Variations in the sleep-related breathing disorder index on polysomnography between men with HIV and controls: a matched case-control study.

BACKGROUND: Both sleep-related breathing disorders (SRBDs) and HIV infection can interfere with normal sleep architecture, and also cause physical and psychological distress. We aimed to understand the differences in the obstructive patterns, sleep architecture, physical and psychological distress when compared between people living with HIV (PLWH) and matched the severity of SRBDs controls. METHODS: A comparative study using matched case-control design was conducted. Men with HIV infection (case group) were enrolled from 2016 to 2019. A control group with HIV seronegative men were matched for SRBDs severity, and were selected from sleep medicine center database for comparison. RESULTS: The mean age of the 108 men (including 54 cases and 54 matched controls) was 33.75 years. Central-apnea index (CI) was higher in the case group rather than matched controls (mean CI, 0.34 vs. 0.17, p = 0.049). PLWH had a lower mean percentage of stage 3 sleep (10.26% vs. 13.94%, p = 0.034) and a higher percentage of rapid eye movement sleep (20.59% vs. 17.85%, p = 0.011) compared to matched controls. Nocturnal enuresis and sleepiness causing traffic accidents were more frequent complaint in PLWH compared to controls. CONCLUSIONS: Early detected SRBDs and subtypes in PLWH to begin treatment for the underlying cause could reduce the risk of sleepiness-related traffic accidents.

Assessing the diversity and determinants of health-related quality of life measures in patients with acute heart failure.

AIMS: Heart failure with reduced ejection fraction (HFrEF) significantly impacts health-related quality of life (HR-QoL). Existing HR-QoL questionnaires can show inconsistencies, potentially misrepresenting patient self-reports. This study examines the variation in HR-QoL measurement tools for HFrEF patients, identifying related determinants. METHODS AND RESULTS: We retrospectively analysed 134 hospitalized patients with acute decompensated HFrEF at a Taiwanese tertiary centre's Heart Failure Post-Acute-Care (HF-PAC) programme. Participants completed the EuroQol-5 dimension (EQ-5D) questionnaire, the EQ-5D visual analogue scale (VAS), and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Utility values were obtained from the EQ-5D questionnaire. Demographic features were depicted using descriptive statistics, while multivariate regression was used to ascertain relationships between HR-QoL measurements and determinants. Average scores for EQ-5D, MLHFQ, EQ-5D utility, and VAS were 6.1 ± 1.6, 21.8 ± 21.3, 81.7 ± 27.0, and 59.5 ± 14.6, respectively. Significant correlations were observed among the three tools. The New York Heart Association functional class showed a notable association with all tool scores. Other associations encompassed EQ-5D with coronary artery disease, mineralocorticoid receptor antagonists, and the 6 min walk test; EQ-5D VAS with chronic kidney disease; and MLHFQ with age. CONCLUSIONS: This study illuminates the variance in HR-QoL measurement tools for Taiwanese HFrEF patients. Using a range of these tools is beneficial in unveiling diverse determinants and approaching comprehensive patient-centred care. However, for a more precise HR-QoL assessment in Taiwanese HFrEF patients, recalibrating the EQ-5D-derived utility scores might be necessary, emphasizing the importance of patient-specific considerations within the HF-PAC programme.

Utility of the ACD-GENE-CLI Score in Asian Patients with Critical Limb Ischemia Undergoing Endovascular Interventions.

AIMS: Critical limb ischemia (CLI) is an emerging public health threat and lacks a reliable score for predicting the outcomes. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD-GENE) risk score helps identify patients with coronary artery disease who have cytochrome P450 2C19 (CYP2C19) polymorphism-related drug resistance and are at risk for cardiovascular adverse events. However, its application to CLI remains unknown. In this study, we aim to validate a modified ACD-GENE-CLI score to improve the prediction of major adverse limb events (MALEs) in patients with CLI receiving clopidogrel. METHODS: Patients with CLI receiving clopidogrel post-endovascular intervention were enrolled prospectively in two medical centers. Amputation and revascularization as MALEs were regarded as the outcomes. RESULTS: A total of 473 patients were recruited, with a mean follow-up duration of 25 months. Except for obesity, old age, diabetes, chronic kidney disease (CKD), and CYP2C19 polymorphisms were significantly associated with MALEs. Using bootstrap regression analysis, we established a modified risk score (ACD-GENE-CLI) that included old age (≥ 65 years), diabetes, CKD, and CYP2C19 polymorphisms. At a cutoff value of 8, the ACD-GENE-CLI score was superior to the CYP2C19 deficiency only, and the conventional ABCD-GENE score in predicting MALEs (area under the curve: 0.69 vs. 0.59 vs. 0.67, p=0.01). The diagnostic ability of the ACD-GENE-CLI score was consistent in the external validation. Also, Kaplan-Meier curves showed that in CYP2C19 deficiency, the ABCD-GENE and ACD-GENE-CLI scores could all differentiate patients with CLI who are free from MALEs. CONCLUSIONS: The modified ACD-GENE-CLI score could differentiate patients with CLI receiving clopidogrel who are at risk of MALEs. Further studies are required to generalize the utility of the score.

Assessment of subclinical cardiac dysfunction by speckle-tracking echocardiography among people living with human immunodeficiency virus.

Background: People living with HIV (PLWH) have an increased risk of developing cardiovascular diseases (CVD). As speckle-tracking echocardiography (STE) has been used to detect subclinical myocardial abnormalities, this study aims to detect early cardiac impairment among Asian PLWH using STE and to investigate the associated risk factors. Methods: We consecutively recruited asymptomatic PLWH without previous CVD from a medical center of Taiwan, and their cardiac function was evaluated by conventional echocardiogram and STE. Enrolled PLWH were classified as antiretroviral therapy (ART)-experienced and ART-naive, and multivariable regressions were used to assess the association between myocardial strain and risk factors including traditional CVD and HIV-associated factors. Results: A total of 181 PLWH (mean age: 36.4 ± 11.4 years, 173 males) were recruited and conventional echocardiogram parameters were within normal ranges. Decreased myocardial strain across the myocardium was found, with a mean left ventricular (LV) global longitudinal strain of -18.7 ± 2.9%. The LV strain in the ART-experienced group (-19.0 ± 2.9%) was significantly better than the ART-naive group (-17.9 ± 2.8%), despite a younger age and lesser CVD risk factors in the ART-naive group. Hypertension [B = 1.92, 95% confidence interval (95% CI) 0.19-3.62, p = 0.029] and ART-naive with both low and high viral loads (VL) (B = 1.09, 95% CI 0.03-2.16, p = 0.047; and B = 2.00, 95% CI, 0.22-3.79, p = 0.029) were significantly associated with reduced myocardial strain. Conclusion: This is the first and largest cohort using STE to investigate myocardial strain in Asian PLWH. Our results suggest that hypertension and detectable VL are associated with impaired myocardial strain. Thus, timely ART administration with VL suppression and hypertension control are crucial in preventing CVD when making the management parallel with the improved life expectancy of PLWH on ART.

The clinical efficacy of melatonin in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

Background: The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide, with cytokine storm leading to exaggerating immune response, multi-organ dysfunction and death. Melatonin has been shown to have anti-inflammatory and immunomodulatory effects and its effect on COVID-19 clinical outcomes is controversial. This study aimed to conduct a meta-analysis to evaluate the impact of melatonin on COVID-19 patients. Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched without any language or publication year limitations from inception to 15 Nov 2022. Randomized controlled trials (RCTs) using melatonin as therapy in COVID-19 patients were included. The primary outcome was mortality, and the secondary outcomes included were the recovery rate of clinical symptoms, changes in the inflammatory markers like C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR). A random-effects model was applied for meta-analyses, and further subgroup and sensitivity analyses were also conducted. Results: A total of nine RCTs with 718 subjects were included. Five studies using melatonin with the primary outcome were analyzed, and the pooled results showed no significant difference in mortality between melatonin and control groups with high heterogeneity across studies identified (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.47-1.11, p = 0.14, I2 = 82%). However, subgroup analyses revealed statistically significant effects in patients aged under 55 years (RR 0.71, 95% CI 0.62-0.82, p < 0.01) and in patients treated for more than 10 days (RR 0.07, 95% CI 0.01-0.53, p = 0.01). The recovery rate of clinical symptoms and changes in CRP, ESR, and NLR were not statistically significant. No serious adverse effects were reported from melatonin use. Conclusion: In conclusion, based on low certainty of evidence, the study concluded that melatonin therapy does not significantly reduce mortality in COVID-19 patients, but there are possible benefits in patients under 55 years or treated for more than 10 days. With a very low certainty of evidence, we found no significant difference in the recovery rate of COVID-19 related symptoms or inflammatory markers in current studies. Further studies with larger sample sizes are warranted to determine the possible efficacy of melatonin on COVID-19 patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022351424.

Cost-effectiveness of Intensive vs Standard Blood Pressure Control Among Older Patients With Hypertension.

Importance: Older patients with hypertension receiving intensive systolic blood pressure control (110-130 mm Hg) have lower incidences of cardiovascular events than those receiving standard control (130-150 mm Hg). Nevertheless, the mortality reduction is insignificant, and intensive blood pressure management results in more medical costs from treatments and subsequent adverse events. Objective: To examine the incremental lifetime outcomes, costs, and cost-effectiveness of intensive vs standard blood pressure control in older patients with hypertension from the health care payer's perspective. Design, Setting, and Participants: This economic analysis was conducted with a Markov model to examine the cost-effectiveness of intensive blood pressure management among patients aged 60 to 80 years with hypertension. Treatment outcome data from the Trial of Intensive Blood-Pressure Control in Older Patients With Hypertension (STEP trial) and different cardiovascular risk assessment models for a hypothetical cohort of STEP-eligible patients were used. Costs and utilities were obtained from published sources. The incremental cost-effectiveness ratio (ICER) against the willingness-to-pay threshold was used to evaluate whether the management was cost-effective. Extensive sensitivity, subgroup, and scenario analyses were performed to address uncertainty. The US and UK population using race-specific cardiovascular risk models were conducted in the generalizability analysis. Data for the STEP trial were collected from February 10 to March 10, 2022, and were analyzed for the present study from March 10 to May 15, 2022. Interventions: Hypertension treatments with a systolic blood pressure target of 110 to 130 mm Hg or 130 to 150 mm Hg. Main Outcomes and Measures: Incremental lifetime quality-adjusted life-years (QALYs), costs, and ICER are discounted at the given rates annually. Results: After simulating 10 000 STEP-eligible patients assumed to be 66 years of age (4650 men [46.5%] and 5350 women [53.5%]) in the model, the ICER values were ¥51 675 ($12 362) per QALY gained in China, $25 417 per QALY gained in the US, and £4679 ($7004) per QALY gained in the UK. Simulations projected that the intensive management in China being cost-effective were 94.3% and 100% below the willingness-to-pay thresholds of 1 time (¥89 300 [$21 364]/QALY) and 3 times (¥267 900 [$64 090]/QALY) the gross domestic product per capita, respectively. The US had 86.9% and 95.6% probabilities of cost-effectiveness at $50 000/QALY and $100 000/QALY, respectively, and the UK had 99.1% and 100% of probabilities of cost-effectiveness at £20 000 ($29 940)/QALY and £30 000 ($44 910)/QALY, respectively. Conclusions and Relevance: In this economic evaluation, the intensive systolic blood pressure control in older patients produced fewer cardiovascular events and had acceptable costs per QALY gained, well below the typical willingness-to-pay thresholds. The cost-effective advantages of intensive blood pressure management in older patients were consistent over various clinical scenarios across different countries.

Economic evaluation of new blood pressure target for hypertensive patients in Taiwan according to the 2022 hypertension clinical practice guidelines of the Taiwan society of cardiology: a simulation modeling study.

With the promising cardiovascular benefits in the STEP and SPRINT trials, the 2022 Taiwan's hypertension guidelines redefined the hypertension threshold as 130/80 mmHg and a universal blood-pressure target of <130/80 mmHg. This study's objective was to examine the cost-effectiveness of the intensive blood-pressure target for hypertensive patients using estimated lifetime medical costs and quality-adjusted life years (QALY) from the Taiwan national payer's perspective. We developed a lifetime Markov model comparing the intensive and conservative blood-pressure targets. Incremental cost-effectiveness ratio (ICER) against the willing-to-pay thresholds at the one-time [US$34,000(NT$1,020,000)] and three-time [US$100,000(NT$3,000,000)] gross domestic product per capita were defined as very cost-effect and only cost-effective. The cost-effectiveness in different age stratifications and cardiovascular risks treated with a more intensive target (120 mmHg) were examined in the subgroup analyses. The new blood-pressure treatment target produced more lifetime medical costs [US$31,589(NT$947,670) versus US$26,788(NT$803,640)] and QALYs (12.54 versus 12.25), and the ICER was US$16,589(NT$497,670), which was 99.1% and 100% probability of a very cost-effective and cost-effective strategy. The ICERs in all age stratifications had more than a 90% probability of being very cost-effective, and ICERs decreased with age. More intensive control in patients with high cardiovascular risks produced a lower ICER [US$14,547(NT$436,410)]. In conclusion, Taiwan's new blood-pressure treatment target can prevent more cardiovascular events with acceptable costs per QALY below the willing-to-pay thresholds. The cost-effectiveness of intensive control is consistent across different ages and more pronounced with the increase in age and cardiovascular risk.

Association of sepsis-induced cardiomyopathy and mortality: a systematic review and meta-analysis.

BACKGROUND: The implication of sepsis-induced cardiomyopathy (SIC) to prognosis is controversial, and its association with mortality at different stages remains unclear. We conducted a systematic review and meta-analysis to understand the association between SIC and mortality in septic patients. METHODS: We searched and appraised observational studies regarding the mortality related to SIC among septic patients in PubMed and Embase from inception until 8 July 2021. Outcomes comprised in-hospital and 1-month mortality. We adopted the random-effects model to examine the mortality risk ratio in patients with and without SIC. Meta-regression, subgroup, and sensitivity analyses were applied to examine the outcome's heterogeneity. RESULTS: Our results, including 20 studies and 4,410 septic patients, demonstrated that SIC was non-statistically associated with increased in-hospital mortality, compared to non-SIC (RR 1.28, [0.96-1.71]; p = 0.09), but the association was statistically significant in patients with the hospital stay lengths longer than 10 days (RR 1.40, [1.02-1.93]; p = 0.04). Besides, SIC was significantly associated with a higher risk of 1-month mortality (RR 1.47, [1.17-1.86]; p < 0.01). Among SIC patients, right ventricular dysfunction was significantly associated with increased 1-month mortality (RR 1.72, [1.27-2.34]; p < 0.01), while left ventricular dysfunction was not (RR 1.33, [0.87-2.02]; p = 0.18). CONCLUSIONS: With higher in-hospital mortality in those hospitalized longer than 10 days and 1-month mortality, our findings imply that SIC might continue influencing the host's system even after recovery from cardiomyopathy. Besides, right ventricular dysfunction might play a crucial role in SIC-related mortality, and timely biventricular assessment is vital in managing septic patients.

Recurrent thromboembolism, bleeding, and mortality in Asian patients with venous thromboembolism receiving different oral anticoagulants: A nationwide analysis.

Venous thromboembolism (VTE) is associated with a high risk of morbidity and mortality. However, data on the association between oral anticoagulants and the hazards of VTE complications in Taiwanese patients with VTE is limited. This study aimed to compare the hazards of recurrent VTE, bleeding, and mortality between patients with VTE receiving rivaroxaban, a non-vitamin K antagonist oral anticoagulant (NOAC), and those receiving heparin or low-molecular-weight heparin (LMWH) followed by warfarin. Patients with VTE treated with rivaroxaban, or heparin or LMWH followed by warfarin were enrolled from 2 million random samples from Taiwan's National Health Insurance database between 2013 and 2016. Hazards of recurrent VTE (deep vein thrombosis and pulmonary embolism), major bleeding, and mortality in rivaroxaban and warfarin users were investigated. Survival analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Users of rivaroxaban (183) and warfarin (456) were included in the study. Patients receiving rivaroxaban did not have significantly lower hazards of developing recurrent VTE (HR, 0.72 [CI, 0.37-1.37], P = .31) and mortality (HR, 0.86 [CI, 0.49-1.50], P = .59) than those receiving heparin or LMWH followed by warfarin. In addition, the hazard ratio of major bleeding was not significantly different between the 2 regimens (HR, 1.80 [CI, 0.39-8.29], P = .45). Rivaroxaban was not associated with lower risks of recurrent VTE and mortality and higher hazards of major bleeding than heparin or LMWH followed by warfarin in Taiwanese patients with VTE. Clinicians may tailor oral anticoagulants for VTE patients according to the patient's characteristics, cost-effectiveness and healthcare system policy.

Cost-Effectiveness Evaluation of Add-on Empagliflozin in Patients With Heart Failure and a Reduced Ejection Fraction From the Healthcare System's Perspective in the Asia-Pacific Region.

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.

Cost-effectiveness evaluation of add-on dapagliflozin for heart failure with reduced ejection fraction from perspective of healthcare systems in Asia-Pacific region.

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.

A Rare Cause of Left Atrium Compression.

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.

Association of adherence to antiretroviral therapy with economic burden of cardiovascular disease in HIV-infected population.

AIMS: There is a lack of studies that rigorously and systematically assess the economic burden of cardiovascular diseases (CVDs) related to the use of antiretroviral therapy (ART). We aimed to assess the association between adherence to ART and economic burden of CVDs in an HIV-infected population. METHODS: Taiwan's National Health Insurance Research Database 2000-2011 was utilized for analyzing 18,071 HIV-infected patients free of CVDs before HIV diagnosis. The level of adherence to ART was measured by the medication possession ratio (MPR). Generalized estimating equations analysis was applied to estimate the cost impact of a variety of CVDs. All costs were presented in 2018 US dollars. RESULTS: The incidence of CVDs ranged from 0.17/1000 person-years (cardiogenic shock) to 2.60/1000 person-years (ischemic heart diseases (IHDs)). The mean annual medical cost for a base-case patient without CVDs was US$3000. Having cerebrovascular diseases, myocardial infarction, heart failure, arrhythmia, and IHDs increased annual costs by 41%, 33%, 30%, 16%, and 14%, respectively. The cost impact of incident CVDs in years with high adherence to ART (MPR ≥ 0.8) was significantly lower than that in years with low adherence (MPR < 0.1) (e.g. having cerebrovascular diseases in the high- versus low-adherence years increased annual costs by 21% versus 259%, respectively). CONCLUSION: The economic burden of incident CVDs in an HIV-infected population was compelling and varied by the extent of using ART. A reduced economic impact of CVDs was found in years when patients possessed a greater adherence to ART.

Cardiovascular Complications of COVID-19 and Associated Concerns: A Review.

SARS-CoV-2 is the virus that has caused the current coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 is characterized by significantly affecting the cardiovascular system of infected patients. In addition to the direct injuries caused by the virus, the subsequent cytokine storm - an overproduction of immune cells and their activating compounds - also causes damage to the heart. The development of anti-SARS-CoV-2 treatments is necessary to control the epidemic. Despite an explosive growth in research, a comprehensive review of up-to-date information is lacking. Herein, we summarize pivotal findings regarding the epidemiology, complications, and mechanisms of, and recent therapies for, COVID-19, with special focus on its cardiovascular impacts.

A Double-Edged Sword-Cardiovascular Concerns of Potential Anti-COVID-19 Drugs.

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.

Cost-effectiveness analysis of rivaroxaban plus aspirin versus aspirin alone in secondary prevention among patients with chronic cardiovascular diseases.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Antimicrobial ability and mechanism analysis of Lactobacillus species against carbapenemase-producing Enterobacteriaceae.

BACKGROUND: This study aims to investigate the antimicrobial ability and mechanism analysis of Lactobacillus species against carbapenemase-producing Enterobacteriaceae (CPE). METHODS: Five Lactobacillus spp. strains and 18 CPE clinical isolates were collected. Their anti-CPE effects were assessed by agar well diffusion and broth microdilution assay, as well as time-kill test. Finally, the specific anti-CPE mechanism, especially for the effect of organic acids was determined using broth microdilution method. RESULTS: All of five Lactobacilli isolates displayed the potent activity against most CPE isolates with mean zones of inhibition ranging 10.2-21.1 mm. The anti-CPE activity was not affected by heating, catalase, and proteinase treatment. Under the concentration of 50% LUC0180 cell-free supernatant (CFS), lactic acid, and mix acid could totally inhibit the growth of carbapenem-resistant Klebsiella pneumoniae (CPE0011), and acetic acid could inhibit 67.8%. In contrast, succinic acid and citric acid could not inhibit the growth of CPE0011. While we decreased the concentration to 25%, only lactic acid and mix acid displayed 100% inhibition. In contrast, succinic acid, citric acid and acetic acid did not show any inhibitory effect. CONCLUSIONS: Lactobacillus strains exhibit potent anti-CPE activity, and lactic acid produced by Lactobacillus strains is the major antimicrobial mechanism.

Topical antibiotic prophylaxis for surgical wound infections in clean and clean-contaminated surgery: a systematic review and meta-analysis.

BACKGROUND: Topical antibiotics are widely prescribed as prophylaxis for surgical site infection (SSI). Despite giving high drug concentrations at local wound sites, their efficacy remains controversial. This study is a systematic review and meta-analysis designed to compare the efficacy and safety of topical antibiotics with non-antibiotic agents in preventing SSI. METHODS: Randomized controlled trials (RCTs) comparing topical antibiotics in patients with clean and clean-contaminated postsurgical wounds were included. Relevant trials published before 30 September 2020, were searched in the PubMed, Embase, and Cochrane databases, without language restrictions. The primary outcome was the incidence of SSIs, presented as the event rate. The secondary outcome was the incidence of contact dermatitis (safety outcome). Data were synthesized using the random-effects model, with the results expressed as risk ratio (RR) with 95 per cent confidence intervals (c.i.). RESULTS: Thirteen RCTs were included. The incidence of SSIs and contact dermatitis showed no significant difference between topical antibiotics and non-antibiotic agents (RR 0.89, 95 per cent c.i. 0.59 to 1.32 (P = 0.56, I2 = 48 per cent); and RR 2.79, 95 per cent c.i. 0.51 to 15.19 (P = 0.24, I2 = 0 per cent), respectively). In the subgroup analyses, a reduction in SSIs was also not observed in dermatological (RR 0.77, 95 per cent c.i. 0.39 to 1.55; P = 0.46, I2 = 65 per cent), ocular (RR 0.08, 95 per cent c.i. 0.00 to 1.52; P = 0.09), spinal (RR 1.34, 95 per cent c.i. 0.65 to 2.77; P = 0.43, I2 = 0 per cent), orthopaedic (RR 0.69, 95 per cent c.i. 0.37 to 1.29; P = 0.25, I2 = 0 per cent), or cardiothoracic surgeries (RR 1.60, 95 per cent c.i. 0.79 to 3.25; P = 0.19). CONCLUSION: Given the current evidence, the routine application of topical antibiotics to surgical wounds did not reduce the incidence of SSI. Further trials are needed to assess their effectiveness in high-risk surgeries or in selected patient groups.