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IntroductionThe utilization of frozen embryo transfer not only enhances reproductive outcomes by elevating the likelihood of live birth and clinical pregnancy but also improves safety by mitigating the risks associated with ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. There has been an increasing debate in recent years regarding the advisability of making elective frozen embryo transfer the standard practice. Our study aims to determine the optimal choice between fresh and frozen embryo transfer, as well as whether the transfer should occur at the cleavage or blastocyst stage.MethodIn this retrospective cohort study conducted in Taiwan, data from the national assisted reproductive technology (ART) database spanning from January 1st, 2013, to December 31st, 2017, were analyzed. The study included 51,762 eligible female participants who underwent ART and embryo transfer. Pregnancy outcomes, maternal complications, and singleton neonatal outcomes were evaluated using the National Health Insurance Database from January 1st, 2013, to December 31st, 2018. Cases were categorized into groups based on whether they underwent fresh or frozen embryo transfers, with further subdivision into cleavage stage and blastocyst stage transfers. Exposure variables encompassed clinical pregnancy rate, live birth rate, OHSS, pregnancy-induced hypertension, gestational diabetes mellitus (DM), placenta previa, placental abruption, preterm premature rupture of membranes (PPROM), gestational age, newborn body weight, and route of delivery.ResultsFrozen blastocyst transfers showed higher rates of clinical pregnancy (CPR) and live births (LBR) compared to fresh blastocyst transfers. Conversely, frozen cleavage stage transfers demonstrated lower rates of clinical pregnancy and live birth compared to fresh cleavage stage transfers. Frozen embryo transfers were associated with reduced risks of OHSS but were linked to a higher risk of pregnancy-induced hypertension compared to fresh embryo transfers. Additionally, frozen embryo transfers were associated with a higher incidence of large for gestational age infants and a lower incidence of small for gestational age infants.ConclusionThe freeze-all strategy may not be suitable for universal application. When embryos can develop to the blastocyst stage, FET is a favorable choice, but embryos can only develop to the cleavage stage, fresh embryo transfer becomes a more reasonable option.

Abstract Whether cervical spondylosis (CS) is a risk factor for sudden sensorineural hearing loss (SSNHL) remains unclear. This study used national population-based data to investigate the risk of SSNHL in patients with CS in Taiwan of different ages and sexes. This study used data covering 2 million people in Taiwan, which were obtained from the National Health Insurance Research Database. The data that support the findings of this study are available from National Health Insurance Research Database but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the corresponding authors upon reasonable request and with permission of National Health Insurance Research Database. This retrospective cohort study enrolled 91,587 patients with a newly diagnosed CS between January 2000 and December 2018. Case and control cohorts were matched 1:1 according to age, sex, and comorbidities. SSNHL incidence rate and risk were compared between the groups. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The mean follow-up period was 8.80 (SD = 4.12) and 8.24 (SD = 4.09) years in the CS and control cohorts, respectively. The incidence rate of SSNHL in the CS cohort (85.28 per 100 000 person-years) was 1.49-fold significantly higher than that in the non-CS cohort (57.13 per 100,000 person-years) (95% CI 1.32–1.68, P

Objective Patients with type 2 diabetes mellitus (T2DM) are often immunosuppressed and susceptible to infectious diseases. We investigated the mortality and related risk factors of active TB disease in patients with T2DM in Taiwan.Materials and Methods The data of 1258 patients diagnosed with both T2DM and active TB disease from January 1 to December 31, 2002 (T2DM–TB group) were retrieved from the Taiwan National Health Insurance Research Database. Patients in the T2DM–TB group were matched by age, sex, and comorbidities to a control group of 10,064 T2DM patients without TB disease (T2DM group). Patients were followed up since TB diagnosis until death or 31 December 2011. Cox proportional-hazards regression analysis was employed to compare the risk of death between the T2DM group and the T2DM–TB group.Results A total of 101,837 potentially eligible patients were included in the study. After 1:10 propensity score matching, 1,258 patients were classified in the T2DM-TB group and 10,064 patients in the T2DM group. After adjustment for age, sex and comorbidities, the T2DM–TB group showed a 2.16-fold higher mortality risk than the T2DM group (95% CI = 1.83–2.56, p

Abstract Most new cases and the highest mortality rates of breast cancer occur among middle-aged and old women. The recurrence rate of early-stage invasive ductal carcinoma (IDC) among women aged ≥ 50 years and receiving different treatments remains unclear. Therefore, this study was conducted to determine these rates. We used Surveillance, Epidemiology, and End Results (SEER) data for this nationwide population-based cohort study. All women aged ≥ 50 years and diagnosed with early-stage IDC between 2000 and 2015 were identified and divided into three treatment groups, namely, breast conservation therapy (BCT), mastectomy alone (MAS), and mastectomy with radiation therapy (MAS + RT). The recurrence rates of IDC among these groups were then compared. The BCT group had a lower short-term recurrence risk than the MAS and MAS + RT groups (hazard ratio [HR]: 1.00 vs. 2.90 [95% CI 1.36–2.66] vs. 2.07 [95% CI 0.97–4.44]); however, the BCT group also had a higher long-term recurrence risk than MAS and MAS + RT groups (HR 1.00 vs. 0.30 [95% CI 0.26–0.35] vs. 0.43 [95% CI 0.30–0.63]). The high long-term recurrence rate of the BCT group was especially prominent at the 10- and 15-year follow-ups. The results provide valuable evidence of the most reliable treatment strategy for this population. Further studies including more variables and validation in other countries are warranted to confirm our findings.

Abstract Background Studies have revealed that patients with chronic kidney disease (CKD) have dietary patterns different from those of the general population. However, no studies have compared the dietary patterns of between patients with early-stages (stages 1–3a) and late-stages (stages 3b–5) of CKD. Our objective was to investigate the associations between dietary patterns in early and late-stage CKD. Methods We analyzed 4480 participants with CKD at various stages based on the data recorded between 2007 and 2016 from the database of the American National Health and Nutrition Examination Survey. Results In total, 3683 and 797 participants had early and late-stage CKD, respectively. Through principal components analysis, the dietary intake dimension was reduced from 63 variables to 3 dietary patterns. We adopted logistic regression for analysis. The three dietary patterns are as follows: (1) saturated fatty acids and mono-unsaturated fatty acids (MUFA); (2) vitamins and minerals; and (3) cholesterols and polyunsaturated fatty acids (PUFA). These 3 patterns explained > 50% of dietary nutrient intake. Results indicated that among participants with dietary patterns 2 (vitamins and minerals) and 3 (cholesterols and PUFA), those with low intakes were more likely to have late-stage CKD. The odds ratios for patterns 2 and 3 were 1.74 (95% CI: 1.21–2.50) and 1.66 (95% CI: 1.13–2.43), respectively. Conclusions This study revealed that intakes of vitamins and minerals and cholesterols and PUFA were associated with the stages of CKD.

Abstract 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 male 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 age, hypertension, hyperlipidaemia, and diabetes mellitus, male KCN patients were 1.75 times (adjusted HR = 1.75, 95 % [CI] = 1.14–2.68, p

Abstract Background Exercise improves glycemic control and functional capacity in elderly people with diabetes; however, its effect on health-related quality of life (HRQoL) and medical resource use remains unclear. This study aims to clarify the effect of exercise. Methods Using the data from National Health and Nutrition Examination Survey between 2007 and 2016, we identified 1572 elderly people with diabetes for this cross-sectional population-based study. Demographic characteristics, health conditions, comorbidities, HRQoL, and medical resource were compared among four groups (no exercise, low-intensity exercise, moderate-intensity exercise, and high-intensity exercise). Results The mean age of all participants was between 71.5 and 73.3 years. Male participants with higher education performed more exercise than their counterparts. The moderate- and high-intensity groups reported better general health condition than the no exercise group. Depression and worse health were more common in the no exercise group. Participants in the moderate-intensity exercise group had lower risk for depression than those in the no exercise group (adjusted odds ratio: 0.13, 95% confidence interval: 0.02–0.92) after adjusting for demographic characteristics, health conditions, and comorbidities, whereas participants in the low- and high-intensity exercise did not have a lower risk. The no exercise group had the highest proportions of emergency, hospitalization, and total healthcare visits. Conclusions Exercise is associated with better HRQoL, and lack of exercise is associated with higher medical resource use in elderly people with diabetes. Encouraging exercise is recommended in this population.

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.

Abstract 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.

Background and objectives: Traditional Chinese medicines (TCMs) are widely prescribed to relieve ischemic heart disease (IHD); however, no cohort studies have been conducted on the use of TCMs for patients with IHD. The aim of the study was to analyze TCM prescription patterns for patients with IHD. Materials and Methods: The retrospective population-based study employed a randomly sampled cohort of 4317 subjects who visited TCM clinics. Data were obtained from the National Health Insurance Research Database (NHIRD) of Taiwan for the period covering 2000 to 2017. Data analysis focused on the top ten most commonly prescribed formulae and single TCMs. We also examined the most common two- and three-drug combinations of TCM in single prescriptions. Demographic characteristics included age and sex distributions. Analysis was performed on 22,441 prescriptions. Results: The majority of TCM patients were male (53.6%) and over 50 years of age (65.1%). Zhi-Gan-Cao-Tang (24.76%) was the most frequently prescribed formulae, and Danshen (28.89%) was the most frequently prescribed single TCM for the treatment of IHD. The most common two- and three-drug TCM combinations were Xue-Fu-Zhu-Yu-Tang and Danshen” (7.51%) and “Zhi-Gan-Cao-Tang, Yang-Xin-Tang, and Gua-Lou-Xie-Bai-Ban-Xia-Tang” (2.79%). Conclusions: Our results suggest that most of the frequently prescribed TCMs for IHD were Qi toning agents that deal with cardiovascular disease through the promotion of blood circulation. The widespread use of these drugs warrants large-scale, randomized clinical trials to investigate their effectiveness and safety.

Abstract 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.

Abstract 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.

Abstract 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 relationship between temperature variability and HbA1c has been reported in Caucasians, but not for Asians of Taiwanese origin. This study investigated the impact of temperature on HbA1c in various groups of Taiwanese with type 2 diabetes in Taiwan. Methods: For this longitudinal follow-up study which started in 2006, we recruited a total of 4399 patients with type 2 diabetes who had been regularly followed up at Chi Mei Medical Center and obtained local temperature data for 2006 to 2011 from Taiwan's Central Weather Bureau. We used a generalized estimated equation (GEE) to analyze the HbA1c level and its change over time with temperature and temperature changes, respectively. Results: We found a negative correlation between HbA1c and temperature (R = −0.475, p = 0.001). For every 1°C decrement in temperature, there was an increase in the risk of having a HbA1c level >7% [p 7% among those in the lowest quartile of temperatures than the highest quartile (p = 0.0038, adjusted OR: 1.13). Patients with diabetic patients were at higher risk of HbA1C > 7% in the winter and spring than those in the summer (adjusted OR: 1.13, p = 0.0027; adjusted OR: 1.14, p = 0.0022). After adjusting for various confounders, we found people who were younger than 65 years old, people who had diabetes for longer than 6 years, and people who had a body mass index (BMI)

High-density lipoprotein (HDL) plays a vital role in lipid metabolism and anti-inflammatory activities; a dysfunctional HDL impairs cholesterol efflux pathways. To understand HDL’s role in patients with Alzheimer’s disease (AD), we analyzed the chemical properties and function. HDL from AD patients (AD-HDL) was separated into five subfractions, H1–H5, using fast-protein liquid chromatography equipped with an anion-exchange column. Subfraction H5, defined as the most electronegative HDL, was increased 5.5-fold in AD-HDL (23.48 ± 17.83%) in comparison with the control HDL (4.24 ± 3.22%). By liquid chromatography mass spectrometry (LC/MSE), AD-HDL showed that the level of apolipoprotein (apo)CIII was elevated but sphingosine-1-phosphate (S1P)-associated apoM and anti-oxidative paraoxonase 1 (PON1) were reduced. AD-HDL showed a lower cholesterol efflux capacity that was associated with the post-translational oxidation of apoAI. Exposure of murine macrophage cell line, RAW 264.7, to AD-HDL induced a vibrant expression of ganglioside GM1 in colocalization with apoCIII on lipid rafts alongside a concomitant increase of tumor necrosis factor-α (TNF-α) detectable in the cultured medium. In conclusion, AD-HDL had a higher proportion of H5, an apoCIII-rich electronegative HDL subfraction. The associated increase in pro-inflammatory (apoCIII, TNF-α) components might favor Amyloid β assembly and neural inflammation. A compromised cholesterol efflux capacity of AD-HDL may also contribute to cognitive impairment.

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.

Objective: Our previous study described the increasing adoption of uterine-preserving procedures in the surgical approach for uterine prolapse. In this follow-up study, we further explored the reoperation rate and variables for the choice of surgeries after primary uterine prolapse surgery, based on the nationwide claim data in Taiwan. Materials and methods: The data of this study was obtained from the Inpatient Expenditures by Admission files of the National Health Insurance Research Database (NHIRD). Women who received primary and repeat surgeries, either hysteropexy or hysterectomy, were identified between 1997 and 2010; and followed up to 2010 or till the event of reoperation. We analyzed the variables including the primary surgical type, concomitant stress urinary incontinence (SUI) surgery, patient age, surgeon age, and hospital accreditation level. Results: Among the total 36,609 women, a higher reoperation rate was noted in the hysteropexy group (156/4095) (3.81%) than in the hysterectomy group (116/32,514) (0.36%); the adjusted odds ratio (OR) was 11.70 [95% confidence interval (CI): 8.86–15.43]. It was lower in patients with concomitant SUI surgery; older patients (aged ≥ 60 years and 40–69 years vs.

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.

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.

BACKGROUND:Patients with advanced diabetic kidney disease (DKD) behave differently to diabetic patients without kidney disease. We aimed to investigate the associations of hypoglycemia and outcomes after initiation of dialysis in patients with advanced DKD on dialysis. METHODS:Using National Health Insurance Research Database, 20,845 advanced DKD patients beginning long-term dialysis between 2002 and 2006 were enrolled. We investigated the incidence of severe hypoglycemia episodes before initiation of dialysis. Patients were followed from date of first dialysis to death, end of dialysis, or 2008. Main outcomes measured were all-cause mortality, myocardial infarction (MI), and subsequent severe hypoglycemic episodes after dialysis. RESULTS:19.18% patients had at least one hypoglycemia episode during 1-year period before initiation of dialysis. Advanced DKD patients with higher adapted Diabetes Complications Severity Index (aDCSI) scores were associated with more frequent hypoglycemia (P for trend < 0.001). Mortality and subsequent severe hypoglycemia after dialysis both increased with number of hypoglycemic episodes. Compared to those who had no hypoglycemic episodes, those who had one had a 15% higher risk of death and a 2.3-fold higher risk of subsequent severe hypoglycemia. Those with two or more episodes had a 19% higher risk of death and a 3.9-fold higher risk of subsequent severe hypoglycemia. However, previous severe hypoglycemia was not correlated with risk of MI after dialysis. CONCLUSIONS:The rate of severe hypoglycemia was high in advanced DKD patients. Patients with higher aDCSI scores tended to have more hypoglycemic episodes. Hypoglycemic episodes were associated with subsequent hypoglycemia and mortality after initiation of dialysis. We studied the associations and further study is needed to establish cause. In addition, more attention is needed for hypoglycemia prevention in advanced DKD patients, especially for those at risk patients.

Background Pulmonary hypertension (PH) is a rare but fatal condition. Large‐scale studies to examine the prognostic factors are lacking. In the present study, we aimed to investigate the factors associated with overall mortality in PH patients. Methods and Results Based on Taiwan's National Health Insurance Database, we identified 1092 newly identified PH patients between 1999 and 2011. These patients were matched with 8736 healthy subjects based on propensity score calculated with age, sex, and chronic cardiovascular risk factors. Overall mortality, death incidence rate ratio, and hazard ratio were calculated. Patients with PH had a higher mortality than controls (56.45 versus 18.51 per 1000 person‐years, P

Prior studies of upper gastrointestinal bleeding (UGIB) and acute myocardial infarction (AMI) are small, and long-term effects of UGIB on AMI have not been delineated. We investigated whether UGIB in patients diagnosed with coronary artery disease (CAD) increased their risk of subsequent AMI. This was a population-based, nested case-control study using Taiwan's National Health Insurance Research Database. After propensity-score matching for age, gender, comorbidities, CAD date, and follow-up duration, we identified 1,677 new-onset CAD patients with AMI (AMI[+]) between 2001 and 2006 as the case group and 10,062 new-onset CAD patients without (AMI[-]) as the control group. Conditional logistic regression was used to examine the association between UGIB and AMI. Compared with UGIB[-] patients, UGIB[+] patients had twice the risk for subsequent AMI (adjusted odds ratio [AOR] = 2.08; 95% confidence interval [CI], 1.72-2.50). In the subgroup analysis for gender and age, UGIB[+] women (AOR = 2.70; 95% CI, 2.03-3.57) and patients < 65 years old (AOR = 2.23; 95% CI, 1.56-3.18) had higher odds of an AMI. UGIB[+] AMI[+] patients used nonsignificantly less aspirin than did UGIB[-] AMI[+] patients (27.69% vs. 35.61%, respectively). UGIB increased the risk of subsequent AMI in CAD patients, especially in women and patients < 65. This suggests that physicians need to use earlier and more aggressive intervention to detect UGIB and prevent AMI in CAD patients.

Health care workers (HCWs) in Taiwan have heavy, stressful workloads, are on-call, and have rotating nightshifts, all of which might contribute to peptic ulcer disease (PUD). We wanted to evaluate the PUD risk in HCWs, which is not clear. Using Taiwan's National Health Insurance Research Database, we identified 50,226 physicians, 122,357 nurses, 20,677 pharmacists, and 25,059 other HCWs (dieticians, technicians, rehabilitation therapists, and social workers) as the study cohort, and randomly selected an identical number of non-HCW patients (i.e., general population) as the comparison cohort. Conditional logistical regression analysis was used to compare the PUD risk between them. Subgroup analysis for physician specialties was also done. Nurses and other HCWs had a significantly higher PUD risk than did the general population (odds ratio [OR]: 1.477; 95% confidence interval [CI]: 1.433-1.521 and OR: 1.328; 95% CI: 1.245-1.418, respectively); pharmacists had a lower risk (OR: 0.884; 95% CI: 0.828-0.945); physicians had a nonsignificantly different risk (OR: 1.029; 95% CI: 0.987-1.072). In the physician specialty subgroup analysis, internal medicine, surgery, Ob/Gyn, and family medicine specialists had a higher PUD risk than other physicians (OR: 1.579; 95% CI: 1.441-1.731, OR: 1.734; 95% CI: 1.565-1.922, OR: 1.336; 95% CI: 1.151-1.550, and OR: 1.615; 95% CI: 1.425-1.831, respectively). In contrast, emergency physicians had a lower risk (OR: 0.544; 95% CI: 0.359-0.822). Heavy workloads, long working hours, workplace stress, rotating nightshifts, and coping skills may explain our epidemiological findings of higher risks for PUD in some HCWs, which might help us improve our health policies for HCWs.

Primary Sjögren's syndrome (pSS) is associated with immunological dysfunctions--a well-known risk factor of shingles. This study aimed to examine the incidence and risk of shingles in adults with pSS and pharmacological treatments.This retrospective population-based cohort study was conducted using National Health Insurance claims data. Using propensity scores, 4,287 pSS adult patients and 25,722-matched cohorts by age, gender, selected comorbidities and Charlson comorbidity index scores were identified. Kaplan-Meier analysis and Cox regression were conducted to compare the differences in developing shingles. In pSS, oral and eye dryness are treated with substitute agents. Extraglandular features are often treated with pharmacological drugs including steroids and immunosuppressants. pSS patients were grouped as follows: no pharmacological drugs, steroids alone; immunosuppressants alone; combined therapies.During the follow-up, 463 adults with pSS (10.80%) and 1,345 control cohorts (5.23%) developed shingles. The cumulative incidence of shingles in pSS patients (18.74/1,000 patient-years) was significantly higher than controls (8.55/1,000 patient-years). The adjusted hazard ratio (HR) of shingles was 1.69 (95% confidence interval (CI) 1.50-1.90). In age-subgroup analyses, incidences of shingles in pSS increased with age and peaked in pSS patients aged ≧60; however, adjusted HRs decreased with age. Compared to control cohorts with no drugs, adjusted HRs for shingles in pSS patients were ranked from high to low as: combined therapies (4.14; 95% CI 3.14-5.45) > immunosuppressants alone (3.24; 95% CI 2.36-4.45) > steroids alone (2.54; 95% CI 2.16-2.97) > no pharmacological drugs (2.06; 95% CI 1.76-2.41). Rates of shingles-associated hospitalization and postherpetic neuralgia were 5.62% and 24.41%, both of which were significantly higher than those (2.60%; 13.01%) in the control cohorts.Adults with pSS were at greater risk for shingles than control cohorts. Drug exposures significantly increased the risk of shingles in pSS.

ObjectivesWe used insurance claims of a nationally representative population-based cohort to assess the longitudinal treated prevalence and incidence of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents and adults.MethodsParticipants were identified from among National Health Insurance enrollees in Taiwan from 1999 to 2005. We identified study subjects who had at least one service claim during these years with a principal diagnosis of ADHD. A total of 6,173 patients were recorded in the treated ADHD cohort during the 6-year study.ResultsThere was a significant increase in the treated prevalence rate of ADHD during the study period, from 64.65 per 100,000 in 2000 to 145.40 per 100,000 in 2005 (p = .001). An increase in the treated incidence rate of ADHD, from 44.67 per 100,000 in 2000 to 81.20 per 100,000 in 2005, was also observed (p = .013). However, the treated prevalence of ADHD was still lower than that of the community data in Taiwan. The peak treated prevalence of ADHD was at age 7-12 years for both males and females, and the peak treated incidence of ADHD was at age 0-6 for females and age 7-12 for males. Overall, the treated incidence and prevalence rates dropped abruptly after age 13-18 (both pConclusionAlthough an increasing number of people with ADHD sought treatment during 1999-2005 in Taiwan, the treated prevalence of ADHD was still lower than that of the community data. The treated incidence and prevalence of ADHD fell dramatically after age 13-18. However, more women than men sought treatment in adulthood. There may be under-diagnosis and under-treatment of ADHD, especially among females and adults.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with systemic inflammation and induces various comorbid medical diseases. To date, no study has explored the relationship between OSA and atopic dermatitis (AD), an inflammatory and autoimmune skin disorder. This study investigated the longitudinal risk for AD in patients with OSA. METHODS: A random sample of 1,000,000 individuals from Taiwan's National Health Insurance database was collected. From this sample, 1222 patients with newly-diagnosed OSA between 2000 and 2005 were identified and compared with a matched cohort of 18330 patients without OSA. All patients were tracked for 5.5 years from the index date in order to identify which patients subsequently developed AD. RESULTS: During the 5.5-year follow-up period, the incidence rates of AD in the OSA cohort and comparison groups were 9.81 and 6.21 per 1000 person-years, respectively. After adjustment for age, gender, diabetes, hypertension, coronary heart disease, obesity, allergy, allergic rhinitis, asthma, monthly income, and geographic location, patients with OSA were 1.5-times more likely to develop AD than patients without OSA (95% CI = 1.15-1.95, p = 0.0025). The hazard risk for AD was greater in male OSA patients and young OSA patients (0-18 and 19-34 years), adjusted HRs being 1.53 (95% CI = 1.14-2.06, p = 0.005), 4.01(95% CI = 1.57-10.26, p = 0.0038) and 1.75(95% CI = 1.00-3.04, p = 0.0483), respectively. The log-rank test indicated that OSA patients

BACKGROUND: Carbon monoxide poisoning (COP) often produces severe complications and can be fatal. Because this topic has not been well delineated, we investigated long-term prognoses of patients with COP (COP[+]). METHODS: In this retrospective nationwide cohort study, 441 COP[+] patients and 8820 COP[-] controls (120) from 1999 to 2010 were selected from Taiwan's National Health Insurance Research Database. RESULTS: Thirty-seven (8.39%) COP[+] patients and 142 (1.61%) controls died (P

BACKGROUND: Previous studies have suggested that erectile dysfunction (ED) is an independent risk factor for macrovascular disease. Very few studies have evaluated the relationship between ED and risk of end stage renal disease (ESRD) requiring dialysis. METHODS: A random sample of 1,000,000 individuals from Taiwan's National Health Insurance database was collected. We selected the control group by matching the subjects and controls by age, diabetes, hypertension, coronary heart disease, hyperlipidemia, area of residence, monthly income and index date. We identified 3985 patients with newly-diagnosed ED between 2000 and 2008 and compared them with a matched cohort of 23910 patients without ED. All patients were tracked from the index date to identify which patients subsequently developed a need for dialysis. RESULTS: The incidence rates of dialysis in the ED cohort and comparison groups were 10.85 and 9.06 per 10000 person-years, respectively. Stratified by age, the incidence rate ratio for dialysis was greater in ED patients aged

BackgroundThe worldwide elderly (≥ 65 years old) dialysis population has grown significantly. This population is expected to have more comorbid conditions and shorter life expectancies than the general elderly population. Predicting outcomes for this population is important for decision-making. Recently, a new comorbidity index (nCI) with good predictive value for patient outcomes was developed and validated in chronic dialysis patients regardless of age. Our study examined the nCI outcome predictability in elderly dialysis patients.Methods and findingsFor this population-based cohort study, we used Taiwan's National Health Insurance Research Database of enrolled elderly patients, who began maintenance dialysis between January 1999 and December 2005. A total of 21,043 incident dialysis patients were divided into 4 groups by nCI score (intervals ≤ 3, 4-6, 7-9, ≥ 10) and followed nearly for 10 years. All-cause mortality and life expectancy were analyzed. During the follow-up period, 11272 (53.55%) patients died. Kaplan-Meier curves showed significant group difference in survival (log-rank: PConclusionThe nCI, even without the age component, is a strong predictor of mortality in elderly dialysis patients. Because patients with lower nCI scores may predict better survival, more attention should paid to adequate dialysis rather than palliative care, especially in those without obvious functional impairments.

INTRODUCTION: Lower urinary tract symptoms (LUTS), which encompass storage, voiding, and postmicturition symptoms, are highly prevalent and recognized globally. Based on a nationwide population-based database, this study tests the hypothesis that medical attendance for LUTS is associated with a subsequent increase in the number of outpatient visits and hospitalizations, with differences among medical specialties and age groups. METHODS: Participants were selected from a random population sample of approximately one million people as a representative cohort of National Health Insurance (NHI) enrollees in Taiwan. Participants had at least three outpatient service claims with a coding of LUTS during the recruitment period 2001-2004. Both the LUTS group and non-LUTS control group were monitored for subsequent outpatient visits and hospitalizations, excluding LUTS-related healthcare services, for 2 years following the index date. The results were categorized based on medical specialty and age group. RESULTS: The outpatient visit rates (no. per person-year) and adjusted incidence rate ratios (IRRs) (95% confidence interval (CI) were significantly higher in urology (4.51, 95%CI 4.15-4.91) and gynecology (1.82, 95%CI 1.76-1.89) for the LUTS group. They were also significantly high in other departments, including internal medicine (1.25), general practice (1.13), Chinese medicine (1.77), family medicine (1.19), surgery (1.38), and psychiatry (1.98). Similarly, the hospitalization rate (no. per 1000 person-year) and adjusted IRRs (95% CI) were significantly higher in urology (5.50, 95% CI = 4.60-6.50) and gynecology (1.60, 95% CI = 1.35-1.90), as well as in internal medicine (1.55) and surgery (1.56), but not in psychiatry (1.12). Furthermore, the IRRs differed among 3 age groups. CONCLUSIONS: A significantly higher number of outpatient visits and hospitalizations were observed for individuals with LUTS, compared to the control group, and the effects differed with the advancement of age. This study broadens understanding of LUTS by viewing their impact on healthcare services with multiple and overlapping systems, rather than considering them exclusively as symptoms of traditional diseases of the bladder and urethra.

Lower urinary tract symptoms (LUTS) have been reported to be associated with metabolic syndrome and may predispose subjects to cardiovascular disease. The magnitude of the impact on the medical care remains to be elucidated. Based on a population-based claims dataset in Taiwan, we explored the association between LUTS and the risk of subsequent hospitalization for acute cardiovascular events.Among a representative sample of one million subjects from nationwide health insurance enrollees, subjects with codes of LUTS in service claims and without previous cardiovascular diseases including stroke were compared with age- and sex-matched non-LUTS subjects in subsequent hospitalization for acute coronary syndrome or stroke from the recruited date (between 2001-2004) to 2009. The risk of outcomes was assessed with Kaplan-Meier curves and the impact of LUTS was estimated with Poison regression analysis and Cox proportional hazards models.We included 4,553 LUTS subjects and 22,765 matched non-LUTS subjects, with a mean age of 47 years and 43% of men. Hypertension, diabetes, and hyperlipidemia were more prevalent in the LUTS group. The incidence rate of the composite endpoint was significantly higher in the LUTS group than in the non-LUTS group (5.4/1000 vs. 4.0/1000 person-years). The difference mainly derived from stroke rather than acute coronary syndrome. After adjusting for age, sex, diabetes, hypertension, and hyperlipidemia in multivariable analysis, LUTS remained a significant predictor (hazard ratio, 1.29; 95% confidence incidence, 1.06-1.50).Subjects free of cardiovascular disease and presenting with LUTS are at risk of subsequent hospitalization for acute cardiovascular events, mainly stroke. The information might prompt practitioners encountering such patients to undergo appropriate diagnostic and preventive measures.

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 < 0.001). The same result was found for ovarian cancer incidence per 1000 person- years. Conclusion: Our data show that pelvic inflammatory disease is associated with cancer development in women with pre-existing endometriosis. [ABSTRACT FROM AUTHOR]