Adverse Events In Children Research Articles

Respiratory adverse events in children after IM ketamine

Respiratory adverse events in children after IM ketamine

Exhaled nitric oxide measurement before pediatric adenotonsillectomy: A feasibility study.

Exhaled nitric oxide (eNO) is a known biomarker for the diagnosis and monitoring of bronchial hyperreactivity in adults and children. To investigate the potential role of eNO measurement for predicting perioperative respiratory adverse events in children, we sought to determine its feasibility and acceptability before adenotonsillectomy. We attempted eNO testing in children, 4-12years of age, immediately prior to admission for outpatient adenotonsillectomy. We used correlations between eNO levels and postoperative adverse respiratory events to make sample size predictions for future studies that address the predictability of the device. One hundred and three (53%) of 192 children were able to provide an eNO sample. The success rate increased with age from 23% (9%-38%) at age 4 to over 85% (54%-98%) after age 9. Using the eNO normal value (<20ppb) as a cutoff, an expected sample size to detect a significant difference between children with and without adverse events is 868, assuming that respiratory adverse events occur in 29% of children. eNO testing on the day of surgery has limited feasibility in children younger than 7years of age. The most common reason for failure was inadequate physical performance while interacting with the testing device. The role of this respiratory biomarker in the context of perioperative outcomes for pediatric adenotonsillectomy remains unknown and should be further studied with improved technologies.

Serious adverse events in children with juvenile idiopathic arthritis and other rheumatic diseases on tocilizumab – a real-world experience

ObjectivesTo assess the incidence rate and type of serious adverse events (SAE) in children with rheumatic inflammatory diseases treated with the interleukin 6 blocker tocilizumab (TCZ). MethodsA retrospective review of all consecutive patients diagnosed with an inflammatory rheumatic disease and receiving at least one dose of TCZ was performed in two French tertiary pediatric rheumatology centers between 01/2007 and 06/2019. SAE were defined as a life-threatening event and/or an event requiring hospital admission, leading to permanent disability or treatment discontinuation. ResultsOne hundred four children (64 female) were included. Most children suffered from systemic (n = 43) or polyarticular-course juvenile idiopathic arthritis (n = 43). Median age at TCZ start was 8.9 years (IQR 4.7 – 12.1), most children had received prednisone (81%), and/or a biologic agent (84%) prior to TCZ. Median TCZ treatment duration was 1.6 years (IQR 0.5 – 2.7), total TCZ exposure 215 patient years. Thirty-three SAE were observed in 26 (25%) children (SAE 15.3/100 patient years), mostly infections and infusion reactions. Children with SAE were significantly younger at disease onset (p = 0.034) and TCZ initiation (p = 0.016). Children experiencing infusion reactions were more likely to have systemic JIA or another autoinflammatory disease (p = 0.021), they all had active disease. At last follow up, 61 (59%) children remained on TCZ. ConclusionIn this cohort, SAE and most commonly serious infections were observed in a quarter of children. Severe infusion reactions were associated with persistently active autoinflammatory disease. Ongoing careful monitoring of TCZ-treated patients, especially young children with marked systemic inflammation is required.

Probiotics for the prevention of antibiotic-associated adverse events in children-A scoping review to inform development of a core outcome set.

IntroductionRoutine use of probiotics during antibiotic therapy in children remains a subject of discussion. To facilitate synthesis of individual study results and guideline formulation, it is important to assess predefined, similar, and clinically important outcomes. Core outcome sets are a proposed solution for this issue. The aim of this review was to document choice, design, and heterogeneity of outcomes in studies that assessed the effects of probiotics used for the prevention of antibiotic-associated adverse events in children.MethodsA scoping literature search covering three major databases was performed. Studies that evaluated oral probiotics' use concomitant with antibiotic therapy in children were included. Data on outcome definitions, measurement instruments, and follow-up were extracted. The outcomes were assigned to predefined core areas and domains. Data were analyzed descriptively.ResultsThirty-seven studies were included in this review. Diarrhea, the most commonly reported outcome, had diagnostic criteria clearly defined only in 21 studies. In total, 16 different definitions of diarrhea were identified. Diarrhea duration, severity, and etiology were reported in 9, 4, and 7 studies, respectively. Twenty studies assessed gastrointestinal symptoms other than diarrhea. Seven studies reported outcomes related to resource use or the economic impact of the intervention. Only 2 studies assessed outcomes related to life impact. None of the studies predefined adverse events of probiotic use.ConclusionsIdentified outcomes were characterized by substantial heterogeneity. The majority of outcomes were not designed to evaluate endpoints of real-life relevance. Results from this review suggest the need for a new core outcome set consisting of outcomes important for decision-making.

MON-170 Real World Estimates of Adrenal Insufficiency Related Adverse Events in Children with Congenital Adrenal Hyperplasia: On Behalf of the I-CAH Consortium

Background Although congenital adrenal hyperplasia (CAH) is a rare condition, it is the commonest cause of early-onset primary adrenal insufficiency and places the patient at a life-long risk of sick day episodes (SDE) and adrenal crises (AC). Objective To investigate the epidemiology of SDE and AC in an international cohort of patients <18 yrs old with 21-OH deficiency CAH. Methods Multi-level logistic model analysis of data in the International CAH (I-CAH) registry (www.i-cah.org) to examine the clinical associations of SDE, AC, stress-dose days and hospitalisations. Results 518 patients (F, 53%) from 34 centres in 18 countries with a median number of cases per centre of 12 (IQR 1-26), had a total of 5388 reported visits with a median duration of follow-up per patient of 3.1 yrs (IQR 2.5-5.8). Of the 518 patients, 334 (64%) had ≥1 SDE; the median number of SDE per patient year per centre was 1.0 (IQR 0.4-2.2) and the median duration of SDE was 3.0 days (IQR 2.0-5.0). Children between 1-4 yrs and adolescents (15-18 yrs) had a greater risk of SDE [OR 2.02 (95%CI:1.60,2.56) and OR 1.64 (95%CI:1.34,2.02), respectively] and stress-dosing [OR 2.03 (95%CI:1.56,2.60) and OR 1.63 (95%CI:1.32,2.02), respectively] compared to children <1 yr old. Males were more likely to have a SDE [OR 1.40 (95%CI:1.13,1.73) and stress-dosing [OR 1.40 (95%CI:1.12,1.76) than females. An AC was reported in 4% of SDE (62/1544) with 92% of visits associated with hospital admission. Infectious illness was the most frequent associated event and was reported in 72% (1105/1544) of SDE and 47% (29/62) of AC. Males had a higher risk of AC compared to females [OR 1.03 (95%CI:1.03,1.03). Children with salt-wasting CAH were more likely to be hospitalised during a SDE, compared with those with simple-virilising CAH [OR 2.08 (95%CI:0.99,7.91)]. Children receiving glucocorticoid (GC) doses within the hydrocortisone (HC) equivalent dose (ED) of 10-15mg/m2/d were more likely to have SDE [OR 1.66 (95%CI:1.31,2.10), stress-dosing [OR 1.85 (95%CI:1.44,2.37) and AC [OR 1.08 (95%CI:1.08,1.08), p<0.001] than children on HC ED >15mg/m2/day. Similarly, children on HC ED <10mg/m2/d were more likely to have SDE [OR 2.20 (95%CI:1.66,2.90)], stress-dosing [OR 2.37 (95%CI:1.77,3.19)] and AC [OR 8.34 (95%CI:8.33,8.35), p<0.001] than those on higher doses. Children on FC doses between 50-200mcg/day and lower than 50 mcg were less likely to have AC [OR 4.54 (95%CI:4.54,4.55) and OR 8.58 (95%CI:8.57,8.59), respectively] than those on higher doses (>200mcg/day). Oral GC were increased in 74% (1147/1544) of SDE whilst HC injection was administered in 11% (176/1544) of SDE. Conclusions The real-world data within the I-CAH registry are a valuable resource for identifying factors that place a child with CAH at a higher risk of adverse events and can be used in prediction models for calculating individual risk.

Analysis of adverse events and influencing factors in randomized controlled trials of oral Chinese medicine published in English

In order to analyze the incidence of adverse events(AE) and evaluate the related influencing factors in randomized controlled trials(RCTs) of oral Chinese medicine which published in English, Medline, EMbase, and the Cochrane Central Register of Controlled Trials(CENTRAL) database were searched. Oral Chinese medicine RCTs published in English from January 2009 to July 2018 were collected to extract the basic characteristics, subjects, intervention characteristics and AE information. The AE incidence of each study was merged by using Meta analysis. Finally, 218 RCTs were included, of which 28.4% did not report any AE. A total of 1 634 AE occurred in 103 oral Chinese medicine groups, and the total incidence of AE was 11.2%(95%CI[10.7%, 11.7%]). The highest incidence of AE came to blood routine laboratory abnormalities, 8.0%(95%CI[6.6%, 9.7%]), followed by neurological and psychiatric systems 7.9%(95%CI[6.6%, 9.5%]), digestive system 7.8%(95%CI[6.8%, 8.9%]) and liver function abnormalities 7.6%(95%CI[6.4%, 8.9%]). Among the oral dosage forms, tablets and granules had the highest incidence of AEs, while decoction and oral liquids had the lowest incidence. The combination of oral Chinese medicine and Western medicine had the highest incidence of AE. As the medication course increased, the incidence of AE increased accordingly. The incidence of AE in children was higher than that in adults. Based on the analysis results, the higher AE incidence of oral Chinese medicine was in the neuropsychiatric system, gastrointestinal system and liver function abnormalities. The incidence of AE was related to the dosage form, drug combination, medication duration, and patient age. We should pay attention to the AE in children due to modern dosage forms of traditional Chinese medicine, combination of Chinese and Western medicine, and long course of medication.

EEG oscillation evidences of altered resting-state brain activity in children orphaned by parental HIV/AIDS

ABSTRACTEarly life adverse events in children orphaned by parental HIV/AIDS can have long-lasting effects on brain function. However, data are limited regarding the brain activation during resting state in these children. The current study aims to investigate the brain oscillation at rest in children orphaned by HIV/AIDS using resting-state EEG data. Data were derived from a larger neurodevelopmental study in which 90 children aged 9–17 years orphaned by AIDS and 66 matched controls were recruited through the local communities and school system. Children (63 orphans and 65 controls) who had resting-state EEG data and completed the Teacher-Child Rating Scale (T-CRS) were included in the current analysis. EEG results showed that children orphaned by HIV/AIDS had increased theta activity in the midline region, decreased beta activity in left hemisphere and overall increased theta/beta power ratio. Furthermore, the theta/beta ratio is positively correlated with learning problem and acting out scores, and negatively correlated with task orientation and peer social skill activities. Findings support that children orphaned by HIV/AIDS demonstrate different brain activity compared to non-orphan controls and also suggest that the EEG activities in resting state may serve as useful indicators of children’s behavioral problems.

Schistosomiasis and soil-transmitted helminthiasis preventive chemotherapy: Adverse events in children from 2 to 15 years in Bengo province, Angola.

Preventive chemotherapy campaigns with praziquantel and albendazole are being implemented in Angola, as a high priority public health intervention. However, there are no published data regarding adverse events associated with these medications. In this context, we analysed adverse events due to co-administration of praziquantel and albendazole in endemic areas of schistosomiasis and soil-transmitted helminths in Bengo, Angola. In the context of a targeted drug administration, between December 2012 and September 2013, we conducted two surveys after co-administrating single oral doses of praziquantel and albendazole tablets to children 2 to 15 years of age. About 24 hours after each treatment, participants answered a questionnaire about adverse events. At baseline, 605 children (55.0% male; mean age: 9.7 years) were treated; 460 were interviewed and 257 (55.9%) reported at least one adverse event, 62.3% (160/257) of children being infected with schistosoma haematobium. After six months of treatment, among 339 children surveyed, 184 (54.3%) reported adverse events, with 49.5% (91/184) of infected children. Adverse events were most common in preschool-aged children, with no significant difference between genders. The most frequent adverse events in the two surveys were abdominal pain (18.5%, 25.7%), headache (20.9%, 23.0%) and dizziness (15.7%, 19.8%). Children aged 12 to 15 years (adjusted OR = 0.40, p = 0.040) and those with mixed infection (adjusted OR = 0.04, p = 0.011) had lower odds of adverse events. After the second treatment, those with heavy infection (adjusted OR = 2.72, p = 0.018) and aged 9-11 years (adjusted OR = 2.01, p = 0.049) had significantly fewer adverse events. About 2.0% of children experienced severe adverse events. This study adds evidence that preventive chemotherapy for schistosomiasis and soil-transmitted helminths control is safe, but cases of adverse events are expected. Standardized methodologies to discriminate drug-related adverse events from the clinical manifestations of the infections are needed.

Airway management and perioperative adverse events in children with mucopolysaccharidoses and mucolipidoses: A retrospective cohort study.

Children suffering from mucopolysaccharidoses (subtypes I, II, III, IV, VI, and VII) or mucolipidoses often require anesthesia, but are at high risk for perioperative adverse events. However, the impact of the disease subtype and the standard of care for airway management are still unclear. This study aimed to assess independent risk factors for perioperative adverse events in individuals with mucopolysaccharidoses/mucolipidoses and to analyze the interaction with the primary airway technique implemented. This retrospective study included individuals with mucopolysaccharidoses/mucolipidoses who underwent anesthesia at two high-volume centers from 2002 to 2016. The data were analyzed in a multivariate hierarchical model, accounting for repeated anesthesia procedures within the same patient and for multiple events within a single anesthesia. Of 141 identified inpatients, 67 (63 mucopolysaccharidoses and 4 mucolipidoses) underwent 269 anesthesia procedures (study cases) for 353 surgical or diagnostic interventions. At least one perioperative adverse event occurred in 25.6% of the cases. The risk for perioperative adverse events was higher in mucopolysaccharidoses type I (OR 8.0 [1.5-42.7]; P=.014) or type II (OR 8.8 [1.3-58.6]; P=.025) than in type III. Fiberoptic intubation through a supraglottic airway was associated with the lowest risk for perioperative adverse events and lowest conversion rate. Direct laryngoscopy was associated with a significantly higher risk for airway management problems than indirect techniques (estimated event rates 47.8% vs 10.1%, OR 24.05 [5.20-111.24]; P<.001). The risk for respiratory adverse events was significantly higher for supraglottic airway (22.6%; OR 31.53 [2.79-355.88]; P=.001) and direct laryngoscopy (14.8%; OR 14.70 [1.32-163.44]; P=.029) than for fiberoptic intubation through a supraglottic airway (2.1%). The disease subtype and primary airway technique were the most important independent risk factors for perioperative adverse events. Our findings indicate that in MPS/ML children with predicted difficult airway indirect techniques should be favored for the first tracheal intubation attempt.

Salbutamol administered preoperatively to children undergoing tonsillectomy resulted in a significant reduction in rates of respiratory adverse events

Review of Von Ungern-Sternberg BS, Sommerfield D, Slevin L, Drake-Brockman TFE, Zhang G, Hall GL. Effect of albuterol premedication vs placebo on the occurrence of respiratory adverse events in children...

Equivalent schedules of intradermal fractional dose versus intramuscular full dose of inactivated polio vaccine for prevention of poliomyelitis.

Poliomyelitis is a debilitating and deadly infection. Despite exponential growth in medical science, there is still no cure for the disease, which is caused by three types of wild polioviruses: types 1, 2, and 3. According to the Global Polio Eradication Initiative (GPEI), wild poliovirus is still in circulation in three countries, and fresh cases have been reported even in the year 2018. Due to the administration of live vaccines, the risk for vaccine-derived poliovirus (VDPV) is high in areas that are free from wild polioviruses. This is evident based on the fact that VDPV caused 20 outbreaks between 2000 and 2011. Recent recommendations from the World Health Organization favoured the inclusion of inactivated poliovirus vaccine (IPV) in the global immunisation schedule. IPV can be delivered in two ways: intramuscularly and intradermally. IPV was previously administered intramuscularly, but shortages in vaccine supplies, coupled with the higher costs of the vaccines, led to the innovation of delivering a fractional dose (one-fifth) of IPV intradermally. However, there is uncertainty regarding the efficacy, immunogenicity, and safety of an intradermal, fractional dose of IPV compared to an intramuscular, full dose of IPV. To compare the immunogenicity and efficacy of an inactivated poliovirus vaccine (IPV) in equivalent immunisation schedules using fractional-dose IPV given via the intradermal route versus full-dose IPV given via the intramuscular route. We searched CENTRAL, MEDLINE, Embase, 10 other databases, and two trial registers up to February 2019. We also searched the GPEI website and scanned the bibliographies of key studies and reviews in order to identify any additional published and unpublished trials in this area not captured by our electronic searches. Randomised controlled trials (RCTs) and quasi-RCTs of healthy individuals of any age who are eligible for immunisation with IPV, comparing intradermal fractional-dose (one-fifth) IPV to intramuscular full-dose IPV. We used standard methodological procedures expected by Cochrane. We included 13 RCTs involving a total of 7292 participants, both children (n = 6402) and adults (n = 890). Nine studies were conducted in middle-income countries, three studies in high-income countries, and only one study in a low-income country. Five studies did not report methods of randomisation, and one study failed to conceal the allocations. Eleven studies did not blind participants, and six studies did not blind outcome assessments. Two studies had high attrition rates, and one study selectively reported the results. Three studies were funded by pharmaceutical companies. Paralytic poliomyelitis. No study reported data on this outcome. Seroconversion rates. These were significantly higher for all three types of wild poliovirus for children given intramuscular full-dose IPV after a single primary dose and two primary doses, but only significantly higher for type two wild poliovirus given intramuscularly after three primary doses: • dose one (six studies): poliovirus type 1 (odds ratio (OR) 0.30, 95% confidence interval (CI) 0.22 to 0.41; 2570 children); poliovirus type 2 (OR 0.43, 95% CI 0.31 to 0.60; 2567 children); poliovirus type 3 (OR 0.19, 95% CI 0.12 to 0.30; 2571 children); • dose two (three studies): poliovirus type 1 (OR 0.23, 95% CI 0.16 to 0.33; 981 children); poliovirus type 2 (OR 0.41, 95% CI 0.28 to 0.60; 853 children); and poliovirus type 3 (OR 0.12, 95% CI 0.07 to 0.22; 855 children); and • dose three (three studies): poliovirus type 1 (OR 0.45, 95% CI 0.07 to 3.15; 973 children); poliovirus type 2 (OR 0.34, 95% CI 0.19 to 0.63; 973 children); and poliovirus type 3 (OR 0.18, 95% CI 0.01 to 2.58; 973 children). Using the GRADE approach, we rated the certainty of the evidence as low or very low for seroconversion rate (after a single, two, or three primary doses) for all three poliovirus types due to significant risk of bias, heterogeneity, and indirectness in applicability/generalisability. Geometric mean titres. No study reported mean antibody titres. Median antibody titres were higher for intramuscular full-dose IPV (7 studies with 4887 children); although these studies also reported a rise in antibody titres in the intradermal group, none reported the duration for which the titres remained high. Any vaccine-related adverse event. Five studies (2217 children) reported more adverse events, such as fever and redness, in the intradermal group, whilst two studies (1904 children) reported more adverse events in the intramuscular group. There is low- and very low-certainty evidence that intramuscular full-dose IPV may result in a slight increase in seroconversion rates for all three types of wild poliovirus, compared with intradermal fractional-dose IPV. We are uncertain whether intradermal fractional-dose (one-fifth) IPV has better protective effects and causes fewer adverse events in children than intramuscular full-dose IPV.

Results from the Adverse Event Sedation Reporting Tool: A Global Anthology of 7952 Records Derived from >160,000 Procedural Sedation Encounters.

Background: The incidence of sedation-related adverse events, inclusive of both adults and children, administered by multiple specialty providers from different countries and venues, using standardized definitions, has never been reported on an international level. We are reporting the outcome data of the adverse event sedation reporting tool as an important step toward a more complete risk assessment of sedation-related morbidity, mortality, and etiology. The analysis of the AE sedation reporting data include descriptive measures to evaluate the characteristics of the provider, the patient, sedations performed, adverse events, interventions, and outcomes. The primary outcome was the rate and nature of adverse events. Between 12/14/2010 and 12/11/2018 there were 7952 sedations, from an estimated total of 164,114 sedations administered, of which 622 were reported as adverse events. The mean age of the entire patient population is 33.0 years (0.02–98.7). The providers represented 39 countries across six continents. Oxygen desaturation (75%–90%) for <60 s is the most prevalent adverse event with a rate of 7.8 per 10,000, followed by airway obstruction at a rate of 5.42 per 10,000. Apnea occurred at a rate of 4.75 per 10,000. Significant predictors of adverse events are ≥ ASA score III (p = 0.0003), procedure time (6:00 pm–12:00 am: p < 0.0001, 12:00–6:00 am: p = 0.0003), and non-hospital location (p < 0.0001). The AE sedation reporting tool has demonstrated that the majority of adverse events in children and adults who receive procedural sedation from multi-specialists internationally required minor interventions and had outcomes of minor risk.

Transient Elevations in Markers of Hepatic Function during Pediatric Acute Lymphoblastic Leukemia Treatment Are Common but Do Not Influence Outcomes: A Study of 805 Patients from the Learn Consortium

Introduction: Hepatotoxicity is a frequent and challenging adverse event in children with acute lymphoblastic leukemia (ALL), but patient factors that are predictive of hepatotoxicity are not well understood. We leveraged a data repository jointly developed by two pediatric oncology centers within the Leukemia Electronic Abstraction of Records [LEARN] Consortium to assess the landscape and determinants of liver dysfunction throughout ALL therapy in patients who were risk-stratified to receive either standard- or high-intensity treatment blocks. Methods: The subjects were children ages 1-21 years who were treated for ALL between 2006-2014 at either Children's Hospital of Philadelphia or Texas Children's Hospital. Demographics, disease-related data, and every laboratory value collected during treatment were obtained by targeted manual abstraction and extensive semi-automated extraction of patient electronic medical record (EMR) data. To reduce cohort heterogeneity, we excluded patients who received non-standard ALL therapies. Patients were categorized as receiving either standard-intensity or high-intensity treatment for their first three blocks of therapy (Induction, Consolidation, Interim Maintenance 1 [IM1]) based on chemotherapeutic agents delivered in those blocks. Differences in laboratory value-determined hepatoxicity were then analyzed based on this categorization for all remaining phases of therapy. Hepatic lab values (AST [SGOT], ALT [SGPT], total bilirubin [t. bili], and conjugated bilirubin [c. bili]) were first normalized to the age-based upper limit of normal (ULN), and the median value was then determined. A multivariate mixed-effects linear regression model with random effects was used to identify differences in the treatment group medians and the following covariates: age, race/ethnicity, sex, BMI, and ALL immunophenotype. Laboratory values were classified by the CTCAE v5.0 grading system, with grade ≥ 3 considered 'elevated.' Results: 805 pediatric ALL patients were included in the analysis, representing 114,095 hepatic lab values (Table 1). Less than 10% of patients had elevated lab values at diagnosis. Throughout treatment, the majority of lab values fell within 1-2x ULN for age for both standard- and high-intensity treatment groups (Fig. 1a-d). The median hepatic lab values for the high-intensity group were slightly higher than the standard risk group across all treatment phases, and this difference was most consistently significant in Consolidation and Delayed Intensification. Among the four hepatic labs that were assessed, ALT had the most significant deviation above normal (up to 30x ULN, Fig 1a). Patients were more likely to have elevated transaminases during maintenance than prior to maintenance (Fig. 1e). Similarly, but to a lesser degree, patients were more likely to have elevated t. or c. bili during maintenance than prior to maintenance. Age, race, and BMI were correlated with elevated hepatic labs, with Hispanic and/or overweight patients more likely to have elevations in 3 or more phases of therapy (Table 2). However, no hepatic lab abnormalities were correlated with either overall or relapse-free survival. Conclusions: This is the first comprehensive study of measures of hepatotoxicity in a large and uniformly-treated cohort of pediatric ALL. While significantly elevated hepatic labs are rare at diagnosis, they are common during ALL treatment and are seen more commonly in maintenance than in prior phases. Patients who are overweight and/or Hispanic are more likely to experience grade 3 or higher hepatoxicity. We observed no relationship between hepatotoxicity and relapse or survival. Further studies are ongoing to delineate the temporal correlation of liver function and chemotherapy dosing and administration. Disclosures No relevant conflicts of interest to declare.

Incidence of adverse events in antipsychotic-naïve children and adolescents treated with antipsychotic drugs: Results of a multicenter naturalistic study (ETAPE)

The main objective of ETAPE study was to determine the incidence of adverse events (AEs) potentially related to antipsychotic (AP) during a 12-months observational study of naturalistic treatment. ETAPE is a naturalistic prospective multicenter study conducted between April 2013 and May 2016. 200 patients were included. The mean age was 12 ± 3 years, with 73.6% being males. Patients presented a significant clinical improvement over time. At baseline, 92% of patients received a second generation AP, 74% AP monotherapy and 79.5% off-label AP prescriptions. Clinical diagnoses were heterogeneous including psychosis, anxiety, mood and neurodevelopmental disorders. The overall AE incidence rate was 11.52 AEs per person-years. Among AEs potentially attributable to AP, 15.4% were neuromotor, 14.8% gastroenterological, 12.2% metabolic and 11.8% general symptoms. Weight and body mass index increased significantly. More than half of AE appeared during the first 3 months, but onset of AE was noted all over follow-up. The presence of AEs was stable over time. ETAPE study highlights a high incidence rate of AE in children treated with AP. A careful and continuous clinical and biological monitoring is required to adapt treatment decisions based on benefice-risk-analysis. Moreover, additional research is warranted, also in regard of high proportion of off-label prescriptions.

892. Risk Factors for Adverse Events in Children Receiving Outpatient Antibiotic Therapy

BackgroundOutpatient parenteral antibiotic therapy (OPAT) can decrease the length of hospital stay but is associated with adverse events (AEs). The purpose of this study was to quantify and identify risk factors for OPAT-associated AEs in children.MethodsThis is a retrospective, single-center study of patients aged ≤21 years discharged on OPAT from January 2016 to April 2019. Only patients with OPAT overseen by the infectious disease service were included. Medication AE’s included: rash, neutropenia, hepatitis, diarrhea, C. difficile infection, increased serum creatinine, or others. Central line AEs included: central line dysfunction, infection, rash around line site, or other. Wilcoxon rank-sum test, Pearson’s χ2 test, Fisher’s exact test, and multivariable logistic regression models were used for analyses.ResultsDemographic information can be found in Table 1. Among 176 patients included in the study, an AE occurred in 69 (39%). In a multivariable logistic regression model adjusting for age, county of residence, duration of OPAT, and duration line was in place, each additional day of antibiotics increased the odds of having a medication or line-related AE by 3% (OR 1.03; 95% CI 1.01–1.06; P = 0.005; Table 2). Medication AEs occurred in 30 patients (17%). The most frequent medication AEs were neutropenia (24%), rash (15%), and increased liver function tests (15%). Patients residing in a Large Fringe Metro area (suburb) had 33% lower odds of having a drug-related AE compared with those in a Large Central Metro area (OR 0.67; 95% CI 0.50 to 0.90; P = 0.008). Line AEs occurred in 46 patients (26%), with 10 patients (21%) experiencing >1 line AE. The most common line AEs were line malfunction (56.5%) and line infection (13%). Seven patients experienced both a medication AE and a central line AE. Of the 176 patients, 20 (11%) were readmitted to the hospital due to medication or line AE and an additional 25 (14%) had a healthcare visit for an AE although did not require admission.ConclusionIn our region, nearly 40% of children experienced an OPAT-associated AE and line AEs were more common than medication AEs. Longer durations of IV therapy was an independent risk factor for AEs. Converting to oral antibiotic therapy as soon as feasible may reduce OPAT-associated AEs. DisclosuresRitu Banerjee, MD, PhD, Accelerate Diagnostics: Grant/Research Support; BioFire: Research Grant; Biomerieux: Research Grant; Roche: Research Grant.

Safety of longer linezolid regimen in children with drug-resistant tuberculosis and extensive tuberculosis in Southwest China

ObjectivesLinezolid (LNZ) has recently been listed by the World Health Organization (WHO) as a Group A agent for the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in longer regimens (18–20 months). However, little is known about the safety of LNZ in longer TB treatment regimens in children. MethodsHere we report 31 children who received LNZ treatment for drug-resistant tuberculosis (DR-TB) and extensive tuberculosis in the Children’s Hospital of Chongqing Medical University, China, during September 2016 to March 2019. The mean duration of LNZ treatment was 8.56 months (range, 1–24 months). ResultsOf the 31 patients, 13 (42%) had suspected or confirmed adverse events (AEs) related to LNZ treatment, including digestive symptoms, haematological toxicity, neuropathy and lactic acidosis. Haematological toxicity was the most frequent AE, presenting as leukopenia (9/13) and anaemia (5/13). No hepatotoxicity or nephrotoxicity was observed. Two patients suffered from life-threatening lactic acidosis when the LNZ dose was increased to 1.2 g daily, however they recovered following LNZ withdrawal. ConclusionA high rate of AEs of LNZ treatment was observed in children receiving a longer regimen, which might relate to the treatment course and dose. Haematological toxicity was the most frequent AE in children. It is necessary to regularly monitor the blood chemistry and lactic acid concentration during LNZ treatment.

Perioperative care of children with sickle cell disease: A systematic review and clinical recommendations.

Children with sickle cell disease (SCD) require specific perioperative care, and clinical practice in this area remains poorly defined. We aimed to conduct a systematic, PRISMA-based review of the literature, available clinical guidelines and practice recommendations. We also aimed to extract any valuable information for the "best of available-evidence"-based prevention of perioperative adverse events in children with SCD, and highlight the most urgent priorities in clinical research. As data sources, US National Library of Medicine, Medline, National Guideline Clearinghouse, International Guideline Network, TRIP databases were searched for any content until January 2019. We also included institutional, consortia and expert group guidelines. Included were reports/guidelines in English, French, German, and Italian. Excluded were reports on obstetrical and fetal management. We identified 202 reports/guidelines fulfilling the criteria outlined above. A majority focused on visceral, cardiovascular and orthopedic surgery procedures, and only five were multicenter randomized controlled trials and two prospective randomized studies. After grading of the quality of the evidence, the extracted data was summarized into clinical recommendations for daily practice. Additionally, we designed a risk-grading algorithm to identify contexts likely to be associated with adverse outcomes. In conclusion, we provide a systematic PRISMA-based review of the existing literature and ancillary practice and delineate a set of clinical recommendations and priorities for research.

Antibiotic adverse events in children with AOM

Antibiotic adverse events in children with AOM

Drug Dose Selection in Pediatric Obesity: Available Information for the Most Commonly Prescribed Drugs to Children.

Obesity rates continue to rise in children, and little guidance exists regarding the need for adjustment away from total body weight-based doses for those prescribing drugs to this population of children. A majority of drugs prescribed to children with obesity result in either sub-therapeutic or supra-therapeutic concentrations, placing these children at risk for treatment failure and drug toxicities. In this review, we highlight available obesity-specific pharmacokinetic and dosing information for the most frequently prescribed drugs to children in the inpatient and outpatient clinical settings. We also comment on available dosing recommendations for drugs prescribed to treat common pediatric obesity-related comorbidities. This review highlights that there is no safe or proven 'rule of thumb,' for dosing drugs for children with obesity, and a striking lack of pharmacokinetic data to support the creation of dosing guidelines for children with obesity for the most commonly prescribed drugs. It is important that those prescribing for children with obesity are aware of these gaps in knowledge and of potential drug treatment failure or adverse events related to drug toxicity as a result of these knowledge gaps. Until more data are available, we recommend close monitoring of drug response and adverse events in children with obesity receiving commonly prescribed drugs.

Infectious adverse events in children with Juvenile Idiopathic Arthritis treated with Biological Agents in a real-life setting: Data from the JIRcohorte.

The main objective of our study is to assess the infectious adverse events occurring in juvenile idiopathic arthritis (JIA) children treated with biological agents. Patients were selected from the retrospective module of the JIRcohorte, data concerning the period between January 2001 and August 2015. All infectious adverse events (IAE) were retrieved. For every infectious side effect, the date, the severity, the need for a hospitalization, the type of pathogen and the affected organ were noted. Incidence rates were expressed in number of events per 100 person-years (100p-y), and OR were calculated. Six hundred seventy-seven patients with JIA were included in the study. A total of 3075.4 person-years of exposure were analyzed. One hundred eighty-four infectious events were described (6.0 events/100 p-y): 15.5/100 p-y with tocilizumab (TCZ), 9.6/100 p-y with Canakinumab (CAN), 7.4/100 p-y with abatacept (ABA), 6.9/100 p-y with Golimumab (GOL), 6.7/100 p-y with Anakinra (ANA), 6.3/100 p-y with Infliximab, 4.8/100 p-y with Etanercept, and 3.7/100 p-y with Adalimumab. Risk of developing an infection was significantly higher with IL-6 antagonists or IL-1 antagonists than with TNF-inhibitor. Forty point eight percent of the infectious adverse events (IAE) affected the upper respiratory tract or the Ear, nose and throat (ENT) system. Twelve infectious adverse events were described as severe or very severe (0.4/100p-y). No case of tuberculosis or death was reported. Infectious complications with biologics occurring in children treated for JIA are rare, and in most of the cases have a mild or moderate severity, affecting mainly the upper respiratory tract or the ENT.