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).

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

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

Generating Knowledge from Best Care: Advancing the Continuously Learning Health System

2016 ◽  
Vol 6 (9) ◽  
Author(s):  
Edward Abraham ◽  
◽  
Carlos Blanco ◽  
Celeste Castillo Lee ◽  
Jennifer B. Christian ◽  
...  
Keyword(s):  
Health System ◽  
Learning Health System

scholarly journals Sustainable generation of patient‐led resources in a learning health system

2021 ◽  
Author(s):  
Jennie David ◽  
Catalina Berenblum Tobi ◽  
Samantha Kennedy ◽  
Alexander Jofriet ◽  
Madeleine Huwe ◽  
...  
Keyword(s):  
Health System ◽  
Learning Health System

Poor social support and loneliness in chronic headache: Prevalence and effect modifiers

Cephalalgia ◽  
2021 ◽  
pp. 033310242110203
Author(s):  
Maria Lurenda Westergaard ◽  
Cathrine Juel Lau ◽  
Karen Allesøe ◽  
Anne Helms Andreasen ◽  
Rigmor Højland Jensen
Keyword(s):  
Social Support ◽  
Odds Ratio ◽  
Chronic Headache ◽  
Medication Overuse ◽  
Odds Ratios ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Self Rated Health ◽  
Poor Social Support ◽  
Very High

Objective To explore the prevalence of poor social support and loneliness among people with chronic headache, and how these might be effect modifiers in the relationships between chronic headache and stress, medication overuse, and self-rated health. Background Poor social support and loneliness are consistently linked to worse health outcomes. There are few epidemiologic studies on their effect on headache. Methods The Danish Capital Region Health Survey, a cross-sectional survey, was conducted in 2017. Participants were asked about headache, pain medication use, social support, loneliness, perceived stress, and self-rated health. Data were accessed from sociodemographic registers. Logistic regression analyses were performed to test for effect modification. Results The response rate was 52.6% (55,185 respondents) and was representative of the target population. People with chronic headache were more likely to report poor social support and loneliness compared to those without chronic headache ( p < 0.0001 for both). Odds ratios for the combination of chronic headache and poor social support were very high for stress (odds ratio 8.1), medication overuse (odds ratio 21.9), and poor self-rated health (odds ratio 10.2) compared to those without chronic headache and with good social support. Those who reported both chronic headache and loneliness had a very high odds ratio for stress (odds ratio 14.4), medication overuse (odds ratio 20.1), and poor self-rated health (odds ratio 15.9) compared to those without chronic headache and low loneliness score. When adjusted for sociodemographic factors, poor social support and loneliness were not significant effect modifiers in almost all these associations. Loneliness was a significant effect modifier in the association between chronic headache and medication overuse, but exerted greater effect among those who did not report they were lonely. Conclusion Poor social support and loneliness were prevalent among people with chronic headache. The combination of chronic headache and poor social support or loneliness showed higher odds ratios for stress, medication overuse, and poor self-rated health compared to those with good social support and low loneliness scores. The effect of loneliness in the relationship between chronic headache and medication overuse warrants further study.

scholarly journals Efficacy of two-week therapy with doxycycline-based quadruple regimen versus levofloxacin concomitant regimen for helicobacter pylori infection: a prospective single-center randomized controlled trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Marouf Alhalabi ◽  
Mohammed Waleed Alassi ◽  
Kamal Alaa Eddin ◽  
Khaled Cheha
Keyword(s):  
Clinical Trial ◽  
Helicobacter Pylori ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Controlled Trial ◽  
Helicobacter Pylori Infection ◽  
First Line ◽  
Link Type ◽  
Syrian Population

Abstract Background Antibiotic-resistance reduces the efficacy of conventional triple therapy for Helicobacter Pylori infections worldwide, which necessitates using various treatment protocols. We used two protocols, doxycycline-based quadruple regimen and concomitant levofloxacin regimen. The aim was to assess the effectiveness of doxycycline-based quadruple regimen for treating Helicobacter Pylori infections compared with levofloxacin concomitant regimen as empirical first-line therapy based on intention-to-treat (ITT) and per-protocol analyses (PPA) in Syrian population. Settings and design An open-label, randomised, parallel, superiority clinical trial. Methods We randomly assigned 78 naïve patients who tested positive for Helicobacter Pylori gastric infection, with a 1:1 ratio to (D-group) which received (bismuth subsalicylate 524 mg four times daily, doxycycline 100 mg, tinidazole 500 mg, and esomeprazole 20 mg, each twice per day for 2 weeks), or (L-group) which received (levofloxacin 500 mg daily, tinidazole 500 mg, amoxicillin 1000 mg, and esomeprazole 20 mg each twice per day for two weeks). We confirmed Helicobacter Pylori eradication by stool antigen test 8 weeks after completing the treatment. Results Thirty-nine patients were allocated in each group. In the D-group, 38 patients completed the follow-up, 30 patients were cured. While in the L-group, 39 completed the follow-up, 32patients were cured. According to ITT, the eradication rates were 76.92%, and 82.05%, for the D-group and L-group respectively. Odds ratio with 95% confidence interval was 1.371 [0.454–4.146]. According to PPA, the eradication rates were 78.9%, and 82.05% for the D-group and L-group respectively. The odds ratio with 95% confidence interval was 1.219 [0.394–3.774]. We didn’t report serious adverse effects. Conclusions Levofloxacin concomitant therapy wasn’t superior to doxycycline based quadruple therapy. Further researches are required to identify the optimal first-line treatment for Helicobacter-Pylori Infection in the Syrian population. Trial registration We registered this study as a standard randomized clinical trial (Clinicaltrial.gov, identifier-NCT04348786, date:29-January-2020).

scholarly journals CGRP-antibodies, topiramate and botulinum toxin type A in episodic and chronic migraine: A systematic review and meta-analysis

Cephalalgia ◽  
2021 ◽  
pp. 033310242110181
Author(s):  
Florian Frank ◽  
Hanno Ulmer ◽  
Victoria Sidoroff ◽  
Gregor Broessner
Keyword(s):  
Systematic Review ◽  
Monoclonal Antibodies ◽  
Botulinum Toxin ◽  
Response Rate ◽  
Meta Analysis ◽  
Botulinum Toxin Type A ◽  
Type A ◽  
Response Rates ◽  
Botulinum Toxin Type ◽  
Odds Ratios

Background The approval of monoclonal antibodies for prevention of migraine has revolutionized treatment for patients. Oral preventatives are still considered first line treatments as head-to-head trials comparing them with antibodies are lacking. Methods The main purpose of this study was to provide a comparative overview of the efficacy of three commonly prescribed migraine preventative medication classes. For this systematic review and meta-analysis, we searched the databases CENTRAL, EMBASE, and MEDLINE until 20 March 2020. We included RCTs reporting the 50% response rates for topiramate, Botulinum Toxin Type A and monoclonal antibodies against CGRP(r). Studies were excluded if response rates were not reported, treatment allocation was unclear, or if study quality was insufficient. Primary outcome measure were the 50% response rates. The pooled odds ratios with 95% confidence intervals were calculated with the random effects model. The study was registered at PROSPERO (CRD42020222880). Findings We identified 6552 reports. Thirty-two were eligible for our review. Studies assessing monoclonal antibodies included 13,302 patients and yielded pooled odds ratios for the 50% response rate of 2.30 (CI: 2.11–2.50). Topiramate had an overall effect estimate of 2.70 (CI: 1.97–3.69) with 1989 included patients and Botulinum Toxin Type A achieved 1.28 (CI: 0.98–1. 67) with 2472 patients included. Interpretation Topiramate, botulinum toxin type A and monoclonal antibodies showed higher odds ratios in achieving a 50% response rate compared to placebo. Topiramate numerically demonstrated the greatest effect size but also the highest drop-out rate.

scholarly journals Fetal CHD and perinatal outcomes

2020 ◽  
Vol 30 (5) ◽  
pp. 686-691
Author(s):  
Christina J. Ge ◽  
Amanda C. Mahle ◽  
Irina Burd ◽  
Eric B. Jelin ◽  
Priya Sekar ◽  
...  
Keyword(s):  
Cohort Study ◽  
Preterm Delivery ◽  
Odds Ratio ◽  
Retrospective Cohort ◽  
Mode Of Delivery ◽  
Perinatal Outcomes ◽  
Fold Increase ◽  
Cesarean Sections ◽  
Increased Risk ◽  
Gestational Age At Delivery

AbstractObjective:To evaluate delivery management and outcomes in fetuses prenatally diagnosed with CHD.Study design:A retrospective cohort study was conducted on 6194 fetuses (born between 2013 and 2016), comparing prenatally diagnosed with CHD (170) to those with non-cardiac (234) and no anomalies (5790). Primary outcomes included the incidence of preterm delivery and mode of delivery.Results:Gestational age at delivery was significantly lower between the CHD and non-anomalous cohorts (38.6 and 39.1 weeks, respectively). Neonates with CHD had a significantly lower birth weights (p < 0.001). There was an approximately 1.5-fold increase in the rate of primary cesarean sections associated with prenatally diagnosed CHD with an odds ratio of 1.49 (95% CI 1.06–2.10).Conclusions:Our study provides additional evidence that the prenatal diagnosis of CHD is associated with a lower birth weight, preterm delivery, and with an increased risk of delivery by primary cesarean section.

scholarly journals Estado nutricional e maturação sexual de adolescentes de uma escola pública e de uma escola privada do Município do Rio de Janeiro

2005 ◽  
Vol 18 (2) ◽  
pp. 183-191 ◽  
Author(s):  
Celina Szuchmacher Oliveira ◽  
Glória Valéria da Veiga
Keyword(s):  
Odds Ratio ◽  
Rio De Janeiro ◽  
Odds Ratios

OBJETIVO: Avaliar o estado nutricional e a maturação sexual de adolescentes de 11 a 15,9 anos, de níveis socioeconômicos diferentes. MÉTODOS: Foram avaliados 303 estudantes de uma escola pública e 199 de uma escola privada do município do Rio de Janeiro. O estado nutricional foi avaliado por meio do índice de massa corporal e dobras cutâneas tricipital e subescapular. Avaliou-se a maturação sexual, por intermédio de auto-avaliação, para identificação de estágio de desenvolvimento de mama e genitália externa. RESULTADOS: Na escola pública, observou-se que 2,0% dos adolescentes tinham baixo peso, 6,6% sobrepeso e 9,2% eram obesos. Na escola privada, as respectivas freqüências foram 3,0%, 9,0% e 18,1%, sem diferença entre os sexos. Na escola privada, maior número de meninas apresentava sobrepeso/obesidade (27,1% vs 14,2%; chi2=8,08, p=0,004), e maior número de meninos e meninas estavam em estágios mais avançados de maturação sexual do que os da escola pública. O risco de apresentar sobrepeso/obesidade foi maior nas adolescentes em estágios mais avançados de maturação sexual (Odds ratio=3,16, intervalos de confiança de 95,0% 1,71-5,87). Esta associação foi observada apenas nos adolescentes da escola pública (Odds ratios=3,52 intervalos de confiança 95,0% 1,76-7,07). CONCLUSÃO: A obesidade foi o problema nutricional mais relevante entre os adolescentes. Nos estudantes da escola pública, o processo de maturação sexual foi mais tardio do que nos da escola privada.

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