tbuckley/cabot-search huggingface dataset:
Abstract 16227: Safety and Effectiveness of Dabigatran Relative to Warfarin in Routine Care
Authors: John D Seeger, Dorothee B Bartels, Krista Huybrechts, Katsiaryna Bykov, Dalia Shash, Kristina Zint, Sebastian Schneeweiss
Journal: Circulation (2014)

Introduction:  It is important to quantify the comparative safety and effectiveness of new drugs in routine care.   Hypothesis:  To assess the safety and effectiveness of dabigatran compared to warfarin in a sequential long-term study program in patients in routine care.   Methods:  This program uses 2 large commercial US health insurance databases and propensity score matching to compare new users of dabigatran and warfarin with respect to ischemic and bleeding events, with planned interim analyses.   Results:  From Oct 2010 through Dec 2012 patients with non-valvular atrial fibrillation and CHA 2 DS 2 -VASc scores ≥1 who initiated dabigatran, were matched (1:1) to warfarin initiators using a propensity score that balanced known risk factors for ischemic and bleeding events (Table). Follow-up until discontinuation of the anticoagulant, outcome event, or disenrollment was an average of 5 months (dabigatran) and 4 months (warfarin). Interim results indicate a 23% stroke rate reduction by dabigatran in a pooled analysis: HR=0.77, 95% CI=0.55-1.09. In the larger MarketScan database alone the stroke reduction was 36% (HR=0.64, 95% CI=0.44-0.95). There were only 26 strokes in the smaller Optum database leading to wide confidence intervals: HR=1.62, 95% CI=0.72-3.66. There was a 25% reduction in the rate of major hemorrhage: pooled HR=0.75, 95% CI=0.65-0.87 (MarketScan: HR=0.78 (95% CI=0.67-0.91), Optum: HR=0.56 (95% CI = 0.36-0.86)).   Conclusions:  Interim results from this sequential long-term study program of patients in routine care suggest that dabigatran has improved effectiveness and safety relative to warfarin. Results highlight the limitations of small event numbers, e.g. stroke in anticoagulated patients, in early stages of post-marketing monitoring programs making chance a likely explanation for variations in point estimates between databases. Assessments of effectiveness beyond the first six months of therapy are limited by the short average follow-up.
Abstract 14767: Integrated Telehealth and Care Management Program Reduces All Cause Mortality in Medicare Beneficiaries with Heart Failure
Authors: Robert L Page, David P Kao, Dendy Macaulay, Howard G Birnbaum, John Jarvis, Urvi Desai, JoAnn Lindenfeld
Journal: Circulation (2012)

Background: Fragmented delivery systems and lack of continuity of care are potential barriers to the effective treatment of patients with heart failure (HF). Benefits of telehealth technology on mo...
Maladaptive cognitive structures in depression
Authors: Maria Kovacs, Aaron T. Beck
Journal: American Journal of Psychiatry (1978)

According to the cognitive view, the individual's negative and distorted thinking is the basic psychological problem in the depressive syndrome. The distorted cognitions are supported by maladaptive cognitive schemata, which involve immature "either-or" rules of conduct or inflexible and unattainable self-expectations. These schemata are probably acquired early in development and, if uncritically carried into adulthood, serve to predispose the individual to depression. Since these schemata are long-term identifiable psychological patterns that influence attitude and behavioral responses, they may constitute a cognitive dimension of the depression-prone individual's personality. The authors discuss the treatment implications of the cognitive approach to depression.
The first thoracic triumvirate
Authors: Nicholas Hart, Gisli Jenkins, Alan Smyth
Journal: Thorax (2015)

An editorial board delivering basic science, translational science and clinical trials across paediatrics and adults 

We are incredibly proud and honoured to accept the position of Editors-in-Chief of Thorax. Thorax is the premier respiratory journal in the UK, and the official journal of the British Thoracic Society (BTS). It currently has an impact factor of 8.29, making it the third highest ranked respiratory journal in the world. We believe that Thorax has for many years reflected the strength of the British respiratory community publishing wide-ranging, high-calibre research across the translational spectrum. This view is supported by metrics showing that the UK has the highest H factor within Europe and the second highest H factor in the world after the USA. Furthermore, the UK is the third most cited country in the world, after the USA and China. The strong association with the BTS has been a major strength of the Journal because it represents the clinicians, clinical academics and scientists within respiratory medicine in the UK. We have ‘grown up’ with Thorax and the BTS and have seen how the Journal has grown from strength to strength under the strong, astute editorial guidance …
Abstract 4121: Clomipramine Infusion During Tilt Test To Imply The Neurocardiogenic Origin Of Syncopes And Presyncopes Of Unknown Aetiology
Authors: Gael Cinquetti, Eric Perrier, Jacques Deroche, Olivier Manen, Michel Lerecouvreux, Charlotte De Serre De Saint Roman, Christian Plotton, Roland Carlioz
Journal: Circulation (2008)

The aim of this study was to prospectively evaluate the diagnostic accuracy for neurocardiogenic syncopes (NCS) of two Head-Up Tilt table test (HUT) strategies in 991 patients with syncopes/presyncopes of unknown aetiology after negative clinical and non invasive investigations. HUT is a widely accepted tool in the evaluation of patients with evidence of VVS but questions remain about the sensitivity and the use of provocative agents.Clomipramine (CP), a serotonin re-uptake inhibitor, was recently proposed as a new drug challenge test for the diagnosis of neurocardiogenic syncope (NCS). Group A : the first 341 pts (207 male ; mean age = 49,9 ± 23 years) were passively tilted at 60° for 30 minutes (min), then for 15 min with 2 μg/min isoproterenol infusion rate. Group B : the following 650 pts (383 male ; mean age = 48,3 ± 21 years) were tilted at 60° for 20 min with 5 mg CP infused during the first 5 min of tilt. A positive HUT was defined as reproducting the patient’s syncope or presyncope, associated with an abrupt fall in blood pressure (systolic blood pressure &lt;80 mmHg) and/or concomitant bradycardia (&lt;50 beats/min). Positives responses were classified in 3 types according to the Brignole’s modification of the VASIS classification. There was no significant difference between group A/B in sex or age. Group A : Positive HUT* : 103 (Sensitivity : 30,2%) Group B : Positive HUT* : 382 (Sensitivity : 58,8 %) (*) type 1 : 36 vs 157 ; type 2A : 8 vs 13 ; Type 2B: 9 vs 57 (14,9%) ; Type 3 : 50 vs 155. No adverse effect was noticed. CP during HUT increase significantly the accuracy of the test for NCS diagnosis, especially for type 2B answers, and patients &lt;30 yo. The duration of the test is notably shortened, and the tolerance is remarkable. If previously reported specificity (87 to 94%) was confirmed, CP-HUT might be the most valuable tool in the evaluation of pts with syncopes/presyncopes of unknown aetiology.
Targeting oxidant-dependent mechanisms for the treatment of COPD and its comorbidities
Authors: Ivan Bernardo, Steven Bozinovski, Ross Vlahos
Journal: Pharmacology & Therapeutics (2015)

Chronic obstructive pulmonary disease (COPD) is an incurable global health burden and is characterised by progressive airflow limitation and loss of lung function. In addition to the pulmonary impact of the disease, COPD patients often develop comorbid diseases such as cardiovascular disease, skeletal muscle wasting, lung cancer and osteoporosis. One key feature of COPD, yet often underappreciated, is the contribution of oxidative stress in the onset and development of the disease. Patients experience an increased burden of oxidative stress due to the combined effects of excess reactive oxygen species (ROS) and nitrogen species (RNS) generation, antioxidant depletion and reduced antioxidant enzyme activity. Currently, there is a lack of effective treatments for COPD, and an even greater lack of research regarding interventions that treat both COPD and its comorbidities. Due to the involvement of oxidative stress in the pathogenesis of COPD and many of its comorbidities, a unique therapeutic opportunity arises where the treatment of a multitude of diseases may be possible with only one therapeutic target. In this review, oxidative stress and the roles of ROS/RNS in the context of COPD and comorbid cardiovascular disease, skeletal muscle wasting, lung cancer, and osteoporosis are discussed and the potential for therapeutic benefit of anti-oxidative treatment in these conditions is outlined. Because of the unique interplay between oxidative stress and these diseases, oxidative stress represents a novel target for the treatment of COPD and its comorbidities.
Abstract 15486: Intramyocardial Gene Therapy With a Novel Angiogenic Molecule, Pellino-1 Preserves Functions and Increases Cell Survivability in a Mouse Myocardial Infarction Model
Authors: Vladimir Coca-Soliz, Leonidas Tapias, Vaithinathan Selvaraju, Mahesh Thirunavukkarasu, J.Alexander Palesty, Nilanjana Maulik
Journal: Circulation (2014)

Introduction: Our present study attempted to evaluate the effect of Pellino1 (Peli1) overexpression on angiogenesis and myocardial function by intramyocardial administration of adenovirus encoding Peli1 (Ad.Peli1) following myocardial infarction (MI) in mice. Methods: CD-1/ICR mice were divided into six groups: Control Sham (CS); Control MI (CMI); Adeno-LacZ Sham (Ad.LacZS); Adeno-LacZ MI (Ad.LacZMI); Adeno-Pellino1 Sham (Ad.Peli1S) and Adeno-Pellino1 MI (Ad.Peli1MI). MI was induced by permanent ligation of left anterior descending coronary artery (LAD). Following LAD ligation or sham surgery Ad.LacZ or Ad.Peli1 was injected at 4 border zone sites to either Ad.LacZS/Ad.LaczMI or Ad.Peli1S/Ad.Peli1MI groups respectively. Heart tissue was collected 24 hours post MI for Western blot analysis,4 days for gap junction protein and 30 days later for immunohistochemistry after echocardiographic analysis. Results: Echocardiographic analysis revealed increased ejection fraction [48±0.75 vs. 33±0.98% (n=10-11);p&lt;0.05] and fractional shortening [24±0.49 vs. 16±0.51% (n=10-11) p&lt;0.05] along with decreased LVIDs [3.74±0.14 vs. 5.21±0.19(mm) (n=10-11); p&lt;0.05] in the Ad.Peli1MI as compared to the Ad.LacZMI group. Immunohistochemical analysis for fibrosis with picrosirius red staining exhibited a decrease in collagen deposition in Ad.Peli1MI group [16±1.05 vs. 29±2.05% (n=8); p&lt;0.0001] as compared to Ad.LacZMI group. Connexin-43, a major ventricular gap junction protein was found to be significantly expressed in Ad.Peli1MI group compared to Ad.LacZMI. Ad.Peli1 gene therapy after MI increased capillary density [2342±122 vs. 1776±54 counts/mm2 (n=6);p&lt;0.05] as compared to the Ad.LacZMI group. Western blot analysis 24h after MI revealed increased phosphorylation of Akt (3.4 fold), eNOS (1.9fold) and MK2 (1.7fold) with Ad.Peli1 treatment compared to Ad.LacZ. Similar experiments conducted with Peli1KO mice also revealed decreased DNA binding activity of NFκB activity by Gel-shift analysis 8 h after MI. Conclusion: Taken together, these data shows the potential of Peli1 gene therapy in inducing angiogenesis and reducing ventricular remodeling in the infarcted myocardium.
Phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of PF-00337210, a highly selective VEGFR inhibitor
Authors: G. Liu, P. M. LoRusso, P. Goncalves, K. Holen, A. Traynor, J. Zhang, B. Hee, M. Tortorici, D. R. Shalinsky, A. D. Ricart
Journal: Journal of Clinical Oncology (2009)

3519 Background: PF-00337210 potently inhibits VEGFR2 phosphorylation and is &gt;10-fold more selective, based on IC 50 , for VEGFR2 than other kinases (eg, KIT and PDGFRs). In vitro, PF-00337210 inhibits VEGF-mediated HUVEC survival (IC 50 = 0.53 nM). In vivo, it inhibits tumor angiogenesis and human xenograft growth. Methods: The primary objectives were to determine the safety profile and MTD of PF-00337210. PK and PD (DCE-MRI at baseline and cycle [C] 1, day [D] 2) were also evaluated. The volume rate transfer constant (K trans ) assessed VEGFR inhibitory effects on vascular permeability and perfusion. Results: To date, 29 patients (pts) with advanced solid tumors were treated with PF-00337210 at doses of 0.67–9 mg QD, 13 of whom (45%) had received prior VEGF/VEGFR inhibitors. No dose-limiting toxicities (DLTs) occurred at 0.67–8 mg QD. Two DLTs occurred at 9 mg QD: one pt had chest pain, G3 troponin I, and G3 myocardial ischemia; a second pt had significant hypertension (HTN) at the anticipated T max after the first dose (systolic ≥180 mmHg over 3 hrs). HTN and fatigue were the most common treatment-related adverse events (AEs). HTN occurred in 8 pts (28%); incidence and intensity corresponded with dose, but was well controlled with antihypertensive agents. Fatigue was reported in 9 pts (31%) and occurred most frequently in pts receiving ≥6 mg QD. Other AEs included nausea, anorexia, proteinuria, and diarrhea. PK data indicated that mean (%CV) t 1/2 at 8 mg QD was 8.60 (81) h (n=4) and AUC 0–24 was 309 (45) ng.h/mL at steady-state (SS) on C1D15. Exposures (AUC 0–24 ) were generally linear and variability ranged from 21 to 44% across doses. The observed accumulation ratio (R ac ) at SS was 1.22 (15) (n=21), which was predicted by t 1/2 . PF-00337210 decreased mean K trans (1/min) values by 22.5±11.8 (n=2), 15.2 (n=1), 5.4±4.8 (n=3), and 25.3±8.5% (n=4) at 4, 6, 8, and 9 mg QD, respectively. No objective responses were observed but 7/29 pts (24%) had stable disease. Conclusions: PF-00337210 was well tolerated with the DLTs being HTN and myocardial ischemia. The QD MTD was determined to be 8 mg. Preliminary evidence of VEGFR inhibition was shown by DCE-MRI at ≥4 mg QD. The trial is now evaluating BID dosing which may allow increased drug exposures and fewer hypertensive effects that may be related to C max . [Table: see text]
Abstract P339: Angina and Silent Myocardial Infarction are Associated with Isolated Small Vessel Peripheral Artery Disease in Community-Dwelling Older Adults: The Rancho Bernardo Study
Authors: Jan M Hughes-Austin, Michael H Criqui, Elizabeth Barrett-Connor
Journal: Circulation (2014)

Background: Classic CVD risk factors associated with isolated small vessel peripheral artery disease (iSV-PAD) include older age, male sex, longer smoking duration, and higher LDL cholesterol levels. These CVD risk factors have been linked to atherosclerosis in several vascular beds and to cardiac ischemia. It is not known whether iSV-PAD shares these same links, especially in community-dwelling older adults. Thus, in the Rancho Bernardo (RB) Study, we investigated whether iSV-PAD was associated with measures of atherosclerosis and cardiac ischemia. Methods: Among 965 RB Study participants with complete measures of ankle-brachial index (ABI), toe-brachial index (TBI), and measures of cardiac ischemia [self-reported angina, major Q wave on electrocardiogram (ECG), and any ECG abnormality], we evaluated associations between cardiac ischemia and iSV-PAD. In a subset of 387 RB participants free of diagnosed CVD, we evaluated associations between measures of atherosclerosis [coronary artery calcium (CAC) (Agatston scores and calcium volume) and internal carotid intima-media thickness (cIMT)] with iSV-PAD. Isolated SV-PAD was defined by bilateral normal ABI (1.0-1.4) with bilateral TBI &lt; 0.7. Associations of measures of atherosclerosis and cardiac ischemia with iSV-PAD were evaluated using logistic regression in staged models, adjusted for age, sex, anthropometrics, lifestyle, comorbidities, and medications. Results: More likely to have iSV-PAD were participants who ever had angina (OR=2.1, 95% CI: 1.04-4.2) or had major Q wave on ECG (OR=4.2, 95% CI: 1.1-15.5). There were too few to stratify by sex. No statistically significant associations were observed for measures of atherosclerosis with iSV-PAD. (Figure 1) Conclusion: Strong associations of cardiac ischemia, coupled with null associations of atherosclerosis, with iSV-PAD suggest that iSV-PAD may indicate vascular pathology different from atherosclerosis. Further investigation of endothelial dysfunction and iSV-PAD may elucidate underlying pathology.
Managing demand: Matching demand and supply fairly and efficiently
Authors: D. Pencheon
Journal: BMJ (1998)

This is the first of five articles on ways of managing demand for health care

The challenge of meeting the demand for public services that are free at the point of use is increasing. Examples, in increasing order of complexity and controversy, include water, higher education, road space, and health care. These services are perceived as important to society in general, and demand is rising rapidly and unsustainably.

Such increases in demand can be managed either by reducing the demand—, for example, by charging, as for water or road space—or by increasing the supply—, for example, via increased funding, as with student loans. In health care, perversely, we do the opposite of both these approaches: we fuel demand by failing to manage it—for example, by not curbing expectations—and we are often forced to cut supply through lack of resources.

Demand for health care is undoubtedly rising. The average number of consultations for children in each of the first years of life (even after excluding surveillance and immunisations) has, in one general practice, risen from 3.73 per child in 1960 to 17.2 in 1990.1 We need to understand better how this ever increasing demand for health care is initiated and expressed and use this understanding to manage the whole system better. Professionals have the same increasing expectations from the service as the public does. Managing the pressure on the health service is as much about managing the expectations and rights of professionals to treat as it is about managing the expectations of patients to be treated.

#### Summary points

Demand management is about moving from merely struggling to meet the increasing demand for health services to shaping this demand so that health needs of individuals and populations are best served with the available resources

Managing demand does not only mean reducing it: where …
Arterial Versus Venous Bypass Grafts in Patients With In-Stent Restenosis
Authors: Mario Gaudino, Carlo Cellini, Claudio Pragliola, Carlo Trani, Francesco Burzotta, Giovanni Schiavoni, Giuseppe Nasso, Gianfederico Possati
Journal: Circulation (2005)

Background— In patients who develop in-stent restenosis, successful revascularization can be difficult to achieve using percutaneous methods. This study was designed to verify the surgical results in this setting and to evaluate the potential beneficial role of arterial bypass conduits. Methods and Results— Sixty consecutive coronary artery bypass patients with previous in-stent restenosis and 60 control cases were randomly assigned to receive an arterial conduit (either right internal thoracic or radial artery; study group) or a great saphenous vein graft (control group) on the first obtuse marginal artery to complete the surgical revascularization procedure. At a mean follow-up of 52±11 months, patients were reassessed clinically and by angiography. Freedom from clinical and instrumental evidence of ischemia recurrence was found in 19 of 60 subjects in the study group versus 45 of 60 in the control series ( P =0.01). The results of the arterial grafts were excellent in both the study and control groups (right internal thoracic artery patency rate, 19 of 20 for both, and radial artery patency rate, 20 of 20 versus 19 of 20; P =0.99). Saphenous vein grafts showed lower patency rate than arterial grafts in both series and had extremely high failure rate in the study group (patency rate, 10 of 20 in the study group versus 18 of 20 in the control group; P =0.001). Use of venous graft was an independent predictor of failure in the study group, whereas hypercholesterolemia was associated with graft failure in both series. Conclusions— Venous grafts have an high incidence of failure among cases who previously developed in-stent restenosis, whereas the use of arterial conduits can improve the angiographic and clinical results. Arterial grafts should probably be the first surgical choice in this patient population.
Abstract MP65: Fish Consumption and Acute Coronary Syndrome: A Meta-Analysis
Authors: Sylvie S Leung Yinko, Ken D Stark, George Thanassoulis, Louise Pilote
Journal: Circulation (2014)

Background: While findings on omega-3 supplements in cardiovascular diseases (CVD) are controversial, various studies suggest that fish consumption may be beneficial to cardiovascular health and reduce the risk of acute coronary syndrome (ACS). The purpose of this study was to investigate the association between fish consumption and ACS by conducting a dose-response meta-analysis. Methods: We conducted a literature search of Medline and Embase databases from 1966 to June 2013 for prospective cohort and case-control studies that evaluated the association between fish consumption and ACS among general populations without CVD history. Additional studies were identified via hand search of references of relevant articles. Estimates of relative risk (RR) were pooled using random effects model. Sex and age effects were also evaluated. Results: Our search retrieved 11 prospective cohort and 8 case-control studies, totaling 408,305 participants. Among prospective cohort studies, the highest category of fish consumption, i.e. ≥4 times per week, was associated with the greatest risk reduction in ACS (RR 0.79, 95% CI 0.70-0.89). Among case-control studies, fish consumption also appeared to reduce ACS risk (RR 0.76, 95% CI 0.67-0.87 for 1 to &lt;2 times per week). In dose-response analysis, each additional 100 g serving of fish per week was associated with a 5% reduced risk (RR per serving 0.95, 95% CI 0.92-0.97). Subgroup analysis and meta-regression suggested that the risk reduction did not differ across sex or age groups. Conclusions: Our meta-analysis demonstrated that there is an inverse association between fish consumption and ACS risk. Fish consumption appears beneficial in the primary prevention of ACS and higher consumption was associated with higher protection.
“Targeting the Heart” in Heart Failure
Authors: Jane E. Wilcox, Gregg C. Fonarow, Hossein Ardehali, Robert O. Bonow, Javed Butler, Andrew J. Sauer, Stephen E. Epstein, Sadiya S. Khan, Raymond J. Kim, Hani N. Sabbah, Javier Díez, Mihai Gheorghiade
Journal: JACC Heart Failure (2015)
Armed antibodies targeted to STEAP1 inhibit growth of human prostate xenografts in vivo
Authors: Tracey McKenna, Jennifer Batson, Sarajane Ross, Paul Polakis, Bonnee Rubinfeld
Journal: Cancer Research (2007)

4468  Highly restricted expression patterns for cell surface antigens make them ideal candidates for targeted delivery of cytotoxic agents by specific monoclonal antibodies (′armed′ antibodies). STEAP1, six transmembrane epithelial antigen of the prostate, is one such antigen whose expression is highly localized to the prostate with minimal expression in other normal tissues. An antibody generated against the extracellular epitopes of STEAP1 recognizes STEAP1 on the cell surface of prostate cancer cell lines. This antibody, when armed with the auristatin microtubule destabilizing agents MMAE or MMAF, demonstrated potent efficacy in multiple established mouse xenograft models derived from prostate cancer cell lines or from patient derived prostate models. These results suggest that armed STEAP1 antibodies may be a promising therapeutic for the treatment of prostate cancer.
Persistent neonatal thrombocytopenia can be caused by IgA antiplatelet antibodies in breast milk of immune thrombocytopenic mothers
Authors: Hagit Hauschner, Nurit Rosenberg, Uri Seligsohn, Rafael Mendelsohn, Aryeh Simmonds, Yakov Shiff, Yaakov Schachter, Shraga Aviner, Nechama Sharon
Journal: Blood (2015)