Faculty Bibliography

BACKGROUND:It is important to monitor the scope of clinical research of all types, to involve participants of all ages and subgroups in studies that are appropriate to their condition, and to ensure equal access and broad validity of the findings. OBJECTIVE:We conducted a review of clinical research performed at New York University with the following objectives: (1) to determine the utility of institutional administrative data to characterize clinical research activity; (2) to assess the inclusion of special populations; and (3) to determine if the type, initiation, and completion of the study differed by age. METHODS:Data for all studies that were institutional review board-approved between January 1, 2014, and November 2, 2016, were obtained from the research navigator system, which was launched in November 2013. One module provided details about the study protocol, and another module provided the characteristics of individual participants. Research studies were classified as observational or interventional. Descriptive statistics were used to assess the characteristics of clinical studies across the lifespan, by type, and over time. RESULTS:A total of 22%-24% of studies included children (minimum age <18 years) and 4%-5% focused exclusively on pediatrics. Similarly, 64%-72% of studies included older patients (maximum age >65 years) but only 5%-12% focused exclusively on geriatrics. Approximately 85% of the studies included both male and female participants. Of the remaining studies, those open only to girls or women were approximately 3 times as common as those confined to boys or men. A total of 56%-58% of projects focused on nonvulnerable patients. Among the special populations studied, children (12%-15%) were the most common. Noninterventional trial types included research on human data sets (24%), observational research (22%), survey research (16%), and biospecimen research (8%). The percentage of projects designed to test an intervention in a vulnerable population increased from 17% in 2014 to 21% in 2015. CONCLUSIONS:Pediatric participants were the special population that was most often studied based on the number of registered projects that included children and adolescents. However, they were much less likely to be successfully enrolled in research studies compared with adults older than 65 years. Only 20% of the studies were interventional, and 20%-35% of participants in this category were from vulnerable populations. More studies are exclusively devoted to women's health issues compared with men's health issues.

OBJECTIVE:<0.001). Rates of adverse events increased with the magnitude of D-dimer elevation; individuals with presenting D-dimer >2000 ng/mL had the highest risk of critical illness (66%), thrombotic event (37.8%), acute kidney injury (58.3%), and death (47%). CONCLUSIONS:Abnormal D-dimer was frequently observed at admission with COVID-19 and was associated with higher incidence of critical illness, thrombotic events, acute kidney injury, and death. The optimal management of patients with elevated D-dimer in COVID-19 requires further study.

Background/UNASSIGNED:There is increasing recognition of a prothrombotic state in COVID-19. Post-mortem examination can provide important mechanistic insights. Methods/UNASSIGNED:We present a COVID-19 autopsy series including findings in lungs, heart, kidneys, liver, and bone, from a New York academic medical center. Findings/UNASSIGNED: = 2). Platelet-rich peri‑tubular fibrin microthrombi were a prominent renal feature. Acute tubular necrosis, and red blood cell and granular casts were seen in multiple cases. Significant glomerular pathology was notably absent. Numerous platelet-fibrin microthrombi were identified in hepatic sinusoids. All lungs exhibited diffuse alveolar damage (DAD) with a spectrum of exudative and proliferative phases including hyaline membranes, and pneumocyte hyperplasia, with viral inclusions in epithelial cells and macrophages. Three cases had superimposed acute bronchopneumonia, focally necrotizing. Interpretation/UNASSIGNED:In this series of seven COVID-19 autopsies, thrombosis was a prominent feature in multiple organs, in some cases despite full anticoagulation and regardless of timing of the disease course, suggesting that thrombosis plays a role very early in the disease process. The finding of megakaryocytes and platelet-rich thrombi in the lungs, heart and kidneys suggests a role in thrombosis. Funding/UNASSIGNED:None.

Background: Revascularization is often performed in patients with stable ischemic heart disease (SIHD). However, whether revascularization reduces death and other cardiovascular outcomes is uncertain. Methods: We conducted PUBMED/EMBASE/CENTRAL searches for randomized trials comparing routine revascularization versus an initial conservative strategy in patients with SIHD. The primary outcome was death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), heart failure, stroke, unstable angina and freedom from angina. Trials were stratified by percent stent use and by percent statin use to evaluate outcomes in contemporary trials. Results: Fourteen RCTs that enrolled 14,877 patients followed up for a weighted mean of 4.5 years with 64,678 patient years of follow-up fulfilled our inclusion criteria. Most trials enrolled patients with preserved left ventricular systolic function, low symptom burden and excluded patients with left main disease. Revascularization compared with medical therapy alone was not associated with a reduced risk of death (RR=0.99, 95% CI 0.90-1.09). Trial sequential analysis showed that the cumulative z-curve crossed the futility boundary indicating firm evidence for lack of a 10% or greater reduction in death. Revascularization was associated with a reduced non-procedural MI (RR=0.76, 95% CI 0.67-0.85) but also with increased procedural MI (RR=2.48, 95% CI 1.86-3.31) with no difference in overall MI (RR=0.93, 95% CI 0.83-1.03). A significant reduction in unstable angina (RR=0.64, 95% CI 0.45-0.92) and increase in freedom from angina (RR=1.10, 95% CI 1.05-1.15) was also observed with revascularization. There were no treatment-related differences in the risk of heart failure or stroke. Conclusions: In patients with SIHD, routine revascularization was not associated with improved survival, but was associated with a lower risk of non-procedural MI and unstable angina with greater freedom from angina at the expense of higher rates of procedural MI. Longer-term follow-up of trials is needed to assess whether reduction in these non-fatal spontaneous events improves long-term survival.

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented challenge and opportunity for translational investigators to rapidly develop safe and effective therapeutic interventions. Greater risk of severe disease in COVID-19 patients with comorbid diabetes mellitus, obesity, and heart disease may be attributable to synergistic activation of vascular inflammation pathways associated with both COVID-19 and cardiometabolic disease. This mechanistic link provides a scientific framework for translational studies of drugs developed for treatment of cardiometabolic disease as novel therapeutic interventions to mitigate inflammation and improve outcomes in patients with COVID-19.

Air pollution is a major contributor to cardiovascular morbidity and mortality. Fine particulate matter <2.5 µm in diameter may be a modifiable risk factor for hypertension. The benefits of in-home air filtration on systolic blood pressure (BP) and diastolic BP are unclear. To examine the effects of in-home personal air cleaner use on fine particulate exposure and BP, we queried PubMed, Web of Science, Cochrane Central Register, Inspec, and EBSCO GreenFILE databases for relevant clinical trials. Included studies were limited to nonsmoking participants in smoke-free homes with active or sham filtration on indoor fine particulate concentrations and changes in systolic and diastolic BP. Of 330 articles identified, 10 trials enrolling 604 participants who met inclusion criteria were considered. Over a median 13.5 days, there was a significant reduction of mean systolic BP by ≈4 mm Hg (-3.94 mm Hg [95% CI, -7.00 to -0.89]; P=0.01) but a nonsignificant difference in mean diastolic BP (-0.95 mm Hg [95% CI, -2.81 to 0.91]; P=0.32). Subgroup analyses indicated no heterogeneity of effect by age, level of particulate exposure, or study duration. Given the variation in study design, additional study is warranted to confirm and better quantify the observed benefits in systolic BP found with personal air cleaner use.