tbuckley/cabot-search huggingface dataset:
Adherence to hormonal therapy among commercially insured breast cancer patients.
Authors: Hui Zhao, Xiudong Lei, Mariana Chavez-MacGregor, Weiguo He, Jiangong Niu, Sharon Hermes Giordano
Journal: Journal of Clinical Oncology (2018)

532 Background: Tamoxifen and aromatase inhibitors (AI) are adjuvant hormone therapy (HT) routinely used for the treatment of early-stage estrogen-positive breast cancer, their use reduces the risk of breast cancer recurrence by about 30%. Despite the survival benefit, the side effects of HT and other factors may affect patients' adherence. No large observational study has assessed the 5 year HT adherence for breast cancer. We evaluated HT adherence over a five-year course using the commercial health claims data provided by Truven Health Analytics. Methods: Breast cancer patients who received mastectomy or lumpectomy aged 18 years and older between 1999 to 2014 and initiated HT within 1 year since surgery were selected. The outcome variable was HT adherence rate from years 1 to 5. HT adherence was defined as proportion of days covered (PDC) ≥ 80% during a treatment year. HT adherence rate was computed as adherence patients in a given year divided by all HT users who had insurance coverage in that year. Covariates included patient's age, geographic region, type of health insurance plan, year at cancer surgery, comorbidity, type of HT drugs, and primary cancer treatment such as surgery, chemotherapy, and radiation treatment. Logistic regression was used to evaluate factors associated with HT adherence. Results: 27,790 patients initiated HT within 1 year of breast cancer surgery. The median age was 55 years old and the median time from breast cancer surgery to HT initiation was 114 days. 29.2% of patients used tamoxifen, 28.2% used anastrozole, 8.9% used letrozole, 1.4% used exemestane, and 32.3% used more than one type of HT drugs. Each year, about 60 to 70% patients were adherent to the treatment. The five year adherence rate decreased from 81.4% in the first year to 21.1% in the 5th year. Patients who were ≥ 50 years old, lived not in the South, with insurance other than HMO, received lumpectomy or mastectomy combined with chemotherapy and radiation therapy, with no comorbidity, used AI, and received surgery in 2003 were more likely to be adherent to HT. Conclusions: The five year HT adherence rates were low among breast cancer patients. Health care providers need to identify ways to improve HT adherence to prevent breast cancer recurrence. [1996 characters]
Abstract 2: MANF, A Structurally Unique Redox-Sensitive Chaperone, Restores ER Protein Folding in the Ischemic Heart.
Authors: Adrian Arrieta, Erik A Blackwood, Winston T Stauffer, Michelle Santo Domingo, Amber N Pentoney, Donna J Thuerauf, Shirin Doroudgar, Christopher C Glembotski
Journal: Circulation Research (2017)

Rationale: In cardiomyocytes, most secreted and membrane proteins are synthesized and folded in the sarcoplasmic/endoplasmic reticulum (SR/ER). We previously showed that during myocardial ischemia, decreased oxygen creates a reducing environment in the SR/ER, preventing protein disulfide isomerases (PDIs) from forming disulfide bonds in nascent proteins, causing ER stress, i.e. the toxic accumulation of unfolded proteins which contributes to cardiomyocyte death. In response to ER stress, the transcription factor, ATF6 induces chaperones that restore SR/ER protein folding. We found that ATF6 also induces mesencephalic astrocyte-derived neurotrophic factor (MANF), a recently identified protein of unknown function. MANF is structurally unique, so its function cannot be inferred from other proteins. Since MANF is induced by ATF6, is ER-localized, and contains a conserved redox-sensitive motif found in PDIs, we hypothesized that MANF is a redox-sensitive chaperone that optimizes cardiomyocyte viability during ischemia. Methods: The redox status of MANF during reductive ER stress and the ability of MANF to bind misfolded proteins during ischemia were assessed in neonatal rat ventricular myocytes (NRVM). The ability of recombinant MANF to suppress aggregation of misfolded proteins was examined in an in vitro chaperone assay. Finally, the effects of MANF loss-of-function in the ischemic heart, in vivo , were determined by generating a transgenic mouse model that expresses a cardiomyocyte-specific MANF-targeted microRNA. Results: In NRVM subjected to ER stress MANF was as sensitive to changes in ER redox status as the sentinel PDI, PDIA1. Moreover, MANF formed disulfide-linked complexes with misfolded proteins during ischemia-mediated ER stress. Under reducing conditions, recombinant MANF suppressed aggregation of model misfolded proteins, in vitro . MANF knockdown in the heart, in vivo , increased damage from myocardial infarction, and an AAV9-based gene therapy approach rescued the effects of MANF deficiency, in vivo. Conclusions: MANF is a redox-sensitive SR/ER-resident chaperone that is a critical contributor to SR/ER protein folding during the adaptive ER stress response and decreases tissue damage in the ischemic heart.
Dengue serosurvey after a 2-month long outbreak in Nîmes, France, 2015: was there more than met the eye?
Authors: Tiphanie Succo, Harold Noël, Birgit Nikolay, Marianne Maquart, Amandine Cochet, Isabelle Leparc-Goffart, Olivier Catelinois, Henrik Salje, Camille Pelat, Perrine de Crouy-Chanel, Henriette de Valk, Simon Cauchemez, Cyril Rousseau
Journal: Eurosurveillance (2018)

Background Clusters of dengue cases have recently become more frequent in areas of southern France colonised by the vector mosquito Aedes albopictus . In July 2015, a 2-month outbreak of dengue virus serotype 1 (DENV-1) was reported in Nîmes. Aim: We conducted a serosurvey in the affected area at the end of the vector activity period to determine the true extent of dengue transmission. Methods: We collected capillary blood from consenting household members, and information on their medical and travel histories, and exposure to mosquito bites. Recent infections were identified using IgM and IgG anti-DENV ELISA, followed, when positive, by plaque reduction neutralisation tests on serum against DENV 1–4 and West Nile virus. The prevalence estimator was calibrated on reference demographic data. We quantified the spatial clustering of dengue cases within the affected community and inferred the transmission tree. Results: The study participation rate was 39% (564/1,431). Three of 564 participants tested positive for DENV-1 infection (after marginal calibration, 0.41%; 95% confidence interval: 0.00–0.84). The spatial analysis showed that cases were clustered at the household level. Most participants perceived the presence of mosquitos as abundant (83%) and reported frequent mosquito bites (57%). We incidentally identified six past West Nile virus infections (0.9%; 95% CI: 0.2–1.6). Conclusion: This serosurvey confirms the potential for arboviral diseases to cause outbreaks − albeit limited for now − in France and Europe.
Shared medical appointment for early stage melanoma survivorship.
Authors: Pauline Funchain, Jung Min Song, Carolyn Stanek, Michael J. McNamara, Ahmad A. Tarhini, Brian Gastman, Joel Daniel Marcus
Journal: Journal of Clinical Oncology (2018)

69 Background: Shared medical appointments (SMA) are a newer patient care format that involve both education and creation of individualized medical plans for multiple patients in a group setting. SMAs have been found to be cost-effective with high patient satisfaction scores. Methods: We describe an SMA model for early stage melanoma surveillance. The development of our SMA required multidisciplinary input from oncology, psychology, social work, schedulers, business, nursing and cancer center administration. We emphasized creation of a nonjudgmental environment to educate and promote healthy behavior. Results: Our early stage melanoma SMA involves 4-6 patients with an APP as group leader, RN as facilitator, and PsyD to provide psychosocial support. The 90-minute visit starts with a private physical exam followed by group education, activities, and formation of an individualized surveillance plan. An integral component of our SMA is the use of a self-assessment Melanoma Risk tool that has been found to be an efficient method to promote sun protective behaviors. Patients self-identify behavioral risks and personalize strategies to combat long-term effects of unhealthy behaviors. Psychosocial aspects are monitored with the NCCN distress management tool to identify areas of distress. The primary goals of care are to diminish isolation, enhance self-management, and provide professional expertise in combination with first-hand information from peers. Long-term goals are to decrease anxiety and increase survival with prevention. Conclusions: The first project to our knowledge utilizing an SMA format for cancer surveillance, this effort identifies a population at risk and provides education and psychosocial support to change high-risk behaviors. Future areas of research include quantifying outcomes of SMA-based surveillance and the addition of significant others to enhance surveillance.
Analysis of <i>RAS</i>/<i>BRAF</i> mutations in a randomized phase II WJOG6510G study of panitumumab plus irinotecan versus cetuximab plus irinotecan in chemorefractory metastatic colorectal cancer.
Authors: Tomohiro Nishina, Hiroya Taniguchi, Daisuke Sakai, Hisato Kawakami, Naotoshi Sugimoto, Hiroki Hara, Taito Esaki, Tadamichi Denda, Akitaka Makiyama, Masahiro Tsuda, Hiroyuki Okuda, Naoki Izawa, Ayumu Hosokawa, Kentaro Yamazaki, Shinya Tokunaga, Toshikazu Moriwaki, Akihito Tsuji, Yasuhiro Koh, Junji Kishimoto, Kei Muro
Journal: Journal of Clinical Oncology (2018)

624 Background: A randomized phase II WJOG6510G study demonstrated non-inferiority of panitumumab (Pmab) plus irinotecan (IRI) to cetuximab (Cmab) plus IRI in terms of progression-free survival (PFS) in wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC). Here, we performed exploratory analyses of updated survival data using KRAS exon 2 and RAS/BRAF statuses. Methods: In this trial, patients with WT KRAS exon 2 mCRC who progressed after failure of fluoropyrimidine, IRI, and oxaliplatin were randomized to receive Pmab or Cmab in combination with IRI. An independent central laboratory performed RAS/BRAF testing using a PCR-reverse sequence specific oligonucleotide method which can detect 48 types of KRAS/NRAS and 34 types of BRAF mutations. Results: In the ITT population, patient characteristics included the following (Pmab/Cmab): number 61/59; male 69%/63%; median age 64 y/64 y; ECOG PS 0 62%/54%; left-sided primary tumor 85%/88%; multiple sites of metastases 51%/66%. At the time of updated analysis, 113 (94%) and 117 (98%) out of 120 patients had OS and PFS events, respectively. Median PFS was 5.42 months in the Pmab arm and 4.27 months in the Cmab arm (HR 0.674, unstratified log-rank p = 0.035). Median overall survival (OS) was 14.85 months in the Pmab arm and 11.53 months in the Cmab arm (HR 0.675, p = 0.037). In 83 patients, RAS/BRAF tests revealed 19 patients (23%) with RAS and 4 patients (5%) with BRAF mutations (two with V600E, two with non-V600E). Patients with RAS and BRAF mutations did not respond to the treatments. In the RAS WT population, a better PFS trend was observed for Pmab treatment (median 6.06 months vs. 5.26 months, HR 0.629, p = 0.08); however, OS was similar in both arms (median 14.85 months vs. 11.26 months, HR 0.818, p = 0.449). Conclusions: In this analysis, a modest survival benefit was found to be associated with Pmab plus IRI compared to Cmab plus IRI in WT KRAS exon2 mCRC, which warrants further evaluation in the WT RAS population. The number of analytic cases of RAS/BRAF status will be updated in the presentation. Clinical trial information: UMIN000006643.
Utilization of a web-based survivorship and supportive oncology training curriculum for clinicians.
Authors: Frank J. Penedo, Betty Roggenkamp, Carol A. Rosenberg, Julia Rachel Trosman, Patricia A. Robinson, Eileen Knightly, Mary Pasquinelli, Paramjeet Khosla, Anne Bowman, Teresa Lillis, James Gerhart, Megan Slocum, Sofia F. Garcia, Rosa Berardi, Joanna Martin, Shelly S. Lo, Christine B. Weldon
Journal: Journal of Clinical Oncology (2018)

19 Background: A challenge in supportive oncology, integral to patient care, is training the health professional workforce. A collaborative funded by The Coleman Foundation of 30+ clinicians (faculty) from 25 institutions (academic, community &amp; safety net) developed a unique fundamental survivorship care (Weldon JCO 2017) and supportive oncology training curriculum (Trosman JNCCN 2017). Methods: Using data from The National Comprehensive Cancer Network Continuing Education team, we analyzed utilization of survivorship and supportive oncology education courses using simple frequencies. Results: Over 3200 courses were completed (pretest, course, post-test, evaluation) and 4850 accessed. Nurses completed 56%, physicians 15%, social workers/psychologists/support staff 14%, advance practice clinicians 8%, and various roles for the rest. Courses in table. Conclusions: NCCN’s education portal achieved strong utilization from a variety of healthcare professionals in these courses. The Coleman Supportive Oncology Collaborative supports improvement in supportive care with tools, processes and training and will continue to update/offer courses through this portal.[Table: see text]
Resolving the Productivity Paradox of Health Information Technology
Authors: Robert M. Wachter, Michael D. Howell
Journal: JAMA (2018)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Unicancer GI PRODIGE 24/CCTG PA.6 trial: A multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine (gem) in patients with resected pancreatic ductal adenocarcinomas.
Authors: Thierry Conroy, Pascal Hammel, Mohamed Hebbar, Meher Ben Abdelghani, Alice Chia-chi Wei, Jean-Luc Raoul, Laurence Chone, Eric Francois, Pascal Artru, James Joseph Biagi, Thierry Lecomte, Eric Assenat, Roger Faroux, Marc Ychou, Julien Volet, Alain Sauvanet, Claire Jouffroy-Zeller, Patrick Rat, Florence Castan, Jean-Baptiste Bachet
Journal: Journal of Clinical Oncology (2018)

LBA4001 Background: FOLFIRINOX is more effective than gem as first-line treatment in metastatic pancreatic cancer for patients (pts) with good performance status. This trial assessed the benefit of mFOLFIRINOX in the adjuvant setting. Methods: PRODIGE 24/CCTG PA.6 is a phase III multicenter, randomized clinical trial. Pts aged 18-79 years with histologically proven pancreatic ductal adenocarcinomas, 21-84 days after R0 or R1 resection, WHO PS ≤1, adequate hematologic and renal function, and no cardiac ischemia, were eligible. Randomization was stratified by center, pN, R margin status, and post-operative CA 19-9 level (≤ 90 U/mL vs 91-180). Arm A pts received 28-day cycles of gem on days 1, 8, and 15 for 6 cycles. Arm B pts received mFOLFIRINOX (oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 150 mg/m² D1, and 5-FU 2.4 g/m² over 46 h) every 14 days for 12 cycles. Primary endpoint was disease-free survival (DFS). Secondary endpoints were overall survival (OS), metastasis-free survival (MFS), and adverse events (AE). 490 pts were required to observe 342 events to show a gain in 3-year DFS from 17% to 27% (HR = 0.74) with a two-sided α = 0.05 and 80% power. Hazard ratios (HR) and 95% CI were estimated by a stratified Cox proportional hazard model. We observed 91.5% of the events required. The IDMC approved early ITT analysis before March 15, 2018. Surgical procedures, pathology and postoperative CT scans reports were centrally reviewed. Results: From Apr 2012 to Oct 2016, 493 pts were enrolled in 77 centers: Arm A/B: 246/247. With a median follow up of 30.5 months [m] (95% CI, 29.5-33.7), median DFS was 12.8 (95% CI, 11.7-15.2) in Arm A vs 21.6 m (95% CI, 17.5-26.7) in Arm B, HR = 0.59 (95% CI, 0.47-0.74). The median OS (Arm A/B) was 34.8 (95% CI, 28.6-43.8) vs 54.4 m (95% CI, 41.5- --), HR = 0.66 (95% CI, 0.49-0.89). The median MFS (Arm A/B) was 17.7 (95% CI, 14.2-21.7) vs 30.4 m (95% CI, 21.6- --), HR = 0.59 (95% CI, 0.46-0.76). Grade 3-4 AE (Arm A/B) were reported in 51.1% vs 75.5%, including 12% grade 4 in each arm, with a toxic death in Arm A. Conclusion: Adjuvant mFOLFIRINOX is safe and significantly improves DFS, MFS and OS compared to gem. Clinical trial information: NCT01526135.
The association of cardiovascular autonomic dysfunction and the prediction of COPD can be explained by neurohumoral activation
Authors: Stefan Andreas
Journal: European Respiratory Journal (2018)

I read with great interest the recent work by Ricci et al. [1] published in the European Respiratory Journal . This insightful population-based study followed a very large cohort without baseline airflow obstruction for 32 years. Interestingly, baseline orthostatic blood pressure decrease, as well as increased resting heart rate, was associated with reduced lung function during follow-up. The authors consequently suggested that subtle signs of cardiovascular autonomic dysfunction may precede the development of chronic obstructive pulmonary disease (COPD). Clinical markers of subtle cardiovascular autonomic dysfunction predict incident COPD: the potential role of neurohumoral activation <http://ow.ly/mUcW30jMnPC>
Review of Eric Plemons, <i>The Look of a Woman: Facial Feminization Surgery and the Aims of Trans-Medicine</i>
Authors: Cressida J. Heyes
Journal: The American Journal of Bioethics (2018)

"Review of Eric Plemons, The Look of a Woman: Facial Feminization Surgery and the Aims of Trans-Medicine1." The American Journal of Bioethics, 18(6), pp. W1–W2
Radiotherapy and CD40 Activation Separately Augment Immunity to Checkpoint Blockade in Cancer
Authors: Andrew J. Rech, Hannah Dada, Jonathan J. Kotzin, Jorge Henao-Mejia, Andy J. Minn, Christina Twyman-Saint Victor, Robert H. Vonderheide
Journal: Cancer Research (2018)

Immunotherapy in pancreatic ductal adenocarcinoma (PDA) remains a difficult clinical problem despite success in other disease types with immune checkpoint blockade (ICB) and chimeric antigen receptor T-cell therapy. Mechanisms driving immunosuppression and poor T-cell infiltration in PDA are incompletely understood. Here, we use genetically engineered mouse models of PDA that recapitulate hallmarks of human disease to demonstrate that CD40 pathway activation is required for clinical response to radiotherapy and ICB with αCTLA-4 and αPD-1. The combination of an agonist αCD40 antibody, radiotherapy, and dual ICB eradicated irradiated and unirradiated (i.e., abscopal) tumors, generating long-term immunity. Response required T cells and also short-lived myeloid cells and was dependent on the long noncoding RNA myeloid regulator Morrbid Using unbiased random forest machine learning, we built unique, contextual signatures for each therapeutic component, revealing that (i) radiotherapy triggers an early proinflammatory stimulus, ablating existing intratumoral T cells and upregulating MHC class I and CD86 on antigen-presenting cells, (ii) αCD40 causes a systemic and intratumoral reorganization of the myeloid compartment, and (iii) ICB increases intratumoral T-cell infiltration and improves the CD8 T-cell:regulatory T-cell ratio. Thus, αCD40 and radiotherapy nonredundantly augment antitumor immunity in PDA, which is otherwise refractory to ICB, providing a clear rationale for clinical evaluation.Significance: Radiotherapy and αCD40 disrupt key links between innate and adaptive immunity, ameliorating resistance to immune checkpoint blockade in pancreatic cancer via multiple cellular mechanisms. Cancer Res; 78(15); 4282-91. ©2018 AACR.
Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial
Authors: Jorge Cortes, Alexander E Perl, Hartmut Döhner, Hagop Kantarjian, Giovanni Martinelli, Tibor Kovacsovics, Philippe Rousselot, Björn Steffen, Hervé Dombret, Elihu Estey, Stephen Strickland, Jessica K Altman, Claudia D Baldus, Alan Burnett, Alwin Krämer, Nigel Russell, Neil P Shah, Catherine C Smith, Eunice S Wang, Norbert Ifrah, Guy Gammon, Denise Trone, Deborah Lazzaretto, Mark Levis
Journal: The Lancet Oncology (2018)