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Renal medullary carcinoma (RMC) is one of the most aggressive renal cell carcinomas. It predominantly afflicts young adults and adolescents with sickle cell trait and other sickle hemoglobinopathies, and is refractory to targeted and antiangiogenic therapies used in patients with clear-cell renal cell carcinoma. Platinum-based cytotoxic chemotherapy is the mainstay for RMC treatment. On the basis of recent advances in the diagnosis, management, and clinical trial development for RMC, a panel of experts met in October 2017 and developed updated consensus recommendations to inform clinicians, researchers, and patients. Because RMC often aggressively recurs while patients are still recovering from nephrectomy, upfront chemotherapy should be considered for most patients, including those with localized disease. After safety and dosing information has been established in adults, phase II and III trials enrolling patients with RMC should allow patients aged 12 years and older to be accrued. Patients with the very rare unclassified renal cell carcinoma with medullary phenotype variant should be included in RMC trials. Medical providers should be aware that RMC can afflict subjects of all races, and not only those of African descent, and that the presence of sickle cell trait, or of other sickle hemoglobinopathies, can affect drug responses and toxicity.
Copyright © 2018 Elsevier Inc. All rights reserved.
Importance - Modern prevention guidelines substantially increase the number of individuals who are eligible for treatment with statins. Efforts to refine statin eligibility via coronary calcification have been studied in white populations but not, to our knowledge, in large African American populations.
Objective - To compare the relative accuracy of US Preventive Services Task Force (USPSTF) and American College of Cardiology/American Heart Association (ACC/AHA) recommendations in identifying African American individuals with subclinical and clinical atherosclerotic cardiovascular disease (ASCVD).
Design, Setting, and Participants - In this prospective, community-based study, 2812 African American individuals aged 40 to 75 years without prevalent ASCVD underwent assessment of ASCVD risk. Of these, 1743 participants completed computed tomography.
Main Outcomes and Measures - Nonzero coronary artery calcium (CAC) score, abdominal aortic calcium score, and incident ASCVD (ie, myocardial infarction, ischemic stroke, or fatal coronary heart disease).
Results - Of the 2812 included participants, the mean (SD) age at baseline was 55.4 (9.4) years, and 1837 (65.3%) were female. The USPSTF guidelines captured 404 of 732 African American individuals (55.2%) with a CAC score greater than 0; the ACC/AHA guidelines identified 507 individuals (69.3%) (risk difference, 14.1%; 95% CI, 11.2-17.0; P < .001). Statin recommendation under both guidelines was associated with a CAC score greater than 0 (odds ratio, 5.1; 95% CI, 4.1-6.3; P < .001). While individuals indicated for statins under both guidelines experienced 9.6 cardiovascular events per 1000 patient-years, those indicated under only ACC/AHA guidelines were at low to intermediate risk (4.1 events per 1000 patient-years). Among individuals who were statin eligible by ACC/AHA guidelines, the 10-year ASCVD incidence per 1000 person-years was 8.1 (95% CI, 5.9-11.1) in the presence of CAC and 3.1 (95% CI, 1.6-5.9) without CAC (P = .02). While statin-eligible individuals by USPSTF guidelines did not have a significantly higher 10-year ASCVD event rate in the presence of CAC, African American individuals not eligible for statins by USPSTF guidelines had a higher ASCVD event rate in the presence of CAC (2.8 per 1000 person-years; 95% CI, 1.5-5.4) relative to without CAC (0.8 per 1000 person-years; 95%, CI 0.3-1.7) (P = .03).
Conclusions and Relevance - The USPSTF guidelines focus treatment recommendations on 38% of high-risk African American individuals at the expense of not recommending treatment in nearly 25% of African American individuals eligible for statins by ACC/AHA guidelines with vascular calcification and at low to intermediate ASCVD risk.
Under the Affordable Care Act (ACA), changes in income and family circumstances are likely to produce frequent transitions in eligibility for Medicaid and health insurance Marketplace coverage for low- and middle-income adults. We provide state-by-state estimates of potential eligibility changes ("churning") if all states expanded Medicaid under health reform, and we identify predictors of rates of churning within states. Combining longitudinal survey data with state-specific weighting and small-area estimation techniques, we found that eligibility changes occurred frequently in all fifty states. Higher-income states and states that had more generous Medicaid eligibility criteria for nonelderly adults before the ACA experienced more churning, although the differences were small. Even in states with the least churning, we estimated that more than 40 percent of adults likely to enroll in Medicaid or subsidized Marketplace coverage would experience a change in eligibility within twelve months. Policy options for states to reduce the frequency and impact of coverage changes include adopting twelve-month continuous eligibility for adults in Medicaid, creating a Basic Health Program, using Medicaid funds to subsidize Marketplace coverage for low-income adults, and encouraging the same health insurers to offer plans in Medicaid and the Marketplaces.
Under the Affordable Care Act, people who meet certain income eligibility criteria will be eligible for subsidies to offset costs of premiums and cost sharing for health insurance plans purchased through new health insurance exchanges. But determining the correct level of these subsidies will not be easy, because of several factors. These include the way in which eligibility will be calculated for participation in Medicaid or for subsidies through the exchanges; possibly inaccurate income projections; the use of different income time periods to determine eligibility; and fluctuations in income. I performed a simulation that shows that under the most likely methods to be used to determine eligibility for Medicaid or for receiving subsidies through exchanges, one-third of people with incomes initially judged to be below the Medicaid threshold would actually "churn" into an exchange at the end of the year. Other people would be wrongly deemed ineligible for advance subsidy payments because their projected income was too high, while still others judged eligible for subsidies would receive advance payments on those subsidies that were too high by $208 per year, on average. To reduce these errors, I recommend the adoption of a single eligibility standard based on income data derived from prior tax returns, along with generous accommodations during a given enrollment year for people who claim a change in circumstances, such as a change in income.
The objective of this study was to determine if an association existed between the mid-2005 TennCare (Medicaid) disenrollment and increases in uninsured ambulatory care sensitive condition (ACSC) non-admitted ER visits and inpatient hospitalizations in Davidson County, Tennessee (= the city of Nashville). Logistic regression modeling, using an interactive term for insurance category x year, indicated that the effect of no insurance on ACSC ER visits increased by 18% from 2003 to 2007 (p<.001), but no significant effect was found for uninsured ACSC inpatient hospitalizations. These greater odds of ACSC ER visits among uninsured patients were associated with a 60% increase in hospitals' bad debt write offs during this same time period. Therefore, the TennCare disenrollment was associated with increased likelihood of uninsured ACSC non-admitted ER visits and greater financial losses for Davidson County hospitals during this time period.
BACKGROUND - Enrollment of patients with lung cancer into clinical trials is required to accelerate the pace of new therapy development and contribute to a better understanding of the biological characteristics of cancer.
METHODS - We conducted a retrospective chart review of all patients seen by the thoracic medical oncology team at the Vanderbilt Ingram Cancer Center (VICC) from November 2005 to November 2008 to determine the barriers associated with patient enrollment in to clinical trials.
RESULTS - One thousand forty-three patient charts were audited: 32% of patients were eligible for enrollment, and 14% enrolled in a study. There were no significant differences in protocol availability or eligibility by sex, smoking status, or age. Patients living further from the cancer center were significantly less likely to have a study protocol available (P = .009), but if a protocol was available they were more likely to be eligible for enrollment (P < .001). Significantly more protocols were available for patients with non-small-cell lung cancer (NSCLC) compared with those who had small-cell lung cancer (SCLC) (63% vs. 48%; P < .001). Patients with advanced disease were more likely to have a protocol available (P < .001) and enter a study (P = .031). The most common reasons for patients not being eligible for enrollment were poor performance status (32%) and presence of comorbid disease (27%). The most common reasons for potentially eligible patients not enrolling in a study included preference for treatment closer to home (49%) and patient refusal (43%).
CONCLUSION - Additional strategies are required to increase accrual of patients into lung cancer trials, including development of protocols for early-stage disease and modifying eligibility and performance status criteria for this unique patient population.
Copyright © 2013 Elsevier Inc. All rights reserved.
PURPOSE - Knowledge of tumor mutation status is becoming increasingly important for the treatment of cancer, as mutation-specific inhibitors are being developed for clinical use that target only sub-populations of patients with particular tumor genotypes. Melanoma provides a recent example of this paradigm. We report here development, validation, and implementation of an assay designed to simultaneously detect 43 common somatic point mutations in 6 genes (BRAF, NRAS, KIT, GNAQ, GNA11, and CTNNB1) potentially relevant to existing and emerging targeted therapies specifically in melanoma.
METHODS - The test utilizes the SNaPshot method (multiplex PCR, multiplex primer extension, and capillary electrophoresis) and can be performed rapidly with high sensitivity (requiring 5-10% mutant allele frequency) and minimal amounts of DNA (10-20 nanograms). The assay was validated using cell lines, fresh-frozen tissue, and formalin-fixed paraffin embedded tissue. Clinical characteristics and the impact on clinical trial enrollment were then assessed for the first 150 melanoma patients whose tumors were genotyped in the Vanderbilt molecular diagnostics lab.
RESULTS - Directing this test to a single disease, 90 of 150 (60%) melanomas from sites throughout the body harbored a mutation tested, including 57, 23, 6, 3, and 2 mutations in BRAF, NRAS, GNAQ, KIT, and CTNNB1, respectively. Among BRAF V600 mutations, 79%, 12%, 5%, and 4% were V600E, V600K, V600R, and V600M, respectively. 23 of 54 (43%) patients with mutation harboring metastatic disease were subsequently enrolled in genotype-driven trials.
CONCLUSION - We present development of a simple mutational profiling screen for clinically relevant mutations in melanoma. Adoption of this genetically-informed approach to the treatment of melanoma has already had an impact on clinical trial enrollment and prioritization of therapy for patients with the disease.
Our objective was (1) to identify the subgroup of women most affected by the regulatory change expanding Tennessee Medicaid eligibility for pregnant women from 45% of the federal poverty level to 100% and (2) to examine whether increased enrollment correlated with greater use of prenatal care and improved reproductive outcomes. We linked Tennessee birth and fetal death certificates to Medicaid enrollment files. We compare outcome rates in the 12-month period before the change in the Medicaid regulations with similar rates for the 10-month period after the change had been in effect nine months. We found the increase in Medicaid enrollment that occurred after the expansion was greatest for teenage mothers. Among teens, Medicaid enrollment increased 18%, and the odds of receiving no prenatal care or only late (third-trimester) care were reduced 16% (95% confidence interval = 8%, 24%) after we controlled for potential confounders. However, there was no improvement in first-trimester use of prenatal care or in birth outcomes. This finding suggests the need to evaluate carefully subsequent regulatory changes, which sought to promote early prenatal care by removing barriers to early Medicaid enrollment in pregnancy.
OBJECTIVES - "Presumptive eligibility" permits pregnant prospective Medicaid enrollees to obtain services during the application period. The purpose of this study was to assess the effects of presumptive eligibility on the receipt of prenatal care and the occurrence of low-birthweight births and neonatal, perinatal, and infant mortality.
METHODS - Outcome rates for pregnant women who enrolled in Tennessee Medicaid in the 6-month period before presumptive eligibility was enacted were compared with those obtained for pregnant women who enrolled in the 6-month period after presumptive eligibility had been in effect for 5 months.
RESULTS - Women in the "after" group were 40% more likely to enroll and 30% more likely to obtain prenatal care in the first trimester. They were 300% more likely to fill a prescription for prenatal vitamins in the first trimester and 16% more likely to have begun prenatal care before the third trimester. However, they were similar to those enrolling in the "before" time period in terms of the occurrence of adverse perinatal outcomes.
CONCLUSIONS - When barriers to prenatal care, including bureaucratic ones, are removed, low-income women will seek care earlier and more frequently.
To investigate the effects of a 1985 Tennessee Medicaid regulatory change that expanded eligibility coverage specifically for married women during pregnancy, we studied vital statistics files linked to Medicaid enrollment files. The greatest Medicaid coverage increase in terms of an absolute difference in rates and the number of women covered occurred in white married women younger than 25 years with less than 12 years of education, where enrollment increased 18%. However, in that group of mothers, as well as for the total of all mothers studied, there were no concomitant improvements in use of early prenatal care, birth weight, or neonatal mortality. Analysis of the timing of enrollment relative to the beginning of pregnancy showed that more than two thirds of the women who enrolled did so after the first trimester.