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Emergency Medicine Providers Systematically Underestimate Their Opioid Prescribing Practices

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

Background: Opioid misuse is a known public health problem, nationwide and in Massachusetts. The Massachusetts Hospital Association (MHA) developed recommendations to address opioid prescribing in the ED setting, and UMassMemorial Health Care recently implemented a system-wide opioid practice guideline mirroring the MHA policy. Little is known about methods to influence behavior change among ED providers related to opioid prescribing practices. Guideline implementation provided a unique opportunity for a natural experiment related to prescribing patterns, and we hypothesized that a simultaneous experimental intervention to provide clinicians with their individual prescribing data would alter their practices beyond any effect achieved solely by being subject to the new guidelines.

Methods: As part of an ongoing, prospective, randomized trial of an intervention hypothesized to influence providers’ opioid prescribing, we developed a survey instrument consisting of graphical depictions of the distributions of three measures of opioid prescribing among all ED providers at four UMass-affiliated EDs (attending and resident physicians and advanced practice providers). Clinicians randomized to the intervention arm were asked to identify his/her perceived position on each distribution. We compared each provider’s self-perception to their actual decile.

Results: Fifty-one providers were randomized to the intervention arm. Forty-eight completed the survey (94%). Providers underestimated their decile of opioid prescriptions per hundred total prescriptions by a median of one decile (p=0.0399 for difference from zero). Attendings underestimated their decile of percentage of patients dispositioned with an opioid prescription by a median of two deciles (p=0.0292), while residents did not exhibit a significant difference. Providers showed systematic disagreement with their raw number of prescriptions for extended-release opioid formulations (kappa -0.18), underestimating by a median of one.

Conclusions: Based upon three measures of ED opioid prescribing, providers’ self-perceptions of their practices systematically underestimated their actual prescribing, which likely has implications related to efforts to influence clinician behavior change.

Correlates of hyaluronic acid and corticosteroid injections among patients with radiographically confirmed osteoarthritis

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

Objective: Despite the rapid proliferation of hyaluronate (HA) and corticosteroid (CO) injections and clinical guidelines regarding their use in osteoarthritis (OA), information on the characteristics of people receiving them is scarce. We described use of injections among adults with radiographically confirmed knee OA and identified correlates of injection use.

Methods: We used publicly available data from Osteoarthritis Initiative and included participants with ≥ one radiographically confirmed knee OA (Kellgren-Lawrence grade (K-L) > 2) at baseline. We matched 415 participants reporting HA and/or CO during the 6 month before one of the first 7 annual follow-up assessments to 1,841 non-injection users by randomly selecting a study visit to match the distribution observed in the injection users. Multinomial logistic regression models identified correlates of injection use including sociodemographics and clinical/functional factors.

Results: Injections were common (16.9% -year 1, 13.7% -year 2, 16.6 % -year 3, 13.5% - year 4, 15.9% -year 5, 13.5 % -year 6 and 9.9% -year 7) with corticosteroid injections most common (68.4%). HA and CO were more commonly reported by those with higher income (e.g. adjusted Odds Ratio (aOR) HA > $50k versus < $25k: 3.63; (95% CI: 1.20-10.99)) and less common among blacks (aOR HA: 0.19; 95% CI: 0.06-0.55). Greater K-L grade (grade 4 versus 2) was associated with increased odds of HA (aOR: 4.79; 95% CI: 2.47-9.30), CO (aOR: 1.56; 95% CI: 1.04-2.34), or both (aOR: 4.94; 95% CI: 1.99-12.27).

Conclusion: Hyaluronic acid or corticosteroid injections are associated with higher socioeconomic positioning and indicators of greater disease severity.

Using Interviews to Understand Patients’ Post-operative Pain Management Educational Needs Before and After Elective Total Joint Replacement Surgery

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

Objective: To better understand the education needs of patients electing to have TJR in managing their pain in the post-operative period after discharge from the hospital.

Methods: An exploratory, descriptive, qualitative design. Convenience sample of people who reported that they had not received information about pain management prior to TJR surgery were recruited from 9 surgeon practices in 8 states to participate in telephone interviews, utilizing open-ended questions. Questions included: recollection of pre-op class attended and content; experiences with surgical pain after surgery and how it was managed; experiences with pain medicine; experience using non-medicine related pain reduction methods; suggestions for delivery of pain management information. Interviews were recorded and transcribed. Data were categorized using content analysis techniques.

Results: Seventeen patients were interviewed. Although all remembered attending a pre-operative class prior to their joint replacement surgery, none remembered receiving information during that class about managing pain once they were discharged. All had been prescribed an opioid for pain management post-operatively; however no patients reported receiving any information regarding use of the medication other than the information on the pill bottle. Many had concerns regarding the use of opioids to control their pain, including side effects, such as constipation and the risk of addiction. The most common non-medicine method used to manage pain was the use of ice. Participants believed that information about pain management, including both non-medicine approaches and instructions for taking opioids would be helpful and should be delivered at multiple time points, including pre-operatively, at discharge, and within the first few days after discharge.

Conclusion: With trends toward shorter hospital stays, home based pain management is a priority. Understanding the pain management education needs of patients considering elective TJR could inform interventions for this population as well as provide insight into the needs of other patients undergoing surgery.

Effective Pain Information Pre-operatively is Associated with Improved Functional Gain after Total Joint Replacement

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

Objective: We evaluated receipt of pre-operative pain management education in a national prospective cohort on post-operative pain and function.

Methods: Preoperative, 2 week and 6 month postoperative data from a nationally representative cohort of 1404 primary unilateral TJR patients with a date of surgery between May 2011 and December 2014. Data included demographics, comorbid conditions, operative joint pain severity (HOOS/KOOS), musculoskeletal disease burden, physical function (SF36 PCS), and mental health (SF36 MCS). At 2 weeks post-op, patients were asked if they had received information prior to surgery about pain management options and if so, how helpful the information was. Additionally, patients were asked about use of non-medication methods to relieve operative joint pain. Descriptive statistics were performed.

Results: One third reported not receiving information about pain management; an additional 11% did not find it helpful. There were no differences pre-operatively in demographics, comorbid conditions, operative joint pain severity, musculoskeletal disease burden, SF36 PCS and MCS between those who received information and those who did not. Patients who received information about pain management options were more likely to use non-medication methods to relieve operative joint pain (p< 0.000). They reported less current pain (p = 0.02) and maximum pain (p = 0.03) in their operative joint at 2 weeks post-op. At 6 months post-op, patients who reported not receiving information about pain management had statistically lower physical function scores that those receiving information (p = 0.04). There was no difference in HOOS/KOOS pain scores 6 months post-op.

Conclusion: More than 40% of TJR patients in this study reported that they did not receive or received unhelpful information regarding post-op pain management options, highlighting a need for more consistent patient education. In this study, the lack of pain management information appears to negatively impact 6 month post-operative function.

Does the Indication for Breast Surgery Impact Surgical Outcomes? A Contemporary Analysis of the ACS-NSQIP Database

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

Background. There is limited data about whether perioperative outcomes differ based on the indication for breast surgery. Herein we aim to assess if breast surgery for prophylaxis, compared to that for malignancy, impacts surgical outcomes.

Methods. All women who underwent simple or subcutaneous mastectomy were identified from the 2007-2012 ACS-NSQIP database. Patients were identified by their ICD-9 codes and categorized into two groups. Group 1 consisted of patients diagnosed with breast cancer or carcinoma in situ; group 2 consisted of patients diagnosed with a genetic predisposition to malignant neoplasm of the breast (i.e., BRCA mutation). Demographic and preoperative variables were compared between groups and outcome variables. Outcome variables were analyzed using age- and operative time-adjusted logistic regression models.

Results. 30,803 patients were identified. Group 1 consisted of 30,644 (99.5%) patients diagnosed with malignancy; group 2 consisted of 159 (0.5%) who underwent prophylactic surgery. In univariate analyses, those undergoing prophylactic surgery were significantly younger (p < 0.01). There were no other preoperative differences between groups. When adjusted, the prophylactic group demonstrated a greater risk of DVT (p = 0.03). There were no differences in mortality, superficial/deep/organ space infections, UTI, wound dehiscence, or MI.

Conclusion. In this analysis of a national cohort of breast surgery patients, those undergoing prophylactic surgery due to a genetic predisposition had a greater risk of perioperative DVT, compared to those who underwent surgery for a diagnosis of malignancy. This data may allow for improved perioperative management of patients to prevent DVT development and their devastating consequences.

Synthetic intestinal mucosal barrier using a hydrogel slab integrated microfluidic chip

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

The mucosal barrier lining along the intestinal tract plays a key role in metabolic and immunological homeostasis. Repeated disruption of the mucosal barrier integrity has been suggested to be a precursor event that derives inflammatory bowel diseases and colorectal cancer. Multiple in vitro platform technologies have been developed to understand the mucosal barrier function including trans-wells and microfabricated devices, but a static and vertical axis culture settings limits to simulate and observe dynamic complexity of the gut microenvironment. Here, we introduce a biomaterials engineering approach to create a synthetic mucosal barrier in a transverse manner for direct observation of cellular processes. A type I collagen hybridized polyacrylamide hydrogel supporting small molecular transport and epithelial cell adhesion was used as a framework and subsequently anchored covalently to a glass slide via silanization chemistry. Villous microstructures ~250µm in height were manufactured by casting the hydrogel precursor solution in a pre-designed, removable polydimethylsiloxane micropattern mold and polymerizing using UV light. After sealing the device with another glass slide, we increased the cellular and extracellular complexity of this microfluidic chip by sequentially introducing (i) HT-29 colon epithelial cells, (ii) mucin extracts from a pig intestine, (iii) bacteria, and (iv) human peripheral blood-derived mononuclear cells and co-cultured them in a single device. This modular in vitro microphysiological intestinal tissue model may serve as a translational platform to discover the biophysical etiology for disruption of the mucosal barrier and associated inflammatory diseases.

Estimated and self-reported workloads and lower extremity symptoms for nurses and nursing assistants

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

Objectives and Significance: In US nursing homes, nursing assistants (NAs) are responsible for direct care and resident handling, while nurses’ roles consist primarily of medication distribution and administrative duties. This study examines differences in observed physical exposures and self-reported knee and ankle symptoms of nurses and NAs.

Methods: Observations of clinical staff’s postures and handling were made at fixed time intervals using the PATH Method. An additive physical workload index (PWI) was computed to compare LE workload of NAs and nurses. The PWI combined observed frequencies of postures and handling with their associated forces on the knee and ankle derived from the University of Michigan’s 3D Static Strength Prediction Program. Additionally, surveys on health and working conditions were distributed to employees at 24 nursing homes. Knee and ankle symptoms in the past three months and physical demands were examined by clinical job.

Results: Frequencies of postures and handling input into the PWI were based on observations of 275 NAs and 40 nurses. The analysis of PWI for the LE demonstrated higher physical exposures on both the knee and ankle for NAs compared to nurses, especially while NAs were performing resident handling. Among survey participants (n = 1467), NAs reported higher mean physical exertion scores than nurses and also higher frequencies of knee and ankle symptoms (p=0.0076) in the previous three months.

Conclusions: In this study, both estimated and self-reported physical workloads were higher among NAs compared to nurses. LE symptoms were also more common among NAs. Safe handling equipment helps reduce some LE exposures for NAs, but interventions for other strenuous tasks should be considered to reduce LE pain symptoms, such as introducing lighter food carts often pushed by NAs and limiting the number of dirty linens bagged before transporting to the soiled linen drop-off.

Health Applications of Social Network Analysis and Computational Social Science

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

Social network analysis has proliferated across the social and behavioral sciences, shifting our analytical focus from individuals to the patterns of social ties that connect them. This perspective has enriched our understanding of a great variety of health-related phenomena, including the spread of STDs on contact networks, the spread of health care practices on physicians’ professional networks, the dynamics of patient transfers on networks of clinics, and the spread of weight-related behaviors among adolescents at risk for obesity. The advent of the era of computational social science has augmented the contributions of this perspective, by moving beyond expensive and laborious methods of questionnaires and direct observation to incorporate new techniques of data collection and analysis. For example, these include analysis of electronic health records or other time-stamped communication traces among healthcare practitioners; streams of behavioral data from wearable sensors, location-aware devices, or electronic calendars; automated analysis of text in documents; and mapping networks of interaction by citations and collaboration in clinical research literatures. Whereas much of computational social science has offered new ways of monitoring health behavior and healthcare behavior, or for analyzing those data, a further contribution has been to directly analyze these social processes in system dynamics models, microsimulation, and agent-based models. These approaches allow for computational experiments that assist in predicting and interpreting outcomes from health interventions. This poster will highlight some of my recent and pending work in this domain, aiming to identify potential collaborators in UMCCTS for projects that involve social networks or computational social science.

A Pilot Randomized Controlled Trial of a Videoconferencing Smoking Cessation Intervention for Korean American Women: Preliminary Findings

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

Introduction: Korean American women prefer online or telephone smoking cessation interventions that can be remotely accessed from home. However, these interventions have been found ineffective for the group.

Methods: This study is a pilot clinical trial testing the feasibility and acceptability of a videoconferencing smoking cessation intervention for Korean American women and compared its preliminary efficacy with a telephone-based smoking cessation intervention. Korean women in the United States were recruited nationwide and randomly assigned at a ratio of 1:1 to either a video arm or a telephone arm. Participants in both arms received eight 30-minute weekly individualized counseling sessions of a culturally adapted smoking cessation intervention and nicotine patches for 8 weeks. They were followed up at post-quit 1, 2, and 3 months.

Results: A total of 168 Korean Americans were assessed for eligibility, 77 were determined to eligible and 49 participated in the study. The videoconferencing intervention was acceptable and feasible for women under 50 years, whereas it was not for older women. The videoconferencing intervention produced abstinence rates of 67% at post-quit 1 month and 42% at post-quit 3 months based on self-report. The rate at post-quit 3 months dropped to 33% when those women whose abstinence could not be validated with salivary cotinine tests were treated as smoking. Abstinence rates in the telephone arm did not differ from those in the video arm.

Conclusion: Findings suggest that videoconferencing smoking cessation intervention may be feasible and acceptable for Korean American women under 50 years. However, for older Korean American women, the intervention may not be feasible and telephone-based intervention seems to be just as effective if smoking cessation intervention components are adapted at a deep structural level of Korean culture by integrating its core cultural values and addressing psychosocial, social and environmental forces affecting the behavior.

Long-lasting Effects of Perinatal Exposure to Brominated Flame Retardant on Male Reproductive Outcomes in Rat Model

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

Meta-analysis of 101 studies published between 1934 and 1996 indicates that mean sperm concentration decreased around 50% during this period. More recent studies have found alarmingly poor semen quality in the general population of Northern Europe. Additional adverse trends include increased incidence of testicular cancer, and congenital malformations such as cryptorchidism and hypospadias. Testicular germ cell cancers increased by about 400% over the period of 50 years in industrialized countries. Decreased quality of male reproductive health has been linked to environmental endocrine disruptors exposure. However, the ability of xenobiotics to produce long-lasting effects and mechanisms of perturbation of the male reproductive system following developmental exposures are not well understood. Both animal experiments and human studies show male reproductive toxicity to polybrominated diphenyl ethers (PBDE), a group of ubiquitous, persistent, and bioaccumulative environmental xenobiotics. Here we report the result of experiment in which pregnant Wistar rats were fed 0.2 mg/kg body weight BDE-47 (the most ubiquitous PBDE congener) daily starting from the eighth day of pregnancy until weaning. Multiple endpoints of male reproductive health were assessed in offspring on postnatal week 20: testis size, sperm production, morphology, motility, circulating testosterone, select gene expression in prostate (qRT-PCR) and all-genome gene expression in testis (RNA-seq). Seventeen weeks after exposure was abolished testis size was significantly smaller in adult rats and genes of inflammatory response were significantly upregulated in testis tissue among other results. Our findings confirm male-reproductive toxicity of PBDE and identify inflammatory response as a long lasting mechanism of repro-toxicity triggered by perinatal exposure.

Characterization of Respiratory Phenotype in Very Long-chain Acyl-CoA Dehydrogenase Deficient Mice.

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

Rationale: Very Long-chain Acyl-CoA dehydrogenase (VLCAD) deficiency the most common inherited long-chain fatty acid disorder. The VLCAD enzyme catalyzes the first step of mitochondrial fatty acid oxidation and loss of the enzyme results in energy deficiency as well as accumulation of long chain fatty acids. Recently, a related enzyme, Long-chain Acyl-CoA dehydrogensase (LCAD), which unlike VLCAD is not highly expressed in metabolic tissues like liver, heart and skeletal muscle, was found to be expressed in the lung and surfactant and lung dysfunction were observed in LCAD deficient mice. Respiratory distress syndrome has been described in other fatty acid oxidation disorders. VLCAD is expressed in lung, and likely plays an important role in lung compliance.

Methods: VLCAD deficient mice and litter-mate controls were fasted for 18 hours, then exercised on a treadmill for 2 hours. Breathing was immediately assessed using whole body plethysmography in unanaesthetized spontaneously breathing mice. After a stable baseline was achieved, mice were given a “respiratory” challenge with 7% hypercapnia. In a subgroup of animals, pulmonary mechanics were assessed using Flexivent (Scireq).

Results: Following exercise, VLCAD deficient mice had a decreased tidal volume and minute ventilation compared to their wild type controls. However, post-exercise VLCAD deficient mice were able to stabilize to similar levels as wild-type during baseline. The VLCAD deficient mice had a decreased response to a respiratory challenge with 7% hypercapnia. Early preliminary results suggest that VLCAD deficient animals have lower airway resistance.

Conclusions: Respiratory insufficiency was demonstrated in a fasted and exercise challenged VLCAD deficient mice.

Neighborhood Differences in the Availability of Healthy Foods in the City of Worcester

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

INTRODUCTION. Neighborhood food environment is important to healthy eating. The availability and proximity of healthy foods has been shown to affect dietary quality, obesity, and overall health. We surveyed food stores throughout City of Worcester to assess the variability of food availability in neighborhoods and inequalities in access to fresh produce, unprocessed foods, and other healthy food options by neighborhood socioeconomic status (N-SES).

METHODS. Where permitted by the store manager, the Community Nutrition Environment Evaluation Data Systems (C-NEEDS) survey was completed inside the store by trained staff. Healthy Food Availability Index (HFAI; range 0-56) and Unhealthy Food Availability Index (UFAI; range 0-39) were calculated for each store. Higher HFAI indicates higher availability of healthy food items, and higher UFAI indicates high availability of unhealthy foods. Median household income and car ownership data were derived at the census tract level as measures of N-SES using the 2013 US Census American Community Surveys 5-Year estimates.

RESULTS. Convenience stores (mean HFAI 7.9, UFAI 21.1) had lower availability of both healthy and unhealthy foods than grocery stores (HFAI 32.4, UFAI 29.8). However, convenience stores had a higher proportion of unhealthy foods to healthy foods. Neighborhoods with lower median income and car ownership had a greater density of convenience stores. Neighborhoods with higher SES and car ownership had less access to convenience stores. Grocery stores in higher SES neighborhoods had more healthy food options.

DISCUSSION. These results demonstrate that residents in lower SES neighborhoods may be disadvantaged when it comes to availability of healthy foods. These neighborhoods have higher density of convenience stores that may promote an unhealthy eating environment. Residents in these neighborhoods may wish to make healthy choices, but without access to a car may be unable or unwilling to walk to the nearest store where healthy alternatives are available.

Towards Pharmacovigilance Using Machine Learning To Identify Unknown Adverse Reactions Triggered By Drug-Drug Interaction

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

Adverse Drug Reactions (ADRs) are a major cause of morbidity and mortality in world. There is thus a growing need of methods facilitating the automated detection of drugs-related ADR; especially ADRs that were not known from clinical trials but later arise due to drug-drug interactions. In this research our goal is to discover the severe unknown Adverse Drug Reactions caused by a combination of drugs, also known as Drug-Drug-Interaction. We propose to use Association Rule Mining to find the ADRs caused by using a combination of drugs yet not known to be caused if these drugs were taken individually. For evaluation, we will test out the proposed strategies on real-world medical data extracted from the spontaneous adverse drug reaction reporting system called FAERS. The results mined by our tool will be checked both manually by literature review and then verified by domain experts for interestingness and accuracy.

Reducing Phlebotomy-­Induced Blood Loss in the PICU: A Quality Improvement Study

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

Introduction: Phlebotomy­induced blood loss contributes to development of anemia in critically ill children. Major factors contributing to this include blood overdraw from indwelling catheters and utilization of larger volume containers. We targeted these causes of excessive blood draws to decrease volumes of both the discarded blood and sample sent to the laboratory for standard tests. Methods: Pre and post quality improvement study in a 10­bed pediatric intensive care unit 2014­2015. All patients admitted to PICU during each 2­month study period were eligible for enrollment. Pre-intervention, nurses used standard pediatric tubes (3­3.5mL). A wash­out period followed. For intervention, email survey and nursing/resident education sessions were used to standardize discard volumes and introduce microtainers (500µL) for standard hematology, chemistry, and coagulation tests. All blood draws were recorded. Incomplete tests due to lack of volume or clotting were recorded. Results: 45 patients (138 blood draws) in pre­intervention phase and 32 patients (142 draws) in intervention phase were enrolled. Pre­intervention, mean total blood volume sent to the lab was 2.25 ±1.87mL and mean discard volume was 1.64 ±1.67mL. Post­intervention, mean total volume of blood sent and mean discard volume were significantly reduced, 1.52 ±1.50mL, p<0.05, and 0.89 ±0.61mL, p<0.05, demonstrating 32.4% and 45.7% reductions in blood volume respectively. There was no change in test failures due to low volume or clotting. Samples from peripheral intravenous catheters comprised the majority of the cohort. Pre­intervention, mean total blood volume from PIVs (n=116) was 2.06 ±1.51mL, and mean discard volume was 1.74 ±1.33mL. Post­ intervention (n=72), mean total volumes significantly decreased to 1.39 ±1.49mL and 1.15 ±0.53mL respectively (p<0.05). Conclusions: We demonstrated a significant reduction in phlebotomy­induced blood loss by standardizing discard volumes and using microtainers to avoid sending unnecessary blood volumes to the lab.

Translating dosage compensation to trisomy 21

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

Down syndrome is the leading genetic cause of intellectual disabilities, occurring in 1 out of 700 live births. Given that Down syndrome is caused by an extra copy of chromosome 21 that involves over-expression of 400 genes across a whole chromosome, it precludes any possibility of a genetic therapy. Our lab has long studied the natural dosage compensation mechanism for X chromosome inactivation. To “dosage compensate” X-linked genes between females and males, the X-linked XIST gene produces a large non-coding RNA that silences one of the two X chromosomes in female cells. The initial motivation of this study was to translate the natural mechanisms of X chromosome inactivation into chromosome therapy for Down syndrome. Using genome editing with zinc finger nucleases, we have successfully inserted a large XIST transgene into Chromosome 21 in Down syndrome iPS cells, which results in chromosome-wide transcriptional silencing of the extra Chromosome 21. Remarkably, deficits in proliferation and neural growth are rapidly reversed upon silencing one chromosome 21. Successful trisomy silencing in vitro surmounts the major first step towards potential development of “chromosome therapy” for Down syndrome. The human iPSC-based trisomy correction system we established opens a unique opportunity to identify therapeutic targets and study transplantation therapies for Down syndrome.

Which is the primary factor influencing running stride parameters: age or lower limb strength?

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

Much still remains unknown about the impact of age, and age-related changes in muscle function, on gait parameters. The aim of this study was to examine the impact of strength on running gait parameters across the adult lifespan. We tested the hypothesis that a greater amount of the variance in peak hip, knee and ankle sagittal plane moments would be explained by peak isometric joint torques as compared to age. Twenty-four healthy adults, ages 20-66 years, completed 5 trials on an overground 20-meter runway at a standardized velocity of 3.5 ms-1 (± 5%). Participants performed maximal isometric plantar flexion and knee extension for three contractions lasting three seconds each. Linear regression analysis between strength, age, and moments were performed. At the ankle, age alone explained 14.4% of the variance in the peak ankle joint moment. There was not a significant increase in the variance explained when strength was added to the model. At the knee, neither age nor strength explained a significant portion of the variance in peak knee moments. However, together age and strength explained 27.9% of the variance in the peak knee moment. No significant associations were found between the hip moments and either knee and ankle strength. These results suggest that other age-related physiological changes may drive changes in gait mechanics more so than maximal torque production. A more dynamic measure of muscle function, such as power or isokinetic torque at varying speeds may have greater predictive value for gait performance.

Remotely Triggered Polymeric Nanoparticles for the Treatment of Triple Negative Breast Cancer

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

Triple Negative Breast Cancer (TNBC) has the worst prognosis among all the sub-types of breast cancer. Currently no targeted treatment has been approved for TNBC management. While TNBC does not overexpress hormone receptors, it has been found to over express certain receptors like transferrin (TfR) or folate receptors. The aim of this research is to synthesize targeted polymeric nanoparticles for TNBC. MDA-MB-231 cells are used as a representative TNBC cell line in this study. Active targeting of TNBC is achieved by conjugating the nanoparticles to a peptide (Tr) that binds to the TfR. Photodynamic Therapy (PDT) using polymeric nanoparticles was explored for TNBC treatment. PDT utilizes a secondary form of targeting by remotely triggering benzoporphyrin derivative monoacid (BPD) using near infrared light. When irradiated at 690nm, BPD induces cytotoxicity via generation of reactive oxygen species. The polymeric nanoparticles were characterized for size, zeta potential, and drug release at 37°C. The morphology of the nanoparticles was confirmed using electron microscopy and cell uptake was monitored in vitro using fluorescent microscopy. PDT was carried out at 500nM BPD concentration using a 690nm laser. Cytotoxicity of these targeted polymeric nanoparticles was assessed using a standard colorimetric viability assay (MTT). The nanoparticles synthesized were fairly monodisperse and the release studies demonstrated sustained BPD release from the nanoparticles. Receptor mediated endocytosis of the active nanoparticles was studied by using FITC conjugated peptide and the FITC signal was observed using fluorescent microscopy. Stronger BPD fluorescent signal for the active targeting nanoparticles (PLGA-PEG-Tr) compared to the passive (PLGA-PEG) nanoparticles. Significant cell death following PDT was observed in all the treatment groups, which was also confirmed by imaging the cells post-treatment using standard live-dead stain. PDT is a fairly versatile and non-invasive form of treatment and using targeted nanoparticles it can be adapted for other drugs and diseases.

Hospice and pain management in nursing home residents with cancer

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

Background: The prevalence of untreated pain in nursing home residents with cancer is unacceptably high. Hospice may increase the likelihood of receiving pain management at the end of life.

Objectives: To estimate whether receipt of hospice in nursing homes increases the receipt of pain management for nursing home residents with cancer at the end of life.

Methods: We conducted a cross-sectional study on a national sample of Medicare decedents who had cancer and were nursing home residents during the last 90 days of life in 2011–2012. We used the last Minimum Data Set (MDS) 3.0 assessment before death and the Medicare Beneficiary Summary File to measure hospice use, pain, and pain management at the last MDS assessment. We matched residents with cancer and in pain who received hospice care to residents in pain not receiving hospice care on nursing home facility and time from last MDS assessment to death. The primary outcomes were receipt of pharmacologic pain management including scheduled and PRN analgesics and non-pharmacologic pain management. Conditional logistic models were used to estimate the association between hospice use and pain management.

Results: In matched analyses, untreated pain was uncommon (2.9% in hospice users and 5.6 in non-hospice users), though there was an absolute difference of 15.4% in scheduled analgesics use between hospice and non-hospice users (71.5% vs. 56.1%, respectively). Hospice use was associated with receipt of scheduled analgesics (adjusted Odds Ratio(aOR): 1.85, 95% Confidence Interval(CI):1.73–1.97), PRN medication (aOR: 1.31, 95% CI:1.20–1.43), and non-pharmacologic pain management (aOR: 1.18, 95% CI:1.11–1.26).

Conclusions: Untreated pain at the end of life among nursing home residents with cancer was unusual. Hospice use was associated with increased pain management in nursing home residents with documented pain. Further work to examine the type and effectiveness of pain management strategies used is warranted.

Crystal protein Cry5B as a novel and powerful anthelmintic

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

Soil-transmitted helminths (STHs), most notably, hookworms, whipworms, and Ascaris, are nematodes that infect more than 1.5 billion of the poorest people and are amongst the leading causes of morbidity worldwide. Only two classes of de-worming drugs (anthelmintics) are available for treatment, and only one is commonly used in mass drug administrations. New anthelmintics are urgently needed to overcome emerging resistance and to produce higher cure rates. Crystal (Cry) proteins, in particular Cry5B, made by Bacillus thuringiensis (Bt) are promising new candidates. Cry5B has excellent anthelmintic properties against many free-living and parasitic nematodes, including in vivo efficacy against multiple STH infections in rodents (Heligomasmidoes polygyrus and Ancylostoma ceylanicum) and in pigs (Ascaris suum).

An enormous challenge for STHs, very different from most diseases worked on in the developing world, is the requirement that therapies be very cheap (the people infected are very poor and current drugs costs pennies a dose), massively scalable (over 4 billion people are at risk from infection), and have a long shelf life in harsh environments, that have high temperature and humidity and no cold chain.

We will update our progress in several key areas. We will present new data on the in vivo activity of Cry5B against a major human parasite in humans. We will also present data on the whether or not the immune system is required for Cry5B action in vivo. We will also present on our development efforts to produce a deployable version of Cry5B that is cheap, safe, scalable, and stable. These efforts are currently focused on bacterial engineering, expression, and formulation.

Theoretical and Experimental Analysis of the Antioxidant and Anti-amyloid Features of Synthetic Resveratrol Mimics

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

Diaryl hydrazones, possessing similar structure to the popular red wine antioxidant resveratrol, have been previously identified as multitarget compounds interfering with several processes associated with the pathogenesis of Alzheimer’s disease (AD). These compounds exhibited particularly strong inhibition of the amyloid beta (A) peptide self-assembly, including blocking the formation of fibrils and oligomers, species that are widely accepted to be neurotoxic. The molecules were also powerful free radical scavengers and thus have a potential to defend against oxidative stress.

In order to learn more about the mode of action of the compounds, theoretical and experimental studies have been carried out. First, the structural, energetic and electronic features of the core structure have been elucidated by density funtional theory (DFT) calculations. The DFT results identified the most likely form of the compounds, which was applied to a broad range of calculations using substituted derivates. Based on the structural information several characteristics such as logP, H-binding energy, HOMO-LUMO energies and band gap and electron densities were calculated. The compounds were subjected to three different antioxidant assays (DPPH, ABTS and ORAC). The % radical scavenging has been analyzed as a function of the above determined structural parameters in order to identify the role of the energetic and electronic features in the antioxidant activity. The analysis of the same parameters as potential markers to the anti-amyloid activity has also been carried out.

Isotope labeling via H-D exchange and in situ hydrazone-radicals as well as hydrazone-A complex formation, applying 1H-NMR and HRMS, have also been used to experimentally observe the potential role of various tautomeric forms and the partially delocalized electron structure of the hydrazones.