ADOS Scores Research Articles

Contribution of Anemia to Multidimensional Indices for Predicting Mortality in Hospitalized Patients With Chronic Obstructive Pulmonary Disease (COPD).

Severe exacerbations are a significant predictor of poor prognosis and mortality in patients with chronic obstructive pulmonary disease (COPD). Multidimensional indices, such as the BODE (BMI, airflow obstruction, dyspnea, and exercise capacity) and ADO indices (age, dyspnea severity, and airflow obstruction), outperform single-variable assessments in predicting survival. However, anemia, a strong predictor of mortality in both the general population and COPD patients, has not been included in the prediction indices. This study aimed to evaluate whether including anemia as a variable enhances the predictive accuracy of these indices for both short-term and long-term mortality in COPD patients. Data from patients who were consecutively admitted for acute exacerbation of COPD were recorded with a minimum follow-up of three years. Patients were divided into two groups: anemic (Hb <12 g/dL in women and Hb <13 g/dL in men) or non-anemic. Modified versions of the BODEx (BMI, airflow obstruction, dyspnea, and exacerbation) and ADO indices that included anemia, termed BODEx-A3 and ADO-A3, were created by adding three points to the original values. A total of 141 patients were included. Twenty-one (15%) died during the first year after admission, and 48 (34%) died during the three-year follow-up period. The area under the receiver operating characteristic curve (AUC) for predicting one-year mortality was slightly higher with the BODEx-A3 compared to the BODEx (0.83 vs. 0.78) and with the ADO-A3 compared to the ADO (0.81 vs. 0.78). For three-year mortality, the predictive power of the BODEx-A3 (AUC 0.77 vs. 0.67 for BODEx, p<0.001) and ADO-A3 indices (AUC 0.82 vs. 0.77 for ADO, p=0.038) was significantly greater compared to their original versions. We have defined novel multidimensional indices (BODEx-A3 and ADO-A3) for predicting short- and long-term mortality in patients hospitalized with COPD exacerbation. These indices were derived by adding three points to the standard BODEx and ADO scores in anemic patients. Our findings demonstrate that incorporating anemia into the best existing COPD mortality predictor indices significantly improves their predictive capacity.

Relationships between tryptophan-related gut metabolites, brain activity, and autism symptomatology.

Gut microbial metabolites have been theorized to play a causative role in the pathophysiology of autism spectrum disorder (ASD). This hypothesis is based on results from mechanistic preclinical studies and several correlational studies showing differences in gut microbial composition between ASD subjects and neurotypical (NT) controls. However, alterations in how the human brain interacts with the gut microbiome in ASD have not been examined. In this cross-sectional, case-control observational study, fecal metabolomics, task-based functional magnetic resonance imaging (fMRI), and behavioral assessments were obtained from 43 ASD and 41 NT children aged 8-17. The fMRI tasks were based on socio-emotional and sensory paradigms that commonly show strong evoked brain differences in ASD participants. General linear models and mediational modeling were applied to examine the links between tryptophan metabolism and evoked brain activity and behavior. Results indicated that fecal levels of specific tryptophan-related metabolites were associated with: 1) brain activity atypicalities in regions previously implicated in ASD (i.e., insula and cingulate); and 2) ASD severity and symptomatology (i.e., ADOS scores, disgust propensity, and sensory sensitivities). Importantly, activity in the mid-insula and mid-cingulate significantly mediated relationships between the microbial tryptophan metabolites, indolelactate and tryptophan betaine, and ASD severity and disgust sensitivity. To our knowledge, this is the first study to elucidate how interactions between gut metabolites and brain activity may impact autism symptomatology, particularly in functional brain pathways associated with vagal and interoceptive/emotion processing.

Autism Symptom Presentation and Hierarchical Models of Intelligence.

There is a substantial history studying the relationship between general intelligence and the core symptoms of autism. However, a gap in knowledge is how dimensional autism symptomatology associates with different components of clinically-relevant hierarchical models of intelligence. We examined correlations between autism diagnostic symptom magnitude (Autism Diagnostic Observational Schedule; ADOS) and a hierarchical statistical model of intelligence. One autistic cohort was tested on the fourth edition of Wechsler Intelligence Scale for Children (WISC-IV; N = 131), and another on the fifth edition (WISC-V; N = 83). We anticipated a convergent pattern of results between cohorts. On WISC-IV, ADOS scores were correlated significantly with g and three out of four intermediate factor scores, which was a broader pattern of correlations than anticipated from the literature. In the WISC-V cohort, only one intermediate factor correlated significantly with the ADOS; correlations with g and the other intermediate factors were less statistically certain. ADOS-factor correlations were larger in the WISC-IV than WISC-V cohort; this difference was significant at the 90% level. WISC-IV shows dimensional relationships with ADOS at multiple points in the hierarchical model of intelligence. Moreover, the current results provide evidence that relationship between core autism symptomatology and the construct of general intelligence may depend on how intelligence is measured. Known cohort effects in the relationship between categorical autism diagnosis and general intelligence have previously been attributed to changes in autism diagnostic practices. To our knowledge, this is the first evidence that differing versions of IQ tests may be implicated.

Clinical correlates of diagnostic certainty in children and youths with Autistic Disorder

BackgroundClinicians diagnosing autism rely on diagnostic criteria and instruments in combination with an implicit knowledge based on clinical expertise of the specific signs and presentations associated with the condition. This implicit knowledge influences how diagnostic criteria are interpreted, but it cannot be directly observed. Instead, insight into clinicians’ understanding of autism can be gained by investigating their diagnostic certainty. Modest correlations between the certainty of an autism diagnosis and symptom load have been previously reported. Here, we investigated the associations of diagnostic certainty with specific items of the ADOS as well as other clinical features including head circumference.MethodsPhenotypic data from the Simons Simplex Collection was used to investigate clinical correlates of diagnostic certainty in individuals diagnosed with Autistic Disorder (n = 1511, age 4 to 18 years). Participants were stratified by the ADOS module used to evaluate them. We investigated how diagnostic certainty was associated with total ADOS scores, age, and ADOS module. We calculated the odds-ratios of being diagnosed with the highest possible certainty given the presence or absence of different signs during the ADOS evaluation. Associations between diagnostic certainty and other cognitive and clinical variables were also assessed.ResultsIn each ADOS module, some items showed a larger association with diagnostic certainty than others. Head circumference was significantly higher for individuals with the highest certainty rating across all three ADOS modules. In turn, head circumference was positively correlated with some of the ADOS items that were associated with diagnostic certainty, and was negatively correlated with verbal/nonverbal IQ ratio among those assessed with ADOS module 2.LimitationsThe investigated cohort was heterogeneous, e.g. in terms of age, IQ, language level, and total ADOS score, which could impede the identification of associations that only exist in a subgroup of the population. The variability of the certainty ratings in the sample was low, limiting the power to identify potential associations with other variables. Additionally, the scoring of diagnostic certainty may vary between clinicians.ConclusionSome ADOS items may better capture the signs that are most associated with clinicians’ implicit knowledge of Autistic Disorder. If replicated in future studies, new diagnostic instruments with differentiated weighting of signs may be needed to better reflect this, possibly resulting in better specificity in standardized assessments.

Examining Diagnostic Trends and Gender Differences in the ADOS-II.

Approximately 3-4 boys for every girl meet the clinical criteria for autism in studies of community diagnostic patterns and studies of autism using samples of convenience. However, girls with autism have been hypothesized to be underdiagnosed, possibly because they may present with differing symptom profiles as compared to boys. This secondary data analysis used the National Database of Autism Research (NDAR) to examine how gender and symptom profiles are associated with one another in a gold standard assessment of autism symptoms, the Autism Diagnostic Observation Schedule II (ADOS-II; Lord, C., Luyster, R., Guthrie, W., & Pickles A. (2012a). Patterns of developmental trajectories in toddlers with autism spectrum disorder. Journal of Consulting and Clinical Psychology, 80(3):477-489. https://doi.org/10.1037/a0027214 . Epub 2012 Apr 16. PMID: 22506796, PMCID: PMC3365612). ADOS-II scores from 6183 children ages 6-14 years from 78 different studies in the NDAR indicated that gender was a significant predictor of total algorithm, restrictive and repetitive behavioral, and social communicative difficulties composite severity scores. These findings suggest that gender differences in ADOS scores are common in many samples and may reflect on current diagnostic practices.

A Machine Learning Approach to the Diagnosis of Autism Spectrum Disorder and Multi-Systemic Developmental Disorder Based on Retrospective Data and ADOS-2 Score.

Early and accurate diagnosis of autism spectrum disorders (ASD) and tailored therapeutic interventions can improve prognosis. ADOS-2 is a standardized test for ASD diagnosis. However, owing to ASD heterogeneity, the presence of false positives remains a challenge for clinicians. In this study, retrospective data from patients with ASD and multi-systemic developmental disorder (MSDD), a term used to describe children under the age of 3 with impaired communication but with strong emotional attachments, were tested by machine learning (ML) models to assess the best predictors of disease development as well as the items that best describe these two autism spectrum disorder presentations. Maternal and infant data as well as ADOS-2 score were included in different ML testing models. Depending on the outcome to be estimated, a best-performing model was selected. RIDGE regression model showed that the best predictors for ADOS social affect score were gut disturbances, EEG retrievals, and sleep problems. Linear Regression Model showed that term pregnancy, psychomotor development status, and gut disturbances were predicting at best for the ADOS Repetitive and Restricted Behavior score. The LASSO regression model showed that EEG retrievals, sleep disturbances, age at diagnosis, term pregnancy, weight at birth, gut disturbances, and neurological findings were the best predictors for the overall ADOS score. The CART classification and regression model showed that age at diagnosis and weight at birth best discriminate between ASD and MSDD.

Comparison of an online adaptation of the Autism Diagnostic Observation Schedule-2 with its in-person version in an adult autism diagnostic service.

Restrictions on in-person assessments during the COVID-19 pandemic were a challenge for an adult autism diagnostic service receiving over 600 referrals annually. The service sought to adapt the Autism Diagnostic Observation Schedule (ADOS-2) for online administration. To investigate whether an online adaptation of the ADOS-2 performed comparably to the in-person ADOS-2. To obtain qualitative feedback from patients and clinicians regarding experiences of the online alternative. Online ADOS-2 assessments were completed for 163 referred individuals. A matched-comparison group comprised 198 individuals seen for an in-person ADOS-2 assessment prior to COVID-19 restrictions. A two-way analysis of variance (ANOVA) was run to explore any effect of assessment type (online or in-person ADOS-2) and gender on total ADOS score. Qualitative feedback was collected from 46 patients and 8 clinicians involved in diagnostic decision-making after the online ADOS-2 assessment. A two-way ANOVA found no significant effect of assessment type or gender and no assessment type × gender interaction effect on total ADOS score. Qualitative feedback suggested that only 27% of patients would have preferred an in-person assessment. Nearly all clinicians reported gains from offering an online alternative. This is the first study to examine an online adaptation of ADOS-2 within an adult autism diagnostic service. It performed comparably to the in-person ADOS-2, making it a viable alternative when in-person assessments are not possible. As this clinic group has high rates of comorbid mental health difficulties, we encourage further work to determine whether online assessment approaches generalise to other services to increase options for patients and efficiencies for service delivery.

Young children with autism show atypical prefrontal cortical responses to humanoid robots: An fNIRS study

BackgroundPrevious behavioral studies have found that children with autism spectrum disorder (ASD) show greater interest in humanoid robots than in humans. However, the neural mechanism underlying this is not clear. This study compared brain activation patterns between children with ASD and neurotypical children while they watched videos with robots and humans. MethodWe recruited 45 children with ASD and 53 neurotypical children aged 4–6 years and recorded their neural activity in the dorsolateral prefrontal cortex (DLPFC) using a functional near-infrared spectroscopy (fNIRS) device when the two groups interacted with a robot or a human in a video. ResultsFirst, neural activity in the right DLPFC in children with ASD was significantly lower in the robot condition than in the human condition. Neural activity in the right DLPFC in children with ASD was also significantly lower than that of neurotypical children in the robot condition. Second, the neural activity in the left DLPFC between the human and robot conditions was negatively correlated in children with ASD, while it was positively correlated in neurotypical children. Moreover, neural activity in the left DLPFC in children with ASD was significantly correlated with the ADOS scores in both conditions. ConclusionsWhile neurotypical children showed comparable neural activity to humanoid robots and human beings, the children with ASD showed significantly different neural activity under those two conditions. Children with ASD may need more selective attention resources for human interaction than for robot interaction. It is also much more difficult for children with ASD to neglect the attraction of robots. Neural activity of the left DLPFC of children with ASD is correlated with their symptoms, which maybe a possible indicator for early diagnosis. Neural activity of the right DLPFC guided their atypical reactions and engagements with robots. Our study contributes to the current understanding of the neural mechanisms responsible for the different behavioral reactions in children with ASD toward robots and humans.

Vitamin D Status in Children with Autism Spectrum Disorders: Determinants and Effects of the Response to Probiotic Supplementation.

A relationship between the presence of clinical symptoms and gastrointestinal (GI) disturbances associated with nutritional deficiencies, including vitamin D (25(OH)D) deficiency, has been observed in autism spectrum disorder (ASD). The aim was to evaluate 25(OH)D levels according to the annual rhythm cycle, gender, the severity of autism, nutritional or clinical status, inflammatory and metabolic biomarkers, GI symptoms, and the clinical response to probiotic/placebo supplementation in preschooler children with ASD. Eighty-one ASD preschoolers (67 males) were assessed with standardized tools for ASD severity (ADOS score) and GI symptoms (by GI-Index at six-items and at nine-items, the latter defined as the Total GI-Index). The 25(OH)D levels were compared among different ASD subgroups according to metabolic and inflammatory biomarkers (leptin, insulin, resistin, PAI-1, MCP-1, TNF-alfa, and IL-6), gender, and the presence or absence of: (i) GI symptoms, (ii) the response to probiotic supplementation (the improvement of GI symptomatology), (iii) the response to probiotic supplementation (improvement of ASD severity). Only 25% of the ASD children presented an adequate 25(OH)D status (≥30 ng/mL according to the Endocrine Society guidelines). All the 25(OH)D levels falling in the severe deficiency range (<10 ng/mL) were observed in the male subgroup. A significant inverse correlation between 25(OH)D and leptin was observed (R = −0.24, p = 0.037). An inverse correlation was found between 25(OH)D levels and the GI Index 6-Items and Total GI-Index (R = −0.25, p = 0.026; −0.27, = 0.009) and a direct relationship with the probiotic response (R = 0.4, p = 0.05). The monitoring of 25(OH)D levels and the co-administration of 25(OH)D and probiotic supplementation could be considered in ASD from early ages.

Autism spectrum disorder in preschool children in Sør-Trøndelag 2016-19.

Autism spectrum disorder (ASD) is an umbrella term covering a range of conditions characterised by challenges with social interaction, restricted interests and repetitive behaviours. The prevalence of ASD has increased significantly in recent years, and there is a clinical impression of a preponderance of cases among young children whose mothers were not born in Norway. The study included 142 children aged 2 to 6 years who were diagnosed with autism in the county of Sør-Trøndelag, Norway in the period 2016-2019. The following information was collected: age at onset of symptoms and diagnosis, primary diagnosis, ADOS-2 (Autism Diagnostic Observation Schedule) scores, whether the child was born in Norway and the mother's country of birth. Children of mothers born outside of Norway had a 7.7 times higher risk of being diagnosed with autism than children of Norwegian-born mothers, with an annual incidence of 0.74% and 0.10% respectively. These children were diagnosed earlier, at an average age (standard deviation) of 41.9 (11.8) and 51.8 (18.1) months respectively (95% CI 4.7 to 15.2); a p-value of <0.001 for the difference. They also had a higher ADOS score, with an average (standard deviation) of 19.0 (6.2) and 15.3 (7.1) respectively. The preponderance of autism diagnoses may be an indication that the mothers' country of origin has an impact on the development of the condition. This has implications for adaptions to the assessment and follow-up of this patient group.

Diagnostic stability in individuals with autism spectrum disorder: insights from a longitudinal follow‐up study

Background:This longitudinal study of autism symptom trajectories provides unique information that can characterize autism features and diagnostic patterns from childhood to adulthood.Methods:Participants (n = 155) were part of a longitudinal cohort referred for possible autism where in-person assessments were completed at ages 2, 3, 5, 9, 19, and 25. Assessors were blinded to previous diagnoses. Based on adult best estimate diagnoses, participants were categorized into one of the four groups: Retained ASD, Lost ASD, Never Had ASD, or Gained ASD Diagnosis. To examine developmental changes in autism symptoms, mixed models indicated the rate of change in ADOS CSS and ADI-R scores in each diagnostic group.Results:A subset of participants with VIQ> and <70 were assigned a diagnosis in adulthood that differed from diagnoses earlier in development. Across cognitive levels, the majority of novel diagnoses emerged in adulthood. For those with VIQ > 70, improvements in ADOS CSS over time for the Lost Diagnosis group and worsening in CSS in the Gained Diagnosis group were gradual. Individuals with VIQ > 70 who lost a diagnosis even in adulthood could be distinguished on CSS and ADI-R scores by age 5 from those who retained their ASD diagnosis. Although most participants with VIQ < 70 saw decreases in autistic symptoms as a whole, changes in autism diagnoses were confounded by disentangling profound intellectual disability as a differential diagnosis or co-occurrence. Only the Never Had Diagnosis group revealed significant changes in ADOS scores over time, with autism symptoms increasing.Conclusions:Associated with gradual changes in core features of autism beginning in childhood, diagnoses of autism can shift across development.

CLEAR Autism Diagnostic Evaluation (CADE): Evaluation of Reliability and Validity.

Recent surveillance efforts indicate that 1 in 54 American children meet the criteria for Autism Spectrum Disorder (ASD), making it the fastest growing neurodevelopmental disorder in the U.S. Despite evidence that ASD can be reliably diagnosed as early as 24 months, the median age at ASD diagnosis in 2016 in the U.S. was 51 months. The CLEAR Autism Diagnostic Evaluation (CADE; Willard & Kroncke, 2019), was developed in response to the need to improve, shorten, and standardize the clinical ASD evaluation process. The CADE is a 33-item rating scale designed to be completed by caregivers and clinicians. The current study was conducted to examine the reliability and validity of the CADE using a sample of 191 individuals who received a private evaluation for ASD. Using the client’s evaluation records, clinicians completed the CADE items. The coefficient alpha was .94, which indicates that the items form a scale that has high internal consistency. The CADE total scores were highly correlated with ADOS scores, with r values ranging from .52—.86, and discriminated between those participants with a diagnosis of ASD and those without (p < .001). Receiver operator characteristic (ROC) curve analyses indicated excellent diagnostic accuracy of the CADE total score (ROC area under the curve = .998). Results suggest that the CADE can be used as an efficient and accurate means of evaluating ASD. Limitations and implications for use of the CADE are discussed.

Dissecting the heterogeneous subcortical brain volume of autism spectrum disorder using community detection.

Structural brain alterations in autism spectrum disorder (ASD) are heterogeneous, with limited effect sizes overall. In this study, we aimed to identify subgroups in ASD, based on neuroanatomical profiles; we hypothesized that the effect sizes for case/control differences would be increased in the newly defined subgroups. Analyzing a large data set from the ENIGMA‐ASD working group (n = 2661), we applied exploratory factor analysis (EFA) to seven subcortical volumes of individuals with and without ASD to uncover the underlying organization of subcortical structures. Based on earlier findings and data availability, we focused on three age groups: boys (<=14 years), male adolescents (15–22 years), and adult men (> = 22 years). The resulting factor scores were used in a community detection (CD) analysis to cluster participants into subgroups. Three factors were found in each subsample; the factor structure in adult men differed from that in boys and male adolescents. From these factors, CD uncovered four distinct communities in boys and three communities in adolescents and adult men, irrespective of ASD diagnosis. The effect sizes for case/control comparisons were more pronounced than in the combined sample, for some communities. A significant group difference in ADOS scores between communities was observed in boys and male adolescents with ASD. We succeeded in stratifying participants into more homogeneous subgroups based on subcortical brain volumes. This stratification enhanced our ability to observe case/control differences in subcortical brain volumes in ASD, and may help to explain the heterogeneity of previous findings in ASD.Lay summary Structural brain alterations in ASD are heterogeneous, with overall limited effect sizes. Here we aimed to identify subgroups in ASD based on neuroimaging measures. We tested whether the effect sizes for case/control differences would be increased in the newly defined subgroups.Based on neuroanatomical profiles, we succeeded in stratifying our participants into more homogeneous subgroups. The effect sizes of case/control differences were more pronounced in some subgroups than those in the whole sample.

Microbiome-Specific Statistical Modeling Identifies Interplay Between Gastrointestinal Microbiome and Neurobehavioral Outcomes in Patients With Autism: A Case Control Study.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with unclear mechanisms of pathogenesis. Gastrointestinal microbiome alterations were found to correlate with ASD core symptoms, but its specific role in ASD pathogenesis has not been determined. In this study, we used a case-control strategy that simultaneously compared the ASD gastrointestinal microbiome with that from age-sex matched controls and first-degree relative controls, using a statistical framework accounting for confounders such as age. Enterobacteriaceae (including Escherichia/Shigella) and Phyllobacterium were significantly enriched in the ASD group, with their relative abundances all following a pattern of ASD > first degree relative control > healthy control, consistent with our hypothesis of living environment and shared microbial and immunological exposures as key drivers of ASD gastrointestinal microbiome dysbiosis. Using multivariable omnibus testing, we identified clinical factors including ADOS scores, dietary habits, and gastrointestinal symptoms that covary with overall microbiome structure within the ASD cohort. A microbiome-specific multivariate modeling approach (MaAsLin2) demonstrated microbial taxa, such as Lachnoclostridium and Tyzzerella, are significantly associated with ASD core symptoms measured by ADOS. Finally, we identified alterations in predicted biological functions, including tryptophan and tyrosine biosynthesis/metabolism potentially relevant to the pathophysiology of the gut-brain-axis. Overall, our results identified gastrointestinal microbiome signature changes in patients with ASD, highlighted associations between gastrointestinal microbiome and clinical characteristics related to the gut-brain axis and identified contributors to the heterogeneity of gastrointestinal microbiome within the ASD population.

Screen Time and Autism: Current Situation and Risk Factors for Screen Time Among Pre-school Children With ASD.

Objective: To investigate the current status of screen time in children with ASD, its correlation with autistic symptoms and developmental quotient (DQ), and the factors affecting screen time.Method: One hundred ninety-three Chinese children with ASD were recruited. We collected the demographic and screen time data using a questionnaire. The ASD core symptoms and developmental quotient (DQ) were measured by the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Autism Diagnostic Observation Schedule-Second Edition (ADOS-2), Griffiths Development Scales-Chinese Language Edition (GDS-C), and Chinese Children's Parent-Child Relationship Questionnaire (CPCIS). Then, we analyzed the correlations between the screen time of children with ASD and the ABC, CARS, ADOS, GDS-C DQs, and CPCIS scores. Linear regression was used to analyze the risk factors that affect screen time.Results: The children's average daily screen time was 2.64 ± 2.24 h. Forty eight percent children were exposed to two or more types of electronic devices. Their favorite activity of screen time was watching cartoons. Only 34% children spent screen time accompanied by parents and with communication. 50.26% children had no screen time before sleeping. The screen time of children with ASD had a negative correlation with the GDS-C CQ (r = −0.234, P = 0.001) and the CPCIS score (r = −0.180, P = 0.012) and a positive correlation with the CARS score (r = 0.192, P = 0.009). A low father's education level (P = 0.010), less restriction of the child's screen time by the guardian (P = 0.001), greater caregiver screen time (P < 0.001), the use of the screen as a tool for child rearing (P = 0.001), and the child's ownership of independent electronic equipment (P = 0.027) are risk factors for long screen time in children with ASD.Conclusion: The screen time of children with ASD in China is higher than the recommended standard, and the current situation is serious. The screen time of ASD children is related to their autism symptoms, DQ and parent-child interaction. Low paternal education levels, less restriction of children's screen time by guardians, greater guardian screen time, the use of screens in child rearing, and children's ownership of independent electronic equipment can lead to an increase in children's screen time. These findings may have implications for family intervention strategies.

Long Term Mortality in Hospitalized Chronic Obstructive Pulmonary Disease Exacerbation: A Comparison of Multiple Indices

The aim of this study is to identify the factors affecting mortality in patients with chronic obstructive pulmonary disease (COPD) hospitalized with exacerbation. A COPD cohort study was designed. Demographic data, the reason of mortality, Charlson co-morbidity index (CCI), COPD comorbidity index (COTE), age, dyspnea, airway obstruction (ADO) index, modified ADO index and dyspnea, airway obstruction, smoking, exacerbation (DOSE) index, and their relationship with mortality were investigated. One hundred and forty COPD patients hospitalized with exacerbation were included in the study. Eighty-seven (62.15%) of the patients were alive and 53 (37.85%) of them were deceased. The number of patients with CCI ≥ 7 was none in living patients and 11 (20.8%) in the deceased group (p<0.001). The percentage of treatment compliant patients during stable conditions was lower in the deceased group (p<0.001). ADO and COTE indices were significantly higher in the deceased group. There was no difference in modified ADO and DOSE scores between the groups. Multivariate analysis showed that lung cancer, CCI 7, hypoxemia (PaO2 <60 mmHg), and longer admission to the intensive care unit were independently associated with 3.4, 4.4, 2.1, and 3.0-fold mortality, respectively (p <0.05). Additionally, COTE ≥ 4 and noncompliance to regular COPD treatment were found to be associated with shorter survival in Kaplan Meier analysis (p<0.05). In conclusion, comorbidities and most notably lung cancer was associated with mortality in COPD. Also, high CCI and COTE index were risk factors for increased mortality.

Evaluation of Zn, Cu, and Se Levels in the North American Autism Spectrum Disorder Population

Metal ion dyshomeostasis and disparate levels of biometals like zinc (Zn), copper (Cu), and selenium (Se) have been implicated as a potential causative factor for Autism Spectrum Disorder (ASD). In this study, we have enrolled 129 children (aged 2–4 years) in North America, of which 64 children had a diagnosis of ASD and 65 were controls. Hair, nail, and blood samples were collected and quantitatively analyzed for Zn, Cu and Se using inductively coupled plasma mass spectrometry (ICP-MS). Of the analyzed biometals, serum Se (116.83 ± 14.84 ng/mL) was found to be significantly lower in male ASD cases compared to male healthy controls (128.21 ± 9.11 ng/mL; p < 0.005). A similar trend was found for nail Se levels in ASD (1.01 ± 0.15 mcg/g) versus that of controls (1.11 ± 0.17 mcg/g) with a p-value of 0.0132 using a stratified Wilcoxon rank sum testing. The level of Se in ASD cohort was co-analyzed for psychometric correlation and found a negative correlation between total ADOS score and serum Se levels. However, we did not observe any significant difference in Zn, Cu, and Zn/Cu ratio in ASD cases versus controls in this cohort of North American children. Further studies are recommended to better understand the biology of the relationship between Se and ASD status.

A 16-year study of longitudinal volumetric brain development in males with autism

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with unknown brain etiology. Our knowledge to date about structural brain development across the lifespan in ASD comes mainly from cross-sectional studies, thereby limiting our understanding of true age effects within individuals with the disorder that can only be gained through longitudinal research. The present study describes FreeSurfer-derived volumetric findings from a longitudinal dataset consisting of 607 T1-weighted magnetic resonance imaging (MRI) scans collected from 105 male individuals with ASD (349 MRIs) and 125 typically developing male controls (258 MRIs). Participants were six to forty-five years of age at their first scan, and were scanned up to 5 times over a period of 16 years (average inter-scan interval of 3.7 years). Atypical age-related volumetric trajectories in ASD included enlarged gray matter volume in early childhood that approached levels of the control group by late childhood, an age-related increase in ventricle volume resulting in enlarged ventricles by early adulthood and reduced corpus callosum age-related volumetric increase resulting in smaller corpus callosum volume in adulthood. Larger corpus callosum volume was related to a lower (better) ADOS score at the most recent study visit for the participants with ASD. These longitudinal findings expand our knowledge of volumetric brain-based abnormalities in males with ASD, and highlight the need to continue to examine brain structure across the lifespan and well into adulthood.

Differences in cortical activation patterns during action observation, action execution, and interpersonal synchrony between children with or without autism spectrum disorder (ASD): An fNIRS pilot study.

Engaging in socially embedded actions such as imitation and interpersonal synchrony facilitates relationships with peers and caregivers. Imitation and interpersonal synchrony impairments of children with Autism Spectrum Disorder (ASD) might contribute to their difficulties in connecting and learning from others. Previous fMRI studies investigated cortical activation in children with ASD during finger/hand movement imitation; however, we do not know whether these findings generalize to naturalistic face-to-face imitation/interpersonal synchrony tasks. Using functional near infrared spectroscopy (fNIRS), the current study assessed the cortical activation of children with and without ASD during a face-to-face interpersonal synchrony task. Fourteen children with ASD and 17 typically developing (TD) children completed three conditions: a) Watch-observed an adult clean up blocks; b) Do-cleaned up the blocks on their own; and c) Together-synchronized their block clean up actions to that of an adult. Children with ASD showed lower spatial and temporal synchrony accuracies but intact motor accuracy during the Together/interpersonal synchrony condition. In terms of cortical activation, children with ASD had hypoactivation in the middle and inferior frontal gyri (MIFG) as well as middle and superior temporal gyri (MSTG) while showing hyperactivation in the inferior parietal cortices/lobule (IPL) compared to the TD children. During the Together condition, the TD children showed bilaterally symmetrical activation whereas children with ASD showed more left-lateralized activation over MIFG and right-lateralized activation over MSTG. Additionally, using ADOS scores, in children with ASD greater social affect impairment was associated with lower activation in the left MIFG and more repetitive behavior impairment was associated with greater activation over bilateral MSTG. In children with ASD better communication performance on the VABS was associated with greater MIFG and/or MSTG activation. We identified objective neural biomarkers that could be utilized as outcome predictors or treatment response indicators in future intervention studies.

Effects of Probiotic Supplementation on Gastrointestinal, Sensory and Core Symptoms in Autism Spectrum Disorders: A Randomized Controlled Trial

The microbiota-gut-brain axis has been recently recognized as a key modulator of neuropsychiatric health. In this framework, probiotics (recently named “psychobiotics”) may modulate brain activity and function, possibly improving the behavioral profiles of children with Autism Spectrum Disorder (ASD). We evaluated the effects of probiotics on autism in a double-blind randomized, placebo-controlled trial of 85 preschoolers with ASD (mean age, 4.2 years; 84% boys). Participants were randomly assigned to probiotics (De Simone Formulation) (n=42) or placebo (n=43) for six months. Sixty-three (74%) children completed the trial. No differences between groups were detected on the primary outcome measure, the Total Autism Diagnostic Observation Schedule - Calibrated Severity Score (ADOS-CSS). An exploratory secondary analysis on subgroups of children with or without Gastrointestinal Symptoms (GI group, n= 30; NGI group, n=55) revealed in the NGI group treated with probiotics a significant decline in ADOS scores as compared to that in the placebo group, with a mean reduction of 0.81 in Total ADOS CSS and of 1.14 in Social-Affect ADOS CSS over six months. In the GI group treated with probiotics we found greater improvements in some GI symptoms, adaptive functioning, and sensory profiles than in the GI group treated with placebo. These results suggest potentially positive effects of probiotics on core autism symptoms in a subset of ASD children independent of the specific intermediation of the probiotic effect on GI symptoms. Further studies are warranted to replicate and extend these promising findings on a wider population with subsets of ASD patients which share targets of intervention on the microbiota-gut-brain axis.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02708901.