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Recent policies have restricted the rights of the US transgender people; there is a need to explore transgender people’s knowledge and attitudes regarding such policies and related mental health. In 2019, 580 transgender adults living in the Northeastern US completed a survey assessing demographics, knowledge/attitudes toward transgender-related policies, and mental health. Multivariable logistic regression models, adjusted for age, gender, race, and prior abuse, were fit to examine the association of concerns about the implementation of discriminatory policies and depression, anxiety, and post-traumatic stress disorder (PTSD). Many participants were confused about the status of federal and state protections for transgender people, and 48.4% were concerned that their state would pass policies that took away transgender rights. In adjusted models, compared to participants who were not concerned, those who were concerned about the enactment of state-level, anti-transgender policies had greater odds of depression, anxiety, and PTSD (p

BACKGROUND: Antiretroviral therapies (ART) are essential HIV care. As people living with HIV age and their presence in nursing homes (NH) increases, it is critical to evaluate the quality of HIV care. We determine the rate of ART use and examine individual and facility level characteristics associated with no ART use in a nationally representative long-stay NH residents with HIV. METHODS: This retrospective cohort study included all long-stay Medicare fee-for-service NH residents (2013–2016) with HIV who had a valid Minimum Data Set assessment. Residents were followed from long-stay qualification until death, Part D disenrollment, transfer from long-term care to another healthcare setting, or 12/31/2016. We identified individual and facility characteristics that associated with non-use of ART using generalized estimating equation logistic regression. RESULTS: 4,171 eligible HIV+ residents from 2,459 NHs were included in our study. Only 36% (1507/4171) received any ART regimen during an average of 11.6 months of observation. Older age, females, white race, receipt of Medicare skilled nursing benefits and some major cardiometabolic comorbidities and mental health conditions were associated with non-ART use. Rates of non-ART use did not vary significantly by residents’ end-of-life status (p=0.21). Residents in facilities with a higher HIV concentration [adjusted odds ratio (adjOR) 3.42; 95% confidence interval (CI) 2.13 – 5.48] and an AIDS unit (adjOR 2.51; 95% CI 1.92 – 3.30) had higher odds of using an ART. CONCLUSIONS AND IMPLICATIONS: The rate of ART use by HIV+ long-stay NH residents was low. Facilities’ experience with HIV played an important role in ART receipt. Interventions to improve rates of ART us in NHs are urgently needed to ensure optimal health outcomes.

Supplementary Figure 5 from Inhibition of the Acetyltransferases p300 and CBP Reveals a Targetable Function for p300 in the Survival and Invasion Pathways of Prostate Cancer Cell Lines

Supplementary Figure 3 from Inhibition of the Acetyltransferases p300 and CBP Reveals a Targetable Function for p300 in the Survival and Invasion Pathways of Prostate Cancer Cell Lines

Supplementary Figure 2 from Inhibition of the Acetyltransferases p300 and CBP Reveals a Targetable Function for p300 in the Survival and Invasion Pathways of Prostate Cancer Cell Lines

Supplementary Figure 4 from Inhibition of the Acetyltransferases p300 and CBP Reveals a Targetable Function for p300 in the Survival and Invasion Pathways of Prostate Cancer Cell Lines

Supplementary Table Legends 1-5 from Inhibition of the Acetyltransferases p300 and CBP Reveals a Targetable Function for p300 in the Survival and Invasion Pathways of Prostate Cancer Cell Lines

Histone modifications, largely regulated by histone acetyltransferases (HAT) and histone deacetylases, have been recognized as major regulatory mechanisms governing human diseases, including cancer. Despite significant effort and recent advances, the mechanism by which the HAT and transcriptional coactivator p300 mediates tumorigenesis remains unclear. Here, we use a genetic and chemical approach to identify the microphthalmia-associated transcription factor (MITF) as a critical downstream target of p300 driving human melanoma growth. Direct transcriptional control of MITF by p300-dependent histone acetylation within proximal gene regulatory regions was coupled to cellular proliferation, suggesting a significant growth regulatory axis. Further analysis revealed forkhead box M1 (FOXM1) as a key effector of the p300–MITF axis driving cell growth that is selectively activated in human melanomas. Targeted chemical inhibition of p300 acetyltransferase activity using a potent and selective catalytic p300/CBP inhibitor demonstrated significant growth inhibitory effects in melanoma cells expressing high levels of MITF. Collectively, these data confirm the critical role of the p300–MITF–FOXM1 axis in melanoma and support p300 as a promising novel epigenetic therapeutic target in human melanoma.Significance:These results show that MITF is a major downstream target of p300 in human melanoma whose expression is predictive of melanoma response to small-molecule inhibition of p300 HAT activity.

Figures S1-S5 and Table S1. Supplementary Figure S1. p300 depletion and phenotype analysis in melanoma cell lines. Supplementary Figure S2. Molecular pathways associated with p300 in melanoma. Supplementary Figure S3. MITF is essential for melanoma survival. Supplementary Figure S4. Characterization of p300/CBP HAT inhibitor A-485*. Supplementary Figure S5. Schematic procedure of A-485* synthesis. Table S1. ChIP�PCR primer sequences for the characterization of MITF gene upstream regulatory region

To understand differences in financial performance, quality performance, supplemental benefits provision, and enrollee composition between integrated and non-integrated plans in the Medicare Advantage (MA) program.We used data from the Center for Medicare and Medicaid Services for 2015-2017. We included 156 integrated MA plans (31 unique contracts) and 2096 non-integrated MA plans (392 unique contracts).We estimated linear probably models for financial performance, quality performance, supplemental benefits provision, and enrollee composition with state fixed effects and contract random effects. We adjusted for county-level market structure-related factors, cost-related factors, and demand-related factors. Our primary independent variable was an indicator of plan-provider integration.Integrated MA plans were associated with $19.4 (95% CI: 9.2, 29.7) and $16.6 (95% CI: 10.3, 22.9) higher Part C and Part D monthly premiums, but were associated with higher star quality ratings. There were no significant differences in revenues and plan payments per enrollee between integrated and non-integrated MA plans. Integrated MA plans were associated with $40.5 (95% CI: -54.0, -26.9) lower non-claims costs than non-integrated MA plans. There was limited evidence that integrated MA plans provided more generous supplemental benefits than non-integrated MA plans. Enrollment rates in integrated MA plans were particularly low among socially marginalized groups (3.4 [95% CI: -5.9, -1.0], 4.7 [95% CI: -8.5, -0.9], and 4.4 [95% CI: -6.4, -2.4] percentage points lower among non-Hispanic Black, Medicare-Medicaid dual eligible, and the disabled).Our findings suggest that integrated MA plans may achieve higher efficiency and quality, but these benefits may not be experienced by all beneficiaries due to disparities in enrollment. As these models continue to spread, it is critical to develop policies to ensure that MA enrollees have equal access to integrated plans.

Objectives The objective of this study was to examine racial/ethnic differences in enrollment trends for supplemental insurance coverage among traditional Medicare (TM) and Medicare Advantage (MA) beneficiaries. Study design We employed a retrospective cohort study design using the 2010-2016 Medicare Current Beneficiary Survey. Methods We included two types of outcomes: 1) seven exclusive types of insurance coverage in a given year and 2) changes in insurance coverage in the next year for those with each of the seven exclusive types of insurance coverage. Our primary independent variable was race/ethnicity. We conducted regression while controlling for demographic, socioeconomic, and health characteristics. We calculated the adjusted value of the outcome by race/ethnicity after adjusting for demographic, socioeconomic, and health status characteristics. Results We found substantial racial/ethnic differences in supplemental insurance coverage among TM and MA beneficiaries. Compared to White beneficiaries, racial/ethnic minority beneficiaries had lower adjusted rates of enrollment in Medigap among TM beneficiaries and higher enrollment in Medicaid among both TM and MA beneficiaries. Trends in enrollment differed by supplemental insurance coverage, but an increasing trend in enrollment among MA beneficiaries without supplemental insurance coverage and MA beneficiaries with Medicaid was notable. Overall trends were consistent across all racial/ethnic groups. Finally, most beneficiaries were less likely to change insurance coverage in the next year, but a distinct phenomenon was observed among Black beneficiaries with the lowest rates of remaining in Medigap or MA only. Conclusions Our findings indicate the minority Medicare beneficiaries may not have equitable access to supplemental insurance coverage.

This cross-sectional study assesses trends in the source of new enrollees to Medicare Advantage plans from 2012 to 2019.

Expansion of the Medicare Advantage program during 2009–18 saw greater enrollment among racial/ethnic minorities and other traditionally marginalized groups. Growth was more rapid among Black, Hisp...

BACKGROUND/OBJECTIVE Medicare Advantage (MA) and Accountable Care Organizations (ACOs) operate under incentives to reduce burdensome and costly care at the end of life. We compared end-of-life care for persons with dementia who are in MA, ACOs, or traditional Medicare (TM). DESIGN, SETTING, AND PARTICIPANTS Retrospective study of decedents with dementia enrolled in MA, attributed to an ACO, or in TM. Decedents had a nursing home stay between 91 and 180 days prior to death, two or more functional impairments, and mild to severe cognitive impairment. MEASUREMENTS Hospitalization, invasive mechanical ventilation (IMV) use, and in-hospital death in the last 30 days of life reported in Medicare billing. RESULTS Among 370,094 persons with dementia, 93,801 (25.4%) were in MA (mean age [SD], 86.9 [7.7], 67.6% female), 39,586 (10.7%) were ACO attributed (mean age [SD], 87.2 [7.6], 67.3% female), and 236,707 (63.9%) were in TM (mean age [SD], 87.0 [7.8], 67.6% female). The proportion hospitalized in the last 30 days of life was higher among TM enrollees (27.9%) and those ACO attributed (28.1%) than among MA enrollees (20.5%, p ≤ 0.001). After adjustment for socio-demographics, cognitive and functional impairments, comorbidities, and Hospital Referral Region, adjusted odds of hospitalization in the 30 days prior to death was 0.72 (95% confidence interval [CI] 0.70-0.74) among MA enrollees and 1.05 (95% CI 1.02-1.09) among those attributed to ACOs relative to TM enrollees. Relative to TM, the adjusted odds of death in the hospital were 0.78 (95% CI 0.75-0.81) among MA enrollees and 1.02 (95% CI 0.96-1.08) for ACO participants. Dementia decedents in MA had a lower likelihood of IMV use (adjusted odds ratio 0.80, 95% CI 0.75-0.85) compared to TM. CONCLUSIONS Among decedents with dementia, MA enrollees but not decedents in ACOs experienced less costly and potentially burdensome care compared with those with TM. Policy changes are needed for ACOs.

BACKGROUND: Medicare Advantage plans, private managed care plans that enrolled 34% of Medicare beneficiaries in 2019, received $6 billion in annual bonus payments on the basis of their performance on a 5-star rating system. Little is known, however, as to the extent these ratings adequately capture enrollee experience. OBJECTIVES: To measure the effect of exposure to higher rated Medicare Advantage contracts on enrollee experience. DESIGN: An instrumental variables analysis using MA contract consolidation as an exogenous shock to the quality of plan enrollees are exposed to. PARTICIPANTS: A total of 345,897 MA enrollees enrolled in non-consolidated contracts and 21,405 enrollees who were consolidated. MAIN MEASURES: The primary exposure was enrollee star rating, instrumented using contract consolidation. The primary outcomes were enrollee self-reported experience measures. KEY RESULTS: There were no significant effects on increased star ratings on 23 of 27 outcomes. A one-star increase in contract star rating leads to a 5.4 percentage point increase in reporting that pain does not interfere with daily activities (95%CI 2.4, 8.4), and a 4.4 percentage reduction in the likelihood that a physician would talk to the enrollee about physical activity (95%CI: −7.8, −1.1, all p

Medicare beneficiaries in rural areas may face challenges to gaining access to care, particularly if enrolled in Medicare Advantage (MA) plans with limited benefits and restrictive provider network...

Little is known about how well the Centers for Medicare and Medicaid Services' five-star rating system for the overall quality of Medicare Advantage (MA) contracts captures quality of care. Leveraging contract consolidation as a natural experiment to study the association between outcomes and insurer-initiated enrollee shifts to plans with higher-rated contracts, we found that enrollees experiencing a one-star MA rating increase were 20.8 percent less likely to voluntarily leave their plan to enroll in another plan or traditional Medicare. When hospitalized, they were 3.4 percent more likely to use a higher-quality hospital and 2.6 percent less likely to be readmitted within ninety days. Our findings suggest that MA star ratings may capture key domains of an MA plan's quality; however, the differences in outcomes that they capture might not all be clinically meaningful.

The non-invasive nature of NMR offers a means to monitor biochemical reactions in situ at the atomic-level. We harness this advantage to monitor a complex chemoenzymatic reaction that sequentially modifies reagents and loads the product on a nonribosomal peptide synthetase carrier protein. We present a protocol including a novel pulse sequence that permits to assess both the integrity of reagents and the completion of each step in the reaction, thus alleviating otherwise time-consuming and costly approaches to debug and repeat inefficient reactions. This study highlights the importance of NMR as a tool to establish reliable and reproducible experimental conditions in biochemical studies.Graphical Abstract

Background In the Medicare Advantage (MA) program, private plans receive capitated payments that are adjusted based on their enrollees' number and type of clinical conditions. Plans have the ability to review charts to identify additional conditions that are not present in claims data, thereby increasing risk-adjusted payments. Recently the Government Accountability Office released a report raising concerns about the use of these chart reviews as a potential tool for upcoding. Objectives To measure the extent to which plans receive additional payments for chart reviews, and the variation in chart reviews across plans. Research design In this cross-sectional study we use 2015 MA Encounter data to calculate how many additional diagnoses codes were added for each enrollee using chart reviews. We then calculate how these additional diagnosis codes translate to additional reimbursements across plans. Subjects A total of 14,021,692 beneficiaries enrolled in 510 MA contracts in 2015. Measures Individual and contract level hierarchical condition category codes, total plan reimbursement. Results Chart reviews were associated with a $2.3 billion increase in payments to plans, a 3.7% increase in Medicare spending to MA plans. Just 10% of plans accounted for 42% of the $2.3 billion in additional spending attributed to chart review. Among these plans, the relative increase in risk score from chart review was 17.2%. For-profit plans engaged in chart reviews substantially more frequently than nonprofit plans. Conclusions Given the substantial and highly variable increase in payments attributable to chart review, further investigation of the validity of this practice and its implications for Medicare spending is needed.

Health systems have increasingly developed integrated Medicare Advantage (MA) plans to align financial incentives and improve coordination of care and services across payer and provider. However, l...

BACKGROUND: The Medicare Advantage (MA) program is rapidly growing. Limited evidence exists about the care experiences of MA beneficiaries with Alzheimer's Disease and Related Dementia (ADRD). Our objective was to compare care experiences for MA beneficiaries with and without ADRD. METHODS: We examined MA beneficiaries who completed the Medicare Advantage Consumer Assessment of Healthcare Providers and Systems (CAHPS) and used inpatient, nursing home, or home health services in the past 3 years. We classified beneficiaries with ADRD using the presence of diagnosis codes in hospitals, nursing homes, and home health records. Our key measures included overall ratings of care and health plan, and indices of receiving timely care, care coordination, receiving needed care, and customer service. We compared differences between beneficiaries with and without ADRD using regression analysis adjusting for demographic, health, and plan characteristics, and stratifying by proxy response status. RESULTS: Among beneficiaries sampled by CAHPS, 22.2% with ADRD completed the survey compared to 38.5% without ADRD. Among proxy responses, beneficiaries with ADRD were 4.2 (95% CI: 0.1–8.4) percentage points less likely to report a high score for receiving needed care, and 3.5 percentage points (95% CI: 0.2–6.9) less likely to report a high score for customer service. Among non-proxy responses, those with ADRD were 9.0 (95% CI: 5.5–12.5) percentage points less likely to report a high score for needed care, and 8.5 (95% CI: 5.4–11.5) percentage points less likely to report a high score for customer service. CONCLUSIONS: ADRD respondents to the CAHPS were more likely to be excluded from CAHPS performance measures because they did not meet eligibility requirements and rates of non-response were higher. Among responders with or without a proxy, MA enrollees with an ADRD diagnosis reported worse care experiences in receiving needed care and in customer service than those without an ADRD diagnosis.

Health insurance literacy helps individuals make informed choices. However, evidence suggests that Medicare beneficiaries experience low health insurance literacy, leading to high-cost or poor-quality coverage choices.To examine how health insurance literacy was associated with coverage choices between traditional Medicare (TM) and Medicare Advantage (MA), as well as within MA.This cross-sectional study included 6627 TM and MA enrollees, using data from the 2015-2016 Medicare Current Beneficiary Survey. Data analyses were conducted between May 1 and June 30, 2021.Three self-reported measures of health insurance literacy (presence of information to make an informed comparison, ease in reviewing and comparing coverage options, and annual review and comparison of coverage options).Enrollment in TM vs MA and enrollment in an MA plan with different characteristics (star rating, monthly plan premium, in-network maximum out-of-pocket limit, plan type, and provision of supplemental benefits).We included 6627 Medicare beneficiaries (3578 women [54.0%]; mean [SD] age, 75.13 [7.12] years). A total of 77 individuals were Asian (1.2%), 696 were Black (10.5%), 488 were Hispanic (7.4%), 5277 were non-Hispanic White (79.6%), and 225 (3.4%) were single races not of Hispanic origin (including American Indian or Alaska Native and Native Hawaiian) or were 2 or more races. Medicare Advantage enrollment was higher among individuals with higher health insurance literacy than those with lower health insurance literacy, especially for those who reviewed or compared coverage options annually than among those who did not (38.0%; 95% CI, 36.0%-40.1% vs 27.8%; 95% CI, 25.8%-29.7%). Among MA beneficiaries, those who reviewed or compared coverage options annually were more likely to enroll in plans with 4 to 4.5 stars and plans with monthly premiums of $1 to $50 by 4.6 percentage points (95% CI, 0.1-9.2 percentage points) and 4.8 percentage points (95% CI, 0.6-9.0 percentage points), respectively. However, enrollment in plans with 5 stars was 3.8 percentage points lower (95% CI, -5.8 to -1.9 percentage points) among individuals who reviewed or compared coverage options annually than among those who did not. Among individuals with low socioeconomic status, the likelihood of reviewing or comparing coverage options annually was lower for those with Medicare and Medicaid dual eligibility than for those without it (odds ratio, 0.79; 95% CI, 0.63-0.99).Results of this study suggest that higher health insurance literacy-particularly, annual review and comparison of coverage choices-is associated with higher MA enrollment and choice of a particular MA plan. Policy makers should develop programs to encourage frequent review and comparison of coverage options for informed decision making.

ImportanceBefore 2021, most Medicare beneficiaries with end-stage renal disease (ESRD) were unable to enroll in private Medicare Advantage (MA) plans. The 21st Century Cures Act permitted these beneficiaries to enroll in MA plans effective January 2021.ObjectiveTo examine changes in MA enrollment among Medicare beneficiaries with ESRD after enactment of the 21st Century Cures Act overall and by race or ethnicity and dual-eligible status.Design, Setting, and ParticipantsThis cross-sectional time-trend study used data from Medicare beneficiaries with ESRD (both kidney transplant recipients and those undergoing dialysis) between January 2019 and December 2021. Data were analyzed between June and October 2022.Exposures21st Century Cures Act.Main Outcomes and MeasuresPrimary outcomes were the proportion of Medicare beneficiaries with prevalent ESRD who switched from traditional Medicare to MA between 2020 and 2021 and those with incident ESRD who newly enrolled in MA in 2021. Individuals who stayed in traditional Medicare were enrolled in 2020 and 2021 and those who switched to MA were enrolled in traditional Medicare in 2020 and MA in 2021.ResultsAmong 575 797 beneficiaries with ESRD in 2020 or 2021 (mean [SD] age, 64.7 [14.2] years, 42.2% female, 34.0% Black, and 7.7% Hispanic or Latino), the proportion of beneficiaries enrolled in MA increased from 24.8% (December 2020) to 37.4% (December 2021), a relative change of 50.8%. The largest relative increases in MA enrollment were among Black (72.8% relative increase), Hispanic (44.8%), and dual-eligible beneficiaries with ESRD (73.6%). Among 359 617 beneficiaries with TM and prevalent ESRD in 2020, 17.6% switched to MA in 2021. Compared with individuals who stayed in traditional Medicare, those who switched to MA had modestly more chronic conditions (6.3 vs 6.1; difference, 0.12 conditions [95% CI, 0.10-0.16]) and similar nondrug spending in 2020 (difference, $509 [95% CI, −$58 to $1075]) but were more likely to be Black (difference, 19.5 percentage points [95% CI, 19.1-19.9]) and have dual Medicare-Medicaid eligibility (difference, 20.8 percentage points [95% CI, 20.4-21.2]). Among beneficiaries who were newly eligible for Medicare ESRD benefits in 2021, 35.2% enrolled in MA.Conclusions and RelevanceResults suggest that increases in MA enrollment among Medicare beneficiaries with ESRD were substantial the first year after the 21st Century Cures Act, particularly among Black, Hispanic, and dual-eligible individuals. Policy makers and MA plans may need to assess network adequacy, disenrollment, and equity of care for beneficiaries who enrolled in MA.

Objectives To compare the use of top-ranked cancer hospitals for complex cancer surgery between Medicare Advantage (MA) and traditional Medicare fee-for-service (FFS) enrollees. Study design Cross-sectional analysis of Medicare claims and enrollment data. Methods The study used Medicare Provider Analysis and Review files to compare differences in use of top-ranked cancer hospitals for complex cancer surgery (lobectomy, esophagectomy, gastrectomy, colectomy, and the Whipple procedure [pancreaticoduodenectomy]) between MA and FFS enrollees 65 years and older who underwent the surgery in 2015 to 2017. Results After adjusting for demographic characteristics and county fixed effects, MA enrollees were less likely to use top-ranked cancer hospitals than FFS enrollees by 6.0 percentage points (95% CI, 4.7-7.2) overall; the difference varied from 3.5 percentage points (95% CI, 2.5-4.6) for colectomy to 14.3 percentage points (95% CI, 10.9-17.8) for the Whipple procedure. The difference in cancer surgery rate at a top-ranked cancer hospital between MA and FFS enrollees was larger for MA plans without out-of-network (OON) benefits (-7.5 percentage points; 95% CI, -9.1 to -5.9) than for MA plans with OON benefits (-2.3 percentage points; 95% CI, -2.9 to -1.7). Conclusions MA enrollees were less likely to use top-ranked cancer hospitals for complex cancer surgery than FFS enrollees. This difference was larger for MA plans with more restrictive OON policies. These findings suggest that MA enrollees, particularly those with lower OON benefits, may have restricted access to top-ranked hospitals for cancer care compared with FFS enrollees.

Although administrative claims data can be used to identify high-need (HN) Medicare beneficiaries, persistence in HN status among beneficiaries and subsequent variation in outcomes are unknown. We use national-level claims data to classify Fee-for-Service (FFS) Medicare beneficiaries as HN annually among beneficiaries continuously enrolled between 2013 and 2015. To examine persistence of HN status over time, we categorize longitudinal patterns in HN status into being never, newly, transiently, and persistently HN and examine differences in patients’ demographic characteristics and outcomes. Among survivors, 23% of beneficiaries were HN at any time—4% persistently HN, 13% transiently HN, and 6% newly HN. While beneficiaries who were persistently HN had higher mortality, utilization, and expenditures, classification as HN at any time was associated with poor outcomes. These findings demonstrate longitudinal variability of HN status among FFS beneficiaries and reveal the pervasiveness of poor outcomes associated with even transitory HN status over time.

OBJECTIVES Previous research suggests black nursing home (NH) residents are more likely to receive inappropriate antipsychotics. Our aim was to examine how NH characteristics, particularly the racial and socioeconomic composition of residents, are associated with the inappropriate use of antipsychotics. DESIGN This study used a longitudinal approach to examine national data from Long-Term Care: Facts on Care in the US (LTCFocUS.org) between 2000 and 2015. We used a multivariate linear regression model with year and state fixed effects to estimate the prevalence of inappropriate antipsychotic use at the NH level. SETTING Free-standing NHs in the United States. PARTICIPANTS The sample consisted of 12 964 NHs. MEASUREMENTS The outcome variable was inappropriate antipsychotic use at the facility level. The primary indicator variables were whether a facility had high proportions of black residents and the percentage of residents with Medicaid as their primary payer. RESULTS NHs with high and low proportions of blacks had similar rates of antipsychotic use in the unadjusted analyses. NHs with high proportions of black residents had significantly lower rates of inappropriate antipsychotic use (β = -2; P

BACKGROUND/OBJECTIVES As the national population of persons living with human immunodeficiency virus (HIV) ages, they will require greater postacute and long-term care use. Little is known about the quality of nursing homes (NHs) to which patients with HIV are admitted. In this study, we assess the association between the number of persons with HIV admitted annually to a given NH (HIV concentration) and that NH's quality outcomes. DESIGN A cross-sectional comparative study. SETTING NHs in nine states, from 2001 to 2012. PARTICIPANTS A total of 46 918 NH-years accounting for 67 301 admissions by patients with HIV. MEASUREMENTS We used 100% Medicaid Analytic Extract, Minimum Dataset 2.0 and 3.0, and Medicare claims from 2001 to 2012 from nine states to examine the association between HIV concentration and NH quality. Persons were classified as HIV positive on the basis of all available data sources, and a NH's percentage of new admissions with HIV was calculated (HIV concentration). We then compared differences in star ratings, rehospitalization rates, NH survey deficiencies, and restraint use by a NH's percentage of admissions with HIV, using linear random effects models. RESULTS After adjusting for NH characteristics, zip code characteristics, and state and year fixed effects, NHs with greater than 0% to 5% of admissions with HIV had a 0.6 lower star rating (P

OBJECTIVES High-need (HN) Medicare beneficiaries heavily use healthcare services at a high cost. This population is heterogeneous, composed of individuals with varying degrees of medical complexity and healthcare needs. To improve healthcare delivery and decrease costs, it is critical to identify the subpopulations present within this population. We aimed to (1) identify distinct clinical phenotypes present within HN Medicare beneficiaries, and (2) examine differences in outcomes between phenotypes. DESIGN Latent class analysis was used to identify phenotypes within a sample of HN fee-for-service (FFS) Medicare beneficiaries aged 65 years and older using Medicare claims and post-acute assessment data. SETTING Not applicable. PARTICIPANTS Two cross-sectional cohorts were used to identify phenotypes. Cohorts included FFS Medicare beneficiaries aged 65 and older who survived through 2014 (n = 415 659) and 2015 (n = 416 643). MEASUREMENTS The following variables were used to identify phenotypes: acute and post-acute care use, functional dependency in one or more activities of daily living, presence of six or more chronic conditions, and complex chronic conditions. Mortality, hospitalizations, healthcare expenditures, and days in the community were compared between phenotypes. RESULTS Five phenotypes were identified: (1) comorbid ischemic heart disease with hospitalization and skilled nursing facility use (22% of the HN sample), (2) comorbid ischemic heart disease with home care use (23%), (3) home care use (12%), (4) high comorbidity with hospitalization (32%), and (5) Alzheimer's disease/related dementias with functional dependency and nursing home use (11%). Mortality was highest in phenotypes 1 and 2; hospitalizations and expenditures were highest in phenotypes 1, 3, and 4. CONCLUSIONS Our findings represent a first step toward classifying the heterogeneity among HN Medicare beneficiaries. Further work is needed to identify modifiable utilization patterns between phenotypes to improve the value of healthcare provided to these subpopulations. J Am Geriatr Soc 68:70-77, 2019.

Histone modifications, largely regulated by histone acetyltransferases (HAT) and histone deacetylases, have been recognized as major regulatory mechanisms governing human diseases, including cancer. Despite significant effort and recent advances, the mechanism by which the HAT and transcriptional coactivator p300 mediates tumorigenesis remains unclear. Here, we use a genetic and chemical approach to identify the microphthalmia-associated transcription factor (MITF) as a critical downstream target of p300 driving human melanoma growth. Direct transcriptional control of MITF by p300-dependent histone acetylation within proximal gene regulatory regions was coupled to cellular proliferation, suggesting a significant growth regulatory axis. Further analysis revealed forkhead box M1 (FOXM1) as a key effector of the p300–MITF axis driving cell growth that is selectively activated in human melanomas. Targeted chemical inhibition of p300 acetyltransferase activity using a potent and selective catalytic p300/CBP inhibitor demonstrated significant growth inhibitory effects in melanoma cells expressing high levels of MITF. Collectively, these data confirm the critical role of the p300–MITF–FOXM1 axis in melanoma and support p300 as a promising novel epigenetic therapeutic target in human melanoma. Significance: These results show that MITF is a major downstream target of p300 in human melanoma whose expression is predictive of melanoma response to small-molecule inhibition of p300 HAT activity.

p300 and CBP are highly related histone acetyltransferase (HAT) enzymes that regulate gene expression, and their dysregulation has been linked to cancer and other diseases. p300/CBP is composed of a number of domains including a HAT domain which is inhibited by the small molecule A-485 and an acetyl-lysine binding bromodomain which was recently found to be selectively antagonized by the small molecule I-CBP112. Here we show that the combination of I-CBP112 and A-485 can synergize to inhibit prostate cancer cell proliferation. We find that the combination confers a dramatic reduction in p300 chromatin occupancy compared to the individual effects of blocking either domain alone. Accompanying this loss of p300 on chromatin, combination treatment leads to the reduction of specific mRNAs including androgen-dependent and pro-oncogenic prostate genes such as KLK3 (PSA) and c-Myc. Consistent with p300 chromatin binding directly affecting gene expression, mRNAs that are significantly reduced by combination treatment also exhibit a strong reduction in p300 chromatin occupancy at their gene promoters. The relatively few mRNAs that are up-regulated upon combination treatment show no correlation with p300 occupancy. These studies provide support for the pharmacologic advantage of concurrent targeting of two domains within one key epigenetic modification enzyme.

This cross-sectional study characterizes Medicare Advantage contract terminations and identifies the characteristics of enrollees who may have been disproportionately affected by these events.

This cross-sectional study compares double bonuses with clinical and administrative performance in Medicare Advantage facilities.