Updated analysis of the pharmacogenomics of pediatric bronchodilator response.

This short communication serves as an update to previously published pilot study results on bronchodilator response (BDR) in children with asthma. We expanded our cohort from 54 to 165 pediatric patients seeking emergency department care for an asthma exacerbation. We obtained measured BDR before and after albuterol administration using the Pediatric Asthma Severity Score and collected genomic DNA.

Who gets the bed: Factors influencing the intensive care exit block: A qualitative study.

Background: Patient flow problems, including discharge delay and after-hours discharge, have been a consistently major issue, especially for intensive care units (ICUs). Evidence suggests that discharge delay and after-hours discharge are associated with increased ICU and hospital length of stay, leading to worsened patient outcomes and increased healthcare costs. They can also increase ICU readmission and post-ICU mortality.

Contextual Factors Influencing Intensive Care Patients' Discharge Processes: A Multicentre Prospective Observational Study.

Aims: To compare contextual factors influencing discharge practices in three intensive care units (ICUs).

Design: A prospective observational study.

Methods: Data were collected using a discharge process report form (DPRF) between May and September 2023.

Combining Federated Machine Learning and Qualitative Methods to Investigate Novel Pediatric Asthma Subtypes: Protocol for a Mixed Methods Study.

Background: Pediatric asthma is a heterogeneous disease; however, current characterizations of its subtypes are limited. Machine learning (ML) methods are well-suited for identifying subtypes. In particular, deep neural networks can learn patient representations by leveraging longitudinal information captured in electronic health records (EHRs) while considering future outcomes.

Development of a Computable Phenotype for Prehospital Pediatric Asthma Encounters.

Introduction: Asthma exacerbations are a common cause of pediatric Emergency Medical Services (EMS) encounters. Accordingly, prehospital management of pediatric asthma exacerbations has been designated an EMS research priority. However, accurate identification of pediatric asthma exacerbations from the prehospital record is nuanced and difficult due to the heterogeneity of asthma symptoms, especially in children.

Interventions to improve patient admission and discharge practices in adult intensive care units: A systematic review.

Objectives: To identify and synthesise interventions and implementation strategies to optimise patient flow, addressing admission delays, discharge delays, and after-hours discharges in adult intensive care units.

Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Five electronic databases, including CINAHL, PubMed, Emcare, Scopus, and the Cochrane Library, were searched from 2007 to 2023 to identify articles describing interventions to enhance patient flow practices in adult intensive care units.

A pilot study to identify pharmacogenomic and clinical risk factors associated with opioid related falls and adverse effects in older adults.

Given the high prevalence of pain in older adults and current trends in opioid prescribing, inclusion of genetic information in risk prediction tools may improve opioid risk assessment. Our objectives were to (1) determine the feasibility of recruiting socioeconomically disadvantaged and racially diverse middle aged and older adult populations for a study seeking to identify risk factors for opioid-related falls and other serious adverse effects and (2) explore potential associations between the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD) risk class and other patient factors with falls and serious opioid adverse effects. This was an observational study of 44 participants discharged home from the emergency department with an opioid prescription for acute pain and followed for 30 days.

Establishing critical care nursing research priorities for three Australian regional public hospitals: A mixed method priority setting study.

Objective: To determine key priorities for critical care nursing research in three Australian regional public hospitals, representing the shared priorities of healthcare professionals and patient representatives.

Methods: A three phase priority setting study, including consensus methods (nominal group), survey, qualitative interviews and focus groups were conducted between May 2021 and March 2022. Healthcare professionals and patient representatives from critical care units in regional public hospitals in Australia participated.

Emergency Medical Services Leadership Perspectives on Implementation of Evidence-Based Guidelines: A Qualitative Study.

Prehospital evidence-based guidelines (EBGs) are developed to optimize clinical outcomes for emergency medical services (EMS) patients. However, widespread implementation of EBGs is often inconsistent. Therefore, this study aimed to assess the baseline knowledge and practices of EMS leaders related to EBG implementation.

Implementing Oral Systemic Corticosteroids for Pediatric Asthma into EMS Treatment Guidelines: A Qualitative Study.

Respiratory distress accounts for approximately 14% of all pediatric emergency medical services (EMS) encounters, with asthma being the most common diagnosis. In the emergency department (ED), early administration of systemic corticosteroids decreases hospital admission and speeds resolution of symptoms. For children treated by EMS, there is an opportunity for earlier corticosteroid administration.

Clinical Trial Participation: A Qualitative Study of Adolescents and Younger Adults Recently Diagnosed with Cancer.

Although participation of adolescents and young adults (AYAs) in cancer clinical trials (CCTs, i.e., cancer-directed treatment studies) is low, their decision-making perspectives are not well understood, especially following recent diagnosis.

Validating the HELP Survey to Understand Health Disparity Influence on Chronic Pain.

Background: Socioeconomic deprivation is shown to be linked to chronic lower back pain. However, a comprehensive approach to identify key components contributing to pain outcomes using a biopsychosocial model incorporating social determinants of health is needed to develop and tailor successful strategies for mitigating chronic pain development and persistence. We aimed to develop and validate an instrument (the HELP survey) to assess themes characterized by a combination of social determinants of health and the biopsychosocial model in an underserved population.

A national survey of pediatric emergency medicine physicians on improving education in child maltreatment recognition and reporting child abuse & neglect.

Background: Child maltreatment is an important public health problem with serious consequences. Even in the face of increased research and enhanced public awareness over the last decade, the rate of child fatalities due to reported child maltreatment has increased.

Objective: This study describes pediatric emergency medicine (PEM) physicians' knowledge, training, confidence, and barriers in recognition and reporting suspected child maltreatment.

Early administration of steroids in the ambulance setting: Protocol for a type I hybrid effectiveness-implementation trial with a stepped wedge design.

Background: Pediatric asthma exacerbations are a frequent reason for emergency care. Early administration of oral systemic corticosteroids (OCS) in the emergency department (ED) decreases hospitalization rates and ED length-of-stay (LOS). However, it is unknown whether even earlier OCS administration by emergency medical services (EMS) in the prehospital setting further improves outcomes.

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.

Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.

Design, Setting, And Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin.

Synthesis of stable-isotope-labeled N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide and N-(3-dimethylaminopropyl)-N'-ethylurea.

N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) is a carbodiimide coupling reagent commonly used for the preparation of amides from carboxylic acids and amines. Because of initial concerns regarding the genotoxicity of EDC and its use in GMP syntheses at Bristol Myers Squibb, the quantitation of residual EDC and its by-product N-(3-dimethylaminopropyl)-N'-ethylurea (EDU) by liquid chromatography-mass spectrometry (LCMS) impurity analysis was required. These analyses required the use of stable-isotope-labeled EDC and EDU to serve as internal standards.

Total Chemical Synthesis of Human Thyroid-Stimulating Hormone (hTSH) -Subunit: Application of Arginine-tagged Acetamidomethyl (Acm) Protecting Groups.

The β-subunit of human thyroid stimulating hormone (hTSH) has been synthesized as a single glycoform bearing a chitobiose disaccharide at the native glycosylation site. Key to the successful completion of this synthesis was the introduction of an arginine-tagged acetamidomethyl group, which served to greatly facilitate handling of a glycopeptide fragment with poor aqueous solubility. This general solution to the challenge of working with intractable peptides is expected to find wide use in protein synthesis.

Adnectin-drug conjugates for Glypican-3-specific delivery of a cytotoxic payload to tumors.

Tumor-specific delivery of cytotoxic agents remains a challenge in cancer therapy. Antibody-drug conjugates (ADC) deliver their payloads to tumor cells that overexpress specific tumor-associated antigens-but the multi-day half-life of ADC leads to high exposure even of normal, antigen-free, tissues and thus contributes to dose-limiting toxicity. Here, we present Adnectin-drug conjugates, an alternative platform for tumor-specific delivery of cytotoxic payloads.

Synthesis of unlabelled and stable-isotope-labelled glucuronide metabolites of dapagliflozin and synthesis of stable-isotope-labelled dapagliflozin.

Two regioisomeric glucuronide metabolites of dapagliflozin (BMS-512148) were synthesized and used to elucidate the structures of dapagliflozin metabolites observed in human urine samples. The structures of the synthetic metabolites were assigned by heteronuclear multiple-bond correlation, ROESY, and total correlation spectroscopy experiments. Analogues of these metabolites containing carbon-13 as a stable label were also prepared for use as internal standards for the analysis of urine samples obtained from patients participating in clinical studies.

Characterization and quantification of histidine degradation in therapeutic protein formulations by size exclusion-hydrophilic interaction two dimensional-liquid chromatography with stable-isotope labeling mass spectrometry.

Two dimensional liquid chromatography (2D-LC) coupling size exclusion (SEC) and hydrophilic interaction chromatography (HILIC) is demonstrated as a useful tool to study polar excipients, such as histidine and its degradant, in protein formulation samples. The SEC-HILIC setup successfully removed interferences from complex sample matrices and enabled accurate mass measurement of the histidine degradation product, which was then determined to be trans-urocanic acid. Because the SEC effluent is a strong solvent for the second dimension HILIC, experimental parameters needed to be carefully chosen, i.

Synthesis of 2-(14)C-iminothiolane and 2-(13)C,(15)N-iminothiolane (Traut's reagent).

2-Iminothiolane has found utility in the growing area of antibody-drug conjugates by serving as a lysine-thiolating agent and the junction between the antibody and the cytotoxic payload during random conjugation of a monoclonal antibody. 2-(14)C-Iminothiolane was prepared from commercially available [(14)C]KCN using a four-step sequence in an overall 10% radiochemical yield. Stable-labeled 2-(13)C,(15)N-iminothiolane was also prepared from [(13)C(15)N]KCN in a similar manner.

Total synthesis of glycosylated proteins.

Glycoproteins are an important class of naturally occurring biomolecules which play a pivotal role in many biological processes. They are biosynthesized as complex mixtures of glycoforms through post-translational protein glycosylation. This fact, together with the challenges associated with producing them in homogeneous form, has hampered detailed structure-function studies of glycoproteins as well as their full exploitation as potential therapeutic agents.

Progress toward the total synthesis of N-methylwelwitindolinone B isothiocyanate.

Progress toward the welwitindolinone alkaloid N-methylwelwitindolinone B isothiocyanate is reported. A key reaction to synthesize the [4.3.