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ecause this pandemic has an indirect impact on the onset and treatment of other conditions and on our global economy.
Amid a pandemic, vaccines represent a promising solution for mitigating public health and economic crises, and an improved understanding of individuals' vaccination intentions is crucial to design optimal immunization campaigns. This study predicts uptake rates for different COVID-19 vaccine specifications and identifies personal characteristics that moderate an individual's responsiveness to vaccine attributes.
We developed an online survey with contingent specifications of a COVID-19 vaccine, varying in effectiveness, risks of side effects, duration of immunity, and out-of-pocket cost. Using population-averaged logit models, we estimated vaccine uptake rates that account for uncertainty, heterogeneity across respondents, and interactions between vaccine and personal characteristics.
We obtained 3047 completed surveys. The highest uptake rate for an annual vaccine, 62%, is predicted when vaccine effectiveness is 80% to 90%, side effects are minimal, and the vaccine is provided at zero cost, with decreasholds. Although those concerned with COVID-19 will participate, further evidence is needed on how to incentivize participation among the unconcerned (43%) to prevent further pandemic spread.
In 2007, the American Heart Association published updated evidence-based guidelines on the recommended use of antibiotic prophylaxis to prevent viridans group streptococcal (VGS) infective endocarditis (IE) in cardiac patients undergoing invasive procedures. Ruboxistaurin datasheet The 2007 guidelines significantly scaled back the underlying conditions for which antibiotic prophylaxis was recommended, leaving only 4 categories thought to confer the highest risk of adverse outcome. The purpose of this update is to examine interval evidence of the acceptance and impact of the 2007 recommendations on VGS IE and, if needed, to make revisions based on this evidence.
A writing group was formed consisting of experts in prevention and treatment of infective endocarditis including members of the American Dental Association, the Infectious Diseases Society of America, and the American Academy of Pediatrics, in addition to the American Heart Association. MEDLINE database searches were done for English language articles on compliance with tfor categories of patients at highest risk for adverse outcome while emphasizing the critical role of good oral health and regular access to dental care for all. Randomized controlled studies to determine whether antibiotic prophylaxis is effective against VGS IE are needed to further refine recommendations.Detecting familial hypercholesterolemia (FH) early and "normalizing" low-density lipoprotein (LDL) cholesterol values are the 2 pillars for effective cardiovascular disease prevention in FH. Combining lipid-lowering therapies targeting synergistic/complementary metabolic pathways makes this feasible, even among severe phenotypes. For LDL receptor-dependent treatments, PCSK9 remains the main target for adjunctive therapy to statins and ezetimibe through a variety of approaches. These include protein inhibition (adnectins), inhibition of translation at mRNA level (antisense oligonucleotides or small interfering RNA), and creation of loss-of-function mutations through base-pair editing. For patients with little LDL receptor function, LDL receptor-independent treatment targeting ANGPTL3 through monoclonal therapies are now available, or in the future, antisense/small interfering RNA-based approaches offer alternative approaches. Finally, first-in-human studies are ongoing, testing adenovirus-mediated gene therapy transducing healthy LDLR DNA in patients with HoFH. Further development of the CRISPR cas technology, which has shown promising results in vivo on introducing PCSK9 loss-of-function mutations, will move a single-dose, curative treatment for FH closer.Emerging evidence suggests that elevated concentrations of triglyceride-rich lipoprotein remnants (TRLs) derived from hepatic and intestinal sources contribute to the risk of atherosclerotic cardiovascular events. Natural selection studies support a causal role for elevated concentrations of remnant cholesterol and the pathways contributing to perturbations in metabolic pathways regulating TRLs with an increased risk of atherosclerotic cardiovascular disease events. New therapies targeting select catalytic pathways in TRL metabolism reduce atherosclerosis in experimental models, and concentrations of TRLs in patients with a vast range of triglyceride levels. Clinical trials with inhibitors of angiopoietin-like 3 protein and apolipoprotein C-III will be required to provide further guidance on the potential contribution of these emerging therapies in the paradigm of cardiovascular risk management in patients with elevated remnant cholesterol.
Pivotal trials of chimeric antigen receptor T-cell (CAR-T) have identified common toxicities but may have been underpowered to detect cardiovascular and pulmonary adverse events (CPAEs).
This study sought to investigate CPAEs associated with commercial CD19-directed CAR-T therapy.
In this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify CPAEs associated with axicabtagene-ciloleucel and tisagenlecleucel. The authors evaluated disproportionate reporting by the reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC
>0 is deemed significant). Significant associations were further adjusted to age and sex (adj.ROR).
The authors identified CAR-T reports of 2,657 patients, including 546 CPAEs (20.5%). CPAEs overlapped with cytokine release syndrome in 68.3% (373 of 546) of the reports. Compared with the full database, CAR-T was associated with overreporting of tachyarrhythary assessment for and monitoring of CAR-T therapy recipients.
In this largest post-marketing study to date, the authors identified an association between CAR-T and various CPAEs, including tachyarrhythmias, cardiomyopathy, pericardial and pleural disorders, and VTEs. These findings should be considered in the multidisciplinary assessment for and monitoring of CAR-T therapy recipients.
The effects of nonphysiological flow generated by continuous-flow (CF) left ventricular assist devices (LVADs) on the aorta remain poorly understood.
The authors sought to quantify indexes of fibrosis and determine the molecular signature of post-CF-LVAD vascular remodeling.
Paired aortic tissue was collected at CF-LVAD implant and subsequently at transplant from 22 patients. Aortic wall morphometry and fibrillar collagen content (a measure of fibrosis) was quantified. In addition, whole-transcriptome profiling by RNA sequencing and follow-up immunohistochemistry were performed to evaluate CF-LVAD-mediated changes in aortic mRNA and protein expression.
The mean age was 52 ± 12 years, with a mean duration of CF-LVAD of 224 ± 193days (range 45-798days). There was a significant increase in the thickness of the collagen-rich adventitial layer from 218 ± 110μm pre-LVAD to 410 ± 209μm post-LVAD (P< 0.01). Furthermore, there was an increase in intimal and medial mean fibrillar collagen intensity from 22 ±o examine the contribution of nonphysiological flow patterns on vascular function and whether modulation of pulsatility may improve vascular remodeling and long-term outcomes.
Paclitaxel drug-coated devices (DCDs) were developed to improve lower extremity revascularization (LER) patency in peripheral artery disease (PAD) but have been associated with long-term mortality.
This study assessed DCD safety and effectiveness in LER for PAD.
VOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) randomized patients with PAD who underwent LER to rivaroxaban or placebo. The primary VOYAGER PAD study efficacy and safety outcomes were composite cardiovascular and limb events and Thrombolysis In Myocardial Infarction major bleeding. For prespecified DCD analyses, primary safety and effectiveness outcomes were mortality and unplanned index limb revascularization (UILR). Major adverse limb events (MALE) were a secondary outcome. Inverse probability treatment weighting was used to account for each subject's propensity for DCD treatment. Effects of rivaroxaban were assessed with Cox proportional ha PAD [VOYAGER PAD]; NCT02504216).
4,000 patients with PAD who underwent LER, DCDs were not associated with mortality or MALE but were associated with persistent reduction in UILR. These findings provide insight into the safety and effectiveness of DCDs in PAD. (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD [VOYAGER PAD]; NCT02504216).
Intraoperative arterial hypotension is strongly associated with postoperative major adverse cardiovascular events (MACE); however, whether targeting higher intraoperative mean arterial blood pressures (MAPs) may prevent adverse events remains unclear.
This study sought to determine whether targeting higher intraoperative MAP lowers the incidence of postoperative MACE.
This single-center randomized controlled trial assigned adult patients at cardiovascular risk undergoing major noncardiac surgery to an intraoperative MAP target of≥60mmHg (control) or≥75mmHg (MAP≥
). The primary outcome was acute myocardial injury on postoperative days 0-3 and/or 30-day MACE/acute kidney injury (AKI) (acute coronary syndrome, congestive heart failure, coronary revascularization, stroke, AKI, and all-cause mortality). The secondary outcome was 1-year MACE.
In total, 458 patients were randomized (intention-to-treat population 451). The cumulative intraoperative duration with MAP<65mmHg was significantly shorter in thelications. Despite a 60% reduction in hypotensive time with MAP less then 65 mm Hg, no significant reductions in acute myocardial injury or 30-day MACE/AKI could be found. (Biomarkers, Blood Pressure, BIS Risk Stratification/Management of Patients at Cardiac Risk in Major Noncardiac Surgery [BBB]; NCT02533128).As the SARS-CoV-2 pandemic continues to spread, the necessity for rapid, easy diagnostic capabilities could never have been more crucial. With this aim in mind, we have developed a cost-effective and time-saving testing methodology/strategy that implements a sensitive reverse transcriptase loop-mediated amplification (RT-LAMP) assay within narrow, commercially available and cheap, glass capillaries for detection of the SARS-CoV-2 viral RNA. The methodology is compatible with widely used laboratory-based molecular testing protocols and currently available infrastructure. It employs a simple rapid extraction protocol that lyses the virus, releasing sufficient genetic material for amplification. This extracted viral RNA is then amplified using a SARS-CoV-2 RT-LAMP kit, at a constant temperature and the resulting amplified product produces a colour change which can be visually interpreted. This testing protocol, in conjunction with the RT-LAMP assay, has a sensitivity of ∼100 viral copies per reaction of a sample and provides results in a little over 30 min.