Carlos Grijalva - US grants

[unreadable] DESCRIPTION (provided by applicant): Influenza, a vaccine-preventable disease, remains as an important cause of morbidity and mortality worldwide. All age groups are affected, but children experience the highest disease incidence while adults suffer the most serious disease complications and related mortality. The burden of seasonal influenza epidemics and the continuous threat of a potential pandemic influenza highlight the need for effective preventive strategies. During influenza epidemics, children are typically affected early and they serve as disease vectors, introducing influenza into the community. Influenza vaccines have proven to be efficacious in the prevention of disease in vaccinated individuals and it has been hypothesized that immunization of a significant proportion of children could have major beneficial effects in the community, through the interruption of influenza transmission. Therefore, school-based influenza immunization programs have been proposed as prevention models. Nevertheless, the effectiveness of these approaches has not been convincingly demonstrated in large scale interventions. If proven effective, school-based influenza immunizations could become one major strategy for prevention of both seasonal and pandemic influenza. In October 2005, a large school-based influenza immunization campaign was initiated in Knox County, TN. The campaign was successfully implemented, immunizing 24,281 (46%) school-aged children attending public schools in the county. The campaign achieved at least similar coverage in the subsequent 2006-2007 influenza season. Although this campaign was set up as a feasibility demonstration project, its impact on disease outcomes has not been examined. We hypothesize that this large 2-year intervention decreased the incidence of influenza related diseases in both vaccinated and unvaccinated Knox County residents. Vanderbilt investigators are currently performing active viral surveillance in Knox County (intervention) and Davidson County (control) to compare viral activity during the second year of the campaign (2006-2007 season). We propose to perform additional and complementary analyses using alternate data sources to measure the overall intervention effectiveness (direct and indirect effects) over both intervention years. We will utilize large electronic databases that systematically record healthcare encounters in the State of Tennessee, and the infrastructure and expertise of the New Vaccine Surveillance Network (NVSN), a prospective surveillance system for viral infections in children that is currently operating in Tennessee. The proposed research and career development plan complement Dr. Grijalva's training in Medicine, Public Health and Epidemiology. Furthermore, this proposal supports his efforts to develop the expertise needed to become an independent investigator focused on prevention of influenza-related morbidity and mortality and on vaccine program and policy evaluations. [unreadable] [unreadable] [unreadable]

SES-0750704
Jon Gjerde
Gloria Chun
Angela James
Beth Schneider
University of California, Berkeley

A three-year grant was provided to the UC-DIGSSS Alliance (University of California Diversity Initiative for Graduate Study in the Social Sciences)comprised of the University of California at Berkeley, Los Angeles, Santa Barbara, to complete a pilot program to broaden the participation of underrepresented minority students into the social sciences. The aim of UC-DIGSSS is not only to increase the numbers of underrepresented minority students, but also to help transform the culture of the academy so that institutional environments are more attractive to underrepresented minorities. UC-DIGSS has worked closely with divisional deans, department chairs, graduate advisors and faculty to initiate a series of new programs to recruit and retain underrepresented minority students in graduate programs in the social and behavioral sciences. All three campuses have experienced increased in the number of students matriculated in social science graduate programs since the onset of the grant. UC-DIGSS plays a role within the broader Alliance for Graduate Education and the Professoriate (AGEP) community. The incorporation of SBE faculty and students has broadened the disciplinary scope of AGEP community, generating a more informed dialogue about the origins and consequences of inequalities in societies and institutions and enriching the social and educational context of programs. UC-DIGSSS, will continue to build on initial successes and move forward to:

. Form partnerships with MSIs (minority-serving institutions) to increase the applicant pool, by developing longitudinal relationships with MSIs across administration, faculty, and staff..

. Mentor underrepresented minority students with one-on-one research traineeships with faculty in the early stages (first three years) of the graduate program in order to help build research skills and to create strong bonds with faculty mentors early in their program.

. Improve retention by focusing on community building and creating support for graduate student research, including funding for tutors, writing improvement workshops, professional conference attendance, field research, and master's exam support.

The major broader impact of this program is the creation of synergy to broaden participation of underrepresented students in SBE fields not only within alliance campuses, but across the nation. This will be done by fostering a more informed dialogue about racialized identities and practices within the academy and forging collaborative efforts to increase the applicant pool and retain a greater number of students matriculating with doctorates in the social sciences.

DESCRIPTION (provided by applicant): Opioid analgesics are one of the most commonly prescribed medication classes in the United States. Although these medications have been available for medical use for decades, their safety and effectiveness remain unclear. Available data from clinical trials are limited to highly selected patients and short term efficacy outcomes. Of great concern, information on the safety profile of these medications is even more scant. Several lines of in vivo experimental evidence indicate that opioid analgesics have significant immunosuppressive properties and could render opioid users susceptible to serious, potentially life-threatening infections. The immunosuppressive effects of opioid analgesics could be particularly troublesome for the elderly, who are commonly affected by persistent pain and are already at increased risk for infections. Given concerns about the safety of alternate analgesics (e.g. NSAIDs and COX-2 inhibitors), and the increasing widespread use of opioids, the determination and quantification of this potential risk is of great public health interest. Furthermore, there are a number of opioid analgesics currently available, but not all are expected to have the same immunosuppressive properties. Identifying those opioids with the lowest propensity to facilitate serious infections will be crucial to inform the selection of analgesics for the elderly. We propose to conduct a retrospective study of elderly persons enrolled in TennCare (Tennessee Medicaid) with the following specific aims: 1) To test the hypothesis that use of opioid analgesics increases the risk of serious infections; and, 2) To test the hypothesis that there is variation of the risk of serious infections for individual opioids. Th proposed studies will use a self-controlled case-series design, in which cases serve as their own controls, cancelling out the effects of fixed measured and unmeasured confounders, allowing control of relevant time-varying covariates; and, thus, allowing an unbiased estimation of the relative risk.

DESCRIPTION (provided by applicant): There is substantial evidence that opioid analgesic use impairs immune system responses and there has been a long-standing concern that these effects increase the risk of serious, potentially life-threatening infections. In vivo studies in animal models and human subjects have demonstrated that opioids affect surrogate markers of immune functions that are crucial for prevention of serious infections, such as white cell migration and phagocytosis. Although studies have demonstrated significant dose-dependent suppression of immunological functions in animal models and humans as well as a dose-dependent increase in the risk of serious infections in animal models, the clinical relevance of these findings in humans remains unclear. These concerns are particularly relevant for older adults, who are commonly affected by pain and are at increased risk for infections. A number of opioid analgesics are currently available, but not all have the same immunosuppressive properties. Studies in animal models suggest that, taking the chemical structure of morphine as reference, opioids with hydroxyl groups at both C3 and C6 (e.g. morphine), have the strongest immunosuppressive effects, whereas modification at C3 alone (e.g. codeine) reduces immunosuppression, and substitution of a carbonyl group at C6 (e.g. hydromorphone) eliminates the immunosuppressive effects. Identifying those opioids that are the least likely to increase the risk of serious infections will be crucial to inform the selection of analgesics for vulnerable older adults. Furthermore, the immunosuppressive effects of opioids are dose-dependent and for several opioids, in vivo data suggest that concurrent use of opioids and other commonly used medications that inhibit opioid metabolism could markedly increase the serum concentration of opioids. We propose to conduct a series of studies of older adults with the following specific aims: 1) Test the hypothesis that the risk of serious infections in new users of codeine (which is metabolized to morphine) is greater than in new users of other opioids with comparable analgesic properties; 2) Test the hypothesis that the risk of serious infections in new users of morphine is greater than in new users of other opioids with comparable analgesic properties; and, 3) Test the hypothesis that concurrent use of oxycodone or methadone and strong inhibitors of their metabolism increases the risk of serious infections relative to such use without metabolic inhibitors. The proposed studies will use a retrospective cohort study design and data from Tennessee Medicaid, to compare the incidence of serious infections associated with the use of selected opioids while controlling for the effect of relevant baseline and time-varying covariates. Our research team has the combination of experience and expertise needed to successfully complete the proposed projects. The proposed studies are designed to have a high impact on the field of pain therapeutics, advance our understanding of the effects of opioid analgesics on the risk of serious infections and inform the clinical care of older adults.