Browsing by Author "Opoka, O. Robert"

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    Early weaning from oxygen therapy in African children with severe pneumonia.
    (BMC Medicine, 2025) Maitland, Kathryn; Giallongo, Elisa; Hamaluba, Mainga; Alaroker, Florence; Opoka, O. Robert; Tagoola, Abner; Nalwanga, Damalie; Nabawanuka, Eva; Okiror, William; Nakuya, Margaret; Aromut, Denis; Williams, N. Thomas; Thomas, Karen; Harrison, A. David; Mouncey, Paul; Bush, Andrew; Fraser, F. J.; Rowan, Kathy; Olupot‑Olupot, Peter; Kiguli, Sarah
    Background: In Africa, severe pneumonia remains the major cause of paediatric hospitalisation, resulting in high requirements for oxygen therapy. Adequate supplies of oxygen are key challenges for many low-resource hospitals. The World Health Organization manual for oxygen therapy advises 2–3 days of oxygen therapy for pneumonia and recommends against early weaning, even in the absence of hypoxaemia. Few data support this recommendation. We describe the oxygen use and timing of weaning in the COAST trial of oxygen therapy (ISRCTN15622505). Methods: Children aged 28 days to 12 years presenting to 6 hospitals in Uganda and Kenya with severe pneumonia and hypoxaemia (saturations<92% on pulse oximetry (SpO2) were eligible for the trial. Children in two strata (a) severe hypoxaemia (SpO2<80%) and (b) moderate hypoxaemia (SpO2 80–91%) were allocated to receive high flow nasal therapy (HFNT), low flow oxygen delivery (LFO) or control (no immediate oxygen (moderate hypoxaemia stratum only)). Children were closely monitored over 48 h by pulse oximetry and weaned off oxygen once ­SpO2>92%. We describe the oxygen use and proportion requiring respiratory support over time by intervention strategy. Results: Of the 1842 children enroled the majority, 1454 (79%) had moderate hypoxaemia. In this stratum, by 2 and 8 h, 148 (41%) and 200/360 (55.6%) in the LFO arm had been weaned; in the HFNT arm, 213/362 (59%) were receiving respiratory support at 2 h in room alone, and by 8 h, 164/362 (45%) had been weaned. At 48 h, in the respective strata, 77–80% and 53–63% still had respiratory distress but without hypoxaemia and were thus not receiving oxygen. Median oxygen use at 48 h in the moderate hypoxaemia group was highest in LFO am 480L (IQR 236.2, 2132.2) compared to 113.4 L (IQR 0.0, 1453.9) in the HFNT and 0 L (IQR 0.0) in the control arms. Children requiring oxygen beyond 48 h, 17/33 (51.1%) and 9/46 (19.5%) in the respective strata, had additional cardiac conditions. Conclusions: Closely monitoring SpO2 resulted in early weaning and reduced the use of and exposure to oxygen. Where oxygen supplies are at a premium, this approach may improve equitable access for children with severe pneumonia. Keywords Severe pneumonia, African children, Oxygen therapy, High flow nasal therapy
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    Hydroxyurea pharmacokinetics in children with sickle cell anemia across different global populations
    (PubMed Central, 2025) Power-Hays, Alexandra; McElhinney, E. Kathryn; Williams, N. Thomas; Mochamah, George; Olupot-Olupot, Peter; Paasi, George; Reid, E. Marvin; Rankine-Mullings, E. Angela; Opoka, O. Robert; John, C. Chandy; McGann, T. Patrick; Quinn, T. Charles; Punt, C. Nieko; Smart, R. Luke; Latham, S. Teresa; Vinks, A. Alexander; Ware, E. Russell
    Hydroxyurea provides effective disease-modifying treatment for people with sickle cell anemia (SCA), especially when escalated to maximum tolerated dose (MTD), which has wide interpatient dosing variability due to pharmacokinetic (PK) differences. Whether hydroxyurea PK parameters differ among children with SCA in different global regions is unknown. We compared hydroxyurea PK parameters among children with SCA from 5 clinical trials: HUSTLE (United States), TREAT (United States), NOHARM (Uganda), REACH (Uganda and Kenya), and EXTEND (Jamaica). Key hydroxyurea PK parameters were determined using HdxSim, a validated hydroxyurea PK software program. The results were compared across regions by analysis of variance. PK profiles from 451 children with SCA (146 from the United States, 265 from Africa, and 40 from the Caribbean) were included. Children from Africa had slightly lower volumes of distribution, but absorption rate and clearance were similar across regions. The PK-recommended doses to achieve MTD were statistically different but clinically similar across the United States (26.6 ± 5.9 mg/kg per day), Africa (27.6 ± 6.5 mg/kg per day), and the Caribbean (25.2 ± 4.7 mg/kg per day) (P = .04). In multivariable regression, younger age and increased reticulocyte counts were associated with higher PK-recommended doses. Hydroxyurea PK parameters in children with SCA differ minimally across global populations, predicting clinically similar doses to achieve MTD. Individualized hydroxyurea dosing based on a PKpopulation model derived from US children with SCA can be used broadly to maximize the benefits of this critical medication in other global populations. These trials were registered at www.ClinicalTrials.gov as #NCT00305175 (HUSTLE), #NCT02286154 (TREAT), #NCT01976416 (NOHARM), #NCT01966731 (REACH), and #NCT02556099 (EXTEND).