Chronic overlapping pain conditions in individuals with active opioid use disorder: a descriptive study of syringe program participants.

Background: Comorbidity between opioid use disorder (OUD) and chronic pain is substantial. Pain has been shown to be a motivator for OUD onset, maintenance, relapse, and treatment delay. A cluster of pain conditions known as chronic overlapping pain conditions (COPCs), also now referred to in contemporary ICD classification as primary pain conditions, are particularly refractory to traditional forms of pain treatment, and likely adversely impact comorbid OUD.

Real-world prescribing in accordance to ACC/AHA guidelines for lipid-lowering therapy in high-risk primary and secondary prevention of ASCVD: Real-World Prescribing for Lipid-Lowering Therapy.

Objective: The value of lipid lowering therapy (LLT) for prevention of atherosclerotic cardiovascular disease (ASCVD) is well understood. American College of Cardiology and American Heart Association guidelines recommend statin therapy for secondary and high-risk primary ASCVD prevention. Prior studies have identified incomplete uptake of these guidelines in specific practice settings or patient populations.

Baseline characteristics of participants in the Biomarkers for Evaluating Spine Treatments clinical trial: a sequential multiple assignment randomized trial for chronic low back pain†.

Objective: Chronic low back pain (cLBP) is a significant public health problem in the United States. A method to identify treatments that are most likely effective for an individual patient based on their unique characteristics is needed.

Methods: The Biomarkers for Evaluating Spine Treatments (BEST) Trial is a sequential, multiple assignment, randomized trial designed to estimate an optimal treatment or combination of treatments to reduce pain intensity and interference at 24 weeks in individuals with cLBP.

The importance of carbonatite lavas in outgassing Venus' modern-day atmosphere.

Venus diverged from Earth's evolutionary path through the development of a carbon dioxide (CO)-dominated atmosphere, although studies dispute whether this atmosphere arose shortly after accretion or after a protracted period of surface habitability. Widespread volcanic features suggest that volcanic outgassing may have played a pivotal role in the transformation of Venus. However, the formation of volcanic units on Venus by basaltic lavas can only outgas a minor fraction of the CO in the current atmosphere.

Respiratory and Other Infections Following COVID.

Background: One hypothesis for the respiratory syncytial virus (RSV) surge in 2022 was suppression of immune responses following SARS-CoV-2 infection. Our objective was to compare the risk of subsequent RSV and other infections among children with and without SARS-CoV-2 infection.

Methods: We conducted a retrospective cohort study using electronic health record data from 27 US health systems analyzing children aged under 5 years with SARS-CoV-2 infection (test/coded) between March and July 2022.

Risk of neuropsychiatric and related conditions associated with SARS-CoV-2 infection: a difference-in-differences analysis.

The COVID-19 pandemic has been associated with increased neuropsychiatric conditions in children and youths, with evidence suggesting that SARS-CoV-2 infection may contribute additional risks beyond pandemic stressors. This study aims to assess the full spectrum of neuropsychiatric conditions in COVID-19 positive children (ages 5-12) and youths (ages 12-20) compared to a matched COVID-19 negative cohort, accounting for factors influencing infection risk. Using EHR data from 25 institutions in the RECOVER program, we conduct a retrospective analysis of 326,074 COVID-19 positive and 887,314 negative participants matched for risk factors and stratified by age.

Widespread Pain Moderates the Response to Centrally-Acting Therapies in an Observational Cohort of Patients With Urologic Chronic Pelvic Pain Syndrome: A MAPP Research Network Study.

Purpose: Urologic Chronic Pelvic Pain Syndrome (UCPPS) impacts millions of people in the United States but treatment options remain largely unsatisfying. A large number of neurobiological studies from the Multidisciplinary Approach to the study of chronic Pelvic Pain (MAPP) research network and others point to aberrant pain mechanisms in patients with UCPPS and widespread pain, but the clinical significance of widespread pain has been speculative.

Materials And Methods: In the current exploratory study we investigated whether pain and urologic symptoms responded to centrally-directed therapies (tricyclic antidepressants/gabapentinoids) versus peripherally-directed (pelvic floor physical therapy/hydrodistension) therapies depending on the presence or absence of widespread pain when the new treatment was initiated.

Pictorial representation of illness and self measure (PRISM): A putative transdiagnostic tool for evaluating therapeutic effects of psychedelic treatments.

Background: Patients with refractory conditions often identify themselves with their illness, which affects multiple aspects of their lives. The pictorial representation of illness and self measure (PRISM) is a tool used to assess the enmeshment of individuals' perception of self with a particular medical condition, broadly termed self-condition enmeshment.

Aims: This study aimed to evaluate changes in PRISM scores and how these changes relate to symptom changes following naturalistic psychedelic use.

Eltrombopag in combination with immunosuppressive therapy in pediatric severe aplastic anemia: phase 2 ESCALATE trial.

Severe aplastic anemia (SAA) is a rare, life-threatening disease with acquired pancytopenia and hypocellular bone marrow. ESCALATE evaluated eltrombopag in combination with immunosuppressive therapy (IST) in pediatric patients (aged 1 to <18 years) with relapsed/refractory (R/R) or treatment-naïve SAA. The eltrombopag starting dose was 25 mg/d for patients aged 1 to <6 years and 50 mg/d for patients aged 6 to <18 years; dose modifications (maximum dose, 150 mg/d) were allowed to achieve a target platelet count of 50 × 109/L to 200 × 109/L.

Towards precision medicine in clinical trials for the treatment of urologic chronic pelvic pain syndrome: lessons from the MAPP Research Network.

Randomized clinical trials have resulted in few approved therapies for the treatment of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively referred to as urologic chronic pelvic pain syndrome. Heterogenous patient populations, mismatches of treatments to patient phenotypes, non-specific outcomes and use of standard study designs not leveraging phenotypic heterogeneity might have contributed to the inability of previous trials to demonstrate existing efficacy. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network has identified important phenotypic characteristics associated with differential symptom severity and treatment responsiveness.

Cardiovascular post-acute sequelae of SARS-CoV-2 in children and adolescents: cohort study using electronic health records.

The risk of cardiovascular outcomes following SARS-CoV-2 infection has been reported in adults, but evidence in children and adolescents is limited. This paper assessed the risk of a multitude of cardiac signs, symptoms, and conditions 28-179 days after infection, with outcomes stratified by the presence of congenital heart defects (CHDs), using electronic health records (EHR) data from 19 children's hospitals and health institutions from the United States within the RECOVER consortium between March 2020 and September 2023. The cohort included 297,920 SARS-CoV-2-positive individuals and 915,402 SARS-CoV-2-negative controls.

Kidney Function Following COVID-19 in Children and Adolescents.

Importance: It remains unclear whether children and adolescents with SARS-CoV-2 infection are at heightened risk for long-term kidney complications.

Objective: To investigate whether SARS-CoV-2 infection is associated with an increased risk of postacute kidney outcomes among pediatric patients, including those with preexisting kidney disease or acute kidney injury (AKI).

Design, Setting, And Participants: This retrospective cohort study used data from 19 health institutions in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) initiative from March 1, 2020, to May 1, 2023 (follow-up ≤2 years completed December 1, 2024; index date cutoff, December 1, 2022).

Pediatric Long COVID Subphenotypes: An EHR-based study from the RECOVER program.

Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions using electronic health record data from 38 institutions and used an unsupervised machine learning-based approach to identify subphenotypes. Our method, an extension of the Phe2Vec algorithm, uses tens of thousands of clinical concepts from multiple domains to represent patients' clinical histories to then identify groups of patients with similar presentations.

The design and rationale of the Biomarkers for Evaluating Spine Treatments trial: a sequential multiple assignment randomized trial.

Objective: Chronic low back pain (cLBP) is a common condition that impacts quality of life and function. There are many evidence-based treatments to address cLBP; however, treatment effects are modest, perhaps in part due to individual variation in treatment response. The Biomarkers for Evaluating Spine Treatments (BEST) trial was designed as the collaborative centerpiece of the Back Pain Consortium (BACPAC) research program.

Reinfection with SARS-CoV-2 in the Omicron Era is Associated with Increased Risk of Post-Acute Sequelae of SARS-CoV-2 Infection: A RECOVER-EHR Cohort Study.

Importance: Post-acute sequelae of SARS-CoV-2 infection (PASC) remains a major public health challenge. While previous studies have focused on characterizing PASC and identifying its subphenotypes in children and adolescents following an initial SARS-CoV-2 infection, the risks of PASC with Omicron-variant reinfections remain unclear. Using a real-world data approach, this study investigates the risks of PASC following reinfections during the Omicron phase in the pediatric population.

Ex vivo modification of hematopoietic stem and progenitor cells for gene therapy.

The development of viral vectors has been particularly critical for genetic therapies of hematological diseases. Before the development of retrovirus vectors (RVVs), gene transfer into mammalian cells was accomplished by transduction of DNA plasmids by chemical means and later by electroporation. The main limitation of these methods is the inefficiency of transfer of intact sequences, and particularly with electroporation significant cell death of the manipulated cells.

Scientific Advancements in Gene Therapies: Opportunities for Global Regulatory Convergence.

On 4 September 2024, the Reagan-Udall Foundation for the FDA (FDA Foundation) in collaboration with the Food and Drug Administration (FDA) and the Gates Foundation hosted a workshop titled "Scientific Advancements in Gene Therapies: Opportunities for Global Regulatory Convergence". The event brought together a diverse group of experts, including international regulatory bodies, regulated industries, healthcare professionals, patients, academic researchers and global health advocates, to discuss the rapid advancements in gene therapy and the pressing need for equitable access in low-and middle-income countries (LMICs), with sickle cell disease (SCD) serving as the model disorder for the discussions. Although there has been significant progress in gene therapy, such as breakthroughs in clustered regularly interspaced short palindromic repeats (CRISPR)-based technologies and FDA-approved therapies, access to these therapies remain limited in underresourced regions.

Development of self-report measures of physical, mental, and emotional fatigability: the michigan fatigability index (MIFI).

Purpose: To develop item banks and static short-forms for a patient reported outcome measure of perceived physical, mental, and emotional fatigability-the Michigan Fatigability Index (MIFI).

Methods: Building on earlier qualitative work, this study utilized cognitive interviews in samples representing the general adult population across the lifespan, people with multiple sclerosis (MS), or people with fibromyalgia (FM) to develop initial item pools. A nationwide cross-sectional survey study in MS and FM samples was used to field test items to develop item banks.

Vaccine Effectiveness Among 5- to 17-year-old Individuals with Prior SARS-CoV-2 Infection: An EHR-Based Target Trial Emulation Study from the RECOVER Project.

Importance: Prior studies have demonstrated the effectiveness of COVID-19 vaccines in children and adolescents. However, the benefits of vaccination in these age groups with prior infection remain underexplored.

Objective: To evaluate the effectiveness of COVID-19 vaccination in preventing reinfection with various Omicron subvariants (BA.

Pediatric Gastrointestinal Tract Outcomes During the Postacute Phase of COVID-19.

Importance: The profile of gastrointestinal (GI) tract outcomes associated with the postacute and chronic phases of COVID-19 in children and adolescents remains unclear.

Objective: To investigate the risks of GI tract symptoms and disorders during the postacute (28-179 days after documented SARS-CoV-2 infection) and the chronic (180-729 days after documented SARS-CoV-2 infection) phases of COVID-19 in the pediatric population.

Design, Setting, And Participants: This retrospective cohort study was performed from March 1, 2020, to September 1, 2023, at 29 US health care institutions.

Pressure pain threshold and perceived impact of pain differentially predict short-term and long-term pain reduction following acupuncture in fibromyalgia.

Objective: Acupuncture has demonstrated efficacy as a treatment for fibromyalgia; however, predictors of short- and long-term analgesic response in this population are not well understood.

Methods: This manuscript describes a secondary analysis of a single-center, blinded, sham-controlled, randomized longitudinal acupuncture clinical trial in fibromyalgia. Baseline characterization included pressure pain threshold and pain interference, while residualized change in pain intensity from baseline to follow-up served as the primary outcome measure.

High-impact Chronic Pain in a Cohort of Urologic Chronic Pelvic Pain Syndrome Patients: A Retrospective MAPP Research Network Study.

Objectives: An emerging concept in the chronic pain literature, high-impact chronic pain (HICP), refers to pain that occurs very frequently and results in major disruption of daily life. Previous epidemiologic investigations have noted that lower educational attainment, age, and race appear to be associated with the frequency of HICP, but condition-specific investigations of HICP have been less common.

Materials And Methods: Here we investigate HICP status and its clinical/demographic correlates in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network symptom pattern study.

Feasibility pilot of a novel coaching intervention to optimize cannabis use for chronic pain management among Veterans.

Introduction: Chronic pain is common among Veterans, some of whom use cannabis for pain. We conducted a feasibility pilot study of a novel coaching intervention to help Veterans optimize use of medical cannabis products for pain management (NCT06320470).

Methods: The intervention drew from scientific literature, consultation with cannabis experts, Veteran input via a Community Advisory Board, and tenets of motivational interviewing.

Racial/ethnic differences in post-acute sequelae of SARS-CoV-2 in children and adolescents in the United States.

Racial/ethnic differences are associated with the symptoms and conditions of post-acute sequelae SARS-CoV-2 infection (PASC) in adults. These differences may exist among children and warrant further exploration. We conducted a retrospective cohort study with difference-in-differences analyzes to assess these differences in children and adolescents under the age of 21.