Browsing by Author "Carroll, Ryan W."

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    Efficacy and safety of non-invasive ventilation in pediatric care in low-income and middle-income countries: a systematic review
    (medRxiv, 2021) Sessions, Kristen L.; Smith, Andrew G.; Holmberg, Peter J.; Mvalo, Tisuguane; Chisti, Mohammod J.; Carroll, Ryan W.; McCollum, Eric D.
    Lower respiratory tract infections (LRTIs) are a leading cause of under-5 mortality in low-income and middle-income countries (LMICs) and interventions to reduce mortality are needed. Non-invasive ventilation has been shown to reduce mortality for neonates; however, data for children >1 month of age in LMICs are lacking. The objective of this study was to systematically review the available literature to determine if non-invasive ventilation as the primary modality of respiratory support is efficacious and safe for the management of respiratory distress in non-neonatal pediatric patients in LMICs. Methods We systematically reviewed all studies assessing the endpoints of efficacy, effectiveness, and safety of non-invasive ventilation for pediatric LRTIs in LMICs. A comprehensive search of Medline, Embase, LILACS, Web of Science, and Scopus was performed on April 7, 2020. Included studies assessed the safety, efficacy or effectiveness of non-invasive ventilation (NIV) in the hospital setting for pediatric patients with respiratory distress from 1 month - 15 years of age in LMICs. All study types, including case reports and case series were included. Studies focusing exclusively on neonates (<28 days old) were excluded. Mortality and rates of adverse events were extracted using Covidence by two independent reviewers. Risk of bias was assessed using GRADE criteria for randomized control trials and a standardized risk of bias assessment tool for observational studies. The study protocol was registered on PROSPERO (CRD42018084278). Findings A total of 2174 papers were screened and 20 met criteria for inclusion. There were 5 randomized control trials (RCTs), including 3 large, well-designed RCTs. The first RCT, the ‘Bangladesh trial,’ found that children who received bubble continuous positive airway pressure (bCPAP) compared to low-flow oxygen had a significantly lower risk of failure (6% in CPAP and 24% in low-flow oxygen, p=0.0026) and mortality (4% in CPAP and 15% in low-flow oxygen, p=0.022). A second RCT, the ‘Ghana trial,’ found no decrease in all-cause mortality between the CPAP and control arms (3% and 4% respectively, p=0.11); however, an adjusted secondary analysis demonstrated decreased mortality for children under 1 year of age (3% in CPAP and 7% in control group, p=0.01). The third RCT, the ‘Malawi trial,’ compared bCPAP to low flow oxygen and found higher mortality in the bCPAP arm (17% and 11% respectively, p=0.036). Among the non-RCT studies, mortality rates ranged from 0-55%.
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    Evaluation of a Low-Cost Bubble CPAP System Designed for Resource-Limited Settings
    (Respiratory Care, 2018) Bennett, Desmond J.; Carroll, Ryan W.; Kacmarek, Robert M.
    Respiratory compromise is a leading contributor to global neonatal death. CPAP is a method of treatment that helps maintain lung volume during expiration, promotes comfortable breathing, and improves oxygenation. Bubble CPAP is an effective alternative to standard CPAP. We sought to determine the reliability and functionality of a low-cost bubble CPAP device designed for low-resource settings. METHODS: The low-cost bubble CPAP device was compared to a commercially available bubble CPAP system. The devices were connected to a lung simulator that simulated neonates of 4 different weights with compromised respiratory mechanics ( 1, 3, 5, and 10 kg). The devices’ abilities to establish and maintain pressure and flow under normal conditions as well as under conditions of leak were compared. Multiple combinations of pressure levels (5, 8, and 10 cm H2O) and flow levels (3, 6, and 10 L/min) were tested. The endurance of both devices was also tested by running the systems continuously for 8 h and measuring the changes in pressure and flow. RESULTS: Both devices performed equivalently during the no-leak and leak trials. While our testing revealed individual differences that were statistically significant and clinically important (>10% difference) within specific CPAP and flow-level settings, no overall comparisons of CPAP or flow were both statistically significant and clinically important. Each device delivered pressures similar to the desired pressures, although the flows delivered by both machines were lower than the set flows in most trials. During the endurance trials, the low-cost device was marginally better at maintaining pressure, while the commercially available device was better at maintaining flow. CONCLUSIONS: The low-cost bubble CPAP device evaluated in this study is comparable to a bubble CPAP system used in developed settings. Extensive clinical trials, however, are necessary to confirm its effectiveness.
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    How Are Insecticide-Treated Bednets Used in Ugandan Households? A Comprehensive Characterization of Bednet Adherence Using a Remote Monitor
    (The American Journal of Tropical Medicine and Hygiene, 2019) Krezanoski, Paul J.; Santorino, Data; Agaba, Alfred; Dorsey, Grant; Bangsberg, David R.; Carroll, Ryan W.
    Long-lasting insecticide-treated bednets are widely used and promoted for malaria control. Limitations in measurement methods have resulted in a poor understanding of how bednets are used in practice. We deployed a novel remote monitoring tool in Uganda to obtain, for the first time, a comprehensive characterization of bednet use in households at risk for malaria. Ten households each used one SmartNet adherence monitor over a commonly used sleeping area for 6 weeks. SmartNet continuously measures and records bednet use every 15 minutes. Bednet use was monitored for a total of 9,258 hours overall, with an average of 42 nights per household (SD: 3.5). Average duration of bednet use was 9 hours 49 minutes per night (SD: 1 hour 56 minutes), and adherence was 85–90% from 2100 to 0600. Bednets were not used at all on 4.5% (19/418) of observation nights. Overall, the average clock time that bednets were unfurled was 2034 (SD: 1 hour 25 minutes) and they were folded up at 0743 (SD: 43 minutes). The rate of interruptions per night observed in all households was 0.23 (86/369), with an average duration of 48 minutes (SD: 49 minutes). There was substantial heterogeneity between households, and some households had consistently poorer adherence relative to others. Variations in bednet use behaviors are a potentially important, and under-researched, component of long-lasting insecticide-treated bednet effectiveness. Remote bednet use monitors can provide novel insights into how bednets are used in practice, helping identify both households at risk of malaria due to poor adherence and also potentially novel targets for improving malaria prevention.
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    Inhaled Nitric Oxide as an Adjunctive Treatment for Cerebral Malaria in Children: A Phase II Randomized Open-Label Clinical Trial
    (Oxford University Press, 2015) Mwanga-Amumpaire, Juliet; Carroll, Ryan W.; Baudin, Elisabeth; Kemigisha, Elisabeth; Nampijja, Dorah; Mworozi, Kenneth; Santorino, Data; Nyehangane, Dan; Nathan, Daniel I.; De Beaudrap, Pierre; Etard, Jean-François; Feelisch, Martin; Fernandez, Bernadette O.; Berssenbrugge, Annie; Bangsberg, David; Bloch, Kenneth D.; Boum, Yap; Zapol, Warren M.
    Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM. Methods. This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate.We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment. Results. Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma Ang-1 levels increased in both treatment groups, but there was no difference between the groups at 48 hours (P = not significant [NS]). Plasma Ang-2 and cytokine levels (tumor necrosis factor-α, interferon- γ, interleukin [IL]-1β, IL-6, IL-10, and monocyte chemoattractant protein-1) decreased between inclusion and 48 hours in both treatment groups, but there was no difference between the groups (P = NS). Nitric oxide metabolite levels—blood methemoglobin and plasma nitrate—increased in patients treated with NO (both P < .05). Seven patients in the N2 group and 4 patients in the NO group died. Five patients in the N2 group and 6 in the NO group had neurological sequelae at hospital discharge. Conclusions. Breathing NO as an adjunctive treatment for CM for a minimum of 48 hours was safe, increased blood methemoglobin and plasma nitrate levels, but did not result in a greater increase of plasma Ang-1 levels at 48 hours.
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    Utility of the urine reagent strip leucocyte esterase assay for the diagnosis of meningitis in resource-limited settings: meta-analysis
    (Tropical Medicine & International Health, 2017) Bortcosh, William; Siedner, Mark; Carroll, Ryan W.
    Diagnosis of bacterial meningitis often requires cytometry, chemistry and/or microbiologic culture capabilities. Unfortunately, laboratory resources in low-resource settings (LRS) often lack the capacity to perform these studies. We sought to determine whether the presence of white blood cells in CSF detected by commercially available urine reagent strips could aid in the diagnosis of bacterial meningitis. methods We searched PubMed for studies published between 1980 and 2016 that investigated the use of urine reagent strips to identify cerebrospinal fluid (CSF) pleocytosis. We assessed studies in any language that enrolled subjects who underwent lumbar puncture and had cerebrospinal fluid testing by both standard laboratory assays and urine reagent strips. We abstracted true-positive, falsenegative, false-positive and true-negative counts for each study using a diagnostic threshold of ≥10 white blood cells per microlitre for suspected bacterial meningitis and performed mixed regression modelling with random effects to estimate pooled diagnostic accuracy across studies. results Our search returned 13 studies including 2235 participants. Urine reagent strips detected CSF pleocytosis with a pooled sensitivity of 92% (95% CI: 84–96), a pooled specificity of 98% (95% CI: 94–99) and a negative predictive value of 99% when the bacterial meningitis prevalence is 10%. conclusions Urine reagent strips could provide a rapid and accurate tool to detect CSF pleocytosis, which, if negative, can be used to exclude diagnosis of bacterial meningitis in settings without laboratory infrastructure. Further investigation of the diagnostic value of using protein, glucose and bacteria components of these strips is warranted.