Peripheral Arterial Disease: Incidence, Risk Factors, and Diagnosis

This dissertation includes three manuscripts related to peripheral arterial disease. The first examines the effects of assigned glycemic control strategy on the incidence of peripheral arterial disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. The BARI 2D results show that patients assigned to control their type 2 diabetes with a strategy that primarily used insulin sensitizing agents (metformin and/or thiazolidinediones) experienced fewer incident cases of peripheral arterial disease than patients assigned to a glycemic control strategy that primarily used insulin providing agents. The second manuscript extends this work by examining risk factors for peripheral arterial disease in the BARI 2D trial. The analyses included traditional cardiovascular risk factors as well as biomarkers indicative of inflammation, coagulation, and fibrinolysis. In patients treated with insulin sensitizing medications, biomarkers of inflammation and related processes were associated with lower extremity outcomes while this was not the case for patients treated with insulin providing medications, a useful mechanistic insight into how the different types of diabetes drugs may affect the progression of atherosclerosis. The third manuscript reports the results of a data collection project evaluating the reproducibility and reliability of two methods for measuring the ankle-brachial index. Reproducibility was excellent for Doppler-measured ABI, while the Colin oscillometric device showed moderate reproducibility. Agreement between Colin and Doppler was somewhat poor; therefore, we would not recommend the Colin device for measuring ABI in clinical settings. Each manuscript contributes uniquely to public health significance. The first suggests that a glycemic treatment strategy based on insulin sensitizers may reduce the progression of atherosclerosis in patients with type 2 diabetes. The second demonstrated that biomarkers of inflammation and fibrinolysis offer additional predictive value over traditional cardiovascular risk factors for incidence of PAD in type 2 diabetes patients treated with insulin sensitizing medications, implying that different types of glycemic control medications may have different mechanistic effects on the progression of atherosclerosis. The third reinforces current guidelines that Doppler ABI should remain the primary diagnostic for PAD in clinical and research settings

Statistical review of Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection : Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study)

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Mechanical circulatory support in acute myocardial infarction and cardiogenic shock: Challenges and importance of randomized control trials

BACKGROUND: Acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) is associated with significant morbidity and mortality. METHODS: We provide an overview of previously conducted studies on the use of mechanical circulatory support (MCS) devices in the treatment of AMI-CS and difficulties which may be encountered in conducting such trials in the United States. RESULTS: Well powered randomized control trials are difficult to conduct in a critically ill patient population due to physician preferences, perceived lack of equipoise and challenges obtaining informed consent. CONCLUSIONS: With growth in utilization of MCS devices in patients with AMI-CS, efforts to perform well-powered, randomized control trials must be undertaken

The Role of Race and Gender in Nutrition Habits and Self-Efficacy: Results from the Young Adult Weight Loss Study

Overweight and obesity are a massive public health problem and young adults are at high risk for gaining weight once they enter a college. This study sought to examine gender and race as they relate to nutrition habits and self-efficacy in a population of diverse young adults from the Young Adult Weight Loss Study. Participants ( = 62) were 29% males, 38.7% white, 33.8% Asian, and 12.9% African American. Males had lower self-efficacy for healthy eating (mean score = 92.5, SD = 17.1) compared to females (mean = 102.3, SD = 13.7, = 0.02). Males had higher consumption of sodium compared to females (4308 versus 3239 milligrams/day, = 0.01). There were no significant differences across racial subgroups in self-efficacy for healthy eating ( = 0.67) or self-efficacy for exercise ( = 0.61). Higher self-efficacy scores for healthy eating were significantly associated with less total sodium ( = −0.37, = 0.007), greater fruit consumption, and less saturated fat. Our results indicate that weight loss interventions should be individualized and that there may be specific areas to target that are different for men and women. Additional larger studies should be conducted to confirm if racial differences exist across nutrition habits and self-efficacy and to confirm gender differences noted in this study

Does Race Play a Role in Complications and Outcomes of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms?

BACKGROUND: Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of hematologic malignancies with known vascular complications. The role race and ethnicity play in these complications is less defined. We aimed to further evaluate the role of race in patients without a history of previous thrombotic or hemorrhagic events. METHODS: In this retrospective study, 300 adult patients with MPN were included; 270 (90.0%) were White and 30 (10.0%) were non-White. The non-White group primarily consisted of African American or Black (26 patients), followed by others. Median age at diagnosis was 58 years for White patients and 61.5 years for non-White patients. The interaction between outcomes and vascular events with race was evaluated using multivariate logistical regression models. RESULTS: The incidence of thrombotic events was inversely correlated with age at diagnosis, with younger patients demonstrating a higher rate of thrombotic events over time (p < .001). The incidence of thrombotic or hemorrhagic events did not differ between White and non-White patients. A statistically significant difference in median survival was observed between White and non-White patients: 29 years (95% confidence interval [CI]: 21.8-not reached) versus 13 years (95% CI: 5.7-22.7), respectively (p = .016). CONCLUSION: This study did not find a significant difference in the rate of thrombotic or hemorrhagic events between White and non-White patients with MPN but suggested that non-White patients had significantly shorter median survival than White patients. Such observations may inform future studies to further characterize racial disparities in outcomes

The Biosurveillance Analytics Resource Directory (BARD): Facilitating the Use of Epidemiological Models for Infectious Disease Surveillance

Epidemiological modeling for infectious disease is important for disease management and its routine implementation needs to be facilitated through better description of models in an operational context. A standardized model characterization process that allows selection or making manual comparisons of available models and their results is currently lacking. A key need is a universal framework to facilitate model description and understanding of its features. Los Alamos National Laboratory (LANL) has developed a comprehensive framework that can be used to characterize an infectious disease model in an operational context. The framework was developed through a consensus among a panel of subject matter experts. In this paper, we describe the framework, its application to model characterization, and the development of the Biosurveillance Analytics Resource Directory (BARD; http://brd.bsvgateway.org/brd/), to facilitate the rapid selection of operational models for specific infectious/communicable diseases. We offer this framework and associated database to stakeholders of the infectious disease modeling field as a tool for standardizing model description and facilitating the use of epidemiological models

Publisher Correction: Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI (Nature Medicine, (2022), 28, 5, (924-933), 10.1038/s41591-022-01772-9)

In the version of this article initially published, a list of the DECIDE-AI expert group members and their affiliations was omitted and has now been included in the HTML and PDF versions of the article. *A list of authors and their affiliations appears online

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline