Characteristics, clinical course, and outcomes of homeless and non-homeless patients admitted to ICU: A retrospective cohort study.

BACKGROUND: Little is known about homeless patients in intensive care units (ICUs). OBJECTIVES: To compare clinical characteristics, treatments, and outcomes of homeless to non-homeless patients admitted to four ICUs in a large inner-city academic hospital. METHODS: 63 randomly-selected homeless compared to 63 age-, sex-, and admitting-ICU-matched non-homeless patients. RESULTS: Compared to matched non-homeless, homeless patients (average age 48±12 years, 90% male, 87% admitted by ambulance, 56% mechanically ventilated, average APACHE II 17) had similar comorbidities and illness severity except for increased alcohol (70% vs 17%,p<0.001) and illicit drug(46% vs 8%,p<0.001) use and less documented hypertension (16% vs 40%,p = 0.005) or prescription medications (48% vs 67%,p<0.05). Intensity of ICU interventions was similar except for higher thiamine (71% vs 21%,p<0.0001) and nicotine (38% vs 14%,p = 0.004) prescriptions. Homeless patients exhibited significantly lower Glasgow Coma Scores and significantly more bacterial respiratory cultures. Longer durations of antibiotics, vasopressors/inotropes, ventilation, ICU and hospital lengths of stay were not statistically different, but homeless patients had higher hospital mortality (29% vs 8%,p = 0.005). Review of all deaths disclosed that withdrawal of life-sustaining therapy occurred in similar clinical circumstances and proportions in both groups, regardless of family involvement. Using multivariable logistic regression, homelessness did not appear to be an independent predictor of hospital mortality. CONCLUSIONS: Homeless patients, admitted to ICU matched to non-homeless patients by age and sex (characteristics most commonly used by clinicians), have higher hospital mortality despite similar comorbidities and illness severity. Trends to longer durations of life supports may have contributed to the higher mortality. Additional research is required to validate this higher mortality and develop strategies to improve outcomes in this vulnerable population.

Development of a zebrafish sepsis model for high-throughput drug discovery.

Sepsis is a leading cause of death worldwide. Current treatment modalities remain largely supportive. Intervention strategies focused on inhibiting specific mediators of the inflammatory host response have been largely unsuccessful, a consequence of an inadequate understanding of the complexity and heterogeneity of the innate immune response. Moreover, the conventional drug development pipeline is time consuming and expensive and the low success rates associated with cell-based screens underline the need for whole organism screening strategies, especially for complex pathological processes. Here, we established an LPS-induced zebrafish endotoxemia model, which exhibits the major hallmarks of human sepsis including, edema and tissue/organ damage, increased vascular permeability and vascular leakage accompanied by an altered expression of cellular junction proteins, increased cytokine expression, immune cell activation and ROS production, reduced circulation and increased platelet aggregation. We tested the suitability of the model for phenotype-based drug screening using three primary readouts: mortality, vascular leakage, and ROS production. Preliminary screening identified fasudil, a drug known to protect against vascular leakage in murine models, as a lead hit thereby validating the utility of our model for sepsis drug screens. This zebrafish sepsis model has the potential to rapidly analyze sepsis associated pathologies and cellular processes in the whole organism, as well as to screen and validate large numbers of compounds that can modify sepsis pathology in vivo.