Publications

Clinical and translational research increasingly requires computation. Projects may involve multiple computationally oriented groups including information technology (IT) professionals, computer scientists, and biomedical informaticians. However, many biomedical researchers are not aware of the distinctions among these complementary groups, leading to confusion, delays, and suboptimal results. Although written from the perspective of Clinical and Translational Science Award (CTSA) programs within academic medical centers, this article addresses issues that extend beyond clinical and translational research. The authors describe the complementary but distinct roles of operational IT, research IT, computer science, and biomedical informatics using a clinical data warehouse as a running example. In general, IT professionals focus on technology. The authors distinguish between two types of IT groups within academic medical centers: central or administrative IT (supporting the administrative computing needs of large organizations) and research IT (supporting the computing needs of researchers). Computer scientists focus on general issues of computation such as designing faster computers or more efficient algorithms, rather than specific applications. In contrast, informaticians are concerned with data, information, and knowledge. Biomedical informaticians draw on a variety of tools, including but not limited to computers, to solve information problems in health care and biomedicine. The paper concludes with recommendations regarding administrative structures that can help to maximize the benefit of computation to biomedical research within academic health centers.

STUDY OBJECTIVE

To determine clinical and microbiologic outcomes of daptomycin for the treatment of bacteremia caused by vancomycin-resistant enterococci (VRE).

DESIGN

Retrospective medical record review.

SETTING

Academic tertiary care hospital.

PATIENTS

Thirty patients (median age 59 yrs, range 19-79 yrs, 50% male) who received daptomycin for the treatment of VRE bacteremia between January 2004 and July 2007.

MEASUREMENTS AND MAIN RESULTS

Patients were included if they received daptomycin and had a blood culture positive for VRE at the time daptomycin was started. The primary end point was microbiologic cure, defined as negative blood cultures for VRE at the end of therapy. Secondary outcomes were clinical outcomes, adverse events, and occurrence of elevated creatine kinase levels. Clinical outcomes were judged as positive, negative, or indeterminate. The median Acute Physiology and Chronic Health Evaluation (APACHE) II score was 17 (range 7-34), and 20 patients (67%) were in the intensive care unit. Patients received daptomycin for a median of 13 days (range 1-42 days), and the median dose administered was 6 mg/kg (range 3.7-8 mg/kg). Microbiologic cure was achieved in 24 patients (80%), and clinical success occurred in 17 patients (59% [one patient had an indeterminate clinical outcome and was excluded from this analysis]). All patients with a positive clinical outcome had microbiologic cure, six patients who died had microbiologic cure, and all patients with microbiologic failure died. On multivariable logistic regression, higher APACHE II score was associated with a lower chance of microbiologic success (adjusted odds ratio [AOR] 0.73, 95% confidence interval [CI] 0.56-0.95). Lower APACHE II score (AOR 0.86, 95% CI 0.74-1.0) and daptomycin dose of 6 mg/kg or more (AOR 7.29, 95% CI 1.02-52.0) were associated with clinical success. Adverse drug events possibly attributable to daptomycin were uncommon. Three patients had fever possibly related to daptomycin, and two patients had mild elevations of creatine kinase level.

CONCLUSION

Our experience suggests that daptomycin may be an acceptable option for VRE bacteremia; however, larger studies should be performed before this antimicrobial is routinely used for this indication.

OBJECTIVE

To examine the long-term effects of individual antiretroviral drugs on body composition among 416 persons initiating antiretroviral therapy (ART).

METHODS

In a substudy of a clinical trial of persons initiating ART, changes in body composition attributable to individual ART were examined. ARTs assessed were as follows: indinavir, ritonavir, nelfinavir, efavirenz, nevirapine, stavudine (d4T), zidovudine (ZDV), lamivudine (3TC), didanosine, and abacavir. Skinfolds and circumferences were measured at baseline and every 4 months. Mid arm, mid thigh, and waist subcutaneous tissue areas and nonsubcutaneous tissue areas were calculated. Rates of change per year of exposure to each individual ART drug were determined using multivariate longitudinal regression.

RESULTS

d4T and ZDV use was associated with losses in subcutaneous tissue area and skinfold thickness. 3TC use was associated with gains in all subcutaneous tissue areas and skinfold thickness, whereas abacavir use was associated with an increase in waist subcutaneous tissue area. Indinavir was associated with gains in waist subcutaneous tissue area, whereas indinavir, efavirenz, and nevirapine were associated with increases in upper back skinfolds. d4T use was also associated with increases in all nonsubcutaneous tissue areas; 3TC use was associated with the greatest increase in waist nonsubcutaneous tissue area.

CONCLUSION

In this prospective nonrandomized evaluation, the nucleoside reverse transcriptase inhibitors d4T and ZDV were associated with decreases in subcutaneous tissue areas, whereas 3TC use was associated with increased subcutaneous tissue areas and waist nonsubcutaneous tissue area.

Chronic prostatitis is a common disease of unclear etiology and has no specific treatment. Mice deficient in the expression of the autoimmune regulator (Aire) gene, which are defective in thymic expression of self antigens and central tolerance, develop spontaneous prostatitis. In this study, we found that Aire-deficient mice developed spontaneous B and T cell immune responses to a prostate autoantigen, seminal vesicle secretory protein 2 (SVS2), which we believe to be novel. We show that thymic expression of this self antigen was Aire dependent. Moreover, prostatitis was induced in WT mice through immunization with SVS2, demonstrating that immunity to SVS2 was sufficient to induce prostatitis. The clinical relevance of this antigen was highlighted by our observation that patients with chronic prostatitis possessed specific autoantibodies against the human SVS2-like seminal vesicle protein semenogelin. These results provide direct evidence that spontaneous chronic prostatitis is an autoimmune disease and is regulated by both central and peripheral tolerance. Moreover, SVS2 and semenogelin are among the relevant autoantigens in mice and humans, respectively.

Olfaction and nasal trigeminal chemoreception together convey an impression of the physical and chemical qualities of inspired air. "Nasal pungency" refers to the nasal trigeminal impact of inhaled air pollutants as well as spicy foods and selected medicaments. Such diverse sensations as cooling, numbness, tingling, itching, burning, and stinging are all conveyed by the trigeminal system yet are successfully differentiated in psychophysical testing, with or without concomitant olfactory information. Here we briefly review the neurobiological and psychophysical evidence for qualitative specificity in the nasal trigeminal system.