The triple helix of clinical, research, and education missions in academic health centers: A qualitative study of diverse stakeholder perspectives.

INTRODUCTION: Academic health centers are poised to improve health through their clinical, education, and research missions. However, these missions often operate in silos. The authors explored stakeholder perspectives at diverse institutions to understand challenges and identify alignment strategies. METHODS: Authors used an exploratory qualitative design and thematic analysis approach with data obtained from electronic surveys sent to participants at five U.S. academic health centers (2017-18), with four different types of medical school/health system partnerships. Participants included educators, researchers, system leaders, administrators, clinical providers, resident/fellow physicians, and students. Investigators coded data using constant comparative analysis, met regularly to reconcile uncertainties, and collapsed/combined categories. RESULTS: Of 175 participants invited, 113 completed the survey (65%). Three results categories were identified. First, five higher-order themes emerged related to aligning missions, including (a) shared vision and strategies, (b) alignment of strategy with community needs, (c) tension of economic drivers, (d) coproduction of knowledge, and (e) unifying set of concepts spanning all missions. Second, strategies for each mission were identified, including education (new competencies, instructional methods, recruitment), research (shifting agenda, developing partnerships, operations), and clinical operations (delivery models, focus on patient factors/needs, value-based care, well-being). Lastly, strategies for integrating each dyadic mission pair, including research-education, clinical operations education, and research-clinical operations, were identified. CONCLUSIONS: Academic health centers are at a crossroads in regard to identity and alignment across the tripartite missions. The study's results provide pragmatic strategies to advance the tripartite missions and lead necessary change for improved patient health.

Exploiting the power of information in medical education.

The explosion of medical information demands a thorough reconsideration of medical education, including what we teach and assess, how we educate, and whom we educate. Physicians of the future will need to be self-aware, self-directed, resource-effective team players who can synthesize and apply summarized information and communicate clearly. Training in metacognition, data science, informatics, and artificial intelligence is needed. Education programs must shift focus from content delivery to providing students explicit scaffolding for future learning, such as the Master Adaptive Learner model. Additionally, educators should leverage informatics to improve the process of education and foster individualized, precision education. Finally, attributes of the successful physician of the future should inform adjustments in recruitment and admissions processes. This paper explores how member schools of the American Medical Association Accelerating Change in Medical Education Consortium adjusted all aspects of educational programming in acknowledgment of the rapid expansion of information.

Acute Liver Failure Requiring Liver Transplantation due to Acute Hepatitis A Virus Infection.

INTRODUCTION: Hepatitis A infection (HAV) is generally characterized by an acute icteric illness or may have a subclinical self-limited course, although rarely, can result in fulminant hepatitis and death. In 2019, the City of Philadelphia declared a public health emergency due to an HAV outbreak. We are reporting a series of four cases of acute liver failure (ALF) requiring liver transplantation (LT) due to acute HAV. METHODS: Chart review and case descriptions of four patients with acute HAV-related ALF who were expeditiously evaluated, listed as Status 1A, and who underwent LT between August 2019 and October 2019 at Thomas Jefferson University Hospital. RESULTS: All four patients presented with acute hepatocellular jaundice and had a positive HAV IgM, and all other causes of ALF were excluded. All four cases met the American Association for the Study of Liver Diseases (AASLD) criteria for ALF. Three of the four cases met King's College Criteria of poor prognosis for nonacetaminophen-induced ALF. All four patients underwent successful LT and were discharged six to twelve days postoperatively. One patient died of disseminated Aspergillus infection five months after LT, while the others have had excellent clinical outcomes shown by one-year follow-ups. All four explants had remarkably similar histological changes, revealing acute hepatitis with massive necrosis accompanied by a prominent lymphoplasmacytic inflammatory infiltrate and bile ductular proliferation. CONCLUSION: Although rare, patients presenting with acute HAV need close monitoring as they may rapidly progress to ALF. Early referral to a transplant center afforded timely access to LT and yielded overall good one-year survival. Widespread HAV vaccination for high-risk individuals is an essential strategy for preventing disease and curbing such future outbreaks.

Timely diagnosis and staging of non-alcoholic fatty liver disease using transient elastography and clinical parameters.

BACKGROUND AND AIM: There is no standardized guideline to screen, image, or refer patients with non-alcoholic fatty liver disease (NAFLD) to a specialist. In this study, we used transient elastography (TE) to examine the fibrosis stages at which patients are first diagnosed with NAFLD. Subsequently, we analyzed metabolic markers to establish cut-offs beyond which noninvasive imaging should be considered to confirm NAFLD/non-alcoholic steatohepatitis fibrosis in patients. METHODS: Charts spanning July 2015-April 2018 for 116 NAFLD patients who had TE performed were reviewed. Univariate and multivariate analysis of metabolic markers was conducted. RESULTS: At the first hepatology visit, TE showed 73% F0-F2 and 27% F3-F4. Univariate analysis showed that high-density lipoproteins (HDL), hemoglobin A1c (A1c), aspartate transaminase (AST), and alanine transaminase (ALT) were significantly different between the F0-F2 and F3-F4 groups. Multivariate analysis showed that AST (P = 0.01) and A1c (P = 0.05) were significantly different. Optimal cut-offs for these markers to detect liver fibrosis on TE were AST >43 U/L and A1c >6.6%. The logistic regression function combining these two variables to reflect the probability (P) of the patient having advanced fibrosis (F3-F4) on TE yielded the formula: P = e R /(1 + e R ), where R = -8.56 + 0.052 * AST + 0.89 * A1c. CONCLUSIONS: Our study suggested that >25% of patients presenting to a specialist for NAFLD may have advanced fibrosis (F3-F4). Diabetes (A1c >6.6%) and AST >43 U/L were the most predictive in identifying NAFLD patients with advanced fibrosis on imaging. We proposed a formula that may be used to prioritize NAFLD patients at higher risk of having advanced fibrosis for specialist referral and imaging follow-up.

A Rare Case of Wilson Disease in a 72-Year-Old Patient.

Wilson disease is an autosomal recessive disorder of abnormal copper metabolism that is prevalent in the younger population, rarely presenting in patients older than 40 years. Clinical presentation may be variable, and diagnosis is often aided by clinical and biochemical tests. We report the case of a 72-year-old woman who presented with acute liver failure initially of unclear etiology. Our patient was initially managed for presumed drug-induced liver injury but ultimately diagnosed with Wilson disease on the basis of clinical presentation, laboratory testing, liver biopsy, quantitative hepatic copper, and abnormal genetic testing.

The Time Is Now for Mandatory Liver-Focused Clinical Experiences in Medical School.

The national burden of chronic liver disease is steadily increasing and is only expected to worsen with the ongoing obesity and opioid epidemics fueling growth in the prevalence of nonalcoholic fatty liver disease and a resurgence of new hepatitis C infections. Our letter highlights the disparity between the rising prevalence of chronic liver disease and the proportion of medical students who receive exposure to patients with liver disease as part of their medical education. A more comprehensive survey of clerkship directors is needed to further corroborate this data, which may lead to reforms in medical school curricula to better address the expanding burden of chronic liver disease.

The Archetypes of Medicine: A Job Description for the 21st Century.

Medicine is facing an identity crisis, one that might find resolution by revisiting a past rich in multifaceted individuals who transcended the strict definition of 'doctor', excelled in other fields of human endeavor, and showed us different ways of being physicians. This paper reviews 12 archetypes that have been part of the profession since its inception, but that, as of late, might have been forgotten. Our goal is to elicit discussion and introspection, with the premise that being a physician ought to be something larger than being a mere technician. If our premise is accepted, then the next step would be to identify those personal traits that made those archetypes possible, so that we can start both recruiting for them and then nurturing them during training.

Obstetricians' and gynecologists' knowledge, education, and practices regarding chronic hepatitis B in pregnancy.

BACKGROUND: In pregnant women with high viral loads, third-trimester initiation of antiviral agents can reduce the risk of vertical transmission. We aimed to assess obstetricians' and gynecologists' (OB-GYN) knowledge and clinical practice when treating pregnant women with chronic hepatitis B virus (HBV). METHODS: All program directors (PDs) from 250 US OB-GYN residency programs were invited to anonymously complete an 18-item questionnaire. Descriptive statistics were calculated and analyzed. RESULTS: A total of 323 participants responded, including both PDs (n=51, response rate 21%) and residents (n=272, response rate 11%). Responding PDs (62% university-based vs. 32% community-based) came from various practice types. All PDs and 95.2% of residents reported screening for chronic HBV in pregnant patients on the first prenatal visit. A majority of PDs (85.5%) and residents (85%) correctly interpreted HBV serologies. Referral patterns showed that 66.7% of PDs and 65.5% of residents refer to a specialist regardless of viral load. A minority of respondents (19.6% PDs and 12.6% residents) knew that third-trimester antiviral therapy is recommended for women with high viral loads (>200,000 IU/mL). Few respondents had prescribed HBV antivirals (9.8% PDs and 6.0% residents), with residents more commonly prescribing tenofovir and less frequently lamivudine. Half the PDs believed trainees from their programs were comfortable managing HBV in pregnancy, but only 41.8% of residents reported being comfortable managing pregnant patients with HBV. CONCLUSION: OB-GYNs report screening almost all pregnant patients for chronic HBV, though significant gaps still exist in practitioner comfort and training regarding the management of HBV during pregnancy.

Hepatocellular carcinoma after locoregional therapy: Magnetic resonance imaging findings in falsely negative exams.

AIM: To elucidate causes for false negative magnetic resonance imaging (MRI) exams by identifying imaging characteristics that predict viable hepatocellular carcinoma (HCC) in lesions previously treated with locoregional therapy when obvious findings of recurrence are absent. METHODS: This retrospective institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study included patients who underwent liver transplantation at our center between 1/1/2000 and 12/31/2012 after being treated for HCC with locoregional therapy. All selected patients had a contrast-enhanced MRI after locoregional therapy within 90 d of transplant that was prospectively interpreted as without evidence of residual or recurrent tumor. Retrospectively, 2 radiologists, blinded to clinical and pathological data, independently reviewed the pre-transplant MRIs for 7 imaging features. Liver explant histopathology provided the reference standard, with clinically significant tumor defined as viable tumor ≥ 1.0 cm in maximum dimension. Fisher's exact test was first performed to identify significant imaging features. RESULTS: Inclusion criteria selected for 42 patients with 65 treated lesions. Fourteen of 42 patients (33%) and 16 of 65 treated lesions (25%) had clinically significant viable tumor on explant histology. None of the 7 imaging findings examined could reliably and reproducibly determine which treated lesion had viable tumor when the exam had been prospectively read as without evidence of viable HCC. CONCLUSION: After locoregional therapy some treated lesions that do not demonstrate any MRI evidence of HCC will contain viable tumor. As such even patients with a negative MRI following treatment should receive regular short-term imaging surveillance because some have occult viable tumor. The possibility of occult tumor should be a consideration when contemplating any action which might delay liver transplant.

A Clinical Decision Rule Based on the AST-to-Platelet Ratio Index Improves Adherence to Published Guidelines on the Management of Acute Variceal Bleeding.

BACKGROUND: Optimal management of acute upper gastrointestinal bleeding (UGIB) depends on identifying a variceal versus nonvariceal etiology. An objective measure predicting etiology could guide early management pending endoscopy. The AST-to-platelet ratio index (APRI) score has been studied as a marker of cirrhosis and portal hypertension, but has not been evaluated in the setting of acute UGIB. METHODS: In this single-center retrospective cohort study, we reviewed endoscopy reports and other data for patients with acute UGIB, and classified episodes as variceal bleeds or other. We assessed the diagnostic utility of the APRI score relative to other objective measures by Area Under the Receiver Operating Characteristic (AUROC) curve analysis. We constructed a clinical decision rule based on the APRI score, and assessed how it would have changed management. RESULTS: The APRI score performed well in predicting a variceal etiology of acute UGIB, with AUROC 0.89. We developed a clinical decision rule using an APRI score of 0.4 to guide early management of acute UGIB patients. Retroactively applying this to our cohort, adherence to published guidelines for administration of octreotide and antibiotics would have increased from 56% to 91%. CONCLUSIONS: The APRI score is an objective metric that helps predict a variceal etiology of acute UGIB. Using our proposed decision rule could improve adherence to guidelines on management of acute variceal bleeding. Although we were unable to demonstrate a survival benefit, improved adherence to evidence-based guidelines serves as a metric related to this most important outcome measure. Prospective study to validate these findings is indicated.

Training directors have positive perceptions of a competency-based gastroenterology and transplant hepatology fellowship program.

BACKGROUND & AIMS: In 2012, the American Board of Internal Medicine approved a pilot competency-based transplant hepatology (TH) training program. This program allows gastroenterology (GI) and TH fellowships to be completed in 3 years. We investigated the perceptions and beliefs of GI and TH division and fellowship program directors on the competency-based TH training program. METHODS: All current GI and TH division and fellowship program directors from the 162 fellowship programs accredited by the Accreditation Council for Graduate Medical Education were invited via e-mail to anonymously complete the online survey. The survey questioned their perceptions of the 3-year combined GI and TH training program. RESULTS: A total of 116 participants completed the survey (∼38% response rate). Most respondents were GI fellowship directors (61%); 15% were GI and hepatology division directors, 19% were TH fellowship directors, 14% were TH division directors, and 5% were GI division directors. Most of the respondents were in favor of the pilot program (85%). Only 63% of all respondents believed that graduates of the pilot program would achieve the same level of competency in GI as those who completed the traditional program. Overall, 71% believed incorporation of the 3-year training model would increase interest and participation in TH fellowships. CONCLUSIONS: Most of the academic GI and TH division and fellowship program directors embrace competency-based fellowship education and TH subspecialty training during the designated 3-year GI fellowship. Future studies will be needed to reevaluate these beliefs after several years.

Patterns of acetaminophen use exceeding 4 grams daily in a hospitalized population at a tertiary care center.

Unintentional acetaminophen-induced hepatotoxicity has been increasingly recognized as a significant problem, prompting increased scrutiny and restrictions from the US Food and Drug Administration on products combining acetaminophen with narcotics. Patterns of acetaminophen use have not previously been reported in the hospitalized patient population, which may be especially vulnerable to liver injury. We aimed to quantify the frequency at which acetaminophen dosing exceeded the recommended maximum of 4 g/day in hospitalized patients. This was a retrospective, single-center, cohort study at a large tertiary care academic hospital. We queried our inpatient electronic medical record database to identify patients admitted between 2008 and 2010 who were receiving cumulative daily acetaminophen doses exceeding 4 g on at least 1 hospital day. Of 43,761 admissions involving acetaminophen administration, the recommended maximum cumulative daily dose of 4 g was exceeded in 1119 (2.6%) cases. Patients who were administered a larger number of acetaminophen-containing medications were more likely to receive doses in excess of the recommended maximum. Alanine aminotransferase (ALT) levels were checked within 14 days following acetaminophen exposure in excess of 4 g in 35 (3.1%) cases. Excessive acetaminophen dosing of hospitalized patients, who may be at increased risk for acetaminophen-induced hepatotoxicity, occurred in a minority of patients. The use of multiple acetaminophen-containing medication formulations contributed to excessive dosing. ALT level monitoring in this group was infrequent, precluding assessment of biochemical evidence of liver injury. This cohort of patients may represent an ideal population for further prospective study with more intensive and longer-term biochemical monitoring to assess for evidence of liver injury.

Occupational exposure to hepatitis C virus: early T-cell responses in the absence of seroconversion in a longitudinal cohort study.

BACKGROUND: T-cell responses have been described in seronegative patients who test negative for hepatitis C virus (HCV) RNA despite frequent HCV exposure. However, the cross-sectional design of those studies did not clarify whether T cells were indeed induced by low-level HCV exposure without seroconversion or whether they resulted from regular acute infection with subsequent antibody loss. METHODS: Over a 10-year period, our longitudinal study recruited 72 healthcare workers with documented HCV exposure. We studied viremia and antibody and T-cell responses longitudinally for 6 months. RESULTS: All healthcare workers remained negative for HCV RNA and antibodies. However, 48% developed proliferative T-cell response and 42% developed responses in interferon-gamma enzyme-linked immunosorbent spot assays, with 29 healthy HCV-unexposed controls used to define assay cutoffs. The response prevalence was associated with the transmission risk score. T-cell responses peaked at week 4 and returned to baseline by week 12 after exposure. They predominantly targeted nonstructural HCV proteins, which are not part of the HCV particle and thus must have been synthesized in infected cells. CONCLUSIONS: Subclinical transmission of HCV occurs frequently, resulting in infection and synthesis of nonstructural proteins despite undetectable systemic viremia. T-cell responses are more sensitive indicators of this low-level HCV exposure than antibodies.

Single-center comparison of three chemoembolization regimens for hepatocellular carcinoma.

PURPOSE: Transarterial chemoembolization regimens for hepatocellular carcinoma (HCC) vary, without a gold-standard method. The present study was performed to evaluate outcomes in patients with HCC treated with doxorubicin/ethiodized oil (DE), cisplatin/doxorubicin/mitomycin-c/ethiodized oil (CDM), or doxorubicin drug-eluting beads (DEBs). MATERIALS AND METHODS: Patients received the same regimen at all visits, without crossover. Groups were compared based on Child-Pugh disease status, tumor/node/metastasis stage, and Barcelona Clinic Liver Cancer stage. Imaging outcomes were assessed based on modified Response Evaluation Criteria in Solid Tumors to calculate tumor response (ie, sum of complete and partial response), progressive disease (PD), and time to progression (TTP). RESULTS: A total of 228 infusions were performed in 122 patients: 59 with DE, 30 with CDM, and 33 with DEBs. The groups had similar Child-Pugh status (P = .45), tumor/node/metastasis stages (P = .5), and Barcelona Clinic Liver Cancer scores (P = .22). Follow-up duration was similar among groups (P = .24). Patients treated with DE underwent significantly more treatments (2.3 ± 1.4) than those treated with CDM (1.6 ± 0.7; P = .004) or DEBs (1.4 ± 0.6; P<.0001). Compared with DE (51%), tumor response was significantly more common with CDM (84%; P = .003) or DEBs (82%; P = .004). PD was significantly more likely with DE (37%) than with CDM (13%; P = .02) or DEBs (9%; P = .004). TTP was similar between groups (P = .07). CDM and DEBs were similar in regard to disease progression (P = .6) and response (P = .83). CONCLUSIONS: During a similar follow-up period, patients treated with CDM or DEB chemoembolization showed a significantly higher response rate and a lower incidence of tumor progression, with fewer required treatment sessions, than those treated with DE chemoembolization.

Racial differences in hepatitis C treatment eligibility.

UNLABELLED: Black Americans are disproportionally infected with hepatitis C virus (HCV) and are less likely than whites to respond to treatment with peginterferon (PEG-IFN) plus ribavirin (RBV). The impact of race on HCV treatment eligibility is unknown. We therefore performed a retrospective analysis of a phase 3B multicenter clinical trial conducted at 118 United States community and academic medical centers to evaluate the rates of and reasons for HCV treatment ineligibility according to self-reported race. In all, 4,469 patients were screened, of whom 1,038 (23.2%) were treatment ineligible. Although blacks represented 19% of treated patients, they were more likely not to be treated due to ineligibility and/or failure to complete required evaluations (40.2%) than were nonblack patients (28.5%; P < 0.001). After the exclusion of persons not treated due to undetectable HCV RNA or nongenotype 1 infection, blacks were 65% less likely than nonblacks to be eligible for treatment (28.1% > 17.0%; relative risk, 1.65; 95% confidence interval, 1.46-1.87; P < 0.001). Blacks were more likely to be ineligible due to neutropenia (14% versus 3%, P < 0.001), anemia (7% versus 4%, P = 0.02), elevated glucose (8% versus 3%, P < 0.001), and elevated creatinine (5% versus 1%, P < 0.001). CONCLUSION: Largely due to a higher prevalence of neutropenia and uncontrolled medical conditions, blacks were significantly less likely to be eligible for HCV treatment. Increased access to treatment may be facilitated by less conservative neutrophil requirements and more effective care for chronic diseases, namely, diabetes and renal insufficiency.

Hepatitis C virus treatment-related anemia is associated with higher sustained virologic response rate.

BACKGROUND & AIMS: Hepatitis C virus (HCV) treatment is frequently complicated by anemia from ribavirin (RBV)-related hemolysis and peginterferon-alfa (PEG-IFN)-related bone marrow suppression. We investigated the relationships among treatment outcomes, anemia, and their management with RBV dose reduction and/or erythropoiesis-stimulating agents (ESAs). METHODS: We analyzed data from a trial conducted at 118 United States academic and community centers in treatment-naïve patients with HCV genotype 1. Patients were treated for as many as 48 weeks with 1 of 3 PEG-IFN/RBV regimens. ESAs were permitted for anemic patients (hemoglobin [Hb] <10 g/dL) after RBV dose reduction. Sustained virologic responses (SVR) were assessed based on decreases in Hb, anemia, and ESA use. RESULTS: While patients received treatment, 3023 had their Hb levels measured at least once. An SVR was associated with the magnitude of Hb decrease: >3 g/dL, 43.7%; ≤3 g/dL, 29.9% (P < .001). Anemia occurred in 865 patients (28.6%); 449 of these (51.9%) used ESAs. In patients with early-onset anemia (≤ 8 weeks of treatment), ESAs were associated with higher SVR rate (45.0% vs 25.9%; P < .001) and reduced discontinuation of treatment because of adverse events (12.6% vs 30.1%, P < .001). ESAs did not affect SVR or discontinuation rates among patients with late-stage anemia. CONCLUSIONS: Among HCV genotype 1-infected patients treated with PEG-IFN/RBV, anemia was associated with higher rates of SVR. The effect of ESAs varied by time to anemia; patients with early-onset anemia had higher rates of SVR with ESA use, whereas no effect was observed in those with late-onset anemia. Prospective trials are needed to assess the role of ESAs in HCV treatment.