Research Spotlight

Froehlich-Grobe, K., D. Jones, M. S. Businelle, D. E. Kendzor and B. A. Balasubramanian (2016). “Impact of disability and chronic conditions on health.” Disabil Health J 9(4): 600-608.

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BACKGROUND: Today one in five Americans have a disability and nearly half of Americans experiences a chronic condition. Whether disability results from or is a risk factor for chronic conditions, the combined effects of disability and chronic conditions warrants further investigation. OBJECTIVES: Examine the added impact of chronic conditions among those with and without disability on self-reported health status and behaviors. METHODS: 2009 Behavioral Risk Factor Surveillance System (BRFSS) data were analyzed to examine the association of disability with unhealthy behaviors and poor health stratified by number of self-reported chronic conditions (0, 1, or 2+). Linear and logistic regression models accounting for the complex survey weights were used. RESULTS: Participants with disability were 6 times more likely to report fair/poor self-rated health, reported 9 more unhealthy days in a month and 6 more days in a month when poor health kept them from usual activities, were 4 times more likely to be dissatisfied with life, had greater odds of being a current smoker, and were less likely to be physically active. Presence of chronic conditions in addition to disability was associated, in a dose-response manner, with poor health status and unhealthy behaviors. CONCLUSIONS: People living with both chronic diseases and disability are at substantially increased risks for poor health status and unhealthy behaviors, further affecting effective management of their chronic conditions. Multi-level interventions in primary care and in the community that address social and environmental barriers that hinder adults with disability from adopting more healthy lifestyles and improving health are needed.

Graham, J. P., P. Authie, C. I. Yu, S. M. Zurawski, X. H. Li, F. Marches, A. L. Flamar, A. Acharya, J. Banchereau and A. K. Palucka (2016). “Targeting dendritic cells in humanized mice receiving adoptive t cells via monoclonal antibodies fused to flu epitopes.” Vaccine 34(41): 4857-4865.

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The targeting of vaccine antigens to antigen presenting cells (APC), such as dendritic cells (DCs), is a promising strategy for boosting vaccine immunogenicity and, in turn, protective and/or therapeutic efficacy. However, in vivo systems are needed to evaluate the potential of this approach for testing human vaccines. To this end, we examined human CD8(+) T-cell expansion to novel DC-targeting vaccines in vitro and in vivo in humanized mice. Vaccines incorporating the influenza matrix protein-1 (FluM1) antigen fused to human specific antibodies targeting different DC receptors, including DEC-205, DCIR, Dectin-1, and CD40, elicited human CD8(+) T-cell responses, as defined by the magnitude of specific CD8(+) T-cells to the targeted antigen. In vitro we observed differences in response to the different vaccines, particularly between the weakly immunogenic DEC-205-targeted and more strongly immunogenic CD40-targeted vaccines, consistent with previous studies. However, in humanized mice adoptively transferred (AT) with mature human T cells (HM-T), vaccines that performed weakly in vitro (i.e., DEC-205, DCIR, and Dectin-1) gave stronger responses in vivo, some resembling those of the strongly immunogenic CD40-targeted vaccine. These results demonstrate the utility of the humanized mouse model as a platform for studies of human vaccines.

Singh, N., C. D. Sifri, F. P. Silveira, R. Miller, K. S. Gregg, S. Huprikar, E. D. Lease, A. Zimmer, J. S. Dummer, C. W. Spak, C. Koval, D. B. Banach, M. Shroff, J. Le, D. Ostrander, R. Avery, A. Eid, R. R. Razonable, J. Montero, E. Blumberg, A. Alynbiawi, M. I. Morris, H. B. Randall, G. Alangaden, J. Tessier, T. V. Cacciarelli, M. M. Wagener and H. Y. Sun (2016). “Unique characteristics of cryptococcosis identified after death in patients with liver cirrhosis: Comparison with concurrent cohort diagnosed antemortem.” Med Mycol: 2016 Sep [Epub ahead of print].

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Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of cirrhotic patients with advanced liver disease cryptococcosis was first recognized after death. These patients had the characteristics of presenting with fulminant fungemia, were less likely to have positive serum cryptococcal antigen and posed a diagnostic challenge for care providers.

Shafi, S., S. Barnes, C. Ahn, M. R. Hemilla, H. G. Cryer, A. Nathens, M. Neal and J. Fildes (2016). “Characteristics of acs-verified level i and level ii trauma centers: A study linking trauma center verification review data and the national trauma data bank of the american college of surgeons committee on trauma.” J Trauma Acute Care Surg 81(4): 735-742.

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BACKGROUND: The Trauma Quality Improvement Project of the American College of Surgeons (ACS) has demonstrated variations in trauma center outcomes despite similar verification status. The purpose of this study was to identify structural characteristics of trauma centers that affect patient outcomes. METHODS: Trauma registry data on 361,187 patients treated at 222 ACS-verified Level I and Level II trauma centers were obtained from the National Trauma Data Bank of ACS. These data were used to estimate each center’s observed-to-expected (O-E) mortality ratio with 95% confidence intervals using multivariate logistic regression analysis. De-identified data on structural characteristics of these trauma centers were obtained from the ACS Verification Review Committee. Centers in the lowest quartile of mortality based on O-E ratio (n = 56) were compared to the rest (n = 166) using Classification and Regression Tree (CART) analysis to identify institutional characteristics independently associated with high-performing centers. RESULTS: Of the 72 structural characteristics explored, only 3 were independently associated with high-performing centers: annual patient visits to the emergency department of fewer than 61,000; proportion of patients on Medicare greater than 20%; and continuing medical education for emergency department physician liaison to the trauma program ranging from 55 and 113 hours annually. Each 5% increase in O-E mortality ratio was associated with an increase in total length of stay of one day (r = 0.25; p < 0.001). CONCLUSIONS: Very few structural characteristics of ACS-verified trauma centers are associated with risk-adjusted mortality. Thus, variations in patient outcomes across trauma centers are likely related to variations in clinical practices.

Shafi, S., A. W. Collinsworth, K. M. Richter, H. B. Alam, L. B. Becker, M. R. Bullock, J. M. Ecklund, J. Gallagher, R. Gandhi, E. R. Haut, Z. L. Hickman, H. Hotz, J. McCarthy, A. B. Valadka, J. Weigelt and J. B. Holcomb (2016). “Bundles of care for resuscitation from hemorrhagic shock and severe brain injury in trauma patients-translating knowledge into practice.” J Trauma Acute Care Surg 81(4): 780-794.

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Although clinical practice guidelines for the management of hemorrhagic shock and TBI have been developed and disseminated by multiple organizations, adoption of evidence-based practices at trauma centers remains suboptimal.7,8 In a study of 5 Level I trauma centers, compliance with 22 commonly recommended clinical practices for TBI, hemorrhagic shock, pelvic fractures, and long-bone extremity fractures ranged from 13% to 94%.7 After adjustment for patient demographics and injury severity, each 10% increase in compliance with recommended care was associated with a 14% reduction in risk of death. These findings indicate a gap in knowledge translation.8–10