David Cohen

Bio: David Cohen is an academic researcher from Pierre-and-Marie-Curie University. The author has contributed to research in topics: Medicine & Autism. The author has an hindex of 83, co-authored 635 publications receiving 37722 citations. Previous affiliations of David Cohen include University of California, Berkeley & University of Michigan.

A randomized phase II study of bevacizumab and weekly anetumab ravtansine or weekly paclitaxel in platinum-resistant or refractory ovarian cancer NCI trial#10150.

Abstract: 5514 Background: Mesothelin and its binder, antigen-CA125, are highly expressed in high grade serous and endometrioid ovarian cancers (HGOC) and, can inhibit paclitaxel-induced cell death. Anetumab ravtansine (AR) is a fully-human antibody directed at the mesothelin antigen, conjugated to a tubulin polymerization inhibitor. We assessed the safety and activity of the combination AR/bevacizumab (ARB) versus weekly paclitaxel/bevacizumab (PB) in patients (pts) with platinum resistant HGOC. Methods: An initial run-in phase I assessed the safety of ARB. After determination of the recommended phase 2 dose (RP2D), a multicenter 1:1 randomized phase 2 trial was designed to evaluate the progression free survival (PFS) in pts with platinum resistant/refractory HGOC. Pts were stratified by platinum resistant or refractory and prior bevacizumab (bev). Eligibility required measurable disease and mesothelin tested positive centrally on archival tissue by IHC. No limitation on the number of prior lines of therapy. A futility analysis was planned at 35 PFS events. The control arm was weekly intravenous paclitaxel 80mg/m2 with bev 10mg/kg every 2 weeks. A CT was performed every 8 weeks for RECIST1.1 assessment. The toxicities were reported according to CTCAE version 5.1. NCT03587311. Results: 7 pts were enrolled in the run-in phase 1 and the RP2D determined as bev (10mg/kg) biweekly with AR (2.2mg/kg) weekly on a 28 day-cycle. In the phase 2, 57 pts were enrolled, 28 pts in the ARB and 29 pts in the control group. The positivity rate for mesothelin screening was 88%. Pts were heavily pre-treated, median prior lines of 3 (range (1-9) with 24 pts received prior bev (42%) and 13 pts were platinum refractory (7 in ARB and 6 in PB). At the time of 35 PFS events, one CR and 4 PR were observed (ORR = 18%) in the ARB arm, versus no CR and 16 PR in the weekly PB (ORR = 55%). The estimated median PFS was 5.3 (95% CI: 3.7-7.4) months for ARB and 9.6 (95% CI: 7.4-17.4) months for PB (HR = 1.7(95% CI: 0.9-3.4)). The median number of cycles were 4 (1, 29) and 8 (1, 19) respectively. The most common treatment-related AEs in the ARB arm were mostly grade 1/2 increase AST (71%) and ALT (64%), thrombocytopenia (61%), fatigue (57%), and peripheral neuropathy (46%). In the PB arm, the most common treatment-related AE were anemia (66%), neutropenia (59%), epistaxis (48%), fatigue (45%) and peripheral neuropathy (45%). Conclusions: At the time of futility analysis, weekly PB had better outcome than weekly ARB leading to the study termination. Molecular and blood analyses are on-going to assess potential biomarkers of response. This study highlights the importance of randomization in assessment of novel therapies and potential for re-challenge with bevacizumab. These data show that weekly PB is an effective regimen and can be considered as the control arm in platinum resistant HGOC. Clinical trial information: NCT03587311.

Life Events: Worries and Suicide Attempts Implications in Adolescents

Abstract: Background: Suicide is the second leading causes of death among 15- to 19-years oldThe onset of adverse life events represent important proximal risk factors for suicidal beahviorsThe objectives of this study are to determine the patterns Methods and Findings: This study used a case-control design in which a sample of 136 adolescents who had attempted suicide was contrasted with 658 community controls The measures included sociodemographic factors; the Adolescent Life Change Event Scale (ALCES), which is a self-administered questionnaire that explores the onset of stressful life events; and the State Worry Questionnaire (SWQ), which measures the level of worries across five distinct domains According to the results of multiple logistic regressions, adolescents who had attempted suicide reported elevated rates of both stressful life events and worries Multiple logistic regression analysis showed that adolescents who had attempted suicide were more likely to have experienced three categories of life events were more specifically associated with suicidal attempt: (1) stressful life events related to one’s family characteristics (parental divorce/separation); (2) the disruption of an affective relationship (eg, a romantic break-up or the death of a close friend); or (3) legal or disciplinary problems (eg, school disciplinary problems or expulsion) These life events were associated with a definite increase in the total SWQ score, specifically on the SWQ “aimless future” subscale Conclusions: This data indirectly confirms that a surge in adolescents’s level of worry is one of the mechanism by which a stressful life event could precipitate suicidal behaviors However, particular attention should be paid to the assessment of suicidality in context of disruptive disorders in adolescents, as the social consequences of these symptoms represent an important risk for suicidal behaviors, and moreover, irrespective of the level of worry

Willingness To Pay To Eliminate the Risk of Restenosis Following Percutaneous Coronary Intervention A Contingent Valuation

Abstract: Background—Percutaneous coronary intervention (PCI) remains limited by the risk of restenosis. Patients' perceptions of the health benefits and value of avoiding restenosis are incompletely known. Methods and Results—We used a contingent valuation approach to assess the willingness to pay (WTP) for a hypothetical treatment that eliminates the risk of restenosis among 270 PCI patients. Patients were provided with a scenario describing a baseline 10% or 20% probability of restenosis in the year following the procedure, which could lead to repeat PCI or, more rarely, bypass surgery, without any increase in mortality. Six different “take it or leave it” bids ($500, $1000, $1500, $2000, $2500, and $3000) and both risk levels were randomly assigned. Multiple logistic regression was used to identify independent predictors of a positive response to the WTP question. Using nonparametric methods, the median WTP to eliminate the risk of restenosis was estimated at $2802. As expected, higher income was independently ...

Health Care Trajectories for Children With ADHD in France: Results From the QUEST Survey

Abstract: Objective: The objective of this study is to retrospectively describe the pathway toward ADHD diagnosis and treatment, and identify potential areas for improvement. Method: Parent-reported questionnaires were collected by a national sample of ADHD specialists. Results: In total, 473 complete questionnaires were analyzed. Initial onset of ADHD symptoms was reported at a mean age of 4.45 years. Mean age at diagnosis was 8.07 years, and half of the families had seen at least three health care professionals previously. Psychiatrists were most commonly consulted. A "combined" (89% boys) and inattentive (49% boys) profile was identified. Diagnosis was made 1 year later for the latter group. Two thirds of patients received pharmacological treatment. The delay in diagnosis was identified as the main source of concern for caregivers. Conclusion: The 4-year delay in diagnosis may represent a loss of opportunity. Training health care professionals in the core symptoms of ADHD may help reduce disparities and improve patient trajectory.

Social Signal Processing and Socially Assistive Robotics in Developmental Disorders.

Abstract: Recently, there have been considerable advances in the research on innovative information communication technology (ICT) for the education of people with autism. This review focuses on two aims: (1) to provide an overview of the recent ICT applications used in the treatment of autism and (2) to focus on the early development of imitation and joint attention in the context of children with autism as well as robotics. There have been a variety of recent ICT applications in autism, which include the use of interactive environments implemented in computers and special input devices, virtual environments, avatars and serious games as well as telerehabilitation. Despite exciting preliminary results, the use of ICT remains limited. Many of the existing ICTs have limited capabilities and performance in actual interactive conditions. Clinically, most ICT proposals have not been validated beyond proof of concept studies. Robotics systems, developed as interactive devices for children with autism, have been used to assess the child’s response to robot behaviors; to elicit behaviors that are promoted in the child; to model, teach and practice a skill; and to provide feed-back on performance in specific environments (e.g., therapeutic sessions). Based on their importance for both early development and for building autonomous robots that have human-like abilities, imitation, joint attention and interactive engagement are key issues in the development of assistive robotics for autism and should be the focus of further research.

Using Multivariate Statistics

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How people learn: Brain, mind, experience, and school.

Abstract: New developments in the science of learning science of learning overview mind and brain how experts differ from novices how children learn learning and transfer the learning environment curriculum, instruction and commnity effective teaching - examples in history, mathematics and science teacher learning technology to support learning conclusions from new developments in the science of learning.

ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting With ST-Segment Elevation

Abstract: ACE : angiotensin-converting enzyme ACS : acute coronary syndrome ADP : adenosine diphosphate AF : atrial fibrillation AMI : acute myocardial infarction AV : atrioventricular AIDA-4 : Abciximab Intracoronary vs. intravenously Drug Application APACHE II : Acute Physiology Aand Chronic

Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association

Abstract: WRITING GROUP MEMBERS Emelia J. Benjamin, MD, SCM, FAHA Michael J. Blaha, MD, MPH Stephanie E. Chiuve, ScD Mary Cushman, MD, MSc, FAHA Sandeep R. Das, MD, MPH, FAHA Rajat Deo, MD, MTR Sarah D. de Ferranti, MD, MPH James Floyd, MD, MS Myriam Fornage, PhD, FAHA Cathleen Gillespie, MS Carmen R. Isasi, MD, PhD, FAHA Monik C. Jiménez, ScD, SM Lori Chaffin Jordan, MD, PhD Suzanne E. Judd, PhD Daniel Lackland, DrPH, FAHA Judith H. Lichtman, PhD, MPH, FAHA Lynda Lisabeth, PhD, MPH, FAHA Simin Liu, MD, ScD, FAHA Chris T. Longenecker, MD Rachel H. Mackey, PhD, MPH, FAHA Kunihiro Matsushita, MD, PhD, FAHA Dariush Mozaffarian, MD, DrPH, FAHA Michael E. Mussolino, PhD, FAHA Khurram Nasir, MD, MPH, FAHA Robert W. Neumar, MD, PhD, FAHA Latha Palaniappan, MD, MS, FAHA Dilip K. Pandey, MBBS, MS, PhD, FAHA Ravi R. Thiagarajan, MD, MPH Mathew J. Reeves, PhD Matthew Ritchey, PT, DPT, OCS, MPH Carlos J. Rodriguez, MD, MPH, FAHA Gregory A. Roth, MD, MPH Wayne D. Rosamond, PhD, FAHA Comilla Sasson, MD, PhD, FAHA Amytis Towfighi, MD Connie W. Tsao, MD, MPH Melanie B. Turner, MPH Salim S. Virani, MD, PhD, FAHA Jenifer H. Voeks, PhD Joshua Z. Willey, MD, MS John T. Wilkins, MD Jason HY. Wu, MSc, PhD, FAHA Heather M. Alger, PhD Sally S. Wong, PhD, RD, CDN, FAHA Paul Muntner, PhD, MHSc On behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics—2017 Update

Heart Disease and Stroke Statistics—2016 Update: A Report From the American Heart Association

Abstract: Author(s): Writing Group Members; Mozaffarian, Dariush; Benjamin, Emelia J; Go, Alan S; Arnett, Donna K; Blaha, Michael J; Cushman, Mary; Das, Sandeep R; de Ferranti, Sarah; Despres, Jean-Pierre; Fullerton, Heather J; Howard, Virginia J; Huffman, Mark D; Isasi, Carmen R; Jimenez, Monik C; Judd, Suzanne E; Kissela, Brett M; Lichtman, Judith H; Lisabeth, Lynda D; Liu, Simin; Mackey, Rachel H; Magid, David J; McGuire, Darren K; Mohler, Emile R; Moy, Claudia S; Muntner, Paul; Mussolino, Michael E; Nasir, Khurram; Neumar, Robert W; Nichol, Graham; Palaniappan, Latha; Pandey, Dilip K; Reeves, Mathew J; Rodriguez, Carlos J; Rosamond, Wayne; Sorlie, Paul D; Stein, Joel; Towfighi, Amytis; Turan, Tanya N; Virani, Salim S; Woo, Daniel; Yeh, Robert W; Turner, Melanie B; American Heart Association Statistics Committee; Stroke Statistics Subcommittee