Research Spotlight

Posted April 15th 2017

Using health promotion guidelines for persons with disabilities to develop and evaluate a physical activity program for individuals with multiple sclerosis: A feasibility study.

Simon Driver Ph.D.

Simon Driver Ph.D.

Dixon-Ibarra, A., M. Nery-Hurwit, S. Driver and M. MacDonald (2017). “Using health promotion guidelines for persons with disabilities to develop and evaluate a physical activity program for individuals with multiple sclerosis: A feasibility study.” Eval Program Plann 61: 150-159.

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The Health Education for Persons with Multiple Sclerosis (HEMS) program was developed in response to the need for interventions aimed at increasing physical activity for individuals with Multiple Sclerosis (MS). It was developed and evaluated using Drum and colleagues (2009) guidelines for implementing health promotion programs for individuals with disabilities. The purpose of this feasibility study is to describe the development, implementation, and evaluation of the HEMS program. Thirteen individuals with MS completed the 8-week health education program. A mixed method approach for evaluation was implemented (i.e., survey and focus groups). Process and resource feasibility demonstrated that over half of the participants attended at least 80% of the weekly sessions. Focus group data provided valuable feedback for future iterations of the program including critiques on the delivery, content, and group support provided. Outcome evaluation showed increases in self-efficacy (survey), improvements in theoretical constructs (focus groups), and increased physical activity (focus groups). Results show that health promotion programs for persons with MS can improve physical activity and related constructs. Next steps will be to revise, implement, and reevaluate the HEMS program in a larger randomized control trial.


Posted April 15th 2017

Process for developing rehabilitation practice recommendations for individuals with traumatic brain injury.

https://bhslibrary.tamhsc.edu/wp-content/uploads/2016/04/Shahid-Shafi-M.D..jpg

Shahid Shafi M.D.

Callender, L., R. Brown, S. Driver, M. Dahdah, A. Collinsworth and S. Shafi (2017). “Process for developing rehabilitation practice recommendations for individuals with traumatic brain injury.” BMC Neurol 17(1): 54.

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BACKGROUND: Attempts at measuring quality of rehabilitation care are hampered by a gap in knowledge translation of evidence-based approaches and lack of consensus on best practices. However, adoption of evidence-based best practices is needed to minimize variations and improve quality of care. Therefore, the objective of this project was to describe a process for assessing the quality of evidence of clinical practices in traumatic brain injury (TBI) rehabilitative care. METHODS: A multidisciplinary team of clinicians developed discipline-specific clinical questions using the Population, Intervention, Control, Outcome process. A systematic review of the literature was conducted for each question using Pubmed, CINAHL, PsychInfo, and Allied Health Evidence databases. Team members assessed the quality, level, and applicability of evidence utilizing a modified Oxford scale, the Agency for Healthcare Research and Quality Methods Guide, and a modified version of the Grading of Recommendations, Assessment, Development, and Evaluation scale. RESULTS: Draft recommendations for best-practice were formulated and shared with a Delphi panel of clinical representatives and stakeholders to obtain consensus. CONCLUSION: Evidence-based practice guidelines are essential to improve the quality of TBI rehabilitation care. By using a modified quality of evidence assessment tool, we established a process to gain consensus on practice recommendations for individuals with TBI undergoing rehabilitation.


Posted April 15th 2017

Multicenter Systems Analysis of Human Blood Reveals Immature Neutrophils in Males and During Pregnancy.

Nicole Baldwin Ph.D.

Nicole Baldwin Ph.D.

Blazkova, J., S. Gupta, Y. Liu, B. Gaudilliere, E. A. Ganio, C. R. Bolen, R. Saar-Dover, G. K. Fragiadakis, M. S. Angst, S. Hasni, N. Aghaeepour, D. Stevenson, N. Baldwin, E. Anguiano, D. Chaussabel, M. C. Altman, M. J. Kaplan, M. M. Davis and D. Furman (2017). “Multicenter systems analysis of human blood reveals immature neutrophils in males and during pregnancy.” J Immunol 198(6): 2479-2488.

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Despite clear differences in immune system responses and in the prevalence of autoimmune diseases between males and females, there is little understanding of the processes involved. In this study, we identified a gene signature of immature-like neutrophils, characterized by the overexpression of genes encoding for several granule-containing proteins, which was found at higher levels (up to 3-fold) in young (20-30 y old) but not older (60 to >89 y old) males compared with females. Functional and phenotypic characterization of peripheral blood neutrophils revealed more mature and responsive neutrophils in young females, which also exhibited an elevated capacity in neutrophil extracellular trap formation at baseline and upon microbial or sterile autoimmune stimuli. The expression levels of the immature-like neutrophil signature increased linearly with pregnancy, an immune state of increased susceptibility to certain infections. Using mass cytometry, we also find increased frequencies of immature forms of neutrophils in the blood of women during late pregnancy. Thus, our findings show novel sex differences in innate immunity and identify a common neutrophil signature in males and in pregnant women.


Posted April 15th 2017

A phase II study of combined ridaforolimus and dalotuzumab compared with exemestane in patients with estrogen receptor-positive breast cancer.

Joanne L. Blum M.D.

Joanne L. Blum M.D.

Baselga, J., S. M. Morales, A. Awada, J. L. Blum, A. R. Tan, M. Ewertz, J. Cortes, B. Moy, K. J. Ruddy, T. Haddad, E. M. Ciruelos, P. Vuylsteke, S. Ebbinghaus, E. Im, L. Eaton, K. Pathiraja, C. Gause, D. Mauro, M. B. Jones and H. S. Rugo (2017). “A phase ii study of combined ridaforolimus and dalotuzumab compared with exemestane in patients with estrogen receptor-positive breast cancer.” Breast Cancer Res Treat: 2017 Mar [Epub ahead of print].

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PURPOSE: Combining the mTOR inhibitor ridaforolimus and the anti-IGFR antibody dalotuzumab demonstrated antitumor activity, including partial responses, in estrogen receptor (ER)-positive advanced breast cancer, especially in high proliferation tumors (Ki67 > 15%). METHODS: This randomized, multicenter, international, phase II study enrolled postmenopausal women with advanced ER-positive breast cancer previously treated with a nonsteroidal aromatase inhibitor (NCT01234857). Patients were randomized to either oral ridaforolimus 30 mg daily for 5 of 7 days (once daily [qd] x 5 days/week) plus intravenous dalotuzumab 10 mg/kg/week or oral exemestane 25 mg/day, and stratified by Ki67 status. Due to a high incidence of stomatitis in the ridaforolimus-dalotuzumab group, two sequential, nonrandomized, reduced-dose cohorts were explored with ridaforolimus 20 and 10 mg qd x 5 days/week. The primary endpoint was progression-free survival (PFS). RESULTS: Median PFS was 21.4 weeks for ridaforolimus 30 mg qd x 5 days/week plus dalotuzumab 10 mg/kg (n = 29) and 24.3 weeks for exemestane (n = 33; hazard ratio = 1.00; P = 0.5). Overall survival and objective response rates were similar between treatment arms. The incidence of drug-related, nonserious, and serious adverse events was higher with ridaforolimus/dalotuzumab (any ridaforolimus dose) than with exemestane. Lowering the ridaforolimus dose reduced the incidence of grade 3 stomatitis, but overall toxicity remained higher than acceptable at all doses without improved efficacy. CONCLUSIONS: The combination of ridaforolimus plus dalotuzumab was no more effective than exemestane in patients with advanced ER-positive breast cancer, and the incidence of adverse events was higher. Therefore, the combination is not being further pursued.


Posted April 15th 2017

The Killer Immunoglobulin-Like Receptor Dilemma: How Do We Harness the Power of Killer Immunoglobulin-like Receptors?

Medhat Z. Askar M.D.

Medhat Z. Askar M.D.

Askar, M. (2017). “The killer immunoglobulin-like receptor dilemma: How do we harness the power of killer immunoglobulin-like receptors?” Biol Blood Marrow Transplant 23(4): 535-536.

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Alloreactive natural killer (NK) cells have been reported to significantly impact allogeneic hematopoietic cell transplantation (HCT) outcomes. How the interactions between killer immunoglobulin-like receptors (KIR) and HLA influence human NK cell functions has been demonstrated by elegant in vitro experiments [1]. Since the early 2000s, the published literature has been populated with numerous studies investigating the association between KIR genotype/haplotype and clinical outcomes of HCT, both independently and in the context of interaction with corresponding HLA ligands. Meanwhile, additional models for KIR modulation of NK cell functions have been proposed [2]. The method of KIR typing adds another layer of complexity in studying the associations between KIR and HCT outcomes. Most published studies in this domain rely on logistically attractive genotyping methods that allow identification of all KIR genes from archived DNA samples collected routinely for HLA typing and typically tested in large batches. In contrast, flow cytometry–based phenotyping and RNA-based transcription profile testing require freshly collected samples and are more technically involved. Leung et al. have demonstrated significant heterogeneity in the level of KIR expression by NK cells with more than 10-fold difference observed among individuals with similar genotype; they have also demonstrated that transcripts of only 2 of 12 KIR genes tested (KIR2DL3 and KIR3DL2) were consistently detectable by real time PCR [3]. These results suggest the potential relevance of phenotyping, rather than genotyping, in KIR-based selection of HCT donors. Lastly, different alleles of a KIR gene were reported to have different functional properties, such as licensing capability, durability of surface expression after ligand interaction, and intracellular signaling [4].