Browsing by Author "Bhutta, Adnan"

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    Development of a primate model to evaluate the effects of ketamine and surgical stress on the neonatal brain
    (Sage, 2023) Wang, Cheng; Bhutta, Adnan; Zhang, Xuan; Liu, Fang; Liu, Shuliang; Latham, Leah E.; Talpos, John C.; Patterson, Tucker A.; Slikker, William, Jr.; Pediatrics, School of Medicine
    With advances in pediatric and obstetric surgery, pediatric patients are subject to complex procedures under general anesthesia. The effects of anesthetic exposure on the developing brain may be confounded by several factors including pre-existing disorders and surgery-induced stress. Ketamine, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, is routinely used as a pediatric general anesthetic. However, controversy remains about whether ketamine exposure may be neuroprotective or induce neuronal degeneration in the developing brain. Here, we report the effects of ketamine exposure on the neonatal nonhuman primate brain under surgical stress. Eight neonatal rhesus monkeys (postnatal days 5-7) were randomly assigned to each of two groups: Group A (n = 4) received 2 mg/kg ketamine via intravenous bolus prior to surgery and a 0.5 mg/kg/h ketamine infusion during surgery in the presence of a standardized pediatric anesthetic regimen; Group B (n = 4) received volumes of normal saline equivalent to those of ketamine given to Group A animals prior to and during surgery, also in the presence of a standardized pediatric anesthetic regimen. Under anesthesia, the surgery consisted of a thoracotomy followed by closing the pleural space and tissue in layers using standard surgical techniques. Vital signs were monitored to be within normal ranges throughout anesthesia. Elevated levels of cytokines interleukin (IL)-8, IL-15, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-1β at 6 and 24 h after surgery were detected in ketamine-exposed animals. Fluoro-Jade C staining revealed significantly higher neuronal degeneration in the frontal cortex of ketamine-exposed animals, compared with control animals. Intravenous ketamine administration prior to and throughout surgery in a clinically relevant neonatal primate model appears to elevate cytokine levels and increase neuronal degeneration. Consistent with previous data on the effects of ketamine on the developing brain, the results from the current randomized controlled study in neonatal monkeys undergoing simulated surgery show that ketamine does not provide neuroprotective or anti-inflammatory effects.
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    Etiology of hospital mortality in children living in low- and middle-income countries: a systematic review and meta-analysis
    (Frontiers Media, 2024-06-07) Kortz, Teresa B.; Mediratta, Rishi P.; Smith, Audrey M.; Nielsen, Katie R.; Agulnik, Asya; Gordon Rivera, Stephanie; Reeves, Hailey; O'Brien, Nicole F.; Hau Lee, Jan; Abbas, Qalab; Attebery, Jonah E.; Bacha, Tigist; Bhutta, Emaan G.; Biewen, Carter J.; Camacho-Cruz, Jhon; Coronado Muñoz, Alvaro; deAlmeida, Mary L.; Owusu, Larko Domeryo; Fonseca, Yudy; Hooli, Shubhada; Wynkoop, Hunter; Leimanis-Laurens, Mara; Mally, Deogratius Nicholaus; McCarthy, Amanda M.; Mutekanga, Andrew; Pineda, Carol; Remy, Kenneth E.; Sanders, Sara C.; Tabor, Erica; Teixeira Rodrigues, Adriana; Yuee Wang, Justin Qi; Kissoon, Niranjan; Takwoingi, Yemisi; Wiens, Matthew O.; Bhutta, Adnan; Pediatrics, School of Medicine
    In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, and total admissions. We excluded studies with data before 2,000 or without a full text. Two authors independently screened and extracted data. We performed methodological assessment using domains adapted from the Quality in Prognosis Studies tool. Data were pooled using random-effects models where possible. We reported prevalence as a proportion of cause of death or admission per 1,000 admissions with 95% confidence intervals (95% CI). Our search identified 29,637 texts. After duplicate removal and screening, we analyzed 253 studies representing 21.8 million pediatric hospitalizations in 59 LMICs. All-cause pediatric hospital mortality was 4.1% [95% CI 3.4%–4.7%]. The most common causes of mortality (deaths/1,000 admissions) were infectious [12 (95% CI 9–14)]; respiratory [9 (95% CI 5–13)]; and gastrointestinal [9 (95% CI 6–11)]. Common causes of admission (cases/1,000 admissions) were respiratory [255 (95% CI 231–280)]; infectious [214 (95% CI 193–234)]; and gastrointestinal [166 (95% CI 143–190)]. We observed regional variation in estimates. Pediatric hospital mortality remains high in LMICs. Global child health efforts must include measures to reduce hospital mortality including basic emergency and critical care services tailored to the local disease burden. Resources are urgently needed to promote equity in child health research, support researchers, and collect high-quality data in LMICs to further guide priority setting and resource allocation.
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    Prevalence of Pulmonary Embolism in COVID-19 Positive Critically Ill Children
    (Wolters Kluwer, 2025-01-15) Fonseca, Yudy; Davies, Alise; Jarrin, Stephanie; Simon, Liliana; Foster, Cortney; Kai, Sun; Bhutta, Adnan; Pediatrics, School of Medicine
    Objectives: To investigate the prevalence of pulmonary embolism (PE) in children admitted to critical care diagnosed with COVID-19 infection. Design: Retrospective database study. Setting: Data reported to the Virtual Pediatric Systems, 2018-2021. Patients: Patients 28 days to younger than 18 years old, admitted to a PICU with either PE or COVID-19 diagnoses. Interventions: None. Measurements and main results: Among the PE-positive subgroups, from January 2020 to December 2021, 78 patients (14%) had an acute COVID-19 infection. The prevalence of PE pre-pandemic period (2018-2019) was 0.19% and for pandemic period (2020-2021) was 0.26% (p < 0.001). During the pandemic period, the prevalence of PE for COVID-negative patients was 0.21% and for COVID-positive patients was 1.01% (p < 0.001). The result shows that the chance to develop PE for COVID-positive patients is 4.8 times that for COVID-negative patients during the pandemic. In the subgroup of the PE-positive patients, 55.1% were Black or African American in the COVID-positive group and 19% in the COVID-negative group (p < 0.001). A multivariable logistic regression showed that race was an independent risk factor for COVID in PE-positive patients. Conclusions: Our study demonstrates a significant increase in the prevalence of PE among pediatric patients admitted to PICUs during the COVID-19 pandemic compared with pre-pandemic. Our study indicates that COVID-positive patients are 4.8 times more likely to develop PE than COVID-negative patients. Additionally, the study highlights substantial racial disparities in the prevalence of PE, with Black or African American patients being disproportionately affected.
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    Verbal Autopsy to Assess Postdischarge Mortality in Children With Suspected Sepsis in Uganda
    (American Academy of Pediatrics, 2023) Knappett, Martina; Hooft, Anneka; Maqsood, Muhammad Bilal; Lavoie, Pascal M.; Kortz, Teresa; Mehta, Sonia; Duby, Jessica; Akech, Samuel; Maina, Michuki; Carter, Rebecca; Popescu, Constantin R.; Daftary, Rajesh; Mugisha, Nathan Kenya; Mwesigwa, Douglas; Kabakyenga, Jerome; Kumbakumba, Elias; Ansermino, J. Mark; Kissoon, Niranjan; Mutekanga, Andrew; Hau, Duncan; Moschovis, Peter; Kangwa, Mukuka; Chen, Carol; Firnberg, Maytal; Glomb, Nicolaus; Argent, Andrew; Reid, Stephen J.; Bhutta, Adnan; Wiens, Matthew O.; Pediatrics, School of Medicine
    Background: Reducing child mortality in low-income countries is constrained by a lack of vital statistics. In the absence of such data, verbal autopsies provide an acceptable method to determining attributable causes of death. The objective was to assess potential causes of pediatric postdischarge mortality in children younger than age 5 years (under-5) originally admitted for suspected sepsis using verbal autopsies. Methods: Secondary analysis of verbal autopsy data from children admitted to 6 hospitals across Uganda from July 2017 to March 2020. Structured verbal autopsy interviews were conducted for all deaths within 6 months after discharge. Two physicians independently classified a primary cause of death, up to 4 alternative causes, and up to 5 contributing conditions using the Start-Up Mortality List, with discordance resolved by consensus. Results: Verbal autopsies were completed for 361 (98.6%) of the 366 (5.9%) children who died among 6191 discharges (median admission age: 5.4 months [interquartile range, 1.8-16.7]; median time to mortality: 28 days [interquartile range, 9-74]). Most deaths (62.3%) occurred in the community. Leading primary causes of death, assigned in 356 (98.6%) of cases, were pneumonia (26.2%), sepsis (22.1%), malaria (8.5%), and diarrhea (7.9%). Common contributors to death were malnutrition (50.5%) and anemia (25.7%). Reviewers were less confident in their causes of death for neonates than older children (P < .05). Conclusions: Postdischarge mortality frequently occurred in the community in children admitted for suspected sepsis in Uganda. Analyses of the probable causes for these deaths using verbal autopsies suggest potential areas for interventions, focused on early detection of infections, as well as prevention and treatment of underlying contributors such as malnutrition and anemia.