Leveraging the adolescent brain cognitive development study to improve behavioral prediction from neuroimaging in smaller replication samples.

Neuroimaging is a popular method to map brain structural and functional patterns to complex human traits. Recently published observations cast doubt upon these prospects, particularly for prediction of cognitive traits from structural and resting state functional magnetic resonance imaging (MRI). We leverage baseline data from thousands of children in the Adolescent Brain Cognitive DevelopmentSM Study to inform the replication sample size required with univariate and multivariate methods across different imaging modalities to detect reproducible brain-behavior associations. We demonstrate that by applying multivariate methods to high-dimensional brain imaging data, we can capture lower dimensional patterns of structural and functional brain architecture that correlate robustly with cognitive phenotypes and are reproducible with only 41 individuals in the replication sample for working memory-related functional MRI, and ~ 100 subjects for structural and resting state MRI. Even with 100 random re-samplings of 100 subjects in discovery, prediction can be adequately powered with 66 subjects in replication for multivariate prediction of cognition with working memory task functional MRI. These results point to an important role for neuroimaging in translational neurodevelopmental research and showcase how findings in large samples can inform reproducible brain-behavior associations in small sample sizes that are at the heart of many research programs and grants.

Conjoint Analysis of Telemedicine Preferences for Hypertension Management Among Adult Patients.

Background: Telemedicine has been differentially utilized by different demographic groups during COVID-19, exacerbating inequities in health care. We conducted conjoint and latent class analyses to understand factors that shape patient preferences for hypertension management telemedicine appointments. Methods: We surveyed 320 adults, oversampling participants from households that earned <$50K per year (77.2%) and speak a language other than English at home (68.8%). We asked them to choose among 2 hypothetical appointments through 12 conjoint tasks measuring 6 attributes. Individual utilities for attributes were constructed using logit estimation, and latent classes were identified and compared by demographic and clinical characteristics. Results: Respondents preferred in-person visits (0.353, standard error [SE] = 0.039) and video appointments conducted through a secure patient portal (0.002, SE = 0.040). Respondents also preferred seeing a clinician with whom they have an established relationship (0.168, SE = 0.021). We found four latent classes: "in-person" (26.5% of participants) who strongly weighted in-person appointments, "cost conscious" (8.1%) who prioritized the lowest copay ($0 to $10), "expedited" (19.7%) who prioritized getting the earliest appointment possible (same/next day or at least within the next week), and "comprehensive" (45.6%) who had preferences for in-person care and telemedicine appointments through a secure portal, low copayments, and the ability to see a familiar clinician. Conclusions: Appointment preferences for hypertension management can be segmented into four groups that prioritize (1) in-person care, (2) low copayments, (3) expedited care, and (4) balanced preferences for in-person and telemedicine appointments. Evidence is needed to clarify whether aligning appointment offerings with patients' preferences can improve care quality, equity, and efficiency.

Hospital Characteristics Associated With Clinically Integrated Network Participation.

BACKGROUND: Increased integration of physician organizations and hospitals into health systems has not necessarily improved clinical integration or patient outcomes. However, federal regulators have issued favorable opinions for clinically integrated networks (CINs) as a way to pursue coordination between hospitals and physicians. Hospital organizational affiliations, including independent practice associations (IPA), physician-hospital organizations (PHOs), and accountable care organizations (ACOs), may support CIN participation. No empirical evidence, however, exists about factors associated with CIN participation. METHODS: Data from the 2019 American Hospital Association survey (n = 4405) were analyzed to quantify hospital CIN participation. Multivariable logistic regression models were estimated to examine whether IPA, PHO, and ACO affiliations were associated with CIN participation, controlling for market factors and hospital characteristics. RESULTS: In 2019, 34.6% of hospitals participated in a CIN. Larger, not-for-profit, and metropolitan hospitals were more likely to participate in CINs. In adjusted analyses, hospitals participating in CINs were more likely to have an IPA (9.5% points, P < 0.001), a PHO (6.1% points, P < 0.001), and ACO (19.3% points, P < 0.001) compared with hospitals not participating in a CIN. CONCLUSIONS: Over one-third of hospitals participate in a CIN, despite limited evidence about their effectiveness in delivering value. Results suggest that CIN participation may be a response to integrative norms. Future work should attempt to better define CIN participation and strive to disentangle overlapping organizational participation.

Telehealth Use, Care Continuity, and Quality: Diabetes and Hypertension Care in Community Health Centers Before and During the COVID-19 Pandemic.

BACKGROUND: Community health centers (CHCs) pivoted to using telehealth to deliver chronic care during the coronavirus COVID-19 pandemic. While care continuity can improve care quality and patients' experiences, it is unclear whether telehealth supported this relationship. OBJECTIVE: We examine the association of care continuity with diabetes and hypertension care quality in CHCs before and during COVID-19 and the mediating effect of telehealth. RESEARCH DESIGN: This was a cohort study. PARTICIPANTS: Electronic health record data from 166 CHCs with n=20,792 patients with diabetes and/or hypertension with ≥2 encounters/year during 2019 and 2020. METHODS: Multivariable logistic regression models estimated the association of care continuity (Modified Modified Continuity Index; MMCI) with telehealth use and care processes. Generalized linear regression models estimated the association of MMCI and intermediate outcomes. Formal mediation analyses assessed whether telehealth mediated the association of MMCI with A1c testing during 2020. RESULTS: MMCI [2019: odds ratio (OR)=1.98, marginal effect=0.69, z=165.50, P<0.001; 2020: OR=1.50, marginal effect=0.63, z=147.73, P<0.001] and telehealth use (2019: OR=1.50, marginal effect=0.85, z=122.87, P<0.001; 2020: OR=10.00, marginal effect=0.90, z=155.57, P<0.001) were associated with higher odds of A1c testing. MMCI was associated with lower systolic (ß=-2.90, P<0.001) and diastolic blood pressure (ß=-1.44, P<0.001) in 2020, and lower A1c values (2019: ß=-0.57, P=0.007; 2020: ß=-0.45, P=0.008) in both years. In 2020, telehealth use mediated 38.7% of the relationship between MMCI and A1c testing. CONCLUSIONS: Higher care continuity is associated with telehealth use and A1c testing, and lower A1c and blood pressure. Telehealth use mediates the association of care continuity and A1c testing. Care continuity may facilitate telehealth use and resilient performance on process measures.

Shared Decision-making Lowers Medical Expenditures and the Effect Is Amplified in Racially-Ethnically Concordant Relationships.

BACKGROUND: Racial-ethnic disparities are pervasive in health care. One mechanism that may underlie disparities is variation in shared decision-making (SDM), which encompasses high-quality clinician-patient communication, including deliberative discussions about treatment options. OBJECTIVES: To determine whether SDM has causal effects on outcomes and whether these effects are stronger within racial-ethnic concordant clinician-patient relationships. RESEARCH DESIGN: We use instrumental variables to estimate the causal effect of SDM on outcomes. SUBJECTS: A total of 60,584 patients from the 2003-2017 Integrated Public Use Microdata Series Medical Expenditure Panel Survey. Years 2018 and 2019 were excluded due to changes in the Medical Expenditure Panel Survey that omitted essential parts of the SDM index. MEASURES: Our key variable of interest is the SDM index. Outcomes included total, outpatient, and drug expenditures; physical and mental health; and the utilization of inpatient and emergency services. RESULTS: SDM lowers annual total health expenditures for all racial-ethnic groups, but this effect is only moderated among Black patients seen by Black clinicians, more than doubling in size relative to Whites. A similar SDM moderation effect also occurs for both Black patients seen by Black clinicians and Hispanic patients seen by Hispanic clinicians with regard to annual outpatient expenditures. There was no significant effect of SDM on self-reported physical or mental health. CONCLUSIONS: High-quality SDM can reduce health expenditures without negatively impacting overall physical or mental health, supporting a business case for health care organizations and systems to improve racial-ethnic clinician-patient concordance for Black and Hispanic patients.

A human neurodevelopmental model for Williams syndrome.

Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.

Understanding the distributional impacts of health insurance reform: Evidence from a consumer cost-sharing program.

We examine the heterogeneous effects of reference pricing, a health insurance reform introduced by the California Public Employees' Retirement System (CalPERS), on the distribution of spending by patients and insurers. Using medical claims data for CalPERS and a comparison group not subject to reference pricing, we use the changes-in-changes approach to estimate the quantile treatment effects of the program across different medical procedures. We find that the quantile treatment effects vary across the patient spending distributions, with a range of positive and negative estimates of the QTE, depending on the medical procedure considered. However, across all procedures, the insurer's spending distributions tend to shift left, with the largest reductions occurring in the right-tail of the spending distributions. These effects are not captured by mean estimates but have important policy implications.

Association of Reference Pricing with Drug Selection and Spending.

Background In the United States, prices for therapeutically similar drugs vary widely, which has prompted efforts by public and private insurers to steer patients toward the lower-priced options. Under reference pricing, the insurer or employer establishes a maximum contribution it will make toward the price of a drug or procedure, and the patient pays the remainder. Methods We used difference-in-differences multivariable regression methods to analyze changes in prescriptions and pricing for 1302 drugs in 78 therapeutic classes in the United States, before and after implementation of reference pricing by an alliance of private employers. We assessed trends for the study group relative to those for an employee group that was not subject to reference pricing. The study included 1,122,741 prescriptions that were reimbursed during the period from 2010 through 2014. Results Implementation of reference pricing was associated with a higher percentage of prescriptions that were filled for the lowest-priced reference drug within its therapeutic class (difference in probability, 7.0 percentage points; 95% confidence interval [CI], 4.0 to 9.9), a lower average price paid per prescription (-13.9%; 95% CI, -23.8 to -2.7), and a higher rate of copayment by patients (5.2%; 95% CI, 0.2 to 10.4) than in the comparison group. During the first 18 months after implementation, spending for employers was $1.34 million lower and the amount of copayments for employees was $0.12 million higher than in the comparison group. Conclusions Implementation of reference pricing was associated with significant changes in drug selection and spending for a population of patients covered by employment-based insurance in the United States. (Funded by the Agency for Healthcare Research and Quality and the Genentech Foundation.).

Patterns of structural lateralization in cortical language areas of older adolescents.

Structural lateralization of cortical language areas has been extensively studied in the past, with the conclusion that there is a predominant left lateralization in the majority of typically developing adolescents. However, lateralization in this age group has often been examined using cortical volumetric measures, without taking into account the independence of surface area and thickness. Utilizing structural MRI data in a relatively large sample size, the lateralization of cortical volume, surface area, and thickness was analysed across regions of interest (ROIs) known to support language processing in 118 typically developing adolescents, ages 13;9 to 18;9 using a laterality index. Results showed that the laterality index scores for volume and surface area were more strongly correlated than volume and thickness. Results also showed that not all language regions were left lateralized, with some ROIs being significantly right lateralized. Results also showed that surface area and thickness did not always share direction of lateralization. Taken together these results indicate that cortical ROIs supporting language are not all strongly left lateralized in adolescents. These data also show that cortical surface area and cortical thickness need to be treated independently in future studies characterizing language and lateralization in the adolescent brain.

A multisample study of longitudinal changes in brain network architecture in 4-13-year-old children.

Recent advances in human neuroimaging research have revealed that white-matter connectivity can be described in terms of an integrated network, which is the basis of the human connectome. However, the developmental changes of this connectome in childhood are not well understood. This study made use of two independent longitudinal diffusion-weighted imaging data sets to characterize developmental changes in the connectome by estimating age-related changes in fractional anisotropy (FA) for reconstructed fibers (edges) between 68 cortical regions. The first sample included 237 diffusion-weighted scans of 146 typically developing children (4-13 years old, 74 females) derived from the Pediatric Longitudinal Imaging, Neurocognition, and Genetics (PLING) study. The second sample included 141 scans of 97 individuals (8-13 years old, 62 females) derived from the BrainTime project. In both data sets, we compared edges that had the most substantial age-related change in FA to edges that showed little change in FA. This allowed us to investigate if developmental changes in white matter reorganize network topology. We observed substantial increases in edges connecting peripheral and a set of highly connected hub regions, referred to as the rich club. Together with the observed topological differences between regions connecting to edges showing the smallest and largest changes in FA, this indicates that changes in white matter affect network organization, such that highly connected regions become even more strongly imbedded in the network. These findings suggest that an important process in brain development involves organizing patterns of inter-regional interactions. Hum Brain Mapp 39:157-170, 2018. © 2017 Wiley Periodicals, Inc.