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Biomedical subjects

William L Jackson

Publications and source records attributed to William L Jackson.

At least 19 recordsLinked to original sources
PubMed2006

Minimizing costs for treating deep vein thrombosis: the role for fondaparinux.

BACKGROUND: Deep vein thrombosis (DVT) remains a major burden and fondaparinux represents a new option for DVT therapy. We sought to determine if fondaparinux offered financial advantages over low-molecular weight heparin since it is given as a fixed dose over a wide range of patient weights rather then dosed directly on weight and because fondaparinux is not associated with heparin-induced thrombocytopenia (HIT). METHODS: We conducted a cost-minimization analysis comparing fondaparinux to enoxaparin for acute anticoagulation in DVT. We modeled a cohort of 1,000 hypothetical subjects and drew estimates for model inputs from the published literature. We completed multiple sensitivity analyses to asses the significance of our assumptions and used Monte Carlo simulation to estimate the 95% confidence intervals (CIs) around our estimation of the cost differential for the two agents. RESULTS: In the base case, total disease management costs per patient with fondaparinux are US 472 dollars compared to 769 dollars with enoxaparin. The 95% CI around this difference ranges from US 48 dollars to US 401 dollars. The model was mildly sensitive to the pharmacy acquisition costs of fondaparinux and enoxaparin which was the major driver of overall costs. Neither the rates of nor costs associated with DVT recurrence, major bleeding, nor HIT substantially affected our observations. Breakeven analysis indicated our findings to be robust over a wide range of likely clinical scenarios. CONCLUSIONS: From the perspective of a healthcare system, fondaparinux use offers an attractive economic alternative to other agents for initial DVT therapy. Expanded reliance on fondaparinux could potentially result in savings.

Body Weight↗
PubMed2006

Update in ventilator-associated pneumonia.

PURPOSE OF REVIEW: Ventilator-associated pneumonia remains an important topic (or subject) in the care of the critically ill. Issues related to ventilator-associated pneumonia are now particularly acute given the continued increase in rates of antimicrobial resistance seen in intensive care units. This review examines the latest literature in this area, including promising approaches to infection prevention and recently developed guidelines to aid clinicians in limiting, identifying and treating ventilator-associated pneumonia. RECENT FINDINGS: Increasingly rigorous and robust studies have shown the enormous cost, morbidity and mortality of infections acquired in the intensive care unit in general and of ventilator-associated pneumonia in particular, and offered potential management options. Specific areas of promise include advances in means of diagnosis, such as appropriate use of bronchoscopy and inflammatory markers, and treatment methods, including short-course treatment regimens and the use of 'de-escalation' as a strategy for antibiotic prescribing. SUMMARY: Recent studies have started to illuminate the full magnitude of the impact of ventilator-associated pneumonia in the intensive care unit and suggest potential measures for intervention. Hopefully, additional work will aid in eventual development of effective preventive, diagnostic and therapeutic strategies that can reliably improve patient outcomes.

Hospital Mortality↗
PubMed2005

Levofloxacin for treatment of ventilator-associated pneumonia: a subgroup analysis from a randomized trial.

Ventilator-associated pneumonia (VAP) remains a significant challenge in critical care. We conducted a secondary analysis of a multicenter, prospective, randomized trial comparing levofloxacin (750 mg iv q24h) with imipenem-cilastatin (500-1000 mg iv q6-8h) for treatment of nosocomial pneumonia and focused on the subgroup of patients with VAP. The study cohort included 222 patients, with half (111) of the patients assigned to each treatment group. The patients in both groups were similar with respect to age, severity of illness, and duration of mechanical ventilation before the onset of VAP. Among the intention-to-treat population, clinical success was achieved in 58.6% of patients receiving levofloxacin, compared with 63.1% of patients receiving imipenem-cilastatin (P=.49; 95% confidence interval for the difference, -8.77% to 17.79%). Microbiological success and 28-day mortality rates were also comparable. Multivariate analysis demonstrated that assignment to antibiotic treatment (i.e., levofloxacin vs. imipenem-cilastatin) was not predictive of outcomes, thus suggesting that the treatment regimens were equivalent. Both levofloxacin and imipenem-cilastatin regimens were well tolerated and had similar adverse event profiles.

Anti-Bacterial Agents↗
PubMed2005

Invasive approaches to the diagnosis of ventilator-associated pneumonia: a meta-analysis.

OBJECTIVE: Ventilator-associated pneumonia remains a major challenge in the intensive care unit. The role for invasive diagnostic methods (e.g., bronchoscopy) remains unclear. We hypothesized that invasive testing would alter antibiotic management in patients with ventilator-associated pneumonia but would not necessarily alter mortality. DESIGN: Meta-analysis of randomized, controlled trials of invasive diagnostic strategies in suspected ventilator-associated pneumonia and a separate pooled analysis of prospective, observational studies of the effect of invasive cultures on antibiotic utilization in ventilator-associated pneumonia. SETTING: NA. PATIENTS: Subjects enrolled in the various clinical trials identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified four randomized, controlled trials that included 628 patients. The overall quality of these studies was moderate (median Jadad score of 5) and there was both clinical and statistical heterogeneity among these trials. Ventilator-associated pneumonia was confirmed bronchoscopically in 44-69% of participants, with Pseudomonas aeruginosa and Staphylococcus aureus being the most frequently isolated pathogens. Most subjects (90.3%) received adequate antibiotics; however, in one trial there was a significant difference between the invasive and noninvasive arms with respect to this factor. Overall, an invasive approach did not alter mortality (odds ratio 0.89, 95% confidence interval 0.56-1.41). Invasive testing, though, affected antibiotic utilization (odds ratio for change in antibiotic management after invasive sampling, 2.85, 95% confidence interval 1.45-5.59). Five prospective observational studies examined invasive testing and included 635 subjects. These reports confirm that invasive sampling leads to modifications in the antibiotic regimen in more than half of patients (pooled estimate for rate of alteration in antibiotic prescription, 50.3%, 95% confidence interval 35.9-64.6%). CONCLUSIONS: Few trials have systematically examined the impact of diagnostic techniques on outcomes for patients suspected of suffering from ventilator-associated pneumonia. Invasive strategies do not alter mortality. Invasive approaches to ventilator-associated pneumonia affect antibiotic use and prescribing.

APACHE↗
PubMed2005

Fluconazole prophylaxis in critically ill surgical patients: a meta-analysis.

OBJECTIVE: To evaluate the impact of fluconazole prophylaxis on the incidence of fungal infections and on mortality among critically ill surgical patients. DESIGN: Meta-analysis of randomized, placebo-controlled trials of fluconazole prophylaxis. PATIENTS: Subjects participating in the clinical trials in this area. MEASUREMENTS AND MAIN RESULTS: We identified four randomized studies comparing fluconazole to placebo for prevention of fungal infections in the surgical intensive care unit (SICU). The studies enrolled 626 patients and used differing dosing regimens of fluconazole. All trials were double-blind and two were multicenter studies. Fluconazole administration significantly reduced the incidence of fungal infections (pooled odds ratio, 0.44; 95% confidence interval, 0.27-0.72; p < .001). However, fluconazole prophylaxis was not associated with a survival advantage (pooled OR for mortality, 0.87; 95% confidence interval, 0.59-1.28; p = NS). Fluconazole did not statistically alter the rate of candidemia, as this was low across the studies and developed in only 2.2% of all participants. Performing a sensitivity analysis and including two additional studies that indirectly examined fluconazole prophylaxis in the critically ill did not change our observations. Data from the reports reviewed were insufficient to allow comment on the impact of fluconazole prophylaxis on resource utilization, the distribution of non-albicans species of Candida, and the emergence of antifungal resistance. Generally, fluconazole appeared to be safe for SICU patients. CONCLUSIONS: Prophylactic fluconazole administration for prevention of mycoses in SICU patients appears to successfully decrease the rate of these infections, but this strategy does not improve survival. The absence of a survival advantage may reflect the few studies in this area and the possibility that this issue has not been adequately studied. Because of the potential for both resistance and emergence of non-albicans isolates, clinicians must consider these issues when evaluating fluconazole prophylaxis in the SICU. Future trials should focus on more precisely identifying patients at high risk for fungal infections and on determining if broader use of fluconazole alters the distribution of candidal species seen in the SICU and impacts measures of resource utilization such as length of stay and duration of mechanical ventilation.

Antifungal Agents↗
PubMed2005

Transfusion practice and nosocomial infection: assessing the evidence.

PURPOSE OF REVIEW: To evaluate recent literature describing the potential relation between transfusion practice in the intensive care unit and the subsequent risk for nosocomial infection. RECENT FINDINGS: Multiple studies have documented that patients in the intensive care unit often receive transfusions of packed red blood cells while in the intensive care unit. Although the safety of the blood supply has increased substantially over the last decade, nosocomial infection is emerging as an unappreciated potential consequence of transfusion. Research now suggests that transfusion alters the host's immune system. Clinically, this may lead to relative immunosuppression and result in nosocomial infection. Supporting this hypothesis, an association between infection and transfusion has been shown in various settings and for several different types of infections. In both postoperative and medical intensive care unit subjects, administration of packed red blood cell consistently raises the risk for infection. Similarly, transfusion rates correlate with two major nosocomial complications in the intensive care unit: pneumonia and bloodstream infection. Proof of causation remains elusive because of study design issues. Nonetheless, the weight of the evidence favors adding nosocomial infection to the list of potential risks related to packed red blood cell transfusion. SUMMARY: Packed red blood cell transfusion may substantially increase the risk for nosocomial infection. The likely link between transfusion practice and nosocomial infection should factor into the provider's decision when determining when to transfuse.

Bacteremia↗
PubMed2005

Should we use etomidate as an induction agent for endotracheal intubation in patients with septic shock?: a critical appraisal.

Etomidate is commonly used for the facilitation of endotracheal intubation. While etomidate possesses multiple qualities that are beneficial in hemodynamically unstable patients who require a sedative or amnestic, its potential to negatively impact corticosteroid production is well-documented. Given the frequency of relative adrenal insufficiency observed in the critically ill and the increasing use of corticosteroids in patients with septic shock, an appraisal of the status of etomidate as an induction agent in patients with evolving or established septic shock is indicated. A review of the relevant literature suggests that its use in this setting may be harmful. It is proposed that, pending the performance of a randomized, controlled clinical trial, considerable caution should accompany its administration in patients with evolving or established septic shock. The potential role for concomitant empiric steroid replacement and the comparability of alternative induction regimens are also discussed.

Adrenal Glands↗
PubMed2005

Transfusion practice and blood stream infections in critically ill patients.

STUDY OBJECTIVE: To examine the relationship between packed RBC (pRBC) transfusion and the development of ICU-acquired bloodstream infections (BSIs) DESIGN: Secondary analysis of a large, prospective, observational study of transfusion practice in critically ill patients. SETTING: A total of 284 adult ICUs in the United States. PATIENTS: Critically ill adults who lacked BSIs both at ICU admission and 48 h after ICU admission. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: BSIs were prospectively tracked in this study, and diagnosis of a new BSI represented the primary end point. Transfusions administered in the ICU prior to development of a BSI were also prospectively recorded. Of 4,892 patients enrolled in this investigation, 3,502 patients lacked BSIs both at ICU admission and 48 h later. Among these individuals, 117 patients (3.3%) had an ICU-acquired BSI. In multivariate analysis adjusting for severity of illness, primary diagnosis, use of mechanical ventilation, placement of central venous catheters, and ICU length of stay, three variables were independently associated with diagnosis of a new BSI: baseline treatment with cephalosporins (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.26 to 2.68), higher sequential organ failure assessment score measured on ICU days 3 to 4 (OR, 1.11; 95% CI, 1.06 to 1.16), and pRBC transfusion (OR, 2.23; 95% CI, 1.43 to 3.52). The relationship between pRBC transfusion and BSI was evident with both small transfusion volumes (OR with 1- to 2-U pRBC transfusion, 1.89; 95% CI, 1.10 to 3.23) and larger transfusion volumes (OR with > 4-U pRBC transfusion, 2.63; 95% CI, 1.52 to 4.53). CONCLUSIONS: pRBC transfusion is associated with subsequent ICU-acquired BSI. Avoiding unnecessary transfusions may decrease the incidence of BSIs.

Aged↗
PubMed2004

Meta-analysis: outcomes in patients with suspected pulmonary embolism managed with computed tomographic pulmonary angiography.

BACKGROUND: Spiral computed tomographic pulmonary angiography (CTPA) is increasingly being used in the evaluation of patients with clinically suspected pulmonary embolism (PE). However, CTPA as a definitive diagnostic test may be limited by inadequate sensitivity, especially in instances of isolated subsegmental emboli. PURPOSE: To assess the safety of withholding anticoagulation in patients with suspected PE and negative results on CTPA. DATA SOURCES: All relevant studies identified in MEDLINE (1966 to March 2004) and EMBASE (1974 to 2004) and in bibliographies of key articles. The search was not limited to the English language. STUDY SELECTION: The authors selected all published studies that used CTPA to evaluate suspected PE and reported at least 3 months of follow-up in patients not receiving anticoagulation on the basis of a negative CTPA result. DATA EXTRACTION: Two reviewers independently rated study quality on the basis of predetermined criteria. Data were extracted on participants, CTPA technique, diagnostic studies performed, prevalence of PE, number of patients with negative or indeterminate CTPA results who were followed, and subsequent rates of venous thromboembolism and fatal PE. DATA SYNTHESIS: Twenty-three studies reported on 4657 patients with negative CTPA results who did not receive anticoagulation. The 3-month rate of subsequent venous thromboembolic events was 1.4% (95% CI, 1.1% to 1.8%), and the 3-month rate of fatal PE was 0.51% (CI, 0.33% to 0.76%). LIMITATIONS: The CTPA technology used varied across studies and was not applied uniformly in the same step of diagnostic algorithms. Only 1 study used CTPA as the sole diagnostic test. CONCLUSION: The rate of subsequent venous thromboembolism after negative results on CTPA is similar to that seen after negative results on conventional pulmonary angiography. It appears to be safe to withhold anticoagulation after negative CTPA results.

Angiography↗