tbuckley/cabot-search huggingface dataset:
Cost effectiveness of brace, physiotherapy, or both for treatment of tennis elbow
Authors: P A A Struijs, I B C Korthals-de Bos, M W van Tulder, C N van Dijk, L M Bouter, W J J Assendelft
Journal: British Journal of Sports Medicine (2006)

Background: The annual incidence of tennis elbow in the general population is high (1–3%). Tennis elbow often leads to limitation of activities of daily living and work absenteeism. Physiotherapy and braces are the most common treatments. Objectives: The hypothesis of the trial was that no difference exists in the cost effectiveness of physiotherapy, braces, and a combination of the two for treatment of tennis elbow. Methods: The trial was designed as a randomised controlled trial with intention to treat analysis. A total of 180 patients with tennis elbow were randomised to brace only (n = 68), physiotherapy (n = 56), or a combination of the two (n = 56). Outcome measures were success rate, severity of complaints, pain, functional disability, and quality of life. Follow up was at six, 26, and 52 weeks. Direct healthcare and non-healthcare costs and indirect costs were measured. Mean cost differences over 12 months were evaluated by applying non-parametric bootstrap techniques. Results: No clinically relevant or statistically significant differences were found between the groups. Success rate at 12 months was 89% in the physiotherapy group, 86% in the brace group, and 87% in the combination group. Mean total costs per patient were €2069 in the brace only group, €978 in the physiotherapy group, and €1256 in the combination group. The mean difference in total costs between the physiotherapy and brace group was substantial (€1005), although not significant. Cost effectiveness ratios and cost utility ratios showed physiotherapy to be the most cost effective, although this also was not statistically significant. Conclusion: No clinically relevant or statistically significant differences in costs were identified between the three strategies.
Synergistic Antitumor Activity of Ixabepilone (BMS-247550) Plus Bevacizumab in Multiple <i>In vivo</i> Tumor Models
Authors: Francis Y.F. Lee, Kelly L. Covello, Stephen Castaneda, Donald R. Hawken, David Kan, Anne Lewin, Mei-Li Wen, Rolf-Peter Ryseck, Craig R. Fairchild, Joseph Fargnoli, Robert Kramer
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Angiogenesis is a critical step in the establishment, growth, and metastasis of solid tumors, and combination of antiangiogenic agents with chemotherapy is an attractive therapeutic option. We investigated the potential of ixabepilone, the first in a new class of antineoplastic agents known as epothilones, to synergize with antiangiogenic agents to inhibit tumor growth. Experimental Design: In vitro and in vivo cytotoxicity of ixabepilone as single agent and in combination with two targeted antiangiogenic agents, bevacizumab or sunitinib, were examined in preclinical tumor models. Direct effects of the agents against endothelial cells was also examined and compared with the effects of paclitaxel as single agent and in combination with bevacizumab. Results: Ixabepilone showed robust synergistic antitumor activity in combination with bevacizumab and sunitinib in preclinical in vivo models derived from breast, colon, lung, and kidney cancers. The synergistic antitumor effect was greater with ixabepilone compared with paclitaxel. Furthermore, ixabepilone was more effective than paclitaxel at killing endothelial cells expressing P-glycoprotein in vitro and inhibiting endothelial cell proliferation and tumor angiogenesis in vivo. Conclusions: Ixabepilone may enhance the antitumor effects of antiangiogenic therapy by direct cytotoxicity and also indirectly via the killing of tumor-associated endothelial cells. Given that ixabepilone has reduced susceptibility to drug efflux pumps compared with taxanes, these data may explain the increased antiangiogenic and antitumor activity of ixabepilone in combination with antiangiogenic agents. Phase II studies to assess the efficacy and safety of ixabepilone plus bevacizumab in locally recurrent or metastatic breast cancer are planned.
An amnesty for unpublished trials (Reprinted from the <i>BMJ</i> 1997;<b>315</b>: 622)
Authors: Richard Smith, Ian Roberts
Journal: Gut (1997)

This month over 100 medical journals around the world are inviting readers to send information on unpublished trials. This amnesty should have important benefits for patients. Why?

Reports of properly conducted randomised controlled trials are the foundation of effective health care, but many are not submitted for publication.1 2 This reduces the power of systematic reviews to detect moderate but clinically important treatment effects. Patients may thus be denied effective forms of health care. A second problem is that since trials that show more promising effects are more likely to be submitted, research syntheses can give misleading conclusions about effectiveness. Patients may thus …
Downregulation of T cell responses by antibodies to the T cell receptor.
Authors: S Webb, J Sprent
Journal: The Journal of Experimental Medicine (1987)

We have derived a T cell clone that recognizes and responds to three different types of antigen: self + X (fowl gamma globulin + H-2d), allo-H-2p,b, and minor lymphocyte-stimulating (Mlsa,d) determinants. Anti-TcR mAb and their F(ab')2 and Fab fragments were tested for their capacity to block the response of this clone. When responses were assayed on day 4 or later, addition of KJ16 or F23.1 mAb caused a marked inhibition of the response to each of the three antigens recognized by the clone. Responses measured at earlier time points however were unaffected or enhanced. This finding suggested that the inhibitory effects of anti-TcR mAb that followed the phase of enhancement might have reflected downregulation of the cells rather than simple blockade of TcR. In support of this possibility it was found that addition of anti-TcR mAb caused marked inhibition of the response of the clone to IL-2, i.e., a response that is not known to involve the TcR.
Long-Term Breast-Feeding in Women With Type 1 Diabetes
Authors: Edna Stage, Hanne Nørgård, Peter Damm, Elisabeth Mathiesen
Journal: Diabetes Care (2006)

Breast-feeding may be more difficult in women with diabetes because of neonatal morbidity and fluctuating maternal blood glucose values. The frequency of long-term breast-feeding and the possible predictors for successful breast-feeding were investigated.One hundred two consecutive women with type 1 diabetes were interviewed about breast-feeding using a semistructured questionnaire 5 days and 4 months after delivery. Clinical data were collected from the medical records.Five days after delivery, 86% of the women were breast-feeding. Four months after delivery, 55 (54%) women were exclusively, 14 (14%) were partly, and 33 (32%) were not breast-feeding compared with 50, 26, and 24% in the background population (NS). Mothers exclusively breast-feeding at 4 months were characterized by previous experience with breast-feeding, a higher educational level, and vaginal delivery and included a high proportion of nonsmokers, whereas there were no associations with diabetes-related parameters such as white classes, duration of diabetes, HbA(1c), and insulin dose at conception. Breast-fed offspring had a significantly higher birth weight and gestational age and were less often receiving glucose intravenously compared with the remaining offspring. Independent predictors of exclusive breast-feeding at 4 months were previous experience with breast-feeding (odds ratio 6.3 [95% CI 2.4-17]) and higher educational level (7.1 [2.4-21]). Cessation of breast-feeding was mainly due to common nursing problems, such as perceived milk supply, and not related to maternal diabetes status.The majority of the women with type 1 diabetes initiated breast-feeding, and the prevalence of breast-feeding at 4 months was comparable to that in the background population. Independent predictors of exclusive breast-feeding at 4 months were previous experience with breast-feeding and higher educational level.
Shortening of the Elastic Tandem Immunoglobulin Segment of Titin Leads to Diastolic Dysfunction
Authors: Charles S. Chung, Kirk R. Hutchinson, Mei Methawasin, Chandra Saripalli, John E. Smith, Carlos G. Hidalgo, Xiuju Luo, Siegfried Labeit, Caiying Guo, Henk L. Granzier
Journal: Circulation (2013)

Background— Diastolic dysfunction is a poorly understood but clinically pervasive syndrome that is characterized by increased diastolic stiffness. Titin is the main determinant of cellular passive stiffness. However, the physiological role that the tandem immunoglobulin (Ig) segment of titin plays in stiffness generation and whether shortening this segment is sufficient to cause diastolic dysfunction need to be established. Methods and Results— We generated a mouse model in which 9 Ig-like domains (Ig3–Ig11) were deleted from the proximal tandem Ig segment of the spring region of titin (IG KO). Exon microarray analysis revealed no adaptations in titin splicing, whereas novel phospho-specific antibodies did not detect changes in titin phosphorylation. Passive myocyte stiffness was increased in the IG KO, and immunoelectron microscopy revealed increased extension of the remaining titin spring segments as the sole likely underlying mechanism. Diastolic stiffness was increased at the tissue and organ levels, with no consistent changes in extracellular matrix composition or extracellular matrix–based passive stiffness, supporting a titin-based mechanism for in vivo diastolic dysfunction. Additionally, IG KO mice have a reduced exercise tolerance, a phenotype often associated with diastolic dysfunction. Conclusions— Increased titin-based passive stiffness is sufficient to cause diastolic dysfunction with exercise intolerance.
Pirmenol, a new antiarrhythmic agent: initial study of efficacy, safety and pharmacokinetics.
Authors: S C Hammill, D G Shand, P A Routledge, M C Hindman, J T Baker, E L Pritchett
Journal: Circulation (1982)

Pirmenol (CI-845), a new antiarrhythmic drug, was studied for the first time in humans to establish a minimum effective i.v. dose in 10 patients with chronic, stable premature ventricular complexes (PVCs) and to evaluate toxicity and pharmacokinetics. Infusions of 70-150 mg were associated with a 90% or greater reduction in PVCs nine of the 12 times they were administered to six patients. Peak plasma concentrations were 1.0-3.8 micrograms/ml at the end of these infusions. At the same time, small but significant increases in diastolic blood pressure (4 mm Hg) and QTc interval (0.01 second) were seen, but both values were within the normal range. Pirmenol was associated with no change in heart rate, systolic blood pressure, PR interval or QRS duration, renal, hepatic or hematologic function, or symptoms. Blood, plasma and free drug concentrations declined biexponentially after cessation of a 150-mg infusion (n = 4), with a terminal half-life of 7-9.4 hours. The therapeutic response, lack of toxicity, and relatively long half-life indicate that pirmenol is a promising antiarrhythmic agent.
TIPS with a polytetrafluoroethylene-lined stent graft and associated haemolytic anaemia.
Authors: E Fallon, E Ehrenwald, G K Nazarian, C I Smith
Journal: Gut (2008)

We read with interest the recent paper by Salerno et al ( Gut 2007; 56 :1310–8) describing transjugular intrahepatic portosystemic shunts (TIPS) as improving renal function and ascites in cirrhosis. We report a case of haemolytic anaemia following TIPS with a Viatorr (GORE, Flagstaff, AZ, USA) ePTFE-lined stent. Post-TIPS haemolytic anaemia was reported with the use of bare metal stents in the 1990s.1–3 In recent years stents lined with expanded polytetrafluoroethylene (ePTFE) have been used in TIPS and are thought to have a decreased rate of complications.4

A 63-year-old woman with autoimmune hepatitis that had progressed to cirrhosis was requiring weekly paracentesis due to refractory ascites. Because of her low Model for End Stage Liver Disease (MELD) score she was referred for a TIPS to …
The Need for Multiple Measures of Hospital Quality
Authors: Adrian F. Hernandez, Gregg C. Fonarow, Li Liang, Paul A. Heidenreich, Clyde Yancy, Eric D. Peterson
Journal: Circulation (2011)

Process and outcome measures are often used to quantify quality of care in hospitals. Whether these quality measures correlate with one another and the degree to which hospital provider rankings shift on the basis of the performance metric is uncertain.Heart failure patients ≥ 65 years of age hospitalized in the Get With the Guidelines-Heart Failure registry of the American Heart Association were linked to Medicare claims from 2005 to 2006. Hospitals were ranked by (1) composite adherence scores for 5 heart failure process measures, (2) composite adherence scores for emerging quality measures, (3) risk-adjusted 30-day death after admission, and (4) risk-adjusted 30-day readmission after discharge. Hierarchical models using shrinkage estimates were performed to adjust for case mix and hospital volume. There were 19 483 patients hospitalized from 2005 to 2006 from 153 hospitals. The overall median composite adherence rate to heart process measures was 85.8% (25th, 75th percentiles 77.5, 91.4). Median 30-day risk-adjusted mortality was 9.0% (7.9, 10.4). Median risk-adjusted 30-day readmission was 22.9% (22.1, 23.5). The weighted κ for remaining within the top 20th percentile or bottom 20th percentile was ≤ 0.15 and the Spearman correlation overall was ≤ 0.21 between the different measures of quality of care. The average shift in ranks was 33 positions (13, 68) when criteria were changed from 30-day mortality to readmission and 51 positions (22, 76) when ranking metric changed from 30-day mortality to composite process adherence.Agreement between different methods of ranking hospital-based quality of care and 30-day mortality or readmission rankings was poor. Profiling quality of care will require multidimensional ranking methods and/or additional measures.
Functional expression of B7/BB1 on activated T lymphocytes.
Authors: M Azuma, H Yssel, J H Phillips, H Spits, L L Lanier
Journal: The Journal of Experimental Medicine (1993)

B7/BB1 is a membrane differentiation antigen expressed on activated B cells, macrophages, and dendritic cells that binds to a counter-receptor, CD28, expressed on T lymphocytes and thymocytes. Interaction between CD28 and B7 results in potent costimulation of T cell activation initiated via the CD3/T cell receptor complex. We now report that B7 is also expressed on activated human peripheral blood T cells, CD4 T cell clones, CD8 T cell clones, and natural killer cell clones. B7 appears relatively late after T cell activation, can be detected on both CD4 and CD8 T cell subsets, and is present on antigen-specific, major histocompatibility complex-restricted CD4 and CD8 T cell clones. Expression of B7 on activated T cells was confirmed by immunoprecipitation from 125I-labeled activated T cells and by detection of B7 transcripts. A B7+ CD4+ T cell clone was able to stimulate a primary allogeneic mixed lymphocyte response using small, resting peripheral blood T cells as responders. The alloantigen-induced proliferative response and cytokine production was partially inhibited by anti-B7 monoclonal antibody. Since activated T cells can coexpress both CD28 and its counter-receptor, B7, this suggests that activated T cells may be capable of autocrine costimulation via the CD28 activation pathway.
Collaborative Care Management of Late-Life Depression in the Primary Care Setting
Authors: Jürgen Unützer, Wayne Katon, Christopher M. Callahan, John W. Williams, Jr, Enid Hunkeler, Linda Harpole, Marc Hoffing, Richard D. Della Penna, Polly Hitchcock Noël, Elizabeth H. B. Lin, Patricia A. Areán, Mark T. Hegel, Lingqi Tang, Thomas R. Belin, Sabine Oishi, Christopher Langston, None for the IMPACT Investigators
Journal: JAMA (2002)

ContextFew depressed older adults receive effective treatment in primary care settings.ObjectiveTo determine the effectiveness of the Improving Mood–Promoting Access to Collaborative Treatment (IMPACT) collaborative care management program for late-life depression.DesignRandomized controlled trial with recruitment from July 1999 to August 2001.SettingEighteen primary care clinics from 8 health care organizations in 5 states.ParticipantsA total of 1801 patients aged 60 years or older with major depression (17%), dysthymic disorder (30%), or both (53%).InterventionPatients were randomly assigned to the IMPACT intervention (n = 906) or to usual care (n = 895). Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care expert and who offered education, care management, and support of antidepressant management by the patient's primary care physician or a brief psychotherapy for depresssion, Problem Solving Treatment in Primary Care.Main Outcome MeasuresAssessments at baseline and at 3, 6, and 12 months for depression, depression treatments, satisfaction with care, functional impairment, and quality of life.ResultsAt 12 months, 45% of intervention patients had a 50% or greater reduction in depressive symptoms from baseline compared with 19% of usual care participants (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.71-4.38; P&lt;.001). Intervention patients also experienced greater rates of depression treatment (OR, 2.98; 95% CI, 2.34-3.79; P&lt;.001), more satisfaction with depression care (OR, 3.38; 95% CI, 2.66-4.30; P&lt;.001), lower depression severity (range, 0-4; between-group difference, −0.4; 95% CI, −0.46 to −0.33; P&lt;.001), less functional impairment (range, 0-10; between-group difference, −0.91; 95% CI, −1.19 to −0.64; P&lt;.001), and greater quality of life (range, 0-10; between-group difference, 0.56; 95% CI, 0.32-0.79; P&lt;.001) than participants assigned to the usual care group.ConclusionThe IMPACT collaborative care model appears to be feasible and significantly more effective than usual care for depression in a wide range of primary care practices.
Atypical ?s haplotypes are generated by diverse genetic mechanisms
Authors: M.A. Zago, W.A. Silva, B. Dalle, S. Gualandro, M.H. Hutz, C. Lapoumeroulie, M.H. Tavella, A.G. Araujo, J.E. Krieger, J. Elion, R. Krishnamoorthy
Journal: American Journal of Hematology (2000)

The majority of the chromosomes with the βS gene have one of the five common haplotypes, designated as Benin, Bantu, Senegal, Cameroon, and Arab-Indian haplotypes. However, in every large series of sickle cell patients, 5–10% of the chromosomes have less common haplotypes, usually referred to as "atypical" haplotypes. In order to explore the genetic mechanisms that could generate these atypical haplotypes, we extended our analysis to other rarely studied polymorphic markers of the βS-gene cluster, in a total of 40 chromosomes with uncommon haplotypes from Brazil and Cameroon. The following polymorphisms were examined: seven restriction site polymorphisms of the ϵγδβ-cluster, the pre-Gγ framework sequence including the 6-bp deletion/insertion pattern, HS-2 LCR (AT)xR(AT)y and pre-β (AT)xTy repeat motifs, the GC/TT polymorphism at −1105–1106 of Gγ-globin gene, the C/T polymorphism at −551 of the β-globin gene, and the intragenic β-globin gene framework. Among the Brazilian subjects, the most common atypical structure (7/16) was a Bantu 3′-subhaplotype associated with different 5′-sequences, while in two chromosomes a Benin 3′-subhaplotype was associated with two different 5′-subhaplotypes. A hybrid Benin/Bantu configuration was also observed. In three chromosomes, the atypical haplotype differed from the typical one by the change of a single restriction site. In 2/134 chromosomes identified as having a typical Bantu RFLP-haplotype, a discrepant LCR repeat sequence was observed, probably owing to a crossover 5′ to the ϵ-gene. Among 80 βS chromosomes from Cameroon, 22 were associated with an atypical haplotype. The most common structure was represented by a Benin haplotype (from the LCR to the β-gene) with a non-Benin segment 3′ to the β-globin gene. In two cases a Bantu LCR was associated with a Benin haplotype and a non-Benin segment 3′ to the β-globin gene. In three other cases, a more complex structure was observed that can be considered as a hybrid of Benin, Bantu, Senegal, or other chromosomes was observed. These data suggest that the atypical βS haplotypes are not uncommon in America and in Africa. These haplotypes are probably generated by a variety of genetic mechanisms including (a) isolated nucleotide changes in one of the polymorphic restriction sites, (b) simple and double crossovers between two typical βS haplotypes or much more frequently between a typical βS haplotype and a different βA-associated haplotype that was present in the population, and (c) gene conversions. Am. J. Hematol. 63:79–84, 2000. © 2000 Wiley-Liss, Inc.
Quality control of synovial fluid crystal identification
Authors: R. von Essen, A. M H Holtta, R. Pikkarainen
Journal: Annals of the Rheumatic Diseases (1998)

To establish a quality assessment programme for the diagnosis of crystal arthropathies by synovial fluid (SF) microscopy.Three or four cytocentrifuge slides prepared from suitable patient SF specimens were distributed to 25-47 predominantly Finnish clinical laboratories once a year. Sodium urate crystals were included in every survey.Returns for the years 1989-1996 were reviewed. Laboratories that participated in > four surveys made on an average one error a year (range 0.25-2). The error rate for specimens containing abundant crystals was acceptable but it increased considerably for specimens showing few crystals per microscope field. No laboratory characteristic predictive of successful performance was found.Errors in quality assessment results for crystal identification were much more frequent than in the fields of, for example, clinical chemistry or microbiology. Despite efforts to provide educational feedback, no improvement was seen during the study period. Because of the dearth of data from other parts of the world it is not known for certain whether this study has merely pinpointed a local problem or if the same trend applies elsewhere.
Neurological Events During Long-Term Mechanical Circulatory Support for Heart Failure
Authors: Ronald M. Lazar, Peter A. Shapiro, Brian E. Jaski, Michael K. Parides, Robert C. Bourge, John T. Watson, Laura Damme, Walter Dembitsky, Jeffrey D. Hosenpud, Lopa Gupta, Anita Tierney, Tonya Kraus, Yoshifumi Naka
Journal: Circulation (2004)

Progression of heart failure can lead to cardiac transplantation, but when patients are ineligible, long-term mechanical circulatory support may improve survival. The REMATCH trial showed that left ventricular assist devices (LVADs) prolonged survival in patients with end-stage disease, but with a significant number of adverse events. We report on the neurological outcomes in the REMATCH trial.We examined new neurological events in the 129 patients randomized to either LVAD placement (n=68) or medical management (n=61), classified as stroke, transient ischemic attack, toxic-metabolic encephalopathy, and other. There were 46 neurological events: 42 in 30 LVAD patients and 4 in 4 patients in the medical arm (chi2, 30/68 versus 4/61, P<0.001). Sixteen percent of the LVAD patients had a stroke, with a rate of 0.19 per year (95% CI, 0.10 to 0.33), many occurring in the postoperative period. The stroke rate in the medical arm was 0.052. A Kaplan-Meier survival analysis showed a 44% reduction in the risk of stroke or death in the LVAD group versus the optimal medical group (P=0.002). The mean interval from implantation to stroke was 221.8 days (+/-70.4 days). History of stroke, age, and sepsis were not stroke risk factors in the LVAD group.Fewer than half of the patients in the LVAD group had a neurological event, and there were few neurological deaths. Survival analysis combining stroke or death demonstrated a significant benefit for long-term circulatory support with an LVAD over medical therapy. Future trials will need to address prospectively all neurological outcomes, including neurocognitive function, and the role of long-term neuroprotection.