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Diabetic kidney disease (DKD) is a critical microvascular complication of diabetes. With the continuous increase in the prevalence of diabetes since 2000, the prevalence of DKD has also been increasing in past years. The prevalence of DKD among individuals with type 2 diabetes in Taiwan increased from 13.32% in 2000 to 17.92% in 2014. The cumulative incidence of DKD among individuals with type 1 diabetes in Taiwan was higher than 30% during 1999–2012. DKD is the leading cause of end‐stage renal disease (ESRD), with a prevalence of approximately 45% in a population on chronic dialysis in Taiwan. Among individuals with type 2 diabetes, the prevalence of ESRD in the receipt of dialysis also increased from 1.32% in 2005 to 1.47% in 2014. Risk factors for DKD development are age, race, family history, hyperglycemia, hypertension, dyslipidemia, dietary patterns, and lifestyles. Prognostic factors that aggravate DKD progression include age, family history, sex, glycemic control, blood pressure (BP), microvascular complications, and atherosclerosis. This review summarizes updated information on the onset and progression of DKD, particularly in the Taiwanese population. Translating these epidemiological features is essential to optimizing the kidney care and improving the prognosis of DKD in Asian populations., This review summarizes updated information on the onset and progression of DKD, particularly in Taiwan. Translating these epidemiological features is essential to optimizing kidney care and improving the prognosis of DKD in Asian populations.

Some studies showed patients with chronic urticaria have a higher rate of peptic ulcer disease (PUD). Whether PUD is a risk factor for chronic urticaria is unclear. The objective of this study was to evaluate the incidence of and risk factors for chronic urticaria in patients with PUD using the Taiwan National Health Insurance Research Database. We conducted a retrospective nationwide cohort study of the period 2000–2012 and involving 11,901 patients with PUD who underwent Helicobacter pylori (HP) therapy (PUD + HP group) and an equal number of matched patients without HP infection (PUD − HP group). Furthermore, we enrolled 23,802 patients without PUD for comparison (non-PUD group). The Cox proportional hazards regression model was used to analyze chronic urticaria risk after adjusting for potential confounding factors. The mean ages of the three groups were around 50 years. Approximately 42.6% were female. Chronic urticaria incidences in the PUD + HP and PUD − HP groups were both significantly higher than that in the non-PUD group. The hazard ratios of chronic urticaria in the PUD + HP group and the PUD − HP group were 1.34 (95% confidence interval 1.09–1.64) and 1.45 (95% confidence interval 1.19–1.79), respectively. The risk difference became significant 2 years after patients with PUD had the HP infection tests and persisted till the end of follow-up. The risk increase was significant in patients with PUD who were female or aged 40–64 years. There was no difference in the risk comparison between PUD + HP and PUD − HP groups. Peptic ulcer disease, independent of HP infection, is associated with an increased chronic urticaria risk. Patients with PUD who were female or aged 40–64 years are more likely to have chronic urticaria.

Hepatocellular carcinoma (HCC) is the most common cancer in end-stage renal disease (ESRD) patients in Taiwan. Whether statin therapy associated with the HCC risk in hyperlipidemic patients with chronic kidney disease (CKD) and ESRD is unclear. Using population-based insurance claim data from Taiwan, we identified from hyperlipidemic patients taking statins or not (677,364 versus 867,707) in 1999–2015. Among them, three pairs of propensity score matched statin and non-statin cohorts were established by renal function: 413,867 pairs with normal renal function (NRF), 46,851 pairs with CKD and 6372 pairs with ESRD. Incidence rates of HCC were compared, by the end of 2016, between statin and non-statin cohorts, between hydrophilic statins (HS) and lipophilic statins (LS) users, and between statin-ezetimibe combination therapy (SECT) and statin monotherapy (SM) users. The HCC incidence increased progressively from NRF to CKD and ESRD groups, was lower in the statin cohort than in the non-statin cohort, with the differences of incidence per 10,000 person-years increased from (7.77 vs. 21.4) in NRF group to (15.8 vs. 37.1) in CKD group to (19.1 vs. 47.8) in ESRD group. The incidence increased with age, but the Cox method estimated hazard ratios showed a greater statin effectiveness in older patients. Among statin users, the HCC incidence was lower in HS users than in LS users, and lower in SECT users than in SM users, but the difference was significant only in the NRF group. Hyperlipidemic patients with CKD and ESRD receiving statins are at reduced HCC risks; the treatment effectiveness is superior for HS users than for LS users, and for SECT users than for SM users, but not significant.

Window of implantation (WOI) genes have been comprehensively identified at the single cell level. DNA methylation changes in cervical secretions are associated with in vitro fertilization embryo transfer (IVF-ET) outcomes. Using a machine learning (ML) approach, we aimed to determine which methylation changes in WOI genes from cervical secretions best predict ongoing pregnancy during embryo transfer. A total of 2708 promoter probes were extracted from mid-secretory phase cervical secretion methylomic profiles for 158 WOI genes, and 152 differentially methylated probes (DMPs) were selected. Fifteen DMPs in 14 genes (BMP2, CTSA, DEFB1, GRN, MTF1, SERPINE1, SERPINE2, SFRP1, STAT3, TAGLN2, TCF4, THBS1, ZBTB20, ZNF292) were identified as the most relevant to ongoing pregnancy status. These 15 DMPs yielded accuracy rates of 83.53%, 85.26%, 85.78%, and 76.44%, and areas under the receiver operating characteristic curves (AUCs) of 0.90, 0.91, 0.89, and 0.86 for prediction by random forest (RF), naïve Bayes (NB), support vector machine (SVM), and k-nearest neighbors (KNN), respectively. SERPINE1, SERPINE2, and TAGLN2 maintained their methylation difference trends in an independent set of cervical secretion samples, resulting in accuracy rates of 71.46%, 80.06%, 80.72%, and 80.68%, and AUCs of 0.79, 0.84, 0.83, and 0.82 for prediction by RF, NB, SVM, and KNN, respectively. Our findings demonstrate that methylation changes in WOI genes detected noninvasively from cervical secretions are potential markers for predicting IVF-ET outcomes. Further studies of cervical secretion of DNA methylation markers may provide a novel approach for precision embryo transfer.

(1) Purpose: Undesirable health care outcomes could conceivably increase as a result of the entry of new, less experienced health care personnel into patient care during the month of July (the July effect) or as a result of the less balanced allocation of health care resources on weekends (the weekend effect). Whether these two effects were present in Taiwan’s National Health Insurance (NHI) system was investigated. (2) Methods: The current study data were acquired from the NHI Research Database. The research sample comprised ≥18-year-old patients diagnosed as having a stroke for the first time from 1 January 2006 to 30 September 2012. The mortality rate within 30 days after hospitalization and readmission rate within 14 days after hospital discharge were used as health care quality indicators, whereas health care utilization indicators were the total length and cost of initial hospitalization. (3) Results: The results revealed no sample-wide July effect with regard to the four indicators among patients with stroke. However, an unexpected July effect was present among in-patients in regional and public hospitals, in which the total lengths and costs of initial hospitalization for non-July admissions were higher than those for July admissions. Furthermore, the total hospitalization length for weekend admissions was 1.06–1.07 times higher than that for non-weekend admissions; the total hospitalization length for weekend admissions was also higher than that for weekday admissions during non-July months. Thus, weekend admission did not affect the health care quality of patients with stroke but extended their total hospitalization length. (4) Conclusions: Consistent with the NHI’s general effectiveness in ensuring fair, universally accessible, and high-quality health care services in Taiwan, the health care quality of patients examined in this study did not vary significantly overall between July and non-July months. However, a longer hospitalization length was observed for weekend admissions, possibly due to limitations in personnel and resource allocations during weekends. These results highlight the health care efficiency of hospitals during weekends as an area for further improvement.

BackgroundFew investigations have evaluated the influences on peripheral arterial disease (PAD) risk of statin treatment in hemodialysis (HD) subjects with hyperlipidemia (HL).MethodsFrom the National Health Insurance Research Dataset, we identified 3658 HD patients with statin therapy for HL as the statin cohort, and then selected, by 1:1 propensity score matching, 3658 HD patients with HL but without statin use as the nonstatin cohort in 2000–07. The cohorts were followed through until the end of 2011. We used Cox proportional hazards regression analysis to assess the hazard ratio (HR) of PAD development.ResultsThe average follow-up period was 4.18 years; the incident PAD risk was 1.35-fold greater in statin users than in nonusers (16.87 versus 12.46/1000 person-years), with an adjusted HR (aHR) of 1.34 for PAD [95% confidence interval (CI) 1.12–1.62]. The PAD risk increases were significant for patients receiving fluvastatin (aHR 1.88; 95% CI 1.12–3.14) and atorvastatin (aHR 1.60; 95% CI 1.24–2.08). The risk increased with higher annual average statin dosage (P for trend ConclusionsHD patients with HL on statin medication were at increased PAD risk, which increased with cumulative statin dosage. Thorough considerations are needed before prescribing statins to HD patients.

P-cresol (PC) shows toxic effects on a variety of cells such as renal proximal tubular cells, glomerular mesangial cells, vascular smooth muscle cells, vascular endothelial cells, cardiomyocytes, cardiac fibroblasts, monocytes, osteoblasts and osteoclasts. The molecular mechanism and role of PC in the progression of urothelial carcinoma have not been documented. To understand the impact of PC on bladder cancer progression, human bladder cancer TSGH8301 cells were treated PC with various concentration (25-100 μM). MTT assay revealed the toxicity of PC on TSGH8301 cells dose-dependently. MMP-2 and MMP-9 expressions of the PC-treated cells were enhanced by using gelatin zymography. The wound healing assay and transwell migration analysis were performed to assay the migratory and invasive effects of PC on TSGH8301 cell and the migrated cell numbers were markedly increased by PC treatment. Moreover, we further detected the expression of Ras, PI3K and Akt proteins that involved in the invasion/migration of the cancer. Inhibiting the Ras and mTOR signaling pathways by Y27632 or/and everolimus improved cancer cell progression induced by PC. This study may clarify the impact of PC on migration and invasion of carcinoma cells.

Objective Fractures are a common reason for hospital admissions. However, regional and short-term studies show a varying incidence rate (IR) of fractures, and most of the surveys were conducted from only a few medical centers. Therefore, this study aims to investigate the epidemiological data of fracture hospitalizations of middle-aged and elderly persons in Taiwan between 2000 and 2015. Materials and methods Data from fractures occurring between 2000 and 2015 were obtained from the National Health Insurance Research Database in Taiwan for this study. The IR of fracture admission in patients, aged 40 years or older at the time of admission and first-time diagnosed with a fracture following admission, was calculated. Results We found that the IR of the fracture hospitalizations declined considerably from 95.70 per 10,000 person-years in 2000, to 68.48 per 10,000 person-years in 2015. The three most common fracture hospitalizations accounting for more than 50% of all fractures were fractures of the femur/hip, radius or ulna, and vertebral column. The IR of fracture hospitalization increased with age and was found to be higher in women than in men. The most common cause of fracture hospitalization for men and patients under 65 years of age was traffic accidents. In contrast, falls were the most frequent causes of fracture hospitalization for women and patients over 65 years of age. Conclusion The present study furnishes an updated picture of the incidence of fracture hospitalization over a 16-year period among middle-aged and elderly persons in Taiwan.

Background: The field of physician health is gaining increasing attention; however, most research and interventions have concentrated on factors such as job stress, mental health, and substance abuse. The risks of major cancers in physicians remain unclear. We used a propensity score-matched analysis to investigate the risk of cancer in physicians relative to the general population who had no healthcare-related professional background. Methods: Data were obtained from the National Health Insurance system in Taiwan. The physician cohort contained 29,713 physicians, and each physician was propensity score-matched with a person from the general population. Results: The physicians demonstrated a 0.90-fold lower risk of all-cancers (95% confidence interval [CI] = 0.83 – 0.96) when compared with the general population. Female physicians had a higher risk of cancer than male physicians (adjusted hazard ratio [HR] = 1.59; 95% CI = 1.28 – 1.96). Physicians had higher risks of prostate (HR = 1.26; 95% CI = 1.00 – 1.59) and thyroid cancers (HR = 3.16; 95% CI = 1.69 – 5.90) when compared with the general population. Conclusion: Physicians have lower rates of overall cancer risk than the general population. Female physicians have higher cancer risks than male physicians. Male physicians have higher risks of thyroid and prostate cancer relative to the general population.

There was a reduction in the hospitalization rate for major osteoporotic fractures. As per our analysis, hospitalization for site-specific fractures showed a declining trend for hip and vertebral fractures for both the sexes. However, an increasing trend was noted in women regarding hospitalization for forearm fracture. Major osteoporotic fractures (MOFs) constitute a large proportion of the total expenditures for public healthcare. Knowing the secular trends of MOF will allow for more efficient use of healthcare resources, but such data are insufficient for the current population of Taiwan. Therefore, we investigated the epidemiological data of MOF hospitalization from adults 50 years of age or older in Taiwan during the period 2000–2015. The data analyzed were acquired from the Taiwan National Health Insurance Research Database (NHIRD) entries between 2000 and 2015. All study subjects were 50 years of age or older at the time of admission and diagnosed as having MOF. A general decline was observed in the incidence rate (IR) of MOF hospitalization for the whole population, from 74.52 per 10,000 person-years (PYs) in 2000 to 55.19 in 2015. Females aged ≥65 years had the highest rates of hospitalization for MOF among the subgroups analyzed. Apart from the wrist fracture hospitalization rates in both sexes, which remained steady, all other site-specific fracture hospitalization rates exponentially increased with age. Among men, the IRs of all MOF hospitalization were steady, except for a slight decrease in hip and vertebral fracture hospitalizations. In women, hip and vertebral fracture hospitalization rates gradually decreased, humerus and wrist fracture hospitalization remained steady, and forearm fracture hospitalization increased. Hospitalization rates of MOF decreased. The trend of site-specific fracture hospitalization analysis showed that hip and vertebral fractures decreased for both sexes. However, an increasing trend in forearm fracture hospitalization was noticed among females.

Background Patients with end-stage renal disease (ESRD) who received parathyroidectomy (PTX) had persistently reduced levels of parathyroid hormone. The study investigated the risk of acute coronary syndrome (ACS) in patients with ESRD who underwent PTX using a nationwide health insurance claims database. Methods Of all ESRD patients, we selected 1047 individuals who had undergone PTX between 2000 and 2008 as the PTX group and 4188 patients who did not undergo PTX (non-PTX group) matched by propensity score. Multivariable Cox proportional hazards regression analysis was conducted for assessing the excess ACS risk for the PTX group compared to the non-PTX group. Results The mean follow-up periods were 4.63 and 4.04 years for the PTX and non- PTX groups, respectively. A significant reduction in the risk of ACS (adjusted hazard ratio = 0.74, 95% confidence interval = 0.57-0.96) was observed for the ESRD patients after PTX. Conclusions PTX is associated with reduced risk of ACS in patients with ESRD.

Introduction Limited studies have evaluated risk of stroke associated with the use of NSAIDs in patients with end-stage kidney disease. We examined the adverse effects of selective and nonselective NSAID use on the risk of stroke in dialysis patients. Methods A case-crossover study was conducted using medical claims data from the National Health Insurance Research Database in Taiwan. We identified patients with ischemic and hemorrhagic stroke (defined as International Classification of Diseases, 9th revision, Clinical Modification codes 433, 434, and 436 for ischemic stroke and 430 and 431 for hemorrhagic stroke) from inpatient claims during the period from 2003 to 2012. Conditional logistic regression models with adjustment for potential confounders were used to determine the effects of NSAID use on stroke. Results A total of 1190 dialysis patients with stroke were identified from 2003 to 2012. The results indicate a 1.31-fold increased risk of stroke related to NSAID use during the 30 days prior to a stroke (AOR = 1.31; 95% CI: 1.03–1.66); likewise, an excessive risk of ischemic stroke was observed (AOR = 1.34; 95% CI: 1.02–1.77). When classifying NSAIDs into selective and nonselective groups, nonselective NSAID use was significantly associated with an increased risk of stroke (AOR = 1.27; 95% CI: 1.00–1.61). Discussion In summary, the results show supportive evidence that NSAID use increased the risk of stroke in dialysis patients, which suggests the importance of closely monitoring the transient effects of initial NSAID treatment to patients on dialysis.

Background Cardiovascular (CV) disease contributes to nearly half of the mortalities in patients with end-stage renal disease. Patients who received prehemodialysis arteriovenous access (pre-HD AVA) creation had divergent CV outcomes. Methods We conducted a population-based cohort study by recruiting incident patients receiving HD from 2001 to 2012 from the Taiwan National Health Insurance Research Database. Patients’ characteristics, comorbidities, and medicines were analyzed. The primary outcome of interest was major adverse cardiovascular events (MACEs), defined as hospitalization due to acute myocardial infarction, stroke, or congestive heart failure (CHF) occurring within the first year of HD. Secondary outcomes included MACE-related mortality and all-cause mortality in the same follow-up period. Results The patients in the pre-HD AVA group were younger, had a lower burden of underlying diseases, were more likely to use erythropoiesis-stimulating agents but less likely to use renin–angiotensin–aldosterone system blockers. The patients with pre-HD AVA creation had a marginally lower rate of MACEs but a significant 35% lower rate of CHF hospitalization than those without creation (adjusted hazard ratio (HR) 0.65, 95% confidence interval (CI) [0.48–0.88]). In addition, the pre-HD AVA group exhibited an insignificantly lower rate of MACE-related mortality but a significantly 52% lower rate of all-cause mortality than the non-pre-HD AVA group (adjusted HR 0.48, 95% CI [0.39–0.59]). Sensitivity analyses obtained consistent results. Conclusions Pre-HD AVA creation is associated with a lower rate of CHF hospitalization and overall death in the first year of dialysis.

Background Renal hyperparathyroidism is a common complication of chronic kidney disease (CKD) or end-stage renal disease (ESRD) characterized by elevated parathyroid hormone levels secondary to derangements in the homeostasis of calcium, phosphate, and vitamin D. Rapid correction of severe and prolonged hyperparathyroidism by surgical parathyroidectomy in long-term hemodialysis patients occasionally causes hungry bone syndrome. These patients then exhibit severe and long-lasting secondary or tertiary hyperparathyroidism with high bone turnover. Case presentation We report a case of recurrent tertiary hyperparathyroidism after total parathyroidectomy due to supernumerary parathyroid gland in a patient with long-term hemodialysis. Supplementation with intravenous calcium, oral calcium, and vitamin D immediately after patient surgery helps to prevent and treat hungry bone syndrome. Conclusions We should prompt a search for the supernumerary parathyroid glands in ESRD patients, who have recurrent or persistent hyperparathyroidism after total parathyroidectomy. ESRD patients are more likely to develop hungry bone syndrome after parathyroidectomy. Prevention and treatment of hungry bone syndrome may be required after ectopic parathyroidectomy in clinical practice.

Background In real-world practice settings, there is insufficient evidence on the efficacy of antiplatelet drugs, including clopidogrel, aspirin, and ticlopidine, in stroke prevention. Purpose To compare the efficacies between aspirin and clopidogrel and aspirin and ticlopidine in stroke prevention. Methods This population-based case-cohort study utilized the data obtained from a randomized sample of one million subjects in the Taiwan National Health Insurance Research Database. Patients who were hospitalized owing to the primary diagnosis of ischemic stroke from January 1, 2000 to December 31, 2010 and treated with aspirin, ticlopidine, or clopidogrel were included in the study. Propensity score matching with a 1:4 ratio was performed to compare aspirin with ticlopidine and clopidogrel. The criteria for inclusion were the use of one of the three antiplatelet drugs for more than 14 days within the first month after the stroke and then continued use of the antiplatelet drugs until the study endpoint of recurrent stroke. Results During the 3-year follow-up period, the recurrent stroke rates were 1.62% (42/2585), 1.48% (3/203), and 2.55% (8/314) in the aspirin, ticlopidine, and clopidogrel groups, respectively. Compared with the patients treated with aspirin, those treated with clopidogrel and ticlopidine showed competing risk-adjusted hazard ratios of recurrent stroke of 2.27 (1.02–5.07) and 0.62 (0.08–4.86), respectively. Conclusion Compared with the patients treated with aspirin, those treated with clopidogrel were at a higher risk of recurrent stroke. For stroke prevention, aspirin was superior to clopidogrel whereas ticlopidine was not inferior to aspirin.

Clear cell carcinoma of the ovary (ovarian clear cell carcinoma (OCCC)) is one epithelial ovarian carcinoma that is known to have a poor prognosis and a tendency for being refractory to treatment due to unclear pathogenesis. Published investigations of OCCC have mainly focused only on individual genes and lack of systematic integrated research to analyze the pathogenesis of OCCC in a genome-wide perspective. Thus, we conducted an integrated analysis using transcriptome datasets from a public domain database to determine genes that may be implicated in the pathogenesis involved in OCCC carcinogenesis. We used the data obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) DataSets. We found six interactive functional gene clusters in the pathogenesis network of OCCC, including ribosomal protein, eukaryotic translation initiation factors, lactate, prostaglandin, proteasome, and insulin-like growth factor. This finding from our integrated analysis affords us a global understanding of the interactive network of OCCC pathogenesis.

Background With advancement of hemodialysis (HD) technique, late fistula failure (LFF) remains a problem significantly affecting life quality of patients. We attempt to identify factors affecting LFF in patients on chronic HD in Taiwan from the National Health Insurance Research Database. Methods This case–control study enrolled patients over 18 years old and who received regular HD for more than 3 months. LFF was defined as the first fistula failure episode beyond 3 months of chronic HD. We analyzed characteristics, comorbidities and medicine and investigated the association factors of LFF by logistic regression model. A trend test was conducted for risk in different provider levels. Sensitivity tests were conducted to test consistency. Results Of 1558 patients recruited, 772 (49.6%) were identified as LFF cases and 786 were identified as controls. The data showed that patients with diabetes mellitus (DM) had 42% increased rate of LFF. Patients receiving more than 10 HD sessions per month had a 90% increased rate of LFF; patients receiving chronic HD in private clinics had a 49% reduction rate of LFF. There were no significant differences in age, dialysis frequency, and comorbidities among different provider levels. There was a significant trend of risk reduction of the event from medical centers, regional hospitals, district hospitals, to private clinics. The sensitivity tests revealed similar results. Conclusions The factors associated with LFF include DM and receiving more HD sessions; on the contrary, receiving HD in private clinics is associated with less risk of LFF. Electronic supplementary material The online version of this article (10.1186/s12882-018-1010-6) contains supplementary material, which is available to authorized users.

Objective To determine the clinical effectiveness of influenza vaccination in patients with rheumatoid arthritis (RA). Methods The present study was conducted by using the Taiwan National Health Insurance Research Database. In this retrospective nationwide study, we included 3748 RA patients who received influenza vaccinations in 2008, 2009 and 2010, and 3748 matched RA patients who did not receive influenza vaccinations. We followed the patients from 4 weeks after influenza vaccination to the end of the influenza season in each year. After adjustment for potential confounding factors, including disease-modifying anti-rheumatic drugs, we used the Cox proportional hazards regression model to analyze the clinical effectiveness of influenza vaccination. Results The influenza vaccination rate in RA patients was 14.8% in 2008, 19.8% in 2009 and 9.50% in 2010. Receiving influenza vaccine was associated with reduced risk of hospitalization for septicemia, bacteremia or viremia (hazards ratio [HR] = 0.65, 95% CI = 0.45-0.94), and lower risk of mortality (HR = 0.62, 95% CI = 0.39-0.97). The effectiveness was particularly significant in elderly patients. Conclusions RA patients receiving influenza vaccine have significantly lower morbidity and mortality, particularly in elderly patients. Further studies are needed to explore effective policies to increase the vaccination rate in elderly RA patients.

Table S1. Analysis of factors affecting late fistula failure in patients on chronic hemodialysis. (DOCX 17 kb)

Table S2. Characteristics of patients categorized by dialysis provider level without dialysis catheter indwelling. (DOCX 18 kb)

Polycystic ovary syndrome (PCOS) is a complex disorder; various features of this disorder may influence bone metabolism and skeletal mass. The contribution of PCOS to lower bone mineral density has been recognized. However, the impact of PCOS on the long-term risks for fractures remains inconclusive. The aim of this study was to determine the risk of overall fracture and fractures at different anatomic sites in patients with PCOS. Using a nationwide health insurance claims database, we included 11,106 subjects, aged 15–80 years, with newly diagnosed PCOS (ICD-9-CM: 254.4X) during 2000–2012. Patients with PCOS and respective age-matched (1:4) controls without PCOS were enrolled. The occurrence of fracture was monitored until the end of 2013. Cox regression and computed hazard ratios (HR) with 95% confidence intervals (95% CI) were used to determine the risk of PCOS among women with fractures. The PCOS and non-PCOS groups were comprised of 11,106 patients with PCOS and 44,424 participants without PCOS, respectively. Patients with PCOS had a higher incidence of any fractures compared with non-PCOS group (10.16 versus 8.07 per 1000 person-years) and a greater risk of any fractures [adjusted hazard ratio (aHR) = 1.23, 95% CI = 1.13–1.33], osteoporotic fractures (aHR = 1.33, 95% CI = 1.15–1.54), spine fractures (aHR = 1.36, 95% CI = 1.11–1.66) and forearm fractures (aHR = 1.39, 95% CI = 1.07–1.80), but the risk for femur or hip fracture, humerus, wrist and non-osteoporotic fractures were not increased. In conclusion, the PCOS group had a higher occurrence rate of fractures than the non-PCOS group. These results provide evidence for the adverse effects of PCOS on the risk of fractures.

No previous large-scale research has reported the association of chewing areca nut (AN) with proteinuria. The aim of this study was to investigate such an association in men over a 7-year study. In this cross-sectional research, we retrospectively reviewed the records of health check-ups in a community hospital setting from 2003 to 2009. Laboratory tests, medical histories, and the status of smoking cigarettes, drinking alcohol, and chewing AN were obtained for each participant. Proteinuria was defined as having +/– or heavier protein response (including +/– to 4+) in a urine test performed by an automated chemical analyzer. We compared characteristics in participants with and without proteinuria, and analyzed the adjusted risk for proteinuria with chewing AN in middle-aged men. We also compared the changes in adjusted risk for proteinuria under a stricter definition of proteinuria (≥ 1+ proteinuria). There were 11,991 men with a mean age of 58.94 ± 12.06 years. The prevalence of proteinuria in AN chewers was 13.7%, and 11.2% for non-chewers ( p = 0.005). Of the 1381 participants with proteinuria, the proportion chewing AN was 15.3%, and 12.6% for those without proteinuria ( p = 0.005). In the multivariate logistic regression analysis with three different levels of adjustment models, with adjustment factors for age, drinking, smoking, hypertension, diabetes, hyperlipidemia, body mass index, chronic kidney disease, anemia, liver dysfunction, and hyperuricemia, the odds ratios of proteinuria for chewing AN were 1.61, 1.55 and 1.40 (all p = 0.000). With the stricter definition of proteinuria, the odds ratios became weaker (1.40, 1.36 and 1.19; p = 0.009, 0.029 and 0.24). We concluded that chewing AN was independently associated with risk of proteinuria in middle-aged Chinese men.