tbuckley/cabot-search huggingface dataset:
Effect of Roflumilast and Inhaled Corticosteroid/Long-Acting β<sub>2</sub>-Agonist on Chronic Obstructive Pulmonary Disease Exacerbations (RE<sup>2</sup>SPOND). A Randomized Clinical Trial
Authors: Fernando J. Martinez, Klaus F. Rabe, Sanjay Sethi, Emilio Pizzichini, Andrew McIvor, Antonio Anzueto, Vijay K. T. Alagappan, Shahid Siddiqui, Ludmyla Rekeda, Christopher J. Miller, Sofia Zetterstrand, Colin Reisner, Stephen I. Rennard
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Moderate and severe exacerbations are incompletely prevented by maximal inhalation therapy in patients with severe chronic obstructive pulmonary disease.Objectives: To determine whether roflumilast reduces moderate and/or severe chronic obstructive pulmonary disease exacerbations in patients at risk for exacerbations despite treatment with inhaled corticosteroid/long-acting β2-agonist with or without a long-acting muscarinic antagonist (LAMA).Methods: In this 52-week, phase 4, double-blind, placebo-controlled RE2SPOND (Roflumilast Effect on Exacerbations in Patients on Dual [LABA/ICS] Therapy) trial (NCT01443845), participants aged 40 years or older with severe/very severe chronic obstructive pulmonary disease, chronic bronchitis, two or more exacerbations and/or hospitalizations in the previous year, and receiving inhaled corticosteroid/long-acting β2-agonist with or without LAMA daily for 3 or more months were equally randomized to once-daily roflumilast, 500 μg (n = 1,178), or placebo (n = 1,176). Stratification was based on LAMA use.Measurements and Main Results: Although rate of moderate or severe exacerbations per patient per year (primary endpoint) was reduced by 8.5% with roflumilast versus placebo, the between-group difference was not statistically significant (rate ratio, 0.92; 95% confidence interval, 0.81–1.04; P = 0.163). However, roflumilast improved lung function, and in a post hoc analysis roflumilast significantly reduced the rate of moderate or severe exacerbations in participants with a history of more than three exacerbations and/or one or more hospitalizations in the prior year. Adverse event–related discontinuations occurred in 11.7% roflumilast-treated and 5.4% placebo-treated participants. Deaths occurred in 2.5% roflumilast and 2.1% placebo participants.Conclusions: Roflumilast failed to statistically significantly reduce moderate and/or severe exacerbations in the overall population. Roflumilast improved lung function and reduced exacerbations in participants with frequent exacerbations and/or hospitalization history. The safety profile of roflumilast was consistent with that of previous studies.Clinical trial registered with www.clinicaltrials.gov (NCT01443845).
Further Misanalysis of Urinalysis
Authors: Dimitri Drekonja
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
Fractional-Dose Inactivated Poliovirus Vaccine Immunization Campaign — Telangana State, India, June 2016
Authors: Sunil Bahl, Harish Verma, Pankaj Bhatnagar, Pradeep Haldar, Asish Satapathy, K. N. Arun Kumar, Jennifer Horton, Concepcion F. Estivariz, Abhijeet Anand, Roland Sutter
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Wild poliovirus type 2 was declared eradicated in September 2015 (1). In April 2016, India, switched from use of trivalent oral poliovirus vaccine (tOPV; containing types 1, 2, and 3 polio vaccine viruses), to bivalent OPV (bOPV; containing types 1 and 3), as part of a globally synchronized initiative to withdraw Sabin poliovirus type 2 vaccine. Concurrently, inactivated poliovirus vaccine (IPV) was introduced into India's routine immunization program to maintain an immunity base that would mitigate the number of paralytic cases in the event of epidemic transmission of poliovirus type 2 (2,3). After cessation of use of type 2 Sabin vaccine, any reported isolation of vaccine-derived poliovirus type 2 (VDPV2) would be treated as a public health emergency and might need outbreak response with monovalent type 2 oral vaccine, IPV, or both (4). In response to identification of a VDPV2 isolate from a sewage sample collected in the southern state of Telangana in May 2016, India conducted a mass vaccination campaign in June 2016 using an intradermal fractional dose (0.1 ml) of IPV (fIPV). Because of a global IPV supply shortage, fIPV, which uses one fifth of regular intramuscular (IM) dose administered intradermally, has been recommended as a response strategy for VDPV2 (5). Clinical trials have demonstrated that fIPV is highly immunogenic (6,7). During the 6-day campaign, 311,064 children aged 6 weeks-3 years were vaccinated, achieving an estimated coverage of 94%. With appropriate preparation, an emergency fIPV response can be promptly and successfully implemented. Lessons learned from this campaign can be applied to successful implementation of future outbreak responses using fIPV.
Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment
Authors: Peter J. Tebben, Ravinder J. Singh, Rajiv Kumar
Journal: Endocrine Reviews (2016)

Abstract Hypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.
Lenalidomide (Revlimid®) +/− Corticosteroids in Elderly Patients with Relapsed/Refractory Multiple Myeloma.
Authors: Donna E. Reece, Esther Masih-Khan, Christine Chen, Lisa Wang, Saima Dean, Suzanne Trudel, Joseph R. Mikhael, Vishal Kukreti, Robert Knight, Jerome Zeldis
Journal: Blood (2006)
Comparison of bortezomib- and lenalidomide-based therapies for the treatment of primary (AL) amyloidosis.
Authors: D. J. Landsburg, E. A. Stadtmauer, S. J. Schuster, P. Mangan, B. Shelly, D. T. Vogl
Journal: Journal of Clinical Oncology (2010)

8026 Background: Current treatment strategies for primary (AL) amyloidosis incorporate the novel anti-myeloma agents bortezomib and lenalidomide. However, a comparative analysis of these therapies has not been reported to date. Here, we describe outcomes in patients with primary amyloidosis treated at our institution with either bortezomib- or lenalidomide-based regimens. Methods: Data for 23 patients with primary amyloidosis who received either bortezomib (n=13) or lenalidomide (n=10) as their first novel agent were included in this retrospective analysis. Bortezomib was dosed at 1.0-1.6 mg/m2 on days 1,4,8,11 of a 21-day cycle or days 1,8,15,22 of a 35-day cycle, with concurrent dexamethasone (100%), cyclophosphamide (15%) and melphalan (8%). Lenalidomide was dosed at 10-25 mg daily on days 1-21 of a 28-day cycle with concurrent dexamethasone (70%) and melphalan (20%). Results: Patients in the bortezomib and lenalidomide groups had similar baseline characteristics, including median age at diagnosis (58 vs. 57.5 years), frequency of cardiac (54% vs. 60%) and multi-organ (69% vs. 70%) involvement and median number of lines of prior therapy (1 for both). Patients treated with bortezomib were more likely to achieve hematologic response (overall response 54% vs. 40%, complete response 15% vs. 10%) and organ response (38% vs. 20%) than those treated with lenalidomide. Time to hematologic and organ response was similar among both groups. Patients treated with bortezomib were more likely to experience toxicity than those treated with lenalidomide (77% vs. 40%), resulting in more frequent dose-reduction or discontinuation (54% vs. 40%). The primary toxicities reported were neuropathy (54%) in patients receiving bortezomib and neuropathy and cytopenias (20% each) in patients receiving lenalidomide. Estimated one-year survival rates were similar between patients in the bortezomib and lenalidomide groups (74% vs. 80%). Statistical significance was not achieved for these results. Conclusions: In patients with primary amyloidosis, treatment with bortezomib-based therapies may be more likely to result in hematologic and organ response as well as toxicity in comparison to lenalidomide-based therapies. No significant financial relationships to disclose.
Positron Emission Tomographic Scans in Depressive Disorders-Reply
Authors: Jeffrey M. Schwartz
Journal: JAMA (1988)

<h3>In Reply.</h3> —An intriguing issue is raised by Dr Dilsaver and Mr Smeltzer in their inquiry concerning a possible relationship between depressive subtypes and neurobiological mechanisms of cognitive impairment. Unfortunately, there are few data addressing this question at present. Dr Dilsaver and Mr Smeltzer cite the finding by Wolfe et al<sup>1</sup>of a quantitative similarity between bipolar depressed patients and patients with Huntington's disease with respect to degree of cognitive impairment. However, Wolfe et al also point out that, with respect to patterns of response bias (ie, tendency to commit false-positive or false-negative errors), unipolar depressed patients are qualitatively similar to patients with Huntington's disease, while bipolar patients resemble controls. Cummings<sup>2</sup>has recently noted that it is the "pattern of intellectual disturbances" that best differentiates patients with subcortical dementias from those with dementias involving preponderantly the cerebral cortex. By these criteria, it would seem that unipolar depressed patients
Comparison of the 1- and 5-year effectiveness of adalimumab, etanercept and ustekinumab in patients with psoriasis in daily clinical practice: results from the prospective BioCAPTURE registry
Authors: J. Zweegers, J.M.M. Groenewoud, J.M.P.A. van den Reek, M.E. Otero, P.C.M. van de Kerkhof, R.J.B. Driessen, P.P.M. van Lümig, M.D. Njoo, P.M. Ossenkoppele, J.M. Mommers, M.I.A. Koetsier, W.P. Arnold, M.P.M. Andriessen, A.L.A. Kuijpers, M.A.M. Berends, W. Kievit, E.M.G.J. de Jong
Journal: British Journal of Dermatology (2016)

The efficacy of etanercept and ustekinumab in psoriasis has been compared in one randomized controlled trial. Comparison of the long‐term effectiveness of biologics in daily‐practice psoriasis treatment is currently lacking. To compare the effectiveness between the three widely used outpatient biologics adalimumab, etanercept and ustekinumab in daily‐practice psoriasis treatment and to correct for confounders. Data were extracted from the prospective, multicentre BioCAPTURE registry. Multilevel linear regression analyses (MLRAs) and generalized estimating equation (GEE) analyses were performed on the course of mean Psoriasis Area and Severity Index (PASI) and PASI 75 (≥ 75% reduction vs. baseline). Both models were corrected for confounders. Subgroup analyses for biological dose were performed. We included 356 patients with 513 treatment episodes: 178 adalimumab, 245 etanercept and 90 ustekinumab. MLRA showed a similar effectiveness between adalimumab, etanercept and ustekinumab after 1 year, but the highest effectiveness for ustekinumab during 5 years of treatment (P =0·047; ustekinumab vs. etanercept, P =0·019). GEE analysis revealed a higher chance of attaining PASI 75 with adalimumab and ustekinumab than with etanercept at 1 year of treatment. A higher than label dose was more often used in patients treated with etanercept (adalimumab, etanercept and ustekinumab: respectively 31·5%, 55·1% and 17% after 1 year, P <0·001; 39·3%, 71·4% and 24% after 5 years, P <0·001). Compared with etanercept, ustekinumab had the highest effectiveness during 5 years of treatment. Patients receiving adalimumab and ustekinumab more often reached PASI 75 than those on etanercept at 1 year of treatment. Dose escalation was more frequent in etanercept and adalimumab than in ustekinumab.
Final findings from a phase II, placebo-controlled, randomized discontinuation trial (RDT) of sorafenib (BAY 43–9006) in patients with advanced renal cell carcinoma (RCC)
Authors: M. J. Ratain, T. Eisen, W. M. Stadler, K. T. Flaherty, M. Gore, A. Desai, A. Patnaik, H. Q. Xiong, B. Schwartz, P. O’Dwyer
Journal: Journal of Clinical Oncology (2005)

4544 Background: BAY 43–9006 (BAY) is a Raf kinase and VEGFR inhibitor with effects on both tumor proliferation and angiogenesis. This Phase II RDT determined the effects of BAY on tumor growth in patients (pts) with stable disease (SD) after 12 wks treatment. Methods: 202 pts with advanced RCC (ECOG 1–2) entered a 12-wk induction phase (BAY 400 mg po bid). Pts with bidimensional tumor measurements remaining within 25% of baseline (SD) were then randomized (double-blind) to BAY 400 mg bid or placebo (Pb), and the progression-free rate [percentage of pts with SD or response] at 24 wks compared. Results: 65 pts with SD at 12 wks were randomized to BAY (n=32) or Pb (n=33); pt characteristics were well matched between groups. After 24 wks, 6 pts (18%) on Pb were progression-free compared with 16 pts (50%) on BAY (p=0.0077). Median progression-free survival (PFS) after randomization was greater with BAY vs Pb (23 vs 6 wks, p=0.0001, hazard ratio 0.29). BAY was restarted in 25 pts who progressed on Pb after a median time from randomization of 7 wks. Median PFS after restarting BAY in these pts was 24 wks; 13 pts are ongoing. The most common drug-related AEs in all 202 pts with RCC were rash (62%), hand-foot skin reaction (HFS; 61%) and fatigue (56%). Grade 3/4 drug-related AEs occurred in 47% of patients; the most common were hypertension (24%), HFS (13%) and fatigue (5%). Drug-related AEs led to discontinuation in 2% of pts, and no deaths. Conclusions: These Phase II data prove that BAY had a marked effect on PFS in pts with metastatic RCC, with an acceptable toxicity profile. The RDT (with design modifications to improve efficiency) should be considered for Phase II trials of other drugs with putative effects on disease stabilization. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Healthcare Bayer, CFSB, Deutsche Bank, Medacorp AstraZeneca, Bayer AG Bayer, Onyx Bayer Bayer
FGF2 Mediates Resistance In CML Patients In The Absence Of Kinase Domain Mutations, and Resistance Is Overcome By Ponatinib
Authors: Elie Traer, Nathalie Javidi-Sharifi, Anupriya Agarwal, Jennifer B Dunlap, Isabel English, Jacqueline Martinez, Jeffrey W. Tyner, Melissa Wong, Brian J. Druker
Journal: Blood (2013)
Antithrombotic Therapy in Patients With Peripheral Artery Disease
Authors: Marc P. Bonaca
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Evaluation of nilotinib (N) in advanced GIST previously treated with imatinib mesylate (IM) and sunitinib (S).
Authors: C. Cauchi, N. Somaiah, P. F. Engstrom, S. Litwin, M. Lopez, J. Lee, M. Davey, B. Bove, A. K. Godwin, M. von Mehren
Journal: Journal of Clinical Oncology (2010)

10090 Background: Patients with advanced GIST progressing following IM and S often continue with good performance statuses and need additional therapy. This study tested the benefit of N, a second generation tyrosine kinase inhibitor that functions via ATP-competitive inhibition, developed to optimize binding to BCR-ABL for the therapy of chronic myelogenous leukemia. In vitro the agent can inhibit KIT and PDGFR phosphorylation, is active against IM-resistant cell lines and achieves higher intracellular concentrations compared to IM. Methods: This was a single center open label phase II study. The primary objective was to determine PFS at 6 months. Using a novel statistical design (S. Litwin et al, 2008), 17 patients were to be enrolled; if 10 or more were progression free (PF) at 2 months an additional 19 patients would be enrolled. The therapy was considered of benefit if greater than 13 patients were PF at 6 months. All patients signed informed consents and entry criteria included normal cardiac function. Exploratory analyses correlating genotype with benefit was also performed. Results: 15 patients were consented; one patient was found to be ineligible due to a cardiac arrhythmia; a second began therapy and pathology review found a malignant fibrous tumor. Patient characteristics: median age of 63; M:F ratio of 9:4; and primary tumor site in stomach (n=6), small bowel (n=5), and colon/rectum (n=2). Two patients had received therapy beyond IM and S. Treatment was well tolerated with one grade 4 anemia attributed to N. No CRs or PRs were noted; median time on study was 2 months. One patient remains on study with stable disease for 7+ cycles. Nine tumor samples underwent mutation testing: 6 KIT exon 11 mutations, 1 KIT exon 9 mutation and 2 without KIT/PDGFR mutations. Two samples demonstrated concurrent KIT mutations; a primary exon 11 mutation with an exon 17 mutation, including the patient with prolonged stable disease. Conclusions: Nilotinib was well tolerated in these patients with advanced GIST. Accrual was halted due to insufficient clinical benefit. However, nilotinib may provide benefit to specific subsets of advanced GIST with exon 17 mutations. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
A Unique Case of Erdheim-Chester Disease With Cervical and Lumbosacral Nerve Involvement
Authors: Na Niu, Xinxin Cao, Ruixue Cui
Journal: Clinical Nuclear Medicine (2016)

Cervical and lumbosacral nerve roots and plexus involvement in Erdheim-Chester disease (ECD) is rare. A 50-year-old man with progressive edema in bilateral lower extremities, numbness, weakness, and muscle atrophy of upper limb for 2 years had been misdiagnosed of neuritis or cervical spondylosis until he presented bone pain. In addition to bilateral symmetric involvement in long bones, bilateral hypermetabolism in cervical and lumbosacral nerve roots was found by FDG PET/CT scan. ECD was diagnosed by bone biopsy. This case reported the rare peripheral neural involvement and highlighted the advantage of FDG PET/CT scan in evaluating the multisystem involvement of ECD.
Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial
Authors: Eugene R Bleecker, J Mark FitzGerald, Pascal Chanez, Alberto Papi, Steven F Weinstein, Peter Barker, Stephanie Sproule, Geoffrey Gilmartin, Magnus Aurivillius, Viktoria Werkström, Mitchell Goldman
Journal: The Lancet (2016)
EGFR exon 20 insertion mutations: Incidence and clinicopathologic characteristics in U.S. patients with lung adenocarcinoma.
Authors: Maria E. Arcila, Khedoudja Nafa, Jamie E. Chaft, Natasha Rekhtman, Maureen Frances Zakowski, Mark G. Kris, Marc Ladanyi
Journal: Journal of Clinical Oncology (2012)

10560 Background: Activating insertion mutations in exon 20 of EGFR are reported in a small subset of lung adenocarcinomas (ADC). In contrast to the classic EGFR mutations, they appear to confer primary resistance to currently approved EGFR tyrosine kinase inhibitors. Their incidence and clinicopathologic features are not well established. Methods: Lung ADCs (n=1500) were screened for major activating mutations in EGFR (exons 19 and 21) and KRAS (exon 2). Negative cases were tested for EGFR exon 20 insertions by a PCR-based sizing assay. Extended testing for additional recurrent point mutations in EGFR, KRAS, BRAF, NRAS, PIK3CA, MEK1 and AKT was performed in all cases by Sequenom mass spectrometry. A subset of cases was also tested for ALK rearrangements by FISH. Results: We identified 32cases withEGFRexon 20 insertions, accounting for 11% of all EGFR mutations. EGFRexon 20 insertions were mutually exclusive with the other genetic alterations tested except for PIK3CA mutations. The incidence was higher among never-smokers (p&lt;0.0001) but there was no association with sex, ethnic origin or stage at diagnosis. Insertions were 3, 6, 9 or 12bp; 9bp insertions were most common (50%, 16/32). Morphologically, 90% of tumors were moderate to poorly differentiated with a predominant mixed ADC phenotype. Conclusions: EGFR exon 20 testing may identify a unique subset of EGFR mutant lung ADCs which is significantly larger than previously reported, making this the third most common type of EGFR mutation after exon 19 deletions and L858R. This population could potentially benefit from alternate targeted therapies, many of which are currently in clinical development.