Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup.

Transfusion reactions associated with COVID-19 convalescent plasma in outpatient clinical trials.

Background: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials.

Study Design And Methods: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.

Losartan in hospitalized patients with COVID-19 in North America: An individual participant data meta-analysis.

Background: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) have been hypothesized to benefit patients with COVID-19 via the inhibition of viral entry and other mechanisms. We conducted an individual participant data (IPD) meta-analysis assessing the effect of starting the ARB losartan in recently hospitalized COVID-19 patients.

Methods: We searched ClinicalTrials.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

Background: The COVID-19 convalescent plasma (CCP) viral specific antibody levels that translate into recipient post-transfusion antibody levels sufficient to prevent disease progression is not defined.

Methods: This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup.

Symptom Duration and Resolution With Early Outpatient Treatment of Convalescent Plasma for Coronavirus Disease 2019: A Randomized Trial.

Background: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients.

Methods: We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk.

Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis.

Background: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients.

Methods: We searched ClinicalTrials.

Early Outpatient Treatment for Covid-19 with Convalescent Plasma.

Background: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain.

Methods: In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status.

Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis.

Background: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients.

Methods: We searched ClinicalTrials.

Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma.

Background: The efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain.

Methods: This multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults ≥18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day.

The Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults : A Response-Adaptive, Randomized Clinical Trial.

Background: Vitamin D supplementation may prevent falls in older persons, but evidence is inconsistent, possibly because of dosage differences.

Objective: To compare the effects of 4 doses of vitamin D supplements on falls.

Design: 2-stage Bayesian, response-adaptive, randomized trial.

Dipeptidyl peptidase-4 inhibitors and cardiovascular events in patients with type 2 diabetes, without cardiovascular or renal disease.

Background: Cardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) in patients without cardiovascular or renal disease, a majority of newly diagnosed patients with type 2 diabetes often excluded from clinical trials on this association, is poorly understood. Thus, we investigate the risk of major adverse cardiovascular events (MACE) associated with DPP-4i in low-risk patients with diabetes.

Methods: Using a new-user retrospective cohort derived from IBM MarketScan Commercial Claims and Encounters (2010-2015), we identified patients aged 35-65 with type 2 diabetes, without cardiovascular or renal disease, initiating DPP-4i, sulfonylureas, or metformin.

Escitalopram for agitation in Alzheimer's disease (S-CitAD): Methods and design of an investigator-initiated, randomized, controlled, multicenter clinical trial.

Introduction: Alzheimer's disease (AD) is a disabling, common cause of dementia, and agitation is one of the most common and distressing symptoms for patients with AD. Escitalopram for agitation in Alzheimer's disease (S-CitAD) tests a novel, clinically derived therapeutic approach to treat agitation in patients with AD.

Methods: S-CitAD is a NIH-funded, investigator-initiated, randomized, multicenter clinical trial.

Cardiovascular safety signals with dipeptidyl peptidase-4 inhibitors: A disproportionality analysis among high-risk patients.

Purpose: In 2008, the US Food and Drug Administration (FDA) issued Draft Guidance on investigating cardiovascular risk with oral diabetic drugs, including dipeptidyl peptidase-4 inhibitors (DPP-4i). In 2014, underpowered, post hoc analyses of clinical trials suggested an increased risk of heart failure with the use of these products. As such, we assessed disproportionate reporting of major adverse cardiac events (MACE) among reports for DPP-4i submitted to the FDA Adverse Event Reporting System (FAERS) from 2006 to 2015.

Maximizing the Post-Approval Safety of Flibanserin: A Role for Regulators, Clinicians, and Patients.

In August 2015, the US Food and Drug Administration (FDA) made the controversial decision to approve flibanserin (Addyi®) for women experiencing hypoactive sexual desire disorder. A number of factors contributed to disagreements regarding the FDA's decision, including the product's two prior failed FDA reviews, the unmet need of women with this disorder, extensive advocacy and politicization surrounding the product's relevance to women and sexual health, the potential for widespread off-label use, and the product's tenuous risk/benefit profile. Despite that, attention now shifts to maximizing the safe use of the product, including the optimal means to avoid numerous drug-drug interactions as well as the concomitant use of alcohol, both of which potentiate the risks of dizziness, hypotension, and syncope.