Publications by authors named "Markham J"

Administrative databases are powerful tools for pediatric research but lack patient-level microbiology results. This study aimed to determine the accuracy of pathogen discharge diagnosis codes for children hospitalized with acute hematogenous musculoskeletal infections (MSKIs). Medical records for 244 children hospitalized with acute hematogenous MSKIs were manually reviewed to determine which bacterial pathogen, if any, was identified for each MSKI based on microbiology results obtained during the hospitalization.

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Background And Objective: Treatment of postoperative pain for children with severe neurologic impairment (SNI) is challenging. We describe the type, number of classes, and duration of postoperative pain medications for procedures common among children with SNI, as well as the variability across children's hospitals in pain management with an emphasis on opioid prescribing.

Methods: This retrospective cohort study included children with SNI ages 0-21 years old who underwent common procedures between January 1, 2019 and December 31, 2019 within 49 children's hospitals in the Pediatric Health Information System.

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Background And Objective: Few studies have explored the relationship between social drivers of health and pediatric low-value care (LVC). We assessed the relationship between Childhood Opportunity Index (COI) 2.0 and LVC in children's hospitals.

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Background: Despite nationally endorsed treatment guidelines and stewardship programs, variation and deviation from evidence-based antibiotic prescribing occur, contributing to inappropriate use and medication-related adverse events. Measures of antibiotic prescribing variability can aid in quantifying this problem but are not adequate.

Objective: The objective of this study is to develop a standardized metric to quantify antibiotic prescribing variability (diversity) within and across children's hospitals, and to examine its association with outcomes.

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Synthetic cannabinoid receptor agonists (SCRAs) comprise the second largest class of new psychoactive substances (NPS), and typically α-amino acid moieties are incorporated as part of their design. Limited investigation has been performed into elucidating structure-activity relationships around commonly used α-amino acid-derived head groups, mainly with valine and -leucine-derived compounds previously described. As such, proactive synthesis, characterisation and pharmacological evaluation were performed to explore structure-activity relationships of 15 α-amino acid derivatives, with both the natural isomers and their enantiomers at CB and CB investigated using a fluorescence-based membrane potential assay.

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Synthetic cannabinoid receptor agonists (SCRAs) are a growing class of new psychoactive substances (NPS) commonly derived from an -alkylated indole, indazole, or 7-azaindole scaffold. Diversification of this core (at the 3-position) with amide-linked pendant amino acid groups and modular -alkylation (of the indole/indazole/7-azaindole core) ensures that novel SCRAs continue to enter the illicit drug market rapidly. In response to the large number of SCRAs that have been detected, pharmacological evaluation of this NPS class has become increasingly common.

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Article Synopsis
  • The study evaluates how many hospitalized children with UTIs receive narrow-spectrum versus broad-spectrum antibiotics and their outcomes.
  • About 5% of children were given narrow-spectrum antibiotics, with variations among hospitals, despite high susceptibility of E. coli in many facilities.
  • Patients treated with narrow-spectrum antibiotics had shorter hospital stays and lower costs, but no difference in emergency department revisits or readmissions was observed.
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Background: Nearly 25% of antibiotics prescribed to children are inappropriate or unnecessary, subjecting patients to avoidable adverse medication effects and cost.

Methods: We conducted a quality improvement initiative across 118 hospitals participating in the American Academy of Pediatrics Value in Inpatient Pediatrics Network 2020 to 2022. We aimed to increase the proportion of children receiving appropriate: (1) empirical, (2) definitive, and (3) duration of antibiotic therapy for community-acquired pneumonia, skin and soft tissue infections, and urinary tract infections to ≥85% by Jan 1, 2022.

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Background: Research into low-value routine testing at children's hospitals has not consistently evaluated changing patterns of testing over time.

Objectives: To identify changes in routine laboratory testing rates at children's hospitals over ten years and the association with patient outcomes.

Design, Settings, And Participants: We performed a multi-center, retrospective cohort study of children aged 0-18 hospitalized with common, lower-severity diagnoses at 28 children's hospitals in the Pediatric Health Information Systems database.

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ADB-HEXINACA has been recently reported as a synthetic cannabinoid receptor agonist (SCRA), one of the largest classes of new psychoactive substances (NPSs). This compound marks the entry of the -hexyl tail group into the SCRA landscape, which has continued in the market with recent, newly detected SCRAs. As such, a proactive characterization campaign was undertaken, including the synthesis, characterization, and pharmacological evaluation of ADB-HEXINACA and a library of 41 closely related analogues.

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Background: Phlebotomy for hospitalized children has consequences (e.g., pain, iatrogenic anemia), and unnecessary testing is a modifiable source of waste in healthcare.

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Article Synopsis
  • Homogenous catalysis is important for producing bulk and fine chemicals, with phosphine ligands like tricyclohexylphosphine (CYTOP® 366) playing a vital role in this process.
  • In designing the synthesis of these ligands, factors such as safety, yield, quality, cost, and available technologies must be weighed, especially for large-scale production.
  • The report details the chosen synthetic route for tricyclohexylphosphine, examining both the successes of this pathway and the failures of traditional hydrophosphination methods through computational calculations.
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Randomized controlled trials (RCTs) are the gold standard study design for clinical research, as prospective randomization, at least in theory, balances any differences that can exist between groups (including any differences not measured as part of the study) and isolates the studied treatment effect. Any remaining imbalances after randomization are attributable to chance. However, there are many barriers to conducting RCTs within pediatric populations, including lower disease prevalence, high costs, inadequate funding, and additional regulatory requirements.

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T-type Ca channels (Ca3) represent emerging therapeutic targets for a range of neurological disorders, including epilepsy and pain. To aid the development and optimisation of new therapeutics, there is a need to identify novel chemical entities which act at these ion channels. A number of synthetic cannabinoid receptor agonists (SCRAs) have been found to exhibit activity at T-type channels, suggesting that cannabinoids may provide convenient chemical scaffolds on which to design novel Ca3 inhibitors.

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Background And Objective: Children with gastrointestinal infections often require acute care.The objectives of this study were to describe variations in patterns of stool testing across children's hospitals and determine whether such variation was associated with utilization outcomes.

Design, Settings And Participants: We performed a multicenter, cross-sectional study using the Pediatric Health Information System (PHIS) database.

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Background: Targeted RNA sequencing (RNA-seq) from FFPE specimens is used clinically in cancer for its ability to estimate gene expression and to detect fusions. Using a cohort of NSCLC patients, we sought to determine whether targeted RNA-seq could be used to measure tumour mutational burden (TMB) and the expression of immune-cell-restricted genes from FFPE specimens and whether these could predict response to immune checkpoint blockade.

Methods: Using The Cancer Genome Atlas LUAD dataset, we developed a method for determining TMB from tumour-only RNA-seq and showed a correlation with DNA sequencing derived TMB calculated from tumour/normal sample pairs (Spearman correlation = 0.

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Synthetic cannabinoid receptor agonists (SCRAs) continue to make up a significant portion new psychoactive substances (NPS) detected and seized worldwide. Due to their often potent activation of central cannabinoid receptors , use of SCRAs can result in severe intoxication, in addition to other adverse health effects. Recent detections of AB-4CN-BUTICA, MMB-4CN-BUTINACA, MDMB-4F-BUTICA and MDMB-4F-BUTINACA mark a continuation in the appearance of SCRAs bearing novel tail substituents.

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Provider- and claims-focused administrative databases are powerful tools for conducting health services research, and these studies often have good generalizability owing to diversity of hospitals from which samples are derived. In this research methods article, we describe administrative data and how available provider- and claims-focused administrative databases can be used to conduct health services research. We describe common observational study designs using administrative data and provide real-world examples.

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Background: Current diagnostics do not permit reliable differentiation of bacterial from viral causes of lower respiratory tract infection (LRTI), which may lead to over-treatment with antibiotics for possible bacterial community-acquired pneumonia (CAP).

Objectives: We sought to describe variation in the diagnosis and treatment of bacterial CAP among children hospitalized with LRTIs and determine the association between CAP diagnosis and outcomes.

Design, Setting And Participants: This multicenter cross-sectional study included children hospitalized between 2017 and 2019 with LRTIs at 42 children's hospitals.

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The mining of the oil sands region of Canada's boreal forest creates disturbed land with elevated levels of salts. Understanding how native plants respond to salt stress is critical in reclaiming these lands. The native species, subsp.

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Objectives: Sources of variation within febrile infant management are incompletely described. In 2016, a national standardization quality improvement initiative, Reducing Excessive Variation in Infant Sepsis Evaluations (REVISE) was implemented. We sought to: (1) describe sociodemographic factors influencing laboratory obtainment and hospitalization among febrile infants and (2) examine the association of REVISE on any identified sources of practice variation.

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