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1
Volmne 176, Number 2 Letters 495 AmJ Obstet Gynecol statistical design of this retrospective analysis that signif- icantly limits the results and conclusions. First, the au- thors have performed artificial categorization by separat- ing patients into Quetelet index <30, 30 to 40, and >40. This is a common and unacceptable statistical flaw. 1 Because Quetelet index values comprise a continuous numeric scale, patients should be analyzed according to the specific Quetelet index and comparisons should be made along a numeric distribution statistic, such as a t test, rather than artificial categorization and compari- sons with Pearson's X 2. The second major statistical flaw is that the conclu- sions are not based on the data presented. The last conclusion is that in morbidly obese patients lack of lymph node sampling does not adversely affect survival. In this study there were only 38 patients with a Quetelet index value >40 who underwent lymph node sampling and there were 69 not sampled. Because only 5% with a Quetelet index value >40 had lymph node metastasis, to obtain significant statistical power to determine whether a survival advantage exists from lymph node sampling, >500 to 1000 women would be needed in each arm. Clearly, there is no statistical power in this study of only 107 women with a Quetelet index value >40. James Fanning, DO Departmentof Obstetricsand Gynecology, Medical College of Ohio, P.O. Box 10008, Toledo, OH 43699-0008 REFERENCE 1. Dawson-Saunders B, Trapp RG. Basic and clinical biostatis- tics. Norwalk (CT): Appleton & Lange, 1990. 6/8/78884 Reply To the Editors: Fanning states that the categorization of patients into three Quetelet index groups is a "common and unacceptable statistical flaw." The reference for this claim is a discussion of the overuse of the X 2 test in comparing two or more groups with respect to the distribution of a numeric outcome variable. With all due respect to this citation, we would point out that it is not a universal rule and that there are many situations in which comparisons among substantively defined groups are useful. In addition, it is widely accepted practice in regression analyses involving a continuous explanatory variable to categorize the variable. This provides infor- mation about the nature of the relationship between the outcome variable and the explanatory variable without making any assumptions about the functional form of the regression equation. This use of indicator variables instead of quantitative variables is described in Neter et al. 1 With respect to the second criticism, we agree that a very large sample size would be required to definitively rule out any survival advantage with lymph node sam- pling. In our sample of 38 women with a Quetelet index >40 who underwent lymph node sampling, only two (4.8%) had positive nodes. The exact two-sided 95% confidence interval for the probability of having positive nodes in this population of women has lower and upper end points of 0.64% and 17.75%, respectively. Thus this sample of size 38 is sufficient only to indicate that the true probability of having positive nodes is unlikely to exceed 17.75%. We continue to maintain that there is no evidence of an adverse effect on survival in obese patients with endometrial cancer who have not had lymph nodes sampled. Further, our data support the conclusion that obese women usually have well-differentiated and less aggressive disease. Barrie Anderson, MD, ~P. Connor, MD, J.L Andrews, MD, J.A. Benda, MD, C.S. Davis, PhD, R.E. BuUer, MD, and f L Sorosky, MD Department of Obstetrics and Gynecology, GynecologicOncology, 4630 JCP, University of Iowa, 200 Hawkins Dr., Iowa City, IA 52242 REFERENCE 1. NeterJ, Wasserman W, Kutner MH. Applied linear statistical models. Homewood (IL): Irwin, 1985. 6/8/78885 Closure of the human fetal ductus arteriosus To the Editors: In a recent issue of the Journal, Hofstadler et al. presented four interesting cases of fetal and neo- natal right ventricular dysfunction attributed to sponta- neous closure of the ductus arteriosus before birth (Hofstadler G, Tulzer G, Altmann R, Schmitt K, Danford D, Huhta JC. Spontaneous closure of the human fetal ductus arteriosus--A cause of fetal congestive heart failure. Am J Obstet Gynecol 1996;174:879-83). The authors stated that in the human fetus spontane- ous closure of the ductus arteriosus unrelated to mater- nal administration of nonsteroidal antiinflammatory agents and glucocorticoids has been reported; they cited four studies. We would like to point out that in two of these cited case reports (Truter et al., 1986; Chaoui et al., 1989) and in No. 3 of their own cases intrauterine ductal closure was associated with maternal administration Of drugs with constrictive effects-on the ductus arteriosus. Prostaglandins, in particular prostaglandin E2, play an important role in maintaining patency of the fetal ductus arteriosus. Maternal administration of agents known to inhibit the synthesis of prostaglandins can cause intra- uterine ductal closure. After birth oxygen appears to induce functional closure characterized by Contraction of the smooth muscle in the wall of the vessel. The cause of intrauterine ductal closure unrelated to administra- tion of drugs with constrictive effects on tile ductus is unknown. In the cases reported by Truter et al. and Chaoui et al., maternal administration of the prostaglandin synthetase inhibitor indomethacin was suspected to be the causative mechanism of intrauterine ductal closure. Constrictive effects of indomethacin are well described in animal and human studies.

Transcript of Reply

Volmne 176, Number 2 Letters 4 9 5 AmJ Obstet Gynecol

statistical design of this retrospective analysis that signif- icantly limits the results and conclusions. First, the au- thors have performed artificial categorization by separat- ing patients into Quetelet index <30, 30 to 40, and >40. This is a common and unacceptable statistical flaw. 1 Because Quetelet index values comprise a continuous numeric scale, patients should be analyzed according to the specific Quetelet index and comparisons should be made along a numeric distribution statistic, such as a t test, rather than artificial categorization and compari- sons with Pearson's X 2.

The second major statistical flaw is that the conclu- sions are not based on the data presented. The last conclusion is that in morbidly obese patients lack of lymph node sampling does not adversely affect survival. In this study there were only 38 patients with a Quetelet index value >40 who underwent lymph node sampling and there were 69 not sampled. Because only 5% with a Quetelet index value >40 had lymph node metastasis, to obtain significant statistical power to determine whether a survival advantage exists from lymph node sampling, >500 to 1000 women would be needed in each arm. Clearly, there is no statistical power in this study of only 107 women with a Quetelet index value >40.

James Fanning, DO Department of Obstetrics and Gynecology, Medical College of Ohio, P.O. Box 10008, Toledo, OH 43699-0008

R E F E R E N C E

1. Dawson-Saunders B, Trapp RG. Basic and clinical biostatis- tics. Norwalk (CT): Appleton & Lange, 1990.

6/8/78884

Reply

To the Editors: Fanning states that the categorization of patients into three Quetelet index groups is a "common and unacceptable statistical flaw." The r e f e r e n c e f o r this claim is a discussion of the overuse of the X 2 test in comparing two o r m o r e groups with respect to the distribution of a numeric outcome variable. With all due respect to this citation, we would point out that it is not a universal rule and that there are many situations in which comparisons among substantively defined groups a r e useful. In addition, it is widely accepted practice in regression analyses involving a continuous explanatory variable to categorize the variable. This provides infor- mation about the nature of the relationship between the outcome variable and the explanatory variable without making any assumptions about the functional form of the regression equation. This use of indicator variables instead of quantitative variables is described in Neter et al. 1

With respect to the second criticism, we agree that a very large sample size would be required to definitively rule out any survival advantage with lymph node sam- pling. In our sample of 38 women with a Quetelet index >40 who underwent lymph node sampling, only two

(4.8%) had positive nodes. The exact two-sided 95% confidence interval for the probability of having positive nodes in this population of women has lower and upper end points of 0.64% and 17.75%, respectively. Thus this sample of size 38 is sufficient only to indicate that the true probability of having positive nodes is unlikely to exceed 17.75%. We continue to maintain that there is no evidence of an adverse effect on survival in obese patients with endometrial cancer who have not had lymph nodes sampled. Further, our data support the conclusion that o b e s e women usually have well-differentiated and less aggressive disease.

Barrie Anderson, MD, ~P. Connor, MD, J.L Andrews, MD, J.A. Benda, MD, C.S. Davis, PhD, R.E. BuUer, MD, and

f L Sorosky, MD Department of Obstetrics and Gynecology, Gynecologic Oncology, 4630 JCP, University of Iowa, 200 Hawkins Dr., Iowa City, IA 52242

REFERENCE 1. NeterJ, Wasserman W, Kutner MH. Applied linear statistical

models. Homewood (IL): Irwin, 1985.

6/8/78885

Closure of the human fetal ductus arteriosus

To the Editors: In a recent issue of the Journal, Hofstadler et al. presented four interesting cases of fetal and neo- natal right ventricular dysfunction attributed to sponta- neous closure of the ductus arteriosus before birth (Hofstadler G, Tulzer G, Altmann R, Schmitt K, Danford D, Huhta JC. Spontaneous closure of the human fetal ductus arteriosus--A cause of fetal congestive heart failure. Am J Obstet Gynecol 1996;174:879-83).

The authors stated that in the human fetus spontane- ous closure of the ductus arteriosus unrelated to mater- nal administration of nonsteroidal antiinflammatory agents and glucocorticoids has been reported; they cited four studies. We would like to point out that in two of these cited case reports (Truter et al., 1986; Chaoui et al., 1989) and in No. 3 of their own cases intrauterine ductal closure was associated with maternal administration Of drugs with constrictive effects-on the ductus arteriosus.

Prostaglandins, in particular prostaglandin E2, play an important role in maintaining patency of the fetal ductus arteriosus. Maternal administration of agents known to inhibit the synthesis of prostaglandins can cause intra- uterine ductal closure. After birth oxygen appears to induce functional closure characterized by Contraction of the smooth muscle in the wall of the vessel. The cause of intrauterine ductal closure unrelated to administra- tion of drugs with constrictive effects on tile ductus is unknown.

In the cases reported by Truter et al. and Chaoui et al., maternal administration of the prostaglandin synthetase inhibitor indomethacin was suspected to be the causative mechanism of intrauterine ductal closure. Constrictive effects of indomethacin are well described in animal and human studies.