tbuckley/cabot-search huggingface dataset:
The association between chronic airflow obstruction and poverty in 12 sites of the multinational BOLD study
Authors: John Townend, Cosetta Minelli, Kevin Mortimer, Daniel O. Obaseki, Mohammed Al Ghobain, Hamid Cherkaski, Myriam Denguezli, Kirthi Gunesekera, Hasan Hafizi, Parvaiz A. Koul, Li C. Loh, Chakib Nejjari, Jaymini Patel, Talant Sooronbayev, Sonia A. Buist, Peter G.J. Burney
Journal: European Respiratory Journal (2017)

Poverty is strongly associated with mortality from COPD, but little is known of its relation to airflow obstruction.In a cross-sectional study of adults aged ≥40 years from 12 sites (N=9255), participating in the Burden of Obstructive Lung Disease (BOLD) study, poverty was evaluated using a wealth score (0-10) based on household assets. Obstruction, measured as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (%) after administration of 200 μg salbutamol, and prevalence of FEV1/FVC<lower limit of normal were tested for association with poverty for each site, and the results were combined by meta-analysis.Mean wealth scores ranged from 4 in Blantyre (Malawi) and Kashmir (India) to 10 in Riyadh (Saudi Arabia), and the prevalence of obstruction, from 16% in Kashmir to 3% in Riyadh and Penang (Malaysia). Following adjustments for age and sex, FEV1/FVC increased by 0.36% (absolute change) (95%CI: 0.22, 0.49; p<0.001) per unit increase in wealth score. Adjustments for other confounders reduced this effect to 0.23% (0.11, 0.34), but even this value remained highly significant (p<0.001). Results were consistent across sites (I2=1%; phet=0.44). Mean wealth scores explained 38% of the variation in mean FEV1/FVC between sites (r2=0.385, p=0.031).Airflow obstruction is consistently associated with poverty at individual and community levels across several countries.
Right Ventricular Function in Heart Failure With Preserved Ejection Fraction
Authors: Selma F. Mohammed, Imad Hussain, Omar F. AbouEzzeddine, Hiroyuki Takahama, Susan H. Kwon, Paul Forfia, Véronique L. Roger, Margaret M. Redfield
Journal: Circulation (2014)

Background— The prevalence and clinical significance of right ventricular (RV) systolic dysfunction (RVD) in patients with heart failure and preserved ejection fraction (HFpEF) are not well characterized. Methods and Results— Consecutive, prospectively identified HFpEF (Framingham HF criteria, ejection fraction ≥50%) patients (n=562) from Olmsted County, Minnesota, underwent echocardiography at HF diagnosis and follow-up for cause-specific mortality and HF hospitalization. RV function was categorized by tertiles of tricuspid annular plane systolic excursion and by semiquantitative (normal, mild RVD, or moderate to severe RVD) 2-dimensional assessment. Whether RVD was defined by semiquantitative assessment or tricuspid annular plane systolic excursion ≤15 mm, HFpEF patients with RVD were more likely to have atrial fibrillation, pacemakers, and chronic diuretic therapy. At echocardiography, patients with RVD had slightly lower left ventricular ejection fraction, worse diastolic dysfunction, lower blood pressure and cardiac output, higher pulmonary artery systolic pressure, and more severe RV enlargement and tricuspid valve regurgitation. After adjustment for age, sex, pulmonary artery systolic pressure, and comorbidities, the presence of any RVD by semiquantitative assessment was associated with higher all-cause (hazard ratio=1.35; 95% confidence interval, 1.03–1.77; P =0.03) and cardiovascular (hazard ratio=1.85; 95% confidence interval, 1.20–2.80; P =0.006) mortality and higher first (hazard ratio=1.99; 95% confidence interval, 1.35–2.90; P =0.0006) and multiple (hazard ratio=1.81; 95% confidence interval, 1.18–2.78; P =0.007) HF hospitalization rates. RVD defined by tricuspid annular plane systolic excursion values showed similar but weaker associations with mortality and HF hospitalizations. Conclusions— In the community, RVD is common in HFpEF patients, is associated with clinical and echocardiographic evidence of more advanced HF, and is predictive of poorer outcomes.
Is adding rituximab to CHOP regimen beneficial to patients with extranodal diffuse large B-cell lymphoma? A retrospective study.
Authors: Agnieszka Badora, Sebastian Giebel, Ewa Chmielowska, Maciej Studzinski, Elzbieta Nowara
Journal: Journal of Clinical Oncology (2014)

e19511 Background: Adding rituximab to CHOP regimen led to significant improvement in diffuse large B-cell lymphoma (DLBCL) treatment outcomes, but its role in case of extranodal DLBCL remains controversial. The aim of the study was to evaluate the efficacy of immunochemotherapy among patients with extranodal DLBCL. Methods: We conducted a retrospective analysis of medical documentation of 230 patients treated in Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch and Franciszek Łukaszczyk Memorial Cancer Center in Bydgoszcz between 2004 and 2011. Inclusion criteria were: newly diagnosed DLBCL CD20(+), patient age above 18 years and first-line treatment with R-CHOP (n=178) or CHOP (n=52) regimen. Patients suffering from primary central nervous system lymphoma, primary mediastinal B-cell lymphoma or with incomplete documentation were excluded. Patient’s characteristics and therapeutic outcomes were compared between group with and without extranodal involvement. Primary endpoints were OS, PFS and EFS. Results: Median time of observation was 70,4 months. The effect of adding rituximab to CHOP was showed separately for patients with (n=125) and without (n=105) extranodal localization of DLBCL. For patients with only nodal presentation the probabilities of OS, PFS and EFS were 79,4 ± 6%, 85,9 ± 6% and 69 ± 6,3% after R-CHOP compared with 43,8 ± 11% (p=0,001), 34,2 ± 13% (p=0,0003) and 41 ± 11% (p=0,002) after CHOP. For patients with extranodal involvement the results were comparable irrespective of the addition of rituximab. The probability of OS was 83,3 ± 4% after R-CHOP vs. 76 ± 8,5% after CHOP (p=0,51). PFS was 89,2 ± 7% vs. 81,9 ± 9% respectively (p=0,16), while EFS was 66,6 ± 5% vs. 57,8 ± 9,7% respectively (p=0,45). The differences remained insignificant in a multivariate model adjusted to IPI. Conclusions: Our analysis did not provide evidence of the beneficial effects of adding rituximab to CHOP regimen on treatment outcome in patients with extranodal DLBCL.
Abstract P157: Ethnic Differences In the Association Between Inflammatory Markers and Cytokines With Coronary Artery Calcium in Postmenopausal Women
Authors: Maria Rosario G Araneta, Christina L Wassel, Gail A Laughlin, Matthew A Allison, Elizabeth Barrett-Connor
Journal: Circulation (2012)

Objective: We assessed the association between TNF-a, IL-6, leptin, and adiponectin with coronary artery calcium (CAC) in postmenopausal women without known cardiovascular disease. Methods: Participants were 192 Caucasian (C), 178 Filipina (F) and 181 African-American (AA) with measures of CVD risk factors, inflammatory markers and cytokines in 1995-99 and CAC in 2000-02. Age adjusted geometric means are presented. Results: Caucasians were significantly older, while AA had larger BMI (C:26.0, F: 25.5, AA: 29.7 kg/m 2 , p&lt;0.001) but lower triglycerides (C:132, F: 153, AA: 92 mg/dl, p&lt;0.001). Filipinas had elevated type 2 diabetes (T2DM) (C: 5.7, F: 32.6, AA: 12.2%, p&lt;0.001) and hypertension (HTN) prevalence (C: 45.3, F: 66.3, AA: 46.4%, p&lt;0.001), statin use (C: 19.3, F: 31.5, AA: 16.6%, p=0.002) and visceral adipose tissue (C: 61.6, F:68.7, AA: 57.6 cm3, p&lt;0.001). Filipinas had significantly lower adiponectin levels than either group, while AA women had higher IL-6 levels than either group, and lower adiponectin than Caucasians. No ethnic differences were observed in leptin, TNF-a levels nor prevalence of CAC score of 100 or higher (p=0.10). Caucasian Filipino African-American Age (yrs) 66.7 64.4 * 61.2 † ‡ TNF-a (pg/ml) 1.02 1.10 1.13 IL-6 (pg/ml) 1.46 1.54 2.08 † ‡ Adiponectin (ug/ml) 12.61 6.15 * ‡ 8.07 † Leptin (ng/ml) 14.24 14.09 15.71 CAC &gt;=100 after 5 yrs 27.1% 29.8% 23.8% p&lt;0.05, * F vs C, † AA vs C, ‡ AA vs F Multivariable regression showed older age (adjusted OR: 1.08, 95% CI:1.15-1.12), log IL-6 (adj OR: 1.69 (1.20 - 2.40)), HTN (adj OR: 1.79 (1.16-2.76)), T2DM (adj OR: 1.85 (1.09- 3.14)), and current statin use (adj OR: 1.99 (1.24-3.18) were independently associated with CAC&gt;=100, after adjusting for VAT, adiponectin, leptin, TNF-a, HDL-c and estrogen use. When stratified by ethnicity, CAC&gt;=100 was associated with older age (adj OR: 1.19 (1.11- 1.27)) and log IL-6 (adj OR: 3.82 (1.71- 8.52)) in Caucasians; older age (adj OR: 1.08 (1.03- 1.14)), log IL-6 (adj OR: 1.79 (1.02- 3.16)), and HTN (adj OR: 3.74 (1.70- 8.257)) among AA; and HTN (adj OR: 2.62 (1.13- 6.04)) and statin use (adj OR: 2.22 (1.08- 4.57)) among Filipinas. Conclusion: IL-6 was associated with CAC&gt;=100 among Caucasian and African-American women, but not among Filipinas. Funding(This research has received full or partial funding support from the American Heart Association, National Center)
The impact of clinically significant discrepancies from primary pathological review of transurethral bladder resection specimens upon repeat review at a tertiary care center.
Authors: Lamont J. Barlow, Edan Shapiro, Jennifer Ahn, Mitchell C. Benson, James M. McKiernan
Journal: Journal of Clinical Oncology (2013)

4552 Background: Internal review of outside pathology slides is a common practice among urologic oncologists at tertiary care facilities, and discrepancies have a potential to directly affect the choice of treatment. While repeat prostate biopsy review has been extensively studied, there is little data available on the impact of repeat reviews of bladder biopsies. The purpose of the current study is to perform a standardized comparison of original and internal pathology reviews of identical bladder specimens to characterize the impact of repeat review on treatment decisions. Methods: Using the Columbia Urologic Oncology Database, a retrospective analysis of 91 consecutive patients who underwent bladder resections at outside institutions from 2008-2012 with secondary referral to a single urologist and internal review at our institution was conducted. Characteristics of both original pathology reports and internal reviews were collected and compared by blinded reviewers. A discrepancy in one of the following characteristics was considered treatment-altering: presence of muscularis in specimen or tumor involvement in muscularis. Additional clinically-significant discrepancies including presence of secondary histology, carcinoma in situ, lymphovascular invasion, micropapillary features, tumor stage, and overall accumulative discrepancy rate were also analyzed. Results: Median time from original procedure to internal review was 34 days (range: 9-368). 56/91 (62%) patients had at least one of the predefined clinically-significant discrepancies. 27/91 (30%) patients had at least one treatment-altering discrepancy, including 25 with discrepant muscle in specimen and 11 with discrepant muscle invasion. Regarding tumor stage, 8 patients were upstaged, 71 were unchanged, and 12 were downstaged on internal review. Conclusions: Repeat pathologic review of primary bladder specimens at a tertiary care center has the potential to alter clinical care for the majority of patients. Further studies are needed to determine if these discrepancies and the decisions they influence have a significant impact on patient outcomes.
The incidence of testicular cancer in the United States and Europe from 1992 to 2009.
Authors: Manas Nigam, Brisa Aschebrook-Kilfoy, Sergey Shikanov, Kyle A Richards, Scott E. Eggener
Journal: Journal of Clinical Oncology (2014)

1585 Background: Testicular germ cell tumors (TGCTs) are the most commonly diagnosed cancer in men between 15 and 35 years in the United States and in most European populations. The incidence of TGCTs increased in White, Black, and Hispanic men in the U.S. through 2003. We sought to determine current trends in TGCT incidence in the U.S. and Europe. Methods: TGCT incidence data covering the U.S. and European populations were extracted from the Surveillance, Epidemiology and End Results-13 registry and the EUREG database, respectively. Age-standardized incidence rates (ASIRs) were derived from SEER*Stat 8.0.1. Trends were determined using JoinPoint. Results: TGCT incidence among U.S. males over 15 years old increased from 1992 (5.7/100,000) to 2009 (6.8) with a significant annual percentage change (APC) (1.1%, p<0.001). TGCT ASIRs were highest in White men (1992: 7.5/100,000; 2009: 8.6/1000) followed by Hispanic men (1992: 4.0; 2009: 6.3) and lowest among Asian (1992: 2.0/100,000; 2009: 2.8) and Black men (1992: 0.7; 2009: 1.7). Significantly increasing ASIRs were observed in White men (APC: 1.2%, p<0.001) and most prominently in Hispanic men, especially from 2002-2009 (APC: 5.6%, p<0.01). Significant increases were observed for localized (APC: 1.2%, p<0.001) and metastatic TGCTs (APC: 1.4%, p<0.01). Incidence of testicular cancer increased in 15 of 19 (79%) European countries analysed (p < 0.05). Conclusions: Between 1992 and 2009, testicular cancer incidence in the U.S. continued to increase, notably among Hispanic men, and testicular cancer incidence increased in 79% of European countries analyzed. Incidence rates for TGCTs among U.S. men, SEER-13, 1992-2009. All GCTs Age-adjusted incidence rate (per 100,000) Annual percentage change (APC) Number of cases 1992 2009 All races 18,037 5.7 6.8 1.1* Non-Hispanic white 13,454 7.5 8.6 1.2* Non-Hispanic black 419 0.7 1.7 1.4 Hispanic 3,052 4 6.3 0.7 (1992-2002)a 5.6* (2002-2009) Other 1,112 2.2 4.4 2.9* Age at diagnosis 15-26 years 4,288 6.2 8.6 2.5* 27-32 years 4,202 11.3 13.8 1.0* 33-39 years 4,461 10.0 9.9 0.1 40+ years 5,086 3.3 3.9 0.8* * Significant at a 0.05 confidence level. a JoinPoint can produce different APCs for different year intervals.
A Matched-Pair Analysis of EPOCH Versus CHOP As Frontline Therapy for Nodal Peripheral T-Cell Lymphoma, Excluding ALK-Positive Anaplastic T-Cell Lymphoma: A Multicenter Experience in Thailand
Authors: Lalita Norasetthada, Weerasak Nawarawong, Udomsak Bunworasate, Kitsada Wudhikarn, Arnuparp Lekhakula, Jakrawadee Julamanee, Tontanai Numbenjapon, Kannadit Prayongratana, Chittima Sirijerachai, Kanchana Chansung, Nisa Makruasi, Somchai Wongkhantee, Pannee Praditsuktavorn, Tanin Intragumtornchai
Journal: Blood (2016)
Book: A Life Course Approach to Women's Health
Authors: T. J Clifford
Journal: BMJ (2003)

Eds Diana Kuh Rebecca Hardy Oxford University Press £37.50, pp 419 ISBN 0 19 263289 2 Rating ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> ![Graphic][5]</img> As a paediatric epidemiologist, I believe—and hope—that the life course approach will shape health and healthcare research over the next century. As Diana Kuh and Rebecca Hardy make clear, we have made great progress with the health of many of the world's populations. However, much work remains to be done, especially among traditionally understudied groups such as women and children. The life course approach is based on the belief that “various biological … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif [5]: /embed/inline-graphic-5.gif
Abstract 356: Scl Represses Cardiogenesis via Distant Enhancers during Hemogenic Endothelium Specification
Authors: Tonis Org, Dan Duan, Roberto Ferrari, Amelie Montel-Hagen, Ben Van Handel, Rajkumar Sasidharan, Stuart H Orkin, Siavash Kurdistani, Hanna K Mikkola
Journal: Circulation Research (2013)

Understanding the mechanisms directing mesoderm specification holds a great potential to advance the development of cell-based therapies for cardiovascular and blood disorders. The bHLH transcription factor Scl is known as the master regulator of the hematopoietic fate. We recently discovered that, in addition to its critical function in promoting the establishment of hemogenic endothelium during hematopoietic stem/progenitor cell (HS/PC) development, Scl is also required to repress cardiomyogenesis in endothelium in hematopoietic tissues and endocardium in the heart. However, the mechanisms for the cardiac repression have remained unknown. Using ChIP-sequencing and microarray analysis of Flk+ mesoderm differentiated from mouse ES cells, we show that Scl both directly activates a broad gene regulatory network required for hemogenic endothelium and HS/PC development (e.g. Runx1, cMyb, Lyl1, Mef2C, Sox7 etc.), and directly represses transcriptional regulators required for cardiogenesis (e.g. Gata4, Gata6, Myocd, etc.) and mesoderm development (Eomes, Mixl1, Etv2, etc.). Repression of cardiac and mesodermal programs occurs during a short developmental window through Scl binding to distant enhancers, while binding to hematopoietic regulators extends throughout HS/PC and red blood cell development and encompasses both distant and proximal binding sites. We also discovered that, surprisingly, Scl complex partners Gata 1 and 2 are dispensable for hematopoietic vs. cardiac specification and Scl binding to majority of its target genes. Nevertheless, Gata factors co-operate with Scl to activate selected transcription factors that facilitate HS/PC emergence from hemogenic endothelium. These results denote Scl as a true master regulator of hematopoietic vs. cardiac fate choice and suggest a mechanism by which lineage-specific bHLH factors direct the divergence of competing fates.
Abstract 95: Pharmacological Characterization of Adenosine Effects on Spontaneously Beating Human-IPSC-Derived Cardiomyocytes
Authors: John P Imredy, Bharathi Balasubramanian, Edward V Lis, Armando Lagrutta, Frederick Sannajust
Journal: Circulation Research (2015)

Purified human-Induced Pluripotent Stem Cell-derived cardiomyocytes (hIPSC-CMs: iCells®, Cellular Dynamics) form electrically coupled, spontaneously beating cell monolayers (syncytia) upon plating and continuous culture. In this study, we investigate the pharmacology of the hIPSC-CM adenosine (ADO) response via the use of selective A1 and A2A-receptor antagonists and equilibrative nucleoside transporter type-1 (ENT1) inhibitors. After a 14-day culture in 96-well impedance electrode-plates (ACEA Biosciences), the spontaneous iCell beating rates are highly stable from well to well, with a mean beat period of 1.7 sec at 37°C, and a coefficient of variation (CV) &lt; 1% . Extracellularly applied ADO inhibits the spontaneous beating rate of iCells with an IC 50 = 2.2 μM, and a saturation value of near 50% inhibition. ADO also destabilizes the beat period (CV EC 50 = 1.2 μM) with a maximum CV of 20% at saturating ADO concentrations. The ADO IC 50 is shifted to 248 μM upon pre-incubation of the iCells with 1 μM of an A1-selective antagonist DPCPX (A1 K i =3.9 nM), but not the A2A-selective antagonist ZM241385 (A2A K i =1nM). The duration of the depressive effect of ADO on beating rate is transient, even at super-saturating ADO concentrations, and depends on the well ADO concentration. The ENT1 inhibitor Draflazine (ENT1 pK i =9.5) pre-applied at 0.1 μM increases ADO sensitivity by 4-fold one hour after ADO application. Moreover, at any given ADO concentration, the duration of beating rate depression can be prolonged in a concentration-dependent manner by ENT1 inhibitors, with the prolongation-response curve nearly matching the ENT1 IC 50 s for tested ENT1 inhibitors (Draflazine, NBTI, Dilazep, and Dipyridamole). These findings suggest that the pool of ADO in the test well is cleared by uptake via endogenous ENT1 and support the role of equilibrative ADO uptake in limiting the duration of action of ADO on A1 receptors in cardiomyocytes. We are extending our investigation to the downstream target of A1 receptor activity, and the putative role of IK ACH/ADO as the underlying mechanism of beat rate slowing and irregularity. In conclusion, the hIPSC-CM model provides a useful model for investigation of ADO pharmacology of the heart.
Understanding and Improving Recruitment to Randomised Controlled Trials: Qualitative Research Approaches
Authors: Daisy Elliott, Samantha Husbands, Freddie C. Hamdy, Lars Holmberg, Jenny L. Donovan
Journal: European Urology (2017)

The importance of evidence from randomised trials is now widely recognised, although recruitment is often difficult. Qualitative research has shown promise in identifying the key barriers to recruitment, and interventions have been developed to reduce organisational difficulties and support clinicians undertaking recruitment.This article provides an introduction to qualitative research techniques and explains how this approach can be used to understand-and subsequently improve-recruitment and informed consent within a range of clinical trials.A literature search was performed using Medline, Embase, and CINAHL. All studies with qualitative research methods that focused on the recruitment activity of clinicians were included in the review.The majority of studies reported that organisational difficulties and lack of time for clinical staff were key barriers to recruitment. However, a synthesis of qualitative studies highlighted the intellectual and emotional challenges that arise when combining research with clinical roles, particularly in relation to equipoise and patient eligibility. To support recruiters to become more comfortable with the design and principles of randomised controlled trials, interventions have been developed, including the QuinteT Recruitment Intervention, which comprises in-depth investigation of recruitment obstacles in real time, followed by implementation of tailored strategies to address these challenges as the trial proceeds.Qualitative research can provide important insights into the complexities of recruitment to trials and inform the development of interventions, and provide support and training initiatives as required. Investigators should consider implementing such methods in trials expected to be challenging or recruiting below target.Qualitative research is a term used to describe a range of methods that can be implemented to understand participants' perspectives and behaviours. Data are gathered from interviews, focus groups, or observations. In this review, we demonstrate how this approach can be used to understand-and improve-recruitment to clinical trials. Taken together, our review suggests that healthcare professionals can find recruiting to trials challenging and require support with this process.