Browsing by Subject "Paediatrics"
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Item Admission EEG findings in diverse paediatric cerebral malaria populations predict outcomes(BMC, 2018-05-22) Postels, Douglas G.; Wu, Xiaoting; Li, Chenxi; Kaplan, Peter W.; Seydel, Karl B.; Taylor, Terrie E.; Kousa, Youssef A.; Idro, Richard; Opoka, Robert; John, Chandy C.; Birbeck, Gretchen L.; Medicine, School of MedicineElectroencephalography at hospital presentation may offer important insights regarding prognosis that can inform understanding of cerebral malaria (CM) pathophysiology and potentially guide patient selection and risk stratification for future clinical trials. Electroencephalogram (EEG) findings in children with CM in Uganda and Malawi were compared and associations between admission EEG findings and outcome across this diverse population were assessed. Demographic, clinical and admission EEG data from Ugandan and Malawian children admitted from 2009 to 2012 with CM were gathered, and survivors assessed for neurological abnormalities at discharge. RESULTS: 281 children were enrolled (Uganda n = 122, Malawi n = 159). The Malawian population was comprised only of retinopathy positive children (versus 72.5% retinopathy positive in Uganda) and were older (4.2 versus 3.7 years; p = 0.046), had a higher HIV prevalence (9.0 versus 2.8%; p = 0.042), and worse hyperlactataemia (7.4 versus 5.2 mmol/L; p < 0.001) on admission compared to the Ugandan children. EEG findings differed between the two groups in terms of average voltage and frequencies, reactivity, asymmetry, and the presence/absence of sleep architecture. In univariate analyses pooling EEG and outcomes data for both sites, higher average and maximum voltages, faster dominant frequencies, and retained reactivity were associated with survival (all p < 0.05). Focal slowing was associated with death (OR 2.93; 95% CI 1.77-7.30) and a lower average voltage was associated with neurological morbidity in survivors (p = 0.0032). CONCLUSIONS: Despite substantial demographic and clinical heterogeneity between subjects in Malawi and Uganda as well as different EEG readers at each site, EEG findings on admission predicted mortality and morbidity. For CM clinical trials aimed at decreasing mortality or morbidity, EEG may be valuable for risk stratification and/or subject selection.Item Global emerging resistance in pediatric infections with TB, HIV, and gram-negative pathogens(Taylor & Francis, 2021-02) Enane, Leslie A.; Christenson, John C.; Pediatrics, School of MedicineInfants, children and adolescents are at risk of life-threatening, antimicrobial-resistant infections. Global burdens of drug-resistant TB, HIV and gram-negative pathogens have a particular impact on paediatric age groups, necessitating a paediatric-focused agenda to address emerging resistance. Dedicated approaches are needed to find, successfully treat and prevent resistant infections in paediatric populations worldwide. Challenges include the diagnosis and identification of resistant infections, limited access to novel antimicrobials or to paediatric-friendly formulations, limited access to research and clinical trials and implementation challenges related to prevention and successful completion of treatment. In this review, the particular complexities of emerging resistance in TB, HIV and gram-negative pathogens in children, with attention to both clinical and public health challenges, are highlighted. Key principles of a paediatric-focused agenda to address antimicrobial resistance are outlined. They include quality of care, increasing equitable access to key diagnostics, expanding antimicrobial stewardship and infection prevention across global settings, and health system strengthening. Increased access to research studies, including clinical trials, is needed. Further study and implementation of care models and strategies for child- or adolescent-centred management of infections such as HIV and TB can critically improve outcome and avoid development of resistance. As the current global pandemic of a novel coronavirus, SARS-CoV-2, threatens to disrupt health systems and services for vulnerable populations, this is a critical time to mitigate against a potential surge in the incidence of resistant infections.Item Paediatric and obstetric outcomes at a faith-based hospital during the 100-day public sector physician strike in Kenya(BMJ Publishing Group, 2018-04-12) Adam, Mary Beth; Muma, Sarah; Modi, Jecinter Achieng; Steere, Mardi; Cook, Nate; Ellis, Wayne; Chen, Catherine T.; Shirk, Arianna; Muma Nyagetuba, John K.; Hansen, Erik N.; Pediatrics, School of MedicinePublished reviews of national physician strikes have shown a reduction in patient mortality. From 5 December 2016 until 14 March 2017, Kenyan physicians in the public sector went on strike leaving only private (not-for-profit and for-profit) hospitals able to offer physician care. We report on our experience at AIC-Kijabe Hospital, a not-for-profit, faith-based Kenyan hospital, before, during and after the 100-day strike was completed by examining patient admissions and deaths in the time periods before, during and after the strike. The volume of patients increased and exceeded the hospital's ability to respond to needs. There were substantial increases in sick newborn admissions during this time frame and an additional ward was opened to respond to this need. Increased need occurred across all services but staffing and space limited ability to respond to increased demand. There were increases in deaths during the strike period across the paediatric medical, newborn, paediatric surgical and obstetric units with an OR (95% CI) of death of 3.9 (95% CI 2.3 to 6.4), 4.1 (95% CI 2.4 to 7.1), 7.9 (95% CI 3.2 to 20) and 3.2 (95% CI 0.39 to 27), respectively. Increased mortality across paediatric and obstetrical services at AIC-Kijabe Hospital correlated with the crippling of healthcare delivery in the public sector during the national physicians' strike in Kenya.Item Predicting neurodevelopmental risk in children born to mothers living with HIV in Kenya: protocol for a prospective cohort study (Tabiri Study)(BMJ, 2022-04-04) Oyungu, Eren; El Kebbi, Ola; Vreeman, Rachel; Nyandiko, Winstone; Monahan, Patrick O.; Tu, Wanzhu; Khaitan, Alka; Desta, Zeruesenay; Slogrove, Amy L.; Humphrey, John M.; Were, Edwin; Patel, Rena C.; Carlucci, James G.; Wools-Kaloustian, Kara; McHenry, Megan S.; Pediatrics, School of MedicineIntroduction: For the growing number of children with in utero and postpartum exposure to HIV and/or antiretrovirals, it is unclear which exposures or risk factors play a significant role in predicting worse neurodevelopmental outcomes. This protocol describes a prospective longitudinal cohort study of infants born to mothers living with HIV and those born to mothers without HIV. We will determine which risk factors are most predictive of child neurodevelopment at 24 months. We aim to create a risk assessment tool to help predict which children are at risk for worse neurodevelopment outcomes. Methods and analysis: This study leverages an existing Kenyan cohort to prospectively enrol 500 children born to mothers living with HIV and 500 to those without HIV (n=1000 total) and follow them from birth to age 24 months. The following factors will be measured every 6 months: infectious morbidity and biological/sociodemographic/psychosocial risk factors. We will compare these factors between the two groups. We will then measure and compare neurodevelopment within children in both groups at 24 months of age using the Child Behaviour Checklist and the Bayley Scales of Infant and Toddler Development, third edition. Finally, we will use generalised linear mixed modelling to quantify associations with neurodevelopment and create a risk assessment tool for children ≤24 months. Ethics and dissemination: The study is approved by the Moi University's Institutional Research and Ethics Committee (IREC/2021/55; Approval #0003892), Kenya's National Commission for Science, Technology and Innovation (NACOSTI, Reference #700244) and Indiana University's Institutional Review Board (IRB Protocol #110990). This study carries minimal risk to the children and their mothers, and all mothers will provide written consent for participation in the study. Results will be disseminated to maternal child health clinics within Uasin Gishu County, Kenya and via papers submitted to peer-reviewed journals and presentation at international conferences.Item Risk factors for acute kidney injury in neonates with congenital diaphragmatic hernia(Springer Nature, 2021-08) Liberio, Brianna M.; Brinton, John T.; Gist, Katja M.; Soranno, Danielle E.; Kirkley, Megan J.; Gien, Jason; Pediatrics, School of MedicineObjective: To examine incidence of acute kidney injury (AKI), antenatal and postnatal predictors, and impact of AKI on outcomes in infants with congenital diaphragmatic hernia (CDH). Study design: Single center retrospective study of 90 CDH infants from 2009-2017. Baseline characteristics, CDH severity, possible AKI predictors, and clinical outcomes were compared between infants with and without AKI. Result: In total, 38% of infants developed AKI, 44% stage 1, 29% stage 2, 27% stage 3. Lower antenatal lung volumes and liver herniation were associated with AKI. Extracorporeal life support (ECLS), diuretics, abdominal closure surgery, hypotension, and elevated plasma free hemoglobin were associated with AKI. Overall survival was 79%, 47% with AKI, and 35% with AKI on ECLS. AKI is associated with increased mechanical ventilation duration and length of stay. Conclusion: AKI is common among CDH infants and associated with adverse outcomes. Standardized care bundles addressing AKI risk factors may reduce AKI incidence and severity.Item The feasibility of pharmacokinetic‐based dosing of hydroxyurea for children with sickle cell anaemia in Uganda: Baseline results of the alternative dosing and prevention of transfusions trial(Wiley, 2025) Power-Hays, Alexandra; Namazzi, Ruth; Dong, Min; Kazinga, Caroline; Kato, Charles; Aliwuya, Sadat; McElhinney, Kathryn; Conroy, Andrea L.; Lane, Adam; John, Chandy; Vinks, Alexander A.; Latham, Teresa; Opoka, Robert O.; Ware, Russell E.; Pediatrics, School of MedicinePharmacokinetic (PK)-guided dosing of hydroxyurea for children with sickle cell anaemia (SCA) could optimize dosing and improve outcomes, but its feasibility has not been demonstrated in low-resource settings where the majority of affected children live. Alternative Dosing And Prevention of Transfusions (ADAPT) is a prospective trial evaluating blood transfusions and the feasibility of determining PK-guided, hydroxyurea maximum tolerated doses (MTD) for children with SCA in Uganda, using portable high-performance liquid chromatography (HPLC) and a novel PK software programme (HdxSim). ADAPT enrolled 106 participants, and 100% completed PK testing. PK-guided doses were generated for 78%, of which 38% were within the protocol-defined range. Accurately, measuring serum hydroxyurea concentrations via HPLC and the potential for hydroxyurea degradation impacted the feasibility. Ensuring that people with SCA globally have access to hydroxyurea is imperative, and improving treatment strategies requires ongoing innovation including PK-guided dosing.Item Vitamin C supplementation improves placental function and alters placental gene expression in smokers(Springer Nature, 2024-10-26) Shorey-Kendrick, Lyndsey E.; McEvoy, Cindy T.; O’Sullivan, Shannon M.; Milner, Kristin; Vuylsteke, Brittany; Tepper, Robert S.; Morgan, Terry K.; Roberts, Victoria H. J.; Lo, Jamie O.; Frias, Antonio E.; Haas, David M.; Park, Byung; Gao, Lina; Vu, Annette; Morris, Cynthia D.; Spindel, Eliot R.; Pediatrics, School of MedicineMaternal smoking during pregnancy (MSDP), driven by nicotine crossing the placenta, causes lifelong decreases in offspring pulmonary function and vitamin C supplementation during pregnancy prevents some of those changes. We have also shown in animal models of prenatal nicotine exposure that vitamin C supplementation during pregnancy improves placental function. In this study we examined whether vitamin C supplementation mitigates the effects of MSDP on placental structure, function, and gene expression in pregnant human smokers. Doppler ultrasound was performed in a subset of 55 pregnant smokers participating in the "Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function" (VCSIP) randomized clinical trial (NCT01723696) and in 33 pregnant nonsmokers. Doppler ultrasound measurements showed decreased umbilical vein Doppler velocity (Vmax) in placebo-treated smokers that was significantly improved in smokers randomized to vitamin C, restoring to levels comparable to nonsmokers. RNA-sequencing demonstrated that vitamin C supplementation to pregnant smokers was associated with changes in mRNA expression in genes highly relevant to vascular and cardiac development, suggesting a potential mechanism for vitamin C supplementation in pregnant smokers to improve some aspects of offspring health.