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Objectives/Goals: People with insulin-treated diabetes face hypoglycemia risk due to imperfect insulin replacement and impaired counterregulation. We identified the dopamine antagonist, metoclopramide, as a potential treatment. Hypothesis: Treatment with metoclopramide will prevent the development of impaired counterregulatory response to hypoglycemia. Methods/Study Population: In a pre-clinical model, diabetes was induced in 10-week-old Sprague-Dawley rats with streptozotocin (STZ, 65 mg/kg IP). Rats were divided into three groups: 1) diabetic controls (STZ+RS, n = 6), 2) recurrent hypoglycemia (STZ+RH, n = 7), and 3) recurrent hypoglycemia + metoclopramide (STZ+RH+MET, 3 mg/kg IP, n = 7). After 3 days, all rats underwent a hyperinsulinemic (50 mU/kg/min) and hypoglycemic (~45 mg/dl) clamp. In the clinical trial, adults with Type 1 diabetes (age 20–60, ≥5 years duration) were enrolled in a phase II, double-blinded, placebo-controlled trial. Awareness status was assessed via Gold score, and subjects maintained drug regimens and underwent two hyperinsulinemic-hypoglycemic clamps (where blood glucose was lowered to 100, 65, 55, and 45 mg/dl) to assess counterregulation. Results/Anticipated Results: In the pre-clinical model, glucose infusion rates (GIR) to maintain hypoglycemia were higher in STZ+RH (27±0.9 mg/kg/min) than STZ+RS (19±0.8 mg/kg/min, p Discussion/Significance of Impact: Metoclopramide improves glucoregulatory, sympathoadrenal, and counterregulatory responses to hypoglycemia in pre-clinical models, suggesting dopaminergic regulation. While clinical data are still blinded, increased epinephrine and growth hormone responses suggest treatment may preserve or restore counterregulation.
To understand caregivers’ perceptions about their children’s mealtime social experiences at school and how they believe these social experiences impact their children’s consumption of meals at school (both meals brought from home and school meals).
Design:
Qualitative data were originally collected as part of a larger mixed methods study using an embedded-QUAN dominant research design.
Setting:
Semi-structured interviews were conducted with United States (U.S.) caregivers over ZoomTM in English and Spanish during the 2021–2022 school year. The interview guide contained 14 questions on caregivers’ perceptions about their children’s experiences with school meals.
Participants:
Caregivers of students in elementary, middle and high schools in rural, suburban and urban communities in California (n 46) and Maine (n 20) were interviewed. Most (60·6 %) were caregivers of children who were eligible for free or reduced-price meals.
Results:
Caregivers reported that an important benefit of eating meals at school is their child’s opportunity to socialise with their peers. Caregivers also stated that their child’s favourite aspect of school lunch is socialising with friends. However, some caregivers reported the cafeteria environment caused their children to feel anxious and not eat. Other caregivers reported that their children sometimes skipped lunch and chose to socialise with friends rather than wait in long lunch lines.
Conclusions:
Socialising during school meals is important to both caregivers and students. Policies such as increasing lunch period lengths and holding recess before lunch have been found to promote school meal consumption and could reinforce the positive social aspects of mealtime for students.
Next generation high-power laser facilities are expected to generate hundreds-of-MeV proton beams and operate at multi-Hz repetition rates, presenting opportunities for medical, industrial and scientific applications requiring bright pulses of energetic ions. Characterizing the spectro-spatial profile of these ions at high repetition rates in the harsh radiation environments created by laser–plasma interactions remains challenging but is paramount for further source development. To address this, we present a compact scintillating fiber imaging spectrometer based on the tomographic reconstruction of proton energy deposition in a layered fiber array. Modeling indicates that spatial resolution of approximately 1 mm and energy resolution of less than 10% at proton energies of more than 20 MeV are readily achievable with existing 100 μm diameter fibers. Measurements with a prototype beam-profile monitor using 500 μm fibers demonstrate active readouts with invulnerability to electromagnetic pulses, and less than 100 Gy sensitivity. The performance of the full instrument concept is explored with Monte Carlo simulations, accurately reconstructing a proton beam with a multiple-component spectro-spatial profile.
Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.
Design:
We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).
Results:
At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.
Conclusions:
Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
The objective of our study was to determine the prevalence of anaemia among 14–19 years school going girls, risk factors for it and profile of micronutrient status among rural girls from western state of India.
Design:
Using a cross-sectional design, we obtained information on socio-demography, menstruation, dietary habits, knowledge and daily consumption of the government recommended iron and folic acid (IFA) tablets, and anthropometry. Blood was collected to assess Hb, red blood cell indices, serumFe, folate and vitamin B12 levels.
Settings:
Nagpur district, Maharashtra, India.
Participants:
A total of 221 girls aged 14–19 years studying in twenty-four government institutes included.
Results:
57 % girls were anaemic, 84 % had deficiency of one or more micronutrients and 60 % were malnourished based on body mass index (BMI). The prevalence of Fe, vitamin B12 and folate deficiency was 37·7 %, 69·8 % and 1·4 %, respectively. Among anaemic girls, Fe and vitamin B12 deficiency was observed in 45·5 % and 67·5 %, respectively, v. among non-anaemic girls it was 27 % and 73 %, respectively. Fe deficiency was a predictor of anaemia and its severity. Girls residing in non-nuclear family were more likely to have anaemia. The consumption of daily non-vegetarian food and green leafy vegetables was 3 % and 3·6 %, respectively. Only 9 % consumed IFA tablets in the past 2 weeks.
Conclusions:
Anaemia is common in adolescent girls, particularly associated with Fe and vitamin B12 deficiency. There is need to reconsider the approach to prevention of anaemia in adolescent girls, particularly before they become pregnant.
Behaviour Change Communication (BCC) intervention programmes often lack documentation of successful processes. This manuscript aims to describe the development of Program Impact Pathway (PIP) using Theory of Change (ToC) approach for a mHealth BCC intervention titled ‘Mobile Solutions Aiding Knowledge for Health Improvement (M-SAKHI)’ aimed at reducing stunting in infants at 18 months of age.
Design:
The PIP was developed using ToC to design the intervention and plan its implementation. Literature review and data from previous pilots helped to identify health service gaps that needed to be addressed by the PIP of this intervention.
Setting:
M-SAKHI was implemented in 244 villages under governance of forty primary health centres of Nagpur and Bhandara districts of eastern Maharashtra in central India.
Participants:
The study investigators and the public health stakeholders participated in developing the PIP. M-SAKHI evaluation study recruited 2501 pregnant women who were followed up through delivery until their infants were 18 months old.
Results:
The PIP was developed, and it identified the following pathways for the final impact: (1) improving maternal and infant nutrition, (2) early recognition of maternal and infant danger signs, (3) improving access and utilisation to healthcare services, (4) improving hygiene, sanitation and immunisation practices, and (5) improving implementation and service delivery of community health workers through their training, monitoring and supervision in real time.
Conclusion:
This paper will illustrate the significance of development of PIP for M-SAKHI. It can aid other community-based programmes to design their PIP for nutrition-based BCC interventions.
Chronic pain patients often contend with insomnia symptoms, creating a reciprocal relationship that adds complexity to their condition. Evaluating interventions targeting insomnia in this population becomes paramount, given the intertwined nature of pain and sleep disturbances.
Objectives
This retrospective pretest design aimed to assess the efficacy of an Internet-delivered sound healing intervention in reducing insomnia severity and addressing sleep- and pain-related parameters among individuals with chronic pain.
Methods
Conducted as a community-based project, Tuning for Health provided support to individuals grappling with long-term illnesses. The intervention involved the virtual delivery of a specially crafted sound track using tuning forks over a 6-week period, supervised by an experienced therapist and administered weekly for an hour. Participants were instructed to play the track daily at a time convenient for them. A total of 68 participants (mean age 59.3 years) completed the intervention. Outcome measures, including the Insomnia Severity Index (ISI), a sleep diary, and assessments for anxiety, depression, and pain-related parameters, were collected at the end of the 6-week intervention and repeated after a 6-month follow-up. Negative effects were monitored and reported.
Results
Significant immediate interaction effects (time by treatment) were observed for the pain severity, ISI and various sleep parameters, such as sleep efficiency, sleep onset latency, early morning awakenings, and wake time after sleep onset. A time effect for anxiety and depression was noted at the 6-month follow-up. The group exhibited highly significant improvements in pain-related parameters. At the 6-month follow-up, sustained enhancements in sleep parameters and mental health were reported, with no reported side effects.
Conclusions
These unique results suggest the potential efficacy of sound healing in alleviating chronic pain and associated insomnia. Further research with a larger sample size is warranted to validate these findings. Combining sound healing with other treatments may offer enhanced outcomes for individuals dealing with both chronic pain and comorbid insomnia. This study lays the groundwork for future investigations into the promising intersection of sound healing, chronic pain management, and sleep improvement.
The overuse of antibiotics in medicine has led to concerns over management of wound infections where antibiotic-resistant bacteria are involved. Wound infections exhibit both acquired and biofilm-associated antibiotic resistance; innovative non-antibiotic therapeutic and preventive treatments are needed to limit emergence of conventional antimicrobial resistance and to address biofilm-associated resistance. Toward this goal, natural antibacterial clays have been identified that are effective at killing drug-resistant human pathogens in planktonic and biofilm states, in vitro. To move toward clinical testing of antibacterial clays, the present study was conducted to evaluate the topical application of a natural antibacterial clay to wounds in mice experimentally infected with methicillin-resistant Staphylococcus aureus (MRSA). Five preliminary animal trials were conducted to test various methods of applying hydrated antibacterial clay to infected wounds. None of the experiments yielded significantly reduced MRSA infection in vivo, compared to controls. Several hypotheses were tested to explore the diminished clay antibacterial activity in vivo including: (1) pH and Eh of mineral-bacterial suspensions may differ in wound fluids compared to growth media; (2) antibacterial reactants may complex with components of the wound; (3) hydrated clays may dry out in the wound; and (4) limited dissolved oxygen may reduce Fenton reactions. Ancillary in vitro tests were performed to explore these hypotheses. Results indicate that the clay application to wounds may require enhanced oxidation and possibly a longer treatment regimen. The experimental results foster understanding of the natural clay–bacterial interactions in wounds and may improve designs for medicinal applications.
Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.
Participants and Methods:
The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and
relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).
Results:
APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).
Conclusions:
Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.
We established a surveillance program to evaluate persistence of C. auris colonization among hospitalized patients. Overall, 17 patients (34%) had ≥1 negative result followed by a positive test, and 7 (41%) of these patients had ≥2 consecutive negative tests.
The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT’s are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment.
Assess turnaround time (TAT) and cost-benefit of on-site C. auris screening and its impact on length of stay (LOS) and costs compared to reference laboratories.
Design:
Before-and-after retrospective cohort study.
Setting:
Large-tertiary medical center.
Methods:
We validated an on-site polymerase chain reaction-based testing platform for C. auris and retrospectively reviewed hospitalized adults who screened negative before and after platform implementation. We constructed multivariable models to assess the association of screening negative with hospital LOS/cost in the pre and postimplementation periods. We adjusted for confounders such as demographics and indwelling device use, and compared TATs for all samples tested.
Results:
The sensitivity and specificity of the testing platform were 100% and 98.11%, respectively, compared to send-out testing. The clinical cohort included 287 adults in the pre and 1,266 postimplementation period. The TAT was reduced by more than 2 days (3 (interquartile range (IQR): 2.0, 7.0) vs 0.42 (IQR: 0.24, 0.81), p < 0.001). Median LOS was significantly lower in the postimplementation period; however, this was no longer evident after adjustment. In relation to total cost, the time period had an effect of $6,965 (95% CI: −$481, $14,412); p = 0.067) on reducing the cost. The median adjusted total cost per patient was $7,045 (IQR: $3,805, $13,924) less in the post vs the preimplementation period.
Conclusions:
Our assessment did not find a statistically significant change in LOS, nevertheless, on-site testing was not cost-prohibitive for the institution. The value of on-site testing may be supported if an institutional C. auris reduction strategy emphasizes faster TATs.
OBJECTIVES/GOALS: This study examined patient perceptions on the benefits, barriers, and facilitators of conventional and complementary/behavioral pain strategies that can be offered in the ED setting including physical therapy, mindfulness, acupuncture, and yoga. METHODS/STUDY POPULATION: We conducted and recorded semi-structured interviews with 30 patients who presented to the ED with musculoskeletal pain. Interviews focused on patients’ perceptions of NP pain treatments, barriers/facilitators to utilization, and recommendations that would promote engagement. A hierarchical coding system was developed and refined using the interview guide, the Theory of Planned Behavior, and preliminary review of the transcripts. The iterative process of developing the coding system allowed us to identify preliminary themes. RESULTS/ANTICIPATED RESULTS: Patients believe education on pain and the mind-body connection would give a sense of pain control. Likely barriers to engaging at the ED include lights, noise, interruptions, and uncertainty of their medical status. Post-discharge NP treatment barriers are financial and logistical. Engagement can be facilitated by a desire to avoid opioids, familiarity with meditation practices, and consistent positive communication with the health care team. Patients desire evidence on effectiveness, including testimonials, and suggested NP techniques should be introduced early, with written materials used for post-discharge referral. Patients prefer in-person treatment but would appreciate a virtual option. The initial session should occur in-person to build trust and facilitate virtual session engagement. DISCUSSION/SIGNIFICANCE: Patients are willing to engage in nonpharmacological pain treatment, however the unpredictable ED environment, uncertainty of their medical status, and financial and time constraints are significant barriers.
Screening individuals admitted to the hospital for Clostridioides difficile presents opportunities to limit transmission and hospital-onset C. difficile infection (HO-CDI). However, detection from rectal swabs is resource intensive. In contrast, machine learning (ML) models may accurately assess patient risk without significant resource usage. In this study, we compared the effectiveness of swab surveillance to daily risk estimates produced by an ML model to identify patients who will likely develop HO-CDI in the intensive care unit (ICU) setting.
Design:
A prospective cohort study was conducted with patient carriage of toxigenic C. difficile identified by rectal swabs analyzed by anaerobic culture and polymerase chain reaction (PCR). A previously validated ML model using electronic health record data generated daily risk of HO-CDI for every patient. Swab results and risk predictions were compared to the eventual HO-CDI status.
Patients:
Adult inpatient admissions taking place in University of Michigan Hospitals’ medical and surgical intensive care units and oncology wards between June 6th and October 8th, 2020.
Results:
In total, 2,979 admissions, representing 2,044 patients, were observed over the course of the study period, with 39 admissions developing HO-CDIs. Swab surveillance identified 9 true-positive and 87 false-positive HO-CDIs. The ML model identified 9 true-positive and 226 false-positive HO-CDIs; 8 of the true-positives identified by the model differed from those identified by the swab surveillance.
Conclusion:
With limited resources, an ML model identified the same number of HO-CDI admissions as swab-based surveillance, though it generated more false-positives. The patients identified by the ML model were not yet colonized with C. difficile. Additionally, the ML model identifies at-risk admissions before disease onset, providing opportunities for prevention.
We aimed to identify factors independently associated with the need for inotropic support for low cardiac output or haemodynamic instability after pulmonary artery banding surgery for CHD.
Methods:
We performed a retrospective chart review of all neonates and infants who underwent pulmonary banding between January 2016 and June 2019 at our institution. Bivariate and multivariable analyses were performed to identify factors independently associated with the use of post-operative inotropic support, defined as the initiation of inotropic infusion(s) for depressed myocardial function, hypotension, or compromised perfusion within 24 hours of pulmonary artery banding.
Results:
We reviewed 61 patients. Median age at surgery was 10 days (25%,75%:7,30). Cardiac anatomy was biventricular in 38 patients (62%), hypoplastic right ventricle in 14 patients (23%), and hypoplastic left ventricle in 9 patients (15%). Inotropic support was implemented in 30 patients (49%). Baseline characteristics of patients who received inotropic support, including ventricular anatomy and pre-operative ventricular function, were not statistically different from the rest of the cohort. Patients who received inotropic support, however, were exposed to larger cumulative doses of ketamine intraoperatively – median 4.0 mg/kg (25%,75%:2.8,5.9) versus 1.8 mg/kg (25%,75%:0.9,4.5), p < 0.001. In a multivariable model, cumulative ketamine dose greater than 2.5mg/kg was associated with post-operative inotropic support (odds ratio 5.5; 95% confidence interval: 1.7,17.8), independent of total surgery time.
Conclusions:
Inotropic support was administered in approximately half of patients who underwent pulmonary artery banding and more commonly occurred in patients who received higher cumulative doses of ketamine intraoperatively, independent of the duration of surgery.
Children with single-sided deafness often receive inconsistent clinical recommendations because there is currently no clear best practice in paediatric single-sided deafness. This systematic review of the literature aimed to compare commonly used treatments and attempted to support the use of a particular treatment modality.
Method
This was a comprehensive literature review from 1 January 2000 to 22 February 2022; the study compared the outcomes of bone conduction devices and cochlear implantation in paediatric patients with single-sided deafness.
Results
Fifteen studies consisting of 202 patients were examined. Variables including speech reception in quiet and noise, as well as quality of life measures were compared. Both cochlear implantation and bone-anchored hearing aids demonstrated benefits in sound perception. Quality of life measures improved with both modalities.
Conclusion
Although both bone-anchored hearing aids and cochlear implantation appear to provide significant improvements, additional research with more direct comparisons is needed to provide more decisive results.
From 2016–2019, dry bulb onions were the suspected cause of three multistate outbreaks in the United States. We investigated a large multistate outbreak of Salmonella Newport infections that caused illnesses in both the United States and Canada in 2020. Epidemiologic, laboratory and traceback investigations were conducted to determine the source of the infections, and data were shared among U.S. and Canadian public health officials. We identified 1127 U.S. illnesses from 48 states with illness onset dates ranging from 19 June to 11 September 2020. Sixty-six per cent of ill people reported consuming red onions in the week before illness onset. Thirty-five illness sub-clusters were identified during the investigation and seventy-four per cent of sub-clusters served red onions to customers during the exposure period. Traceback for the source of onions in illness sub-clusters identified a common onion grower in Bakersfield, CA as the source of red onions, and onions were recalled at this time. Although other strains of Salmonella Newport were identified in environmental samples collected at the Bakersfield, CA grower, extensive environmental and product testing did not yield the outbreak strain. This was the third largest U.S. foodborne Salmonella outbreak in the last 30 years. It is the first U.S. multistate outbreak with a confirmed link to dry bulb onions, and it was nearly 10-fold larger than prior outbreaks with a suspected link to onions. This outbreak is notable for its size and scope, as well as the international data sharing that led to implication of red onions as the primary cause of the outbreak. Although an environmental assessment at the grower identified several factors that likely contributed to the outbreak, no main reason was identified. The expedient identification of the outbreak vehicle and response of multiple public health agencies allowed for recall and removal of product from the marketplace, and rapid messaging to both the public and industry on actions to protect consumers; these features contributed to a decrease in cases and expeditious conclusion of the outbreak.