Adverse Effects In Children Research Articles

Mass deworming to improve developmental health and wellbeing of children in low-income and middle-income countries: a systematic review and network meta-analysis.

Soil-transmitted helminthiasis and schistosomiasis, considered among the neglected tropical diseases by WHO, affect more than a third of the world's population, with varying intensity of infection. We aimed to evaluate the effects of mass deworming for soil-transmitted helminths (with or without deworming for schistosomiasis or co-interventions) on growth, educational achievement, cognition, school attendance, quality of life, and adverse effects in children in endemic helminth areas. We searched 11 databases up to Jan 14, 2016, websites and trial registers, contacted authors, and reviewed reference lists. We included studies published in any language of children aged 6 months to 16 years, with mass deworming for soil-transmitted helminths or schistosomiasis (alone or in combination with other interventions) for 4 months or longer, that reported the primary outcomes of interest. We included randomised and quasi-randomised trials, controlled before-after studies, interrupted time series, and quasi-experimental studies. We screened in duplicate, then extracted data and appraised risk of bias in duplicate with a pre-tested form. We conducted random-effects meta-analysis and Bayesian network meta-analysis. We included 52 studies of duration 5 years or less with 1 108 541 children, and four long-term studies 8-10 years after mass deworming programmes with more than 160 000 children. Overall risk of bias was moderate. Mass deworming for soil-transmitted helminths compared with controls led to little to no improvement in weight over a period of about 12 months (0·99 kg, 95% credible interval [CrI] -0·09 to 0·28; moderate certainty evidence) or height (0·07 cm, 95% CrI -0·10 to 0·24; moderate certainty evidence), little to no difference in proportion stunted (eight fewer per 1000 children, 95% CrI -48 to 32; high certainty evidence), cognition measured by short-term attention (-0·23 points on a 100 point scale, 95% CI -0·56 to 0·14; high certainty evidence), school attendance (1% higher, 95% CI -1 to 3; high certainty evidence), or mortality (one fewer per 1000 children, 95% CI -3 to 1; high certainty evidence). We found no data on quality of life and little evidence of adverse effects. Mass deworming for schistosomiasis might slightly increase weight (0·41 kg, 95% CrI -0·20 to 0·91) and has little to no effect on height (low certainty evidence) and cognition (moderate certainty evidence). Our analyses do not suggest indirect benefits for untreated children from being exposed to treated children in the community. We are uncertain about effects on long-term economic productivity (hours worked), cognition, literacy, and school enrolment owing to very low certainty evidence. Results were consistent across sensitivity and subgroup analyses by age, worm prevalence, baseline nutritional status, infection status, impact on worms, infection intensity, types of worms (ascaris, hookworm, or trichuris), risk of bias, cluster versus individual trials, compliance, and attrition. Mass deworming for soil-transmitted helminths with or without deworming for schistosomiasis had little effect. For schistosomiasis, mass deworming might be effective for weight but is probably ineffective for height, cognition, and attendance. Future research should assess which subset of children do benefit from mass deworming, if any, using individual participant data meta-analysis. Canadian Institutes of Health Research and WHO.

Role of honey after tonsillectomy: a systematic review and meta-analysis of randomised controlled trials.

Honey reduced post-tonsillectomy pain, but its effects on awakening at night, inflammation and healing of the tonsillar fossa were controversial. This systematic review and meta-analysis of randomised controlled trials (RCTs) evaluated the effect of oral honey on pain, consumption of painkillers, awakening at night, healing of tonsillar fossa and adverse effects in children after tonsillectomy. A search of MEDLINE, EMBASE, Scopus, CINAHL and Cochrane Collaboration Library databases was performed without any restriction of publication year. The end date of search was 30 June 2016. The search was supplemented by search from Google, hand search of cross-references of selected articles and reviews, and contacting the authors of different studies. The inclusion criteria were RCTs comparing the effect of honey with control on different outcomes, in children after tonsillectomy. Our search generated 64 studies, and eight RCTs met our inclusion criteria. The methodological quality of RCTs was poor. Compared to control, honey significantly decreased postoperative pain from day 1 to day 7 (P = 0.05 to <0.0001); consumption of painkillers from days 1 to 5 (P = 0.03 to 0.003) and on day 10 (P = 0.002); and number of awakening at night due to pain on days 2 and 4 after tonsillectomy (P = 0.0001, 0.004). The healing of tonsillar fossa was significantly greater with honey compared to control on days 3-4 (P = 0.02) and days ≥9 (P = 0.01) after tonsillectomy. The adverse effects were not significantly different between honey and control groups. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) of the evidence for different outcomes varied from 'low' to 'very low'. Honey improved pain, requirement of painkillers and awakening at night due to pain in children after tonsillectomy. There was little improvement in healing of tonsillar fossa. The GRADE of the evidence varied from 'low' to 'very low'. A good-quality, placebo-controlled RCT of different doses and durations of administration of honey is required to evaluate its clear efficacy and safety in children after tonsillectomy.

Intravenous Colistin Use for Multidrug-Resistant Gram-Negative Infections in Pediatric Patients.

The emergence of infections due to multidrug-resistant Gram-negative bacilli (MDR-GNB) has led to the resurrection of colistin use. The data on colistin use and drug-related adverse effects in children are scarce. In this study, we aimed to evaluate the clinical efficacy and safety of colistin use in critically ill pediatric patients. This study has a retrospective study design. Sixty-one critically ill children were identified through the department's patient files archive during the period from January 2011 to November 2014. Twenty-nine females and thirty-two males with a mean±standard deviation (SD) age of 61±9 months (range 0-216, median 12 months) received IV colistin due to MDR-GNB infections. Bacteremia (n=23, 37.7%) was the leading diagnosis, followed by pneumonia (n=19, 31%), clinical sepsis (n=7, 11.4%), wound infection (n=6, 9.8%), urinary tract infection (n=5, 8.1%) and meningitis (n=1, 1.6%). All of the isolates were resistant to carbapenems; however, all were susceptible to colistin. The isolated microorganisms in decreasing order of frequency were: Acinetobacter baumanni (n=27, 44.2%), Pseudomonas aeruginosa (n=17, 27.8%), Klebsiella pneumoniae (n=6, 9.8%), K. pneumoniae and Stenotrophomonas maltophilia (n=1, 1.6%), K. pneumoniae and A. baumanni (n=1, 1.6%), K. oxytoca (n=1, 1.6%) and Enterobacter cloacae (n=1, 1.6%). In seven patients, no microorganisms were detected; however, five of these patients were colonized by carbapenem-resistant K. pneumoniae. The mean duration of colistin therapy was 12 days (range 3-45). Colistin was administered concomitantly with one of the following antibiotics: carbapenem (n=50, %82), ampicillin-sulbactam (n=5, 8%), quinolones (n=5, 8%), rifampicin (n=1, 1.6%). Carbapenem was the most frequently used antibiotic. Nephrotoxicity was observed in only 1 patient, and we did not observe neurotoxicity in this study. All the patients received intravenous colistin (colisthimethate) at a dosage of 5 mg/kg daily by dividing it in three equal doses. Seven (11.4%) patients died during the study period. Colistin appears to be a safe and efficacious drug for treating MDR-GNB infections in children.

Serum Concentration of Risperidone and Adverse Effects in Children and Adolescents

Serum Concentration of Risperidone and Adverse Effects in Children and Adolescents

1.0 Psychopharmacology Update: Focus on Refractory Cases and Longer-Term Outcomes

At an increasing rate, children and adolescents are presenting for psychopharmacological treatment. Among these youth, a number are either comorbid or refractory to traditional treatments. Furthermore, longer-term outcomes of pharmacological treatments on the course and adverse effects in children remain of concern.

Hydrocortisone as an Intervention for Dexamethasone-Induced Adverse Effects in Pediatric Patients With Acute Lymphoblastic Leukemia: Results of a Double-Blind, Randomized Controlled Trial.

Dexamethasone is a key component in the treatment of pediatric acute lymphoblastic leukemia (ALL), but can induce serious adverse effects. Recent studies have led to the hypothesis that neuropsychological adverse effects may be a result of cortisol depletion of the cerebral mineralocorticoid receptors. We examined whether including a physiologic dose of hydrocortisone in dexamethasone treatment can reduce neuropsychologic and metabolic adverse effects in children with ALL. We performed a multicenter, double-blind, randomized controlled trial with a crossover design. Of 116 potentially eligible patients (age 3 to 16 years), 50 were enrolled and were treated with two consecutive courses of dexamethasone in accordance with Dutch Childhood Oncology Group ALL protocols. Patients were randomly assigned to receive either hydrocortisone or placebo in a circadian rhythm (10 mg/m(2)/d) during both dexamethasone courses. Primary outcome measure was parent-reported Strength and Difficulties Questionnaire in Dutch, which assesses psychosocial problems. Other end points included questionnaires, neuropsychological tests, and metabolic parameters. Of 48 patients who completed both courses, hydrocortisone had no significant effect on outcome; however, a more detailed analysis revealed that in 16 patients who developed clinically relevant psychosocial adverse effects, addition of hydrocortisone substantially reduced their Strength and Difficulties Questionnaire in Dutch scores in the following domains: total difficulties, emotional symptoms, conduct problems, and impact of difficulties. Moreover, in nine patients who developed clinically relevant, sleep-related difficulties, addition of hydrocortisone reduced total sleeping problems and disorders of initiating and maintaining sleep. In contrast, hydrocortisone had no effect on metabolic parameters. Our results suggest that adding a physiologic dose of hydrocortisone to dexamethasone treatment can reduce the occurrence of serious neuropsychological adverse effects and sleep-related difficulties in pediatric patients with ALL.

Very early discharge versus early discharge versus non-early discharge in children with cancer and febrile neutropenia.

Chemotherapy-induced neutropenia is a common adverse effect in children with cancer. Due to the high relative risk of infections and infectious complications, standard care for children with cancer and febrile neutropenia consists of routine hospitalization and parenteral administration of broad-spectrum antibiotics. However, there are less serious causes of febrile neutropenia; in a subgroup of these children, lengthy in-hospital treatment might be unnecessary. Various research groups have studied the adjustment of standard care to shorten in-hospital treatment for children with cancer and febrile neutropenia at low risk for bacterial infections. However, most of these studies were not done in a randomized matter. To evaluate whether early discharge (mean/median of less than five days) from in-hospital treatment was not inferior to non-early discharge (mean/median of five days or more) and whether very early discharge (mean/median of less than 24 hours) was not inferior to early discharge, non-early discharge, or a combination of these, in children with cancer and febrile neutropenia. We searched the Cochrane Central Register of Controlled Trials (2015, issue 11), MEDLINE/PubMed (from 1945 to December 2015), EMBASE/Ovid (from 1980 to December 2015), the reference lists of relevant articles and review articles, and various conference proceedings (dependent on availability from 2005 to 2010 to 2013 to 2015). We scanned the International Standard Randomised Controlled Trials Number (ISRCTN) Register, the National Institute of Health Register for ongoing trials, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 9 January 2016. We included all randomized controlled trials and controlled clinical trials in which children with cancer and febrile neutropenia were divided in groups with different times of discharge. We used standard methods of Cochrane and its Childhood Cancer Group. Two independent review authors performed study selection, data extraction, and risk of bias assessment. We entered data extracted from the included studies into Review Manager 5 and undertook analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. We included two randomized controlled trials assessing very early, early, non-early (or a combination of these) discharge in children with cancer and febrile neutropenia. We graded the evidence as low quality; we downgraded for risk of bias and imprecision. One study, Santolaya 2004, consisted of 149 randomized low-risk episodes and compared early discharge (mean/median of less than five days) to non-early discharge (mean/median of five days or more). This study found no clear evidence of difference in treatment failure (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.24 to 3.50, P value = 0.89 for rehospitalization or adjustment of antimicrobial treatment, or both; Fischer's exact P value = 0.477 for death) or duration of treatment (mean difference -0.3 days, 95% CI -1.22 to 0.62, P value = 0.52 for any antimicrobial treatment; mean difference -0.5 days, 95% CI -1.36 to 0.36, P value = 0.25 for intravenous antimicrobial treatment; mean difference 0.2 days, 95% CI -0.51 to 0.91, P value = 0.58 for oral antimicrobial treatment). Costs were lower in the early discharge group (mean difference USD -265, 95% CI USD -403.14 to USD -126.86, P value = 0.0002). The second included study, Brack 2012, consisted of 62 randomized low-risk episodes and compared very early discharge (mean/median of less than 24 hours) to early discharge (mean/median of less than five days). This study also found no clear evidence of difference in treatment failure (RR 0.54, 95% CI 0.15 to 1.89, P value = 0.34 for rehospitalization or adjustment of antimicrobial treatment (or both); Fischer's exact P value = 0.557 for death). Regarding duration of treatment, median duration of intravenous antimicrobial treatment was shorter in the very early discharge group (Wilcoxon's P value ≤ 0.001, stated in the study) and median duration of oral antimicrobial treatment was shorter in the early discharge group (Wilcoxon's P ≤ 0.001, stated in the study) as compared to one another. However, there was no clear evidence of difference in median duration of any antimicrobial treatment (Wilcoxon's P value = 0.34, stated in the study). Costs were not assessed in this study. Neither of the included studies assessed quality of life. Meta-analysis was not possible as the included studies assessed different discharge moments and used different risk stratification models. Very limited data were available regarding the safety of early discharge compared to non-early discharge from in-hospital treatment in children with cancer and febrile neutropenia and a low risk for invasive infection. The absence of clear evidence of differences in both studies could be due to lack of power.Evidently, there are still profound gaps regarding very early and early discharge in children with cancer and febrile neutropenia. Future studies that assess this subject should have a large sample size and aim to establish uniform and objective criteria regarding the identification of a low-risk febrile neutropenic episode.

Deworming and adjuvant interventions for improving the developmental health and well‐being of children in low‐ and middle‐income countries: a systematic review and network meta‐analysis

Deworming and adjuvant interventions for improving the developmental health and well‐being of children in low‐ and middle‐income countries: a systematic review and network meta‐analysis

Recent Epidemiological Studies on Methylmercury, Mercury and Selenium.

More than sixty years has passed since the outbreak of Minamata disease, and high-level methylmercury contaminations now seem nonexistent in Japan. However, mercury has been continuously discharged from natural sources and industrial activities, and the health effects on children susceptible to methylmercury exposure at low levels, in addition to mercury contamination from mercury or gold mining areas in developing countries, become a worldwide concern. In this article, we provide a recent overview of epidemiological studies regarding methylmercury and mercury. The following findings were obtained. (1) Many papers on exposure assessment of methylmercury/mercury have been published since the Minamata Convention on Mercury was adopted in 2013. (2) The most crucial problem is child developmental neurotoxicity resulting from prenatal exposure to methylmercury, but its precise assessment seems to be difficult because most of such effects are neither severe nor specific. (3) Several problems raised in birth cohort studies (e.g., whether IQ deficits due to prenatal methylmercury exposure remain when the children become adults, or whether the postnatal exposure at low levels also causes such adverse effects in children) remain unsolved. (4) Concurrent exposure models of methylmercury, lead, polychlorinated biphenyls, aresenic, and organochlorine pesticides, as well as possible antagonists such as polyunsaturated fatty acids and selenium, should be considered in the study design because the exposure levels of methylmercury are extremely low in developed countries. (5) Further animal experiments and molecular biological studies, in addition to human studies, are required to clarify the mechanism of methylmercury toxicity.

Dexmedetomidine as an adjuvant to bupivacaine in caudal analgesia in children

Context:Postoperative pain management is becoming an integral part of anesthesia care. Various techniques of pediatric pain relief have been designed among which the most commonly practiced is caudal epidural block. Several adjuvants have been used to prolong the duration of caudal analgesia such as clonidine, neostigmine, ketamine, opioids, and ephedrine. We have designed the study using dexmedetomidine as an adjuvant to assess analgesic efficacy, duration of postoperative analgesia, hemodynamic stability, postoperative sedation, and any adverse effects in children.Aims:The aim is to study the effects of dexmedetomidine as an adjuvant to bupivacaine in caudal analgesia in pediatric patients posted for infraumbilical surgeries.Settings and Design:This is a randomized, double-blind study in which effect of dexmedetomidine is studied when added to bupivacaine in the caudal epidural block. The observations are made intraoperatively for hemodynamic stability and postoperatively for the duration of analgesia.Subjects and Methods:This study was conducted in 100 children of American Society of Anesthesiologists physical status I and II, aged 2–10 years, undergoing elective infraumbilical surgeries. They were divided into two groups as follows: Group A: (0.25%) bupivacaine 1 ml/kg + normal saline (NS) 1 ml. Group B: (0.25%) bupivacaine 1 ml/kg + 1 μg/kg dexmedetomidine in 1 ml NS. As this study was double-blind, patients were randomly assigned to receive either (bupivacaine + saline) or (bupivacaine + dexmedetomidine) in each group. The patients were observed for hemodynamic stability, respiratory depression, and postoperative pain using face, legs, activity, cry, consolability (FLACC) pain scale for 24 h postoperatively.Statistical Analysis Used:Unpaired Student's t-test.Results:The mean duration of effective analgesia in Group A patients was 4.33 ± 0.98 h versus 9.88 ± 0.90 h in Group B patients. Likewise, the difference in mean FLACC score of both the groups was also statistically significant, 7.21 ± 0.76 and 6.49 ± 1.72 in Group A and Group B, respectively.Conclusion:Dexmedetomidine as adjuvant to Bupivacaine increases duration of caudal analgesia and improves hemodynamic stability without an increase in adverse effects in children undergoing infraumbilical surgeries.

Zinc Therapy for Wilson Disease in Children in French Pediatric Centers

Zinc therapy is considered a good option in Wilson disease (WD), as a first-line treatment in presymptomatic children and a maintenance therapy after the initial chelator therapy. The aim of the study was to determine the practical use of zinc treatment in French pediatric centers. A national survey was conducted in the 6 French centers using zinc acetate to treat WD. Clinical and biological parameters, dosage, and outcome were recorded. A total of 26 children were reported to be treated with zinc acetate, alone or in association with chelators. Of the 9 children (35%) who received zinc alone as a first-line therapy, 2 were switched to D-penicillamine because of inefficacy and 7 remained on zinc alone, but serum transaminase levels normalized in only 4 of them. Five children (19%) were initially treated with zinc in association with D-penicillamine (n = 4) or Trientine (n = 1) with good efficacy. Among the 12 children (46%) who received zinc as a maintenance therapy after D-penicillamine, no relapse of hepatic cytolysis occurred during a median follow-up of 5.2 years, but 2 of them were switched to Trientine because of zinc-related adverse effects. Epigastric pain was observed in 4 children, and a gastric perforation occurred in 1 child. The present study demonstrates poor efficacy of zinc as first-line therapy to control liver disease in half presymptomatic children and a high incidence of related gastrointestinal adverse effects in children with WD.

The Effect of Deworming on Growth in One-Year-Old Children Living in a Soil-Transmitted Helminth-Endemic Area of Peru: A Randomized Controlled Trial.

BackgroundAppropriate health and nutrition interventions to prevent long-term adverse effects in children are necessary before two years of age. One such intervention may include population-based deworming, recommended as of 12 months of age by the World Health Organization in soil-transmitted helminth (STH)-endemic areas; however, the benefit of deworming has been understudied in early preschool-age children.Methodology/Principal FindingsA randomized, double-blind, placebo-controlled trial was conducted to determine the effect of deworming (500 mg single-dose crushed mebendazole tablet) on growth in one-year-old children in Iquitos, Peru. Children were enrolled during their routine 12-month growth and development clinic visit and followed up at their 18 and 24-month visits. Children were randomly allocated to: Group 1: deworming at 12 months and placebo at 18 months; Group 2: placebo at 12 months and deworming at 18 months; Group 3: deworming at both 12 and 18 months; or Group 4: placebo at both 12 and 18 months (i.e. control group). The primary outcome was weight gain at the 24-month visit. An intention-to-treat approach was used. A total of 1760 children were enrolled between September 2011 and June 2012. Follow-up of 1563 children (88.8%) was completed by July 2013. STH infection was of low prevalence and predominantly light intensity in the study population. All groups gained between 1.93 and 2.05 kg on average over 12 months; the average difference in weight gain (kg) compared to placebo was: 0.05 (95% CI: -0.05, 0.17) in Group 1; -0.07 (95%CI: -0.17, 0.04) in Group 2; and 0.04 (95%CI: -0.06, 0.14) in Group 3. There was no statistically significant difference in weight gain in any of the deworming intervention groups compared to the control group.ConclusionsOverall, with one year of follow-up, no effect of deworming on growth could be detected in this population of preschool-age children. Low baseline STH prevalence and intensity and/or access to deworming drugs outside of the trial may have diluted the potential effect of the intervention. Additional research is required to overcome these challenges and to contribute to strengthening the evidence base on deworming.Trial RegistrationClinicalTrials.gov (NCT01314937)

Opioid-related adverse effects in children undergoing surgery: unequal burden on younger girls with higher doses of opioids.

Unpredictable interindividual variability in response to opioids results in inadequate analgesia and opioid-related adverse effects. The effects of the child's sex on opioid response have not been well studied. The aim of this study is to determine the effects of sex on opioid-related adverse effects in children undergoing tonsillectomy. Prospective observational clinical study. Outpatient pediatric surgery. Two hundred and seventy five children between 6 and 15 years of age undergoing outpatient tonsillectomy. All children received standard perioperative care with a standard intraoperative dose of morphine. Opioid-related analgesia and safety outcomes included incidences of respiratory depression (RD), postoperative nausea and vomiting (PONV) and incidence of prolonged stay in the, post-anesthesia recovery unit (PACU) due to opioid related adverse effects. Given the small sample of minority population, we focused our study on 219 white children. Significant morphine effect was observed in girls but not boys for PONV (P = 0.001) and prolonged PACU stay due to PONV (P = 0.010). Although the overall incidence of RD is not statistically different between boys and girls, the incidence of RD (52% vs 32%) and PONV (43% vs 4%) tended to be more in white girls than boys as the total perioperative morphine dose increased to 0.3 mg/kg or more. This study demonstrates that child's sex influences morphine's dose response and adverse effects. White girls have an unequal burden with higher incidences of PONV, RD, and prolonged PACU stays following tonsillectomy from PONV and RD as total morphine doses are increased.

Cannabinoids for paediatric epilepsy: Weeding out the issues.

Cannabinoids for paediatric epilepsy: Weeding out the issues.

Novel Neuroimaging Methods to Understand How HIV Affects the Brain.

In much of the developed world, the HIV epidemic has largely been controlled by antiretroviral treatment. Even so, there is growing concern that HIV-infected individuals may be at risk for accelerated brain aging and a range of cognitive impairments. What promotes or resists these changes is largely unknown. There is also interest in discovering factors that promote resilience to HIV and combat its adverse effects in children. Here, we review recent developments in brain imaging that reveal how the virus affects the brain. We relate these brain changes to changes in blood markers, cognitive function, and other patient outcomes or symptoms, such as apathy or neuropathic pain. We focus on new and emerging techniques, including new variants of brain MRI. Diffusion tensor imaging, for example, can map the brain's structural connections, while fMRI can uncover functional connections. Finally, we suggest how large-scale global research alliances, such as ENIGMA, may resolve controversies over effects where evidence is now lacking. These efforts pool scans from tens of thousands of individuals and offer a source of power not previously imaginable for brain imaging studies.

Potential of casein as a nutrient intervention to alleviate lead (Pb) acetate-mediated oxidative stress and neurotoxicity: First evidence in Drosophila melanogaster

Understanding the interaction between dietary protein deficits and neurotoxicants such as lead (Pb) is critical since oxidative stress is a common denominator under such conditions. The Drosophila system is an extensively used model to investigate the interaction between nutrients and environmental toxicants. Accordingly, we have examined the hypothesis that casein (CSN) enrichment has the propensity to attenuate Pb-associated phenotype, oxidative stress and neurotoxicity in Drosophila melanogaster. Exposure of young (2–3 d) and adult flies (10–12 d old) to Pb acetate (0–20mM, 7 d) in the medium resulted in a concentration dependent mortality and the survivors exhibited a hyperactive phenotype. While males showed higher susceptibility to Pb among both age groups, young flies were relatively more susceptible than adults. Pb exposure (5–10mM, 5 d) among young flies caused robust oxidative stress as evidenced by markedly elevated levels of reactive oxygen species with concomitant perturbations in the activities of antioxidant enzymes (diminished SOD and elevated thioredoxin reductase) and altered redox state. Further, Pb caused significant elevation in the activity of acetylcholinesterase and dopamine levels. In a satellite study, we assessed the modulatory effect of CSN-enriched diet (1–2%) on Pb intoxication in terms of lethality, hyperactivity, oxidative stress and neurotoxicity. CSN markedly offset Pb-induced lethality and diminished the hyperactivity response. While CSN enrichment among Pb (5mM) treated flies caused further elevation in ROS levels and thioredoxin reductase activity, the SOD levels were restored to normalcy. Further, CSN improved the activity levels of complex I–III and restored the dopamine levels. Our data suggest that Pb-induced toxicity in the Drosophila system may be predominantly mediated through oxidative stress mechanisms and the propensity of casein-enriched diet to abrogate such responses. Hence, we propose that enrichment of diet with protein such as casein may be a useful approach to alleviate Pb associated adverse effects in children.

PO-0913 A Review Of Cuffed Vs. Uncuffed Endotracheal Tubes In Children

Background and aims The use of cuffed endotracheal tubes in paediatric patients is still a controversial topic. This paper aims to investigate whether cuffed or uncuffed tubes should be used in children under the age of 8 based on the literature that is currently available on this topic. Currently there are no guidelines on this topic. Methods literature review. Results The results of the first four studies reviewed all show significant results in favour of use of a cuffed endotracheal tube and a change in current practice. None of the studies reviewed showed that patients were more likely to suffer injury as a result of using a cuffed tube. This is important as the review covers a variety of patients including those undergoing elective operations, burn patients and those who are critically ill. All of the studies reviewed demonstrated potential benefits of introducing cuffed tubes into practice as they reduced exchange rate, air leaks and the costs associated with the anaesthetic gases used; without a significant increase in the rates of post-extubation stridor or failed extubation. Conclusion In conclusion cuffed tubes are shown to decrease the need for multiple intubations, reduce costs and are not shown to increase adverse effects in children of all ages.

Fluoxetine: juvenile pharmacokinetics in a nonhuman primate model

The selective serotonin reuptake inhibitor (SSRI) fluoxetine is the only psychopharmacological agent approved for use in children. While short-term studies of side effects have been performed, long-term consequences for brain development are not known. Such studies can be performed in appropriate animal models if doses modeling therapeutic use in children are known. The goal of this study was to identify a daily dose of fluoxetine in juvenile monkeys which would result in serum fluoxetine and norfluoxetine concentrations in the therapeutic range for children. Juvenile (2.5-year-old rhesus monkeys, n = 6) received single administration of doses of 1, 2, and 4mg/kgday fluoxetine on a background of chronic dosing at an intermediate level to provide steady-state conditions to model therapeutic administration. Using nonlinear modeling, standard pharmacokinetic parameters were derived. Cerebrospinal fluid monoamine neurotransmitters were assayed to confirm the pharmacological effects. Dose-dependent area under the curve (AUC) and C max values were seen, while T max and absorption/elimination half-lives were minimally influenced by dose. A dosage of 2mg/kgday given over a 14-week period led to steady-state serum concentrations of active agent (fluoxetine + norfluoxetine) similar to those recorded from drug monitoring studies in children. Cisternal cerebrospinal fluid concentrations of serotonin increased significantly over the 14-week period, while concentrations of the serotonin metabolite (5-HIAA) were lower but not significantly different. A dose of 2mg/kgday fluoxetine in juvenile rhesus monkeys provides an internal dose similar to therapeutic use in children and will help establish a valuable animal model for understanding fluoxetine's therapeutic and potential adverse effects in children.

G28(P) Tramadol intoxication: an emerging entity in paediatrics?

AimTramadol is a synthetic opioid widely used to treat pain in adults and children over 12 years old. Extensive research on the toxicity of tramadol in adults has been published...

The Effects of Single-Dose Rectal Midazolam Application on Postoperative Recovery, Sedation, and Analgesia in Children Given Caudal Anesthesia Plus Bupivacaine

Background. This study aimed to compare the effects of rectal midazolam addition after applying bupivacaine and caudal anesthesia on postoperative analgesia time, the need for additional analgesics, postoperative recovery, and sedation and to find out its adverse effects in children having lower abdominal surgery. Methods. 40 children between 2 and 10 years of ASA I-II were randomized, and they received caudal anesthesia under general anesthesia. Patients underwent the application of caudal block in addition to saline and 1 mL/kg bupivacaine 0.25%. In the postoperative period, Group C (n = 20) was given 5 mL saline, and Group M (n = 20) was given 0.30 mg/kg rectal midazolam diluted with 5 mL saline. Sedation scale and postoperative pain scale (CHIPPS) of the patients were evaluated. The patients were observed for their analgesic need, first analgesic time, and adverse effects for 24 hours. Results. Demographic and hemodynamic data of the two groups did not differ. Postoperative sedation scores in both groups were significantly lower compared with the preoperative period. There was no significant difference between the groups in terms of sedation and sufficient analgesia. Conclusions. We conclude that caudal anesthesia provided sufficient analgesia in peroperative and postoperative periods, and rectal midazolam addition did not create any differences. This trial is registered with ClinicalTrials.gov NCT02127489.