tbuckley/cabot-search huggingface dataset:
Efficacy of case method learning in general practice for secondary prevention in patients with coronary artery disease: randomised controlled study
Authors: A. Kiessling
Journal: BMJ (2002)

To study the efficacy of case method learning, for general practitioners, on patients' lipid concentrations in the secondary prevention of coronary artery disease.Prospective controlled trial.Södertälje, Stockholm County, Sweden.255 consecutive patients with coronary artery disease.Guidelines were mailed to all general practitioners (n=54) and presented at a common lecture. General practitioners who were randomised to the intervention group participated in recurrent case method learning dialogues at their primary healthcare centres during a two year period. A locally well known cardiologist served as a facilitator.Concentration of low density lipoprotein cholesterol at baseline and after two years. Analysis according to intention to treat (intervention and control groups (n=88)) was based on group affiliation at baseline.Low density lipoprotein cholesterol was reduced by 0.5 mmol/l (95% confidence interval 0.2 to 0.8 mmol/l) (9.3% (2.9% to 15.8%)) from baseline in patients in the intervention group and by 0.5 (0.1 to 0.9) mmol/l compared with controls (P<0.05). No change occurred in the control group (0.0 (-0.2 to 0.2) mmol/l). Low density lipoprotein cholesterol decreased by 0.6 (0.4 to 0.8) mmol/l in a group of patients who received specialist care.Case method learning resulted in a lowering of low density lipoprotein cholesterol in the primary care patients with coronary artery disease comparable to that achieved at a specialist clinic. Conventional presentation of practice guidelines had no effect.
Clinical utility of total HCV core antigen quantification: A new indirect marker of HCV replication
Authors: Magali Bouvier-Alias, Keyur Patel, Harel Dahari, Stéphanie Beaucourt, Patrick Larderie, Lawrence Blatt, Christophe Hezode, Gaston Picchio, Daniel Dhumeaux, Avidan U. Neumann, John G. McHutchison, Jean-Michel Pawlotsky
Journal: Hepatology (2002)

Hepatitis C virus (HCV) RNA detection, viral load quantification, and HCV genotyping are widely used in clinical practice. Recently, the availability of an anticore antigen (Ag) monoclonal antibody allowed development of an enzyme-linked immunosorbent assay (ELISA) detecting and quantifying total HCV core Ag in peripheral blood of HCV-infected patients. The aims of the present study were to investigate the biologic significance of this new marker in HCV infection, to establish the intrinsic performance of the current assay, and to determine its potential utility in the management of HCV-infected patients. A panel of infected sera calibrated to the World Health Organization International Standard and 657 serum samples from infected patients receiving antiviral treatment were studied. We showed that total HCV core Ag quantification is an accurate, precise, and specific indirect marker of HCV replication. We estimated that 1 pg/mL of total HCV core Ag is equivalent to approximately 8,000 HCV RNA international units (IU)/mL, although minor between-patient differences may exist. In conclusion, total HCV core Ag quantification can be used in the various indications of viral load monitoring, including the evaluation of baseline viral load before therapy, the assessment of the virologic response to antiviral treatment, and the study of early viral kinetics during therapy. Nevertheless, the total HCV core Ag assay cannot be used as a marker of viral replication for HCV RNA values below 20,000 IU/mL, limiting its use in the monitoring of late events during and after antiviral treatment.
Pulmonary hypertension and lung diseases: a suggestion for revision of the clinical classification
Authors: I. Tsangaris, S. Orfanos, D. Bouros
Journal: European Respiratory Journal (2010)

To the Editors: 

We read with great interest the new clinical classification of pulmonary hypertension (PH) 1, that represents a tremendous and successful effort to summarise the existing evidence of a rapidly evolving field in a physician-friendly manner. We want to focus on the inclusion of sarcoidosis, pulmonary Langerhans cells histiocytosis (PCLH) and lymphangioleiomyomatosis (LAM) in the subgroup of PH with unclear or multifactorial aetiologies (Group 5). Although raising such an issue might seem pedantic, we believe that there are …
Annual direct medical cost of active systemic lupus erythematosus in five European countries
Authors: Andrea Doria, Zahir Amoura, Ricard Cervera, Munther A Khamastha, Matthias Schneider, Jutta Richter, Francis Guillemin, Gisela Kobelt, Frédérique Maurel, Anna Garofano, Alessandra Perna, Miranda Murray, Claude Schmitt, Isabelle Boucot
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To evaluate the annual direct medical cost of managing adult systemic lupus erythematosus (SLE) patients with active autoantibody positive disease in Europe. <h3>Methods</h3> A 2-year, retrospective, multicentre, observational study was conducted in five countries (France, Germany, Italy, Spain and the UK). Data included patients' characteristics, disease activity and severity, flare assessments and health resource use (eg, laboratory tests, medications, specialist visits and hospitalisations). Costs were assessed from the public payers' perspective. Cost predictors were estimated by multivariate regression models. <h3>Results</h3> Thirty-one centres enrolled 427 consecutive eligible patients stratified equally by disease severity. At baseline, mean (SD) age was 44.5 (13.8) years, 90.5% were women and mean (SD) SLE duration was 10.7 (8.0) years. The SELENA-SLEDAI (11.2 vs 5.3) and SLICC/ACR index (1.0 vs 0.7) scores were higher in severe patients. Over the study period, patients experienced on average 1.02 (0.71) flares/year. The mean annual direct medical cost was higher in severe compared to non-severe patients (€4748 vs €2650, p&lt;0.001). Medication costs were €2518 in severe versus €1251 in non-severe patients (p&lt;0.001). Medications represented 53% and 47% of the total cost for severe and non-severe patients, respectively, primarily due to immunosuppressants and biologics. Flares, especially severe flares, were identified as the major cost predictor, with each flare increasing the annual total cost by about €1002 (p&lt;0.001). <h3>Conclusions</h3> The annual direct medical cost of SLE patients in Europe is related to disease severity and flares. Medical treatments were the main cost drivers. Severe flares and major organ involvement were identified as important cost predictors.
Pulmonary infections in HIV-infected patients: an update in the 21st century
Authors: N. Benito, A. Moreno, J. M. Miro, A. Torres
Journal: European Respiratory Journal (2011)

From the first descriptions of HIV/AIDS, the lung has been the site most frequently affected by the disease. Most patients develop a pulmonary complication during the history of HIV infection, mainly of infectious aetiology. Important changes in the epidemiology of HIV-related pulmonary infections have occurred. Overall, prescription of <i>Pneumocystis jirovecii</i> prophylaxis and the introduction of highly active antiretroviral therapy (HAART) are the main causes. Currently, the most frequent diagnosis in developed countries is bacterial pneumonia, especially pneumococcal pneumonia, the second most frequent cause is <i>Pneumocystis</i> pneumonia and the third is tuberculosis. However, in Africa, tuberculosis could be the most common pulmonary complication of HIV. Pulmonary infections remain one of the most important causes of morbidity and mortality in these patients, and the first cause of hospital admission in the HAART era. Achieving an aetiological diagnosis of pulmonary infection in these patients is important due to its prognostic consequences.
Successful control of a hospital-wide outbreak of OXA-48 producing Enterobacteriaceae in the Netherlands, 2009 to 2011
Authors: M J Dautzenberg, J M Ossewaarde, M E de Kraker, A van der Zee, S van Burgh, S C de Greeff, H A Bijlmer, H Grundmann, J W Cohen Stuart, A C Fluit, A Troelstra, M Bonten
Journal: Eurosurveillance (2014)

On 31 May 2011, after notification of Klebsiella pneumoniae (KP)(OXA-48;CTX-M-15) in two patients, nosocomial transmission was suspected in a Dutch hospital. Hospital-wide infection control measures and an outbreak investigation were initiated. A total of 72,147 patients were categorised into groups based on risk of OXA-48 colonisation or infection, and 7,527 were screened for Enterobacteriaceae(OXA-48) by polymerase chain reaction (PCR). Stored KP isolates (n=408) were retrospectively tested for OXA-48 and CTX-M-1 group extended-spectrum beta-lactamases (ESBL). 285 KP isolates from retrospective and prospective patient screening were genotyped by amplified fragment length polymorphism (AFLP). 41 isolates harbouring different Enterobacteriaceae species were analysed by plasmid multilocus sequence typing (pMLST). No nosocomial transmission of Enterobacteriaceae(OXA-48) was detected after 18 July 2011. Enterobacteriaceae(OXA-48) were found in 118 patients (KP (n=99), Escherichia coli (n=56), ≥1 Enterobacteriaceae(OXA-48) species (n=52)), of whom 21 had clinical infections. 39/41 (95%) of OXA-48 containing plasmids were identical in pMLST. Minimum inhibitory concentrations (MICs) of KP(OXA-48) and E. coli(OXA-48) for imipenem and meropenem ranged from ≤1 to ≥16 mg/L, and 153/157 (97%) had MIC >0.25 mg/L for ertapenem. AFLP identified a cluster of 203 genetically linked isolates (62 KP(OXA-48;CTX-M15); 107 KP(CTX-M-15); 34 KP(OXA-48)). The ‘oldest’ KP(CTX-M-15) and KP(OXA-48) clonal types originated from February 2009 and September 2010, respectively. The last presumed outbreak-related KP(OXA-48) was detected in April 2012. Uncontrolled transmission of KP(CTX-M-15) evolved into a nosocomial outbreak of KP(OXA-48;CTX-M15) with large phenotypical heterogeneity. Although the outbreak was successfully controlled, the contribution of individual containment measures and of the hospital relocating into a new building just before outbreak notification was impossible to quantify.
Association Between Availability of Health Service Prices and Payments for These Services
Authors: Christopher Whaley, Jennifer Schneider Chafen, Sophie Pinkard, Gabriella Kellerman, Dena Bravata, Robert Kocher, Neeraj Sood
Journal: JAMA (2014)

Recent governmental and private initiatives have sought to reduce health care costs by making health care prices more transparent.To determine whether the use of an employer-sponsored private price transparency platform was associated with lower claims payments for 3 common medical services.Payments for clinical services provided were compared between patients who searched a pricing website before using the service with patients who had not researched prior to receiving this service. Multivariable generalized linear model regressions with propensity score adjustment controlled for demographic, geographic, and procedure differences. To test for selection bias, payments for individuals who used the platform to search for services (searchers) were compared with those who did not use the platform to search for services (nonsearchers) in the period before the platform was available. The exposure was the use of the price transparency platform to search for laboratory tests, advanced imaging services, or clinician office visits before receiving care for that service.Medical claims from 2010-2013 of 502,949 patients who were insured in the United States by 18 employers who provided a price transparency platform to their employees.The primary outcome was total claims payments (the sum of employer and employee spending for each claim) for laboratory tests, advanced imaging services, and clinician office visits.Following access to the platform, 5.9% of 2,988,663 laboratory test claims, 6.9% of 76,768 advanced imaging claims, and 26.8% of 2,653,227 clinician office visit claims were associated with a prior search on the price transparency platform. Before having access to the price transparency platform, searchers had higher claims payments than nonsearchers for laboratory tests (4.11%; 95% CI, 1.87%-6.41%), higher payments for advanced imaging services (5.57%; 95% CI, 1.83%-9.44%), and no difference in payments for clinician office visits (0.26%; 95% CI; 0.53%-0.005%). Following access to the price transparency platform, relative claim payments for searchers were lower for searchers than nonsearchers by 13.93% (95% CI, 10.28%-17.43%) for laboratory tests, 13.15% (95% CI, 9.49%-16.66%) for advanced imaging, and 1.02% (95% CI, 0.57%-1.47%) for clinician office visits. The absolute payment differences were $3.45 (95% CI, $1.78-$5.12) for laboratory tests, $124.74 (95% CI, $83.06-$166.42) for advanced imaging services, and $1.18 (95% CI, $0.66-$1.70) for clinician office visits.Use of price transparency information was associated with lower total claims payments for common medical services. The magnitude of the difference was largest for advanced imaging services and smallest for clinical office visits. Patient access to pricing information before obtaining clinical services may result in lower overall payments made for clinical care.
Cartilage and diarthrodial joints as paradigms for hierarchical materials and structures
Authors: Van C. Mow, Anthony Ratcliffe, A. Robin Poole
Journal: Biomaterials (1992)

The anatomic forms of diarthrodial joints are important structural features which provide and limit the motions required for the joint. Typically, the length scale of topographic variation of anatomic forms ranges from 0.5 to 15 cm. Articular cartilage is the thin layer of hydrated soft tissue (0.5–5.0 mm thick) covering the articulating bony ends in diarthrodial joints. This tissue has a set of unique mechanical and physicochemical properties which are responsible for its load-carrying capabilities and near-frictionless qualities. The mechanical properties of articular cartilage are determined at the tissue-scale level and these properties depend on the composition of the tissue, mainly collagen and proteoglycan, and their molecular and ultrastructural organization (ultra-scale: 10−8–10−6m). Because proteoglycans possess a high density of fixed negative charges, articular cartilage exhibits a significant Donnan osmotic pressure effect. This physicochemically derived osmotic pressure is an important component of the total swelling pressure; the other component of the total swelling pressure stems from the charge-to-charge repulsive force exerted by the closely spaced (1–1.5 nm) negative charge groups along the proteoglycan molecules. Thus these interactions take place at a nano-scale level: 10−10–10−9 m. Finally, cartilage biochemistry and organization are maintained by the chondrocytes which exist at a micro-scale level (10−7–10−6 m). Significant mechanoelectro-chemical transduction occurs within the extracellular matrix at the micro-scale level which affects and modulates cellular anabolic and catabolic activities. At present, the exact details of these transduction mechanisms are unknown. In this review, we present a summary of the hierarchical features for articular cartilage and diarthrodial joints and tables of known material properties for cartilage. Also we summarize how the multi-scale interactions in articular cartilage provide for its unique material properties and tribological characteristics.
A Functional Polymorphism in<i>IL-18</i>Is Associated with Severity of Bronchial Asthma
Authors: Michishige Harada, Kazuhiko Obara, Tomomitsu Hirota, Tomohiro Yoshimoto, Yuki Hitomi, Masafumi Sakashita, Satoru Doi, Akihiko Miyatake, Kimie Fujita, Tadao Enomoto, Masami Taniguchi, Noritaka Higashi, Yuma Fukutomi, Kenji Nakanishi, Yusuke Nakamura, Mayumi Tamari
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

IL-18 is a unique cytokine that enhances innate immunity and both Th1- and Th2-driven immune responses. Recent murine and human genetic studies have shown its role in the pathogenesis of asthma.We conducted an association study in a Japanese population to discover variants of IL-18 that might have an effect on asthma susceptibility and/or progression and conducted functional analyses of the related variants.The IL-18 gene locus was resequenced in 48 human chromosomes. Asthma severity was determined according to the 2002 Global Initiative for Asthma Guidelines. Association and haplotype analyses were performed using 1,172 subjects.Although no polymorphisms differed significantly in frequency between the control and adult asthma groups, rs5744247 C>G was significantly associated with the severity of adult asthma (steps 1, 2 vs. steps 3, 4; P = 0.0034). We also found a positive association with a haplotype (P = 0.0026). By in vitro functional analyses, the rs5744247 variant was found to increase enhancer-reporter activity of the IL-18 gene in bronchial epithelial cells. Expression levels of IL-18 in response to LPS stimulation in monocytes were significantly greater in subjects homozygous for the susceptibility G allele at rs5744247 C>G. Furthermore, we found a significant correlation between the serum IL-18 level and the genotype of rs5744247 (P = 0.031).Although the association results need to be replicated by other studies, IL-18 variants are significantly associated with asthma severity, and the rs5744247 variant reflects higher transcriptional activity and higher expression of IL-18 in LPS-stimulated monocytes and a higher serum IL-18 level.
International Union of Pharmacology. XXII. Nomenclature for Chemokine Receptors
Authors: P M Murphy, M Baggiolini, I F Charo, C A Hébert, R Horuk, K Matsushima, L H Miller, J J Oppenheim, C A Power
Journal: Pharmacological Reviews (2000)

Chemokine receptors comprise a large family of seven transmembrane domain G protein-coupled receptors differentially expressed in diverse cell types. Biological activities have been most clearly defined in leukocytes, where chemokines coordinate development, differentiation, anatomic distribution, trafficking, and effector functions and thereby regulate innate and adaptive immune responses. Pharmacological analysis of chemokine receptors is at an early stage of development. Disease indications have been established in human immunodeficiency virus/acquired immune deficiency syndrome and in Plasmodium vivax malaria, due to exploitation of CCR5 and Duffy, respectively, by the pathogen for cell entry. Additional indications are emerging among inflammatory and immunologically mediated diseases, but selection of targets in this area still remains somewhat speculative. Small molecule antagonists with nanomolar affinity have been reported for 7 of the 18 known chemokine receptors but have not yet been studied in clinical trials. Virally encoded chemokine receptors, as well as chemokine agonists and antagonists, and chemokine scavengers have been identified in medically important poxviruses and herpesviruses, again underscoring the importance of the chemokine system in microbial pathogenesis and possibly identifying specific strategies for modulating chemokine action therapeutically. The purpose of this review is to update current concepts of the biology and pharmacology of the chemokine system, to summarize key information about each chemokine receptor, and to describe a widely accepted receptor nomenclature system, ratified by the International Union of Pharmacology, that is facilitating clear communication in this area.
The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma
Authors: Minghui Li, Aaron R Bolduc, Md Hoda, Denise N Gamble, Sarah-Bianca Dolisca, Anna K Bolduc, Kelly Hoang, Claire Ashley, David McCall, Amyn M Rojiani, Bernard L Maria, Olivier Rixe, Tobey J MacDonald, Peter S Heeger, Andrew L Mellor, David H Munn, Theodore S Johnson
Journal: Journal for ImmunoTherapy of Cancer (2014)

Indoleamine 2,3-dioxygenase (IDO) is an enzyme with immune-suppressive properties that is commonly exploited by tumors to evade immune destruction. Anti-tumor T cell responses can be initiated in solid tumors, but are immediately suppressed by compensatory upregulation of immunological checkpoints, including IDO. In addition to these known effects on the adaptive immune system, we previously showed widespread, T cell-dependent complement deposition during allogeneic fetal rejection upon maternal treatment with IDO-blockade. We hypothesized that IDO protects glioblastoma from the full effects of chemo-radiation therapy by preventing vascular activation and complement-dependent tumor destruction.To test this hypothesis, we utilized a syngeneic orthotopic glioblastoma model in which GL261 glioblastoma tumor cells were stereotactically implanted into the right frontal lobes of syngeneic mice. These mice were treated with IDO-blocking drugs in combination with chemotherapy and radiation therapy.Pharmacologic inhibition of IDO synergized with chemo-radiation therapy to prolong survival in mice bearing intracranial glioblastoma tumors. We now show that pharmacologic or genetic inhibition of IDO allowed chemo-radiation to trigger widespread complement deposition at sites of tumor growth. Chemotherapy treatment alone resulted in collections of perivascular leukocytes within tumors, but no complement deposition. Adding IDO-blockade led to upregulation of VCAM-1 on vascular endothelium within the tumor microenvironment, and further adding radiation in the presence of IDO-blockade led to widespread deposition of complement. Mice genetically deficient in complement component C3 lost all of the synergistic effects of IDO-blockade on chemo-radiation-induced survival.Together these findings identify a novel mechanistic link between IDO and complement, and implicate complement as a major downstream effector mechanism for the beneficial effect of IDO-blockade after chemo-radiation therapy. We speculate that this represents a fundamental pathway by which the tumor regulates intratumoral vascular activation and protects itself from immune-mediated tumor destruction.
The TIM-1
Authors: Song Rong, Joon-Keun Park, Torsten Kirsch, Hideo Yagita, Hisaya Akiba, Olaf Boenisch, Hermann Haller, Nader Najafian, Antje Habicht
Journal: Journal of the American Society of Nephrology (2011)

CD4+ T cells contribute to the pathogenesis of ischemia-reperfusion injury, which is the primary cause of delayed graft failure after kidney transplantation. The TIM-1:TIM-4 pathway participates in the activation/differentiation of CD4+ T cells, suggesting that it may modulate ischemia-reperfusion injury. Here, we studied the role of TIM-1 in a murine uninephrectomized renal ischemia-reperfusion injury model. Blocking the TIM-1:TIM-4 pathway with an antagonistic monoclonal antibody protected renal function and diminished reperfusion injury resulting from 30 minutes of ischemia. Histologic examination showed significantly less evidence of renal damage as evidenced by diminished tubular necrosis, preservation of the brush border, fewer cast formations, and less tubular dilation. Blocking TIM-1 also reduced the number of apoptotic cells and diminished local inflammation within ischemic kidneys, the latter shown by decreased recruitment of macrophages, neutrophils, and CD4+ T cells and by reduced local production of proinflammatory cytokines. Furthermore, TIM-1 blockade significantly improved survival after ischemia-reperfusion injury. Taken together, these data suggest that the TIM-1:TIM-4 pathway enhances injury after renal ischemia-reperfusion injury and may be a therapeutic target.
Transcatheter Aortic-Valve Endocarditis Confirmed by Transesophageal Echocardiography
Authors: Mathias Orban, Daniel Sinnecker, Helmut Mair, Michael Nabauer, Christian Kupatt, Christoph Schmitz, Steffen Massberg, Karl-Ludwig Laugwitz, Petra Barthel
Journal: Circulation (2013)