Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort.

PURPOSE: Genome sequencing (GS)-specific diagnostic rates in prospective tightly ascertained exome sequencing (ES)-negative intellectual disability (ID) cohorts have not been reported extensively. METHODS: ES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID. RESULTS: The ES diagnostic yield was 42 of 74 (57%). GS diagnoses were made in 9 of 32 (28%) ES-unresolved families. Repeated ES with a contemporary pipeline on the GS-diagnosed families identified 8 of 9 single-nucleotide variations/copy-number variations undetected in older ES, confirming a GS-unique diagnostic rate of 1 in 32 (3%). Episignatures contributed diagnostic information in 9% with GS corroboration in 1 of 32 (3%) and diagnostic clues in 2 of 32 (6%). A genetic etiology for ID was detected in 51 of 74 (69%) families. Twelve candidate disease genes were identified. Contemporary ES followed by GS cost US$4976 (95% CI: $3704; $6969) per diagnosis and first-line GS at a cost of $7062 (95% CI: $6210; $8475) per diagnosis. CONCLUSION: Performing GS only in ID trios would be cost equivalent to ES if GS were available at $2435, about a 60% reduction from current prices. This study demonstrates that first-line GS achieves higher diagnostic rate than contemporary ES but at a higher cost.

Psychometric Properties of the Dutch Contextual Assessment of Social Skills (CASS): An Independent Observational Outcome Measure of Social Skills in Autistic Adolescents.

The goal of this study was to translate and adapt the original 9-item of the Contextual Assessment of Social Skills (CASS) to a Dutch version and assess its psychometric qualities. Autistic adolescents aged 12 to 18 years (n = 99) took part in a randomized controlled trial. In this study, pre-intervention data were utilized. The original CASS was adapted to ensure cultural relevance and the content validity was assessed. Data was used to assess reliability and structural validity, using confirmatory factor analysis. 4-item were added to the CASS during the adaptation to better align with the objectives of the experimental intervention. The original 9-item had inter-item correlations between .01 and .70. The Cronbach's alpha for the original 4-item total score was moderate (α = .69), while for a 7-item total score, it was high (α = .86). This 7-item total score had a sufficient model fit (Comparative Fit Index = .90). This total score had a significant correlation with the Assertion subscale of the Social Skills Improvement System-Adolescent (SSIS-A) (r = 0.26, p < .01), and the Social Responsiveness Scale-2 (SRS-2) total score (r = - .21, p = .04) indicating sufficient convergent validity. The CASS total score was not correlated with the Repetitive and Restricted Behavior scale of the SRS-2 (r = - .08, p = .43), indicating sufficient divergent validity. The Dutch CASS can be considered a conceptually sound and reliable observational instrument for assessing social conversational skills in Dutch autistic youth. Further evaluation of its feasibility when implemented in practice, outside of clinical research, is needed.Trial registration: Dutch trail register NTR6255 (NL6117) 08/02/2017 https://www.trialregister.nl/trial/6117.

Non-Invasive Screen Exposure Time Assessment Using Wearable Sensor and Object Detection.

Cumulative screen exposure has been increased due to the explosion of digital technology ownership in the past decade for all people, including children who face exposure related risks such as obesity, eye problems, and disrupted sleep. Screen exposure is linked to physical and mental health risks among both children and adults. Current methods of screen exposure assessment have their limitations, mostly in the prospective of objectiveness, robustness, and invasiveness. In this paper, we propose a novel method to measure screen exposure time using a wearable sensor and computer vision technology. We use a customized, lightweight, wearable senor to capture egocentric images and use deep learning-based object detection module to identify the existence of electronic screens. The duration of screen exposure is further estimated using post-processing technology to filter consecutive frames regarding to the screen usage. Our method is non-invasive and robust, providing an objective and accurate means to screen exposure measurement. We conduct experiments on various environments to identify the existence of three types of screens and duration of screen exposure. The experimental results demonstrate the feasibility of automatically assessing screen time exposure and great potential to be applied in large scale experiments for behavioral study.

Is faster better? An economic evaluation of rapid and ultra-rapid genomic testing in critically ill infants and children.

PURPOSE: To evaluate whether the additional cost of providing increasingly faster genomic results in pediatric critical care is outweighed by reductions in health care costs and increases in personal utility. METHODS: Hospital costs and medical files from a cohort of 40 children were analyzed. The health economic impact of rapid and ultra-rapid genomic testing, with and without early initiation, relative to standard genomic testing was evaluated. RESULTS: Shortening the time to results led to substantial economic and personal benefits. Early initiation of ultra-rapid genomic testing was the most cost-beneficial strategy, leading to a cost saving of AU$26,600 per child tested relative to standard genomic testing and a welfare gain of AU$12,000 per child tested. Implementation of early ultra-rapid testing of critically ill children is expected to lead to an annual cost saving of AU$7.3 million for the Australian health system and an aggregate welfare gain of AU$3.3 million, corresponding to a total net benefit of AU$10.6 million. CONCLUSION: Early initiation of ultra-rapid genomic testing can offer substantial economic and personal benefits. Future implementation of rapid genomic testing programs should focus not only on optimizing the laboratory workflow to achieve a fast turnaround time but also on changing clinical practice to expedite test initiation.

It took a pandemic: Perspectives on impact, stress, and telehealth from caregivers of people with autism.

Shelter in place mandates due to the COVID-19 pandemic left caregivers to determine how to best meet the therapeutic requirements of their children with autism spectrum disorder (ASD). Understanding the challenges faced by families, and their experiences using telehealth for the first time, may help make services sustainable in future public health emergencies. A sample of 70 caregivers of people with ASD from across the US completed an anonymous online survey. Results indicate that impaired emotion regulation was a primary contributor of parent-reported stress for persons with ASD during the pandemic, while loss of established structure and routine contributed to parental stress. Nearly half the sample reported using telehealth for the first time. Many caregivers were appreciative that telehealth permitted continuation of services, but expressed concerns about limited effectiveness due in part to their children's social communication problems.

Assessment and Treatment of Emotion Regulation Impairment in Autism Spectrum Disorder Across the Life Span: Current State of the Science and Future Directions.

Emotion regulation (ER) is the ability to modify arousal and emotional reactivity to achieve goals and maintain adaptive behaviors. ER impairment in autism spectrum disorder (ASD) is thought to underlie many problem behaviors, co-occurring psychiatric symptoms, and social impairment, and yet is largely unaddressed both clinically and in research. There is a critical need to develop ER treatment and assessment options for individuals with ASD across the life span, given the multitude of downstream effects on functioning. This article summarizes the current state of science in ER assessment and treatment and identifies the most promising measurement options and treatments.

Utility of an Observational Social Skill Assessment as a Measure of Social Cognition in Autism.

Models of impaired social competence in autism spectrum disorder (ASD) highlight deficits in social cognition and social behavior. The Contextual Assessment of Social Skills (CASS) is a laboratory-based assessment of conversation ability in which participants interact with trained confederates who act interested (CASS-I) and bored (CASS-B), sequentially. The increased ecological validity of the CASS allows for better generalization to real-world social situations. Participants' perceptions of confederate behavior, assessed by the CASS Conversation Rating Scale (CRS), might offer additional utility as a metric of social cognition. The current study examined CASS confederate behavior (adherence to interested or bored condition) and both internal validity and convergent validity of the CASS as a measure of social behavior and social cognition. Fifty adolescents with ASD participated as part of a multisite randomized clinical trial. Adherence ratings were consistent across gender and site, with interested confederates significantly out-performing bored confederates. The ability to distinguish between interested and bored confederates was positively associated with CASS social behavior and social cognition tasks, although social behavior during the CASS was not consistently associated with parent-rated social behavior. Controlling for confederate behavior did not significantly alter these associations. Findings demonstrate strong internal validity of the CASS and, partially, external validity of the CASS as a measure of social cognition. Findings highlight nuanced differences in social behavior and social cognition. The CASS shows promise as an outcome measure for clinical interventions and should be incorporated into a multimethod battery to assess social competence in individuals with ASD. LAY SUMMARY: Social cognition and social behavior should be studied together to examine social competence in youth with autism. The Contextual Assessment of Social Skills (CASS), a behavioral observation measure, shows promise toward this end; findings suggest the CASS taps social cognition and social behavior when administered alongside a participant rating scale of their conversation partner's engagement. Continued research, including examination of the CASS, may inform best practices in comprehensive assessment of social competence in autism. Autism Res 2021, 14: 709-719. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

Specialized primary care medical home: A positive impact on continuity of care among autistic adults.

LAY ABSTRACT: There is a nationally recognized need for innovative healthcare delivery models to improve care continuity for autistic adults as they age out of pediatric and into adult healthcare systems. One possible model of care delivery is called the "medical home". The medical home is not a residential home, but a system where a patient's healthcare is coordinated through a primary care physician to ensure necessary care is received when and where the patient needs it. We compared the continuity of care among autistic adult patients at a specialized primary care medical home designed to remove barriers to care for autistic adults, called the CAST, to matched national samples of autistic adults with private insurance or Medicare. Continuity of primary care among CAST patients was significantly better than that of matched national samples of autistic adult Medicare beneficiaries and similar to that of privately insured autistic adults. Our findings suggest that medical homes, like CAST, are a promising solution to improve healthcare delivery for the growing population of autistic adults.

Race, gender, and scholarly impact: Disparities for women and faculty of color in clinical psychology.

OBJECTIVE: We sought to determine if gender and race are associated with scientific impact, scholarly productivity, career advancement, and prestige. METHODS: Publicly available data on publications, h-index, advancement, and prestige were assessed across core faculty in all American Psychological Association-accredited clinical psychology programs at R1 institutions in the United States (87 programs, 918 scientists). RESULTS: There were significant effects of both gender and race on productivity and impact, which were most apparent among the most senior faculty. Men and white faculty in associate and full professor ranks had higher scholarly productivity and impact. Among associate professors, men were more likely to get tenure earlier, even when controlling for scientific impact (h-index). Neither gender nor race was associated with prestige among full professors. CONCLUSION: These findings, along with under-representation of non-White faculty across levels (11.2%) and women at the full professor level (42.8%), suggest disparities in academic clinical psychology that must be addressed.

A cost-effectiveness analysis of genomic sequencing in a prospective versus historical cohort of complex pediatric patients.

PURPOSE: Cost-effectiveness evaluations of first-line genomic sequencing (GS) in the diagnosis of children with genetic conditions are limited by the lack of well-defined comparative cohorts. We sought to evaluate the cost-effectiveness of early GS in pediatric patients with complex monogenic conditions compared with a matched historical cohort. METHODS: Data, including investigation costs, were collected in a prospective cohort of 92 pediatric patients undergoing singleton GS over an 18-month period (2016-2017) with two of the following: a condition with high mortality, multisystem disease involving three or more organs, or severe limitation of daily function. Comparative data were collected in a matched historical cohort who underwent traditional investigations in the years 2012-2013. RESULTS: GS yielded a diagnosis in 42% while traditional investigations yielded a diagnosis in 23% (p = 0.003). A change in management was experienced by 74% of patients diagnosed following GS, compared with 32% diagnosed following traditional investigations. Singleton GS at a cost of AU$3100 resulted in a mean saving per person of AU$3602 (95% confidence interval [CI] AU$2520-4685). Cost savings occurred across all investigation subtypes and were only minimally offset by clinical management costs. CONCLUSION: GS in complex pediatric patients saves significant costs and doubles the diagnostic yield of traditional approaches.

Preoperative continuity of care and its relationship with cost of hepatopancreatic surgery.

BACKGROUND: Continuity of care may be associated with health care outcomes and costs. The objective of the current study was to characterize the impact of continuity of care on perioperative outcomes, as well as on cost of care, among Medicare beneficiaries undergoing hepatopancreatic resection. METHODS: Patients with a minimum of 4 outpatient visits in the year before hepatopancreatic surgery were identified in the Medicare claims data. The Bice-Boxerman index was used to calculate continuity of care. The association of continuity of care and expenditures was assessed using a multivariable gamma regression with a log link. RESULTS: Among 25,698 Medicare beneficiaries who underwent a hepatopancreatic surgical procedure (hepatectomy: n = 10,679, 41.6%, pancreatectomy: n = 15,019, 58.4%), median patient age was 72 years (interquartile range: 68-77). Overall continuity of care was poor as the median continuity of care was 0.17 (0.10-0.29). Median total surgical costs were higher among patients in the lowest continuity-of-care quartile (continuity of care1st quartile: $25,500 [interquartile range, $18,100-$41,800]) compared with patients in the highest continuity-of-care quartile (continuity of care4th quartile: $22,700 [interquartile range, $17,100-$38,400]). Among patients undergoing hepatic resection, an increase in continuity of care of 0.2 was associated with decreased costs of 5.1% (95% confidence interval: -6.3% to -3.8%) compared with a decrease of 2.5% (95% confidence interval: -3.7% to -1.2%) among pancreatic resection patients. CONCLUSION: Continuity of care in the year before surgery was associated with total cost of surgery-including the cost of the index hospitalization and the total 90-day postdischarge costs. Relative to patients with a continuity of care = 0, indicating complete fragmentation of a patient's outpatient health care, patients with a continuity of care = 0.60 had 12.1% lower total surgical costs.

Association of Body Mass Index With Coronary Artery Calcium and Subsequent Cardiovascular Mortality: The Coronary Artery Calcium Consortium.

BACKGROUND: Obesity is associated with higher risk for coronary artery calcium (CAC), but the relationship between body mass index (BMI) and mortality is complex and frequently paradoxical. METHODS: We analyzed BMI, CAC, and subsequent mortality using data from the CAC Consortium, a multi-centered cohort of individuals free of established cardiovascular disease (CVD) who underwent CAC testing. Mortality was assessed through linkage to the Social Security Death Index and cause of death from the National Death Index. Multivariable logistic regression was used to determine odds ratios for the association of clinically relevant BMI categories and prevalent CAC. Cox proportional hazards regression modeling was used to determine hazard ratios for coronary heart disease, CVD, and all-cause mortality according to categories of BMI and CAC. RESULTS: Our sample included 36 509 individuals, mean age 54.1 (10.3) years, 34.4% female, median BMI 26.6 (interquartile range, 24.1-30.1), 46.6% had zero CAC, and 10.5% had CAC ≥400. Compared with individuals with normal BMI, the multivariable adjusted odds of CAC >0 were increased in those overweight (odds ratio, 1.13 [95% CI, 1.1-1.2]) and obese (odds ratio, 1.5 [95% CI, 1.4-1.6]). Over a median follow-up of 11.4 years, there were 1550 deaths (4.3%). Compared with normal BMI, obese individuals had a higher risk of coronary heart disease, CVD, and all-cause mortality while overweight individuals, despite a higher odds of CAC, showed no significant increase in mortality. In a sex-stratified analysis, the increase in coronary heart disease, CVD, and all-cause mortality in obese individuals appeared largely limited to men, and there was a lower risk of all-cause mortality in overweight women (hazard ratio, 0.79 [95% CI, 0.63-0.98]). CONCLUSIONS: In a large sample undergoing CAC scoring, obesity was associated with a higher risk of CAC and subsequent coronary heart disease, CVD, and all-cause mortality. However, overweight individuals did not have a higher risk of mortality despite a higher risk for CAC.

Assessment and Treatment of Emotion Regulation Impairment in Autism Spectrum Disorder Across the Life Span: Current State of the Science and Future Directions.

Emotion regulation (ER) is the ability to modify arousal and emotional reactivity to achieve goals and maintain adaptive behaviors. ER impairment in autism spectrum disorder (ASD) is thought to underlie many problem behaviors, co-occurring psychiatric symptoms, and social impairment, and yet is largely unaddressed both clinically and in research. There is a critical need to develop ER treatment and assessment options for individuals with ASD across the life span, given the multitude of downstream effects on functioning. This article summarizes the current state of science in ER assessment and treatment and identifies the most promising measurement options and treatments.

Assessing post-discharge costs of hepatopancreatic surgery: an evaluation of Medicare expenditure.

BACKGROUND: The true cost of liver and pancreatic surgery may not be completely ascertained by examining costs associated solely with the index hospitalization. We sought to assess post-discharge costs related to liver and pancreatic surgery after the index hospitalization. METHODS: We identified Medicare beneficiaries who underwent liver and pancreatic resection between 2013 and 2015. To assess post-discharge costs, costs were assessed for the following: all inpatient readmissions associated with an operative complication, follow-up outpatient visits with their operating surgeon, and use of skilled nursing facilities, hospice, and home health care within 90 days of discharge. RESULTS: Among the 21,737 patients who underwent either pancreatic or liver resection, the median cost of the index admission was $20,500 (interquartile range: $16,100-$34,300) (pancreas median: $22,100; interquartile range: $16,800-$36,500 vs liver median: $19,100; interquartile range: $15,100-$29,000). Approximately 30% (n = 6,435) had an all-cause readmission; more than half of readmissions (55.8%; n = 3,589) were related to an operative complication. Skilled nursing facilities and home health care services were utilized by 18.5% (n = 4,016) and 42.6% (n = 9,259) of patients, respectively. In total, nearly 75% of patients had additional, post-discharge hidden costs associated with their operative episode of care (n = 15,733: 72.4%). Male sex (95% confidence interval: 1.15-1.30) and black/African American race (95% confidence interval: 1.02-1.34) were associated with greater odds of post-discharge costs (both <0.05). CONCLUSION: Nearly 3 out of 4 patients who underwent a liver or pancreatic resection had post-discharge costs. Male and black/African American patients had greater odds of incurring post-discharge costs. As payers move to more bundled care payment models, strategies aimed at bending the cost curve associated with both the in-hospital, as well as the post-discharge setting, are needed.

Dedicated Cancer Centers are More Likely to Achieve a Textbook Outcome Following Hepatopancreatic Surgery.

INTRODUCTION: The aim of the current study is to assess rates of textbook outcome (TO) among Medicare beneficiaries undergoing hepatopancreatic (HP) surgery for cancer at dedicated cancer centers (DCCs) and National Cancer Institute affiliated cancer centers (NCI-CCs) versus non-DCC non-NCI hospitals. PATIENTS AND METHODS: Medicare Inpatient Standard Analytic Files were utilized to identify patients undergoing HP surgery between 2013 and 2017. TO was defined as no postoperative surgical complications, no 90-day mortality, no prolonged length of hospital stay, and no 90-day readmission after discharge. RESULTS: Among 21,234 Medicare patients, 8.2% patients underwent surgery at DCCs whereas 32.1% underwent surgery at NCI-CCs and 59.7% underwent an operation at neither DCCs nor NCI-CCs. Although DCCs more often cared for patients with severe comorbidities [Charlson score > 5: DCCs, 1195 (68.9%), NCI-CCs, 3687 (54.1%), others, 3970 (31.3%); p < 0.001], DCCs achieved higher rates of TO compared with NCI-CCs and other US hospitals. Interestingly, DCCs were more likely to perform surgery with a minimally invasive approach versus NCI-CCs and other US hospitals (17.0%, n = 295, vs. 12.6%, n = 856 vs. 11.9%, n = 1504, p < 0.001). On multivariable analysis, patients undergoing liver surgery at DCCs had 31% and 36% higher odds of achieving TO compared with NCI-CCs and other US hospitals, respectively. Medicare expenditure was substantially lower for patients achieving TO at DCCs compared with patients who achieved a TO at NCI-CCs. CONCLUSIONS: Even though DCCs more frequently took care of patients with high comorbidity burden, the likelihood of achieving TO for HP surgery at DCCs was higher compared with NCI-CCs and other US hospitals. The data suggest that DCCs provide higher-value surgical care for patients with HP malignancies.

Assessment of utilization efficiency using machine learning techniques: A study of heterogeneity in preoperative healthcare utilization among super-utilizers.

INTRODUCTION: In the United States, 5% of patients represent up to 55% of all health care costs. This study sought to define healthcare utilization patterns among super-utilizers, as well as assess possible variation in patient outcomes. METHODS: Medicare super-utilizers undergoing either a total hip or knee arthroplasty were identified and entered into a cluster analysis using annual preoperative charges to identify distinct patterns of utilization. RESULTS: Among 19,522 super-utilizers who underwent THA or TKA, there was a marked heterogeneity in overall utilization with 5 distinct clusters of utilization patterns. Of note, comorbidity burden was similar among the 5 clusters. Patient outcomes also varied by Cluster type, ranging from 6.9% to 16.5% experiencing complications and 1.0%-3.2% experiencing 90-day mortality. CONCLUSION: While previous studies have suggested that super-utilizers are a homogenous group of patients, the current study demonstrated a large degree of heterogeneity within super-utilizers. Variations in utilization patterns were associated with postoperative outcomes and subsequent health care costs.

Interaction of Surgeon Volume and Nurse-to-Patient Ratio on Post-operative Outcomes of Medicare Beneficiaries Following Pancreaticoduodenectomy.

BACKGROUND: We sought to assess the effect of nurse-to-patient ratio on outcomes with a focus on defining whether nurse-to-patient ratio altered outcomes relative to pancreaticoduodenectomy (PD) surgeon specific volume. METHODS: Medicare SAFs from 2013-2015 were used to identify patients who underwent PD. Nurse-to-patient ratio, PD specific surgeon volume were stratified. Association of factors associated with short term outcomes was evaluated. RESULTS: Overall, 6668 patients (median age 73, IQR 68-77; 52.8% male) were identified. The median annual PD volume of surgeons in the highest volume tier was 24 (IQR 21-29), whereas surgeons in the lowest tier performed 2 PDs annually (IQR 1-3) (p < 0.001). Compared with hospitals that had the highest nurse-to-patient ratio tier, patients at hospitals with the lowest nurse-to-patient ratio tier were 26% more likely to have a complication (OR 1.26, 95% CI 1.02-1.55). Additionally, patients of surgeons in the lowest tier had 43% greater odds of suffering a complication compared to patients of surgeons in the highest tier (OR 1.43, 95% CI 1.11-1.84). However, patients who underwent a PD by a surgeon within the lowest tier had similar odds of a complication irrespective of nurse-to-patient ratio (OR 1.34, 95% CI 0.97-1.86). CONCLUSION: Compared with patients who underwent an operation by a surgeon in highest PD volume tier, patients treated by surgeons in the lowest tier had higher odds of post-operative complications which was not mitigated by a higher nurse-to-patient ratio.