tbuckley/cabot-search huggingface dataset:
Cutaneous malignant melanoma in Scotland: incidence, survival, and mortality, 1979-94
Authors: R. M MacKie, D. Hole, J. A A Hunter, R. Rankin, A. Evans, K. McLaren, M. Fallowfield, A. Hutcheon, A. Morris
Journal: BMJ (1997)

To determine the changing incidence of and mortality from cutaneous malignant melanoma in Scotland from 1979 to 1994.Detailed registration of clinical and pathological features, surgical and other treatment, and follow up of all cases of cutaneous malignant melanoma diagnosed from 1979 to 1994 and registered with specialist database for Scotland.Scotland.6288 patients with invasive primary cutaneous malignant melanoma diagnosed between 1 January 1979 and 31 December 1994.The annual age standardised incidence of cutaneous malignant melanoma rose significantly from 3.5 to 7.8 per 100,000 per year in men and from 6.8 to 12.3 per 100,000 per year in women (P < 0.001 for both). World standardised rates increased from 2.7 to 6.0 per 100,000 per year in men and 4.6 to 8.50 per 100,000 in women. The incidence of melanoma continued to increase significantly in men of all ages during the study, but the rate stabilised in women after 1986. Mortality from cutaneous malignant melanoma was 1.3 per million per annum in men in 1979, rising to 2.3 per million per annum in 1994 (P < 0.01); it was 2.4 per million per annum in women in 1979, falling to 1.9 per million per annum in 1994 (P = 0.09). The underlying mortality trends showed a continuing rise for men but a downward trend for women that was not significant (P = 0.09). In men, melanoma free survival was 69% at 5 years and 61% at 10 years; in women the corresponding rates were 82% and 75%. Younger patients had higher survival rates, which were not entirely explained by thinner tumours. Over the 15 year period, survival rates improved by 12% overall, only partly owing to thinner tumours.In Scotland the incidence of melanoma in women has stabilised, while mortality associated with melanoma in women shows a downward trend.
Abstract 9918: Novel and Profound Lipid Effects of GSK1292263, a Potent and Selective GPR119 Agonist, in Dyslipidemic Subjects
Authors: Derek J Nunez, Mark Bush, David Collins, Susan McMullen, Dawn Gillmor, Gerri Poss, Robert Schott, Paul Feldman
Journal: Circulation (2012)

GSK1292263 (GSK263), a GPR119 agonist, improves glucose regulation in animal models of diabetes, but has no effect on plasma glucose in type 2 diabetics. Unexpectedly, GSK263 lowered fasting LDLc and triglycerides (TG), while increasing HDLc in these diabetic subjects. The study aim was to determine whether GSK263 improves lipid profiles in dyslipidemic, non-diabetic subjects when dosed alone or with atorvastatin (NCT# 01218204). Eligible subjects on statin/Vytorin therapy were washed off these drugs for 4 weeks. After washout, they were randomized to receive (i) 100mg (n=11), 300mg (n=12) or 800mg (n=13) QD of GSK263 or placebo (n=11) for 2 weeks; or (ii) 10mg atorvastatin (A10) or 80mg atorvastatin (A80) for a 4-week Run-in period. After the atorvastatin Run-in, (i) A10 was co-dosed with: 100mg (n=11), 300mg (n=11), 800mg (n=11) QD GSK263, placebo (n=12) or 10mg ezetimibe (n=13), and (ii) A80 was co-dosed with: 800mg (n=12) QD GSK263 or placebo (n=13). Fasting plasma lipids and NMR lipoprotein particles (LipoProfile) were measured at baseline and after 2 weeks of dosing. By ANCOVA (change from baseline), 800mg GSK263 significantly increased fasting HDLc by 20.7% (95% CI 9.8 to 31.6%), reduced fasting LDLc by 21.8% (95% CI -32.1 to -11.2%), and reduced fasting TGs by 54.8% (95% CI -70.8 to -38.9%) when compared to placebo. TG AUCs (wm 0-24h) fell by 41.3% (95% CI -61.9 to -20.8%). Similar effects were seen when co-dosed with A10 and A80. The lipid effects were dose-dependent, with GSK263 100mg having minimal effect. GSK263 may reduce apoB100, apoE and CRP, but had no clear effect on apoA1. NMR analysis suggests that GSK263 (i) reduced VLDL and chylomicron particle number and VLDL particle size, (ii) reduced LDL and IDL particle number and increased LDL particle size, and (iii) increased HDL particle number and size, especially when co-administered with atorvastatin. GSK263 was generally well tolerated over the dose range of 100mg to 800mg QD administered for 14 days. The majority of AEs associated with GSK1292263 were mild in intensity. GSK263 has significant effects on plasma lipids and lipoprotein particles in dyslipidemic patients when dosed alone and with atorvastatin. Studies are on-going to investigate the novel mechanisms underlying these lipid effects.
Reperfusion in acute myocardial infarction
Authors: N. M Robinson
Journal: BMJ (2000)

Acute myocardial infarction is usually caused by occlusive coronary thrombosis initiated by rupture of an atheromatous plaque. The subendocardium infarcts early after coronary occlusion, but outward extension to affect the full thickness of the ventricular wall may take several hours. Restoration of normal coronary flow, before the transmural spread of infarction is complete, is now seen as the primary goal of hospital treatment because it allows reperfusion of the threatened myocardium with reduction of eventual infarct size.

The best established method of restoring coronary flow is treatment with thrombolytic agents, but angioplasty, with or without the insertion of a stent, is fast gaining exponents. Thrombolytic therapy is the best tested and most widely used means of achieving this goal and among eligible patients produces coronary recanalisation in about 60-80% of cases,1 2 depending on the agent used. Beneficial effects on survival have been confirmed in several studies.3 4

Nevertheless, thrombolytic therapy has important limitations because normal coronary flow is achieved in only …
Abstract 246: The Impact of ECG Filtration Software on Minimizing the Interval to Defibrillation for Inpatient Cardiopulmonary Arrest
Authors: Ruchika D Husa, Rebecca Sell, Daniel P Davis
Journal: Circulation (2011)

Background: Minimizing pre- and post-shock compression pauses improves the likelihood of successful defibrillation. However, rhythm analysis prior to and immediately following defibrillation attempts may prolong these intervals. ECG filtration software may decrease pre- and post-shock pause intervals. Objective: To describe the impact of ECG filtration software in minimizing pre- and post-shock pauses for inpatient cardiopulmonary arrest (CPA). Methods: This study was conducted in two urban university hospitals following implementation of ECG filtration software in May 2009. We routinely export defibrillator data from all CPAs. For this analysis, pre- and post-shock compression pauses were quantified. In addition, two physicians independently evaluated the pre-shock rhythm. This data was reported descriptively. Results: A total of 98 defibrillation attempts in 38 patients were included. Pre-shock intervals ranged from 0-39 seconds; the majority (75%) were &lt;5 sec. The vast majority (94%) of post-shock intervals were &lt;5 sec. The majority (63%) of pre-shock rhythms were ventricular fibrillation/ventricular tachycardia; 23% were pulseless electrical activity (PEA); 3% were asystole; and 10% could not be determined. For PEA defibrillation attempts, 74% had a pre-shock pause &lt;2 sec, and 26% were administered at the end of prolonged codes. Mean chest compression fraction (CCF) were 89%. Conclusions: ECG filtration software appears to minimize pre- and post-shock intervals. A small but measurable incidence of PEA defibrillation was observed with very brief pre-shock intervals. This may warrant a brief pause to confirm VF/VT prior to defibrillator charge.
Proposal for routine antenatal screening at 14 weeks for hepatitis B surface antigen
Authors: P M Grosheide, J W Wladimiroff, R A Heijtink, J A Mazel, G C M L Christiaens, A S M Nuijten, S W Schalm
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To develop a low cost, high compliance screening programme for identification of carriers of hepatitis B surface antigen in the obstetric population of the Netherlands. <b>Design</b>: A seven year open, descriptive study of screening for hepatitis B surface antigen as part of routine prenatal laboratory testing at 14 weeks of gestation. Compliance with programme evaluated by checking delivery records (hospitals) or registration of births in the 30 participating municipalities (rural area). <b>Setting</b>: Three large city hospitals (two tertiary referral centres) and one rural area with a large number of home deliveries. <b>Subjects</b>: 99706 pregnant women applying for prenatal care for the first time. <b>Main outcome measures</b>: Proportion of pregnant women routinely screened; prevalence of hepatitis B surface antigen in large cities and rural area. <b>Results</b>: Uptake of screening reached 97% in the hospitals after inclusion of 10% screened at delivery; the estimated uptake in the rural area was &gt;95%. Prevalence of hepatitis B surface antigen was 1.6% in the large cities and 0.3% in the rural area. For screening at delivery the prevalence was 2.5 times higher (4%, P&lt;0.01) than for screening at week 14 of gestation. <b>Conclusion</b>: Incorporation of universal testing for hepatitis B surface antigen into routine prenatal laboratory testing is practical; high compliance is achieved when screening is supplemented with rapid screening at delivery for those who escaped routine prenatal care.
18F-4V for PET–CT Imaging of VCAM-1 Expression in Atherosclerosis
Authors: Matthias Nahrendorf, Edmund Keliher, Peter Panizzi, Hanwen Zhang, Sheena Hembrador, Jose-Luiz Figueiredo, Elena Aikawa, Kimberly Kelly, Peter Libby, Ralph Weissleder
Journal: JACC. Cardiovascular imaging (2009)
Fasting Triglycerides Predict Recurrent Ischemic Events in Patients With Acute Coronary Syndrome Treated With Statins
Authors: Gregory G. Schwartz, Markus Abt, Weihang Bao, David DeMicco, David Kallend, Michael Miller, Hardi Mundl, Anders G. Olsson
Journal: Journal of the American College of Cardiology (2015)
Abstract P265: Physical Activity is Inversely Associated with Multimorbidity in Men: Results from the Population-Based KORA-Age Augsburg Study
Authors: Christine S Autenrieth, Inge Kirchberger, Margit Heier, Anja Zimmermann, Annette Peters, Barbara Thorand, Angela Döring
Journal: Circulation (2012)

Background: The co-occurrence of two or more chronic diseases in one individual, commonly known as multimorbidity, has become a major public health problem among the elderly. Physical activity has proven to be an essential means to mitigate chronic morbidity and disability. Therefore, we hypothesized that physical activity was inversely associated with multimorbidity. Currently, epidemiological studies addressing this research question are lacking. Methods: Using data from 1,007 men and women aged 65–94 years who participated in the population-based KORA-Age project conducted in Augsburg/Germany and two adjacent counties in 2009, thirteen chronic conditions were identified through a standardized telephone interview and a self-administered questionnaire. Physical activity scores were calculated based on the self-reported physical activity scale for the elderly (PASE), comprised of occupational, household and leisure activity items. Sex-specific logistic regression adjusted for age, BMI, education, and nutritional status was applied to determine the relation of the continuous physical activity score and multimorbidity (yes/no). Results: Multimorbidity was prevalent in 62.3% and 68.5% for men and women, respectively. Physical activity (mean PASE score ± SD) was higher in men (125.1 ± 59.2) than in women (112.2 ± 49.2). Among men, the OR for multimorbidity was 0.57 (95% CI: 0.41–0.78) for a 100-unit increase in the PASE score. No significant results could be observed for women (OR: 1.17; 95% CI: 0.73–1.89) (p-value for sex interaction=0.271). Additional analyses of physical activity quartiles showed that the effect among men were mainly observed in the highest quartile versus the lower ones (Figure 1). Conclusion: Our data suggest an inverse association between physical activity and multimorbidity in men, but not in women. Physical activity may counteract the development or progression of chronic diseases in men; further large population-based studies are needed to explore the possible sex-differences.
Abstract 1657: Binding and Uptake of Oxysterols by Vascular Smooth Muscle Cells through the Cluster of Differentiation (CD)-1d Protein
Authors: Corina Rosales, Daming Tang, Yong-Jian Geng
Journal: Circulation (2006)

Background– The MHC-class I-like molecule, CD1d, might play a role in lipid antigen presentation implicated in atherogenesis due to its hydrophobic binding pockets. Interestingly, CD1d is expressed...
Efficacy and safety of gefitinib in chemo-naive patients with non-small cell lung cancer (NSCLC) in an expanded access program (EAP)
Authors: R. B. Reiling, R. Natale, J. Wade, R. Herbst, T. Hensing, C. P. Belani, K. Kelly, J. Ochs, R. Govindan, A. Wozniak, A. Krebs
Journal: Journal of Clinical Oncology (2005)

7094 Background: Patients (pts) with advanced NSCLC who cannot tolerate or refuse chemotherapy (CT) have few or no treatment options. The EGFR-TKI gefitinib (Iressa) has antitumor activity and favorable tolerability in pts with recurrent advanced NSCLC. A global EAP made gefitinib available to >37,000 pts with NSCLC who had failed standard treatment or were ineligible for or refused cytotoxic CT. Methods: Retrospective chart review of 1671 pts enrolled at 11 sites in the US EAP identified 198 pts (89 men, 109 women, median age 72.7 y [range 37.8–89.9 y]) who had not received prior CT for advanced NSCLC. Pts received 250 mg/d gefitinib until treatment failure or undue toxicity. Outcomes analyzed included clinical response, survival, and adverse events (AEs). Results: Reasons for enrollment were disease progression (57.6%), CT intolerance (22.2%), significant comorbidity (21.7%), and CT refusal (21%). Predominant (66%) histology was adenocarcinoma, 16.2% with bronchioloalveolar subtype: 186 pts (93.9%) had stage III/IV disease, 3 (1.5%) were stage I/II, and 9 (4.5%) had no staging data recorded. Fifty-six (28.3%) patients had ECOG performance status (PS) ≥2. Although PS was not recorded for 69 (34.8%) pts, at enrollment 60% were nonambulatory, 15.2% required oxygen, and 4% were in a hospice. Median survival was 6 months (95% CI, 5–8 mo); estimated 1-year survival rate was 29.7% (95% CI, 22.1–37.3%). In 142 (72.2%) pts with ≥1 imaging study postenrollment, complete, partial, and stable response rates were 0.7%, 5.6%, and 40.6%, respectively. Most common AEs were diarrhea (31.3%), rash (31.3%), asthenia (15.7%), anorexia (11.6%), and nausea (11.1%). Mean treatment duration was 4.7 months (range 0.1–26 mo). Post-EAP treatment data were available for 157 (79.3%) pts: 36 (22.9%) of this group went on to further treatment, 25 received CT, and 11 received radiation therapy. Conclusions: Oral gefitinib was well tolerated and effective in this unselected population of chemo-naive pts with NSCLC who were unsuitable for or refused CT. Median and 1-year survival were significantly better than with best supportive care alone and similar to CT, with substantially less toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Genentech, Ligand Amgen, AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, Genentech, Merck, Pfizer Amgen, AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, Genentech, Genta, Ligand, Pfizer AstraZeneca Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly
Doctors in Scotland must change working patterns
Authors: Bryan Christie
Journal: BMJ (2002)

Changes are needed in the way doctors work if the ever rising demand for health care is to be met, a review of future medical workforce requirements in Scotland has concluded.

It says that more doctors will be needed in Scotland, but they will have to work differently. The report says that more effective partnership working is needed in primary care, together with a redesign of hospital services—including a separation of “cold units,” specialising in elective work, and “hot units,” handling acute and emergency cases.

The report of the review, chaired by Professor John Temple, president of the Royal College of Surgeons of Edinburgh, says: “A solution that relies on securing yet more doctors to work much as they have done in the past looks increasingly untenable. Redesign of the delivery of services is in our view inevitable.”

It makes 37 recommendations, including a number of practical measures designed to improve medical recruitment and retention. These include promoting medical careers to school students; special packages to attract doctors to rural areas; arrangements to accommodate the needs of doctors at the end of their careers to prevent them retiring early; and measures to make medicine a more attractive career option.
Abstract 806: Prognostic Value of Multimarker Approach Using Cardiac Troponin T, N-Terminal Pro-B-Type Natriuretic Peptide, and Cystatin C in Patients Hospitalized for Worsening Chronic Heart Failure
Authors: Hiroyuki Naruse, Junnichi Ishii, Shino Kan, Masanori Okumura, Tadashi Nakano, Yoshihisa Mori, Shigeru Matsui, Masanori Nomura, Hitoshi Hishida, Yukio Ozaki
Journal: Circulation (2008)
Abstract 1378: NFkb Blockade Attenuate Cytokines And Oxidative Stress In The Paraventricular Nucleus And Decreases Neurohumoral Excitation In Spontaneously Hypertensive Rats
Authors: Nithya Mariappan, Carrie Elks, Masudul Haque, Philip J Ebnezer, Elizabeth McIIwain, Edmund K Kerut, Joseph Francis
Journal: Circulation (2007)

The transcriptional factor, nuclear factor kappa B (NFkB) plays an important role in the regulation of cytokines. Among the cytokines, tumor necrosis factor-alpha (TNF) plays an important role in cardiovascular pathophysiology. This study was done to determine whether TNF-α blockade with etanercept (ETN) or NFkB blockade with dithiol pyrolidine thiocarbamate (PDTC) attenuate oxidative stress in the paraventricular nucleus (PVN) and contribute to neurohumoral excitation in spontaneously hypertensive rats. Method: Male 20 week old SHR rats were treated with ETN (1 mg/kg BW, sc) or PDTC (100mg/kg BW, ip) for 5 week period. Left ventricular function was measured at baseline (20 weeks) and at 25 weeks using echocardiography. Blood pressure was measured at weekly intervals throughout the study. At the end of the protocol rats were sacrificed the PVN was microdissected for the measurement of cytokines, oxidative stress markers using real time PCR (fold increase compared to WKY controls) and by immunohistochemistry. Superoxide, total reactive oxygen species and peroxynitrite were measured in the PVN and LV using electron paramagnetic resonance. Plasma norepinephrine and epinephrine an indicator of neurohumoral excitation was measured using HPLC-EC. Results: PVN data are tabulated. SHR animals had increased expression of protein and mRNA for cytokines and oxidative stress markers in the PVN and LV with increased MAP and cardiac hypertrophy when compared to WKY rats. Treatment with ETN and PDTC attenuated these increases with PDTC showing marked effect than ETN on hypertrophy and blood pressure responses. Conclusion: These findings suggest that cytokine activation in the PVN contributes to increased oxidative stress and neurohumoral excitation in hypertension.
Clinical Pharmacokinetic (PK) and Safety (Immunogenicity) of Rituximab Biosimilar RTXM83 in Combination with Chemotherapy CHOP in Patients with Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Amalia Florez, Thiago Di Matteo, Gloria Fresnillo, Consuelo Tudela, Mauricio Seigelchifer, Esteban Corley, Analia Pesce, Cedric Bes, Susana Millan
Journal: Blood (2014)
Accrual to clinical trials at selected comprehensive cancer centers
Authors: D. M. Dilts, A. B. Sandler, S. Cheng, J. Crites, L. Ferranti, A. Wu, M. A. Bookman, J. P. Thomas, J. Ostroff
Journal: Journal of Clinical Oncology (2008)

6543 Background: To examine the accrual rates for all phases clinical trials opened at four selected comprehensive cancer centers (CCCs). Methods: Accrual data for the date ranges was collected for all non-pediatric clinical trials at the following CCCs: Fox-Chase Cancer Center (1/2000–4/2007), Lineberger Comprehensive Cancer Center at the University of North Carolina (1/2000–12/2005), The Ohio State Comprehensive Cancer Center (1/2000–4/2007) and the Vanderbilt-Ingram Comprehensive Cancer Center (1/2001–7/2005). Data were collected on all studies, regardless of phase, at these institutions. Results: The mean number of clinical trials that resulted in 0 accruals was 28.6% (257 of 898 trials, range: 20.6% - 34.4%) for the four selected cancer centers. The mean number of studies with less than 5 accruals was 59.4% (534 of 898 trials, range: 53.6% - 68.0%). These data exclude all pediatric trials but include trials for rare cancers, which may explain some of the low accruals. Conclusion: Review of accrual data from four selected CCCs reveals that a high percentage of clinical trials accrue far fewer patients than would be expected. Assuming that some percentage may involve studies in rare cancers having nearly 60% of studies accrue less than 5 patients is higher than one would expect. With the current environment of reduced funding for clinical trials, it is critical that more emphasis be directed toward identifying vital characteristics of study accrual performance. We are currently collecting additional data to investigate if there are significant difference in accrual rates based on funding source, phase or time to open a study. These results will be available by the time of the meeting. Accrual Per Trial for Selected Comprehensive Cancer Centers Accrual per Trial CCC 1 CCC 2 CCC 3 CCC 4 Total N 148 323 104 323 898 0 20.9% 26.9% 26.9% 34.4% 28.6% 1 to 4 33.0% 32.3% 30.3% 31.3% 30.8% 5 to 10 19.3% 16.1% 22.7% 18.0% 18.6% 11 to 15 11.0% 7.3% 8.4% 4.3% 7.7% 16 to 20 3.7% 3.7% 3.4% 5.3% 4.1% >20 12.4% 15.0% 7.6% 6.8% 10.1% Excludes pediatric trials No significant financial relationships to disclose.
Abstract 964: Effect of Volume Overload on Left Ventricular Torsion and Extra Cellular Matrix
Authors: Hosakote M Nagaraj, Thomas S Denney, Steven G Lloyd, David Calhoun, Inmaculada Aban, Cecilia Corros, Gilbert J Zoghbi, Gilbert J Perry, Louis J Dell’Italia, Himanshu Gupta
Journal: Circulation (2007)

Background: Muscle fibers are arranged in a spiral network and are connected by extracellular matrix (ECM). LV torsion is increased in the pressure overloaded heart where there is an increase in ECM. However, torsion and its relation to ECM have not been systematically studied in the volume overloaded heart. Hypothesis: The volume overloaded heart has a decrease in LV torsion due a loss of ECM. Methods: Primary mitral regurgitation (MR) (n=29), resistant hypertension (HTN) (n=77) and normal volunteers (NL) (n±37) were studied. Comprehensive cardiac magnetic resonance imaging (MRI) with tissue tagging was performed and analyzed using three-dimensional data set. Torsion was computed by fitting a B-spline deformation model in prolate-spheroidal coordinates to the tag line data. A subset of MR subjects had LV collagen assessed by picric acid Sirius red from biopsy samples taken at the time of surgery. Results: LV ejection fraction was 65% in MR and 70% in HTN. MR demonstrated eccentric remodeling and HTN demonstrated concentric remodeling. HTN had significantly higher torsion angle and systolic twist compared to NL and MR. This was associated with a simultaneous decrease in longitudinal strain. In contrast, MR patients had similar torsion indices, circumferential and longitudinal strains compared to NL. LV biopsy in MR demonstrated a decrease in interstitial collagen compared to NL. Conclusions: As opposed to the pure volume overloaded heart, LV torsional forces are increased in the pressure overloaded heart. This difference may be related to a rearrangement of the laminar structure due to a differential effect on ECM in the volume overloaded versus the pressure overloaded heart.