Faculty Bibliography

BACKGROUND:Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis. METHODS:We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith. RESULTS:In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50). CONCLUSIONS:For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.).

Introduction: Management of acetaminophen (APAP) toxicity is heavily reliant on the plasma or serum concentration. We sought to determine the analytical characteristics of past and current commercial APAP assays in the United States.
Method(s): We systematically reviewed the analytical characteristics of APAP assays cleared by the Food and Drug Administration's (FDA) 510(k) premarket notification process by searching the Clinical Laboratory Improvement Amendments (CLIA) database. If no analytical data were available, we contacted the manufacturer directly and searched for peer reviewed reports. We excluded non-blood assays, qualitative assays, and assays for which precision data were not available. We collected the following data where available: test principle, precision near 10mg/L, precision near 150 mg/L, limits of detection, and limits of quantitation. Accuracy and specificity were not routinely reported and outside the scope of this study.
Result(s): From 212 search results, we identified 19 different assays derived from 15 parent devices (Figure 1). All extracted analytical characteristics are shown in Table 1. Twelve were enzymatic while 7 were immunoassays. For all assays, absolute analytical precision decreased as analyte concentration increased (Figure 1). Near [APAP]=10mg/L, the most precise assays had a standard deviation (SD) of 0.2 mg/L or coefficient of variation (CV=SD/mean) of 1% and the least precise assays had a SD of range of 1.8mg/L or a CV of 10%. Near [APAP]=150 mg/L, the most precise assay had a SD of 1.4 mg/L or CV of 0.9% and the least precise assays had a SD of 7.4mg/L or a CV of 4.9%. Some manufacturers failed to validate assay precision at or near clinically- relevant [APAP]: two assays did not have precision data for [APAP]<40 mg/L, eight assays did not have precision data for [APAP]>150mg/L. The limit of detection ranged from 0.1- 2.4mg/L. The lower limit of quantitation ranged from 0.6-10mg/ L. The upper limit of quantitation ranged from 200-380 mg/L, before dilution.
Conclusion(s): APAP assays uncovered by our search had good analytical precision with improvement over time. The failure of some manufacturers to validate precision near treatment thresholds is concerning. Newer APAP assays could quantify lower [APAP], raising the likelihood of overdiagnosis and subsequent overtreatment. The FDA CLIA database for 510(k) devices is limited by redundant entries and incomplete data but remains a freely accessible starting point for clinicians to learn about many toxicologic assays. These data are not a substitute for independent laboratory optimization and validation.