tbuckley/cabot-search huggingface dataset:
Long-term ototoxicity in testicular cancer survivors (TCSs) after cisplatin-based chemotherapy: associations with Gluthatione-S-Transferase (GST)-T1, -P1, and -M1 genotypes
Authors: J. Oldenburg, S. M. Kraggerud, M. Berg, A. A. Dahl, B. Engdahl, V. N. Kristensen, R. A. Lothe, S. D. Fossa
Journal: Journal of Clinical Oncology (2005)

4575 Background: Cisplatin-induced ototoxicity shows considerable inter-individual variations. Genetic variations in enzymes involved in detoxification of cisplatin could contribute to the observed toxicity variation. We aimed to investigate potential associations among polymorphisms in GST-T1, -P1, and -M1, their combinations, and ototoxicity in TCSs. Methods: Audiograms were obtained from 174 Norwegian TCSs at a median of 12 years (range: 4–20) after primary treatment. All TCSs had cumulatively received ≥600mg cisplatin (median 800mg, range: 600-1950). “Impaired hearing” was scored when decibel values were above the 75 percentile at 4000 Hertz of age-matched Norwegian men. For all TCSs, DNA was extracted from peripheral blood samples and submitted to genetic analyses. Known functional polymorphisms (positive/nulltype) in GSTT1 and GSTM1, and (codon 105 A/G (Ile/Val)) in GSTP1 were analyzed by multiplex PCR, followed by restriction enzyme cutting, and separated by gel electrophoresis. Different genotypes and their combinations were tested against ototoxicity. Results: Five of the 12 possible GST genotype combinations comprised more than 10 TCSs, and these were submitted to a χ2-test versus “Impaired hearing”. Two significant associations were found: χ2(Pattern1=GST-T1-positive,-P1,-AA,-M1- positive): p=0.045; OR 0.4, (95%CI 0.2–1.0) χ2(Pattern2=GST-T1- positive,-P1,-AA,-M1-nulltype): p=0.016; OR 2.7, (95%CI 1.2–6.1) No significant associations were found for the single genotypes. Conclusion: The prevalence of impaired hearing was lower in TCSs with Pattern 1 than in those without this pattern (19% vs. 37%). The opposite association was found for Pattern 2 (54% vs. 30%). Genetic variations in detoxifying enzymes may play a role in the development of cisplatin-induced ototoxicity. No significant financial relationships to disclose.
Abstract 4231: Impact of Stress Echocardiography on Patient Outcome: An Effective Gatekeeper for Coronary Angiography
Authors: Siu-Sun Yao, Sripal Bangalore, Ajay Shah, Jorge Silva-Encisco, Farooq A Chaudhry
Journal: Circulation (2008)

Stress echocardiography is an established technique for the diagnosis, risk stratification and prognosis of patients with known or suspected coronary artery disease. The impact of stress echo in patient selection for coronary angiography is unclear. We assessed 3121 patients (60 ± 13 years, 48% male) undergoing stress echo (41% treadmill, 59% dobutamine). Follow-up (mean 2.8 ± 1.1 years) for subsequent angiography (&lt;&lt;26&gt;2 months), confirmed non-fatal myocardial infarction (n = 76) and cardiac death (n = 83) were identified. Stress echo was abnormal in 34% and normal in 66%. Peak wall motion score index (pWMSI) effectively risk stratified patients into low-normal stress echo (0.8%/year), intermediate (2.6%/year) and high (5.5%/year) risk groups (p &lt; 0.0001). Early coronary angiography was performed in only 128 patients (1.7%) with normal stress echo and increased with worsening stress echo - 226 patients (22.9%) with pWMSI=1.1–1.7 and 191 patients (41.9%) with pWMSI&gt;1.7. Multivariate logistic regression analysis identified pWMSI as the strongest predictor of future angiography (relative risk 2.04, 95% confidence interval 1.67–2.5, p&lt;0.0001) and cardiac events (relative risk 2.45, 95% confidence interval 2.09 –2.88, p&lt;0.0001). Stress echo is an effective gatekeeper for coronary angiography. The overall mortality rate for patients with normal stress echo was 0.8%/year. Only 1.7% of patients with normal stress echo were referred for early angiography.
Abstract 5577: Short-Term Outcomes of STEMI and NSTEMI in Patients with Chronic Kidney Disease: A Report from the National Cardiovascular Data ACTION Registry
Authors: Caroline S Fox, Paul Muntner, Anita Y Chen, Karen P Alexander, Matthew T Roe, Jorge F Saucedo, Stephen D Wiviott
Journal: Circulation (2008)

Chronic kidney disease (CKD) is a risk factor for myocardial infarction (MI) and death. However, the relationship between severity of CKD and contemporary hospital-based management and outcomes across the spectrum of MI (STEMI and NSTEMI) has not been well-documented. The study population was drawn from the ACTION Registry, a nation-wide sample of STEMI (n=19,481) and NSTEMI (n=30,462) patients admitted to 274 hospitals in the United States between January 1 and December 31, 2007. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) equation and categorized as ≥60, 30 to &lt;60, 15 to &lt;30 and eGFR&lt;15 mL/min/1.73m 2 or dialysis. Use of acute (first 24 hours) therapies and early (first 48 hours) cardiac catheterization as well as in-hospital major bleeds, and death were compared across CKD stages in models adjusted for demographics, CVD history and prior procedures, and risk factors. Overall, 30.5% and 42.9% of patients with STEMI and NSTEMI, respectively, had CKD Stage III or greater (eGFR&lt;60 ml/min/1.73m 2 or dialysis). Regardless of MI type, patients with CKD were less likely to receive acute evidence-based therapies including aspirin, beta-blockers or clopidogrel or to undergo early invasive care and were more likely to experience a major bleed or death (Table ). There were 1030 deaths among those presenting with STEMI, and 1223 among those with NSTEMI. There was a greater relative increase in death for patients with STEMI with advancing CKD stage than was seen in NSTEMI (P interaction &lt;0.0001 for each stage). A large proportion of patients presenting with STEMI or NSTEMI have CKD. Further efforts to address treatment gaps in the management of MI in the presence of CKD are needed to improve outcomes in this high-risk population. Table- Multivariable adjusted odds ratios and 95% confidence intervals of outcomes based on CKD stage
Abstract 14169: Understanding Childhood Obesity in America: Linkages Between Household Income, Community Resources, and Children's Behaviors
Authors: Taylor F Eagle, Anne Sheetz, Roopa Gurm, Alan C Woodward, Eva Kline-Rogers, Robert Leibowitz, Jean DuRussel-Weston, LaVaughn Palma-Davis, Susan Aaronson, Catherine M Fitzgerald, Lindsey R Mitchell, Bruce Rogers, Patricia Bruenger, Katherine A Skala, Caren Goldberg, Elizabeth A Jackson, Steve R Erickson, Kim A Eagle
Journal: Circulation (2011)

Background Childhood obesity is our nation's most pressing health problem. Understanding its causes is critical to the creation of strategies to improve our children's health. Study Questions What ...
Abstract 14572: Poor Understanding and Compliance Among AF Patients on Warfarin Who Use Vitamin Supplements
Authors: Megan B Smith, Nedra Christensen, Jennifer Strohecker, Jeffrey L Anderson, Benjamin D Horne, John D Day, Peter Weiss, Brian G Crandall, Jeffrey S Osborn, Brent Muhlestein, Donald L Lappe, Heidi Moss, Jessica Oliver, Krista Viau, Thomas J Bunch
Journal: Circulation (2011)

Background: Vitamin supplements can interact with warfarin, exposing patients that use them to risk of thromboembolism and/or bleeding. It is unknown if patients that use vitamin supplements have m...
Patients and medical power
Authors: R. Dingwall, J Calinas-Correia, D. Nestel
Journal: BMJ (2001)

Editor—Canter raises important points about the problematic nature of power and the idea that it can simply be shifted from one party to another, particularly given the asymmetries of knowledge and skill that are structurally inherent in professional-client relationships.1 However, his challenge to Alan Milburn, the health minister, stops short of the crucial question about whether a national health service should seek to achieve a “decisive shift of power in favour of the patient.” The potential implication of this statement—that doctors should simply give patients what they want—is fundamentally incompatible with the ethics of taxation.

As Canter's analysis hints but does not explicate, Milburn's statement implies that doctors should prescribe unnecessary antibiotics, carry out unnecessary surgery, and make available untested treatments—all in the name of patient power. Where does this leave the simultaneous investment in the National Institute for Clinical Excellence, evidence based medicine, and medicines management? More to the point, where does it leave the NHS on the morality of its funding from tax levies?

In an insurance based system I can choose to pay for the level of access that I want. If I want a consumer driven system that gives me absolute freedom of choice then I can pay for it, at least to the extent that I can afford the premiums or can persuade others to join me in a risk pool where we each agree to fund the others' unlimited choices.

In a tax funded system we must consider the ethics of compulsorily levying all taxpaying citizens and whether this can ever be justified beyond the extent of providing demonstrably efficient and effective care to those citizens. Doctors are the agents of restraint on behalf of taxpayers.

As a patient, I may want the NHS to do everything for me that may be of any conceivable benefit or that will, at least, make me feel good about it. As a taxpayer, I do not want to see my income sequestered to indulge the fancies of others when there is a clear medical view that an intervention has no clear and established benefit. It is a politician's duty to manage that conflict and the medical profession's task to produce practical resolutions in individual cases.

Loose talk about shifts in power is just that and should give way to the more sophisticated debate that Canter is seeking to encourage.
Congenital Heart Disease
Authors: J. C. Joyce, S. P. O'Toole
Journal: BMJ (1954)

Congenital heart disease in more than one member of a family, although relatively uncommon, has been reported in the literature on a number of occasions.Abbott (1927) found 11 pairs of brothers and sisters, and Brown (1939) reported six instances.Taussig (1947) has seen four families in which more than one member was affected, and in two of these the condition was transmitted through more than one generation.The purpose of this paper is to report four cases occurring in one sibship.This is exceedingly rare, and, so far as we can ascertain from the literature, has been reported only once previously.That was by Walker and Ellis (1940-1), who described a father and four out of eight children with persistent ductus arteriosus.
Second-line therapy with pemetrexed after gemcitabine failure in patients with unresectable locally advanced or metastatic pancreatic cancer: A multicenter phase II trial
Authors: S. Boeck, K. Weigang-Koehler, M. Fuchs, E. Kettner, D. Quietzsch, J. Trojan, O. Stötzer, E. Mueller, H. Depenbrock, V. Heinemann
Journal: Journal of Clinical Oncology (2006)

4124 Background: There is no established second-line therapy for advanced pancreatic cancer after failure of standard first-line treatment with gemcitabine. In view of the urgent need of such therapy and the observation of clinically meaningful responses with pemetrexed in previously untreated pancreatic cancer, this phase II study evaluated pemetrexed as second-line therapy. Methods: This study was planned to evaluate the efficacy and safety of pemetrexed in 54 patients (pts) with unresectable locally advanced or metastatic pancreatic cancer (stage II-IV), ECOG performance status ≤2 and estimated life expectancy of ≥12 weeks (wks) after failure of first-line gemcitabine single agent or combination therapy. Pemetrexed was started at 500 mg/m 2 q3w (10 min infusion), with vitamin B 12 and folic acid supplementation. Dose escalation by 100 mg/m 2 every other cycle and an unlimited number of cycles were allowed. Primary endpoint was the 3-month survival rate. Results: A total of 189 treatment cycles (median 2, range 1–20) was given to 52 pts (60% male, median age 63 yrs, median time since initial diagnosis 32 wks, 89% stage IV disease). Doses were escalated in 2 pts (4%) and reduced due to toxicity in 9 pts (17%); median dose per cycle was 500 mg/m 2 (range 212–700 mg/m 2 ). The 3-month survival rate was 75% (95% CI 63.2–86.8%). At a median follow-up of 20 wks, the median overall survival estimate was 20 wks, with 9 pts alive including 1 still on pemetrexed. Median TTP was 7 wks (range 1–62 wks). The overall response rate was 3.8% (0 CR, 2 PR); 12 pts (23%) had SD for ≥6 wks, 9 of them for ≥12 wks. CA 19–9 decreased at least once by ≥ 50% in 12 pts (23%). Grade 3/4 hematological toxicity rates per pt were as follows: neutropenia 17.3% (febrile neutopenia: 3.8%), leukopenia 15.4%, thrombopenia 5.8% and anemia 3.8%. Conclusion: Pemetrexed is a feasible option for second-line therapy with mild toxicity and encouraging activity in unresectable locally advanced or metastatic pancreatic cancer after gemcitabine failure. [Table: see text]
Abstract 10321: Association of 25(OH) Vitamin D Levels and All-cause and CVD Mortality in the Women's Health Initiative
Authors: Charles B Eaton, Jennifer Robinson, Lisa W Martin, Lewis Kuller, J. David Curb, Matthew Allison, Linda Van Horn, Anne McTiernan, Simin Liu, JoAnn Manson, Ira Ockene
Journal: Circulation (2010)

Background: Prospective epidemiologic data relating serum levels of 25(OH) Vitamin D to mortality are limited. Objectives: To determine if 25(OH) Vitamin D levels are prospectively and independently associated with cardiovascular disease (CVD) and all-cause mortality in post-menopausal women. Methods: Within the Women's Health Initiative observational study and clinical trial control groups, 1829 post-menopausal women who had baseline serum 25(OH) Vitamin D levels measured were followed for over 10 years for CVD death and all-cause mortality. Using inverse probability weighting to account for non-random selection of the sub-cohort, proportional hazards models were performed evaluating quartiles of season standardized 25(OH) Vitamin D levels adjusting for age, ethnicity, clinical trial indicator, smoking status, history of hypertension, systolic blood pressure, history of treated diabetes, history of CVD, history of fracture on or after age 55, and history of cancer; waist circumference, and weekly alcohol...
P0792 : Baseline factors associated with increased SVR rates in 123 treatment-naïve chronic HCV genotype 1 patients treated with a shortened 12-week simeprevir plus pegylated interferon and ribavirin regimen: a multivariate analysis
Authors: T. Asselah, C. Moreno, C. Sarrazin, M. Gschwantler, G.R. Foster, A. Craxi, P. Buggisch, R. Ryan, O. Lenz, G. Van Dooren, I. Lonjon-Domanec, M. Schlag, M. Buti
Journal: Journal of Hepatology (2015)
Abstract 9970: Combined Clenbuterol and Metoprolol Therapy Improves Cardiac Function and Calcium Handling in a Rodent Model of Heart Failure, but Does Not Prevent Myocardial Atrophy or Enhance Myocyte Recovery Associated with Mechanical Unloading
Authors: Manoraj Navaratnarajah, Carin van Doorn, Urszula Siedlecka, Michael Ibrahim, Adarsh Shah, Ajay Gandhi, Priyanthi Dias, Magdi Yacoub, Cesare Terracciano
Journal: Circulation (2011)

Clenbuterol (CL) a β 2 -AR agonist has been successfully employed alongside β 1 -AR blockade in combination with left ventricular assist devices (LVAD) to prevent myocardial atrophy, and promote myocardial recovery in patients with severe heart failure (HF). CL is known to have beneficial effects on excitation contraction (EC) coupling in HF and during mechanical unloading (MU) in animal models. However, CL-induced cardiac hypertrophy and tachycardia have discouraged its use in clinical HF therapy. We compared the chronic effects (4 wks) of CL (2mg/kg/day) and metoprolol (M) (200mg/kg/day) alone and in combination with MU (heterotopic abdominal transplantation) on heart/cardiomyocyte size, function and cellular EC coupling in a rat model of HF (LAD ligation). CL improved ejection fraction compared to untreated HF group, an effect further augmented by M (EF (%): HF 36.2 ± 2.3, p&lt;0.01 vs CL 40.78 ± 2.1, p&lt;0.001 vs M+CL 44.3 ± 2.3 (all groups n=8). CL caused a rise in heart rate (HR) but, when combined with M, HR was reduced (both groups p&lt;0.01 vs HF). CL caused cardiac hypertrophy whereas combined M+CL did not (heart weight:body weight ratio (g/g x 1000)): HF 3.6 ± 0.28, p&lt; 0.05 vs CL 4.2 ± 0.38, Μ+CL 3.6 ± 0.24, p&gt;0.05 vs HF (all groups n=8). Both groups failed to prevent MU-induced myocyte atrophy, but myocyte size was greater in MU+CL group compared with MU+M+CL (cell volume measured by di-8-ANNEPS staining and confocal microscopy (µm3)): MU+ CL 30025 ± 8562, p&lt;0.001 vs MU + M+CL 18750 ± 7500, (both groups n= 50). Myocyte Ca 2+ cycling was studied using the fluorescent dye Indo-1 AM. Ca 2+ transient amplitude was elevated in M+CL group but was not affected by CL (ratio units): HF 0.14 ± 0.06, p&lt;0.001 vs M+CL 0.19 ± 0.09 (both groups n=26). CL alone and M + CL augmented sarcoplasmic reticulum Ca2 + content equally (ratio units): CL 0.20 ± 0.04, M + CL 0.22 ± 0.06, both groups p&lt;0.01 vs HF, (all groups n=20). MU alone normalised HF cardiomyocyte EC parameters with no additional benefit derived by M+CL therapy. We show that combination of CL and M enhances whole heart function and cellular EC coupling in HF without increase in heart size or HR, but does not affect the consequences of MU on cell size and function. Whether such effects can be exploited in the treatment of HF patients requires further studies.
Abstract 5020: The Association between Different Measures of Blood Pressure and Coronary Artery Calcium in Postmenopausal Women
Authors: Matthew A Allison, JoAnn Manson, Robert Langer, Aaron Aragaki, Sylvia Smoller, Cora Lewis, Asha Thomas, William Lawson, Barbara Cochrane, Judith Hsia, Julie Hunt, Jennifer Robinson
Journal: Circulation (2008)

Background: The aim of this study was to determine the magnitude and significance of the associations between coronary artery calcium (CAC) and different measures of blood pressure among postmenopausal women. Methods: Subjects were a subset of women aged 50 to 59 at baseline in the Women’s Health Initiative (WHI) clinical trial of conjugated equine estrogen (CEE) who underwent a one-time computed tomography (CT) scan of the chest following the end of the trial to determine CAC. At the baseline WHI clinic visit, CEE trial participants provided data on a wide range of factors to include blood pressure measurements which were measured twice with the participant in the seated position using a conventional mercury sphygmomanometer and appropriately sized cuffs. Results: The sample consisted of 1,064 women with a mean age of 55.1 (2.8) years at WHI randomization and 64.8 (2.9) years at CAC ascertainment. The prevalence of a CAC score &gt; 0 was 47%, while the prevalence of a CAC score &gt;= 10 and &gt; 100 was 39 and 19%, respectively. There was a linear association between the log-odds of any CAC and SBP while there was a curvilinear and inverse association with DBP that was independent of CVD risk factors and blood pressure medication status. For any value of diastolic blood pressure, the probability of CAC increased with higher levels of SBP. Conversely, for any given value of SBP, the probability of any CAC decreased with higher levels of DBP. Those with a PP &gt;= 55 mmHg had nearly a two-fold higher odds for having any CAC (Odds Ratio: 1.95, 95% CI: 1.24 – 3.06) while individuals with isolated systolic hypertension (SBP &gt;= 140 and DBP &lt; 90) had a 73% higher odds for CAC (95% CI: 1.03 – 2.90, p = 0.04) independent of other risk factors and blood pressure medication status. There was no significant associations between mean arterial pressure and CAC. Conclusions: In postmenopausal women over the age of 50 years, both SBP and DBP are relevant for determining the risk for coronary artery calcium. Notably, higher levels of pulse pressure and systolic blood pressure were strong determinants of CAC, while diastolic blood pressure was inversely related. Consequently, isolated systolic hypertension may be relevant in women. These results may be of clinical relevance for the prevention of coronary artery disease. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Autologous dendritic cell vaccination (DCVAC/PCa) added to docetaxel chemotherapy in a double-blind, randomized phase III trial (VIABLE) in men with advanced (mCRPC) prostate cancer.
Authors: Nicholas J. Vogelzang, Tomasz M. Beer, Jirina Bartunkova, Rostislav Kuklík, Kurt Miller, William K. Oh, Stephane Oudard, Hardev S. Pandha, A. Oliver Sartor, Radek Spisek, Niels Geert Borgstein, Winald R. Gerritsen
Journal: Journal of Clinical Oncology (2015)

TPS5070 Background: Prostate cancer (PCa) is the second most common cancer, and the fifth leading cause of cancer related death among men worldwide. Immunotherapy designed to induce tumor cell specific immune responses capable of destroying tumor cells has emerged as a promising treatment modality in solid malignant tumors. Clinical and preclinical trials have shown that docetaxel chemotherapy can be combined with vaccine without impairing the immune response. Methods: VIABLE is a randomized, double-blind, placebo-controlled, parallel-group, international phase III study to evaluate the efficacy and safety of DCVAC/PCa (active cellular immunotherapy based on dendritic cells) versus placebo in patients with mCRPC eligible for first-line docetaxel chemotherapy. The study was initiated in May 2014 and plans to enroll almost 1200 patients at approximately 300 sites globally. Eligible patients are required to present with metastatic castrate-resistant PCa defined by both presence and progression of the disease, maintenance of a castrate state with serum testosterone level less than 50 ng/dl, ECOG score 0-2, and adequate hematologic, hepatic and renal functions. All patients will receive standard of care docetaxel plus prednisone, and will be randomized 2:1 to DCVAC/PCa or placebo. Patients will be stratified by region (US vs other), previous therapy (enzalutamide and/or abiraterone) and ECOG score (0, 1 vs 2). The primary endpoint is overall survival (OS). Secondary objectives include assessments of safety, radiographic progression free survival, time to PSA progression, time to the first occurrence of skeletal related events (SRE), and quality of life (QoL) assessments based on the FACT-P questionnaire. Clinical trial information: Registration number NCT02111577, EudraCT number 2012-002814-38. Clinical trial information: NCT02111577.
A Large Ribosomal Subunit Protein Abnormality in Diamond-Blackfan Anemia (DBA).
Authors: Jason Farrar, Michelle Nater, Emi Caywood, Michael McDevitt, Jeanne Kowalski, Clifford Takemoto, Connie Talbot, Paul Meltzer, Diane Esposito, Alan Beggs, Hal Schneider, Agnieszka Grabowska, Sarah Ball, Edyta Niewiadomska, Colin Sieff, Adrianna Vlachos, Eva Atsidaftos, Steven Ellis, Jeffrey Lipton, Hanna Gazda, Robert J. Arceci
Journal: Blood (2007)