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1.  Development and validation of immune dysfunction score to predict 28-day mortality of sepsis patients 
PLoS ONE  2017;12(10):e0187088.
Background
Sepsis-induced immune dysfunction ranging from cytokines storm to immunoparalysis impacts outcomes. Monitoring immune dysfunction enables better risk stratification and mortality prediction and is mandatory before widely application of immunoadjuvant therapies. We aimed to develop and validate a scoring system according to patients’ immune dysfunction status for 28-day mortality prediction.
Methods
A prospective observational study from a cohort of adult sepsis patients admitted to ICU between August 2013 and June 2016 at Kaohsiung Chang Gung Memorial Hospital in Taiwan. We evaluated immune dysfunction status through measurement of baseline plasma Cytokine levels, Monocyte human leukocyte-DR expression by flow cytometry, and stimulated immune response using post LPS stimulated cytokine elevation ratio. An immune dysfunction score was created for 28-day mortality prediction and was validated.
Results
A total of 151 patients were enrolled. Data of the first consecutive 106 septic patients comprised the training cohort, and of other 45 patients comprised the validation cohort. Among the 106 patients, 21 died and 85 were still alive on day 28 after ICU admission. (mortality rate, 19.8%). Independent predictive factors revealed via multivariate logistic regression analysis included segmented neutrophil-to-monocyte ratio, granulocyte-colony stimulating factor, interleukin-10, and monocyte human leukocyte antigen-antigen D–related levels, all of which were selected to construct the score, which predicted 28-day mortality with area under the curve of 0.853 and 0.789 in the training and validation cohorts, respectively.
Conclusions
The immune dysfunction scoring system developed here included plasma granulocyte-colony stimulating factor level, interleukin-10 level, serum segmented neutrophil-to-monocyte ratio, and monocyte human leukocyte antigen-antigen D–related expression appears valid and reproducible for predicting 28-day mortality.
doi:10.1371/journal.pone.0187088
PMCID: PMC5658156  PMID: 29073262
2.  Impact of Electronic Hand Hygiene Monitoring on Hospital-Acquired Clostridium difficile Infection Rates 
Open Forum Infectious Diseases  2017;4(Suppl 1):S407-S408.
Abstract
Background
Lower rates of hand hygiene adherence are linked to increased risk of nosocomial transmission of infectious pathogens, thereby increasing morbidity and mortality. Assessing true adherence is difficult using direct observation due to the low number of observations collected, heterogeneous observer training and bias, and the Hawthorne effect. We assessed whether radio frequency identification (RFID) hand hygiene monitoring resulted in changes to our hospital-onset Clostridium difficile (HO-CDI) rates. We also assessed whether electronically measured hand hygiene improved by the end of the intervention period.
Methods
The RFID system was installed in Apr 2016 in 2 medical/surgical units, a progressive care unit, and an intensive-care unit (study group). Registered nurses, certified nursing assistants, and selected physicians wore RFID badges to track hand hygiene adherence. Adherence is defined as washing with soap or alcohol-based hand rub within 1 minute before or after entering or exiting a patient’s room. A second set of rooms (1 ICU, 1 short-stay unit, and 5 medical/surgical units) without the system served as the control group. HO-CDI rates were tracked monthly for each group using NHSN definitions. HO-CDI trends were compared for 15 months before and 12 months after installation of the system using interrupted time series analysis. Average electronic hand hygiene adherence for the first two months and last two months of the intervention period was compared using the Wilcoxon rank-sum test. Other interventions aimed at reducing HO-CDI were consistently applied to both the study and control groups.
Results
One hundred and eighty-six HO-CDI occurred: 73 in the study group and 113 in the control group. In the study group, the trend in HO-CDI rates changed from increasing in the pre-intervention to decreasing in the post-intervention (P = 0.02) (Figure 1). HO-CDI rates in the control group demonstrated no change in trend (P = 0.69) (Figure 2). In the study group, electronically tracked hand hygiene adherence increased from a mean of 46% in Apr-May 2016, to 77% in Feb-Mar 2017 (P < 0.0001).
Conclusion
Electronic RFID hand hygiene systems can have a tangible effect on hospital-acquired infection rates. This result strengthens the argument for using these systems to improve patient safety.
Disclosures
All authors: No reported disclosures.
doi:10.1093/ofid/ofx163.1019
PMCID: PMC5631375
3.  Hospital Noninvasive Ventilation Case Volume and Outcomes of Acute Exacerbations of Chronic Obstructive Pulmonary Disease 
Rationale: Higher hospital case volume may produce local expertise (“practice makes perfect”), resulting in better patient outcomes. Associations between hospital noninvasive ventilation (NIV) case volume and outcomes for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) are unclear.
Objectives: To determine associations between total hospital NIV case volume for all indications and NIV failure and hospital mortality among patients with acute exacerbations of COPD.
Methods: Using the 2011 California State Inpatient Database and multivariable hierarchical logistic regression, we calculated hospital-level risk-adjusted rates for NIV failure (progression from NIV to invasive mechanical ventilation) and hospital mortality among patients with acute exacerbations of COPD.
Measurements and Main Results: We identified 37,516 hospitalizations for acute exacerbations of COPD in 252 California hospitals in 2011. Total hospital NIV use for all indications ranged from 2 to 565 cases (median, 64; interquartile range, 96). Hospital NIV failure rates for acute exacerbations of COPD ranged from 3.7 to 31.3% (median, 8.5%; interquartile range, 4.2). At the hospital level, higher total hospital NIV case volume was weakly associated with higher hospital NIV failure rates for acute exacerbations of COPD (r = 0.13; P = 0.03). Higher hospital NIV failure rates were weakly associated with higher hospital mortality rates for acute exacerbations of COPD (r = 0.15; P = 0.02), but higher total hospital NIV case volume was not associated with hospital mortality for exacerbations of COPD (r = −0.11; P = 0.08). At the patient level, patients admitted to high-NIV versus low-NIV case-volume hospitals had greater odds of NIV failure (quartile 4 vs. quartile 1 adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.12–3.40). Compared with initial treatment with invasive mechanical ventilation, NIV failure was associated with higher odds of death (aOR, 1.81; 95% CI, 1.35–2.44). However, admission to high-NIV versus low-NIV case-volume hospitals was not significantly associated with patient in-hospital mortality (quartile 4 vs. quartile 1 aOR, 0.76; 95% CI, 0.57–1.02).
Conclusions: Despite strong evidence for use of NIV in the management of acute exacerbations of COPD, we observed no significant mortality benefit and higher rates of NIV failure in high-NIV case-volume hospitals. Further investigation of patient selection and hospital factors associated with NIV failure is needed to maximize favorable patient outcomes associated with use of NIV for acute exacerbations of COPD.
doi:10.1513/AnnalsATS.201603-209OC
PMCID: PMC5122492  PMID: 27404021
chronic obstructive pulmonary disease; noninvasive ventilation; critical care outcomes; invasive mechanical ventilation; health care outcome assessment
4.  Proceedings of the 14th annual conference of INEBRIA 
Holloway, Aisha S. | Ferguson, Jennifer | Landale, Sarah | Cariola, Laura | Newbury-Birch, Dorothy | Flynn, Amy | Knight, John R. | Sherritt, Lon | Harris, Sion K. | O’Donnell, Amy J. | Kaner, Eileen | Hanratty, Barbara | Loree, Amy M. | Yonkers, Kimberly A. | Ondersma, Steven J. | Gilstead-Hayden, Kate | Martino, Steve | Adam, Angeline | Schwartz, Robert P. | Wu, Li-Tzy | Subramaniam, Geetha | Sharma, Gaurav | McNeely, Jennifer | Berman, Anne H. | Kolaas, Karoline | Petersén, Elisabeth | Bendtsen, Preben | Hedman, Erik | Linderoth, Catharina | Müssener, Ulrika | Sinadinovic, Kristina | Spak, Fredrik | Gremyr, Ida | Thurang, Anna | Mitchell, Ann M. | Finnell, Deborah | Savage, Christine L. | Mahmoud, Khadejah F. | Riordan, Benjamin C. | Conner, Tamlin S. | Flett, Jayde A. M. | Scarf, Damian | McRee, Bonnie | Vendetti, Janice | Gallucci, Karen Steinberg | Robaina, Kate | Clark, Brendan J. | Jones, Jacqueline | Reed, Kathryne D. | Hodapp, Rachel M. | Douglas, Ivor | Burnham, Ellen L. | Aagaard, Laura | Cook, Paul F. | Harris, Brett R. | Yu, Jiang | Wolff, Margaret | Rogers, Meighan | Barbosa, Carolina | Wedehase, Brendan J. | Dunlap, Laura J. | Mitchell, Shannon G. | Dusek, Kristi A. | Gryczynski, Jan | Kirk, Arethusa S. | Oros, Marla T. | Hosler, Colleen | O’Grady, Kevin E. | Brown, Barry S. | Angus, Colin | Sherborne, Sidney | Gillespie, Duncan | Meier, Petra | Brennan, Alan | de Vargas, Divane | Soares, Janaina | Castelblanco, Donna | Doran, Kelly M. | Wittman, Ian | Shelley, Donna | Rotrosen, John | Gelberg, Lillian | Edelman, E. Jennifer | Maisto, Stephen A. | Hansen, Nathan B. | Cutter, Christopher J. | Deng, Yanhong | Dziura, James | Fiellin, Lynn E. | O’Connor, Patrick G. | Bedimo, Roger | Gibert, Cynthia | Marconi, Vincent C. | Rimland, David | Rodriguez-Barradas, Maria C. | Simberkoff, Michael S. | Justice, Amy C. | Bryant, Kendall J. | Fiellin, David A. | Giles, Emma L. | Coulton, Simon | Deluca, Paolo | Drummond, Colin | Howel, Denise | McColl, Elaine | McGovern, Ruth | Scott, Stephanie | Stamp, Elaine | Sumnall, Harry | Vale, Luke | Alabani, Viviana | Atkinson, Amanda | Boniface, Sadie | Frankham, Jo | Gilvarry, Eilish | Hendrie, Nadine | Howe, Nicola | McGeechan, Grant J. | Ramsey, Amy | Stanley, Grant | Clephane, Justine | Gardiner, David | Holmes, John | Martin, Neil | Shevills, Colin | Soutar, Melanie | Chi, Felicia W. | Weisner, Constance | Ross, Thekla B. | Mertens, Jennifer | Sterling, Stacy A. | Shorter, Gillian W. | Heather, Nick | Bray, Jeremy | Cohen, Hildie A. | McPherson, Tracy L. | Adam, Cyrille | López-Pelayo, Hugo | Gual, Antoni | Segura-Garcia, Lidia | Colom, Joan | Ornelas, India J. | Doyle, Suzanne | Donovan, Dennis | Duran, Bonnie | Torres, Vanessa | Gaume, Jacques | Grazioli, Véronique | Fortini, Cristiana | Paroz, Sophie | Bertholet, Nicolas | Daeppen, Jean-Bernard | Satterfield, Jason M. | Gregorich, Steven | Alvarado, Nicholas J. | Muñoz, Ricardo | Kulieva, Gozel | Vijayaraghavan, Maya | Adam, Angéline | Cunningham, John A. | Díaz, Estela | Palacio-Vieira, Jorge | Godinho, Alexandra | Kushir, Vladyslav | O’Brien, Kimberly H. M. | Aguinaldo, Laika D. | Sellers, Christina M. | Spirito, Anthony | Chang, Grace | Blake-Lamb, Tiffany | LaFave, Lea R. Ayers | Thies, Kathleen M. | Pepin, Amy L. | Sprangers, Kara E. | Bradley, Martha | Jorgensen, Shasta | Catano, Nico A. | Murray, Adelaide R. | Schachter, Deborah | Andersen, Ronald M. | Rey, Guillermina Natera | Vahidi, Mani | Rico, Melvin W. | Baumeister, Sebastian E. | Johansson, Magnus | Sinadinovic, Christina | Hermansson, Ulric | Andreasson, Sven | O’Grady, Megan A. | Kapoor, Sandeep | Akkari, Cherine | Bernal, Camila | Pappacena, Kristen | Morley, Jeanne | Auerbach, Mark | Neighbors, Charles J. | Kwon, Nancy | Conigliaro, Joseph | Morgenstern, Jon | Magill, Molly | Apodaca, Timothy R. | Borsari, Brian | Hoadley, Ariel | Scott Tonigan, J. | Moyers, Theresa | Fitzgerald, Niamh M. | Schölin, Lisa | Barticevic, Nicolas | Zuzulich, Soledad | Poblete, Fernando | Norambuena, Pablo | Sacco, Paul | Ting, Laura | Beaulieu, Michele | Wallace, Paul George | Andrews, Matthew | Daley, Kate | Shenker, Don | Gallagher, Louise | Watson, Rod | Weaver, Tim | Bruguera, Pol | Oliveras, Clara | Gavotti, Carolina | Barrio, Pablo | Braddick, Fleur | Miquel, Laia | Suárez, Montse | Bruguera, Carla | Brown, Richard L. | Capell, Julie Whelan | Paul Moberg, D. | Maslowsky, Julie | Saunders, Laura A. | McCormack, Ryan P. | Scheidell, Joy | Gonzalez, Mirelis | Bauroth, Sabrina | Liu, Weiwei | Lindsay, Dawn L. | Lincoln, Piper | Hagle, Holly | Wallhed Finn, Sara | Hammarberg, Anders | Andréasson, Sven | King, Sarah E. | Vargo, Rachael | Kameg, Brayden N. | Acquavita, Shauna P. | Van Loon, Ruth Anne | Smith, Rachel | Brehm, Bonnie J. | Diers, Tiffiny | Kim, Karissa | Barker, Andrea | Jones, Ashley L. | Skinner, Asheley C. | Hinman, Agatha | Svikis, Dace S. | Thacker, Casey L. | Resnicow, Ken | Beatty, Jessica R. | Janisse, James | Puder, Karoline | Bakshi, Ann-Sofie | Milward, Joanna M. | Kimergard, Andreas | Garnett, Claire V. | Crane, David | Brown, Jamie | West, Robert | Michie, Susan | Rosendahl, Ingvar | Andersson, Claes | Gajecki, Mikael | Blankers, Matthijs | Donoghue, Kim | Lynch, Ellen | Maconochie, Ian | Phillips, Ceri | Pockett, Rhys | Phillips, Tom | Patton, R. | Russell, Ian | Strang, John | Stewart, Maureen T. | Quinn, Amity E. | Brolin, Mary | Evans, Brooke | Horgan, Constance M. | Liu, Junqing | McCree, Fern | Kanovsky, Doug | Oberlander, Tyler | Zhang, Huan | Hamlin, Ben | Saunders, Robert | Barton, Mary B. | Scholle, Sarah H. | Santora, Patricia | Bhatt, Chirag | Ahmed, Kazi | Hodgkin, Dominic | Gao, Wenwu | Merrick, Elizabeth L. | Drebing, Charles E. | Larson, Mary Jo | Sharma, Monica | Petry, Nancy M. | Saitz, Richard | Weisner, Constance M. | Young-Wolff, Kelly C. | Lu, Wendy Y. | Blosnich, John R. | Lehavot, Keren | Glass, Joseph E. | Williams, Emily C. | Bensley, Kara M. | Chan, Gary | Dombrowski, Julie | Fortney, John | Rubinsky, Anna D. | Lapham, Gwen T. | Forray, Ariadna | Olmstead, Todd A. | Gilstad-Hayden, Kathryn | Kershaw, Trace | Dillon, Pamela | Weaver, Michael F. | Grekin, Emily R. | Ellis, Jennifer D. | McGoron, Lucy | McGoron, Lucy
doi:10.1186/s13722-017-0087-8
PMCID: PMC5606215
5.  Urinary Glycosaminoglycans Predict Outcomes in Septic Shock and Acute Respiratory Distress Syndrome 
Rationale: Degradation of the endothelial glycocalyx, a glycosaminoglycan (GAG)-rich layer lining the vascular lumen, is associated with the onset of kidney injury in animal models of critical illness. It is unclear if similar pathogenic degradation occurs in critically ill patients.
Objectives: To determine if urinary indices of GAG fragmentation are associated with outcomes in patients with critical illnesses such as septic shock or acute respiratory distress syndrome (ARDS).
Methods: We prospectively collected urine from 30 patients within 24 hours of admission to the Denver Health Medical Intensive Care Unit (ICU) for septic shock. As a nonseptic ICU control, we collected urine from 25 surgical ICU patients admitted for trauma. As a medical ICU validation cohort, we obtained serially collected urine samples from 70 patients with ARDS. We performed mass spectrometry on urine samples to determine GAG (heparan sulfate, chondroitin sulfate, and hyaluronic acid) concentrations as well as patterns of heparan sulfate/chondroitin sulfate disaccharide sulfation. We compared these indices to measurements obtained using dimethylmethylene blue, an inexpensive, colorimetric urinary assay of sulfated GAGs.
Measurements and Main Results: In septic shock, indices of GAG fragmentation correlated with both the development of renal dysfunction over the 72 hours after urine collection and with hospital mortality. This association remained after controlling for severity of illness and was similarly observed using the inexpensive dimethylmethylene blue assay. These predictive findings were corroborated using urine samples previously collected at three consecutive time points from patients with ARDS.
Conclusions: Early indices of urinary GAG fragmentation predict acute kidney injury and in-hospital mortality in patients with septic shock or ARDS.
Clinical trial registered with www.clinicaltrials.gov (NCT01900275).
doi:10.1164/rccm.201511-2281OC
PMCID: PMC5003330  PMID: 26926297
glycocalyx; heparan sulfate; chondroitin sulfate; hyaluronic acid; glycomics
6.  The history of risk: a review 
In the USA alone, around 22 million patients annually discuss the need for surgical procedure with their surgeon. On a global scale, more than 200 million patients are exposed to the risk of undergoing a surgical procedure every year. A crucial part of the informed consent process for surgery is the understanding of risk, the probability of complications, and the predicted occurrence of adverse events. Ironically, risk quantification, risk stratification, and risk management are not necessarily part of a surgeon’s core skillset, considering the lengthy surgical training curriculum towards technical excellence. The present review was designed to provide a concise historic perspective on the evolution of our current understanding of risk and probability, which represent the key underlying pillars of the shared decision-making process between surgeons and patients when discussing surgical treatment options.
doi:10.1186/s13017-017-0125-6
PMCID: PMC5348843
Risk; History; Probability theory; Risk management; Decision-making
7.  Comparison of Bag-Valve-Mask Hand-Sealing Techniques in a Simulated Model 
Annals of emergency medicine  2013;63(1):6-12.e3.
Study objective
Bag-valve-mask ventilation remains an essential component of airway management. Rescuers continue to use both traditional 1- or 2-handed mask-face sealing techniques, as well as a newer modified 2-handed technique. We compare the efficacy of 1-handed, 2-handed, and modified 2-handed bag-valve-mask technique.
Methods
In this prospective, crossover study, health care providers performed 1-handed, 2-handed, and modified 2-handed bag-valve-mask ventilation on a standardized ventilation model. Subjects performed each technique for 5 minutes, with 3 minutes’ rest between techniques. The primary outcome was expired tidal volume, defined as percentage of total possible expired tidal volume during a 5-minute bout. A specialized inline monitor measured expired tidal volume. We compared 2-handed versus modified 2-handed and 2-handed versus 1-handed techniques.
Results
We enrolled 52 subjects: 28 (54%) men, 32 (62%) with greater than or equal to 5 actual emergency bag-valve-mask situations. Median expired tidal volume percentage for 1-handed technique was 31% (95% confidence interval [CI] 17% to 51%); for 2-handed technique, 85% (95% CI 78% to 91%); and for modified 2-handed technique, 85% (95% CI 82% to 90%). Both 2-handed (median difference 47%; 95% CI 34% to 62%) and modified 2-handed technique (median difference 56%; 95% CI 29% to 65%) resulted in significantly higher median expired tidal volume percentages compared with 1-handed technique. The median expired tidal volume percentages between 2-handed and modified 2-handed techniques did not significantly differ from each other (median difference 0; 95% CI −2% to 2%).
Conclusion
In a simulated model, both 2-handed mask-face sealing techniques resulted in higher ventilatory tidal volumes than 1-handed technique. Tidal volumes from 2-handed and modified 2-handed techniques did not differ. Rescuers should perform bag-valve-mask ventilation with 2-handed techniques.
doi:10.1016/j.annemergmed.2013.07.014
PMCID: PMC4866830  PMID: 23937957
8.  Analysis of Total Human Urinary Glycosaminoglycan Disaccharides by Liquid Chromatography–Tandem Mass Spectrometry 
Analytical chemistry  2015;87(12):6220-6227.
The determination of complex analytes, present at low concentrations, in biological fluids poses a diffcult challenge. This study relies on an optimized method of recovery, enzymatic treatment, and disaccharide analysis by liquid chromatography–tandem mass spectrometry to rapidly determine low concentrations of glycosaminoglycans in human urine. The approach utilizes multiple reaction monitoring (MRM) of glycosaminoglycan disaccharides obtained from treating urine samples with recombinant heparin lyases and chondroitin lyase. This rapid and sensitive method allows the analysis of glycosaminoglycan content and disaccharide composition in urine samples having concentrations 10-to 100-fold lower than those typically analyzed from patients with metabolic diseases, such as mucopolysaccharidosis. The current method facilitates the analysis low (ng/mL) levels of urinary glycosaminoglycans present in healthy individuals and in patients with pathological conditions, such as inflammation and cancers, that can subtly alter glycosaminoglycan content and composition.
doi:10.1021/acs.analchem.5b00913
PMCID: PMC4822829  PMID: 26005898
9.  Development and Validation of a Mortality Prediction Model for Patients Receiving 14 Days of Mechanical Ventilation 
Critical care medicine  2015;43(11):2339-2345.
Objectives
The existing risk prediction model for patients requiring prolonged mechanical ventilation is not applicable until after 21 days of mechanical ventilation. We sought to develop and validate a mortality prediction model for patients earlier in the ICU course using data from day 14 of mechanical ventilation.
Study Design
Multi-center retrospective cohort study.
Patients
Adult patients receiving at least 14 days of mechanical ventilation at 5 medical centers (development cohort) or enrolled in the ARDS Network FACTT trial (validation cohort).
Measurements and Main Results
Predictor variables were measured on day 14 of mechanical ventilation in the development cohort and included in a logistic regression model with one-year mortality as the outcome. Variables were sequentially eliminated to develop the ProVent 14 model. This model was then generated in the validation cohort. A simplified prognostic scoring rule (ProVent 14 Score) using categorical variables was created in the development cohort and then tested in the validation cohort. Model discrimination was assessed by the area under the receiver-operator characteristic curve (AUC).
491 patients and 245 patients were included in the development and validation cohorts, respectively. The most parsimonious model included age, platelet count, requirement for vasopressors, requirement for hemodialysis, and non-trauma admission. The AUC for the ProVent 14 model using continuous variables was 0.80 (95% CI, 0.76–0.83) in the development cohort and 0.78 (95% CI, 0.72–0.83) in the validation cohort. The ProVent 14 Score categorized age at 50 and 65 years old, and categorized platelet count at 100 × 109/L, and had similar discrimination as the ProVent 14 model in both cohorts.
Conclusion
Using clinical variables available on day 14 of mechanical ventilation, the ProVent14 model can identify patients receiving prolonged mechanical ventilation with a high risk of mortality within one year.
doi:10.1097/CCM.0000000000001205
PMCID: PMC4788381  PMID: 26247337
Prolonged mechanical ventilation; outcomes; prognosis; critical care; communication; multiple organ failure; decision making
10.  Rapid Automated Microscopy for Microbiological Surveillance of Ventilator-associated Pneumonia 
Rationale: Diagnosis of ventilator-associated pneumonia (VAP) is imprecise.
Objectives: To (1) determine whether alternate-day surveillance mini–bronchoalveolar lavage (mini-BAL) in ventilated adults could reduce time to initiation of targeted treatment and (2) evaluate the potential for automated microscopy to reduce analysis time.
Methods: Adult intensive care unit patients who were anticipated to require ventilation for at least a further 48 hours were included. Mini-BALs were processed for identification, quantitation, and antibiotic susceptibility, using (1) clinical culture (50 ± 7 h) and (2) automated microscopy (∼5 h plus offline analysis).
Measurements and Main Results: Seventy-seven mini-BALs were performed in 33 patients. One patient (3%) was clinically diagnosed with VAP. Of 73 paired samples, culture identified 7 containing pneumonia panel bacteria (>104 colony-forming units/ml) from five patients (15%) (4 Staphylococcus aureus [3 methicillin-resistant S. aureus], 2 Stenotrophomonas maltophilia, 1 Klebsiella pneumoniae) and resulted in antimicrobial changes/additions to two of five (40%) of those patients. Microscopy identified 7 of 7 microbiologically positive organisms and 64 of 66 negative samples compared with culture. Antimicrobial responses were concordant in four of five comparisons. Antimicrobial changes/additions would have occurred in three of seven microscopy-positive patients (43%) had those results been clinically available in 5 hours, including one patient diagnosed later with VAP despite negative mini-BAL cultures.
Conclusions: Microbiological surveillance detected infection in patients at risk for VAP independent of clinical signs, resulting in changes to antimicrobial therapy. Automated microscopy was 100% sensitive and 97% specific for high-risk pneumonia organisms compared with clinical culturing. Rapid microscopy-based surveillance may be informative for treatment and antimicrobial stewardship in patients at risk for VAP.
doi:10.1164/rccm.201408-1468OC
PMCID: PMC4384769  PMID: 25585163
nosocomial infections; ventilator-associated pneumonia; microbiological techniques
12.  Sensitivity of Systemic Inflammatory Response Syndrome for Critical Illness Among Emergency Department Patients 
Background
Little is known about the diagnostic accuracy of Systemic inflammatory response syndrome (SIRS) criteria for critical illness among emergency department (ED) patients with and without infection. Our objective was to assess the diagnostic accuracy of systemic inflammatory response syndrome (SIRS) criteria for critical illness in ED patients.
Methods
This was a retrospective cohort study of ED patients at an urban academic hospital. Standardized chart abstraction was performed on a random sample of all adult ED medical patients admitted to the hospital during a 1-year period, excluding repeat visits, transfers, ED deaths, and primary surgical or psychiatric admissions. The binary composite outcome of critical illness was defined as ≥24 hours in intensive care or in-hospital death. Presumed infection was defined as receiving antibiotics within 48 hours of admission. SIRS criteria were calculated using ED triage vital signs and initial white blood cell count.
Results
We studied 1,152 patients; 39% had SIRS, 27% had presumed infection, and 23% had critical illness (2% had in-hospital mortality, 22% had ≥24 hours in intensive care). Of patients with SIRS, 38% had presumed infection. Of patients without SIRS, 21% had presumed infection. The sensitivity of SIRS criteria for critical illness was 52% (95% confidence interval [CI] 46%–58%) in all patients, 66% (95% CI 56%–75%) in patients with presumed infection, and 43% (95% CI 36%–51%) in patients without presumed infection.
Conclusions
SIRS at ED triage, as currently defined, has poor sensitivity for critical illness in medical patients admitted from the ED.
doi:10.1016/j.ajem.2014.07.035
PMCID: PMC4254326  PMID: 25205616
systemic inflammatory response syndrome; critical illness; sensitivity and specificity; diagnosis; emergency medicine; sepsis
13.  Early Effect of Tidal Volume on Lung Injury Biomarkers in Surgical Patients with Healthy Lungs 
Anesthesiology  2014;121(3):469-481.
Background
The early biological impact of short-term mechanical ventilation on healthy lungs is unknown. We aimed to characterize the immediate tidal volume (VT)-related changes on lung injury biomarkers in patients with healthy lungs and low risk of pulmonary complications.
Methods
Twenty-eight healthy patients for knee replacement surgery were prospectively randomized to volume-controlled ventilation with VT 6 (VT6) or 10 (VT10) mL/kg predicted body weight. General anesthesia and other ventilatory parameters (positive end-expiratory pressure 5 cmH2O, FiO2 0.5, respiratory rate titrated for normocapnia) were managed similarly in the two groups. Exhaled breath condensate (EBC) and blood samples were collected for nitrite, nitrate, tumor necrosis factor α, interleukins-1β, 6, 8, 10, 11, neutrophil elastase (NE), and Clara Cell protein 16 (CC16) measurements, at the onset of ventilation and 60 min later.
Results
No significant differences in biomarkers were detected between the VT groups at any time. The coefficient of variation of EBC nitrite and nitrate decreased in the VT6 but increased in the VT10 group after 60-min ventilation. Sixty minute ventilation significantly increased plasma NE levels in the VT6 (35.2 ± 30.4 vs. 56.4 ± 51.7 ng/mL, P = 0.008) and CC16 levels in the VT10 group (16.4 ± 8.8 vs. 18.7 ± 9.5 ng/mL, P = 0.015). EBC nitrite correlated with plateau pressure (r = 0.27, P = 0.042) and plasma NE (r = 0.44, P = 0.001). Plasma CC16 correlated with compliance (r = 0.34, P = 0.014).
Conclusion
No tidal volume-related changes were observed in the selected lung injury biomarkers of patients with healthy lungs after 60-min ventilation. Plasma NE and plasma CC16 might indicate atelectrauma and lung distention, respectively.
doi:10.1097/ALN.0000000000000301
PMCID: PMC4165799  PMID: 24809976
14.  Medicaid Expansion under the Affordable Care Act. Implications for Insurance-related Disparities in Pulmonary, Critical Care, and Sleep 
The Affordable Care Act was intended to address systematic health inequalities for millions of Americans who lacked health insurance. Expansion of Medicaid was a key component of the legislation, as it was expected to provide coverage to low-income individuals, a population at greater risk for disparities in access to the health care system and in health outcomes. Several studies suggest that expansion of Medicaid can reduce insurance-related disparities, creating optimism surrounding the potential impact of the Affordable Care Act on the health of the poor. However, several impediments to the implementation of Medicaid’s expansion and inadequacies within the Medicaid program itself will lessen its initial impact. In particular, the Supreme Court’s decision to void the Affordable Care Act’s mandate requiring all states to accept the Medicaid expansion allowed half of the states to forego coverage expansion, leaving millions of low-income individuals without insurance. Moreover, relative to many private plans, Medicaid is an imperfect program suffering from lower reimbursement rates, fewer covered services, and incomplete acceptance by preventive and specialty care providers. These constraints will reduce the potential impact of the expansion for patients with respiratory and sleep conditions or critical illness. Despite its imperfections, the more than 10 million low-income individuals who gain insurance as a result of Medicaid expansion will likely have increased access to health care, reduced out-of-pocket health care spending, and ultimately improvements in their overall health.
doi:10.1513/AnnalsATS.201402-072PS
PMCID: PMC4225799  PMID: 24708065
Patient Protection and Affordable Care Act; Medicaid; health policy; insurance, health
15.  An Official American Thoracic Society Workshop Report: Developing Performance Measures from Clinical Practice Guidelines 
Many health care performance measures are either not based on high-quality clinical evidence or not tightly linked to patient-centered outcomes, limiting their usefulness in quality improvement. In this report we summarize the proceedings of an American Thoracic Society workshop convened to address this problem by reviewing current approaches to performance measure development and creating a framework for developing high-quality performance measures by basing them directly on recommendations from well-constructed clinical practice guidelines. Workshop participants concluded that ideally performance measures addressing care processes should be linked to clinical practice guidelines that explicitly rate the quality of evidence and the strength of recommendations, such as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. Under this framework, process-based performance measures would only be developed from strong recommendations based on high- or moderate-quality evidence. This approach would help ensure that clinical processes specified in performance measures are both of clear benefit to patients and supported by strong evidence. Although this approach may result in fewer performance measures, it would substantially increase the likelihood that quality-improvement programs based on these measures actually improve patient care.
doi:10.1513/AnnalsATS.201403-106ST
PMCID: PMC5469393  PMID: 24828810
16.  Angiogenesis in Chronic Lung Disease 
Chest  2007;131(3):874-879.
Chronic lung diseases like COPD, severe progressive pulmonary hypertension (PH), and interstitial lung diseases all have a lung vascular disease component. Cellular and molecular mechanisms of pulmonary vascular remodeling have been experimentally explored in many animal models, and it is now clear that microvessels are involved. In emphysema patients, there is a loss of lung microvessels, and in many forms of severe PH there is obliteration of precapillary arterioles by angioproliferation. Thus, COPD/emphysema and severe angioproliferative PH are on the opposite ends of a spectrum of vascular biology responses. Animal experiments have provided insight regarding some of the initiating events that shape the various forms of pulmonary vascular remodeling. In pulmonary fibrosis and in the postinjury phase of acute lung injury, the angiogenic/angiostatic balance is also affected. This review will therefore discuss angiogenesis in several chronic lung diseases and will speculate on how altered vascular homeostasis may contribute to lung disease development.
doi:10.1378/chest.06-2453
PMCID: PMC4396181  PMID: 17356107
acute lung injury; angiogenesis; COPD; interstitial lung disease; lung structure maintenance program; pulmonary hypertension
17.  The Circulating Glycosaminoglycan Signature of Respiratory Failure in Critically Ill Adults* 
The Journal of Biological Chemistry  2014;289(12):8194-8202.
Background: Endothelial glycocalyx degradation contributes to the pathogenesis of critical illness.
Results: Mechanically ventilated subjects exhibited plasma glycocalyx breakdown signatures (glycosaminoglycan fragments) characteristic of direct versus indirect etiologies of respiratory failure.
Conclusion: Circulating glycosaminoglycans provide insight into respiratory failure pathophysiology.
Significance: This is the first study to characterize circulating glycosaminoglycans during critical illness, offering insight into the mechanisms underlying respiratory failure.
Systemic inflammatory illnesses (such as sepsis) are marked by degradation of the endothelial glycocalyx, a layer of glycosaminoglycans (including heparan sulfate, chondroitin sulfate, and hyaluronic acid) lining the vascular lumen. We hypothesized that different pathophysiologic insults would produce characteristic patterns of released glycocalyx fragments. We collected plasma from healthy donors as well as from subjects with respiratory failure due to altered mental status (intoxication, ischemic brain injury), indirect lung injury (non-pulmonary sepsis, pancreatitis), or direct lung injury (aspiration, pneumonia). Mass spectrometry was employed to determine the quantity and sulfation patterns of circulating glycosaminoglycans. We found that circulating heparan sulfate fragments were significantly (23-fold) elevated in patients with indirect lung injury, while circulating hyaluronic acid concentrations were elevated (32-fold) in patients with direct lung injury. N-Sulfation and tri-sulfation of heparan disaccharides were significantly increased in patients with indirect lung injury. Chondroitin disaccharide sulfation was suppressed in all groups with respiratory failure. Plasma heparan sulfate concentrations directly correlated with intensive care unit length of stay. Serial plasma measurements performed in select patients revealed that circulating highly sulfated heparan fragments persisted for greater than 3 days after the onset of respiratory failure. Our findings demonstrate that circulating glycosaminoglycans are elevated in patterns characteristic of the etiology of respiratory failure and may serve as diagnostic and/or prognostic biomarkers of critical illness.
doi:10.1074/jbc.M113.539452
PMCID: PMC3961648  PMID: 24509853
Chondroitin Sulfate; Glycobiology; Heparan Sulfate; Hyaluronate; Lung Injury; Sepsis; Endothelial Glycocalyx; Respiratory Failure
18.  Healthcare Utilization in Medical Intensive Care Unit Survivors with Alcohol Withdrawal 
Background
Rehospitalization is an important and costly outcome that occurs commonly in several diseases encountered in the medical intensive care unit (ICU). Although alcohol use disorders are present in 40% of ICU survivors and alcohol withdrawal is the most common alcohol-related reason for admission to an ICU, rates and predictors of rehospitalization have not been previously reported in this population.
Methods
We conducted a retrospective cohort study of medical ICU survivors with a primary or secondary discharge diagnosis of alcohol withdrawal using two administrative databases. The primary outcome was time to rehospitalization or death. Secondary outcomes included time to first emergency department or urgent care clinic visit in the subset of ICU survivors who were not rehospitalized. Cox proportional hazard models were adjusted for age, gender, race, homelessness, smoking, and payer source.
Results
Of 1,178 patients discharged from the medical ICU over the study period, 468 (40%) were readmitted to the hospital and 54 (4%) died within 1 year. Schizophrenia (HR 2.23, 95% CI 1.57, 3.34, p < 0.001), anxiety disorder (HR 2.04, 95% CI 1.30, 3.32, p < 0.01), depression (HR 1.62, 95% CI 1.05, 2.40, p = 0.03), and Deyo comorbidity score ≥ 3 (HR 1.43, 95% CI 1.09, 1.1.89, p = 0.01) were significant predictors of time to death or first rehospitalization. Bipolar disorder was associated with time to first emergency department or urgent care clinic visit (HR 2.03, 95% CI 1.24, 3.62, p < 0.01) in the 656 patients who were alive and not rehospitalized within one year.
Conclusion
The presence of a psychiatric comorbidity is a significant predictor of multiple measures of unplanned healthcare utilization in medical ICU survivors with a primary or secondary discharge diagnosis of alcohol withdrawal. This finding highlights the potential importance of targeting longitudinal multidisciplinary care to patients with a dual diagnosis.
doi:10.1111/acer.12124
PMCID: PMC4045620  PMID: 23647435
alcohol withdrawal; alcohol use disorder; intensive care unit; rehospitalization; dual diagnosis
19.  5-Lipoxygenase Activating Protein (FLAP) Dependent Leukotriene Biosynthesis Inhibition (MK591) Attenuates Lipid A Endotoxin-Induced Inflammation 
PLoS ONE  2014;9(7):e102622.
The Lipid A moiety of endotoxin potently activates TLR-4 dependent host innate immune responses. We demonstrate that Lipid-A mediated leukotriene biosynthesis regulates pathogen-associated molecular patterns (PAMP)-dependent macrophage activation. Stimulation of murine macrophages (RAW264.7) with E. coli 0111:B4 endotoxin (LPS) or Kdo2-lipid A (Lipid A) induced inflammation and Lipid A was sufficient to induce TLR-4 mediated macrophage inflammation and rapid ERK activation. The contribution of leukotriene biosynthesis was evaluated with a 5-lipoxygenase activating protein (FLAP) inhibitor, MK591. MK591 pre-treatment not only enhanced but also sustained ERK activation for up to 4 hours after LPS and Lipid A stimulation while inhibiting cell proliferation and enhancing cellular apoptosis. Leukotriene biosynthesis inhibition attenuated inflammation induced by either whole LPS or the Lipid A fraction. These responses were regulated by inhibition of the key biosynthesis enzymes for the proinflammatory eicosanoids, 5-lipoxygenase (5-LO), and cyclooxygenase-2 (COX-2) quantified by immunoblotting. Inhibition of leukotriene biosynthesis differentially regulated TLR-2 and TLR-4 cell surface expression assessed by flow cytometry, suggesting a close mechanistic association between TLR expression and 5-LO associated eicosanoid activity in activated macrophages. Furthermore, MK591 pre-treatment enhanced ERK activation and inhibited cell proliferation after LPS or Lipid A stimulation. These effects were regulated in part by increased apoptosis and modulation of cell surface TLR expression. Together, these data clarify the mechanistic association between 5-lipoxygenase activating protein-mediated leukotriene biosynthesis and 5-LO dependent eicosanoid metabolites in mediating the TLR-dependent inflammatory response after endotoxin exposure typical of bacterial sepsis.
doi:10.1371/journal.pone.0102622
PMCID: PMC4099325  PMID: 25025775
20.  The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis 
Nature medicine  2012;18(8):10.1038/nm.2843.
Sepsis, a systemic inflammatory response to infection, commonly progresses to acute lung injury (ALI), an inflammatory lung disease with high morbidity. We postulated that sepsis-associated ALI is initiated by degradation of the pulmonary endothelial glycocalyx, leading to neutrophil adherence and inflammation. Using intravital microscopy, we found that endotoxemia in mice rapidly induced pulmonary microvascular glycocalyx degradation via tumor necrosis factor-α (TNF-α)-dependent mechanisms. Glycocalyx degradation involved the specific loss of heparan sulfate and coincided with activation of endothelial heparanase, a TNF-α–responsive, heparan sulfate–specific glucuronidase. Glycocalyx degradation increased the availability of endothelial surface adhesion molecules to circulating microspheres and contributed to neutrophil adhesion. Heparanase inhibition prevented endotoxemia-associated glycocalyx loss and neutrophil adhesion and, accordingly, attenuated sepsis-induced ALI and mortality in mice. These findings are potentially relevant to human disease, as sepsis-associated respiratory failure in humans was associated with higher plasma heparan sulfate degradation activity; moreover, heparanase content was higher in human lung biopsies showing diffuse alveolar damage than in normal human lung tissue.
doi:10.1038/nm.2843
PMCID: PMC3723751  PMID: 22820644
21.  Mitogen-activated Protein Kinase Phosphatase-1 Modulates Regional Effects of Injurious Mechanical Ventilation in Rodent Lungs 
Rationale: Mechanical ventilation induces heterogeneous lung injury by mitogen-activated protein kinase (MAPK) and nuclear factor-κB. Mechanisms regulating regional injury and protective effects of prone positioning are unclear.
Objectives: To determine the key regulators of the lung regional protective effects of prone positioning in rodent lungs exposed to injurious ventilation.
Methods: Adult rats were ventilated with high (18 ml/kg, positive end-expiratory pressure [PEEP] 0) or low Vt (6 ml/kg; PEEP 3 cm H2O; 3 h) in supine or prone position. Dorsal–caudal lung mRNA was analyzed by microarray and MAPK phosphatases (MKP)-1 quantitative polymerase chain reaction. MKP-1−/− or wild-type mice were ventilated with very high (24 ml/kg; PEEP 0) or low Vt (6–7 ml/kg; PEEP 3 cm H2O). The MKP-1 regulator PG490-88 (MRx-108; 0.75 mg/kg) or phosphate-buffered saline was administered preventilation. Injury was assessed by lung mechanics, bronchioalveolar lavage cell counts, protein content, and lung injury scoring. Immunoblotting for MKP-1, and IκBα and cytokine ELISAs were performed on lung lysates.
Measurements and Main Results: Prone positioning was protective against injurious ventilation in rats. Expression profiling demonstrated MKP-1 20-fold higher in rats ventilated prone rather than supine and regional reduction in p38 and c-jun N-terminal kinase activation. MKP-1−/− mice experienced amplified injury. PG490-88 improved static lung compliance and injury scores, reduced bronchioalveolar lavage cell counts and cytokine levels, and induced MKP-1 and IκBα.
Conclusions: Injurious ventilation induces MAPK in an MKP-1–dependent fashion. Prone positioning is protective and induces MKP-1. PG490-88 induced MKP-1 and was protective against high Vt in a nuclear factor-κB–dependent manner. MKP-1 is a potential target for modulating regional effects of injurious ventilation.
doi:10.1164/rccm.201109-1593OC
PMCID: PMC3400991  PMID: 22582160
regionally injurious ventilation; prone position; rodent lung injury; MKP-1/DUSP-1; triptolide
22.  Severity of Acute Illness is Associated with Baseline Readiness to Change in Medical Intensive Care Unit Patients with Unhealthy Alcohol Use 
Introduction
Unhealthy alcohol use predisposes to multiple conditions that frequently result in critical illness and is present in up to one-third of patients admitted to a medical intensive care unit (ICU). We sought to determine the baseline readiness to change in medical ICU patients with unhealthy alcohol use and hypothesized that the severity of acute illness would be independently associated with higher scores on readiness to change scales. We further sought to determine whether this effect is modified by the severity of unhealthy alcohol use.
Materials and Methods
We performed a cross-sectional observational study of current regular drinkers in three medical ICUs. The Alcohol Use Disorders Identification Test was used to differentiate low risk and unhealthy alcohol use and further categorize patients into risky alcohol use or an alcohol use disorder. The severity of a patient’s acute illness was assessed by calculating the Acute Physiology and Chronic Healthy Evaluation II score at the time of admission to the medical ICU. Readiness to change was assessed using standardized questionnaires.
Results
Of 101 medical ICU patients who were enrolled, 65 met the criteria for unhealthy alcohol use. The association between the severity of acute illness and readiness to change depended on the instrument used. A higher severity of illness measured by APACHEII score was an independent predictor of readiness to change as assessed by the Stages of Change Readiness and Treatment Eagerness Scale (Taking Action scale) (p< 0.01). When a visual analog scale was used to assess readiness to change, there was a significant association with severity of acute illness (p < 0.01) that was modified by the severity of unhealthy alcohol use (p = 0.04 for interaction term).
Conclusion
Medical ICU patients represent a population where brief interventions require further study. Studies of brief intervention should account for the severity of acute illness and the severity of unhealthy alcohol use as potential effect modifiers.
doi:10.1111/j.1530-0277.2011.01648.x
PMCID: PMC3251713  PMID: 21950704
23.  Acute Kidney Injury in Patients with Acute Lung Injury: Impact of Fluid Accumulation on Classification of Acute Kidney Injury and Associated Outcomes 
Critical care medicine  2011;39(12):2665-2671.
Objective
It has been suggested that fluid accumulation may delay recognition of acute kidney injury (AKI). We sought to determine the impact of fluid balance on the incidence of non-dialysis requiring AKI in patients with acute lung injury and to describe associated outcomes, including mortality.
Design
Analysis of the Fluid and Catheter Treatment Trial, a factorial randomized clinical trial of conservative versus liberal fluid management and of management guided by a central venous versus pulmonary artery catheter.
Setting and Patients
1000 patients at ARDS Network hospitals.
Measurements and Main Results
The incidence of AKI, defined as an absolute rise in creatinine of ≥ 0.3 mg/dL or a relative change of > 50% over 48 hours, was examined before and after adjustment of serum creatinine for fluid balance. The incidence of AKI before adjustment for fluid balance was greater in those managed with the conservative fluid protocol (57 versus 51%, p = 0.04). After adjustment for fluid balance, the incidence of AKI was greater in those managed with the liberal fluid protocol (66 versus 58%, p = 0.007). Patients who met AKI criteria after adjustment of creatinine for fluid balance (but not before) had a mortality rate that was significantly greater than those who did not meet AKI criteria both before and after adjustment for fluid balance (31 versus 12%, p < 0.001) and those who had AKI before but not after adjustment for fluid balance (31 versus 11%, p = 0.005). The mortality of those patients meeting AKI criteria after but not before adjustment for fluid balance was similar to patients with AKI both before and after adjustment for fluid balance (31% versus 38%, p = 0.18).
Conclusions
Fluid management influences serum creatinine and therefore the diagnosis of AKI using creatinine-based definitions. Patients with “unrecognized” AKI that is identified after adjusting for positive fluid balance have high mortality rates, and patients who have AKI before but not after adjusting for fluid balance have low mortality rates. Future studies of AKI should consider potential differences in serum creatinine caused by changes in fluid balance and the impact of these differences on diagnosis and prognosis.
doi:10.1097/CCM.0b013e318228234b
PMCID: PMC3220741  PMID: 21785346
Acute kidney injury; acute lung injury; acute respiratory distress syndrome; fluid balance; creatinine; mortality
24.  A multicenter mortality prediction model for patients receiving prolonged mechanical ventilation 
Critical Care Medicine  2012;40(4):1171-1176.
Objective
Significant deficiencies exist in the communication of prognosis for patients requiring prolonged mechanical ventilation after acute illness, in part because of clinician uncertainty about long-term outcomes. We sought to refine a mortality prediction model for patients requiring prolonged ventilation using a multicentered study design.
Design
Cohort study.
Setting
Five geographically diverse tertiary care medical centers in the United States (California, Colorado, North Carolina, Pennsylvania, Washington).
Patients
Two hundred sixty adult patients who received at least 21 days of mechanical ventilation after acute illness.
Interventions
None.
Measurements and Main Results
For the probability model, we included age, platelet count, and requirement for vasopressors and/or hemodialysis, each measured on day 21 of mechanical ventilation, in a logistic regression model with 1-yr mortality as the outcome variable. We subsequently modified a simplified prognostic scoring rule (ProVent score) by categorizing the risk variables (age 18–49, 50–64, and >65 yrs; platelet count 0–150 and >150; vasopressors; hemodialysis) in another logistic regression model and assigning points to variables according to β coefficient values. Overall mortality at 1 yr was 48%. The area under the curve of the receiver operator characteristic curve for the primary ProVent probability model was 0.79 (95% confidence interval, 0.75–0.81), and the p value for the Hosmer-Lemeshow goodness-of-fit statistic was .89. The area under the curve for the categorical model was 0.77, and the p value for the goodness-of-fit statistic was .34. The area under the curve for the ProVent score was 0.76, and the p value for the Hosmer-Lemeshow goodness-of-fit statistic was .60. For the 50 patients with a ProVent score >2, only one patient was able to be discharged directly home, and 1-yr mortality was 86%.
Conclusion
The ProVent probability model is a simple and reproducible model that can accurately identify patients requiring prolonged mechanical ventilation who are at high risk of 1-yr mortality.
doi:10.1097/CCM.0b013e3182387d43
PMCID: PMC3395423  PMID: 22080643
communication; critical care; mechanical ventilation; multiple organ failure; outcomes; prognosis
25.  Early Identification of Patients at Risk of Acute Lung Injury 
Rationale: Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies.
Objectives: To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS).
Methods: In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions.
Measurements and Main Results: Twenty-two hospitals enrolled 5,584 patients at risk. ALI developed a median of 2 (interquartile range 1–4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80 (95% confidence interval, 0.78–0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9–5.7).
Conclusions: ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies.
Clinical trial registered with www.clinicaltrials.gov (NCT00889772).
doi:10.1164/rccm.201004-0549OC
PMCID: PMC3056224  PMID: 20802164
respiratory distress syndrome, adult; prevention; prediction model; acute respiratory failure

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