tbuckley/cabot-search huggingface dataset:
Population Pharmacokinetics of Enoxaparin During the Antenatal Period
Authors: Jignesh P. Patel, Bruce Green, Raj K. Patel, Michael S. Marsh, J. Graham Davies, Roopen Arya
Journal: Circulation (2013)

Background— The optimal dosing strategy of low-molecular-weight heparins for the treatment of antenatal venous thromboembolism is not known. The physiological changes associated with pregnancy alter the pharmacokinetic profile of low-molecular-weight heparins, which has led to controversy and subsequent variation in practice, when pregnant women with venous thromboembolism are treated with low-molecular-weight heparins. Our objective was to develop a robust pharmacokinetic model of enoxaparin during the antenatal period to address this problem. Method and Results— Women prescribed antenatal enoxaparin were eligible to enroll in the study. Recruited women were reviewed monthly and had up to 3 anti-Xa activities (trough and 1 and 3 hours after dose) drawn at each clinic attendance. Compartmental pharmacokinetic modeling was conducted using nonlinear mixed-effects modeling. One hundred twenty-three patients contributed 795 anti-Xa activities for pharmacokinetic modeling purposes. Both enoxaparin clearance and volume of distribution were increased during pregnancy. Simulations of once- versus twice-daily enoxaparin administration demonstrated that both dosing regimens would reach target 3-hour plasma concentrations throughout the duration of the pregnancy. When trough anti-Xa activity was simulated, both once- and twice-daily regimens exhibited an increase in trough anti-Xa activity with the progression of pregnancy. This is explained by the significant increase in volume of distribution observed during pregnancy. Conclusions— The half-life of enoxaparin is prolonged with the progression of pregnancy, and our work provides compelling evidence for prescribing once-daily enoxaparin for the treatment of antenatal venous thromboembolism. National and international guideline recommendations should be reconsidered.
Respiratory symptoms, asthma, exercise test spirometry, and atopy in schoolchildren from a Lima shanty town
Authors: M E Penny, S Murad, S S Madrid, T S Herrera, A Piñeiro, D E Caceres, C F Lanata
Journal: Thorax (2001)

Little is known about the associations between symptoms of asthma, pulmonary function tests, and atopy in developing countries. While asthma in children is often associated with atopy, some studies of wheezing illness have found little or no association, leading to suggestions that there are subgroups of wheezing illness. The ISAAC study recently reported that the prevalence of reported asthma symptoms in Lima, Peru was among the highest in the world, but did not report on the atopic status of the subjects.A cross sectional survey was conducted of children aged 8-10 years who had previously participated in a cohort study of respiratory and diarrhoeal illnesses in infancy. Questionnaires were administered asking about respiratory symptoms and asthma diagnoses, pulmonary function tests were performed before and after exercise on a treadmill, and atopy was determined from skin prick tests and specific serum IgE levels.A total of 793 children participated in the survey. The prevalence of asthma related symptoms in the last 12 months was 23.2%, but only 3.8% of children reported a recent asthma attack. The mean differences in pretest percentage predicted forced expiratory volume in one second (FEV(1)) were 8.1% (95% CI 2.4 to 13.8) between children who did and did not report an asthma attack in the last 12 months, and 5.3% (95% CI 2.8 to 7.9) in children who did and did not report respiratory symptoms. The corresponding differences in mean percentage fall in FEV(1) after exercise were 3.1% (95% CI -1 to 7.1) and 5.1% (95% CI 3.4 to 6.8). Recent asthma or respiratory symptoms were not associated with atopy in this population (odds ratios 1.29 (95% CI 0.56 to 2.97) and 0.91 (95% CI 0.61 to 1.37), respectively).Most asthma in these children was unrecognised and mild. Asthma and asthma symptoms in this population do not seem to be related to atopy.
Clarithromycin reduces the severity of bronchial hyperresponsiveness in patients with asthma
Authors: E. Kostadima, S. Tsiodras, E.I. Alexopoulos, A.G. Kaditis, I. Mavrou, N. Georgatou, A. Papamichalopoulos
Journal: European Respiratory Journal (2004)

A randomised double-blind placebo-controlled study was designed to evaluate the effects of a semisynthetic macrolide antibiotic, clarithromycin, on bronchial hyperresponsiveness to methacholine in patients with a diagnosis of asthma. Adult asthma patients undergoing treatment with budesonide 400 microg b.i.d. and salbutamol 200 microg p.r.n. less than twice weekly were studied. Arm A (16 males/six females, aged 48 +/- 16 yrs) received clarithromycin 250 mg b.i.d. for 8 weeks, arm B (eight males/12 females, aged 42 +/- 12 yrs) clarithromycin 250 mg t.id. and arm C (six males/15 females, aged 41 +/- 16 yrs) placebo dextrose tablets. Bronchial hyperresponsiveness was quantified by measurement of the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20). Median (interquartile range) PD20 in the three groups before and after treatment with clarithromycin were: arm A: 0.3 (0.1-1) and 1.3 (0.6-2) mg; arm B: 0.4 (0.1-0.9) and 2 (2-2) mg; and arm C: 0.4 (0.1-0.9) and 0.3 (0.1-0.6) mg, respectively. Serum free cortisol levels were determined and remained unchanged from baseline in the clarithromycin-treated patients. It is concluded that clarithromycin reduces the degree of bronchial hyperresponsiveness in patients with asthma.
The outcome and cost-effectiveness of nurse-led care in people with rheumatoid arthritis: a multicentre randomised controlled trial
Authors: Mwidimi Ndosi, Martyn Lewis, Claire Hale, Helen Quinn, Sarah Ryan, Paul Emery, Howard Bird, Jackie Hill
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To determine the clinical effectiveness and cost-effectiveness of nurse-led care (NLC) for people with rheumatoid arthritis (RA). <h3>Methods</h3> In a multicentre pragmatic randomised controlled trial, the assessment of clinical effects followed a non-inferiority design, while patient satisfaction and cost assessments followed a superiority design. Participants were 181 adults with RA randomly assigned to either NLC or rheumatologist-led care (RLC), both arms carrying out their normal practice. The primary outcome was the disease activity score (DAS28) assessed at baseline, weeks 13, 26, 39 and 52; the non-inferiority margin being DAS28 change of 0.6. Mean differences between the groups were estimated controlling for covariates following per-protocol (PP) and intention-to-treat (ITT) strategies. The economic evaluation (NHS and healthcare perspectives) estimated cost relative to change in DAS28 and quality-adjusted life-years (QALY) derived from EQ5D. <h3>Results</h3> Demographics and baseline characteristics of patients under NLC (n=91) were comparable to those under RLC (n=90). Overall baseline-adjusted difference in DAS28 mean change (95% CI) for RLC minus NLC was −0.31 (−0.63 to 0.02) for PP and -0.15 (−0.45 to 0.14) for ITT analyses. Mean difference in healthcare cost (RLC minus NLC) was £710 (−£352, £1773) and −£128 (−£1263, £1006) for PP and ITT analyses, respectively. NLC was more cost-effective with respect to cost and DAS28, but not in relation to QALY utility scores. In all secondary outcomes, significance was met for non-inferiority of NLC. NLC had higher 'general satisfaction' scores than RLC in week 26. <h3>Conclusions</h3> The results provide robust evidence to support non-inferiority of NLC in the management of RA. <h3>Trial registration</h3> ISRCTN29803766
Snoring detection during auto-nasal continuous positive airway pressure
Authors: F. Lofaso, K. Leroux, M.A. Quera-Salva, G. Mroue, M.P. D'Ortho, D. Isabey, B. Louis
Journal: European Respiratory Journal (2002)

A bench study using an artificial lung model was performed to evaluate the snoring detection sensitivity of six (commercially available) auto-nasal continuous positive airway pressure (NCPAP) devices. Snoring was simulated by a loudspeaker connected to the lung model and abruptly activated during 1 s of each inspiratory period to induce pressure oscillation. The oscillation frequencies chosen were 30, 60, 90, and 120 Hz. For each frequency, the amplitude of the pressure oscillation produced by the loudspeaker was adjusted to find the threshold at which the auto-nCPAP devices detected snoring. Differences in pressure-amplitude thresholds of up to three-fold were found across auto-nCPAP devices. A randomized clinical study to compare the effects of the least sensitive (Virtuoso LX; Respironics, Nantes, France) and one of the most sensitive, (Goodknight 418A; Malinckrodt, Nancy, France) devices, in two groups of six patients with obstructive sleep apnoea syndrome was then conducted. Goodknight 418A was more sensitive than Virtuoso LX for detecting snoring (mean±sd 92±11% versus 50±39% respectively, p=0.03). To conclude, striking differences exist between auto-nasal continuous positive airway pressure devices in sensitivity for detecting snoring.
Pharmacologic Therapy for Anal Fissure
Authors: Robert D. Madoff
Journal: New England Journal of Medicine (1998)

It has been said that all patients with anorectal symptoms come to the doctor reporting hemorrhoids or worrying about cancer. Among the myriad other diagnostic possibilities, one of the most common is anal fissure. This small tear in the anal skin just at or inside the anal verge typically causes symptoms of severe pain after defecation and bright red rectal bleeding. Anal fissures are easy to diagnose by taking a history and performing an appropriate physical examination — visualizing a sentinel skin tag and everting the anal canal by opposing traction of the patient's buttocks — and easier still for . . .
Introducing The Clinical Connection
Authors: Kenneth C. Anderson
Journal: Clinical Cancer Research (2007)

There have been remarkable recent advances in oncogenomics of cancer, which have allowed enhanced understanding of disease pathogenesis. Each issue of Clinical Cancer Research reflects this progress, with original reports describing novel insights into human cancer biology and pathophysiology, usually in the context of a particular disease setting. The goal of our newest feature, The Clinical Connection, which is appearing for the first time in this issue, is to explain and appraise the potential clinical use and relevance of the findings reported in an original research article within the same issue of the journal. For example, it may describe current and future implications of the reported original observations for improved diagnosis, prognosis, and patient selection, or focus on therapy and assessment of mechanisms of response. Specific emphasis will be placed on implications of the original findings for other cancers, with a goal of improved practice of medicine as a result. Progress in one area will be placed into a broader clinical context in order to ensure that advances in one disease setting can be exploited in another, or in cancer more generally. The Clinical Connection will ensure both a broader appreciation of the clinical implications of original findings and fast forward their bench-to-bedside translation. In this issue, Jinushi and Dranoff make the important first connection with their discussion of “the intimate connections between angiogenesis and tumor immunity and highlight the considerable clinical potential for combination therapies” (Jinushi and Dranoff, p. 3762).
Published death rates may distort work of Scottish surgical “heroes”
Authors: Bryan Christie
Journal: BMJ (2006)

Mortality data have been published for every surgeon in Scotland for the first time, leading to concern about how the public might interpret the information.

The health service in Scotland has been forced to publish the data under freedom of information legislation. Two newspapers had successfully appealed a decision by the Scottish health service to refuse to make the information public ( BMJ 2005;331: 1424).

The information, which was made available on a website earlier this week, relates to around 1000 surgeons. It lists their name, specialty, the type of admission (elective or emergency), and the number of deaths of patients and …
Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab
Authors: F. Peintinger, A.U. Buzdar, H.M. Kuerer, J.A. Mejia, C. Hatzis, A.M. Gonzalez-Angulo, L. Pusztai, F.J. Esteva, S.S. Dawood, M.C. Green, G.N. Hortobagyi, W.F. Symmans
Journal: Annals of Oncology (2008)
ID1 Enhances Docetaxel Cytotoxicity in Prostate Cancer Cells through Inhibition of p21
Authors: Hao Geng, Brooks L. Rademacher, Janet Pittsenbarger, Chung-Ying Huang, Christopher T. Harvey, Marie C. Lafortune, Anne Myrthue, Mark Garzotto, Peter S. Nelson, Tomasz M. Beer, David Z. Qian
Journal: Cancer Research (2010)

Abstract To identify potential mechanisms underlying prostate cancer chemotherapy response and resistance, we compared the gene expression profiles in high-risk human prostate cancer specimens before and after neoadjuvant chemotherapy and radical prostatectomy. Among the molecular signatures associated with chemotherapy, transcripts encoding inhibitor of DNA binding 1 (ID1) were significantly upregulated. The patient biochemical relapse status was monitored in a long-term follow-up. Patients with ID1 upregulation were found to be associated with longer relapse-free survival than patients without ID1 increase. This in vivo clinical association was mechanistically investigated. The chemotherapy-induced ID1 upregulation was recapitulated in the prostate cancer cell line LNCaP. Docetaxel dose-dependently induced ID1 transcription, which was mediated by ID1 promoter E-box chromatin modification and c-Myc binding. Stable ID1 overexpression in LNCaP increased cell proliferation, promoted G1 cell cycle progression, and enhanced docetaxel-induced cytotoxicity. These changes were accompanied by a decrease in cellular mitochondria content, an increase in BCL2 phosphorylation at serine 70, caspase-3 activation, and poly(ADP-ribose) polymerase cleavage. In contrast, ID1 siRNA in the LNCaP and C42B cell lines reduced cell proliferation and decreased docetaxel-induced cytotoxicity by inhibiting cell death. ID1-mediated chemosensitivity enhancement was in part due to ID1 suppression of p21. Overexpression of p21 in LNCaP-ID1–overexpressing cells restored the p21 level and reversed ID1-enhanced chemosensitivity. These molecular data provide a mechanistic rationale for the observed in vivo clinical association between ID1 upregulation and relapse-free survival. Taken together, it shows that ID1 expression has a novel therapeutic role in prostate cancer chemotherapy and prognosis. Cancer Res; 70(8); 3239–48. ©2010 AACR.
Shifting the Disease Management Paradigm From Glucose
Authors: Alin Stirban, Diethelm Tschoepe, Bernd Stratmann
Journal: Diabetes Care (2009)

With the worldwide growing prevalence of obesity and type 2 diabetes, cardiovascular disease (CVD), diabetic nephropathy, retinopathy, and neuropathy as principal complications of diabetes are expected to become a major public health challenge. Diabetes accounts for at least double the number of death rates compared with otherwise healthy individuals. Hyperglycemia represents the hallmark of diabetic metabolic changes, but whether antihyperglycemic treatment alone is sufficient to prevent cardiovascular and other organic complications in type 2 diabetes is a matter of debate.

A recent meta-analysis of epidemiological studies reported an 18% increase in CVD risk for every 1% increase in A1C (1). Two major studies have underlined the importance of optimal glycemic control in reducing diabetes-related complications. The U.K. Prospective Diabetes Study (UKPDS) showed that intensive glycemic control (mean A1C below 7%) by means of insulin or oral agents in type 2 diabetic patients reduces the relative risk for microvascular outcomes by 25% over a period of 10 years (relative risk reduction). The reduction in macrovascular end points (myocardial infarction) was of borderline significance (16% relative risk reduction, P = 0.052) (2). The Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) trial reported a 50% reduction in CVD outcomes in type 1 diabetic patients treated intensively over a period of 6.5 years and followed for a further 12 years (3). In contrast to these data, the intensive glucose-lowering arm of the Action to Control Cardiovascular Risk (ACCORD) trial—a major trial in type 2 diabetic patients—has been recently stopped because of increased mortality in this group (4). The ACCORD trial was set up to test three complementary medical treatment strategies for type 2 diabetes to reduce CVD morbidity and mortality. Aggressive reduction of A1C below 6%, combined increase in HDL cholesterol, and reduction of LDL cholesterol and lowering of blood …
878 IGA ISOTYPE SPECIFIC ANTI-B2GPI ANTIBODIES IN PATIENTS WITH AUTOIMMUNE LIVER DISEASES
Authors: S. Gabeta, G.L. Norman, N. Gatselis, C. Liaskos, P.A. Papamichalis, A. Garagounis, K. Zachou, E.I. Rigopoulou, G.N. Dalekos
Journal: Journal of Hepatology (2008)
Osteopontin regulates human glioma cell invasiveness and tumor growth in mice
Authors: H.-J. Jan, C.-C. Lee, Y.-L. Shih, D.-Y. Hueng, H.-I Ma, J.-H. Lai, H.-W. Wei, H.-M. Lee
Journal: Neuro-Oncology (2009)

Human malignant glioma cells are characterized by local invasion. In the present study, we investigated the role of osteopontin (OPN) in the invasiveness of human glioma cells isolated from grade IV tumors. We found that the expression levels of OPN in these cell lines paralleled matrix metalloproteinase-2 (MMP-2) expression and cell invasiveness potential. When U87MG glioma cells (with a high-OPN expression level) were stably transformed with specific small hairpin RNA to knock down OPN expression, MMP-2 secretion, cell invasiveness, and tumor growth in implanted brains were dramatically reduced. Conversely, forced expression of OPN in GBM-SKH glioma cells (which expressed OPN at a low level) increased MMP-2 secretion, enhanced cell invasiveness, and increased tumor growth in a rodent xenograft model. Expression of OPN was associated with increased expression of vimentin and decreased expression of glial fibrillary acidic protein. Treatment of glioma cells with 5-aza-2′-deoxycytidine (5-aza-dC) suppressed OPN expression in a concentration-dependent manner. Suppression of OPN expression by 5-aza-dC was associated with reductions in MMP-2 secretion, vimentin expression, cell invasion, intravasation, and tumor growth. These data suggest that OPN may play important roles in regulating cell invasion in glioma cells and that 5-aza-dC may serve as a therapeutic agent for human gliomas.
Science and the Paralympic movement
Authors: Walter R Thompson, Yves C Vanlandewijck
Journal: British Journal of Sports Medicine (2013)

Between May 1 and 4 of this year, scientists, athletes, coaches and sport administrators came together in Bonn, Germany for the VISTA2013 Conference. VISTA is held every 2 years in an attempt to have substantial conversations about a topic chosen by the organisers, the Sports Science Committee of the International Paralympic Committee (IPC). Previous VISTA Conferences have included topics on athlete classification, sport performance, women in sport, the athlete with high-support needs, looked at from different disciplinary perspectives. VISTA2013 had the theme ‘Equipment & Technology in Paralympic Sports’. It was a particularly important topic because of the recently accelerated advancements such as in carbon fibre running prostheses (blades) and racing wheelchairs.

Keynote speakers for VISTA2013 included Brendan Burkett who is a member of the IPC Sports Science Committee and professor in Biomechanics at the Faculty of Science, Health, Education and Engineering of the University of the Sunshine Coast, Brisbane, Australia who spoke on Paralympic sporting equipment: Performance enhancement …
The Gravity of Weight: A Clinical Guide to Weight Loss and Maintenanceby KarasuSylvia R., M.D., and KarasuT. Byram, M.D., Foreword by Albert J. Stunkard, M.D. Washington, DC, American Psychiatric Publishing, 2010, 518 pp., $64.00.
Authors: Marsha D. Marcus
Journal: American Journal of Psychiatry (2011)
The Canadian Methotrexate and Etanercept Outcome Study: a randomised trial of discontinuing versus continuing methotrexate after 6 months of etanercept and methotrexate therapy in rheumatoid arthritis
Authors: Janet E Pope, Boulos Haraoui, J Carter Thorne, Andrew Vieira, Melanie Poulin-Costello, Edward C Keystone
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To determine if withdrawing methotrexate (MTX) after 6 months of combination etanercept (ETN)+MTX, in MTX-inadequate responders with active rheumatoid arthritis (RA), is non-inferior to continuing ETN+MTX. <h3>Methods</h3> Tumour necrosis factor-inhibitor naïve RA patients with disease activity score 28 (DAS28)≥3.2, swollen joint count≥3, despite stable MTX, were treated with ETN+MTX for 6 months, followed by randomisation to either continue ETN+MTX or switch to ETN monotherapy for an additional 18 months. The primary endpoint was change in DAS28 from 6-month randomisation to 12 months. The non-inferiority margin of change in DAS28 was 0.6, with prespecified analyses (DAS28&lt;3.2 vs DAS28≥3.2). <h3>Results</h3> 205 patients were randomised. DAS28 was stable in patients on ETN+MTX and increased slightly in patients on ETN monotherapy from 6 to 12 months. Non-inferiority was not achieved, with an adjusted difference of 0.4 (0.1 to 0.7) between the ETN and the ETN+MTX groups, for the month 6–12 change in DAS28. However, patients who achieved low disease activity (LDA; DAS28&lt;3.2) at 6 months had a similar disease activity at 12 months, whether on monotherapy or combination therapy (DAS28 change 0.7 ETN vs 0.57 ETN+MTX, p=0.8148). Conversely, for patients who did not reach LDA at 6 months, those on ETN monotherapy had increased disease activity at 12 months, while disease activity continued to decrease for patients on combination therapy, at 12 months (DAS28 change 0.4 ETN vs −0.4 ETN+MTX, p=0.0023). <h3>Conclusions</h3> Non-inferiority was not achieved. Withdrawing MTX after 6 months of continuation ETN+MTX in MTX inadequate responders did not yield the same degree of improvement between 6 and 12 months compared with continuing ETN+MTX. <h3>Trial Registration</h3> ClinicalTrials.gov−NCT00654368.