Use of nicorandil is associated with increased risk of incident atrial fibrillation.

BACKGROUND: Nicorandil will activate ATP-sensitive potassium channel (KATP). However, activation of potassium channels plays an important role in the mechanism of atrial fibrillation (AF) or atrial flutter (AFL). Whether use of nicorandil might contribute to initiation and/or perpetuation of AF/AFL remained unknown. We determined the relationship between use of nicorandil and risk of atrial fibrillation and determined its molecular mechanism. METHODS: We performed a nested case-control study using a cohort from the National Health Insurance Research Database (NHIRD) of Taiwan. The association between nicorandil use and risk of atrial fibrillation/flutter was estimated by logistic regression model. We also performed molecular, cellular and animal studies to explain the association. RESULTS: A total of 715 individuals who experienced AF/atrial flutter were matched to 72,215 controls. New use of nicorandil was found to be associated with increased risk for AF/AFL (odds ratio [OR], 2.34; 95% CI 1.07-5.13) compared to nitrate use. We found the expression of KATP subunits Kir6.2 and SUR2A in human and rat left atrial tissues. Furthermore, nicorandil directly shortened action potential duration (APD) in rat left atrium and shortened the QT interval of cultured human induced pluripotent stem cell (iPSC) derived cardiomyocytes (iPSC-CMs). CONCLUSIONS: Use of nicorandil was found to be associated with increased risk of AF/AFL. We also showed the expression of KATP subunits in human atria, and a possible mechanism that use of nicorandil increases the risk of AF through activation of KATP and shortening of atrial APD.

Incidence and predictors of idiopathic pneumonia syndrome in hematopoietic stem cell transplant patients: a nationwide registry study.

Idiopathic pneumonia syndrome (IPS) is a rare but deadly complication of hematopoietic stem cell transplantation (HSCT). This study characterized the incidence and risk factors for IPS after HSCT in Taiwan. Data from January 2009 to February 2019 was collected from the Taiwan Society of BMT national registry. Forty-three (1.1%) of 3924 HSCT patients who developed IPS were identified. Incidence of IPS was lower in patients who received autologous HSCT than patients who received allogeneic HSCT (0.68% vs 1.44%, P = 0.022). Multivariate analysis showed that use of TBI and intravenous busulfan in the conditioning regimen were each independent predictor of IPS after HSCT. In addition, development of IPS was significantly associated with increased risk of death in the first 120 days post-HSCT (HR, 2.09; 95% CI, 1.08 to 4.05, P = 0.029) and 2 years post-HSCT (HR, 1.65; 95% CI, 1.07 to 2.542, P = 0.023), but not beyond 2 years post-HSCT. However, survival outcomes did not differ significantly between patients with IPS who received autologous versus allogeneic HSCT (P = 0.52). In conclusion, despite the relatively low incidence of post-HSCT IPS in Taiwan, mortality remains high. The results of this study will help to identify high-risk patients for early intervention and guide future therapeutic research.

Association Between Aspirin Use and Sepsis Outcomes: A National Cohort Study.

BACKGROUND: Aspirin has anti-inflammatory and antiplatelet activities and directly inhibits bacterial growth. These effects of aspirin may improve survival in patients with sepsis. We retrospectively reviewed a large national health database to test the relationship between prehospital aspirin use and sepsis outcomes. METHODS: We conducted a retrospective population-based cohort study using the National Health Insurance Research Database of Taiwan from 2001 to 2011 to examine the relationship between aspirin use before hospital admission and sepsis outcomes. The association between aspirin use and 90-day mortality in sepsis patients was determined using logistic regression models and weighting patients by the inverse probability of treatment weighting (IPTW) with the propensity score. Kaplan-Meier survival curves for each IPTW cohort were plotted for 90-day mortality. For sensitivity analyses, restricted mean survival times (RMSTs) were calculated based on Kaplan-Meier curves with 3-way IPTW analysis comparing current use, past use, and nonuse. RESULTS: Of 52,982 patients with sepsis, 12,776 took aspirin before hospital admission (users), while 39,081 did not take any antiplatelet agents including aspirin before hospital admission (nonusers). After IPTW analysis, we found that when compared to nonusers, patients who were taking aspirin within 90 days before sepsis onset had a lower 90-day mortality rate (IPTW odds ratio [OR], 0.90; 95% confidence interval [CI], 0.88-0.93; P < .0001). Based on IPTW RMST analysis, nonusers had an average survival of 71.75 days, while current aspirin users had an average survival of 73.12 days. The difference in mean survival time was 1.37 days (95% CI, 0.50-2.24; P = .002). CONCLUSIONS: Aspirin therapy before hospital admission is associated with a reduced 90-day mortality in sepsis patients.

In-hospital Cardiac Arrest in Patients With Sepsis: A National Cohort Study.

Background: Little is known about the risk of in-hospital cardiac arrest (IHCA) among patients with sepsis. We aimed to characterize the incidence and outcome of IHCA among patients with sepsis in a national database. We then determined the major risk factors associated with IHCA among sepsis patients. Methods: We used data from a population-based cohort study based on the National Health Insurance Research Database of Taiwan (NHRID) between 2000 and 2013. We used Martin's implementation that combined the explicit ICD-9 CM codes for sepsis and six major organ dysfunction categories. IHCA among sepsis patients was identified by the presence of cardiopulmonary resuscitation procedures. The survival impact was analyzed with the Cox proportional-hazards model using inverse probability of treatment weighting (IPTW). The risk factors were identified by logistic regression models with 10-fold cross-validation, adjusting for competing risks. Results: We identified a total of 20,022 patients with sepsis, among whom 2,168 developed in-hospital cardiac arrest. Sepsis patients with a higher burden of comorbidities and organ dysfunction were more likely to develop in-hospital cardiac arrest. Acute respiratory failure, hematological dysfunction, renal dysfunction, and hepatic dysfunction were associated with increased risk of IHCA. Regarding the source of infection, patients with respiratory tract infections were at the highest risk, whereas patients with urinary tract infections and primary bacteremia were less likely to develop IHCA. The risk of IHCA correlated well with age and revised cardiac risk index (RCRI). The final competing risk model concluded that acute respiratory failure, male gender, and diabetes are the three strongest predictors for IHCA. The effect of IHCA on survival can last 1 year after hospital discharge, with an IPTW-weighted hazard ratio of 5.19 (95% CI: 5.06, 5.35) compared to patients who did not develop IHCA. Conclusion: IHCA in sepsis patients had a negative effect on both short- and long-term survival. The risk of IHCA among hospitalized sepsis patients was strongly correlated with age and cardiac risk index. The three identified risk factors can help clinicians to identify patients at higher risk for IHCA.

Risk of out-of-hospital cardiac arrest among sepsis survivors in Taiwan: analysis of a nationwide population-based cohort.

OBJECTIVES: There is minimal literature examining the association of sepsis with out-of-hospital cardiac arrest (OHCA). Using a large national database, we aimed to quantify the risk of OHCA among sepsis patients after hospital discharge. DESIGN: Population-based cohort study. SETTING: Nationwide sepsis cohort retrieved from the National Health Insurance Research Database of Taiwan between 2000 and 2013. PARTICIPANTS: We included 17 304 patients with sepsis. After hospital discharge, 144 patients developed OHCA within 30 days and 640 between days 31 and 365. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcomes were OHCA events following hospital discharge for sepsis. To evaluate the independent association between sepsis and OHCA after a sepsis hospitalisation, we constructed two non-sepsis comparison cohorts using risk set sampling and propensity score matching techniques (non-infection cohort, non-sepsis infection cohort). We plotted the daily number and daily risk of OHCA within 1 year of hospital discharge between sepsis and matched non-sepsis cohorts. We used Cox regression to evaluate the risk of early and late OHCA, comparing sepsis to non-sepsis patients. RESULTS: Compared with non-infected patients, sepsis patients had a higher rate of early (HR 1.66, 95% CI: 1.27 to 2.16) and late (HR 1.19, 95% CI: 1.06 to 1.33) OHCA events. This association was independent of age, sex or cardiovascular history. Compared with non-sepsis patients with infections, sepsis patients had a higher rate of both early (HR 1.28, 95% CI: 1.00 to 1.63) and late (HR 1.13, 95% CI: 1.01 to 1.27) OHCA events, especially among patients with cardiovascular disease (OR 1.35, 95% CI: 1.01 to 1.81). CONCLUSIONS: Sepsis patients had increased risk of OHCA compared with matched non-sepsis controls, which lasted up to 1 year after hospital discharge.

The Effect of Efavirenz on Estradiol Metabolism in Transgender Women.

The goal of hormonal therapy in treating gender dysphoria is to maintain cross-sex hormone levels in the normal physiological range for the desired gender. Estrogen is the mainstay of hormonal therapy for male to female transgender patients. Efavirenz, a non-nucleoside reverse-transcriptase inhibitor, has been one of the most commonly prescribed antiretroviral therapies (ARTs). However, this regimen has also given rise to the most clinically significant drug-drug interactions between ARTs and hormone-based contraceptives. We discuss here three transgender HIV-positive women in whom efavirenz effected the metabolism of orally administered estradiol (and probably medroxyprogesterone).