Performance of Early Warning Scoring Systems Regarding Adverse Events of Unanticipated Clinical Deterioration in Complementary and Alternative Medicine Hospitals.

PURPOSE: This study aims to examine the performance of early warning scoring systems regarding adverse events of unanticipated clinical deterioration in complementary and alternative medicine hospitals. METHODS: A medical record review of 500 patients from 5-year patient data in two traditional Korean medicine hospitals was conducted. Unanticipated clinical deterioration events included unexpected in-hospital mortality, cardiac arrest, and unplanned transfers to acute-care conventional medicine hospitals. Scores of the Modified Early Warning Score (MEWS), National Early Warning Score (NEWS), and National Early Warning Score 2 (NEWS2) were calculated. Their performance was evaluated by calculating areas under the receiver-operating characteristic curve for the event occurrence. Multiple logistic regression analyses were performed to determine the factors associated with event occurrence. RESULTS: The incidence of unanticipated clinical deterioration events was 1.1% (225/21101). The area under the curve of MEWS, NEWS, and NEWS2 was .68, .72, and .72 at 24 hours before the events, respectively. NEWS and NEWS2, with almost the same performance, were superior to MEWS (p = .009). After adjusting for other variables, patients at low-medium risk (OR = 3.28; 95% CI = 1.02-10.55) and those at medium and high risk (OR = 25.03; 95% CI = 2.78-225.46) on NEWS2 scores were more likely to experience unanticipated clinical deterioration than those at low risk. Other factors associated with the event occurrence included frailty risk scores, clinical worry scores, primary medical diagnosis, prescribed medicine administration, acupuncture treatment, and clinical department. CONCLUSIONS: The three early warning scores demonstrated moderate-to-fair performance for clinical deterioration events. NEWS2 can be used for early identification of patients at high risk of deterioration in complementary and alternative medicine hospitals. Additionally, patient, care, and system factors need to be considered to improve patient safety.

Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution.

Background: Managing the inflammatory response to SARS-Cov-2 could prevent respiratory insufficiency. Cytokine profiles could identify cases at risk of severe disease. Methods: We designed a randomized phase II clinical trial to determine whether the combination of ruxolitinib (5 mg twice a day for 7 days followed by 10 mg BID for 7 days) plus simvastatin (40 mg once a day for 14 days), could reduce the incidence of respiratory insufficiency in COVID-19. 48 cytokines were correlated with clinical outcome. Participants: Patients admitted due to COVID-19 infection with mild disease. Results: Up to 92 were included. Mean age was 64 ± 17, and 28 (30%) were female. 11 (22%) patients in the control arm and 6 (12%) in the experimental arm reached an OSCI grade of 5 or higher (p = 0.29). Unsupervised analysis of cytokines detected two clusters (CL-1 and CL-2). CL-1 presented a higher risk of clinical deterioration vs CL-2 (13 [33%] vs 2 [6%] cases, p = 0.009) and death (5 [11%] vs 0 cases, p = 0.059). Supervised Machine Learning (ML) analysis led to a model that predicted patient deterioration 48h before occurrence with a 85% accuracy. Conclusions: Ruxolitinib plus simvastatin did not impact the outcome of COVID-19. Cytokine profiling identified patients at risk of severe COVID-19 and predicted clinical deterioration. Trial registration: https://clinicaltrials.gov/, identifier NCT04348695.

Microvascular injuries, secondary edema, and inconsistencies in lung vascularization between affected and nonaffected pulmonary segments of non-critically ill hospitalized COVID-19 patients presenting with clinical deterioration.

PURPOSE: We aimed to better understand the pathophysiology of SARS-CoV-2 pneumonia in non-critically ill hospitalized patients secondarily presenting with clinical deterioration and increase in oxygen requirement without any identified worsening factors. METHODS: We consecutively enrolled patients without clinical or biological evidence for superinfection, without left ventricular dysfunction and for whom a pulmonary embolism was discarded by computed tomography (CT) pulmonary angiography. We investigated lung ventilation and perfusion (LVP) by LVP scintigraphy, and, 24 h later, left and right ventricular function by Tc-99m-labeled albumin-gated blood-pool scintigraphy with late (60 mn) tomographic albumin images on the lungs to evaluate lung albumin retention that could indicate microvascular injuries with secondary edema. RESULTS: We included 20 patients with confirmed SARS-CoV-2 pneumonia. All had CT evidence of organizing pneumonia and normal left ventricular ejection fraction. No patient demonstrated preserved ventilation with perfusion defect (mismatch), which may discard a distal lung thrombosis. Patterns of ventilation and perfusion were heterogeneous in seven patients (35%) with healthy lung segments presenting a relative paradoxical hypoperfusion and hypoventilation compared with segments with organizing pneumonia presenting a relative enhancement in perfusion and preserved ventilation. Lung albumin retention in area of organizing pneumonia was observed in 12 patients (60%), indicating microvascular injuries, increase in vessel permeability, and secondary edema. CONCLUSION: In hospitalized non-critically ill patients without evidence of superinfection, pulmonary embolism, or cardiac dysfunction, various types of damage may contribute to clinical deterioration including microvascular injuries and secondary edema, inconsistencies in lung segments vascularization suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others. SUMMARY STATEMENT: Microvascular injuries and dysregulation of the balance in perfusion between segments affected by COVID-19 and others are present in non-critically ill patients without other known aggravating factors. KEY RESULTS: In non-critically ill patients without evidence of superinfection, pulmonary embolism, macroscopic distal thrombosis or cardiac dysfunction, various types of damage may contribute to clinical deterioration including 1/ microvascular injuries and secondary edema, 2/ inconsistencies in lung segments vascularization with hypervascularization of consolidated segments contrasting with hypoperfusion of not affected segments, suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others.

Trial Sequential Analysis and Updated Meta-Analysis of Fluvoxamine on Clinical Deterioration in Adult Patients with Symptomatic COVID-19 Infection.

Preliminary meta-analyses suggested that fluvoxamine was effective in treating COVID-19 infection. However, the reliability of this evidence has not yet been examined. MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify any randomized controlled trials (RCTs) from the inception of the databases to 5 February 2023. We used trial sequential analysis (TSA) to examine the reliability of the current existing evidence on the benefits of fluvoxamine on COVID-19 infection. The primary outcome was clinical deterioration, as defined in the original study (reported as odds ratio (OR), with 95% confidence intervals), and the secondary outcome was hospitalization. In the TSA, we used the relative risk reduction thresholds of 10, 20, and 30%. The updated meta-analysis of the five RCTs showed that fluvoxamine was not associated with lower odds of clinical deterioration when compared with a placebo (OR: 0.81; 0.59-1.11). The effect of fluvoxamine lay within the futility boundary (i.e., lack of effect) when using a 30% relative risk reduction threshold. The effect estimates lay between the superiority and futility boundary using the 10% and 20% threshold, and the required size of information was not reached for these two thresholds. The effect of fluvoxamine on the odds of hospitalization was not statistically significant (0.76; 0.56-1.03). In conclusion, there is no reliable evidence that fluvoxamine, when compared to a placebo, reduces the relative risk of clinical deterioration among adult patients with COVID-19 infection by 30%, and a relative risk reduction of 20% or 10% is still uncertain. The role of fluvoxamine as a COVID-19 treatment cannot be justified.

Rapid systematic review of respiratory rate as a vital sign of clinical deterioration in COVID-19.

OBJECTIVES: This meta-analysis aimed to establish a clinical evidence base for respiratory rate (RR) as a single predictor of early-onset COVID-19. The review also looked to determine the practical implementation of mobile respiratory rate measuring devices where information was available. METHODS: We focused on domestic settings with older adults. Relevant studies were identified through MEDLINE, Embase, and CENTRAL databases. A snowballing method was also used. Articles published from the beginning of the COVID-19 pandemic (2019) until Feb 2022 were selected. Databases were searched for terms related to COVID-19 and respiratory rate measurements in domestic patients. RESULTS: A total of 2,889 articles were screened for relevant content, of which 60 full-text publications were included. We compared the Odds Ratios and statistically significant results of both vital signs. CONCLUSION: Multinational studies across dozens of countries have shown respiratory rate to have predictive accuracy in detecting COVID-19 deterioration. However, considerable variability is present in the data, making it harder to be sure about the effects. There is no meaningful difference in data quality in terms of variability (95% CI intervals) between vital signs as predictors of decline in COVID-19 patients. Contextual and economic factors will likely determine the choice of measurement used.

Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline.

This rapid practice guideline provides evidence-based recommendations for the use of awake proning in adult patients with acute hypoxemic respiratory failure due to COVID-19. The panel included 20 experts from 12 countries, including one patient representative, and used a strict conflict of interest policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the guidelines in intensive care, development, and evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation (GRADE) method we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework. We conducted an electronic vote, requiring >80% agreement amongst the panel for a recommendation to be adopted. The panel made a strong recommendation for a trial of awake proning in adult patients with COVID-19 related hypoxemic acute respiratory failure who are not invasively ventilated. Awake proning appears to reduce the risk of tracheal intubation, although it may not reduce mortality. The panel judged that most patients would want a trial of awake proning, although this may not be feasible in some patients and some patients may not tolerate it. However, given the high risk of clinical deterioration amongst these patients, awake proning should be conducted in an area where patients can be monitored by staff experienced in rapidly detecting and managing clinical deterioration. This RPG panel recommends a trial of awake prone positioning in patients with acute hypoxemic respiratory failure due to COVID-19.

Systematic review with meta-analysis of mid-regional pro-adrenomedullin (MR-proadm) as a prognostic marker in Covid-19-hospitalized patients.

BACKGROUND: Mid-regional pro-adrenomedullin (MR-proADM) is useful for risk stratification in patients with sepsis and respiratory infections. The study's purpose was to assess the available data and determine the association between MR-proADM levels and mortality in COVID-19 participants. METHODS: A comprehensive literature search of medical electronic databases was performed including PubMed, Web of Science, Scopus, Cochrane, and grey literature for relevant data published from 1 January 2020, to 20 November 2022. Mean differences (MD) with 95% confidence intervals (CI) were calculated. RESULTS: Fourteen studies reported MR-proADM levels in survivors vs. non-survivors of COVID-19 patients. Pooled analysis showed that MR-proADM level in the survivor group was 0.841 ± 0.295 nmol/L for patients who survive COVID-19, compared to 1.692 ± 0.761 nmol/L for non-survivors (MD = -0.78; 95%CI: -0.92 to -0.64; p < 0.001). CONCLUSIONS: The main finding of this study is that mortality of COVID-19 is linked to MR-proADM levels, according to this meta-analysis. The use of MR-proADM might be extremely beneficial in triaging, assessing probable therapy escalation, predicting potential complications during therapy or significant clinical deterioration of patients, and avoiding admission which may not be necessary. Nevertheless, in order to confirm the obtained data, it is necessary to conduct large prospective studies that will address the potential diagnostic role of MR-proADM as a marker of COVID-19 severity.KEY MESSAGESSeverity of COVID-19 seems to be linked to MR-proADM levels and can be used as a potential marker for predicting a patient's clinical course.The use of MR-proADM might be beneficial in triaging, assessing probable therapy escalation, predicting potential complications during therapy or significant clinical deterioration of patients, and avoiding admission which may not be necessary.For patients with COVID-19, MR-proADM may be an excellent prognostic indicator because it is a marker of endothelial function that may predict the precise impact on the equilibrium between vascular relaxation and contraction and lowers platelet aggregation inhibitors, coagulation inhibitors, and fibrinolysis activators in favor of clotting factors.

Evaluation of the utility of NEWS2 during the COVID-19 pandemic.

The emergence of the COVID-19 pandemic resulted in a dramatic increase in acutely ill patients presenting to hospitals with life-threatening acute respiratory disease. There was an immediate need for effective triage systems to facilitate clinical decision making. This review assesses the performance of the National Early Warning Score 2 (NEWS2) in two contexts. Firstly, the ability to detect acute illness severity and likely clinical deterioration in patients presenting to hospitals with COVID-19. Secondly, the use of NEWS2 in the longitudinal monitoring to detect acute clinical deterioration in hospitalised patients with COVID-19. NEWS2 appeared to be at least comparable and, often, superior to other scoring systems (such as qSOFA and CURB-65), and provided an earlier alert of deterioration. A NEWS2 of 5 had high short-term sensitivity within and was unlikely to miss patients with COVID-19 who go on to deteriorate, but this comes with moderate specificity. However, the specificity of these systems is likely underestimated because preventing deterioration is their purpose.NEWS2 is an adjunct to clinical decision making and has served that purpose during the COVID-19 pandemic, playing an important role in communicating illness severity, clinical deterioration, triaging patients to appropriate levels of care and prompting completion of treatment escalation plans for those with high scores and at imminent risk of deterioration.

Reducing COVID-19 Health Inequities by Identifying Social Needs and Clinical Deterioration of Discharged Emergency Department Patients.

INTRODUCTION: The decision to discharge a patient from the hospital with confirmed or suspected coronavirus 2019 (COVID-19) is fraught with challenges. Patients who are discharged home must be both medically stable and able to safely isolate to prevent disease spread. Socioeconomically disadvantaged patient populations in particular may lack resources to safely quarantine and are at high risk for COVID-19 morbidity. METHODS: We developed a telehealth follow-up program for emergency department (ED) patients who received testing for COVID-19 from April 24-June 29, 2020 and were discharged home. Patients who were discharged with a pending COVID-19 test received follow-up calls on Days 1, 4, and 8. The objective of our program was to screen and provide referrals for health-related social needs (HRSN), conduct clinical screening for worsening symptoms, and deliver risk-reduction strategies for vulnerable individuals. We conducted retrospective chart reviews on all patients in this cohort to collect demographic information, testing results, and outcomes of clinical symptom and HRSN screening. Our primary outcome measurement was the need for clinical reassessment and referral for an unmet HRSN. RESULTS: From April 24-June 29, 2020, we made calls to 1,468 patients tested for COVID-19 and discharged home. On Day 4, we reached 67.0% of the 1,468 patients called. Of these, 15.9% were referred to a physician's assistant (PA) out of concern for clinical worsening and 12.4% were referred to an emergency department (ED) patient navigator for HRSNs. On Day 8, we reached 81.8% of the 122 patients called. Of these, 19.7% were referred to a PA for clinical reassessment and 14.0% were referred to an ED patient navigator for HRSNs. Our intervention reached 1,069 patients, of whom 12.6% required referral for HRSNs and 1.3% (n = 14) were referred to the ED or Respiratory Illness Clinic due to concern for worsening clinical symptoms. CONCLUSION: In this patient population, the demand for interventions to address social needs was as high as the need for clinical reassessment. Similar ED-based programs should be considered to help support patients' interdependent social and health needs beyond those related to COVID-19.

Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, placebo-controlled trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may cause severe life-threatening diseases called acute respiratory distress syndrome (ARDS) owing to cytokine storms. The mortality rate of COVID-19-related ARDS is as high as 40% to 50%. However, effective treatment for the extensive release of acute inflammatory mediators induced by hyperactive and inappropriate immune responses is very limited. Many anti-inflammatory drugs with variable efficacies have been investigated. Colchicine inhibits interleukin 1 beta (IL-1ß) and its subsequent inflammatory cascade by primarily blocking pyrin and nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) activation. Therefore, this cheap, widely available, oral drug might provide an added benefit in combating the cytokine storm in COVID-19. Here, we sought to determine whether adding colchicine to other standards of care could be beneficial for moderate COVID-19 pneumonia in terms of the requirement for advanced respiratory support and mortality. METHODS AND FINDINGS: This blinded placebo-controlled drug trial was conducted at the Dhaka Medical College Hospital, Dhaka, Bangladesh. A total of 300 patients with moderate COVID-19 based on a positive RT-PCR result were enrolled based on strict selection criteria from June 2020 to November 2020. Patients were randomly assigned to either treatment group in a 1:1 ratio. Patients were administered 1.2 mg of colchicine on day 1 followed by daily treatment with 0.6 mg of colchicine for 13 days or placebo along with the standard of care. The primary outcome was the time to clinical deterioration from randomization to two or more points on a seven-category ordinal scale within the 14 days post-randomization. Clinical outcomes were also recorded on day 28. The primary endpoint was met by 9 (6.2%) patients in the placebo group and 4 (2.7%) patients in the colchicine group (P = 0.171), which corresponds to a hazard ratio (95% CI) of 0.44 (0.13-1.43). Additional analysis of the outcomes on day 28 revealed significantly lower clinical deterioration (defined as a decrease by two or more points) in the colchicine group, with a hazard ratio [95%CI] of 0.29 [0.098-0.917], (P = 0.035). Despite a 56% reduction in the need for mechanical ventilation and death with colchicine treatment on day 14, the reduction was not statistically significant. On day 28, colchicine significantly reduced clinical deterioration measured as the need for mechanical ventilation and all-cause mortality. CONCLUSION: Colchicine was not found to have a significant beneficial effect on reducing mortality and the need for mechanical ventilation. However, a delayed beneficial effect was observed. Therefore, further studies should be conducted to evaluate the late benefits of colchicine. CLINICAL TRIAL REGISTRATION: Clinical trial registration no: ClinicalTrials.gov Identifier: NCT04527562 https://www.google.com/search?client=firefox-b-d&q=NCT04527562.

Prediction of low pulse oxygen saturation in COVID-19 using remote monitoring post hospital discharge.

BACKGROUND: Monitoring systems have been developed during the COVID-19 pandemic enabling clinicians to remotely monitor physiological measures including pulse oxygen saturation (SpO2), heart rate (HR), and breathlessness in patients after discharge from hospital. These data may be leveraged to understand how symptoms vary over time in COVID-19 patients. There is also potential to use remote monitoring systems to predict clinical deterioration allowing early identification of patients in need of intervention. METHODS: A remote monitoring system was used to monitor 209 patients diagnosed with COVID-19 in the period following hospital discharge. This system consisted of a patient-facing app paired with a Bluetooth-enabled pulse oximeter (measuring SpO2 and HR) linked to a secure portal where data were available for clinical review. Breathlessness score was entered manually to the app. Clinical teams were alerted automatically when SpO2 < 94 %. In this study, data recorded during the initial ten days of monitoring were retrospectively examined, and a random forest model was developed to predict SpO2 < 94 % on a given day using SpO2 and HR data from the two previous days and day of discharge. RESULTS: Over the 10-day monitoring period, mean SpO2 and HR increased significantly, while breathlessness decreased. The coefficient of variation in SpO2, HR and breathlessness also decreased over the monitoring period. The model predicted SpO2 alerts (SpO2 < 94 %) with a mean cross-validated. sensitivity of 66 ± 18.57 %, specificity of 88.31 ± 10.97 % and area under the receiver operating characteristic of 0.80 ± 0.11. Patient age and sex were not significantly associated with the occurrence of asymptomatic SpO2 alerts. CONCLUSION: Results indicate that SpO2 alerts (SpO2 < 94 %) on a given day can be predicted using SpO2 and heart rate data captured on the two preceding days via remote monitoring. The methods presented may help early identification of patients with COVID-19 at risk of clinical deterioration using remote monitoring.

Fluvoxamine for the treatment of COVID-19.

BACKGROUND: Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that has been approved for the treatment of depression, obsessive-compulsive disorder, and a variety of anxiety disorders; it is available as an oral preparation. Fluvoxamine has not been approved for the treatment of infections, but has been used in the early treatment of people with mild to moderate COVID-19. As there are only a few effective therapies for people with COVID-19 in the community, a thorough understanding of the current evidence regarding the efficacy and safety of fluvoxamine as an anti-inflammatory and possible anti-viral treatment for COVID-19, based on randomised controlled trials (RCTs), is needed. OBJECTIVES: To assess the efficacy and safety of fluvoxamine in addition to standard care, compared to standard care (alone or with placebo), or any other active pharmacological comparator with proven efficacy for the treatment of COVID-19 outpatients and inpatients. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (including Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ClinicalTrials.gov, WHO ICTRP, medRxiv), Web of Science and WHO COVID-19 Global literature on COVID-19 to identify completed and ongoing studies up to 1 February 2022. SELECTION CRITERIA: We included RCTs that compared fluvoxamine in addition to standard care (also including no intervention), with standard care (alone or with placebo), or any other active pharmacological comparator with proven efficacy in clinical trials for the treatment of people with confirmed COVID-19, irrespective of disease severity, in both inpatients and outpatients. Co-interventions needed to be the same in both study arms. We excluded studies comparing fluvoxamine to other pharmacological interventions with unproven efficacy. DATA COLLECTION AND ANALYSIS: We assessed risk of bias of primary outcomes using the Cochrane Risk of Bias 2 tool for RCTs. We used GRADE to rate the certainty of evidence to treat people with asymptomatic to severe COVID-19 for the primary outcomes including mortality, clinical deterioration, clinical improvement, quality of life, serious adverse events, adverse events of any grade, and suicide or suicide attempt. MAIN RESULTS: We identified two completed studies with a total of 1649 symptomatic participants. One study was conducted in the USA (study with 152 participants, 80 and 72 participants per study arm) and the other study in Brazil (study with 1497 high-risk participants for progression to severe disease, 741 and 756 participants per study arm) among outpatients with mild COVID-19. Both studies were double-blind, placebo-controlled trials in which participants were prescribed 100 mg fluvoxamine two or three times daily for a maximum of 15 days. We identified five ongoing studies and two studies awaiting classification (due to translation issues, and due to missing published data). We found no published studies comparing fluvoxamine to other pharmacological interventions of proven efficacy. We assessed both included studies to have an overall high risk of bias. Fluvoxamine for the treatment of COVID-19 in inpatients We did not identify any completed studies of inpatients. Fluvoxamine for the treatment of COVID-19 in outpatients Fluvoxamine in addition to standard care may slightly reduce all-cause mortality at day 28 (RR 0.69, 95% CI 0.38 to 1.27; risk difference (RD) 9 per 1000; 2 studies, 1649 participants; low-certainty evidence), and may reduce clinical deterioration defined as all-cause hospital admission or death before hospital admission (RR 0.55, 95% CI 0.16 to 1.89; RD 57 per 1000; 2 studies, 1649 participants; low-certainty evidence). We are very uncertain regarding the effect of fluvoxamine on serious adverse events (RR 0.56, 95% CI 0.15 to 2.03; RD 54 per 1000; 2 studies, 1649 participants; very low-certainty evidence) or adverse events of any grade (RR 1.06, 95% CI 0.82 to 1.37; RD 7 per 1000; 2 studies, 1649 participants; very low-certainty evidence). Neither of the studies reported on symptom resolution (clinical improvement), quality of life or suicide/suicide attempt. AUTHORS' CONCLUSIONS: Based on a low-certainty evidence, fluvoxamine may slightly reduce all-cause mortality at day 28, and may reduce the risk of admission to hospital or death in outpatients with mild COVID-19. However, we are very uncertain regarding the effect of fluvoxamine on serious adverse events, or any adverse events. In accordance with the living approach of this review, we will continually update our search and include eligible trials as they arise, to complete any gaps in the evidence.

Early predictors of clinical deterioration in a cohort of outpatients with COVID-19 in southern Italy: A multicenter observational study.

Data regarding early predictors of clinical deterioration in patients with infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still scarce. The aim of the study is to identify early symptoms or signs that may be associated with severe coronavirus disease 2019 (COVID-19). We conducted a multicentre prospective cohort study on a cohort of patients with COVID-19 in home isolation from March 2020 to April 2021. We assessed longitudinal clinical data (fever, dyspnea, need for hospitalization) through video calls at three specific time points: the beginning of symptoms or the day of the first positivity of the nasopharyngeal swab for SARS-CoV-2-RNA (t0 ), and 3 (t3 ) and 7 (t7 ) days after the onset of symptoms. We included 329 patients with COVID-19: 182 (55.3%) males, mean age 53.4 ± 17.4 years, median Charlson comorbidity index (CCI) of 1 (0-3). Of the 329 patients enrolled, 171 (51.98%) had a mild, 81 (24.6%) a moderate, and 77 (23.4%) a severe illness; 151 (45.9%) were hospitalized. Compared to patients with mild COVID-19, moderate and severe patients were older (p < 0.001) and had more comorbidities, especially hypertension (p < 0.001) and cardiovascular diseases (p = 0.01). At t3 and t7 , we found a significant higher rate of persisting fever (≥37°C) among patients with moderate (91.4% and 58.0% at t3 and t7 , respectively; p < 0.001) and severe outcome (75.3% and 63.6%, respectively; p < 0.001) compared to mild COVID-19 outcome (27.5% and 11.7%, respectively; p < 0.001). Factors independently associated with a more severe outcome were persisting fever at t3 and t7 , increasing age, and CCI above 2 points. Persisting fever at t3 and t7 seems to be related to a more severe COVID-19. This data may be useful to assess hospitalization criteria and optimize the use of resources in the outpatient setting.

Outcome of mild SARS-CoV-2-infected renal transplant recipients managed by supervised home-based self-monitoring.

OBJECTIVES: We aimed to compare the outcomes of COVID-19 Renal Transplant Recipients (RTRs) managed on an ambulatory basis to that of inpatient management. DESIGN, SETTING, MATERIALS, AND METHODS: We performed a retrospective study in Lucknow, India, comparing the ambulatory management with the historical cohort managed in the hospital.R RTRs with mild COVID-19 were managed by supervised home-based self-monitoring (HBSM), a strategy to manage this high-risk group on an outpatient basis during the second wave of the pandemic. The primary outcome was the clinical deterioration to a higher severity category among RTRs with mild COVID-19 managed by HBSM compared to hospitalized patients within two weeks of disease onset. RESULTS: Of the 149 RTRs with mild COVID-19, 94 (63%) and 55 (37%) were managed by HBSM and in the hospital, respectively. The proportion of RTRs who clinically deteriorated to a higher severity category (moderate or severe category) was similar among both groups (28.7% versus 27.2%, P=0.849). Among RTRs with clinical deterioration, COVID-19-related death was reported in two patients of the HBSM group and in none of the patients of the hospitalized group. Graft dysfunction was higher in the hospitalized group (7.4% versus 27.2%, P=0.002). Median time to complete clinical recovery (7 days in both groups), secondary bacterial infections (25% versus 33.3%, P=0.41), and the mean decline in EQ-5D score from baseline at six weeks (-6.6 versus-4.3, P=0.105) were found to be similar in both groups.

Statin and aspirin as adjuvant therapy in hospitalised patients with SARS-CoV-2 infection: a randomised clinical trial (RESIST trial).

BACKGROUND: Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial. METHODS: In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. RESULTS: The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41-2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27-1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. CONCLUSIONS: Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration. Trial Registry Number CTRI/2020/07/026791 ( http://ctri.nic.in ; registered on 25/07/2020).

Machine learning-based model for prediction of clinical deterioration in hospitalized patients by COVID 19.

Despite the publication of great number of tools to aid decisions in COVID-19 patients, there is a lack of good instruments to predict clinical deterioration. COVID19-Osakidetza is a prospective cohort study recruiting COVID-19 patients. We collected information from baseline to discharge on: sociodemographic characteristics, comorbidities and associated medications, vital signs, treatment received and lab test results. Outcome was need for intensive ventilatory support (with at least standard high-flow oxygen face mask with a reservoir bag for at least 6 h and need for more intensive therapy afterwards or Optiflow high-flow nasal cannula or noninvasive or invasive mechanical ventilation) and/or admission to a critical care unit and/or death during hospitalization. We developed a Catboost model summarizing the findings using Shapley Additive Explanations. Performance of the model was assessed using area under the receiver operating characteristic and prediction recall curves (AUROC and AUPRC respectively) and calibrated using the Hosmer-Lemeshow test. Overall, 1568 patients were included in the derivation cohort and 956 in the (external) validation cohort. The percentages of patients who reached the composite endpoint were 23.3% vs 20% respectively. The strongest predictors of clinical deterioration were arterial blood oxygen pressure, followed by age, levels of several markers of inflammation (procalcitonin, LDH, CRP) and alterations in blood count and coagulation. Some medications, namely, ATC AO2 (antiacids) and N05 (neuroleptics) were also among the group of main predictors, together with C03 (diuretics). In the validation set, the CatBoost AUROC was 0.79, AUPRC 0.21 and Hosmer-Lemeshow test statistic 0.36. We present a machine learning-based prediction model with excellent performance properties to implement in EHRs. Our main goal was to predict progression to a score of 5 or higher on the WHO Clinical Progression Scale before patients required mechanical ventilation. Future steps are to externally validate the model in other settings and in a cohort from a different period and to apply the algorithm in clinical practice.Registration: ClinicalTrials.gov Identifier: NCT04463706.

Artificial intelligence and clinical deterioration.

PURPOSE OF REVIEW: To provide an overview of the systems being used to identify and predict clinical deterioration in hospitalised patients, with focus on the current and future role of artificial intelligence (AI). RECENT FINDINGS: There are five leading AI driven systems in this field: the Advanced Alert Monitor (AAM), the electronic Cardiac Arrest Risk Triage (eCART) score, Hospital wide Alert Via Electronic Noticeboard, the Mayo Clinic Early Warning Score, and the Rothman Index (RI). Each uses Electronic Patient Record (EPR) data and machine learning to predict adverse events. Less mature but relevant evolutions are occurring in the fields of Natural Language Processing, Time and Motion Studies, AI Sepsis and COVID-19 algorithms. SUMMARY: Research-based AI-driven systems to predict clinical deterioration are increasingly being developed, but few are being implemented into clinical workflows. Escobar et al. (AAM) provide the current gold standard for robust model development and implementation methodology. Multiple technologies show promise, however, the pathway to meaningfully affect patient outcomes remains challenging.

Cardiovascular vulnerability predicts hospitalisation in primary care clinically suspected and confirmed COVID-19 patients: A model development and validation study.

OBJECTIVES: Cardiovascular conditions were shown to be predictive of clinical deterioration in hospitalised patients with coronavirus disease 2019 (COVID-19). Whether this also holds for outpatients managed in primary care is yet unknown. The aim of this study was to determine the incremental value of cardiovascular vulnerability in predicting the risk of hospital referral in primary care COVID-19 outpatients. DESIGN: Analysis of anonymised routine care data extracted from electronic medical records from three large Dutch primary care registries. SETTING: Primary care. PARTICIPANTS: Consecutive adult patients seen in primary care for COVID-19 symptoms in the 'first wave' of COVID-19 infections (March 1 2020 to June 1 2020) and in the 'second wave' (June 1 2020 to April 15 2021) in the Netherlands. OUTCOME MEASURES: A multivariable logistic regression model was fitted to predict hospital referral within 90 days after first COVID-19 consultation in primary care. Data from the 'first wave' was used for derivation (n = 5,475 patients). Age, sex, the interaction between age and sex, and the number of cardiovascular conditions and/or diabetes (0, 1, or ≥2) were pre-specified as candidate predictors. This full model was (i) compared to a simple model including only age and sex and its interaction, and (ii) externally validated in COVID-19 patients during the 'second wave' (n = 16,693). RESULTS: The full model performed better than the simple model (likelihood ratio test p<0.001). Older male patients with multiple cardiovascular conditions and/or diabetes had the highest predicted risk of hospital referral, reaching risks above 15-20%, whereas on average this risk was 5.1%. The temporally validated c-statistic was 0.747 (95%CI 0.729-0.764) and the model showed good calibration upon validation. CONCLUSIONS: For patients with COVID-19 symptoms managed in primary care, the risk of hospital referral was on average 5.1%. Older, male and cardiovascular vulnerable COVID-19 patients are more at risk for hospital referral.