Eran Rom

Protracted febrile myalgia syndrome treated with pulse of corticosteroids

OBJECTIVE This study describes our 5-year experience treating protracted febrile myalgia syndrome (PFMS) with pulsed doses of corticosteroids. METHODS Eight patients with PFMS who received pulse corticosteroid therapy were identified from the electronic database of a tertiary pediatric medical center (2011-2016). Their clinical and laboratory data were collected. Differences in continuous variables between hospital admission and discharge were analyzed using Wilcoxons matched pairs test. RESULTS There were 6 female and 2 male patients of median age 10.45 years (range 6.2-17.1) Six patients were found to be homozygous for the M694V mutation. In 4 patients, PFMS was the first-ever manifestation of familial Mediterranean fever. Pulse corticosteroid therapy was administered at a dose of 10mg/kg for 3 days. Pain was alleviated (visual analog scale score, 0) within hours of initiation of therapy, although pain flare-ups lasting for minutes to hours were still observed during hospitalization. At discharge, all patients were prescribed continuous oral corticosteroids (1-2mg/kg) with gradual tapering down over 6 weeks. CONCLUSION Pulse corticosteroid therapy is effective in alleviating PFMS pain; however, it does not completely abort a PFMS episode.

Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients: A Prospective Pharmacokinetic Study

Background: Valganciclovir is extensively used for prophylaxis and treatment of cytomegalovirus (CMV) infection in solid-organ transplant recipients. However, pharmacokinetic data in children are scarce, and the pediatric dosing regimen is uncertain. This study sought to prospectively evaluate the pharmacokinetic profile, the clinical efficacy and safety of oral valganciclovir in pediatric transplant recipients and compare different dosing regimens. Methods: The cohort included solid-organ transplant recipients treated with valganciclovir for CMV prophylaxis in 2014–2015 at a tertiary pediatric medical center. All received a weight-based once-daily oral dose of 17 mg/kg. Ganciclovir concentrations were measured and the area under the curve (AUC0–24) was calculated. Results: Thirteen children of median age 7.3 years (interquartile range, 2.2–11.6) were included. Median ganciclovir AUC0–24 was 21.0 mcg·h/mL (interquartile range, 17.1–39.8); 10 patients (77%) attained AUC0–24 <40 mcg·h/mL. Exposure to ganciclovir was about 2-fold lower in young children (<9 years old; P = 0.01) and children with low body surface area (BSA; <0.7 m2; P = 0.006) than in their counterparts. Significantly lower doses were recommended with our weight-based protocol than with the manufacturer-recommended BSA- and glomerular filtration rate-based protocol (P = 0.002), reaching a 3-fold difference in infants. No evidence of CMV viremia or disease was observed while prophylaxis was given. Conclusions: The weight-based regimen of 17 mg/kg/dose oral valganciclovir results in relatively low ganciclovir exposure, especially in young children with low BSA, yet showed satisfactory clinical efficacy for CMV prophylaxis. The manufacturer’s dosing recommendation appears to result in supratherapeutic ganciclovir concentrations. Further studies are needed to establish target AUCs and valganciclovir dosing for CMV prophylaxis in pediatric transplant recipients.

Improving the Alphabet-Size in Expander-Based Code Constructions

Various code constructions use expander graphs to improve the error resilience. Often the use of expanding graphs comes at the expense of the alphabet size. In this correspondence, we show that by replacing the balanced expanding graphs used in the above constructions with unbalanced dispersers the alphabet size can be dramatically improved

Primary infection with human herpes virus type 6, post-pediatric liver transplantation - a pathogen to remember

In recent years, liver transplantation (LT) has become a well‐accepted therapeutic modality for children with end‐stage liver disease, with transplantation surgery being performed at a younger age. Human herpes virus 6 (HHV‐6) infection occurs in most children within the first 2 years of life, therefore, data on primary HHV‐6 infection in pediatric liver transplant recipients is scarce.

Risk factors for early invasive fungal infections in paediatric liver transplant recipients

Invasive fungal infections (IFIs) postliver transplantation are a frequent cause of morbidity and mortality; however, studies reporting on these infections in the paediatric population are scarce. To investigate the incidence and risk factors of IFIs in paediatric liver transplant recipients during the early posttransplantation period (≤3 months). Data were collected for all paediatric liver transplant recipients registered in a national transplantation center from 2004 to 2014. Using a stepwise logistic regression to identify independent risk factors for IFIs, a predictive model was formulated. Ten IFIs were identified in 81 liver transplant recipients (12.3%) all occurring during the first month posttransplantation. Candida species were responsible for nine cases (90%), of which four were non‐albicans Candida (44%). Significant risk factors were identified; recipient of multiple blood product transfusions during transplantation, prolonged use of indwelling intravenous catheter, prolonged IV antibiotic treatment, surgical complications, pulse steroid treatment and living donor liver transplantation. The predictive model used two clinical parameters to define high‐risk patients: a living donor transplantation and duration of IV antibiotic treatment (area under the ROC curve 0.918). IFIs are a significant complication occurring in the first month posttransplantation. Future studies are required to assess efficacy of targeted antifungal prophylaxis in high risk patients.

Children after renal transplantation hospitalized for fever: Is empirical antibiotic treatment always justified?

Infections are a major cause of morbidity and mortality after renal transplantation. However, data focusing on children are scarce. The objective of this study was to investigate the frequency and predictors of bacterial infection in pediatric renal transplant recipients in a specific setting of hospitalization due to fever. Clinical and laboratory data were retrospectively collected for all pediatric renal transplant recipients hospitalized for fever in a national renal transplantation center from 2004 to 2012. One hundred and sixty‐eight hospital admissions for fever of 52 children were analyzed. A bacterial etiology was diagnosed in 85 admissions (50.6%); 49 cases (57.6%) were documented microbiologically and 36 (42.4%) clinically. Risk factors and markers of bacterial infection included older age, presence of a central venous catheter, sonographic findings, and elevated inflammatory indices. C‐reactive protein level was a more sensitive marker than white blood cell count and absolute neutrophil count. In patients without identified risk factors, no bacterial infections were diagnosed. Pediatric renal transplant recipients hospitalized for fever are at high risk of bacterial infections and usually require empirical antibiotic treatment at admission. However, there is a minority of low‐risk patients in whom clinicians may consider withholding antibiotic treatment with close follow‐up.

Real-life comparison of three general paediatric wards showed similar outcomes for children with bronchiolitis despite different treatment regimens

This study evaluated the effectiveness of three different treatments for bronchiolitis in a tertiary paediatric facility.

WHAT IS THE APPROPRIATE VALGANCICLOVIR DOSAGE IN CHILDREN WITH SOLID ORGAN TRANSPLANT? A PROSPECTIVE PHARMACOKINETIC STUDY

Valganciclovir (VGC) is extensively used for cytomegalovirus (CMV) infection treatment and prophylaxis after solid organ transplantation (SOT). VGC dosing is problematic in children. VGC has variable absorption and is renally excreted. AUC0-24 of 40–60 mcg·h/L is a predictive pharmacokinetic parameter of efficacy and safety. Dosing based on manufacturer recommendations is supra-therapeutic in most cases. A few published dosing algorithms result in AUC out of range. Objective To prospectively validate a VGC administration dosing regimen and compare it to other dosing algorithms. Methods Children after SOT at Schneider Childrens Medical Center, the largest tertiary pediatric center in Israel, were prospectively studied, starting Dec 2014. The dosing regimen was derived from Seattle Childrens Hospital guidelines; 14–16 mg/kg/dose. For impaired renal function, stratified dose reduction was used. Blood was withdrawn at steady state: 2, 5 and 10 hours post dosing. Drug level was analyzed by HPLC. Results Nine children aged 52 (37–137) [median; (inter-quartile range)] months were studied. Four had renal and 5 had liver transplantation. VGL dose administered was 16.67 (16.42–17.72) mg/kg/dose. AUC was 20.56 (18.7–22.7) mcg·h/L. AUC was sub-therapeutic in 8 children. Manufacturer-recommended dose in our patients was suppose to be 43.5 (24.84–46.7) mg/kg/dose, significantly higher than in our study (p=0.004). Dosing based upon Asberg et al study (Pediatr. Transplantation 2014;18:103) –25.5 (19.38–25.5) mg/kg/dose, was significantly higher than in our study (p=0.009). Conclusions VGC dosing regimen in SOT children is still not clear. There are significant differences between dosing algorithms. More studies are needed. Recruitment of patients to our study continues.

PO-0206 The Effectiveness Of Various Treatment Regimens In Hospitalised Children With Bronchiolitis

Aim To evaluate the effectiveness of various treatment regimens for bronchiolitis in hospitalised children in three general paediatric wards in which different treatment protocols are customary. Patients and methods Data was retrospectively collected for all hospitalised children under two years of age with clinical bronchiolitis, between October 2012 and March 2013. Results During the study, a total of two hundred eighty six children were hospitalised with bronchiolitis in wards A, B and C. Clinical and laboratory parameters upon admission were similar among the patients in the three wards. The treatment differed between the wards, as in ward C, use of antibiotics and hypertonic saline inhalations was significantly less (p < 0.001). Admission course and outcome were also significantly different among the wards: mean number of days with measured saturation < 92% and mean length of hospital stay were lower in ward C compared to wards A and B (1.8 days vs. 2.8 and 2.9 days, p = 0.001 and 3.9 days vs. 5.0 and 4.4, p = 0.012, respectively). Multivariate analysis showed that low saturation upon admission, higher WBC count and the use of hypertonic saline inhalations were predictive of a longer period of saturation < 92% and a longer hospital stay. Similar results were found in the subgroup of two hundred and three children with positive respiratory-syncytial-virus nasal wash. Conclusions No proof was found as to the added effectiveness of different treatments in bronchiolitis. Furthermore, the use of hypertonic saline inhalations might be associated with a longer period of low saturation and a longer hospital stay.

Improving the alphabet-size in high noise, almost optimal rate list decodable codes

We revisit the construction of high noise, almost optimal rate list decodable code of Guruswami [1]. Guruswami showed that if one can explicitly construct optimal extractors then one can build an explicit