scholarly journals The Road towards Polyclonal Anti-SARS-CoV-2 Immunoglobulins (Hyperimmune Serum) for Passive Immunization in COVID-19

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 144
Author(s):  
Daniele Focosi ◽  
Marco Tuccori ◽  
Massimo Franchini
Keyword(s):  
Neutralizing Antibodies ◽  
Passive Immunization ◽  
Spike Protein ◽  
Controlled Trials ◽  
Disease Course ◽  
Early Disease ◽  
Hyperimmune Serum ◽  
The Road ◽  
Randomized Controlled ◽  
Pros And Cons

Effective treatments specific for COVID-19 are still lacking. In the setting of passive immunotherapies based on neutralizing antibodies (nAbs), randomized controlled trials of COVID-19 convalescent plasma (CCP) anti-SARS-CoV-2 Spike protein monoclonal antibodies (mAb), which have been granted emergency use authorization, have suggested benefit in early disease course (less than 72 hours from symptoms and seronegative). Meanwhile, polyclonal immunoglobulins (i.e., hyperimmune serum), derived either from CCP donations or from animals immunized with SARS-CoV-2 antigens, are likely to become the next nAb-derived candidate. We here discuss the pros and cons of hyperimmune serum versus CCP and mAb, and summarize the ongoing clinical trials of COVID-19 hyperimmune sera.

scholarly journals Outcomes of older patients with follicular lymphoma using individual data from 5922 patients in 18 randomized controlled trials

2021 ◽  
Vol 5 (6) ◽  
pp. 1737-1745
Author(s):  
Carla Casulo ◽  
Jesse G. Dixon ◽  
Fang-Shu Ou ◽  
Eva Hoster ◽  
Bruce A. Peterson ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Follicular Lymphoma ◽  
Randomized Controlled Trials ◽  
Age Groups ◽  
Progression Free Survival ◽  
Controlled Trials ◽  
Early Disease ◽  
End Points ◽  
Randomized Controlled ◽  
Disease Outcomes

Abstract Limited data exist to describe the clinical features and outcomes for elderly patients with follicular lymphoma (FL). The Follicular Lymphoma Analysis of Surrogacy Hypothesis (FLASH) group performed a prospectively planned pooled analysis of individual patient data from first-line randomized controlled trials (RCTs) and examined associations between age (≤70 vs >70 years), clinical characteristics, and FL outcomes. We identified 18 multicenter clinical RCTs in the FLASH database that enrolled elderly patients (>70 years). Primary end points were early disease outcomes, CR24 and CR30, and progression-free survival (PFS) at 24 months (PFS24). Secondary end points were PFS and overall survival (OS). We identified 5922 previously untreated FL patients from 18 RCTs. Patients age >70 years (vs ≤70 years) more commonly had elevated lactate dehydrogenase, hemoglobin <12 g/dL, ECOG PS ≥2, and elevated β2-microglobulin. Median follow-up was 5.6 years. Patients >70 years did not differ from patients ≤70 years in rates of CR24, CR30, or PFS24. With a median OS of 14.6 years for all patients, median OS was 7.4 and 15.7 years for patients >70 and ≤70 years of age, respectively (hazard ratio = 2.35; 95% confidence interval = 2.03-2.73; P < .001). Age >70 years was a significant predictor of OS and PFS due to higher rates of death without progression, but not PFS24, CR24, or CR30. FL patients >70 years treated on trials have similar early disease outcomes to younger patients. There is no disease-specific outcome difference between age groups. Age alone should not disqualify patients from standard treatments or RCTs.

scholarly journals Hypnotics and Driving Safety: Meta-Analyses of Randomized Controlled Trials Applying the on-the-Road Driving Test

2006 ◽  
Vol 1 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Joris Verster ◽  
Dieuwke Veldhuijzen ◽  
Alain Patat ◽  
Berend Olivier ◽  
Edmund Volkerts
Keyword(s):  
Randomized Controlled Trials ◽  
Driving Safety ◽  
Controlled Trials ◽  
The Road ◽  
Randomized Controlled ◽  
On The Road ◽  
Meta Analyses

scholarly journals The Road to Toxin-Targeted Therapeutic Antibodies

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Thomas R. Kozel
Keyword(s):  
Neutralizing Antibodies ◽  
Passive Immunization ◽  
Binding Activity ◽  
Antibody Isotype ◽  
Variable Regions ◽  
Content Type ◽  
The Road ◽  
Therapeutic Monoclonal Antibodies

ABSTRACT Once an infection by a toxin-producing bacterium is well established, therapies such as antibiotics that target bacterial growth may have little impact on the ultimate patient outcome. In such cases, toxin-neutralizing antibodies offer an opportunity to block key virulence factors. New work by A. K. Varshney, X. Wang, J. L. Aguilar, M. D. Scharff, and B. C. Fries [mBio 5(3):e01007-14, 2014, doi:10.1128/mBio.01007-14] highlights the role of the antibody isotype in determining the efficacy of toxin-neutralizing antibodies in vivo. Varshney et al. examined the role of antibody isotype for protection in murine models of staphylococcal enterotoxin B (SEB)-induced lethal shock and sepsis produced by SEB-producing Staphylococcus aureus. Murine antibodies of the IgG2a isotype were more protective than antibodies of the IgG1 and IgG2b isotypes that have identical variable regions and binding activity. These results add to the complexity inherent in the selection and optimization of antibodies for anti-infective passive immunization and emphasize the need to use relevant in vivo models to evaluate potential therapeutic monoclonal antibodies.

scholarly journals Navigating through the maze of caesarean myomectomy: generating evidence

2019 ◽  
Vol 8 (11) ◽  
pp. 4646
Author(s):  
Fouzia Zahid A. Khan ◽  
Imose Itua
Keyword(s):  
Reproductive Age ◽  
Controlled Trials ◽  
Evidence Based ◽  
Large Sample Size ◽  
Safe Procedure ◽  
Scientific Databases ◽  
Randomized Controlled ◽  
Benefit Evaluation ◽  
Pros And Cons ◽  
Proven Benefit

Management of myomas during pregnancy and labor is a contested subject so far. Currently no recommended national or international guidelines are in place resulting in conflicted opinion and management variation across the globe. Many obstetricians still discourage its practice due to fear of uncontrolled haemorrhage which may lead to unwanted hysterectomy in a reproductive age. However, some researchers have challenged the conventional perspective and argue that caesarean myomectomy (CM) is a safe procedure. The aim of this study is to examine all aspects of CM with an evaluative lens and to weigh its risk-benefit ratio.  For this purpose, we conducted a literature review of studies, including those from low-resource countries indexed in scientific databases like PubMed, Google Scholar and Scopus. Most recent articles that reported benefits, complications and different techniques to safely perform caesarean myomectomy with proven benefit for the patient were examined thoroughly so that solid evidence on pros and cons of caesarean myomectomy could be generated. There is a dire need to conduct large sample size studies or randomized controlled trials for the risk-benefit evaluation of CM and to produce evidence-based clinical conclusion.

scholarly journals Risk of evolutionary escape from neutralizing antibodies targeting SARS-CoV-2 spike protein

2020 ◽  
Author(s):  
Debra Van Egeren ◽  
Alexander Novokhodko ◽  
Madison Stoddard ◽  
Uyen Tran ◽  
Bruce Zetter ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Passive Immunization ◽  
Spike Protein ◽  
Natural Immunity ◽  
Protein Receptor ◽  
Before And After ◽  
Neutral Genetic Variation ◽  
Escape Mutants

As many prophylactics targeting SARS-CoV-2 are aimed at the spike protein receptor-binding domain (RBD), we examined the risk of immune evasion from previously published RBD-targeting neutralizing antibodies (nAbs). Epitopes for RBD-targeting nAbs overlap one another substantially and can give rise to escape mutants with ACE2 affinities comparable to wild type that still infect cells in vitro. We used evolutionary modeling to predict the frequency of immune escape before and after the widespread presence of nAbs due to vaccines, passive immunization or natural immunity. Our modeling suggests that SARS-CoV-2 mutants with one or two mildly deleterious mutations are expected to exist in high numbers due to neutral genetic variation, and consequently resistance to single or double antibody combinations can develop quickly under positive selection.

scholarly journals Sample size calculations in economic RCTs: following clinical studies?

2018 ◽  
Author(s):  
Sven Gruener
Keyword(s):  
Sample Size ◽  
Clinical Studies ◽  
Sample Size Calculation ◽  
Controlled Trials ◽  
Drug Trials ◽  
Randomized Controlled ◽  
Sample Size Calculations ◽  
Pros And Cons ◽  
Clinical Drug Trials ◽  
Clinical Drug

Clinical studies and economic experiments are often conducted utilizing randomized controlled trials. In contrast to clinical drug trials, sample size calculation has rarely been carried out by experimental economists. Using simple examples for illustration purposes, I discuss pros and cons of using sample size calculations in experimental economics.

Sign in / Sign up

Export Citation Format

Share Document