Derivation and external validation of a simple risk score to predict in-hospital mortality in patients hospitalized for COVID-19: A multicenter retrospective cohort study

ABSTRACT: As severe acute respiratory syndrome coronavirus 2 continues to spread, easy-to-use risk models that predict hospital mortality can assist in clinical decision making and triage. We aimed to develop a risk score model for in-hospital mortality in patients hospitalized with 2019 novel coronavirus (COVID-19) that was robust across hospitals and used clinical factors that are readily available and measured standardly across hospitals. In this retrospective observational study, we developed a risk score model using data collected by trained abstractors for patients in 20 diverse hospitals across the state of Michigan (Mi-COVID19) who were discharged between March 5, 2020 and August 14, 2020. Patients who tested positive for severe acute respiratory syndrome coronavirus 2 during hospitalization or were discharged with an ICD-10 code for COVID-19 (U07.1) were included. We employed an iterative forward selection approach to consider the inclusion of 145 potential risk factors available at hospital presentation. Model performance was externally validated with patients from 19 hospitals in the Mi-COVID19 registry not used in model development. We shared the model in an easy-to-use online application that allows the user to predict in-hospital mortality risk for a patient if they have any subset of the variables in the final model. Two thousand one hundred and ninety-three patients in the Mi-COVID19 registry met our inclusion criteria. The derivation and validation sets ultimately included 1690 and 398 patients, respectively, with mortality rates of 19.6% and 18.6%, respectively. The average age of participants in the study after exclusions was 64 years old, and the participants were 48% female, 49% Black, and 87% non-Hispanic. Our final model includes the patient\u27s age, first recorded respiratory rate, first recorded pulse oximetry, highest creatinine level on day of presentation, and hospital\u27s COVID-19 mortality rate. No other factors showed sufficient incremental model improvement to warrant inclusion. The area under the receiver operating characteristics curve for the derivation and validation sets were .796 (95% confidence interval, .767-.826) and .829 (95% confidence interval, .782-.876) respectively. We conclude that the risk of in-hospital mortality in COVID-19 patients can be reliably estimated using a few factors, which are standardly measured and available to physicians very early in a hospital encounter

Risk factors and outcomes associated with community-onset and hospital-acquired coinfection in patients hospitalized for coronavirus disease 2019 (COVID-19): A multihospital cohort study

BACKGROUND: We sought to determine the incidence of community-onset and hospital-acquired coinfection in patients hospitalized with coronavirus disease 2019 (COVID-19) and to evaluate associated predictors and outcomes. METHODS: In this multicenter retrospective cohort study of patients hospitalized for COVID-19 from March 2020 to August 2020 across 38 Michigan hospitals, we assessed prevalence, predictors, and outcomes of community-onset and hospital-acquired coinfections. In-hospital and 60-day mortality, readmission, discharge to long-term care facility (LTCF), and mechanical ventilation duration were assessed for patients with versus without coinfection. RESULTS: Of 2,205 patients with COVID-19, 141 (6.4%) had a coinfection: 3.0% community onset and 3.4% hospital acquired. Of patients without coinfection, 64.9% received antibiotics. Community-onset coinfection predictors included admission from an LTCF (OR, 3.98; 95% CI, 2.34-6.76; P \u3c .001) and admission to intensive care (OR, 4.34; 95% CI, 2.87-6.55; P \u3c .001). Hospital-acquired coinfection predictors included fever (OR, 2.46; 95% CI, 1.15-5.27; P = .02) and advanced respiratory support (OR, 40.72; 95% CI, 13.49-122.93; P \u3c .001). Patients with (vs without) community-onset coinfection had longer mechanical ventilation (OR, 3.31; 95% CI, 1.67-6.56; P = .001) and higher in-hospital mortality (OR, 1.90; 95% CI, 1.06-3.40; P = .03) and 60-day mortality (OR, 1.86; 95% CI, 1.05-3.29; P = .03). Patients with (vs without) hospital-acquired coinfection had higher discharge to LTCF (OR, 8.48; 95% CI, 3.30-21.76; P \u3c .001), in-hospital mortality (OR, 4.17; 95% CI, 2.37-7.33; P ≤ .001), and 60-day mortality (OR, 3.66; 95% CI, 2.11-6.33; P ≤ .001). CONCLUSION: Despite community-onset and hospital-acquired coinfection being uncommon, most patients hospitalized with COVID-19 received antibiotics. Admission from LTCF and to ICU were associated with increased risk of community-onset coinfection. Future studies should prospectively validate predictors of COVID-19 coinfection to facilitate the reduction of antibiotic use

Characteristics of intensive care units in Michigan: Not an open and closed case

OBJECTIVE: Delivery of critical care by intensivists has been recommended by several groups. Our objective was to understand the delivery of critical care physician services in Michigan and the role of intensivists and nonintensivist providers in providing care. DESIGN: Descriptive questionnaire. PARTICIPANTS AND SETTING: Intensive care unit (ICU) directors and nurse managers at 96 sites, representing 115 ICUs from 72 hospitals in Michigan. MEASUREMENTS AND RESULTS: The primary outcome measure was the percentage of sites utilizing a closed vs. an open model of ICU care. Secondary outcome measures included the percentage of ICUs utilizing a high-intensity service model, hospital size, ICU size, type of clinician providing care, and clinical activities performed. Twenty-four (25%) sites used a closed model of intensive care, while 72 (75%) had an open model of care. Hospitals with closed ICUs were larger and had larger ICUs than sites with open ICUs ( P < 0.05). Hospitalists serving as attending physicians were strongly associated with an open ICU (odds ratio [OR] = 12.2; 95% confidence interval [CI] = 2.5-60.2), as was the absence of intensivists in the group (OR = 12.2; 95%CI = 1.4-105.8), while ICU and hospital size were not associated. At 18 sites (20%) all attendings were board certified in Critical Care. Sixty sites had less than 50% board-certified attending physicians. CONCLUSIONS: The closed intensivist-led model of intensive care delivery is not in widespread use in Michigan. In the absence of intensivists, alternate models of care, including the hospitalist model, are frequently used. Journal of Hospital Medicine 2010;5:4–9. © 2010 Society of Hospital Medicine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64903/1/567_ftp.pd

The Inactivation Principle: Mathematical Solutions Minimizing the Absolute Work and Biological Implications for the Planning of Arm Movements

An important question in the literature focusing on motor control is to determine which laws drive biological limb movements. This question has prompted numerous investigations analyzing arm movements in both humans and monkeys. Many theories assume that among all possible movements the one actually performed satisfies an optimality criterion. In the framework of optimal control theory, a first approach is to choose a cost function and test whether the proposed model fits with experimental data. A second approach (generally considered as the more difficult) is to infer the cost function from behavioral data. The cost proposed here includes a term called the absolute work of forces, reflecting the mechanical energy expenditure. Contrary to most investigations studying optimality principles of arm movements, this model has the particularity of using a cost function that is not smooth. First, a mathematical theory related to both direct and inverse optimal control approaches is presented. The first theoretical result is the Inactivation Principle, according to which minimizing a term similar to the absolute work implies simultaneous inactivation of agonistic and antagonistic muscles acting on a single joint, near the time of peak velocity. The second theoretical result is that, conversely, the presence of non-smoothness in the cost function is a necessary condition for the existence of such inactivation. Second, during an experimental study, participants were asked to perform fast vertical arm movements with one, two, and three degrees of freedom. Observed trajectories, velocity profiles, and final postures were accurately simulated by the model. In accordance, electromyographic signals showed brief simultaneous inactivation of opposing muscles during movements. Thus, assuming that human movements are optimal with respect to a certain integral cost, the minimization of an absolute-work-like cost is supported by experimental observations. Such types of optimality criteria may be applied to a large range of biological movements

Long-term efficacy of botulinum toxin A for treatment of blepharospasm,hemifacial spasm, and spastic entropion: a multicentre study using two drug-dose escalation indexes

PURPOSE: To investigate the long-term effectiveness and safety of botulinum neurotoxin A (BoNT-A) treatment in patients with blepharospasm (BEB), hemifacial spasm (HFS), and entropion (EN) and to use for the first time two modified indexes, 'botulin toxin escalation index-U' (BEI-U) and 'botulin toxin escalation index percentage' (BEI-%), in the dose-escalation evaluation. METHODS: All patients in this multicentre study were followed for at least 10 years and main outcomes were clinical efficacy, duration of relief, BEI-U and BEI-%, and frequency of adverse events. RESULTS: BEB, HFS, and EN patients received a mean BoNT-A dose with a significant inter-group difference (P<0.0005, respectively). The mean (+/-SD) effect duration was statistically different (P=0.009) among three patient groups. Regarding the BoNT-A escalation indexes, the mean (+/-SD) values of BEI-U and BEI-% were statistically different (P=0.035 and 0.047, respectively) among the three groups. In BEB patients, the BEI-% was significantly increased in younger compared with older patients (P=0.008). The most frequent adverse events were upper lid ptosis, diplopia, ecchymosis, and localized bruising. CONCLUSIONS: This long-term multicentre study supports a high efficacy and good safety profile of BoNT-A for treatment of BEB, HFS, and EN. The BEI indexes indicate a significantly greater BoNT-A-dose escalation for BEB patients compared with HFS or EN patients and a significantly greater BEI-% in younger vsolder BEB patients. These results confirm a greater efficacy in the elderly and provide a framework for long-term studies with a more flexible and reliable evaluation of drug-dose escalation

Movement Timing and Invariance Arise from Several Geometries

Human movements show several prominent features; movement duration is nearly independent of movement size (the isochrony principle), instantaneous speed depends on movement curvature (captured by the 2/3 power law), and complex movements are composed of simpler elements (movement compositionality). No existing theory can successfully account for all of these features, and the nature of the underlying motion primitives is still unknown. Also unknown is how the brain selects movement duration. Here we present a new theory of movement timing based on geometrical invariance. We propose that movement duration and compositionality arise from cooperation among Euclidian, equi-affine and full affine geometries. Each geometry posses a canonical measure of distance along curves, an invariant arc-length parameter. We suggest that for continuous movements, the actual movement duration reflects a particular tensorial mixture of these canonical parameters. Near geometrical singularities, specific combinations are selected to compensate for time expansion or compression in individual parameters. The theory was mathematically formulated using Cartan's moving frame method. Its predictions were tested on three data sets: drawings of elliptical curves, locomotion and drawing trajectories of complex figural forms (cloverleaves, lemniscates and limaçons, with varying ratios between the sizes of the large versus the small loops). Our theory accounted well for the kinematic and temporal features of these movements, in most cases better than the constrained Minimum Jerk model, even when taking into account the number of estimated free parameters. During both drawing and locomotion equi-affine geometry was the most dominant geometry, with affine geometry second most important during drawing; Euclidian geometry was second most important during locomotion. We further discuss the implications of this theory: the origin of the dominance of equi-affine geometry, the possibility that the brain uses different mixtures of these geometries to encode movement duration and speed, and the ontogeny of such representations

Approaches to Missing Data Inference Results from CaPSURE: An Observational Study of Patients with Prostate Cancer

Objective: There are multiple reasons for missing data in observational studies; excluding patients with missing data can lead to significant bias. In this study, we evaluated several methods for assigning missing values to health service utilisation. Design and setting: Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) is a US national database of men with prostate cancer. Physician visits and diagnostic tests for 342 patients newly diagnosed with prostate cancer were evaluated. Patients and participants: Patients were followed for a full year (observed data, n = 228) and patients with incomplete data (predicted data, n = 114) were included. Interventions: We used the following approaches for imputing missing data: assigning the group mean, a time-specific mean, a patient-specific mean, a stratified mean (by age, localised disease and insurance status) and carrying the last observation forward and/or backward. Main outcome measures and results: All prediction strategies resulted in higher estimates (19.3 to 23.1) for annual physician visits than was observed (17.1 +- 15.5), and differences were statistically significant for both the last observation carried forward (23.1 +- 15.5) and the patient's individual mean (22.7 +- 36.1) when predicting physician visits. The same strategies had higher predicted values for x-rays (1.8 +- 5.1 and 1.8 +- 4.4 vs 1.1 +- 1.9 for the observed group), although the last observation carried forward was not statistically different from the observed value. Conclusions: We were unable to identify a single optimal strategy. However, imputation from individual means and the last observation carried forward methods did not perform as well as the other strategies. While the differences observed in this study were small, we anticipate that with increased length of follow-up and more dropouts, there would be greater differences among strategies.Pharmacoeconomics, Prostate-cancer, Resource-use, Clinical-trial-design, Statistics

Impact of Early Corticosteroids on Preventing Clinical Deterioration in Non-critically Ill Patients Hospitalized with COVID-19: A Multi-hospital Cohort Study

Abstract Introduction While guidelines stronglyrecommend dexamethasone in critical COVID-19, the optimal threshold to initiate corticosteroids in non-critically ill patients with COVID-19 remains unclear. Using data from a state-wide COVID-19 registry, we evaluated the effectiveness of early corticosteroids for preventing clinical deterioration among non-critically ill patients hospitalized for COVID-19 and receiving non-invasive oxygen therapy. Methods This was a target trial using observational data from patients hospitalized for COVID-19 at 39 hospitals participating in the MI-COVID19 registry between March 16, 2020 and August 24, 2020. We studied the impact of corticosteroids initiated within 2 calendar days of hospitalization (“early steroids”) versus no early steroids among non-ICU patients with laboratory-confirmed SARS-CoV2 receiving non-invasive supplemental oxygen therapy. Our primary outcome was a composite of in-hospital mortality, transfer to intensive care, and receipt of invasive mechanical ventilation. We used inverse probability of treatment weighting (IPTW) and propensity score-weighted regression to measure the association of early steroids and outcomes. Results Among 1002 patients meeting study criteria, 231 (23.1%) received early steroids. After IPTW, to balance potential confounders between the treatment groups, early steroids were not associated with a decrease in the composite outcome (aOR 1.1, 95%CI 0.8–1.6) or in any components of the primary outcome. Conclusion We found no evidence that early corticosteroid therapy prevents clinical deterioration among hospitalized non-critically ill COVID-19 patients receiving non-invasive oxygen therapy. Further studies are needed to determine the optimal threshold for initiating corticosteroids in this population.http://deepblue.lib.umich.edu/bitstream/2027.42/173969/1/40121_2022_Article_615.pd