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Biomedical subjects

Andrew F Shorr

Publications and source records attributed to Andrew F Shorr.

At least 37 records · Page 2Linked to original sources
PubMed2005

Application of a population-based severity scoring system to individual patients results in frequent misclassification.

INTRODUCTION: APACHE II (AP2) was developed to allow a systematic examination of intensive care unit outcomes in a risk adjusted manner. AP2 has been widely adopted in clinical trials to assure broad consistency amongst different groups. Although errors in calculating the true AP2 score may not be reducible below 15%, the self-canceling effect of random errors reduces the importance of such errors when applied to large populations. It has been suggested that a threshold AP2 score be used in clinical decision making for individual patients. This study reports the AP2 scoring errors of researchers involved in a large sepsis trial and models the consequences of such an error rate for individual severe sepsis patients. METHODS: Fifty-six researchers with explicit training in data abstraction and completion of the AP2 score received scenarios consisting of composites of real patient histories. Descriptive statistics were calculated for each scenario. The standard deviations were calculated compared with an adjudicated score. Intraclass correlations for inter-observer reliability were performed using Shrout-Fleiss methodology. Theoretical distribution curves were calculated for a broad range of AP2 scores using standard deviations of 6, 9 and 12. For each curve, the misclassification rate was determined using an AP2 score cut-off of >or=25. The percentage of misclassifications for each true AP2 score was then applied to the corresponding AP2 score obtained from the PROGRESS severe sepsis registry. RESULTS: The error rate for the total AP2 score was 86% (individual variables were in the range 10% to 87%). Intraclass correlation for the inter-observer reliability was 0.51. Of the patients from the PROGRESS registry. 50% had AP2 scores in the range 17 to 28. Within this interquartile range, 70% to 85% of all misclassified patients would reside. CONCLUSION: It is more likely that an individual patient will be scored incorrectly than correctly. The data obtained from the scenarios indicated that as the true AP2 score approached an arbitrary cut-off point of 25, the observed misclassification rate increased. Integrating our study of AP2 score errors with the published literature leads us to conclude that the AP2 is an inappropriate sole tool for resource allocation decisions for individual patients.

APACHE↗
PubMed2005

Discordance between general and pulmonary pathologists in the diagnosis of interstitial lung disease.

BACKGROUND: Interstitial lung diseases (ILDs) often present diagnostic challenges to both the clinician and pathologist. Surgical lung biopsy (SLB) is often pursued in the evaluation of ILD and the clinician uses the histopathologic conclusions to guide management. However, the agreement between general and pulmonary pathologists in histopathologic diagnosis of ILD has not been established. OBJECTIVE: To determine the agreement between general and pulmonary pathologists in the histopathologic interpretation of ILDs and whether disagreements result in changes in clinical management. METHODS: We retrospectively reviewed all patients who underwent SLB for ILD at our institution, between 1996 and 2002. We compared the interpretations of general pathologists to those of pulmonary pathologists to evaluate the degree of inter-rater agreement. We assumed the specialist pathologist represented the "gold standard." We further determined if changes in the histopathologic diagnosis altered clinical management. RESULTS: Of 83 subjects who underwent SLB, 44 (mean age 58.5 +/- 14.2, 47.7% male) were examined by both general and specialty pathologists. There was poor agreement between the two sets of reviewers. The histopathologic interpretation by the specialist pathologist differed from the generalist in 52.3% of cases (kappa 0.21, P < 0.0001). This high rate of discordance led to frequent (60.0%) changes in clinical management. As a screening test for usual interstitial pneumonia, the observations of the general pathologist had moderate sensitivity and specificity (76.5% and 66.7%, respectively). CONCLUSIONS: General and pulmonary pathologists often differ in their interpretation of the histopathology in ILD. This significant discordance may have important clinical implications for patient care.

Adult↗
PubMed2005

Quinolones for treatment of nosocomial pneumonia: a meta-analysis.

Although quinolones are often used to treat nosocomial pneumonia (NP), there have been few trials documenting their efficacy in treating NP. Given the growing use of quinolones and issues regarding resistance, we conducted a meta-analysis of all trials of quinolones for treatment of NP. We identified 5 randomized trials comparing quinolones with other agents used to treat NP. The studies varied in both quality and sample size and included a total of nearly 1200 subjects. Four of the 5 trials used ciprofloxacin, administered every 8 h, whereas the fifth used levofloxacin administered daily. In 3 trials, the comparator agent was imipenem-cilistatin, whereas, in 2 trials, ceftazadime was the comparator agent. The efficacy of quinolones and comparator antibiotics was similar, with a pooled odds ratio for clinical cure of 1.12 (95% confidence interval, 0.80-1.55). Neither microbiological eradication rates nor mortality rates varied on the basis of antimicrobial selection.

Anti-Infective Agents↗
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

Preventing pneumonia: the role for pneumococcal and influenza vaccines.

Streptococcus pneumoniae and influenza cause a wide spectrum of illness and result in substantial morbidity and mortality. They are significant public health concerns, and vaccines against both organisms exist. The pneumococcal polysaccharide vaccine has been available in its current form for over 20 years. Nonetheless, definitive evidence from prospective trials of its efficacy is lacking. Experts recommend that patients at high risk for pneumococcal infection and complications from this process be vaccinated. The role for revaccination remains controversial. Traditional influenza vaccine is composed of three virus types and decreases rates of serologically confirmed cases of influenza, hospital admissions for respiratory infection, and mortality. The pneumococcal and influenza vaccines are considered cost-effective options for pneumonia prevention.

Adult↗
PubMed2005

Intralobular bronchopulmonary sequestrations associated with bronchogenic cysts.

We present three cases of intralobar bronchopulmonary sequestrations with associated congenital bronchogenic cysts. As congenital abnormalities tend to be found together, these cases question the notion that intralobar sequestrations only occur secondary to chronic inflammation or infection, and suggest they can be congenital lesions.

Adult↗
PubMed2005

A multicenter, randomized, double-blind, retrospective comparison of 5- and 10-day regimens of levofloxacin in a subgroup of patients aged > or =65 years with community-acquired pneumonia.

OBJECTIVE: This subgroup analysis sought to determine the efficacy and tolerability of a 5-day regimen of levofloxacin 750 mg/d compared with a 10-day regimen of levofloxacin 500 mg/d in the treatment of community-acquired pneumonia (CAP) in elderly patients (aged > or =65 years). METHODS: This subgroup analysis was based on the outcomes in patients aged > or =65 years from a randomized, double-blind, controlled trial conducted at 70 US centers. Patients in Pneumonia Severity Index (PSI) class I/II and III/IV were randomized to receive levofloxacin 750 mg/d for 5 days or levofloxacin 500 mg/d for 10 days. Study investigators assessed clinical and microbiologic outcomes 7 to 14 days after administration of the last dose of medication and collected adverse events for 30 days after the last dose. RESULTS: This analysis included 177 elderly patients, 80 receiving levofloxacin 750 mg/d for 5 days and 97 receiving levofloxacin 500 mg/d for 10 days. Although most demographic and baseline clinical characteristics were comparable between the 2 groups, the group that received levofloxacin 500 mg/d was older than the group that received levofloxacin 750 mg/d (median age, 76.0 vs 72.5 years, respectively; P = 0.029) and had a higher mean PSI score (90.7 vs 83.1; P = 0.017). Despite the halved duration of therapy, unadjusted clinical success rates were comparable between the 2 groups (89.0% and 91.9% in the 750- and 500-mg arms, respectively; 95% CI, -7.1 to 12.7). Microbiologic eradication rates were 90.3% (28/31) in the 750-mg arm and 87.5% (14/16) in the 500-mg arm (P = NS). Multivariate analysis adjusting for baseline PSI score indicated that treatment assignment was not statistically associated with clinical success (adjusted odds ratio for clinical success with 500-mg dose, 1.92; 95% CI, 0.62 to 5.99). The incidence of treatment-emergent adverse events did not differ between the 2 study treatments. The most common adverse events in both groups were insomnia, constipation, and headache. CONCLUSIONS: This subgroup analysis found that levofloxacin 750 mg/d for 5 days was well tolerated in the treatment of CAP in elderly patients. Undajusted and adjusted rates of clinical success were statistically similar between levofloxacin 750 mg/d for 5 days and levofloxacin 500 mg/d for 10 days.

Aged↗
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

Dynamic evolution of coagulopathy in the first day of severe sepsis: relationship with mortality and organ failure.

OBJECTIVE: To determine whether changes in coagulation biomarkers during the first day of severe sepsis correlate with progression from single to multiple organ failure and subsequent death. DESIGN: Analysis of secondary endpoints in a prospective, randomized, placebo-controlled, multinational clinical trial (PROWESS). SETTING: The study involved 164 medical centers. PATIENTS: A total of 840 patients who met criteria for severe sepsis and were randomized to receive placebo plus supportive care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Coagulation biomarkers, prothrombin time, antithrombin activity, and D-dimer and protein C levels were measured, and Sequential Organ Failure Assessment was performed daily. Multiple logistic regression analysis identified baseline antithrombin activity <54% and changes in prothrombin time, D-dimer, and antithrombin activity during the first calendar day after the onset of the first sepsis-induced organ dysfunction (i.e., the first day of severe sepsis, day 1) as predictive of 28-day mortality (p < or = .01). A composite coagulopathy score was determined using points for predetermined levels of change from baseline to day 1. The composite coagulopathy score correlated with progression from single to multiple organ failure (p = .0007), time to resolution of organ failure (p = .0004), and 28-day mortality (p < .0001). Combining the composite coagulopathy score with the Acute Physiology and Chronic Health Evaluation (APACHE) II score improved ability to identify patients who would progress to multiple organ failure (area under receiver operating characteristic curve 0.61 APACHE II vs. 0.65 APACHE II + composite coagulopathy score) and who would die (area under receiver operating characteristic curve 0.69 APACHE II vs. 0.74 APACHE II + composite coagulopathy score). CONCLUSIONS: Continuation or worsening of coagulopathy during the first day of severe sepsis was associated with increased development of new organ failure and 28-day mortality. These results further suggest that coagulation abnormalities contribute to organ failure and death.

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

Ineffectiveness of routine abdominal radiography in patients with gastrointestinal hemorrhage admitted to an intensive care unit.

GOALS: To determine the utility of plain abdominal radiography in the initial evaluation of acute gastrointestinal (GI) hemorrhage in a medical intensive care unit. BACKGROUND: Plain abdominal radiographs are frequently used in the routine evaluation of patients with GI bleeding. The utility of these studies in the intensive care unit setting is unclear. STUDY: The study was a retrospective chart review of 71 adult subjects admitted to a medical intensive care unit with the diagnosis of GI bleeding. Subjects were excluded if they presented with peritoneal signs, received an abdominal CT scan in the 24 hours prior to admission, or were chronically treated with immunosuppressive medication. Subjects were divided into two cohorts based on whether or not they underwent plain abdominal radiography during the first hospital day. The primary study endpoints were hospital mortality, intensive care unit length of stay, and whether or not radiographic findings altered clinical management. RESULTS: Of the 71 patients admitted with a diagnosis of GI bleeding (mean age 65.8 +/- 14.5 years, 73.2% male), 56 (79%) had a plain abdominal radiograph performed. Subjects who had a plain film did not differ significantly from those who did not in age, gender, degree of anemia, degree of coagulopathy, or in severity of illness as measured by Acute Physiology and Chronic Health Evaluation (APACHE II) score. There was no statistically significant difference in hospital mortality or intensive care unit length of stay between patients who received plain films and those who did not. In no subject (0%; 95% confidence interval, 0%-5.4%) did abdominal radiography reveal an abnormality that altered clinical management. CONCLUSIONS: Based on our observations, plain films of the abdomen do not appear to alter clinical outcomes or management decisions for patients with GI bleeding and normal abdominal examinations who are admitted to the intensive care unit.

Aged↗
PubMed2005

Outcomes and safety of surgical lung biopsy for interstitial lung disease.

STUDY OBJECTIVES: To determine the safety of surgical lung biopsy (SLB) in patients with interstitial lung disease (ILD), and specifically in those with idiopathic pulmonary fibrosis (IPF). DESIGN: Retrospective cohort. SETTING: Tertiary care university-affiliated military medical center. PATIENTS: Individuals undergoing SLB for suspected ILD. MEASUREMENTS AND RESULTS: We examined outcomes for subjects with a clinical diagnosis of ILD who had been designated to undergo SLB. Mortality (assessed at 30 and 90 days) following SLB represented the primary end point. Morbidity resulting from complications from SLB served as a secondary end point. The cohort included 83 patients (mean [+/- SD] age, 57.3 +/- 14.2 years; men, 57.8%). IPF was eventually diagnosed in slightly more than half of the subjects. Overall, 30-day and 90-day mortality rates were low (4.8% and 6.0%, respectively). Subjects with IPF did well with SLB (30-day mortality rate, 7.1%) and did not face a higher risk of either death or complications relative to individuals with non-IPF forms of ILD. The only predictors of perioperative mortality were either the need for mechanical ventilation (MV) at the time of SLB or being immunosuppressed prior to undergoing SLB. Excluding persons who met either criterion yielded an overall 90-day post-SLB mortality rate of 1.5% in persons with IPF. Approximately 40% of patients in whom IPF was eventually diagnosed were initially thought to have another form of ILD. CONCLUSIONS: Persons with IPF tolerate SLB well. Requiring MV or being immunosuppressed is associated with an increased risk for death following SLB. Safety concerns should not preclude referral for SLB in patients who are clinically suspected of having IPF.

Adult↗
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↗
PubMed2005

Ventilator-associated pneumonia: insights from recent clinical trials.

Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in the ICU and contributes disproportionately to both poor outcomes and the high cost of care in critically ill patients. While VAP has been the focus of extensive research, little consensus exists about methods for diagnosis, treatment, or prevention. Delays in initiating appropriate therapy, antibiotic resistance due to indiscriminate and prolonged use of broad-spectrum antibiotics, and treatment of patients with a low risk of VAP (based on clinical pulmonary infection scores) represent a sample of VAP-related issues that have been addressed in recent clinical trials. Educational programs for VAP prevention and other nonpharmacologic strategies aimed at eliminating VAP have also been explored in clinical investigations. This review highlights selected areas of new clinical research on VAP treatment and prevention in order to place their significance in context.

Anti-Bacterial Agents↗