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Predicting Early Failure in Total Knee Arthroplasty: A Critical Review of Oxinium Femoral Components

Fri, 05/20/2016 - 3:30pm

Introduction: Retrospectively, it has been shown that significant patient-reported pain 6 months following total knee arthroplasty (TKA) is associated with a 7 times greater revision rate at 5 years. Our goal is to use the FORCE-TJR registry to prospectively evaluate if postoperative pain and function scores can predict increased revision rate 5 years following TKA. Our preliminary analyses have focused on one implant reported by Australia to have a significantly high 5-year revision rate: Oxinium femoral components. Materials and Methods: FORCE-TJR matched implant catalog numbers to the international implant library to define TKA patients who received oxinium femoral components and all other implants. We defined 12-month KOOS pain and function (SF PCS) for patients with the study implant and all others (n=9187). Age, BMI, sex, pre-TKA pain, function, low back pain severity, and Charlson comorbidity index were compared for patients with moderate pain (KOOS pain<75) vs. minimal pain (KOOS pain>75) at 12 months postoperatively. Results: We observed that 27% of oxinium patients reported moderate pain vs. 21% of patients receiving all implants at 12 months postoperatively. Compared to patients with minimal pain, moderate pain patients had greater pre-op pain (KOOS=37 vs. 50; p< 0.0002), poorer pre-op function (PCS=30 vs. 33; p<0.04), and more moderate to severe low back pain (52% vs. 24%; p<0.027). In addition, high 12-month pain patients had poorer 12-month function (PCS=37 vs. 45; p<0.0000). Conclusion: These preliminary results indicate that moderate pain at 12-months post operatively is associated with poorer functional gain following TKA. Surgeons should recognize and potentially intervene on this group if improvement in their ultimate functional gain is desired. By continuing to follow this group of oxinium patients we will be able to determine if early pain and decreased function following TKA is associated with an increased revision rate.

Sulforaphane Treatment of Children with Autism Spectrum Disorder

Fri, 05/20/2016 - 3:30pm

Abstract This clinical trial in autism spectrum disorder (ASD) tests a nontoxic approach to therapy of ASD.

Background: Direct treatment of underlying mechanisms in ASD is limited. Cellular dysfunction in ASD may involve a number of related metabolic pathways. A clinical clue may be found in the “fever effect” in ASD, in which febrile illness dramatically but temporarily ameliorates disordered behavior. Fever stimulates heat shock proteins (HSP) and cellular stress responses that may ultimately lead to improved synaptic function and increased long-range connectivity. The expression of gene transcription by NFE2L2 (Nrf2), which is reduced in ASD, may also increase during fever. Sulforaphane (SF), an isothiocyanate obtained from 3-day-old broccoli sprouts, induces HSP and Nrf2 as well as “cell-protective” responses. SF has several possible modes of action that may benefit ASD through common cellular mechanisms underlying heterogeneous phenotypes. SF crosses the blood brain barrier and is bioavailable orally.

Preliminary data: In a randomized, double-blind, placebo-controlled pilot trial in 44 male adolescents and adults (13-30 years), results showed SF was well tolerated without significant side effects. On average, participants on SF (particularly those with a history of fever effect) showed significantly more improvements in ASD symptoms than placebo participants. Significant improvements for SF participants included social interaction, aberrant/abnormal behavior, repetitive/stereotypical behavior, and verbal communication.

Current study: Our randomized, double-blind, placebo-controlled phase-2 clinical trial at UMass has three aims: To determine: (1) if orally administered SF has measurable effects in children (ages 3-12 years) with ASD; (2) if treatment with sulforaphane is safe and well tolerated; (3) To elucidate cellular biomarkers that support the mechanisms of action of SF in ASD. We hypothesize that SF will have positive effects, and that these effects will be more marked and lasting in the developing – compared to the mature – brain.

Bioavailability of the Antimalarial Drug Artemisinin Delivered Orally as Dried Leaves of Artemisia annua: the Role of Solubility and Protein.

Fri, 05/20/2016 - 3:30pm

Malaria treatment using orally consumed dried leaves of the artemisinin producing GRAS plant Artemisia annua has recently shown promise. Previously we showed, oral consumption of A. annua dried leaves (DLA) yielded >40 times more artemisinin in the blood of mice than treatment with pure artemisinin. Using the Caco-2 cell culture model of the human intestinal epithelium, we also showed that compared to pure artemisinin, digested DLA doubled the permeability (Papp). Here, using simulated human digestion, we show that artemisinin solubility is about seven times higher in digestates of DLA than in digestates of pure artemisinin, likely contributing to its enhanced bioavailability. Digestion with pure artemisinin combined with levels of essential oils comparable to that in DLA increased the solubility of artemisinin 2.5 times indicating essential oils play a role in increasing artemisinin solubility. Interestingly, increasing the starting concentration of artemisinin in Caco-2 transport studies did not alter Papp. Considering malaria affects mostly young children and about 60% of the population experiences DLA as unpleasant tasting, we also tested several protein rich foods as potential flavor-masking agents for their effects on bioavailability. We showed that while taste was masked, peanuts and a peanut-based paste used to treat malnutrition, PlumpyNut, reduced artemisinin and flavonoid levels in simulated digestates, respectively, likely decreasing their bioavailability. Experiments to further investigate the role of several compounds such as camphor, a principle component of the essential oil fraction, and flavonoids on artemisinin solubility and bioavailability are ongoing. The results of these experiments are helping to explain the increased bioavailability afforded by DLA seen in mice.

Community-based Participatory Research to Promote Healthy Diet and Nutrition and Prevent and Control Obesity among African Americans: A Literature Review

Fri, 05/20/2016 - 3:30pm

The literature on community-based participatory research (CBPR) approaches for promoting healthy diet, nutrition, and preventing and controlling obesity in African American communities was systematically reviewed.

CBPR studies of diet, nutrition, and weight management among African Americans were identified from 1989 through October 31, 2015 using PubMed and CINAHL databases and MeSH term and keyword searches.

A total of 16 CBPR studies on healthy diet, nutrition, and weight management among African Americans were identified; outcome evaluation results were available for all but two. Of the remaining 14 studies, 11 focused on adults, 1 on children, and 2 on both children and adults. Eight studies employed CBPR methods to address diet, nutrition, and weight management in church settings. Four had a cluster randomized controlled design. Others had a pre-post test, quasi-experimental, or uncontrolled design. Only one study addressed four levels of the socioecological model; none addressed all five levels of the model. The identified studies indicate that CBPR approaches can be effective for promoting healthy diet, nutrition, and weight management among African American adults but there is a need for additional studies with rigorous study designs that overcome methodologic limitations of many existing studies. There is only limited evidence for the effectiveness of CBPR approaches for promoting healthy eating and weight control among African American children and adolescents

To address health disparities, additional CBPR studies are needed to promote healthy diet, nutrition, and weight management in African American communities. Of particular interest are multilevel CBPR studies that include interventions aimed at multiple levels of the socioecological model.

Workplace Predictors of Perceived Quality of Care in Nursing homes

Fri, 05/20/2016 - 3:30pm

Nursing home quality of care (QOC) is a matter of public concern and public policy. Higher nurse-to-patient ratios have been shown to decrease rates of adverse outcomes. Positive nurse-doctor relationships also have a positive effect, which might translate to other clinical staff, such as nursing aides, who perform the majority of direct care tasks in nursing homes. This cross-sectional study examined whether workplace factors in nursing homes were associated with QOC as evaluated by staff members themselves. Surveys were distributed to personnel in 24 nursing home facilities in the Northeast U.S. A total of 1463 respondents provided ratings of QOC and 14 work environment features. Analyses included correlations, Cronbach’s alpha, and principal components analyses (with rotation) to examine psychometric properties of predictor scales and reduce multicollinearity. A multivariable model of QOC was built using all potential workplace factors to determine which factors contribute to self-reported QOC, with removal of those covariates that were not significant (p>0.05), decreased the model fit, or showed a confounding effect (>15% change in other coefficients). The final model showed that perceived commitment and obstacles to safe-lifting programs, respect and support between coworkers and supervisors, adequacy of staffing, physical exertion, safety climate, and psychological demand, were significant contributors to staff-assessed QOC. Nursing homes should consider cultivating these work environment characteristics for the benefit of both direct-care staff and the residents for whom they provide care.

The Effect of Mobile Self-monitoring on Self-care Behaviors in Heart Failure and COPD Patients: A Feasibility Study

Fri, 05/20/2016 - 3:30pm

Exacerbations of heart failure (HF) and chronic obstructive lung disease (COPD) are among the most costly illnesses. Patient recognition of changes in symptoms cueing imminent exacerbation is poor. Innovative strategies to improve patient symptom recognition, self-care behaviors and treatment seeking are necessary to improve overall health outcomes.

The aim of this pilot study was to test the feasibility of a wireless health monitoring device and cell phone app in 10 patients (5 with COPD and 5 with HF). This collaborative multidisciplinary study is innovative in its inclusion of the patient as an active partner in the use of technology to monitor changes in physiologic indicators to alert them to baseline status changes and guide self-care decision-making. The nurse-engineer team worked to develop devices that met the data collection needs of the research team, while being mindful of comfort and body image concerns of the patient. Additionally, the engineers provided the nurse researchers essential training on troubleshooting technology problems in the field. Weekly home visits with participants provided ongoing feedback that impacted design decisions and revisions throughout the data collection period.

Data were collected on self-care (SCHFI) at enrollment and post intervention. Participants had a mean age of 67.7 + 11.9 years, EF of 26.5 + 11.8, 60% male, 70% married. Mixed between-within subjects’ analysis of variance was conducted to test the impact of the intervention on the participant’s self-care scores. There was no significant interaction between group and time, Wilk’s Lambda = .97, F (1, 17) = .46, p = .51. There was no significant main effect for time Wilk’s Lambda = .94, F (1, 17) = 1.14, p = .30. Self-care maintenance (31 vs 31.7), management (49.2 vs 63) and confidence (58.2 vs 58.7) scores were inadequate at each time but did increase after intervention.

A Reduced Order Model For Efficient Physiological Flow Analysis In Aneurysms by Proper Orthogonal Decomposition

Fri, 05/20/2016 - 3:30pm

Simulating physiological flows using computational fluid dynamics (CFD) remains to be computationally expensive and difficult for clinical usage because of the physiological flow and geometrical complexity involved in patient specific situations. We use the reduced order modeling (ROM) of such systems with high nonlinearity and geometrical non-uniformity to replace the full, nonlinear model with a low-degrees of freedom ROM model. We construct ROM models by the proper orthogonal decomposition (POD) method to estimate the flow-induced wall shear stress (WSS) and pressure loading of a simplified abdominal aortic aneurysm and a bifurcation cerebral aneurysm. This method allows us to investigate a wide range of different physiological flow parameters without conducting the computationally expensive CFD simulations repetitively, which is promising for clinical usage.

We obtain a set of snapshots from a set of flow simulations with multiple variable parameters, called the training set. The training set should be simulated in a parameter space that contains all the physiological parameters of interest. We show that both the velocity and pressure distributions are well reconstructed when compared with the exact values with a small number of modes. A mesh-less shell model is used to estimate the aneurysm sidewall’s in-plane stresses. Sidewalls with non-uniform thickness are considered to study the influence of local weakness on the aneurysm’s risk of failure. We found that the sensitivity of the material’s strength to the local weakness depends on the aneurysms sidewall’s Gaussian curvatures, the curvature to thickness ratio and the distribution of the flow loading. It is therefore critical to describe the distribution of curvature and thickness accurately when estimating the in-plane stress of aneurysms.

Utilizing the Green Nursing Project Initiative to Educate Nurses about Health Effects Related to Exposure of Chemicals Contained in Household and Personal Care Products and to Inspire Them to Take Action

Fri, 05/20/2016 - 3:30pm

Consumers are exposed to a variety of environmental chemicals including carcinogens, reproductive toxins, and endocrine disrupting chemicals from everyday use of common household and personal care products. Evidence supports concern that exposures to low doses or the combination of low doses of chemicals can pose a health risk for the general population as well as for vulnerable populations. Gaps exist in translating this information to the public and helping people understand the health effects related to chemical exposures and personal actions they could take to reduce exposures.

There are 2.6 million nurses in the U.S. who have direct access to numerous patient populations. Educating and utilizing nurses as a conduit for information-sharing related to environmental health issues could fill the gap, influence health outcomes, and contribute to sustainable communities.

A Speaker’s Bureau was constructed under the Central Mass Health Literacy Project to facilitate community access to health literacy topics. The Green Nursing Project is an initiative to educate hundreds of nurses about Environmental Health Literacy topics and Inspire them to take Personal and Professional Action. The Green Nursing Project includes Hands-on Interactive Workshops to introduce participants to chemicals in consumer products, adverse health effects, and risk reduction strategies.

Implantable Microenvironments to Capture Stable-to- Aggressive Tumor Transition

Fri, 05/20/2016 - 3:30pm

Clinical stability occurs when cancers reach a state where the disease neither advances nor regresses. Tumors can remain in this state for multiple years before progressing to more aggressive phenotypes. The mechanisms for maintaining a stable state and the factors that contribute to tumor activation are poorly understood. We hypothesized that an implantable biomaterial scaffold would be able to isolate a population of stable tumor cells that could then be used to study the transition to an aggressive phenotype. In this work we developed a tunable and highly controlled, porous acrylamide scaffold and subcutaneously implanted them in immunodeficient (NSG) mice. Prior to implantation scaffolds were seeded with a variety of different cell types. Specifically, human bone marrow stromal cells were supplemented with mouse stromal cells genetically engineered to express human cytokines to promote the generation of different tissue microenvironments in the scaffolds. After implantation the mice received an orthotopic injection of either human breast or prostate cancer cells. The tumors were allowed to generate metastases to the scaffolds and other tissues. Scaffolds were transplanted to non-tumor bearing mice once the tumor burden became exhaustive to the host to allow for further study of the microenvironment. The role of immune cells on the tumor microenvironment was also explored. Human peripheral blood mononuclear cells were isolated from donors and injected intravenously prior to transplantation. Bioluminescent imaging was used to capture tumor growth in vivo over a ten week period. The scaffolds were analyzed via immunohistochemical staining on thinly sectioned tissue and intact tissue cleared samples to characterize the tissue microenvironment and its effect on tumor progression. Our work has demonstrated the application of implantable tissue engineered microenvironments to study the phenomena of tumor stability in vivo and has uncovered some potentially important factors that drive the transition from stable to aggressive tumors.

Prospective Relations between Red Blood Cell ω-6 and ω-3 Fatty Acid Composition and Cognitive Function among Older Puerto Rican Adults

Fri, 05/20/2016 - 3:30pm

Objectives: To examine the association between red blood cell (RBC) ω-6 and ω-3 fatty acid (FA) composition and cognitive function over 2-y follow-up among older U.S. mainland Puerto Ricans.

Methods: Data are from the Boston Puerto Rican Health Study (74% female; 57±8 y). RBC membrane FA status was ascertained at baseline. Individual FA were expressed as a percentage of total FA identified. Cognitive function was measured at baseline and at 2-y using the Mini-Mental State Exam (MMSE), where a higher score ranging from 0-30 indicates better function. Cognitive impairment was defined as MMSE scores ≤21, ≤23, and ≤24 for those with less than a 9th grade education, a 9th to 12th grade education, and some college education or higher, respectively. Relations between FA and MMSE scores were examined in 946 participants and incidence of cognitive impairment among those considered to be cognitively normal at baseline (n=639).

Results: In multivariate models additionally adjusted for baseline MMSE, total ω-6 FA (quartiles) were associated with lower MMSE score at 2-y (P-trend=0.003). Total ω-3 FA were positively (P-trend=0.04) and the ω-6:ω-3 ratio inversely (P-trend=0.007) related to 2-y MMSE, but these relationships attenuated with adjustment for baseline score. The incidence of cognitive impairment at follow-up was 22%. In multivariate models, a 1% increase in total ω-6 FA related to a 9% greater incidence of cognitive impairment [RR=1.09 (95% CI: 1.00, 1.18), P=0.04]. Total ω-3 FA were inversely related to incident cognitive impairment [RR=0.92 (0.81 to 1.05), P=0.21], whereas the ω-6:ω-3 ratio was positively associated [RR=1.12 (95% CI: 0.98, 1.26), P=0.08].

Conclusions: An objective biomarker of ω-6 FA consumption was associated with poorer cognitive function and incidence of cognitive impairment over 2-y follow-up, suggesting that greater intakes of food sources of ω-6 FA may play a role in cognitive decline among older U.S. mainland Puerto Ricans.

Poster Session Program: 2016 UMass Center for Clinical and Translational Science Research Retreat

Fri, 05/20/2016 - 3:30pm

Poster Session Program for the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

View poster abstracts

Race/Sex Group Modification of the Association between Allostatic Load and Depression: Findings from the National Health and Nutrition Examination Survey, 2005-2010

Fri, 05/20/2016 - 3:30pm

Objective: We assessed whether the relationship between depression and chronic stress as measured in allostatic load (AL) differs by race and sex among US black and white adults.

Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2010, we examined race/sex modification of the relationship between AL and depression in black and white women and men aged 18-64 years (n=6431). AL scores, ranging from 0-9, were calculated using 9 cardiovascular, metabolic, and immunologic biomarkers; scores ≥ 4 were considered “high-risk”. Depression was assessed using the PHQ-9; scores ≥ 10 indicate clinical depression. Logistic regression models estimated odds of elevated depressive symptoms as a function of AL for each race/sex group; age and socioeconomic status were included as covariates in each model. All analyses were weighted to represent U.S. adults.

Results: The association between AL and depression was strongest among white women (OR=2.1, 95% CI: 1.5, 3.0), followed by black men (OR=1.7 95% CI: 1.0, 2.9), and not statistically significant among black women (OR=1.1 95% CI: .60, 2.0) or white men (OR=1.4 95% CI: .82, 2.5).

Conclusions: Our findings that the association between AL and depression was strongest and statistically significant only among white women and black men despite black women having the highest mean AL and depression scores suggests a measure of psychological resistance to chronic stress among those coping with intersecting pressures of systemic race and gender-based discrimination. These results also suggest that social inequality may shape the manner in which chronic stress is expressed. Further research should explore other potential racialized and gendered manifestations of chronic stress in order to better understand social factors influencing health inequity.

Plasma PLP Concentration and Depressive Symptomatology, over time, in older Latino Adults

Fri, 05/20/2016 - 3:30pm

Background: Low vitamin B-6 status has been linked to depressive symptomatology. However, most studies have been cross-sectional and may not have controlled for relevant confounders. Few studies have examined this association in Latino populations at high risk for major depression.

Design: We used two-level hierarchical linear regression models (HLM) for continuous outcomes. Level-1 data included three measures of participant’s depressive symptomatology collected at baseline, 2y follow-up and 5y follow-up. Participants constituted level-2 data. Vitamin B-6 was associated with depressive symptomatology across these time points.

Objective: We examined the longitudinal association of vitamin B-6 status with depressive symptomatology across 3 time points over ~ 5-7 y in a cohort of older Puerto Rican adults, a population previously identified to be at high risk for depressive symptomatology and clinical depression.

Results: Plasma pyridoxyl-5’-phosphate (PLP) concentration, a time-varying predictor, was significantly associated with depressive symptomatology. Study participants with PLP deficiency, vs. optimal PLP, had higher baseline depressive symptoms (22±14, vs. 20±13); this differential remained constant over time and persisted after controlling for age, sex, education, BMI, smoking and alcohol use, other relevant nutritional factors, perceived stress, stressful life events and allostatic load; and use of antidepressant medication. However, PLP concentration was not associated with the rate of change in depressive symptomatology over time.

Conclusions: Suboptimal plasma PLP is associated with higher depressive symptomatology in older Puerto Rican adults and this appears to persist over time. Our data suggest that identification and treatment of vitamin B-6 deficiency may be a useful preventive and intervention approach in this population.

Piloting Signs of Safety: A Deaf-Accessible Toolkit for Trauma and Addiction

Fri, 05/20/2016 - 3:30pm

The Deaf community - a minority group of 500,000 Americans who use American Sign Language (ASL) - experiences trauma and addiction at rates double to the general population. Yet, there are no evidence-based treatments that have been evaluated to treat trauma, addiction, or other behavioral health conditions among Deaf people.

Current evidence-based treatments fail to meet the needs of Deaf clients. One example is Seeking Safety, a well-validated therapy for people recovering from trauma and addiction. Seeking Safety includes a therapist guide and client handouts for 25 therapy sessions, each teaching clients a safe coping skill. When Seeking Safety was used with Deaf clients, unique barriers were revealed with regard to the client materials: they were presented in complex English instead of ASL, nor sensitive to Deaf people’s culture, social norms, and history of oppression.

To address these barriers, Dr. Anderson assembled a team of Deaf and hearing researchers, clinicians, filmmakers, actors, artists, and Deaf people in recovery to develop Signs of Safety, a Deaf-accessible toolkit to be used with Seeking Safety. Signs of Safety is comprised of a therapist companion guide and population-specific client materials, including visual handouts and ASL teaching stories on digital video, which present key learning points via an “educational soap opera.”

Dr. Anderson is currently leading a pilot study of Signs of Safety. Preliminary results show that participants are reporting symptom reduction from baseline to follow-up and high levels of satisfaction with the model, giving us the confidence to further pursue this line of research.

The Academic Medical Center’s Perspective on the Physician Scientist

Fri, 05/20/2016 - 2:15pm

As part of the mini-symposium entitled "The Challenge of Maintaining our Physician-Scientist Workforce," Dr. Volturo discusses balancing the needs of the clinical enterprise and optimizing hospital finances with the needs of the physician scientist workforce.

The Challenge of Maintaining our Physician-Scientist Workforce (Rare Breed/Endangered Species): Epidemiology & Anecdotes

Fri, 05/20/2016 - 2:15pm

As part of the mini-symposium entitled "The Challenge of Maintaining our Physician-Scientist Workforce," Dr. Moore Simas discusses the epidemiology of physician scientists in the modern era with a focus on specialty-based and demographic issues.

Skeletal Muscle Function Changes with Aging and Exercise: From the Myosin Molecule to the Whole Muscle

Fri, 05/20/2016 - 2:15pm

As part of the mini-symposium entitled "Advancing Translational Research at the UMass Amherst Center for Personalized Health Monitoring," Dr. Miller's presentation highlights current research initiatives on muscle function changes with aging and exercise.

Physician- Scientist Initiative: AAIM Third Consensus Conference on the Physician-Investigator Workforce

Fri, 05/20/2016 - 2:15pm

As part of the mini-symposium entitled "The Challenge of Maintaining our Physician-Scientist Workforce," Dr. Garcia presents the results of the recent consensus conference of the Association of Academic Internal Medicine on this issue.

Voyager Therapeutics - A Spinout from UMass Gene Therapy and RNAi Technologies

Fri, 05/20/2016 - 2:15pm

As part of the mini-symposium entitled "Shark Tank-UMass Spin-out Life Sciences Start-ups," Dr. Gao discusses an example of UMass life sciences technology that has been spun out into a start-up company -- Voyager Therapeutics from UMass Worcester.

Advancing Translational Research at the UMass Amherst Center for Personalized Health Monitoring

Fri, 05/20/2016 - 2:15pm

This is the moderator's introductory presentation for the mini-symposium entitled "Advancing Translational Research at the UMass Amherst Center for Personalized Health Monitoring," in which she discusses the mission of the Center, which is to advance life sciences research to improve human health.