Determinants of overall survival in patients with metastatic uveal melanoma.

BACKGROUND: Despite improvements in the treatment of primary uveal melanoma (UM), patients with metastatic disease continue to exhibit poor survival. METHODS: A retrospective review of metastatic UM patients at Yale (initial cohort) and Memorial Sloan Kettering (validation cohort) was conducted. Cox proportional hazards regression was used to determine baseline factors that are associated with overall survival, including sex, Eastern Cooperative Oncology Group (ECOG) Performance Status Scale, laboratory measurements, metastasis location, and use of anti-CTLA-4 and anti-PD-1 therapies. Differences in overall survival were analyzed using Kaplan-Meier analysis. RESULTS: A total of 89 patients with metastatic UM were identified; 71 and 18, in the initial and validation cohorts, respectively. In the initial cohort, median follow-up was 19.8 months (range, 2-127 months) and median overall survival was 21.8 months (95% CI, 16.6-31.3). Female sex, anti-CTLA-4, and anti-PD-1 therapy were associated with better survival outcomes with adjusted death hazard ratios (HRs) of 0.40 (95% CI, 0.20-0.78), 0.44 (0.20-0.97), and 0.42 (0.22-0.84), respectively, whereas development of hepatic metastases and ECOG score ≥1 (per 1 U/L) were associated with worse survival outcomes with HRs of 2.86 (1.28-7.13) and 2.84 (1.29-6.09), respectively. In both the initial and validation cohorts, use of immune checkpoint inhibitors was associated with improved overall survival after adjusting for sex and ECOG score, with death HRs of 0.22 (0.08-0.56) and 0.04 (0.002-0.26), respectively. CONCLUSIONS: Development of extrahepatic-only metastases, ECOG of 0, immune checkpoint therapy, and female sex were each associated with more than 2-fold reductions in risk of death. PLAIN LANGUAGE SUMMARY: Metastatic uveal melanoma patients face limited treatment options and poor survival rates. Results from this retrospective analysis indicate that immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1 therapies, were associated with improved survival outcomes. Factors such as extrahepatic-only metastases, better baseline performance status, and female sex contributed to a more than 2-fold reduction in death risk. These findings highlight the potential of immunotherapy in treating metastatic uveal melanoma.

Physician responses to apple watch-detected irregular rhythm alerts.

BACKGROUND: While the US Food and Drug Administration (FDA) has cleared smartwatch software for detecting atrial fibrillation (AF), there is lack of guidance on management by physicians. We sought to evaluate the approach to management of Apple Watch alerts for AF by physicians and assess whether respondent and case characteristics were associated with their approach. METHODS: We conducted a case-based survey of physicians practicing primary care, emergency medicine, and cardiology at 2 large academic centers (Yale and University of California San Francisco) between September and December 2021. Cases described asymptomatic patients receiving Apple Watch AF alerts; cases varied in sex, race, medical history, and notification frequency. We evaluated physician responses among prespecified diagnostic testing, referral, and treatment options. RESULTS: We emailed 636 physicians, of whom 95 (14.9%) completed the survey, including 39 primary care, 25 emergency medicine, and 31 cardiology physicians. Among a total of 192 cases (16 unique scenarios), physicians selected at least one diagnostic test in 191 (99.5%) cases and medications in 48 (25.0%). Physicians in primary care, emergency medicine, and cardiology reported varying preference for patient referral (14%, 30%, and 16%, respectively; P=.048), rhythm monitoring (84%, 46%, and 94%, respectively; P<.001), measurement of BNP (8%, 20%, and 2%; P=.003), and use of antiarrhythmics (16%, 4%, and 23%; P=.023). There were few physician differences in reported practices across patient demographics (sex and race), clinical complexity, and alert frequency of the clinical case. CONCLUSIONS: In hypothetical cases of patients presenting without clinical symptoms, physicians opted for further diagnostic testing and often to medical intervention based on Apple Watch irregular rhythm notifications. There was also considerable variation across physician specialties, suggesting a need for uniform clinical practice guidelines. Additional study is required before irregular rhythm notifications should be used in clinical settings.

Validation of the Prognostic Usefulness of the Gene Expression Profiling Test in Patients with Uveal Melanoma.

PURPOSE: To validate the prognostic usefulness of gene expression profile (GEP) testing in patients with uveal melanoma. To determine whether combining tumor size with the GEP classification provides additional prognostic value. DESIGN: Retrospective analysis. PARTICIPANTS: Patients with a diagnosis of choroidal melanoma examined at Yale New Haven Hospital; University of California, San Diego; and Memorial Sloan Kettering Cancer Center. METHODS: Patients' demographic and clinical data and tumor characteristics were collected. Univariate and multivariate Cox hazard regression analysis were used to assess the association between tumor characteristics and GEP classification with metastasis as an outcome. MAIN OUTCOME MEASURES: Metastasis-free survival (MFS). RESULTS: Of the 337 individuals included in the study, 87 demonstrated metastases. The mean follow-up time was 37.2 (standard deviation [SD], 40.2) months for patients with metastases and 55.0 (SD, 49.3) months for those without metastases. Tumors of larger thickness and GEP class 2 (vs. class 1) were associated significantly with increased risk of metastasis. Tumor thickness showed better prognostic usefulness than GEP classification (Wald statistic, 40.7 and 24.2, respectively). Class 2 tumors with a thickness of 7.0 mm or more were associated with increased risk of metastasis than tumors with a thickness of < 7.0 mm (hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.61-6.51), whereas class 1 tumors with a thickness of 9.0 mm or more were associated with increased risk of metastasis than tumors with a thickness of < 9.0 mm (HR, 2.07; 95% CI, 0.86-4.99). No difference in MFS was found between patients with class 1A tumors compared with those with class 1B tumors (P = 0.8). Patients with class 2 tumors showed an observed 5-year MFS of 47.5% (95% CI, 36.0%-62.8%). CONCLUSIONS: Tumor size was the most significant predictor of metastasis and provided additional prognostic value independent of GEP classification. In addition, rates of metastasis for class 2 tumors were lower than estimates reported by Castle Bioscience, and no difference in rates of metastasis were found between class 1A and 1B tumors. This indicates that tumor size should be accounted for when relying on GEP for prognostication and that patients with GEP class 1A or 1B tumors may benefit from the same metastatic surveillance protocols. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Changes in Facility Share of Medicaid-Insured Patients with Urologic Cancers Following Implementation of the Patient Protection and Affordable Care Act.

OBJECTIVES: To examine Medicaid-insurance acceptance at facilities treating urologic cancers following implementation of the Affordable Care Act (ACA). METHODS: We conducted a retrospective, longitudinal study with a pre-post design. We accessed 2010-2017 data from the National Cancer Database, calculating the facility-level change in proportion of urologic cancer patients with Medicaid following implementation of the ACA. We used multivariable logistic regression to assess baseline clinical and demographic factors associated with changes in the proportion of patients at a facility insured through Medicaid. RESULTS: We identified 630 facilities, including 287 in Medicaid expansion states and 343 in non-expansion states associated with 436,082 urologic cancer patients. The mean facility-level change in proportion of patients with Medicaid was +5.8% (95% CI 5.0-6.5%) in expansion states versus +0.6% (95% CI 0.2-0.9%) in non-expansion states. There were 179 facilities that experienced a decrease in the post-ACA period, representing 13.6% of facilities in expansion states and 40.8% in non-expansion states (p<0.001). Factors associated with a decrease in proportion of urologic cancer patients insured by Medicaid included non-expansion state status (OR 8.9, 95% CI 5.3-15.6, p<0.001), higher baseline proportion of patients with Medicaid (highest quartile versus lowest: OR 4.6, 95% CI 2.3-9.4, p<0.001) and high income zip code (highest versus lowest quartile: OR 3.1, 95% CI 1.5-6.6, p<0.001). CONCLUSIONS: Urologic cancer care for Medicaid-insured Americans remains unevenly distributed across cancer care centers, even in states that expanded coverage. Our findings suggest that this variation may reflect the effort of some facilities to reduce their financial exposure to increased numbers of Medicaid patients in the wake of ACA-supported state expansions.

Racial disparities among older adults with acute myocardial infarction: The SILVER-AMI study.

BACKGROUND: Despite an aging population, little is known about racial disparities in aging-specific functional impairments and mortality among older adults hospitalized for acute myocardial infarction (AMI). METHODS: We analyzed data from patients aged 75 years or older who were hospitalized for AMI at 94 US hospitals from 2013 to 2016. Functional impairments and geriatric conditions were assessed in-person during the AMI hospitalization. The association between race and risk of mortality (primary outcome) was evaluated with logistic regression adjusted sequentially for age, clinical characteristics, and measures of functional impairment and other conditions associated with aging. RESULTS: Among 2918 participants, 2668 (91.4%) self-identified as White and 250 (8.6%) as Black. Black participants were younger (80.8 vs 81.7 years; p = 0.010) and more likely to be female (64.8% vs 42.5%; p < 0.001). Black participants were more likely to present with impairments in cognition (37.6% vs 14.5%; p < 0.001), mobility (66.0% vs 54.6%; p < 0.001) and vision (50.1% vs 35.7%; p < 0.001). Black participants were also more likely to report a disability in one or more activities of daily living (22.4% vs 13.0%; p < 0.001) and an unintentional loss of more than 10 lbs in the year prior to hospitalization (37.2% vs 13.0%; p < 0.001). The unadjusted odds of 6-month mortality among Black participants (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.4-2.8) attenuated to non-significance after adjustment for age, clinical characteristics (OR 1.70, 95% CI 1.7, 1.2-2.5), and functional/geriatric conditions (OR 1.5, 95% CI 1.0-2.2). CONCLUSIONS: Black participants had a more geriatric phenotype despite a younger average age, with more functional impairments. Controlling for functional impairments and geriatric conditions attenuated disparities in 6-month mortality somewhat. These findings highlight the importance of systematically assessing functional impairment during hospitalization and also ensuring equitable access to community programs to support post-AMI recovery among Black older adults.

Association Between Private Equity Acquisition of Urology Practices and Physician Medicare Payments.

OBJECTIVE: To assess whether private equity (PE) acquisitions of urology practices were associated with changes in Medicare payments and patient volume. METHODS: We identified PE acquisitions of urology practices through financial databases, industry news outlets, practice websites, and Google search. Using the Centers for Medicare and Medicaid Service's Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (2012-2019), we conducted descriptive statistics and trends analysis to examine whether PE acquisition was associated with changes in Medicare payments and patient volume in comparison to non-PE affiliated urologists within the same states. RESULTS: We identified PE acquisitions of 10 independent urology practices across 6 states during the study period. In the preacquisition period, urologists later joining private-equity groups received greater mean inflation-adjusted Medicare payments ($246,977 vs $160,038; P <.001) and had greater patient volume (839.7 vs 674.2 patients; P = .001) than urologists who did not. In the postacquisition period, PE affiliated urologists had an 11.0% (95% CI: -0.2% to 22.3%) increase in inflation-adjusted Medicare payments (P = .054) and a 12.5% (95% CI: 6.5%-18.6%) increase in patient volume (P <.001). Non-PE affiliated urologists exhibited a 6% decline in Medicare payments (P <.001) and a 2.7% increase in patient volume (P <.001). CONCLUSION: PE affiliated urologists exhibited increases in Medicare payments even prior to acquisition, in contrast to declines for geographically similar, non-PE urologists. These findings may highlight characteristics of practices targeted by PE firms and local practice trends that may further diverge following acquisition.

Exploratory studies of oral and fecal microbiome in healthy human aging.

Growing evidence has linked an altered host fecal microbiome composition with health status, common chronic diseases, and institutionalization in vulnerable older adults. However, fewer studies have described microbiome changes in healthy older adults without major confounding diseases or conditions, and the impact of aging on the microbiome across different body sites remains unknown. Using 16S ribosomal RNA gene sequencing, we reconstructed the composition of oral and fecal microbiomes in young (23-32; mean = 25 years old) and older (69-94; mean = 77 years old) healthy community-dwelling research subjects. In both body sites, we identified changes in minor bacterial operational taxonomic units (OTUs) between young and older subjects. However, the composition of the predominant bacterial species of the healthy older group in both microbiomes was not significantly different from that of the young cohort, which suggests that dominant bacterial species are relatively stable with healthy aging. In addition, the relative abundance of potentially pathogenic genera, such as Rothia and Mycoplasma, was enriched in the oral microbiome of the healthy older group relative to the young cohort. We also identified several OTUs with a prevalence above 40% and some were more common in young and others in healthy older adults. Differences with aging varied for oral and fecal samples, which suggests that members of the microbiome may be differentially affected by aging in a tissue-specific fashion. This is the first study to investigate both oral and fecal microbiomes in the context of human aging, and provides new insights into interactions between aging and the microbiome within two different clinically relevant sites.

Urology Practice Acquisitions by Private Equity Firms from 2011-2021.

INTRODUCTION: Private equity firms have recently acquired several large urology practices in the United States. As little is known about these acquisitions, we sought to characterize trends in urology practice consolidation. METHODS: We compiled urology practice acquisition data via financial databases, news outlets, practice websites, and Internet keyword search for the time period January 1, 2011 through March 15, 2021. For each acquisition, we determined the acquiring group, number of employed urologists, practice locations, and status of ancillary services (pathology, radiology, or surgery centers). We estimated workforce effects based on the 2019 American Urological Association workforce census. RESULTS: We identified 69 independent practice acquisitions in the study period, including 19 (28.4%) by hospital systems, 7 (10.4%) by multispecialty physician groups, 23 (34.3%) by urology practices, and 20 (29.9%) by private equity-backed platforms. Private equity firms initially targeted large urology practices (mean of 60.8±32.6 urologists) with ownership of ancillary services and consolidated local market share through acquisitions of smaller practices (mean of 15.9±14.5 urologists). As of March 2021, we estimate that 7.2% of private practice urologists in the U.S. were employed by one of 5 private equity-backed platforms; over 25% of all urologists practicing in New Jersey and Maryland are employed by a private equity-backed platform. CONCLUSIONS: Private equity acquisitions have accelerated to become a dominant form of urology practice consolidation in recent years and have achieved significant market influence in certain regions. Future research should assess the impact of private equity investment on practice patterns, health outcomes, and expenditures.

Facility-Level Variation in Use of Locoregional Therapy for Metastatic Prostate Cancer.

INTRODUCTION: We sought to understand patient- and institution-level factors associated with use of locoregional therapy for newly diagnosed metastatic prostate cancer in the era before the availability of evidence supporting its efficacy. METHODS: We queried the National Cancer Database to identify patients diagnosed with metastatic prostate adenocarcinoma (stage M1) between 2004 and 2017. We assessed patient factors associated with definitive local therapy with radiotherapy or radical prostatectomy using multilevel logistic regression accounting for clustering within institutions. We further characterized trends in facility-level use and examined institutional factors associated with utilization. RESULTS: We identified 35,933 patients with M1 prostate cancer at 1,188 facilities. A total of 4,146 patients (11.5%) received local therapy for M1 disease (radiation therapy in 3,378 and radical prostatectomy in 768). Use of local treatment was concentrated among a smaller number of facilities: 50% of all local therapy was delivered at 161 facilities (14% of total). At the patient level, uninsured status (OR 0.62, 95% CI 0.49-0.79, p <0.01) and high comorbidity (Charlson-Deyo score, OR 0.39, 95% CI 0.26-0.6, p <0.01) were associated with lower odds of local therapy. High-utilizing facilities (top quartile) were more commonly community centers (OR 1.76, 95% CI 10.7-2.95, p <0.01) and differed by geographic region (South Atlantic vs West South Central region: OR 0.48, 95% CI 0.25-0.88, p=0.02). CONCLUSIONS: In the period before locoregional therapy was supported by clinical practice guidelines, locoregional therapy use varied significantly at the facility level and was driven by a smaller number of high-utilizing facilities. These findings can contextualize expected increase in the use of local therapy for metastatic prostate cancer.

Acceptance of Simulated Adult Patients With Medicaid Insurance Seeking Care in a Cancer Hospital for a New Cancer Diagnosis.

Importance: Although there have been significant increases in the number of US residents insured through Medicaid, the ability of patients with Medicaid to access cancer care services is less well known. Objective: To assess facility-level acceptance of Medicaid insurance among patients diagnosed with common cancers. Design, Setting, and Participants: This national cross-sectional secret shopper study was conducted in 2020 in a random sample of Commission on Cancer-accredited facilities in the United States using a simulated cohort of Medicaid-insured adult patients with colorectal, breast, kidney, and melanoma skin cancer. Exposures: Telephone call requesting an appointment for a patient with Medicaid with a new cancer diagnosis. Main Outcomes and Measures: Acceptance of Medicaid insurance for cancer care. Descriptive statistics, χ2 tests, and multivariable logistic regression models were used to examine factors associated with Medicaid acceptance for colorectal, breast, kidney, and skin cancer. High access hospitals were defined as those offering care across all 4 cancer types surveyed. Explanatory measures included facility-level factors from the 2016 American Hospital Association Annual Survey and Centers for Medicare & Medicaid Services General Information database. Results: A nationally representative sample of 334 facilities was created, of which 226 (67.7%) provided high access to patients with Medicaid seeking cancer care. Medicaid acceptance differed by cancer site, with 319 facilities (95.5%) accepting Medicaid insurance for breast cancer care; 302 (90.4%), colorectal; 290 (86.8%), kidney; and 266 (79.6%), skin. Comprehensive community cancer programs (OR, 0.4; 95% CI, 0.2-0.7; P = .007) were significantly less likely to provide high access to care for patients with Medicaid. Facilities with nongovernment, nonprofit (vs for-profit: OR, 3.5; 95% CI, 1.1-10.8; P = .03) and government (vs for-profit: OR, 6.6; 95% CI, 1.6-27.2; P = .01) ownership, integrated salary models (OR, 2.6; 95% CI, 1.5-4.5; P = .001), and average (vs above-average: OR, 6.4; 95% CI, 1.4-29.6; P = .02) or below-average (vs above-average: OR, 8.4; 95% CI, 1.5-47.5; P = .02) effectiveness of care were associated with high access to Medicaid. State Medicaid expansion status was not significantly associated with high access. Conclusions and Relevance: This study identified access disparities for patients with Medicaid insurance at centers designated for high-quality care. These findings highlight gaps in cancer care for the expanding population of patients receiving Medicaid.

Evaluation of 16S rRNA gene sequencing for species and strain-level microbiome analysis.

The 16S rRNA gene has been a mainstay of sequence-based bacterial analysis for decades. However, high-throughput sequencing of the full gene has only recently become a realistic prospect. Here, we use in silico and sequence-based experiments to critically re-evaluate the potential of the 16S gene to provide taxonomic resolution at species and strain level. We demonstrate that targeting of 16S variable regions with short-read sequencing platforms cannot achieve the taxonomic resolution afforded by sequencing the entire (~1500 bp) gene. We further demonstrate that full-length sequencing platforms are sufficiently accurate to resolve subtle nucleotide substitutions (but not insertions/deletions) that exist between intragenomic copies of the 16S gene. In consequence, we argue that modern analysis approaches must necessarily account for intragenomic variation between 16S gene copies. In particular, we demonstrate that appropriate treatment of full-length 16S intragenomic copy variants has the potential to provide taxonomic resolution of bacterial communities at species and strain level.