Introduction: Severe vaso-occlusive pain episodes (VOE) are a major cause of morbidityand mortality in sickle cell anemia (SCA). Low arginine bioavailability is associated with pain severity and predicts need for pediatric hospitalization (Morris et al, 2000). Arginine supplementation has opioid-sparing effects and was found to significantly decrease pain scores in children hospitalized with SCA-VOE compared to placebo in a phase-2 randomized placebo-controlled trial (RCT) performed in the United States (US, Morris et al, 2013). Its role to treat acute SCA-related pain in a Sub-Saharan African country is unknown. Objectives: To determine the role of oral arginine as adjuvant in the management of SCA-VOE. Methods: A double-blind RCT of oral L-arginine (100 mg/kg/dose every 8 hours until discharge; up to 5 days/15 doses maximum) was performed in children with SCA hospitalized with severe VOE defined as a Numerical Pain Scale Score (PS) of at least 7 on a scale of 0-10, at one of two hospitals in Abuja, Nigeria. All patients received pain management (both opioids and non-opioid analgesics) per institutional practice. Demographics, clinical characteristics, length of hospital stay (LOS), pain scores, time-to-crisis-resolution (time-to-PS<4), analgesia medications required, and plasma amino acids levels were obtained before and after supplementation. Mean total analgesic medication quantification scale score (MQS), a sensitive measure to quantify analgesic use in patients with SCA, was utilized as previously described (Jacob et al, 2007). Opioid doses were calculated based on morphine equivalents in milligrams (mg). The study was performed after obtaining the National Agency for Food & Drug Administration & Control (NAFDAC) approval, Ref No. NAF/DER/CT/LAG/2017. The protocol was approved by the Human Research Ethics Committees of the University of the Witwatersrand, University of Abuja Teaching Hospital, Abuja & the National Hospital. The study was registered at the Pan African Clinical Trial Registry (PACTR 201611001864290). Results: Sixty-eight children with SCA were recruited, aged 5-17 years (mean: 10.6±0.4 years; 35 children randomized into the arginine arm & 33 into the placebo arm). Baseline characteristics were similar between arms (Table 1). MQS was significantly lower in the arginine group vs. placebo (73 [95% CI: 62-84] vs. 120 [97-143]; p<0.001). By day 5, 54% of children treated with arginine had been discharged compared to 24% in the placebo arm. Although PS were similar in both groups prior to study drug delivery (8.7±1.1 vs. 8.4±1.2, arginine vs placebo; p=0.30), worst reported PS on day 5 were lower in children treated with arginine compared to placebo (1.2±0.4 vs. 3.0±0.5; p<0.0001). The mean rate of PS decline was also greater in the arginine arm vs. placebo (1.5 [1.2-1.8) vs. 1.1 [0.9-1.2] cm/day; p=0.009). Plasma arginine levels increased by 125% vs 29% in the arginine arm vs. placebo; percent increase in arginine bioavailable inversely correlated with MSQ (r=-0.35;p=0.02). There was a non-statistically significant decrease in mean total opioid dose used in the arginine group vs. placebo (3.8 [2.7-4.9] vs 5.1 [3.8-6.5) mg/kg, p = 0.11). Patients receiving arginine had shorter time-to-crisis-resolution (p=0.0216, Fig1A), shorter LOS (p=0.015; Fig1B) and had no serious adverse events. There was 1 death in the placebo group on the second day of admission. There were no differences between groups in development of adverse events, however there was a trend towards more vomiting in the arginine arm compared to placebo (20% vs. 3%, p=0.07). Conclusion: Arginine deficiency plays a role in acute pain requiring hospitalization in Nigerian children with SCA, similar to what has been reported in the US. Plasma arginine levels significantly increased with arginine supplementation, and improved global arginine bioavailability was inversely associated with total analgesia and opioids used in VOE management. Total mean analgesia use and pain scores were lower, while time-to-crisis-resolution and LOS were shorter in children treated with arginine compared to placebo. No serious adverse events occurred in the arginine arm, while rates of adverse events were similar to placebo, providing further support for the safety of arginine therapy in children with SCA. Oral arginine is a promising adjuvant therapy for SCA-VOE management. Disclosures Morris: Pfizer: Consultancy; UCSF-Benioff Oakland: Patents & Royalties: Patents owned by UCSF-Benioff Children's Hospital Oakland regarding biomarkers and therapies that target arginine bioavailability; none are licensed and there is no royalties generated; UCSF-Benioff Children's Hospital Oakland: Patents & Royalties: Patents owned by UCSF-Benioff Children's Hospital Oakland, licensed by Lifetrients, generating royalties for nutritional supplement for autism/apraxia. OffLabel Disclosure: Oral L-arginine for treatment of acute sickle cell disease vaso-occlusive pain
Haemoglobin concentration is a clinical indicator that examines or measures the presence or otherwise of an anaemia in an individual subject particularly due to iron deficiency. Normal Haemoglobin distributions vary with age, sex, life style, race/ethnicity, socio-economic status, regional difference, drug related issues and clinical characteristics including guidelines, and protocols. Issues arising from the recent spikes in the number of new-borns who were anaemic have attracted attention globally and these are of great concern particularly in Sub-Sahara Africa in which Nigeria has huge share of statistics. Hence, this study examined haemoglobin levels in under 5 children in Nigeria and the set of factors driven it from various statistical approaches. These models were: linear regression model (LM), Linear mixed model (LMM) and multilevel model (MM). This study used dataset of children included in the Nigeria Malaria Indicator Survey, 2015. The results of LM, identified two significant predictors of under 5 children haemoglobin level, also only three predictors were significant under LMM. The random effect of household number under LMM setting had higher variability than the state as random effect. In MM with state and household number as random effects, area of residence of the child, head of household wealth index, and the age of the child were all significant. The estimates of MM produced smaller standard errors compared to LMM. This implies that multilevel model is more competitive than other models considered in this study. Therefore, it could be applied to predict the haemoglobin level of under 5 children in Nigeria.
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