tbuckley/cabot-search huggingface dataset:
Serious Asthma Events with Budesonide plus Formoterol vs. Budesonide Alone
Authors: Stephen P. Peters, Eugene R. Bleecker, Giorgio W. Canonica, Yong B. Park, Ricardo Ramirez, Sally Hollis, Harald Fjallbrant, Carin Jorup, Ubaldo J. Martin
Journal: New England Journal of Medicine (2016)

Concerns remain about the safety of adding long-acting β2-agonists to inhaled glucocorticoids for the treatment of asthma. In a postmarketing safety study mandated by the Food and Drug Administration, we evaluated whether the addition of formoterol to budesonide maintenance therapy increased the risk of serious asthma-related events in patients with asthma.In this multicenter, double-blind, 26-week study, we randomly assigned patients, 12 years of age or older, who had persistent asthma, were receiving daily asthma medication, and had had one to four asthma exacerbations in the previous year to receive budesonide-formoterol or budesonide alone. Patients with a history of life-threatening asthma were excluded. The primary end point was the first serious asthma-related event (a composite of adjudicated death, intubation, and hospitalization), as assessed in a time-to-event analysis. The noninferiority of budesonide-formoterol to budesonide was defined as an upper limit of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The primary efficacy end point was the first asthma exacerbation, as assessed in a time-to-event analysis.A total of 11,693 patients underwent randomization, of whom 5846 were assigned to receive budesonide-formoterol and 5847 to receive budesonide. A serious asthma-related event occurred in 43 patients who were receiving budesonide-formoterol and in 40 patients who were receiving budesonide (hazard ratio, 1.07; 95% confidence interval [CI], 0.70 to 1.65]); budesonide-formoterol was shown to be noninferior to budesonide alone. There were two asthma-related deaths, both in the budesonide-formoterol group; one of these patients had undergone an asthma-related intubation. The risk of an asthma exacerbation was 16.5% lower with budesonide-formoterol than with budesonide (hazard ratio, 0.84; 95% CI, 0.74 to 0.94; P=0.002).Among adolescents and adults with predominantly moderate-to-severe asthma, treatment with budesonide-formoterol was associated with a lower risk of asthma exacerbations than budesonide and a similar risk of serious asthma-related events. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01444430 .).
An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling
Authors: Zoi Karoulia, Yang Wu, Tamer A. Ahmed, Qisheng Xin, Julien Bollard, Clemens Krepler, Xuewei Wu, Chao Zhang, Gideon Bollag, Meenhard Herlyn, James A. Fagin, Amaia Lujambio, Evripidis Gavathiotis, Poulikos I. Poulikakos
Journal: Cancer Cell (2016)
Single-Cell Characterization of Viral Translation-Competent Reservoirs in HIV-Infected Individuals
Authors: Amy E. Baxter, Julia Niessl, Rémi Fromentin, Jonathan Richard, Filippos Porichis, Roxanne Charlebois, Marta Massanella, Nathalie Brassard, Nirmin Alsahafi, Gloria-Gabrielle Delgado, Jean-Pierre Routy, Bruce D. Walker, Andrés Finzi, Nicolas Chomont, Daniel E. Kaufmann
Journal: Cell Host & Microbe (2016)
Durable Responses in Patients Treated with Galiximab (Anti-CD80) in Combination with Rituximab for Relapsed or Refractory Follicular Lymphoma: Long-Term Follow-up of a Phase II Clinical Trial.
Authors: Jonathan W. Friedberg, Anas Younes, David C. Fisher, Leo I. Gordon, Joseph O. Moore, Myron S. Czuczman, Thomas P. Miller, Patrick J. Stiff, Bruce D. Cheson, Andres Forero-Torres, Byron McKinney, John P. Leonard
Journal: Blood (2008)
Mindfulness-Based Stress Reduction vs Cognitive Behavioral Therapy for Chronic Low Back Pain—Reply
Authors: Daniel C. Cherkin, Karen J. Sherman, Judith A. Turner
Journal: JAMA (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 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
Alpha-2-Macroglobulin Is a Major Determinant Of a Lower Thrombin Generation In Infants and Children Compared To Adults
Authors: Romy Kremers, Saartje Bloemen, Raed Al Dieri, Coen H Hemker, Vasiliki Karlaftis, Chantal Attard, Bas de Laat, Paul Monagle, Vera Ignjatovic
Journal: Blood (2013)
Assessing Immune-Related Adverse Events of Efficacious Combination Immunotherapies in Preclinical Models of Cancer
Authors: Jing Liu, Stephen J. Blake, Heidi Harjunpää, Kirsten A. Fairfax, Michelle C.R. Yong, Stacey Allen, Holbrook E. Kohrt, Kazuyoshi Takeda, Mark J. Smyth, Michele W.L. Teng
Journal: Cancer Research (2016)

New combination immunotherapies are displaying both efficacy and immune-related adverse events (irAE) in humans. However, grade 3/4 irAEs occur in a high proportion, which can lead to discontinuation of treatment and can result in fatalities if not promptly treated. Prolonged T regulatory cell (Treg) depletion in tumor-bearing Foxp3-DTR mice using diphtheria toxin (DT) mirrored the spectrum of antitumor responses and severity of irAEs that can occur in ipilimumab/nivolumab-treated patients. In contrast, transient Treg depletion or anti-CTLA-4/PD-1 therapy had equivalent effects in mice, lowering the immune tolerance threshold and allowing irAEs to be more easily induced following treatment with additional immunomodulatory antibodies. Transient Treg depletion of DT in combination with anti-PD-1 or anti-TIM-3 monoclonal antibodies had a high therapeutic window compared with DT plus anti-CD137. In contrast, DT plus anti-CD137-treated mice developed severe irAEs similar to grade 3/4 clinical symptoms. These irAEs appeared because of an infiltration of activated proliferating effector T cells in the tissues producing IFNγ and TNF; however, TNF blockade decreased irAEs severity without impacting on tumor growth. Cancer Res; 76(18); 5288-301. ©2016 AACR.
Permissive Underfeeding or Standard Enteral Feeding in High– and Low–Nutritional-Risk Critically Ill Adults. <i>Post Hoc</i> Analysis of the PermiT Trial
Authors: Yaseen M. Arabi, Abdulaziz S. Aldawood, Hasan M. Al-Dorzi, Hani M. Tamim, Samir H. Haddad, Gwynne Jones, Lauralyn McIntyre, Othman Solaiman, Maram H. Sakkijha, Musharaf Sadat, Shihab Mundekkadan, Anand Kumar, Sean M. Bagshaw, Sangeeta Mehta
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

The optimal nutritional strategy for critically ill adults at high nutritional risk is unclear.To examine the effect of permissive underfeeding with full protein intake compared with standard feeding on 90-day mortality in patients with different baseline nutritional risk.This is a post hoc analysis of the PermiT (Permissive Underfeeding versus Target Enteral Feeding in Adult Critically Ill Patients) trial.Nutritional risk was categorized by the modified Nutrition Risk in Critically Ill score, with high nutritional risk defined as a score of 5-9 and low nutritional risk as a score of 0-4. Additional analyses were performed by categorizing patients by body mass index, prealbumin, transferrin, phosphate, urinary urea nitrogen, and nitrogen balance. Based on the Nutrition Risk in Critically Ill score, 378 of 894 (42.3%) patients were categorized as high nutritional risk and 516 of 894 (57.7%) as low nutritional risk. There was no association between feeding strategy and mortality in the two categories; adjusted odds ratio (aOR) of 0.84 (95% confidence interval [CI], 0.56-1.27) for high nutritional risk and 1.01 (95% CI, 0.64-1.61) for low nutritional risk (interaction P = 0.53). Findings were similar in analyses using other definitions, with the exception of prealbumin. The association of permissive underfeeding versus standard feeding and 90-day mortality differed when patients were categorized by baseline prealbumin level (≤0.10 g/L: aOR, 0.57 [95% CI, 0.31-1.05]; >0.10 and ≤0.15 g/L: aOR, 0.79 [95% CI, 0.42-1.48]; >0.15 g/L: aOR, 1.55 [95% CI, 0.80, 3.01]; interaction P = 0.009).Among patients with high and low nutritional risk, permissive underfeeding with full protein intake was associated with similar outcomes as standard feeding.
Ambulance Diversion and Survival Among Patients With Acute Myocardial Infarction--Reply
Authors: Y.-C. Shen, R. Y. Hsia
Journal: JAMA (2011)

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 Journals 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
Analysis of T-Cell Leukemia/Lymphoma (TCL1) Oncoprotein Interacting Proteins by Immunoprecipitation and Tandem Mass Spectrometry.
Authors: Kojo S.J. Elenitoba-Johnson, Venkatesha Basrur, Adam Kronk, Charles Seiler, Damian Fermin, Alexey Nesvizhskii, Megan S. Lim
Journal: Blood (2007)
The effect of a home-based walking exercise program among men with prostate cancer receiving androgen deprivation therapy: A feasibility trial.
Authors: Y. Lau, P. Czaykowski, J. R. Gingerich, J. Sathya, D. Drachenberg, D. Kriellaars, L. Weinberg, W. Leslie, C. E. Lee
Journal: Journal of Clinical Oncology (2010)

e15152 Background: Androgen deprivation therapy (ADT) is the mainstay therapy for men with advanced prostate cancer. However, there are a number of side effects of ADT that negatively impact the health-related quality of life (HRQL) in these men. We therefore hypothesize that a simple and accessible home-based exercise program can promote the HRQL of men with prostate cancer receiving ADT. The primary goal of the study is to examine the feasibility of such study. Methods: A 12-month prospective, randomized controlled trial was conducted to compare the exercise group with the control group. Men with prostate cancer who would start ADT were recruited and randomly assigned to: (1) Exercise group would receive instructions in setting up an individualized home-based walking exercise program, or (2) control group would have standard medical advice from the attending physician. Each participant was provided with a pedometer for tracking daily activity and he would record time spent in physical activity. A strurctured phone survey was conducted every 2 weeks during the progression phase until they achieved the maximal level of prescribed exercise regimen. The outcome measures used to assess health-related quality of life, physical and cognitive functions at baseline and every 3 months included SF-36, FACT- P, and FACT-Fatigue scale, SPPB, and 6-Minute Walk Test, and Prospective Retrospective Memory Questionnaire. A MANOVA was conducted to determine the differences between the groups. Results: Six patients were recruited in the feasibility study (exercise group= 4 and control group =2). We report three-month follow-up data. Over 3-month period, there were no safety issues reported in both groups. The adherence to the structured walking exercise session was 100 %. The target daily step count adherence was 89%. Though our preliminary data at 3 months have not yet reached significant differences between the two groups except for prospective retrospective memory (p= 0.044), there was a trend favoring the exercise group. Conclusions: This pilot study suggests that home-based walking exercise program is feasible and may potentially positive effects on health-related quality of life. No significant financial relationships to disclose.
India’s private sector needs to take greater role in tuberculosis care
Authors: Sanjeet Bagcchi
Journal: BMJ (2016)

India’s private medical sector needs to get more involved in the management and control of tuberculosis, researchers reporting in two new studies in Lancet Infectious Diseases have said.1 2

The first study, led by Nimalan Arinaminpathy, senior lecturer at the Department of Infectious Disease Epidemiology, Imperial College London, considered the sales of 189 antituberculosis drugs in India during 2013-14 to calculate the number of patients who were treated in the private sector in that period. It estimated that the number of cases of tuberculosis treated in the private sector in 2014 was 2.2 million, more than double the currently estimated number …
A Phase 1 Study of the PARP Inhibitor Veliparib in Combination with Temozolomide in Acute Myeloid Leukemia
Authors: Ivana Gojo, Jan H. Beumer, Keith W. Pratz, Michael A. McDevitt, Maria R. Baer, Amanda L. Blackford, B. Douglas Smith, Steven D. Gore, Hetty E. Carraway, Margaret M. Showel, Mark J. Levis, Amy E. Dezern, Douglas E. Gladstone, Jiuping Jay Ji, Lihua Wang, Robert J. Kinders, Marie Pouquet, Ismail Ali-Walbi, Michelle A. Rudek, Weijie Poh, James G. Herman, Larry M. Karnitz, Scott H. Kaufmann, Alice Chen, Judith E. Karp
Journal: Clinical Cancer Research (2016)

In preclinical studies, the PARP inhibitor veliparib enhanced the antileukemic action of temozolomide through potentiation of DNA damage. Accordingly, we conducted a phase 1 study of temozolomide with escalating doses of veliparib in patients with relapsed, refractory acute myeloid leukemia (AML) or AML arising from aggressive myeloid malignancies.
Increased PI3K/Akt activity and deregulated humoral immune response in human PTEN deficiency
Authors: Gertjan J. Driessen, Hanna IJspeert, Marjolein Wentink, Helger G. Yntema, P. Martin van Hagen, Arthur van Strien, Giorgia Bucciol, Ozgur Cogulu, Margreet Trip, Willy Nillesen, Els A. Peeters, Ingrid Pico-Knijnenburg, Barbara H. Barendregt, Marta Rizzi, Jacques J. van Dongen, Necil Kutukculer, Mirjam van der Burg
Journal: Journal of Allergy and Clinical Immunology (2016)
Optical Coherence Tomography Angiography of DME and Its Association with Anti-VEGF Treatment Response
Authors: Junyeop Lee, Byung Gil Moon, Ah Ran Cho, Young Hee Yoon
Journal: Ophthalmology (2016)

To investigate the structural integrity of the superficial capillary plexuses (SCPs) and deep capillary plexuses (DCPs) using optical coherence tomography (OCT) angiography (OCTA) in patients with diabetic macular edema (DME) and its association with the response to anti-vascular endothelial growth factor (VEGF) treatment.Retrospective, case-control study.We included 51 DME eyes with a poor response to anti-VEGF agents and 32 age-matched DME eyes with a good response to anti-VEGF treatment, along with 20 fellow eyes without DME from the cases and controls.The medical records, including OCTA and spectral-domain OCT (SD OCT), were reviewed and compared between the groups. En face OCTA images of the SCP and DCP were obtained for each eye. An anti-VEGF responder was defined by a reduction of more than 50 μm in central retinal thickness after 3 consecutive anti-VEGF treatments. A poor responder was defined by a reduction of less than 50 μm or an increase in central retinal thickness after 3 monthly injections.We measured the vascular density and foveal avascular zone (FAZ) area and counted the number of microaneurysms in each layer. The SD OCT images were compared with OCTA findings.Compared with non-DME eyes, DME eyes had a lower vascular density (P < 0.001) and larger FAZ area (P < 0.001) in the DCP and more microaneurysms (P < 0.001) in both layers. Although there was no significant difference in the SCP between anti-VEGF responders and poor responders, poor responders tended to show greater damage and more microaneurysms in the DCP (P < 0.001) and a larger FAZ area (P < 0.001). The topographic location of the disrupted synaptic portion of the outer plexiform layer (OPL) in SD OCT exactly corresponded to the nonflow area of the DCP in OCTA.Compared with DME eyes that responded to anti-VEGF treatment, poor responders show significant damage to the integrity of the DCP, but not the SCP. The degree of OPL disruption in SD OCT corresponds well with the extent of DCP loss in DME eyes. The extent of DCP loss and the corresponding OPL disruption could be useful predictors of responsiveness to anti-VEGF treatment.
Onartuzumab plus erlotinib versus erlotinib in previously treated stage IIIb or IV NSCLC: Results from the pivotal phase III randomized, multicenter, placebo-controlled METLung (OAM4971g) global trial.
Authors: David R. Spigel, Martin J. Edelman, Kenneth O'Byrne, Luis Paz-Ares, David S. Shames, Wei Yu, Virginia E. Paton, Tony Mok
Journal: Journal of Clinical Oncology (2014)

8000 Background: A placebo-controlled, phase II trial of erlotinib + onartuzumab, a humanized monovalent antibody to the MET receptor, demonstrated a benefit in progression-free survival (PFS) when compared with erlotinib in patients with MET-positive NSCLC (JCO 2013;31;4105). The aim of the METLung trial was to confirm the efficacy and safety of onartuzumab + erlotinib in MET-positive NSCLC. Methods: This prospective, randomized, double-blind, placebo-controlled trial enrolled patients with previously treated MET-positive stage IIIb/IV NSCLC. MET diagnostic status was determined by an immunohistochemistry (IHC) assay using the CONFIRM anti-total MET SP44 monoclonal antibody (Ventana). Eligibility criteria included: ECOG PS 0–1, 1–2 prior lines of chemotherapy, and normal organ function. Stratification factors: EGFR mutation status (activating mutation vs negative; cobas® EGFR assay), MET IHC (2+ vs 3+), number of prior treatments (1 vs 2), and histology (squamous vs non-squamous). Patients were randomized (1:1) to receive erlotinib 150mg PO daily + placebo or onartuzumab 15mg/kg IV every 21 days. Tumor assessments occurred every 6 weeks. The primary endpoint was overall survival (OS). The sample size (n=490) was based on the assumption that adding onartuzumab to erlotinib would improve OS by 41% with 90% power (one-sided alpha 0.025). An interim analysis was planned when 67% (244 events) of the final events were reached. Results: 499 patients were enrolled between Jan 2012 and Aug 2013. An independent data review committee recommended to stop the trial for futility, as the addition of onartuzumab to erlotinib did not improve OS (HR 1.27, p=0.068; median OS 6.8 mos vs 9.1 mos), PFS (HR 0.99, p=0.92; median PFS 2.7 mos vs 2.6 mos), or overall response rate (8.4% vs 9.6%; p=0.63). The most frequent adverse events that were higher in the combination arm were peripheral edema, hypoalbuminemia, back pain, dyspnea, nausea, acneiform dermatitis, and rash. Conclusions: The phase III study did not confirm the efficacy results observed in the phase II study. Exploratory analyses based on molecular subgroups are pending. Clinical trial information: NCT01456325.
Re: Christopher J.D. Wallis, Refik Saskin, Richard Choo, et al. Surgery Versus Radiotherapy for Clinically-localized Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol 2016;70:21–30
Authors: Alison C. Tree, Nicholas J. van As, David P. Dearnaley
Journal: European Urology (2016)
Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia
Authors: Marina Konopleva, Daniel A. Pollyea, Jalaja Potluri, Brenda Chyla, Leah Hogdal, Todd Busman, Evelyn McKeegan, Ahmed Hamed Salem, Ming Zhu, Justin L. Ricker, William Blum, Courtney D. DiNardo, Tapan Kadia, Martin Dunbar, Rachel Kirby, Nancy Falotico, Joel Leverson, Rod Humerickhouse, Mack Mabry, Richard Stone, Hagop Kantarjian, Anthony Letai
Journal: Cancer Discovery (2016)

We present a phase II, single-arm study evaluating 800 mg daily venetoclax, a highly selective, oral small-molecule B-cell leukemia/lymphoma-2 (BCL2) inhibitor in patients with high-risk relapsed/refractory acute myelogenous leukemia (AML) or unfit for intensive chemotherapy. Responses were evaluated following revised International Working Group (IWG) criteria. The overall response rate was 19%; an additional 19% of patients demonstrated antileukemic activity not meeting IWG criteria (partial bone marrow response and incomplete hematologic recovery). Twelve (38%) patients had isocitrate dehydrogenase 1/2 mutations, of whom 4 (33%) achieved complete response or complete response with incomplete blood count recovery. Six (19%) patients had BCL2-sensitive protein index at screening, which correlated with time on study. BH3 profiling was consistent with on-target BCL2 inhibition and identified potential resistance mechanisms. Common adverse events included nausea, diarrhea and vomiting (all grades), and febrile neutropenia and hypokalemia (grade 3/4). Venetoclax demonstrated activity and acceptable tolerability in patients with AML and adverse features.Venetoclax monotherapy demonstrated clinical activity in patients with AML (relapsed/refractory or unfit for intensive chemotherapy) with a tolerable safety profile in this phase II study. Predictive markers of response consistent with BCL2 dependence were identified. Clinical and preclinical findings provide a compelling rationale to evaluate venetoclax combined with other agents in AML. Cancer Discov; 6(10); 1106-17. ©2016 AACRSee related commentary by Pullarkat and Newman, p. 1082This article is highlighted in the In This Issue feature, p. 1069.
Early-Life Origins of Chronic Obstructive Pulmonary Disease
Authors: Fernando D. Martinez
Journal: New England Journal of Medicine (2016)

The conventional thinking about COPD is that exposures in adult life, such as smoking, lead to a low FEV1:FVC ratio, the physiological hallmark of COPD. In this review, the effect of early-life exposures on the lung that could lead to expiratory airflow limitation is reviewed.