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Background and Purpose: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective of this study is to describe multidimensional outcomes, identify predictors of worse outcomes, and explore the effect of thrombolysis in this population. Methods: This prospective observational study included patients with ischemic stroke or transient ischemic attack, a baseline National Institutes of Health Stroke Scale (NIHSS) score 0 to 5, presenting within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale score of 0 to 1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16, and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. Results: A total of 1765 participants were included from 100 Get With The Guidelines-Stroke participating hospitals (age, 65±14; 42% women; final diagnosis of ischemic stroke, 90%; transient ischemic attack, 10%; 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid recipients, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, and extremity weakness. Similar outcomes were noted for the alteplase-treated and untreated groups. Alteplase-treated patients were younger (64±13 versus 67±1.4) with higher NIHSS (2.9±1.4 versus 1.7±1.4). After adjusting for age, sex, race/ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an association with Stroke Impact Scale-16 in the restricted sample of baseline NIHSS score 3–5. Few symptomatic intracerebral hemorrhages were recorded ( Conclusions: A large proportion of stroke patients presenting with low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort, but a suggestion of efficacy was noted in the NIHSS 3–5 subgroup. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02072681.

Background and Purpose: Studies suggest an increased risk of adverse outcomes among patients with acute ischemic stroke (AIS) and coronavirus disease 2019 (COVID-19). Methods: Using Get With The Guidelines–Stroke, we identified 41 971 patients (AIS/COVID-19: 1143; AIS/no COVID-19: 40 828) with AIS hospitalized between February 4, 2020 and June 29, 2020, from 458 Get With The Guidelines–Stroke hospitals with at least one COVID-19 case and evaluated clinical characteristics, treatment patterns, and outcomes. Results: Compared with patients with AIS/no COVID-19, those with AIS/COVID-19 were younger, more likely to be non-Hispanic Black, Hispanic, or Asian, more likely to present with higher National Institutes of Health Stroke Scale scores, and had greater proportions of large vessel occlusions. Rates of thrombolysis and thrombectomy were similar between the groups. Door to computed tomography (median 55 [18–207] versus 35 [14–99] minutes, P P P =0.002) times were longer in the AIS/COVID-19 cohort. In adjusted models, patients with AIS/COVID-19 had decreased odds of discharge with modified Rankin Scale score of ≤2 (odds ratio, 0.65 [95% CI, 0.52–0.81], P P ConclusionS: This analysis demonstrates younger age, greater stroke severity, longer times to evaluation and treatment, and worse morbidity and mortality in patients with AIS/COVID-19 compared with those with AIS/no COVID-19.

Background and Purpose: Clinical fluctuations in ischemic stroke symptoms are common, but fluctuations before hospital arrival have not been previously characterized. Methods: A standardized qualitative assessment of fluctuations before hospital arrival was obtained in an observational study that enrolled patients with mild ischemic stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score of 0–5) present on arrival to hospital within 4.5 hours of onset, in a subset of 100 hospitals participating in the Get With The Guidelines–Stroke quality improvement program. The number of fluctuations, direction, and the overall improvement or worsening was recorded based on reports from the patient, family, or paramedics. Baseline NIHSS on arrival and at 72 hours (or discharge if before) and final diagnosis and stroke subtype were collected. Outcomes at 90 days included the modified Rankin Scale, Barthel Index, Stroke Impact Scale 16, and European Quality of Life. Prehospital fluctuations were examined in relation to hospital NIHSS change (admission to 72 hours or discharge) and 90-day outcomes. Results: Among 1588 participants, prehospital fluctuations, consisting of improvement, worsening, or both were observed in 35.5%: 25.1% improved once, 5.3% worsened once, and 5.1% had more than 1 fluctuation. Those who improved were less likely and those who worsened were more likely to receive alteplase. Those who improved before hospital arrival had lower change in the hospital NIHSS than those who did not fluctuate. Better adjusted 90-day outcomes were noted in those with prehospital improvement compared to those without any fluctuations. Conclusions: Fluctuations in neurological symptoms and signs are common in the prehospital setting. Prehospital improvement was associated with better 90-day outcomes, controlling for admission NIHSS and alteplase treatment. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT 02072681.

Supplemental Digital Content is available in the text., Background and Purpose: The coronavirus disease 2019 (COVID-19) pandemic has created challenges in the delivery of acute stroke care. In this study, we analyze the characteristics, evaluation, treatment, and in-hospital outcomes of patients presenting with acute ischemic stroke (AIS) pre-COVID-19 and during COVID-19. Methods: Get With The Guidelines-Stroke is a national registry of adults with stroke in the United States. Using this registry, we identified patients with a diagnosis of AIS before (n=39 113; November 1, 2019–February 3, 2020) and after (n=41 971; February 4, 2020–June 29, 2020) the first reported case of COVID-19 in the registry. Characteristics, treatment patterns, quality metrics, and in-hospital outcomes were compared between the 2 groups. Results: Stroke presentations decreased by an average of 15.3% per week in the during COVID-19 time period when compared with similar months in 2019. Compared with patients with AIS in the pre-COVID-19 era, patients in the COVID-19 time period had similar rates of intravenous alteplase and endovascular therapy, and similar door to computed tomography, door to needle, and door to endovascular therapy times. In adjusted models, inpatient mortality was similar between those presenting with AIS pre-COVID-19 and during COVID-19 (4.8% versus 5.2%; odds ratio, 1.05 [95% CI, 0.97–1.13]). Conclusions: Among hospitals participating in Get With The Guidelines-Stroke, patients presenting with AIS during COVID-19 received, with few exceptions, similar quality care and experienced similar risk-adjusted outcomes when compared with patients with AIS presenting pre-COVID-19. These findings demonstrate that stroke care in the United States remains robust during the COVID-19 pandemic.

Background Emerging evidence links acute kidney injury (AKI) in patients with COVID‐19 with higher mortality and respiratory morbidity, but the relationship of AKI with cardiovascular disease outcomes has not been reported in this population. We sought to evaluate associations between chronic kidney disease (CKD), AKI, and mortality and cardiovascular outcomes in patients hospitalized with COVID‐19. Methods and Results In a large multicenter registry including 8574 patients with COVID‐19 from 88 US hospitals, data were collected on baseline characteristics and serial laboratory data during index hospitalization. Primary exposure variables were CKD (categorized as no CKD, CKD, and end‐stage kidney disease) and AKI (classified into no AKI or stages 1, 2, or 3 using a modification of the Kidney Disease Improving Global Outcomes guideline definition). The primary outcome was all‐cause mortality. The key secondary outcome was major adverse cardiac events, defined as cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, new‐onset nonfatal heart failure, and nonfatal cardiogenic shock. CKD and end‐stage kidney disease were not associated with mortality or major adverse cardiac events after multivariate adjustment. In contrast, AKI was significantly associated with mortality (stage 1 hazard ratio [HR], 1.72 [95% CI, 1.46–2.03]; stage 2 HR, 1.83 [95% CI, 1.52–2.20]; stage 3 HR, 1.69 [95% CI, 1.44–1.98]; versus no AKI) and major adverse cardiac events (stage 1 HR, 2.17 [95% CI, 1.74–2.71]; stage 2 HR, 2.70 [95% CI, 2.07–3.51]; stage 3 HR, 3.06 [95% CI, 2.52–3.72]; versus no AKI). Conclusions This large study demonstrates a significant association between AKI and all‐cause mortality and, for the first time, major adverse cardiovascular events in patients hospitalized with COVID‐19.

Background: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective is to describe multidimensional outcomes, identify predictors of worse outcomes and explore the effect of thrombolysis in this population. Methods: This prospective observational study included patients with ischemic stroke or TIA presenting with stroke symptoms and a baseline NIHSS 0-5 within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale (mRS) 0-1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16 (SIS-16) and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. Results: A total of 1765 participants were included from 100 Get With The Guidelines (GWTG)-Stroke participating hospitals (age 65 + 14, 42% women, final diagnosis ischemic stroke 90%, TIA 10%, 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, arm and leg weakness. Similar outcomes were noted for the alteplase-treated and the untreated groups. Alteplase treated patients were younger (64 + 13 vs. 67 + 1.4) with a higher NIHSS (2.9 + 1.4 vs. 1.7 + 1.4). After adjusting for age, sex, race-ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an effect on SIS-16 in the restricted sample of baseline NIHSS 3-5. Very few symptomatic hemorrhages were recorded (3/999). Conclusions: A large proportion of stroke patients presenting with a low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort but an indication of efficacy was noted in the NIHSS 3-5 subgroup.

Background: In response to the public health emergency created by the coronavirus disease 2019 (COVID-19) pandemic, American Heart Association volunteers and staff aimed to rapidly develop and launch a resource for the medical and research community to expedite scientific advancement through shared learning, quality improvement, and research. In Methods and Results: Participating hospitals are enrolling consecutive hospitalized patients with active COVID-19 disease, regardless of CVD status. This hospital quality improvement program will allow participating hospitals and health systems to evaluate patient-level data including mortality rates, intensive care unit bed days, and ventilator days from individual review of electronic medical records of sequential adult patients with active COVID-19 infection. Participating sites can leverage these data for onsite, rapid quality improvement, and benchmarking versus other institutions. After 9 weeks, >130 sites have enrolled in the program and >4000 records have been abstracted in the national dataset. Additionally, the aggregate dataset will be a valuable data resource for the medical research community. Conclusions: The AHA COVID-19 CVD Registry will support greater understanding of the impact of COVID-19 on cardiovascular disease and will inform best practices for evaluation and management of patients with COVID-19.

On April 1, 2020, the confirmed global burden of COVID-19 was more than 900,000 with 46,413 deaths Despite worldwide calls for social distancing and containment, the incidence of the disease continues to increase COVID-19 is a respiratory tract infection caused by the novel coronavirus (SARS-CoV2) Preliminary analyses from the Chinese Center for Disease Control and Prevention indicated an overall case fatality rate (CFR) of 2 3%;however the CFR was higher in older adults (14 8% in those 80+/- years) and 49% of all critical cases Those with preexisting conditions (cardiovascular disease (CVD), diabetes, chronic respiratory disease, hypertension, and cancer) also had higher CRFs In the United States, 116 million adults have hypertension, 26 million US adults have diabetes mellitus, 9% have preexisting CVD and may therefore be at greater risk of complications or adverse health outcomes from COVID-19 infection

Key Points Question What factors are associated with observed trends in the in-hospital mortality rates in the United States during the first 9 months of the COVID-19 pandemic? Findings In this cohort study of 20 736 patients, in-hospital mortality rates decreased in the US between March and November 2020, even after accounting for the changing mix in patient age, sex, comorbidities, and disease severity at the time of admission. Hospital and intensive care unit length of stay and use of mechanical ventilation decreased over time, whereas the use of glucocorticoids and remdesivir increased. Meaning Changes in age, sex, comorbidities, and disease severity among patients with COVID-19 do not fully explain the decrease in the in-hospital mortality rates observed during the first 9 months of the COVID-19 pandemic., Importance In-hospital mortality rates from COVID-19 are high but appear to be decreasing for selected locations in the United States. It is not known whether this is because of changes in the characteristics of patients being admitted. Objective To describe changing in-hospital mortality rates over time after accounting for individual patient characteristics. Design, Setting, and Participants This was a retrospective cohort study of 20 736 adults with a diagnosis of COVID-19 who were included in the US American Heart Association COVID-19 Cardiovascular Disease Registry and admitted to 107 acute care hospitals in 31 states from March through November 2020. A multiple mixed-effects logistic regression was then used to estimate the odds of in-hospital death adjusted for patient age, sex, body mass index, and medical history as well as vital signs, use of supplemental oxygen, presence of pulmonary infiltrates at admission, and hospital site. Main Outcomes and Measures In-hospital death adjusted for exposures for 4 periods in 2020. Results The registry included 20 736 patients hospitalized with COVID-19 from March through November 2020 (9524 women [45.9%]; mean [SD] age, 61.2 [17.9] years); 3271 patients (15.8%) died in the hospital. Mortality rates were 19.1% in March and April, 11.9% in May and June, 11.0% in July and August, and 10.8% in September through November. Compared with March and April, the adjusted odds ratios for in-hospital death were significantly lower in May and June (odds ratio, 0.66; 95% CI, 0.58-0.76; P, This cohort study of patients included in the US American Heart Association COVID-19 Cardiovascular Disease Registry evaluates whether any changes in the in-hospital COVID-19 mortality rates during the first 9 months of the pandemic are associated with individual characteristics of patients with COVID-19.

In the United States, 23.4 million adults have physician‐diagnosed diabetes mellitus (DM),1 81.6 million have prediabetes, and ≈18 000 people under age 20 years are diagnosed with type 1 DM each year.2 Approximately 90% to 95% of all adult DM cases are type 2.2 As such, data mentioned throughout will primarily comprise patients with type 2 DM. Patients with DM are 2 to 4 times more likely to die of cardiovascular disease (CVD) than patients without DM. The prevalence of patients living with DM and prediabetes continues to increase, putting these individuals at greater risk of having a heart attack or stroke. Often patients with DM have multiple other health problems and must also manage other cardiometabolic health risk factors such as obesity, hypertension, and high cholesterol. Because of the direct impact DM and related cardiometabolic disorders have on CVD, the American Heart Association (AHA) is building a multifaceted initiative to (1) unite the primary care, cardiology, endocrinology, and other specialty care provider communities in a comprehensive approach to caring for and treating patients with cardiometabolic conditions such as DM; (2) educate and empower people living with cardiometabolic disorders and DM to better self‐manage their condition(s) and improve their cardiovascular health. By expanding AHA's efforts to include initiatives and programs to reduce the prevalence and impact of cardiometabolic risk factors (such as prediabetes) and conditions (such as DM), the AHA will progress toward its mission of building healthier lives, free of cardiovascular diseases and stroke. To launch this new initiative, AHA held its first Cardiometabolic Health and Diabetes Summit on December 5, 2017, in Dallas, Texas. The objective was to identify and prioritize opportunities to improve cardiometabolic health and DM care in the United States (Figure 1). Open in a separate window Figure 1 American Heart Association Summit key opportunities.

Each chapter listed in the Table of Contents (see next page) is a hyperlink to that chapter. The reader clicks the chapter name to access that chapter. Each chapter listed here is a hyperlink. Click on the chapter name to be taken to that chapter. Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together in a single document the most up-to-date statistics related to heart disease, stroke, and the cardiovascular risk factors listed in the AHA’s My Life Check - Life’s Simple 7 (Figure1), which include core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure [BP], and glucose control) that contribute to cardiovascular health. The Statistical Update represents …

Multiple randomized controlled trials (RCTs) have assessed the effects of supplementation with eicosapentaenoic acid plus docosahexaenoic acid (omega-3 polyunsaturated fatty acids, commonly called fish oils) on the occurrence of clinical cardiovascular diseases. Although the effects of supplementation for the primary prevention of clinical cardiovascular events in the general population have not been examined, RCTs have assessed the role of supplementation in secondary prevention among patients with diabetes mellitus and prediabetes, patients at high risk of cardiovascular disease, and those with prevalent coronary heart disease. In this scientific advisory, we take a clinical approach and focus on common indications for omega-3 polyunsaturated fatty acid supplements related to the prevention of clinical cardiovascular events. We limited the scope of our review to large RCTs of supplementation with major clinical cardiovascular disease end points; meta-analyses were considered secondarily. We discuss the features of available RCTs and provide the rationale for our recommendations. We then use existing American Heart Association criteria to assess the strength of the recommendation and the level of evidence. On the basis of our review of the cumulative evidence from RCTs designed to assess the effect of omega-3 polyunsaturated fatty acid supplementation on clinical cardiovascular events, we update prior recommendations for patients with prevalent coronary heart disease, and we offer recommendations, when data are available, for patients with other clinical indications, including patients with diabetes mellitus and prediabetes and those with high risk of cardiovascular disease, stroke, heart failure, and atrial fibrillation.

This article is one of a series of 4 that report on a task of the NanoRelease Food Additive project of the International Life Science Institute Center for Risk Science Innovation and Application to identify, evaluate, and develop methods that are needed to confidently detect, characterize, and quantify intentionally produced engineered nanomaterials (ENMs) released from food along the alimentary tract. This particular article focuses on the problem of detecting and characterizing ENMs in the various compartments of the alimentary tract after they have been ingested from dietary sources. An in depth analysis of the literature related to oral toxicity of ENMs is presented, paying particular attention to analytical methodology and sample preparation. The review includes a discussion of model systems that can be used to study oral uptake of ENMs in the absence of human toxicological data or other live-animal studies. The strengths and weaknesses of various analytical and sample preparation techniques are discussed. The article concludes with a summary of findings and a discussion of potential knowledge gaps and targets for method development in this area.

Scientists participating in 2 multistakeholder meetings in 2011 and in other events have identified a number of ways in which the methods the U.S. Food and Drug Administration (FDA) uses to assess the safety of chemicals in human food should be improved and updated. We evaluated whether FDA's current methods, including its decision-making process, are outdated, as alleged by its critics. We examined a 1982 report by the Select Committee on GRAS Substances (SCOGS) that included suggestions to enhance food additive safety. FDA established SCOGS to review the safety of "generally recognized as safe" (GRAS) substances in response to a directive by President Nixon. When evaluating FDA's response to SCOGS' suggestions, we found that many remain unresolved and relevant today. Our analysis demonstrates that in many cases FDA has not kept pace with scientific developments. Although difficult to pinpoint, we concluded that this situation became more significant after 1997, when FDA launched the voluntary GRAS notification program aimed at enticing manufacturers to inform the agency of their own safety decisions. Looking forward, we recommend that the agency convene an unbiased and independent expert workgroup to conduct a comprehensive review of FDA's science and decision making and develop a path to modernize food additives safety assessment. Areas of concern include toxicology test guidelines, tools used to predict health outcomes, conflict of interest in manufacturers' decisions, lack of a reassessment strategy, and lack of a definition of harm.

Food additives and substances considered “generally recognized as safe” must not be allowed in food unless there is a reasonable certainty in the minds of competent scientists that the substance is not harmful under the intended conditions of use. Scientists determine safety by ensuring that the expected exposure is less than the acceptable daily intake. The U.S. Food and Drug Administration (FDA) provides guidance documents to assist safety assessors in this analysis. A November 2011 workshop sponsored by The Pew Charitable Trusts, the Institute of Food Technologists, and the journal Nature reviewed the agency's exposure assessment approaches. More than 70 experts from government (including FDA), industry, academia, and public interest organizations examined the principles underlying dietary exposure assessments for substances added to human food, and responded to questions about current methods. FDA's approach was seen as serving the agency reasonably well, but participants identified opportunities for improvement. Although reaching a consensus was not a goal, general agreements emerged that FDA should develop a science-based framework to prioritize and reassess prior safety decisions, and conduct more extensive postmarket monitoring. Participants discussed the possibility of harmonizing different approaches to assess dietary exposure. They generally agreed that collaboration, communication, and exchanging scientific information between agencies and stakeholders would help assessors use the most current information to make better decisions. Participants identified data gaps and opportunities to fill the gaps using new tools and technologies. Participants generally agreed on the need to consider all dietary sources in a cumulative dietary exposure assessment.

Science and expert judgment are the foundation for safety assessments of chemicals added to food to ensure their use is safe. Hazard characterization is the first step in a safety assessment. Advances in science and technology pose challenges to the regulatory system and raise questions about whether the current hazard identification and characterization process is able to systematically and transparently encompass such advances while remaining defensible. An April 2011 workshop sponsored by The Pew Charitable Trusts, the Institute of Food Technologists, and the journal Nature brought together over 80 experts in science and food policy from government, industry, academia, and public interest organizations to examine the principles underlying the development and use of scientific evidence needed for chemical hazard characterization. Participants discussed challenges of identifying adverse health effects, advances in science, uses of new screening technologies and human biomonitoring data, updating of study designs, and development and review of toxicity test guidelines. Brainstorming sessions allowed participants to propose alternatives to enhance FDA's evaluation of science for safety assessment. Although there was no intention to reach a consensus, several themes emerged including the need for clear procedures to develop validated toxicity tests; importance of regularly updating guidance documents relied upon by regulators and industry; benefits of transparency and public access to information; potential for greater interagency collaboration; opportunities to improve hypothesis-based research to make it more useful to regulatory decision making; and importance of staying abreast of scientific developments to ensure that safety assessments are made using sensitive and relevant methods.

The Food Additives Amendment of 1958 is the foundation for the U.S. food additive regulatory program, which oversees most substances added to food. This article is a comprehensive review of the program, including original analysis of pre- and postmarket safety standards for various categories and subcategories of substances and their uses; assigning the more than 10000 substances currently allowed in human food to those categories; and analyzing the U.S. Food and Drug Administration's (FDA) review of more than 1900 petitions and notifications received from 1990 to 2010. Overall, federal agencies made approximately 40% of the 6000 safety decisions allowing substances in human food. These decisions allowed an estimated 66% of the substances currently believed to be used in food. Manufacturers and a trade association made the remaining decisions without FDA review by concluding that the substances were generally recognized as safe (GRAS). Robust premarket safety decisions are critical since FDA has limited resources to monitor potentially significant scientific developments and changing uses of a substance after it enters commerce and only has access to published data or data submitted to it. In the late 1990s, FDA moved from promulgating rules for its decisions for food contact and GRAS substances to reviewing manufacturer safety decisions and posting the results of the review on the agency's website. This shift appears to have encouraged manufacturers to submit their decisions to FDA for review but has limited public opportunity to provide input.

Importance Food and Drug Administration (FDA) guidance allows food manufacturers to determine whether additives to food are “generally recognized as safe” (GRAS). Manufacturers are not required to notify the FDA of a GRAS determination, although in some instances they notify the agency. The individuals that companies select to make these determinations may have financial conflicts of interest. Objective To determine the extent to which individuals selected by manufacturers to make GRAS determinations have conflicts of interest between their obligations to ensure that the use of the additive is safe and their financial relationships to the company. Design Using conflict of interest criteria developed by a committee of the Institute of Medicine, we analyzed 451 GRAS notifications that were voluntarily submitted to the FDA between 1997 and 2012. Main Outcomes and Measures Number of GRAS notices submitted to the FDA; frequency of various types of relationships between decision maker and additive manufacturer; frequency of participation on GRAS panels by individuals; and number of GRAS safety determinations identified by the FDA that were not submitted to the agency. Results For the 451 GRAS notifications, 22.4% of the safety assessments were made by an employee of an additive manufacturer, 13.3% by an employee of a consulting firm selected by the manufacturer, and 64.3% by an expert panel selected by either a consulting firm or the manufacturer. A standing expert panel selected by a third party made none of these safety assessments. The 290 panels that made GRAS determinations had an average of 3.5 members, with a maximum of 7. Ten individuals served on 27 or more panels; 1 individual served on 128 panels (44.1%). At least 1 of the 10 individuals with the most frequent service was a member of 225 panels (77.6%). Conclusions and Relevance Between 1997 and 2012, financial conflicts of interest were ubiquitous in determinations that an additive to food was GRAS. The lack of independent review in GRAS determinations raises concerns about the integrity of the process and whether it ensures the safety of the food supply, particularly in instances where the manufacturer does not notify the FDA of the determination. The FDA should address these concerns.