Prone positioning of patients with moderate hypoxia due to COVID-19: A multicenter pragmatic randomized trial

ObjectivesTo assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients hospitalized with COVID-19 DesignPragmatic randomized clinical trial of prone positioning of patients hospitalized with COVID-19 across 15 hospitals in Canada and the United States from May 2020 until May 2021. SettingsPatients were eligible is they had a laboratory-confirmed or a clinically highly suspected diagnosis of COVID-19, required supplemental oxygen (up to 50% fraction of inspired oxygen [FiO2]), and were able to independently prone with verbal instruction. (NCT04383613). Main Outcome MeasuresThe primary outcome was a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as requiring at least 60% FiO2 for at least 24 hours. Secondary outcomes included the change in the ratio of oxygen saturation to FiO2 (S/F ratio). ResultsA total of 248 patients were included. The trial was stopped early on the basis of futility for the pre-specified primary outcome. The median time from hospital admission until randomization was 1 day, the median age of patients was 56 years (interquartile range [IQR] 45,65), 36% were female, and 90% of patients were receiving oxygen via nasal prongs at the time of randomization. The median time spent prone in the first 72 hours was 6 hours total (IQR 1.5,12.8) for the prone arm compared to 0 hours (0,2) in the control arm. The risk of the primary outcome was similar between the prone group (18 [14.3%] events) and the standard care group (17 [13.9%] events), odds ratio 0.92 (95% CI 0.44 to 1.92). The change in the S/F ratio after 72 hours was similar for patients randomized to prone compared to standard of care. ConclusionAmong hypoxic but not critically patients with COVID-19 in hospital, a multifaceted intervention to increase prone positioning did not improve outcomes. Adherence to prone positioning was poor, despite multiple efforts. Subsequent trials of prone positioning should aim to develop strategies to improve adherence to awake prone positioning. What is already known on this topicProne positioning is considered standard of care for mechanically ventilated patients who have severe acute respiratory distress syndrome. Recent data suggest prone positioning is beneficial for patients with COVID-19 who are requiring high flow oxygen. It is unknown of prone positioning is beneficial for patients not on high flow oxygen. What this study addsProne positioning is generally not well tolerated and innovative approaches are needed to improve adherence. Clinical and physiologic outcomes were not improved with prone positioning among hypoxic but not critically ill patients hospitalized with COVID-19.

Heparin for Moderately Ill Patients with Covid-19

BackgroundHeparin, in addition to its anticoagulant properties, has anti-inflammatory and potential anti-viral effects, and may improve endothelial function in patients with Covid-19. Early initiation of therapeutic heparin could decrease the thrombo-inflammatory process, and reduce the risk of critical illness or death. MethodsWe randomly assigned moderately ill hospitalized ward patients admitted for Covid-19 with elevated D-dimer level to therapeutic or prophylactic heparin. The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation or ICU admission. Safety outcomes included major bleeding. Analysis was by intention-to-treat. ResultsAt 28 days, the primary composite outcome occurred in 37 of 228 patients (16.2%) assigned to therapeutic heparin, and 52 of 237 patients (21.9%) assigned to prophylactic heparin (odds ratio, 0.69; 95% confidence interval [CI], 0.43 to 1.10; p=0.12). Four patients (1.8%) assigned to therapeutic heparin died compared with 18 patients (7.6%) assigned to prophylactic heparin (odds ratio, 0.22; 95%-CI, 0.07 to 0.65). The composite of all-cause mortality or any mechanical ventilation occurred in 23 (10.1%) in the therapeutic heparin group and 38 (16.0%) in the prophylactic heparin group (odds ratio, 0.59; 95%-CI, 0.34 to 1.02). Major bleeding occurred in 2 patients (0.9%) with therapeutic heparin and 4 patients (1.7%) with prophylactic heparin (odds ratio, 0.52; 95%-CI, 0.09 to 2.85). ConclusionsIn moderately ill ward patients with Covid-19 and elevated D-dimer level, therapeutic heparin did not significantly reduce the primary outcome but decreased the odds of death at 28 days. Trial registration numbers: NCT04362085; NCT04444700

Assessing the utility of lymphocyte count to diagnose COVID-19

BackgroundCOronaVirus Disease 2019 (COVID-19) can be challenging to diagnose, because symptoms are non-specific, clinical presentations are heterogeneous, and false negative tests can occur. Our objective was to assess the utility of lymphocyte count to differentiate COVID-19 from influenza or community-acquired pneumonia (CAP). MethodsWe conducted a cohort study of adults hospitalized with COVID-19 or another respiratory infection (i.e., influenza, CAP) at seven hospitals in Ontario, Canada.The first available lymphocyte count during the hospitalization was used. Standard test characteristics for lymphocyte count (x109/L) were calculated (i.e., sensitivity, specificity, area under the receiver operating curve [AUC]). All analyses were conducting using R. ResultsThere were 869 hospitalizations for COVID-19, 669 for influenza, and 3009 for CAP. The mean age across the three groups was 67 and patients with pneumonia were older than those with influenza or COVID19, and approximately 46% were woman. The median lymphocyte count was nearly identical for the three groups of patients: 1.0 x109/L (interquartile range [IQR]:0.7,2.0) for COVID-19, 0.9 x109/L (IQR 0.6,1.0) for influenza, and 1.0 x109/L (IQR 0.6,2.0) for CAP. At a lymphocyte threshold of less than 2.0 x109/L, the sensitivity was 87% and the specificity was approximately 10%. As the lymphocyte threshold increased, the sensitivity of diagnosing COVID-19 increased while the specificity decreased. The AUC for lymphocyte count was approximately 50%. InterpretationLymphocyte count has poor diagnostic discrimination to differentiate between COVID-19 and other respiratory illnesses. The lymphopenia we consistently observed across the three illnesses in our study may reflect a non-specific sign of illness severity. However, lymphocyte count above 2.0 x109/L may be useful in ruling out COVID-19 (sensitivity = 87%).

Patient characteristics, clinical care, resource use, and outcomes associated with hospitalization for COVID-19 in the Toronto area

BackgroundPatient characteristics, clinical care, resource use, and outcomes associated with hospitalization for coronavirus disease (COVID-19) in Canada are not well described. MethodsWe described all adult discharges from inpatient medical services and medical-surgical intensive care units (ICU) between November 1, 2019 and June 30, 2020 at 7 hospitals in Toronto and Mississauga, Ontario. We compared patients hospitalized with COVID-19, influenza and all other conditions using multivariable regression models controlling for patient age, sex, comorbidity, and residence in long-term-care. ResultsThere were 43,462 discharges in the study period, including 1,027 (3.0%) with COVID-19 and 783 (2.3%) with influenza. Patients with COVID-19 had similar age to patients with influenza and other conditions (median age 65 years vs. 68 years and 68 years, respectively, SD<0.1). Patients with COVID-19 were more likely to be male (59.1%) and 11.7% were long-term care residents. Patients younger than 50 years accounted for 21.2% of all admissions for COVID-19 and 24.0% of ICU admissions. Compared to influenza, patients with COVID-19 had significantly greater mortality (unadjusted 19.9% vs 6.1%, aRR: 3.47, 95%CI: 2.57, 4.67), ICU use (unadjusted 26.4% vs 18.0%, aRR 1.52, 95%CI: 1.27, 1.83) and hospital length-of-stay (unadjusted median 8.7 days vs 4.8 days, aRR: 1.40, 95%CI: 1.20, 1.64), and not significantly different 30-day readmission (unadjusted 8.6% vs 8.2%, aRR: 1.01, 95%CI: 0.72, 1.42). InterpretationAdults hospitalized with COVID-19 during the first wave of the pandemic used substantial hospital resources and suffered high mortality. COVID-19 was associated with significantly greater mortality, ICU use, and hospital length-of-stay than influenza.

Adjunctive Corticosteroids for COVID-19: A Retrospective Cohort Study

BackgroundCoronavirus disease 2019 (COVID-19) is associated with severe pneumonia, respiratory failure and death. We aim to evaluate the efficacy of adjunctive corticosteroids in the management of COVID-19. MethodsThis is a retrospective cohort study of hospitalized adults ([≥]18 years) who were diagnosed with COVID-19 and were given treatment. Treatment included hydroxycholoroquine and lopinavir-ritonavir. Corticosteroids were included as adjunctive therapy in mid-April, 2020. We compared composite outcomes of clinical progression and invasive mechanical ventilation (MV) or death between group that received treatment only (Group A) versus group that received adjunctive corticosteroids (Group B). Entropy balancing was used to generate stabilized weight for covariates between treatment groups. Unweighted Kaplan-Meir curves, weighted and adjusted Cox regression analysis were used to estimate effect of adjunctive corticosteroids on composite outcomes. Subgroup analysis was performed on those with pneumonia. ResultsOf 1046 patients with COVID-19, 57 received treatment alone (Group A) and 35 received adjunctive corticosteroids in addition to treatment (Group B). Median day of illness at treatment initiation was 5 day. There were 44 patients with pneumonia; 68.9% of them were not requiring supplemental oxygen at treatment initiation. Overall, 17 (18.5%) of 92 patients had clinical progression including 13 (22.8%) of 57 patients in Group A versus 4 (11.4%) of 35 patients in Group B (p=0.172). Unweighted Kaplan-Meier estimates showed no significant difference in the proportion of patients who had clinical progression or invasive MV or death between the 2 treatment groups. However in those with pneumonia, there were lower proportions of patients in Group B with clinical progression (11.1%, 95% CI 0.0 - 22.2 versus 58.8%, 95% CI 27.3 - 76.7, log rank p<0.001); and invasive MV or death (11.3%, 95% CI 0.0 - 22.5 versus 41.2%, 95% CI 12.4. - 60.5, log rank p=0.016). In weighted and adjusted cox regression analysis, patients in Group B were less likely to have clinical progression, (adjusted HR [aHR] 0.08, 95% CI 0.01-0.99, p=0.049) but there was no statistical significant difference in risk of requiring invasive MV or death (aHR 0.22, 95%CI 0.02 - 2.54, p=0.22). In subgroup with pneumonia, patients in Group B were significantly at lower risk of clinical progression (aHR 0.15, 95% CI 0.06 - 0.39, p<0.001) and requiring invasive MV compared to Group A (aHR 0.30, 0.10-0.87, p=0.029). ConclusionsUse of adjunctive corticosteroids is associated with lower risk of clinical progression and invasive MV or death, especially in those with pneumonia. Concurrent use of antivirals and corticosteroids should be considered in the management of COVID-19 related pneumonia.

Factors associated with prolonged length of stay in older patients

<p><b>INTRODUCTION</b>Prolonged stay in acute hospitals increases the risk of hospital-acquired infections in older patients, and disrupts patient flow and access to care due to bed shortages. We aimed to investigate the factors associated with prolonged length of stay (pLOS) among older patients (aged ≥ 78 years) in a tertiary hospital, to identify the potentially modifiable risk factors that could direct interventions to reduce length of stay (LOS).</p><p><b>METHODS</b>During a three-month period from January 2013 to March 2013, we identified 72 patients with pLOS (LOS ≥ 21 days) and compared their demographic and clinical variables with that of 281 randomly selected control patients (LOS < 21 days) using univariate and multivariate logistic regression analyses.</p><p><b>RESULTS</b>The mean age of the patients was 85.30 ± 5.34 years; 54% of them were female and 72% were of Chinese ethnicity. Logistic regression revealed the following significant factors for increased LOS: discharge to intermediate and long-term care services (odds ratio [OR] 9.22, 95% confidence interval [CI] 3.56-23.89; p < 0.001); increased severity of illness (OR 2.41, 95% CI 1.12-5.21; p = 0.025); and presence of caregiver stress (OR 3.85, 95% CI 1.67-8.91; p = 0.002).</p><p><b>CONCLUSION</b>Presence of caregiver stress and nursing home placement are potential modifiable risk factors of pLOS among older patients. Early identification and management of caregiver stress, as well as expediting discharge planning, may help to reduce the length of stay for this cohort.</p>

Continence

In Singapore, the prevalence of UI among community-dwelling older adults was reported as 3.5% in those aged 55 years, 4.8% in those aged 65 years, and 7.9% in those aged 75 years. Although UI is not a life threatening problem, the symptoms of incontinence can cause considerable impairment. A questionnaire like the International Consultation on Incontinence Questionnaire Urinary Incontinence-Short Form (ICIQ-UI SF) is the simplest form of screening for continence status in both the community and primary care settings.