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ObjectivesAnimal and ex vitro studies suggested lipid-lowering agents (LLAs) may be used as an adjunct to standard anti- tuberculosis (TB) treatment. No human study has been conducted to date. Using the Taiwan National Health Insurance Research Database (NHIRD), the current population-based cohort study sought to examine the association between use of LLAs and outcomes of patients with pulmonary TB receiving anti-TB treatment.MethodsUsing a NHIRD from 2003 to 2010, this population-based cohort study retrospectively examined the association between LLAs (statins or fibrates) and the outcomes of patients with pulmonary TB receiving anti-TB treatment.ResultsA total of 1452 adult patients newly diagnosed with pulmonary TB during the study period were identified and compared with 5808 matched patients. In the LAA cohort, 1258 received statin, and 295 received fibrate. Compared with patients who did not take LLA, patients who took oral LLAs had similar incidence of treatment completion at 9, 12, and 24 months.ConclusionsNeither statins nor fibrates provide clinical benefit superior to that achieved with standard anti-tuberculosis treatment. Future clinical trials should investigate the effects of statins and fibrates on short-course standard anti-TB therapy.

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— 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— 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.

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.

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.

// Hao Zhang 1,2,3 , Wan Lin 2 , Kalpana Kannan 4,5 , Liming Luo 4,5 , Jing Li 6 , Pei-Wen Chao 4,5 , Yan Wang 4,5 , Yu-Ping Chen 7 , Jiang Gu 6 , Laising Yen 4,5 1 Department of Integrative Oncology, Affiliated Cancer Hospital, Shantou University Medical College, Shantou, Guangdong, China. 2 Cancer Research Center, Shantou University Medical College, Shantou, Guangdong, China. 3 Tumor Tissue Bank, Affiliated Cancer Hospital, Shantou University Medical College, Shantou, Guangdong, China. 4 Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA. 5 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. 6 Department of Pathology, Shantou University Medical College, Shantou, Guangdong, China. 7 Department of Thoracic Surgery, Affiliated Cancer Hospital, Shantou University Medical College, Shantou, Guangdong, China. Correspondence: Hao Zhang, email: // Laising Yen, email: // Keywords : Transcriptome, transcription-induced chimeric RNAs, GOLM1-MAK10, secreted fusion protein, cancer biomarker, esophageal cancer. Received : October 7, 2013 Accepted : October 30, 2013 Published : November 1, 2013 Abstract It is increasingly recognized that chimeric RNAs may exert a novel layer of cellular complexity that contributes to oncogenesis and cancer progression, and could be utilized as molecular biomarkers and therapeutic targets. To date yet no fusion chimeric RNAs have been identified in esophageal cancer, the 6th most frequent cause of cancer death in the world. While analyzing the expression of 32 recurrent cancer chimeric RNAs in esophageal squamous cell carcinoma (ESCC) from patients and cancer cell lines, we identified GOLM1-MAK10 , as a highly cancer-enriched chimeric RNA in ESCC. In situ hybridization revealed that the expression of the chimera is largely restricted to cancer cells in patient tumors, and nearly undetectable in non-neoplastic esophageal tissue from normal subjects. The aberrant chimera closely correlated with histologic differentiation and lymph node metastasis. Furthermore, we demonstrate that chimera GOLM1-MAK10 encodes a secreted fusion protein. Mechanistic studies reveal that GOLM1-MAK10 is likely derived from transcription read-through/splicing rather than being generated from a fusion gene. Collectively, these findings provide novel insights into the molecular mechanism involved in ESCC and provide a novel potential target for future therapies. The secreted fusion protein translated from GOLM1-MAK10 could also serve as a unique protein signature detectable by standard non-invasive assays. These observations are critical as there is no clinically useful molecular signature available for detecting this deadly disease or monitoring the treatment response.

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.

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.

Objectives Intravenous patient-controlled analgesia (IVPCA) is often used to relieve pain after colorectal surgery. This study aimed to model the trajectory of analgesic demand over time after colorectal cancer surgery and explore potentially relevant influential factors using latent curve analysis, focusing on laparoscopic-assisted surgery and renal function. Materials and methods Patients receiving colorectal surgery with postoperative IVPCA were randomly divided into 2 equal parts to enable model construction and cross validation. Archived data were retrieved from the IVPCA pump. Latent curve modeling with 2 latent variables that reflected the baseline and slope of IVPCA demand trajectory over time was used and the effects of potentially influential factors on the 2 latent variables were evaluated. Goodness-of-fit indices were used to assess the model fit to both the model construction and validation data sets. Results Data were collected from 834 patients, of whom 112 had laparoscopic-assisted surgery. Latent curve analysis revealed that body weight increased the baseline analgesic demand over time, whereas increasing age, female sex, poor renal function, and laparoscopic-assisted surgery decrease it. By contrast, only age and weight exerted significant effects on the slope parameter to modify the trajectory of IVPCA demand. Patients with higher age or less weight tended to have a smoother decreasing trajectory of analgesic demands over time. There was good cross validation, as the parameter estimates derived from the model construction data set fitted well to the validation data set (root mean square error of approximation: 0.05). Conclusion Laparoscopic-assisted surgery and renal function affected the baseline trajectory of IVPCA demand over time, but had no significant effect on its shape.

To evaluate the association between daily morphine requirement and the intravenous patient-controlled analgesia (IVPCA) setting in patients undergoing spinal surgery.We conducted a retrospective analysis of 179 patients of American Society of Anesthesiologists physical status class I-III who underwent elective posterior lumbar spinal surgery and consented to IVPCA for postoperative pain control. The regi-mental solution contained morphine 1 mg/mL. The IVPCA program was set to deliver a priming dose of 1.5-4 mL, a basal infusion rate of 0-1.2 mL/hr, and a 0.5-1.5 mL bolus on demand with a 5-minute lockout interval. Demographic data, surgical procedures, analgesia program setting variables, 4-hour cumulative morphine dose and 11-point numeric rating scale for pain on postoperative days 1 and 2 were collected for comparison.The IVPCA requirement decreased gradually over time (p0.001). The number of vertebrae involved significantly influenced the daily morphine requirements (p = 0.01). None of the IVPCA settings, including continuous infusion, affected daily morphine requirements. On average, the analgesic requirement on postoperative day 2 was 18% less than that on postoperative day 1.The number of vertebrae involved was significantly associated with the daily IVPCA requirement. The IVPCA settings, including priming dose, basal infusion rate and bolus dose, did not affect the daily morphine requirements.

Although oral antidiabetic drugs (OADs) have been associated with immunomodulation in preclinical studies, little is still known about the association between the use of OADs and the risk of sepsis. Using a cohort of patients, extracted from Taiwan’s National Health Insurance Research Database, with type 2 diabetes who were newly diagnosed between 2010 and 2012 and treated with OADs, we conducted a nested case-control study involving 43,015 cases (patients who were first hospitalized for sepsis) and 43,015 matched controls. Compared with non-use, metformin use was associated with a decreased risk of developing sepsis (adjusted odds ratio [OR] 0.80, 95% confidence interval [CI] 0.77–0.83, P P

Objective.Pulmonary involvement is common in patients with systemic sclerosis (SSc), and this condition causes substantial morbidity and mortality. Disrupted immunity from the disease or associated medication may render such patients subject to tuberculosis (TB) infection. However, the relationship between SSc and TB has not yet been investigated.Methods.Using the Taiwan National Health Insurance Research Database, 838 patients with SSc diagnosed in Taiwan during 2000–2006 were identified and followed for emergence of TB infection. Incidence rate ratios (IRR) of TB compared to 8380 randomly selected age-, sex-, and comorbidity-matched controls without SSc were calculated. The Cox proportional hazards model was used for multivariate adjustment to identify independent risk factors for TB infection.Results.The risk of TB infection was higher in the SSc cohort than in controls (IRR 2.81, 95% CI 1.36–5.37; p = 0.004), particularly for pulmonary TB (IRR 2.53, 95% CI 1.08–5.30; p = 0.022). Other independent risk factors for TB infection in patients with SSc were age ≥ 60 years [hazard ratio (HR) 3.52, 95% CI 1.10–11.33; p = 0.035] and pulmonary hypertension (PH; HR 6.06, 95% CI 1.59–23.17; p = 0.008). Mortality did not differ for SSc patients with or without TB.Conclusion.In this nationwide study, the incidence of TB infection was significantly higher among patients with SSc than in controls without SSc. Special care should be taken in managing patients with SSc who are at high risk for TB, especially those aged ≥ 60 years or who also have PH.

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 0.001). The mortality rates of PLA were higher in the ESRD cohort than those in matched control cohort. Diabetes mellitus was an independent risk factor for mortality of PLA. Compared with non-ESRD patients, ESRD patients have a higher risk of PLA and poorer outcomes.

Previous studies have shown that nonsteroidal anti-inflammatory drug (NSAID) use might be associated with a lower risk of developing cancer in the general population. Patients on dialysis have increased risk for cancer, but there are no studies to determine the relationship between NSAID use and cancer risk in these patients. To identify any association between NSAID use and cancer risk in patients with end-stage renal disease on dialysis, we used Taiwan's National Health Insurance database to conduct a nationwide population-based, propensity score–matched cohort study. All cancers between groups were compared by Cox proportional hazards models. Compared to nonuse of NSAIDs, the use of non-COX-2-selective inhibitors (hazard ratio 0.81, 95% confidence interval 0.67–0.97) or COX-2-selective inhibitors (0.78, 0.62–0.98) was associated with a lower risk of developing cancer. NSAID use reduced the risk of respiratory (0.39, 0.19–0.79), breast (0.41, 0.19–0.89), kidney (0.58, 0.38–0.88), digestive tract (0.64, 0.49–0.85), and bladder cancers (0.73, 0.55–0.96). NSAID use, however, significantly increased risk for upper gastrointestinal bleeding (odds ratio, 1.15, 1.07–1.23) but not adverse cardiac or cerebrovascular events. Thus, NSAID use was associated with a lower risk of developing cancer in chronic dialysis patients; however, they should still be used with caution due to the side effects of gastrointestinal bleeding.