tbuckley/cabot-search huggingface dataset:
P284 Quality Improvements and Cost Savings Associated with the Integration of COPD Care in Coventry
Authors: CM Gelder, M Horn, J Horn, G Washington
Journal: Thorax (2012)

<h3>Introduction</h3> Coventry had high admissions rates for COPD, and poor co-ordination between primary and secondary care. There was generally low interest in COPD and poor attendance at educational meetings. An audit revealed that 74% of individuals with COPD admitted to hospital made contact with their practise in the month before admissions and 58% had received 3 or more courses of antibiotics in the year prior to admission, indicating the potential to improve care quality and reduce costs. <h3>Methods</h3> We reviewed current provision against NICE standards and the emerging National COPD Strategy, identified gaps and agreed priorities. In parallel a patient and carer consultation was undertaken using focus groups, interviews and questionnaires. This information was used to formulate a model that integrated primary and secondary care and shared clinical pathways. Key was the establishment of a consultant led community based COPD team. To allow individual practises to benchmark themselves against NICE standards and then support them to develop their own improvement plans, a COPD management tool (POINTS) was introduced into most practises. Financial incentives (QP 8 and QP 11) were used to drive key elements, in particular improved recording of exacerbations, the use of rescue packs and self-management plans. Education for Primary Care Nurses was made “user-friendly” and delivered as monthly ‘bite size’ education sessions, with GP reimbursement for nurse time. <h3>Results</h3> There has been a high level of support and engagement from primary and secondary care. COPD is now the top local LTC priority. During the first year admissions and re-admissions have reduced by approximately 15%. More than 90% of COPD outpatient activity is now in the community (including post discharge follow up). Patient surveys have shown very high levels of satisfaction. The project has been cost neutral in its first year (including savings from Oxygen Register cleansing but excluding savings from moving outpatient care to the community team) and the CCGs project savings of approximately £300,000 and £600,000 at 24 and 36 months. <h3>Discussion</h3> This demonstrates that service redesign can deliver rapid improvements in the quality of care with significant cost savings potential.
Innovation in high-performance sports medicine
Authors: C A Speed, W O Roberts
Journal: British Journal of Sports Medicine (2010)

High-performance sports medicine (HPSM) is an area of sport and exercise medicine (SEM) that deals with distinct groups of individuals who can differ from the general population in many ways, including their physiology, psychology and behaviour. As detailed in the first article of this series, provision of medical care to the high-performance athlete can involve specific and often unconventional models of working to facilitate the delivery of optimum medical care to the athlete and team. This is still an evolving area, and the best models of care will vary between sports, athletes and nations. However, the evidence base relating to best-practice medical care in the elite athlete population is currently lacking. Unproven and at times inappropriate approaches are common in HPSM, and athletes must be protected from these. While research issues form the subject of the following article, here we discuss the great opportunity—and a necessity—for innovation to help to provide best practice. Innovation is not easy: it requires huge commitment and proactive creativity to explore novel methods and models that suit specific sports. Carefully selected models and methods can then be thoroughly scrutinised through rigorous research. This article focuses upon the nature and process of innovation, and its importance to the development of HPSM. Importantly, many of the examples given also have relevance in the field of SEM in general.

Innovation is the act of introducing something new. In high-performance sport, the description ‘change that creates a new dimension of performance’1 may help to focus the concept. ‘Performance’ may apply either to the athlete's performance or to the delivery of care. Innovation is critical to the advancement of all walks of life and has a strong foundation in business model literature, but is now recognised as a critical aspect in the development of healthcare systems and processes.2 …
Further Observations on the Inhibition of Tumor Growth by &lt;italic&gt;Corynebacterium parvum&lt;/italic&gt; With Cyclophosphamide. IX. Macrophage Content of Tumors in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M C Gebhardt, B Fisher
Journal: JNCI Journal of the National Cancer Institute (1979)

Repeated observations with the use of a murine system indicated that tumor growth inhibition resulting from the administration of cyclophosphamide (CY) and Corynebacterium parvum was greater than that occurring after the administration of either agent alone. Investigations were directed toward the determination of whether this effect could be related to an increase in the proportion of macrophages in tumors of treated C3HeB/FeJ female mice. Two different methods for tumor macrophage detection, the Fc receptor analysis and the quantitation of phagocytic mononuclear cells, were employed; the results were compared with two separate controls. No evidence was obtained to indicate that tumor inhibition by any of the treatments employed was associated with an increase in the macrophage content of tumors. Neither local nor systemic administration of C. parvum with or without CY, which resulted in tumor growth inhibition, led to an increase in tumor macrophages. CY given systemically was associated with a rise in the proportion of phagocytic cells, but this rise occurred in tumors lealt affected by such therapy. The content of macrophages in untreated tumors remained constant until tumors reached large sizes, at which time the percentage of Fc receptor-bearing cells decreased. These findings did not imply that the macrophage was uninvolved in the antitumor effect of CY and C. parvum; however, they did suggest that it is unlikely that the effect of local or systemic C. parvum administered with or without CY is mediated by an increase in the number of macrophages within tumors.
Novel Effects of Neutrophil-Derived Proteinase 3 and Elastase on the Vascular Endothelium Involve In Vivo Cleavage of NF-κB and Proapoptotic Changes in JNK, ERK, and p38 MAPK Signaling Pathways
Authors: Gloria A. Preston, Christopher S. Zarella, William F. Pendergraft, Earl H. Rudolph, Jia Jin Yang, Stephen B. Sekura, J. Charles Jennette, Ronald J. Falk
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Leukocyte-derived proteases have long been considered simply degradative. However, emerging data raise possibilities of a complex and specific biologic role for these proteases in substrate processing and in signaling pathways within cells. This study reports that the release of neutrophilic and monocytic proteases, such as proteinase 3 (PR3) and human neutrophil elastase (HNE), can result in their entry into endothelial cells coincident with the activation of proapoptotic-signaling events through ERK, JNK, and p38 MAPK. Inhibition of JNK blocked PR3-induced apoptosis, and inhibition of p38 MAPK blocked PR3- and HNE-induced apoptosis, indicating that these pathways are required for activation of apoptosis. It is here shown that protease entry results in direct cleavage of p65 NF-κB in the N-terminal region by PR3 and in the C-terminal region by HNE. This cleavage results in diminished transcriptional activity by NF-κB as demonstrated by diminished levels of TNF-α–induced IL-8 message in the presence of PR3 or HNE. Inhibition of caspases did not block the cleavage of p65 NF-κB, and sequence analysis showed that the PR3 and HNE cleavage sites are unique with respect to reported caspase sites. The data demonstrate that PR3 and HNE have specific, fundamental roles in endothelial responses during inflammation. Upon entry, they can usurp the cell's control of its own fate by directly intervening into caspase cascades. This provides a unique mechanism of crosstalk between leukocytes and endothelial cells at sites of inflammation that impacts both cytokine networks and cell viability.
Predicting outcomes in radiation oncology—multifactorial decision support systems
Authors: Philippe Lambin, Ruud G. P. M. van Stiphout, Maud H. W. Starmans, Emmanuel Rios-Velazquez, Georgi Nalbantov, Hugo J. W. L. Aerts, Erik Roelofs, Wouter van Elmpt, Paul C. Boutros, Pierluigi Granone, Vincenzo Valentini, Adrian C. Begg, Dirk De Ruysscher, Andre Dekker
Journal: Nature Reviews Clinical Oncology (2012)
The L1 Cell Adhesion Molecule Is Induced in Renal Cancer Cells and Correlates with Metastasis in Clear Cell Carcinomas
Authors: Yves Allory, Yasuko Matsuoka, Céline Bazille, Erik Ilsø Christensen, Pierre Ronco, Hanna Debiec
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The L1 cell adhesion molecule is overexpressed in many human carcinomas. The objectives of the study were to provide a comprehensive description of L1 distribution in human kidney and to establish the prognostic relevance of L1 expression in renal cell carcinomas (RCC). Experimental Design: Using two antibodies to the extracellular part and the cytoplasmic domain, respectively, we first compared L1 expression in normal kidney and renal tumors of diverse histopathologic origin, then we studied L1 expression together with tumor stage, grade, molecular prognostic biomarkers, and metastatic behavior. Results: In normal kidney, L1 immunoreactive with both antibodies was expressed in all epithelial cells originating from the ureteric bud except for intercalated cells. In renal tumors, L1 was mainly detected in those originating from cells that do not express L1 in the normal kidney [i.e., 33 of 72 clear cell RCC (ccRCC) and 25 of 88 papillary RCC (papRCC)]. Both in ccRCC and papRCC, L1 reacted only with the antibody to the extracellular domain, suggesting that the protein was truncated. In these carcinomas, L1 expression was strongly correlated with Ki-67 proliferation index (ccRCC, P = 0.0059; papRCC, P = 0.0039), but only in ccRCC, the presence of L1 was associated with the risk of metastasis (P = 0.0121). This risk was higher if cyclin D1 was concurrently absent in tumor cells (P &amp;lt; 0.0001). The L1+/cyclin D1− profile was an independent prognostic factor of metastasis occurrence in multivariate analysis (P = 0.0023). Conclusion: We have found a combination of markers that can serve to identify a subgroup of high-risk patients with ccRCC that may require more aggressive therapies.
Behavioral Therapies for Drug Abuse
Authors: Kathleen M. Carroll, Lisa S. Onken
Journal: American Journal of Psychiatry (2005)

The past three decades have been marked by tremendous progress in behavioral therapies for drug abuse and dependence, as well as advances in the conceptualization of approaches to development of behavioral therapies. Cognitive behavior therapy, contingency management, couples and family therapy, and a variety of other types of behavioral treatment have been shown to be potent interventions for several forms of drug addiction, and scientific progress has also been greatly facilitated by the articulation of a systematic approach to the development, evaluation, and dissemination of behavioral therapies. The authors review recent progress in strategies for the development of behavioral therapies for drug and alcohol abuse and dependence and discuss the range of effective behavioral therapies that are currently available.
Low levels of heme oxygenase-1 in induced sputum of lung cancer patients as a marker of defective cytoprotection
Authors: Amir Bar-Shai, Alon Ahimor, Moshe Stark, Elizabeth Fireman
Journal: European Respiratory Journal (2012)

Background : Lung cancer is a leading cause of morbidity and mortality worldwide, resulting in substantial economic and social burdens that are constantly increasing.

There is a strong correlation between inflammation and oxidative stress and malignant transformation. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that plays a central role in the defense against oxidative stress. HO-1 has anti-inflammatory, anti-proliferative and anti-apoptotic properties and is involved in the regulation of immunological balance in a wide range of lung diseases, including lung cancer.

Aims : To investigate the role of HO-1 as an anti-oxidant and anti-inflammatory enzyme in the pathogenesis of lung cancer, by comparing its activity in induced sputum (IS) of patients with lung cancer, patients with COPD and healthy nonsmokers controls.

Methods: IS was conducted according to a standard protocol. HO-1 levels were measured in IS supernatant by a biliverdin reductase-dependant reaction using bilirubin as end product.

Results: 90 subjects (31 with lung cancer, 29 with COPD and 30 healthy nonsmokers) underwent IS and HO-1 level measurements. Mean HO-1 levels were significantly (p<0.0001) lower in lung cancer patients compares to COPD patients and healthy controls, (0.645, 1.192 and 1.628 respectively). There was a negative correlation between the lung cancer stage and HO-1 activity.

Conclusions: HO-1 activity is reduced in patients with lung cancer and correlates with disease severity, suggesting its protective effect as an antioxidant enzyme. These findings may propose a role of agents stimulating HO-1 as a novel therapeutic approach in lung cancer.
Alternative Activation of Macrophages: An Immunologic Functional Perspective
Authors: Fernando O. Martinez, Laura Helming, Siamon Gordon
Journal: Annual Review of Immunology (2008)

Macrophages are innate immune cells with well-established roles in the primary response to pathogens, but also in tissue homeostasis, coordination of the adaptive immune response, inflammation, resolution, and repair. These cells recognize danger signals through receptors capable of inducing specialized activation programs. The classically known macrophage activation is induced by IFN-gamma, which triggers a harsh proinflammatory response that is required to kill intracellular pathogens. Macrophages also undergo alternative activation by IL-4 and IL-13, which trigger a different phenotype that is important for the immune response to parasites. Here we review the cellular sources of these cytokines, receptor signaling pathways, and induced markers and gene signatures. We draw attention to discrepancies found between mouse and human models of alternative activation. The evidence for in vivo alternative activation of macrophages is also analyzed, with nematode infection as prototypic disease. Finally, we revisit the concept of macrophage activation in the context of the immune response.
Role of interleukin 10 in murine postoperative ileus
Authors: B Stoffels, J Schmidt, A Nakao, A Nazir, R S Chanthaphavong, A J Bauer
Journal: Gut (2009)

Intestinal manipulation triggers an inflammatory cascade within the muscularis causing postoperative ileus (POI). The aim of this study was to investigate the recovery and therapeutic potential of interleukin 10 (IL10) for POI.POI was induced by bowel surgical manipulation (SM) in wild-type, IL10(-/-) and recombinant murine IL10 (rmIL10)-treated mice. Immunohistochemistry localised IL10 in the muscularis externa, histochemistry quantified neutrophil recruitment, and quantitative PCR quantified alterations in mRNA. Luminex multiplex analysis, Griess reaction and ELISA measured proteins, nitric oxide (NO) and prostanoid release from the muscularis externa, respectively, in 24 h organ culture. Gastrointestinal transit and jejunal circular muscle organ bath techniques assessed gastrointestinal function.In IL10 knockouts compared with the wild type, the expression of numerous proinflammatory mRNAs (IL6, IL1 beta, chemokine C-C motif ligand 2 (CCL2) and haem oxygenase-1) and proteins (IL6, IL1 alpha, IL12, IL17, interferon gamma, tumour necrosis factor alpha, CCL2, interferon-inducible protein-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) were accentuated, and release of muscle inhibitors NO and prostanoids was increased; motility never recovered from manipulation and mortality rate was 87.5%. In wild types, complete functional recovery occurred in 7 days with no mortality. SM delay in transit and suppression in jejunal circular muscle contractions were significantly improved by rmIL10 treatment. Upregulation in IL1 beta, IL6 and CCL2 mRNAs and inflammatory mediators (IL1 alpha, IL6, CCL2, macrophage inflammatory protein-1 alpha, GM-CSF, NO and prostaglandin) after SM were significantly less with rmIL10 treatment, which resulted in a decrease in neutrophil recruitment compared with SM controls.IL10 plays an obligatory role in postoperative intestinal recovery, and exogenous IL10 prevents its development. Pre-emptive exogenous recombinant human IL10 could be a treatment for the prevention of clinical POI.
Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial
Authors: John C Araujo, Géralyn C Trudel, Fred Saad, Andrew J Armstrong, Evan Y Yu, Joaquim Bellmunt, George Wilding, John McCaffrey, Sergio V Serrano, Vsevolod B Matveev, Eleni Efstathiou, Stephane Oudard, Michael J Morris, Bruce Sizer, Peter J Goebell, Axel Heidenreich, Johann S de Bono, Stephen Begbie, Jun H Hong, Eduardo Richardet, Enrique Gallardo, Prashni Paliwal, Susan Durham, Shinta Cheng, Christopher J Logothetis
Journal: The Lancet Oncology (2013)
Tricyclic antidepressants and headaches: systematic review and meta-analysis
Authors: J. L. Jackson, W. Shimeall, L. Sessums, K. J. DeZee, D. Becher, M. Diemer, E. Berbano, P. G. O'Malley
Journal: BMJ (2010)

To evaluate the efficacy and relative adverse effects of tricyclic antidepressants in the treatment of migraine, tension-type, and mixed headaches.Meta-analysis.Medline, Embase, the Cochrane Trials Registry, and PsycLIT. Studies reviewed Randomised trials of adults receiving tricyclics as only treatment for a minimum of four weeks.Frequency of headaches (number of headache attacks for migraine and number of days with headache for tension-type headaches), intensity of headache, and headache index.37 studies met the inclusion criteria. Tricyclics significantly reduced the number of days with tension-type headache and number of headache attacks from migraine than placebo (average standardised mean difference -1.29, 95% confidence interval -2.18 to -0.39 and -0.70, -0.93 to -0.48) but not compared with selective serotonin reuptake inhibitors (-0.80, -2.63 to 0.02 and -0.20, -0.60 to 0.19). The effect of tricyclics increased with longer duration of treatment (β=-0.11, 95% confidence interval -0.63 to -0.15; P<0.0005). Tricyclics were also more likely to reduce the intensity of headaches by at least 50% than either placebo (tension-type: relative risk 1.41, 95% confidence interval 1.02 to 1.89; migraine: 1.80, 1.24 to 2.62) or selective serotonin reuptake inhibitors (1.73, 1.34 to 2.22 and 1.72, 1.15 to 2.55). Tricyclics were more likely to cause adverse effects than placebo (1.53, 95% confidence interval 1.11 to 2.12) and selective serotonin reuptake inhibitors (2.22, 1.52 to 3.32), including dry mouth (P<0.0005 for both), drowsiness (P<0.0005 for both), and weight gain (P<0.001 for both), but did not increase dropout rates (placebo: 1.22, 0.83 to 1.80, selective serotonin reuptake inhibitors: 1.16, 0.81 to 2.97).Tricyclic antidepressants are effective in preventing migraine and tension-type headaches and are more effective than selective serotonin reuptake inhibitors, although with greater adverse effects. The effectiveness of tricyclics seems to increase over time.
Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group
Authors: Richard B. Womer, Daniel C. West, Mark D. Krailo, Paul S. Dickman, Bruce R. Pawel, Holcombe E. Grier, Karen Marcus, Scott Sailer, John H. Healey, John P. Dormans, Aaron R. Weiss
Journal: Journal of Clinical Oncology (2012)

Chemotherapy with alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide cycles and primary tumor treatment with surgery and/or radiation therapy constitute the usual approach to localized Ewing sarcoma in North America. We tested whether chemotherapy intensification through interval compression could improve outcome.This was a prospective, randomized controlled trial for patients younger than 50 years old with newly diagnosed localized extradural Ewing sarcoma. Patients assigned to standard and intensified treatment were to begin chemotherapy cycles every 21 and 14 days, respectively, provided an absolute neutrophil count greater than 750×10(6)/L and a platelet count greater than 75×10(9)/L. Patients received vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1.2 g/m2) alternating with ifosfamide (9 g/m2) and etoposide (500 mg/m2) for 14 cycles, with filgrastim (5 mg/kg per day; maximum, 300 mg) between cycles. Primary tumor treatment (surgery, radiation, or both) was to begin at week 13 (after four cycles in the standard arm and six cycles in the intensified arm). The primary end point was event-free survival (EFS). The study is registered at ClinicalTrials.gov (identifier: NCT00006734).Five hundred eighty-seven patients were enrolled and randomly assigned, and 568 patients were eligible, with 284 patients in each regimen. For all cycles, the median cycle interval for standard treatment was 21 days (mean, 22.45 days); for intensified treatment, the median interval was 15 days (mean, 17.29 days). EFS at a median of 5 years was 65% in the standard arm and 73% in the intensified arm (P=.048). The toxicity of the regimens was similar.For localized Ewing sarcoma, chemotherapy administered every 2 weeks is more effective than chemotherapy administered every 3 weeks, with no increase in toxicity.
End Points for Colon Cancer Adjuvant Trials: Observations and Recommendations Based on Individual Patient Data From 20,898 Patients Enrolled Onto 18 Randomized Trials From the ACCENT Group
Authors: Daniel J. Sargent, Smitha Patiyil, Greg Yothers, Daniel G. Haller, Richard Gray, Jacqueline Benedetti, Marc Buyse, Roberto Labianca, Jean Francois Seitz, Christopher J. O'Callaghan, Guido Francini, Axel Grothey, Michael O'Connell, Paul J. Catalano, David Kerr, Erin Green, Harry S. Wieand, Richard M. Goldberg, Aimery de Gramont
Journal: Journal of Clinical Oncology (2007)

The traditional end point for colon adjuvant clinical trials is overall survival (OS). We previously validated disease-free survival (DFS) after 3-year follow-up as an excellent predictor of 5-year OS results. Here we explore shorter term DFS and OS end points, as well as stage dependency.Individual patient data from 18 phase III trials including 43 arms and 20,898 patients were pooled. Association measures included correlation of event rates within arms, correlation of hazard ratios (HRs) between arms, trial level significance comparisons (via log-rank testing), and a formal surrogacy model.DFS at earlier times was less accurate in predicting OS than 3-year DFS, but 2-year DFS remained a strong predictor. DFS with 1-year minimum follow-up demonstrated perfect negative predicted value; all trials negative at 1 year for DFS were negative for 5-year OS. OS with 3-year minimum follow-up was also an excellent predictor for 5-year OS; OS at earlier time points provided inaccurate prediction. The association between 3-year DFS and 5-year OS was greater for stage III patients; correlation of HR within trials was 0.92 (95% CI, 0.85 to 0.95) for stage III patients and 0.70 (95% CI, 0.44 to 0.80) for stage II patients.DFS outcomes after 2- or 3-year median follow-up are excellent predictors of 5-year OS. DFS outcomes are appropriate for trials in which the majority of patients are stage III. DFS after 2- or 3-year median follow-up should be considered as the primary end point in future colon adjuvant trials.