Diabetes, Hypertension and Cardiovascular Disease: Clinical Insights, Mechanisms and Pharmacotherapies.

Cardiovascular disease (CVD) is a serious issue demanding world attention, not only because of its role in increased mortality, but also in conjunction with the aging population and growing prevalence of other co-morbidities, such as hypertension, diabetes, etc [...].

Ticagrelor versus Adjusted-Dose Prasugrel in Acute Coronary Syndrome with Percutaneous Coronary Intervention.

Dual antiplatelet therapy (DAPT) with ticagrelor or adjusted-dose prasugrel has been used for acute coronary syndrome (ACS). However, few studies have directly compared these two drugs. In this study, we compared the real-world applications and outcomes of these two drugs in patients with ACS who had undergone percutaneous coronary intervention (PCI). This retrospective cohort study was conducted using the data of eligible patients with ACS who had undergone PCI at Chang Gung Memorial Hospital System between June 2019 and December 2021. The primary efficacy-related outcome was the occurrence of major adverse cardiovascular events (MACEs), and the primary safety-related outcome was major bleeding. Inverse probability of treatment weighting based on propensity score was performed to reduce confounding effects. The study included 2,636 patients; of them, 429 received prasugrel and 2,207 received ticagrelor. No significant between-group difference was observed in the risk of MACE (13.1 vs. 13.1 events per 100 person-years, respectively, hazard ratio (HR): 1.01, 95% confidence interval (CI): 0.71-1.43). Both groups exhibited similar rates of major bleeding (3.9 vs. 4.1 events per 100 person-years, respectively, subdistribution HR: 0.96, 95% CI: 0.68-1.35). In real-world settings, adjusted-dose prasugrel and ticagrelor exhibit comparable safety and efficacy profiles in East Asian patients with ACS after PCI. Our findings offer valuable insights for future clinical decision making and patient management strategies.

Evaluating the applicability of ivabradine in acute heart failure.

BACKGROUND: While ivabradine has demonstrated benefits in heart rate control and prognosis for chronic heart failure patients, its application in acute decompensated heart failure remains underexplored. HYPOTHESIS: For patients with acute decompensated heart failure with reduced ejection fraction (HFrEF) who are intolerant to ß-blockers or unable to further titrate their dosage, the use of ivabradine is hypothesized to be effective and safe is improving outcomes. METHODS: This retrospective, multicenter database analysis included patients with hospitalized decompensated heart failure with a left ventricular ejection fraction of ≤40% from June 1, 2015 to December 31, 2020. The exclusion criteria were a baseline heart rate of <70 bpm, previous use of ivabradine, mortality during admission, existing atrial fibrillation, or atrial flutter. The primary outcome was the composite of cardiovascular death and hospitalization for heart failure. RESULTS: Of the 4163 HFrEF patients analyzed, 684 (16.4%) were administered ivabradine during their index admission. After matching, there were 617 patients in either group. The results indicated that ivabradine use was not significantly associated with the risk of the primary composite outcome (hazard ratio: 1.10; 95% confidence interval: 0.94-1.29). Similarly, the risk of secondary outcomes and adverse renal events did not significantly differ between the ivabradine and non-ivabradine cohorts (all p > .05). CONCLUSION: For hospitalized acute decompensated heart failure patients who are intolerant to ß-blockers or cannot further titrate them, ivabradine offers a consistent therapeutic effect. No significant disparities were noted between the ivabradine and non-ivabradine groups in heart failure hospitalization and cardiovascular death.

Cardiovascular and renal outcomes in patients with atrial fibrillation and stage 4-5 chronic kidney disease receiving direct oral anticoagulants: a multicenter retrospective cohort study.

The role of direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) and stage 4-5 chronic kidney disease (CKD) is controversial. Electronic medical records from 2012 to 2021 were retrieved for patients with AF and stage 4-5 CKD receiving oral anticoagulants. Patients were separated into those receiving DOACs (dabigatran, rivaroxaban, apixaban, or edoxaban) or vitamin K antagonists (VKA). Primary outcomes included ischemic stroke (IS), systemic thrombosis (SE), major bleeding, gastrointestinal bleeding, hemorrhagic stroke, acute myocardial infarction, cardiovascular death, and all-cause death. Renal outcomes included eGFR declines, creatinine doubling, progression to dialysis, and major adverse kidney events (MAKE). The primary analysis was until the end of follow up and the results at 1-year and 2-year of follow ups were also assessed. 2,382 patients (DOAC = 1,047, VKA = 1,335) between 2012 and 2021 with AF and stage 4-5 CKD were identified. The mean follow-up period was 2.3 ± 2.1 years in DOCAs and 2.6 ± 2.3 years in VKA respectively. At the end of follow up, the DOAC patients had significantly decreased SE (subdistribution hazard ratio [SHR] = 0.50, 95% confidence interval [CI] = 0.34-0.73), composite of IS/SE (SHR = 0.78, 95% CI = 0.62-0.98), major bleeding (HR = 0.77, 95% CI = 0.66-0.90), hemorrhagic stroke (HR = 0.52, 95% CI = 0.36-0.76), and composite of bleeding events (SHR = 0.80, 95% CI = 0.69-0.92) compared with VKA patients. The IS efficacy outcome revealed neutral between DOAC and VKA patients (HR = 1.05, 95% CI = 0.79-1.39). In addition, DOAC patients had significantly decreased rates of eGFR decline > 50% (SHR = 0.75, 95% CI = 0.64-0.87), creatinine doubling (SHR = 0.80, 95% CI = 0.67-0.95), and MAKE (SHR = 0.81, 95% CI = 0.71-0.93). In patients with AF and stage 4-5 CKD, use of DOAC was associated with decreased rates of a composite of ischemic stroke/systemic embolism, a composite of bleeding events, and renal events compared to VKA. Efficacy and safety benefits associated with apixaban at standard doses were consistent throughout follow-up.

Development and Validation of a Novel Risk Score for All-Cause Mortality Risk Stratification Prior to Permanent Pacemaker Implantation in Octogenarians or Older.

Background and Objectives: The demand for permanent pacemaker (PPM) implantation for extremely old patients is increasing. Prior to implanting PPMs, life expectancy evaluation is essential but difficult. We aimed to develop and validate a scoring system for all-cause mortality risk stratification prior to PPM implantation in patients aged ≥80. Materials and Methods: A total of 210 patients aged ≥80 who received PPM implantation were included. Multivariable analysis was performed to assess the effects of different variables on all-cause mortality in a derivation cohort (n = 100). We developed the MELODY score for stratifying all-cause mortality prior to PPM implantation and tested the scoring system in a validation cohort (n = 102). Results: After 4.0 ± 2.7 years of follow-up, 54 patients (54%) had died. The 0.5-, 1- and 2-year all-cause mortality rates were 7%, 10% and 24%, respectively. The MELODY score based on body mass index <21 kg/m2 (HR: 2.21, 95% CI: 1.06-4.61), estimated glomerular filtration rate <30 mL/min/1.73 m2 (3.35, 1.77-6.35), length of hospitalization before PPM implantation >7 days (1.87, 1.02-3.43) and dyspnea as the major presenting symptom (1.90, 1.03-3.50) successfully distinguished patients at high risk of mortality. Patients with MELODY scores ≥3 had a higher risk of mortality compared to those with MELODY scores <3 (8.49, 4.24-17.00). The areas under the receiver operating characteristic curves in predicting 0.5, 1 and 2 years mortality rates were 0.86, 0.81 and 0.74, respectively. The predictive value of the model was confirmed in a validation cohort. Conclusions: The novel scoring system is a simple and effective tool for all-cause mortality risk stratification prior to PPM implantation in patients aged ≥80.

Comparing angiotensin receptor-neprilysin inhibitors with sodium-glucose cotransporter 2 inhibitors for heart failure with diabetes mellitus.

BACKGROUND AND AIMS: Clinical comparisons of angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) treatment in patients with HFrEF and T2DM are limited. This study evaluated the clinical outcomes and treatment benefits of SGLT2i versus ARNI treatment in patients with HFrEF and T2DM in a large real-world data set. METHODS: We identified 1487 patients with HFrEF and T2DM who were undergoing ARNI or SGLT2i treatment for the first time (n = 647 and 840, respectively) between January 1, 2016, and December 31, 2021, and with clinical outcomes of CV death, hospitalization for heart failure (HHF), composite CV outcomes, or renal outcomes. RESULTS: The HHF risk reduction conferred by SGLT2i treatment was more significant than that conferred by ARNI treatment (37.7% vs. 30.4%; 95% confidence interval [CI] 1.06-1.41). SGLT2i use conferred significantly greater renal protection against the doubling of serum creatinine (13.1% vs. 9.3%; 95% CI 1.05-1.75), an estimated glomerular filtration rate decline of > 50% (24.9% vs. 20.0%; 95% CI 1.02-1.45), and progression to end-stage renal disease (3.1% vs. 1.5%; 95% CI 1.62-5.23). The improvements in echocardiographic parameters were comparable between the groups. CONCLUSIONS: Compared with ARNI treatment, SGLT2i treatment was associated with a more significant HHF risk reduction and greater preservation of renal function in patients with HFrEF and T2DM. This study also supports the prioritization of SGLT2i use in these patients when patients' conditions or economic resources need to be considered.

Coronary Artery Spasm-Related Heart Failure Syndrome: Literature Review.

Although heart failure (HF) is a clinical syndrome that becomes worse over time, certain cases can be reversed with appropriate treatments. While coronary artery spasm (CAS) is still underappreciated and may be misdiagnosed, ischemia due to coronary artery disease and CAS is becoming the single most frequent cause of HF worldwide. CAS could lead to syncope, HF, arrhythmias, and myocardial ischemic syndromes such as asymptomatic ischemia, rest and/or effort angina, myocardial infarction, and sudden death. Albeit the clinical significance of asymptomatic CAS has been undervalued, affected individuals compared with those with classic Heberden's angina pectoris are at higher risk of syncope, life-threatening arrhythmias, and sudden death. As a result, a prompt diagnosis implements appropriate treatment strategies, which have significant life-changing consequences to prevent CAS-related complications, such as HF. Although an accurate diagnosis depends mainly on coronary angiography and provocative testing, clinical characteristics may help decision-making. Because the majority of CAS-related HF (CASHF) patients present with less severe phenotypes than overt HF, it underscores the importance of understanding risk factors correlated with CAS to prevent the future burden of HF. This narrative literature review summarises and discusses separately the epidemiology, clinical features, pathophysiology, and management of patients with CASHF.

The cardiovascular and renal effects of glucagon-like peptide 1 receptor agonists in patients with advanced diabetic kidney disease.

BACKGROUND: To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular and renal protective effects in patients with advanced diabetic kidney disease (DKD) with an estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m2. METHODS: In this cohort study, patients with type 2 diabetes mellitus and eGFR < 30 mL/min per 1.73 m2 with a first prescription for GLP-1RAs or dipeptidyl peptidase 4 inhibitors (DPP-4is) from 2012 to 2021 (n = 125,392) were enrolled. A Cox proportional hazard model was used to assess the cardiorenal protective effects between the GLP-1RA and DDP-4i groups. RESULTS: A total of 8922 participants [mean (SD) age 68.4 (11.5) years; 4516 (50.6%) males; GLP-1RAs, n = 759; DPP-4is, n = 8163] were eligible for this study. During a mean follow-up of 2.1 years, 78 (13%) and 204 (13.8%) patients developed composite cardiovascular events in the GLP-1RA and DPP-4i groups, respectively [hazard ratio (HR) 0.88, 95% confidence interval CI 0.68-1.13]. Composite kidney events were reported in 134 (38.2%) and 393 (44.2%) patients in the GLP-1RA and DPP-4i groups, respectively (subdistribution HR 0.72, 95% CI 0.56-0.93). CONCLUSIONS: GLP-1RAs had a neutral effect on the composite cardiovascular outcomes but reduced composite kidney events in the patients with advanced DKD compared with DPP-4is.

Relationship between Inflammation and Vasospastic Angina.

Coronary artery spasm (CAS) is a dynamic coronary stenosis causing vasospastic angina (VSA). However, VSA is a potentially lethal medical condition with multiple presentations, including sudden cardiac death. Despite investigations to explore its pathogenesis, no single mechanism has been found to explain the entire process of VSA occurrence. The roles of elevated local and systemic inflammation have been increasingly recognized in VSA. Treatment strategies to decrease local and systemic inflammation deserve further investigation.

Optimal Heart Rate Control Improves Long-Term Prognosis of Decompensated Heart Failure with Reduced Ejection Fraction.

Background and Objectives: An elevated heart rate is an independent risk factor for cardiovascular disease; however, the relationship between heart rate control and the long-term outcomes of patients with heart failure with reduced ejection fraction (HFrEF) remains unclear. This study explored the long-term prognostic importance of heart rate control in patients hospitalized with HFrEF. Materials and Methods: We retrieved the records of patients admitted for decompensated heart failure with a left ventricular ejection fraction (LVEF) of ≤40%, from 1 January 2005 to 31 December 2019. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure (HHF) during follow-up. We analyzed the outcomes using Cox proportional hazard ratios calculated using the patients' heart rates, as measured at baseline and approximately 3 months later. The mean follow-up duration was 49.0 ± 38.1 months. Results: We identified 5236 eligible patients, and divided them into five groups on the basis of changes in their heart rates. The mean LVEFs of the groups ranged from 29.1% to 30.6%. After adjustment for all covariates, the results demonstrated that lesser heart rate reductions at the 3-month screening period were associated with long-term cardiovascular death, HHF, and all-cause mortality (p for linear trend = 0.033, 0.042, and 0.003, respectively). The restricted cubic spline model revealed a linear relationship between reduction in heart rate and risk of outcomes (p for nonlinearity > 0.2). Conclusions: Greater reductions in heart rate were associated with a lower risk of long-term cardiovascular death, HHF, and all-cause mortality among patients discharged after hospitalization for decompensated HFrEF.

Urinary microRNA in Diabetic Kidney Disease: A Literature Review.

Diabetic kidney disease is the most common primary disease of end-stage kidney disease globally; however, a sensitive and accurate biomarker to predict this disease remains awaited. microRNAs are endogenous single-stranded noncoding RNAs that have intervened in different post-transcriptional regulations of various cellular biological functions. Previous literatures have reported its potential role in the pathophysiology of diabetic kidney disease, including regulation of Transforming Growth Factor-ß1-mediated fibrosis, extracellular matrix and cell adhesion proteins, cellular hypertrophy, growth factor, cytokine production, and redox system activation. Urinary microRNAs have emerged as a novel, non-invasive liquid biopsy for disease diagnosis. In this review, we describe the available experimental and clinical evidence of urinary microRNA in the context of diabetic kidney disease and discuss the future application of microRNA in routine practice.

The Efficacy and Safety of Short-Term Tolvaptan Usage in Patients with Acute Decompensated Heart Failure.

Background: Patients admitted with acute decompensated heart failure (ADHF) have a poor prognosis and poor quality of life due to dyspnea and edema. Tolvaptan, a vasopressin V2 receptor antagonist, is an effective water diuretic. This study aimed to evaluate the efficacy and safety of a short course of tolvaptan to treat volume overload in patients with ADHF. Methods: We conducted a phase III, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a short course of tolvaptan (15 mg/day for 4 days) in hospitalized ADHF patients with volume overload despite the use of conventional diuretics. The primary end-point was the change in body weight after 4 days of treatment. The secondary end-points were the change in intake/output balance, change in serum sodium/potassium concentrations, physician/patient assessed signs and symptoms of heart failure after 4 days of treatment, and all-cause mortality in 1 month. Results: A total of 110 patients were screened, and 91 were randomized to receive 15 mg/day of tolvaptan for 4 days (n = 46) or matching placebo (n = 45). Compared to the placebo-treated patients, tolvaptan significantly reduced body weight (-1.36 ± 2.13 kg in the tolvaptan group vs. -0.59 ± 1.27 kg in the placebo group, p = 0.0394). The tolvaptan group also had a negative intake/urine volume balance compared to the placebo group (-509.3 ± 2788.2 ml vs. 975.5 ± 1903.1 ml, p = 0.0059). The safety profile of tolvaptan was acceptable. Conclusions: Tolvaptan significantly reduced volume overload in hospitalized ADHF patients with volume overload despite the use of conventional diuretics.

Comparison of Sodium-Glucose Cotransporter 2 Inhibitors vs Glucagonlike Peptide-1 Receptor Agonists and Incidence of Dry Eye Disease in Patients With Type 2 Diabetes in Taiwan.

Importance: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been found to improve low-grade systemic and tissue inflammation; however, the association between SGLT2 inhibitor use and the incidence of dry eye disease (DED) has not been explored. Objective: To investigate the association between SGLT2 inhibitor use and dry eye disease in patients with type 2 diabetes (T2D). Design, Setting, and Participants: A retrospective cohort analysis of the largest multi-institutional electronic medical records database in Taiwan was conducted to identify patients with T2D newly receiving SGLT2 inhibitors or glucagonlike peptide-1 receptor agonists (GLP-1 RAs) from 2016 to 2018. Data analysis was performed from March 1 to May 31, 2022. Propensity scores with inverse probability of treatment weighting were generated to enable homogeneous comparisons between the 2 groups. Exposures: Treatment with SGLT2 inhibitors or GLP-1 RAs. Main Outcomes and Measures: Incident dry eye disease, which was defined by clinical diagnoses, plus the related drug prescription. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for the risk of DED. Results: A total of 10 038 and 1077 T2D patients newly receiving SGLT2 inhibitors (mean [SD] age, 59.5 [12.1] years; 5689 [56.7%] men) or GLP-1 RAs (mean [SD] age, 58.5 [41.2] years; 587 [54.5%] men), respectively, were included in the analysis. The incidence of DED was lower in patients newly receiving SGLT2 inhibitors (9.0 events per 1000 person-years) compared with those receiving GLP-1 RAs (11.5 events per 1000 person-years), yielding a hazard ratio of 0.78 (95% CI, 0.68-0.89). Subgroup analyses indicated that the lowered DED risks associated with SGLT2 inhibitors in patients with T2D were similar across different age, sex, blood glucose level, and kidney function groups. Results from the sensitivity analyses (including the propensity score-matching approach, on-treatment analyses, and different follow-up periods of 1, 2, and 3 years) were similar to the main analyses. Conclusions and Relevance: The findings of this study suggest that patients with T2D newly receiving SGLT2 inhibitors may have a lower risk for DED compared with those receiving GLP-1 RAs. Prospective studies are needed to analyze these results.

Associations of thiazide use with skin cancers: a systematic review and meta-analysis.

BACKGROUND: Previous findings on the associations of thiazide use with skin cancers were conflicting. This study aimed to examine the associations of individual thiazide use with skin cancer risk, differentiated by subtypes of skin cancers, geographic regions, and cumulative doses of individual thiazides. METHODS: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for relevant studies on January 5, 2022, scanned the references of included studies, and consulted experts. We included case-control and cohort studies or randomized trials reporting the associations of individual thiazide or thiazide-like diuretics use with skin cancers. Non-melanoma skin cancer (NMSC) and melanoma were analysed separately. A random-effects model meta-analysis was conducted for pooled odds ratio (OR) and hazard ratio (HR) for skin cancers related to individual thiazide use. RESULTS: We included 15, 5, and 5 case-control or cohort studies reporting the risk for skin cancers associated with hydrochlorothiazide, bendroflumethiazide, and indapamide use, respectively, with 17,848,313 participants. The meta-analysis showed associations of hydrochlorothiazide use with increased risk of NMSC (OR 1.16, 95% CI 1.08-1.24; HR 1.26, 95% CI 1.04-1.54), squamous cell carcinoma (SCC) (OR 1.32, 95% CI 1.06-1.65; HR 1.61, 95% CI 0.97-2.67), and melanoma (OR 1.11, 95% CI 1.02-1.20; HR 1.03, 95% CI 0.93-1.14). The increased risks for SCC were associated with high cumulative doses of hydrochlorothiazide (OR 2.56, 95% CI 1.43-4.57; HR 1.20, 95% CI 1.00-1.45). Hydrochlorothiazide use was associated with different subtypes of melanoma including superficial spreading (OR 1.18, 95% CI 1.05-1.33), nodular (OR 1.23, 95% CI 1.08-1.39), and lentigo maligna melanoma (OR 1.33, 95% CI 1.08-1.65). Various cumulative doses of hydrochlorothiazide were associated with increased odds for melanoma. However, the associations of hydrochlorothiazide use with increased risk of NMSC and melanoma only appeared in non-Asian countries. No meaningful increase in the risk for skin cancers was associated with bendroflumethiazide and indapamide. CONCLUSIONS: Hydrochlorothiazide is associated with an increased risk for NMSC (especially SCC) and melanoma in non-Asian countries, whereas bendroflumethiazide and indapamide are not associated with a meaningful risk for skin cancers. Healthcare professionals and patients should be informed of the different risk profiles of skin cancers associated with different thiazides, cumulative doses, and regions. TRIAL REGISTRATION: PROSPERO CRD42021234317 .

Association between sodium glucose co-transporter 2 inhibitors and incident glaucoma in patients with type 2 diabetes: A multi-institutional cohort study in Taiwan.

PURPOSE: Type 2 diabetes (T2D) is an important risk factor for glaucoma, and sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to protect the optic nerves. We therefore aimed to evaluate the association between SGLT2 inhibitors and incident glaucoma. METHODS: This retrospective cohort study analyzed the largest multi-institutional electronic medical records database in Taiwan, containing data of over a million individuals. We included T2D patients newly prescribed SGLT2 inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) from 2016 to 2018. Our primary outcome was incident glaucoma diagnosis between initiation of SGLT2 inhibitors or GLP-1 RAs, and 31st March 2021. After applying inverse probability of treatment weighting (IPTW) to increase homogeneity between the two treatment groups, we estimated hazard ratios (HR) with 95% confidence intervals (CI) for the risk of glaucoma, based on Cox proportional hazards regression models. RESULTS: We included 9,927 and 1,065 T2D patients who had been newly prescribed SGLT2 inhibitors or GLP-1 RAs, respectively. Lower risk of incident glaucoma was observed in patients receiving SGLT2 inhibitors (7.9 events per 1,000 person-years), compared to those receiving GLP-1 RAs (10.0 events per 1,000 person-years), with an HR of 0.81 (95% CI: 0.69-0.95). Multiple sensitivity analyses and a negative control outcome analysis confirmed the robustness of our main findings. CONCLUSION: This study suggests that T2D patients newly prescribed SGLT2 inhibitors have a reduced risk of incident glaucoma, compared to those prescribed GLP-1 RAs, in clinical practice. Future prospective studies are suggested to confirm this association.

Dynamic Echocardiographic Assessments Reveal Septal E/e' Ratio as Independent Predictor of Intradialytic Hypotension in Maintenance for Hemodialysis Patients with Preserved Ejection Fraction.

BACKGROUND: Intradialytic hypotension (IDH) is a frequent and grave complication of hemodialysis (HD). However, the dynamic hemodynamic changes and cardiac performances during each dialytic session have been rarely explored in patients having IDH. METHODS: Seventy-six HD patients (IDH = 40, controls = 36) were enrolled. Echocardiography examinations were performed in all patients at the pre-HD, during-HD and post-HD phases of a single HD session. A two-way analysis of variance was applied to compare differences of echocardiographic parameters between IDH and controls over time. The risk association was estimated by using a logistic regression analysis. RESULTS: The IDH patients had a higher ejection fraction during HD followed by a greater reduction at the post-HD phase than the controls. Significant decreases in septal ratios of transmitral flow velocity to annular velocity (E/e') over times were detected between IDH patients and controls after adjusting for gender, age and ultrafiltration (p = 0.016). A lower septal E/e' ratio was independently associated with IDH (OR = 0.040; 95% CI = 0.003-0.606; p = 0.02). In contrast, significant systolic and diastolic dysfunctions over time were found in diabetic IDH compared to non-diabetic counterparts. CONCLUSION: The septal E/e' ratio was a significant predictor for IDH.

Academic outcome and moderator of flipped classroom learning program "Teaching on the Run".

BACKGROUND: Flipped classroom (FC) style Australian faculty development program Teaching on the Run (TOTR) was introduced into Chang Gung Memorial Hospital since 2014. However, its effectiveness in Taiwan has not been formally assessed. This work intended to examine the learning gain of TOTR and identify the moderators of FC outcome by using TOTR as a representative model of FC. METHODS: A non-controlled before-after study was undertaken by retrospective analysis of learning data collected during TOTR workshop. Multiple choice questions were tested at baseline (pre-test), after pre-class learning (mid-test) and after classroom activity (post-test) to assess the learning gain. All available demographic and learning variables were included in the moderator analysis. RESULTS: Stepwise and significant improvement in exam scores was noted from pre-test to mid-test and post-test (p < 0.001 for both). Univariate analysis showed pre-test scores, mid-test scores, class participation and session of TOTR were significantly associated with post-test scores. However, multivariate analysis by general linear model showed only mid-test scores and session of TOTR were significant predictor of post-test score. Generalized estimating equations analysis showed that class participation is a significant moderator that influence the scores change from mid-test to post-test. CONCLUSION: TOTR is effective in improving knowledge of teaching skills for clinical teachers in Taiwan. Achievement in pre-class learning, class participation and learner factor are potential moderators of the FC outcome. Thus, facilitators should try their best to promote a good achievement in pre-class learning and engagement in classroom activity in FC style learning.

Quantifying the Effects of Climate Factors on Carbon Monoxide Poisoning: A Retrospective Study in Taiwan.

Background: Carbon monoxide (CO) poisoning is the leading cause of poisoning death worldwide, but associations between CO poisoning and weather remain unclear. Objective: To quantify the influence of climate parameters (e.g., temperature, relative humidity, and wind speed) on the incidence risk of acute CO poisoning in Taiwan. Methods: We used negative binomial mixed models (NBMMs) to evaluate the influence of weather parameters on the incidence risk of acute CO poisoning. Subgroup analyses were conducted, based on the seasonality and the intentionality of acute CO poisoning cases. Results: We identified a total of 622 patients (mean age: 32.9 years old; female: 51%) with acute CO poisoning in the study hospital. Carbon monoxide poisoning was associated with temperature (beta: -0.0973, rate ratio (RR): 0.9073, p < 0.0001) but not with relative humidity (beta: 0.1290, RR: 1.1377, p = 0.0513) or wind speed (beta: -0.4195, RR: 0.6574, p = 0.0806). In the subgroup analyses, temperature was associated with the incidence of intentional CO poisoning (beta: 0.1076, RR: 1.1136, p = 0.0333) in spring and unintentional CO poisoning (beta: -0.1865, RR: 0.8299, p = 0.0184) in winter. Conclusion: Changes in temperature affect the incidence risk for acute CO poisoning, but the impact varies with different seasons and intentionality in Taiwan. Our findings quantify the effects of climate factors and provide fundamental evidence for healthcare providers to develop preventative strategies to reduce acute CO poisoning events.

Differences in outcomes of hospitalizations for heart failure after SGLT2 inhibitor treatment: effect modification by atherosclerotic cardiovascular disease.

BACKGROUND: The treatment effects on hospitalization for heart failure (hHF) from sodium-glucose cotransporter 2 (SGLT2) inhibitors may vary among type 2 diabetes (T2D) patients depending on whether or not they have established atherosclerotic cardiovascular diseases (ASCVD). We aimed to examine differences in hHF outcomes after dapagliflozin or empagliflozin use between T2D patients with and without a history of established ASCVD. METHODS: We conducted a retrospective multi-institutional cohort study in Taiwan. We included T2D patients newly receiving dapagliflozin or empagliflozin during 2016-2019, and followed them up until December 31, 2020. We implemented 1:1 propensity score matching to create homogenous groups for comparisons. We generated Cox proportional hazard models to compare the risk of hHF between dapagliflozin and empagliflozin (reference group). We included interaction terms of SGLT2 inhibitor and ASCVD history in the regression models to examine effect modification by ASCVD. RESULTS: We included a total cohort of 9,586 dapagliflozin new users and 9,586 matched empagliflozin new users. The overall hHF risks were similar for dapagliflozin and empagliflozin (HR: 0.90, 95% CI 0.74-1.09). However, differential hHF risks between dapagliflozin and empagliflozin were observed only in the subgroup without ASCVD (HR: 0.67, 95% CI 0.49-0.90), while not in the subgroup with ASCVD (HR: 1.12, 95% 0.87-1.45), and the p-value for examining interaction was 0.0097. CONCLUSION: In this study, history of established ASCVD was associated with different hHF risks among SGLT2 inhibitors. For T2D patients without ASCVD, dapagliflozin may offer a more favorable hHF reduction effect, compared to empagliflozin, in clinical practice. Future prospective studies should be conducted to validate our findings.

Guillain-​Barré Syndrome Associated with COVID-19 Vaccination.

We conducted a multi-institutional study in Taiwan and a systematic review of the literature for reports of Guillain-​Barré syndrome after coronavirus disease vaccination. This condition, mostly the classic form and the acute inflammatory demyelinating polyneuropathy subtype, has been reported in 39 cases and has occurred within 2 weeks of vaccine administration.