tbuckley/cabot-search huggingface dataset:
Latino ethnicity, immigrant status, and preference for life-extending end-of-life cancer care.
Authors: Ana Isabel Tergas, Holly Gwen Prigerson, Megan Johnson Shen, Paul K Maciejewski
Journal: Journal of Clinical Oncology (2017)

10028 Background: Latino advanced cancer patients are less likely to engage in advance care planning, use hospice services, and receive end-of-life (EOL) care in line with their preferences compared to non-Latino advanced cancer patients. Little is known about how immigration status influences preference for life-extending care (LEC) at the EOL. Methods: Data were derived from two sequential multi-institutional, longitudinal cohort studies of patients with advanced cancer recruited from 2002 – 2008 (Coping with Cancer I [CwC-1]) and 2010 – 2015 (Coping with Cancer II [CwC-2]). Multiple logistic regression analysis was used to estimate effects of immigrant status and CwC cohort among Latinos, and effects of ethnicity and CwC cohort among US-born Latinos and non-Latino whites, on preference for LEC at the EOL. Results: Of the 760 studied cancer patients, 661 were US-born non-Latino (US non-L), 34 were US-born Latino (USL) and 65 were Latino immigrants (LI). LI were less educated (mean years of education: 7.8 years) than USL (11.1 years), who were in turn less educated than US non-L (13.7 years). Far fewer LI had insurance compared to USL (18.5% vs. 64.7%, respectively; p &lt; 0.001), and fewer USL had insurance compared to US non-L (64.7% vs. 81.4%, respectively; p = 0.017). Within CwC-2, LI had higher odds of preferring LEC over comfort care compared to USL (adjusted odds ratio [AOR] = 9.4; 95% CI: 1.2, 72.4), and USL had lower odds of preferring LEC compared to US non-L (AOR = 0.3; 95% CI: 0.1, 1.0). LI from CwC-2 had higher odds of preferring LEC compared to LI from CwC-1 (AOR = 11.4; 95% CI: 2.7, 48.4), but there was no difference between USL from CwC-2 and USL from CwC-1. US non-L from CwC-2 had higher odds of preferring LEC compared to US non-L from CwC-1 (AOR = 3.9; 95% CI: 2.6, 5.9). Within CwC-1, there was no difference in LEC preference between LI and USL, nor between USL and US non-L. Conclusions: Immigrant status has a strong effect on preference for life-extending care among the more recent cohort of Latino cancer patients. Preference for life-extending care appears to have increased significantly over time for Latino immigrants, but remained unchanged for US-born Latinos. Latino immigrants may increasingly want life-extending care near death.
Abstract 15570: Direct Evidence of Endo-Epicardial Dissociation of the Atrial Wall in Patients With Longstanding Persistent Atrial Fibrillation
Authors: Natasja de Groot, Lisette vd Does, Ameeta Yaksh, Paul Knops, Pieter Woestijne, Charles Kik, Ad Bogers, Maurits Allessie
Journal: Circulation (2015)

Introduction: Transition of paroxysmal to longstanding persistent atrial fibrillation (LsPAF) is associated with progressive longitudinal dissociation in conduction and a higher incidence of focal fibrillation waves. The aim of this study was to provide direct evidence that the substrate of LsPAF consists of an electrical double-layer of dissociated waves, and that focal fibrillation waves are caused by endo-epicardial breakthrough. Hypothesis: LsPAF in humans is caused by electrical dissociation of the endo- and epicardial layer. Methods: Intra-operative mapping of the endo- and epicardial right atrial wall was performed in 9 patients with induced (N=4), paroxysmal (N=1), persistent (N=2) or longstanding-persistent AF (N=2). A clamp of two rectangular electrode-arrays (128 electrodes; inter-electrode distance 2mm) was introduced through an incision in the right atrial appendage. Series of 10 seconds of AF were analyzed and the incidence of endo-epicardial dissociation (≥15ms) was determined for all 128 endo-epicardial recording sites. Results: In patients with LsPAF the averaged degree of endo-epicardial dissociation was highest (24.9% vs. 5.9%). Using strict criteria for breakthrough (presence of an opposite wave within 4mm and &lt;15ms before the origin of the focal wave), the far majority (77%) of all focal fibrillation waves could be attributed to endo-epicardial excitation. Conclusions: During LsPAF considerable differences in activation of the right endo- and epicardial wall exist. Endo-epicardial fibrillation waves that are out of phase, may conduct transmurally and create breakthrough waves in the opposite layer. This may explain the high persistence of AF and the low succes rate of ablative therapies in patients with LsPAF.
Airlie House legend
Authors: Martin H. Steinberg, Alan N. Schechter
Journal: American Journal of Hematology (2018)

In the late 1980’s (probably in 1988), the National Heart, Lung and Blood Institute convened a “think tank” at Airlie House in Northern Virginia to discuss the developmental therapeutic landscape for sickle cell disease. The participants, most of whom are shown in the accompanying photograph, included in Row 1 (left to right), William Eaton, Marilyn Gaston, Ronald Nagel, Samuel Charache, H. Franklin Bunn, Clarice Reid, Yves Beuzard, Max Perutz, Donald Abraham, Jean Smith, and Alan Schechter, and in Row 2, Bernard Forget, Herbert Meiselman, Eugene Orringer, Martin Steinberg, Charles Wells, Mohandas Narla, Robert Josephs, Arthur Nienhuis, and George Stamatoyannopoulos. David Nathan also participated. John Hercules from NHLBI largely planned and organized the meeting but died in March 1988 (Image 1). These clinicians, investigators and NIH leaders were responsible for establishing much of the groundwork in basic, translational and clinical science that have led to treatments for sickle cell disease, some now approved and others likely to be approved. By the time of this meeting Perutz had established the basis of many of the functions of hemoglobin and shared a Nobel Prize in 1962 for determining the molecular structure of this molecule. His work provided an understanding of how hemoglobin variants cause disease and how they might be therapeutically targeted. Studies stimulated by this meeting include the effective use of a fetal hemoglobin inducing agent, hydroxyurea that has decreased morbidity and mortality of sickle cell anemia patients, the continuing development of agents that modulate intercellular adhesive interactions, a deepening appreciation of the effects of red cell hydration on disease pathophysiology and the beginnings of gene therapy for hemoglobinopathies.
Abstract 16276: A Web-based Tool for Predicting Acute Kidney Injury in ST-elevation Myocardial Infarction
Authors: Benjamin R Zambetti, Robert T Ellis, Inyong Hwang, Mason Chumpia, Mark R Heckle, Blake Smith, Mary T Crouse, Nephertiti Efeovbokhan, Fridtjof Thomas, Rami N Khouzam, Uzoma N Ibebuogu, Guy L Reed
Journal: Circulation (2015)

ST-elevation myocardial infarction (STEMI) requires emergent diagnostic catheterization and therapeutic percutaneous coronary intervention. These therapies may cause acute kidney injury (AKI), a serious procedural complication that contributes to morbidity and mortality in STEMI patients. Identifying patients at risk for renal complications may save lives and reduce healthcare costs, but there is no validated tool for predicting AKI in STEMI patients. Methods: The UT-Methodist STEMI program is a racially diverse series of 1144 consecutive patients. We derived and validated the UT-AKI score to predict the risk of AKI in patients referred for STEMI (and not currently on dialysis). AKI was categorized by the modified AKI Network and RIFLE indices. The UT-AKI score was derived from logistic regression analysis performed on a randomly selected derivation dataset using variables with significant univariate relationships to AKI and markers of renal function. Receiver operator characteristic (ROC) curves for the UT-AKI were assessed in the derivation and validation datasets. Statistical significance was measured by appropriate parametric and non-parametric tests; a p&lt;0.05 was considered significant. Results: The incidence of AKI was similar in patients undergoing diagnostic catheterization with or without PCI (12% vs. 14%, p=0.34). ROC curve analysis of the validation data set showed that the UT-AKI score (AUC 0.76 (95% CI 0.70-0.82)) was significantly better at classifying patients at risk for AKI than the ACEF (AUC 0.65 (95% CI: 0.58-0.73)), AGEF (AUC 0.65 (95% CI: 0.58-0.72)), or Mehran (AUC 0.67 (95% CI: 0.59-0.75)). The classification accuracy for the UT-AKI index was comparable for milder and severe forms of AKI. Conclusions: In the largest analysis of STEMI patients to date, we found no significant difference in the risk of AKI from PCI vs. diagnostic catheterization. The validation study indicates that the UT-AKI index was significantly better than other scores at classifying which patients will develop AKI. Accurate prediction of AKI may help physicians to personalize therapies and develop novel strategies to reduce kidney injury in patients with STEMI.
Olanzapine and palonosetron without dexamethasone for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: A proof-of-concept trial.
Authors: Hee Jun Kim, Joo Young Ha, Edward Hyunseung Oh, Song Ee Park, Jun Ho Yi, Joung Soon Jang, In Gyu Hwang
Journal: Journal of Clinical Oncology (2018)

e22204 Background: Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. A combination of serotonin antagonist, olanzapine, and corticosteroid has proven effective against this problem. However, concerns exist regarding the potential toxicity of the use of multiple-day dexamethasone to control CINV. The purpose of this study was to determine the safety and efficacy of an antiemetic regimen of olanzapine (10 or 5mg) and palonosetron without dexamethasone to control acute (0-24 h), delayed (24-120 h) and overall (0-120 h) CINV in patients receiving moderately emetogenic chemotherapy (MEC). Impact on life was assessed using the MD Anderson Symptom Inventory (MDASI). Methods: 55 patients were enrolled. The study antiemetic regimen is combined olanzapine and palonosetron without dexamethasone in patients receiving MEC as a first cycle. Patients continued olanzapine for 4days after chemotherapy administration. A daily patient diary recording episodes of emesis and severity of nausea was then kept for 5 days. In addition, the M.D. Anderson Symptom Inventory (MDASI) was used to assess the effect of CINV on a patient's QoL. Results: Fifty-eligible and evaluable patients (median age 56.2 years, range 25–76) with solid cancer in this study. Complete response rate was 72% for the acute period and 80% for the delayed period and 64% for the overall period. No nausea rate is 70 % (acute), 70 % (delayed) and 64 (overall). Olanzapine, 5mg was similar effect with 10mg. Among 50, 68 % of patients in this study had somnolence during chemotherapy. Conclusions: This study showed a combination of olanzapine and palonosetron without dexamethasone was effective for protection against both acute and delayed CINV after MEC. Randomized trials comparing to a standard regimen including dexamethasone is warranted. Clinical trial information: NCT02970643.
TCT-104 Comparative Data on the Use of Intracardiac and Transesophageal Echocardiography for Left Atrial Appendage Occlusion in the Amulet Observational Study
Authors: Jens Erik Nielsen-Kudsk, Sergio Berti, Ole De Backer, Daniel Aguirre, Gaetano Fassini, Ignacio Cruz-Gonzalez, Giuseppe Grassi, Claudio Tondo
Journal: Journal of the American College of Cardiology (2018)
Barney Carroll: the conscience of psychiatry
Authors: Allen Frances, Barney Carroll
Journal: BMJ (2018)

Credit: Duke University

A pioneer in biological psychiatry, more recently Bernard Carroll (‘‘Barney’’) became a withering critic of its compromised ethics and corruption by industry. Shortly before his death, he helped prepare this obituary—his last chance to help correct the perverse incentives that too often influence the conduct and reporting of scientific research.

Barney’s scientific contribution to psychiatric research was to introduce neuroendocrine techniques. He independently discovered the value of the dexamethasone suppression test (DST) as a biomarker of melancholia—the classic, biologically driven subtype of depression. This was the first, and remains one of very few, biomarkers in psychiatry. Barney’s 1981 paper on the DST was among the most highly cited papers in psychiatry. Its impact was immediate, with many replications and extensions.

Another of Barney’s enduring contributions was to educate colleagues in the discipline of proper clinical decision making. He clarified the Bayesian principle that context counts—that is, prior conditional probabilities greatly influence the utility of any clinical feature or laboratory test in making a diagnosis. Throughout medicine, biomarkers and clinical diagnostic features perform with much greater utility in high risk groups than in general populations.

Barney criticised the Diagnostic and Statistical Manual for innumerate failures to clarify the performance of diagnostic criteria and pointed out that candidate biomarkers often outperformed accepted symptomatic diagnostic criteria.

A rigorous scientific …
Angiotensin system inhibitors during induction chemotherapy for esophageal adenocarcinoma: Analysis of survival.
Authors: Abraham Geller, Michael Lanuti, Henning A Gaissert, Cameron D Wright, Dean M Donahue, Harald Ott, Hui Zheng, Rebecca Suk Heist, Melin Janardan Khandekar, Rakesh K. Jain, Douglas J Mathisen, Ashok Muniappan
Journal: Journal of Clinical Oncology (2018)

e16066 Background: Renin-angiotensin system (RAS) signaling affects tumorigenesis and treatment susceptibility of various cancers. We investigate the impact of angiotensin–system inhibitors (ASIs) on the survival of patients with locally advanced esophageal adenocarcinoma (EAC) undergoing curative treatment. Methods: EAC patients receiving trimodal therapy from 2002 to 2017 at a single institution were included. Clinical and treatment details were obtained from medical records. Primary outcomes were overall survival (OS) and disease-free survival (DFS), measured from date of surgery until death (OS & DFS) or first recurrence (DFS only). Patients taking an ACE inhibitor or ARB during induction were considered ASI users. Survival was analyzed with the Kaplan–Meier and Cox Proportional Hazards methods. Patient characteristics were compared with Student’s T and chi square tests. Results: 375 patients with EAC were included. 92 patients (25%) were ASI users (ASI+), 283 patients (75%) were ASI non-users (ASI-). Median follow–up was 32.4 months. Compared to ASI-, ASI+ were older (mean age 61 vs. 64), and had higher rates of hypertension (30% vs. 96%), cerebrovascular disease (1% vs. 6%), diabetes (11% vs. 28%), and COPD (3% vs. 9%) (P < .05 for all). Distribution of tumor stages was similar between groups (P = .3). Compared to ASI-, ASI+ showed improved median OS (30 vs. 59 months, P = .025) and DFS (18 vs. 25 months, P = .032). After controlling for age and comorbidities, ASI+ showed improved OS (HR .633, P = .031) and DFS (HR .661, P = .036) compared to ASI-. Conclusions: RAS inhibition with ASIs during cancer treatment is associated with improved outcomes, which may be related to increased drug delivery, enhanced tumor immunity, or direct inhibition of RAS–dependent tumorigenesis. Our study suggests that ASIs taken during induction chemoradiotherapy for locally advanced EAC may provide additional survival benefit. These findings justify further investigation with prospective studies. Cox models of overall and disease–free survival FACTOR OS DFS HR P value HR P value Age 1.01 .336 1.00 .874 HTN 1.05 .793 1.11 .517 CVD 1.20 .691 .803 .671 Diabetes 1.01 .972 1.02 .901 COPD .912 .805 .895 .752 ASI use .633 .031 .661 .036
Demographic predictors of missed follow up among solid tumor patients treated at a large multi-site academic institution.
Authors: Jordan A. Holmes, Saleh Rachidi, Susannah Ellsworth, Richard C. Zellars, Tim Lautenschlaeger
Journal: Journal of Clinical Oncology (2018)

e18675 Background: After treatment for cancer regular follow up may detect early recurrence that can lead to better salvage therapy outcomes. However, little is known about how many patients miss follow up appointments and what groups of patients are more likely to be lost to follow up. Using data from 1999-2016 from a large multi-site institution we examined the proportion of patients who were lost to follow up and demographic predictors of being lost to follow up. Methods: Appointment data for patients with solid tumors diagnosed in the Indiana University health care system was linked with cancer registry data. Patients were classified as having a missed follow up if they had a no show, canceled or rescheduled appointment without a subsequent attended appointment with 60 days. Appointments were excluded if they were within 180 days of patient death. Cancer registry data included disease site, patient race, age and census level demographics including income and rural/urban continuum. Univariate comparisons were performed using Chi squared, and a multivariable logistic regression model adjusting for race, age, income, rural/urban, insurance and disease site was constructed. Results: Data from 24,117 individual patients and 355,163 appointments were analyzed. Median age was 60 years, 11% of the patients were African American (AA) and 7% of patients lived in the most rural (non-core) areas. Overall 14.9% of patients had at least one missed follow up. On univariate analysis AA patients, patient without insurance or with Medicaid, patients from lower income counties and patients from non-core areas were more likely to have a missed follow up (p < 0.001 for each). On multi-variable modeling AA patients (OR 1.19, p = 0.004), patients with Medicaid (OR 1.17, p = 0.017) and those from non-core rural areas (OR 1.20, p = 0.024) remained more likely to have missed follow up appointments. Conclusions: A small but significant proportion of cancer patients miss scheduled follow up appointments without rescheduling, and this appears to be more common among vulnerable patient populations. More research is needed on how to address disparities in follow up care, and how missed follow up might affect survival
Cost-effectiveness of omalizumab in chronic spontaneous urticaria
Authors: T.A. Kanters, H.B. Thio, L. Hakkaart
Journal: British Journal of Dermatology (2018)

Chronic spontaneous urticaria (CSU) is a skin disease which causes itchy hives that last for at least 6 weeks, and without an obvious external trigger. CSU can affect people's quality of life and performance at school and work. CSU also has an impact on society and the economy, due to healthcare costs, time off work, and so on. International recommendations advise that CSU is first treated with antihistamines, the dosage of which can be increased (updosed). Some patients also receive leukotriene antagonists (LTRAs). If this does not work, doctors can prescribe drugs called omalizumab or ciclosporin. Ciclosporin has been shown to be effective, but it is linked with potential side‐effects. Omalizumab is an add‐on treatment; patients also receive antihistamines and LTRAs. Omalizumab is an effective treatment for CSU, as it reduces the symptoms. However, omalizumab is also more expensive than existing treatments. To oppose rising healthcare costs, healthcare authorities increasingly use cost‐effectiveness as a factor when deciding which treatments should be recommended. In this study, a way of measuring cost‐effectiveness (a model) was built to assess the cost‐effectiveness of omalizumab. The objective of this study, carried out by researchers in the Netherlands, was to determine the cost‐effectiveness of omalizumab compared to standard care, namely updosed antihistamines. The study looked at quality of life, costs within the healthcare sector, patient and family costs (informal care costs) and costs to other sectors. Drug costs per 4 weeks of treatment with omalizumab were €745, compared with drug costs for standard care of only €32. In addition, administration costs of €14 per injection were applicable for omalizumab. However, costs in other sectors (i.e. productivity costs, such as being able to work) constituted the largest share of the total costs for both treatment options, but were lowest for omalizumab. Savings on these indirect costs largely compensated for increased drug costs. In this study, omalizumab was shown to be more effective than SoC, but also more costly. However it was still deemed cost effective.
Abstract 15497: Hematopoietic PI3-Kinase delta-Deficiency Causes Altered Macrophage and Regulatory T-cell Function and Aggravates Atherosclerosis in LDLR-/- Mice
Authors: Mario Zierden, Christopher Millarg, Marius Vantler, Eva M Berghausen, Stephan Baldus, Stephan Rosenkranz
Journal: Circulation (2015)

Atherosclerosis and its consequences such as myocardial infarction and ischemic stroke remains the leading cause of death in western countries. During atherogenesis, arterial blood vessels become infiltrated by macrophages and T cells possessing inflammatory and regulatory functions. Leukocytes express the catalytic phosphoinositide 3-kinase isoform p110d (PI3Kd), exerting a key role in the regulation of immune responses including activation, differentiation and effector function. Therefore, PI3Kd represents a promising target for the modulation of inflammatory processes during atherogenesis. To investigate the role of leukocytic PI3Kd during atherogenesis, lethally irradiated LDLR-/- mice were transplanted with bone marrow from PI3Kd-/- or PI3Kd+/+ mice and were fed an atherogenic diet for 6 weeks. Hypercholesterolemic PI3Kd-/- recipient LDLR-/- mice displayed a profound reduction of peripheral B and T cells as well as strongly impaired CD4+ T-cell activation, T-helper 1 response and regulatory T-cell numbers in paraaortic lymph nodes and spleen compared with PI3Kd+/+ transplanted controls. Surprisingly, the profoundly impaired PI3Kd-deficient immune system caused a substantial aggravation of atherosclerosis in LDLR-/- mice. Atherosclerotic lesion area at the aortic root and whole aorta of PI3Kd-/- recipient LDLR-/- mice was significantly increased by 72% and 218% compared with PI3Kd+/+ recipients, respectively (n = 10-20; P &lt; 0.001). Importantly, atherosclerotic lesions of PI3Kd-/- transplanted LDLR-/- mice were characterized by a lower fraction of CD4+ T cells and a higher proportion of macrophages compared with controls despite unaltered circulating monocyte subsets. Moreover, PI3Kd-deficient regulatory T cells and macrophages exhibited a strongly impaired suppressive capacity and an increased inflammatory polarization, respectively. In summary, we demonstrate that hematopoietic PI3Kd plays a crucial role in regulating innate and adaptive immune responses within the arterial wall by exerting protective functions during atherogenesis. Current studies aim to dissect PI3Kd-dependent mechanisms that modulate inflammatory and regulatory processes in multiple stages of atherosclerosis.