Responding to a small-scale bioterrorist anthrax attack: cost-effectiveness analysis comparing preattack vaccination with postattack antibiotic treatment and vaccination.

BACKGROUND: In 2001, a small-scale bioterrorism-related anthrax attack was perpetrated via the US mail. The optimal future response may require strategies different from those required in a large-scale attack. METHODS: We conducted a cost-effectiveness analysis using Monte Carlo simulation during a 10-year time frame from a societal perspective to determine the optimal response strategy for a small-scale anthrax attack perpetrated against US Postal Service distribution centers in a large metropolitan area. Three strategies were compared: preattack vaccination of all US distribution center postal workers, postattack antibiotic therapy followed by vaccination of exposed personnel, and postattack antibiotic therapy without vaccination of exposed personnel. Outcome measures were costs, quality-adjusted life-years, and incremental cost-effectiveness. The probabilities for anthrax exposure and infection; vaccine and antibiotic benefits, risks, and costs; and associated clinical outcomes were derived from the medical literature and from bioterrorism experts. RESULTS: Postattack antibiotic therapy and vaccination of exposed postal workers is the most cost-effective response compared with other strategies. The incremental cost-effectiveness is $59 558 per quality-adjusted life-year compared with postattack antibiotic therapy alone. Preattack vaccination of all distribution center workers is less effective and more costly than the other 2 strategies. Assuming complete adherence to preattack vaccination, the incremental cost-effectiveness compared with postattack antibiotic therapy alone is almost $2.6 million per quality-adjusted life-year. CONCLUSION: Despite uncertainties about a future anthrax attack and exposure risk, postattack antibiotic therapy and vaccination of exposed personnel seems to be the optimal response to an attack perpetrated through the US Postal Service.

Using patient traffic control to reduce treatment delays for high-risk patients at a VA hospital.

BACKGROUND: For patients at high risk of function-limiting or life-limiting disease, the time elapsed between first clinical presentation, diagnosis, and treatment can influence the likelihood of treatment success. METHODS: A systematic change in the management of high-risk patients was undertaken. This approach includes identifying primary provider responsibility, establishing communication expectations between providers, developing a tracking system to actively monitor patients (patient traffic control), and using a time guideline to assess patient progression. A 60-day time frame was established for the time from first clinical presentation to diagnostic exclusion or treatment initiation. RESULTS: In a one-year period, 288 high-risk patients were entered into patient traffic control, 211 (73%) of whom were monitored in the primary care setting. The median time to diagnostic exclusion or treatment was 43 days (mean, 58.5 days). Sixty-six percent of all patients achieved diagnostic exclusion or treatment by 60 days. Of the 95 patients monitored for > 60 days, 56% had delays caused by patient noncompliance or because of the appropriate need for long-term serial radiographic monitoring. Thirty-eight patients (13.1%) demonstrated problems with appointment nonadherence. None were lost to follow-up. DISCUSSION: The patient traffic control approach enabled the management of the majority of high-risk patients within 60 days of presentation.

Discriminating inhalational anthrax from community-acquired pneumonia using chest radiograph findings and a clinical algorithm.

BACKGROUND: Limiting the effects of a large-scale bioterrorist anthrax attack will require rapid and accurate detection of the earliest victims. We undertook this study to improve physicians' ability to rapidly detect inhalational anthrax victims. METHODS: We conducted a case-control study to compare chest radiograph findings from 47 patients from historical inhalational anthrax cases and 188 community-acquired pneumonia control subjects. We then used classification tree analyses to derive an algorithm of chest radiograph findings and clinical characteristics that accurately and explicitly discriminated between inhalational anthrax and community-acquired pneumonia. RESULTS: Twenty-two of the 47 patients from historical inhalational anthrax cases (46.8%) had reported chest radiograph findings. All 22 case patients (100%) had mediastinal widening, pleural effusion, or both. However, 16 case patients (72.7%) also had infiltrates. In comparison, all 188 community-acquired control subjects had reported chest radiographs. Of these, 127 control subjects (67.6%) had infiltrates, 43 control subjects (22.9%) had pleural effusions, and 15 control subjects (8.0%) had mediastinal widening. A derived algorithm with three predictor variables (chest radiograph finding of mediastinal widening, altered mental status, and elevated hematocrit) is 100% sensitive (95% confidence interval [CI], 73.5 to 100) and 98.3% specific (95% CI, 95.1 to 99.6). The derivation process used 12 patients with inhalational anthrax and 177 control subjects with community-acquired pneumonia who had information available for all three variables. CONCLUSIONS: There are significant chest radiograph differences between inhalational anthrax and community-acquired pneumonia, but none of the chest radiograph findings are both highly sensitive and highly specific. The derived clinical algorithm can improve physicians' ability to discriminate inhalational anthrax from community-acquired pneumonia, but its utility is limited to previously healthy individuals and its accuracy may be limited by missing values.

Process evaluation in an intervention designed to improve rates of colorectal cancer screening in a VA medical center.

Colorectal cancer (CRC) is the third most common cancer in the United States. Although CRC screening is recommended for individuals 50 years and older, screening completion rates are low. This can be attributed to provider and patient barriers. We developed an intervention to improve provider recommendation and patient screening among noncompliant male veterans in a 2-year randomized controlled trial and examined the relationship between participation and study outcomes among patients and providers. Overall, providers who attended intervention sessions recommended CRC screening during 64% of patient visits and providers who did not attend any intervention sessions recommended screening during 54% of visits (p < .01). Patients of providers who attended intervention sessions also were more likely to be screened (42% versus 29%, p < .05). The patient intervention did not have the desired impact. The subgroup of patients in the patient intervention was not more likely to complete CRC screening.

Health care provider-directed intervention to increase colorectal cancer screening among veterans: results of a randomized controlled trial.

PURPOSE: Colorectal cancer screening is the most underused cancer screening tool in the United States. The purpose of this study was to test whether a health care provider-directed intervention increased colorectal cancer screening rates. PATIENTS AND METHODS: The study was a randomized controlled trial conducted at two clinic firms at a Veterans Affairs Medical Center. The records of 5,711 patients were reviewed; 1,978 patients were eligible. Eligible patients were men aged 50 years and older who had no personal or family history of colorectal cancer or polyps, had not received colorectal cancer screening, and had at least one visit to the clinic during the study period. Health care providers in the intervention firm attended a workshop on colorectal cancer screening. Every 4 to 6 months, they attended quality improvement workshops where they received group screening rates, individualized confidential feedback, and training on improving communication with patients with limited literacy skills. Medical records were reviewed for colorectal cancer screening recommendations and completion. Literacy level was assessed in a subset of patients. RESULTS: Colorectal cancer screening was recommended for 76.0% of patients in the intervention firm and for 69.4% of controls (P = .02). Screening tests were completed by 41.3% of patients in the intervention group versus 32.4% of controls (P = .003). Among patients with health literacy skills less than ninth grade, screening was completed by 55.7% of patients in the intervention group versus 30% of controls (P < .01). CONCLUSION: A provider-directed intervention with feedback on individual and firm-specific screening rates significantly increased both recommendations and colorectal cancer screening completion rates among veterans.

Screening primary care patients for hereditary hemochromatosis with transferrin saturation and serum ferritin level: systematic review for the American College of Physicians.

BACKGROUND: Therapeutic phlebotomy for hereditary hemochromatosis is relatively safe and presumably efficacious when offered before cirrhosis develops, so screening primary care patients is of substantial interest. PURPOSE: To conduct a systematic review of the evidence on 1) the prevalence of the disease in primary care, 2) the risk for morbid or fatal complications for untreated patients, 3) the diagnostic usefulness of transferrin saturation and serum ferritin level in identifying early disease, 4) the efficacy of early treatment, and 5) whether the benefits of screening outweigh the risks. DATA SOURCES: MEDLINE search from 1966 through April 2004, complemented by reference review of identified original studies and review articles published in English. STUDY SELECTION: PubMed Clinical Queries filters search of prognosis, diagnosis, etiology, or treatment were used depending on the question. Two authors reviewed all titles and abstracts. DATA EXTRACTION: Two investigators independently reviewed extracted data. DATA SYNTHESIS: The prevalence of hereditary hemochromatosis was 1 in 169 patients to 1 in 556 patients (n = 3 studies). Uncontrolled, prospective studies of genetic homozygous patients did not consistently identify a link to overt hereditary hemochromatosis. A serum ferritin level less than 1000 microg/L was predictive of absence of cirrhosis. Six studies demonstrated reduced survival in patients with cirrhosis. Diagnostic studies varied with respect to case definition. No blinded, independent comparisons of screening tests with the gold standard (biopsy or results of quantitative phlebotomy) or randomized, controlled trials of phlebotomy were identified. Cost-effectiveness analysis was limited by lack of prospective data on the natural history of the disease. LIMITATIONS: Varied case definition and lack of prospective cohort studies or randomized trials. CONCLUSIONS: The available evidence does not demonstrate that benefits outweigh the risks and costs of screening for hemochromatosis.

Colorectal cancer screening knowledge, attitudes, and beliefs among veterans: does literacy make a difference?

PURPOSE: To evaluate whether lower literacy is associated with poorer knowledge and more negative attitudes and beliefs toward colorectal cancer screening among veterans without recent colorectal cancer screening. PATIENTS AND METHODS: Three hundred seventy-seven male veterans, age 50 years and older, who had not undergone recent colorectal cancer screening, were surveyed about their knowledge, attitudes, and beliefs regarding colorectal cancer screening. Patients' literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine, an individually administered screening test for reading. RESULTS: Thirty-six percent of the 377 men had an eighth grade literacy level or higher. Men with lower literacy were 3.5 times as likely not to have heard about colorectal cancer (8.8% v 2.5%; P =.006), 1.5 times as likely not to know about screening tests (58.4% v 40.9%; P =.0001), and were more likely to have negative attitudes about fecal occult blood testing (FOBT), but not about flexible sigmoidoscopy. Specifically, men with lower literacy skills were two times as likely to be worried that FOBT was messy (26.7% v 13.3%; P =.008), 1.5 times as likely to feel that FOBT was inconvenient (28.7% v 18%; P =.05), and four times as likely to state they would not use an FOBT kit even if their physician recommended it (17.9% v 4.0%; P =.02). CONCLUSION: Limited literacy may be an overlooked barrier in colorectal cancer screening among veterans.

Colorectal cancer screening among African-American and white male veterans.

BACKGROUND: Population-based studies from Medicare and privately insured individuals have consistently identified lower rates of colorectal cancer-screening tests among African-American versus white individuals. The purpose of this study was to evaluate whether, at a Veterans Affairs (VA) medical center, similar racial/ethnic differences in colorectal cancer screening could be identified. METHODS: Study participants were male veterans, aged > or =50, attending a general medicine clinic in a VA hospital, who had not had either a fecal occult blood test (FOBT) within the past year or a flexible sigmoidoscopy/colonoscopy within the past 5 years. Based on review of electronic medical records, rates of physician recommendation for FOBT, flexible sigmoidoscopy, or colonoscopy, and patient completion of these tests were obtained and compared by race/ethnicity. RESULTS: Sixty percent of 1599 veterans had not undergone recent colorectal cancer screening. Physicians recommended colorectal screening tests equally among African-American and white patients (71.0% vs 68.2%, p=0.44). African-American patients were 1.3 times more likely than white patients to receive colorectal screening procedures (36.3% vs 28.9%, p=0.03). CONCLUSIONS: In contrast to other settings, in a general medicine clinic at a VA hospital, rates of colorectal cancer-screening tests were not lower for African-American patients compared to white patients.

Taking a patient safety approach to an integration of two hospitals.

BACKGROUND: Consolidation of inpatient care between two acute care medical centers brings many challenges, including an increased risk of an untoward event during patient transfer and impaired hospital performance during the postintegration period. When the Jesse Brown Department of Veterans Affairs (VA) Medical Center in Chicago integrated two acute medical-surgical inpatient facilities, the challenges intrinsic to simultaneously integrating acute medical-surgical programs and academic training programs necessitated a novel approach. STRATEGIES USED: Several patient safety-related tools were used for the safe transfer of patients and for sustaining hospital performance after integration. These tools included Failure Mode and Effects Analysis (FMEA) of the move process, process action teams to bridge the differences in standard nursing unit operation, and an integration score card to monitor and evaluate the impact of the integration on organization performance. RESULTS: Patient care was not disrupted except for a transient reduction in elective surgical procedures during the week before the move. Postintegration data indicated reduced operating room cancellations, sustained inpatient capacity and access, and comparable findings in patient falls and methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci infections. CONCLUSION: The impact of several patient safety tools and interventions was reflected in the fact that performance remained constant or improved for the predefined measures of access and quality.

Clopidogrel-associated TTP: an update of pharmacovigilance efforts conducted by independent researchers, pharmaceutical suppliers, and the Food and Drug Administration.

BACKGROUND AND PURPOSE: Since the 1999 identification of clopidogrel-associated thrombotic thrombocytopenic purpura (TTP) through independent active surveillance, subsequent cases have been identified by pharmaceutical suppliers of clopidogrel and the Food and Drug Administration (FDA). For cases of clopidogrel-associated TTP reported between 1998 to 2002, we evaluated the quality and timeliness of data from 3 reporting systems-independent active surveillance (n=13), pharmaceutical suppliers (n=24), and the FDA (n=13)-and identified prognostic factors associated with mortality. METHODS: This study assessed the completeness of information on TTP diagnosis, treatment response, and causality from the 3 reporting systems. In addition, predictors of mortality were identified through classification tree analysis. RESULTS: Completeness, timeliness, and certainty of diagnosis were best for cases obtained by active surveillance, intermediate for cases reported to the pharmaceutical supplier, and poorest for cases reported directly to the FDA. Clopidogrel had been used for

Prognostic judgments and triage decisions for patients with acute congestive heart failure.

STUDY OBJECTIVES: To determine how well triage physicians judge the probability of death or severe complications that require treatment only available in an ICU to maintain life for patients with acute congestive heart failure (CHF). DESIGN: Prospective cohort study. SETTING: An urban university hospital, a Veteran's Administration hospital, and a community hospital. PATIENTS OR PARTICIPANTS: Patients were those visiting the emergency department (ED) with acute CHF, excluding those who already required a treatment only available in an ICU to maintain life, and those with possible or definite myocardial infarction. Physician participants were those caring for the patients in the ED. MEASUREMENTS AND RESULTS: We performed chart reviews to ascertain whether each patient died or had severe complications develop by 4 days. We collected judgments of the probability of this outcome from the physicians taking care of the study patients in the ED. The prevalence of death or severe complications was 43 per 1,032 patients (4.2%). The mean +/- SD of physicians' judgments of the probability of this outcome was 32.1 +/- 28.4%. A calibration curve that stratified these judgments by decile demonstrated that physicians consistently overestimated this probability (p < 0.01). Physicians' judgments were only moderately good at discriminating which patients would have the outcome (receiver operating characteristic curve area, 0.715). Patients admitted to an ICU received the highest average predicted probability (56.4%), followed by those admitted to a telemetry unit (34.1%), to a regular hospital ward (29.8%), and those sent home (17.9%.) CONCLUSIONS: Physicians drastically overestimated the probability of a severe complication that would require critical care for patients with acute CHF who were candidates for ICU admission. Their judgments of this probability were associated with their triage decisions, as they should be according to several guidelines for ICU triage. Overestimation of the probability of severe complications may have lead to overutilization of scarce critical care resources. Current critical care triage guidelines should be revised to take this difficulty into account, and better predictive models for patients potentially requiring critical care should be developed.

Cost-effectiveness comparison of response strategies to a large-scale anthrax attack on the chicago metropolitan area: impact of timing and surge capacity.

Rapid public health response to a large-scale anthrax attack would reduce overall morbidity and mortality. However, there is uncertainty about the optimal cost-effective response strategy based on timing of intervention, public health resources, and critical care facilities. We conducted a decision analytic study to compare response strategies to a theoretical large-scale anthrax attack on the Chicago metropolitan area beginning either Day 2 or Day 5 after the attack. These strategies correspond to the policy options set forth by the Anthrax Modeling Working Group for population-wide responses to a large-scale anthrax attack: (1) postattack antibiotic prophylaxis, (2) postattack antibiotic prophylaxis and vaccination, (3) preattack vaccination with postattack antibiotic prophylaxis, and (4) preattack vaccination with postattack antibiotic prophylaxis and vaccination. Outcomes were measured in costs, lives saved, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We estimated that postattack antibiotic prophylaxis of all 1,390,000 anthrax-exposed people beginning on Day 2 after attack would result in 205,835 infected victims, 35,049 fulminant victims, and 28,612 deaths. Only 6,437 (18.5%) of the fulminant victims could be saved with the existing critical care facilities in the Chicago metropolitan area. Mortality would increase to 69,136 if the response strategy began on Day 5. Including postattack vaccination with antibiotic prophylaxis of all exposed people reduces mortality and is cost-effective for both Day 2 (ICER=$182/QALY) and Day 5 (ICER=$1,088/QALY) response strategies. Increasing ICU bed availability significantly reduces mortality for all response strategies. We conclude that postattack antibiotic prophylaxis and vaccination of all exposed people is the optimal cost-effective response strategy for a large-scale anthrax attack. Our findings support the US government's plan to provide antibiotic prophylaxis and vaccination for all exposed people within 48 hours of the recognition of a large-scale anthrax attack. Future policies should consider expanding critical care capacity to allow for the rescue of more victims.

Derivation of a triage algorithm for chest radiography of community-acquired pneumonia patients in the emergency department.

BACKGROUND: Community-acquired pneumonia (CAP) accounts for 1.5 million emergency department (ED) patient visits in the United States each year. OBJECTIVES: To derive an algorithm for the ED triage setting that facilitates rapid and accurate ordering of chest radiography (CXR) for CAP. METHODS: The authors conducted an ED-based retrospective matched case-control study using 100 radiographic confirmed CAP cases and 100 radiographic confirmed influenzalike illness (ILI) controls. Sensitivities and specificities of characteristics assessed in the triage setting were measured to discriminate CAP from ILI. The authors then used classification tree analysis to derive an algorithm that maximizes sensitivity and specificity for detecting patients with CAP in the ED triage setting. RESULTS: Temperature greater than 100.4 degrees F (likelihood ratio = 4.39, 95% confidence interval [CI] = 2.04 to 9.45), heart rate greater than 110 beats/minute (likelihood ratio = 3.59, 95% CI = 1.82 to 7.10), and pulse oximetry less than 96% (likelihood ratio = 2.36, 95% CI = 1.32 to 4.20) were the strongest predictors of CAP. However, no single characteristic was adequately sensitive and specific to accurately discriminate CAP from ILI. A three-step algorithm (using optimum cut points for elevated temperature, tachycardia, and hypoxemia on room air pulse oximetry) was derived that is 70.8% sensitive (95% CI = 60.7% to 79.7%) and 79.1% specific (95% CI = 69.3% to 86.9%). CONCLUSIONS: No single characteristic adequately discriminates CAP from ILI, but a derived clinical algorithm may detect most radiographic confirmed CAP patients in the triage setting. Prospective assessment of this algorithm will be needed to determine its effects on the care of ED patients with suspected pneumonia.

Systematic review and meta-analysis of monotherapy compared with combined androgen blockade for patients with advanced prostate carcinoma.

BACKGROUND: The current systematic review and meta-analysis compared monotherapy and combined androgen blockade in the treatment of men with advanced prostate carcinoma. Outcomes of interest included overall, cancer specific, and progression-free survival; time to treatment failure; adverse events; and quality of life. METHODS: The literature search identified randomized trials comparing monotherapy (orchiectomy and luteinizing hormone-releasing hormone [LHRH] agonists) with combination therapy using orchiectomy or a LHRH agonist plus a nonsteroidal or steroidal antiandrogen. Dual independent review occurred. The meta-analysis used a random effects model. RESULTS: Twenty-one trials compared survival after monotherapy with survival after combined androgen blockade (n = 6871 patients). The meta-analysis found no statistically significant difference in survival at 2 years between patients treated with combined androgen blockade and those treated with monotherapy (20 trials; hazard ratio [HR] = 0.970; 95% confidence interval [95% CI], 0.866-1.087). The authors determined a statistically significant difference in survival at 5 years that favored combined androgen blockade (10 trials; HR = 0.871; 95% CI, 0.805-0.942). For the subgroup of patients with a good prognosis, there was no statistically significant difference in survival. Adverse effects leading to withdrawal from therapy occurred more often with combined androgen blockade. To the authors' knowledge there is little evidence published to date comparing the effects of combined androgen blockade and monotherapy on quality of life, but the single randomized trial that adequately addressed this outcome reported an advantage for monotherapy over combined androgen blockade. CONCLUSIONS: A thorough examination of the usefulness of combined androgen blockade must balance the modest increase in expected survival observed at 5 years against the increased risk of adverse effects and the potential for adversely affecting the patient's overall quality of life.