tbuckley/cabot-search huggingface dataset:
Associations Between Asthma Severity and Responsiveness to Th2- and Th17-derived Cytokines in Pediatric Asthmatics
Authors: Jaclyn W. McAlees, Theresa Baker, Sara L. Hall, Emily Kim, Christopher G. McKnight, Andrew Warren Lindsley, Richard Thomas Strait, Xue Zhang, Jocelyn M. Biagini Myers, Melinda Butsch Kovacic, Ian Paul Lewkowich
Journal: Journal of Allergy and Clinical Immunology (2018)
Administrative Costs Associated With Physician Billing and Insurance-Related Activities at an Academic Health Care System
Authors: Phillip Tseng, Robert S. Kaplan, Barak D. Richman, Mahek A. Shah, Kevin A. Schulman
Journal: JAMA (2018)

<h3>Importance</h3> Administrative costs in the US health care system are an important component of total health care spending, and a substantial proportion of these costs are attributable to billing and insurance-related activities. <h3>Objective</h3> To examine and estimate the administrative costs associated with physician billing activities in a large academic health care system with a certified electronic health record system. <h3>Design, Setting, and Participants</h3> This study used time-driven activity-based costing. Interviews were conducted with 27 health system administrators and 34 physicians in 2016 and 2017 to construct a process map charting the path of an insurance claim through the revenue cycle management process. These data were used to calculate the cost for each major billing and insurance-related activity and were aggregated to estimate the health system's total cost of processing an insurance claim. <h3>Exposures</h3> Estimated time required to perform billing and insurance-related activities, based on interviews with management personnel and physicians. <h3>Main Outcomes and Measures</h3> Estimated billing and insurance-related costs for 5 types of patient encounters: primary care visits, discharged emergency department visits, general medicine inpatient stays, ambulatory surgical procedures, and inpatient surgical procedures. <h3>Results</h3> Estimated processing time and total costs for billing and insurance-related activities were 13 minutes and $20.49 for a primary care visit, 32 minutes and $61.54 for a discharged emergency department visit, 73 minutes and $124.26 for a general inpatient stay, 75 minutes and $170.40 for an ambulatory surgical procedure, and 100 minutes and $215.10 for an inpatient surgical procedure. Of these totals, time and costs for activities carried out by physicians were estimated at a median of 3 minutes or $6.36 for a primary care visit, 3 minutes or $10.97 for an emergency department visit, 5 minutes or $13.29 for a general inpatient stay, 15 minutes or $51.20 for an ambulatory surgical procedure, and 15 minutes or $51.20 for an inpatient surgical procedure. Of professional revenue, professional billing costs were estimated to represent 14.5% for primary care visits, 25.2% for emergency department visits, 8.0% for general medicine inpatient stays, 13.4% for ambulatory surgical procedures, and 3.1% for inpatient surgical procedures. <h3>Conclusions and Relevance</h3> In a time-driven activity-based costing study in a large academic health care system with a certified electronic health record system, the estimated costs of billing and insurance-related activities ranged from $20 for a primary care visit to $215 for an inpatient surgical procedure. Knowledge of how specific billing and insurance-related activities contribute to administrative costs may help inform policy solutions to reduce these expenses.
Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty
Authors: David R. Anderson, Michael Dunbar, John Murnaghan, Susan R. Kahn, Peter Gross, Michael Forsythe, Stephane Pelet, William Fisher, Etienne Belzile, Sean Dolan, Mark Crowther, Eric Bohm, Steven J. MacDonald, Wade Gofton, Paul Kim, David Zukor, Susan Pleasance, Pantelis Andreou, Steve Doucette, Chris Theriault, Abongnwen Abianui, Marc Carrier, Michael J. Kovacs, Marc A. Rodger, Doug Coyle, Philip S. Wells, Pascal-Andre Vendittoli
Journal: New England Journal of Medicine (2018)

Clinical trials and meta-analyses have suggested that aspirin may be effective for the prevention of venous thromboembolism (proximal deep-vein thrombosis or pulmonary embolism) after total hip or total knee arthroplasty, but comparisons with direct oral anticoagulants are lacking for prophylaxis beyond hospital discharge.
Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial
Authors: Ianthe Boden, Elizabeth H Skinner, Laura Browning, Julie Reeve, Lesley Anderson, Cat Hill, Iain K Robertson, David Story, Linda Denehy
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To assess the efficacy of a single preoperative physiotherapy session to reduce postoperative pulmonary complications (PPCs) after upper abdominal surgery. <h3>Design</h3> Prospective, pragmatic, multicentre, patient and assessor blinded, parallel group, randomised placebo controlled superiority trial. <h3>Setting</h3> Multidisciplinary preadmission clinics at three tertiary public hospitals in Australia and New Zealand. <h3>Participants</h3> 441 adults aged 18 years or older who were within six weeks of elective major open upper abdominal surgery were randomly assigned through concealed allocation to receive either an information booklet (n=219; control) or preoperative physiotherapy (n=222; intervention) and followed for 12 months. 432 completed the trial. <h3>Interventions</h3> Preoperatively, participants received an information booklet (control) or an additional 30 minute physiotherapy education and breathing exercise training session (intervention). Education focused on PPCs and their prevention through early ambulation and self directed breathing exercises to be initiated immediately on regaining consciousness after surgery. Postoperatively, all participants received standardised early ambulation, and no additional respiratory physiotherapy was provided. <h3>Main outcome measures</h3> The primary outcome was a PPC within 14 postoperative hospital days assessed daily using the Melbourne group score. Secondary outcomes were hospital acquired pneumonia, length of hospital stay, utilisation of intensive care unit services, and hospital costs. Patient reported health related quality of life, physical function, and post-discharge complications were measured at six weeks, and all cause mortality was measured to 12 months. <h3>Results</h3> The incidence of PPCs within 14 postoperative hospital days, including hospital acquired pneumonia, was halved (adjusted hazard ratio 0.48, 95% confidence interval 0.30 to 0.75, P=0.001) in the intervention group compared with the control group, with an absolute risk reduction of 15% (95% confidence interval 7% to 22%) and a number needed to treat of 7 (95% confidence interval 5 to 14). No significant differences in other secondary outcomes were detected. <h3>Conclusion</h3> In a general population of patients listed for elective upper abdominal surgery, a 30 minute preoperative physiotherapy session provided within existing hospital multidisciplinary preadmission clinics halves the incidence of PPCs and specifically hospital acquired pneumonia. Further research is required to investigate benefits to mortality and length of stay. <h3>Trial registration</h3> Australian New Zealand Clinical Trials Registry ANZCTR 12613000664741.
Mise en place de fiduciels intra prostatiques par échoendoscopie sans anesthésie générale. Première expérience
Authors: JM Samson, M Edouard, G Coraggio, A Bossi, R Bou-Farah, P Burtin
Journal: Endoscopy (2018)

Afin de maximiser le traitement et de réduire sa toxicité, la radiothérapie du cancer de prostate nécessite la mise en place de fiduciels avec des systèmes dédiés, nécessitant une anesthésie générale.
Abstract #3863: Derivatives of seliciclib with improved potency both in vitro and in vivo as novel cyclin dependent kinase (CDK) inhibitors
Authors: Simon Green, Sheelagh Frame, Sian Anderson, Morag Hogben, David MacCallum, Gavin Wood, Stuart Wilson, Paul Workman, Edward McDonald, Daniella Zheleva
Journal: Cancer Research (2009)

Seliciclib (CYC202, R-roscovitine) is a tri-substituted purine inhibitor of CDKs 2, 7 and 9 that is currently in Phase II clinical development in patients with advanced NSCLC and Nasopharyngeal Cancer.  In vivo  seliciclib is rapidly metabolised to an inactive carboxylate. A project was initiated to identify derivatives of seliciclib that had a different metabolic profile and improved potency. A series of tri-substituted purines were synthesised and screened in kinase assays to confirm that they had a similar CDK inhibitor profile. The more potent compounds were then analysed in a screening cascade to demonstrate that they had a similar cellular mode-of-action profile to seliciclib. This included evaluation of the compound effects on 1) cell cycle profile; 2) gene expression changes and 3) phosphorylation status of known CDK substrates. All the compounds analysed behaved very similarly to seliciclib but with up to a 40-fold improvement in cellular potency. Four compounds were selected for more in-depth studies including  in vitro  ADME & specificity assays, and  in vivo  pharmacokinetic & xenograft models. Compared to seliciclib significantly improved efficacy has been obtained with once a day oral dosing. Based on the superior pharmaceutical properties and  in vivo  efficacy one molecule was selected for further development. Results from these ongoing studies will be presented.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3863.
Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still’s disease
Authors: Cem Gabay, Bruno Fautrel, Jürgen Rech, François Spertini, Eugen Feist, Ina Kötter, Eric Hachulla, Jacques Morel, Thierry Schaeverbeke, Mohamed A Hamidou, Thierry Martin, Bernhard Hellmich, Peter Lamprecht, Hendrik Schulze-Koops, Delphine Sophie Courvoisier, Andrew Sleight, Eduardo Jorge Schiffrin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease; its management is largely empirical. This is the first clinical study to determine if interleukin (IL)-18 inhibition, using the recombinant human IL-18 binding protein, tadekinig alfa, is a therapeutic option in AOSD. <h3>Methods</h3> In this phase II, open-label study, patients were ≥18 years with active AOSD plus fever or C reactive protein (CRP) levels ≥10 mg/L despite treatment with prednisone and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Previous biological DMARD treatment was permitted. Patients received tadekinig alfa 80 mg or 160 mg subcutaneously three times per week for 12 weeks; those receiving 80 mg not achieving early predicted response criteria (reduction of ≥50% CRP values from baseline and fever resolution) were up-titrated to 160 mg for a further 12 weeks. The primary endpoint was the occurrence of adverse events (AEs) throughout the study. <h3>Results</h3> Ten patients were assigned to receive 80 mg tadekinig alfa and 13 patients to the 160 mg dose. One hundred and fifty-five treatment-emerging AEs were recorded, and 47 were considered related to the study drug. Most AEs were mild and resolved after drug discontinuation. Three serious AEs occurred, one possibly related to treatment (toxic optic neuropathy). At week 3, 5 of 10 patients receiving 80 mg and 6 of 12 patients receiving 160 mg achieved the predefined response criteria. <h3>Conclusions</h3> Our results indicate that tadekinig alfa appears to have a favourable safety profile and is associated with early signs of efficacy in patients with AOSD. <h3>Trial registration number</h3> NCT02398435.
Sténoses anastomotiques oesophagiennes après chirurgie carcinologique: facteurs de risque de sténose réfractaire à la prise en charge endoscopique
Authors: I Kouchner, F Hec, J Branche, E Drumez, T Crombé, B Pariente, A Gandon, G Piessen, R Gérard
Journal: Endoscopy (2018)

La sténose anastomotique bénigne est la principale complication de l'oesophagectomie à visée carcinologique altérant la qualité de vie des patients. La dilatation endoscopique est le traitement de première intention, avec une bonne efficacité immédiate. Néanmoins, la récidive est fréquente justifiant le recours à des procédures endoscopiques itératives. L'objectif principal de notre étude était de déterminer les facteurs prédictifs de sténose anastomotique réfractaire au traitement endoscopique (nécessitant soit plus de 5 endoscopies, soit une intervention chirurgicale). Les objectifs secondaires étaient de déterminer le taux de sténose anastomotique, de déterminer la morbidité des dilatations endoscopiques, d'évaluer le type de technique endoscopique de seconde ligne en cas de d'échec des dilatations, de déterminer l'efficacité et la morbidité des prothèses oesophagiennes dans cette indication, et enfin de déterminer le taux de recours à la chirurgie pour sténose.
Drainage endoscopique des stenoses hilaires: Combien de segments hépatiques doit-on drainé pour augmenter la survie des patients?
Authors: F Caillol, E Bories, C Zemmour, C Pesenti, JP Ratone, J Ewald, O Turrini, JR Delpero, M Giovannini
Journal: Endoscopy (2018)

L' ESGE a statué en 2012 que plus de 50% du foie devait être drainé en cas de sténose hilaire non résécable, bien que les avantages d'un drainage bilateral puissent être discuté par rapport à un drainage unilatéral. Pour tenter de répondre à ces données contradictoires, nous avons évalué nos drainages hilaires pour sténose maligne non résécable en évaluant le pourcentage de foie drainé (calculé sur la base du nombre de segment drainé) et le suivi de nos patients.
Définition et description des lésions vasculaires de l'intestin grêle en vidéo capsule endoscopique: Consensus international selon la méthodologie Delphi
Authors: R Leenhardt, C Li, A Koulaouzidis, F Cavallaro, F Cholet, A Eliakim, I Fernandez-Urien, U Kopylov, ME Mcalindon, A Németh, J Plevris, G Rahmi, E Rondonotti, JC Saurin, G Tontini, E Toth, D Yung, P Marteau, X Dray
Journal: Endoscopy (2018)

Malgré l'existence d'une terminologie validée en vidéo capsule endoscopique (VCE) (1), il n'existe pas de définition consensuelle des lésions vasculaires de l'intestin grêle. Ainsi, leur diagnostic repose essentiellement sur l'expérience du lecteur, avec une part subjective, et un impact potentiellement négatif sur la qualité des soins, des comptes rendus, des actions de formation, et sur la recherche. L'objectif de cette étude était d'établir un consensus international sur la description des lésions vasculaires de l'intestin grêle les plus fréquemment visualisées en VCE.
Profiles of screen-failures in phase 1 clinical trials.
Authors: Emmanuelle Kempf, Lemoine Nathalie, Gabrielle Tergemina-Clain, Sophie Postel-Vinay, Emilie Lanoy, Jean-Charles Soria, Antoine Hollebecque
Journal: Journal of Clinical Oncology (2015)

e17518 Background: To be enrolled into a Phase I clinical trial (P1) patients have to fulfill inclusion criteria. Despite satisfying them at the time of informed consent form signature, a significant proportion of patients can eventually not receive the study drug and is consequently considered as screen-failure (SF). The objective of our study was to describe the frequency and reasons for SF, the profile of patients. Methods: All patients included in P1 at Gustave Roussy from 2008 to 2013 were reviewed retrospectively to identify SF cases. Patients' characteristics, tumor type and stage, experimental drug type and SF reason were analyzed. Reason for SF was classified into four groups: clinical cancer progression, P1 feasibility (promoter or investigator decision, patient’s consent withdrawal), chemistry out of protocol-specified range and relevant comorbidity. Results: Among 1,293 patients, 193 (15%) SF were identified: median age was 57 years (interquartile range (IQR) = [49-64]), 57% were men, 12% had been previously included in P1, median home-center distance was 82 km (IQR = [21-408]), median number of previous systemic lines was 3 (IQR = [2-4]), 45% had > 2 metastatic sites, 39% of LDH values were upper normal limit, 42% of albumin ones were < 35 g/L. Primary tumor site was: 18% of lung cancer, 13% colorectal cancer, 10% breast cancer, 9% melanoma and 8% prostate cancer. Type of experimental drug types included drugs targeting intracellular signaling pathway (77), antiangiogenics (35), cytotoxics (28), immunotherapy (24), hormonotherapy (9). Reasons for SF in all patients were cancer progression in 45%, P1 feasability in 23%, chemistry out of protocol-specified range in 16.5% and relevant comorbidity in 15.5%. Respective figures were 39%, 39%, 16% and 6% for drugs targeting signaling pathway and 54%, 14%, 23%, 9% for antiangiogenics. Conclusions: Cancer progression is responsible of nearly 50% of SF. Physicians should devote particular attention on tumor aggressivity while promoters could try to shorten wash-out period. An upcoming case-controlled study will help to identify SF risk factors.
Racial, Ethnic, and Socioeconomic Differences in Childhood Diet and Teenage Food Allergy
Authors: Elise Coulson, Sheryl Rifas-Shiman, Joanne Sordillo, Supinda Bunyavanich, Carlos A. Camargo, Thomas A.E. Platts-Mills, Brent Coull, Heiki Gibson, Mathew Gillman, Emily Oken, Diane Gold, Mary Rice
Journal: Journal of Allergy and Clinical Immunology (2018)
Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice
Authors: Xilin Wu, Jia Guo, Mengyue Niu, Minghui An, Li Liu, Hui Wang, Xia Jin, Qi Zhang, Ka Shing Lam, Tongjin Wu, Hua Wang, Qian Wang, Yanhua Du, Jingjing Li, Lin Cheng, Hang Ying Tang, Hong Shang, Linqi Zhang, Paul Zhou, Zhiwei Chen
Journal: Journal of Clinical Investigation (2018)

The discovery of an HIV-1 cure remains a medical challenge because the virus rebounds quickly after the cessation of combination antiretroviral therapy (cART). Here, we investigate the potential of an engineered tandem bispecific broadly neutralizing antibody (bs-bnAb) as an innovative product for HIV-1 prophylactic and therapeutic interventions. We discovered that by preserving 2 single-chain variable fragment (scFv) binding domains of each parental bnAb, a single gene-encoded tandem bs-bnAb, BiIA-SG, displayed substantially improved breadth and potency. BiIA-SG neutralized all 124 HIV-1-pseudotyped viruses tested, including global subtypes/recombinant forms, transmitted/founder viruses, variants not susceptible to parental bnAbs and to many other bnAbs with an average IC50 value of 0.073 μg/ml (range < 0.001-1.03 μg/ml). In humanized mice, an injection of BiIA-SG conferred sterile protection when administered prior to challenges with diverse live HIV-1 stains. Moreover, whereas BiIA-SG delayed viral rebound in a short-term therapeutic setting when combined with cART, a single injection of adeno-associated virus-transferred (AAV-transferred) BiIA-SG gene resulted dose-dependently in prolonged in vivo expression of BiIA-SG, which was associated with complete viremia control and subsequent elimination of infected cells in humanized mice. These results warrant the clinical development of BiIA-SG as a promising bs-bnAb-based biomedical intervention for the prevention and treatment of HIV-1 infection.
Interim estimate of influenza vaccine effectiveness in hospitalised children, Hong Kong, 2017/18
Authors: Susan S Chiu, Mike Y W Kwan, Shuo Feng, Joshua S C Wong, Chi-Wai Leung, Eunice L Y Chan, J S Malik Peiris, Benjamin J Cowling
Journal: Eurosurveillance (2018)

We conducted a hospital-based test-negative study in Hong Kong to estimate influenza vaccine effectiveness (VE) for the winter of 2017/18. The interim analysis included data on 1,078 children admitted between 4 December 2017 and 31 January 2018 with febrile acute respiratory illness and tested for influenza. We estimated influenza VE at 66% (95% confidence interval (CI): 43–79) overall, and 65% (95% CI: 40–80) against influenza B, the dominant virus type (predominantly B/Yamagata).
Long-term result of endoscopic treatment of an ampullary adenoma with extension into the common bile duct
Authors: Rodrigo Scomparin, Luiza Bento, Clelma Batista, Marcelo de Lima, Gustavo de Paulo, Bruno Martins, Fauze Maluf-Filho
Journal: Endoscopy (2018)

A 56-year-old man with chronic hepatic disease due to hepatitis C and esophageal varices was referred to our hospital with an elevated alpha-fetoprotein level and a solid lesion in the distal common bile duct (CBD) seen on computed tomography (CT) scanning. This lesion was protruding into the second part of the duodenum and causing dilatation of the biliary tree. An upper gastrointestinal endoscopy revealed a raised lesion at the major duodenal papilla ([Fig. 1]). Biopsies showed a tubular adenoma with low grade dysplasia. Endoscopic ultrasound (EUS) revealed thickening that was restricted to the mucosal layer and choledocholithiasis.
Abstract 12906: Generation of Induced Pluripotent Stem Cells and Cardiomyocytes as a Cellular Model of Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Dongrui Ma, Heming Wei, Guangqin Zhang, Jun Lu, Shuswen Ho, Xiaoming Sun, Yingzi Oh, Winston Shim, Philip Wong, Reginald Liew
Journal: Circulation (2011)

Introduction:  Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder primarily affecting heart muscle and is associated with a high risk of ventricular arrhythmias and sudden cardiac death. Diagnosis is currently based upon clinical criteria and can be easily missed in the early stages. The pathophysiological studies of ARVC are being hampered by a lack of human models.   Hypotheses:  Functional cardiomyocytes can be derived from ARVC patient-specific induced pluripotent stem cells (iPSC) and used as a cellular disease model.   Methods:  Several iPSC lines were reprogrammed from dermal fibroblasts of an ARVC patient via retroviral transduction of 4 Yamanaka factors. These iPSC lines were characterized by immuno-staining, Real-time PCR, DNA methylation, and telomerase activity studies. Moreover, contracting embryoid bodies (EBs) were generated from iPSC and cardiomyocytes were characterized by immuno-staining, Real-time PCR, patch-clamp and confocal Ca2+ imaging.   Results:  Four ARVC iPSC lines were generated from a patient with ARVC (PKP2 mutation); iPSCs shared similar characteristics with H9 human embryonic stem cells (hESCs), including high expression of pluripotency markers (Oct-4, SSEA-4, TRA1-60 and TRA1-81), high telomerase activity, and overall demethylation status of the promoter of Oct-4 and Nanog. In addition, contracting cardiomyocytes differentiated from ARVC-iPSCs expressed typical cardiac markers (alpha-Actinin and beta-MHC) and a ventricular action potential profile was observed in the majority of cardiomyocytes (>70%). Normal patterns of action potentials were observed. Interestingly, compared to H9 hESC-derived cardiomyocytes, higher Ca2+ transient amplitudes were noted with ARVC patient derived cardiomyocytes.   Conclusion:  we have successfully generated iPSC lines from an ARVC patient and differentiated them into cardiomyocytes. Our preliminary results suggest that abnormal Ca2+ handling can be observed at an early stage in iPSC-derived cardiomyocytes from patients with ARVC.