Data cleaning and harmonization of clinical trial data: Medication-assisted treatment for opioid use disorder.

Several large-scale, pragmatic clinical trials on opioid use disorder (OUD) have been completed in the National Drug Abuse Treatment Clinical Trials Network (CTN). However, the resulting data have not been harmonized between the studies to compare the patient characteristics. This paper provides lessons learned from a large-scale harmonization process that are critical for all biomedical researchers collecting new data and those tasked with combining datasets.

Empirically contrasting urine drug screening-based opioid use disorder treatment outcome definitions.

Background And Aims: A lack of consensus on the optimal outcome measures to assess opioid use disorder (OUD) treatment efficacy and their precise definition and computation has hampered the pooling of research data for evidence synthesis and meta-analyses. This study aimed to empirically contrast multiple clinical trial definitions of treatment success by applying them to the same dataset.

Methods: Data analysis used a suite of functions, developed as a software package for the R language, to operationalize 61 treatment outcome definitions based on urine drug screening (UDS) results.

Individual-Level Risk Prediction of Return to Use During Opioid Use Disorder Treatment.

Importance: No existing model allows clinicians to predict whether patients might return to opioid use in the early stages of treatment for opioid use disorder.

Objective: To develop an individual-level prediction tool for risk of return to use in opioid use disorder.

Design, Setting, And Participants: This decision analytical model used predictive modeling with individual-level data harmonized in June 1, 2019, to October 1, 2022, from 3 multicenter, pragmatic, randomized clinical trials of at least 12 weeks' duration within the National Institute on Drug Abuse Clinical Trials Network (CTN) performed between 2006 and 2016.

Biomarkers for Duchenne muscular dystrophy progression: impact of age in the mdx tongue spared muscle.

Background: Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy without an effective treatment, caused by mutations in the DMD gene, leading to the absence of dystrophin. DMD results in muscle weakness, loss of ambulation, and death at an early age. Metabolomics studies in mdx mice, the most used model for DMD, reveal changes in metabolites associated with muscle degeneration and aging.

Capturing drug use patterns at a glance: An n-ary word sufficient statistic for repeated univariate categorical values.

Introduction: The efficacy of treatments for substance use disorders (SUD) is tested in clinical trials in which participants typically provide urine samples to detect whether the person has used certain substances via urine drug screenings (UDS). UDS data form the foundation of treatment outcome assessment in the vast majority of SUD clinical trials. However, existing methods to calculate treatment outcomes are not standardized, impeding comparability between studies and prohibiting reproducibility of results.

Biomarkers for Duchenne muscular dystrophy progression: impact of age in the mdx tongue spared muscle.

Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy without an effective treatment, caused by mutations in the gene, leading to the absence of dystrophin. DMD results in muscle weakness, loss of ambulation and death at an early age. Metabolomics studies in mice, the most used model for DMD, reveal changes in metabolites associated with muscle degeneration and aging.

No evidence of accelerated epigenetic aging among black heroin users: A case vs control analysis.

This study sought to assess the association between illicit opioid use and accelerated epigenetic aging (A.K.A.

Evaluating the effect of acute diesel exhaust particle exposure on P-glycoprotein efflux transporter in the blood-brain barrier co-cultured with microglia.

A growing public health concern, chronic Diesel Exhaust Particle (DEP) exposure is a heavy risk factor for the development of neurodegenerative diseases like Alzheimer's (AD). Considered the brain's first line of defense, the Blood-Brain Barrier (BBB) and perivascular microglia work in tandem to protect the brain from circulating neurotoxic molecules like DEP. Importantly, there is a strong association between AD and BBB dysfunction, particularly in the Aβ transporter and multidrug resistant pump, P-glycoprotein (P-gp).

Cell based dATP delivery as a therapy for chronic heart failure.

Transplanted human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) improve ventricular performance when delivered acutely post-myocardial infarction but are ineffective in chronic myocardial infarction/heart failure. 2'-deoxy-ATP (dATP) activates cardiac myosin and potently increases contractility. Here we engineered hPSC-CMs to overexpress ribonucleotide reductase, the enzyme controlling dATP production.

Risk of Experiencing an Overdose Event for Patients Undergoing Treatment With Medication for Opioid Use Disorder.

Objective: Overdose risk during a course of treatment with medication for opioid use disorder (MOUD) has not been clearly delineated. The authors sought to address this gap by leveraging a new data set from three large pragmatic clinical trials of MOUD.

Methods: Adverse event logs, including overdose events, from the three trials (N=2,199) were harmonized, and the overall risk of having an overdose event in the 24 weeks after randomization was compared for each study arm (one methadone, one naltrexone, and three buprenorphine groups), using survival analysis with time-dependent Cox proportional hazard models.

Micro-dystrophin gene therapy demonstrates long-term cardiac efficacy in a severe Duchenne muscular dystrophy model.

Micro-dystrophin gene replacement therapies for Duchenne muscular dystrophy (DMD) are currently in clinical trials, but have not been thoroughly investigated for their efficacy on cardiomyopathy progression to heart failure. We previously validated Fiona/dystrophin-utrophin-deficient (dko) mice as a DMD cardiomyopathy model that progresses to reduced ejection fraction indicative of heart failure. Adeno-associated viral (AAV) vector delivery of an early generation micro-dystrophin prevented cardiac pathology and functional decline through 1 year of age in this new model.

Specific polysubstance use patterns predict relapse among patients entering opioid use disorder treatment.

Introduction: While polysubstance use has consistently been associated with higher rates of relapse, few studies have examined subgroups with specific combinations and time course of polysubstance use (i.e., polysubstance use patterns).

The effect of changing the military's sexual assault laws on law enforcement investigative findings in the U.S. Army.

Objective: In 2007, Congress changed the military's sexual assault laws as part of an effort to improve sexual assault case processing. This study looked at the U.S.

PathwayMultiomics: An R Package for Efficient Integrative Analysis of Multi-Omics Datasets With Matched or Un-matched Samples.

Recent advances in technology have made multi-omics datasets increasingly available to researchers. To leverage the wealth of information in multi-omics data, a number of integrative analysis strategies have been proposed recently. However, effectively extracting biological insights from these large, complex datasets remains challenging.

Lessons Learned From Miami-Dade County's COVID-19 Epidemic: Making Surveillance Data Accessible for Policy Makers.

Introduction: COVID-19 represents an unprecedented challenge to policy makers as well as those entrusted with capturing, monitoring, and analyzing COVID-19 data. Effective public policy is data-informed policy. This requires a liaison between public health scientists and public officials.

Evaluating the endothelial-microglial interaction and comprehensive inflammatory marker profiles under acute exposure to ultrafine diesel exhaust particles in vitro.

Exposure to combustion-derived particulate matter (PM) such as diesel exhaust particles (DEP) is a public health concern because people in urban areas are continuously exposed, and once inhaled, fine and ultrafine DEP may reach the brain. The blood-brain barrier (BBB) endothelial cells (EC) and the perivascular microglia protect the brain from circulating pathogens and neurotoxic molecules like DEP. While the BBB-microglial interaction is critical for maintaining homeostasis, no study has previously evaluated the endothelial-microglial interaction nor comprehensively characterized these cells' inflammatory marker profiles under ultrafine DEP exposures in vitro.

Micro-dystrophin gene therapy prevents heart failure in an improved Duchenne muscular dystrophy cardiomyopathy mouse model.

Gene replacement for Duchenne muscular dystrophy (DMD) with micro-dystrophins has entered clinical trials, but efficacy in preventing heart failure is unknown. Although most patients with DMD die from heart failure, cardiomyopathy is undetectable until the teens, so efficacy from trials in young boys will be unknown for a decade. Available DMD animal models were sufficient to demonstrate micro-dystrophin efficacy on earlier onset skeletal muscle pathology underlying loss of ambulation and respiratory insufficiency in patients.

Perceived Risk of Weekly Cannabis Use, Past 30-Day Cannabis Use, and Frequency of Cannabis Use Among Pregnant Women in the United States.

Background: While accumulated evidence has shown that the prevalence of cannabis use among pregnant women in the US has increased in recent years, little is known about the specific subpopulations affected. The aim of this study was to estimate the prevalence and correlates of the perceived risk of weekly cannabis use, past 30-day cannabis use, and frequency of past 30-day cannabis use among US pregnant women.

Methods: We analyzed data from 2,247 pregnant women 14 to 44 years of age surveyed in the 2015 to 2017 cross-sectional National Survey on Drug Use and Health.

Microutrophin expression in dystrophic mice displays myofiber type differences in therapeutic effects.

Gene therapy approaches for DMD using recombinant adeno-associated viral (rAAV) vectors to deliver miniaturized (or micro) dystrophin genes to striated muscles have shown significant progress. However, concerns remain about the potential for immune responses against dystrophin in some patients. Utrophin, a developmental paralogue of dystrophin, may provide a viable treatment option.

PathwayPCA: an R/Bioconductor Package for Pathway Based Integrative Analysis of Multi-Omics Data.

The authors present pathwayPCA, an R/Bioconductor package for integrative pathway analysis that utilizes modern statistical methodology, including supervised and adaptive, elastic-net, sparse principal component analysis. pathwayPCA can be applied to continuous, binary, and survival outcomes in studies with multiple covariates and/or interaction effects. It outperforms several alternative methods at identifying disease-associated pathways in integrative analysis using both simulated and real datasets.

Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine Triphosphate.

Mutations in the gene encoding for dystrophin leads to structural and functional deterioration of cardiomyocytes and is a hallmark of cardiomyopathy in Duchenne muscular dystrophy (DMD) patients. Administration of recombinant adeno-associated viral vectors delivering microdystrophin or ribonucleotide reductase (RNR), under muscle-specific regulatory control, rescues both baseline and high workload-challenged hearts in an aged, DMD mouse model. However, only RNR treatments improved both systolic and diastolic function under those conditions.

coMethDMR: accurate identification of co-methylated and differentially methylated regions in epigenome-wide association studies with continuous phenotypes.

Recent technology has made it possible to measure DNA methylation profiles in a cost-effective and comprehensive genome-wide manner using array-based technology for epigenome-wide association studies. However, identifying differentially methylated regions (DMRs) remains a challenging task because of the complexities in DNA methylation data. Supervised methods typically focus on the regions that contain consecutive highly significantly differentially methylated CpGs in the genome, but may lack power for detecting small but consistent changes when few CpGs pass stringent significance threshold after multiple comparison.