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Marilyn Kendall, Eileen Cowey, Gillian Mead, Mark Barber, Christine McAlpine, David J Stott, Kirsty Boyd, Scott A Murray
BACKGROUND: Case fatality after total anterior circulation stroke is high. Our objective was to describe the experiences and needs of patients and caregivers, and to explore whether, and how, palliative care should be integrated into stroke care. METHODS: From 3 stroke services in Scotland, we recruited a purposive sample of people with total anterior circulation stroke, and conducted serial, qualitative interviews with them and their informal and professional caregivers at 6 weeks, 6 months and 1 year...
March 5, 2018: CMAJ: Canadian Medical Association Journal, Journal de L'Association Medicale Canadienne
Sigrun Hallmeyer, Rene Gonzalez, David H Lawson, Lee D Cranmer, Gerald P Linette, Igor Puzanov, Bret Taback, C Lance Cowey, Antoni Ribas, Gregory A Daniels, Timothy Moore, Geoffrey T Gibney, Hussein Tawbi, Eric Whitman, Geraldine Lee, Yong Mun, Shiyao Liu, Omid Hamid
BRAF mutations are found in ~50% of metastatic melanomas, most commonly in codon V600. Vemurafenib improves progression-free survival and overall survival in patients with advanced BRAF-mutated melanoma. The results of a descriptive study evaluating vemurafenib in patients with advanced melanoma harbouring BRAF mutations other than V600E are reported. Eligible patients with stage IIIC or IV melanoma and non-V600E BRAF mutations received vemurafenib (960 mg, twice daily). End points included investigator-assessed best overall response rate (primary), time to response, duration of response, progression-free survival, overall survival and safety...
December 2017: Melanoma Research
Raghad M Abdul-Karim, C Lance Cowey
The last several years have seen a dramatic rise in the number of effective therapies that have been shown to improve survival outcomes for patients with advanced melanoma. Among these treatments are the immune checkpoint inhibitors, a new class of immunotherapy, that have demonstrated the ability to improve both response rates and survival outcomes. Pembrolizumab, an immune checkpoint inhibitor that blocks the negative regulatory PD-1 receptor on T-cell lymphocytes, has shown improved efficacy compared to standard therapies with an acceptable tolerability profile...
2017: Cancer Management and Research
Jeffrey Weber, Mario Mandala, Michele Del Vecchio, Helen J Gogas, Ana M Arance, C Lance Cowey, Stéphane Dalle, Michael Schenker, Vanna Chiarion-Sileni, Ivan Marquez-Rodas, Jean-Jacques Grob, Marcus O Butler, Mark R Middleton, Michele Maio, Victoria Atkinson, Paola Queirolo, Rene Gonzalez, Ragini R Kudchadkar, Michael Smylie, Nicolas Meyer, Laurent Mortier, Michael B Atkins, Georgina V Long, Shailender Bhatia, Celeste Lebbé, Piotr Rutkowski, Kenji Yokota, Naoya Yamazaki, Tae M Kim, Veerle de Pril, Javier Sabater, Anila Qureshi, James Larkin, Paolo A Ascierto
BACKGROUND: Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma. METHODS: In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients (≥15 years of age) who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients)...
November 9, 2017: New England Journal of Medicine
Jedd D Wolchok, Vanna Chiarion-Sileni, Rene Gonzalez, Piotr Rutkowski, Jean-Jacques Grob, C Lance Cowey, Christopher D Lao, John Wagstaff, Dirk Schadendorf, Pier F Ferrucci, Michael Smylie, Reinhard Dummer, Andrew Hill, David Hogg, John Haanen, Matteo S Carlino, Oliver Bechter, Michele Maio, Ivan Marquez-Rodas, Massimo Guidoboni, Grant McArthur, Celeste Lebbé, Paolo A Ascierto, Georgina V Long, Jonathan Cebon, Jeffrey Sosman, Michael A Postow, Margaret K Callahan, Dana Walker, Linda Rollin, Rafia Bhore, F Stephen Hodi, James Larkin
BACKGROUND: Nivolumab combined with ipilimumab resulted in longer progression-free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma. We now report 3-year overall survival outcomes in this trial. METHODS: We randomly assigned, in a 1:1:1 ratio, patients with previously untreated advanced melanoma to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo, until progression, the occurrence of unacceptable toxic effects, or withdrawal of consent...
October 5, 2017: New England Journal of Medicine
Dirk Schadendorf, Jedd D Wolchok, F Stephen Hodi, Vanna Chiarion-Sileni, Rene Gonzalez, Piotr Rutkowski, Jean-Jacques Grob, C Lance Cowey, Christopher D Lao, Jason Chesney, Caroline Robert, Kenneth Grossmann, David McDermott, Dana Walker, Rafia Bhore, James Larkin, Michael A Postow
Purpose Approximately 40% of patients with advanced melanoma who received nivolumab combined with ipilimumab in clinical trials discontinued treatment because of adverse events (AEs). We conducted a retrospective analysis to assess the efficacy and safety of nivolumab plus ipilimumab in patients who discontinued treatment because of AEs. Methods Data were pooled from phase II and III trials of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, every 3 weeks for four doses, followed by nivolumab monotherapy 3 mg/kg every 2 weeks (N = 409)...
December 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Dirk Schadendorf, James Larkin, Jedd Wolchok, F Stephen Hodi, Vanna Chiarion-Sileni, Rene Gonzalez, Piotr Rutkowski, Jean-Jacques Grob, C Lance Cowey, Christopher Lao, John Wagstaff, Margaret K Callahan, Michael A Postow, Michael Smylie, Pier Francesco Ferrucci, Reinhard Dummer, Andrew Hill, Fiona Taylor, Javier Sabater, Dana Walker, Srividya Kotapati, Amy Abernethy, Georgina V Long
BACKGROUND: Nivolumab, a monoclonal antibody of immune checkpoint programmed death 1 on T cells (PD-1), combined with ipilimumab, an immune checkpoint cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, as combination therapy on the one hand and nivolumab as monotherapy on the other, have both demonstrated improved efficacy compared with ipilimumab alone in the CheckMate 067 study. However, the combination resulted in a higher frequency of grade 3/4 adverse events (AEs), which could result in diminished health-related quality of life (HRQoL)...
September 2017: European Journal of Cancer
C Lance Cowey, Lisa Mahnke, Janet Espirito, Christoph Helwig, Dina Oksen, Murtuza Bharmal
AIM: This retrospective study of patients in the USA with metastatic Merkel cell carcinoma (mMCC) aimed to assess patient responses to second-line and later (2L+) and first-line (1L) chemotherapy. PATIENTS & METHODS: Out of 686 patients with MCC identified in The US Oncology Network, 20 and 67 patients with mMCC qualified for the 2L+ and 1L study, respectively; the primary analysis population was restricted to immunocompetent patients. RESULTS: In the 2L+ primary analysis population, objective response rate (ORR) was 28...
August 2017: Future Oncology
Shaveta Mulla, Susan Stirling, Sarah Cowey, Rosie Close, Sara Pullan, Rosalind Howe, Lynne Radbone, Paul Clarke
OBJECTIVE: To compare in two epochs of differing phosphate provision serum calcium, phosphate, potassium, and sodium concentrations and the frequency of abnormality of these electrolytes and of sepsis in preterm infants who received an optimised higher amino acid-content formulation. DESIGN AND SETTING: Retrospective cohort study at a single tertiary-level neonatal unit. PATIENTS: Preterm infants given parenteral nutrition (PN) in the first postnatal week during two discrete 6-month epochs in 2013-2014...
September 2017: Archives of Disease in Childhood. Fetal and Neonatal Edition
C L Cowey, L Mahnke, J Espirito, P Fox, C Helwig, D Oksen, M Bharmal
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Anne Rowat, Alex Pollock, Bridget St George, Eileen Cowey, Joanne Booth, Maggie Lawrence
AIM: To determine the top 10 research priorities specific to stroke nursing. BACKGROUND: It is important that stroke nurses build their research capability and capacity. This project built on a previous James Lind Alliance prioritization project, which established the shared stroke research priorities of stroke survivors, carers and health professionals. DESIGN: Research priority setting project using James Lind Alliance methods; a survey for interim prioritization and a consensus meeting for final priority setting...
November 2016: Journal of Advanced Nursing
Lijo John, C Lance Cowey
For decades, no cancer therapy had been shown to improve average survival in metastatic melanoma. Two critical events have occurred, the discovery of melanoma driver mutation subsets and the discovery of immune checkpoint inhibitors, which have allowed for the development of modern, effective therapies. These findings have facilitated a rapid emergence of novel therapeutics for the disease with multiple FDA approvals in the last several years. The drugs vemurafenib, trametinib, and dabrafenib, which inhibit the commonly mutated BRAF pathway, have been approved based on improvements in survival outcomes...
September 2015: Dermatology and Therapy
Simiao Wu, Mansur A Kutlubaev, Ho-Yan Y Chun, Eileen Cowey, Alex Pollock, Malcolm R Macleod, Martin Dennis, Elizabeth Keane, Michael Sharpe, Gillian E Mead
BACKGROUND: Post-stroke fatigue (PSF) is a common and distressing problem after stroke. The best ways to prevent or treat PSF are uncertain. Several different interventions can be argued to have a rational basis. OBJECTIVES: To determine whether, among people with stroke, any intervention reduces the proportion of people with fatigue, fatigue severity, or both; and to determine the effect of intervention on health-related quality of life, disability, dependency and death, and whether such intervention is cost effective...
July 2, 2015: Cochrane Database of Systematic Reviews
Patricia M LoRusso, Scott A Boerner, Mary Jo Pilat, Karen M Forman, Clarice Y Zuccaro, Jeffrey A Kiefer, Winnie S Liang, Sally Hunsberger, Bruce G Redman, Svetomir N Markovic, Aleksandar Sekulic, Alan H Bryce, Richard W Joseph, C Lance Cowey, Leslie Anne Fecher, Jeffrey Alan Sosman, Paul B Chapman, Gary K Schwartz, David W Craig, John D Carpten, Jeffrey M Trent
Targeted therapies and immunotherapies have led to significant improvements in the treatment of advanced cancers, including metastatic melanoma. However, new strategies are desperately needed to overcome therapeutic resistance to these agents, as well as to identify effective treatment approaches for cancer patients that fall outside major targetable mutational subtypes (e.g., non-V600 BRAF melanoma). One such strategy is to extend the paradigm of individually tailored, molecularly targeted therapy into a broader spectrum of melanoma patients, particularly those bearing tumors without commonly recognized therapeutic targets, as well as having failed or were ineligible for immunotherapy...
August 2015: Molecular Cancer Therapeutics
James Larkin, Vanna Chiarion-Sileni, Rene Gonzalez, Jean Jacques Grob, C Lance Cowey, Christopher D Lao, Dirk Schadendorf, Reinhard Dummer, Michael Smylie, Piotr Rutkowski, Pier F Ferrucci, Andrew Hill, John Wagstaff, Matteo S Carlino, John B Haanen, Michele Maio, Ivan Marquez-Rodas, Grant A McArthur, Paolo A Ascierto, Georgina V Long, Margaret K Callahan, Michael A Postow, Kenneth Grossmann, Mario Sznol, Brigitte Dreno, Lars Bastholt, Arvin Yang, Linda M Rollin, Christine Horak, F Stephen Hodi, Jedd D Wolchok
BACKGROUND: Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma. METHODS: We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone...
July 2, 2015: New England Journal of Medicine
Devin B Terhune, Elizabeth Murray, Jamie Near, Charlotte J Stagg, Alan Cowey, Roi Cohen Kadosh
Phosphenes are illusory visual percepts produced by the application of transcranial magnetic stimulation to occipital cortex. Phosphene thresholds, the minimum stimulation intensity required to reliably produce phosphenes, are widely used as an index of cortical excitability. However, the neural basis of phosphene thresholds and their relationship to individual differences in visual cognition are poorly understood. Here, we investigated the neurochemical basis of phosphene perception by measuring basal GABA and glutamate levels in primary visual cortex using magnetic resonance spectroscopy...
November 2015: Cerebral Cortex
Eileen Cowey, Lorraine N Smith, David J Stott, Christine H McAlpine, Gillian E Mead, Mark Barber, Matthew Walters
BACKGROUND: Death after stroke is common, but little is known about end-of-life care processes in acute stroke units. AIM: (1) To identify family and health-care worker perceptions of an end-of-life care pathway for patients who die after acute stroke. (2) To determine whether patients with fatal stroke judged to require an end-of-life care pathway differ from patients with fatal stroke who die without introduction of such a pathway. DESIGN: Mixed methods study integrating qualitative semistructured interviews with quantitative casenote review...
March 2015: Palliative Medicine
R E Passingham, A Chung, B Goparaju, A Cowey, L M Vaina
Humans have a sophisticated knowledge of the actions that can be performed with objects. In an fMRI study we tried to establish whether this depends on areas that are homologous with the inferior parietal cortex (area PFG) in macaque monkeys. Cells have been described in area PFG that discharge differentially depending upon whether the observer sees an object being brought to the mouth or put in a container. In our study the observers saw videos in which the use of different objects was demonstrated in pantomime; and after viewing the videos, the subject had to pick the object that was appropriate to the pantomime...
September 25, 2014: Brain Research
Sara D Robinson, Joyce A O'Shaughnessy, C Lance Cowey, Kartik Konduri
Somatic BRAF mutations have been reported in 1-4% of non-small cell lung cancer (NSCLC), primarily in adenocarcinomas with the BRAF (V600E) mutation in about 50% of the cases. The role of BRAF mutation in NSCLC and the treatment for tumors with such mutations is still evolving. Our patient had metastatic NSCLC with metastases to her brain. Due to the BRAF (V600E) mutation in her tumor and her poor functional status, we offered her off-label treatment with vemurafenib, a BRAF inhibitor approved for use in metastatic melanoma...
August 2014: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Alexandra Arreola, C Lance Cowey, Jonathan L Coloff, Jeffrey C Rathmell, W Kimryn Rathmell
BACKGROUND: Hypoxia Inducible Factors (HIF1α and HIF2α) are commonly stabilized and play key roles related to cell growth and metabolic programming in clear cell renal cell carcinoma. The relationship of these factors to discretely alter cell metabolic activities has largely been described in cancer cells, or in hypoxic conditions, where other confounding factors undoubtedly compete. These transcription factors and their specific roles in promoting cancer metabolic phenotypes from the earliest stages are poorly understood in pre-malignant cells...
2014: PloS One
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