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Krajňák, Samuel, Katarína Staronova, and Heath Pickering. "Ministerial Advisers in Slovakia: Profiles and Career Paths, 2010 – 2020." NISPAcee Journal of Public Administration and Policy 13, no. 2 (2020): 115–40. http://dx.doi.org/10.2478/nispa-2020-0017.
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AbstractThis study examines the transparency of the regulatory framework under which ministerial advisors exist within the politicized context of a Central and Eastern European perspective. We compare profiles and career paths of ministerial advisers under five different types of coalition governments and examine if variance across government types can be explained by type of party – established vs. new parties. Empirically, the article draws on a cohort of 162 ministerial advisers in Slovakia across five governments from 2010 to 2020. We arrive at multiple findings. Firstly, we suggest the limitation in the availability and reporting of data is an important finding as it highlights accountability gaps and lack of government transparency irrespective of the party in power. Secondly, within the low regulatory environment, ministers appoint multiple types of staff including both formal “visible” ministerial advisers and “invisible” ministerial agents that, if one could accurately measure, would likely demonstrate that the ministerial advisory system is more inflated than we currently present. The ad-hoc nature of the advisory system also creates fluctuations in the size of the ministerial adviser cohort across governments and across different ministries. This would also help to explain the next finding, which is that, contrary to the experience in many countries, the overall size of the advisor population does not grow, probably because executive politicians have other avenues of appointing advisory agents. Fourthly, the advisers have a fairly equal distribution of prior employment from both the public sector and the private sector, but we do see some evidence of more established political parties preferring to recruit from the public sector and newer parties preferring to recruit from the private sector. Lastly, the appointment process appears to be highly controlled by individual ministers, suggesting personal ties are essential (link between ministerial and advisor education) and party-political criteria are a low consideration. The research is conducted using a biographical approach in which freedom of information requests and open source data is scrapped and then triangulated via a dozen interviews with current and former advisers. It argues that regulation is weak, lacking public scrutiny, which provides loopholes for employing ministerial agents in informal ways that could create, at worst, the opportunity for corrupt behavior, or at least, lead to poor practices in good governance. Therefore, future research should focus on both the formal “visible” and informal “invisible” ways that ministers recruit their advisory agents, how their agents function, and whether existing regulatory measures create a transparent and accountable governance framework.
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H. Walsh, John. "SEC’s examination program issues a risk alert on investment adviser due diligence processes." Journal of Investment Compliance 15, no. 2 (2014): 26–28. http://dx.doi.org/10.1108/joic-05-2014-0019.
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Purpose – To summarize and interpret a Risk Alert titled “Investment Adviser Due Diligence Processes for Selecting Alternative Investments and their Respective Managers,” issued by the USA Securities and Exchange Commission Office of Compliance Inspections and Examinations on January 28, 2014. Design/methodology/approach – Focuses on investment advisers selecting underlying alternative investment managers. Discusses the scope of the Staff’s observations. Describes several due diligence practices observed by the staff, including seeking greater transparency; utilizing third-party information aggregators, administrators, custodians, and auditors; using more quantitative analysis; and extending due diligence process to include operational and liquidity reviews. Lists several observed warning indicators that could lead an advisor to conduct additional due diligence, request the underlying manager to make appropriate changes, or reject or veto an investment. Identifies both positive and negative compliance practices. Findings – The Risk Alert noted several observed risk indicators that could lead an adviser to conduct additional due diligence, request the underlying manager to make appropriate changes, or reject or veto the investment. Advisers can assume that SEC Staff will ask about these risks in future adviser examinations. Originality/value – Practical guidance from an experienced financial services and securities lawyer.
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Barnes, Benita J. "The Nature of Exemplary Doctoral Advisors' Expectations and the Ways They May Influence Doctoral Persistence." Journal of College Student Retention: Research, Theory & Practice 11, no. 3 (2009): 323–43. http://dx.doi.org/10.2190/cs.11.3.b.
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The high attrition rate from doctoral programs has been called a “hidden crisis” in graduate education (Lovitts & Nelson, 2000). Previous research has identified a constellation of factors that may contribute to doctoral attrition. However, the literature suggests that one of the most powerful influences on doctoral persistence is the relationship doctoral students develop with their advisors (Berg & Ferber, 1983; Ferrer de Valero, 2001; Girves & Wemmerus, 1988). Although there is a growing body of literature that has explored the advisor-advisee relationship with respect to persistence, little attention has been given to the examination of the expectations that advisors have of their advisees and how these expectations might impact degree completion. Therefore, this exploratory qualitative study examined the expectations that 25 exemplary advisors have of their doctoral advisees. Findings revealed 5 specific expectations advisors hold that, if met, could lead to improved doctoral student retention.
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Craft, Christy Moran, Donna Augustine-Shaw, Amanda Fairbanks, and Gayla Adams-Wright. "Advising Doctoral Students in Education Programs." NACADA Journal 36, no. 1 (2016): 54–65. http://dx.doi.org/10.12930/nacada-15-013.
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Because almost one half of students enrolled in American doctoral programs do not complete their degrees, the factors that lead to doctoral student attrition need to be identified. Research suggests that the nature of the advisor–advisee relationship contributes to the persistence levels of doctoral students. In this study, we conducted a content analysis of institutional documents related to advising in two types of doctoral programs in education. Using data collected from a purposeful sample from universities, we analyzed policies, procedures, and expectations related to doctoral student advising. The findings lead to important implications for clarifying roles of advisors and expectations for graduate student advising.
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Stillman, Andrew. "Institutional Evaluation and LEA Advisory Services: Research Findings from the NFER LEA Advisers Project." Research Papers in Education 4, no. 2 (1989): 3–27. http://dx.doi.org/10.1080/0267152890040202.
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Kaur, Mandeep, and Tina Vohra. "Factors influencing the choice of financial advisor by women stock investors in Punjab." International Journal of Law and Management 59, no. 2 (2017): 192–201. http://dx.doi.org/10.1108/ijlma-09-2015-0051.
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Purpose The paper aims to attempt to identify the attributes that women look for in their financial advisor and to examine if the choice of attributes of a financial advisor among women investors in Punjab is the same across demographics. The understanding of the attributes that women want in their financial advisor will help the financial advisors to be mindful of the opportunities and the challenges they have to face while working with women investors. Studying the impact of demographics on the choice of the investment advisor would enable the service providers to provide women with services relevant to their unique and individual situations. Design/methodology/approach A pre-tested, well-structured questionnaire was constructed and administered personally, and the responses of 200 women investors were analyzed. The sum of the ranks assigned by women to various attributes determining the choice of a financial advisor was used to find out the most preferred attribute on the basis of which women choose their financial advisor. The Kruskal Wallis test was used to analyze the impact of demographics on the choice of the respondents. Findings The results of the study brought out that the friendliness of the financial advisor, and the quality of advice provided by them are preferred attributes determining the choice of a financial advisor. Along with this, the results also state that the preference for the attribute friendliness and quality of advice is not the same across age groups. The choice of attributes also varies according to the marital status of the respondents. Practical implications The current study will contribute toward a greater understanding of the attributes which are considered important by women while choosing their financial advisor. The study will help the financial advisors to cater to the needs of their women clients. Moreover, the study will also benefit women by bringing about a positive change in the attitude of the financial advisors in favor of them. The greater sensitization of the financial advisors toward their women clients would lead to greater stock market participation among women, thereby benefitting the society. Originality/value The paper is an attempt to identify the attributes that women look for in their financial advisor and to examine if the choice of attributes of a financial advisor among women investors in Punjab is the same across demographics or not. Therefore, the study contributes to the understanding of the investment behavior of women.
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Punyanunt-Carter, Narissra, and Stacy Carter. "Undergraduate Students’ Perceptions of their Advisors: SocioCommunicative Style and Perceptions of Relational Satisfaction." Higher Learning Research Communications 5, no. 2 (2015): 14. http://dx.doi.org/10.18870/hlrc.v5i2.188.
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<p>The goal of the current study was to examine the sociocommunicative styles that college students’ perceive their advisor to be using in their interactions. In addition, the study analyzed what characteristics lead to higher relational satisfaction in the advisor-advisee relationship. Three hundred and ninety-seven college students voluntarily completed a survey on their current advisor. Results revealed that there is a significant relationship between sociocommunicative style and relationship satisfaction.</p>
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Tudor, Thomas R. "Fully integrating academic advising with career coaching to increase student retention, graduation rates and future job satisfaction." Industry and Higher Education 32, no. 2 (2018): 73–79. http://dx.doi.org/10.1177/0950422218759928.
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Higher education institutions in the United States are under increasing pressure to retain and graduate more students. Traditionally, the academic advisor helps students to meet degree graduation requirements and may also do some minor career advising. A new approach is proposed, in which career coaching with industry help becomes just as important and is formalized into the academic advisor’s role. Under this approach, students are advised in relation not only to their progress towards their degree, but also to their progress towards their career. They undergo a required process to choose a career and must make progress towards it while pursuing their degree. The use of formal career coaching combined with academic advising is based on goal-setting theory and career planning research. This new approach to advising may lead to increased student retention and graduation rates and also to higher job satisfaction after graduation.
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Kyte, Sarah Blanchard, Elizabeth Collins, and Regina Deil-Amen. "Mindset Messaging: Fostering Student Support and Confidence through Micro-Messaging in Advisor Communication." NACADA Journal 40, no. 1 (2020): 36–48. http://dx.doi.org/10.12930/nacada-19-08.
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As academic advisors help students navigate academic challenges toward a degree, seemingly mundane interactions have the potential to shape students' beliefs about themselves and their abilities. This study examines whether subtle cues within messages from advisors may help students develop what Carol Dweck calls a growth mindset—the belief that ability is malleable through effort, strategy, and help-seeking—and lead to greater perceived support from advisors and student confidence. Drawing on focus groups and interviews with twenty undergraduate students at a large public university, this study offers empirical support for the positive impact that growth mindset language can have within advisor-student communication, as well as a set of practical recommendations for bringing these insights to day-to-day advising practice.
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Bachmann, Kremena. "Can advisors eliminate the outcome bias in judgements and outcome-based emotions?" Review of Behavioral Finance 10, no. 4 (2018): 336–52. http://dx.doi.org/10.1108/rbf-11-2016-0072.
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Purpose An outcome bias occurs when performance is evaluated based upon the outcome of the decision rather than upon the quality of the decision itself. The purpose of this paper is to test experimentally whether advisors eliminating the uncertainty in the quality of decisions as a potential driver of the outcome bias can eliminate this bias in judgements. Additionally, the paper analyses whether such advisors can attenuate the emotional experience after decisions’ outcomes by supporting the cognitive understanding of these outcomes. Design/methodology/approach The paper employs a between-subject experimental setting where decision makers are asked to make investment decisions. The two variables manipulated were advice (receiving advice vs deciding without an advice) and state (loss vs neutral vs gain state). Participants were randomly assigned to each group. One group completed all tasks while receiving advice before making a final decision. Another group completed all tasks without any advice. After completing each investment task, participants were randomly assigned to one of three possible states that determine their payoff. Findings The results reveal that advisors eliminating the uncertainty in the quality of decision can eliminate the outcome bias in the judgements of decision quality, especially after bad outcomes. Nevertheless, after controlling for the perceived quality of the decisions, advised individuals show a greater emotional sensitivity to bad outcomes than non-advised decision makers. These observations suggest that advisors eliminating the uncertainty in the decision quality can improve the understanding that good decisions can lead to bad outcomes just by chance, but they are not able to prevent affective reactions after bad outcomes; on the contrary, they may even reinforce them. Research limitations/implications The observation that, after bad outcomes, advised decision makers are less willing to decide the same way than non-advised decision makers is consistent with empirical findings on the risk-taking behaviour of self-directed and mutual fund investors. Self-directed investors are less likely to revise their decision and sell an investment at a loss than mutual fund investors (Chang et al., 2016). While investors might sell funds because they are unable to observe the decision process of the manager and use the outcome to judge the manager’s skills, this study shows that such learning from decision outcomes is not necessary for observing the risk-taking behaviour of the investors. Even if the decision process of the advisor is observable (as in this study), the decision makers’ willingness to decide the same way is influenced by the losses – an effect that goes beyond the assessed quality of advice as the results of this study show. Practical implications The results of this study have important implications for advisors aiming to maintain a positive relationship with their clients. Convincing clients that an advice is optimal supports their understanding that a good advice can have bad outcomes. However, this understanding may not prevent affective reactions after bad outcomes. On the contrary, the affective response after bad outcomes is even stronger with the advice than without it. Hence, advisors should address not only issues related to the quality of the provided advice, but also emotional aspects, which could be related to what clients expect from following the advice. Originality/value This study is one of the few that account for the possibility that the outcome bias may arise because there is uncertainty regarding the optimal choice. In particular, this paper uses a much more powerful criterion to define an optimal choice than the expected value criterion used in previous studies. The criterion represents a minimal requirement for rational behaviour in expected utility theory and many non-expected utility theories.
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Wyatt, Neal. "Listening to Advisors: A Conversation About Readers’ Advisory Services, Practice, and Practicing." Reference & User Services Quarterly 59, no. 1 (2019): 2. http://dx.doi.org/10.5860/rusq.59.1.7218.
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As RA service has moved from its second-wave renaissance during the late twentieth century/early twenty-first century (with a steady stream of reference tools, conference programming, and think pieces) into an often underpromoted but bedrock mainstay of the public library, what do advisors continue to discuss among themselves and see as areas of need? If you could gather a handful of advisors together, over a cup of coffee one rainy morning before book group began, what would they talk about? What would they ask each other? What do they know to be foundational about the service? As important, what might they suggest we all re-think? This column invites you to eavesdrop on such a conversation. It was conducted over email between six advisors: two at the start of their careers, two helping to define the field, and two who have lead the way for librarians, for a combined eight decades. These advisors share research, hard-won and lived-in lessons, showcase the luminous nature of RA work as well as its difficulties, propose a change for RA education, and, of course, each suggests a book to read.
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Shockley-Zalabak, Pamela. "Advisors as Interaction Designers." NACADA Journal 32, no. 1 (2012): 12–17. http://dx.doi.org/10.12930/0271-9517-32.1.12.
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Pamela Shockley-Zalabak, Chancellor, University of Colorado Colorado Springs, gave the following speech at the 2011NACADA Annual Conference October 3, 2011, at the Colorado Convention Center in Denver. She provides an overview of changes affecting U.S. higher education, commentary on how those changes affect the role of the academic advisor, and the importance of helping students achieve life goals. She encourages academic advisors to embrace a broad definition of the academic advising profession and to lead change and innovation on campus. She relates personal teaching experiences, including her first instructor job at a federal prison, a chance meeting of a young woman who exemplifies today's college student, and the imperative that academic advisors engage in “disruptive innovation and interaction design” to better serve students.
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Fernandez-Aviles, Gema, and Lorenzo Davila. "A Business Figure In Crisis Time: Independent Financial Adviser." International Business & Economics Research Journal (IBER) 11, no. 13 (2012): 1499. http://dx.doi.org/10.19030/iber.v11i13.7453.
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The figure of the Independent Financial Adviser (IAF) is becoming increasingly relevant in the field of business and finance. However, this figure is relatively new, poorly understood by most investors and uncommon in financial institutions. The purpose of this paper is to determine the factors behind the willingness to pay for the services of an independent financial adviser, as well as the reasons that would lead investors to move from the traditional advisors to the independent ones. We have surveyed over 10,000 potential investors in Spain. Thus, the results are consistent from a statistical point of view.
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Stillman, Andrew. "LEA advisers: change and management." Educational Research 30, no. 3 (1988): 190–201. http://dx.doi.org/10.1080/0013188880300303.
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Agnelli, Giancarlo, Harry Roger Buller, Alexander Cohen, et al. "Two Doses of Apixaban for the Extended Treatment of Venous Thromboembolism." Blood 120, no. 21 (2012): LBA—1—LBA—1. http://dx.doi.org/10.1182/blood.v120.21.lba-1.lba-1.
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Abstract Abstract LBA-1 Background: Apixaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for extended treatment of venous thromboembolism. Objectives: To compare the efficacy and safety of two doses of apixaban (2.5 or 5 mg twice daily) with placebo for the extended treatment of venous thromboembolism in patients who have completed 6 to 12 months of prior anticoagulant therapy. Methods: This randomized, double-blind study (ClinicalTrials.gov number, NCT00633893) compared two apixaban doses (2.5 or 5 mg twice daily) with placebo for 12 months in patients with venous thromboembolism who had completed 6–12 months of anticoagulation. The primary efficacy outcome was symptomatic recurrent venous thromboembolism or all-cause mortality. Secondary efficacy outcomes included (a) the composite of symptomatic venous thromboembolism or venous thromboembolism-related death, and (b) the composite of symptomatic venous thromboembolism, venous thromboembolism-related death, myocardial infarction, stroke, or cardiovascular-related death. The primary safety outcome was major bleeding; the secondary safety outcome was major and clinically relevant non-major bleeding. Results: The study included 2486 patients: 829, 840, and 815 randomized to placebo, apixaban 2.5 mg, and apixaban 5 mg, respectively. Rates of the primary efficacy outcome were 11.6% in the placebo group, compared with 3.8% and 4.2% in the apixaban 2.5 mg and 5 mg groups, respectively (absolute risk differences of 7.8% and 7.4%, respectively; 95% confidence intervals 5.3% to 10.3% and 4.8% to 10%, respectively; p<0.001 for both comparisons). Other outcomes are detailed in the Table. Conclusions: Both doses of apixaban reduced the risk of symptomatic recurrent fatal or non-fatal venous thromboembolism by approximately 80% without increasing the rate of major bleeding. In addition, both apixaban doses reduced arterial thrombotic events. The lower apixaban dose may be preferred for extended treatment, because of the trend for less clinically relevant non-major bleeding. Disclosures: Agnelli: Bristol Myers Squibb: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy; Boehringer Ingelheim: Consultancy; Bayer Healthcare: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Sanofi-Aventis: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Buller:Bayer: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Daiichi: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Sanofi-aventis: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Isis: Consultancy, Research Funding; Thrombogenics: Consultancy, Research Funding. Cohen:Astellas: Consultancy, Research Funding; AstraZenica: Consultancy, Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Boheringer-Ingelheim: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; GlaxoSmithKline: Consultancy, Research Funding; Johnson & Johnson: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Mitsubishi Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Portola: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Schering Plough: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Curto:Pfizer: Employment. Gallus:Pfizer: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Daiichi Sankyo: Consultancy; Bayer: Membership on an entity’s Board of Directors or advisory committees; boehringer-Ingelheim: Membership on an entity’s Board of Directors or advisory committees. Johnson:Pfizer: Employment. Porcari:Pfizer: Employment. Raskob:Pfizer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Bristol Myer Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Johnson & Johnson: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy; Quintiles: Consultancy; National Blood Clot Alliance: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Weitz:Pfizer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria.
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Couturaud, Francis, Olivier Sanchez, Gilles Pernod, et al. "Two Years Versus Six Months of Oral Anticoagulation after a First Episode of Unprovoked Pulmonary Embolism: The Padis PE Multicenter, Double-Blind, Randomized Trial." Blood 124, no. 21 (2014): LBA—3—LBA—3. http://dx.doi.org/10.1182/blood.v124.21.lba-3.lba-3.
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Abstract Background: Patients with a first episode of unprovoked pulmonary embolism have a high risk of recurrent venous thromboembolism (VTE) after anticoagulation is discontinued. Prolongation of anticoagulant therapy beyond the initial period of 3 to 6 months is associated with a significant reduction of recurrent VTE, but an excess of bleeding events. In addition, most studies assessing prolonged treatment did not follow the patients after treatment had been stopped. Thus, the optimal duration of anticoagulation in patients with a first unprovoked pulmonary embolism remains uncertain. Method: In a multicenter, randomized, double-blind, controlled trial, we compared an additional 18 months of warfarin (target International Normalized Ratio, 2 to 3) with placebo in patients with a first episode of unprovoked pulmonary embolism that had been initially treated with a vitamin K antagonist for 6 uninterrupted months. In both groups, all patients were followed up for an additional median period of 2 years after treatment had been stopped. Primary outcome was the composite of recurrent VTE or major bleeding during the 18-month treatment period. Secondary outcomes included the composite outcome during the entire study period (i.e. 18 months plus a median follow-up of 2 years), deaths not caused by pulmonary embolism or major bleeding and the components of the composite outcome during the treatment period and during the entire study period. All outcomes were centrally adjudicated. Results: A total of 371 patients were included in the study and analyzed on an intention-to-treat basis. During the treatment period, the composite outcome occurred in 6 of 184 patients (3.3%) in the warfarin group and in 25 of 187 patients (13.5%) in the placebo group (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.09-0.55; p=0.0004). Recurrent VTE occurred in 3 (1.7%) patients in the warfarin group and in 25 (13.5%) in the placebo group (HR, 0.11; 95%CI, 0.03-0.37); major bleeding occurred in 4 (2.2%) patients in the warfarin group and in 1 (0.5%) in the placebo group (HR, 4.07; 95%CI, 0.45-36.38). Two deaths not related to the study outcome occurred in each group. During the entire median study period of 41 months, the composite outcome occurred in 33 (20.8%) patients in the warfarin group and in 41 (23.5%) in the placebo group (HR, 0.76; 95%CI, 0.48-1.20; p=0.24) (Figure 1). Recurrent VTE occurred in 28 (17.9%) patients in the warfarin group and in 39 (22.1%) in the placebo group (HR, 0.67; 95%CI, 0.41-1.08); major bleeding occurred in 6 (3.5%) patients in the warfarin group and in 4 (2.5%) in the placebo group (HR, 1.57; 95%CI, 0.44-5.55). Thirteen (11.9%) patients died in the warfarin group, four deaths being related to recurrent VTE and one to major bleeding; six (3.6%) patients died in the placebo group from a cause unrelated to recurrent VTE or bleeding (p=0.08). Of the 67 episodes of recurrent VTE, 52 (77.6%) were pulmonary embolism and 58 (86.6%) were unprovoked. Conclusion: After 6 months of anticoagulation for a first episode of unprovoked pulmonary embolism, extending anticoagulation for an additional 18 months was associated with a major reduction in the risk of recurrent VTE or major bleeding during the treatment period. However, this benefit was not maintained after discontinuation of anticoagulation. (ClinicalTrials.gov number NCT00740883). Figure 1. Cumulative risk of the composite outcome (recurrent VTE or major bleeding) over the entire study period Figure 1. Cumulative risk of the composite outcome (recurrent VTE or major bleeding) over the entire study period Disclosures Couturaud: Astra Zeneka: Co-investigator in clinical trial, Co-investigator in clinical trial Other, Membership on an entity's Board of Directors or advisory committees; Bayer: Co-investigator in clinical trial Other, Membership on an entity's Board of Directors or advisory committees. Sanchez:Bayer: Membership on an entity's Board of Directors or advisory committees. Mismetti:Bayer: Membership on an entity's Board of Directors or advisory committees; pfizer: Membership on an entity's Board of Directors or advisory committees; boerhinger ingelheim: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Jego:Bayer: Membership on an entity's Board of Directors or advisory committees; actelion: Research Funding; GlaxoSmithKline: Research Funding. Parent:Bayer: Membership on an entity's Board of Directors or advisory committees. Lorillon:Astra Zeneka: Membership on an entity's Board of Directors or advisory committees, symposium invitation Other; Sanofi: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Girard:Leo Pharma: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Lacut:Bayer-Healthcare: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Boehringer Ingelheim: Research Funding. Leroyer:Novartis: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Investigator in COPD clinical trials, Investigator in COPD clinical trials Other, Membership on an entity's Board of Directors or advisory committees; Astra Zeneka: Investigator in asthma clinical trials Other, Membership on an entity's Board of Directors or advisory committees. Decousus:Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Meyer:Sanofi-Aventis: Research Funding; LEO Pharma: Research Funding; Bayer: Research Funding; Boehringer Ingelheim: Research Funding. Mottier:Pfizer: Membership on an entity's Board of Directors or advisory committees; bayer: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding.
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Stilgenbauer, Stephan, Barbara F. Eichhorst, Johannes Schetelig, et al. "Venetoclax (ABT-199/GDC-0199) Monotherapy Induces Deep Remissions, Including Complete Remission and Undetectable MRD, in Ultra-High Risk Relapsed/Refractory Chronic Lymphocytic Leukemia with 17p Deletion: Results of the Pivotal International Phase 2 Study." Blood 126, no. 23 (2015): LBA—6—LBA—6. http://dx.doi.org/10.1182/blood.v126.23.lba-6.lba-6.
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Abstract Background: Patients (pts) with CLL harboring 17p deletion [del(17p)] are considered to have very poor prognosis. Venetoclax (VEN) is an orally bioavailable, selective BCL-2 inhibitor that induces apoptosis in CLL cells independent of p53. A phase 1 study of VEN showed high response rates in pts with relapsed/refractory (R/R) CLL, including del(17p) CLL (overall response rate, ORR = 77%). This pivotal phase 2, single-arm, multicenter study evaluated VEN monotherapy in pts with R/R del(17p) CLL. Methods: Pts with R/R del(17p) CLL, assessed in peripheral blood (PB) by a central laboratory ( >7% cells by Vysis FISH probe), commenced VEN once daily with a weekly dose ramp-up schedule (20, 50, 100, 200, 400 mg) over a period of 5 weeks with tumor lysis syndrome (TLS) prophylaxis. Pts were treated with daily 400 mg continuous dosing until disease progression or discontinuation for another reason. The primary objective was to determine the ORR. Responses were determined by both an independent review committee (IRC) and investigators using iwCLL 2008 criteria. Efficacy analyses were pre-specified to occur once pts completed 36 weeks of VEN, had disease progression, or permanently discontinued. Secondary objectives included CR and PR rates, time to first response, duration of response (DoR), progression-free survival (PFS), overall survival (OS), the proportion of pts proceeding to allogeneic stem cell transplant (allo-SCT), and safety. The level of minimal residual disease (MRD) in PB and/or bone marrow (BM) was assessed in a subset of pts by multi-color flow cytometry using iwCLL-recommended sensitivity criteria of <10-4. Results: A total of 107 pts were enrolled in the main cohort (June 2013–June 2014). Median (range) age was 67 (37–85) years; 65% were male. Median number of prior regimens was 2 (1–10); 78 pts (72.9%) had received prior fludarabine (F), 34 (37.4%) were F-refractory, 54 (50.5%) received prior bendamustine (B), and 27 (50%) were B-refractory. 45 pts (42.1%) were high-risk for TLS based on lymph nodes ≥10 cm (or nodes ≥5 cm with ALC ≥25x109/L). All pts but one had del(17p); 60 of 83 pts with available data (72.3%) had mutated TP53 (investigator reported). As of the data cut-off (April 30, 2015), the median time on study was 12.1 (0.03–21.5) months. The primary endpoint of IRC-assessed ORR was 79.4% (95% CI: 70.5%–86.6%). Deep responses included 7.5% CR/CRi and 2.8% nPR, by IRC (Table). Among pts who achieved PR (69.2%, excluding nPR) or non-responders (20.6%) by IRC, 17 pts (15.9%) had no morphological evidence of CLL in the BM. Investigator-assessed ORR is also reported in the Table. 45 pts had an MRD assessment. Notably 18 pts (17% of whole cohort, 21% of responders) had no detectable MRD in the PB; 10 of these were also tested in BM, 6 were MRD-negative. Median time-to-first response was 0.8 months (0.1–8.1); median time to CR/CRi was 8.2 months (3.0–16.3) by IRC. Overall median DoR, PFS, and OS were not reached. The actuarial 12-month PFS and OS rates were 72.0% and 86.7%, respectively (actuarial 12-month DoR rates in Table). 37 pts discontinued treatment: 22 due to PD (9 Richter's transformation), 9 due to AE, 2 withdrew consent, and 1 with non-compliance; 3 pts proceeded to allo-SCT (2 PR, 1 CR by IRC at time of transplant). 11 deaths occurred (≤30 days from last dose of VEN): 7 due to PD, 4 due to AE (stroke, liver derangement, septic shock, and cardio-respiratory insufficiency). 7 additional deaths occurred beyond 30 days from VEN discontinuation (39-328 days) due to PD. Treatment-emergent AEs (all grades) in ≥20% pts were neutropenia (43%), diarrhea (29%), nausea (29%), anemia (27%), and fatigue (22%). Grade 3/4 AEs in ≥10% pts were neutropenia (40%; 25 pts had grade 4), anemia (18%), and thrombocytopenia (15%). 22.4% of pts had neutropenia (any grade) at study entry. Infection ≥ grade 3 occurred in 20% of pts; most common was pneumonia (5%). Laboratory TLS was reported in 5 pts; none had clinical consequences, and all were manageable with electrolyte management and 1-day dose interruption (2 pts). Conclusions: VEN monotherapy achieved a high ORR and sustained remissions with acceptable toxicity in this ultra-high risk pt population with R/R del(17p) CLL. Undetectable MRD was observed in >20% of responders. More than 10% of all pts achieved independently assessed deep responses (CR, CRi, or nPR). Such depths of response have not been previously reported for this population. Disclosures: Stilgenbauer: AbbVie, Amgen, Boehringer-Ingelheim, Celgene, Genentech, Genzyme, Gilead, GSK, Janssen, Mundipharma, Novartis, Pharmacyclics, Hoffman La Roche: Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding. Off Label Use: Venetoclax is an investigational drug and has no label at this time. Eichhorst:AbbVie, Roche: Membership on an entity’s Board of Directors or advisory committees , Research Funding , Speakers Bureau. Schetelig:GSK, Sanofi, Janssen, Neovii: Membership on an entity’s Board of Directors or advisory committees , Research Funding. Coutre:AbbVie: Research Funding ; Gilead: Research Funding ; Pharmacyclics LLC, an AbbVie Company: Consultancy , Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Janssen: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Celgene Corporation: Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Celgene Business Advisory Board: Membership on an entity’s Board of Directors or advisory committees ; Novartis: Research Funding. Seymour:Gilead: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Genentech, Inc.: Membership on an entity’s Board of Directors or advisory committees ; Celgene: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Other: Travel support , Speakers Bureau ; Incyte: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; AbbVie: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Other: Travel support , Research Funding , Speakers Bureau ; Janssen: Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Phebra: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Takeda: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Roche: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Other: Travel support , Research Funding ; Infinity: Honoraria , Membership on an entity’s Board of Directors or advisory committees. Puvvada:Genentech, AbbVie, Spectrum, Janssen and Takeda, Pharmacyclics, Genentech/Roche: Consultancy , Membership on an entity’s Board of Directors or advisory committees , Other: Travel funding for Investigators meeting , Research Funding. Wendtner:Mundipharma: Consultancy , Other: travel grants , Research Funding ; Celege: Consultancy , Other: Travel grants , Research Funding ; Gilead: Consultancy , Other: travel grants , Research Funding ; Glaxo-SmithKline: Consultancy , Other: travel grants , Research Funding ; Janssen-Cilag: Consultancy , Other: travel grants , Research Funding ; Pharmacyclics: Consultancy , Other: travel grants , Research Funding ; Hoffmann-LaRoche: Consultancy , Other: travel grants , Research Funding ; Genentech: Consultancy , Other: travel grants , Research Funding ; AbbVie: Consultancy , Other: travel grants , Research Funding. Roberts:AbbVie and Genentech: Research Funding ; Walter and Eliza Hall Institute of Medical Research: Employment. Jurczak:CELLTRION, Inc,: Research Funding ; Celgene, Eisai, Gilead, Janssen, Mundipharma, Pharmacyclics, Pfizer, Roche, Sandoz –Novartis, Spectrum, Takeda, AbbVie, Morphosys, Janssen, Mundipharma, Sandoz –Novartis, Spectrum, Takeda, Teva, Morphosys: Membership on an entity’s Board of Directors or advisory committees , Research Funding. Mulligan:Sanofi Aventis: Research Funding ; Celgene: Consultancy , Honoraria ; Roche: Consultancy , Honoraria , Research Funding , Speakers Bureau ; Janssen: Consultancy , Honoraria , Speakers Bureau ; AbbVie: Membership on an entity’s Board of Directors or advisory committees. Boettcher:AbbVie: Honoraria , Research Funding ; Celgene: Research Funding ; Roche: Honoraria , Other: travel grants , Research Funding. Mobasher:Genentech, Inc.: Employment ; Roche: Equity Ownership. Zhu:AbbVie: Employment , Equity Ownership. Chyla:AbbVie: Employment , Equity Ownership. Verdugo:AbbVie: Employment , Equity Ownership. Enschede:AbbVie: Employment , Equity Ownership. Cerri:AbbVie: Employment , Equity Ownership. Humerickhouse:AbbVie: Employment , Equity Ownership. Gordon:AbbVie: Employment , Equity Ownership. Hallek:GSK, Genentech: Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Celgene: Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding ; Janssen: Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding ; Mundipharma: Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding ; Boehringher Ingelheim: Honoraria , Other: Speakers Bureau and/or Advisory Boards ; Pharmacyclics: Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding ; Roche: Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding ; Gilead: Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding ; AbbVie: Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding. Wierda:AbbVie, Genentech: Consultancy , Research Funding.
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Szczechowiak, Ewelina. "Doradca zawodowy we współczesnym systemie edukacyjnym." Studia Edukacyjne, no. 56 (March 15, 2020): 253–66. http://dx.doi.org/10.14746/se.2020.56.14.
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Szczechowiak Ewelina, Doradca zawodowy we współczesnym systemie edukacyjnym [Career Advisors in the Contemporary Educational System]. Studia Edukacyjne nr 56, 2020, Poznań 2020, pp. 253-266. Adam Mickiewicz University Press. ISSN 1233-6688. DOI: 10.14746/se.2020.56.14The position of a career advisor in the contemporary educational system is linked to challenges. The situation on the labor market and its changes over the years are crucial for vocational guidance and lifelong learning. Appropriate support from a specialist, parents of an apprentice and teachers can lead to future educational and professional success. Young people think about self-realization, development, and success; they notice that the course of a career in line with their assumptions depends on getting to know their strengths and weaknesses. The main task of career counselors is to help in choosing the further path of education, which is why their role is so important in the life of young people. The article deals with the reality and ideal model of a career advisor and shows the attitude of young people towards a specialist.
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Ribeiro, Vinicius Farias, Adriana Victoria Garibaldi de Hilal, and Marcos Gonçalves Avila. "Advisor gender and advice justification in advice taking." RAUSP Management Journal 55, no. 1 (2019): 4–21. http://dx.doi.org/10.1108/rausp-08-2018-0068.
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Purpose The purpose of this paper is to identify under what circumstances advisor gender and advice justification influence advice taking by managers. Design/methodology/approach The authors designed a quasirational managerial decision experiment with both analytic and intuitive cues. The design was a 2 × 2 between-subjects factorial, in which gender (male/female) and advice justification (intuitive/analytic) were crossed. The experiment involved two independent samples, taken from Amazon Mechanical Turk workers and Brazilian professionals. Findings Results suggest that, in general, analytic justification is more valued than intuitive justification. The findings also infer that depending on the advisees’ sample and providing that advice justification is analytic, quasirational scenarios seem to favor male advisors (MTurk sample) or both male and female advisors with “male values” (professional sample), as analysis is traditionally considered a “male value.” Practical implications Analytic justification will likely lead to more advice utilization in quasirational managerial situations, as it may act as a safeguard for the accuracy of the offered advice. Social implications The results might signal an ongoing, but slow, process leading to the mitigation of gender stereotypes, considering that the male gender stereotype was active in the MTurk sample, but not in the professional one. Originality/value This study contributes to the advice-taking research field by showing the interplay between advisor gender and advice justification in a quasirational managerial decision setting with both analytic and intuitive cues. In advice-taking literature, observations are usually collected from students. However, as this study focused on managerial decisions, the authors collected independent samples from MTurk workers and Brazilian professionals.
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Wellborn, Beatrice. "Developing an Advisor's Web Page." NACADA Journal 18, no. 1 (1998): 58–60. http://dx.doi.org/10.12930/0271-9517-18.1.58.
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A Web page provides an indispensable resource to advisees. Advisors may include content unique to the needs of their specific advisee populations, and the hyperactive linkages contained on a page can lead to other important academic and job-related resources. This article provides suggestions about how to start Web page development and where one may find examples of advising related sites. A brief outline of possible content is suggested.
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Mateos, Maria-Victoria, Meletios A. Dimopoulos, Michele Cavo, et al. "Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE)." Blood 130, Suppl_1 (2017): LBA—4—LBA—4. http://dx.doi.org/10.1182/blood.v130.suppl_1.lba-4.lba-4.
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Abstract Introduction VMP is a standard of care (SOC) for transplant ineligible NDMM. Daratumumab (D), a human IgGκ anti-CD38 monoclonal antibody with a direct on-tumor and multifaceted immunomodulatory mechanism of action significantly improves PFS and depth of response in combination with SOC in relapsed MM. Treatment-naïve pts may benefit greatly with the addition of D to SOC regimens. Here we report the results from the ALCYONE study, where D is added to VMP in transplant ineligible NDMM. Methods Pts ≥65 years or otherwise ineligible for high-dose chemotherapy with autologous stem cell transplantation were randomized 1:1 to VMP ± D and stratified by International Staging System (ISS [I, II, III]), region (Europe vs other) and age (&lt;75 vs ≥75 years). All pts received up to a maximum of nine 6-week cycles of VMP. V: 1.3 mg/m2 SC on Days 1, 4, 8, 11, 22, 25, 29, 32 (Cycle 1) and Days 1, 8, 22, and 29 (Cycles 2-9); M: 9 mg/m2 PO and P: 60 mg/m2 PO on Days 1-4 (Cycles 1-9). In the D-VMP arm, D was given at 16 mg/kg IV QW for Cycle 1, Q3W for Cycles 2-9, and Q4W for Cycles 10+ (post VMP-treatment phase) until disease progression. The primary endpoint was PFS. Key secondary endpoints included overall response rate (ORR), rate of very good partial response (VGPR) or better, rate of complete response (CR) or better, minimal residual disease (MRD)-negativity rate (10-5 threshold, Adaptive clonoSEQ® Assay), overall survival (OS), and safety. Results Of 706 pts randomized (350 D-VMP; 356 VMP), median (range) age was 71 (40-93) years; 29.9% were ≥75 years; 46.3% were male. 74.9% of pts had ECOG scores ≥1, and 19.3%, 42.4%, and 38.4% were ISS stage I, II, and III, respectively. Of 616 pts evaluable for FISH/karyotyping cytogenetic analysis, 84.1% and 15.9% were standard and high risk (positive for del17p, t[14;16], t[4;14]), respectively. At the timepoint of the prespecified analysis after 231 PFS events on 12 June 2017, pts had received a median (range) of 12 (1-24) vs 9 (1-9) treatment cycles for D-VMP vs VMP, respectively. 80% of pts in the D-VMP arm completed 9 treatment cycles of VMP vs 62% of pts in the VMP arm. Median (range) cumulative bortezomib doses were 46.9 (1.3-55.3) mg/m2 vs 42.2 (2.6-55.0) mg/m2 for D-VMP vs VMP, respectively. At a median follow-up of 16.5 months, the hazard ratio for PFS (D-VMP vs VMP) was 0.50 (95% confidence interval, 0.38-0.65, P &lt;0.0001), representing a 50% reduction in the risk of progression or death in pts treated with D-VMP (Figure). Median PFS was not reached vs 18.1 months for D-VMP vs VMP. The PFS treatment benefit of D-VMP vs VMP was consistent across all pre-specified subgroups, including age ≥75 years, ISS stage III, and high-risk cytogenetics. ORR (90.9% vs 73.9%), ≥VGPR (71.1% vs 49.7%), ≥CR (42.6% vs 24.4%) and MRD-negativity rate (22.3% vs 6.2%) were significantly higher for D-VMP vs VMP (all P &lt; 0.0001; Table). OS data were immature after 93 deaths (45 vs 48 deaths for D-VMP vs VMP). The most common (≥20%) all-grade treatment emergent adverse events (TEAE; D-VMP/VMP) were neutropenia (49.7%/52.5%), thrombocytopenia (48.8%/53.7%), anemia (28.0%/37.6%), peripheral sensory neuropathy (28.3%/34.2%), upper respiratory tract infection (26.3%/13.8%), diarrhea (23.7%/24.6%), pyrexia (23.1%/20.9%), and nausea (20.8%/21.5%). Most common (≥10%) grade 3/4 TEAEs (D-VMP/VMP) were neutropenia (39.9%/38.7%), thrombocytopenia (34.4%/37.6%), anemia (15.9%/19.8%), and pneumonia (11.3%/4.0%). Only 1 pt in each arm discontinued treatment due to pneumonia. The rates of grade 3/4 infections were 23.1% vs 14.7% and treatment discontinuations due to infections were 0.9% vs 1.4% for D-VMP vs VMP. D-associated infusion-related reactions (27.7%) mostly were grade 1/2 (grade 3/4, 4.3%/0.6%) and most (92.7%) occurred during the first infusion. Tumor lysis syndrome occurred in &lt;1% of pts in each arm. Second primary malignancy occurred in 2.3% vs 2.5% pts in D-VMP vs VMP. Conclusion The combination of D with VMP in transplant ineligible NDMM pts doubled the PFS (HR 0.50), which was driven by more pts achieving deep responses, including significantly higher ≥CR rate and tripling of the MRD-negativity rate. No new safety signals were observed when combining D with VMP. Three phase 3 studies have now demonstrated a consistent doubling of PFS and more than threefold increase in MRD-negativity rate when combining D with SOC regimens. These results support the use of a D-based combination, D-VMP, in transplant ineligible NDMM. Disclosures Mateos: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Dimopoulos:Novartis: Consultancy, Honoraria; Genesis Pharma: Research Funding; Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology: Consultancy, Honoraria, Other: Advisory Committee: Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology. Cavo:Celgene:: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria. Suzuki:Bristol Myers Squibb: Honoraria; Novarltis: Honoraria; Celgene: Honoraria; Ono Pharmaceuticals: Honoraria; Fujimoto: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Sanofi: Honoraria. Jakubowiak:Amgen Inc., BMS, Celgene, Janssen, Karypharm, Millennium-Takeda, Sanofi, SkylineDX: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; University of Chicago: Employment. Knop:Bristol-Myers Squibb Germany: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Germany: Honoraria, Membership on an entity's Board of Directors or advisory committees; AMGEN Germany: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Janssen Germany: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene Germany: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene Germany: Honoraria, Membership on an entity's Board of Directors or advisory committees. Doyen:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lucio:Janssen: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Roche: Consultancy. Cook:Amgen: Honoraria, Other: Travel support; Takeda: Honoraria; Myeloma UK: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria; Myeloma UK: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria; Janssen: Honoraria, Other: Travel support, Research Funding; Celgene: Honoraria, Other: Travel support, Research Funding. Garg:Janssen: Other: travel support, Research Funding, Speakers Bureau; Takeda: Other: travel support; Novartis: Other: travel support, Research Funding. Chiu:Janssen: Employment. Wang:Janssen: Employment. Carson:Janssen: Employment. Crist:Janssen: Employment. Deraedt:Janssen: Employment. Nguyen:Janssen: Employment. Qi:Janssen: Employment; Johnson & Johnson, LLC: Equity Ownership. San-Miguel:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cilag: Consultancy; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees.
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Stadtmauer, Edward A., Marcelo C. Pasquini, Beth Blackwell, et al. "Comparison of Autologous Hematopoietic Cell Transplant (autoHCT), Bortezomib, Lenalidomide (Len) and Dexamethasone (RVD) Consolidation with Len Maintenance (ACM), Tandem Autohct with Len Maintenance (TAM) and Autohct with Len Maintenance (AM) for up-Front Treatment of Patients with Multiple Myeloma (MM): Primary Results from the Randomized Phase III Trial of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0702 - StaMINA Trial)." Blood 128, no. 22 (2016): LBA—1—LBA—1. http://dx.doi.org/10.1182/blood.v128.22.lba-1.lba-1.
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Abstract Background: Len maintenance after autoHCT has improved progression-free (PFS) and overall survival (OS). However, the role of additional interventions after autoHCT such as tandem autoHCT or triple therapy consolidation remains to be determined. Methods: This is a phase III clinical trial (NCT#01109004) of transplant-eligible patients (pts) with symptomatic MM <71 years of age within 12 months of initiating therapy and without prior progression who were randomly assigned 1:1:1 to receive melphalan 200mg/m2 autoHCT and 4 cycles of RVD consolidation (lenalidomide 15mg daily days 1-14, dexamethasone 40mg day 1,8 and 15, and bortezomib 1.3mg/m2 days 1,4,8 and 11 every 21 days) (ACM), versus tandem melphalan 200mg/m2 autoHCT (TAM) or versus a single autoHCT (AM). Randomization was stratified by disease risk (cytogenetic abnormalities - del13q by karyotype, del17q, t(4;14), t(14;16), t(14;20) and hypodyploid; or high beta-2 microglobulin) and center. All arms included Len maintenance (at maximum tolerated dose of 5 to 15 mg orally daily until progression) with dose modifications for toxicities. All patients were reviewed centrally for eligibility, response and progression. The primary objective was to compare 38-month PFS of the three arms. The events for PFS included progression, non-protocol anti-myeloma therapy, or death. Comparisons between treatment groups were based on pairwise log-rank tests stratified on disease risk, with significance levels adjusted for the 3 pairwise comparisons and for interim analyses. In calculating the cumulative incidence of progression, the events were progression or non-protocol anti-myeloma therapy, and death was a competing risk. Results: From June 2010 to November 2013, 758 pts (ACM, N=254; TAM, N=247; AM, N=257) aged 20-70 years (median 57y) were enrolled. Of those enrolled, 24% were classified as high risk. Non-compliance rates following the first autoHCT were 12%, 32% and 5% for ACM, TAM and AM, respectively. Median available follow up from randomization was 38 months. Follow-up is continuing through January 2017. 38-month estimated probabilities for PFS were 57% (95% CI: 50-63%), 56% (95% CI: 49-63%) and 52% (95% CI: 45-59%) for ACM, TAM and AM, respectively (ACM vs TAM p=0.75, ACM vs AM p=0.21, TAM vs AM p=0.37). Corresponding probabilities of OS were 86% (95% CI: 80-90%), 82% (95%CI: 76-87%) and 83% (95% CI: 78-88%). Median OS has not been reached. Cumulative incidences of disease progression at 38 months were 42% (95% CI: 36-48%), 42% (95% CI: 35-48%) and 47% (95% CI: 40-54%) for the ACM, TAM and AM arms, respectively. There were 39 cases of second primary malignancy (SPM) reported in 36 participants and the cumulative incidences for first SPM were 6.0% (95% CI: 3.4-9.6%), 5.9% (95% CI: 3.3-9.6%) and 4.0% (95% CI: 1.9-7.2%) for the ACM, TAM, and AM, respectively. Conclusions: The primary results of the largest randomized US transplant trial in MM demonstrated comparable PFS and OS. The addition of RVD consolidation or a second auto-HCT was not superior to a single auto HCT followed by Len maintenance in the upfront treatment of MM. A long term follow-up trial to track outcomes in these patients is ongoing. Disclosures Stadtmauer: Amgen: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Janssen: Consultancy. Pasquini:Atara: Other: travel reimbursement for a meeting; Baxalta: Honoraria, Membership on an entity's Board of Directors or advisory committees. Efebera:Millennium/Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria. Ganguly:Onyx: Speakers Bureau; Seattle Genetics: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees. Giralt:Celgene: Consultancy; Millenium/Takeda: Consultancy. Hari:Celgene: Consultancy; Millennium/Takeda: Consultancy. McCarthy:Celgene: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Millennium/Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; The Binding Site: Consultancy, Honoraria. Qazilbash:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Shah:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Membership on an entity's Board of Directors or advisory committees. Vesole:Takeda: Speakers Bureau; Celgene: Speakers Bureau. Vij:Millennium/Takeda: Consultancy; Celgene: Consultancy. Vogl:Celgene: Consultancy; Millennium/Takeda: Consultancy, Research Funding. Somlo:PUMA: Consultancy; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium/Takeda: Speakers Bureau; Astra Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees. Krishnan:Celgene: Consultancy, Speakers Bureau; Millennium/Takeda: Consultancy, Speakers Bureau; Onyx: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau.
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Lee, Agnes Y. Y., Pieter W. Kamphuisen, Guy Meyer, et al. "A Randomized Trial of Long-Term Tinzaparin, a Low Molecular Weight Heparin (LMWH), Versus Warfarin for Treatment of Acute Venous Thromboembolism (VTE) in Cancer Patients - the CATCH Study." Blood 124, no. 21 (2014): LBA—2—LBA—2. http://dx.doi.org/10.1182/blood.v124.21.lba-2.lba-2.
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Abstract Background Patients with cancer and VTE have a substantial risk of recurrent VTE. LMWH reduces the risk of symptomatic, recurrent VTE compared with warfarin and is recommended as the preferred anticoagulant by consensus guidelines. However, the evidence is based largely on a single, open-label randomized trial (CLOT; Lee et al NEJM 2003). Warfarin is still often used for the treatment of VTE in cancer patients worldwide. Methods The primary objective of this randomized, open-label, multicenter, Phase III trial (CATCH; NCT01130025) was to assess the efficacy of tinzaparin in preventing recurrent VTE in patients with active cancer and acute, symptomatic proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Patients were randomized (stratified by geographic region, tumor characteristic [distant metastasis, no distant metastasis, hematological malignancy] and history of VTE) to receive tinzaparin 175 IU/kg once daily for 6 months or initial tinzaparin 175 IU/kg once daily for 510 days overlapped and followed by dose-adjusted warfarin (target INR 2.03.0) for 6 months. The primary efficacy outcome was time to recurrent VTE verified by objective, standard imaging and blinded central adjudication; this was a composite primary endpoint that included symptomatic DVT and/or PE, incidental proximal DVT and/or PE and fatal PE. The primary safety endpoint was incidence of major bleeding. All patients were followed up to 6 months or death, whichever came sooner. Blinded central adjudication was also performed for all bleeding events and causes of death. A proportional hazards model for competing risks was applied to all randomized patients, treating all non-VTE-related deaths as competing events. An independent Data Safety Monitoring Board reviewed safety data at regular intervals. Results Nine hundred patients were included from 165 sites in 32 countries across 5 continents. Of these, 449 were randomized to tinzaparin and 451 to warfarin. Mean age was 59 years (range 1889); 59% female. A total of 77% of patients had a baseline ECOG performance status (PS) of 01 and 23% had a PS of 2. The most common primary tumor sites were gynecologic (23%), colorectal (13%), lung (12%), breast (9%); 10% had hematological malignancies. At the time of randomization, metastatic disease was present in 55% of patients and 44% had received prior cancer treatment (chemotherapy, surgery and/or radiation). Time-in-therapeutic range was 47% in the warfarin arm, with 27% above and 26% below the range. Over the 6-month trial period, 31 patients (6.9%) in the tinzaparin arm experienced recurrent VTE compared with 45 (10%) in the warfarin arm (hazard ratio [HR] 0.65 [95% CI 0.411.03; P=0.07]) (see figure). There were 2 patients with incidental VTE, both were in the warfarin arm. Symptomatic non-fatal DVT occurred in 12 patients (2.7%) in the tinzaparin arm and 24 (5.3%) in the warfarin arm (HR 0.48 [95% CI 0.240.96]; P=0.04). Symptomatic non-fatal PE occurred in 3 patients in the tinzaparin arm and 2 in the warfarin arm; fatal PE occurred in 17 (3.8%) patients in each arm (HR 0.96 [95% CI 0.491.88]; P=0.90). There was no difference in the incidence of major bleeding events (n=13 [2.9%] in the tinzaparin arm and 12 [2.7%] in the warfarin arm), but significantly fewer patients experienced clinically relevant non-major bleeding with tinzaparin than warfarin (50 [11%] and 73 [16%] patients, respectively; P=0.03). No difference in mortality was seen with 6-month survival rates of 59% and 60%, respectively. Conclusions In cancer patients with symptomatic VTE, tinzaparin lowered the risk of recurrent VTE compared with warfarin, with a significant reduction in symptomatic DVT and clinically relevant non-major bleeding. No difference in major bleeding or overall mortality was observed. Figure. Cumulative incidence of recurrent VTE in the tinzaparin and warfarin groups. Figure. Cumulative incidence of recurrent VTE in the tinzaparin and warfarin groups. Disclosures Lee: Bayer: Advisory Boards Other, Honoraria; Bristol-Myers Squibb: Advisory Boards, Advisory Boards Other, Research Funding; Boehringer Ingelheim: Honoraria; Daiichi-Sankyo: Advisory Boards, Advisory Boards Other; Eisai: Research Funding; LEO Pharma: Advisory Boards Other; Pfizer: Advisory Boards Other, Honoraria, Research Funding; Sanofi-Aventis: Advisory Boards, Advisory Boards Other; Avivia: Advisory Boards, Advisory Boards Other. Kamphuisen:LEO Pharma: Honoraria, Research Funding. Meyer:Bayer: Research Funding; Boehringer Ingelheim: Research Funding; LEO Pharma: Research Funding; Sanofi-Aventis: Research Funding. Janas:LEO Pharma: Employment. Jarner:LEO Pharma: Employment. Khorana:LEO Pharma: Honoraria, Research Funding.
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Boychuk, Petro M., Olha L. Fast, Olha P. Shevchuk, Tetiana V. Horobets, and Vasyl A. Shkoba. "The Impact of the Academic Advising Style on the Development of an Academic Integrity Culture among Future PhD Candidates." International Journal of Learning, Teaching and Educational Research 20, no. 4 (2021): 302–19. http://dx.doi.org/10.26803/ijlter.20.4.16.
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Our research studied the impact of academic advising style on the development of a culture of academic integrity among PhD candidates. The study involved 52 postgraduate students and their 52 academic advisors. The results obtained were analyzed through general scientific methods. We used a closed-ended questionnaire to gather data from academic advisors, open-ended questions for postgraduate students, mathematical data processing techniques, and the Statistica software package to interpret data. The empirical data indicates that a pastoral academic advising style was applied by 17,3% of advisors, a laissez-faire style by 11,5%, a contractual style by 40,4%, and a directorial style by 30,8% of advisors in this study. Correlating these results with data on postgraduate students’ level of academic integrity culture lead to the conclusion that the contractual style of academic advising could be regarded as the most beneficial for raising the level of academic integrity culture of postgraduate students (33,3% of students of advisors with this style had a high level of academic integrity culture). The weakest style for improving the level of academic integrity culture of students is the pastoral style (11,1%). Moreover, it is obvious that most academic advisors (40,4%) use the mutually beneficial contractual style. The quantitative increase of advising style indicators corresponding to the contractual type entails higher values for students’ academic integrity culture. The relationship between advising style and level of academic integrity culture is not linear, and we cannot argue that an academic advisor with a contractual leadership style adheres to all the desirable principles of academic integrity culture. Further investigations are required if more specific and diversified conclusions are to be made. Furthermore, we should take into account that other members of the academic staff also have an impact on the formation and improvement of the academic integrity culture of postgraduate students.
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Neelapu, Sattva S., Frederick L. Locke, Nancy L. Bartlett, et al. "Kte-C19 (anti-CD19 CAR T Cells) Induces Complete Remissions in Patients with Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Results from the Pivotal Phase 2 Zuma-1." Blood 128, no. 22 (2016): LBA—6—LBA—6. http://dx.doi.org/10.1182/blood.v128.22.lba-6.lba-6.
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Abstract Background: Patients (pts) with refractory aggressive non-Hodgkin lymphoma (NHL) have poor outcomes with currently available therapies, with a complete response (CR) rate of 8%, a partial response (PR) rate of 18%, and median overall survival (OS) of 6.6 months (mo) as demonstrated in the 635 pt SCHOLAR-1 meta-analysis (Crump, ASCO 2016; abstract 7516). ZUMA-1 is the first multicenter trial of anti-CD19 chimeric antigen receptor (CAR) T cells in refractory, aggressive NHL (NCT02348216). The phase 1 portion of ZUMA-1 showed ongoing CRs at 12+ mos in 43% of pts (Locke, ESMO 2016; abstract 1048O). The pivotal phase 2 portion of ZUMA-1 comprises 2 cohorts based on tumor type: DLBCL (cohort 1) and primary mediastinal B-cell lymphoma or transformed follicular lymphoma (cohort 2). Here, we present results of a prespecified interim analysis from cohort 1. Methods: Pts received a target dose of 2 × 106 anti-CD19 CAR T cells/kg after a low-dose conditioning regimen of cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) daily for 3 days. The primary endpoint is objective response rate (ORR) per 2007 IWG criteria. Key secondary endpoints include duration of response, frequency of adverse events (AEs), and levels of CAR T cells and serum cytokines. Key inclusion criteria include age ≥18 years, ECOG performance status (PS) 0-1, and refractory disease defined as progressive disease or stable disease as best response to last line of therapy, or disease progression ≤12 mos after autologous stem cell transplant (ASCT). Pts must have received a prior anti-CD20 antibody and an anthracycline-containing regimen. A prespecified interim analysis was to be conducted to determine early efficacy with a nominal alpha level of 0.017 in 50 treated pts in cohort 1 with a minimum follow-up of 3 mos. Results: In total, 111 pts from 22 institutions were enrolled and leukapheresed, and 101 pts received KTE-C19. As of August 24, 2016, 51 pts in cohort 1 were eligible for analysis. Median age was 58 years (range, 25-76), 73% were male, 71% had ECOG PS 1, 78% were refractory to ≥2 lines of therapy, 20% relapsed ≤12 mos of ASCT, and 61% were treated with ≥3 lines of prior therapy. KTE-C19 was successfully manufactured in 99% of pts enrolled. Average turnaround time from apheresis to receipt of KTE-C19 at the clinical site was 17.4 days. With an ORR of 76%, the study met the primary endpoint (P<0.0001; exact binomial test comparing observed ORR to a historical control assumption of 20%), with 47% CRs and 29% PRs. 92% of responses occurred within the 1st mo, and 39% of pts had ongoing responses (CR in 33%) at 3 mos. Responses were seen across key covariates, including refractory subgroup (refractory to chemotherapy=76%, relapse post ASCT=80%). Kaplan-Meier estimates of progression-free survival at 1 and 3 mos were 92% and 56%, respectively. The most common grade ≥3 treatment-emergent AEs were neutropenia (67%), anemia (39%), thrombocytopenia (29%), febrile neutropenia (27%), and encephalopathy (24%). Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in 20% and 29% of pts, respectively. There was 1 grade 5 KTE-C19-related event of hemophagocytic lymphohistiocytosis. CAR T cells expanded within 14 days of KTE-C19 infusion, and peak expansion was associated with ongoing response at mo 3 (P=0.008). Pts who developed grade ≥3 neurological events had increased serum levels of IL-15 (P=0.0002), IL-6 (P=0.003); IL-10 (P=0.009) and IP-10 (P=0.0003). Cytokines/chemokines returned to baseline levels in most pts by day 28. Data from 93 pts with at least 1 mo of follow-up at the data cutoff will be presented. Conclusions: ZUMA-1 is the first reported multicenter trial of CAR T cell therapy in pts with refractory aggressive NHL. KTE-C19 induced a nearly 6-fold higher CR rate compared to historical outcomes in SCHOLAR-1. Efficacy strongly associated with peak CAR T levels. Central manufacturing, logistics, and AE management were successfully implemented across 22 sites, most with no prior CAR T therapy experience. Results from cohort 2 of ZUMA-1 are also presented (Abstract #998). KTE-C19 demonstrated significant clinical benefit in pts with no curative treatment options. Supported in part by funding from The Leukemia & Lymphoma Society Therapy Acceleration Program®. Drs Neelapu and Locke contributed equally to this study. Disclosures Neelapu: Kite Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding. Locke:Kite: Membership on an entity's Board of Directors or advisory committees. Miklos:pharmacyclics: Research Funding; Kite Pharma: Research Funding; Roche: Research Funding; Novartis: Research Funding. Jacobson:Kite: Membership on an entity's Board of Directors or advisory committees. Siddiqi:Pharmacyclics: Speakers Bureau; Janssen: Speakers Bureau; Seattle Genetics: Speakers Bureau. Lin:Mayo Clinic: Employment; Janssen: Research Funding. Timmerman:Bristol-Myers Squibb, Kite Pharma, Valor Biopharmaceuticals, Janssen: Research Funding; Seattle Genetics, Genmab, Celgene: Consultancy, Honoraria. Goy:COTA: Membership on an entity's Board of Directors or advisory committees; Janssen/Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Research funding for clinical trials through institution, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Research funding for clinical trials through institution; Acerta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Other: Research funding for clinical trials through institution. Smith:Abbvie: Research Funding; Celgene: Honoraria; Spectrum: Honoraria; Genentech: Honoraria. Deol:Jazz Pharmaceuticals: Consultancy. Avivi:Tel Aviv Sourasky Medical center: Consultancy, Other: consultancy to :BMS Roche. Westin:Genentech: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; ProNAi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Chavez:Janssen: Speakers Bureau. Levy:Kite Pharma: Consultancy; Five Prime Therapeutics: Consultancy; Innate Pharma: Consultancy; Beigene: Consultancy; Corvus: Consultancy; Dynavax: Research Funding; Pharmacyclics: Research Funding. Reagan:Seattle Genetics: Research Funding. Bot:Kite Pharma: Employment, Equity Ownership. Rossi:Kite Pharma: Employment, Equity Ownership. Navale:Kite Pharma: Employment, Equity Ownership. Jiang:Kite Pharma: Employment, Equity Ownership. Aycock:Kite Pharma: Employment, Equity Ownership. Elias:Kite: Employment, Equity Ownership. Wiezorek:Kite Pharma: Employment, Equity Ownership. Go:Kite Pharma: Employment, Equity Ownership.
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Seymour, John F., Thomas J. Kipps, Barbara F. Eichhorst, et al. "Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia - Results from Pre-Planned Interim Analysis of the Randomized Phase 3 Murano Study." Blood 130, Suppl_1 (2017): LBA—2—LBA—2. http://dx.doi.org/10.1182/blood.v130.suppl_1.lba-2.lba-2.
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Abstract Introduction Venetoclax (V), an orally administered, highly selective, potent BCL-2 inhibitor, induces high ORR when given as monotherapy to pts with relapsed/refractory (R/R) CLL, including high-risk populations, e.g. del(17p). V is also well tolerated when combined with rituximab (R) and achieves improved CR rates and minimal residual disease negativity (MRD-). Here, we provide first released data from the primary analysis of MURANO (NCT02005471), the first Phase 3 study of V in pts with R/R CLL, which assessed efficacy/safety of VR vs standard chemoimmunotherapy, bendamustine (B) + rituximab (BR). Methods Eligibility for this open-label, randomized, Phase 3 study included R/R CLL requiring treatment (iwCLL guidelines), 1-3 prior lines of therapy (including ≥1 chemo-containing) and ECOG PS ≤1. Prior B was allowed provided response duration was ≥24 mo. Pts were randomized (1:1) to VR or BR. Stratification factors were del(17p), responsiveness to prior therapy and geographic region. In the VR arm, a 4- or 5-wk graduated dose ramp-up of V from 20-400 mg daily was used to mitigate potential tumor lysis syndrome (TLS) risk. Beginning at Wk 6, R was then given monthly for six 28-day cycles (IV 375 mg/m2 first dose, then 500 mg/m2) in combination with V daily. Pts continued with V 400 mg for a maximum of 2 yr or until disease progression (whichever first). In the BR arm, pts were given B (IV 70 mg/m2) on Days 1 and 2 of each of six 28-day cycles in combination with R using same R dosing schedule. MRD was centrally assessed by ASO-PCR and/or flow cytometry in peripheral blood at screening, Mo. 4 and 9, and 3-monthly follow-up visits. The primary endpoint was investigator (INV)-assessed PFS. An interim analysis was preplanned at ~140 INV-assessed PFS events. On data review, an Independent Data Monitoring Committee recommended study arms to be unblinded to the sponsor as pre-specified statistical boundaries for early stopping were crossed for PFS in favor of VR. Results 389 pts were enrolled in VR (n=194) and BR (n=195) arms, which were well balanced: median (range) age, 64.5 (28-83) vs 66.0 (22-85) yr; 1 prior therapy, 57.2% vs 60.0%; fludarabine refractory, 14.1% vs 15.5%; del(17p), 26.6% vs 27.2%. At data cut-off (8 May 2017; median follow-up, 23.8 mo. [range 0.0-37.4]), INV-assessed PFS was superior for VR vs BR with HR 0.17, 95% CI 0.11-0.25, P&lt;0.0001; median not reached vs 17.0 mo. (Fig 1). 24-mo. PFS estimates were 84.9% vs 36.3%, respectively. Consistent treatment effects on PFS were observed in all subgroups assessed (Fig 2). With HR 0.19, 95% CI 0.13-0.28, P&lt;0.0001, Independent Review Committee-assessed PFS showed a similar magnitude of benefit. Key secondary efficacy endpoints showed consistent improvements for VR vs BR including a notable improvement in OS (HR 0.48, 95% CI 0.25-0.90). INV-assessed ORR was 93.3% with VR vs 67.7% with BR (Δ=25.6%, 95% CI 17.9-33.3%); CR/CRi was achieved in 26.8% vs 8.2% of pts, respectively (Table 1). Higher peripheral blood MRD- rates attained at any time were seen with VR vs BR (83.5% vs 23.1%; Δ=60.4%, 95% CI 52.3-68.6%) by ITT analysis. MRD negativity was more durable in the VR arm. Consistent with known safety profiles of the regimens, Grade 3-4 neutropenia was higher in VR arm but there was no increase in febrile neutropenia or Grade 3-4 infection (Table 2). There were 6 (3.1 %) and 2 (1.1%) Grade ≥3 AEs of TLS reported for VR and BR, respectively; one clinical TLS event in each arm (a Grade 4 acute renal failure in BR, transient increase in creatinine in VR; VR event occurred on an earlier 4-week ramp-up schedule). Richter transformation was confirmed in 6 pts and 5 pts for VR vs BR, respectively. AEs leading to death were seen in 5.2% vs 5.9% of pts. Median relative V dose intensity was 97% of protocol-specified drug exposure. Conclusion The primary analysis of MURANO, the first Phase 3 study of V in R/R CLL, shows a profound improvement in PFS vs standard BR chemoimmunotherapy, with consistent effects in all-risk subsets. Key secondary endpoints, including OS, ORR and CR rate, also showed consistent improvements with remarkable rates of peripheral blood MRD- that exceed those previously attained in treatment of R/R CLL. This enhanced disease control was achieved in a multinational setting with an acceptable safety profile, without significant TLS, demonstrating that treatment with VR resulted in outcomes superior to that of BR for pts with R/R CLL. Disclosures Seymour: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Morphosys: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sunesis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kipps:Celgene: Consultancy; Oncternal: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding. Eichhorst:Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding. Hillmen:Celgene: Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria. D'Rozario:Roche: Consultancy. Assouline:Lundbeck: Other: Advisory Board; Paladin: Speakers Bureau; Pfizer: Speakers Bureau; Bristol Myer Squibb: Speakers Bureau; Roche Canada: Consultancy. Owen:AstraZeneca: Honoraria; AbbVie: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Lundbeck: Honoraria; Roche: Honoraria; Merck: Honoraria. Gerecitano:Merck: Consultancy; Mass Medical International: Consultancy; Incyte: Consultancy; Arcus Medica: Consultancy; Aratana: Consultancy; Bayer: Consultancy; Genentech: Consultancy; Samus Therapeutics: Consultancy; Abbvie: Consultancy; Gilead: Consultancy; Orexo: Consultancy. Robak:AbbVie: Honoraria, Research Funding; Akari Therapeutics Plc: Honoraria, Research Funding; Roche: Honoraria, Research Funding. De la Serna:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jaeger:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria; Amgen: Honoraria; AOP Orphan: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; GSK: Honoraria; Infinity: Honoraria; Millennium: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Bioverativ: Honoraria, Research Funding. Cartron:Gilead: Honoraria; Janssen: Honoraria; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Sanofi: Honoraria. Montillo:Novartis: Honoraria; Roche: Research Funding; Abbvie: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Humerickhouse:AbbVie: Employment, Equity Ownership. Punnoose:Genentech: Employment. Li:Genentech: Employment. Boyer:Roche: Employment. Humphrey:F-Hoffmann-La Roche: Employment, Equity Ownership. Mobasher:Roche: Equity Ownership; Genentech: Employment. Kater:Roche: Consultancy; Acerta/Astra Zeneca: Consultancy, Research Funding; Roche/Genentech: Research Funding; Abbvie: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Research Funding; Sandoz: Consultancy.
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St.Cyr Brisini, Kellie, and Denise Haunani Solomon. "Building Expertise: Effects of Experience Claims on Responses to Advice." Journal of Language and Social Psychology 39, no. 3 (2020): 375–96. http://dx.doi.org/10.1177/0261927x20911978.
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People place more value on advice from others whom they view as expert; however, the ways in which advisors might increase perceptions of their expertise through language choice remains unclear. This article examines a married partner’s ability to influence perceptions of their expertise, and consequent advice outcomes, by making explicit claims about past experience with a problem. Two experimental studies tested the effects of experience claims across work versus family problem contexts and examined dimensions of relational communication as mediators. Findings demonstrated that experience claims have the potential to affect evaluations of the spouse’s expertise and evaluations of advice; however, this effect varied based on problem context. Results suggested that statements about previous experience with work problems may improve advice outcomes, whereas experience claims in the context of family problems lead to less positive perceptions of advice. Perceived advisor empathy mediated the negative association between experience claims and advice outcomes.
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MAHONEY, DIANA. "Lead in Artificial Turf Brings CDC Advisory." Pediatric News 42, no. 7 (2008): 4. http://dx.doi.org/10.1016/s0031-398x(08)70293-5.
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Price, Anna. "Academic Advisors in Athletics Lead the Way." NACADA Journal 14, no. 2 (1994): 66–67. http://dx.doi.org/10.12930/0271-9517-14.2.66.
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Dimopoulos, Meletios A., Martha Q. Lacy, Philippe Moreau, et al. "Pomalidomide in Combination with Low-Dose Dexamethasone: Demonstrates a Significant Progression Free Survival and Overall Survival Advantage, in Relapsed/Refractory MM: A Phase 3, Multicenter, Randomized, Open-Label Study." Blood 120, no. 21 (2012): LBA—6—LBA—6. http://dx.doi.org/10.1182/blood.v120.21.lba-6.lba-6.
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Abstract Abstract LBA-6 Background: Multiple myeloma (MM) patients who have become refractory to bortezomib (BORT) and refractory or otherwise ineligible for thalidomide or lenalidomide (LEN) have a poor prognosis, with a median overall survival (OS) of 9 months (Kumar. Leukemia. 2012). There is no standard treatment available for these patients. Pomalidomide (POM) is a novel immunomodulatory drug that has shown activity in LEN- and BORT-refractory patients (Vij. ASCO 2012). MM-003 is an open-label, multicenter, phase 3 trial designed to compare the efficacy and safety of POM + low-dose dexamethasone (LoDEX) vs high-dose dexamethasone (HiDEX) in a population of patients who are refractory to both LEN and BORT. Here we present the final progression-free survival (PFS) and interim OS analysis of MM-003. Methods: Eligible patients with primary refractory or relapsed and refractory disease were enrolled. All patients with documented disease progression during treatment or within 60 days of completing their last myeloma therapy (including ≥ 2 consecutive cycles of LEN and BORT either alone or in combination), were randomized 2:1 to receive either POM + LoDEX (arm A) or HiDEX alone (arm B). Patients progressing on HiDEX had the opportunity to receive POM in the companion trial, MM-003C. Patients in arm A received POM 4 mg on days 1–21 and DEX 40 mg (20 mg for patients > 75 years of age) on days 1, 8, 15, and 22 in a 28-day cycle. Patients in arm B received DEX 40 mg (20 mg for patients > 75 years of age) on days 1–4, 9–12, and 17–20 in a 28-day cycle. Treatment was continued until progressive disease or unacceptable toxicity. Patients were stratified by age (≤ 75 vs > 75 years), disease population (refractory vs refractory and relapsed vs refractory and intolerant [intolerant to BORT only]), and number of prior therapies (2 vs > 2). The primary endpoint was PFS; secondary endpoints included safety, OS, overall response rate (ORR; ≥ partial response) by IMWG and EBMT criteria, duration of response, time to progression, and quality of life. OS was to be tested only if PFS would be statistically significant; therefore, alpha was controlled at 0.05 2-sided for both PFS and OS. Results: The Data and Safety Monitoring Board (DSMB) reviewed the protocol-specified final analysis results. 455 patients were randomized from March 2011 to Sept 2012. 302 patients received POM + LoDEX, and 153 patients received HiDEX. At the time of analysis, 45% of patients in arm A and 25% of patients in arm B remained on study. The median number of prior therapies was 5 (range, 1–17). 72% of patients were refractory to both LEN and BORT. At the PFS final analysis, with a median follow-up of 18 weeks, PFS was significantly longer with POM + LoDEX vs HiDEX alone (median 15.7 vs 8.0 weeks; 267 total events; hazard ratio [HR], 0.45; P <.001). OS interim analysis was performed as planned; OS also was significantly longer with POM + LoDEX vs HiDEX alone (median not reached vs 34 weeks; 134 events; HR, 0.53; P<.001), crossing the prespecified O’brien-Fleming superiority boundary. This includes 45 pts who received POM after progressing on HiDEX. Median duration of treatment was 12.4 weeks in arm A and 8 weeks in arm B. Following DSMB review of the data, immediate crossover of arm B patients to arm A was recommended. Overall, 25% of patients in arm A and 38% in arm B died, with progressive disease and infections as the primary reasons. Frequent grade 3/4 hematologic toxicities included neutropenia (42% in arm A vs 15% in arm B), thrombocytopenia (21% vs 24%), and febrile neutropenia (7% vs 0%). Other toxicities (grade 3/4) were predominantly infections (24% vs 23%), hemorrhage (3% vs 5%), glucose intolerance (3% vs 7%), neuropathy (1% vs 1%), and venous thromboembolism (1% vs 0%). The primary reason for discontinuation was progressive disease: 35% arm A and 49% arm B. Complete results will be presented at the meeting. Conclusions: POM + LoDEX significantly increased PFS and OS compared with HiDEX in patients who are refractory to LEN and BORT, a population with limited treatment options. The OS superiority boundary was crossed. Based on these data, POM + LoDEX should become the new standard of care in patients who have exhausted the novel agents, LEN and BORT. Disclosures: Dimopoulos: Celgene: Honoraria. Off Label Use: Pomalidomide is an investigational drug and is not approved for the treatment of patients with any condition. Lacy:Celgene: Research Funding. Moreau:Celgene: Honoraria, Speakers Bureau. Weisel:Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Song:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Delforge:Celgene: Consultancy, Honoraria, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria; OrthoBiotech: Consultancy, Honoraria, Speakers Bureau. Karlin:Celgene: Consultancy. Goldschmidt:Novartis: Honoraria, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau. Yu:Celgene: Employment. Sternas:Celgene: Employment, Equity Ownership. Jacques:Celgene: Employment, Equity Ownership. Zaki:Celgene: Employment, Equity Ownership. San Miguel:Onyx: Membership on an entity’s Board of Directors or advisory committees; Janssen: Membership on an entity’s Board of Directors or advisory committees; Millennium: Membership on an entity’s Board of Directors or advisory committees; Celgene: Membership on an entity’s Board of Directors or advisory committees; Novartis: Membership on an entity’s Board of Directors or advisory committees.
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Côté, M., B. D'Antono, M. Sturmer, et al. "552 Patient distress following fidelis defibrillator lead advisory." Canadian Journal of Cardiology 27, no. 5 (2011): S259—S260. http://dx.doi.org/10.1016/j.cjca.2011.07.456.
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MAHONEY, DIANA. "Lead in Artificial Turf Leads to CDC Advisory." Internal Medicine News 41, no. 14 (2008): 8. http://dx.doi.org/10.1016/s1097-8690(08)70750-9.
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Scully, Marie, Spero R. Cataland, Flora Peyvandi, et al. "Results of the Randomized, Double-Blind, Placebo-Controlled, Phase 3 Hercules Study of Caplacizumab in Patients with Acquired Thrombotic Thrombocytopenic Purpura." Blood 130, Suppl_1 (2017): LBA—1—LBA—1. http://dx.doi.org/10.1182/blood.v130.suppl_1.lba-1.lba-1.
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Abstract Introduction: Acquired or immune-mediated thrombotic thrombocytopenic purpura (aTTP) is a life-threatening thrombotic microangiopathy characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia. Inhibitory autoantibodies cause a severe deficiency of the von Willebrand factor (vWF) cleaving enzyme ADAMTS13, leading to intravascular vWF-platelet aggregation and microvascular thrombosis. The mainstays of treatment are plasma exchange (PE) and immunosuppression. Caplacizumab, a bivalent Nanobody, targets the A1 domain of vWF, inhibiting the interaction between ultra-large vWF and platelets. Methods: Patients with an acute episode of aTTP who had received one PE treatment were randomized 1:1 to placebo or 10 mg caplacizumab, in addition to daily PE and corticosteroids. A single IV dose of study drug was given before the first on-study PE and a SC dose was given daily during the PE period and 30 days thereafter. If at the end of this period there was evidence of ongoing disease, such as suppressed ADAMTS13 activity, investigators were encouraged to extend the blinded treatment for a maximum of 4 weeks together with optimization of immunosuppression. All patients entered a 28-day treatment-free follow up period after the last dose of study drug (Figure 1). Primary endpoint was time to platelet count response, defined as platelet count ≥ 150×109/L with stop of daily PE within 5 days. There were 4 key secondary endpoints, hierarchically ranked. The 1st was a composite of aTTP-related death, aTTP recurrence, or major thromboembolic event during the study drug treatment period. A blinded, independent committee adjudicated aTTP-related deaths and major thromboembolic events. The 2nd looked at recurrences during the entire study period, including the follow up period. The 3d evaluated refractoriness to therapy, defined as absence of platelet count doubling after 4 days of treatment and LDH still above normal. The 4th was the time to normalization of 3 organ damage markers: LDH, cardiac troponin I and serum creatinine. Results: 145 patients were randomized, 73 to placebo and 72 to caplacizumab. Demographics and baseline disease characteristics were balanced between groups, except for a higher proportion of initial episodes in the caplacizumab arm. Compared to patients treated with placebo, those on caplacizumab were &gt;50% more likely to achieve a platelet response at any given time point (platelet count normalization rate 1.55, 95% CI 1.10 - 2.20, p &lt;0.01). During the study drug treatment period, treatment with caplacizumab resulted in a 74% reduction in TTP-related death, recurrence of TTP, or a major thromboembolic event (p &lt;0.0001, Table 1). During the overall study period, 28 patients in the placebo group experienced a recurrence versus 9 patients in the caplacizumab group, a 67% reduction (p &lt;0.001, Table 2). In all 6 caplacizumab-treated patients with a relapse during the follow up period, ADAMTS13 activity was still &lt;10% at stop of study drug, reflecting ongoing disease. No caplacizumab-treated patients were refractory to therapy, while 3 patients on placebo were (p =0.057). Treatment with caplacizumab was associated with a trend toward faster normalization of the 3 organ damage markers. Safety is summarized in Table 3. In the caplacizumab group, the most common study drug-related TEAEs were epistaxis, gingival bleeding, and bruising. During the study drug treatment period, 3 patients on placebo died. One death occurred during the follow up period in a caplacizumab-treated patient and was assessed by the investigator as not related to study drug. Conclusions: Results of the Phase 3 HERCULES study confirm that treatment with caplacizumab reduces the time to platelet count response, resulting in faster resolution of aTTP. Treatment with caplacizumab also resulted in a highly clinically meaningful reduction in aTTP-related death, recurrence of aTTP, or a major thromboembolic event during study drug treatment. The relapses after stop of study drug in patients with ADAMTS13 activity &lt;10% suggest that treatment should be continued until complete resolution of the underlying disease. Caplacizumab has a favorable safety profile, with mucocutaneous bleeding the most frequently reported AE. Caplacizumab, through rapid blocking of vWF-mediated platelet aggregation, represents a novel treatment option for patients with aTTP. (clinicaltrials.gov: NCT02553317) Disclosures Scully: Ablynx: Honoraria, Research Funding; Shire: Honoraria, Research Funding; Novartis: Honoraria; Alexion: Honoraria. Cataland:Ablynx NV: Membership on an entity's Board of Directors or advisory committees. Peyvandi:Ablynx, Roche: Membership on an entity's Board of Directors or advisory committees; Ablynx, Bayer, Grifols, Novo Nordisk, Sobi: Speakers Bureau;Freeline, Kedrion, LFB, Octapharma: Consultancy. Coppo:Ablynx: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees. Knöbl:Novo Nordisk: Consultancy, Research Funding; Shire: Consultancy, Research Funding. Kremer Hovinga:Baxalta/Shire: Other: unrestricted grant hereditary TTP registry; Ablynx NV: Membership on an entity's Board of Directors or advisory committees. Metjian:Ablynx NV, Shire, Omeros: Research Funding; Shire: Membership on an entity's Board of Directors or advisory committees. de la Rubia:Amgen: Other: Honoraria; Celgene: Other: Honoraria; Janssen: Other: Honoraria. Pavenski:Alexion Pharmaceuticals: Honoraria; Novartis: Honoraria; Ablynx: Other: participation in industry sponsored RCT; CSL Behring: Research Funding. Callewaert:Ablynx NV: Employment. Biswas:Ablynx NV: Employment. De Winter:Ablynx NV: Employment. Zeldin:Ablynx NV: Employment.
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Nangalia, Jyoti, Charles Massie, E. Joanna Baxter, et al. "The Genomic Landscape of Myeloproliferative Neoplasms: Somatic Calr Mutations in the Majority of JAK2-Wildtype Patients." Blood 122, no. 21 (2013): LBA—2—LBA—2. http://dx.doi.org/10.1182/blood.v122.21.lba-2.lba-2.
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Abstract BCR-ABL negative myeloproliferative neoplasms (MPNs), such as polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) are chronic myeloid malignancies characterized by overproduction of hematopoietic cells. JAK2 mutations are found in most patients with PV, and in only 50-60% of patients with ET and MF. JAK2 mutation testing has greatly simplified MPN diagnosis, but distinguishing JAK2-wildtype ET from reactive thrombocytosis remains a diagnostic challenge. Mutations in signalling pathways (MPL, LNK) and epigenetic regulators (TET2, DNMT3A, IDH1/2, EXH2, ASXL1) have been found in a minority of MPNs. However genome-wide data are lacking and the pathogenesis of MPNs that do not harbor JAK2 or MPLmutations remains obscure. Methods Exome sequencing was performed in 151 MPN patients on matched tumor and constitutional samples. CALR status was assessed in 3412 samples using Sanger sequencing and analysis of exome/genome sequencing data. Presence of CALR mutations in hematopoietic stem and progenitor cells was assessed by flow sorting and sequencing. Phylogenetic trees were established using hematopoietic colonies. Calreticulin cellular localisation was assessed in patient samples and cell lines expressing CALR variants by flow cytometry and immunofluorescence. Results Exome sequencing identified 1498 somatic mutations with a median of 6.5 mutations in PV and ET, and 13 in MF (MF vs ET, P=0.0002; MF vs PV, P=0.008). JAK2V617F was found in all cases of PV (n=48), 56% of ET (35/62), and 69% of MF (27/39), and MPL mutations in 7 ET and MF cases. Mutations in epigenetic regulators TET2, DNMT3A, ASXL1, EZH2, and IDH1/2 were identified in 22, 12, 12, 4, 3 patients respectively, and components of the splicing machinery (U2AF1, SF3B1 or SRSF2) were mutated in 9 patients. Mutations in rare genes reported to be mutated in MPNs were found in four patients (1 CBL; 2 NFE2; 1 SH2B3/LNK). We found novel somatic mutations in CHEK2 (1 PV, 1 ET and 1 MF) which have not been previously reported in MPNs. The mutation spectrum showed a predominance of C>T transitions. Pairwise associations between MPN genes demonstrated that ASXL1 and SRSF2 mutations were positively correlated with mutations in epigenetic modifiers. Novel somatic mutations in calreticulin (CALR) were identified by exome sequencing in the majority (26/31) of JAK2 or MPL unmutated patients. CALR and JAK2/MPL mutations were mutually exclusive, and 97% of patients harbored a mutation in 1 of these 3 genes. In an extended follow up screen of 1345 hematological malignancies, 1517 other cancers and 550 controls we found CALR mutations in 71% of ET (80/112), 56% of idiopathic MF (18/32), 86% of post ET-MF (12/14) and 8% of myelodysplasia (10/115), but not in other myeloid, lymphoid or solid cancers. Compared to JAK2-mutated MPNs, those with CALR mutations presented with higher platelet counts (Wilcoxon rank-sum, P=0.0003), lower hemoglobin levels (Student’s t test, P=0.02) and showed a higher incidence of transformation to MF (Fishers exact, P=0.03). All CALR mutations were insertions or deletions affecting exon 9, with 2 common variants L367fs*46 (52 bp deletion) and K385fs*47 (5 bp insertion). Loss of heterozygosity over CALR was seen in a minority of patients. Of 148 CALR mutations identified, there were 19 distinct variants. Remarkably, all generated a +1 basepair frameshift, which results in loss of most of the C-terminal acidic domain of the protein as well as the KDEL Golgi-to-endoplasmic reticulum (ER) retrieval signal, raising the possibility of compromised ER retention. Mutant proteins were readily detected in transfected cell lines and localised to the ER in the same manner as wildtype CALR, without Golgi or cell surface accumulation. These results are consistent with studies reporting KDEL-independent mechanisms of ER retention. Mutation of CALR was detected in highly purified hematopoietic stem/progenitor cells. Clonal analyses demonstrated CALR mutations in the earliest phylogenetic node in 5/5 patients, consistent with it being an initiating mutation in these individuals. Conclusions We describe the mutational landscape of BCR-ABL negative MPNs and demonstrate that somatic mutations in the endoplasmic reticulum chaperone CALR are found in the majority of patients with JAK2-unmutated MPNs. These results reveal a novel biological pathway as a target for tumorigenic mutations and will simplify diagnosis of MPN patients. Disclosures: Bowen: Celgene: Honoraria. Harrison:S Bio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Shire: Speakers Bureau; Celgene: Honoraria; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Vannucchi:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees.
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König, Thomas, Bernd Luig, and Stephan Marc Solomon. "Sachverständige und der Einfluss von Expertise auf Reformen: Eine räumliche Analyse der Föderalismusreform II." Perspektiven der Wirtschaftspolitik 11, no. 3 (2010): 307–23. http://dx.doi.org/10.1111/j.1468-2516.2010.00337.x.
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AbstractThis article sheds light on the relationship between politicians and scientific advisors in the second stage of reform of Germany’s fiscal federalism. Based on the principal agent theory and a specific model presented by Bueno de Mesquita we derive two hypotheses. Concretely, we expect that policy change depends on both the homogeneity of the experts’ signals (H1) and the strength of the experts’ signals independently of their preferred policies (H2). For an empirical investigation, we exploit a dataset that includes information about the status quo, the experts’ positions and the degree of policy change relating to 416 conflict issues. According to two separate questionnaires in the policy advisory process we differentiate between the fiscal reform in narrower sense and the administrative reform. Our findings show that H1 and H2 have explanatory power for the partly far-reaching fiscal reform, whereas only H1 explains the “fig leaf” of administrative reform.
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Ravandi, Farhad, Ellen Ritchie, Hamid Sayar, et al. "Improved Survival in Patients with First Relapsed or Refractory Acute Myeloid Leukemia (AML) Treated with Vosaroxin Plus Cytarabine Versus Placebo Plus Cytarabine: Results of a Phase 3 Double-Blind Randomized Controlled Multinational Study (VALOR)." Blood 124, no. 21 (2014): LBA—6—LBA—6. http://dx.doi.org/10.1182/blood.v124.21.lba-6.lba-6.
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Abstract Introduction: Despite 40 years of intense clinical research, there remain no new approved treatments or standard of care for patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). New safe and effective salvage treatments are urgently needed. Vosaroxin is a first-in-class anticancer quinolone derivative that is active in AML. Vosaroxin is minimally metabolized, evades P glycoprotein receptormediated efflux and has activity independent of p53 status. VALOR is a rigorously designed and conducted phase 3, adaptive design, randomized, double-blind, placebo-controlled trial evaluating vosaroxin plus cytarabine (vos/cyt) vs placebo plus cytarabine (pla/cyt) in patients with R/R AML (NCT01191801). Methods: Patients were randomized 1:1 to receive cytarabine (1 g/m2 IV over 2 hr, d 1-5) plus either vosaroxin (90 mg/m2 IV over 10 min d 1 and 4; 70 mg/m2 in subsequent cycles) or placebo. Up to 2 induction and 2 consolidation cycles were administered. Eligible patients had refractory disease (persistent disease after induction, or first complete remission [CR1] < 90 d) or were in first relapse (early relapse: CR1 of 90 d to 12 mo; late relapse: CR1 of 12 mo to 24 mo). Patients had received 1-2 cycles of prior induction chemotherapy including at least 1 cycle of anthracycline (or anthracenedione) and cytarabine. Randomization was stratified by disease status (refractory, early relapse, late relapse), age (< 60, ≥ 60 years), and geographic location (US, non-US). Primary efficacy and safety endpoints were overall survival (OS) and 30- and 60-day mortality; secondary endpoints were complete remission (CR) rate and incidence of adverse events (AEs). Results: Between Dec 2010 and Sept 2013, 711 patients were randomized to receive vos/cyt (n = 356) or pla/cyt (n = 355) at 124 sites; per the adaptive design, a prespecified 1-time sample size increase of 225 patients was implemented after the interim analysis. At the final analysis, median OS was 7.5 mo (95% CI: 6.4-8.5) with vos/cyt vs 6.1 mo (95% CI: 5.2-7.1) with pla/cyt (HR = 0.866 [95% CI: 0.73-1.02]; 2-sided unstratified log-rank P = 0.06) (Figure). The OS difference was statistically significant in a preplanned analysis accounting for the stratification factors at randomization (2-sided stratified log-rank P = 0.02). Overall, 29.5% of patients underwent allogeneic stem cell transplant (ASCT), including 45.8% of patients < 60 years and 20.2% of patients ≥ 60 years. Transplant rates were comparable between the 2 treatment arms (30.1% with vos/cyt and 29.0% with pla/cyt). In a predefined analysis censoring for subsequent ASCT, median OS was improved with vos/cyt (6.7 mo vs 5.3 mo with pla/cyt; HR = 0.81 [95% CI: 0.67-0.97]; P = 0.02; stratified P = 0.03) (Figure). In predefined subgroup analyses, OS benefit was greatest in patients aged ≥ 60 years (7.1 mo with vos/cyt vs 5.0 mo with pla/cyt; HR = 0.75; P = 0.003) (Figure) and those with early relapse (6.7 mo vs 5.2 mo; HR = 0.77; P = 0.04). OS with vos/cyt vs pla/cyt was 9.1 mo vs 7.9 mo in patients < 60 years (HR = 1.08; P = 0.60); 6.7 mo vs 5.0 mo in patients with refractory disease (HR = 0.87; P = 0.23); and 14.1 mo vs 12.3 mo in patients with late relapse (HR = 0.98; P = 0.96), respectively. A CR was achieved in 30.1% of patients treated with vos/cyt vs 16.3% treated with pla/cyt (P = 0.00001). Thirty-day and 60-day all-cause mortality was similar in the 2 arms (30-day: 7.9% vs 6.6%; 60-day: 19.7% vs 19.4% with vos/cyt vs pla/cyt, respectively). Most common serious AEs were febrile neutropenia (11.3% with vos/cyt vs 7.4% with pla/cyt), sepsis (8.7% vs 4.3%), pneumonia (7.6% vs 4.9%), bacteremia (8.5% vs 2.9%), and stomatitis (3.4% vs 1.4%). Serious and non-serious cardiac, renal, neurologic, and hepatic AEs were comparable between treatment groups. Conclusion: Vos/cyt demonstrated improved OS and higher CR rates in patients with R/R AML without increased early mortality. In the primary OS analysis, the overall clinical benefit associated with vosaroxin may be underestimated, particularly in younger patients, due to the confounding effect of high transplant rates, a methodological limitation of AML trials. Vosaroxin-containing therapy had acceptable tolerability. VALOR results represent one of the largest datasets available in this setting, and the OS benefit was confirmed by a robust sensitivity analysis. These data support the use of this combination as a new option for salvage therapy in patients with R/R AML. Figure 1 Figure 1. Disclosures Ravandi: Sunesis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Sayar:Sunesis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Strickland:Sunesis: Membership on an entity's Board of Directors or advisory committees. Schiller:Sunesis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Erba:Sunesis: Consultancy; Seattle Genetics: Consultancy; Novartis: Consultancy; Incyte: Consultancy; Celgene: Consultancy; Amgen: Consultancy. Pigneux:Sunesis: Consultancy. Horst:Sunesis: Research Funding. Recher:Sunesis: Consultancy; Celgene: Consultancy, Research Funding; Chugai: Research Funding. Klimek:Sunesis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Craig:Sunesis: Equity Ownership. Fox:Sunesis: Consultancy, Equity Ownership. Ward:Sunesis: Employment, Equity Ownership. Smith:Sunesis: Employment, Equity Ownership. Acton:Sunesis: Consultancy. Mehta:Sunesis: Consultancy. Stuart:Sunesis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Saglio, Giuseppe, Dong-Wook Kim, Surapol Issaragrisil, et al. "Nilotinib Demonstrates Superior Efficacy Compared with Imatinib in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase: Results From the International Randomized Phase III ENESTnd Trial." Blood 114, no. 22 (2009): LBA—1—LBA—1. http://dx.doi.org/10.1182/blood.v114.22.lba-1.lba-1.
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Abstract Abstract LBA-1 Background: Nilotinib is a highly potent and the most selective inhibitor of BCR-ABL, the only proven molecular target for CML therapy. ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients) is a phase 3, randomized, open-label, multicenter study comparing the efficacy and safety of 300 or 400 mg bid nilotinib with 400 mg qd imatinib in patients (pts) with newly diagnosed Ph+ CML in chronic phase (CML-CP). Methods: 846 pts with newly diagnosed Ph+ CML-CP, diagnosed within 6 mos, and stratified by Sokal risk score, were randomized 1:1:1 to nilotinib 300 mg bid (n=282), nilotinib 400 mg bid (n=281), and imatinib 400 mg qd (n=283) arms. The primary endpoint was rate of major molecular response (MMR) at 12 months (mos). All pts had a minimum of 12 mos of treatment or discontinued early; median follow-up was 14 mos. MMR was defined as a value of ≤ 0.1% of BCR-ABL/ABL ratio on the International Scale. Molecular response was assessed by RQ-PCR at baseline, monthly for 3 mos and every 3 mos thereafter. Samples were analyzed at a central PCR laboratory. The major secondary endpoint was rate of complete cytogenetic response (CCyR) by 12 mos based on bone marrow cytogenetics. Results: Baseline demographics, disease characteristics, and Sokal scores were well balanced among the 3 arms; pts with high-risk Sokal scores were 28% in all arms. Median dose intensities of nilotinib delivered were 592 mg/day for 300 mg bid and 779 mg/day for 400 mg bid; imatinib dose intensity was 400 mg/day. Overall, 84%, 82%, and 79% of pts remained on the study for 300 mg bid nilotinib, 400 mg bid nilotinib, and 400 mg qd imatinib, respectively. Rates of MMR at 12 mos (Table) were superior for nilotinib 300 mg bid compared with imatinib 400 mg qd (44% vs. 22%,P < .0001) and also for nilotinib 400 mg bid compared with imatinib 400 mg qd (43% vs. 22%,P < .0001). Median time to MMR among pts who achieved MMR was faster for nilotinib 300 mg bid (5.7 mos) and nilotinib 400 mg bid (5.8 mos) compared with imatinib 400 mg qd (8.3 mos). Rates of CCyR by 12 mos were significantly higher for both nilotinib at either 300 mg bid compared with imatinib 400 mg qd (80% vs. 65%,P < .0001) and for nilotinib 400 mg bid compared with imatinib 400 mg qd (78% vs. 65%,P = .0005). Overall, progression to advanced disease was lower for nilotinib 300 mg bid (2 pts) and nilotinib 400 mg bid (1 pt) compared with imatinib 400 mg qd (11 pts). Overall, both drugs were well-tolerated. Rates of discontinuation due to adverse events or laboratory abnormalities were 7% for nilotinib 300 mg bid, 11% for nilotinib 400 mg bid, and 9% for imatinib 400 mg qd. Pts were monitored for QT prolongation and LVEF. No patients in any treatment arm showed a QTcF interval > 500 msec. There was no decrease from baseline in mean LVEF anytime during treatment in any arm. The study is ongoing. Conclusions: Nilotinib at both 300 mg bid and 400 mg bid induced significantly higher and faster rates of MMR and CCyR compared with imatinib 400 mg qd, the current standard of care in pts with newly diagnosed CML. Nilotinib was effective across all Sokal scores. After only one year of treatment, both nilotinib arms resulted in a meaningful clinical benefit compared to imatinib, with reduction of transformation to AP/BC. Nilotinib exhibited a favorable safety and tolerability profile. The superior efficacy and favorable tolerability profile of nilotinib compared with imatinib suggests that nilotinib may become the standard of care in newly diagnosed CML. Disclosures: Saglio: Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Off Label Use: Nilotinib is not currently approved for first-line treatment of CML. The presentation will report the results from a randomized study of imatinib versus nilotinib in patients with newly diagnosed Ph+ CML-CP. Kim:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Wyeth: Research Funding. le Coutre:Novartis: Honoraria, Research Funding; BMS: Honoraria. Reiffers:Novartis: Research Funding. Pasquini:Novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; BMS: Membership on an entity’s Board of Directors or advisory committees; Schering: Membership on an entity’s Board of Directors or advisory committees. Clark:Novartis: Honoraria, Research Funding, Speakers Bureau. Hughes:Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Hochhaus:Novartis: Research Funding. Gallagher:Novartis: Employment, Equity Ownership. Hoenekopp:Novartis: Employment. Dong:Novartis: Employment, Equity Ownership. Haque:Novartis: Employment. Larson:Novartis:
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Duncan, Leah. "The Proxy Problem: Using Nonprofits to Solve Misaligned Incentives in the Proxy Voting Process." Michigan Business & Entrepreneurial Law Review, no. 9.2 (2020): 235. http://dx.doi.org/10.36639/mbelr.9.2.proxy.
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Proxy advisory firms and their influence on the proxy voting process have recently become the subject of great attention for the Securities and Exchange Commission (“SEC”) among other constituencies. A glance at recent proxy season recaps and reports, many of which devote space to discussing proxy advisory firm recommendations, reveal the significance of this influence on institutional voting. As Sagiv Edelman puts it, “proxy advisory firms exist at the nexus of some of the most high-profile corporate law discussions—most notably, the shareholder voting process, which has recently been the subject of much scholarly and legal debate.” The SEC has responded by announcing that it intends to reform the regulations, or lack thereof, surrounding proxy advisory firms. Recently, the SEC issued proposed amendments to Exchange Act Rule 14(a)-1 which would effectively codify their earlier interpretation of solicitation under this rule. The proposed amendment would “condition the availability of certain existing exemptions from the information and filing requirements . . . for proxy voting advice businesses upon compliance with additional disclosures and procedural requirements.” Furthermore, the amendments would clarify when a lack of disclosure of certain information in proxy voting advice compromises the accuracy of the advice and misleads within the meaning of the rule. The SEC believes that these extra requirements will “help ensure that investors who use proxy voting advice receive more accurate, transparent, and complete information on which to make their voting decisions.” Based on this proposal, it is apparent that the SEC is intent on rectifying some of the problems of transparency and conflicts of interest associated with proxy advisory firms. Given the increasing influence of proxy advisory firms, the misalignment of incentives between proxy firms and the institutional shareholders who use proxy firm services is troubling. This Note identifies inherent problems and concerns with proxy advisory firms and offers solutions to these issues with a focus on eliminating conflicts of interest. Using Henry Hansmann’s theory of ownership, this Note argues that nonprofit ownership of proxy advisory firms eliminates both information asymmetry and conflicts of interest inherent to the current ownership structure. Part I provides a brief overview of the problems and concerns associated with proxy advisory firms. Part II suggests two potential solutions: that Rule 206(4)-6 of the Investment Adviser Act of 1940 should be repealed or alternatively, that nonprofit ownership through investment company associations is a more effective way for investment management companies to comply with their fiduciary duties. Because profit incentive has created conflicts of interest that lead to proxy advice that may not always be in the best interest of investment manager clients, nonprofit ownership promotes transparency that allows parties who rely on the advice to make more independent decisions. Part III argues that nonprofit ownership is the most viable alternative to the status quo.
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Davies, E. "Former Bush adviser is appointed to lead Global Fund." BMJ 345, no. 16 3 (2012): e7820-e7820. http://dx.doi.org/10.1136/bmj.e7820.
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Damicone, J. P., K. E. Jackson, J. R. Sholar, and M. S. Gregory. "Evaluation of a Weather-Based Spray Advisory for Management of Early Leaf Spot of Peanut in Oklahoma1." Peanut Science 21, no. 2 (1994): 115–21. http://dx.doi.org/10.3146/i0095-3679-21-2-10.
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Abstract A simplified version of the weather-based advisory program developed by Parvin, Smith, and Crosby (PSC) for scheduling fungicide sprays for management of early leaf spot (Cercospora arachidicola Hori) of peanut (Arachis hypogea L.) was evaluated under various productions systems in Oklahoma from 1990-1992. Over eight trials with spanish cultivars, the number of sprays per season averaged 5.7 for the 14-d schedule and 4.0 for the advisory program. Final disease incidence (symptomatic and defoliated leaflets) with the fungicide chlorothalonil (1.26 kg/ha) averaged 15% for the 14-d schedule, 34% for the advisory program, and 77% for the control. However, disease incidence (75%) and defoliation (50%) approached unacceptable levels on the spanish cultivars in some trials. In six trials with runner cultivars, the number of sprays averaged 6.7 for the 14-d schedule and 4.7 for the advisory program. Final disease incidence with chlorothalonil on the runner cultivars averaged 5% for the 14-d schedule, 14% for the advisory program, and 68% in the control. Yields did not differ in any of the 14 trials between the advisory and 14-d programs using chlorothalonil. Yields averaged 3015, 3003, and 2303 kg/ha for spanish cultivars and 4108, 3855, and 3066 kg/ha for runner cultivars with the 14-d schedule, advisory program, and control, respectively. The advisory program was effective in irrigated trials where weather stations were deployed either under or outside the influence of irrigation. The fungicides tebuconazole at 0.14 kg/ha and propiconazole at 0.13 kg/ha generally provided better leaf spot control with the advisory program than chlorothalonil. The post-infection activity of these fungicides was observed in one trial and probably accounts for their improved performance. Yields were reduced and leaf spot incidence was high where tank mixes of benomyl (0.28 kg/ha) or thiophanatemethyl (0.38 kg/ha) plus mancozeb (1.68 kg/ha) were used with the advisory program. Area under the disease progress curve, leaf spot incidence, and defoliation in the controls were lower for runner than for spanish cultivars at sites where both market types were planted in adjacent trials. Fungicides applied according to the advisory program provided better leaf spot control on the runner cultivars. Results showed the need for a weather-based advisory which allows greater levels of leaf spot control on spanish cultivars than the PSC advisory.
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Warner, Mark. "Sir Sam Edwards. 1 February 1928 — 7 July 2015." Biographical Memoirs of Fellows of the Royal Society 63 (January 2017): 243–71. http://dx.doi.org/10.1098/rsbm.2016.0028.
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Sam Edwards was one of the leading physicists of the second half of the twentieth century. He was Cavendish Professor at the University of Cambridge, a Vice President of the Royal Society, a member of the Académie des Sciences and of the US National Academy, and a senior figure in the university and his college. He played a major role in public life, most notably as chairman of the Science Research Council (SRC), responsible for research funding in the UK. He was chairman of the British Association, chief government scientist to the Department of Energy, and chairman of the Defence Scientific Advisory Council. He was equally in demand to lead or to help set up bodies abroad, particularly the Max Planck Institute for Polymers in Mainz, Germany. Remarkably, Sam made some of his most celebrated scientific discoveries, for instance the theory of spin glasses and the rheology of high polymer melts, while serving as the full-time head of the SRC. Conversely, his scientific insights informed his leadership in advising the government. His later science was in highly applicable areas: he was an active advisor to Unilever, Dow, Lucas and many other companies that rely on research.
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Sekeres, Mikkael A., Megan Othus, Alan F. List, et al. "A Randomized Phase II Study of Azacitidine Combined with Lenalidomide or with Vorinostat Vs. Azacitidine Monotherapy in Higher-Risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML): North American Intergroup Study SWOG S1117." Blood 124, no. 21 (2014): LBA—5—LBA—5. http://dx.doi.org/10.1182/blood.v124.21.lba-5.lba-5.
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Abstract Background: Higher-risk MDS and CMML comprise a spectrum of disorders associated with cytopenias, high risk of transformation to acute myeloid leukemia (AML), and truncated survival. Initial treatment with a hypomethylating agent such as azacitidine (AZA) is considered standard of care. Whether addition of the histone deacetylase inhibitor vorinostat (VOR), which acts synergistically with AZA to reactivate epigenetically silenced genes, or addition of lenalidomide (LEN), which impacts the bone marrow microenvironment, improves response rates compared to AZA monotherapy is unknown. Methods: This Phase II study (ClinTrials.gov # NCT01522976) randomized higher-risk MDS (International Prognostic Scoring System (IPSS) Int-2 or High and/or bone marrow blasts >5%) and CMML patients (pts) with <20% blasts to receive AZA (75 mg/m2/d on d1-7 of a 28d cycle), AZA + LEN (10 mg/d on d1-21), or AZA + VOR (300 mg BID on d3-9). Eligibility criteria included: >18 years (yrs), no previous allogeneic transplant, no prior treatment with any of the study drugs, and adequate organ function; therapy-related (t)MDS was allowed. Pts continued treatment until disease progression, relapse, unacceptable toxicity, or lack of response. Dose reductions occurred for unresolved grade >3 adverse events (per NCI CTCAE) or delayed count recovery. The primary endpoint was improvement in overall response rate (ORR), by intention to treat and reviewed centrally, of one of the combination arms vs. AZA monotherapy per 2006 International Working Group MDS response criteria (complete response (CR) + partial response (PR) + hematologic improvement (HI)). Relapse-free survival (RFS) was from time of response. The study had 81% power to detect a 20% improvement in ORR from 35% to 55%. Results: Of 282 pts enrolled from 3/12–6/14, 276 are included in analyses (6 ineligible pts excluded): 92 on the AZA arm, 93 on AZA+LEN, and 91 on AZA+VOR. Baseline characteristics were well-balanced across arms (Table). Pts received a median of 23 weeks of therapy: 25 of AZA; 24 of AZA+LEN; and 20 of AZA+VOR and were followed for a median of 9 months (range: 0-26). Numbers of pts with notable adverse events >grade 3 for AZA:AZA+LEN:AZA+VOR included febrile neutropenia (10:13:13); gastrointestinal disorders (4:11:23); infections (2:3:3); and rash (2:12:1). Responses were assessable in 260 pts (94%). ORR for the entire cohort was 33%: 19% CR, 1% PR, and 13% HI, with a median RFS of 7 months. ORR was similar across study arms: 36% for AZA, 37% for AZA+LEN (p=1.0 vs. AZA), and 22% for AZA+VOR (p=.07 vs. AZA). CR/PR/HI rates across arms were also similar: 23%/0%/13% for AZA; 18%/1%/17% for AZA+LEN (CR p=.47 vs. AZA); and 14%/1%/7% for AZA+VOR (CR p=.18 vs. AZA); rates of bone marrow exams to assess response were 76%, 67%, and 73%, respectively. HI-P/HI-E/HI-N rates were 21%/15%/5% for AZA, 26%/14%/15% for AZA+LEN, and 12%/8%/4% for AZA+VOR. HI-N rates were higher in AZA+LEN vs. AZA (p=.05) but otherwise were similar across arms. Median time to best response across arms was 15 weeks in AZA, 16 weeks in AZA+LEN, and 16 weeks in AZA+VOR. ORR did not vary significantly across arms in subgroup analyses for tMDS, baseline red blood cell (RBC) transfusion dependence, and by IPSS risk group. ORR for CMML pts for AZA:AZA+LEN:AZA+VOR was 33%:53%(p=.15 vs. AZA):12%(p=.41 vs. AZA). Allogeneic transplantation rates were: 7 pts on AZA, 6 on AZA+LEN, and 9 on AZA+VOR. For AZA:AZA+LEN:AZA+VOR, median RFS was: 6:8:11 months (log-rank p=.3 for combination arms vs. AZA, Figure); and for pts on therapy >6 months, it was 7:7.5:13 months (log-rank p=.11 for AZA+VOR, .74 for AZA+LEN vs. AZA). Conclusions: In higher-risk MDS pts, ORR was similar for AZA monotherapy compared to AZA-containing combination arms, though some subgroups may have benefitted from combination therapy. Differences in types of response may have resulted from differential rates of follow-up bone marrow assessments. While a non-significant signal of a DFS advantage for combination therapy was observed, longer-term outcome data are being assessed. Table Table. Figure Figure. Disclosures Sekeres: Boehringer-Ingelheim: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Off Label Use: lenalidomide, vorinostat for higher-risk MDS. List:Celgene Corporation: Consultancy. Gore:Celgene: Consultancy, Research Funding. Attar:Celgene: Consultancy. Erba:Seattle Genetics: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Research Funding; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda Pharmaceuticals International Co.: Research Funding; Astellas Pharma: Research Funding; Celgene: Honoraria, Speakers Bureau.
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Jacoby, Meagan A., Laura E. Finn, Ashkan Emadi, et al. "Post-Marketing Observational Study to Assess the Incidence of Infusion-Related Reactions in Adult Patients with Therapy-Related Acute Myeloid Leukemia (AML) or AML with Myelodysplasia-Related Changes Who Were Treated with CPX-351." Blood 136, Supplement 1 (2020): 19. http://dx.doi.org/10.1182/blood-2020-136880.
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Introduction: CPX-351 (Vyxeos®; daunorubicin and cytarabine liposome for injection), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, has been approved by the US FDA and EMA for the treatment of adults with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes. The primary endpoint analysis of the pivotal phase 3 study (NCT01696084) that formed the basis for the approvals evaluated older patients with newly diagnosed high-risk/secondary AML; after a median follow-up of 20.7 months, CPX-351 significantly improved median overall survival (OS) versus conventional 7+3 (9.56 vs 5.95 months; HR = 0.69 [95% CI: 0.52, 0.90]; 1-sidedP= 0.003), with a comparable safety profile and 2 infusion-related reaction events. After 5 years of follow-up, the improved median OS was maintained, with a HR (0.70) consistent with the primary endpoint analysis. Infusion-related reactions are generally common with liposomal drugs; this post-marketing observational study was therefore requested by the FDA to confirm observations from the phase 3 study by assessing the incidence and severity of infusion-related reactions during induction with CPX-351 in adults with AML. Methods: This was an observational, single-arm study (NCT03526926); prior to enrollment, the decision to prescribe CPX-351 was made based on the approved US indications and dosing. Patients who had been previously treated with CPX-351 or any investigational agent were ineligible. Eligible patients aged ≥18 years were to receive induction with CPX-351 at the label dosage of 100 units/m2 (cytarabine 100 mg/m2 and daunorubicin 44 mg/m2) by 90-minute IV infusion on Days 1, 3, and 5; the observation period included only the first 6 days of the first induction cycle, although patients may have received subsequent treatment cycles at their physician's discretion. The incidence and severity of infusion-related reactions were evaluated during and for 90 minutes after the completion of each infusion. Treatment-emergent adverse events (TEAEs) were collected from the start of the first infusion until 1 day after the last infusion of the first induction cycle (Day 6) and graded according to CTCAE v4.03. TEAEs were followed until resolution, stabilization, or permanent sequelae were identified, or the patient was lost to follow-up. Results: In total, 52 patients were enrolled in the study. The median age was 64 years (range: 28, 78), with 67% of patients aged ≥60 years; 56% were male; and 23%, 46%, and 23% of patients had an ECOG performance status of 0, 1, and 2, respectively. A majority of patients had no history of allergies (64%), allergic asthma (98%), or autoimmune disorders (87%). Most patients (94%) received all 3 CPX-351 infusions, with a mean of 2.9 infusions per patient (standard deviation: 0.3). Patients received a median cumulative daunorubicin dose of 247.5 mg (range: 88, 339) and cytarabine dose of 562.5 mg (range: 204, 774). One (2%) patient experienced infusion-related reactions during the study. The patient experienced grade 1 pyrexia on Day 2 (25 hours after the Day 1 infusion) and grade 2 dyspnea on Day 4 (21 hours after the Day 3 infusion). The infusion-related reactions did not lead to dose change, interruption, or discontinuation of treatment. In total, 39 (75%) patients experienced any-grade TEAEs, and 13 (25%) patients experienced grade 3 or 4 TEAEs within the 6-day study period. Serious TEAEs were reported by 6 (12%) patients and included respiratory failure (n = 2 [4%]), pyrexia, lung infection, sepsis, tumor lysis syndrome, cerebrovascular accident, embolism, and dyspnea (n = 1 [2%] each); serious TEAEs resolved after treatment in 2 patients. Three deaths reported during the study were due to serious TEAEs considered unrelated to CPX-351 (sepsis, thromboembolic event, and stroke; n = 1 [2%] each). Conclusions: In this post-marketing observational study in patients with AML, the frequency of infusion-related reactions was low (1 of 52 patients) and the reactions were grade 1-2 in severity. Although this study only collected data on adverse events during and immediately after infusion of the first induction cycle of CPX-351, the TEAEs and serious TEAEs reported were consistent with those seen in AML patients receiving induction chemotherapy. These data support the prior safety profile reported in the pivotal phase 3 study, with no new safety signals identified. Disclosures Jacoby: Jazz Pharmaceuticals:Research Funding;AbbVie:Research Funding.Finn:Jazz Pharmaceuticals:Speakers Bureau;Celgene:Speakers Bureau;Seattle Genetics:Speakers Bureau.Emadi:Jazz Pharmaceuticals:Research Funding;NewLink Genetics:Research Funding;Amgen:Membership on an entity's Board of Directors or advisory committees;KinaRx:Other: co-founder and scientific advisor;Genentech:Membership on an entity's Board of Directors or advisory committees;Servier:Membership on an entity's Board of Directors or advisory committees.Saba:Kyowa Kirin:Other: Advisory Board;Janssen:Other: Advisory Board, Speakers Bureau;AbbVie:Consultancy, Other: Advisory Board, Speakers Bureau;Pharmacyclics:Other: Advisory Board, Speakers Bureau;Kite:Other: Advisory Board.Powell:Pfizer:Research Funding;Novartis:Research Funding;Jazz Pharmaceuticals:Consultancy, Other: Advisor, Research Funding;Rafael Pharmaceuticals:Consultancy, Other: Advisor, Research Funding;Genentech:Research Funding.Seiter:Alexion:Speakers Bureau;AbbVie:Speakers Bureau;Onconova:Research Funding;Forma:Research Funding;Jazz Pharmaceuticals:Honoraria, Research Funding, Speakers Bureau;Sanofi:Honoraria, Speakers Bureau;Incyte:Honoraria, Speakers Bureau;Celgene:Honoraria, Research Funding, Speakers Bureau;Novartis:Honoraria, Research Funding, Speakers Bureau;Sun Pharma:Research Funding;Roche:Research Funding;Amphivena:Research Funding.Garcia:Jazz Pharmaceuticals:Current Employment, Current equity holder in publicly-traded company.Faderl:Jazz Pharmaceuticals:Current Employment, Current equity holder in publicly-traded company.
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Kuehn, Bridget M. "Panel Advises Tougher Limits on Lead Exposure." JAMA 307, no. 5 (2012): 445. http://dx.doi.org/10.1001/jama.2012.50.
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De Maio, Carmela, and Anibeth Desierto. "First year Business students’ perceptions of academic support through embedding. A Practice Report." Student Success 7, no. 1 (2016): 57–63. http://dx.doi.org/10.5204/ssj.v7i1.324.
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This paper explores the perceptions of first year Business students to embedding sessions and additional support workshops offered through a collaboration between learning advisors and lecturers in a first year foundational unit. Through a social constructivist lens and utilising action research methods, questionnaires (n=42) were administered to two cohorts of students at the conclusion of the unit in 2011 and 2012 to explore firstly, whether or not they perceived the embedding sessions to be of benefit and, secondly, whether having the learning advisor in the class made them more likely to utilise additional support outside class time. In addition, the researchers sought to explore whether there were any improvements in students’ final results which might be attributable to the academic support offered to them through the embedding sessions. The findings from the quantitative and qualitative data suggest that the students perceived the embedding workshops as having positive effects on their academic literacy skills. Furthermore, there was a slight increase in the number of students that sought additional support outside of class time. However, it appears that the embedding workshops did not lead to an improvement in students’ final marks for the unit and this is an area which requires further investigation.
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Vranová, Vilma. "Options of self-treatment in increased fatigue: What a pharmacist can advise." Praktické lékárenství 14, no. 3 (2018): 135–39. http://dx.doi.org/10.36290/lek.2018.027.
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Jacobi, J. C. "AU-Pnuts Advisory II: Modification of the Rule-Based Leaf Spot Advisory System for a Partially Resistant Peanut Cultivar." Plant Disease 79, no. 7 (1995): 672. http://dx.doi.org/10.1094/pd-79-0672.
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Willison, Donald J., Joslyn Trowbridge, Michelle Greiver, Karim Keshavjee, Doug Mumford, and Frank Sullivan. "Participatory governance over research in an academic research network: the case of Diabetes Action Canada." BMJ Open 9, no. 4 (2019): e026828. http://dx.doi.org/10.1136/bmjopen-2018-026828.
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Digital data generated in the course of clinical care are increasingly being leveraged for a wide range of secondary purposes. Researchers need to develop governance policies that can assure the public that their information is being used responsibly. Our aim was to develop a generalisable model for governance of research emanating from health data repositories that will invoke the trust of the patients and the healthcare professionals whose data are being accessed for health research. We developed our governance principles and processes through literature review and iterative consultation with key actors in the research network including: a data governance working group, the lead investigators and patient advisors. We then recruited persons to participate in the governing and advisory bodies. Our governance process is informed by eight principles: (1) transparency; (2) accountability; (3) follow rule of law; (4) integrity; (5) participation and inclusiveness; (6) impartiality and independence; (7) effectiveness, efficiency and responsiveness and (8) reflexivity and continuous quality improvement. We describe the rationale for these principles, as well as their connections to the subsequent policies and procedures we developed. We then describe the function of the Research Governing Committee, the majority of whom are either persons living with diabetes or physicians whose data are being used, and the patient and data provider advisory groups with whom they consult and communicate. In conclusion, we have developed a values-based information governance framework and process for Diabetes Action Canada that adds value over-and-above existing scientific and ethics review processes by adding a strong patient perspective and contextual integrity. This model is adaptable to other secure data repositories.
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De Rosa, Michele, and Tomas Rydberg. "SETAC LCA advisory groups silver jubilee: get involved and contribute to the next stage of LCA." International Journal of Life Cycle Assessment 22, no. 2 (2016): 293–95. http://dx.doi.org/10.1007/s11367-016-1192-8.
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Krahn, Andrew D., Jean Champagne, Jeffrey S. Healey, et al. "Outcome of the Fidelis implantable cardioverter-defibrillator lead advisory: A report from the Canadian Heart Rhythm Society Device Advisory Committee." Heart Rhythm 5, no. 5 (2008): 639–42. http://dx.doi.org/10.1016/j.hrthm.2008.01.029.
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