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OBJECTIVE: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals following the use of plague as a biological weapon against a civilian population. PARTICIPANTS: The working group included 25 representatives from major academic medical centers and research, government, military, public health, and emergency management institutions and agencies. EVIDENCE: MEDLINE databases were searched from January 1966 to June 1998 for the Medical Subject Headings plague, Yersinia pestis, biological weapon, biological terrorism, biological warfare, and biowarfare. Review of the bibliographies of the references identified by this search led to subsequent identification of relevant references published prior to 1966. In addition, participants identified other unpublished references and sources. Additional MEDLINE searches were conducted through January 2000. CONSENSUS PROCESS: The first draft of the consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group was convened to review drafts of the document in October 1998 and May 1999. The final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members. CONCLUSIONS: An aerosolized plague weapon could cause fever, cough, chest pain, and hemoptysis with signs consistent with severe pneumonia 1 to 6 days after exposure. Rapid evolution of disease would occur in the 2 to 4 days after symptom onset and would lead to septic shock with high mortality without early treatment. Early treatment and prophylaxis with streptomycin or gentamicin or the tetracycline or fluoroquinolone classes of antimicrobials would be advised.

Context Despite the best efforts of health care practitioners, medical errors are inevitable. Disclosure of errors to patients is desired by patients and recommended by ethicists and professional organizations, but little is known about how patients and physicians think medical errors should be discussed. Objective To determine patients' and physicians' attitudes about error disclosure. Design, Setting, and Participants Thirteen focus groups were organized, including 6 groups of adult patients, 4 groups of academic and community physicians, and 3 groups of both physicians and patients. A total of 52 patients and 46 physicians participated. Main Outcome Measures Qualitative analysis of focus group transcripts to determine the attitudes of patients and physicians about medical error disclosure; whether physicians disclose the information patients desire; and patients' and physicians' emotional needs when an error occurs and whether these needs are met. Results Both patients and physicians had unmet needs following errors. Patients wanted disclosure of all harmful errors and sought information about what happened, why the error happened, how the error's consequences will be mitigated, and how recurrences will be prevented. Physicians agreed that harmful errors should be disclosed but "choose their words carefully" when telling patients about errors. Although physicians disclosed the adverse event, they often avoided stating that an error occurred, why the error happened, or how recurrences would be prevented. Patients also desired emotional support from physicians following errors, including an apology. However, physicians worried that an apology might create legal liability. Physicians were also upset when errors happen but were unsure where to seek emotional support. Conclusions Physicians may not be providing the information or emotional support that patients seek following harmful medical errors. Physicians should strive to meet patients' desires for an apology and for information on the nature, cause, and prevention of errors. Institutions should also address the emotional needs of practitioners who are involved in medical errors.

OBJECTIVE: To develop consensus-based recommendations for measures to be taken by medical and public health professionals following the use of anthrax as a biological weapon against a civilian population. PARTICIPANTS: The working group included 21 representatives from staff of major academic medical centers and research, government, military, public health, and emergency management institutions and agencies. EVIDENCE: MEDLINE databases were searched from January 1966 to April 1998, using the Medical Subject Headings anthrax, Bacillus anthracis, biological weapon, biological terrorism, biological warfare, and biowarfare. Review of references identified by this search led to identification of relevant references published prior to 1966. In addition, participants identified other unpublished references and sources. CONSENSUS PROCESS: The first draft of the consensus statement was a synthesis of information obtained in the formal evidence-gathering process. Members of the working group provided formal written comments which were incorporated into the second draft of the statement. The working group reviewed the second draft on June 12, 1998. No significant disagreements existed and comments were incorporated into a third draft. The fourth and final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members. CONCLUSIONS: Specific consensus recommendations are made regarding the diagnosis of anthrax, indications for vaccination, therapy for those exposed, postexposure prophylaxis, decontamination of the environment, and additional research needs.

This study meta-analytically examined extensive literature associated with work commitment. The primary purposes were to (a) cumulate correlations among dimensions of work commitment to see which were intercorrelated and (b) determine impact of work commitment dimensions and subdimensions on specific outcome variables (job satisfaction, job performance, turnover intentions, and turnover). Results were cumulated across 997 articles. The positive manifold of correlations suggests the presence of a common psychological construct underlying different commitment forms, with the exception of calculative, continuance, and union commitment. Most of the 94 meta-analyzed correlations were small, suggesting that concept redundancy is not a major concern. Meta-analyses of the correlations of 24 commitment constructs with 4 outcome variables suggest that different commitment forms have similar patterns of correlations with outcome variables.

OBJECTIVE: To determine the attributable cost of ventilator-associated pneumonia from a hospital-based cost perspective, after adjusting for potential confounders. DESIGN: Patients admitted between January 19, 1998, and December 31, 1999, were followed prospectively for the occurrence of ventilator-associated pneumonia. Hospital costs were defined by using the hospital cost accounting database. SETTING: The medical and surgical intensive care units at a suburban, tertiary care hospital. PATIENTS: Patients requiring >24 hrs of mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured occurrence of ventilator-associated pneumonia, in-hospital mortality rate, total intensive care unit (ICU) and hospital lengths of stay (LOS), and total hospital cost per patient. Ventilator-associated pneumonia occurred in 127 of 819 patients (15.5%). Compared with uninfected, ventilated patients, patients with ventilator-associated pneumonia had a higher Acute Physiology and Chronic Health Evaluation II score on admission (p <.001) and were more likely to require multiple intubations (p <.001), hemodialysis (p <.001), tracheostomy (p <.001), central venous catheters (p <.001), and corticosteroids (p <.001). Patients with ventilator-associated pneumonia were more likely to be bacteremic during their ICU stay (36 [28%] vs. 22 [3%]; p <.001). Patients with ventilator-associated pneumonia had significantly higher unadjusted ICU LOS (26 vs. 4 days; p <.001), hospital LOS (38 vs. 13 days; p <.001), mortality rate (64 [50%] vs. 237 [34%]; p <.001), and hospital costs (70,568 dollars vs. 21,620 dollars, p <.001). Multiple linear regression, controlling for other factors that may affect costs, estimated the attributable cost of ventilator-associated pneumonia to be 11,897 dollars (95% confidence interval = 5,265 dollars-26,214 dollars; p <.001). CONCLUSIONS: Patients with ventilator-associated pneumonia had significantly longer ICU and hospital LOS, with higher crude hospital cost and mortality rate compared with uninfected patients. After we adjusted for underlying severity of illness, the attributable cost of ventilator-associated pneumonia was approximately 11,897 dollars.

OBJECTIVE: To evaluate a clinical guideline for the treatment of ventilator-associated pneumonia. DESIGN: Prospective before-and-after study design. SETTING: A medical intensive care unit from a university-affiliated, urban teaching hospital. PATIENTS: Between April 1999 and January 2000, 102 patients were prospectively evaluated. INTERVENTIONS: Prospective patient surveillance, data collection, and implementation of an antimicrobial guideline for the treatment of ventilator-associated pneumonia. MEASUREMENTS AND MAIN RESULTS: The main outcome evaluated was the initial administration of adequate antimicrobial treatment as determined by respiratory tract cultures. Secondary outcomes evaluated included the duration of antimicrobial treatment for ventilator-associated pneumonia, hospital mortality, intensive care unit and hospital lengths of stay, and the occurrence of a second episode of ventilator-associated pneumonia. Fifty consecutive patients with ventilator-associated pneumonia were evaluated in the before period and 52 consecutive patients with ventilator-associated pneumonia were evaluated in the after period. Severity of illness using Acute Physiology and Chronic Health Evaluation II (25.8 +/- 5.7 vs. 25.4 +/- 8.1, p =.798) and the clinical pulmonary infection scores (6.6 +/- 1.0 vs. 6.9 +/- 1.2, p =.105) were similar for patients during the two treatment periods. The initial administration of adequate antimicrobial treatment was statistically greater during the after period compared with the before period (94.2% vs. 48.0%, p <.001). The duration of antimicrobial treatment was statistically shorter during the after period compared with the before period (8.6 +/- 5.1 days vs. 14.8 +/- 8.1 days, p <.001). A second episode of ventilator-associated pneumonia occurred statistically less often among patients in the after period (7.7% vs. 24.0%, p =.030). CONCLUSIONS: The application of a clinical guideline for the treatment of ventilator-associated pneumonia can increase the initial administration of adequate antimicrobial treatment and decrease the overall duration of antibiotic treatment. These findings suggest that similar types of guidelines employing local microbiological data can be used to improve overall antibiotic utilization for the treatment of ventilator-associated pneumonia.

OBJECT: The objective of this study was to identify specific independent risk factors for surgical site infections (SSIs) occurring after laminectomy or spinal fusion. METHODS: The authors performed a retrospective case-control study of data obtained in patients between 1996 and 1999 who had undergone laminectomy and/or spinal fusion. Forty-one patients with SSI or meningitis were identified, and data were compared with those acquired in 178 uninfected control patients. Risk factors for SSI were determined using univariate analyses and multivariate logistic regression. The spinal surgery-related SSI rate (incisional and organ space) during the 4-year study period was 2.8%. Independent risk factors for SSI identified by multivariate analysis were postoperative incontinence (odds ratio [OR] 8.2, 95% confidence interval [CI] 2.9-22.8), posterior approach (OR 8.2, 95% CI 2-33.5), procedure for tumor resection (OR 6.2, 95% CI 1.7-22.3), and morbid obesity (OR 5.2, 95% CI 1.9-14.2). In patients with SSI the postoperative hospital length of stay was significantly longer than that in uninfected patients (median 6 and 3 days, respectively; p < 0.001) and were readmitted to the hospital for a median additional 6 days for treatment of their infection. Repeated surgery due to the infection was required in the majority (73%) of infected patients. CONCLUSIONS: Postoperative incontinence, posterior approach, surgery for tumor resection, and morbid obesity were independent risk factors predictive of SSI following spinal surgery. Interventions to reduce the risk for these potentially devastating infections need to be developed.

BACKGROUND: The bispectral (BIS) index has previously been shown to be a quantifiable measure of the sedative and hypnotic effects of anesthetic drugs. This study was designed to assess the effect of BIS monitoring on the utilization of volatile anesthetics and their recovery profiles after ambulatory surgery. METHODS: Sixty consenting women undergoing outpatient laparoscopic tubal ligation procedures were randomly assigned to one of four treatment groups. After a standardized induction, anesthesia was maintained with either desflurane (Groups I and II) or sevoflurane (Groups III and IV) in combination with nitrous oxide, 65%, and fentanyl. In the control groups (Groups I and III), the anesthesiologists were blinded to the BIS value, and the volatile anesthetics were administered according to standard clinical practice. In Groups II and IV, the volatile anesthetics were titrated to maintain the BIS value at 60. The volatile anesthetic usage and the times from discontinuation of anesthesia to verbal response, orientation, and home-readiness were recorded. RESULTS: During the maintenance period, the BIS values were significantly lower in the control groups (mean, 42) compared with the BIS-titrated groups (mean, 60). The volatile anesthetic usage in the BIS-titrated groups was 30-38% lower (P < 0.05) compared with the control groups. Similarly, the times to verbal responsiveness were 30-55% shorter in the BIS-titrated (vs. control) groups. CONCLUSIONS: Titrating desflurane and sevoflurane using the BIS monitor decreased their utilization and contributed to a faster emergence from anesthesia in outpatients undergoing laparoscopic tubal ligation procedures.

Executive Overview Nonmarket strategy is now well established as a legitimate field of research. In this paper, we review the dominant paradigms in contemporary nonmarket research and report on the key insights and findings from those perspectives. We use this review to suggest that the integration of institutional and strategic perspectives provides a logical path for the continued development of nonmarket strategy research going forward. Looking ahead, our premise is that institutional perspectives will have an increased relevance to nonmarket scholarship, particularly with the increasing importance of emergent economies to international business. As companies are required to invest more in nonmarket practices, and adapt those practices to unique country contexts, we anticipate that research will increasingly draw from multiple conceptual paradigms and perspectives.

Although transcription and pre-mRNA processing are colocalized in eukaryotic nuclei, molecules linking these processes have not previously been described. We have identified four novel rat proteins by their ability to interact with the repetitive C-terminal domain (CTD) of RNA polymerase II in a yeast two-hybrid assay. A yeast homolog of one of the rat proteins has also been shown to interact with the CTD. These CTD-binding proteins are all similar to the SR (serine/arginine-rich) family of proteins that have been shown to be involved in constitutive and regulated splicing. In addition to alternating Ser-Arg domains, these proteins each contain discrete N-terminal or C-terminal CTD-binding domains. We have identified SR-related proteins in a complex that can be immunoprecipitated from nuclear extracts with antibodies directed against RNA polymerase II. In addition, in vitro splicing is inhibited either by an antibody directed against the CTD or by wild-type but not mutant CTD peptides. Thus, these results suggest that the CTD and a set of CTD-binding proteins may act to physically and functionally link transcription and pre-mRNA processing.

BACKGROUND: Dexmedetomidine (Dex), an alpha(2) agonist, has well-known anesthetic and analgesic-sparing effects. We designed this prospective, randomized, double-blind, and placebo-controlled dose-ranging study to evaluate the effect of Dex on both early and late recovery after laparoscopic bariatric surgery. METHODS: Eighty consenting ASA II-III morbidly obese patients were randomly assigned to 1 of 4 treatment groups: (1) control group received a saline infusion during surgery, (2) Dex 0.2 group received an infusion of 0.2 microg x kg(-1) x h(-1) IV, (3) Dex 0.4 group received an infusion of 0.4 microg x kg(-1) x h(-1) IV, and (4) Dex 0.8 group received an infusion of 0.8 microg x kg(-1) x h(-1) IV. Mean arterial blood pressure values were maintained within +/-25% of the preinduction baseline values by varying the inspired desflurane concentration. Perioperative hemodynamic variables, postoperative pain scores, and the need for "rescue" analgesics and antiemetics were recorded at specific intervals. Follow-up evaluations were performed on postoperative days (PODs) 1, 2, and 7 to assess severity of pain, analgesic requirements, patient satisfaction with pain management, quality of recovery, as well as resumption of dietary intake and recovery of bowel function. RESULTS: Dex infusion, 0.2, 0.4, and 0.8 microg x kg(-1) x h(-1), reduced the average end-tidal desflurane concentration by 19, 20, and 22%, respectively. However, it failed to facilitate a significantly faster emergence from anesthesia. Although the intraoperative hemodynamic values were similar in the four groups, arterial blood pressure values were significantly reduced in the Dex 0.2, 0.4, and 0.8 groups compared with the control group on admission to the postanesthesia care unit (PACU) (P < 0.05). The length of the PACU stay was significantly reduced in the Dex groups (81 +/- 31 to 87 +/- 24 vs 104 +/- 33 min in the control group, P < 0.05). The amount of rescue fentanyl administered in the PACU was significantly less in the Dex 0.2, 0.4, and 0.8 groups versus control group (113 +/- 85, 108 +/- 67, and 120 +/- 78 vs 187 +/- 99 microg, respectively, P < 0.05). The percentage of patients requiring antiemetic therapy was also reduced in the Dex groups (30, 30, and 10% vs 70% in the control group). However, the patient-controlled analgesia morphine requirements on PODs 1 and 2 were not different among the four groups. Pain scores in the PACU, and on PODs 1, 2, and 7, in the three Dex groups were not different from the control group. Finally, quality of recovery scores and times to recovery of bowel function and hospital discharge did not differ among the four groups. CONCLUSIONS: Adjunctive use of an intraoperative Dex infusion (0.2-0.8 microg x kg(-1) x h(-1)) decreased fentanyl use, antiemetic therapy, and the length of stay in the PACU. However, it failed to facilitate late recovery (e.g., bowel function) or improve the patients' overall quality of recovery. When used during bariatric surgery, a Dex infusion rate of 0.2 microg x kg(-1) x h(-1) is recommended to minimize the risk of adverse cardiovascular side effects.

BACKGROUND: An increase in incidence of ductal carcinoma in situ (DCIS) of the breast has been documented, and concerns regarding overly aggressive treatment have been raised. This study was designed to evaluate the use of surgery and radiation therapy in treating DCIS. METHODS: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results database to assess treatment of patients with DCIS with no evidence of microinvasion who were diagnosed from January 1, 1992, through December 31, 1999. We assessed the rates of mastectomy, breast reconstruction, radiation therapy after lumpectomy, and axillary dissection. Associations were analyzed by logistic regression. RESULTS: During the study period, 25 206 patients met selection criteria. The incidence of DCIS dramatically increased with time; however, the incidence of comedo lesions did not change. The rate of mastectomy decreased from 43% in 1992 to 28% in 1999, after controlling for age, race, tumor size, comedo histology, and geographic location. However, because of the increase in the diagnosis of DCIS, the age-adjusted incidence of mastectomy for DCIS in the population did not change (7.8 per 100 000 women in 1992 and 1999). Almost half the patients undergoing lumpectomy did not undergo radiation therapy (55% in 1992 and 46% in 1999); in those with comedo histology, 33% did not undergo radiation therapy after lumpectomy, even in 1999. Overall, patients were less likely to have axillary dissection over time (34% in 1992 versus 15% in 1999), yet the rate of axillary dissection was still high (30%) in patients undergoing mastectomy in 1999. Large, statistically and clinically significant variation by geographic location was found in treatment. CONCLUSIONS: Treatment of DCIS changed in a clinically significant fashion between 1992 and 1999. Throughout this study, many patients were found to undergo aggressive surgical therapy, including mastectomy and axillary dissection, whereas others appeared to be undertreated, e.g., not receiving radiation therapy after lumpectomy, even in the presence of adverse histologic features. Variation in demographic and geographic factors indicates that at least some of these treatment differences reflect individual and institutional practice patterns that may be modifiable.

BACKGROUND: Cigarette smoking is an established risk factor for colorectal cancer. Because colorectal carcinogenesis is a heterogeneous process, we investigated whether cigarette smoking is differentially associated with molecularly defined subtypes of colorectal cancer. METHODS: We evaluated associations between smoking and incident colorectal cancer, overall and by microsatellite instability (MSI) phenotype (MSI-high vs MSI-low or microsatellite stable), CpG island methylator phenotype (CIMP positive or CIMP negative), and BRAF mutation status (BRAF mutation positive or BRAF mutation negative), among 37 399 participants in a population-based cohort study (the Iowa Women's Health Study). Cigarette smoking (and other exposures) was assessed by self-report at baseline in 1986, including smoking status (never and ever [former or current]), age at initiation, total duration, average number of cigarettes smoked per day, cumulative pack-years, and induction period. Vital status and state of residence were determined by mailed follow-up questionnaires in 1987, 1989, 1992, and 1997 and by linkage to Iowa death certificate records. Nonrespondents were checked via the National Death Index to identify descendants. Participants with newly diagnosed (ie, incident) colorectal cancer were identified through annual linkage with the Iowa Cancer Registry. Archived paraffin-embedded tumor tissue specimens were obtained for 555 patients with colorectal cancer who were diagnosed from January 1, 1986, through December 31, 2002, and MSI status, CIMP status, and BRAF status were determined. Multivariable Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Ever-smokers were at moderately increased risk for incident colorectal cancer (RR = 1.19, 95% CI = 1.05 to 1.35) compared with never-smokers. Higher risk estimates were observed for current smokers with MSI-high tumors (RR = 1.99, 95% CI = 1.26 to 3.14), CIMP-positive tumors (RR = 1.88, 95% CI = 1.22 to 2.90), and BRAF mutation-positive tumors (RR = 1.92, 95% CI = 1.22 to 3.02). Other smoking-related variables (ie, age at initiation, total duration, average number of cigarettes smoked per day, cumulative pack-years, and induction period) were also associated with MSI-high, CIMP-positive, and BRAF mutation-positive tumor subtypes. Conversely, cigarette smoking status (ever vs never) was not associated with the MSI-low or microsatellite stable (RR = 1.00, 95% CI = 0.79 to 1.25), CIMP-negative (RR = 1.02, 95% CI = 0.81 to 1.30), or BRAF mutation-negative subtypes (RR = 1.00, 95% CI = 0.65 to 1.27). CONCLUSIONS: In this prospective study of older women, cigarette smoking was associated with the MSI-high, CIMP-positive, and BRAF mutation-positive colorectal cancer subtypes, which indicates that epigenetic modification may be functionally involved in smoking-related colorectal carcinogenesis.

A mathematical theory is presented which when applied to a comparison of the registrars lists of births and deaths with a list obtained in a house-to-house canvass gives an estimate of the total number of events over an area in a specified period. It also gives the extent of registration. Allowance is made for the fact that the chance of an event being missed on 1 list may not be independent of its chance of being missed on the other list. The theory is applied to an enquiry that was conducted in 1947 over an area known as the Singur Health Center near Calcutta covering the years 1945 and 1946 separately. It is found that the estimated total number of events for the area is usually greater when the estimate is built up by summing the totals for individual groups than when it is computed at once for the aggregated population. This observation according to the theory confirms positive dependence and indicates that the greater figure is closer to the truth. The annual number of births and deaths in the Singur Health Center (total population 64000) is estimated subject to a standard error of from 1-3%. The registration is estimated to vary from about 40-70% with a standard error of about 3%. Higher estimates of the number of deaths were obtained under 3 different approaches to subdividing the population into homogeneous groups. Separate calculations were prepared for each of the 4 political subdivisions comprising the Center for each sex separately and for sex and age groups. In each case the separate estimates obtained for the subpopulations were combined to obtain 3 estimates of the number of deaths for the population of the Center as a whole. The largest estimated number of deaths was obtained using the 3rd approach. This suggests that the subdivision into sex and age groups minimized the correlation of events missed in the 2 data collection systems. (summaries in FRE SPA)

The purpose of this study was to determine the impact of a scheduled change of antibiotic classes, used for the empiric treatment of suspected gram-negative bacterial infections, on the incidence of ventilator-associated pneumonia and nosocomial bacteremia. Six hundred eighty patients undergoing cardiac surgery were evaluated. During a 6-mo period (i.e., the before-period), our traditional practice of prescribing a third generation cephalosporin (ceftazidime) for the empiric treatment of suspected gram-negative bacterial infections was continued. This was followed by a 6-mo period (i.e., the after-period) during which a quinolone (ciprofloxacin) was used in place of the third-generation cephalosporin. The incidence of ventilator-associated pneumonia was significantly decreased in the after-period (n = 327) compared with the before-period (n = 353) (6.7 versus 11.6%; p = 0.028). This was primarily due to a significant reduction in the incidence of ventilator-associated pneumonia attributed to antibiotic-resistant gram-negative bacteria (0.9 versus 4.0%; p = 0.013). Similarly, we observed a lower incidence of bacteremia attributed to antibiotic-resistant gram-negative bacteria in the after-period compared with the before-period (0.3 versus 1.7%; p = 0.125). These data suggest that a scheduled change of antibiotic classes can reduce the incidence of ventilator-associated pneumonia attributed to antibiotic-resistant gram-negative bacteria.

(1993). Enhancing Statistical Literacy: Enriching Our Society. Journal of the American Statistical Association: Vol. 88, No. 421, pp. 1-8.

OBJECTIVES: To determine the rates, risk factors, and outcomes of ventilator-associated pneumonia in pediatric intensive care unit (PICU) patients. METHODS: A prospective cohort study was conducted at the St Louis Children's Hospital PICU on all patients who were admitted to the PICU from September 1, 1999, to May 31, 2000, except those who died within 24 hours, were > or =18 years of age, or were neonatal intensive care unit patients on extracorporeal membrane oxygenation. The primary outcome measured was the development of ventilator-associated pneumonia. Secondary outcomes were death and hospital and PICU length of stay. Multiple logistic regression analysis was performed to determine independent predictors for ventilator-associated pneumonia. RESULTS: There were 34 episodes of ventilator-associated pneumonia in 30 patients of 911 admissions (3.3%) and 595 (5.1%) mechanically ventilated patients. The mean ventilator-associated pneumonia rate was 11.6/1000 ventilator days. By logistic regression analysis, genetic syndrome (odds ratio [OR]: 2.37; 95% confidence interval [CI]: 1.01-5.46), reintubation (OR: 2.71; 95% CI: 1.18-6.21), and transport out of the PICU (OR: 8.90; 95% CI: 3.82-20.74) independently predicted ventilator-associated pneumonia. CONCLUSIONS: Ventilator-associated pneumonia occurs at significant rates among mechanically ventilated PICU patients and is associated with processes of care. Additional studies are necessary to develop interventions to prevent ventilator-associated pneumonia.

Klarman, Herbert E. Ph.D.; Francis, John O'S. M.B.A.; Rosenthal, Gerald D. Ph.D. Author Information

Ebola viruses cause hemorrhagic disease in humans and nonhuman primates with high fatality rates. These viruses pose a significant health concern worldwide due to the lack of approved therapeutics and vaccines as well as their potential misuse as bioterrorism agents. Although not licensed for human use, recombinant vesicular stomatitis virus (rVSV) expressing the filovirus glycoprotein (GP) has been shown to protect macaques from Ebola virus and Marburg virus infections, both prophylactically and postexposure in a homologous challenge setting. However, the immune mechanisms of protection conferred by this vaccine platform remain poorly understood. In this study, we set out to investigate the role of humoral versus cellular immunity in rVSV vaccine-mediated protection against lethal Zaire ebolavirus (ZEBOV) challenge. Groups of cynomolgus macaques were depleted of CD4+ T, CD8+ T, or CD20+ B cells before and during vaccination with rVSV/ZEBOV-GP. Unfortunately, CD20-depleted animals generated a robust IgG response. Therefore, an additional group of vaccinated animals were depleted of CD4+ T cells during challenge. All animals were subsequently challenged with a lethal dose of ZEBOV. Animals depleted of CD8+ T cells survived, suggesting a minimal role for CD8+ T cells in vaccine-mediated protection. Depletion of CD4+ T cells during vaccination caused a complete loss of glycoprotein-specific antibodies and abrogated vaccine protection. In contrast, depletion of CD4+ T cells during challenge resulted in survival of the animals, indicating a minimal role for CD4+ T-cell immunity in rVSV-mediated protection. Our results suggest that antibodies play a critical role in rVSV-mediated protection against ZEBOV.

Nine commercial dairy herds, each with low herd milk somatic cell counts, were monitored for 1 yr to determine prevalence of intramammary infections and rates of clinical mastitis. Staphylococcus species was the bacterial group most frequently isolated from quarters at calving and at drying off. Environmental streptococci and coliform intramammary infections totaled less than 6% of quarters at both calving and at drying off. Staphylococcus aureus were isolated from less than 1% of quarters and Streptococcus agalactiae from 0% of quarters at both calving and drying off. A total of 646 clinical cases of mastitis were diagnosed in 548 quarters of 406 cows. Mean rate of clinical mastitis among herds was .457 clinical cases/305 cow-days. Rates of clinical mastitis ranged among herds from .273 to .748 clinical cases/305 cow-days. Coliforms and bacteriologically negative and environmental streptococci accounted for 82.3% of clinical cases. Rates of clinical mastitis and severity of clinical signs differed among herds, seasons of the year, parity groups, and stages of lactation. Rates of clinical mastitis were highest during summer, in first lactation cows, and during the first 7 d of lactation.