Emergency department utilization and disposition outcomes by pediatric patients with cancer in Maryland and New York from 2013 to 2017.

BACKGROUND: Pediatric patients with cancer commonly seek emergency department (ED) care, yet there is limited evidence on ED utilization patterns and disposition outcomes among these patients. METHODS: Retrospective analysis of the Healthcare Cost and Utilization Project State Emergency Department Databases and State Inpatient Databases for Maryland and New York from 2013 to 2017. We compared ED visits and disposition outcomes for 5.8 million pediatric patients (<18 years old) with and without cancer, and used multivariable regressions to estimate associations between the number of ED visits, hospital (inpatient) admissions through the ED, and ED or inpatient mortality and sociodemographic and clinical factors within the cancer cohort. RESULTS: Pediatric patients with cancer had more ED visits per year on average (2.4 vs. 1.5, p < .001), higher shares of admissions (56.8% vs. 6.6%, p < .001) and mortality (1.2% vs. 0.1%, p < .001) compared to those without cancer. Among patients with cancer, uninsured pediatric patients had fewer ED visits and lower risk of admission to a hospital through the ED compared to those with Medicaid coverage (total visits: incidence rate ratio [IRR]: 0.82, 95% confidence intervals [CI]: 0.75-0.90; admission: IRR: 0.75, 95% CI: 0.65-0.86). Mortality risks were higher for pediatric patients with cancer residing in areas with the lowest median household income, and with no health insurance coverage (IRR: 2.81, 95% CI: 1.21-6.51) compared to Medicaid. CONCLUSIONS: Our findings emphasize the importance of enhancing health insurance coverage policies and social services for pediatric patients with cancer and their families to address clinical and nonclinical needs.

Carfilzomib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma: A Phase I Trial.

INTRODUCTION: We designed a multicenter, phase Ib dose-escalation trial of carfilzomib with bendamustine and rituximab in patients with relapsed/refractory non-Hodgkin lymphoma (NCT02187133) in order to improve the response rates of this difficult-to-treat population. Chemoimmunotherapy with bendamustine and rituximab has shown activity in a variety of lymphomas, and proteasome inhibitors have demonstrated pre-clinical synergy and early clinical activity in this population. The objectives were to determine the maximum tolerated dose of carfilzomib and the preliminary efficacy of this combination. PATIENTS AND METHODS: The protocol followed a 3+3 design of carfilzomib dose escalation combined with standard doses of bendamustine and rituximab. Patients were treated for up to 6 cycles with an interim positron emission tomography/computed tomography after cycle 3. RESULTS: Ten patients were treated on the dose-escalation phase. The study was terminated at a carfilzomib dose of 56 mg/m2, and the maximum tolerated dose was not reached. The most common grade 3/4 adverse event was thrombocytopenia. There was 1 dose-limiting toxicity observed, grade 3 febrile neutropenia, and there were no treatment-related deaths. The overall response rate was 40% (complete response rate, 30%), with a median duration of response of 12 months and a median progression-free survival of 2.1 months. CONCLUSION: Carfilzomib in combination with bendamustine and rituximab is a safe and well-tolerated treatment for patients with relapsed/refractory non-Hodgkin lymphoma. Preliminary data indicate that this combination may have efficacy with an acceptable side effect profile in this heavily pre-treated patient population with limited treatment options.

Pediatric ingestions with gummy formulated medications: a retrospective study.

CONTEXT: Gummy formulations are widely available with estimated 65% marketed for children. Currently, there are few studies describing children ingesting gummy formulated medications. The aim of this study was to quantify and identify the type of ingestions due to gummy formulated medications, evaluate their clinical significance as defined by adverse outcomes: associated symptoms, emergency department (ED) visits, and hospitalizations. METHODS: Retrospective study in children aged 0-19 exposed to gummy formulated medications from 2015 to 2017 as identified by calls made to the Regional Poison Control Center (RPCC). A list of potentially toxic gummy formulated medications was compiled and reviewed by medical and clinical toxicologists. We categorized medications into vitamins, minerals and supplements, melatonin, and other. Data collected included: medication name, number of units, age, sex, symptoms described, ED visit, hospitalization, and unintentional or intentional ingestion. DISCUSSION: Of the 66,059 pediatric exposures received by RPCC, 1143 (1.7%) involved gummy formulated medications of which 1098 were analyzed. Median age was 3 years, 57.7% were males and 7% were symptomatic. Seventy-four percent exposures involved vitamins and 24% melatonin. In comparison to other gummy exposures, those who ingested melatonin had 8.4 times higher odds of being symptomatic (OR: 8.4, 95% CI: 5.1, 14) and 4.8 times higher odds of visiting ED (OR: 4.8, 95% CI: 2.5, 9). The predominant symptoms reported were drowsiness, gastrointestinal upset, and hyperactivity. Two patients were hospitalized who ingested multiple medications, one was unintentional, and one was intentional as a suicide attempt thus admitted for psychiatric stabilization. CONCLUSIONS: Gummy formulated medications comprised <2% of the total pediatric calls to the RPCC. Although, the occurrence of symptoms is rare, these medications especially those containing melatonin should be safely stored.

Somatic Symptoms of Anxiety and Suicide Ideation Among Treatment-Seeking Youth With Anxiety Disorders.

OBJECTIVE: The severity of anxiety, in general, has been associated with suicide ideation (SI) among youth, but research has yet to examine the specific anxiety symptoms that may contribute to SI among youth. This study examined the severity of specific anxiety symptom clusters (i.e., tense/restless, somatic/autonomic symptoms, humiliation/rejection, performing in public, separation anxiety, perfectionism, and anxious coping) and SI in youth who met diagnostic criteria for an anxiety disorder. METHOD: Participants (N = 87) were treatment-seeking children and adolescents ages 6-17 (M = 11.1 years, SD = 3.06; 52.9% male) diagnosed with a principal anxiety disorder. Youth and their parents completed measures of youth anxiety symptom severity, depression, and SI. RESULTS: Hierarchical linear regressions revealed that when anxiety symptom clusters were entered simultaneously, only youth self-reported (and not parent-reported) somatic/autonomic symptoms of anxiety significantly predicted SI, after controlling for depression and sex. Importantly, the relationship between somatic/autonomic symptoms of anxiety and SI was stronger than that between depression and SI. CONCLUSIONS: These results suggest that assessing somatic symptoms of anxiety is especially important when quantifying suicide risk among anxiety-disordered youth.

The Treatment of Anxiety in Autism Spectrum Disorder (TAASD) Study: Rationale, Design and Methods.

This paper describes the rationale, design, and methods of the Treatment for Anxiety in Autism Spectrum Disorders study, a three-site randomized controlled trial investigating the relative efficacy of a modular CBT protocol for anxiety in ASD (Behavioral Interventions for Anxiety in Children with Autism) versus standard CBT for pediatric anxiety (the Coping Cat program) and a treatment-as-usual control. The trial is distinct in its scope, its direct comparison of active treatments for anxiety in ASD, and its comprehensive approach to assessing anxiety difficulties in youth with ASD. The trial will evaluate the relative benefits of CBT for children with ASD and investigate potential moderators (ASD severity, anxiety presentation, comorbidity) and mediators of treatment response, essential steps for future dissemination and implementation.

Treatment Concerns and Functional Impairment in Pediatric Anxiety.

Although there are efficacious, evidence-based treatments for anxiety disorders, youth often experience delays in seeking therapy. Myriad reasons may contribute to this lag in treatment initiation, with some youth possessing concerns about therapy. Treatment concerns are broadly characterized by worries/ambivalence about seeking treatment, including concerns about the negative reactions, consequences, and inconvenience of treatment. As no studies exist for youth with anxiety disorders, this study examined the phenomenology of treatment concerns in 119 treatment-seeking, anxious youth and utilized a structural equation model to examine the relationship between child anxiety, depressive symptoms, treatment concerns, and anxiety-related functional impairment. Over 90 % of the children positively endorsed some type of treatment-related fear, with the most frequently expressed concern being that therapy would take too much time (50.4 %). Based on the model, both child anxiety and depressive symptoms predicted functional impairment, and treatment concerns mediated the relationship between child anxiety and functional impairment.

Adverse Prenatal, Perinatal and Neonatal Experiences in Children with Anxiety Disorders.

This study examined the incidence of adverse prenatal, perinatal, and neonatal experiences amongst children with anxiety disorders, and the relationship to clinical symptomology and functional impairment in treatment-seeking children (N = 107) with a primary anxiety disorder. Anxious children had higher rates of reported maternal prescription medication use during pregnancy, maternal smoking and illness during pregnancy and neonatal complications (including neonatal intensive care and feeding issues) compared with population base rates and non-affected children. Almost one-third had early problems with sleep. Developmental problems were common with more than half having at least one area of delay. More than three quarters of anxious children had a first-degree family member with a psychiatric history. There were several associations between neonatal complications and subsequent clinical symptomology, including attention deficit hyperactivity disorder and depressive comorbidity, anxiety severity and functional impairment. Findings suggest higher rates of perinatal complications in anxious children.

A RANDOMIZED CONTROLLED TRIAL IN COMMUNITY MENTAL HEALTH CENTERS OF COMPUTER-ASSISTED COGNITIVE BEHAVIORAL THERAPY VERSUS TREATMENT AS USUAL FOR CHILDREN WITH ANXIETY.

OBJECTIVE: This study aims to examine the real-world effectiveness of a computer-assisted cognitive behavioral therapy (CBT) protocol relative to treatment as usual (TAU) among anxious children presenting at community mental health centers. METHODS: One hundred children (7-13 years) with clinically significant anxiety were randomized to receive either 12 weekly computer-assisted CBT sessions or TAU for an equivalent duration. Assessments were conducted by independent evaluators at screening/baseline, midtreatment, posttreatment, and 1-month followup (for computer-assisted CBT treatment responders). RESULTS: There were significant between-group effects favoring the computer-assisted CBT condition on primary anxiety outcomes. Thirty of 49 (61.2%) children randomized to computer-assisted CBT responded to treatment, which was superior to TAU (6/51, 11.8%). Relative to TAU, computer-assisted CBT was associated with greater reductions in parent-rated child impairment and internalizing symptoms, but not child-rated impairment and anxiety and depressive symptoms. Treatment satisfaction and therapeutic alliance in those receiving computer-assisted CBT was high. Treatment gains in computer-assisted CBT responders were maintained at 1-month followup. CONCLUSIONS: Within the limitations of this study, computer-assisted CBT is an effective and feasible treatment for anxious children when used in community mental health centers by CBT-naïve clinicians.

Clinical characteristics and predictors of hoarding in children with anxiety disorders.

OBJECTIVE: This investigation was conducted to describe the clinical of characteristics of anxious children with significant hoarding behavior and to examine the contributions of anxiety, obsessive compulsive, and inattentive and hyperactive/impulsive symptoms in the prediction of hoarding. METHOD: One hundred nine children seeking treatment for an anxiety disorder and their parents completed clinician-administered and parent-report measures of emotional and behavioral symptoms, functional impairment, and hoarding symptoms. RESULTS: Elevated levels of hoarding were reported for 22% of the sample. Children with elevated hoarding scored significantly higher on measures of anxiety, obsessive-compulsive, attention, social, and thought problems, rule-breaking, aggression, and overall functional impairment and had higher rates of major depressive disorder than children without hoarding. Attention problems predicted hoarding symptomology over-and-above the contributions of either anxiety or obsessive-compulsive symptoms. CONCLUSIONS: Findings suggest a pattern of behavioral and emotional dysregulation for children who hoard and provide further insight into the relationships between anxiety, attention problems, and hoarding.

Phenomenology and clinical correlates of family accommodation in pediatric anxiety disorders.

Despite evidence documenting high prevalence of family accommodation in pediatric obsessive-compulsive disorder, examination in other pediatric anxiety disorders is limited. Preliminary evidence suggests that family accommodation is common amongst children with anxiety disorders; however, the impact on clinical presentation and functional impairment has not been addressed. This study assessed the nature and clinical correlates of family accommodation in pediatric anxiety, as well as validating a mechanistic model. Participants included 112 anxious youth and their parents who were administered a diagnostic clinical interview and measure of anxiety severity, as well as questionnaires assessing internalizing and externalizing symptoms, family accommodation and functional impairment. Some form of accommodation was present in all families. Family accommodation was associated with increased anxiety severity and externalizing behaviors, having a diagnosis of separation anxiety, and increased functional impairment. Family accommodation partially mediated the relationship between anxiety severity and functional impairment, as well as externalizing behaviors and functional impairment. Family accommodation is common in pediatric anxiety disorders, and is associated with more severe clinical presentations and functional impairment. These findings highlight the importance of parental involvement in treatment and the need to specifically target accommodation practices during interventions to mitigate negative outcomes in anxious youth. Further studies utilizing longitudinal data are needed to validate mechanistic models.

Incidence, clinical correlates and treatment effect of rage in anxious children.

Episodic rage represents an important and underappreciated clinical feature in pediatric anxiety. This study examined the incidence and clinical correlates of rage in children with anxiety disorders. Change in rage during treatment for anxiety was also examined. Participants consisted of 107 children diagnosed with an anxiety disorder and their parents. Participants completed structured clinical interviews and questionnaire measures to assess rage, anxiety, functional impairment, family accommodation and caregiver strain, as well as the quality of the child's relationship with family and peers. Rage was a common feature amongst children with anxiety disorders. Rage was associated with a more severe clinical profile, including increased anxiety severity, functional impairment, family accommodation and caregiver strain, as well as poorer relationships with parents, siblings, extended family and peers. Rage was more common in children with separation anxiety, comorbid anxiety, attention deficit/hyperactivity disorder and behavioral disorders, but not depressive symptoms. Rage predicted higher levels of functional impairment, beyond the effect of anxiety severity. Rage severity reduced over treatment in line with changes in anxiety symptoms. Findings suggest that rage is a marker of greater psychopathology in anxious youth. Standard cognitive behavioral treatment for anxiety appears to reduce rage without adjunctive treatment.

Determining trace amounts and the origin of formaldehyde impurity in Neisseria meningitidis A/C/Y/W-135-DT conjugate vaccine formulated in isotonic aqueous 1× PBS by improved C18-UPLC method.

The ability to accurately measure and report trace amounts of residual formaldehyde impurity in a vaccine product is not only critical in the product release but also a regulatory requirement. In many bacterial or viral vaccine manufacturing procedures, formaldehyde is used either at a live culture inactivation step or at a protein de-toxification step or at both. Reported here is a validated and improved C18-UPLC method (developed based on previously published C-8 HPLC method) to determine the traces of formaldehyde process impurity in a liquid form Neisseria meningitidis A/C/Y/W-135-DT conjugate vaccine formulated in isotonic aqueous 1× PBS. UPLC C-18 column and the conditions described distinctly resolved the 2,4-DNPH-HCHO adduct from the un-reacted 2,4-DNPH as detected by TUV detector at 360 nm. This method was shown to be compatible with PBS formulation and extremely sensitive (with a quantitation limit of 0.05 ppm) and aided to determine formaldehyde contamination sources by evaluating the in-process materials as a track-down analysis. Final nanogram levels of formaldehyde in the formulated single dose vialed vaccine mainly originated from the diphtheria toxoid carrier protein used in the production of the conjugate vaccine, whereas relative contribution from polysaccharide API was minimal.

Frequency and correlates of suicidal ideation in pediatric obsessive-compulsive disorder.

This study examined the frequency and sociodemographic and clinical correlates of suicidal ideation in a sample of children and adolescents with obsessive-compulsive disorder (OCD). Fifty-four youth with OCD and their parent(s) were administered the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime, Children's Yale-Brown Obsessive Compulsive Scale, and Children's Depression Rating Scale-Revised. Children completed the Suicidal Ideation Questionnaire-Junior (SIQ-JR), Child Obsessive Compulsive Impact Scale-Child, and Multidimensional Anxiety Scale for Children; parents completed the Child Obsessive Compulsive Impact Scale-Parent, Swanson, Nolan, and Pelham-IV Parent Scale, and Young Mania Rating Scale-Parent Version. Seven youth endorsed clinically significant levels of suicidal ideation on the SIQ-JR. Suicidal ideation was significantly related to clinician-rated depressive symptoms, age, child-rated impairment and anxiety symptoms, and symmetry, sexuality/religiosity and miscellaneous symptom dimensions. There was no significant association between suicidal ideation and obsessive-compulsive symptom severity, comorbidity patterns, or several parent-rated indices (e.g., impairment, impulsivity). These results provide initial information regarding the frequency and correlates of suicidal ideation in treatment-seeking youth with OCD. Clinical implications are discussed, as well as directions for future research.

Consumers' and providers' perceptions of utilizing a computer-assisted cognitive behavioral therapy for childhood anxiety.

BACKGROUND: Computer-assisted cognitive behavioral therapy (CCBT) programs for childhood anxiety are being developed, although research about factors that contribute to implementation of CCBT in community mental health centers (CMHC) is limited. AIM: The purpose of this mixed-methods study was to explore consumers' and providers' perceptions of utilizing a CCBT for childhood anxiety in CMHC in an effort to identify factors that may impact implementation of CCBT in CMHC. METHOD: Focus groups and interviews occurred with 7 parents, 6 children, 3 therapists, 3 project coordinators and 3 administrators who had participated in CCBT for childhood anxiety. Surveys of treatment satisfaction and treatment barriers were administered to consumers. RESULTS: RESULTS suggest that both consumers and providers were highly receptive to participation in and implementation of CCBT in CMHC. Implementation themes included positive receptiveness, factors related to therapists, treatment components, applicability of treatment, treatment content, initial implementation challenges, resources, dedicated staff, support, outreach, opportunities with the CMHC, payment, and treatment availability. CONCLUSION: As studies continue to demonstrate the effectiveness of CCBT for childhood anxiety, research needs to continue to examine factors that contribute to the successful implementation of such treatments in CMHC.

Quantification of each serogroup polysaccharide of Neisseria meningitidis in A/C/Y/W-135-DT conjugate vaccine by high-performance anion-exchange chromatography-pulsed amperometric detection analysis.

Invasive bacterial meningitis caused by Neisseria meningitidis can be prevented by active immunization with meningococcal polysaccharide or polysaccharide-protein conjugate vaccines. In a tetravalent A/C/Y/W-135-DT meningococcal conjugate vaccine vial, or in a final formulated bulk, accurate identification and quantification of each polysaccharide are critical in product release. Determination of sialic acid serogroups (C, W-135, and Y) unambiguously is complex since all these serogroups contribute to the sialic acid monosaccharide peaks that overlap in the high-performance anion-exchange chromatography-pulsed amperometric detection (HPAEC-PAD). We report a quantification method that involves generation of monosaccharide standard plots for respective sugars mannosamine-6-phosphate, sialic acid, galactose- and glucose-derived from hydrolysis of mixtures of the four serogroups A, C, W, and Y reference polysaccharides. These plots were then used to obtain the unknown polysaccharide concentrations of A/C/Y/W-135 in vialed vaccine or from formulated final bulks. We also present our results of the HPAEC-PAD profiles on groups C, W-135, and Y polysaccharides when hydrolyzed individually and/or in mixtures to discuss the individual sialic acid peak contributions.

Family-based exposure and response prevention therapy for preschool-aged children with obsessive-compulsive disorder: a pilot randomized controlled trial.

AIMS: To examine the feasibility, acceptability and preliminary efficacy of family-based exposure/response prevention therapy (E/RP) versus treatment as usual (TAU) in a cohort of very young children with early onset obsessive-compulsive disorder (OCD). METHODS: Thirty-one children ages 3-8 years (M = 5.8 years) with a primary diagnosis of OCD were randomized to E/RP or TAU. The E/RP condition received 12 sessions of family-based E/RP twice weekly over 6 weeks. Families were assessed at baseline, post-treatment, 1-month and 3-month follow up. The Children's Yale Brown Obsessive Compulsive Scale and Clinical Global Impression served as primary outcome measures. RESULTS: A large group effect emerged in favor of the E/RP group (d = 1.69). Sixty-five percent of the E/RP group was considered treatment responders as compared to 7% in the TAU group. Symptom remission was achieved in 35.2% of the E/RP group and 0% of the TAU group. There was no attrition and satisfaction was high; gains were maintained at 3 months. CONCLUSIONS: Even amongst children as young as 3 years, developmentally tailored E/RP is efficacious and well-tolerated in reducing OCD symptoms. Key adaptations for younger children include extensive parent involvement, targeting family accommodation, and frequent meetings while delivering a full course of E/RP. CLINICALTRIALSGOV IDENTIFIER: NCT01447966 http://clinicaltrials.gov/ct2/show/NCT01447966?term=ocd+and+st+petersburg&rank=1.

Neuropsychological performance across symptom dimensions in pediatric obsessive compulsive disorder.

BACKGROUND: Few studies have examined neuropsychological functioning among youth with obsessive compulsive disorder (OCD), with inconclusive results. Although methodological differences may contribute to inconsistent findings, clinical factors may also account for differential performance. Symptom dimensions are associated with specific patterns of genetic transmission, comorbidity, and treatment outcome, and may also be uniquely associated with neuropsychological performance. This study examined differences in cognitive sequelae and neurocognitive impairment across symptom dimensions among youth with OCD. METHOD: Participants included 93 treatment-seeking youth diagnosed with OCD. A trained clinician administered the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) to parents and children together. Afterward, youth completed a battery of neuropsychological tests that assessed nonverbal memory and fluency, verbal memory, verbal fluency, verbal learning, processing speed, and inhibition/switching. RESULTS: Across five symptom dimensions, youth exhibiting Hoarding symptoms (χ(2) = 5.21, P = .02) and Symmetry/Ordering symptoms had a greater occurrence of cognitive sequelae (χ(2) = 4.86, P = .03). Additionally, youth with Symmetry/Ordering symptoms had a greater magnitude of cognitive impairment (Mann-Whitney U = 442.50, Z = -2.49, P < .02), with specific deficits identified on nonverbal fluency (P < .01), processing speed (P < .01), and inhibition and switching (P < .02). CONCLUSIONS: Neuropsychological deficits identified in youth with Hoarding and Symmetry/Ordering symptoms may suggest that these symptoms have characteristics specific to neurocognitive impairment. Alternatively, symptoms associated with these dimensions may impede youth's performance during testing. Findings advise neuropsychological testing for youth with symptoms on either of these dimensions when concerns about neuropsychological and/or academic impairment are present.

Mediators and moderators of functional impairment in adults with obsessive-compulsive disorder.

The current study examined correlates, moderators, and mediators of functional impairment in 98 treatment-seeking adults with obsessive-compulsive disorder (OCD). Participants completed or were administered measures assessing obsessive-compulsive symptom severity, functional impairment, resistance against symptoms, interference due to obsessive-compulsive symptoms, depressive symptoms, insight, and anxiety sensitivity. Results indicated that all factors, except insight into symptoms, were significantly correlated with functional impairment. The relationship between obsessive-compulsive symptom severity and functional impairment was not moderated by patient insight, resistance against obsessive-compulsive symptoms, or anxiety sensitivity. Mediational analyses indicated that obsessive-compulsive symptom severity mediated the relationship between anxiety sensitivity and obsessive-compulsive related impairment. Indeed, anxiety sensitivity may play an important contributory role in exacerbating impairment through increases in obsessive-compulsive symptom severity. Depressive symptoms mediated the relationship between obsessive-compulsive symptom severity and obsessive-compulsive related impairment. Implications for assessment and treatment are discussed.

A Pilot Study of Computer-Assisted Cognitive Behavioral Therapy for Childhood Anxiety in Community Mental Health Centers.

Anxiety disorders among children are common, disabling, and run a chronic course without treatment. Cognitive behavioral therapy (CBT) has shown robust efficacy for childhood anxiety. However, dissemination of CBT into community mental health centers (CMHCs) is limited. Computer-assisted CBT (CCBT) programs have been developed to improve dissemination by providing a structured treatment format that allows therapists to reliably deliver evidence-based treatments with fidelity. In this pilot study involving therapists with limited CBT experience, the effectiveness, feasibility, and acceptability of a CCBT program, Camp Cope-A-Lot (Khanna & Kendall, 2008b), were examined in three CMHCs. Seventeen youth ages 7-13 years and diagnosed with a primary anxiety disorder were enrolled. Assessments were conducted by a rater not involved in treatment at baseline and posttreatment. Significant reductions in anxiety severity and impairment were demonstrated at the posttreatment assessment. High levels of family satisfaction were reported. These results provide preliminary support for the effectiveness of a computer-assisted treatment into CMHCs and warrant replication in a controlled setting.