Browsing by Author "Bhutta, Adnan T."

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    A research definition and framework for acute paediatric critical illness across resource-variable settings: a modified Delphi consensus
    (Elsevier, 2024) Arias, Anita V.; Lintner-Rivera, Michael; Shafi, Nadeem I.; Abbas, Qalab; Abdelhafeez, Abdelhafeez H.; Ali, Muhammad; Ammar, Halaashuor; Anwar, Ali I.; Appiah, John Adabie; Attebery, Jonah E.; Diaz Villalobos, Willmer E.; Ferreira, Daiane; González-Dambrauskas, Sebastián; Habib, Muhammad Irfan; Lee, Jan Hau; Kissoon, Niranjan; Tekleab, Atnafu M.; Molyneux, Elizabeth M.; Morrow, Brenda M.; Nadkarni, Vinay M.; Rivera, Jocelyn; Silvers, Rebecca; Steere, Mardi; Tatay, Daniel; Bhutta, Adnan T.; Kortz, Teresa B.; Agulnik, Asya; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network on behalf of the PALISI Global Health Subgroup; Pediatrics, School of Medicine
    The true global burden of paediatric critical illness remains unknown. Studies on children with life-threatening conditions are hindered by the absence of a common definition for acute paediatric critical illness (DEFCRIT) that outlines components and attributes of critical illness and does not depend on local capacity to provide critical care. We present an evidence-informed consensus definition and framework for acute paediatric critical illness. DEFCRIT was developed following a scoping review of 29 studies and key concepts identified by an interdisciplinary, international core expert panel (n=24). A modified Delphi process was then done with a panel of multidisciplinary health-care global experts (n=109) until consensus was reached on eight essential attributes and 28 statements as the basis of DEFCRIT. Consensus was reached in two Delphi rounds with an expert retention rate of 89%. The final consensus definition for acute paediatric critical illness is: an infant, child, or adolescent with an illness, injury, or post-operative state that increases the risk for or results in acute physiological instability (abnormal physiological parameters or vital organ dysfunction or failure) or a clinical support requirement (such as frequent or continuous monitoring or time-sensitive interventions) to prevent further deterioration or death. The proposed definition and framework provide the conceptual clarity needed for a unified approach for global research across resource-variable settings. Future work will centre on validating DEFCRIT and determining high priority measures and guidelines for data collection and analysis that will promote its use in research.
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    Challenges in institutional ethical review process and approval for international multicenter clinical studies in lower and middle-income countries: the case of PARITY study
    (Frontiers Media, 2024-11-05) Lopez-Baron, Eliana; Abbas, Qalab; Caporal, Paula; Agulnik, Asya; Attebery, Jonah E.; Holloway, Adrian; Kissoon, Niranjan Tex; Mulgado-Aguas, Celia Isabel; Amegan-Aho, Kokou; Majdalani, Marianne; Ocampo, Carmen; Pascal, Havugarurema; Miller, Erika; Kanyamuhunga, Aimable; Tekleab, Atnafu Mekonnen; Bacha, Tigist; González-Dambrauskas, Sebastian; Bhutta, Adnan T.; Kortz, Teresa B.; Murthy, Srinivas; Remy, Kenneth E.; Global Health Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network; Pediatrics, School of Medicine
    Background: One of the greatest challenges to conducting multicenter research studies in low and middle-income countries (LMICs) is the heterogeneity in regulatory processes across sites. Previous studies have reported variations in requirements with a lack of standardization in the Institutional Review Board (IRB) processes between centers, imposing barriers for approval, participation, and development of multicenter research. Objectives: To describe the regulatory process, variability and challenges faced by pediatric researchers in LMICs during the IRB process of an international multicenter observational point prevalence study (Global PARITY). Design: A 16-question multiple-choice online survey was sent to site principal investigators (PIs) at PARITY study participating centers to explore characteristics of the IRB process, costs, and barriers to research approval. A shorter survey was employed for sites that expressed interest in participating in Global PARITY and started the approval process, but ultimately did not participate in data collection (non-participating sites) to assess IRB characteristics. Results: Of the 91 sites that sought IRB approval, 46 were successful in obtaining approval and finishing the data collection process. The survey was completed by 46 (100%) participating centers and 21 (47%) non-participating centers. There was a significant difference between participating and non-participating sites in IRB approval of a waiver consent and in the requirement for a legal review of the protocol. The greatest challenge to research identified by non-participating sites was a lack of research time and the lack of institutional support. Conclusions: Global collaborative research is crucial to increase our understanding of pediatric critical care conditions in hospitals of all resource-levels and IRBs are required to ensure that this research complies with ethical standards. Critical barriers restrict research activities in some resource limiting countries. Increasing the efficiency and accessibility of local IRB review could greatly impact participation of resource limited sites and enrollment of vulnerable populations.
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    Evaluation of Vancomycin Dose Needed to Achieve 24-Hour Area Under the Concentration-Time Curve to Minimum Inhibitory Concentration Ratio Greater Than or Equal to 400 Using Pharmacometric Approaches in Pediatric Intensive Care Patients
    (Wolters Kluwer, 2024-10-01) Jung, Dawoon; Kishk, Omayma A.; Bhutta, Adnan T.; Cummings, Ginny E.; El Sahly, Hana M.; Virk, Manpreet K.; Moffett, Brady S.; Morris Daniel, Jennifer L.; Watanabe, Amy; Fishbane, Nicholas; Kotloff, Karen L.; Gu, Kenan; Ghazaryan, Varduhi; Gobburu, Jogarao V. S.; Akcan-Arikan, Ayse; Campbell, James D.; Pediatrics, School of Medicine
    Objectives: To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400. Design: Prospective population pharmacokinetic study of vancomycin. Setting: Critically ill patients in quaternary care PICUs. Patients: Children 90 days old or older to younger than 18 years who received IV vancomycin treatment, irrespective of the indication for use, in the ICUs at the University of Maryland Children's Hospital and Texas Children's Hospital were enrolled. Interventions: Vancomycin was prescribed at doses and intervals chosen by the treating clinicians. Measurements and main results: A median of four serum levels of vancomycin per patient were collected along with other variables for up to 7 days following the first administration. These data were used to characterize vancomycin pharmacokinetics and evaluate the factors affecting the variability in achieving AUC24/MIC ratio greater than or equal to 400 in PICU patients who are not on extracorporeal therapy. A total of 302 children with a median age of 6.0 years were enrolled. A two-compartment model described the pharmacokinetics of vancomycin with the clearance of 2.76 L/hr for a typical patient weighing 20 kg. The glomerular filtration rate estimated using either the bedside Schwartz equation or the chronic kidney disease in children equation was the only statistically significant predictor of clearance among the variables evaluated, exhibiting equal predictive performance. The trough levels achieving AUC24/MIC = 400 were 5.6-10.0 μg/mL when MIC = 1 μg/mL. The target of AUC24/MIC greater than or equal to 400 was achieved in 60.4% and 36.5% with the typical dosing regimens of 15 mg/kg every 6 and 8 hours (q6h and q8h), respectively. Conclusions: The pharmacokinetics of vancomycin in critically ill children were dependent on the estimated glomerular filtration rate only. Trough concentrations accurately predict AUC24. Typical pediatric vancomycin dosing regimens of 15 mg/kg q6h and q8h will often lead to AUC24/MIC under 400.