Pharmacological Intervention in Children with Autism Spectrum Disorder with Standard Supportive Therapies Significantly Improves Core Signs and Symptoms: A Single-Center, Retrospective Case Series

Purpose: Autism spectrum disorder (ASD) is a debilitating neurodevelopmental disorder with high heterogeneity and no clear common cause. Several drugs, in particular risperidone and aripiprazole, are used to treat comorbid challenging behaviors in children with ASD. Treatment with risperidone and aripiprazole is currently recommended by the Food and Drug Administration (FDA) in the USA for children aged 5 and 6 years and older, respectively. Here, we investigated the use of these medications in younger patients aged 4 years and older. Patients and Methods: This retrospective case series included 18 children (mean age, 5.7 years) with ASD treated at the Kids Neuro Clinic and Rehab Center in Dubai. These patients began treatment with risperidone or aripiprazole at the age of 4 years and older, and all patients presented with comorbid challenging behaviors that warranted pharmacological intervention with either risperidone or aripiprazole. Results: All 18 children showed objective improvement in their ASD core signs and symptoms. Significant improvement was observed in 44% of the cases, and complete resolution (minimal-to-no-symptoms) was observed in 56% of the cases as per the Childhood Autism Rating Scale 2-Standard Test (CARS2-ST) and the Clinical Global Impression (CGI) scales. Conclusion: Our findings indicate that the chronic administration of antipsychotic medications with or without ADHD medications is well tolerated and efficacious in the treatment of ASD core and comorbid symptoms in younger children when combined with standard supportive therapies. This is the first report to suggest a treatment approach that may completely resolve the core signs and symptoms of ASD. While the reported outcomes indicate significant improvement to complete resolution of ASD, pharmacological intervention should continue to be considered as part of a multi-component intervention in combination with standard supportive therapies. Furthermore, the findings support the critical need for double-blind, placebo-controlled studies to validate the outcomes

Epidemic Leptospirosis Associated with Pulmonary Hemorrhage—Nicaragua, 1995

In October 1995, epidemic “hemorrhagic fever,” without jaundice or renal manifestations, was reported in rural Nicaragua following heavy flooding; 2259 residents were evaluated for nonmalarial febrile illnesses (cumulative incidence, 6.1%) and 15 (0.7%) died with pulmonary hemorrhage. A case-control study found that case-patients were more likely than controls to have ever walked in creeks (matched odds ratio [MOR], 15.0; 95% confidence interval [CI], 1.7–132.3), have household rodents (MOR, 10.4; 95% CI, 1.1–97.1), or own dogs with titers ≥ 400 to Leptospira species (MOR, 23.4; 95% CI, 3.6–`). Twenty-six of 51 case-patients had serologic or postmortem evidence of acute leptospirosis. Leptospira species were isolated from case-patients and potential animal reservoirs. This leptospirosis epidemic likely resulted from exposure to flood waters contaminated by urine from infected animals, particularly dogs. Leptospirosis should be included in the differential diagnosis for nonmalarial febrile illness, particularly during periods of flooding or when pulmonary hemorrhage occurs

Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients

Background: CLN2 disease (Neuronal Ceroid Lipofuscinosis Type 2) is an ultra-rare, neurodegenerative lysosomal storage disease, caused by an enzyme deficiency of tripeptidyl peptidase 1 (TPP1). Lack of disease awareness and the non-specificity of presenting symptoms often leads to delayed diagnosis. These guidelines provide robust evidence-based, expert-agreed recommendations on the risks/benefits of disease-modifying treatments and the medical interventions used to manage this condition. Methods: An expert mapping tool process was developed ranking multidisciplinary professionals, with knowledge of CLN2 disease, diagnostic or management experience of CLN2 disease, or family support professionals. Individuals were sequentially approached to identify two chairs, ensuring that the process was transparent and unbiased. A systematic literature review of published evidence using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance was independently and simultaneously conducted to develop key statements based upon the strength of the publications. Clinical care statements formed the basis of an international modified Delphi consensus determination process using the virtual meeting (Within3) online platform which requested experts to agree or disagree with any changes. Statements reaching the consensus mark became the guiding statements within this manuscript, which were subsequently assessed against the Appraisal of Guidelines for Research and Evaluation (AGREEII) criteria. Results: Twenty-one international experts from 7 different specialities, including a patient advocate, were identified. Fifty-three guideline statements were developed covering 13 domains: General Description and Statements, Diagnostics, Clinical Recommendations and Management, Assessments, Interventions and Treatment, Additional Care Considerations, Social Care Considerations, Pain Management, Epilepsy / Seizures, Nutritional Care Interventions, Respiratory Health, Sleep and Rest, and End of Life Care. Consensus was reached after a single round of voting, with one exception which was revised, and agreed by 100% of the SC and achieved 80% consensus in the second voting round. The overall AGREE II assessment score obtained for the development of the guidelines was 5.7 (where 1 represents the lowest quality, and 7 represents the highest quality). Conclusion: This program provides robust evidence- and consensus-driven guidelines that can be used by all healthcare professionals involved in the management of patients with CLN2 disease and other neurodegenerative disorders. This addresses the clinical need to complement other information available

Graphical Representations of Adolescents' Psychophysiological Reactivity to Social Stressor Tasks: Reliability and Validity of the Chernoff Face Approach and Person-Centered Profiles for Clinical Use

Low-cost methods exist for measuring physiology when clinically assessing adolescent social anxiety. Two barriers to widespread use involve lack of (a) physiological expertise among mental health professionals, and (b) techniques for modeling individual-level physiological profiles. We require a "bridge approach" for interpreting physiology that does not require users to have a physiological background to make judgments, and is amenable to developing individual-level physiological profiles. One method-Chernoff Faces-involves graphically representing data using human facial features (eyes, nose, mouth, face shape), thus capitalizing on humans' abilities to detect even subtle variations among facial features. We examined 327 adolescents from the Tracking Adolescents' Individual Lives Survey (TRAILS) study who completed baseline social anxiety self-reports and physiological assessments within the social scenarios of the Groningen Social Stressor Task (GSST). Using heart rate (HR) norms and Chernoff Faces, 2 naive coders made judgments about graphically represented HR data and HR norms. For each adolescent, coders made 4 judgments about the features of 2 Chernoff Faces: (a) HR within the GSST and (b) aged-matched HR norms. Coders' judgments reliably and accurately identified elevated HR relative to norms. Using latent class analyses, we identified 3 profiles of Chernoff Face judgments: (a) consistently below HR norms across scenarios (n = 193); (b) above HR norms mainly when speech making (n = 35); or (c) consistently above HR norms across scenarios (n = 99). Chernoff Face judgments displayed validity evidence in relation to self-reported social anxiety and resting HR variability. This study has important implications for implementing physiology within adolescent social anxiety assessments

All Anxiety is not Created Equal: Correlates of Parent/Youth Agreement Vary Across Subtypes of Anxiety

Research has examined patterns and correlates of parent/youth informant discrepancies in the reporting of youth anxiety. However, little work has examined whether it is better to conceptualize patterns and correlates of informant disagreement across anxiety broadly, or more useful to consider disagreement on specific symptom clusters. Using data from the Child Adolescent/Anxiety Multimodal Study (CAMS; N = 488; Walkup et al., 2008), the current study applied the most recent recommended analytic strategies to study informant discrepancies and examined differences in the magnitude and patterns of disagreement for: (a) broadband anxiety symptoms, versus (b) symptoms of specific anxiety diagnoses (or anxiety subtypes; e.g., separation, social anxiety). Correlates of informant discrepancies were also examined. Results indicated that there was variability in agreement across anxiety subtypes, with parent/youth agreement higher on separation anxiety and school refusal symptoms relative to other domains. Parental psychopathology was associated with disagreement on broadband anxiety symptoms, such that parental psychopathology was highest when parents reported higher symptoms than their children; however, this finding was largely driven by a relationship between parental psychopathology and disagreement on separation anxiety symptoms. Age was associated with disagreement on total and separation anxiety symptoms. Gender was not associated with disagreement. Clinical implications are discussed