Pediatric and emergency medicine resident comfort assessing and treating pediatric pain across pediatric age groups.

Aim: Assess pediatric and emergency medicine (EM) resident comfort treating and assessing pediatric pain. Materials & methods: Pediatric and EM residents at a single institution (SIUH Northwell Health in New York) completed an anonymous survey 6 months into the academic year regarding comfort assessing and treating pediatric pain. Results: A total of 40 (16/24 EM and 24/24 pediatric) residents completed this survey: 20% (8/24) pediatric first year residents, 40% (16/40) pediatric second year and above, 20% (8/40) EM first year and 20% (8/40) EM second year and above. A 46% (11/24) pediatric and 12% (2/16) EM residents were comfortable assessing neonatal pain (p < 0.05). A 38% (9/24) pediatric residents were comfortable treating neonatal pain compared with 12% (2/16) EM residents (p < 0.05). Both resident groups reported increasing comfort assessing and treating pain with increasing patient age. Conclusion: Both residents groups reported limitations in comfort assessing and treating pediatric pain, especially in younger patients. Education for both groups is important to optimize pediatric pain management.

Pediatric pain is common, and often underassessed and undertreated. Pediatric and emergency medicine (EM) residents care for pediatric patients with pain and must be able to appropriately assess and treat this pain. For this study, pediatric and EM residents at a single institution (SIUH Northwell Health in New York) completed an anonymous survey 6 months into the academic year regarding comfort assessing and treating pain and comfort prescribing pain medications across pediatric age ranges. In this study, 40 (16/24 EM and 24/24 pediatric) residents completed this anonymous survey. Of the 40 residents, 20% (8/24) were pediatric first year residents, 40% (16/40) were second or third year pediatric residents, 20% (8/40) were EM first year residents and 20% (8/40) were second, third or fourth year residents. About 46% (11/24) of pediatric residents and 12% (2/16) of EM residents were comfortable assessing neonatal pain. With increasing patient age, pediatric residents and EM residents comfort in assessing pediatric pain trended up (93.3% EM residents comfortable assessing pain in teenage patients). About 38% (9/24) of pediatric residents were comfortable treating neonatal pain as compared with 12% (2/16) of EM residents. While pediatric residents were significantly more comfortable treating pain in age categories from neonate to adolescents as compared with EM residents, both pediatric and EM residents reported increasing comfort in treating pediatric pain with increasing patient age. Limitations in comfort assessing and treating pediatric pain exist for both specialties. Education for both groups is important to optimize pediatric pain management.

Emergency department visits and hospitalizations for pediatric vaso-occlusive pain events during the COVID-19 pandemic.

The coronavirus SARS-CoV-2 (COVID-19) pandemic altered all aspects of life, including healthcare. During the pandemic, social distancing led to decreased transmission of typical viral illnesses, leading to a decrease in these pediatric admissions. Studies have shown that pediatric emergency department (ED) visits and hospitalizations decreased during the pandemic, which may have led to some unmet healthcare needs and delays in treatment. Little is known about the effect of the COVID-19 pandemic on ED visits and hospitalizations specifically for pediatric sickle cell pain. A retrospective review across hospitals in the Northwell Health system was conducted to compare the ED visits and hospitalizations for pediatric patients with sickle cell pain during 2020 (the year of the pandemic), the following year (2021), and the 2 years prior to the pandemic (2018, 2019). The average length of stay for patients hospitalized with vaso-occlusive events was also compared between these years. Total 511 patient encounters for patients seen and discharged home from the ED and 985 hospitalization encounters were included over the 4-year timespan. ED visits per year decreased significantly in 2020 compared with the 2 years prior (p < .001): 91 visits in 2020, 162 visits in 2019, and 143 visits in 2018. The number of ED visits for pediatric vaso-occlusive events trended upward in 2021 to 115. Hospitalizations also decreased in 2020 compared to the 2 years prior (n = 202 vs 196; p < .001), compared with 298 in 2019 and 289 in 2018. The number of patients hospitalized remained stable in 2021 (n = 202 vs 196). There was a statistically significant increase in the median length of stay in 2020 compared to years prior (p = .002): median (interquartile range [IQR]): 4.0 days (2-6 days) in 2020 compared to 3.0 days (2-5 days) in 2018 and 2019. ED encounters and hospitalizations for pediatric patients with sickle cell disease pain decreased during the pandemic; however, admitted patients had a longer median length of stay.

Ketamine as an Adjunct for Treatment of Methotrexate-induced Neurotoxicity.

Methotrexate (MTX) is used in the treatment of several childhood cancers and is a main component of the treatment regimen for osteosarcoma. MTX has been linked with side effects of varying severity; headaches, nausea, emesis, lethargy, blurred vision, aphasia, hemiparesis, paresis, convulsions, leukoencephalopathy, and arachnoiditis are symptoms of MTX toxicity. MTX-induced neurotoxicity can occur in up to 15% of patients receiving high-dose MTX. The effects may be transient but can have life-threatening implications, sometimes requiring intubation for respiratory support and airway protection. Elevated homocysteine levels in the cerebrospinal fluid are documented in cases of MTX-induced neurotoxicity; dextromethorphan is used as an initial treatment for MTX-induced neurotoxicity as it works as a noncompetitive antagonist for the N-methyl D-aspartate receptors and suppresses homocysteine activity. In severe cases requiring intubation, medications for sedation are utilized. Ketamine is also an N-methyl D-aspartate receptor antagonist, and as such, may be considered as an optimal treatment choice when sedation is required. We describe the use of ketamine in a pediatric patient with MTX-induced neurotoxicity. The use of ketamine in the treatment of MTX-induced neurotoxicity has not been described in the literature.

The Use of Sunitinib as Maintenance Therapy in a Pediatric Patient With a Poorly Differentiated Thymic Carcinoma.

BACKGROUND: Thymic carcinomas are rare aggressive mediastinal tumors with a median survival of 2 years. OBSERVATION: We present a pediatric patient who was diagnosed with metastatic thymic carcinoma and showed continuous improvement of his primary mass and lung metastases with a regimen of cisplatin/docetaxel followed by long-term maintenance therapy with sunitinib for over 5 years. CONCLUSIONS: This report demonstrates a long-term positive treatment effect using chemotherapy followed by sunitinib in an advanced thymic carcinoma. We are not aware of other reports of pediatric patients with metastatic thymic carcinoma treated with sunitinib maintenance who maintained a durable response for this prolonged period of time.

Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain.

ABSTRACT: We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference effect size for each comparison and performed a random-effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86%). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low; therefore, the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models, and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.

Implementation of a Multi-Modal Palliative Care Curriculum for Pediatric Residents.

OBJECTIVES: To evaluate the feasibility and efficacy of a new multi-modal pediatric palliative care curriculum. We sought to determine the effect on comfort in palliative care, knowledge, and change in behavior by utilizing these skills with patients, and determine which modalities were most effective for residents. STUDY DESIGN: 25 pediatric residents were exposed to the 4-part curriculum. The modalities utilized in this curriculum included didactics, role-play, videos, case-discussion, small group activities, simulation, poetry and reflection. RESULTS: The pediatric residents self-reported an increase in comfort and knowledge of the components of pediatric palliative care after this curriculum. In addition, 74% of residents were able to identify a patient experience in which a component of the palliative care curriculum was utilized directly in patient care. The effectiveness of techniques utilized in this multimodal curriculum varied; residents reported that the poetry and reflection components were less effective, as compared with the role-play, simulation and other active learning components. CONCLUSIONS: Implementation of a multi-modal palliative care curriculum was effective in increasing knowledge in palliative care, comfort in breaking bad news, and caring for patients with palliative care needs. This can be translated into a change in behavior to utilize these new skills in the care of various patients in pediatrics. Among the various techniques used to teach this curriculum, residents reported that the techniques that most incorporated active learning and were directly applicable to the professional role of the resident were rated most valuable. This curriculum was well received, feasible and effective for pediatric residents.

The effects of sample handling on proteomics assessed by reverse phase protein arrays (RPPA): Functional proteomic profiling in leukemia.

Reverse phase protein arrays (RPPA) can assess protein expression and activation states in large numbers of samples (n > 1000) and evidence suggests feasibility in the setting of multi-institution clinical trials. Despite evidence in solid tumors, little is known about protein stability in leukemia. Proteins collected from leukemia cells in blood and bone marrow biopsies must be sufficiently stable for analysis. Using 58 leukemia samples, we initially assessed protein/phospho-protein integrity for the following preanalytical variables: 1) shipping vs local processing, 2) temperature (4 °C vs ambient temperature), 3) collection tube type (heparin vs Cell Save (CS) preservation tubes), 4) treatment effect (pre- vs post-chemotherapy) and 5) transit time. Next, we assessed 1515 samples from the Children's Oncology Group Phase 3 AML clinical trial (AAML1031, NCT01371981) for the effects of transit time and tube type. Protein expression from shipped blood samples was stable if processed in ≤72 h. While protein expression in pre-chemotherapy samples was stable in both heparin and CS tubes, post-chemotherapy samples were stable in only CS tubes. RPPA protein extremes is a successful quality control measure to identify and exclude poor quality samples. These data demonstrate that a majority of shipped proteins can be accurately assessed using RPPA. SIGNIFICANCE: RPPA can assess protein abundance and activation states in large numbers of samples using small amounts of material, making this method ideal for use in multi-institution clinical trials. However, there is little known about the effect of preanalytical handling variables on protein stability and the integrity of protein concentrations after sample collection and shipping. In this study, we used RPPA to assess preanalytical variables that could potentially affect protein concentrations. We found that the preanalytical variables of shipping, transit time, and temperature had minimal effects on RPPA protein concentration distributions in peripheral blood and bone marrow, demonstrating that these preanalytical variables could be successfully managed in a multi-site clinical trial setting.

Pediatric Research and Scholarship Committee: Single Institution Initiative to Enhance Scholarly Activity of Pediatric Residents.

OBJECTIVE: We sought to improve scholarly activity of pediatric residents by providing residents with support and guidance from a committee of faculty and staff members dedicated to advancing research within the program while requiring minimal additional funding or resources. APPROACH: Established in 2012, the Pediatric Research and Scholarship Committee (PRSC) ascertained research interests of pediatric residents and matched residents with scholarly activity mentors based on mutual interests and goals. We measured change in scholarly activity of residents after the development of the PRSC by reviewing resident presentations at national/regional meetings and manuscripts published pre- and post-PRSC. OUTCOMES: The average number of conference presentations at regional/national meetings per resident ratio increased from 0.13 over the 2 years prior to the PRSC to an average of 0.34 over the 2 years post-PRSC, with the overall increase sustained over the seven years post-PRSC (0.13 pre-PRSC vs 0.48 post-PRSC, P < .01). In addition, published peer-reviewed manuscripts with resident primary authorship increased after the initiation of the PRSC from 0 publications over the 2 years pre-PRSC to a total of 25 publications over the 7 years post-PRSC (P = .01). An average of 27% of graduating residents with limited PRSC exposure (2 graduating classes) had presented at a regional/national conference during residency, as compared to 50% of graduating residents over the first 2 years of full PRSC exposure, and 59% of all graduating residents with full exposure to the PRSC over the last 5 years (P = .03). DISCUSSION: Implementation of a research committee comprised of dedicated faculty can play a vital role in stimulating and sustaining productivity in resident research and scholarly activity. Our model can be adopted by other residency programs seeking to advance resident scholarly activities.

The evaluation of lymphopenia in infants exposed to opioids in-utero.

BACKGROUND: Chronic use of opioids is associated with hematologic and immunologic effects, including lymphopenia. Despite an increase in opioid use during pregnancy, little is known about the potential immunologic effects on the neonate after exposure to opioids in-utero. We aimed to evaluate the presence of lymphopenia among neonates exposed to opioids in-utero. METHODS: We conducted a retrospective chart review of infants admitted to the neonatal intensive care unit (NICU) of a single institution after exposure to opioids in-utero. We compared the lymphocyte counts of this population to a control NICU population. RESULTS: A higher percentage of neonates exposed to opioids in-utero were lymphopenic compared to our control population (44% vs 24%, p = 0.035). CONCLUSIONS: This is the first study we are aware of, that investigated an association between neonatal lymphopenia and opioid exposure in-utero. Further studies to explore clinical implications of this finding are needed.

Pain Management for Sickle Cell Disease in the Pediatric Emergency Department: Medications and Hospitalization Trends.

The majority of emergency department (ED) visits and hospitalizations for patients with sickle cell disease (SCD) are pain related. Adequate and timely pain management may improve quality of life and prevent worsening morbidities. We conducted a retrospective chart review of pediatric patients with SCD seen in the ED, selected by sickle cell-related ICD-9 codes. A total of 176 encounters were reviewed from 47 patients to record ED pain management and hospitalization trends. Mean time to pain medication administration was 63 minutes. Patients received combination (nonsteroidal anti-inflammatory drug [NSAID] + narcotic) pain medications for initial treatment at a minority of ED encounters (19%). A higher percentage of patients who received narcotics alone as initial treatment were hospitalized as compared with those who received combination treatment initially ( P= 0.0085). Improved patient education regarding home pain management as well as standardized ED guidelines for assessment and treatment of sickle cell pain may result in superior and more consistent patient care.

A unique case of Shwachman-Diamond syndrome presenting with congenital hypopituitarism.

Shwachman-Diamond syndrome (SDS) is an autosomal recessive bone marrow failure syndrome typically characterized by neutropenia and pancreatic dysfunction, although phenotypic presentations vary, and the endocrine phenotype is not well-described. We report a unique case of a patient with SDS who initially presented with hypoglycemia and micropenis in the newborn period and was diagnosed with congenital hypopituitarism. We are not aware of any other cases of SDS documented with this combination of complex endocrinopathies.

Wnt inhibition leads to improved chemosensitivity in paediatric acute lymphoblastic leukaemia.

While childhood acute lymphoblastic leukaemia (ALL) is now highly curable, the dismal prognosis for children who relapse warrants novel therapeutic approaches. Previously, using an integrated genomic analysis of matched diagnosis-relapse paired samples, we identified overactivation of the Wnt pathway as a possible mechanism of recurrence. To validate these findings and document whether Wnt inhibition may sensitize cells to chemotherapy, we analysed the expression of activated ß-catenin (and its downstream target BIRC5) using multiparameter phosphoflow cytometry and tested the efficacy of a recently developed Wnt inhibitor, iCRT14, in ALL cell lines and patient samples. We observed increased activation of ß-catenin at relapse in 6/10 patients. Furthermore, treatment of leukaemic cell lines with iCRT14 led to significant downregulation of Wnt target genes and combination with traditional chemotherapeutic drugs resulted in a synergistic decrease in viability as well as a significant increase in apoptotic cell death. Finally, pre-treatment of purified blasts from patients with relapsed leukaemia with the Wnt inhibitor followed by exposure to prednisolone, restored chemosensitivity in these cells. Our results demonstrate that overactivation of the Wnt pathway may contribute to chemoresistance in relapsed childhood ALL and that Wnt-inhibition may be a promising therapeutic approach.

A phase I study of EZN-3042, a novel survivin messenger ribonucleic acid (mRNA) antagonist, administered in combination with chemotherapy in children with relapsed acute lymphoblastic leukemia (ALL): a report from the therapeutic advances in childhood leukemia and lymphoma (TACL) consortium.

To address the therapeutic challenges in childhood relapsed ALL, a phase 1 study combining a survivin mRNA antagonist, EZN-3042, with reinduction chemotherapy was developed for pediatric patients with second or greater bone marrow relapses of B-lymphoblastic leukemia. EZN-3042 was administered as a single agent on days -5 and -2 and then in combination with a 4-drug reinduction platform on days 8, 15, 22, and 29. Toxicity and the biological activity of EZN-3042 were assessed. Six patients were enrolled at dose level 1 (EZN-3042 2.5 mg/kg/dose). Two dose-limiting toxicities were observed: 1 patient developed a grade 3 γ-glutamyl transferase elevation and another patient developed a grade 3 gastrointestinal bleeding. Downmodulation of survivin mRNA and protein were assessed after single-agent dosing and decreased expression was observed in 2 of 5 patients with sufficient material for analysis. Although some biological activity was observed, the combination of EZN-3042 with intensive reinduction chemotherapy was not tolerated at a dose that led to consistent downregulation of survivin expression. The trial was terminated following the completion of dose level 1, after further clinical development of this agent was halted.

A primary cardiac sarcoma with features of a desmoplastic small round cell tumor in an adolescent male.

Malignant primary cardiac tumors are very rare.Desmoplastic small round cell tumors are also rare tumors and,when present, are generally found in the abdomen. We report a case of an adolescent male who presented with chest pain,abdominal pain, and difficulty in breathing, who was found to have a primary cardiac sarcoma with several characteristic features of a desmoplastic small round cell tumor.

Neoplasia in familial dysautonomia: a 20-year review in a young patient population.

We reviewed the charts of all patients with familial dysautonomia (n = 631) and found that 2% had been diagnosed with tumors. We hypothesize that the IkappaB Kinase-associated protein gene mutation, which causes aberrant RNA splicing in patients with familial dysautonomia, may contribute to tumorigenesis in this genetically homogenous patient population.