TEG® 6s coagulation testing with a novel heparin neutralization cartridge: Technical validation and determination of normal reference ranges.

Objectives: We sought to establish normal reference ranges (NRRs) for a novel TEG 6s cartridge (TEG 6s Citrated: K, KH, RTH, FFH [Global Hemostasis]) (Haemonetics Corporation, Boston, MA, US).

Methods: Healthy volunteers (≥18 years of age) included in this single-arm study provided single samples of whole blood. Primary end points included TEG parameters in the citrated kaolin (CK), CK with heparinase (CKH), RapidTEG with heparinase (CRTH), and functional fibrinogen with heparinase (CFFH) assays.

Large-scale real-world data analysis of source plasma collections using a novel technology-enabled nomogram.

Background: Source plasma collections are needed to satisfy the growing demand for plasma-derived medicinal products. The US plasma collection target volume has been guided by a standard weight-based FDA-issued nomogram (STAN) since 1992. In this research, large-scale US-based real-world data (RWD) were analyzed to confirm the safety and volume gains of a newly introduced personalized nomogram (PERS) that was previously studied in a premarket randomized controlled environment.

Timing of hypotensive adverse events in U.S. source plasma donors: Exploratory analysis from the IMPACT trial.

Background And Objectives: There is less robust data describing adverse events (AEs) in source plasma donors than in whole blood donors, particularly regarding time to AEs (TAEs). We, therefore, sought to characterize TAE and the influence of donor characteristics in a large-scale clinical trial dataset.

Materials And Methods: TAE was calculated utilizing data from the IMPACT (IMproving PlasmA CollecTion) trial, with linear regression analyses performed to determine the influence of donor parameters on TAE.

HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity.

The novel SARS-CoV-2 coronavirus infection has become a global health concern, causing the COVID-19 pandemic. The disease symptoms and outcomes depend on the host immunity, in which the human leukocyte antigen (HLA) molecules play a distinct role. The HLA alleles have an inter-population variability, and understanding their link to the COVID-19 in an ethnically distinct population may contribute to personalized medicine.

Repeat donation and deferral rates in US source plasma donors: Exploratory analysis from the IMPACT trial.

Background: The IMPACT trial demonstrated the safety of a new personalized nomogram for plasma donation and provided an opportunity to explore short- to mid-term impact on repeat donation and deferral rates, and factors affecting these.

Study Design And Methods: In the IMPACT trial, participants were randomized to donate plasma using an established weight-based nomogram (control) versus a new personalized nomogram incorporating height, weight, and hematocrit (experimental). In this exploratory analysis, repeat donations (per donor, by study arm) were analyzed using negative binomial generalized linear regression models and descriptive statistics.

Personalized collection of plasma from healthy donors: A randomized controlled trial of a novel technology-enabled nomogram.

Background: Source plasma is essential to support the growing demand for plasma-derived medicinal products. Supply is short, with donor availability further limited by the coronavirus disease 2019 (COVID-19) pandemic. This study examined whether a novel, personalized, technology-based nomogram was noninferior with regard to significant hypotensive adverse events (AEs) in healthy donors.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06650833, a selective interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor, in single and multiple ascending dose randomized phase 1 studies in healthy subjects.

Background: PF-06650833 is a potent, selective inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4). Two randomized, double-blind, sponsor-open phase 1 studies evaluated the safety, pharmacokinetics, and pharmacodynamics of single (SAD) and multiple ascending doses (MAD) of PF-06650833 immediate-release (IR) and modified-release (MR) oral formulations in healthy adult subjects.

Methods: Study 1 (NCT02224651) was a 96-day, placebo-substitution, SAD study of once-daily (QD) oral PF-06650833 IR 1 to 6000 mg and MR 30 to 300 mg in fasted and fed states.

Application of Quantitative Pharmacology Approaches in Bridging Pharmacokinetics and Pharmacodynamics of Domagrozumab From Adult Healthy Subjects to Pediatric Patients With Duchenne Muscular Disease.

Domagrozumab, a monoclonal antibody that binds to myostatin, is being developed for Duchenne muscular dystrophy (DMD) boys following a first-in-human study in healthy adults. Literature reporting pharmacokinetic parameters of monoclonal antibodies suggested that body-weight- and body-surface-area-adjusted clearance and volume of distribution estimates between adults and children are similar for subjects older than 6 years. Population modeling identified a Michaelis-Menten binding kinetics model to optimally characterize the target mediated drug disposition profile of domagrozumab and identified body mass index on the volume of distribution as the only significant covariate.

Statistical Monitoring in Clinical Trials: Best Practices for Detecting Data Anomalies Suggestive of Fabrication or Misconduct.

Background: Traditional site-monitoring techniques are not optimal in finding data fabrication and other nonrandom data distributions with the greatest potential for jeopardizing the validity of study results. TransCelerate BioPharma conducted an experiment testing the utility of statistical methods for detecting implanted fabricated data and other signals of noncompliance.

Methods: TransCelerate tested statistical monitoring on a data set from a chronic obstructive pulmonary disease (COPD) clinical study with 178 sites and 1554 subjects.

Fasting glucose and glucose tolerance as potential predictors of neurocognitive function among nondiabetic older adults.

Introduction: Significant evidence has demonstrated that Type 2 diabetes mellitus and related precursors are associated with diminished neurocognitive function and risk of dementia among older adults. However, very little research has examined relations of glucose regulation to neurocognitive function among older adults free of these conditions. The primary aim of this investigation was to examine associations among fasting glucose, glucose tolerance, and neurocognitive function among nondiabetic older adults.

Central site monitoring: results from a test of accuracy in identifying trials and sites failing Food and Drug Administration inspection.

Background: Site monitoring and source document verification account for 15%-30% of clinical trial costs. An alternative is to streamline site monitoring to focus on correcting trial-specific risks identified by central data monitoring. This risk-based approach could preserve or even improve the quality of clinical trial data and human subject protection compared to site monitoring focused primarily on source document verification.

Web-based versus paper administration of common ophthalmic questionnaires: comparison of subscale scores.

Objective: To compare participants' responses to Web-based and paper-and-pencil versions of an ophthalmic, patient-reported outcome (PRO) questionnaire.

Design: Questionnaire development.

Participants: Matched subjects with ocular surface disease (OSD) (n = 68) and without OSD (controls, n = 50).

Interactive relations of blood pressure and age to subclinical cerebrovascular disease.

Objective: To examine interactive relations of blood pressure (BP) and age to MRI indices of subclinical cerebrovascular disease in middle-aged to older adults.

Methods: One hundred and thirteen stroke-free and dementia-free, community-dwelling adults (ages 54-81 years; 65% men; 91% white) engaged in (1) clinical assessment of resting SBP and DBP; (2) MRI rated for periventricular white matter hyperintensities (WMH) and deep WMH silent brain infarction (SBI) and brain atrophy (i.e.

Reduced cerebral blood flow in older men with higher levels of blood pressure.

Objective: To examine relations of blood pressure (BP) with single photon emission computed tomography (SPECT)-derived estimates of cerebral blood flow in older men and women.

Methods: Seventy-four stroke and dementia-free, community-dwelling older adults (ages 54-83 years; 68% men; 91% white) free of major medical, neurological, or psychiatric disease, engaged in clinical assessment of resting SBP and DBP, MRI rated for brain atrophy, and brain single photon emission computed tomography (SPECT) studies with computerized coding of cortical and select subcortical regions of interest.

Results: Given significant interactions of BP and sex with respect to multiple SPECT outcomes, sex-stratified multiple regression models were computed.