tbuckley/cabot-search huggingface dataset:
Fish Oils and Bleeding—Where Is the Evidence?—Reply
Authors: Dima M. Qato, G. Caleb Alexander
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
A Comparison of Conditioning Regimens with or without Alemtuzumab for Sibling RIC Transplants for AML: Study from the British Society for Blood and Marrow Transplantation.
Authors: Ram K. Malladi, Andrew J. Peniket, Timothy James Littlewood, Keiren E. Towlson, Rachel Pearce, John Yin, Jamie D. Cavanagh, Charles Craddock, Kim H. Orchard, David I. Marks
Journal: Blood (2006)
Pemetrexed plus gemcitabine versus gemcitabine plus carboplatin in patients with advanced nonoperable NSCLC: A randomized phase II study.
Authors: G. N. Hillerdal, H. Koyi, E. Brandén, K. Kolbeck
Journal: Journal of Clinical Oncology (2010)

e18039 Background: The standard first-line treatment of inoperable Non-Small Cell Lung Cancer (NSCLC) is a combination of two drugs, one of which should be a platinum drug. We investigated a combination of two modern drugs without platinum in a single institute randomized study. Methods: Consecutive patients with NSCLC, stage III B inoperable or IV, PS 0-2, September 2006-October 2009, were randomized to pemetrexed, 500 mg/m2 + gemcitabine, 1,500 mg/m2 every second week (PG arm), or gemcitabine, 1,250 mg/m2 day 1 and 8 and carboplatin 5 AUC day 1 every 3 weeks (GC arm). Unless progression of disease, toxicity, or withdrawal of consent, 6 courses were given in the PG arm and 4 courses in the AG arm. Results: Forty-seven patients were randomized to the PG and 50 to the GC arm. Three patients were excluded, leaving 46 in the PG and 48 in the GC arm. In the PG arm, 22% stopped treatment due to side effects, and 4% in the GC arm. The only lethal side effect was seen in the GC arm. In the PG arm, 20% stopped treatment because of progressive disease vs. 24% in the GC. In the PG, 21 had a PR and 1 a CR (48% OR), while 15 had PR and no one CR in the GC group (31%). TTP was similar in both groups (3 months), but 11 PG patients (24%) had a TTP > 6 months while in the GC group only 2 (4%) had so. Conclusions: Despite the higher dose intensity in the PG arm, the majority tolerated the treatment. There was a tendency to more responses and a longer TTP in the PG arm. Further analyses are therefore warranted. It seems, however, that platinum-free drug regimens can give as good results as those with platinum. No significant financial relationships to disclose.
Are experimental economists behaviorists and is behaviorism for the birds?
Authors: Robert Kurzban
Journal: Behavioral and Brain Sciences (2001)

Methods in experimental economics are reminiscent of the methods employed by behaviorists in the first half of the twentieth century. Empirical and conceptual progress led the field of psychology away from the principles of behaviorism, and experimental economists should consider whether the criticisms leveled against behaviorists might apply equally to them.
Diffuse Progressive Proliferation of Dark Papules in an Otherwise Healthy African American Woman
Authors: W. C. Cole Claiborne, Ashley E. Morgan, Andrea Tesvich Murina
Journal: JAMA Dermatology (2016)

An African American woman in her 30s with no medical history presented with a 4-year history of diffuse progressive proliferation of dark papules with first onset several weeks after a sunburn. What is your diagnosis?
Interferon Alfa Versus Chemotherapy for Chronic Myeloid Leukemia: A Meta-analysis of Seven Randomized Trials
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Several randomized clinical trials in chronic myeloid leukemia (CML) have reported better patient survival with interferon alfa (IFN α) than with standard chemotherapeutic agents, such as busulfan or hydroxyurea. However, the size and persistence of this survival benefit is uncertain. Our aim was to assess these reliably, both overall and in particular patient subgroups. Methods: We collaborated in a worldwide overview of all clinical trials in which patients with CML were randomly assigned to receive either IFN α as the main drug or standard chemotherapy. Trials were identified by electronic and hand searching of the medical literature and databases and by personal contact. Individual patient data were available for each of 1554 patients who had been randomly assigned to treatment in seven trials (German, Italian, British, French, Japanese, and "Benelux"). Intentionto- treat stratified logrank survival analyses were performed, reporting two-sided P values. Results: Almost all of the patients in these trials had disease with the Philadelphia chromosome abnormality. Among those who did, the regimens that involved IFN α produced a statistically significantly better survival than those involving either hydroxyurea ( P = .001) or busulfan ( P = .00007) alone. The 5-year survival rates were 57% with IFN α and 42% with chemotherapy, with an absolute difference of 15% (standard deviation = 3%; P <.00001). There were no trials or subgroups of patients in which the treatment difference was statistically significantly different from the average. Conclusion: For patients with Philadelphia chromosome-positive chronic myeloid leukemia, the inclusion of IFN α in the therapeutic regimen produced substantially better 5-year survival than standard chemotherapy alone.
GP recruits offered £20 000 to train in Scotland
Authors: Bryan Christie
Journal: BMJ (2016)

Incentive payments of £20 000 are being offered to junior doctors who choose to train as general practitioners in areas of Scotland where posts have been hard to fill.

The payments are part of the Scottish government’s response to what has been described as a crisis in GP recruitment which resulted last year in vacancies in a fifth of all practices.1

Applications are being sought for 100 newly …
Oral Melphalan, Prednisone, and Lenalidomide for Newly Diagnosed Multiple Myeloma Patients: Kinetics of Neutropenia/Thrombocytopenia and Time to Event Results
Authors: Antonio Palumbo, Patrizia Falco, Francesca Gay, Paolo Corradini, Claudia Crippa, Francesco Di Raimondo, Antonietta Falcone, Nicola Giuliani, Pellegrino Musto, Fortunato Morabito, Letizia Canepa, Alessandro Gozzetti, Simona Caltagirone, Jerome B. Zeldis, Robert D. Knight, Mario Boccadoro, Maria Teresa Petrucci
Journal: Blood (2008)
Risk of Chlamydial PID and Oral Contraceptives
Authors: N. Job-Spira
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Wølner-Hanssen et al<sup>1</sup>report a decreased risk of symptomatic chlamydial pelvic inflammatory disease associated with oral contraceptive use. Pelvic inflammatory disease is the principal cause of ectopic pregnancy (EP), yet our recent findings do not indicate a decreased risk of EP with use of oral contraceptives. <h3>Study. —</h3> We conducted a case-control study between January 1988 and March 1989 in seven departments of obstetrics and gynecology in the Paris area. A group of 279 patients with EP, confirmed by laparoscopy or laparotomy, were individually matched with two control women: the first woman admitted to give birth and the first woman admitted with a miscarriage to the same department. The case women and control women were interviewed with respect to prior gynecologic disease and surgical procedures, pregnancy history, contraceptive use at the time of the current conception, sexual activity, smoking habits, and constitutional and socioeconomic factors. The
Targeted Cancer Therapy: pH-Switch Nanoprecipitation of Polymeric Nanoparticles for Multimodal Cancer Targeting and Intracellular Triggered Delivery of Doxorubicin (Adv. Healthcare Mater. 15/2016)
Authors: Bárbara Herranz-Blanco, Mohammad-Ali Shahbazi, Alexandra R. Correia, Vimalkumar Balasubramanian, Tomáš Kohout, Jouni Hirvonen, Hélder A. Santos
Journal: Advanced Healthcare Materials (2016)

Targeted theranostic nanoparticles with dual pH and magnetic responsive properties for intracellular delivery are described by B. Herranz-Blanco, H. A. Santos, and co-workers on page 1904. Using a pH-switch nanoprecipitation method in organic-free solvents, a polymeric-drug conjugate solid nanoparticle containing encapsulated superparamagnetic iron oxide nanoparticles and decorated with a tumor homing peptide, iRGD, are targeted to endothelial and metastatic cancer cells.
Utility of 18 F-FDG PET for Predicting Histopathologic Response in Esophageal Carcinoma following Chemoradiation
Authors: Andrea L.H. Arnett, Kenneth W. Merrell, Erica Martin Macintosh, Sarah E. James, Mark A. Nathan, K. Robert Shen, Karthik Ravi, Michelle A. Neben Wittich, Michael G. Haddock, Christopher L. Hallemeier
Journal: Journal of Thoracic Oncology (2016)
Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness
Authors: Giulio Fracasso, Elisabetta Falvo, Gianni Colotti, Francesco Fazi, Tiziano Ingegnere, Adriana Amalfitano, Giovanni Battista Doglietto, Sergio Alfieri, Alberto Boffi, Veronica Morea, Giamaica Conti, Elisa Tremante, Patrizio Giacomini, Alessandro Arcovito, Pierpaolo Ceci
Journal: Journal of Controlled Release (2016)
Critical Care Medicine
Authors: John G. Weg
Journal: JAMA (1989)

The prospective, randomized, double-blind, placebo-controlled clinical trial remains quintessential in resolving often complex, controversial clinical problems. Its importance is epitomized in the resolution of the decades-old debate over the role of corticosteroids in septic shock and in the adult respiratory distress syndrome (ARDS).<i>Corticosteroids do not help, and they may hurt</i>. The Veterans Administration Systemic Sepsis Cooperative Study Group<sup>1</sup>randomized patients with clinical signs of sepsis and a normal sensorium to receive methylprednisolone sodium succinate (30 mg/kg by intravenous bolus and then 5 mg/kg per hour for 9 hours) or placebo. One hundred twelve patients received the study drug and 111 served as controls. The average time between the diagnosis of sepsis and infusion was 2.8 hours. At 14 days, there was no difference in the main end point of mortality rates, which were 21% for the methylprednisolone group and 22% for the placebo group; nor was there any
2017 Clinical trials update in new treatments of β‐thalassemia
Authors: Alexandros Makis, Eleftheria Hatzimichael, Ioannis Papassotiriou, Ersi Voskaridou
Journal: American Journal of Hematology (2016)

The underlying basis of β-thalassemia pathology is the diminished β-globin synthesis leading to α-globin accumulation and premature apoptotic destruction of erythroblasts, causing oxidative stress-induced ineffective erythropoiesis, bone marrow hyperplasia, splenomegaly, and increased intestinal iron absorption with progressive iron overload. Better understanding of the molecular mechanisms underlying this disease led to the recognition of new targets with potential therapeutic utility. Agents such as JAK2 inhibitors and TGF-β ligand traps that reduce the ineffective erythropoiesis process are already being tested in clinical trials with promising results. Other agents that aim to reduce oxidative stress (activators of Foxo3, HRI-eIF2aP, Prx2, Hsp70, and PK anti-oxidant systems and inhibitors of HO-1) and to decrease iron overload (hepcidin agonists, erythroferrone inhibitors and exogenous transferrin) are also under experimental investigation. Significant progress has also been made in the area of allogeneic hematopoietic stem cell transplantation with several ongoing clinical trials examining new condition regimens as well as different donor selection and stem cell source options. Gene therapy has reached a critical point and phase 1 clinical trials have recently been launched to examine the effectiveness and especially long term safety. Epigenetic manipulation and genomic editing of the γ- or β-globin gene are novel and promising experimental gene therapy approaches for β-thalassemia giving hope for cure for this chronic disease. This review outlines the key points of the molecular mechanisms underlying β-thalassemia in relation to the development of new therapies and an update is given both at the pre-clinical and clinical level. Am. J. Hematol. 91:1135-1145, 2016. © 2016 Wiley Periodicals, Inc.
Toward Precision Medicine: <i>TBC1D4</i> Disruption Is Common Among the Inuit and Leads to Underdiagnosis of Type 2 Diabetes
Authors: Despoina Manousaki, Jack W. Kent, Karin Haack, Sirui Zhou, Pingxing Xie, Celia M. Greenwood, Paul Brassard, Deborah E. Newman, Shelley Cole, Jason G. Umans, Guy Rouleau, Anthony G. Comuzzie, J. Brent Richards
Journal: Diabetes Care (2016)

A common nonsense mutation in TBC1D4 was recently found to substantially increase the odds of type 2 diabetes in Greenlandic Inuit, leading to exclusively increased postprandial glucose. We investigated the frequency and effect of the TBC1D4 mutation on glucose metabolism and type 2 diabetes diagnosis among Canadian and Alaskan Inuit.Exome sequencing of the TBC1D4 variant was performed in 114 Inuit from Nunavik, Canada, and Sanger sequencing was undertaken in 1,027 Alaskan Inuit from the Genetics of Coronary Artery Disease in Alaskan Natives (GOCADAN) Study. Association testing evaluated the effect of the TBC1D4 variant on diabetes-related metabolic traits and diagnosis.The TBC1D4 mutation was present in 27% of Canadian and Alaskan Inuit. It was strongly associated with higher glucose (effect size +3.3 mmol/L; P = 2.5 x 10-6) and insulin (effect size +175 pmol/L; P = 0.04) 2 h after an oral glucose load in homozygote carriers. TBC1D4 carriers with prediabetes and type 2 diabetes had an increased risk of remaining undiagnosed unless postprandial glucose values were tested (odds ratio 5.4 [95% CI 2.5-12]) compared with noncarriers. Of carriers with prediabetes or type 2 diabetes, 32% would remain undiagnosed without an oral glucose tolerance test (OGTT).Disruption of TBC1D4 is common among North American Inuit, resulting in exclusively elevated postprandial glucose. This leads to underdiagnosis of type 2 diabetes, unless an OGTT is performed. Accounting for genetic factors in the care of Inuit with diabetes provides an opportunity to implement precision medicine in this population.
Durable response of the triple combination of temozolomide, sorafenib, and bevacizumab to treat refractory stage IV acral melanoma.
Authors: L. Si, M. Han, Z. H. Chi, C. L. Cui, X. N. Sheng, S. M. Li, Y. Kong, J. Guo
Journal: Journal of Clinical Oncology (2010)

8564 Background: Metastatic acral melanoma is a rapid progressing and refractory disease which accounts for 50% in China. VEGF, MAPK and NF-KB, which are targets of bevacizumab, sorafenib and temozolomide (TMZ) respectively, are vertical joint which inhibits melanoma cells from membrane, cytoplasm to nuclei. We conducted a phase II trial of the triple combination to test synergistic effects on metastatic acral melanoma. Methods: Patients (Pts) with stage IV (M1c) unresectable acral melanoma, who have failed at least one systemic regimen, are eligible. The pts were treated with TMZ 200 mg/m2/d (days 1- 5), bevacizumab 5 mg/Kg (days 1, 14) and sorafenib 400 mg/bid (days 1-28), repeatedly every 28 days. KIT, VEGFR and PDGFR protein of tumor tissue were detected and genetic aberrations including KIT and BRAF were analyzed by Immunohistrochemistry (IHC) assay and DNA sequencing respectively. The endpoints were progression-free survival (PFS), overall survival (OS), response and toxicity. Correlation was decided between gene mutations, IHC results and clinical response. Results: 50 patients were planned to recruit. 35 pts were currently enrolled and evaluated. One patient has achieved complete response (CR) lasting 16+months. Eight pts have achieved partial response (PR) (duration range: 4.4∼7.2+ months). 15 pts received SD (> 3 m) with duration from 3.2 to 12+months. The response rate was 25.7% (9/35). PFS has not reached (at least 3.8 months). It's too early to assess overall survival. 30 pts had IHC and aberration results. The positive rates of KIT protein were 35% (PR+SD) pts and 42% in PD pts, of VEGFR were 26% s and 57%; of PDGFR were 84% and 57% respectively (p > 0.05). Five patients were found harboring BRAF V600E mutations (1CR, 4PD) and one of them had KIT amplification simultaneously (response: PD). The common toxicity was moderate including hand-foot syndrome (G3/4:11.4%), myelosuppression (G3/4:11.4%), diarrhea (G3/4:2.8%), fatigue and hoarse. Conclusions: The triple combination regimen preliminary achieved durable clinical response. The regimen is safe and well tolerated. It seemed no correlation between positive IHC results, gene mutations and responses. No significant financial relationships to disclose.
A randomized, phase 3, open-label study of nivolumab versus temozolomide (TMZ) in combination with radiotherapy (RT) in adult patients (pts) with newly diagnosed, O-6-methylguanine DNA methyltransferase (MGMT)-unmethylated glioblastoma (GBM): CheckMate-498.
Authors: John H. Sampson, Antonio Marcilio Padula Omuro, Matthias Preusser, Michael Lim, Nicholas A. Butowski, Timothy Francis Cloughesy, Lewis C. Strauss, Robert Raymond Latek, Prashni Paliwal, Michael Weller, David A. Reardon
Journal: Journal of Clinical Oncology (2016)

TPS2079 Background: GBM, the most common primary brain tumor in adults, has an aggressive clinical course and a median survival of 15–18 months in clinical trial populations. Approximately 40% of pts with GBM have tumors with an MGMT-methylated promoter, which is associated with sensitivity to TMZ. New treatment options for pts with GBM are desirable, particularly for those with MGMT-unmethylated GBM, as TMZ efficacy is historically marginal in this population. Nivolumab, a fully human IgG4 monoclonal antibody to the programmed death-1 receptor, has shown clinical activity and increased survival in pts with metastatic melanoma, non–small-cell lung cancer, and renal cell carcinoma. CheckMate-498 (NCT02617589) is a phase 3 study designed to compare overall survival (OS) of nivolumab or TMZ, each in combination with RT, in pts with newly diagnosed MGMT-unmethylated GBM. In a companion phase 2 trial (CheckMate-548; NCT02667587), eligible pts with MGMT-methylated tumors (N = 320) will be randomized to RT + TMZ + nivolumab vs RT + TMZ + placebo, with OS as the primary objective. Methods: Eligibility criteria include newly diagnosed, histologically confirmed, MGMT-unmethylated (centrally confirmed) GBM in pts aged ≥ 18 years with Karnofsky performance status ≥ 70. Pts with prior treatment for GBM and recurrent or secondary GBM are ineligible. Approximately 550 pts will be randomized to receive nivolumab + RT followed by nivolumab, or TMZ + RT followed by TMZ. Treatment will continue until progression or unacceptable toxicity. The primary objective is to compare OS with nivolumab + RT vs TMZ + RT; secondary objectives include progression-free survival and 2-year survival rate. Exploratory objectives include safety, biomarker analyses, and neurocognitive outcomes. Patients will be followed for safety and tolerability, tumor progression, and survival. At least 397 events, with an interim analysis after ≥ 298 events, will provide 90% power to detect a hazard ratio of < 0.72. Clinical trial information: NCT02617589.
The MetLUNG study: A randomized, double-blind, phase III study of onartuzumab (MetMAb) plus erlotinib versus placebo plus erlotinib in patients with advanced, MET-positive non-small cell lung cancer (NSCLC).
Authors: David R. Spigel, Martin J. Edelman, Tony Mok, Kenneth John O'Byrne, Luis Paz-Ares, Wei Yu, Karen Rittweger, Holger C. Thurm
Journal: Journal of Clinical Oncology (2012)

TPS7616 Background: Increased Met signaling is associated with poor prognosis in NSCLC and can result in acquired resistance to epidermal growth factor receptor (EGFR)-targeted drugs in EGFR-mutant lung tumors. Onartuzumab (MetMAb) is a humanized monovalent monoclonal antibody that binds to Met with high specificity, preventing HGF ligand binding and blocking downstream signaling. Onartuzumab has shown anticancer activity in preclinical studies (Merchant et al. AACR 2008:Abstr. 1336) and in a phase I study of patients with advanced solid tumors (Moss et al. Ann Oncol 2010;21(Suppl. 8):Abstr. 504P). In a phase II study, patients with Met-positive tumors (≥50% of tumor cells stain 2+ or 3+ intensity by IHC) (Met Dx+) who received onartuzumab + erlotinib had nearly twofold reduction in the risk of disease progression and threefold reduction in the risk of death compared with erlotinib alone (Spigel et al. J Clin Oncol 2011;29(Suppl.):Abstr. 7505). An increased incidence of peripheral edema was observed in patients treated with onartuzumab. Methods: This is a randomized, phase III, multicenter, double-blind, placebo-controlled study. Adults with Met Dx+ tumors who failed at least 1 but no more than 2 prior lines of platinum-based chemotherapy for advanced NSCLC are eligible. Around 480 patients will receive (1:1) erlotinib (150 mg PO daily) + placebo or onartuzumab (15 mg/kg IV Q3W) until disease progression, unacceptable toxicity, patient/physician decision to discontinue, or death. Patients are stratified for Met expression (2+ vs 3+), prior lines of therapy (1 vs 2), histology (squamous vs nonsquamous) and EGFR-activating mutation status (yes vs no). The primary endpoint is OS. Secondary endpoints include PFS, response rates, safety, patient-reported outcomes, and PK. An IDMC will monitor safety every 6 months after the 1st patient is enrolled and evaluate 1 interim analysis when ~67% of the total OS events have occurred. This study is open for accrual; further details can be found on ClinicalTrials.gov (NCT01456325).