Functional Outcomes of Children Identified Early in the Developmental Period as at Risk for ASD Utilizing the The Norwegian Mother, Father and Child Cohort Study (MoBa).

Early identification of autism spectrum disorder (ASD) is regarded as crucial for swift access to early intervention and, subsequently, better outcomes later in life. However, current instruments miss large proportions of children who later go on to be diagnosed with ASD, raising a question of what these instruments measure. The present study utilized data from the Norwegian Mother, Father, and Child Cohort Study and the Autism Birth Cohort study to explore the subsequent developmental and diagnostic characteristics of children raising developmental concern on the six-critical discriminative item criterion of the M-CHAT (DFA6) at 18 months of age (N = 834). The DFA6 identified 28.8% of children diagnosed with ASD (N = 163), but 4.4% with language disorder (N = 188) and 81.3% with intellectual disability (N = 32) without ASD. Scoring in the «at-risk¼ range was associated with lower IQ, impaired functional language, and greater severity of autism symptoms whether children had ASD or not.

A Review Update on Gender Dysphoria and ASD and Response to Corrections.

Here we address the earlier published review by Øien et al. (J Autism Dev Disord, https://doi.org/10.1007/s10803-018-3686-7 , 2018) and the subsequent comments by Zucker and VanderLaan (J Autism Dev Disord, https://doi.org/10.1007/s10803-018-3748-x , 2018). The current commentary is a response to the corrections put forth by the latter authors where aspects related to diagnostic criteria of Gender Dysphoria and corrections to the existence of a control group were noted. Additionally, to highlight that research on Gender Dysphoria and ASD is becoming a very fast and growing field we also present an update of the original review which show a 13% increase of empirical studies published only in the past few months.

Enhancing the understanding of clinically meaningful results: A clinical research perspective.

Published research often address aspects related to "statistical significance" but fail to address the clinical and practical importance and meaning of results. Our main objectives in this article are to investigate the merit of common measures of Effect Size in statistical research and to highlight the importance of the simple Relative Risk ratio. In this article we present data where we consider two widely utilized effect size measures (Cohen's d and Pearson's r) in relations to relative risk. We conclude that probability analyses of risk surpass the most commonly used statistical approach used in clinical trials today and should thus be the preferred compared to the misuse and misunderstanding of reporting for instance p-values alone.

Gender Dysphoria, Sexuality and Autism Spectrum Disorders: A Systematic Map Review.

In this systematic map review, we aimed (1) at identifying studies including the co-occurrence of autism spectrum disorders (ASD) and gender dysphoria (GD) between 1946 and 2018, and (2) to present the papers included in this systematic map review to provide authors in the field of GD, sexuality and ASD with an important database of studies focusing on this very complex topic. The field is of emerging interest, as observed by the large increase of studies over the past decades, especially since 2015. However, future challenges are to be addressed in future studies.

Clinical Features of Children With Autism Who Passed 18-Month Screening.

OBJECTIVES: We compared sex-stratified developmental and temperamental profiles at 18 months in children screening negative for autism spectrum disorder (ASD) on the Modified Checklist for Autism in Toddlers (M-CHAT) but later receiving diagnoses of ASD (false-negative group) versus those without later ASD diagnoses (true-negative group). METHODS: We included 68 197 screen-negative cases from the Norwegian Mother and Child Cohort Study (49.1% girls). Children were screened by using the 6 critical items of the M-CHAT at 18 months. Groups were compared on domains of the Ages and Stages Questionnaire and the Emotionality Activity Sociability Temperament Survey. RESULTS: Despite passing M-CHAT screening at 18 months, children in the false-negative group exhibited delays in social, communication, and motor skills compared with the true-negative group. Differences were more pronounced in girls. However, with regard to shyness, boys in the false-negative group were rated as more shy than their true-negative counterparts, but girls in the false-negative group were rated as less shy than their counterparts in the true-negative group. CONCLUSIONS: This is the first study to reveal that children who pass M-CHAT screening at 18 months and are later diagnosed with ASD exhibit delays in core social and communication areas as well as fine motor skills at 18 months. Differences appeared to be more pronounced in girls. With these findings, we underscore the need to enhance the understanding of early markers of ASD in boys and girls, as well as factors affecting parental report on early delays and abnormalities, to improve the sensitivity of screening instruments.

Assessing Binary Diagnoses of Bio-behavioral Disorders: The Clinical Relevance of Cohen's Kappa.

Cohen's (Educ Psychol Meth. 1960;23:37-40) kappa statistic has been criticized recently for providing low chance-corrected coefficients (<0.40) despite high levels of examiner agreement (e.g., ≥85%). The AC1 statistic (Series. 2002;2:1-9; BMC Med Res Methodol. 2013;13:61), the alpha statistic (J Clin Epidemiol. 1996;49:775-782), the B statistic (BMC Med Res Methodol. 2013;13:97), and the delta statistic (Commun Statist Theory Meth. 2008;37:760-772) were developed to "correct" this "problem." Each of these statistics produces inaccurate results because they either derive from levels of chance agreement that are incorrect (Gwet's AC1 statistic) or fail to correct for chance levels of agreement (the alpha, B, and delta approaches). Implications for diagnoses of psychiatric disorders are critically discussed. The importance of kappa is demonstrated in a number of clinical scenarios.

Sensory features as diagnostic criteria for autism: sensory features in autism.

In this study, we examined the frequency of sensory-related issues as reported by parents in a large sample of school-age adolescents and adults with autism/autism spectrum disorder (ASD) [1] as compared to a group of individuals receiving similar clinical evaluations for developmental/behavioral difficulties but whose final diagnoses were not on the autism spectrum. In no comparison were the features examined predictive of autism or autism spectrum in comparison to the non-ASD sample. Only failure to respond to noises had sensitivity above .75 in the comparison of the broader autism spectrum group, but specificity was poor. While sensory issues are relatively common in autism/ASD, they are also frequent in other disorders. These results question the rationale for including sensory items as a diagnostic criterion for autism.

Reliability of the ADI-R for the single case-part II: clinical versus statistical significance.

In an earlier investigation, the authors assessed the reliability of the ADI-R when multiple clinicians evaluated a single case, here a female 3 year old toddler suspected of having an autism spectrum disorder (Cicchetti et al. in J Autism Dev Disord 38:764-770, 2008). Applying the clinical criteria of Cicchetti and Sparrow (Am J Men Def 86:127-137, 1981); and those of Cicchetti et al. (Child Neuropsychol 126-137, 1995): 74 % of the ADI-R items showed 100 % agreement; 6 % showed excellent agreement; 7 % showed good agreement; 3 % manifested average agreement; and the remaining 10 % evidenced poor agreement. In this follow-up investigation, the authors described and applied a novel method for determining levels of statistical significance of the reliability coefficients obtained in the earlier investigation. It is based upon a modification of the Z test for comparing a given level of inter-examiner reliability with a lower limit value of 70 % (Dixon and Massey in Introduction to statistical analysis. McGraw-Hill, New York, 1957). Results indicated that every item producing a clinically acceptable level of inter-examiner reliability was also statistically significant. However, the reverse was not true, since a number of the items with statistically significant reliability levels did not reach levels of agreement that were clinically meaningful. This indicated that clinical significance was an accurate marker of statistical significance. The generalization of these findings to other areas of diagnostic interest and importance is also examined.

On scales of measurement in Autism Spectrum Disorders (ASD) and beyond: where Smitty went wrong.

The author examined critically three beliefs of S.S. Stevens pertaining to his quadripartite system of scales of measurement: (1) There are four scales of measurement in common usage (2) These scales and the scientific disciplines that use them can be incrementally graded for levels of reliability and validity or accuracy such that: Nominal scale variables produce the lowest levels of reliability and accuracy; with successively improving levels for Ordinal, Equal Interval, and Equal Ratio scales; and (3) The scale upon which a variable is measured determines the type of statistical test that one is permitted to apply. It was shown that each of the three beliefs is fundamentally flawed.

From Bayes through marginal utility to effect sizes: a guide to understanding the clinical and statistical significance of the results of autism research findings.

The objectives of this report are: (a) to trace the theoretical roots of the concept clinical significance that derives from Bayesian thinking, Marginal Utility/Diminishing Returns in Economics, and the "just noticeable difference", in Psychophysics. These concepts then translated into: Effect Size (ES), strength of agreement, clinical significance, and related concepts, and made possible the development of Power Analysis; (b) to differentiate clinical significance from statistical significance; and (c) to demonstrate the utility of measures of ES and related concepts for enhancing the meaning of Autism research findings. These objectives are accomplished by applying criteria for estimating clinical significance, and related concepts, to a number of areas of autism research.

The role of adaptive behavior in autism spectrum disorders: implications for functional outcome.

The relationship between adaptive functioning and autism symptomatology was examined in 1,089 verbal youths with ASD examining results on Vineland-II, IQ, and measures of ASD severity. Strong positive relationships were found between Vineland subscales and IQ. Vineland Composite was negatively associated with age. IQ accounted a significant amount of the variance in overall adaptive skills (55%) beyond age and ASD severity. Individuals with ASD demonstrated significant adaptive deficits and negligible associations were found between the level of autism symptomatology and adaptive behavior. The results indicate that IQ is a strong predictor of adaptive behavior, the gap between IQ and adaptive impairments decreases in lower functioning individuals with ASD, and older individuals have a greater gap between IQ and adaptive skills.

Manual and automated reticulocyte counts.

Manual reticulocyte counts were examined under light microscopy, using the property whereby supravital stain precipitates residual ribosomal RNA versus the automated flow methods, with the suggestion that in the latter there is greater precision and an ability to determine both mature and immature reticulocyte fractions. Three hundred and forty-one venous blood samples of patients were analyzed of whom 224 newborn and the rest adults; 51 males and 66 females, with ages between 0 and 89 years, as part of the laboratory routine for hematological examinations at the Clinical Laboratory of the Hospital Universitário do Oeste do Paraná. This work aimed to compare manual and automated methodologies for reticulocyte countings and evaluate random and systematic errors. The results obtained showed that the difference between the two methods was very small, with an estimated 0·4% systematic error and 3·9% random error. Thus, it has been confirmed that both methods, when well conducted, can reflect precisely the reticulocyte counts for adequate clinical use.

Comparison of short and long versions of the Prudhoe Cognitive Function Test and the K-BIT in participants with intellectual impairment.

The Prudhoe Cognitive Function Test (PCFT) directly measures the cognitive abilities of people with intellectual impairment. This study examined the relationship between this instrument and the Kaufman Brief Intelligence Test (K-BIT) and two shorter versions of the same scale. High correlations between the verbal and performance sections of the K-BIT and the Long PCFT were found with correlation coefficients of 0.85 and 0.78, respectively. Extremely high correlations between the Short versions of the PCFT and the Long version were obtained at 0.97 for Form A and 0.98 for Form B, illustrating that both Short forms and the Long form are essentially interchangeable. The PCFT is a reliable and robust schedule in the assessment of cognitive function in this population.

Group intervention to promote social skills in school-age children with pervasive developmental disorders: reconsidering efficacy.

A consistent result in the evaluation of group-delivered intervention to promote social reciprocity in children with PDDs is that outcome data are inconclusive. Lack of robust evidence of efficacy confounds understanding of these interventions and their value to the field. It is conceivable that the construct of impaired social reciprocity in PDD presents unique circumstances that require special consideration when evaluating the evidence base. Social reciprocity and impairment in social functioning are complex constructs, which require a multi-dimensional, multi-method approach to intervention and measurement of gains. The existing paradigm for evaluating the evidence base of intervention may need modification to permit a more intricate analysis of the extant research, and increase the sophistication of future research.

Evaluating the reliability of multiple assessments of PTSD symptomatology: multiple examiners, one patient.

The objective of this investigation was to assess the inter-examiner reliability of PTSD symptomatology by 12 clinical examiners who evaluated independently a single-case Vietnam-Era veteran, using videotaped clinician interviews with The Clinician Administered PTSD Scale-1 (CAPS-1). A second patient was utilized for cross-validation purposes. Data were analyzed using a specially designed Kappa statistic. In previous reliability assessments of the CAPS-1, a pair of examiners assessed multiple patients, and demonstrated evidence of high reliability and validity. As in previous reliability assessments, reliability was assessed both for frequency and intensity of PTSD symptomatology in both patients. Results indicated that the reliability levels of the CAPS-1 were consistently and almost exclusively in the excellent to perfect levels of inter-examiner agreement, as based upon both global assessments and on a symptom-by-symptom basis. The results of this investigation are interpreted in the broader framework of their applicability to assessing inter-examiner agreement in clinical trials or other large multi-site studies.

Analysis of manual reticulocyte counts in the clinical laboratories of Ponta-Grossa and Campos Gerais, PR, Brazil

Reticulocyte counts are widely used in laboratories to evaluate bone marrow erythropoietic activity and have great diagnostic and prognostic importance in the treatment of anemias. Reticulocytes are supravitally stained with new methylene blue or brilliant cresyl blue, which highlight the characteristic aspect of the reticulum visible by light microscopy. Known criteria were observed for good manual reticulocyte counting with special attention being paid to the preparation of reticulocyte slides, to counting fields without overlapping cells, and to the number of evaluated cells. The aim of this study was to evaluate the inter-observer variation and also to analyze the statistical error of manual reticulocyte counting. The Intraclass correlation coefficient (ICC) according to Bartko was used to evaluate the level of agreement among 12 laboratory technicians who evaluated the same 25 blood smears. The results of statistical analyses showed that the amount of random error, defined as (1-r2), varied from 4 percent to 60 percent among the technicians. Although imprecision occurred, the overall profiles were quite similar, and intraclass correlation coefficients indicated that the results obtained have clinical significance.

A contagem do reticulócitos é usada extensamente na rotina laboratorial para avaliar a atividade eritropoiética da medula óssea, e é de grande importância no diagnóstico e no prognóstico na terapia de anemias hemolíticas. São coradas com o azul de metileno novo e o azul cresil brilhante, o que conferem o aspecto característico de retículo quando observado ao microscópioótico. Critérios conhecidos foram observados para um bom desempenho da contagem manual de reticulócitos, principalmente, atenção especial nas películas do sangue durante a montagem das lâminas; contagem nos campos que não contém sobreposição celular; e também no número de células avaliadas. O objetivo deste estudo foi avaliar a variação interobservadores, analisar o erro estatístico da contagem manual dos reticulócitos, e demonstrar as limitações deste método. A análise de correlação intraclasses segundo Bartko [Psychol Rep 19:3,1966; 34:418,1974] foi usada para avaliar a concordância entre 12 observadores em um total de 25 lâminas do sangue, com contagens variadas de reticulócitos. Os resultados das análises estatísticas indicam que o erro casual, calculado como (1-r2) variou de 4 a 60 por cento entre os observadores. Embora ocorra imprecisão entre os observadores, o perfil geral entre eles é similar, e o coeficiente de correlação intraclasse indicou que os resultados obtidos são clinicamente úteis.

Interexaminer agreement of histopathologic features in pediatric brain tumors: a biostatistical perspective.

Pages 108-117 of the current issue of Pediatric and Developmental Pathology contain a landmark interobserver investigation of some of the vagaries and vicissitudes involved in the nosological assessment of 6 histological features of childhood brain tumors. Doctor Gilles and his clinical research colleagues are to be commended for their conceptualization, reliability research design, execution, and interpretation of their findings. The piece is also uncommonly sophisticated concerning matters biostatistical. As such, it stands as a model for future nosological studies in childhood brain pathology, and can be applied more generally as well. The purpose of this Context article is to present some additional conceptual and methodologic issues that are relevant to the future design of histopathological studies in particular and of biobehavioral and biomedical diagnostic studies in general. In order to accomplish this goal, I shall discuss interexaminer reliability issues from the following viewpoints: type of reliability assessment, scales of measurement, reliability statistics, diagnostic accuracy, and the need to always differentiate levels of statistical significance from those that are both statistically and clinically meaningful, as Gilles and colleagues have also successfully accomplished.