shows patient characteristics for the derivation set (n=54,981), including distribution by gender, age, clinical findings and Centor score. Two-thirds of patients had Centor scores of 1–2, and 68% of patients were female. Thirteen percent of the patients were 15–18 years old. Most patients (91%) had a single encounter, and seven percent had two encounters. In the validation set, the distribution of patients was the same as in the derivation set for age, gender, presence of fever, presence of swollen anterior cervical nodes, absence of cough, presence of tonsillar exudates, and distribution of Centor score. A median number of 7,289 patients were tested per month (IQ range 4365–8602). With regard to volume over time, 29,826 patients were tested in the first quarter of the study, 32,143 in the second, 36,156 in the third, and 34,696 in the fourth. The number of patient-visits, n, for the entire study population were: Georgia 1 (n=7777), Georgia 2 (n=9797), Maryland (n=9720), North Carolina 1 (n=12,236), Indiana (n=8901), Tennessee (n=15,365), North Carolina 2 (n=10,122), Minnesota 1 (n=30,391), and Minnesota 2 (n=27,972).
Clinical characteristics of patients presenting with pharyngitis to the retail health clinics (derivation set: n=54,981 patient-visits)
The proportion of all patients testing positive varied across time and location, demonstrating no obvious predictable GAS pharyngitis season (). For example, during the week of December 24, 2007, the proportion positive in three markets was below 20%, in four was 20–29%, and in two was above 30%. Three, seven, and 14-day RLPPs were strongly correlated (14 vs 7: r2= 0.79, p<0.001, 7 vs 3: r2=0.63, p < 0.001, 14 vs 3, r2= 0.48, p<0.001), so we used 14-day RLPP for subsequent analyses because it provides a realistic time frame to generate reliable, contemporaneous local GAS pharyngitis data.
Proportion positive by study week for nine different locations
Overall, 25% of all patients tested GAS pharyngitis positive in the derivation and validation sets, higher than the 17% in the original Centor study, but comparable to Wigton’s validation study (26%) (11
). For patients with Centor scores 1–4, the proportion testing positive is lowest when the RLPP is low, and increases with rising RLPP (p values for slopes <0.001). illustrates the proportion testing positive plotted by RLPP, grouped by Centor score. Each point on the graph represents a group of patients with an identical Centor score/RLPP dyad. Overall, a patient with a Centor score of 3 is more likely than a patient with a Centor score of 2 to test GAS pharyngitis positive (43% – 25%), but this changes under particular epidemiologic conditions. To illustrate, 350/1053 (33%, 95% CI 30%–36%) patients with a Centor score of 2 test positive when the RLPP is above 0.35, compared to 109/328 (33%, 28%–38%) with a Centor score of 3 when the RLPP is less than 0.15. (see Appendix
) shows a similar graphical distribution for the same analysis using the validation set.
Proportion of patients testing positive for Group A Streptococcal pharyngitis by recent local proportion positive (RLPP) and grouped and labeled by Centor score
We measured the impact of adding one point to a Centor score of 1 when the RLPP exceeded specific thresholds. Hypothetically, testing 1000 patients when the RLPP is > 0.30, for example, would correctly reclassify 139 and incorrectly reclassify 41 patients as positive, a ratio exceeding 3:1 ().
Reclassification Accuracy of Adjusted Centor Score Resulting From Incrementing Score by One Point at Different Thresholds of GAS Pharyngitis Activity
By extrapolation, we estimated that approximately 449,908 of the 10.5 million pharyngitis visits per year, would occur among those 15 years or older, with a Centor score of 1 when the RLPP exceeded 0.30. The biosurveillance approach to guide management of these patients would identify 62,537 additional GAS pharyngitis cases in the U.S. annually, while treating an additional 18,446 patients without GAS pharyngitis. The number needed to test to detect each additional case of GAS pharyngitis is 7.2. (see appendix
) displays the corresponding analyses for the validation set: 60,048 additional cases would be identified, while 18,103 patients without GAS pharyngitis would be treated. In the validation set, the number needed to test is 7.4.
We examined outcomes generated by adding one point to the Centor score of adults and older adolescents with a score of 2 (n=18,942) at specific RLPP cutoffs (). Incrementing the score when the RLPP >0.30 and empirically treating a simulated cohort of 1000 of these patients would correctly reclassify 62 but incorrectly reclassify 657 patients as positive. Extrapolating, this approach correctly identifies 29,450 additional GAS pharyngitis cases in the U.S. annually, but at a cost of inappropriately treating 312,077 patients without GAS pharyngitis.
Next, we tabulated outcomes generated by subtracting one point from the Centor score of all adults and older adolescents with a score of 3 (n=10,056) or 2 (n=18,942) at defined RLPP cutoffs (). Testing 1000 hypothetical patients with a score of 3 when the RLPP < 0.20, rather than treating them empirically would correctly reclassify 620 but incorrectly reclassify 70 patients as negative. In the U.S., this could spare antibiotics for 166,616 patients (5 million doses) while missing only 18,812 cases annually. (appendix
) shows the corresponding data from the validation set: 169,637 patients would be spared antibiotics, while 17,632 patients would be missed.
Reclassification Accuracy of Adjusted Centor Score Resulting From Decreasing Score by One Point at Different Thresholds of GAS Pharyngitis Activity