Filtered sunlight versus intensive electric powered phototherapy in moderate-to-severe neonatal hyperbilirubinaemia: a randomised controlled non-inferiority trial.

BACKGROUND: Kernicterus resulting from severe neonatal hyperbilirubinaemia is a leading cause of preventable deaths and disabilities in low-income and middle-income countries, partly because high-quality intensive phototherapy is unavailable. Previously, we showed that filtered-sunlight phototherapy (FSPT) was efficacious and safe for treatment of mild-to-moderate neonatal hyperbilirubinaemia. We aimed to extend these studies to infants with moderate-to-severe hyperbilirubinaemia. METHODS: We did a prospective, randomised controlled non-inferiority trial in Ogbomoso, Nigeria-a simulated rural setting. Near-term or term infants aged 14 days or younger who were of 35 weeks or more gestational age and with total serum bilirubin concentrations at or above the recommended age-dependent treatment levels for high-risk neonates were randomly assigned (1:1) to either FSPT or intensive electric phototherapy (IEPT). Randomisation was computer-generated, and neither clinicians nor the parents or guardians of participants were masked to group allocation. FSPT was delivered in a transparent polycarbonate room lined with commercial tinting films that transmitted effective phototherapeutic light, blocked ultraviolet light, and reduced infrared radiation. The primary outcome was efficacy, which was based on assessable treatment days only (ie, those on which at least 4 h of phototherapy was delivered) and defined as a rate of increase in total serum bilirubin concentrations of less than 3·4 µmol/L/h in infants aged 72 h or younger, or a decrease in total serum bilirubin concentrations in those older than 72 h. Safety was defined as no sustained hypothermia, hyperthermia, dehydration, or sunburn and was based on all treatment days. Analysis was by intention to treat with a non-inferiority margin of 10%. FINDINGS: Between July 31, 2015, and April 30, 2017, 174 neonates were enrolled and randomly assigned: 87 to FSPT and 87 to IEPT. Neonates in the FSPT group received 215 days of phototherapy, 82 (38%) of which were not assessable. Neonates in the IEPT group received 219 treatment days of phototherapy, 67 (31%) of which were not assessable. Median irradiance was 37·3 µW/cm2/nm (IQR 21·4-56·4) in the FSPT group and 50·4 µW/cm2/nm (44·5-66·2) in the IEPT group. FSPT was efficacious on 116 (87·2%) of 133 treatment days; IEPT was efficacious on 135 (88·8%) of 152 treatment days (mean difference -1·6%, 95% CI -9·9 to 6·7; p=0·8165). Because the CI did not extend below -10%, we concluded that FSPT was not inferior to IEPT. Treatment was safe for all neonates. INTERPRETATION: FSPT is safe and no less efficacious than IEPT for treatment of moderate-to-severe neonatal hyperbilirubinaemia in near-term and term infants. FUNDING: Thrasher Research Fund and National Center for Advancing Translational Sciences.

Glucose-6-phosphate dehydrogenase deficiency in Nigerian children.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy and in Sub-Saharan Africa, is a significant cause of infection- and drug-induced hemolysis and neonatal jaundice. Our goals were to determine the prevalence of G6PD deficiency among Nigerian children of different ethnic backgrounds and to identify predictors of G6PD deficiency by analyzing vital signs and hematocrit and by asking screening questions about symptoms of hemolysis. We studied 1,122 children (561 males and 561 females) aged 1 month to 15 years. The mean age was 7.4 ± 3.2 years. Children of Yoruba ethnicity made up the largest group (77.5%) followed by those Igbo descent (10.6%) and those of Igede (10.2%) and Tiv (1.8%) ethnicity. G6PD status was determined using the fluorescent spot method. We found that the overall prevalence of G6PD deficiency was 15.3% (24.1% in males, 6.6% in females). Yoruba children had a higher prevalence (16.9%) than Igede (10.5%), Igbo (10.1%) and Tiv (5.0%) children. The odds of G6PD deficiency were 0.38 times as high in Igbo children compared to Yoruba children (p=0.0500). The odds for Igede and Tiv children were not significantly different from Yoruba children (p=0.7528 and 0.9789 respectively). Mean oxygen saturation, heart rate and hematocrit were not significantly different in G6PD deficient and G6PD sufficient children. The odds of being G6PD deficient were 2.1 times higher in children with scleral icterus than those without (p=0.0351). In conclusion, we determined the prevalence of G6PD deficiency in Nigerian sub-populations. The odds of G6PD deficiency were decreased in Igbo children compared to Yoruba children. There was no association between vital parameters or hematocrit and G6PD deficiency. We found that a history of scleral icterus may increase the odds of G6PD deficiency, but we did not exclude other common causes of icterus such as sickle cell disease or malarial infection.

A randomized pahse I bioequivalence clinincal trial of a paediatric fixed-dose combination antiretroviral reconstitutable suspension in healthy adult volunteers.

BACKGROUND: This study aimed to test the hypothesis that the paediatric fixed-dose combination granule for reconstitution (comprising lamivudine/zidovudine/nevirapine 30/60/50 mg per 5 ml) as a test product is bioequivalent to the coadministered single entities of the referenced products. Fixed-dose combination anti-retroviral therapy provides adequate suppression of HIV-1 replication, provides barrier to the development of resistance, simplifies dosage regimen and improves adherence. METHODS: An open label, randomized, two-way crossover study was conducted on 24 health adults under fasted conditions, with a washout period of 14 days between treatments. A total of 15 blood samples were collected before dosing and up to 96 h post dosing. The drugs were extracted from plasma and anlaysed using a validated high performance liquid chromatography- ultraviolet method. Non- compartmental pharmacokinetic (PK) analysis was performed to obtain the PK parameters, maximum plasma concentration (C max), area under the curve of plasma concentration-time curves from the time zero to last measurable concentration (AUC0-t) and the area under the curve extrapolated to infinity (AUC 0-∞) ANOVA test was performed to determine the effect of model factors on the PK parameters. The two one-sided t-tests were performed on the log-transformed data to determine the 90% CL for the ratio of test to reference PK parameters. RESULTS: The drugs were well tolerated and safe with minimal adverse events. The ANOVA test indicated the absence of any significant effects ( P>0.05) due to the model parameters. The 90% Cl for the geometric mean ratio of the test/reference for the Cmax, AUC0-t and the AUC0-∞ for lamivudine, zidovudine and nevirapine were within 80-125% bioequivalence limits. CONCLUSIONS: This single dose randomized study found that the test and reference products met the criteria for bioequivalence in the fasting healthy adult volunteers.