Real-World Usage of Sacubitril/Valsartan in Korea: A Multi-Center, Retrospective Study.

Background and Objectives: Differences in drug prescriptions exist between clinical trials and real-world practice. We evaluated the real-world treatment patterns of sacubitril/valsartan in Korean patients with heart failure (HF). Methods: In this retrospective, multicenter cohort study, 600 patients with HF with reduced left-ventricular ejection fraction (LVEF <40%) with ≥1 sacubitril/valsartan prescription were identified by reviewing patient-level medical records at six academic tertiary hospitals in Korea between February 2017 and April 2019. Results: At baseline, 59.2%, 28.3%, 4.8%, and 7.7% of the patients received low (50 mg bid), moderate (100 mg bid), target (200 mg bid), and unconventional dose of sacubitril/valsartan, respectively. Patients with low and moderate doses experienced either 'no-titration' (39.8%) or 'stable up-titration' (41.5%). At 12 months, 31.7%, 28.5%, 24.8%, and 15% received low, moderate, target doses, and unconventional dose, respectively. On follow-up, 31 (5.2%) patients discontinued sacubitril/valsartan. The time-averaged N-terminal pro-B-type natriuretic peptide (NT-proBNP) level decreased from 879.6 to 406 pg/mL (ratio, 0.5; 95% confidence interval, 0.4-0.5). The mean LVEF increased by 10.4±12.2% from 27.2±5.8 to 36.3±11.1%, whereas LV end-diastolic volume index decreased by 18.7±26.1 mL/m2 from 114.5±37.7 mL/m2 to 98.9±42.3 mL/m2 at baseline and follow-up, respectively. Conclusions: In real-world practice, 95% patients started with low and moderate doses of sacubitril/valsartan. Many patients experienced dose up-titration during follow-up; 30% reached the target dose. Cardiac reverse remodelling was reflected by a profound NT-proBNP level and LV size reduction, and LVEF increment. This study confirms the gap in treatment patterns between clinical trials and real-world practice.

Chinese Herbal Medicine Decreases Incidence of Cirrhosis in Patients with Non-Alcoholic Fatty Liver Disease in Taiwan: A Propensity Score-Matched Cohort Study.

Objective: Chinese herbal medicine (CHM) is quite popular in Asia. The purpose of this study is to investigate the benefits of decreasing the risk of cirrhosis in patients with non-alcoholic fatty liver disease (NAFLD) by using CHM. Design: We performed a 1:3 propensity score-matched cohort study to analyze patients with NAFLD diagnosed between January 1, 1997 and December 31, 2011 through the Taiwanese National Health Insurance Research Database. Patients who received CHM therapy from the initial date of diagnosis of NAFLD to December 31, 2011 were included in the CHM group. Patients who were not treated with CHM during the same interval were categorized in the non-CHM group. Cox regression model was used to adjust for sex, age, comorbidities, and drug use. Hazard ratios were also compared between the two groups. Results: A total of 13,072 patients were identified after 1:3 propensity score matching. The patients had similar basic characteristics. A lower cumulative incidence of cirrhosis was found in the CHM cohort (log-rank test, p < 0.0001). Finally, 176 patients in the CHM cohort (4.66 per 1000 person-years) and 582 patients in the non-CHM cohort (7.92 per 1000 person-years) developed cirrhosis (adjusted hazard ratios 0.63, 95% confidence interval 0.53-0.75). The effect of CHM to lower cirrhosis incidence was independent of sex, drug use, and comorbidities, including diabetes mellitus, hypertension, and cardiovascular diseases. Patients older than 40 years of age and without comorbidities such as chronic obstructive pulmonary disease, hyperlipidemia, alcoholism, tobacco use, or obesity also benefited from CHM. Conclusions: Our study is the first large-scale investigation in Taiwan that shows the association between patients with NAFLD and cirrhosis prevention after CHM intervention. The results may be useful for treatment and for decision making for patients and clinical doctors. Further restricted trials are needed to support our findings.

Atrial and Ventricular Response to Treatment of Premature Ventricular Complexes.

BACKGROUND: Premature ventricular complexes (PVC) may cause ventricular dyssynchrony and lead to left atrium and ventricle mechanical abnormalities. Although ventricular cardiomyopathy due to PVCs has been well studied, little is known about atrial adaptation to PVCs. OBJECTIVES: To assess atrial and ventricular responses to PVC therapy. METHODS: All patients with PVC burden > 5000 beats/day on Holter monitoring were enrolled. Baseline demographics, comorbidities, social habits, Holter parameters, and echocardiography profiles were recorded. Follow-up Holter electrocardiography (ECG) and echocardiography data were compared between PVC-treated and non-treated patients. RESULTS: Two hundred and eighty-six patients were enrolled, of whom 139 received PVC treatment. Among the treated patients, 125 who underwent follow up Holter ECG or echocardiography were included in the final analysis. The mean follow-up times of Holter ECG and echocardiography were 9.40 ± 6.70 and 9.40 ± 5.52 months, respectively. Ventricular arrhythmic burden was significantly reduced in the treatment group (16.46% vs. 13.41%, p = 0.041) but was significantly increased in the observation group (7.58% vs. 14.95%, p = 0.032). A significant increase in left atrial (LA) diameter (36.94 mm vs. 39.46 mm, p = 0.025) and reduction in left ventricular ejection fraction (LVEF) (57.26% vs. 53.8%, p = 0.040) were noted in the observation group. There were no significant differences in supraventricular arrhythmic burden in the observation group and LA diameter and LVEF in the treatment group. CONCLUSIONS: PVC therapy effectively reduced ventricular arrhythmic burden in the treatment group on follow-up. Our data suggest that PVC treatment may prevent LA dilation and LVEF decline.

Increased risk of perforated appendicitis in patients with schizophrenia and dementia: A population-based case-control study.

Previous studies have suggested that patients with psychotic or mental disorders are relatively pain insensitive, resulting in difficulties in the diagnosis of acute intra-abdominal diseases requiring emergency surgeries. We aimed to evaluate whether central nervous system (CNS) or mental disorders are associated with perforated appendicitis in patients with acute appendicitis.We conducted a population-based case-control study using Taiwan's National Health Insurance Research database. Patients aged >18 years who had been hospitalized with a diagnosis of acute appendicitis between 2000 and 2013 were identified. After 1:1 matching for age and sex, 2792 patients with perforated appendicitis (case group) and 2792 patients with nonperforated appendicitis (control group) were included. CNS disorders, mental disorders, pain control medication, and several comorbidities were analyzed for the odds of appendiceal perforation with 95% confidence interval (CI) using the multivariable logistic regression model.Schizophrenia and dementia were associated with a high risk of appendiceal rupture in patients with acute appendicitis, with an adjusted odds ratio of 2.01 for dementia (95% CI: 1.19-3.39, P = .009) and 4.8 for schizophrenia (95% CI: 1.62-14.19, P = .005). Other factors, such as other CNS disorders, comorbidities, and pain control medication, were not associated with the risk of perforated appendicitis.Dementia and schizophrenia are associated with perforated appendicitis in patients with acute appendicitis. This might be owing to altered pain perception, difficult symptom expression, and delayed hospitalization. Further studies are still needed to determine the underlying mechanism and confirm the causality.

Pioglitazone Exposure Reduced the Risk of All-Cause Mortality in Insulin-Treated Patients with Type 2 Diabetes Mellitus.

CONTEXT: The long-term safety and benefit of pioglitazone use in combination with insulin are still uncertain. OBJECTIVE: This study compared the risks of all-cause mortality and major cardiovascular (CV) events between pioglitazone users and nonusers receiving insulin therapy. DESIGN, SETTING AND PATIENTS: We conducted a 13-year retrospective cohort study by using data from the population-based National Health Insurance Research Database in Taiwan. A total of 20 376 patients with type 2 diabetes mellitus (T2DM) receiving insulin therapy were enrolled during 2000 to 2012. Overall, the incidence rates of all-cause mortality and CV events were compared between 2579 pioglitazone users and 2579 matched nonusers. RESULTS: After adjustment for age, sex, comorbidities, Diabetes Complications Severity Index scores, and drugs used, mortality rates were 30.26 and 15.02 per 1000 person-years for pioglitazone nonusers and users, respectively. The adjusted hazard ratio (aHR) of mortality was 0.47 (95% confidence interval [CI]: 0.38-0.58, P < 0.001) for pioglitazone users compared with nonusers. The aHRs of CV and non-CV deaths were 0.78 (95% CI: 0.51-1.19) and 0.50 (95% CI: 0.38-0.66), respectively. The aHRs of hospitalized coronary artery disease, hospitalized stroke, and incident heart failure were not significantly different between pioglitazone users and nonusers. CONCLUSIONS: This nationwide cohort study demonstrated that pioglitazone use reduced the risks of all-cause mortality and non-CV death for patients with T2DM undergoing insulin therapy.

Association between abdominal hernia and the risk of subsequent dementia.

OBJECTIVE: Matrix metalloproteinases (MMPs) may play a role in the pathophysiology of neurodegenerative disease and hernia formation. This retrospective cohort study was designed to assess whether there is an association between hernia and the risk of dementia. MATERIALS AND METHODS: Patients (≥45 years) with hernias were identified between 2000 and 2008 from a longitudinal claims data of one million beneficiaries from Taiwan's National Health Insurance program. A control group of patients with comparable distributions of sex, age, socioeconomic status, urbanization, and medical comorbidities without hernia were chosen for matching in a ratio of 1:1. Patients previously diagnosed with dementia were excluded. Follow-up ended on December 31, 2013. Incidence rate of dementia was compared between patients with hernias and those without. Cox proportional hazards models were used to estimate hazards relative to those of the control group. RESULTS: After matching, there were 4,784 hernia and 4,784 nonhernia patients. Hernia patients showed a higher incidence rate and hazard ratio of dementia than those in nonhernia group (8.82 vs. 7.19/1,000 person-years; adjusted hazard ratio [aHR], 1.24; 95% CI, 1.07 to 1.45; p < .01). Advanced age (p < .0001), hypertension (p = .0139), head injury (p = .0003), and stroke (p = .041) were found to be risk factors for dementia, while patients with high socioeconomic status (p < .01) and history of coronary artery disease (p = .0292) were unlikely to develop dementia in our cohort study. CONCLUSION: Patients with hernias were associated with a higher incidence of dementia than those without. Our finding should be validated in further prospective studies with larger samples.

Risk of Endometriosis and Subsequent Ovary and Breast Cancers in Nurses: A Population-Based Cohort Study in Taiwan.

BACKGROUND: Endometriosis has been associated with the subsequent development of ovarian and breast cancers. This study evaluated whether nurses were at increased risks of developing endometriosis and subsequent ovarian and breast cancers. METHODS: From Taiwan National Health Insurance Research Database during 2000 to 2011, we established 3 study cohorts, consisting of 23,801 nurses, 11,973 other hospital employees, and 143,096 general women free of endometriosis and cancer. Women in all cohorts were followed to the end of 2011 to measure the occurrences of endometriosis and subsequent ovarian and breast cancers. The incident endometriosis cases and related hazard ratio (HR) and 95% confidence interval (CI) were calculated. The incident cases of ovarian cancer and breast cancer and related odds ratio were calculated. RESULTS: The incidence of endometriosis was the highest in the nurse cohort (4.23 per 100, n = 966) followed by other health professionals (3.74 per 100, n = 427) and control cohort (3.06 per 100, n = 4193), with adjusted hazard ratios of 1.28 (95% CI = 1.20-1.38) and 1.13 (95% CI = 1.02-1.25), respectively, comparing to controls. Among those who developed endometriosis, nurses had higher subsequent ovarian cancer and lower breast cancer, but not significant. CONCLUSIONS: Nurses are at a higher risk of developing endometriosis. However, the link between endometriosis and subsequent cancers is weak.

Establishment and validation of a prediction model for ischemic stroke risks in patients with type 2 diabetes.

AIMS: A risk scoring system for predicting ischemic stroke incidence may identify type 2 diabetes patients at high risk for ischemic stroke who can benefit from preventive intervention programs. Such a risk scoring system can serve as a benchmark to test novel putative risk factors. METHODS: The study adopted a retrospective cohort, including 28,124 Chinese patients with type 2 diabetes aged 30-84 years during 2001-2004. Participants were randomly assigned to the derivation and validation sets at a 2:1 ratio. Cox's proportional hazard regression model was used to identify risk factors of ischemic stroke incidence in the derivation set. And then the steps proposed by the Framingham Heart Study for establishing an ischemic stroke prediction model with a scoring system was used. RESULTS: Among 9374 patients in the validation set, 1076 subjects (11.48%) developed ischemic stroke with a mean follow up period of 8.0 years. We identified the following risk factors: age, gender, smoking habit, duration of type 2 diabetes, blood pressure, HbA1c level, total cholesterol to high-density lipoprotein ratio, creatinine, fasting plasma glucose variation (FPG-CV), arterial embolism and thrombosis, diabetes retinopathy, hypoglycemia, anti-diabetes medication use, and cardiovascular medication. The area under receiver operating characteristic curve of the 3-year, 5-year, and 8-year ischemic stroke incidence risks were 0.72, 0.71, and 0.68 for the validation set, respectively. CONCLUSIONS: This proposed ischemic stroke incidence risk prediction model is the first model established for Chinese patients with type 2 diabetes recruited from nationwide clinical settings.