tbuckley/cabot-search huggingface dataset:
Redesigning healthcare to fit with people
Authors: Kim Erwin, Jerry A Krishnan
Journal: BMJ (2016)

Design expertise can improve delivery of care

Healthcare expenditures vary fourfold across the globe, from less than 5% to nearly 20% of a nation’s gross domestic product.1 Higher levels of spending, however, have not necessarily produced better results, suggesting that some healthcare systems are more efficient than others.2 These observations have led to various efforts to improve the efficiency of care systems.

In Europe and the US, for example, emphasis is increasingly shifting away from the “volume” of care (number of services) to the “value” of care (quality, outcomes, and costs).3 4 Government and other payers are driving health systems to invest in electronic health records, data analytics, performance improvement, and clinical decision support tools. Unfortunately, these investments are often launched as a series of individual fixes targeting different types of apparent underuse, overuse, or misuse of healthcare, disconnected from each other and from workflows in clinical settings. And thus well intentioned reforms are …
NIV for OHS without severe OSAS: is it worth it?
Authors: P B Murphy, J-P Janssens
Journal: Thorax (2016)

Home non-invasive ventilation (NIV) has been used to manage chronic respiratory failure since the polio epidemics of the 1940s; however, the support for many of the indications remains based on small non-randomised or uncontrolled studies. Obesity hypoventilation syndrome (OHS) is an increasingly common cause of chronic respiratory failure and indication for home mechanical ventilation; unsurprisingly as the diagnosis remains frequently missed, significant variation exists across Europe.1 ,2 The majority of patients with OHS have significant obstructive sleep apnoea (OSA) and recent data have demonstrated the benefits of NIV in a randomised controlled trial.3 ,4 However, it has been increasingly clear that the clinical description which was first reported over 60 years ago5 is in fact made up of distinct clinical phenotypes, most frequently divided by the nature of the sleep-disordered breathing, which is driving respiratory failure.6 In fact, the broad definition is being challenged further with suggestions to incorporate base excess rather than arterial carbon dioxide in the diagnostic criteria and to consider daytime normocapnic subjects with a base excess ≥2 mmol/L as having an early obesity-related nocturnal hypoventilation.7 Analogous to the phenotypes being increasingly advocated in COPD,8 the subdivisions of OHS may have different risk profiles and require differing treatment strategies.

Masa et al 9 present data in this edition of Thorax on …
Optical Coherence Tomography to Optimize Results of Percutaneous Coronary Intervention in Patients with Non–ST-Elevation Acute Coronary Syndrome
Authors: Nicolas Meneveau, Geraud Souteyrand, Pascal Motreff, Christophe Caussin, Nicolas Amabile, Patrick Ohlmann, Olivier Morel, Yoann Lefrançois, Vincent Descotes-Genon, Johanne Silvain, Nassim Braik, Romain Chopard, Marion Chatot, Fiona Ecarnot, Hélène Tauzin, Eric Van Belle, Loïc Belle, François Schiele
Journal: Circulation (2016)

No randomized study has investigated the value of optical coherence tomography (OCT) in optimizing the results of percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndromes.We conducted a multicenter, randomized study involving 240 patients with non-ST-segment elevation acute coronary syndromes to compare OCT-guided PCI (use of OCT pre- and post-PCI; OCT-guided group) to fluoroscopy-guided PCI (angiography-guided group). The primary end point was the functional result of PCI assessed by the measure of post PCI fractional flow reserve. Secondary end points included procedural complications and type 4a periprocedural myocardial infarction. Safety was assessed by the rate of acute kidney injury.OCT use led to a change in procedural strategy in 50% of the patients in the OCT-guided group. The primary end point was improved in the OCT-guided group, with a significantly higher fractional flow reserve value (0.94±0.04 versus 0.92±0.05, P=0.005) compared with the angiography-guided group. There was no significant difference in the rate of type 4a myocardial infarction (33% in the OCT-group versus 40% in the angiography-guided group, P=0.28). The rates of procedural complications (5.8%) and acute kidney injury (1.6%) were identical in each group despite longer procedure time and use of more contrast medium in the OCT-guided group. Post-PCI OCT revealed stent underexpansion in 42% of patients, stent malapposition in 32%, incomplete lesion coverage in 20%, and edge dissection in 37.5%. This led to the more frequent use of poststent overdilation in the OCT-guided group versus the angiography-guided group (43% versus 12.5%, P<0.0001) with lower residual stenosis (7.0±4.3% versus 8.7±6.3%, P=0.01).In patients with non-ST-segment elevation acute coronary syndromes, OCT-guided PCI is associated with higher postprocedure fractional flow reserve than PCI guided by angiography alone. OCT did not increase periprocedural complications, type 4a myocardial infarction, or acute kidney injury.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01743274.
Oxygen-Boosted Chemotherapy: Oxygen Nanocarrier for Combined Cancer Therapy: Oxygen-Boosted ATP-Responsive Chemotherapy with Amplified ROS Lethality (Adv. Healthcare Mater. 17/2016)
Authors: Pengfei Zhao, Mingbin Zheng, Zhenyu Luo, Xiujun Fan, Zonghai Sheng, Ping Gong, Ze Chen, Baozhen Zhang, Dapeng Ni, Yifan Ma, Lintao Cai
Journal: Advanced Healthcare Materials (2016)

An oxygen nanocarrier (A/D-ONC) absorbing doxorubicin-intercalated DNA duplex is developed by Jin Chang, Nan Ma, Rainer Haag and co-workers on page 2161. After cell endocytosis, oxygenated A/D-ONC donates O2 to cancer cells for therapy by two ways: 1) increase intracellular ATP content to promote ATP-responsive DOX release for chemotherapy, converting ATP to the activator of detrimental chemotherapy; 2) synchronously increase reactive oxygen species (ROS) amount to amplify the lethality to cancer cells.
Class I PI3K Isoforms Exert a Differential Role On Survival and Cell Trafficking In Multiple Myeloma
Authors: Ilyas Sahin, Feda Azab, Michele Moschetta, Yuji Mishima, Brian Tsang, Patricia Maiso, Antonio Sacco, Aldo M Roccaro, Abdel Kareem Azab, Irene M. Ghobrial
Journal: Blood (2013)
Society of Surgical Oncology–American Society for Radiation Oncology–American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ
Authors: Monica Morrow, Kimberly J. Van Zee, Lawrence J. Solin, Nehmat Houssami, Mariana Chavez-MacGregor, Jay R. Harris, Janet Horton, Shelley Hwang, Peggy L. Johnson, M. Luke Marinovich, Stuart J. Schnitt, Irene Wapnir, Meena S. Moran
Journal: Journal of Clinical Oncology (2016)

Background Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation (WBRT). Methods A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus. Results Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2 mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2 mm margins. Negative margins less than 2 mm alone are not an indication for mastectomy, and factors known to impact rates of IBTR should be considered in determining the need for re-excision. Conclusion The use of a 2 mm margin as the standard for an adequate margin in DCIS treated with WBRT is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcome, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins < 2 mm.
Exportin-5 Functions as an Oncogene and a Potential Therapeutic Target in Colorectal Cancer
Authors: Kunitoshi Shigeyasu, Yoshinaga Okugawa, Shusuke Toden, C. Richard Boland, Ajay Goel
Journal: Clinical Cancer Research (2016)

Purpose: Dysregulated expression of miRNAs has emerged as a hallmark feature in human cancers. Exportin-5 (XPO5), a karyopherin family member, is a key protein responsible for transporting precursor miRNAs from the nucleus to the cytoplasm. Although XPO5 is one of the key regulators of miRNA biogenesis, its functional role and potential clinical significance in colorectal cancer remains unclear.Experimental Design: The expression levels of XPO5 were initially assessed in three genomic datasets, followed by determination and validation of the relationship between XPO5 expression and clinicopathologic features in two independent colorectal cancer patient cohorts. A functional characterization of XPO5 in colorectal cancer was examined by targeted gene silencing in colorectal cancer cell lines and a xenograft animal model.Results: XPO5 is upregulated, both at mRNA and protein levels, in colorectal cancers compared with normal tissues. High XPO5 expression is associated with worse clinicopathologic features and poor survival in colorectal cancer patient cohorts. The siRNA knockdown of XPO5 resulted in reduced cellular proliferation, attenuated invasion, induction of G1-S cell-cycle arrest, and downregulation of key oncogenic miRNAs in colorectal cancer cells. These findings were confirmed in a xenograft animal model, wherein silencing of XPO5 resulted in the attenuation of tumor growth.Conclusions: XPO5 acts like an oncogene in colorectal cancer by regulating the expression of miRNAs and may be a potential therapeutic target in colorectal cancer. Clin Cancer Res; 23(5); 1312-22. ©2016 AACR.
Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus (RAPS): a randomised, controlled, open-label, phase 2/3, non-inferiority trial
Authors: Hannah Cohen, Beverley J Hunt, Maria Efthymiou, Deepa R J Arachchillage, Ian J Mackie, Simon Clawson, Yvonne Sylvestre, Samuel J Machin, Maria L Bertolaccini, Maria Ruiz-Castellano, Nicola Muirhead, Caroline J Doré, Munther Khamashta, David A Isenberg
Journal: The Lancet Haematology (2016)

Rivaroxaban is established for the treatment and secondary prevention of venous thromboembolism, but whether it is useful in patients with antiphospholipid syndrome is uncertain.This randomised, controlled, open-label, phase 2/3, non-inferiority trial, done in two UK hospitals, included patients with antiphospholipid syndrome who were taking warfarin for previous venous thromboembolism, with a target international normalised ratio of 2·5. Patients were randomly assigned 1:1 to continue with warfarin or receive 20 mg oral rivaroxaban daily. Randomisation was done centrally, stratified by centre and patient type (with vs without systemic lupus erythematosus). The primary outcome was percentage change in endogenous thrombin potential (ETP) from randomisation to day 42, with non-inferiority set at less than 20% difference from warfarin in mean percentage change. Analysis was by modified intention to treat. Other thrombin generation parameters, thrombosis, and bleeding were also assessed. Treatment effect was measured as the ratio of rivaroxaban to warfarin for thrombin generation. This trial is registered with the ISRCTN registry, number ISRCTN68222801.Of 116 patients randomised between June 5, 2013, and Nov 11, 2014, 54 who received rivaroxaban and 56 who received warfarin were assessed. At day 42, ETP was higher in the rivaroxaban than in the warfarin group (geometric mean 1086 nmol/L per min, 95% CI 957-1233 vs 548, 484-621, treatment effect 2·0, 95% CI 1·7-2·4, p<0·0001). Peak thrombin generation was lower in the rivaroxaban group (56 nmol/L, 95% CI 47-66 vs 86 nmol/L, 72-102, treatment effect 0·6, 95% CI 0·5-0·8, p=0·0006). No thrombosis or major bleeding were seen. Serious adverse events occurred in four patients in each group.ETP for rivaroxaban did not reach the non-inferiority threshold, but as there was no increase in thrombotic risk compared with standard-intensity warfarin, this drug could be an effective and safe alternative in patients with antiphospholipid syndrome and previous venous thromboembolism.Arthritis Research UK, Comprehensive Clinical Trials Unit at UCL, LUPUS UK, Bayer, National Institute for Health Research Biomedical Research Centre.
Neural reuse leads to associative connections between concrete (physical) and abstract (social) concepts and motives
Authors: Yimeng Wang, John A Bargh
Journal: Behavioral and Brain Sciences (2016)

Consistent with neural reuse theory, empirical tests of the related "scaffolding" principle of abstract concept development show that higher-level concepts "reuse" and are built upon fundamental motives such as survival, safety, and consumption. This produces mutual influence between the two levels, with far-ranging impacts from consumer behavior to political attitudes.
Mutations In MLL2 and MEF2B Genes In Follicular Lymphoma and Diffuse Large B-Cell Lymphoma
Authors: Maria Mendez-Lago, Ryan D Morin, Andrew J Mungall, Susanna Chan, Suganthi Chittaranjan, Tesa Severson, Rodrigo Goya, Karen Mungall, Nathalie A Johnson, Merrill Boyle, Bruce Woolcock, Thomas Zeng, Helen McDonald, Jianghong An, Oleksandr Yakovenko, Angela Tam, Yongjun Zhao, Martin Hirst, Richard Moore, Jacqueline E Schein, Steven J Jones, Douglas E Horsman, Randy D. Gascoyne, Joseph M. Connors, Marco A Marra
Journal: Blood (2010)
Acute Cholangitis Management
Authors: Kenric M. Murayama
Journal: JAMA Surgery (2016)

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Authors: Muthiah Vaduganathan, Deepak L. Bhatt, Byron L. Cryer, Yuyin Liu, Wen-Hua Hsieh, Gheorghe Doros, Marc Cohen, Angel Lanas, Thomas J. Schnitzer, Thomas L. Shook, Pablo Lapuerta, Mark A. Goldsmith, Loren Laine, Christopher P. Cannon
Journal: Journal of the American College of Cardiology (2016)
NICE recommends 3D heart imaging for diagnosing heart disease
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

Medical software that helps doctors visualise the blood vessels in the heart without invasive tests could help to diagnose heart conditions in patients with chest pain and suspected angina, the National Institute for Health and Care Excellence (NICE) has said.

NICE says that 36 000 people in England could benefit from the new technology every year, saving the NHS around £7.7m (€9m; $10.2m) by avoiding some invasive investigations and …
Evofosfamide (TH-302) in combination with gemcitabine in previously untreated patients with metastatic or locally advanced unresectable pancreatic ductal adenocarcinoma: Primary analysis of the randomized, double-blind phase III MAESTRO study.
Authors: Eric Van Cutsem, Heinz-Josef Lenz, Junji Furuse, Josep Tabernero, Volker Heinemann, Tatsuya Ioka, Igor Bazin, Makoto Ueno, Tibor Csõszi, Harpreet Wasan, Bohuslav Melichar, Petr Karasek, Teresa Macarulla, Carmen Guillén Ponce, Ewa Kalinka-Warzocha, Zsolt Horvath, Hans Prenen, Michael Schlichting, Fazal Mehdi, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2016)

193 Background: Pancreatic ductal adenocarcinoma (PDAC) is invariably diagnosed at an advanced stage and has poor clinical outcome. Hypoxia is a significant prognostic factor in PDAC progression and is associated with poor prognosis. Evofosfamide (Evo, previously known as TH-302) is a hypoxia-activated prodrug of bromo-isophosphoramide mustard (Br-IPM) that is preferentially activated under hypoxic conditions. The addition of Evo to gemcitabine (Gem) significantly improved progression-free survival (PFS) in a randomized phase II trial in advanced PDAC (NCT01144455). Methods: MAESTRO is an international, randomized, double-blind, placebo-controlled phase III trial of Evo/Gem vs Placebo/Gem in patients (pts) with measurable, locally advanced unresectable or metastatic PDAC (NCT01746979). Evo and Gem were administered intravenously at a dose of 340 mg/m 2 and 1,000 mg/m 2 , respectively, on days 1, 8, and 15 of a 28-day cycle. Treatment continued until disease progression. Key eligibility criteria included ECOG PS 0/1 and no neoadjuvant or adjuvant chemotherapy &lt;6 months prior to entry. The primary endpoint was overall survival (OS) with the study designed to detect a HR of 0.75 with 90% power. Secondary endpoints included PFS and objective response rate (ORR), employing a hierarchical testing procedure with a 2-sided α=0.05 at each level. Results: A total of 693 pts were randomized to treatment with Evo/Gem (n=xxx) or Placebo/Gem (n=yyy). Baseline pt characteristics were similar between treatment arms. The OS HR was X.XX (95% CI: Y.YY, Z.ZZ; p=A.AAA). Median OS was AA.A months (m) for Evo/Gem vs BB.B m for Placebo/Gem. Median PFS was C.C m and D.D m, respectively (HR E.EE [95% CI: F.FF, G.GG; p = H.HHH). ORR was JJ.J% with Evo/Gem vs KK.K% with Placebo/Gem (p = L.LLL). Grade ≥3 adverse events (AEs) occurring in &gt;5% of pts in treated with Evo/Gem were: TBC. Conclusions: The data from the MAESTRO trial will make an important contribution to our understanding of PDAC treatment. Clinical trial information: NCT01746979.
ELOQUENT-2: A phase III, randomized, open-label trial of lenalidomide/dexamethasone (Len/Dex) with or without elotuzumab (Elo) in relapsed or refractory multiple myeloma (RR MM) (CA204-004).
Authors: Sagar Lonial, Paul Gerard Guy Richardson, Philippe Moreau, Robert Z. Orlowski, Jesùs F. San-Miguel, Meletios A. Dimopoulos, Antonio Pierangelo Palumbo, Thierry Facon, Ravi Vij, Darrell White, Donna Ellen Reece, Anil Singhal, Glenn Scott Kroog, Justin Kopit, Kenneth Carl Anderson
Journal: Journal of Clinical Oncology (2012)

TPS8112 Background: MM remains incurable and patients (pts) typically relapse or become refractory to current treatments. Novel regimens are needed to improve pt outcomes. Elo is a humanized monoclonal IgG1 antibody targeting the cell surface glycoprotein CS1, which is highly expressed on &gt;95% of MM cells. Len/Dex is approved for treatment of relapsed MM and an objective response rate (ORR) of ~60% was reported in phase III trials of this combination in RR MM. In a phase II study (N=73) of Elo (10 or 20 mg/kg) in combination with Len/Dex in pts with RR MM, the 10 mg/kg group (n=36) demonstrated an ORR of 92% and median progression-free survival (PFS) that was not reached after a median follow-up of 14.1 months. Encouraging activity was seen in patients with high-risk cytogenetics and/or stage 2-3 disease. Based on these data, a randomized, open-label phase III trial has been initiated to determine if the addition of Elo to Len/Dex will improve PFS in patients with RR MM compared with Len/Dex alone. Methods: Pts (N=640) with RR MM and 1-3 prior therapies are eligible, including pts with mild or moderate renal impairment. Pts are randomized in a 1:1 ratio to receive 28-day cycles of Len 25 mg PO (days 1-21) and Dex 40 mg PO (days 1, 8, 15 and 22) with or without Elo. Elo dose and schedule is 10 mg/kg IV on days 1, 8, 15, 22 in the first 2 cycles and on days 1 and 15 in subsequent cycles. Dex 8 mg IV + 28 mg PO is used during the weeks with Elo. Treatment will continue until disease progression, death, or withdrawal of consent. Patients will be followed for tumor response every 4 weeks until progressive disease and then survival every 12 weeks. The primary endpoint is PFS (90% power for a hazard ratio [experimental to control arm] of 0.74) and the secondary endpoints are ORR and overall survival. Exploratory endpoints are safety, time to response, duration of response, time to subsequent therapy, health-related quality of life, and pharmacokinetics and immunogenicity of Elo. Potential biomarkers will also be assessed. As of January 10th, 2012, 107 pts were enrolled and 68 pts were treated. NCT01239797.
The ERS-endorsed official ATS/CDC/IDSA clinical practice guidelines on treatment of drug-susceptible tuberculosis
Authors: Giovanni Sotgiu, Payam Nahid, Robert Loddenkemper, Ibrahim Abubakar, Marc Miravitlles, Giovanni Battista Migliori
Journal: European Respiratory Journal (2016)

The World Health Organization (WHO) estimates that 9.6 million cases of tuberculosis (TB) occurred in 2014 (corresponding to 133 cases per 100 000 population) with 1.5 million deaths [1]. Furthermore, 3.3% of new and 20% of previously treated cases harbour multidrug-resistant (MDR)-TB strains. Eastern European and central Asian countries still have the highest prevalence of MDR-TB. In low TB incidence countries (largely covering North America and Western Europe; figure 1) 155 000 TB cases occur every year with over 10 000 deaths [2]. Updated clinical practice guidelines on TB treatment provide clinical and public health management recommendations <http://ow.ly/FDcN302Jdmp> The authors wish to thank Rosella Centis and Lia D'Ambrosio, WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy for their useful comments and for the editorial support in finalising the manuscript.
Urea impairs β cell glycolysis and insulin secretion in chronic kidney disease
Authors: Laetitia Koppe, Elsa Nyam, Kevin Vivot, Jocelyn E. Manning Fox, Xiao-Qing Dai, Bich N. Nguyen, Dominique Trudel, Camille Attané, Valentine S. Moullé, Patrick E. MacDonald, Julien Ghislain, Vincent Poitout
Journal: Journal of Clinical Investigation (2016)

Disorders of glucose homeostasis are common in chronic kidney disease (CKD) and are associated with increased mortality, but the mechanisms of impaired insulin secretion in this disease remain unclear. Here, we tested the hypothesis that defective insulin secretion in CKD is caused by a direct effect of urea on pancreatic β cells. In a murine model in which CKD is induced by 5/6 nephrectomy (CKD mice), we observed defects in glucose-stimulated insulin secretion in vivo and in isolated islets. Similarly, insulin secretion was impaired in normal mouse and human islets that were cultured with disease-relevant concentrations of urea and in islets from normal mice treated orally with urea for 3 weeks. In CKD mouse islets as well as urea-exposed normal islets, we observed an increase in oxidative stress and protein O-GlcNAcylation. Protein O-GlcNAcylation was also observed in pancreatic sections from CKD patients. Impairment of insulin secretion in both CKD mouse and urea-exposed islets was associated with reduced glucose utilization and activity of phosphofructokinase 1 (PFK-1), which could be reversed by inhibiting O-GlcNAcylation. Inhibition of O-GlcNAcylation also restored insulin secretion in both mouse models. These results suggest that insulin secretory defects associated with CKD arise from elevated circulating levels of urea that increase islet protein O-GlcNAcylation and impair glycolysis.