tbuckley/cabot-search huggingface dataset:
Changes in the setting of first consults to palliative and supportive care over a 7-year period.
Authors: Bernard Lobato Prado, Ali Haider, Syed M. Naqvi, Roberto Carmagnani Pestana, Janet L. Williams, Seyedeh Dibaj, Diane D. Liu, Julio A. Allo, Vera J De la Cruz, Eduardo Bruera
Journal: Journal of Clinical Oncology (2018)

86 Background: Optimal benefits from palliative cancer care (PC) are achieved when first consults (PC1) occur early, ideally in the outpatient setting. Late PC1, such as those occurring in the intensive care unit (ICU), limit the benefits of PC and are a poor indicator of the integration of PC and oncology. Our aim was to determine the proportion of PC1 over time in three clinical settings: outpatient clinic (OPC), ICU, and inpatient non-ICU (IP). We also examined patients’ demographic and clinical characteristics and the timing of PC access (from PC1 to death or last contact) by the setting of PC1. Methods: We evaluated consecutive administrative/billing records to ascertain the annual number of PC1 and its distribution across settings from 2011 to 2017. ICU PC1 (n = 309) and a random sample of an equal number of OPC and IP PC1 were reviewed to retrieve patients’ demographics, clinical characteristics, and date of death/last contact. The Cochran-Armitage trend test was used to determine trend differences in the proportion of PC1 among settings. Results: The total annual number of PC1 increased by 58% from 2011 (n = 2286) to 2017 (n = 3615). We found a significant decreasing trend in the proportion of PC1 at the ICU (from 2.3% in 2011 to 1% in 2017, p &lt; 0.001). There were no significant changes over time in the proportion of PC1 at OPC versus inpatient settings (p = 0.2). Hematologic cancer patients were more likely to have a PC1 at the ICU (p &lt; .001). PC1 at ICU accessed PC much later, median survival (95% CI) after PC1 in months: OPC= 7.7 (6.3 - 9.7); IP= 3.4, (2.4 - 4.5), ICU= 0.1 (0.1, 0.1), p &lt; .01). Conclusions: Over time, the total annual number of PC1 has increased and the proportion of PC1 at ICU, a very late clinical setting, is decreasing. Further efforts are needed to promote early PC referrals for patients with hematologic malignancies.
Eosinophilic dermatosis of hematologic malignancy: A retrospective cohort of 37 patients from an Italian center
Authors: Vieri Grandi, Roberto Maglie, Emiliano Antiga, Margherita Vannucchi, Chiara Delfino, Irene Lastrucci, Susanna Gunnella, Stefania Ciolli, Lavinia Quintarelli, Daniela Massi, Marzia Caproni, Nicola Pimpinelli
Journal: Journal of the American Academy of Dermatology (2018)
Disparities in access to palliative care for patients treated for gynecologic oncology.
Authors: Nora Flood, Colleen Rivard
Journal: Journal of Clinical Oncology (2018)

136 Background: Palliative care intends to improve quality of life for patients with life-threatening illness, but ethnic and linguistic minority patients have worse outcomes with palliative care. Methods: This is a single institution retrospective chart review of patients with an advanced stage or recurrent gynecologic malignancy who were seen in the clinic from 2010 to 2015. Women were defined as being from a minority group if they met one of the inclusion criteria including English not the primary language, race other than white, ethnically Hispanic/Latina, or their country of origin was not the United States. We then compared rates of referral to palliative care between those women who were deemed to be minority women as compared to those who were non-minority. We also compared the time to referral between these two groups. Results: Our study included 277 women of which 20% were categorized as minority. Demographic data between the two groups were well matched with the exception that minority women were diagnosed at a younger age and were more likely to have cervical cancer. Although not statistically significant, more minority women were referred to palliative care than non-minority (79% vs. 89%, p=0.08). In contrast, fewer minority patients were referred to palliative care at least 3 months prior to death when compared to non-minority patients (50% vs. 38%, p =0.10). There was no difference between referral location [inpatients (35% vs. 36%) and outpatients (65% vs. 64%, p=.92)] in minority versus non-minority patients. There was also no significant difference in those patients entering hospice while admitted to the hospital. Minority patients had significantly more cancer-related hospitalizations per year (0.6 vs 1.0, p value 0.02). Conclusions: Our study shows that there is a tendency towards later referral to palliative care for minority patients as compared to non-minority patients. Although more minority patients are referred to palliative care, they are hospitalized for cancer related symptoms at a significantly higher rate suggesting that perhaps their utilization of palliative care services is suboptimal.
Trends in Drug Use–Associated Infective Endocarditis and Heart Valve Surgery, 2007 to 2017
Authors: Asher J. Schranz, Aaron Fleischauer, Vivian H. Chu, Li-Tzy Wu, David L. Rosen
Journal: Annals of Internal Medicine (2018)

Background: Drug use–associated infective endocarditis (DUA-IE) is increasing as a result of the opioid epidemic. Infective endocarditis may require valve surgery, but surgical treatment of DUA-IE has invoked controversy, and the extent of its use is unknown. Objective: To examine hospitalization trends for DUA-IE, the proportion of hospitalizations with surgery, patient characteristics, length of stay, and charges. Design: 10-year analysis of a statewide hospital discharge database. Setting: North Carolina hospitals, 2007 to 2017. Patients: All patients aged 18 years or older hospitalized for IE. Measurements: Annual trends in all IE admissions and in IE hospitalizations with valve surgery, stratified by patients' drug use status. Characteristics of DUA-IE surgical hospitalizations, including patient demographic characteristics, length of stay, disposition, and charges. Results: Of 22 825 IE hospitalizations, 2602 (11%) were for DUA-IE. Valve surgery was performed in 1655 IE hospitalizations (7%), including 285 (17%) for DUA-IE. Annual DUA-IE hospitalizations increased from 0.92 to 10.95 and DUA-IE hospitalizations with surgery from 0.10 to 1.38 per 100 000 persons. In the final year, 42% of IE valve surgeries were performed in patients with DUA-IE. Compared with other surgical patients with IE, those with DUA-IE were younger (median age, 33 vs. 56 years), were more commonly female (47% vs. 33%) and white (89% vs. 63%), and were primarily insured by Medicaid (38%) or uninsured (35%). Hospital stays for DUA-IE were longer (median, 27 vs. 17 days), with higher median charges ($250 994 vs. $198 764). Charges for 282 DUA-IE hospitalizations exceeded $78 million. Limitation: Reliance on administrative data and billing codes. Conclusion: DUA-IE hospitalizations and valve surgeries increased more than 12-fold, and nearly half of all IE valve surgeries were performed in patients with DUA-IE. The swell of patients with DUA-IE is reshaping the scope, type, and financing of health care resources needed to effectively treat IE. Primary Funding Source: National Institutes of Health.
Abstract 20472: Anatomical Characteristics of the Superior Epigastric Artery for Epicardial Radiofrequency Catheter Ablation
Authors: Yuichi Nagamatsu, Shumpei Mori, Koji Fukuzawa, Kunihiko Kiuchi, Sei Fujiwara, Hiroshi Imada, Kiyohiro Hyogo, Jun Kurose, Yu Izawa, Hideya Suehiro, Tomomi Akita, Ryo Takemoto, Shinsuke Shimoyama, Ken-ichi Hirata
Journal: Circulation (2017)

Introduction: After bifurcating from the internal thoracic artery, the superior epigastric artery (SEA) exits from the thoracic cage, then runs along the costal margin. Epicardial radiofrequency ca...
Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Eleftherios P Mamounas, Hanna Bandos, Barry C Lembersky, Jong-Hyeon Jeong, Charles E Geyer, Priya Rastogi, Louis Fehrenbacher, Mark L Graham, Stephen K Chia, Adam M Brufsky, Janice M Walshe, Gamini S Soori, Shaker R Dakhil, Thomas E Seay, James L Wade, Edward C McCarron, Soonmyung Paik, Sandra M Swain, D Lawrence Wickerham, Norman Wolmark
Journal: The Lancet Oncology (2018)
High Efficacy of Lenalidomide Plus R-CHOP (R2CHOP) Combination in First Line Treatment of Activated B-Cell (ABC) DLBCL Defined Using Gene-Expression Prophyling: A Combined Analysis from Two Phase 2 Trials
Authors: Alessia Castellino, Annalisa Chiappella, Betsy Laplant, Levy D. Pederson, Giorgio Inghirami, Gianluca Gaidano, William R Macon, Alessandra Tucci, Rebecca L King, Angela Giovanna Congiu, Thomas M. Habermann, Thomas E. Witzig, Umberto Vitolo, Grzegorz S. Nowakowski
Journal: Blood (2018)
Senior stakeholder views on policies to foster a culture of openness in the English National Health Service: a qualitative interview study
Authors: Graham Paul Martin, Sarah Chew, Mary Dixon-Woods
Journal: Journal of the Royal Society of Medicine (2018)

Summary Objectives To examine the experiences of clinical and managerial leaders in the English healthcare system charged with implementing policy goals of openness, particularly in relation to improving employee voice. Design Semi-structured qualitative interviews. Setting National Health Service, regulatory and third-sector organisations in England. Participants Fifty-one interviewees, including senior leaders in healthcare organisations (38) and policymakers and representatives of other relevant regulatory, legal and third-sector organisations (13). Main outcome measures Not applicable. Results Participants recognised the limitations of treating the new policies as an exercise in procedural implementation alone and highlighted the need for additional ‘cultural engineering’ to engender change. However, formidable impediments included legacies of historical examples of detriment arising from speaking up, the anxiety arising from increased monitoring and the introduction of a legislative imperative and challenges in identifying areas characterised by a lack of openness and engaging with them to improve employee voice. Beyond healthcare organisations themselves, recent legal cases and examples of ‘blacklisting’ of whistle-blowers served to reinforce the view that giving voice to concerns was a risky endeavour. Conclusions Implementation of procedural interventions to support openness is challenging but feasible; engineering cultural change is much more daunting, given deep-rooted and pervasive assumptions about what should be said and the consequences of mis-speaking, together with ongoing ambivalences in the organisational environment about the propriety of giving voice to concerns.
AB0238 Patient-centred approach to management of inflammatory arthritis was associated with improved satisfaction of care and perceived treatment benefit
Authors: L. Attipoe, S. Virdee, J. Greenan-Barrett, D. Shah, A. Cotton, J. Guinto, J. Wilton, C. Ciurtin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Recently, there has been a paradigm shift from a paternalistic doctor-patient relationship towards more holistic, patient-centred care aimed at promoting patient autonomy. However, the effect of patient-centred care on important clinical outcomes, like patient satisfaction and disability, is unknown. <h3>Objectives</h3> To investigate how the various aspects of patients' experiences of the care they received for their inflammatory arthritis was correlated with disease activity and health satisfaction, and use this to guide our clinical practice. <h3>Methods</h3> 115 questionnaires (including 51 questions, in addition to HAQ) were randomly given to patients with inflammatory arthritis who attended rheumatology outpatient clinics at University College Hospital, London between November 2014 and January 2015 (104 were returned −90% response rate). Questions were semi-structured using a Likert scale and focused on diagnosis, symptomatology, treatment history, health status and experiences of clinic attendance. The strength of association between health satisfaction and experience of care was correlated using Spearman's correlation test (p&lt;0.05 was considered statistically significant). <h3>Results</h3> We calculated correlations between various aspects of patients' experiences of their care with other components of the questionnaire (table 1). <h3>Conclusions</h3> Patients who felt that they experienced a more patient-centred approach (through greater involvement in clinical decisions, emotional support and ease of contact with specialists) reported greater satisfaction and regarded their treatment as more efficacious. This suggests that clinicians who go beyond their role of medically managing inflammatory arthritis to provide more holistic care may improve patient-orientated health outcomes. Patients in older age groups find it easier to contact the department, perhaps because they have more free time to make and receive calls. As ease of contact is a strong predictor of overall patient satisfaction, employing ideas to increase accessibility for younger age groups, such as improved access beyond working hours may improve satisfaction. The positive correlation of HAQ with employment status and age is expected, as HAQ is the current gold standard measure of functional status. This reaffirms its accuracy in clinical practice as a measure of a functional ability. Further research into comparing patients' experience of their care with objective measures of disease activity is needed. <h3>Disclosure of Interest</h3> None declared
The theranostic promise for Neuroendocrine Tumors in the late 2010s - Where do we stand, where do we go?
Authors: Rudolf A. Werner, Alexander Weich, Malte Kircher, Lilja B. Solnes, Mehrbod S. Javadi, Takahiro Higuchi, Andreas K. Buck, Martin G. Pomper, Steven P. Rowe, Constantin Lapa
Journal: Theranostics (2018)

More than 25 years after the first peptide receptor radionuclide therapy (PRRT), the concept of somatostatin receptor (SSTR)-directed imaging and therapy for neuroendocrine tumors (NET) is seeing rapidly increasing use.To maximize the full potential of its theranostic promise, efforts in recent years have expanded recommendations in current guidelines and included the evaluation of novel theranostic radiotracers for imaging and treatment of NET.Moreover, the introduction of standardized reporting framework systems may harmonize PET reading, address pitfalls in interpreting SSTR-PET/CT scans and guide the treating physician in selecting PRRT candidates.Notably, the concept of PRRT has also been applied beyond oncology, e.g. for treatment of inflammatory conditions like sarcoidosis.Future perspectives may include the efficacy evaluation of PRRT compared to other common treatment options for NET, novel strategies for closer monitoring of potential side effects, the introduction of novel radiotracers with beneficial pharmacodynamic and kinetic properties or the use of supervised machine learning approaches for outcome prediction.This article reviews how the SSTR-directed theranostic concept is currently applied and also reflects on recent developments that hold promise for the future of theranostics in this context.
A Neutralizing Aptamer to TGFBR2 and miR-145 Antagonism Rescue Cigarette Smoke- and TGF-β-Mediated CFTR Expression
Authors: Rajib K. Dutta, Srinivasan Chinnapaiyan, Lawrence Rasmussen, S. Vamsee Raju, Hoshang J. Unwalla
Journal: Molecular Therapy (2018)

Transforming growth factor β (TGF-β), signaling induced by cigarette smoke (CS), plays an important role in the progression of airway diseases, like chronic bronchitis associated with chronic obstructive pulmonary disease (COPD), and in smokers. Chronic bronchitis is characterized by reduced mucociliary clearance (MCC). Cystic fibrosis transmembrane conductance regulator (CFTR) plays an important role in normal MCC. TGF-β and CS (via TGF-β) promote acquired CFTR dysfunction by suppressing CFTR biogenesis and function. Understanding the mechanism by which CS promotes CFTR dysfunction can identify therapeutic leads to reverse CFTR suppression and rescue MCC. TGF-β alters the microRNAome of primary human bronchial epithelium. TGF-β and CS upregulate miR-145-5p expression to suppress CFTR and the CFTR modifier, SLC26A9. miR-145-5p upregulation with a concomitant CFTR and SLC26A9 suppression was validated in CS-exposed mouse models. While miR-145-5p antagonism rescued the effects of TGF-β in bronchial epithelial cells following transfection, an aptamer to block TGF-β signaling rescues CS- and TGF-β-mediated suppression of CFTR biogenesis and function in the absence of any transfection reagent. These results demonstrate that miR-145-5p plays a significant role in acquired CFTR dysfunction by CS, and they validate a clinically feasible strategy for delivery by inhalation to locally modulate TGF-β signaling in the airway and rescue CFTR biogenesis and function.
Childhood Adversity as a Plasticity Factor That Modifies the Association Between Subsequent Life Experience and Psychopathology
Authors: Erin C. Dunn
Journal: JAMA Network Open (2018)

Exposure to childhood adversity-whether poverty, maltreatment, or another life stressor-is one of the most potent social determinants of poor mental and physical health across the life span.From decades of research, it has been well established that childhood adversities at least double the risk of mental disorders that begin not only during childhood or adolescence, but even during adulthood.The consequences of childhood adversity on mental health are also transdiagnostic, spanning psychiatric diagnostic boundaries.Given these associations-and the fact that exposure to adversity and trauma is near ubiquitous worldwide-there is an urgent need to identify strategies to mitigate the negative consequences of adversity, in the service of ultimately preventing the onset of mental disorders and reducing their overall burden.
Eradication of Central Nervous System Leukemia of T-Cell Origin with a Brain-Permeable LSD1 Inhibitor
Authors: Shiori Saito, Jiro Kikuchi, Daisuke Koyama, Shin Sato, Hiroo Koyama, Naoki Osada, Yoshiaki Kuroda, Koshi Akahane, Takeshi Inukai, Takashi Umehara, Yusuke Furukawa
Journal: Clinical Cancer Research (2018)

Lysine-specific demethylase 1 (LSD1) regulates several biological processes via the bifunctional modulation of enhancer functions. Recently, we reported that LSD1 overexpression is a founder abnormality of T-cell leukemogenesis and is maintained in fully transformed T-cell acute lymphoblastic leukemia (T-ALL) cells. On the basis of this finding, we attempted to develop novel LSD1 inhibitors effective for T-ALL with central nervous system (CNS) involvement.We chemically modified the prototype LSD inhibitor tranylcypromine (TCP) and screened for cytotoxicity against TCP-resistant T-ALL cell lines. In vivo efficacy of novel LSD1 inhibitors was examined in immunodeficient mice transplanted with luciferase-expressing T-ALL cell lines, which faithfully reproduce human T-ALL with CNS involvement.We found robust cytotoxicity against T-ALL cells, but not normal bone marrow progenitors, for two N-alkylated TCP derivatives, S2116 and S2157. The two compounds induced apoptosis in TCP-resistant T-ALL cells in vitro and in vivo by repressing transcription of the NOTCH3 and TAL1 genes through increased H3K9 methylation and reciprocal H3K27 deacetylation at superenhancer regions. Both S2116 and S2157 significantly retarded the growth of T-ALL cells in xenotransplanted mice and prolonged the survival of recipients as monotherapy and in combination with dexamethasone. Notably, S2157 could almost completely eradicate CNS leukemia because of its ability to efficiently pass through the blood-brain barrier.These findings provide a molecular basis and rationale for the inclusion of a brain-permeable LSD1 inhibitor, S2157, in treatment strategies for T-ALL with CNS involvement.
Clinical Characteristics and Factors Associated With Mortality in First-Episode Infective Endocarditis Among Persons Who Inject Drugs
Authors: Laura Rodger, Stephannie Dresden Glockler-Lauf, Esfandiar Shojaei, Adeel Sherazi, Brian Hallam, Sharon Koivu, Kaveri Gupta, Seyed M. Hosseini-Moghaddam, Michael Silverman
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Persons who inject drugs (PWID) represent a distinct demographic of patients with infective endocarditis. Many centers do not perform valvular surgery on these patients owing to concerns about poor outcomes. Addiction services are underused in hospitals. <h3>Objectives</h3> To compare clinical characteristics in first-episode infective endocarditis in PWID who are surgically vs medically managed and to identify variables associated with mortality. <h3>Design, Setting, and Participants</h3> This case series studied PWID treated for a first episode of infective endocarditis between April 1, 2007, and March 30, 2016. Participants were adult patients (aged ≥18 years) admitted to any of 3 hospitals in London, Ontario, Canada. Analysis occurred between July 2016 and November 2017. <h3>Main Outcomes and Measures</h3> Survival among PWID; the causative organisms, site of infection, and cardiac as well as noncardiac complications; referral to addiction services; and surgical vs medical management. <h3>Results</h3> Of 370 total first-episode cases of infective endocarditis, 202 (54.6%) were in PWID. Among PWID, 105 (52%) were male, the median (interquartile range) age was 34 (28-42) years, and patients were predominantly positive for the hepatitis C virus (69.8% [141 of 202]). Right-sided infection was more common (61.4% [124 of 202]), and most infections were caused by<i>Staphylococcus aureus</i>(77.2% [156 of 202]). Surgery occurred in 19.3% of patients (39 of 202). The all-cause mortality rate was 33.7% (68 of 202). Adjusting for age and sex, survival analysis demonstrated that surgery was associated with lower mortality (hazard ratio [HR], 0.44; 95% CI, 0.23-0.84;<i>P</i> = .01), as was referral to addiction treatment (HR, 0.29; 95% CI, 0.12-0.73;<i>P</i> = .008). Higher mortality was associated with left-sided infection (HR, 3.26; 95% CI, 1.82-5.84;<i>P</i> &lt; .001) and bilateral involvement (HR, 4.51; 95% CI, 2.01-10.1;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> This study presents the demographic characteristics of first-episode infective endocarditis in PWID. Results highlight the potentially important role of addictions treatment in this population. Further study to optimize selection criteria for surgery in PWID is warranted.