tbuckley/cabot-search huggingface dataset:
Nivolumab (anti-PD-1, BMS-936558, ONO-4538) in patients (pts) with advanced non-small-cell lung cancer (NSCLC): Survival and clinical activity by subgroup analysis.
Authors: Julie R. Brahmer, Leora Horn, Leena Gandhi, David R. Spigel, Scott Joseph Antonia, Naiyer A. Rizvi, John D. Powderly, Rebecca Suk Heist, Richard D. Carvajal, David Michael Jackman, Lecia V. Sequist, David C. Smith, Philip D. Leming, Suzanne Louise Topalian, F. Stephen Hodi, Mario Sznol, Christopher Harbison, Georgia Kollia, Ashok Kumar Gupta, Scott N. Gettinger
Journal: Journal of Clinical Oncology (2014)

8112^ Background: Nivolumab, a fully human IgG4, PD-1 immune-checkpoint inhibitor antibody, has shown durable clinical activity in a large phase I trial of pts with advanced solid tumors. For NSCLC pts in this trial, we report overall survival (OS) by dose and histology and clinical activity of pt subgroups including PD-L1 tumor status. Methods: Previously treated pts with advanced NSCLC received IV nivolumab (1, 3, or 10 mg/kg) Q2Wk for ≤96 wk with tumor evaluation by RECIST v1.0. Clinical activity by key prognostic factors was assessed. PD-L1 tumor cell membrane expression was measured in archival specimens (n=68) by a Dako immunohistochemistry assay (positive ≥5% tumor cells). Results: Across doses and histologies, NSCLC pts (N=129, 54% with ≥3 prior therapies) hadmedian overall survival (mOS) of 9.2-14.9 mo and 1- and 2-y OS rates of 32-56% and 12-45%, respectively (Table). At the 3 mg/kg dose, mOS was 14.9 mo; 1- and 2-y OS rates were 56% and 45%. Objective response rate was 17% (22/129); median response duration was 17 mo. Clinical activity was observed across all pt subgroups, including <3 and ≥3 prior therapies and with/without EGFR or KRAS mutations. For pts with PD-L1(+) and (–) tumors, mOS was 7.8 mo (95% CI: 5.6, 21.7) and 10.5 mo (5.2, 21.2), respectively; mPFS was 3.6 mo (1.8, 7.5) and 1.8 mo (1.7, 2.3). Grade 3-4 treatment-related adverse events occurred in 14% of pts; most common was fatigue (3%). Conclusions: Nivolumab continues to demonstrate an encouraging survival profile and clinical activity across NSCLC pt subgroups with a manageable safety profile. Ongoing phase III trials are evaluating 3 mg/kg nivolumab in NSCLC pts and PD-L1 as a potential predictor of clinical outcomes. Clinical trial information: NCT00730639. Pts mOS,* mo (95% CI) OS rate,* % (95% CI) [pts at risk] 1-Y 2-Y All† n=129 9.9 (7.8, 12.4) 42 (34, 51) [48] 24 (16, 32) [20] 1 mg/kg n=33 9.2 (5.3, 11.1) 32 (16, 49) [8] 12 (3, 27) [2] 3 mg/kg n=37 14.9 (7.3, NR) 56 (38, 71) [17] 45 (27, 61) [9] 10 mg/kg n=59 9.2 (5.2, 12.4) 40 (27, 52) [23]) 19 (10, 31) [9] Squamous n=54 9.2 (7.3, 12.5) 40 (27, 54) [19] 24 (13, 37) [9] Nonsquamous n=74 10.1 (5.7, 13.7) 43 (32, 54) [28] 23 (13, 34) [10] Abbreviation: NR, not reached. *Sept 2013 analysis. †One pt had unknown histology.
Abstract 16735: Role of the Autonomic Nervous System in Cardioprotection by Remote Ischemic Preconditioning
Authors: Martin Donato, Bruno Buchholz, Ricardo J Gelpi
Journal: Circulation (2011)

The mechanisms underlying remote ischemic preconditioning (r-IPC) have not been fully elucidated. In particular, it is unknown how the cardioprotective signal is transmitted from the preconditioned remote organ to the heart. We hypothesize that r-IPC activates a neural pathway, and that the cardioprotective signal reaches the heart via the vagus nerve, preconditioning the heart through the activation of muscarinic receptors. Our aim was to determine the possible role of the vagus nerve and muscarinic receptors in the mechanisms of r-IPC cardioprotection. Methods: anesthetized rabbits (n=6, r-IPC) were subjected to 3-cycle hind limb ischemia (5 min) and reperfusion (5 min). The hearts were then excised and perfused (Langendorff technique). Myocardial infarction was induced by 30 min of global ischemia followed by 2 h of reperfusion. In the non-r-IPC group (n=5), animals were subjected to a sham operation and then received the same protocol as group 1. Group 3 (r-IPC with vagal section, n=4) received the same protocol as group 2, but the left and right vagus nerves were sectioned before r-IPC. Group 4 (r-IPC with atropine, n=4) received the same protocol as group 2, but atropine was administered during the r-IPC protocol. In group 5 (vagal stimulation, n-4), the right vagus nerve was sectioned and efferently electrically stimulated. Then, the same protocol as in group 1 was performed. Results: In the non-r-IPC group, infarct size was 39.9±4.8%. r-IPC decreased infarct size to 22.7±5.7% (p&lt;0.05). Vagal section and atropine abolished the effect of r-IPC, reaching an infarct size of 53.2±3.5% and 39.8±2.1, respectively (p&lt;0.05). Vagal stimulation decreased infarct size to 18.1±4.7% (p&lt;0.05). Conclusion: r-IPC activates a neural afferent pathway and the cardioprotective signal reaches the heart via the vagus nerve (efferent via). Acetylcholine acting on muscarinic receptors thus activates the IPC phenomenon.
Scientific Foundations of Neurology.
Authors: Macdonald Critchley, James Lee O'Leary, Bryan Jennett
Journal: Annals of Internal Medicine (1973)

editors of this multiauthored volume intended to highlight some of the more recent work [for] neurologic clinicians or research-workers who are anxious for information as to the scientific principles of their own studies or those of colleagues in cognate fields.  book is divided into major sections, Physiology in General, The Peripheral Nervous System, Motor System, Epilepsy, Sensory System, Higher Nervous Activity, Cerebral Circulation, Cerebrospinal Fluid and Intracranial Pressure, Diagnostic and Therapeutic Techniques, and finally, Some Interesting Conditions. Each section has chapters by several authors.  editors make no attempt to coordinate or correlate the contributions. Subjects such as neuroradiology, genetics, and developmental or pediatric neurology receive little attention. How well do the editors meet their goals? As to highlighting recent work for specialists in the field, we must challenge several chapters. For example, in The Nerve Cell and Its Properties, only three of the 21 ref-
Injuries Resulting From Car Surfing—United States, 1990-2008
Authors: Arlene I Greenspan, Ruth A Shults, J Halpin
Journal: JAMA (2008)

This article reports statistics on car-surfing injuries. Car  is a term introduced in the mid-1980s to describe a thrill-seeking activity that involves riding on the exterior of a moving motor vehicle while it is being driven by another person. Because traditional public health datasets do not collect morbidity or mortality data on this practice, the article is based on a search conducted by the Centers for Disease Control and Prevention (CDC) of U.S. newspaper reports that is used to provide an initial characterization of car-surfing injuries on a national scale. The analysis identified 58 reports of car-surfing deaths and 41 reports of nonfatal injury from 1990 through August 2008. Most reports of car-surfing injuries came from newspapers in the Midwest and South (75%), and most of the injuries were among males (70%) and persons aged 15--19 years (69%). Injuries from car-surfing can come from falling off the moving vehicle, falling down onto the vehicle, jumping from the vehicle, or being hit by an object while on top of the moving vehicle. The authors note that the statistics could be underreported, as national injury surveillance systems, trauma registries, and death certificates lack sufficient detail to distinguish car-surfing victims from others who have fallen from a moving motor vehicle. Several behaviors were excluded that closely resemble car surfing but did not fit the case definition, including injuries resulting from a person leaning out of a window or the sunroof of a moving vehicle or being pulled alongside or behind a motor vehicle (typically while on a bike or skateboard). Vehicle speed was less than 30 mph in 11 of the 21 cases where speed was reported (52%), with fatalities occurring at speeds ranging from 5 mph to 80 mph. Alcohol or drugs were mentioned as contributing factors in 11 of 99 cases overall (11%) and six of 58 fatal cases (10%). The article includes three illustrative cases of deaths or serious injury from car-surfing injury. The authors conclude that parents and teens should be aware of the potentially lethal consequences of car surfing, which can occur even at low vehicle speeds, sometimes resulting from unanticipated movements of the vehicle, such as swerving or braking. An editorial comment appended to the article stresses that raised awareness on the part of the public, parents, teens, health care providers and policymakers might lead to better reporting of these activities in traditional public health data sets and allow more accurate calculation of incidence and fatality rates, which might lead to improved prevention efforts.
Complementary medicine (CAM) use among women receiving chemotherapy for ovarian cancer and the potential for interactions with prescribed medication
Authors: S. E. Ferguson, A. Rana, A. Patel, B. Rosen, A. M. Oza, H. Mackay
Journal: Journal of Clinical Oncology (2008)

5576 Background: The use of CAM is common in cancer patients (pts). There is increasing concern about the potential drug interactions between CAM and conventional medications in this population. We sought to evaluate the use of CAM in pts undergoing chemotherapy for ovarian cancer and evaluate the risk of CAM/ conventional medication interactions. Methods: Pts receiving chemotherapy for ovarian cancer completed a survey on all drugs and CAM taken within the previous month. Information on patient attitudes to CAM was also sought. Conventional medication use was confirmed from the patient chart. Drug Interaction Facts software/MEDLINE search and CAM databases were used to screen for potential interactions and to classify them in terms of severity (major, moderate, minor) and level of evidence (LOE) 1 to 5 (1= highest level). Results: 45 women (median age 58, range 26–87) completed the questionnaire. 28 (62%) pts were using CAM: 20 (71%) >1 CAM and 10 (36%) >3. Fourteen (61%, n=23) consulted a friend/relative and 4 (14%) spoke with a physician prior to starting CAM. Nine (36%) informed their oncologist that they were using CAM, despite 90% feeling their oncologist “needed to know”. Ten (36%) believe CAM could have unwanted side effects. 12 (43%) agreed CAM was “perfectly” safe with chemotherapy. Only one (3%) agreed CAM could effect other medications. Among the 28 pts using CAM, 7 potential interactions between CAM and chemotherapy were identified (LOE: 3/4; severity: moderate). The most common CAM found to potentially interact with chemotherapy were ginseng (3pts) and ginkgo (3 pts). A further 7 potential interactions were identified between CAM and non-chemotherapy medications (LOE: 1/4; severity: minor to moderate). The most common conventional medication with potential interaction with CAM was warfarin (5pts, LOE: 3; severity: moderate). Conclusions: A significant proportion of women use CAM during their chemotherapy for ovarian cancer. The majority of them do not discuss the use of CAM with their oncologists. Although data is limited, drug/CAM interactions can potentially impact on patient care. Oncologists need to be aware of this issue and initiate discussion with their patients regarding CAM use during cancer treatment. No significant financial relationships to disclose.
Forensic medicine; courtroom applications to legal principles.
Authors: Lewis J. Siegel
Journal: JAMA (1963)

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
A phase II trial of N-Acetyl-GM3/VSSP vaccine in high-risk resected melanoma patients (pts). Does vaccination modify melanoma outcome after relapse?
Authors: M. A. Castro, G. Cinat, M. Guthmann, M. R. Gabri, D. F. Alonso, L. Fainbom
Journal: Journal of Clinical Oncology (2008)

3026 Background: Quantitative and qualitative changes occur in ganglioside expression during the oncogenic transformation. Cellular over-expression and shedding of gangliosides into the interstitial space may play a central role in cell growth regulation, immune tolerance and tumor-angiogenesis, representing an interesting target for anticancer therapy. Methods: Based on previous phase I study (Bitton et al, PASCO 2002, #1376), 38 high risk melanoma pts received N-Acetyl-GM3/VSSP vaccine in an adjuvant setting. Stage III: 8 pts, local-regional and systemic relapsed pts: 30 pts. All patients had no clinical evidence of disease. Five doses of 360 μg were given IM Q14D, 4 doses Q28D and then Q90D up to 2 years of treatment, relapse or unacceptable toxicity. Clinical outcome, humoral and cellular responses (Ig M anti-GM3, Ig G anti VSSP-GM3 and INFγ anti GM3 detected by Elispot) and toxicity (NCIC v2) were evaluated. Results: At a median follow-up of 35m (r: 7- 62 ), 28 pts (74%) relapsed and 23 (62%) are alive, most of them disease-free. One pt was lost at 7m. Median PFS was 8.5m (r:1–62). Median follow-up for alive pts is 49m (r:7–63).The estimated 5-year OS was 56% (95% CI: 34–76, Kaplan-Meier). Remarkably, many of the pts who relapsed were successfully rescued with local and/or systemic treatments, explaining the important gap between PFS and OS. Although serum reactivity to the vaccine (Ig G anti-VSSP-GM3) was observed in all patients, no specific humoral or cellular responses were detected. Mild to moderate local reactions, transient fever and asthenia were the most frequent toxicities observed. Five patients discontinued vaccination due to adverse events: post-vaccination G3 hypotension plus G3 ASAT/ALAT elevation (2); G2 injection site reaction (2); and syncope with uncertain relation to treatment (1). Conclusions: Compared to published data, observed OS was better than expected. N-Acetyl-GM3/VSSP vaccine might impact on the course of the disease through an antitumor effect or modulating responses to following treatments. The lack of specific immune response is probably due to the low immunogenicity of the ganglioside. Toxicity was acceptable. The immunomodulatory properties of GM3/VSSP warrants further investigation. No significant financial relationships to disclose.
Myocardial Iron overload In Thalassemia Major. how Early To Check?
Authors: Caterina Borgna-Pignatti, Antonella Meloni, Giulia Guerrini, Aldo Filosa, Giovan Battista Ruffo, Tommaso Casini, Nicola Romano, Aurelio Maggio, Elisabetta Chiodi, Vincenzo Positano, Massimo Lombardi, Alessia Pepe
Journal: Blood (2013)
Postnatal depression
Authors: J P Richards, P. Talbot
Journal: BMJ (1998)

Costings were inadequateEditor-Comparing the costs of home and acute hospital care, Coast et al address a subject of intense interest to NHS managers. 1The cost of home care in their study was based on a bottom up analysis, in which use of resources was measured on a patient by patient basis.The cost of hospital care, however, was simply the average cost of inpatient care, which includes the use of operating theatres, etc. Patients for whom both sources of care are a viable option, however, are at the lower end of the intensity range for hospital care.The authors recognise this but address the problem by conducting a sensitivity analysis.They imply that assuming a
Human Parasitology. With Notes on Bacteriology, Mycology, Laboratory Diagnosis, Hematology and Serology.
Authors: Damaso Rivas
Journal: JAMA (1920)

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
Soundings: Surfing the web
Authors: George Dunea
Journal: BMJ (2002)

Look out, doctors! Your patients may know more than you do. For here is a mere fraction of the 60 pages of medical news that I was able to print out on 21 May in less than 10 minutes by surfing the web. It may not all be peer reviewed or evidence based, but here it is anyway.

In Italy they have a “red cell loader” that attaches drug molecules to erythrocytes and returns them to the patient's body, so that therapeutic levels can be maintained for up to seven days. In Sweden there were reports of large doses of carcinogenic acrylamide being found in fried foods, but later frightened readers were reassured that this was neither dangerous nor peer reviewed, that there was much more acrylamide in cigarettes, and that one should go easy on fried foods anyway.

From England comes news that the tongue twister diethylenetriamine pentaacetic acid deprives skin bacteria of iron and keeps armpits smelling fresher than other deodorants. The Prince of Wales wants the government to pay for complementary medicine. In the United States a woman who enjoys acupuncture to calm her nerves had sudden severe pain. “Oh, that hurt you because you have problems there,” explained the acupuncturist, but later an ultrasound showed that there was blood in the peritoneal cavity.

A long article advises doctors on how to deal with the pharmaceutical industry without selling their souls. Another reminds us that aspirin is the oldest wonder drug, that it relieved Enrico Caruso's headaches, and allowed Franz Kafka to write about cockroaches, and how women now can take “Aspirin Plus Calcium.” Yet another article describes how antidepressants normalise serotonin and help control bulimia nervosa.

The Guardian worried about who will pay for all the new expensive cancer cures; and indeed there were stories that day about imatinib for leukaemia, cetuximab for colon cancer, bryostatins made by marine organisms, bevacizumab that inhibits angiogenesis, pemetrexed for mesotheliomas, Iressa for lung cancers, and tiny radioactive seeds that destroy cancers locally.

In Michigan cancer families were offered free accommodation at a cancer centre. But in Singapore children who read more than two books per week are three times more likely to suffer from severe myopia, and therefore I stop now before we all become affected.
Abstract 3740: Natural History and Determinants of Right Ventricular Dysfunction After Acute Pulmonary Embolism Assessed by Strain Rate Echocardiography
Authors: Tudor Poerner, Eric Koletzki, Ines Boehnisch, Bjorn Goebel, Tim Sueselbeck, Martin Borggrefe, Dariusch Haghi
Journal: Circulation (2006)

Aim of the study was to assess global and regional right ventricular (RV) function after acute pulmonary embolism (APE) and to investigate the determinants of acute and chronic right ventricular RV...
How To Do It: Doctor on a mountaineering expedition
Authors: C. H D A'Court, R. H Stables, S. Travis
Journal: BMJ (1995)

of resource allocation and planning models.Such a link is in danger of being lost in a disaggregated NHS, especially with the capacity of fundholding to dilute systematic and equitable resource allocation to populations.Services should also have their capital and revenue requirements funded together; and providers should be accountable for long term plans to health authorities.If this does not happen then long term benefit is lost in short-termism and fragmentation.
Effect of nilotinib on the pharmacokinetics and pharmacodynamics of warfarin
Authors: O. Yin, N. J. Gallagher, D. Fischer, L. Zhao, W. Zhou, G. Golor, H. Schran
Journal: Journal of Clinical Oncology (2009)

7063 Background: Nilotinib, a highly selective and potent BCR-ABL tyrosine kinase inhibitor, is approved for the treatment of CML-CP and CML-AP in patients resistant or intolerant to prior therapy including imatinib. Nilotinib has shown competitive inhibition of CYP2C9 in vitro, but its effect on CYP2C9 activity in human is unknown. This study evaluated the effects of nilotinib on the pharmacokinetics (PK) and pharmacodynamics (PD) of warfarin, a sensitive CYP2C9 substrate, in healthy subjects. Methods: Twenty-four subjects (6F, 18M, age 21–65 years) were enrolled to receive a single oral 25 mg warfarin with either 800 mg nilotinib or matching placebo (administered 30 minutes after consumption of a high-fat meal) in a cross-over design. Serial blood samples were collected post-dose for determining nilotinib, S- and R-warfarin concentrations. Prothrombin time (PT) and international normalized ratio (INR) were determined as PD measures for warfarin. CYP2C9 genotyping was performed in all subjects using TaqMan assay. Results: Sixteen subjects were identified as CYP2C9 extensive metabolizers (EM) and 8 as intermediate metabolizers (IM), but none was poor metabolizer. PK parameters of S- and R-warfarin were found to be similar between two treatments (warfarin + nilotinib versus warfarin alone) for both EM and IM groups. The geometric mean ratios (90% CIs) for the C max and AUC 0-∞ of S-warfarin in all subjects were 0.98 (0.95–1.02) and 1.03 (0.99–1.07), respectively, and for R-warfarin were 1.00 (0.96–1.04) and 1.02 (0.99–1.06) respectively. Mean ratios for the maximum value and AUC of PT were 1.00 (0.96–1.04) and 1.00 (0.98–1.02), respectively, and for INR were 1.00 (0.97–1.01) and 1.00 (0.99–1.01), respectively. Nilotinib C max was 1872±560 ng/mL, which is comparable to the mean steady-state C max in CML and GIST patients receiving 400 mg BID doses. Adverse effects observed following either treatment were generally consistent with the known safety profiles of both drugs, and there were no new safety issues observed. Conclusion: The study results demonstrate a lack of effect of nilotinib on the PK and PD of warfarin, suggesting nilotinib does not inhibit CYP2C9 activity in human subjects. These findings suggest that warfarin can be used with nilotinib concurrently without the risk of bleeding. [Table: see text]