Faculty Bibliography

BACKGROUND:Multidrug-resistant Enterobacterales (MDR-E), including carbapenem-resistant and third-generation cephalosporin-resistant Enterobacterales (CRE, CefR-E), are major pathogens following solid organ transplantation (SOT). METHODS:We prospectively studied patients who underwent lung, liver and small bowel transplant from February 2015-March 2017. Weekly peri-rectal swabs (up to 100 days post-transplant) were cultured for MDR-E. Whole genome sequencing (WGS) was performed on gastrointestinal (GI) tract-colonizing and disease-causing isolates. RESULTS:Twenty-five percent (40/162) of patients were MDR-E GI-colonized. Klebsiella pneumoniae was the most common CRE and CefR-E. K. pneumoniae carbapenemases and CTX-M were leading causes of CR and CefR, respectively. Thirty-five percent of GI-colonizers developed MDR-E infection versus 2% of non-colonizers (p<0.0001). Attack rate was higher among CRE colonizers than CefR-E colonizers (53% versus 21%, p=0.049). GI-colonization and high body mass index were independent risk factors for MDR-E infection (p≤0.004). Thirty-day mortality among infected patients was 6%. However, 44% of survivors developed recurrent infections; 43% of recurrences were late (285 days-3.9 years post-initial infection). Long-term survival (median: 4.3 years post-transplant) did not differ significantly between MDR-E-infected and non-infected patients (71% versus 77%, p=0.56). WGS phylogenetic analyses revealed that infections were caused by GI-colonizing strains, and suggested unrecognized transmission of novel clonal group-258 sublineage CR-K. pneumoniae and horizontal transfer of resistance genes. CONCLUSIONS:MDR-E GI-colonization was common following SOT, and predisposed patients to infections by colonizing strains. MDR-E infections were associated with low short- and long-term mortality, but recurrences were frequent and often occurred years after initial infections. Findings provide support for MDR-E surveillance in our SOT program.

BACKGROUND:Statistically significantly increased cancer incidence has been reported from 3 cohorts of World Trade Center (WTC) disaster rescue and recovery workers. We pooled data across these cohorts to address ongoing public concerns regarding cancer risk 14 years after WTC exposure. METHODS:From a combined deduplicated cohort of 69 102 WTC rescue and recovery workers, a sample of 57 402 workers enrolled before 2009 and followed through 2015 was studied. Invasive cancers diagnosed in 2002-2015 were identified from 13 state cancer registries. Standardized incidence ratios (SIRs) were used to assess cancer incidence. Adjusted hazard ratios (aHRs) were estimated from Cox regression to examine associations between WTC exposures and cancer risk. RESULTS:Of the 3611 incident cancers identified, 3236 were reported as first-time primary (FP) cancers, with an accumulated 649 724 and 624 620 person-years of follow-up, respectively. Incidence for combined FP cancers was below expectation (SIR = 0.96, 95% confidence interval [CI] = 0.93 to 0.99). Statistically significantly elevated SIRs were observed for melanoma-skin (SIR = 1.43, 95% CI = 1.24 to 1.64), prostate (SIR = 1.19, 95% CI = 1.11 to 1.26), thyroid (SIR = 1.81, 95% CI = 1.57 to 2.09), and tonsil (SIR = 1.40, 95% CI = 1.00 to 1.91) cancer. Those arriving on September 11 had statistically significantly higher aHRs than those arriving after September 17, 2001, for prostate (aHR = 1.61, 95% CI = 1.33 to 1.95) and thyroid (aHR = 1.77, 95% CI = 1.11 to 2.81) cancers, with a statistically significant exposure-response trend for both. CONCLUSIONS:In the largest cohort of 9/11 rescue and recovery workers ever studied, overall cancer incidence was lower than expected, and intensity of WTC exposure was associated with increased risk for specific cancer sites, demonstrating the value of long-term follow-up studies after environmental disasters.

Importance/UNASSIGNED:There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective/UNASSIGNED:To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, Setting, and Participants/UNASSIGNED:CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions/UNASSIGNED:A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures/UNASSIGNED:The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results/UNASSIGNED:Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06). Conclusions and Relevance/UNASSIGNED:In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04364737.

Once medical students attain a certain level of medical knowledge, success in residency often depends on noncognitive attributes, such as conscientiousness, empathy, and grit. These traits are significantly more difficult to assess than cognitive performance, creating a potential gap in measurement. Despite its promise, competency-based medical education (CBME) has yet to bridge this gap, partly due to a lack of well-defined noncognitive observable behaviors that assessors and educators can use in formative and summative assessment. As a result, typical undergraduate to graduate medical education handovers stress standardized test scores, and program directors trust little of the remaining information they receive, sometimes turning to third-party companies to better describe potential residency candidates. The authors have created a list of noncognitive attributes, with associated definitions and noncognitive skills-called observable practice activities (OPAs)-written for learners across the continuum to help educators collect assessment data that can be turned into valuable information. OPAs are discrete work-based assessment elements collected over time and mapped to larger structures, such as milestones, entrustable professional activities, or competencies, to create learning trajectories for formative and summative decisions. Medical schools and graduate medical education programs could adapt these OPAs or determine ways to create new ones specific to their own contexts. Once OPAs are created, programs will have to find effective ways to assess them, interpret the data, determine consequence validity, and communicate information to learners and institutions. The authors discuss the need for culture change surrounding assessment-even for the adoption of behavior-based tools such as OPAs-including grounding the work in a growth mindset and the broad underpinnings of CBME. Ultimately, improving assessment of noncognitive capacity should benefit learners, schools, programs, and most importantly, patients.

BACKGROUND:It is not yet known whether socioeconomic factors (ie, social determinants of health) are associated with readmission following hospitalization for coronavirus disease 2019 (COVID-19). METHODS:We conducted a retrospective cohort study of 6191 adult patients hospitalized with COVID-19 in a large New York City safety-net hospital system between March 1 and June 1, 2020. Associations between 30-day readmission and selected demographic characteristics, socioeconomic factors, prior health care utilization, and relevant features of the index hospitalization were analyzed using a multivariable generalized estimating equation model. RESULTS:The readmission rate was 7.3%, with a median of 7 days between discharge and readmission. The following were risk factors for readmission: age 65 and older [adjusted odds ratio (aOR): 1.32; 95% confidence interval (CI): 1.13-1.55], history of homelessness, (aOR: 2.03 95% CI: 1.49-2.77), baseline coronary artery disease (aOR: 1.68; 95% CI: 1.34-2.10), congestive heart failure (aOR: 1.34; 95% CI: 1.20-1.49), cancer (aOR: 1.68; 95% CI: 1.26-2.24), chronic kidney disease (aOR: 1.74; 95% CI: 1.46-2.07). Patients' sex, race/ethnicity, insurance, and presence of obesity were not associated with increased odds of readmission. A longer length of stay (aOR: 0.98; 95% CI: 0.97-1.00) and use of noninvasive supplemental oxygen (aOR: 0.68; 95% CI: 0.56-0.83) was associated with lower odds of readmission. Upon readmission, 18.4% of patients required intensive care, and 13.7% expired. CONCLUSION:We have found some factors associated with increased odds of readmission among patients hospitalized with COVID-19. Awareness of these risk factors, including patients' social determinants of health, may ultimately help to reduce readmission rates.

PROBLEM/OBJECTIVE:Internal medicine training programs operate under the assumption that the three-year residency training period is sufficient for trainees to achieve the depth and breadth of clinical experience necessary for independent practice; however, the medical conditions to which residents are exposed in clinical practice are not easily measured. As a result, residents' clinical educational experiences are poorly understood. APPROACH/METHODS:A crosswalk tool (a repository of international classification of diseases [ICD]-10 codes linked to medical content areas) was developed to query routinely collected inpatient principal diagnosis codes and translate them into an educationally meaningful taxonomy. This tool provides a robust characterization of residents' inpatient clinical experiences. OUTCOMES/RESULTS:This pilot study has provided proof of principle that the crosswalk tool can effectively map one year of resident-attributed diagnosis codes to both the broad content category level (for example "Cardiovascular Disease") and to the more specific condition category level (for example "Myocardial Disease"). The authors uncovered content areas in their training program that are overrepresented and some that are underrepresented relative to material on the American Board of Internal Medicine (ABIM) Certification Exam. NEXT STEPS/UNASSIGNED:The crosswalk tool introduced here translated residents' patient care activities into discrete, measurable educational content and enabled one internal medicine residency training program to characterize residents' inpatient educational experience with a high degree of resolution. Leaders of other programs seeking to profile the clinical exposure of their trainees may adopt this strategy. Such clinical content mapping drives innovation in the experiential curriculum, enables comparison across practice sites, and lays the groundwork to test associations between individual clinical exposure and competency-based outcomes, which, in turn, will allow medical educators to draw conclusions regarding how clinical experience reflects clinical competency.

Patients with diabetes mellitus are at increased risk of cardiovascular events. We aimed to analyze the impact of serum HbA1c levels on coronary plaque characteristics in stable coronary disease. Two hundred sixty-one patients who underwent optical coherence tomography (OCT) examination before elective percutaneous coronary intervention for a de novo obstructive lesions were included in this single-center retrospective analysis. Patients were divided into tertiles according to HbA1c level (tertile 1: HbA1c < 6.3%, tertile 2: 6.3 ≤ HbA1c < 7.8%, tertile 3: HbA1c ≥ 7.8%) and OCT findings were compared. Fibrous cap thickness (FCT) was significantly thinner in tertile 3 compared to tertile 1 and tertile 2 (103.9 ± 48.2 µm [tertile 1] vs. 107.5 ± 60.6 µm [tertile 2] vs. 86.2 ± 35.8 µm [tertile 3], p = 0.03). Higher prevalence of thin-cap fibroatheroma (TCFA) was observed in tertile 3 vs tertile 1 and tertile 2 (19.5% [tertile 1] vs. 19.5% [tertile 2] vs. 33.3% [tertile 3], p = 0.04). HbA1c inversely correlated with FCT (beta coefficient - 4.89, 95% confidence interval - 8.40 to - 1.39, p < 0.01). The logistic regression model revealed that the probability of having TCFA was positively associated with HbA1c with a small change in the range of low and medium HbA1c and a big change in the range of high HbA1c. Furthermore, minimal lumen area and reference lumen area were smaller in tertile 3. In patients with stable coronary disease, high serum HbA1c levels are associated with higher plaque burden and thinner FCT on OCT, while low and medium HbA1c levels result in similar plaque vulnerability.

PURPOSE/OBJECTIVE:Emergency department (ED) visits by patients with cancer frequently end in hospitalization. As concerns about ED and hospital crowding increase, observation unit care may be an important strategy to deliver safe and efficient treatment for eligible patients. In this investigation, we compared the prevalence and clinical characteristics of cancer patients who received observation unit care with those who were admitted to the hospital from the ED. METHODS:We performed a multicenter prospective cohort study of patients with cancer presenting to an ED affiliated with one of 18 hospitals of the Comprehensive Oncologic Emergency Research Network (CONCERN) between March 1, 2016 and January 30, 2017. We compared patient characteristics with the prevalence of observation unit care usage, hospital admission, and length of stay. RESULTS:Of 1,051 enrolled patients, 596 (56.7%) were admitted as inpatients, and 72 (6.9%) were placed in an observation unit. For patients admitted as inpatients, 23.7% had a length of stay ≤2 days. The conversion rate from observation to inpatient was 17.1% (95% CI 14.6-19.4) among those receiving care in an observation unit. The average observation unit length of stay was 14.7 hours. Patient factors associated ED disposition to observation unit care were female gender and low Charlson Comorbidity Index. CONCLUSION/CONCLUSIONS:In this multicenter prospective cohort study, the discrepancy between observation unit care use and short inpatient hospitalization may represent underutilization of this resource and a target for process change.

Rationale: Allergic and non-allergic adverse reactions (ARs) to Covid-19 vaccine (Cov19V) have been reported. Understanding the characteristics of Cov19V ARs, particularly those that are allergic in nature, may help us to better counsel patients who are at risk of developing a vaccine AR.
Method(s): We performed a retrospective chart review of ARs voluntarily reported to our Occupational Health Services following Cov19V at a multi-site academic medical center between December 2020-June 2021.
Result(s): 464 Cov19V ARs among 71,281 vaccine doses given (0.65%) were reported. 57 ARs (12.3%) were determined to be allergic (10 after the second dose), 356 were nonallergic, and 51 (11.0%) were undetermined. Of the 47 first-dose allergic ARs, 30 (63.8%) received a second dose, 16 did not complete the vaccine series, and 1 had no data. 3 employees received an alternative Cov19V. Of the 356 nonallergic ARs, 110 were following second dose, 2 were following Janssen, and 4 had no data. 228 of first dose reactions (95.0%, 228/240) completed the vaccine series. 22/57 (38.6%) allergic ARs versus 38/356 (10.7%) nonallergic ARs required ER transfer. More allergic ARs were categorized as moderate/severe (80.7%, 46/57) than nonallergic ARs (66.3%, 236/356).
Conclusion(s): Cov19V ARs are extremely uncommon with nonallergic AR more common than allergic. A vast majority of ARs, allergic or nonallergic, are able to receive subsequent Cov19V. Employees with allergic ARs were less likely to receive a second Cov19V and more frequently required emergent medical evaluation compared to those with nonallergic ARs.
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