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Optimizing Microfluidic Design for Cell Separation

Tue, 05/16/2017 - 4:45pm

To evaluate the performance of various designs of crossflow filtration microfluidic devices, blood flow was modeled using computational fluid dynamics software (COMSOL Multiphysics). Velocity profiles were generated and used to analyze four critical design parameters: pillar size, pillar shape, gap size, and wall length. These parameters were optimized to yield greatest flow from an unfiltered main channel into two filtered side channels of the device, thereby maximizing filtration capacity.

Devices containing pillars of 10 µm diameter yielded a significantly greater filtration capacity than devices with pillars of 20 µm diameter. Flow patterns from the main channel to the side channels were not significantly affected when circular, octagonal, and hexagonal pillars were compared; however, use of triangular and square pillars caused a reduction in side channel flow rates. Side channel velocities consistently improved as gap sizes were increased from 3.0 µm to 8.0 µm; however, 3.5 µm gaps were included in the final design for the purpose of separating red and white blood cells. Backflow prevention walls were placed at bends in the device and were systematically lengthened until all backflow was eliminated.

Following optimization of the microfluidic device, two prototypes were prepared: a polydimethylsiloxane (PDMS) device with glass backing and a silicon device with PDMS backing. The filtration capacity of these devices were tested using polystyrene microspheres with sizes corresponding to those of red and white blood cells. In both prototypes, between 73 and 75% of small microspheres were consistently filtered into the side channels. Silicon-PDMS devices demonstrated better retention of large microspheres in the main channel and less microsphere agglomeration than did PDMS-glass devices. The benefits of silicon-PDMS devices, however, came at the cost of a difficult fabrication process.

Polymeric Nanoparticles for Targeted Combination Treatment of Temozolomide Resistant Glioblastoma Multiforme (GBM)

Tue, 05/16/2017 - 4:45pm

Glioblastoma Multiforme (GBM) is an aggressive cancer that originates from astrocytes and spreads to spinal cord and other parts of the brain. Increase in replication of glial cells leads to advantageous mutations in the tumor. According to the cancer statistics from 2015 about 15,320 deaths were reported due to GBM. Five-year survival is less than 5% making GBM a dreadful form of cancer. Current treatment involves complex invasive surgery, followed by chemotherapy and radiation. The goal of this study is to develop a combination therapy to treat GBM using Poly (lactic-co-glycolic acid) (PLGA) nanoparticles encapsulated with two drugs namely gefitinib and GSK461364, each with a unique target. Gefitinib is a Tyrosine Kinase inhibitor, which competes for ATP-binding site of EGFR-TK. GSK461364 is a Polo-like Kinase (PLK-1) inhibitor that blocks the G2/M transition in tumor cell cycle. These distinct hydrophobic drugs are tested on U-87 MG (human malignant glioma) cell line. PLGA is attached to Polyethylene glycol (PEG), which is conjugated to transferrin receptor binding peptide. These transferrin peptides bind to transferrin receptors (TfR) or CD71 and enable the entry of PLGA-PEG nanoparticles across the Blood Brain Barrier (BBB). Results of characterization, TEM, SEM images, in vitro drug release profiles, stability, cytotoxicity assay, flow cytometry data of uptake of the nanoparticles will be presented.

Transcriptional Regulation of Cardiac Remodeling in a Porcine Model with Validation in Human Subjects

Tue, 05/16/2017 - 4:45pm

Introduction: The majority of new atrial fibrillation (AF) cases occur in elderly patients with cardiac remodeling (CR) in the setting of structural heart disease and heart failure (HF). We leveraged a unique animal model to identify cardiac microRNAs (miRNAs) and gene regulatory mechanisms that drive this process.

Methods: We prospectively quantified atrial expression of 48 miRNAs by high-throughput qRT-PCR in 15 pigs with right-atrial pacing-induced heart disease (5 pigs with AF/severe HF, 5 pigs with AF/mild HF, and 5 control pigs) as well as in 21 patients (11 with AF and CR and 10 controls) undergoing cardiac surgery. CR and HF were defined through a metric of left atrial volume index, BNP and ejection fraction. MiRNA levels were normalized to global mean and expression compared across pig subtypes and between the two human groups.

Results: In the porcine model, miR-208b was upregulated at week 1 (ΔCT= -3.9, pT = -5.5, pT = -1.5, pT = -1.5, p<0.05) after induction of AF compared to sinus rhythm animals. The increase persisted at week 3 compared to week 1 (ΔCT = -1.5, p<0.05). Similarly, humans with AF and HF had higher tissue expression of miR-208b compared to controls (ΔCT = -1.5, p<0.05).

Conclusions: Dysregulation of miR-208b is confirmed in our porcine model and is validated in humans. Prior studies have identified miR-208b in both myosin isoform switching and conduction disease. We theorize that dysregulation of miR-208b may play a critical role in atrial structural remodeling and vulnerability to AF.

Pediatric Critical Care Transfusion and Anemia Expertise Initiative

Tue, 05/16/2017 - 4:45pm

Introduction/Hypothesis: Despite evidence that a lower hemoglobin threshold is safe in hemodynamically stable children, studies have shown that transfusion thresholds in practice are higher, exposing these children to the morbidity and mortality associated with RBC transfusion. Therefore, there is increased need for evidence-based blood management strategies for clinicians caring for critically ill children.

Methods: The Pediatric Critical Care Transfusion and Anemia Expertise Initiative has brought together a group of 49 international experts in pediatric transfusion/critical care in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI), to conduct a consensus conference series on pediatric critical care blood management. The methodology is modeled after that used in the Pediatric Acute Lung Injury and Consensus Conference and will create consensus statements via a structured process outlining existing data in RBC transfusion. Novel features include engagement with implementation science experts to enable consensus uptake.

Results: Two of the three expert meetings have been successfully conducted. Ten topics were identified and include recommendations on indications for RBC transfusion in critically ill children 1) based on hemoglobin triggers in the general population, 2) based on physiological triggers in the general population, 3) traumatic brain injury, 4) congenital heart disease, 5) hematologic/oncologic disease, 6) respiratory failure, 7) shock, 8) bleeding, 9) extracorporeal support, and 10) alternative processing. The systematic review was performed. The short text recommendations were generated, discussed at the second meeting and will undergo voting using the RAND UCLA Appropriateness Method to achieve consensus.

Conclusions: The TAXI consensus series is the first consensus series to convene international and multidisciplinary experts to create consensus statements on transfusion practices to improve outcomes and safety for critically ill children at risk for, or who require, RBC transfusions.

Home Interventions for Older Adults with Asthma

Tue, 05/16/2017 - 4:45pm

Older asthmatic adults are more likely to experience respiratory failure than younger adults and children with asthma. Older adults spend up to 90% of their time in the home where many allergens are found. While there is sufficient evidence that home interventions improve the health of asthmatic children, there is insufficient evidence for the effectiveness of home interventions with adults. Our research evaluates the hypothesis that multi-trigger, multifaceted home interventions improve respiratory health and reduce home asthma triggers for older adults.

Methods: We evaluated the effectiveness of conducting interventions in the homes of 86 diverse, low-income older adults (age 62 or above) diagnosed with asthma, residing in public and private subsidized housing. The two largest populations include Hispanics (45%) and Asians (20%). Data was collected on respiratory health outcomes before and after the home intervention (questionnaires on symptoms, quality of life, medication use, doctor/ER/hospital visits, and exhaled nitric oxide (eNO) a measure of lung inflammation). Asthma trigger activities (ATAs) and exposures were also evaluated before and after the home intervention (questionnaire, home survey, measurement of nitrogen dioxide (NO2), dust samples for rodent and cockroach allergens, biomarker for cigarette smoke exposure (urinary cotinine).

Interventions included education on asthma and environmental triggers; environmental remediation including mattress/pillow covers, provision of vacuum with HEPA filters, green cleaning supplies and changes in home as needed (commercial cleaning, integrated pest management, gas stove replacement, mold remediation).

Results: Significant health improvements were found in the following areas: number of doctor visits due to asthma, quality of life indicators including symptom and activity levels, and asthma control test.

Inhibition of Insulin Amyloid Formation by Small Organofluorine Molecules

Tue, 05/16/2017 - 4:45pm

Many human diseases, including Alzheimer’s disease (AD) and diabetes mellitus type II (DM) have been connected to protein misfolding and the formation of highly ordered fibrillar protein aggregates called amyloids. DM is characterized by an overproduction of insulin to the point of insulin resistance in the body. The protein deposits in the AD-affected brain is related to the aggregation of tau protein and amyloid β (Aβ) peptide. Amyloid fibrils and their oligomeric precursors are known to be cytotoxic inducing neurological cell death. Recent clinical studies have suggested a link between Alzheimer’s disease and DM based on the fact that DM patients have double the risk of developing Alzheimer’s disease. It is believed that the increased risk of heart disease and stroke linked to DM causes further damage to blood vessels that eventually target the brain. Due to the continued rise of both diseases among aging adults, there is considerable interest in eluciditating the similarities and differences in the mechanism of amyloid formation of insulin and Aβ and understanding how the oligomeric state of the two peptides affect each other’s aggregation and role. Our group has already designed and experimentally tested a broad variety of small molecules, including organofluorines that effectively inhibit the self-assembly of Aβ. As an extension of these earlier studies the same group of organofluorine molecules are being tested for their inhibitory activity in the formation of insulin fibrils. The aggregation of insulin with/without these potential inhibitors at 37°C and pH=7.4 are followed by a kinetic Thioflavin T (ThT) fluorescence assay and visualized by Atomic Force Microscopy (AFM). The small molecule-insulin interactions are also investigated by electrospray mass spectrometry (HR-ESI-MS).

The Effects of Yoga on Adults with Type II Diabetes: A Systematic Review and Meta-analysis

Tue, 05/16/2017 - 4:45pm

Objective: The purpose of this meta-analysis was to examine the effects of yoga for glycemic control among adults with type II diabetes (T2DM).

Methods: Comprehensive electronic databases searches located 2,559 unique studies with relevant key terms. Studies were included if they a) evaluated a yoga intervention to promote T2DM management, b) used an objective measure to assess glycemic control at post-intervention, and c) had follow-up length or post-test of at least 8 weeks from baseline. Studies were excluded if yoga was not the primary intervention focus (e.g., if yoga was part of a mindfulness-based intervention). Independent raters coded participant, design and methodological characteristics and intervention content. Weighted mean effect sizes and 95% confidence intervals (CI) were calculated.

Results: Total 23 studies with 2,473 participants (M age = 53 years; 43% women) met eligibility criteria. Most studies (18) were conducted in India; 2 were conducted in England, 1 in Cuba, 1 in Indonesia, and 1 in Iran. Compared with controls, yoga participants were successful in improving their HbA1c (d+ = 0.37, 95% CI = 0.18, 0.55; k = 14), fasting blood glucose (d+ = 0.57, 95% CI = 0.38, 0.76; k = 19), postprandial blood glucose (d+ = 0.29, 95% CI = 0.17, 0.41; k = 11). Yoga was also associated with significant improvements in lipid profile, blood pressure, body mass index and waist/hip ratio. Overall, studies satisfied an average of 41% of the methodological quality (MQ) criteria; however, MQ score was not associated with any outcome (ps >.05).

Conclusion: Yoga improved glycemic outcomes and other risk factors for complications in adults with T2DM relative to a control condition. Additional studies with longer follow-ups are needed to determine the long-term efficacy of yoga for adults with T2DM.

Companion Diagnostics for Breast Cancer Chemotherapeutics

Tue, 05/16/2017 - 4:45pm

Chemotherapy plays a major role in breast cancer treatment. However, not every chemotherapeutics is appropriate for each cancer due to the person’s individual cancer characteristics and whether the patient has developed chemoresistance to a particular drug. In this research, the InVitro-Q is used to detect subtle differences in tumor cell proliferation post-treatment with four-breast cancer chemotherapeutics used: paclitaxel, docetaxel, nocodazole, and cytochalasin B. Our multi-well cell-based sensor that can monitor real-time biological changes in living cells, such as mass redistribution, and viscoelasticity. This system provides unique kinetic information regarding the phenotypic change in the cells post treatment. Each drug induces apoptosis by targeting a different mechanism of action. Each drug was assayed for 48h with MCF-7 or SK-Br-3 breast cancer cells, and data collected. Post analysis we created quantitative projection regarding the efficacy of each drug on the specific cancer type.

Imaging Probes for Detecting Inflammation in the Mouse Model of Type 1 Diabetes

Tue, 05/16/2017 - 4:45pm

Non-invasive imaging of early signs of inflammation of endocrine pancreas is of importance due to a generally late clinical diagnosis of type 1 diabetes (T1D). Seventy-80% of insulin producing beta-cells could be already lost prior to the onset of clinical symptoms. Therefore, monitoring these early changes including increased vascular permeability of pancreas and activation of pro-inflammatory signaling pathways will aid in early diagnosis and timing of therapy. We have developed and tested superparamagnetic nanoparticles (NPs) with strong photoacoustic signal for detecting potential permeability changes in the pancreas of streptozotocin (STZ)- induced mouse model of T1D. These biocompatible gold/iron-oxide NPs enable application of multi-modality photoacoustic (PA) and magnetic resonance (MR) imaging to investigate the extent of NP accumulation in the pancreas. In addition, we have investigated the spatial distribution of nanoparticles in the endocrine and exocrine of pancreas using electron microscopy techniques. Our initial time-dependent histology results demonstrate the influx of macrophages and neutrophils as the first responders to pancreatic damage as well as activation of the NF-ҡB signaling pathway, which plays a central role in the inflammation of the islets. We recorded a significantly stronger PA signal in the pancreas of STZ-treated mice compared to control mice, which indicate higher accumulation of the NPs in mice with chemically induced diabetes. The potential use of a combination of clinically available imaging modality (MRI) and emerging high-resolution/high sensitivity PA makes this approach feasible for clinical translation. Furthermore, the safety of these imaging modalities makes them ideal for both initial diagnosis of diabetes in individuals at risk of T1D and for longer term noninvasive monitoring of the response to therapy.

Exploring the Contributions of Local Health Departments in Land Use and Transportation Policy: Implications for Cross-sector Collaboration

Tue, 05/16/2017 - 4:45pm

Introduction: Transportation and land use policies can impact physical activity. Local health departments (LHDs) are encouraged to participate in land use and transportation policy processes, which are outside their traditional expertise. Cross-sector collaborations are needed, yet stakeholders’ perceptions of LHD involvement are not well-understood. This paper explores (1) the perceived value of LHD participation in transportation and land use decision-making and (2) potential contributions of LHDs to these processes among relevant stakeholders.

Methods: Qualitative data were analysed from 49 semi-structured interviews conducted in 2015 and 2016. Participants were professionals representing land use planning (n=13), transportation/public works (n=11), public health (n=19), bike and pedestrian advocacy (n=4), and municipal administration (n=2). Two analysts conducted thematic analysis.

Results: All respondents reported that LHDs offer valuable contributions to transportation and land use policy processes. Seven specific contributions were identified (inter-rater agreement 91%). Participants described LHD knowledge of the built environment impact on health (n=44); ability to incorporate the public health evidence-base and best practices into built environment processes (n=23); and ability to articulate the impact of land use and transportation decisions on vulnerable populations (n=8). Other potential contributions included increasing public support through public education (n=27) and convening partnerships within the community and across municipal departments (n=35) to advance policy buy-in and enactment. Ability to analyse a range of data that could inform policy (n=41) and providing resource support (e.g., grant writing, offering technical assistance (n=20)) were also described.

Conclusions: LHDs can leverage their strengths to foster cross-sector collaborations that promote community physical activity opportunities. The results of these interviews are being used to inform the development of sustainable capacity building models for LHD involvement in built environment decision-making.

Developing a Community-Based Screening and Referral Mechanism for Atrial Fibrillation in Low Resource Settings: “Smartphone Monitoring for Atrial Fibrillation in Real-Time – India (SMART-India)”

Tue, 05/16/2017 - 4:45pm

BACKGROUND: Atrial fibrillation (AF), the world’s most common arrhythmia, often goes undetected and untreated in low-resource communities, including India. Moreover, AF is an important risk factor for stroke, which plagues an estimated 1.6 million Indians annually. As such, early detection of AF and management of high-risk patients is critically important to decrease stroke burden in individuals with AF.

OBJECTIVE: The objectives of this study are to evaluate the age- and sex-stratified epidemiology of AF in Anand District, Gujarat India; characterize the profile of individuals who are diagnosed with AF; and determine the performance of two mobile technologies for community-based AF screening.

METHODS: We built on findings from our feasibility study and leveraged two novel technologies as well as an existing community health program to screen 2,500 people from 60 villages of Anand District. A single-lead EKG and a pulse-based app was used to screen each individual for AF 3 times over a period of 5 days. Participants with suspected arrhythmias were referred at a local tertiary-care hospital for further evaluation and follow up with a cardiologist. Participants diagnosed with AF were initiated on treatment as deemed appropriate by the cardiologist.

ANALYTICAL PLAN: Age- and sex-stratified AF prevalence for AF will be calculated using survey weights to estimate population prevalence. Sociodemographic and clinical factors associated with AF will be evaluated using multivariable regression methods. Performance of each mobile technology in detecting AF will be evaluated by measuring sensitivity, specificity, and discriminative ability while considering a 12-lead EKG interpretation as gold-standard.

CONCLUSIONS: Effective approaches for leveraging state-of-the-art technology to develop a screening and referral mechanism for AF in low-resource settings requires active participation with community partners and health workers.

Caste Matters: Perceived Discrimination among Women in Rural India

Tue, 05/16/2017 - 4:45pm

Purpose: To examine the relationship of caste and class with perceived discrimination among pregnant women from rural western India.

Methods: A cross-sectional survey was administered to 170 pregnant women in rural Gujarat, India, who were enrolled in a longitudinal cohort study. Everyday Discrimination Scale and Experiences of Discrimination questionnaires were used to assess perceived discrimination and response to discrimination. Based on self-reported caste, women were classified to three categories with increasing historical disadvantage: General, Other Backward Castes (OBC), and Scheduled Caste or Tribes (SC/ST). Socioeconomic class was determined using standardized

Kuppuswamy scale. Regression models for count and binomial data were used to examine association of caste and class with experience of discrimination and response to discrimination.

Results: 68% of women experienced discrimination. After adjusting for confounders, there was a consistent trend and association of discrimination with caste but not class. In comparison to General Caste, lower caste (OBC, SC/ST) women were more likely to 1) experience discrimination (OBC OR: 2.2, SC/ST: 4.1; p-trend: 0.01), 2) have a greater perceived discrimination score (OBC IRR: 1.3, SC/ST: 1.5; p-trend: 0.07), 3) accept discrimination (OBC OR: 6.4, SC/ST: 7.6; p-trend: < 0.01), and 4) keep to herself about discrimination (OBC OR: 2.7, SC/ST: 3.6; p-trend: 0.04).

Conclusion: The differential experience of discrimination by lower caste women in comparison to upper caste women and their response to such experiences highlight the importance of studying discrimination to understand existing caste-based disparities.

In Vivo Protection with Human Monoclonal Antibody S315 following Challenge with Diphtheria Toxin

Tue, 05/16/2017 - 4:45pm

Background: Morbidity and mortality from Corynebacterium diphtheriae is reduced by prompt administration of equine-derived diphtheria anti-toxin (DAT), which is in short supply worldwide. MassBiologics has developed a human monoclonal antibody (S315) to diphtheria toxin to provide a safer alternative to DAT and address critical supply issues. S315 prevents toxin binding to its putative host receptor and S315 pre-mixed with toxin increased survival in a guinea pig model of intoxication. To further evaluate the ability of S315 to provide in vivo protection, we established a post-exposure treatment model.

Methods: Female Hartley guinea pigs (300-350g) were challenged subcutaneously with diphtheria toxin (0.03 to 0.09 Lf, limit of flocculation) to identify the minimum lethal dose. To evaluate anti-toxin efficacy, DAT or S315 was administered five hours post-toxin challenge and animals monitored for 30 days for signs of illness (lethargy, dehydration, weak limbs). Serum anti-diphtheria toxin antibodies were measured by ELISA and Vero cell toxin neutralization assays.

Results: The minimum lethal toxin dose was 0.09 Lf. To determine the protective dose of DAT, 0.2 IU, 1.0 IU or 5.0 IU was administered intravenously post-toxin challenge (n=4/cohort). All 0.2 IU or 1.0 IU DAT-treated animals died, while one animal treated with 5.0 IU survived. DAT was subsequently evaluated at 5.0 IU, 10 IU, and 20 IU and compared to a cohort receiving 3.5 mg of S315. All untreated animals died within 72 hours and all antibody-treated animals survived. Dehydration was observed more frequently in the 5 IU and 10 IU DAT cohorts compared to the 20 IU and S315 cohorts.

Conclusions: Treatment with S315 after diphtheria toxin exposure is protective; further studies will define a minimum effective dose of S315. This model mimics the route and timing of anti-toxin treatment in humans and provides a rigorous preclinical evaluation of a human antibody replacement for equine DAT.

Recruiting Low Income Post-Partum Women into a Weight Loss Trial: In-Person versus Facebook Delivery

Tue, 05/16/2017 - 4:45pm

Several studies, such as the Diabetes Prevention Program (DPP), have provided foundational evidence for the effect of lifestyle modification interventions on diabetes prevention and weight loss. However, translating these programs to the real-world has proven difficult. There remains a need to increase the feasibility and reach of translational weight loss interventions.

PURPOSE: To compare the recruitment rates of overweight low income postpartum women into a DPP-adapted behavioral weight loss program delivered in-person versus delivered via Facebook.

METHODS: We compared two 8-week pilot behavioral weight loss trials; one delivered via weekly in-person group sessions and the other delivered entirely via Facebook. Both trials used the same recruitment methods: participants were overweight low income postpartum women within five Women Infants and Children (WIC) clinics in the Worcester, Massachusetts area recruited by nutritionists during routine WIC visits. Inclusion criteria included, childbirth in the previous 6 weeks to 6 months, age 18 or older, a body mass index (BMI) of > 27 kg/m2, and obstetric provider approval for participation in the diet and physical activity components of the intervention. Additional eligibility criteria for the Facebook intervention included: 1) ability to use the Internet daily; 2) having a Facebook account; 3) currently using Facebook at least once per week.

RESULTS: 27 and 54 women participated in the in-person and Facebook pilot trials, respectively. Among eligible women in the in-person trial, 62.1% gave permission to be contacted for the in-person trial, and 23.3% enrolled. Among eligible women in the Facebook trial, 59.7% of women agreed to be contacted, and 39.1% enrolled.

CONCLUSIONS: Recruitment rates for a Facebook-based weight loss intervention were higher than rates for an in-person intervention. Future efforts are needed to increase reach of weight loss interventions among overweight and obese low income diverse women.

Feasibility, Safety and Acceptability of Soy-Based Diet for Pregnant Women: Preliminary Results from a Pilot Randomized Controlled Trial

Tue, 05/16/2017 - 4:45pm

Background: Previous evidence suggests that soy containing foods may have beneficial effects on lipid and glycemic metabolism. Pregnancy is associated with a progressive deterioration in glucose and lipid metabolism, partially attributable to elevated estrogen concentrations. Little is known about the effects of soy intake on cardiometabolic risk factors in pregnant women.

Methods: A pilot RCT was conducted in 30 pregnant women who were randomized to receive counseling to consume a high-soy or low-soy foods containing diet. Assessments (physical measurements, food frequency questionnaires, fasting blood samples) were conducted at 14 and 28 weeks of pregnancy, and 6 weeks’ postpartum. Monthly follow-up calls were conducted to assess safety and encourage adherence.

Results: Both the high-soy and low-soy groups demonstrated high adherence (80-90%), defined as consuming soy foods ≥ 15 days in the past four weeks for high-soy group and ≤ 5 days for low-soy group. Five adverse events possibly associated with soy intake were reported (nausea, vomiting, diarrhea, itchy mouth); all were transient and resolved without sequelae. The high-soy group lost body fat between baseline and postpartum while the low-soy group gained body fat, as reflected by change in triceps skinfold thickness (-4.8 mm vs +3.6 mm, p=0.04). There was a trend towards an improvement in BMI in the high-soy group, both at 28 weeks (+1.4 vs. +3.6 kg/m2, p=0.15) and postpartum (-1.2 vs. +0.6 kg/m2, p=0.14). There were no differences between groups in fasting glucose, HDL-C, LDL-C, TG, or VLDL levels.

Conclusion: Initial results from this pilot RCT support the acceptability and safety of consuming soy-based whole foods during pregnancy. A larger-scale RCT is needed to further elucidate the effects of soy diet on cardiometabolic risk among pregnant women.

Development and Evaluation of a Mentorship to Hire Program for Facilitating Nursing Role Development and Transition to Practice

Tue, 05/16/2017 - 4:45pm

The purpose of this poster is to present an ongoing community engaged research (CER) initiative at the University of Massachusetts Dartmouth College of Nursing (CON) examining in what ways a mentorship to hire (MTH) program with community partners may facilitate role development and transition to practice for senior nursing students and retention in health care organizations upon graduation.

New nursing graduates have a difficult time transitioning to practice in part because of unrealistic perceptions about the nursing role. Difficult transitions can be costly to health care organizations (HCO) who often invest time and money in new graduate hires only for them to leave the practice setting after a short period of time. An additional concern is a current and anticipated shortage of nurses in specialty areas such as post-operative, emergency, and psychiatric nursing. As part of the CON curriculum, senior nursing students must complete 120 hours of mentorship in a health care organization during the last semester of their program where students are paired with a professional registered nurse in a one-on-one concentrated practicum. This practicum provides students with clinical experiences and facilitates transitions to practice, however, HCOs often have a limited number of nurses available for precepting our students in part because of an increased demand and competition between nursing schools for clinical placements.

In an effort to find a mutually beneficial solution, a mentorship to hire program was proposed and developed between two health care organizations and the CON. This poster will discuss the development of the CER program and plans for assessing transition to practice, perceptions of readiness for practice, role development, and retention of the new graduates upon completion of the program. Furthermore plans for evaluating health care organization perceptions including evaluation of fit for organizations, costs associated with training, and retention will also be presented.

Assessment of a Novel Pediatric Resident Simulation Curriculum

Tue, 05/16/2017 - 4:45pm

Aim: To assess the efficacy of a newly implemented resident simulation curriculum at a medium sized pediatric residency program.

Background: Many pediatric residency programs incorporate high-fidelity simulation into their curriculum, but there is limited data discussing the utility/educational impacts of a longitudinal/standardized/multimodal simulation curriculum. Several studies of simulation-based training have employed “self-efficacy” as a barometer for trainee education and performance 1,2,. The level of a person’s self-efficacy can influence their behavior and may be a pivotal factor in performance. We have implemented a newly devised standardized, multimodal resident simulation curriculum and used resident self-efficacy to assess its effectiveness.

Methods: Participants were UMass Pediatric and Med/Peds residents. Implementation of our curriculum occurred at the start of the 2016-2017 academic year. Surveys were administered to all residents prior to curriculum implementation and at 6 months post-implementation. They assessed resident self-efficacy with regards to specific technical/procedural skills (i.e. running a code, performing intubation, etc.) and resident confidence in their ability to identify/manage specific pediatric disease presentations (i.e. respiratory failure, tachyarrhythmia, etc.). Data was pooled and averaged for each resident class separately. We predetermined a 10% change in self-efficacy to be a clinically significant difference.

Results: 36 of 40 residents completed the initial survey and 31 completed the 6-month follow-up. PGY1 residents reported improved self-efficacy for 4 PALS-related skills and 8 pediatric case presentations. Similarly, PGY2 residents reported improved self-efficacy for 3 PALS-related skills and 6 pediatric case presentations. Conversely, PGY3/4 residents reported no significant change in self-efficacy for any survey question.

Conclusions: These results suggest that our newly implemented longitudinal, standardized, multidisciplinary, multi-modal simulation curriculum has significantly improved resident self-efficacy related to core Pediatric Advanced Life-Support (PALS) skills/topics, with the greatest impact affecting our PGY1 class. Further study and curriculum development will attempt to address this issue.

Defining Success in Perioperative Care Pathways for Hip Fracture Patients

Tue, 05/16/2017 - 4:45pm

PURPOSE: Hip fracture is an increasingly common cause of morbidity and mortality in the aging U.S. population. Multiple studies have shown that patients who undergo surgical repair within 48 hours of the initial injury have better outcomes. The use of a perioperative care pathway (PCP) for hip fracture patients combines prompt surgical repair with dedicated medical services tailored to patients’ specific comorbidities.

METHODS: Our level 1 trauma center implemented a PCP in October 2015, requiring only anesthesia (not hospital medicine) clearance prior to surgery. We identified all hip fracture patients who presented to our level 1 hospital for one year prior to, and one year following, implementation of the pathway. We then performed a comprehensive clinical chart review to collect demographic data, past medical history, and perioperative factors. We performed statistical analyses to evaluate whether using the pathway improved patient outcomes.

RESULTS: Preliminary analyses were performed on a series of patients pre- (n=96) and post-pathway (n=100). We summarized patient characteristics and reported these according to participation in the pathway. Distributions were evaluated for normality and to evaluate for outliers. Proportions were reported for categorical variables and assessed for differences using the chi-square test, and continuous data were summarized by means and standard deviations and assessed for differences using the t-test. We found that patients in the pathway worked with physical therapy (PT) an average of 16.8 hours earlier (p=0.013).

CONCLUSION: The use of PCPs represents an emerging approach to hip fracture management, but a widely generalizable PCP has yet to be definitively described. Our patients’ decrease in time to PT may be attributable to better postoperative optimization by hospitalist medicine. We anticipate that multivariate analyses will reveal additional gains. Ultimately, our experience may yield implications for the safe, cost- and time-effective surgical care of hip fracture patients nationally.

Liposomal Bupivacaine in Total Knee Arthroplasty: Preliminary Results of a Two-Surgeon, Retrospective Study

Tue, 05/16/2017 - 4:45pm

INTRODUCTION: Liposomal bupivacaine (LB) is a slowly degrading preparation that provides local anesthesia for up to 72 hours. It targets the site directly responsible for pain sensation, with no associated motor blockade. In total knee arthroplasty (TKA), it may have superior outcomes to anesthesia with regional nerve block.

METHODS: Our surgeons began using LB in TKA patients in 2013. All patients following each surgeon’s LB start date were the experimental group. An equivalent number of patients prior to 2013 served as the control group. All control group patients received a preoperative femoral nerve block, and all experimental group patients received peri- and intra-articular LB, delivered intraoperatively. All other surgical and anesthesia interventions were the same. We used retrospective chart review to identify patient demographics, time to first ambulation, time to discharge, and incidence of postoperative nausea and vomiting. We also recorded opioid consumption intraoperatively, in the recovery room, and on the floor.

RESULTS: There were 161 patients in each group. We found no significant difference between the two groups with regard to gender, age, weight, preoperative opioid exposure, side of procedure, type of anesthesia (general vs. spinal), or ASA status. On average, LB patients consumed 29.2% less opioid after leaving the recovery room (p

DISCUSSION AND CONCLUSION: With increasing focus on the cost of TKA, there is strong incentive to manage costs associated with the procedure. Additionally, all patients, regardless of comorbid conditions, can benefit from limited exposure to narcotic pain medication. Our results indicate that LB decreases total systemic opioid requirement, time to first ambulation, and time to discharge from the hospital.

Combined Active Humoral and Cellular Immunization Approaches for the Treatment of Synucleonopathies

Tue, 05/16/2017 - 4:45pm

Objectives: Parkinson’s Disease (PD), Dementia with Lewy bodies (DLB), and Multiple System Atrophy (MSA) are neurodegenerative disorders of the aging population characterized by the progressive accumulation of alpha-synuclein. Jointly these disorders have been denominated synucleinopathies and currently no disease modifying treatments are available. Previous in vivo studies in transgenic (tg) mice have shown that active and passive immunization targeting alpha-synuclein ameliorates to some extent deficits and synuclein accumulation, however it’s unknown if combining humoral and cellular immunization might synergize and also reduce inflammation and improve microglial cell mediated synuclein clearance.

Methods: PDGF- alpha-synuclein tg mice and control non-tg mice were immunized with: 1) Glucan Particle (GP) adjuvant alone, 2) GP human (hu)- alpha-synuclein (active immunization), 3) GP plus rapamycin and 4) GP plus rapamycin and hu-alpha-synuclein (combined active and humoral) and analyzed by neuropathological and biochemical markers.

Results: Compared to tg mice treated with adjuvant alone, mice immunized with GP hu-alpha-synuclein displayed a 30% reduction in alpha-synuclein accumulation. Combined immunotherapy with GP plus rapamycin and hu-alpha-synuclein resulted in 50% reduction in alpha-synuclein accumulation which was accompanied by reduced neuro-inflammation (Iba-1, GFAP, IL6, TNFalpha), phospho and insoluble alpha-synuclein, microglia and astroglia cell numbers, and retention of CD25, FoxP3 and CD4 positive cells. Levels of TGFb1 were also increased. Serological studies showed that active immunization resulted in higher levels of total IgG, IgG1 and IgG2 titers, levels were slightly higher in the combined group.

Conclusions: In vivo studies targeting alpha-synuclein support the hypothesis that cellular immunization might enhance the effects of active immunotherapy for the treatment of synucleionopathies.