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Dog bites in children
Correspondence DOG BITES IN CHILDREN To the Editor:-There is a host of management problems in emergency medicine where methodologically sound, prospective clinical studies are needed. One such problem is the use of prophylactic antibiotic therapy and the role of initial wound cultures in the management of dog bites. While the article by Boenning et al’ addresses these management problems in children, we should like to raise several problems with this study. One question concerns the failure to “blind” patients, allowing for the introduction of bias and a systematic difference in the treatment of study groups. Effects resulting from a lack of equal treatment are amply documented. 1 In this study, several such differences in treatment are noted. Only the experimental group received a pill (penicillin), with measures taken to assure a high degree of compliance. The control group did not receive a placebo. This resulted in different discharge instructions for the control and experimental groups. In addition no mention is made of any follow-up phone instructions given the control group. In compliance with the Zelen protocol,3 only the experimental group was required to sign informed consent. This promotes the Hawthorne effect,2*4 which is a systematic change in behavior that results merely as a function of being observed in an experiment. While one cannot predict whether it will augment or diminish the true outcome, a change in behavior can be expected that is measurably different from the behavior of a subject unaware of being observed.4 The study group receiving only local wound care did not sign informed consent. It is possible, therefore, that the control subjects were unaware that a study was taking place. Accordingly, the Hawthorne effect was present and was not applied equally across the study groups. The physicians and nurses were not “blinded.” One’s investment in the results or anticipation of how subjects are likely to respond can easily become a selffulfilling prophecy.*y5 This effect is not consciously noted or easily neutralized through volition. This bias may have been in effect during discharge and followup instructions, during outcome assessment, or during the wound cleaning itself, to subtly influence the patient’s management of the wound and therefore alter the true outcome. While patients were randomized into treatment groups based on presentation on odd or even days, Gifford and Feinstein6 have shown that unexpected bias can be introduced even in such a seemingly random schedule. Though house officers and nurses did not work on alternate day schedules, this does not
assure true randomization. With this schedule, several patients may have presented on the same day or even the same shift. It is conceivable that these patients were treated by the same house offtcer, whose surgical technique of wound cleaning and debridement was superior, thereby unduly influencing a small group. Conversely, such technique may have been inferior, but performed on patients assigned to the antibiotic group. A random numbers table or a computer-generated scheme avoids these pitfalls. The study design may also be open to the problem of competing interventions.* Nine per cent (5/S) of the patients had wound site swelling but did not otherwise meet the criteria for infection. The authors indicate that all these patients came from the control group, as “. . . swelling resolved . . . without antibiotic therapy.” Accordingly, this constitutes about 17% (5/30) of the control group. It would have been helpful to know if these patients were given additional therapy (splinting, the application of heat, elevating the extremity, the use of soaks, and so on). Any of these co-interventions could have influenced the outcome in such a way that full infections would otherwise have developed in those patients. The authors also report that three patients were lost to follow-up but do not indicate which study group they come from. When information on follow-up is lost, a “bad outcome” should be assigned to all members of the group, and the data reconsidered in this light.’ If all three patients were in one arm of the study, the outcome and its interpretation could be different. The statistical significance would not change if all lost patients were to be considered as infected and from the control group. Nonetheless, a 4% (l/25) versus a 13% (4/30) infection rate might be considered clinically significant. The authors note that a larger sample size would have been needed to show a statistically significant difference. If one considers that competing interventions may have influenced the five patients with early signs of infection (wound swelling only), it is conceivable that by assigning a “bad outcome” to this group also, the infection rate could have been as high as 30% (9/30) (one patient infected, three lost to follow-up, and five with wound site swelling) and statistically significant. However, given the small sample size, the loss to follow-up, and the potential problem of competing interventions, further trials seen warranted. Information on the socio-demographic status of the families would have been helpful. The efficacy of a treatment may be dependent on the demographic characteristics of the population studied, including timing of presentation.8 In the study by Boenning et al,’ the majority of patients presented within one hour of in111
AMERICAN
JOURNAL
OF EMERGENCY
n Volume 2, Number
MEDICINE
jury. This may not reflect current emergency department experience elsewhere, and the authors furnish us with data in support of this contention.9 In Goldstein’s study, 50% of the patients presented within the first eight hours. This may be significantly different (clinically) than the presentation of a majority of patients with one hour in this study. Furthermore, cultures taken within one hour may grow different pathogens than wound cultures taken eight hours or later after the injury. The authors also conclude that “initial cultures of dog bite wounds have no value in predicting subsequent wound infection.” However, of two patients in this study in whom wound infections developed, only one patient received both an initial and a follow-up culture. The other patient had only one culture, taken after the infection developed. Accordingly, the conclusion that initial wound cultures have no predictive value in determining the organism responsible for subsequent wound infection is based on a sample of one. While the authors conclude that no difference was found between the control and experimental groups, by elimination of the methodologic biases given above, a significant difference in outcome may have been missed. GABOR D. KELEN. MD
Department of Emergency Medicine The Johns Hopkins Hospital Baltimore, Maryland CHARLES G. BROWN, MD
Division of Emergency Ohio State University Columbus, Ohio
Medicine
References 1. 2. 3. 4. 5. 6.
7. 8.
9.
Boenning DA, Fleisher GR, Campos JM. Dog bites in children: Epidemiology, microbiology, and penicillin prophylactic therapy. Am J Emerg Med 1983;1:17-21. Gehlbach SH. Interpreting the Medical Literature: A Clinician’s Guide. Lexington Mass: DC Heath 8 Co, 1981. Zelen M. A new design for randomized clinical trials. N Engl J Med 1979;300:1242-1246. Drew CJ. Introduction to Designing Research and Evaluation. St. Louis: C.V. Mosby, 1976. Rosenthal R. Experimenter Effects in Behavioral Research. New York: Appleton Century Crofts, 1968. Gifford RH, Feinstein AR. A critique of methodology in studies of anticoagulant therapy for acute M.I. N Engl J Med 1969;280:351-357. Sackett DL, et al. How to read clinical journals. Can Med Assoc J 1981;124:1156-1162. Rubin RH, Fang LST, Jones SR, et al. Single-dose amoxicillin therapy for urinary tract infection: Multicenter trial using antibody-coated bacteria localization technique. JAMA 1980;244:561-564. Goldstein EJC, Citron DM, Finegold SM. Dog bite wounds and infection: A prospective clinical study. Ann Emerg Med 1980;9:508-512.
The authors reply:- We appreciate the interest shown in our study by Drs. Kelen and Brown. In clinical 112
1
research, there are advantages and disadvantages of any study design. The major advantage of the Zelen design is that it maximizes patient enrollment.’ By contrast, in the conventional trial, patients who refuse consent are lost to study, even though they receive routine therapy. Most conventional trials have an inherent selection bias, since only those patients who have consented for study are followed up. Untold numbers of patients may be lost to study because they were never enrolled in the first place. One widely quoted study in the field of animal bites includes follow-up data on only 10% of the original sample.* Our follow-up rate of eligible patients is 95% (55 out of 58 patients)-an excellent rate for a clinical study. Of the three patients lost to follow-up, two belonged to the experimental group and one belonged to the control group. Drs. Kelen and Brown raise questions about potential methodologic biases but miss the forest for the trees. If we had claimed a difference between the experimental and control groups, these potential biasesnonblinding, lack of placebo, Hawthorne effect, and alternate day assignment-would raise serious concerns. However, infections developed in only two of the 55 patients in the study, one in each group. The incidence of infection is so low that the theoretic arguments put forth by Drs. Kelen and Brown are not relevant. Furthermore, the results of any patient assignment method, whether random or otherwise, should be scrutinized to determine whether equivalent groups are achieved, as demonstrated in Table 1 of our paper. Regarding the median time of delay between the biting incident and presentation to the emergency department, we cannot make our patients simulate the results reported in other studies of adult patients. The point of the smaller median time delay in children is that parents perceive a dog bite in their child as a medical emergency and consequently respond quickly. Finally, in an era of high medical costs, the need for prudent use of the laboratory is self-evident. The positive predictive value of initial wound cultures was zero (no infections out of 14 wound cultures with potential pathogens). Of the 35 cultures submitted from fresh bite wounds, none would have been helpful in the management of the patient. DOUGLAS A. BOENNING, MD GARY R. FLEISHER, MD JOSEPHM. CAMPOS, PHD
The Children’s Hosaital of Philadelphia Philadelphia, Pennsylvanl’a
References 1. Zelen M. A new design for randomized clinical trials. N Engl J Med 1979;300:1242-1246. 2. Callaham M. Prophylactic antibiotics in common dog bite wounds: A controlled study. Ann Emerg Med 1980;9:410414.
assure true randomization. With this schedule, several patients may have presented on the same day or even the same shift. It is conceivable that these patients were treated by the same house offtcer, whose surgical technique of wound cleaning and debridement was superior, thereby unduly influencing a small group. Conversely, such technique may have been inferior, but performed on patients assigned to the antibiotic group. A random numbers table or a computer-generated scheme avoids these pitfalls. The study design may also be open to the problem of competing interventions.* Nine per cent (5/S) of the patients had wound site swelling but did not otherwise meet the criteria for infection. The authors indicate that all these patients came from the control group, as “. . . swelling resolved . . . without antibiotic therapy.” Accordingly, this constitutes about 17% (5/30) of the control group. It would have been helpful to know if these patients were given additional therapy (splinting, the application of heat, elevating the extremity, the use of soaks, and so on). Any of these co-interventions could have influenced the outcome in such a way that full infections would otherwise have developed in those patients. The authors also report that three patients were lost to follow-up but do not indicate which study group they come from. When information on follow-up is lost, a “bad outcome” should be assigned to all members of the group, and the data reconsidered in this light.’ If all three patients were in one arm of the study, the outcome and its interpretation could be different. The statistical significance would not change if all lost patients were to be considered as infected and from the control group. Nonetheless, a 4% (l/25) versus a 13% (4/30) infection rate might be considered clinically significant. The authors note that a larger sample size would have been needed to show a statistically significant difference. If one considers that competing interventions may have influenced the five patients with early signs of infection (wound swelling only), it is conceivable that by assigning a “bad outcome” to this group also, the infection rate could have been as high as 30% (9/30) (one patient infected, three lost to follow-up, and five with wound site swelling) and statistically significant. However, given the small sample size, the loss to follow-up, and the potential problem of competing interventions, further trials seen warranted. Information on the socio-demographic status of the families would have been helpful. The efficacy of a treatment may be dependent on the demographic characteristics of the population studied, including timing of presentation.8 In the study by Boenning et al,’ the majority of patients presented within one hour of in111
AMERICAN
JOURNAL
OF EMERGENCY
n Volume 2, Number
MEDICINE
jury. This may not reflect current emergency department experience elsewhere, and the authors furnish us with data in support of this contention.9 In Goldstein’s study, 50% of the patients presented within the first eight hours. This may be significantly different (clinically) than the presentation of a majority of patients with one hour in this study. Furthermore, cultures taken within one hour may grow different pathogens than wound cultures taken eight hours or later after the injury. The authors also conclude that “initial cultures of dog bite wounds have no value in predicting subsequent wound infection.” However, of two patients in this study in whom wound infections developed, only one patient received both an initial and a follow-up culture. The other patient had only one culture, taken after the infection developed. Accordingly, the conclusion that initial wound cultures have no predictive value in determining the organism responsible for subsequent wound infection is based on a sample of one. While the authors conclude that no difference was found between the control and experimental groups, by elimination of the methodologic biases given above, a significant difference in outcome may have been missed. GABOR D. KELEN. MD
Department of Emergency Medicine The Johns Hopkins Hospital Baltimore, Maryland CHARLES G. BROWN, MD
Division of Emergency Ohio State University Columbus, Ohio
Medicine
References 1. 2. 3. 4. 5. 6.
7. 8.
9.
Boenning DA, Fleisher GR, Campos JM. Dog bites in children: Epidemiology, microbiology, and penicillin prophylactic therapy. Am J Emerg Med 1983;1:17-21. Gehlbach SH. Interpreting the Medical Literature: A Clinician’s Guide. Lexington Mass: DC Heath 8 Co, 1981. Zelen M. A new design for randomized clinical trials. N Engl J Med 1979;300:1242-1246. Drew CJ. Introduction to Designing Research and Evaluation. St. Louis: C.V. Mosby, 1976. Rosenthal R. Experimenter Effects in Behavioral Research. New York: Appleton Century Crofts, 1968. Gifford RH, Feinstein AR. A critique of methodology in studies of anticoagulant therapy for acute M.I. N Engl J Med 1969;280:351-357. Sackett DL, et al. How to read clinical journals. Can Med Assoc J 1981;124:1156-1162. Rubin RH, Fang LST, Jones SR, et al. Single-dose amoxicillin therapy for urinary tract infection: Multicenter trial using antibody-coated bacteria localization technique. JAMA 1980;244:561-564. Goldstein EJC, Citron DM, Finegold SM. Dog bite wounds and infection: A prospective clinical study. Ann Emerg Med 1980;9:508-512.
The authors reply:- We appreciate the interest shown in our study by Drs. Kelen and Brown. In clinical 112
1
research, there are advantages and disadvantages of any study design. The major advantage of the Zelen design is that it maximizes patient enrollment.’ By contrast, in the conventional trial, patients who refuse consent are lost to study, even though they receive routine therapy. Most conventional trials have an inherent selection bias, since only those patients who have consented for study are followed up. Untold numbers of patients may be lost to study because they were never enrolled in the first place. One widely quoted study in the field of animal bites includes follow-up data on only 10% of the original sample.* Our follow-up rate of eligible patients is 95% (55 out of 58 patients)-an excellent rate for a clinical study. Of the three patients lost to follow-up, two belonged to the experimental group and one belonged to the control group. Drs. Kelen and Brown raise questions about potential methodologic biases but miss the forest for the trees. If we had claimed a difference between the experimental and control groups, these potential biasesnonblinding, lack of placebo, Hawthorne effect, and alternate day assignment-would raise serious concerns. However, infections developed in only two of the 55 patients in the study, one in each group. The incidence of infection is so low that the theoretic arguments put forth by Drs. Kelen and Brown are not relevant. Furthermore, the results of any patient assignment method, whether random or otherwise, should be scrutinized to determine whether equivalent groups are achieved, as demonstrated in Table 1 of our paper. Regarding the median time of delay between the biting incident and presentation to the emergency department, we cannot make our patients simulate the results reported in other studies of adult patients. The point of the smaller median time delay in children is that parents perceive a dog bite in their child as a medical emergency and consequently respond quickly. Finally, in an era of high medical costs, the need for prudent use of the laboratory is self-evident. The positive predictive value of initial wound cultures was zero (no infections out of 14 wound cultures with potential pathogens). Of the 35 cultures submitted from fresh bite wounds, none would have been helpful in the management of the patient. DOUGLAS A. BOENNING, MD GARY R. FLEISHER, MD JOSEPHM. CAMPOS, PHD
The Children’s Hosaital of Philadelphia Philadelphia, Pennsylvanl’a
References 1. Zelen M. A new design for randomized clinical trials. N Engl J Med 1979;300:1242-1246. 2. Callaham M. Prophylactic antibiotics in common dog bite wounds: A controlled study. Ann Emerg Med 1980;9:410414.