External Advisory Board Research Articles

A Protocol for the Inclusion of Minoritized Persons in Alzheimer Disease Research From the ADNI3 Diversity Taskforce

Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults. To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3. This cross-sectional study used baseline data from a longitudinal, multisite, observational study conducted from January 15, 2021, to July 12, 2022, with no follow-up. The study was conducted at 13 ADNI3 sites in the US. Participants included individuals aged 55 to 90 years without cognitive impairment and those with mild cognitive impairment or Alzheimer disease. Efforts included (1) launch of an external advisory board, (2) changes to the study protocol, (3) updates to the digital prescreener, (4) selection and deployment of 13 community-engaged research study sites, (5) development and deployment of local and centralized outreach efforts, and (6) development of a community-science partnership board. Screening and enrollment numbers from centralized and local outreach efforts, digital advertisement metrics, and digital prescreener completion. A total of 91 participants enrolled in the trial via centralized and local outreach efforts, of which 22 (24.2%) identified as Latinx and 55 (60.4%) identified as Black (median [IQR] age, 65.6 [IQR, 61.5-72.5] years; 62 women [68.1%]). This represented a 267.6% increase in the monthly rate of enrollment (before: 1.11 per month; during: 4.08 per month) of underrepresented populations. For the centralized effort, social media advertisements were run between June 1, 2021, and July 31, 2022, which resulted in 2079 completed digital prescreeners, of which 1289 met criteria for subsequent site-level screening. Local efforts were run between June 1, 2021, to July 31, 2022. A total of 151 participants underwent site-level screening (100 from local efforts, 41 from centralized efforts, 10 from other sources). In this cross-sectional study of pilot inclusion efforts, a culturally informed, community-engaged approach increased the inclusion of Black and Latinx participants in an Alzheimer disease cohort study.

The Africa non-communicable diseases (NCD) Open Lab: Impact of a portfolio of clinical studies to deepen the understanding of NCDs in sub-Saharan Africa.

Clinical research in sub-Saharan Africa (SSA) has often focussed on communicable diseases. However, with the increasing burden of non-communicable diseases (NCDs), there is a need for Africa-specific NCD research. GSK established the Africa NCD Open Lab in 2014. Three calls for proposals were advertised through various media channels. An external independent scientific advisory board, predominantly representing African scientists and NCD experts, reviewed and selected projects to receive funding. An additional programme in the Africa NCD Open Lab was designed to build statistical capability by supporting training initiatives. We assessed the impact of the Africa NCD Open Lab in three ways: scientific quality with impact; research training and professional development; and research environments. We captured metrics through regular reports/interactions with researchers; via a final report; and through exit interviews with principal investigators. Twenty projects in 11 African countries were funded; reports from 18 completed projects are available (data capture is ongoing). Overall, 139 articles have been published in peer-reviewed journals and other data have been presented at conferences and other forums. Most completed projects led to positive outcomes, such as further research, informing policy, or positively impacting clinical care, including three projects that saw changes to regional or national practice guidelines: the CREOLE study in Nigeria; the African Severe Asthma Program in Uganda; and the African Prospective Study on the Early Detection and Identification of Cardiovascular Disease and Hypertension in South Africa. Participation in the Africa NCD Open Lab led to the award of 34 grants related to or influenced by increased research capacity or experience. Significant professional development related to the projects also occurred with higher-level degrees being awarded, including 30 MScs, 30 PhDs, and nine postdoctoral fellowships. Through these projects, research capacity was strengthened across the region by equipping core research facilities, training research staff, strengthening research support services, and supporting the expansion of investigator networks. The completed Africa NCD Open Lab projects demonstrate high-quality research outcomes addressing important health challenges with potential benefits to African populations. Based on the success of the Africa NCD Open Lab, additional funding has been secured to extend the Open Lab initiative.

FC29: Development of an Informant-Reported Lucidity Measure

Objective:The aim was to develop a lucidity measure for use with front-line caregivers to describe lucidity episodes among individuals with dementia, neurological and other illnesses and identify associated individual and episodic event characteristics.Methods:Qualitative: An external advisory board reviewed the clarity, breadth, and scope of the conceptual definition and item content. Modified focus groups were conducted with 20 staff and 10 family members who participated using a web-based survey. Data were extracted from Qualtrics for analysis using NVivo. Semi-structured cognitive interviews were conducted with10 health professionals working with older adults with cognitive impairment.Quantitative: A combined exploratory and confirmatory factor analysis was performed to test for dimensionality. The explained common variance (ECV), calculated as the percent of observed variance was estimated. Estimates of internal consistency such as ordinal alpha and McDonald’s omega were computed in R and Mplus.Results:Data were collected from 50 staff informants on behalf of 302 residents, 25 with lucidity events. The majority (74%) of those interviewed were certified nursing assistants. Most (58%) of the sample of residents were White and 21% Black or African American. One fourth (25%) were Hispanic or Latino. Most (80% to 90%) of those with lucidity events were reported to have memory deficits and at least 70% required maximal assistance in performing basic tasks such as dressing. Most events (60%) were of short duration (10 minutes or less), and included showing facial expressions (83%) and making eye contact (88%). One half spoke multiple sentences. About half were reported to hold a conversation, and speak coherently to convey needs; 40% were able to remember and mention the name of relatives. Staff reactions were of surprise (60%) shock (52%) and happiness (50%).Data for item modification derived from the focus groups and cognitive interviews resulted in the final lucidity measure. Internal consistency estimates were high, with most ranging from 0.76 to 0.98. The ECVs were high for most scales, indicative of essential unidimensionality.Discussion:The dimensionality and reliability analyses results were strong, and supportive of unidimensional scales with high internal consistency. The feasibility of conducting assessments of lucidity events was established.

PEREGRINATIONS ON THE STUDY OF THE OPTICAL PROPERTIES OF NONSPHERICAL PARTICLES

PEREGRINATIONS ON THE STUDY OF THE OPTICAL PROPERTIES OF NONSPHERICAL PARTICLES

Unexpected lucidity in dementia: application of qualitative methods to develop an informant-reported lucidity measure

Objectives Unexpected lucidity is a phenomenon of scientific, clinical, and psychological relevance to health professionals, to those who experience it, and their relatives. This paper describes qualitative methods used to develop an informant-based measure of lucidity episodes. Methods The approach was refinement of the operationalization of the construct; review of seminal items, modification, and purification; and confirmation of the feasibility of reporting methodology. Modified focus groups were conducted with 20 staff and 10 family members using a web-based survey. Themes included reaction when hearing the term; words that come to mind; description of and first reaction to referenced or observed ‘lucidity’ events. Semi-structured cognitive interviews were conducted with 10 health professionals working with older adults with cognitive impairment. Data were extracted from Qualtrics or Microsoft 365 Word® for analysis using NVivo. Results Conceptual issues, as well as issues regarding comprehension, interpretation, clarity, semantics, and standardization of definitions derived from an external advisory board, focus groups and cognitive interviews informed items’ modification, and resulted in the final lucidity measure. Conclusions An obstacle to understanding the mechanisms and estimating the prevalence of lucid events among individuals with dementia and other neurological conditions is the scarcity of reliable and valid measures. The substantive and varied data gathered from multiple methods including the collaborative work of an External Advisory Board, modified focus groups with staff and family caregivers, and structured cognitive interviews with health professionals were central in creating the revised version of the lucidity measure.

Editorial introductions.

Current Opinion in Nephrology and Hypertension was launched in 1992. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of nephrology and hypertension is divided into 12 sections that are each reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Nancy J. BrownNancy J. BrownNancy J. Brown, MD is the Jean and David W. Wallace Dean of Yale School of Medicine, USA, and the C.N.H. Long Professor of Internal Medicine. Prior to assuming the role of dean at Yale in 2020, Dr Brown served for nine years as the Chair of the Department of Medicine at Vanderbilt University Medical Centre, Tennessee, USA, where she established herself as a national leader in the development of infrastructure to promote the career success of physician-scientists. She founded the Vanderbilt Master of Science in Clinical Investigation program in 2000, served as Associate Dean for Clinical and Translational Scientist Development at Vanderbilt from 2006 to 2010, and as Director of the Division of Clinical Pharmacology from 2009 to 2010. Dr Brown's NIH-funded research focuses on cardiovascular pharmacology and vascular biology in humans. She is particularly interested in understanding the mechanisms of anti-hypertensive and anti-diabetic drugs that are peptidase inhibitors, including the angiotensin-converting enzyme inhibitors, dipeptidyl peptidase 4 inhibitors, and neprilysin inhibitors. Her group has elucidated not only how these drugs decrease inflammation, enhance fibrinolysis (the breakdown of blood clots), and improve glucose homeostasis, but also how they interact with one another and sometimes cause side effects. This understanding leads to optimizing outcomes in patients with hypertension and diabetes. Dr Brown received her A. B. in Molecular Biophysics and Biochemistry from Yale and her MD from Harvard Medical School, USA. She completed her clinical training and a fellowship in clinical pharmacology at Vanderbilt University, Tennessee, USA. Dr Brown is a Fellow of the American Association for the Advancement of Science and a member of the American Society of Clinical Investigation, the Association of American Physicians, the National Academy of Medicine, and the American Academy of Arts and Sciences. She is a Master of the American College of Physicians and a fellow of the Royal College of Physicians. She has served on the National Advisory Research Resources Council and the National Heart, Lung, and Blood Advisory Council of the National Institutes of Health. Dr Brown currently serves on the visiting committee for Harvard Medical School and the External Advisory Board for the Harvard-MIT Health Sciences and Technology program. She is a member of the Scientific Advisory Board of Alnylam Pharmaceuticals. David S. GoldfarbDavid S. GoldfarbDavid S. Goldfarb, MD is Professor of Medicine and Physiology at New York University Grossman School of Medicine, USA. He is the Clinical Chief of the Nephrology Division at New York University Langone Health, and Chief of the Nephrology Section and Director of the Hemodialysis Unit at the New York VA Medical Center in Manhattan, USA. He serves as the Director of the Kidney Stone Prevention Programs at NYU Langone and at New York VA Medical Center, USA. He graduated from Yale College and the Yale School of Medicine, USA, and trained in Internal Medicine at New York VA and New York University, USA, and Nephrology at New York University, USA. He teaches first year renal physiology and renal pathophysiology at NYU, where he has been Teacher of the Year on 3 occasions. Dr Goldfarb is an internationally renowned expert in kidney stone prevention. He is a principal investigator of the Rare Kidney Stone Consortium. Dr Goldfarb is the former President of the NY Society of Nephrology and of the ROCK Society (Research on Calculus Kinetics). He was vice-chair of the American Urological Association's guideline panel, representing the American Society of Nephrology, on Medical Management of Kidney Stones. He is a co-inventor of Moonstone, the first high citrate beverage. He was selected as “Stone Crusher of the Year” in 2014 by the Oxalosis and Hyperoxaluria Foundation and “Nephrologist of the Year” in 2016 by the American Kidney Fund. He has had three calcium oxalate stones.

APPLICATION OF QUALITATIVE METHODS IN THE DEVELOPMENT OF AN INFORMANT-REPORTED MEASURE OF LUCIDITY

Abstract The aim was a qualitative evaluation of a lucidity measure for front-line staff or family informants. A sequential approach to item development and evaluation was followed: refinement of the operationalization of the construct; review of seminal items, modification, and purification; confirmation of the feasibility of reporting methodology. Modified focus groups were conducted with 20 staff and 10 family members who participated using a web-based survey. Sample themes included: reaction when hearing the term; words that come to mind; description of and first reaction to referenced or observed “lucidity” events. Data were extracted from Qualtrics for analysis using NVivo. Semi-structured cognitive interviews were conducted with10 health professionals working with older adults with cognitive impairment. An external advisory board reviewed the clarity, breadth, and scope of the conceptual definition and item content. Suggestions for item modification derived from the focus groups and cognitive interviews resulted in the final lucidity measure.

Abstract 1189: OncoKB, MSK’s precision oncology knowledge base

Abstract OncoKB, Memorial Sloan Kettering Cancer Center’s (MSK) precision oncology knowledge base (www.oncokb.org), is a comprehensive database that annotates the oncogenic effects and clinical actionability of somatic alterations in cancer. OncoKB supports variant interpretation by the cBioPortal for Cancer Genomics and is used to annotate >12,000 MSK patient sequencing reports annually. Since its introduction in 2016, OncoKB has expanded to include 5685 alterations in 682 genes, and in October 2021, it became the first somatic knowledge base to be partially recognized by the FDA. The scope of the OncoKB FDA recognition includes clinically actionable variants that map to an FDA level of evidence, the processes of variant curation, and policies regarding database oversight, personnel training and transparency of data sources and operations. This recognition credentials OncoKB as providing accurate, reliable and clinically meaningful information to the medical and scientific communities. The OncoKB Therapeutic (Tx) Levels of Evidence categorize variants based on their tumor type-specific predictive value of sensitivity or resistance to matched standard care or investigational targeted therapies. To date, OncoKB includes 43 Level 1 genes (included in the FDA drug label), 23 Level 2 genes (included in professional guidelines), 25 Level 3A genes (predictive of drug response in well-powered clinical studies), 23 Level 4 genes (predictive of drug response based on compelling biological evidence), and 11 R1 or R2 resistance genes. Initially focused on solid tumors, OncoKB was expanded to include hematologic disease annotation in 2019 and introduced Diagnostic (Dx) and Prognostic (Px) levels of evidence. All three level of evidence systems (Tx, Dx and Px) are consistent with the guidelines for evidence-based categorization of somatic variants published as a joint consensus recommendation by AMP/ASCO/CAP. OncoKB is governed by a Clinical Genomics Annotation Committee, composed of MSK physicians and scientists who ensure that the information captured is accurate and current, and an external advisory board composed of leaders in the clinical oncology and genomics communities who oversee OncoKB updates and progress. OncoKB curation rules and processes are transparent and documented in the OncoKB Curation Standard Operating Procedure, which is publicly available via the website. User feedback to OncoKB content is encouraged via the website and through cBioPortal. Queries or suggestions by OncoKB users are addressed by the OncoKB team within 72 hours. OncoKB offers licenses for academic, commercial and hospital use, with which users can programmatically access the web API. Future work includes coverage of additional cancer-associated genes, annotation of germline alterations that are predictive of drug response and/or associated with increased heritable cancer risk and the development of a clinical trial matching system. Citation Format: Sarah P. Suehnholz, Moriah Nissan, Hongxin Zhang, Ritika Kundra, Calvin Lu, Benjamin Xu, Maria E. Arcila, Marc Ladanyi, Michael F. Berger, Ahmet Zehir, Aijaz Syed, Julia E. Rudolph, Ross L. Levine, Ahmet Dogan, Jianjiong Gao, David B. Solit, Nikolaus Schultz, Debyani Chakravarty. OncoKB, MSK’s precision oncology knowledge base [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1189.

Development of a competence ecosystem for the future space workforce: strategies, practices and recommendations from international master programs in northern Sweden

Requirements from the global labor market have substantially changed in recent years. Graduate and post-graduate students with excellent subject knowledge, deep understanding of modern working methods, technical and higher-order thinking, engineering intuition and problem-solving skills are in great demand. They should also have professional skills such as well-developed abilities in communication and teamwork, usually in an international work environment. This review discusses the advantages of multidisciplinary study environment, educational strategies such as student-oriented teaching, project-based learning with its applicability to a “real-world” setting, active learning techniques, development of entrepreneurial skills, lessons learned and best practices from the international Master Program in Spacecraft Design and the Joint Master Program in Space Science and Technology – SpaceMaster at Luleå University of Technology in northern Sweden. The importance of complementarity between formal, informal and non-formal learning methods for science and engineering students has been specifically highlighted. Connections to the world of work, through active industry involvement in the education in a systematic way, e.g. External Advisory Board, shared services and facilities, joint projects and supervision of Master and PhD students, is recognised as a key success factor for professional training. A structural combination of modern pedagogical tools, strategic partnership with industry, business entities, academic partners and up-to-date multidisciplinary labs creates the conceptual framework for a Competence Ecosystem for fostering a new generation of space scientists and engineers.

Insights into ovarian response with a fixed low dose FSH stimulation in an IUI programme: the PRORAILS study.

Are patients' characteristics, such as anti-Müllerian hormone (AMH) and BMI, reliable factors to predict ovarian response in couples with unexplained subfertility undergoing IUI with ovarian hyperstimulation (IUI-OH)? We observed no solid relationship between serum AMH and ovarian response. Ovarian stimulation during IUI treatment could lead to a higher chance of pregnancy, but also a higher incidence of multiple pregnancies, unless strict cancellation criteria are being used. Several factors could influence the result of the stimulation, such as age, BMI and hormonal status of the female. In IVF treatment, AMH has shown to be a useful predictor of ovarian stimulation to optimize the outcome; however, in a milder stimulation protocol, such as IUI, this has not been investigated. We performed a prospective cohort study and evaluated the first IUI stimulation cycle of 492 patients. The study was conducted between 2012 and 2017. Follow-up ended if patients were not pregnant after the first cycle. If pregnancy did occur, follow-up lasted until delivery. PRORAILS is a large multicentre nationwide cohort study executed in the Netherlands. Eligible women aged 18-43 years who were diagnosed with unexplained subfertility or mild male subfertility according to the Dutch guideline, with a regular indication for IUI-OH, were asked to participate. Ovarian response was assessed using a transvaginal ultrasound 5-7 days after initiation of the stimulation and was repeated according to the size of the leading follicles. Ovarian response was defined as optimal or suboptimal based on the total number of dominant follicles >15 mm. A successful stimulation was defined as the presence of two to three follicles >15 mm on the day of hCG administration. Serum AMH (µg/l) was measured by ELISA, and samples were taken on day 2, 3 or 4 of the menstrual cycle. Poisson regression was used to estimate the risk of a suboptimal ovarian response. Of the 492 participants, the mean age was 33 years and the mean subfertility duration was 2.5 years. The median serum AMH was 2.1 (µg/l). The majority of patients had a suboptimal response: 326 women (66%), of whom 224 (45%) had a hypo response (defined as <two follicles sized > 15 mm) and 102 (21%) had a hyper response (defined as more than three follicles sized >15 mm). The lowest AMH category showed a trend towards a smaller risk of a suboptimal response (relative risk ratio 0.76 (95% CI 0.54, 1.06)), but this effect did not reach statistical significance. In the prediction models, BMI and serum basal FSH were significant predictors of a hypo response, while for hyper response the factors age, BMI and serum FSH were significant. A higher BMI showed a higher risk for hypo response, as did a higher FSH whereas a lower BMI and lower FSH showed a higher risk for hyper response. The addition of AMH to the models did not improve the predictive abilities. Although the study was prospective, the main analyses were cross-sectional with characteristics measured at one time-point. The study was not powered to provide insight into predictors of pregnancy and live births and, therefore, the result for pregnancy should be interpreted with caution. This was the first large multicentre study that investigated the characteristics of ovarian response categories using standardized methods and centrally analysed laboratory measures. PRORAILS is a nationwide study with 15 hospitals and, therefore, these results are generalizable to other hospitals in the Netherlands. This study provides high-quality outcomes advancing the subfertility research field. Future studies would benefit from a randomized design investigating the effectiveness of an individualized approach versus a fixed dose. Also, the relation between a good ovarian stimulation and pregnancy rate could be further investigated. The PRORAILS study is sponsored by Merck B.V., Schiphol-Rijk, the Netherlands, an affiliation of Merck KGaA, Darmstadt, Germany (EMR700623_612). Merck KGaA, Darmstadt, Germany, reviewed the manuscript prior to submission. The opinions remain those of the authors. Merck KGaA, Darmstadt, Germany, had no influence on the use of medication in this study. The recombinant FSH was mostly provided by Merck B.V. or MSD. F.B. is a member of the external advisory board for Merck B.V., Schiphol-Rijk, the Netherlands, and has received a research grant from Merck B.V., Schiphol-Rijk. H.v.B. is an employee from IQVIA, which is a commercial data-analysing company, and received payment for her part in the article. NCT01662180.

Addendum.

Swartz EE, Register-Mihalik JK, Broglio SP, et al. National Athletic Trainers' Association Position Statement: Reducing Intentional Head-First Contact Behavior in American Football Players. J Athl Train. 2022;57(2):113–124. doi: https://doi.org/10.4085/1062-6050-0062.21Please see the authors' disclosures below.Erik E. Swartz, PhD, ATC, has received grants from the GOG Hawaii Foundation and the Nine Sigma Head Health Challenge and trademark registration for HUTT. Johna K. Register-Mihalik, PhD, LAT, ATC, has received grants from the National Operating Committee on Standards for Athletic Equipment, Department of Defense (DOD), Centers for Disease Control and Prevention (CDC), National Center for Injury Prevention and Control, National Athletic Trainers' Association (NATA) Foundation, National Football League (NFL), and National Collegiate Athletic Association (NCAA)–DOD Mind Matters Research Challenge Award; she is a member of USA Football's Football Development Council. Steven P. Broglio, PhD, ATC, has received funding from the National Institutes of Health, CDC, DOD-USA Medical Research Acquisition Activity, NCAA, NATA Foundation, NFL, Under Armour/GE, Simbex, and ElmindA. He has consulted for the NCAA (travel expenses only), US Soccer, US Cycling (unpaid), and medicolegal litigation and received speaker honoraria and travel reimbursements for talks given. He is on the University of Calgary SHRed Concussions external advisory board (unpaid). Jason P. Mihalik, PhD, CAT(C), ATC, has received grants from the National Institutes of Health, NFL, CDC, and DOD. Kevin M. Guskiewicz, PhD, ATC, has received grants from the NFL (subaward from Boston Children's Hospital) and NCAA and nonfinancial support from the NCAA Scientific Committee. Julian Bailes, MD, is Chairman of the Medical Advisory Committee for Pop Warner Football. Jay L. Myers, PhD, reported no disclosures. Merrill Hoge, BA, has received royalties from Mascot Books for a football-related publication.

Insights from the evaluations of the NIH Centers for Accelerated Innovation and Research Evaluation and Commercialization Hubs programs.

The National Institutes of Health launched the NIH Centers for Accelerated Innovation and the Research Evaluation and Commercialization Hubs programs to develop approaches and strategies to promote academic entrepreneurship and translate research discoveries into products and tools to help patients. The two programs collectively funded 11 sites at individual research institutions or consortia of institutions around the United States. Sites provided funding, project management, and coaching to funded investigators and commercialization education programs open to their research communities. We implemented an evaluation program that included longitudinal tracking of funded technology development projects and commercialization outcomes; interviews with site teams, funded investigators, and relevant institutional and innovation ecosystem stakeholders and analysis and review of administrative data. As of May 2021, interim results for 366 funded projects show that technologies have received nearly $1.7 billion in follow-on funding to-date. There were 88 start-ups formed, a 40% Small Business Innovation Research/Small Business Technology Transfer application success rate, and 17 licenses with small and large businesses. Twelve technologies are currently in clinical testing and three are on the market. Best practices used by the sites included leadership teams using milestone-based project management, external advisory boards that evaluated funding applications for commercial merit as well as scientific, sustained engagement with the academic community about commercialization in an effort to shift attitudes about commercialization, application processes synced with education programs, and the provision of project managers with private-sector product development expertise to coach funded investigators.

Is home-based monitoring of ovulation to time frozen embryo transfer a cost-effective alternative for hospital-based monitoring of ovulation? Study protocol of the multicentre, non-inferiority Antarctica-2 randomised controlled trial.

STUDY QUESTIONThe objective of this trial is to compare the effectiveness and costs of true natural cycle (true NC-) frozen embryo transfer (FET) using urinary LH tests to modified NC-FET using repeated ultrasound monitoring and ovulation trigger to time FET in the NC. Secondary outcomes are the cancellation rates of FET (ovulation before hCG or no dominant follicle, no ovulation by LH urine test, poor embryo survival), pregnancy outcomes (miscarriage rate, clinical pregnancy rates, multiple ongoing pregnancy rates, live birth rates, costs) and neonatal outcomes (including gestational age, birthweight and sex, congenital abnormalities or diseases of babies born).WHAT IS KNOWN ALREADYFET is at the heart of modern IVF. To allow implantation of the thawed embryo, the endometrium must be prepared either by exogenous oestrogen and progesterone supplementation (artificial cycle (AC)-FET) or by using the NC to produce endogenous oestradiol before and progesterone after ovulation to time the transfer of the thawed embryo (NC-FET). During an NC-FET, women visit the hospital repeatedly and receive an ovulation trigger to time FET (i.e. modified (m)NC-FET or hospital-based monitoring). From the woman’s point of view, a more natural approach using home-based monitoring of the ovulation with LH urine tests to allow a natural ovulation to time FET may be desired (true NC-FET or home-based monitoring).STUDY DESIGN, SIZE, DURATIONThis is a multicentre, non-inferiority prospective randomised controlled trial design. Consenting women will undergo one FET cycle using either true NC-FET or mNC-FET based on randomisation.PARTICIPANTS/MATERIALS, SETTING, METHODSBased on our sample size calculation, the study group will consist of 1464 women between 18 and 45 years old who are scheduled for FET. Women with anovulatory cycles, women who need ovulation induction and women with a contra indication for pregnancy will be excluded. The primary outcome is ongoing pregnancy. Secondary outcomes are cancellation rates of FET, pregnancy outcomes (including miscarriage rate, clinical pregnancy, multiple pregnancy rate and live birth rate). Costs will be estimated by counting resource use and calculating unit prices.STUDY FUNDING/COMPETING INTEREST(S)The study received a grant from the Dutch Organisation for Health Research and Development (ZonMw 843002807; www.zonmw.nl). ZonMw has no role in the design of the study, collection, analysis, and interpretation of data or writing of the manuscript. F.B. reports personal fees from member of the external advisory board for Merck Serono, grants from Research support grant Merck Serono, outside the submitted work. A.E.P.C. reports and Unrestricted grant of Ferring B.V. to the Center for Reproductive medicine, no personal fee. Author up-to-date on Hyperthecosis. Congress meetings 2019 with Ferring B.V. and Theramex B.V. M.G. reports Department research and educational grants from Guerbet, Merck and Ferring (location VUMC) outside the submitted work. E.R.G. reports personal fees from Titus Health Care, outside the submitted work. C.B.L. reports grants from Ferring, grants from Merck, from Guerbet, outside the submitted work. The other authors have none to declare.TRIAL REGISTRATION NUMBERDutch Trial Register (Trial NL6414 (NTR6590), https://www.trialregister.nl/).TRIAL REGISTRATION DATE23 July 2017DATE OF FIRST PATIENT’S ENROLMENT10 April 2018

Patient and public involvement in the design and conduct of a large, pragmatic observational trial to investigate recurrent, high-risk non-muscle-invasive bladder cancer.

Patient-centered approaches to research design are particularly important for diseases with complex treatment decision-making, such as recurrent, high-grade non-muscle-invasive bladder cancer (NMIBC). The objective of this article is to describe patient and public involvement (PPI) in designing a large, pragmatic observational trial and to articulate barriers, challenges, and lessons learned for future design. Through multistakeholder involvement, a large, pragmatic observational trial was designed to investigate the outcomes of high-risk, recurrent NMIBC, and it was titled Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer (CISTO). CISTO's design used the Guidance for Reporting Involvement of Patients and the Public 2 reporting checklist for PPI and built on prior engagement infrastructure in partnership with the Bladder Cancer Advocacy Network. CISTO's PPI began with research prioritization to identify the highest priority questions facing patients with NMIBC. A pragmatic observational study design was selected and refined through stakeholder input. PPI included patients and caregivers organized into an advocate advisory board and clinicians, researchers, payers, and industry representatives organized into an external advisory board. An engagement plan was created to define the stages of PPI and the level and nature of the involvement of each group. PPI was measured quantitatively and qualitatively through evaluation surveys and iterative feedback from board members, with changes made for continuous improvement. Through intentional PPI, CISTO aims to produce pragmatic and generalizable results that will allow patients to make informed decisions for recurrent, high-risk NMIBC based on their personal experiences. Involving patients and other stakeholders in research ensures that it reflects the outcomes that matter most to them. This is especially important when research focuses on conditions in which patients face difficult decisions about treatment options. This article describes the key role that stakeholders played in shaping the Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer (CISTO) study. It compares treatments for recurrent noninvasive bladder cancer and describes how stakeholders were engaged to design and develop the study and the practices that supported their involvement.

Lifestyle intervention prior to IVF does not improve embryo utilization rate and cumulative live birth rate in women with obesity: a nested cohort study.

Lifestyle intervention prior to IVF does not improve embryo utilization rate and cumulative live birth rate in women with obesity: a nested cohort study.

Development of a Mobile App for Ecological Momentary Assessment of Circadian Data: Design Considerations and Usability Testing.

BackgroundCollecting data on daily habits across a population of individuals is challenging. Mobile-based circadian ecological momentary assessment (cEMA) is a powerful frame for observing the impact of daily living on long-term health.ObjectiveIn this paper, we (1) describe the design, testing, and rationale for specifications of a mobile-based cEMA app to collect timing of eating and sleeping data and (2) compare cEMA and survey data collected as part of a 6-month observational cohort study. The ultimate goal of this paper is to summarize our experience and lessons learned with the Daily24 mobile app and to highlight the pros and cons of this data collection modality.MethodsDesign specifications for the Daily24 app were drafted by the study team based on the research questions and target audience for the cohort study. The associated backend was optimized to provide real-time data to the study team for participant monitoring and engagement. An external 8-member advisory board was consulted throughout the development process, and additional test users recruited as part of a qualitative study provided feedback through in-depth interviews.ResultsAfter ≥4 days of at-home use, 37 qualitative study participants provided feedback on the app. The app generally received positive feedback from test users for being fast and easy to use. Test users identified several bugs and areas where modifications were necessary to in-app text and instructions and also provided feedback on the engagement strategy. Data collected through the mobile app captured more variability in eating windows than data collected through a one-time survey, though at a significant cost.ConclusionsResearchers should consider the potential uses of a mobile app beyond the initial data collection when deciding whether the time and monetary expenditure are advisable for their situation and goals.

Mediating Effects of Neural Targets on Depression, Weight and Anxiety Outcomes of an Integrated Collaborative Care Intervention: The ENGAGE-2 Mechanistic Pilot RCT

Background: Integrated treatments for depression (and associated anxiety) and obesity are lacking; mechanisms are poorly investigated. This mechanistic pilot trial tested the degree to which engaging pre-specified neural targets at 2 months produces desired outcomes at 6 months. Methods: Adults with a body mass index (BMI) of ≥30 (≥27, if Asian) and Patient Health Questionnaire-9 (PHQ-9) score of ≥10 were recruited from academic internal medicine clinics between March 1, 2019 and March 19, 2020, and followed for 6 months until August 31, 2020. Participants were randomized to receive usual care (n=35) or an integrated collaborative care intervention (n=71), providing 6 problem-solving therapy (PST) sessions for depression by 2 months, 3 additional PST sessions and 11 home videos on lifestyle changes for weight loss by 6 months. Outcomes were changes in BMI, Depression Symptom Checklist 20-item (SCL-20) scores, and Generalized Anxiety Disorder Scale (GAD-7) scores at 6 months. Neural targets were changes in affective, cognitive control, and default mode circuits by functional neuroimaging at 2 months. Outcomes: Among 106 participants (mean [SD] age 47.0 [11.9] years, 76% women, 55% Blacks, 20% Latino, BMI 37.1 [6.0], SCL-20 1.2 [0.7], GAD-7 6.9 [4.8]), 86.8% completed the trial. The intervention led to significant reductions in SCL-20 (-0.3 [95% CI: -0.6, -0.1]) and GAD-7 (-2.9 [-4.7, -1.1]), but not BMI, at 6 months compared with usual care. Changes in the activation or functional connectivity of neural targets in the negative affect (anterior insula, subgenual and pregenual ACC, amygdala) and cognitive control circuits (dlPFC, dACC) at 2 months significantly correlated with changes in GAD-7, but not SCL-20 or BMI, at 6 months, and the correlations differed by the intervention vs. usual care. Effect sizes were medium to large (0.41ꟷ1.18 SDs). Changes in the neural targets of the cognitive control circuit, but not the negative affect circuit, at 2 months differed by treatment group. Effect sizes were medium (0.58ꟷ0.79 SDs). Interpretation: Short-term changes in the cognitive control circuit mediated changes in anxiety symptoms, suggesting possible neural mechanisms to target for enhanced treatment effect. Clinical Trial Registration Details: ClinicalTrials.gov Identifier: NCT03841682. Funding Information: National Heart, Lung, and Blood Institute grant number UH2HL132368 and UH3HL132368. Declaration of Interests: Dr. Jun Ma is a paid scientific consultant for Health Mentor, Inc. (San Jose, CA). Dr. Leanne M. Williams is on the Scientific Advisory Board for One Mind Psyberguide and the External Advisory Board for the Laureate Institute for Brain Research. Dr. Olusola A. Ajilore is the co-founder of Keywise AI and serves on the advisory boards of Blueprint Health and Embodied Labs. The other authors report no conflicts of interest. Dr. Thomas Kannampallil is a paid consultant for Pfizer, Inc, outside of this work Ethics Approval Statement: The Institutional Review Boards for the University of Illinois at Chicago and Stanford University approved the study. All participants provided written consent.

First Person Profile: Cheryl Willman, MD: As director and CEO of the University of New Mexico Comprehensive Cancer Center, Dr. Willman has led major health equity initiatives while making pioneering discoveries in precision medicine.

First Person Profile: Cheryl Willman, MD: As director and CEO of the University of New Mexico Comprehensive Cancer Center, Dr. Willman has led major health equity initiatives while making pioneering discoveries in precision medicine.

30718 Evaluating and advancing the CTSA external advisory board: Best practices

ABSTRACT IMPACT: The goal of this evaluation study is to enhance the ability of the External Review Board to advise the CTSA at UTMB how to improve translational science activities. OBJECTIVES/GOALS: The purpose of this study is to evaluate the work of the External Review Board (EAB) for the Institute for Translational Sciences/CTSA at the University of Texas Medical Branch-Galveston. This evaluation is conducted through the perceptions of professional and community board members. The outcome consists of an inventory of best practices. METHODS/STUDY POPULATION: We collected data by means of semi-structured interviews with all eight member of the EAB. The interviews were conducted via telephone, lasted approximately 30 minutes each, and were audio-recorded with respondents’ permission. Respondents’ identities were held in confidence. The IRB at UTMB reviewed our study. The interviews were transcribed. The data were analyzed by means of an inductively-oriented, grounded theory approach (Charmaz, 2006). Emergent themes led to the formation of a series of best practices. RESULTS/ANTICIPATED RESULTS: Common concerns included the need for more extensive training for new members; circulation of the agenda before the meeting; and the value of more structured main leadership. The members generally agreed that the breakout groups were valuable because they encouraged them to engage in hands-on responses to practical problems. One of the key epistemological findings was the consensus view that the evaluation of the EAB should be an ongoing project, as opposed to a yearly task. This serious approach to evaluation would be conducive to a process analysis of the EAB, since medical, social, economic, and cultural conditions surrounding and influencing translational science are generally in flux (e.g., the COVID-19 pandemic and the various stages in the CTSA grant). Overall, the EAB experience was quite positive for them. DISCUSSION/SIGNIFICANCE OF FINDINGS: The strongest sentiment expressed in the interviews was that the CTSA at UTMB should focus and build on its strength--the science of team science--as opposed to any concerted search for weaknesses that the term “evaluation” occasionally implies.

Birthweight and other perinatal outcomes of singletons conceived after assisted reproduction compared to natural conceived singletons in couples with unexplained subfertility: follow-up of two randomized clinical trials.

STUDY QUESTIONDoes assisted reproduction, such as ovarian stimulation and/or laboratory procedures, have impact on perinatal outcomes of singleton live births compared to natural conception in couples with unexplained subfertility?SUMMARY ANSWERCompared to natural conception, singletons born after intrauterine insemination with ovarian stimulation (IUI-OS) had a lower birthweight, while singletons born after IVF had comparable birthweights, in couples with unexplained subfertility.WHAT IS KNOWN ALREADYSingletons conceived by assisted reproduction have different perinatal outcomes such as low birthweight and a higher risk of premature birth than naturally conceived singletons. This might be due to the assisted reproduction, such as laboratory procedures or the ovarian stimulation, or to an intrinsic factor in couples with subfertility.STUDY DESIGN, SIZE, DURATIONWe performed a prospective cohort study using the follow-up data of two randomized clinical trials performed in couples with unexplained subfertility. We evaluated perinatal outcomes of 472 live birth singletons conceived after assisted reproduction or after natural conception within the time horizon of the studies.PARTICIPANTS/MATERIALS, SETTING, METHODSTo assess the possible impact of ovarian stimulation we compared the singletons conceived after IUI with FSH or clomiphene citrate (CC) and IVF in a modified natural cycle (IVF-MNC) or standard IVF with single embryo transfer (IVF-SET) to naturally conceived singletons in the same cohorts. To further look into the possible effect of the laboratory procedures, we put both IUI and IVF groups together into IUI-OS and IVF and compared both to singletons born after natural conception. We only included singletons conceived after fresh embryo transfers. The main outcome was birthweight presented as absolute weight in grams and gestational age- and gender-adjusted percentiles. We calculated differences in birthweight using regression analyses adjusted for maternal age, BMI, smoking, parity, duration of subfertility and child gender.MAIN RESULTS AND THE ROLE OF CHANCEIn total, there were 472 live birth singletons. Of the 472 singleton pregnancies, 209 were conceived after IUI-OS (136 with FSH and 73 with CC as ovarian stimulation), 138 after IVF (50 after IVF-MNC and 88 after IVF-SET) and 125 were conceived naturally.Singletons conceived following IUI-FSH and IUI-CC both had lower birthweights compared to naturally conceived singletons (adjusted difference IUI-FSH −156.3 g, 95% CI −287.9 to −24.7; IUI-CC −160.3 g, 95% CI −316.7 to −3.8). When we compared IVF-MNC and IVF-SET to naturally conceived singletons, no significant difference was found (adjusted difference IVF-MNC 75.8 g, 95% CI −102.0 to 253.7; IVF-SET −10.6 g, 95% CI −159.2 to 138.1). The mean birthweight percentile was only significantly lower in the IUI-FSH group (−7.0 percentile, 95% CI −13.9 to −0.2). The IUI-CC and IVF-SET group had a lower mean percentile and the IVF-MNC group a higher mean percentile, but these groups were not significant different compared to the naturally conceived group (IUI-CC −5.1 percentile, 95% CI −13.3 to 3.0; IVF-MNC 4.4 percentile, 95% CI −4.9 to 13.6; IVF-SET −1.3 percentile, 95% CI −9.1 to 6.4).Looking at the laboratory process that took place, singletons conceived following IUI-OS had lower birthweights than naturally conceived singletons (adjusted difference −157.7 g, 95% CI −277.4 to −38.0). The IVF group had comparable birthweights with the naturally conceived group (adjusted difference 20.9 g, 95% CI −110.8 to 152.6). The mean birthweight percentile was significantly lower in the IUI-OS group compared to the natural group (−6.4 percentile, 95% CI −12.6 to −0.1). The IVF group was comparable (0.7 percentile, 95% CI −6.1 to 7.6).LIMITATIONS, REASONS FOR CAUTIONThe results are limited by the number of cases. The data were collected prospectively alongside the randomized controlled trials, but analyzed as treated.WIDER IMPLICATIONS OF THE FINDINGSOur data suggest IUI in a stimulated cycle may have a negative impact on the birthweight of the child and possibly on pre-eclampsia. Further research should look into the effect of different methods of ovarian stimulation on placenta pathology and pre-eclampsia in couples with unexplained subfertility using naturally conceived singletons in the unexplained population as a reference.STUDY FUNDING/COMPETING INTEREST(S)Both initial trials were supported by a grant from ZonMW, the Dutch Organization for Health Research and Development (INeS 120620027, SUPER 80-83600-98-10192). The INeS study also had a grant from Zorgverzekeraars Nederland, the Dutch association of healthcare insurers (09-003). B.W.J.M. is supported by an NHMRC investigator Grant (GNT1176437) and reports consultancy for ObsEva, Merck Merck KGaA, Guerbet and iGenomix, outside the submitted work. A.H. reports grants from Ferring Pharmaceutical company (the Netherlands), outside the submitted work. F.J.M.B. receives monetary compensation as a member of the external advisory board for Merck Serono (the Netherlands), Ferring Pharmaceutics BV (the Netherlands) and Gedeon Richter (Belgium), he receives personal fees from educational activities for Ferring BV (the Netherlands) and for advisory and consultancy work for Roche and he receives research support grants from Merck Serono and Ferring Pharmaceutics BV, outside the submitted work. The remaining authors have nothing to disclose.TRIAL REGISTRATION NUMBERINeS study Trial NL915 (NTR939); SUPER Trial NL3895 (NTR4057)