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COVID-19 has not only affected the respiratory but the cardiovascular system. Taiwan has encountered a less severe COVID-19 pandemic. We reported the current situation in Taiwan. In this study, we retrospectively analyzed the data from our cardio-oncology program since October of 2019 to April of 2020 (the initial months of COVID-19 pandemic). In our cardio-oncology program, newly diagnosed breast cancer patients preparing for epirubicin therapy were included. Echocardiography, 6-min walking distance and major adverse cardiovascular events (MACEs) were recorded. To evaluate whether the social atmosphere affects cardio-oncology care, we analyzed the objective (physical) and subjective (emotional) parameters before and after January 21, 2020, when the first case of COVID-19 was confirmed in Taiwan. There was no significant decrease in patients’ return ratio and LVEFs. However, there was a trend of subjective shortness of breath reported by the patients but no decline in 6 MWT. Notably, none of the enrolled patients reported MACEs during the COVID pandemic. We observed an impact of anxiety on patients receiving epirubicin but it did not influence their return ratio.

Androgen deprivation therapy (ADT) includes bilateral orchiectomy or long-acting gonadotropin-releasing hormone (GnRH) agonists/antagonists. It remains controversial with respect to ADT associated cardiovascular outcomes. Hereby, we compared the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with prostate cancer receiving either surgical castration or GnRH therapies.Using the Taiwan Cancer Registry and Taiwan's National Health Insurance Research Database, we identified 8,413 patients receiving GnRH therapies compared with 694 receiving surgical castration from 2008 to 2017. The median followup duration was 3 years.The crude incidences of 3-year mortality and MACCEs were 19.90% vs 26.51% and 8.23% vs 8.65% in patients receiving GnRH therapies or surgical castration, respectively. After adjusting for age, cancer stage and comorbidities, despite no significant differences in MACCEs between groups there was a slight increase in the incidence of acute myocardial infarction (AMI) in patients receiving surgical castration compared with those receiving GnRH therapies. The mortality adjusted hazard ratios of MACCEs and AMI among patients receiving surgical castration were 1.11- and 1.8-fold higher than those receiving GnRH therapies. Notably, in subgroup analysis regarding cancer stage, patients with cancer stage IV showed the most significantly increasing risk of AMI in those receiving surgical castration compared with GnRH therapies.Collectively, we indicated an increased risk of AMI in patients with prostate cancer, especially in patients receiving surgical castration rather than those receiving GnRH therapies. Our findings highlight concerns regarding the cardiac safety of surgical castration compared with GnRH therapies.

In this paper, we study the problem of federated learning over a wireless channel with user sampling, modeled by a fading multiple access channel, subject to central and local differential privacy (DP/LDP) constraints. It has been shown that the superposition nature of the wireless channel provides a dual benefit of bandwidth efficient gradient aggregation, in conjunction with strong DP guarantees for the users. Specifically, the central DP privacy leakage has been shown to scale as $\mathcal {O}(1/K^{1/2})$ , where $K$ is the number of users. It has also been shown that user sampling coupled with orthogonal transmission can enhance the central DP privacy leakage with the same scaling behavior. In this work, we show that, by jointly incorporating both wireless aggregation and user sampling, one can obtain even stronger privacy guarantees. We propose a private wireless gradient aggregation scheme, which relies on independently randomized participation decisions by each user. The central DP leakage of our proposed scheme scales as $\mathcal {O}(1/K^{3/4})$ . In addition, we show that LDP is also boosted by user sampling. We also present analysis for the convergence rate of the proposed scheme and study the tradeoffs between wireless resources, convergence, and privacy theoretically and empirically for two scenarios when the number of sampled participants are $(a)$ known, or $(b)$ unknown at the parameter server.

Background With emerging evidence on the efficacy of adding dapagliflozin to standard care for patients with heart failure with reduced ejection fraction (HFrEF), this study assessed the cost-effectiveness of add-on dapagliflozin to standard care versus standard care alone for HFrEF from the perspective of healthcare systems in the Asia–Pacific region. Methods A Markov model was applied to project the outcomes of treatment in terms of lifetime medical cost and quality-adjusted life-years. The transition probabilities between health states in the model were obtained from the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction trial. Country-specific costs and utilities were extracted for modeling. The incremental cost-effectiveness ratio against a country-specific willingness-to-pay threshold was applied to determine the cost-effectiveness of treatment. A series of sensitivity analyses were performed to ensure the robustness of the study results. Costs are presented in 2020 United States dollars. Results The incremental cost-effectiveness ratios for add-on dapagliflozin versus standard care alone were $5277, $9980, $12,305, $16,705, and $23,227 per quality-adjusted life-year gained in Korea, Australia, Taiwan, Japan, and Singapore, respectively. When using add-on dapagliflozin to standard care versus standard care alone, ~ 100% of simulations were cost-effective at a willingness-to-pay threshold of one gross domestic product per capita of the given Asia–Pacific country; however, the probability of being cost-effective for using add-on dapagliflozin decreased when the time horizon for simulation was restricted to 18 months and when the cardiovascular mortality for the two treatments (43.8% and 33.0%, respectively) was assumed to be the same. The cost-effectiveness results were most sensitive to cardiovascular mortality of treatment. Conclusions Adding dapagliflozin to standard care is cost-effective for HFrEF in healthcare systems in the Asia–Pacific region, which supports the rational use of dapagliflozin for HFrEF in this region.

Aims The Registry to Evaluate Early and Long‐Term PAH Disease Management (REVEAL) risk scores differentiate survivals in patients with pulmonary arterial hypertension (PAH). However, measurements of N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) in the peripheral blood may not adequately reflect early‐stage decompensated heart failure (HF). Given that right heart catheterization (RHC) can facilitate measurements of intracardiac NT‐proBNP, in this study our aim was to evaluate the predictive role of right ventricular (RV) NT‐proBNP measurements in patients with PAH. Methods and results We prospectively collected intracardiac blood samples for NT‐proBNP measurements from patients diagnosed with World Health Organization Group I PAH during RHC. Clinical information including the aetiology of PAH (idiopathic, connective tissue disease, or congenital heart disease) and REVEAL scores were recorded. The primary endpoint was hospitalization for decompensated HF; median duration of follow‐up was 28 months. Among the 62 patients evaluated, 12 reached the designated endpoint. REVEAL risk scores were higher among patients hospitalized for HF. We detected no significant differences in plasma NT‐proBNP levels in peripheral circulation, in the right atrium, or in pulmonary arterial blood; however, significantly higher levels of NT‐proBNP were detected in the RV in patients diagnosed with PAH. RV NT‐proBNP was a sensitive predictor (cut‐off value 1500 pg/mL) of subsequent hospitalization for HF. Our findings indicate that RV NT‐proBNP levels add predictive value to REVEAL scores with respect to future hospitalization due to HF. Conclusions Right ventricular NT‐proBNP levels combined with REVEAL 2.0 could predict the development of subsequent HF in patients with PAH and may be a potential biomarker.

Right ventricular (RV) function is a critical determinant of survival in patients with pulmonary arterial hypertension (PAH). While miR-21 is known to associate with vascular remodeling in small animal models of PAH, its role in RV remodeling in large animal models has not been characterized. Herein, we investigated the role of miR-21 in RV dysfunction using a sheep model of PAH secondary to pulmonary arterial constriction (PAC). RV structural and functional remodeling were examined using ultrasound imaging. Our results showed that post PAC, RV strain significantly decreased at the basal region compared with t the control. Moreover, such dysfunction was accompanied by increases in miR-21 levels. To determine the role of miR-21 in RV remodeling secondary to PAC, we investigated the molecular alteration secondary to phenylephrine induced hypertrophy and miR21 overexpression in vitro using neonatal rat ventricular myocytes (NRVMs). We found that overexpression of miR-21 in the setting of hypertrophic stimulation augmented only the expression of proteins critical for mitosis but not cytokinesis. Strikingly, this molecular alteration was associated with an eccentric cellular hypertrophic phenotype similar to what we observed in vivo PAC animal model in sheep. Importantly, this hypertrophic change was diminished upon suppressing miR-21 in NRVMs. Collectively, our in vitro and in vivo data demonstrate that miR-21 is a critical contributor in the development of RV dysfunction and could represent a novel therapeutic target for PAH associated RV dysfunction.

Coronary flow velocity (CFV) is reduced in pathologic cardiac hypertrophy. This functional reduction is linked to adverse cardiac remodeling, hypertension and fibrosis, and angiotensin II (AngII) is a key molecular player. Angiotensin receptor blockers (ARBs) are known to attenuate adverse cardiac remodeling and fibrosis following increased afterload, while the mechanism by which these drugs offer clinical benefits and regulate hemodynamics remains unknown. To establish a direct connection between coronary flow changes and angiotensin-induced hypertension, we used a Doppler echocardiographic method in two distinct disease models. First, we performed serial echocardiography to visualize coronary flow and assess heart function in patients newly diagnosed with hypertension and currently on ARBs or calcium channel blockers (CCBs). CFV improved significantly in the hypertensive patients after 12 weeks of ARB treatment but not in those treated with CCBs. Second, using murine models of pressure overload, including Ang II infusion and aortic banding, we mimicked the clinical conditions of Ang II- and mechanical stress-induced hypertension, respectively. Both Ang II infusion and aortic banding increased the end-systolic pressure-volume relationship and cardiac fibrosis, but interestingly, only Ang II infusion resulted in a significant reduction in CFV and corresponding activation of pressure-sensitive proteins, including connective tissue growth factor, hypoxia-inducible factor 1α and signal transducer and activator of transcription 3. These data support the existence of a molecular and functional link between AngII-induced hemodynamic remodeling and alterations in coronary vasculature, which, in part, can explain the clinical benefit of ARB treatment in hypertensive patients.

How renal function influences post-acute myocardial infarction (AMI) cardiac remodeling and outcomes remains unclear. This study evaluated the impact of levels of renal impairment on drug therapy, echocardiographic parameters, and outcomes in patients with AMI undergoing percutaneous coronary intervention (PCI). A total of 611 patients diagnosed with AMI underwent successful PCI, and two echocardiographic examinations were performed within 1 year after AMI. Patients were categorized according to Group 1: severely impaired estimated glomerular filtration rate (eGFR)

Cancer patients with diabetes have an increasing risk of Dox-induced cardiotoxicity. Despite previous studies reporting benefits of dapagliflozin on the cardiovascular system, it remains unknown whether dapagliflozin has a cardioprotective effect in cancer patients with diabetes. We aimed to investigate the potential of dapagliflozin for preventing doxorubicin (Dox)-induced cardiotoxicity. Using Taiwan National Health Insurance Database, the incidence of heart failure of cancer patients with or without diabetes was investigated. Streptozotocin (STZ)-induced diabetic rats were pretreated with oral dapagliflozin for 6 weeks followed by Dox for 4 weeks via intraperitoneal injection. Sequential echocardiography was applied to assess cardiac function. For in vitro analysis, cardiomyocytes cultured in high glucose were treated with dapagliflozin at 10 μM and subsequently exposed to Dox at 1 μM. Apoptosis and endoplasmic reticulum (ER) stress-related protein expression were measured. Among the studied patients, those with diabetes had a higher risk of major adverse cardiovascular events including the development of heart failure. In diabetic rats, dapagliflozin reduced cardiac fibrosis and significantly improved cardiac function. Dapagliflozin effectively inhibited Dox-induced apoptosis and reactive oxygen species in cardiomyocytes under high glucose. Mechanistically, we showed that dapagliflozin decreased the cardiac expression of Bax and cleaved caspase 3 but increased Bcl-2. Dapagliflozin also significantly reduced ER stress-associated proteins including GRP78, PERK, eIF-2α, ATF-4, and CHOP. Our study revealed for the first time that dapagliflozin mitigated Dox-induced cardiomyocyte apoptosis in diabetes. These results indicate that dapagliflozin could be useful for preventing cardiotoxicity in diabetic cancer patients receiving Dox treatment.

Dapagliflozin (DAPA), a sodium–glucose cotransporter 2 inhibitor, is approved for treatments of patients with diabetes. The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial disclosed DAPA’s benefits in symptomatic heart failure, but the underlying mechanism remains largely unknown. In this longitudinal and prospective study, we investigated changes of left ventricular functions including speckle tracking in patients with diabetes who were free from symptomatic heart failure post–DAPA treatment. Using a rat model with streptozotocin-induced diabetes, we measured the effects of DAPA on myocardial function. In patients with diabetes, following 6 months of DAPA treatment, despite no significant changes in left ventricular ejection fraction, the diastolic function and longitudinal strain improved. Likewise, compared with control, the diabetic rat heart developed pronounced fibrosis and a decline in strain and overall hemodynamics, all of which were mitigated by DAPA treatment. In contrast, despite insulin exerting a glucose-lowering effect, it failed to improve myocardial function and fibrosis. In our in vitro study, under high glucose cardiomyocytes showed significant activations of apoptosis, reactive oxygen species, and endoplasmic reticulum (ER) stress–associated proteins, which were attenuated by the coincubation of DAPA. Mechanistically, DAPA suppressed ER stress, reduced myocardial fibrosis, and improved overall function. The results can lead to further improvement in management of left ventricular function in patients with diabetes.

This study aimed to investigate the cost-effectiveness of low-dose rivaroxaban plus aspirin versus aspirin alone for patients with stable cardiovascular diseases in the Taiwan setting. We constructed a Markov model to project the lifetime direct medical costs and quality-adjusted life-years of both therapies. Transitional probabilities were derived from the COMPASS trial, and the costs and utilities were obtained from the Taiwan National Health Insurance Database and published studies. One-way, scenario, subgroup, and probabilistic sensitivity analyses were performed to assess the uncertainty. Incremental cost-effectiveness ratio was presented as the outcome. The threshold of willingness-to-pay was set at US$76,368 (3 times the gross domestic product per capita of Taiwan). All analyses were operated by TreeAge 2019 and Microsoft Excel. The incremental cost-effectiveness ratios of rivaroxaban plus aspirin versus aspirin alone in the patients with stable cardiovascular diseases, coronary artery diseases, and peripheral artery diseases were US$83,459, US$69,852 and −US$13,823 per quality-adjusted life-year gained, respectively. The probabilistic sensitivity analyses showed that the probabilities of cost-effectiveness for the regimen with rivaroxaban among those with cardiovascular diseases and coronary artery diseases were 44.1% and 65.3% at US$76,368. Low-dose rivaroxaban plus aspirin is less likely to be a cost-effective alternative to aspirin in secondary prevention for the patients with stable cardiovascular diseases; however, among these patients, the regimen may have pharmacoeconomic incentives for the group merely having chronic coronary artery diseases from the Taiwan national payer’s perspective. The pharmacoeconomic incentives are influenced by the drug price, event treatment fees, and willingness-to-pay threshold.

Anthracycline anticancer drugs such as epirubicin and doxorubicin may induce myocardial dysfunction, leading to poor prognosis. Early detection of minor left ventricular (LV) myocardial dysfunction is important for the prevention of anthracylcine-induced cardiotoxicity. Using layer-specific speckle tracking echocardiography (STE), we investigated the progressive distribution of myocardial dysfunction in both breast cancer patients and an animal toxicity model.Patients with preserved LV ejection fraction (LVEF) preparing for epirubicin chemotherapy (N = 125) were prospectively enrolled. Layer-specific STE, including LV longitudinal and circumferential strains on subepicardium and subendocardium, were evaluated at baseline and after the first cycle, third cycle and six months of epirubicin therapy. A decline of LVEF above 10% to55% at six months was defined as cardiotoxicity. These same strain measures were obtained in doxorubicin-treated rats and the distribution of myocardial fibrosis evaluated.In patients developing cardiotoxicity, LV longitudinal strain on subendocardium (LVLSendo) was significantly reduced after three cycles of therapy despite no significant changes in conventional LV systolic, diastolic parameters as well as LV circumferential strains at that moment. Compared to conventional echocardiographic parameters, LVLSendo was significantly predictive of cardiotoxicity. Declines in LVLSendo were also observed in doxorubicin-treated rats at an early stage. These reductions also predicted significant fibrosis in the subendocardial layer.LVLSendo is useful for the early detection of minor cardiac dysfunction during chemotherapy, thereby implicating endocardial involvement in the development of cardiotoxicity.

Electrocardiograms (ECGs) provide important information for diagnosing cardiovascular diseases. In clinical practice, the conventional Ag/AgCl electrode is generally used; however, it is not suitable for long-term ECG measurement because of the risk of allergic reactions on the skin and the dying issue of electrolytic gels. In previous studies, several dry electrodes have been proposed to address these issues. However, most dry electrodes, which are the mode of conductive materials, have to contact the skin well and are easily affected by motion artifacts in daily life. In the smart clothes developed in this study, a noncontact electrode was used to assess the biopotential across the clothes to prevent skin irritation and discomfort. Moreover, a three-dimensional parametric model based on anthropometric data was built, and the technique of customized product design was introduced into the smart clothes development process to reduce the influence of motion artifacts. The experimental results show that the proposed smart clothes can maintain a good ECG signal quality stably under motion from different activities.

Background: EMPEROR-Reduced trial provides promising evidence on the efficacy of empagliflozin adding to the standard treatment in patients with heart failure and reduced ejection fraction (HFrEF). This study aimed to investigate the cost-effectiveness of add-on empagliflozin vs. standard therapy alone in HFrEF from the perspective of the Asia-Pacific healthcare systems.Methods: A Markov model was constructed to simulate HFrEF patients and to project the lifetime direct medical costs and quality-adjusted life years (QALY) of both therapies. Transitional probabilities were derived from the EMPEROR-Reduced trial. Country-specific costs and utilities were extracted from published resources. Incremental cost-effectiveness ratio (ICER) against willingness to pay (WTP) threshold was used to examine the cost-effectiveness. A series of sensitivity analyses was performed to ensure the robustness of the results.Results: The ICERs of add-on empagliflozin vs. standard therapy alone in HFrEF were US$20,508, US$24,046, US$8,846, US$53,791, US$21,543, and US$20,982 per QALY gained in Taiwan, Japan, South Korea, Singapore, Thailand, and Australia, respectively. Across these countries, the probabilities of being cost-effective for using add-on empagliflozin under the WTP threshold of 3-times country-specific gross domestic product per capita were 93.7% in Taiwan, 95.6% in Japan, 96.3% in South Korea, 94.2% Singapore, 51.9% in Thailand, and 95.9% in Australia. The probabilities were reduced when shortening the time horizon, assuming the same cardiovascular mortality for both treatments, and setting lower WTP thresholds.Conclusion: Adding empagliflozin to HFrEF treatment is expected to be a cost-effective option among the Asia-Pacific countries. The cost-effectiveness is influenced by the WTP thresholds of different countries.

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Aims Despite being an essential therapy for breast cancer, trastuzumab has potential risks of cardiotoxicity. The incidence of trastuzumab-related major adverse cardiac and cerebrovascular event (MACCE) and its predictors remain unknown in Taiwan. Methods and results Through a three-hospital retrospective cohort study, we analyzed the incidence of MACCE in 386 breast cancer patients exposure to trastuzumab from 2010 to 2018. To further reconfirm our findings, in a nationwide study using the Taiwanese National Health Insurance Research Database and National Cancer Registry, we identified 13502 women diagnosed with breast cancer who received chemotherapy from 2010 to 2015 and found 6751 women who received initial treatment with trastuzumab. After 1:1 propensity score matching with trastuzumab nonusers, the incidence of MACCE was measured with a median follow-up of 36 months. In the hospital-based study, among 386 patients receiving trastuzumab, the 5-year incidences of MACCE and heart failure (HF) were 5.4% and 2.8%, respectively. In the national cohort, the crude incidences of MACCEs and HF were 4.67% and 3.21%, respectively. After adjustment for age and comorbidities, the hazard ratio of MACCE was 1.485 (95% CI 1.246–1.769). Notably, among the endpoints, only the hazard ratio of HF was significantly higher in patients receiving trastuzumab than in nonusers. In the subgroup analysis, except for patients also using taxanes, those receiving trastuzumab had a higher risk of MACCE than nonusers. Conclusions From clinical observations in a nationwide cohort, we found an increased risk of MACCE, especially HF, in patients receiving trastuzumab. Given that its cardiotoxicity is independent of traditional cardiovascular risks, our findings highlight critical concerns regarding the cardiac safety of trastuzumab use. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Chi-Mei Medical Center, National Cheng Kung University Hospital

In this paper, we consider the problem of wireless federated learning, where the users wish to jointly train a machine learning model with the help of a parameter server. During the training, the local gradients from the users are aggregated over a wireless channel. Typically, coefficients of the local gradients are aligned by power control techniques to ensure that the estimated aggregated gradient is an unbiased estimator of the true gradient. However, schemes that align gradients require coordination, can be challenging to implement in practice, and often lead to degraded performance due to heterogeneity of users’ channels. In this paper, we show that alignment of gradients for wireless FL is not always necessary for convergence. Specifically, we consider non-convex loss functions, and derive conditions under which misaligned wireless gradient aggregation still converges to a stationary point. We also present experimental results to show that transmitting at full power can outperform aligned gradient aggregation depending on the heterogeneity of users’ channels.

Purpose Wall shear stress (WSS), a type of friction exerted on the artery wall by flowing blood, is considered a crucial factor in atherosclerotic plaque development. Currently, achieving a reliable WSS mapping of an artery noninvasively by using existing imaging modalities is still challenging. In this study, a WSS mapping based on vector Doppler flow velocity estimation was proposed to measure the dynamic WSS on the human femoral artery. Methods Because ultrafast ultrasound imaging was used here, flow-enhanced imaging was also performed to observe the moving blood flow condition. The performance of WSS mapping was verified using both straight (8 mm in diameter) and stenosis (70% of stenosis) phantoms under a pulsatile flow condition. A human study was conducted from five healthy volunteers. Results Experimental results demonstrated that the WSS estimation was close to the standard value that was obtained from maximum velocity estimation in straight phantom experiments. In a stenosis phantom experiment, a low WSS region was observed at a site downstream of an obstruction, which is a high-risk area for plaque formation. Dynamic WSS mapping was accomplished in measurement in the femoral artery bifurcation. In measurements, the time-averaged WSS of the common femoral artery, superficial femoral artery, and deep femoral artery was 0.52± 0.19, 0.44 ± 0.21, and 0.29 ± 0.16 Pa, respectively, for the anterior wall and 0.29 ± 0.11, 0.54 ± 0.24, and 0.23 ± 0.10 Pa, respectively, for the posterior wall. Conclusions All results indicated that WSS mapping has the potential to be a useful tool for vessel duplex scanning in the future.

Extrinsic compression of the left atrium (LA) due to esophageal achalasia has been considered a rare occurrence. Patients might present with dysphagia, dyspnea, and even hemodynamic compromise simultaneously. Prompt detection with a thorough differential diagnosis is crucial for subsequent management. In this case report, we present a patient with LA compression by esophageal achalasia and performed a literature review to gather information as regards the clinical manifestation, diagnosis, and treatment strategy of this rare disease.A 59-year-old man with intermittent palpitation, heartburn sensation, and difficulty swallowing came to our emergency department due to acute onset of chest compression and breathlessness after a large meal. As per his chest X-ray, dilated mediastinum and small gastric bubble were noted. Electrocardiogram implied left atrial enlargement, and the Holter monitor reported one episode of paroxysmal atrial fibrillation attack during his meal. Transthoracic echocardiogram showed a round-shaped, well-bordered, hyperechogenic, and heterogeneous mass compressing the LA irrespective of the systolic or diastolic phase. A chest contrast-enhanced computed tomography scan was then performed, wherein it showed diffuse esophageal dilatation with a smoothly thickening wall aligned compressing the LA. Meanwhile, the barium swallow esophagogram revealed contrast pooling at the esophagogastric junction with a bird beak shape. Accordingly, extrinsic compression of LA by esophageal achalasia was diagnosed.Esophageal achalasia compressing LA has been considered rare. Remarkably, given that a patient is presenting with dysphagia and concurrent chest tightness, palpitation, and dyspnea after swallowing food, the clinicians should keep this diagnosis in mind. Careful history review to clarify the causal relationship between the symptoms, specific findings on electrocardiogram and chest X-ray, and utilization of echocardiography and esophagography are beneficial for a prompt and accurate diagnosis.

BackgroundHeart failure (HF) has become a healthcare challenge worldwide. Recently, certain trials on sodium-glucose co-transporter-2 (SGLT2) inhibitor showed benefits for patients with HF. This study aimed to systematically review the literature and investigate the clinical efficacy of SGLT2 inhibitors in cardiovascular events among patients with and without HF. Methods We searched randomized controlled trials (RCTs) in PubMed, Cochrane databases, Embase, and ClinicalTrials.gov registry form inception to October 2020. Dichotomous variables were pooled using a random-effects model and presented with a risk ratio (RR) and 95% confidence interval (CI). Subgroup meta-analyses were carried out by high/low SGLT2/SGLT1 selectivity and individual SGLT2 inhibitor.ResultsA total of 10 RCTs comprised of 52,607 patients were eligible for the analyses. SGLT2 inhibitors reduced the risk of total cardiovascular death or hospitalization for HF (RR 0.79, [95% CI: 0.74 to 0.84]; p < 0.01, I2 = 31%). Apart from stroke, SGLT2 inhibitors contributed to a risk reduction in major adverse cardiovascular events (MACE, RR 0.93, [95% CI: 0.88 to 0.99]; p = 0.03, I2 = 0), all-cause mortality (RR 0.92, [95% CI: 0.85 to 0.99]; p = 0.03, I2 = 0), cardiovascular death (RR 0.91, [95% CI: 0.83 to 0.99]; p = 0.03, I2 = 0), hospitalization for HF (RR 0.72, [95% CI: 0.66 to 0.79]; p < 0.01, I2 = 0), and myocardial infarction (RR 0.89, [95% CI: 0.80 to 0.99]; p = 0.03, I2 = 0). For HF patients, SGLT2 inhibitors had more clinical benefits in terms of all-cause mortality and cardiovascular death, while advantages were observed in MACE and myocardial infarction for non-HF patients. Furthermore, SGLT2 inhibitors with low SGLT2/SGLT1 selectivity have better efficacy for hospitalization of HF, compared with high-selectivity inhibitors (RR 0.51 [95% CI: 0.35-0.75] versus 0.73 [95% CI: 0.66-0.81] for HF patients). ConclusionsSGLT2 inhibitors significantly mitigate hospitalization for HF. Between HF and non-HF populations, this regimen reduce mortality for HF patients and improve MACE and myocardial infarction for non-HF patients. The SGLT2 inhibitor, mixed with the effect of SGLT1 inhibitors, may lead to a lower risk of hospitalization for HF.

Peritoneal dialysis (PD) is an important treatment method for patients with end stage renal disease. Since its introduction in 1975, clinical studies have shown that PD can improve patient survival, retain residual renal function, and lower the risk of infection. It can also reduce financial stress in the growing population with end stage renal disease. However, PD has limitations, mainly technique failures. Of these, catheterrelated infection is a major cause of catheter failure in PD. We reviewed the medical records of 986 PD patients from 2008 to 2018 at our hospital. The patients with intractable tunnel and exit site infection received exteriorization of the outer cuff and cuff shaving. The favourable outcomes observed recommend this treatment for PD patients whose catheter infection is not well controlled.

BackgroundMitral regurgitation (MR) is a major contributor for heart failure (HF) and atrial fibrillation. Despite the advancement of MR surgeries, an effective medical therapy to mitigate MR progression is lacking. Sodium glucose cotransporter 2 inhibitors, a new class of antidiabetic drugs, has shown measurable benefits in reduction of HF hospitalization and cardiovascular mortality but the mechanism is unclear. We hypothesized that dapagliflozin (DAPA), a sodium glucose cotransporter 2 inhibitor, can improve cardiac hemodynamics in MR‐induced HF.Methods and ResultsUsing a novel, mini‐invasive technique, we established a MR model in rats, in which MR induced left heart dilatation and functional decline. Half of the rats were randomized to be administered with DAPA at 10 mg/kg per day for 6 weeks. After evaluation of electrocardiography and echocardiography, hemodynamic studies were performed, followed by postmortem tissue analyses. Results showed that DAPA partially rescued MR‐induced impairment including partial restoration of left ventricular ejection fraction and end‐systolic pressure volume relationship. Despite no significant changes in electrocardiography at rest, rats treated with DAPA exhibited lower inducibility and decreased duration of pacing‐induced atrial fibrillation. DAPA also significantly attenuated cardiac fibrosis, cardiac expression of apoptosis, and endoplasmic reticulum stress‐associated proteins.ConclusionsDAPA was able to suppress cardiac fibrosis and endoplasmic reticulum stress and improve hemodynamics in an MR‐induced HF rat model. The demonstrated DAPA effect on the heart and its association with key molecular contributors in eliciting its cardio‐protective function, provides a plausible point of DAPA as a potential strategy for MR‐induced HF.

IntroductionThis study was aimed at analyzing, modeling, and comparing the risk factors of diabetic retinopathy (DR) among type 2 diabetes mellitus (DM) patients with and without metabolic syndrome (MS).Material and methodsA cross-sectional study from July 2017 to July 2019 was performed by tracing type 2 DM patients who received treatment at an out-patient clinic and a mydriatic examination by an ophthalmologist in a single institute in south Taiwan. A total of 802 patients without DR were recruited and divided into two groups based on whether they had MS for this study. We analyzed the impact of DR based on the potential and related factors of these two groups.ResultsThe sample consisted of 802 patients; 282 patients did not have MS, and 520 did. A comparison of the risk factors of DR among the patients with and without MS revealed that the level of glycated hemoglobin (HbA1c) was a co-risk factor of DR. However, female sex, betel quid chewing, family history of DM, and higher total cholesterol were found to be risk factors of DR among the patients who had MS. Betel quid chewing, especially, could exacerbate the disease condition of DM and elevate the risk of DR.ConclusionsOf those risk factors, betel quid chewing may be the main reason for DM deterioration and raised risk of DR. Hence, we recommend that the chewing of betel quid should be avoided to prevent DR.

Taiwan has been an aged society since March 2018, and the elderly population suffer from multiple comorbidities and long duration of disability. Therefore, the service of discharge planning of long-term care 2.0 is an important stage before patients go back to the community. Strengthening the sensitivity when identifying predisabled patients is a principal development of discharge planning. In the current study, we analyzed the characteristics and predictive factors of patients who used the service of long-term care 2.0 from the perspective of discharge planning. In this retrospective study, we included patients who received the discharge planning service in a hospital located in southern Hualien during November 2017 to October 2018. The data were collected and classified as predisposing factors, enabling factors, and need factors according to the analysis architecture of the Andersen Behavioral Model. There were 280 valid patients included in this current study, age, medical accessibility, possession of a disability card, and cerebrovascular diseases, cardiovascular diseases, and diabetes mellitus were the vital factors which influenced the coherence and cohesion between discharge planning and the service of long-term care 2.0. Among them, the most influencing factor was age. We hope that the current study will make policymakers in hospitals pay attention to the usage of the discharge planning service to link long-term care 2.0 and effectively promote the usage of long-term care 2.0.

In this work, we study the problem of federated learning (FL), where distributed users aim to jointly train a machine learning model with the help of a parameter server (PS). In each iteration of FL, users compute local gradients, followed by transmission of the quantized gradients for subsequent aggregation and model updates at PS. One of the challenges of FL is that of communication overhead due to FL’s iterative nature and large model sizes. One recent direction to alleviate communication bottleneck in FL is to let users communicate simultaneously over a multiple access channel (MAC), possibly making better use of the communication resources.In this paper, we consider the problem of FL over a MAC. We focus on the design of digital gradient transmission schemes over a MAC, where gradients at each user are first quantized, and then transmitted over a MAC to be decoded individually at the PS. When designing digital FL schemes over MACs, there are new opportunities to assign different amount of resources (e.g., rate or bandwidth) to different users based on a) the informativeness of the gradients at users, and b) the underlying channel conditions. We propose a stochastic gradient quantization scheme, where the quantization parameters are optimized based on the capacity region of the MAC. We show that such channel aware quantization} for FL outperforms uniform quantization, particularly when users experience different channel conditions, and when have gradients with varying levels of informativeness.

Despite no significant differences of growth differentiation factor-15 expressions in peripheral, right atrial, and right ventricular blood, in the pulmonary arterial blood, there was a significantly high level of growth differentiation factor-15 in Group I pulmonary arterial hypertension patients subsequently developing heart failure. During right heart catheterization, collecting pulmonary blood samples is suggested to measure growth differentiation factor-15.

The causes of early bioprosthesis failure include infective endocarditis, pannus formation, and structural valve deterioration. We reported a patient who suffered from early mitral bioprosthesis failure due to leaflets restricted by the subvalvular apparatus and early pannus formation. In patients with symptoms relapse and mitral regurgitation recurrence early after mitral valve replacement, early pannus formation needs to be anticipated, and surgical intervention should be performed if symptoms persist after medical treatment.

Background Extrinsic compression of left atrium (LA) due to esophageal achalasia is uncommon. Patients might present with dysphagia, dyspnea, and even hemodynamic compromise. Prompt detection with thorough differential diagnosis is crucial for subsequent management. We presented a case with LA compression by esophageal achalasia, and literature review regarding the clinical manifestation, diagnosis, and treatment strategy was performed to provide an updating knowledge of the disease.Case presentation A 59-year-old relatively healthy man presented with dysphagia accompanied by chest tightness and breathlessness after a large meal. His chest X-ray film disclosed a widened mediastinum. The barium swallow esophagogram revealed contrast pooling at the esophagogastric junction with a bird beak shape. Meanwhile, the transthoracic echocardiogram showed a round-shaped, well bordered, hyperechogenic, and heterogeneous mass (5.1 cm x 3.8 cm in size) compressing the LA irrespective of the systolic or diastolic phase. A chest contrast-enhanced computed tomography scan showed diffuse esophageal dilatation with a smoothly thickening wall aligned compressing the LA. Due to the abovementioned image findings, extrinsic compression of LA by esophageal achalasia was diagnosed.ConclusionLA compression due to esophageal achalasia is not common. Remarkably, given a patient presenting dysphagia and concurrent dyspnea after meals, the clinicians should keep this differential diagnosis in mind. Echocardiography and esophagography are useful to ensure the diagnosis promptly.

Background: Cancer patients with diabetes have an increasing risk of Dox-induced cardiotoxicity. Despite previous studies reporting benefits of dapagliflozin on the cardiovascular system, it remains unknown whether dapagliflozin has a cardioprotective effect in cancer patients with diabetes receiving Dox therapy. The purpose of this study was to investigate the potential of dapagliflozin for preventing doxorubicin (Dox)-induced cardiotoxicity.Methods: Using Taiwan National Health Insurance Database, the incidence of heart failure of cancer patients with or without diabetes was investigated. Streptozotocin (STZ)-induced diabetic rats were pretreated with oral dapagliflozin (10 mg/kg/day) for 6 weeks followed by Dox (5 mg/kg/week) for 4 weeks via intraperitoneal injection. Sequential echocardiography was applied to assess cardiac function. For in vitro analysis, cardiomyocytes cultured in high glucose (30 mM) were treated with dapagliflozin at 10 M and subsequently exposed to Dox at 1 M. Apoptosis and endoplasmic reticulum (ER) stress-related protein expression were measured by immunohistochemistry and Western blotting.Results: Among the studied patients, those with diabetes had a higher risk of major adverse cardiovascular events including the development of heart failure. In diabetic rats, dapagliflozin reduced cardiac fibrosis and significantly improved cardiac function. Dapagliflozin effectively inhibited Dox-induced apoptosis and reactive oxygen species in cardiomyocytes under high glucose. Mechanistically, we showed that dapagliflozin decreased the cardiac expression of Bax and cleaved caspase 3 but increased Bcl-2. Dapagliflozin also significantly reduced ER stress-associated proteins including GRP78, PERK, eIF-2, ATF-4, and CHOP. Conclusions: Our study revealed for the first time that dapagliflozin mitigated Dox-induced cardiomyocyte apoptosis in diabetes via inhibiting ER stress. These results indicate that dapagliflozin could be useful for preventing cardiotoxicity in diabetic cancer patients receiving Dox treatment.

Background Arterial thrombosis is initiated by atherosclerotic plaque damage, prothrombotic material release and platelet aggregation. Platelets are primary mediators involved in thrombosis and cooperate with vascular and immune cells. Objective Herein, we investigated how activated platelets interacted with monocytes in atherothrombosis. Methods and Results We collected patients' blood from coronary arteries during percutaneous coronary intervention and measured platelet activity. Platelets from coronary arteries had higher pseudopodium expression and activity in patients with acute coronary syndrome (ACS). Ribosome profiling of platelets from coronary blood mapped a vigorous upregulation of Rho GTPases and their downstream effectors. RhoA activated downstream Rho-associated coiled-coil containing protein kinase (ROCK), and ROCK increased surface P-selectin in coronary blood platelets. The interaction between platelets and monocytes was observed in vitro, and was found in ruptured coronary plaques of ACS. Further we found that activated platelets promoted monocytes transmigration, which could be suppressed in the presence of ROCK inhibitors. The increased surface P-selectin on thrombin-induced platelets interacted with monocytes to upregulate monocyte chemokine receptor 2 (CCR2) expression via the ROCK pathway. The expression of CCR2 was higher in monocyte–platelet aggregates than in monocytes without platelets. Finally, using the Asian Screening Array BeadChip, we identified single-nucleotide polymorphism (SNP) associated with cardiovascular events. Notably, patients having homozygous major alleles of the RHOA SNP rs11706370 presented with higher risks of cardiovascular events. Conclusion Through ROCK-activated cytoskeleton remodeling and P-selectin expression, platelets were recruited and interacted synergistically with high CCR2-expressing monocytes to induce thromboinflammation in atherothrombosis.

Heart failure (HF) with mid-range ejection fraction (HFmrEF) is defined as HF with a left ventricular (LV) ejection fraction (LVEF) of 41-49%. However, the change in LV function and the subsequent prognosis in these patients remain unclear. We aimed to investigate whether LV global longitudinal strain (LV GLS) could differentiate the changes in LVEF and predict the clinical outcomes in patients with HFmrEF.According to the changes in LVEF on follow-up echocardiography, 273 outpatients with HFmrEF were divided into 3 groups: HFwEF (HF with worse EF:40%), HFsEF (HF with similar EF: 40-49%), and HFrecEF (HF with recovered EF:50%). Further, the LV GLS at diagnosis was evaluated.The average follow-up duration was 31 months. Among patients with HFmrEF, the more impaired the LV GLS at baseline, the higher probability of HFwEF development. In comparison with patients with HFwEF and HFsEF, those with HFrecEF had a lower risk of hospitalization for HF. At a cut-off value of -11%, LV GLS differentiated the subsequent risk of cardiovascular death in patients with HFmrEF. In Cox regression, patients with LV GLS-11% had a high risk of cardiovascular death.In patients with HFmrEF, LV GLS is associated with LVEF changes and subsequent cardiovascular death. Patients with HFrecEF had a lower risk of hospitalization for HF.

The pandemic of coronavirus disease 2019 (COVID-19) caused by the newly discovered virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had been noticed to have high morbidity and mortality. Apart from pneumonia, COVID-19 can also cause damage to the cardiovascular system, and co-occurring with cardiovascular injury leads to a poorer prognosis. Besides, amid the pandemic of COVID-19, the management of critical cardiovascular events needs to further account for the highly infectious coronavirus, prompt and optimal treatments, clinician's safety, and healthcare provider's capacity. This review article aims to provide more comprehensive and appropriate guidance for the management of critical cardiovascular disease, including ST-segment elevation myocardial infarction (STEMI), non-STEMI acute coronary syndrome, cardiogenic shock, acute heart failure, cardiopulmonary resuscitation, and advanced care planning, during the COVID-19 epidemic.

Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). COVID-19 significantly affects multiple systems including the cardiovascular system. Most importantly, in addition to the direct injury from the virus per se, the subsequent cytokine storm, an overproduction of immune cells and their activating compounds, causes devastating damage. To date, emerging anti-SARS-CoV-2 treatments are warranted to control epidemics. Several candidate drugs have been screened and are currently under investigation. These primarily include antiviral regimens and immunomodulatory regimens. However, beyond the anti-SARS-CoV-2 effects, these drugs may also have risks to the cardiovascular system, especially altering cardiac conduction. Herein, we review the cardiovascular risks of potential anti-COVID-19 drugs.

ObjectiveVaricose veins (VVs) are common and although considered benign may cause morbidity. However, the association between VV severity and cardiovascular and mortality risks remains unknown. The aim of this study was to investigate the factors associated with overall mortality in patients with VV.MethodsA total of 4644 patients with newly diagnosed VV between 1999 and 2013 were identified from Taiwan’s National Health Insurance Database. VV severity was classified from grade 1 to 3 according to the presentation of ulcers or inflammation. Moreover, 9497, 2541 and 5722 age-matched, sex-matched and chronic cardiovascular risk factor-matched controls, as assessed based on propensity score, were separately selected for three grading VV groups. Enrolled patients were analysed using conditional Cox proportional hazards regression analysis to estimate risk of mortality and major adverse cardiovascular events (MACEs) in the VV and control groups.ResultsMost patients with VV were free from systemic disease. However, compared with matched controls, patients with VV showed a 1.37 times increased risk of mortality (95% CI 1.19 to 1.57; pConclusionsThis nationwide cohort study demonstrated that patients with VV are at a risk of cardiovascular events and mortality. Our findings suggest that presence of VV warrants close attention in terms of prognosis and treatment.

Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. SARS-CoV-2 caused COVID-19 has reached a pandemic level. COVID-19 can significantly affect patients’ cardiovascular systems. First, those with COVID-19 and preexisting cardiovascular disease have an increased risk of severe disease and death. Mortality from COVID-19 is strongly associated with cardiovascular disease, diabetes, and hypertension. Second, therapies under investigation for COVID-19 may have cardiovascular side effects of arrhythmia. Third, COVID-19 is associated with multiple direct and indirect cardiovascular complications. Associated with a high inflammatory burden related to cytokine release, COVID-19 can induce vascular inflammation, acute myocardial injury, myocarditis, arrhythmias, venous thromboembolism, metabolic syndrome and Kawasaki disease. Understanding the effects of COVID-19 on the cardiovascular system is essential for providing comprehensive medical care for cardiac and/or COVID-19 patients. We hereby review the literature on COVID-19 regarding cardiovascular virus involvement., Graphical abstract Image, graphical abstract

With the advancement of computed tomography pulmonary angiography, differentiating between acute and chronic thrombus in pulmonary embolism has become more feasible. However, whether pulmonary embolism with chronic thrombus contributes to a higher mortality than pulmonary embolism with acute thrombus remains undetermined. Additionally, the clinical features of patients with chronic thrombus are largely unknown. Herein, we aimed to investigate the incidence and outcomes of patients with pulmonary embolism and chronic thrombus. This retrospective study included patients with pulmonary embolism from 2008 to 2016 at National Cheng Kung University Hospital. After excluding patients with tumor emboli or other etiologies and a lack of computed tomography images, we identified 205 patients with acute thrombus and 58 patients with chronic thrombus. Patients with chronic thrombus initially presented mainly with dyspnea, and the etiology was not related to recent surgery. Patients with chronic thrombus had a significantly higher incidence of elevated right ventricular systolic pressure detected by echocardiography and a higher incidence of subsequent events due to residual pulmonary embolism. Despite no differences in clinically recurrent pulmonary embolism, patients with chronic thrombus presented with a higher risk of all-cause and pulmonary embolism-related mortality than patients with acute thrombus. Chronic thrombus (hazard ratio: 2.03, p = 0.03), simplified pulmonary embolism severity index, anticoagulant use, and body mass index were the independent factors for all-cause mortality. Our findings suggest that using computed tomography pulmonary angiography for identifying patients with pulmonary embolism and chronic thrombus, which was associated with a higher risk of mortality, is pivotal for early intervention in addition to anticoagulant use.

Objective Bone marrow fluid (BMF) consists of various components that establishes a microenvironment for cell differentiation and remodeling. MicroRNA-21 (miR-21) levels have recently emerged as novel biomarkers for different diseases. However, the conventional RNU6B (U6), used as the reference for intracellular miRNA, may not be appropriate for the normalization of circulating miRNAs. Methods We measured the levels of U6, spiked-in RNA, and miR-21 in the BMF of 13 healthy controls and 37 patients with hematological disorders to investigate the reliability of either U6 or spike-in RNA as an endogenous reference and also to study the correlation between miR-21, hematological disorders and mortality. Results Notably, the levels of U6 demonstrated a high variability in BMF of healthy controls and patients. In contrast, the levels of spiked-in RNA displayed a significantly higher stability in both cohorts. Compared with controls, the levels of miR-21 were significantly upregulated in BMF of patients with leukemia but not lymphoma. Also, using 21 as the cut-off value of miR-21, it differentiated the mortality of patients with hematologic disorders. Conclusions Collectively, using spiked-in RNA as a reference the upregulated miR-21 levels in BMF could be an indicator of the diagnosis of leukemia and a predictor of mortality.

To date, cardiac dysfunction after traumatic brain injury (TBI) has not been consistent. In this study, we hypothesized that TBI may play a role in the development of new-onset cardiac dysfunction in healthy experimental rats. Anesthetized healthy male Sprague–Dawley rats were divided into two groups: a sham-operated control group and a TBI group. The brain was injured with 2.4 atm percussion via a fluid percussion injury model. During the 120 min after TBI, we continuously measured brain parameters, including intracranial pressure (ICP) and cerebral perfusion pressure (CPP), and cardiac parameters, such as heart rate (HR), inter-ventricular septum dimension (IVSD), left ventricular internal dimension diastole (LVIDd), end-diastolic volume (EDV), ejection fraction (EF), fractional shortening (FS), and LV mass diastole (LVd mass) by cardiac echo. On days 1, 3, 7, and 14 after TBI, the brain damage volume was evaluated with triphenyltetrazolium chloride; the physiological parameters of the heart, including HR, IVSd, LVIDd, EDV, EF, FS, and LVd mass, were evaluated with cardiac echo; the morphology of cardiomyocytes was examined by hematoxylin and eosin (HE) and Masson trichrome staining; and the biomarkers of cardiac injury troponin I and B-type natriuretic peptide (BNP) were also examined. Compared to sham-operated controls, the TBI groups had higher ICP, lower CPP, and higher brain neuronal apoptosis and infarction contusion volume. The impact of TBI on heart function showed hyperdynamic response trends in IVSd, LVIDd, EDV, EF, FS, and LVd mass within 30 min after TBI; however, EF and FS exhibited eventual decreasing trends. Simultaneously, the values of the biomarkers troponin I and BNP were within normal limits, and HE and Mass trichrome staining revealed no significant differences between the sham-operated control group and the TBI group. Our results suggest that TBI due to 2.4 atm fluid percussion injury in healthy experimental rats may cause significant damage to the brain and affect the heart function as investigated by cardiac echo but not as investigated by HE and Masson trichrome stainings or troponin I and BNP evaluation.

Background: General medicine practices in England are required to provide services from 8am to 8pm on weekdays and to also open on Saturdays and Sundays. Internationally, however, the literature regarding the temporal availability of primary health care on national levels is scarce. Methods: To provide such information regarding Taiwan, in this study, all family medicine clinics within Taiwan's National Health Insurance system were stratified by urbanization level, and the opening hours of the clinics were then analyzed. The opening hours of the clinics were downloaded and the data were extracted cross-sectionally in July 2015. For each clinic, the number of open sessions (in terms of morning, afternoon, and evening sessions) per week was calculated. For each urbanization level, the opening ratios for out-of-hours services and for seven-day services were also analyzed. Results: Among 1621 family medicine clinics, 835 were located in urban areas, 563 were suburban, and 223 were rural. The average numbers of open sessions per week among urban and suburban clinics were higher than among rural clinic (15.7 ± 3.7 and 15.8 ± 3.7 vs. 14.4 ± 4.0). Urban and suburban clinics also had higher opening ratios on weekday evenings and on weekends than rural clinics. Only 53 (3.3%) of all the clinics (29 urban clinics, 18 suburban clinics, and 7 rural clinics) remained open for all 21 sessions of a week. Conclusion: The great majority of family medicine clinics in Taiwan voluntarily offered out-of-hours services, but only a small minority remained open in all 21 sessions of a week. Keywords: General practice, National health insurance, Primary health care, Schedules, Taiwan

East Asians are reportedly at high risk of anticoagulant-related bleeding; therefore, some physicians prefer to prescribe low-dose direct oral anticoagulants (DOACs). Little is known about the therapeutic effectiveness and safety of off-label reduced-dose apixaban in East Asians with nonvalvular atrial fibrillation (AF). We aimed to investigate the effectiveness and safety of off-label reduced-dose apixaban in Taiwanese patients with nonvalvular AF.This retrospective cohort study enrolled 1073 patients with nonvalvular AF who took apixaban between July 2014 and October 2018 from 4 medical centers in southern Taiwan. The primary outcomes included thromboembolic events (stroke/transient ischemic attack or systemic embolism), major bleeding, and all-cause mortality.Among all patients, 826 (77%) patients were classified as the "per-label adequate-dose" treatment group (i.e., consistent with the Food and Drug Administration label recommendations) while 247 (23%) patients were the "off-label reduced-dose" treatment group. The mean follow-up period was 17.5 ± 13 months. The "off-label reduced-dose" group did not have a lower major bleeding rate than the "per-label adequate-dose" group (4.8% vs 3.8%, adjusted hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.69-2.09), but had a nonsignificantly higher incidence of thromboembolic events (4.23% vs 3.05%, adjusted HR: 1.29, 95% CI: 0.71-2.34).An off-label reduced-dose apixaban treatment strategy may not provide incremental benefits or safety for Taiwanese patients with nonvalvular AF.

Objective Obstetrician–gynecologists are the main providers of women's healthcare. However, workforce shortages and excessive workloads among these providers have been encountered in many countries. While most past studies on this subject have investigated the spatial distribution of obstetrics–gynecology clinics, few have focused on their temporal availability, especially on the national level. Materials and methods The weekly opening time schedules (divided into morning, afternoon, and evening sessions) of all obstetrics–gynecology clinics in Taiwan were extracted from the web site of Taiwan's National Health Insurance Administration in July 2015. The numbers of open sessions were then analyzed and stratified by urbanization level and practice type. Results Among 742 obstetrics–gynecology clinics in Taiwan, 521 were located in urban areas, 194 in suburban areas, and 27 in rural areas. The numbers of open sessions per week in suburban areas were higher than those in urban and rural areas (16.7 ± 2.6 vs. 15.9 ± 3.1 and 15.9 ± 2.7). Group practices had more open sessions per week than solo practices (16.8 ± 2.8 vs. 15.8 ± 3.0). With respect to after-hours services in rural areas, only two rural obstetrics–gynecology clinics remained open on Sunday mornings, while none remained open on Sunday afternoons and evenings. Conclusion Obstetrics–gynecology clinics in Taiwan offered great temporal availability. In addition to the remarkable urban–rural disparity in the distribution of obstetrics–gynecology clinics, the availability of services on Sundays in rural areas demands special attention.

Objective High-sensitivity troponin (hs-Tn) assays need to be applied appropriately to improve diagnosis and patient outcomes in acute coronary syndromes (ACS). Methods Experts from Asia Pacific convened in 2015 to provide data-driven consensus-based, region-specific recommendations and develop an algorithm for the appropriate incorporation of this assay into the ACS assessment and treatment pathway. Results Nine recommendations were developed by the expert panel: (1) troponin is the preferred cardiac biomarker for diagnostic assessment of ACS and is indicated for patients with symptoms of possible ACS; (2) hs-Tn assays are recommended; (3) serial testing is required for all patients; (4) testing should be performed at presentation and 3 hours later; (5) gender-specific cut-off values should be used for hs-Tn I assays; (6) hs-Tn I level >10 times the upper limit of normal should be considered to ‘rule in’ a diagnosis of ACS; (7) dynamic change >50% in hs-Tn I level from presentation to 3-hour retest identifies patients at high risk for ACS; (8) where only point-of-care testing is available, patients with elevated readings should be considered at high risk, while patients with low/undetectable readings should be retested after 6 hours or sent for laboratory testing and (9) regular education on the appropriate use of troponin tests is essential. Conclusions We propose an algorithm that will potentially reduce delays in discharge by the accurate ‘rule out’ of non-ACS patients within 3 hours. Appropriate research should be undertaken to ensure the efficacy and safety of the algorithm in clinical practice, with the long-term goal of improvement of care of patients with ACS in Asia Pacific.

The authors designed an interactive telecare system (ITCS) enhanced by Internet of Things (IoT) technology that enables direct communication between patients' medical devices and caregivers' smartphones to improve the quality of care for chronically ill patients. This system can remotely activate hardware components of medical devices in real time to access current information and smartphones via a telecare application. A case study was constructed with 2.5G blood glucose monitors (BGMs) integrated with a cloud platform and with Android and iOS telecare applications. Overseas medical institutions have confirmed the system's potential value in chronic-illness treatment regimens and have provided useful feedback.

Chronic thromboembolic pulmonary hypertension (CTEPH), a late complication of pulmonary embolism (PE), is associated with high mortality. However, whether the right ventricular (RV) echocardiographic parameters can predict – in the short- and long-term – the development of CTEPH and mortality after PE remains unknown. Herein, we aim to investigate the incidence of CTEPH after acute PE and to evaluate the risk factors of CTEPH. In this retrospective cohort, patients with PE were followed for 10 years for the onset of CTEPH. The screening was initially conducted through echocardiography and confirmed by right heart catheterization. Also, transient and permanent risk factors were identified. Among 358 patients with PE, 8 patients (4%) were subsequently diagnosed with CTEPH at a median time of 36 months and 47 died during the follow-up period. Notably, both short- and long-term RV dilatation, hypertrophy, and increased pulmonary pressure increased the incidence of CTEPH. However, RV echocardiographic parameters failed to differentiate survivors from non-survivors. Instead, malignancy, respiratory, or chronic heart failure was strongly associated with post PE mortality in the multivariable analysis. According to our findings, post PE screening of CTEPH may facilitate early diagnosis and intervention for patients at high risk of developing CTEPH. Also, RV echocardiographic parameters are associated with subsequent CTEPH, but mortality is mainly dependent on underlying comorbidities.

Background: How sex and age influence post-myocardial infarction (post-MI) outcomes remains unclear. This study evaluated the influence of sex and age on drug therapy, echocardiographic parameters, and outcomes in post-MI patients undergoing percutaneous coronary intervention (PCI). Methods: We retrospectively enrolled 643 patients with first acute MI who underwent successful PCI and two echocardiographic examinations within 1 year after MI. Clinical characteristics and 4-year follow-up outcomes were compared between sexes and age groups. Primary endpoints were cardiovascular mortality and hospitalization for heart failure (HF). Results: Compared with males, female patients with MI, particularly older females, had more systemic diseases. Younger females received fewer guideline-directed therapies. Older patients presented with higher left ventricular volume and mass index but no significant differences in left ventricular ejection fraction. The Kaplan–Meier analysis revealed increased mortality in both younger and older females. Elderly patients, particularly older females, exhibited significantly higher post-MI HF incidence but no difference in recurrent MI, ventricular arrhythmia, or revascularization. Conclusions: In MI patients receiving PCI, outcome differences between sexes are age-dependent. Age influences outcome more heavily in females than in males. Females are likely to exhibit worse overall survival, and older females are at higher risk of post-MI HF. Keywords: MI, Age, Gender, Cardiac structure

OBJECTIVE Atrial fibrillation (AF) is the most common cardiac complication of thyrotoxicosis and is strongly implicated in thromboembolic events. However, the incidence of stroke in thyrotoxic AF remains unclear. Herein, we aimed to investigate the risks of mortality and ischaemic stroke between patients with thyrotoxic AF and nonthyrotoxic AF. DESIGNS AND METHODS From Taiwan's National Health Insurance Research Database, 1868 patients with the concomitant diagnoses of AF and thyrotoxicosis identified between 2001 and 2010 were compared to 7472 patients with nonthyrotoxic AF using propensity score matching for age, sex and comorbidities. RESULTS There was no significant difference in either CHA2 DS2 -VASc score or anticoagulant usage between the groups. Alternatively, the thyrotoxic group contained more β-blocker/digoxin users, whereas the nonthyrotoxic group contained more statin users. Patients with thyrotoxic AF exhibited lower risks of all-cause mortality (HR: 0.66, CI: 0.59-0.73, P