During the 2001 US anthrax attacks, mortality from inhalational anthrax was significantly lower than had been reported historically, which was attributed in part to early identification and timely treatment. During future attacks, clinicians will rely on published descriptions of the clinical features of inhalational anthrax to rapidly diagnose patients and institute appropriate treatment. Published descriptions of typical inhalation anthrax usually include patients presenting with cough, dyspnea, or chest pain and found to have abnormal lung examination results with pleural effusions or enlarged mediastinum.

The purpose of this article is to evaluate whether atypical presentations of inhalational anthrax occur and to describe the features of these presentations. We define atypical presentations as those in patients with confirmed anthrax infection who do not have known cutaneous, gastrointestinal, or inhalational ports of entry. We reviewed the case reports of 42 patients with atypical anthrax (published between 1900 and 2004) that may have had an inhalational source of infection to evaluate whether their clinical presentations differed from the typical findings of inhalational anthrax. Patients with atypical anthrax were less likely to have cough, chest pain, or abnormal lung examination results than patients with typical inhalational anthrax (P.05 for all comparisons). A previously published screening protocol for patients with suspected anthrax correctly identified 91% of patients with atypical presentations.

We conclude that although uncommon, atypical presentations of inhalational anthrax likely occur. Timely diagnosis and treatment of patients with inhalational anthrax require clinical awareness of the full spectrum of signs and symptoms associated with inhalational anthrax.

Background: The reported accuracy of transbronchial needle aspiration (TBNA) for mediastinal staging in non- small cell lung cancer (NSCLC) varies widely. We performed a meta-analysis to estimate the accuracy of TBNA for mediastinal staging in NSCLC.

Methods: We searched Medline, Embase and the bibliographies of retrieved articles, with no language restriction, for studies evaluating TBNA accuracy. We used meta-analytic methods to construct summary receiver- operating characteristic curves and to pool sensitivity and specificity.

Results: Thirteen studies met inclusion criteria, including six studies that surgically confirmed all TBNA results and enrolled at least 10 patients with and without mediastinal metastasis (tier 1). Methodologic quality varied, but did not affect diagnostic accuracy. In tier 1 studies, the median prevalence of mediastinal metastasis was 34%. Using a random effects model, the pooled sensitivity and specificity were 39% (95% CI, 17% to 61%) and 99% (95% CI, 96% to 100%), respectively. Compared with tier 1 studies, median prevalence of mediastinal metastasis (81%; p=0.002) and pooled sensitivity (78%; 95% CI, 71% to 84%; p=0.009) were higher in non-tier 1 studies. Sensitivity analysis confirmed that the sensitivity of TBNA depends critically on the prevalence of mediastinal metastasis. The pooled major complication rate was 0.3% (95%CI, 0.01% to 4%).

Conclusions: When properly performed, TBNA is highly specific for identifying mediastinal metastasis in patients with NSCLC, but sensitivity depends critically on the study methods and patient population. In populations with a lower prevalence of mediastinal metastasis, the sensitivity of TBNA is much lower than reported in recent lung cancer guidelines.

CONTEXT: Little is known about how the pharmaceutical industry responds to evidence of harm associated with its products, such as the publication in July 2002 of the Women's Health Initiative Estrogen Plus Progestin Trial (WHI E+P) report demonstrating that standard-dose Prempro produced significant harm and lacked net benefits.

OBJECTIVE: To examine pharmaceutical industry response to the WHI E+P results by analyzing promotional expenditures for hormone therapy before and after July 2002.

DESIGN AND SETTING: Nationally representative and prospectively collected longitudinal data (January 2001 through December 2003) on prescribing and promotion of hormone therapies were obtained from IMS Health and Consumer Media Reports.

MAIN OUTCOME MEASURES: Trends in quarterly prescriptions for hormone therapy and expenditures on 5 modes of drug promotion: samples, office-based detailing, hospital-based promotion, journal advertisements, and direct-to-consumer advertising.

RESULTS: Prior to the WHI E+P report, prescribing rates and promotional spending for hormone therapy were stable. In the quarter before the WHI E+P report (April-June 2002), 22.4 million prescriptions for hormone therapy were dispensed and $71 million was spent on promotion (in annual terms, $350 per year per US physician). Within 9 months of the report's publication (quarter 1 of 2003), there was a 32% decrease in hormone therapy prescriptions, and a nadir had been reached for promotional spending (37% decrease compared with pre-WHI E+P levels). Spending decreased for all promotional activities and most hormone therapies. Overall, the greatest declines were for samples (36% decrease as of quarter 1 of 2003) and direct-to-consumer advertising (100% decrease). The greatest declines in promotion occurred for standard-dose Prempro (61% decrease as of quarter 1 of 2003), the agent implicated by the WHI E+P report. More recently, promotional efforts have increased, particularly for lower-dose Prempro, a resurgence associated with modestly increased prescriptions for this newer agent.

CONCLUSIONS: Concordant with its widespread use, hormone therapy was among the most heavily promoted medications prior to the WHI E+P report. Following reporting of the evidence of harm from this trial, there was a substantial decline in promotional spending for hormone therapy, particularly for the agents most directly implicated in the trial. Interrelated with the impact of the trial results themselves and the ensuing media coverage, reduced promotion may have contributed to a substantial decline in hormone therapy prescriptions.

PURPOSE: To compare the diagnostic accuracy of computed tomography (CT) and positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) for mediastinal staging in patients with non-small-cell lung cancer and to determine whether test results are conditionally dependent (the sensitivity and specificity of FDG-PET depend on the presence or absence of enlarged mediastinal lymph nodes on CT).

DATA SOURCES: Computerized search of MEDLINE, EMBASE, BIOSIS, and CancerLit through March 2003 and reference lists of retrieved studies and review articles.

STUDY SELECTION: Studies in any language that examined FDG-PET for mediastinal staging in patients with known or suspected non-small-cell lung cancer, enrolled at least 10 participants (including at least 5 participants with mediastinal metastasis), and provided enough data to permit calculation of sensitivity and specificity for identifying lymph node involvement.

DATA EXTRACTION: One reviewer (of non-English-language studies) or 2 reviewers (of English-language studies) independently evaluated studies for inclusion, rated methodologic quality, and abstracted relevant data.

DATA SYNTHESIS: Thirty-nine studies met inclusion criteria. Methodologic quality varied, but few aspects of study quality affected diagnostic accuracy. The authors constructed summary receiver-operating characteristic curves for CT and FDG-PET. Positron emission tomography with 18-fluorodeoxyglucose was more accurate than CT for identifying lymph node involvement (P 0.001). For CT, median sensitivity and specificity were 61% (interquartile range, 50% to 71%) and 79% (interquartile range, 66% to 89%), respectively. For FDG-PET, median sensitivity and specificity were 85% (interquartile range, 67% to 91%) and 90% (interquartile range, 82% to 96%), respectively. Fourteen studies provided information about the conditional test performance of CT and FDG-PET. Positron emission tomography with 18-fluorodeoxyglucose was more sensitive but less specific when CT showed enlarged lymph nodes (median sensitivity, 100% [interquartile range, 90% to 100%]; median specificity, 78% [interquartile range, 68% to 100%]) than when CT showed no lymph node enlargement (median sensitivity, 82% [interquartile range, 65% to 100%]; median specificity, 93% [interquartile range, 92% to 100%]; P = 0.002).

CONCLUSIONS: Positron emission tomography with 18-fluorodeoxyglucose is more accurate than CT for mediastinal staging. Positron emission tomography with 18-fluorodeoxyglucose is more sensitive but less specific when CT shows enlarged mediastinal lymph nodes.

PURPOSE: To evaluate the validity of standard gamble (SG) utilities, by comparing utilities with decision-making behavior in a group of lung transplant candidates facing a risky health decision.

METHODS: The authors elicited SG utilities for current health from 57 transplant candidates. They assessed the concordance between utility scores and patients' self-reported readiness to be placed on the transplant waiting list ("listed"). Because transplantation represents a real-life gamble with a short-term survival probability of 85%, the authors defined their minimum validity criterion as utility for current health < or = 0.85 in transplant-ready patients.

RESULTS: Utilities were significantly higher in patients who were not ready for listing (n = 22, median utility = 0.79, range 0.06-1) than in those who were ready or listed (n = 35, median utility = 0.50, range 0-0.85, P < 0.00005). All transplant-ready patients had utilities < or = 0.85 for current health.

CONCLUSIONS: Low SG utilities were associated with transplant readiness in this population of lung transplant candidates. These results provide one line of evidence supporting the validity of SG utilities as a measure of health-related quality of life, using the criterion of decision-making behavior.

Objective: Most infections occur during childhood, but the health effects of childhood infection are poorly understood. We investigated whether growth decreases in the 2 months after acute seroconversion.

Methods: We performed a nested case-control study among children 6 months to 12 years of age in a community on the outskirts of Lima, Peru. Health interviews were completed daily. Anthropometric measurements were taken monthly. Sera were collected every 4 months and tested for immunoglobulin G. Two-month height and weight gains of seroconverters were compared with gains of sex, age, and size-matched seronegative controls.

Results: In the 2 months after infection, 26 seroconverters gained a median of 24% less weight than 26 matched controls (interquartile range, 63% less to 21% more). In multivariate analysis, infection attenuated weight gain only among children aged 2 years or older. This decrease was not explained by increased diarrhea.

Conclusions: Seroconversion is associated with a slowing of weight gain in children aged 2 years or older. Reasons for this finding merit additional study.