San Francisco, CA, United States

Clinical Translational Science Institute

ctsi.ucsf.edu/
San Francisco, CA, United States
SEARCH FILTERS
Time filter
Source Type

News Article | April 26, 2017
Site: www.eurekalert.org

A diet supplemented with soy protein may be an effective adjunct therapy for inflammatory bowel diseases, Penn State researchers reported after completing a study that included mice and cultured human colon cells. The findings are significant because inflammatory bowel diseases -- including ulcerative colitis and Crohn's disease -- are characterized by either continuous or periodic inflammation of the colon and represent a significant risk factor for colon cancer. Also known as IBD, inflammatory bowel diseases affect nearly 4 million people worldwide and have an economic impact of more than $19 billion annually in the United States alone. The development of dietary strategies to mitigate IBD is of considerable public health importance, said Joshua Lambert, associate professor of food science in the College of Agricultural Sciences. He said his team found that soy-protein concentrate can exert antioxidant and cytoprotective effects in cultured human bowel cells and can moderate the severity of inflammation in mice that have an induced condition similar to ulcerative colitis. Zachary Bitzer and Amy Wopperer, former graduate students in the Department of Food Science and the lead researchers, substituted soy-protein concentrate into the diet of the mice and removed corresponding amounts of the other protein sources, equaling about 12 percent. They kept human equivalents in mind as they determined the amount. "We didn't want to get carried away with using doses that were really high and would crowd out all the other protein that was there," Bitzer said. "Instead, we wanted to find a scenario that was going to fit into a more human-relevant situation." The dietary soy-protein concentrate at the 12-percent dose level ameliorated body-weight loss and swelling of the spleen in the mice with induced inflammatory bowel disease. "Soy-protein concentrate mitigates markers of colonic inflammation and loss of gut barrier function in the mice with induced IBD," Wopperer said. Follow-on studies will focus on whether the results of this research with mice, published in The Journal of Nutritional Biochemistry, are readily translatable to people. Because soy protein is a widely used food ingredient -- often used as a meat substitute and commonly referred to as "texturized vegetable proteins" in ingredient lists -- Lambert believes human studies could be arranged in the near future. "Since it is already out there commercially, that makes it more straightforward," he said. "But practically speaking, the actual clinical studies are a little bit out of our area of expertise. I think the most likely thing to happen will be for us to try to identify a collaborator either through the Clinical Translational Science Institute on campus or with someone at the Penn State College of Medicine Inflammatory Bowel Disease Center." However, Lambert's laboratory soon will start a related investigation of whether the inflammation-moderating effects triggered in the mouse colons are due solely to the soy protein or also may be caused by soy fiber. Soy-protein concentrate is 70 percent protein by weight, but it also has quite a bit of soybean fiber in it, he explained. Also participating in the study were Benjamin Chrisfield, a master's degree student in food science; Ling Tao, a former doctoral student in food science; Timothy Cooper, associate professor of comparative medicine at the Penn State College of Medicine; and Jairam Vanamala, Ryan Elias and John Hayes, all associate professors of food science, Penn State. Technical assistance and primer synthesis services were provided by the Penn State Genomics Core Facility. The Pennsylvania Soybean Board, the American Institute for Cancer Research and the U.S. Department of Agriculture's Hatch Program supported this research. Both Wopperer and Bitzer were supported in part by the Roger and Barbara Claypoole Distinguished Graduate Fellowship in the College of Agricultural Sciences.


OBJECTIVE:: To provide ICU clinicians with evidence-based guidance on tested interventions that reduce or prevent alert fatigue within clinical decision support systems. DESIGN:: Systematic review of PubMed, Embase, SCOPUS, and CINAHL for relevant literature from 1966 to February 2017. PATIENTS:: Focus on critically ill patients and included evaluations in other patient care settings, as well. INTERVENTIONS:: Identified interventions designed to reduce or prevent alert fatigue within clinical decision support systems. MEASUREMENTS AND MAIN RESULTS:: Study selection was based on one primary key question to identify effective interventions that attempted to reduce alert fatigue and three secondary key questions that covered the negative effects of alert fatigue, potential unintended consequences of efforts to reduce alert fatigue, and ideal alert quantity. Data were abstracted by two reviewers independently using a standardized abstraction tool. Surveys, meeting abstracts, “gray” literature, studies not available in English, and studies with non-original data were excluded. For the primary key question, articles were excluded if they did not provide a comparator as key question 1 was designed as a problem, intervention, comparison, and outcome question. We anticipated that reduction in alert fatigue, including the concept of desensitization may not be directly measured and thus considered interventions that reduced alert quantity as a surrogate marker for alert fatigue. Twenty-six articles met the inclusion criteria. CONCLUSION:: Approaches for managing alert fatigue in the ICU are provided as a result of reviewing tested interventions that reduced alert quantity with the anticipated effect of reducing fatigue. Suggested alert management strategies include prioritizing alerts, developing sophisticated alerts, customizing commercially ­available alerts, and including end user opinion in alert selection. Alert fatigue itself is studied less frequently, as an outcome, and there is a need for more precise evaluation. Standardized metrics for alert fatigue is needed to advance the field. Suggestions for standardized metrics are provided in this document. Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.


Dahabreh I.J.,Institute for Clinical Research and Health Policy Studies | Paulus J.K.,Clinical Translational Science Institute | Paulus J.K.,Harvard University
JAMA - Journal of the American Medical Association | Year: 2011

Context: Evidence has suggested that physical and sexual activity might be triggers of acute cardiac events. Objective: To assess the effect of episodic physical and sexual activity on acute cardiac events using data from case-crossover studies. Data Sources: MEDLINE and EMBASE (through February 2, 2011) and Web of Science (through October 6, 2010). Study Selection: Case-crossover studies investigating the association between episodic physical or sexual activity and myocardial infarction (MI) or sudden cardiac death (SCD). Data Extraction: Two reviewers extracted descriptive and quantitative information from each study. We calculated summary relative risks (RRs) using random-effects metaanalysis and absolute event rates based on US data for the incidence of MI and SCD. We used the Fisher P value synthesis method to test whether habitual physical activity levels modify the triggering effect and meta-regression to quantify the interaction between habitual levels of physical activity and the triggering effect. Results: We identified 10 studies investigating episodic physical activity, 3 studies investigating sexual activity, and 1 study investigating both exposures. The outcomes of interest were MI (10 studies), acute coronary syndrome (1 study), and SCD (3 studies). Episodic physical and sexual activity were associated with an increase in the risk of MI (RR=3.45; 95% confidence interval [CI], 2.33-5.13, and RR=2.70; 95% CI, 1.48-4.91, respectively). Episodic physical activity was associated with SCD (RR=4.98; 95% CI, 1.47-16.91). The effect of triggers on the absolute rate of events was limited because exposure to physical and sexual activity is infrequent and their effect is transient; the absolute risk increase associated with 1 hour of additional physical or sexual activity per week was estimated as 2 to 3 per 10 000 person-years for MI and 1 per 10 000 person-years for SCD. Habitual activity levels significantly affected the association of episodic physical activity and MI (P<.001), episodic physical activity and SCD (P<.001), and sexual activity and MI (P=.04); in all cases, individuals with lower habitual activity levels had an increased RR for the triggering effect. For every additional time per week an individual was habitually exposed to physical activity, the RR for MI decreased by approximately 45%, and the RR for SCD decreased by 30%. Conclusion: Acute cardiac events were significantly associated with episodic physical and sexual activity; this association was attenuated among persons with high levels of habitual physical activity. ©2011 American Medical Association. All rights reserved.


Steele S.J.,Clinical Translational Science Institute
Science Translational Medicine | Year: 2010

In 2006, the National Institutes of Health (NIH) initiated the Clinical and Translational Science Awards (CTSA) program to establish premier academic sites designed to enhance the efficiency and effectiveness of translational research at the local, regional, and national levels. In February 2010, the NIH sponsored a national CTSA forum on "Promoting Efficient and Effective Collaborations Among Academia, Government, and Industry." This forum brought together a broad set of stakeholders who were charged with developing a path for promoting such partnerships. One theme, discussed in this meeting report, focused on opportunities and approaches to leverage CTSA institutions as a consortium in fostering public-private partnerships.


Djulbegovic B.,Clinical Translational Science Institute
Cochrane database of systematic reviews (Online) | Year: 2012

The proportion of proposed new treatments that are 'successful' is of ethical, scientific, and public importance. We investigated how often new, experimental treatments evaluated in randomized controlled trials (RCTs) are superior to established treatments. Our main question was: "On average how often are new treatments more effective, equally effective or less effective than established treatments?" Additionally, we wanted to explain the observed results, i.e. whether the observed distribution of outcomes is consistent with the 'uncertainty requirement' for enrollment in RCTs. We also investigated the effect of choice of comparator (active versus no treatment/placebo) on the observed results. We searched the Cochrane Methodology Register (CMR) 2010, Issue 1 in The Cochrane Library (searched 31 March 2010); MEDLINE Ovid 1950 to March Week 2 2010 (searched 24 March 2010); and EMBASE Ovid 1980 to 2010 Week 11 (searched 24 March 2010). Cohorts of studies were eligible for the analysis if they met all of the following criteria: (i) consecutive series of RCTs, (ii) registered at or before study onset, and (iii) compared new against established treatments in humans. RCTs from four cohorts of RCTs met all inclusion criteria and provided data from 743 RCTs involving 297,744 patients. All four cohorts consisted of publicly funded trials. Two cohorts involved evaluations of new treatments in cancer, one in neurological disorders, and one for mixed types of diseases. We employed kernel density estimation, meta-analysis and meta-regression to assess the probability of new treatments being superior to established treatments in their effect on primary outcomes and overall survival. The distribution of effects seen was generally symmetrical in the size of difference between new versus established treatments. Meta-analytic pooling indicated that, on average, new treatments were slightly more favorable both in terms of their effect on reducing the primary outcomes (hazard ratio (HR)/odds ratio (OR) 0.91, 99% confidence interval (CI) 0.88 to 0.95) and improving overall survival (HR 0.95, 99% CI 0.92 to 0.98). No heterogeneity was observed in the analysis based on primary outcomes or overall survival (I(2) = 0%). Kernel density analysis was consistent with the meta-analysis, but showed a fairly symmetrical distribution of new versus established treatments indicating unpredictability in the results. This was consistent with the interpretation that new treatments are only slightly superior to established treatments when tested in RCTs. Additionally, meta-regression demonstrated that results have remained stable over time and that the success rate of new treatments has not changed over the last half century of clinical trials. The results were not significantly affected by the choice of comparator (active versus placebo/no therapy). Society can expect that slightly more than half of new experimental treatments will prove to be better than established treatments when tested in RCTs, but few will be substantially better. This is an important finding for patients (as they contemplate participation in RCTs), researchers (as they plan design of the new trials), and funders (as they assess the 'return on investment'). Although we provide the current best evidence on the question of expected 'success rate' of new versus established treatments consistent with a priori theoretical predictions reflective of 'uncertainty or equipoise hypothesis', it should be noted that our sample represents less than 1% of all available randomized trials; therefore, one should exercise the appropriate caution in interpretation of our findings. In addition, our conclusion applies to publicly funded trials only, as we did not include studies funded by commercial sponsors in our analysis.


Stumbo P.J.,Clinical Translational Science Institute
Proceedings of the Nutrition Society | Year: 2013

Methods for conducting dietary assessment in the United States date back to the early twentieth century. Methods of assessment encompassed dietary records, written and spoken dietary recalls, FFQ using pencil and paper and more recently computer and internet applications. Emerging innovations involve camera and mobile telephone technology to capture food and meal images. This paper describes six projects sponsored by the United States National Institutes of Health that use digital methods to improve food records and two mobile phone applications using crowdsourcing. The techniques under development show promise for improving accuracy of food records. Copyright © 2013 The Author.


Nelson D.R.,Clinical Translational Science Institute
Liver International | Year: 2011

With the introduction of direct-acting oral antiviral agents we are on the verge of a new era that will transform the treatment landscape. This review discusses recent developments in drug discovery for hepatitis C protease inhibitors. First generation protease inhibitors will offer higher sustained viral response rates in naïve populations when combined with standard pegylated interferon and ribavirin. However, these dramatic gains will be partially offset by new challenges in viral resistance and increased adverse events. © 2011 John Wiley & Sons A/S.


Chen Y.,Clinical Translational Science Institute
Proceedings of the ACM Conference on Computer Supported Cooperative Work, CSCW | Year: 2011

A qualitative field study was conducted to explore the use of health information in the chronic care process. The findings show that health information is organized and used based on what we called chronic care cycles - the repeated rotations of a routine medical visit with the subsequent homecare period. We suggest that future system design consider chronic care cycles to facilitate the use of health information in managing chronic diseases. Copyright 2011 ACM.


Teoh D.G.,Clinical Translational Science Institute
American journal of obstetrics and gynecology | Year: 2015

OBJECTIVE: The goal of this pilot study was to evaluate adherence to the 2012 cervical cancer screening guidelines among health care providers in a large health maintenance organization.STUDY DESIGN: A cross-sectional survey evaluating knowledge, reported practices, and views of the 2012 cervical cancer screening guidelines was distributed to 325 health care providers within HealthPartners. The survey was divided into 3 sections: (1) provider demographics; (2) knowledge of the 2012 age-specific cancer screening guidelines; and (3) provider practice. Comparisons based on appropriate knowledge and practice of the guidelines were made using Fisher exact tests.RESULTS: The response rate was 42%. Of 124 respondents, 15 (12.1%) reported they were not aware of the 2012 guideline changes. Only 7 (5.7%) respondents answered all the knowledge questions correctly. A majority of respondents reported correct screening practices in the 21-29 year patient age group (65.8%) and in the >65 year patient age group (74.3%). Correct screening intervals in the 30-65 year patient age group varied by modality, with 89.3% correctly screening every 3 years with Pap smear alone, but only 57.4% correctly screening every 5 years with Pap smear + human papillomavirus cotesting. The most frequently cited reasons for not adhering were lack of knowledge of the guidelines and patient demand for a different screening interval.CONCLUSION: Adherence to the 2012 cervical cancer screening guidelines is poor due, in part, to a lack of knowledge of the guidelines. Efforts should focus on improved provider and patient education, and methods that facilitate adherence to the guidelines such as electronic health record order sets. Copyright © 2015 Elsevier Inc. All rights reserved.


Wao H.,Clinical Translational Science Institute
Systematic reviews | Year: 2013

Lung cancer is considered a terminal illness with a five-year survival rate of about 16%. Informed decision-making related to the management of a disease requires accurate prognosis of the disease with or without treatment. Despite the significance of disease prognosis in clinical decision-making, systematic assessment of prognosis in patients with lung cancer without treatment has not been performed. We conducted a systematic review and meta-analysis of the natural history of patients with confirmed diagnosis of lung cancer without active treatment, to provide evidence-based recommendations for practitioners on management decisions related to the disease. Specifically, we estimated overall survival when no anticancer therapy is provided. Relevant studies were identified by search of electronic databases and abstract proceedings, review of bibliographies of included articles, and contacting experts in the field. All prospective or retrospective studies assessing prognosis of lung cancer patients without treatment were eligible for inclusion. Data on mortality was extracted from all included studies. Pooled proportion of mortality was calculated as a back-transform of the weighted mean of the transformed proportions using the random-effects model. To perform meta-analysis of median survival, published methods were used to pool the estimates as mean and standard error under the random-effects model. Methodological quality of the studies was examined. Seven cohort studies (4,418 patients) and 15 randomized controlled trials (1,031 patients) were included in the meta-analysis. All studies assessed mortality without treatment in patients with non-small cell lung cancer (NSCLC). The pooled proportion of mortality without treatment in cohort studies was 0.97 (95% CI: 0.96 to 0.99) and 0.96 in randomized controlled trials (95% CI: 0.94 to 0.98) over median study periods of eight and three years, respectively. When data from cohort and randomized controlled trials were combined, the pooled proportion of mortality was 0.97 (95% CI: 0.96 to 0.98). Test of interaction showed a statistically non-significant difference between subgroups of cohort and randomized controlled trials. The pooled mean survival for patients without anticancer treatment in cohort studies was 11.94 months (95% CI: 10.07 to 13.8) and 5.03 months (95% CI: 4.17 to 5.89) in RCTs. For the combined data (cohort studies and RCTs), the pooled mean survival was 7.15 months (95% CI: 5.87 to 8.42), with a statistically significant difference between the two designs. Overall, the studies were of moderate methodological quality. Systematic evaluation of evidence on prognosis of NSCLC without treatment shows that mortality is very high. Untreated lung cancer patients live on average for 7.15 months. Although limited by study design, these findings provide the basis for future trials to determine optimal expected improvement in mortality with innovative treatments.

Loading Clinical Translational Science Institute collaborators
Loading Clinical Translational Science Institute collaborators