tbuckley/cabot-search huggingface dataset:
Association of Funding and Conclusions in Randomized Drug Trials
Authors: Bodil Als-Nielsen, Wendong Chen, Christian Gluud, Lise L. Kjaergard
Journal: JAMA (2003)

Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions.To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events.Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication).Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not.The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events.Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data.
O7.05 * DIFFERENTIATION OF LOCAL RECURRENT BRAIN METASTASIS FROM RADIATION-INDUCED CHANGES USING O-(2-[18F]FLUOROETHYL)-L-TYROSINE PET
Authors: N. Galldiks, M. I. Ruge, C. Hamisch, G. Stoffels, G. Ceccon, M. Rapp, M. Sabel, K. Langen
Journal: Neuro-Oncology (2014)

BACKGROUND: The aim of this study was to investigate the potential of O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET for differentiating local recurrent brain metastasis from radiation-induced changes after radiation therapy since the use of contrast-enhanced MRI for this issue is often difficult. METHODS: 38 patients (mean age, 54 ± 11 y) with single or multiple contrast-enhancing brain lesions (n = 49) on MRI after radiation therapy of brain metastases were investigated with dynamic 18F-FET PET. Maximum and mean tumor/brain ratios (20-40 min postinjection) (TBRmax, TBRmean) of 18F-FET uptake were determined. Time activity curves (TAC) were generated and the time-to-peak (TTP) was calculated. Furthermore, TACs of each lesion were assigned to one of the following curve patterns: (I) constantly increasing 18F-FET uptake; (II) 18F-FET uptake peaking early (TTP ≤ 20 min) followed by a plateau; and (III) 18F-FET uptake peaking early (TTP ≤ 20 min) followed by a constant descent. The diagnostic accuracy of the TBRmax and TBRmean of 18F-FET uptake and the curve patterns for the correct identification of recurrent brain metastasis was evaluated by receiver-operating-characteristic (ROC) analyses using subsequent histological analysis (17 lesions in 16 patients) or clinical course and MR imaging findings (32 lesions in 22 patients) as reference. RESULTS: Both TBRmax and TBRmean were significantly higher in patients with recurrent metastasis (n = 25) than in patients with radiation-induced changes (n = 24) (TBRmax 3.3 ± 1.0 vs. 2.3 ± 0.4, P < 0.001; TBRmean 2.2 ± 0.4 vs. 1.7 ± 0.1, P < 0.001). The sensitivity/specificity of 18F-FET PET for the correct identification of recurrent brain metastases was 84 / 79% using TBRmax (area under the curve, 0.851 ± 0.06, cut-off 2.6; P < 0.001), 92/83% using TBRmean (area under the curve, 0.901 ± 0.05, cut-off 1.9; P < 0.001), and 84/100% for curve patterns II and III vs. curve pattern I (P < 0.001). Highest sensitivity/specificity (96/88%) to diagnose local recurrent metastasis was obtained when both a TBRmean ≥1.9 and curve pattern II or III were present (area under the curve, 0.963 ± 0.03; P < 0.001). CONCLUSION: Our findings suggest that the combined evaluation of the TBRmean of 18F-FET uptake and the pattern of TAC can differentiate local brain metastasis recurrence from radiation-induced changes with high accuracy. 18F-FET PET may thus contribute significantly to the management of patients with brain metastases.
A comparative study of periarticular bone lesions in rheumatoid arthritis and psoriatic arthritis
Authors: S. Finzel, M. Englbrecht, K. Engelke, C. Stach, G. Schett
Journal: Annals of the Rheumatic Diseases (2010)

Psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are both destructive arthritides but may differ substantially in their periarticular bone changes.To investigate the differences in the structural changes of periarticular bone in patients with PsA and RA by a high-resolution imaging technique designed to visualise the bone architecture.30 patients with PsA and 58 patients with RA received a µCT scan to compare structural bone changes in the metacarpophalangeal joints of the dominantly affected hand. Number, extent, form and distribution of bone erosions, osteophytes and cortical thinning were recorded. In addition, the size and depth of bone erosions and the size of osteophytes were determined.Patients with PsA and RA had the same number of bone erosions, but they were less severe and overall smaller in size and depth in PsA. Erosions in PsA were mostly Ω-shaped and tubule-shaped, whereas U-shaped lesions were most typical for RA. Erosions in PsA were more evenly distributed, lacking the strong preponderance for the radial sites found in RA. Osteophytes were increased in number, extent and size in PsA as compared with RA, often affecting the entire circumference of bone ('bony corona').High-resolution µCT imaging shows profound differences in periarticular bone changes between PsA and RA. Smaller Ω-shaped and tubule-shaped bone erosions as well as large sometimes corona-shaped osteophytes are typical for PsA. These data suggest that mechanisms of bone repair may be more active in PsA than in RA.
Asthma in preschool children: prevalence and risk factors
Authors: M M Haby
Journal: Thorax (2001)

Background-The prevalence of asthma in children has increased in many countries over recent years.To plan eVective interventions to reverse this trend we need a better understanding of the risk factors for asthma in early life.This study was undertaken to measure the prevalence of, and risk factors for, asthma in preschool children.Methods-Parents of children aged 3-5 years living in two cities (Lismore, n=383; Wagga Wagga, n=591) in New South Wales, Australia were surveyed by questionnaire to ascertain the presence of asthma and various proposed risk factors for asthma in their children.Recent asthma was defined as ever having been diagnosed with asthma and having cough or wheeze in the last 12 months and having used an asthma medication in the last 12 months.Atopy was measured by skin prick tests to six common allergens.Results-The prevalence of recent asthma was 22% in Lismore and 18% in Wagga Wagga.Factors which increased the risk of recent asthma were: atopy (odds ratio (OR) 2.35, 95% CI 1.49 to 3.72), having a parent with a history of asthma (OR 2.05, 95% CI 1.34 to 3.16), having had a serious respiratory infection in the first 2 years of life (OR 1.93, 95% CI 1.25 to 2.99), and a high dietary intake of polyunsaturated fats (OR 2.03, 95% CI 1.15 to 3.60).Breast feeding (OR 0.41, 95% CI 0.22 to 0.74) and having three or more older siblings (OR 0.16, 95% CI 0.04 to 0.71) decreased the risk of recent asthma.Conclusions-Of the factors tested, those that have the greatest potential to be modified to reduce the risk of asthma are breast feeding and consumption of polyunsaturated fats.
Inappropriate line use within the in-patient parenteral nutrition population: frequency &amp; usage
Authors: N. E. Burch, J. Stewart, N. Smith
Journal: Gut (2011)

<h3>Introduction</h3> In June 2010, the National Confidential Enquiry into Patient Outcome and Death published ‘A Mixed Bag: an enquiry into the care of in-patients receiving parenteral nutrition’ (PN). This study found only 19% of inpatients received care with respect to their PN that was considered good. It also revealed widespread variability in the type of venous access secured for the purpose of PN administration, with only 42% of lines being inserted solely for the use of PN. This further analysis aimed to delineate the frequency of line use for purposes other than PN, and the nature of this additional usage. <h3>Methods</h3> All patients in England and Wales who received PN between 1st January and 31st March 2008 were identified from pharmacy records. Two patients per consultant were identified. A clinical questionnaire was sent to be completed by the consultant for each patient, and then returned with a copy of the case notes. The questionnaires and case notes were then analysed by our Advisor group consisting of consultants, dieticians and pharmacists. <h3>Results</h3> Clinicians reported utilising a centrally inserted venous catheter (CVC) in 73% of patients (762/1042) for initial PN administration, with 15% (153/1042) via peripherally inserted central venous catheter (PICC), and 12% (127/1042) via peripheral cannula. Of those inserted, 73% were multilumen, and 27% single lumen lines. Lines were used for purposes other than PN in 37% (224/605). The most frequent usage of the CVC in addition to PN was for iv drugs and fluids combined (50%). Additional documented uses included: fluids alone (31%), drugs alone (13%), and other (6%). In 26% of cases there was a CVC related complication as deemed by the advisors. The commonest CVC complication was either suspected (36%) or confirmed line infection (23%). Overall rate of proven CVC related sepsis was 6% (45/734), and suspected line infection 9.5% (70/734), excluding patients where there was insufficient data. <h3>Conclusion</h3> These results demonstrate a significant proportion of CVC use for purposes other than PN. Overall incidence of CVC-related sepsis in the literature varies widely from 1.3% to 26.2% of patients receiving PN.1 Use of a multilumen CVC is associated with the highest frequency of CVC-related sepsis.2 This is likely to reflect the high incidence of concurrent drug and fluid administration via a multilumen line as shown in this analysis. These results emphasise the importance of the ASPEN and BAPEN guidelines recommending single lumen CVCs for PN administration, a dedicated lumen in multilumen lines, and the avoidance of CVC use other than for PN where possible.
Increased expression of IL-16 in inflammatory bowel disease
Authors: D Seegert, P Rosenstiel, H Pfahler, P Pfefferkorn, S Nikolaus, S Schreiber
Journal: Gut (2001)

Inflammatory bowel disease (IBD) is characterised by infiltration of inflamed mucosal regions with CD4(+) T lymphocytes and other mononuclear cells. Interleukin (IL)-16 exerts a strong chemoattractant activity on CD4(+) cells. Moreover, IL-16 activates expression and production of proinflammatory cytokines such as IL-1beta, IL-6, IL-15, and tumour necrosis factor alpha (TNF-alpha) in human monocytes.To examine if IL-16 expression is increased in IBD patients compared with healthy controls.Twenty one patients with IBD (10 with ulcerative colitis (UC), 11 with Crohn's disease (CD)), seven disease specificity controls (DSC), and seven healthy controls were studied. Biopsies were taken during colonoscopies and IL-16 mRNA as well as protein expression were investigated by reverse transcriptase-polymerase chain reaction, ELISA, western blot, and immunohistochemistry.IL-16 mRNA and protein expression in the colonic mucosa of IBD patients were increased twofold compared with healthy controls, DSC, or IBD patients under steroid treatment. Most of the detected IL-16 protein was in its bioactive 17 kDa form and was predominantly expressed in eosinophils. Increased IL-16 expression in UC patients appeared to be mainly restricted to the inflamed regions of the colonic mucosa. Levels of caspase 3, which processes the 68 kDa IL-16 precursor molecule into the biological active 17 kDa form, were not increased.Our results provide evidence that IL-16 expression is significantly increased in the inflamed colonic mucosa of IBD patients but not in control individuals, DSC, or patients under steroid treatment. Therefore, upregulation of IL-16 expression seems to be specific for chronic intestinal inflammation and could lead to increased secretion of other proinflammatory cytokines in IBD.
EFFECTIVENESS OF CARDIAC SCREENING INCLUSIVE OF ECG IN YOUNG ATHLETES:
Authors: B Toresdahl, H Pelto, J Fudge, K Harmon, A Rao, I Asif, D Owens, J Prutkin, J Salerno, J Drezner
Journal: British Journal of Sports Medicine (2014)

Background The primary objective of pre-participation screening in athletes is the detection of potentially lethal cardiac conditions. The American Heart Association (AHA) recommends a directed history and physical examination. The added value of electrocardiogram (ECG) screening is debated. % of Abnormalities Detected False Positive Rate Positive Predictive Value History 47.8% 22.3% 1.0% Physical 30.4% 14.9% 1.0% ECG 69.6% 3.6% 8.6% Objective To determine the effectiveness of different cardiac screening strategies in young competitive athletes. Setting Heart screening events in U.S. high schools from October 2010 through June 2013. Patients Competitive athletes ages 13-19. Interventions Heart health questionnaire and physical examination based on AHA recommendations, resting 12-lead ECG, and echocardiogram if indicated. Main outcome measurements Prevalence of potentially lethal cardiac conditions, false-positive results, and positive predictive value for testing procedures. Results 4,812 athletes underwent cardiac screening (54% male, 46% female; 65% Caucasian, 10% Asian, 6% African-American, and 19% other). 23 athletes (0.5%, 1 in 209) were identified with a potentially lethal cardiac condition including 9 Wolff-Parkinson-White, 4 coronary artery anomaly, 3 dilated aortic root/aneurysm, 3 long QT syndrome, 2 hypertrophic cardiomyopathy, 1 ventricular arrhythmia, and 1 short QT syndrome. Abnormal history or physical findings led to the diagnosis in 14/23 (61%) disorders and an abnormal ECG led to the diagnosis in 16/23 (70%). The addition of ECG led to detection of 7/23 (30%) athletes not otherwise identified by the AHA protocol. One case was identified by echocardiography without a relevant abnormality on history, physical, or ECG. Conclusions Standardized history and physical examination has a high false-positive rate in cardiac screening of young athletes. ECG screening using modern interpretation criteria provides a low false-positive rate and increases the likelihood of detecting disorders associated with sudden cardiac death. An integrated screening protocol using history, physical examination, and ECG is recommended for pre-participation screening in young athletes.
Transforming growth factor beta 1: in situ expression in the liver of patients with chronic hepatitis C treated with alpha interferon.
Authors: P Bedossa, T Poynard, P Mathurin, G Lemaigre, J C Chaput
Journal: Gut (1993)

In a semiquantitative assessment of the expression of transforming growth factor (TGF) beta 1 in liver biopsy specimens from patients with chronic hepatitis C, treatment with interferon alfa-2b (3 million units (MU) three times weekly) decreased the expression of TGF beta 1 in six of seven patients. The reduction in TGF beta 1 correlated significantly with the scores for inflammation (p &lt; 0.05) and necrosis (p &lt; 0.05), but not with the alanine aminotransferase activities (p = 0.36) or the score for fibrosis (p = 0.86).
Randomized Phase III Trial of Topotecan Following Carboplatin and Paclitaxel in First-line Treatment of Advanced Ovarian Cancer: A Gynecologic Cancer Intergroup Trial of the AGO-OVAR and GINECO
Authors: Jacobus Pfisterer, Béatrice Weber, Alexander Reuss, Rainer Kimmig, Andreas du Bois, Uwe Wagner, Hugues Bourgeois, Werner Meier, Serban Costa, Jens-Uwe Blohmer, Alain Lortholary, Sigrid Olbricht, Anne Stähle, Christian Jackisch, Anne-Claire Hardy-Bessard, Volker Möbus, Jens Quaas, Barbara Richter, Willibald Schröder, Jean-François Geay, Hans-Joachim Lück, Walther Kuhn, Harald Meden, Ulrike Nitz, Eric Pujade-Lauraine
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: The combination of carboplatin and paclitaxel is the standard of care for the treatment of ovarian cancer, yet rates of recurrence and death remain high. We performed a prospective randomized phase III study to examine whether sequential administration of topotecan can improve the efficacy of carboplatin and paclitaxel in first-line treatment of advanced epithelial ovarian cancer. Methods: A total of 1308 patients with previously untreated ovarian cancer (International Federation of Gynecology and Obstetrics stages IIB–IV) were randomly assigned to receive six cycles of paclitaxel and carboplatin followed by either four cycles of topotecan (TC-Top; 658 patients) or surveillance (TC; 650 patients) on a 3-week per cycle schedule. The primary endpoint was overall survival, and secondary endpoints were progression-free survival, response rate, toxicity, and quality of life. Time-to-event data were analyzed using the Kaplan–Meier method, and a stratified log-rank test was used to compare distributions between treatment groups. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model. Categorical data were compared using a stratified Cochran–Mantel–Haenszel test. All statistical tests were two-sided. Results: Median progression-free survival was 18.2 months in the TC-Top arm versus 18.5 months in the TC arm (stratum-adjusted HR = 0.97 [95% CI = 0.85 to 1.10]; P = .688). Median overall survival was 43.1 months for the TC-Top arm versus 44.5 months for the TC arm (stratum-adjusted HR = 1.01 [95% CI = 0.86 to 1.18]; P = .885). At 3 years, overall survival in both arms was 57% (58.5% in the TC arm and 55.7% in the TC-Top arm). Compared with patients in the TC arm, patients in the TC-Top arm had more grade 3–4 hematologic toxic effects (requiring more supportive care) and more grade 3–4 infections (5.1% versus 2.7%; P = .034) but did not have a statistically significant increase in febrile neutropenia (3.3% versus 3.1%; P = .80). Among patients who had measurable disease (TC, n = 147; TC-Top, n = 145), overall (i.e., complete or partial) response was 69.0% (95% CI = 61.4% to 76.5%) in the TC-Top arm and 76.2% (95% CI = 69.3% to 83.1%) in the TC arm ( P = .166). Conclusions: The sequential addition of topotecan to carboplatin–paclitaxel did not result in superior overall response or progression-free or overall survival. Therefore, this regimen is not recommended as standard of care treatment for ovarian cancer.
An annotated cDNA library and microarray for large-scale gene-expression studies in the ant Solenopsis invicta.
Authors: John Wang, Stephanie Jemielity, Paolo Uva, Yannick Wurm, Johannes Gräff, Laurent Keller
Journal: Genome biology (2007)

Ants display a range of fascinating behaviors, a remarkable level of intra-species phenotypic plasticity and many other interesting characteristics. Here we present a new tool to study the molecular mechanisms underlying these traits: a tentatively annotated expressed sequence tag (EST) resource for the fire ant Solenopsis invicta. From a normalized cDNA library we obtained 21,715 ESTs, which represent 11,864 putatively different transcripts with very diverse molecular functions. All ESTs were used to construct a cDNA microarray.
Words, grammar, and number concepts: Evidence from development and aphasia
Authors: Rosemary Varley, Michael Siegal
Journal: Behavioral and Brain Sciences (2001)

Bloom's book underscores the importance of specifying the role of words and grammar in cognition. We propose that the cognitive power of language lies in the lexicon rather than grammar. We suggest ways in which studies involving children and patients with aphasia can provide insights into the basis of abstract cognition in the domain of number and mathematics.
Clinical pilot study of a cytotoxic antiserum in myeloblastic leukemia
Authors: M. F. Heyworth, J. S. Wainscoat, A. M. O'Hea, J. A. Schifferli
Journal: American Journal of Hematology (1982)

Abstract A large dose of equine antilymphocytic globulin (ALG, 120 mg/kg/day) was given intravenously to four patients with myeloblastic leukemia. Leukemic myeloblasts from each patient were lysed by the ALG in vitro, in the presence of the same patient's serum complement. In each patient, ALG infusion was followed by a reduction in the count of circulating leukemic myeloblasts, and a fall in the serum levels of C3 and C4 complement. It is likely that complement‐mediated lysis of circulating leukemic myeloblasts occurred in these patients, as a result of ALG administration.