The Assignment of American Society of Anesthesiologists Physical Status Classification for Adult Polytrauma Patients: Results From a Survey and Future Considerations.

BACKGROUND: The American Society of Anesthesiologists (ASA) physical status (PS) classification system assesses the preoperative health of patients. Previous studies demonstrated poor interrater reliability and variable ASA PS scores, especially in trauma scenarios. There are few studies that evaluated the assignment of ASA PS scores in trauma patients and no studies that evaluated ASA PS assignment in severely injured adult polytrauma patients. Our objective was to assess interrater reliability and identify sources of discrepancy among anesthesiologists and trauma surgeons in designating ASA PS scores to adult polytrauma patients. METHODS: A link to an online survey containing questions assessing attitudes regarding ASA PS classification, demographic information, and 8 fictional trauma cases was e-mailed to anesthesiologists and trauma surgeons. The participants were asked to assign an ASA PS score to each scenario and explain their choice. Rater-versus-reference and interrater reliability, beyond that expected by chance, among respondents was analyzed using the Fleiss kappa analysis. RESULTS: A total of 349 participants completed the survey. All 8 cases had inconsistent ASA PS scores; several cases had scores ranging from I to VI and variable emergency (E) designations. Using weighted kappa (Kw) analysis for a subset of 201 respondents (101 trauma surgeons [S] and 100 anesthesiologists [A]), we found moderate (Kw = 0.63; SE = 0.024; 95% confidence interval, 0.594-0.666; P < .001) interrater-versus-reference reliability. The interrater reliability was fair (Kw = 0.43; SE = 0.037; 95% confidence interval, 0.360-0.491; P < .001). CONCLUSIONS: This study demonstrates fair interrater reliability beyond that expected by chance of the ASA PS scores among anesthesiologists and trauma surgeons when assessing adult polytrauma patients. Although the ASA PS is used in some trauma risk stratification models, discrepancies of ASA PS scores assigned to trauma cases exist. Future modifications of the ASA PS guidelines should aim to improve the interrater reliability of ASA PS scores in trauma patients. Further studies are warranted to determine the value of the ASA PS score as a trauma prognostic metric.

Improvements in Immune Function and Activation with 48-Week Darunavir/Ritonavir-Based Therapy: GRACE Substudy.

Objective. During the course of HIV infection, progressive immune deficiency occurs. The aim of this prospective substudy was to evaluate the recovery of functional immunity in a subset of patients from the GRACE (Gender, Race, And Clinical Experience) study treated with a DRV/r-based regimen. Methods. The recovery of functional immunity with a darunavir/ritonavir-based regimen was assessed in a subset of treatment-experienced, HIV-1 infected patients from the GRACE study. Results. 19/32 patients (59%) enrolled in the substudy were virologically suppressed (<50 copies/mL). In these patients, median (range) CD4+ cell count increased from 222 (2, 398) cells/mm(3) at baseline to 398 (119, 812) cells/mm(3) at Week 48. CD8+% decreased significantly from baseline to Week 48 (P = .03). Proliferation of CD4+ lymphocytes in response to CD3+/CD28+, phytohemagglutinin, and pokeweed was significantly increased (P < .01) by Week 12. Proliferation in response to Candida and tetanus was significantly increased by Week 48 (P < .01 and P = .014, resp.). Staphylococcal enterotoxin B-stimulated tumor necrosis factor-alpha and interleukin-2 in CD4+ cells was significantly increased by Week 12 (P = .046) and Week 48 (P < .01), respectively. Conclusions. Darunavir/ritonavir-based therapy demonstrated improvements in CD4+ cell recovery and association with progressive functional immune recovery over 48 weeks. This trial is registered with NCT00381303.

Risk factors for extreme events in infants hospitalized for apparent life-threatening events.

OBJECTIVE: To determine whether known risk factors for cardiorespiratory illnesses will help identify infants who could experience extreme events during an admission for an apparent life-threatening event (ALTE) or later at home. STUDY DESIGN: Retrospective cohort study of all patients admitted for ALTE between 1996 and 2006. Extreme events included central apnea >30 seconds, bradycardia >10 seconds, and desaturation >10 seconds at hemoglobin-oxygen saturation value with pulse oximetry <80%. RESULTS: Of the 625 patients included in the study, 46 (7.4%) had extreme cardiorespiratory events recorded, usually within 24 hours of hospital admission. The most frequent diagnosis was upper respiratory tract infection (URTI, 30 infants). These factors increased the likelihood of having extreme events (P < .0001): post-conceptional age <43 weeks (5.2-fold increase), premature birth (6.3-fold), and URTI symptoms (11.2-fold). The most frequent events were extreme desaturations (43/46 infants), preceded by a central apnea. Seven infants had extreme events recorded later during home monitoring (4 with URTI); all 7 infants had sustained extreme events in the hospital. CONCLUSION: Extreme events were identified mostly in association with symptoms of URTIs, in infants born prematurely, and in infants <43 weeks post-conceptional age. Monitoring with a pulse oximeter should identify infants who sustain these events.

Disseminated intravascular coagulation score is associated with mortality for children with shock.

OBJECTIVE: To evaluate the association between disseminated intravascular coagulation (DIC) score and mortality for children with shock. DESIGN: Retrospective. SETTING: Tertiary care, 20-bed pediatric intensive care unit. PATIENTS: A total of 132 children with sepsis or shock admitted from January 2003 to December 2005. MEASUREMENTS AND RESULTS: A total of 132 patients less than 18 years of age with a diagnosis of shock or sepsis were included in the analysis. Of these patients, 90 survived and 42 died (31.8%). Patients ranged from 6 days to 18 years (median 5.8 years), and were a majority male (63%). Variables associated with mortality included peak DIC score within 24 h of ICU admission, age, weight, volume of blood products transfused, inotrope score, pediatric index of mortality (PIM 2) score, 12-h pediatric risk of mortality (PRISM III) score and presence of mechanical ventilation (P < 0.05). Patients with DIC scores >or= 5 (overt DIC) had 50% mortality, compared to 20% for patients with DIC scores < 5. Overall, a one-point rise in DIC score was associated with an increased risk of mortality after adjusting for age, race, gender, hemodynamic instability, and PRISM III score [OR 1.35 (1.02, 1.78)]. Most patients achieve their peak DIC score within 2 h of ICU admission. CONCLUSIONS: This analysis suggests that DIC score, easily calculated early in ICU admission, is associated with mortality for children with sepsis and shock, regardless of initial severity of illness or inotrope use.

Noninvasive monitoring of the autonomic nervous system and hemodynamics of patients with blunt and penetrating trauma.

BACKGROUND: To describe early effects of sympathetic (SNS) and parasympathetic nervous system (PSNS) activities measured by heart rate (HR) and respiratory rate variabilities simultaneously with noninvasive hemodynamic patterns in patients with blunt and penetrating trauma. METHODS: Descriptive study of 168 monitored trauma patients in a level I university-run trauma service. We studied HR and respiratory rate variability by spectral analysis as a measure of autonomic nervous system (ANS) activity in severe blunt and penetrating injuries beginning shortly after their admission to the emergency department. The low frequency area is the area under the HR spectral analysis curve within the frequency range of 0.04 Hz to 0.10 Hz. This area primarily reflects the tone of the SNS as mediated by the vagus nerve. The respiratory frequency area, sometimes referred to as the high frequency area, is a 0.12 Hz-wide frequency range centered around the fundamental respiratory frequency defined by the peak mode of the respiratory activity power spectrum. It is indicative of vagal outflow reflecting PSNS activity. The low frequency area/respiratory frequency area, or L/R ratio, reflects the balance of the SNS and the PSNS. ANS was studied simultaneously with noninvasive hemodynamic patterns after blunt and penetrating thoracic or abdominal injury beginning shortly after admission. We measured cardiac index by bioimpedance, HR, and mean arterial pressure (MAP) to evaluate cardiac function, pulse oximetry (SapO2) to reflect changes in respiratory function, and transcutaneous oxygen indexed to fractional inspired oxygen (PtcO2/FIO2) to reflect tissue perfusion. RESULTS: ANS activity markedly increased especially in the nonsurvivors at 12 hours to 24 hours after admission. Compared with survivors, the nonsurvivors had lower MAP, CI, and PtcO2/FIO2 values associated with increased ANS activity. CONCLUSIONS: In the nonsurvivors, low flow, low MAP, and reduced tissue perfusion were associated with pronounced increases in PSNS and lesser increases in SNS activity. In the survivors, higher CI, MAP, and PtcO2/FIO2 values were associated with lesser increases in both PSNS and SNS activities.

Weaning children from mechanical ventilation with a computer-driven system (closed-loop protocol): a pilot study.

OBJECTIVE: To evaluate the applicability, tolerance, and efficacy of a closed-loop protocol to wean children from mechanical ventilation. DESIGN: Prospective single-center pilot study. SETTING: Tertiary care university hospital. PATIENTS: Twenty mechanically ventilated children aged between 1 and 17 yrs, with a body weight > or =10 kg, no inotropes, and no heavy sedation. INTERVENTIONS: Patients were weaned in pressure support mode by a closed-loop computerized protocol (closed-loop protocol) that interprets clinical data in real time and controls pressure support levels. MEASUREMENTS AND MAIN RESULTS: The closed-loop protocol applicability and tolerance were evaluated. The efficacy of this protocol was evaluated by comparing the duration of mechanical ventilation with a historical group of 20 patients weaned with a clinician-decision protocol. The closed-loop protocol successfully decreased pressure support ventilation in 16 children, recommended separation from the ventilator in 14 children, and did not cause any serious adverse events. Mechanical ventilation duration was 5.1 +/- 4.2 days in the closed-loop group and 6.7 +/- 11.5 days (mean +/- sd) in the clinician-decision group (p = .33) with no difference in the need for reintubation or noninvasive mechanical ventilation (one of 20 and four of 20, respectively; p = .20). CONCLUSIONS: A closed-loop protocol was successfully used to wean children from mechanical ventilation. Further studies are required to assess the impact of this novel therapeutic strategy on the length of mechanical ventilation.

Impulse oscillometry: reference values in children 100 to 150 cm in height and 3 to 10 years of age.

OBJECTIVES: To generate reference equations in North American children to be used for assessing respiratory function through the forced oscillation (Rfo) technique, and to determine the changes in oscillatory resistance, reactance, and resonant frequency (Fres) in relation to age, body height, and weight. DESIGN/SETTING: A prospective cross-sectional study performed on healthy children selected according to strict criteria of American Thoracic Society and European Respiratory Society recommendations. MEASUREMENTS: Triplicate measures were obtained of resistance and reactance at 5, 10, 15, 20, 25, and 35 Hz as well as Fres through the impulse oscillometer (MasterScreen IOS; Jaeger/Toennies; Höchberg, Germany). Two hundred twenty-two white children--normally distributed within the 3- to 10-year age range and 100 to 150 cm in height--were recruited in Montreal, Canada. We used regression analysis to generate multiple predictive equations separately per gender and frequency on age, height, and body weight. RESULTS: Stepwise multiple regression in both natural and logarithmic forms for height, weight, age, and gender showed that standing height was the only significant predictor for all variables. Minimal variability was noted in each subject among the triplicate measurements (p = 0.68 to 0.96). Coherence was > 0.9 at all oscillating frequencies except 5 Hz (< 0.72), with tendencies to lower values in young children. CONCLUSIONS: Resistance and Fres decrease by height, but also by age; and reactance increases. As opposed to our past experience with spirometry in compatible age groups, the Rfo technique was well accepted by preschool children.

Human immunodeficiency virus (HIV)-specific gamma interferon secretion directed against all expressed HIV genes: relationship to rate of CD4 decline.

Immune responses to human immunodeficiency virus (HIV) are detected at all stages of infection and are believed to be responsible for controlling viremia. This study seeks to determine whether gamma interferon (IFN-gamma)-secreting HIV-specific T-cell responses influence disease progression as defined by the rate of CD4 decline. The study population consisted of 31 subjects naive to antiretroviral therapy. All were monitored clinically for a median of 24 months after the time they were tested for HIV-specific responses. The rate of CD4+-T-cell loss was calculated for all participants from monthly CD4 counts. Within this population, 17 subjects were classified as typical progressors, 6 subjects were classified as fast progressors, and 8 subjects were classified as slow progressors. Peripheral blood mononuclear cells were screened for HIV-specific IFN-gamma responses to all expressed HIV genes. Among the detected immune responses, 48% of the recognized peptides were encoded by Gag and 19% were encoded by Nef gene products. Neither the breadth nor the magnitude of HIV-specific responses correlated with the viral load or rate of CD4 decline. The breadth and magnitude of HIV-specific responses did not differ significantly among typical, fast, and slow progressors. These results support the conclusion that although diverse HIV-specific IFN-gamma-secreting responses are mounted during the asymptomatic phase, these responses do not seem to modulate disease progression rates.

Assessment of chemical libraries for their druggability.

High throughput virtual screening is acknowledged as the initial means for identifying hit compounds that will be eventually transformed to leads or drug candidates. To improve quality of screening, it is essential to have powerful methods for the analysis of the compound databases. For this purpose, we have developed a novel and practical scoring function to assess the druggability of compounds. The proposed function consists of 12 metrics that take into account physical, chemical and structural properties as well as the presence of undesirable functional groups. We have applied this 12-metric scoring function to 44 different databases that include more than 3.8 million compounds, which are commercially available. The overall quality of each database was evaluated according to the score and rank measured by our 12-metric function. Our findings suggest that, the majority of compounds that do not satisfy druggable rules do so due to high molecular weight, high logP values and the presence of reactive functional groups.

Neural network-longitudinal assessment of the Electronic Anti-Retroviral THerapy (EARTH) cohort to follow response to HIV-treatment.

HIV infection is for the most part a chronic and asymptomatic disease. To properly monitor the health status of infected individuals it is important to use host and viral surrogate markers as well as pharmacokinetic parameters. Disease progression, assessment of the antiviral potency of the drugs and response to therapy can only be monitored by repetitive measures of viral and host parameters. To prevent the emergence of antiviral drug-resistance, long term side effects and to decide on the appropriate treatment choices, a comprehensive assessment of all contributing factors, medical and non-medical, is necessary. However, the relationship between treatment outcomes with disease markers and other contributing factors is not simple. To date, a model that accurately predicts the likelihood of disease progression or treatment failure in HIV infected patients does not exist. Extending our previous work in this area, we developed temporal Artificial Intelligence models based on Jordan-Elman networks to longitudinally follow viral surrogate markers together with demographics, biochemical and laboratory data to describe the drug-virus-host interactions in over 4000 HIV adult patients. In an international (multi-continent) study of HIV clinical and laboratory data, the profiles of drug-naïve as well as treated patients were evaluated during a 20 year follow-up. Validation of models on a subset of this cohort (n=595) estimated the sensitivity and specificity of treatment success/failure, under different management modalities for individual patients. ROC-curves predicted: virologic success from baseline (ROC=0.871) in drug-naïve previously non-treated patients, switch from virologic success/ failure to failure/success if ever and when (ROC=0.625), switch to virologic success/failure from failure/success within 6 months (ROC=0.722) following a previous switch. This tool may be helpful in the design of longitudinal clinical trials.

Acoustic reflectance of pharyngeal structures in children.

The aim of this study was to examine whether Eccovision Reflectance Pharyngometer could assess the anatomical structure of the upper airway in young children. Secondary aims were to assess changes in pharyngeal volume in children with tonsillar (Group A, n=13) and adenoidal hypertrophy (Group B, n=17) at pre- and post- surgical procedures, respectively and further compare them to children who underwent myringotomy (Control Group C, n=10). In all 40 children (aged 3-9 years, median 6 years) enrolled in this pilot prospective study, six recordings (equally dispersed at pre- and 3 month post- operation per subject) of the pharyngeal cavity along with demographic (age, gender), somatic (standing and sitting height, body weight, head and neck circumference) and anatomic (bimaxilliary and bregma) characteristics, were captured. No significant intra-subject variability was noted within the multiple measurements of the pharyngeal volume at pre- as well as post-incision (ANOVA, P>0.1) in all groups. However, in Group A there was a marked increase from pre- to post-pharyngeal volumes in males (P=0.007), which was not observed in females (P=0.13). In Group B pharyngeal volumes decreased from pre- to post- in both males (P=0.87) and females (P=0.34). On the contrary, in Group C there was no change in pharyngeal volumes. These findings contradicted the visual evaluation of the size of the removed tonsillar and/or adenoidal mass in the first two groups and thus suggested that Eccovision Pharyngometer does not reliably assess pharyngeal volumes in a pediatric population.