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BackgroundChronic kidney disease (CKD) is known to increase the risk of atrial fibrillation (AF) development, but the relationship between AF and subsequent renal function decline in patients with CKD is not well understood. In this study, we explored the role of AF on renal outcomes among patients with CKD.MethodsIn a retrospective hospital-based cohort study, we identified patients with CKD aged ≥20 years from 1 January 2008 to 31 December 2018. The patients were divided into AF and non-AF groups. We matched each patient with CKD and AF to two non-AF CKD controls according to propensity scores. The outcomes of interest included estimated glomerular filtration rate (eGFR) decline of ≥20%, ≥30%, ≥40% and ≥50%, and end-stage renal disease (ESRD).ResultsAfter propensity score matching, 6731 patients with AF and 13 462 matched controls were included in the analyses. Compared with the non-AF group, the AF group exhibited greater risks of eGFR decline ≥20% (HR 1.43; 95% CI 1.33 to 1.53), ≥30% (HR 1.50; 95% CI 1.36 to 1.66), ≥40% (HR 1.62; 95% CI 1.41 to 1.85) and ≥50% (HR 1.82; 95% CI 1.50 to 2.20), and ESRD (HR 1.22; 95% CI 1.12 to 1.34). Higher CHA2DS2-VASc scores were associated with greater risks of eGFR decline and ESRD.ConclusionsIn patients with CKD, AF was associated with greater risks of subsequent renal function decline. CHA2DS2-VASc scores may be a useful risk stratification scheme for predicting the risk of renal function decline.

Influenza vaccine effectively reduced risks for in-hospital death or hospitalization, regardless of statin use., Debates on whether statin use reduces the effectiveness of influenza vaccines against critical illness and death among persons >65 years of age continue. We conducted a study of 9,427,392 persons >65 years of age who did and did not receive influenza vaccinations during 12 consecutive influenza seasons, 2000–01 through 2011–12. Using data from Taiwan’s National Health Insurance Research Database, we performed propensity score-matching to compare vaccinated persons with unvaccinated controls. After propensity score-matching, the vaccinated group had lower risks for in-hospital death from influenza and pneumonia and for hospitalization for pneumonia and influenza, circulatory conditions, and critical illnesses compared with the unvaccinated group. We stratified the 2 groups by statin use and analyzed data by interaction analysis and saw no statistically significant difference. We found that influenza vaccine effectively reduced risks for hospitalization and death in persons >65 years of age, regardless of statin use.

Vascular diseases are commonly observed in patients with autosomal dominant polycystic kidney disease (ADPKD). We aim to investigate the differences in the risk for arteriovenous fistula or graft (AVF/AVG) dysfunction in haemodialysis (HD) patients with and without ADPKD. 557 ADPKD and 1671 non-ADPKD patients were enrolled in the study after propensity score matching. The primary outcome measure is the incidence rate of AVF/AVG dysfunction. The incidence rates and risks of AVF/AVG dysfunction (per 100 person-years) for ADPKD and non-ADPKD patients were (1) 38.83 and 48.99 [SHR = 0.79, P = 0.137], respectively, for within 90 days, (2) 45.85 and 51.31 [SHR = 0.90, P = 0.300], respectively, for within 180 days, (3) 44.42 and 41.40 [SHR = 1.08, P = 0.361], respectively, for within the first year, (4) 27.38 and 24.69 [SHR = 1.09, P = 0.168], respectively, for within 5 years, (5) 17.35 and 13.80 [SHR = 1.19, P = 0.045], respectively, for between the 1st and 10th year, and (6) 25.40 and 21.22 [SHR = 1.14, P = 0.031], respectively, for all periods. ADPKD patients had lower incidence rates of AVF/AVG dysfunction within the first 180 days than non-ADPKD patients, but presented a higher incidence rate after 1 year of AVF/AVG creation and onwards.

Background: Galectin-3 (Gal-3) is a multifunctional glycan-binding protein shown to be linked to chronic inflammation and fibrogenesis. Plasma Gal-3 is associated with proteinuria and renal dysfunction, but its role has never been confirmed with kidney biopsy results. In our study, we aimed to explore the expression of Gal-3 in biopsy-proven patients, and we tested the hypothesis that chronic kidney disease (CKD) leads to upregulation of plasma Gal-3 expression in corresponding biopsy findings and RNA sequencing analysis.Method: In 249 patients (male/female: 155/94, age: 57.2 ± 16.3 years) who underwent kidney biopsy, plasma levels of Gal-3 were measured to estimate the association of renal fibrosis. Relationships between plasma Gal-3 levels, estimated glomerular filtration rate (eGFR) and renal histology findings were also assessed. We further examined the gene expression of Gal-3 in RNA-sequencing analysis in biopsy-proven patients.Results: Compared to patients without CKD, CKD patients had higher levels of plasma Gal-3 (1,016.3 ± 628.1 pg/mL vs. 811.6 ± 369.6 pg/ml; P = 0.010). Plasma Gal-3 was inversely correlated with eGFR (P = 0.005) but not with proteinuria. Higher Gal-3 levels were associated with interstitial fibrosis, tubular atrophy and vascular intimal fibrosis. RNA-sequencing analysis showed the upregulation of Gal-3 in fibrotic kidney biopsy samples, and the differentially expressed genes were mainly enhanced in immune cell activation and the regulation of cell-cell adhesion.Conclusions: Plasma Gal-3 levels are inverse correlated with eGFR but positively correlated with renal fibrosis, which may be involved in the immune response and associated pathways. These findings support the role of Gal-3 as a predictive marker of renal fibrosis.

Polyacrylonitrile (AN69) filter membranes adsorb cytokines during continuous venovenous hemofiltration (CVVH). Although high-volume hemofiltration has shown limited benefits, the dose-effect relationship in CVVH with AN69 membranes on severe sepsis remains undetermined. This multi-centered study enrolled 266 patients with sepsis-induced multiorgan dysfunction syndrome (MODS) who underwent CVVH with AN69 membranes between 2014 and 2015. We investigated the effects of ultrafiltration rates (UFR) on mortality. We categorized patients that were treated with UFR of 20–25 mL/kg/h as the standard UFR group (n = 124) and those that were treated with a UFR &gt, 25 mL/kg/h as the high UFR group (n = 142). Among the patient characteristics, the baseline estimated glomerular filtration rates (eGFR) &lt, 60 mL/min/1.73 m2, hemoglobin levels &lt, 10 g/dL, and a sequential organ failure assessment (SOFA) score ≥15 at CVVH initiation were independently associated with in-hospital mortality. In the subgroup analysis, for patients with SOFA scores that were ≥15, the 90-day survival rate was higher in the high UFR group than in the standard UFR group (HR 0.54, CI: 0.36–0.79, p = 0.005). We concluded that in patients with sepsis-induced MODS, SOFA scores ≥15 predicted a poor rate of survival. High UFR setting &gt, 25 mL/kg/h in CVVH with AN69 membranes may reduce the mortality risk in these high-risk patients.

Background: Oral anticoagulants (OAC) plus antiplatelets is recommended for patients with atrial fibrillation (AF) and coronary artery disease (CAD) to reduce thromboembolism. However, there is limited evidence regarding antithrombotic therapy for patients with concomitant chronic kidney disease (CKD), AF, and CAD, especially those not undergoing percutaneous coronary intervention. We aimed to use real-world data assessing the efficacy and safety of antithrombotic regimens in this population.Methods: We used a single-center database of 142,624 CKD patients to identify those receiving antithrombotic therapy for AF and CAD between 2010 and 2018. Patients taking warfarin or direct OAC (DOAC) alone were grouped in the OAC monotherapy (n = 537), whereas those taking OAC plus antiplatelets were grouped in the combination therapy (n = 2,391). We conducted propensity score matching to balance baseline covariates. The endpoints were all-cause mortality, major adverse cardiovascular events, and major bleedings.Results: After 1:4 matching, the number of patients in OAC monotherapy and combination therapy were 413 and 1,652, respectively. Between the two groups, combination therapy was associated with higher risks for ischemic stroke (HR 2.37, CI 1.72–3.27), acute myocardial infarction (HR 6.14, CI 2.51–15.0), and hemorrhagic stroke (HR 3.57, CI 1.35–9.81). The results were consistent across CKD stages. In monotherapy, DOAC users were associated with lower risks for all-cause mortality, AMI, and gastrointestinal bleeding than warfarin, but the stroke risk was similar between the two subgroups.Conclusions: For patients with concomitant CKD, AF and CAD not undergoing PCI, OAC monotherapy may reduce stroke and AMI risks. DOAC showed more favorable outcomes than warfarin.

Galectin-3 reportedly participates in the inflammatory process that causes insulin resistance in the target tissues. However, the role of high plasma galectin-3 levels as an indicator of protein-energy wasting (PEW) in patients undergoing maintenance hemodialysis remains unclear. This study included 240 hemodialysis patients (64.5 [55.3−74.0] years, 35.8% women) from a tertiary medical center. A baseline assessment of demographic and clinical data, biochemical parameters, and body composition was conducted. Plasma galectin-3 and other biomarkers were measured using a multiplex bead-based immunoassay. Participants were then divided into two subgroups depending on the median value of plasma galectin-3. Malnutrition was identified using the geriatric nutritional risk index (GNRI) and the criteria of the International Society of Renal Nutrition and Metabolism. Independent risk factors for elevated plasma galectin-3 and malnutrition were identified by multivariate logistic regression. The high galectin-3 group was more likely to be older, have lower lean tissue mass and GNRI scores, be diagnosed with PEW, dialyze through a tunneled catheter, and have higher circulating IL-6, TNF-α, and MCP-1 concentrations than the low galectin-3 group. After multivariate adjustment, only low mean arterial pressure, dialyzing with tunneled cuffed catheters, and elevated systemic inflammatory markers correlated with high galectin-3 levels. Plasma galectin-3 concentrations also increased significantly in hemodialysis patients with PEW. However, compared with other commonly used nutritional indicators, galectin-3 did not show superiority in predicting PEW. Although the plasma galectin-3 levels correlated with PEW severity, this correlation disappeared after adjustment for potential confounding variables (OR, 1.000, 95% CI, 0.999–1.001). In conclusion, plasma galectin-3 is a valuable biomarker for systemic inflammation but is less prominent for PEW in patients with maintenance hemodialysis. Further identification of novel biomarkers is required to detect patients at risk for malnutrition and implement appropriate interventions.

Protein-energy wasting (PEW) is associated with adverse outcomes in hemodialysis patients. This study compares the simplified creatinine index (SCI) and circulating inflammatory markers as nutritional screening tools for hemodialysis patients. Maintenance hemodialysis patients (230 total patients, 34.8% women, 64.0 ± 14.3 years old) from a tertiary medical center were assessed for demographic data, body composition analysis, biochemistry tests, and circulating inflammatory biomarkers. The SCI was calculated using Canaud’s formula. Reduced fat-free mass index (FFMI), a surrogate of lean body mass, was identified according to the European Society for Clinical Nutrition and Metabolism guidelines. Nutritional status was assessed by the geriatric nutritional risk index (GNRI) and International Society of Renal Nutrition and Metabolism (ISRNM) criteria. Multivariate logistic regression revealed independent risk factors for low FFMI and malnutrition. Of the patients, 47.4% had low FFMI. Patients with a reduction in FFMI tended to be older females with lower body mass index, SCI, and GNRI scores but significantly higher levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-8. SCI was found to be an independent predictor for reduced FFMI (OR 0.57, 95% CI 0.40–0.81) and presence of PEW according to ISRNM criteria (OR 0.38, 95% CI 0.21–0.68). Although a positive association between systemic inflammatory markers and low FFMI was observed, this association disappeared in multivariate analysis. Moreover, the inflammatory markers examined in this study were not associated with malnutrition after adjusting for potential confounders. Compared with markers of systemic inflammation, SCI achieved better performance in assessing the nutritional status of hemodialysis patients.

Patients with systemic lupus erythematosus (SLE) have a higher risk of vascular complications. This retrospective cohort study aimed to analyze the differences in the risk of arteriovenous fistula or graft (AVF/AVG) dysfunction in hemodialysis patients with and without SLE from Taiwan’s National Health Insurance Database over a 10-year period. AVF/AVG dysfunction is defined as the occurrence of the first episode of intervention after vascular access creation. A total of 1366 HD patients with SLE had higher incidence rates of AVF/AVG dysfunction than 4098 non-SLE HD patients in the following 4 periods: (1) after 1 year (incidence rates = 15.21% and 13.01%, respectively; subdistribution hazard ratio (SHR) = 1.16; P = 0.007), (2) 1st-to-10th-year period (15.36% and 13.25%; SHR = 1.16; P = 0.007), (3) 5th-to-10th-year period (11.91% and 8.1%; SHR = 1.42; P = 0.003), and (4) overall period (23.53% and 21.66%; SHR = 1.09; P = 0.027). In conclusion, there were significantly higher incidence rates of AVF/AVG dysfunction in SLE patients during the long-term follow-up period. Vascular access function should be monitored regularly by clinical examinations, especially after 1 year and during 5 to 10 years, to improve AVF/AVG patency and dialysis adequacy in SLE patients undergoing maintenance hemodialysis.

Objective The objective of this study is to determine whether vaccination against influenza is associated with a reduced risk of acute kidney injury (AKI) in a nationwide cohort of adults aged ≥65 years. Methods We investigated a total of 13,270 patients aged ≥65 years who were hospitalized for AKI between 2000 and 2013 from Taiwan's National Health Insurance Research Database. Each AKI case was matched with one control subject according to duration of follow-up, age, sex, monthly income, urbanization level, and baseline comorbidities. Odds ratios (ORs) for AKI associated with exposure to the influenza vaccine in the previous year were calculated in a nested case-control analysis. Results Influenza vaccination in the previous year was associated with a lower risk of AKI (adjusted OR 0.67, 95% confidence interval [CI] 0.63–0.72). Compared with a reference group of unvaccinated individuals with no influenza infection, vaccination with no influenza infection was associated with a lower risk of AKI (adjusted OR 0.68, 95% CI 0.64–0.73). Lack of vaccination and presence of influenza infection was associated with a higher risk of AKI (adjusted OR 1.78, 95% CI 1.57–2.01), whereas the risk of AKI was insignificant in vaccinated patients who developed influenza (adjusted OR 1.01, 95% CI 0.69–1.18). Conclusions The risk of AKI was 37% lower among older people who received vaccination against influenza in a real-world setting. Further work is required to clarify causality.

Nephrotic syndrome is a well-known risk factor of deep vein thrombosis (DVT). Catheter-related DVT under the setting of nephrotic syndrome may be presented as a more fulminant form, phlegmasia cerulea dolens. Phlegmasia cerulea dolens may lead to severe obstruction of venous drainage of the extremities and presents with compartment syndrome that impairs arterial perfusion. Aggressive management with thrombolysis and/or thrombectomy are considered with simultaneous anticoagulant treatment.

High serum lipid levels are independent predictors of mortality risk in the general population. Recent data suggest that this may not apply in the older populations, and even acts in the opposite direction. In consideration of the frail state, minimum amount of physical activity (60–100 minutes each week) may be more suitable for older individuals but its role in lipid profiles has never been explored. Between 2006 and 2010, we conducted a cohort study of 83,820 participants aged ≥65 years using the Taipei City Elderly Health Examination Database. Participants were classified as inactive, low or high in their level of physical activity. Older individuals with lowest quintile of total cholesterol, non-HDL and HDL were associated with increased risk of all-cause mortality compared to those with other quintile of these lipid profiles. Compared to inactive older individuals, both low (adjusted hazard ratios [aHR] 0.75, 95% confidence interval [CI] 0.70–0.81) and high active older individuals (aHR 0.55, 95% CI 0.51–0.59) were associated with lower risks of mortality. Physical activity, even minimum volume of exercise, in older people has to be encouraged to reduce the increased risk of mortality from low serum lipid levels.

We investigated the risk and impact of mycobacterium tuberculosis (TB) infection in patients with multiple myeloma (MM). We identified 3979 MM patients from Taiwan's National Health Insurance database between 2000 and 2011 and compared the incidence rates of TB infection in these patients with 15,916 randomly selected age-, sex-, and comorbidity-matched subjects without MM. The risk of TB was higher in the myeloma cohort (adjusted hazard ratio [HR] 3.11, 95% confidence interval [CI] 2.41-4.02). Risk factors for MM patients contracting TB were age ≥65 (adjusted HR 1.93, 95% CI 1.19-3.15), alcohol use disorder (adjusted HR 2.86, 95% CI 1.24-6.62), and steroid daily dose equivalent to prednisone 5 mg or more (adjusted HR 2.38, 95% CI 1.50-3.77). MM patients with TB had a higher mortality risk than those without (adjusted HR 2.03, 95% CI 1.54-2.67). The incidence of TB is significantly higher in MM patients.

Background Although theophylline has been shown to have anti-inflammatory effects, the therapeutic use of theophylline before sepsis is unknown. The aim of our study was to determine the effect of theophylline on COPD patients presenting with sepsis. Methods This nationwide, population-based, propensity score-matched analysis used data from the linked administrative databases of Taiwan's National Health Insurance program. Patients with COPD who were hospitalized for sepsis between 2000 and 2011 were divided into theophylline users and non-users. The primary outcome was 30-day mortality. The secondary outcome was in-hospital death, intensive care unit admission, and need for mechanical ventilation. Cox proportional hazard model and conditional logistic regression were used to calculate the risk between groups. Results A propensity score-matched cohort of 51,801 theophylline users and 51,801 non-users was included. Compared with non-users, the 30-day (HR 0.931, 95% CI 0.910–0.953), 180-day (HR 0.930, 95% CI 0.914–0.946), 365-day (HR 0.944, 95% CI 0.929–0.960) and overall mortality (HR 0.965, 95% CI 0.952–0.979) were all significantly lower in theophylline users. Additionally, the theophylline users also had lower risk of in-hospital death (OR 0.895, 95% CI 0.873–0.918) and need for mechanical ventilation (OR 0.972, 95% CI 0.949–0.997). Conclusions Theophylline use is associated with a lower risk of sepsis-related mortality in COPD patients. Pre-hospital theophylline use may be protective to COPD patients with sepsis.

Cytomegalovirus (CMV) infection is a common infectious complication in immunocompromised patients. The colon is the most common site of CMV infection in the gastrointestinal tract. Rarely, however, invasion of the upper gastrointestinal tract, such as the esophagus or stomach, has been reported. Herein, we describe the first reported case of CMV gastritis in a patient with end-stage renal disease and uremic symptoms (including nausea, vomiting, and poor appetite) who had begun hemodialysis therapy. This patient was not a transplant recipient and was not receiving immunosuppressant treatment. As CMV gastritis is easily over looked in patients with end-stage renal disease, physicians should maintain a high index of suspicion and establish the diagnosis as early as possible using an upper GI endoscopic biopsy and adequate staining.

Whether elevated serum uric acid levels (SUA) predict renal dysfunction remains controversial in the elderly. Therefore, we investigated the association between SUA and early renal function decline defined as an estimated glomerular filtration rate (eGFR) reduction ≥30% over 2 years. From 2001 to 2010, we conducted a longitudinal cohort study comprising 44,078 participants aged ≥65 years in the Taipei City Elderly Health Examination Database. Participants were classified by 1-mg/dL increment of SUA. We used multivariable logistic and Cox regression analyses to compare the risk of early renal function decline in different SUA groups. Compared to the reference SUA group of 5.0–5.9 mg/dL, hyperuricemic participants had increased risks of eGFR decline, starting at SUA ≥6.0 mg/dL (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] = 1.00–1.45). The risk progressively elevated as SUA increased, with the highest in the SUA ≥10.0 mg/dL group (aOR = 3.20, CI = 2.39–4.28). Multivariable Cox regression further confirmed that hyperuricemia was 1.12-fold (CI = 1.03–1.22, SUA ≥6.0 mg/dL) to 1.6-fold (CI = 1.37–1.86, SUA ≥10.0 mg/dL) more likely to develop early eGFR decline. Hyperuricemia-associated increased risks for early eGFR decline were consistent across subgroup and sensitivity analyses. Collectively, SUA ≥6.0 mg/dL independently predicted early renal dysfunction with eGFR decline ≥30% over 2 years in older people.

Background Although recent clinical trials raised concerns about the risk for heart failure (HF) in dipeptidyl peptidase-4 (DPP-4) inhibitor use, data on the cardiovascular risks in the patients with pre-existing HF are still lacking. Methods We used Taiwan9s National Health Insurance Research Database to identify 196 986 patients diagnosed with type 2 diabetes mellitus (T2DM) who had previous history of HF between 2009 and 2013. This population included 30 204 DPP-4 inhibitor users and 166 782 propensity score-matched DPP-4 inhibitor non-users. The outcomes of interest were all-cause mortality, combination of myocardial infarction (MI) and ischaemic stroke, and hospitalisation for HF. Results The incidence in DPP-4 users compared with non-users was 67.02 vs 102.85 per 1000 person-years for all-cause mortality, 37.89 vs 47.54 per 1000 person-years for the combination of MI and ischaemic stroke, 12.70 vs 16.18 per 1000 person-years for MI and 26.37 vs 32.46 per 1000 person-years for ischaemic stroke. The risk of all-cause mortality was lower in DPP-4 inhibitor users (HR 0.67, 95% CI 0.64 to 0.70), combination of MI and stroke (HR 0.81, 95% CI 0.76 to 0.87), MI (HR 0.80, 95% CI 0.71 to 0.89) and ischaemic stroke (HR 0.83, 95% CI 0.76 to 0.89) than in non-users. Notably, the risk of hospitalisation for HF did not differ significantly between groups. The results were similar after accounting for death as a competing risk. Conclusions In this nationwide T2DM cohort, the risks of mortality and the combination of MI and ischaemic stroke were lower for patients receiving DPP-4 inhibitors than for those who did not receive such treatment. DPP-4 inhibitor use was not associated with a higher risk of hospitalisation for HF even in patients with pre-existing HF.

Rationale: Patients with sepsis who survive to hospital discharge may present with ongoing high morbidity and mortality. However, little is known about the risk of long-term, all-cause mortality and cardiovascular outcomes after sepsis.Objectives: Our study aimed to investigate the long-term clinical outcomes in sepsis survivors.Methods: In this nationwide population-based study, data from patients with sepsis were retrieved from Taiwan’s National Health Insurance Research Database between 2000 and 2002. Each sepsis survivor was 1:1 propensity-matched to control subjects from two different control populations: subjects who were in the general population and subjects who were hospitalized for a nonsepsis diagnosis. The primary outcomes were all-cause mortality, major adverse cardiovascular events, myocardial infarction, heart failure, stroke, and sudden cardiac death or ventricular arrhythmia.Measurements and Main Results: Compared with matched population control subjects, sepsis survivors had higher risks...

Objective To examine the risk of acute kidney injury (AKI) in a nationwide cohort of patients with type 2 diabetes initiating dipeptidyl peptidase-4 (DPP-4) inhibitors. Patients and Methods This nested case-control study of a cohort of adult DPP-4 inhibitor users with type 2 diabetes who were hospitalized for AKI between January 1, 2010, and December 31, 2013, was conducted using Taiwan's National Health Insurance Research Database. Each AKI case was matched with one control subject according to duration of follow-up, age, sex, urbanization level, monthly income, comorbidity severity, and well-known predisposing factors for AKI. Odds ratios (ORs) for AKI were calculated according to current, recent, or past use of DPP-4 inhibitors. Results A total of 6752 cases with AKI and 6752 matched controls were analyzed. The exposure prevalence of DPP-4 inhibitor use in the previous year was higher among patients with AKI (adjusted OR, 1.20; 95% CI, 1.05-1.36; P =.006). In a stratified analysis, the association was significant for current DPP-4 inhibitor use (adjusted OR, 1.26; 95% CI, 1.08-1.48; P =.004), but not for recent or past use. Conclusion In this large contemporary cohort, DPP-4 inhibitor users had an increased risk of AKI development compared with nonusers. Further research is warranted to investigate the mechanism underlying this association.

The 2014 Eighth Joint National Committee guidelines for hypertension management emphasize the upper limit of blood pressure (BP) as the target for treatment in the elderly population. Given the uncertainty regarding optimal BP range, we aimed to investigate the association between observed BP and subsequent mortality in older people.We extracted data from 128,765 participants ≥65 years of age who underwent annual health examinations in a retrospective, observational community-based study from 2001 to 2010. Seated BP was measured using an oscillometric device. The outcomes were all-cause and cardiovascular mortality.As compared to participants with systolic BP at 130 to 139 mm Hg, the risk of all-cause mortality was significantly higher among those with110 (adjusted hazard ratios [aHRs], 1.12; 95% confidence interval [CI], 1.05-1.20), 140 to 149 (aHR, 1.08; 95% CI, 1.03-1.14), 150 to 159 (aHR, 1.07; 95% CI, 1.01-1.17), 160 to 169 (aHR, 1.11; 95% CI, 1.04-1.19), and ≥170 mm Hg (aHR, 1.25; 95% CI, 1.17-1.33), whereas the differences were not significant for those with 110 to119 (aHR, 1.06; 95% CI, 1.00-1.12) and 120 to 129 mm Hg (aHR, 1.03; 95% CI, 0.97-1.08). Similarly, diastolic BP at 40 to 79 mm Hg was associated with the lowest risk of all-cause mortality. The J-shaped curve relationship between BP and cardiovascular mortality was also observed.Observed systolic and diastolic BP other than 110 to 139 and 40 to 79 mm Hg, respectively, were associated with a worse outcome. Our large cohort study supports the J-shaped mortality with observed BP in older people.

To evaluate the long-term survival rate of critically ill sepsis survivors following cardiopulmonary resuscitation on a national scale.Retrospective and observational cohort study.Data were extracted from Taiwan's National Health Insurance Research Database.A total of 272,897 ICU patients with sepsis were identified during 2000-2010. Patients who survived to hospital discharge were enrolled. Post-discharge survival outcomes of ICU sepsis survivors who received cardiopulmonary resuscitation were compared with those of patients who did not experience cardiopulmonary arrest using propensity score matching with a 1:1 ratio.None.Only 7% (n = 3,207) of sepsis patients who received cardiopulmonary resuscitation survived to discharge. The overall 1-, 2-, and 5-year postdischarge survival rates following cardiopulmonary resuscitation were 28%, 23%, and 14%, respectively. Compared with sepsis survivors without cardiopulmonary arrest, sepsis survivors who received cardiopulmonary resuscitation had a greater risk of all-cause mortality after discharge (hazard ratio, 1.38; 95% CI, 1.34-1.46). This difference in mortality risk diminished after 2 years (hazard ratio, 1.11; 95% CI, 0.96-1.28). Multivariable analysis showed that independent risk factors for long-term mortality following cardiopulmonary resuscitation were male sex, older age, receipt of care in a nonmedical center, higher Charlson Comorbidity Index score, chronic kidney disease, cancer, respiratory infection, vasoactive agent use, and receipt of renal replacement therapy during ICU stay.The long-term outcome was worse in ICU survivors of sepsis who received in-hospital cardiopulmonary resuscitation than in those who did not, but this increased risk of mortality diminished at 2 years after discharge.

Renin-angiotensin-aldosterone system blockers are the preferred antihypertensive medications in patients with diabetes and prior stroke. This study aimed to compare the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in terms of major adverse cardiac events (MACEs) in patients with diabetes who survived ischemic stroke.We conducted an observational, nationwide, propensity score-matched cohort study using Taiwan's National Health Insurance Research Database. Patients aged at least 20 years with type 2 diabetes who initiated ACEI (n = 15,959) or ARB (n = 23,929) use within 90 days after discharge for first ischemic stroke between January 2000 and December 2011 were allocated to ACEI and ARB groups, respectively. The primary outcomes were MACEs (myocardial infarction, ischemic stroke, and cardiovascular mortality). The secondary outcomes were hospitalization for acute kidney injury and hyperkalemia. Intention-to-treat and as-treated models were used.Intention-to-treat analysis showed no significant difference between the ACEI and ARB groups in the outcomes of MACEs [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.95-1.04], including ischemic stroke (HR, 1.01; 95% CI, 0.97-1.06), myocardial infarction (HR, 1.06; 95% CI, 0.95-1.18), and cardiovascular mortality (HR, 0.98; 95% CI, 0.91-1.06). As-treated analysis produced similar results. Additionally, the groups showed no difference in the risk of hospitalization for acute kidney injury or hyperkalemia.Our study supports the hypothesis that the risks of MACEs and two additional secondary outcomes in patients with diabetes who survived ischemic stroke did not differ according to ACEI versus ARB use.

Background Previous studies have suggested a close correlation between gastroesophageal reflux disease (GERD) and various respiratory disorders. However, the association between GERD and tuberculosis (TB) remains unexplored. Methods Using data retrieved from Taiwan's National Health Insurance Research Database from 2000 to 2009, this longitudinal nationwide cohort study included a total of 63,930 patients with GERD and controls matched by age, sex and comorbidities. Risk factors associated with the development of pulmonary TB (PTB) were investigated. Results Active PTB was documented in 65 (0.20%) patients with GERD and 41 (0.13%) matched cohorts within 1 year of GERD diagnosis. The incidence rate of PTB in the GERD group and the matched cohort was respectively 24.1 and 15.2 cases per 10,000 person-years. In multivariate analysis, GERD was an independent risk factor for PTB (adjusted HR 1.63, 95%CI 1.10-2.40, P = 0.015). Among patients with GERD, independent predictors for PTB included older age, male sex, chronic obstructive pulmonary disease, asthma and exposure to proton pump inhibitors (PPIs). Conclusion Patients with GERD have a significantly increased risk of PTB within 1 year of GERD diagnosis. Exposure to PPIs is an independent predictor for PTB among patients with GERD.

Background and objective Recent observational studies have shown that sleep apnoea (SA) is associated with increased risk of incident CKD. However, the contribution of SA relative to common traditional CKD risk factors remains unknown. The aims of this study were to investigate the long-term risk of incident CKD events following SA diagnosis and compare the relative contributions of SA, diabetes and hypertension. Methods Data were retrieved from Taiwan's National Health Insurance Research Database during the period between 2000 and 2010 for this retrospective cohort study. The cohorts are composed of patients (age ≥ 20 years) newly diagnosed with SA and matched subjects without SA. The two cohorts were followed until the occurrence of CKD, death or the end of 2010. Results The sample is composed of 43 434 individuals (8687 patients with SA and 34 747 matched non-SA subjects). A total of 157 new CKD events in patients with SA and 298 events in the matched non-SA cohort were recorded during a mean follow-up period of 3.9 years (incidence rates, 4.5 and 2.2/per 1000 person-years). The risk of CKD development was greater among patients with SA than in the matched non-SA cohort (adjusted hazard ratio (aHR) 1.58, 95% confidence interval ( CI): 1.29–1.94). The contribution of SA to the CKD hazard was similar to that of hypertension (aHR 1.17, 95% CI: 0.68–2.01, P = 0.56), whereas that of diabetes remained significantly higher (aHR 2.17, 95% CI: 1.21–3.90, P = 0.01). Conclusion SA was associated with an increase in the risk of CKD incidence similar to that of hypertension. See Editorial, page 578

Background— Whether oral anticoagulant use should be considered in patients undergoing hemodialysis with atrial fibrillation (AF) remains controversial because of the uncertainty regarding risk-benefit assessments. The purpose of this study was to investigate the risk of ischemic stroke in patients undergoing hemodialysis with new-onset AF, in comparison with those without arrhythmia. Methods and Results— This nationwide, population-based, propensity score–matched cohort study used data from Taiwan’s National Health Insurance Research Database during 1998 to 2011 for patients on hemodialysis with new-onset nonvalvular AF and matched subjects without arrhythmia. The clinical end points were ischemic stroke (fatal or nonfatal), all-cause death, and other serious adverse cardiovascular events. In comparison with the matched cohort, patients with AF (n=6772) had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.13–1.43), all-cause death (aHR, 1.59; 95% CI, 1.52–1.67), in-hospital cardiovascular death (aHR, 1.83; 95% CI, 1.71–1.94), myocardial infarction (aHR, 1.33; 95% CI, 1.17–1.51), and hospitalization for heart failure (aHR, 1.90; 95% CI, 1.76–2.05). After considering in-hospital death as a competing risk, AF significantly increased the risk of heart failure (HR, 1.56; 95% CI, 1.45–1.68), but not those of ischemic stroke and myocardial infarction. Additionally, the predictive value of the CHA 2 DS 2 –VASc score for ischemic stroke was diminished in the competing-risk model. Conclusions— The risk of stroke was only modestly higher in patients undergoing hemodialysis with new-onset AF than in those without AF, and it became insignificant when accounting for the competing risk of in-hospital death.

Background Previous studies have demonstrated that high estimated glomerular filtration rate (eGFR) is paradoxically associated with an increased risk of mortality, and the association becomes more predominant in older people. However, the role of malnutrition–inflammation–cachexia syndrome (MICS) in the association between eGFR and mortality has never been explored. Methods We conducted a community-based cohort study using data from the Taipei City Elderly Health Examination Database, collected during the period 2001–10. All participants aged ≥65 years were included and stratified by the absence or presence of MICS, which is defined as the presence of at least one of the following markers: body mass index

Background The comorbidity profile, especially cancer risk, of narcoleptic patients has seldom been explored. We used a nationwide database to evaluate the risk of cancer among adult narcoleptic patients. Methods We conducted the cohort study using National Health Insurance Research Database from 2000 to 2009. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort with that of the general population. Results 2833 narcoleptic patients were identified after excluding patients with antecedent malignancy and age younger than 18 years old. The study cohort was observed for 15,913 person-years during a 10-year period. The median follow-up interval was 5.6 ± 3.0 years. Seventy-four cancers occurred in during the follow-up. The risk of all cancers was found significantly increased in adult narcoleptic patients (SIR 1.32; 95% CI, 1.04–1.66, p = 0.0248). Regarding sex, the overall cancer risk was increased in female patients (SIR 1.52; 95% CI, 1.05–2.13, p = 0.026). Furthermore, females were found to have more head and neck cancers (SIR 6.17; 95% CI, 1.66-15.80, p = 0.009) and gastric cancers (SIR 4.87; 95% CI, 1.31–12.48, p = 0.02). For males, the incidence of overall and specific cancer types was not significantly increased. Conclusions Adult narcoleptic patients had a higher risk for cancer. Further research is warranted to elucidate the mechanism underlying its association.

In a large observational database study of add-on treatments to metformin, the addition of dipeptidyl peptidase-4 (DPP-4) inhibitors was associated with a lower risk for all-cause mortality, stroke...

Background The link between elevated serum uric acid ( SUA ) levels and cardiovascular disease ( CVD )–related mortality in the elderly population remains inconclusive. Nutritional status influences both SUA and CVD outcomes. Therefore, we investigated whether SUA ‐predicted mortality and the effect‐modifying roles of malnourishment in older people. Methods and Results A longitudinal Taiwanese cohort including 127 771 adults 65 years and older participating in the Taipei City Elderly Health Examination Program from 2001 to 2010 were stratified by 1‐mg/dL increment of SUA . Low SUA (2 . Study outcomes were all‐cause and CVD ‐related mortality. Cox models were used to estimate hazard ratios ( HRs ) of mortality, after adjusting for 20 demographic and comorbid covariates. Over a median follow‐up of 5.8 years, there were 16 439 all‐cause and 3877 CVD ‐related deaths. Compared with the reference SUA strata of 4 to SUA HR , 1.16; 95% confidence interval, 1.07–1.25) and ≥8 mg/dL ( HR , 1.13; confidence interval, 1.06–1.21), with progressively elevated risks at both extremes. Similarly, increasingly higher CVD ‐related mortality was found at the SUA level HR , 1.19; confidence interval, 1.00–1.40) and ≥7 mg/dL ( HR , 1.17; confidence interval, 1.04–1.32). Remarkably, among the low SUA (CVD ‐related mortality. This modifying effect of malnourishment remained consistent across subgroups. Conclusions SUA ≥8 or CVD ‐related mortality in the elderly, particularly in those with malnourishment.

The reported incidence and risk factors mediating seizures in Alzheimer's disease (AD) have been extremely inconsistent and relevant data is lacking in Asia. We investigated the incidence rate and risk of seizures in AD and in a large, nationwide cohort from Han Chinese. A retrospective population-based study was conducted on the data from Taiwan's National Health Insurance Research Database from 2000 to 2010. To reduce selection bias, we applied propensity scores, wherein 981 patients with AD were matched to 3835 non-AD controls from a pool of 1000,000 randomly sampled cohort dataset. This approach was based on age, sex, comorbidities and previous brain conditions. Incidence rate, cumulative incidence and hazard ratios (HRs) were estimated. During the 10-year follow-up period (mean follow-up time, 4.02 years), 44 out of 937 AD patients (4.7%) developed seizures. The incidence rate in the AD cohort (11.9 per 1000 person-years) was higher than that in the matched cohort (5.7 per 1000 person-years), with an adjusted HR of 1.85 (95% confidence interval [CI], 1.20-2.83, p=0.005). The mean duration from the diagnosis of AD to the occurrence of seizure is 3.6 years. The Cox regression analysis revealed that AD itself is a significant predictor after adjustment for confounders (HR=2.01, 95% CI, 1.40-2.90, p

Background The association between periodontal disease and chronic kidney disease in older people is controversial, and evidence for a causal link between kidney function decline and subsequent mortality risk is limited. Study Design Longitudinal, observational, community-based cohort study. Setting & Participants Participants were citizens 65 years or older who received the Taipei City Government–sponsored Annual Elderly Health Examination Program during 2005 to 2010, including dental status assessment and biochemical examinations. Predictors Participants with periodontal disease defined by the World Health Organization Community Periodontal Index of Treatment Need criteria. Outcomes All-cause and cardiovascular mortality and estimated glomerular filtration rate (eGFR) decline ≥ 30% over 2 years. Results Of 100,263 study participants, 13,749 (13.7%) had periodontal disease. In a mean follow-up of 3.8 years, all-cause and cardiovascular mortality rates in those with periodontal disease (11.5% and 2.6%, respectively) were higher compared with those without periodontal disease (6.7% and 1.6%, respectively). After adjustment for demographic characteristics, comorbid conditions, and biochemistry data, adjusted HRs for all-cause and cardiovascular mortality were 1.34 (95% CI, 1.26-1.42) and 1.25 (95% CI, 1.13-1.41), respectively. The frequency of eGFR decline ≥ 30% over 1-, 2-, and 3-years' follow-up in those with periodontal disease was 1.8%, 3.7%, and 4.0%, respectively. In a logistic regression model, adjusted ORs of the detrimental effect of periodontal disease on 30% eGFR decline in participants over 1-, 2-, or 3-years' follow-up were 1.03 (95% CI, 0.85-1.25), 1.62 (95% CI, 1.41-1.87), and 1.59 (95% CI, 1.37-1.86), respectively. In subgroup analyses according to age, sex, and comorbid conditions, risks for eGFR decline and mortality remained consistent. Limitations Results may not be generalizable to other non-Asian ethnic populations. Conclusions The results indicate that periodontal disease is a risk factor for all-cause and cardiovascular mortality and eGFR decline ≥ 30% over 2 to 3 years in older people.

Background Retinal vein occlusion (RVO) is the second most common retinal vascular disease, with peak incidence at 70years of age. However, the bidirectional association between the risk of comorbidities and the diagnosis of RVO in this population is uncertain. Methods A population-based cohort of 1,784,960 patients 70years of age and older retrieved from the Taiwan National Health Insurance Research Database between 2000 and 2010. Risks of comorbidities were assessed 5years before and after the diagnosis of RVO. Results In our study, 3393 subjects had central RVO (CRVO) and 6688 subjects had branch RVO (BRVO). Before the diagnosis of RVO, patients showed increased risks for the following comorbidities: hypertension (odds ratio [OR]=1.83, 95% confidence interval [CI], 1.74–1.93), dyslipidemia (OR=1.29, [1.23–1.35]), DM (OR=1.29, [1.23–1.35]), liver disease (OR=1.22, [1.16–1.29]), renal disease (OR=1.30, [1.23–1.37]), and cerebrovascular disease (OR=1.16, [1.11–1.21]). After the diagnosis of RVO, patients were at greater risk of developing DM (adjusted hazard ratio [AHR]=1.12, [1.06–1.19]), PAD (AHR=1.17, [1.08–1.27]), and MACE (AHR=1.35, [1.25–1.46]); however, the risk of all-cause mortality was unchanged. Elderly patients with CRVO had a significantly higher risk of all-cause mortality (AHR=1.09, [1.02–1.17]), whereas patients with BRVO showed no significant differences in mortality. Conclusion This study suggests bidirectional association between the risk of comorbidities and the diagnosis of RVO in an elderly population.

Summary Objective The potential association between healthcare workers (HCWs) and the risk of clinically active tuberculosis (TB) in countries with intermediate TB burdens remains unclear. Methods A nationwide, population-based cohort study was performed by using Taiwan National Health Insurance Database during 2000–2010. We included HCWs and non-HCWs without history of tuberculosis matched at a 1:1 ratio according to age, sex, monthly income, underlying comorbidities, and concomitant medications. All subjects were followed from the date of enrollment until TB occurrence, death, or 31 December 2010. Results The study population comprised 11,811 healthcare workers and 11,811 matched subjects. 62 HCWs and 38 control subjects developed TB during a median follow-up period of 9.4 years. The incidence of TB was higher among HCWs than among matched subjects (61.08 vs . 37.81 per 100,000 person-years). The risk of TB was also greater among HCWs (adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.08–2.43), particularly for pulmonary TB in comparison with extrapulmonary TB (aHR, 1.56; 95% CI, 1.02–2.39). Among different job categories of HCWs, we found that only nurses had a significantly increased risk of developing TB (aHR, 2.55; 95% CI, 1.37–4.72) compared to the matched cohort. Conclusions HCWs are associated independently with a higher risk of developing TB in this intermediate-burden country. Therefore, the importance of TB surveillance among HCWs should be emphasized.

Background— Substantial infective endocarditis (IE)–related morbidity and mortality may occur even after successful treatment. However, no previous study has explored long-term hard end points (ie, stroke, myocardial infarction, heart failure, cardiovascular death) in addition to all-cause mortality in IE survivors. Methods and Results— A nationwide population-based cohort study was conducted among IE survivors identified with the use of the Taiwan National Health Insurance Research Database during 2000 to 2009. IE survivors were defined as those who survived after discharge from first hospitalization with a diagnosis of IE. A total of 10 116 IE survivors were identified. IE survivors were matched to control subjects without IE at a 1:1 ratio through the use of propensity scores. The primary outcomes were stroke, myocardial infarction, readmission for heart failure, and sudden cardiac death or ventricular arrhythmia. The secondary outcomes were repeat IE and all-cause mortality. Compared with the matched cohort, IE survivors had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.59; 95% confidence interval [CI], 1.40–1.80), hemorrhagic stroke (aHR, 2.37; 95% CI, 1.90–2.96), myocardial infarction (aHR, 1.44; 95% CI, 1.17–1.79), readmission for heart failure (aHR, 2.24; 95% CI, 2.05–2.43), sudden death or ventricular arrhythmia (aHR, 1.69; 95% CI, 1.44–1.98), and all-cause death (aHR, 2.27; 95% CI, 2.14–2.40). Risk factors for repeat IE were older age, male sex, drug abuse, and valvular replacement after an initial episode of IE. Conclusion— Despite treatment, the risk of long-term major adverse cardiac events was substantially increased in IE survivors.

Objective Whether migraine is associated with urinary calculi is an unresolved issue, although topiramate, a migraine-preventive agent, is known to contribute to this complication. This study investigates the association between migraine and the risk of urinary calculi. Methods We identified a total of 147,399 patients aged ≥18 years with migraine diagnoses recorded in the Taiwan National Health Insurance Research Database between 2005 and 2009. Each patient was randomly matched with one individual without headache using propensity scores. All participants were followed from the date of enrollment until urinary calculi development, death, or the end of 2010. Results The risk of urinary calculi was greater in the migraine than the control cohort (adjusted hazard ratio (aHR), 1.58; 95% confidence interval (CI), 1.52–1.63; p Conclusions Our study showed migraine was associated with an increased risk of urinary calculi, independent of topiramate use. A higher frequency of clinic visits was associated with a greater risk.

Aims Increases in the systemic vasodilator adrenomedullin and the renal vasoconstrictors thromboxane A2 (TXA2) in cirrhotic patients are pathogenic factors for the development of functional acute-kidney-injury, including pre-renal azotemia (PRA) and hepatorenal syndrome (HRS), which is associated with high mortality. This study aims to find biomarkers which can diagnose HRS in early stage for treating it as soon as possible. Methods Acute decompensated cirrhotic patients who had been admitted to hospital were enrolled in this prospective cohort study. Blood and urinary samples were collected immediately after admission. In addition to initially categorizing acute-kidney-injury cases into PRA, acute tubular-necrosis (ATN) and HRS groups, their final diagnosis was adjudicated by a nephrologist and a hepatologist who checked the corrected and misclassification rates for significant biomarkers. Results The cutoff values for serum adrenomedullin and urinary TXB2, when used as predictors for functional acute kidney injury {[adrenomedullin] >283 pg/mL, urinary TXB2 > 978 (pg/mg urinary creatinine)}, for HRS {[adrenomedullin] >428, urinary TXB2 > 1604}, and for good terlipressin plus albumin treatment responders {[adrenomedullin] > 490; urinary TXB2 > 1863}, were observed. HRS patients who can't be treated, due to high mortality, had significantly higher serum adrenomedullin and urinary TXB2 levels compared to HRS patients receiving standard treatment. In addition to predicting 60-day mortality, a combination of these two markers further increased diagnostic accuracy for HRS among functional acute-kidney-injury. Conclusions Prompt diagnosis of HRS by differentiating it from PRA and ATN can be achieved by using serum adrenomedullin and urinary TXB2 in acute de-compensated cirrhotic patients. In combination with severe clinical courses, these two markers are useful to select HRS patients who can't be treated.

Background Long‐term cardiovascular outcomes after sepsis in patients with chronic kidney disease are not well known. We aimed to examine the risk of subsequent cardiovascular events in patients with chronic kidney disease discharged after hospitalization for sepsis in Taiwan. Methods and Results Using complete claims data for patients with chronic kidney disease from Taiwan's National Health Insurance Research Database, we identified patients with sepsis who survived hospitalization between 2000 and 2010. Each sepsis survivor was propensity score–matched to one nonsepsis hospitalized control patient. Cox regression models were used to estimate the hazard ratios ( HR s) of clinical outcomes, including major adverse cardiovascular events (myocardial infarction and ischemic stroke), hospitalization for heart failure, and all‐cause death. Among 66 961 sepsis survivors, the incidence rates of all‐cause mortality and major adverse cardiovascular events during the study period were 288.51 and 47.05 per 1000 person‐years, respectively. In comparison with matched hospitalized nonsepsis control patients, sepsis survivors had greater risks of major adverse cardiovascular events ( HR , 1.42; 95% CI , 1.37–1.47), myocardial infarction ( HR , 1.39; 95% CI , 1.32–1.47), ischemic stroke ( HR , 1.46; 95% CI , 1.40–1.52), hospitalization for heart failure ( HR , 1.55; 95% CI , 1.51–1.59), and all‐cause mortality ( HR , 1.56; 95% CI , 1.54–1.58). The results remained unchanged in analyses of several subgroups of patients, and were similar in analyses accounting for the competing risk of death. Conclusions Our findings highlight the association of sepsis with a significantly increased long‐term risk of cardiovascular events among survivors in the chronic kidney disease population.

End-stage renal disease (ESRD) patients are more prone to infectious disease because of their immunocompromised status. However, the association between pyogenic liver abscess (PLA) and ESRD remains not clear. The aim of our study is to evaluate the incidence, risk factors, and outcomes of PLA in ESRD patients. We recruited all incident ESRD patients from the Taiwan National Health Insurance database from 1998 to 2006. The incidence rate of PLA in ESRD patients was compared with that of a randomly selected non-ESRD control group matched for age, sex gender, Charlson comorbidity score, diabetes mellitus, and cirrhosis. Among the 57,761 incident dialysis patients, there were 538 cases of PLA. The incidence rate of PLA was 18.20 per 10,000 person-years in the ESRD cohort and 6.34 per 10,000 person-years in matched control cohort. The rate of PLA was significantly higher in the ESRD cohort (hazard ratio 3.63, 95% confidence interval 2.83–4.65, P

Background Cluster headache (CH) is well known to show a seasonal predilection; however, the impact of temperature and other meteorological factors on cluster periods (or bouts) has not been established. Methods This nationwide survey included 758 patients with episodic CH retrieved from the Taiwan National Health Insurance Research Database from 2005 to 2009. Corresponding meteorological recordings were obtained from the Central Weather Bureau. A case-crossover study design was used to investigate the association between cluster periods and meteorological factors. Results A total of 2452 episodes of cluster periods were recorded. The cluster periods were most frequent in the autumn and least frequent in the winter. Seasonal changes from winter to spring and from autumn to winter also increased the frequency of cluster periods. The risk of cluster periods increased when there was a higher mean temperature on event days (odds ratio (OR), 1.014, 95% confidence interval (CI), 1.005–1.023, p = 0.003) or within seven to 56 days. Either an increase or a decrease in temperature (0.05℃/day) following a warm period (mean temperature ≥26℃) was associated with the onset of cluster periods. In contrast, a greater increase in temperature (0.15℃/day) following a cold period (mean temperature Discussion Our study shows that temperature is associated with precipitating or priming cluster periods. The influence depends on the temperature of the preceding periods.

Background and objectives We aimed to investigate the benefits and risks of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent (DES) implantation in patients undergoing hemodialysis. Design, setting, participants, & measurements A nested case-control analysis of patients on hemodialysis after receipt of DES and DAPT treatment was conducted using data from Taiwan’s National Health Insurance Research Database for the period 2007–2011. Cases of myocardial infarction or death within 1 year after DES implantation were matched one-to-one with control patients. Odds ratios were calculated to compare DAPT continuation with discontinuation. Additionally, a propensity score–adjusted 6-month landmark cohort analysis was also conducted to evaluate the long-term benefits and risks of prolonged (>6 months) compared with ≤6 months of DAPT use. The primary outcomes were death and myocardial infarction. The secondary outcomes were ischemic stroke, revascularization, and major bleeding. Results In the nested case-control analysis, patients who continued DAPT had a lower rate of death or myocardial infarction within 1 year after receipt of a DES (adjusted odds ratio, 0.54; 95% confidence interval, 0.36 to 0.81; P =0.003), whereas this association became statistically nonsignificant when compared with patients who discontinued DAPT for the period between 6 and 12 months after receipt of a DES (adjusted odds ratio, 1.51; 95% confidence interval, 0.75 to 3.04). In the propensity score–adjusted cohort analysis, >6 months of DAPT use was not associated with different primary or secondary outcomes than shorter-term use. Conclusions Our findings support that the clinical effectiveness of extended DAPT in a hemodialysis population may be tempered after 6 months post-DES implantation.

Genetic variants and dysfunctional monocyte had been reported to be associated with infection susceptibility in advanced cirrhotic patients. This study aims to explore genetic predictive markers and relevant immune dysfunction that contributed to severe sepsis in febrile acute de-compensated cirrhotic patents. Polymorphism analysis of candidate genes was undergone in 108 febrile acute de-compensated cirrhotic patients and 121 healthy volunteers. Various plasma inflammatory/regulatory cytokines, proportion of classical (CD 16-, phagocytic) and non-classical (CD16+, inflammatory) monocytes, lipopolysaccharide (LPS)-stimulated toll-like receptor 4 (TLR4) and intracellular/extracellular cytokines on cultured non-classical monocytes, mCD14/HLA-DR expression and phagocytosis of classical monocytes were measured. For TLR4+896A/G variant allele carriers with severe sepsis, high plasma endotoxin/IL-10 inhibits HLA-DR expression and impaired phagocytosis were noted in their classical monocyte. In the same group, increased non-classical monocyte subset, enhanced LPS-stimulated TLR4 expression and TNFα/nitrite production, and systemic inflammation [high plasma soluble CD14 (sCD14) and total nitric oxide (NOx) levels] were noted. For CD14-159C/T variant allele carriers with severe sepsis, persist endotoxemia inhibited mCD14/HLA-DR expression and impaired phagocytosis of their classical monocyte. In the same group, increased non-classical monocyte subset up-regulated TLR4-NFκB-iNOS and p38MAPK pathway, stimulated TNFα/nitrite production and elicited systemic inflammation. In febrile acute de-compensated cirrhotic patients, TLR4+896A/G and CD14-159C/T polymorphisms-related non-classical and classical monocytes dysfunction resulted in increased severe sepsis risk. Malnutrition, high plasma endotoxin and sCD14 levels, single TLR4+896A/G or CD14-159C/T variant allele carriers and double variant allele carriers are significant predictive factors for the development of severe sepsis among them.

BACKGROUND: In postmarketing surveillance, the US Food and Drug Administration has reported the development of lung masses, thyroid cancer, and skin cancer after amiodarone therapy. METHODS: Using the Taiwan National Health Insurance Research database, the authors conducted a population-based cohort study. Patients who were treated with amiodarone between 1997 and 2008 were enrolled. Those with antecedent cancer were excluded. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort with that of the general population. A multivariate Cox regression model was used to evaluate the association between cumulative defined daily doses (cDDDs) of amiodarone and cancer occurrence. RESULTS: The study included 6418 subjects, with a median follow-up of 2.57 years. A total of 280 patients developed cancer. The risk of cancer increased with borderline significance (SIR, 1.12; 95% confidence interval [95% CI], 0.99-1.26 [P = .067]). Male patients had a higher risk (SIR, 1.18; 95% CI, 1.02-1.36 [P = .022]). The total cohort of patients and the male patients with > 180 cDDDs within the first year were found to have SIRs of 1.28 (95% CI, 1.00-1.61; P = .046) and 1.46 (95% CI, 1.11-1.89; P = .008), respectively. After adjustment for age, sex, and comorbidities, the hazards ratio was 1.98 (95% CI, 1.22-3.22; P = .006) for the high tertile of cDDDs compared with the low tertile. CONCLUSIONS: The results of the current study indicate that amiodarone may be associated with an increased risk of incident cancer, especially in males, with a dose-dependent effect. Cancer 2013;119:1699–1705. © 2013 American Cancer Society.

The objective of this study was to evaluate the risks of acute cholecystitis among end-stage renal disease patients and compare the incidence between two dialysis modality.In this retrospective cohort study, records of fifty thousand end-stage renal disease patients older than 20 years of age from 1998 to 2007 and an age, gender, Charlson's score, diabetes, and dyslipidemia matched control cohort were retrieved from Taiwan National Health Insurance Research Database. Hospitalizations for acute cholecystitis were retrieved using ICD-9-CM diagnosis codes and ICD-9-CM operation codes from in-patient claims.The incidence rates were 5.8 per 1000 patient-years in the end-stage renal disease patients and 0.92 per 1000 patient-years in the control group. End-stage renal disease was an independent risk factor for acute cholecystitis. In the end-stage renal disease patients, independent risk factors were old age, higher Charlson's score, diabetes, severe liver disease, atrial fibrillation, and haemodialysis (all p0.05). However, the peritoneal dialysis patients had a higher mortality rate after developing acute cholecystitis.Acute cholecystitis is not uncommon in end-stage renal disease patients. The independent risk factors were older age, higher Charlson's score, atrial fibrillation, severe liver disease, diabetes, and dialysis modality. Haemodialysis patients had a higher risk of acute cholecystitis than PD patients.

Summary Background The aim of this study is to investigate the "weekend effect" and early mortality of patients with severe sepsis. Methods Using the Taiwanese National Healthcare Insurance Research Database, all patients who were hospitalized for the first time with an episode of severe sepsis between January 2000 and December 2011 were identified and the short-term mortality of patients admitted on weekdays was compared to those admitted on weekends. The primary endpoint was 7-day mortality. The secondary endpoints were 14 and 28-day mortality. Results A total of 398,043 patients were identified to have had the diagnosis of severe sepsis. Compared with patients admitted on weekends, patients admitted on weekdays had a lower 7-day mortality rate (adjusted odds ratio [OR] 0.89, 95% confidential interval [CI] 0.87–0.91), 14-day mortality rate (adjusted OR 0.92, 95% CI 0.90–0.93), and 28-day mortality rate (adjusted OR 0.97, 95% CI 0.95–0.98). This "weekend effect" was maintained every year throughout the 11-year study period. Conclusions Patients with severe sepsis are more likely to die in the hospital if they were admitted on weekends than if they were admitted on weekdays.

Background Recent clinical trials have evaluated the cardiovascular outcomes of dipeptidyl peptidase-4 ( DPP-4) inhibitors in patients with type 2 diabetes mellitus (T2DM), but those with end-stage renal disease (ESRD) were ineligible for participation in these trials. We aimed to characterize the impact of DPP-4 inhibitors on major adverse cardiovascular events (MACEs) in patients with T2DM and ESRD undergoing chronic dialysis. Methods This nationwide observational study utilized data from 3556 patients aged ≥20years with T2DM and ESRD who initiated treatment with DPP-4 inhibitors between 1 March 2009 and 31 June 2013, retrieved from Taiwan's National Health Insurance Research Database. Each DPP-4 inhibitor user was matched to a non-user control subject using propensity scores. The primary outcomes were all-cause mortality and MACEs (ischemic stroke and myocardial infarction). The secondary outcomes were hospitalization for heart failure and hypoglycemia. All subjects were followed until death or 31 December 2013. Results Compared with non-users, DPP-4 inhibitor users had lower risks of all-cause mortality (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.39–0.47), MACEs (HR 0.76, 95% CI 0.65–0.90), and ischemic stroke (HR 0.77, 95% CI 0.61–0.97); the risks of myocardial infarction and hospitalization for heart failure and hypoglycemia did not differ. This treatment effect remained consistent in subgroup analyses according to age, sex, comorbidities, dialysis modality, and insulin use. Conclusions In this nationwide ESRD cohort, DPP-4 inhibitor use was associated with reduced risks of all-cause mortality and ischemic stroke.

Background: Angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are effective treatments for diabetic retinopathy, but randomized trials and meta-analyses comparing their effects on macrovascular complications have yielded conflicting results. We compared the effectiveness of these drugs in patients with pre-existing diabetic retinopathy in a large population-based cohort. Methods: We conducted a propensity score–matched cohort study using Taiwan’s National Health Insurance Research Database. We included adult patients prescribed an ACE inhibitor or ARB within 90 days after diagnosis of diabetic retinopathy between 2000 and 2010. Primary outcomes were all-cause death and major adverse cardiovascular events (myocardial infarction, ischemic stroke or cardiovascular death). Secondary outcomes were hospital admissions with acute kidney injury or hyperkalemia. Results: We identified 11 246 patients receiving ACE inhibitors and 15 173 receiving ARBs, of whom 9769 patients in each group were matched successfully by propensity scores. In the intention-to-treat analyses, ARBs were similar to ACE inhibitors in risk of all-cause death (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.87–1.01) and major adverse cardiovascular events (HR 0.95, 95% CI 0.87–1.04), including myocardial infarction (HR 1.03, 95% CI 0.88–1.20), ischemic stroke (HR 0.94, 95% CI 0.85–1.04) and cardiovascular death (HR 1.01, 95% CI 0.88–1.16). They also did not differ from ACE inhibitors in risk of hospital admission with acute kidney injury (HR 1.01, 95% CI 0.91–1.13) and hospital admission with hyperkalemia (HR 1.01, 95% CI 0.86–1.18). Results were similar in as-treated analyses. Interpretation: Our study showed that ACE inhibitors were similar to ARBs in risk of all-cause death, major adverse cardiovascular events and adverse effects among patients with pre-existing diabetic retinopathy.

Acute appendicitis in patients with end-stage renal disease (ESRD) poses a diagnostic challenge. Delayed surgery can contribute to higher morbidity and mortality rates. However, few studies have evaluated this disease among ESRD patients. Our study focused on the lack of data on the incidence and risk factors of acute appendicitis among ESRD patients and compared the outcomes in patients who underwent different dialysis modalities. This national survey was conducted between 1997 and 2005 and included ESRD patients identified from the Taiwan National Health Insurance database. The incidence rate of acute appendicitis in ESRD patients was compared with that in randomly selected age-, sex-, and Charlson comorbidity score-matched non-dialysis controls. A Cox regression hazard model was used to identify risk factors. Among 59,781 incident ESRD patients, matched one-to-one with controls, there were 328 events of acute appendicitis. The incidence rate of 16.9 per 10,000 person-years in the ESRD cohort was higher than that in the control cohort (p = 0.003). The independent risk factors were atrial fibrillation (hazard ratio [HR], 2.08), severe liver disease (HR, 1.74), diabetes mellitus (HR, 1.58), and hemodialysis (HR, 1.74). Compared with the control cohort, subsequent perforation and mortality rates of acute appendicitis were also higher in the ESRD cohorts. There was no effect of dialysis modality on the patient outcomes. ESRD patients had a higher risk for acute appendicitis and poorer outcomes than non-dialysis populations. A careful examination of ESRD patients presenting with atypical abdominal pain to avoid misdiagnosis is extremely important to prevent delayed surgery.

Background Tuberculosis (TB) has been reported to increase morbidity after kidney transplantation and pose a therapeutic challenge. However, population-based research, specifically focused on the association between kidney transplantation and subsequent pulmonary or extrapulmonary TB, is lacking. Methods A nationwide population-based study was conducted using Taiwan's National Health Insurance Research Database, which provided claims data belonging to kidney transplant recipients during 1997–2006. Multivariate analysis was used to identify independent risk factors for TB after kidney transplantation. Kaplan-Meier survival analysis was used to assess the outcome of patients with TB. Results Among 4554 kidney transplant recipients over the 10-year period, 109 (2.4%) patients with newly diagnosed TB were identified: 75 patients with only pulmonary involvement, and 34 with extrapulmonary spread. The incidence of kidney transplant recipients developing TB was 638 per 100,000 person-years. The independent risk factors for post-transplant TB included cyclosporine-based immunosuppressant agents during the first year after kidney transplantation (odds ratio [OR]: 1.98, P = 0.001), hepatitis C infection (OR: 1.79, P = 0.024), and chronic obstructive pulmonary disease (OR: 1.50, P = 0.041). Kidney transplant recipients who developed TB had a lower 5-year survival rate than those who did not (78.6% vs. 93.4%, P = 0.001). Conclusions Kidney transplant recipients in Taiwan did have a high risk of TB infection, with high proportion of extrapulmonary spread. Physicians need to be vigilant in surveying for TB in kidney transplantation, especially in high-risk patients.

Nitric oxide (NO) is a pivotal vasoactive substance modulating arteriovenous fistula (AVF) patency for hemodialysis (HD). Since genetic background could be the predicting factor of AVF malfunction, we aimed to investigate whether the NO-related genotype polymorphisms determine AVF survival rates.This is a retrospective, observational, multi-center study involving eight HD units in Taiwan, enrolled 580 patients initiating maintenance HD via AVFs. Genotype polymorphisms of NO-biosynthesis regulating enzymes (DDAH-1, DDAH-2, eNOS and PRMT1) were compared between HD patients with (n = 161) and without (n = 419) history of AVF malfunction. Subgroup analyses by gender were performed to evaluate the genetic effect in difference sexes.In overall population, statistically significant associations were not found between AVF malfunction and the genetic polymorphisms. In the male subgroup (n = 313), a single nucleotide polymorphism (SNP) of PRMT1, rs10415880 (IVS9-193 A/G), showed a significant association with AVF malfunction. Male patients with AA/AG genotype had inferior AVF outcomes compared to GG genotype, regarding primary patency (70.6% vs. 40.9%, p = 0.001), assisted primary patency (81.0% vs. 58.4%, p 0.001) and secondary patency (83.7% vs. 63.3%, p 0.001) at a 5-year observation period. From multivariate Cox regression model, the AA/AG genotypes of PRMT1 were an independent risk factor for AVF malfunction in men (HR: 4.539, 95% CI 2.015-10.223; p 0.001). However, such associations were not found in women.rs10415880, the SNP of PRMT1 could be a novel genetic marker associated with AVF malfunction risk in male HD patients. Those with AA and AG genotypes of rs10415880 may predict a poorer long-term patency of AVF.

Background: The 2006 Kidney Disease Outcomes Quality Initiative guidelines suggest twice-weekly or incremental hemodialysis for patients with substantial residual kidney function (RKF). However, in most affluent nations de novo and abrupt transition to thrice-weekly hemodialysis is routinely prescribed for all dialysis-naïve patients regardless of their RKF. We review historical developments in hemodialysis therapy initiation and revisit twice-weekly hemodialysis as an individualized, incremental treatment especially upon first transitioning to hemodialysis therapy. Summary: In the 1960's, hemodialysis treatment was first offered as a life-sustaining treatment in the form of long sessions (≥10 hours) administered every 5 to 7 days. Twice- and then thrice-weekly treatment regimens were subsequently developed to prevent uremic symptoms on a long-term basis. The thrice-weekly regimen has since become the ‘standard of care' despite a lack of comparative studies. Some clinical studies have shown benefits of high hemodialysis dose by more frequent or longer treatment times mainly among patients with limited or no RKF. Conversely, in selected patients with higher levels of RKF and particularly higher urine volume, incremental or twice-weekly hemodialysis may preserve RKF and vascular access longer without compromising clinical outcomes. Proposed criteria for twice-weekly hemodialysis include urine output >500 ml/day, limited interdialytic weight gain, smaller body size relative to RKF, and favorable nutritional status, quality of life, and comorbidity profile. Key Messages: Incremental hemodialysis including twice-weekly regimens may be safe and cost-effective treatment regimens that provide better quality of life for incident dialysis patients who have substantial RKF. These proposed criteria may guide incremental hemodialysis frequency and warrant future randomized controlled trials.