35 research outputs found
Central Nervous System Pseudoprogression in a Patient Treated with PD-1 Checkpoint Inhibitor
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Administrative Data for Policy-Relevant Research: Assessment of Current Utility and Recommendations for Development
The report of the Advisory Panel on the Research Uses of Administrative Data1 is concerned with administrative data collected at the state and local levels in the operation of government programs for the poor, such as AFDC/TANF, Food Stamps, Medicaid, and foster care. In addition to their "record-keeping" function, administrative data increasingly are used to monitor and evaluate program performance and ensure agency accountability.Ray Marshall Center for the Study of Human Resource
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Safety and efficacy of ipilimumab in melanoma patients who received prior immunotherapy on phase III study MDX010-020
9050
Background: MDX010-020 was a phase III comparison of ipilimumab (Ipi), gp100 vaccine or the combination for advanced melanoma. A subset of patients (pts) received other immunotherapy (IM) for advanced disease prior to receiving Ipi, providing the opportunity to evaluate safety and efficacy of Ipi following IM. A prior analysis has shown that pts receiving prior IL-2 had a similar overall survival (OS) to pts who had not received prior IL-2 [Hodi et al NEJM2010]; we now report expanded results for pts receiving any prior IM (interferons and/or interleukin). Methods: Eligible pts (n=676) had unresectable stage III/IV melanoma and were randomized 3:1:1 to q3 wks x 4 doses of Ipi + gp100 or Ipi + placebo or gp100 + placebo. All Ipi doses were 3 mg/kg i.v. OS was retrospectively analyzed for pts receiving any prior IM; immune-related adverse events (irAEs) during induction were evaluated for pts who received any prior IM (322 pts, 48%) and for pts who received prior IL-2 (154 pts, 23%). Results: Demography and OS are summarized below. irAEs of any grade were reported for 60% (Ipi) and 54% (Ipi + gp100) of pts receiving any prior IM. Those receiving prior IL-2 specifically had 73% (Ipi) and 58% (Ipi + gp100) incidence of any grade irAEs. Incidence was similar for those not receiving prior IM or prior IL-2. Diarrhea, rash, and pruritus were the most common events in all groups. Conclusions: Results for OS in this subgroup analysis were similar for both those receiving any prior IM and those who did not receive prior IM and to the overall 020 population. In addition, safety profiles were similar irrespective of prior immunotherapy. Clinical trial information: NCT00094653. [Table: see text
Using theories of action to guide national program evaluation and local strategy in the community care network demonstration
Evaluations of multisite community-based projects are notoriously difficult to conceptualize and conduct. Projects may share an overarching vision but operate in varying contexts and pursue different initiatives. One tool that can assist evaluators facing these challenges is to developa theory of action (TOA) that identifies critical assumptions regarding how a program expects to achieve its goals. Community Care Network (CCN) evaluators used the TOA to refine research questions, define key variables, relate questions to each other, and identify when we might realistically expect to observe answers. In this article, the authors present their national-level CCN TOA. They also worked with sites to helpthem surface their local TOA; the article analyzes the results to determine the content, clarity, extent of evidence base, and strategic orientation of theories articulated by different sites
An End to Perinatal HIV: Success in the US Requires Ongoing and Innovative Efforts that Should Expand Globally
Changes in the Monitoring and Oversight Practices of Not-for-Profit Hospital Governing Boards 1989-2005
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Multi-omic profiling reveals discrepant immunogenic properties and a unique tumor microenvironment among melanoma brain metastases
Abstract Melanoma brain metastases (MBM) are clinically challenging to treat and exhibit variable responses to immune checkpoint therapies. Prior research suggests that MBM exhibit poor tumor immune responses and are enriched in oxidative phosphorylation. Here, we report results from a multi-omic analysis of a large, real-world melanoma cohort. MBM exhibited lower interferon-gamma (IFNγ) scores and T cell-inflamed scores compared to primary cutaneous melanoma (PCM) or extracranial metastases (ECM), which was independent of tumor mutational burden. Among MBM, there were fewer computationally inferred immune cell infiltrates, which correlated with lower TNF and IL12B mRNA levels. Ingenuity pathway analysis (IPA) revealed suppression of inflammatory responses and dendritic cell maturation pathways. MBM also demonstrated a higher frequency of pathogenic PTEN mutations and angiogenic signaling. Oxidative phosphorylation (OXPHOS) was enriched in MBM and negatively correlated with NK cell and B cell-associated transcriptomic signatures. Modulating metabolic or angiogenic pathways in MBM may improve responses to immunotherapy in this difficult-to-treat patient subset
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Multi-omic profiling reveals discrepant immunogenic properties and a unique tumor microenvironment among melanoma brain metastases
Melanoma brain metastases (MBM) are clinically challenging to treat and exhibit variable responses to immune checkpoint therapies. Prior research suggests that MBM exhibit poor tumor immune responses and are enriched in oxidative phosphorylation. Here, we report results from a multi-omic analysis of a large, real-world melanoma cohort. MBM exhibited lower interferon-gamma (IFNγ) scores and T cell-inflamed scores compared to primary cutaneous melanoma (PCM) or extracranial metastases (ECM), which was independent of tumor mutational burden. Among MBM, there were fewer computationally inferred immune cell infiltrates, which correlated with lower TNF and IL12B mRNA levels. Ingenuity pathway analysis (IPA) revealed suppression of inflammatory responses and dendritic cell maturation pathways. MBM also demonstrated a higher frequency of pathogenic PTEN mutations and angiogenic signaling. Oxidative phosphorylation (OXPHOS) was enriched in MBM and negatively correlated with NK cell and B cell-associated transcriptomic signatures. Modulating metabolic or angiogenic pathways in MBM may improve responses to immunotherapy in this difficult-to-treat patient subset