Phase I Trial of GD2.CART Cells Augmented With Constitutive Interleukin-7 Receptor for Treatment of High-Grade Pediatric CNS Tumors.

PURPOSE: T cells modified with chimeric antigen receptors (CARTs) have demonstrated efficacy for hematologic malignancies; however, benefit for patients with CNS tumors has been limited. To enhance T cell activity against GD2+ CNS malignancies, we modified GD2-directed CART cells (GD2.CARTs) with a constitutively active interleukin (IL)-7 receptor (C7R-GD2.CARTs). METHODS: Patients age 1-21 years with H3K27-altered diffuse midline glioma (DMG) or other recurrent GD2-expressing CNS tumors were eligible for this phase I trial (ClinicalTrials.gov identifier: NCT04099797). All subjects received standard-of-care adjuvant radiation therapy or chemotherapy before study enrollment. The first treatment cohort received GD2.CARTs alone (1 × 107 cells/m2), and subsequent cohorts received C7R-GD2.CARTs at two dose levels (1 × 107 cells/m2; 3 × 107 cells/m2). Standard lymphodepletion with cyclophosphamide and fludarabine was included at all dose levels. RESULTS: Eleven patients (age 4-18 years) received therapy without dose-limiting toxicity. The GD2.CART cohort did not experience toxicity, but had disease progression after brief improvement of residual neurologic deficits (≤3 weeks). The C7R-GD2.CART cohort developed grade 1 tumor inflammation-associated neurotoxicity in seven of eight (88%) cases, controllable with anakinra. Cytokine release syndrome was observed in six of eight (75%, grade 1 in all but one patient) and associated with increased circulating IL-6 and IP-10 (P < .05). Patients receiving C7R-GD2.CARTs experienced temporary improvement from baseline neurologic deficits (range, 2 to >12 months), and seven of eight (88%) remained eligible for additional treatment cycles (range 2-4 cycles). Partial responses by iRANO criteria were observed in two of seven (29%) patients with DMG treated by C7R-GD2.CARTs. CONCLUSION: Intravenous GD2.CARTs with and without C7R were well tolerated. Patients treated with C7R-GD2.CARTs exhibited transient improvement of neurologic deficits and increased circulating cytokines/chemokines. Treatment with C7R-GD2.CARTs represents a novel approach warranting further investigation for children with these incurable CNS cancers.

Antipsychotics in child and adolescent patients with major depressive disorder: A retrospective analysis of prescribing patterns.

Introduction: Depression rates in children/adolescents in the United States have increased in the last 10 years. Fluoxetine and escitalopram are the only 2 antidepressants approved for the treatment of major depression disorder (MDD) in children/adolescents. In adults, some antipsychotics are approved for augmented treatment of MDD. However, there is limited research on antipsychotic augmentation in child/adolescent MDD. Methods: This retrospective chart review evaluated antipsychotic prescribing for MDD in hospitalized patients aged 4 to 17 years to determine the frequency of prescribing antipsychotics for MDD and what factors influence the addition of an antipsychotic. For inclusion, patients were diagnosed with MDD and not on an antidepressant or antipsychotic before admission. Binomial logistic regression was used to analyze variables with prescribed antipsychotics as the dependent variable. Results: There were 6.8% of patients prescribed an antipsychotic. Binomial logistic regression analysis found that increased age (odds ratio [OR] 1.28; 95% CI = 1.045, 1.568; P = .017) and multiple admissions within 1 year (OR 3.277; 95% CI = 2.283, 4.705; P < .001) were associated with the use of antipsychotics in patients with MDD. Posttraumatic stress disorder and disruptive mood dysregulation disorder were also associated with the use of antipsychotics. Discussion: Careful consideration should be taken when using off-label antipsychotics in children due to limited studies on efficacy. Future research is warranted to assess the efficacy and safety of these agents in children and adolescents.

Consumer perception, knowledge, and uses of cannabidiol.

Introduction: The legalization of cannabidiol (CBD) across the United States, in varying degrees, has made CBD easily accessible to consumers for complementary and medical purposes. However, there is a paucity of scientific evidence on the benefits and risks of commercially available CBD. In the literature, 2 studies have gathered consumer perceptions and attitudes on cannabis products, specifically CBD, using survey-based questionnaires. This study aimed to build on the aforementioned studies in obtaining consumer perception and knowledge of CBD products using a national survey-based questionnaire. Methods: Respondents were recruited through an anonymous, nationwide, online survey administered through Qualtrics in the United States from March 28 to April 30, 2021. The survey consisted of demographics, perceived efficacy and safety of CBD, and resources to obtain CBD information. The survey responses were reported using descriptive statistics along with median and interquartile range for the Likert portion. Results: A total of 1158 respondents accessed the survey. The median age was 43 and 50% of respondents were female. The uses for CBD included neurological disorders, pulmonary conditions, gastrointestinal disorders, and chronic pain. The most commonly reported safety concern related to taking CBD was anxiety. Participants agreed that CBD is safe when used responsibly for medical use, and social media was the main source used to obtain information about CBD. Discussion: Respondents who used CBD for a condition thought it was helpful; however, most of the adverse effects were rated as moderate to severe, requiring medical attention from a health care professional, hospital, or emergency room visit.

Comparison of inpatient psychiatric medication management in gender diverse youth with cisgender peers.

Introduction: The primary objective was to determine if gender diverse (GD) youth receive different psychotropic prescribing compared with cisgender (CG) peers with the same diagnosis. Secondary objectives include evaluation of readmission rates and the effect of gender-affirming hormone therapy (GAHT) on psychiatric outcomes in transgender (TG) patients. Methods: A total of 255 GD youth patients were retrospectively matched to CG controls based on age, primary discharge diagnosis, and year of admission. Data collection included psychotropic medications at admission and discharge, baseline demographics, time to readmission, and total number of readmissions within 6 months. Use of GAHT was also documented. Wilcoxon signed rank test was used for continuous and χ2 for nominal data with an a priori α of 0.05. Results: MDD was the primary discharge diagnosis in 74% of patients. GD youth were more likely to present on antidepressants (P = .031) and antipsychotics (P = .007), and to be discharged with antipsychotics (P = .003). They were additionally more likely to be readmitted within 30 days of discharge (P = .032). TG youth on GAHT (13%) had fewer readmissions (P = .046) than those not on GAHT, but there were no differences in psychotropic prescribing. Discussion: Higher antipsychotic and antidepressant prescribing were seen in the GD population despite the same mental health diagnosis. Despite higher prescribing in the GD population, patients presented for readmission within 30 days more frequently, which may represent a need for more rigorous transitions-of-care practices in this population.

Fulminant Anti-Myelin Oligodendrocyte Glycoprotein-Associated Cerebral Cortical Encephalitis: Case Series of a Severe Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Phenotype.

BACKGROUND: We describe a cohort of children with severe myelin oligodendrocyte glycoprotein (MOG)-IgG-associated cerebral cortical encephalitis (CCE), manifesting with bilateral cortical cytotoxic edema and critical neurological illness. METHODS: We retrospectively reviewed our pediatric MOG antibody-associated disease (MOGAD) database and identified patients with specific radiographic pattern of bilateral, multifocal cortical cytotoxic lesions. We collected demographic, clinical, and outcomes data from these patients and compared select variables with radiographically distinct cerebral MOGAD syndromes (case-control analysis). We assessed the correlation of quantitative clinical variables with severity/outcomes measures using simple linear regression. RESULTS: Sixty-five of 88 total MOGAD cases had cerebral disease, and six of 88 met inclusion criteria for fulminant CCE (f-CCE). Age range was 2 to 7 years; five of six were male. Six of six were critically ill with severe encephalopathy and seizures, two of six required barbiturate coma, and two of six required invasive intracranial pressure monitoring. Six of six required treatment escalation beyond steroids. Four of six had favorable outcome; two of six had moderate-severe disability. Compared with other cerebral MOGAD cases (n = 59), children with f-CCE were more likely to have critical illness and poor neurological outcomes scores. Neurofilament light chain and treatment latency positively correlated with intensive care unit length of stay and outcomes scores; cerebrospinal fluid (CSF) white blood cell count and neutrophil-to-lymphocyte ratio did not. CONCLUSIONS: Pediatric CCE with bilateral cytotoxicity is associated with more fulminant disease and worse outcomes than other cerebral MOGAD syndromes.

Pediatric Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a demyelinating disease with a high relapse rate and risk of disability accrual. The condition is an astrocytopathy, with antibodies to the aquaporin-4 (AQP4) water channel being detected in AQP4-IgG seropositive disease. Presentation is uncommon in the pediatric age range, accounting for about 3%-5% of cases. NMOSD is more prevalent in populations of Black or East Asian ancestry. Core clinical syndromes include optic neuritis, acute myelitis, area postrema syndrome, acute brainstem syndrome, acute diencephalic syndrome, and symptomatic cerebral syndrome. First-line treatment options in pediatrics include rituximab, azathioprine, and mycophenolate mofetil. Over half of children with AQP4-IgG seropositive NMOSD develop permanent disability, particularly in visual and motor domains. Novel therapeutic targets in the adult population have been developed and are changing the treatment landscape for this disorder.

Initiation of Antipsychotic Treatment for Amphetamine Induced Psychosis and Its Impact on Length of Stay.

Introduction: A risk of amphetamine use is amphetamine-induced psychosis (AIP). Symptoms of AIP include hallucinations, delusions, and agitation. While AIP may resolve with abstinence from amphetamines, antipsychotics are commonly used despite not being FDA approved. The primary objective of this study was to compare length of stay (LOS) for patients with AIP treated with antipsychotics vs untreated. Secondary aims were to determine antipsychotic prescribed, proportion of patients utilizing as needed doses, time to initiation, and readmissions. Methods: A retrospective chart review conducted at an academic medical center identified adult participants who were diagnosed with AIP, admitted to inpatient psychiatry service, and had a urine drug screen (UDS) positive for amphetamines. Patients were excluded if they were already taking an antipsychotic, had active prescriptions for amphetamine salts, or were in the emergency department for more than 48 hours. Demographics were assessed with descriptive statistics. Length of stay was compared between treatment groups using Kruskal-Wallis. Secondary aims were assessed using chi-square, Mann-Whitney U, and Kruskal-Wallis. Results: Sixty-nine patients were included. Median LOS for patients treated with antipsychotics (n = 35) was longer than untreated patients (n = 34), (5 days vs 2.5 days, P = .001). Type of antipsychotic used and time to initiation of antipsychotic were not found to affect LOS. There was no difference in readmissions rates and positive UDS on readmission between groups. Conclusion: This study found patients with scheduled antipsychotics for AIP had a longer LOS than patients who did not receive scheduled antipsychotics. Future studies are needed to evaluate antipsychotic use in AIP.

Effects of Erythrocytapheresis Procedures on Delayed Bone Marrow Conversion in Sickle Cell Disease.

The imaging appearances of the skeletal system have been well documented in sickle cell disease (SCD) but there is limited information about the impact of SCD treatments on skeletal abnormalities. We present two patients with SCD maintained on long-term erythrocytapheresis and the changes to their skeletal abnormalities on neuroimaging with this treatment. We observed a reversal of the bone marrow conversion process and the skull appearance was age appropriate without any radiographic findings of iron overload in the patients.

Implementation and Outcomes of COVID-19 Vaccinations at a Child and Adolescent Psychiatric Hospital.

Increasing coronavirus disease 2019 (COVID-19) vaccination rates has been identified by the US Centers of Disease Control and Prevention as critical to ending the COVID-19 pandemic.1 On May 10, 2021, the Pfizer-BioNTech COVID-19 vaccine (BNT162b2; Pfizer, Inc, New York, New York, and BioNTech SE, Mainz, Germany) was approved for emergency use authorization by the US Food and Drug Administration for patients 12 years of age or older. Here we report a retrospective study describing the implementation of a COVID-19 vaccination program at our child and adolescent psychiatric hospital. To our knowledge, this is the first report detailing the administration of the COVID-19 vaccination in this setting.

Assessing pharmacy students' knowledge and perceptions of urine drug testing following a pharmacy skills laboratory.

INTRODUCTION: Urine drug tests (UDTs) are commonly used in the healthcare setting to monitor adherence, abuse, and diversion of controlled substances. The goal of our study was to assess the knowledge and perceptions of third-year pharmacy students on UDTs following an educational experience. METHODS: Third-year pharmacy students completed pre- and post-questionnaires following a skills laboratory focused on the use of UDTs in clinical settings. The 34-item questionnaires consisted of three domains: demographics, knowledge regarding UDTs, and personal perceptions of UDTs. A pre-lab teaching podcast was assigned prior to the laboratory session, and two clinical cases were discussed during the live UDT segment. Descriptive statistics were used to assess demographics, and changes in knowledge and perceptions of UDTs were evaluated using chi-square and Mann-Whitney U, respectively, with an a priori alpha of 0.05. RESULTS: One hundred twenty students were included in the analysis. Students in the laboratory were predominately female (n = 72, 60%), Caucasian (n = 84, 70%), and had no prior training with UDTs (n = 104, 86.7%). Student knowledge of UDT interpretation significantly increased from 57% to 71% (four and five correct answers out of seven, respectively). Confidence interpreting UDTs and answering questions related to UDTs also increased significantly. Students felt the laboratory experience was valuable, with 84.2% agreeing or strongly agreeing. CONCLUSIONS: Educational programming focused on UDTs improves student confidence interpreting results and knowledge related to the use of UDTs.

A nationwide survey of pharmacy students' knowledge and perceptions regarding medical cannabis.

OBJECTIVE: The primary objective of this study was to compare knowledge and perceptions of medical cannabis (MC) between pharmacy students who attended schools where MC was legal and illegal. DESIGN: A nationwide anonymous survey regarding MC was distributed to pharmacy students. The survey consisted of the following sections: (1) demographics and personal factors, (2) knowledge assessment of indications and adverse effects of MC, and (3) perceptions assessment. SETTING AND PARTICIPANTS: Equal numbers of pharmacy schools were selected and sent surveys based on geographical regions, private versus public universities, and the state's legal status of MC for first through fourth-year pharmacy students to complete. OUTCOME MEASURES: Student knowledge of MC indications and adverse effects were treated as quizzes. Median percentage correct and whether students passed the quizzes (≥ 70%) were evaluated based on the state's legal status. Students' perceptions were similarly compared. RESULTS: A total of 629 students accessed the survey. Most students who completed the survey attended pharmacy schools where MC was illegal (55%), were female (68%), and had personally tried cannabis (53%). Overall, 91% of students believed that MC should be legalized nationally. A low number of students correctly identify approved indications with 14.8% of students in states with MC legalization scoring greater than 70% compared with 15.9% of students in states without MC legalization (P = 0.748). Similar findings were seen in the side effects quiz with only 6.1% of students in states with legal MC scoring greater than 70% compared with 7.4% of students where MC is illegal (P = 0.569) There were minimal differences in students' perceptions of MC based on the states' legal status. CONCLUSION: Our study continues to highlight that pharmacy students lack knowledge and preparation to counsel and educate on MC. With increasing state legalizations, pharmacy schools need to address this knowledge gap to ensure optimal patient care.

Determination of combination therapy prescribing patterns for the treatment of acute agitation in psychiatric patients: A regression model of patient diagnoses and demographics.

INTRODUCTION: Guidelines for the treatment of acute agitation typically recommend monotherapy with an antipsychotic or a benzodiazepine, but combination therapy is frequently used in practice. We created a regression model to identify which factors lead to the prescribing of combination therapy for acute agitation on a psychiatry unit. METHODS: We collected retrospective data from hospitalized patients in the psychiatry unit. An a priori alpha of 0.05 was used for binary logistic regression models to determine if and how the number of prescribed medications for acute agitation was influenced by: age, sex, race, cardiovascular comorbidities, and psychiatric diagnoses. RESULTS: We identified 1998 encounters from 1200 patients. Patients are significantly more likely to be prescribed combination therapy if they are young, male, and of non-white race or have a diagnosis of central nervous system stimulant use, hallucinogen use, depression, bipolar, cluster B personality, or psychosis. Patients are significantly more likely to be prescribed monotherapy if they have cardiovascular comorbidity or have neurocognitive disorder. DISCUSSION: Several demographic or diagnostic factors predict combination therapy prescribing. Acute agitation guidelines should be reviewed to include more clear instructions on combination therapy use.

Medical Students' Perceptions on the Role of Pharmacists.

BACKGROUND:: Over the last decade, the pharmacists' role in health-care services has evolved and expanded to include more direct patient care and disease management services. OBJECTIVE:: To evaluate medical students' perceptions on pharmacists, their role in health care, and demographic or experiential factors that influenced the medical students' opinions. METHODS:: Medical students, at a Midwest, academic medical center, were solicited to complete a cross-sectional, web-based survey consisting of 3 domains: basic demographics, knowledge of the pharmacy profession, and opinions of pharmacists. RESULTS:: Participants supported pharmacists' role in recommending and monitoring drug therapy. However, participants did not support pharmacists' role in performing physical examinations, health screenings, or managing patients with chronic diseases. The main factors that influenced perceptions of pharmacists were female gender and frequent (weekly or more) interaction with a pharmacist or pharmacy student. Neither year in medical school nor participation in intercollaborative practice significantly influenced perceptions of pharmacists. CONCLUSION:: This survey highlights the need to improve the education medical students receive about pharmacists' contribution to the health-care team and the importance of increasing the interaction between medical students and pharmacists or pharmacy students to enhance interprofessional collaboration.

Middle Cerebral Artery Stroke as Amusement Park Injury: Case Report and Review of the Literature.

Strokes as amusement park injuries are rare, but have been reported in the literature. Only about 20 cases of cerebrovascular accidents after amusement park visits have been described. We report a healthy 12-year-old boy who presented with facial droop, slurred speech, and inability to use his right arm after riding roller coasters at a local amusement park. He was evaluated and found to have a left middle cerebral artery (MCA) infarction. The patient was treated with anticoagulants and has recovered with no major residual symptoms. It is likely that his neurological symptoms occurred due to the high head accelerations experienced on the roller coasters, which are more detrimental to children due to immature cervical spine development and muscle strength. Early diagnosis of dissection and stroke results in a favorable prognosis. Providers and parents should be aware of the potential risk of roller coasters and act quickly on neurologic changes in children that have recently been to an amusement park.

Clinical Interpretation of Urine Drug Tests: What Clinicians Need to Know About Urine Drug Screens.

Urine drug testing is frequently used in clinical, employment, educational, and legal settings and misinterpretation of test results can result in significant adverse consequences for the individual who is being tested. Advances in drug testing technology combined with a rise in the number of novel misused substances present challenges to clinicians to appropriately interpret urine drug test results. Authors searched PubMed and Google Scholar to identify published literature written in English between 1946 and 2016, using urine drug test, screen, false-positive, false-negative, abuse, and individual drugs of abuse as key words. Cited references were also used to identify the relevant literature. In this report, we review technical information related to detection methods of urine drug tests that are commonly used and provide an overview of false-positive/false-negative data for commonly misused substances in the following categories: cannabinoids, central nervous system (CNS) depressants, CNS stimulants, hallucinogens, designer drugs, and herbal drugs of abuse. We also present brief discussions of alcohol and tricyclic antidepressants as related to urine drug tests, for completeness. The goal of this review was to provide a useful tool for clinicians when interpreting urine drug test results and making appropriate clinical decisions on the basis of the information presented.

Psychotropic medication use in hospitalized patients with borderline personality disorder.

INTRODUCTION: Use of medications to treat symptoms of borderline personality disorder (BPD) is controversial. The purpose of this study was to describe psychotropic medication use in hospitalized patients with BPD and compare with a control group. METHODS: A retrospective chart review was conducted on hospitalized patients aged 18-65 years having a diagnosis of BPD and compared them with a control group of patients with a diagnosis of major depressive disorder (MDD) without a personality disorder. Patients were excluded from the BPD group if other personality disorders were recorded. Charts were reviewed for demographics and psychotropic medication usage both prior to admission and at discharge. RESULTS: This study included 165 patients (85 in BPD; 80 in MDD). Prior to admission and upon discharge, patients in the BPD group were prescribed significantly more psychotropic medications than patients with MDD (3.21 vs 2.10; P < .001 and 2.87 vs 2.35; P < .05, respectively). Patients in the BPD group were significantly more likely to be prescribed antipsychotics, mood stabilizers, and miscellaneous agents compared with the MDD group. On admission, significantly more BPD patients were prescribed multiple sedative agents (37.6% vs 21.3%; P < .05), but because of the discontinuation of sedative agents, this difference was nonsignificant upon discharge. DISCUSSION: This study found increased medication utilization among patients with BPD. Polypharmacy may increase the risk of side effects, drug interactions, and drug toxicity for BPD patients. Clinicians need to carefully evaluate the efficacy and risk of medications prescribed in patients with BPD.

Pharmacy Students' Knowledge and Attitudes Regarding Medical Marijuana.

OBJECTIVE: To determine pharmacy students' knowledge of and attitudes toward medical marijuana and to determine if pharmacy students need additional education on the topic. METHODS: Pharmacy students were asked to complete a survey on medical marijuana that assessed their knowledge of, medical uses of, adverse effects with, and attitudes toward medical marijuana through 23 Likert-scale questions. RESULTS: Three hundred eleven students completed the survey. Fifty-eight percent of the students felt that medical marijuana should be legalized in all states. However, the majority of students did not feel comfortable answering consumers' questions regarding efficacy, safety, or drug interactions related to the substance. Accurate responses for diseases or conditions for permitted medical marijuana use was low, with only cancer (91%) and glaucoma (57%) identified by more than half the students. CONCLUSION: With an increasing number of states adopting medical marijuana use, pharmacy schools need to evaluate the adequacy of medical marijuana education in their curriculum.

Pediatric Surfer's Myelopathy.

BACKGROUND: We present the case of the youngest known patient diagnosed with surfer's myelopathy. Surfer's myelopathy is a rare nontraumatic myelopathy. The most likely etiology, presumably, is arterial insufficiency related to spine hyperextension. Symptoms consist of back pain, urinary incontinence or retention, paraplegia, and sensory loss. CASE REPORT: A 7-year-old girl presented with back pain, urinary retention, and lower extremity weakness after doing backbends during a cheerleading practice the day prior to presentation. WHY SHOULD AN EMERGENCY MEDICINE PHYSICIAN BE AWARE OF THIS?: With the trend of children becoming increasingly active in competitive sports at a younger age, surfer's myelopathy is a diagnosis that should be considered when the symptoms are present and the history consists of hyperextending the back. As in our case, a seemingly benign trauma can lead to the diagnosis of surfer's myelopathy.

Angiocentric glioma with high proliferative index: case report and review of the literature.

With less than 50 cases previously reported in literature, angiocentric glioma (AG) is an uncommon, slow-growing tumor of the CNS that typically exhibits a low proliferative rate and is generally surgically curable. We report the case of a 3-year-old child who presented with seizures and was found to have a non-enhancing parietal lobe lesion with overlying calvarial remodeling. Following complete resection of the tumor, histopathological examination revealed bipolar spindle cells centered on cortical blood vessels, forming pseudorosettes with an ependymomatous appearance. Tumor cells were glial fibrillary acidic protein (GFAP) positive, yet failed to label with synaptophysin. Scattered tumor cells had a "dot-like" cytoplasmic staining with the antibody against epithelial membrane antigen (EMA). Collectively, these features favored a diagnosis of AG. Interestingly, the monoclonal antibody against Ki-67 (MIB-1) labeling rate averaged approximately 10.0%. The child continues to be tumor- and seizure-free ten months postoperatively. Long-term follow up is required to determine if the high proliferative rate observed in this AG translates into altered clinical behavior and/or a worse prognosis.