Vascular access complications during outpatient parenteral antimicrobial therapy at home: a retrospective cohort study.

OBJECTIVES: The need for indwelling vascular access for outpatient parenteral antimicrobial therapy (OPAT) places patients at risk of vascular access complications. The purpose of this study was to describe vascular access complications during OPAT at home, and identify factors associated with their occurrence. METHODS: All OPAT courses carried out at home for patients at Cleveland Clinic in 2013 were identified from the institution's OPAT registry. The first OPAT course per patient was included. Vascular access complications that occurred during the treatment course were abstracted from the electronic medical record. Only complications that triggered a clinical intervention were included. RESULTS: The 1461 included OPAT courses encompassed 33,579 OPAT days of treatment. One-hundred-and-forty-four vascular access complications occurred in 131 OPAT courses (9% of OPAT courses, 4.29 complications per 1000 OPAT days). The most common complication was occlusion (53% of all complications). Hickman catheters [incidence rate ratio (IRR) 0.20, 95% CI 0.03-0.63] and indwelling ports (IRR 0.25, 95% CI 0.04-0.78) were associated with lower complication rates than peripherally inserted central catheters, as was increasing age (IRR 0.99, 95% CI 0.98-1.00). Log OPAT duration (IRR 1.60, 95% CI 1.28-2.03), female sex (IRR 1.62, 95% CI 1.16-2.28) and injection drug use (IRR 3.32, 1.16-7.46) were associated with increased risk of vascular access complications. CONCLUSIONS: Nine percent of OPAT courses at home have at least one vascular access complication requiring clinical intervention. Longer OPAT duration, younger age, female sex and injection drug use are associated with increased risk of vascular access complications.

Solution structure of a conserved domain of antizyme: a protein regulator of polyamines.

Antizyme and its isoforms are members of an unusual yet broadly conserved family of proteins, with roles in regulating polyamine levels within cells. Antizyme has the ability to bind and inhibit the enzyme ornithine decarboxylase (ODC), targeting it for degradation at the proteasome; antizyme is also known to affect the transport of polyamines and interact with the antizyme inhibitor protein (AZI), as well as the cell-cycle protein cyclin D1. In the present work, NMR methods were used to determine the solution structure of a stable, folded domain of mammalian antizyme isoform-1 (AZ-1), consisting of amino acid residues 87-227. The protein was found to contain eight beta strands and two alpha helices, with the strands forming a mixed parallel and antiparallel beta sheet. At the level of primary sequence, antizyme is not similar to any protein of known structure, and results show that antizyme exhibits a novel arrangement of its strands and helices. Interestingly, however, the fold of antizyme is similar to that found in a family of acetyl transferases, as well as translation initiation factor IF3, despite a lack of functional relatedness between these proteins. Structural results, combined with amino acid sequence comparisons, were used to identify conserved features among the various homologues of antizyme and their isoforms. Conserved surface residues, including a cluster of acidic amino acids, were found to be located on a single face of antizyme, suggesting this surface is a possible site of interaction with target proteins such as ODC. This structural model provides an essential framework for an improved future understanding of how the different parts of antizyme play their roles in polyamine regulation.