Eye-Tracking-Based Measurement of Social Visual Engagement Compared With Expert Clinical Diagnosis of Autism.

Importance: In the US, children with signs of autism often experience more than 1 year of delay before diagnosis and often experience longer delays if they are from racially, ethnically, or economically disadvantaged backgrounds. Most diagnoses are also received without use of standardized diagnostic instruments. To aid in early autism diagnosis, eye-tracking measurement of social visual engagement has shown potential as a performance-based biomarker. Objective: To evaluate the performance of eye-tracking measurement of social visual engagement (index test) relative to expert clinical diagnosis in young children referred to specialty autism clinics. Design, Setting, and Participants: In this study of 16- to 30-month-old children enrolled at 6 US specialty centers from April 2018 through May 2019, staff blind to clinical diagnoses used automated devices to measure eye-tracking-based social visual engagement. Expert clinical diagnoses were made using best practice standardized protocols by specialists blind to index test results. This study was completed in a 1-day protocol for each participant. Main Outcomes and Measures: Primary outcome measures were test sensitivity and specificity relative to expert clinical diagnosis. Secondary outcome measures were test correlations with expert clinical assessments of social disability, verbal ability, and nonverbal cognitive ability. Results: Eye-tracking measurement of social visual engagement was successful in 475 (95.2%) of the 499 enrolled children (mean [SD] age, 24.1 [4.4] months; 38 [8.0%] were Asian; 37 [7.8%], Black; 352 [74.1%], White; 44 [9.3%], other; and 68 [14.3%], Hispanic). By expert clinical diagnosis, 221 children (46.5%) had autism and 254 (53.5%) did not. In all children, measurement of social visual engagement had sensitivity of 71.0% (95% CI, 64.7% to 76.6%) and specificity of 80.7% (95% CI, 75.4% to 85.1%). In the subgroup of 335 children whose autism diagnosis was certain, sensitivity was 78.0% (95% CI, 70.7% to 83.9%) and specificity was 85.4% (95% CI, 79.5% to 89.8%). Eye-tracking test results correlated with expert clinical assessments of individual levels of social disability (r = -0.75 [95% CI, -0.79 to -0.71]), verbal ability (r = 0.65 [95% CI, 0.59 to 0.70]), and nonverbal cognitive ability (r = 0.65 [95% CI, 0.59 to 0.70]). Conclusions and Relevance: In 16- to 30-month-old children referred to specialty clinics, eye-tracking-based measurement of social visual engagement was predictive of autism diagnoses by clinical experts. Further evaluation of this test's role in early diagnosis and assessment of autism in routine specialty clinic practice is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03469986.

Expert Clinician Certainty in Diagnosing Autism Spectrum Disorder in 16-30-Month-Olds: A Multi-site Trial Secondary Analysis.

Differential diagnosis of young children with suspected autism spectrum disorder (ASD) is challenging, and clinician uncertainty about a child's diagnosis may contribute to misdiagnosis and subsequent delays in access to early treatment. The current study was designed to replicate and expand a recent report in this Journal (McDonnell et al. in J Autism Dev Disord 49:1391-1401, https://doi.org/10.1080/15374416.2020.1823850 , 2019), in which only 60% of diagnoses were made with complete certainty by clinicians evaluating 478 toddlers and preschool children referred for possible ASD to specialized clinics. In this study, secondary analyses were performed on diagnostic, demographic and clinical data for 496 16-30-month-old children who were consecutive referrals to a 6-site clinical trial executed by specialized centers with experienced clinicians following best-practice procedures for the diagnosis of ASD. Overall, 70.2% of diagnoses were made with complete certainty. The most important factor associated with clinician uncertainty was mid-level autism-related symptomatology. Mid-level verbal age equivalents were also associated with clinician uncertainty, but measures of symptomatology were stronger predictors. None of the socio-demographic variables, including sex of the child, was significantly associated with clinician certainty. Close to one third of early diagnoses of ASD are made with a degree of uncertainty. The delineation of specific ranges on the ADOS-2 most likely to result in clinician uncertainty identified in this study may provide an opportunity to reduce random subjectivity in diagnostic decision-making via calibration of young-child diagnostic thresholds based on later-age longitudinal diagnostic outcome data, and via standardization of decision-making in regard to clinical scenarios frequently encountered by clinicians.

The PROXIMAL trial: proximal protection during saphenous vein graft intervention using the Proxis Embolic Protection System: a randomized, prospective, multicenter clinical trial.

OBJECTIVES: To determine if outcomes could be further improved, we investigated an embolic protection device placed proximal to the target lesion that could provide protection before lesion instrumentation, allow the use of conventional guidewires, and permit embolic protection in anatomy unfavorable for distal devices. BACKGROUND: Embolic complications during stenting of degenerated saphenous vein coronary bypass grafts are reduced, but not eliminated, by distal protection. METHODS: A total of 594 patients undergoing stenting of 639 saphenous vein grafts were prospectively randomized, using a noninferiority design, to compare 2 treatment strategies: control (distal protection whenever possible) or test (proximal protection when possible, distal when not). RESULTS: The primary composite end point of death, myocardial infarction, or target vessel revascularization at 30 days by intention to treat analysis occurred in 10.0% of control and 9.2% of test patients; difference = -0.8% (95% confidence interval [CI] -5.5% to 4.0%); p for noninferiority = 0.0061. In device specific analysis, this composite end point occurred in 11.7% of distal protection patients and 7.1% of proximal protection patients (difference = -4.6% [95% CI -9.6% to 0.3%]; p for superiority = 0.10, p for noninferiority = 0.001). Finally, in the subset of patients with lesions amenable to treatment with either proximal or distal protection devices (n = 410), the primary composite end point occurred in 12.2% of distal protection patients and 7.4% of proximal protection patients; difference = -4.7% (95% CI -10.4% to 1.0%), p for superiority = 0.14, p for noninferiority = 0.001. CONCLUSIONS: Using proximal embolic protection whenever possible during treatment of diseased saphenous vein grafts produced outcomes similar to those with distal embolic protection.