- Email: [email protected]
July abstracts
ABSTRACTS
The following abstracts of articles from leading journals and from the ABOG recertification examination have been selected on the basis of their importance to the practice of obstetrics and gynecology.
Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants* BACKGROUND: It is uncertain whether early onset sepsis (occurring within 72 hours of birth) that occurs in very low birth weight infants has changed in character or rate of occurrence since antibiotics have begun to be used more frequently during labor and delivery. METHODS: 5447 infants weighing between 401–1500 g who were born at one of the centers of the Neonatal Research Network between 1998 –2000 who had at least one blood culture in the first three days of life were compared to 7606 similar infants born between 1991–93. RESULTS: The overall rate of early onset sepsis was not different in the two time periods. However, there was a marked reduction in group B streptococcal sepsis in the later birth cohort (5.9/1000 vs 1.7/1000 live births, P ⬍ 0.001). There was an increase in E coli isolates in the later group (3.2/1000 vs 6.8/1000 live births, P⫽0.004). Most (85%) of these E coli isolates in the later group were resistant to ampicillin, and mothers of infants with ampicillin resistant strains were more likely to have received ampicillin during labor. Infants with early onset sepsis were more likely to die than uninfected infants, especially if infected with a gram-negative organism. CONCLUSIONS: Early onset sepsis is a rare but often lethal problem of very low birth weight infants. The change from a predominance of gram positive to gram-negative pathogens should be confirmed by other studies and ongoing surveillance. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, et al. N Engl J Med 2002;347:240 –7 (http://www.nejm.org)
Clinical findings among young women with genital human papillomavirus infection OBJECTIVE: The purpose of this study was to identify clinical signs and symptoms associated with detection of human papillomavirus (HPV) DNA in the female genital tract. STUDY DESIGN: A total of 516 university students (18 to 24 years old) enrolled in a cohort study that included the collection of genital specimens for HPV DNA testing every 4 months for up to 4 years. Reported symptoms and objective clinical findings of women with and without HPV DNA were compared by multivariate analysis. *Modified abstract.
RESULTS: Acute and persisting HPV infections were not associated with discharge, itching, burning, soreness, or fissures. Clinical evidence of genital warts was statistically associated only with HPV types 6 and 11. Detection of any HPV DNA was associated with bacterial vaginosis (BV). Furthermore, a time lag analysis suggests that HPV infection usually precedes detection of BV. CONCLUSION: Most women who acquire genital HPV infection are asymptomatic; some, however, are at increased risk for BV. Mao C, Hughes JP, Kiviat N, Kuypers J, Lee SK, Adam DE, et al. Am J Obstet Gynecol 2003;188:677– 84 (http://www.mosby.com/ajog)
Fetal growth and subsequent risk of breast cancer: Results from long term follow up of Swedish cohort OBJECTIVE: To investigate whether size at birth and rate of fetal growth influence the risk of breast cancer in adulthood. DESIGN: Cohort identified from detailed birth records, with 97% follow up. SETTING: Uppsala Academic Hospital, Sweden. PARTICIPANTS: 5358 singleton females born during 1915–29, alive and traced to the 1960 census. MAIN OUTCOME MEASURES: Incidence of breast cancer before (at age ⬍50 years) and after (ⱖ 50 years) the menopause. RESULTS: Size at birth was positively associated with rates of breast cancer in premenopausal women. In women who weighed ⱖ4000 g at birth rates of breast cancer were 3.5 times (95% confidence interval 1.3 to 9.3) those in women of similar gestational age who weighed ⬍3000 g at birth. Rates in women in the top fifths of the distributions of birth length and head circumference were 3.4 (1.5 to 7.9) and 4.0 (1.6 to 10.0) times those in the lowest fifths (adjusted for gestational age). The effect of birth weight disappeared after adjustment for birth length or head circumference, whereas the effects of birth length and head circumference remained significant after adjustment for birth weight. For a given size at birth, gestational age was inversely associated with risk (P⫽0.03 for linear trend). Adjustment for markers of adult risk factors did not affect these findings. Birth size was not associated with rates of breast cancer in postmenopausal women. CONCLUSIONS: Size at birth, particularly length and head circumference, is associated with risk of breast cancer in women aged ⬍50 years. Fetal growth rate, as measured by birth size adjusted for gestational age, rather than size at birth may be the aetiologically relevant factor in premenopausal breast cancer. McCormack VA, dos Santos Silva I, De Stavola BL, Mohsen R, Leon DA, Lithell HO. BMJ 2003;326(7383):248 (http://bmj.com)
VOL. 102, NO. 1, JULY 2003 © 2003 by The American College of Obstetricians and Gynecologists. Published by Elsevier.
0029-7844/03/$30.00 PII S0029-7844(03)00509-X
193
Cervical cancer and use of hormonal contraceptives: A systematic review BACKGROUND: Human papillomavirus (HPV) is believed to be the most important cause of cervical cancer. Recent studies suggest that long duration use of oral contraceptives increases the risk of cervical cancer in HPV positive women. METHODS: Results from published studies were combined to examine the relationship between invasive and in situ cervical cancer and duration and recency of use of hormonal contraceptives, with particular attention to HPV infection. FINDINGS: 28 eligible studies were identified, together including 12531 women with cervical cancer. Compared with never users of oral contraceptives, the relative risks of cervical cancer increased with increasing duration of use: for durations of approximately less than 5 years, 5–9 years, and 10 or more years, respectively, the summary relative risks were 1.1 (95% CI 1.1–1.2), 1.6 (1.4 –1.7), and 2.2 (1.9 –2.4) for all women; and 0.9 (0.7–1.2), 1.3 (1.0 –1.9), and 2.5 (1.6 –3.9) for HPV positive women. The results were broadly similar for invasive and in situ cervical cancers, for squamous cell and adenocarcinoma, and in studies that adjusted for HPV status, number of sexual partners, cervical screening, smoking, or use of barrier contraceptives. The limited available data suggest that the relative risk of cervical cancer may decrease after use of oral contraceptives ceases. However, study designs varied and there was some heterogeneity between study results. INTERPRETATION: Although long duration use of hormonal contraceptives is associated with an increased risk of cervical cancer, the public health implications of these findings depend largely on the extent to which the observed associations remain long after use of hormonal contraceptives has ceased, and this cannot be evaluated properly from published data. Smith JS, Green J, Berrington de Gonzalez A, Appleby P, Peto J, Plummer M, et al. Lancet 2003;361(9364):1159 – 67 (http://www.thelancet.com)
Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: A randomised controlled trial BACKGROUND: Abnormal vaginal flora and bacterial vaginosis are associated with amplified risks of late miscarriage and spontaneous preterm delivery. We aimed to establish whether antibiotic treatment early in the second trimester might reduce these risks in a general obstetric population. METHODS: We screened 6120 pregnant women attending hospital for their first antenatal visit—who were at 12–22 weeks’ gestation (mean 15.6 weeks)—for bacterial vaginosis or abnormal vaginal flora. We used gram-stained slides of vaginal smears to diagnose abnormal vaginal flora or bacterial vaginosis, in accordance with Nugent’s criteria. We randomly allocated 494 women with one of these signs to receive either clindamycin 300 mg or placebo orally twice daily for 5 days.
194
Abstracts
Primary endpoints were spontaneous preterm delivery (birth ⱖ24 but ⬍37 weeks) and late miscarriage (pregnancy loss ⱖ13 but ⬍24 weeks). Analysis was intention to treat. FINDINGS: Nine women were lost to follow-up or had elective termination. Thus, we analysed 485 women with complete outcome data. Women receiving clindamycin had significantly fewer miscarriages or preterm deliveries (13/244) than did those in the placebo group (38/241; percentage difference 10.4%, 95% CI 5.0 –15.8, p⫽0.0003). Clindamycin also reduced adverse outcomes across the range of abnormal Nugent scores, with maximum effect in women with the highest Nugent score of 10. INTERPRETATION: Treatment of asymptomatic abnormal vaginal flora and bacterial vaginosis with oral clindamycin early in the second trimester significantly reduces the rate of late miscarriage and spontaneous preterm birth in a general obstetric population. Ugwumadu A, Manyonda I, Reid F, Hay P. Lancet 2003;361(9362):983– 8 (http://www.thelancet.com)
Cross sectional study of conventional cervical smear, monolayer cytology, and human papillomavirus DNA testing for cervical cancer screening OBJECTIVES: To compare the sensitivity, specificity, and interobserver reliability of conventional cervical smear tests, monolayer cytology, and human papillomavirus testing for screening for cervical cancer. DESIGN: Cross sectional study in which the three techniques were performed simultaneously with a reference standard (colposcopy and histology). SETTING: Public university and private practices in France, with complete independence from the suppliers. PARTICIPANTS: 828 women referred for colposcopy because of previously detected cytological abnormalities and 1757 women attending for routine smears. MAIN OUTCOME MEASURES: Clinical readings and optimised interpretation (two blind readings followed, if necessary, by consensus). Sensitivity, specificity, and weighted kappa computed for various thresholds of abnormalities. RESULTS: Conventional cervical smear tests were more often satisfactory (91% v 87%) according to the Bethesda system, more reliable (weighted kappa 0.70 v 0.57), and had consistently better sensitivity and specificity than monolayer cytology. These findings applied to clinical readings and optimised interpretations, low and high grade lesions, and populations with low and high incidence of abnormalities. Human papillomavirus testing associated with monolayer cytology, whether systematic or for atypical cells of undetermined significance, performed no better than conventional smear tests. CONCLUSIONS: Monolayer cytology is less reliable and more likely to give false positive and false negative results than conventional cervical smear tests for screening for cervical cancer.
OBSTETRICS & GYNECOLOGY
Coste J, Cochand-Priollet B, de Cremoux P, Le Gales C, Cartier I, Molinie V, et al. BMJ 2003;326(7392):733 (http://bmj.com)
Can ultrasound replace dilation and curettage? A longitudinal evaluation of postmenopausal bleeding and transvaginal sonographic measurement of the endometrium as predictors of endometrial cancer OBJECTIVE: The purpose of this study was to evaluate postmenopausal bleeding and transvaginal sonographic measurement of endometrial thickness as predictors of endometrial cancer and atypical hyperplasia in women whose cases were followed for ⱖ10 years after referral for postmenopausal bleeding. STUDY DESIGN: Women (n ⫽ 394) who had postmenopausal bleeding from November 1987 to October 1990 underwent transvaginal sonographic measurement of endometrial thickness and curettage. It was possible to assess the medical records (regarding recurrence of a postmenopausal bleeding, development of endometrial cancer, and death) in 339 of the 394 women (86%) ⱖ10 years after referral for postmenopausal bleeding. RESULTS: Thirty-nine of the 339 women (11.5%) had endometrial cancer, and 5 women (1.5%) had atypical hyperplasia. The relative risk of endometrial cancer in women who were referred for postmenopausal bleeding was 63.9 (95% CI, 46.0 – 88.8); the corresponding relative risk for endometrial cancer and atypical hyperplasia together was 72.1 (95% CI, 52.8 – 98.5) compared with women of the same age from the general population of the same region of Sweden. No woman with an endometrial thickness of ⱕ4 mm was diagnosed as having endometrial cancer. The relative risk of the development of endometrial cancer in women with an endometrial thickness of ⬎4 mm was 44.5 (95% CI, 6.5–320.1) compared with women with an endometrial thickness of ⱕ4 mm. The reliability of endometrial thickness (cutoff value, ⱕ4 mm) as a diagnostic test for endometrial cancer was assessed: Sensitivity, 100%; specificity, 60%; positive predictive value, 25%; and negative predictive value, 100%. The incidence of endometrial cancer or atypical hyperplasia in women with an intact uterus whose cases had been followed for ⱖ10 years was 5.8% (15/257 women) compared with 22.7% (15/66 women) in women who had ⱕ1 episode of recurrent bleeding. No endometrial cancer was diagnosed in women with a recurrent postmenopausal bleeding who had an endometrial thickness of ⱕ4 mm at the initial scan.
VOL. 102, NO. 1, JULY 2003
CONCLUSION: Postmenopausal bleeding incurs a 64-fold increase risk for endometrial cancer. There was no increased risk of endometrial cancer or atypia in women who did not have recurrent bleeding, whereas women with recurrent bleeding were a high-risk group. No endometrial cancer was missed when endometrial thickness measurement (cutoff value, ⱕ4 mm) was used, even if the women were followed up for ⱕ10 years. We conclude that transvaginal sonographic scanning is an excellent tool for the determination of whether further investigation with curettage or some form of endometrial biopsy is necessary. Gull B, Karlsson B, Milsom I, Granberg S. Am J Obstet Gynecol 2003;188:401– 8 (http://www.mosby.com/ajog)
Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism* BACKGROUND: Standard therapy to prevent recurrent venous thromboembolism includes several months of full-dose (INR ⫽ 2.0 –3.0) continuous anticoagulation. No therapeutic agent has had an acceptable risk-benefit ratio. METHODS: Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation for a median of 6.5 months were randomly assigned to placebo or “low-intensity” (INR ⫽ 1.5–2.0) warfarin therapy. Study participants were followed for recurrent embolic events, major hemorrhage, and death. RESULTS: The trial was terminated early after 508 participants had been followed for a mean of 2.1 years. Among the placeboreceiving participants there were 37 recurrent thromboembolic events (7.2/100 person years) compared with 14 events (2.6/ 1000 person years) in the warfarin-receiving group. This corresponds to a risk reduction of 64% (hazard ratio, 0.36 [95% CI, 0.19 – 0.67], P⬍0.001). Risk reductions were similar for all subgroups. There were major hemorrhages in two participants receiving placebo and five receiving warfarin (P⫽0.25). There were eight deaths in the placebo and four in the warfarin groups. There was a 48% reduction in the composite end-point of recurrent embolism, major hemorrhage, or death. CONCLUSION: Long-term, low-intensity warfarin therapy is highly effective for the prevention of recurrent venous thromboembolism. Ridker PM, Goldhaber SZ, Danielson E, Rosenberg Y, Eby CS, Deitcher SR, et al. N Engl J Med 2003;348:1425–34 (http://www.nejm.org) *Modified abstract.
Abstracts
195
The following abstracts of articles from leading journals and from the ABOG recertification examination have been selected on the basis of their importance to the practice of obstetrics and gynecology.
Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants* BACKGROUND: It is uncertain whether early onset sepsis (occurring within 72 hours of birth) that occurs in very low birth weight infants has changed in character or rate of occurrence since antibiotics have begun to be used more frequently during labor and delivery. METHODS: 5447 infants weighing between 401–1500 g who were born at one of the centers of the Neonatal Research Network between 1998 –2000 who had at least one blood culture in the first three days of life were compared to 7606 similar infants born between 1991–93. RESULTS: The overall rate of early onset sepsis was not different in the two time periods. However, there was a marked reduction in group B streptococcal sepsis in the later birth cohort (5.9/1000 vs 1.7/1000 live births, P ⬍ 0.001). There was an increase in E coli isolates in the later group (3.2/1000 vs 6.8/1000 live births, P⫽0.004). Most (85%) of these E coli isolates in the later group were resistant to ampicillin, and mothers of infants with ampicillin resistant strains were more likely to have received ampicillin during labor. Infants with early onset sepsis were more likely to die than uninfected infants, especially if infected with a gram-negative organism. CONCLUSIONS: Early onset sepsis is a rare but often lethal problem of very low birth weight infants. The change from a predominance of gram positive to gram-negative pathogens should be confirmed by other studies and ongoing surveillance. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, et al. N Engl J Med 2002;347:240 –7 (http://www.nejm.org)
Clinical findings among young women with genital human papillomavirus infection OBJECTIVE: The purpose of this study was to identify clinical signs and symptoms associated with detection of human papillomavirus (HPV) DNA in the female genital tract. STUDY DESIGN: A total of 516 university students (18 to 24 years old) enrolled in a cohort study that included the collection of genital specimens for HPV DNA testing every 4 months for up to 4 years. Reported symptoms and objective clinical findings of women with and without HPV DNA were compared by multivariate analysis. *Modified abstract.
RESULTS: Acute and persisting HPV infections were not associated with discharge, itching, burning, soreness, or fissures. Clinical evidence of genital warts was statistically associated only with HPV types 6 and 11. Detection of any HPV DNA was associated with bacterial vaginosis (BV). Furthermore, a time lag analysis suggests that HPV infection usually precedes detection of BV. CONCLUSION: Most women who acquire genital HPV infection are asymptomatic; some, however, are at increased risk for BV. Mao C, Hughes JP, Kiviat N, Kuypers J, Lee SK, Adam DE, et al. Am J Obstet Gynecol 2003;188:677– 84 (http://www.mosby.com/ajog)
Fetal growth and subsequent risk of breast cancer: Results from long term follow up of Swedish cohort OBJECTIVE: To investigate whether size at birth and rate of fetal growth influence the risk of breast cancer in adulthood. DESIGN: Cohort identified from detailed birth records, with 97% follow up. SETTING: Uppsala Academic Hospital, Sweden. PARTICIPANTS: 5358 singleton females born during 1915–29, alive and traced to the 1960 census. MAIN OUTCOME MEASURES: Incidence of breast cancer before (at age ⬍50 years) and after (ⱖ 50 years) the menopause. RESULTS: Size at birth was positively associated with rates of breast cancer in premenopausal women. In women who weighed ⱖ4000 g at birth rates of breast cancer were 3.5 times (95% confidence interval 1.3 to 9.3) those in women of similar gestational age who weighed ⬍3000 g at birth. Rates in women in the top fifths of the distributions of birth length and head circumference were 3.4 (1.5 to 7.9) and 4.0 (1.6 to 10.0) times those in the lowest fifths (adjusted for gestational age). The effect of birth weight disappeared after adjustment for birth length or head circumference, whereas the effects of birth length and head circumference remained significant after adjustment for birth weight. For a given size at birth, gestational age was inversely associated with risk (P⫽0.03 for linear trend). Adjustment for markers of adult risk factors did not affect these findings. Birth size was not associated with rates of breast cancer in postmenopausal women. CONCLUSIONS: Size at birth, particularly length and head circumference, is associated with risk of breast cancer in women aged ⬍50 years. Fetal growth rate, as measured by birth size adjusted for gestational age, rather than size at birth may be the aetiologically relevant factor in premenopausal breast cancer. McCormack VA, dos Santos Silva I, De Stavola BL, Mohsen R, Leon DA, Lithell HO. BMJ 2003;326(7383):248 (http://bmj.com)
VOL. 102, NO. 1, JULY 2003 © 2003 by The American College of Obstetricians and Gynecologists. Published by Elsevier.
0029-7844/03/$30.00 PII S0029-7844(03)00509-X
193
Cervical cancer and use of hormonal contraceptives: A systematic review BACKGROUND: Human papillomavirus (HPV) is believed to be the most important cause of cervical cancer. Recent studies suggest that long duration use of oral contraceptives increases the risk of cervical cancer in HPV positive women. METHODS: Results from published studies were combined to examine the relationship between invasive and in situ cervical cancer and duration and recency of use of hormonal contraceptives, with particular attention to HPV infection. FINDINGS: 28 eligible studies were identified, together including 12531 women with cervical cancer. Compared with never users of oral contraceptives, the relative risks of cervical cancer increased with increasing duration of use: for durations of approximately less than 5 years, 5–9 years, and 10 or more years, respectively, the summary relative risks were 1.1 (95% CI 1.1–1.2), 1.6 (1.4 –1.7), and 2.2 (1.9 –2.4) for all women; and 0.9 (0.7–1.2), 1.3 (1.0 –1.9), and 2.5 (1.6 –3.9) for HPV positive women. The results were broadly similar for invasive and in situ cervical cancers, for squamous cell and adenocarcinoma, and in studies that adjusted for HPV status, number of sexual partners, cervical screening, smoking, or use of barrier contraceptives. The limited available data suggest that the relative risk of cervical cancer may decrease after use of oral contraceptives ceases. However, study designs varied and there was some heterogeneity between study results. INTERPRETATION: Although long duration use of hormonal contraceptives is associated with an increased risk of cervical cancer, the public health implications of these findings depend largely on the extent to which the observed associations remain long after use of hormonal contraceptives has ceased, and this cannot be evaluated properly from published data. Smith JS, Green J, Berrington de Gonzalez A, Appleby P, Peto J, Plummer M, et al. Lancet 2003;361(9364):1159 – 67 (http://www.thelancet.com)
Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: A randomised controlled trial BACKGROUND: Abnormal vaginal flora and bacterial vaginosis are associated with amplified risks of late miscarriage and spontaneous preterm delivery. We aimed to establish whether antibiotic treatment early in the second trimester might reduce these risks in a general obstetric population. METHODS: We screened 6120 pregnant women attending hospital for their first antenatal visit—who were at 12–22 weeks’ gestation (mean 15.6 weeks)—for bacterial vaginosis or abnormal vaginal flora. We used gram-stained slides of vaginal smears to diagnose abnormal vaginal flora or bacterial vaginosis, in accordance with Nugent’s criteria. We randomly allocated 494 women with one of these signs to receive either clindamycin 300 mg or placebo orally twice daily for 5 days.
194
Abstracts
Primary endpoints were spontaneous preterm delivery (birth ⱖ24 but ⬍37 weeks) and late miscarriage (pregnancy loss ⱖ13 but ⬍24 weeks). Analysis was intention to treat. FINDINGS: Nine women were lost to follow-up or had elective termination. Thus, we analysed 485 women with complete outcome data. Women receiving clindamycin had significantly fewer miscarriages or preterm deliveries (13/244) than did those in the placebo group (38/241; percentage difference 10.4%, 95% CI 5.0 –15.8, p⫽0.0003). Clindamycin also reduced adverse outcomes across the range of abnormal Nugent scores, with maximum effect in women with the highest Nugent score of 10. INTERPRETATION: Treatment of asymptomatic abnormal vaginal flora and bacterial vaginosis with oral clindamycin early in the second trimester significantly reduces the rate of late miscarriage and spontaneous preterm birth in a general obstetric population. Ugwumadu A, Manyonda I, Reid F, Hay P. Lancet 2003;361(9362):983– 8 (http://www.thelancet.com)
Cross sectional study of conventional cervical smear, monolayer cytology, and human papillomavirus DNA testing for cervical cancer screening OBJECTIVES: To compare the sensitivity, specificity, and interobserver reliability of conventional cervical smear tests, monolayer cytology, and human papillomavirus testing for screening for cervical cancer. DESIGN: Cross sectional study in which the three techniques were performed simultaneously with a reference standard (colposcopy and histology). SETTING: Public university and private practices in France, with complete independence from the suppliers. PARTICIPANTS: 828 women referred for colposcopy because of previously detected cytological abnormalities and 1757 women attending for routine smears. MAIN OUTCOME MEASURES: Clinical readings and optimised interpretation (two blind readings followed, if necessary, by consensus). Sensitivity, specificity, and weighted kappa computed for various thresholds of abnormalities. RESULTS: Conventional cervical smear tests were more often satisfactory (91% v 87%) according to the Bethesda system, more reliable (weighted kappa 0.70 v 0.57), and had consistently better sensitivity and specificity than monolayer cytology. These findings applied to clinical readings and optimised interpretations, low and high grade lesions, and populations with low and high incidence of abnormalities. Human papillomavirus testing associated with monolayer cytology, whether systematic or for atypical cells of undetermined significance, performed no better than conventional smear tests. CONCLUSIONS: Monolayer cytology is less reliable and more likely to give false positive and false negative results than conventional cervical smear tests for screening for cervical cancer.
OBSTETRICS & GYNECOLOGY
Coste J, Cochand-Priollet B, de Cremoux P, Le Gales C, Cartier I, Molinie V, et al. BMJ 2003;326(7392):733 (http://bmj.com)
Can ultrasound replace dilation and curettage? A longitudinal evaluation of postmenopausal bleeding and transvaginal sonographic measurement of the endometrium as predictors of endometrial cancer OBJECTIVE: The purpose of this study was to evaluate postmenopausal bleeding and transvaginal sonographic measurement of endometrial thickness as predictors of endometrial cancer and atypical hyperplasia in women whose cases were followed for ⱖ10 years after referral for postmenopausal bleeding. STUDY DESIGN: Women (n ⫽ 394) who had postmenopausal bleeding from November 1987 to October 1990 underwent transvaginal sonographic measurement of endometrial thickness and curettage. It was possible to assess the medical records (regarding recurrence of a postmenopausal bleeding, development of endometrial cancer, and death) in 339 of the 394 women (86%) ⱖ10 years after referral for postmenopausal bleeding. RESULTS: Thirty-nine of the 339 women (11.5%) had endometrial cancer, and 5 women (1.5%) had atypical hyperplasia. The relative risk of endometrial cancer in women who were referred for postmenopausal bleeding was 63.9 (95% CI, 46.0 – 88.8); the corresponding relative risk for endometrial cancer and atypical hyperplasia together was 72.1 (95% CI, 52.8 – 98.5) compared with women of the same age from the general population of the same region of Sweden. No woman with an endometrial thickness of ⱕ4 mm was diagnosed as having endometrial cancer. The relative risk of the development of endometrial cancer in women with an endometrial thickness of ⬎4 mm was 44.5 (95% CI, 6.5–320.1) compared with women with an endometrial thickness of ⱕ4 mm. The reliability of endometrial thickness (cutoff value, ⱕ4 mm) as a diagnostic test for endometrial cancer was assessed: Sensitivity, 100%; specificity, 60%; positive predictive value, 25%; and negative predictive value, 100%. The incidence of endometrial cancer or atypical hyperplasia in women with an intact uterus whose cases had been followed for ⱖ10 years was 5.8% (15/257 women) compared with 22.7% (15/66 women) in women who had ⱕ1 episode of recurrent bleeding. No endometrial cancer was diagnosed in women with a recurrent postmenopausal bleeding who had an endometrial thickness of ⱕ4 mm at the initial scan.
VOL. 102, NO. 1, JULY 2003
CONCLUSION: Postmenopausal bleeding incurs a 64-fold increase risk for endometrial cancer. There was no increased risk of endometrial cancer or atypia in women who did not have recurrent bleeding, whereas women with recurrent bleeding were a high-risk group. No endometrial cancer was missed when endometrial thickness measurement (cutoff value, ⱕ4 mm) was used, even if the women were followed up for ⱕ10 years. We conclude that transvaginal sonographic scanning is an excellent tool for the determination of whether further investigation with curettage or some form of endometrial biopsy is necessary. Gull B, Karlsson B, Milsom I, Granberg S. Am J Obstet Gynecol 2003;188:401– 8 (http://www.mosby.com/ajog)
Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism* BACKGROUND: Standard therapy to prevent recurrent venous thromboembolism includes several months of full-dose (INR ⫽ 2.0 –3.0) continuous anticoagulation. No therapeutic agent has had an acceptable risk-benefit ratio. METHODS: Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation for a median of 6.5 months were randomly assigned to placebo or “low-intensity” (INR ⫽ 1.5–2.0) warfarin therapy. Study participants were followed for recurrent embolic events, major hemorrhage, and death. RESULTS: The trial was terminated early after 508 participants had been followed for a mean of 2.1 years. Among the placeboreceiving participants there were 37 recurrent thromboembolic events (7.2/100 person years) compared with 14 events (2.6/ 1000 person years) in the warfarin-receiving group. This corresponds to a risk reduction of 64% (hazard ratio, 0.36 [95% CI, 0.19 – 0.67], P⬍0.001). Risk reductions were similar for all subgroups. There were major hemorrhages in two participants receiving placebo and five receiving warfarin (P⫽0.25). There were eight deaths in the placebo and four in the warfarin groups. There was a 48% reduction in the composite end-point of recurrent embolism, major hemorrhage, or death. CONCLUSION: Long-term, low-intensity warfarin therapy is highly effective for the prevention of recurrent venous thromboembolism. Ridker PM, Goldhaber SZ, Danielson E, Rosenberg Y, Eby CS, Deitcher SR, et al. N Engl J Med 2003;348:1425–34 (http://www.nejm.org) *Modified abstract.
Abstracts
195