Congratulations to our 2013 Pilot Project Awardees!
Susan Buchholz, PhD
Rajeev Garg, MD
Hannah Lundberg, PhD
Masako Mayahara, PhD
Rick Sumner, PhD
Dustin Wakeman, PhD
Title: Pilot Study of a Physical Activity Text Messaging Intervention for a Foodservice Employee Population
PI: Susan Buchholz, PhD, RN, professor, Department of Adult Health and Gerontological Nursing, College of Nursing, Rush University Medical Center
Co-Is: Diana Ingram, PhD, MPH, JoEllen Wilbur, PhD, RN, & Louis Fogg, PhD
Abstract: Physical inactivity is ranked fourth as a risk factor for mortality and contributes to increased risk for chronic diseases. At particular risk for physical inactivity and chronic diseases are low-income working adults. These low-income wage earners include food service workers who represent a growing industry, but are among the lowest wage earners in the country. Worksite clinics are now being used to address health concerns of employees, including health promotion and chronic disease prevention programs. With the exponential growth and widespread usage of cell phones and text messaging, there is a new generation of technology via mobile health (mHealth) available for health promotion. A small number of studies have shown that physical activity text messages can be effectively used to help adults improve their physical activity. However, the use of text messaging within the context of promoting physical activity for low-income working adults is understudied. We recently conducted focus groups at three clinics with low-income patients to assess text message use and develop physical activity text messages. They indicated familiarity with and use of text messaging and enthusiasm for the technology as a means of delivering a physical activity intervention. They also generated a data bank of over 170 physical activity text messages. The purpose of the proposed mHealth project is to use this physical activity text message data bank in a study that will test the feasibility and effect sizes of delivering a text message intervention (Text4Walking) to increase physical activity in food service employees. Using a one-group 12-week longitudinal design, employees (N=32) aged 30 to 65 will be recruited from a food service worksite, that is a catering facility that prepares food for retail and airline customers. In this intervention study, guided by a Physical Activity Health Promotion Framework, participants will wear accelerometers to measure their daily steps, and they will receive 36 text messages (three per week), over a 12 week period of time. They will also receive feedback when they text in their daily steps once weekly, as well as receive feedback on their steps during three study calls. The behavioral outcomes measured at baseline and 12 weeks will be adherence to physical activity (using an accelerometer and self-report), aerobic fitness (step test) and body composition (BMI and waist circumference). A repeated-measures multivariate analysis of variance (RM-MANOVA) will be performed at baseline and 12 weeks. We hypothesize that we will have significant within group improvement on physical activity and physical fitness outcomes, and body composition will remain stable, from baseline to 12 weeks. If the data validate our hypothesis, we will have identified a potentially innovative and efficient strategy for delivering a physical activity program in the context of a food service worksite. These data will provide pilot data for a larger randomized controlled trial.
Title: Assessment of Cerebral Blood Flow by Quantitative Perfusion MRI in Patients With Spontaneous Intracerebral Hemorrhage and Its Effect on DWI Abnormalities
PI: Rajeev Garg, MD, assistant professor, Department of Neurological Sciences, Rush University Medical Center
Co-Is: Drs. Tom Bleck, MD; Robert Dawe, MD; Miral Jhaveri, MD; Bichun Ouyang, PhD
Abstract: Secondary ischemic injury as noted by diffusion-weighted imaging abnormalities (DWI) on magnetic resonance imaging (MRI) of the brain is common after spontaneous intracerebral hemorrhage (ICH). A reduction in cerebral perfusion pressure has been hypothesized as a mechanism for these DWI abnormalities. MRI of the brain with quantitative perfusion-weighted imaging (PWI) and DWI would assess this mechanism. Hypothesis: Our hypothesis is that reductions in cerebral perfusion pressure as assessed by PWI do occur in patients with spontaneous ICH during active treatment and cause the development of DWI abnormalities. Methodology: Consecutive patients with primary ICH meeting criteria will be approached for consent. Admission data including socio-demographic background, relevant stroke risk factors, and treatment variables will be recorded prospectively. An MRI of the brain with PWI and DWI will be obtained within 24 hours of admission. The PWI and DWI imaging will be reviewed separately by two attending neuroradiologists for the presence of abnormalities. The prevalence of perfusion changes and its association with DWI lesions will be examined. Significance: Correlation between a reduction in cerebral perfusion pressure and DWI abnormalities would provide evidence of a potential mechanism for secondary ischemic injury in patients with ICH. Monitoring of cerebral perfusion pressure may be a novel target for intervention to prevent DWI and potentially improve outcomes in these patients.
Title: Patient-Specific Prediction of Total Knee Arthroplasty in Vivo Performance
PI: Hannah Lundberg, PhD, assistant professor, Department of Orthopedic Surgery, Rush University Medical Center
Co-Is: Joshua Jacobs, MD and Markus Wimmer, PhD
Abstract: There is a fundamental gap in understanding how knee joint patient-specific motions and activities affect polyethylene stress and surface wear in total knee arthroplasty (TKA). Continued existence of this gap represents an important problem because until it is filled, prediction of how prostheses will fare for an individual patient in the long-term remains largely incomprehensible. The long-term goal is to improve implant longevity for individual patients through a comprehensive model that predicts multiple TKA failure mechanisms. The overall objective of this application is to investigate the TKA loads, polyethylene stresses, and surface wear under patient specific walking, and to compare the model to simulator-tested components. The central hypothesis is that patient- specific walking patterns result in different implant contact stress and wear than generic walking patterns specified by industry testing standards. The rationale underlying the proposed research is that, after identifying how physiological TKA contact conditions affect wear, TKA designs of any material and under any patient behavior can be modulated to promote contact conditions best for implant longevity. The hypothesis will be tested under two specific aims: 1) Determine TKA contact conditions and polyethylene stresses for patient-specific and generic walking patterns; and 2) Develop and validate a TKA computational wear model and predict TKA surface wear for patient-specific and generic walking patterns. Under the first aim, a validated TKA force model together with finite element analysis (FEA) will be used to determine contact conditions and polyethylene stresses during walking for a group of TKA patients and for generic walking from standardized simulator input. Under the second aim, a FEA-based TKA wear model will be used to predict wear for patient-specific and generic walking patterns. The approach is innovative because it will link FEA wear simulations to a validated force model which will allow TKA wear modeling of patient-specific kinematics and kinetics. This will allow robust future studies of implant, surgeon and patient factors that influence TKA wear under physiological conditions. These studies are important because polyethylene wear is dependent on sliding direction, sliding velocity, force and contact area, all of which are dependent on knee joint kinematics and kinetics of the individual patient. The proposed research is significant because it is the first step towards developing a validated comprehensive patient-specific model capable of predicting long-term TKA failure under multiple damage mechanisms.
Ultimately, such knowledge has the potential to inform TKA design and pre-clinical testing to help reduce the growing burden of TKA revision surgery in the United States.
Title: Impact of Digital Pain and Analgesic Diary in Reducing Medication Error in a Hospice Setting
PI: Masako Mayahara, PhD, assistant professor, College of Nursing, Rush University Medical Center
Abstract: As utilization of home hospice care increases, more informal caregivers (e.g., family members and friends) are becoming involved in patient pain management, regardless of their skills and knowledge. There is growing concern over caregivers who have to manage complex analgesic regimens at home. Lack of adherence to analgesic regimens has been associated with poor pain control. Additional support is needed for informal caregivers to be successful in managing pain at home. Technological advances may offer tools to help nurse case managers to monitor informal caregivers’ administration of analgesics in the home hospice without being present. Therefore, the purpose of this study is to develop and test the feasibility of a digital application to be used by caregivers to record patient pain and administration of analgesics and used by nurse case managers to monitor caregiver administration of analgesics. The specific aims are to: (1) develop a digital pain and analgesic monitor application using a tablet platform (iPad) to facilitate nurse case manager monitoring of patient pain and informal caregivers’ analgesic administration; (2) assess the feasibility of using this application by investigating the frequency with which informal caregivers record data (pain and analgesic) and both nurse case managers’ and informal caregivers’ satisfaction with the application; (3) examine the changes resulting from use of the digital pain and analgesic monitor application in informal caregiver outcomes (confidence in caregiving, barriers to pain management, depression and adherence to the analgesic regimen) and patient outcomes (depression, quality of life and control of pain) from baseline to 3 weeks after the baseline. The development of this digital application will be informed by an expert panel of nurse case managers, an advisory panel of informal caregivers and a technical expert. The feasibility of this digital pain and analgesic monitor application will be tested with 22 informal hospice caregiver and cancer patient dyads from a hospice and palliative care agency. These findings will inform the development of a future controlled trial.
Title: Bone Mineralization Pilot Project
PI: Rick Sumner, PhD, professor, Department of Anatomy and Cell Biology, Rush University Medical Center
Abstract: The purpose of this pilot project is to test the hypothesis that an existing rat model of induced intracortical bone remodeling can be used to study bone quality. Variations in the organic and inorganic phases of the bone matrix affect bone as a material. The material properties, in combination with the distribution of the matrix in space (e.g., cortical bone geometry or trabecular bone architecture) determine the overall strength, stiffness and energy-to-failure of the bone as a tissue and organ. Cortical bone makes up ~80% of the total skeletal mass and contributes significantly to the mechanical strength of long bones.
Because bone remodeling continues throughout life it is important to examine how the new bone which forms in the adult skeleton matures, particularly in light of the existence of FDA-approved anti-catabolic and anabolic treatments for various metabolic bone diseases including osteoporosis, with several novel drugs also under development. A major limitation for the research community in understanding how drugs or other agents affect bone matrix properties in the adult skeleton is the lack of a small animal model for studying cortical bone remodeling. We propose to use a rat model in which cortical resorption is induced by feeding lactating females a low calcium diet and bone formation occurs when the dams are returned to a normal diet at weaning.
However, little is known about the bone formed during recovery except that it is lamellar and not fully mineralized within three weeks. To characterize the model, we will determine the rate of matrix maturation at the three cortical bone surfaces (endocortical, periosteal and intra-cortical) and at the trabecular bone surface (Aim 1). We are taking this approach because we recently showed that rates of mineralization vary at different bone surfaces in nonhuman primates and it is important to determine if the rat model replicates this finding.
The primary endpoint will be the rate of matrix maturation using backscatter scanning electron microscopy, Fourier transform infrared microspectroscopy and fluorescent microscopy. Sclerostin antibody is a bone forming agent in Phase III trials for osteoporosis. We recently discovered that this agent also accelerates intracortical bone matrix mineralization in a nonhuman primate model. In Aim 2, we will determine if the pace of intra-cortical matrix maturation is accelerated in the rat model during treatment with sclerostin antibody.
Demonstration that the rat model replicates our previous work in a primate model will be important for model validation. If the project is successful, the new model will provide an in vivo means to assess cortical bone matrix maturation. Thus, we anticipate validating a new in vivo approach to assess mechanisms of how bone quality can be altered in the adult skeleton.
Title: Clinical Translation of iPSC Cells in Parkinson's Disease
PI: Dustin Wakeman, PhD, assistant professor; Department of Neurological Sciences, Rush University Medical Center
Co-I: Jeffrey Kordower, PhD
Abstract: Parkinson’s disease (PD) is a debilitating, progressive, neurodegenerative disorder afflicting more than 6.3 million individuals worldwide, with a staggering 1.5 million suffering patients in the United States alone. More than 55,000 new PD patients are diagnosed each year in the United States, and this number is on the rise with the ever-increasing aging population. Stem cells may provide a solution to many of the known or suspected problems of neural transplantation for PD. Human induced pluripotent stem cell derived dopamine neurons (iPSC-DA) offer a number of advantages, including being expandable relatively indefinitely as well as being immunologically matched to the patient, and therefore are extremely promising as an alternative cellular substrate for transplantation. While our group and others have shown considerable functional therapeutic promise using human embryonic stem cell (HESC) and iPSC derived dopamine neurons in rodent models for PD (Kriks et al, 2011), iPSC-DA cell therapies have never been successfully tested pre-clinically in parkinsonian monkeys, thus, there is a critical need to determine if they will provide functional benefits in the best pre-clinical model. We recently showed extensive HESC-DA cell survival in the striatum of parkinsonian monkeys (Kriks et al., 2011) as proof of concept for pluripotent cell therapy in PD. Demonstrating the functional efficacy and structural correlates of this innovative approach utilizing iPSC-DA neurons will allow us to advance our program through essential preclinical steps and close a critical gap-in-knowledge towards human clinical trials.
Kriks S, Shim JW, Piao J, Ganat YM, Wakeman DR, Xie Z, Carrillo-Reid L, Auyeung G, Antonacci C, Buch A, Yang L, Beal MF, Surmeier DJ, Kordower JH, Tabar V, Studer L. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease. Nature. 2011 Nov 6.