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Context in diagnosis and management of patients is a vexing phenomenon in medicine and health professions education that can lead to unwanted variation in clinical reasoning performance and even errors that cause patient harm. Studies have examined individual-, team-, and system-level contextual factors, but the ways in which multiple contextual factors can interact, how both distracting and enabling factors can impact performance and error, and the boundaries between context and content information are not well understood. In this paper, we use a theory-based approach to enhance our understanding of context. We introduce a multilevel perspective on context that extends prior models of clinical reasoning and propose a micro-meso-macro framework to provide a more integrated understanding of how clinical reasoning is both influenced by and emerges from multiple contextual factors. The multilevel approach can also be used to study other social phenomena in medicine such as professionalism, learning, burnout, and implicit bias. We call for a new paradigm in clinical reasoning research and education that uses multilevel theory and analysis to enhance clinical reasoning performance expertise and improve the quality of patient care.

Background The COVID-19 pandemic required clinicians to care for a disease with evolving characteristics while also adhering to care changes (e.g., physical distancing practices) that might lead to diagnostic errors (DEs). Objective To determine the frequency of DEs and their causes among patients hospitalized under investigation (PUI) for COVID-19. Design Retrospective cohort. Setting Eight medical centers affiliated with the Hospital Medicine ReEngineering Network (HOMERuN). Target population Adults hospitalized under investigation (PUI) for COVID-19 infection between February and July 2020. Measurements We randomly selected up to 8 cases per site per month for review, with each case reviewed by two clinicians to determine whether a DE (defined as a missed or delayed diagnosis) occurred, and whether any diagnostic process faults took place. We used bivariable statistics to compare patients with and without DE and multivariable models to determine which process faults or patient factors were associated with DEs. Results Two hundred and fifty-seven patient charts underwent review, of which 36 (14%) had a diagnostic error. Patients with and without DE were statistically similar in terms of socioeconomic factors, comorbidities, risk factors for COVID-19, and COVID-19 test turnaround time and eventual positivity. Most common diagnostic process faults contributing to DE were problems with clinical assessment, testing choices, history taking, and physical examination (all p Limitations Results are limited by available documentation and do not capture communication between providers and patients. Conclusion Among PUI patients, DEs were common and not associated with pandemic-related care changes, suggesting the importance of more general diagnostic process gaps in error propagation.

Background The diagnosis of urinary tract infection (UTI) is challenging among hospitalized older adults, particularly among those with altered mental status. Objective To determine the diagnostic accuracy of procalcitonin (PCT) for UTI in hospitalized older adults. Design We performed a prospective cohort study of older adults (≥65 years old) admitted to a single hospital with evidence of pyuria on urinalysis. PCT was tested on initial blood samples. The reference standard was a clinical definition that included the presence of a positive urine culture and any symptom or sign of infection referable to the genitourinary tract. We also surveyed the treating physicians for their clinical judgment and performed expert adjudication of cases for the determination of UTI. Participants Two hundred twenty-nine study participants at a major academic medical center. Main Measures We calculated the area under the receiver operating characteristic curve (AUC) of PCT for the diagnosis of UTI. Key Results In this study cohort, 61 (27%) participants met clinical criteria for UTI. The median age of the overall cohort was 82.6 (IQR 74.9–89.7) years. The AUC of PCT for the diagnosis of UTI was 0.56 (95% CI, 0.46–0.65). A series of sensitivity analyses on UTI definition, which included using a decreased threshold for bacteriuria, the treating physicians’ clinical judgment, and independent infectious disease specialist adjudication, confirmed the negative result. Conclusions Our findings demonstrate that PCT has limited value in the diagnosis of UTI among hospitalized older adults. Clinicians should be cautious using PCT for the diagnosis of UTI in hospitalized older adults. Supplementary Information The online version contains supplementary material available at 10.1007/s11606-021-07265-8.

Most medical students entering clerkships have limited understanding of clinical reasoning concepts. The value of teaching theories of clinical reasoning and cognitive biases to first-year medical students is unknown. This study aimed to evaluate the value of explicitly teaching clinical reasoning theory and cognitive bias to first-year medical students.Using Kolb's experiential learning model, we introduced dual process theory, script theory, and cognitive biases in teaching clinical reasoning to first-year medical students at an academic medical center in New York City between January and June 2020. Due to the COVID-19 pandemic, instruction was transitioned to a distance learning format in March 2020. The curriculum included a series of written clinical reasoning examinations with facilitated small group discussions. Written self-assessments prompted each student to reflect on the experience, draw conclusions about their clinical reasoning, and plan for future encounters involving clinical reasoning. We evaluated the value of the curriculum using mixed-methods to analyze faculty assessments, student self-assessment questionnaires, and an end-of-curriculum anonymous questionnaire eliciting student feedback.Among 318 total examinations of 106 students, 254 (80%) had a complete problem representation, while 199 (63%) of problem representations were considered concise. The most common cognitive biases described by students in their clinical reasoning were anchoring bias, availability bias, and premature closure. Four major themes emerged as valuable outcomes of the CREs as identified by students: (1) synthesis of medical knowledge; (2) enhanced ability to generate differential diagnoses; (3) development of self-efficacy related to clinical reasoning; (4) raised awareness of personal cognitive biases.We found that explicitly teaching clinical reasoning theory and cognitive biases using an experiential learning model provides first-year medical students with valuable opportunities for developing knowledge, skills, and self-efficacy related to clinical reasoning.

Aims Autonomic dysfunction has been associated with risky drinking and alcohol use disorder (AUD). Although autonomic nervous system (ANS) activity has been attributed to the ventromedial prefrontal cortex (VmPFC)-limbic-striatal regions, the specific role of ANS disruption in AUD and its association with these regions remain unclear. Using functional magnetic resonance imaging (fMRI) and concurrent electrocardiogram (ECG), the current study examined neural correlates of ANS activity in AUD and its role in AUD pathology. Methods Demographically matched 20 AUD patients and 20 social drinkers (SD) completed an fMRI task involving repeated exposure to stress, alcohol-cue and neutral-relaxing images in a block design. Based on the known VmPFC-limbic-striatal functions involved in emotions, reward and the ANS, we performed a regions of interest (ROI) analysis to examine the associations between ANS activity and neural responses in the VmPFC, amygdala, and ventral striatum. Results Across conditions, AUD patients showed significantly higher levels of overall heart rate (HR) and approximate entropy (ApEn) compared to SD (Ps Discussion Our findings demonstrate ANS disruption in AUD indexed by high overall HR and ApEn. The association between ApEn and rVmPFC response suggests that ApEn may play a role in modulating drinking via interactions with neural regions of emotion regulation. These findings provide insight into patterns of ANS disruption and their relevance to AUD pathology.

Background Laboratory parameters and the associated clinical outcomes have been an area of focus in COVID-19 research globally. Purpose We performed a scoping review to synthesize laboratory values described in the literature and their associations with mortality and disease severity. Methods We identified all primary studies involving laboratory values with clinical outcomes as a primary endpoint by performing data searches in various systematic review databases until 10th August, 2020. Two reviewers independently reviewed all abstracts (13,568 articles) and full text (1126 articles) data. A total of 529 studies involving 165,020 patients from 28 different countries were included. Investigation of the number of studies and patients from a geographical perspective showed that the majority of published literature from January–March 2020 to April–June 2020 was from Asia, though there was a temporal shift in published studies to Europe and the Americas. For each laboratory value, the proportion of studies that noted a statistically significant (p

Background The clinical course of COVID-19 includes multiple disease phases. Data describing post-hospital discharge outcomes may provide insight into disease course. Studies describing post-hospitalization outcomes of adults following COVID-19 infection are limited to electronic medical record review, which may underestimate the incidence of outcomes. Objective To determine 30-day post-hospitalization outcomes following COVID-19 infection. Design Retrospective cohort study Setting Quaternary referral hospital and community hospital in New York City. Participants COVID-19 infected patients discharged alive from the emergency department (ED) or hospital between March 3 and May 15, 2020. Measurement Outcomes included return to an ED, re-hospitalization, and mortality within 30 days of hospital discharge. Results Thirty-day follow-up data were successfully collected on 94.6% of eligible patients. Among 1344 patients, 16.5% returned to an ED, 9.8% were re-hospitalized, and 2.4% died. Among patients who returned to the ED, 50.0% (108/216) went to a different hospital from the hospital of the index presentation, and 61.1% (132/216) of those who returned were re-hospitalized. In Cox models adjusted for variables selected using the lasso method, age (HR 1.01 per year [95% CI 1.00–1.02]), diabetes (1.54 [1.06–2.23]), and the need for inpatient dialysis (3.78 [2.23–6.43]) during the index presentation were independently associated with a higher re-hospitalization rate. Older age (HR 1.08 [1.05–1.11]) and Asian race (2.89 [1.27–6.61]) were significantly associated with mortality. Conclusions Among patients discharged alive following their index presentation for COVID-19, risk for returning to a hospital within 30 days of discharge was substantial. These patients merit close post-discharge follow-up to optimize outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s11606-021-06924-0.

Trauma and chronic pain frequently co-occur, but the underlying neurological mechanisms are poorly understood. The current study investigated the neural correlates of stress and physical symptoms in trauma patients using functional magnetic resonance imaging (fMRI) and follow-up smartphone surveys. Participants were 10 patients diagnosed with Trauma- and Stressor-Related Disorders and 18 demographically-matched healthy controls who completed a fMRI stress provocation task in which they viewed stressful and neutral-relaxing images. Subsequently, participants completed daily smartphone surveys which prospectively monitored their stress and physical symptoms for 30 days. The trauma group experienced a significantly higher frequency of physical symptoms than controls during the follow-up period. During stress, trauma patients exhibited increased activity in the hippocampus, insula, and sensorimotor areas, but decreased activity in the ventromedial prefrontal cortex (vmPFC), lateral prefrontal cortex (LPFC), and dorsal striatum relative to controls. In all participants, higher physical symptom frequency was significantly associated with a hyperactive left hippocampal response to stress. The current study reports that trauma is characterized by greater physical symptoms and decreased prefrontal but increased limbic responses to stress. Our findings suggest that trauma may increase physical health symptoms by compromising hippocampal function, which could also increase vulnerability to stress- and pain-related disorders.

BACKGROUND: COVID-19 has affected millions of people, and several chronic medical conditions appear to increase the risk of severe COVID-19. However, our understanding of COVID-19 outcomes in patients with CKD remains limited. METHODS: This was a retrospective cohort study of patients with and without CKD consecutively admitted with COVID-19 to three affiliated hospitals in New York City. Pre-COVID-19 CKD diagnoses were identified by billing codes and verified by manual chart review. In-hospital mortality was compared between patients with and without underlying CKD. Logistic regression was used to adjust this analysis for confounders and to identify patient characteristics associated with mortality. RESULTS: We identified 280 patients with CKD, and 4098 patients without CKD hospitalized with COVID-19. The median age of the CKD group was 75 (65–84) years, and age of the non-CKD group 62 (48–75) years. Baseline (pre-COVID-19) serum creatinine in patients with CKD was 1.5 (1.2–2.2) mg/dl. In-hospital mortality was 30% in patients with CKD versus 20% in patients without CKD (P70 years) had higher mortality than their age-matched control patients without CKD. In patients with CKD, factors associated with in-hospital mortality were age (adjusted OR, 1.09 [95% CI, 1.06 to 1.12]), P0.3 mg/dl above the baseline (adjusted OR 2.6 [95% CI, 1.2 to 5.4]P=0.01), and diagnosis of acute on chronic kidney injury during hospitalization (adjusted OR 4.6 [95% CI, 2.3 to 8.9], P

As the Coronavirus disease 2019 (COVID-19) pandemic spread to the US, so too did descriptions of an associated coagulopathy and thrombotic complications. Hospitals created institutional protocols for inpatient management of COVID-19 coagulopathy and thrombosis in response to this developing data. We collected and analyzed protocols from 21 US academic medical centers developed between January and May 2020. We found greatest consensus on recommendations for heparin-based pharmacologic venous thromboembolism (VTE) prophylaxis in COVID-19 patients without contraindications. Protocols differed regarding incorporation of D-dimer tests, dosing of VTE prophylaxis, indications for post-discharge pharmacologic VTE prophylaxis, how to evaluate for VTE, and the use of empiric therapeutic anticoagulation. These findings support ongoing efforts to establish international, evidence-based guidelines., Highlights • COVID-19 protocols agreed on heparin-based venous thromboembolism prophylaxis. • Disagreement on thrombosis risk and diagnosis, D-dimer, empiric anticoagulation • Cumulative incidence of COVID-19 did not correlate with specific recommendations. • Framework for frontline providers and hospitals to evaluate practices and outcomes

Introduction Admissions for acute bacterial skin and skin structure infections (ABSSSI) are often prolonged because of intravenous (IV) antibiotics. Use of a long-acting IV antibiotic may reduce length of stay (LOS) on a hospitalist service. The ENHANCE ABSSSI trial sought to determine the impact on LOS and work productivity in patients treated with a long-acting IV antibiotic, dalbavancin, vs. usual care at an urban tertiary-care center. Methods A single-center, pre- vs. post-period pragmatic trial at Weill-Cornell Medical Center assessed usual care for consecutively enrolled admitted ABSSSI patients during an observational period (pre-period). Identification and treatment of eligible admitted ABSSSI patients with dalbavancin were implemented in the post-period. Those with life-threatening infections, requiring multiple antibiotics/intensive care, or with unstable comorbidities were excluded. Outcomes were assessed over a 44-day follow-up period. Results Of 48 and 43 patients enrolled, respectively, in the pre- and post-periods, mean infection-related LOS was reduced in the post-period (3.2 days vs. 4.8 days; P = 0.003). Similar results were found in an adjusted LOS analysis. Work productivity and activity impairment outcomes significantly improved in the post-period (P ≤ 0.01). Complete response rates were similar: 50% (pre-period) and 57% (post-period). Among AEs identified, 17% (n = 7) were found to have possible causal relation to dalbavancin in the post-period. Few AEs were serious (n = 3; 7% post-period versus n = 1; 2% pre-period). Conclusion After implementing the ENHANCE ABSSSI pathway, LOS was significantly reduced by almost 2 days, with potential improvements in work productivity and ability to complete daily activities. Trial Registration ClinicalTrials.gov identifier, NCT03233438. Funding Allergan plc. Electronic supplementary material The online version of this article (10.1007/s40121-019-00275-4) contains supplementary material, which is available to authorized users.

There is emerging interest in understanding group decision making among a team of health professionals. Groupthink, a term coined by Irving Janis to depict premature consensus seeking in highly cohesive groups, is a theory that has been widely discussed in disciplines outside health care. However, it remains unclear how it has been conceptualized, studied, and mitigated in the context of health professionals conducting patient care. This scoping review aimed to examine the conceptualization of groupthink in health care, empirical research conducted in healthcare teams, and recommendations to avoid groupthink. Eight databases were systematically searched for articles focusing on groupthink among health professional teams using a scoping review methodology. A total of 22 articles were included—most were commentaries or narrative reviews with only four empirical research studies. This review found that focus on groupthink and group decision making in medicine is relatively new and growing in interest. Few empirical studies on groupthink in health professional teams have been performed and there is conceptual disagreement on how to interpret groupthink in the context of clinical practice. Future research should develop a theoretical framework that applies groupthink theory to clinical decision making and medical education, validate the groupthink framework in clinical settings, develop measures of groupthink, evaluate interventions that mitigate groupthink in clinical practice, and examine how groupthink may be situated amidst other emerging social cognitive theories of collaborative clinical decision making.

Background Multiplex polymerase chain reaction (PCR) panels allow for rapid detection or exclusion of pathogens causing meningitis and encephalitis (ME). The clinical impact of rapid multiplex PCR ME panel results on the duration of empiric antibiotic therapy is not well characterized. Methods We performed a retrospective prepost study at our institution that evaluated the clinical impact of a multiplex PCR ME panel among adults with suspected bacterial meningitis who received empiric antibiotic therapy and underwent lumbar puncture in the emergency department. The primary outcome was the duration of empiric antibiotic therapy. Results The positive pathogen detection rates were similar between pre- and post-multiplex PCR ME panel periods (17.5%, 24 of 137 vs 20.3%, 14 of 69, respectively). The median duration of empiric antibiotic therapy was significantly reduced in the post-multiplex PCR ME panel period compared with the pre-multiplex PCR ME panel period (34.7 vs 12.3 hours, P = .01). At any point in time, 46% more patients in the post-multiplex PCR ME panel period had empiric antibiotic therapy discontinued or de-escalated compared with the pre-multiplex PCR ME panel period (sex- and immunosuppressant use-adjusted hazard ratio 1.46, P = .01). The median hospital length of stay was shorter in the post-multiplex PCR ME panel period (3 vs 4 days, P = .03). Conclusions The implementation of the multiplex PCR ME panel for bacterial meningitis reduced the duration of empiric antibiotic therapy and possibly hospital length of stay compared with traditional microbiological testing methods., In this pre-post study, implementation of a multiplex polymerase chain reaction panel testing for agents of meningitis significantly reduced the duration of empiric antibiotic therapy, time to targeted therapy, and hospital length of stay compared with traditional microbiological testing methods.

The novel coronavirus disease-19 (COVID-19) pandemic caused by SARS-CoV-2 has ravaged global healthcare with previously unseen levels of morbidity and mortality. To date, methods to predict the clinical course, which ranges from the asymptomatic carrier to the critically ill patient in devastating multi-system organ failure, have yet to be identified. In this study, we performed large-scale integrative multi-omics analyses of serum obtained from COVID-19 patients with the goal of uncovering novel pathogenic complexities of this disease and identifying molecular signatures that predict clinical outcomes. We assembled a novel network of protein-metabolite interactions in COVID-19 patients through targeted metabolomic and proteomic profiling of serum samples in 330 COVID-19 patients compared to 97 non-COVID, hospitalized controls. Our network identified distinct protein-metabolite cross talk related to immune modulation, energy and nucleotide metabolism, vascular homeostasis, and collagen catabolism. Additionally, our data linked multiple proteins and metabolites to clinical indices associated with long-term mortality and morbidity, such as acute kidney injury. Finally, we developed a novel composite outcome measure for COVID-19 disease severity and created a clinical prediction model using a set of 33 metabolites. The model significantly improved the identification of key events of critical illness such as prolonged hospitalization, supplemental oxygen requirement, acute kidney injury (AKI), and acute respiratory distress syndrome (ARDS), beyond those achieved using the more traditional risk factors of age, gender, and BMI.

Covid-19 in New York City In this series of 393 consecutive patients admitted with Covid-19 to two New York City hospitals from March 3 to March 27, a third of patients received invasive mechanical...

OBJECTIVE: The aim of the study was to determine the main factors contributing to hospital readmissions and their potential preventability after a coronavirus disease 2019 (COVID-19) hospitalization at 2 New York City hospitals. METHODS: This was a retrospective study at 2 affiliated New York City hospitals located in the Upper East Side and Lower Manhattan neighborhoods. We performed case reviews using the Hospital Medicine Reengineering Network framework to determine potentially preventable readmissions among patients hospitalized for COVID-19 between March 3, 2020 (date of first case) and April 27, 2020, and readmitted to either of the 2 hospitals within 30 days of discharge. RESULTS: Among 53 readmissions after hospitalization for COVID-19, 44 (83%) were deemed not preventable and 9 (17%) were potentially preventable. Nonpreventable readmissions were mostly due to disease progression or complications of COVID-19 (37/44, 84%). Main factors contributing to potentially preventable readmissions were issues with initial disposition (5/9, 56%), premature discharge (3/9, 33%), and inappropriate readmission (1/9, 11%) for someone who likely did not require rehospitalization. CONCLUSIONS: Most readmissions after a COVID-19 hospitalization were not preventable and a consequence of the natural progression of the disease, specifically worsening dyspnea or hypoxemia. Some readmissions were potentially preventable, mostly because of issues with disposition that were directly related to challenges posed by the ongoing COVID-19 pandemic. Clinicians should be aware of challenges with disposition related to circumstances of the COVID-19 pandemic.

Increasing evidence has shown that Coronavirus disease 19 (COVID-19) severity is driven by a dysregulated immunologic response. We aimed to assess the differences in inflammatory cytokines in COVID-19 patients compared to contemporaneously hospitalized controls and then analyze the relationship between these cytokines and the development of Acute Respiratory Distress Syndrome (ARDS), Acute Kidney Injury (AKI) and mortality. In this cohort study of hospitalized patients, done between March third, 2020 and April first, 2020 at a quaternary referral center in New York City we included adult hospitalized patients with COVID-19 and negative controls. Serum specimens were obtained on the first, second, and third hospital day and cytokines were measured by Luminex. Autopsies of nine cohort patients were examined. We identified 90 COVID-19 patients and 51 controls. Analysis of 48 inflammatory cytokines revealed upregulation of macrophage induced chemokines, T-cell related interleukines and stromal cell producing cytokines in COVID-19 patients compared to the controls. Moreover, distinctive cytokine signatures predicted the development of ARDS, AKI and mortality in COVID-19 patients. Specifically, macrophage-associated cytokines predicted ARDS , T cell immunity related cytokines predicted AKI and mortality was was associated with cytokines of activated immune pathways, of which IL-13 was universally correlated with ARDS, AKI and mortality. Histopathological examination of the autopsies showed diffuse alveolar damage with significant mononuclear inflammatory cell infiltration. Additionally, the kidneys demonstrated glomerular sclerosis, tubulointerstitial lymphocyte infiltration and cortical and medullary atrophy. These patterns of cytokine expression offer insight into the pathogenesis of COVID-19 disease, its severity, and subsequent lung and kidney injury suggesting more targeted treatment strategies.

Introduction: COVID-19 is a respiratory syndrome with high rates of mortality, and findings from the ECG on hospital presentation have been shown to increase the odds of death. We thus hypothesized that findings from the presenting ECG could discriminate the risk of death in high risk subgroups, and sought to create an ECG risk score for death in COVID-19. Methods: We performed a retrospective cohort study in patients with COVID-19 who had an ECG at or near hospital admission. Clinical characteristics were manually abstracted from the electronic health record; ECG data were digitally extracted from the first ECG in each patient, and Bazett-corrected QT interval and ST segment deviation at the M-point (STm, in μV) were quantified in all 12 leads. Our primary outcome was death. Results: 710 patients who presented to a large teaching hospital with COVID-19 underwent an ECG. The mean age was 63 ± 16 years, 37% were women, 62% of patients were non-white, and 56% had hypertension; 78 (11%) died. In a multivariable logistic regression that included age, ECG, and clinical characteristics, the presence of one or more atrial premature contractions (OR=3.56, 95% CI 1.80-7.02, p80, Figure ). Conclusions: A simple ECG risk score (including APCs, RBBB/IVB, STmV5V6 ≤ -50 μV, STmV2

BackgroundThe spread of SARS-CoV-2 and the COVID-19 pandemic have caused significant morbidity and mortality worldwide. The clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 and HIV co-infection remain uncertain.MethodsWe conducted a matched retrospective cohort study of adults hospitalized with a COVID-19 illness in New York City between March 3, 2020, and May 15, 2020. We matched 30 people with HIV (PWH) with 90 control group patients without HIV based on age, sex, and race/ethnicity. Using electronic health record data, we compared demographic characteristics, clinical characteristics, and clinical outcomes between PWH and control patients.ResultsIn our study, the median age (interquartile range) was 60.5 (56.6–70.0) years, 20% were female, 30% were black, 27% were white, and 24% were of Hispanic/Latino/ethnicity. There were no significant differences between PWH and control patients in presenting symptoms, duration of symptoms before hospitalization, laboratory markers, or radiographic findings on chest x-ray. More patients without HIV required a higher level of supplemental oxygen on presentation than PWH. There were no differences in the need for invasive mechanical ventilation during hospitalization, length of stay, or in-hospital mortality.ConclusionsThe clinical manifestations and outcomes of COVID-19 among patients with SARS-CoV-2 and HIV co-infection were not significantly different than patients without HIV co-infection. However, PWH were hospitalized with less severe hypoxemia, a finding that warrants further investigation.

A surge of patients with coronavirus disease 2019 (COVID-19) presenting to New York City hospitals in March 2020 led to a sharp increase in blood culture utilization, which overwhelmed the capacity of automated blood culture instruments. We sought to evaluate the utilization and diagnostic yield of blood cultures during the COVID-19 pandemic to determine prevalence and common etiologies of bacteremia and to inform a diagnostic approach to relieve blood culture overutilization. We performed a retrospective cohort analysis of 88,201 blood cultures from 28,011 patients at a multicenter network of hospitals within New York City to evaluate order volume, positivity rate, time to positivity, and etiologies of positive cultures in COVID-19., A surge of patients with coronavirus disease 2019 (COVID-19) presenting to New York City hospitals in March 2020 led to a sharp increase in blood culture utilization, which overwhelmed the capacity of automated blood culture instruments. We sought to evaluate the utilization and diagnostic yield of blood cultures during the COVID-19 pandemic to determine prevalence and common etiologies of bacteremia and to inform a diagnostic approach to relieve blood culture overutilization. We performed a retrospective cohort analysis of 88,201 blood cultures from 28,011 patients at a multicenter network of hospitals within New York City to evaluate order volume, positivity rate, time to positivity, and etiologies of positive cultures in COVID-19. Ordering volume increased by 34.8% in the second half of March 2020 compared to the level in the first half of the month. The rate of bacteremia was significantly lower among COVID-19 patients (3.8%) than among COVID-19-negative patients (8.0%) and those not tested (7.1%) (P

Highlights • Findings of left and right sided heart disease on the presentation electrocardiogram are associated with death in COVID-19 • Right bundle branch block in COVID-19 is likely secondary to acute right ventricular distension, and could represent the at-risk right ventricle. • Markers of left ventricular stiffness (atrial premature contractions, prolonged intraventricular conduction, and ischemic repolarization abnormalities) are associated with death., Background Coronavirus disease 2019 (COVID-19) is a respiratory syndrome with high rates of mortality, and there is a need for easily obtainable markers to provide prognostic information. We sought to determine whether the electrocardiogram (ECG) on hospital presentation provides prognostic information, specifically related to death. Methods and Results We performed a retrospective cohort study in patients with COVID-19 who had an ECG at or near hospital admission. Clinical characteristics and ECG variables were manually abstracted from the electronic health record and first ECG. Our primary outcome was death. There were 756 patients who presented to a large New York City teaching hospital with COVID-19 who underwent an ECG. The mean age was 63.3 ± 16 years, 37% were women, 61% of patients were nonwhite, and 57% had hypertension; 90 (11.9%) died. In a multivariable logistic regression that included age, ECG, and clinical characteristics, the presence of one or more atrial premature contractions (odds ratio [OR] 2.57, 95% confidence interval [CI] 1.23–5.36, P = .01), a right bundle branch block or intraventricular block (OR 2.61, 95% CI 1.32–5.18, P = .002), ischemic T-wave inversion (OR 3.49, 95% CI 1.56–7.80, P = .002), and nonspecific repolarization (OR 2.31, 95% CI 1.27–4.21, P = .006) increased the odds of death. ST elevation was rare (n = 5 [0.7%]). Conclusions We found that patients with ECG findings of both left-sided heart disease (atrial premature contractions, intraventricular block, repolarization abnormalities) and right-sided disease (right bundle branch block) have higher odds of death. ST elevation at presentation was rare., Graphical Abstract Image, graphical abstract

Objective To characterize patients with coronavirus disease 2019 (covid-19) in a large New York City medical center and describe their clinical course across the emergency department, hospital wards, and intensive care units. Design Retrospective manual medical record review. Setting NewYork-Presbyterian/Columbia University Irving Medical Center, a quaternary care academic medical center in New York City. Participants The first 1000 consecutive patients with a positive result on the reverse transcriptase polymerase chain reaction assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented to the emergency department or were admitted to hospital between 1 March and 5 April 2020. Patient data were manually abstracted from electronic medical records. Main outcome measures Characterization of patients, including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. Results Of the first 1000 patients, 150 presented to the emergency department, 614 were admitted to hospital (not intensive care units), and 236 were admitted or transferred to intensive care units. The most common presenting symptoms were cough (732/1000), fever (728/1000), and dyspnea (631/1000). Patients in hospital, particularly those treated in intensive care units, often had baseline comorbidities including hypertension, diabetes, and obesity. Patients admitted to intensive care units were older, predominantly male (158/236, 66.9%), and had long lengths of stay (median 23 days, interquartile range 12-32 days); 78.0% (184/236) developed acute kidney injury and 35.2% (83/236) needed dialysis. Only 4.4% (6/136) of patients who required mechanical ventilation were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at three to four days, and at nine days. As of 30 April, 90 patients remained in hospital and 211 had died in hospital. Conclusions Patients admitted to hospital with covid-19 at this medical center faced major morbidity and mortality, with high rates of acute kidney injury and inpatient dialysis, prolonged intubations, and a bimodal distribution of time to intubation from symptom onset.

A surge of patients with coronavirus disease 2019 (COVID-19) presenting to New York City hospitals in March 2020 led to a sharp increase in the utilization of blood cultures, which overwhelmed the capacity of automated blood culture instruments. We sought to evaluate the utilization and diagnostic yield of blood cultures during the COVID-19 pandemic to determine prevalence and common etiologies of bacteremia, and to inform a diagnostic approach to relieve blood culture overutilization. We performed a retrospective cohort analysis of 88,201 blood cultures from 28,011 patients at a multicenter network of hospitals within New York City to evaluate order volume, positivity rate, time to positivity, and etiologies of positive cultures in COVID-19. Ordering volume increased by 34.8% in the second half of March 2020 compared to the first half of the month. The rate of bacteremia was significantly lower among COVID-19 patients (3.8%) than COVID-19 negative patients (8.0%) and those not tested (7.1%), p < 0.001. COVID-19 patients had a high proportion of organisms reflective of commensal skin microbiota, reducing the bacteremia rate to 1.6% when excluded. More than 98% of all positive cultures were detected within 4 days of incubation. Bloodstream infections are very rare for COVID-19 patients, which supports the judicious use of blood cultures in the absence of compelling evidence for bacterial coinfection. Clear communication with ordering providers is necessary to prevent overutilization of blood cultures during COVID-19 surges, and laboratories should consider shortening the incubation period from 5 days to 4 days to free additional capacity.

ObjectiveTo characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient wards, and intensive care units (ICUs).DesignRetrospective manual medical record review.SettingNewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC.ParticipantsThe first 1000 consecutive patients with laboratory-confirmed COVID-19.MethodsWe identified the first 1000 consecutive patients with a positive RT-SARS-CoV-2 PCR test who first presented to the ED or were hospitalized at NYP/CUIMC between March 1 and April 5, 2020. Patient data was manually abstracted from the electronic medical record.Main outcome measuresWe describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition.ResultsAmong the first 1000 patients, 150 were ED patients, 614 were admitted without requiring ICU-level care, and 236 were admitted or transferred to the ICU. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (63.1%). Hospitalized patients, and ICU patients in particular, most commonly had baseline comorbidities including of hypertension, diabetes, and obesity. ICU patients were older, predominantly male (66.9%), and long lengths of stay (median 23 days; IQR 12 to 32 days); 78.0% developed AKI and 35.2% required dialysis. Notably, for patients who required mechanical ventilation, only 4.4% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. As of April 30, 90 patients remained hospitalized and 211 had died in the hospital.ConclusionsHospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset.

Introduction Data extraction from electronic health record (EHR) systems occurs through manual abstraction, automated extraction, or a combination of both. While each method has its strengths and weaknesses, both are necessary for retrospective observational research as well as sudden clinical events, like the COVID-19 pandemic. Assessing the strengths, weaknesses, and potentials of these methods is important to continue to understand optimal approaches to extracting clinical data. We set out to assess automated and manual techniques for collecting medication use data in patients with COVID-19 to inform future observational studies that extract data from the electronic health record (EHR). Materials and Methods For 4,123 COVID-positive patients hospitalized and/or seen in the emergency department at an academic medical center between 03/03/2020 and 05/15/2020, we compared medication use data of 25 medications or drug classes collected through manual abstraction and automated extraction from the EHR. Quantitatively, we assessed concordance using Cohen’s kappa to measure interrater reliability, and qualitatively, we audited observed discrepancies to determine causes of inconsistencies. Results Of the 16 inpatient medications, 11 (69%) demonstrated moderate or better agreement; 7 of those demonstrated strong or almost perfect agreement. Of 9 outpatient medications, 3 (33%) demonstrated moderate agreement, but none achieved strong or almost perfect agreement. We audited 12% of all discrepancies (716/5,790) and, in those audited, observed three principal categories of error: human error in manual abstraction (26%), errors in the extract-transform-load (ETL) or mapping of the automated extraction (41%), and abstraction-query mismatch (33%). Conclusion Our findings suggest many inpatient medications can be collected reliably through automated extraction, especially when abstraction instructions are designed with data architecture in mind. We discuss quality issues, concerns, and improvements for institutions to consider when crafting an approach. During crises, institutions must decide how to allocate limited resources. We show that automated extraction of medications is feasible and make recommendations for how to improve for future iterations.

The emergence of multidrug-resistant bacterial pathogens has led to a global public health emergency and novel therapeutic options and drug-delivery systems are urgently needed. Cefiderocol is a siderophore cephalosporin antibiotic that has recently been developed to combat a variety of bacterial pathogens, including β-lactam- and carbapenem-resistant organisms.This paper provides an overview of the mutational and plasmid-mediated mechanisms of β-lactam and carbapenem resistance, the biochemical pathways of siderophores in bacterial iron metabolism, and how cefiderocol may be able to provide better targeted antimicrobial therapy that escape these drug-resistant mechanisms. We also explore the pharmacokinetics of this new compound as well as results from preclinical and clinical studies.There is an urgent need for novel antimicrobial agents to address the emergence of multidrug-resistant pathogens, which are an increasing cause of morbidity and mortality worldwide. Our understanding of multidrug-resistance and bacterial biochemical pathways continues to expand, and the development of cefiderocol specifically targeting siderophore-mediated iron transport shows potential in escaping mechanisms of drug resistance. Cefiderocol, which demonstrates a favorable side effect profile, has the potential to become first-line therapy for our most aggressive and lethal multidrug-resistant Gram-negative pathogens.

Acute dyspnea is a common chief complaint among patients who visit an emergency room and presents diagnostic challenges for clinicians in both identifying the etiology and determining the clinical severity. The study of biomarkers in the prognostication and risk stratification of these patients has been increasing, including the investigation of the prognostic value for mid-regional pro-adrenomedullin (MR-proADM). Areas covered: In this review, the authors cover what is known about MR-proADM testing in patients presenting with acute dyspnea and the supporting evidence of its prognostic value in common conditions in medical patients with acute dyspnea, including acute heart failure, community acquired pneumonia, acute exacerbation of chronic obstructive pulmonary disease, and acute pulmonary embolism. Expert commentary: Numerous studies have proposed MR-proADM as a more accurate, prognostic tool in the evaluation of acute dyspnea than other biomarkers and consensus risk scores such as Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA). The authors review recent prospective studies, systematic reviews, and meta-analyses that demonstrate its prognostic value and role in risk stratification, including its use in biomarker-based triage algorithms as part of the diagnostic evaluation of the acutely dyspneic patient.

Background Physicians are constantly asked to evaluate inpatients for possible antibiotic treatment. As part of antibiotic stewardship it is imperative to understand the decision-making process behind a physician’s choice to prescribe antibiotics appropriately in an inpatient setting. Fuzzy Trace Theory (FTT) suggests that physicians use one of two methods in medical decision making; verbatim, employing a comprehensive risk benefit analysis, and gist, considering a bottom line analysis. Methods Seventy-six hospitalists at Weill Cornell Medicine in Manhattan, New York received a survey with two reminders to evaluate their decision-making process. Five basic demographic questions regarding participant gender, race, background, age, and years in practice were asked. A clinical vignette describing an inpatient with a possible urinary tract infection (UTI) was followed with statements framing hypothetical antibiotic prescription. A seven point Likert scale with response choices from Strongly Disagree scored as one to Strongly Agree scored as seven was used to assess degree of participant agreement with each statement. Questions were presented in a random order to eliminate possible effects of questions clusters or question order. Results Twenty-six hospitalists completed the survey. Consistent with previous literature, the hospitalists surveyed displayed a gist interpretation of the risks and benefits of antibiotics, with a mean Likert scale score of 5.54 agreeing that there are benefits to antibiotic prescription, and a mean Likert scale score of 6.04, agreeing that there are risks to antibiotic prescription. . However, the clinicians surveyed ultimately found antibiotics to be a necessary risk given the possible benefit of improving patient health. The hospitalists surveyed also did not view antibiotic prescription to be a product of pressure from patient families, agreeing by a mean Likert scale score of 5.08 that the patient’s family will trust their physician to prescribe antibiotics if needed. Conclusion These findings suggest that physician education to reduce overprescribing of antibiotics should underscore possible antibiotic risk, despite potential benefit. Disclosures Marshall J. Glesby, MD, Enzychem (Consultant)Gilead (Grant/Research Support)ReAlta Life Sciences (Consultant)Regeneron (Consultant, Grant/Research Support)Sobi (Consultant)Springer (Other Financial or Material Support, Royalties)UpToDate (Other Financial or Material Support, Royalties) Justin J. Choi, MD, Allergan (Consultant, Grant/Research Support)Roche (Consultant, Grant/Research Support)

Procalcitonin has emerged as a reliable marker of acute bacterial infection in hospitalized patients and the assay has recently been incorporated into several clinical algorithms to reduce antimicrobial overuse, but its use in patients with end-organ dysfunction is controversial. Areas covered: In this review, the authors examine what is known about procalcitonin testing in patients with organ dysfunction, including those with end-stage renal disease, congestive heart failure, chronic obstructive pulmonary disease, and cirrhosis, and explore how the assay is now being used in the management of non-infectious diseases. Expert commentary: Procalcitonin holds tremendous promise to identify a diverse set of medical conditions beyond those associated with acute bacterial infection, including post-surgical anastomotic leaks, acute kidney injury, and complications after intracerebral hemorrhage. The authors review recent studies examining procalcitonin in these areas and explore how the assay might be used to guide diagnosis and prognosis of non-infectious diseases in the near future.

IMPACT: This work seeks to improve the diagnostic accuracy of urinary tract infection among hospitalized older adults and mitigate antibiotic overuse in this population. OBJECTIVES/GOALS: Primary objective: To determine the diagnostic accuracy of serum procalcitonin (PCT) for the diagnosis of symptomatic urinary tract infection (UTI) in hospitalized older adults. Secondary objectives: (1) To develop a predictive model for the diagnosis of UTI; (2) To determine the ability of PCT in discriminating between lower and upper UTI. METHODS/STUDY POPULATION: We performed a prospective observational cohort study of 228 participants from a single institution. The study population included older adults (age 65 or older) who were hospitalized on the general medicine wards with a possible or suspected urinary tract infection (UTI). Upon obtaining informed consent, serum procalcitonin (PCT) was processed on remnant blood samples collected from the emergency department. We performed additional data collection through the electronic health record to obtain demographic information, clinical characteristics, and other laboratory and imaging results. Clinicians were surveyed for the diagnosis of UTI and charts were adjudicated by independent reviews of the medical record by infectious diseases experts to determine the primary endpoint of symptomatic UTI. RESULTS/ANTICIPATED RESULTS: We anticipate that serum procalcitonin predicts the presence of symptomatic urinary tract infection (UTI) by demonstrating an area under the receiver operating characteristic curve of at least 0.85. A predictive model developed in our cohort for the diagnosis of symptomatic UTI will be improved by the addition of serum PCT to the prediction model. Finally, we anticipate the serum PCT will accurately discriminate between upper and lower UTI. DISCUSSION/SIGNIFICANCE OF FINDINGS: Diagnosis of symptomatic UTI in hospitalized older adults is challenging and may lead to overuse of antibiotics and the development of antibiotic resistance in this vulnerable patient population. Serum procalcitonin offers a novel diagnostic strategy in the diagnosis of symptomatic UTI to enable more appropriate antibiotic therapy.

Graphical abstract, From early March through mid-May 2020, the COVID-19 pandemic overwhelmed hospitals in New York City. In anticipation of ventilator shortages and limited ICU bed capacity, hospital operations prioritized the development of prognostic tools to predict clinical deterioration. However, early experience from frontline physicians observed that some patients developed unanticipated deterioration after having relatively stable periods, attesting to the uncertainty of clinical trajectories among hospitalized patients with COVID-19. Prediction tools that incorporate clinical variables at one time-point, usually on hospital presentation, are suboptimal for patients with dynamic changes and evolving clinical trajectories. Therefore, our study team developed a machine-learning algorithm to predict clinical deterioration among hospitalized COVID-19 patients by extracting clinically meaningful features from complex longitudinal laboratory and vital sign values during the early period of hospitalization with an emphasis on informative missing-ness. To incorporate the evolution of the disease and clinical practice over the course of the pandemic, we utilized a time-dependent cross-validation strategy for model development. Finally, we validated our prediction model on an external validation cohort of COVID-19 patients served in a demographically distinct population from the training cohort. The main finding of our study is the identification of risk profiles of early, late and no clinical deterioration during the course of hospitalization. While risk prediction models that include simple predictors at ED presentation and clinical judgement are able to identify any deterioration vs. no deterioration, our methodology is able to isolate a particular risk group that remain stable initially but deteriorate at a later stage of the course of hospitalization. We demonstrate the superior predictive performance with the utilization of laboratory and vital sign data during the early period of hospitalization compared to the utilization of data at presentation alone. Our results will allow efficient hospital resource allocation and will motivate research in understanding the late deterioration risk group.

OBJECTIVES This study aims to better understand and describe antibiotic prescribing practices and adherence to a procalcitonin (PCT)-guided algorithm in patients undergoing serum PCT testing in adult hospitalized patients. METHODS We performed an observational, retrospective study of 201 randomly selected patients who are aged ≥18 years, admitted to the general medicine floors or step-down unit between 1 January 2017 and 31 December 2017, and had serum PCT testing. Physician adherence to a PCT-guided algorithm was assessed through chart review. RESULTS We found an overall adherence of 64.7%. Adherence was highest for PCT values above 0.25 ng/mL (82.8% for 0.25-0.50 ng/mL and 83.6% for >0.50 ng/mL). Adherence was lower for PCT values less than 0.25 ng/mL (59% for

There remains significant controversy behind the Surviving Sepsis Campaign Guidelines, as evidenced by the Infectious Diseases Society of America refusing to endorse the latest iteration put forth by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. An important stakeholder in this debate has not yet been adequately represented: hospitalists. Areas covered: In this perspective piece, we review the key points in this controversy; specifically, the current guidelines for the identification and management of sepsis. Expert commentary: We believe it is time for hospitalists to weigh in on this important issue by formally commenting on the new guidelines, establishing research priorities, and leading future research studies in the field to help achieve consensus among all clinicians in the appropriate management of sepsis.

Introduction This study aimed to characterize the tumor-infiltrating immune cells population in Kras/tumor protein 53 (Trp53)-driven lung tumors and to evaluate the combinatorial antitumor effect with MEK inhibitor (MEKi), trametinib, and immunomodulatory monoclonal antibodies (mAbs) targeting either programmed death -1 (PD-1) or programmed cell death ligand 1 (PD-L1) in vivo. Methods Trp53FloxFlox;KrasG12D/+;Rosa26LSL-Luciferase/LSL-Luciferase (PKL) genetically engineered mice were used to develop autochthonous lung tumors with intratracheal delivery of adenoviral Cre recombinase. Using these tumor-bearing lungs, tumor-infiltrating immune cells were characterized by both mass cytometry and flow cytometry. PKL-mediated immunocompetent syngeneic and transgenic lung cancer mouse models were treated with MEKi alone as well as in combination with either anti–PD-1 or anti–PD-L1 mAbs. Tumor growth and survival outcome were assessed. Finally, immune cell populations within spleens and tumors were evaluated by flow cytometry and immunohistochemistry. Results Myeloid-derived suppressor cells (MDSCs) were significantly augmented in PKL-driven lung tumors compared to normal lungs of tumor-free mice. PD-L1 expression appeared to be highly positive in both lung tumor cells and, particularly MDSCs. The combinatory administration of MEKi with either anti–PD-1 or anti–PD-L1 mAbs synergistically increased antitumor response and survival outcome compared with single-agent therapy in both the PKL-mediated syngeneic and transgenic lung cancer models. Theses combinational treatments resulted in significant increases of tumor-infiltrating CD8+ and CD4+ T cells, whereas attenuation of CD11b+/Gr-1high MDSCs, in particular, Ly6Ghigh polymorphonuclear-MDSCs in the syngeneic model. Conclusions These findings suggest a potential therapeutic approach for untargetable Kras/p53-driven lung cancers with synergy between targeted therapy using MEKi and immunotherapies.

Antimicrobial peptides (AMPs) constitute an important part of innate host defense. Possibly limiting the therapeutic potential of AMPs is the fact that bacteria have developed AMP resistance mechanisms during their co-evolution with humans. However, there is no direct evidence that AMP resistance per se is important during an infection. Here we show that the Staphylococcus aureus Pmt ABC transporter defends the bacteria from killing by important human AMPs and elimination by human neutrophils. By showing that Pmt contributes to virulence during skin infection in an AMP-dependent manner, we provide evidence that AMP resistance plays a key role in bacterial infection.