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Predictive value and prevalence
Volume 162 l\:umbcr 3
is necessary, as indicated in our calculations. Deep vein thrombosis (DVT) during pregnancy is rare and recurrent pregnancy in these women is even rarer. Heparin dose, at least in some of the patients, may have been suboptimal. Nonetheless the suggestion that the heparin dose was insufficient on the basis that exclusion of superficial thrombophlebitis lowers the frequency in the control groups seems illogical. We agree that the outcome of importance should be DVT and this is why we give the frequency of DVT first in our result section. Clinical diagnosis of DVT is indeed unreliable and that is an established fact. That is why we used only objectively verified DVT in our study. As already stated, the study was retrospective and in the prospective study discussed earlier objective methods for surveillance would be used. But as we wrote in the article, "How should screening take place and how often should it be done?" In approximately 400 pregnant women in a multicenter trial! The quoted abstract does not give any data on how effective heparin prophylaxis is and the safety study (on osteoporosis) is, as far as we can understand, retrospective. The letter seems to end in a contradiction. First, the authors agree with our view that a large randomized trial is necessary to quantitate the risk and evaluate the efficacy of heparin, and then they hope that clinicians still use prophylaxis. Having reread our data and the comments made by Dr. Brill-Edwards et al. we still mean that our conclusions are valid and others have reached similar standpoints. l " Davzd Bergqvist, MD, PhD Lilian Tengborn, MD, PhD Thomas Matzsch, MD Agneta Bergqvist, MD, PhD Ulla Hedner, MD, PhD Department of Surgery Malmo General Hospital Malmo, Sweden S-214 01 REFERENCES 1. de Smiet M, Floyd E, Letsky E. Low risk of recurrent thromboembolism in pregnancy. Br J Hosp Med 1987; 38:264. 2. Dixon]. Pregnancies complicated by previous thromboembolic disease. Br J Hosp Med 1987;37:449-52.
Predictive value and prevalence To the Editors: The following comments refer to the article by Patsner and Mann (The value of preoperative serum CA 125 levels in patients with a pelvic mass. AM J OBsn:T GYNECOL 1988; 159:873-6). The authors found that elevated preoperative serum CA 125 levels are more predictive of malignancy in postmenopausal women than in premenopausal women (0.87 versus 0.67). However, the two super-
Correspondence
871
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w
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PRE - TEST PROBABILITY - PREVALENCE
CJ pre - E3 postmenopausal _
0'tI9I'1ap
Fig. 1. Relationship between pretest probability (prevalence) and posttest probability (positive predictive value) of malignancy according to positive test result of CA 125 in premenopausal women (-.-.) and postmenopausal women (--) (with corresponding 95% confidence ranges) with data of Patsner and Mann. Predictive values for two prevalences (0.41 and 0.62) are indicated.
imposed pretest/posttest probability curves (Fig. 1), which were computed and generated with a test evaluation program l with the use of the data of Patsner and Mann, show that this seeming difference in positive predictive values is mainly because of the difference in prevalence (pretest probability): 0.41 in premenopausal women versus 0.62 in postmenopausal women. On the basis of the same prevalence, the positive predictive values are as follows: 0.67 for premenopausal women and 0.74 for postmenopausal women if prevalence is 0.41; 0.83 for premenopausal women and 0.87 for postmenopausal women if prevalence is 0.62. The difference in test sensitivity or specificity has no significant influence on predictive value as seen by the almost complete overlap of the 95% confidence ranges of the two curves. In summary, the test itself did not work better in postmenopausal women, but the prevalence of malignancy was higher in this group, and therefore the higher positive predictive value! Multiple parallel testing will always improve sensitivity while decreasing specificity, if (as is usually done) conflicting results are classified as positive. 2 This relation means for the prospective studies of the parallel test combination serum CA 125 levels and pelvic ultrasonographic evaluation mentioned in the article's discussion section, that these studies must lead to a decrease of positive predictive value. Rainer G. Kiirzl, MD 1. Frauenklimk der Universitat Milnchen Maistrasse 11 D-8000 Miinchen 2, West Germany
872 Correspondence
March 1990
Am
REFERENCES 1. Abendroth TW, Bongiovanni MB, Krieg AF. A microcomputer program for critical evaluation of diagnostic tests. Arch Pathol Lab Med 1986; 110:952-8. 2. Galen RS, Gambino SR. Beyond normality: the predictive value and efficiency of medical diagnoses. New York: John Wiley & Sons, 1975.
J Obstet Gynecol
ANF
(pgknll 1000
400 Reply To the E ditoTS: Dr. Kiirzl's detailed and thoughtful commentary on my article is greatly appreciated and raises an important point. Clinical investigators often include, and reviewers often insist on, calculations of predictive value of a given test, even though such determinations may be misleading. The main point of my article was that neither the specificity nor sensitivity of the CA 125 assay alone was good enough to allow consistent discrimination of benign from malignant pelvic masses in either premenopausal women or postmenopausal women, although the test is somewhat less misleading in the latter group of patients. Efforts were made to exclude patients known to have those conditions that give false-positive results (e.g., pregnancy, endometriosis) and to exclude patients whose diagnosis of ovarian cancer was virtually unquestionable. The calculation of sensitivity and specificity for CA 125 for the patient population we studied is correct. More to the point, without knowing the true prevalence of the disease (ovarian cancer) in the entire patient population to be screened (those patients with a pelvic mass), it really is not possible to calculate either the negative or positive predictive value of the CA 125 assay in this context. Inclusion of these calculations is interesting but is not correct statistically as, I believe, Dr. Kiirzl points out. Bruce Patsner, MD Division of Gynecology Oncology Watson Clinic P. O. Box 95000 Lakeland, FL 33804-5000
Birth stress Increases fetal atrial natriuretic factor To the Editors: Cheung and Brace nicely showed that in experimental animals fetal hypoxia elevates the concentration of atrial natriuretic factor (ANF) (Cheung CY, Brace RA. Fetal hypoxia elevates plasma atrial natriuretic factor concentration. AM] OBSTET GVNECOL 1988; 159: 12638). To investigate the response of fetal ANF on increased birth stress in man we studied 13 term vaginal deliveries. Seven of these were uncomplicated (I-minute Apgar score = 9), whereas in six cases there were signs of acute fetal distress as revealed by late decelerations in cardiotocography, starting> 15 minutes antepartum; in three of these cases there was meconium in the amniotic fluid. The Apgar scores of the
200 100
40 20
NORMAL
STRESSED
Fig. 1. ANF concentration in umbilical artery (0) and umbilical vein (e) in normal and stressed newborns. Corresponding arterial and venous values are connected with lines. Note logarithmic scale.
stressed infants were 7 or 8. The umbilical cord was doubly clamped within 20 seconds, and blood samples for ANF measurements' were taken from the umbilical artery and vein. In the group with increased birth stress, both arterial (P < 0.02) and venous (P < 0.05) concentrations of ANF were significantly higher than the corresponding values in normal infants. In all cases the ANF concentration in the umbilical artery exceeded that in the umbilical vein (Fig. 1). The results show that the human fetus responds to increased stress by secretion of ANF. It remains to be elucidated whether the primary stimulus for this secretion is hypoxia per se or is a result of other prenatal hormonal alterations! Sture Andersson, MD Mikko Hallman, MD Ilkka Tikkanen, MD Frej FyhrqUlst, MD Departments of Obstetrics and Gynecology, Pediatrics, and Medicine Helsinki University Central Hospital Stenbiickinkatu 11 00290 Helsinki, Finland REFERENCES 1. Tikkanen 1, Fyhrquist F, Metsarinne K, Leidenius R. Plasma atrial natriuretic peptide in cardiac disease and during infusion in healthy volunteers. Lancet 1985;2:66-9.
is necessary, as indicated in our calculations. Deep vein thrombosis (DVT) during pregnancy is rare and recurrent pregnancy in these women is even rarer. Heparin dose, at least in some of the patients, may have been suboptimal. Nonetheless the suggestion that the heparin dose was insufficient on the basis that exclusion of superficial thrombophlebitis lowers the frequency in the control groups seems illogical. We agree that the outcome of importance should be DVT and this is why we give the frequency of DVT first in our result section. Clinical diagnosis of DVT is indeed unreliable and that is an established fact. That is why we used only objectively verified DVT in our study. As already stated, the study was retrospective and in the prospective study discussed earlier objective methods for surveillance would be used. But as we wrote in the article, "How should screening take place and how often should it be done?" In approximately 400 pregnant women in a multicenter trial! The quoted abstract does not give any data on how effective heparin prophylaxis is and the safety study (on osteoporosis) is, as far as we can understand, retrospective. The letter seems to end in a contradiction. First, the authors agree with our view that a large randomized trial is necessary to quantitate the risk and evaluate the efficacy of heparin, and then they hope that clinicians still use prophylaxis. Having reread our data and the comments made by Dr. Brill-Edwards et al. we still mean that our conclusions are valid and others have reached similar standpoints. l " Davzd Bergqvist, MD, PhD Lilian Tengborn, MD, PhD Thomas Matzsch, MD Agneta Bergqvist, MD, PhD Ulla Hedner, MD, PhD Department of Surgery Malmo General Hospital Malmo, Sweden S-214 01 REFERENCES 1. de Smiet M, Floyd E, Letsky E. Low risk of recurrent thromboembolism in pregnancy. Br J Hosp Med 1987; 38:264. 2. Dixon]. Pregnancies complicated by previous thromboembolic disease. Br J Hosp Med 1987;37:449-52.
Predictive value and prevalence To the Editors: The following comments refer to the article by Patsner and Mann (The value of preoperative serum CA 125 levels in patients with a pelvic mass. AM J OBsn:T GYNECOL 1988; 159:873-6). The authors found that elevated preoperative serum CA 125 levels are more predictive of malignancy in postmenopausal women than in premenopausal women (0.87 versus 0.67). However, the two super-
Correspondence
871
• W
)-=>
I-....J
:J~ iiiw
«>
mOb a::0..0
w
I-a:: (/')0..
Ww
t;-> 1--
2§a..
PRE - TEST PROBABILITY - PREVALENCE
CJ pre - E3 postmenopausal _
0'tI9I'1ap
Fig. 1. Relationship between pretest probability (prevalence) and posttest probability (positive predictive value) of malignancy according to positive test result of CA 125 in premenopausal women (-.-.) and postmenopausal women (--) (with corresponding 95% confidence ranges) with data of Patsner and Mann. Predictive values for two prevalences (0.41 and 0.62) are indicated.
imposed pretest/posttest probability curves (Fig. 1), which were computed and generated with a test evaluation program l with the use of the data of Patsner and Mann, show that this seeming difference in positive predictive values is mainly because of the difference in prevalence (pretest probability): 0.41 in premenopausal women versus 0.62 in postmenopausal women. On the basis of the same prevalence, the positive predictive values are as follows: 0.67 for premenopausal women and 0.74 for postmenopausal women if prevalence is 0.41; 0.83 for premenopausal women and 0.87 for postmenopausal women if prevalence is 0.62. The difference in test sensitivity or specificity has no significant influence on predictive value as seen by the almost complete overlap of the 95% confidence ranges of the two curves. In summary, the test itself did not work better in postmenopausal women, but the prevalence of malignancy was higher in this group, and therefore the higher positive predictive value! Multiple parallel testing will always improve sensitivity while decreasing specificity, if (as is usually done) conflicting results are classified as positive. 2 This relation means for the prospective studies of the parallel test combination serum CA 125 levels and pelvic ultrasonographic evaluation mentioned in the article's discussion section, that these studies must lead to a decrease of positive predictive value. Rainer G. Kiirzl, MD 1. Frauenklimk der Universitat Milnchen Maistrasse 11 D-8000 Miinchen 2, West Germany
872 Correspondence
March 1990
Am
REFERENCES 1. Abendroth TW, Bongiovanni MB, Krieg AF. A microcomputer program for critical evaluation of diagnostic tests. Arch Pathol Lab Med 1986; 110:952-8. 2. Galen RS, Gambino SR. Beyond normality: the predictive value and efficiency of medical diagnoses. New York: John Wiley & Sons, 1975.
J Obstet Gynecol
ANF
(pgknll 1000
400 Reply To the E ditoTS: Dr. Kiirzl's detailed and thoughtful commentary on my article is greatly appreciated and raises an important point. Clinical investigators often include, and reviewers often insist on, calculations of predictive value of a given test, even though such determinations may be misleading. The main point of my article was that neither the specificity nor sensitivity of the CA 125 assay alone was good enough to allow consistent discrimination of benign from malignant pelvic masses in either premenopausal women or postmenopausal women, although the test is somewhat less misleading in the latter group of patients. Efforts were made to exclude patients known to have those conditions that give false-positive results (e.g., pregnancy, endometriosis) and to exclude patients whose diagnosis of ovarian cancer was virtually unquestionable. The calculation of sensitivity and specificity for CA 125 for the patient population we studied is correct. More to the point, without knowing the true prevalence of the disease (ovarian cancer) in the entire patient population to be screened (those patients with a pelvic mass), it really is not possible to calculate either the negative or positive predictive value of the CA 125 assay in this context. Inclusion of these calculations is interesting but is not correct statistically as, I believe, Dr. Kiirzl points out. Bruce Patsner, MD Division of Gynecology Oncology Watson Clinic P. O. Box 95000 Lakeland, FL 33804-5000
Birth stress Increases fetal atrial natriuretic factor To the Editors: Cheung and Brace nicely showed that in experimental animals fetal hypoxia elevates the concentration of atrial natriuretic factor (ANF) (Cheung CY, Brace RA. Fetal hypoxia elevates plasma atrial natriuretic factor concentration. AM] OBSTET GVNECOL 1988; 159: 12638). To investigate the response of fetal ANF on increased birth stress in man we studied 13 term vaginal deliveries. Seven of these were uncomplicated (I-minute Apgar score = 9), whereas in six cases there were signs of acute fetal distress as revealed by late decelerations in cardiotocography, starting> 15 minutes antepartum; in three of these cases there was meconium in the amniotic fluid. The Apgar scores of the
200 100
40 20
NORMAL
STRESSED
Fig. 1. ANF concentration in umbilical artery (0) and umbilical vein (e) in normal and stressed newborns. Corresponding arterial and venous values are connected with lines. Note logarithmic scale.
stressed infants were 7 or 8. The umbilical cord was doubly clamped within 20 seconds, and blood samples for ANF measurements' were taken from the umbilical artery and vein. In the group with increased birth stress, both arterial (P < 0.02) and venous (P < 0.05) concentrations of ANF were significantly higher than the corresponding values in normal infants. In all cases the ANF concentration in the umbilical artery exceeded that in the umbilical vein (Fig. 1). The results show that the human fetus responds to increased stress by secretion of ANF. It remains to be elucidated whether the primary stimulus for this secretion is hypoxia per se or is a result of other prenatal hormonal alterations! Sture Andersson, MD Mikko Hallman, MD Ilkka Tikkanen, MD Frej FyhrqUlst, MD Departments of Obstetrics and Gynecology, Pediatrics, and Medicine Helsinki University Central Hospital Stenbiickinkatu 11 00290 Helsinki, Finland REFERENCES 1. Tikkanen 1, Fyhrquist F, Metsarinne K, Leidenius R. Plasma atrial natriuretic peptide in cardiac disease and during infusion in healthy volunteers. Lancet 1985;2:66-9.