tbuckley/cabot-search huggingface dataset:
Simple interventions to decrease use of chemotherapy in patients at the end of life.
Authors: Anne C. Chiang, Kerin B. Adelson, Jennifer Kapo, Kimberly M Severino, Rogerio Lilenbaum
Journal: Journal of Clinical Oncology (2018)

181 Background: Early palliative care referral has proven useful in reducing chemotherapy given to cancer patients in the last 30 days of life. We designed a program to help train primary oncologists in having goals of care (GOC) conversations with patients. We conducted this initiative across the Yale Cancer Center/Smilow Cancer Hospital Care Centers (SCHCCs). The aim was to determine whether simple tools could be used by general oncologists to improve patient care, as measured by chemotherapy utilization at the end of life. Methods: A multidisciplinary team completed process mapping and cause-and-effect barrier analysis regarding GOC discussion with patients. Five interventions (PDSA cycles) were chosen to improve physician skills with GOC conversations. SCHCC physicians (n = 21) utilized each tool on 5 patients per month from July to December 2017. Interventions included asking patients simple questions regarding GOC, using the phrase “allow natural death”, giving patients a “serious conversation starter kit”, and identifying patients with poor prognosis. A GOC survey was administered to physicians at baseline and after completion of the initiative. Data on chemotherapy and immunotherapy given during the last 30 days of life for SCHCC patients were measured. Results: SCHCC physicians who completed the baseline survey (n = 17) were 27% likely to discuss GOC repeatedly during the course of illness, compared to 70% post intervention (n = 10), while 88% felt comfortable discussing GOC at baseline compared to 100% after intervention. Chemotherapy within 30 days of death was administered to 30.3% patients (n = 109) in Q1 2017 and 23.3% in Q3 (n = 103) in the Care Centers. Of note, immunotherapy administered within 30 days of death was 6.4% in Q1 and 6.7% in Q3. Conclusions: A quality initiative focused on providing oncologists with simple tools to improve GOC conversations led to decrease from 30.3% to 23.3% of patients receiving chemotherapy within the last 30 days of life. Survey respondents felt more comfortable in discussing GOC and were more likely to do this throughout the course of illness. This pilot suggests that palliative care training of primary oncologists is feasible and may help to decrease unnecessary treatment at the end of life.
What interventions are effective to taper opioids in patients with chronic pain?
Authors: H Sandhu, M Underwood, AD Furlan, J Noyes, S Eldabe
Journal: BMJ (2018)

### What you need to know

Opioids are commonly prescribed for short term pain relief in people with chronic pain (not caused by cancer). If they are used long term, most patients develop tolerance, their pain increases, and clinicians gradually escalate the dose (fig 1). Sales of prescribed opioids in the USA quadrupled between 2000 and 2010.1 Media have reported the harms of dependence23 and the increasing number of deaths from accidental overdose.45678910 Other long term harms include immune suppression, hormonal imbalance, falls and fractures, acute myocardial infarction, addiction, sedation, and cognitive impairment.11



Fig 1 
Long term use of opioids leads to tolerance and increased levels of pain



There is very little guidance on withdrawing or tapering opioids in chronic pain (not caused by cancer). People can fear pain, withdrawal symptoms, a lack of social and healthcare support, and they may also distrust non-opioid methods of pain management.12 People may experience flu like symptoms, irritability, anxiety, nausea, diarrhoea, shivering, yawning, sweating, and altered sleep, generalised aches and pains, and abdominal cramps when they stop opioids.13 It is important to distinguish physical dependence on opioids (the physiological responses and symptoms above) from addiction (a compulsive need to take opioids for pleasure).14 Fewer than one in 30 …
Abstract 15453: HO-3867, a Peroxynitrite Scavenger, Ameliorates Progression of Pulmonary Hypertension Secondary to Left-Heart Failure through Restoration of PTEN activity
Authors: Yazhini Ravi, Shan K Naidu, Lucas A Citro, Balazs Bognor, Kalman Hideg, Chittoor B Sai-Sudhakar, Periannan Kuppusamy
Journal: Circulation (2012)

Pulmonary hypertension (PH), which develops secondary to left-heart failure (LHF), is a progressive disorder with high mortality and is a contra-indication for heart transplantation. Currently available therapies for PH are limited in scope. Recently, we observed significantly elevated levels of peroxynitrite (PN) in the lungs of rats subjected to LHF. PN induced smooth muscle cell (SMC) proliferation and pulmonary vascular remodeling by inactivating PTEN, a PI3K antagonist known to regulate cell proliferation. The study indicated that PN/PTEN could be used as a potential target for the management of LHF-PH. The goal of this study was to evaluate HO-3867, a dual-function antioxidant/antiproliferative agent, in ameliorating the progression of LHF-PH. In vitro studies established that HO-3867 is a potent scavenger of PN and is antiproliferative against PN-stimulated SMC proliferation (A). PH was induced by permanent ligation of LAD coronary artery in Sprague-Dawley rats for 4 weeks. Echo, hemodynamics, hist...
Combined use of Quantiferon and HBHA-based IGRA supports tuberculosis diagnosis and therapy management in children
Authors: Michela Sali, Danilo Buonsenso, Pamela D'Alfonso, Flavio De Maio, Manuela Ceccarelli, Basem Battah, Ivana Palucci, Teresa Chiacchio, Delia Goletti, Maurizio Sanguinetti, Piero Valentini, Giovanni Delogu
Journal: Journal of Infection (2018)
SP0073 Opioid prescribing: what’s the problem?
Authors: B.H. Smith
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Opioids have been used for at least 7,000 years in the treatment of acute pain, to aid sleep and to promote euphoria. Their short-term benefits are well-recognised, but longer-term benefits are less well understood and associated harms well-known. For pain lasting beyond the acute period, the prescribed use of strong opioids was, until recently, mainly restricted to cancer and palliative care, when life expectancy is limited. More recently, however, we have seen rapidly increasing use of both strong and weak opioids for chronic non-malignant pain. This has particularly been in North America where an “opioid epidemic” is apparent, but similar patterns are emerging across the world, including Europe. The commonest problems with long-term use of opioids include constipation, nausea and sedation. Other, perhaps more serious problems include hyperalgesia, endocrine and immune dysfunction, mood disorders, tolerance, addiction and death. Our systematic review estimated an incidence of iatrogenic misuse or addiction of ~4% among all people prescribed an opioid. The other problem is with the lack of high quality evidence to support their effectiveness in the long-term relief of pain, as we will hear later. These concerns have prompted the International Association for the Study of Pain to issue a recent carefully-worded statement on the use of opioids in chronic pain, advising caution and close monitoring. This presentation will summarise these issues, and present evidence of the increasing use of opioids in recent years, focusing on Europe and particularly Scotland, where prescribing rates rose 65% in a 10 year period. I will present evidence of both good and potentially harmful prescribing, evidence that most prescribing is “appropriate” in that it is associated with severe chronic pain, and, despite this, that a very large proportion of people with chronic pain are not prescribed any opioid. Opioids may still have a role in chronic non-malignant pain, but the goals of their use need to be increased function and improved quality of life, and we need careful selection of patients and evaluation of outcomes. <h3>Disclosure of Interest</h3> B. Smith Grant/research support from: Scottish Government, Chief Scientist Office
Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials
Authors: Nicolino Ruperto, Hermine I Brunner, Pierre Quartier, Tamàs Constantin, Nico M Wulffraat, Gerd Horneff, Ozgur Kasapcopur, Rayfel Schneider, Jordi Anton, Judith Barash, Reinhard Berner, Fabrizia Corona, Ruben Cuttica, Marine Fouillet-desjonqueres, Michel Fischbach, Helen E Foster, Dirk Foell, Sebastião C Radominski, Athimalaipet V Ramanan, Ralf Trauzeddel, Erbil Unsal, Jérémy Levy, Eleni Vritzali, Alberto Martini, Daniel J Lovell
Journal: Annals of the Rheumatic Diseases (2018)

Objectives To evaluate the long-term efficacy and safety of canakinumab in patients with active systemic juvenile idiopathic arthritis (JIA). Methods Patients (2–19 years) entered two phase III studies and continued in the long-term extension (LTE) study. Efficacy assessments were performed every 3 months, including adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR clinical remission on medication criteria (CR ACR ). Efficacy analyses are reported as per the intent-to-treat population. Results 144 of the 177 patients (81%) enrolled in the core study entered the LTE. Overall, 75 patients (42%) completed and 102 (58%) discontinued mainly for inefficacy (63/102, 62%), with higher discontinuation rates noted in the late responders group (n=25/31, 81%) versus early responders (n=11/38, 29%). At 2 years, aJIA-ACR 50/70/90 response rates were 62%, 61% and 54%, respectively. CR ACR was achieved by 20% of patients at month 6; 32% at 2 years. A JADAS low disease activity score was achieved by 49% of patients at 2 years. Efficacy results were maintained up to 5 years. Of the 128/177 (72.3%) patients on glucocorticoids, 20 (15.6%) discontinued and 28 (22%) tapered to 0.150 mg/kg/day. Seven patients discontinued canakinumab due to CR. There were 13 macrophage activation syndrome (three previously reported) and no additional deaths (three previously reported). No new safety findings were observed. Conclusion Response to canakinumab treatment was sustained and associated with substantial glucocorticoid dose reduction or discontinuation and a relatively low retention-on-treatment rate. No new safety findings were observed on long-term use of canakinumab. Trial registration numbers NCT00886769 , NCT00889863 , NCT00426218 and NCT00891046 .
A Convolutional Neural Network Uses Microscopic Images to Differentiate between Mouse and Human Cell Lines and Their Radioresistant Clones
Authors: Masayasu Toratani, Masamitsu Konno, Ayumu Asai, Jun Koseki, Koichi Kawamoto, Keisuke Tamari, Zhihao Li, Daisuke Sakai, Toshihiro Kudo, Taroh Satoh, Katsutoshi Sato, Daisuke Motooka, Daisuke Okuzaki, Yuichiro Doki, Masaki Mori, Kazuhiko Ogawa, Hideshi Ishii
Journal: Cancer Research (2018)

: Artificial intelligence (AI) trained with a convolutional neural network (CNN) is a recent technological advancement. Previously, several attempts have been made to train AI using medical images for clinical applications. However, whether AI can distinguish microscopic images of mammalian cells has remained debatable. This study assesses the accuracy of image recognition techniques using the CNN to identify microscopic images. We also attempted to distinguish between mouse and human cells and their radioresistant clones. We used phase-contrast microscopic images of radioresistant clones from two cell lines, mouse squamous cell carcinoma NR-S1, and human cervical carcinoma ME-180. We obtained 10,000 images of each of the parental NR-S1 and ME-180 controls as well as radioresistant clones. We trained the CNN called VGG16 using these images and obtained an accuracy of 96%. Features extracted by the trained CNN were plotted using t-distributed stochastic neighbor embedding, and images of each cell line were well clustered. Overall, these findings suggest the utility of image recognition using AI for predicting minute differences among phase-contrast microscopic images of cancer cells and their radioresistant clones. SIGNIFICANCE: This study demonstrates rapid and accurate identification of radioresistant tumor cells in culture using artifical intelligence; this should have applications in future preclinical cancer research.
Restructuring of inpatient rounds to improve quality of care in patients with cancer.
Authors: Devika Govind Das, Courtney Williams, Kelly Nicole Godby, Gabrielle Betty Rocque, Pamela Cargo, Kellie Flood
Journal: Journal of Clinical Oncology (2018)

232 Background: Traditionally, hospital units function as multidisciplinary teams which work in silos and communicate via notes in the Electronic Health System. This often leads to communication breakdown, frequently translating to adverse clinical outcomes and prolonged hospital length of stay. Our primary objective was to introduce Inter-Professional Team (IPT) rounds on the oncology unit and evaluate the impact on length of stay (LOS) within a Plan, Do, Study, Act (PDSA) cycle. Methods: The care transition team planned the IPT rounds structure and training curriculum which included team goals, post-rounds structure for addressing barriers to care progression, and member roles/scripting. Change in LOS and case mix index (CMI)-adjusted LOS post-IPT round implementation ( Do) in July 2017 was analyzed ( Study) using hierarchical linear models for patients with an admission to the oncology service from September 2016 to March 2018. Beta coefficients (β) and 95% confidence intervals (CI) were estimated and models were adjusted for calendar time. Results: Ten attending medical oncologists participated in IPT round implementation. Of 889 oncology admissions, median LOS and CMI-adjusted LOS pre-IPT round implementation (n = 464) was 4 days (IQR 2-6) and 3 days (IQR 1.8-4.7), while post-IPT round implementation (n = 425) was 4 days (IQR 2-6) and 2.9 days (IQR 1.9-4.4), respectively. Three common reasons for admission were septicemia (n = 96), hematologic complications (n = 42, e.g. anemia/neutropenia), and renal failure (n = 25). Adjusted models for LOS and CMI-adjusted LOS showed no significant difference post-IPT round implementation (β = 0.8 days, 95% CI -0.7-2.3; β = 0.5 days, 95% CI -0.3-1.3, respectively) when compared to pre-implementation. Conclusions: We did not observe decreased LOS in early outcomes. However, IDT rounds built on TEAMSTEPPS 2.0 elements with incorporation of key principles desirable in a patient care team. Next steps include further analysis to better understand cancer stages and diagnoses contributing to longer LOS. We also plan to evaluate patient satisfaction, educational needs, and readmission rates to restructure ( Act) IPT rounds to better serve the needs of our unique patient population.
HCCDB: A Database of Hepatocellular Carcinoma Expression Atlas
Authors: Qiuyu Lian, Shicheng Wang, Guchao Zhang, Dongfang Wang, Guijuan Luo, Jing Tang, Lei Chen, Jin Gu
Journal: Genomics Proteomics & Bioinformatics (2018)

Hepatocellular carcinoma (HCC) is highly heterogeneous in nature and has been one of the most common cancer types worldwide. To ensure repeatability of identified gene expression patterns and comprehensively annotate the transcriptomes of HCC, we carefully curated 15 public HCC expression datasets that cover around 4000 clinical samples and developed the database HCCDB to serve as a one-stop online resource for exploring HCC gene expression with user-friendly interfaces. The global differential gene expression landscape of HCC was established by analyzing the consistently differentially expressed genes across multiple datasets. Moreover, a 4D metric was proposed to fully characterize the expression pattern of each gene by integrating data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). To facilitate a comprehensive understanding of gene expression patterns in HCC, HCCDB also provides links to third-party databases on drug, proteomics, and literatures, and graphically displays the results from computational analyses, including differential expression analysis, tissue-specific and tumor-specific expression analysis, survival analysis, and co-expression analysis. HCCDB is freely accessible at http://lifeome.net/database/hccdb.
Optimizing the use of trimethoprim-sulfamethoxazole for prevention of PCP and opportunistic infections in allogeneic hematopoietic cell transplant recipients.
Authors: Emily Baneman, Nina Kim, Meenakshi Rana, Anne Sigrid Renteria, Amir S. Steinberg, Rita M. Jakubowski, Kendra Yum, Patricia Saunders, Samantha Jacobs
Journal: Journal of Clinical Oncology (2018)

138 Background: Trimethoprim-sulfamethoxazole (TMP-SMX) is preferred for prevention of Pneumocystis pneumonia (PCP), toxoplasmosis and other opportunistic infections after allogeneic hematopoietic cell transplantation (HCT), but it is often withheld due to potential adverse events (AE). From July 2016-June 2017 we observed that 31% of allogeneic HCT recipients at our hospital were prescribed TMP-SMX throughout the high risk period (day +30-180). Therefore, we developed an intervention to explore reasons for such a low prescription rate and to optimize TMP-SMX use. Methods: Our institution’s HCT practice guidelines were revised to include indications for TMP-SMX and alternative agents for PCP and Toxoplasma prophylaxis and specific clinical and laboratory criteria for withholding TMP-SMX. Education on the guidelines was provided to transplant clinicians. Outpatient encounters were prospectively audited from January to April 2018. Providers received real-time feedback with recommendations in accordance with our guidelines prior to patients’ visits. Results: We reviewed 321 outpatient encounters among 112 patients. Seventy-six (68%) patients were on TMP-SMX prophylaxis at the first reviewed encounter. Cytopenias were the most common reason for withholding TMP-SMX, occurring in 50 (57%) encounters, followed by elevated liver function tests (LFTs) (13.6%), hyperkalemia (3.4%), elevated creatinine (3.4%), rash or hypersensitivity (3.4%), and unknown/other (22%) . In 73 encounters in which patients received alternative or no PCP prophylaxis, we recommended changing to TMP-SMX. This intervention was accepted in 15 patients, 11(73%) of whom tolerated TMP-SMX well. In the remaining four patients, TMP-SMX was subsequently discontinued due to unrelated AE (N = 3) and possible TMP-SMX-associated elevated LFTs (N = 1). Conclusions: Provider education and real-time feedback led to increased utilization of TMP-SMX for prevention of PCP and other opportunistic infections in HCT recipients without an increase in TMP-SMX-related adverse effects. Further study is needed to understand the low clinician acceptance rate of the intervention.
Protein Nanotherapeutics as an Emerging Modality for Cancer Therapy
Authors: Liang Cheng, Liang Yang, Fenghua Meng, Zhiyuan Zhong
Journal: Advanced Healthcare Materials (2018)

Abstract Protein drugs are a unique and versatile class of biotherapeutics that have not only high biological activity but also superb specificity. This rapidly evolving biotechnology has rendered it possible to produce various proteins in a large scale and reproducible way. Many proteins have demonstrated striking anticancer activities and have emerged as advanced alternatives to cytotoxic chemotherapeutic agents for cancer therapy. The clinical translation of anticancer proteins with intracellular targets is, nevertheless, severely hindered by their fast degradation in vivo, poor cell penetration, and inefficient intracellular transportation. The past few years have witnessed tremendous effort and progress in developing polymeric protein delivery nanosystems, ranging from nanoparticles, nanocapsules, nanogels, micelles, to polymersomes, for the treatment of different tumors such as lung tumors, breast tumors, ovarian cancers, and glioblastoma. These proof‐of‐concept studies point out that protein nanotherapeutics, with rationally designed nanovehicles, are able to overcome the extracellular barriers, cell membrane barriers, and intracellular barriers, and systemically deliver proteins into targeted cancer cells, resulting in effective cancer protein therapy. Protein nanotherapeutics appear to be a novel modality for safe and efficient cancer treatment.
First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes
Authors: Diana L. Cousminer, Emma Ahlqvist, Rajashree Mishra, Mette K. Andersen, Alessandra Chesi, Mohammad I. Hawa, Asa Davis, Kenyaita M. Hodge, Jonathan P. Bradfield, Kaixin Zhou, Vanessa C. Guy, Mikael Åkerlund, Mette Wod, Lars G. Fritsche, Henrik Vestergaard, James Snyder, Kurt Højlund, Allan Linneberg, Annemari Käräjämäki, Ivan Brandslund, Cecilia E. Kim, Daniel Witte, Elin Pettersen Sørgjerd, David J. Brillon, Oluf Pedersen, Henning Beck-Nielsen, Niels Grarup, Richard E. Pratley, Michael R. Rickels, Adrian Vella, Fernando Ovalle, Olle Melander, Ronald I. Harris, Stephen Varvel, Valdemar E.R. Grill, Hakon Hakonarson, Philippe Froguel, John T. Lonsdale, Didac Mauricio, Nanette C. Schloot, Kamlesh Khunti, Carla J. Greenbaum, Bjørn Olav Åsvold, Knud B. Yderstræde, Ewan R. Pearson, Stanley Schwartz, Benjamin F. Voight, Torben Hansen, Tiinamaija Tuomi, Bernhard O. Boehm, Leif Groop, R. David Leslie, Struan F.A. Grant, Shana E. McCormack, Jonathan A. Mitchell, Andrea Kelly, Heidi J. Kalkwarf, Joan M. Lappe, John A. Shepherd, Sharon E. Oberfield, Vicente Gilsanz, Babette S. Zemel
Journal: Diabetes Care (2018)

OBJECTIVE Latent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype. RESEARCH DESIGN AND METHODS We performed the first genome-wide association study of LADA in case subjects of European ancestry versus population control subjects (n = 2,634 vs. 5,947) and compared against both case subjects with type 1 diabetes (n = 2,454 vs. 968) and type 2 diabetes (n = 2,779 vs. 10,396). RESULTS The leading genetic signals were principally shared with type 1 diabetes, although we observed positive genetic correlations genome-wide with both type 1 and type 2 diabetes. Additionally, we observed a novel independent signal at the known type 1 diabetes locus harboring PFKFB3, encoding a regulator of glycolysis and insulin signaling in type 2 diabetes and inflammation and autophagy in autoimmune disease, as well as an attenuation of key type 1–associated HLA haplotype frequencies in LADA, suggesting that these are factors that distinguish childhood-onset type 1 diabetes from adult autoimmune diabetes. CONCLUSIONS Our results support the need for further investigations of the genetic factors that distinguish forms of autoimmune diabetes as well as more precise classification strategies.