A One Health overview, facilitating advances in comparative medicine and translational research.

TABLE OF CONTENTS: A1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J. BergmanA5 Successful immunotherapy with a recombinant HER2-expressing Listeria monocytogenes in dogs with spontaneous osteosarcoma paves the way for advances in pediatric osteosarcomaNicola J. Mason, Josephine S. Gnanandarajah, Julie B. Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne PatersonA6 Human clinical development of ADXS-HER2Daniel O'ConnorA7 Leveraging use of data for both human and veterinary benefitLaura S. TremlA8 Biologic replacement of the knee: innovations and early clinical resultsJames P. StannardA9 Mizzou BioJoint Center: a translational success storyJames L. CookA10 University and industry translational partnership: from the lab to commercializationMarc JacobsA11 Beyond docking: an evolutionarily guided OneHealth approach to drug discoveryGerald J. Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew SkaffA12 Challenges and opportunities for data applications in animal health: from precision medicine to precision husbandryAmado S. GuloyA13 A cloud-based programmable platform for healthHarlen D. HaysA14 Comparative oncology: One Health in actionAmy K. LeBlancA15 Companion animal diseases bridge the translational gap for human neurodegenerative diseaseJoan R. Coates, Martin L. Katz, Leslie A. Lyons, Gayle C. Johnson, Gary S. Johnson, Dennis P. O'BrienA16 Duchenne muscular dystrophy gene therapyDongsheng DuanA17 Polycystic kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man's best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman.

Associations between Anticholinergic Burden and Adverse Health Outcomes in Parkinson Disease.

BACKGROUND: Elderly adults should avoid medications with anticholinergic effects since they may increase the risk of adverse events, including falls, delirium, and cognitive impairment. However, data on anticholinergic burden are limited in subpopulations, such as individuals with Parkinson disease (PD). The objective of this study was to determine whether anticholinergic burden was associated with adverse outcomes in a PD inpatient population. METHODS: Using the Cerner Health Facts® database, we retrospectively examined anticholinergic medication use, diagnoses, and hospital revisits within a cohort of 16,302 PD inpatients admitted to a Cerner hospital between 2000 and 2011. Anticholinergic burden was computed using the Anticholinergic Risk Scale (ARS). Primary outcomes were associations between ARS score and diagnosis of fracture and delirium. Secondary outcomes included associations between ARS score and 30-day hospital revisits. RESULTS: Many individuals (57.8%) were prescribed non-PD medications with moderate to very strong anticholinergic potential. Individuals with the greatest ARS score (≥ 4) were more likely to be diagnosed with fractures (adjusted odds ratio (AOR): 1.56, 95% CI: 1.29-1.88) and delirium (AOR: 1.61, 95% CI: 1.08-2.40) relative to those with no anticholinergic burden. Similarly, inpatients with the greatest ARS score were more likely to visit the emergency department (adjusted hazard ratio (AHR): 1.32, 95% CI: 1.10-1.58) and be readmitted (AHR: 1.16, 95% CI: 1.01-1.33) within 30-days of discharge. CONCLUSIONS: We found a positive association between increased anticholinergic burden and adverse outcomes among individuals with PD. Additional pharmacovigilance studies are needed to better understand risks associated with anticholinergic medication use in PD.

Outcomes associated with conventional versus lipid-based formulations of amphotericin B in propensity-matched groups.

BACKGROUND: Lipid-based formulations of amphotericin B (LF-AMB) are indicated for treatment of invasive fungal infections in patients intolerant to conventional amphotericin B (CAB) or with refractory infections. Physicians still may choose to administer CAB to such patients. We described the use of CAB and LF-AMB in this population and quantified differences in post-amphotericin B length of stay (LOS) among survivors and hospital mortality in matched patients. METHODS: Data were extracted from Health Facts (Cerner Corporation, Kansas City, MO, USA) for a retrospective cohort analysis. Inpatients aged ≥18 years with evidence of fungal infection and with orders for LF-AMB or CAB on ≥2 days from January 2001 to June 2010 were identified. Patients were required to have renal insufficiency or other relative contraindications to use of CAB, exposure to nephrotoxic agents, or evidence of a CAB-refractory infection. Multilevel (hierarchical) mixed-effects logistic regression was used to determine factors associated with initial exposure to LF-AMB versus CAB. Multivariate adjustment of outcomes was done using propensity score matching. RESULTS: 655 patients were identified: 322 patients initiated therapy with CAB and 333 initiated treatment with LF-AMB. Compared to those initiating CAB, patients initiating LF-AMB had greater acuity and underlying disease severity. In unadjusted analyses, hospital mortality was significantly higher in the LF-AMB group (32.2% versus 23.7%; P = 0.02). After propensity score matching and covariate adjustment, mortality equalized and observed differences in LOS after amphotericin B initiation decreased. CONCLUSION: Among patients at risk for amphotericin B toxicity, differences between CAB and LF-AMB seen in crude outcomes analyses relate to channeling of sicker patients to initiate treatment with LF-AMB. Failing to account for differences among patients that drive clinical decision-making will result in inaccurate conclusions about the real-world effectiveness of different amphotericin B formulations.

Development and validation of a bedside risk score for MRSA among patients hospitalized with complicated skin and skin structure infections.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of complicated skin and skin structure infections (cSSSI). Patients with MRSA require different empiric treatment than those with non-MRSA infections, yet no accurate tools exist to aid in stratifying the risk for a MRSA cSSSI. We sought to develop a simple bedside decision rule to tailor empiric coverage more accurately. METHODS: We conducted a large multicenter (N=62 hospitals) retrospective cohort study in a US-based database between April 2005 and March 2009. All adult initial admissions with ICD-9-CM codes specific to cSSSI were included. Patients admitted with MRSA vs. non-MRSA were compared with regard to baseline demographic, clinical and hospital characteristics. We developed and validated a model to predict the risk of MRSA, and compared its performance via sensitivity, specificity and other classification statistics to the healthcare-associated (HCA) infection risk factors. RESULTS: Of the 7,183 patients with cSSSI, 2,387 (33.2%) had MRSA. Factors discriminating MRSA from non-MRSA were age, African-American race, no evidence of diabetes mellitus, cancer or renal dysfunction, and prior history of cardiac dysrhythmia. The score ranging from 0 to 8 points exhibited a consistent dose-response relationship. A MRSA score of 5 or higher was superior to the HCA classification in all characteristics, while that of 4 or higher was superior on all metrics except specificity. CONCLUSIONS: MRSA is present in 1/3 of all hospitalized cSSSI. A simple bedside risk score can help discriminate the risk for MRSA vs. other pathogens with improved accuracy compared to the HCA definition.

Treatment of candidemia with echinocandins: data on hospital resource use from a real world setting.

OBJECTIVE: Real-world data on patients treated with echinocandins for candidemia are limited. This study examined the effect of three echinocandin-based treatment regimens on resource utilization in patients with Candida infection. RESEARCH DESIGN AND METHODS: A retrospective cohort study of patients hospitalized between 2005 and 2010 with a blood culture positive for Candida. Length of stay (LOS) following AF initiation (post-AF LOS) and total days with AF treatment were compared in patients treated with three different echinocandin regimens: patients with echinocandin only, patients who received fluconazole prior to an echinocandin (fluconazole-echinocandin), and patients who received an echinocandin prior to fluconazole (echinocandin-fluconazole). Generalized linear models were used to adjust for confounders. RESULTS: A total of 647 patients met inclusion criteria. Patients treated with echinocandin only were more acutely ill, having more organ dysfunction and sepsis. Unadjusted post-AF LOS was significantly greater in the groups that received both echinocandin and fluconazole (mean, 13.1 days for echinocandin-only vs 25.5 and 21.2 days for fluconazole-echinocandin and echinocandin-fluconazole groups, respectively, p<0.001). These groups also had a higher total number of days with AF orders. These differences remained after multivariate adjustment and in survivor-only analyses. Compared with echinocandin-only treatment, the average marginal effect of fluconazole-echinocandin and echinocandin-fluconazole regimens were associated with significantly longer adjusted post-AF LOS (by 7.2 days and 9.3 days, respectively, p<0.001) and significantly more adjusted total AF days (by 5.3 days for fluconazole-echinocandin and 6.5 days for echinocandin-fluconazole patients, p<0.001). Limitations included lack of visibility to specific reasons for therapy changes. CONCLUSIONS: Fluconazole before or after echinocandin was associated with significantly greater resource utilization than echinocandin use alone.