Effect of midazolam co-administered with oxycodone on ventilation: a randomised clinical trial in healthy volunteers.

Background: Benzodiazepines can exacerbate opioid-induced respiratory depression by furthering the decrease in central respiratory drive and causing loss of upper airway patency potentially leading to airway obstruction. This study aimed to determine if co-administration of benzodiazepines and opioids significantly decreases hypercapnic ventilation compared with opioids alone.

Methods: We conducted a randomised, double-blind, four-period crossover trial in 20 healthy participants to assess whether i.

Exploring Approaches to Mental Health Treatment and the Critical Role of Partnerships Among Hospital-Based Violence Intervention Programs.

Federal initiatives have invested considerable resources to end gun violence. Hospital-based violence intervention programs (HVIPs) are shown to reduce violent injury recidivism and address social needs of trauma-exposed clients. Mental health is a significant need among HVIP clients, yet little research on mental health and HVIPs exists.

Rehabilitation after surgical release of the stiff elbow: A literature review.

Background: Elbow stiffness poses a significant challenge for surgeons as well as physiotherapists during and after surgery. To date, there is no consensus regarding the subsequent rehabilitation after surgical release of the stiff elbow.

Objective: The aim is to evaluate the most important therapeutic strategies following open or arthroscopic release of the stiff elbow based on a comprehensive literature review, and to develop a consensus for or against specific therapeutic methods with the help of a survey among elbow experts of the D-A-CH Association for Shoulder and Elbow Surgery (DVSE).

Supporting Children's Mental Health Needs in Disasters.

Public health emergencies, including climate-related and manmade disasters such as active shooter incidents, occur regularly in the United States. A comprehensive approach is needed to ensure that children's mental health needs are adequately addressed following disasters. This article summarizes the latest evidence on how health systems can effectively address children's unique developmental, social, emotional, and behavioral needs in the context of disasters.

Untargeted metabolomics and lipidomics in COVID-19 patient plasma reveals disease severity biomarkers.

Introduction: Coronavirus disease 2019 (COVID-19) has widely varying clinical severity. Currently, no single marker or panel of markers is considered standard of care for prediction of COVID-19 disease progression. The goal of this study is to gain mechanistic insights at the molecular level and to discover predictive biomarkers of severity of infection and outcomes among COVID-19 patients.

RNA exon editing: Splicing the way to treat human diseases.

RNA exon editing is a therapeutic strategy for correcting disease-causing mutations by inducing -splicing between a synthetic RNA molecule and an endogenous pre-mRNA target, resulting in functionally restored mRNA and protein. This approach enables the replacement of exons at the kilobase scale, addresses multiple mutations with a single therapy, and maintains native gene expression without changes to DNA. For genes larger than 5 kb, RNA exon editors can be delivered in a single vector despite AAV capacity limitations because only mutated exons need to be replaced.

Intranasal Naloxone Repeat Dosing Strategies and Fentanyl Overdose: A Simulation-Based Randomized Clinical Trial.

Importance: Questions have emerged as to whether standard intranasal naloxone dosing recommendations (ie, 1 dose with readministration every 2-3 minutes if needed) are adequate in the era of illicitly manufactured fentanyl and its derivatives (hereinafter, fentanyl).

Objective: To compare naloxone plasma concentrations between different intranasal naloxone repeat dosing strategies and to estimate their effect on fentanyl overdose.

Design, Setting, And Participants: This unblinded crossover randomized clinical trial was conducted with healthy participants in a clinical pharmacology unit (Spaulding Clinical Research, West Bend, Wisconsin) in March 2021.

Remdesivir Discontinuation Decisions Based on Thresholds of Aminotransferase in an Observational Registry.

Background: Remdesivir is an antiviral approved by the US Food and Drug Administration (FDA) for treatment of coronavirus disease 2019 (COVID-19), and aminotransferase elevation is commonly reported. Thresholds to be considered for discontinuation due to alanine aminotransferase (ALT) elevation differ between the FDA and European Medicines Agency (EMA). The primary objective was to describe aminotransferase thresholds being used in real-world practice for discontinuation of remdesivir in patients with COVID-19, and compare them with labeled recommendations.

Changes in Vertebral Bone Density and Paraspinal Muscle Morphology Following Spaceflight and 1 Year Readaptation on Earth.

Astronauts have an increased risk of back pain and disc herniation upon returning to Earth. Thus, it is imperative to understand the effects of spaceflight and readaptation to gravity on the musculoskeletal tissues of the spine. Here we investigated whether ~6 months of spaceflight led to regional differences in bone loss within the vertebral body.

Intraoperative visualization of the posterolateral ulnohumeral joint space is reliable to indicate overlengthening in radial head arthroplasty.

Introduction: Avoiding overlengthening in radial head arthroplasty (RHA) is essential for the prognosis of the elbow joint. An overlengthening from 2 mm is visible due to widening of the anterolateral ulnohumeral joint space but intraoperatively, this particular joint space is difficult to visualize. The commonly used Kocher approach allows visualization of the posterolateral joint space without additional instruments or further surgical release of the already unstable elbow.

Adverse Events in Pregnant Patients Treated with Coronavirus Disease 2019 Therapeutics.

Background: Pregnant patients are at high risk of maternal and fetal complications from Coronavirus Disease 2019 (COVID-19) infections. The COVID-19 pandemic prompted a surge in the development and repurposing of therapies for the SARS-CoV-2 virus. Evidence is sparse on the efficacy and safety of these therapies in pregnant patients.

Rewiring Drug Research and Development through Human Data-Driven Discovery (HD).

In an era of unparalleled technical advancement, the pharmaceutical industry is struggling to transform data into increased research and development efficiency, and, as a corollary, new drugs for patients. Here, we briefly review some of the commonly discussed issues around this counterintuitive innovation crisis. Looking at both industry- and science-related factors, we posit that traditional preclinical research is front-loading the development pipeline with data and drug candidates that are unlikely to succeed in patients.

Profiles of Early Childhood Adversity in an Urban Pediatric Clinic: Implications for Pediatric Primary Care.

Pediatricians are well-positioned to screen for early childhood adversities, but effective responses to positive screens require an understanding of which adversities typically co-occur, and to what extent they are associated with other risk or protective factors. Among children seen at an urban academic pediatric practice, this study aimed to (1) examine the prevalence of different types of early adversity and protective experiences reported by primary caregivers, and (2) define latent classes of co-occurring adversities. Of 1434 children whose parents completed the Safe Environment for Every Kid (SEEK) at well-child visits during November 2019-January 2021, three classes of adverse experiences emerged, including those reporting low adversity (L; 73%), caregiver stress (CS; 17%), and both caregiver stress and depression (CSD; 10%).

Psychosocial Treatment of an Adolescent in a Hospital-Based Violence Intervention Program.

Interpersonal violence is the leading cause of death in adolescents. Hospital-based violence intervention programs (HVIPs) address the emotional and behavioral sequelae of assault and homicide. Few studies have been published on pediatric HVIPs, and no study offers a conceptualization model for treatment approaches.

A Scoping Review of Trauma-Informed Pediatric Interventions in Response to Natural and Biologic Disasters.

A scoping review was performed of trauma-informed psychological interventions to treat anxiety, depression, and posttraumatic stress symptoms in youth in response to natural/biologic disasters. The specific aims were to identify psychosocial interventions used in response to natural/biologic disasters, report the interventions' effectiveness, describe limitations, and provide treatment recommendations and future directions. Of the 45 studies extracted, 28 were on natural disasters and 17 on biologic disasters with the majority related to the COVID-19 pandemic.

[Epicondylosis : Open surgical procedure-when and how for lateral and medial epicondylitis?].

Background: Epicondylosis of the elbow are common pathologies, with a higher incidence for radial epicondylosis. Approximately 90% are self-limiting under conservative treatment.

Treatment: Multiple surgical procedures exist for the treatment of refractory cases.

Identification of Bradycardia Following Remdesivir Administration Through the US Food and Drug Administration American College of Medical Toxicology COVID-19 Toxic Pharmacovigilance Project.

Importance: The rapid spread and mortality associated with COVID-19 emphasized a need for surveillance system development to identify adverse events (AEs) to emerging therapeutics. Bradycardia is a remdesivir infusion-associated AE listed in the US Food and Drug Administration-approved prescribing information.

Objective: To evaluate the magnitude and duration of bradycardic events following remdesivir administration.

New science, drug regulation, and emergent public health issues: The work of FDA's division of applied regulatory science.

The U.S. Food and Drug Administration (FDA) Division of Applied Regulatory Science (DARS) moves new science into the drug review process and addresses emergent regulatory and public health questions for the Agency.

Improving Surveillance and Epidemic Response in Ohio Childcare Settings.

At the start of the Coronavirus Disease of 2019 (COVID-19) pandemic, the risk of cases in childcare programs was unknown. Thus, a rapid-response research approach was launched in Ohio childcare settings. Passive surveillance data from a state-operated incident reporting system were evaluated to estimate the number of COVID-19 cases from 15 August 2020 to 1 January 2021.

Effect of Paroxetine or Quetiapine Combined With Oxycodone vs Oxycodone Alone on Ventilation During Hypercapnia: A Randomized Clinical Trial.

Importance: Opioids can cause severe respiratory depression by suppressing feedback mechanisms that increase ventilation in response to hypercapnia. Following the addition of boxed warnings to benzodiazepine and opioid products about increased respiratory depression risk with simultaneous use, the US Food and Drug Administration evaluated whether other drugs that might be used in place of benzodiazepines may cause similar effects.

Objective: To study whether combining paroxetine or quetiapine with oxycodone, compared with oxycodone alone, decreases the ventilatory response to hypercapnia.

[Coronoid reconstruction with autologous iliac crest bone graft in chronic elbow instability through a medial approach].

Objective: Neutralizing a posteromedial rotatory instability (PMRI) caused by coronoid deficiency by restoration of the humeroulnar joint surface with an autologous iliac crest bone graft.

Indications: Surgery is indicated in patients with chronic deficiency of the anteromedial facet of the coronoid with subsequent PMRI.

Contraindications: Coronoid reconstruction is not recommended in patients with advanced osteoarthritis of the elbow caused by subluxation of the humeroulnar joint.

Introduction to the Special Issue on Adverse Childhood Experiences (ACEs): Prevention, Intervention, and Access to Care.

Exposure to adverse childhood experiences (ACEs) is an international public health problem [...