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2016 UMCCTS Research Retreat Poster Session

Thu, 10/13/2016 - 7:05pm

Poster Session at 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.

Vasan S. Ramachandran, MD at 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:05pm

Keynote speaker, Vasan S. Ramachandran, MD, FACC, at 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.

Vasan S. Ramachandran, MD at 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:05pm

Keynote speaker, Vasan S. Ramachandran, MD, FACC, at 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.

Vasan S. Ramachandran, MD at 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:05pm

Keynote speaker, Vasan S. Ramachandran, MD, FACC, at 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.

Students at 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:05pm

Students at 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.

Students at 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:05pm

Students at 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.

Characterizing the trajectories of vasomotor symptoms across the menopausal transition

Tue, 10/11/2016 - 3:45pm

OBJECTIVE: The aim of the study was to investigate the heterogeneity of temporal patterns of vasomotor symptoms (VMS) over the menopausal transition and identify factors associated with these patterns in a diverse sample of women.

METHODS: The Study of Women's Health Across the Nation is a multisite longitudinal study of women from five racial/ethnic groups transitioning through the menopause. The analytic sample included 1,455 women with nonsurgical menopause and a median follow-up of 15.4 years. Temporal patterns of VMS and associations with serum estradiol and follicle-stimulating hormone, race/ethnicity, body mass index, and demographic and psychosocial factors were examined using group-based trajectory modeling.

RESULTS: Four distinct trajectories of VMS were found: onset early (11 years before the final menstrual period) with decline after menopause (early onset, 18.4%), onset near the final menstrual period with later decline (late onset, 29.0%), onset early with persistently high frequency (high, 25.6%), and persistently low frequency (low, 27.0%). Relative to women with persistently low frequency of VMS, women with persistently high and early onset VMS had a more adverse psychosocial and health profile. Black women were overrepresented in the late onset and high VMS subgroups relative to white women. Obese women were underrepresented in the late onset subgroup. In multivariable models, the pattern of estradiol over the menopause was significantly associated with the VMS trajectory.

CONCLUSIONS: These data distinctly demonstrate heterogeneous patterns of menopausal symptoms that are associated with race/ethnicity, reproductive hormones, premenopause body mass index, and psychosocial characteristics. Early targeted intervention may have a meaningful impact on long-term VMS.

Screening for Post-traumatic Stress Disorder in Prenatal Care: Prevalence and Characteristics in a Low-Income Population

Tue, 10/11/2016 - 3:45pm

Objectives: Investigate the feasibility of using a brief, 4-item PTSD screening tool (PTSD-PC) as part of routine prenatal care in two community health care settings serving ethnically and linguistically diverse low-income populations. Report prevalence and differences by sub-threshold and clinical levels, in demographic, health, mental health, risk behaviors, and service use.

Methods: Women were screened as part of their prenatal intake visit over a 2-year period. Those screening positive at clinical or sub-threshold levels were recruited if they spoke English, Spanish, Portuguese, Vietnamese or Arabic. Enrolled women were interviewed about psychosocial risk factors, prior traumas, PTSD symptoms, depression, anxiety, substance use, health and services, using validated survey instruments.

Results: Of 1362 women seen for prenatal intakes, 1259 (92 %) were screened, 208 (17 %) screened positive for PTSD at clinical (11 %) or sub-threshold levels (6 %), and 149 (72 % of all eligible women) enrolled in the study. Those screening positive were significantly younger, had more prior pregnancies, were less likely to be Asian or black, and were more likely to be non-English speakers. Enrolled women at clinical as compared to sub-threshold levels showed few differences in psychosocial risk, but had significantly more types of trauma, more trauma before age 18, more interpersonal trauma, and had greater depression, anxiety, and PTSD symptoms. Only about 25 % had received mental health treatment.

Conclusions: The PTSD-PC was a feasible screening tool for use in prenatal care. While those screening in at clinical levels were more symptomatic, those at subthreshold levels still showed substantial symptomology and psychosocial risk.

Group B Streptococcus Degrades Cyclic-di-AMP to Modulate STING-Dependent Type I Interferon Production

Tue, 10/11/2016 - 3:45pm

Induction of type I interferon (IFN) in response to microbial pathogens depends on a conserved cGAS-STING signaling pathway. The presence of DNA in the cytoplasm activates cGAS, while STING is activated by cyclic dinucleotides (cdNs) produced by cGAS or from bacterial origins. Here, we show that Group B Streptococcus (GBS) induces IFN-beta production almost exclusively through cGAS-STING-dependent recognition of bacterial DNA. However, we find that GBS expresses an ectonucleotidase, CdnP, which hydrolyzes extracellular bacterial cyclic-di-AMP. Inactivation of CdnP leads to c-di-AMP accumulation outside the bacteria and increased IFN-beta production. Higher IFN-beta levels in vivo increase GBS killing by the host. The IFN-beta overproduction observed in the absence of CdnP is due to the cumulative effect of DNA sensing by cGAS and STING-dependent sensing of c-di-AMP. These findings describe the importance of a bacterial c-di-AMP ectonucleotidase and suggest a direct bacterial mechanism that dampens activation of the cGAS-STING axis.

Adapting Open Dialogue for Early-Onset Psychosis Into the U.S. Health Care Environment: A Feasibility Study

Tue, 10/11/2016 - 3:45pm

Open Dialogue (OD) is a Finnish approach to crisis intervention and ongoing care for young people experiencing psychosis and other psychiatric crises. OD engages the individual and family (or other supports) in meetings, with open discussions of all aspects of the clinical situation, and in decision making. Although psychiatric assessment and treatment occur, the initial emphasis is on engagement, crisis intervention, and promoting dialogue. Finnish studies are encouraging, with excellent clinical and functional outcomes after five years. The authors conducted a one-year study of the feasibility of implementing an outpatient program based on OD principles, serving 16 young people ages 14-35 experiencing psychosis-the first study of OD in the United States. Qualitative and quantitative findings suggest that this model can be successfully implemented in the United States and can achieve good clinical outcomes, high satisfaction, and shared decision making.

The Vascular Quality Initiative Cardiac Risk Index for prediction of myocardial infarction after vascular surgery

Tue, 10/11/2016 - 3:45pm

OBJECTIVE: The objective of this study was to develop and to validate the Vascular Quality Initiative (VQI) Cardiac Risk Index (CRI) for prediction of postoperative myocardial infarction (POMI) after vascular surgery.

METHODS: We developed risk models for in-hospital POMI after 88,791 nonemergent operations from the VQI registry, including carotid endarterectomy (CEA; n = 45,340), infrainguinal bypass (INFRA; n = 18,054), suprainguinal bypass (SUPRA; n = 2678), endovascular aneurysm repair (EVAR; n = 18,539), and open abdominal aortic aneurysm repair (OAAA repair; n = 4180). Multivariable logistic regression was used to create an all-procedure and four procedure-specific risk calculators based on the derivation cohort from 2012 to 2014 (N = 61,236). Generalizability of the all-procedure model was evaluated by applying it to each procedure subtype. The models were validated using a cohort (N = 27,555) from January 2015 to February 2016. Model discrimination was measured by area under the receiver operating characteristic curve (AUC), and performance was validated by bootstrapping 5000 iterations. The VQI CRI calculator was made available on the Internet and as a free smart phone app available through QxCalculate.

RESULTS: Overall POMI incidence was 1.6%, with variation by procedure type as follows: CEA, 0.8%; EVAR, 1.0%; INFRA, 2.6%; SUPRA, 3.1%; and OAAA repair, 4.3% (P < .001). Predictors of POMI in the all-procedure model included age, operation type, coronary artery disease, congestive heart failure, diabetes, creatinine concentration > 1.8 mg/dL, stress test status, and body mass index (AUC, 0.75; 95% confidence interval [CI], 0.73-0.76). The all-procedure model demonstrated only minimally reduced accuracy when it was applied to each procedure, with the following AUCs: CEA, 0.65 (95% CI, 0.59-0.70); INFRA, 0.69 (95% CI, 0.64-0.73); EVAR, 0.72 (95% CI, 0.65-0.80); SUPRA, 0.62 (95% CI, 0.52-0.72); and OAAA, 0.63 (95% CI, 0.56-0.70). Procedure-specific models had unique predictors and showed improved prediction compared with the all-procedure model, with the following AUCs: CEA, 0.69 (95% CI, 0.66-0.72); INFRA, 0.75 (95% CI, 0.73-0.78); EVAR, 0.76 (95% CI, 0.73-0.80); and OAAA, 0.72 (95% CI, 0.69-0.77). Bias-corrected AUC (95% CI) from internal validation for the models was as follows: all procedures, 0.75 (0.73-0.76); CEA, 0.68 (0.65-0.71); INFRA, 0.74 (0.72-0.76); EVAR, 0.73 (0.70-0.78); and OAAA repair, 0.68 (0.65-0.73).

CONCLUSIONS: The VQI CRI is a useful and valid clinical decision-making tool to predict POMI after vascular surgery. Procedure-specific models improve accuracy when they include unique risk factors.

Dynamics of dengue virus-specific B cells in the response to dengue virus-1 infections using flow cytometry with labeled virions

Tue, 10/11/2016 - 3:45pm

BACKGROUND: The development of reagents to identify and characterize antigen-specific B cells has been challenging.

METHODS: We recently developed Alexa Fluor-labeled dengue viruses (AF DENV) to characterize antigen-specific B cells in the peripheral blood of DENV-immune individuals.

RESULTS: In this study, we used AF DENV-1 together with AF DENV-2 on PBMC from children in Thailand undergoing acute primary or secondary DENV-1 infections to analyze the phenotypes of antigen-specific B cells that reflected their exposure or clinical diagnosis. DENV serotype-specific and cross-reactive B cells were identified in PBMC from all subjects. Frequencies of AF-DENV+ class switched memory B cells (IgD-CD27+ CD19+ cells) reached up to 8% during acute infection and early convalescence. AF DENV-labeled B cells expressed high levels of CD27 and CD38 during acute infection, characteristic of plasmablasts, and transitioned into memory B cells (CD38-CD27+) at the early convalescent time point. There was higher activation of memory B cells early during acute secondary infection suggesting reactivation from a previous DENV infection.

CONCLUSIONS: AF DENV reveal changes in the phenotype of DENV serotype-specific and cross-reactive B cells during and after natural DENV infection and could be useful in analysis of the response to DENV vaccination.

Micronutrient Intake among Children in Puerto Rico: Dietary and Multivitamin-Multimineral Supplement Sources

Tue, 10/11/2016 - 3:45pm

BACKGROUND: Micronutrients are critical for healthy growth and development of children. Micro-nutrient intake from dietary sources is inadequate among some children and may be improved by use of multivitamin and multimineral (MVMM) supplements.

OBJECTIVE: To assess micronutrient intake from dietary and MVMM supplement sources among 12-year-old children in Puerto Rico.

METHODS: A representative sample of 732 children enrolled in an oral health study in Puerto Rico, who completed dietary and MVMM assessments through one 24-h recall, were included in this analysis. Micronutrient intake sources were described and compared to the Dietary Reference Intakes (DRIs) using the Estimated Average Requirement when available (used Adequate Intake for vitamin K and pantothenic acid). Micronutrient profiles of MVMM users and non-users were compared using t-tests.

RESULTS: Mean intakes of vitamins A, D, E, and K, pantothenic acid, cal-cium, and magnesium from food and beverage sources were below the DRIs. From food and beverage sources, MVMM users had higher intakes of riboflavin and folate compared to non-users (p < 0.05). When MVMM supplements were taken into account, users had higher in-takes of all nutrients except vitamin K. With the help of MVMM, users increased intake of vita-mins E, A, D, and pantothenic acid to IOM-recommended levels but calcium, magnesium, and vitamin K remained below guidelines.

CONCLUSION: Micronutrient intake from diet was below the IOM-recommended levels in the total sample. MVMM use improved intake of selected micronu-trients and facilitated meeting recommendations for some nutrients. Public health measures to improve micronutrient intake among children in Puerto Rico are needed.

Influential Factors of Puerto Rican Mother-Child Communication About Sexual Health Topics

Tue, 10/11/2016 - 3:45pm

Introduction: Latina mothers play a central role in raising and socializing their children; however, few studies have examined the cultural, socio-cognitive and neighborhood-related variables influencing the level of communication between Puerto Rican mothers and their children about sexuality and sexual health. This cross-sectional study sought to examine these influences.

Methods: Puerto Rican mothers with children aged 10-19 years (n = 193) were selected randomly for an ethnographic interview as part of a community participatory action research project in a U.S. urban northeastern community.

Results: Bivariate analyses found statistically significant associations between the child's age (p = 0.002), the mother's past communication about traditional gender role norms of women (marianismo) (p < 0.001), her positive outcome expectations for communications with her child (p < 0.025), and her perceptions of the physical condition (p < 0.001) and sexual health problems (p = 0.047) in the neighborhood. In a multivariate model, all of these variables remained significant except sexual health problems, and mother's attitudes toward the obligations of children to parents (familismo) emerged as a factor associated with a decrease in the number of sexual health topics that mothers raised with their children. No significant effects were found for mother's spiritual and religious experience (religiosidad).

Discussion: Our study highlights the importance of marianismo as a framework within which Puerto Rican mothers communicate sexual health information as well as the need to improve mothers' confidence discussing sexual health issues with their children. Future public health interventions to promote communication about sexuality and sexual health among Puerto Rican mothers should consider addressing this issue as a part of comprehensive neighborhood improvement projects.

Implementation of treat-to-target in rheumatoid arthritis through a Learning Collaborative: Rationale and design of the TRACTION trial

Tue, 10/11/2016 - 3:45pm

BACKGROUND/PURPOSE: Treat-to-target (TTT) is a recommended strategy in the management of rheumatoid arthritis (RA), but various data sources suggest that its uptake in routine care in the US is suboptimal. Herein, we describe the design of a randomized controlled trial of a Learning Collaborative to facilitate implementation of TTT.

METHODS: We recruited 11 rheumatology sites from across the US and randomized them into the following two groups: one received the Learning Collaborative intervention in Phase 1 (month 1-9) and the second formed a wait-list control group to receive the intervention in Phase 2 (months 10-18). The Learning Collaborative intervention was designed using the Model for Improvement, consisting of a Change Package with corresponding principles and action phases. Phase 1 intervention practices had nine learning sessions, collaborated using a web-based tool, and shared results of plan-do-study-act cycles and monthly improvement metrics collected at each practice. The wait-list control group sites had no intervention during Phase 1. The primary trial outcome is the implementation of TTT as measured by chart review, comparing the differences from baseline to end of Phase 1, between intervention and control sites.

RESULTS: All intervention sites remained engaged in the Learning Collaborative throughout Phase 1, with a total of 38 providers participating. The primary trial outcome measures are currently being collected by the study team through medical record review.

CONCLUSIONS: If the Learning Collaborative is an effective means for improving implementation of TTT, this strategy could serve as a way of implementing disseminating TTT more widely.

Peripartum neuroactive steroid and gamma-aminobutyric acid profiles in women at-risk for postpartum depression

Tue, 10/11/2016 - 3:45pm

Neuroactive steroids (NAS) are allosteric modulators of the gamma-aminobutyric acid (GABA) system. NAS and GABA are implicated in depression. The peripartum period involves physiologic changes in NAS which may be associated with peripartum depression and anxiety. We measured peripartum plasma NAS and GABA in healthy comparison subjects (HCS) and those at-risk for postpartum depression (AR-PPD) due to current mild depressive or anxiety symptoms or a history of depression. We evaluated 56 peripartum medication-free subjects. We measured symptoms with the Hamilton Depression Rating Scale (HAM-D17), Hamilton Anxiety Rating Scale (HAM-A) and Spielberger State-Trait Anxiety Inventory-State (STAI-S). Plasma NAS and GABA were quantified by liquid chromatography-mass spectrometry. We examined the associations between longitudinal changes in NAS, GABA and depressive and anxiety symptoms using generalized estimating equation methods. Peripartum GABA concentration was 1.9+/-0.7ng/mL (p=0.004) lower and progesterone and pregnanolone were 15.8+/-7.5 (p=0.04) and 1.5+/-0.7ng/mL (p=0.03) higher in AR-PPD versus HCS, respectively. HAM-D17 was negatively associated with GABA (beta=-0.14+/-0.05, p=0.01) and positively associated with pregnanolone (beta=0.16+/-0.06, p=0.01). STAI-S was positively associated with pregnanolone (beta=0.11+/-0.04, p=0.004), allopregnanolone (beta=0.13+/-0.05, p=0.006) and pregnenolone (beta=0.02+/-0.01, p=0.04). HAM-A was negatively associated with GABA (beta=-0.12+/-0.04, p=0.004) and positively associated with pregnanolone (beta=0.11+/-0.05, p=0.05). Altered peripartum NAS and GABA profiles in AR-PPD women suggest that their interaction may play an important role in the pathophysiology of peripartum depression and anxiety.

Assessing patients' experiences with communication across the cancer care continuum

Tue, 10/11/2016 - 3:45pm

OBJECTIVE: To evaluate the relevance, performance and potential usefulness of the Patient Assessment of cancer Communication Experiences (PACE) items.

METHODS: Items focusing on specific communication goals related to exchanging information, fostering healing relationships, responding to emotions, making decisions, enabling self-management, and managing uncertainty were tested via a retrospective, cross-sectional survey of adults who had been diagnosed with cancer. Analyses examined response frequencies, inter-item correlations, and coefficient alpha.

RESULTS: A total of 366 adults were included in the analyses. Relatively few selected Does Not Apply, suggesting that items tap relevant communication experiences. Ratings of whether specific communication goals were achieved were strongly correlated with overall ratings of communication, suggesting item content reflects important aspects of communication. Coefficient alpha was > /=.90 for each item set, indicating excellent reliability. Variations in the percentage of respondents selecting the most positive response across items suggest results can identify strengths and weaknesses.

CONCLUSION: The PACE items tap relevant, important aspects of communication during cancer care, and may be useful to cancer care teams desiring detailed feedback.

PRACTICE IMPLICATIONS: The PACE is a new tool for eliciting patients' perspectives on communication during cancer care. It is freely available online for practitioners, researchers and others.

Factors associated with patient activation in an older adult population with functional difficulties

Tue, 10/11/2016 - 3:45pm

OBJECTIVE: Patient activation, the patient's knowledge, skill, and confidence to manage his or her health, is an important indicator of future health and use of health care resources. Understanding factors associated with patient activation in an older population with functional difficulties may inform care in this population. This study aimed to determine whether patient activation is associated with depression, chronic conditions, family support, difficulties with activities of daily living (ADLs) and instrumental activities of daily living (IADLs), hospitalizations, education, and financial strain.

METHODS: (N=277), We administered surveys measuring patient activation, financial strain, depressive symptoms, family support, and chronic conditions to an older adult population. We tested association through multivariate linear regressions controlling for race, sex, and age.

RESULTS: Patient activation is significantly (p < 0.05), positively associated with family support and self-rated overall health, and significantly (p < 0.05), negatively associated with depressive symptoms and difficulties with ADLs and IADLs. We found no association between patient activation and financial stress, hospitalizations, and education.

CONCLUSIONS: Older age, depressive symptoms, and difficulties with ADLs and IADLs were associated with decreased patient activation.

PRACTICE IMPLICATIONS: Developing interventions tailored to older adults' level of patient activation has the potential to improve outcomes for this population.

Control of the innate immune response by the mevalonate pathway

Tue, 10/11/2016 - 3:45pm

Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110delta. Macrophages that were deficient in GGTase I or p110delta exhibited constitutive release of interleukin 1beta that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome.

Racial/Ethnic Disparities in Meeting 5-2-1-0 Recommendations among Children and Adolescents in the United States

Tue, 10/11/2016 - 3:44pm

OBJECTIVE: To evaluate racial/ethnic disparities among children and adolescents in meeting the 4 daily 5-2-1-0 nutrition and activity targets in a nationally representative sample. The 5-2-1-0 message summarizes 4 target daily behaviors for obesity prevention: consuming > /=5 servings of fruit and vegetables, engaging in < /=2 hours of screen time, engaging in > /=1 hour of physical activity, and consuming 0 sugar-sweetened beverages daily. STUDY DESIGN: The National Health and Nutrition Examination Survey (2011-2012) data were used. The study sample included Hispanic (n = 608), non-Hispanic black (n = 609), Asian (n = 253), and non-Hispanic white (n = 484) youth 6-19 years old. The 5-2-1-0 targets were assessed using 24-hour dietary recalls, the Global Physical Activity Questionnaire, and sedentary behavior items. Outcomes included meeting all targets, no targets, and individual targets. Multivariable logistic regression models accounting for the complex sampling design were used to evaluate the association of race/ethnicity with each outcome among children and adolescents separately. RESULTS: None of the adolescents and <1% of children met all 4 of the 5-2-1-0 targets, and 19% and 33%, of children and adolescents, respectively, met zero targets. No racial/ethnic differences in meeting zero targets were observed among children. Hispanic (aOR, 1.76 [95% CI, 1.04-2.98]), non-Hispanic black (aOR, 1.82 [95% CI, 1.04-3.17]), and Asian (aOR, 1.48 [95% CI, 1.08-2.04]) adolescents had greater odds of meeting zero targets compared with non-Hispanic whites. Racial/ethnic differences in meeting individual targets were observed among children and adolescents. CONCLUSIONS: Despite national initiatives, youth in the US are far from meeting 5-2-1-0 targets. Racial/ethnic disparities exist, particularly among adolescents.