Delirium is a Strong Predictor of Mortality in Patients Receiving Non-invasive Positive Pressure Ventilation.

PURPOSE: Non-invasive positive pressure ventilation (NIPPV) has gained popularity over the years in the treatment of acute respiratory failure (ARF). Preliminary evidence suggests that delirium is an important factor contributing to NIPPV failure and death. This study was conducted to evaluate delirium and other associated factors of deaths in patients with ARF requiring the use of NIPPV. METHODS: A prospective observational study was conducted in a specialised NIPPV unit. Consecutive patients admitted for ARF requiring NIPPV were assessed by a psychiatrist for presence of delirium using the Diagnostic and Statistical Manual Version IV (DSM-IV). APACHE II score, co-morbidities-, and lung function were also assessed. Patients were followed until their deaths for a minimum of 1 year. Univariate and multivariate Cox's regression analyses were performed to explore predictive factors for death. RESULTS: A total of 153 subjects were recruited, 49 (32.0 %) of whom had delirium. On univariate analysis, higher APACHE II score, lower BMI, presence of delirium, higher Charlson's co-morbidity index but not FEV1 were associated with earlier death. On multivariate analysis, delirium (HR 4.4; 95 % CI 2.6-7.4; p < 0.001) and lower BMI (HR 0.92; 95 % CI 0.86-0.98; p = 0.013) were independently associated with earlier death within 1 year. CONCLUSIONS: There is a high prevalence of delirium in patients requiring NIPPV. The presence of delirium is a strong predictor of mortality. There is strong need to identify and manage these high-risk patients to improve their mortality. The collaboration between psychiatrists and physicians should be strengthened.

Investigation of antibacterial mode of action for traditional and amphiphilic aminoglycosides.

Aminoglycoside represents a class of versatile and broad spectrum antibacterial agents. In an effort to revive the antibacterial activity against aminoglycoside resistant bacteria, our laboratory has developed two new classes of aminoglycoside, pyranmycin and amphiphilic neomycin (NEOF004). The former resembles the traditional aminoglycoside, neomycin. The latter, albeit derived from neomycin, appears to exert antibacterial action via a different mode of action. In order to discern that these aminoglycoside derivatives have distinct antibacterial mode of action, RNA-binding affinity and fluorogenic dye were employed. These studies, together with our previous investigation, confirm that pyranmycin exhibit the traditional antibacterial mode of action of aminoglycosides by binding toward the bacterial rRNA. On the other hand, the amphiphilic neomycin, NEOF004 disrupts the bacterial cell wall. In a broader perspective, it verifies that structurally modified neomycin can exert different antibacterial mode of action leading to the revival of activity against aminoglycoside resistant bacteria.

Mode of action investigation for the antibacterial cationic anthraquinone analogs.

Reported previously by our group, we have developed a novel class of antibacterial cationic anthraquinone analogs with superb potency (MIC <1µg/mL) against Gram positive (G+) pathogens including Methicillin-resistant Staphylococcus aureus (MRSA). However, most of these compounds only manifest modest antibacterial activity against Gram negative (G-) bacteria. Further investigation on the antibacterial mode of action using fluorogenic dyes reveals that these compounds exert two different modes of action that account for the difference in their antibacterial profile. It was found that most of the compounds exert their antibacterial activity by disrupting the redox processes of bacteria. At high concentration, these compounds can also act as membrane disrupting agents. This information can help to design new therapeutics against various bacteria.

Synthesis and antibacterial activity study of a novel class of cationic anthraquinone analogs.

Reported previously by our group, one-pot cycloaddition using naphthoquinone, sodium azide and alkyl halides can lead to the formation of both 1-alkyl-1H- and 2-alkyl-2H-naphtho[2,3-d]triazole-4,9-diones. Herein, the effect of leaving group and additive in dictating the selectivity between the formation of 1-alkyl-1H- and 2-alkyl-2H-naphtho[2,3-d]triazole-4,9-diones has been further investigated. In the process of investigating the factors that control the selectivity and the biological activity associated with these two compounds, a novel class of antibacterial cationic anthraquinone analogs has been developed. Although these compounds are structurally similar, different antibacterial profiles are noted. One lead compound, 4e manifests high potency (MIC<1µg/mL) and selectivity against Gram positive (G+) pathogens including methicillin-resistant Staphylococcus aureus (MRSA) while exerting only modest activity against Gram negative (G-) bacteria. Other lead compounds (4f and 4g) exhibit broad antibacterial activity including MRSA and vancomycin-resistant Enterococcus faecalis (VRE) that is comparable to other commercially available cationic antiseptic chemicals. This unique difference in antibacterial profile may pave the way for the development of new therapeutic agents.

Health priorities among women recently released from jail.

OBJECTIVE: To describe the health priorities of women recently released from jail. METHOD: We open-coded semi-structured interview transcripts collected from 28 women within 6 months after their release from jail to identify themes associated with prioritization of health. RESULTS: Five out of 28 women listed health as their top post-release priority. However, many women had competing priorities after release, including housing, employment, and children. We found that women described several reasons why health was not a priority; however, participants reported regular use of the healthcare system upon release from jail, indicating that health was important to them to some degree. CONCLUSIONS: Our findings from may inform intervention efforts that connect women to healthcare resources and increase health-promoting behavior during the transition from jail to community.

Library synthesis and antibacterial investigation of cationic anthraquinone analogs.

We report the parallel synthesis of a series of novel 4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-3-ium chloride salts, which are analogs to cationic anthraquinones. Three synthetic protocols were examined leading to a convenient and facile library synthesis of the cationic anthraquinone analogs that contain double alkyl chains of various lengths (C(2)-C(12)) at N-1 and N-3 positions. The antibacterial activities of these compounds were evaluated against Gram-positive bacterium Staphylococcus aureus and Gram-negative bacterium Escherichia coli. The antibacterial activities of these compounds were expected to be associated with the structural features of naphthoquinone, cation and lypophilic alkyl chain and, interestingly, they showed much higher levels of antibacterial activities against G+ than G- bacteria. In addition, when the total number of carbon atoms of the alkyl groups at both N-1 and N-3 positions lies between 9 and 18, the bactericidal activity against S. aureus increased with increasing alkyl chain length at both N-atoms with MIC ≤ 1 µg/mL.