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Metropolitan Government of Nashville-Davidson (balance), TN, United States

BACKGROUND: Undernourished, HIV-infected adults in sub-Saharan Africa have high levels of systemic inflammation, which is a risk factor for mortality and other adverse health outcomes. We hypothesized that microbial translocation, due to the deleterious effects of HIV and poor nutrition on intestinal defenses and mucosal integrity, contributes to heightened systemic inflammation in this population, and reductions in inflammation on antiretroviral therapy (ART) accompany reductions in translocation.METHODS: HIV-infected, Zambian adults with a body mass index <18.5 kg/m2 were recruited for a pilot study to assess the relationships between microbial translocation and systemic inflammation over the first 12 weeks of ART. To assess microbial translocation we measured serum lipopolysaccharide binding protein (LBP), endotoxin core IgG and IgM, and soluble CD14, and to assess intestinal permeability we measured the urinary excretion of an oral lactulose dose normalized to urinary creatinine (Lac/Cr ratio). Linear mixed models were used to assess within-patient changes in these markers relative to serum C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 over 12 weeks, in addition to relationships between variables independent of time point and adjusted for age, sex, and CD4+ count.RESULTS: Thirty-three participants had data from recruitment and at 12 weeks: 55% were male, median age was 36 years, and median baseline CD4+ count was 224 cells/μl. Over the first 12 weeks of ART, there were significant decreases in serum levels of LBP (median change -8.7 μg/ml, p = 0.01), TNF-α receptor 1 (-0.31 ng/ml, p < 0.01), and CRP (-3.5 mg/l, p = 0.02). The change in soluble CD14 level over 12 weeks was positively associated with the change in CRP (p < 0.01) and soluble CD163 (p < 0.01). Pooling data at baseline and 12 weeks, serum LBP was positively associated with CRP (p = 0.01), while endotoxin core IgM was inversely associated with CRP (p = 0.01) and TNF-α receptor 1 (p = 0.04). The Lac/Cr ratio was not associated with any serum biomarkers.CONCLUSIONS: In undernourished HIV-infected adults in Zambia, biomarkers of increased microbial translocation are associated with high levels of systemic inflammation before and after initiation of ART, suggesting that impaired gut immune defenses contribute to innate immune activation in this population. Source


Andrews J.C.,Vanderbilt University | Andrews J.C.,Vanderbilt Institute for Global Health
Obstetrical and Gynecological Survey | Year: 2011

Introduction: State of the art guidance exists for management of vulvodynia, but the scientific basis for interventions has not been well described. Although there are many interventional therapies, and their use is increasing, there is also uncertainty or controversy about their efficacy. Objective: To systematically assess benefits and harms of interventional therapies for vulvodynia and vestibulodynia. Methods: The following databases were searched, using MeSH terms for studies related to the treatment of vulvodynia or vulva pain/pruritus/dysesthesia/hyperesthesia/hypersensitivity: MEDLINE, PsycINFO, Scopus, Cochrane Library, EBSCO Academic, and Google Scholar. Using Medical Subject Reference sections of relevant original articles, reviews, and evidence-based guidelines were screened manually. Manual searching for indirect evidence supporting interventions was done whenever no direct evidence was found for a treatment described within a review or guideline. Each modality is assessed with a grading system similar to the Grades of Recommendation, Assessment, Development, and Evaluation system. The grading system assesses study quality, effect size, benefits, risks, burdens, and costs. Results: For improvement of pain and/or function in women with vestibulodynia (provoked localized vulvodynia), there was fair evidence that vestibulectomy was of benefit, but the size of the effect cannot be determined with confidence. There was good evidence of a placebo effect from multiple studies of nonsurgical interventions. There was fair evidence of lack of efficacy for several nonsurgical interventions. There were several interventions for which there were insufficient evidence to reliably evaluate. There was insufficient evidence to judge harms or to judge long-term benefits.For clinically meaningful improvement of pain in women with generalized unprovoked vulvodynia, there was insufficient evidence for benefit of any intervention. There was fair evidence of a placebo effect in people with neuropathic pain and functional pain syndromes, from multiple studies of interventions. Based on indirect evidences from studies of patients with other pain disorders, interventions may be selected for future research. Conclusion: There is fair evidence for effectiveness of vestibulectomy for vestibulodynia; however, there is uncertainty about the size of the absolute effect, because of the risk of bias inherent in studies of pain interventions without a placebo control group. Providers and patients looking for evidence-based interventions for generalized unprovoked vulvodynia may need to rely on indirect evidences from studies of neuropathic pain and functional pain syndromes. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this educational activity, the obstetrician/gynecologist should be better able to identify potential causes of vulvar pain to facilitate diagnosis of vulvodynia and vestibulodynia, distinguish between the symptoms of localized, provoked vulvodynia and generalized unprovoked vulvodynia to select the most appropriate therapies, evaluate the efficacy of surgical and nonsurgical interventions for the treatment of generalized unprovoked and localized, provoked vulvodynia. In addition, assess the benefits and risks of interventional therapies for vulvodynia and vestibulodynia to improve patient care. © 2011 by Lippincott Williams & Wilkins. Source


Hickey M.C.,University of California at Davis | Jandrey K.,University of California at Davis | Farrell K.S.,University of California at Davis | Carlson-Bremer D.,Vanderbilt Institute for Global Health
Journal of Veterinary Internal Medicine | Year: 2014

Background: Renal infarcts identified without definitive association with any specific disease process. Objective: Determine diseases associated with diagnosis of renal infarcts in cats diagnosed by sonography or necropsy. Animals: 600 cats underwent abdominal ultrasonography, necropsy, or both at a veterinary medical teaching hospital. Methods: Information obtained from electronic medical records. Cats classified as having renal infarct present based on results of sonographic evaluation or necropsy. Time-matched case-controls selected from cats that underwent the next scheduled diagnostic procedure. Results: 309 of 600 cats having diagnosis of renal infarct and 291 time-matched controls. Cats 7-14 years old were 1.6 times (odds ratio, 95% CI: 1.03-2.05, P = .03) more likely to have renal infarct than younger cats but no more likely to have renal infarct than older cats (1.4, 0.89-2.25, P = .14). All P = .14 are statistically significant. Cats with renal infarcts were 4.5 times (odds ratio, 95% CI: 2.63-7.68, P < .001) more likely to have HCM compared to cats without renal infarcts. Cats with renal infarcts were 0.7 times (odds ratio, 95% CI: 0.51-0.99, P = .046) less likely to have diagnosis of neoplasia compared to cats without renal infarcts. Cats with diagnosis of hyperthyroidism did not have significant association with having renal infarct. Cats with renal infarcts were 8 times (odds ratio, 95% CI: 2.55-25.40, P ≤ .001) more likely to have diagnosis of distal aortic thromboembolism than cats without renal infarcts. Conclusions and Clinical Importance: Cats with renal infarcts identified on antemortem examination should be screened for occult cardiomyopathy. © 2014 by the American College of Veterinary Internal Medicine. Source


Davis T.O.M.,Vanderbilt University | Fischer E.,Vanderbilt University | Rohloff P.,Brigham and Womens Hospital | Heimburger D.,Vanderbilt Institute for Global Health
Human Organization | Year: 2014

Ready To Use Therapeutic Food (RUTF) and Ready To Use Supplementary Food (RUSF) have proliferated in recent years to treat acute and chronic malnutrition. Bio Medical research has established the efficacy of these products, yet little is known about their actual effectiveness in real world settings. This article reports on an ethnographic study of the acceptance and use of RUSF within households in a rural Maya co Mmunity in Guatemala (a country with the world's third highest rate of chronic malnutrition). We find a number of surprising obstacles to RUSF effectiveness. There is a strong co Mmitment to breastfeeding (supported by public health messages of local NGOs as well as culturally perceived benefits) that leads to sub-optimal co Mplementary feeding after six months. We also found instances of off-label sharing and confusion over relative nutritional values. We present a framework for maximizing RUSF effectiveness that involves nutritional education, positive peer support, and the framing of the product as a medicine. Source


Koethe J.R.,Vanderbilt University | Koethe J.R.,Center for Infectious Disease Research in Zambia | Heimburger D.C.,Vanderbilt Institute for Global Health | Heimburger D.C.,Center for Infectious Disease Research in Zambia | Heimburger D.C.,University of Alabama at Birmingham
American Journal of Clinical Nutrition | Year: 2010

The twin global epidemics of HIV infection and food scarcity disproportionately affect sub-Saharan Africa, and a significant proportion of patients who require antiretroviral therapy (ART) are malnourished because of a combination of HIV-associated wasting and inadequate nutrient intake. Protein-calorie malnutrition, the most common form of adult malnutrition in the region, is associated with significant morbidity and compounds the immunosuppressive effects of HIV. A low body mass index (BMI), a sign of advanced malnutrition, is an independent predictor of early mortality (<6 mo) after ART initiation in several analyses, and recent studies show an association between early weight gain when receiving ART and improved treatment outcomes. The cause of the observed increase in mortality is uncertain, but it is likely due in part to malnutritioninduced immune system dysfunction, a higher burden of opportunistic infections, and metabolic derangements. In this article, we describe the epidemiology of HIV infection and malnutrition in sub-Saharan Africa, potential causes of increased mortality after ART initiation among patients with a low BMI, recent studies on post-ART weight gain and treatment outcome, and trials of macronutrient supplementation from the region. We close by highlighting priority areas for future research. © 2010 American Society for Nutrition. Source

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