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Background: Accurate medical coding is essential for clinical and administrative purposes but complicated, time-consuming, and biased. This study compares Retrieval-Augmented Generation (RAG)-enhanced LLMs to provider-assigned codes in producing ICD-10-CM codes from emergency department (ED) clinical records., Methods: Retrospective cohort study using 500 ED visits randomly selected from the Mount Sinai Health System between January and April 2024. The RAG system integrated past 1,038,066 ED visits data (2021-2023) into the LLMs' predictions to improve coding accuracy. Nine commercial and open-source LLMs were evaluated. The primary outcome was a head-to-head comparison of the ICD-10-CM codes generated by the RAG-enhanced LLMs and those assigned by the original providers. A panel of four physicians and two LLMs blindly reviewed the codes, comparing the RAG-enhanced LLM and provider-assigned codes on accuracy and specificity., Findings: RAG-enhanced LLMs demonstrated superior performance to provider coders in both the accuracy and specificity of code assignments. In a targeted evaluation of 200 cases where discrepancies existed between GPT-4 and provider-assigned codes, human reviewers favored GPT-4 for accuracy in 447 instances, compared to 277 instances where providers' codes were preferred (p<0.001). Similarly, GPT-4 was selected for its superior specificity in 509 cases, whereas human coders were preferred in only 181 cases (p<0.001). Smaller open-access models, such as Llama-3.1-70B, also demonstrated substantial scalability when enhanced with RAG, with 218 instances of accuracy preference compared to 90 for providers' codes. Furthermore, across all models, the exact match rate between LLM-generated and provider-assigned codes significantly improved following RAG integration, with Qwen-2-7B increasing from 0.8% to 17.6% and Gemma-2-9b-it improving from 7.2% to 26.4%., Interpretation: RAG-enhanced LLMs improve medical coding accuracy in EDs, suggesting clinical workflow applications. These findings show that generative AI can improve clinical outcomes and reduce administrative burdens., Funding: This work was supported in part through the computational and data resources and staff expertise provided by Scientific Computing and Data at the Icahn School of Medicine at Mount Sinai and supported by the Clinical and Translational Science Awards (CTSA) grant UL1TR004419 from the National Center for Advancing Translational Sciences. Research reported in this publication was also supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD026880 and S10OD030463. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript., Twitter Summary: A study showed AI models with retrieval-augmented generation outperformed human doctors in ED diagnostic coding accuracy and specificity. Even smaller AI models perform favorably when using RAG. This suggests potential for reducing administrative burden in healthcare, improving coding efficiency, and enhancing clinical documentation.

Objectives: Machine learning algorithms can outperform older methods in predicting clinical deterioration, but rigorous prospective data on their real-world efficacy are limited. We hypothesized that real-time machine learning generated alerts sent directly to front-line providers would reduce escalations., Design: Single-center prospective pragmatic nonrandomized clustered clinical trial., Setting: Academic tertiary care medical center., Patients: Adult patients admitted to four medical-surgical units. Assignment to intervention or control arms was determined by initial unit admission., Interventions: Real-time alerts stratified according to predicted likelihood of deterioration sent either to the primary team or directly to the rapid response team (RRT). Clinical care and interventions were at the providers' discretion. For the control units, alerts were generated but not sent, and standard RRT activation criteria were used., Measurements and Main Results: The primary outcome was the rate of escalation per 1000 patient bed days. Secondary outcomes included the frequency of orders for fluids, medications, and diagnostic tests, and combined in-hospital and 30-day mortality. Propensity score modeling with stabilized inverse probability of treatment weight (IPTW) was used to account for differences between groups. Data from 2740 patients enrolled between July 2019 and March 2020 were analyzed (1488 intervention, 1252 control). Average age was 66.3 years and 1428 participants (52%) were female. The rate of escalation was 12.3 vs. 11.3 per 1000 patient bed days (difference, 1.0; 95% CI, -2.8 to 4.7) and IPTW adjusted incidence rate ratio 1.43 (95% CI, 1.16-1.78; p < 0.001). Patients in the intervention group were more likely to receive cardiovascular medication orders (16.1% vs. 11.3%; 4.7%; 95% CI, 2.1-7.4%) and IPTW adjusted relative risk (RR) (1.74; 95% CI, 1.39-2.18; p < 0.001). Combined in-hospital and 30-day-mortality was lower in the intervention group (7% vs. 9.3%; -2.4%; 95% CI, -4.5% to -0.2%) and IPTW adjusted RR (0.76; 95% CI, 0.58-0.99; p = 0.045)., Conclusions: Real-time machine learning alerts do not reduce the rate of escalation but may reduce mortality., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

The decision to extubate patients on invasive mechanical ventilation is critical; however, clinician performance in identifying patients to liberate from the ventilator is poor. Machine Learning-based predictors using tabular data have been developed; however, these fail to capture the wide spectrum of data available. Here, we develop and validate a deep learning-based model using routinely collected chest X-rays to predict the outcome of attempted extubation. We included 2288 serial patients admitted to the Medical ICU at an urban academic medical center, who underwent invasive mechanical ventilation, with at least one intubated CXR, and a documented extubation attempt. The last CXR before extubation for each patient was taken and split 79/21 for training/testing sets, then transfer learning with k-fold cross-validation was used on a pre-trained ResNet50 deep learning architecture. The top three models were ensembled to form a final classifier. The Grad-CAM technique was used to visualize image regions driving predictions. The model achieved an AUC of 0.66, AUPRC of 0.94, sensitivity of 0.62, and specificity of 0.60. The model performance was improved compared to the Rapid Shallow Breathing Index (AUC 0.61) and the only identified previous study in this domain (AUC 0.55), but significant room for improvement and experimentation remains.

Objectives: Hospitalized patients with severe obesity require adapted hospital management. The aim of this study was to evaluate a machine learning model to predict in-hospital mortality among this population., Methods: Data of unselected consecutive emergency department admissions of hospitalized patients with severe obesity (BMI ≥ 40 kg/m 2 ) was analyzed. Data was retrieved from five hospitals from the Mount Sinai health system, New York. The study time frame was between January 2011 and December 2019. Data was used to train a gradient-boosting machine learning model to identify in-hospital mortality. The model was trained and evaluated based on the data from four hospitals and externally validated on held-out data from the fifth hospital., Results: A total of 14,078 hospital admissions of inpatients with severe obesity were included. The in-hospital mortality rate was 297/14,078 (2.1%). In univariate analysis, albumin (area under the curve [AUC] = 0.77), blood urea nitrogen (AUC = 0.76), acuity level (AUC = 0.73), lactate (AUC = 0.72), and chief complaint (AUC = 0.72) were the best single predictors. For Youden's index, the model had a sensitivity of 0.77 (95% CI: 0.67-0.86) with a false positive rate of 1:9., Conclusion: A machine learning model trained on clinical measures provides proof of concept performance in predicting mortality in patients with severe obesity. This implies that such models may help to adopt specific decision support tools for this population., Competing Interests: The authors declare that they have no relevant conflict of interest., (© 2021 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Background: Research regarding the association between severe obesity and in-hospital mortality is inconsistent. We evaluated the impact of body mass index (BMI) levels on mortality in the medical wards. The analysis was performed separately before and during the COVID-19 pandemic., Methods: We retrospectively retrieved data of adult patients admitted to the medical wards at the Mount Sinai Health System in New York City. The study was conducted between January 1, 2011, to March 23, 2021. Patients were divided into two sub-cohorts: pre-COVID-19 and during-COVID-19. Patients were then clustered into groups based on BMI ranges. A multivariate logistic regression analysis compared the mortality rate among the BMI groups, before and during the pandemic., Results: Overall, 179,288 patients were admitted to the medical wards and had a recorded BMI measurement. 149,098 were admitted before the COVID-19 pandemic and 30,190 during the pandemic. Pre-pandemic, multivariate analysis showed a "J curve" between BMI and mortality. Severe obesity (BMI > 40) had an aOR of 0.8 (95% CI:0.7-1.0, p = 0.018) compared to the normal BMI group. In contrast, during the pandemic, the analysis showed a "U curve" between BMI and mortality. Severe obesity had an aOR of 1.7 (95% CI:1.3-2.4, p < 0.001) compared to the normal BMI group., Conclusions: Medical ward patients with severe obesity have a lower risk for mortality compared to patients with normal BMI. However, this does not apply during COVID-19, where obesity was a leading risk factor for mortality in the medical wards. It is important for the internal medicine physician to understand the intricacies of the association between obesity and medical ward mortality., (© 2021. The Author(s).)

Objective: Hypoalbuminaemia is an important prognostic factor. It may be associated with poor nutritional states, chronic heart and kidney disease, long-standing infection and cancer. Hypotension is a hallmark of circulatory failure. We evaluated hypoalbuminaemia and hypotension synergism as predictor of in-hospital mortality and intensive care unit (ICU) admission., Design: We retrospectively analysed emergency department (ED) visits from January 2011 to December 2019., Setting: Data were retrieved from five Mount Sinai health system hospitals, New York., Participants: We included consecutive ED patients ≥18 years with albumin measurements., Primary and Secondary Outcome Measures: Clinical outcomes were in-hospital mortality and ICU admission. The rates of these outcomes were stratified by systolic blood pressure (SBP) (<90 vs ≥90 mm Hg) and albumin levels. Variables included demographics, presenting vital signs, comorbidities (measured as ICD codes) and other common blood tests. Multivariable logistic regression models analysed the adjusted OR of different levels of albumin and SBP for predicting ICU admission and in-hospital mortality. The models were adjusted for demographics, vital signs, comorbidities and common laboratory results. Patients with albumin 3.5-4.5 g/dL and SBP ≥90 mm Hg were used as reference., Results: The cohort included 402 123 ED arrivals (27.9% of total adult ED visits). The rates of in-hospital mortality, ICU admission and overall admission were 1.7%, 8.4% and 47.1%, respectively. For SBP <90 mm Hg and albumin <2.5 g/dL, mortality and ICU admission rates were 34.0% and 40.6%, respectively; for SBP <90 mm Hg and albumin ≥2.5 g/dL 8.2% and 24.1%, respectively; for SBP ≥90 mm Hg and albumin <2.5 g/dL 11.4% and 18.6%, respectively; for SBP ≥90 mm Hg and albumin 3.5-4.5 g/dL 0.5% and 6.4%, respectively. Multivariable analysis showed that in patients with hypotension and albumin <2.5 g/dL the adjusted OR for in-hospital mortality was 37.1 (95% CI 32.3 to 42.6), and for ICU admission was 5.4 (95% CI 4.8 to 6.1)., Conclusion: Co-occurrence of hypotension and hypoalbuminaemia is associated with poor hospital outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections continue, there is a substantial need for cost-effective and large-scale testing that utilizes specimens that can be readily collected from both symptomatic and asymptomatic individuals in various community settings. Although multiple diagnostic methods utilize nasopharyngeal specimens, saliva specimens represent an attractive alternative as they can rapidly and safely be collected from different populations. While saliva has been described as an acceptable clinical matrix for the detection of SARS-CoV-2, evaluations of analytic performance across platforms for this specimen type are limited. Here, we used a novel sensitive RT-PCR/MALDI-TOF mass spectrometry-based assay (Agena MassARRAY®) to detect SARS-CoV-2 in saliva specimens. The platform demonstrated high diagnostic sensitivity and specificity when compared to matched patient upper respiratory specimens. We also evaluated the analytical sensitivity of the platform and determined the limit of detection of the assay to be 1562.5 copies/ml. Furthermore, across the five individual target components of this assay, there was a range in analytic sensitivities for each target with the N2 target being the most sensitive. Overall, this system also demonstrated comparable performance when compared to the detection of SARS-CoV-2 RNA in saliva by the cobas® 6800/8800 SARS-CoV-2 real-time RT-PCR Test (Roche). Together, we demonstrate that saliva represents an appropriate matrix for SARS-CoV-2 detection on the novel Agena system as well as on a conventional real-time RT-PCR assay. We conclude that the MassARRAY® system is a sensitive and reliable platform for SARS-CoV-2 detection in saliva, offering scalable throughput in a large variety of clinical laboratory settings., (© 2021 Wiley Periodicals LLC.)

Objective: Obesity is associated with severe coronavirus disease 2019 (COVID-19) infection. Disease severity is associated with a higher COVID-19 antibody titer. The COVID-19 antibody titer response of patients with obesity versus patients without obesity was compared., Methods: The data of individuals tested for COVID-19 serology at the Mount Sinai Health System in New York City between March 1, 2020, and December 14, 2021, were retrospectively retrieved. The primary outcome was peak antibody titer, assessed as a binary variable (1:2,880, which was the highest detected titer, versus lower than 1:2,880). In patients with a positive serology test, peak titer rates were compared between BMI groups (<18.5, 18.5 to 25, 25 to 30, 30 to 40, and ≥40 kg/m 2 ). A multivariable logistic regression model was used to analyze the independent association between different BMI groups and peak titer., Results: Overall, 39,342 individuals underwent serology testing and had BMI measurements. A positive serology test was present in 12,314 patients. Peak titer rates were associated with obesity (BMI < 18.5 [34.5%], 18.5 to 25 [29.2%], 25 to 30 [37.7%], 30 to 40 [44.7%], ≥40 [52.0%]; p < 0.001). In a multivariable analysis, severe obesity had the highest adjusted odds ratio for peak titer (95% CI: 2.1-3.0)., Conclusion: COVID-19 neutralizing antibody titer is associated with obesity. This has implications on the understanding of the role of obesity in COVID-19 severity., (© 2021 The Obesity Society.)

Background and Aim: New York City (NYC) is an epicenter of the COVID-19 pandemic in the United States. Proper triage of patients with possible COVID-19 via chief complaint is critical but not fully optimized. This study aimed to investigate the association between presentation by chief complaints and COVID-19 status., Methods: We retrospectively analyzed adult emergency department (ED) patient visits from five different NYC hospital campuses from March 1, 2020 to May 13, 2020 of patients who underwent nasopharyngeal COVID-19 RT-PCR testing. The positive and negative COVID-19 cohorts were then assessed for different chief complaints obtained from structured triage data. Sub-analysis was performed for patients older than 65 and within chief complaints with high mortality., Results: Of 11,992 ED patient visits who received COVID-19 testing, 6524/11992 (54.4%) were COVID-19 positive. 73.5% of fever, 67.7% of shortness of breath, and 65% of cough had COVID-19, but others included 57.5% of weakness/fall/altered mental status, 55.5% of glycemic control, and 51.4% of gastrointestinal symptoms. In patients over 65, 76.7% of diarrhea, 73.7% of fatigue, and 69.3% of weakness had COVID-19. 45.5% of dehydration, 40.5% of altered mental status, 27% of fall, and 24.6% of hyperglycemia patients experienced mortality., Conclusion: A novel high risk COVID-19 patient population was identified from chief complaint data, which is different from current suggested CDC guidelines, and may help triage systems to better isolate COVID-19 patients. Older patients with COVID-19 infection presented with more atypical complaints warranting special consideration. COVID-19 was associated with higher mortality in a unique group of complaints also warranting special consideration., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Inc.)

Medical knowledge is increasing at an exponential rate. At the same time, unexplained variations in practice and patient outcomes and unacceptable rates of medical errors and inefficiencies in health care delivery have emerged. Our Institute for Health Care Delivery Science (I-HDS) began in 2014 as a novel platform to conduct multidisciplinary healthcare delivery research. We followed ten strategies to develop a successful institute with excellence in methodology and strong understanding of the value of team science. Our work was organized around five hubs: 1) Quality/Process Improvement and Systematic Review, 2) Comparative Effectiveness Research, Pragmatic Clinical Trials, and Predictive Analytics, 3) Health Economics and Decision Modeling, 4) Qualitative, Survey, and Mixed Methods, and 5) Training and Mentoring. In the first 5 years of the I-HDS, we have identified opportunities for change in clinical practice through research using our health system's electronic health record (EHR) data, and designed programs to educate clinicians in the value of research to improve patient care and recognize efficiencies in processes. Testing the value of several model interventions has guided prioritization of evidence-based quality improvements. Some of the changes in practice have already been embedded in the EHR workflow successfully. Development and sustainability of the I-HDS has been fostered by a mix of internal and external funding, including philanthropic foundations. Challenges remain due to the highly competitive funding environment and changes needed to adapt the EHR to healthcare delivery research. Further stakeholder engagement and culture change working with hospital leadership and I-HDS core and affiliate members continues.

In April 2020, in light of COVID-19-related blood shortages, the US Food and Drug Administration (FDA) reduced the deferral period for men who have sex with men (MSM) from its previous duration of 1 year to 3 months.Although originally born out of necessity, the decades-old restrictions on MSM donors have been mitigated by significant advancements in HIV screening, treatment, and public education. The severity of the ongoing COVID-19 pandemic-and the urgent need for safe blood products to respond to such crises-demands an immediate reconsideration of the 3-month deferral policy for MSM.We review historical HIV testing and transmission evidence, discuss the ethical ramifications of the current deferral period, and examine the issue of noncompliance with donor deferral rules. We also propose an eligibility screening format that involves an individual risk-based screening protocol and, unlike current FDA guidelines, does not effectively exclude donors on the basis of gender identity or sexual orientation. Our policy proposal would allow historically marginalized community members to participate with dignity in the blood donation process without compromising blood donation and transfusion safety outcomes.

Background: Early reports indicate that AKI is common among patients with coronavirus disease 2019 (COVID-19) and associated with worse outcomes. However, AKI among hospitalized patients with COVID-19 in the United States is not well described., Methods: This retrospective, observational study involved a review of data from electronic health records of patients aged ≥18 years with laboratory-confirmed COVID-19 admitted to the Mount Sinai Health System from February 27 to May 30, 2020. We describe the frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aORs) with mortality., Results: Of 3993 hospitalized patients with COVID-19, AKI occurred in 1835 (46%) patients; 347 (19%) of the patients with AKI required dialysis. The proportions with stages 1, 2, or 3 AKI were 39%, 19%, and 42%, respectively. A total of 976 (24%) patients were admitted to intensive care, and 745 (76%) experienced AKI. Of the 435 patients with AKI and urine studies, 84% had proteinuria, 81% had hematuria, and 60% had leukocyturia. Independent predictors of severe AKI were CKD, men, and higher serum potassium at admission. In-hospital mortality was 50% among patients with AKI versus 8% among those without AKI (aOR, 9.2; 95% confidence interval, 7.5 to 11.3). Of survivors with AKI who were discharged, 35% had not recovered to baseline kidney function by the time of discharge. An additional 28 of 77 (36%) patients who had not recovered kidney function at discharge did so on posthospital follow-up., Conclusions: AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Of all patients with AKI, only 30% survived with recovery of kidney function by the time of discharge., (Copyright © 2021 by the American Society of Nephrology.)

Objective: Malnutrition among hospital patients, a frequent, yet under-diagnosed problem is associated with adverse impact on patient outcome and health care costs. Development of highly accurate malnutrition screening tools is, therefore, essential for its timely detection, for providing nutritional care, and for addressing the concerns related to the suboptimal predictive value of the conventional screening tools, such as the Malnutrition Universal Screening Tool (MUST). We aimed to develop a machine learning (ML) based classifier (MUST-Plus) for more accurate prediction of malnutrition., Method: A retrospective cohort with inpatient data consisting of anthropometric, lab biochemistry, clinical data, and demographics from adult (≥ 18 years) admissions at a large tertiary health care system between January 2017 and July 2018 was used. The registered dietitian (RD) nutritional assessments were used as the gold standard outcome label. The cohort was randomly split (70:30) into training and test sets. A random forest model was trained using 10-fold cross-validation on training set, and its predictive performance on test set was compared to MUST., Results: In all, 13.3% of admissions were associated with malnutrition in the test cohort. MUST-Plus provided 73.07% (95% confidence interval [CI]: 69.61%-76.33%) sensitivity, 76.89% (95% CI: 75.64%-78.11%) specificity, and 83.5% (95% CI: 82.0%-85.0%) area under the receiver operating curve (AUC). Compared to classic MUST, MUST-Plus demonstrated 30% higher sensitivity, 6% higher specificity, and 17% increased AUC., Conclusions: ML-based MUST-Plus provided superior performance in identifying malnutrition compared to the classic MUST. The tool can be used for improving the operational efficiency of RDs by timely referrals of high-risk patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with millions infected and more than 1 million fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here, on the basis of a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City, we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust immunoglobulin G antibody responses against the viral spike protein. We also show that titers are relatively stable for at least a period of about 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggest that more than 90% of seroconverters make detectable neutralizing antibody responses. These titers remain relatively stable for several months after infection., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: The COVID-19 pandemic is a global public health crisis, with over 33 million cases and 999 000 deaths worldwide. Data are needed regarding the clinical course of hospitalised patients, particularly in the USA. We aimed to compare clinical characteristic of patients with COVID-19 who had in-hospital mortality with those who were discharged alive., Design: Demographic, clinical and outcomes data for patients admitted to five Mount Sinai Health System hospitals with confirmed COVID-19 between 27 February and 2 April 2020 were identified through institutional electronic health records. We performed a retrospective comparative analysis of patients who had in-hospital mortality or were discharged alive., Setting: All patients were admitted to the Mount Sinai Health System, a large quaternary care urban hospital system., Participants: Participants over the age of 18 years were included., Primary Outcomes: We investigated in-hospital mortality during the study period., Results: A total of 2199 patients with COVID-19 were hospitalised during the study period. As of 2 April, 1121 (51%) patients remained hospitalised, and 1078 (49%) completed their hospital course. Of the latter, the overall mortality was 29%, and 36% required intensive care. The median age was 65 years overall and 75 years in those who died. Pre-existing conditions were present in 65% of those who died and 46% of those discharged. In those who died, the admission median lymphocyte percentage was 11.7%, D-dimer was 2.4 μg/mL, C reactive protein was 162 mg/L and procalcitonin was 0.44 ng/mL. In those discharged, the admission median lymphocyte percentage was 16.6%, D-dimer was 0.93 μg/mL, C reactive protein was 79 mg/L and procalcitonin was 0.09 ng/mL., Conclusions: In our cohort of hospitalised patients, requirement of intensive care and mortality were high. Patients who died typically had more pre-existing conditions and greater perturbations in inflammatory markers as compared with those who were discharged., Competing Interests: Competing interests: GNN reports grants, personal fees and non-financial support from Renalytix AI, non-financial support from Pensieve Health, personal fees from AstraZeneca, BioVie, GLG Consulting, from outside the submitted work. AL reports personal fees from Zoll, outside the submitted work. ZAF reports grants from Daiichi Sankyo, grants from Amgen, Bristol Myers Squibb and Siemens Healthineers, personal fees from Alexion, GlaxoSmithKline, Trained Therapeutix Discovery, outside the submitted work. In addition, ZAF has patents licensed to Trained Therapeutix Discovery. The other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Coronavirus disease 2019 (COVID-19), like cancer, is a complex disease with clinical phases of progression. Initially conceptualized as a respiratory disease, COVID-19 is increasingly recognized as a multi-organ and heterogeneous illness. Disease staging is a method for measuring the progression and severity of an illness using objective clinical and molecular criteria. Integral to cancer staging is "metastasis," defined as the spread of a disease-producing agent, including neoplastic cells and pathogens such as certain viruses, from the primary site to distinct anatomic locations. Staging provides valuable frameworks and benchmarks for clinical decision-making in patient management, improved prognostication, and evidence-based treatment selection., Competing Interests: Declaration of Interests C.C.-C., A.F.-B., F.K., and V.S., as part of Mount Sinai, report that the institution has licensed SARS-CoV-2 serological assays to commercial entities and have filed for patent protection for serological assays. R.S. reports to be associated with SEMA4. P.S.-S. is the chief executive officer and majority shareholder of both ImmunityBio, Inc., and NantKwest, Inc., and is developing a qLAMP assay., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: COVID-19 has infected millions of people worldwide and is responsible for several hundred thousand fatalities. The COVID-19 pandemic has necessitated thoughtful resource allocation and early identification of high-risk patients. However, effective methods to meet these needs are lacking., Objective: The aims of this study were to analyze the electronic health records (EHRs) of patients who tested positive for COVID-19 and were admitted to hospitals in the Mount Sinai Health System in New York City; to develop machine learning models for making predictions about the hospital course of the patients over clinically meaningful time horizons based on patient characteristics at admission; and to assess the performance of these models at multiple hospitals and time points., Methods: We used Extreme Gradient Boosting (XGBoost) and baseline comparator models to predict in-hospital mortality and critical events at time windows of 3, 5, 7, and 10 days from admission. Our study population included harmonized EHR data from five hospitals in New York City for 4098 COVID-19-positive patients admitted from March 15 to May 22, 2020. The models were first trained on patients from a single hospital (n=1514) before or on May 1, externally validated on patients from four other hospitals (n=2201) before or on May 1, and prospectively validated on all patients after May 1 (n=383). Finally, we established model interpretability to identify and rank variables that drive model predictions., Results: Upon cross-validation, the XGBoost classifier outperformed baseline models, with an area under the receiver operating characteristic curve (AUC-ROC) for mortality of 0.89 at 3 days, 0.85 at 5 and 7 days, and 0.84 at 10 days. XGBoost also performed well for critical event prediction, with an AUC-ROC of 0.80 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. In external validation, XGBoost achieved an AUC-ROC of 0.88 at 3 days, 0.86 at 5 days, 0.86 at 7 days, and 0.84 at 10 days for mortality prediction. Similarly, the unimputed XGBoost model achieved an AUC-ROC of 0.78 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. Trends in performance on prospective validation sets were similar. At 7 days, acute kidney injury on admission, elevated LDH, tachypnea, and hyperglycemia were the strongest drivers of critical event prediction, while higher age, anion gap, and C-reactive protein were the strongest drivers of mortality prediction., Conclusions: We externally and prospectively trained and validated machine learning models for mortality and critical events for patients with COVID-19 at different time horizons. These models identified at-risk patients and uncovered underlying relationships that predicted outcomes., (©Akhil Vaid, Sulaiman Somani, Adam J Russak, Jessica K De Freitas, Fayzan F Chaudhry, Ishan Paranjpe, Kipp W Johnson, Samuel J Lee, Riccardo Miotto, Felix Richter, Shan Zhao, Noam D Beckmann, Nidhi Naik, Arash Kia, Prem Timsina, Anuradha Lala, Manish Paranjpe, Eddye Golden, Matteo Danieletto, Manbir Singh, Dara Meyer, Paul F O'Reilly, Laura Huckins, Patricia Kovatch, Joseph Finkelstein, Robert M. Freeman, Edgar Argulian, Andrew Kasarskis, Bethany Percha, Judith A Aberg, Emilia Bagiella, Carol R Horowitz, Barbara Murphy, Eric J Nestler, Eric E Schadt, Judy H Cho, Carlos Cordon-Cardo, Valentin Fuster, Dennis S Charney, David L Reich, Erwin P Bottinger, Matthew A Levin, Jagat Narula, Zahi A Fayad, Allan C Just, Alexander W Charney, Girish N Nadkarni, Benjamin S Glicksberg. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 06.11.2020.)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new human disease with few effective treatments 1 . Convalescent plasma, donated by persons who have recovered from COVID-19, is the acellular component of blood that contains antibodies, including those that specifically recognize SARS-CoV-2. These antibodies, when transfused into patients infected with SARS-CoV-2, are thought to exert an antiviral effect, suppressing virus replication before patients have mounted their own humoral immune responses 2,3 . Virus-specific antibodies from recovered persons are often the first available therapy for an emerging infectious disease, a stopgap treatment while new antivirals and vaccines are being developed 1,2 . This retrospective, propensity score-matched case-control study assessed the effectiveness of convalescent plasma therapy in 39 patients with severe or life-threatening COVID-19 at The Mount Sinai Hospital in New York City. Oxygen requirements on day 14 after transfusion worsened in 17.9% of plasma recipients versus 28.2% of propensity score-matched controls who were hospitalized with COVID-19 (adjusted odds ratio (OR), 0.86; 95% confidence interval (CI), 0.75-0.98; chi-square test P value = 0.025). Survival also improved in plasma recipients (adjusted hazard ratio (HR), 0.34; 95% CI, 0.13-0.89; chi-square test P = 0.027). Convalescent plasma is potentially effective against COVID-19, but adequately powered, randomized controlled trials are needed.

Purpose: To investigate whether sarcoidosis patients infected with SARS-CoV-2 are at risk for adverse disease outcomes., Study Design and Methods: This retrospective study was conducted in five hospitals within the Mount Sinai Health System during March 1, 2020 to July 29, 2020. All patients diagnosed with COVID-19 were included in the study. We identified sarcoidosis patients who met diagnostic criteria for sarcoidosis according to accepted guidelines. An adverse disease outcome was defined as the presence of intubation and mechanical ventilation or in-hospital mortality. In sarcoidosis patients, we reported (when available) the results of pulmonary function testing measured within 3 years prior to the time of SARS‑CoV‑2 infection. A multivariable logistic regression model was used to generate an adjusted odds ratio (aOR) to evaluate sarcoidosis as a risk factor for an adverse outcome. The same model was used to analyze sarcoidosis patients with moderate and/or severe impairment in pulmonary function., Results: The study included 7337 patients, 37 of whom (0.5%) had sarcoidosis. The crude rate of developing an adverse outcome was significantly higher in patients with moderately and/or severely impaired pulmonary function (9/14 vs. 3/23, p = 0.003). While the diagnosis of sarcoidosis was not independently associated with risk of an adverse event, (aOR 1.8, 95% CI 0.9-3.6), the diagnosis of sarcoidosis in patients with moderately and/or severely impaired pulmonary function was associated with an adverse outcome (aOR 7.8, 95% CI 2.4-25.8)., Conclusion: Moderate or severe impairment in pulmonary function is associated with mortality in sarcoidosis patients infected with SARS‑CoV‑2.

Objectives: To develop and validate a model for prediction of near-term in-hospital mortality among patients with COVID-19 by application of a machine learning (ML) algorithm on time-series inpatient data from electronic health records., Methods: A cohort comprised of 567 patients with COVID-19 at a large acute care healthcare system between 10 February 2020 and 7 April 2020 observed until either death or discharge. Random forest (RF) model was developed on randomly drawn 70% of the cohort (training set) and its performance was evaluated on the rest of 30% (the test set). The outcome variable was in-hospital mortality within 20-84 hours from the time of prediction. Input features included patients' vital signs, laboratory data and ECG results., Results: Patients had a median age of 60.2 years (IQR 26.2 years); 54.1% were men. In-hospital mortality rate was 17.0% and overall median time to death was 6.5 days (range 1.3-23.0 days). In the test set, the RF classifier yielded a sensitivity of 87.8% (95% CI: 78.2% to 94.3%), specificity of 60.6% (95% CI: 55.2% to 65.8%), accuracy of 65.5% (95% CI: 60.7% to 70.0%), area under the receiver operating characteristic curve of 85.5% (95% CI: 80.8% to 90.2%) and area under the precision recall curve of 64.4% (95% CI: 53.5% to 75.3%)., Conclusions: Our ML-based approach can be used to analyse electronic health record data and reliably predict near-term mortality prediction. Using such a model in hospitals could help improve care, thereby better aligning clinical decisions with prognosis in critically ill patients with COVID-19., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Coronavirus disease 2019 (COVID-19) continues to spread, and younger patients are also being critically affected. This study analyzed obesity as an independent risk factor for mortality in hospitalized patients younger than 50., Methods: This study retrospectively analyzed data of patients with COVID-19 who were hospitalized to a large academic hospital system in New York City between March 1, 2020, and May 17, 2020. Data included demographics, comorbidities, BMI, and smoking status. Obesity groups included the following: BMI of 30 to < 40 kg/m 2 and BMI ≥ 40 kg/m 2 . Multivariable logistic regression models identified variables independently associated with mortality in patients younger and older than 50., Results: Overall, 3,406 patients were included; 572 (17.0%) patients were younger than 50. In the younger age group, 60 (10.5%) patients died. In the older age group, 1,076 (38.0%) patients died. For the younger population, BMI ≥ 40 was independently associated with mortality (adjusted odds ratio 5.1; 95% CI: 2.3-11.1). For the older population, BMI ≥ 40 was also independently associated with mortality to a lesser extent (adjusted odds ratio 1.6; 95% CI: 1.2-2.3)., Conclusions: This study demonstrates that hospitalized patients younger than 50 with severe obesity are more likely to die of COVID-19. This is particularly relevant in the Western world, where obesity rates are high., (© 2020 The Obesity Society.)

Objectives: Approximately 20-30% of patients with COVID-19 require hospitalization, and 5-12% may require critical care in an intensive care unit (ICU). A rapid surge in cases of severe COVID-19 will lead to a corresponding surge in demand for ICU care. Because of constraints on resources, frontline healthcare workers may be unable to provide the frequent monitoring and assessment required for all patients at high risk of clinical deterioration. We developed a machine learning-based risk prioritization tool that predicts ICU transfer within 24 h, seeking to facilitate efficient use of care providers' efforts and help hospitals plan their flow of operations., Methods: A retrospective cohort was comprised of non-ICU COVID-19 admissions at a large acute care health system between 26 February and 18 April 2020. Time series data, including vital signs, nursing assessments, laboratory data, and electrocardiograms, were used as input variables for training a random forest (RF) model. The cohort was randomly split (70:30) into training and test sets. The RF model was trained using 10-fold cross-validation on the training set, and its predictive performance on the test set was then evaluated., Results: The cohort consisted of 1987 unique patients diagnosed with COVID-19 and admitted to non-ICU units of the hospital. The median time to ICU transfer was 2.45 days from the time of admission. Compared to actual admissions, the tool had 72.8% (95% CI: 63.2-81.1%) sensitivity, 76.3% (95% CI: 74.7-77.9%) specificity, 76.2% (95% CI: 74.6-77.7%) accuracy, and 79.9% (95% CI: 75.2-84.6%) area under the receiver operating characteristics curve., Conclusions: A ML-based prediction model can be used as a screening tool to identify patients at risk of imminent ICU transfer within 24 h. This tool could improve the management of hospital resources and patient-throughput planning, thus delivering more effective care to patients hospitalized with COVID-19.

Background: Falls are the most common adverse events of hospitalized adults. Traditional validated assessment tools have limited ability to accurately detect patients at high risk for falls. The researchers aim to develop an automated comprehensive risk score to enhance the identification of patients at high risk for falls and examine its effectiveness., Methods: The enhanced fall algorithm (EFA) was developed from 171,515 hospitalizations and 2,659 falls, in an academic medical center, using hierarchical logistic regression. Routine nursing assessments, labs, medications, demographics, and patients' location during their hospitalization were gathered from the electronic health record (EHR)., Results: The fall rate was 2.8 per 1,000 patient-days. Morse fall score was the strongest predictor of falls (odds ratio = 7.16, 95% confidence interval = 6.48-7.91), with a model discrimination c-statistic of 0.687. By adding patient demographics, chronic conditions, lab values, and medications, and controlling for patient clustering within units, predication was enhanced and model discrimination increased to 0.805. By applying the enhanced model, we observed redistribution of patient by risk: low-risk group increased from 52.8% to 66.5%, and the high-risk group decreased from 28.0% to 16.2%, with an increase of fall detection from 3.1% to 5.1%., Conclusion: The EFA redistributes and identifies patients at high risk more accurately than the Morse score alone, decreasing the population of high-risk patients without increasing the rate of falls over time. The EFA requires no addition data collection and automatically updates the patient's fall risk based on new inputs in the EHR., (Copyright © 2020 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Objective: The study objective was to determine whether targeted therapy to optimize cerebral oxygenation is associated with improved neurocognitive and perioperative outcomes., Methods: In a prospective trial, intraoperative cerebral oximetry monitoring using bilateral forehead probes was performed in cardiac surgical patients who were randomly assigned to an intervention group in which episodes of cerebral oxygen desaturation (<60% for >60 consecutive seconds at either probe) triggered an intervention protocol or a control group in which the cerebral oximetry data were hidden from the clinical team, and no intervention protocol was applied. Cognitive testing was performed preoperatively and at postoperative months 3 and 6; domains studied were response speed, processing speed, attention, and memory. Perioperative outcomes studied were death, hospital length of stay, intensive care unit length of stay, postoperative day of extubation, time on mechanical ventilation, intensive care unit delirium, Sequential Organ Failure Assessment on intensive care unit admission, and intensive care unit blood transfusion., Results: Group mean memory change scores were significantly better in the intervention group at 6 months (0.60 [standard error, 0.30] vs -0.17 [standard error, 0.33], adjusted P = .008). However, presence, duration, and severity of cerebral desaturation were not associated with cognitive change scores. Perioperative outcomes did not differ between the intervention and control groups., Conclusions: Targeted therapy to optimize cerebral oxygenation was associated with better memory outcome in a group of cardiac surgical patients. Some aspects of the protocol other than desaturation duration and severity contributed to the observed neuroprotective effect., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Early detection of patients at risk for clinical deterioration is crucial for timely intervention. Traditional detection systems rely on a limited set of variables and are unable to predict the time of decline. We describe a machine learning model called MEWS++ that enables the identification of patients at risk of escalation of care or death six hours prior to the event. A retrospective single-center cohort study was conducted from July 2011 to July 2017 of adult (age > 18) inpatients excluding psychiatric, parturient, and hospice patients. Three machine learning models were trained and tested: random forest (RF), linear support vector machine, and logistic regression. We compared the models' performance to the traditional Modified Early Warning Score (MEWS) using sensitivity, specificity, and Area Under the Curve for Receiver Operating Characteristic (AUC-ROC) and Precision-Recall curves (AUC-PR). The primary outcome was escalation of care from a floor bed to an intensive care or step-down unit, or death, within 6 h. A total of 96,645 patients with 157,984 hospital encounters and 244,343 bed movements were included. Overall rate of escalation or death was 3.4%. The RF model had the best performance with sensitivity 81.6%, specificity 75.5%, AUC-ROC of 0.85, and AUC-PR of 0.37. Compared to traditional MEWS, sensitivity increased 37%, specificity increased 11%, and AUC-ROC increased 14%. This study found that using machine learning and readily available clinical data, clinical deterioration or death can be predicted 6 h prior to the event. The model we developed can warn of patient deterioration hours before the event, thus helping make timely clinical decisions.

Previous studies demonstrated a higher COVID-19 fatality rate in men. The aim of this study was to compare age and comorbidities between women and men who died from COVID-19. We retrospectively analyzed data of COVID-19 patients hospitalized to a large academic hospital system in New York City between March 1 and May 9, 2020. We used a multivariable logistic regression model to identify independently significant variables associated with gender in patients who died from COVID-19. The model was adjusted for age and comorbidities known to be associated with COVID-19 mortality. We identified 6760 patients diagnosed with COVID-19. Of these patients, 3018/6760 (44.6%) were women. The mortality rate was higher for men (women 18.2% vs. men 20.6%, p  = 0.039). Of the patients who died, women were on average 5 years older than men (woman 77.4 ± 12.7 vs. men 72.4 ± 13.0, p < 0.001). In the multivariable model, cardiovascular comorbidities were not significantly different between women and men. Chronic kidney disease (aOR for women 0.7, 95% CI 0.5-0.9) and smoking (aOR for women 0.7, 95% CI 0.5-0.9) were more common in men. Age decile (aOR for women 1.4, 95% CI 1.3-1.6) and obesity (aOR for women 2.3, 95% CI 1.8-3.0) were higher in women. This study demonstrates that women who died of COVID-19 showed a similar cardiovascular disease profile as men. Yet, they are 5 years older than men. Investigating the gender impacts of COVID-19 is an important part of understanding the disease behavior., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© Springer Nature Switzerland AG 2020.)

Purpose: Several factors lead to medication non-adherence after hospital discharge. Hospitals and pharmacies have implemented bedside medication delivery (BMD) programs for patients, in an attempt to reduce barriers and improve medication adherence. Here, we provide a critical review of the literature on these programs., Data Sources: We conducted a literature search on BMD programs in PubMed, Google Scholar, Scopus and a general Google search using these keywords: 'medication delivery bedside', 'discharge medication delivery', 'meds to bedside' and 'meds to beds'., Study Selection: We identified 10 reports and include data from all reports., Data Extraction: Data on study characteristics and settings were extracted along with four outcomes: medication error, patient satisfaction, 30-day hospital readmission and visits to the emergency department., Results of Data Synthesis: Of the 10 reports, only 4 were peer-reviewed publications; others were reported in the lay press. Outcomes were reported in both qualitative and quantitative terms. Less than half of reports provided quantitative data on 30-day readmission and patient satisfaction. Others suggested qualitative improvement in these outcomes but did not provide data or specific details. None reported outcomes of their programs beyond 30 days., Conclusion: We highlight the need for increased use of optimal program design and more rigorous evaluations of the impact of BMD programs. We also provide guidelines on the types of evaluations that are likely needed and encourage improved reporting., (© The Author(s) 2019. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Worldwide, over 14% of individuals hospitalized for psychiatric reasons have readmissions to hospitals within 30 days after discharge. Predicting patients at risk and leveraging accelerated interventions can reduce the rates of early readmission, a negative clinical outcome (i.e., a treatment failure) that affects the quality of life of patient. To implement individualized interventions, it is necessary to predict those individuals at highest risk for 30-day readmission. In this study, our aim was to conduct a data-driven investigation to find the pharmacological factors influencing 30-day all-cause, intra- and interdepartmental readmissions after an index psychiatric admission, using the compendium of prescription data (prescriptome) from electronic medical records (EMR)., Methods: The data scientists in the project received a deidentified database from the Mount Sinai Data Warehouse, which was used to perform all analyses. Data was stored in a secured MySQL database, normalized and indexed using a unique hexadecimal identifier associated with the data for psychiatric illness visits. We used Bayesian logistic regression models to evaluate the association of prescription data with 30-day readmission risk. We constructed individual models and compiled results after adjusting for covariates, including drug exposure, age, and gender. We also performed digital comorbidity survey using EMR data combined with the estimation of shared genetic architecture using genomic annotations to disease phenotypes., Results: Using an automated, data-driven approach, we identified prescription medications, side effects (primary side effects), and drug-drug interaction-induced side effects (secondary side effects) associated with readmission risk in a cohort of 1275 patients using prescriptome analytics. In our study, we identified 28 drugs associated with risk for readmission among psychiatric patients. Based on prescription data, Pravastatin had the highest risk of readmission (OR = 13.10; 95% CI (2.82, 60.8)). We also identified enrichment of primary side effects (n = 4006) and secondary side effects (n = 36) induced by prescription drugs in the subset of readmitted patients (n = 89) compared to the non-readmitted subgroup (n = 1186). Digital comorbidity analyses and shared genetic analyses further reveals that cardiovascular disease and psychiatric conditions are comorbid and share functional gene modules (cardiomyopathy and anxiety disorder: shared genes (n = 37; P = 1.06815E-06))., Conclusions: Large scale prescriptome data is now available from EMRs and accessible for analytics that could improve healthcare outcomes. Such analyses could also drive hypothesis and data-driven research. In this study, we explored the utility of prescriptome data to identify factors driving readmission in a psychiatric cohort. Converging digital health data from EMRs and systems biology investigations reveal a subset of patient populations that have significant comorbidities with cardiovascular diseases are more likely to be readmitted. Further, the genetic architecture of psychiatric illness also suggests overlap with cardiovascular diseases. In summary, assessment of medications, side effects, and drug-drug interactions in a clinical setting as well as genomic information using a data mining approach could help to find factors that could help to lower readmission rates in patients with mental illness.