tbuckley/cabot-search huggingface dataset:
Ethics and the Legalization of Physician-Assisted Suicide
Authors: Timothy L. Gieseke
Journal: Annals of Internal Medicine (2018)

Letters5 June 2018Ethics and the Legalization of Physician-Assisted SuicideTimothy L. Gieseke, MDTimothy L. Gieseke, MDUniversity of California, San Francisco, San Francisco, California (T.L.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0081 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Sulmasy and colleagues' (1) position paper discusses PAS. I live in California, where we now have a law similar to Oregon's that gives our patients this option. In California, patients, families, and the medical community have a wide range of opinions on this emotionally charged subject. I appreciate the ACP's review of the ethical issues for providers to consider as they decide whether to support or refer requests for PAS.I have been a hospice medical director and am committed to high-quality palliative care for medically complex, fragile persons living in postacute and long-term care settings. Death ...Reference1. Snyder L, Mueller PS; Ethics, Professionalism and Human Rights Committee of the American College of Physicians. Ethics and the legalization of physician-assisted suicide: an American College of Physicians position paper. Ann Intern Med. 2017;167:576-8. [PMID: 28975242]. doi:10.7326/M17-0938 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: University of California, San Francisco, San Francisco, California (T.L.G.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L18-0081. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEthics and the Legalization of Physician-Assisted Suicide: An American College of Physicians Position Paper Lois Snyder Sulmasy , Paul S. Mueller , and Ethics and the Legalization of Physician-Assisted Suicide Allen H. Roberts II Ethics and the Legalization of Physician-Assisted Suicide Lois Snyder Sulmasy and Paul S. Mueller Ethics and the Legalization of Physician-Assisted Suicide E. Wesley Ely Ethics and the Legalization of Physician-Assisted Suicide Banu E. Symington Ethics and the Legalization of Physician-Assisted Suicide Christie Reimer Metrics 5 June 2018Volume 168, Issue 11Page: 834KeywordsConflicts of interestDisclosureEmotionsLong-term carePalliative carePeriodic acid SchiffSuicide ePublished: 5 June 2018 Issue Published: 5 June 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Identification of biomarkers for TAS-102 efficacy in metastatic colorectal cancer patients based on preclinical analysis and clinical validation.
Authors: Mitsukuni Suenaga, Tetsuo Mashima, Naomi Kawata, Shingo Dan, Takeru Wakatsuki, Eiji Shinozaki, Takashi Ichimura, Mariko Ogura, Daisuke Takahari, Hiroki Osumi, Yumiko Ota, Keisho Chin, Hiroyuki Seimiya, Kensei Yamaguchi, Toshiharu Yamaguchi
Journal: Journal of Clinical Oncology (2018)

669 Background: Trifluridine (FTD) incorporation into DNA is the main anti-tumor mechanism of action of TAS-102. We performed preclinical analysis and translational validation study to identify the candidate cytokines for TAS-102 efficacy in metastatic colorectal cancer (mCRC) patients (pts). Methods: As a first preclinical process, we selected candidate cytokines according to our transcriptomic and cell biological analysis. We then validated predictive value of the cytokines in mCRC pts receiving TAS-102 (discovery) and regorafenib (control). Blood samples were obtained at baseline (BL), before second cycle (2 nd ) and progressive disease (PD), and cytokine levels were measured using ELISA. The change patterns were defined as ‘increased’ or ‘decreased’ from BL. Results: 93 pts were included in this study: 67 received TAS-102 and 26 received regorafenib. Preclinical cDNA microarray analysis with colon cancer cell lines demonstrated marked changes in the RNA expression of interleukin-8, VEGF-A and epiregulin (EREG) after FTD treatment. Particularly, in preclinical model, EREG secretion was highly measured after FTD treatment in FTD-sensitive cells, while not in FTD-resistant cells. In the discovery cohort, increased EREG levels at 2 nd showed trend toward longer PFS and OS than decreased changes (2.6 vs 2.3 mos, P= 0.096; 10.8 vs 6.2 mos, P= 0.091). Meanwhile, decreased EREG levels at PD were marginally associated with longer PFS and significantly with longer OS than increased (4.0 vs 2.3 mos, P= 0.130; 9.8 vs. 6.2 mos, P= 0.016). Combined analysis of EREG changes showed that pts with either increased at 2 nd or decreased at PD had significantly longer PFS and OS compared to those with both decreased at 2 nd and increased at PD (3.0 vs 2.0 mos, HR: 0.47, 95%CI: 0.24-0.93, P= 0.031; 10.8 vs 5.3 mos, HR: 0.30, 95%CI: 0.14-0.61, P= 0.001). The findings were confirmed in the multivariate analysis for OS (HR: 0.311, 95%CI: 0.15-0.66, P= 0.002), and no significant differences were observed in the control cohort. Conclusions: Our preclinical data-based translational validation study suggests that serum EREG levels may predict clinical outcome in mCRC pts receiving TAS-102.
The impact of chemotherapy sequence on survival in node-positive invasive lobular carcinoma.
Authors: Nina Prabha Tamirisa, Hannah Vernia, Samantha M. Thomas, Kelly E. Westbrook, Rachel Adams Greenup, Jennifer Kay Plichta, Laura Horst Rosenberger, Terry Hyslop, Eun-Sil Shelley Hwang, Oluwadamilola Motunrayo Fayanju
Journal: Journal of Clinical Oncology (2018)

587 Background: Breast cancer patients with invasive lobular carcinoma (ILC) have lower rates of downstaging after neoadjuvant chemotherapy (NACT) than those with invasive ductal carcinoma; however, similar criteria – including lymph node involvement – are used to determine administration of NACT in both subtypes. We sought to determine the impact of chemotherapy sequence on survival among node-positive (cN+) ILC patients receiving systemic therapy. Methods: We identified cN1-3 ILC patients in the National Cancer Data Base (2004-2014) who received chemotherapy and divided them into neoadjuvant and adjuvant cohorts. Unadjusted overall survival (OS) was estimated using the Kaplan-Meier method, and differences between groups were tested using the log-rank test. Cox proportional hazards modeling was used to estimate the effect of chemotherapy timing on OS after adjustment for known covariates. Results: 75.7% (n = 17,957) of patients with cN+ ILC (n = 23,736) received chemotherapy; 7,609 (42.3%, median age 54, IQR 47-63) received NACT and 10,348 (57.6%, median age 58, IQR 49-66) received adjuvant chemotherapy. In both cohorts, most patients had grade 2 (NACT 50.1% vs adjuvant 54.2%), ER+ (NACT 86.6% vs adjuvant 92.3%), HER2- (NACT 80.6% vs adjuvant 87.6%) disease. NACT patients had higher rates of cT4 disease vs adjuvant patients (17.4% vs 2.3%, p < 0.001). Unadjusted 5-year OS was worse for NACT patients vs those receiving adjuvant chemotherapy (73.6% vs 83.1%, log-rank p < 0.001). In multivariate analysis, NACT continued to be associated with worse OS (HR 1.33, 95% CI 1.21-1.46). Improved OS was associated with age < 50 (HR 0.82, 95% CI 0.75-0.91), receipt of endocrine therapy (HR 0.60, 95% CI 0.53-0.68), and receipt of radiation therapy (HR 0.81, 95% CI 0.73-0.90). Worse OS was associated with ER- status (HR 1.22, 95% CI 1.03-1.44), PR- status (HR 1.55, 95% CI 1.39-1.72), cT4 stage (HR 2.09, 95% CI 1.76-2.47), and receipt of mastectomy (HR 1.30, 95% CI 1.15-1.45). Conclusions: Among node-positive ILC patients, receipt of NACT is associated with worse survival compared with receipt of adjuvant chemotherapy. These findings suggest that use of NACT in node-positive ILC may be of limited benefit and should be used judiciously.
Using effective web-based tools to address cancer health care disparities.
Authors: Lloyd Devassy Panjikaran, Aju Mathew
Journal: Journal of Clinical Oncology (2018)

76 Background: Most of the World’s cancer patients live in non-English speaking world. However, there is a lack of authentic web-based cancer informational tools in non-English language, especially in low and middle-income countries. With increasing access to internet, there is an emergent need to democratize health information in native languages. The senior author was sensitive to this unmet need and created a comprehensive cancer website in Malayalam, a language spoken by more than 35 million people (www.keralacancercare.com). We describe the steps in creating the web resource and provide data on its use across various web and social media platforms. Methods: The senior author produced educational video sessions and cancer literature in Malayalam language. The website had three main sections – cancer basics, cancer A-Z and cancer FAQs. Cancer basics section contained sections on various basic cancer information such as types of malignancies, definitions, staging, symptoms, risk factors, diagnostic tests and screening. It also included sections on various treatment modalities, treatment side effects and information on cancer risk reduction, genetics and prevention. Cancer A-Z section contained instructional videos on major cancers. Cancer FAQs addressed common cancer myths and questions. A social media profile along with contact information through email service was also launched. The total cost incurred for development of such a web-based tool with presence on social media was less than USD 1500. Results: Since the launch of the web resource in May 2017, the website has now been accessed by more than 5000 unique visitors from 84 countries. More than 50 cancer related questions have been addressed since the launch. The web views of some of the brief informational videos such as ‘how to reduce risk for cancer’ has been viewed more than 150,000 times in social media pages. Conclusions: Creating authentic cancer informational web-based tools will have an immediate impact on addressing cancer healthcare disparities around the world. National and regional cancer societies must foster and encourage creation of novel healthcare informational tools that can truly democratize and empower people.
Endocrine Adjuvant Therapy for Localized Breast Cancer
Authors: Marc E. Lippman
Journal: New England Journal of Medicine (2018)

Investigators now report in the Journal the updated results of two critical trials of endocrine therapy in early-stage breast cancer — SOFT (Suppression of Ovarian Function Trial) and TEXT (Tamoxifen and Exemestane Trial) — with overlapping groups that permitted a combined analysis.1 As in many other endocrine-therapy trials, the effects were not apparent in earlier analyses, but after 8 to 9 years of follow-up, the results are clear. In premenopausal women, the addition of ovarian suppression to tamoxifen was more effective in increasing disease-free survival than tamoxifen alone, and the addition of the aromatase inhibitor exemestane to ovarian suppression was . . .
Mild Traumatic Brain Injury
Authors: Mary Iaccarino
Journal: JAMA Network Open (2018)

Seth A. Seabury, PhD; Étienne Gaudette, PhD; Dana P. Goldman, PhD; Amy J. Markowitz, JD; Jordan Brooks, BA; Michael A. McCrea, PhD; David O. Okonkwo, MD, PhD; Geoffrey T. Manley, MD, PhD; and the TRACK-TBI Investigators; Opeolu Adeoye, MD; Neeraj Badjatia, MD; Kim Boase, BA; Yelena Bodien, PhD; M. Ross Bullock, MD, PhD; Randall Chesnut, MD; John D. Corrigan, PhD; Karen Crawford, MLIS; Ramon Diaz-Arrastia, MD, PhD; Sureyya Dikmen, PhD; Ann-Christine Duhaime, MD; Richard Ellenbogen, MD; V. Ramana Feeser, MD; Adam Ferguson, PhD; Brandon Foreman, MD; Raquel Gardner, MD; Joseph Giacino, PhD; Luis Gonzalez; Shankar Gopinath, MD; Rao Gullapalli, PhD; J. Claude Hemphill, MD; Gillian Hotz, PhD; Sonia Jain, PhD; Frederick Korley, MD, PhD; Joel Kramer, PsyD; Natalie Kreitzer, MD; Harvey Levin, MD; Chris Lindsell, PhD; Joan Machamer, MA; Christopher Madden, MD; Alastair Martin, PhD; Thomas McAllister, MD; Randall Merchant, PhD; Pratik Mukherjee, MD, PhD; Lindsay Nelson, PhD; Florence Noel, PhD; Eva Palacios, PhD; Daniel Perl, MD; Ava Puccio, PhD; Miri Rabinowitz, PhD; Claudia Robertson, MD; Jonathan Rosand, MD, MSc; Angelle Sander, PhD; Gabriella Satris, MSc; David Schnyer, PhD; Mark Sherer, PhD; Murray Stein, MD, MPH; Sabrina Taylor, PhD; Nancy Temkin, PhD; Arthur Toga, PhD; Alex Valadka, MD; Mary Vassar, RN, MS; Paul Vespa, MD; Kevin Wang, PhD; John Yue, BA; Esther Yuh, MD, PhD; Ross Zafonte, DO
Wait Time for Hip Fracture Surgery and Mortality
Authors: Eriko Okada, Koichi Inukai, Hiromichi Aoyama
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 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
Unintended Consequences: Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia
Authors: Liam Byrne, Nchafatso G. Obonyo, Sara D. Diab, Kimble R. Dunster, Margaret R. Passmore, Ai-Ching Boon, Louise See Hoe, Sanne Pedersen, Mohd Hashairi Fauzi, Leticia Pretti Pimenta, Frank Van Haren, Christopher M. Anstey, Louise Cullen, John-Paul Tung, Kiran Shekar, Kathryn Maitland, John F. Fraser
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Fluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question.Objectives: In this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia.Methods: Endotoxemic shock was induced in 16 sheep, after which they received fluid resuscitation with 40 ml/kg of 0.9% saline or commenced hemodynamic support with protocolized noradrenaline and vasopressin. Microdialysis catheters were inserted into the arterial circulation, heart, brain, kidney, and liver to monitor local metabolism. Blood samples were recovered to measure serum inflammatory cytokines, creatinine, troponin, atrial natriuretic peptide, brain natriuretic peptide, and hyaluronan. All animals were monitored and supported for 12 hours after fluid resuscitation.Measurements and Main Results: After resuscitation, animals that received fluid resuscitation required significantly more noradrenaline to maintain the same mean arterial pressure in the subsequent 12 hours (68.9 mg vs. 39.6 mg; P = 0.04). Serum cytokines were similar between groups. Atrial natriuretic peptide increased significantly after fluid resuscitation compared with that observed in animals managed without fluid resuscitation (335 ng/ml [256–382] vs. 233 ng/ml [144–292]; P = 0.04). Cross-sectional time-series analysis showed that the rate of increase of the glycocalyx glycosaminoglycan hyaluronan was greater in the fluid-resuscitated group over the course of the study (P = 0.02).Conclusions: Fluid resuscitation resulted in a paradoxical increase in vasopressor requirement. Additionally, it did not result in improvements in any of the measured microcirculatory- or organ-specific markers measured. The increase in vasopressor requirement may have been due to endothelial/glycocalyx damage secondary to atrial natriuretic peptide–mediated glycocalyx shedding.
Genetic variation in the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway affects contact hypersensitivity responses
Authors: Julien M.D. Legrand, Edwige Roy, Batoul Baz, Pamela Mukhopadhyay, Ho Yi Wong, Ramesh Ram, Grant Morahan, Graeme Walker, Kiarash Khosrotehrani
Journal: Journal of Allergy and Clinical Immunology (2018)
Conservative versus liberal oxygenation targets in critically ill children: the randomised multiple-centre pilot Oxy-PICU trial
Authors: Mark J. Peters, Gareth A. L. Jones, Daisy Wiley, Jerome Wulff, Padmanabhan Ramnarayan, Samiran Ray, David Inwald, Michael Grocott, Michael Griksaitis, John Pappachan, Lauran O’Neill, Simon Eaton, Paul R. Mouncey, David A. Harrison, Kathryn M. Rowan
Journal: Intensive Care Medicine (2018)
Durable Remissions with Ivosidenib in<i>IDH1</i>-Mutated Relapsed or Refractory AML
Authors: Courtney D. DiNardo, Eytan M. Stein, Stéphane de Botton, Gail J. Roboz, Jessica K. Altman, Alice S. Mims, Ronan Swords, Robert H. Collins, Gabriel N. Mannis, Daniel A. Pollyea, Will Donnellan, Amir T. Fathi, Arnaud Pigneux, Harry P. Erba, Gabrielle T. Prince, Anthony S. Stein, Geoffrey L. Uy, James M. Foran, Elie Traer, Robert K. Stuart, Martha L. Arellano, James L. Slack, Mikkael A. Sekeres, Christophe Willekens, Sung Choe, Hongfang Wang, Vickie Zhang, Katharine E. Yen, Stephanie M. Kapsalis, Hua Yang, David Dai, Bin Fan, Meredith Goldwasser, Hua Liu, Sam Agresta, Bin Wu, Eyal C. Attar, Martin S. Tallman, Richard M. Stone, Hagop M. Kantarjian
Journal: New England Journal of Medicine (2018)

Mutations in the gene encoding isocitrate dehydrogenase 1 ( IDH1) occur in 6 to 10% of patients with acute myeloid leukemia (AML). Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of mutant IDH1.We conducted a phase 1 dose-escalation and dose-expansion study of ivosidenib monotherapy in IDH1-mutated AML. Safety and efficacy were assessed in all treated patients. The primary efficacy population included patients with relapsed or refractory AML receiving 500 mg of ivosidenib daily with at least 6 months of follow-up.Overall, 258 patients received ivosidenib and had safety outcomes assessed. Among patients with relapsed or refractory AML (179 patients), treatment-related adverse events of grade 3 or higher that occurred in at least 3 patients were prolongation of the QT interval (in 7.8% of the patients), the IDH differentiation syndrome (in 3.9%), anemia (in 2.2%), thrombocytopenia or a decrease in the platelet count (in 3.4%), and leukocytosis (in 1.7%). In the primary efficacy population (125 patients), the rate of complete remission or complete remission with partial hematologic recovery was 30.4% (95% confidence interval [CI], 22.5 to 39.3), the rate of complete remission was 21.6% (95% CI, 14.7 to 29.8), and the overall response rate was 41.6% (95% CI, 32.9 to 50.8). The median durations of these responses were 8.2 months (95% CI, 5.5 to 12.0), 9.3 months (95% CI, 5.6 to 18.3), and 6.5 months (95% CI, 4.6 to 9.3), respectively. Transfusion independence was attained in 29 of 84 patients (35%), and patients who had a response had fewer infections and febrile neutropenia episodes than those who did not have a response. Among 34 patients who had a complete remission or complete remission with partial hematologic recovery, 7 (21%) had no residual detectable IDH1 mutations on digital polymerase-chain-reaction assay. No preexisting co-occurring single gene mutation predicted clinical response or resistance to treatment.In patients with advanced IDH1-mutated relapsed or refractory AML, ivosidenib at a dose of 500 mg daily was associated with a low frequency of grade 3 or higher treatment-related adverse events and with transfusion independence, durable remissions, and molecular remissions in some patients with complete remission. (Funded by Agios Pharmaceuticals; ClinicalTrials.gov number, NCT02074839 .).
Elucidating the endocrine therapy experience of South Carolina breast cancer survivors.
Authors: Julie Summey Bedi, Elizabeth Charron, Regina A. Franco, Matt Olinger, Lori Dickes, Rachel Mayo
Journal: Journal of Clinical Oncology (2018)

186 Background: Literature consistently shows high discontinuation and non-adherence rates for patients taking endocrine therapy (ET) for breast cancer treatment. The aim of this study is to understand from the breast cancer survivor perspective which modifiable aspects have the greatest impact on the likelihood of ET continuation. Methods: Twenty-two hormone receptor-positive breast cancer survivors under age 64 who had been prescribed ET since 2000 were recruited for participation in focus groups conducted in four South Carolina locations. Qualitative data analysis was completed by a three-member team using an inductive narrative approach. Themes were examined by participant decision to continue or discontinue ET. Results: Participants’ conversations centered around a quality of life cost-benefit analysis that they felt was unique to the individual and could not be generalized by providers. Main themes included the significance of the patient/provider relationship, the desire for a more holistic approach to care, and the need for affirmation in the decision to take ET (i.e. through breast cancer social network, family, faith, research). There was clear support for the utility of multidisciplinary cancer care teams. The roles of nurse navigator and rural pharmacist were specifically highlighted. Participants expressed concerns regarding ET’s damage to their bodies, and participants discussed the dilemma of not having enough time to spend caring for self. Conclusions: The few studies that have addressed currently used interventions to improve adherence showed little to no improvement over usual care. It is imperative that research be conducted that employs a patient-centered perspective. Knowledge gained through further study exploring patient concerns, multidisciplinary teams, and holistic care are needed. There is also a need for novel patient-centered interventions in research to improve compliance and enhance the ET experience for breast cancer survivors.