Internal Medicine Resident Addiction Training at the Veteran's Health Administration: A Qualitative Evaluation of Site Directors' Response to the 2022 ACGME Requirements.

BACKGROUND: Substance use disorders (SUDs) are prevalent in the USA yet remain dramatically undertreated. To address this care gap, the Accreditation Council for Graduate Medical Education (ACGME) approved revisions to the Program Requirements for Graduate Medical Education (GME) in Internal Medicine, effective July 1, 2022, requiring addiction medicine training for all internal medicine (IM) residents. The Veterans Health Administration (VHA) is a clinical training site for many academic institutions that sponsor IM residencies. This focus group project evaluated VHA IM residency site directors' perspectives about providing addiction medical education within VHA IM training sites. OBJECTIVE: To better understand the current state, barriers to, and facilitators of IM resident addiction medicine training at VHA sites. DESIGN: This was a qualitative evaluation based on semi-structured video-based focus groups. PARTICIPANTS: Participants were VHA IM site directors based at a VHA hospital or clinic throughout the USA. APPROACH: Focus groups were conducted using a semi-structured group interview guide. Two investigators coded each focus group independently, then met to create a final adjudicated coding scheme. Thematic analysis was used to identify key themes. KEY RESULTS: Forty-three participants from 38 VHA sites participated in four focus groups (average size: 11 participants). Six themes were identified within four pre-defined categories. Current state of training: most VHA sites offered no formal training in addiction medicine for IM residents. Barriers: addiction experts are often located outside of IM settings, and ACGME requirements were non-specific. Facilitators: clinical champions help support addiction training. Desired next steps: participants desired incentives to train or hire local champions and a pre-packaged didactic curriculum. CONCLUSIONS: Developing competent clinical champions and leveraging VHA addiction specialists from non-IM settings would create more addiction training opportunities for IM trainees at VHA sites. These insights can likely be applied to IM training at non-VHA sites.

A First Look at the VA MISSION Act Veteran Health Administration Medical School Scholarship and Loan Repayment Programs.

Background: The US Department of Veterans Affairs (VA) is challenged by physician staffing shortages. The 2018 VA MISSION ACT authorized 2 scholarship and loan repayment programs. The Health Professions Scholarship Program (HPSP) created scholarships for physicians and dentists. The Education Debt Reduction Program (EDRP) increased the maximum debt reduction. The Specialty Education Loan Repayment Program (SELRP) authorized the repayment of educational loans for physicians in specialties deemed necessary for VA. The Veterans Healing Veterans (VHV) program was a 1-year pilot program specifically for veteran medical students. Observations: For academic years 2020/2021 and 2021/2022, HPSP offered 54 scholarships with 51 accepted. In 2020, the VHV program offered 22 scholarships with 12 accepted by recipients at all 5 Teague-Cranston medical schools and 4 Historically Black Colleges and Universities. For SELRP, 14 applicants have been approved in family medicine, internal medicine, emergency medicine, and geriatrics. The average loan repayment is anticipated to be $110,000, which equates to 38.5 VA service years for the 14 applicants. Since 2018, 1546 physicians received EDRP awards with amounts increased from an average of $96,090 in 2018 to $148,302 in 2020. Conclusions: The VA MISSION Act's scholarship and loan repayment programs provide VA with several ways to address physician workforce shortages. Ultimately, the success of the program will be determined by the recruitment of scholarship recipients to VA careers.

The Regional Distribution of Psychiatric Residency Positions Funded by the Department of Veterans Affairs and Its Relationship to Rural Veteran Populations.

OBJECTIVE: The authors evaluated the distribution of psychiatry residency positions funded by the Department of Veterans Affairs between 2014 and 2020 with respect to geographic location and hospital patient population rurality. METHODS: The authors collected data on psychiatry residency positions from the Veterans Affairs' Office of Academic Affiliations Support Center and data on hospital-level patient rurality from the Veterans Health Administration Support Service Center. They examined the chronological and geospatial relationships between the number of residency positions deployed and the size of the rural patient populations served. RESULTS: Between 2014 and 2020, the Department of Veterans Affairs has substantially increased the number of rural hospitals hosting psychiatry residency programs, as well as the number of residency positions at those hospitals. However, several geographic regions serve high numbers of rural veterans with few or no psychiatry resident positions. CONCLUSIONS: While the VA efforts to increase psychiatry residency positions in rural areas have been partially successful, additional progress can be made increasing support for psychiatry trainees at Veterans Affairs hospitals and community-based outpatient clinics that serve large portions of the rural veteran population.

Veterans Affairs Graduate Medical Education Expansion Addresses U.S. Physician Workforce Needs.

The United States has a well-trained, highly specialized physician workforce yet continues to have care gaps across the nation. Deficiencies in primary care and mental health specialties are most frequently cited, though critical shortages in multiple disciplines exist, particularly in rural areas. Sponsoring institutions of physician graduate medical education (GME) have created rural residency tracks with modest federal funding and minimal incentives, though efforts targeting shortages in these specialties and geographic locations have been limited. In response to access problems in the Veterans Health Administration, Department of Veterans Affairs (VA), the second largest federal funder of GME with the most expansive clinical education platform, Congress passed the Veterans Access, Choice, and Accountability Act of 2014. This act directed the VA and provided funding to establish 1,500 new positions, a 15% expansion of VA-funded positions at the time. Priority for position selection was given to primary care, mental health, and any other specialties the secretary of VA determined appropriate. Importantly, priority was also given to VA facilities with documented physician shortages, those that did not have GME training programs, those in communities with high concentrations of veterans, and those in health profession shortage areas. Many rural facilities match this profile and were targeted for this initiative. At the conclusion of fiscal year 2021, 1,490 positions had been authorized, and 21 of the 22 VA medical centers previously without GME activity had added residents or were planning to soon. Of the authorized positions, 42% are in primary care, 24% in mental health, and 34% in critically needed additional specialties. Targeted GME expansion in the VA, the largest integrated health care system in the nation, has been successful in addressing physician GME training that aligns with physician shortages and may serve as a model to address national physician specialty and geographic workforce needs.

Program Profile: The Expansion of Associated Health Training in the VA.

PURPOSE: Approximately 21,000 US Department of Veterans Affairs (VA) health professions trainees per year are in associated health (AH) occupations. We describe the VA Office of Academic Affiliation's expansion of AH education in recent years and highlight the importance of increasing AH education broadly in the United States. Our focus is on the growing role of AH education in the VA over the past decade by describing the demand for AH professionals in all clinical settings; scope of funded AH training in the VA; and targeted AH education expansion efforts. OBSERVATIONS: The VA provides clinical training for more than 40 AH professions and provides funding for 17 of these professions. Expansion efforts in AH over the past 10 years have yielded a 33% increase in stipend-funded positions and targeted interprofessional training, VA strategic initiatives, rural populations, and conversion of pregraduate-degree positions to postgraduate-degree positions. CONCLUSIONS: In order to meet the complex health care needs of our nation, continued attention to interprofessional care and health professions education is of paramount importance. The VA has worked to address these broad needs and to meet the needs of veterans through increasing stipend-funded AH training positions by 33% and directly targeting high-need clinical areas. Ongoing expansion is anticipated in the areas of postgraduate-degree training and rural training.

Guidelines Have a Key Role in Driving HCV Elimination by Advocating for Simple HCV Care Pathways.

The availability of pangenotypic direct-acting antivirals for treatment of hepatitis C (HCV) has provided an opportunity to simplify patient pathways. Recent clinical practice guidelines have recognised the need for simplification to ensure that elimination of HCV as a public health concern remains a priority. Despite the move towards simplified treatment algorithms, there remains some complexity in the recommendations for the management of genotype 3 patients with compensated cirrhosis. In an era where additional clinical trial data are not anticipated, clinical guidance should consider experience gained in real-world settings. Although more experience is required for some pangenotypic therapeutic options, on the basis of published real-world data, there is already sufficient evidence to consider a simplified approach for genotype 3 patients with compensated cirrhosis. The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need to minimise the need for complex patient pathways and clinical practice guidelines need to continue to evolve in order to ensure that patient outcomes remain optimised.

Delayed gastrointestinal-associated lymphoid tissue reconstitution in duodenum compared with rectum in HIV-infected patients initiating antiretroviral therapy.

BACKGROUND: We aimed to characterize the impact of antiretroviral therapy (ART) initiation on gastrointestinal-associated lymphoid tissue at various sites along the gastrointestinal site. METHODOLOGY: Peripheral blood and duodenal and rectal biopsies were obtained from 12 HIV to 33 treatment-naive HIV participants at baseline and after 9 months ART. Tissue was digested for immunophenotyping. Inflammatory, bacterial translocation and intestinal damage markers were measured in plasma. RESULTS: Twenty-six HIV patients completed follow-up. The lowest reconstitution of CD4 T cells and the lowest CD4/CD8 ratio during ART compared with blood were observed in the duodenum with the rectum being either intermediate or approaching blood levels. Regulatory T cells were in higher proportions in the duodenum than the rectum and neither declined significantly during ART. Several correlations with biomarkers of microbial translocation were observed including increases in lipoteichoic acid levels, which reflects Gram-positive bacterial translocation, correlated with increases in %CD4 T cells in the duodenum (Rho 0.773, P = 0.033), and with decreases in duodenal regulatory T-cell populations (Rho -0.40, P = 0.045). CONCLUSION: HIV-mediated immunological disruption is greater in the duodenum than rectum and blood before and during ART. Small intestine damage may represent a unique environment for T-cell depletion, which might be attenuated by interaction with Gram-positive bacteria.

A Year 3 Progress Report on Graduate Medical Education Expansion in the Veterans Access, Choice, and Accountability Act.

The VA has made progress in implementing mandates to expand medical residency programs to more rural and underserved locations and to increase access to family care providers, but some specialties, like geriatrics, remain underrepresented.

Correction: Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial.

[This corrects the article DOI: 10.1371/journal.ppat.1005381.].

Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial.

Whether initiation of antiretroviral therapy (ART) regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT) impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV- controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by high-performance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6), lipoteichoic acid (LTA), soluble CD14 (sCD14) and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8+ T-cell density decline, greater normalization of mucosal CCR5+CD4+ T-cells and increase of the naïve/memory CD8+ T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively), with no changes in HIV RNA in plasma or tissue. Maraviroc showed the highest drug distribution to the gut tissue, and duodenal concentrations correlated well with other T-cell markers in duodenum, i.e., the CD4/CD8 ratio, %CD4+ and %CD8+ HLA-DR+CD38+ T-cells. Maraviroc use elicited greater activation of the mucosal naïve CD8+ T-cell subset, ameliorated the distribution of the CD8+ T-cell maturational subsets and induced higher improvement of zonulin-1 levels. These data suggest that combined CCR5 and integrase inhibitor based combination therapy in ART treatment naïve patients might more effectively reconstitute duodenal immunity, decrease inflammatory markers and impact on HIV persistence by cell-dependent mechanisms, and show unique effects of MVC in duodenal immunity driven by higher drug tissue penetration and possibly by class-dependent effects.

Role of intestinal myofibroblasts in HIV-associated intestinal collagen deposition and immune reconstitution following combination antiretroviral therapy.

OBJECTIVE: To investigate the potential role of mucosal intestinal myofibroblasts (IMFs) in HIV and associated fibrosis in gut-associated lymphoid tissue. DESIGN: Profibrotic changes within the secondary lymphoid organs and mucosa have been implicated in failed immune reconstitution following effective combination antiretroviral therapy (cART). Microbial translocation is believed to be sustaining these systemic inflammatory pathways. IMFs are nonprofessional antigen-presenting cells with both immunoregulatory and mesenchymal functions that are ideally positioned to respond to translocating microbial antigen. METHODS: Duodenal biopsies, obtained from patients naive to cART, underwent trichrome staining and were examined for tissue growth factor-beta (TGF-ß) expression. Combined immunostaining and second harmonic generation analysis were used to determine IMF activation and collagen deposition. Confocal microscopy was performed to examine IMF activation and Toll-like receptor (TLR)4 expression. Finally, primary IMF cultures were stimulated with lipopolysaccharide to demonstrate the expression of the inflammatory biomarkers. RESULTS: The expression of the fibrosis-promoting molecule, TGF-ß1, is significantly increased in duodenal biopsies from HIV patients naïve to cART, and negatively correlated with subsequent peripheral CD4(+) recovery. The increase in TGF-ß1 coincided with an increase in collagen deposition in the duodenal mucosa in the tissue area adjacent to the IMFs. We also observed that IMFs expressed TLR4 and had an activated phenotype since they were positive for fibroblast activation protein. Finally, stimulation of IMFs from HIV patients with TLR4 resulted in significantly increased expression of profibrotic molecules, TGF-ß1, and interleukin-6. CONCLUSION: Our data support the hypothesis that activated IMFs may be among the major cells contributing to the profibrotic changes, and thus, the establishment and maintenance of systemic inflammation interfering with immune reconstitution in HIV patients.

The Epidemiology of Fifth Metatarsal Fracture.

BACKGROUND: A paucity of data exists studying the epidemiology of fifth metatarsal fractures. While a number of studies exist focusing on specific fracture patterns and patient populations, a large comprehensive epidemiologic study on the general public does not. OBJECTIVE: We reviewed 1275 fifth metatarsal fractures treated at a multicenter orthopaedic practice attempting to classify mechanism of injury and patient demographics as they pertain to specific fracture patterns. METHODS: Patient demographics were recorded and fractures categorized by location and mechanism of injury. Demographics and mechanism of injury were assessed to determine their predictive value for the type of fracture. Statistical analysis was used to predict whether demographics and mechanism of injury were statistically significant for types of fractures and whether gender and age were positive predictive values for fifth metatarsal fractures. RESULTS: Twisting injuries were a statistically significant predictor of zone 1 injuries. A significant correlation between gender and fracture location was seen with women sustaining 75% of zone 1 injuries and 84% of dancer's fractures. A positive predictive value existed for age and gender with respect to the incidence of fractures. Males accounted for more fractures among younger patients and females accounting for the majority of fractures among older patients. CONCLUSION: Mechanism of injury is a predictor for fracture location. Gender and age have a role in fracture incidence. In younger patient populations, males account for the majority of fifth metatarsal fractures. In older patient populations, females account for the majority of fifth metatarsal fractures. LEVEL OF EVIDENCE: Prognostic study, Level II: Retrospective Study.

Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy.

OBJECTIVES: To examine the impact of serum-derived bovine immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy. DESIGN: Open-label trial with intensive 8-week phase of bovine serum immunoglobulin (SBI) 2.5 g twice daily with a 4-week washout period and an optional 9-month extension study. METHODS: HIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastrointestinal questionnaire assessed changes in symptoms. RESULTS: All eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P = 0.008) and improvements in stool consistency (P = 0.008). Gut permeability was normal before and after the intervention, but D-xylose absorption increased in seven of eight participants. Mucosal CD4 lymphocyte densities increased by a median of 139.5 cells/mm2 from 213 to 322 cells/mm2 (P = 0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (P = 0.039), and then fell below baseline in four of five who continued receiving SBI (P = 0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4 lymphocyte densities (r = -0.74, P = 0.046). CONCLUSION: SBI significantly increases intestinal mucosal CD4 lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the setting of HIV enteropathy.

Management of alcohol abuse.

This article reviews the spectrum of alcohol use disorders. The pharmacologic properties of ethanol and its metabolism, and the historical, physical, and laboratory elements that may help diagnose an alcohol use disorder are examined. The concepts of motivational interviewing and stages of change are mentioned, along with the American Society of Addiction Medicine patient placement criteria, to determine the best level of treatment for alcoholism. Various therapeutic management options are reviewed, including psychological, pharmacologic, and complementary/alternative choices. This article provides a basic understanding of available tools to diagnose and treat this cunning and baffling brain and multisystem disease.

Gastrointestinal-associated lymphoid tissue immune reconstitution in a randomized clinical trial of raltegravir versus non-nucleoside reverse transcriptase inhibitor-based regimens.

OBJECTIVES: To examine immune restoration in duodenal tissue and correlates of reduction of immune activation in chronic HIV-infected patients randomized to different treatment regimens. DESIGN: Randomized clinical trial (RCT) comparing raltegravir to a non-nucleoside reverse transcriptase inhibitor-based regimen, both with fixed-dose tenofovir difumerate/emtricitabine. METHODS: Antiretroviral therapy (ART)-naive volunteers underwent upper endoscopy for duodenal biopsies before and after 9 months of therapy. Tissue was paraffin-embedded for immunohistochemistry or digested into single-cell suspensions for flow cytometry of lymphocyte subsets and activation phenotype. Plasma-soluble CD14 levels were measured as a surrogate for bacterial translocation. RESULTS: Sixteen HIV-positive and seven control individuals completed study procedures. Small increases in duodenal lamina propria CD4 T-cell numbers were observed, especially when viewed relative to populations in control volunteers, with no differences between treatment arms. The increase in CD4 T-cell percentage was due largely to declines in CD8 T-cell numbers, which were disproportionately increased compared to peripheral blood and controls. Patients randomized to the raltegravir arm had consistent declines in both sCD14 levels and CD8 T-cell numbers in the duodenal tissue lamina propria. CONCLUSIONS: This first RCT of lymphocyte population restoration in duodenal tissue demonstrates more modest increases in CD4 T-cell numbers during the first 9 months of therapy than when considering CD3/CD4 percentages only. Although reduced after 9 months of ART, disproportional increased CD8 populations persist in duodenal gastrointestinal-associated lymphoid tissue (GALT). Local rather than systemic antigenic stimulation appears to be driving expanded CD8 T lymphocytes in GALT. Factors other than viral-induced CD8 expansion may be contributing to this local immunologic response.

S-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, randomized, placebo-controlled trial.

BACKGROUND: S-adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and regulates the synthesis of glutathione, the main cellular antioxidant. Previous experimental studies suggested that SAM may benefit patients with established alcoholic liver diseases (ALDs). The aim of this study was to determine the efficacy of SAM in treatment for ALD in a 24-week trial. The primary endpoints were changes in serum aminotransferase levels and liver histopathology scores, and the secondary endpoints were changes in serum levels of methionine metabolites. METHODS: We randomized 37 patients with ALD to receive 1.2 g of SAM by mouth or placebo daily. Subjects were required to remain abstinent from alcohol drinking. A baseline liver biopsy was performed in 24 subjects, and a posttreatment liver biopsy was performed in 14 subjects. RESULTS: Fasting serum SAM levels were increased over timed intervals in the SAM treatment group. The entire cohort showed an overall improvement of AST, ALT, and bilirubin levels after 24 weeks of treatment, but there were no differences between the treatment groups in any clinical or biochemical parameters nor any intra- or intergroup differences or changes in liver histopathology scores for steatosis, inflammation, fibrosis, and Mallory-Denk hyaline bodies. CONCLUSIONS: Whereas abstinence improved liver function, 24 weeks of therapy with SAM was no more effective than placebo in the treatment for ALD.

Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation.

BACKGROUND: The relationship between gut microbial community composition at the higher-taxonomic order level and local and systemic immunologic abnormalities in HIV disease may provide insight into how bacterial translocation impacts HIV disease. METHODS: Antiretroviral-naive patients with HIV underwent upper endoscopy before and 9 months after starting antiretroviral treatment. Duodenal tissue was paraffin-embedded for immunohistochemical analysis and digested for fluorescence activated cell sorting for T-cell subsets and immune activation (CD38+/HLA-DR+) enumeration. Stool samples were provided from patients and control subjects for comparison. Metagenomic microbial DNA was extracted from feces for optimized 16S ribosomal RNA gene (rDNA) real-time quantitative polymerase chain reaction assays designed to quantify panbacterial loads and the relative abundances of proinflammatory Enterobacteriales order and the dominant Bacteroidales and Clostridiales orders. RESULTS: Samples from 10 HIV subjects before initiating and from six subjects receiving antiretroviral treatment were available for analysis. There was a trend for a greater proportion of Enterobacteriales in HIV-positive subjects compared with control subjects (P = 0.099). There were significant negative correlations between total bacterial load and duodenal CD4 and CD8 T-cell activation levels (r = -0.74, P = 0.004 and r = -0.67, P = 0.013, respectively). The proportions of Enterobacteriales and Bacteroidales were significantly correlated with duodenal CD4 T-cell depletion and peripheral CD8 T-cell activation, respectively. CONCLUSIONS: These data represent the first report of quantitative molecular and cellular correlations between total/universal and order-level gut bacterial populations and gastrointestinal-associated lymphoid tissue levels of immune activation in HIV-infected subjects. The correlations between lower overall 16S rDNA levels and tissue immune activation suggest that the gut microbiome may contribute to immune activation and influence HIV progression.

Markers of abuse liability of short- vs long-acting opioids in chronic pain patients: a randomized cross-over trial.

BACKGROUND: Abuse liability is thought to possibly be lower in long- than in short-acting opioids because lower peak serum levels may be less likely to induce psychoactive effects. METHODS: We compared patient responses to extended-release morphine, hydrocodone plus acetaminophen, and placebo in a randomized, double-blind crossover study using markers of abuse liability. Patients indicated their craving for drugs on 5 visual analog scales (VASs), completed the Addiction Research Center Inventory, and underwent cue reactivity testing. To perform the latter, subjects watched a video intended to produce a positive or a negative affect, after which a vial of medication was or was not presented (the cue) and then indicated their craving for drugs on 5 different VASs (the reactivity). RESULTS: Differences in Addiction Research Inventory scores were statistically significant but clinically unimportant. Neuropsychological test results were mixed and unrelated to the medications studied. Cue reactivity did not differ among conditions but was uniformly high. CONCLUSIONS: Using several markers of abuse liability, long-acting opioids do not have lower abuse potential than do short-acting opioids or placebo. Although cue reactivity did not differ among the conditions, uniformly high results in these patients suggest that it may have some value as a component of abuse liability testing.