Assessing predictive accuracy for outcomes of ventilator-associated events in an international cohort: the EUVAE study

Purpose

To analyze the impact on patient outcome of ventilator-associated events (VAEs) as defined by the Centers for Disease Control and Prevention (CDC) in 2008, 2013, and the correlation with ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT).

Methods

This was a prospective, observational, multicenter, international study conducted at 13 intensive care units (ICUs); thirty consecutive adults mechanically ventilated for ≥?48 h per site were eligible, with daily follow-up being recorded in a collaborative web database; VAEs were assessed using the 2013 CDC classification and its 2015 update.

Results

A total of 2856 ventilator days in 244 patients were analyzed, identifying 33 VAP and 51 VAT episodes; 30-day ICU mortality was significantly higher (42.8 vs. 19.6%, p?<?0.007) in patients with VAP than in those with VAT. According to the 2013 CDC definitions, 117 VAEs were identified: 113 (96%) were infection-related ventilator-associated complication-plus (IVAC-plus), while possible ventilator-associated pneumonia (PVAP) was found in 64 (56.6%) of them. VAE increased the number of ventilator days and prolonged ICU and hospital LOS (by 5, 11, and 12 days, respectively), with a trend towards increased 30-day mortality (43 vs 28%, p?=?0.06). Most episodes (26, 55%) classified as IVAC-plus without PVAP criteria were due to atelectasis. PVAP significantly increased (p?<?0.05) ventilator days as well as ICU and hospital LOS (by 10.5, 14, and 13 days, respectively). Only 24 (72.7%) of VAP and 15 (29.4%) of VAT episodes met IVAC-plus criteria.

Conclusions

Respiratory infections (mainly VAT) were the most common complication. VAE algorithms only identified events with surrogates of severe oxygenation deterioration. As a consequence, IVAC definitions missed one fourth of the episodes of VAP and three fourths of the episodes of VAT. Identifying VAT (often missed by IVAC-plus criteria) is important, as VAP and VAT have different impacts on mortality.

     

Antimicrobial susceptibility patterns of Streptococcus pneumoniae in Mexico

The susceptibility to 14 beta-lactam and non-beta-lactam antimicrobial agents was evaluated for Streptococcus pneumoniae from patients with community-acquired respiratory infections in a Mexican medical center. Three hundred fifteen pneumococcal isolates obtained from patients between 1995 and 2001 were tested by the broth microdilution test. Fifty-two percent of the isolates were nonsusceptible to penicillin (minimal inhibitory concentration, >0.06 microg/mL). Penicillin-nonsusceptible isolates were more likely to exhibit resistance to cephalosporins, macrolides, ciprofloxacin, trimethoprim/sulfamethoxazole, chloramphenicol, and tetracycline when compared to penicillin-susceptible isolates. Ninety-three percent of the penicillin-nonsusceptible isolates were resistant to at least one other class of antimicrobials, in contrast to only 47% of the penicillin-susceptible strains (p < 0.0001). More than 90% of the tested isolates were susceptible to amoxicillin/clavulanate, ceftriaxone, levofloxacin, and gatifloxacin. Reduced susceptibility to penicillin was considered to be a reliable marker for the higher probability of multidrug resistance, thus requiring in vitro tests to guide chemotherapy or the choices of parenteral extended spectrum cephalosporins or newer respiratory quinolones.     

Surface-modified silica nanoparticles for tumor-targeted delivery of camptothecin and its biological evaluation

Here we report the design, synthesis and biological evaluation of surface-modified silica nanoparticles (SNP) for the delivery of camptothecin (CPT). Drug has been covalently linked to the nanoparticle through an ester bond with the 20-hydroxy moiety, in order to stabilize its lactone ring and to avoid unspecific release of the drug. The obtained material is highly stable in plasma, with low release of the cargo at physiological pH. Cell internalization and in vitro efficacy assays demonstrated that nanoparticles carrying CPT (SNP-CPT) entered cells via endocytosis and the intracellular release of the cargo induced cell death with half maximal inhibitory concentration (IC₅₀) values and cell cycle distribution profiles similar to those observed for the naked drug. Further, in vivo biodistribution, therapeutic efficacy and biocompatibility of the SNP-CPT were evaluated in human colorectal cancer xenografts using in vivo fluorescence or bioluminescence optical imaging. In vivo tumor-accumulation and whole-body tissue distribution were carried out based on the acquisition of fluorescence emission of a fluorophore (Cy5.5) conjugated to the SNP-CPT, as well as by HPLC quantification of tissue CPT levels. The results showed that, although SNP-CPT tended to accumulate in organs of the reticulo-endothelial system, nanoparticles boost CPT concentration in tumor vs administration of the free drug. Accordingly, SNP-CPT treatment delayed the growth of subcutaneous tumors while significantly reducing the systemic toxicity associated with CPT administration. These results indicate that the SNP-CPT could be used as a robust drug delivery system for antitumoral treatments based on CPT.     

Prevalence, persistence, and microbiology of Staphylococcus aureus nasal carriage among hemodialysis outpatients at a major New York Hospital

The study aimed to determine the natural history of Staphylococcus aureus nasal colonization in hemodialysis outpatients. Surveillance cultures were taken from patients presenting for hemodialysis or routine care to identify S. aureus nasal carriers. A prospective cohort study was performed to identify risks for persistent colonization. Detailed microbiologic and molecular studies of colonizing isolates were performed. Only 23/145 (15.9%) dialysis patients were persistently colonized, and only HIV-positive status was associated with persistence (P = 0.05). Prior hospitalization was the only risk factor for methicillin-resistant S. aureus carriage (OR 2.5, P = 0.03). In isolates from patients with ≤ 42 days of vancomycin exposure, vancomycin minimum bactericidal concentrations (MBCs) increased with duration of exposure. Among dialysis patients, S. aureus colonization was limited and transient; only HIV status was associated with persistence. Nevertheless, duration of vancomycin exposure was associated with increasing vancomycin MBCs. Vancomycin exposure in S. aureus carriers may be involved in increasing resistance.     

Dynamic risk groups among adult male sexual offenders

In the present study, the 16-item Stable-2000 was used to identify different dynamic risk groups among 419 adult male sexual offenders who were referred for assessments between 2000 and 2007. Using a two-stage cluster analysis, four dynamic risk groups were identified: (a) a low needs group who scored below the overall sample mean on all of the Stable-2000 items; (b) a typical group who had intermediate scores on many items; (c) a sexually deviant group who scored relatively high on deviant sexual interests, sexual preoccupation, emotional identification with children, and child molester attitudes; and (d) a pervasive high-needs group who scored relatively high on many Stable-2000 items, reflecting a variety of problems in both general and sexual self-regulation. These dynamic risk groups were not redundant with offender type based on victim age, relatedness, or gender, and did not differ in terms of age at time of assessment, marital status, number of sexual victims, or long-term risk, estimated using the Static-99. The implications for treating and supervising sexual offenders with different dynamic risk profiles are discussed.     

Student nurses and the electronic medical record: a partnership of academia and healthcare

The advent of the electronic medical record has brought a new challenge to nursing education. Although most nursing students are proficient in data entry and computer skills, they often do not comprehend how the information they enter becomes a vital component of interdisciplinary team communication. Furthermore, the electronic medical record becomes a repository for information that can be retrieved for the purpose of decision support. Developed by the Cleveland Clinic, the Deans' Roundtable, and University Hospitals of Cleveland, the Student Nurse Portal provides a means of assisting the student to understand how data entered into the computer transforms into information and knowledge, resulting in the wisdom that enables healthcare workers to provide optimal patient care. Current courses present the purpose of the electronic medical record and its roleas a powerful communication tool, but future courses will also help the student develop data entry and retrieval skills. Hosted on the Cleveland Clinic servers and available to students around-the-clock from any computer with Internet access, students have found the Student Nurse Portal to be a valuable tool in preparing for the use of the electronic medical record during their clinical experiences.     

Action of Obestatin in Skeletal Muscle Repair: Stem Cell Expansion,Muscle Growth,and Microenvironment Remodeling

The development of therapeutic strategies for skeletal muscle diseases, such as physical injuries and myopathies, depends on the knowledge of regulatory signals that control the myogenic process. The obestatin/GPR39 system operates as an autocrine signal in the regulation of skeletal myogenesis. Using a mouse model of skeletal muscle regeneration after injury and several cellular strategies, we explored the potential use of obestatin as a therapeutic agent for the treatment of trauma-induced muscle injuries. Our results evidenced that the overexpression of the preproghrelin, and thus obestatin, and GPR39 in skeletal muscle increased regeneration after muscle injury. More importantly, the intramuscular injection of obestatin significantly enhanced muscle regeneration by simulating satellite stem cell expansion as well as myofiber hypertrophy through a kinase hierarchy. Added to the myogenic action, the obestatin administration resulted in an increased expression of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) and the consequent microvascularization, with no effect on collagen deposition in skeletal muscle. Furthermore, the potential inhibition of myostatin during obestatin treatment might contribute to its myogenic action improving muscle growth and regeneration. Overall, our data demonstrate successful improvement of muscle regeneration, indicating obestatin is a potential therapeutic agent for skeletal muscle injury and would benefit other myopathies related to muscle regeneration.