A pathway linking pulse pressure to dementia in adults with Down syndrome.

Adults with Down syndrome are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease and is linked to a diagnosis of dementia in adults with Down syndrome via structural imaging markers of cerebrovascular disease and atrophy. The study included participants with Down syndrome from the Alzheimer's Disease - Down Syndrome study (n = 195, age = 50.6 ± 7.2 years, 44% women, 18% diagnosed with dementia). Higher pulse pressure was associated with greater global, parietal and occipital white matter hyperintensity volume but not with enlarged perivascular spaces, microbleeds or infarcts. Using a structural equation model, we found that pulse pressure was associated with greater white matter hyperintensity volume, which in turn was related to increased neurodegeneration, and subsequent dementia diagnosis. Pulse pressure is an important determinant of brain health and clinical outcomes in individuals with Down syndrome despite the low likelihood of frank hypertension.

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults.

Obstructive sleep apnea (OSA) is common in older adults and is associated with medial temporal lobe (MTL) degeneration and memory decline in aging and Alzheimer's disease (AD). However, the underlying mechanisms linking OSA to MTL degeneration and impaired memory remains unclear. By combining magnetic resonance imaging (MRI) assessments of cerebrovascular pathology and MTL structure with clinical polysomnography and assessment of overnight emotional memory retention in older adults at risk for AD, cerebrovascular pathology in fronto-parietal brain regions was shown to statistically mediate the relationship between OSA-related hypoxemia, particularly during rapid eye movement (REM) sleep, and entorhinal cortical thickness. Reduced entorhinal cortical thickness was, in turn, associated with impaired overnight retention in mnemonic discrimination ability across emotional valences for high similarity lures. These findings identify cerebrovascular pathology as a contributing mechanism linking hypoxemia to MTL degeneration and impaired sleep-dependent memory in older adults.

Risk of Cervical Abnormalities for Women With Multiple Sclerosis Treated With Moderate-Efficacy and High-Efficacy Disease-Modifying Therapies.

BACKGROUND AND OBJECTIVES: The impact of immunomodulatory therapies on the risk of cervical pre-cancer and invasive cancer development is important for the health and safety of women with multiple sclerosis (wwMS). We investigate the risk of cervical abnormalities in wwMS treated with disease-modifying therapies (DMTs). METHODS: This is a multicenter cohort study with data collected from 1998 to 2019 in Victoria, Australia. Data linkage was performed using matching records from the MSBase Registry, the National Human Papillomavirus (HPV) Vaccination Program Register, and the Victorian Cervical Cytology Register. The primary outcome was the detection of any type of cervical abnormality as determined by cytology or histology. Survival methods were used to assess the time to cervical abnormality detection on cervical screening tests (CSTs). Crude and adjusted Cox proportional hazards models were used to determine time to and magnitude of association of DMTs with the risk of cervical abnormality. In a sensitivity analysis, we constructed standardized survival curves averaged over the same set of covariates to determine the commensurate population-average (marginal) causal effects. RESULTS: We included 248 wwMS. The incidence of abnormal CSTs was lower (p < 0.001) for women not exposed to moderate-high-efficacy therapy (10.2 per 1,000 patient-years [95% confidence interval (CI) 5.5-14.9]), compared with those exposed (36.6 per 1,000 patient-years [95% CI 21.7-51.6]). Exposure to higher efficacy treatment was associated with a 3.79-fold increased hazard (95% CI 2.02-7.08, p < 0.001) of developing a cervical abnormality relative to those not exposed. When adjusted for vaccination status, smoking, hormonal contraceptive use, and socioeconomic status, the risk remained elevated at 3.79 (95% CI 1.99-7.21, p < 0.001). Marginal hazard ratios declined over time, ranging from 3.90 (95% CI 2.09-7.27) at 20 years of age to 2.06 (95% CI 1.14-3.73) at 70 years of age. DISCUSSION: A greater than three-and-a-half-fold increased risk of cervical abnormalities was found after exposure to moderate-high-efficacy DMTs. This risk persisted despite adjusting for HPV vaccination status, hormonal contraception use, smoking, and socioeconomic status. If confirmed in future studies, we would advocate for wwMS exposed to moderate-high-efficacy DMTs to be treated in line with immune-deficient paradigm in cervical screening and HPV vaccination programs. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that highly active MS therapy compared with less active therapy increases the risk of developing cervical abnormalities among women with MS.

Formal Ethics Consultation in Extracorporeal Membrane Oxygenation Patients: A Single-Center Retrospective Cohort of a Quaternary Pediatric Hospital.

OBJECTIVE: To examine characteristics associated with formal ethics consultation (EC) referral in pediatric extracorporeal membrane oxygenation (ECMO) cases, and document ethical issues presented. DESIGN: Retrospective cohort study using mixed methods. SETTING: Single-center quaternary pediatric hospital. PATIENTS: Patients supported on ECMO (January 2012 to December 2021). INTERVENTIONS: We compared clinical variables among ECMO patients according to the presence of EC. We defined optimal cutoffs for EC based on run duration, ICU length of stay (LOS), and sum of procedures or complications. To identify independent explanatory variables for EC, we used a forward stepwise selection multivariable logistic regression model. EC records were thematically characterized into ethical issues. MEASUREMENTS AND MAIN RESULTS: Of 601 ECMO patients and 225 patients with EC in 10 years, 27 ECMO patients received EC (4.5% of ECMO patients, 12% of all ECs). On univariate analysis, use of EC vs. not was associated with multiple ECMO runs, more complications/procedures, longer ICU LOS and ECMO duration, cardiac admissions, decannulation outcome, and higher mortality. Cutoffs for EC were ICU LOS >52 days, run duration >160 hours, and >6 complications/procedures. Independent associations with EC included these three cutoffs and older age. The model showed good discrimination (area under the curve 0.88 [0.83, 0.93]) and fit. The most common primary ethical issues were related to end-of-life, ECMO discontinuation, and treatment decision-making. Moral distress was cited in 22 of 27 cases (82%). CONCLUSION: EC was used in 4.5% of our pediatric ECMO cases, with most ethical issues related to end-of-life care or ECMO discontinuation. Older age, longer ICU LOS, prolonged runs, and multiple procedures/complications were associated with greater odds for EC requests. These data highlight our single-center experience of ECMO-associated ethical dilemmas. Historical referral patterns may guide a supported decision-making framework. Future work will need to include quality improvement projects for timely EC, with evaluation of impacts on relevant endpoints.

Results From the POINT Pragmatic Randomized Trial: An Emergency Department-Based Peer Support Specialist Intervention to Increase Opioid Use Disorder Treatment Linkage and Reduce Recurrent Overdose.

BACKGROUND: People with opioid use disorder (OUD) frequently present at the emergency department (ED), a potentially critical point for intervention and treatment linkage. Peer recovery support specialist (PRSS) interventions have expanded in US-based EDs, although evidence supporting such interventions has not been firmly established. METHODS: Researchers conducted a pragmatic trial of POINT (Project Planned Outreach, Intervention, Naloxone, and Treatment), an ED-initiated intervention for harm reduction and recovery coaching/treatment linkage in 2 Indiana EDs. Cluster randomization allocated patients to the POINT intervention (n = 157) versus a control condition (n = 86). Participants completed a structured interview, and all outcomes were assessed using administrative data from an extensive state health exchange and state systems. Target patients (n = 243) presented to the ED for a possible opioid-related reason. The primary outcome was overdose-related ED re-presentation. Key secondary outcomes included OUD medication treatment linkage, duration of medication in days, all-cause ED re-presentation, all-cause inpatient re-presentation, and Medicaid enrollment. All outcomes were assessed at 3-, 6-, and 12-months post-enrollment. Ad hoc analyses were performed to assess treatment motivation and readiness. RESULTS: POINT and standard care participants did not differ significantly on any outcomes measured. Participants who presented to the ED for overdose had significantly lower scores (3.5 vs 4.2, P < .01) regarding readiness to begin treatment compared to those presenting for other opioid-related issues. CONCLUSIONS: This is the first randomized trial investigating overdose outcomes for an ED peer recovery support specialist intervention. Though underpowered, results suggest no benefit of PRSS services over standard care. Given the scope of PRSS, future work in this area should assess more recovery- and harm reduction-oriented outcomes, as well as the potential benefits of integrating PRSS within multimodal ED-based interventions for OUD.

Fentanyl Exposure and Detection Strategies Utilized by Clinical Trial Participants Seeking Linkage to Opioid Use Disorder Treatment at a Syringe Service Program.

INTRODUCTION: The USA continues to face a fentanyl-driven overdose epidemic. Prior research has demonstrated users of illicit opioids are concerned about fentanyl exposure and overdose, but the strategies they report using to detect fentanyl's presence lack empirical support. This study compares self-report and biologically detected fentanyl use and investigates overdose risk and risk reduction behaviors among a sample of high-risk people who use opioids. METHODS: Structured enrollment interviews conducted as part of a larger clinical trial assessed self-reported fentanyl exposure as well as strategies used to determine believed fentanyl exposure and prevent overdose among 240 participants enrolled at a Chicago, IL syringe service program. Urinalysis measured actual fentanyl exposure. RESULTS: Most participants identified as African American (66.7%) and had considerable overdose experience (76.7% lifetime and 48% in the past year). Most also tested positive for fentanyl (93.75%) despite reporting no past year use of fentanyl or fentanyl-adulterated drugs (64.17%). The most utilized approaches reported for identifying fentanyl exposure were stronger effects of the drug (60.7%), sight or taste (46.9%), and being told by someone using the same drugs (34.2%). Few participants (14%) reported using fentanyl test strips. No significant associations were identified between self-report and urinalysis measures or urinalysis results and risk reduction strategies. CONCLUSION: This study adds to prior fentanyl exposure risk research. The disconnect between participants' fentanyl detection methods and reported overdose experiences supports the need for more research to identify and understand factors driving access and use of overdose prevention resources and strategies.

Examining the diagnostic value of the mnemonic discrimination task for classification of cognitive status and amyloid-beta burden.

Alzheimer's disease (AD) is the most common type of dementia, characterized by early memory impairments and gradual worsening of daily functions. AD-related pathology, such as amyloid-beta (Aß) plaques, begins to accumulate many years before the onset of clinical symptoms. Predicting risk for AD via related pathology is critical as the preclinical stage could serve as a therapeutic time window, allowing for early management of the disease and reducing health and economic costs. Current methods for detecting AD pathology, however, are often expensive and invasive, limiting wide and easy access to a clinical setting. A non-invasive, cost-efficient platform, such as computerized cognitive tests, could be potentially useful to identify at-risk individuals as early as possible. In this study, we examined the diagnostic value of an episodic memory task, the mnemonic discrimination task (MDT), for predicting risk of cognitive impairment or Aß burden. We constructed a random forest classification algorithm, utilizing MDT performance metrics and various neuropsychological test scores as input features, and assessed model performance using area under the curve (AUC). Models based on MDT performance metrics achieved classification results with an AUC of 0.83 for cognitive status and an AUC of 0.64 for Aß status. Our findings suggest that mnemonic discrimination function may be a useful predictor of progression to prodromal AD or increased risk of Aß load, which could be a cost-efficient, noninvasive cognitive testing solution for potentially wide-scale assessment of AD pathological and cognitive risk.

Conspicuous stripes on prey capture attention and reduce attacks by foraging jumping spiders.

Many animals avoid predation using aposematic displays that pair toxic/dangerous defences with conspicuous achromatic warning patterns, such as high-contrast stripes. To understand how these prey defences work, we need to understand the decision-making of visual predators. Here we gave two species of jumping spiders (Phidippus regius and Habronattus trimaculatus) choice tests using live termites that had their back patterns manipulated using paper capes (solid white, solid black, striped). For P. regius, black and striped termites were quicker to capture attention. Yet despite this increased attention, striped termites were attacked at lower rates than either white or black. This suggests that the termite's contrast with the background elicits attention, but the internal striped body patterning reduces attacks. Results from tests with H. trimaculatus were qualitatively similar but did not meet the threshold for statistical significance. Additional exploratory analyses suggest that attention to and aversion to stripes is at least partially innate and provide further insight into how decision-making played out during trials. Because of their rich diversity (over 6500 species) that includes variation in natural history, toxin susceptibility and degree of colour vision, jumping spiders are well suited to test broad generalizations about how and why aposematic displays work.

Pathways linking pulse pressure to dementia in adults with Down syndrome.

Individuals with Down syndrome (DS) are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease, entorhinal cortical atrophy, and diagnosis of dementia in adults with DS. Participants with DS from the Biomarkers of Alzheimer's Disease in Adults with Down Syndrome study (ADDS; n=195, age=50.6±7.2 years, 44% women, 18% diagnosed with dementia) were included. Higher pulse pressure was associated with greater global, parietal, and occipital WMH volume. Pulse pressure was not related to enlarged PVS, microbleeds, infarcts, entorhinal cortical thickness, or dementia diagnosis. However, in a serial mediation model, we found that pulse pressure was indirectly related to dementia diagnosis through parieto-occipital WMH and, subsequently through entorhinal cortical thickness. Higher pulse pressure may be a risk factor for dementia in people with DS by promoting cerebrovascular disease, which in turn affects neurodegeneration. Pulse pressure is an important determinant of brain health and clinical outcomes in individuals with Down syndrome despite the low likelihood of frank hypertension.

The Prevalence of Domestic Violence in the Lives of Female Heterosexual Partners of Sex Addicts.

This study provides evidence that rates of domestic violence (DV) run considerably higher in the lives of heterosexual women who identify as partners of sex addicts (PSAs) than in the general population. Data collected from 558 survey participants, from a variety of high-income nations, revealed that 92.1% had ever experienced any form of DV perpetrated by their partner and 57.7% had experienced physical and/or sexual intimate partner violence with their partner. The study also tests several hypotheses about sex addiction behaviors and PSA intimate partner violence (IPV), to help those working with these populations understand what factors may be contributing to, or mitigating, these women's experiences of violence.

Functional network structure supports resilience to memory deficits in cognitively normal older adults with amyloid-ß pathology.

Older adults may harbor large amounts of amyloid-ß (Aß) pathology, yet still perform at age-normal levels on memory assessments. We tested whether functional brain networks confer resilience or compensatory mechanisms to support memory in the face of Aß pathology. Sixty-five cognitively normal older adults received high-resolution resting state fMRI to assess functional networks, 18F-florbetapir-PET to measure Aß, and a memory assessment. We characterized functional networks with graph metrics of local efficiency (information transfer), modularity (specialization of functional modules), and small worldness (balance of integration and segregation). There was no difference in functional network measures between older adults with high Aß (Aß+) compared to those with no/low Aß (Aß-). However, in Aß+ older adults, increased local efficiency, modularity, and small worldness were associated with better memory performance, while this relationship did not occur Aß- older adults. Further, the association between increased local efficiency and better memory performance in Aß+ older adults was localized to local efficiency of the default mode network and hippocampus, regions vulnerable to Aß and involved in memory processing. Our results suggest functional networks with modular and efficient structures are associated with resilience to Aß pathology, providing a functional target for intervention.

Applying Principles of Evolutionary Biology to Plastic Surgery at an Organizational Level Predicts an Extinction Event.

As an organized profession, plastic surgery struggles delivering a clear message regarding scope of practice to patients given the diversity of procedures performed. Whereas granting licensure to practice medicine resides with governmental bodies, certification rests with organizations. However, certification is not required to practice plastic surgery. Since plastic surgery operationalizes techniques rather than working within a defined body organ, competition for patients is intense. Mapping territorial interactions between healthcare providers while parsing taxonomy elucidates individual, community, organizational, and governmental levels, creating various selection pressures. Applying evolutionary biology as a framework predicts the termination of plastic surgery over time as a unique specialty. An entirely new domain, Restorative Healthcare, is proposed which circumvents an extinction outcome.

Current attitudes toward drug checking services and a comparison of expected with actual drugs present in street drug samples collected from opioid users.

BACKGROUND: The opioid epidemic continues to be associated with high numbers of fatalities in the USA and other countries, driven mainly by the inclusion of potent synthetic opioids in street drugs. Drug checking by means of various technologies is being increasingly implemented as a harm reduction strategy to inform users about constituent drugs in their street samples. We assessed how valued drug checking services (DCS) would be for opioid street drug users given the ubiquity of fentanyl and related analogs in the drug supply, the information they would most value from drug checking, and compared expected versus actual constituent drugs in collected samples. METHODS: A convenience sample of opioid street drug users (N = 118) was recruited from two syringe service exchange programs in Chicago between 2021 and 2022. We administered brief surveys asking about overdose history, whether fentanyl was their preferred opioid, and interest in DCS. We also collected drug samples and asked participants what drug(s) they expected were in the sample. Provided samples were analyzed using LC-MS technology and the results compared to their expected drugs. RESULTS: Participants reported an average of 4.4 lifetime overdoses (SD = 4.8, range = 0-20) and 1.1 (SD = 1.8, range = 0-10) past-year overdoses. A majority (92.1%) believed they had recently used drugs containing fentanyl whether intentionally or unintentionally. Opinions about the desirability of fentanyl were mixed with 56.1% indicating they did not and 38.0% indicating they did prefer fentanyl over other opioids, mainly heroin. Attitudes toward DCS indicated a general but not uniform receptiveness with a majority indicating interest in DCS though sizeable minorities believed DCS was "too much trouble" (25.2%) or there was "no point" in testing (35.4%). Participants were especially inaccurate identifying common cutting agents and potentiating drugs such as diphenhydramine in their samples (sensitivity = .17). CONCLUSIONS: Results affirmed street drug users remain interested in using DCS to monitor their drugs and such services should be more widely available. Advanced checking technologies that provide information on the relative quantities and the different drugs present in a given sample available at point-of-care, would be most valuable but remain challenging to implement.

Feasibility study of using mobile phone-based experience sampling to assess drug checking by opioid street drug users.

BACKGROUND: To date, evaluations of take-home fentanyl (and/or benzodiazepine) test strip use - the most common form of drug checking services - and potential effects on overdose risk have relied on retrospective accounts for some preceding time period, usually a week to several months. Such accounts, however, are subject to recall and memory biases. This pilot study assessed the feasibility of using experiential sampling to collect daily information in situ on drug checking and associated overdose risk reduction - the primary outcomes - among a sample of street opioid users and compared the results to retrospective reports. METHODS: We recruited 12 participants from a Chicago-based syringe services program. Participants were 18 years of age or older, reported using opioids purchased on the street 3 + times per week in the past month, and had an available Android mobile phone. A phone-based app was programmed to collect daily drug checking information and provided to each participant along with a supply of fentanyl and benzodiazepine test strips and instructions for use over 21 days. Comparable retrospective data were collected via follow-up in-person surveys at the conclusion of daily report collection. RESULTS: We found a reasonably high rate of daily reporting (63.5%) with participants submitting reports on 160 "person-days" out of 252 possible days. Participants submitted daily reports an average of 13 of 21 days. Reports of test strip use frequency varied between the retrospective and daily reports with a relatively higher percentage of days/time using test strips obtained from the daily reports. We also found higher proportions reporting overdose risk reduction behaviors on the daily reports compared with the retrospective reviews. CONCLUSIONS: We believe the results support using daily experience sampling to collect information on drug checking behaviors among street drug users. Although resource intensive in comparison to retrospective reports, daily reporting potentially provides more detailed information on test strip use and its association with overdose risk reduction and, ultimately, fewer overdoses. Needed are larger trials and validation studies of daily experience sampling to identify the optimum protocol for collecting accurate information on drug checking and overdose risk reduction behavior.

Differential involvement of hippocampal subfields in the relationship between Alzheimer's pathology and memory interference in older adults.

Introduction: We tested whether Alzheimer's disease (AD) pathology predicts memory deficits in non-demented older adults through its effects on medial temporal lobe (MTL) subregional volume. Methods: Thirty-two, non-demented older adults with cerebrospinal fluid (CSF) (amyloid-beta [Aß]42/Aß40, phosphorylated tau [p-tau]181, total tau [t-tau]), positron emission tomography (PET; 18F-florbetapir), high-resolution structural magnetic resonance imaging (MRI), and neuropsychological assessment were analyzed. We examined relationships between biomarkers and a highly granular measure of memory consolidation, retroactive interference (RI). Results: Biomarkers of AD pathology were related to RI. Dentate gyrus (DG) and CA3 volume were uniquely associated with RI, whereas CA1 and BA35 volume were related to both RI and overall memory recall. AD pathology was associated with reduced BA35, CA1, and subiculum volume. DG volume and Aß were independently associated with RI, whereas CA1 volume mediated the relationship between AD pathology and RI. Discussion: Integrity of distinct hippocampal subfields demonstrate differential relationships with pathology and memory function, indicating specificity in vulnerability and contribution to different memory processes.

Patterns of opioid use behaviors among patients seen in the emergency department: Latent class analysis of baseline data from the POINT pragmatic trial.

INTRODUCTION: The nation's overdose epidemic has been characterized by increasingly potent opioids resulting in more emergency department (ED) encounters over time. ED-based opioid use interventions are growing in popularity; however, they tend to treat people who use opioids as a homogenous population. The current study sought to understand heterogeneity among people who use opioids who encounter the ED by identifying qualitatively different subgroups among participants in an opioid use intervention clinical trial at baseline and examining associations between subgroup membership and multiple correlates. METHODS: Participants were from a larger pragmatic clinical trial of the Planned Outreach, Intervention, Naloxone, and Treatment (POINT) intervention (n = 212; 59.2 % male, 85.3 % Non-Hispanic White, mean age = 36.6 years). The study employed latent class analysis (LCA) using five indicators of opioid use behavior: preference for opioids, preference for stimulants, usually use drugs alone, injection drug use, and opioid-related problem at ED encounter. Correlates of interest included participants' demographics, prescription histories, health care contact histories, and recovery capital (e.g., social support, naloxone knowledge). RESULTS: The study identified three classes: (1) noninjecting opioid preferers, (2) injecting opioid and stimulant preferers, and (3) social nonopioid preferers. We identified limited significant differences in correlates across the classes: differences existed for select demographics, prescription histories, and recovery capital but not for health care contact histories. For example, members of Class 1 were the most likely to be a race/ethnicity other than non-Hispanic White, oldest on average, and most likely to have received a benzodiazepine prescription, whereas members of Class 2 had the highest average barriers to treatment and members of Class 3 were the least likely to have been diagnosed with a major mental health illness and had the lowest average barriers to treatment. CONCLUSIONS: LCA identified distinct subgroups among POINT trial participants. Knowledge of such subgroups assists with the development of better-targeted interventions and can help staff to identify the most appropriate treatment and recovery pathways for patients.

Validated method for the analysis of 22 illicit drugs and their metabolites via liquid chromatography tandem mass spectrometry (LC-MS/MS) in illicit drug samples collected in Chicago, IL.

Drug checking services are being utilized worldwide to provide people who use drugs information on the composition and contents of their drugs as a tool for harm reduction and accidental overdose prevention. Existing drug checking services use a variety of techniques including immunoassay strips and spectroscopic techniques like FTIR and Raman. Few services utilize LC-MS based methods for primary or secondary analysis and few methods exist for direct analysis of illicit drugs. To address this, an LC-MS/MS method was developed for 22 illicit drugs and cutting agents using LC-MS/MS with application to 124 illicit drug samples that were collected from Chicago, IL. Samples were also analyzed using fentanyl and benzodiazepine immunoassay test strips. Fentanyl test strips gave a positive result for 86% of samples with only one sample showing a positive result on a benzodiazepine test strip. LC-MS/MS analysis of samples show that opioids were the most commonly quantified in 96% of samples, followed by stimulants at 12% and benzodiazepines at 1%. Fentanyl was measured in 91% of samples, co-occurring with heroin in 58% of opioid-containing samples. A comparison of the gold-standard LC-MS/MS results to fentanyl test strips shows a high level of accuracy for the fentanyl test strips, with just 5% of samples being classified as false negatives and no false positives. These results demonstrate the strengths and benefits of LC-MS/MS when incorporated as a secondary analysis tool for drug checking.

Cross-Section Observational Study to Assess Antimicrobial Resistance Prevalence among Bovine Respiratory Disease Bacterial Isolates from Commercial US Feedlots.

Antimicrobial resistance (AMR) is a global public health threat that jeopardizes efficacy of antibiotics in veterinary and human medicine. Antibiotics are commonly administered to target the bacterial component of bovine respiratory disease (BRD). The objectives of this study were to obtain a better understanding of antibiotic resistance in BRD-associated bacteria (Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni), investigate the clinical significance of AMR by monitoring clinical outcomes, and determine if regional differences exist in AMR trends. Deep pharyngeal swabs were used to sample beef cattle at initial BRD diagnosis (n = 453) from US feedlots representing three geographic regions. Organisms were identified by bacterial culture and subjected to broth microdilution antimicrobial susceptibility testing. Bacterium prevalence include P. multocida (36.0%), M. haemolytica (32.7%), and H. somni (28.5%). Of the Histophilus isolates, 39.5% were resistant to at least one antimicrobial, compared to 11.7% and 8.8% Pasteurella and Mannheimia, respectively. Non-susceptibility across all organisms was 5.7 X more likely in animals that received metaphylaxis, than those that did not (p < 0.0001; OR 5.7; CI 2.6-12.5). During days on feed 21-40, non-susceptibility of Histophilus was 8.7 X more likely than Mannheimia (p = 0.0002; OR 8.7; CI 2.8 to 27.4) and 6 X more likely than Pasteurella (p = 0.0016; OR 6.0; CI 2.0-18.0).