Reading comprehension improvement in autism.

Introduction: A subset of autistic children excel at word decoding but have difficulty with reading comprehension (i.e., the discrepant poor comprehender reading profile). Prior research suggests the Visualizing and Verbalizing (V/V) for language comprehension and thinking intervention helps improve reading comprehension in autistic children with this reading profile. Previous studies have demonstrated the role of vocabulary, memory, and social functioning in reading comprehension; however, predictors and moderators of reading comprehension within this specific profile of autistic readers have not been thoroughly explored. Methods: In this study, we examined the effectiveness of the V/V intervention by comparing reading comprehension scores between groups and across time. Participants included a sample of autistic children (AUT-EXP; n=22) and a waitlist control group of autistic children (AUT-WLC; n=17) with reading comprehension difficulties, as well as a sample of non-autistic children (Non-AUT; n=26) (all age 8-13 years). AUT-EXP and AUT-WLC groups completed a battery of cognitive assessments during pre and post tests. We also analyzed whether cognitive assessment scores predicted reading comprehension, and examined the moderating effects of group (AUT-EXP vs. AUT-WLC) on these relationships. Results: The AUT-EXP group significantly improved in their pre to post reading comprehension scores (t(21)=4.19, p<.001, d=.89), whereas the AUT-WLC group did not. Verbal memory significantly predicted reading comprehension, though group did not moderate relationships between cognitive test performance and reading comprehension. Discussion: Results suggest that the V/V intervention may help improve reading comprehension for autistic children with the discrepant poor comprehender reading profile. Additionally, strategies for improving verbal memory may indirectly enhance reading comprehension in autistic children with this reading profile.

Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial.

OBJECTIVE: This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age. METHODS: A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin. RESULTS: Of 84 infants enrolled, 12 were screen failures, 4 went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). Fifty-six were randomized to early vigabatrin (n = 29) or placebo (n = 27). Nineteen of 27 in the placebo arm transitioned to open label vigabatrin, with a median delay of 44 days after randomization. Bayley-III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug-resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups. INTERPRETATION: Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children, nor does it delay onset or lower the incidence of focal seizures and drug-resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms. ANN NEUROL 2023.

Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus in Children.

BACKGROUND AND OBJECTIVES: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children. METHODS: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort. We explored clinical variables that could be acquired early after presentation to emergency medical services with univariate analysis of the raw data. Variables with p < 0.1 were retained for univariable and multivariable regression analyses. Multivariable logistic regression models were fit to age-matched and sex-matched data to obtain variables associated with RSE. RESULTS: We compared data from a total of 595 episodes of pediatric SE. Univariate analysis demonstrated no differences in time to the first BZD (RSE 16 minutes [IQR 5-45]; rESE 18 minutes [IQR 6-44], p = 0.068). Time to second-line ASM was shorter in patients with RSE (RSE 65 minutes; rESE 70 minutes; p = 0.021). Both univariable and multivariable regression analyses revealed a family history of seizures (OR 0.37; 95% CI 0.20-0.70, p = 0.0022) or a prescription for rectal diazepam (OR 0.21; 95% CI 0.078-0.53, p = 0.0012) was associated with decreased odds of RSE. DISCUSSION: Time to initial BZD or second-line ASM was not associated with progression to RSE in our cohort of patients with rESE. A family history of seizures and a prescription for rectal diazepam were associated with a decreased likelihood of progression to RSE. Early attainment of these variables may help care for pediatric rESE in a more patient-tailored manner. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patient and clinical factors may predict RSE in children with convulsive seizures.

Happily Distant or Bitter Medicine? The Impact of Social Distancing Preferences, Behavior, and Emotional Costs on Subjective Wellbeing During the Epidemic.

To inhibit the spread of COVID-19 Public health officials stress, and governments often require, restrictions on social interaction ("social distancing"). While the medical benefits are clear, important questions remain about these measures' downsides: How bitter is this medicine? Ten large non-probability internet-based surveys between April and November 2020, weighted statistically to reflect the US population in age, education, and religious background and excluding respondents who even occasionally role-played rather than giving their own true views; N = 6,223. Pre-epidemic data from 2017-2019, N = 4,032. Reliable multiple-item scales including subjective wellbeing (2 European Quality of Life Survey items, Cronbach's alpha = .85); distancing attitudes (5 items, alpha = .87); distancing behavior e.g., standing 6' apart in public (5 items, alpha = .80); emotional cost of distancing and restrictions on social interaction (8-12 items, alpha = .94); and an extensive suite of controls (19 variables). Descriptive statistics, OLS regression, structural equation models. Subjective wellbeing is greater for those who approve of distancing, for those who practice distancing, and particularly for those whose distancing attitudes and behavior are congruent, either both in favor or both opposed (multiplicative interaction). The emotional cost of distancing is strongly tied to wellbeing and is heterogeneous, with some disliking distancing much more than others. An SEM model suggests causality: that emotional costs strongly reduce wellbeing but not vice-versa. During the epidemic, COVID issues constitute two of the top 5 influences on wellbeing, behind only subjective health and religious belief and tied with income. All this is net of family background, religious origins, age, ethnicity, race, gender, rural residence, education, occupational status, marriage, unemployment, income, health, religion, and political party. Supplementary Information: The online version contains supplementary material available at 10.1007/s11482-023-10149-0.

Evaluation of the Simplified Score to Predict Early Relapse in Multiple Myeloma (S-ERMM) in the MMRF CoMMpass study.

BACKGROUND: Zaccaria and colleagues recently proposed a new risk score to identify patients at high risk for relapse within 18 months of diagnosis (ER18), the Score for Early Relapse in Multiple Myeloma (S-ERMM). We performed external validation of the S-ERMM using data from the CoMMpass study. PATIENTS AND METHODS: Clinical data was obtained from the CoMMpass study. Patients were assigned S-ERMM risk scores and risk categories by the three iterations of the International Staging System (ISS): ISS, R-ISS and R2-ISS. Patients with missing data or early mortality in remission were excluded. Our primary endpoint was the relative predictive ability of the S-ERMM versus other risk scores for ER18 as assessed by area-under-the-curve (AUC). RESULTS: 476 patients had adequate data to assign all four risk scores. 65%, 25% and 10% were low, intermediate and high risk by S-ERMM. 17% experienced ER18. All four risk scores stratified patients by risk for ER18. S-ERMM (AUC: 0.59 [95% CI 0.53-0.65]) was similar to R-ISS (0.63 [95% CI 0.58-0.69]) and statistically inferior to ISS (0.68 [95% CI 0.62-0.75]) and R2-ISS (0.66 [95% CI 0.61-0.72]) for prediction of ER18. Sensitivity analyses were performed and did not significantly impact results. CONCLUSION: The S-ERMM risk score is not superior to existing risk stratification systems for predicting early relapse in NDMM and further studies are needed to identify the optimal approach.

Effect of Co-occurring Psychiatric Disorders on Treatment of Children with Autism Spectrum Disorder and Anxiety.

Co-occurring psychiatric diagnoses are very common in individuals with ASD. Little is known about the effect that co-occurring psychiatric conditions may have on treatment response to CBT for children with ASD and anxiety. The present study examined the relationship between co-occurring psychiatric diagnoses and response to CBT for anxiety in ninety youth with ASD. Psychiatric complexity did not appear to differentially impact treatment response. A notable portion of youth with anxiety and externalizing disorders such as ADHD, no longer met criteria for those externalizing diagnoses following intervention. Results indicate that youth with ASD and anxiety present with complex psychiatric profiles and CBT for anxiety may positively affect co-occurring diagnoses. In addition, thorough and nuanced assessment of psychiatric symptoms in youth with ASD is needed to ensure the differentiation between diagnoses of anxiety and other co-occurring psychiatric symptoms.

Classifying children with ASD by service utilization and treatment type: A cluster analysis of a nationally representative United States survey.

BACKGROUND: If there are patterns of the distribution of services and treatments across the population of people with ASD, these patterns should be based along clinical characteristics or other service needs and not sociodemographic characteristics unrelated to evidence-based care. We examined how individuals in a broad, nationally representative sample "grouped together" based on service utilization and services needed but not covered by insurance. By understanding various treatment patterns, clinicians, researchers, policymakers, and self-advocates and their families can better advocate for high-quality, evidence-based services to be provided equitably. METHODS: Using the 2011 Survey of Pathways to Diagnosis and Services, a cluster analysis was performed to explore patterns in this population based on medication use, private services use, school-based service use, and services not covered by insurance. Differences in clusters were then explored through multinomial logistic regression. RESULTS: Six clusters emerged, showing differences in the level of service/medication usage and insurance coverage. Differences across clusters were associated with the level of functional limitation and age at ASD diagnosis. Disparities by insurance type, functional limitation, and age at diagnosis exist among patterns of ASD service provision. CONCLUSIONS: Our analysis showed that intervention for children with ASD can be across several scales - high and low users of services (both private and school-based), high and low users of medications, and high and low levels of reported non-covered services. The differences were clustered in multiple ways. Further research should incorporate longitudinal and nationally representative data to explore these relationships further.

Pathways to Suicidal Behavior in Children and Adolescents: Examination of Child Maltreatment and Post-Traumatic Symptoms.

Suicide in youth exacts significant personal and community costs. Thus, it is important to understand predisposing risk factors. Experiencing adverse childhood experiences (ACEs), such as child maltreatment (CM-ACE), and the presence of post-traumatic stress disorder has been identified as a risk factor of suicidal behaviors among adults. Theoretical models of suicide suggest that the presence of painful experiences such as CM-ACEs increase the risk of suicidal behaviors. The relation between child maltreatment, post-traumatic stress symptom clusters (PTSS) and suicidal behaviors has not been explicitly examined among youth. The present study examined the relations between CM-ACEs, PTSS clusters, and suicidal behaviors in a clinical population of children. Children, male, ages 6 to 14, enrolled in a residential treatment program completed self-report measures to evaluate variables of interest. Path analyses revealed statistically significant direct effects of CM-ACEs and PTSS clusters on suicidal behaviors. Significant total indirect effects and marginally significant individual indirect effects of intrusion and avoidance symptoms were observed for the relation between CM-ACEs and suicidal behavior. Findings suggest that symptoms associated with specific PTSS clusters might help explain the relation between CM-ACEs and suicidal behavior, and therefore, present important implications for clinical practice and future research.

Influence of endocrine multidisciplinary tumor board on patient management and treatment decision making.

BACKGROUND: Multidisciplinary Tumor Boards (MDT) are used to obtain input regarding cancer management. This study assessed the impact of our institutional Endocrine MDT. METHODS: MDT notes on patients with thyroid cancer treated during 2012-2018 were abstracted retrospectively from the electronic medical record. Management change (MC) was prospectively collected by the MDT coordinator. Biannual evaluations reviewed the impact of the MDT as observed by attendees. RESULTS: MC was recommended in 47 (15%) of 286 presentations, with additional imaging being the most frequent (43%). Presentation of recurrences were more likely to result in MC (24% vs. 13% initial, p = 0.03). Overall, 98% of attendees found the conference exceeded educational expectations. About 24% reported intending to use a more evidence/guideline-based approach after attending and this trend increased over time (p = 0.002). CONCLUSION: MDT presentations led to a higher rate of MC particularly in recurrent TC patients and increased evidenced-based practice for attendees.

Organic Host Encapsulation Effects on Nitrosobenzene Monomer-Dimer Distribution and C-NO Bond Rotation in an Aqueous Solution.

The intermolecular (monomer-dimer equilibrium) and intramolecular (C-NO and C-NMe2 rotations) dynamics of 4-nitrosocumene (1a) and 4-(N,N-dimethylamino)nitrosobenzene (1b), respectively, were found to be controlled by the medium (water) and the host environment (organic capsules and cavitands). The ability of water to shift the equilibrium toward the dimer appears to result from dipolar stabilization of the polar dimer structure and has a resemblance to water's known ability to favor organic cycloaddition reactions. In an aqueous medium, a range of organic hosts selectively include only the nitrosocumene monomer 1a. Encapsulation in the octa acid duplex (OA2) selects two 1a monomers rather than a dimer structure. Octa acid encapsulation also results in more restricted intramolecular C-N rotations of the guest 1b.

A pilot study using geospatial analysis to identify hot-spot of populations utilizing services at university based counseling centers.

Objective: Our pilot study tests whether university counseling centers (UCC) can apply the concept of cluster analysis, and geospatial analysis to identify clusters of "hot spots". Participants: Study participants were university students who received services from a large mid-western UCC between August 2015 and July 2016. The study was approved by the University's Institutional Review Board (IRB). Data collected include demographics, address, educational level and declared major. Methods: Data analysis, conducted using SYSTAT 13.1, IBM SPSS Statistics, ArcGIS Desktop and 10.2, ArcOnline, Microsoft excel to clean and analyze demographic data. Analysis included optimized cluster analysis with a p-value < 0.05 as statistically significant. Results: 927 participants, average age was 21.6. We identified "hotspots" using cluster analysis based on age, address, and country of origin. Conclusions: Our study shows that UCCs can apply cluster analysis, and geospatial analysis to identify clusters of "hot spots" to target risk populations.

Expression of cancer stem cell markers in tall cell variant papillary thyroid cancer identifies a molecular profile predictive of recurrence in classic papillary thyroid cancer.

BACKGROUND: Tall cell variant of papillary thyroid carcinoma is an aggressive subtype of papillary thyroid carcinoma. We examined expression of cancer stem cell markers in tall cell variant compared with other well-differentiated thyroid cancers. METHODS: Expression of cancer stem cell markers was examined in 572 thyroid tumors from The Cancer Genome Atlas Thyroid Cancer database and tall cell variant and papillary thyroid carcinoma tumors by immunohistochemistry. RESULTS: Expression of the PROM1 gene, encoding the cancer stem cell marker CD133, was elevated in tall cell variant compared to classic papillary thyroid carcinoma in a large cohort of unmatched samples from The Cancer Genome Atlas Thyroid Cancer database (P < .001). By immunohistochemistry in age and stage matched samples, CD133 protein was confirmed to be significantly increased in tall cell variant versus classic papillary thyroid carcinoma (P = .006). Analyzing all thyroid cancers, high PROM1 expression was associated with worse disease-specific survival. Optimal cutoffs were determined to define a tall cell variant-like cancer stem cell signature characterized by high PROM1, high ALDH1A3, and low CD24 expression. Classic papillary thyroid carcinoma with a tall cell variant-like gene signature had worse recurrence disease-free survival compared to classic papillary thyroid carcinoma with a non-tall cell variant signature (P = .02). CONCLUSION: Tall cell variant of papillary thyroid carcinoma has increased expression of cancer stem cell markers compared to classic papillary thyroid carcinoma. The tall cell variant-like cancer stem cell gene signature identified a molecular subtype of classic papillary thyroid carcinoma that has a worse recurrence-free survival.

Pathways from child maltreatment to proactive and reactive aggression: The role of posttraumatic stress symptom clusters.

OBJECTIVE: Childhood aggression is related to a myriad of negative concurrent and long-term outcomes. To mitigate the risks associated with childhood aggression, it is important to understand risk factors that might predispose 1 to aggressive behaviors. One risk factor commonly associated with aggression is the experience of child maltreatment. A common outcome associated with child maltreatment is the development of posttraumatic stress symptoms (PTSS). Several prevailing theoretical models of both posttraumatic stress and aggression indicate that these constructs have similar underlying cognitive, behavioral, and emotional mechanisms. Therefore, the present study examined the relations between and among child maltreatment, PTSS clusters, and proactive and reactive aggression in children. METHOD: Children between the ages of 6 and 14 who were enrolled in a residential treatment program completed self-report measures to evaluate variables of interest. These variables were included as multiple outcomes in a path analysis model in which individual PTSS clusters were examined as potential multiple mediators of the relations between child maltreatment and proactive and reactive aggression. RESULTS: Direct effects of child maltreatment and PTSS clusters on aggression were observed. Significant indirect effects of the intrusion PTSS cluster on the relation between child maltreatment and reactive aggression was found. CONCLUSIONS: Findings suggest that symptoms associated with these specific PTSS clusters might help explain the relation between child maltreatment and reactive aggression and therefore present important implications for clinical practice and future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Ending Restraint of Incarcerated Individuals Giving Birth.

Advocates have long suggested making shackling incarcerated people during childbirth illegal. Yet exceptions would likely still allow prison personnel to implement restraint and leave clinicians no course for freeing a patient. This article argues that clinicians' assessments of laboring individuals' clinical needs must be prioritized, ethically and legally. This article also explains that, without strong policies in place, some clinicians will not feel empowered to demand that a patient be freed during labor. Beyond prohibiting restraint of laboring individuals, health care organizations must support clinicians seeking to execute their ethical duties to care well and justly for patients. Toward this end, this article proposes a model policy.

Treatment Practices and Outcomes in Continuous Spike and Wave during Slow Wave Sleep: A Multicenter Collaboration.

OBJECTIVES: To determine how continuous spike and wave during slow wave sleep (CSWS) is currently managed and to compare the effectiveness of current treatment strategies using a database from 11 pediatric epilepsy centers in the US. STUDY DESIGN: This retrospective study gathered information on baseline clinical characteristics, CSWS etiology, and treatment(s) in consecutive patients seen between 2014 and 2016 at 11 epilepsy referral centers. Treatments were categorized as benzodiazepines, steroids, other antiseizure medications (ASMs), or other therapies. Two measures of treatment response (clinical improvement as noted by the treating physician; and electroencephalography improvement) were compared across therapies, controlling for baseline variables. RESULTS: Eighty-one children underwent 153 treatment trials during the study period (68 trials of benzodiazepines, 25 of steroids, 45 of ASMs, 14 of other therapies). Children most frequently received benzodiazepines (62%) or ASMs (27%) as first line therapy. Treatment choice did not differ based on baseline clinical variables, nor did these variables correlate with outcome. After adjusting for baseline variables, children had a greater odds of clinical improvement with benzodiazepines (OR 3.32, 95%CI 1.57-7.04, P = .002) or steroids (OR 4.04, 95%CI 1.41-11.59, P = .01) than with ASMs and a greater odds of electroencephalography improvement after steroids (OR 3.36, 95% CI 1.09-10.33, P = .03) than after ASMs. CONCLUSIONS: Benzodiazepines and ASMs are the most frequent initial therapy prescribed for CSWS in the US. Our data suggests that ASMs are inferior to benzodiazepines and steroids and support earlier use of these therapies. Multicenter prospective studies that rigorously assess treatment protocols and outcomes are needed.

Systematic Review and Meta-Analysis of the Clinical Utility of the ADOS-2 and the ADI-R in Diagnosing Autism Spectrum Disorders in Children.

The Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) and the Autism Diagnostic Interview, Revised (ADI-R) have high accuracy as diagnostic instruments in research settings, while evidence of accuracy in clinical settings is less robust. This meta-analysis focused on efficacy of these measures in research versus clinical settings. Articles (n = 22) were analyzed using a hierarchical summary receiver operating characteristics (HSROC) model. ADOS-2 performance was stronger than the ADI-R. ADOS-2 sensitivity and specificity ranged from .89-.92 and .81-.85, respectively. ADOS-2 accuracy in research compared with clinical settings was mixed. ADI-R sensitivity and specificity were .75 and .82, respectively, with higher specificity in research samples (Research = .85, Clinical = .72). A small number of clinical studies were identified, indicating ongoing need for investigation outside research settings.

Testing a Tailored Social-Ecological Model for Autism Spectrum Disorders.

OBJECTIVE: To propose a tailored social ecological model for Autism Spectrum Disorders and explore relationships between variables in a large nationally-representative dataset. METHODS: A tailored social-ecological model was developed and examined across variables in the 2016/2017 National Survey of Children's Health. A series of iterative multivariable logistic regressions were performed including individual, family, and community/neighborhood variables. A multivariable logistic regression using state-level fixed effects was performed to understand dynamics related to macro-level policies. RESULTS: In the full model, gender, disability severity, certain types of insurance coverage and household income were significantly related to ASD diagnosis. Females had lower odds of a diagnosis compared to males (aOR: 0.27; CI:0.18-0.41). Children with at least one other moderate/severe disability had odds 7.61 higher (CI:5.36-10.82) of a diagnosis than children without moderate/severe disabilities. Children with public insurance only (aOR:1.66; CI:1.14-2.41) or both private and public insurance coverage (aOR: 2.62; CI:1.6-4.16) had higher odds of a diagnosis compared to children with private insurance only. For those who reported it was "somewhat" or "very often" hard to cover basics with their income, odds of a diagnosis were higher compared to those who reported it was "never" or "hardly ever" hard to cover basics (aOR: 1.676; CI:0.21-2.56). CONCLUSIONS FOR PRACTICE: Patterns of ASD diagnosis are related to individual and family characteristics. There is some evidence that a child's environment has some relationship to reported ASD diagnosis. Professionals should be aware of an individual's environmental factors or context when assessing for ASD.

Diagnosing and managing childhood absence epilepsy by telemedicine.

The diagnosis of childhood absence epilepsy (CAE) is typically based on history and description of spells, supported by an office-based positive hyperventilation test and confirmed by routine electroencephalography (EEG). In the current coronavirus disease 2019 (COVID-19) pandemic, many pediatric neurologists have switched to telemedicine visits for nonemergent outpatient evaluations. We present a series of children diagnosed as having CAE on the basis of a positive hyperventilation test performed during remote televisits. Several of these children were begun on treatment for CAE prior to obtaining an EEG, with significant seizure reduction. Our series documents the feasibility of CAE diagnosis and management by telemedicine.

Comorbid Internalizing and Externalizing Symptoms Among Children with ADHD: The Influence of Parental Distress, Parenting Practices, and Child Routines.

Emotional/behavioral concerns are common among children with ADHD. Familial factors (e.g., parental adjustment, parenting behaviors) are linked to the presence of comorbid internalizing/externalizing symptoms among children with ADHD. The purpose of the present study was to evaluate a model that includes multiple familial variables and their direct and indirect effects on child emotional and behavioral problems among children with ADHD. Participants included parents of children (6-12 years of age; M = 8.87, SD = 1.92) with a diagnosis of ADHD (N = 300). Participants completed measures of child emotional/behavioral concerns, parental distress, routines, and parenting behaviors. Path analyses revealed direct effects for parental distress, parent behavior and routines on child adjustment, after controlling for the other variables. A significant indirect relation between parental distress, routines, and externalizing behavior was observed. These findings highlight one specific path through which parental distress appears to influence specific behavioral concerns that are commonly observed in children with ADHD.