Self-reported longitudinal COVID-19 vaccination reactogenicity profiles in persons with multiple sclerosis.

Background: Preventing severe COVID-19 associated outcomes continues to be a priority for persons with multiple sclerosis (PwMS). We previously reported in an interim analysis that short-term reactions to the first and second SARS-CoV-2 vaccines experienced by PwMS were mostly self-limiting and similar to reactions experienced by the general population.

Objectives: First, to report short-term reactogenicity experienced by PwMS in relation to the first through fourth SARS-CoV-2 vaccines.

Engaging Multistakeholder Perspectives to Identify Patient-Centered Research Priorities Regarding Vaccine Uptake Among Adults With Autoimmune Conditions.

Objective: The study objective was to prioritize topics for future patient-centered research to increase uptake of common vaccines, such as for pneumococcal pneumonia, influenza, herpes zoster, human papillomavirus, and severe acute respiratory syndrome coronavirus 2, among adults living with autoimmune conditions.

Methods: A steering committee (SC) was formed that included clinicians, patients, patient advocates, and researchers associated with rheumatic diseases (psoriatic arthritis, rheumatoid arthritis, vasculitis), inflammatory bowel disease, and multiple sclerosis. Through a scoping review and discussions, SC members identified research topics regarding vaccine uptake and/or hesitancy for prioritization.

Web-Based Mindfulness-Based Interventions for Well-being: Randomized Comparative Effectiveness Trial.

Background: Mindfulness can improve overall well-being by training individuals to focus on the present moment without judging their thoughts. However, it is unknown how much mindfulness practice and training are necessary to improve well-being.

Objective: The primary aim of this study was to determine whether a standard 8-session web-based mindfulness-based cognitive therapy (MBCT) program, compared with a brief 3-session mindfulness intervention, improved overall participant well-being.

COVID-19 Vaccination Reactogenicity in Persons With Multiple Sclerosis.

Background And Objectives: There are limited data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine reactogenicity in persons with multiple sclerosis (PwMS) and how reactogenicity is affected by disease-modifying therapies (DMTs). The objective of this retrospective cross-sectional study was to generate real-world multiple sclerosis-specific vaccine safety information, particularly in the context of specific DMTs, and provide information to mitigate specific concerns in vaccine hesitant PwMS.

Methods: Between 3/2021 and 6/2021, participants in iConquerMS, an online people-powered research network, reported SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other) reactions within 24 hours (none, mild, moderate, and severe), DMT use, and other attributes.

Patient-Powered Research Networks of the Autoimmune Research Collaborative: Rationale, Capacity, and Future Directions.

Patient-Powered Research Networks (PPRNs) are US-based registry infrastructures co-created by advocacy groups, patient research partners, academic investigators, and other healthcare stakeholders. Patient-Powered Research Networks collect information directly from patients to conduct and disseminate the results of patient-centered/powered research that helps patients make more informed decisions about their healthcare. Patient-Powered Research Networks gather and utilize real-world data and patient-reported outcomes to conduct comparative effectiveness, safety, and other research, and leverage the Internet to accomplish this effectively and efficiently.

The liver toxicity biomarker study phase I: markers for the effects of tolcapone or entacapone.

The Liver Toxicity Biomarker Study is a systems toxicology approach to discover biomarkers that are indicative of a drug's potential to cause human idiosyncratic drug-induced liver injury. In phase I, the molecular effects in rat liver and blood plasma induced by tolcapone (a "toxic" drug) were compared with the molecular effects in the same tissues by dosing with entacapone (a "clean" drug, similar to tolcapone in chemical structure and primary pharmacological mechanism). Two durations of drug exposure, 3 and 28 days, were employed.

Sample size and statistical power considerations in high-dimensionality data settings: a comparative study of classification algorithms.

Background: data generated using 'omics' technologies are characterized by high dimensionality, where the number of features measured per subject vastly exceeds the number of subjects in the study. In this paper, we consider issues relevant in the design of biomedical studies in which the goal is the discovery of a subset of features and an associated algorithm that can predict a binary outcome, such as disease status. We compare the performance of four commonly used classifiers (K-Nearest Neighbors, Prediction Analysis for Microarrays, Random Forests and Support Vector Machines) in high-dimensionality data settings.

The liver toxicity biomarker study: phase I design and preliminary results.

Drug-induced liver injury (DILI) is the primary adverse event that results in withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in development. The Liver Toxicity Biomarker Study (LTBS) is an innovative approach to investigate DILI because it compares molecular events produced in vivo by compound pairs that (a) are similar in structure and mechanism of action, (b) are associated with few or no signs of liver toxicity in preclinical studies, and (c) show marked differences in hepatotoxic potential. The LTBS is a collaborative preclinical research effort in molecular systems toxicology between the National Center for Toxicological Research and BG Medicine, Inc.

Metabolomics-based systems biology and personalized medicine: moving towards n = 1 clinical trials?

Personalized medicine - defined as customized medical care for each patient's unique condition - in the broader context of personalized health, will make significant strides forward when a systems approach is implemented to achieve the ultimate in disease phenotyping and to create novel therapeutics that address system-wide molecular perturbations caused by disease processes. Combination drug therapies with individualized optimization are likely to become a major focus. Metabolomics incorporates the most advanced approaches to molecular phenotype system readout and provides the ideal theranostic technology platform for the discovery of biomarker patterns associated with healthy and diseased states, for use in personalized health monitoring programs and for the design of individualized interventions.

Lost in translation? Role of metabolomics in solving translational problems in drug discovery and development.

Too few drug discovery projects generate a marketed drug product, often because preclinical studies fail to predict the clinical experience with a drug candidate. Improving the success of preclinical-to-clinical translation is of paramount importance in optimizing the pharmaceutical value chain. Here, we advance the case for a molecular systems approach to crossing the preclinical-to-clinical translational chasm and for metabolomic analysis of readily accessible bodyfluids as a key technology in translational activities.

Innovation: Rescuing drug discovery: in vivo systems pathology and systems pharmacology.

The pharmaceutical industry is currently beleaguered by close scrutiny from the financial community, regulators and the general public. Productivity, in terms of new drug approvals, has generally been falling for almost a decade and the safety of a number of highly successful drugs has recently been brought into question. Here, we discuss whether taking an in vivo systems approach to drug discovery and development could be the paradigm shift that rescues the industry.