Yung Tai Chen

Long-Term Clinical Outcome of Major Adverse Cardiac Events in Survivors of Infective Endocarditis A Nationwide Population-Based Study

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.

Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus

BACKGROUNDnRecent studies concluded that dipeptidyl peptidase-4 (DPP-4) inhibitors provide glycemic control but also raised concerns about the risk for heart failure in patients with type 2 diabetes mellitus (T2DM). However, large-scale studies of the effects on cardiovascular outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy remain scarce.nnnOBJECTIVEnTo compare clinical outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy in patients with T2DM.nnnDESIGNnNationwide study using Taiwans National Health Insurance Research Database.nnnSETTINGnTaiwan.nnnPATIENTSnAll patients with T2DM aged 20 years or older between 2009 and 2012. A total of 10,089 propensity score-matched pairs of DPP-4 inhibitor users and sulfonylurea users were examined.nnnMEASUREMENTSnCox models with exposure to sulfonylureas and DPP-4 inhibitors included as time-varying covariates were used to compare outcomes. The following outcomes were considered: all-cause mortality, major adverse cardiovascular events (MACEs) (including ischemic stroke and myocardial infarction), hospitalization for heart failure, and hypoglycemia. Patients were followed until death or 31 December 2013.nnnRESULTSnDPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure.nnnLIMITATIONnObservational study design.nnnCONCLUSIONnCompared with sulfonylureas, DPP-4 inhibitors were associated with lower risks for all-cause death, MACEs, ischemic stroke, and hypoglycemia when used as add-ons to metformin therapy.nnnPRIMARY FUNDING SOURCEnNone.

Association of Postdischarge Rehabilitation with Mortality in Intensive Care Unit Survivors of Sepsis

RATIONALEnIntensive care unit (ICU)-acquired weakness is a common issue for sepsis survivors that is characterized by impaired muscle strength and causes functional disability. Although inpatient rehabilitation has not been found to reduce in-hospital mortality, the impact of postdischarge rehabilitation on sepsis survivors is uncertain.nnnOBJECTIVESnTo investigate the benefit of postdischarge rehabilitation to long-term mortality in sepsis survivors.nnnMETHODSnWe conducted a nationwide, population-based, high-dimensional propensity score-matched cohort study using Taiwans National Health Insurance Research Database. The rehabilitation cohort comprised 15,535 ICU patients who survived sepsis and received rehabilitation within 3 months after discharge between 2000 and 2010. The control cohort consisted of 15,535 high-dimensional propensity score-matched subjects who did not receive rehabilitation within 3 months after discharge. The endpoint was mortality during the 10-year follow-up period.nnnMEASUREMENTS AND MAIN RESULTSnCompared with the control cohort, the rehabilitation cohort had a significantly lower risk of 10-year mortality (adjusted hazard ratio, 0.94; 95% confidence interval, 0.92-0.97; P < 0.001), with an absolute risk reduction of 1.4 per 100 person-years. The frequency of rehabilitation was inversely associated with 10-year mortality (≥3 vs. 1 course: adjusted hazard ratio, 0.82; P < 0.001). Compared with the control cohort, improved survival was observed in the rehabilitation cohort among ill patients who had more comorbidities, required more prolonged mechanical ventilation, and had longer ICU or hospital stays, but not among those with the opposite conditions (i.e., less ill patients).nnnCONCLUSIONSnPostdischarge rehabilitation may be associated with a reduced risk of 10-year mortality in the subset of patients with particularly long ICU courses.

Long-Term Mortality and Major Adverse Cardiovascular Events in Sepsis Survivors. A Nationwide Population-based Study

RATIONALEnPatients 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.nnnOBJECTIVESnOur study aimed to investigate the long-term clinical outcomes in sepsis survivors.nnnMETHODSnIn this nationwide population-based study, data from patients with sepsis were retrieved from Taiwans 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.nnnMEASUREMENTS AND MAIN RESULTSnCompared with matched population control subjects, sepsis survivors had higher risks of all-cause mortality (hazard ratio [HR], 2.18; 95% confidence interval [CI], 2.14-2.22), major adverse cardiovascular events (HR, 1.37; 95% CI, 1.34-1.41), ischemic stroke (HR, 1.27; 95% CI, 1.23-1.32), hemorrhagic stroke (HR, 1.36; 95% CI, 1.26-1.46), myocardial infarction (HR, 1.22; 95% CI, 1.14-1.30), heart failure (HR, 1.48; 95% CI, 1.43-1.53), and sudden cardiac death or ventricular arrhythmia (HR, 1.65; 95% CI, 1.57-1.74). Similar results, although slightly attenuated risks, were found when comparisons were made with hospitalized control subjects without sepsis.nnnCONCLUSIONSnThese data indicate that sepsis survivors had substantially increased risks of subsequent all-cause mortality and major adverse cardiovascular events at 1 year after discharge, which persisted for up to 5 years after discharge.

Association of prior antiplatelet agents with mortality in sepsis patients: a nationwide population-based cohort study

AbstractBackgroundAntiplatelet agents are widely used for cardiovascular diseanses, but their pleiotropic effects in sepsis are controversial.ObjectiveTo investigate the association between antiplatelet agents and the survival benefit for sepsis patients.DesignA nationwide population-based cohort and nested case–control study.SettingTaiwan National Health Insurance database.ParticipantsAll patients (age ≥18xa0years) who were hospitalized for sepsis between January 2000 and December 2010.MeasurementsConditional logistic regression was used to adjust for confounding. Adjusted odd ratios (ORs) were used to compare the mortality rate due to sepsis in antiplatelet drug users and nonusers.ResultsOf 683,421 included patients, 229,792 (33.6xa0%) patients died during hospitalization for sepsis, and the rest (64.4xa0%) survived to discharge. Use of antiplatelet agents before admission was associated with a lower risk of mortality in sepsis patients (aOR 0.82, 95xa0% confidence interval [CI] 0.81–0.83, Pxa0<xa00.001). By using another case–control study design, the beneficial effect was more significant in current users (aOR 0.78, 95xa0% CI 0.76–0.79) than in recent users (aOR 0.88, 95xa0% CI 0.85–0.91), but was not significant in past users (aOR 1.00, 95xa0% CI 0.98–1.02).LimitationsObservational study.ConclusionsPrior use of antiplatelet agents was associated with a survival benefit in sepsis patients.

Effect of the use of low and high potency statins and sepsis outcomes

AbstractIntroductionnAlthough statins have been shown to have cholesterol-lowering effects, their pleiotropic benefits on sepsis remain a matter of debate. In addition, the influence of statin potency on sepsis-related mortality has never been explored. The aim of our study was to determine the sepsis outcomes of low- and high-potency statin users and non-users.nMethodsThis nationwide, population-based, propensity score-matched analysis used data from the linked administrative databases of Taiwan’s National Health Insurance program. Patients were hospitalized for sepsis between 2000 and 2010. All-cause mortality and major adverse consequences of sepsis, such as in-hospital death, intensive care unit admission, shock events, and the use of mechanical ventilation, were assessed. Patients were divided into high-potency statin users (at least 10xa0mg rosuvastatin, at least 20xa0mg atorvastatin, or at least 40xa0mg simvastatin), low-potency statin users (all other statin treatments), and non-users.ResultsA propensity score-matched cohort of 27,792 statin users and 27,792 non-users was included. Of 27,792 statin users, 9,785 (35.2xa0%) were treated with high-potency statins and 18,007 (64.8xa0%) were treated with low-potency statins. The 1-year mortality risk was significantly lower among both low-potency [adjusted hazard ratio (aHR) 0.89, 95xa0% confidence interval (CI) 0.85–0.93] and high-potency (aHR 0.80, 95xa0% CI 0.75–0.86) statin users compared with non-users. The risks of mortality and adverse consequences of sepsis were lower among high-potency than among low-potency statin users.ConclusionsHigh-potency statin use is associated with a lower risk of sepsis-related mortality compared with low-potency statin use.

Nonsteroidal anti-inflammatory drug use is associated with cancer risk reduction in chronic dialysis patients

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 Taiwans 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.

Mesenteric ischemia in patients with end-stage renal disease: A nationwide longitudinal study

Background and Aims: Mesenteric ischemia is an uncommon disorder associated with an extremely high mortality rate. Only limited studies have evaluated this lethal disease among patients with end-stage renal disease (ESRD). The objective of this study was to evaluate the risks of mesenteric ischemia among ESRD patients and compare the incidence between two dialysis modalities. Methods: Records of all ESRD patients older than 20 years of age from 1998 to 2007 and a control group consisting of 1 million records were retrieved from the Taiwan National Health Insurance Research Database. Hospitalizations for mesenteric ischemic events were retrieved using ICD-9-CM diagnosis codes and ICD-9-CM operation codes from inpatient claims. Results: Among 55,807 incident ESRD patients who received hemodialysis or peritoneal dialysis, there were 458 mesenteric ischemic events, corresponding to an incidence rate of 2.7 per 1,000 patient-years. Multivariate Cox regression analysis indicated that the independent risk factors were old age (HR 1.42 per 10 years), diabetes (HR 2.85), peripheral vascular disease (HR 2.66), atrial fibrillation (HR 2.15), heart failure (HR 1.65), chronic pulmonary disease (HR 1.41), neoplasm (HR 1.54), peptic ulcer disease (HR 1.86), and peritoneal dialysis (HR 1.51, all p < 0.05). There was no effect of dialysis modality on the mesenteric ischemia mortality rate. Conclusion: The risk of mesenteric ischemia for ESRD patients was 44.1 (95% confidence interval 13.4–106.2, p < 0.001) times higher than that of the general population. Compared to hemodialysis, peritoneal dialysis was associated with a higher risk of mesenteric ischemia.

Migraine and incidence of ischemic stroke: A nationwide population-based study

Background The association between migraine and the incidence of ischemic stroke varies in different subgroups of patients. We aimed to clarify this association using a population-based database. Method A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Two cohorts were extracted: a neurologist-diagnosed migraine cohort, and a non-headache, propensity score-matched comparison cohort. All participants were enrolled in this study between 2005 and 2009, and were followed through the end of 2010, death, or the occurrence of ischemic stroke. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated with a Cox proportional hazards model to compare the between-group risks. Results Both cohorts (nu2009=u2009119,017 each) were followed for a mean period of 3.6u2009±u20091.3 years. A total of 744 migraine patients (429,741 person-years) and 617 matched comparison individuals (436,141 person-years) developed ischemic stroke during the research period. Compared to the comparison cohort, patients with migraine were at an increased risk of ischemic stroke (aHR: 1.24, 95% CI: 1.12–1.38, pu2009<u20090.001). Subgroup analysis by age and sex revealed the highest risk in women agedu2009≤u200945 years (aHR: 3.44, 95% CI: 2.20–5.39, pu2009<u20090.001), especially among those with migraine with aura (aHR: 4.58, 95% CI: 2.45 – 8.56, pu2009<u20090.001). A trend for increased stroke risk was observed in men agedu2009≤u200945 years (aHR: 1.54, 95% CI: 0.96–2.48, pu2009=u20090.075). Conclusion Migraine is associated with an increased risk of ischemic stroke, especially in younger (ageu2009≤u200945 years) women with migraine with aura. The trend toward ischemic stroke in younger men merits further exploration.

Cluster headache is associated with an increased risk of depression: A nationwide population-based cohort study:

Objective To investigate whether cluster headache (CH) was a risk factor for depression in a nationwide population-based follow-up study. Background There are few studies about the relationship between CH and depression, and prior research has been limited by cross-sectional studies or small sample sizes. Methods We identified 673 CH patients from the Taiwan National Health Insurance database between 2005 and 2009. The two comparison cohorts included age-, sex- and Charlson’s score-matched migraine patients (nu2009=u20092692) and controls (patients free from migraine or CH, nu2009=u20092692). The cumulative incidence of depression was compared among these three cohorts until the end of 2009. We also calculated predictors of depression in the CH cohort. Results After the median 2.5-year follow-up duration, the CH cohort had a greater risk for developing depression compared to the control cohort (adjusted hazard ratio; aHRu2009=u20095.6, 95% CI 3.0–10.6, pu2009<u20090.001) but not the migraine cohort (aHRu2009=u20091.1, 95% CI 0.7–1.7, pu2009=u20090.77). Of the CH patients, the number of cluster bout periods per year was a risk factor for depression (aHRu2009=u20093.8, 95% CI 2.6–5.4, pu2009<u20090.001). Conclusion Our results showed that CH is associated with an increased risk for depression. The strength of this association is similar to that of migraine.