tbuckley/cabot-search huggingface dataset:
Relation Between Narrow Networks and Providers of Cancer Care
Authors: Laura Yasaitis, Justin E. Bekelman, Daniel Polsky
Journal: Journal of Clinical Oncology (2017)

Purpose Health insurers offer plans covering a narrow subset of providers in an attempt to lower premiums and compete for consumers. However, narrow networks may limit access to high-quality providers, particularly those caring for patients with cancer. Methods We examined provider networks offered on the 2014 individual health insurance exchanges, assessing oncologist supply and network participation in areas that do and do not contain one of 69 National Cancer Institute (NCI)-Designated Cancer Centers. We characterized a network's inclusion of oncologists affiliated with NCI-Designated Cancer Centers relative to oncologists excluded from the network within the same region and assessed the relationship between this relative inclusion and each network's breadth. We repeated these analyses among networks offered in the same regions as the subset of 27 NCI-Designated Cancer Centers identified as National Comprehensive Cancer Network (NCCN) Cancer Centers. Results In regions containing NCI-Designated Cancer Centers, there were 13.7 oncologists per 100,000 residents and 4.9 (standard deviation [SD], 2.8) networks covering a mean of 39.4% (SD, 26.2%) of those oncologists, compared with 8.8 oncologists per 100,000 residents and 3.2 (SD, 2.1) networks covering on average 49.9% (SD, 26.8%) of the area's oncologists ( P < .001 for all comparisons). There was a strongly significant correlation ( r = 0.4; P < .001) between a network's breadth and its relative inclusion of oncologists associated with NCI-Designated Cancer Centers; this relationship held when considering only affiliation with NCCN Cancer Centers. Conclusion Narrower provider networks are more likely to exclude oncologists affiliated with NCI-Designated or NCCN Cancer Centers. Health insurers, state regulators, and federal lawmakers should offer ways for consumers to learn whether providers of cancer care with particular affiliations are in or out of narrow provider networks.
National Plan for COPD Care
Authors: Jeff Lyon
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Restoration of tumor suppression in vivo by systemic delivery of chemically-modified PTEN mRNA nanoparticles.
Authors: Mohammad Ariful Islam, Yingjie Xu, Harshal Zope, Wuji Cao, Morteza Mahmoudi, Robert Langer, Philip W. Kantoff, Jinjun Shi, Bruce R. Zetter, Omid C. Farokhzad
Journal: Journal of Clinical Oncology (2017)

11582 Background: The onset and maintenance of cancer frequently involves gain of oncogenic function along with loss of tumor suppression. PTEN is a well-characterized tumor suppressor gene that is lost or mutated in many human cancers including ~50% of metastatic castration-resistant prostate cancer (mCRPC). Reintroduction of functional PTEN for mCRPC treatment has proven difficult. Methods: PTEN mRNA was synthesized by in vitro transcription method and modified with ARCA capping and enzymatic polyadenylation, and then substituted with Pseudo-UTP, 5’-Methyl-CTP. A robust self-assembly approach was employed to prepare PTEN mRNA nanoparticles (NPs) using cationic lipid-like compound G0-C14 and PLGA polymer coated with lipid-PEG shell. PTEN expression in tumors and PI3K-AKT pathway were confirmed by IHC and western blot, respectively. Apoptosis was checked by flow cytometry and Tunel assays. In vivo toxicity was studied by hematologic and histologic tests, and immune response. Results: We successfully restored PTEN mRNA to PTEN-null prostate cancer (PCa) cells via systemic delivery of mRNA NPs. These mRNA NPs are stable in serum, demonstrate minimal toxicity, and provide highly effective transfection in PCa cells (substantially higher HA-PTEN expression than plasmid PTEN transfection) and PCa xenograft tumors, leading to ~85% inhibition of tumor cell growth in vitro and in vivo. We also confirm mRNA NP-mediated systemic restoration of PTEN function in PTEN-null PCa and delineate its tumor suppression through inhibition of the PI3K-AKT pathway and enhancement of apoptosis. Conclusions: The work provides proof of principle for the systemic reintroduction of mRNA-based tumor suppressor genes to tumors in vivo. Because PTEN loss is frequent in late-stage PCa, this approach may have feasibility in this patient population. Considering the strong potential of mRNA therapy and the lack of systemic studies of in vivo mRNA transfection of tumors, this study sheds light on the useful application of NP-mediated mRNA delivery for validating tumor suppressors (e.g., PTEN) as a therapeutic target in cancer treatment where loss of a tumor suppressor contributes to the underlying genetic mechanism of cancer.
A Phase I Study of Selinexor in Combination with Daunorubicin and Cytarabine in Patients with Newly Diagnosed Poor-Risk Acute Myeloid Leukemia
Authors: Kendra L. Sweet, Rami S. Komrokji, Eric Padron, Christopher L Cubitt, Leyla Khavarian, Alan F List, David Sallman, Daniel Sullivan, Julio C Chavez, Bijal D. Shah, Jeffrey E. Lancet
Journal: Blood (2016)
Overall survival analysis of the FOXFIRE-SIRFLOX-FOXFIRE global prospective randomized studies of first-line selective internal radiotherapy (SIRT) in patients with liver metastases from colorectal cancer
Authors: Harpreet Wasan, Guy van Hazel, Volker Heinemann, Navesh Sharma, Julien Taieb, Jens Ricke, Marc Peeters, Michael Findlay, Pradeep S. Virdee, Sharon Love, Joanna Moschandreas, Peter Dutton, Val Gebski, Alastair Gray, Dave Price, Geoff Bower, Amir Montazeri, Daniel Swinson, Ewan Brown, Greg Wilson, Sarah Lowndes, Ricky A. Sharma, Peter Gibbs
Journal: Annals of Oncology (2017)
Evaluating the Impact and Cost-Effectiveness of Statin Use Guidelines for Primary Prevention of Coronary Heart Disease and Stroke
Authors: David J. Heller, Pamela G. Coxson, Joanne Penko, Mark J. Pletcher, Lee Goldman, Michelle C. Odden, Dhruv S. Kazi, Kirsten Bibbins-Domingo
Journal: Circulation (2017)

Statins are effective in the primary prevention of atherosclerotic cardiovascular disease. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline expands recommended statin use, but its cost-effectiveness has not been compared with other guidelines.We used the Cardiovascular Disease Policy Model to estimate the cost-effectiveness of the ACC/AHA guideline relative to current use, Adult Treatment Panel III guidelines, and universal statin use in all men 45 to 74 years of age and women 55 to 74 years of age over a 10-year horizon from 2016 to 2025. Sensitivity analyses varied costs, risks, and benefits. Main outcomes were incremental cost-effectiveness ratios and numbers needed to treat for 10 years per quality-adjusted life-year gained.Each approach produces substantial benefits and net cost savings relative to the status quo. Full adherence to the Adult Treatment Panel III guideline would result in 8.8 million more statin users than the status quo, at a number needed to treat for 10 years per quality-adjusted life-year gained of 35. The ACC/AHA guideline would potentially result in up to 12.3 million more statin users than the Adult Treatment Panel III guideline, with a marginal number needed to treat for 10 years per quality-adjusted life-year gained of 68. Moderate-intensity statin use in all men 45 to 74 years of age and women 55 to 74 years of age would result in 28.9 million more statin users than the ACC/AHA guideline, with a marginal number needed to treat for 10 years per quality-adjusted life-year gained of 108. In all cases, benefits would be greater in men than women. Results vary moderately with different risk thresholds for instituting statins and statin toxicity estimates but depend greatly on the disutility caused by daily medication use (pill burden).At a population level, the ACC/AHA guideline for expanded statin use for primary prevention is projected to treat more people, to save more lives, and to cost less compared with Adult Treatment Panel III in both men and women. Whether individuals benefit from long-term statin use for primary prevention depends more on the disutility associated with pill burden than their degree of cardiovascular risk.
A novel method for drug discovery using genomic phenotypes
Authors: Mori Seiichi, Jeffrey Chang, Anil Potti, Joseph Nevins
Journal: Clinical Cancer Research (2007)

A37   Conventional strategies for drug screening make use of either cell-based or molecular target-based screening methods. We describe a genomic phenotype-based screen that makes use of expression signatures combined with the NCI-60 cancer cell line dataset. This dataset includes drug sensitivity measures for over 40,000 compounds together with baseline expression microarray data. Genomic phenotypes, in the form of expression signatures, were developed to represent breast cancer subtypes as well as metastatic potential. Theses signatures were then used to identify cell lines within the panel that exhibit the signature to then connect to compounds that are selectively active against those cells. We identified several compounds, as a proof-of-principle, that are selectively active towards cells with the breast cancer basal subtype. Among these was simvastatin, an HMG-CoA reductase inhibitor, whose activity was confirmed on cultured basal cancer cell lines. This approach provides a novel strategy towards identification of therapeutic agents based on clinically relevant phenotypes.
Smoldering Waldenström’s macroglobulinemia (SWM): Analysis from the National Cancer Database (NCDB).
Authors: Priyanka Avinash Pophali, Adam C. Bartley, Prashant Kapoor, Wilson I. Gonsalves, Aneel A. Ashrani, Ariela L. Marshall, Mustaqeem Ahmad Siddiqui, Ronald S. Go
Journal: Journal of Clinical Oncology (2017)

1573 Background: There are no epidemiologic studies of SWM due to lack ofICD codes specific for smoldering status. Methods: The NCDB represents ~70% of cancer cases in the US. It records the time to initial treatment or reasons for not receiving treatment. Using the 2004-2012 database, we estimated the overall proportion of new adult WM cases that are smoldering and analyzed outcomes according to socio-geo-demographic subgroups. Patients who were recommended treatment (irrespective of administration status) or died within 120 days of diagnosis were considered to have active WM while those who did not require treatment and had follow-up ≥120 days after diagnosis were considered to have SWM. Results: 2322 (28%) of 8302 patients diagnosed with WM were SWM. Median age at diagnosis was 71 (range 28-90) years. Median age did not change significantly during 2004-2012 (P = 0.83) but the proportion of smoldering disease decreased with time (P = 0.02). The proportions of SWM according to socio-geo-demographic subgroups are shown in the Table. Conditional survival (given survival to 4 months) at 5-years was 66% vs. 70% and at 10-years was 38% vs. 46% for active WM vs. SWM, respectively. The OS for SWM was significantly better among females and those who were younger, privately insured, with less co-morbidities and residing closer to a health facility. However, the OS did not differ by racial groups or era of diagnosis 2004-2008 vs 2009-2012. On multivariate analysis, sex, age group and co-morbidity index were significant factors affecting OS while race, insurance, distance from health facility and era of diagnosis were not. Conclusions: Approximately 28% of WM cases in the US are smoldering at diagnosis. The prevalence of SWM varied among socio-geo-demographic subgroups. Sex, age and co-morbidities significantly affect survival of SWM. [Table: see text]
Paclitaxel, carboplatin and trastuzumab (TCH) achieves high pathological complete remission rate after in vivo response directed 2–4 cycles of doxorubicin and cyclophosphamide (AC) in breast cancer patients
Authors: R. S. Mehta, T. Schubbert, K. Kong
Journal: Journal of Clinical Oncology (2006)

10583 Background: A pathological complete remission (pCR) predicts improved survival in breast cancer (BC). Treatment with AC followed by concurrent TCH improved pCR rates to 87.5% in Her2 positive 8-patient pilot study (SABCS 2004, abs #1110), confirmed by a subsequent phase II study. We hypothesized that response adjusted AC (2–4 cycles), TCH (3–4 cycles) sequence targets topoisomerase II alpha amplified and deleted clone, respectively (SABCS 2005, abs # 5056). We report here the combined analysis of the Her2 positive (fluorescence in situ hybridization + or immunohistochemistry 3+) subset of these studies. Material and Methods: Thirty-one patients with stage IIB-IV BC were accrued. Twenty-eight of 31 patients received AC in a dose dense manner with GM-CSF support. Patients received carboplatin calculated at AUC of 2 and paclitaxel at 80 mg/m 2 for 3 weeks followed by 1 week of rest (1 cycle) for a maximum of 4 cycles. Concurrent trastuzumab 4 mg/kg loading dose, then 2 mg/kg/wk was administered for 12–16 weeks. Results: Twenty-nine of 31(94%, CI, 0.79–1) patients showed a clinical complete or partial response (cCR, or cPR). Nineteen of 27 patients (70%, CI, 0.50–0.86) achieved a pCR at surgery; two additional patients had ≤3 mm residual invasive cancer; and lymph node negativity rate was 73%. Of the 3 additional patients with cCR, 1died (underlying cirrhosis), 1 refused surgery, and 1 awaits surgery. A fourth patient with cPR awaits surgery. Ninety percent of the patients (28/31, CI, 0.74–0.98) are alive, and 77% (24/31, CI, 0.59–0. 90) are progression free at median follow up of 19 months (range 6–35 months). Median ejection fraction by echocardiogram was 60% (range 50–74); no patient had clinical cardiac dysfunction. One patient each on GM-CSF and peg-GCSF developed neutropenic fever. Conclusion: Short course of TCH following response adjusted 2–4 cycles of AC will have an improved therapeutic ratio with minimum cardiac toxicity and maximal response. [Table: see text] [Table: see text]
Constitutive resistance to viral infection in human CD141 <sup>+</sup> dendritic cells
Authors: Aymeric Silvin, Chun I Yu, Xavier Lahaye, Francesco Imperatore, Jean-Baptiste Brault, Sylvain Cardinaud, Christian Becker, Wing-Hong Kwan, Cécile Conrad, Mathieu Maurin, Christel Goudot, Santy Marques-Ladeira, Yuanyuan Wang, Virginia Pascual, Esperanza Anguiano, Randy A. Albrecht, Matteo Iannacone, Adolfo García-Sastre, Bruno Goud, Marc Dalod, Arnaud Moris, Miriam Merad, A. Karolina Palucka, Nicolas Manel
Journal: Science Immunology (2017)

Dendritic cells (DCs) are critical for the launching of protective T cell immunity in response to viral infection. Viruses can directly infect DCs, thereby compromising their viability and suppressing their ability to activate immune responses. How DC function is maintained in light of this paradox is not understood. By analyzing the susceptibility of primary human DC subsets to viral infections, we report that CD141+ DCs have an innate resistance to infection by a broad range of enveloped viruses, including HIV and influenza virus. In contrast, CD1c+ DCs are susceptible to infection, which enables viral antigen production but impairs their immune functions and survival. The ability of CD141+ DCs to resist infection is conferred by RAB15, a vesicle-trafficking protein constitutively expressed in this DC subset. We show that CD141+ DCs rely on viral antigens produced in bystander cells to launch cross-presentation-driven T cell responses. By dissociating viral infection from antigen presentation, this mechanism protects the functional capacity of DCs to launch adaptive immunity against viral infection.
Determining the glioma CpG island methylator phenotype, 1p/19q codeletion, and <i>MGMT</i> promoter methylation from epigenome-wide methylation data in the biomarker cohort of the NOA-04 trial.
Authors: Benedikt Wiestler, David Capper, Volker Hovestadt, Martin Sill, David Jones, Christian Hartmann, Joerg Felsberg, Michael Platten, Kathy Keyvani, Stefan Pfister, Otmar Wiestler, Richard Meyermann, Guido Reifenberger, Torsten Pietsch, Andreas von Deimling, Michael Weller, Wolfgang Wick
Journal: Journal of Clinical Oncology (2014)

2017 Background: Molecular biomarkers, including isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation, 1p/19q codeletion and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, improve prognostication and may even guide treatment decisions in patients with World Health Organization (WHO) grade III gliomas. At present, each marker is individually tested by distinct assays. Illumina Infinium HumanMethylation450 BeadChip arrays (HM450) allow the determination of large-scale methylation profiles and genome-wide DNA copy number changes, enabling molecular subgrouping of tumors. Algorithms have been developed to detect the glioma CpG island methylator phenotype (G-CIMP) associated with IDH1/2 mutation, as well as 1p/19q codeletion and MGMTpromoter methylation, using this assay. Methods: Here, we investigated the diagnostic and prognostic performance of these algorithms in the biomarker cohort (n=115 patients) of the NOA-04 trial, which centrally assessed IDH, 1p/19q and MGMTstatus using established single marker tests. Results: Concordance for IDH and 1p/19q status was very high: In 92% of cases, the HM450 and the reference data agreed. In discordant cases, survival analysis by Kaplan-Meier and Cox regression analyses suggested a more accurate assessment of the biological phenotype by HM450 analysis. The HM450-derived MGMT-STP27 model to calculate MGMT promoter methylation probability revealed this aberration in a significantly higher fraction of cases than conventional methylation-specific PCR (MSP), with 87/91 G-CIMP positive tumors predicted as MGMTpromoter-methylated. Fitting a new model for these tumors resulted in an area under the curve of 0.84. Conclusions: G-CIMP and 1p/19q codeletion are reliably detectable by HM450 analysis and associated with prognosis in the NOA-04 trial. Efforts are required to resolve the discrepancy between the MGMT-STP27 and MSP data for MGMT promoter methylation status. Overall, our data suggests that HM450 analysis may be able to replace individual marker tests for routine assessment of anaplastic gliomas.
Abstract 342: Increased Mitochondrial Permeability Transition Pore Opening Dominates Ischemia-Reperfusion Injury in the Aged Female Rat Heart
Authors: Alexandra M Machikas, James C Hunter, Veronica Lopez, Donna H Korzick
Journal: Circulation Research (2012)

Background: Cardiovascular disease remains the leading cause of death in older post-menopausal women. Ischemia/Reperfusion (I/R) injury triggers mitochondrial calcium (Ca 2+ ) overload inducing mitochondrial permeability transition pore (MPTP) opening, mitochondrial dysfunction, and cell death potentially by necrosis, apoptosis, and/or autophagy. Purpose: We sought to determine if age-associated estrogen deficiency increases mitochondrial Ca 2+ sensitivity, providing a possible mechanism for increased vulnerability to I/R injury in older women. Methods: Mitochondrial respiration (MR) was assessed in isolated mitochondria from ventricles of adult (6 mo; n=15) and aged (24 mo; n=18) ovary-intact or ovariectomized (OVX) female F344 rats. MR at complexes I and II was compared in the absence (State 2) and presence (State 3) of ADP to calculate respiratory control index (RCI; state3/state 2). Reduced RCI following Ca 2+ addition was used to assess Ca 2+ sensitivity, while mitochondrial Ca 2+ retention capacity was measured to quantify MPTP opening (CRC; n=4-5/group) prior to and following coronary artery ligation (55 min I and 6 hr R). Apoptosis was examined using DNA laddering and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Markers of autophagy were evaluated by western blotting and mitochondrial morphology through electron microscopy (EM). Results: Significant age-dependent decreases in RCI for complex I (12%) and complex II (8%) were observed in the absence of Ca 2+ , and correlated with increased necrosis in aged hearts revealed by triphenyltetrazolium chloride (TTC) staining (p &lt; 0.05). Ca 2+ exposure decreased MR (18-30%; p &lt; 0.05) in Complex I of aged and OVX mitochondria vs adults. Furthermore, CRC worsened with age requiring less Ca 2+ to open the MPTP. Reduced DNA laddering and TUNEL staining combined with increased beclin-1 and cathepsinD expression in aged vs. adult further support a dominant role for necrosis over apoptosis underlying cell death in aged females (n=4-5/group). EM revealed morphological alterations with age and OVX. Conclusion: Decreased MR and increased MPTP opening with aging are likely causal in necrotic cell death mechanisms associated with I/R injury observed in post-menopausal women.