The COVID-19 pandemic began in early 2020 with major health consequences. While a need to disseminate information to the medical community and general public was paramount, concerns have been raised ...regarding the scientific rigor in published reports. We performed a systematic review to evaluate the methodological quality of currently available COVID-19 studies compared to historical controls. A total of 9895 titles and abstracts were screened and 686 COVID-19 articles were included in the final analysis. Comparative analysis of COVID-19 to historical articles reveals a shorter time to acceptance (13.0IQR, 5.0-25.0 days vs. 110.0IQR, 71.0-156.0 days in COVID-19 and control articles, respectively; p < 0.0001). Furthermore, methodological quality scores are lower in COVID-19 articles across all study designs. COVID-19 clinical studies have a shorter time to publication and have lower methodological quality scores than control studies in the same journal. These studies should be revisited with the emergence of stronger evidence.
Despite advances in our understanding of the pathophysiology and the management of pulmonary arterial hypertension (PAH), significant therapeutic gaps remain for this devastating disease. Yet, few ...innovative therapies beyond the traditional pathways of endothelial dysfunction have reached clinical trial phases in PAH. Although there are inherent limitations of the currently available models of PAH, the leaky pipeline of innovative therapies relates, in part, to flawed preclinical research methodology, including lack of rigour in trial design, incomplete invasive hemodynamic assessment, and lack of careful translational studies that replicate randomized controlled trials in humans with attention to adverse effects and benefits. Rigorous methodology should include the use of prespecified eligibility criteria, sample sizes that permit valid statistical analysis, randomization, blinded assessment of standardized outcomes, and transparent reporting of results. Better design and implementation of preclinical studies can minimize inherent flaws in the models of PAH, reduce the risk of bias, and enhance external validity and our ability to distinguish truly promising therapies form many false-positive or overstated leads. Ideally, preclinical studies should use advanced imaging, study several preclinical pulmonary hypertension models, or correlate rodent and human findings and consider the fate of the right ventricle, which is the major determinant of prognosis in human PAH. Although these principles are widely endorsed, empirical evidence suggests that such rigor is often lacking in pulmonary hypertension preclinical research. The present article discusses the pitfalls in the design of preclinical pulmonary hypertension trials and discusses opportunities to create preclinical trials with improved predictive value in guiding early-phase drug development in patients with PAH, which will need support not only from researchers, peer reviewers, and editors but also from academic institutions, funding agencies, and animal ethics authorities.
The Evolution of Coronary Stents: A Brief Review Simard, Trevor, MD; Hibbert, Benjamin, MD, PhD; Ramirez, F. Daniel, MD ...
Canadian journal of cardiology,
2014, January 2014, 2014-Jan, 2014-1-00, 20140101, Letnik:
30, Številka:
1
Journal Article
Recenzirano
Abstract Percutaneous coronary intervention is the most prevalent method for coronary artery revascularization. Initial interventions using balloon angioplasty had limited efficacy because coronary ...dissections, arterial recoil, and neointimal formation led to high rates of abrupt vessel closure and clinical restenosis. With the introduction of coronary stents, vascular dissections were stabilized and arterial recoil was eliminated, but neointimal accumulation remained problematic, resulting in the development of in-stent restenosis (ISR) in 20%-30% of cases. Drug-eluting stents (DESs) were developed to release antiproliferative agents at the site of arterial injury to attenuate neointimal formation. Although DESs have incrementally improved outcomes after percutaneous coronary intervention, delayed re-endothelialization and stent thrombosis remain important challenges. Herein we review the pathophysiology of ISR, stent thrombosis, and briefly summarize the clinical evidence behind first- and second-generation DESs. Moreover, we discuss advancements in our understanding of the pathogenesis of ISR and potential novel therapeutic strategies to improve clinical outcomes.
Rationale:Methodological sources of bias and suboptimal reporting contribute to irreproducibility in preclinical science and may negatively affect research translation. Randomization, blinding, ...sample size estimation, and considering sex as a biological variable are deemed crucial study design elements to maximize the quality and predictive value of preclinical experiments.Objective:To examine the prevalence and temporal patterns of recommended study design element implementation in preclinical cardiovascular research.Methods and Results:All articles published over a 10-year period in 5 leading cardiovascular journals were reviewed. Reports of in vivo experiments in nonhuman mammals describing pathophysiology, genetics, or therapeutic interventions relevant to specific cardiovascular disorders were identified. Data on study design and animal model use were collected. Citations at 60 months were additionally examined as a surrogate measure of research impact in a prespecified subset of studies, stratified by individual and cumulative study design elements. Of 28 636 articles screened, 3396 met inclusion criteria. Randomization was reported in 21.8%, blinding in 32.7%, and sample size estimation in 2.3%. Temporal and disease-specific analyses show that the implementation of these study design elements has overall not appreciably increased over the past decade, except in preclinical stroke research, which has uniquely demonstrated significant improvements in methodological rigor. In a subset of 1681 preclinical studies, randomization, blinding, sample size estimation, and inclusion of both sexes were not associated with increased citations at 60 months.Conclusions:Methodological shortcomings are prevalent in preclinical cardiovascular research, have not substantially improved over the past 10 years, and may be overlooked when basing subsequent studies. Resultant risks of bias and threats to study validity have the potential to hinder progress in cardiovascular medicine as preclinical research often precedes and informs clinical trials. Stroke research quality has uniquely improved in recent years, warranting a closer examination for interventions to model in other cardiovascular fields.
Post-operative atrial fibrillation (POAF) is a frequent cardiothoracic surgery complication that increases hospital stay, mortality and costs. Despite decades of research, there has been no ...systematic overview and meta-analysis of preclinical therapies for POAF in animal models.
We performed a systematic search of MEDLINE and EMBASE from their inception through September 2020 to determine the effect of preclinical POAF therapies on primary efficacy outcomes using a prospectively registered protocol (CRD42019155649). Bias was assessed using the SYRCLE tool and CAMARADES checklist.
Within the 26 studies that fulfilled our inclusion criteria, we identified 4 prevention strategies including biological (n = 5), dietary (n = 2), substrate modification (n = 2), and pharmacological (n = 17) interventions targeting atrial substrate, cellular electrophysiology or inflammation. Only one study altered more than 1 pathophysiological mechanism. 73% comprised multiple doses of systemic therapies. Large animal models were used in 81% of the studies. Preclinical therapies altogether attenuated atrial fibrosis (SMD -2.09; 95% confidence interval CI -2.95 to -1.22; p < 0.00001; I2 = 47%), AF inducibility (RR 0.40; 95% CI 0.21 to 0.79; p = 0.008; I2 = 39%), and AF duration (SMD -2.19; 95% CI -3.05 to -1.32; p < 0.00001; I2 = 50%). However, all the criteria needed to evaluate the risk of bias was unclear for many outcomes and only few interventions were independently validated by more than 1 research group.
Treatments with therapies targeting atrial substrate, cellular electrophysiology or inflammation reduced POAF in preclinical animal models compared to controls. Improving the quality of outcome reporting, independently validating promising approaches and targeting complimentary drivers of POAF are promising means to improve the clinical translation of novel therapies for this highly prevalent and clinically meaningful disease.
New-onset atrial fibrillation (NOAF) is commonly encountered in critically ill adults. Evidence evaluating the association between NOAF and patient-important outcomes in this population is ...conflicting. Furthermore, little is known regarding the association between NOAF and resource use or hospital costs.
Retrospective analysis (2011-2016) of a prospectively collected registry from two Canadian hospitals of consecutive ICU patients aged ≥ 18 years. We excluded patients with a known history of AF prior to hospital admission. Any occurrence of atrial fibrillation (AF) was prospectively recorded by bedside nurses. The primary outcome was hospital mortality, and we used multivariable logistic regression to adjust for confounders. We used a generalized linear model to evaluate contributors to total cost.
We included 15,014 patients, and 1541 (10.3%) had NOAF during their ICU admission. While NOAF was not associated with increased odds of hospital death among the entire cohort (adjusted odds ratio aOR 1.02 95% confidence interval CI 0.97-1.08), an interaction was noted between NOAF and sepsis, and the presence of both was associated with higher odds of hospital mortality (aOR 1.28 95% CI 1.09-1.36) than either alone. Patients with NOAF had higher total costs (cost ratio CR 1.09 95% CI 1.02-1.20). Among patients with NOAF, treatment with a rhythm-control strategy was associated with higher costs (CR 1.24 95% CI 1.07-1.40).
While NOAF was not associated with death or requiring discharge to long-term care among critically ill patients, it was associated with increased length of stay in ICU and increased total costs.
Background:Transcatheter aortic valve implantation (TAVI) has become the standard of care for management of high-risk patients with aortic stenosis. Limited data is available regarding the ...performance of TAVI in patients with native aortic valve regurgitation (NAVR).Methods and Results:We performed a systematic review from 2002 to 2016. The primary outcome was device success as per VARC-2 criteria. Secondary endpoints included procedural complications, and 30-day and 1-year mortality rates. A total of 175 patients were included from 31 studies. Device success was reported in 86.3% of patients – with device failure driven by moderate aortic regurgitation (AR ≥3+) and/or need for a second device. Procedural complications were rare, with no procedural deaths, myocardial infarctions or annular ruptures reported. Procedural safety was acceptable with a low 30-day incidence of stroke (1.5%). The 30-day and 1-year overall mortality rates were 9.6% and 20.0% (cardiovascular death, 3.8% and 10.1%, respectively). Patients receiving 2nd-generation valves demonstrated similar safety profiles with greater device success compared with 1st-generation valves (96.2% vs. 78.4%). This was driven by the higher incidence of second-valve implantation (23.4% vs. 1.7%) and significant paravalvular leak (8.3% vs. 0.0%).Conclusions:TAVI demonstrates acceptable safety and efficacy in high-risk patients with severe NAVR. Second-generation valves may afford a similar safety profile with improved device success. Dedicated studies are needed to definitively establish the efficacy of TAVI in this population.
Small studies have implicated plasminogen activator inhibitor-1 (PAI-1) as a predictor of cardiovascular events; however, these findings have been inconsistent.We sought out to examine the potential ...role of PAI-1 as a marker for major adverse cardiovascular events (MACE).
We systematically reviewed all indexed studies examining the association between PAI-1 and MACE (defined as death, myocardial infarction, or cerebrovascular accident) or restenosis. EMBASE, Web of Science, Medline, and the Cochrane Library were searched through October 2016 to identify relevant studies, supplemented by letters to authors and review of citations. Studies reporting the results of PAI-1 antigen and/or activity levels in association with MACE in human subjects were included.
Of 5961 articles screened, we identified 38 articles published between 1991 to 2016 that reported PAI-1 levels in 11,557 patients. In studies that examined PAI-1 antigen and activity levels, 15.1% and 29.6% of patients experienced MACE, respectively. Patients with MACE had higher PAI-1 antigen levels with a mean difference of 6.11 ng/mL (95% CI, 3.27-8.96). This finding was similar among patients with and without known coronary artery disease. Comparatively, studies that stratified by PAI-1 activity levels were not associated with MACE. In contrast, studies of coronary restenosis suggest PAI-1 antigen and activity levels are negatively associated with MACE.
Elevated plasma PAI-1 antigen levels are associated with MACE. Definitive studies are needed to ascertain if PAI-1 acts simply as a marker of risk or if it is indeed a bona fide therapeutic target.
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