Validation Study of an Automated Electronic Acute Lung Injury Screening Tool

Objective

The authors designed an automated electronic system that incorporates data from multiple hospital information systems to screen for acute lung injury (ALI) in mechanically ventilated patients. The authors evaluated the accuracy of this system in diagnosing ALI in a cohort of patients with major trauma, but excluding patients with congestive heart failure (CHF).

Design

Single-center validation study. Arterial blood gas (ABG) data and chest radiograph (CXR) reports for a cohort of intensive care unit (ICU) patients with major trauma but excluding patients with CHF were screened prospectively for ALI requiring intubation by an automated electronic system. The system was compared to a reference standard established through consensus of two blinded physician reviewers who independently screened the same population for ALI using all available ABG data and CXR images. The system's performance was evaluated (1) by measuring the sensitivity and overall accuracy, and (2) by measuring concordance with respect to the date of ALI identification (vs. reference standard).

Measurements

One hundred ninety-nine trauma patients admitted to our level 1 trauma center with an initial injury severity score (ISS) ≥ 16 were evaluated for development of ALI in the first five days in an ICU after trauma.

Main Results

The system demonstrated 87% sensitivity (95% confidence interval [CI] 82.3-91.7) and 89% specificity (95% CI 84.7-93.4). It identified ALI before or within the 24-hour period during which ALI was identified by the two reviewers in 87% of cases.

Conclusions

An automated electronic system that screens intubated ICU trauma patients, excluding patients with CHF, for ALI based on CXR reports and results of ABGs is sufficiently accurate to identify many early cases of ALI.     

Pro-apoptotic low-density lipoprotein subfractions in type II diabetes

OBJECTIVE: To test the hypothesis that differences in subfractions of circulating lipoproteins between diabetic and non-diabetic subjects exist and might contribute to the increased risk for atherosclerosis in type II diabetics. METHODS AND RESULTS: LDL isolated from diabetic (D) and control subjects (N) were separated by FPLC into five subfractions (L1-L5). The fractional distributions of N- and D-LDL were not different, but the most strongly retained subfractions of D-LDL (D-L5) were markedly more pro-apoptotic to bovine aortic endothelial cells in vitro than were the other subfractions in D- or N-LDL. D-L5 induced time- and concentration-dependent apoptosis that was inhibited by z-VAD-fmk. The most electronegative D-LDL subfractions contained substantial amounts of apoproteins AI, E and CIII, higher concentrations of non-esterified fatty acids and LpPLA2, and lower trinitrobenzenesulfonic acid (TNBSA) reactivities. Electronegative subfractions of D-LDL exhibited longer lag times and lower net increases in absorbance at 234 nm with Cu-catalyzed oxidation in vitro. CONCLUSIONS: The toxicities of electronegative subfractions of LDL from diabetic subjects to endothelial cells in vitro may be pivotal to vascular complications of diabetes in vivo, but the specific molecular alterations responsible for the toxicities of these subfractions of diabetic LDL are not known.     

Pretravel Health Preparation Among US Residents Traveling to India to VFRs: Importance of Ethnicity in Defining VFRs

Background.  International travelers visiting friends and relatives (VFRs) in lower income countries experience high rates of travel-related infections. We examined demographic characteristics and pretravel preparation practices among US residents traveling to India to determine factors that may contribute to higher infection rates and that would allow for improved prevention strategies.
Methods.  A cross-sectional study was conducted among US residents traveling to India in departure areas for flights to India at three US international airports during August 2005. Eligible travelers were US residents going to India who were English speaking and ≥18 years. Self-administered questionnaires were used to assess knowledge of and compliance with pretravel health recommendations.
Results.  Of 1,574 eligible travelers, 1,302 (83%) participated; 60% were male and the median age was 37. Eighty-five percent were of South Asian/Indian ethnicity and 76% reported VFR as the primary reason for travel. More than 90% of VFRs had at least a college education and only 6% cited financial barriers as reasons for not obtaining travel health services. VFRs were less likely than non-VFR travelers to seek pretravel health advice, to be protected against hepatitis A or typhoid fever, and less likely to be taking appropriate antimalarial chemoprophylaxis. However, when stratified by ethnicity, travelers of South Asian ethnicity were less likely than other travelers to adhere to pretravel health recommendations, regardless of VFR status.
Conclusions.  Similar to previous studies, VFR status was associated with pretravel health practices that leave travelers at risk for important infectious diseases. This association differed by ethnicity, which may also be an important marker of nonadherence to pretravel health recommendations. These findings have important implications for identifying at-risk travelers and properly targeting prevention messages.     

Development of a base set of toxicity tests using ultrafine TiO2 particles as a component of nanoparticle risk management

The development of a risk management system for nanoscale or ultrafine particle-types requires a base set of hazard data. Assessing risk is a function of hazard and exposure data. Previously, we have suggested "parallel tracks" as a strategy for conducting nanoparticle research. On the one hand, mechanistic studies on "representative" nanoparticles could be supported by governmental agencies. Alternatively, with regard to commercial nanoparticles, the environmental, health and safety (EHS) framework would include a minimum base set of toxicity studies which should be supported by the companies that are developing nano-based products. The minimum base set could include the following criteria: substantial particle characterization, pulmonary toxicity studies, acute dermal toxicity and sensitization studies, acute oral and ocular toxicity studies, along with screening type genotoxicity, and aquatic toxicity studies. We report here the toxicity results of a base set of hazard tests on a set of newly developed, well-characterized, ultrafine TiO(2) (uf-TiO(2)) particle-types. In vivo pulmonary toxicity studies in rats demonstrated low inflammatory potential and lung tissue toxicity. Acute dermal irritation studies in rabbits and local lymph node assay results in mice indicated that uf-TiO(2) was not a skin irritant or dermal sensitizer. Acute oral toxicity studies demonstrated very low toxicity and uf-TiO(2) produced short-term and reversible ocular conjunctival redness in rabbits. Genotoxicity tests demonstrated that uf-TiO(2) was negative in both the bacterial reverse mutation test and in an in vitro mammalian chromosome aberration test with Chinese hamster ovary cells. The results of aquatic toxicity screening studies demonstrated that uf-TiO(2) exhibited low concern for aquatic hazard in unaerated, 48h, static acute tests using the water flea, Daphnia magna; exhibited low concern for aquatic hazard in unaerated, 96h, static acute tests using the rainbow trout, Oncorhynchus mykiss; and exhibited medium concern in a 72h acute test using the green algae Pseudokirchneriella subcapitata. To summarize the findings, the results of most of the studies demonstrated low hazard potential in mammals or aquatic species following acute exposures to the ultrafine TiO(2) particle-types tested in this program.     

Turning subjective into objective: the BCCT.core software for evaluation of cosmetic results in breast cancer conservative treatment

Twelve expert observers from nine different countries convened in a workshop to evaluate the validity of the Breast Cancer Conservative Treatment. Cosmetic results (BCCT.core) software, an objective method for the aesthetic evaluation of breast cancer conservative treatment. Experts were initially asked to subjectively classify the aesthetic results of 30 photographed cases submitted to breast cancer conservative treatment according to the four-point Harris scale. It was pre-established that if at least two-thirds [Cardoso MJ, Cardoso J, Santos AC, Barros H, Oliveira MC. Interobserver agreement and consensus over the esthetic evaluation of conservative treatment for breast cancer. Breast 2005] of participants provided the same classification this would be considered a consensual evaluation for that case. For cases where such agreement was not reached, consensus was obtained using a nominal group technique. Experts then individually performed objective evaluation of the same set of photographs using the BCCT.core software. This provides an automatic rating of aesthetic results, once scale and reference points in the photograph have been chosen. Agreement between observers, between each observer and the consensus, for computer evaluation obtained by the different participants and between software and consensus was calculated using multiple kappa (k) and weighted kappa (wk) statistics. In the subjective assessment, first-round consensus was achieved in 17 (57%) cases. Overall interobserver agreement was fair to moderate (k=0.40, wk=0.57). In the objective assessment there was a higher level of concordance between participants (k=0.86, wk=0.90). Agreement between software and consensus classification was fair (k=0.34, wk=0.53), but was higher in the 17 cases that reached first-round consensus (k=0.60, wk=0.73). Merging the two middle classes of the Harris scale, to form a three-point scale, led to an improvement of all non-weighted measures of agreement. These results show that the BCCT.core software provides consistent evaluation of cosmesis. It has the potential to become a gold standard method for assessment of breast cosmesis in clinical trials, as it can be used simultaneously by a panel of observers from different parts of the world to provide more reliable assessments than has been possible previously.