tbuckley/cabot-search huggingface dataset:
Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan: a 12-week, randomised, double-blind, placebo-controlled phase IIb study
Authors: Tsutomu Takeuchi, Yoshiya Tanaka, Manabu Iwasaki, Hiroaki Ishikura, Satoshi Saeki, Yuichiro Kaneko
Journal: Annals of the Rheumatic Diseases (2015)

Objective To evaluate the efficacy, safety and dose response of a novel oral Janus kinase inhibitor, peficitinib (ASP015K), as monotherapy in Japanese patients with moderate to severe rheumatoid arthritis (RA). Methods In a 12-week, double-blind study, 281 adult patients with RA with active disease not on concomitant disease-modifying antirheumatic drug therapy were randomised equally to once-daily placebo or peficitinib 25, 50, 100 and 150 mg. The primary endpoint was American College of Rheumatology (ACR) 20 response in the peficitinib treatment groups versus placebo at week 12. Results Mean age was 53.0 years, 81.1% were female and 25.3% had previously used antitumour necrosis factor therapy. Peficitinib 50, 100 and 150 mg each showed statistically significantly higher ACR20 response rates compared with placebo, and response rates increased up to 150 mg with a statistically significant dose response. The total incidence of treatment-emergent adverse events (TEAEs) was similar between the placebo (64.3%) and peficitinib 25, 50, 100 and 150 mg groups (70.9%, 64.9%, 52.7% and 67.2%, respectively). TEAEs occurring more frequently in the peficitinib group compared with the placebo group included nasopharyngitis, increased blood creatine phosphokinase and diarrhoea. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in peficitinib 25 and 100 mg). Conclusions Treatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed acceptable safety profile. These findings support further developments of peficitinib for RA treatment. Trial registration number NCT01649999; Results.
Autophagy in the CNS and Periphery Coordinate Lipophagy and Lipolysis in the Brown Adipose Tissue and Liver
Authors: Nuria Martinez-Lopez, Marina Garcia-Macia, Srabani Sahu, Diana Athonvarangkul, Emily Liebling, Paola Merlo, Francesco Cecconi, Gary J. Schwartz, Rajat Singh
Journal: Cell Metabolism (2015)
Comparing Contemporary Surgery to External-Beam Radiotherapy for Clinically Localized Prostate Cancer
Authors: Michael J. Zelefsky, Steven A. Leibel
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.16.3363 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12177094 Comparing Contemporary Surgery to External-Beam Radiotherapy for Clinically Localized Prostate Cancer Michael J. ZelefskyxMichael J. ZelefskySearch for articles by this author , Steven A. LeibelxSteven A. LeibelSearch for articles by this author Show More Memorial Sloan-Kettering Cancer Center, New York, NY https://doi.org/10.1200/JCO.2002.20.16.3363 Full Text PDF Figures and Tables "Comparing Contemporary Surgery to External-Beam Radiotherapy for Clinically Localized Prostate Cancer." Journal of Clinical Oncology, 20(16), pp. 3363–3364© 2002 by American Society of Clinical Oncology
Risk for septic arthritis was increased in adults with incident diagnosis of gout
Authors: Dennis G. Maki
Journal: Annals of Internal Medicine (2015)

ACP Journal Club15 December 2015Risk for septic arthritis was increased in adults with incident diagnosis of goutDennis G. Maki, MD, MACPDennis G. Maki, MD, MACPUniversity of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA (D.G.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2015-163-12-012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationLim SY, Lu N, Choi HK. Septic arthritis in gout patients: a population-based cohort study. Rheumatology (Oxford). 2015 Jul 12. [Epub ahead of print] https://pubmed.ncbi.nlm.nih.gov/26170377Clinical Impact RatingsGIM/FP/GP: Geriatrics: Rheumatology: References1. Ma L, Cranney A, Holroyd-Leduc JM. Acute monoarthritis: what is the cause of my patient's painful swollen joint? CMAJ. 2009;180:59-65. [PMID: 19124791] Google Scholar2. Margaretten ME, Kohlwes J, Moore D, Bent S. Does this adult patient have septic arthritis? JAMA. 2007;297:1478-88. [PMID: 17405973] Google Scholar3. Lenski M, Scherer MA. Analysis of synovial inflammatory markers to differ infectious from gouty arthritis. Clin Biochem. 2014;47:49-55. [PMID: 24177196] Google Scholar4. Gordon C, Swan A, Dieppe P. Detection of crystals in synovial fluids by light microscopy: sensitivity and reliability. Ann Rheum Dis. 1989;48:737-42. [PMID: 2478085] Google Scholar5. Papanicolas LE, Hakendorf P, Gordon DL. Concomitant septic arthritis in crystal monoarthritis. J Rheumatol. 2012;39:157-60. [PMID: 22133623] Google Scholar6. Kim H, Kim J, Ihm C. The usefulness of multiplex PCR for the identification of bacteria in joint infection. J Clin Lab Anal. 2010;24:175-81. [PMID: 20486199] Google Scholar Author, Article, and Disclosure InformationAuthors: Dennis G. Maki, MD, MACPAffiliations: University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA (D.G.M.)This article was published at Annals.org on 1 December 2015. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMortality of septic knee arthritis in Korea: risk factors analysis of a large national database 15 December 2015Volume 163, Issue 12 Page: JC12 Keywords Arthritis Databases Gout Inflammatory arthritis Polymerase chain reaction Psoriatic arthritis Rheumatoid arthritis Rheumatology Ribosomal RNA Synovial fluid ePublished: 15 December 2015 Issue Published: 15 December 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effectiveness of the parent-mediated intervention for children with autism spectrum disorder in south Asia in India and Pakistan (PASS): a randomised controlled trial
Authors: Atif Rahman, Gauri Divan, Syed Usman Hamdani, Vivek Vajaratkar, Carol Taylor, Kathy Leadbitter, Catherine Aldred, Ayesha Minhas, Percy Cardozo, Richard Emsley, Vikram Patel, Jonathan Green
Journal: The Lancet Psychiatry (2015)
Classification of PFT data using global lung initiative (GLI) and national health and nutrition examination survey (NHANES-III) models when extrapolated beyond the NHANES-III limit of 80 years of age
Authors: Olinto Linares, Dave Collingridge, Stacy Bamberg, Denitza Blagev, Steve Howe, Robert Jensen, John Hankinson, Alan Morris
Journal: European Respiratory Journal (2013)

RATIONALE: The National Health and Nutrition Examination Survey-III (NHANES-III) equations provide predicted normal values (Pred) and lower limits of normal (LLN) for patients up to 80 years of age. Extrapolation beyond 80 years can yield physiologically impossible predictions (a short older person may have negative LLN). The Global Lung Initiative (GLI-2012) prediction equations extend to 95 years.  METHODS: We used clinical spirometry data from Intermountain Medical Center and LDS Hospital patients (Salt Lake City, Utah) from 2001-2012. We analyzed data from 80-95 year old Caucasian patients. We used the NHANESIII (Hankinson et al. 1999) and the GLI-12 predictions (Quanjer et al. 2012) to calculate the Pred and LLN for FEV1, FVC, and FEV1/FVC. We compared the categorization of clinical spirometry data for NHANES-III and GLI-12.  RESULTS: We studied 1,699 spirograms from 80-95 year old Caucasian patients (1107 males, mean age 84.4, SD 2.98 and 592 females, mean 84.67, SD 3.11). Pred and LLN values were similar for both NHANES-III and GLI-12. Differences appear gender and height dependent. For FEV1/FVC, the GLI values (vary with height) appear non-linear while the NHANES-III values appear linear (height invariant). We observed differences in normal/abnormal patient categorizations for FEV1, FVC, and FEV1/FVC when comparing NHANES-III and GLI equations. the largest was 18% different categorization for FVC.  CONCLUSION: We observed differences between NHANES-III and GLI-12 categorization, with GLI-12 equations categorizing 18% more normal FVCs than NHANESIII for 80-95 yr olds.
Tumor and systemic immune responses to preoperative (pre-op) cryoablation (cryo) plus immune therapy with ipilimumab (ipi) in early-stage breast cancer (ESBC).
Authors: David B. Page, Jianda Yuan, Arielle Ginsberg, Zhiwan Dong, Phillip Wong, Ryan Emerson, Janice S. Sung, Christopher Comstock, Stephen Barnett Solomon, Virgilio Sacchini, Monica Morrow, Edi Brogi, Elizabeth Ann Morris, Sujata Patil, Harlan Robins, Jedd D. Wolchok, Clifford A. Hudis, Larry Norton, James Patrick Allison, Heather L. McArthur
Journal: Journal of Clinical Oncology (2014)

64 Background: In mice, tumor cryo plus immunologic checkpoint blockade generates tumor antigen release, proliferation of tumor-specific T-cells, and enhanced survival. We previously demonstrated in a pilot study that pre-op cryo+ipi is well tolerated in women with ESBC and did not delay standard of care surgical resection. Here, we analyze pilot study tissue and blood to explore immune response. Methods: 18 ESBC patients (pts) were treated with preop cryo (n=6), single-dose ipi 10mg/kg (n=6), or cryo+ipi (n=6). As a potential surrogate for tumor immunogenicity, baseline T-cell tumor infiltrating lymphocyte (TIL) density was evaluated by T-cell receptor quantitative DNA sequencing. We explored the systemic immune response to cryo and/or ipi using previously described laboratory measures including inducible costimulator (ICOS, a marker of activated CD4+ T-cells) and plasma interferon gamma (IFNγ, a cytokine associated with T-cell activity). Results: Of the 18 study pts, 13 pts had hormone receptor-positive (HR+) disease, 2 pts had HER2+ disease (both treated with ipi alone) and 3 pts had triple-negative (TN) disease (1 ipi alone and 2 cryo/ipi). Baseline TIL density was highly variable overall (range 2-30%), but higher in HER2+ and TN pts (median 15%) compared with HR+ pts (median 5%). Sustained &gt;2-fold elevations in ICOS and IFNγ were observed in the majority of cryo+ipi pts 30 days following treatment (ICOS: 5/6 pts; IFNγ: 4/6 pts), but in the minority of ipi pts (ICOS: 2/6 pts; IFNγ: 2/6 pts) or cryo pts (ICOS: 0/6 pts; IFNγ: 0/6 pts). Sustained ICOS and IFNγ elevations were observed regardless of baseline TIL density. Conclusions: Cryo+ipi was more likely to induce systemic immune activation compared to cryo or ipi alone. These potentially beneficial immune effects were observed in both HR+ and HR- subtypes, as well as in tumors with low or high baseline TIL density. These data support further studies of cryo+ipi in ESBC across HR+ and HR- subtypes, as well as in tumors that do not appear immunogenic at baseline.
Update on the American Board of Internal Medicine Maintenance of Certification Program
Authors: Henry H. Ting, Eric R. Bates, Mary Ellen Beliveau, Joseph P. Drozda, John Gordon Harold, Harlan M. Krumholz, Rick A. Nishimura, William J. Oetgen, Janice B. Sibley, James E. Tcheng
Journal: Journal of the American College of Cardiology (2014)
Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline
Authors: Heike A. Bischoff-Ferrari, Bess Dawson-Hughes, E. John Orav, Hannes B. Staehelin, Otto W. Meyer, Robert Theiler, Walter Dick, Walter C. Willett, Andreas Egli
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> Vitamin D deficiency has been associated with poor physical performance. <h3>Objective</h3> To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline. <h3>Design, Setting, and Participants</h3> One-year, double-blind, randomized clinical trial conducted in Zurich, Switzerland. The screening phase was December 1, 2009, to May 31, 2010, and the last study visit was in May 2011. The dates of our analysis were June 15, 2012, to October 10, 2015. Participants were 200 community-dwelling men and women 70 years and older with a prior fall. <h3>Interventions</h3> Three study groups with monthly treatments, including a low-dose control group receiving 24 000 IU of vitamin D<sub>3</sub>(24 000 IU group), a group receiving 60 000 IU of vitamin D<sub>3</sub>(60 000 IU group), and a group receiving 24 000 IU of vitamin D<sub>3</sub>plus 300 μg of calcifediol (24 000 IU plus calcifediol group). <h3>Main Outcomes and Measures</h3> The primary end point was improving lower extremity function (on the Short Physical Performance Battery) and achieving 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months. A secondary end point was monthly reported falls. Analyses were adjusted for age, sex, and body mass index. <h3>Results</h3> The study cohort comprised 200 participants (men and women ≥70 years with a prior fall). Their mean age was 78 years, 67.0% (134 of 200) were female, and 58.0% (116 of 200) were vitamin D deficient (&lt;20 ng/mL) at baseline. Intent-to-treat analyses showed that, while 60 000 IU and 24 000 IU plus calcifediol were more likely than 24 000 IU to result in 25-hydroxyvitamin D levels of at least 30 ng/mL (<i>P</i> = .001), they were not more effective in improving lower extremity function, which did not differ among the treatment groups (<i>P</i> = .26). However, over the 12-month follow-up, the incidence of falls differed significantly among the treatment groups, with higher incidences in the 60 000 IU group (66.9%; 95% CI, 54.4% to 77.5%) and the 24 000 IU plus calcifediol group (66.1%; 95% CI, 53.5%-76.8%) group compared with the 24 000 IU group (47.9%; 95% CI, 35.8%-60.3%) (<i>P</i> = .048). Consistent with the incidence of falls, the mean number of falls differed marginally by treatment group. The 60 000 IU group (mean, 1.47) and the 24 000 IU plus calcifediol group (mean, 1.24) had higher mean numbers of falls compared with the 24 000 IU group (mean, 0.94) (<i>P</i> = .09). <h3>Conclusions and Relevance</h3> Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D, they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24 000 IU. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01017354
Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174 000 participants in 27 randomised trials
Authors: Jordan Fulcher, Rachel O'Connell, Merryn Voysey, Jonathan Emberson, Lisa Blackwell, Borislava Mihaylova, John Simes, Rory Collins, Adrienne Kirby, Helen Colhoun, Eugene Braunwald, John La Rosa, T R Pedersen, Andrew Tonkin, Barry Davis, Peter Sleight, Maria Grazia Franzosi, Colin Baigent, Anthony Keech
Journal: The Lancet (2015)
Prospective Validation of Pooled Prognostic Factors in Women with Advanced Cervical Cancer Treated with Chemotherapy with/without Bevacizumab: NRG Oncology/GOG Study
Authors: Krishnansu S. Tewari, Michael W. Sill, Bradley J. Monk, Richard T. Penson, Harry J. Long, Andrés Poveda, Lisa M. Landrum, Mario M. Leitao, Jubilee Brown, Thomas J.A. Reid, Helen E. Michael, David H. Moore
Journal: Clinical Cancer Research (2015)

In the randomized phase III trial, Gynecologic Oncology Group (GOG) protocol 240, the incorporation of bevacizumab with chemotherapy significantly increased overall survival (OS) in women with advanced cervical cancer. A major objective of GOG-240 was to prospectively analyze previously identified pooled clinical prognostic factors known as the Moore criteria.Potential negative factors included black race, performance status 1, pelvic disease, prior cisplatin, and progression-free interval <365 days. Risk categories included low-risk (0-1 factor), mid-risk (2-3 factors), and high-risk (4-5 factors). Each test of association was conducted at the 5% level of significance. Logistic regression and survival analysis was used to determine whether factors were prognostic or could be used to guide therapy.For the entire population (n = 452), high-risk patients had significantly worse OS (P < 0.0001). The HRs of death for treating with topotecan in low-risk, mid-risk, and high-risk subsets are 1.18 [95% confidence interval (CI), 0.63-2.24], 1.11 (95% CI, 0.82-1.5), and 0.84 (95% CI, 0.50-1.42), respectively. The HRs of death for treating with bevacizumab in low-risk, mid-risk, and high-risk subsets are 0.96 (95% CI, 0.51-1.83; P = 0.9087), 0.673 (95% CI, 0.5-0.91; P = 0.0094), and 0.536 (95% CI, 0.32-0.905; P = 0.0196), respectively.This is the first prospectively validated scoring system in cervical cancer. The Moore criteria have real-world clinical applicability. Toxicity concerns may justify omission of bevacizumab in some low-risk patients where survival benefit is small. The benefit to receiving bevacizumab appears to be greatest in the moderate- and high-risk subgroups (5.8-month increase in median OS). Clin Cancer Res; 21(24); 5480-7. ©2015 AACR.
Aminoguanidine Ameliorates Overexpression of Prosclerotic Growth Factors and Collagen Deposition in Experimental Diabetic Nephropathy
Authors: DARREN J. KELLY, RICHARD E. GILBERT, ALISON J. COX, TINA SOULIS, GEORGE JERUMS, MARK E. COOPER
Journal: Journal of the American Society of Nephrology (2001)

Profibrotic cytokines and the formation of advanced-glycation end products (AGE) have both been implicated in the pathogenesis of glomerulosclerosis in diabetic kidney disease. However, tubulointerstitial pathology is also an important determinant of progressive renal dysfunction in diabetic nephropathy. This study sought to investigate the expression of profibrotic growth factors and matrix deposition in the glomerulus and the tubulointerstitium and to examine the effect of blocking AGE formation in experimental diabetic nephropathy. Thirty-six male Sprague-Dawley rats were randomized into control and diabetic groups. Diabetes was induced in 24 rats by streptozotocin. Twelve diabetic rats were further randomized to receive the inhibitor of AGE formation, aminoguanidine (1 g/l drinking water). At 6 mo, experimental diabetes was associated with a three-fold increase in expression of transforming growth factor (TGF)-β1 (P < 0.01 versus control) and five-fold increase in platelet-derived growth factor (PDGF)-B gene expression (P < 0.01 versus control) in the tubulointerstitium. In situ hybridization demonstrated a diffuse increase in both TGF-β1 and PDGF-B mRNA in renal tubules. Aminoguanidine attenuated not only the overexpression of TGF-β1 and PDGF-B but also reduced type IV collagen deposition in diabetic rats (P < 0.05). TGF-β1 and PDGF mRNA within glomeruli were also similarly increased with diabetes and attenuated with aminoguanidine. The observed beneficial effects of aminoguanidine on the tubulointerstitium in experimental diabetes suggest that AGE-mediated expression of profibrotic cytokines may contribute to tubulointerstitial injury and the pathogenesis of diabetic nephropathy.
<i>IKBKG</i>Mutation With Incontinentia Pigmenti and Ring-Enhancing Encephalopathy
Authors: Deepali Eksambe, Nnenna Agim, Naseem Uddin, Garrett Gotway, Juan M. Pascual
Journal: JAMA Neurology (2015)

This case report describes an infant girl who presented at birth with erythematous vesicles on her hands, progressing to scaly, erythematous plaques on her head, neck, trunk, and extremities in a blaschkoid pattern.
The Emergency Department and the Community: A Model for Improved Cooperation
Authors: J M Hadfield, D W Yates, A Berry
Journal: Journal of the Royal Society of Medicine (1994)

Improved emergency care may be achieved by closer integration of hospital and community management. This has been promoted in Salford by the appointment of an Emergency Services Practice Manager jointly funded by the Family Health Services Authority and Salford Health Authority. Communication has improved, complementary working relationships developed and health promotion initiatives established.
Longitudinal validation of periarticular bone area and 3D shape as biomarkers for knee OA progression? Data from the FNIH OA Biomarkers Consortium
Authors: David Hunter, Michael Nevitt, John Lynch, Virginia Byers Kraus, Jeffrey N Katz, Jamie E Collins, Mike Bowes, Ali Guermazi, Frank W Roemer, Elena Losina
Journal: Annals of the Rheumatic Diseases (2015)

Objective To perform a longitudinal validation study of imaging bone biomarkers of knee osteoarthritis (OA) progression. Methods We undertook a nested case–control study within the Osteoarthritis Initiative in knees (one knee per subject) with a Kellgren and Lawrence grade of 1–3. Cases were defined as knees having the combination of medial tibiofemoral radiographic progression and pain progression at the 24-month, 36-month or 48-month follow-up compared with baseline. Controls (n=406) were eligible knees that did not meet both endpoint criteria and included 200 with neither radiographic nor pain progression, 103 with radiographic progression only and 103 with pain progression only. Bone surfaces in medial and lateral femur, tibia and patella compartments were segmented from MR images using active appearance models. Independent variables of primary interest included change from baseline to 24 months in (1) total area of bone and (2) position on three-dimensional (3D) bone shape vectors that discriminate OA versus non-OA shapes. We assessed the association of bone markers changes over 24 months with progression using logistic regression. Results 24-month changes in bone area and shape in all compartments were greater in cases than controls, with ORs of being a case per 1 SD increase in bone area ranging from 1.28 to 1.71 across compartments, and per 1 SD greater change in 3D shape vectors ranging from 1.22 to 1.64. Bone markers were associated most strongly with radiographic progression and only weakly with pain progression. Conclusions In knees with mild-to-moderate radiographic OA, changes in bone area and shape over 24 months are associated with the combination of radiographic and pain progression over 48 months. This finding of association with longer term clinical outcome underscores their potential for being an efficacy of intervention biomarker in clinical trials.
Trouble in paradise—learning from Hawaii
Authors: Sheila Teasdale
Journal: BMJ (2005)

Roles, responsibilities, and relationships of clinical staff-During the early stages of implementation, changes in clinicians' productivity may require extra staff and the ability to make continuous adjustments.As the organisation adapts to the new electronic system, the capability is needed to document what care a patient received, who provided it and when, so processes may need to adapt to revised professional and legal standards. Limitations of studyOur study captures only a snapshot view, during a volatile phase of implementation and transition from one electronic medical record system to another.The respondents' perceptions should be seen in this context.In fact, another Kaiser Permanente region had implemented an earlier CIS version successfully.However, our overall findings highlight issues likely to be faced by organisations implementing or modifying an electronic medical record system.
PD1-3-5: Evaluation of resected tumors that were not diagnosed histologically but were suspected of lung cancer preoperatively
Authors: Shigeki Sawada, Motohiro Yamashita, Eisaku Komori, Naoyuki Nogami, Isao Oze, Yoshihiko Segawa, Tetsu Shinkai
Journal: Journal of Thoracic Oncology (2007)