Trauma in pediatric populations.

Simple SummarySalivary gland tumors are rare among both pediatric and adult populations. Mucoepidermoid carcinoma (MEC) is a common type of malignant salivary gland tumor that presents with atypical clinical features. It is more commonly found in adults. Most commonly, MEC was less than 2 cm in size, moderately differentiated, and localized to the gland. Surgical resection was the most common treatment modality in both pediatric and adult populations (53.5%). The pediatric population with MEC had a lower death rate compared to the adult population. Tumor size greater than 2 cm, male sex, and distant spread were factors associated with a higher risk of death.Background: Salivary gland neoplasms are uncommon in both pediatric and adult populations. Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland tumors and usually presents with atypical clinical features. This study sought to evaluate the demographic and clinical factors affecting outcomes in adults and pediatric populations with MEC that could be used to risk stratification for treatment selection and clinical trial enrollment. Methods: Data on 4507 MEC patients were extracted from the Surveillance Epidemiology and End Result (SEER) database (2000–2018). Patients aged ≤ 18 years were classified into the pediatric population, and those older than 18 years were placed in the adult group. Kaplan–Meier survival curves were created to analyze survival probabilities for various independent factors. Results: The pediatric population comprised 3.7% of the entire cohort, with a predominance of females (51.5%), while the adult population constituted 96.3% of the cohort, with a predominance of female patients (52.2%). Caucasians were the predominant race overall (75.3%), while more African Americans were seen in the pediatric group. In tumor size of <2 cm overall, poorly differentiated tumors with higher metastasis rates were observed more in adults (11.3% and 9.3%) than in the pediatric population (3.0% and 4.8%, p < 0.05). Surgical resection was the most common treatment option (53.9%), making up 63.6% of the pediatric and 53.5% of the adult groups. A combination of surgical resection and radiation was used in 29.8% of the entire cohort while a combination of surgical resection, radiation, and chemotherapy made up only 3.2%. The pediatric group had a lower overall mortality rate (5.5%) than the adult group (28.6%). Females had a higher 5-year survival rate in comparison to males (86.5%, and 73.7%, respectively). Surgical resection led to a more prolonged overall survival and 5-year cancer-specific survival (98.4% (C.I, 93.7–99.6) in the pediatric group and 88.8% (C.I, 87.5–90.0) in the adult group), respectively. Metastasis to the lung, bone, brain, and/or liver was found to have significantly lower survival rates. Multivariate analysis demonstrated that adults (hazard ratio [HR] = 7.4), Asian or Pacific Islander (HR = 0.5), male (HR = 0.8), poorly differentiated histology (HR = 3.8), undifferentiated histology (HR = 4.5), regional spread (HR = 2.1), and distant spread (HR = 3.2) were associated with increased mortality (p < 0.05). Conclusions: Mucoepidermoid carcinoma of the salivary glands primarily affects Whites and is more aggressive in adults than in the pediatric population. Even with surgical resection, the overall survival is poor in the adult population as compared to its pediatric counterparts. Advanced age, larger tumor size, male sex, and lymph node invasion are associated with increased mortality.

The use of inhaled Nitric Oxide (iNO) in pediatric and adult cardiac centers: a Franco-Belgian multicenter prospective survey from the POSITIVE study group

e14024 Background: Choroid Plexus Carcinoma (CPC), a subtype of choroid plexus tumors (CPT), is a rare central nervous system neoplasm mostly affecting the pediatric population. The epidemiology of CPC is poorly understood due to the rarity of the disease. By analyzing the National Cancer Database (NCDB), we describe the demographic and social factors that influence the risk and current treatment of the cancer. Methods: We conducted a retrospective cohort analysis utilizing the 2018 National Cancer Database (NCDB) and included patients with Choroid Plexus Carcinoma with a histology-confirmed WHO grade III tumor, between ages 0-99 years (N = 202). Analysis was completed for the frequency of cases, types of treatment received, and overall survival within the pediatric population (age &lt; 18 years, N = 139) and the adult population. Demographic factors were analyzed using Pearson Chi-squared tests, and survival was estimated using Kaplan-Meier curves. Results: The majority of the cases analyzed were white (55.4%), male (54%), and pediatric patients (66.8%, mean age at diagnosis = 15.17 years) with an average Charlson-Deyo Score of 0.24. The mean age at diagnosis of the pediatric population was 2.34 years (min = less than 1 years old/diagnosed in utero, max = 16, std. deviation = 3.84) while the mean age at diagnosis of the adult population was 43.49 years (min = 18, max = 84, std. deviation = 18.23.) The most common primary site for CPC was malignant neoplasm of the cerebral ventricle (87.6%) followed by malignant neoplasm of the brain stem (5.9%). Surgical procedure of the primary site was performed in 92.6% of cases including local excision, subtotal resection, resection, radical resection, partial resection of a lobe of brain, lobectomy, and surgery NOS. Radiation was not used 71.3% of the time, but was more than three times as likely to be used in the adult population after surgery than in the pediatric population after surgery (44.4% vs 14.4%, p value &lt; 0.001). Most patients received chemotherapy (53%) with the administration of chemotherapy higher in the cohort less than 18 years old (69.8% versus 15.9%, p value &lt; 0.001). Multiagent chemotherapy was administered as the first course of therapy as the top chemotherapeutic choice (86%) especially among the pediatric population (88.6%) compared to the adult population (60%) Palliative care was not provided in any of the cases. There was no statistical significance difference between the general survival of CPC between the pediatric and adult population. Conclusions: Historically, CPC is known as a pediatric cancer, but this NCDB study suggests that the frequency of the adult population affected is not negligible (31.2%). There is a difference regarding the current treatment of CPC in the pediatric versus adult population. Further study is needed to determine the impact of treatment and the importance of socioeconomic factors on the survival of CPC.

Opiod Induced Pruritus: The Need for Palliative Care for a Palliative Medicine (S707)

e16251 Background: Multiple studies have shown a rise in the incidence of carcinoma among the pediatric and younger adult populations, including breast, kidney, and pancreas carcinomas. In contrast, there is little data on changes in the incidence of liver cancer in the pediatric and young adult population for primary liver carcinomas, especially for rare liver cancer such as fibrolamellar carcinoma and cholangiocarcinoma. This study determines the incidence and mortality of primary liver carcinomas in the pediatric and young adult population. Methods: Patients diagnosed with cholangiocarcinoma, fibrolamellar carcinoma, and hepatocellular carcinoma were selected from the National Cancer Database (NCDB) using histology codes 8160, 8171, and 8170. United States census data stratified by age groups from 2000 – 2022 was also collected. Years 2001 – 2009, for which there was no yearly census data, was estimated. Yearly incidence rates per age group were calculated, with ages of 0-9 years classified as the pediatric population and 11-35 years as the younger adult population. Linear regression models were made. Data was analyzed using R version 4.4.2 with α = 0.05. Results: There was a significant increase in the incidence of hepatocellular carcinoma among the younger adults from 2002 – 2022 (β = 0.0014, p = 0.00315), with a significant decrease in survival (β = -4.478, p = 0.00216), but no significant change in the incidence or survival in the pediatric population. Conversely, there was no significant increase in the incidence of fibrolamellar carcinoma among the younger adults, but there was a slight significant increase in incidence for the pediatric population (β = 0.0002, p = 0.04175) as well as a significant decrease in survival outcomes (β = -1.2990, p = 0.02548). While there was no incidence change in fibrolamellar carcinoma in the younger adult population, there was a significant decline in mortality (β = -2.342, p &lt; 0.0001). Finally, there was no significant change in incidence for cholangiocarcinoma among either the pediatric or young adult population. Conclusions: Together, these data show hepatocellular carcinoma and fibrolamellar carcinoma are increasing in the younger population, pointing towards the need for further study.

Improving Drug Therapy for Pediatric Patients: Unfinished History of Pediatric Drug Development.

In recent years, antipsychotic medications have increasingly been used in pediatric and geriatric populations, despite the fact that many of these drugs were approved based on clinical trials in adult patients only. Preliminary studies have shown that the “off-label” use of these drugs in pediatric and geriatric populations may result in adverse events not found in adults. In this study, we utilized the large-scale U.S. Food and Drug Administration (FDA) Adverse Events Reporting System (AERS) database to look at differences in adverse events from antipsychotics among adult, pediatric, and geriatric populations. We performed a systematic analysis of the FDA AERS database using MySQL by standardizing the database using structured terminologies and ontologies. We compared adverse event profiles of atypical versus typical antipsychotic medications among adult (18-65), pediatric (age < 18), and geriatric (> 65) populations. We found statistically significant differences between the number of adverse events in the pediatric versus adult populations with aripiprazole, clozapine, fluphenazine, haloperidol, olanzapine, quetiapine, risperidone, and thiothixene, and between the geriatric versus adult populations with aripiprazole, chlorpromazine, clozapine, fluphenazine, haloperidol, paliperidone, promazine, risperidone, thiothixene, and ziprasidone (p < 0.05, with adjustment for multiple comparisons). Furthermore, the particular types of adverse events reported also varied significantly between each population for aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (Chi-square, p < 10-6). Diabetes was the most commonly reported side effect in the adult population, compared to behavioral problems in the pediatric population and neurologic symptoms in the geriatric population. We also found discrepancies between the frequencies of reports in AERS and in the literature. Our analysis of the FDA AERS database shows that there are significant differences in both the numbers and types of adverse events among these age groups and between atypical and typical antipsychotics. It is important for clinicians to be mindful of these differences when prescribing antipsychotics, especially when prescribing medications off-label.

Expert consensus guidelines: Anomalous aortic origin of a coronary artery

Comparison of outcomes after MPFL reconstruction in adult vs pediatric populations: A systematic review of the literature.

The majority of reports on transfusion reactions address adult patients. Less is known about the types, incidence, and other clinical details of transfusion reactions in pediatric populations. Furthermore, to our knowledge, there have been no previous reports directly comparing these aspects between adults and pediatric patient populations to assess if there are differences. Between the period of January 1, 2011, and February 1, 2013, all reported adult and pediatric transfusion reactions at Vanderbilt University Medical Center (VUMC) were evaluated by transfusion medicine clinical service. The information was subsequently shared with the hemovigilance database. Data provided to hemovigilance included age, sex, blood product associated with the reaction, severity of the reaction, and the type of transfusion reactions. These were collated with hospital and blood bank information system-acquired data on overall admission and product transfusion. A total of 133,671 transfusions were performed at VUMC during the study period including 20,179 platelet (PLT) transfusions, 31,605 plasma transfusions, 79,933 red blood cell (RBC) transfusions, and 2154 cryoprecipitate transfusions. Over the same period, 108 pediatric and 277 adult transfusion reactions were recorded. This corresponds to an incidence of 6.2 reactions per 1000 transfusions within the pediatric (age < 21) population and an incidence of 2.4 reactions per 1000 transfusions within the adult population. In both adult and pediatric populations, transfusion reactions were most commonly associated with PLT, followed by RBC, and then plasma transfusions. Within the pediatric population, subset analysis identified multiple differences when compared to the adult population, including an increased incidence of allergic transfusion reactions (2.7/1000 vs. 1.1/1000, p < 0.001), febrile nonhemolytic transfusion reactions (1.9/1000 vs. 0.47/1000, p < 0.001), and hypotensive transfusion reactions (0.29/1000 vs. 0.078/1000, p < 0.05). Interestingly, while the reaction incidence was the same between sexes in adults, in pediatric patients, reactions were more common in male patients (7.9/1000 pediatric males vs. 4.3/1000 pediatric females, p < 0.01). To our knowledge this is the first study to provide detailed comparisons of acute transfusion reactions to all blood products between pediatric and adult populations at a single institution and supported by a single transfusion service and culture. Collectively these data provide insight into pediatric transfusion reactions and demonstrate a general increase in the incidence of transfusion reactions within the pediatric compared to adult population.

New daily persistent headache (NDPH) is a primary headache disorder characterized by the sudden onset of continuous pain and its intractability to treatment. It is more prevalent in the pediatric population than the adult population, but remains understudied and underdiagnosed. The purpose of the current article is to provide a current overview of new daily persistent headache in the pediatric and adolescent population, including history, pathophysiology, clinical findings, current and emerging treatment options, and the results of recent studies and meta-analyses. Despite recent studies and meta-analyses showing significant phenotypic overlap between chronic migraine and NDPH in the pediatric population, multiple recent studies have come to conflicting conclusions about the overlap of medication overuse in headache and pediatric NDPH. Recent studies reveal alterations in neuroimaging, particularly in functional connectivity, in patients with NDPH. Patients frequently remain treatment-refractory even to medications that have historically proven helpful in this population; however, new treatment options, including calcitonin gene-related peptide (CGRP) monoclonal antibodies, may be more effective. NPDH remains a perplexing and difficult-to-manage condition for both children and adults. Despite a higher prevalence in the pediatric population, there are relatively few studies to guide the evaluation and treatment of NDPH in pediatric and adolescent patients. Early treatment, both pharmacological and non-pharmacological, should be employed to reduce disability. Overall, further studies are needed to better understand pathogenesis and to identify more effective therapeutic strategies, both pharmacological and non-pharmacological.

The purpose of this study was to evaluate the current available literature on hip arthroscopy and determine the clinical indications in the pediatric patient population (age ≤ 18). In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), a comprehensive literature search was performed on the 23 October 2018 using PubMed, Cochrane Library, Embase and e-books to identify research surrounding the use of hip arthroscopy in the pediatrics. Exclusion criteria were studies that described joints other than the hip, animal studies, systematic reviews, open procedures and those that reported solely on patients aged 19-year-old and older. From 232 studies, 57 were reviewed in detail; 17 articles were removed as their indication fell into a category of ‘diagnostic hip arthroscopy for pain’ or no clear separation between the data on the adult and pediatric population could be made in a full text review of the paper. Eleven categories were identified as indications for hip arthroscopy in the pediatric population. At best a Grade C recommendation can be made to support the use of hip arthroscopy in the pediatric population. Our results support our hypothesis. Despite the exponential increase in hip arthroscopy over the last decade, limited evidence exists in support of its use in the pediatric (≤18) population. Our findings support the need for further research in delineating the indications for its use, as clearly arthroscopy may be advantageous in many situations, particularly in light of the alternatives.

This study aimed to develop a population pharmacokinetic (PK) model of ambrisentan in pediatric patients (8 to <18 years) with pulmonary arterial hypertension (PAH) and compare pediatric ambrisentan systemic exposure with previously reported adult data. Association of ambrisentan exposure with efficacy (6-minute walking distance) and safety (adverse events) were exploratory analyses. A population PK model was developed using pediatric PK data. Steady-state systemic exposure metrics were estimated for the pediatric population and compared with previously reported data in adult patients with PAH and healthy subjects. No covariates had a significant effect on PK parameters; therefore, the final covariate model was the same as the base model. The pediatric population PK model was a 2-compartment model including the effect of body weight (allometric scaling),first-order absorption and elimination, and absorption lag time. Steady-state ambrisentan exposure was similar between the pediatric and adult population when accounting for body weight differences. Geometric mean area under the concentration-time curve at steady state in pediatric patients receiving ambrisentan low dose was 3% lower than in the adult population (and similar in both populations receiving high dose). Geometric mean maximum plasma concentration at steady state in pediatric patients receiving low and high doses was 11% and 18% higher, respectively, than in the adult population. There was no apparent association in the pediatric or adult population between ambrisentan exposure and change in 6-minute walking distance or incidence of ambrisentan-related adverse events in pediatric patients. The similar ambrisentan exposure and exposure-response profiles observed in pediatric and adult populations with PAH suggests appropriateness of body-weight-based dosing in the pediatric population with PAH.

Background and Aims: Fecal microbiota transplantation (FMT) has been increasingly studied in the inflammatory bowel disease (IBD) population. However, most studies have focused on the adult population, and the safety and efficacy of FMT in a pediatric population is less well understood. This systematic review and meta-analysis investigates the safety and efficacy of FMT in a pediatric IBD population. Methods: A comprehensive literature search of publications published prior to 30 June 2022 was undertaken. Safety data, IBD-related outcomes, and microbiome analysis were obtained from these studies when accessible. Individual estimates of each study were pooled, and sensitivity analysis was conducted. Results: Eleven studies satisfied our eligibility criteria. The calculated pooled rate of adverse events was 29% (95% confidence interval [CI]: 15.0%, 44.0%; p &lt; 0.001; I2 = 89.0%, Q = 94.53), and the calculated pooled rate of serious adverse events was 10% (95% confidence interval [CI]: 6.0%, 14.0%; p = 0.28; I2 = 18.0%, Q = 9.79). One month after FMT, clinical response was achieved in 20/34 (58.8%) pediatric IBD patients, clinical remission was achieved in 22/34 (64.7%), and both clinical response and remission were achieved in 15/34 (44.1%) pediatric IBD patients. Conclusions: FMT can be a safe and effective treatment in the pediatric IBD population and may demonstrate improved safety and efficacy in the pediatric population compared to the adult population. However, our results are limited by a lack of established protocol as well as long-term follow-up for FMT in a pediatric IBD population.

Duloxetine, a selective serotonin (5-hydroxytryptamine) and norepinephrine reuptake inhibitor, has been approved since 2004 for the treatment of adults with major depressive disorder (MDD). It is currently not approved for use in pediatric patients (aged <18 years) with MDD. The clinical development program for duloxetine in the pediatric MDD population, which consisted of three clinical studies, provided extensive data on the safety, tolerability, and pharmacokinetics of duloxetine across a wide dose range in pediatric patients of differing ages, sex, body weights, and sexual maturation. The objectives were to characterize the pharmacokinetics of duloxetine based on population modeling following daily oral administration in children and adolescents aged 7-17 years diagnosed with MDD; to estimate the magnitude of between- and within-patient variability; to identify potential patient factors affecting duloxetine pharmacokinetics, and to compare duloxetine pharmacokinetics in the pediatric population with those characterized in adults. The analyses meta-dataset was created from pharmacokinetic and demographic data available from one phase II (open-label) and two phase III (randomized, double-blind) clinical trials of duloxetine in children and adolescents. Patients received 20-120 mg of oral duloxetine once daily. Duloxetine concentrations (a total of 1,581 concentrations) were obtained from 428 patients: 34% were children (aged 7-11 years) and 66% were adolescents (aged 12-18 years). Population modeling analyses were performed using nonlinear mixed-effects modeling and the first-order conditional estimation method with interaction. Patient factors were assessed for their potential influence on duloxetine apparent clearance (CL/F) and apparent volume of distribution (V d/F). Duloxetine pharmacokinetic parameters and model-predicted duloxetine concentrations at steady state in the pediatric population were compared with those in adults. Duloxetine pharmacokinetics in pediatric patients was described by a one-compartmental model. Typical values of CL/F, V d/F, and half-life (t 1/2) at 60 mg/day of duloxetine were 79.7 L/h, 1,200 L, and 10.4 h, respectively. The between-patient variability in CL/F and V d/F was 68 and 87%, respectively, while within-patient variability was 57% (proportional error) and 2.04 ng/mL (additive error). Body surface area (BSA), dose, and race had a statistically significant effect on duloxetine pharmacokinetics. With a 2.2-fold increase in BSA, the CL/F increased about twofold. A sixfold increase in dose (20 to 120 mg) decreased CL/F by 32%. In American Indian patients, V d/F was 131% higher than the other races combined. Age, sex, body mass index, serum creatinine, cytochrome P450 2D6 predicted phenotype, and menarche status did not have a statistically significant effect. Estimates of CL/F and V d/F were higher in the pediatric population than in adults; subsequently, the average steady-state duloxetine concentration was approximately 30% lower in the pediatric population than in adults. Duloxetine pharmacokinetics was similar in children and adolescents with MDD. The statistically significant effects of dose, BSA, and race on duloxetine pharmacokinetics in pediatric patients did not appear to be clinically meaningful. At a given dose, the typical steady-state duloxetine concentrations in the pediatric population were lower than in adults, and the distribution of steady-state duloxetine concentrations in pediatric patients were typically in the lower range of concentrations in adults.