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Introduction: Hospitals are an ideal setting to stage opioid-related interventions with patients who are hospitalized due to overdose or other substance use-related complications. Transitional opioid programs-which initiate care and provide linkages upon discharge, such as screening, initiation of medications for opioid use disorder, and addiction consult services-have become the gold standard, but implementation has been uneven. The purpose of this study was to assess disparities in the availability of hospital-based transitional opioid programs, across rural and urban hospital settings in the United States., Methods: Using hospital administrative data paired with county-level demographic data, we conducted bivariate and regression analyses to assess rural-urban differences in the availability of transitional opioid services including screening, addiction consult services, and MOUD in U.S general medical centers, controlling for hospital- and community-level factors. Our sample included 2846 general medical hospitals that completed the 2021 American Hospital Association (AHA) Annual Survey of Hospitals. Our primary outcomes were five self-reported measures: whether the hospital provided screening in the ED; provided screening in the inpatient setting; whether the hospital provided addiction consult services in the ED; provided addiction consult services in the inpatient setting; and whether the hospital provided medications for opioid use disorder., Results: Rural hospitals did not have lower odds of screening for OUD or other SUDs than urban hospitals, but both micropolitan rural counties and noncore rural counties had significantly lower odds of having addiction consult services in either the ED (OR: 0.74, 95 % CI: 0.58, 0.95; OR: 0.68, 95 % CI: 0.50, 0.91) or inpatient setting (OR: 0.76, 95 % CI: 0.59, 0.97; OR: 0.68, 95 % CI: 0.50, 0.93), respectively, or of offering MOUD (OR: 0.69, 95 % CI: 0.52, 0.90; OR: 0.52, 95 % CI: 0.37, 0.74)., Conclusions: Our study suggests that evidence-based interventions, such as medications for opioid use disorder and addiction consult services, are less often available in rural hospitals, which may contribute to rural-urban disparities in health outcomes secondary to OUD. A priority for population health improvement should be developing implementation strategies to support rural hospital adoption of transitional opioid programs., Competing Interests: Declaration of competing interest None of the authors have conflicts of interest to report., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Socioeconomic and geographic determinants of medical school application and matriculation may help explain the unequal distribution of physicians in the United States. This study describes trends in MD-granting medical school application and matriculation rates and explores the relationship between county median family income, proximity to a medical school, and medical school application and matriculation rates., Method: Data were obtained from the Association of American Medical Colleges, including the age, gender, and Federal Information Processing Standards code for county of legal residence for each applicant and matriculant to U.S. MD-granting medical schools from 2001 through 2015. The application and matriculation rates in each county were calculated using the number of applicants and matriculants per 100,000 residents. Counties were classified into 4 groups according to the county median family income (high-income, middle-income, middle-low-income, low-income). The authors performed chi-square tests to assess trends across the study period and the association of county median family income with application and matriculation rates., Results: There were 581,833 applicants and 262,730 (45.2%) matriculants to MD-granting medical schools between 2001 and 2015. The application rates per 100,000 residents during 2001-2005, 2006-2010, and 2011-2015 were 57.2, 62.7, and 69.0, respectively, and the corresponding matriculation rates were 27.5, 28.1, and 29.8. The ratios of the application rate in high-income counties to that in low-income counties during the 3 time periods were 1.9, 2.4, and 2.8, respectively., Conclusions: The application and matriculation rates to MD-granting medical schools increased steadily from 2001 to 2015. Yet, applicants and matriculants disproportionately came from high-income counties. The differences in the application and matriculation rates between low-income and high-income counties grew during this period. Exploring these differences can lead to better understanding of the factors that drive geographic differences in physician access and the associated health disparities across the United States., (Copyright © 2021 by the Association of American Medical Colleges.)

Generation of high-affinity IgG is essential for defense against infections and cancer, which is the intended consequence of many vaccines, but can cause autoimmune and inflammatory diseases when inappropriately directed against self. The interplay of T follicular helper (T FH ) cells and T follicular regulatory (T FR ) cells is critical for the production of high-affinity IgG of a specific subclass. In this study, we sought to improve Ag-specific IgG responses with two interventions intended to transiently diminish T FR cell influence. First, adult mice were administered an antibiotic mixture (ABX) for an extended period to deplete the immunoregulatory intestinal microbiota. This intriguingly increased T FH cell and reduced T FR cell numbers. 2,4,6-Trinitrophenyl hapten conjugated to keyhole limpet hemocyanin immunization resulted in higher affinity 2,4,6-trinitrophenyl hapten-specific IgG1 in ABX mice compared with controls. In a model of IgG-driven inflammatory nephritis, ABX mice had significantly worse nephritis accompanied by higher affinity Ag-specific IgG2b and enriched T FH cells compared with controls. Second, we sought to functionally manipulate T FH and T FR cells, which both express the checkpoint inhibitory molecule, PD-1, by administration of anti-PD-1 during immunization. This intervention enhanced the affinity of Ag-specific IgG of the appropriate subclass and increased in T FH cells following 2,4,6-trinitrophenyl hapten conjugated to keyhole limpet hemocyanin immunization and nephritis induction. These results suggest that altering T FH and T FR cell ratios during immunization is an appealing strategy to qualitatively improve Ag- and subclass-specific IgG responses., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Objectives: Hospitals are on the front lines of the opioid epidemic, seeing patients who overdose or have complicated infections, but the extent of services offered or whether services are evidence-based is not known. The objective of our study was to assess the extent to which nonprofit hospitals are addressing opioid abuse, a critical public health issue, through their community benefit work and to identify which evidence-based strategies they adopt., Methods: We reviewed community benefit documents from January 1, 2015, through December 31, 2018, for a sample (N = 446) of all nonprofit hospitals in the United States. We classified hospital opioid-related strategies into 9 categories. Using logistic regression, we predicted the likelihood of hospitals adopting various strategies to address opioid abuse., Results: Of the 446 nonprofit hospitals in our sample, 49.1% (n = 219) adopted ≥1 clinical strategy to address opioid use disorder in their community. Approximately one-quarter (26.5%; n = 118) of hospitals adopted a strategy related to treatment services for substance use disorder; 28.2% (n = 126) had ≥1 program focused on connecting patients to a primary care medical home, and 14.6% (n = 65) focused on caring for patients with opioid-related overdoses in the emergency department. We also identified factors that predicted involvement in programs that were less common than clinical strategies, but potentially effective, such as harm reduction and prescriber initiatives (both 6.3% of hospitals)., Conclusions: Evidence-based prevention and treatment require strong collaboration between health care and community institutions at all levels. Effective policy interventions may exist to encourage various types and sizes of nonprofit hospitals to adopt evidence-based interventions to address opioid abuse in their communities.

Approximately 25 million people in the United States are limited English proficient (LEP). Appropriate language services can improve care for LEP individuals, and health care facilities receiving federal funds are required to provide such services. Recognizing the risk of inadequate comprehension of prescription medication instructions, between 2008 and 2012, New York City and State passed a series of regulations that require chain pharmacies to provide translated prescription labels and other language services to LEP patients. We surveyed pharmacists before (2006) and after (2015) implementation of the regulations to assess their impact in chain pharmacies. Our findings demonstrate a significant improvement in capacity of chains to assist LEP patients. A higher proportion of chain pharmacies surveyed in 2015 reported printing translated labels, access and use of telephone interpreter services, multilingual signage, and documentation of language needs in patient records. These findings illustrate the potential impact of policy changes on institutional practices that impact large and vulnerable portions of the population.

Objective: Observations of microbial dysbiosis in patients with rheumatoid arthritis (RA) have raised interest in studying microbial-mucosal interactions as a potential trigger of RA. Using the murine collagen-induced arthritis (CIA) model, we undertook this study to test our hypothesis that microbiota modulate immune responses leading to autoimmune arthritis., Methods: CIA was induced by immunization of mice with type II collagen (CII) in adjuvant on days 0 and 21, with arthritis appearing on days 23 and 24. Intestinal microbiota were profiled by 16S ribosomal RNA sequencing every 7 days during the course of CIA, and intestinal mucosal changes were evaluated on days 14 and 35. Then, microbiota were depleted either early (7 days before immunization) or late (day 21 after immunization) by administration of broad-spectrum antibiotics. Disease severity, autoantibody and systemic cytokine production, and intestinal mucosal responses were monitored in the setting of microbial reduction., Results: Significant dysbiosis and mucosal inflammation occurred early in CIA, prior to visible arthritis, and continued to evolve during the course of disease. Depletion of the microbiota prior to the induction of CIA resulted in an ~40% reduction in disease severity and in significantly reduced levels of serum inflammatory cytokines and anti-CII antibodies. In intestinal tissue, production of interleukin-17A (IL-17A) and IL-22 was delayed. Unexpectedly, microbial depletion during the late phase of CIA resulted in a >50% decrease in disease severity. Anti-CII antibodies were mildly reduced but were significantly impaired in their ability to activate complement, likely due to altered glycosylation profiles., Conclusion: These data support a model in which intestinal dysbiosis triggers mucosal immune responses that stimulate T and B cells that are key for the development of inflammatory arthritis., (© 2018, American College of Rheumatology.)

Self-reactive IgGs contribute to the pathology of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Paradoxically, IgGs are used to treat inflammatory diseases in the form of high-dose intravenous immunoglobulin (IVIG). Distinct glycoforms on the IgG crystallizable fragment (Fc) dictate these divergent functions. IgG anti-inflammatory activity is attributed to sialylation of the Fc glycan. We therefore sought to convert endogenous IgG to anti-inflammatory mediators in vivo by engineering solubilized glycosyltransferases that attach galactose or sialic acid. When both enzymes were administered in a prophylactic or therapeutic fashion, autoimmune inflammation was markedly attenuated in vivo. The enzymes worked through a similar pathway to IVIG, requiring DC-SIGN, STAT6 signaling, and FcγRIIB. Importantly, sialylation was highly specific to pathogenic IgG at the site of inflammation, driven by local platelet release of nucleotide-sugar donors. These results underscore the therapeutic potential of glycoengineering in vivo., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Epigenetic "readers" that recognize defined posttranslational modifications on histones have become desirable therapeutic targets for cancer and inflammation. SP140 is one such bromodomain- and plant homeodomain (PHD)-containing reader with immune-restricted expression, and single-nucleotide polymorphisms (SNPs) within SP140 associate with Crohn's disease (CD). However, the function of SP140 and the consequences of disease-associated SP140 SNPs have remained unclear. We show that SP140 is critical for transcriptional programs that uphold the macrophage state. SP140 preferentially occupies promoters of silenced, lineage-inappropriate genes bearing the histone modification H3K27me3, such as the HOXA cluster in human macrophages, and ensures their repression. Depletion of SP140 in mouse or human macrophages resulted in severely compromised microbe-induced activation. We reveal that peripheral blood mononuclear cells (PBMCs) or B cells from individuals carrying CD-associated SNPs within SP140 have defective SP140 messenger RNA splicing and diminished SP140 protein levels. Moreover, CD patients carrying SP140 SNPs displayed suppressed innate immune gene signatures in a mixed population of PBMCs that stratified them from other CD patients. Hematopoietic-specific knockdown of Sp140 in mice resulted in exacerbated dextran sulfate sodium (DSS)-induced colitis, and low SP140 levels in human CD intestinal biopsies correlated with relatively lower intestinal innate cytokine levels and improved response to anti-tumor necrosis factor (TNF) therapy. Thus, the epigenetic reader SP140 is a key regulator of macrophage transcriptional programs for cellular state, and a loss of SP140 due to genetic variation contributes to a molecularly defined subset of CD characterized by ineffective innate immunity, normally critical for intestinal homeostasis., (Copyright © 2017, American Association for the Advancement of Science.)

Immunoglobulin ε (IgE) antibodies are the primary mediators of allergic diseases, which affect more than 1 in 10 individuals worldwide. IgE specific for innocuous environmental antigens, or allergens, binds and sensitizes tissue-resident mast cells expressing the high-affinity IgE receptor, FcεRI. Subsequent allergen exposure cross-links mast cell-bound IgE, resulting in the release of inflammatory mediators and initiation of the allergic cascade. It is well established that precise glycosylation patterns exert profound effects on the biological activity of IgG. However, the contribution of glycosylation to IgE biology is less clear. Here, we demonstrate an absolute requirement for IgE glycosylation in allergic reactions. The obligatory glycan was mapped to a single N-linked oligomannose structure in the constant domain 3 (Cε3) of IgE, at asparagine-394 (N394) in human IgE and N384 in mouse. Genetic disruption of the site or enzymatic removal of the oligomannose glycan altered IgE secondary structure and abrogated IgE binding to FcεRI, rendering IgE incapable of eliciting mast cell degranulation, thereby preventing anaphylaxis. These results underscore an unappreciated and essential requirement of glycosylation in IgE biology., (© 2015 Shade et al.)

The USA leads the developed world in motor vehicle fatalities, presenting a critical public health threat. We examined whether an increasing share of mass transit use, relative to vehicle miles traveled on public roads, was associated with reduced motor vehicle fatalities. We used annual city-level data for the USA from 1982-2010 provided by the Fatality Accident Reporting System, the Texas A&M Transportation Institute, the Census Bureau, and the National Oceanic and Atmospheric Administration to estimate a structural equation model of the factors associated with mass transit miles and motor vehicle fatalities. The final analytic data included 2,900 observations from 100 cities over 29 years. After accounting for climate, year, and the economic costs of driving, an increasing share of mass transit miles traveled per capita was associated with reduced motor vehicle fatalities. The costs of congestion to the average commuter and gas prices were positively associated with increasing the share of mass transit miles traveled. The economic costs of driving increased over time, while both the fatality rate and the share of mass transit miles traveled decreased over time. Increasing the share of mass transit miles traveled may be associated with fewer motor vehicle miles traveled. Increasing mass transit uptake may be an effective public health intervention to reduce motor vehicle fatalities in cities.

Background: This study compared differences in cholesterol screening among immigrant populations and US born race/ethnic groups and whether improving access to health care reduced differences in screening., Methods: Self-reported cholesterol screening for adults was calculated from multivariate logistic regression analysis of the 1988-2008 National Health and Nutrition Examination Surveys (N = 17,118). Immigrant populations were classified by place of birth and length of residency., Results: After adjusting for individual characteristics and access to health care, the multivariate adjusted probability of cholesterol screening is significantly lower for persons originating from Mexico (70.9%) compared to persons born in the US (80.1%) or compared to US born Hispanic persons (77.8%). Adjustment for access to care did significantly reduce the difference in screening rates between immigrants and natives because the rate for natives remained the same, but the rate for immigrants improved. For example, the difference in screening between US born persons and persons born in Mexico was reduced by nearly 10% after adjustment for access to care., Conclusions: There are persistent disparities in cholesterol screening for immigrants, particularly recent immigrants from Mexico, but improved access to health care may be a viable policy intervention to reduce disparities.

Objective: To examine the effect of an integrated, clinician-focused telehealth monitoring system on the probability of hospitalization within the first 30-day episode of home healthcare., Study Design: Retrospective, nonexperimental design., Methods: The study sample includes 2009 data from 5873 Medicare beneficiaries receiving home healthcare services through a network of community-based home health agencies operating in Texas and Louisiana. Propensity-score matching was used to control for selection bias. Logistic regression and postestimation parameter simulation were used to assess how the use of an integrated, clinician-focused telehealth monitoring system might affect the probability of hospitalization during the first 30-day episode of home healthcare., Results: The 30-day probability of hospitalization for telehealth and non-telehealth patients was 10.3% and 17.1%, respectively. Patients in the telehealth group had a 7-percentage-point (95% confidence interval 4.2, 9.4) lower probability of hospitalization within the first 30-day episode of home healthcare than those in the non-telehealth group., Conclusion: The use of an integrated, clinician focused telehealth monitoring system can substantially reduce the 30-day probability of hospitalization for home healthcare patients. Telehealth monitoring systems that integrate skilled clinicians can lead to substantial hospitalization-related cost savings.

Objective: To determine whether labor market effects were the result of diabetes per se or rather depended on the degree to which diabetes was controlled through management of blood sugar levels., Methods: This study utilized data from a recently completed survey of households in Brownsville, Texas, a largely Mexican American community with a high prevalence of diabetes that is located on the Texas-Mexico border. Diabetes management, or control, was measured by blood sugar levels, glycosylated hemoglobin (A1C) levels, and interaction terms. Methods used were probit and Heckman regression., Results: Management of diabetes did not appear to have a discernible impact on labor market outcomes in the short run. However, diabetes was negatively associated with male productivity, particularly in males' propensity to work. The new American Diabetes Association (ADA) definition of diabetes is based on having an A1C level of <6.5%. Using the new ADA definition, diabetes was negatively associated with female productivity. Female productivity was also negatively associated with the new ADA definition of prediabetes (A1C levels between 5.7% and 6.4%). However, very few people with diabetes actually controlled their blood sugar or A1C levels., Conclusion: These results imply that in order to avoid productivity losses associated with diabetes, more scarce prevention resources should be spent on prevention of the onset of diabetes than on the management of A1C for those already diagnosed with diabetes. For women, the prevention of prediabetes is key.

Objective: To provide follow-up in patients treated with pharmacomechanical thrombolysis (PhMT) for lower extremity deep venous thrombosis (DVT)., Methods: Retrospective analysis of prospectively collected data. Patients underwent clinical evaluation, duplex ultrasound, venous clinical severity scoring, venous segmental disease scoring, and venous disability scoring., Results: Fourteen patients were available for evaluation. Median age was 40 years (19-58). Median follow-up was 24 months (13-69 months). Thirteen of 14 patients (93%) had a venous disability score < 1 and 13 of 14 patients (93%) had a venous clinical severity scoring < 5. In all but 1 patient the venous segmental disease scoring score was < 5. All iliac segments were patent, all but 3 patients had partial infrainguinal obstruction and 5 of 14 (36%) had reflux., Conclusions: Our data demonstrate that the good early clinical results after PhMT can be sustained on longer follow-up and may prevent the development of advanced postthrombotic syndrome.

We present 2 cases of hemorrhage from a visceral artery pseudoaneurysm, managed successfully with endovascular covered stent placement. The first case was a 59-year-old man, 3 months after a laparoscopic distal pancreatectomy for adenoma, presenting with diffuse abdominal pain. The patient was evaluated with a computed tomography scan revealing a splenic artery pseudoaneurysm (PA) bleeding into a pancreatic pseudocyst. He was emergently taken to the angiography suite where a covered stent was deployed at the level of splenic artery PA. The second case was a 52-year-old woman with recurrent left retroperitoneal mass 5 years after distal pancreatectomy and splenectomy for a nonfunctional neuroendocrine tumor. She underwent resection of the mass in the left upper quadrant. Postoperative course was complicated by hematoma, abscess formation, reexploration, and repair of the duodenotomy and the portal vein. Subsequently, she was noted to have intermittent gastrointestinal hemorrhage, which prompted an angiogram revealing a hepatic artery PA that was repaired with a covered balloon-expandable stent. A completion angiogram was obtained in each case demonstrating exclusion of the PA. Our experience with these 2 cases supports the notion that endovascular covered stenting is a safe and effective therapy for exclusion of visceral artery aneurysm.

Current diagnostic testing for cardiovascular pathology usually rests on either physiological or anatomic measurement. Multiple tests must then be combined to arrive at a conclusion regarding treatment of a specific pathology. Much of the diagnostic decisions currently made are based on rough estimates of outcomes, often derived from gross anatomic observations or extrapolation of physical laws. Thus, intervention for carotid and coronary disease is based on estimates of diameter stenosis, despite data to suggest that plaque character and lesion anatomy are important determinants of outcome. Similarly, abdominal aortic aneurysm (AAA) intervention is based on maximal aneurysm diameter without regard for arterial wall composition or individual aneurysm geometry. In other words, our current diagnostic tests do not reflect the sophistication of our current knowledge of vascular disease. Using a multimodal approach, computer modeling has the potential to predict clinical outcomes based on a variety of factors including arterial wall composition, surface anatomy and hemodynamic forces. We term this more sophisticated approach "patient specific diagnostics", in which the computer models are reconstructed from patient specific clinical visualizing modalities, and material properties are extracted from experimental measurements of specimens and incorporated into the modeling using advanced material models (including nonlinear anisotropic models) and performed as dynamic simulations using the FSI (fluid structure interaction) approach. Such an approach is sorely needed to improve the effectiveness of interventions. This article will review ongoing work in "patient specific diagnostics" in the areas of carotid, coronary and aneurismal disease. We will also suggest how this approach may be applicable to management of aortic dissection. New diagnostic methods should allow better patient selection, targeted intervention and modeling of the results of different therapies.

available at http://www.neurology.org/cgi/ content/abstract/68/3/195.