tbuckley/cabot-search huggingface dataset:
On Gazing Out the Corner Window
Authors: Lawrence J. Hergott
Journal: Annals of Internal Medicine (2016)

Ad Libitum15 March 2016On Gazing Out the Corner WindowLawrence J. Hergott, MDLawrence J. Hergott, MDFrom Center for Bioethics and Humanities, University of Colorado School of Medicine, Denver, Colorado.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-2724 Audio Reading - “On Gazing Out the Corner Window” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "On Gazing Out the Corner Window," by L.J. Hergott. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I got up to fill the birdbath,which I saw needed filling,and now sit gazingat the gardenout our large corner window.The water in the bath is still,and mirrors transfixing autumn colors—the golden ash above,red maples near,a hint of blue and white sky.I sit—in silence, stillness, solitude—without expectation or thought.The water's surface ripples.Leaves quiver.Grey branches sway. Author, Article, and Disclosure InformationAffiliations: From Center for Bioethics and Humanities, University of Colorado School of Medicine, Denver, Colorado.Current Author Address: Lawrence J. Hergott, MD; e-mail, [email protected]net. PreviousarticleNextarticle Advertisement Audio Reading - “On Gazing Out the Corner Window” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "On Gazing Out the Corner Window," by L.J. Hergott. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 15 March 2016Volume 164, Issue 6Page: 448KeywordsMotivation ePublished: 15 March 2016 Issue Published: 15 March 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
ANGI-10GLIOMA-ASSOCIATED MACROPHAGES PROMOTE ENDOTHELIAL CELL DYSFUNCTION
Authors: Julie Metcalf, Kenneth Aldape, Gelareh Zadeh
Journal: Neuro-Oncology (2015)

One of the most prominent features of glioblastoma (GBM) is hyper-vascularization, characterized by abnormal hyper-dilated, distorted, leaky vessels and increased thrombosis. Bone marrow-derived microglia/macrophages are an important host cell population that are actively recruited to the tumour, associate closely with blood vessels, and are thought to provide a supportive role in tumour neo-vascularization. The aim of this study was to investigate the unknown molecular mechanisms of how glioma-associated microglia/macrophages affect endothelial cells to promote neovascularization. Here we examined the effect of conditioned-medium (CM) from M1 (classically activated), M2 (alternatively activated), or glioma neurosphere-associated macrophages (co-cultured) on the expression of angiogenesis genes in human umbilical vein endothelial cells (HUVECs). Strikingly, CM from glioma-associated macrophages produced a substantial upregulation of genes involved in endothelial activation including VCAM-1, ICAM-1, CXCL5, CXCL10, HGF, VEGFC, and SERPINE1 (some up to several thousand-fold increase in expression) in comparison to CM from M1 or M2-polarized macrophages. Gene ontology analysis indicated the possibility of regulation by TNF-α and we therefore examined and confirmed that glioma-associated macrophages show increased secretion of this cytokine. Interestingly, CM from glioma-associated macrophages also led to a downregulation of NOS3 in HUVEC cells, which is known to promote endothelial dysfunction in activated endothelial cells. These findings suggest that glioma-associated macrophages secrete TNF-α, which acts on nearby endothelial cells to promote endothelial activation/ dysfunction. We propose that the pro-inflammatory state of dysfunctional glioma-associated endothelial cells may further increase the recruitment of macrophages through upregulation of adhesion molecules, and promote pro-thrombic properties and vascular leakage that characterize and promote GBM neo-vascularization.
Predicting the histology of renal masses using pre-operative Doppler ultrasonography
Authors: G. V. Raj, A. Iasonos, A. Bach, L. Hann, P. Russo
Journal: Journal of Clinical Oncology (2006)

4598 Background: Traditional imaging techniques cannot differentiate between benign, indolent and malignant renal neoplasms. Since conventional clear cell carcinomas are highly vascular, we evaluated the association between vascular flow within a renal mass on pre-operative color and/or power Doppler ultrasonography (CDUS) and surgical pathology. Methods: Nephrectomies performed at our institution between 1/2001 and 12/2004 were retrospectively evaluated. Detection of flow within the renal mass on CDUS was defined as vascular flow. A prospective validation study was performed from 1/2005 to 10/2005, and a nomogram predicting clear cell histology created using vascular flow along with clinical and radiologic parameters. Results: Of 299 renal lesions in the retrospective cohort, 210 (70%) had evidence of vascular flow, including 156 of 169 (92%) conventional clear cell carcinomas (p &lt; 0.0001). On logistic regression analyses, vascular flow was associated with conventional clear cell histology with an odds ratio of 16.9, CI: 8.7–32.8, p &lt; 0.0001. These findings were validated prospectively in 97 patients; CDUS detected vascular flow in 54 of 65 (83%) renal masses with conventional clear cell histology (p &lt; 0.0001) and was associated with an odds ratio of 10.8 (95% CI 4.0–29.0; p &lt; 0.0001). On multivariable analyses, vascular flow was still a statistically significant predictor of conventional clear cell histology. A nomogram incorporating vascular flow along with clinical and radiologic variables (clinical size, patient gender and age) to predict conventional clear cell histology was constructed on the retrospective cohort and validated on the prospective data set (concordance index 0.82 and 0.76 respectively). Conclusions: Vascular flow within a renal mass detected by CDUS is strongly associated with conventional clear cell histology with an odds ratio of 10.8–16.9. A nomogram incorporating vascular flow on CDUS and clinical and radiographic parameters may aid in the non-invasive characterization of renal lesions. [Table: see text] No significant financial relationships to disclose.
Use of Positron Emission Tomography to Detect Recurrence and Associations With Survival in Patients With Lung and Esophageal Cancers
Authors: Mark A. Healy, Huiying Yin, Rishindra M. Reddy, Sandra L. Wong
Journal: JNCI Journal of the National Cancer Institute (2016)

Positron emission tomography (PET) scans are often used in cancer patients for staging, restaging, and monitoring for treatment response. These scans are also often used to detect recurrence in asymptomatic patients, despite a lack of evidence demonstrating improved survival. We sought to evaluate utilization of PET for this purpose and relationships with survival for patients with lung and esophageal cancers. Using national Surveillance, Epidemiology, and End Results (SEER) and Medicare-linked data, we identified incident patient cases from 2005 to 2009, with follow-up through 2011. We identified cohorts with primary lung (n = 97 152) and esophageal (n = 4446) cancers. Patient and tumor characteristics were used to calculate risk-adjusted two-year overall survival. Using Medicare claims, we examined PET utilization in person-years (to account for variable time in cohorts), excluding scans for staging and for follow-up of CT findings. We then stratified hospitals by quintiles of PET utilization for adjusted two-year survival analysis. All statistical tests were two-sided. There was statistically significant variation in utilization of PET. Lowest vs highest utilizing hospitals performed .05 (SD = 0.04) vs 0.70 (SD = 0.44) scans per person-year for lung cancer and 0.12 (SD = 0.06) vs 0.97 (SD = 0.29) scans per person-year for esophageal cancer. Despite this, for those undergoing PET, lowest vs highest utilizing hospitals had an adjusted two-year survival of 29.0% (SD = 12.1%) vs 28.8% (SD = 7.2%) for lung cancer ( P = .66) and 28.4% (SD = 7.2%) vs 30.3% (SD = 5.9%) for esophageal cancer ( P = .55). Despite statistically significant variation in use of PET to detect tumor recurrence, there was no association with improved two-year survival. These findings suggest possible overuse of PET for recurrence detection, which current Medicare policy would not appear to substantially affect.
Abstract 15753: High-Sensitivity Cardiac Troponin T and Secondary Events in Outpatients with Coronary Heart Disease: Data from the Heart and Soul Study
Authors: Alexis L Beatty, Ivy A Ku, Kaiser Permanente, Robert H Christenson, Christopher R DeFilippi, Nelson B Schiller, Mary A Whooley
Journal: Circulation (2012)

Alexis L Beatty, 2012 Finalist and Presenting Author
<b>Interlinked mental and physical health problems cost NHS more than £11bn a year</b>
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Interlinked psychological and physical health problems are costing the NHS more than £11bn (€14.2bn; $15.6bn) a year, a figure that could be reduced by better integration of services, says a new report from the healthcare think tank the King’s Fund.1

The report also argues that integrating physical and mental healthcare could improve health outcomes for patients.

The fund estimates that £11bn is the collective cost each year of high rates of mental ill …
PWE-057 Mindfulness based cognitive therapy for inflammatory bowel disease: the results from a pilot randomised control trial
Authors: M Schoultz, I Atherton, AJ Watson
Journal: Gut (2015)

<h3>Introduction</h3> Due to the relapsing nature of the disease, rates of anxiety and depression among inflammatory bowel disease (IBD) patients are higher than in the general population. Prolonged effect of such comorbidities has been associated with poorer quality of life (QoL) and exacerbation of IBD symptoms. Mindfulness-Based Cognitive Therapy (MBCT) is an evidence-based psychological group program designed to help manage stress and depressive symptoms in depressed patients, however, no previous randomised controlled trial (RCT) has tested its possible effects on IBD patients. <h3>Aim</h3> The aim of this study was to pilot the MBCT program with IBD patients and evaluate the feasibility of conducting a larger RCT testing the effectiveness of MBCT on depression and anxiety for IBD patients. <h3>Method</h3> IBD patients from gastroenterology outpatient clinics at two Scottish NHS Boards were randomly allocated to MBCT intervention group (n = 22) or wait-list control group (n = 22). Both groups completed a baseline, post intervention and six months follow up assessments. A post intervention survey was conducted to assess the acceptability of the intervention and trial procedures for IBD patients. Primary outcome was to assess feasibility and acceptability of MBCT intervention. Secondary outcome was to assess any mean differences between baseline and each of the 2 subsequent visits between the groups on depression, anxiety, quality of life, mindfulness and disease activity scores. <h3>Results</h3> 53 (15%) IBD patients responded to the invitation to participate in the study. 44 (83%) of respondents were eligible and consented to participate in the study. The main reason for ineligibility was active disease symptoms, planned surgery and incompatibility with group schedule. 24 (56%) completed post intervention and follow up data. Participant survey indicated that trial procedures, including recruitment, randomisation and research instruments were acceptable. At post intervention and follow up, depression (F=3,975, p = 0.027), trait anxiety (F=3,286, p = .048) and dispositional mindfulness (F=3,998, p = 0.034) scores showed significant improvement in the MBCT group when compared to the control. <h3>Conclusion</h3> The results from this trial suggest that conducting a full scale RCT testing the effectiveness of MBCT program for IBD patients is both feasible and acceptable. Improvement in depression, trait anxiety and dispositional mindfulness scores are promising when coupled with patients reporting perceived improvement of their quality of life. <h3>Disclosure of interest</h3> None Declared.
Government has no credible plan to plug NHS funding “black hole,” MPs warn
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The government is yet to produce a convincing plan to tackle the NHS funding crisis and plug the financial “black hole” facing the service, a report from the House of Commons Public Accounts Committee has warned.

In the report,1 MPs said that the government had not acted quickly enough to keep acute hospital trusts in financial balance or set out credible plans for closing the £22bn efficiency gap that the NHS faces by 2020-21.

The committee highlighted that NHS trust and foundation trust finances had deteriorated, from a combined £592m surplus in 2012-13 to a net deficit of £843m in 2014-15. It warned that deficits could reach £2.5bn by the end of 2015-16, which was …
The impact of communicating genetic risks of disease on risk-reducing health behaviour: systematic review with meta-analysis
Authors: Gareth J Hollands, David P French, Simon J Griffin, A Toby Prevost, Stephen Sutton, Sarah King, Theresa M Marteau
Journal: BMJ (2016)

To assess the impact of communicating DNA based disease risk estimates on risk-reducing health behaviours and motivation to engage in such behaviours.Systematic review with meta-analysis, using Cochrane methods.Medline, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials up to 25 February 2015. Backward and forward citation searches were also conducted.Randomised and quasi-randomised controlled trials involving adults in which one group received personalised DNA based estimates of disease risk for conditions where risk could be reduced by behaviour change. Eligible studies included a measure of risk-reducing behaviour.We examined 10,515 abstracts and included 18 studies that reported on seven behavioural outcomes, including smoking cessation (six studies; n=2663), diet (seven studies; n=1784), and physical activity (six studies; n=1704). Meta-analysis revealed no significant effects of communicating DNA based risk estimates on smoking cessation (odds ratio 0.92, 95% confidence interval 0.63 to 1.35, P=0.67), diet (standardised mean difference 0.12, 95% confidence interval -0.00 to 0.24, P=0.05), or physical activity (standardised mean difference -0.03, 95% confidence interval -0.13 to 0.08, P=0.62). There were also no effects on any other behaviours (alcohol use, medication use, sun protection behaviours, and attendance at screening or behavioural support programmes) or on motivation to change behaviour, and no adverse effects, such as depression and anxiety. Subgroup analyses provided no clear evidence that communication of a risk-conferring genotype affected behaviour more than communication of the absence of such a genotype. However, studies were predominantly at high or unclear risk of bias, and evidence was typically of low quality.Expectations that communicating DNA based risk estimates changes behaviour is not supported by existing evidence. These results do not support use of genetic testing or the search for risk-conferring gene variants for common complex diseases on the basis that they motivate risk-reducing behaviour.This is a revised and updated version of a Cochrane review from 2010, adding 11 studies to the seven previously identified.
Histone Acetyltransferase Activity of p300 Is Required for Transcriptional Repression by the Promyelocytic Leukemia Zinc Finger Protein.
Authors: Fabien Guidez, Louise Howell, Mark Isalan, Marek Cebrat, Rhoda M. Alani, Sarah Ivins, Sarah Pierce, Philip A. Cole, Jonathan D. Licht, Arthur Zelent
Journal: Blood (2004)
Final results of the National Patient Impact Initiative
Authors: K. W. Tauer, B. V. Fortner, L. Zhu, L. Ma, L. S. Schwartzberg
Journal: Journal of Clinical Oncology (2005)

8128 Background: Availability of darbepoetin alfa and pegfilgrastim provide management for chemotherapy-induced anemia (CIA) and neutropenia (CIN) in cancer patients (pts) with fewer doses. However, little information is available regarding impact of CIA/CIN visits on pts and caregivers. To define the impact of CIA/CIN treatment visits on pts and caregivers. Methods: Using a cross-sectional survey design, eligible pts had a cancer diagnosis, were receiving chemotherapy (ctx), and received either an erythropoietic agent or growth colony-stimulating factor within a month prior to the survey. A semi-structured interview of pt characteristics, impact of CIA/CIN management visits on pt/caregiver time, pt activities, and caregiver support activities were captured. Results: Final report data from 15,842 cancer pts (mean age 62 yrs, range 18–99) from 651 outpatient oncology clinics were analyzed. Most common ctx schedule was Q3W (36.8%). Most (77.4%) received an erythropoietic agent (42.4% darbepoetin alfa, 35.2% epoetin alfa). Practices reported almost all (97%) Epoetin alfa is given Q1W whereas the majority (80%) of darbepoetin alfa is given on Q2W dosing. Of 11,131 pts reporting an anemia treatment visit, mean time (SD) required was 2 hr 12 min (3.10 hr) for pts and 1 hr 18 min (2.51 hr) for caregivers. Most (59.6%) received growth colony stimulating factor (34.3% pegfilgrastim, 22.6% filgrastim, 2.6% sargramostim). An average of 6.35 days of hospitalization for febrile neutropenia, 3 days for outpatient IV antibiotics, and 6 days for filgrastim were reported. Of 9353 pts reporting a CIN treatment visit, including nadir check, mean time (SD) required for one visit was 1 hr 59 min (2.58 hr) for pts and 1 hr 9 min (2.33 hr) for caregivers. Pts reported canceling, altering or postponing paid work time (24%), time with friends/family (60%), hobbies (50%) and vacation (49%) because of clinic visits. They reported needing help with transportation (80%), work coverage (17%), and errands (79%) because of clinic visits. Conclusions: Supportive care visits frequently thought of as being inconsequential have a major impact on pts and caregivers. Less frequent CIA/CIN management visits should lead to reduced pt/caregiver burden and may significantly improve quality of life. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen
Effectiveness of Prevention Strategies for Contrast-Induced Nephropathy
Authors: Rathan M. Subramaniam, Catalina Suarez-Cuervo, Renee F. Wilson, Sharon Turban, Allen Zhang, Cheryl Sherrod, Jonathan Aboagye, John Eng, Michael J. Choi, Susan Hutfless, Eric B. Bass
Journal: Annals of Internal Medicine (2016)

Background: N-acetylcysteine, sodium bicarbonate, statins, and ascorbic acid have been studied for reducing contrast-induced nephropathy (CIN). Purpose: To evaluate the comparative effectiveness of interventions to reduce CIN in adults receiving contrast media. Data Sources: MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and Scopus databases through June 2015. Risk of bias and overall strength of evidence (SOE) of studies were assessed. Study Selection: Randomized, controlled trials of N-acetylcysteine, sodium bicarbonate, statins, or ascorbic acid that used intravenous (IV) or intra-arterial contrast media and defined CIN with enough data for meta-analysis. Data Extraction: Two reviewers independently extracted data and assessed study quality. Data Synthesis: Low-dose N-acetylcysteine plus IV saline compared with IV saline (risk ratio [RR], 0.75 [95% CI, 0.63 to 0.89]; low SOE), N-acetylcysteine plus IV saline compared with IV saline in patients receiving low-osmolar contrast media (RR, 0.69 [CI, 0.58 to 0.84]; moderate SOE), and statins plus N-acetylcysteine plus IV saline versus N-acetylcysteine plus IV saline (RR, 0.52 [CI, 0.29 to 0.93]; low SOE) had clinically important and statistically significant benefits. The following 3 comparisons suggested a clinically important difference that was not statistically significant: sodium bicarbonate versus IV saline in patients receiving low-osmolar contrast media (RR, 0.65 [CI, 0.33 to 1.25]; low SOE), statins plus IV saline versus IV saline (RR, 0.68 [CI, 0.39 to 1.20]; low SOE), and ascorbic acid versus IV saline (RR, 0.72 [CI, 0.48 to 1.01]; low SOE). Strength of evidence was generally insufficient for comparisons of the need for renal replacement, cardiac events, and mortality. Limitation: Too few studies were done in patients receiving IV contrast media. Conclusion: The greatest reduction in CIN was seen with N-acetylcysteine plus IV saline in patients receiving LOCM and with statins plus N-acetylcysteine plus IV saline. Primary Funding Source: Agency for Healthcare Research and Quality.
Identification of Rare Variants in <i>ATP8B4</i> as a Risk Factor for Systemic Sclerosis by Whole‐Exome Sequencing
Authors: Li Gao, Mary J. Emond, Tin Louie, Chris Cheadle, Alan E. Berger, Nicholas Rafaels, Candelaria Vergara, Yoonhee Kim, Margaret A. Taub, Ingo Ruczinski, Stephen C. Mathai, Stephen S. Rich, Deborah A. Nickerson, Laura K. Hummers, Michael J. Bamshad, Paul M. Hassoun, Rasika A. Mathias, Kathleen C. Barnes
Journal: Arthritis & Rheumatology (2015)

Objective To determine the contribution of rare variants as genetic modifiers of the expressivity, penetrance, and severity of systemic sclerosis (SSc). Methods We performed whole‐exome sequencing of 78 European American patients with SSc, including 35 patients without pulmonary arterial hypertension (PAH) and 43 patients with PAH. Association testing of case–control probability for rare variants was performed using the unified sequence kernel association test with optimal kernel weighting and small sample adjustment by comparing all SSc patients with a reference population of 3,179 controls from the Exome Sequencing Project 5,500 exome data set. Replication genotyping was performed in an independent sample of 3,263 patients (415 patients with SSc and 2,848 controls). We conducted expression profiling of messenger RNA from 61 SSc patients (19 without PAH and 42 with PAH) and 41 corresponding controls. Results The ATP8B4 gene was associated with a significant increase in the risk of SSc ( P = 2.77 × 10 −7 ). Among the 64 ATP8B4 variants tested, a single missense variant, c.1308C&gt;G (F436L, rs55687265), provided the most compelling evidence of association ( P = 9.35 × 10 −10 , odds ratio [OR] 6.11), which was confirmed in the replication cohort ( P = 0.012, OR 1.86) and meta‐analysis ( P = 1.92 × 10 −7 , OR 2.5). Genes involved in E3 ubiquitin‐protein ligase complex ( ASB10 ) and cyclic nucleotide gated channelopathies ( CNGB3 ) as well as HLA–DRB5 and HSPB2 (heat‐shock protein 27) provided additional evidence of association ( P &lt; 10 −5 ). Differential ATP8B4 expression was observed among the SSc patients compared to the controls ( P = 0.0005). Conclusion ATP8B4 may represent a putative genetic risk factor for SSc and pulmonary vascular complications.