Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Evaluation of Heavy Metal and Microbial Contamination in Green Tea and Herbal Tea Used for Weight Loss in the Palestinian Market

The use of green tea and herbal tea for weight loss is increasing worldwide owing to the rising rates of obesity. There are concerns about the safety and quality of these herbal products owing to their increased consumption worldwide. In this study, we evaluated randomly collected samples of green tea and herbal tea and tested them for heavy metal and microbial contamination. Eighteen samples of green tea or herbal tea of widely used brands in Palestine were tested for heavy metal and microbial contamination. The results showed that 7 of the samples had toxic heavy metals such as chromium (Cr) and lead (Pb), and their concentrations were above the allowable limits set by the World Health Organization (WHO). Moreover, 6 of the samples that were tested had microbial contamination with high total aerobic microbial count (TAMC) and total yeast and mold count (TYMC). This could be due to improper handling and storage conditions of these herbal products. This study is the first of its kind in Palestine, and its results are forewarning to all the responsible authorities, including the Ministry of Health (MoH), to take immediate corrective actions such as quality control testing, auditing, and registration of marketed tea products

Minimally invasive surgery versus transcatheter aortic valve replacement: a systematic review and meta-analysis

Transcatheter aortic valve replacement (TAVR) has recently been approved for use in patients who are at intermediate and low surgical risk. Moreover, recent years have witnessed a renewed interest in minimally invasive aortic valve replacement (miAVR). The present meta-analysis compared the outcomes of TAVR and miAVR in the management of aortic stenosis (AS). We conducted an electronic search across six databases from 2002 (TAVR inception) to December 2019. Data from relevant studies regarding the clinical and length of hospitalisation outcomes were extracted and analysed using R software. We identified a total of 11 cohort studies, of which seven were matched/propensity matched. Our analysis demonstrated higher rates of midterm mortality (≥1 year) with TAVR (risk ratio (RR): 1.93, 95% CI: 1.16 to 3.22), but no significant differences with respect to 1 month mortality (RR: 1.00, 95% CI: 0.55 to 1.81), stroke (RR: 1.08, 95% CI: 0.40 to 2.87) and bleeding (RR: 1.45, 95% CI: 0.56 to 3.75) rates. Patients undergoing TAVR were more likely to experience paravalvular leakage (RR: 14.89, 95% CI: 6.89 to 32.16), yet less likely to suffer acute kidney injury (RR: 0.38, 95% CI: 0.21 to 0.69) compared with miAVR. The duration of hospitalisation was significantly longer in the miAVR group (mean difference: 1.92 (0.61 to 3.24)). Grading of Recommendations Assessment, Development and Evaluation assessment revealed ≤moderate quality of evidence in all outcomes. TAVR was associated with lower acute kidney injury rate and shorter length of hospitalisation, yet higher risks of midterm mortality and paravalvular leakage. Given the increasing adoption of both techniques, there is an urgent need for head-to-head randomised trials with adequate follow-up periods

Factors associated with sex disparities in leisure-time physical activity: An analysis of the behavioral risk factor surveillance system, 2011 to 2021

Objective: To identify whether sex disparities in leisure-time physical activity (LTPA) vary across population subgroups.Participants and methods: We used data from the Behavioral Risk Factor Surveillance System (BRFSS) spanning 2011 to 2021. We examined subgroups by age, race/ethnicity, income, employment, education, marital status, body mass index, and cardiometabolic comorbidities (diabetes, hypertension, and cardiovascular disease) to identify where sex disparities in LTPA are most pronounced.Results: Among 4,415,992 respondents (57.4% [2,533,234] women and 42.6% [1,882,758] men), women were less likely than men to report LTPA (73.0% vs 76.8%; odds ratio [OR], 0.817; 95% CI, 0.809 to 0.825). The gap was widest between the youngest (OR for the 18- to 24-year age group, 0.71; 95% CI, 0.68 to 0.74) and oldest (OR for the 80 years or older age group, 0.71; 95% CI, 0.69 to 0.73) respondents but was narrower between middle-aged adults (OR for the 50- to 59-year age group, 0.95; 95% CI, 0.93 to 0.97). Disparity was greater among non-Hispanic Black participants (OR, 0.70; 95% CI, 0.68 to 0.72) and Hispanic participants (OR, 0.79; 95% CI, 0.77 to 0.81) than among non-Hispanic White participants (OR, 0.85; 95% CI, 0.84 to 0.86). Disparities were greater at the lowest income levels (OR, 0.81; 95% CI, 0.78 to 0.85) and lower at the highest income levels (OR, 0.94; 95% CI, 0.91 to 0.96). The disparity was greater in unemployed individuals (OR, 0.78; 95% CI, 0.76 to 0.80) compared with employed individuals (OR, 0.91; 95% CI, 0.90 to 0.92). Moreover, disparity was greater in individuals with a body mass index in the overweight or obese range and those with diabetes, hypertension, or cardiovascular disease.Conclusion: Women are less likely than men to engage in LTPA. These disparities are greatest among the young and elderly, Black and Hispanic individuals, lower income and unemployed individuals, and individuals with cardiometabolic disease. Targeted interventions are needed to reduce sex-related disparities

The underutilization of preventive cardiovascular measures in patients with cancer: An analysis of the behavioural risk factor surveillance system, 2011-2022

Aims: To characterize the influence of a cancer diagnosis on the use of preventive cardiovascular measures in patients with and without cardiovascular disease (CVD).Methods: Data from the Behavioural Risk Factor Surveillance System Survey (spanning 2011 to 2022) were used. Multivariable logistic regression models adjusted for potential confounders were applied to calculate average marginal effects (AME), the average difference in the probability of using a given therapy between patients with and without cancer. Outcomes of interest included the use of pharmacological therapies, physical activity, smoking cessation, and post-CVD rehabilitation.Results: Among 5,012,721 respondents, 579,114 reported a history of CVD (coronary disease or stroke), and 842,221 reported a diagnosis of cancer. The association between cancer and the use of pharmacological therapies varied between those with versus without CVD (p-value for interaction: \u3c0.001). Among patients with CVD, a cancer diagnosis was associated with a lower use of blood pressure-lowering medications (AME: -1.46% [95% CI: -2.19 to -0.73%]), lipid-lowering medications (AME: -2.34% [95% CI: -4.03 to -0.66%]), and aspirin (AME: -6.05% [95% CI: -8.88 to -3.23%]). Among patients without CVD, there were no statistically significant differences between patients with and without cancer regarding pharmacological therapies. Additionally, cancer was associated with a significantly lower likelihood of engaging in physical activity in the overall cohort, and in using post-CVD rehabilitation regimens, particularly post-stroke rehabilitation.Conclusions: Preventive pharmacological agents are underutilized in those with cancer and concomitant CVD, and physical activity is underutilized in patients with cancer in those with or without CVD

The underutilization of preventive cardiovascular measures in patients with cancer: An analysis of the behavioural risk factor surveillance system, 2011-22

Aims: This study aimed to characterize the influence of a cancer diagnosis on the use of preventive cardiovascular measures in patients with and without cardiovascular disease (CVD). Methods and results: Data from the Behavioural Risk Factor Surveillance System Survey (spanning 2011-22) were used. Multivariable logistic regression models adjusted for potential confounders were applied to calculate average marginal effects (AME), the average difference in the probability of using a given therapy between patients with and without cancer. Outcomes of interest included the use of pharmacological therapies, physical activity, smoking cessation, and post-CVD rehabilitation. Among 5 012 721 respondents, 579 114 reported a history of CVD (coronary disease or stroke), and 842 221 reported a diagnosis of cancer. The association between cancer and the use of pharmacological therapies varied between those with vs. without CVD (P-value for interaction: Conclusion: Preventive pharmacological agents are underutilized in those with cancer and concomitant CVD, and physical activity is underutilized in patients with cancer in those with or without CVD. Lay summary: •This paper compared the use of preventive cardiovascular measures, both pharmaceutical and non-pharmaceutical, in patients with and without cancer.•In patients with cardiovascular disease and cancer, there is a lower use of preventive cardiovascular medications compared with those with cardiovascular disease but without cancer. This includes a lower utilization of blood pressure-lowering medications, cholesterol-lowering medications, and aspirin.•Patients with cancer reported lower levels of exercise but higher levels of smoking cessation compared with those without cance

Willingness of Healthcare Workers to Recommend or Receive a Third COVID-19 Vaccine Dose: A Cross-Sectional Study from Jordan

Background: The availability of COVID-19 vaccines worldwide necessitates measuring healthcare workers’ (HCWs’) willingness to recommend or receive these vaccines. Therefore, we conducted a local study in Jordan to assess HCWs’ willingness to recommend or receive a third dose of a COVID-19 vaccine and the predictors of such a decision. A cross-sectional study investigated Jordanian HCWs’ willingness regarding a third dose of a COVID-19 vaccine using a self-administered online questionnaire through WhatsApp, a mobile phone application. A total of 300 HCWs participated in the current study. Of these HCWs, 65.3% were physicians, 25.3% were nurses, and 9.3% were pharmacists. HCWs’ overall willingness regarding a third vaccine dose was 68.4% (49.4% certainly and 19.0% probably), whereas the overall willingness of HCWs to recommend a third dose to their patients was 73.3% (49.0% certainly and 24.3% probably). Males had significantly higher willingness than females (82.1% vs. 60.1%, p < 0.05). Physicians reported more willingness than nurses and pharmacists. HCWs’ willingness was not significantly affected by direct contact with a patient infected with COVID-19 or by a personal history of COVID-19 infection. Only 31% of HCWs were certainly willing to recommend the vaccine to their patients with chronic diseases, and only 28% of the participants were certainly willing to recommend it to people aged 65 or older. HCWs’ willingness to receive a third dose of a COVID-19 vaccine is limited in Jordan. This has affected their certainty in recommending this vaccine to their patients or people older than 60. Decision-makers and health-promotion programs in Jordan should focus on addressing this public health problem

Cardiovascular toxicities associated with bispecific T-cell engager therapy.

BACKGROUND: Bispecific T-cell engagers (BTEs) are novel agents used to treat hematological malignancies. Early trials were underpowered to define cardiovascular adverse events (CVAE) and no large-scale studies systematically examined the CVAEs associated with BTEs. METHODS: Leveraging the US Food and Drug Administrations Adverse Event Reporting System-(FAERS), we identified the relative frequency of CVAEs after initiation of five BTE products approved by the Food and Drug Administration between 2014 and 2023 for the treatment of hematological malignancies. Adjusted reporting ORs (aROR) were used to identify disproportionate reporting of CVAEs with BTEs compared with background rates in the database. Fatality rates and risk ratios (RRs) for each adverse event (AE) were calculated. RESULTS: From 3668 BTE-related cases reported to FAERS, 747 (20.4%) involved CVAEs. BTEs as a class were associated with fatal CVAEs (aROR 1.29 (95% CI 1.12 to 1.50)), an association mainly driven by teclistamab (aROR 2.44 (95% CI 1.65 to 3.60)). Teclistamab was also associated with a disproportionate risk of myocarditis (aROR 25.70 (95% CI 9.54 to 69.23)) and shock (aROR 3.63 (95% CI 2.30 to 5.74)), whereas blinatumomab was associated with a disproportionate risk of disseminated intravascular coagulation (aROR 3.02 (95% CI 1.98 to 4.60)) and hypotension (aROR 1.59 (95% CI 1.25 to 2.03)). CVAEs were more fatal compared with non-CVAEs (31.1% vs 17.4%; RR 1.76 (95% CI 1.54 to 2.03)). Most CVAEs (83.3%) did not overlap with cytokine release syndrome. CONCLUSION: In the first postmarketing surveillance study of BTEs, CVAEs were involved in approximately one in five AE reports and carried a significant mortality risk

Neural stem cell-based therapies and glioblastoma management: current evidence and clinical challenges

Gliomas, which account for nearly a quarter of all primary CNS tumors, present significant contemporary therapeutic challenges, particularly the highest-grade variant (glioblastoma multiforme), which has an especially poor prognosis. These difficulties are due to the tumor’s aggressiveness and the adverse effects of radio/chemotherapy on the brain. Stem cell therapy is an exciting area of research being explored for several medical issues. Neural stem cells, normally present in the subventricular zone and the hippocampus, preferentially migrate to tumor masses. Thus, they have two main advantages: They can minimize the side effects associated with systemic radio/chemotherapy while simultaneously maximizing drug delivery to the tumor site. Another feature of stem cell therapy is the variety of treatment approaches it allows. Stem cells can be genetically engineered into expressing a wide variety of immunomodulatory substances that can inhibit tumor growth. They can also be used as delivery vehicles for oncolytic viral vectors, which can then be used to combat the tumorous mass. An alternative approach would be to combine stem cells with prodrugs, which can subsequently convert them into the active form upon migration to the tumor mass. As with any therapeutic modality still in its infancy, much of the research regarding their use is primarily based upon knowledge gained from animal studies, and a number of ongoing clinical trials are currently investigating their effectiveness in humans. The aim of this review is to highlight the current state of stem cell therapy in the treatment of gliomas, exploring the different mechanistic approaches, clinical applicability, and the existing limitations