Comparison of darbepoetin alpha and recombinant human erythropoietin for treatment of anemia in pediatric chronic kidney disease: a non-inferiority trial from India.

To determine whether or not Darbepoetin alpha (DA) was non-inferior to recombinant human erythropoietin (rHuEPO) in the treatment of anemia in children with chronic kidney disease (CKD) stage 3-5 (on or not on dialysis). This was a randomized, open-label, two-arm, parallel group, active-controlled, non-inferiority trial conducted at a tertiary care center in New Delhi, India. Fifty patients of either gender (aged 1-18 years) with CKD stage 3-5 (on or not on dialysis) who had baseline hemoglobin (Hb) between 9 and 12 g/dL and were on stable erythropoietin therapy for at least 8 weeks were randomized (1:1) to either continue rHuEPO or switch to DA therapy for a period of 28 weeks. Doses were titrated in the initial 23 weeks to maintain the Hb between 11 and 12 g/dL, and efficacy was assessed between weeks 24 and 28. The primary efficacy outcome was the mean change in Hb between baseline and the evaluation period. In the intention-to-treat population (n = 50), the adjusted between-group difference in mean Hb change between the baseline and the evaluation period was 0.131 g/dL (95% CI: - 0.439 to 0.719, p = 0.629). The lower limit of the two-sided 95% CI for the difference in the mean change in Hb between the two treatment groups was well above the pre-specified non-inferiority margin of - 1.0 g/dL. Similar pattern of non-inferiority was seen for per protocol population. The safety profile of DA and rHuEPO was also comparable (injection site pain:rHuEPO-3, DA-7; p-0.296).   Conclusion: DA is non-inferior to rHuEPO for the treatment of anemia of CKD (stage 3-5) in pediatric population with a comparable safety profile.   Trial registration: ClinicalTrials.gov Identifier: NCT04959578 (retrospectively registered), Date: July 13, 2021. What is Known: • Limited studies showing darbepoetin alpha is effective in children as an erythropoiesis stimulating agent. • No RCT from Indian subcontinent addressing this topic. What is New: • Darbepoetin alpha is non inferior to recombinant human erythropoietin for treatment of anemia in children with CKD stage 3-5 (on or not on dialysis) with safety comparable to recombinant human erythropoietin. • A cost reduction of approximately 8.6% per patient by shifting to darbepoetin alpha.

Quality of life in children with nephrotic syndrome: a cross-sectional study using Hindi version of PedsQL 4.0 Generic Core Scales.

BACKGROUND: Worldwide, idiopathic nephrotic syndrome (INS) is the most common glomerular disorder in children. Limited studies are available on quality of life (QOL) in children with NS, especially from developing countries. The aim of the current study was to compare the QOL of children having INS with that of matched healthy controls and to evaluate the effects of sub-types on domain scores. METHODS: This single-center, cross-sectional analytical study was conducted in children between 2 and 18 years with primary INS, at a tertiary care center in India, from September 2018 to November 2018. QOL data were collected using PedsQL™4.0 Generic Core Scales "Hindi-for-India" version (child self-report and parent-report). A total of 102 cases with equal number of matched healthy controls were included. RESULTS: The mean total PedsQL scores were lower in NS children compared to healthy controls (p-0.0004). They had statistically lower scores in physical (p- < 0.0001), social (p-0.026), and school domains (p- < 0.0001); however, no such difference was noted in emotional functioning. School functioning was the most impacted domain overall, and also across all the clinical types. Worst scores were seen in children with steroid-resistant NS in all domains. Older age-at-enrolment, higher number of relapses, prevalent NS, steroid-resistant disease, calcineurin inhibitor (CNI) use, and higher number of immunosuppressant use were important predictors of poor total QOL scores. On multivariable regression, higher number of immunosuppressant use (p-0.015) and older age-at-enrolment (p-0.016) were main predictors of impaired total scores. Cases with edema and current/previous CNI use were more likely to have impaired emotional (p-0.028) and social (p-0.040) domain sub-scores, respectively. CONCLUSION: NS has a significant impact on the QOL of children in different domains of functioning, based on their as well as parents' perspective. TRIAL REGISTRATION NO: EC/08/18/1414; Date: 30/08/2018.

Therapeutic Plasma Exchange in Children - Experience From a Tertiary Care Center.

OBJECTIVE: To assess the safety, efficacy and outcomes of therapeutic plasma exchange (TPE) in children. METHODS: Data were retrieved from hospital records for all children £18 years who underwent TPE between August, 2011 and July, 2018. RESULTS: 46 children [median (range) age 96 (8-204) months] underwent 293 sessions of TPE by membrane plasma separation technique. Renal disease was the commonest indication (24, 52.2%) followed by neurological illnesses (17; 36.9%). 36 (78.2%) patients belonged to American Society for Apheresis category I. Overall, the most common indication was atypical hemolytic uremic syndrome (aHUS) (16; 34.8%). Fresh frozen plasma plus albumin was used as replacement fluid in aHUS, while albumin was used in others. 40 (86.9%) patients had complete/partial recovery while six did not show any sign of recovery. Complications were seen in 21 (7.1%) sessions; majority of which were minor in the form of blood pressure fluctuations. CONCLUSION: TPE can be performed safely and effectively for renal and non-renal indications, even in small children.

Predictors and outcome of early extubation in infants postcardiac surgery: A single-center observational study.

OBJECTIVE: The objective of the current study was to evaluate the timing of first extubation and compare the outcome of patient extubated early with others; we also evaluated the predictors of early extubation in our cohort. MATERIALS AND METHODS: This prospective cohort study included children <1 year of age undergoing surgery for congenital heart disease. Timing of first extubation was noted, and patients were dichotomized in the group taking 6 h after completion of surgery as cutoff for early extubation. The outcome of the patients extubated early was compared with those who required prolonged ventilation. Variables were compared between the groups, and predictors of early extubation were evaluated using multivariate logistic regression analysis. RESULTS: One hundred and ninety-four (33.8%) patients were extubated early including 2 extubation in operating room and 406 (70.7%) were extubated within 24 h. Four (0.7%) patients died without extubation. No significant difference in mortality and reintubation was observed between groups. Patient extubated early had a significant lower incidence of sepsis (P = 0.003) and duration of Intensive Care Unit (ICU) stay (P = 0.000). Age <6 months, risk adjustment for congenital heart surgery category ≥3, cardiopulmonary bypass time ≥80 min, aortic cross-clamp time ≥ 60 min, and vasoactive-inotropic score >10 were independently associated with prolonged ventilation. CONCLUSION: Early extubation in infants postcardiac surgery lowers pediatric ICU stay and sepsis without increasing the risk of mortality or reintubation. Age more than 6 months, less complex of procedure, shorter surgery time, and lower inotropic requirement are independent predictors of early extubation.

Vasoactive-ventilation-renal score in predicting outcome postcardiac surgery in children.

OBJECTIVE: The objective of this study was to evaluate vasoactive-ventilation-renal (VVR) score to predict outcome postcardiac surgery in children and establish the time at which the score is best to predict outcome. MATERIALS AND METHODS: This prospective cohort included children ≤18 years recovering from cardiac surgery for congenital heart disease. Data were collected from the Intensive Care Unit (ICU) and vasoactive-inotropic score (VIS) and VVR scores calculated at admission, 24 h, and 48 h postoperatively. Outcome of interest was prolonged length of ICU stay (defined as length of stay [LOS] in the upper 25th percentile) and ICU mortality. Correlation between the outcome and scores was obtained and receiver operating characteristic (ROC) curves generated. Independent association of the scores with the outcome was also established. RESULTS: One thousand ninety-seven patients were enrolled with a median age of 24 months (range: 2 days-18 years) including 14.6% with single ventricle physiology. Pediatric ICU LOS >89 h was considered prolonged, and mortality was 2.2%. VVR score correlated better with outcome and had greater area under the curve (AUC) for ROC curve than the corresponding VIS at each study time point. The AUC of ROC curve for VVR score was greatest at 48 h for predicting both prolonged LOS (0.87) and mortality (0.92). VVR score at 48 h remains strongly associated with both prolonged LOS (odds ratio [OR] - 1.24; P = 0.000) and mortality (OR - 1.16; P = 0.000). CONCLUSION: VVR score is effective and robust bedside method to predict prolonged LOS and mortality postpediatric cardiac surgery. VVR score at 48 h was the best to predict outcome.