Quality, Spending, Utilization, and Outcomes Among Dual-Eligible Medicare-Medicaid Beneficiaries in Integrated Care Programs: A Systematic Review.

Importance: Most dual-eligible Medicare-Medicaid beneficiaries are enrolled in bifurcated insurance programs that pay for different components of care. Therefore, policymakers are prioritizing expansion of integrated care plans (ICPs) that manage both Medicare and Medicaid benefits and spending. Objective: To review evidence of the association between ICPs and health care spending, quality, utilization, and patient outcomes among dual-eligible beneficiaries. Evidence Review: A search was conducted of PubMed/MEDLINE (January 1, 2010, through November 1, 2023) and Google Scholar (January 1, 2010, through October 1, 2023) and augmented with reports from US federal and state government websites. Three categories of ICPs were evaluated: Programs of All-Inclusive Care for the Elderly (PACE), Medicare-Medicaid Plans (MMPs), and Fully Integrated Dual Eligible Special Needs Plans (FIDE-SNPs) and related models aligning Medicare and Medicaid coverage. The review included studies that evaluated beneficiaries dually eligible for and enrolled in full Medicaid; compared an ICP to a nonintegrated arrangement; and evaluated utilization, spending, care coordination, patient experience, or health for 100 or more beneficiaries. Findings: In all, 26 ICP evaluations met the inclusion criteria and were included in the analysis: 5 of PACE, 13 of MMPs, and 8 of FIDE-SNPs and other aligned models. Evidence generally showed associated reductions in long-term nursing home stays in PACE (3 of 4 studies) and FIDE-SNPs and related aligned models (3 of 5 studies) but was mixed in evaluations of MMPs. Four of 9 studies of MMPs and 2 of 3 studies of FIDE-SNPs found higher outpatient use, although other studies showed no difference. Evidence on Medicaid spending was limited, whereas 8 of 10 studies of MMPs showed an association between these plans and higher Medicare spending. Evidence was mixed or inconclusive regarding care coordination and hospitalizations, and it was insufficient to evaluate patient satisfaction, health, and outcomes in beneficiary subgroups (eg, those with serious mental illness). Furthermore, studies had limited ability to control for bias from unmeasured differences between enrollees of ICPs compared with nonintegrated models. Conclusions and Relevance: This systematic review found variability and gaps in evidence regarding ICPs and spending, quality, utilization, and outcomes. Studies found some ICPs were associated with reductions in long-term nursing home admissions, and several identified increases in outpatient care. However, MMPs were primarily associated with higher Medicare spending. Evidence for other outcomes was limited or inconclusive. Research addressing these evidence gaps is needed to guide ongoing efforts to integrate coverage and care for dual-eligible beneficiaries.

No Association Between Medicare Advantage Providers' Network Restrictiveness and Star Rating Between 2013 and 2017: An Observational Study.

BACKGROUND: Medicare beneficiaries are increasingly enrolling in Medicare Advantage (MA), which employs a wide range of practices around restriction of the networks of providers that beneficiaries visit. Though Medicare beneficiaries highly value provider choice, it is unknown whether the MA contract quality metrics which beneficiaries use to inform their contract selection capture the restrictiveness of contracts' provider networks. OBJECTIVE: We evaluated whether there are meaningful associations between provider network restrictiveness (across primary care, psychiatry, and endocrinology providers) and contracts' overall star quality rating, as well as between network restrictiveness and contracts' performance on access to care measures from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey. PARTICIPANTS: Medicare Advantage contracts with health maintenance organization (HMO), local preferred provider organization (PPO), and point of service (POS) plans with available data. DESIGN: A cross-sectional analysis using multivariable linear regressions to assess the relationship between provider network restrictiveness and contract quality scores in 2013 through 2017. MEASURES: Statistical significance in the relationship between network restrictiveness and contract performance on quality measures. RESULTS: Across all study years, we included 562 unique contracts and 2801 contract-years. We find no evidence of consistent relationships between MA physician network restrictiveness and contract star rating. For primary care, psychiatry, and endocrinology, respectively, a 10 percentage point increase in restrictiveness was associated with a 0.02 (95% confidence interval [CI] -0.01 to 0.04), 0.0008 (95% CI, -0.01 to 0.02), and -0.01 (95% CI, -0.01 to 0.001) difference in star rating (p-value > 0.05 for all). Similarly, we find no evidence of consistent relationships between network restrictiveness and access to care measures. CONCLUSIONS: Our findings suggest that existing MA contract quality measures are not useful for indicating differences in network restrictiveness. Given the importance of provider choice to beneficiaries, more specific metrics may be needed to facilitate informed decisions about MA coverage.

Prevalence of Gender-Affirming Surgical Procedures Among Minors and Adults in the US.

This cross-sectional study uses a national dataset to examine the prevalence of gender-affirming surgical procedures among minors and adults in the US.

Coverage and Access Changes During Medicaid Unwinding.

Importance: States resumed Medicaid eligibility redeterminations, which had been paused during the COVID-19 public health emergency, in 2023. This unwinding of the pandemic continuous coverage provision raised concerns about the extent to which beneficiaries would lose Medicaid coverage and how that would affect access to care. Objective: To assess early changes in insurance and access to care during Medicaid unwinding among individuals with low incomes in 4 Southern states. Design, Setting, and Participants: This multimodal survey was conducted in Arkansas, Kentucky, Louisiana, and Texas from September to November 2023, used random-digit dialing and probabilistic address-based sampling, and included US citizens aged 19 to 64 years reporting 2022 incomes at or less than 138% of the federal poverty level. Exposure: Medicaid enrollment at any point since March 2020, when continuous coverage began. Main Outcomes and Measures: Self-reported disenrollment from Medicaid, insurance at the time of interview, and self-reported access to care. Using multivariate logistic regression, factors associated with Medicaid loss were evaluated. Access and affordability of care among respondents who exited Medicaid vs those who remained enrolled were compared, after multivariate adjustment. Results: The sample contained 2210 adults (1282 women [58.0%]; 505 Black non-Hispanic individuals [22.9%], 393 Hispanic individuals [17.8%], and 1133 White non-Hispanic individuals [51.3%]) with 2022 household incomes less than 138% of the federal poverty line. On a survey-weighted basis, 1564 (70.8%) reported that they and/or a dependent child of theirs had Medicaid at some point since March 2020. Among adult respondents who had Medicaid, 179 (12.5%) were no longer enrolled in Medicaid at the time of the survey, with state estimates ranging from 7.0% (n = 19) in Kentucky to 16.2% (n = 82) in Arkansas. Fewer children who had Medicaid lost coverage (42 [5.4%]). Among adult respondents who left Medicaid since 2020 and reported coverage status at time of interview, 47.8% (n = 80) were uninsured, 27.0% (n = 45) had employer-sponsored insurance, and the remainder had other coverage as of fall 2023. Disenrollment was higher among younger adults, employed individuals, and rural residents but lower among non-Hispanic Black respondents (compared with non-Hispanic White respondents) and among those receiving Supplemental Nutrition Assistance Program benefits. Losing Medicaid was significantly associated with delaying care due to cost and worsening affordability of care. Conclusions and Relevance: The results of this survey study indicated that 6 months into unwinding, 1 in 8 Medicaid beneficiaries reported exiting the program, with wide state variation. Roughly half who lost Medicaid coverage became uninsured. Among those moving to new coverage, many experienced coverage gaps. Adults exiting Medicaid reported more challenges accessing care than respondents who remained enrolled.

Antiretroviral Therapy Use and Disparities Among Medicare Beneficiaries with HIV.

BACKGROUND: Antiretroviral therapy (ART) is recommended for all people with HIV. Understanding ART use among Medicare beneficiaries with HIV is therefore critically important for improving quality and equity of care among the growing population of older adults with HIV. However, a comprehensive national evaluation of filled ART prescriptions among Medicare beneficiaries is lacking. OBJECTIVE: To examine trends in ART use among Medicare beneficiaries with HIV from 2013 to 2019 and to evaluate whether racial and ethnic disparities in ART use are narrowing over time. DESIGN: Retrospective observational study. SUBJECTS: Traditional Medicare beneficiaries with Part D living with HIV in 2013-2019. MAIN MEASURES: Months of filled ART prescriptions each year. KEY RESULTS: Compared with beneficiaries not on ART, beneficiaries on ART were younger, less likely to be Black (41.6% vs. 47.0%), and more likely to be Hispanic (13.1% vs. 9.7%). While the share of beneficiaries who filled ART prescriptions for 10 + months/year improved (+ 0.48 percentage points/year [p.p.y.], 95% CI 0.34-0.63, p < 0.001), 25.8% of beneficiaries did not fill ART for 10 + months in 2019. Between 2013 and 2019, the proportion of beneficiaries who filled ART for 10 + months improved for Black beneficiaries (65.8 to 70.3%, + 0.66 p.p.y., 95% CI 0.43-0.89, p < 0.001) and White beneficiaries (74.8 to 77.4%, + 0.38 p.p.y.; 95% CI 0.19-0.58, p < 0.001), while remaining stable for Hispanic beneficiaries (74.5 to 75.0%, + 0.12 p.p.y., 95% CI - 0.24-0.49, p = 0.51). Although Black-White disparities in ART use narrowed over time, the share of beneficiaries who filled ART prescriptions for 10 + months/year was significantly lower among Black beneficiaries relative to White beneficiaries each year. CONCLUSIONS: ART use improved from 2013 to 2019 among Medicare beneficiaries with HIV. However, about 25% of beneficiaries did not consistently fill ART prescriptions within a given year. Despite declining differences between Black and White beneficiaries, concerning disparities in ART use persist.

NFixDB (Nitrogen Fixation DataBase)-a comprehensive integrated database for robust 'omics analysis of diazotrophs.

Biological nitrogen fixation is a fundamental biogeochemical process that transforms molecular nitrogen into biologically available nitrogen via diazotrophic microbes. Diazotrophs anaerobically fix nitrogen using the nitrogenase enzyme which is arranged in three different gene clusters: (i) molybdenum nitrogenase (nifHDK) is the most abundant, followed by it's alternatives, (ii) vanadium nitrogenase (vnfHDK) and (iii) iron nitrogenase (anfHDK). Multiple databases have been constructed as resources for diazotrophic 'omics analysis; however, an integrated database based on whole genome references does not exist. Here, we present NFixDB (Nitrogen Fixation DataBase), a comprehensive integrated whole genome based database for diazotrophs, which includes all nitrogenases (nifHDK, vnfHDK, anfHDK) and nitrogenase-like enzymes (e.g. nflHD) linked to ribosomal RNA operons (16S-5S-23S). NFixDB was computed using Hidden Markov Models (HMMs) against the entire whole genome based Genome Taxonomy Database (GTDB R214), providing searchable reference HMMs for all nitrogenase and nitrogenase-like genes, complete ribosomal RNA operons, both GTDB and NCBI/RefSeq taxonomy, and an SQL database for querying matches. We compared NFixDB to nifH databases from Buckley, Zehr, Mise and FunGene finding extensive evidence of nifH, in addition to vnfH and nflH. NFixDB contains >4000 verified nifHDK sequences contained on 50 unique phyla of bacteria and archaea. NFixDB provides the first comprehensive nitrogenase database available to researchers unlocking diazotrophic microbial potential.

Functional studies of plant transcription factors and their relevance in the plant root-knot nematode interaction.

Root-knot nematodes are polyphagous parasitic nematodes that cause severe losses in the agriculture worldwide. They enter the root in the elongation zone and subtly migrate to the root meristem where they reach the vascular cylinder and establish a feeding site called gall. Inside the galls they induce a group of transfer cells that serve to nurture them along their parasitic stage, the giant cells. Galls and giant cells develop through a process of post-embryogenic organogenesis that involves manipulating different genetic regulatory networks within the cells, some of them through hijacking some molecular transducers of established plant developmental processes, such as lateral root formation or root regeneration. Galls/giant cells formation involves different mechanisms orchestrated by the nematode´s effectors that generate diverse plant responses in different plant tissues, some of them include sophisticated mechanisms to overcome plant defenses. Yet, the plant-nematode interaction is normally accompanied to dramatic transcriptomic changes within the galls and giant cells. It is therefore expected a key regulatory role of plant-transcription factors, coordinating both, the new organogenesis process induced by the RKNs and the plant response against the nematode. Knowing the role of plant-transcription factors participating in this process becomes essential for a clear understanding of the plant-RKNs interaction and provides an opportunity for the future development and design of directed control strategies. In this review, we present the existing knowledge of the TFs with a functional role in the plant-RKN interaction through a comprehensive analysis of current scientific literature and available transcriptomic data.

The microtubule targeting agent ST-401 triggers cell death in interphase and prevents the formation of polyploid giant cancer cells.

Microtubule targeting agents (MTAs) are commonly prescribed to treat cancers and predominantly kill cancer cells in mitosis. Significantly, some MTA-treated cancer cells escape death in mitosis, exit mitosis and become malignant polyploid giant cancer cells (PGCC). Considering the low number of cancer cells undergoing mitosis in tumor tissues, killing them in interphase may represent a favored antitumor approach. We discovered that ST-401, a mild inhibitor of microtubule (MT) assembly, preferentially kills cancer cells in interphase as opposed to mitosis, a cell death mechanism that avoids the development of PGCC. Single cell RNA sequencing identified mRNA transcripts regulated by ST-401, including mRNAs involved in ribosome and mitochondrial functions. Accordingly, ST-401 induces a transient integrated stress response, reduces energy metabolism, and promotes mitochondria fission. This cell response may underly death in interphase and avoid the development of PGCC. Considering that ST-401 is a brain-penetrant MTA, we validated these results in glioblastoma cell lines and found that ST-401 also reduces energy metabolism and promotes mitochondria fission in GBM sensitive lines. Thus, brain-penetrant mild inhibitors of MT assembly, such as ST-401, that induce death in interphase through a previously unanticipated antitumor mechanism represent a potentially transformative new class of therapeutics for the treatment of GBM.

MerCat2: a versatile k-mer counter and diversity estimator for database-independent property analysis obtained from omics data.

Motivation: MerCat2 ("Mer-Catenate2") is a versatile, parallel, scalable and modular property software package for robustly analyzing features in omics data. Using massively parallel sequencing raw reads, assembled contigs, and protein sequences from any platform as input, MerCat2 performs k-mer counting of any length k, resulting in feature abundance counts tables, quality control reports, protein feature metrics, and graphical representation (i.e. principal component analysis (PCA)). Results: MerCat2 allows for direct analysis of data properties in a database-independent manner that initializes all data, which other profilers and assembly-based methods cannot perform. MerCat2 represents an integrated tool to illuminate omics data within a sample for rapid cross-examination and comparisons. Availability and implementation: MerCat2 is written in Python and distributed under a BSD-3 license. The source code of MerCat2 is freely available at https://github.com/raw-lab/mercat2. MerCat2 is compatible with Python 3 on Mac OS X and Linux. MerCat2 can also be easily installed using bioconda: mamba create -n mercat2 -c conda-forge -c bioconda mercat2.

A surge in food insecurity during the COVID-19 pandemic in a cohort in Mexico City.

BACKGROUND: The COVID-19 pandemic has not only caused tremendous loss of life and health but has also greatly disrupted the world economy. The impact of this disruption has been especially harsh in urban settings of developing countries. We estimated the impact of the pandemic on the occurrence of food insecurity in a cohort of women living in Mexico City, and the socioeconomic characteristics associated with food insecurity severity. METHODS: We analyzed data longitudinally from 685 women in the Mexico City-based ELEMENT cohort. Food insecurity at the household level was gathered using the Latin American and Caribbean Food Security Scale and measured in-person during 2015 to 2019 before the pandemic and by telephone during 2020-2021, in the midst of the pandemic. Fluctuations in the average of food insecurity as a function of calendar time were modeled using kernel-weighted local polynomial regression. Fixed and random-effects ordinal logistic regression models of food insecurity were fitted, with timing of data collection (pre-pandemic vs. during pandemic) as the main predictor. RESULTS: Food insecurity (at any level) increased from 41.6% during the pre-pandemic period to 53.8% in the pandemic stage. This increase was higher in the combined severe-moderate food insecurity levels: from 1.6% pre-pandemic to 16.8% during the pandemic. The odds of severe food insecurity were 3.4 times higher during the pandemic relative to pre-pandemic levels (p<0.01). Socioeconomic status quintile (Q) was significantly related to food insecurity (Q2 OR = 0.35 p<0.1, Q3 OR = 0.48 p = 0.014, Q4 OR = 0.24 p<0.01, and Q5 OR = 0.17 p<0.01), as well as lack of access to social security (OR = 1.69, p = 0.01), and schooling (OR = 0.37, p<0.01). CONCLUSIONS: Food insecurity increased in Mexico City households in the ELEMENT cohort as a result of the COVID-19 pandemic. These results contribute to the body of evidence suggesting that governments should implement well-designed, focalized programs in the context of economic crisis such as the one caused by COVID-19 to prevent families from the expected adverse health and well-being consequences associated to food insecurity, especially for the most vulnerable.

Restrictiveness of Medicare Advantage provider networks across physician specialties.

OBJECTIVE: The objective was to measure specialty provider networks in Medicare Advantage (MA) and examine associations with market factors. DATA SOURCES AND STUDY SETTING: We relied on traditional Medicare (TM) and MA prescription drug event data from 2011 to 2017 for all Medicare beneficiaries in the United States as well as data from the Area Health Resources File. STUDY DESIGN: Relying on a recently developed and validated prediction model, we calculated the provider network restrictiveness of MA contracts for nine high-prescribing specialties. We characterized network restrictiveness through an observed-to-expected ratio, calculated as the number of unique providers seen by MA beneficiaries divided by the number expected based on the prediction model. We assessed the relationship between network restrictiveness and market factors across specialties with multivariable linear regression. DATA COLLECTION/EXTRACTION METHODS: Prescription drug event data for a 20% random sample of beneficiaries enrolled in prescription drug coverage from 2011 to 2017. PRINCIPAL FINDINGS: Provider networks in MA varied in restrictiveness. OB-Gynecology was the most restrictive with enrollees seeing 34.5% (95% CI: 34.3%-34.7%) as many providers as they would absent network restrictions; cardiology was the least restrictive with enrollees seeing 58.6% (95% CI: 58.4%-58.8%) as many providers as they otherwise would. Factors associated with less restrictive networks included the county-level TM average hierarchical condition category score (0.06; 95% CI: 0.04-0.07), the county-level number of doctors per 1000 population (0.04; 95% CI: 0.02-0.05), the natural log of local median household income (0.03; 95% CI: 0.007-0.05), and the parent company's market share in the county (0.16; 95% CI: 0.13-0.18). Rurality was a major predictor of more restrictive networks (-0.28; 95% CI: -0.32 to -0.24). CONCLUSIONS: Our findings suggest that rural beneficiaries may face disproportionately reduced access in these networks and that efforts to improve access should vary by specialty.

Medicaid Eligibility Loss Among Dual-Eligible Beneficiaries Before and During COVID-19 Public Health Emergency.

Importance: Medicaid coverage loss can substantially compromise access to and affordability of health care for dual-eligible beneficiaries. The extent to which this population lost Medicaid coverage before and during the COVID-19 public health emergency (PHE) and the characteristics of beneficiaries more at risk for coverage loss are currently not well known. Objective: To assess the loss of Medicaid coverage among dual-eligible beneficiaries before and during the first year of the PHE, and to examine beneficiary-level and plan-level factors associated with heightened likelihood of losing Medicaid. Design, Setting, and Participants: This repeated cross-sectional study used national Medicare data to estimate annual rates of Medicaid loss among dual-eligible beneficiaries before (2015 to 2019) and during the PHE (2020). Individuals who were dual eligible for Medicare and Medicaid at the beginning of a given year and who continuously received low-income subsidies for Medicare Part D prescription drug coverage were included in the sample. Multivariable regression models were used to examine beneficiary-level and plan-level factors associated with Medicaid loss. Data analyses were conducted between March 2023 and October 2023. Exposure: Onset of PHE. Main Outcomes and Measures: Loss of Medicaid for at least 1 month within a year. Results: Sample included 56 172 736 dual-eligible beneficiary-years between 2015 and 2020. In 2020, most dual-eligible beneficiaries were aged over 65 years (5 984 420 [61.1%]), female (5 868 866 [59.9%]), non-Hispanic White (4 928 035 [50.3%]), full-benefit eligible (6 837 815 [69.8%]), and enrolled in traditional Medicare (5 343 537 [54.6%]). The adjusted proportion of dual-eligible beneficiaries losing Medicaid for at least 1 month increased from 6.6% in 2015 to 7.3% in 2019 and then dropped to 2.3% in 2020. Between 2015 and 2019, dual-eligible beneficiaries who were older (ages 55-64 years: -1.4%; 95% CI, -1.8% to -1.0%; ages 65-74 years: -2.0%; 95% CI, -2.5% to -1.5%; ages 75 and older: -4.5%; 95% CI, -5.0% to -4.0%), disabled (-0.8%; 95% CI, -1.1% to -0.6%), and in integrated care programs were less likely to lose Medicaid. In 2020, the disparities within each of these demographic groups narrowed significantly. Notably, while Black (0.6%; 95% CI, 0.2% to 0.9%) and Hispanic (0.7%; 95% CI, 0.3% to 1.2%) dual-eligible beneficiaries were more likely to lose Medicaid than their non-Hispanic White counterparts between 2015 and 2019, such gap was eliminated for Black beneficiaries and narrowed for Hispanic beneficiaries in 2020. Conclusions and Relevance: During the PHE, Medicaid coverage loss declined significantly among dual-eligible beneficiaries, and disparities were mitigated across subgroups. As the PHE unwinds, it is crucial for policymakers to implement strategies to minimize Medicaid coverage disruptions and racial and ethnic disparities, especially given that loss of Medicaid was slightly increasing over time before the PHE.

Disparities in Access to Outpatient Surgery Related to Removal of Procedures from Medicare's Inpatient Only List.

OBJECTIVE: We assessed the shift from inpatient to outpatient surgical care related to changes to the Inpatient Only List in 2020 and 2021 compared to 2019. SUMMARY BACKGROUND DATA: The extent to which procedures shift from the inpatient to outpatient setting following removal from Medicare's Inpatient Only List is unknown. Many health systems also encouraged a shift from inpatient to outpatient surgery during the COVID-19 pandemic. Assessing the relative change in outpatient surgical utilization for procedures removed from the Inpatient Only List during COVID-19 would provide empirical data on whether reimbursement policy changes or inpatient capacity needs during the pandemic were more likely to shift care from the inpatient to outpatient setting. METHODS: We used administrative data from the PINC AI Healthcare Database across 723 hospitals to determine the within-facility relative change in outpatient vs inpatient procedural volume in 2020 and 2021 compared to 2019 using a multivariable conditional fixed-effects Poisson regression model. We also assessed whether outpatient surgical utilization varied by race and ethnicity. Using a multivariable linear probability model, we assessed the absolute change in risk-adjusted 30-day complication, readmission, and mortality rates for inpatient and outpatient surgical procedures. RESULTS: In 2020 and 2021 compared to 2019 respectively, there was a 5.3% (95% CI, 1.4% to 9.5%) and 41.3% (95% CI 33.1% to 50.0%) relative increase in outpatient elective procedural volume. Outpatient procedural volume increased most significantly for hip replacement which was removed from the Inpatient Only List in 2020 (increase in outpatient surgical utilization of 589.3% (95% CI, 524.9% to 660.3%)). The shift to outpatient hip replacement procedures was concentrated among White patients; in 2021, hip replacement procedural volume increased by 271.1% (95% CI, 241.2% and 303.7%) for White patients and 29.5% (95% CI, 24.4% and 34.9%) for Black patients compared to 2019 levels. There were no consistent or large changes in 30-day complication, readmission, or mortality risk in 2020 and 2021 compared to 2019. CONCLUSION: There was a modest increase in elective outpatient surgeries and a pronounced increase in outpatient orthopedic surgeries which were removed from the Inpatient Only List during the COVID-19 pandemic. Utilization of outpatient surgical procedures was concentrated among White patients.

A heterogeneous pharmaco-transcriptomic landscape induced by targeting a single oncogenic kinase.

Over-activation of the epidermal growth factor receptor (EGFR) is a hallmark of glioblastoma. However, EGFR-targeted therapies have led to minimal clinical response. While delivery of EGFR inhibitors (EGFRis) to the brain constitutes a major challenge, how additional drug-specific features alter efficacy remains poorly understood. We apply highly multiplex single-cell chemical genomics to define the molecular response of glioblastoma to EGFRis. Using a deep generative framework, we identify shared and drug-specific transcriptional programs that group EGFRis into distinct molecular classes. We identify programs that differ by the chemical properties of EGFRis, including induction of adaptive transcription and modulation of immunogenic gene expression. Finally, we demonstrate that pro-immunogenic expression changes associated with a subset of tyrphostin family EGFRis increase the ability of T-cells to target glioblastoma cells.

Institutional Efforts to Address Legacies of Slavery-Implications for the Health Care System.

This JAMA Forum discusses the legacies of slavery, efforts underway at colleges and universities to explore and address the legacies of slavery, and health care system actions to address structural racism.

Trends in observation stays for Medicare beneficiaries with and without Alzheimer's disease and related dementias.

BACKGROUND: There has been a marked rise in the use of observation care for Medicare beneficiaries visiting the emergency department (ED) in recent years. Whether trends in observation use differ for people with Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) is unknown. METHODS: Using a national 20% sample of Medicare beneficiaries ages 68+ from 2012 to 2018, we compared trends in ED visits and observation stays by AD/ADRD status for beneficiaries visiting the ED. We then examined the degree to which trends differed by nursing home (NH) residency status, assigning beneficiaries to four groups: AD/ADRD residing in NH (AD/ADRD+ NH+), AD/ADRD not residing in NH (AD/ADRD+ NH-), no AD/ADRD residing in NH (AD/ADRD- NH+), and no AD/ADRD not residing in NH (AD/ADRD- NH-). RESULTS: Of 7,489,780 unique beneficiaries, 18.6% had an AD/ADRD diagnosis. Beneficiaries with AD/ADRD had more than double the number of ED visits per 1000 in all years compared to those without AD/ADRD and saw a faster adjusted increase over time (+26.7 vs. +8.2 visits/year; p < 0.001 for interaction). The annual increase in the adjusted proportion of ED visits ending in observation was also greater among people with AD/ADRD (+0.78%/year, 95% CI 0.77-0.80%) compared to those without AD/ADRD (+0.63%/year, 95% CI 0.59-0.66%; p < 0.001 for interaction). Observation utilization was greatest for the AD/ADRD+ NH+ population and lowest for the AD/ADRD- NH- population, but the AD/ADRD+ NH- group saw the greatest increase in observation stays over time (+15.4 stays per 1000 people per year, 95% CI 15.0-15.7). CONCLUSIONS: Medicare beneficiaries with AD/ADRD have seen a disproportionate increase in observation utilization in recent years, driven by both an increase in ED visits and an increase in the proportion of ED visits ending in observation.

The Rise and Risks of Medicare Advantage "Affinity Plans".

This Viewpoint discusses the proliferation of Medicare Advantage plans targeting specific groups of individuals and whether these plans will improve quality of care for beneficiaries.

Starfysh integrates spatial transcriptomic and histologic data to reveal heterogeneous tumor-immune hubs.

Spatially resolved gene expression profiling provides insight into tissue organization and cell-cell crosstalk; however, sequencing-based spatial transcriptomics (ST) lacks single-cell resolution. Current ST analysis methods require single-cell RNA sequencing data as a reference for rigorous interpretation of cell states, mostly do not use associated histology images and are not capable of inferring shared neighborhoods across multiple tissues. Here we present Starfysh, a computational toolbox using a deep generative model that incorporates archetypal analysis and any known cell type markers to characterize known or new tissue-specific cell states without a single-cell reference. Starfysh improves the characterization of spatial dynamics in complex tissues using histology images and enables the comparison of niches as spatial hubs across tissues. Integrative analysis of primary estrogen receptor (ER)-positive breast cancer, triple-negative breast cancer (TNBC) and metaplastic breast cancer (MBC) tissues led to the identification of spatial hubs with patient- and disease-specific cell type compositions and revealed metabolic reprogramming shaping immunosuppressive hubs in aggressive MBC.

Multiplex single-cell chemical genomics reveals the kinase dependence of the response to targeted therapy.

Chemical genetic screens are a powerful tool for exploring how cancer cells' response to drugs is shaped by their mutations, yet they lack a molecular view of the contribution of individual genes to the response to exposure. Here, we present sci-Plex-Gene-by-Environment (sci-Plex-GxE), a platform for combined single-cell genetic and chemical screening at scale. We highlight the advantages of large-scale, unbiased screening by defining the contribution of each of 522 human kinases to the response of glioblastoma to different drugs designed to abrogate signaling from the receptor tyrosine kinase pathway. In total, we probed 14,121 gene-by-environment combinations across 1,052,205 single-cell transcriptomes. We identify an expression signature characteristic of compensatory adaptive signaling regulated in a MEK/MAPK-dependent manner. Further analyses aimed at preventing adaptation revealed promising combination therapies, including dual MEK and CDC7/CDK9 or nuclear factor κB (NF-κB) inhibitors, as potent means of preventing transcriptional adaptation of glioblastoma to targeted therapy.

Contribución de diversas fuentes de exposición a la concentración de plomo en sangre en población infantil mexicana, Ensanut 2022.

OBJETIVO: Analizar la asociación entre fuentes de exposición al plomo (FEPb) y la concentración en sangre capilar (PbS) en menores de 1 a 4 años de edad a nivel nacional y regional, así como cuantificar la contribución relativa de las distintas FEPb. Material y métodos. Se utilizaron datos de la Encuesta Nacional de Salud y Nutrición (Ensanut 2022). Las FEPb consideradas fueron uso de loza de barro vidriada con plomo (LBVPb), residencia cercana a sitios contaminados y exposición paraocupacional. Se estimaron prevalencias de intoxicación (PbS ≥ 5.0 mg/dL) y medias geométricas de PbS. Se utilizaron modelos de regresión para PbS (escala logarítmica) y la descomposición Shapley-Owen de R2 para evaluar la contribución relativa de cada FEPb. RESULTADOS: Las FEPb estudiadas explican el 6% de la variabilidad de PbS a nivel nacional; de este, el 87.3% lo explica el uso de LBVPb, el 4.2% otras FEPb ambiental y 1.3% FEPb paraocupacionales. La contribución relativa del uso de LBVPb varía entre regiones, desde 38.1 a 76.8%. Algunas regiones destacan la FEPb ambiental, pero no paraocupacional. CONCLUSIONES: Los resultados confirman que el uso de LBVPb es la principal fuente de exposición reportada y sugieren que la población no identifica las principales FEPb documentadas hasta ahora.