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Item Embedding and Sustaining a Focus on Function in Specialty Research and Care(Wiley, 2021-01) Callahan, Kathryn E.; Boustani, Malaz; Ferrante, Lauren; Forman, Daniel E.; Gurwitz, Jerry; High, Kevin P.; McFarland, Frances; Robinson, Thomas; Studenski, Stephanie; Yang, Mia; Schmader, Kenneth E.; Medicine, School of MedicineFunction and the independent performance of daily activities are of critical importance to older adults. Although function was once a domain of interest primarily limited to geriatricians, transdisciplinary research has demonstrated its value across the spectrum of medical and surgical care. Nonetheless, integrating a functional perspective into medical and surgical therapeutics has yet to be implemented consistently into clinical practice. This article summarizes the presentations and discussions from a workshop, "Embedding/Sustaining a Focus on Function in Specialty Research and Care," held on January 31 to February 1, 2019. The third in a series supported by the National Institute on Aging and the John A. Hartford Foundation, the workshop aimed to identify scientific gaps and recommend research strategies to advance the implementation of function in care of older adults. Transdisciplinary leaders discussed implementation of mobility programs and functional assessments, including comprehensive geriatric assessment; integrating cognitive and sensory functional assessments; the role of culture, environment, and community in incorporating function into research; innovative methods to better identify functional limitations, techniques, and interventions to facilitate functional gains; and the role of the health system in fostering integration of function. Workshop participants emphasized the importance of aligning goals and assessments and adopting a team science approach that includes clinicians and frontline staff in the planning, development, testing, and implementation of tools and initiatives. This article summarizes those discussions.Item The Emerging Roles of the RNA Binding Protein QKI in Cardiovascular Development and Function(Frontiers Media, 2021-06-16) Chen, Xinyun; Yin, Jianwen; Cao, Dayan; Xiao, Deyong; Zhou, Zhongjun; Liu, Ying; Shou, Weinian; Pediatrics, School of MedicineRNA binding proteins (RBPs) have a broad biological and physiological function and are critical in regulating pre-mRNA posttranscriptional processing, intracellular migration, and mRNA stability. QKI, also known as Quaking, is a member of the signal transduction and activation of RNA (STAR) family, which also belongs to the heterogeneous nuclear ribonucleoprotein K- (hnRNP K-) homology domain protein family. There are three major alternatively spliced isoforms, QKI-5, QKI-6, and QKI-7, differing in carboxy-terminal domains. They share a common RNA binding property, but each isoform can regulate pre-mRNA splicing, transportation or stability differently in a unique cell type-specific manner. Previously, QKI has been known for its important role in contributing to neurological disorders. A series of recent work has further demonstrated that QKI has important roles in much broader biological systems, such as cardiovascular development, monocyte to macrophage differentiation, bone metabolism, and cancer progression. In this mini-review, we will focus on discussing the emerging roles of QKI in regulating cardiac and vascular development and function and its potential link to cardiovascular pathophysiology.Item Improvement in Function after Lasmiditan Treatment: Post Hoc Analysis of Data from Phase 3 Studies(Springer, 2020-12) Smith, Timothy; Krege, John H.; Rathmann, Suchitrita S.; Dowsett, Sherie A.; Hake, Ann; Nery, Emel S. M.; Matthews, Brandy R.; Doty, Erin G.; Neurology, School of MedicineIntroduction: Migraine is associated with substantial functional impairment and affects many aspects of daily life. Methods: Using data from SAMURAI and SPARTAN (double-blind, placebo-controlled, phase 3 studies) and GLADIATOR (an open-label, phase 3 study enrolling patients who had completed SAMURAI or SPARTAN), we assessed the effects of lasmiditan on migraine-related functional disability at multiple time points from 0.5 to 48 h post dose by asking patients to rate how much the migraine was interfering with normal activities. Pooled data from SAMURAI and SPARTAN (SAMURAI + SPARTAN) and data from GLADIATOR were analyzed using the intention-to-treat populations. Results: For SPARTAN + SAMURAI, significantly more patients who received lasmiditan at any dose versus placebo reported freedom from migraine-related functional disability at every timepoint from 2 h post dose, and this difference persisted to 48 h (p < 0.05). Significant differences from placebo in freedom from migraine-related functional disability commenced at 1 h post dose for lasmiditan 200 mg, 1.5 h for lasmiditan 100 mg, and 2 h for lasmiditan 50 mg. Findings from GLADIATOR supported those from SAMURAI + SPARTAN. Conclusion: All doses of lasmiditan resulted in an improvement in migraine-related functional disability that persisted to 48 h. In SAMURAI + SPARTAN, a significant difference from placebo was observed as early as 1 h post dose. TRIAL REGISTRATION AT CLINICALTRIALS.GOV: SAMURAI (NCT02439320), SPARTAN (NCT02605174), and GLADIATOR (NCT02565186).Item Longitudinal Effects of Medical Comorbidities on Functional Outcome and Life Satisfaction After Traumatic Brain Injury: An Individual Growth Curve Analysis of NIDILRR Traumatic Brain Injury Model System Data(Wolters Kluwer, 2019-09-01) Malec, James F.; Ketchum, Jessica M.; Hammond, Flora M.; Corrigan, John D.; Dams-O'Connor, Kristen; Hart, Tessa; Novack, Thomas; Dahdah, Marie; Whiteneck, Gale G.; Bogner, Jennifer; Physical Medicine and Rehabilitation, School of MedicineObjective: To explore associations of specific physical and neuropsychiatric medical conditions to motor and cognitive functioning and life satisfaction over the first 10 years following traumatic brain injury (TBI). Setting: Telephone follow-up through six TBI Model System centers. Participants: 404 individuals or proxies with TBI enrolled in the TBI Model System longitudinal study participating in 10 year follow-up. Design: Individual growth curve analysis. Main Measures: FIM™ Motor and Cognitive subscales, Life Satisfaction Scales, Medical and Mental Health Co-Morbidities Interview. Results: Hypertension, diabetes, cancers, rheumatoid arthritis, and anxiety negatively affected the trajectory of motor functioning over time. Diabetes, cancers, chronic bronchitis, anxiety, and depression negatively impacted cognitive functioning. Numerous neuropsychiatric conditions (sleep disorder, alcoholism, drug addiction, anxiety, panic attacks, PTSD, depression, bipolar disorder), as well as hypertension, liver disease, and cancers diminished life satisfaction. Other medical conditions had a negative effect on functioning and satisfaction at specific follow-up periods. Conclusion: Natural recovery after TBI may include delayed onset of functional decline or early recovery followed by progressive deterioration and is negatively affected by medical comorbidities. Results contribute to the growing evidence that TBI is most appropriately treated as a chronic medical condition complicated by a variety of comorbid conditions.Item Patterns of Functional Change Five to Ten Years after Moderate-Severe Traumatic Brain Injury(Mary Ann Liebert, Inc., 2021) Hammond, Flora M.; Malec, James F.; Corrigan, John D.; Whiteneck, Gale G.; Hart, Tessa; Dams-O’Connor, Kristen; Novack, Thomas A.; Bogner, Jennifer; Dahdah, Marie N.; Eagye, C.B.; Sevigny, Mitch; Ketchum, Jessica M.; Physical Medicine and Rehabilitation, School of MedicineThis study aims to characterize the patterns of functional change experienced between 5 and 10 years after moderate-severe traumatic brain injury (TBI). The study included TBI Model Systems national database participants (N = 372) at six sites who experienced TBI, received inpatient rehabilitation, and were followed at 5 and 10 years post-TBI. Outcome measures included self- or proxy-reported Functional Independence Measure (FIMTM) structured interview at 5 and 10 years post-TBI and domain change indices (DCIs) at 10 years to assess subjective change over the previous 5 years. When all seven FIM and subjective DCI subscales were considered together, 69% reported improvement in at least one subscale and 41% reported decline in at least one subscale; 51% reported more domains improved than declined, and 20% reported more domains declined than improved. Age at injury, post-traumatic amnesia duration, FIM, and depression and anxiety at year 5 were associated with FIM change and DCI measures. Although most persons with moderate-severe TBI do not experience widespread change from year 5 to 10 on individual FIM subscales or perceived domain-specific subscales, the vast majority do report change in one or more domains, with more improvement than decline and more change in subjective DCI than in FIM. Clinicians and researchers should be alert to the possibility of both positive and deleterious changes many years after TBI.Item Research Needs for Prognostic Modeling and Trajectory Analysis in Patients with Disorders of Consciousness(Springer, 2021) Hammond, Flora M.; Katta-Charles, Sheryl; Russell, Mary Beth; Zafonte, Ross D.; Claassen, Jan; Wagner, Amy K.; Puybasset, Louis; Egawa, Satoshi; Laureys, Steven; Diringer, Michael; Stevens, Robert D.; Curing Coma Campaign and its Contributing Members; Physical Medicine and Rehabilitation, School of MedicineBackground: The current state of the science regarding the care and prognosis of patients with disorders of consciousness is limited. Scientific advances are needed to improve the accuracy, relevance, and approach to prognostication, thereby providing the foundation to develop meaningful and effective interventions. Methods: To address this need, an interdisciplinary expert panel was created as part of the Coma Science Working Group of the Neurocritical Care Society Curing Coma Campaign. Results: The panel performed a gap analysis which identified seven research needs for prognostic modeling and trajectory analysis ("recovery science") in patients with disorders of consciousness: (1) to define the variables that predict outcomes; (2) to define meaningful intermediate outcomes at specific time points for different endotypes; (3) to describe recovery trajectories in the absence of limitations to care; (4) to harness big data and develop analytic methods to prognosticate more accurately; (5) to identify key elements and processes for communicating prognostic uncertainty over time; (6) to identify health care delivery models that facilitate recovery and recovery science; and (7) to advocate for changes in the health care delivery system needed to advance recovery science and implement already-known best practices. Conclusion: This report summarizes the current research available to inform the proposed research needs, articulates key elements within each area, and discusses the goals and advances in recovery science and care anticipated by successfully addressing these needs.Item Supporting teams to optimize function and independence in Veterans: a multi-study program and mixed methods protocol(BMC, 2018-04-20) Wang, Virginia; Allen, Kelli; Van Houtven, Courtney H.; Coffman, Cynthia; Sperber, Nina; Mahanna, Elizabeth P.; Colón-Emeric, Cathleen; Hoenig, Helen; Jackson, George L.; Damush, Teresa M.; Price, Erika; Hastings, Susan N.; Medicine, School of MedicineBACKGROUND: Successful implementation of new clinical programs depends on effectively establishing, reorganizing, or enhancing team structures and processes to coordinate the work of individuals who are interdependent in their tasks, manage relationships, and share responsibility for outcomes. However, a one-size-fits-all approach is rarely effective. In partnership with VA national clinical leaders and local clinical champions, the Optimizing Function and Independence VA Quality Enhancement Research Initiative program (Function QUERI) will evaluate efforts to implement team-based clinical programs for Veterans at risk for functional decline and disability. METHODS: Function QUERI will implement and evaluate three innovative, evidence-based clinical programs in VA medical centers: (1) a group physical therapy program for knee osteoarthritis (Group PT); (2) assisted early mobility for hospitalized older veterans (STRIDE), a supervised walking program for hospitalized older veterans; and (3) implementation of helping invested family members improve veteran experiences study (iHI-FIVES), a skills training program for caregivers of disabled Veterans. A common reason for clinical care gaps in these populations is poor communication and coordination among the many interdisciplinary providers involved in their care. To facilitate the implementation of the clinical programs, Function QUERI will evaluate the impact of complexity science-based implementation intervention to promote team readiness (CONNECT), an implementation intervention designed as a bundle of interaction-oriented activities to promote team function and readiness for change, on the implementation of clinical programs across multiple sites. The evaluation will use a mixed methods design. Group PT is a local, single-site quality improvement project where a modified CONNECT intervention will be tested to inform the remaining program implementation projects. For STRIDE and iHI-FIVES projects, we will randomize participating sites to implement the clinical program, with the CONNECT intervention or not, and will use a stepped-wedge cluster randomized trial design. DISCUSSION: Function QUERI will translate its findings across its projects to identify the contextual factors and components from CONNECT that improve team processes and function to optimize effective implementation for future rollout of VA clinical programs. Synthesizing findings within and across projects, we will specify dimensions of team characteristics and function that enhance capacity for clinical innovation and uptake of evidence-based programs.Item The Role of Tbx20 in Cardiovascular Development and Function(Frontiers Media, 2021-01-28) Chen, Yuwen; Xiao, Deyong; Zhang, Lu; Cai, Chen-Leng; Li, Bai-Yan; Liu, Ying; Pediatrics, School of MedicineTbx20 is a member of the Tbx1 subfamily of T-box-containing genes and is known to play a variety of fundamental roles in cardiovascular development and homeostasis as well as cardiac remodeling in response to pathophysiological stresses. Mutations in TBX20 are widely associated with the complex spectrum of congenital heart defects (CHDs) in humans, which includes defects in chamber septation, chamber growth, and valvulogenesis. In addition, genetic variants of TBX20 have been found to be associated with dilated cardiomyopathy and heart arrhythmia. This broad spectrum of cardiac morphogenetic and functional defects is likely due to its broad expression pattern in multiple cardiogenic cell lineages and its critical regulation of transcriptional networks during cardiac development. In this review, we summarize recent findings in our general understanding of the role of Tbx20 in regulating several important aspects of cardiac development and homeostasis and heart function.Item Who are you calling normal!: the relationship between species function and health care justice(2008-10-13T17:37:34Z) Morrell, Eric Douglas; Schwartz, Peter H.For the past 2,000 years, the medical and philosophical communities have been unable to formulate a clear conception of function. Yet, I argue that this debate has become of central importance to Western bioethics due to the role the concept of function plays within emerging health care justice models, and more broadly, within the debate surrounding universal health care in the United States. My thesis focuses on the relationship between species function and health care justice. Specifically, my position is that any workable formulation of just health care that is justified from a Rawlsian or politically liberal perspective must utilize conceptions of normal species function that are as neutral and stable as possible. I conclude by showing that Larry Wright’s evolutionarily-based teleological account of function is the most neutral and stable account of function within the philosophical canon, and utilize two case studies – idiopathic short stature and obesity – to help illustrate the applicability of Wright’s account to liberal health care justice formulations.