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1.
Respir Care ; 2022 Jun 07.
Article in English | MEDLINE | ID: covidwho-1879560

ABSTRACT

BACKGROUND: The use of high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) for hypoxemic respiratory failure secondary to coronavirus disease 2019 (COVID-19) are recommended by critical-care guidelines; however, apprehension about viral particle aerosolization and patient self-inflicted lung injury may have limited use. We aimed to describe hospital variation in the use and clinical outcomes of HFNC and NIV for the management of COVID-19. METHODS: This was a retrospective observational study of adults hospitalized with COVID-19 who received supplemental oxygen between February 15, 2020, and April 12, 2021, across 102 international and United States hospitals by using the COVID-19 Registry. Associations of HFNC and NIV use with clinical outcomes were evaluated by using multivariable adjusted hierarchical random-effects logistic regression models. Hospital variation was characterized by using intraclass correlation and the median odds ratio. RESULTS: Among 13,454 adults with COVID-19 who received supplemental oxygen, 8,143 (60%) received nasal cannula/face mask only, 2,859 (21%) received HFNC, 878 (7%) received NIV, 1,574 (12%) received both HFNC and NIV, with 3,640 subjects (27%) progressing to invasive ventilation. The hospital of admission contributed to 24% of the risk-adjusted variation in HFNC and 30% of the risk-adjusted variation in NIV. The median odds ratio for hospital variation of HFNC was 2.6 (95% CI 1.4-4.9) and of NIV was 3.1 (95% CI 1.2-8.1). Among 5,311 subjects who received HFNC and/or NIV, 2,772 (52%) did not receive invasive ventilation and survived to hospital discharge. Hospital-level use of HFNC or NIV were not associated with the rates of invasive ventilation or mortality. CONCLUSIONS: Hospital variation in the use of HFNC and NIV for acute respiratory failure secondary to COVID-19 was great but was not associated with intubation or mortality. The wide variation and relatively low use of HFNC/NIV observed within our study signaled that implementation of increased HFNC/NIV use in patients with COVID-19 will require changes to current care delivery practices. (ClinicalTrials.gov registration NCT04323787.).

2.
Pediatr Infect Dis J ; 2022 May 27.
Article in English | MEDLINE | ID: covidwho-1874025

ABSTRACT

BACKGROUND: Describe the incidence and associated outcomes of gastrointestinal (GI) manifestations of acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in hospitalized children (MIS-C). METHODS: Retrospective review of the Viral Infection and Respiratory Illness Universal Study registry, a prospective observational, multicenter international cohort study of hospitalized children with acute COVID-19 or MIS-C from March 2020 to November 2020. The primary outcome measure was critical COVID-19 illness. Multivariable models were performed to assess for associations of GI involvement with the primary composite outcome in the entire cohort and a subpopulation of patients with MIS-C. Secondary outcomes included prolonged hospital length of stay defined as being >75th percentile and mortality. RESULTS: Of the 789 patients, GI involvement was present in 500 (63.3%). Critical illness occurred in 392 (49.6%), and 18 (2.3%) died. Those with GI involvement were older (median age of 8 yr), and 18.2% had an underlying GI comorbidity. GI symptoms and liver derangements were more common among patients with MIS-C. In the adjusted multivariable models, acute COVID-19 was no associated with the primary or secondary outcomes. Similarly, despite the preponderance of GI involvement in patients with MIS-C, it was also not associated with the primary or secondary outcomes. CONCLUSIONS: GI involvement is common in hospitalized children with acute COVID-19 and MIS-C. GI involvement is not associated with critical illness, hospital length of stay or mortality in acute COVID-19 or MIS-C.

3.
Chest ; 2022 May 18.
Article in English | MEDLINE | ID: covidwho-1850817

ABSTRACT

BACKGROUND: There is urgent need for safe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19. Despite increased adoption during the pandemic, the effectiveness of prone positioning on respiratory failure progression among non-intubated patients is unclear. RESEARCH QUESTION: What is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared to usual care to reduce progression of respiratory failure among non-intubated patients with COVID-19? STUDY DESIGN AND METHODS: APPEX-19 is a multicenter randomized clinical trial that randomized non-intubated adults with COVID-19 on <6 L/minute supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or intensive care unit transfer. Using a Bayesian statistical approach, we calculated the posterior probability of superiority within each treatment arm (superiority threshold 95%). RESULTS: The trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention to treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n=139; 70 intervention; 69 usual care), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean 24.7%, 95% credible interval 18.6-31.4%) receiving usual care and 32 participants (posterior mean 22.1%, 95% credible interval 16.6-28.1%) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and 11.9% of participants in the intervention arm. INTERPRETATION: Among non-intubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning.

6.
World J Crit Care Med ; 11(2): 102-111, 2022 Mar 09.
Article in English | MEDLINE | ID: covidwho-1791995

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) course may be affected by environmental factors. Ecological studies previously suggested a link between climatological factors and COVID-19 fatality rates. However, individual-level impact of these factors has not been thoroughly evaluated yet. AIM: To study the association of climatological factors related to patient location with unfavorable outcomes in patients. METHODS: In this observational analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: COVID-19 Registry cohort, the latitudes and altitudes of hospitals were examined as a covariate for mortality within 28 d of admission and the length of hospital stay. Adjusting for baseline parameters and admission date, multivariable regression modeling was utilized. Generalized estimating equations were used to fit the models. RESULTS: Twenty-two thousand one hundred eight patients from over 20 countries were evaluated. The median age was 62 (interquartile range: 49-74) years, and 54% of the included patients were males. The median age increased with increasing latitude as well as the frequency of comorbidities. Contrarily, the percentage of comorbidities was lower in elevated altitudes. Mortality within 28 d of hospital admission was found to be 25%. The median hospital-free days among all included patients was 20 d. Despite the significant linear relationship between mortality and hospital-free days (adjusted odds ratio (aOR) = 1.39 (1.04, 1.86), P = 0.025 for mortality within 28 d of admission; aOR = -1.47 (-2.60, -0.33), P = 0.011 for hospital-free days), suggesting that adverse patient outcomes were more common in locations further away from the Equator; the results were no longer significant when adjusted for baseline differences (aOR = 1.32 (1.00, 1.74), P = 0.051 for 28-day mortality; aOR = -1.07 (-2.13, -0.01), P = 0.050 for hospital-free days). When we looked at the altitude's effect, we discovered that it demonstrated a non-linear association with mortality within 28 d of hospital admission (aOR = 0.96 (0.62, 1.47), 1.04 (0.92, 1.19), 0.49 (0.22, 0.90), and 0.51 (0.27, 0.98), for the altitude points of 75 MASL, 125 MASL, 400 MASL, and 600 MASL, in comparison to the reference altitude of 148 m.a.s.l, respectively. P = 0.001). We detected an association between latitude and 28-day mortality as well as hospital-free days in this worldwide study. When the baseline features were taken into account, however, this did not stay significant. CONCLUSION: Our findings suggest that differences observed in previous epidemiological studies may be due to ecological fallacy rather than implying a causal relationship at the patient level.

7.
Sci Rep ; 12(1): 5583, 2022 04 04.
Article in English | MEDLINE | ID: covidwho-1773994

ABSTRACT

Neutrophil-mediated secondary tissue injury underlies acute respiratory distress syndrome (ARDS) and progression to multi-organ-failure (MOF) and death, processes linked to COVID-19-ARDS. This secondary tissue injury arises from dysregulated neutrophils and neutrophil extracellular traps (NETs) intended to kill pathogens, but instead cause cell-injury. Insufficiency of pleiotropic therapeutic approaches delineate the need for inhibitors of dysregulated neutrophil-subset(s) that induce subset-specific apoptosis critical for neutrophil function-shutdown. We hypothesized that neutrophils expressing the pro-survival dual endothelin-1/VEGF-signal peptide receptor, DEspR, are apoptosis-resistant like DEspR+ cancer-cells, hence comprise a consequential pathogenic neutrophil-subset in ARDS and COVID-19-ARDS. Here, we report the significant association of increased peripheral DEspR+CD11b+ neutrophil-counts with severity and mortality in ARDS and COVID-19-ARDS, and intravascular NET-formation, in contrast to DEspR[-] neutrophils. We detect DEspR+ neutrophils and monocytes in lung tissue patients in ARDS and COVID-19-ARDS, and increased neutrophil RNA-levels of DEspR ligands and modulators in COVID-19-ARDS scRNA-seq data-files. Unlike DEspR[-] neutrophils, DEspR+CD11b+ neutrophils exhibit delayed apoptosis, which is blocked by humanized anti-DEspR-IgG4S228P antibody, hu6g8, in ex vivo assays. Ex vivo live-cell imaging of Rhesus-derived DEspR+CD11b+ neutrophils showed hu6g8 target-engagement, internalization, and induction of apoptosis. Altogether, data identify DEspR+CD11b+ neutrophils as a targetable 'rogue' neutrophil-subset associated with severity and mortality in ARDS and COVID-19-ARDS.


Subject(s)
COVID-19 , Extracellular Traps , Respiratory Distress Syndrome , Humans , Immunophenotyping , Neutrophils
8.
Lancet Respir Med ; 10(6): 573-583, 2022 06.
Article in English | MEDLINE | ID: covidwho-1740330

ABSTRACT

BACKGROUND: Awake prone positioning has been broadly utilised for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure, but the results from published randomised controlled trials (RCTs) in the past year are contradictory. We aimed to systematically synthesise the outcomes associated with awake prone positioning, and evaluate these outcomes in relevant subpopulations. METHODS: In this systematic review and meta-analysis, two independent groups of researchers searched MEDLINE, Embase, PubMed, Web of Science, Scopus, MedRxiv, BioRxiv, and ClinicalTrials.gov for RCTs and observational studies (with a control group) of awake prone positioning in patients with COVID-19-related acute hypoxaemic respiratory failure published in English from Jan 1, 2020, to Nov 8, 2021. We excluded trials that included patients intubated before or at enrolment, paediatric patients (ie, younger than 18 years), or trials that did not include the supine position in the control group. The same two independent groups screened studies, extracted the summary data from published reports, and assessed the risk of bias. We used a random-effects meta-analysis to pool individual studies. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty and quality of the evidence. The primary outcome was the reported cumulative intubation risk across RCTs, and effect estimates were calculated as risk ratios (RR;95% CI). The analysis was primarily conducted on RCTs, and observational studies were used for sensitivity analyses. No serious adverse events associated with awake prone positioning were reported. The study protocol was prospectively registered with PROSPERO, CRD42021271285. FINDINGS: A total of 1243 studies were identified, we assessed 138 full-text articles and received the aggregated results of three unpublished RCTs; therefore, after exclusions, 29 studies were included in the study. Ten were RCTs (1985 patients) and 19 were observational studies (2669 patients). In ten RCTs, awake prone positioning compared with the supine position significantly reduced the need for intubation in the overall population (RR 0·84 [95% CI 0·72-0·97]). A reduced need for intubation was shown among patients who received advanced respiratory support (ie, high-flow nasal cannula or non-invasive ventilation) at enrolment (RR 0·83 [0·71-0·97]) and in intensive care unit (ICU) settings (RR 0·83 [0·71-0·97]) but not in patients receiving conventional oxygen therapy (RR 0·87 [0·45-1·69]) or in non-ICU settings (RR 0·88 [0·44-1·76]). No obvious risk of bias and publication bias was found among the included RCTs for the primary outcome. INTERPRETATION: In patients with COVID-19-related acute hypoxaemic respiratory failure, awake prone positioning reduced the need for intubation, particularly among those requiring advanced respiratory support and those in ICU settings. Awake prone positioning should be used in patients who have acute hypoxaemic respiratory failure due to COVID-19 and require advanced respiratory support or are treated in the ICU. FUNDING: OpenAI, Rice Foundation, National Institute for Health Research, and Oxford Biomedical Research Centre.


Subject(s)
COVID-19 , Respiratory Insufficiency , COVID-19/complications , Child , Humans , Patient Positioning/methods , Prone Position , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Wakefulness
9.
Clin Endocrinol (Oxf) ; 2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1708522

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID-19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID-19 as well as describe the differences in outcomes between patients with and without pre-existing hypothyroidism using an observational, multinational registry. METHODS: In an observational cohort study we enrolled patients 18 years or older, with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID-19 hospitalization, (2) in-hospital mortality and (3) hospital-free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality. RESULTS: Among the 20,366 adult patients included in the study, pre-existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59-80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre-existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in-hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital-free days (estimated difference 0.01 days; 95% CI: -0.45, 0.47; p = .97). Pre-existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis. CONCLUSIONS: In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID-19. Pre-existing hypothyroidism in hospitalized patients with COVID-19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID-19 on the thyroid gland and its function is needed in the future.

10.
Critical care explorations ; 10(2), 2022.
Article in English | EuropePMC | ID: covidwho-1695890

ABSTRACT

OBJECTIVES: To describe hospital variation in use of “guideline-based care” for acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN: Retrospective, observational study. SETTING: The Society of Critical Care Medicine’s Discovery Viral Infection and RESPIRATORY ILLNESS UNIVERSAL STUDY COVID-19 REGISTRY. PATIENTS: Adult patients with ARDS due to COVID-19 between February 15, 2020, and April 12, 2021. INTERVENTIONS: Hospital-level use of “guideline-based care” for ARDS including low-tidal-volume ventilation, plateau pressure less than 30 cm H2O, and prone ventilation for a Pao2/Fio2 ratio less than 100. MEASUREMENTS AND MAIN RESULTS: Among 1,495 adults with COVID-19 ARDS receiving care across 42 hospitals, 50.4% ever received care consistent with ARDS clinical practice guidelines. After adjusting for patient demographics and severity of illness, hospital characteristics, and pandemic timing, hospital of admission contributed to 14% of the risk-adjusted variation in “guideline-based care.” A patient treated at a randomly selected hospital with higher use of guideline-based care had a median odds ratio of 2.0 (95% CI, 1.1–3.4) for receipt of “guideline-based care” compared with a patient receiving treatment at a randomly selected hospital with low use of recommended therapies. Median-adjusted inhospital mortality was 53% (interquartile range, 47–62%), with a nonsignificantly decreased risk of mortality for patients admitted to hospitals in the highest use “guideline-based care” quartile (49%) compared with the lowest use quartile (60%) (odds ratio, 0.7;95% CI, 0.3–1.9;p = 0.49). CONCLUSIONS: During the first year of the COVID-19 pandemic, only half of patients received “guideline-based care” for ARDS management, with wide practice variation across hospitals. Strategies that improve adherence to recommended ARDS management strategies are needed.

11.
BMC Nephrol ; 23(1): 63, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1690946

ABSTRACT

BACKGROUND: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern. METHODS: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators. RESULTS: Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds. CONCLUSIONS: SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/complications , Inpatients/statistics & numerical data , SARS-CoV-2 , Acute Kidney Injury/etiology , Adolescent , Adult , Age Distribution , Age Factors , Aged , Aged, 80 and over , COVID-19/epidemiology , Child , Child, Preschool , Comorbidity , Confidence Intervals , Creatinine/blood , Global Health/statistics & numerical data , Hospital Mortality , Humans , Middle Aged , Odds Ratio , Registries/statistics & numerical data , Severity of Illness Index
13.
JAMA Netw Open ; 4(12): e2140568, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1592803

ABSTRACT

Importance: Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome. Objective: To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19. Design, Setting, and Participants: This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined as ≥3 of the following criteria: obesity, prediabetes or diabetes, hypertension, and dyslipidemia) and a control population without metabolic syndrome. Participants included adult patients hospitalized for COVID-19 during the study period who had a completed discharge status. Data were analyzed from February 22 to October 5, 2021. Exposures: Exposures were SARS-CoV-2 infection, metabolic syndrome, obesity, prediabetes or diabetes, hypertension, and/or dyslipidemia. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes included ARDS, intensive care unit (ICU) admission, need for invasive mechanical ventilation, and length of stay (LOS). Results: Among 46 441 patients hospitalized with COVID-19, 29 040 patients (mean [SD] age, 61.2 [17.8] years; 13 059 [45.0%] women and 15713 [54.1%] men; 6797 Black patients [23.4%], 5325 Hispanic patients [18.3%], and 16 507 White patients [57.8%]) met inclusion criteria. A total of 5069 patients (17.5%) with metabolic syndrome were compared with 23 971 control patients (82.5%) without metabolic syndrome. In adjusted analyses, metabolic syndrome was associated with increased risk of ICU admission (adjusted odds ratio [aOR], 1.32 [95% CI, 1.14-1.53]), invasive mechanical ventilation (aOR, 1.45 [95% CI, 1.28-1.65]), ARDS (aOR, 1.36 [95% CI, 1.12-1.66]), and mortality (aOR, 1.19 [95% CI, 1.08-1.31]) and prolonged hospital LOS (median [IQR], 8.0 [4.2-15.8] days vs 6.8 [3.4-13.0] days; P < .001) and ICU LOS (median [IQR], 7.0 [2.8-15.0] days vs 6.4 [2.7-13.0] days; P < .001). Each additional metabolic syndrome criterion was associated with increased risk of ARDS in an additive fashion (1 criterion: 1147 patients with ARDS [10.4%]; P = .83; 2 criteria: 1191 patients with ARDS [15.3%]; P < .001; 3 criteria: 817 patients with ARDS [19.3%]; P < .001; 4 criteria: 203 patients with ARDS [24.3%]; P < .001). Conclusions and Relevance: These findings suggest that metabolic syndrome was associated with increased risks of ARDS and death in patients hospitalized with COVID-19. The association with ARDS was cumulative for each metabolic syndrome criteria present.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Hospitalization , Metabolic Syndrome/epidemiology , Respiratory Distress Syndrome/epidemiology , Adult , COVID-19/therapy , Comorbidity , Critical Care , Female , Hospital Mortality , Humans , Length of Stay , Male , Middle Aged , Prognosis , Prospective Studies , Respiration, Artificial , Risk Factors , SARS-CoV-2
15.
Crit Care Explor ; 3(11): e0566, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1505988

ABSTRACT

IMPORTANCE: At the start of the coronavirus disease 2019 pandemic, medications repurposed for management of coronavirus disease 2019 were used in the absence of clinical trial evidence. OBJECTIVES: To describe the variation and evolution in use of repurposed medications for coronavirus disease 2019. DESIGN SETTING AND PARTICIPANTS: Observational cohort study of adults hospitalized with coronavirus disease 2019 between February 15, 2020, and April 12, 2021, across 76 United States and international hospitals within the Society of Critical Care Medicine's Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry. MAIN OUTCOMES AND MEASURES: Hospital variation was quantified using multivariable adjusted random effects logistic regression models and unsupervised clustering. Repurposed medications included antivirals, corticosteroids, hydroxychloroquine, immunomodulators, and therapeutic dose anticoagulants. RESULTS: Among 7,069 adults hospitalized with coronavirus disease 2019, 1,979 (28%) received antivirals, 2,876 (41%) received corticosteroids, 1,779 (25%) received hydroxychloroquine, 620 (9%) received immunomodulators, and 2,154 (31%) received therapeutic dose anticoagulants. Contribution of hospital site to risk-adjusted variation was 46% for antivirals, 30% for corticosteroids, 48% for hydroxychloroquine, 46% for immunomodulators, and 52% for therapeutic dose anticoagulants. Compared with the early pandemic, the later pandemic practice phenotypes converged with increased use of antivirals (odds ratio, 3.14; 95% CI, 2.40-4.10) and corticosteroids (odds ratio, 5.43; 95% CI, 4.23-6.97), with decreased use of hydroxychloroquine (odds ratio, 0.02; 95% CI, 0.01-0.04) and immunomodulators (odds ratio, 0.49; 95% CI, 0.34-0.70). There was no clinically significant change in the use of therapeutic dose anticoagulants (odds ratio, 1.01; 95% CI, 1.01-1.02). There were no differences in risk-adjusted mortality between hospitals with high rates of repurposed medication use compared with hospitals with low rates of use. CONCLUSIONS AND RELEVANCE: Hospital variation in the use of repurposed medications varied widely across hospitals early in the pandemic and later converged with the emergence of randomized clinical trials. Platforms developed for rapid activation and enrollment in clinical trials of repurposed medications are needed prior to the next pandemic to expedite effective, evidence-based practice.

16.
Eur J Med Res ; 26(1): 117, 2021 Oct 02.
Article in English | MEDLINE | ID: covidwho-1448444

ABSTRACT

BACKGROUND: Interleukin-6 receptor antagonists (IL-6RAs) and steroids are emerging immunomodulatory therapies for severe and critical coronavirus disease (COVID-19). In this preliminary report, we aim to describe the epidemiology, clinical characteristics, and outcomes of adult critically ill COVID-19 patients, requiring invasive mechanical ventilation (iMV), and receiving IL-6RA and steroids therapy over the last 11 months. MATERIALS AND METHODS: International, multicenter, cohort study derived from Viral Infection and Respiratory Illness University Study registry and conducted through Discovery Network, Society of Critical Care Medicine. Data were collected between March 01, 2020, and January 10, 2021. RESULTS: Of 860 patients who met eligibility criteria, 589 received steroids, 170 IL-6RAs, and 101 combinations. Patients who received IL-6RAs were younger (median age of 57.5 years vs. 61.1 and 61.8 years in the steroids and combination groups, respectively). The median C-reactive protein level was > 75 mg/L, indicating a hyperinflammatory phenotype. The median daily steroid dose was 7.5 mg dexamethasone or equivalent (interquartile range: 6-14 mg); 80.8% and 19.2% received low-dose and high-dose steroids, respectively. Of the patients who received IL-6RAs, the majority received one dose of tocilizumab and sarilumab (dose range of 600-800 mg for tocilizumab and 200-400 mg for sarilumab). Regarding the timing of administration, we observed that steroid and IL-6RA administration on day 0 of ICU admission was only 55.6% and 39.5%, respectively. By day 28, when compared with steroid use alone, IL-6RA use was associated with an adjusted incidence rate ratio (aIRR) of 1.12 (95% confidence interval [CI] 0.88, 1.4) for ventilator-free days, while combination therapy was associated with an aIRR of 0.83 (95% CI 0.6, 1.14). IL-6RA use was associated with an adjusted odds ratio (aOR) of 0.68 (95% CI 0.44, 1.07) for the 28-day mortality rate, while combination therapy was associated with an aOR of 1.07 (95% CI 0.67, 1.70). Liver dysfunction was higher in IL-6RA group (p = 0.04), while the bacteremia rate did not differ among groups. CONCLUSIONS: Discordance was observed between the registry utilization patterns (i.e., timing of steroids and IL-6RA administration) and new evidence from the recent randomized controlled trials and guideline recommendations. These data will help us to identify areas of improvement in prescribing patterns and enhance our understanding of IL-6RA safety with different steroid regimens. Further studies are needed to evaluate the drivers of hospital-level variation and their impact on clinical outcomes. Trial registration ClinicalTrials.gov: NCT04486521. Registered on July 2020.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/complications , Receptors, Interleukin-6/antagonists & inhibitors , Registries/statistics & numerical data , Respiration, Artificial/methods , Respiratory Insufficiency/mortality , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Critical Illness , Female , Follow-Up Studies , Humans , International Agencies , Male , Middle Aged , Prognosis , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/therapy , Respiratory Insufficiency/virology , Survival Rate , Young Adult
18.
Crit Care Explor ; 3(8): e0514, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1393343

ABSTRACT

IMPORTANCE: Even with its proclivity for older age, coronavirus disease 2019 has been shown to affect all age groups. However, there remains a lack of research focused primarily on the young adult population. OBJECTIVES: To describe the epidemiology and outcomes of coronavirus disease 2019 and identify the risk factors associated with critical illness and mortality in hospitalized young adults. DESIGN SETTINGS AND PARTICIPANTS: A retrospective cohort study of the Society of Critical Care Medicine's Viral Infection and Respiratory Illness Universal Study registry. Patients 18-40 years old, hospitalized from coronavirus disease 2019 from March 2020 to April 2021, were included in the analysis. MAIN OUTCOMES AND MEASURES: Critical illness was defined as a composite of mortality and 21 predefined interventions and complications. Multivariable logistic regression was used to assess associations with critical illness and mortality. RESULTS: Data from 4,005 patients (152 centers, 19 countries, 18.6% non-U.S. patients) were analyzed. The median age was 32 years (interquartile range, 27-37 yr); 51% were female, 29.4% Hispanic, and 42.9% had obesity. Most patients (63.2%) had comorbidities, the most common being hypertension (14.5%) and diabetes (13.7%). Hospital and ICU mortality were 3.2% (129/4,005) and 8.3% (109/1,313), respectively. Critical illness occurred in 25% (n = 996), and 34.3% (n = 1,376) were admitted to the ICU. Older age (p = 0.03), male sex (adjusted odds ratio, 1.83 [95% CI, 1.2-2.6]), and obesity (adjusted odds ratio, 1.6 [95% CI, 1.1-2.4]) were associated with hospital mortality. In addition to the above factors, the presence of any comorbidity was associated with critical illness from coronavirus disease 2019. Multiple sensitivity analyses, including analysis with U.S. patients only and patients admitted to high-volume sites, showed similar risk factors. CONCLUSIONS: Among hospitalized young adults, obese males with comorbidities are at higher risk of developing critical illness or dying from coronavirus disease 2019.

19.
Ann Am Thorac Soc ; 18(9): 1560-1566, 2021 09.
Article in English | MEDLINE | ID: covidwho-1381294

ABSTRACT

The unprecedented public health burdens of coronavirus disease (COVID-19) have intensified the urgency of identifying effective, low-cost treatments that limit the need for advanced life support measures and improve clinical outcomes. However, personal protective equipment and staffing shortages, disease virulence, and infectivity have created significant barriers to traditional clinical trial practices. We present the novel design of a pragmatic, adaptive, multicenter, international, prospective randomized controlled clinical trial evaluating the safety and effectiveness of awake prone positioning in spontaneously breathing patients with COVID-19 (APPEX-19 [Awake Prone Position for Early Hypoxemia in COVID-19]). Key innovations of this trial include 1) a novel smartphone-based communication process that facilitates rapid enrollment and intervention delivery while allowing social distancing and conservation of personal protective equipment, 2) Bayesian response-adaptive randomization to allow preferential assignment to the most effective intervention and expedite trial completion compared with frequentist designs, 3) remote electronic collection of patient-reported outcomes and electronic medical record data, and 4) pragmatic prospective use of patient-reported data and data collected as part of routine clinical care. Clinical trial registered with www.clinicaltrials.gov (NCT04344587).


Subject(s)
COVID-19 , Wakefulness , Bayes Theorem , Humans , Hypoxia , Multicenter Studies as Topic , Prone Position , Prospective Studies , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
20.
Crit Care Med ; 49(3): 437-448, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1298993

ABSTRACT

OBJECTIVES: To describe the outcomes of hospitalized patients in a multicenter, international coronavirus disease 2019 registry. DESIGN: Cross-sectional observational study including coronavirus disease 2019 patients hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between February 15, 2020, and November 30, 2020, according to age and type of organ support therapies. SETTING: About 168 hospitals in 16 countries within the Society of Critical Care Medicine's Discovery Viral Infection and Respiratory Illness University Study coronavirus disease 2019 registry. PATIENTS: Adult hospitalized coronavirus disease 2019 patients who did and did not require various types and combinations of organ support (mechanical ventilation, renal replacement therapy, vasopressors, and extracorporeal membrane oxygenation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was hospital mortality. Secondary outcomes were discharge home with or without assistance and hospital length of stay. Risk-adjusted variation in hospital mortality for patients receiving invasive mechanical ventilation was assessed by using multilevel models with hospitals as a random effect, adjusted for age, race/ethnicity, sex, and comorbidities. Among 20,608 patients with coronavirus disease 2019, the mean (± sd) age was 60.5 (±17), 11,1887 (54.3%) were men, 8,745 (42.4%) were admitted to the ICU, and 3,906 (19%) died in the hospital. Hospital mortality was 8.2% for patients receiving no organ support (n = 15,001). The most common organ support therapy was invasive mechanical ventilation (n = 5,005; 24.3%), with a hospital mortality of 49.8%. Mortality ranged from 40.8% among patients receiving only invasive mechanical ventilation (n =1,749) to 71.6% for patients receiving invasive mechanical ventilation, vasoactive drugs, and new renal replacement therapy (n = 655). Mortality was 39% for patients receiving extracorporeal membrane oxygenation (n = 389). Rates of discharge home ranged from 73.5% for patients who did not require organ support therapies to 29.8% for patients who only received invasive mechanical ventilation, and 8.8% for invasive mechanical ventilation, vasoactive drugs, and renal replacement; 10.8% of patients older than 74 years who received invasive mechanical ventilation were discharged home. Median hospital length of stay for patients on mechanical ventilation was 17.1 days (9.7-28 d). Adjusted interhospital variation in mortality among patients receiving invasive mechanical ventilation was large (median odds ratio 1.69). CONCLUSIONS: Coronavirus disease 2019 prognosis varies by age and level of organ support. Interhospital variation in mortality of mechanically ventilated patients was not explained by patient characteristics and requires further evaluation.


Subject(s)
COVID-19/therapy , Critical Care Outcomes , Hospital Mortality , Hospitalization , Patient Discharge/statistics & numerical data , Registries , Adult , Aged , Extracorporeal Membrane Oxygenation , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Renal Replacement Therapy , Respiration, Artificial , Vasoconstrictor Agents
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