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OBJECTIVE: We designed a retrospective study to evaluate the performance and outcomes of a novel iopromide-based paclitaxel-coated balloon for the treatment of chronic total occlusion of femoropopliteal arteries. METHODS: Patients with femoropopliteal chronic total occlusion (

Response to cardiovascular drugs can vary greatly between individuals, and the role of the microbiome in this variability is being increasingly appreciated. Recent evidence indicates that bacteria and other microbes are responsible for direct and indirect effects on drug efficacy and toxicity. Pharmacomicrobiomics aims to uncover variability in drug response due to microbes in the human body, which may alter drug disposition through microbial metabolism, interference by microbial metabolites, or modification of host enzymes. In this review, we present recent advances in our understanding of the interplay between microbes, host metabolism, and cardiovascular drugs. We report numerous cardiovascular drugs with evidence of, or potential for, gut-microbe interactions. However, the effects of gut microbiota on many cardiovascular drugs are yet uninvestigated. Finally, we consider potential clinical applications for the described findings.

Objective:. Cardiovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk. The effects of drugs on individual usage are also often unknown. This review aimed to examine the correlation between depression and common cardiovascular drugs, develop more potent interventions for depression in cardiovascular patients, and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression. Data sources:. The data in this review were obtained from articles included in PubMed, EMBASE, and Web of Science. Study selection:. Clinical trials, observational studies, review literature, and guidelines about depression and cardiovascular drugs were selected for the article. Results:. We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review. Statins have been proven to have antidepressant effects. Some studies believe angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARB) can exert an antidepressant influence by acting on the renin-angiotensin system, but further clinical trials are needed to confirm this. Beta-blockers have previously been associated with depression, but the current study found no significant association between beta blockers and the risk of depression. Aspirin may have antidepressant effects by suppressing the immune response, but its role as an antidepressant remains controversial. calcium channel blockers (CCBs) can regulate nerve signal transduction by adjusting calcium channels, but whether this effect is beneficial or harmful to depression remains unclear. Finally, some cases have reported that nitrates and diuretics are associated with depression, but the current clinical evidence is insufficient. Conclusions:. Statins have been proven to have antidepressant effect, and the antidepressant effects of ACEIs/ARB and aspirin are still controversial. CCBs are associated with depression, but it is unclear whether it is beneficial or harmful. No association has been found with β-blockers, diuretics, and nitrates.

Background The prognostic factors of long-term outcomes in hospitalized patients with diabetes mellitus and COVID-19 are lacking. Methods In this retrospective cohort study, we evaluated patients aged ≥ 18-years-old with the COVID-19 diagnosis who were hospitalized between Feb 20 and Oct 29, 2020, in the Sina Hospital, Tehran, Iran. 1323 patients with COVID-19 entered in the final analysis, of whom 393 (29.7%) patients had diabetes. We followed up patients for incurring in-hospital death, severe COVID-19, in-hospital complications, and 7-month all-cause mortality. By doing univariate analysis, variables with unadjusted P-value

Background: As our society ages, the incidence of chronic diseases increases, and so does drug use and polypharmacy. Aim: To evaluate the medication use behaviors of selected elderly patients who lived in Baghdad city. Methods: This cross-sectional study included 225 subjects aged >60 years who lived in Baghdad city and consumed chronically prescribed medications. Data were collected using a survey form, and the survey was conducted through face-to-face interviews. The data are presented as numbers, percentages, and averages. Results: The majority were treated through polypharmacy, using various drugs. The most commonly used drugs included those used to treat cardiovascular diseases, DM, and dyslipidemia. 74.6% did not know about the side effects of the drugs they used, and 55.6% did not read the product information leaflet (PIL) of the drugs. Also, 70.7% said that the health care personnel did not educate them about their drugs. Of the elderly who were informed about their drugs, 128 obtained the information from the physician and 91 from the pharmacist. Conclusion: The majority of the elderly subjects used more than one drug, and the main drug class used was the cardiovascular agents. they are unaware of the side effects of the prescribed agents.

While acetylcholinesterase inhibitors are used to treat a wide range of patients with Alzheimer’s disease, acetylcholinesterase inhibitor use has also been associated with a variety of cardiovascular complications, including bradycardia and syncope. Herein, we review the pathophysiology and clinical evidence for cardiovascular complications caused by acetylcholinesterase inhibitors in patients being treated for dementia and discuss options for their management.

Background: The coronavirus disease 19 (COVID-19) recently became one of the leading causes of death worldwide, similar to cardiovascular disease (CVD). Coexisting CVD may influence the prognosis of patients with COVID-19. Aims: We analyzed the impact of CVD and the use of cardiovascular drugs on the in-hospital course and mortality of patients with COVID-19. Methods: We retrospectively studied data for consecutive patients admitted to our hospital, with COVID-19 between March 6th and October 15th, 2020. Results: 1729 patients (median interquartile range age 63 [50–75] years; women 48.8%) were included. Overall, in-hospital mortality was 12.9%. The most prevalent CVD was arterial hypertension (56.1%), followed by hyperlipidemia (27.4%), diabetes mellitus (DM) (25.7%), coronary artery disease (16.8%), heart failure (HF) (10.3%), atrial fibrillation (13.5%), and stroke (8%). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) were used in 25.0% of patients, β-blockers in 40.7%, statins in 15.6%, and antiplatelet therapy in 19.9%. Age over 65 years (odds ratio [OR], 6.4; 95% CI, 4.3–9.6), male sex (OR, 1.4; 95% CI, 1.1–2.0), pre-existing DM (OR, 1.5; 95% CI, 1.1–2.1), and HF (OR, 2.3; 95% CI, 1.5–3.5) were independent predictors of in-hospital death, whereas treatment with ACEIs/ARBs (OR, 0.4; 95% CI, 0.3–0.6), β-blockers (OR, 0.6; 95% CI, 0.4–0.9), statins (OR, 0.5; 95% CI, 0.3–0.8), or antiplatelet therapy (OR, 0.6; 95% CI: 0.4–0.9) was associated with lower risk of death. Conclusions: Among cardiovascular risk factors and diseases, HF and DM appeared to increase in-hospital COVID-19 mortality, whereas the use of cardiovascular drugs was associated with lower mortality.

Medication related problems (MRPs) can be defined as an event or situation involving drug therapy that potentially interferes with desired health outcome. The aim of the study was to identify the class of drugs that are commonly causing medication related problems in elderly patients. This study was conducted in 150 patients aged over 60 years for a duration of six months. The data were collected using a patient interview form and was analysed using Microsoft Excel 2016. Out of 150 patients participated in the study, 107 patients were identified with MRPs. And a total of 196 MRPs were identified from those 107 patients. The patients who were treated with cardiovascular agents where more prone to medication related problems and was found to be 57%. They were followed by endocrine agents (33%), gastro-protectants (21%), respiratory agents (17%) & others. This study concluded that, pharmacist can be helpful in identification and prevention of MRPs leading to a better healthcare outcomes. Keywords: Medication related problem, elderly population, class of drug.

Angiotensin receptor-neprilysin inhibitors (ARNIs) are a new class of cardiovascular agents characterized by their dual action on the major regulators of the cardiovascular system, including the renin-angiotensin system (RAS) and the natriuretic peptide (NP) system. The apparent clinical benefit of one ARNI, sacubitril/valsartan, as shown in clinical trials, has positioned the drug class as a first-line therapy in patients with heart failure, particularly with reduced ejection fraction. Accumulating evidence also suggests that sacubitril/valsartan is superior to conventional RAS blockers in lowering blood pressure in patients with hypertension. To decide whether to apply an ARNI to treat hypertension clinically, it is important to understand the potential properties of the drug in modulating multiple factors inside and outside the cardiovascular system beyond its effect on reducing peripheral blood pressure. In this context, ARNIs are distinct from preexisting antihypertensive medications in terms of the multiple actions of NPs in various organs and the pharmacological potential of neprilysin inhibitors to modulate multiple cardiac and noncardiac peptides. In particular, analysis of the clinical trials of sacubitril/valsartan implies that ARNIs can provide additional clinical benefits independent of their original purpose, including alleviation of glycemic control and renal impairment in patients with heart failure. Understanding the potential mechanisms of action of ARNIs will help interpret the relevance of their additional benefits beyond lowering blood pressure in hypertension. This review summarizes the comprehensive clinical evidence and relevance of ARNIs by specifically focusing on the potential properties of this new drug class in treating patients with hypertension.

Objectives The aim of this study was to identify the patterns of medication load, its medication burden, coordination of healthcare and patient’s understanding of their conventional cardiac medications and related herbal-derived preparations. Methods The study is a mixed-method both, quantitative and qualitative approach, which involved Filipino elderly patients (n=69) enrolled in the outpatient service of the National Center for Geriatric Health, Manila. Data were gathered through face-to-face surveys and interviews using a semi-structured questionnaire. Descriptive statistics were used during data analysis. Thematic analysis was also used to emphasize patterns in the responses of the participants. Results Respondents were knowledgeable on the name (86.9%), visual characteristics (78.3%), and indication and administration of their medicine (88.4%). The frequency of their doctor’s information on the possible side effects of the medicines was noted. The almost negligible difference in the proportions of those who asserted during the information dissemination on the medication side effect by their doctors was observed ( Conclusions The majority of the elderly patients recognized the purpose and extent of medication. It was noted that pharmacists play a limited role in understanding selected Filipino elderly patients on their medication. Lack of communication between the patient and the pharmacist was noted as preliminary findings in the study. Respondents were not yet informed of the responsibility of the pharmacist to provide information regarding their medication. Integration of pharmacists’ care for geriatric health must be strengthened and highly recommended. Supervision by the healthcare professionals, particularly by the pharmacists, must be fully established.

Purpose Results of the 2020 ASHP national survey of pharmacy practice in hospital settings pertaining to pharmacy operational changes implemented in response to the coronavirus disease 2019 (COVID-19) pandemic are presented. Methods Pharmacy directors at 1,437 general and children’s medical/surgical hospitals in the United States were surveyed using a mixed-mode method of contact by email and mail. Survey completion was online. Results The response rate was 18.7%. Seventy-three percent of hospitals implemented changes to hospital units, including 46% that increased intensive care unit bed capacity; 94% made changes to pharmacy supply chain acquisition, changes to products, and/or increased inventory. Staffing changes were implemented by 69% of hospitals, with the most common being staffing reductions (55%) and salary reductions (16%). Medication-use changes were implemented by 86% of hospitals, with treatment guidelines for COVID-19 treatment (79%) and opening compassionate use or investigational drug studies (55%) being the most common. Changes in sterile compounding processes were implemented by 84% of hospitals. Personal protective equipment (PPE) shortages led to 71% of hospitals modifying PPE use standards in sterile compounding. Eighty-seven percent of hospitals changed operational activities, such as changing medication return practices (56%), medication reconciliation processes (46%), intravenous medication recycling (38%), and discharge counseling (37%). Hospitals experienced shortages of many medications, including albuterol inhalers (60%), sedatives and anesthetic agents (58%), neuromuscular blockers (43%), corticosteroids (34%), cardiovascular agents (24%), investigational agents (24%), and dialysis solutions (6%). Conclusion The pharmacy profession responded to myriad threats to operations and patient care during the COVID-19 pandemic in 2020.

Coronavirus disease 2019 (COVID-19), a mystified cryptic virus has challenged the mankind that has brought life to a standstill. Catastrophic loss of life, perplexed healthcare system and the downfall of global economy are some of the outcomes of this pandemic. Humans are raging a war with an unknown enemy. Infections, irrespective of age and gender, and more so in comorbidities are escalating at an alarming rate. Cardiovascular diseases, are the leading cause of death globally with an estimate of 31% of deaths worldwide out of which nearly 85% are due to heart attacks and stroke. Theoretically and practically, researchers have observed that persons with pre-existing cardiovascular conditions are comparatively more vulnerable to the COVID-19 infection. Moreover, they have studied the data between less severe and more severe cases, survivors and non survivors, intensive care unit (ICU) patients and non ICU patients, to analyse the relationship and the influence of COVID-19 on cardiovascular health of an individual, further the risk of susceptibility to submit to the virus. This review aims to provide a comprehensive particular on the possible effects, either direct or indirect, of COVID-19 on the cardiovascular heath of an individual.

Injury/dysfunction of the endothelium of pulmonary arteries contributes to hypoxia-induced pulmonary hypertension (HPH). We investigated whether C1q/tumor necrosis factor-related protein-9 (CTRP9), a newly identified cardiovascular agent, has protective roles in the development of HPH. HPH was induced in adult male rats by chronic hypobaric hypoxia. CTRP9 overexpression by adeno-associated virus (AAV)-CTRP9 transfection attenuated the increases in right ventricular systolic pressure, right ventricular hypertrophy index, and pulmonary arterial remodeling of rats under hypoxia. Importantly, CTRP9 overexpression improved endothelium-dependent vasodilation in pulmonary arterioles in HPH rats. CTRP9 overexpression enhanced expression of phosphorylated 5′-adenosine monophosphate-activated protein kinase (p-AMPK) and phosphorylated endothelial nitric oxide synthase (p-eNOS), and reduced phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2) expression in pulmonary microvascular endothelial cells (PMVECs) of HPH rats. In cultured PMVECs, CTRP9 not only preserved the decrease of AMPK and eNOS phosphorylation level and nitric oxide (NO) production induced by hypoxia, but also blocked the increase in hypoxia-induced ERK1/2 phosphorylation level and endothelin (ET)-1 production. Furthermore, the effects of CTRP9 were interrupted by inhibitors or knockdown of AMPK. CTRP9 enhances NO production and reduces ET-1 production by regulating AMPK activation. CTRP9 could be a target for HPH.

Amongst a wide range of biological macromolecules, saccharides exhibit the potential to be specifically recognized by cell-surface receptors and hence can be utilized as ligands in targeted drug delivery. The current study aims to use saccharides viz. Galactose, Pectin and Chitosan to improve targeting of Atenolol by oxalyl chloride mediated grafting. Conjugates were engineered by grafting Atenolol, a cardiovascular agent with the modified saccharide units. The conjugates were characterized by FTIR, DSC and 1H NMR study. Drug release analysis and cellular uptake study was carried out using H9c2 cell lines which represent that concentration of drug in cells treated with all atenolol-saccharide conjugates is enhanced by almost two-folds in comparison with cells treated with atenolol solution. Thus cell line study confers the evidence of selective cardiac delivery. No significant cytotoxicity was observed in case of all synthesized conjugates in the Brine shrimp lethality bioassay. Possible binding of the developed conjugates with the GLUT-4 receptors was assessed by in silico analysis using homology model developed by Swiss Model server. Hence it was concluded that the application of these conjugates with saccharides in selective cardiovascular drug delivery can be a promising approach to increase bioavailability, minimize drug loss by degradation and prevent harmful side effects by increasing specific cell targeting.

Since the outbreak of coronavirus disease 2019 (COVID-19) in 2019, it is gaining worldwide attention at the moment. Apart from respiratory manifestations, neurological dysfunction in COVID-19 patients, especially the occurrence of cerebrovascular diseases (CVD), has been intensively investigated. In this review, the effects of COVID-19 infection on CVD were summarized as follows: (I) angiotensin-converting enzyme 2 (ACE2) may be involved in the attack on vascular endothelial cells by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to endothelial damage and increased subintimal inflammation, which are followed by hemorrhage or thrombosis; (II) SARS-CoV-2 could alter the expression/activity of ACE2, consequently resulting in the disruption of renin-angiotensin system which is associated with the occurrence and progression of atherosclerosis; (III) upregulation of neutrophil extracellular traps has been detected in COVID-19 patients, which is closely associated with immunothrombosis; (IV) the inflammatory cascade induced by SARS-CoV-2 often leads to hypercoagulability and promotes the formation and progress of atherosclerosis; (V) antiphospholipid antibodies are also detected in plasma of some severe cases, which aggravate the thrombosis through the formation of immune complexes; (VI) hyperglycemia in COVID-19 patients may trigger CVD by increasing oxidative stress and blood viscosity; (VII) the COVID-19 outbreak is a global emergency and causes psychological stress, which could be a potential risk factor of CVD as coagulation, and fibrinolysis may be affected. In this review, we aimed to further our understanding of CVD-associated COVID-19 infection, which could improve the therapeutic outcomes of patients. Personalized treatments should be offered to COVID-19 patients at greater risk for stroke in future clinical practice.

Aims Patients with advanced heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) and concurrent coronavirus disease 2019 (COVID‐19) might have a higher risk of severe events. Methods and results We retrospectively studied 16 patients with advanced HFrEF who developed COVID‐19 between 1 March and 29 May 2020. Follow‐up lasted until 30 September. Ten patients previously hospitalized with decompensated HFrEF were infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) during hospitalization. Six patients undergoing ambulatory care at initiation of COVID‐19 symptoms were hospitalized because of advanced HFrEF. All patients who experienced worsening of HFrEF due to COVID‐19 required higher doses or introduction of additional inotropic drugs or intra‐aortic balloon pump in the intensive care unit. The mean intravenous dobutamine dose before SARS‐CoV‐2 infection in previously hospitalized patients (n = 10) and the median (inter‐quartile range) peak intravenous dobutamine dose during SARS‐CoV‐2 infection in all patients (n = 16) were 2 (0–7) μg/kg/min and 20 (14–20) (P

Panax japonicus, which in the Tujia dialect is known as “Baisan Qi” and “Zhujieshen”, is a classic “qi” drug of Tujia ethnomedicine and it has unique effects on disease caused by “qi” stagnation and blood stasis. This paper serves as the basis of further scientific research and development of Panax japonicus. The pharmacology effects of molecular pharmacology were discussed and summarized. P. japonicus plays an important role on several diseases, such as rheumatic arthritis, cancer, cardiovascular agents, and this review provides new insights into P. japonicus as promising agents to substitute ginseng and notoginseng.

Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population.Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan.Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10).Conclusions: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

Human malignancies are one of the major health-related issues though out the world and anticipated to rise in the future. The development of novel drugs/agents requires a huge amount of cost and time that represents a major challenge for drug discovery. In the last three decades, the number of FDA approved drugs has dropped down and this led to increasing interest in drug reposition or repurposing. The present review focuses on recent concepts and therapeutic opportunities for the utilization of antidiabetics, antibiotics, antifungal, anti-inflammatory, antipsychotic, PDE inhibitors and estrogen receptor antagonist, Antabuse, antiparasitic and cardiovascular agents/drugs as an alternative approach against human malignancies. The repurposing of approved non-cancerous drugs is an effective strategy to develop new therapeutic options for the treatment of cancer patients at an affordable cost in clinics. In the current scenario, most of the countries throughout the globe are unable to meet the medical needs of cancer patients because of the high cost of the available cancerous drugs. Some of these drugs displayed potential anti-cancer activity in preclinic and clinical studies by regulating several key molecular mechanisms and oncogenic pathways in human malignancies. The emerging pieces of evidence indicate that repurposing of drugs is crucial to the faster and cheaper discovery of anti-cancerous drugs.

Background: In December 2019, pneumonia associated with COVID-19 has spread from Wuhan to other areas in China. In the present study, we aimed to further clarify the clinical features and outcomes of acute kidney injury (AKI) in patients infected with COVID-19 in Xiangyang, Hubei, China. Methods: All confirmed cases of COVID-19 with AKI in Xiangyang Central Hospital from January 22 to May 31, 2020, were included in this retrospective study. Data of epidemiological, clinical, laboratory, radiological tests, treatment, complication, and outcomes were collected and analyzed. Patients were divided into intensive care unit (ICU) group and isolation ward (non-ICU) group. Results: Of the total patients, 33.3% in the non-ICU group and 85.7% in the ICU group had chronic diseases. In addition, 85.7% of patients in the ICU group died. The most common symptoms were fever, cough, and fatigue. The lymphocyte count in the ICU group was significantly reduced compared with the non-ICU group. The chest computed tomography (CT) images appeared showed multiple mottles and ground-glass opacity. Strip shadow could be found in chest CT images of some recovered patients. All patients received antiviral treatment. Most patients in the ICU group were given methylprednisolone, immunoglobulin, antibiotics, and mechanical ventilation and 35.7% of patients in the ICU group received continuous renal replacement therapy. Conclusions: Elderly with chronic comorbidities were more susceptible to COVID-19, showing a higher mortality rate due to multiple organ damage, and 35.7% of patients with AKI in ICU received renal replacement therapy. Moreover, part of the cured patients might need additional time to recover for poor lung function.

Aryloxyphenylpiperazinylpropanols are a group of compounds exhibiting a wide range of biological activities, affecting the central nervous system and many cardiovascular mechanisms among them. As cardiovascular agents, aryloxyphenylpiperazinylpropanols work as antihypertensives, antiarrhythmics, cardiotonics or antiaggregants. The mechanism of action is almost always an α1-adrenolytic or combined α1- and β-adrenolytic effect, but sometimes other mechanisms (e.g., Ca2+ antagonism or phosphodiesterase inhibition) antagonism or phosphodiesterase inhibition) can positively participate. In some cases, compounds with a small modification of the connecting chain also exhibit the desired cardiovascular effects. Several studies dealt with chirality of aryloxyphenylpiperazinylpropanols and determined the differences between the particular activities of racemic and enantiomeric compounds.

The study aimed to investigate whether specific medications used in the treatment chronic diseases affected either the development and/ or severity of COVID-19 in a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zheijang, China. Using a cohort of 578 COVID-19 cases and 48,667 population-based controls from Zheijang, China we tested the role of usage of cardiovascular, antidiabetic and other medications on risk and severity of COVID 19. Analyses were adjusted for age, sex and BMI and for presence of relevant comorbidities. Individuals with hypertension taking calcium channel blockers had significantly increased risk [odds ratio (OR)= 1.73 (95% CI 1.2-2.3)] of manifesting symptoms of COVID-19 whereas those taking angiotensin receptor blockers and diuretics had significantly lower disease risk (OR=0.22; 95%CI 0.15-0.30 and OR=0.30; 95%CI 0.19-0.58 respectively). Among those with type 2 diabetes, dipeptidyl peptidase-4 inhibitors (OR= 6.02; 95% CI 2.3-15.5) and insulin (OR= 2.71; 95% CI 1.6-5.5) were more and glucosidase inhibitors were less prevalent (OR= 0.11; 95% CI 0.1-0.3) among with COVID-19 patients.Drugs used in the treatment of hypertension and diabetes influence the risk of development of COVID-19, but, not its severity.Study highlightsWhat is the current knowledge on the topic?Cardiovascular disease and Diabetes have been highlighted as comorbidities contributing to a more severe form of COVID-19 and medication to treat them may also influence the risk of COVID-19 and its clinical outcomes.What question did this study address?Does specific medications used in the treatment of chronic diseases influence the risk for the susceptibility to SARS CoV-2 infection of severity of COVID-19?What does this study add to our knowledge?The study confirms that higher BMI, diabetes and cardio/ cerebrovascular disease as independent risk factors for the development of COVID-19. Angtiotensin Receptor Blockers (ARBs) and diuretics were associated with reduced risk and Calcium Channel Blockers (CCBs) with increased risk of developing COVID-19. Among those with type 2 diabetes, dipeptidyl peptidase-4 and were associated with increased and glucosidase inhibitors with reduced risk development of COVID-19. None of the antihypertensive or anti-diabetic drugs were associated with increased risk of severe or critical form of the infection.Drugs used in the treatment of hypertension and diabetes influence the risk of development of COVID-19, but are not associated with severity of the disease.How might this change clinical pharmacology or translational science?Findings from the current large case-control study confirmed no evidence to alter ARBs or ACEIs therapy in the context of COVID-19 severity in clinical practice. Hypertension significantly increases the risk of severe or critical SARS-CoV-2 infection indicating that carefully controlled blood pressure should be a priority to reduce the healthcare burden of COVID-19.

Objective To describe demographic, clinical, and lung base CT findings in COVID-19 patients presenting with abdominal complaints. Methods In this retrospective study, 76 COVID-19 patients who underwent abdominal CT for abdominal complaints from March 1 to April 15, 2020, in a large urban multihospital Health System were included. Those with positive abdominal CT findings (n = 14) were then excluded, with 62 patients undergoing final analysis (30M/32F; median age 63 years, interquartile range (IQR) 52–75 years, range 30–90 years). Demographic and clinical data were extracted. CT lung base assessment was performed by a cardiothoracic radiologist. Data were compared between discharged and hospitalised patients using Wilcoxon or Fisher’s exact tests. Results The majority of the population was non-elderly (56.4%, < 65 years) and most (81%) had underlying health conditions. Nineteen percent were discharged and 81% were hospitalised. The most frequent abdominal symptoms were pain (83.9%) and nausea/vomiting/anorexia (46.8%). Lung base CT findings included ground-glass opacities (95.2%) in a multifocal (95.2%) and peripheral (66.1%) distribution. Elevated laboratory values (when available) included C-reactive protein (CRP) (97.3%), D-dimer (79.4%), and ferritin (68.8% of males and 81.8% of females). Older age (p = 0.045), hypertension (p = 0.019), and lower haemoglobin in women (p = 0.042) were more frequent in hospitalised patients. There was no difference in lung base CT findings between discharged and hospitalised patients (p > 0.165). Conclusions COVID-19 patients can present with abdominal symptoms, especially in non-elderly patients with underlying health conditions. Lung base findings on abdominal CT are consistent with published reports. Radiologists should be aware of atypical presentations of COVID-19. Key Points • COVID-19 infected patients can present with acute abdominal symptoms, especially in non-elderly patients with underlying health conditions, and may frequently require hospitalisation (81%). • There was no difference in lung base CT findings between patients who were discharged and those who were hospitalised. • Lung base CT findings included multifocal and peripheral ground-glass opacities, consistent with published reports.

The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The link between cardiovascular disease and COVID-19 appears to be twofold. First, some reports of data indicate that certain groups of patients are more at risk of COVID-19. This includes patients with cardiovascular risk factors or pre-existing cardiovascular conditions and older patients. In addition, these patients incur disproportionately worse outcome. Second, SARS-CoV2 infection can be complicated by life-threatening cardiovascular acute diseases. Despite the rapid evolution of data on this pandemic, this review aims to highlight the cardiovascular considerations related to COVID-19 whether as comorbidities including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2 or related to acute cardiovascular complications.

Aims: Homozygosity for a 4-missense single-nucleotide-polymorphism-haplotype of the human BPIFB4 gene is enriched in long-living individuals. Delivery of this Longevity Associated Variant (LAV) improved revascularisation and reduced endothelial dysfunction and atherosclerosis in mice through a mechanism involving the stromal cell-derived factor-1 (SDF-1). Here, we investigated if delivery of the LAV-BPIFB4 gene may attenuate the progression of diabetic cardiomyopathy. Methods and Results: Compared with age-matched lean controls, diabetic db/db mice showed altered echocardiographic indices of diastolic and systolic function and histological evidence of microvascular rarefaction, lipid accumulation, and fibrosis in the myocardium. All these alterations, as well as endothelial dysfunction, were prevented by systemic LAV-BPIFB4 gene therapy using an adeno-associated viral vector serotype 9 (AAV9). In contrast, AAV9-wild type (WT)-BPIFB4 exerted no benefit. Interestingly, the LAV-BPIFB4-treated mice showed increased SDF-1 levels in peripheral blood and myocardium and upregulation of cardiac myosin heavy chain isoform alpha, a contractile protein that was reduced in diabetic hearts. SDF-1 upregulation was instrumental to LAV-BPIFB4-induced benefit as both haemodynamic and structural improvements were inhibited by an orally active antagonist of the SDF-1 CXCR4 receptor. Conclusions: In mice with type-2 diabetes, LAV-BPIFB4 gene therapy promotes an advantageous remodelling of the heart, allowing it to better withstand diabetes-induced stress. These results support the viability of transferring healthy characteristics of longevity to attenuate diabetic cardiac disease.

Drug induced liver injury (DILI) may be different in the East compared to the West due to differing disease prevalence, prescribing patterns and pharmacogenetic profiles. To review existing literature on causative agents of DILI in the East compared to the West, a comprehensive literature search was performed on electronic databases: MEDLINE/PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure without language restrictions. Studies which involve patients having DILI and reported the frequency of causative agents were included. A random effects model was applied to synthesize the current evidence using prevalence of class-specific and agent-specific causative drugs with 95% confidence intervals. Of 6,914 articles found, 12 showed the distribution of drugs implicated in DILI in the East with a total of 33,294 patients and 16 in the West with a total of 26,069 DILI cases. In the East, the most common agents by class were anti-tuberculosis drugs (26.6%), herbal and alternative medications (25.3%), and antibiotics (15.7%), while in the West, antibiotics (34.9%), cardiovascular agents (17.3%), and non-steroidal anti-inflammatory drugs (12.5%) were the commonest. For individual agents, the most common agents in the East were isoniazid-rifampicin-pyrazinamide (25.4%), phenytoin (3.5%), and cephalosporin (2.9%) while in the West, amoxicillin-potassium clavulanate combination acid (11.3%), nimesulide (6.3%), and ibuprofen (6.1%) were the commonest. There was significant heterogeneity due to variability in single-centre compared to multi-centre studies. Differences in DILI in the East versus the West both in drug classes and individual agents are important for clinicians to recognize. (Clin Mol Hepatol 2020;26:142-154)

Background: Beta-blockers are one of the most important classes of cardiovascular agents and have been considered a cornerstone therapy in heart diseases, such as heart failure (HF) and atrial fibrillation (AF). Among different beta-blockers, metoprolol is a selective beta(1)-adrenergic antagonist, which has been extensively used since the 1970s. Areas of Uncertainty: Although current guidelines include recommendations for the use of controlled-release metoprolol succinate in specific HF and AF indications, and despite extensive clinical experience with metoprolol, comparative evidence on the use of metoprolol succinate compared with other beta-blockers in these indications is limited. Data Sources: We systematically reviewed the data from head-to-head studies directly comparing this compound with other beta-blockers in the treatment of HF or AF. Only clinical trials and observational studies were considered; no other limits were applied. The quality and relevance of retrieved articles were reviewed. Results: A total of 18 articles of the 353 articles identified were selected for inclusion; 12 HF articles and 6 for AF. Additional references were identified from the bibliographies of retrieved articles. The studies show that oral prophylaxis with an appropriate dose of metoprolol may reduce new incidents of AF in high-risk patients. Furthermore, metoprolol succinate is associated with significant mortality and morbidity benefits in the treatment of HF. Conclusions: Despite the introduction of newer beta-blockers with differing clinical characteristics since its introduction, metoprolol succinate remains a useful drug in both HF and AF.

Introduction 2.5 million people in the UK are aged over 80 and up to 50% can be considered frail. Complex co-morbidities and polypharmacy are linked with adverse drug effects and negative outcomes. NICE recommends a medication review yearly, and a hospital admission provides an opportunity for this. STOPP-Frail is a screening tool designed to highlight medications that could be reduced/stopped with a view to improving quality of life. We conducted a quality improvement project to quantify levels of inappropriate prescribing at Croydon University Hospital (CUH), with a view to de-prescribing and reducing adverse drug effects. Methods A retrospective analysis was carried out on the Elderly Care wards at CUH. Data was collected from 60 consecutive patients discharged from 1st November 2018, utilising electronic Cerner records. Recorded medication on admission and discharge, noting any amendments in accordance with the STOPP-Frail criteria. Results Data collected from 60 patients; one exclusion for not meeting STOPP-Frail criteria (n=59). Median age 86 years (69 to 103 years). Mean number of medications on admission 7.42 (1 to 15). 93.2% patients had polypharmacy (defined as ≥ 4 medications). Mean number of medications on discharge 8.22; an increase of 0.8/patient. 19.4% admission medications met STOPP-Frail criteria for inappropriate prescriptions. Only 18.8% of these were reduced or stopped during admission. Gastrointestinal and cardiovascular medications were most commonly inappropriately prescribed (n=27 and 24 respectively). Most common medications not amended were lipid-lowering therapies (n=21) and proton-pump inhibitors (n= 20). Conclusions The opportunity to rationalise medication in the frailest patients admitted to CUH is missed in over 80% of cases. STOPP-Frail provides clear guidance to aid clinicians in reducing inappropriate prescribing. An educational programme is in place to highlight medication rationalisation and guide clinicians in the use of the STOPP-Frail tool. This includes doctors’ induction, departmental teaching, posters and computer flash cards.

Background The ULISSE registry evaluated the real-world performance of the Ultimaster® biodegradable polymer sirolimus-eluting stent (BP-SES) in a multicenter-independent cohort of patients undergoing percutaneous coronary intervention, including a large proportion of diabetes mellitus (DM) patients. Methods In this subgroup analysis, 1,660 consecutive patients, 2,422 lesions, treated with BP-SES enrolled in the ULISSE registry were divided in two groups: DM (485 patients, 728 lesions) and non-DM (1,175 patients, 1,694 lesions). Primary endpoint was target lesion failure (TLF), a composite endpoint of cardiac-death, target-vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR) at 1-year. Secondary endpoint was TLR at 1-year. Results At 1-year follow-up TLF occurred in 5% overall patients and was significantly higher in DM patients (8 vs. 3.7%; p = .001), due to more cardiac deaths (3.4 vs. 1.1%; p = .002). TLR occurred in 3.2% overall patients, and it was not significantly higher in DM compared to non-DM patients (4.4 vs. 2.8%; p = .114). The incidence of stent thrombosis was low and similar between groups (0.4 vs. 0.9%; p = .526). Insulin-treated DM (ITDM) patients showed higher rate of TLF as compared to non-ITDM patients (13 vs. 6.5%; p = .041), but similar rate of TLR (6 vs. 4%; p = .405). After adjustment for relevant comorbidities, DM was not significantly associated with TLF or cardiac death in patients undergoing BP-SES implantation. Conclusions This study is the first all-comers evaluation of BP-SES in DM patients. Our findings show that DM patients, mostly those with ITDM, still represent a vulnerable population and experience significantly higher rate of TLF. Overall BP-SES efficacy is considerable, although not statistically significant higher rate of TLR is still present in DM compared to non-DM patients.

Background: Mobile health technology offers promising means to implement public health strategies for the prevention and management of chronic conditions. However, at the moment, there is a dearth of both; specific mobile health tools tailored for the knowledge and language needs of Indian population; as well as enough systematic and scientific clinical data to analyse their impact in varied Indian socioeconomic and disease populations. Objective: To develop a smartphone-based bilingual educational mobile application for heart patients and pilot test in an Indian clinical setting. Methods: An Android™ based mobile application was developed according to a systematic instructional design model. Thereafter, expert assessment was done by 3 software engineers and 2 healthcare professionals using a peer-reviewed, objective and multidimensional Mobile Application Rating Scale (MARS). A pilot user satisfaction evaluation was done based on feedback from 35 Coronary Artery Disease patients visiting Cardiology outpatient Department of a North Indian tertiary care centre. Results: An Android™ based mobile application named as ‘Happy Heart’ was developed. The content was developed in both Hindi and English under professional supervision. For this mobile application, the Mean MARS score was 3.60 ± 0.86 and subjectivity score was 3.30 ± 1.03. The overall user satisfaction response for the mobile application was 4.09 ± 0.75 indicating that most of the testers found it useful. Conclusion: This mobile application is developed as a research tool to further conduct a clinical study in Coronary Artery Disease Patients. Current evaluation was a pilot testing wherein this application showed promising results.

We aimed to determine the association of vasoactive-inotropic score (VIS) and vasoactive-ventilation-renal (VVR) score with in-hospital mortality and functional outcomes at discharge of children who receive ECMO. A sub-analysis of the multicenter, prospectively collected data by the Collaborative Pediatric Critical Care Research Network (CPCCRN) for Bleeding and Thrombosis on ECMO (BATE database) was conducted. Of the 514 patients who received ECMO across eight centers from December 2012 to February 2016, 421 were included in the analysis. Patients > 18 years of age, patients placed on ECMO directly from cardiopulmonary bypass or as an exit procedure, or patients with an invalid or missing VIS score were excluded. Higher VIS (OR = 1.008, 95% CI: 1.002–1.014, p = 0.011) and VVR (OR: 1.006, 95% CI: 1.001–1.012, p = 0.023) were associated with increased mortality. VIS was associated with worse Pediatric Cerebral Performance Category (PCPC) (OR = 1.027, 95% CI: 1.010–1.044, p = 0.002) and Pediatric Overall Performance Category (POPC) score (OR = 1.023, 95% CI: 1.009–1.038, p = 0.002) at discharge. No association was found between VIS or VVR and Functional Status Score (FSS) at discharge. Using multivariable analyses, controlling for ECMO mode, ECMO location, ECMO indication, primary diagnosis, and chronic diagnosis, extremely high VIS and VVR were still associated with increased mortality.

IntroductionObesity is a common disease and a known risk factor for many other conditions such as hypertension, type 2 diabetes, and cancer. Treatment options for obesity include lifestyle changes, pharmacotherapy, and surgical interventions such as bariatric surgery. In this study, we examine the use of prescription drugs and dietary supplements by the individuals with obesity.MethodsWe conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) data 2003-2014. We used multivariate logistic regression to analyze the correlations of demographics and obesity status with the use of prescription drugs and dietary supplement use. We also built machine learning models to classify prescription drug and dietary supplement use using demographic data and obesity status.ResultsIndividuals with obesity are more likely to take cardiovascular agents (OR=1.265, 95% CI 1.222-1.311) and metabolic agents (OR=1.398, 95% CI 1.343-1.456) than individuals without obesity. The best performing model for classifying prescription drug use had the accuracy of 74.5% and the AUROC of 0.817.ConclusionsThis study can inform clinical practice and patient education of the use of prescription drugs and dietary supplements and their correlation with obesity.

Nowadays, nitrogenous heterocyclic molecules have attracted a great deal of interest among medicinal chemists. Among these potential heterocyclic drugs, benzimidazole scaffolds are considerably prevalent. Due to their isostructural pharmacophore of naturally occurring active biomolecules, benzimidazole derivatives have significant importance as chemotherapeutic agents in diverse clinical conditions. Researchers have synthesized plenty of benzimidazole derivatives in the last decades, amidst a large share of these compounds exerted excellent bioactivity against many ailments with outstanding bioavailability, safety, and stability profiles. In this comprehensive review, we have summarized the bioactivity of the benzimidazole derivatives reported in recent literature (2012–2021) with their available structure-activity relationship. Compounds bearing benzimidazole nucleus possess broad-spectrum pharmacological properties ranging from common antibacterial effects to the world’s most virulent diseases. Several promising therapeutic candidates are undergoing human trials, and some of these are going to be approved for clinical use. However, notable challenges, such as drug resistance, costly and tedious synthetic methods, little structural information of receptors, lack of advanced software, and so on, are still viable to be overcome for further research.

Purpose: This study examined medication use by individuals with tinnitus who were seeking help for their tinnitus by means of a psychological intervention. Method: This study used a cross-sectional survey design and included individuals with tinnitus enrolled in an Internet-based cognitive behavioral therapy trial ( n = 439). Study participants provided demographic details, completed various structured questionnaires and provided details about the medications used. The self-reported medications were classified using the United States Pharmacopeial Medicare Model Guidelines v7.0. Results: Current medication use was reported by 67% ( n = 293) of the study participants. Those currently using medication were older; had consulted their primary care physician, had greater tinnitus severity, depression, anxiety, and insomnia when compared with those not reporting any current medication use. The top 10 medication used included cardiovascular agents ( n = 162; 55.3%), antidepressants ( n = 80; 27.3%), electrolytes/minerals/metals/vitamins ( n = 70; 23.9%), respiratory tract/pulmonary agents ( n = 62; 21.2%), anxiolytics ( n = 59; 20.1%), hormonal agents/stimulant/replacement/modifying (thyroid; n = 45; 15.4%), gastrointestinal agents ( n = 43; 14.7%), analgesics ( n = 33; 11.3%), blood glucose regulators ( n = 32; 10.9%), and anticonvulsants ( n = 26; 8.87%). Some associations between type of medication used and demographic or tinnitus-related variables were noted especially for the cardiovascular agents, electrolytes/minerals/metals/vitamins, and anxiolytics. Conclusions: This exploratory study indicated a large percentage of patients using medication and a range of medications. Further studies are required to assess the effects of such medications on the tinnitus percept and concurrent medication moderate treatment effects.

We assessed the feasibility and the procedural and long-term safety of intracoronary (i.c) imaging for documentary purposes with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary PCI in the setting of IBIS-4 study. IBIS4 (NCT00962416) is a prospective cohort study conducted at five European centers including 103 STEMI patients who underwent serial three-vessel coronary imaging during primary PCI and at 13 months. The feasibility parameter was successful imaging, defined as the number of pullbacks suitable for analysis. Safety parameters included the frequency of peri-procedural complications, and major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction (MI) and any clinically-indicated revascularization at 2 years. Clinical outcomes were compared with the results from a cohort of 485 STEMI patients undergoing primary PCI without additional imaging. Imaging of the infarct-related artery at baseline (and follow-up) was successful in 92.2 % (96.6 %) of patients using OCT and in 93.2 % (95.5 %) using IVUS. Imaging of the non-infarct-related vessels was successful in 88.7 % (95.6 %) using OCT and in 90.5 % (93.3 %) using IVUS. Periprocedural complications occurred < 2.0 % of OCT and none during IVUS. There were no differences throughout 2 years between the imaging and control group in terms of MACE (16.7 vs. 13.3 %, adjusted HR1.40, 95 % CI 0.77-2.52, p = 0.27). Multi-modality three-vessel i.c. imaging in STEMI patients undergoing primary PCI is consistent a high degree of success and can be performed safely without impact on cardiovascular events at long-term follow-up.

Background There is limited research on hypertrophic cardiomyopathy (HCM), which is the most common inherited cardiac disorder, in diverse populations, including Black individuals. Current literature lacks comprehensive data on HCM disease expression, comorbidities, and outcomes in this historically disadvantaged group. The purpose of this study was to examine structural HCM characteristics, comorbidities, and outcomes in a Black and White cohort with HCM. Methods and Results The study was a subgroup analysis from a longitudinal, prospective study on HCM, with supplemental chart review. The sample included adults (≥18 years) with a clinical diagnosis of HCM, who self‐identified as Black/African American or White. The study sample comprised 434 individuals; 57 (13.1%) were Black, and 180 (41.5%) were women. Black patients were younger than White patients, 54.6 (13.4) versus 62.5 (14.8) years, P=0.001. Black patients were more likely to have sub‐basal and diffuse hypertrophy, 22 (38.6%) versus 56 (14.9%), P

Aim The aim of this study was to examine the development of drug purchases over the course of the coronavirus crisis in Germany in 2020. Materials and methods The evaluations in this retrospective cross-sectional study are based on the IMS RPM (Regional Pharmaceutical Market) weekly database, which shows weekly purchases by public pharmacies from full-service wholesalers at the time the pharmacy purchase is made in Germany. The outcome of this investigation was the development of cardiovascular drug sales by packing unit over all 52 weeks of 2020. Results We found an increase of 68% in week 12 compared to the average sales for weeks 2 - 11, 2020 (vs. -2% in week 12, 2019), while the increase in week 51 was 61%, compared to the average sales for weeks 13 - 50, 2020 (vs. 35% in week 51, 2019). The largest increases in week 12 were for calcium channel blockers (64%), and the largest increases in week 51 were for lipid-lowering drugs (67%). Conclusion The results of this retrospective cross-sectional study suggest that the COVID-19 lockdown in Germany was associated with a significant surge in pharmacy purchases of cardiovascular drugs, indicating panic buying. Although there were no drug shortages during the first lockdown, this panic buying recurred shortly before the second lockdown, albeit to a lesser extent.

Management of constrictive pericarditis is often clinically challenging. Heart rate (HR) modulation using ivabradine is associated with improved clinical outcomes in patients with systolic heart failure, although it remains uninvestigated for other clinical purposes. We aimed to assess the impact of HR control in patients with constrictive pericarditis. In this retrospective study, consecutive patients who were diagnosed with constrictive pericarditis were included. Transthoracic echocardiography was performed at index discharge (day 0). The impact of HR difference between actual HR and ideal HR, which was calculated using a formula consisting of deceleration time, on heart failure readmission rates was investigated. A total of 15 patients (73 years old on median, 11 men) with constrictive pericarditis were included. On median, actual HR was 71 bpm and ideal HR was 81 bpm. Heart failure readmission rates were stratified into three groups by the HR difference: (1) optimal HR group satisfying "-10 bpm ≤ HR difference ≤ 10 bpm" (n = 4, 0.067 events per year); (2) lower HR group satisfying "HR difference-10 bpm" (n = 7, 0.118 events per year, incidence rate ratio 1.98, 95% confidence interval 0.06-61.6); (3) higher HR group satisfying "HR difference10 bpm" (n = 4, 0.231 events per year, incidence rate ratio 9.22, 95% confidence interval 0.36-237.8). In conclusion, non-optimized HR was associated with an increased risk of heart failure recurrence in patients with constrictive pericarditis. Prospective assessment of deceleration time-guided HR optimization in patients with constrictive pericarditis is needed.

The endothelium, a cellular monolayer lining the blood vessel wall, plays a critical role in maintaining multiorgan health and homeostasis. Endothelial functions in health include dynamic maintenance of vascular tone, angiogenesis, hemostasis, and the provision of an antioxidant, anti-inflammatory, and antithrombotic interface. Dysfunction of the vascular endothelium presents with impaired endothelium-dependent vasodilation, heightened oxidative stress, chronic inflammation, leukocyte adhesion and hyperpermeability, and endothelial cell senescence. Recent studies have implicated altered endothelial cell metabolism and endothelial-to-mesenchymal transition as new features of endothelial dysfunction. Endothelial dysfunction is regarded as a hallmark of many diverse human panvascular diseases, including atherosclerosis, hypertension, and diabetes. Endothelial dysfunction has also been implicated in severe coronavirus disease 2019. Many clinically used pharmacotherapies, ranging from traditional lipid-lowering drugs, antihypertensive drugs, and antidiabetic drugs to proprotein convertase subtilisin/kexin type 9 inhibitors and interleukin 1β monoclonal antibodies, counter endothelial dysfunction as part of their clinical benefits. The regulation of endothelial dysfunction by noncoding RNAs has provided novel insights into these newly described regulators of endothelial dysfunction, thus yielding potential new therapeutic approaches. Altogether, a better understanding of the versatile (dys)functions of endothelial cells will not only deepen our comprehension of human diseases but also accelerate effective therapeutic drug discovery. In this review, we provide a timely overview of the multiple layers of endothelial function, describe the consequences and mechanisms of endothelial dysfunction, and identify pathways to effective targeted therapies. SIGNIFICANCE STATEMENT: The endothelium was initially considered to be a semipermeable biomechanical barrier and gatekeeper of vascular health. In recent decades, a deepened understanding of the biological functions of the endothelium has led to its recognition as a ubiquitous tissue regulating vascular tone, cell behavior, innate immunity, cell-cell interactions, and cell metabolism in the vessel wall. Endothelial dysfunction is the hallmark of cardiovascular, metabolic, and emerging infectious diseases. Pharmacotherapies targeting endothelial dysfunction have potential for treatment of cardiovascular and many other diseases.

Purpose To identify randomized controlled trials that compared antiplatelet monotherapy to combination antiplatelet plus anticoagulant therapy and evaluated major adverse cardiovascular events (MACE) or major adverse limb events (MALE), death, or bleeding in patients with lower extremity peripheral artery disease (PAD). Summary A systematic search of MEDLINE, Embase, and CENTRAL databases revealed 5 trials. Two trials consisted of patients with stable PAD, while 3 trials examined patients with PAD post revascularization. Antiplatelet therapy was mostly aspirin (81-325 mg daily), and anticoagulation included rivaroxaban 2.5 mg twice daily or warfarin. Duration of follow-up ranged from 12 to 38 months. Two trials had low risk of bias, whereas 3 trials had high/unclear risk of bias. For patients with stable PAD, one trial showed that use of warfarin (or acenocoumarol) with antiplatelet therapy did not reduce MACE, MALE, or cardiovascular or all-cause death but increased the risk of life-threatening bleeding. A second trial demonstrated that low-dose rivaroxaban plus antiplatelet therapy lowered the risk of MACE and MALE, with no effect in preventing cardiovascular or all-cause death, but increased the risk of major bleeding. For patients with PAD post revascularization receiving warfarin and antiplatelet therapy, 2 trials showed no benefit in MACE or MALE but increased or similar rates of all-cause death and major bleeding. In a third trial, low-dose rivaroxaban plus aspirin reduced occurrence of the composite of MACE and MALE but increased major bleeding, with no effect on cardiovascular or all-cause death. Conclusion Dual-pathway inhibition with low-dose rivaroxaban and aspirin reduced MACE and MALE in patients with stable or revascularized PAD, but net clinical benefit is questionable.

Postural orthostatic tachycardia syndrome (POTS) is estimated to impact millions of people each year. However, there is no established gold standard for its treatment. Bupropion is a norepinephrine and a dopamine reuptake inhibitor and has been implicated as a potential treatment for POTS. We performed a non-randomized retrospective chart review on 47 patients with POTS with statistical analysis evaluating for significant findings including reduced orthostasis and improvement of symptoms with the use of bupropion. Bupropion was not associated with a statistically significant improvement in orthostatic vitals but there was an overall reduction in reported syncope. While the use of bupropion does not show a statistically significant impact on orthostatic vitals in patients with POTS, it did show a degree of improvement in syncope and as such might be useful in patients with syncope-predominant POTS.

Hyperthermia occurs when heat accumulation surpasses the body’s ability for heat dissipation. Many drugs may affect thermoregulation. This narrative review aimed to provide an overview of the current literature concerning reports of drug-associated non-pyrogenic hyperthermia. A comprehensive search was performed across 5 databases covering the period of inception to March 2019, for publications that reported hyperthermia associated with drug use. Studies that reported potential drug association with hyperthermia due to altered thermoregulatory mechanisms were included. Case reports of less than 3 cases were excluded, as well as hyperthermia due to other causes, such as hypersensitivity, malignant hyperthermia and neuroleptic malignant syndrome. The primary outcomes of interest were hospitalisation and mortality. The literature search initially identified a total of 2609 records. Based on full-text analysis, 11 articles met the inclusion criteria, of which there were 5 case-control studies, 2 case series and 4 retrospective analyses. Studies reported heat-related hospitalisations or emergency department presentations associated with the use of psychotropics (antipsychotics, antidepressants and anxiolytics), anticholinergics, antihistamines, diuretics, cardiovascular agents, non-steroidal anti-inflammatory drugs and anticoagulants. Psychotropic drugs were reported to be associated with increased heat-related mortality, other than through neuroleptic malignant syndrome, but findings varied among the studies. Given the relative lack of publications, more research is necessary to study specific effects of drugs on body temperature and the likelihood of inducing non-pyrogenic hyperthermia. In particular, psychotropics, anticholinergics, diuretics and cardiovascular agents are of interest for future studies.

Introduction This study aimed to identify drug utilization patterns in patients initiating sodium glucose co-transporter-2 inhibitors (SGLT2i) in the first 3 years of their launch in Japan. Methods This was a retrospective study using three administrative databases in Japan: a pharmacy claims database, a hospital-based database, and an insurance claims database. Prescription data were extracted from adult outpatients with diabetes who started SGLT2i between April 2014 and March 2017 to evaluate pre-index and concomitant medications. For glimepiride and insulin co-users, dose at SGLT2i add-on was also assessed. Results Data from a total of 14,861 patients in the pharmacy dataset (P-dataset), 27,039 in the hospital dataset (H-dataset), and 12,408 in the insurance dataset (I-dataset) were analyzed. The majority of SGLT2i new users (ca. 70%) were taking one to three concomitant antidiabetic medications. Around half of SGLT2i initiators used dipeptidyl peptidase 4 inhibitors and/or biguanides before using SGLT2i or concomitantly with SGLT2i. The average daily glimepiride dose decreased from 2.1 mg/day during the pre-index period to 1.8 mg/day at SGLT2i add-on in the P-dataset and from 1.9 to 1.7 mg/day in the both H- and I-datasets, respectively, with a decreasing trend observed during the first 3 years of launch. The average daily insulin dose at SGLT2i add-on was higher during the first 15 months of launch and then decreased thereafter. Nearly 40% or more SGLT2i new users were taking at least five concomitant medications: cardiovascular agents were predominantly co-prescribed. Conclusion SGLT2i were frequently used as second- or later-line treatment and as part of a dual, triple, or quadruple regimen, as well as co-prescribed with many other medications in the first 3 years of their launch. For SGLT2i users taking concomitant SU or insulin medications, the average daily doses of SU and insulin at SGLT2i add-on decreased slightly over the study period. Funding Astellas Pharma Inc., Tokyo, Japan. Electronic Supplementary Material The online version of this article (10.1007/s13300-019-00710-2) contains supplementary material, which is available to authorized users.

Purpose: Maternal cardiac disease is one of the major causes of non-obstetric maternal morbidity and mortality. In the treatment of cardiovascular diseases during pregnancy, it is important to prescribe the drugs that control maternal disease and to minimize potential drug-related risk to the fetus. The aim of this study is to evaluate the teratogenic safety of cardiovascular drugs in pregnancy.Materials and Methods: We collected data of pregnant women who used drugs for cardiovascular disorders and admitted to our unit for drug analysis between 2014 and 2018. Teratology Information Service assessed the teratogenic risk of drugs. After delivery, a follow-up was conducted with families to obtain the presence of any congenital malformations or adverse neurodevelopmental effects in the infant. Results: Use of ramipril in the first six weeks of pregnancy resulted in spontaneous abortus at the 10th week. Use of warfarin in the first 12 weeks resulted in exitus at the postnatal fourth day. Telmisartan exposure in the first six weeks resulted in intrauterine death in the 18th gestational week.Conclusion: Drugs acting on renin-angiotensin system should be discontinued when pregnancy is detected. Warfarin is contraindicated for use in pregnancy except mechanical heart valve pregnancies with high risk of thromboembolism, as it leads to coumarin embryopathy and nervous system anomalies in the first trimester exposures. Pregnant women should be directed to the teratogenic drug analysis and evaluated for possible increase in drug-related congenital malformation risks at early gestational period. Teratogenic risk counselling and follow-up ensures reliable data on drug safety during pregnancy.

Nickel foam (NF) was used as sacrificial template to synthesize graphene foam (GF) by chemical vapor deposition (CVD). ZnO NSAs were grown on the GF by hydrothermal synthesis to fabricate ZnO NSA/GF, which was used to detect dopamine in the presence of ascorbic acid and uric acid. The inter-connected ZnO NSAs with the sheet size of ~ 10 μm and thickness of ~ 500 nm uniformly distributed on the GF. The ZnO NSA/GF shows a sensitivity of 0.95 μA μM−1 in the concentration range of 0–80 μM and a measured limit of detection of 1 μM for determination of dopamine. Furthermore, the prepared electrode displays a reliable anti-interference to ascorbic acid and uric acid. It also shows an excellent reproducibility and long-time stability. The ZnO NSA/GF electrode was applied in human urine samples and exhibited satisfied recoveries.