17 research outputs found
Inhibition of Virulence Factor Expression and Phage-Induced Lysis by Nitric Oxide in Escherichia coli O157:H7
No full textOur research uses computational and experimental methodologies in systems biology to address limitations of traditional antimicrobials. Traditional antimicrobials can cause phage-induced bacterial lysis, virulence factor expression, and extracellular protein release in Escherichia coli O157:H7 and are thus contraindicated for treatment. Previous research has demonstrated that nitric oxide (NO¿), an effector of microbial cytotoxicity by macrophages, inhibits Stx2 expression in E. coli O157:H7 (SHIMIZU et al. 2012; VAREILLE et al. 2007). Because of this, we hypothesized that NO¿ may be able to reduce virulence factor expression and phage-induced lysis. We constructed fluorescent reporter plasmids of the promoter activities of three representative virulence factors ¿ stx1, stx2, and katP, as well as sulA as a positive control. DNA damaging agents normally induce these genes concurrently with lysis. Except for KatP, we found that treatment with a NO¿ donor quenched DNA-damage induced expression of these genes in a global effect, and further investigation using KCN, a respiration inhibitor and chloramphenicol, a translation inhibitor, indicated that NO¿ is interfering with translation to cause this inhibitory effect. Furthermore, we also observed that NO¿ inhibits phage-induced lysis and extracellular protein release upon co-treatment with mitomycin C, ofloxacin, and hydrogen peroxide (H2O2). Additionally, we developed a preliminary NO¿ kinetic model in E. coli O157:H7 from a previous model in E. coli K-12 (ROBINSON and BRYNILDSEN 2013), which identified iron-sulfur cluster [Fe-S] damage as a potential mechanism for translation inhibition. This indicates that increasing NO¿ concentration in bacterial cells is a viable strategy for future research addressing the clinical problem of antimicrobial induced virulence factor expression and phage-induced lysis in E. coli O157:H7
International Analgesia, Sedation, and Delirium Practices: a prospective cohort study
No full textAbstract Background While understanding of critical illness and delirium continue to evolve, the impact on clinical practice is often unknown and delayed. Our purpose was to provide insight into practice changes by characterizing analgesia and sedation usage and occurrence of delirium in different years and international regions. Methods We performed a retrospective analysis of two multicenter, international, prospective cohort studies. Mechanically ventilated adults were followed for up to 28 days in 2010 and 2016. Proportion of days utilizing sedation, analgesia, and performance of a spontaneous awakening trial (SAT), and occurrence of delirium were described for each year and region and compared between years. Results A total of 14,281 patients from 6 international regions were analyzed. Proportion of days utilizing analgesia and sedation increased from 2010 to 2016 (p < 0.001 for each). Benzodiazepine use decreased in every region but remained the most common sedative in Africa, Asia, and Latin America. Performance of SATs increased overall, driven mostly by the US/Canada region (24 to 35% of days with sedation, p < 0.001). Any delirium during admission increased from 7 to 8% of patients overall and doubled in the US/Canada region (17 to 36%, p < 0.001). Conclusions Analgesia and sedation practices varied widely across international regions and significantly changed over time. Opportunities for improvement in care include increasing delirium monitoring, performing SATs, and decreasing use of sedation, particularly benzodiazepines
Multicenter International Cohort Validation of a Modified Sequential Organ Failure Assessment Score Using the Richmond Agitation-Sedation Scale
No full textOBJECTIVE: In a multicenter, international cohort, we aimed to validate a modified Sequential Organ Failure Assessment (mSOFA) using the Richmond Agitation-Sedation Scale, hypothesized as comparable to the Glasgow Coma Scale (GCS)-based Sequential Organ Failure Assessment
(SOFA).
SUMMARY BACKGROUND DATA: The SOFA score, whose neurologic component is based on the GCS, can predict ICU mortality. But, GCS is often missing in lieu of other assessments, such as the also reliable and validated RASS. Single center data suggested a RASS-based SOFA (mSOFA) predicted ICU mortality.
METHODS: Our nested cohort within the prospective 2016 Fourth International Study of Mechanical Ventilation contains 4,120 ventilated patients with daily RASS and GCS assessments (20,023 patient-days, 32 countries). We estimated GCS from RASS via a proportional odds
model without adjustment. ICU mortality logistic regression models and c-statistics were constructed using SOFA (measured GCS) and mSOFA (measured RASS-estimated GCS), adjusted for age, sex, body-mass index, region (Europe, USA-Canada, Latin America, Africa, Asia, Australia-
New Zealand), and post-operative status (medical/surgical).
RESULTS: Cohort-wide, the mean SOFA=9.4+/-2.8 and mean mSOFA=10.0+/-2.3, with ICU mortality=31%. Mean SOFA and mSOFA similarly predicted ICU mortality (SOFA: AUC=0.784, 95%CI=0.769-0.799; mSOFA: AUC=0.778, 95%CI=0.763-0.793, P=0.139). Across models, other predictors of mortality included higher age, female sex, medical patient, and African region (all P< 0.001).
CONCLUSIONS: We present the first SOFA modification with RASS in a “real-world” international cohort. Estimating GCS from RASS preserves predictive validity of SOFA to predict ICU mortality. Alternative neurologic measurements like RASS can be viably integrated into severity of illness scoring systems like SOFA
The association between the public reporting of individual operator outcomes with patient profiles, procedural management, and mortality after percutaneous coronary intervention: an observational study from the Pan-London PCI (BCIS) Registry using an interrupted time series analysis.
No full textThis is a pre-copyedited, author-produced version of an article accepted for publication in European Heart Journal,, following peer review. The version of record: Daniel A Jones, Krishnaraj S Rathod, Sudheer Koganti, Pitt Lim, Sam Firoozi, Richard Bogle, Ajay K Jain, Philip A MacCarthy, Miles C Dalby, Iqbal S Malik, Anthony Mathur, Ranil DeSilva, Roby Rakhit, Sundeep Singh Kalra, Simon Redwood, Peter Ludman, Andrew Wragg, The association between the public reporting of individual operator outcomes with patient profiles, procedural management, and mortality after percutaneous coronary intervention: an observational study from the Pan-London PCI (BCIS) Registry using an interrupted time series analysis, European Heart Journal, Volume 40, Issue 31, 14 August 2019, Pages 2620–2629 is available online at: https://doi.org/10.1093/eurheartj/ehz152AIMS: The public reporting of healthcare outcomes has a number of potential benefits; however, unintended consequences may limit its effectiveness as a quality improvement process. We aimed to assess whether the introduction of individual operator specific outcome reporting after percutaneous coronary intervention (PCI) in the UK was associated with a change in patient risk factor profiles, procedural management, or 30-day mortality outcomes in a large cohort of consecutive patients. METHODS AND RESULTS: This was an observational cohort study of 123 780 consecutive PCI procedures from the Pan-London (UK) PCI registry, from January 2005 to December 2015. Outcomes were compared pre- (2005-11) and post- (2011-15) public reporting including the use of an interrupted time series analysis. Patients treated after public reporting was introduced were older and had more complex medical problems. Despite this, reported in-hospital major adverse cardiovascular and cerebrovascular events rates were significantly lower after the introduction of public reporting (2.3 vs. 2.7%, P < 0.0001). Interrupted time series analysis demonstrated evidence of a reduction in 30-day mortality rates after the introduction of public reporting, which was over and above the existing trend in mortality before the introduction of public outcome reporting (35% decrease relative risk 0.64, 95% confidence interval 0.55-0.77; P < 0.0001). CONCLUSION: The introduction of public reporting has been associated with an improvement in outcomes after PCI in this data set, without evidence of risk-averse behaviour. However, the lower reported complication rates might suggest a change in operator behaviour and decision-making confirming the need for continued surveillance of the impact of public reporting on outcomes and operator behaviour
Antimicrobial exposure and the risk of delirium in critically ill patients
No full textAbstract Background Prior retrospective cross-sectional work has associated antimicrobials with a non-specific phrase: encephalopathy without seizures. The purpose of this study is to determine whether different classes of antimicrobials have differential associations with the daily risk of delirium after critical illness is adjusted for. Methods Our study was a nested cohort that enrolled non-neurological critically ill adults from a medical or surgical intensive care unit (ICU) with daily follow-up to 30 days. Our independent variable was exposure to previous-day antimicrobial class: beta-lactams (subclasses: penicillins, first- to third-generation cephalosporins, fourth-generation cephalosporins, and carbapenems), macrolides, fluoroquinolones, and other. We adjusted for baseline covariates (age, comorbidities, cognition scores, sepsis, and mechanical ventilation), previous-day covariates (delirium, doses of analgesics/sedatives, and antipsychotic use), and same-day covariates (illness severity). Our primary outcome of delirium was measured by using the Confusion Assessment Method for the ICU. A daily delirium logistic regression model was used with an ICU time-restricted sensitivity analysis including daily adjustment for sepsis and mechanical ventilation. Results Of 418 ICU patients, delirium occurred in 308 (74%) with a median of 3 days (interquartile range 2–6) among those affected and 318 (76%) were exposed to antimicrobials. When covariates and ICU type were adjusted for, only first- to third-generation cephalosporins were associated with delirium (logistic regression model odds ratio (OR) = 2.2, 95% confidence interval (CI) 1.28–3.79, P = 0.004; sensitivity analysis OR = 2.13, 95% CI 1.10–4.10, P = 0.024). Conclusions First-, second-, and third-generation cephalosporins doubled the odds of delirium after baseline co-morbidities, ICU type, the course of critical care, and other competing antimicrobial and psychotropic medication risks were adjusted for. We did not find an association between delirium and cefepime, penicillins, carbapenems, fluoroquinolones, or macrolides
Additional file 1: of Antimicrobial exposure and the risk of delirium in critically ill patients
No full textTable S1. Antimicrobial agents used in the critically ill cohort (organized by major class and frequency). Table S2. Delirium risk after antimicrobial exposure using a logistic regression model with cluster sandwich covariance estimator restricted to intensive care unit (ICU) days. (DOCX 46 kb
