NPSV-deep: a deep learning method for genotyping structural variants in short read genome sequencing data.

MOTIVATION: Structural variants (SVs) play a causal role in numerous diseases but can be difficult to detect and accurately genotype (determine zygosity) with short-read genome sequencing data (SRS). Improving SV genotyping accuracy in SRS data, particularly for the many SVs first detected with long-read sequencing, will improve our understanding of genetic variation. RESULTS: NPSV-deep is a deep learning-based approach for genotyping previously reported insertion and deletion SVs that recasts this task as an image similarity problem. NPSV-deep predicts the SV genotype based on the similarity between pileup images generated from the actual SRS data and matching SRS simulations. We show that NPSV-deep consistently matches or improves upon the state-of-the-art for SV genotyping accuracy across different SV call sets, samples and variant types, including a 25% reduction in genotyping errors for the Genome-in-a-Bottle (GIAB) high-confidence SVs. NPSV-deep is not limited to the SVs as described; it improves deletion genotyping concordance a further 1.5 percentage points for GIAB SVs (92%) by automatically correcting imprecise/incorrectly described SVs. AVAILABILITY AND IMPLEMENTATION: Python/C++ source code and pre-trained models freely available at https://github.com/mlinderm/npsv2.

After 50 Years, Health Professional Shortage Areas Had No Significant Impact On Mortality Or Physician Density.

Since 1965, the US federal government has incentivized physicians to practice in high-need areas of the country through the designation of Health Professional Shortage Areas (HPSAs). Despite its being in place for more than half a century and directing more than a billion dollars annually, there is limited evidence of the HPSA program's effectiveness at reducing geographic disparities in access to care and health outcomes. Using a generalized difference-in-differences design with matching, we found no statistically significant changes in mortality or physician density from 1970 to 2018 after a county-level HPSA designation. As a result, we found that 73 percent of counties designated as HPSAs remained physician shortage areas for at least ten years after their inclusion in the program. Fundamental improvements to the program's design and incentive structure may be necessary for it to achieve its intended results.

What Difference Does a Health Plan Make? Evidence from Random Plan Assignment in Medicaid.

Exploiting the random assignment of Medicaid beneficiaries to managed care plans, we find substantial plan-specific spending effects despite plans having identical cost sharing. Enrollment in the lowest-spending plan reduces spending by at least 25%-primarily through quantity reductions-relative to enrollment in the highest-spending plan. Rather than reducing "wasteful" spending, lower-spending plans broadly reduce medical service provision-including the provision of low-cost, high-value care-and worsen beneficiary satisfaction and health. Consumer demand follows spending: a 10 percent increase in plan-specific spending is associated with a 40 percent increase in market share. These facts have implications for the government's contracting problem and program cost growth.

Association between Medicare eligibility at age 65 years and in-hospital treatment patterns and health outcomes for patients with trauma: regression discontinuity approach.

OBJECTIVE: To determine whether health systems in the United States modify treatment or discharge decisions for otherwise similar patients based on health insurance coverage. DESIGN: Regression discontinuity approach. SETTING: American College of Surgeons' National Trauma Data Bank, 2007-17. PARTICIPANTS: Adults aged between 50 and 79 years with a total of 1 586 577 trauma encounters at level I and level II trauma centers in the US. INTERVENTIONS: Eligibility for Medicare at age 65 years. MAIN OUTCOME MEASURES: The main outcome measure was change in health insurance coverage, complications, in-hospital mortality, processes of care in the trauma bay, treatment patterns during hospital admission, and discharge locations at age 65 years. RESULTS: 1 586 577 trauma encounters were included. At age 65, a discontinuous increase of 9.6 percentage points (95% confidence interval 9.1 to 10.1) was observed in the share of patients with health insurance coverage through Medicare at age 65 years. Entry to Medicare at age 65 was also associated with a decrease in length of hospital stay for each encounter, of 0.33 days (95% confidence interval -0.42 to -0.24 days), or nearly 5%), which coincided with an increase in discharges to nursing homes (1.56 percentage points, 95% confidence interval 0.94 to 2.16 percentage points) and transfers to other inpatient facilities (0.57 percentage points, 0.33 to 0.80 percentage points), and a large decrease in discharges to home (1.99 percentage points, -2.73 to -1.27 percentage points). Relatively small (or no) changes were observed in treatment patterns during the patients' hospital admission, including no changes in potentially life saving treatments (eg, blood transfusions) or mortality. CONCLUSIONS: The findings suggest that differences in treatment for otherwise similar patients with trauma with different forms of insurance coverage arose during the discharge planning process, with little evidence that health systems modified treatment decisions based on patients' coverage.

Excess Death Rates for Republican and Democratic Registered Voters in Florida and Ohio During the COVID-19 Pandemic.

Importance: There is evidence that Republican-leaning counties have had higher COVID-19 death rates than Democratic-leaning counties and similar evidence of an association between political party affiliation and attitudes regarding COVID-19 vaccination; further data on these rates may be useful. Objective: To assess political party affiliation and mortality rates for individuals during the initial 22 months of the COVID-19 pandemic. Design, Setting, and Participants: A cross-sectional comparison of excess mortality between registered Republican and Democratic voters between March 2020 and December 2021 adjusted for age and state of voter registration was conducted. Voter and mortality data from Florida and Ohio in 2017 linked to mortality records for January 1, 2018, to December 31, 2021, were used in data analysis. Exposures: Political party affiliation. Main Outcomes and Measures: Excess weekly deaths during the COVID-19 pandemic adjusted for age, county, party affiliation, and seasonality. Results: Between January 1, 2018, and December 31, 2021, there were 538 159 individuals in Ohio and Florida who died at age 25 years or older in the study sample. The median age at death was 78 years (IQR, 71-89 years). Overall, the excess death rate for Republican voters was 2.8 percentage points, or 15%, higher than the excess death rate for Democratic voters (95% prediction interval [PI], 1.6-3.7 percentage points). After May 1, 2021, when vaccines were available to all adults, the excess death rate gap between Republican and Democratic voters widened from -0.9 percentage point (95% PI, -2.5 to 0.3 percentage points) to 7.7 percentage points (95% PI, 6.0-9.3 percentage points) in the adjusted analysis; the excess death rate among Republican voters was 43% higher than the excess death rate among Democratic voters. The gap in excess death rates between Republican and Democratic voters was larger in counties with lower vaccination rates and was primarily noted in voters residing in Ohio. Conclusions and Relevance: In this cross-sectional study, an association was observed between political party affiliation and excess deaths in Ohio and Florida after COVID-19 vaccines were available to all adults. These findings suggest that differences in vaccination attitudes and reported uptake between Republican and Democratic voters may have been factors in the severity and trajectory of the pandemic in the US.

Conditional cross-design synthesis estimators for generalizability in Medicaid.

While much of the causal inference literature has focused on addressing internal validity biases, both internal and external validity are necessary for unbiased estimates in a target population of interest. However, few generalizability approaches exist for estimating causal quantities in a target population that is not well-represented by a randomized study but is reflected when additionally incorporating observational data. To generalize to a target population represented by a union of these data, we propose a novel class of conditional cross-design synthesis estimators that combine randomized and observational data, while addressing their estimates' respective biases-lack of overlap and unmeasured confounding. These methods enable estimating the causal effect of managed care plans on health care spending among Medicaid beneficiaries in New York City, which requires obtaining estimates for the 7% of beneficiaries randomized to a plan and 93% who choose a plan, who do not resemble randomized beneficiaries. Our new estimators include outcome regression, propensity weighting, and double robust approaches. All use the covariate overlap between the randomized and observational data to remove potential unmeasured confounding bias. Applying these methods, we find substantial heterogeneity in spending effects across managed care plans. This has major implications for our understanding of Medicaid, where this heterogeneity has previously been hidden. Additionally, we demonstrate that unmeasured confounding rather than lack of overlap poses a larger concern in this setting.

In vivo Modulation of Intraocular and Intracranial Pressures Causes Nonlinear and Non-monotonic Deformations of the Lamina Cribrosa and Scleral Canal.

Purpose: To evaluate changes in monkey optic nerve head (ONH) morphology under acutely controlled intraocular pressure (IOP) and intracranial pressure (ICP). Methods: Seven ONHs from six monkeys were imaged via optical coherence tomography while IOP and ICP were maintained at one of 16 conditions. These conditions were defined by 4 levels for each pressure: low, baseline, high and very high. Images were processed to determine scleral canal area, aspect ratio, and planarity and anterior lamina cribrosa (ALC) shape index and curvature. Linear mixed effect models were utilized to investigate the effects of IOP, ICP and their interactions on ONH morphological features. The IOP-ICP interaction model was compared with one based on translaminar pressure difference (TLPD). Results: We observed complex, eye-specific, non-linear patterns of ONH morphological changes with changes in IOP and ICP. For all ONH morphological features, linear mixed effects models demonstrated significant interactions between IOP and ICP that were unaccounted for by TLPD. Interactions indicate that the effects of IOP and ICP depend on the other pressure. The IOP-ICP interaction model was a higher quality predictor of ONH features than a TLPD model. Conclusions: In vivo modulation of IOP and ICP causes nonlinear and non-monotonic changes in monkey ONH morphology that depend on both pressures and is not accounted for by a simplistic TLPD. These results support and extend prior findings. Translational Relevance: A better understanding of ICP's influence on the effects of IOP can help inform the highly variable presentations of glaucoma and effective treatment strategies.

Risk Adjustment And Promoting Health Equity In Population-Based Payment: Concepts And Evidence.

The objective of risk adjustment is not to predict spending accurately but to support the social goals of a payment system, which include equity. Setting population-based payments at accurate predictions risks entrenching spending levels that are insufficient to mitigate the impact of social determinants on health care use and effectiveness. Instead, to advance equity, payments must be set above current levels of spending for historically disadvantaged groups. In analyses intended to guide such reallocations, we found that current risk adjustment for the community-dwelling Medicare population overpredicts annual spending for Black and Hispanic beneficiaries by $376-$1,264. The risk-adjusted spending for these populations is lower than spending for White beneficiaries despite the former populations' worse risk-adjusted health and functional status. Thus, continued movement from fee-for-service to population-based payment models that omit race and ethnicity from risk adjustment (as current models do) should result in sizable resource reallocations and incentives that support efforts to address racial and ethnic disparities in care. We found smaller overpredictions for less-educated beneficiaries and communities with higher proportions of residents who are Black, Hispanic, or less educated, suggesting that additional payment adjustments that depart from predictive accuracy are needed to support health equity. These findings also suggest that adding social risk factors as predictors to spending models used for risk adjustment may be counterproductive or accomplish little.

Long-Term Stability of Coverage Among Michigan Medicaid Beneficiaries : A Cohort Study.

BACKGROUND: Medicaid, the primary source of insurance coverage for disadvantaged Americans, was originally designed as a temporary safety-net program. No studies have used long-run data to assess the recent use of the program by beneficiaries. OBJECTIVE: To assess patterns of short- and long-term enrollment among beneficiaries, using a 10-year longitudinal panel of Michigan Medicaid eligibility data. DESIGN: Primary analyses assessing trends in Medicaid enrollment among cohorts of existing and new beneficiaries. SETTING: Administrative records from Michigan Medicaid for the period 2011 to 2020. PARTICIPANTS: 3.97 million Medicaid beneficiaries. MEASUREMENTS: Short- and long-term enrollment in the program. RESULTS: The sample includes 3.97 million unique beneficiaries enrolled at some point between 2011 and 2020. Among a cohort of 1.23 million beneficiaries enrolled in 2011, over half (53%) were also enrolled in Medicaid in June 2020, spending, on average, two-thirds of that period (67%) on Medicaid. These beneficiaries, however, experienced substantial lapses in coverage, as only 25% were continuously enrolled throughout the period. Enrollment was less stable when assessed from the perspective of newly enrolled beneficiaries, of whom only 37% remained enrolled at the end of the study period. LIMITATION: Primary estimates from a single state. CONCLUSION: For many beneficiaries, Medicaid has served as their primary source of coverage for at least a decade. This pattern would justify increasing investments in the program to improve long-term health outcomes. PRIMARY FUNDING SOURCE: Self-funded.

State-Level Variation in Supplemental Maternity Kick Payments in Medicaid Managed Care.

This cross-sectional study assesses the prevalence and magnitude of state-level delivery event­triggered kick payments to Medicaid managed care plans and their association with delivery costs.

Stretch-Induced Uncrimping of Equatorial Sclera Collagen Bundles.

Stretch-induced collagen uncrimping underlies the nonlinear mechanical behavior of the sclera according to what is often called the process of recruitment. We recently reported experimental measurements of sclera collagen crimp and pressure-induced uncrimping. Our studies, however, were cross-sectional, providing statistical descriptions of crimp with no information on the effects of stretch on specific collagen bundles. Data on bundle-specific uncrimping is necessary to better understand the effects of macroscale input on the collagen microscale and tissue failure. Our goal in this project was to measure bundle-specific stretch-induced collagen uncrimping of sclera. Three goat eyes were cryosectioned sagittally (30 µm). Samples of equatorial sclera were isolated, mounted to a custom uni-axial stretcher and imaged with polarized light microscopy at various levels of clamp-to-clamp stretch until failure. At each stretch level, local strain was measured using image tracking techniques. The level of collagen crimping was determined from the bundle waviness, defined as the circular standard deviation of fiber orientation along a bundle. Eye-specific recruitment curves were then computed using eye-specific waviness at maximum stretch before sample failure to define fibers as recruited. Nonlinear mixed effect models were used to determine the associations of waviness to local strain and recruitment to clamp-to-clamp stretch. Waviness decreased exponentially with local strain (p < 0.001), whereas bundle recruitment followed a sigmoidal curve with clamp-to-clamp stretch (p < 0.001). Individual bundle responses to stretch varied substantially, but recruitment curves were similar across sections and eyes. In conclusion, uni-axial stretch caused measurable bundle-specific uncrimping, with the sigmoidal recruitment pattern characteristic of fiber-reinforced soft tissues.

Association Between Medicaid Managed Care Coverage of Substance Use Services and Treatment Utilization.

Importance: Medicaid insures a disproportionate share of adults with substance use disorder (SUD) and is thus uniquely positioned to facilitate access to care. Many enrollees receive coverage through Medicaid managed care (MMC) plans, which receive capitated payments in exchange for coverage of a defined set of benefits. Historically, coverage of substance use services has been carved out of MMC plans and financed fee-for-service (FFS) by state Medicaid programs, but in recent years, many states have opted to carve in this benefit. Little is known about whether MMC coverage of substance use services, relative to FFS coverage, is associated with changes in utilization. Objective: To examine the association between changes in MMC coverage of substance use services and admissions for substance use treatment. Design, Setting, and Participants: This cross-sectional study examined changes in admissions for substance use treatment in 2 states after coverage of substance use services was either carved into (Nebraska) or carved out of (Maryland) comprehensive MMC coverage. Synthetic control methods were used to compare changes in admissions between states that did and did not alter MMC coverage of substance use services. Data on substance use treatment admissions were obtained from the Treatment Episode Data Set-Admissions from 2010 to 2019. Exposures: Carve-outs or carve-ins of coverage for both inpatient and outpatient substance use services from comprehensive MMC coverage. Main Outcomes and Measures: Reported substance use treatment admissions per 100 000 residents and admissions by treatment type (ie, rehabilitation or residential, outpatient, and detoxification) per 100 000 residents. Results: Maryland's carve-out was associated with an additional mean 787.1 (95% CI, 624.6-1141.7) substance use admissions per 100 000 residents during 2015 and 2016, a relative increase of 104.4% (95% CI, 64.4%-154.1%) compared with its synthetic control. This increase was concentrated among changes in outpatient services utilization. In Nebraska, the carve-in was associated with a mean decrease of 97.2 (95% CI, -23.4 to 213.6) admissions per 100 000 residents, a relative decrease of 33.2% (95% CI, -54.1% to 29.6%) compared with its synthetic control and was concentrated primarily among admissions for detoxification services. Conclusions and Relevance: The results of this cross-sectional study suggest that carving out coverage of substance use services and financing them through FFS coverage may be associated with overall increases in treatment utilization but with heterogeneous associations across states and treatment types.

Performance Metrics of Substance Use Disorder Care Among Medicaid Enrollees in New York, New York.

Importance: There is limited evaluation of the performance of Medicaid managed care (MMC) private plans in covering substance use disorder (SUD) treatment. Objective: To compare the performance of MMC plans across 19 indicators of access, quality, and outcomes of SUD treatment. Design Setting and Participants: This cross-sectional study used administrative claims and mandatory assignment to plans of up to 159 016 adult Medicaid recipients residing in 1 of the 5 counties (boroughs) of New York, New York, from January 2009 to December 2017 to identify differences in SUD treatment access, patterns, and outcomes among different types of MMC plans. Data from the latest years were received from the New York State Department of Health in October 2019, and analysis began soon thereafter. Approximately 17% did not make an active choice of plan, and a subset of these (approximately 4%) can be regarded as randomly assigned. Exposures: Plan assignment. Main Outcomes and Measures: Percentage of the enrollees achieving performance measures across 19 indicators of access, process, and outcomes of SUD treatment. Results: Medicaid claims data from 159 016 adults (mean [SD] age, 35.9 [12.7] years; 74 261 women [46.7%]; 8746 [5.5%] Asian, 73 783 [46.4%] Black, and 40 549 [25.5%] White individuals) who were auto assigned to an MMC plan were analyzed. Consistent with national patterns, all plans achieved less than 50% (range, 0%-62.1%) on most performance measures. Across all plans, there were low levels of treatment engagement for alcohol (range, 0%-0.4%) and tobacco treatment (range, 0.8%-7.2%), except for engagement for opioid disorder treatment (range, 41.5%-61.4%). For access measures, 4 of the 9 plans performed significantly higher than the mean on recognition of an SUD diagnosis, any service use for the first time, and tobacco use screening. Of the process measures, total monthly expenditures on SUD treatment was the only measure for which plans differed significantly from the mean. Outcome measures differed little across plans. Conclusions and Relevance: The results of this cross-sectional study suggest the need for progress in engaging patients in SUD treatment and improvement in the low performance of SUD care and limited variation in MMC plans in New York, New York. Improvement in the overall performance of SUD treatment in Medicaid potentially depends on general program improvements, not moving recipients among plans.

Disparities in Health Care Spending and Utilization Among Black and White Medicaid Enrollees.

Importance: Administrative records indicate that more than half of the 80 million Medicaid enrollees identify as belonging to a racial and ethnic minority group. Despite this, disparities within the Medicaid program remain understudied. For example, we know of no studies examining racial differences in Medicaid spending, a potential measure of how equitably state resources are allocated. Objectives: To examine whether and to what extent there are differences in health care spending and utilization between Black and White enrollees in Medicaid. Design Setting and Participants: This cross-sectional study used calendar year 2016 administrative data from 3 state Medicaid programs and included 1 966 689 Black and White Medicaid enrollees. Analyses were performed between January 28, 2021, and October 18, 2021. Exposures: Self-reported race. Main Outcomes and Measures: Rates and racial differences in health care spending and utilization (including Healthcare Effectiveness Data and Information Set [HEDIS] access measures). Results: Of 1 966 689 Medicaid adults and children (mean [SD] age, 20.3 [17.1] years; 1 119 136 [56.9%] female), 867 183 (44.1%) self-identified as non-Hispanic Black and 1 099 506 (55.9%) self-identified as non-Hispanic White. Results were adjusted for age, sex, Medicaid eligibility category, zip code, health status, and usual source of care. On average, annual spending on Black adult (19 years or older) Medicaid enrollees was $317 (95% CI, $259-$375) lower than White enrollees, a 6% difference. Among children (18 years or younger), annual spending on Black enrollees was $256 (14%) lower (95% CI, $222-$290). Adult Black enrollees also had 19.3 (95% CI, 16.78-21.84), or 4%, fewer primary care encounters per 100 enrollees per year compared with White enrollees. Among children, the differences in primary care utilization were larger: Black enrollees had 90.1 (95% CI, 88.2-91.8) fewer primary care encounters per 100 enrollees per year compared with White enrollees, a 23% difference. Black enrollees had lower utilization of most other services, including high-value prescription drugs, but higher emergency department use and rates of HEDIS preventive screenings. Conclusions and Relevance: In this cross-sectional study of US Medicaid enrollees in 3 states, Black enrollees generated lower spending and used fewer services, including primary care and recommended care for acute and chronic conditions, but had substantially higher emergency department use. While Black enrollees had higher rates of HEDIS preventive screenings, ensuring equitable access to all services in Medicaid must remain a national priority.

Racial/Ethnic Disparities in Substance Use Treatment in Medicaid Managed Care in New York City: The Role of Plan and Geography.

OBJECTIVE: The aim was to assess the magnitude of health care disparities in treatment for substance use disorder (SUD) and the role of health plan membership and place of residence in observed disparities in Medicaid Managed Care (MMC) plans in New York City (NYC). DATA SOURCE: Medicaid claims and managed care plan enrollment files for 2015-2017 in NYC. RESEARCH DESIGN: We studied Medicaid enrollees with a SUD diagnosis during their first 6 months of enrollment in a managed care plan in 2015-2017. A series of linear regression models quantified service disparities across race/ethnicity for 5 outcome indicators: treatment engagement, receipt of psychosocial treatment, follow-up after withdrawal, rapid readmission, and treatment continuation. We assessed the degree to which plan membership and place of residence contributed to observed disparities. RESULTS: We found disparities in access to treatment but the magnitude of the disparities in most cases was small. Plan membership and geography of residence explained little of the observed disparities. One exception is geography of residence among Asian Americans, which appears to mediate disparities for 2 of our 5 outcome measures. CONCLUSIONS: Reallocating enrollees among MMC plans in NYC or evolving trends in group place of residence are unlikely to reduce disparities in treatment for SUD. System-wide reforms are needed to mitigate disparities.

In Medicaid Managed Care Networks, Care Is Highly Concentrated Among A Small Percentage Of Physicians.

States have increasingly outsourced the provision of Medicaid services to private managed care plans. To ensure that plans maintain access to care, many states set network adequacy standards that require plans to contract with a minimum number of physicians. In this study we used data from the period 2015-17 for four states to assess the level of Medicaid participation among physicians listed in the provider network directories of each managed care plan. We found that about one-third of outpatient primary care and specialist physicians contracted with Medicaid managed care plans in our sample saw fewer than ten Medicaid beneficiaries in a year. Care was highly concentrated: 25 percent of primary care physicians provided 86 percent of the care, and 25 percent of specialists, on average, provided 75 percent of the care. Our findings suggest that current network adequacy standards might not reflect actual access; new methods are needed that account for beneficiaries' preferences and physicians' willingness to serve Medicaid patients.

Residual Confounding in Health Plan Performance Assessments: Evidence From Randomization in Medicaid.

BACKGROUND: Risk adjustment is used widely in payment systems and performance assessments, but the extent to which it distinguishes plan or provider effects from confounding due to patient differences is typically unknown. OBJECTIVE: To assess the degree to which risk-adjusted measures of health plan performance adequately adjust for the variation across plans that arises because of differences in patient characteristics (residual confounding). DESIGN: Comparison between plan performance estimates based on enrollees who made plan choices (observational population) and estimates based on enrollees assigned to plans (randomized population). SETTING: Natural experiment in which more than two thirds of a state's Medicaid population in 1 region was randomly assigned to 1 of 5 plans. PARTICIPANTS: 137 933 enrollees in 2013 to 2014, of whom 31.1% selected a plan and 68.9% were randomly assigned to 1 of the same 5 plans. MEASUREMENTS: Annual total spending (that is, payments to providers), primary care use, dental care use, and avoidable emergency department visits, all scored as plan-specific deviations from the "average" plan performance within each population. RESULTS: Enrollee characteristics were appreciably imbalanced across plans in the observational population, as expected, but were not in the randomized population. Annual total spending varied across plans more in the observational population (SD, $147 per enrollee) than in the randomized population (SD, $70 per enrollee) after accounting for baseline differences in the observational and randomized populations and for differences across plans. On average, a plan's spending score (its deviation from the "average" performance) in the observational population differed from its score in the randomized population by $67 per enrollee in absolute value (95% CI, $38 to $123), or 4.2% of mean spending per enrollee (P = 0.009, rejecting the null hypothesis that this difference would be expected from sampling error). The difference was reduced modestly by risk adjustment to $62 per enrollee (P = 0.012). Residual confounding was similarly substantial for most other performance measures. Further adjustment for social factors did not materially change estimates. LIMITATION: Potential heterogeneity in plan effects between the 2 populations. CONCLUSION: Residual confounding in risk-adjusted performance assessments can be substantial and should caution policymakers against assuming that risk adjustment isolates real differences in plan performance. PRIMARY FUNDING SOURCE: Arnold Ventures.