rates of graft failure after kidney transplantation during follow-up (1999-2008). Results: The risk of developing severe sepsis in a hospital in which surgeons do little renal transplantation was significant (odds ratio [OR]; p = 0.0115): 1.65 times (95% CI: 1.12-2.42) higher than for a hospital in which surgeons do many. The same trend was true for hospitals with a low volume of renal transplantations (OR = 2.39; 95% CI: 1.62-3.52; p < 0.0001). The likelihood of a graft failure (including death) within one year for the low-volume surgeon group was 3.1 times higher than for the high-volume surgeon group (p < 0.0001); the trend was similar for hospital volume. Female patients had a lower risk than did male patients, and patients ≥ 55 years old and those with a higher Charlson comorbidity index score, had a higher risk of severe sepsis. Conclusions: We conclude that the risk of severe sepsis and graft failure (including death) is higher for patients treated in hospitals and by surgeons with a low volume of renal transplantations. Therefore, the health authorities should consider exporting best practices through educational outreach and regulation and then providing transparent information for public best interest.

This retrospective, nationwide, matched cohort study investigated the risk of central serous chorioretinopathy (CSCR) following end-stage renal disease (ESRD). The study cohort included 84722 ESRD patients who were registered between January 2000 and December 2009 at the Taiwan National Health Insurance Research Database. An age- and sex-matched control group comprised 84722 patients selected from the Taiwan Longitudinal Health Insurance Database 2000. We collected information for each patient from the index date until December 2011. During the follow-up period, we found a significantly elevated risk of CSCR in the ESRD patients compared with controls (incidence rate ratio = 1.51, 95% confidence interval = 1.24-1.84). After adjustment for potential confounders, including age, sex, coronary artery disease, peptic ulcer, and obstructive sleep apnea, ESRD patients were 1.41 times more likely to develop CSCR (adjusted hazard ratio = 1.41, 95% confidence interval = 1.14-1.73). In conclusion, we found that ESRD patients showed a significantly higher risk of developing CSCR and recommend regular retina examinations and education regarding CSCR for patients with ESRD.

Aims Epstein–Barr virus (EBV)-positive diffuse large B cell lymphoma (DLBCL) of the elderly is characterised by frequent extranodal involvement, a morphological spectrum from polymorphous to monomorphous and a poor prognosis. The frequency is higher in Japan and Korea but lower in the West, while the status in Taiwan has not been reported yet. Methods We conducted a retrospective study of DLBCL in a single institute in Taiwan by immunohistochemistry and in situ hybridisation for EBV. Results Of the 424 consecutive DLBCL cases, 332 cases were studied for EBV. 15 (4.5%) were EBV-positive and 13 (3.9%) fulfil WHO criteria of EBV-positive DLBCL of the elderly with a median age of 75. Of these 15 cases, extranodal presentation occurred in 11 (73%) patients with predominance in the gastrointestinal tract and 6 (40%) were of germinal centre B cell phenotype. There was no difference between EBV-positive and -negative patients in terms of age, gender, nodal versus extranodal presentation, and immunophenotypical profile. EBV-positive patients showed a trend for a shorter median survival time (5.0 vs 39.3 months; p=0.058). Of all DLBCL patients, multivariable analysis revealed a significantly worse overall survival for patients older than 50 (p=0.001) and for those with bcl-6-negative tumours (p=0.003) but not with other clinicopathological factors including EBV status. Conclusions EBV-positive DLBCL of the elderly is relatively rare in Taiwan, with an incidence intermediate between Japan/Korea and the West. Further studies are warranted to clarify the association of EBV and the clinicopathological features and the prognostic significance in patients with DLBCL.

Background Patients with end-stage renal disease (ESRD) on dialysis have poor outcomes after acute coronary syndrome (ACS). Epidemiological data for Asian patients are scarce. Methods This longitudinal cohort study investigated the incidence, risk factors, and outcomes of ACS in 19,974 ESRD incident dialysis patients in the Taiwan National Health Insurance research Database between January 1999 and December 2001. The follow-up period was from the start of dialysis to the date of death, end of dialysis, or December 31, 2008. Results ACS was diagnosed in 1785 patients during follow-up (1.78/100 person-years): 832 (46.6%) had acute myocardial infarction (AMI), 681 (38.2%) underwent cardiac catheterization, 398 (22.3%) underwent percutaneous transluminal coronary angioplasty (PTCA), and 50 (2.8%) underwent coronary artery bypass grafting. Male (HR 1.35, 95% CI: 1.23–1.49) and elderly (HR 3.289, 95% CI: 2.71–4.00) patients had a high rate of ACS. Patients with baseline comorbidities (diabetes mellitus, hypertension, congestive heart failure, coronary artery disease, dysrhythmia, and other cardiac and chronic obstructive lung diseases) had a higher incidence of ACS than did those without. Overall in-hospital mortality was 9.7%. The cumulative 6-month post-hospitalization survival rate was 79.3%; the 1-year rate was 72.3%. Being elderly (≥65years old), and having DM or AMI were associated with an increased risk for mortality; PTCA was associated with a decreased risk (HR 0.77, 95% CI: 0.66–0.91). Conclusion ESRD dialysis patients had a high incidence of ACS and mortality. Being male, elderly and having baseline comorbidities were independent risk factors for ACS. Coronary intervention is the possible benefits for dialysis patients.