Side Effects In Children Research Articles

Assessment of Behavior Abnormalities of Corticosteroids in Children with Nephrotic Syndrome

Introduction. The objective of this work was to define the frequency and severity of steroid related behavioral side effects in children with steroid sensitive idiopathic nephrotic syndrome (SSNS) during Treatment for relapse. Methods. 30 pediatric patients with steroid sensitive nephrotic syndrome were studied; known as SSNS at complete remission or low dose of Prednisolone and have relapse on follow up. All children in this study were subjected to full history taking, thorough clinical examination, assessment socioeconomic standard, and assessment of pediatric quality of life, a battery of psychometric tests included pediatric anxiety, depression, and aggression scores. Results. Our results revealed that there are highly significant increase in the mean values of anxiety, depression and aggression among cases starts to appear on week one and extends to three, five and seven weeks compared to baseline. In the seventh week of follow up cases show significant positive correlation between prednisone doses and mean values of anxiety and depression scores and aggression. Conclusion. we concluded that all studied children with SSNS often experience significant problems with anxiety, depression, and increased aggression during high dose steroid therapy.

Abstract 4520: Nanotechnology based drug delivery in childhood leukemia therapy: A novel approach to reduce side-effects.

Abstract Despite attaining 5-year survival rates of 90%; more than 60% of pediatric cancer survivors are affected by at-least one life threatening event in their lifetime. Childhood leukemia is currently treated with a combination of chemotherapeutics that are effective in combating the disease. However, these drugs also affect the normal growing cells in children causing devastating side-effects. The goal of this study is to develop nanosized drug delivery formulations that deliver drugs specifically to leukemic cells and ultimately reduce treatment related side-effects in children. Multi-step chemical transformations were employed to construct amphiphilic block copolymers consisting of hydrophilic polyether (PEG) and hydrophobic polyester (PCL) bearing pendent cyclic ketals. The functional block copolymers self-assemble into micelles with a core-shell architecture comprising a segregated PCL core that encapsulates the steroid drug (Dexamethasone) and a sterically stabilized PEG shell that provides a platform to conjugate targeting moieties. Dexamethasone (Dex) and fluorescent-dye encapsulated nanoparticles (NPs) were formulated by a nanoprecipitation method. The size and morphology of all formulations were analyzed by dynamic light scattering (DLS) and transmission electron microscopy (TEM) methods. The non-toxic nature of the blank-NPs was confirmed both in vitro and in vivo. The drug encapsulated NPs (Dex-NPs) are endocytosed into leukemic cells and induced cytotoxicity similar to that of free Dex, but at reduced doses. The Dex-NPs significantly improved survival in preclinical mouse models of leukemia. A second generation drug encapsulated targeted NPs with transferrin as the targeting moiety improved NP uptake in leukemic cells by comparison to non-targeted NPs. The demonstrated efficacy of such novel nanotherapeutic systems in vitro and in pre-clinical mouse models of acute leukemia have provided the foundation to successfully create novel therapeutic delivery systems that target and treat pediatric hematological malignancies with enhanced efficacy and reduced toxicity. Citation Format: Vinu Krishnan, Xian Xu, Sonali Barwe, Xiaowei Yang, Scott A. Waldman, Robert W. Mason, Xinqiao Jia, Ayyappan K. Rajasekaran. Nanotechnology based drug delivery in childhood leukemia therapy: A novel approach to reduce side-effects. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4520. doi:10.1158/1538-7445.AM2013-4520

Efficacy of dexmedetomidine addition to bupivacaine on the quality of blind fascia iliaca compartment block in children undergoing femur fracture surgery

Efficacy of dexmedetomidine addition to bupivacaine on the quality of blind fascia iliaca compartment block in children undergoing femur fracture surgery.ObjectivesThe objectives of this study were designed to detect the effects of addition of dexmedetomidine to bupivacaine on the quality of blind fascia iliaca compartment block and its possible side effects in children undergoing fracture femur surgery.MethodsThis study was conducted on 28 children (2–6 years of age), scheduled for fracture femur surgery. Children were randomly allocated to receive either 0.25% bupivacaine 1 ml kg−1 (B group), or 0.25% bupivacaine 1 ml kg−1 with dexmedetomidine 2 μg kg−1 (BD group). Anesthesia was maintained with sevoflurane 1–1.5 minimum alveolar concentration. Intraoperative sevoflurane concentration, hemodynamic, postoperative emergence delirium, sedation scores and pain scores were recorded. Duration of surgery and emergence time were recorded. Postoperative complications such as (nausea and vomiting, respiratory depression, purities, hypotension and bradycardia) were reported.ResultsCompared to the group B, patients received bupivacaine–dexmedetomidine for fascia iliaca compartment block had lower intraoperative sevoflurane concentration, higher sedation score, longer duration of postoperative analgesia, less use of rectal paracetamol for the first 24 h postoperatively and less number with postoperative agitation. No patients developed postoperative respiratory depression, purities, hypotension or bradycardia.ConclusionThe present study concluded that the combined use of bupivacaine–dexmedetomidine for fascia iliaca compartment block in children provided significant reduction of end-tidal sevoflurane concentration, remarkable hemodynamic stability, significant postoperative analgesia with lower postoperative analgesics requirements without any undesirable complications.

COMT rs4680 variant and cardiometabolic side‐effects in children treated with second‐generation antipsychotics

Second‐generation antipsychotics (SGA) are used to treat children for a wide‐range of mental health conditions but are associated with side effects such as rapid weight gain; increased waist circumference; and elevated fasting plasma glucose, blood pressure, and metabolic syndrome (MetS). The aim of this study is to investigate the interaction of the rs4680 variant in the catechol‐ O‐methyltransferase gene (COMT) and SGA treatment on cardiometabolic side‐effects in a cross‐sectional population of SGA‐treated (n=99) and SGA–naïve (n=114) children. SGA‐treated children had higher (P<0.05) BMI z‐scores, systolic blood pressure (SBP) z‐scores, and fasting plasma glucose and total and LDL‐cholesterol concentrations than SGA‐naïve children. Fifteen percent of SGA‐treated children had MetS compared to 2% of SGA‐naïve children (P=0.001). The COMT rs4680 variant genotype frequencies were not different between SGA‐treated (AA 24.2%, AG 50.5%, GG 25.3%) and SGA‐naïve (AA 24.6%, GA 45.6%, GG 29.8%) children. An interaction between SGA‐treatment and COMT rs4680 genotype was observed such that SGA‐treated children with the AA genotype had higher SBP, fasting plasma insulin, and HOMA‐IR than those with the GG genotype. The opposite effect was observed in SGA‐naïve children. These findings suggest that the COMT rs4680 variant may interact with SGAs and contribute to cardiometabolic side‐effects in children.

The Fat Mass and Obesity Associated (FTO) rs9939609 Variant and Cardiometabolic Side-effects in Children Treated With Second-Generation Antipsychotics

The Fat Mass and Obesity Associated (FTO) rs9939609 Variant and Cardiometabolic Side-effects in Children Treated With Second-Generation Antipsychotics

Clinical Controversies: Proton Therapy for Pediatric Tumors

Despite the claim in the published literature, the introduction of proton therapy for children is not analogous to the evolution of conformal photon irradiation relying on the understanding of the impact of altered dose distributions. The differences in radiobiological effect when comparing photons with protons mean that we are comparing a known entity with an unknown entity: the dose-volume histogram for proton therapy might mean something substantially different from the dose-volume histogram for photon therapy. The multifaceted difference between the 2 modalities supports the argument for careful evaluation, follow-up, and clinical trials with adverse event monitoring when using proton therapy in children. We review the current data on the outcome of proton therapy in a range of pediatric tumors and compare them with the often excellent results of photon therapy in the setting of multidisciplinary management of childhood cancer. It is hoped that the apparent dosimetric advantage of proton therapy over photons will lead to improved indications for therapy, disease control, and functional outcomes. Although physical dose distribution is of clear importance, the multimodality management of children by an expert pediatric oncology team and the availability of ancillary measures that improve the quality of treatment delivery may be more important than the actual beam. In addition, current estimates of the benefit of proton therapy over photon therapy based on toxicity reduction will only be realized when survivorship has been achieved. Once substantive proton therapy data become available, it will be necessary to demonstrate benefit in clinically relevant outcome measures in comparison with best existing photon outcome data. Such an effort will require improved funding and appreciation for late effects research. Only real clinical outcome data combined with better understanding of the radiobiological differences between protons and photons will help us to further reduce side effects in children and exploit the full curative potential of this relatively new modality.

Asthma in school‐aged children, it's time to reveal its entities

Asthma in school‐aged children, it's time to reveal its entities

Gastrointestinal side effects in children with Wilson's disease treated with zinc sulphate

To investigate the side effects of a zinc sulphate therapy in a cohort of Polish pediatric patients with Wilson's disease. We retrospectively analyzed a cohort of 53 pediatric patients with Wilson's disease treated at the Children's Memorial Health Institute in Warsaw, Poland between the years 1996 and 2011 with zinc sulphate. Patients were diagnosed with Wilson's disease according to the scoring system of Ferenci, with 49 cases confirmed by mutation analysis. Data about the dosage scheme of zinc sulphate, side effects and efficacy and toxicity of the treatment were collected and recorded in the patient's medical chart at each visit to the hospital. Mean age of diagnosis for the entire cohort was 10 years (range, 2.5-17 years). Duration of treatment with zinc sulfate was 83.3 wk (range, 8-344 wk). Side effects, all of gastrointestinal origin, were observed in 21 patients (40%--9 males and 12 females), irrespective of the duration of therapy. Thirteen out of 21 patients were over the age of 10 years. The most common ATP7B mutation was p.H1069Q. Esophagogastroduodenoscopy, performed in 7 patients (33.3%) suffering from persistent and severe abdominal pain, revealed gastrointestinal ulcerations or erosions with negative Helicobacter pylori tests in all subjects investigated. The above mentioned 7 patients were treated with proton pump inhibitors. Three of those experienced resolution of symptoms, whereas proton-pump inhibitors failed to alleviate symptoms of the remaining four children and conversion of therapy to D-penicillamine was needed. Zinc sulphate appears to cause significant gastrointestinal side effects, which children on therapy for Wilson's disease should be closely monitored for.

Safety and efficacy of high‐dose tamoxifen and sulindac for desmoid tumor in children: Results of a Children's Oncology Group (COG) Phase II Study

Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non-cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children's Oncology Group. Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression-free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging. Fifty-nine eligible patients were enrolled from 2004 to 2009; 78% were 10-18 years old. Twenty-two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life-threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2-year PFS and survival rates were 36% (95% confidence interval: 0.23-0.48) and 96%, respectively. All three deaths were due to progressive DT. Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates.

Are Colony Stimulating Factors (G-CSF) Still Needed in Treatment of Severe Aplastic Anemia in Children?

AbstractAbstract 4400 Objective.Allogenic bone marrow transplantation is the first choice in children with severe acquired aplastic anemia (SAA), but if there is no matched sibling donor, the immunosuppressive therapy (IST) which consists of ATG combined with cyclosporine A, steroids and/or colony stimulating factors (G-CSF), is the best way of treatment.In last two decades there was a trend to add G-CSF to combination of ATG and CSA. Nowadays there is much uncertainty about this practice. There are discussion whether it really reduces early infectious mortality. There are suggestions too, that long term using of G-CSF can play role in developing clonal disorders. Aim.The aim of this study was to assess the influence of period of using colony stimulating factors for the event free survival (EFS), and progression free survival (PFS), infectious side effects, clonality and relapses in patients with SAA. Methods.The group of 55 children with SAA and vSAA (23 girls and 32 boys,) were retrospectively analyzed. The median age of children was 10 years (range 6mth-17,5 years). IST (Thymoglobuline, steroids, CSA, and/or GSF-CS) was given according to the protocol of The European Blood and Marrow Transplant (EBMT) Severe Aplastic Anemia Working Party.G-CSF was administered at the dose of 5μg/kg/mc, in 52 patients. The median period of administration was 32 days (range 0–187 days)The response to the treatment was assessed on 84, 112,180 and 360 day. Relative risk test and Kaplan–Meier estimator, the univariate analysis and multivariate Cox regression models, test were used to estimate the influence of the period of G-CSF therapy for EFS, PFS, relapse free survival, clonality, toxicity and other side effects in children with aplastic anemia Results.The 2- year probability of event free survival (EFS) was 71,52%. The 5 and 10 –year EFS was 57,7%. Progression free survival (PFS) was 66,53%, at 2 years and 59,13% at 5- and 10 years. The relapse rate was 1,81%. The 2-year probability of not having relapse was 87,68%. Relapse free survival was 75,16% at 5 and 10 years. There was 15 deaths (27,27%), 5 early and 10 late deaths. Infections were the main causes of death. There was one transformation to paroxysmal nocturnal haemoglobinuria (PNH) and no transformation to MDS or AML. There was no significant correlation between EFS, PFS and the duration of G-CSF treatment (p > 0,05 log rank). There was tendency for longer PFS and EFS in patient who had G-CSF administered for shorter period. Relative risk (RR) for patients who didn’t receive G-CSF was connected with 28% lower infection rate. RR for children receivingG-CSF for 1–10 days was 0,55.No infectious episodes were observed in children who were treated with G-CSF for 11 – 21 days. RR for patients treated from 21 to 28 day was 1,71. Patients who were given G-CSF for more than 28 days had RR=1,15. During the G-CSF therapy we observed muscular pains, and capillary leak syndrome, but these side effects didn’t influence survival (p>0,05 log-rank) Conclusions.The duration of G-CSF therapy has no impact on the survival (EFS, PFS), but it is a significant factor concerning infection rate. Colony stimulating factor shouldn't be routinely used. Period of administration should be as short as possible. Disclosures:No relevant conflicts of interest to declare.

Management of Psychotropic Medication Side Effects in Children and Adolescents

This article is a review of several of the most concerning side effects of psychotropic medications in children and adolescents. An emphasis is placed on review of the prevalence, presentation, monitoring, and evidence-based management of these side effects.

Effect of oral dextromethorphan versus oral ketamine on sevoflurane related emergence agitation in children undergoing adenotonsillectomy

BackgroundEmergence agitation is a popular phenomenon after sevoflurane anesthesia. Our aim was to study the efficacy of oral dextromethorphan compared to oral ketamine on sevoflurane related agitation.MethodsIn a prospective, randomized, double- blinded study 120, ASA I, aged 4–10 years old children undergoing adenotonsillectomy were randomly divided into three groups to receive oral dextromethorphan 1 mg/kg (Group D, n = 39), oral ketamine 5 mg/kg (Group K, n = 39) or placebo(Group C, n = 38) as premedication 1 h before surgery. Standard general anesthesia was induced and maintained with sevoflurane in N2O/O2. The following were recorded by a blinded anesthetist; Child separation and cooperation at induction, duration of operation, duration of anesthesia, duration of extubation, duration of emergence, state of emergence on admission to PACU using emergence agitation scale, number of patients required postoperative fentanyl to control agitation, duration of discharge from PACU, vital signs (heart rate, blood pressure, and Spo2) in PACU, and side effects (Nausea, vomiting, respiratory depression, and hallucination).ResultsThe agitated patients that required fentanyl treatment were statistically significant low in groups D and K compared to group C (p < 0.05). Child separation and child cooperation at induction from parents was successful in all children in group K with statistical significant difference compared to other groups (p < 0.05). There were increases in duration of anesthesia, extubation, and emergence in group K compared to other groups without increase in the duration of stay in PACU.ConclusionOral premedication with either dextromethorphan 1 mg/kg or ketamine 5 mg/kg were comparable in reducing significantly the incidence of postoperative sevoflurane related emergence agitation in comparison to placebo treated group without reported side effects in children undergoing adenotonsillectomy.

Weight gain and metabolic side effects with antipsychotic drugs in children

BackgroundWeight gain and metabolic side effects are some of the most troublesome side effects of atypical antipsychotics, especially when used in children and adolescents. There have been few studies on these side effects in children in Arab countries.ObjectivesTo determine weight gain and metaboli

1827 An Experience of Usage of Acellular DTAP Vaccine in Children Over 4 Years Old

Actuality:Pertussis is a high contagious bacterial infection with an air-drop way of transmission, remains a serious problem as in Russia, as all over the world. The only reliable way of...

New scale for assessing epilepsy drug side effects in children

New scale for assessing epilepsy drug side effects in children

025 FTO rs9939609 Variant Does Not Predict Cardiometabolic Side-Effects in Children Treated With Second-Generation Antipsychotics

025 FTO rs9939609 Variant Does Not Predict Cardiometabolic Side-Effects in Children Treated With Second-Generation Antipsychotics

Development and validation of the Pediatric Epilepsy Side Effects Questionnaire

To develop and validate a measure of antiepileptic drug (AED) side effects in children with a variety of seizure types, treatments, and therapy durations. Content for an initial 44-item measure was developed using the previously published Hague Scale and expert opinion from recognized pediatric epileptologists (n = 12) and caregivers of children with epilepsy (n = 21). The measure was completed by caregivers during routine clinic visits. Demographic and medical data were collected through chart reviews. Factor analysis was conducted and internal consistency, test-retest reliability, and construct validity were assessed. Questionnaires were analyzed from 495 children with epilepsy (M(age) = 10.1 years; range 2-21 years; 42% female; 14% African American; 32% new onset vs 68% chronic epilepsy). The final questionnaire, the Pediatric Epilepsy Side Effects Questionnaire (PESQ), is a 19-item measure with 5 subscales (i.e., cognitive, motor, behavioral, general neurological, and weight) that accounts for 99% of the variance. Internal consistency coefficients and test-retest reliabilities ranged from 0.72 to 0.93 and 0.74 to 0.97, respectively. Construct validity was demonstrated by increasing side effects as the number of drugs increased. Participants on valproic acid had significantly higher scores on the Weight Scale compared to those on carbamazepine. The PESQ is a reliable and valid measure of AED side effects in children across the epilepsy spectrum that can be used in both clinical and research settings.

The Optimal Dose of Prophylactic Intravenous Naloxone in Ameliorating Opioid-Induced Side Effects in Children Receiving Intravenous Patient-Controlled Analgesia Morphine for Moderate to Severe Pain

The Optimal Dose of Prophylactic Intravenous Naloxone in Ameliorating Opioid-Induced Side Effects in Children Receiving Intravenous Patient-Controlled Analgesia Morphine for Moderate to Severe Pain

Imaging Changes in Very Young Children with Brain Tumors Treated with Proton Therapy and Chemotherapy

PT promises to reduce side effects in children with brain tumors by sparing normal tissue compared with 3D conformal or intensity-modulated radiation therapy. Information is lacking about the combined effects of PT and chemotherapy in young children. We describe imaging changes in 8 very young children with localized brain tumors who received PT after chemotherapy. Mostly transient signal abnormalities and enhancement in brain parenchyma were observed by serial MR imaging, which were consistent with radiation-induced effects on normal-appearing tissue. Correlation with PT planning data revealed that the areas of imaging abnormality were located within or adjacent to the volume that received the highest radiation dose. Radiologists should be aware of these findings in children who receive PT after chemotherapy. In this report, we describe the time course of these PT-related imaging findings and correlate them with treatment and clinical outcomes.

Cardioprotection and safety of dexrazoxane (DRZ) in children treated for newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or advanced stage lymphoblastic leukemia (T-LL).

9504 Background: POG 9404 evaluated the efficacy of DRZ as a cardioprotectant and its side effects in children receiving doxorubicin (DOX) as part of chemotherapy for T-ALL/T-LL. Methods: Between 6/1996 and 9/2001, 537 T-ALL/T-LL patients were treated with multi-agent chemotherapy that included 12 DOX doses of 30 mg/m2. Patients were randomized at diagnosis to treatment with or without DRZ (300 mg/m2 IV immediately prior to each DOX dose). Cardiac effects were assessed by serial echocardiograph measurements of left ventricular (LV) function (fractional shortening) and structure (end-diastolic dimension, wall thickness, and mass). Adverse events, grades 3-5 were recorded using CTCAE version 2.0. Results: Five-year EFS was similar for the DRZ (0.77±0.03%) and no-DRZ (0.76±0.03%) groups (p=0.9). Acute cardiac toxicity occurred in 1 patient (arrhythmia) on DRZ and 4 patients treated without DRZ (1-arrhythmia, 3-decreased LV fractional shortening). At each of the three time-points post-baseline (end-induction, after the last DOX dose and two years post study entry) LV dimensions were larger from baseline for patients who did not receive DRZ. In univariate analyses, change in LV end-diastolic dimension from baseline was the only variable that was significantly different between DRZ and no-DRZ arms. This was true at each of the three time points (p=0.005-0.02). The frequencies of grade 3 or 4 toxicity (hematologic, infection, CNS events, mucositis) or death were similar in groups with or without DRZ (p&lt;0.24). There were 13 second malignancies, 10 patients had received DRZ and 3 had not (p=0.07). Conclusions: Our LV dimension measurements suggest that DRZ may protect against the early LV remodeling and enlargement that is seen with DOX cardiotoxicity. Addition of DRZ did not interfere with the anti-tumor efficacy of this DOX-containing, multi-agent regimen, and there was no significant increase in toxicities. An increased rate of second malignancies with DRZ did not reach conventional levels of statistical significance. The study was not powered to assess second malignancy rates and this trend is of unknown clinical significance.