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The 2018 National Nursing Research Roundtable: Promoting State-of-the-Art Biobehavioral Approaches in Symptom Science Research through Inter- and Intra-Professional Collaborations

March 1 and April 4, 2018

The 2018 National Nursing Research Roundtable (NNRR) was co-sponsored by the Southern Nursing Research Society (SNRS) and the National Institute of Nursing Research (NINR), part of the National Institutes of Health. Representatives from over a dozen professional nursing societies met to discuss opportunities and challenges of interdisciplinary research collaborations and their important role in symptom science research.

NINR Director Dr. Patricia Grady provided an update on NINR research and outlined the topic of symptom science research through interprofessional collaborations. Dr. Grady noted that interdisciplinary research is increasingly important and that nurse scientists are key members of interdisciplinary research teams. Nurse scientists must keep pace with the latest techniques, initiatives, and innovations in science. They are also very adept in the translation of science to clinical care, because clinical practice—a signature example of team effort—is the foundation of nursing research.

Dr. Grady described some of the strategies that NIH and NINR have developed to foster team science. A growing number of programs, such as the All of Us Initiative and the Palliative Care Research Cooperative Group, are building infrastructure to service large-scale studies. The NINR Centers Program supports the sustainability of existing Centers of Excellence as well as new research teams to enhance interdisciplinary biobehavioral research for scientists conducting research in multiple, complex chronic conditions. Recently, the directors of NINR Centers collaborated in a pioneering effort to generate common data elements for symptom science and self-management research to facilitate the consolidation of data across studies.[1][2]

The Clinical and Translational Science Awards (CTSA) Program is a nationwide consortium of more than 50 institutions that uses multidisciplinary approaches to improve the way clinical and translational research are conducted and to enhance the efficiency and quality of research. The multiple principal director/principal investigator (PD/PI) option is an NIH-wide opportunity that supports team science. It encourages multidisciplinary collaboration among equals when that is the most appropriate way to address a scientific problem, rather than a single PD/PI.

In his keynote address, Dr. David Dinges of the University of Pennsylvania provided a more extensive discussion about real-world examples of collaborations and team science in cutting-edge biobehavioral research in symptom science. Dr. Dinges has led a wide range of interdisciplinary studies on the impact of restricted sleep on human physiology and performance, on topics such as: the effects of reduced sleep on performance and weight gain; medical resident education and patient safety; commercial motor vehicle driver health and safety; and astronaut performance and health. This research was conducted through several different types of collaborations, with various groups of colleagues from the University of Pennsylvania, other academic institutions, business, government agencies, and international agencies. These highly productive consortia yielded 103 peer-reviewed publications from 2008-2017.

Dr. Dinges discussed some of the challenges in conducting symptom science research as well as some of the components of effective symptom science studies, such as:

  • Addressing important health questions concerning chronic conditions, symptom management, health risks, disease prevention, and quality of life;
  • Collaborating with nurse scientists and other technical professionals;
  • Using mobile health (mHealth) technologies and cutting edge biological tools and approaches;
  • Having detailed knowledge of the condition and population under study;
  • Reviewing progress, problem-solving, and data control frequently (weekly, at a minimum);
  • Maintaining a timeline for data acquisition; and
  • Providing adherence and retention incentives to research participants.

The second day of the roundtable was postponed due to a weather emergency and reconvened by videoconference on April 4, 2018. Drs. Elizabeth Corwin, Leorey Saligan, and Angela Starkweather gave scientific presentations addressing the importance of interdisciplinary resources and partners in symptom science research in the context of ‘omics, a framework for collaborative research, and biobehavioral mechanisms of persistent lower back pain.

Dr. Corwin, of Emory University, discussed her venture into team science, beginning with NINR’s bold 2013 funding opportunity, “The Microbiome and Preterm Birth.” Dr. Corwin partnered with Dr. Ann Dunlop in a successful application to build on Dr. Dunlap’s research in health disparities, chronic stress, and birth outcomes. They built an interdisciplinary team that included experts in infectious disease, obstetrics and gynecology, public health, and chronic stress. Their current project focuses on minority and low-income women: groups that often report high levels of chronic stress, which has been identified as a risk factor for pre-term birth. Samples are being collected to investigate associations between oral, vaginal, and gut microbiota and pre-term birth and symptom profiles in pregnant women at two hospitals that have striking demographic (e.g., education, income, marital status) and health (e.g., pre-term birth rates, prenatal antibiotic and marijuana use) differences.

Dr. Corwin described how the expertise of research team members from other disciplines changed the course of the project. With a co-investigator, she obtained a supplement from the NIH Common Fund's Metabolomics Program that brought junior scientists, fellows, and students into the project. The supplement supported a retrospective analysis of samples, which has identified metabolites associated with chronic stress and pre-term birth. Funding has also been awarded to add epigenetic investigations to the microbiome study. A multi-investigator program project on environmental toxicants is providing data to evaluate the impact of prenatal exposure to toxicants on pre-term birth and newborn development. In addition, Dr. Corwin and her colleagues are participating in the NIH Environmental Influences on Child Health Outcomes (ECHO) Program, a nationwide initiative that exemplifies team science and aims to develop science-based, innovative solutions for real-world problems.

Dr. Corwin endorsed nurse scientists in clinical settings as essential research partners, who can position themselves in leadership roles in research teams. She stated that “nurses hold a lot of the cards,” because of their close contact with patients that fosters trust and their ability to identify what is important to patients.

Dr. Saligan, Chief of the Symptom Biology Unit in NINR’s Division of Intramural Research, described the basic and clinical research in his division. Dr. Saligan and his colleagues aim to elucidate the interactions between molecular mechanisms underlying symptoms and symptom clusters, as well as environmental factors, and their collective contribution to individual health outcomes. His group conducts research on cancer treatment-related fatigue—a common, costly, and disabling symptom—to understand its causes and trajectories, and to identify potential therapeutic targets. Dr. Saligan cited evidence that severe fatigue across diseases and illnesses is driven by similar biological mechanisms, so fatigue biomarkers might help address fatigue in more than one condition.

Dr. Saligan discussed the development of his collaborative framework to advance symptom science, which began with a matrix of mentors: senior intramural scientists at NIH and extramural experts in different aspects of cancer-related fatigue. Through additional collaborations, the National Cancer Institute’s intramural researchers gave him access to their patients and the NIH Clinical Center’s Rehabilitation Medicine Service recommended the addition of objective measures of physical fatigue, such as hand grip for skeletal strength and actigraphy for sleep activity, that are associated with self-reported fatigue. NIH Intramural Program post-doctoral and post-baccalaureate fellows (including nursing school graduates) and special volunteers bolstered the conduct of research. More efficient data collection was supported by software from colleagues in Pittsburgh, which facilitated hand grip and computer-based testing of cognitive function while research participants waited for clinical appointments.

Dr. Saligan collaborated with the Translational Immunology Laboratory at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), finding that expression levels of the inflammatory molecular markers tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL decoy receptor increased in patients with persistent fatigue, but not in patients without fatigue. A collaboration with bioinformaticians at Harvard University and the University of Oviedo in Spain found that genes for glutamate receptors were highly predictive for persistent fatigue, one year after radiation therapy. Further investigation in patient samples showed that elevated glutamate receptor gene expression was specific to the fatigue group, in comparison with non-fatigue patients. Colleagues at the National Institute of Mental Health (NIMH) are using the same glutamate receptor genes as markers for depression and their increased expression can be mediated by ketamine treatment. With the help of his NIMH colleagues, Dr. Saligan is conducting a proof of concept study of ketamine or its equivalent, Midazolam, to alleviate cancer treatment-related fatigue. He acknowledged that his numerous collaborations outside of nursing have optimized the rigor of his research.

Rounding out the formal presentations, Dr. Starkweather of the University of Connecticut described the utility of the NIH Symptom Science Model (NIH-SSM) for phenotyping complex symptoms and biomarker discovery through team science. The investigation may begin with a cellular model of the symptom, then a biomarker is identified that can predict the symptom. Next, the model is tested in a population to see if it holds true. She acknowledged the bidirectionality of investigation between animal models and clinical populations, followed by subsequent clinical trials of interventions in various populations.

Dr. Starkweather’s interest in understanding pain sensitivity in chronic pain conditions began when she saw numerous patients in the emergency department with lower back pain (LBP) who did not find relief with treatment. Through a collaboration with colleagues at the University of Maryland, Baltimore, Dr. Starkweather added quantitative sensory testing to her research protocol, which also gave her trainees exposure to new techniques. She has adopted more complex tools to distinguish between temperature, mechanical, and pressure pain thresholds. In a clinical trial for patients with persistent LBP, thermal pain was a predictor of chronic pain at the 12-week follow-up and psychosocial factors played a greater role in chronic pain at the 18-week follow-up.

Dr. Starkweather noted that symptom trajectories are central to symptom science, especially across the lifespan, and that mHealth can help to monitor distressing symptoms over time. For example, distinguishing between chronic pain and episodic pain will determine whether analgesics should be prescribed for periodic or “as needed” dosage. As technology improves, the tracking and prediction of emerging symptoms will become more precise.

Dr. Starkweather offered that interprofessional collaborations move research forward and contribute to precise and accurate analyses that inform clinical practice. Success of collaborative teams is demonstrated not only by numbers of publications, but also new ideas, clinical significance, dissemination of results to clinical settings, and branching off in new, exciting, and stimulating research areas. Dr. Starkweather recommended examining common goals together; this approach, with her professional society, helped her to identify unresolved LBP as an important research topic. Good communication characterizes the strength of the team and positions it for agreement on next steps; a strong team is more attractive to new members.

Dr. Starkweather closed with the main messages she gleaned from her participation in the Roundtable:

  • Collaboration is critical at the beginning of a project: for conjuring ideas, study design, implementation plans, and clinical applications
  • Context and environment are essential for understanding symptoms
  • Symptom trajectories have a significant impact on patient outcomes
  • Research methods should be considered in the interpretation of study findings and implications for the real world
  • Collaboration and data-sharing are essential for advancing symptom science

The discussion portion of the Roundtable concentrated on: 1) the practice, education, and policy implications of employing state-of-the-art biobehavioral approaches in symptom science research through inter- and intra-professional collaborations, and 2) strategies that NNRR organizations could use to highlight the importance of inter- and intra-professional collaborations to promote state-of-the-art biobehavioral approaches in symptom science research. ‘Omics research opens new pathways of knowledge and preparation for the next generation of nurses, to help personalize health care and to develop precision nursing interventions. In addition to NINR’s numerous training opportunities, interdisciplinary collaborations help students to learn the importance of biological mechanisms in symptom science. Guidance from professional organizations, such as annual lists of research priorities, can connect nurse scientists with patient populations.

[1] Redeker NS, Anderson R, Bakken S, Corwin E, Docherty S, Dorsey SG, Heitkemper M, McCloskey DJ, Moore S, Pullen C, Rapkin B, Schiffman R, Waldrop-Valverde D, Grady P. Advancing Symptom Science Through Use of Common Data Elements. J Nurs Scholarsh. 2015 Sep;47(5):379-88.

[2] Moore SM, Schiffman R, Waldrop-Valverde D, Redeker NS, McCloskey DJ, Kim MT, Heitkemper MM, Guthrie BJ, Dorsey SG, Docherty SL, Barton D, Bailey DE Jr, Austin JK, Grady P. Recommendations of Common Data Elements to Advance the Science of Self-Management of Chronic Conditions. J Nurs Scholarsh. 2016 Sep;48(5):437-47.

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