tbuckley/cabot-search huggingface dataset:
The Association Between Medicare Low-Income Subsidy and Anticancer Treatment Uptake in Advanced Lung Cancer
Authors: Yi-Ting Chou, Joel F Farley, Thomas E Stinchcombe, Amber E Proctor, Jennifer Elston Lafata, Stacie B Dusetzina
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background High out-of-pocket costs may impact anticancer treatment uptake. The Low-Income Subsidy (LIS) program can reduce patient out-of-pocket cost for Medicare Part D–covered treatments. We examined whether the LIS increased uptake and reduced time to initiate orally administered anticancer drugs in patients with advanced non–small cell lung cancer (NSCLC). Methods Using Surveillance, Epidemiology and End Results (SEER)-Medicare data, we identified older adults (aged 65 years and older) diagnosed with advanced NSCLC from 2007 through 2013 and categorized them as full LIS, partial LIS, or non-LIS. We used propensity-score weighted (IPTW) Cox proportional hazards regression to assess the likelihood of and time to initiate Part D treatments. Part B medication uptake was our negative control because supplemental insurance reduces out-of-pocket costs for those drugs. All statistical tests were two-sided. Results Among 19 746 advanced NSCLC patients, approximately 10% initiated Part D treatments. Patients with partial or no LIS were less likely to initiate Part D treatments than were those with full subsidies (partial LIS vs full LIS HRIPTW = 0.77, 95% confidence interval = 0.62 to 0.97; non-LIS vs full LIS HRIPTW = 0.87, 95% confidence interval = 0.79 to 0.95). Time to initiate Part D treatments was also slightly shorter among full-LIS patients (full LIS mean [SD] = 10.8 [0.04] months; partial LIS mean [SD] = 11.3 [0.08] months; and non-LIS mean [SD] = 11.1 [0.03] months, P &amp;lt; .001). Conversely, patients with partial or no LIS had shorter time to initiation of Part B drugs. Conclusions Patients receiving the full LIS had higher orally administered anticancer treatment uptake than patients without LIS. Notably, patients with partial LIS had the lowest treatment uptake, likely because of their low incomes combined with high expected out-of-pocket spending. High out-of-pocket costs for Part D medications may be a barrier to treatment use for patients without full LIS.
Information needs of hematologic cancer survivors
Authors: C. Soloe, K. Bandel, M. Jarblum, E. Willacy, S. Squire, D. Driscoll, J. Kepner, T. Gansler
Journal: Journal of Clinical Oncology (2006)

18547 Background: Little is known about how information needs of cancer survivors/patients (S/P), caregivers (CG), and non-caregiver relatives (NCG) evolve during the cancer experience. Methods: We conducted structured interviews of 21 leukemia, lymphoma, and multiple myeloma S/P, 13 CG, and 19 NCG, and asked them to prioritize information needs during the 4 cancer experience phases from a list of 13 topics. This research was supported by the Division of Cancer Prevention and Control of the Centers for Disease Control and Prevention. Results: Information preferences varied (Friedman’s test, P &lt; 0.0001) by phase of the cancer experience. Topics ranked highest (median rank in parentheses) before treatment, during treatment, after treatment, and at relapse, respectively, were diagnostic tests (2), cancer/ cancer types (2.5), treatment options (3.4), hospitals/cancer centers (3.5), and insurance/financial issues (4); coping with treatment side effects (3), insurance/financial issues (4.5), treatment options (5), hospitals/cancer centers (5), and long term side effects (5); long term side effects (2), tests to detect recurrence (2), risk factors (3), diagnostic tests (4), and support groups (5); and tests to detect recurrence (3), insurance/financial issues (3), cancer/cancer types (4), diagnostic tests (5), and treatment options (5). Across the cancer experience, the highest priority topics for S/P, CG, and NCG, were cancer/ cancer types (4), treatment options (4), long term side effects (5), and risk factors (5); diagnostic tests (4.5), coping with side effects of treatment (5), and treatment options (5); and treatment options (3), diagnostic tests (4), and 5 other topics tied for 3 rd place (6). In-depth, semi-structured interviews conducted with the surveys provided additional detail regarding responses collected in the prioritization exercise. Conclusions: Clinicians can help S/P, CG, and NCG by offering role- and cancer continuum-targeted information. No significant financial relationships to disclose.
Re: Catherine H. Marshall, Alexandra O. Sokolova, Andrea L. McNatty, et al. Differential Response to Olaparib Treatment Among Men with Metastatic Castration-resistant Prostate Cancer Harboring BRCA1 or BRCA2 Versus ATM Mutations. Eur Urol 2019;76:452–8
Authors: Jiayu Liang, Jason M. Beckta, Ranjit S. Bindra
Journal: European Urology (2019)
A preliminary cost-effectiveness analysis of human papillomavirus vaccination in males for the prevention of oropharyngeal cancer.
Authors: Donna M. Graham, Wanrudee Isaranuwatchai, Steven Habbous, Claire de Oliveira, Geoffrey Liu, Lillian L. Siu, Jeffrey S. Hoch
Journal: Journal of Clinical Oncology (2013)

6033 Background: Many western countries have established female human papillomavirus (HPV) vaccination programmes for prevention of cervix cancer. Efficacy against additional HPV-related disease is proven in both sexes, but cost-effectiveness of male vaccination remains controversial. Projected figures suggest incidence and prevalence of oropharyngeal cancer (OPC) in North America will exceed that of cervix cancer by 2020 due to HPV-related cases. Two cost-effectiveness analyses evaluating male HPV vaccination have included OPC, with contrasting results. The Canadian government recommends, but does not fund, male vaccination. In order to assess the value for money of male HPV vaccination in Canada with respect to OPC, we performed a preliminary cost-effectiveness analysis. Methods: Following extensive literature review regarding HPV-related OPC in Canadian males, healthcare cost and clinical effectiveness estimates were obtained from published studies. A Markov model was used to compare potential costs and effectiveness of HPV vaccination against no vaccination among males aged 12 years old. A 3-month cycle length was used with a ‘lifetime’ time horizon. The outcome of the analysis was the incremental cost per quality-adjusted life-year (QALY). Sensitivity analyses were conducted on variables such as vaccine uptake rate and efficacy. Results: Assuming 99% vaccine efficacy and 70% uptake, the use of HPV vaccine produced 0.05 more QALYs and saved $204 Canadian dollars (CAD) per person compared with no vaccine (QALYs and costs discounted at 5% per year). Assuming 50% vaccine efficacy and 50% uptake, use of HPV vaccine produced 0.01 more QALYs and saved $43 CAD. Based on a population of 12 year old males of 192,940 in 2012, male HPV vaccination may potentially save $8.3-39.4 million CAD for this cohort over its lifetime. Conclusions: Knowledge gaps exist regarding male HPV vaccination for OPC prevention. Due to practical limitations, including lack of identifiable precursor lesions in OPC, clinical trials to evaluate this issue may not be feasible. Without considering the effects of herd immunity, this preliminary analysis highlights potential savings from male vaccination.
SETD5 Regulates Chromatin Methylation State and Preserves Global Transcriptional Fidelity during Brain Development and Neuronal Wiring
Authors: Alessandro Sessa, Luca Fagnocchi, Giuseppina Mastrototaro, Luca Massimino, Mattia Zaghi, Marzia Indrigo, Stefano Cattaneo, Davide Martini, Chiara Gabellini, Cecilia Pucci, Alessandra Fasciani, Romina Belli, Stefano Taverna, Massimiliano Andreazzoli, Alessio Zippo, Vania Broccoli
Journal: Neuron (2019)
Injectable hydrogels for the sustained delivery of a HER2-targeted antibody for preventing local relapse of HER2+ breast cancer after breast-conserving surgery
Authors: Xiaobin Chen, Maoli Wang, Xiaowei Yang, Yaoben Wang, Lin Yu, Jian Sun, Jiandong Ding
Journal: Theranostics (2019)

A high risk of local relapse is the main challenge of HER2+ breast cancer after breast-conserving surgery. We aimed to develop a long-acting delivery system for Herceptin, a HER2-targeting antibody, using injectable and thermosensitive hydrogels as the carrier to prevent the local relapse of HER2+ breast tumors while minimizing systemic side effects, especially cardiotoxicity. Methods: Two poly(lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers with different PEG/PLGA proportions were synthesized. Their mixtures with rational mix proportions displayed sol-gel transitions in water with rising of temperature and the Herceptin-loaded hydrogel systems were then prepared. Both the in vivo antitumor and anti-relapse efficacies were evaluated after hypodermic injection of the Herceptin-loaded hydrogel, and the cardiotoxicity was also detected. Results: The gel performance, degradation rate and drug release kinetics of hydrogels were easily adjustable by simply varying the mix proportion. The hydrogel matrix with a specific mix proportion not only avoided initial burst release but also achieved sustained release of Herceptin in vitro for up to 80 days, which is the longest period of Herceptin delivery that has ever been reported. In vivo biodistribution studies performed in SK-BR-3 tumor-bearing mice revealed that a single hypodermic administration of the Herceptin-loaded hydrogel adjacent to the tumor tissue promoted the intratumoral antibody accumulation. This resulted in a better antitumor efficacy compared to weekly hypodermic injections of Herceptin solution for 28 days. A tumor relapse model was also established by imitative breast-conserving surgery on tumor-bearing mice, and both the single injection of the Herceptin-loaded hydrogel and the weekly injection of the Herceptin solution achieved superior anti-relapse efficacy. Furthermore, both antitumor and anti-relapse experiments demonstrated that the weekly pulsed administration of the Herceptin solution caused cardiotoxicity; however, the sustained release of Herceptin from the hydrogel effectively prevented this side effect. Conclusion: The Herceptin-loaded hydrogel has great potential for preventing the relapse of HER2+ breast tumors after breast-conserving surgery with enhanced therapeutic efficacy, improved patient compliance and significantly reduced side effects.
A Genetic Risk Score Associated with Chronic Obstructive Pulmonary Disease Susceptibility and Lung Structure on Computed Tomography
Authors: Elizabeth C. Oelsner, Victor E. Ortega, Benjamin M. Smith, Jennifer N. Nguyen, Ani W. Manichaikul, Eric A. Hoffman, Xiuqing Guo, Kent D. Taylor, Prescott G. Woodruff, David J. Couper, Nadia N. Hansel, Fernando J. Martinez, Robert Paine, Meilan K. Han, Christopher Cooper, Mark T. Dransfield, Gerard Criner, Jerry A. Krishnan, Russell Bowler, Eugene R. Bleecker, Stephen Peters, Stephen S. Rich, Deborah A. Meyers, Jerome I. Rotter, R. Graham Barr
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Chronic obstructive pulmonary disease (COPD) has been associated with numerous genetic variants, yet the extent to which its genetic risk is mediated by variation in lung structure remains unknown.Objectives: To characterize associations between a genetic risk score (GRS) associated with COPD susceptibility and lung structure on computed tomography (CT).Methods: We analyzed data from MESA Lung (Multi-Ethnic Study of Atherosclerosis Lung Study), a U.S. general population-based cohort, and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). A weighted GRS was calculated from 83 SNPs that were previously associated with lung function. Lung density, spatially matched airway dimensions, and airway counts were assessed on full-lung CT. Generalized linear models were adjusted for age, age squared, sex, height, principal components of genetic ancestry, smoking status, pack-years, CT model, milliamperes, and total lung volume.Measurements and Main Results: MESA Lung and SPIROMICS contributed 2,517 and 2,339 participants, respectively. Higher GRS was associated with lower lung function and increased COPD risk, as well as lower lung density, smaller airway lumens, and fewer small airways, without effect modification by smoking. Adjustment for CT lung structure, particularly small airway measures, attenuated associations between the GRS and FEV1/FVC by 100% and 60% in MESA and SPIROMICS, respectively. Lung structure (P < 0.0001), but not the GRS (P > 0.10), improved discrimination of moderate-to-severe COPD cases relative to clinical factors alone.Conclusions: A GRS associated with COPD susceptibility was associated with CT lung structure. Lung structure may be an important mediator of heritability and determinant of personalized COPD risk.
Sacrospinous hysteropexy versus vaginal hysterectomy with uterosacral ligament suspension in women with uterine prolapse stage 2 or higher: observational follow-up of a multicentre randomised trial
Authors: Sascha F M Schulten, Renée J Detollenaere, Jelle Stekelenburg, Joanna IntHout, Kirsten B Kluivers, Hugo W F van Eijndhoven
Journal: BMJ (2019)

To evaluate the effectiveness and success of uterus preserving sacrospinous hysteropexy as an alternative to vaginal hysterectomy with uterosacral ligament suspension in the surgical treatment of uterine prolapse five years after surgery.Observational follow-up of SAVE U (sacrospinous fixation versus vaginal hysterectomy in treatment of uterine prolapse ≥2) randomised controlled trial.Four non-university teaching hospitals, the Netherlands.204 of 208 healthy women in the initial trial (2009-12) with uterine prolapse stage 2 or higher requiring surgery and no history of pelvic floor surgery who had been randomised to sacrospinous hysteropexy or vaginal hysterectomy with uterosacral ligament suspension. The women were followed annually for five years after surgery. This extended trial reports the results at five years.Prespecified primary outcome evaluated at five year follow-up was recurrent prolapse of the uterus or vaginal vault (apical compartment) stage 2 or higher evaluated by pelvic organ prolapse quantification system in combination with bothersome bulge symptoms or repeat surgery for recurrent apical prolapse. Secondary outcomes were overall anatomical failure (recurrent prolapse stage 2 or higher in apical, anterior, or posterior compartment), composite outcome of success (defined as no prolapse beyond the hymen, no bothersome bulge symptoms, and no repeat surgery or pessary use for recurrent prolapse), functional outcome, quality of life, repeat surgery, and sexual functioning.At five years, surgical failure of the apical compartment with bothersome bulge symptoms or repeat surgery occurred in one woman (1%) after sacrospinous hysteropexy compared with eight women (7.8%) after vaginal hysterectomy with uterosacral ligament suspension (difference-6.7%, 95% confidence interval -12.8% to-0.7%). A statistically significant difference was found in composite outcome of success between sacrospinous hysteropexy and vaginal hysterectomy (89/102 (87%) v 77/102 (76%). The other secondary outcomes did not differ. Time-to-event analysis at five years showed no differences between the interventions.At five year follow-up significantly less anatomical recurrences of the apical compartment with bothersome bulge symptoms or repeat surgery were found after sacrospinous hysteropexy compared with vaginal hysterectomy with uterosacral ligament suspension. After hysteropexy a higher proportion of women had a composite outcome of success. Time-to-event analysis showed no differences in outcomes between the procedures.trialregister.nl NTR1866.
Unlocking Personalized Biomedicine and Drug Discovery with Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes: Fit for Purpose or Forever Elusive?
Authors: Tessa de Korte, Puspita A. Katili, Nurul A.N. Mohd Yusof, Berend J. van Meer, Umber Saleem, Francis L. Burton, Godfrey L. Smith, Peter Clements, Christine L. Mummery, Thomas Eschenhagen, Arne Hansen, Chris Denning
Journal: The Annual Review of Pharmacology and Toxicology (2019)

In recent decades, drug development costs have increased by approximately a hundredfold, and yet about 1 in 7 licensed drugs are withdrawn from the market, often due to cardiotoxicity. This review considers whether technologies using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could complement existing assays to improve discovery and safety while reducing socioeconomic costs and assisting with regulatory guidelines on cardiac safety assessments. We draw on lessons from our own work to suggest a panel of 12 drugs that will be useful in testing the suitability of hiPSC-CM platforms to evaluate contractility. We review issues, including maturity versus complexity, consistency, quality, and cost, while considering a potential need to incorporate auxiliary approaches to compensate for limitations in hiPSC-CM technology. We give examples on how coupling hiPSC-CM technologies with Cas9/CRISPR genome engineering is starting to be used to personalize diagnosis, stratify risk, provide mechanistic insights, and identify new pathogenic variants for cardiovascular disease.
A double-blind placebo-controlled randomized phase II trial assessing the activity and safety of regorafenib (REG) in patients (pts) with nonadipocytic soft tissue sarcoma (STS) previously treated with pazopanib (PAZ).
Authors: Nicolas Penel, Jean-Yves Blay, Jennifer Wallet, Isabelle Laure Ray-Coquard, Axel Le Cesne, Thomas Ryckewaert, Antoine Italiano, Sebastien Salas, Corinne Delcambre, Emmanuelle Bompas, Francois Bertucci, Esma Saada-Bouzid, Loic Chaigneau, Christine Chevreau, Julien Thery, Emilie Decoupigny, Marie Vanseymortier, Marie-Cecile Le Deley, Olivier Mir
Journal: Journal of Clinical Oncology (2019)

11021 Background: After we demonstrated the activity of REG in pts with advanced non-adipocytic STS (MirTLO 2016), we conducted a dedicated study in pts previously treated with PAZ+chemo. Methods: We report here the 5th cohort of a double-blind randomized phase 2 trial (NCT01900743). Pts were treated with regorafenib (160mg/d, 21/28d) or placebo (PB). Pts receiving placebo were offered optional cross-over in case of centrally confirmed disease progression. The primary endpoint was centrally-reviewed RECIST-based progression-free survival (PFS), evaluated on the intent-to-treat dataset. A total of 24 events was required to ensure a 90%-power for HR = 0.33 (median PFS, 3·6 vs 1·2 months), with a 1-sided α = 0·1. Overall survival (OS) was a secondary endpoint. Results: From 12/2015 to 10/2017, 37 pts were randomized (18 REG vs 19 PB) and included in the final analysis. The median age was 60 (36-76). There were 28 women (76%). All pts had a performance status 0 or 1. Histological subtypes included 24 leiomyosarcoma (11 vs 13, in REG and PB, respectively), 1 synovial sarcoma (REG), 12 other sarcoma (7 vs 5). All pts had previously been treated with PAZ +chemo (including doxorubicin: 19 vs 17; ifosfamide: 11 vs 3; trabectedin: 11 vs 9; and dacarbazine: 7 vs 6), with 2-6 prior lines. The median relative dose intensity of REG was 0·86, range 0·41-1. Out of 19 pts assigned to placebo, 13 switched to REG after progression. There was no reported objective response. We observed a significant benefit of REG compared to PB in terms of PFS (HR = 0·38; 95%CI, 0·19-0·76; p = 0·007; median PFS = 2·1 vs 1·1 months, respectively), and OS despite the cross-over (HR = 0·41; 95%CI, 0·17-0·98; p = 0·04; median OS = 18·6 vs 8·2 months). Before cross-over, the most common clinically significant grade 3 or higher adverse events were diarrhea (4 vs 0), dyspnea (3 vs 1), arterial hypertension (2 vs 0), hand-foot skin reaction (2 vs 0). Conclusions: The present study demonstrates that regorafenib has a clinically meaningful anti-tumor activity in pts with non-adipocytic soft tissue sarcoma pretreated by both chemotherapy and pazopanib, improving PFS and OS. Clinical trial information: NCT01900743.
Kras/ADAM17-Dependent Jag1-ICD Reverse Signaling Sustains Colorectal Cancer Progression and Chemoresistance
Authors: Maria Pelullo, Francesca Nardozza, Sabrina Zema, Roberta Quaranta, Carmine Nicoletti, Zein Mersini Besharat, Maria Pia Felli, Bruna Cerbelli, Giulia d'Amati, Rocco Palermo, Carlo Capalbo, Claudio Talora, Lucia Di Marcotullio, Giuseppe Giannini, Saula Checquolo, Isabella Screpanti, Diana Bellavia
Journal: Cancer Research (2019)

Colorectal cancer is characterized by well-known genetic defects and approximately 50% of cases harbor oncogenic Ras mutations. Increased expression of Notch ligand Jagged1 occurs in several human malignancies, including colorectal cancer, and correlates with cancer progression, poor prognosis, and recurrence. Herein, we demonstrated that Jagged1 was constitutively processed in colorectal cancer tumors with mutant Kras, which ultimately triggered intrinsic reverse signaling via its nuclear-targeted intracellular domain Jag1-ICD. This process occurred when Kras/Erk/ADAM17 signaling was switched on, demonstrating that Jagged1 is a novel target of the Kras signaling pathway. Notably, Jag1-ICD promoted tumor growth and epithelial-mesenchymal transition, enhancing colorectal cancer progression and chemoresistance both in vitro and in vivo. These data highlight a novel role for Jagged1 in colorectal cancer tumor biology that may go beyond its effect on canonical Notch activation and suggest that Jag1-ICD may behave as an oncogenic driver that is able to sustain tumor pathogenesis and to confer chemoresistance through a noncanonical mechanism. SIGNIFICANCE: These findings present a novel role of the transcriptionally active Jag1-ICD fragment to confer and mediate some of the activity of oncogenic KRAS.
Abstract 15565: Alterations in ROS-NO Signaling in Exercising Swine With Multiple Comorbidities
Authors: Oana Sorop, Jens van de Wouw, Ruben W van Drie, Jaap A Joles, Daphne Merkus, Dirk J Duncker
Journal: Circulation (2018)

Introduction: Multiple comorbidities, such as diabetes mellitus (DM), hypercholesterolemia and chronic kidney disease (CKD) cause inflammation and alterations in coronary microvascular NO bioavaila...
A Text-Book of Medicine, for Students and Practitioners.
Journal: JAMA (1893)

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
Image Gallery: Segmental neurofibromatosis type 1 on the face. A 30‐year delay in diagnosis
Authors: E. Vergara‐de Caso, L. Schneller‐Pavelescu, M.C. Martínez‐Hergueta, P.J. Álvarez‐Chinchilla, I. Poveda‐Montoyo, J. Bañuls
Journal: British Journal of Dermatology (2019)