tbuckley/cabot-search huggingface dataset:
Dehydration activates an NF-κB–driven, COX2-dependent survival mechanism in renal medullary interstitial cells
Authors: Chuan-Ming Hao, Fiona Yull, Timothy Blackwell, Martin Kömhoff, Linda S. Davis, Matthew D. Breyer
Journal: Journal of Clinical Investigation (2000)

Renal prostaglandin (PG) synthesis is mediated by cyclooxygenase-1 and -2 (COX1 and COX2). After dehydration, the maintenance of normal renal function becomes particularly dependent upon PG synthesis. The present studies were designed to examine the potential link between medullary COX1 and COX2 expression in hypertonic stress. In response to water deprivation, COX2, but not COX1, mRNA levels increase significantly in the renal medulla, specifically in renal medullary interstitial cells (RMICs). Water deprivation also increases renal NF-κB–driven reporter expression in transgenic mice. NF-κB activity and COX2 expression could be induced in cultured RMICs with hypertonic sodium chloride and mannitol, but not urea. RMIC COX2 expression was also induced by driving NF-κB activation with a constitutively active IκB kinase α (IKKα). Conversely, introduction of a dominant-negative IκB mutant reduced COX2 expression after hypertonicity or IKKα induction. RMICs failed to survive hypertonicity when COX2 was downregulated using a COX2-selective antisense or blocked with the selective nonsteroidal anti-inflammatory drug (NSAID) SC58236, reagents that did not affect cell survival in isotonic media. In rabbits treated with SC58236, water deprivation induced apoptosis of medullary interstitial cells in the renal papilla. These results demonstrate that water deprivation and hypertonicity activate NF-κB. The consequent increase in COX2 expression favors RMIC survival in hypertonic conditions. Inhibition of RMIC COX2 could contribute to NSAID-induced papillary injury.
THE EFFECTS OF ALTERED ARTERIAL TENSIONS OF CARBON DIOXIDE AND OXYGEN ON CEREBRAL BLOOD FLOW AND CEREBRAL OXYGEN CONSUMPTION OF NORMAL YOUNG MEN 1
Authors: Seymour S. Kety, Carl F. Schmidt
Journal: Journal of Clinical Investigation (1948)

5 11.4 7.38 7.33 7.30 7.28 T. L. 49.4 51.7 55.7 57.2 42 47 53 54 15.7 15.0 9.6 10.7 7.38 7.36 7.33 7.33 R.Ro.47.3 50.7 55.1 55.0 41 48 53 56 16.5 16.6 9.6 11.4 7.38 7.34 7.32 7.30 W. S. 51.5 53.2 57.1 57.4 48 54 60 60 16.5 16.8 10.7 12.7 7.35 7.31 7.29 7.28 D. M. 48.3 50.4 54.6 55.1 41 46 50 51 18.6 18.5 12.6 14.0 7.40 7.36 7.35 7.33 R. S. 48.5 52.0 53.8 54.8 42 53 54 58 14.8 15.5 9.8 12.3 7.37 7.30 7.30 7.27.7% C02 J. B. 51.7 55.6 57.7 58.6 45 60 58 66 18.2 18.4 11.9 16.0 7.38 7.28 7.31 7.26 W. H. 52.5 56.9 58.8 59.5 45 58 52 59 18.3 18.7 12.1 16.0 7.40 7.32 7.35 7.31 Mean 49.5 52.5* 55.9 56.5* 43 52* 54 58* 16.8 16.9 10.7 13.0* 7.38 7.33* 7.32 7.30 85-100% 02J. E. 48.2 47.9 55.3 55.7 39 37 48 48 17.8 19.1 10.8 11.1 7.42 7.45 7.38 7.38 T. L. 50.1 50.8 58.0 59.1 41 40 51 56 15.5 16.7 7.6 8.3 7.41 7.42 7.36 7.34 S. H. 51.0 49.3 55.8 55.1 43 41 51 50 16.5 17.6 16.6 12.2 7.39 7.40 7.33 7.34 R. Re. 51.1 50.9 56.7 57.4 42 42 52 53 16.1 17.5 10.8 10.9 7.40 7.40 7.34 7.34 J. B. 49.3 49.5 55.6 56.7 43 43 53 54 16.2 17.8 10.5 11.2 7.38 7.39 7.32 7.32 M. H. 51.4 51.6 57.5 58.7 42 42 52 53 17.2 19.0 11.2 11.5 7.41 7.41 7.36 7.35 Mean 50.2 50.0 56.5 57.1 42 41 51 52 16.6 18.0* 10.4 10.9* 7.40 7.41 7.35 7.35 10% 02 R. S. 47.7 48.2 52.4 50.9 41 38 49 43 16.1 9.7 11.1 6.4 7.38 7.41 7.33 7.39 S. H. 50.6 50.9 55.5 53.9 41 37 48 43 17.0 11.0 11.8 7.0 7.42 7.46 7.37 7.41 K. T. 45.4 44.9 53.0 48.9 35 31 46 33 17.8 11.6 10.8 7.8 7.45 7.50 7.38 7.68 W. H. 50.7 49.7 57.1 54.6 42 36 51 44 18.7 13.1 12.4 7.6 7.41 7.48 7.36 7.41 D. M. 46.8 45.9 54.5 51.5 40 34 51 42 19.4 13.2 12.5 8.0 7.40 7.47 7.34 7.41 M. H. 49.1 49.0 56.2 53.4 42 37 51 45 17.7 11.2 10.7 6.5 7.39 7.43 7.34 7.40 J. E. 47.0 46.6 54.5 51.5 39 36 51 43 19.0 12.3 10.8 7.5 7.40 7.45 7.34 7.38 Mean 48.2 47.9 54.7 52.1* 40 36* 50 41 18.0 11.7* 11.4 7.3* 7.41 7.46* 7.35 7.41* Hyperventilation active and passive Mean 50.1 41.7* 55.9 52.5* 45 26* 52 38* 17.9 18.6* 11.3 7.8* 7.38 7.54* 7.35 7.48* * Indicates statistically significant changes.t C = Control period, room air tensions of 02 and CO2.t E = Experimental period, special gas mixture.
Weight, Adiposity, and Physical Activity as Determinants of an Insulin Sensitivity Index in Pima Indian Children
Authors: Joy C. Bunt, Arline D. Salbe, Inge T. Harper, Robert L. Hanson, P. Antonio Tataranni
Journal: Diabetes Care (2003)

OBJECTIVE—To determine whether measures of physical activity are related to an insulin sensitivity index ([ISI] 104/fasting insulin × glucose) independent of weight or adiposity in children. RESEARCH DESIGN AND METHODS—We conducted a longitudinal study of 90 Pima Indian children (39 boys and 51 girls) at 5 and 10 years of age measuring adiposity (dual-energy X-ray absorptiometry), physical activity behavior (questionnaire: number of activities per week [ACT], average hours per week [TIME]), and energy expenditure (doubly labeled water: physical activity level [PAL]). RESULTS—In cross-sectional analyses, ACT was correlated with ISI at 5 years of age (r = 0.24, P = 0.02) and at 10 years of age (r = 0.21, P = 0.05), but these relationships were not independent of weight or adiposity. PAL was correlated with ISI at 10 years of age (r = 0.39, P = 0.03) but was not independent of weight or adiposity. Longitudinally, ISI decreased from 5 to 10 years of age, and increases in weight and adiposity were associated with decreases in ISI (r = −0.51 and −0.41, respectively; both P &amp;lt; 0.0001). ACT decreased from 5 to 10 years of age, but children who had smaller decreases in ACT had smaller decreases in ISI, independent of increases in weight or adiposity (partial r = 0.22, P = 0.04 adjusted for either weight or adiposity). CONCLUSIONS—These data suggest that early establishment and maintenance of an active lifestyle can have a beneficial effect on ISI that is partially independent of changes in weight or adiposity. This is particularly relevant considering the current epidemics of both obesity and type 2 diabetes in children.
Paclitaxel/carboplatin/etoposide (PCE) therapy for advanced poorly differentiated neuroendocrine (PDNE) carcinoma: A Minnie Pearl Cancer Research Network phase II trial
Authors: F. T. Miranda, D. R. Spigel, J. D. Hainsworth, D. S. Thompson, D. A. Yardley, H. A. Burris, S. Litchy, M. Shrader, J. K. Hon, S. W. Corso, F. A. Greco
Journal: Journal of Clinical Oncology (2005)

4058 Background: PDNE carcinoma may arise from a variety of primary sites or present as an unknown primary. PDNE tumors have historically been sensitive to platinum/etoposide-based chemotherapy, as opposed to very poor activity in well differentiated neuroendocrine tumors. This phase II trial expands our experience with PCE in the treatment of patients (pts) with PDNE carcinoma. The objectives were to determine the objective response rate and survival. Methods: Eligibility requirements: small cell carcinoma (except small cell lung cancer) or poorly differentiated carcinoma (PDC) with diagnostic IP staining or electron microscopy; unknown or known primary; metastatic or locally advanced tumor; well differentiated carcinoid-type tumors excluded; ECOG PS 0–2; no previous chemotherapy; measurable disease; adequate organ function; informed consent. Pts received P 200mg/m2 IV, day 1; C AUC 6.0 IV, day 1; E 50/100mg po alternating, days 1–10; (repeated q 21 days x 4 courses). Local radiotherapy was subsequently administered to patients with advanced local tumor. Responding/stable pts received P 70mg/m2 IV, 6 of 8 weeks, for 24 weeks. Results: Between 1/99 and 11/04, 66 pts were treated. Pt characteristics: median age 58 years; male/female, 40/26 [small cell (12 pts); PDC (54 pts)]; primary site known/unknown, 27/39; visceral metastases, 51 pts (77%); ≥ 2 metastatic sites, 44 pts (66%). 59 pts were evaluable for response: complete, 9 pts (15%); partial, 24 pts (40%); stable/minor, 21 pts (35%); progression, 5 pts (10%). Median response duration was 9 months. After a median follow-up of 32 months, median survival is 14.8 months, with 1-, 2-, 3-, 4-, and 5-year survivals of 57%, 34%, 23%, 15%, and 15%, respectively. There was no difference (p=0.43 log rank) in survival comparing pts with known to unknown primary (median 15.6 vs. 13.8 and 1-, 2-year survivals 58%, 39% vs. 55%, 30%, respectively). Grade 3/4 toxicity was predominantly myelosuppression. Conclusions: PCE is active against PDNE and produces clinical benefit and prolongation of survival. A minority of pts remain alive, some progression-free, for several years. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Phase Ii Multi-Institutional Prospective Randomized Trial Comparing S-1 + Paclitaxel with Paclitaxel Alone As Second-Line Chemotherapy in Patients with Recurrent Gastric Cancer Prior to S-1 Treatment (Ccog 0701)
Authors: K. Nakanishi, D. Kobayashi, Y. Mochizuki, K. Ishigure, S. Ito, H. Kojima, A. Ishiyama, S. Fujitake, T. Shikano, Y. Kodera
Journal: Annals of Oncology (2014)
U.S. Food and Drug Administration Approval: Obinutuzumab in Combination with Chlorambucil for the Treatment of Previously Untreated Chronic Lymphocytic Leukemia
Authors: Hyon-Zu Lee, Barry W. Miller, Virginia E. Kwitkowski, Stacey Ricci, Pedro DelValle, Haleh Saber, Joseph Grillo, Julie Bullock, Jeffry Florian, Nitin Mehrotra, Chia-Wen Ko, Lei Nie, Marjorie Shapiro, Mate Tolnay, Robert C. Kane, Edvardas Kaminskas, Robert Justice, Ann T. Farrell, Richard Pazdur
Journal: Clinical Cancer Research (2014)

On November 1, 2013, the U.S. Food and Drug Administration (FDA) approved obinutuzumab (GAZYVA; Genentech, Inc.), a CD20-directed cytolytic antibody, for use in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL). In stage 1 of the trial supporting approval, patients with previously untreated CD20-positive CLL were randomly allocated (2:2:1) to obinutuzumab + chlorambucil (GClb, n = 238), rituximab + chlorambucil (RClb, n = 233), or chlorambucil alone (Clb, n = 118). The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall response rate (ORR). Only the comparison of GClb to Clb was relevant to this approval and is described herein. A clinically meaningful and statistically significant improvement in PFS with medians of 23.0 and 11.1 months was observed in the GClb and Clb arms, respectively (HR, 0.16; 95% CI, 0.11-0.24; P < 0.0001, log-rank test). The ORRs were 75.9% and 32.1% in the GClb and Clb arms, respectively, and the complete response rates were 27.8% and 0.9% in the GClb and Clb arms, respectively. The most common adverse reactions (≥10%) reported in the GClb arm were infusion reactions, neutropenia, thrombocytopenia, anemia, pyrexia, cough, and musculoskeletal disorders. Obinutuzumab was the first Breakthrough Therapy-designated drug to receive FDA approval.
Effects of Insulin-like Growth Factor Binding Protein-3 and Farnesyltransferase Inhibitor SCH66336 on Akt Expression and Apoptosis in Non-Small-Cell Lung Cancer Cells
Authors: H.-Y. Lee, H. Moon, K.-H. Chun, Y.-S. Chang, K. Hassan, L. Ji, R. Lotan, F. R. Khuri, W. K. Hong
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Overexpression of insulin-like growth factor binding protein-3 (IGFBP-3) induces apoptosis in non–small-cell lung cancer (NSCLC) cells in vitro and in vivo . However, Ras-mediated signaling pathways could develop resistance to apoptotic activities of IGFBP-3 in NSCLC cells. We thus evaluated the therapeutic potential of the combination of IGFBP-3 and SCH66336, a farnesyltransferase inhibitor that blocks Ras activation, in NSCLC cell lines. Methods: The effects of the combination of adenoviral IGFBP-3 (Ad-IGFBP3) and SCH66336 on proliferation and apoptosis of NSCLC cell lines (H1299, H596, A549, H460, H358, H322, and H226B) were assessed in vitro and in vivo by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a flow cytometry–based terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay, western blot analyses, and an NSCLC xenograft tumor model. The specific effects of Ad-IGFBP 3 and SCH66336 on mitogen-activated protein kinase and Akt were assessed by using adenoviral vectors that express constitutively active MEK1 or constitutively active Akt. Synergy was assessed by median effect analysis. Results: The combination of Ad-IGFBP3 and SCH66336 had synergistic antiproliferative effects in five cell lines (H1299, H596, A549, H460, and H322). Antiproliferative effects were accompanied by increased apoptosis in H460 cells in vitro . Overexpression of a constitutively active Akt but not a constitutively active MEK-1 rescued H460 cells from apoptosis induced by single or combined treatment of Ad-IGFBP3 and SCH66336. In H1299 tumor xenografts, Ad-IGFBP3 and SCH66336 was associated with decreased tumor volume, increased apoptosis, and decreased Akt levels. Conclusions: The combination of Ad-IGFBP3 and SCH66336 decreased Akt expression and increased apoptosis in NSCLC cells in vitro and in vivo . Simultaneous treatment with IGFBP-3 and SCH66336 may have the potential to be an effective therapeutic strategy in NSCLC.
TCT-574 First Randomized Evaluation of the Extent of Neointimal Formation between Two Types of Sirolimus-Eluting Stents with Different Designs on Biodegradable Polymer Coatings: The BuMA-OCT Trial
Authors: Yuejin Yang, Hongbing Yan, Zhongwei Sun, Yelin Zhao, Yida Tang, Zhan Gao, Jue Chen, Jingang Cui, Bo Xu
Journal: Journal of the American College of Cardiology (2013)
5-hydroxytryptamine strongly inhibits fluid secretion in guinea pig pancreatic duct cells
Authors: Atsushi Suzuki, Satoru Naruse, Motoji Kitagawa, Hiroshi Ishiguro, Toshiyuki Yoshikawa, Shigeru B.H. Ko, Akiko Yamamoto, Hiroyuki Hamada, Tetsuo Hayakawa
Journal: Journal of Clinical Investigation (2001)

We studied the distribution of 5-hydroxytryptamine– (5-HT-) containing cells in the guinea pig pancreas and examined the effects of 5-HT on fluid secretion by interlobular pancreatic ducts. The 5-HT–immunoreactive cells with morphological characteristics of enterochromaffin (EC) cells were scattered throughout the duct system and were enriched in islets of Langerhans. The fluid secretory rate in the isolated interlobular ducts was measured by videomicroscopy. Basolateral applications of 5-HT strongly but reversibly reduced HCO3-dependent, as well as secretin- and acetylcholine- (ACh-) stimulated, fluid secretion, whereas 5-HT applied into the lumen had no such effects. Secretin-stimulated fluid secretion could be inhibited by a 5-HT3 receptor agonist, but not by agonists of the 5-HT1, 5-HT2, or 5-HT4 receptors. Under the stimulation with secretin, 5-HT decreased the intracellular pH (pHi) and reduced the rate of pHi recovery after acid loading with NH4+, suggesting that 5-HT inhibits the intracellular accumulation of HCO3–. The elevation of intraductal pressure in vivo reduced secretin-stimulated fluid secretion, an effect that could be attenuated by a 5-HT3 receptor antagonist. Thus, 5-HT, acting through basolateral 5-HT3 receptors, strongly inhibits spontaneous, secretin-, and ACh-stimulated fluid secretion by guinea pig pancreatic ducts. 5-HT released from pancreatic ductal EC cells on elevation of the intraductal pressure may regulate fluid secretion of neighboring duct cells in a paracrine fashion.
Evolution of the Nitric Oxide Synthase Family in Metazoans
Authors: N. Andreakis, S. D'Aniello, R. Albalat, F. P. Patti, J. Garcia-Fernandez, G. Procaccini, P. Sordino, A. Palumbo
Journal: Molecular Biology and Evolution (2010)

Nitric oxide (NO) is essential to many physiological functions and operates in several signaling pathways. It is not understood how and when the different isoforms of nitric oxide synthase (NOS), the enzyme responsible for NO production, evolved in metazoans. This study investigates the number and structure of metazoan NOS enzymes by genome data mining and direct cloning of Nos genes from the lamprey. In total, 181 NOS proteins are analyzed from 33 invertebrate and 63 vertebrate species. Comparisons among protein and gene structures, combined with phylogenetic and syntenic studies, provide novel insights into how NOS isoforms arose and diverged. Protein domains and gene organization—that is, intron positions and phases—of animal NOS are remarkably conserved across all lineages, even in fast-evolving species. Phylogenetic and syntenic analyses support the view that a proto-NOS isoform was recurrently duplicated in different lineages, acquiring new structural configurations through gains and losses of protein motifs. We propose that in vertebrates a first duplication took place after the agnathan–gnathostome split followed by a paralog loss. A second duplication occurred during early tetrapod evolution, giving rise to the three isoforms—I, II, and III—in current mammals. Overall, NOS family evolution was the result of multiple gene and genome duplication events together with changes in protein architecture.
Guns, Fear, the Constitution, and the Public's Health
Authors: Garen J. Wintemute
Journal: New England Journal of Medicine (2008)

On March 18, the Supreme Court heard oral arguments in the case of District of Columbia v. Heller, a case challenging handgun control statutes adopted in 1976. Dr. Garen Wintemute argues that the overturning of gun control statutes could weaken the framework of ordered liberty that makes civil society possible.
The S100A7-c-Jun Activation Domain Binding Protein 1 Pathway Enhances Prosurvival Pathways in Breast Cancer
Authors: Ethan D. Emberley, Yulian Niu, Linda Curtis, Sandra Troup, Sanat K. Mandal, Jeffery N. Myers, Spencer B. Gibson, Leigh C. Murphy, Peter H. Watson
Journal: Cancer Research (2005)

S100A7 is among the most highly expressed genes in preinvasive breast cancer, is a marker of poor survival when expressed in invasive disease, and promotes breast tumor progression in experimental models. To explore the mechanism of action, we examined the role of S100A7 in cell survival and found that overexpression of S100A7 in MDA-MB-231 cell lines promotes survival under conditions of anchorage-independent growth. This effect is paralleled by increased activity of nuclear factor-kappaB (3-fold) and phospho-Akt (4-fold), which are known to mediate prosurvival pathways. S100A7 and phospho-Akt are also correlated in breast tumors examined by immunohistochemistry (n = 142; P < 0.0001; r = 0.34). To explore the underlying mechanism, we examined the role of a putative c-Jun activation domain-binding protein 1 (Jab1)-binding domain within S100A7 using a panel of MDA-MB-231 breast cell lines stably transfected with either S100A7 or S100A7 mutated at the Jab1 domain. Structural analysis by three-dimensional protein modeling, immunoprecipitation, and yeast two-hybrid assay and functional analysis using transfected reporter gene and Western blot assays revealed that the in vitro effects of S100A7 on phospho-Akt and the nuclear factor-kappaB pathway are dependent on the Jab1-binding site and the interaction with Jab1. Enhanced epidermal growth factor receptor signaling was also found to correlate with the increased phospho-Akt. Furthermore, the Jab1-binding domain is also necessary for the enhanced tumorigenicity conferred by S100A7 expression in murine xenograft tumors in vivo. We conclude that the S100A7-Jab1 pathway acts to enhance survival under conditions of cellular stress, such as anoikis, which may promote progression of breast cancer.
RhoGEF12 controls cardiac remodeling by integrating G protein– and integrin-dependent signaling cascades
Authors: Mikito Takefuji, Marcus Krüger, Kishor K. Sivaraj, Kozo Kaibuchi, Stefan Offermanns, Nina Wettschureck
Journal: The Journal of Experimental Medicine (2013)

Structural cardiac remodeling, including hypertrophy and fibrosis, plays a crucial role in the pathogenesis of heart failure. In vitro studies suggested a role of the small GTPase RhoA in hypertrophic cardiomyocyte growth, but neither the molecular mechanisms leading to RhoA activation nor their relevance in vivo are known. We use here a mass spectrometric approach to identify Rho guanine nucleotide exchange factors (RhoGEFs) activated during cardiac pressure overload in vivo and show that RhoGEF12 is a central player during cardiac remodeling. We show that RhoGEF12 is required for stretch-induced RhoA activation and hypertrophic gene transcription in vitro and that its activation depends on integrin β1 and heterotrimeric G proteins of the G12/13 family. In vivo, cardiomyocyte-specific deletion of RhoGEF12 protects mice from overload-induced hypertrophy, fibrosis, and development of heart failure. Importantly, in mice with preexisting hypertrophy, induction of RhoGEF12 deficiency protects from cardiac decompensation, resulting in significantly increased long-term survival. Collectively, RhoGEF12 acts as an integrator of stretch-induced signaling cascades in cardiomyocytes and is an interesting new target for therapeutic intervention in patients with pressure overload-induced heart failure.
A mixed treatment comparison of the efficacy of anti-TNF agents in rheumatoid arthritis for methotrexate non-responders demonstrates differences between treatments: a Bayesian approach
Authors: Susanne Schmitz, Roisin Adams, Cathal D Walsh, Michael Barry, Oliver FitzGerald
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> A number of tumour necrosis factor α (TNFα) antagonists (anti-TNFα) are available to treat rheumatoid arthritis. All of these have demonstrated considerable efficacy in placebo controlled trials, but few head-to-head comparisons exist to date. This work9s objective is to estimate the relative efficacy among licensed anti-TNFs in patients who have had an inadequate response to methotrexate (MTX). Different outcome measures are used to highlight the advantages of continuous measures in such analyses. <h3>Methods</h3> A systematic review identified randomised controlled trials comparing the efficacy of licensed anti-TNFα agents with placebo at 24 weeks in patients who have had an inadequate response to MTX. Relative efficacy was estimated using Bayesian mixed treatment comparison (MTC) models. Three different outcome measures were used: RR of achieving an American College of Rheumatology (ACR) 20 and ACR50 response and the percentage improvement in Health Assessment Questionnaire (HAQ) score. <h3>Results</h3> 16 published trials were included in the analysis. All anti-TNFs show considerably improved efficacy over placebo. The MTC results also provide evidence of some differences in efficacy of the TNFα antagonists. Etanercept appears superior to infliximab and golimumab, and certolizumab to infliximab and adalimumab. ACR results indicate improved efficacy of certolizumab over golimumab. On HAQ analysis, adalimumab, certolizumab, etanercept and golimumab appear superior to infliximab, and etanercept shows improved efficacy compared with adalimumab. <h3>Conclusions</h3> There are differences in efficacy among the TNFα antagonists. In a MTC, a continuous outcome measure has more strength to detect such differences than a binomial outcome measure because of its enhanced sensitivity to change.