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.

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.

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.

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.

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.

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.

Over-the-counter analgesics in cirrhotic patients: a case-control study examining the risk of hospitalization for liver-associated events.

OBJECTIVE: To assess the association between over-the-counter analgesic (OTCA) use and hospitalization for liver-associated events in cirrhotic patients. MATERIAL AND METHODS: Ninety adult cirrhotics admitted with liver-associated events and 126 non-hospitalized cirrhotic controls were enrolled prospectively into a case-control study. Standardized questionnaires were used to obtain predictor variables, including detailed 30-day OTCA use. Data were analyzed via logistic regression. RESULTS: Hepatitis C (43%), alcohol (34%), and cryptogenic (13%) were the most common etiologies of cirrhosis. OTCA use was similar between cases and controls in the 30 days prior to enrollment (34% vs. 44%; odds ratio, OR = 0.66, 95% confidence interval, CI = 0.37-1.16, p = 0.148). Adjusted analyses also found no significant association between OTCA use and hospitalization for liver-associated events (OR = 0.73, 95% CI = 0.38-1.38, p = 0.330). Furosemide (p = 0.001), lactulose (p = 0.026), and number of prior liver-associated events (p = 0.002) were positively associated with hospitalization, while propranolol showed an inverse association (p = 0.008). CONCLUSION: Our data suggest that non-excessive OTCA use is not significantly associated with hospitalization for liver-associated events.

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.

Serologic markers do not predict histologic severity or response to treatment in patients with autoimmune hepatitis.

BACKGROUND & AIMS: Autoimmune hepatitis (AIH) is characterized by the presence of circulating autoantibodies, hypergammaglobulinemia, necroinflammatory histology, and a response to immunosuppressive drugs. The goal of this retrospective study was to determine whether the presence of antinuclear antibodies (ANAs) or anti-smooth muscle antibodies (ASMAs) in patients with AIH correlated with clinical presentation, histologic findings, or response to immunosuppressive therapy. METHODS: Fifty-two patients diagnosed with AIH, on the basis of the revised scoring system of International Autoimmune Hepatitis group, were reviewed. Data on age, gender, aminotransferase levels, autoantibody titers, treatment regimens, and response to treatment were recorded. Seropositivity was defined as ANA >1:40 or ASMA >1:40. Percutaneous liver biopsies obtained at the initial presentation were reviewed. RESULTS: Forty-two patients with AIH (81%) were seropositive, and 10 (19%) were seronegative. Both groups were similar with respect to demographics, treatment regimens, and response to therapy. Histologic parameters were similar among the 2 groups, including portal and lobular inflammation, piecemeal necrosis, and centrilobular necrosis. There were no significant differences in aminotransferase levels at diagnosis or after treatment. CONCLUSIONS: The prevalence of ANAs or ASMAs did not correlate with the clinical or histologic severity of AIH at diagnosis. Furthermore, there was no correlation between antibody status and response to immunosuppressive therapy. Therefore, patients who meet the diagnosis of AIH on the basis of the revised scoring system of International Autoimmune Hepatitis Group should be given immunosuppressive therapy, regardless of antibody status.

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.

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.

Use of over-the-counter analgesics in patients with chronic liver disease: physicians' recommendations.

BACKGROUND: Over-the-counter analgesics (OTCAs), principally paracetamol (acetaminophen)-containing compounds and NSAIDs, are commonly used medications. Guidelines for the use of these agents in patients with chronic liver disease (CLD) are not available, despite the possibility that such patients may be more susceptible to the effects of an adverse reaction. Notwithstanding the lack of guidelines for healthcare providers, patients are often counselled to modify their use of these drugs. Therefore, the primary aim of this study was to assess healthcare providers' recommendations on how OTCAs should be used by patients with CLD. METHODS: An 11-question web-based survey was distributed via email to healthcare providers participating in four healthcare networks in the US, to determine what recommendations they make to patients with cirrhosis (compensated and decompensated) and chronic hepatitis regarding the use of paracetamol and NSAIDs. Healthcare providers were also queried about the recommendations they make to patients with cirrhosis regarding pain control, and on the use of paracetamol for patients who consume alcohol daily. RESULTS: Overall, a 12% response rate was obtained. Internal medicine, family practice, paediatrics, and gastroenterology were the most represented practice types. Recommendations against the use of NSAIDs were significantly less common than recommendations against paracetamol use, in cases of both compensated and decompensated cirrhosis (p = 0.001). Non-gastroenterologists and non-primary care physicians were the least likely to recommend against NSAID use (p = 0.001), while gastroenterologists were the least likely to recommend against paracetamol in these patients (p = 0.001). It was the recommendation of most respondents that OTCAs should be avoided in patients with cirrhosis, and that paracetamol should be avoided or its dose reduced in the setting of daily alcohol use. CONCLUSIONS: Significant variability exists among healthcare providers on their recommendations for OTCA use in the setting of chronic liver disease. Non-gastroenterologists are more likely to recommend against the use of paracetamol than NSAIDs, and patients with chronic liver disease may be under-treated for pain.

Compensated hepatitis C: unenhanced MR imaging correlated with pathologic grading and staging.

BACKGROUND: We prospectively examined unenhanced MR imaging findings in relation to pathologic fibrosis, inflammation and steatosis in patients with compensated chronic hepatitis C viral infection (HCV). METHODS: Unenhanced MRI at 1.5 T was obtained within one month of core liver biopsy in 64 consecutive candidates for antiviral therapy for compensated HCV. Two pathologists independently graded inflammatory activity index (HAI) and steatosis, and staged fibrosis (grades 0-6). Morphologic MRI findings of cirrhosis, periportal lymph nodes, and MR fat signal ratio from dual gradient echo images were assessed independently by two radiologists blinded to clinical data. MRI and laboratory liver function results were correlated with pathologic results, using Spearman correlation coefficient and stepwise multiple regression. RESULTS: MR fat signal ratio correlation coefficient with pathologic steatosis was 0.71 (p < 0.0001). Coefficients with fibrosis stage were highest for surface nodularity (r (s) = 47, p < 0.0001) and expanded gallbladder fossa (r (s) = 0.42, p = 0.0006). Coefficients with HAI were highest for lymph node size (r (s) = 0.355, p = 0.0040), surface nodularity (r = 0.47, p < 0.0001), expanded gallbladder fossa (r = 0.332, p = 0.0073), and caudate/right lobe ratio (r = 0.326, p = 0.0110). Combined lab and MRI variables provided the best prediction of fibrosis stage (r (2) = 0.656) and HAI (r (2) = 0.597). CONCLUSIONS: A combination of MRI and laboratory findings was most predictive of fibrosis and inflammation.

Hepatitis C risk assessment, testing and referral for treatment in urban primary care: role of race and ethnicity.

AIM: To determine rates of hepatitis C (HCV) risk factor ascertainment, testing, and referral in urban primary care practices, with particular attention to the effect of race and ethnicity. METHODS: Retrospective chart review from four primary care sites in Philadelphia; two academic primary care practices and two community clinics was performed. Demographics, HCV risk factors, and other risk exposure information were collected. RESULTS: Four thousand four hundred and seven charts were reviewed. Providers documented histories of injection drug use (IDU) and transfusion for less than 20% and 5% of patients, respectively. Only 55% of patients who admitted IDU were tested for HCV. Overall, minorities were more likely to have information regarding a risk factor documented than their white counterparts (79% vs 68%, P < 0.0001). Hispanics were less likely to have a risk factor history documented, compared to blacks and whites (P < 0.0001). Overall, minorities were less likely to be tested for HCV than whites in the presence of a known risk factor (23% vs 35%, P = 0.004). Among patients without documentation of risk factors, blacks and Hispanics were more likely to be tested than whites (20% and 24%, vs 13%, P < 0.005, respectively). CONCLUSION: (1) Documentation of an HCV risk factor history in urban primary care is uncommon, (2) Racial differences exist with respect to HCV risk factor ascertainment and testing, (3) Minority patients, positive for HCV, are less likely to be referred for subspecialty care and treatment. Overall, minorities are less likely to be tested for HCV than whites in the presence of a known risk factor.