A perspective on the role of uncertainty in sustainability science and engineering.

The Trans-Atlantic Research and Development Interchange on Sustainability Workshop (TARDIS) is a meeting on scientific topics related to sustainability. The 2019 workshop theme was "On the Role of Uncertainty in Managing the Earth for Global Sustainability." This paper presents the perspectives on this topic derived from talks and discussions at the 2019 TARDIS workshop. There are four kinds of uncertainties encountered in sustainability ranging from clear enough futures to true surprises. The current state-of-the-art in assessing and mitigating these uncertainties is discussed.

Body Temperature Modulates Infarction Growth following Endovascular Reperfusion.

BACKGROUND AND PURPOSE: The neuronal substrate is highly sensitive to temperature elevation; however, its impact on the fate of the ischemic penumbra has not been established. We analyzed interactions between temperature and penumbral expansion among successfully reperfused patients with acute ischemic stroke, hypothesizing infarction growth and worse outcomes among patients with fever who achieve full reperfusion. MATERIALS AND METHODS: Data from 129 successfully reperfused (modified TICI 2b/3) patients (mean age, 65 ± 15 years) presenting within 12 hours of onset were examined from a prospectively collected acute ischemic stroke registry. CT perfusion was analyzed to produce infarct core, hypoperfusion, and penumbral mismatch volumes. Final DWI infarction volumes were measured, and relative infarction growth was computed. Systemic temperatures were recorded throughout hospitalization. Correlational and logistic regression analyses assessed the associations between fever (>37.5°C) and both relative infarction growth and favorable clinical outcome (90-day mRS of ≤2), corrected for NIHSS score, reperfusion times, and age. An optimized model for outcome prediction was computed by using the Akaike Information Criterion. RESULTS: The median presentation NIHSS score was 18 (interquartile range, 14-22). Median (interquartile range) CTP-derived volumes were: core = 9.6 mL (1.5-25.3 mL); hypoperfusion = 133 mL (84.2-204 mL); and final infarct volume = 9.6 mL (8.3-45.2 mL). Highly significant correlations were observed between temperature of >37.5°C and relative infarction growth (Kendall τ correlation coefficient = 0.24, P = .002). Odds ratios for favorable clinical outcome suggested a trend toward significance for fever in predicting a 90-day mRS of ≤2 (OR = 0.31, P = .05). The optimized predictive model for favorable outcomes included age, NIHSS score, procedure time to reperfusion, and fever. Likelihood ratios confirmed the superiority of fever inclusion (P < .05). Baseline temperature, range, and maximum temperature did not meet statistical significance. CONCLUSIONS: These findings suggest that imaging and clinical outcomes may be affected by systemic temperature elevations, promoting infarction growth despite reperfusion.

Performance of CT ASPECTS and Collateral Score in Risk Stratification: Can Target Perfusion Profiles Be Predicted without Perfusion Imaging?

BACKGROUND AND PURPOSE: Endovascular trials suggest that revascularization benefits a subset of acute ischemic stroke patients with large-artery occlusion and small-core infarct volumes. The objective of our study was to identify thresholds of noncontrast CT-ASPECTS and collateral scores on CT angiography that best predict ischemic core volume thresholds quantified by CT perfusion among patients with acute ischemic stroke. MATERIALS AND METHODS: Fifty-four patients with acute ischemic stroke (<12 hours) and MCA/intracranial ICA occlusion underwent NCCT/CTP during their initial evaluation. CTP analysis was performed on a user-independent platform (RApid processing of PerfusIon and Diffusion), computing core infarct (defined as CBF of <30% normal). A target mismatch profile consisting of infarction core of ≤50 mL was selected to define candidates with acute ischemic stroke likely to benefit from revascularization. RESULTS: NCCT-ASPECTS of ≥9 with a CTA collateral score of 3 had 100% specificity for identifying patients with a CBF core volume of ≤50 mL. NCCT-ASPECTS of ≤6 had 100% specificity for identifying patients with a CBF core volume of >50 mL. In our cohort, 44 (81%) patients had an NCCT-ASPECTS of ≥9, a CTA collateral score of 3, or an NCCT-ASPECTS of ≤6. CONCLUSIONS: Using an NCCT-ASPECTS of ≥9 or a CTA collateral score of 3 best predicts CBF core volume infarct of ≤50 mL, while an NCCT-ASPECTS of ≤6 best predicts a CBF core volume infarct of >50 mL. Together these thresholds suggest that a specific population of patients with acute ischemic stroke not meeting such profiles may benefit most from CTP imaging to determine candidacy for revascularization.

Diagnostic performance of the PTSD checklist and the Vietnam Era Twin Registry PTSD scale.

AIMS: Self-report questionnaires are frequently used in clinical and epidemiologic studies to assess post-traumatic stress disorder (PTSD). A number of studies have evaluated these scales relative to clinician administered structured interviews; however, there has been no formal evaluation of their performance relative to non-clinician administered epidemiologic assessments such as the Composite International Diagnostic Interview (CIDI). We examined the diagnostic performance of two self-report PTSD scales, the PTSD checklist (PCL) and the Vietnam Era Twin Registry (VET-R) PTSD scale, compared to the CIDI. METHODS: Data were derived from a large epidemiologic follow-up study of PTSD in 5141 Vietnam Era Veterans. Measures included the PCL, VET-R PTSD scale and CIDI. For both the PCL and VET-R PTSD scale, ROC curves, areas under the curve (AUC), sensitivity, specificity, % correctly classified, likelihood ratios, predictive values and quality estimates were generated based on the CIDI PTSD diagnosis. RESULTS: For the PCL and VET-R PTSD scale the AUCs were 89.0 and 87.7%, respectively. Optimal PCL cutpoints varied from the 31-33 range (when considering sensitivity and specificity) to the 36-56 range (when considering quality estimates). Similar variations were found for the VET-R PTSD, ranging from 31 (when considering sensitivity and specificity) to the 37-42 range (when considering quality estimates). CONCLUSIONS: The PCL and VET-R PTSD scale performed similarly using a CIDI PTSD diagnosis as the criterion. There was a range of acceptable cutpoints, depending on the metric used, but most metrics suggested a lower PCL cutpoint than in previous studies in Veteran populations.

Prevalence of dislocation after total hip arthroplasty through a posterolateral approach with partial capsulotomy and capsulorrhaphy.

The senior author altered his surgical technique during total hip arthroplasty from capsulectomy and capsulotomy with closure of the external rotator muscles to capsulotomy and capsulorrhaphy. One thousand patients (500 treated with each procedure) were studied retrospectively in order to determine the prevalences of dislocation after surgery with the two different techniques. The prevalence of dislocation was 2.8% after the capsulectomy and capsulotomy, whereas it was 0.6% after the new technique; this was a significant decrease in the rate of dislocation (p < 0.005, [symbol: see text] = 0.10).

Behavioral characterization of dopamine D5 receptor null mutant mice.

To study behavioral functions of the D5 subtype, mice were generated with null mutations in the D5 gene. This 1st behavioral characterization of D5 null mutant mice (D5-/-) indicated normal general health, sensory abilities, and neurological reflexes. Under basal conditions, D5-/- mice were generally normal on locomotor activity, the rotarod test, acoustic startle response, prepulse inhibition, elevated plus-maze, light <--> dark exploration, Morris water maze, and cued and contextual fear conditioning. In the Porsolt forced swim test for antidepressant activity, male D5-/- mice showed lower levels of immobility. D5-/- mice showed some evidence of reduced responses to the hyperactivity-inducing effects of the D1/D5 receptor agonist SKF 81297. The ability of SKF 81297 to disrupt acoustic startle and prepulse inhibition appeared to be attenuated in D5-/- mice. These results suggest that the D5 receptor is not essential for many dopamine-mediated behaviors but may contribute to the pharmacological activation of dopaminergic pathways relevant to exploratory locomotion, startle, and prepulse inhibition.

Impact of a rotating empiric antibiotic schedule on infectious mortality in an intensive care unit.

OBJECTIVE: The development of antibiotic-resistant bacteria is associated with significant morbidity and mortality in critically ill patients. We postulated that quarterly rotation of empirical antibiotics could decrease infectious complications from resistant organisms in an intensive care unit (ICU). DESIGN: Prospective cohort study. SETTING: An ICU at a university medical center. SUBJECTS: All patients admitted to the general, transplant, or trauma surgery services who developed pneumonia, peritonitis, or sepsis of unknown origin. INTERVENTIONS: A 2-yr study consisting of 1 yr of nonprotocol-driven antibiotic use and 1 yr of rotating empirical antibiotic assignment. MEASUREMENTS AND MAIN RESULTS: Over 100 variables were recorded for each infectious episode, including patient characteristics (e.g., Acute Physiology and Chronic Health Evaluation [APACHE] II score, age, comorbidities), infection characteristics (e.g., site, organism), treatment characteristics (e.g., antibiotic, treatment duration) and outcome measures (e.g., mortality, length of stay, antibiotic cost). Of 1456 consecutive admissions to the ICU, 540 episodes of infection were treated. No differences were noted in age, APACHE II score, race, overall antibiotic utilization or duration of therapy between the 2 yrs of study. Outcome analysis revealed significant reductions in the incidence of antibiotic-resistant Gram-positive coccal infections (7.8 infections/100 admissions vs. 14.6 infections/100 admissions, p <.0001), antibiotic-resistant Gram-negative bacillary infections (2.5 infections/100 admissions vs. 7.7 infections/100 admissions, p <.0001), and mortality associated with infection (2.9 deaths/100 admissions vs. 9.6 deaths/100 admissions, p <.0001) during rotation. Logistic regression identified age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06), APACHE II score (OR, 1.06; 95% CI, 1.01-1.13), solid organ transplantation (OR, 9.50; 95% CI, 2.01-52.21), and malignancy (OR, 10.16; 95% CI, 4.11-26.96) as independent predictors of mortality. Antibiotic rotation was an independent predictor of survival (OR 6.27, 95% CI 2.78-14.16). CONCLUSION: Rotation of empirical antibiotic therapy seems to be a promising method to reduce infectious mortality in an ICU.

Implications of 2,457 consecutive surgical infections entering year 2000.

OBJECTIVE: To assess the demographics and characteristics of infections in surgical patients to define areas that deserve emphasis in surgical education. SUMMARY BACKGROUND DATA: As a result of evolving technology and diseases, the complexity of diagnosing and treating infections has increased during the past three decades for all patients, including those treated primarily by surgeons. No comprehensive analysis of these conditions in a single surgical cohort has been recently published. METHODS: The authors conducted a prospective, observational study of all infections occurring on the general and trauma surgery services at a single university hospital during a 3.5-year period. RESULTS: The authors identified 2,457 infections: 608 community-acquired, 1,053 occurring on the wards, and 796 occurring in the intensive care unit. Although dependent on patient location, the most common sites were abdomen, lung, and wound; the most common isolates were Staphylococcus epidermidis, Staphylococcus aureus, and Candida albicans; and the most commonly used antibiotics were ciprofloxacin, vancomycin, and metronidazole. The overall death rate was 13%, ranging from 5% after community-acquired infections to 25% after infections acquired in the intensive care unit. CONCLUSIONS: Most infections treated by surgeons are hospital-acquired. Infections with gram-positive cocci and fungi are common, with pulmonary infections becoming more common. Fluoroquinolones have become important therapeutic agents. Depending on the type of practice, these data should be helpful to direct educational efforts so that surgeons can remain knowledgeable and active in the nonsurgical care of their patients.

Cohort study of fever and leukocytosis as diagnostic and prognostic indicators in infected surgical patients.

The presence of fever and leukocytosis have traditionally been utilized as important diagnostic markers of infection despite some who question their reliability. To examine this point, the role of fever and leukocytosis as diagnostic and prognostic indicators for surgical infections was evaluated. A prospective observational study was performed on all patients with suspected infection in 1997 on the general surgical services at a university hospital. Fever was defined as maximum temperature (Tmax) > or = 38.5 degrees C, and leukocytosis was defined as a white blood cell (WBC) count > or = 11,000/microl. Among all infections, patients presenting with a Tmax > or = 38.5 degrees C were younger (51.3 +/- 1.1 vs. 53.8 +/- 0.9 years, p = 0.005) and had a higher APACHE II score (15.1 +/- 0.5 vs. 11.4 +/- 0.4; p < 0.001). By logistic regression analysis chronic renal insufficiency was associated with a Tmax < 38.5 degrees C [odds ratio (OR) 0.371, 95% confidence interval (CI) 0.195-0.704], and chronic steroid therapy was associated with a WBC count < 11,000/microl (OR 0.556, 95% CI 0.335-0.921). In addition, infected transplant patients were more likely to present with a Tmax < 38.5 degrees C and a WBC count < 11,000/microl (OR 0.195, 95% CI 0.075-0.502). Mortality rates for infected patients with a Tmax < 38.5 degrees C or > 38.5 degrees C were 11.6% and 12.9%, respectively (p < 0.7), and the lengths of stay were 14 +/- 1 and 18 +/- 1 days, respectively (p < 0.03). Mortality rates for patients with a WBC count < 11,000/microl or > 11,000/microl were 4.7% and 18.6%, respectively (p < 0.001), and the lengths of stay were 14 +/- 1 and 19 +/- 1 days, respectively (p < 0.001). In the setting of infection, chronic renal insufficiency and chronic steroid therapy are associated with suppression of fever and leukocytosis, respectively. Transplantation is an independent predictor of infection in patients presenting without fever or leukocytosis. Leukocytosis, but not fever, may be predictive of hospital mortality in infected surgical patients.

Evaluation of the efficacy of extrapolation population modeling to predict the dynamics of Americamysis bahia populations in the laboratory.

An age-classified projection matrix model has been developed to extrapolate the chronic (28-35 d) demographic responses of Americamysis bahia (formerly Mysidopsis bahia) to population-level response. This study was conducted to evaluate the efficacy of this model for predicting the population behavior of A. bahia held (for more than three generations) under controlled laboratory exposure conditions. The research involved the performance of a standard life-cycle test and a multigenerational (greater than three mysid generations, 55 d) assay using A. bahia to experimentally evaluate model predictions regarding population-level risks of chemical exposure. The organic compound para-nonylphenol was chosen as the chemical stressor in assays. This compound is a ubiquitous contaminant and suspected endocrine disruptor. Utilizing data obtained during the standard life-cycle test, aggregate estimates of population growth rate (lambda) and measured p-nonylphenol concentration were used to develop an exposure-response model of population-level effects. These estimates provided the basis of predictions for the long-term dynamics of mysid populations exposed to p-nonylphenol. The veracity of the mysid population model was evaluated through quantitative comparisons of model predictions based on the life-cycle test with dynamics of the experimental populations (multigenerational assay results). The results indicate that the population model was able to project within a few micrograms per liter the concentration where population-level effects would begin to occur (projected 16 micrograms/L from the model vs measured 19 micrograms/L from the multigenerational assay).

Impact of bloodstream infection on outcomes among infected surgical inpatients.

OBJECTIVE: To assess the importance of bloodstream infection (BSI) to outcomes among infected surgical patients. BACKGROUND: Bloodstream infection complicating infection is thought to connote a more serious condition compared with a primary infection alone. The authors recently reported, however, that BSI does not alter outcomes with central venous catheter colonization in the presence of sepsis. The significance of BSI with other infections has been incompletely evaluated. METHODS: Data on all episodes of infection among surgical patients were collected prospectively during a 38-month period at a single hospital, then analyzed retrospectively to determine the independent prognostic value of BSI for all infections by logistic regression analysis, and for abdominal infections and pneumonia using matched control groups. RESULTS: During the study period, 2,076 episodes of infection occurred, including 363 with BSI. Patients with BSI had a greater severity of illness and a greater death rate. After logistic regression, however, BSI did not independently predict death. After matching patients with abdominal infections and pneumonia with BSI to patients without BSI but with a similar site of infection, severity of illness, age, and causative organism, no difference in outcome was seen. CONCLUSIONS: Bloodstream infection is associated with critical illness and death but appears to be a marker of severe primary disease rather than an independent predictor of outcome.

Preexposure of murine macrophages to CpG oligonucleotide results in a biphasic tumor necrosis factor alpha response to subsequent lipopolysaccharide challenge.

Bacterial DNA and synthetic oligonucleotides containing CpG sequences (CpG-DNA and CpG-ODN) provoke a proinflammatory cytokine response (tumor necrosis factor alpha [TNF-alpha], interleukin-12 [IL-12], and IL-6) and increased mortality in lipopolysaccharide (LPS)-challenged mice via a TNF-alpha-mediated mechanism. It was hypothesized that preexposure of macrophages to CpG-ODN would result in an increased TNF-alpha response to subsequent LPS challenge in vitro. Using the murine macrophage cell line RAW 264.7, we demonstrated both a rapid proinflammatory cytokine response (TNF-alpha) and a delayed inhibitory cytokine response (IL-10) with CpG-ODN. Preexposure of macrophages to CpG-ODN for brief periods (1 to 3 h) augmented TNF-alpha secretion and mRNA accumulation following subsequent LPS challenge (1 microg/ml). However, prolonged preexposure to CpG-ODN (6 to 9 h) resulted in suppression of the TNF-alpha protein and mRNA response to LPS. The addition of anti-IL-10 antibody to CpG-ODN during preexposure resulted in an increase in the LPS-induced TNF-alpha response over that induced by CpG-ODN preexposure alone. Thus, while brief preexposure of macrophages to CpG-ODN augments the proinflammatory cytokine response to subsequent LPS challenge, prolonged preexposure elicits IL-10 production, which inhibits the TNF-alpha response. Although the initial proinflammatory effects of CpG-DNA are well established, the immune response to CpG-DNA may also include autocrine or paracrine feedback mechanisms, leading to a complex interaction of proinflammatory and inhibitory cytokines.

Characteristics of infectious complications associated with mortality after solid organ transplantation.

Infection remains a common source of morbidity and mortality after solid organ transplantation. The purpose of this study was to characterize the continuously changing patterns of post-transplantation infections, analyze early post-transplantation infections, and evaluate characteristics associated with mortality. A secondary analysis was performed on prospectively collected data for all episodes of infection occurring between 10 December 1996 and 28 October 1998 on the surgery services at a university medical center. Post-transplantation infections were compared with those in non-transplantation patients randomly matched by severity of illness. Further analysis was performed on post-transplantation infections occurring during the admission of transplantation compared with those in subsequent admissions. To evaluate factors associated with mortality, episodes occurring in survivors and non-survivors were compared. The results demonstrated that infections in transplantation recipients (n = 303) were associated with a younger age and had significantly lower white blood cell counts (WBC) compared with non-transplantation patients. There was no difference in mortality (15.5 vs. 16.5%, p = 0.74). Post-transplantation infectious complications during the initial hospitalization (n = 105) occurred at 38+/-6 compared with 695+/-66 d (p<0.0001) after transplantation and were associated with a longer length of stay (LOS) and increased mortality (30.5 vs. 7.6%, p<0.0001) compared with those occurring in subsequent admissions (n = 198). Although multiple characteristics of post-transplantation infections were associated with mortality, only the Acute Physiology and Chronic Health Evaluation (APACHE) II score was an independent predictor of mortality. Post-transplantation infections remain a significant source of morbidity and mortality. The leukocyte response to infection was suppressed in the transplantation population. Post-transplantation infections which occur during the admission for transplantation have a markedly increased mortality.

Imaginary companions of preschool children.

The developmental significance of preschool children's imaginary companions was examined. Mothers of 78 children were interviewed about their children's social environments and imaginary companions (if their children had them). Results revealed differences between invisible companions and personified objects (e.g., stuffed animals or dolls) in terms of the pretend friends' stability and ubiquity, identity, and relationship with the child. Relationships with invisible companions were mostly described as sociable and friendly, whereas personified objects were usually nurtured. Mothers reported that personification of objects frequently occurred as a result of acquiring a toy, whereas invisible friends were often viewed as fulfilling a need for a relationship. Compared to children without imaginary companions, children with imaginary companions were more likely to be firstborn and only children.

Bacteremia associated with central venous catheter infection is not an independent predictor of outcomes.

BACKGROUND: Infection is the leading complication of central venous catheters. In the setting of suspected line infection, the CDC recognizes only catheter-related bloodstream infection but not catheter infection without bacteremia, which is designated "colonization." To evaluate the hypothesis that catheter-related bloodstream infection has worse outcomes than catheter infection without bacteremia, we compared demographics, clinical data, and outcomes. STUDY DESIGN: Analysis of catheter infections was performed on data collected prospectively for all episodes of infection occurring from December 1996 to September 1999 on the surgical services at a university hospital. Catheter tips were cultured only when infection was suspected. Catheter infection without bacteremia was defined as systemic evidence of infection, the presence of at least 15 colony-forming units on the catheter tip by a semiquantitative technique, and absence of bloodstream infection with the same organism as the catheter. Catheter-related bloodstream infection required the presence of bacteremia with the same organism as the catheter tip. RESULTS: The 59 patients with catheter-related bloodstream infection had more coexistent infections than the 91 patients with catheter infection without bacteremia (2.9+/-0.1 versus 1.7+/-0.1; p=0.0001), most commonly pneumonia (37.3% versus 16.5%, p = 0.004) and urinary tract infections (28.8% versus 8.8%, p = 0.001). Catheter-related bloodstream infection was associated with an increased proportion of gram-negative organisms compared with catheter infections without bacteremia (29.5% versus 16.9%, p = 0.04) and a trend toward fewer gram-positive organisms (61.5% versus 73.7%, p = 0.07). There were no differences in APACHE II score, WBC, length of hospital stay, time from admission to fever, time from fever to treatment, normalization of WBC, days of antibiotics, defervescence, gender, presence of comorbidities, occurrence of colonization while in an ICU, or mortality rate (18.6% with bacteremia, 24.2% without; p = 0.42). CONCLUSIONS: The presence of bloodstream infection in addition to catheter infection does not appear to alter outcomes. The definition of catheter infection perhaps should be extended to include catheter infections without bloodstream infection in the presence of systemic illness without another source.

Contribution of Escherichia coli alpha-hemolysin to bacterial virulence and to intraperitoneal alterations in peritonitis.

Alpha-hemolysin (Hly) is a common exotoxin produced by Escherichia coli that enhances virulence in a number of clinical infections. The addition of hemolysin production to laboratory bacterial strains is known to increase the lethality of E. coli peritonitis. However, the mechanisms involved have not been determined and the contribution of hemolysin to the alterations in the host intraperitoneal environment and the leukocyte response is not known. Utilizing a rat peritonitis model, we show that wild-type hemolytic E. coli strains have a significant competitive advantage over nonhemolytic strains within the peritoneum. To examine the specific contribution of Hly to E. coli-induced virulence and alterations within the peritoneum, a mixed peritonitis model of E. coli, Bacteroides fragilis, and sterile fecal adjuvant was used. Three transformed E. coli strains were utilized: one strongly secretes active hemolysin (WAF 270), a second secretes active hemolysin but a reduced amount (WAF 260), and the third does not produce hemolysin (WAF 108). After an equal inoculum of each of the three strains, WAF 270 produced a markedly increased lethality and an increased recovery of both E. coli and B. fragilis from the host relative to the other strains. Changes in the intraperitoneal pH, degree of erythrocyte lysis, and recruitment and viability of leukocytes within the peritoneum following the induction of peritonitis differed significantly between the strongly hemolytic and nonhemolytic strains. Induction of peritonitis with WAF 270 caused a pronounced decrease in intraperitoneal pH, lysis of most of the intraperitoneal erythrocytes, and a marked decrease in recoverable viable leukocytes compared to WAF 108. Thus, hemolysin production by E. coli within the peritoneum may alter not only the host's ability to control the hemolytic strain itself but also other organisms.

Extremes of white blood cell count do not independently predict outcome among surgical patients with infection.

Historically patients with severely depressed or elevated white blood cell (WBC) counts during infection were felt to have worse outcomes. To test this assumption we prospectively analyzed all infections on the surgical services at the University of Virginia hospital between December 1, 1996 and April 1, 1999. Among 1737 infectious episodes 59 presented with leukopenia (WBC count < or = 3,000 cells/microL) whereas 66 presented with leukemoid responses (WBC count > or = 30,000 cells/microL). Compared with other infected patients leukopenic patients had higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (18+/-0.9 vs 12+/-0.2, P < 0.0001) and mortality (23.7% vs 11.4%, P = 0.004). Patients with leukemoid responses also had higher APACHE II scores (21+/-1.0 vs 12+/-0.2, P < 0.0001) and mortality (30.3% vs 11.4%, P < 0.0001). Compared with a control group randomly matched (2:1) by age and APACHE II score, however, there was no significant difference in mortality associated with leukopenia or a leukemoid response. Furthermore logistic regression did not reveal leukopenia or leukemoid responses to be independent predictors of mortality (odds ratio for death with leukopenia = 1.57, 95% confidence interval = 0.63-3.91, P = 0.33; odds ratio for death with leukemoid response = 1.19, 95% confidence interval = 0.70-2.02, P = 0.53). Although very low or very high WBC counts may represent markers of severe illness in infected surgical patients they do not appear to be significant contributors to a worsened outcome.

Analysis of aminoglycosides in the treatment of gram-negative infections in surgical patients.

HYPOTHESIS: Antibiotic regimens containing aminoglycosides result in a similar outcome compared with non-aminoglycoside regimens in the treatment of gram-negative infections in surgical patients. DESIGN: An inception cohort study of hospitalized surgical patients from December 1, 1996, through September 30, 1998. Patients were observed from the time of diagnosis of infection to discharge. SETTING: University hospital. PATIENTS: Two hundred fifty-eight consecutive gram-negative infections occurring in general surgical and trauma patients and patients undergoing transplantation. Sixty-six patients received aminoglycosides as a component of their treatment regimen, whereas 192 received other agents. RESULTS: Patients treated with aminoglycosides were younger (mean +/- SEM age, 48+/-2 vs 53+/-1 years; P = .04 by univariate analysis) and had a similar APACHE II (Acute Physiology and Chronic Health Evaluation II) score (mean +/- SEM, 17+/-1 vs 15+/-1; P = .10), yet had a significantly higher mortality vs patients treated with other agents (29% vs 14%; P = .02). A larger proportion of patients requiring hemodialysis were treated with aminoglycosides (33% vs 13%; P = .001). Although there was no difference in the sites of infection between groups, surgical patients with gram-negative pneumonia had a higher mortality when treated with aminoglycosides (37% vs 18%; P = .04), despite similar APACHE II scores (mean +/- SEM, 20+/-1 vs 18+/-1; P = .40). CONCLUSIONS: Despite a younger age and similar severity of illness, patients with gram-negative infections treated with aminoglycosides were associated with a higher mortality rate, although this may be related to selection bias in the use of aminoglycoside agents. The mortality rate associated with gram-negative pneumonia was also higher in patients treated with aminoglycosides, despite a similar severity of illness. Future randomized studies are necessary to reanalyze the role of aminoglycosides in treating surgical patients with gram-negative infections, particularly pneumonia.

Waiting for microbiologic data to direct therapy against nosocomial infections in febrile surgical patients: are outcomes worsened?

HYPOTHESIS: Allowing adequate time for laboratory and culture results before initial treatment may be associated with a worse outcome in nosocomial infections. DESIGN: Cohort study of all episodes of nosocomial infection from December 10, 1996, to October 28, 1998. SETTING: Surgical services at a university hospital. PATIENTS AND METHODS: In surgical patients presenting with fever, 372 episodes of nosocomial infection were evaluated. Nosocomial infections were divided by time from fever to intervention (< or =12, 13-24, and >24 hours). These groups were subdivided by Acute Physiology and Chronic Health Evaluation II (APACHE II) scores into low (< or =10 [n = 114]), moderate (11-20 [n = 169]), and high severity of illness (>20 [n = 89]). Pneumonia and bloodstream infections were divided by APACHE II scores into low (< or =15 [n = 55 and n = 56, respectively]) or high severity of illness (>15 [n = 84 and n = 77, respectively]). MAIN OUTCOME MEASURES: Mortality, length of stay. RESULTS: No difference in outcome was seen between different time intervals from fever to intervention for nosocomial infections in patients with APACHE II scores of no more than 10. Patients treated more than 24 hours after fever were significantly younger than those treated at no more than 12 and 13 to 24 hours with APACHE II scores of 11 to 20 (P<.05) and more than 20 (P<.05). Mortality and length of stay for patients treated at later time intervals were comparable with those of patients treated earlier with similar APACHE II scores. There was no difference in outcome for patients with pneumonia or bloodstream infection. CONCLUSIONS: Episodes of infection in which treatment was withheld until initial microbiologic data were available (24 hours) did not have worse outcomes compared with those treated earlier. Waiting for laboratory and culture results to direct antibiotic therapy for nosocomial infections does not appear harmful and may be potentially beneficial.

Gender-dependent differences in outcome after the treatment of infection in hospitalized patients.

CONTEXT: While it is established that management strategies and outcomes differ by gender for many diseases, its effect on infection has not been adequately studied. OBJECTIVE: To investigate the role of gender among hospitalized patients treated for infection. DESIGN: Observational cohort study conducted during a 26-month period from December 1996 through January 1999. SETTING: University-affiliated hospital. PARTICIPANTS: A total of 892 patients in the surgical units of the hospital with 1470 consecutive infectious episodes (782 in men and 688 in women). MAIN OUTCOME MEASURES: Mortality during hospitalization by gender for infection episodes overall and for specific infectious sites, including lung, peritoneum, bloodstream, catheter, urine, surgical site, and skin/soft tissue. RESULTS: Among all infections, there was no significant difference in mortality based on gender (men, 11.1% vs women, 14.2%; P = .07). After logistic regression analysis, factors independently associated with mortality included higher APACHE (Acute Physiology and Chronic Health Evaluation) II score, older age, malignancy, blood transfusion, and diagnosis of infection more than 7 days after admission, but not gender (female odds ratio [OR] for death, 1.32; 95% confidence interval [CI], 0.90-1.94; P = .16). Mortality was higher in women for lung (men, 18% vs women, 34%; P = .002) and soft tissue (men, 2% vs women, 10%; P < or = .05) infection; for other infectious sites, mortality did not differ by gender. Factors associated with mortality due to pneumonia by logistic regression included higher APACHE II score, malignancy, diabetes mellitus, diagnosis of infection more than 7 days after admission, older age, transplantation, and female gender (OR for death, 2.25; 95% CI, 1.17-4.32; P = .02). CONCLUSIONS: Although gender may not be predictive of mortality among all infections, women appear to be at increased risk for death from hospital-acquired pneumonia, even after controlling for other comorbidities.