scholarly journals Effectiveness of casirivimab and imdevimab, and sotrovimab during Delta variant surge: a prospective cohort study and comparative effectiveness randomized trial

2021 ◽  
Author(s):  
David T. Huang ◽  
Erin K. McCreary ◽  
J. Ryan Bariola ◽  
Tami E. Minnier ◽  
Richard J. Wadas ◽  
...  
Keyword(s):  
Cohort Study ◽  
Observational Study ◽  
Randomized Trial ◽  
Risk Ratio ◽  
Comparative Effectiveness ◽  
Odds Ratio ◽  
Posterior Probability ◽  
Credible Interval ◽  
Effectiveness Trial ◽  
Reduced Risk

IMPORTANCE The effectiveness of monoclonal antibodies (mAbs), casirivimab and imdevimab, and sotrovimab, for patients with mild to moderate Covid-19 from the Delta variant is unknown. OBJECTIVE To evaluate the effectiveness of mAbs for the Delta variant compared to no treatment, and the comparative effectiveness between mAbs. DESIGN, SETTING, AND PARTICIPANTS Two parallel studies among patients who met Emergency Use Authorization criteria for mAbs from July 14, 2021 to September 29, 2021: i.) prospective observational cohort study comparing mAb treatment to no mAb treatment and, ii.) Bayesian adaptive randomized trial comparing the effectiveness of casirivimab-imdevimab versus sotrovimab. In the observational study, we compared eligible patients who received mAb at an outpatient infusion center at UPMC, to nontreated patients with a positive SARS-CoV-2 test. In the comparative effectiveness trial, we randomly allocated casirivimab-imdevimab or sotrovimab to patients presenting to infusion centers and emergency departments, per system therapeutic interchange policy. EXPOSURE Intravenous mAb per their EUA criteria. MAIN OUTCOMES AND MEASURES For the observational study, risk ratio estimates for hospitalization or death by 28 days were compared between mAb treatment to no mAb treatment using propensity matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospital) within 28 days, where patients who died were assigned -1 day) in a Bayesian cumulative logistic model, adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio <1. Equivalence was defined as a 95% posterior probability that the odds ratio is within a given bound. RESULTS Among 3,558 patients receiving mAb, the mean age was 54 (SD 18 years), 1,511 (43%) were treated in an infusion center, and 450 (13%) were hospitalized or died by day 28. In propensity matched models, mAb treatment was associated with reduced risk of hospitalization or death compared to no treatment (risk ratio (RR)=0.40, 95% CI: 0.28-0.57). Both casirivimab and imdevimab (RR=0.31, 95% CI: 0.20-0.50), and sotrovimab (RR=0.60, 95% CI: 0.37-1.00) reduced hospitalization or death compared to no mAb treatment. Among patients allocated randomly to casirivimab and imdevimab (n=2,454) or sotrovimab (n=1,104), the median hospital-free days were 28 (IQR 28-28) for both groups, 28-day mortality was 0.5% (n=12) and 0.6% (n=7), and hospitalization by day 28 was 12% (n=291) and 12% (n=140), respectively. Compared to casirivimab and imdevimab, the median adjusted odds ratio for hospital-free days was 0.88 (95% credible interval, 0.70-1.11) for sotrovimab. This odds ratio yielded 86% probability of inferiority of sotrovimab versus casirivimab and imdevimab, and 79% probability of equivalence. CONCLUSIONS AND RELEVANCE In non-hospitalized patients with mild to moderate Covid-19 due to the Delta variant, casirivimab and imdevimab and sotrovimab were both associated with a reduced risk of hospitalization or death. The comparative effectiveness of mAbs appeared similar, though prespecified criteria for statistical inferiority or equivalence were not met. TRIAL REGISTRATION ClinicalTrials.gov: NCT04790786

scholarly journals A Learning Health System Randomized Trial of Monoclonal Antibodies for Covid-19

2021 ◽  
Author(s):  
Erin K. McCreary ◽  
J. Ryan Bariola ◽  
Tami Minnier ◽  
Richard J. Wadas ◽  
Judith A. Shovel ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Health System ◽  
Comparative Effectiveness ◽  
Odds Ratio ◽  
Posterior Probability ◽  
Fold Increase ◽  
Odds Ratios ◽  
Primary Analysis ◽  
Link Type ◽  
Learning Health System

ABSTRACTBackgroundNeutralizing monoclonal antibodies (mAb) targeting SARS-CoV-2 decrease hospitalization and death in patients with mild to moderate Covid-19. Yet, their clinical use is limited, and comparative effectiveness is unknown.MethodsWe present the first results of an ongoing, learning health system adaptive platform trial to expand mAb treatment to all eligible patients and evaluate the comparative effectiveness of available mAbs. The trial launched March 10, 2021. Results are reported as of June 25, 2021 due to the U.S. federal decision to pause distribution of bamlanivimab-etesevimab; patient follow-up concluded on July 23, 2021. Patients referred for mAb who met Emergency Use Authorization criteria were provided a random mAb allocation of bamlanivimab, bamlanivimab-etesevimab, or casirivimab-imdevimab with a therapeutic interchange policy. The primary outcome was hospital-free days (days alive and free of hospital) within 28 days, where patients who died were assigned -1 day. The primary analysis was a Bayesian cumulative logistic model of all patients treated at an infusion center or emergency department, adjusting for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio < 1. Equivalence was defined as a 95% posterior probability that the odds ratio is within a given bound.ResultsPrior to trial launch, 3.1% (502) of 16,345 patients who were potentially eligible by an automated electronic health record (EHR) screen received mAb. During the trial period, 23.2% (1,201) of 5,173 EHR-screen eligible patients were treated, a 7.5-fold increase. After including additional referred patients from outside the health system, a total of 1,935 study patients received mAb therapy (128 bamlanivimab, 885 bamlanivimab-etesevimab, 922 casirivimab-imdevimab). Mean age ranged from 55 to 57 years, half were female (range, 53% to 54%), and 17% were Black (range, 12% to 19%). Median hospital–free days were 28 (IQR, 28 to 28) for each mAb group. Hospitalization varied between groups (bamlanivimab, 12.5%; bamlanivimab-etesevimab, 14.7%, casirivimab-imdevimab, 14.3%). Relative to casirivimab-imdevimab, the median adjusted odds ratios were 0.58 (95% credible interval (CI), 0.30 to 1.16) and 0.94 (95% CI, 0.72 to 1.24) for the bamlanivimab and bamlanivimab-etesevimab groups, respectively. These odds ratios yielded 91% and 94% probabilities of inferiority of bamlanivimab versus bamlanivimab-etesevimab and casirivimab-imdevimab respectively, and an 86% probability of equivalence between bamlanivimab-etesevimab and casirivimab-imdevimab, at the prespecified odds ratio bound of 0.25. Twenty-one infusion-related adverse events occurred in 0% (0/128), 1.4% (12/885), and 1.0% (9/922) of patients treated with bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab, respectively.ConclusionIn non-hospitalized patients with mild to moderate Covid-19, bamlanivimab, compared to bamlanivimab-etesevimab and casirivimab-imdevimab, resulted in 91% and 94% probabilities of inferiority with regards to odds of improvement in hospital-free days within 28 days. There was an 86% probability of equivalence between bamlanivimab-etesevimab and casirivimab-imdevimab at an odds ratio bound of 0.25. However, the trial was unblinded early due to federal distribution decisions, and no mAb met prespecified criteria for statistical inferiority or equivalence. (ClinicalTrials.gov, NCT04790786).

Unplanned Transfers From Intermediate Care Units to Intensive Care Units: A Cohort Study

2021 ◽  
Vol 30 (5) ◽  
pp. 397-400
Author(s):  
Joao Gabriel Rosa Ramos ◽  
Gabriel Machado Naus dos Santos ◽  
Marina Chetto Coutinho Bispo ◽  
Renata Cristina de Almeida Matos ◽  
Gil Mario Lopes Santos de Carvalho ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Cohort Study ◽  
Intensive Care ◽  
Observational Study ◽  
Hospital Mortality ◽  
Odds Ratio ◽  
Intermediate Care ◽  
Icu Mortality ◽  
Patient Transfers ◽  
Reason For Admission

This study evaluated unplanned transfers from the intermediate care unit (IMCU) to the intensive care unit (ICU) among urgent admissions. This retrospective, observational study was conducted in 2 ICUs and 1 IMCU. Three patterns of urgent admission were assessed: admissions to the ICU only, admissions to the IMCU only, and admissions to the IMCU with subsequent transfer to the ICU. Of 5296 admissions analyzed, 1396 patients (26.4%) were initially admitted to the IMCU. Of these, 172 (12.3%) were transferred from the IMCU to the ICU. Mortality was higher in patients transferred from the IMCU to the ICU than in the 3900 ICU-only patients (odds ratio, 3.22; 95% CI, 1.52-6.80). Most transfers from the IMCU to the ICU (135; 78.5%) were due to deterioration of the condition for which the patient was admitted. Patient transfers from the IMCU to the ICU were common, were associated with increased hospital mortality, and were mostly due to deterioration in the condition that was the reason for admission.

An Analysis of Dental Implants Survival and Success

2018 ◽  
Vol 69 (9) ◽  
pp. 2465-2466
Author(s):  
Iustin Olariu ◽  
Roxana Radu ◽  
Teodora Olariu ◽  
Andrada Christine Serafim ◽  
Ramona Amina Popovici ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Medical History ◽  
Retrospective Cohort Study ◽  
Odds Ratio ◽  
Retrospective Cohort ◽  
Demographic Data ◽  
Kaplan Meier ◽  
Number Of Patients ◽  
Health Related

Osseointegration of a dental implant may encounter a variety of problems caused by various factors, as prior health-related problems, patients� habits and the technique of the implant inserting. Retrospective cohort study of 70 patients who received implants between January 2011- April 2016 in one dental unit, with Kaplan-Meier method to calculate the probability of implants�s survival at 60 months. The analysis included demographic data, age, gender, medical history, behavior risk factors, type and location of the implant. For this cohort the implants�survival for the first 6 months was 92.86% compared to the number of patients and 97.56% compared to the number of total implants performed, with a cumulative failure rate of 2.43% after 60 months. Failures were focused exclusively on posterior mandible implants, on the percentage of 6.17%, odds ratio (OR) for these failures being 16.76 (P = 0.05) compared with other localisations of implants, exclusively in men with median age of 42 years.

Comparison of Clinical Outcomes of Persons Living With HIV by Enrollment Status in Washington, DC: Evaluation of a Large Longitudinal HIV Cohort Study (Preprint)

2019 ◽  
Author(s):  
Jenevieve Opoku ◽  
Rupali K Doshi ◽  
Amanda D Castel ◽  
Ian Sorensen ◽  
Michael Horberg ◽  
...  
Keyword(s):  
Cohort Study ◽  
Health Outcomes ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Hiv Care ◽  
Disease Stage ◽  
People Living With Hiv ◽  
Hiv Disease ◽  
Persons Living With Hiv ◽  
Living With Hiv

BACKGROUND HIV cohort studies have been used to assess health outcomes and inform the care and treatment of people living with HIV disease. However, there may be similarities and differences between cohort participants and the general population from which they are drawn. OBJECTIVE The objective of this analysis was to compare people living with HIV who have and have not been enrolled in the DC Cohort study and assess whether participants are a representative citywide sample of people living with HIV in the District of Columbia (DC). METHODS Data from the DC Health (DCDOH) HIV surveillance system and the DC Cohort study were matched to identify people living with HIV who were DC residents and had consented for the study by the end of 2016. Analysis was performed to identify differences between DC Cohort and noncohort participants by demographics and comorbid conditions. HIV disease stage, receipt of care, and viral suppression were evaluated. Adjusted logistic regression assessed correlates of health outcomes between the two groups. RESULTS There were 12,964 known people living with HIV in DC at the end of 2016, of which 40.1% were DC Cohort participants. Compared with nonparticipants, participants were less likely to be male (68.0% vs 74.9%, <i>P</i>&lt;.001) but more likely to be black (82.3% vs 69.5%, <i>P</i>&lt;.001) and have a heterosexual contact HIV transmission risk (30.3% vs 25.9%, <i>P</i>&lt;.001). DC Cohort participants were also more likely to have ever been diagnosed with stage 3 HIV disease (59.6% vs 47.0%, <i>P</i>&lt;.001), have a CD4 &lt;200 cells/µL in 2017 (6.2% vs 4.6%, <i>P</i>&lt;.001), be retained in any HIV care in 2017 (72.9% vs 59.4%, <i>P</i>&lt;.001), and be virally suppressed in 2017. After adjusting for demographics, DC Cohort participants were significantly more likely to have received care in 2017 (adjusted odds ratio 1.8, 95% CI 1.70-2.00) and to have ever been virally suppressed (adjusted odds ratio 1.3, 95% CI 1.20-1.40). CONCLUSIONS These data have important implications when assessing the representativeness of patients enrolled in clinic-based cohorts compared with the DC-area general HIV population. As participants continue to enroll in the DC Cohort study, ongoing assessment of representativeness will be required.

scholarly journals Impact of digitally acquired peer diagnostic input on diagnostic confidence in outpatient cases: A pragmatic randomized trial

2020 ◽  
Author(s):  
Elaine C Khoong ◽  
Valy Fontil ◽  
Natalie A Rivadeneira ◽  
Mekhala Hoskote ◽  
Shantanu Nundy ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Randomized Trial ◽  
Odds Ratio ◽  
Primary Outcome ◽  
Mixed Effects ◽  
Regression Analyses ◽  
Diagnostic Confidence ◽  
Diagnostic Uncertainty ◽  
Intervention Impact ◽  
High Uncertainty

Abstract Objective The study sought to evaluate if peer input on outpatient cases impacted diagnostic confidence. Materials and Methods This randomized trial of a peer input intervention occurred among 28 clinicians with case-level randomization. Encounters with diagnostic uncertainty were entered onto a digital platform to collect input from ≥5 clinicians. The primary outcome was diagnostic confidence. We used mixed-effects logistic regression analyses to assess for intervention impact on diagnostic confidence. Results Among the 509 cases (255 control; 254 intervention), the intervention did not impact confidence (odds ratio [OR], 1.46; 95% confidence interval [CI], 0.999-2.12), but after adjusting for clinician and case traits, the intervention was associated with higher confidence (OR, 1.53; 95% CI, 1.01-2.32). The intervention impact was greater in cases with high uncertainty (OR, 3.23; 95% CI, 1.09- 9.52). Conclusions Peer input increased diagnostic confidence primarily in high-uncertainty cases, consistent with findings that clinicians desire input primarily in cases with continued uncertainty.

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