Prediction of Recurrent Clostridium Difficile Infection Using Comprehensive Electronic Medical Records in an Integrated Healthcare Delivery System.

BACKGROUND Predicting recurrent Clostridium difficile infection (rCDI) remains difficult. METHODS: We employed a retrospective cohort design. Granular electronic medical record (EMR) data had been collected from patients hospitalized at 21 Kaiser Permanente Northern California hospitals. The derivation dataset (2007-2013) included data from 9,386 patients who experienced incident CDI (iCDI) and 1,311 who experienced their first CDI recurrences (rCDI). The validation dataset (2014) included data from 1,865 patients who experienced incident CDI and 144 who experienced rCDI. Using multiple techniques, including machine learning, we evaluated more than 150 potential predictors. Our final analyses evaluated 3 models with varying degrees of complexity and 1 previously published model. RESULTS Despite having a large multicenter cohort and access to granular EMR data (eg, vital signs, and laboratory test results), none of the models discriminated well (c statistics, 0.591-0.605), had good calibration, or had good explanatory power. CONCLUSIONS Our ability to predict rCDI remains limited. Given currently available EMR technology, improvements in prediction will require incorporating new variables because currently available data elements lack adequate explanatory power. Infect Control Hosp Epidemiol 2017;38:1196-1203.

Asthma-related environmental fungus, Alternaria, activates dendritic cells and produces potent Th2 adjuvant activity.

Asthma is thought to result from dysregulated Th2-like airway inflammatory responses to the environment. Although the etiology of asthma is not fully understood in humans, clinical and epidemiological evidence suggest a potential link between exposure to environmental fungi, such as Alternaria, and development and/or exacerbation of asthma. The goal of this project was to investigate the mechanisms of airway Th2 responses by using Alternaria as a clinically relevant model for environmental exposure. Airway exposure of naive animals to an experimental Ag, OVA, or a common allergen, short ragweed pollen, induced no or minimal immune responses to these Ags. In contrast, mice developed strong Th2-like immune responses when they were exposed to these Ags in the presence of Alternaria extract. Extracts of other fungi, such as Aspergillus and Candida, showed similar Th2 adjuvant effects, albeit not as potently. Alternaria stimulated bone marrow-derived dendritic cells (DCs) to express MHC class II and costimulatory molecules, including OX40 ligand, in vitro. Importantly, Alternaria inhibited IL-12 production by activated DCs, and DCs exposed to Alternaria enhanced Th2 polarization of CD4(+) T cells. Furthermore, adoptive airway transfer of DCs, which had been pulsed with OVA in the presence of Alternaria, showed that the recipient mice had enhanced IgE Ab production and Th2-like airway responses to OVA. Thus, the asthma-related environmental fungus Alternaria produces potent Th2-like adjuvant effects in the airways. Such immunogenic properties of certain environmental fungi may explain their strong relationships with human asthma and allergic diseases.