Summary Background Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs. We aimed to assess the efficacy and safety of the microsomal triglyceride transfer ...protein inhibitor lomitapide in adults with this disease. Methods We did a single-arm, open-label, phase 3 study of lomitapide for treatment of patients with homozygous familial hypercholesterolemia. Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26. Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day. The primary endpoint was mean percent change in levels of LDL cholesterol from baseline to week 26, after which patients remained on lomitapide through to week 78 for safety assessment. Percent change from baseline to week 26 was assessed with a mixed linear model. Findings 29 men and women with homozygous familial hypercholesterolaemia, aged 18 years or older, were recruited from 11 centres in four countries (USA, Canada, South Africa, and Italy). 23 of 29 enrolled patients completed both the efficacy phase (26 weeks) and the full study (78 weeks). The median dose of lomitapide was 40 mg a day. LDL cholesterol was reduced by 50% (95% CI −62 to −39) from baseline (mean 8·7 mmol/L SD 2·9) to week 26 (4·3 mmol/L 2·5; p<0·0001). Levels of LDL cholesterol were lower than 2·6 mmol/L in eight patients at 26 weeks. Concentrations of LDL cholesterol remained reduced by 44% (95% CI −57 to −31; p<0·0001) at week 56 and 38% (–52 to −24; p<0·0001) at week 78. Gastrointestinal symptoms were the most common adverse event. Four patients had aminotransaminase levels of more than five times the upper limit of normal, which resolved after dose reduction or temporary interruption of lomitapide. No patient permanently discontinued treatment because of liver abnormalities. Interpretation Our study suggests that treatment with lomitapide could be a valuable drug in the management of homozygous familial hypercholesterolaemia. Funding FDA Office of the Orphan Product Development, Aegerion Pharmaceuticals.
156 Art as a Multiplier of Science Communication Skarke, Carsten; German, Jessica; Meagher, Emma A.
Journal of clinical and translational science,
04/2024, Letnik:
8, Številka:
s1
Journal Article
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OBJECTIVES/GOALS: Scientists are increasingly confronted with 'science critical' #_msocom_1 belief systems. The politicization of science fuels hesitancy towards evidence-based therapies. To overcome ...these barriers, we aim to devise strategies to communicate clinical translational science (CTS) through art. METHODS/STUDY POPULATION: A two-year pilot artist-in-residency (AIR) program embedded in the Translational Research Immersion Program (TRIP). Since 2009, TRIP contributes to CTS Workforce Development (WD) through a 10-week mentored, curriculum-rich summer undergraduate research experience. Students are recruited from 5 regional institutions, 6 HBCUs, and the University of Puerto Rico. AIR is composed of 3 phases: the “Immersive Phase” where the artist gains intensive exposure to the scientific process through the lived experience of TRIP students, the “Productive Phase” where the artist conceptualizes the process of CTS into works of art, and the “Engagement Phase” where the CTS workforce, artists, and community members coalesce around science-to-art materializations. RESULTS/ANTICIPATED RESULTS: In 2022 & 2023 the AIR participated in ~35hrs of CTS research seminars, panel discussions, and professional skills workshops. Additional TRIP student-AIR interaction occurred in focus groups including visits to mentor’s labs. An AIR-led workshop culminated in an Empowering CTS Communication event where TRIP students engaged with community members through elevator pitches of their CTS summer project on a speed-rotating basis. A month-long art-CTS exhibition planned for 3/2024 will feature contributions from AIR, TRIP students, and ITMAT community members. Qualitative insights were that TRIP is an effective art-science incubator, students strengthened their CTS communication skills, art functions as an icebreaker between science and communities with an ocean of opportunities for science education. DISCUSSION/SIGNIFICANCE: AIR embedded into existing CTS WD programs is proposed as creative approach to strengthen the reputation of science in the public. CTS-informed art functions as connective tissue between public and CTS workforce. The hands-on experience to adopt art as a science communication tool is a powerful soft skill for the next generation of CTS investigators.
As the nation seeks to recruit and retain physician-scientists, gaps remain in understanding and addressing mitigatable challenges to the success of faculty from underrepresented minority (URM) ...backgrounds. The Doris Duke Charitable Foundation Fund to Retain Clinical Scientists program, implemented in 2015 at 10 academic medical centers in the United States, seeks to retain physician-scientists at risk of leaving science because of periods of extraordinary family caregiving needs, hardships that URM faculty-especially those who identify as female-are more likely to experience. At the annual Fund to Retain Clinical Scientists program directors conference in 2018, program directors-21% of whom identify as URM individuals and 13% as male-addressed issues that affect URM physician-scientists in particular. Key issues that threaten the retention of URM physician-scientists were identified through focused literature reviews; institutional environmental scans; and structured small- and large-group discussions with program directors, staff, and participants. These issues include bias and discrimination, personal wealth differential, the minority tax (i.e., service burdens placed on URM faculty who represent URM perspectives on committees and at conferences), lack of mentorship training, intersectionality and isolation, concerns about confirming stereotypes, and institutional-level factors. The authors present recommendations for how to create an environment in which URM physician-scientists can expect equitable opportunities to thrive, as institutions demonstrate proactive allyship and remove structural barriers to success. Recommendations include providing universal training to reduce interpersonal bias and discrimination, addressing the consequences of the personal wealth gap through financial counseling and benefits, measuring the service faculty members provide to the institution as advocates for URM faculty issues and compensating them appropriately, supporting URM faculty who wish to engage in national leadership programs, and sustaining institutional policies that address structural and interpersonal barriers to inclusive excellence.
In addition to restrictions on conducting research, COVID-19-related travel bans and scientific meeting cancellations have negatively affected scholars in the Clinical and Translational Science Award ...(CTSA) Mentored Career Development Award (KL2) program. In response, a national virtual visiting scholar program was developed to provide opportunity for KL2 scholars to be virtual visiting professors at another CTSA hub, meet faculty and scholars, and expand networks and build collaborations. This article describes the design and short-term outcomes of the virtual CTSA Visiting Scholar Program. In 2020, a working group designed core program elements and developed an application and selection process. Anonymized surveys were sent to scholars post visit and to scholars and program directors 6 months post visit to evaluate their experience and solicit suggestions for improvements. Between November 2020 and May 2021, 56 KL2 scholars and 27 hubs participated. Forty-five (80.4%) participating scholars responded to the initial survey. Nearly all scholars (44, 97.7%) agreed their experience was valuable. All respondents indicated they would recommend the program to other KL2 scholars. For the 6-month survey, the response rate was 87.5% (49/56). Within 6 months of their visit, 36 (73.5%) respondents had contacted at least one person at the host hub and for 17 (34.7%) respondents, new collaborations with the host hub ensued. Twenty-five of 27 (92.6%) host hubs responded to the survey. Most (21, 84.0%) agreed that hearing visiting scholar talks was valuable to their own scholars and 23 (92%) indicated likelihood of their hub participating in future round of the program. The virtual Visiting Scholar Program provided KL2 scholars an opportunity to virtually visit another CTSA hub, present their research, and meet with faculty and other scholars to expand their networks. Although geared to KL2 scholars, this model is potentially generalizable to other nationally coordinated career development programs.
Since the inception of the Clinical and Translational Science Award (CTSA) program in 2006, leaders in education across CTSA sites have been developing and updating core competencies for Clinical and ...Translational Science (CTS) trainees. By 2009, 14 competency domains, including biomedical informatics, had been identified and published. Since that time, the evolution of the CTSA program, changes in the practice of CTS, the rapid adoption of electronic health records (EHRs), the growth of biomedical informatics, the explosion of big data, and the realization that some of the competencies had proven to be difficult to apply in practice have made it clear that the competencies should be updated. This paper describes the process undertaken and puts forth a new set of competencies that has been recently endorsed by the Clinical Research Informatics Workgroup of AMIA. In addition to providing context and background for the current version of the competencies, we hope this will serve as a model for revision of competencies over time.
Effective mentorship is recognized as critical for the professional development of clinical and translational investigators. Evidence-based mentorship training prompted the development of training ...for mentees at early career stages who are navigating both mentor and mentee roles. The curriculum titled,
for Early Career Investigators, recognizes the importance of building mentee self-efficacy across proactive mentorship skills and competencies.
curriculum is based on the research mentor training approach in Entering Mentoring. Pilot implementations of
at the University of Wisconsin-Madison and University of Pennsylvania had positive training outcomes for KL2 Scholars. Subsequently, Mentoring Up was implemented and evaluated at several other institutions. For 26 implementations longer than 4 hours, data were collected on trainee demographics, satisfaction with training, skill gains across mentorship competencies, and the intent to change mentoring behaviors following training.
88% of participants rated the mentee training as valuable. Significant skill gains were reported across all mentorship competencies following training. 77% reported specific plans to change or augment their mentoring behaviors because of the training. The majority aligned with mentorship skill competencies (
) or mentoring up strategies (
).
training is effective in advancing mentee skills and promoting strategies to be more proactive in getting their mentoring needs met.
offers an expansion to the suite of mentorship education and resources to support the career advancement of all in the translational science workforce.
The COVID-19 pandemic had an immediate impact on the lives and work of early-career researchers. We leveraged a cluster-randomized trial and compared survey data collected over two timepoints to ...explore whether these impacts persisted. Although more than a year had passed, 74% of participants reported that their research was affected in multiple ways in
2020 and 2021. These data suggest that the effects of the pandemic on early-career researchers may be prolonged. Our findings additionally serve as an impetus to identify and implement solutions to early-career challenges that undoubtedly existed before the pandemic, but which COVID-19 brought into the spotlight.
The invited authors of these papers provide an overview of the principles of pedagogy, best practices to frame educational initiatives and goals to achieve competency, and best practices for ...approaching specific types of learners and learning environments. Following an internal review process, the group selected five evidenced-based reviews and special communications that describe best practices for: (1) the use of gamification in CTS education; (2) the use of storytelling to communicate CTS to a broad audience of learners; (3) the use of online learning/instructional technology techniques to advance learning; (4) addressing and diversifying the CTS pipeline; and (5) education focused on dissemination and implementation science. ...we would like to thank all the authors who rose to the challenge of contributing to this issue and thank the editorial staff of JCTS for their assistance.
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