ACUTE pharyngitis is a common childhood illness. SCIENTIFIC ADVANCES

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1 8 GABHS PREDICTION Attia et al. PREDICTIVE MODELS FOR PEDIATRIC GABHS PHARYNGITIS SCIENTIFIC ADVANCES Multivariate Predictive Models for Group A Beta-hemolytic Streptococcal Pharyngitis in Children MAGDY ATTIA, MD, THEOKLIS ZAOUTIS, MD, STEPHEN EPPES, MD, JOEL KLEIN, MD, FREDERICK MEIER, MD Abstract. Objectives: To create predictive models for the clinical diagnosis of group A beta-hemolytic streptococcal (GABHS) pharyngitis in children. Methods: Patients aged 6 months to 18 years presenting to a pediatric ED with suspected GABHS pharyngitis were prospectively enrolled in the study. Clinicians recorded pertinent clinical information using a standardized form and obtained a throat swab to culture GABHS using a reference standard method. Twelve demographic and clinical features of patients with positive throat cultures were compared with the features of patients with negative throat cultures. Significantly different features were entered in a stepwise logistic regression analysis to create predictive models for the diagnosis. Results: Eighty-five patients (29%) were culture-positive and 212 (71%) were culture-negative for GABHS. Respective mean ages were 6.2 years and 6.1 years in the two groups. Univariate chi-square analysis of the 12 features identified six variables that were significantly associated with GABHS. All significant features were initially included in a stepwise logistic regression analysis. In model I, four independent variables were identified: moderate to severe presentation of tonsillar swelling, moderate to severe tenderness and enlargement of cervical lymph nodes, the presence of scarlatiniform rash, and the absence of moderate to severe coryza, yielding a 95% probability for GABHS. Excluding the rare scarlatiniform rash, the remaining variables were used in the second regression analysis. In model II, three independent variables were identified: moderate to severe tonsillar swelling, moderate to severe tenderness and enlargement of cervical lymph nodes, and absence of moderate to severe coryza, yielding a probability of 65% for the diagnosis. A probability of <15% was observed in the absence of scarlatiniform rash, the absence of moderate to severe tenderness and enlargement of cervical lymph nodes, and the presence of moderate to severe coryza. Conclusions: In children with moderate to severe presentation of tonsillar swelling, tenderness and enlargement of cervical lymph nodes, and the absence of coryza, the probability of a positive throat culture is >65%. Conversely, in the absence of a moderate to severe presentation of tonsillar swelling, enlargement of cervical nodes, and the presence of coryza, the probability of a positive throat culture is <15%. If prospectively validated, these models could be integrated into a consistent treat, test, and no treatment/no testing approach to the clinical management of childhood pharyngitis. Key words: children; group A beta-hemolytic streptococcal; pharyngitis; predictive models. ACA- DEMIC EMERGENCY MEDICINE 1999; 6:8 13 ACUTE pharyngitis is a common childhood illness. Identifying and treating group A betahemolytic streptococcal (GABHS) infection is the From the Departments of Pediatrics (MA, TZ, SE, JK, FM) and Pathology (FM), dupont Hospital for Children, Wilmington, DE; and Thomas Jefferson University, Philadelphia, PA. Received May 27, 1998; revision received August 3, 1998; accepted August 25, Presented at the SAEM annual meeting, Washington, DC, May Supported in part by a grant from the Nemours Foundation. Address for correspondence and reprints: Magdy W. Attia, MD, Emergency Services, dupont Hospital for Children, P.O. Box 269, Wilmington, DE Fax: ; primary goal of clinicians evaluating children with signs and symptoms of pharyngitis. This stems from the well-recognized fact that antibiotic treatment is preventive of suppurative and nonsuppurative complications of streptococcal pharyngitis. 1 4 In addition, early treatment of GABHS pharyngitis shortens the course of the disease. 5 Clinical signs and symptoms of GABHS infection often overlap with those seen with pharyngitis from other etiologies. 6 Some of the same signs and symptoms are seen in adults and children but at different rates. Generally, clinicians tend to overdiagnose this condition. 7 Since the early 1950s, the common approach to suspected GABHS pharyngi-

2 ACADEMIC EMERGENCY MEDICINE January 1999, Volume 6, Number 1 9 tis is to obtain a throat culture 8,9 and more recently, rapid antigen test 8 if available. Laboratory diagnosis of GABHS has many limitations. Throat cultures have a relatively high incidence of false-negative rates (10% 20%) A positive throat culture for GABHS, without serologic evidence, does not distinguish between a carriage state and an acute infection. 14,15 Serologic testing is impractical in the evaluation of suspected acute GABHS pharyngitis. Rapid antigen tests by a reference laboratory method can be highly sensitive; however, the sensitivity varies widely depending on the practice. 13 Hence, the American Academy of Pediatrics recommends their use only in conjunction with throat cultures. 16 On the other hand, culture confirmation of negative high-sensitivity rapid antigen tests is not cost-effective. 17 Other limiting factors for throat cultures are its logistics. Providing patient follow-up and prescribing or discontinuing treatment are cumbersome, particularly in the ED setting. Some clinicians await the culture results and treat those with positive cultures only. Others begin antibiotic therapy at the initial visit. In one report 40% of patients prescribed antibiotics pending culture results were not asked to discontinue antibiotics after a negative culture. 18 In another report, 73% of the pediatric patients with tonsillopharyngitis received antibiotics without a diagnostic test for GABHS. 19 These difficulties in clinical and laboratory diagnosis of GABHS pharyngitis support the argument some emergency physicians (EPs) have for the empirical antimicrobial therapy for patients with reasonable risk for this type of infection. 20 Yet, unnecessary treatment carries a risk for complications without therapeutic benefit 21 and would compound the problem of antimicrobial resistance. The purpose of this study was to derive a simple clinical tool to assist in the clinical management of GABHS pharyngitis in children. METHODS Study Design. This was a prospective clinical study of children with suspected GABHS pharyngitis. Comparisons were made between children with positive throat cultures and those with negative throat cultures, and significantly different features were entered into a stepwise logistic regression analysis to create predictive models for the diagnosis. This study was reviewed and approved by the institutional review board. Study Setting and Population. Children aged 6 months to 18 years who presented with pharyngitis and received a throat culture based on the clinical suspicion of GABHS by the EP were prospectively included. The study was conducted at the ED of a university-affiliated children s hospital between January 21, 1996, and April 30, Children who had recently used antibiotics (within five days of presentation) and those who had been previously enrolled in the study were excluded. Study Protocol and Measurements. At the time of presentation, 12 demographic and clinical variables describing the eligible patients were collected by the EP using a standardized data collection form. Age and temperature were recorded as continuous numerical variables. To allow a measurement of severity, five clinical features were recorded as defined ranked variables; none, mild, moderate, or severe. These features included: tonsillar/pharyngeal exudate, tonsillar swelling, pharyngeal erythema, coryza, and tenderness and enlargement of cervical lymph nodes. Five additional features were recorded as dichotomous variables (absent or present). These were: scarlatiniform rash, halitosis, headache, palatine petechiae, and abdominal pain. Clinicians were instructed to swab the posterior oropharyngeal wall and the tonsillar pillars, including the upper portions of the tonsils bilaterally. This technique was illustrated on the data collection form. A rayon-tipped culture swab (Culturettes, Becton-Dickinson Microbiology Systems, Cockeysville, MD) was used to collect each specimen. After collection, the transport media of the culture swab was activated. Specimens were transported to the hospital laboratory immediately. The swab was then plated on two Strep-Selective Agar media (Remel Inc., Lenexa, KS). Plates were incubated anaerobically and examined at 24 hours and 48 hours for beta-hemolytic colonies. Beta-hemolytic isolates from these colonies were subcultured onto fresh sheep blood agar for identification of GABHS by the PathoDX Latex Agglutination Kit (DPC Diagnostics, Los Angeles, CA). Data Analysis. All information was entered into a Microsoft Excel 5.0 database (Seattle, WA). Data were analyzed using the SAS statistical system (Cary, NC). An overall analysis of variance of continuous and ranked variables was performed. Ranked variables were also dichotomized into two groups: none/mild and moderate/severe. Categorical and dichotomized variables on all subjects were analyzed by two-tailed chi-square test. Odds ratios and 95% confidence intervals were calculated for all variables. Variables that met the 0.05 significant probability level in the univariate analysis and had complete clinical data entries for all dependent and independent variables were entered into a stepwise multiple logistic regression analysis to create the predictive models. First, all six

3 10 GABHS PREDICTION Attia et al. PREDICTIVE MODELS FOR PEDIATRIC GABHS PHARYNGITIS TABLE 1. Clinical Features of Group A Beta-hemolytic Streptococcus (GABHS)-positive Patients and GABHS-negative Patients Clinical Feature ( )GABHS* (n = 85) ( )GABHS* (n = 212) Sensitivity Specificity Odds Ratio 95% CI p-value Age <5 years 38 (45%) 118 (56%) 24% 67% , Temperature >38 C 45 (53%) 124 (59%) 30% 70% , Tonsillar/pharyngeal exudate 36 (42%) 76 (36%) 32% 74% , Tonsillar swelling 43 (54%) 59 (29%) 33% 80% , Pharyngeal erythema 48 (60%) 69 (35%) 29% 78% , Tender, enlarged cervical nodes 67 (78%) 124 (58%) 35% 83% , Absence of coryza 54 (64%) 97 (45%) 21% 64% , Scarlatiniform rash 12 (14%) 7 (3%) 63% 75% , Halitosis 18 (22%) 24 (12%) 43% 75% , Headache 27 (33%) 53 (26%) 34% 74% , Palatine petechiae 13 (17%) 17 (9%) 43% 73% , Abdominal pain 21 (25%) 69 (34%) 23% 69% , *Number of subjects with feature and percentage. Moderate to severe presentation. significant clinical features were used to create model I. Model II was created by regression analysis of the same variables, excluding the feature of scarlatiniform rash because of its rarity as a component of patients clinical presentation. RESULTS Demographics, Culture Results, and Clinical Features of GABHS. Three hundred twenty-four patients with suspected GABHS pharyngitis were enrolled in the study. Twenty-seven patients were excluded; 23 for antibiotic use within five days of presentation and four for being previously enrolled in the study. Of the included 297 patients, 34 had incomplete clinical data entries. Mean age SD for patients was 6.2 years ( 4.2) (range: 9 months to 18 years). Fifty-two percent were male. Eighty-five patients (29%) were culture-positive for GABHS, 212 (71%) were negative for GABHS. Of the 34 patients with incomplete clinical data, eight (28%) were culturepositive and 26 (72%) were culture-negative. Respective mean ages for the culture-positive and the culture-negative patients were 6.2 years ( 3.4) and 6.1 years ( 4.6). When patients were stratified by age, GABHS was more prevalent in school-aged children (ages 6 11 years) than in the preschool age group (0.5 5 years) (39% vs 24%, p = 0.05) and adolescents (12 to 18 years) (39% vs 19%, p = 0.05). The prevalences of GABHS, however, were not different between children 5 years of age or younger (0.5 5 years) and children older than 5 years of age (6 18 years) (24% vs 33%, p = 0.11). A comparison of the clinical features in GABHS throat culture-positive patients and those in GABHS throat culture-negative patients is shown in Table 1. All six clinical features significantly associated with GABHS were initially included in a stepwise logistic regression analysis to produce model I. Four independent variables were identified as predictors of the diagnosis. These variables were: scarlatiniform rash, moderate to severe tonsillar swelling, moderate to severe tenderness and enlargement of cervical lymph nodes, and absence of moderate to severe coryza. In the presence of these signs, the probability for GABHS was 95%. Excluding the relatively rare scarlatiniform rash, the remaining variables were used in the second regression analysis. Moderate to severe tonsillar swelling, moderate to severe tenderness and enlargement of cervical nodes, and absence of moderate to severe coryza were identified as independent variables associated with GABHS, with a probability of 65% for the diagnosis in model II. In the presence of moderate to severe coryza and the absence of scarlatiniform rash and moderate to severe tenderness and enlargement of cervical nodes, the probability of GABHS fell to less than 15%. Pharyngeal erythema and halitosis did not add to the predictive ability in either model. A range of probabilities for GABHS between 15% and 65% can be identified based on the absence of scarlatiniform rash and one or more other variables. Beta values, odds ratios, confidence intervals, and p-values for the independent variables in the two models are shown in Table 2. Power was computed for models I and II. Using a p < 0.05, four and three predictors, respectively, a total sample size of 263, and a medium effect size (i.e., f = 0.15), power for the logistic regression analysis of both models was 0.99.

4 ACADEMIC EMERGENCY MEDICINE January 1999, Volume 6, Number 1 11 DISCUSSION TABLE 2. Independent Variables in Both Predictive Models Clinical Variable Beta Odds Ratio 95% CI p-value Model I (GABHS* probability 95%) Scarlatiniform rash , Tonsillar swelling , Tender, enlarged cervical nodes , Absence of coryza , Model II (GABHS probability 65%) Tonsillar swelling , Absence of coryza , Tender, enlarged cervical nodes , *GABHS = group A beta-hemolytic streptococcus. Moderate to severe presentation. The findings in our study suggest that some of the widely cited clinical features of GABHS pharyngitis in children (fever, tonsillar or pharyngeal exudates, palatine petechiae, abdominal pain, and headache 1,22 ) did not discriminate between GABHS pharyngitis and pharyngitis from other causes. Two other recent studies support the nondiscriminating nature of these features. 23,24 Our data also indicate that the incidence of some of the clinical features of GABHS pharyngitis in children differ from those for adults. Centor et al. found tonsillar exudates and fever to be associated with GABHS pharyngitis in adults. 25 This association was not observed in the pediatric patients in the current study. The prevalence of GABHS pharyngitis we reported is similar to that in other reports. 15,23 The age cohort used in the data analysis ( preschoolaged, school-aged, and adolescent) is practical and commonly used to describe subsets of a pediatric population. Young age (less than 5 years) was not a factor that influenced culture outcome in children presenting with pharyngitis. The prevalence of GABHS in the school-aged children (6 11 years) remains highest (39% [vs overall prevalence of 29%]). It is noteworthy that the prevalence of GABHS sharply declined to 11% (four of 37 patients) in children less than 2 years of age. This lower rate is, however, significantly higher than the previously reported rate of 5%. 26,27 It has been suggested to not test for GABHS in patients with pharyngitis if the probability for the disease is low. 28,29 We reason that a probability of less than the carriage rate in a population is a point at which the child with acute pharyngitis could be excluded from testing for GABHS. Likewise, the Figure 1. Clinical decision making chart for prospective validation. 1 Moderate-to-severe presentation. 2 Rapid antigen test and/or throat culture.

5 12 GABHS PREDICTION Attia et al. PREDICTIVE MODELS FOR PEDIATRIC GABHS PHARYNGITIS child with predictive signs can be empirically treated. Many algorithms 23,24 and scores 30,31 have been devised in an attempt to increase the clinical accuracy of the diagnosis of GABHS pharyngitis in children. However, utility of these clinical tools has been limited due to their complexity. 23,24,30,31 On the other hand, much simplified clinical guidelines such as the ones produced by the World Health Organization for use by health care professionals in developing countries have been shown to have low sensitivity. 32 Our data have enabled us to devise a clinical decision making chart (Fig. 1). The data used included ranked variables, inherently containing a measurement of severity, therefore yielding a better predictive ability. We also believe that dichotomizing these ranked variables as none/ mild and moderate/severe can only increase the predictive ability of the models because it diminishes the chances of overcalling the clinical stigmata. As discussed earlier, GABHS pharyngitis is overdiagnosed. This clinical tool is simple and not age-dependent. It allows clinicians to estimate the probability for culture result based on specific clinical criteria. This may be useful in the busy practice setting and especially where follow-up of patients with pending culture results is unreliable. LIMITATIONS AND FUTURE QUESTIONS Though our study sample was drawn from a pediatric ED over a limited period of time, it appears to represent the typical pediatric pharyngitis population with regard to age and sex distribution. Hence, generalization of utilization of the clinical decision making chart is plausible. However, its immediate application is limited by the lack of prospective validation. We plan to test these models in different practice settings and time periods. Another relative limitation of the study is the lack of interobserver reliability test. This limitation is diminished by using the classic grouping of absent, mild, moderate, and severe in scoring the ranked variables. CONCLUSIONS The study demonstrated that some of the clinical findings traditionally enumerated to be associated with streptococcal pharyngitis did not distinguish between patients with positive cultures and patients with negative cultures for GABHS. More importantly, the study identified four clinical variables integrated into two predictive models. These two models had significantly better predictive abilities for both positive (>65%) and negative (<15%) diagnoses of GABHS than the common teaching that this diagnosis is made accurately based on clinical findings in only 50% of patients. Using these models, children presenting with suspected GABHS pharyngitis can be divided into three groups based on their risk for positive throat culture: a high-risk group, probability >65%; a moderate-risk group, probability between 15% and 65%; and a low-risk group, probability <15%. If prospectively validated, clinicians may use these probability estimates as guidelines to warrant empirical treatment, selective testing, or neither for children with suspected GABHS pharyngitis. The authors are indebted to Mr. Michael Rossi and to Dr. Joseph Glutting for their enthusiastic help with the statistical analysis of the data and to Mrs. Michelle Stofa for her help with manuscript preparation and editing. References 1. Shulman ST. Streptococcal pharyngitis: diagnostic considerations. Pediatr Infect Dis J. 1994; 13: Denny FW, Wannamaker LW, Brink WR, Rammelkamp CH Jr, Custer EA. Prevention of rheumatic fever; treatment of preceding streptococci infection. JAMA. 1950; 143: Dajani AS, Bisno AL, Chung KJ, et al. Prevention of rheumatic fever. A statement for health professionals by the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 1988; 78: Shulman ST. Pharyngitis: Management in an Era of Declining Rheumatic Fever. New York, NY: Praeger Publishers, Martin FR, Gerber MA, DeMeo KK, Wright L. Effect of antibiotic therapy on the clinical course of streptococcal pharyngitis. J Pediatr. 1985; 106: Wannamaker LW. Diagnosis of pharyngitis: clinical and epidemiologic features. In: Shulman ST (ed). Pharyngitis: Management in an Era of Declining Rheumatic Fever. New York, NY: Praeger Publishers, 1984, pp Poses RM, Cebul RD, Collins M, Fager SS. The accuracy of experienced physicians probability estimates for patients with sore throats. Implications for decision making. JAMA. 1985; 254: Schwartz B, Fries S, Fitzgibbon AM, Lipman H. Pediatricians diagnostic approach to pharyngitis and impact of CLIA 1988 on office diagnostic tests. JAMA. 1994; 271: Breese BB, Disney FA. Accuracy of diagnosis of beta streptococcal infection on clinical grounds. J Pediatr. 1954; 44: Centor RM, Meier FA, Dalton HP. Throat cultures and rapid tests for diagnosis of group A streptococcal pharyngitis. Ann Intern Med. 1986; 105: Rosenstein BJ, Markowitz M, Gordis L. Accuracy of throat cultures in physicians offices. J Pediatr. 1970; 76: Battle CU, Glasgow LA. Reliability of bacteriological identification of beta-hemolytic streptococci in private offices. Am J Dis Child. 1971; 122: Gerber MA, Tanz RR, Kabat W, et al. Optical immunoassay test for group A beta-hemolytic streptococcal pharyngitis. An office-based, multicenter investigation. JAMA. 1997; 277: Wannamaker LW. Perplexity and precision in the diagnosis of streptococcal pharyngitis. Am J Dis Child. 1972; 124: Kaplan EL, Top FH Jr, Dudding BA, Wannamaker LW. Diagnosis of streptococcal pharyngitis: differentiation of active infection from the carrier state in the symptomatic child. J Infect Dis. 1971; 123: American Academy of Pediatrics. Group A Streptococcal Infections. In: Peter G (ed) Redbook. Report of the Committeee on Infectious Diseases, 24th Ed. Elk Grove Village, IL:

6 ACADEMIC EMERGENCY MEDICINE January 1999, Volume 6, Number 1 13 American Academy of Pediatrics, 1997, p Webb KH. Does culture confirmation of high-sensitivity rapid streptococcal tests make sense? A medical decision analysis. Pediatrics. 1998; 101(e2): Cochi SL, Fraser DW, Hightower AW, Facklam RR, Broome CV. Diagnosis and treatment of streptococcal pharyngitis: survey of US medical practitioners. In: Shulman ST (ed). Pharyngitis: Management in an Era of Declining Rheumatic Fever. New York, NY: Praeger Publishers, 1984, pp Mainous AG 3rd, Zoorob RJ, Kohrs FP, Hagen MD. Streptococcal diagnostic testing and antibiotics prescribed for pediatric tonsillopharyngitis. Pediatr Infect Dis J. 1996; 15: Green SM. Acute pharyngitis: the case for empiric antimicrobial therapy. Ann Emerg Med. 1995; 5: Lieu TA, Fleisher GR, Schwartz JS. Cost effectiveness of rapid latex agglutination testing and throat culture for streptococcal pharyngitis. Pediatrics. 1990; 85: Tanz RR, Shulman ST. Diagnosis and treatment of group A streptococcal pharyngitis. Sem Pediatr Infect Dis. 1995; 6: Edmond MK, Grimwood K, Carlin JB, Chondros P, Hogg GG, Barnett PL. Streptoccocal pharyngitis in a pediatric emergency department. Med J Aust. 1996; 165: Meland E, Digranes A, Skjaerven R. Assessment of clinical features predicting streptococcal pharyngitis. Scand J Infect Dis. 1993; 25: Centor RM, Witherspoon JM, Dalton HP, Brody CE, Link K. The diagnosis of strep throat in adults in the emergency room. Med Decis Making. 1981; 1: Levin RM, Grossman M, Jordan C, Ticknor W, Barnett P, Pascoe D. Group A streptococcal infection in children younger than three years of age. Pediatr Infect Dis J. 1988; 7: Amir J, Shechter Y, Eilam N, Varsano I. Group A betahemolytic streptococcal pharyngitis in children younger than 5 years. Isr J Med Sci. 1994; 30: Tompkins RK. A management strategy for sore throat based on cost effectiveness analysis. In: Lasagna L (ed). Controversies in Therapeutics. Philadelphia, PA: W. B. Saunders, 1980, pp Komaroff AL, Pass TM, Aronson MD, et al. The prediction of streptococcal pharyngitis in adults. J Gen Intern Med. 1986; 1: Breese BB. A simple scorecard for the tentative diagnosis of streptococcal pharyngitis. Am J Dis Child. 1977; 131: Randolph MF, Redys JJ, Hibbard EW. Streptococcal pharyngitis. I. Correlation of cultures with clinical criteria. De Med J. 1970; 42: Steinhoff MC, Abd El Khalek MK, Khallaf N, et al. Effectiveness of clinical guidelines for the presumptive treatment of streptococcal pharyngitis in Egyptian children. Lancet. 1997; 350: Instructions for Contributors to Off the Shelf Off the Shelf is a section in Academic Emergency Medicine comprised of media reviews. AEM manuscript submission requirements correspond with the uniform requirements for manuscripts submitted to biomedical journals (JAMA. 1997; 277:927 34). Solicited media reviews should be sent to the SAEM Editorial Office (address below) and should be accompanied by a copyright and author disclosure form that has been reviewed and signed and an electronic copy on a computer disk. Any word processing program is acceptable for this submission; the type of processing program should be indicated on the label of the disk. Send three hard copies and the electronic version of the media review to: Academic Emergency Medicine, Society for Academic Emergency Medicine, 901 North Washington Avenue, Lansing, MI Phone: (517) ; fax: (517) ; saem@saem.org. Media reviews should be no longer than six doublespaced, typewritten pages. Appropriate references can be incorporated if needed. Media reviews should be written in language that conforms to accepted English usage and syntax. Avoid slang, medical jargon, and obscure abbreviations. Generic drug names should be used unless the trade name is relevant. The author of a media review should incorporate into the title page of the manuscript information relative to the source of the text or other product under review. For example, in the case of textbooks, the title, authors, publisher, site of publication, cost, and length of the book should be listed. The content of the review is left to the discretion of the reviewer. However, the following outline is offered for consideration: 1. Introduction briefly describe the overall purpose of the media under review, its intended audience, and the approach that is used to deliver its message. 2. Describe how the information is delivered. For instance, some textbooks are divided into sections, each of which can be critiqued separately. 3. Discuss the strong points and the weaknesses of the product under review. Is it truely relevant, does it serve a need, is it unique, and how could it be improved? 4. Determine whether the authors have achieved their stated purpose or aim. 5. Indicate whether you believe this is a valuable addition to the specialty of emergency medicine. Describe how it can be applied and where its shortfalls are. These suggestions are offered as guidelines only. The author of a media review may use another approach in writing the review so long as the final manuscript represents a balanced critique of the product under review. If you have any specific questions regarding the development of a media review for Academic Emergency Medicine, please contact the Editor-in-Chief of Academic Emergency Medicine, Michelle Biros, MS, MD, at (612)

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